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There is an increased focus on whether mass drug administration (MDA) programmes alone can interrupt the transmission of soil-transmitted helminths (STH).,Mathematical models can be used to model these interventions and are increasingly being implemented to inform investigators about expected trial outcome and the choice of optimum study design.,One key factor is the choice of threshold for detecting elimination.,However, there are currently no thresholds defined for STH regarding breaking transmission.,We develop a simulation of an elimination study, based on the DeWorm3 project, using an individual-based stochastic disease transmission model in conjunction with models of MDA, sampling, diagnostics and the construction of study clusters.,The simulation is then used to analyse the relationship between the study end-point elimination threshold and whether elimination is achieved in the long term within the model.,We analyse the quality of a range of statistics in terms of the positive predictive values (PPV) and how they depend on a range of covariates, including threshold values, baseline prevalence, measurement time point and how clusters are constructed.,End-point infection prevalence performs well in discriminating between villages that achieve interruption of transmission and those that do not, although the quality of the threshold is sensitive to baseline prevalence and threshold value.,Optimal post-treatment prevalence threshold value for determining elimination is in the range 2% or less when the baseline prevalence range is broad.,For multiple clusters of communities, both the probability of elimination and the ability of thresholds to detect it are strongly dependent on the size of the cluster and the size distribution of the constituent communities.,Number of communities in a cluster is a key indicator of probability of elimination and PPV.,Extending the time, post-study endpoint, at which the threshold statistic is measured improves PPV value in discriminating between eliminating clusters and those that bounce back.,The probability of elimination and PPV are very sensitive to baseline prevalence for individual communities.,However, most studies and programmes are constructed on the basis of clusters.,Since elimination occurs within smaller population sub-units, the construction of clusters introduces new sensitivities for elimination threshold values to cluster size and the underlying population structure.,Study simulation offers an opportunity to investigate key sources of sensitivity for elimination studies and programme designs in advance and to tailor interventions to prevailing local or national conditions.

The WHO treatment guidelines for the soil-transmitted helminths (STH) focus on targeting children for the control of morbidity induced by heavy infections.,However, unlike the other STHs, the majority of hookworm infections are harboured by adults.,This untreated burden may have important implications for controlling both hookworm’s morbidity and transmission.,This is particularly significant in the context of the increased interest in investigating STH elimination strategies.,We used a deterministic STH transmission model and parameter estimates derived from field epidemiological studies to evaluate the impact of child-targeted (2-14 year olds) versus community-wide treatment against hookworm in terms of preventing morbidity and the timeframe for breaking transmission.,Furthermore, we investigated how mass treatment may influence the long-term programmatic costs of preventive chemotherapy for hookworm.,The model projected that a large proportion of the overall morbidity due to hookworm was unaffected by the current child-targeted strategy.,Furthermore, driving worm burdens to levels low enough to potentially break transmission was only possible when using community-wide treatment.,Due to these projected reductions in programme duration, it was possible for community-wide treatment to generate cost savings - even if it notably increases the annual distribution costs.,Community-wide treatment is notably more cost-effective for controlling hookworm’s morbidity and transmission than the current child-targeted strategies and could even be cost-saving in many settings in the longer term.,These calculations suggest that it is not optimum to treat using the same treatment strategies as other STH.,Hookworm morbidity and transmission control require community-wide treatment.,The online version of this article (doi:10.1186/s13071-015-1187-5) contains supplementary material, which is available to authorized users.

The RTS,S/AS01 malaria vaccine targets the circumsporozoite protein, inducing antibodies associated with the prevention of Plasmodium falciparum infection.,We assessed the association between anti-circumsporozoite antibody titres and the magnitude and duration of vaccine efficacy using data from a phase 3 trial done between 2009 and 2014.,Using data from 8922 African children aged 5-17 months and 6537 African infants aged 6-12 weeks at first vaccination, we analysed the determinants of immunogenicity after RTS,S/AS01 vaccination with or without a booster dose.,We assessed the association between the incidence of clinical malaria and anti-circumsporozoite antibody titres using a model of anti-circumsporozoite antibody dynamics and the natural acquisition of protective immunity over time.,RTS,S/AS01-induced anti-circumsporozoite antibody titres were greater in children aged 5-17 months than in those aged 6-12 weeks.,Pre-vaccination anti-circumsporozoite titres were associated with lower immunogenicity in children aged 6-12 weeks and higher immunogenicity in those aged 5-17 months.,The immunogenicity of the booster dose was strongly associated with immunogenicity after primary vaccination.,Anti-circumsporozoite titres wane according to a biphasic exponential distribution.,In participants aged 5-17 months, the half-life of the short-lived component of the antibody response was 45 days (95% credible interval 42-48) and that of the long-lived component was 591 days (557-632).,After primary vaccination 12% (11-13) of the response was estimated to be long-lived, rising to 30% (28-32%) after a booster dose.,An anti-circumsporozoite antibody titre of 121 EU/mL (98-153) was estimated to prevent 50% of infections.,Waning anti-circumsporozoite antibody titres predict the duration of efficacy against clinical malaria across different age categories and transmission intensities, and efficacy wanes more rapidly at higher transmission intensity.,Anti-circumsporozoite antibody titres are a surrogate of protection for the magnitude and duration of RTS,S/AS01 efficacy, with or without a booster dose, providing a valuable surrogate of effectiveness for new RTS,S formulations in the age groups considered.,UK Medical Research Council.

Plasmodium falciparum immature gametocytes accumulate in the bone marrow, but their exact location in this tissue remains unclear.,The stage and deposition pattern of gametocytes was analysed on histological sections of a bone marrow sample collected in a patient with subacute P. falciparum malaria.,A majority (89%) of immature stages II to IV gametocytes and a minority (29%) of mature stage V gametocytes were observed in extravascular spaces.,These observations represent a valuable step towards understanding sequestration patterns of P. falciparum gametocytes and may ultimately lead to novel transmission-blocking interventions.

Nested PCR is considered a sensitive and specific method for detecting malaria parasites and is especially useful in epidemiological surveys.,However, the preparation of DNA templates for PCR is often time-consuming and costly.,A simplified PCR method was developed to directly use a small blood filter paper square (2 × 2 mm) as the DNA template after treatment with saponin.,This filter paper-based nested PCR method (FP-PCR) was compared to microscopy and standard nested PCR with DNA extracted by using a Qiagen DNA mini kit from filter paper blood spots of 204 febrile cases.,The FP-PCR technique was further applied to evaluate malaria infections in 1,708 participants from cross-sectional epidemiological surveys conducted in Myanmar and Thailand.,The FP-PCR method had a detection limit of ~0.2 parasites/μL blood, estimated using cultured Plasmodium falciparum parasites.,With 204 field samples, the sensitivity of the FP-PCR method was comparable to that of the standard nested PCR method, which was significantly higher than that of microscopy.,Application of the FP-PCR method in large cross-sectional studies conducted in Myanmar and Thailand detected 1.9% (12/638) and 6.2% (66/1,070) asymptomatic Plasmodium infections, respectively, as compared to the detection rates of 1.3% (8/638) and 0.04% (4/1,070) by microscopy.,This FP-PCR method was much more sensitive than microscopy in detecting Plasmodium infections.,It drastically increased the detection sensitivity of asymptomatic infections in cross-sectional surveys conducted in Thailand and Myanmar, suggesting that this FP-PCR method has a potential for future applications in malaria epidemiology studies.

In the Peruvian Amazon, Plasmodium falciparum and Plasmodium vivax malaria are endemic in rural areas, where microscopy is not available.,Malaria rapid diagnostic tests (RDTs) provide quick and accurate diagnosis.,However, pfhrp2 gene deletions may limit the use of histidine-rich protein-2 (PfHRP2) detecting RDTs.,Further, cross-reactions of P. falciparum with P. vivax-specific test lines and vice versa may impair diagnostic specificity.,Thirteen RDT products were evaluated on 179 prospectively collected malaria positive samples.,Species diagnosis was performed by microscopy and confirmed by PCR.,Pfhrp2 gene deletions were assessed by PCR.,Sensitivity for P. falciparum diagnosis was lower for PfHRP2 compared to P. falciparum-specific Plasmodium lactate dehydrogenase (Pf-pLDH)- detecting RDTs (71.6% vs.,98.7%, p<0.001).,Most (19/21) false negative PfHRP2 results were associated with pfhrp2 gene deletions (25.7% of 74 P. falciparum samples).,Diagnostic sensitivity for P. vivax (101 samples) was excellent, except for two products.,In 10/12 P. vivax-detecting RDT products, cross-reactions with the PfHRP2 or Pf-pLDH line occurred at a median frequency of 2.5% (range 0%-10.9%) of P. vivax samples assessed.,In two RDT products, two and one P. falciparum samples respectively cross-reacted with the Pv-pLDH line.,Two Pf-pLDH/pan-pLDH-detecting RDTs showed excellent sensitivity with few (1.0%) cross-reactions but showed faint Pf-pLDH lines in 24.7% and 38.9% of P. falciparum samples.,PfHRP2-detecting RDTs are not suitable in the Peruvian Amazon due to pfhrp2 gene deletions.,Two Pf-pLDH-detecting RDTs performed excellently and are promising RDTs for this region although faint test lines are of concern.

The epidemiology of malaria in “low-transmission” areas has been underestimated.,Molecular detection methods have revealed higher prevalences of malaria than conventional microscopy or rapid diagnostic tests, but these typically evaluate finger-prick capillary blood samples (∼5 μl) and therefore cannot detect parasite densities of <200/ml.,Their use underestimates true parasite carriage rates.,To characterize the epidemiology of malaria in low-transmission settings and plan elimination strategies, more sensitive quantitative PCR (qPCR) is needed to identify and quantify low-density malaria parasitemias.,A highly sensitive “high-volume” quantitative PCR (qPCR) method based on Plasmodium sp.,18S RNA was adapted for blood sample volumes of ≥250 μl and scaled for high throughput.,The methods were validated by assessment of the analytical sensitivity and specificity, diagnostic sensitivity, and specificity, efficiency, precision, analytical and diagnostic accuracies, limit of detection, root cause analysis of false positives, and robustness.,The high-volume qPCR method based on Plasmodium sp.,18S RNA gave high PCR efficiency of 90 to 105%.,Concentrations of parasite DNA from large volumes of blood gave a consistent analytical detection limit (LOD) of 22 parasites/ml (95% CI, 21.79 to 74.9), which is some 2,500 times more sensitive than conventional microscopy and 50 times more sensitive than currently used PCR methods from filter paper blood spots.,The diagnostic specificity was 99.75%.,Using automated procedures it was possible to process 700 blood samples per week.,A very sensitive and specific high-throughput high-volume qPCR method for the detection of low-density parasitemias (>20 parasites/ml) was developed and validated.

New frontier settlements across the Amazon Basin pose a major challenge for malaria elimination in Brazil.,Here we describe the epidemiology of malaria during the early phases of occupation of farming settlements in Remansinho area, Brazilian Amazonia.,We examine the relative contribution of low-density and asymptomatic parasitemias to the overall Plasmodium vivax burden over a period of declining transmission and discuss potential hurdles for malaria elimination in Remansinho and similar settings.,Eight community-wide cross-sectional surveys, involving 584 subjects, were carried out in Remansinho over 3 years and complemented by active and passive surveillance of febrile illnesses between the surveys.,We used quantitative PCR to detect low-density asexual parasitemias and gametocytemias missed by conventional microscopy.,Mixed-effects multiple logistic regression models were used to characterize independent risk factors for P. vivax infection and disease.,P. vivax prevalence decreased from 23.8% (March-April 2010) to 3.0% (April-May 2013), with no P. falciparum infections diagnosed after March-April 2011.,Although migrants from malaria-free areas were at increased risk of malaria, their odds of having P. vivax infection and disease decreased by 2-3% with each year of residence in Amazonia.,Several findings indicate that low-density and asymptomatic P. vivax parasitemias may complicate residual malaria elimination in Remansinho: (a) the proportion of subpatent infections (i.e. missed by microscopy) increased from 43.8% to 73.1% as P. vivax transmission declined; (b) most (56.6%) P. vivax infections were asymptomatic and 32.8% of them were both subpatent and asymptomatic; (c) asymptomatic parasite carriers accounted for 54.4% of the total P. vivax biomass in the host population; (d) over 90% subpatent and asymptomatic P. vivax had PCR-detectable gametocytemias; and (e) few (17.0%) asymptomatic and subpatent P. vivax infections that were left untreated progressed to clinical disease over 6 weeks of follow-up and became detectable by routine malaria surveillance.

Schistosomiasis is highly prevalent in Yemen, with an estimated 3 million cases, particularly among rural communities.,This community-based study aims to evaluate the knowledge, attitude and practices (KAP) on schistosomiasis among rural communities in Yemen.,A cross-sectional study was carried out among 250 households from ten rural districts in Yemen.,Overall, 400 children were screened for urogenital and intestinal schistosomiasis.,Moreover, parents were interviewed using a pre-tested questionnaire to collect information about the demographic and socioeconomic information and their KAP concerning schistosomiasis.,A total of 127 (31.8 %) children were found to be excreting schistosome eggs in either their urine or faeces (22.5 % S. haematobium and 8.0 % S. mansoni).,Although 92.4 % of the respondents had heard about schistosomiasis, 49.8 %, 68.0 % and 47.2 % had knowledge concerning the transmission, signs and symptoms, and prevention, respectively.,In addition, 77.1 % considered schistosomiasis as harmful while 48.5 % believed that schistosomiasis could be prevented, albeit their practices to prevent infections were still inadequate.,Significant associations between the KAP and age, education, employment status and household monthly income were reported (P < 0.05).,Moreover, a significantly higher level of knowledge was reported among the respondents who had infected children compared to those with no infected family members (P < 0.05).,Multiple logistic regression analysis revealed that the level of education and the history of schistosomiasis were the most important factors associated with the KAP concerning schistosomiasis among this population.,This study reveals that knowledge about the cause, transmission, symptoms and prevention of schistosomiasis among the rural population in Yemen was inadequate, and that this could be a challenging obstacle to the elimination of schistosomiasis in these communities.,Besides the current mass drug administration, school and community-based health education regarding schistosomiasis is imperative among these communities to significantly reduce the transmission and morbidity of schistosomiasis.

The freshwater snail Biomphalaria acts as the intermediate host of Schistosoma mansoni, a globally important human parasite.,Understanding the population structure of intermediate host species can elucidate transmission dynamics and assist in developing appropriate control methods.,We examined levels of population genetic structure and diversity in 29 populations of Biomphalaria choanomphala collected around the shoreline of Lake Victoria in Uganda, Kenya and Tanzania, where S. mansoni is hyper-endemic.,Molecular markers were utilized to estimate the degree to which snail populations are genetically differentiated from one another.,High levels of snail genetic diversity were found coupled with evidence of geographically-determined population structure but low levels of local inbreeding.,The data are consistent with an effect of schistosome infection on population structure of intermediate host snails, but other factors, such as habitat and historical demographic changes, could also be important determinants of the degree of population genetic structure in Biomphalaria choanomphala.,The low stratification of populations and high genetic diversity indicates potentially less local compatibility with intermediate snail populations than previously theorized, and highlights the importance of coordinated parasite control strategies across the region.,The online version of this article (doi:10.1186/s13071-014-0524-4) contains supplementary material, which is available to authorized users.

The extreme genetic diversity of the protozoan Trypanosoma cruzi has been proposed to be associated with the clinical outcomes of the disease it provokes: Chagas disease (CD).,To address this question, we analysed the similarities and differences in the CD pathophysiogenesis caused by different parasite strains.,Using syngeneic mice infected acutely or chronically with 6 distant parasite strains, we integrated simultaneously 66 parameters: parasite tropism (7 parameters), organ and immune responses (local and systemic; 57 parameters), and clinical presentations of CD (2 parameters).,While the parasite genetic background consistently impacts most of these parameters, they remain highly variable, as observed in patients, impeding reliable one-dimensional association with phases, strains, and damage.,However, multi-dimensional statistics overcame this extreme intra-group variability for each individual parameter and revealed some pathophysiological patterns that accurately allow defining (i) the infection phase, (ii) the infecting parasite strains, and (iii) organ damage type and intensity.,Our results demonstrated a greater variability of clinical outcomes and host responses to T. cruzi infection than previously thought, while our multi-parametric analysis defined common pathophysiological patterns linked to clinical outcome of CD, conserved among the genetically diverse infecting strains.

Chagas disease must be treated in all its stages: acute, indeterminate, chronic, and initial and middle determinant chronic, due to the fact that DNA of the parasite can be demonstrated by PCR in chronic cases, where optical microscopy does not detect parasites.,Nifurtimox (NF) and benznidazole (BNZ) are the drugs accepted to treat humans based upon ethical considerations and efficiency.,However, both the drugs produce secondary effects in 30% of the cases, and the treatment must be given for at least 30-60 days.,Other useful drugs are itraconazole and posaconazole.,The latter may be the drug to treat Chagas disease in the future when all the investigations related to it are finished.,At present, there is no criterion of cure for chronic cases since in the majority, the serology remains positive, although it may decrease.,In acute cases, 70% cure with NF and 75% with BNZ is achieved.,In congenital cases, 100% cure is obtained if the treatment is performed during the first year of life.,In chronic acquired cases, 20% cure and 50% improvement of the electrocardiographic changes are obtained with itraconazole.

Although malaria cases have substantially decreased in Southeast Brazil, a significant increase in the number of Plasmodium vivax-like autochthonous human cases has been reported in remote areas of the Atlantic Forest in the past few decades in Rio de Janeiro (RJ) state, including an outbreak during 2015-2016.,The singular clinical and epidemiological aspects in several human cases, and collectively with molecular and genetic data, revealed that they were due to the non-human primate (NHP) parasite Plasmodium simium; however, the understanding of the autochthonous malarial epidemiology in Southeast Brazil can only be acquired by assessing the circulation of NHP Plasmodium in the foci and determining its hosts.,A large sampling effort was carried out in the Atlantic forest of RJ and its bordering states (Minas Gerais, São Paulo, Espírito Santo) for collecting and examining free-living NHPs.,Blood and/or viscera were analyzed for Plasmodium infections via molecular and microscopic techniques.,In total, 146 NHPs of six species, from 30 counties in four states, were tested, of which majority were collected from RJ.,Howler monkeys (Alouatta clamitans) were the only species found infected.,In RJ, 26% of these monkeys tested positive, of which 17% were found to be infected with P. simium.,Importantly, specific single nucleotide polymorphisms-the only available genetic markers that differentiate P. simium from P. vivax-were detected in all P. simium infected A. clamitans despite their geographical origin of malarial foci.,Interestingly, 71% of P. simium infected NHPs were from the coastal slope of a mountain chain (Serra do Mar), where majority of the human cases were found.,Plasmodium brasilianum/malariae was initially detected in 14% and 25% free-living howler monkeys in RJ and in the Espírito Santo (ES) state, respectively.,Moreover, the malarial pigment was detected in the spleen fragments of 50% of a subsample comprising dead howler monkeys in both RJ and ES.,All NHPs were negative for Plasmodium falciparum.,Our data indicate that howler monkeys act as the main reservoir for the Atlantic forest human malarial parasites in RJ and other sites in Southeast Brazil and reinforce its zoonotic characteristics.

Brazil has seen a great decline in malaria and the country is moving towards elimination.,However, for eventual elimination, the control program needs efficient tools in order to monitor malaria exposure and transmission.,In this study, we aimed to evaluate whether seroprevalence to the circumsporozoite protein (CSP) is a good tool for monitoring the exposure to and/or evaluating the burden and distribution of Plasmodium species in the Brazilian Amazon.,Cross-sectional surveys were conducted in a rural area of Porto Velho, Rondônia state.,Parasite infection was detected by microscopy and polymerase chain reaction.,Antibodies to the sporozoite CSP repeats of Plasmodium vivax, P. falciparum, and P. malariae (PvCS, PfCS, and PmCS) were detected using the enzyme-linked immunosorbent assay technique.,Human leukocyte antigen (HLA)-DRB1 and DQB1 genes were typed using Luminex® xMAP® technology.,The prevalence of immunoglobulin G against P. vivax CSP peptide (62%) was higher than P. falciparum (49%) and P. malariae (46%) CSP peptide.,Most of the studied individuals had antibodies to at least one of the three peptides (72%), 34% had antibodies to all three peptides and 28% were non-responders.,Although the majority of the population was not infected at the time of the survey, 74.3% of parasite-negative individuals had antibodies to at least one of the CSPs.,Importantly, among individuals carrying the haplotypes DRB1*04~DQB1*03, there was a significantly higher frequency of PfCS responders, and DRB1*16~DQB1*03 haplotype for PvCS and PfCS responders.,In contrast, HLA-DRB1*01 and HLA-DQB1*05 allelic groups were associated with a lack of antibodies to P. vivax and P. falciparum CSP repeats, and the haplotype DRB1*01~DQB1*05 was also associated with non-responders, including non-responders to P. malariae.,Our results show that in low transmission settings, naturally acquired antibody responses against the CSP repeats of P. vivax, P. falciparum, and P. malariae in a single cross-sectional study may not represent a valuable marker for monitoring recent malaria exposure, especially in an area with a high prevalence of P. vivax.,Furthermore, HLA class II molecules play an important role in antibody response and require further study with a larger sample size.,It will be of interest to consider HLA analysis when using serosurveillance to monitor malaria exposure among genetically diverse populations.,The online version of this article (10.1186/s40249-018-0428-1) contains supplementary material, which is available to authorized users.

Sheep are highly susceptible to infections with Toxoplasma gondii and play a major role in the transmission of toxoplasmosis to humans.,In the present study, 779 serum samples from sheep were collected from Henan province, central China from March 2015 to May 2016, and antibodies to T. gondii were detected by modified agglutination test (MAT).,The overall seroprevalence of T. gondii in sheep was 12.71% (99/779).,The risk factors significantly associated with T. gondii seroprevalence were the geographical origin, age, presence of cats, and the rearing system.,This is the first report of T. gondii infection in sheep in Henan province, central China, and of an association of seropositivity to T. gondii with risk factors.

Toxoplasma gondii infections are prevalent in animals and humans worldwide.,In the present investigation, the seroprevalence of T. gondii in goats was investigated in Hunan province, subtropical China between March 2014 and December 2015.,A total of 1,028 serum samples collected from 14 administrative regions of Hunan province were evaluated by the indirect hemagglutination test (IHAT) for the detection of specific antibodies.,Antibodies to T. gondii were detected in 124 serum samples (12%).,The T. gondii seroprevalence ranged from 1.7% to 19% among different regions in subtropical China, and the differences were statistically significant (p < 0.01).,The results of the present survey indicated that T. gondii infection is prevalent in goats in Hunan, which poses a potential risk for human infection with T. gondii in this province.

Intestinal parasitic infections remain among the most common infectious diseases worldwide.,This study aimed to estimate their prevalence and provide a detailed analysis of geographical distribution of intestinal parasites in the metropolitan region of Rio de Janeiro, considering demographic, socio-economic, and epidemiological contextual factors.,The cross-section survey was conducted among individuals attending the Evandro Chagas National Institute of Infectious Diseases (FIOCRUZ, RJ) during the period from April 2012 to February 2015.,Stool samples were collected and processed by sedimentation, flotation, Kato-Katz, Baermann-Moraes and Graham methods, iron haematoxylin staining and safranin staining.,Of the 3245 individuals analysed, 569 (17.5%) were infected with at least one parasite.,The most common protozoa were Endolimax nana (28.8%), Entamoeba coli (14.8%), Complex Entamoeba histolytica/Entamoeba dispar (13.5%), Blastocystis hominis (12.7%), and Giardia lamblia (8.1%).,Strongyloides stercoralis (4.3%), Schistosoma mansoni (3.3%), Ascaris lumbricoides (1.6%), and hookworms (1.5%) were the most frequent helminths.,There was a high frequency of contamination by protozoa (87%), and multiple infections were observed in 141 participants (24.8%).,A positive association between age (young children) and gender (male) with intestinal parasites was observed.,Geospatial distribution of the detected intestinal parasitic infections was not random or homogeneous, but was influenced by socioeconomic conditions (through the material deprivation index (MDI)).,Participants classified in the highest levels of deprivation had higher risk of having intestinal parasites.,This study provides the first epidemiological information on the prevalence and distribution of intestinal parasitic infections in the Rio de Janeiro metropolitan area.,Intestinal parasites, especially protozoa, are highly prevalent, indicating that parasitic infections are still a serious public health problem.,MDI showed that intestinal parasites were strongly associated with the socioeconomic status of the population, thus making it possible to identify social vulnerable areas.

HIV infection has been modifying both the epidemiology and outcome of parasite infections.,Hence, this study was undertaken to determine the prevalence of Cryptosporidium and other intestinal parasite infections among HIV positives with and without Antiretroviral Treatment(ART) and its association with CD4+ T-cell count.,A cross-sectional study was conducted at Fitche hospital focusing on HIV positives who came to hospital for follow-ups.,A total of 378 HIV positive persons with and without ART participated in the study.,Data on socio-demographic factors and diarrhoea status were obtained by interviewing all 214 with ART and 164 without ART.,Stool samples were collected from all patients and examined for intestinal parasites using direct, formol-ether and modified acid-fast staining techniques.,The prevalence of intestinal parasite infections in this study was significantly higher among HIV positive persons not on ART.,Specifically, the rate of infection with Cryptosporidium species, Blastocystis spp., Giardia lamblia, and Entamoeba histolytica/E. dispar were higher, particularly in those with CD4+ T-cell counts less than 200 cells/µL.,Fifty seven percent of the study participants were on ART.,Out of these 164/378 (43%) of the non-ART study participants were infected with at least one intestinal parasite species.,Significant association was observed between lower CD4+ T-cell count (<200 cells/µL) and the prevalence of Cryptosporidium spp. and Blastocystis spp.,The two parasites were significantly more prevalent in HIV positive non-ART patients.,HIV infection increased the risk of having Cryptosporidium and other intestinal parasites and diarrhoea.,Therefore, raising HIV positive’s immune status and screening for intestinal parasites is important.,This study showed that patients who are taking ART had a lower prevalence of diarrhoea causing parasites and Cryptosporidium suggesting that ART through improvement of immune status of the patients may have contributed to controlling diarrhoea-causing parasites in HIV positive patients.

In 8 malaria-endemic states in India, mixed Plasmodium spp. infections were detected by PCR in 17.4% (265/1,521) of blood samples that microscopy had shown to contain only P. falciparum.,The quality of microscopy must be improved because use of PCR for detection of malaria parasites is limited in rural areas.

Many countries are scaling up malaria interventions towards elimination.,This transition changes demands on malaria diagnostics from diagnosing ill patients to detecting parasites in all carriers including asymptomatic infections and infections with low parasite densities.,Detection methods suitable to local malaria epidemiology must be selected prior to transitioning a malaria control programme to elimination.,A baseline malaria survey conducted in Temotu Province, Solomon Islands in late 2008, as the first step in a provincial malaria elimination programme, provided malaria epidemiology data and an opportunity to assess how well different diagnostic methods performed in this setting.,During the survey, 9,491 blood samples were collected and examined by microscopy for Plasmodium species and density, with a subset also examined by polymerase chain reaction (PCR) and rapid diagnostic tests (RDTs).,The performances of these diagnostic methods were compared.,A total of 256 samples were positive by microscopy, giving a point prevalence of 2.7%.,The species distribution was 17.5% Plasmodium falciparum and 82.4% Plasmodium vivax.,In this low transmission setting, only 17.8% of the P. falciparum and 2.9% of P. vivax infected subjects were febrile (≥38°C) at the time of the survey.,A significant proportion of infections detected by microscopy, 40% and 65.6% for P. falciparum and P. vivax respectively, had parasite density below 100/μL.,There was an age correlation for the proportion of parasite density below 100/μL for P. vivax infections, but not for P. falciparum infections.,PCR detected substantially more infections than microscopy (point prevalence of 8.71%), indicating a large number of subjects had sub-microscopic parasitemia.,The concordance between PCR and microscopy in detecting single species was greater for P. vivax (135/162) compared to P. falciparum (36/118).,The malaria RDT detected the 12 microscopy and PCR positive P. falciparum, but failed to detect 12/13 microscopy and PCR positive P. vivax infections.,Asymptomatic malaria infections and infections with low and sub-microscopic parasite densities are highly prevalent in Temotu province where malaria transmission is low.,This presents a challenge for elimination since the large proportion of the parasite reservoir will not be detected by standard active and passive case detection.,Therefore effective mass screening and treatment campaigns will most likely need more sensitive assays such as a field deployable molecular based assay.

Translational research (TR) is an interdisciplinary branch of the biomedical field that seeks to connect its three supporting pillars: basic research on the bench, the hospital beds and other health system services, and the delivery of products for the well-being and health of the community.,Here, we review the five transition stages of the TR spectrum, registering the lessons learned during > 20 years leading to the first clinical trial designed and performed in Brazil for testing a complementary treatment for Chagas disease (CD): the selenium trial (STCC).,Lessons learned were: (1) to consider all the TR spectrum since the beginning of the project; (2) to start simultaneously animal studies and translation to humans; (3) to ensure a harmonious interaction between clinical and basic research teams; (4) to include MSc and PhD students only in pre-clinical and basic studies (TR0) or vertical clinical studies using retrospective samples and data (TR1); (5) to identify potential suppliers in the national commercial market for a future final treatment since the pre-clinical stage; (6) to keep an international network of experts as permanent advisers on the project.,In the whole process, some perspectives were created: a complementary clinical trial for the opened questions and the construction of a Brazilian clinical CD platform.

Chagas disease is caused by the parasite Trypanosoma cruzi, and it begins with a short acute phase characterized by high parasitemia followed by a life-long chronic phase with scarce parasitism.,Cardiac involvement is the most prominent manifestation, as 30% of infected subjects will develop abnormal ventricular repolarization with myocarditis, fibrosis and cardiomyocyte hypertrophy by undefined mechanisms.,Nevertheless, follow-up studies in chagasic patients, as well as studies with murine models, suggest that the intensity of clinical symptoms and pathophysiological events that occur during the acute phase of disease are associated with the severity of cardiac disease observed during the chronic phase.,In the present study we investigated the role of microRNAs (miRNAs) in the disease progression in response to T. cruzi infection, as alterations in miRNA levels are known to be associated with many cardiovascular disorders.,We screened 641 rodent miRNAs in heart samples of mice during an acute infection with the Colombiana T.cruzi strain and identified multiple miRNAs significantly altered upon infection.,Seventeen miRNAs were found significantly deregulated in all three analyzed time points post infection.,Among these, six miRNAs had their expression correlated with clinical parameters relevant to the disease, such as parasitemia and maximal heart rate-corrected QT (QTc) interval.,Computational analyses identified that the gene targets for these six miRNAs were involved in networks and signaling pathways related to increased ventricular depolarization and repolarization times, important factors for QTc interval prolongation.,The data presented here will guide further studies about the contribution of microRNAs to Chagas heart disease pathogenesis.

The Affordable Medicines Facility-malaria (AMFm) is a pilot program that uses price subsidies to increase access to Artemisinin Combination Therapies (ACTs), currently the most effective malaria treatment.,Recent evidence suggests that availability and affordability of ACTs in retail sector drug shops (where many people treat malaria) has increased under the AMFm, but it is unclear whether household level ACT use has increased.,Household surveys were conducted in two remote regions of Tanzania (Mtwara and Rukwa) in three waves: March 2011, December 2011 and March 2012, corresponding to 3, 13 and 16 months into the AMFm implementation respectively.,Information about suspected malaria episodes including treatment location and medications taken was collected.,Respondents were also asked about antimalarial preferences and perceptions about the availability of these medications.,Significant increases in ACT use, preference and perceived availability were found between Rounds 1 and 3 though not for all measures between Rounds 1 and 2.,ACT use among suspected malaria episodes was 51.1% in March 2011 and increased by 10.9 percentage points by Round 3 (p = .017).,The greatest increase was among retail sector patients, where ACT use increased from 31% in Round 1 to 49% in Round 2 (p = .037) and to 61% (p<.0001) by Round 3.,The fraction of suspected malaria episodes treated in the retail sector increased from 30.2% in Round 1 to 46.7% in Round 3 (p = .0009), mostly due to a decrease in patients who sought no treatment at all.,No significant changes in public sector treatment seeking were found.,The AMFm has led to significant increases in ACT use for suspected malaria, especially in the retail sector.,No evidence is found supporting the concerns that the AMFm would crowd out public sector treatment or neglect patients in remote areas and from low SES groups.

Access to artemisinin-based combination therapy (ACT) remains limited in high malaria-burden countries, and there are concerns that the poorest people are particularly disadvantaged.,This paper presents new evidence on household treatment-seeking behaviour in six African countries.,These data provide a baseline for monitoring interventions to increase ACT coverage, such as the Affordable Medicines Facility for malaria (AMFm).,Nationally representative household surveys were conducted in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia between 2008 and 2010.,Caregivers responded to questions about management of recent fevers in children under five.,Treatment indicators were tabulated across countries, and differences in case management provided by the public versus private sector were examined using chi-square tests.,Logistic regression was used to test for association between socioeconomic status and 1) malaria blood testing, and 2) ACT treatment.,Fever treatment with an ACT is low in Benin (10%), the DRC (5%), Madagascar (3%) and Nigeria (5%), but higher in Uganda (21%) and Zambia (21%).,The wealthiest children are significantly more likely to receive ACT compared to the poorest children in Benin (OR = 2.68, 95% CI = 1.12-6.42); the DRC (OR = 2.18, 95% CI = 1.12-4.24); Madagascar (OR = 5.37, 95% CI = 1.58-18.24); and Nigeria (OR = 6.59, 95% CI = 2.73-15.89).,Most caregivers seek treatment outside of the home, and private sector outlets are commonly the sole external source of treatment (except in Zambia).,However, children treated in the public sector are significantly more likely to receive ACT treatment than those treated in the private sector (except in Madagascar).,Nonetheless, levels of testing and ACT treatment in the public sector are low.,Few caregivers name the national first-line drug as most effective for treating malaria in Madagascar (2%), the DRC (2%), Nigeria (4%) and Benin (10%).,Awareness is higher in Zambia (49%) and Uganda (33%).,Levels of effective fever treatment are low and inequitable in many contexts.,The private sector is frequently accessed however case management practices are relatively poor in comparison with the public sector.,Supporting interventions to inform caregiver demand for ACT and to improve provider behaviour in both the public and private sectors are needed to achieve maximum gains in the context of improved access to effective treatment.

Background.,Malaria remains a major cause of global mortality.,Extracellular heme, released during malaria-induced hemolysis, mediates a number of pathogenic processes associated with vascular and organ injury.,Hemopexin (hpx) facilitates the degradation of extracellular heme.,In this study, we explore the hypothesis that dysregulation of the heme-hpx axis is associated with disease severity, acute kidney injury (AKI), and outcome.,Methods.,Plasma levels of hemin and hpx (at admission, day 3, and day 14) were assessed in children with severe malaria in Jinja, Uganda.,Results.,The ratio of heme to hpx was higher at admission and decreased with recovery (median, 0.043 [interquartile range {IQR}, 0.007-0.239] on day 1, 0.024 [IQR, 0.005-0.126] on day 3, and 0.008 [IQR, 0.002-0.022] on day 14; P < .001).,Ratios of heme to hpx at admission were higher in children with as compared to those without severe anemia (median, 0.124 [IQR, 0.024-0.431] vs 0.016 [IQR, 0.003-0.073]; P < .0001), children with as compared to those without respiratory distress (median, 0.063 [IQR, 0.017-0.413] vs 0.020 [IQR, 0.004-0.124]; P < .01), and children with as opposed to those without stage 3 AKI (median, 0.354 [IQR, 0.123-2.481] vs 0.037 [IQR, 0.005-0.172], P < .01).,The heme to hpx ratio at admission was associated with 6-month mortality (median, 0.148 [IQR, 0.042-0.500] vs 0.039 [IQR, 0.007-0.172]; P = .012).,Conclusions.,The ratio of heme to hpx is associated with disease severity and adverse clinical outcomes in Ugandan children, and dysregulation of the heme axis may contribute to malaria pathogenesis.

Cerebral malaria (CM) is associated with a high mortality rate, and long-term neurocognitive impairment in approximately one third of survivors.,Adjunctive therapies that modify the pathophysiological processes involved in CM may improve outcome over anti-malarial therapy alone.,PPARγ agonists have been reported to have immunomodulatory effects in a variety of disease models.,Here we report that adjunctive therapy with PPARγ agonists improved survival and long-term neurocognitive outcomes in the Plasmodium berghei ANKA experimental model of CM.,Compared to anti-malarial therapy alone, PPARγ adjunctive therapy administered to mice at the onset of CM signs, was associated with reduced endothelial activation, and enhanced expression of the anti-oxidant enzymes SOD-1 and catalase and the neurotrophic factors brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brains of infected mice.,Two months following infection, mice that were treated with anti-malarials alone demonstrated cognitive dysfunction, while mice that received PPARγ adjunctive therapy were completely protected from neurocognitive impairment and from PbA-infection induced brain atrophy.,In humans with P. falciparum malaria, PPARγ therapy was associated with reduced endothelial activation and with induction of neuroprotective pathways, such as BDNF.,These findings provide insight into mechanisms conferring improved survival and preventing neurocognitive injury in CM, and support the evaluation of PPARγ agonists in human CM.

The transmission of malaria by blood transfusion was one of the first recorded incidents of transfusion-transmitted infections (TTIs).,Although the World Health Organization (WHO) recommends that blood for transfusion should be screened for TTIs, malaria screening is not performed in most malaria-endemic countries in sub-Saharan Africa (SSA).,The transfusion of infected red blood cells may lead to severe post-transfusion clinical manifestations of malaria, which could be rapidly fatal.,Ensuring that blood supply in endemic countries is free from malaria is highly problematical, as most of the donors may potentially harbour low levels of malaria parasites.,Pre-transfusion screening within endemic settings has been identified as a cost-effective option for prevention of transfusion-transmitted malaria (TTM).,But currently, there is no screening method that is practical, affordable and suitably sensitive for use by blood banks in SSA.,Even if this method was available, rejection of malaria-positive donors would considerably jeopardize the blood supply and increase morbidity and mortality, especially among pregnant women and children who top the scale of blood transfusion users in SSA.,In this context, the systematic prophylaxis of recipients with anti-malarials could constitute a good alternative, as it prevents any deferral of donor units as well as the occurrence of TTM.,With the on-going programme, namely the Affordable Medicine Facility - Malaria, there is an increase in the availability of low-priced artemisinin-based combination therapy that can be used for systematic prophylaxis.,It appears nonetheless an urgent need to conduct cost-benefit studies in order to evaluate each of the TTM preventive methods.,This approach could permit the design and implementation of an evidence-based measure of TTM prevention in SSA, advocating thereby its widespread use in the region.

Background.,Diagnosis of malaria relies on parasite detection by microscopy or antigen detection; both fail to detect low-density infections.,New tests providing rapid, sensitive diagnosis with minimal need for training would enhance both malaria diagnosis and malaria control activities.,We determined the diagnostic accuracy of a new loop-mediated amplification (LAMP) kit in febrile returned travelers.,Methods.,The kit was evaluated in sequential blood samples from returned travelers sent for pathogen testing to a specialist parasitology laboratory.,Microscopy was performed, and then malaria LAMP was performed using Plasmodium genus and Plasmodium falciparum-specific tests in parallel.,Nested polymerase chain reaction (PCR) was performed on all samples as the reference standard.,Primary outcome measures for diagnostic accuracy were sensitivity and specificity of LAMP results, compared with those of nested PCR.,Results.,A total of 705 samples were tested in the primary analysis.,Sensitivity and specificity were 98.4% and 98.1%, respectively, for the LAMP P. falciparum primers and 97.0% and 99.2%, respectively, for the Plasmodium genus primers.,Post hoc repeat PCR analysis of all 15 tests with discrepant results resolved 4 results in favor of LAMP, suggesting that the primary analysis had underestimated diagnostic accuracy.,Conclusions.,Malaria LAMP had a diagnostic accuracy similar to that of nested PCR, with a greatly reduced time to result, and was superior to expert microscopy.

