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To examine the change in equity of insecticide-treated net (ITN) ownership among 19 malaria-endemic countries in sub-Saharan Africa before and after the launch of the Cover The Bed Net Gap initiative.,To assess change in equity in ownership of at least one ITN by households from different wealth quintiles, we used data from Demographic and Health Surveys and Malaria Indicator Surveys.,We assigned surveys conducted before the launch (2003-2008) as baseline surveys and surveys conducted between 2009-2014 as endpoint surveys.,We did country-level and pooled multicountry analyses.,Pooled analyses based on malaria transmission risk, were done by dividing geographical zones into either low- and intermediate-risk or high-risk.,To assess changes in equity, we calculated the Lorenz concentration curve and concentration index (C-index).,Out of the 19 countries we assessed, 13 countries showed improved equity between baseline and endpoint surveys and two countries showed no changes.,Four countries displayed worsened equity, two favouring the poorer households and two favouring the richer.,The multicountry pooled analysis showed an improvement in equity (baseline survey C-index: 0.11; 95% confidence interval, CI: 0.10 to 0.11; and endpoint survey C-index: 0.00; 95% CI: −0.01 to 0.00).,Similar trends were seen in both low- and intermediate-risk and high-risk zones.,The mass ITN distribution campaigns to increase coverage, linked to the launch of the Cover The Bed Net Gap initiative, have led to improvement in coverage of ITN ownership across sub-Saharan Africa with significant reduction in inequity among wealth quintiles.

After a national voucher scheme in 2004 provided pregnant women and infants with highly subsidized insecticide-treated nets (ITNs), use among children under five years (U5s) in mainland Tanzania increased from 16% in 2004 to 26.2% in 2007.,In 2008, the Ministry of Health and Social Welfare planned a catch-up campaign to rapidly and equitably deliver a free long-lasting insecticidal net (LLIN) to every child under five years in Tanzania.,The ITN Cell, a unit within the National Malaria Control Programme (NMCP), coordinated the campaign on behalf of the Ministry of Health and Social Welfare.,Government contractors trained and facilitated local government officials to supervise village-level volunteers on a registration of all U5s and the distribution and issuing of LLINs.,The registration results formed the basis for the LLIN order and delivery to village level.,Caregivers brought their registration coupons to village issuing posts during a three-day period where they received LLINs for their U5s.,Household surveys in five districts assessed ITN ownership and use immediately after the campaign.,Nine donors contributed to the national campaign that purchased and distributed 9.0 million LLINs at an average cost of $7.07 per LLIN, including all campaign-associated activities.,The campaign covered all eight zones of mainland Tanzania, the first region being covered separately during an integrated measles immunization/malaria LLIN distribution in August 2008, and was implemented one zone at a time from March 2009 until May 2010.,ITN ownership at household level increased from Tanzania's 2008 national average of 45.7% to 63.4%, with significant regional variations.,ITN use among U5s increased from 28.8% to 64.1%, a 2.2-fold increase, with increases ranging from 22.1-38.3% percentage points in different regions.,A national-level LLIN distribution strategy that fully engaged local government authorities helped avoid additional burden on the healthcare system.,Distribution costs per net were comparable to other public health interventions.,Particularly among rural residents, ITN ownership and use increased significantly for the intended beneficiaries.,The upcoming universal LLIN distribution and further behaviour change communication will further improve ITN ownership and use in 2010-2011.

To identify genetic effects modulating blood stage replication of the malarial parasite, we phenotyped a group of 25 inbred mouse strains for susceptibility to Plasmodium chabaudi chabaudi AS infection (peak parasitemia, survival).,A broad spectrum of responses was observed, with strains such as C57BL/6J being the most resistant (low parasitemia, 100% survival), and strains such as NZW/LacJ and C3HeB/FeJ being extremely susceptible (very high parasitemia and uniform lethality).,A number of strains showed intermediate phenotypes and gender specific effects, suggestive of rich genetic diversity in response to malaria in inbred strains.,An F2 progeny were generated from SM/J (susceptible) and C57BL/6J (resistant) parental strains, and was phenotyped for susceptibility to P. chabaudi chabaudi AS.,A whole genome scan in these animals identified the Char1 locus (LOD=7.40) on chromosome 9 as a key regulator of parasite density and pointed to a conserved 0.4Mb haplotype at Char1 that segregates with susceptibility/resistance to infection.,In addition, a second locus was detected in [SM/J x C57BL/6J] F2 mice on the X chromosome (LOD=4.26), which was given the temporary designation Char11.,These studies identify a conserved role of Char1 in regulating response to malaria in inbred mouse strains, and provide a prioritized 0.4Mb interval for the search of positional candidates.