The extensive use of indoor residual spraying (IRS) and insecticide-treated nets (ITNs) in Africa has contributed to a significant reduction in malaria transmission.,Even so, residual malaria transmission persists in many regions, partly driven by mosquitoes that bite people outdoors.,In areas where Anopheles gambiae s.s. is a dominant vector, most interventions target the reduction of indoor transmission.,The increased use of ITNs/LLINs and IRS has led to the decline of this species.,As a result, less dominant vectors such as Anopheles funestus and Anopheles arabiensis, both also originally indoor vectors but are increasingly biting outdoors, contribute more to residual malaria transmission.,The study reports the investigated community perceptions on malaria and their implications of this for ongoing outdoor malaria transmission and malaria control efforts.,This was a qualitative study conducted in two rural villages and two peri-urban areas located in Kilombero Valley in south-eastern Tanzania. 40 semi-structured in-depth interviews and 8 focus group discussions were conducted with men and women who had children under the age of five.,The Interviews and discussions focused on (1) community knowledge of malaria transmission, and (2) the role of such knowledge on outdoor malaria transmission as a contributing factor to residual malaria transmission.,The use of bed nets for malaria prevention has been stressed in a number of campaigns and malaria prevention programmes.,Most people interviewed believe that there is outdoor malaria transmission since they use interventions while indoors, but they are unaware of changing mosquito host-seeking behaviour.,Participants pointed out that they were frequently bitten by mosquitoes during the evening when outdoors, compared to when they were indoors.,Most participants stay outdoors in the early evening to undertake domestic tasks that cannot be conducted indoors.,House structure, poor ventilation and warm weather conditions were reported to be the main reasons for staying outdoors during the evening.,Participants reported wearing long sleeved clothes, fanning and slapping themselves, using repellents, and burning cow dung and neem tree leaves to chase away mosquitoes.,Community understanding of multiple prevention strategies is crucial given changes in mosquito host seeking behaviour and the increased incidence of outdoor biting.,The current low use of outdoor control measures is attributed largely to limited awareness of outdoor transmission.,Improved community understanding of outdoor malaria transmission is critical: efforts to reduce or eliminate malaria transmission will not be successful if the control of outdoor transmission is not emphasized.

Since 2004, the Tanzanian National Voucher Scheme has increased availability and accessibility of insecticide-treated nets (ITNs) to pregnant women and infants by subsidizing the cost of nets purchased.,From 2008 to 2010, a mass distribution campaign delivered nine million long-lasting insecticidal nets (LLINs) free-of-charge to children under-five years of age in Tanzania mainland.,In 2010 and 2011, a Universal Coverage Campaign (UCC) led by the Ministry of Health and Social Welfare (MoHSW) was implemented to cover all sleeping spaces not yet reached through previous initiatives.,The UCC was coordinated through a unit within the National Malaria Control Programme.,Partners were contracted by the MoHSW to implement different activities in collaboration with local government authorities.,Volunteers registered the number of uncovered sleeping spaces in every household in the country.,On this basis, LLINs were ordered and delivered to village level, where they were issued over a three-day period in each zone (three regions).,Household surveys were conducted in seven districts immediately after the campaign to assess net ownership and use.,The UCC was chiefly financed by the Global Fund to Fight AIDS, Tuberculosis and Malaria with important contributions from the US President’s Malaria Initiative.,A total of 18.2 million LLINs were delivered at an average cost of USD 5.30 per LLIN.,Overall, 83% of the expenses were used for LLIN procurement and delivery and 17% for campaign associated activities.,Preliminary results of the latest Tanzania HIV Malaria Indicator Survey (2011-12) show that household ownership of at least one ITN increased to 91.5%.,ITN use, among children under-five years of age, improved to 72.7% after the campaign.,ITN ownership and use data post-campaign indicated high equity across wealth quintiles.,Close collaboration among the MoHSW, donors, contracted partners, local government authorities and volunteers made it possible to carry out one of the largest LLIN distribution campaigns conducted in Africa to date.,Through the strong increase of ITN use, the recent activities of the national ITN programme will likely result in further decline in child mortality rates in Tanzania, helping to achieve Millennium Development Goals 4 and 6.

Although Plasmodium vivax contributes to almost half of all malaria cases outside Africa, it has been relatively neglected compared to the more deadly P. falciparum.,It is known that P. vivax populations possess high genetic diversity, differing geographically potentially due to different vector species, host genetics and environmental factors.,We analysed the high-quality genomic data for 46 P. vivax isolates spanning 10 countries across 4 continents.,Using population genetic methods we identified hotspots of selection pressure, including the previously reported MRP1 and DHPS genes, both putative drug resistance loci.,Extra copies and deletions in the promoter region of another drug resistance candidate, MDR1 gene, and duplications in the Duffy binding protein gene (PvDBP) potentially involved in erythrocyte invasion, were also identified.,For surveillance applications, continental-informative markers were found in putative drug resistance loci, and we show that organellar polymorphisms could classify P. vivax populations across continents and differentiate between Plasmodia spp.,This study has shown that genomic diversity that lies within and between P. vivax populations can be used to elucidate potential drug resistance and invasion mechanisms, as well as facilitate the molecular barcoding of the parasite for surveillance applications.

Complex malaria infections are defined as those containing more than one genetically distinct lineage of Plasmodium parasite.,Complexity of infection (COI) is a useful parameter to estimate from patient blood samples because it is associated with clinical outcome, epidemiology and disease transmission rate.,This manuscript describes a method for estimating COI using likelihood, called COIL, from a panel of bi-allelic genotyping assays.,COIL assumes that distinct parasite lineages in complex infections are unrelated and that genotyped loci do not exhibit significant linkage disequilibrium.,Using the population minor allele frequency (MAF) of the genotyped loci, COIL uses the binomial distribution to estimate the likelihood of a COI level given the prevalence of observed monomorphic or polymorphic genotypes within each sample.,COIL reliably estimates COI up to a level of three or five with at least 24 or 96 unlinked genotyped loci, respectively, as determined by in silico simulation and empirical validation.,Evaluation of COI levels greater than five in patient samples may require a very large collection of genotype data, making sequencing a more cost-effective approach for evaluating COI under conditions when disease transmission is extremely high.,Performance of the method is positively correlated with the MAF of the genotyped loci.,COI estimates from existing SNP genotype datasets create a more detailed portrait of disease than analyses based simply on the number of polymorphic genotypes observed within samples.,The capacity to reliably estimate COI from a genome-wide panel of SNP genotypes provides a potentially more accurate alternative to methods relying on PCR amplification of a small number of loci for estimating COI.,This approach will also increase the number of applications of SNP genotype data, providing additional motivation to employ SNP barcodes for studies of disease epidemiology or control measure efficacy.,The COIL program is available for download from GitHub, and users may also upload their SNP genotype data to a web interface for simple and efficient determination of sample COI.,The online version of this article (doi:10.1186/1475-2875-14-4) contains supplementary material, which is available to authorized users.

The Government of Ethiopia and its partners have deployed artemisinin-based combination therapies (ACT) since 2004 and long-lasting insecticidal nets (LLINs) since 2005.,Malaria interventions and trends in malaria cases and deaths were assessed at hospitals in malaria transmission areas during 2001-2011.,Regional LLINs distribution records were used to estimate the proportion of the population-at-risk protected by LLINs.,Hospital records were reviewed to estimate ACT availability.,Time-series analysis was applied to data from 41 hospitals in malaria risk areas to assess trends of malaria cases and deaths during pre-intervention (2001-2005) and post-interventions (2006-2011) periods.,The proportion of the population-at-risk potentially protected by LLINs increased to 51% in 2011.,The proportion of facilities with ACTs in stock exceeded 87% during 2006-2011.,Among all ages, confirmed malaria cases in 2011 declined by 66% (95% confidence interval [CI], 44-79%) and SPR by 37% (CI, 20%-51%) compared to the level predicted by pre-intervention trends.,In children under 5 years of age, malaria admissions and deaths fell by 81% (CI, 47%-94%) and 73% (CI, 48%-86%) respectively.,Optimal breakpoint of the trendlines occurred between January and June 2006, consistent with the timing of malaria interventions.,Over the same period, non-malaria cases and deaths either increased or remained unchanged, the number of malaria diagnostic tests performed reflected the decline in malaria cases, and rainfall remained at levels supportive of malaria transmission.,Malaria cases and deaths in Ethiopian hospitals decreased substantially during 2006-2011 in conjunction with scale-up of malaria interventions.,The decrease could not be accounted for by changes in hospital visits, malaria diagnostic testing or rainfall.,However, given the history of variable malaria transmission in Ethiopia, more data would be required to exclude the possibility that the decrease is due to other factors.

Malaria remains one of the leading communicable diseases in Ethiopia.,Early diagnosis combined with prompt treatment is one of the main strategies for malaria prevention and control.,Despite its limitation, Giemsa microscopy is still considered to be the gold standard for malaria diagnosis.,This study aimed to compare the performance of Giemsa microscopy with nested polymerase chain reaction (nPCR) for the diagnosis of malaria in north-west Ethiopia.,A cross sectional study was conducted in public health facilities in North Gondar, from March 2013 to April 2013.,A total number of 297 subjects with suspected malaria were enrolled in the study.,Finger-prick blood samples were collected and examined for Plasmodium parasites using Giemsa microscopy and standard nPCR.,Among the study participants, 61.6% (183/297) patients tested positive for malaria by Giemsa microscopy of which, 72.1% (132/183) and 27.9% (51/183) were diagnosed as Plasmodium falciparum and Plasmodium vivax, respectively.,By nPCR, 73.1% (217/297) were malaria-positive.,Among microscopy-negative samples, 13.1% (39/297) samples turned malaria-positive in nPCR.,In nPCR, the rate of mixed Plasmodium infections was 4.7% (14/297) and 3.03% (9/297) were positive for Plasmodium ovale.,Using nPCR as reference the sensitivity, specificity, positive predictive and negative predictive values of Giemsa microscopy were 82.0%, 93.8%, 97.3% and 65.8%, respectively, with a good agreement (κ = 0.668) to nested PCR.,The sensitivity and specificity of Giemsa microscopy in identifying,P. falciparium infections were 74.0% and 87.4% and 63.2% and 96.5% for P. vivax infections, respectively.,Although Giemsa microscopy remains the gold standard for malaria diagnosis in resource-limited environments, its sensitivity and specificity as compared to nPCR is limited suggesting exploration of novel rapid and simplified molecular techniques for malaria-endemic countries.,A high rate of misclassification and misidentification highlights the importance of adequate training for staff involved in malaria diagnosis.

The rapid and aggressive spread of artemisinin-resistant Plasmodium falciparum carrying the C580Y mutation in the kelch13 gene is a growing threat to malaria elimination in Southeast Asia, but there is no evidence of their spread to other regions.,We conducted cross-sectional surveys in 2016 and 2017 at two clinics in Wewak, Papua New Guinea (PNG) where we identified three infections caused by C580Y mutants among 239 genotyped clinical samples.,One of these mutants exhibited the highest survival rate (6.8%) among all parasites surveyed in ring-stage survival assays (RSA) for artemisinin.,Analyses of kelch13 flanking regions, and comparisons of deep sequencing data from 389 clinical samples from PNG, Indonesian Papua and Western Cambodia, suggested an independent origin of the Wewak C580Y mutation, showing that the mutants possess several distinctive genetic features.,Identity by descent (IBD) showed that multiple portions of the mutants’ genomes share a common origin with parasites found in Indonesian Papua, comprising several mutations within genes previously associated with drug resistance, such as mdr1, ferredoxin, atg18 and pnp.,These findings suggest that a P. falciparum lineage circulating on the island of New Guinea has gradually acquired a complex ensemble of variants, including kelch13 C580Y, which have affected the parasites’ drug sensitivity.,This worrying development reinforces the need for increased surveillance of the evolving parasite populations on the island, to contain the spread of resistance.

Historically, one of the key problems in neglected disease drug discovery has been identifying new and interesting chemotypes.,Phenotypic screening of the malaria parasite, Plasmodium falciparum has yielded almost 30,000 submicromolar hits in recent years.,To make this collection more accessible, a collection of 400 chemotypes has been assembled, termed the Malaria Box.,Half of these compounds were selected based on their drug-like properties and the others as molecular probes.,These can now be requested as a pharmacological test set by malaria biologists, but importantly by groups working on related parasites, as part of a program to make both data and compounds readily available.,In this paper, the analysis and selection methodology and characteristics of the compounds are described.

The mapping of malaria risk has a history stretching back over 100 years.,The last decade, however, has seen dramatic progress in the scope, rigour and sophistication of malaria mapping such that its global distribution is now probably better understood than any other infectious disease.,In this minireview we consider the main factors that have facilitated the recent proliferation of malaria risk mapping efforts and describe the most prominent global-scale endemicity mapping endeavours of recent years.,We describe the diversification of malaria mapping to span a wide range of related metrics of biological and public health importance and consider prospects for the future of the science including its key role in supporting elimination efforts.

Lymphatic filariasis (LF) is one of the neglected tropical diseases targeted for global elimination by 2020 and to guide elimination efforts countries have, in recent years, conducted extensive mapping surveys.,Documenting the past and present distribution of LF and its environmental limits is important for a number of reasons.,Here, we present an initiative to develop a global atlas of LF and present a new global map of the limits of LF transmission.,We undertook a systematic search and assembly of prevalence data worldwide and used a suite of environmental and climatic data and boosted regression trees (BRT) modelling to map the transmission limits of LF.,Data were identified for 66 of the 72 countries currently endemic and for a further 17 countries where LF is no longer endemic.,Our map highlights a restricted and highly heterogeneous distribution in sub-Saharan Africa, with transmission more widespread in West Africa compared to east, central and southern Africa where pockets of transmission occur.,Contemporary transmission occurs across much of south and South-east Asia and the Pacific.,Interestingly, the risk map reflects environmental conditions suitable for LF transmission across Central and South America, including the southern States of America, although active transmission is only known in a few isolated foci.,In countries that have eliminated LF, our predictions of environmental suitability are consistent with historical distribution.,The global distribution of LF is highly heterogeneous and geographically targeted and sustained control will be required to achieve elimination.,This first global map can help evaluate the progress of interventions and guide surveillance activities.,The online version of this article (doi:10.1186/s13071-014-0466-x) contains supplementary material, which is available to authorized users.

Triatomines are hematophagous insects that play an important role as vectors of Trypanosoma cruzi, the causative agent of Chagas disease.,These insects have adapted to multiple blood-feeding sources that can affect relevant aspects of their life-cycle and interactions, thereby influencing parasitic transmission dynamics.,We conducted a characterization of the feeding sources of individuals from the primary circulating triatomine genera in Colombia using amplicon-based next-generation sequencing (NGS).,We used 42 triatomines collected in different departments of Colombia.,DNA was extracted from the gut.,The presence of T. cruzi was identified using real-time PCR, and discrete typing units (DTUs) were determined by conventional PCR.,For blood-feeding source identification, PCR products of the vertebrate 12S rRNA gene were obtained and sequenced by next-generation sequencing (NGS).,Blood-meal sources were inferred using blastn against a curated reference dataset containing the 12S rRNA sequences belonging to vertebrates with a distribution in South America that represent a potential feeding source for triatomine bugs.,Mean and median comparison tests were performed to evaluate differences in triatomine blood-feeding sources, infection state, and geographical regions.,Lastly, the inverse Simpsonʼs diversity index was calculated.,The overall frequency of T. cruzi infection was 83.3%.,TcI was found as the most predominant DTU (65.7%).,A total of 67 feeding sources were detected from the analyses of approximately 7 million reads.,The predominant feeding source found was Homo sapiens (76.8%), followed by birds (10.5%), artiodactyls (4.4%), and non-human primates (3.9%).,There were differences among numerous feeding sources of triatomines of different species.,The diversity of feeding sources also differed depending on the presence of T. cruzi.,To the best of our knowledge, this is the first study to employ amplicon-based NGS of the 12S rRNA gene to depict blood-feeding sources of multiple triatomine species collected in different regions of Colombia.,Our findings report a striking read diversity that has not been reported previously.,This is a powerful approach to unravel transmission dynamics at microgeographical levels.

For the first time, differential attraction of pathogen vectors to vertebrate animals is investigated for novel repellents which when applied to preferred host animals turn them into non-hosts thereby providing a new paradigm for innovative vector control.,For effectively controlling tsetse flies (Glossina spp.), vectors of African trypanosomosis, causing nagana, repellents more powerful than plant derived, from a non-host animal the waterbuck, Kobus ellipsiprymnus defassa, have recently been identified.,Here we investigate these repellents in the field to protect cattle from nagana by making cattle as unattractive as the buck.,To dispense the waterbuck repellents comprising guaiacol, geranylacetone, pentanoic acid and δ-octalactone, (patent application) we developed an innovative collar-mounted release system for individual cattle.,We tested protecting cattle, under natural tsetse challenge, from tsetse transmitted nagana in a large field trial comprising 1,100 cattle with repellent collars in Kenya for 24 months.,The collars provided substantial protection to livestock from trypanosome infection by reducing disease levels >80%.,Protected cattle were healthier, showed significantly reduced disease levels, higher packed cell volume and significantly increased weight.,Collars >60% reduced trypanocide use, 72.7% increase in ownership of oxen per household and enhanced traction power (protected animals ploughed 66% more land than unprotected).,Land under cultivation increased by 73.4%.,Increase in traction power of protected animals reduced by 69.1% acres tilled by hand per household per ploughing season.,Improved food security and household income from very high acceptance of collars (99%) motivated the farmers to form a registered community based organization promoting collars for integrated tsetse control and their commercialization.,Clear demonstration that repellents from un-preferred hosts prevent contact between host and vector, thereby preventing disease transmission: a new paradigm for vector control.,Evidence that deploying water buck repellents converts cattle into non-hosts for tsetse flies-‘cows in waterbuck clothing’.

Despite targeted indoor residual spraying (IRS) over a six-year period and free mass distribution of long-lasting insecticide-treated nets (ITNs), malaria rates in northern Ghana remain high.,Outdoor sleeping and other night-time social, cultural and economic activities that increase exposure to infective mosquito bites are possible contributors.,This study was designed to document these phenomena through direct observation, and to explore the context in which they occur.,During the late dry season months of February and March 2014, study team members carried out continuous household observations from dusk to dawn in one village in Ghana’s Northern Region and one in Upper West Region.,In-depth interviews with health workers and community residents helped supplement observational findings.,Study team members completed observations of 182 individuals across 24 households, 12 households per site.,Between the two sites, they interviewed 14 health workers, six community health volunteers and 28 community residents.,In early evening, nearly all study participants were observed to be outdoors and active.,From 18.00-23.00 hours, socializing, night school, household chores, and small-scale economic activities were common.,All-night funerals, held outdoors and attended by large numbers of community members, were commonly reported and observed.,Outdoor sleeping was frequently documented at both study sites, with 42% of the study population sleeping outdoors at some time during the night.,While interviewees mentioned bed net use as important to malaria prevention, observed use was low for both indoor and outdoor sleeping.,Net access within households was 65%, but only 17% of those with access used a net at any time during the night.,Participants cited heat as the primary barrier and reported higher net use during the rainy season.,Outdoor sleeping and other night-time activities were extensive, and could significantly increase malaria risk.,These findings suggest that indoor-oriented control measures such as ITNs and IRS are insufficient to eliminate malaria in this setting, especially given the low net use observed.,Development and evaluation of complementary outdoor control strategies should be prioritized.,A research agenda is proposed to quantify the relative risk of outdoor night-time activities and test potential vector control interventions that might reduce that risk.

Current front line malaria vector control methods such as indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs), rely upon the preference of many primary vectors to feed and/or rest inside human habitations where they can be targeted with domestically-applied insecticidal products.,We studied the human biting behaviour of the malaria vector Anopheles funestus Giles and the potential malaria vector Anopheles quadriannulatus Theobald in Luangwa valley, south-east Zambia.,Mosquitoes were collected by human landing catch in blocks of houses with either combined use of deltamethrin-based IRS and LLINs or LLINs alone.,Human behaviour data were collected to estimate how much exposure to mosquito bites indoors and outdoors occurred at various times of the night for LLIN users and non-users.,Anopheles funestus and An. quadriannulatus did not show preference to bite either indoors or outdoors: the proportions [95% confidence interval] caught indoors were 0.586 [0.303, 0.821] and 0.624 [0.324, 0.852], respectively.,However, the overwhelming majority of both species were caught at times when most people are indoors.,The proportion of mosquitoes caught at a time when most people are indoors were 0.981 [0.881, 0.997] and 0.897 [0.731, 0.965], respectively, so the proportion of human exposure to both species occuring indoors was high for individuals lacking LLINs (An. funestus: 0.983 and An. quadriannulatus: 0.970, respectively).,While LLIN users were better protected, more than half of their exposure was nevertheless estimated to occur indoors (An. funestus: 0.570 and An. quadriannulatus: 0.584).,The proportion of human exposure to both An. funestus and An. quadriannulatus occuring indoors was high in the area and hence both species might be responsive to further peri-domestic measures if these mosquitoes are susceptible to insecticidal products.

Understanding the spatiotemporal clustering of malaria transmission would help target interventions in settings of low malaria transmission.,The aim of this study was to assess whether malaria infections were clustered in areas with long-lasting insecticidal nets (LLINs) alone, indoor residual spraying (IRS) alone, or a combination of LLINs and IRS interventions, and to determine the risk factors for the observed malaria clustering in southern-central Ethiopia.,A cohort of 34,548 individuals residing in 6,071 households was followed for 121 weeks, from October 2014 to January 2017.,Both active and passive case detection mechanisms were used to identify clinical malaria episodes, and there were no geographic heterogeneity in data collection methods.,Using SaTScan software v 9.4.4, a discrete Poisson model was used to identify high rates of spatial, temporal, and spatiotemporal malaria clustering.,A multilevel logistic regression model was fitted to identify predictors of spatial malaria clustering.,The overall incidence of malaria was 16.5 per 1,000 person-year observations.,Spatial, temporal, and spatiotemporal clustering of malaria was detected in all types of malaria infection (P. falciparum, P. vivax, or mixed).,Spatial clustering was identified in all study arms: for LLIN + IRS arm, a most likely cluster size of 169 cases in 305 households [relative risk (RR) = 4.54, P<0.001]; for LLIN alone arm a cluster size of 88 cases in 103 households (RR = 5.58, P<0.001); for IRS alone arm a cluster size of 58 cases in 50 households (RR = 7.15, P<0.001), and for control arm a cluster size of 147 cases in 377 households (RR = 2.78, P<0.001).,Living 1 km closer to potential vector breeding sites increased the odds of being in spatial clusters by 41.32 fold (adjusted OR = 41.32, 95% CI = 3.79-138.89).,The risk of malaria infection varied significantly between kebeles, within kebeles, and even among households in areas targeted for different types of malaria control interventions in low malaria transmission setting.,The results of this study can be used in planning and implementation of malaria control strategies at micro-geographic scale.,PACT R2014 11000 882128 (8 September 2014).

With more than half of Africa’s population expected to live in urban settlements by 2030, the burden of malaria among urban populations in Africa continues to rise with an increasing number of people at risk of infection.,However, malaria intervention across Africa remains focused on rural, highly endemic communities with far fewer strategic policy directions for the control of malaria in rapidly growing African urban settlements.,The complex and heterogeneous nature of urban malaria requires a better understanding of the spatial and temporal patterns of urban malaria risk in order to design effective urban malaria control programs.,In this study, we use remotely sensed variables and other environmental covariates to examine the predictability of intra-urban variations of malaria infection risk across the rapidly growing city of Dar es Salaam, Tanzania between 2006 and 2014.,High resolution SPOT satellite imagery was used to identify urban environmental factors associated malaria prevalence in Dar es Salaam.,Supervised classification with a random forest classifier was used to develop high resolution land cover classes that were combined with malaria parasite prevalence data to identify environmental factors that influence localized heterogeneity of malaria transmission and develop a high resolution predictive malaria risk map of Dar es Salaam.,Results indicate that the risk of malaria infection varied across the city.,The risk of infection increased away from the city centre with lower parasite prevalence predicted in administrative units in the city centre compared to administrative units in the peri-urban suburbs.,The variation in malaria risk within Dar es Salaam was shown to be influenced by varying environmental factors.,Higher malaria risks were associated with proximity to dense vegetation, inland water and wet/swampy areas while lower risk of infection was predicted in densely built-up areas.,The predictive maps produced can serve as valuable resources for municipal councils aiming to shrink the extents of malaria across cities, target resources for vector control or intensify mosquito and disease surveillance.,The semi-automated modelling process developed can be replicated in other urban areas to identify factors that influence heterogeneity in malaria risk patterns and detect vulnerable zones.,There is a definite need to expand research into the unique epidemiology of malaria transmission in urban areas for focal elimination and sustained control agendas.,The online version of this article (doi:10.1186/s12942-016-0051-y) contains supplementary material, which is available to authorized users.

Trypanosoma cruzi (Kinetoplastea: Trypanosomatidae) infects all tissues of its hosts, which along with humans, include hundreds of mammalian species in the Americas.,The epidemiology of T. cruzi has been changing in that currently the majority of the cases and/or outbreaks of Chagas disease occur by the ingestion of comestibles contaminated by T. cruzi metacyclic forms.,These cases/outbreaks occur in distinct regional scenarios, mainly in the Amazon biome and are related to the local interaction mode of humans with their surroundings, as well as with the overall local ecological peculiarities.,As trypanosomiasis caused by T. cruzi is primarily a zoonosis, understanding the variables that influences its transmission in the wild as well as the role played by the extant fauna in the maintenance of the parasite, is critical in establishing control measures.,Here, we present the results of our studies of T. cruzi infection of free ranging wild mammalian fauna in the five biomes of Brazil, a country of continental dimensions.,From 1992 up to 2017, we examined a total of 6587 free-ranging non-volant wild mammal specimens.,Our studies found that 17% of mammals were seropositive and 8% of all animals displayed positive hemocultures indicative of high parasitemia and, consequently, of infectivity potential.,We observed that opossums, mainly Philander spp. and Didelphis spp., the coati Nasua nasua, the capuchin monkey Sapajus libidinosus and the golden lion tamarin Leontopithecus rosalia, were mammal taxa that demonstrated higher rates of positive hemocultures.,Additionally, Didelphis spp. demonstrated to be a competent bioaccumulator of TcI diversity.,Chiroptera were distinguished for hosting the greatest diversity of species and genotypes of Trypanosoma spp.,Additionally the observation of the higher host range of some Trypanosoma spp., shows the need to reassess the ecology of representatives of the taxon.,Altogether, our results showed that each locality, may display distinct enzootiological and epidemiological scenarios that must be taken into account when it comes to establishing control and/or clarification campaigns of the local population.

Infections with Trypanosoma spp. have been associated with poor health and decreased survival of koalas (Phascolarctos cinereus), particularly in the presence of concurrent pathogens such as Chlamydia and koala retrovirus.,The present study describes the application of a next-generation sequencing (NGS)-based assay to characterise the prevalence and genetic diversity of trypanosome communities in koalas and two native species of ticks (Ixodes holocyclus and I. tasmani) removed from koala hosts.,Among 168 koalas tested, 32.2% (95% CI: 25.2-39.8%) were positive for at least one Trypanosoma sp.,Previously described Trypanosoma spp. from koalas were identified, including T. irwini (32.1%, 95% CI: 25.2-39.8%), T. gilletti (25%, 95% CI: 18.7-32.3%), T. copemani (27.4%, 95% CI: 20.8-34.8%) and T. vegrandis (10.1%, 95% CI: 6.0-15.7%).,Trypanosoma noyesi was detected for the first time in koalas, although at a low prevalence (0.6% 95% CI: 0-3.3%), and a novel species (Trypanosoma sp.,AB-2017) was identified at a prevalence of 4.8% (95% CI: 2.1-9.2%).,Mixed infections with up to five species were present in 27.4% (95% CI: 21-35%) of the koalas, which was significantly higher than the prevalence of single infections 4.8% (95% CI: 2-9%).,Overall, a considerably higher proportion (79.7%) of the Trypanosoma sequences isolated from koala blood samples were identified as T. irwini, suggesting this is the dominant species.,Co-infections involving T. gilletti, T. irwini, T. copemani, T. vegrandis and Trypanosoma sp.,AB-2017 were also detected in ticks, with T. gilletti and T. copemani being the dominant species within the invertebrate hosts.,Direct Sanger sequencing of Trypanosoma 18S rRNA gene amplicons was also performed and results revealed that this method was only able to identify the genotypes with greater amount of reads (according to NGS) within koala samples, which highlights the advantages of NGS in detecting mixed infections.,The present study provides new insights on the natural genetic diversity of Trypanosoma communities infecting koalas and constitutes a benchmark for future clinical and epidemiological studies required to quantify the contribution of trypanosome infections on koala survival rates.

The control and elimination of malaria requires expanded coverage of and access to effective malaria control interventions such as insecticide-treated nets (ITNs), indoor residual spraying (IRS), intermittent preventive treatment (IPT), diagnostic testing and appropriate treatment.,Decisions on how to scale up the coverage of these interventions need to be based on evidence of programme effectiveness, equity and cost-effectiveness.,A systematic review of the published literature on the costs and cost-effectiveness of malaria interventions was undertaken.,All costs and cost-effectiveness ratios were inflated to 2009 USD to allow comparison of the costs and benefits of several different interventions through various delivery channels, across different geographical regions and from varying costing perspectives.,Fifty-five studies of the costs and forty three studies of the cost-effectiveness of malaria interventions were identified, 78% of which were undertaken in sub-Saharan Africa, 18% in Asia and 4% in South America.,The median financial cost of protecting one person for one year was $2.20 (range $0.88-$9.54) for ITNs, $6.70 (range $2.22-$12.85) for IRS, $0.60 (range $0.48-$1.08) for IPT in infants, $4.03 (range $1.25-$11.80) for IPT in children, and $2.06 (range $0.47-$3.36) for IPT in pregnant women.,The median financial cost of diagnosing a case of malaria was $4.32 (range $0.34-$9.34).,The median financial cost of treating an episode of uncomplicated malaria was $5.84 (range $2.36-$23.65) and the median financial cost of treating an episode of severe malaria was $30.26 (range $15.64-$137.87).,Economies of scale were observed in the implementation of ITNs, IRS and IPT, with lower unit costs reported in studies with larger numbers of beneficiaries.,From a provider perspective, the median incremental cost effectiveness ratio per disability adjusted life year averted was $27 (range $8.15-$110) for ITNs, $143 (range $135-$150) for IRS, and $24 (range $1.08-$44.24) for IPT.,A transparent evidence base on the costs and cost-effectiveness of malaria control interventions is provided to inform rational resource allocation by donors and domestic health budgets and the selection of optimal packages of interventions by malaria control programmes.

In the 1990s, the experience of eliminating malaria from Aneityum Island, Vanuatu is often given as evidence for the potential to eliminate malaria in the south-west Pacific.,This experience, however, cannot provide a blueprint for larger islands that represent more complex social and environmental contexts.,Community support was a key contributor to success in Aneityum.,In the context of disappearing disease, obtaining and maintaining community participation in strategies to eliminate malaria in the rest of Tafea Province, Vanuatu will be significantly more challenging.,Nine focus group discussions (FGDs), 12 key informant interviews (KIIs), three transect walks and seven participatory workshops were carried out in three villages across Tanna Island to investigate community perceptions and practices relating to malaria prevention (particularly relating to bed nets); influences on these practices including how malaria is contextualized within community health and disease priorities; and effective avenues for channelling health information.,The primary protection method identified by participants was the use of bed nets, however, the frequency and motivation for their use differed between study villages on the basis of the perceived presence of malaria.,Village, household and personal cleanliness were identified by participants as important for protection against malaria.,Barriers and influences on bed net use included cultural beliefs and practices, travel, gender roles, seasonality of mosquito nuisance and risk perception.,Health care workers and church leaders were reported to have greatest influence on malaria prevention practices.,Participants preferred receiving health information through visiting community health promotion teams, health workers, church leaders and village chiefs.,In low malaria transmission settings, a package for augmenting social capital and sustaining community participation for elimination will be essential and includes: 'sentinel sites' for qualitative monitoring of evolving local socio-cultural, behavioural and practical issues that impact malaria prevention and treatment; mobilizing social networks; intersectoral collaboration; integration of malaria interventions with activities addressing other community health and disease priorities; and targeted implementation of locally appropriate, multi-level, media campaigns that sustain motivation for community participation in malaria elimination.

Western Cambodia is the epicentre of Plasmodium falciparum multidrug resistance and is facing high rates of dihydroartemisinin-piperaquine treatment failures.,Genetic tools to detect the multidrug-resistant parasites are needed.,Artemisinin resistance can be tracked using the K13 molecular marker, but no marker exists for piperaquine resistance.,We aimed to identify genetic markers of piperaquine resistance and study their association with dihydroartemisinin-piperaquine treatment failures.,We obtained blood samples from Cambodian patients infected with P falciparum and treated with dihydroartemisinin-piperaquine.,Patients were followed up for 42 days during the years 2009-15.,We established in-vitro and ex-vivo susceptibility profiles for a subset using piperaquine survival assays.,We determined whole-genome sequences by Illumina paired-reads sequencing, copy number variations by qPCR, RNA concentrations by qRT-PCR, and protein concentrations by immunoblotting.,Fisher’s exact and non-parametric Wilcoxon rank-sum tests were used to identify significant differences in single-nucleotide polymorphisms or copy number variants, respectively, for differential distribution between piperaquine-resistant and piperaquine-sensitive parasite lines.,Whole-genome exon sequence analysis of 31 culture-adapted parasite lines associated amplification of the plasmepsin 2-plasmepsin 3 gene cluster with in-vitro piperaquine resistance.,Ex-vivo piperaquine survival assay profiles of 134 isolates correlated with plasmepsin 2 gene copy number.,In 725 patients treated with dihydroartemisinin-piperaquine, multicopy plasmepsin 2 in the sample collected before treatment was associated with an adjusted hazard ratio (aHR) for treatment failure of 20·4 (95% CI 9·1-45·5, p<0·0001).,Multicopy plasmepsin 2 predicted dihydroartemisinin-piperaquine failures with 0·94 (95% CI 0·88-0·98) sensitivity and 0·77 (0·74-0·81) specificity.,Analysis of samples collected across the country from 2002 to 2015 showed that the geographical and temporal increase of the proportion of multicopy plasmepsin 2 parasites was highly correlated with increasing dihydroartemisinin-piperaquine treatment failure rates (r=0·89 [95% CI 0·77-0·95], p<0·0001, Spearman’s coefficient of rank correlation).,Dihydroartemisinin-piperaquine efficacy at day 42 fell below 90% when the proportion of multicopy plasmepsin 2 parasites exceeded 22%.,Piperaquine resistance in Cambodia is strongly associated with amplification of plasmepsin 2-3, encoding haemoglobin-digesting proteases, regardless of the location.,Multicopy plasmepsin 2 constitutes a surrogate molecular marker to track piperaquine resistance.,A molecular toolkit combining plasmepsin 2 with K13 and mdr1 monitoring should provide timely information for antimalarial treatment and containment policies.,Institut Pasteur in Cambodia, Institut Pasteur Paris, National Institutes of Health, WHO, Agence Nationale de la Recherche, Investissement d’Avenir programme, Laboratoire d’Excellence Integrative “Biology of Emerging Infectious Diseases”.

The declining efficacy of dihydroartemisinin-piperaquine against Plasmodium falciparum in Cambodia, along with increasing numbers of recrudescent cases, suggests resistance to both artemisinin and piperaquine.,Available in vitro piperaquine susceptibility assays do not correlate with treatment outcome.,A novel assay using a pharmacologically relevant piperaquine dose/time exposure was designed and its relevance explored in retrospective and prospective studies.,The piperaquine survival assay (PSA) exposed parasites to 200 nM piperaquine for 48 hours and monitored survival 24 hours later.,The retrospective study tested 32 culture-adapted, C580Y-K13 mutant parasites collected at enrolment from patients treated with a 3-day course of dihydroartemisinin-piperaquine and having presented or not with a recrudescence at day 42 (registered ACTRN12615000793516).,The prospective study assessed ex vivo PSA survival rate alongside K13 polymorphism of isolates collected from patients enrolled in an open-label study with dihydroartemisinin-piperaquine for uncomplicated P. falciparum malaria in Cambodia (registered ACTRN12615000696594).,All parasites from recrudescent cases had in vitro or ex vivo PSA survival rates ≥10 %, a relevant cut-off value for piperaquine-resistance.,Ex vivo PSA survival rates were higher for recrudescent than non-recrudescent cases (39.2 % vs.,0.17 %, P <1 × 10−7).,Artemisinin-resistant K13 mutants with ex vivo PSA survival rates ≥10 % were associated with 32-fold higher risk of recrudescence (95 % CI, 4.5-224; P = 0.0005).,PSA adequately captures the piperaquine resistance/recrudescence phenotype, a mainstay to identify molecular marker(s) and evaluate efficacy of alternative drugs.,Combined ex vivo PSA and K13 genotyping provides a convenient monitor for both artemisinin and piperaquine resistance where dihydroartemisinin-piperaquine is used.,The online version of this article (doi:10.1186/s12916-015-0539-5) contains supplementary material, which is available to authorized users.

Primaquine is effective against the latent liver stage of Plasmodium vivax.,Eliminating the latent liver stage of P. vivax is one of the necessary conditions to achieve the goal of malaria elimination in Lao People’s Democratic Republic (PDR) by 2030.,However, people with glucose-6-phosphate dehydrogenase (G6PD) deficiency are at risk of haemolysis when ingesting primaquine.,The aim of this study was to detect the prevalence of the G6PD Viangchan variant, which is said to be common in Lao PDR and which can result in severe haemolysis in patients exposed to primaquine.,Blood samples were collected from villagers in three malaria endemic provinces: Champasak and Savannakhet in the south, and Phongsaly in the north.,Each blood sample was semi-quantitatively assayed for G6PD enzyme activity using the G6PD Assay Kit-WST Lyophilized (DOJINDO Laboratories, Japan).,Blood samples that were found to be G6PD deficient were sequenced to detect G6PD Viangchan mutation.,In total, 2043 blood samples were collected from Phongsaly (n = 426, 20.9%), Savannakhet (n = 924, 45.2%), and Champasak (n = 693, 33.9%) provinces in Lao PDR from 2016 to 2017.,Of these, 964 (47.2%) were taken from male villagers and 1079 (52.8%) were taken from female villagers.,G6PD Viangchan mutation was not detected in Phongsaly province in this study.,In Savannakhet province, 48 of the 924 samples (45 males, 3 females) had the G6PD Viangchan mutation (n = 48, 5.2%).,In Champasak province, 42 of the 693 samples (18 males, 24 females) had the G6PD Viangchan mutation (n = 42, 6.1%).,G6PD Viangchan variant, which can cause severe haemolysis in the carrier when exposed to primaquine, was detected among 6.1% of the villagers in Champasak and 5.2% in Savannakhet but not in Phongsaly in this study.,G6PD Viangchan variant might be common in the south of Laos but not so in the north.,In the north, other G6PD deficiency variants might be more prevalent.,However, in order not to overlook anyone and ensure a safe primaquine therapy for people living in malaria endemic areas in Lao PDR, G6PD testing is necessary.,The online version of this article (10.1186/s12936-019-2715-0) contains supplementary material, which is available to authorized users.

A large fraction of Plasmodium infections do not cause clinical signs and symptoms of disease and persist at densities in blood that are not detectable by microscopy or rapid diagnostic tests.,These infections may be critical as a transmission reservoir in areas of low malaria endemicity.,Understanding the epidemiology of these infections would be helpful for malaria elimination.,A cross-sectional survey was conducted in Thapangthong and Nong Districts of Savannakhet Province, Lao PDR, to determine the prevalence of parasitaemia.,A total of 888 blood samples were collected from afebrile volunteers aged ≥15 years in 18 villages during March and July 2015.,Plasmodium infections were diagnosed by rapid diagnostic tests (RDT) and high volume, ultra-sensitive quantitative polymerase chain reaction (uPCR).,uPCR detected Plasmodium infections in 175 of 888 samples (20 %).,The species distribution was Plasmodiumfalciparum 3.6 % (32/888), Plasmodium vivax 11.1 % (99/888), mixed infections with P. falciparum and P. vivax 1.6 % (14/888) and Plasmodium of undetermined species 3.4 % (30/888).,RDT identified only 2 % (18/888) positive cases.,Using uPCR as reference, the sensitivity and specificity of RDTs were 28 and 100 %, respectively, in detecting P. falciparum infections, and 3 and 99 % in detecting asymptomatic P. vivax infections.,The K13 kelch propeller domain C580Y mutation, associated with reduced susceptibility to artemisinin derivatives, was found in 75 % (12/18) of P. falciparum isolates from Thapangthong and in 7 % (2/28) from Nong (p < 0.001).,In a multivariate analysis, males were more likely to have P. vivax infections [adjusted odds ratio (aOR) 4.76 (95 % CI 2.84-8.00)] while older villagers were at lower risk for parasitaemia [aOR for increasing age 0.98 (95 % CI 0.96-0.99)].,There is a high prevalence of asymptomatic Plasmodium infections in southern Savannakhet.,Artemisinin-resistant P. falciparum strains form an increasing proportion of the parasite population in Thapangthong District and are already present in the more remote Nong District.,This worrying trend has wider implications for Laos and could reverse the gains achieved by the successful control of malaria in Laos and the Greater Mekong Sub-region (GMS).,Rapid elimination of P. falciparum has to be a top priority in Laos as well as in the wider GMS.

A national HIV/AIDS and malaria parasitological survey was carried out in Tanzania in 2007-2008.,In this study the parasitological data were analyzed: i) to identify climatic/environmental, socio-economic and interventions factors associated with child malaria risk and ii) to produce a contemporary, high spatial resolution parasitaemia risk map of the country.,Bayesian geostatistical models were fitted to assess the association between parasitaemia risk and its determinants.,Bayesian kriging was employed to predict malaria risk at unsampled locations across Tanzania and to obtain the uncertainty associated with the predictions.,Markov chain Monte Carlo (MCMC) simulation methods were employed for model fit and prediction.,Parasitaemia risk estimates were linked to population data and the number of infected children at province level was calculated.,Model validation indicated a high predictive ability of the geostatistical model, with 60.00% of the test locations within the 95% credible interval.,The results indicate that older children are significantly more likely to test positive for malaria compared with younger children and living in urban areas and better-off households reduces the risk of infection.,However, none of the environmental and climatic proxies or the intervention measures were significantly associated with the risk of parasitaemia.,Low levels of malaria prevalence were estimated for Zanzibar island.,The population-adjusted prevalence ranges from in Kaskazini province (Zanzibar island) to in Mtwara region.,The pattern of predicted malaria risk is similar with the previous maps based on historical data, although the estimates are lower.,The predicted maps could be used by decision-makers to allocate resources and target interventions in the regions with highest burden of malaria in order to reduce the disease transmission in the country.

The Zambia Malaria Indicator Survey (ZMIS) of 2006 was the first nation-wide malaria survey, which combined parasitological data with other malaria indicators such as net use, indoor residual spraying and household related aspects.,The survey was carried out by the Zambian Ministry of Health and partners with the objective of estimating the coverage of interventions and malaria related burden in children less than five years.,In this study, the ZMIS data were analysed in order (i) to estimate an empirical high-resolution parasitological risk map in the country and (ii) to assess the relation between malaria interventions and parasitaemia risk after adjusting for environmental and socio-economic confounders.,The parasitological risk was predicted from Bayesian geostatistical and spatially independent models relating parasitaemia risk and environmental/climatic predictors of malaria.,A number of models were fitted to capture the (potential) non-linearity in the malaria-environment relation and to identify the elapsing time between environmental effects and parasitaemia risk.,These models included covariates (a) in categorical scales and (b) in penalized and basis splines terms.,Different model validation methods were used to identify the best fitting model.,Model-based risk predictions at unobserved locations were obtained via Bayesian predictive distributions for the best fitting model.,Model validation indicated that linear environmental predictors were able to fit the data as well as or even better than more complex non-linear terms and that the data do not support spatial dependence.,Overall the averaged population-adjusted parasitaemia risk was 20.0% in children less than five years with the highest risk predicted in the northern (38.3%) province.,The odds of parasitaemia in children living in a household with at least one bed net decreases by 40% (CI: 12%, 61%) compared to those without bed nets.,The map of parasitaemia risk together with the prediction error and the population at risk give an important overview of the malaria situation in Zambia.,These maps can assist to achieve better resource allocation, health management and to target additional interventions to reduce the burden of malaria in Zambia significantly.,Repeated surveys will enable the evaluation of the effectiveness of on-going interventions.

The in utero environment profoundly impacts childhood neurodevelopment and behaviour.,A substantial proportion of pregnancies in Africa are at risk of malaria in pregnancy (MIP) however the impact of in utero exposure to MIP on fetal neurodevelopment is unknown.,Complement activation, in particular C5a, may contribute to neuropathology and adverse outcomes during MIP.,We used an experimental model of MIP and standardized neurocognitive testing, MRI, micro-CT and HPLC analysis of neurotransmitter levels, to test the hypothesis that in utero exposure to malaria alters neurodevelopment through a C5a-C5aR dependent pathway.,We show that malaria-exposed offspring have persistent neurocognitive deficits in memory and affective-like behaviour compared to unexposed controls.,These deficits were associated with reduced regional brain levels of major biogenic amines and BDNF that were rescued by disruption of C5a-C5aR signaling using genetic and functional approaches.,Our results demonstrate that experimental MIP induces neurocognitive deficits in offspring and suggest novel targets for intervention.

Pentoxifylline (PTX) affects many processes that may contribute to the pathogenesis of severe malaria and it has been shown to reduce the duration of coma in children with cerebral malaria.,This pilot study was performed to assess pharmacokinetics, safety and efficacy of PTX in African children with cerebral malaria.,Ten children admitted to the high dependency unit of the Kilifi District Hospital in Kenya with cerebral malaria (Blantyre coma score of 2 or less) received quinine plus a continuous infusion of 10 mg/kg/24 hours PTX for 72 hours.,Five children were recruited as controls and received normal saline instead of PTX.,Plasma samples were taken for PTX and tumour necrosis factor (TNF) levels.,Blantyre Coma Score, parasitemia, hematology and vital signs were assessed 4 hourly.,One child (20%) in the control group died, compared to four children (40%) in the PTX group.,This difference was not significant (p = 0.60).,Laboratory parameters and clinical data were comparable between groups.,TNF levels were lower in children receiving PTX.,The small sample size does not permit definitive conclusions, but the mortality rate was unexpectedly high in the PTX group.

Humans are susceptible to over 1400 pathogens.,Co-infection by multiple pathogens is common, and can result in a range of neutral, facilitative, or antagonistic interactions within the host.,Soil-transmitted helminths (STH) are powerful immunomodulators, but evidence of the effect of STH infection on the direction and magnitude of concurrent enteric microparasite infections is mixed.,We collected fecal samples from 891 randomly selected children and adults in rural Laos.,Samples were analyzed for 5 STH species, 6 viruses, 9 bacteria, and 5 protozoa using a quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay.,We utilized logistic regression, controlling for demographics and household water, sanitation, and hygiene access, to examine the effect of STH infection on concurrent viral, bacterial, and protozoal infection.,We found that STH infection was associated with lower odds of concurrent viral infection [odds ratio (OR): 0.48, 95% confidence interval (CI): 0.28-0.83], but higher odds of concurrent bacterial infections (OR: 1.81, 95% CI: 1.06-3.07) and concurrent protozoal infections (OR: 1.50, 95% CI: 0.95-2.37).,Trends were consistent across STH species.,The impact of STH on odds of concurrent microparasite co-infection may differ by microparasite taxa, whereby STH infection was negatively associated with viral infections but positively associated with bacterial and protozoal infections.,Results suggest that efforts to reduce STH through preventive chemotherapy could have a spillover effect on microparasite infections, though the extent of this impact requires additional study.,The associations between STH and concurrent microparasite infection may reflect a reverse effect due to the cross-sectional study design.,Additional research is needed to elucidate the exact mechanism of the immunomodulatory effects of STH on concurrent enteric microparasite infection.,The online version of this article (10.1186/s13071-019-3471-2) contains supplementary material, which is available to authorized users.

We investigated the prevalence, risk factors, and clinical manifestations of schistosomiasis in White Nile State, Sudan, to determine the local characteristics of schistosomiasis in the White Nile River basin.,Urine and stool samples were collected from 338 students (176 boys, 162 girls) at three primary schools and were examined using the urine filtration method and the Kato-Katz technique, respectively.,Of the students, 200 were interviewed using a semi-structured questionnaire to assess water-contact patterns and health conditions related with urinary schistosomiasis.,Of the 338 students, egg-positive rates for S. haematobium and S. mansoni were 45.0% and 5.9%, respectively, and 4.4% were mixed.,The intensities of S. haematobium and S. mansoni infection were 1.091 ± 0.744 log EP10 (eggs per 10 mL of urine, mean ± SD = 57 ± 172 EP10) and 1.787 ± 0.844 log EPG (eggs per gram of stool, mean ± SD = 156 ± 176 EPG), respectively.,The prevalence and intensity of S. haematobium infection differed significantly among the three schools, but not by gender or age.,Urinary schistosomiasis was significantly associated with the frequencies of contaminated water contact, taking baths, swimming, and wading the stream; however, frequencies of these events were not significantly correlated with infection intensity.,Self-reported hematuria and dysuria also correlated significantly with urinary schistosomiasis.,The overall prevalence of schistosomiasis, especially urinary schistosomiasis, is high in the White Nile River basin, Sudan, and is closely associated with frequencies of water contact, taking baths, swimming, and wading the stream.,We strongly recommend implementation of an integrated schistosomiasis control program in this area.

The World Health Organization (WHO) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common.,As the intervention is often claimed to have important health, nutrition, and societal effects beyond the removal of worms, we critically evaluated the evidence on benefits.,To summarize the effects of giving deworming drugs to children to treat soil‐transmitted helminths on weight, haemoglobin, and cognition; and the evidence of impact on physical well‐being, school attendance, school performance, and mortality.,We searched the Cochrane Infectious Diseases Group Specialized Register (14 April 2015); Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library (2015, Issue 4); MEDLINE (2000 to 14 April 2015); EMBASE (2000 to 14 April 2015); LILACS (2000 to 14 April 2015); the metaRegister of Controlled Trials (mRCT); and reference lists, and registers of ongoing and completed trials up to 14 April 2015.,We included randomized controlled trials (RCTs) and quasi‐RCTs comparing deworming drugs for soil‐transmitted helminths with placebo or no treatment in children aged 16 years or less, reporting on weight, haemoglobin, and formal tests of intellectual development.,We also sought data on school attendance, school performance, and mortality.,We included trials that combined health education with deworming programmes.,At least two review authors independently assessed the trials, evaluated risk of bias, and extracted data.,We analysed continuous data using the mean difference (MD) with 95% confidence intervals (CIs).,Where data were missing, we contacted trial authors.,We used outcomes at time of longest follow‐up.,The evidence quality was assessed using GRADE.,This edition of the Cochrane Review adds the DEVTA trial from India, and draws on an independent analytical replication of a trial from Kenya.,We identified 45 trials, including nine cluster‐RCTs, that met the inclusion criteria.,One trial evaluating mortality included over one million children, and the remaining 44 trials included a total of 67,672 participants.,Eight trials were in children known to be infected, and 37 trials were carried out in endemic areas, including areas of high (15 trials), moderate (12 trials), and low prevalence (10 trials).,Treating children known to be infected,Treating children known to be infected with a single dose of deworming drugs (selected by screening, or living in areas where all children are infected) may increase weight gain over the next one to six months (627 participants, five trials, low quality evidence).,The effect size varied across trials from an additional 0.2 kg gain to 1.3 kg.,There is currently insufficient evidence to know whether treatment has additional effects on haemoglobin (247 participants, two trials, very low quality evidence); school attendance (0 trials); cognitive functioning (103 participants, two trials, very low quality evidence), or physical well‐being (280 participants, three trials, very low quality evidence).,Community deworming programmes,Treating all children living in endemic areas with a dose of deworming drugs probably has little or no effect on average weight gain (MD 0.04 kg less, 95% CI 0.11 kg less to 0.04 kg more; trials 2719 participants, seven trials, moderate quality evidence), even in settings with high prevalence of infection (290 participants, two trials).,A single dose also probably has no effect on average haemoglobin (MD 0.06 g/dL, 95% CI ‐0.05 lower to 0.17 higher; 1005 participants, three trials, moderate quality evidence), or average cognition (1361 participants, two trials, low quality evidence).,Similiarly, regularly treating all children in endemic areas with deworming drugs, given every three to six months, may have little or no effect on average weight gain (MD 0.08 kg, 95% CI 0.11 kg less to 0.27 kg more; 38,392 participants, 10 trials, low quality evidence).,The effects were variable across trials; one trial from a low prevalence setting carried out in 1995 found an increase in weight, but nine trials carried out since then found no effect, including five from moderate and high prevalence areas.,There is also reasonable evidence that regular treatment probably has no effect on average height (MD 0.02 cm higher, 95% CI 0.14 lower to 0.17 cm higher; 7057 participants, seven trials, moderate quality evidence); average haemoglobin (MD 0.02 g/dL lower; 95% CI 0.08 g/dL lower to 0.04 g/dL higher; 3595 participants, seven trials, low quality evidence); formal tests of cognition (32,486 participants, five trials, moderate quality evidence); exam performance (32,659 participants, two trials, moderate quality evidence); or mortality (1,005,135 participants, three trials, low quality evidence).,There is very limited evidence assessing an effect on school attendance and the findings are inconsistent, and at risk of bias (mean attendance 2% higher, 95% CI 4% lower to 8% higher; 20,243 participants, two trials, very low quality evidence).,In a sensitivity analysis that only included trials with adequate allocation concealment, there was no evidence of any effect for the main outcomes.,Treating children known to have worm infection may have some nutritional benefits for the individual.,However, in mass treatment of all children in endemic areas, there is now substantial evidence that this does not improve average nutritional status, haemoglobin, cognition, school performance, or survival.,In this Cochrane Review, Cochrane researchers examined the effects of deworming children in areas where intestinal worm infection is common.,After searching for relevant trials up to April 2015, we included 44 trials with a total of 67,672 participants, and an additional trial of one million children.,What is deworming and why might it be important,Soil‐transmitted worms, including roundworms, hookworms, and whipworms, are common in tropical and subtropical areas, and particularly affect children in low‐income areas where there is inadequate sanitation.,Heavy worm infection is associated with malnutrition, poor growth, and anaemia in children.,The World Health Organization currently recommends that school children in endemic areas are regularly treated with drugs which kill these worms.,The recommended drugs are effective at eliminating or greatly reducing worm infections, but the question remains whether doing so will reduce anaemia and improve growth, and consequently improve school attendance, school performance, and economic development, as has been claimed.,What the research says,In trials that treat only children known to be infected, deworming drugs may increase weight gain (low quality evidence), but we do not know if there is an effect on cognitive functioning or physical well‐being (very low quality evidence).,In trials treating all children living in an endemic area, deworming drugs have little or no effect on average weight gain (moderate quality evidence), haemoglobin (low quality evidence), or cognition (moderate quality evidence).,Regular deworming treatment every three to six months may also have little or no effect on average weight gain (low quality evidence).,The effects were variable across trials: one trial from 1995 in a low prevalence setting found an increase in weight, but nine trials carried out since then from moderate or high prevalence settings showed no effect.,There is good evidence that regular treatment probably has no effect on average height (moderate quality evidence), haemoglobin (low quality evidence), formal tests of cognition (moderate quality evidence), or exam performance (moderate quality evidence).,We do not know if there is an effect on school attendance (very low quality evidence).,Authors conclusions,Treating children known to have worm infection may improve weight gain but there is limited evidence of other benefits.,For routine deworming of school children in endemic areas, there is quite substantial evidence that deworming programmes do not show benefit in terms of average nutritional status, haemoglobin, cognition, school performance, or death.

Currently schistosomiasis transmission has been suppressed to low levels in many historically endemic areas of China by widespread use of praziquantel in human and bovine populations and application of niclosamide for snail control.,However, re-emergent transmission has signalled the need for sustainable interventions beyond these repeated chemical interventions.,To take advantage of ongoing investment in rural infrastructure, an index of schistosomiasis transmission potential is needed to identify villages where environmental modifications would be particularly effective.,Based on a retrospective analysis of data from 10 villages in Sichuan Province, an index linked to the basic reproductive number is shown to have promise in meeting this need.,However, a lack of methods for estimating the spatial components of the proposed metric and for estimating the import of cercariae and miracidia from neighbouring villages leads to significant uncertainty in its estimation.,These findings suggest a priority effort to develop methods for measuring the free-swimming forms of the parasite in surface waters.,This need is underscored by the high cost and limited sensitivity of current methods for diagnosing human infection and mounting evidence of the inadequacy of snail surveys to identify environments supporting low levels of transmission.

This prospective longitudinal birth cohort demonstrated that asymptomatic giardiasis in the first 6 months of life is a risk factor for poor linear growth.,Furthermore, asymptomatic giardiasis neither increases nor decreases odds of having an all cause acute diarrheal episode.,Background.,Growth stunting in children under 2 years of age in low-income countries is common.,Giardia is a ubiquitous pathogen in this age group but studies investigating Giardia's effect on both growth and diarrhea have produced conflicting results.,Methods.,We conducted a prospective longitudinal birth cohort study in Dhaka, Bangladesh, with monthly Giardia and continuous diarrheal surveillance.,Results. 629 children were enrolled within the first 72 hours of life, and 445 completed 2 years of the study. 12% of children were stunted at birth with 57% stunted by 2 years. 7% of children had a Giardia positive surveillance stool in the first 6 months of life, whereas 74% had a positive stool by 2 years.,The median time to first Giardia positive surveillance stool was 17 months.,Presence of Giardia in a monthly surveillance stool within the first 6 months of life decreased length-for-age Z score at 2 years by 0.4 (95% confidence interval, −.80 to −.001; P value .05) whereas total number of Giardia positive months over the 2-year period of observation did not.,Neither variable was associated with weight-for-age Z score at 2 years.,In our model to examine predictors of diarrhea only exclusive breastfeeding was significantly associated with decreased diarrhea (P value <.001).,Concomitant giardiasis was neither a risk factor nor protective.,Conclusions.,Early life Giardia was a risk factor for stunting at age 2 but not poor weight gain.,Presence of Giardia neither increased nor decreased odds of acute all cause diarrhea.

Cryptosporidium parvum is a zoonotic protozoan parasite found worldwide, that develops only in the gastrointestinal epithelium and causes profuse diarrhea.,Using a mouse model of C. parvum infection, we demonstrated by conditional depletion of CD11c+ cells that these cells are essential for the control of the infection both in neonates and adults.,Neonates are highly susceptible to C. parvum but the infection is self-limited, whereas adults are resistant unless immunocompromised.,We investigated the contribution of DC to the age-dependent susceptibility to infection.,We found that neonates presented a marked deficit in intestinal CD103+ DC during the first weeks of life, before weaning, due to weak production of chemokines by neonatal intestinal epithelial cells (IEC).,Increasing the number of intestinal CD103+ DC in neonates by administering FLT3-L significantly reduced susceptibility to the infection.,During infections in neonates, the clearance of the parasite was preceded by a rapid recruitment of CD103+ DC mediated by CXCR3-binding chemokines produced by IEC in response to IFNγ.,In addition to this key role in CD103+ DC recruitment, IFNγ is known to inhibit intracellular parasite development.,We demonstrated that during neonatal infection CD103+ DC produce IL-12 and IFNγ in the lamina propria and the draining lymph nodes.,Thus, CD103+DC are key players in the innate immune control of C. parvum infection in the intestinal epithelium.,The relative paucity of CD103+ DC in the neonatal intestine contributes to the high susceptibility to intestinal infection.

Changes in social, belief, and behavioural practices are essential for the success of any public health delivery programme.,In the planning stages of the Malaria Elimination Demonstration Project (MEDP), priority was given to communication with a goal to develop capacity of health workers and to improve the knowledge, attitude and practices (KAP) of the people of Mandla.,This paper describes the level of community knowledge on malaria, including its prevention, diagnosis, treatment-seeking behaviour, and the level of satisfaction with the services provided by the project.,A cross sectional survey was undertaken in 1233 villages of Mandla to study the KAP and self-assessed improvement in knowledge and satisfaction level of the community.,The goal of the study was to understand whether there is need for strengthening communication strategy of MEDP for better impact.,The survey was conducted amongst the head/eligible members of the 733 households located in the nine blocks of the district using clustered random sampling.,Though four-fifths of the respondents were able to correlate the transmission of malaria with mosquitoes, misconceptions existed among them.,The types of malaria were not known to everyone.,Only 39% were aware of the Indoor Residual Spray (IRS) and 41% understood the value of Long-Lasting Insecticidal Nets (LLIN).,Around 71% of subjects surveyed were aware of the proper diagnostic tests for malaria.,A total of 87% of the respondents knew about the MEDP staff working in their respective villages.,The study reported gaps in knowledge on malaria at community level.,The self-assessment of the community revealed that the communication strategy established by MEDP in Mandla district has been useful to them as they are becoming better informed about the prevention and treatment aspects of disease.,The lessons learned as revealed in the KAP survey will improve malaria elimination outcomes in a timely manner.

Malaria Elimination Demonstration Project (MEDP) was started as a Public-Private-Partnership between the Indian Council of Medical Research through National Institute of Research in Tribal Health, Govt. of Madhya Pradesh and Foundation of Disease Elimination and Control of India, which is a Corporate Social Responsibility (CSR) initiative of the Sun Pharmaceutical Industries Limited.,The project’s goal was to demonstrate that malaria can be eliminated from a high malaria endemic district along with prevention of re-establishment of malaria and to develop a model for malaria elimination using the lessons learned and knowledge acquired from the demonstration project.,The project employed tested protocols of robust surveillance, case management, vector control, and capacity building through continuous evaluation and training.,The model was developed using the learnings from the operational plan, surveillance and case management, monitoring and feedback, entomological investigations and vector control, IEC and capacity building, supply chain management, mobile application (SOCH), and independent reviews of MEDP.,The MEDP has been operational since April 2017 with field operations from August 2017, and has observed: (1) reduction in indigenous cases of malaria by about 91 %; (2) need for training and capacity building of field staff for diagnosis and treatment of malaria; (3) need for improvement insecticide spraying and for distribution and usage of bed-nets; (4) need for robust surveillance system that captures and documents information on febrile cases, RDT positive individuals, and treatments provided; (5) need for effective supervision of field staff based on advance tour plan; (6) accountability and controls from the highest level to field workers; and (7) need for context-specific IEC.,Malaria elimination is a high-priority public health goal of the Indian Government with a committed deadline of 2030.,In order to achieve this goal, built-in systems of accountability, ownership, effective management, operational, technical, and financial controls will be crucial components for malaria elimination in India.,This manuscript presents a model for malaria elimination with district as an operational unit, which may be considered for malaria elimination in India and other countries with similar geography, topography, climate, endemicity, health infrastructure, and socio-economic characteristics.

Cryptosporidium hominis and C. parvum are usually considered to be the major pathogens responsible for human cryptosporidiosis.,However, there have been few studies regarding the molecular epidemiology of Cryptosporidium in human infections in China.,Here we investigated Cryptosporidium infection in patients with diarrhea, in Danyang Hospital of Jiangsu Province, China, at the genotype level.,A total of 232 stool specimens were collected from outpatients with diarrhea in Danyang Hospital of Jiangsu Province, China, from February 2012 to January 2013.,Each specimen was stained from direct fecal smears and examined for Cryptosporidium using modified acid fast staining and microscopy.,Moreover, genomic DNA of each fecal sample was screened for the presence of Cryptosporidium with nested PCR, which was genotyped by analyzing the DNA sequences of small subunit rRNA (SSU rRNA).,The average infection rate of Cryptosporidium was 1.3% (3/232) by microscopy and subjected to PCR amplification of the SSU rRNA gene of Cryptosporidium, with 9.91% (23/232) being positive for Cryptosporidium with a significant peak in autumn.,Based on the SSU rRNA gene, two Cryptosporidium spp. were identified, including C. andersoni (n =21) and C. hominis (n =2).,Two types of C. andersoni, designated as A370+ and A370- , were found in the SSU rRNA gene in our present study, which was 100% homologous to C. andersoni infections derived from dairy calves and goats, respectively.,The clinical questionnaires showed no significant difference in age, gender and frequency of diarrhea, but duration of diarrhea was shorter for C. andersoni than that of C. hominis (mean, 2 vs. 4 days; p <0.01).,C. andersoni is the dominant species in Danyang City of Jiangsu Province.,The fact that SSU rRNA sequences of C. andersoni obtained from human stools exhibited 100% homologous to those derived from dairy calves and goats supported that C. andersoni infection might be attributable to animal origin.,The difference in the duration of diarrhea of C. andersoni and C. hominis indicated that different Cryptosporidium species might cause different clinical manifestations.

This study assessed the prevalence, species and subtypes of Cryptosporidium in goats from Guangdong Province, Hubei Province, Shandong Province, and Shanghai City of China.,Six hundred and four fecal samples were collected from twelve goat farms, and the overall infection rate was 11.4% (69/604).,Goats infected with Cryptosporidium were found in eleven farms across four provincial areas, and the infection rate ranged from 2.9% (1/35) to 25.0% (9/36).,Three Cryptosporidium species were identified.,Cryptosporidium xiaoi (45/69, 65.2%) was the dominant species, followed by C. parvum (14/69, 20.3%) and C. ubiquitum (10/69, 14.5%).,The infection rate of Cryptosporidium spp. was varied with host age and goat kids were more susceptible to be infected than adult goats.,Subtyping C. parvum and C. ubiquitum positive samples revealed C. parvum subtype IIdA19G1 and C. ubiquitum subtype XIIa were the most common subtypes.,Other C. parvum subtypes were detected as well, such as IIaA14G2R1, IIaA15G1R1, IIaA15G2R1 and IIaA17G2R1.,All of these subtypes have also been detected in humans, suggesting goats may be a potential source of zoonotic cryptosporidiosis.,This was the first report of C. parvum subtypes IIaA14G2R1, IIaA15G1R1 and IIaA17G2R1 infecting in goats and the first molecular identification of C. parvum and its subtypes in Chinese goats.

Maladaptive immune responses during cerebral malaria (CM) result in high mortality despite opportune anti-malarial chemotherapy.,Rapamycin, an FDA-approved immunomodulator, protects against experimental cerebral malaria (ECM) in mice through effects on the host.,However, the potential for reduced adaptive immunity with chronic use, combined with an incomplete understanding of mechanisms underlying protection, limit translational potential as an adjunctive therapy in CM.,The results presented herein demonstrate that a single dose of rapamycin, provided as late as day 4 or 5 post-infection, protected mice from ECM neuropathology and death through modulation of distinct host responses to infection.,Rapamycin prevented parasite cytoadherence in peripheral organs, including white adipose tissue, via reduction of CD36 expression.,Rapamycin also altered the splenic immune response by reducing the number of activated T cells with migratory phenotype, while increasing local cytotoxic T cell activation.,Finally, rapamycin reduced brain endothelial ICAM-1 expression concomitant with reduced brain pathology.,Together, these changes potentially contributed to increased parasite elimination while reducing CD8 T cell migration to the brain.,Rapamycin exerts pleotropic effects on host immunity, vascular activation and parasite sequestration that rescue mice from ECM, and thus support the potential clinical use of rapamycin as an adjunctive therapy in CM.

Malaria is a mosquito-borne infectious disease of humans.,It begins with a bite from an infected female Anopheles mosquito and leads to the development of the pre-erythrocytic and blood stages.,Blood-stage infection is the exclusive cause of clinical symptoms of malaria.,In contrast, the pre-erythrocytic stage is clinically asymptomatic and could be an excellent target for preventive therapies.,Although the robust host immune responses limit the development of the liver stage, malaria parasites have also evolved strategies to suppress host defenses at the pre-erythrocytic stage.,This paper reviews the immune evasion strategies of malaria parasites at the pre-erythrocytic stage, which could provide us with potential targets to design prophylactic strategies against malaria.

Malaria, the disease caused by Plasmodium spp. infection, remains a major global cause of morbidity and mortality, claiming the lives of over ∼4.5 × 105 individuals per year.,Paradoxically, however, up to 98% of infected individuals survive the infection, establishing disease tolerance to malaria.,We found that this host defense strategy, which does not target Plasmodium directly, relies on the capacity of renal proximal tubule epithelial cells to detoxify labile heme, a pathologic by-product of hemolysis that accumulates in plasma and urine during the blood stage of infection.,This defense strategy prevents the onset of acute kidney injury, a clinical hallmark of severe malaria.,Malaria, the disease caused by Plasmodium spp. infection, remains a major global cause of morbidity and mortality.,Host protection from malaria relies on immune-driven resistance mechanisms that kill Plasmodium.,However, these mechanisms are not sufficient per se to avoid the development of severe forms of disease.,This is accomplished instead via the establishment of disease tolerance to malaria, a defense strategy that does not target Plasmodium directly.,Here we demonstrate that the establishment of disease tolerance to malaria relies on a tissue damage-control mechanism that operates specifically in renal proximal tubule epithelial cells (RPTEC).,This protective response relies on the induction of heme oxygenase-1 (HMOX1; HO-1) and ferritin H chain (FTH) via a mechanism that involves the transcription-factor nuclear-factor E2-related factor-2 (NRF2).,As it accumulates in plasma and urine during the blood stage of Plasmodium infection, labile heme is detoxified in RPTEC by HO-1 and FTH, preventing the development of acute kidney injury, a clinical hallmark of severe malaria.

Malaria reduces host fitness and survival by pathogen-mediated damage and inflammation.,Disease tolerance mechanisms counter these negative effects without decreasing pathogen load.,Here, we demonstrate that in four different mouse models of malaria, adrenal hormones confer disease tolerance and protect against early death, independently of parasitemia.,Surprisingly, adrenalectomy differentially affects malaria-induced inflammation by increasing circulating cytokines and inflammation in the brain but not in the liver or lung.,Furthermore, without affecting the transcription of hepatic gluconeogenic enzymes, adrenalectomy causes exhaustion of hepatic glycogen and insulin-independent lethal hypoglycemia upon infection.,This hypoglycemia is not prevented by glucose administration or TNF-α neutralization.,In contrast, treatment with a synthetic glucocorticoid (dexamethasone) prevents the hypoglycemia, lowers cerebral cytokine expression and increases survival rates.,Overall, we conclude that in malaria, adrenal hormones do not protect against lung and liver inflammation.,Instead, they prevent excessive systemic and brain inflammation and severe hypoglycemia, thereby contributing to tolerance.,Disease tolerance mechanisms counter the negative effects of infection without decreasing the pathogen load.,Here, the authors show that in mouse models of malaria, such disease tolerance can be conferred by adrenal hormones, by preventing excessive inflammation and hypoglycemia.

Cutaneous leishmaniasis (CL) is treated with parenteral drugs for decades with decreasing rate cures.,Miltefosine is an oral medication with anti-leishmania activity and may increase the cure rates and improve compliance.,This study is a randomized, open-label, controlled clinical trial aimed to evaluate the efficacy and safety of miltefosine versus pentavalent antimony (Sbv) in the treatment of patients with CL caused by Leishmania braziliensis in Bahia, Brazil.,A total of 90 patients were enrolled in the trial; 60 were assigned to receive miltefosine and 30 to receive Sbv.,Six months after treatment, in the intention-to-treat analyses, the definitive cure rate was 53.3% in the Sbv group and 75% in the miltefosine group (difference of 21.7%, 95% CI 0.08% to 42.7%, p = 0.04).,Miltefosine was more effective than Sbv in the age group of 13-65 years-old compared to 2-12 years-old group (78.9% versus 45% p = 0.02; 68.2% versus 70% p = 1.0, respectively).,The incidence of adverse events was similar in the Sbv and miltefosine groups (76.7% vs.,78.3%).,Vomiting (41.7%), nausea (40%), and abdominal pain (23.3%) were significantly more frequent in the miltefosine group while arthralgias (20.7%), mialgias (20.7%) and fever (23.3%) were significantly more frequent in the Sbv group.,This study demonstrates that miltefosine therapy is more effective than standard Sbv and safe for the treatment of CL caused by Leishmania braziliensis in Bahia, Brazil.,Clinicaltrials.gov Identifier NCT00600548

Cutaneous Leishmania major has affected many travelers including military personnel in Iraq and Afghanistan.,Optimal treatment for this localized infection has not been defined, but interestingly the parasite is thermosensitive.,Participants with parasitologically confirmed L. major infection were randomized to receive intravenous sodium stibogluconate (SSG) 20mg/kg/day for ten doses or localized ThermoMed (TM) device heat treatment (applied at 50°C for 30 seconds) in one session.,Those with facial lesions, infection with other species of Leishmania, or more than 20 lesions were excluded.,Primary outcome was complete re-epithelialization or visual healing at two months without relapse over 12 months.,Fifty-four/56 enrolled participants received intervention, 27 SSG and 27 TM.,In an intent to treat analysis the per subject efficacy at two months with 12 months follow-up was 54% SSG and 48% TM (p = 0.78), and the per lesion efficacy was 59% SSG and 73% TM (p = 0.053).,Reversible abdominal pain/pancreatitis, arthralgias, myalgias, headache, fatigue, mild cytopenias, and elevated transaminases were more commonly present in the SSG treated participants, whereas blistering, oozing, and erythema were more common in the TM arm.,Skin lesions due to L. major treated with heat delivered by the ThermoMed device healed at a similar rate and with less associated systemic toxicity than lesions treated with intravenous SSG.,ClinicalTrials.gov NCT 00884377

Rapid diagnostic test (RDT) is an important tool for parasite-based malaria diagnosis.,High specificity of RDTs to distinguish an active Plasmodium falciparum infection from residual antigens from a previous infection is crucial in endemic areas where residents are repeatedly exposed to malaria.,The efficiency of two RDTs based on histidine-rich protein 2 (HRP2) and lactate dehydrogenase (LDH) antigens were studied and compared with two microscopy techniques (Giemsa and acridine orange-stained blood smears) and real-time polymerase chain reaction (PCR) for assessment of initial clearance and detection of recurrent P. falciparum infections after artemisinin-based combination therapy (ACT) in a moderately high endemic area of rural Tanzania.,In this exploratory study 53 children < five years with uncomplicated P. falciparum malaria infection were followed up on nine occasions, i.e., day 1, 2, 3, 7, 14, 21, 28, 35 and 42, after initiation of artemether-lumefantrine treatment.,At each visit capillary blood samples was collected for the HRP2 and LDH-based RDTs, Giemsa and acridine orange-stained blood smears for microscopy and real-time PCR.,Assessment of clearance times and detection of recurrent P. falciparum infections were done for all diagnostic methods.,The median clearance times were 28 (range seven to >42) and seven (two to 14) days for HRP2 and LDH-based RDTs, two (one to seven) and two (one to 14) days for Giemsa and acridine orange-stained blood smear and two (one to 28) days for real-time PCR.,RDT specificity against Giemsa-stained blood smear microscopy was 21% for HRP2 on day 14, reaching 87% on day 42, and ≥96% from day 14 to 42 for LDH.,There was no significant correlation between parasite density at enrolment and duration of HRP2 positivity (r = 0.13, p = 0.34).,Recurrent malaria infections occurred in ten (19%) children.,The HRP2 and LDH-based RDTs did not detect eight and two of the recurrent infections, respectively.,The LDH-based RDT was superior to HRP2-based for monitoring of treatment outcome and detection of recurrent infections after ACT in this moderately high transmission setting.,The results may have implications for the choice of RDT devices in similar transmission settings for improved malaria case management.,Clinicaltrials.gov, NCT01843764

New diagnostic tools for malaria are required owing to the changing epidemiology of malaria, particularly among pregnant women in sub-Saharan Africa.,Real-time PCR assays targeting Plasmodium falciparum lactate dehydrogenase (pfldh) gene may facilitate the identification of a high proportion of pregnant women with a P. falciparum parasitaemia below the threshold of microscopy.,These molecular methods will enable further studies on the effects of these submicroscopic infections on maternal health and birth outcomes.,The pfldh real-time PCR assay and conventional microscopy were compared for the detection of P. falciparum from dried blood spots and blood smears collected from the peripheral blood of 475 Malawian women at delivery.,A cycle threshold (Ct) of the real-time PCR was determined optimizing the sensitivity and specificity of the pfldh PCR assay compared to microscopy.,A real-time PCR species-specific assay was applied to identify the contribution to malaria infections of three Plasmodium species (P. falciparum P. ovale and P. malariae) in 44 discordant smear and pfldh PCR assay results.,Of the 475 women, P. falciparum was detected in 11 (2.3%) by microscopy and in 51 (10.7%) by real-time PCR; compared to microscopy, the sensitivity of real-time PCR was 90.9% and the specificity 91.2%.,If a Ct value of 38 was used as a cut-off, specificity improved to 94.6% with no change in sensitivity.,The real-time PCR species-specific assay detected P. falciparum alone in all but four samples: two samples were mixed infections with P. falciparum and P. malariae, one was a pure P. malariae infection and one was a pfldh PCR assay-positive/species-specific assay-negative sample.,Of three P. malariae infections detected by microscopy, only one was confirmed by the species-specific assay.,Although microscopy remains the most appropriate method for clinical malaria diagnosis in field settings, molecular diagnostics such as real-time PCR offer a more reliable means to detect malaria parasites, particularly at low levels.,Determination of the possible contribution of these submicroscopic infections to poor birth outcomes and maternal health is critical.,For future studies to investigate these effects, this pfldh real-time PCR assay offers a reliable detection method.

With increasing levels of enrolment, primary schools present a pragmatic opportunity to improve the access of school children to timely diagnosis and treatment of malaria, increasingly recognised as a major health problem within this age group.,The expanded use of malaria rapid diagnostic tests (RDTs) and artemisinin combination therapy (ACT) by community health workers (CHWs) has raised the prospect of whether teachers can provide similar services for school children.,We describe and evaluate the training of primary school teachers to use a first aid kit containing malaria RDTs and ACT for the diagnosis and treament of uncomplicated malaria in school children in southern Malawi.,We outline the development of the intervention as: (1) conception and design, (2) pilot training, (3) final training, and (4) 7-month follow up.,The training materials were piloted at a four-day workshop in July 2013 following their design at national stakeholders meetings.,The evaluation of the pilot training and materials were assessed in relation to increased knowledge and skill sets using checklist evaluations and questionnaires, the results of which informed the design of a final seven-day training programme held in December 2013.,A follow up of trained teachers was carried out in July 2014 following 7 months of routine implementation.,A total of 15 teachers were evaluated at four stages: pilot training, two weeks following pilot, final training and seven months following final training.,A total of 15 and 92 teachers were trained at the pilot and final training respectively.,An average of 93 % of the total steps required to use RDTs were completed correctly at the final training, declining to 87 % after 7 months.,All teachers were observed correctly undertaking safe blood collection and handling, accurate RDT interpretation, and correct dispensing of ACT.,The most commonly observed errors were a failure to wait 20 minutes before reading the test result, and adding an incorrect volume of buffer to the test cassette.,Following training, teachers are able to competently use RDTs and ACTs test and treat children at school for uncomplicated malaria safely and accurately.,Teachers demonstrate a comparable level of RDT use relative to non-health professional users of RDTs, and sustain this competency over a period of seven months during routine implementation.

Malaria treatment policy has changed from presumptive treatment to targeted “test and treat” (T&T) with malaria rapid diagnostic tests (RDTs) and artemisinin combination therapy (ACT).,This transition involves changing behavior among health providers, meaning delays between introduction and full implementation are recorded in almost every instance.,We investigated factors affecting successful transition, and suggest approaches for accelerating uptake of T&T.,Records from 2000 to 2011 from health clinics in Senegal where malaria is mesoendemic were examined (96,166 cases).,The study period encompassed the implementation of national T&T policy in 2006.,Analysis showed that adherence to test results is the first indicator of T&T adoption and is dependent on accumulation of experience with positive RDTs (odds ratio [OR]: 0.55 [P ≤ 0.001], 95% confidence interval [CI]: 0.53-0.58).,Reliance on tests for malaria diagnosis (rather than presumptive diagnosis) followed after test adherence is achieved, and was also associated with increased experience with positive RDTs (OR: 0.60 [P ≤ 0.001], 95% CI: 0.58-0.62).,Logistic models suggest that full adoption of T&T clinical practices can occur within 2 years, that monitoring these behavioral responses rather than RDT or ACT consumption will improve evaluation of T&T uptake, and that accelerating T&T uptake by focusing training on adherence to test results will reduce overdiagnosis and associated health and economic costs in mesoendemic regions.

The epidemiology of soil-transmitted helminth (STH) and Plasmodium co-infections need better understanding.,The findings of the individual studies are inconclusive.,A systematic review was conducted to synthesize evidence on the association of STH infection with the prevalence and density of Plasmodium falciparum infection, and its effect on anaemia among children in sub-Saharan Africa (SSA).,Relevant studies published before March 6, 2015 were identified by searching Medline (via Pubmed), Embase, Cochrane Library and CINAHL without any language restriction.,Studies on P. falciparum and STH co-infection among children in SSA except for case studies were included in this study.,Studies were screened for eligibility and data extracted independently by two authors.,The primary outcome assessed was the prevalence of P. falciparum infection and the secondary outcomes included P. falciparum density and prevalence of anaemia.,Heterogeneity was assessed using Cochrane Q and Moran’s I2 and publication bias was evaluated using Egger test.,A random-effects model was used to estimate the summary odds ratio (OR) and the corresponding 95 % confidence intervals (CI).,Out of 2985 articles screened, 11 articles were included in the systematic review; of these seven were considered in the meta-analysis.,Of the 11 studies with 7458 study participants, seven were cross-sectional, one prospective cohort and three were randomized controlled trials.,Four studies examined the outcome for hookworms, one for Ascaris lumbricoides and six for pooled (at least one) STH species.,Eight studies measured prevalence/incidence of uncomplicated P. falciparum infection, two calculated prevalence of asymptomatic P. falciparum infection, three evaluated P. falciparum density and four considered prevalence of P. falciparum infection related anaemia/mean haemoglobin reduction.,The odds of asymptomatic/uncomplicated P. falciparum infection were higher among children infected with STH than those uninfected with intestinal helminths (summary Odds Ratio [OR]: 1.4; 95 % Confidence Interval [CI]: 1.05-1.87; I2 = 36.8 %).,Plasmodium falciparum density tended to be higher among children infected with STH than those uninfected with intestinal helminths.,However, STH infection was associated with lower odds of P. falciparum infection related anaemia (summary OR: 0.5; 95 % CI: 0.21-0.78; I2 = 43.3 %).,The findings suggest that STH infection may increase susceptibility to asymptomatic/uncomplicated P. falciparum infection but may protect malaria-related anaemia in children.,Future studies should investigate the effect of STH infection upon the incidence of severe P. falciparum infection among children in SSA.,The online version of this article (doi:10.1186/s13071-016-1594-2) contains supplementary material, which is available to authorized users.