Placental malaria (PM) can lead to poor neonatal outcomes, including low birthweight due to fetal growth restriction (FGR), especially when associated with local inflammation (intervillositis or IV).,The pathogenesis of PM-associated FGR is largely unknown, but in idiopathic FGR, impaired transplacental amino acid transport, especially through the system A group of amino acid transporters, has been implicated.,We hypothesized that PM-associated FGR could result from impairment of transplacental amino acid transport triggered by IV.,In a cohort of Malawian women and their infants, the expression and activity of system A (measured by Na+-dependent 14C-MeAIB uptake) were reduced in PM, especially when associated with IV, compared to uninfected placentas.,In an in vitro model of PM with IV, placental cells exposed to monocyte/infected erythrocytes conditioned medium showed decreased system A activity.,Amino acid concentrations analyzed by reversed phase ultra performance liquid chromatography in paired maternal and cord plasmas revealed specific alterations of amino acid transport by PM, especially with IV.,Overall, our data suggest that the fetoplacental unit responds to PM by altering its placental amino acid transport to maintain adequate fetal growth.,However, IV more profoundly compromises placental amino acid transport function, leading to FGR.,Our study offers the first pathogenetic explanation for FGR in PM.

The host immune response plays a critical role not only in protection from human leishmaniasis, but also in promoting disease severity.,Although candidate gene approaches in mouse models of leishmaniasis have been extremely informative, a global understanding of the immune pathways active in lesions from human patients is lacking.,To address this issue, genome-wide transcriptional profiling of Leishmania braziliensis-infected cutaneous lesions and normal skin controls was carried out.,A signature of the L. braziliensis skin lesion was defined that includes over 2,000 differentially regulated genes.,Pathway-level analysis of this transcriptional response revealed key biological pathways present in cutaneous lesions, generating a testable ‘metapathway’ model of immunopathology, and providing new insights for treatment of human leishmaniasis.

American cutaneous leishmaniasis (ACL) is a vector-transmitted infectious disease with an estimated 1.5 million new cases per year.,In Brazil, ACL represents a significant public health problem, with approximately 30,000 new reported cases annually, representing an incidence of 18.5 cases per 100,000 inhabitants.,Corte de Pedra is in a region endemic for ACL in the state of Bahia (BA), northeastern Brazil, with 500-1,300 patients treated annually.,Over the last decade, population and family-based candidate gene studies were conducted in Corte de Pedra, founded on previous knowledge from studies on mice and humans.,Notwithstanding limitations related to sample size and power, these studies contribute important genetic biomarkers that identify novel pathways of disease pathogenesis and possible new therapeutic targets.,The present paper is a narrative review about ACL immunogenetics in BA, highlighting in particular the interacting roles of the wound healing gene FLI1 with interleukin-6 and genes SMAD2 and SMAD3 of the transforming growth factor beta signalling pathway.,This research highlights the need for well-powered genetic and functional studies on Leishmania braziliensis infection as essential to define and validate the role of host genes in determining resistance/susceptibility regarding this disease.

Interleukin-4 receptor (IL-4Rα) is critical for the initiation of type-2 immune responses and implicated in the pathogenesis of experimental schistosomiasis.,IL-4Rα mediated type-2 responses are critical for the control of pathology during acute schistosomiasis.,However, type-2 responses tightly associate with fibrogranulomatous inflammation that drives host pathology during chronic schistosomiasis.,To address such controversy on the role of IL-4Rα, we generated a novel inducible IL-4Rα-deficient mouse model that allows for temporal knockdown of il-4rα gene after oral administration of Tamoxifen.,Interrupting IL-4Rα mediated signaling during the acute phase impaired the development of protective type-2 immune responses, leading to rapid weight loss and premature death, confirming a protective role of IL-4Rα during acute schistosomiasis.,Conversely, IL-4Rα removal at the chronic phase of schistosomiasis ameliorated the pathological fibro-granulomatous pathology and reversed liver scarification without affecting the host fitness.,This amelioration of the morbidity was accompanied by a reduced Th2 response and increased frequencies of FoxP3+ Tregs and CD1dhiCD5+ Bregs.,Collectively, these data demonstrate that IL-4Rα mediated signaling has two opposing functions during experimental schistosomiasis depending on the stage of advancement of the disease and indicate that interrupting IL-4Rα mediated signaling is a viable therapeutic strategy to ameliorate liver fibroproliferative pathology in diseases like chronic schistosomiasis.