Anaemia reduces cognitive potential in school children, retards their growth and predisposes them to other diseases.,As there is a paucity of data on the current burden of P. falciparum, S. mansoni and soil transmitted helminths (STH) infections and their correlation with schoolchildren’s anemia in the Democratic Republic of Congo (DRC), we collect these data.,This study reports baseline data collected from a randomized controlled trial investigating the impact of IPT with SP and SP-PQ on anemia and malaria morbidity in Congolese schoolchildren (Trial registration: NCT01722539; PACTR201211000449323).,S. mansoni and STH infections were assessed using kato-katz technique.,Malaria infection and hemoglobin concentration were assessed using Blood smear and Hemocontrol device, respectively.,A total of 616 primary schoolchildren from 4 to 13 years old were enrolled in the study.,The prevalence of Plasmodium spp. infection was 18.5% (95%CI:15.6-21.9).,Amongst those infected, 24 (21%), 40 (35.1%), 40 (35.1%), 10 (8.8%), had light, moderate, heavy, very high malaria parasite density, respectively.,Above 9 years of age (p = 0.02), male and history of fever (p = 0.04) were both associated with malaria infection.,The overall prevalence of S. mansoni infection was 6.4% (95%CI:4.4-9.1).,Girls were associated with S. mansoni infection (p = 0.04).,T. trichiura was the most prevalent STH infection (26.3%), followed by A. lumbricoides (20.1%).,Co-infection with malaria-S. mansoni and malaria-STH was, respectively, 1.5% (CI95%:0.7-3.3) and 6.4% (CI95% 4.4-9.1).,The prevalence of anemia was found to be 41.6% (95%CI:37.7-45.6) and anemia was strongly related with Plasmodium ssp infection (aOR:4.1; CI95%:2.6-6.5;p<0.001) and S. mansoni infection (aOR:3.3;CI95%:1.4-7.8;p<0.01).,Malaria and S. mansoni infection were strongly associated with high prevalence of anemia in schoolchildren.,Therefore, specific school-based interventions, such as intermittent preventive treatment or prophylaxis, LLITN distribution, anthelminthic mass treatment and micronutrient supplementation are needed to improve school children’s health.

A mixed methods study was conducted to look at the magnitude of residual malaria transmission (RMT) and factors contributing to low (< 1% prevalence), but sustained transmission in rural communities on the Thai-Myanmar border.,A cross-sectional behaviour and net survey, observational surveys and entomological collections in both villages and forested farm huts frequented by community members for subsistence farming practices were conducted.,Community members frequently stayed overnight at subsistence farm huts or in the forest.,Entomological collections showed higher biting rates of primary vectors in forested farm hut sites and in a more forested village setting compared to a village with clustered housing and better infrastructure.,Despite high levels of outdoor biting, biting exposure occurred predominantly indoors, particularly for non-users of long-lasting insecticidal nets (LLINs).,Risk of biting exposure was exacerbated by sub-optimal coverage of LLINs, particularly in subsistence farm huts and in the forest.,Furthermore, early waking hours when people had left the safety of their nets coincided with peaks in biting in later morning hours.,Entomological and epidemiological findings suggest drivers and modulators of sustained infection prevalence in the area to be: higher mosquito abundance in forested areas where LLINs were used less frequently or could not be used; late sleeping and waking times coinciding with peak biting hours; feeding preferences of Anopheles taking them away from contact with LLIN and indoor residual spraying (IRS), e.g. exophagy and zoophagy; non-use of LLIN and use of damaged/torn LLIN; high population movement across the border and into forested areas thereby increasing risk of exposure, decreasing use of protection and limiting access to healthcare; and, Plasmodium vivax predominance resulting in relapse(s) of previous infection.,The findings highlight gaps in current intervention coverage beyond the village setting.,The online version of this article (10.1186/s12936-019-2852-5) contains supplementary material, which is available to authorized users.

It has been speculated that widespread and sustained use of insecticide treated bed nets (ITNs) for over 10 years in Asembo, western Kenya, may have selected for changes in the location (indoor versus outdoor) and time (from late night to earlier in the evening) of biting of the predominant species of human malaria vectors (Anopheles funestus, Anopheles gambiae sensu stricto, and Anopheles arabiensis).,Mosquitoes were collected by human landing catches over a six week period in June and July, 2011, indoors and outdoors from 17 h to 07 h, in 75 villages in Asembo, western Kenya.,Collections were separated by hour of the night, and mosquitoes were identified to species and tested for sporozoite infection with Plasmodium falciparum.,A subset was dissected to determine parity.,Human behavior (time going to bed and rising, time spent indoors and outdoors) was quantified by cross-sectional survey.,Data from past studies of a similar design and in nearby settings, but conducted before the ITN scale up commenced in the early 2000s, were compared with those from the present study.,Of 1,960 Anopheles mosquitoes collected in 2011, 1,267 (64.6%) were morphologically identified as An. funestus, 663 (33.8%) as An. gambiae sensu lato (An. gambiae s.s. and An. arabiensis combined), and 30 (1.5%) as other anophelines.,Of the 663 An. gambiae s.l. collected, 385 were successfully tested by PCR among which 235 (61.0%) were identified as An. gambiae s.s. while 150 (39.0%) were identified as An. arabiensis.,Compared with data collected before the scale-up of ITNs, daily entomological inoculation rates (EIRs) were consistently lower for An. gambiae s.l. (indoor EIR = 0.432 in 1985-1988, 0.458 in 1989-1990, 0.023 in 2011), and An. arabiensis specifically (indoor EIR = 0.532 in 1989-1990, 0.039 in 2009, 0.006 in 2011) but not An. funestus (indoor EIR = 0.029 in 1985-1988, 0.147 in 1989-1990, 0.010 in 2009 and 0.103 in 2011).,Sporozoite rates were lowest in 2009 but rose again in 2011.,Compared with data collected before the scale-up of ITNs, An. arabiensis and An. funestus were more likely to bite outdoors and/or early in the evening (p < 0.001 for all comparisons).,However, when estimates of human exposure that would occur indoors (πi) or while asleep (πs) in the absence of an ITN were generated based on human behavioral patterns, the changes were modest with >90% of exposure of non-ITN users to mosquito bites occurring while people were indoors in all years.,The proportion of bites occurring among non-ITN users while they were asleep was ≥90% for all species except for An. arabiensis.,For this species, 97% of bites occurred while people were asleep in 1989-1990 while in 2009 and 2011, 80% and 84% of bites occurred while people were asleep for those not using ITNs.,Assuming ITNs prevent a theoretical maximum of 93.7% of bites, it was estimated that 64-77% of bites would have occurred among persons using nets while they were asleep in 1989-1990, while 20-52% of bites would have occurred among persons using nets while they were asleep in 2009 and 2011.,This study found no evidence to support the contention that populations of Anopheles vectors of malaria in Asembo, western Kenya, are exhibiting departures from the well-known pattern of late night, indoor biting characteristic of these typically highly anthropophilic species.,While outdoor, early evening transmission likely does occur in western Kenya, the majority of transmission still occurs indoors, late at night.,Therefore, malaria control interventions such as ITNs that aim to reduce indoor biting by mosquitoes should continue to be prioritized.

Malaria still causes high morbidity and mortality around the world, mainly in sub-Saharan Africa.,Community case management of malaria (CCMm) by community health workers (CHWs) is one of the strategies to combat the disease by increasing access to malaria treatment.,Currently, the World Health Organization recommends to treat only confirmed malaria cases, rather than to give presumptive treatment.,This systematic review aims to provide a comprehensive overview of the success or failure of critical steps in CCMm with rapid diagnostic tests (RDTs).,The databases of Medline, Embase, the Cochrane Library, the library of the ‘Malaria in Pregnancy’ consortium, and Web of Science were used to find studies on CCMm with RDTs in SSA.,Studies were selected according to inclusion and exclusion criteria, subsequently risk of bias was assessed and data extracted.,27 articles were included.,CHWs were able to correctly perform RDTs, although specificity levels were variable.,CHWs showed high adherence to test results, but in some studies a substantial group of RDT negatives received treatment.,High risk of bias was found for morbidity and mortality studies, therefore, effects on morbidity and mortality could not be estimated.,Uptake and acceptance by the community was high, however negative-tested patients did not always follow up referral advice.,Drug or RDT stock-outs and limited information on CHW motivation are bottlenecks for sustainable implementation.,RDT-based CCMm was found to be cost effective for the correct treatment of malaria in areas with low to medium malaria prevalence, but study designs were not optimal.,Trained CHWs can deliver high quality care for malaria using RDTs.,However, lower RDT specificity could lead to missed diagnoses of non-malarial causes of fever.,Other threats for CCMm are non-adherence to negative test results and low referral completion.,Integrated CCM may solve some of these issues.,Unfortunately, morbidity and mortality are not adequately investigated.,More information is needed about influencing sociocultural aspects, CHW motivation and stock supply.,CCMm is generally well executed by CHWs, but there are several barriers for its success.,Integrated CCM may overcome some of these barriers.

Many malarious countries plan to introduce artemisinin combination therapy (ACT) at community level using community health workers (CHWs) for treatment of uncomplicated malaria.,Use of ACT with reliance on presumptive diagnosis may lead to excessive use, increased costs and rise of drug resistance.,Use of rapid diagnostic tests (RDTs) could address these challenges but only if the communities will accept their use by CHWs.,This study assessed community acceptability of the use of RDTs by Ugandan CHWs, locally referred to as community medicine distributors (CMDs).,The study was conducted in Iganga district using 10 focus group discussions (FGDs) with CMDs and caregivers of children under five years, and 10 key informant interviews (KIIs) with health workers and community leaders.,Pre-designed FGD and KII guides were used to collect data.,Manifest content analysis was used to explore issues of trust and confidence in CMDs, stigma associated with drawing blood from children, community willingness for CMDs to use RDTs, and challenges anticipated to be faced by the CMDs.,CMDs are trusted by their communities because of their commitment to voluntary service, access, and the perceived effectiveness of anti-malarial drugs they provide.,Some community members expressed fear that the blood collected could be used for HIV testing, the procedure could infect children with HIV, and the blood samples could be used for witchcraft.,Education level of CMDs is important in their acceptability by the community, who welcome the use of RDTs given that the CMDs are trained and supported.,Anticipated challenges for CMDs included transport for patient follow-up and picking supplies, adults demanding to be tested, and caregivers insisting their children be treated instead of being referred.,Use of RDTs by CMDs is likely to be acceptable by community members given that CMDs are properly trained, and receive regular technical supervision and logistical support.,A well-designed behaviour change communication strategy is needed to address the anticipated programmatic challenges as well as community fears and stigma about drawing blood.,Level of formal education may have to be a criterion for CMD selection into programmes deploying RDTs.

A chemically diverse range of novel tetraoxanes was synthesized and evaluated in vitro against intramacrophage amastigote forms of Leishmania donovani.,All 15 tested tetraoxanes displayed activity, with IC50 values ranging from 2 to 45 µm.,The most active tetraoxane, compound LC140, exhibited an IC50 value of 2.52 ± 0.65 µm on L. donovani intramacrophage amastigotes, with a selectivity index of 13.5.,This compound reduced the liver parasite burden of L. donovani-infected mice by 37% after an intraperitoneal treatment at 10 mg/kg/day for five consecutive days, whereas miltefosine, an antileishmanial drug in use, reduced it by 66%.,These results provide a relevant basis for the development of further tetraoxanes as effective, safe, and cheap drugs against leishmaniasis.

Miltefosine (MIL) is an oral antileishmanial drug used for treatment of visceral leishmaniasis (VL) in the Indian subcontinent.,Recent reports indicate a significant decline in its efficacy with a high rate of relapse in VL as well as post kala-azar dermal leishmaniasis (PKDL).,We investigated the parasitic factors apparently involved in miltefosine unresponsiveness in clinical isolates of Leishmania donovani.,L. donovani isolated from patients of VL and PKDL at pretreatment stage (LdPreTx, n = 9), patients that relapsed after MIL treatment (LdRelapse, n = 7) and parasites made experimentally resistant to MIL (LdM30) were included in this study.,MIL uptake was estimated using liquid chromatography coupled mass spectrometry.,Reactive oxygen species and intracellular thiol content were measured fluorometrically.,Q-PCR was used to assess the differential expression of genes associated with MIL resistance.,LdRelapse parasites exhibited higher IC50 both at promastigote level (7.92 ± 1.30 μM) and at intracellular amastigote level (11.35 ± 6.48 μM) when compared with LdPreTx parasites (3.27 ± 1.52 μM) and (3.85 ± 3.11 μM), respectively.,The percent infectivity (72 hrs post infection) of LdRelapse parasites was significantly higher (80.71 ± 5.67%, P<0.001) in comparison to LdPreTx (60.44 ± 2.80%).,MIL accumulation was significantly lower in LdRelapse parasites (1.7 fold, P<0.001) and in LdM30 parasites (2.4 fold, P<0.001) when compared with LdPreTx parasites.,MIL induced ROS levels were significantly lower (p<0.05) in macrophages infected with LdRelapse while intracellular thiol content were significantly higher in LdRelapse compared to LdPreTx, indicating a better tolerance for oxidative stress in LdRelapse isolates.,Genes associated with oxidative stress, metabolic processes and transporters showed modulated expression in LdRelapse and LdM30 parasites in comparison with LdPreTx parasites.,The present study highlights the parasitic factors and pathways responsible for miltefosine unresponsiveness in VL and PKDL.

Tissue invasive helminth infections and tuberculosis (TB) are co-endemic in many parts of the world and can trigger immune responses that might antagonize each other.,We have previously shown that helminth infections modulate the Th1 and Th17 responses to mycobacterial-antigens in latent TB.,To determine whether helminth infections modulate antigen-specific and non-specific immune responses in active pulmonary TB, we examined CD4+ and CD8+ T cell responses as well as the systemic (plasma) cytokine levels in individuals with pulmonary TB with or without two distinct helminth infections-Wuchereria bancrofti and Strongyloides stercoralis infection.,By analyzing the frequencies of Th1 and Th17 CD4+ and CD8+ T cells and their component subsets (including multifunctional cells), we report a significant diminution in the mycobacterial-specific frequencies of mono- and multi-functional CD4+ Th1 and (to a lesser extent) Th17 cells when concomitant filarial or Strongyloides infection occurs.,The impairment in CD4+ and CD8+ T cell cytokine responses was antigen-specific as polyclonal activated T cell frequencies were equivalent irrespective of helminth infection status.,This diminution in T cell responses was also reflected in diminished circulating levels of Th1 (IFN-γ, TNF-α and IL-2)- and Th17 (IL-17A and IL-17F)-associated cytokines.,Finally, we demonstrate that for the filarial co-infections at least, this diminished frequency of multifunctional CD4+ T cell responses was partially dependent on IL-10 as IL-10 blockade significantly increased the frequencies of CD4+ Th1 cells.,Thus, co-existent helminth infection is associated with an IL-10 mediated (for filarial infection) profound inhibition of antigen-specific CD4+ T cell responses as well as protective systemic cytokine responses in active pulmonary TB.

Preexisting helminth infection impairs immunity against subsequent M. tuberculosis infection, in part by inducing alternatively activated macrophages.,Tuberculosis and helminthic infections coexist in many parts of the world, yet the impact of helminth-elicited Th2 responses on the ability of the host to control Mycobacterium tuberculosis (Mtb) infection has not been fully explored.,We show that mice infected with the intestinal helminth Nippostrongylus brasiliensis (Nb) exhibit a transitory impairment of resistance to airborne Mtb infection.,Furthermore, a second dose of Nb infection substantially increases the bacterial burden in the lungs of co-infected mice.,Interestingly, the Th2 response in the co-infected animals did not impair the onset and development of the protective Mtb-specific Th1 cellular immune responses.,However, the helminth-induced Th2 environment resulted in the accumulation of alternatively activated macrophages (AAMs) in the lung.,Co-infected mice lacking interleukin (IL) 4Rα exhibited improved ability to control Mtb infection, which was accompanied by significantly reduced accumulation of AAMs.,Moreover, IL-4Rα−/− mice adoptively transferred with wild-type macrophages had a significantly higher Mtb load in their lungs compared with those that received IL-4Rα−/− macrophages, suggesting a direct contribution for the IL-4R pathway to the heightened susceptibility of co-infected animals.,The Th2 response can thus enhance the intracellular persistence of Mtb, in part by mediating the alternative activation of macrophages via the IL-4Rα signaling pathway.

Resistance to first-line treatments for Plasmodium falciparum malaria and the insecticides used for Anopheles vector control are threatening malaria elimination efforts.,Suboptimal responses to drugs and insecticides are both spreading geographically and emerging independently and are being seen at increasing intensities.,Whilst resistance is unavoidable, its effects can be mitigated through resistance management practices, such as exposing the parasite or vector to more than one selective agent.,Resistance contributed to the failure of the 20th century Global Malaria Eradication Programme, and yet the global response to this issue continues to be slow and poorly coordinated-too often, too little, too late.,The Malaria Eradication Research Agenda (malERA) Refresh process convened a panel on resistance of both insecticides and antimalarial drugs.,This paper outlines developments in the field over the past 5 years, highlights gaps in knowledge, and proposes a research agenda focused on managing resistance.,A deeper understanding of the complex biological processes involved and how resistance is selected is needed, together with evidence of its public health impact.,Resistance management will require improved use of entomological and parasitological data in decision making, and optimisation of the useful life of new and existing products through careful implementation, combination, and evaluation.,A proactive, collaborative approach is needed from basic science and the development of new tools to programme and policy interventions that will ensure that the armamentarium of drugs and insecticides is sufficient to deal with the challenges of malaria control and its elimination.,Janet Hemingway and colleagues examine progress in research on insecticide and drug resistance in malaria elimination and eradication and propose a research agenda.

Public health measures are poised for transition from malaria control to malaria elimination on the island of Hispaniola.,Assessment of the reservoir of asymptomatic infections from which acute malaria cases may derive is critical to plan and evaluate elimination efforts.,Current field technology is ill suited for detecting sub-microscopic infections, thus highly sensitive survey methods capable of detecting virtually all infections are needed.,In this study the prevalence of infection with Plasmodium falciparum was determined in patients seeking medical care primarily for non-febrile conditions in six departments in Haiti using a newly designed qRT-PCR-based assay.,Three different methods of parasite detection were compared to assess their utility in approximating the prevalence of P. falciparum infections in the population: malaria rapid diagnostic test (RDT) designed to detect histidine-rich protein 2 (HRP2), thick smear microscopy, and a quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay based upon the small sub-unit ribosomal RNA.,The limit of detection of the qRT-PCR assay utilized was 0.0003 parasite/µL of blood.,Venous blood was obtained from a total of 563 subjects from six departments in Haiti, all of whom were seeking medical attention without complaints consistent with malaria.,Each subject was questioned for knowledge and behaviour using demographic and epidemiological survey to identify risk factors for disease transmission.,Among the 563 samples tested, ten and 16 were found positive for malaria by RDT and microscopy, respectively.,Using the qRT-PCR test to assess the infection status of these subjects, an additional 92 were identified for a total of 108.,Based upon the qRT-PCR assay results, a wide variation in prevalence of infection in asymptomatic subjects was seen between geographic locations ranging from 4-41 %.,The prevalence of infection was highest in the Grand Anse, Nord and Sud-Est Departments, and demographic data from questionnaires provide evidence for focal disease transmission.,The qRT-PCR assay is sufficiently sensitive to identify an unexpectedly large number of asymptomatic, submicroscopic infections.,Identifying and clearing these infections presents a significant challenge to both control and elimination efforts, but the qRT-PCR assay offers a reliable method to identify them.

The effectiveness of long-lasting, insecticidal nets (LLINs) in preventing malaria is threatened by the changing biting behaviour of mosquitoes, from nocturnal and endophagic to crepuscular and exophagic, and by their increasing resistance to insecticides.,Using epidemiological stochastic simulation models, we studied the impact of a mass LLIN distribution on Plasmodium falciparum malaria.,Specifically, we looked at impact in terms of episodes prevented during the effective life of the batch and in terms of net health benefits (NHB) expressed in disability adjusted life years (DALYs) averted, depending on biting behaviour, resistance (as measured in experimental hut studies), and on pre-intervention transmission levels.,Results were very sensitive to assumptions about the probabilistic nature of host searching behaviour.,With a shift towards crepuscular biting, under the assumption that individual mosquitoes repeat their behaviour each gonotrophic cycle, LLIN effectiveness was far less than when individual mosquitoes were assumed to vary their behaviour between gonotrophic cycles.,LLIN effectiveness was equally sensitive to variations in host-searching behaviour (if repeated) and to variations in resistance.,LLIN effectiveness was most sensitive to pre-intervention transmission level, with LLINs being least effective at both very low and very high transmission levels, and most effective at around four infectious bites per adult per year.,A single LLIN distribution round remained cost effective, except in transmission settings with a pre-intervention inoculation rate of over 128 bites per year and with resistant mosquitoes that displayed a high proportion (over 40%) of determined crepuscular host searching, where some model variants showed negative NHB.,Shifts towards crepuscular host searching behaviour can be as important in reducing LLIN effectiveness and cost effectiveness as resistance to pyrethroids.,As resistance to insecticides is likely to slow down the development of behavioural resistance and vice versa, the two types of resistance are unlikely to occur within the same mosquito population.,LLINs are likely cost effective interventions against malaria, even in areas with strong resistance to pyrethroids or where a large proportion of host-mosquito contact occurs during times when LLIN users are not under their nets.

A research priority for Plasmodium vivax malaria is to improve our understanding of the spatial distribution of risk and its relationship with the burden of P. vivax disease in human populations.,The aim of the research outlined in this article is to provide a contemporary evidence-based map of the global spatial extent of P. vivax malaria, together with estimates of the human population at risk (PAR) of any level of transmission in 2009.,The most recent P. vivax case-reporting data that could be obtained for all malaria endemic countries were used to classify risk into three classes: malaria free, unstable (<0.1 case per 1,000 people per annum (p.a.)) and stable (≥0.1 case per 1,000 p.a.),P. vivax malaria transmission.,Risk areas were further constrained using temperature and aridity data based upon their relationship with parasite and vector bionomics.,Medical intelligence was used to refine the spatial extent of risk in specific areas where transmission was reported to be absent (e.g., large urban areas and malaria-free islands).,The PAR under each level of transmission was then derived by combining the categorical risk map with a high resolution population surface adjusted to 2009.,The exclusion of large Duffy negative populations in Africa from the PAR totals was achieved using independent modelling of the gene frequency of this genetic trait.,It was estimated that 2.85 billion people were exposed to some risk of P. vivax transmission in 2009, with 57.1% of them living in areas of unstable transmission.,The vast majority (2.59 billion, 91.0%) were located in Central and South East (CSE) Asia, whilst the remainder were located in America (0.16 billion, 5.5%) and in the Africa+ region (0.10 billion, 3.5%).,Despite evidence of ubiquitous risk of P. vivax infection in Africa, the very high prevalence of Duffy negativity throughout Central and West Africa reduced the PAR estimates substantially.,After more than a century of development and control, P. vivax remains more widely distributed than P. falciparum and is a potential cause of morbidity and mortality amongst the 2.85 billion people living at risk of infection, the majority of whom are in the tropical belt of CSE Asia.,The probability of infection is reduced massively across Africa by the frequency of the Duffy negative trait, but transmission does occur on the continent and is a concern for Duffy positive locals and travellers.,The final map provides the spatial limits on which the endemicity of P. vivax transmission can be mapped to support future cartographic-based burden estimations.

Objective To examine the impact of providing rapid diagnostic tests for malaria on fever management in private drug retail shops where most poor rural people with fever present, with the aim of reducing current massive overdiagnosis and overtreatment of malaria.,Design Cluster randomized trial of 24 clusters of shops.,Setting Dangme West, a poor rural district of Ghana.,Participants Shops and their clients, both adults and children.,Interventions Providing rapid diagnostic tests with realistic training.,Main outcome measures The primary outcome was the proportion of clients testing negative for malaria by a double-read research blood slide who received an artemisinin combination therapy or other antimalarial.,Secondary outcomes were use of antibiotics and antipyretics, and safety.,Results Of 4603 clients, 3424 (74.4%) tested negative by double-read research slides.,The proportion of slide-negative clients who received any antimalarial was 590/1854 (32%) in the intervention arm and 1378/1570 (88%) in the control arm (adjusted risk ratio 0.41 (95% CI 0.29 to 0.58), P<0.0001).,Treatment was in high agreement with rapid diagnostic test result.,Of those who were slide-positive, 690/787 (87.8%) in the intervention arm and 347/392 (88.5%) in the control arm received an artemisinin combination therapy (adjusted risk ratio 0.96 (0.84 to 1.09)).,There was no evidence of antibiotics being substituted for antimalarials.,Overall, 1954/2641 (74%) clients in the intervention arm and 539/1962 (27%) in the control arm received appropriate treatment (adjusted risk ratio 2.39 (1.69 to 3.39), P<0.0001).,No safety concerns were identified.,Conclusions Most patients with fever in Africa present to the private sector.,In this trial, providing rapid diagnostic tests for malaria in the private drug retail sector significantly reduced dispensing of antimalarials to patients without malaria, did not reduce prescribing of antimalarials to true malaria cases, and appeared safe.,Rapid diagnostic tests should be considered for the informal private drug retail sector.,Registration Clinicaltrials.gov NCT01907672

The debate on rapid diagnostic tests (RDTs) for malaria has begun to shift from whether RDTs should be used, to how and under what circumstances their use can be optimized.,This has increased the need for a better understanding of the complexities surrounding the role of RDTs in appropriate treatment of fever.,Studies have focused on clinician practices, but few have sought to understand patient perspectives, beyond notions of acceptability.,This qualitative study aimed to explore patient and caregiver perceptions and experiences of RDTs following a trial to assess the introduction of the tests into routine clinical care at four health facilities in one district in Ghana.,Six focus group discussions and one in-depth interview were carried out with those who had received an RDT with a negative test result.,Patients had high expectations of RDTs.,They welcomed the tests as aiding clinical diagnoses and as tools that could communicate their problem better than they could, verbally.,However, respondents also believed the tests could identify any cause of illness, beyond malaria.,Experiences of patients suggested that RDTs were adopted into an existing system where patients are both physically and intellectually removed from diagnostic processes and where clinicians retain authority that supersedes tests and their results.,In this situation, patients did not feel able to articulate a demand for test-driven diagnosis.,Improvements in communication between the health worker and patient, particularly to explain the capabilities of the test and management of RDT negative cases, may both manage patient expectations and promote patient demand for test-driven diagnoses.

There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance.,We describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the parasite, with good pharmacokinetic properties, and an acceptable safety profile.,DDD107498 demonstrates potential to address a variety of clinical needs, including single dose treatment, transmission blocking and chemoprotection.,DDD107498 was developed from a screening programme against blood stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along mRNA, and is essential for protein synthesis.,This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery.

Vaccines that interrupt malaria transmission are of increasing interest and a robust functional assay to measure this activity would promote their development by providing a biologically relevant means of evaluating potential vaccine candidates.,Therefore, we aimed to qualify the standard membrane-feeding assay (SMFA).,The assay measures the transmission-blocking activity of antibodies by feeding cultured P. falciparum gametocytes to Anopheles mosquitoes in the presence of the test antibodies and measuring subsequent mosquito infection.,The International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline Q2(R1) details characteristics considered in assay validation.,Of these characteristics, we decided to qualify the SMFA for Precision, Linearity, Range and Specificity.,The transmission-blocking 4B7 monoclonal antibody was tested over 6 feeding experiments at several concentrations to determine four suitable concentrations that were tested in triplicate in the qualification experiments (3 additional feeds) to evaluate Precision, Linearity and Range.,For Specificity, 4B7 was tested in the presence of normal mouse IgG.,We determined intra- and inter-assay variability of % inhibition of mean oocyst intensity at each concentration of 4B7 (lower concentrations showed higher variability).,We also showed that % inhibition was dependent on 4B7 concentration and the activity is specific to 4B7.,Since obtaining empirical data is time-consuming, we generated a model using data from all 9 feeds and simulated the effects of different parameters on final readouts to improve the assay procedure and analytical methods for future studies.,For example, we estimated the effect of number of mosquitoes dissected on variability of % inhibition, and simulated the relationship between % inhibition in oocyst intensity and % inhibition of prevalence of infected mosquitos at different mean oocysts in the control.,SMFA is one of the few biological assays used in preclinical and early clinical development of transmission-blocking vaccines, and this study strongly supports its further development and application.

Intermittent preventive treatment could help prevent malaria in infants (IPTi) living in areas of moderate to high malaria transmission in sub‐Saharan Africa.,The World Health Organization (WHO) policy recommended IPTi in 2010, but its adoption in countries has been limited.,To evaluate the effects of intermittent preventive treatment (IPT) with antimalarial drugs to prevent malaria in infants living in malaria‐endemic areas.,We searched the following sources up to 3 December 2018: the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (the Cochrane Library), MEDLINE (PubMed), Embase (OVID), LILACS (Bireme), and reference lists of articles.,We also searched the metaRegister of Controlled Trials (mRCT) and the WHO International Clinical Trials Registry Platform (ICTRP) portal for ongoing trials up to 3 December 2018.,We included randomized controlled trials (RCTs) that compared IPT to placebo or no intervention in infants (defined as young children aged between 1 to 12 months) in malaria‐endemic areas.,The primary outcome was clinical malaria (fever plus asexual parasitaemia).,Two review authors independently assessed trials for inclusion, evaluated the risk of bias, and extracted data.,We summarized dichotomous outcomes and count data using risk ratios (RR) and rate ratios respectively, and presented all measures with 95% confidence intervals (CIs).,We extracted protective efficacy values and their 95% CIs; when an included trial did not report this data, we calculated these values from the RR or rate ratio with its 95% CI.,Where appropriate, we combined data in meta‐analyses and assessed the certainty of the evidence using the GRADE approach.,We included 12 trials that enrolled 19,098 infants; all were conducted in sub‐Saharan Africa.,Three trials were cluster‐RCTs.,IPTi with sulfadoxine‐pyrimethamine (SP) was evaluated in 10 trials from 1999 to 2013 (n = 15,256).,Trials evaluating ACTs included dihydroartemisinin‐piperaquine (1 trial, 147 participants; year 2013), amodiaquine‐artesunate (1 study, 684 participants; year 2008), and SP‐artesunate (1 trial, 676 participants; year 2008).,The earlier studies evaluated IPTi with SP, and were conducted in Tanzania (in 1999 and 2006), Mozambique (2004), Ghana (2004 to 2005), Gabon (2005), Kenya (2008), and Mali (2009).,One trial evaluated IPTi with amodiaquine in Tanzania (2000).,Later studies included three conducted in Kenya (2008), Tanzania (2008), and Uganda (2013), evaluating IPTi in multiple trial arms that included artemisinin‐based combination therapy (ACT).,Although the effect size varied over time and between drugs, overall IPTi impacts on the incidence of clinical malaria overall, with a 27% reduction (rate ratio 0.73, 0.65 to 0.82; 10 studies, 10,602 participants).,The effect of SP appeared to attenuate over time, with trials conducted after 2009 showing little or no effect of the intervention.,IPTi with SP probably resulted in fewer episodes of clinical malaria (rate ratio 0.79, 0.74 to 0.85; 8 trials, 8774 participants, moderate‐certainty evidence), anaemia (rate ratio 0.82, 0.68 to 0.98; 6 trials, 7438 participants, moderate‐certainty evidence), parasitaemia (rate ratio 0.66, 0.56 to 0.79; 1 trial, 1200 participants, moderate‐certainty evidence), and fewer hospital admissions (rate ratio 0.85, 0.78 to 0.93; 7 trials, 7486 participants, moderate‐certainty evidence).,IPTi with SP probably made little or no difference to all‐cause mortality (risk ratio 0.93, 0.74 to 1.15; 9 trials, 14,588 participants, moderate‐certainty evidence).,Since 2009, IPTi trials have evaluated ACTs and indicate impact on clinical malaria and parasitaemia.,A small trial of DHAP in 2013 shows substantive effects on clinical malaria (RR 0.42, 0.33 to 0.54; 1 trial, 147 participants, moderate‐certainty evidence) and parasitaemia (moderate‐certainty evidence).,In areas of sub‐Saharan Africa, giving antimalarial drugs known to be effective against the malaria parasite at the time to infants as IPT probably reduces the risk of clinical malaria, anaemia, and hospital admission.,Evidence from SP studies over a 19‐year period shows declining efficacy, which may be due to increasing drug resistance.,Combinations with ACTs appear promising as suitable alternatives for IPTi.,2 December 2019,Up to date,All studies incorporated from most recent search,All eligible published studies found in the last search (3 Dec, 2018) were included,Administering antimalarial drugs to prevent malaria in infants,What is the aim of the review?,This Cochrane Review aimed to find out if administering repeated doses of antimalarial treatment to infants living in sub‐Saharan Africa can prevent malaria.,We found and analysed results from 12 relevant studies conducted between 1999 and 2013 that addressed this question in infants (defined as young children aged between 1 to 12 months).,Key messages,Intermittent preventive treatment with sulfadoxine‐pyrimethamine (SP),Giving SP as preventive antimalarial treatment to infants probably reduced the risk of clinical malaria, anaemia, and hospital admissions in the African countries it was evaluated.,However, this effect was attenuated in more recent studies.,Intermittent preventive treatment with artemisinin‐based combination therapy (ACT),Giving ACT as preventive antimalarial treatment to infants may reduce the risk of clinical malaria.,It may also reduce the proportion of infants with malaria parasites in their blood.,What was studied in the review?,In areas where malaria is common, infants often suffer repeated episodes of malarial illness.,In areas where malaria transmission occurs all‐year, some authorities recommend intermittent preventive treatment, which requires giving drugs at regular intervals (at child vaccination visits) regardless of whether the child has malaria symptoms or not to prevent malarial illness.,We studied the effects of IPTi with SP and other medicines (including ACTs) on malaria‐related outcomes.,Review outcomes included clinical malaria, severe malaria, death, hospital admission, parasitaemia, anaemia, change in haemoglobin level, and side effects.,What are the main results of the review?,We included 12 studies that enrolled 19,098 infants.,All studies were done in sub‐Saharan Africa (Gabon, Ghana, Kenya, Mali, Mozambique, Tanzania, and Uganda).,These studies compared infants who received IPTi to those who received placebo pills or nothing.,The infants in the IPTi group were given different medicines, in different doses, and for different lengths of time.,Ten studies evaluated IPTi with SP from 1999 to 2013.,The effect of SP appear to wane over time, with trials conducted after 2009 showing little or no effect of the intervention.,The studies show that IPTi with SP probably resulted in fewer episodes of clinical malaria, anaemia, hospital admission, and blood parasites without symptoms (moderate‐certainty evidence).,IPTi with SP probably made little or no difference to the risk of death (moderate‐certainty evidence).,Since 2009, IPTi some small studies have evaluated artemisinin‐based combination medicines and indicate impact on clinical malaria and blood parasites.,A small study of IPTi with dihydroartemisinin‐piperaquine in 2013 showed up to 58% reduction in episodes of clinical malaria (moderate‐certainty evidence) and reductions in proportion of infants with blood parasites (moderate‐certainty evidence).,How up‐to‐date is this review?,The review authors searched for studies published up to 3 December 2018.

Mass anti-malarial administration has been proposed as a key component of the Plasmodium falciparum malaria elimination strategy in the Greater Mekong sub-Region.,Its effectiveness depends on high levels of coverage in the target population.,This article explores the factors that influenced mass anti-malarial administration coverage within a clinical trial in Battambang Province, western Cambodia.,Qualitative data were collected through semi-structured interviews and focus group discussions with villagers, in-depth interviews with study staff, trial drop-outs and refusers, and observations in the communities.,Interviews were audio-recorded, transcribed and translated from Khmer to English for qualitative content analysis using QSR NVivo.,Malaria was an important health concern and villagers reported a demand for malaria treatment.,This was in spite of a fall in incidence over the previous decade and a lack of familiarity with asymptomatic malaria.,Participants generally understood the overall study aim and were familiar with study activities.,Comprehension of the study rationale was however limited.,After the first mass anti-malarial administration, seasonal health complaints that participants attributed to the anti-malarial as “side effects” contributed to a decrease of coverage in round two.,Staff therefore adapted the community engagement approach, bringing to prominence local leaders in village meetings.,This contributed to a subsequent increase in coverage.,Future mass anti-malarial administration must consider seasonal disease patterns and the importance of local leaders taking prominent roles in community engagement.,Further research is needed to investigate coverage in scenarios that more closely resemble implementation i.e. without participation incentives, blood sampling and free healthcare.

No investigations have been undertaken of risk factors for intensity of soil-transmitted helminth (STH) infection in Timor-Leste.,This study provides the first analysis of risk factors for intensity of STH infection, as determined by quantitative PCR (qPCR), examining a broad range of water, sanitation and hygiene (WASH) and environmental factors, among communities in Manufahi District, Timor-Leste.,A baseline cross-sectional survey of 18 communities was undertaken as part of a cluster randomised controlled trial, with additional identically-collected data from six other communities. qPCR was used to assess STH infection from stool samples, and questionnaires administered to collect WASH, demographic, and socioeconomic data.,Environmental information was obtained from open-access sources and linked to infection outcomes.,Mixed-effects multinomial logistic regression was undertaken to assess risk factors for intensity of Necator americanus and Ascaris infection.,2152 participants provided stool and questionnaire information for this analysis.,In adjusted models incorporating WASH, demographic and environmental variables, environmental variables were generally associated with infection intensity for both N. americanus and Ascaris spp.,Precipitation (in centimetres) was associated with increased risk of moderate-intensity (adjusted relative risk [ARR] 6.1; 95% confidence interval [CI] 1.9-19.3) and heavy-intensity (ARR 6.6; 95% CI 3.1-14.1) N. americanus infection, as was sandy-loam soil around households (moderate-intensity ARR 2.1; 95% CI 1.0-4.3; heavy-intensity ARR 2.7; 95% CI 1.6-4.5; compared to no infection).,For Ascaris, alkaline soil around the household was associated with reduced risk of moderate-intensity infection (ARR 0.21; 95% CI 0.09-0.51), and heavy-intensity infection (ARR 0.04; 95% CI 0.01-0.25).,Few WASH risk factors were significant.,In this high-prevalence setting, strong risk associations with environmental factors indicate that anthelmintic treatment alone will be insufficient to interrupt STH transmission, as conditions are favourable for ongoing environmental transmission.,Integrated STH control strategies should be explored as a priority.

In Brazil, preventive chemotherapy targeting soil-transmitted helminthiasis is being scaled-up.,Hence, spatially explicit estimates of infection risks providing information about the current situation are needed to guide interventions.,Available high-resolution national model-based estimates either rely on analyses of data restricted to a given period of time, or on historical data collected over a longer period.,While efforts have been made to take into account the spatial structure of the data in the modelling approach, little emphasis has been placed on the temporal dimension.,We extracted georeferenced survey data on the prevalence of infection with soil-transmitted helminths (i.e.,Ascaris lumbricoides, hookworm and Trichuris trichiura) in Brazil from the Global Neglected Tropical Diseases (GNTD) database.,Selection of the most important predictors of infection risk was carried out using a Bayesian geostatistical approach and temporal models that address non-linearity and correlation of the explanatory variables.,The spatial process was estimated through a predictive process approximation.,Spatio-temporal models were built on the selected predictors with integrated nested Laplace approximation using stochastic partial differential equations.,Our models revealed that, over the past 20 years, the risk of soil-transmitted helminth infection has decreased in Brazil, mainly because of the reduction of A. lumbricoides and hookworm infections.,From 2010 onwards, we estimate that the infection prevalences with A. lumbricoides, hookworm and T. trichiura are 3.6%, 1.7% and 1.4%, respectively.,We also provide a map highlighting municipalities in need of preventive chemotherapy, based on a predicted soil-transmitted helminth infection risk in excess of 20%.,The need for treatments in the school-aged population at the municipality level was estimated at 1.8 million doses of anthelminthic tablets per year.,The analysis of the spatio-temporal aspect of the risk of infection with soil-transmitted helminths contributes to a better understanding of the evolution of risk over time.,Risk estimates provide the soil-transmitted helminthiasis control programme in Brazil with useful benchmark information for prioritising and improving spatial and temporal targeting of interventions.,The online version of this article (doi:10.1186/1756-3305-7-440) contains supplementary material, which is available to authorized users.

The most widespread Plasmodium species, Plasmodium vivax, poses a significant public health threat.,An effective vaccine is needed to reduce global malaria burden.,Of the erythrocytic stage vaccine candidates, the 19 kDa fragment of the P. vivax Merozoite Surface Protein 1 (PvMSP119) is one of the most promising.,Our group has previously defined several promiscuous T helper epitopes within the PvMSP1 protein, with features that allow them to bind multiple MHC class II alleles.,We describe here a P. vivax recombinant modular chimera based on MSP1 (PvRMC-MSP1) that includes defined T cell epitopes genetically fused to PvMSP119.,This vaccine candidate preserved structural elements of the native PvMSP119 and elicited cytophilic antibody responses, and CD4+ and CD8+ T cells capable of recognizing PvMSP119.,Although CD8+ T cells that recognize blood stage antigens have been reported to control blood infection, CD8+ T cell responses induced by P. falciparum or P. vivax vaccine candidates based on MSP119 have not been reported.,To our knowledge, this is the first time a protein based subunit vaccine has been able to induce CD8+ T cell against PvMSP119.,The PvRMC-MSP1 protein was also recognized by naturally acquired antibodies from individuals living in malaria endemic areas with an antibody profile associated with protection from infection.,These features make PvRMC-MSP1 a promising vaccine candidate.

With renewed interest in malaria elimination, island environments present unique opportunities to achieve this goal.,However, as transmission decreases, monitoring and evaluation programmes need increasingly sensitive tools to assess Plasmodium falciparum and Plasmodium vivax exposure.,In 2009, to assess the role of serological markers in evaluating malaria transmission, a cross-sectional seroprevalence study was carried out in Tanna and Aneityum, two of the southernmost islands of the Vanuatu archipelago, areas where malaria transmission has been variably reduced over the past few decades.,Malaria transmission was assessed using serological markers for exposure to P. falciparum and P. vivax.,Filter blood spot papers were collected from 1,249 people from Tanna, and 517 people from Aneityum to assess the prevalence of antibodies to two P. falciparum antigens (MSP-119 and AMA-1) and two P. vivax antigens (MSP-119 and AMA-1).,Age-specific prevalence was modelled using a simple catalytic conversion model based on maximum likelihood to generate a community seroconversion rate (SCR).,Overall seropositivity in Tanna was 9.4%, 12.4% and 16.6% to P. falciparum MSP-119, AMA-1 and Schizont Extract respectively and 12.6% and 15.0% to P. vivax MSP-119 and AMA-1 respectively.,Serological results distinguished between areas of differential dominance of either P. vivax or P. falciparum and analysis of age-stratified results showed a step in seroprevalence occurring approximately 30 years ago on both islands, indicative of a change in transmission intensity at this time.,Results from Aneityum suggest that several children may have been exposed to malaria since the 2002 P. vivax epidemic.,Seroepidemiology can provide key information on malaria transmission for control programmes, when parasite rates are low.,As Vanuatu moves closer to malaria elimination, monitoring changes in transmission intensity and identification of residual malaria foci is paramount in order to concentrate intervention efforts.

Host and parasite diversity are suspected to be key factors in Chagas disease pathogenesis.,Experimental investigation of underlying mechanisms is hampered by a lack of tools to detect scarce, pleiotropic infection foci.,We developed sensitive imaging models to track Trypanosoma cruzi infection dynamics and quantify tissue‐specific parasite loads, with minimal sampling bias.,We used this technology to investigate cardiomyopathy caused by highly divergent parasite strains in BALB/c, C3H/HeN and C57BL/6 mice.,The gastrointestinal tract was unexpectedly found to be the primary site of chronic infection in all models.,Immunosuppression induced expansion of parasite loads in the gut and was followed by widespread dissemination.,These data indicate that differential immune control of T. cruzi occurs between tissues and shows that the large intestine and stomach provide permissive niches for active infection.,The end‐point frequency of heart‐specific infections ranged from 0% in TcVI‐CLBR‐infected C57BL/6 to 88% in TcI‐JR‐infected C3H/HeN mice.,Nevertheless, infection led to fibrotic cardiac pathology in all models.,Heart disease severity was associated with the model‐dependent frequency of dissemination outside the gut and inferred cumulative heart‐specific parasite loads.,We propose a model of cardiac pathogenesis driven by periodic trafficking of parasites into the heart, occurring at a frequency determined by host and parasite genetics.

Chronic Trypanosoma cruzi infections lead to cardiomyopathy in 20-30% of cases.,A causal link between cardiac infection and pathology has been difficult to establish because of a lack of robust methods to detect scarce, focally distributed parasites within tissues.,We developed a highly sensitive bioluminescence imaging system based on T. cruzi expressing a novel luciferase that emits tissue-penetrating orange-red light.,This enabled long-term serial evaluation of parasite burdens in individual mice with an in vivo limit of detection of significantly less than 1000 parasites.,Parasite distributions during chronic infections were highly focal and spatiotemporally dynamic, but did not localize to the heart.,End-point ex vivo bioluminescence imaging allowed tissue-specific quantification of parasite loads with minimal sampling bias.,During chronic infections, the gastro-intestinal tract, specifically the colon and stomach, was the only site where T. cruzi infection was consistently observed.,Quantitative PCR-inferred parasite loads correlated with ex vivo bioluminescence and confirmed the gut as the parasite reservoir.,Chronically infected mice developed myocarditis and cardiac fibrosis, despite the absence of locally persistent parasites.,These data identify the gut as a permissive niche for long-term T. cruzi infection and show that canonical features of Chagas disease can occur without continual myocardium-specific infection.

Suman Rijal and colleagues highlight lessons from a regional collaboration to eliminate visceral leishmaniasis and identify priorities for the post-elimination plan

Immunochromatographic tests based on the recombinant antigen K39 represent a major advance in diagnosing visceral leishmaniasis (VL) in recent years.,Some performance variations are expected and have occurred in the use of several commercial rapid tests, especially in different geographical settings.,This is the first evaluation in the Americas of the test recently provided by the public health system in Brazil for the diagnostic of VL, the OnSite™ Leishmania IgG/IgM Combo.,In this first clinical test evaluation, 113 VL-positive patient samples and 73 negative controls were tested and a sensitivity of 91.2% and specificity of 94.5% were observed.,These results indicate the need for further analysis and comparisons with the performance of other available commercial tests in order to define the impact of this new test on the quality of VL diagnosis in Brazil.

Our understanding of the structure and regulation of Plasmodium vivax genes is limited by our inability to grow the parasites in long-term in vitro cultures.,Most P. vivax studies must therefore rely on patient samples, which typically display a low proportion of parasites and asynchronous parasites.,Here, we present stranded RNA-seq data generated directly from a small volume of blood from three Cambodian vivax malaria patients collected before treatment.,Our analyses show surprising similarities of the parasite gene expression patterns across infections, despite extensive variations in parasite stage proportion.,These similarities contrast with the unique gene expression patterns observed in sporozoites isolated from salivary glands of infected Colombian mosquitoes.,Our analyses also indicate that more than 10% of P. vivax genes encode multiple, often undescribed, protein-coding sequences, potentially increasing the diversity of proteins synthesized by blood stage parasites.,These data also greatly improve the annotations of P. vivax gene untranslated regions, providing an important resource for future studies of specific genes.

A research priority for Plasmodium vivax malaria is to improve our understanding of the spatial distribution of risk and its relationship with the burden of P. vivax disease in human populations.,The aim of the research outlined in this article is to provide a contemporary evidence-based map of the global spatial extent of P. vivax malaria, together with estimates of the human population at risk (PAR) of any level of transmission in 2009.,The most recent P. vivax case-reporting data that could be obtained for all malaria endemic countries were used to classify risk into three classes: malaria free, unstable (<0.1 case per 1,000 people per annum (p.a.)) and stable (≥0.1 case per 1,000 p.a.),P. vivax malaria transmission.,Risk areas were further constrained using temperature and aridity data based upon their relationship with parasite and vector bionomics.,Medical intelligence was used to refine the spatial extent of risk in specific areas where transmission was reported to be absent (e.g., large urban areas and malaria-free islands).,The PAR under each level of transmission was then derived by combining the categorical risk map with a high resolution population surface adjusted to 2009.,The exclusion of large Duffy negative populations in Africa from the PAR totals was achieved using independent modelling of the gene frequency of this genetic trait.,It was estimated that 2.85 billion people were exposed to some risk of P. vivax transmission in 2009, with 57.1% of them living in areas of unstable transmission.,The vast majority (2.59 billion, 91.0%) were located in Central and South East (CSE) Asia, whilst the remainder were located in America (0.16 billion, 5.5%) and in the Africa+ region (0.10 billion, 3.5%).,Despite evidence of ubiquitous risk of P. vivax infection in Africa, the very high prevalence of Duffy negativity throughout Central and West Africa reduced the PAR estimates substantially.,After more than a century of development and control, P. vivax remains more widely distributed than P. falciparum and is a potential cause of morbidity and mortality amongst the 2.85 billion people living at risk of infection, the majority of whom are in the tropical belt of CSE Asia.,The probability of infection is reduced massively across Africa by the frequency of the Duffy negative trait, but transmission does occur on the continent and is a concern for Duffy positive locals and travellers.,The final map provides the spatial limits on which the endemicity of P. vivax transmission can be mapped to support future cartographic-based burden estimations.

Malaria has been responsible for the highest mortality in most malaria endemic countries.,Even after decades of malaria control campaigns, it still persists as a disease of high mortality due to improper diagnosis and rapidly evolving drug resistant malarial parasites.,For efficient and economical malaria management, WHO recommends that all malaria suspected patients should receive proper diagnosis before administering drugs.,It is thus imperative to develop fast, economical, and accurate techniques for diagnosis of malaria.,In this regard an in-depth knowledge on malaria biomarkers is important to identify an appropriate biorecognition element and utilize it prudently to develop a reliable detection technique for diagnosis of the disease.,Among the various biomarkers, plasmodial lactate dehydrogenase and histidine-rich protein II (HRP II) have received increasing attention for developing rapid and reliable detection techniques for malaria.,The widely used rapid detection tests (RDTs) for malaria succumb to many drawbacks which promotes exploration of more efficient economical detection techniques.,This paper provides an overview on the current status of malaria biomarkers, along with their potential utilization for developing different malaria diagnostic techniques and advanced biosensors.

The need to develop new methods for the high-sensitivity diagnosis of malaria has initiated a global activity in medical and interdisciplinary sciences.,Most of the diverse variety of emerging techniques are based on research-grade instruments, sophisticated reagent-based assays or rely on expertise.,Here, we suggest an alternative optical methodology with an easy-to-use and cost-effective instrumentation based on unique properties of malaria pigment reported previously and determined quantitatively in the present study.,Malaria pigment, also called hemozoin, is an insoluble microcrystalline form of heme.,These crystallites show remarkable magnetic and optical anisotropy distinctly from any other components of blood.,As a consequence, they can simultaneously act as magnetically driven micro-rotors and spinning polarizers in suspensions.,These properties can gain importance not only in malaria diagnosis and therapies, where hemozoin is considered as drug target or immune modulator, but also in the magnetic manipulation of cells and tissues on the microscopic scale.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was created in 2008 to answer questions of importance to program managers working to reduce the burden of schistosomiasis in Africa.,In the past, intermediate host snail monitoring and control was an important part of integrated schistosomiasis control.,However, in Africa, efforts to control snails have declined dramatically over the last 30 years.,A resurgence of interest in the control of snails has been prompted by the realization, backed by a World Health Assembly resolution (WHA65.21), that mass drug administration alone may be insufficient to achieve schistosomiasis elimination.,SCORE has supported work on snail identification and mapping and investigated how xenomonitoring techniques can aid in the identification of infected snails and thereby identify potential transmission areas.,Focal mollusciciding with niclosamide was undertaken in Zanzibar and Côte d’Ivoire as a part of elimination studies.,Two studies involving biological control of snails were conducted: one explored the association of freshwater riverine prawns and snail hosts in Côte d’Ivoire and the other assessed the current distribution of Procambarus clarkii, the invasive Louisiana red swamp crayfish, in Kenya and its association with snail hosts and schistosomiasis transmission.,SCORE also supported modeling studies on the importance of snail control in achieving elimination and a meta-analysis of the impact of molluscicide-based snail control programs on human schistosomiasis prevalence and incidence.,SCORE’s snail control studies contributed to increased investment in building capacity, and specimens collected during SCORE research deposited in the Schistosomiasis Collections at the Natural History Museum (SCAN) will provide a valuable resource for the years to come.

Programs for schistosomiasis control are advancing worldwide, with many benefits noted in terms of disease reduction.,Yet risk of reinfection and recurrent disease remain, even in areas with high treatment coverage.,In the search for means to better prevent new Schistosoma infections, attention has returned to an older strategy for transmission control, i.e., chemical mollusciciding, to suppress intermediate host snail species responsible for S. mansoni and S. haematobium transmission.,The objective of this systematic review and meta-analysis was to summarize prior experience in molluscicide-based control of Bulinus and Biomphalaria spp. snails, and estimate its impact on local human Schistosoma infection.,The review was registered at inception with PROSPERO (CRD42013006869).,Studies were identified by online database searches and hand searches of private archives.,Eligible studies included published or unpublished mollusciciding field trials performed before January 2014 involving host snails for S. mansoni or S. haematobium, with a primary focus on the use of niclosamide.,Among 63 included papers, there was large variability in terms of molluscicide dosing, and treatment intervals varied from 3-52 weeks depending on location, water source, and type of application.,Among 35 studies reporting on prevalence, random effects meta-analysis indicated that, on average, odds of infection were reduced 77% (OR 0.23, CI95% 0.17, 0.31) during the course of mollusciciding, with increased impact if combined with drug therapy, and progressively greater impact over time.,In 17 studies reporting local incidence, risk of new infection was reduced 64% (RR 0.36 CI95% 0.25, 0.5), but additional drug treatment did not appear to influence incidence effects.,While there are hurdles to implementing molluscicide control, its impact on local transmission is typically strong, albeit incomplete.,Based on past experience, regular focal mollusciciding is likely to contribute significantly to the move toward elimination of schistosomiasis in high risk areas.

Human whipworm (Trichuris trichiura) infects approximately 1 in 15 people worldwide, representing the leading infectious cause of colitis and subsequent, inflammatory bowel disease (IBD).,Current control measures focused on mass deworming have had limited success due to low drug efficacies.,Vaccination would be an ideal, cost-effective strategy to induce protective immunity, leading to control of infection and transmission.,Here we report the identification of whey acidic protein, a whipworm secretory protein, as a strong immunogen for inducing protective efficacy in a surrogate mouse T. muris infection model.,The recombinant WAP protein (rTm-WAP49), as well as a single, highly conserved repeat within WAP (fragment 8) expressed as an Na-GST-1 fusion protein (rTm-WAP-F8+Na-GST-1), generate a strong T helper type 2 (Th2) immune response when delivered as subcutaneous vaccines formulated with Montanide ISA 720.,Oral challenge with T. muris infective eggs following vaccination led to a significant reduction in worm burden of 48% by rTm-WAP49 and 33% by rTm-WAP-F8+Na-GST-1.,The cellular immune correlates of protection included significant antigen-specific production of Th2 cytokines IL-4, IL-9, and IL-13 by cells isolated from the vaccine-draining inguinal lymph nodes, parasite-draining mesenteric lymph nodes, and spleen in mice vaccinated with either rTm-WAP49 or rTm-WAP-F8+Na-GST-1.,The humoral immune correlates included a high antigen-specific ratio of IgG1 to IgG2a, without eliciting an IgE-mediated allergic response.,Immunofluorescent staining of adult T. muris with WAP antisera identified the worm’s pathogenic stichosome organ as the site of secretion of native Tm-WAP protein into the colonic mucosa.,Given the high sequence conservation for the WAP proteins from T. muris and T. trichiura, the results presented here support the WAP protein to be further evaluated as a potential human whipworm vaccine candidate.

The helminth Ascaris causes ascariasis in both humans and pigs.,Humans, especially children, experience significant morbidity including respiratory complications, growth deficits and intestinal obstruction.,Given that 800 million people worldwide are infected by Ascaris, this represents a significant global public health concern.,The severity of the symptoms and associated morbidity are related to the parasite burden and not all hosts are infected equally.,While the pathology of the disease has been extensively examined, our understanding of the molecular mechanisms underlying resistance and susceptibility to this nematode infection is poor.,In order to investigate host differences associated with heavy and light parasite burden, an experimental murine model was developed utilising Ascaris-susceptible and -resistant mice strains, C57BL/6J and CBA/Ca, respectively, which experience differential burdens of migratory Ascaris larvae in the host lungs.,Previous studies identified the liver as the site where this difference in susceptibility occurs.,Using a label free quantitative proteomic approach, we analysed the hepatic proteomes of day four post infection C57BL/6J and CBA/Ca mice with and without Ascaris infection to identify proteins changes potentially linked to both resistance and susceptibility amongst the two strains, respectively.,Over 3000 proteins were identified in total and clear intrinsic differences were elucidated between the two strains.,These included a higher abundance of mitochondrial proteins, particularly those associated with the oxidative phosphorylation pathway and reactive oxygen species (ROS) production in the relatively resistant CBA/Ca mice.,We hypothesise that the increased ROS levels associated with higher levels of mitochondrial activity results in a highly oxidative cellular environment that has a dramatic effect on the nematode’s ability to successfully sustain a parasitic association with its resistant host.,Under infection, both strains had increased abundances in proteins associated with the oxidative phosphorylation pathway, as well as the tricarboxylic acid cycle, with respect to their controls, indicating a general stress response to Ascaris infection.,Despite the early stage of infection, some immune-associated proteins were identified to be differentially abundant, providing a novel insight into the host response to Ascaris.,In general, the susceptible C57BL/6J mice displayed higher abundances in immune-associated proteins, most likely signifying a more active nematode cohort with respect to their CBA/Ca counterparts.,The complement component C8a and S100 proteins, S100a8 and S100a9, were highly differentially abundant in both infected strains, signifying a potential innate immune response and the importance of the complement pathway in defence against macroparasite infection.,In addition, the signatures of an early adaptive immune response were observed through the presence of proteins, such as plastin-2 and dipeptidyl peptidase 1.,A marked decrease in proteins associated with translation was also observed in both C57BL/6J and CBA/Ca mice under infection, indicative of either a general response to Ascaris or a modulatory effect by the nematode itself.,Our research provides novel insights into the in vivo host-Ascaris relationship on the molecular level and provides new research perspectives in the development of Ascaris control and treatment strategies.

Current understanding of the spatial epidemiology and geographical distribution of Plasmodium vivax is far less developed than that for P. falciparum, representing a barrier to rational strategies for control and elimination.,Here we present the first systematic effort to map the global endemicity of this hitherto neglected parasite.,We first updated to the year 2010 our earlier estimate of the geographical limits of P. vivax transmission.,Within areas of stable transmission, an assembly of 9,970 geopositioned P. vivax parasite rate (PvPR) surveys collected from 1985 to 2010 were used with a spatiotemporal Bayesian model-based geostatistical approach to estimate endemicity age-standardised to the 1-99 year age range (PvPR1-99) within every 5×5 km resolution grid square.,The model incorporated data on Duffy negative phenotype frequency to suppress endemicity predictions, particularly in Africa.,Endemicity was predicted within a relatively narrow range throughout the endemic world, with the point estimate rarely exceeding 7% PvPR1-99.,The Americas contributed 22% of the global area at risk of P. vivax transmission, but high endemic areas were generally sparsely populated and the region contributed only 6% of the 2.5 billion people at risk (PAR) globally.,In Africa, Duffy negativity meant stable transmission was constrained to Madagascar and parts of the Horn, contributing 3.5% of global PAR.,Central Asia was home to 82% of global PAR with important high endemic areas coinciding with dense populations particularly in India and Myanmar.,South East Asia contained areas of the highest endemicity in Indonesia and Papua New Guinea and contributed 9% of global PAR.,This detailed depiction of spatially varying endemicity is intended to contribute to a much-needed paradigm shift towards geographically stratified and evidence-based planning for P. vivax control and elimination.

Severe outcomes have been described for both Plasmodium falciparum and P. vivax infections.,The identification of sensitive and reliable markers of disease severity is fundamental to improving patient care.,An intense pro-inflammatory response with oxidative stress and production of reactive oxygen species is present in malaria.,Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and antioxidant agents such as superoxide dismutase-1 (SOD-1) are likely candidate biomarkers for disease severity.,Here we tested whether plasma levels of SOD-1 could serve as a biomarker of severe vivax malaria.,Plasma samples were obtained from residents of the Brazilian Amazon with a high risk for P. vivax transmission.,Malaria diagnosis was made by both microscopy and nested PCR.,A total of 219 individuals were enrolled: non-infected volunteers (n = 90) and individuals with vivax malaria: asymptomatic (n = 60), mild (n = 50) and severe infection (n = 19).,SOD-1 was directly associated with parasitaemia, plasma creatinine and alanine amino-transaminase levels, while TNF-alpha correlated only with the later enzyme.,The predictive power of SOD-1 and TNF-alpha levels was compared.,SOD-1 protein levels were more effective at predicting vivax malaria severity than TNF-alpha.,For discrimination of mild infection, elevated SOD-1 levels showed greater sensitivity than TNF-alpha (76% vs. 30% respectively; p<0.0001), with higher specificity (100% vs. 97%; p<0.0001).,In predicting severe vivax malaria, SOD-1 levels exhibited higher sensitivity than TNF-alpha (80% vs. 56%, respectively; p<0.0001; likelihood ratio: 7.45 vs.,3.14; p<0.0001).,Neither SOD-1 nor TNF-alpha could discriminate P. vivax infections from those caused by P. falciparum.,SOD-1 is a powerful predictor of disease severity in individuals with different clinical presentations of vivax malaria.

The widespread presence of low-density asymptomatic infections with concurrent gametocytes may be a stumbling block for malaria elimination.,This study investigated the asymptomatic reservoir of Plasmodium falciparum and Plasmodium vivax infections in schoolchildren from five settings in northwest Ethiopia.,Two cross-sectional surveys were conducted in June and November 2015, enrolling 551 students from five schools and 294 students from three schools, respectively.,Finger prick whole blood and plasma samples were collected.,The prevalence and density of P. falciparum and P. vivax parasitaemia and gametocytaemia were determined by 18S rRNA quantitative PCR (qPCR) and pfs25 and pvs25 reverse transcriptase qPCR.,Antibodies against blood stage antigens apical membrane antigen-1 (AMA-1) and merozoite surface protein-1 (MSP-119) were measured for both species.,Whilst only 6 infections were detected by microscopy in 881 slides (0.7%), 107 of 845 blood samples (12.7%) were parasite positive by (DNA-based) qPCR. qPCR parasite prevalence between sites and surveys ranged from 3.8 to 19.0% for P. falciparum and 0.0 to 9.0% for P. vivax.,The median density of P. falciparum infections (n = 85) was 24.4 parasites/µL (IQR 18.0-34.0) and the median density of P. vivax infections (n = 28) was 16.4 parasites/µL (IQR 8.8-55.1).,Gametocyte densities by (mRNA-based) qRT-PCR were strongly associated with total parasite densities for both P. falciparum (correlation coefficient = 0.83, p = 0.010) and P. vivax (correlation coefficient = 0.58, p = 0.010).,Antibody titers against P. falciparum AMA-1 and MSP-119 were higher in individuals who were P. falciparum parasite positive in both surveys (p < 0.001 for both comparisons).,This study adds to the available evidence on the wide-scale presence of submicroscopic parasitaemia by quantifying submicroscopic parasite densities and concurrent gametocyte densities.,There was considerable heterogeneity in the occurrence of P. falciparum and P. vivax infections and serological markers of parasite exposure between the examined low endemic settings in Ethiopia.

Asymptomatic, low parasite density malaria infections are difficult to detect with currently available point-of-care diagnostics.,This study piloted a loop-mediated isothermal amplification (LAMP) kit for field-friendly, high-throughput detection of asymptomatic malaria infections during mass screening and treatment (MSAT) in Zanzibar, a malaria pre-elimination setting.,Screening took place in three known hotspot areas prior to the short rains in November.,Finger-prick blood was taken for screening by rapid diagnostic test (RDT) and LAMP and collected on filter paper for subsequent polymerase chain reaction (PCR) analyses.,LAMP results were compared to RDT and to PCR using McNemar’s test.,Approximately 1,000 people were screened.,RDT detected ten infections (1.0% (95% CI 0.3-1.6)) whilst both LAMP and PCR detected 18 (1.8% (95% CI 0.9-2.6)) infections.,However, PCR identified three infections that LAMP did not detect and vice versa.,LAMP testing was easy to scale-up in field conditions requiring minimal training and equipment, with results ready one to three hours after screening.,Despite lower than expected prevalence, LAMP detected a higher number of infections than the currently used diagnostic, RDT.,LAMP is a field-friendly, sensitive diagnostic test that could be useful for MSAT malaria campaigns which require quick results to enable prompt treatment.

Epigenetic changes in response to allergen exposure are still not well understood.,The aim of this study was to evaluate histone acetylation levels in peripheral blood leukocytes from humans naturally infected by intestinal parasites and perennially exposed to house dust mites (HDM).,Peripheral blood mononuclear cells (PBMCs) were isolated by gradient centrifugation from 20 infected and 21 non-infected individuals living in a rural/village in Colombia.,Histone 3 acetylation (H3Ac) and histone 4 acetylation (H4Ac) levels were measured in six immune genes previously associated with helminth immunity by chromatin immunoprecipitation (ChIP)-quantitative PCR.,Then we analyzed the association between histone acetylation levels with total parasite egg burden and IgE levels.,We found an inverse correlation between H4Ac levels in the IL13 gene and egg worm burden that remained significant after adjustment by age [−0.20 (−0.32 to −0.09), p < 0.0001].,Moreover, we found significant associations between H4Ac levels in IL4 [0.32 (0.05-0.60), p = 0.02] and CHI3L1 [0.29 (0.08-0.51), p = 0.008] with the IgE levels to Ascaris lumbricoides.,In addition, the levels of specific IgE antibodies to HDM were associated with H4Ac levels in the gene TNFSF13B encoding the B cell activating factor (BAFF) [0.51 (0.26-0.76), p < 0.001].,All values are presented as beta (95% CI).,Histone acetylation levels at key type-2 immune genes in humans were modified by nematode infection and HDM allergens and are associated with the intensity of the IgE response.

Intestinal parasitic nematodes live in intimate contact with the host microbiota.,Changes in the microbiome composition during nematode infection affect immune control of the parasites and shifts in the abundance of bacterial groups have been linked to the immunoregulatory potential of nematodes.,Here we asked if the small intestinal parasite Heligmosomoides polygyrus produces factors with antimicrobial activity, senses its microbial environment and if the anti-nematode immune and regulatory responses are altered in mice devoid of gut microbes.,We found that H. polygyrus excretory/secretory products exhibited antimicrobial activity against gram+/− bacteria.,Parasites from germ-free mice displayed alterations in gene expression, comprising factors with putative antimicrobial functions such as chitinase and lysozyme.,Infected germ-free mice developed increased small intestinal Th2 responses coinciding with a reduction in local Foxp3+RORγt+ regulatory T cells and decreased parasite fecundity.,Our data suggest that nematodes sense their microbial surrounding and have evolved factors that limit the outgrowth of certain microbes.,Moreover, the parasites benefit from microbiota-driven immune regulatory circuits, as an increased ratio of intestinal Th2 effector to regulatory T cells coincides with reduced parasite fitness in germ-free mice.

...,Even though eliminating malaria from the endemic margins is a part of the Global Malaria Action Plan, little guidance exists on what resources are needed to transition from controlling malaria to eliminating it.,Using Philippines as an example, this study aimed to (1) estimate the financial resources used by sub-national malaria programs in different phases during elimination and (2) understand how different environmental and organizational factors may influence expenditure levels and spending proportions.,The Philippines provides an opportunity to study variations in sub-national programs because its epidemiological and ecological diversity, devolved health system, and progressive elimination strategy all allow greater flexibility for lower-level governments to direct activities, but also create challenges for coordination and resource mobilization.,Through key informant interviews and archival record retrieval in four selected provinces chosen based on eco-epidemiological variation, expenditures associated with provincial malaria programs were collected for selected years (mid-1990s to 2010).,Results show that expenditures per person at risk per year decrease as programs progress from a state of controlled low-endemic malaria to elimination to prevention of reintroduction regardless of whether elimination was deliberately planned.,However, wide variation across provinces were found: expenditures were generally higher if mainly financed with donor grants, but were moderated by the level of economic development, the level of malaria transmission and receptivity, and the capacity of program staff.,Across all provinces, strong leadership appears to be a necessary condition for maintaining progress and is vital in controlling outbreaks.,While sampled provinces and years may not be representative of other sub-national malaria programs, these findings suggest that the marginal yearly cost declines with each phase during elimination.

As countries move towards malaria elimination, methods to identify infections among populations who do not seek treatment are required.,Reactive case detection, whereby individuals living in close proximity to passively detected cases are screened and treated, is one approach being used by a number of countries including Swaziland.,An outstanding issue is establishing the epidemiologically and operationally optimal screening radius around each passively detected index case.,Using data collected between December 2009 and June 2012 from reactive case detection (RACD) activities in Swaziland, we evaluated the effect of screening radius and other risk factors on the probability of detecting cases by reactive case detection.,Using satellite imagery, we also evaluated the household coverage achieved during reactive case detection.,Over the study period, 250 cases triggered RACD, which identified a further 74 cases, showing the value of RACD over passive surveillance alone.,Results suggest that the odds of detecting a case within the household of the index case were significantly higher than in neighbouring households (odds ratio (OR) 13, 95% CI 3.1-54.4).,Furthermore, cases were more likely to be detected when RACD was conducted within a week of the index presenting at a health facility (OR 8.7, 95% CI 1.1-66.4) and if the index household had not been sprayed with insecticide (OR sprayed vs not sprayed 0.11, 95% CI 0.03-0.46).,The large number of households missed during RACD indicates that a 1 km screening radius may be impractical in such resource limited settings such as Swaziland.,Future RACD in Swaziland could be made more effective by achieving high coverage amongst individuals located near to index cases and in areas where spraying has not been conducted.,As well as allowing the programme to implement RACD more rapidly, this would help to more precisely define the optimal screening radius.

Behavioral resilience in mosquitoes poses a significant challenge to mosquito control.,Although behavior changes in anopheline vectors have been reported over the last decade, there are no empirical data to suggest they compromise the efficacy of vector control in reducing malaria transmission.,In this study, we quantified human exposure to both bites and infective bites of a major malaria vector in Papua New Guinea over the course of 4 years surrounding nationwide bednet distribution.,We also quantified malaria infection prevalence in the human population during the same time period.,We observed a shift in mosquito biting to earlier hours of the evening, before individuals are indoors and protected by bednets, followed by a return to preintervention biting rates.,As a result, net users and non-net users experienced higher levels of transmission than before the intervention.,The personal protection provided by a bednet decreased over the study period and was lowest in the adult population, who may be an important reservoir for transmission.,Malaria prevalence decreased in only 1 of 3 study villages after the distribution.,This study highlights the necessity of validating and deploying vector control measures targeting outdoor exposure to control and eliminate malaria.

The Amazon environment has been exposed in the last decades to radical changes that have been accompanied by a remarkable rise of both Plasmodium falciparum and Plasmodium vivax malaria.,The malaria transmission process is highly influenced by factors such as spatial and temporal heterogeneities of the environment and individual-based characteristics of mosquitoes and humans populations.,All these determinant factors can be simulated effectively trough agent-based models.,This paper presents a validated agent-based model of local-scale malaria transmission.,The model reproduces the environment of a typical riverine village in the northern Peruvian Amazon, where the malaria transmission is highly seasonal and apparently associated with flooding of large areas caused by the neighbouring river.,Agents representing humans, mosquitoes and the two species of Plasmodium (P.falciparum and P. vivax) are simulated in a spatially explicit representation of the environment around the village.,The model environment includes: climate, people houses positions and elevation.,A representation of changes in the mosquito breeding areas extension caused by the river flooding is also included in the simulation environment.,A calibration process was carried out to reproduce the variations of the malaria monthly incidence over a period of 3 years.,The calibrated model is also able to reproduce the spatial heterogeneities of local scale malaria transmission.,A “what if” eradication strategy scenario is proposed: if the mosquito breeding sites are eliminated through mosquito larva habitat management in a buffer area extended at least 200 m around the village, the malaria transmission is eradicated from the village.,The use of agent-based models can reproduce effectively the spatiotemporal variations of the malaria transmission in a low endemicity environment dominated by river floodings like in the Amazon.

In the Greater Mekong Subregion in Southeast Asia, malaria elimination strategies need to target all Plasmodium falciparum parasites, including those carried asymptomatically.,More than 70% of asymptomatic carriers are not detected by current rapid diagnostic tests (RDTs) or microscopy.,In the Greater Mekong Subregion in Southeast Asia, malaria elimination strategies need to target all Plasmodium falciparum parasites, including those carried asymptomatically.,More than 70% of asymptomatic carriers are not detected by current rapid diagnostic tests (RDTs) or microscopy.,An HRP2-based ultrasensitive RDT (uRDT) developed to improve the detection of low-density infections was evaluated during prevalence surveys within a malaria elimination program in a low-transmission area of eastern Myanmar.,Surveys were conducted to identify high-prevalence villages.,Two-milliliter venous blood samples were collected from asymptomatic adult volunteers and transported to the laboratory.,Plasmodium parasites were detected by RDT, uRDT, microscopy, ultrasensitive qPCR (uPCR), and multiplex enzyme-linked immunosorbent assay (ELISA).,The sensitivity, specificity, and predictive positive and negative values of RDT and uRDT were calculated compared to uPCR and ELISA.,Parasite and antigen concentrations detected by each test were defined using uPCR and ELISA, respectively.,A total of 1,509 samples, including 208 P. falciparum-positive samples were analyzed with all tests.,The sensitivity of the uRDT was twofold higher than that of RDT, 51.4% versus 25.2%, with minor specificity loss, 99.5% versus 99.9%, against the combined reference (uPCR plus ELISA).,The geometric mean parasitemia detected by uRDT in P. falciparum monospecific infections was 3,019 parasites per ml (95% confidence interval [95% CI], 1,790 to 5,094; n = 79) compared to 11,352 parasites per ml (95% CI, 5,643 to 22,837; n = 38) by RDT.,The sensitivities of uRDT and RDT dropped to 34.6% and 15.1%, respectively, for the matched tests performed in the field.,The uRDT performed consistently better than RDT and microscopy at low parasitemias.,It shows promising characteristics for the identification of high-prevalence communities and warrants further evaluation in mass screening and treatment interventions.

Sri Lanka has made remarkable gains in reducing the burden of malaria, recording no locally transmitted malaria cases since November 2012 and zero deaths since 2007.,The country was recently certified as malaria free by World Health Organization in September 2016.,Sri Lanka, however, continues to face a risk of resurgence due to persistent receptivity and vulnerability to malaria transmission.,Maintaining the gains will require continued financing to the malaria program to maintain the activities aimed at preventing reintroduction.,This article presents an investment case for malaria in Sri Lanka by estimating the costs and benefits of sustaining investments to prevent the reintroduction of the disease.,An ingredient-based approach was used to estimate the cost of the existing program.,The cost of potential resurgence was estimated using a hypothetical scenario in which resurgence assumed to occur, if all prevention of reintroduction activities were halted.,These estimates were used to compute a benefit-cost ratio and a return on investment.,The total economic cost of the malaria program in 2014 was estimated at U.S. dollars (USD) 0.57 per capita per year with a financial cost of USD0.37 per capita.,The cost of potential malaria resurgence was, however, much higher estimated at 13 times the cost of maintaining existing activities or 21 times based on financial costs alone.,This evidence suggests a substantial return on investment providing a compelling argument for advocacy for continued prioritization of funding for the prevention of reintroduction of malaria in Sri Lanka.

Early diagnosis and treatment is the principal strategy to control visceral leishmaniasis (VL), or kala-azar in East Africa.,As VL strikes remote rural, sparsely populated areas, kala-azar care might not be accessed optimally or timely.,We conducted a qualitative study to explore access barriers in a longstanding kala-azar endemic area in southern Gadarif, Sudan.,Former kala-azar patients or caretakers, community leaders, and health-care providers were purposively sampled and thematic data analysis was used.,Our study participants revealed the multitude of difficulties faced when seeking care.,The disease is well known in the area, yet misconceptions about causes and transmission persist.,The care-seeking itineraries were not always straightforward: “shopping around” for treatments are common, partly linked to difficulties in diagnosing kala-azar.,Kala-azar is perceived to be “hiding,” requiring multiple tests and other diseases must be treated first.,Negative perceptions on quality of care in the public hospitals prevail, with the unavailability of drugs or staff as the main concern.,Delay to seek care remains predominantly linked to economic constraint: albeit treatment is for free, patients have to pay out of pocket for everything else, pushing families further into poverty.,Despite increased efforts to tackle the disease over the years, access to quality kala-azar care in this rural Sudanese context remains problematic.,The barriers explored in this study are a compelling reminder of the need to boost efforts to address these barriers.

Visceral leishmaniasis (VL) is a neglected parasitic disease that is fatal if left untreated and is endemic in eastern Sudan.,We estimated the direct and indirect costs of treatment of VL from the perspective of the provider and the household at three public hospitals in Gedaref State.,The median total cost for one VL episode was estimated to be US$450.,Despite the free provision of VL drugs at public hospitals, households bore 53% of the total cost of VL with one episode of VL representing 40% of the annual household income.,More than 75% of households incurred catastrophic out-of-pocket expenditures.,The length of treatment of 30 days led to important costs for both health providers and households.,Alternative treatment regimens that reduce the duration of treatment are urgently needed.

Morbidity management and disability prevention (MMDP) services are essential for the management of chronic stages of lymphatic filariasis (LF) infection.,However, there is limited information on health beliefs and health seeking behavior towards MMDP services for LF in endemic regions of Zambia.,This study sought to document health beliefs and health seeking behavior towards MMDP services for LF in Luangwa District, Zambia.,This was an exploratory qualitative study conducted with community members including LF patients, community health workers and healthcare providers.,Data was collected through a series of four focus group discussions stratified by sex and 26 in-depth interviews.,Data was analyzed by thematic analysis using NVivo software.,The perceived causes of the chronic manifestations of LF included; contact with animal faeces, use of traditional herbal aphrodisiacs (mutoto), witchcraft and sexual contact with women who were menstruating or had miscarried.,LF patients opted to visit traditional healers before going to health facilities.,Hydrocele patients were afraid of hydrocelectomies as they were thought to cause infertility or death.,Very few community members were able to identify any home and facility-based care strategies for lymphoedema.,Health system and cultural barriers to seeking healthcare included; long distances to the health facilities, lack of awareness of existing MMDP services, perceived costs of accessing MMDP services, gender and social norms, and fear of stigmatization.,Health seeking behavior for LF in the district is mainly driven by negative beliefs about the causes of the disease and lack of awareness of available MMDP services and homecare strategies.,Lymphatic filariasis programs should promote strategies that seek to empower patients and community members with the required information to access and use the MMDP services at the health facilities, as well as adhere to self-care practices in their households.

Podoconiosis, lymphatic filariasis (LF) and leprosy are neglected tropical diseases (NTDs) that cause lymphoedema.,When left untreated, they lead to substantial disability.,This study determined the quality of life (QOL) and depression associated with lymphoedema in patients with podoconiosis, LF and leprosy.,The study was conducted in northwestern Ethiopia.,This baseline cross-sectional study, nested within an interventional, non-comparative, longitudinal study, included patients with lymphoedema.,Depression and QOL were assessed using versions of the 9-item Patient Health Questionnaire and Dermatologic Life Quality Index (DLQI), respectively, that had been translated into Amharic and validated.,Factors associated with depression and QOL were assessed using multivariate linear regression analysis.,Of the 251 patients with lymphoedema included in the study, 119 (47.4%) had moderate to severe depression and overall QOL was poor (mean±standard deviation [SD] DLQI score: 11.4±4.2).,Disability was significantly associated with depression (β=0.26 [95% confidence interval {CI} 0.19 to 0.33]).,Currently receiving treatment (β=−3.05 [95% CI −5.25 to −0.85), disability (β=−0.08 [95% CI −0.15 to −0.01]) and social support (moderate support: β=−2.27 [95% CI −3.66 to −0.89] and strong support: β=−2.87 [95% CI −5.35 to −0.38]) were significantly associated with better QOL.,High levels of depression and low QOL were found among patients with lymphoedema due the three NTDs in Ethiopia.

Our group has recently provided a proof-of-principle for the examination of pooled stool samples using McMaster technique as a strategy for the rapid assessment of intensity of soil-transmitted helminth infections (STH, Ascaris lumbricoides, Trichuris trichiura and hookworm).,In the present study we evaluated this pooling strategy for the assessment of intensity of both STH and Schistosoma mansoni infections using the Kato-Katz technique.,A cross-sectional survey was conducted in 360 children aged 5-18 years from six schools in Jimma Zone (southwest Ethiopia).,We performed faecal egg counts (FECs) in both individual and pooled samples (pools sizes of 5, 10 and 20) to estimate the number of eggs per gram of stool (EPG) using the Kato-Katz technique.,We also assessed the time to screen both individual and pooled samples.,Except for hookworms, there was a significant correlation (correlation coefficient = 0.53-0.95) between the mean of individual FECs and the FECs of pooled samples for A. lumbricoides, T. trichiura and S. mansoni, regardless of the pool size.,Mean FEC were 2,596 EPG, 125 EPG, 47 EPG, and 41 EPG for A. lumbricoides, T. trichiura, S. mansoni and hookworm, respectively.,There was no significant difference in FECs between the examination of individual and pooled stool samples, except for hookworms.,For this STH, pools of 10 resulted in a significant underestimation of infection intensity.,The total time to obtain individual FECs was 65 h 5 min.,For pooled FECs, this was 19 h 12 min for pools of 5, 14 h 39 min for pools of 10 and 12 h 42 min for pools of 20.,The results indicate that pooling of stool sample holds also promise as a rapid assessment of infections intensity for STH and S. mansoni using the Kato-Katz technique.,In this setting, the time in the laboratory was reduced by 70 % when pools of 5 instead of individual stool samples were screened.