Despite effective chemotherapy to treat schistosome infections, re-infection rates are extremely high.,Resistance to reinfection can develop, however it typically takes several years following numerous rounds of treatment and re-infection, and often develops in only a small cohort of individuals.,Using a well-established and highly permissive mouse model, we investigated whether immunoregulatory mechanisms influence the development of resistance.,Following Praziquantel (PZQ) treatment of S. mansoni infected mice we observed a significant and mixed anti-worm response, characterized by Th1, Th2 and Th17 responses.,Despite the elevated anti-worm response in PBMC's, liver, spleen and mesenteric lymph nodes, this did not confer any protection from a secondary challenge infection.,Because a significant increase in IL-10-producing CD4+CD44+CD25+GITR+ lymphocytes was observed, we hypothesised that IL-10 was obstructing the development of resistance.,Blockade of IL-10 combined with PZQ treatment afforded a greater than 50% reduction in parasite establishment during reinfection, compared to PZQ treatment alone, indicating that IL-10 obstructs the development of acquired resistance.,Markedly enhanced Th1, Th2 and Th17 responses, worm-specific IgG1, IgG2b and IgE and circulating eosinophils characterized the protection.,This study demonstrates that blocking IL-10 signalling during PZQ treatment can facilitate the development of protective immunity and provide a highly effective strategy to protect against reinfection with S. mansoni.

Increasing pyrethroid resistance in malaria vectors has been reported in western Kenya where long lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the mainstays of vector control.,To ensure the sustainability of insecticide-based malaria vector control, monitoring programs need to be implemented.,This study was designed to investigate the extent and distribution of pyrethroid resistance in 4 Districts of western Kenya (Nyando, Rachuonyo, Bondo and Teso).,All four Districts have received LLINs while Nyando and Rachuonyo Districts have had IRS campaigns for 3-5 years using pyrethroids.,This study is part of a programme aimed at determining the impact of insecticide resistance on malaria epidemiology.,Three day old adult mosquitoes from larval samples collected in the field, were used for bioassays using the WHO tube bioassay, and mortality recorded 24 hours post exposure.,Resistance level was assigned based on the 2013 WHO guidelines where populations with <90% mortality were considered resistant.,Once exposed, samples were identified to species using PCR.,An. arabiensis comprised at least 94% of all An. gambiae s.l. in Bondo, Rachuonyo and Nyando.,Teso was a marked contrast case with 77% of all samples being An. gambiae s.s.,Mortality to insecticides varied widely between clusters even in one District with mortality to deltamethrin ranging from 45-100%, while to permethrin the range was 30-100%.,Mortality to deltamethrin in Teso District was < 90% in 4 of 6 clusters tested in An arabiensis and <90% in An. gambiae s.s in 5 of 6 clusters tested.,To permethrin, mortality ranged between 5.9-95%, with <90% mortality in 9 of 13 and 8 of 13 in An. arabiensis and An. gambiae s.s. respectively.,Cluster specific mortality of An. arabiensis between permethin and deltamethrin were not correlated (Z = 2.9505, P = 0.2483).,High levels of pyrethroid resistance were observed in western Kenya.,This resistance does not seem to be associated with either species or location.,Insecticide resistance can vary within small geographical areas and such heterogeneity may make it possible to evaluate the impact of resistance on malaria and mosquito parameters within similar eco-epidemiological zones.