•A Bayesian latent class meta-analysis of diagnostic tests for soil-transmitted helminths was performed.,•Overall sensitivity of evaluated diagnostic tests was low.,•Test performance was strongly influenced by intensity of infection.,•FLOTAC method sensitivity was highest overall and in both intensity groups.,•The performance of the Kato-Katz method in high intensity settings was acceptable.,A Bayesian latent class meta-analysis of diagnostic tests for soil-transmitted helminths was performed.,Overall sensitivity of evaluated diagnostic tests was low.,Test performance was strongly influenced by intensity of infection.,FLOTAC method sensitivity was highest overall and in both intensity groups.,The performance of the Kato-Katz method in high intensity settings was acceptable.,Reliable, sensitive and practical diagnostic tests are an essential tool in disease control programmes for mapping, impact evaluation and surveillance.,To provide a robust global assessment of the relative performance of available diagnostic tools for the detection of soil-transmitted helminths, we conducted a meta-analysis comparing the sensitivities and the quantitative performance of the most commonly used copro-microscopic diagnostic methods for soil-transmitted helminths, namely Kato-Katz, direct microscopy, formol-ether concentration, McMaster, FLOTAC and Mini-FLOTAC.,In the absence of a perfect reference standard, we employed a Bayesian latent class analysis to estimate the true, unobserved sensitivity of compared diagnostic tests for each of the soil-transmitted helminth species Ascaris lumbricoides, Trichuris trichiura and the hookworms.,To investigate the influence of varying transmission settings we subsequently stratified the analysis by intensity of infection.,Overall, sensitivity estimates varied between the different methods, ranging from 42.8% for direct microscopy to 92.7% for FLOTAC.,The widely used double slide Kato-Katz method had a sensitivity of 74-95% for the three soil-transmitted helminth species at high infection intensity, however sensitivity dropped to 53-80% in low intensity settings, being lowest for hookworm and A. lumbricoides.,The highest sensitivity, overall and in both intensity groups, was observed for the FLOTAC method, whereas the sensitivity of the Mini-FLOTAC method was comparable with the Kato-Katz method.,FLOTAC average egg count estimates were significantly lower compared with Kato-Katz, while the compared McMaster counts varied.,In conclusion, we demonstrate that the Kato-Katz and Mini-FLOTAC methods had comparable sensitivities.,We further show that test sensitivity of the Kato-Katz method is reduced in low transmission settings.

Infection with the helminth Schistosoma (S.) mansoni drives the development of interleukin (IL)-10-producing regulatory B (Breg) cells in mice and man, which have the capacity to reduce experimental allergic airway inflammation and are thus of high therapeutic interest.,However, both the involved antigen and cellular mechanisms that drive Breg cell development remain to be elucidated.,Therefore, we investigated whether S. mansoni soluble egg antigens (SEA) directly interact with B cells to enhance their regulatory potential, or act indirectly on B cells via SEA-modulated macrophage subsets.,Intraperitoneal injections of S. mansoni eggs or SEA significantly upregulated IL-10 and CD86 expression by marginal zone B cells.,Both B cells as well as macrophages of the splenic marginal zone efficiently bound SEA in vivo, but macrophages were dispensable for Breg cell induction as shown by macrophage depletion with clodronate liposomes.,SEA was internalized into acidic cell compartments of B cells and induced a 3-fold increase of IL-10, which was dependent on endosomal acidification and was further enhanced by CD40 ligation.,IPSE/alpha-1, one of the major antigens in SEA, was also capable of inducing IL-10 in naïve B cells, which was reproduced by tobacco plant-derived recombinant IPSE.,Other major schistosomal antigens, omega-1 and kappa-5, had no effect.,SEA depleted of IPSE/alpha-1 was still able to induce Breg cells indicating that SEA contains more Breg cell-inducing components.,Importantly, SEA- and IPSE-induced Breg cells triggered regulatory T cell development in vitro.,SEA and recombinant IPSE/alpha-1 also induced IL-10 production in human CD1d+ B cells.,In conclusion, the mechanism of S. mansoni-induced Breg cell development involves a direct targeting of B cells by SEA components such as the secretory glycoprotein IPSE/alpha-1.

The trematode Fasciola hepatica is responsible for chronic zoonotic infection globally.,Despite causing a potent T-helper 2 response, it is believed that potent immunomodulation is responsible for rendering this host reactive non-protective host response thereby allowing the parasite to remain long-lived.,We have previously identified a growth factor, FhTLM, belonging to the TGF superfamily can have developmental effects on the parasite.,Herein we demonstrate that FhTLM can exert influence over host immune functions in a host receptor specific fashion.,FhTLM can bind to receptor members of the Transforming Growth Factor (TGF) superfamily, with a greater affinity for TGF-β RII.,Upon ligation FhTLM initiates the Smad2/3 pathway resulting in phenotypic changes in both fibroblasts and macrophages.,The formation of fibroblast CFUs is reduced when cells are cultured with FhTLM, as a result of TGF-β RI kinase activity.,In parallel the wound closure response of fibroblasts is also delayed in the presence of FhTLM.,When stimulated with FhTLM blood monocyte derived macrophages adopt an alternative or regulatory phenotype.,They express high levels interleukin (IL)-10 and arginase-1 while displaying low levels of IL-12 and nitric oxide.,Moreover they also undergo significant upregulation of the inhibitory receptor PD-L1 and the mannose receptor.,Use of RNAi demonstrates that this effect is dependent on TGF-β RII and mRNA knock-down leads to a loss of IL-10 and PD-L1.,Finally, we demonstrate that FhTLM aids newly excysted juveniles (NEJs) in their evasion of antibody-dependent cell cytotoxicity (ADCC) by reducing the NO response of macrophages-again dependent on TGF-β RI kinase.,FhTLM displays restricted expression to the F. hepatica gut resident NEJ stages.,The altered fibroblast responses would suggest a role for dampened tissue repair responses in facilitating parasite migration.,Furthermore, the adoption of a regulatory macrophage phenotype would allow for a reduced effector response targeting juvenile parasites which we demonstrate extends to an abrogation of the ADCC response.,Thus suggesting that FhTLM is a stage specific evasion molecule that utilises host cytokine receptors.,These findings are the first to clearly demonstrate the interaction of a helminth cytokine with a host receptor complex resulting in immune modifications that facilitate the non-protective chronic immune response which is characteristic of F. hepatica infection.

The island of Hispaniola, shared by Haiti and the Dominican Republic (DR), is the only remaining malaria-endemic island in the Caribbean and accounts for 95% of the lymphatic filariasis (LF) burden in the Americas.,Both countries aim to eliminate the diseases by 2020.,Migration from Haiti, where both diseases are more prevalent, may promote transmission in the DR.,Historically, Haitian migrant labourers live in rural Dominican agricultural ‘company towns’ called bateyes, many of which received mass drug administration (MDA) for LF elimination.,This study sought to determine the prevalence of malaria and LF in bateyes of the DR and to describe related risk factors for disease.,From March to April 2016, a cross-sectional, cluster survey was conducted across Dominican bateyes stratified into three regions: southwest, north and east.,A household questionnaire (n = 776), captured demographics, ethnic origin, mobility patterns, malaria intervention coverage, and knowledge, and recent fever and treatment-seeking.,Two individuals per household (n = 1418) were tested for malaria parasites by microscopy and rapid diagnostic test (RDT) and LF antigen by filariasis test strip (FTS).,Population-level estimates and confidence intervals (CI) were computed adjusting for the survey design.,Two-sided t-tests compared differences in knowledge scores.,No (0%) blood sample was Plasmodium-positive by microscopy or RDT.,Six individuals were FTS-positive (0.5%; 95% CI: 0.2-1.5), but none (0%) of these were microfilariae-positive.,Most batey residents were born in the DR (57.8%), documented (85.0%), and permanent residents (85.1%).,Very few respondents (9.4%) reported travel to Haiti in the past year.,Overall, half (53.8%) of respondents owned a bed net, and 82.3% of net owners reported using it the previous night.,Indoor residual spraying (IRS) differed by region (range: 4.7%-61.2%).,Most of those with recent fever sought care (56.0%), yet only 30.5% of those seeking care were tested for malaria.,Compared to Dominican-born populations, Haitian-born respondents more frequently reported recent fever, did not seek care for the fever, had not heard of malaria, and could not name symptoms or prevention methods.,Malaria and LF transmission appear absent or extremely low in Dominican bateyes, which are a mixture of Haitian and Dominican residents.,Travel to Haiti is rare, meaning risk of malaria and LF importation is low.,Addressing identified gaps in intervention coverage, malaria knowledge, treatment seeking and service delivery will improve the quality of surveillance for these diseases, particularly among marginalized populations and promote island-wide elimination.,The online version of this article (10.1186/s40249-019-0547-3) contains supplementary material, which is available to authorized users.

Lymphatic filariasis (LF) and soil-transmitted helminths (STH) have been targeted since 2000 in Haiti, with a strong mass drug administration (MDA) program led by the Ministry of Public Health and Population and its collaborating international partners.,By 2012, Haiti’s neglected tropical disease (NTD) program had reached full national scale, and with such consistently good epidemiological coverage that it is now able to stop treatment for LF throughout almost all of the country.,Essential to this success have been in the detail of how MDAs were implemented.,These key programmatic elements included ensuring strong community awareness through an evidence-based, multi-channel communication and education campaign facilitated by voluntary drug distributors; strengthening community trust of the drug distributors by ensuring that respected community members were recruited and received appropriate training, supervision, identification, and motivation; enforcing a “directly observed treatment” strategy; providing easy access to treatment though numerous distribution posts and a strong drug supply chain; and ensuring quality data collection that was used to guide and inform MDA strategies.,The evidence that these strategies were effective lies in both the high treatment coverage obtained- 100% geographical coverage reached in 2012, with almost all districts consistently achieving well above the epidemiological coverage targets of 65% for LF and 75% for STH-and the significant reduction in burden of infection- 45 communes having reached the target threshold for stopping treatment for LF.,By taking advantage of sustained international financial and technical support, especially during the past eight years, Haiti’s very successful MDA campaign resulted in steady progress toward LF elimination and development of a strong foundation for ongoing STH control.,These efforts, as described, have not only helped establish the global portfolio of “best practices” for NTD control but also are poised to help solve two of the most important future NTD challenges-how to maintain control of STH infections after the community-based LF “treatment platform” ceases and how to ensure appropriate morbidity management for patients currently suffering from lymphatic filarial disease.

Improvements to housing may contribute to malaria control and elimination by reducing house entry by malaria vectors and thus exposure to biting.,We tested the hypothesis that the odds of malaria infection are lower in modern, improved housing compared to traditional housing in sub-Saharan Africa (SSA).,We analysed 15 Demographic and Health Surveys (DHS) and 14 Malaria Indicator Surveys (MIS) conducted in 21 countries in SSA between 2008 and 2015 that measured malaria infection by microscopy or rapid diagnostic test (RDT).,DHS/MIS surveys record whether houses are built with finished materials (e.g., metal) or rudimentary materials (e.g., thatch).,This information was used to develop a binary housing quality variable where houses built using finished wall, roof, and floor materials were classified as “modern”, and all other houses were classified as “traditional”.,Conditional logistic regression was used to determine the association between housing quality and prevalence of malaria infection in children aged 0-5 y, adjusting for age, gender, insecticide-treated net (ITN) use, indoor residual spraying, household wealth, and geographic cluster.,Individual survey odds ratios (ORs) were combined to determine a summary OR using a random effects meta-analysis.,Of 284,532 total children surveyed, 139,318 were tested for malaria infection using microscopy (n = 131,652) or RDT (n = 138,540).,Within individual surveys, malaria prevalence measured by microscopy ranged from 0.4% (Madagascar 2011) to 45.5% (Burkina Faso 2010) among children living in modern houses and from 0.4% (The Gambia 2013) to 70.6% (Burkina Faso 2010) in traditional houses, and malaria prevalence measured by RDT ranged from 0.3% (Senegal 2013-2014) to 61.2% (Burkina Faso 2010) in modern houses and from 1.5% (The Gambia 2013) to 79.8% (Burkina Faso 2010) in traditional houses.,Across all surveys, modern housing was associated with a 9% to 14% reduction in the odds of malaria infection (microscopy: adjusted OR 0.91, 95% CI 0.85-0.97, p = 0.003; RDT: adjusted OR 0.86, 95% CI 0.80-0.92, p < 0.001).,This association was consistent regardless of ITN usage.,As a comparison, the odds of malaria infection were 15% to 16% lower among ITN users versus non-users (microscopy: adjusted OR 0.84, 95% CI 0.79-0.90, p < 0.001; RDT: adjusted OR 0.85, 95% CI 0.80-0.90, p < 0.001).,The main limitation of this study is that residual confounding by household wealth of the observed association between housing quality and malaria prevalence is possible, since the wealth index may not have fully captured differences in socioeconomic position; however, the use of multiple national surveys offers the advantage of a large sample size and the elimination of many biases typically associated with pooling observational data.,Housing quality is an important risk factor for malaria infection across the spectrum of malaria endemicity in SSA, with a strength of association between housing quality and malaria similar to that observed between ITN use and malaria.,Improved housing should be considered a promising intervention for malaria control and elimination and long-term prevention of reintroduction.,Lucy Tusting and colleagues investigate the association between housing quality and malaria infection in children under 5 living in sub-Saharan Africa.

As malaria transmission declines, it becomes more geographically focused and more likely due to asymptomatic and non-falciparum infections.,To inform malaria elimination planning in the context of this changing epidemiology, local assessments on the risk factors for malaria infection are necessary, yet challenging due to the low number of malaria cases.,A population-based, cross-sectional study was performed using passive and active surveillance data collected in Aceh Besar District, Indonesia from 2014 to 2015.,Malaria infection was defined as symptomatic polymerase chain reaction (PCR)-confirmed infection in index cases reported from health facilities, and asymptomatic or symptomatic PCR-confirmed infection identified in reactive case detection (RACD).,Potential risk factors for any infection, species-specific infection, or secondary-case detection in RACD were assessed through questionnaires and evaluated for associations.,Nineteen Plasmodium knowlesi, 12 Plasmodium vivax and six Plasmodium falciparum cases were identified passively, and 1495 community members screened in RACD, of which six secondary cases were detected (one P. knowlesi, three P. vivax, and two P. falciparum, with four being asymptomatic).,Compared to non-infected subjects screened in RACD, cases identified through passive or active surveillance were more likely to be male (AOR 12.5, 95 % CI 3.0-52.1), adult (AOR 14.0, 95 % CI 2.2-89.6 for age 16-45 years compared to <15 years), have visited the forest in the previous month for any reason (AOR 5.6, 95 % CI 1.3-24.2), and have a workplace near or in the forest and requiring overnight stays (AOR 7.9, 95 % CI 1.6-39.7 compared to workplace not near or in the forest).,Comparing subjects with infections of different species, differences were observed in sub-district of residence and other demographic and behavioural factors.,Among subjects screened in RACD, cases compared to non-cases were more likely to be febrile and reside within 100 m of the index case.,In this setting, risk of malaria infection in index and RACD identified cases was associated with forest exposure, particularly overnights in the forest for work.,In low-transmission settings, utilization of data available through routine passive and active surveillance can support efforts to target individuals at high risk.

Due to outdoor and residual transmission and insecticide resistance, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) will be insufficient as stand-alone malaria vector control interventions in many settings as programmes shift toward malaria elimination.,Combining additional vector control interventions as part of an integrated strategy would potentially overcome these challenges.,Larval source management (LSM) and structural house improvements (HI) are appealing as additional components of an integrated vector management plan because of their long histories of use, evidence on effectiveness in appropriate settings, and unique modes of action compared to LLINs and IRS.,Implementation of LSM and HI through a community-based approach could provide a path for rolling-out these interventions sustainably and on a large scale.,We will implement community-based LSM and HI, as additional interventions to the current national malaria control strategies, using a randomised block, 2 × 2 factorial, cluster-randomised design in rural, southern Malawi.,These interventions will be continued for two years.,The trial catchment area covers about 25,000 people living in 65 villages.,Community participation is encouraged by training community volunteers as health animators, and supporting the organisation of village-level committees in collaboration with The Hunger Project, a non-governmental organisation.,Household-level cross-sectional surveys, including parasitological and entomological sampling, will be conducted on a rolling, 2-monthly schedule to measure outcomes over two years (2016 to 2018).,Coverage of LSM and HI will also be assessed throughout the trial area.,Combining LSM and/or HI together with the interventions currently implemented by the Malawi National Malaria Control Programme is anticipated to reduce malaria transmission below the level reached by current interventions alone.,Implementation of LSM and HI through a community-based approach provides an opportunity for optimum adaptation to the local ecological and social setting, and enhances the potential for sustainability.,Registered with The Pan African Clinical Trials Registry on 3 March 2016, trial number PACTR201604001501493.,The online version of this article (10.1186/s12879-017-2749-2) contains supplementary material, which is available to authorized users.

Background Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are highly effective tools for controlling malaria transmission in Africa because the most important vectors, from the Anopheles gambiae complex and the A. funestus group, usually prefer biting humans indoors at night.,Methods Matched surveys of mosquito and human behaviour from six rural sites in Burkina Faso, Tanzania, Zambia, and Kenya, with ITN use ranging from 0.2% to 82.5%, were used to calculate the proportion of human exposure to An. gambiae sensu lato and An. funestus s.l. that occurs indoors (πi), as an indicator of the upper limit of personal protection that indoor vector control measures can provide.,This quantity was also estimated through use of a simplified binary analysis (πiB) so that the proportions of mosquitoes caught indoors (Pi), and between the first and last hours at which most people are indoors (Pfl) could also be calculated as underlying indicators of feeding by mosquitoes indoors or at night, respectively.,Results The vast majority of human exposure to Anopheles bites occurred indoors (πiB = 0.79-1.00).,Neither An. gambiae s.l. nor An. funestus s.l. strongly preferred feeding indoors (Pi = 0.40-0.63 and 0.22-0.69, respectively), but they overwhelmingly preferred feeding at times when most humans were indoors (Pfl = 0.78-1.00 and 0.86-1.00, respectively).,Conclusions These quantitative summaries of behavioural interactions between humans and mosquitoes constitute a remarkably consistent benchmark with which future observations of vector behaviour can be compared.,Longitudinal monitoring of these quantities is vital to evaluate the effectiveness of ITNs and IRS and the need for complementary measures that target vectors outdoors.

Malaria transmission is influenced by climate, land use and deliberate intervention.,Recent declines have been observed in malaria transmission.,Here, we show that the continent has witnessed a long-term recession in the prevalence of Plasmodium falciparum since 1900-29 (40%) to 2010-15 (24%), interrupted at different times by periods of rapidly increasing and decreasing transmission.,The cycles and trend over the last 115 years are inconsistent with simplistic explanations in terms of climate or intervention alone.,Previous global initiatives had minor impacts on malaria transmission, and a historically unprecedented decline has been observed since 2000.,However, there has been little change to the continued high transmission belt covering large parts of West and Central Africa.,Previous efforts to model the changing patterns of P. falciparum transmission intensity in Africa have been limited to the last 15 years1,2, or have used maps of historical expert opinion3.,We provide quantitative data comprising 50,424 surveys at 36,966 geocoded locations to cover 115 years of malaria history in sub-Saharan Africa.

The recent emergence of artemisinin resistance in the Greater Mekong Subregion poses a major threat to the global effort to control malaria.,Tracking the spread and evolution of artemisinin-resistant parasites is critical in aiding efforts to contain the spread of resistance.,A total of 417 patient samples from the year 2007, collected during malaria surveillance studies across ten provinces in Thailand, were genotyped for the candidate Plasmodium falciparum molecular marker of artemisinin resistance K13.,Parasite genotypes were examined for K13 propeller mutations associated with artemisinin resistance, signatures of positive selection, and for evidence of whether artemisinin-resistant alleles arose independently across Thailand.,A total of seven K13 mutant alleles were found (N458Y, R539T, E556D, P574L, R575K, C580Y, S621F).,Notably, the R575K and S621F mutations have previously not been reported in Thailand.,The most prevalent artemisinin resistance-associated K13 mutation, C580Y, carried two distinct haplotype profiles that were separated based on geography, along the Thai-Cambodia and Thai-Myanmar borders.,It appears these two haplotypes may have independent evolutionary origins.,In summary, parasites with K13 propeller mutations associated with artemisinin resistance were widely present along the Thai-Cambodia and Thai-Myanmar borders prior to the implementation of the artemisinin resistance containment project in the region.

Anopheles stephensi mosquitoes are urban malaria vectors in Asia that have recently invaded the Horn of Africa.,We detected emergence of An. stephensi mosquitoes in 2 noncontiguous states of eastern Sudan.,Results of mitochondrial DNA sequencing suggest the possibility of distinct invasions, potentially from a neighboring country.

Adult traits of holometabolous insects are shaped by conditions experienced during larval development, which might impact interactions between adult insect hosts and parasites.,However, the ecology of larval insects that vector disease remains poorly understood.,Here, we used Anopheles stephensi mosquitoes and the human malaria parasite Plasmodium falciparum, to investigate whether larval conditions affect the capacity of adult mosquitoes to transmit malaria.,We reared larvae in two groups; one group received a standard laboratory rearing diet, whereas the other received a reduced diet.,Emerging adult females were then provided an infectious blood meal.,We assessed mosquito longevity, parasite development rate and prevalence of infectious mosquitoes over time.,Reduced larval food led to increased adult mortality and caused a delay in parasite development and a slowing in the rate at which parasites invaded the mosquito salivary glands, extending the time it took for mosquitoes to become infectious.,Together, these effects increased transmission potential of mosquitoes in the high food regime by 260-330%.,Such effects have not, to our knowledge, been shown previously for human malaria and highlight the importance of improving knowledge of larval ecology to better understand vector-borne disease transmission dynamics.

Soil-transmitted helminth infection (STH) is one of the neglected tropical disease that affects approximately 2 billion people globally.,School children represent the age group that is most commonly infected with STHs, resulting in poor school performance, impaired cognitive function, and many other detrimental effects.,The transmission of STH is determined by many factors, such as hygiene and sanitation.,Understanding the factors that influence disease transmission in a particular area is key to effective STH control.,The objective of this study was to determine the prevalence of STH in North Sumatera and to identify the associated risk factors among school children.,A cross-sectional study was carried out among primary school children in Suka village, Tigapanah subdistrict.,Stool samples were processed using a single Kato-Katz method.,The potential risk factors analyzed were parent education and occupation, hand washing habits, latrine usage, footwear usage and contact with soil.,The Chi-square test was performed to identify an association between risk factors and parasitological results.,Logistic regression analysis was used to measure the strength of association.,We enrolled 468 school children between 6 and 12 years of age.,Among those children, 268 children (57.24%) were positive for one or more STH infections.,Approximately 62.39% of children played with soil/dirt every day, and only 50% regularly washed their hands after activities.,Most of the children wore shoes/slippers when going outside (87.82%) and used a latrine for defecation (85.04%).,Playing with soil/dirt have been shown to increase the risk of STH infections 7.53 times, while hand washing habits and latrine usage decreased the risk of STH infections 0.16 times each.,The prevalence of STH infection in school children in Suka village, Tigapanah subdistrict is still high.,Playing with soil/dirt increased the risk of infection, while hand washing habits and latrine usage decreased the risk of infection.,The combined strategies of improving the personal hygiene of children and biannual deworming can reduce the risk of STH infection in school children in Suka village, Tigapanah subdistrict.,The online version of this article (10.1186/s12889-019-7397-6) contains supplementary material, which is available to authorized users.

Intestinal parasitic infections (IPIs) have been major public health problems in low income countries primarily affecting school children.,Previous studies in Ethiopia have shown high burden of intestinal parasitic infections in most children.,In order to gain a deeper insight into the magnitude of the problem more information is needed from different localities where similar studies have not been conducted.,The aim of this study was to assess the prevalence of IPIs and associated risk factors among school children in Jawi Primary School, Jawi town, north -west Ethiopia.,A cross-sectional study was conducted from April to June 2017 to assess the prevalence of IPIs and associated risk factors among Jawi Primary School children, Ethiopia.,A total of 422 children were selected using age-stratified systematic random sampling technique.,Stool samples were examined microscopically using direct wet-mount and formal-ether concentration techniques.,A structured questionnaire was used to obtain information regarding the associated risk factors.,Data were analyzed using SPSS version 20 and p value < 0.05 was taken as statistically significant.,Of 406 students examined for IPIs, 235 (57.88%) were positive for one or more intestinal parasites.,Single, double and triple infections were 41.9, 6.2 and 1.2%, respectively.,Overall infection rate was slightly higher in males (51.85%) than in females (45.30%) though the difference was not significant.,Higher prevalence rate (about 51-53%) was recorded among 6 to 18 years old children.,Prevalence of Giardia lamblia was the highest (19.95%), followed by hookworm (13.8%), Schistosoma mansoni (10.3%), Entamoeba histolytica/dispar (5.9%), Hymenolepsis nana (4.2%), Taenia species (3%) and Ascaris lumbricoides (0.73%), in that order.,Among the risk factors assessed, age, hand washing habit before meals, open field defecation habit, consistency of wearing shoes, habit of eating raw and unwashed vegetables, and finger nail cleanliness and trimming habit were found to be the most important predictors associated with high risk of IPIs (p < 0.05).,High prevalence of IPIs among Jawi Primary school children demands improved health education on regular hand washing, latrine use, wearing shoes, cleaning finger nails, not crossing rivers with bare foot and avoiding eating raw vegetables.,The online version of this article (10.1186/s12879-019-3971-x) contains supplementary material, which is available to authorized users.

Bacillus thuringiensis is a gram-positive soil-dwelling bacterium that is commonly used as a biological pesticide.,This bacterium may also be used for biological control of helminth parasites in domestic animals.,In this study, we evaluated the possible ovicidal and cestocidal effects of a total protein extract of B. thuringiensis native strains on the zoonotic cestode parasite of dogs, Dipylidium caninum (D. caninum).,Dose and time response curves were determined by coincubating B. thuringiensis proteins at concentration ranging from 100 to 1000 μg/mL along with 4000 egg capsules of D. caninum.,Egg viability was evaluated using the trypan blue exclusion test.,The lethal concentration of toxins on eggs was 600 μg/ml, and the best incubation time to produce this effect was 3 h.,In the adult stage, the motility and the thickness of the tegument were used as indicators of damage.,The motility was inhibited by 100% after 8 hours of culture compared to the control group, while the thickness of the cestode was reduced by 34%.,Conclusively, proteins of the strain GP526 of B. thuringiensis directly act upon D. caninum showing ovicidal and cestocidal effects.,Thus, B. thuringiensis is proposed as a potential biological control agent against this zoonosis.

Human clonorchiasis has been increasingly prevalent in recent years and results in a threat to the public health in epidemic regions, motivating current strategies of vaccines to combat Clonorchis sinensis (C. sinensis).,In this study, we identified C. sinensis paramyosin (CsPmy) from the cyst wall proteins of metacercariae by proteomic approaches and characterized the expressed recombinant pET-26b-CsPmy protein (101 kDa).,Bioinformatics analysis indicated that full-length sequences of paramyosin are conserved in helminthes and numerous B-cell/T-cell epitopes were predicted in amino acid sequence of CsPmy.,Western blot analysis showed that CsPmy was expressed at four life stages of C. sinensis, both cyst wall proteins and soluble tegumental components could be probed by anti-CsPmy serum.,Moreover, immunolocalization results revealed that CsPmy was specifically localized at cyst wall and excretory bladder of metacercaria, as well as the tegument, oral sucker and vitellarium of adult worm.,Both immunoblot and immunolocalization results demonstrated that CsPmy was highly expressed at the stage of adult worm, metacercariae and cercaria, which could be supported by real-time PCR analysis.,Both recombinant protein and nucleic acid of CsPmy showed strong immunogenicity in rats and induced combined Th1/Th2 immune responses, which were reflected by continuous high level of antibody titers and increased level of IgG1/IgG2a subtypes in serum.,In vaccine trials, comparing with control groups, both CsPmy protein and DNA vaccine exhibited protective effect with significant worm reduction rate of 54.3% (p<0.05) and 36.1% (p<0.05), respectively.,In consistence with immune responses in sera, elevated level of cytokines IFN-γ and IL-4 in splenocytes suggested that CsPmy could induce combined cellular immunity and humoral immunity in host.,Taken together, CsPmy could be a promising vaccine candidate in the prevention of C. sinensis regarding its high immunogenicity and surface localization.

DNA-based diagnostic methods have been shown to be highly sensitive and specific for the detection of malaria.,An 18S-rRNA-based, real-time polymerase chain reaction (PCR) was used to determine the prevalence and intensity of Plasmodium infections on Flores Island, Indonesia.,Microscopy and real-time multiplex PCR for the detection of Plasmodium species was performed on blood samples collected in a population-based study in Nangapanda Flores Island, Indonesia.,A total 1,509 blood samples were analysed.,Real-time PCR revealed prevalence for Plasmodium falciparum, Plasmodium vivax, and Plasmodium malariae to be 14.5%, 13.2%, and 1.9% respectively.,Sub-microscopic parasitaemia were found in more than 80% of all positive cases.,The prevalence of P. falciparum and P. vivax was significantly higher in subjects younger than 20 years (p ≤ 0.01).,In the present study, among non-symptomatic healthy individuals, anaemia was strongly correlated with the prevalence and load of P. falciparum infections (p ≤ 0.01; p = 0.02) and with the load of P. vivax infections (p = 0.01) as detected with real-time PCR.,Subjects with AB blood group tend to have a higher risk of being infected with P. falciparum and P. vivax when compared to other blood groups.,The present study has shown that real-time PCR provides more insight in the epidemiology of Plasmodium infections and can be used as a monitoring tool in the battle against malaria.,The unsurpassed sensitivity of real-time PCR reveals that sub microscopic infections are common in this area, which are likely to play an important role in transmission and control.,Trials number ISRCTN83830814.

Primaquine has been the only widely available hypnozoitocidal anti-malarial drug for half a century.,Despite this its clinical efficacy is poorly characterized resulting in a lack of consensus over the optimal regimen for the radical cure of Plasmodium vivax.,Published studies since 1950 of the use of primaquine regimens for preventing P. vivax relapse were reviewed.,Data were extracted systematically from available papers.,Primaquine regimens were categorized according to the total dose administered: very low (≤2.5 mg/kg), low (>2.5 mg/kg- < 5.0 mg/kg) and high (≥ 5.0 mg/kg).,The risk of recurrent infection were summarized across geographical regions and the odds ratios between treatment regimens calculated after stratifying by total treatment dose and duration of study follow up.,Data could be retrieved from 87 clinical trials presenting data in 59,735 patients enrolled into 156 treatment arms, conducted in 20 countries.,There was marked heterogeneity in study design, particularly primaquine dosing and duration of follow up.,The median rate of recurrence following very low dose of primaquine (n = 44) was 25% (range 0-90%) at 4-6 months, compared to 6.7 % (range 0-59%) following low dose primaquine (n = 82).,High dose primaquine regimens were assessed in 28 treatment arms, and were associated with a median recurrence rate of 0% (Range: 0-15%) at one month.,In 18 studies with control arms, the effectiveness of a very low dose primaquine regimen was no different from patients who did not receive primaquine (OR = 0.60, 95%CI 0.33-1.09, p = 0.09), whereas for the low dose regimens a significant difference was reported in 50% (6/12) of studies (overall OR = 0.14, 95%CI: 0.06-0.35, p < 0.001).,Two studies enrolling 171 patients demonstrated high effectiveness of high dose primaquine compared to a control arm (OR = 0.03 (95%CI: 0.01-0.13); p < 0.0001).,Low dose regimens retain adequate efficacy in some areas, but this is not uniform.,The efficacy and safety of pragmatic high dose primaquine regimens needs to be assessed in a range of endemic and geographical locations.,Such studies will require a prolonged period of follow up and comparison with control arms to account for confounding factors.

► Human hookworm infection is a leading cause of iron deficiency anemia.,► An estimated 700 million people in developing countries are affected.,► The Sabin Vaccine Institute PDP is developing the vaccine in collaboration with FIOCRUZ.,► The vaccine comprises two recombinant protein antigens on alum and a TLR4 agonist.,► The partnership's plan is that the vaccine will be licensed by 2020.,Hookworm infection is one of the world's most common neglected tropical diseases and a leading cause of iron deficiency anemia in low- and middle-income countries.,A Human Hookworm Vaccine is currently being developed by the Sabin Vaccine Institute and is in phase 1 clinical testing.,The candidate vaccine is comprised of two recombinant antigens known as Na-GST-1 and Na-APR-1, each of which is an important parasite enzyme required for hookworms to successfully utilize host blood as a source of energy.,The recombinant proteins are formulated on Alhydrogel® and are being tested in combination with a synthetic Toll-like receptor 4 agonist.,The aim of the vaccine is to induce anti-enzyme antibodies that will reduce both host blood loss and the number of hookworms attached to the gut.,Transfer of the manufacturing technology to the Oswaldo Cruz Foundation (FIOCRUZ)/Bio-Manguinhos (a Brazilian public sector developing country vaccine manufacturer) is planned, with a clinical development plan that could lead to registration of the vaccine in Brazil.,The vaccine would also need to be introduced in the poorest regions of Africa and Asia, where hookworm infection is highly endemic.,Ultimately, the vaccine could become an essential tool for achieving hookworm control and elimination, a key target in the 2012 London Declaration on Neglected Tropical Diseases.

During the pre-patent stage of infection, juvenile Schistosoma blood flukes co-opt signals from the adaptive immune system to facilitate parasite development, but the types of responses that are induced at this early stage of infection, and the parasite antigens they target, have not been characterized.,Through analysis of experimental pre-patent infections, we show that the S. mansoni cysteine protease SmCB1 is rapidly targeted by an antigen-specific IgE response.,The induction of this response is independent of schistosome eggs as infection with male or female worms alone also induced SmCB1-specific IgE.,We also show that the SmCB1-specific IgE response is dependent on cognate CD4+ T cell help and IL-4, suggesting that pre-patent Th2 responses provide T cell help for the SmCB1-specific IgE response.,Finally, exposed human subjects also produced IgE against SmCB1.,Our data demonstrate that, like eggs, schistosome worms also induce functional type 2 responses and that a parasite cysteine protease is an inducer of type 2 responses during the early stages of schistosome infection.

Malawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement of chloroquine and delayed introduction of artemisinin-based combination therapy.,Extended use of SP, and its continued application in pregnancy is impacting the genomic variation of the Plasmodium falciparum population.,Whole genome sequence data of P. falciparum isolates covering 2 years of transmission within Malawi, alongside global datasets, were used.,More than 745,000 SNPs were identified, and differences in allele frequencies between countries assessed, as well as genetic regions under positive selection determined.,Positive selection signals were identified within dhps, dhfr and gch1, all components of the parasite folate pathway associated with SP resistance.,Sitting predominantly on a dhfr triple mutation background, a novel copy number increase of ~twofold was identified in the gch1 promoter.,This copy number was almost fixed (96.8% frequency) in Malawi samples, but found at less than 45% frequency in other African populations, and distinct from a whole gene duplication previously reported in Southeast Asian parasites.,SP resistance selection pressures have been retained in the Malawian population, with known resistance dhfr mutations at fixation, complemented by a novel gch1 promoter duplication.,The effects of the duplication on the fitness costs of SP variants and resistance need to be elucidated.,The online version of this article (doi:10.1186/s12936-016-1634-6) contains supplementary material, which is available to authorized users.

Prospects for malaria eradication will be greatly enhanced by an effective vaccine, but parasite genetic diversity poses a major impediment to malaria vaccine efficacy.,In recent pre-clinical and field trials, vaccines based on polymorphic Plasmodium falciparum antigens have shown efficacy only against homologous strains, raising the specter of allele-specific immunity such as that which plagues vaccines against influenza and HIV.,The most advanced malaria vaccine, RTS,S, targets relatively conserved epitopes on the P. falciparum circumsporozoite protein.,After more than 40 years of development and testing, RTS,S, has shown significant but modest efficacy against clinical malaria in phase 2 and 3 trials.,Ongoing phase 2 studies of an irradiated sporozoite vaccine will ascertain whether the full protection against homologous experimental malaria challenge conferred by high doses of a whole organism vaccine can provide protection against diverse strains in the field.,Here we review and evaluate approaches being taken to design broadly cross-protective malaria vaccines.

The human population in the highlands of Nyanza Province, western Kenya, is subject to sporadic epidemics of Plasmodium falciparum.,Indoor residual spraying (IRS) and long-lasting insecticide treated nets (LLINs) are used widely in this area.,These interventions are most effective when Anopheles rest and feed indoors and when biting occurs at times when individuals use LLINs.,It is therefore important to test the current assumption of vector feeding preferences, and late night feeding times, in order to estimate the extent to which LLINs protect the inhabitants from vector bites.,Mosquito collections were made for six consecutive nights each month between June 2011 and May 2012.,CDC light-traps were set next to occupied LLINs inside and outside randomly selected houses and emptied hourly.,The net usage of residents, their hours of house entry and exit and times of sleeping were recorded and the individual hourly exposure to vectors indoors and outdoors was calculated.,Using these data, the true protective efficacy of nets (P*), for this population was estimated, and compared between genders, age groups and from month to month.,Primary vector species (Anopheles funestus s.l. and Anopheles arabiensis) were more likely to feed indoors but the secondary vector Anopheles coustani demonstrated exophagic behaviour (p < 0.05).,A rise in vector biting activity was recorded at 19:30 outdoors and 18:30 indoors.,Individuals using LLINs experienced a moderate reduction in their overall exposure to malaria vectors from 1.3 to 0.47 bites per night.,The P* for the population over the study period was calculated as 51% and varied significantly with age and season (p < 0.01).,In the present study, LLINs offered the local population partial protection against malaria vector bites.,It is likely that P* would be estimated to be greater if the overall suppression of the local vector population due to widespread community net use could be taken into account.,However, the overlap of early biting habit of vectors and human activity in this region indicates that additional methods of vector control are required to limit transmission.,Regular surveillance of both vector behaviour and domestic human-behaviour patterns would assist the planning of future control interventions in this region.,The online version of this article (doi:10.1186/s12936-015-0766-4) contains supplementary material, which is available to authorized users.

Malaria vector control relies on toxicity of insecticides used in long lasting insecticide treated nets and indoor residual spraying.,This is despite evidence that sub-lethal insecticides reduce human-vector contact and malaria transmission.,The impact of sub-lethal insecticides on host seeking and blood feeding of mosquitoes was measured.,Taxis boxes distinguished between repellency and attraction inhibition of mosquitoes by measuring response of mosquitoes towards or away from Transfluthrin coils and humans.,Protective effective distance of coils and long-term effects on blood feeding were measured in the semi-field tunnel and in a Peet Grady chamber.,Laboratory reared pyrethroid susceptible Anopheles gambiae sensu stricto mosquitoes were used.,In the taxis boxes, a higher proportion of mosquitoes (67%-82%) were activated and flew towards the human in the presence of Transfluthrin coils.,Coils did not hinder attraction of mosquitoes to the human.,In the semi-field Tunnel, coils placed 0.3 m from the human reduced feeding by 86% (95% CI [0.66; 0.95]) when used as a “bubble” compared to 65% (95% CI [0.51; 0.76]) when used as a “point source”.,Mosquitoes exposed to coils inside a Peet Grady chamber were delayed from feeding normally for 12 hours but there was no effect on free flying and caged mosquitoes exposed in the semi-field tunnel.,These findings indicate that airborne pyrethroids minimize human-vector contact through reduced and delayed blood feeding.,This information is useful for the development of target product profiles of spatial repellent products that can be used to complement mainstream malaria vector control tools.

Primaquine is essential for malaria control and elimination since it is the only available drug preventing multiple clinical attacks by relapses of Plasmodium vivax.,It is also the only therapy against the sexual stages of Plasmodium falciparum infectious to mosquitoes, and is thus useful in preventing malaria transmission.,However, the difficulties of diagnosing glucose-6-phosphate dehydrogenase deficiency (G6PDd) greatly hinder primaquine’s widespread use, as this common genetic disorder makes patients susceptible to potentially severe and fatal primaquine-induced haemolysis.,The risk of such an outcome varies widely among G6PD gene variants.,A literature review was conducted to identify surveys of G6PD variant frequencies among representative population groups.,Informative surveys were assembled into two map series: (1) those showing the relative proportions of the different variants among G6PDd individuals; and (2) those showing allele frequencies of G6PD variants based on population surveys without prior G6PDd screening.,Variants showed conspicuous geographic patterns.,A limited repertoire of variants was tested for across sub-Saharan Africa, which nevertheless indicated low genetic heterogeneity predominated by the G6PD A-202A mutation, though other mutations were common in western Africa.,The severe G6PD Mediterranean variant was widespread across western Asia.,Further east, a sharp shift in variants was identified, with high variant heterogeneity in the populations of China and the Asia-Pacific where no single variant dominated.,G6PD variants exhibited distinctive region-specific distributions with important primaquine policy implications.,Relative homogeneity in the Americas, Africa, and western Asia contrasted sharply with the heterogeneity of variants in China, Southeast Asia and Oceania.,These findings will inform rational risk assessments for primaquine in developing public health strategies for malaria control and elimination, and support the future development of regionally targeted policies.,The major knowledge gaps highlighted here strongly advocate for further investigation of G6PD variant diversity and their primaquine-sensitivity phenotypes.

Malaria and anaemia (Haemoglobin <11 g/dl) remain frequent in tropical regions and are closely associated.,Although anaemia aetiologies are known to be multi-factorial, most studies in malaria endemic areas have been confined to analysis of possible associations between anaemia and individual factors such as malaria.,A case control study involving children aged from 1 to 10 years was conducted to assess some assumed contributors to anaemia in the area of Bonconto Health post in Senegal.,Study participants were randomly selected from a list of children who participated in a survey in December 2010.,Children aged from 1 to 10 years with haemoglobin level below 11 g/dl represented cases (anaemic children).,Control participants were eligible if of same age group and their haemoglobin level was >= 11 g/dl.,For each participant, a physical examination was done and anthropometric data collected prior to a biological assessment which included: malaria parasitaemia infection, intestinal worm carriage, G6PD deficiency, sickle cell disorders, and alpha-talassaemia.,Three hundred and fifty two children < 10 years of age were enrolled (176 case and 176 controls).,In a logistic regression analysis, anaemia was significantly associated with malaria parasitaemia (aOR=5.23, 95%CI[1.1-28.48]), sickle cell disorders (aOR=2.89, 95%CI[1,32-6.34]), alpha-thalassemia (aOR=1.82, 95%CI[1.2-3.35]), stunting (aOR=3.37, 95%CI[1.93-5.88], age ranged from 2 to 4 years (aOR=0.13, 95%CI[0.05-0.31]) and age > 5 years (aOR=0.03, 95%CI[0.01-0.08]).,Stratified by age group, anaemia was significantly associated with stunting in children less than 5 years (aOR=3.1 95%CI[1.4 - 6.8]), with, sickle cell disorders (aOR=3.5 95%CI [1.4 - 9.0]), alpha-thalassemia (or=2.4 95%CI[1.1-5.3]) and stunting (aOR=3.6 95%CI [1.6-8.2]) for children above 5 years.,No association was found between G6PD deficiency, intestinal worm carriage and children’s gender.,Malaria parasitaemia, stunting and haemoglobin genetic disorders represented the major causes of anaemia among study participants.,Anaemia control in this area could be achieved by developing integrated interventions targeting both malaria and malnutrition.

The emergence and spread of Plasmodium falciparum and Plasmodium vivax resistance to available anti-malarial drugs represents a major drawback in the control of malaria and its associated morbidity and mortality.,The aim of this study was to evaluate the chemoresistance profile of P. falciparum and P. vivax to commonly used anti-plasmodial drugs in a malaria-endemic area in the Brazilian Amazon.,The study was carried out in Manaus (Amazonas state), in the Brazilian Amazon.,A total of 88 P. falciparum and 178 P. vivax isolates was collected from 2004 to 2007.,The sensitivity of P. falciparum isolates was determined to chloroquine, quinine, mefloquine and artesunate and the sensitivity of P. vivax isolates was determined to chloroquine and mefloquine, by using the colorimetric DELI test.,As expected, a high prevalence of P. falciparum isolates resistant to chloroquine (78.1%) was observed.,The prevalence of isolates with profile of resistance or decreased sensitivity for quinine, mefloquine and artesunate was 12.7, 21.2 and 11.7%, respectively.,In the case of P. vivax, the prevalence of isolates with profile of resistance for chloroquine and mefloquine was 9.8 and 28%, respectively.,No differences in the frequencies of isolates with profile of resistance or geometric mean IC50s were seen when comparing the data obtained in 2004, 2005, 2006 and 2007, for all tested anti-malarials.,The great majority of P. falciparum isolates in the Brazilian malaria-endemic area remain resistant to chloroquine, and the decreased sensitivity to quinine, mefloquine and artesunate observed in 10-20% of the isolates must be taken with concern, especially for artesunate.,Plasmodium vivax isolates also showed a significant proportion of isolates with decreased sensitivity to chloroquine (first-line drug) and mainly to mefloquine.,The data presented here also confirm the usefulness of the DELI test to generate results able to impact on public health policies.

Rosalind Howes and colleagues present a map of glucose-6-phosphate dehydrogenase deficiency prevalence and severity.,Individuals with the deficiency are at risk of mild to severe hemolysis when taking the antimalarial primaquine.,Primaquine is a key drug for malaria elimination.,In addition to being the only drug active against the dormant relapsing forms of Plasmodium vivax, primaquine is the sole effective treatment of infectious P. falciparum gametocytes, and may interrupt transmission and help contain the spread of artemisinin resistance.,However, primaquine can trigger haemolysis in patients with a deficiency in glucose-6-phosphate dehydrogenase (G6PDd).,Poor information is available about the distribution of individuals at risk of primaquine-induced haemolysis.,We present a continuous evidence-based prevalence map of G6PDd and estimates of affected populations, together with a national index of relative haemolytic risk.,Representative community surveys of phenotypic G6PDd prevalence were identified for 1,734 spatially unique sites.,These surveys formed the evidence-base for a Bayesian geostatistical model adapted to the gene's X-linked inheritance, which predicted a G6PDd allele frequency map across malaria endemic countries (MECs) and generated population-weighted estimates of affected populations.,Highest median prevalence (peaking at 32.5%) was predicted across sub-Saharan Africa and the Arabian Peninsula.,Although G6PDd prevalence was generally lower across central and southeast Asia, rarely exceeding 20%, the majority of G6PDd individuals (67.5% median estimate) were from Asian countries.,We estimated a G6PDd allele frequency of 8.0% (interquartile range: 7.4-8.8) across MECs, and 5.3% (4.4-6.7) within malaria-eliminating countries.,The reliability of the map is contingent on the underlying data informing the model; population heterogeneity can only be represented by the available surveys, and important weaknesses exist in the map across data-sparse regions.,Uncertainty metrics are used to quantify some aspects of these limitations in the map.,Finally, we assembled a database of G6PDd variant occurrences to inform a national-level index of relative G6PDd haemolytic risk.,Asian countries, where variants were most severe, had the highest relative risks from G6PDd.,G6PDd is widespread and spatially heterogeneous across most MECs where primaquine would be valuable for malaria control and elimination.,The maps and population estimates presented here reflect potential risk of primaquine-associated harm.,In the absence of non-toxic alternatives to primaquine, these results represent additional evidence to help inform safe use of this valuable, yet dangerous, component of the malaria-elimination toolkit.,Please see later in the article for the Editors' Summary,Malaria is a parasitic infection that is transmitted to people through the bites of infected mosquitoes.,Of the four parasites that cause malaria, Plasmodium falciparum is the most deadly and P. vivax is the commonest and most widely distributed.,Malaria parasites have a complex life cycle.,Infected mosquitoes inject “sporozoites” into people, a form of the parasite that replicates inside human liver cells.,After a few days, the liver cells release “merozoites,” which invade red blood cells where they replicate rapidly before bursting out and infecting other red blood cells.,This increase in the parasitic burden causes malaria's characteristic fever and can cause organ damage and death.,Infected red blood cells also release “gametocytes,” which infect mosquitoes when they take a blood meal.,In the mosquito, gametocytes multiply and develop into sporozoites, thus completing the parasite's life cycle.,Malaria can be prevented by controlling the mosquitoes that spread the parasite and by avoiding mosquito bites by sleeping under insecticide-treated bed nets.,Treatment with effective antimalarial drugs also decreases malaria transmission.,The Global Malaria Action Plan aims to reduce malaria deaths to zero by 2015 and to eradicate malaria in the long-term through its progressive elimination in malaria-endemic countries (countries where malaria is always present).,Primaquine is a key drug for malaria elimination.,It is the only treatment effective against the gametocytes that transmit malaria between people and mosquitoes and against P. vivax “hypnozoites,” which hibernate in the liver and cause malaria relapses.,Unfortunately, primaquine induces mild to severe destruction of red blood cells (hemolysis) in people who have a deficiency in the enzyme glucose-6-phosphate dehydrogenase (G6PD).,G6PD deficiency (G6PDd) is common in some ethnic groups but the global distribution of individuals at risk of primaquine-induced hemolysis is unknown and there is no practical field test for G6PDd.,Consequently, it is hard to design and implement primaquine treatment practices that balance the benefits of malaria transmission reduction and relapse prevention against the risk of hemolysis.,Here, the researchers use a geostatistical model to map the prevalence (frequency in a population) of G6PDd in malaria-endemic countries and to estimate how many people are affected in these countries.,They also develop a national index of relative hemolytic risk.,The researchers fed data from community surveys of the prevalence of phenotypic G6PDd (reduced enzyme activity) for 1,734 sites (including 1,289 sites in malaria-endemic countries) into a geostatistical model originally developed to map global malaria endemicity.,The model predicted that G6PDd is widespread across malaria-endemic regions, with the lowest prevalences in the Americas and the highest in tropical Africa and the Arabian Peninsula, but that most G6PDd individuals live in Asian countries.,The predicted prevalence of G6PDd varied considerably over relatively short distances in many areas but, averaged across malaria-endemic countries it was 8%, which corresponds to about 350 million affected individuals; averaged across countries that are currently planning for malaria elimination, the prevalence was 5.3% (nearly 100 million affected individuals).,Finally, the researchers used data on the geographical occurrence of G6PD variants classified according to their enzyme activity levels as mild or severe to derive an index of hemolytic risk from G6PDd for each malaria-endemic country.,The greatest risk was in the Arabian Peninsula and west Asia where the predicted prevalence of G6PDd and the occurrence of severe G6PD variants were both high.,These findings suggest that G6PDd is widespread and spatially heterogeneous across most of the malaria-endemic countries where primaquine would be valuable for malaria control and elimination.,The accuracy of these findings is limited, however, by the assumptions made in the geostatistical model, by the accuracy of the data fed into the model, and by the lack of data for some malaria-endemic countries.,Moreover, there is considerable uncertainty associated with the proposed index of hemolysis risk because it is based on phenotypic G6PDd enzyme activity classifications, which is presumed, but not widely demonstrated, to be a surrogate marker for hemolysis.,Nevertheless, these findings pave the way for further data collection and for the refinement of G6PDd maps that, in the absence of non-toxic alternatives to primaquine, will guide the design of safe primaquine regimens for the elimination of malaria.,Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001339.,Information is available from the World Health Organization on malaria; its 2011 World Malaria Report provides details of the current global malaria situation (some information is available in several languages),The US Centers for Disease Control and Prevention provide information on malaria (in English and Spanish), including a selection of personal stories about malaria,Information is available from the Roll Back Malaria Partnership on the global control of malaria and on the Global Malaria Action Plan,Information on the global mapping of malaria is available at the Malaria Atlas Project website where G6PD deficiency prevalence maps, population estimates and the data used in this study can also be accessed,Information about G6PD deficiency for affected families can be found on KidsHealth from the Nemous Children's Health System and the G6PD Deficiency Association website,MedlinePlus provides links to additional information on malaria; the MedlinePlus Encyclopedia provides information about G6PD deficiency (in English and Spanish)

Antimalarial drug resistance has historically arisen through convergent de novo mutations in Plasmodium falciparum parasite populations in Southeast Asia and South America.,For the past decade in Southeast Asia, artemisinins, the core component of first-line antimalarial therapies, have experienced delayed parasite clearance associated with several pfk13 mutations, primarily C580Y.,We report that mutant pfk13 has emerged independently in Guyana, with genome analysis indicating an evolutionary origin distinct from Southeast Asia.,Pfk13 C580Y parasites were observed in 1.6% (14/854) of samples collected in Guyana in 2016-2017.,Introducing pfk13 C580Y or R539T mutations by gene editing into local parasites conferred high levels of in vitro artemisinin resistance.,In vitro growth competition assays revealed a fitness cost associated with these pfk13 variants, potentially explaining why these resistance alleles have not increased in frequency more quickly in South America.,These data place local malaria control efforts at risk in the Guiana Shield.,All recommended treatments against malaria include a drug called artemisinin or some of its derivatives.,However, there are concerns that Plasmodium falciparum, the parasite that causes most cases of malaria, will eventually develop widespread resistance to the drug.,A strain of P. falciparum partially resistant to artemisinin was seen in Cambodia in 2008, and it has since spread across Southeast Asia.,The resistance appears to be frequently linked to a mutation known as pfk13 C580Y.,Southeast Asia and Amazonia are considered to be hotspots for antimalarial drug resistance, and the pfk13 C580Y mutation was detected in the South American country of Guyana in 2010.,To examine whether the mutation was still circulating in this part of the world, Mathieu et al. collected and analyzed 854 samples across Guyana between 2016 and 2017.,Overall, 1.6% of the samples had the pfk13 C580Y mutation, but this number was as high as 8.8% in one region.,Further analyses revealed that the mutation in Guyana had not spread from Southeast Asia, but that it had occurred in Amazonia independently.,To better understand the impact of the pfk13 C580Y mutation, Mathieu et al. introduced this genetic change into non-resistant parasites from a country neighbouring Guyana.,As expected, the mutation made P. falciparum highly resistant to artemisinin, but it also slowed the growth rate of the parasite.,This disadvantage may explain why the mutation has not spread more rapidly through Guyana in recent years.,Artemisinin and its derivatives are always associated with other antimalarial drugs to slow the development of resistance; there are concerns that reduced susceptibility to artemisinin leads to the parasites becoming resistant to the partner drugs.,Further research is needed to evaluate how the pfk13 C580Y mutation affects the parasite’s response to the typical combination of drugs that are given to patients.

Development of resistance to first line antimalarials led to recommendation of artemisinin based combination therapies (ACTs).,High adherence to ACTs provided by community health workers (CHWs) gave reassurance that community based interventions did not increase the risk of drug resistance.,Integrated community case management of illnesses (ICCM) is now recommended through which children will access both antibiotics and antimalarials from CHWs.,Increased number of medicines has been shown to lower adherence.,To compare adherence to antimalarials alone versus antimalarials combined with antibiotics under ICCM in children less than five years.,A cohort study was nested within a cluster randomized trial that had CHWs treating children less than five years with antimalarials and antibiotics (intervention areas) and CHWs treating children with antimalarials only (control areas).,Children were consecutively sampled from the CHWs' registers in the control areas (667 children); and intervention areas (323 taking antimalarials only and 266 taking antimalarials plus antibiotics).,The sampled children were visited at home on day one and four of treatment seeking.,Adherence was assessed using self reports and pill counts.,Adherence in the intervention arm to antimalarials alone and antimalarials plus antibiotics arm was similar (mean 99% in both groups) but higher than adherence in the control arm (antimalarials only) (mean 96%).,Forgetfulness (38%) was the most cited reason for non-adherence.,At adjusted analysis: absence of fever (OR = 3.3, 95%CI = 1.6-6.9), seeking care after two or more days (OR = 2.2, 95%CI = 1.3-3.7), not understanding instructions given (OR = 24.5, 95%CI = 2.7-224.5), vomiting (OR = 2.6, 95%CI = 1.2-5.5), and caregivers' perception that the child's illness was not severe (OR = 2.0, 95%CI = 1.1-3.8) were associated with non-adherence.,Addition of antibiotics to antimalarials did not lower adherence.,However, caregivers should be adequately counseled to understand the dosing regimens; continue with medicines even when the child seems to improve; and re-administer doses that have been vomited.

Cholangiocarcinoma (CCA) is an aggressive cancer arising from epithelial cells of the bile duct.,Most patients with CCA have an unresectable tumor at the time of diagnosis.,In Western countries, the risk of CCA increases in patients with primary sclerosing cholangitis, whereas liver fluke infection appears to be the major risk factor for CCA in Asian countries.,A diagnosis of liver fluke infection often relies on stool samples, including microscopic examination, polymerase chain reaction-based assays, and fluke antigen detection.,Tests of serum, saliva and urine samples are also potentially diagnostic.,The presence of liver fluke along with exogenous carcinogens magnifies the risk of CCA in people living in endemic areas.,The “liver fluke-cholangiocarcinoma” carcinogenesis pathways consist of mechanical damage to the bile duct epithelium, immunopathologic and cellular reactions to the liver fluke’s antigens and excretory/secretory products, liver fluke-induced changes in the biliary tract microbiome and the effects of repeated treatment for liver fluke.,A vaccine and novel biomarkers are needed for the primary and secondary prevention of CCA in endemic areas.,Importantly, climate change exerts an effect on vector-borne parasitic diseases, and awareness of liver fluke should be enhanced in potentially migrated habitat areas.

Marine nematodes of the genus Anisakis are common parasites of a wide range of aquatic organisms.,Public interest is primarily based on their importance as zoonotic agents of the human Anisakiasis, a severe infection of the gastro-intestinal tract as result of consuming live larvae in insufficiently cooked fish dishes.,The diverse nature of external impacts unequally influencing larval and adult stages of marine endohelminth parasites requires the consideration of both abiotic and biotic factors.,Whereas abiotic factors are generally more relevant for early life stages and might also be linked to intermediate hosts, definitive hosts are indispensable for a parasite’s reproduction.,In order to better understand the uneven occurrence of parasites in fish species, we here use the maximum entropy approach (Maxent) to model the habitat suitability for nine Anisakis species accounting for abiotic parameters as well as biotic data (definitive hosts).,The modelled habitat suitability reflects the observed distribution quite well for all Anisakis species, however, in some cases, habitat suitability exceeded the known geographical distribution, suggesting a wider distribution than presently recorded.,We suggest that integrative modelling combining abiotic and biotic parameters is a valid approach for habitat suitability assessments of Anisakis, and potentially other marine parasite species.

Primaquine is the only widely used drug that prevents Plasmodium vivax malaria relapses, but adherence to the standard 14-day regimen is poor.,We aimed to assess the efficacy of a shorter course (7 days) of primaquine for radical cure of vivax malaria.,We did a randomised, double-blind, placebo-controlled, non-inferiority trial in eight health-care clinics (two each in Afghanistan, Ethiopia, Indonesia, and Vietnam).,Patients (aged ≥6 months) with normal glucose-6-phosphate dehydrogenase (G6PD) and presenting with uncomplicated vivax malaria were enrolled.,Patients were given standard blood schizontocidal treatment and randomly assigned (2:2:1) to receive 7 days of supervised primaquine (1·0 mg/kg per day), 14 days of supervised primaquine (0·5 mg/kg per day), or placebo.,The primary endpoint was the incidence rate of symptomatic P vivax parasitaemia during the 12-month follow-up period, assessed in the intention-to-treat population.,A margin of 0·07 recurrences per person-year was used to establish non-inferiority of the 7-day regimen compared with the 14-day regimen.,This trial is registered at ClinicalTrials.gov (NCT01814683).,Between July 20, 2014, and Nov 25, 2017, 2336 patients were enrolled.,The incidence rate of symptomatic recurrent P vivax malaria was 0·18 (95% CI 0·15 to 0·21) recurrences per person-year for 935 patients in the 7-day primaquine group and 0·16 (0·13 to 0·18) for 937 patients in the 14-day primaquine group, a difference of 0·02 (−0·02 to 0·05, p=0·3405).,The incidence rate for 464 patients in the placebo group was 0·96 (95% CI 0·83 to 1·08) recurrences per person-year.,Potentially drug-related serious adverse events within 42 days of starting treatment were reported in nine (1·0%) of 935 patients in the 7-day group, one (0·1%) of 937 in the 14-day group and none of 464 in the control arm.,Four of the serious adverse events were significant haemolysis (three in the 7-day group and one in the 14-day group).,In patients with normal G6PD, 7-day primaquine was well tolerated and non-inferior to 14-day primaquine.,The short-course regimen might improve adherence and therefore the effectiveness of primaquine for radical cure of P vivax malaria.,UK Department for International Development, UK Medical Research Council, UK National Institute for Health Research, and the Wellcome Trust through the Joint Global Health Trials Scheme (MR/K007424/1) and the Bill & Melinda Gates Foundation (OPP1054404).

Malaria caused by Plasmodium vivax requires treatment of the blood‐stage infection and treatment of the hypnozoites that develop in the liver.,This is a challenge to effective case management of P vivax malaria, as well as being a more general substantial impediment to malaria control.,The World Health Organization (WHO) recommends a 14‐day drug course with primaquine, an 8‐aminoquinoline, at 0.25 mg/kg/day in most of the world (standard course), or 0.5 mg/kg/day in East Asia and Oceania (high‐standard course).,This long treatment course can be difficult to complete, and primaquine can cause dangerous haemolysis in individuals with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency, meaning that physicians may be reluctant to prescribe in areas where G6PD testing is not available.,This Cochrane Review evaluated whether more patient‐friendly alternative regimens are as efficacious as the standard regimen for radical cure ofP vivax malaria.,To assess the efficacy and safety of alternative primaquine regimens for radical cure of P vivax malaria compared to the standard or high‐standard 14 days of primaquine (0.25 or 0.5 mg/kg/day), as well as comparison of these two WHO‐recommended regimens.,We searched the Cochrane Infectious Diseases Group (CIDG) Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); and LILACS (BIREME) up to 17 December 2018.,We also searched the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov, and checked the reference lists of all studies identified by the above methods.,Randomized controlled trials (RCTs) of adults and children with P vivax malaria using any regimen of either chloroquine or an artemisinin‐based combination therapy (ACT) plus primaquine with either higher daily doses for 14 days, shorter regimens with the same total dose, or using weekly dosing regimens; compared with the usual standard regimens recommended by the WHO (0.25 or 0.5 mg/kg/day for 14 days), or a comparison of these two WHO‐recommended regimens.,Two review authors independently assessed trial eligibility and quality, and extracted data.,We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous data.,We grouped efficacy data according to length of follow‐up.,We analysed safety data where this information was included.,High‐standard 14‐day course versus standard 14‐day course,Two RCTs compared the high‐standard 14‐day regimen with the standard 14‐day regimen.,People with G6PD deficiency and pregnant or lactating women were excluded.,We do not know if there is any difference in P vivax recurrences at 6 months with 0.5 mg/kg/day primaquine therapy for 14 days compared to 0.25 mg/kg/day primaquine therapy for 14 days (with chloroquine: RR 0.82, 95% CI 0.47 to 1.43, 639 participants, very low‐certainty evidence; with chloroquine or an ACT: RR 1.11, 95% CI 0.17 to 7.09, 38 participants, very low‐certainty evidence).,No serious adverse events were reported.,We do not know whether there is a difference in adverse events with the higher dosage (very low‐certainty evidence).,0.5 mg/kg/day primaquine for 7 days versus standard 14‐day course,Five RCTs compared 0.5 mg/kg/day primaquine for 7 days with the standard 14‐day course.,There may be little or no difference in P vivax recurrences at 6 to 7 months when using the same total dose (0.5 mg/kg/day to 210 mg) over 7 days as compared to 14 days (RR 0.96, 95% CI 0.66 to 1.39; 1211 participants; low‐certainty evidence).,No serious adverse events were reported.,There may be little or no difference in the number of adverse events known to occur with primaquine between the primaquine shorter regimen as compared to the longer regimen (RR 1.06, 95% CI 0.64 to 1.76; 1154 participants; low‐certainty evidence).,We do not know whether there is any difference in the frequency of anaemia or discontinuation of treatment between groups (very low‐certainty evidence).,Three trials excluded people with G6PD deficiency, and two did not provide this information.,Pregnant and lactating women were either excluded or no details were provided regarding their inclusion or exclusion.,0.75 mg/kg primaquine/week for 8 weeks versus high‐standard course,One RCT compared weekly primaquine with the high‐standard 14‐day course.,G6PD‐deficient patients were not randomized but were included in the weekly primaquine group.,Only one G6PD‐deficient participant was detected during the trial.,We do not know whether weekly primaquine increases or decreases recurrences of P vivax compared to the 14‐day regimen at 11 months' follow‐up (RR 3.18, 95% CI 0.37 to 27.6; 122 participants; very low‐certainty evidence).,No serious adverse events and no episodes of anaemia were reported.,Three other RCTs evaluated different alternative regimens and doses of primaquine, but one of these RCTs did not have results available, and two used regimens that have not been widely used and the evidence was of very low certainty.,Although limited data were available, the analysis did not detect a difference in recurrence between the 7‐day regimen and the standard 14‐day regimen of 0.5 mg/kg/day primaquine, and no serious adverse events were reported in G6PD‐normal participants taking 0.5 mg/kg/day of primaquine.,This shorter regimen may be useful in G6PD‐normal patients if there are treatment adherence concerns.,Further large high‐quality RCTs are needed, such as the IMPROV trial, with more standardised comparison regimens and longer follow‐up to help resolve uncertainties.,16 September 2019,Update pending,Authors currently updating,The update is due to be published in December 2019.,Primaquine to cure people with Plasmodium vivax malaria: comparing dosing schedules,Plasmodium vivax malaria can sometimes cause potentially life‐threatening illness, and the infection continues to make many people unwell.,The infection includes a liver stage, and this requires primaquine to eradicate it and prevent the infection recrudescing.,However, the current dosing schedule requires 14 days of daily treatment.,What are the concerns about primaquine?,Primaquine is the only drug currently recommended to treat the liver parasites in P vivax malaria.,It can cause anaemia in people with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency, which is a relatively common genetic blood disorder.,Shorter regimens would help reduce the risk of default with the current two‐week regimen.,What does the research say?,We summarized trials that compared the World Health Organization (WHO)‐recommended primaquine regimen of 15 to 30 mg per day for 14 days with the same or higher doses of primaquine given over different lengths of time to determine whether alternative regimens were as successful as the recommended courses at preventing future episodes of P vivax malaria.,We searched for trials up to 17 December 2018, and included nine randomized controlled trials (studies in which participants are assigned to one of two or more treatment groups in a random manner) in our analysis.,When using 30 mg per day compared to 15 mg per day primaquine therapy for 14 days, we do not know if there is any difference in P vivax recurrences at 6 months (very low‐certainty evidence).,No serious side effects were reported, but it is unclear whether or not there is a difference in other side effects between doses (very low‐certainty evidence).,When using 30 mg primaquine per day for 7 days compared to 15 mg per day for 14 days, there may be no difference in P vivax recurrences at 6 to 7 months (low‐certainty evidence).,No serious adverse events were reported.,There may be no difference in the number of side effects known to occur with primaquine between the two treatment regimens (low‐certainty evidence).,We do not know whether weekly primaquine increases or decreases recurrences of P vivax compared to the 14‐day regimen at 11 months' follow‐up (very low‐certainty evidence).,Further large high‐quality RCTs are needed, such as the IMPROV trial, to help improve the certainty of the evidence around alternative regimens.,How up‐to‐date is this review?,The review authors searched for studies up to 17 December 2018.

Miltefosine (MIL) is an oral antileishmanial drug used for treatment of visceral leishmaniasis (VL) in the Indian subcontinent.,Recent reports indicate a significant decline in its efficacy with a high rate of relapse in VL as well as post kala-azar dermal leishmaniasis (PKDL).,We investigated the parasitic factors apparently involved in miltefosine unresponsiveness in clinical isolates of Leishmania donovani.,L. donovani isolated from patients of VL and PKDL at pretreatment stage (LdPreTx, n = 9), patients that relapsed after MIL treatment (LdRelapse, n = 7) and parasites made experimentally resistant to MIL (LdM30) were included in this study.,MIL uptake was estimated using liquid chromatography coupled mass spectrometry.,Reactive oxygen species and intracellular thiol content were measured fluorometrically.,Q-PCR was used to assess the differential expression of genes associated with MIL resistance.,LdRelapse parasites exhibited higher IC50 both at promastigote level (7.92 ± 1.30 μM) and at intracellular amastigote level (11.35 ± 6.48 μM) when compared with LdPreTx parasites (3.27 ± 1.52 μM) and (3.85 ± 3.11 μM), respectively.,The percent infectivity (72 hrs post infection) of LdRelapse parasites was significantly higher (80.71 ± 5.67%, P<0.001) in comparison to LdPreTx (60.44 ± 2.80%).,MIL accumulation was significantly lower in LdRelapse parasites (1.7 fold, P<0.001) and in LdM30 parasites (2.4 fold, P<0.001) when compared with LdPreTx parasites.,MIL induced ROS levels were significantly lower (p<0.05) in macrophages infected with LdRelapse while intracellular thiol content were significantly higher in LdRelapse compared to LdPreTx, indicating a better tolerance for oxidative stress in LdRelapse isolates.,Genes associated with oxidative stress, metabolic processes and transporters showed modulated expression in LdRelapse and LdM30 parasites in comparison with LdPreTx parasites.,The present study highlights the parasitic factors and pathways responsible for miltefosine unresponsiveness in VL and PKDL.

Paromomycin has recently been introduced for the treatment of visceral leishmaniasis and emergence of drug resistance can only be appropriately judged upon its long term routine use in the field.,Understanding alterations in parasite behavior linked to paromomycin-resistance may be essential to assess the propensity for emergence and spread of resistant strains.,A standardized and integrated laboratory approach was adopted to define and assess parasite fitness of both promastigotes and amastigotes using an experimentally induced paromomycin-resistant Leishmania donovani strain and its paromomycin-susceptible parent wild-type clinical isolate.,Primary focus was placed on parasite growth and virulence, two major components of parasite fitness.,The combination of in vitro and in vivo approaches enabled detailed comparison of wild-type and resistant strains for which no differences could be demonstrated with regard to promastigote growth, metacyclogenesis, in vitro infectivity, multiplication in primary peritoneal mouse macrophages and infectivity for Balb/c mice upon infection with 2 x 107 metacyclic promastigotes.,Monitoring of in vitro intracellular amastigote multiplication revealed a consistent decrease in parasite burden over time for both wild-type and resistant parasites, an observation that was subsequently also confirmed in a larger set of L. donovani clinical isolates.,Though the impact of these findings should be further explored, the study results suggest that the epidemiological implications of acquired paromomycin-resistance may remain minimal other than the loss of one of the last remaining drugs effective against visceral leishmaniasis.

Community-delivered models have been widely used to reduce the burden of malaria.,This review aimed to explore different community-delivered models and their relative effectiveness in terms of coverage and malaria-metric outcomes in order to inform the design and implementation of Community Health Worker (CHW) programmes for malaria control and elimination.,A systematic review of studies investigating the impact of community-delivered models on coverage and malaria-metric (parasitaemia and hyperparasitaemia, malaria case and mortality, anaemia, and fever) outcomes compared to non- community-delivered models was undertaken by searching in five databases of published papers and grey literature databases.,Data were extracted from studies meeting inclusion and quality criteria (assessed using relevant tools for the study design) by two independent authors.,Meta-analyses were performed where there was sufficient homogeneity in effect and stratified by community-delivered models to assess the impact of each model on coverage and malaria-metric outcomes.,28 studies were included from 7042 records identified.,The majority of studies (25/28) were performed in high transmission settings in Africa and there was heterogeneity in the type of, and interventions delivered as part of the community-delivered models.,Compared to non- community-delivered models, community-delivered models increased coverage of actual bed net usage (Relative Risk (RR) = 1.64 95% CI 1.39, 1.95), intermittent preventive treatment in pregnancy (RR = 1.36 95% CI 1.29, 1.44) and appropriate and timely treatment of febrile children, and improved malaria-metric outcomes such as malaria mortality (RR = 0.58 95% CI 0.52, 0.65).,However, the considerable heterogeneity was found in the impact of community-delivered models in reducing, parasitaemia and hyperparasitaemia prevalence, anaemia incidence, fever prevalence and malaria caseload.,Statistical comparisons of different community-delivered models were not undertaken due to the heterogeneity of the included studies in terms of method and interventions provided.,Overall, the community-delivered model is effective in improving the coverage of malaria interventions and reducing malaria-associated mortality.,The heterogeneity of the community-delivered models and their impact on malaria-metric indices suggests that evidence for context-specific solutions is required.,In particular, community-delivered models for malaria elimination, integrated with services for other common primary health problems, are yet to be evaluated.,The online version of this article (10.1186/s12936-019-2900-1) contains supplementary material, which is available to authorized users.

Burkina Faso conducted its first nationally representative household malaria survey in 2010/2011.,The survey collected among others, information on malaria interventions, treatment choices and malaria parasite prevalence in children aged 6-59 months.,In this study, Bayesian geostatistical models were employed to assess the effects of health interventions related to insecticide-treated bed nets (ITN), indoor residual spray (IRS), artemisinin-based combination therapy (ACT) coverage associated with childhood malaria parasite risk at national and sub-national level, after taking into account geographical disparities of climatic/environmental and socio-economic factors.,Several ITN coverage measures were calculated and Bayesian variable selection was used to identify the most important ones.,Parasitaemia risk depicting spatial patterns of infections were estimated.,The results show that the predicted population-adjusted parasitaemia risk ranges from 4.04 % in Kadiogo province to 82 % in Kompienga province.,The effect of ITN coverage was not important at national level; however ITNs have an important protective effect in Ouagadougou as well as in three districts in the western part of the country with high parasitaemia prevalence and low to moderate coverage.,There is a large variation in ACT coverage between the districts.,Although at national level the ACT effects on parasitaemia risk was not important, at sub-national level 18 districts around Ouagadougou deliver effective treatment.,The produced maps show great variations in parasitaemia risk across the country and identify the districts where interventions are being effective.,These outputs are valuable tools that can help improve malaria control in Burkina Faso.,The online version of this article (doi:10.1186/s12936-016-1282-x) contains supplementary material, which is available to authorized users.

Survey of patients exiting health facilities is a common way to assess consultation practices.,It is, however, unclear to what extent health professionals may change their practices when they are aware of such interviews taking place, possibly paying more attention to following recommended practices.,This so-called Hawthorne effect could have important consequences for interpreting research and programme monitoring, but has rarely been assessed.,A three-arm cluster-randomised trial of interventions to improve adherence to guidelines for the use of anti-malarial drugs was conducted in Tanzania.,Patient interviews were conducted outside health facilities on two randomly-selected days per week.,Health workers also routinely documented consultations in their ledgers.,The Hawthorne effect was investigated by comparing routine data according to whether exit interviews had been conducted on three key indicators of malaria care.,Adjusted logistic mixed-effects models were used, taking into account the dependencies within health facilities and calendar days.,Routine data were collected on 19,579 consultations in 18 facilities.,The odds of having a malaria rapid diagnostic test (RDT) result reported were 11 % higher on days when exit surveys were conducted (adjusted odds ratio 95 % CI: 0.98-1.26, p = 0.097), 17 % lower for prescribing an anti-malarial drug to patients with a negative RDT result (0.56-1.23, p = 0.343), and 27 % lower for prescribing an anti-malarial when no RDT result was reported (0.53-1.00, p = 0.052).,The effect varied with time, with a U-shaped association over the study period (p < 0.001).,We also observed a higher number of consultations recorded on days when exit-interviews were conducted (adjusted mean difference = 2.03, p < 0.001).,Although modest, there was some suggestion of better practice by health professionals on days when exit interviews were conducted.,Researchers should be aware of the potential Hawthorne effect, and take into account assessment methods when generalising findings to the ‘real word’ setting.,This effect is, however, likely to be context dependent, and further controlled evaluation across different settings should be conducted.,ClinicalTrials.gov: NCT01292707.,Registered on 29th January 2011.,The online version of this article (doi:10.1186/s12879-016-1362-0) contains supplementary material, which is available to authorized users.

While WHO recently recommended universal parasitological confirmation of suspected malaria prior to treatment, debate has continued as to whether wide-scale use of rapid diagnostic tests (RDTs) can achieve this goal.,Adherence of health service personnel to RDT results has been poor in some settings, with little impact on anti-malarial drug consumption.,The Senegal national malaria control programme introduced universal parasite-based diagnosis using malaria RDTs from late 2007 in all public health facilities.,This paper assesses the impact of this programme on anti-malarial drug consumption and disease reporting.,Nationally-collated programme data from 2007 to 2009 including malaria diagnostic outcomes, prescription of artemisinin-based combination therapy (ACT) and consumption of RDTs in public health facilities, were reviewed and compared.,Against a marked seasonal variation in all-cause out-patient visits, non-malarial fever and confirmed malaria, parasite-based diagnosis increased nationally from 3.9% of reported malaria-like febrile illness to 86.0% over a 3 year period.,The prescription of ACT dropped throughout this period from 72.9% of malaria-like febrile illness to 31.5%, reaching close equivalence to confirmed malaria (29.9% of 584873 suspect fever cases).,An estimated 516576 courses of inappropriate ACT prescription were averted.,The data indicate high adherence of anti-malarial prescribing practice to RDT results after an initial run-in period.,The large reduction in ACT consumption enabled by the move from symptom-based to parasite-based diagnosis demonstrates that effective roll-out and use of malaria RDTs is achievable on a national scale through well planned and structured implementation.,While more detailed information on management of parasite-negative cases is required at point of care level to assess overall cost-benefits to the health sector, considerable cost-savings were achieved in ACT procurement.,Programmes need to be allowed flexibility in management of these funds to address increases in other programmatic costs that may accrue from improved diagnosis of febrile disease.

Malaria control is heavily reliant on the use of insecticides that target and kill the adult female Anopheline vector.,The intensive use of insecticides of the pyrethroid class has led to widespread resistance in mosquito populations.,The intensity of pyrethroid resistance in some settings in Africa means mosquitoes can contact bednets treated with this insecticide class multiple times with minimal mortality effects.,Furthermore, both ageing and diel cycle have been shown to have large impacts on the resistance phenotype.,Together, these traits may affect other aspects of vector biology controlling the vectorial capacity or fitness of the mosquito.,Here we show that sublethal exposure of a highly resistant Anopheles coluzzii population originally from Burkina Faso to the pyrethroid deltamethrin results in large and sustained changes to transcript expression.,We identify five clear patterns in the data showing changes to transcripts relating to: DNA repair, respiration, translation, behaviour and oxioreductase processes.,Further, we highlight differential regulation of transcripts from detoxification families previously linked with insecticide resistance, in addition to clear down-regulation of the oxidative phosphorylation pathway both indicative of changes in metabolism post-exposure.,Finally, we show that both ageing and diel cycle have major effects on known insecticide resistance related transcripts.,Sub-lethal pyrethroid exposure, ageing and the diel cycle results in large-scale changes in the transcriptome of the major malaria vector Anopheles coluzzii.,Our data strongly supports further phenotypic studies on how transcriptional changes such as reduced expression of the oxidative phosphorylation pathway or pyrethroid induced changes to redox state might impact key mosquito traits, such as vectorial capacity and life history traits.,The online version contains supplementary material available at 10.1186/s12864-021-07646-7.

Malaria control in Africa is dependent upon the use insecticides but intensive use of a limited number of chemicals has led to resistance in mosquito populations.,Increased production of enzymes that detoxify insecticides is one of the most potent resistance mechanisms.,Several metabolic enzymes have been implicated in insecticide resistance but the processes controlling their expression have remained largely elusive.,Here, we show that the transcription factor Maf-S regulates expression of multiple detoxification genes, including the key insecticide metabolisers CYP6M2 and GSTD1 in the African malaria vector Anopheles gambiae.,Attenuation of this transcription factor through RNAi induced knockdown reduced transcript levels of these effectors and significantly increased mortality after exposure to the pyrethroid insecticides and DDT (permethrin: 9.2% to 19.2% (p = 0.015), deltamethrin: 3.9% to 21.6% (p = 0.036) and DDT: 1% to 11.7% (p = <0.01), whilst dramatically decreasing mortality induced by the organophosphate malathion (79.6% to 8.0% (p = <0.01)).,Additional genes regulated by Maf-S were also identified providing new insight into the role of this transcription factor in insects.,Maf-S is a key regulator of detoxification genes in Anopheles mosquitoes.,Disrupting this transcription factor has opposing effects on the mosquito’s response to different insecticide classes providing a mechanistic explanation to the negative cross resistance that has been reported between pyrethroids and organophosphates.,The online version of this article (10.1186/s12864-017-4086-7) contains supplementary material, which is available to authorized users.