Anopheles gambiae s.s., Anopheles arabiensis, and Anopheles funestus s.s. are the most important species for malaria transmission.,Pyrethroid resistance of these vector mosquitoes is one of the main obstacles against effective vector control.,The objective of the present study was to monitor the pyrethroid susceptibility in the 3 major malaria vectors in a highly malaria endemic area in western Kenya and to elucidate the mechanisms of pyrethroid resistance in these species.,Gembe East and West, Mbita Division, and 4 main western islands in the Suba district of the Nyanza province in western Kenya were used as the study area.,Larval and adult collection and bioassay were conducted, as well as the detection of point mutation in the voltage-gated sodium channel (1014L) by using direct DNA sequencing.,A high level of pyrethroid resistance caused by the high frequency of point mutations (L1014S) was detected in An. gambiae s.s.,In contrast, P450-related pyrethroid resistance seemed to be widespread in both An. arabiensis and An. funestus s.s.,Not a single L1014S mutation was detected in these 2 species.,A lack of cross-resistance between DDT and permethrin was also found in An. arabiensis and An. funestus s.s., while An. gambiae s.s. was resistant to both insecticides.,It is noteworthy that the above species in the same area are found to be resistant to pyrethroids by their unique resistance mechanisms.,Furthermore, it is interesting that 2 different resistance mechanisms have developed in the 2 sibling species in the same area individually.,The cross resistance between permethrin and DDT in An. gambiae s.s. may be attributed to the high frequency of kdr mutation, which might be selected by the frequent exposure to ITNs.,Similarly, the metabolic pyrethroid resistance in An. arabiensis and An. funestus s.s. is thought to develop without strong selection by DDT.

Lymphatic filariasis is a debilitating neglected tropical disease that affects impoverished communities.,Rapid diagnostic tests of antigenaemia are a practical alternative to parasitological tests of microfilaraemia for mapping and surveillance.,However the relationship between these two methods of measuring burden has previously been difficult to interpret.,A statistical model of the distribution of worm burden and microfilariae (mf) and resulting antigenaemic and mf prevalence was developed and fitted to surveys of two contrasting sentinel sites undergoing interventions.,The fitted model was then used to explore the relationship in various pre- and post-intervention scenarios.,The model had good quantitative agreement with the data and provided estimates of the reduction in mf output due to treatment.,When extrapolating the results to a range of prevalences there was good qualitative agreement with published data.,The observed relationship between antigenamic and mf prevalence is a natural consequence of the relationship between prevalence and intensity of adult worms and mf production.,The method described here allows the estimation of key epidemiological parameters and consequently gives insight into the efficacy of an intervention programme.

Although accurate assessment of the prevalence of Schistosoma mansoni is important for the design and evaluation of control programs, the most widely used tools for diagnosis are limited by suboptimal sensitivity, slow turn-around-time, or inability to distinguish current from former infections.,Recently, two tests that detect circulating cathodic antigen (CCA) in urine of patients with schistosomiasis became commercially available.,As part of a larger study on schistosomiasis prevalence in young children, we evaluated the performance and diagnostic accuracy of these tests-the carbon test strip designed for use in the laboratory and the cassette format test intended for field use.,In comparison to 6 Kato-Katz exams, the carbon and cassette CCA tests had sensitivities of 88.4% and 94.2% and specificities of 70.9% and 59.4%, respectively.,However, because of the known limitations of the Kato-Katz assay, we also utilized latent class analysis (LCA) incorporating the CCA, Kato-Katz, and schistosome-specific antibody results to determine their sensitivities and specificities.,The laboratory-based CCA test had a sensitivity of 91.7% and a specificity of 89.4% by LCA while the cassette test had a sensitivity of 96.3% and a specificity of 74.7%.,The intensity of the reaction in both urine CCA tests reflected stool egg burden and their performance was not affected by the presence of soil transmitted helminth infections.,Our results suggest that urine-based assays for CCA may be valuable in screening for S. mansoni infections.