Blood samples collected in epidemiological and clinical investigations and then stored, often at room temperature, as blood spots dried on a filter paper have become one of the most popular source of material for further molecular analyses of malaria parasites.,The dried blood spots are often archived so that they can be used for further retrospective investigations of parasite prevalence, or as new genetic markers come to the fore.,However, the suitability of the template obtained from dried blood spots that have been stored for long periods for DNA amplification is not known.,DNA from 267 archived blood spots collected over a period of 12 years from persons with microscopically confirmed Plasmodium falciparum infection was purified by one of two methods, Chelex and Qiagen columns.,These templates were subjected to highly sensitive nested PCR amplification targeting three parasite loci that differ in length and/or copy number.,When a 1.6 kb fragment of the parasites’ small subunit ribosomal RNA was targeted (primary amplification), the efficiency of P. falciparum detection decreased in samples archived for more than six years, reaching very low levels for those stored for more than 10 years.,Positive amplification was generally obtained more often with Qiagen-extracted templates.,P. falciparum could be detected in 32 of the 40 negative Qiagen-extracted templates when a microsatellite of about 180 bp was targeted.,The remaining eight samples gave a positive amplification when a small region of 238 bp of the higher copy number (20 to 200) mitochondrial genome was targeted.,The average length of DNA fragments that can be recovered from dried blood spots decreases with storage time.,Recovery of the DNA is somewhat improved, especially in older samples, by the use of a commercial DNA purification column, but targets larger than 1.5 kb are unlikely to be present 10 years after the initial blood collection, when the average length of the DNA fragments present is likely to be around a few hundred bp.,In conclusion, the utility of archived dried blood spots for molecular analyses decreases with storage time.

In order to control and eliminate malaria, areas of on-going transmission need to be identified and targeted for malaria control interventions.,Immediately following intense interventions, malaria transmission can become more heterogeneous if interventions are more successful in some areas than others.,Bioko Island, Equatorial Guinea, has been subject to comprehensive malaria control interventions since 2004.,This has resulted in substantial reductions in the parasite burden, although this drop has not been uniform across the island.,In 2008, filter paper blood samples were collected from 7387 people in a cross-sectional study incorporating 18 sentinel sites across Bioko, Equatorial Guinea.,Antibodies were measured to P. falciparum Apical Membrane Antigen-1 (AMA-1) by Enzyme Linked Immunosorbent Assay (ELISA).,Age-specific seropositivity rates were used to estimate seroconversion rates (SCR).,Analysis indicated there had been at least a 60% decline in SCR in four out of five regions on the island.,Changes in SCR showed a high degree of congruence with changes in parasite rate (PR) and with regional reductions in all cause child mortality.,The mean age adjusted concentration of anti-AMA-1 antibodies was mapped to identify areas where individual antibody responses were higher than expected.,This approach confirmed the North West of the island as a major focus of continuing infection and an area where control interventions need to be concentrated or re-evaluated.,Both SCR and PR revealed heterogeneity in malaria transmission and demonstrated the variable effectiveness of malaria control measures.,This work confirms the utility of serological analysis as an adjunct measure for monitoring transmission.,Age-specific seroprevalence based evidence of changes in transmission over time will be of particular value when no baseline data are available.,Importantly, SCR data provide additional evidence to link malaria control activities to contemporaneous reductions in all-cause child mortality.

Schistosomiasis is a parasitic infection that continues to be a major public health problem in many developing countries being responsible for an estimated burden of at least 1.4 million disability-adjusted life years (DALYs) in Africa alone.,Importantly, morbidity due to schistosomiasis has been greatly reduced in some parts of the world, including Zanzibar.,The Zanzibar government is now committed to eliminate urogenital schistosomiasis.,Over the next 3-5 years, the whole at-risk population will be administered praziquantel (40 mg/kg) biannually.,Additionally, snail control and behaviour change interventions will be implemented in selected communities and the outcomes and impact measured in a randomized intervention trial.,In this 5-year research study, on both Unguja and Pemba islands, urogenital schistosomiasis will be assessed in 45 communities with urine filtration and reagent strips in 4,500 schoolchildren aged 9-12 years annually, and in 4,500 first-year schoolchildren and 2,250 adults in years 1 and 5.,Additionally, from first-year schoolchildren, a finger-prick blood sample will be collected and examined for Schistosoma haematobium infection biomarkers.,Changes in prevalence and infection intensity will be assessed annually.,Among the 45 communities, 15 were randomized for biannual snail control with niclosamide, in concordance with preventive chemotherapy campaigns.,The reduction of Bulinus globosus snail populations and S. haematobium-infected snails will be investigated.,In 15 other communities, interventions triggering behaviour change have been designed and will be implemented in collaboration with the community.,A change in knowledge, attitudes and practices will be assessed annually through focus group discussions and in-depth interviews with schoolchildren, teachers, parents and community leaders.,In all 45 communities, changes in the health system, water and sanitation infrastructure will be annually tracked by standardized questionnaire-interviews with community leaders.,Additional issues potentially impacting on study outcomes and all incurring costs will be recordedand monitored longitudinally.,Elimination of schistosomiasis has become a priority on the agenda of the Zanzibar government and the international community.,Our study will contribute to identifying what, in addition to preventive chemotherapy, needs to be done to prevent, control, and ultimately eliminate schistosomiasis, and to draw lessons for current and future schistosomiasis elimination programmes in Africa and elsewhere.,ISRCTN48837681

Diagnosis of urogenital schistosomiasis in chronically infected adults is challenging but important, especially because long term infection of the bladder and urinary tract can have dire consequences.,We evaluated three tests for viable infection: detection of parasite specific DNA Dra1 fragments, haematuria and presence of parasite eggs for sensitivity (Se) and specificity (Sp).,Over 400 urine specimens collected from adult volunteers in an endemic area in Western Nigeria were assessed for haematuria then filtered in the field, the filter papers dried and later examined for eggs and DNA.,The results were stratified according to sex and age and subjected to Latent Class analysis.,Presence of Dra1 in males (Se = 100%; Sp = 100%) exceeded haematuria (Se = 87.6%: Sp = 34.7%) and detection of eggs (Se = 70.1%; Sp = 100%).,In females presence of Dra1 was Se = 100%: Sp = 100%, exceeding haematuria (Se = 86.7%: Sp = 77.0%) and eggs (Se = 70.1%; Sp = 100%).,Dra1 became undetectable 2 weeks after praziquantel treatment.,We conclude detection of Dra1 fragment is a definitive test for the presence of Schistosoma haematobium infection.

Little is known on the role played by Neotropical wild carnivores in the Trypanosoma cruzi transmission cycles.,We investigated T. cruzi infection in wild carnivores from three sites in Brazil through parasitological and serological tests.,The seven carnivore species examined were infected by T. cruzi, but high parasitemias detectable by hemoculture were found only in two Procyonidae species.,Genotyping by Mini-exon gene, PCR-RFLP (1f8/Akw21I) and kDNA genomic targets revealed that the raccoon (Procyon cancrivorus) harbored TcI and the coatis (Nasua nasua) harbored TcI, TcII, TcIII-IV and Trypanosoma rangeli, in single and mixed infections, besides four T. cruzi isolates that displayed odd band patterns in the Mini-exon assay.,These findings corroborate the coati can be a bioaccumulator of T. cruzi Discrete Typing Units (DTU) and may act as a transmission hub, a connection point joining sylvatic transmission cycles within terrestrial and arboreal mammals and vectors.,Also, the odd band patterns observed in coatis’ isolates reinforce that T. cruzi diversity might be much higher than currently acknowledged.,Additionally, we assembled our data with T. cruzi infection on Neotropical carnivores’ literature records to provide a comprehensive analysis of the infection patterns among distinct carnivore species, especially considering their ecological traits and phylogeny.,Altogether, fifteen Neotropical carnivore species were found naturally infected by T. cruzi.,Species diet was associated with T. cruzi infection rates, supporting the hypothesis that predator-prey links are important mechanisms for T. cruzi maintenance and dispersion in the wild.,Distinct T. cruzi infection patterns across carnivore species and study sites were notable.,Musteloidea species consistently exhibit high parasitemias in different studies which indicate their high infectivity potential.,Mesocarnivores that feed on both invertebrates and mammals, including the coati, a host that can be bioaccumulator of T. cruzi DTU’s, seem to take place at the top of the T. cruzi transmission chain.

Outbreaks of orally transmitted Trypanosoma cruzi continue to be reported in Brazil and are associated with a high mortality rate, mainly due to myocarditis.,This study is a detailed report on the disease progression of acute Chagas disease in 13 patients who were infected during two micro-outbreaks in two northeastern Brazilian towns.,Clinical outcomes as well as EKG and ECHO results are described, both before and after benznidazole treatment.,Fever and dyspnea were the most frequent symptoms observed.,Other clinical findings included myalgia, periorbital edema, headache and systolic murmur.,Two patients died of cardiac failure before receiving benznidazole treatment.,EKG and ECHO findings frequently showed a disturbance in ventricular repolarization and pericardial effusion.,Ventricular dysfunction (ejection fraction <55%) was present in 27.3% of patients.,After treatment, EKG readings normalized in 91.7% of patients.,Ventricular repolarization abnormalities persisted in 50% of the patients, while sinus bradycardia was observed in 18%.,The systolic ejection fraction normalized in two out of three patients with initially depressed ventricular function, while pericardial effusion disappeared.,Myocarditis is frequently found and potentially severe in patients with acute Chagas disease.,Benznidazole treatment may improve clinical symptoms, as well as EKG and ECHO findings.

Anti-malarial drugs are now mainly deployed as combination therapy (CT), primarily as a mechanism to prevent or slow the spread of resistance.,This strategy is justified by mathematical arguments that generally assume that drug ‘resistance’ is a binary all-or-nothing genetic trait.,Herein, a pharmacological, rather than a purely genetic, approach is used to investigate resistance and it is argued that this provides additional insight into the design principles of anti-malarial CTs.,It is usually suggested that half-lives of constituent drugs in a CT be matched: it appears more important that their post-treatment anti-malarial activity profiles be matched and strategies identified that may achieve this.,In particular, the considerable variation in pharmacological parameters noted in both human and parasites populations may compromise this matching and it is, therefore, essential to accurately quantify the population pharmacokinetics of the drugs in the CTs.,Increasing drug dosages will likely follow a law of diminishing returns in efficacy, i.e. a certain increase in dose will not necessarily lead to the same percent increase in efficacy.,This may allow individual drug dosages to be lowered without proportional decrease in efficacy, reducing any potential toxicity, and allowing the other drug(s) in the CT to compensate for this reduced dosage; this is a dangerous strategy which is discussed further.,Finally, pharmacokinetic and pharmacodynamic drug interactions and the role of resistance mechanisms are discussed.,This approach generated an idealized target product profile (TPP) for anti-malarial CTs.,There is a restricted pipeline of anti-malarial drugs but awareness of pharmacological design principles during the development stages could optimize CT design pre-deployment.,This may help prevent changes in drug dosages and/or regimen that have previously occurred post-deployment in most current anti-malarial drugs.

Malaria parasites elude eradication attempts both within the human host and across nations.,At the individual level, parasites evade the host immune responses through antigenic variation.,At the global level, parasites escape drug pressure through single nucleotide variants and gene copy amplification events conferring drug resistance.,Despite their importance to global health, the rates at which these genomic alterations emerge have not been determined.,We studied the complete genomes of different Plasmodium falciparum clones that had been propagated asexually over one year in the presence and absence of drug pressure.,A combination of whole-genome microarray analysis and next-generation deep resequencing (totaling 14 terabases) revealed a stable core genome with only 38 novel single nucleotide variants appearing in seventeen evolved clones (avg.,5.4 per clone).,In clones exposed to atovaquone, we found cytochrome b mutations as well as an amplification event encompassing the P. falciparum multidrug resistance associated protein (mrp1) on chromosome 1.,We observed 18 large-scale (>1 kb on average) deletions of telomere-proximal regions encoding multigene families, involved in immune evasion (9.5×10−6 structural variants per base pair per generation).,Six of these deletions were associated with chromosomal crossovers generated during mitosis.,We found only minor differences in rates between genetically distinct strains and between parasites cultured in the presence or absence of drug.,Using these derived mutation rates for P. falciparum (1.0-9.7×10−9 mutations per base pair per generation), we can now model the frequency at which drug or immune resistance alleles will emerge under a well-defined set of assumptions.,Further, the detection of mitotic recombination events in var gene families illustrates how multigene families can arise and change over time in P. falciparum.,These results will help improve our understanding of how P. falciparum evolves to evade control efforts within both the individual hosts and large populations.

The pathomechanism of Angiostrongylus vasorum infection‐associated bleeding diathesis in dogs is not fully understood.,To describe rotational thromboelastometry (ROTEM) parameters in dogs naturally infected with A. vasorum and to compare ROTEM parameters between infected dogs with and without clinical signs of bleeding.,A total of 21 dogs presented between 2013 and 2016.,Dogs with A. vasorum infection and ROTEM evaluation were retrospectively identified.,Thrombocyte counts, ROTEM parameters, clinical signs of bleeding, therapy, and survival to discharge were retrospectively retrieved from patient records and compared between dogs with and without clinical signs of bleeding.,Evaluation by ROTEM showed hyperfibrinolysis in 8 of 12 (67%; 95% CI, 40-86%) dogs with and 1 of 9 (11%; 95% CI, 2-44%) dogs without clinical signs of bleeding (P = .016).,Hyperfibrinolysis was associated with severe hypofibrinogenemia in 6 of 10 (60%; 95% CI, 31-83%) of the cases.,Hyperfibrinolysis decreased or resolved after treatment with 10-80 mg/kg tranexamic acid.,Fresh frozen plasma (range, 14-60 mL/kg) normalized follow‐up fibrinogen function ROTEM (FIBTEM) maximal clot firmness in 6 of 8 dogs (75%; 95% CI, 41-93%).,Survival to discharge was 67% (14/21 dogs; 95% CI, 46-83%) and was not different between dogs with and without clinical signs of bleeding (P = .379).,Hyperfibrinolysis and hypofibrinogenemia were identified as an important pathomechanism in angiostrongylosis‐associated bleeding in dogs.,Hyperfibrinolysis and hypofibrinogenemia were normalized by treatment with tranexamic acid and plasma transfusions, respectively.

Natural infection with a species of Angiostrongylus has been reported only once in wildcats from central Italy by Biocca in 1957.,The causative species of this infection was identified as Angiostrongylus chabaudi.,Following this report, this parasite had never been found in either wild or domestic cats.,The lungs and the pulmonary arteries of an adult female cat (Felis silvestris catus), road-killed in Sardinia, Italy, were macroscopically examined and dissected under a light microscope for the presence of parasites.,A slender nematode was detected and its morphometrical features were consistent with those of A. chabaudi.,Morphological data were supplemented by sequencing of the partial cytochrome oxidase c subunit 1 (cox1) gene, as well as the internal transcribed spacer 2 (ITS2) of the rDNA.,Nucleotide sequences displayed 99% homology with the ITS2 sequence [GenBank KM216825.1] of a specimen of Angiostrongylus sp. recovered recently from the pulmonary artery of a wildcat in Germany and 91% with cox1 sequence [GenBank GU138118.1] of Angiostrongylus vasorum.,The results of the present study indicate, for the first time, that A. chabaudi may also infect domestic cats, and thus should be considered in the diagnosis of metastrongyloid species infecting their cardio-pulmonary system.

Cystic echinococcosis (CE) is one of emerging zoonotic parasitic diseases throughout the world, having significant medical and economic importance in developing countries.,The western and northwestern China is considered as CE endemic areas.,In northeastern China’s Heilongjiang Province, the increasing number of sporadic human CE cases has attracted more and more attention.,The aims of the present study were to understand the clinical characteristics of human CE in the investigated area and to compare the coincidence rates of CT, ultrasound and serological test against the histopathology results among CE patients.,Hospital data of 183 human CE cases in the period from January 2004 to July 2013 were collected from the two largest hospitals in Heilongjiang Province.,Clinical data were analyzed, including age, gender, occupation and living residence of CE patients and localization, size and number of CE cysts as well as the diagnosis methods of CE before operation.,The results revealed that the incidence of CE reached a peak in the age group of 41-50 years.,Among the 183 CE patients, the females were observed to have a higher percentage of CE patients (60.66%, 111/183) than males (39.34%, 72/183).,The majority of CE patients were farmers, followed by workers, employees, public servants, students and so on.,CE cysts were most commonly found in the livers, with a 30 cm cyst in diameter being detected.,CT showed the highest coincidence rate (96.64%) for hepatic CE among the three common diagnosis methods (CT, ultrasound imagine and serological test) compared against the histopathology results.,This is the first retrospective analysis of human CE cases in Heilongjiang Province in recent ten years.,Clinical characteristics of human CE were described here.,CT appeared to be the most effective diagnosis method for hepatic CE.

Cystic echinococcosis (CE) is a cosmopolitan zoonosis caused by the larval cystic stage of the dog tapeworm Echinococcus granulosus.,This complex multicellular pathogen produces various antigens which modulate the host immune response and promote parasite survival and development.,The recent application of modern molecular and immunological approaches has revealed novel insights on the nature of the immune responses generated during the course of a hydatid infection, although many aspects of the Echinococcus-host interplay remain unexplored.,This paper summarizes recent developments in our understanding of the immunology and diagnosis of echinococcosis, indicates areas where information is lacking, and suggests possible new strategies to improve serodiagnosis for practical application.

Since 2000, the scale-up of malaria control interventions has substantially reduced morbidity and mortality caused by the disease globally, fuelling bold aims for disease elimination.,In tandem with increased availability of geospatially resolved data, malaria control programmes increasingly use high-resolution maps to characterise spatially heterogeneous patterns of disease risk and thus efficiently target areas of high burden.,We updated and refined the Plasmodium falciparum parasite rate and clinical incidence models for sub-Saharan Africa, which rely on cross-sectional survey data for parasite rate and intervention coverage.,For malaria endemic countries outside of sub-Saharan Africa, we produced estimates of parasite rate and incidence by applying an ecological downscaling approach to malaria incidence data acquired via routine surveillance.,Mortality estimates were derived by linking incidence to systematically derived vital registration and verbal autopsy data.,Informed by high-resolution covariate surfaces, we estimated P falciparum parasite rate, clinical incidence, and mortality at national, subnational, and 5 × 5 km pixel scales with corresponding uncertainty metrics.,We present the first global, high-resolution map of P falciparum malaria mortality and the first global prevalence and incidence maps since 2010.,These results are combined with those for Plasmodium vivax (published separately) to form the malaria estimates for the Global Burden of Disease 2017 study.,The P falciparum estimates span the period 2000-17, and illustrate the rapid decline in burden between 2005 and 2017, with incidence declining by 27·9% and mortality declining by 42·5%.,Despite a growing population in endemic regions, P falciparum cases declined between 2005 and 2017, from 232·3 million (95% uncertainty interval 198·8-277·7) to 193·9 million (156·6-240·2) and deaths declined from 925 800 (596 900-1 341 100) to 618 700 (368 600-952 200).,Despite the declines in burden, 90·1% of people within sub-Saharan Africa continue to reside in endemic areas, and this region accounted for 79·4% of cases and 87·6% of deaths in 2017.,High-resolution maps of P falciparum provide a contemporary resource for informing global policy and malaria control planning, programme implementation, and monitoring initiatives.,Amid progress in reducing global malaria burden, areas where incidence trends have plateaued or increased in the past 5 years underscore the fragility of hard-won gains against malaria.,Efforts towards elimination should be strengthened in such areas, and those where burden remained high throughout the study period.,Bill & Melinda Gates Foundation.

Malaria is a leading public health problem in Ethiopia.,Accurate diagnosis of Plasmodium infections is crucial for the reduction of malaria in tropical areas and for epidemiological studies.,The role of light microscopy (LM) as gold standard has been questioned and, therefore, new molecular methods have been developed for the detection of Plasmodium species.,The aim of the present work was to compare different malaria diagnostic methods in order to detect the most common species of Plasmodium and to broaden the knowledge of malaria prevalence in a hospital in a rural area in Ethiopia.,A cross-sectional survey of 471 individuals was carried out in a hospital in the rural area of Gambo (Ethiopia).,Blood samples were prepared for microscopic observation and collected in filter paper for Seminested-Multiplex PCR (SnM-PCR) and real time PCR (qPCR) testing.,The SnM-PCR was considered as the gold standard technique and compared with the rest.,Thus, agreement between SnM-PCR and LM was determined by calculating Kappa Statistics and correlation between LM and qPCR quantification was calculated by pair-wise correlation co-efficient.,Samples analysed by LM and SnM-PCR were positive for Plasmodium sp.,5.5% and 10.5%, respectively.,Sensitivity was 52.2% by LM and 70% by qPCR.,Correlation co-efficient between microscopy counts and qPCR densities for Plasmodium vivax was R2 = 0.586.,Prevalence was estimated at 7% (95% CI: 4.7-9.3).,Plasmodium vivax was the dominant species detected and the difference was statistically significant (χ2 = 5.121 p < 0.05).,The highest prevalence of the parasite (10.9%) was observed in age groups under 15 years old.,Accurate malaria diagnostic methods have a great effect in the reduction of the number of malaria-infected individuals.,SnM-PCR detection of malaria parasites may be a very useful complement to microscopic examination in order to obtain the real prevalence of each Plasmodium species.,Although SnM-PCR shows that it is a good tool for the determination of Plasmodium species, today light microscopy remains the only viabletool for malaria diagnosis in developing countries.,Therefore, re-inforcement in the training of microscopists is essential for making the correct diagnosis of malaria.,Plasmodium vivax was the predominant species in Gambo, a meso-endemic area for this species.

Kala-azar or visceral leishmanisis (VL) is known to be endemic in several States of India including West Bengal (WB).,Only meager information is available on the vector dynamics of its vector species, Phlebotomus argentipes particularly in relation to control measure from this State.,Hence, a pilot study was undertaken to assess the control strategy and its impact on vector in two endemic districts of WB, India.,Two villages each from the two districts, Maldah and Burdwan, were selected for the study.,Seasonal variation of sandflies was observed during pre-monsoon, post-monsoon and winter seasons.,Susceptibility test of P. argentipes against DDT and bioassay on DDT sprayed wall and on long lasting insecticide nets (LN) Perma Net® 2.0 were conducted as per the WHO standard methods.,P. argentipes density was high during March to October.,Susceptibility status of P. argentipes ranged from 40 to 61.54 per cent.,Bioassay test showed 57.89 per cent mortality against LN PermaNet®-2.0. and 50 per cent against DDT on wall within 30 min of exposure.,Despite the integrated vector management approach, the sandfly population was high in the study area.,The reason could be development of resistance in P. argentipes against DDT and low effectiveness of LN PermaNet®-2.0.,The more pragmatic step will be to conduct large studies to monitor the susceptibility level in P. argentipes against DDT.

To investigate the DDT and deltamethrin susceptibility of Phlebotomus argentipes, the vector of Leishmania donovani, responsible for visceral leishmaniasis (VL), in two countries (India and Nepal) with different histories of insecticide exposure.,Standard WHO testing procedures were applied using 4% DDT and 0.05% deltamethrin impregnated papers.,The effect of the physiological status (fed and unfed) of females on the outcome of the bioassays was assessed and the optimal time of exposure for deltamethrin was evaluated on a colony population.,Field populations from both countries were tested.,Fed and unfed females responded in a similar way.,For exposure time on field samples 60 min was adopted for both DDT and deltamethrin.,In Bihar, knockdown and mortality with DDT was respectively 20 and 43%.,In Nepal almost all sand flies were killed, except at the border with Bihar (mortality 62%).,With 0.05% deltamethrin, between 96 and 100% of the sand flies were killed in both regions.,Based on literature and present data 4% DDT and 0.05% deltamethrin seem to be acceptable discriminating concentrations to separate resistant from susceptible populations.,Resistance to DDT was confirmed in Bihar and in a border village of Nepal, but the sand flies were still susceptible in villages more inside Nepal where only synthetic pyrethroids are used for indoor spraying.,The low effectiveness of indoor spraying with DDT in Bihar to control VL can be partially explained by this resistance hence other classes of insecticides should be tested.,In both countries P. argentipes sand flies were susceptible to deltamethrin.

In general, safety data following exposure to drugs in the first trimester of pregnancy are scarce.,More specifically, data on the safety of artemisinin-based combination therapy (ACT) in pregnancy still remain limited.,Therefore, pregnant women from Choma, Zambia, who were exposed to artemether-lumefantrine (AL) for the treatment of uncomplicated malaria were followed up and evaluated in a prospective cohort study.,This report assessed the longitudinal safety outcomes of the pregnant women inadvertently exposed during the first trimester.,Participants were classified based on the drug used to treat their most recent malaria episode: artemether-lumefantrine (AL) versus sulphadoxine-pyrimethamine (SP) and/or quinine.,All enrolled women were followed up until six weeks post-delivery and the live births for 12 months.,There were 294 first trimester exposures in the observational cohort (pregnant women: AL = 150, AL and SP = 9 and SP and/or quinine = 135).,Similar rates of perinatal mortality (stillbirths and neonatal deaths) were observed for each treatment arm (AL 4.4%, SP and/or quinine 3.9%).,At delivery (newborns: AL = 135, AL and SP = 7 and SP and/or quinine = 129), the gestational age (measured using the Dubowitz total scores), length and head circumference of the newborns were similar between the two arms.,Low birth weights were reported in 10.2% (95% CI 6.0, 16.6) and 6.7% (95% CI 3.4, 12.6) of newborns in the AL and SP and/or quinine arms, respectively.,Overall development (including neurodevelopmental parameters) was similar between the two arms, both at 14 weeks and 12 months of age.,Exposure to AL and SP in the first trimester was not associated with particular safety risks such as perinatal mortality, preterm deliveries or low birth weights.,Such outcomes as well as infant neurodevelopmental parameters up to 12 months were similar between the two arms.,These findings add to the body of data suggesting that randomized clinical trials could now be the way forward to assess safety and efficacy of ACT in the first trimester of pregnancy.

Several non-governmental organisations (NGOs) are promoting the use of Artemisia annua teas as a home-based treatment for malaria in situations where conventional treatments are not available.,There has been controversy about the effectiveness and safety of this approach, but no pharmacovigilance studies or evaluations have been published to date.,A questionnaire about the cultivation of A. annua, treatment of patients, and side-effects observed, was sent to partners of the NGO Anamed in Kenya and Uganda.,Some of the respondents were then selected purposively for more in-depth semi-structured interviews.,Eighteen partners in Kenya and 21 in Uganda responded. 49% reported difficulties in growing the plant, mainly due to drought.,Overall about 3,000 cases of presumed malaria had been treated with A. annua teas in the previous year, of which about 250 were in children and 54 were in women in the first trimester of pregnancy.,The commonest problem observed in children was poor compliance due to the bitter taste, which was improved by the addition of sugar or honey.,Two miscarriages were reported in pregnant patients.,Only four respondents reported side-effects in other patients, the commonest of which was vomiting. 51% of respondents had started using A. annua tea to treat illnesses other than malaria.,Local cultivation and preparation of A. annua are feasible where growing conditions are appropriate.,Few adverse events were reported even in children and pregnant women.,Where ACT is in short supply, it would make sense to save it for young children, while using A. annua infusions to treat older patients who are at lower risk.,An ongoing pharmacovigilance system is needed to facilitate reporting of any adverse events.

Achieving a malaria-free world presents exciting scientific challenges as well as overwhelming health, equity, and economic benefits.,WHO and countries are setting ambitious goals for reducing the burden and eliminating malaria through the “Global Technical Strategy” and 21 countries are aiming to eliminate malaria by 2020.,The commitment to achieve these targets should be celebrated.,However, the need for innovation to achieve these goals, sustain elimination, and free the world of malaria is greater than ever.,Over 180 experts across multiple disciplines are engaged in the Malaria Eradication Research Agenda (malERA) Refresh process to address problems that need to be solved.,The result is a research and development agenda to accelerate malaria elimination and, in the longer term, transform the malaria community’s ability to eradicate it globally.,The malERA Refresh Consultative Panel on Health Systems and Policy Research summarize a research and development agenda to accelerate malaria elimination and eradicate globally.

The scaling up of malaria vector control efforts in Africa has resulted in changing the malaria vectorial systems across different ecological settings.,In view of the ongoing trends in vector population dynamics, abundance, species composition and parasite infectiousness, there is a need to understand vector distribution and their contribution to malaria transmission to facilitate future planning of control strategies.,We studied indoor and outdoor malaria transmission dynamics and vector population variability of Anopheles mosquitoes in Taveta district along the Kenyan Coast.,Anopheles mosquitoes were collected indoors and outdoors in 4 ecologically different villages using CDC light traps (both indoor and outdoor) and aspiration method (day resting indoors; DRI) methods.,Mosquitoes were examined for infection with P. falciparum sporozoites and blood feeding preferences using enzyme linked immunosorbent assay (ELISA).,The An. gambiae and An. funestus complexes were identified by PCR technique to determine the sibling species composition.,A total of 4,004 Anopheles mosquitoes were collected consisting of 34.9%% (n = 1,397) An. gambiae s.1., 28.1% (n = 1,124) An. funestus s.l., 33.5% (n = 1,340) An. coustani and 3.6% (n = 143) An. pharoensis.,A total of 14,654 culicine mosquitoes were collected, mainly Cx. quinquefasciatus.,Of the total Anopheles collected, 3,729 were tested for P. falciparum sporozoite infection.,The sporozoite transmission was found to be occurring both indoors and outdoors.,The overall sporozoite infectivity was 0.68% (n = 2,486) indoors and 1.29% (n = 1,243) outdoors.,Indoor and outdoor sporozoite infectivity and the vectorial systems varied across the 4 ecological villages.,Entomological inoculation rates for the 4 villages indicate that there was site-to-site variation.,In the 4 villages, Mwarusa had the highest EIRs with An. arabiensis, An. funestus and An. coustani contributing to 23.91, 11.96 and 23.91 infectious bites per person per year ib/p/year respectively.,In Kiwalwa and Njoro outdoor EIR was significantly higher than indoors.,This study shows that malaria transmission is occurring both indoors and outdoors.,The main vectors are An. arabiensis, An. funestus and An. coustani indoors while An. coustani is playing a major role in outdoor transmission.,Effective malaria control programmes, should therefore include tools that target both indoor and outdoor transmission.

Background.,Community health workers (CHWs) were trained in Burkina Faso, Nigeria, and Uganda to diagnose febrile children using malaria rapid diagnostic tests, and treat positive malaria cases with artemisinin-based combination therapy (ACT) and those who could not take oral medicines with rectal artesunate.,We quantified the impact of this intervention on private household costs for childhood febrile illness.,Methods.,Households with recent febrile illness in a young child in previous 2 weeks were selected randomly before and during the intervention and data obtained on household costs for the illness episode.,Household costs included consultation fees, registration costs, user fees, diagnosis, bed, drugs, food, and transport costs.,Private household costs per episode before and during the intervention were compared.,The intervention's impact on household costs per episode was calculated and projected to districtwide impacts on household costs.,Results.,Use of CHWs increased from 35% of illness episodes before the intervention to 50% during the intervention (P < .0001), and total household costs per episode decreased significantly in each country: from US Dollars (USD) $4.36 to USD $1.54 in Burkina Faso, from USD $3.90 to USD $2.04 in Nigeria, and from USD $4.46 to USD $1.42 in Uganda (all P < .0001).,There was no difference in the time used by the child's caregiver to care for a sick child (59% before intervention vs 51% during intervention spent ≤2 days).,Using the most recent population figures for each study district, we estimate that the intervention could save households a total of USD $29 965, USD $254 268, and USD $303 467, respectively, in the study districts in Burkina Faso, Nigeria, and Uganda.,Conclusions.,Improving access to malaria diagnostics and treatments in malaria-endemic areas substantially reduces private household costs.,The key challenge is to develop and strengthen community human resources to deliver the intervention, and ensure adequate supplies of commodities and supervision.,We demonstrate feasibility and benefit to populations living in difficult circumstances.,Clinical Trials Registration.,ISRCTN13858170.

Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa.,Understanding the effect of this control effort is vital to inform future control planning.,However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates.,Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015 and quantify the attributable effect of malaria disease control efforts.,We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015.,We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000.,Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted).,Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent.,Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.

Improved sanitation has been associated with a reduced prevalence of soil-transmitted helminth (STH) infection and has been hypothesized to prevent fecal contamination from spreading throughout the household environment.,We evaluated the effect of providing households with a pit latrine with a plastic slab and drophole cover, child feces management tools, and associated behavioral messaging on reducing STH eggs in household soil.,We collected soil samples from 2107 households (898 control and 1209 improved sanitation intervention households) that were enrolled in the WASH Benefits cluster randomized controlled trial in rural Kenya and performed a post-intervention analysis after two years of intervention exposure.,Following a pre-specified analysis plan, we combined all households that received the sanitation intervention into one group for comparison to control households.,The prevalence of STH eggs in soil was 18.9% in control households and 17.0% in intervention households.,The unadjusted prevalence ratio of total STH eggs in the intervention groups compared to the control group was 0.94 (95% CI: 0.78-1.13).,The geometric mean concentration was 0.05 eggs/g dry soil in control households and intervention households.,Unadjusted and adjusted models gave similar results.,We found use of a shared latrine, presence of a roof over the sampling area, and the number of dogs owned at baseline was associated with an increased prevalence of STH eggs in soil; the presence of a latrine that was at least 2 years old and a latrine with a covered drophole was associated with a reduction in the prevalence of STH eggs in soil.,Soil moisture content was also associated with an increased prevalence of STH eggs in soil.,Our results indicate that an intervention designed to increase access to improved latrines and child feces management tools may not be enough to impact environmental occurrence of STH in endemic areas where latrine coverage is already high.

We assessed the relationship of fecal environmental contamination and environmental enteropathy.,We compared markers of environmental enteropathy, parasite burden, and growth in 119 Bangladeshi children (≤ 48 months of age) across rural Bangladesh living in different levels of household environmental cleanliness defined by objective indicators of water quality and sanitary and hand-washing infrastructure.,Adjusted for potential confounding characteristics, children from clean households had 0.54 SDs (95% confidence interval [CI] = 0.06, 1.01) higher height-for-age z scores (HAZs), 0.32 SDs (95% CI = −0.72, 0.08) lower lactulose:mannitol (L:M) ratios in urine, and 0.24 SDs (95% CI = −0.63, 0.16) lower immunoglobulin G endotoxin core antibody (IgG EndoCAb) titers than children from contaminated households.,After adjusting for age and sex, a 1-unit increase in the ln L:M was associated with a 0.33 SDs decrease in HAZ (95% CI = −0.62, −0.05).,These results are consistent with the hypothesis that environmental contamination causes growth faltering mediated through environmental enteropathy.

The draft Global Technical Strategy for malaria aims to eliminate malaria from at least 10 countries by 2020.,Yemen and Saudi Arabia remain the last two countries on the Arabian Peninsula yet to achieve elimination.,Over the last 50 years, systematic efforts to control malaria in the Kingdom of Saudi Arabia has successfully reduced malaria cases to a point where malaria is now constrained largely to Jazan Province, the most south-western area along the Red Sea.,The progress toward elimination in this province is reviewed between 2000 and 2014.,Data were obtained from the Ministry of Health case-reporting systems, activity reports, unpublished consultants reports, and relevant scientific published papers.,Sub-provincial population data were obtained the national household censuses undertaken in 2004 and 2010.,Rainfall data were obtained from the Meteorological Department in Jazan.,Between 2000 and 2014 there were 5522 locally acquired cases of malaria and 9936 cases of imported malaria.,A significant reduction in locally acquired malaria cases was observed from 2000 to 2014, resulting in an average annual incidence (2010-2014) of 0.3 cases per 10,000 population.,Conversely imported cases, since 2000, remain consistent and higher than locally acquired cases, averaging between 250 and 830 cases per year.,The incidence of locally acquired cases is heterogeneous across the Province, with only a few health districts contributing the majority of the cases.,The overall decline in malaria case incidence can be attributed to coincidental expansion of control efforts and periods of exceptionally low rainfall.,Jazan province is poised to achieve malaria elimination.,There is a need to change from a policy of passive case detection to reactively and proactively detecting infectious reservoirs that require new approaches to surveillance.,These should be combined with advanced epidemiological tools to improve the definitions of epidemiological receptive and hotspot malaria risk mapping.,The single largest threat currently remains the risks posed by imported infections from Yemen.

As countries move toward malaria elimination, imported infections become increasingly significant as they often represent the majority of cases, can sustain transmission, cause resurgences, and lead to mortality.,Here we review and critique current methods to prevent malaria importation in countries pursuing elimination and explore methods applied in other transmission settings and to other diseases that could be transferred to support malaria elimination.,To improve intervention targeting we need a better understanding of the characteristics of populations importing infections and their patterns of migration, improved methods to reliably classify infections as imported or acquired locally, and ensure early and accurate diagnosis.,The potential for onward transmission in the most receptive and vulnerable locations can be predicted through high-resolution risk mapping that can help malaria elimination or prevention of reintroduction programs target resources.,Cross border and regional initiatives can be highly effective when based on an understanding of human and parasite movement.,Ultimately, determining the optimal combinations of approaches to address malaria importation will require an evaluation of their impact, cost effectiveness, and operational feasibility.

There is a continuing need for novel approaches to tick control in dogs.,One such approach lies in the ability of lotilaner (Credelio™), an isoxazoline with a rapid onset of action, to provide sustained efficacy against ticks.,Two studies were undertaken to confirm lotilaner’s efficacy, at the minimum dose rate of 20 mg/kg, against the three most common tick species in Europe.,In each of two studies, 16 Beagle dogs, at least 6 months old, were ranked and blocked by tick counts from infestations placed approximately 1 week before treatment.,Within blocks, dogs were randomized to receive either lotilaner flavoured chewable tablets at as close as possible to, but not less than the minimum dose rate of 20 mg/kg, or to be sham-treated controls.,Study 1 assessed lotilaner efficacy against concurrent infestations with 50 (± 6) Rhipicephalus sanguineus and 70 (± 6) Ixodes ricinus; Study 2 infestations were with 50 (± 2) Dermacentor reticulatus.,Infestations were performed on Day -2 with counts on Day 2, 48 (± 2) hours post-treatment.,Post-treatment infestations were performed on Days 7, 14, 21, 28 and 35, and ticks were counted 48 (±2) hours post-infestations.,Efficacy was determined by the percent reduction in mean live tick counts.,Control group infestations for each tick species were adequate for assessing lotilaner efficacy at all assessment times.,On Day 2 no live ticks were found on any lotilaner-treated dog.,For subsequent counts, in Study 1 lotilaner was 100% effective in eliminating live I. ricinus and R. sanguineus on all but two occasions for each tick; on each of those occasions efficacy was sustained at greater than 98.0%.,In Study 2, except for a single unattached live tick found on Day 16, efficacy against D. reticulatus was 100% at every post-treatment assessment.,The high and sustained efficacy against the three common species of ticks in Europe, R. sanguineus, I. ricinus and D. reticulatus, demonstrates that lotilaner can be a valuable tool in the treatment of canine tick infestations.,Lotilaner flavoured chewable tablets were well tolerated and effectiveness was sustained through at least 35 days.,The online version of this article (doi: 10.1186/s13071-017-2477-x) contains supplementary material, which is available to authorized users.,See Additional file 1 for the French translation of the Abstract.

With the geographical expansion of tick species and increased recognition of pathogens they transmit, there is a requirement for safe and rapidly effective control measures for dogs.,Lotilaner, a novel isoxazoline, is rapidly absorbed following administration of a flavored chewable tablet formulation (Credelio™), providing at least 98% efficacy for at least 1 month following assessments at 48 h post-treatment, and following subsequent challenges.,A study was conducted to determine the speed with which lotilaner kills ticks.,From 38 dogs, the 32 with the highest Ixodes ricinus counts from a Day -4 infestation were randomized among four groups: two groups were untreated controls, two received lotilaner tablets at a minimum dose rate of 20 mg/kg.,Infestations with I. ricinus were performed on Days -2, 7, 14, 21, 28 and 35.,Counts were completed 4 and 8 h post-treatment (Day 0), and 8 and 12 h following subsequent infestations.,All live ticks were incubated for 24 h following removal from study dogs.,At 4 h post-treatment, there was a 69.8% reduction in geometric mean live tick counts in treated dogs compared to controls.,After incubation, the reduction increased to 97.2%.,At 8 h after treatment, pre- and post-incubation reductions were 99.2 and 100%, respectively.,Following post-treatment challenges, post-incubation efficacy through Day 28 at 8 and 12 h was at least 94.3 and 98.0%, respectively, and was 85.7 and 94.2% at 8 and 12 h after the Day 35 challenge.,Mean live tick counts in the lotilaner groups were significantly lower than in the control groups at all assessments through Day 35 at 8 (t (7) ≥ 9, P < 0.0001, Days 0 to 28; t (7) = 3.54, P ≤ 0.0095, Day 35) and 12 h post-treatment and after subsequent infestations (t (7) ≥ 10, P < 0.0001, all days).,There were no treatment-related adverse events.,Lotilaner at a minimum dose rate of 20 mg/kg began to kill ticks on dogs within 4 h of treatment and efficacy was 100% within 8 h.,Lotilaner sustained a rapid kill of newly infesting I. ricinus through 35 days.,By quickly killing ticks that infest dogs, lotilaner has potential to help limit the transmission of tick-borne pathogens.,The online version of this article (10.1186/s13071-017-2467-z) contains supplementary material, which is available to authorized users.