Plasmodium vivax infections commonly contain multiple genetically distinct parasite clones.,The detection of multiple-clone infections depends on several factors, such as the accuracy of the genotyping method, and the type and number of the molecular markers analysed.,Characterizing the multiplicity of infection has broad implications that range from population genetic studies of the parasite to malaria treatment and control.,This study compared and evaluated the efficiency of neutral and non-neutral markers that are widely used in studies of molecular epidemiology to detect the multiplicity of P. vivax infection.,The performance of six markers was evaluated using 11 mixtures of DNA with well-defined proportions of two different parasite genotypes for each marker.,These mixtures were generated by mixing cloned PCR products or patient-derived genomic DNA.,In addition, 51 samples of natural infections from the Brazil were genotyped for all markers.,The PCR-capillary electrophoresis-based method was used to permit direct comparisons among the markers.,The criteria for differentiating minor peaks from artifacts were also evaluated.,The analysis of DNA mixtures showed that the tandem repeat MN21 and the polymorphic blocks 2 (msp1B2) and 10 (msp1B10) of merozoite surface protein-1 allowed for the estimation of the expected ratio of both alleles in the majority of preparations.,Nevertheless, msp1B2 was not able to detect the majority of multiple-clone infections in field samples; it identified only 6 % of these infections.,The merozoite surface protein-3 alpha and microsatellites (PvMS6 and PvMS7) did not accurately estimate the relative clonal proportions in artificial mixtures, but the microsatellites performed well in detecting natural multiple-clone infections.,Notably, the use of a less stringent criterion to score rare alleles significantly increased the sensitivity of the detection of multi-clonal infections.,Depending on the type of marker used, a considerable amplification bias was observed, which may have serious implications for the characterization of the complexity of a P. vivax infection.,Based on the performance of markers in artificial mixtures of DNA and natural infections, a minimum panel of four genetic markers (PvMS6, PvMS7, MN21, and msp1B10) was defined, and these markers are highly informative regarding the genetic variability of P. vivax populations.,The online version of this article (doi:10.1186/s12936-015-0846-5) contains supplementary material, which is available to authorized users.

The diversity of MSP1 in both Plasmodium falciparum and P. vivax is presumed be associated to parasite immune evasion.,In this study, we assessed genetic diversity of the most variable domain of vaccine candidate N-terminal PvMSP1 (Block 2) in field isolates of Manaus.,Forty-seven blood samples the polymorphism of PvMSP1 Block 2 generates four fragment sizes.,In twenty-eight of them, sequencing indicated seven haplotypes of PvMSP1 Block 2 circulating among field isolates.,Evidence of striking exchanges was observed with two stretches flanking the repeat region and two predicted recombination sites were described.,Single nucleotide polymorphisms determined with concurrent infections per patient indicated that nonsynonymous substitutions occurred preferentially in the repeat-rich regions which also were predicted as B-cell epitopes.,The comprehensive understanding of the genetic diversity of the promising Block 2 associated with clinical immunity and a reduced risk of infection by Plasmodium vivax would be important for the rationale of malaria vaccine designs.

In an effort to improve surveillance for epidemiological and clinical outcomes, rapid diagnostic tests (RDTs) have become increasingly widespread as cost-effective and field-ready methods of malaria diagnosis.,However, there are concerns that using RDTs specific to Plasmodium falciparum may lead to missed detection of other malaria species such as Plasmodium malariae and Plasmodium ovale.,Four hundred and sixty six samples were selected from children under 5 years old in the Democratic Republic of the Congo (DRC) who took part in a Demographic and Health Survey (DHS) in 2013-14.,These samples were first tested for all Plasmodium species using an 18S ribosomal RNA-targeted real-time PCR; malaria-positive samples were then tested for P. falciparum, P. malariae and P.ovale using a highly sensitive nested PCR.,The prevalence of P. falciparum, P. malariae and P. ovale were 46.6, 12.9 and 8.3 %, respectively.,Most P. malariae and P. ovale infections were co-infected with P. falciparum-the prevalence of mono-infections of these species were only 1.0 and 0.6 %, respectively.,Six out of these eight mono-infections were negative by RDT.,The prevalence of P. falciparum by the more sensitive nested PCR was higher than that found previously by real-time PCR.,Plasmodium malariae and P. ovale remain endemic at a low rate in the DRC, but the risk of missing malarial infections of these species due to falciparum-specific RDT use is low.,The observed prevalence of P. falciparum is higher with a more sensitive PCR method.,The online version of this article (doi:10.1186/s12936-016-1409-0) contains supplementary material, which is available to authorized users.

Accurate identification of Plasmodium infections in non-endemic countries is of critical importance with regard to the administration of a targeted therapy having a positive impact on patient health and management and allowing the prevention of the risk of re-introduction of endemic malaria in such countries.,Malaria is no longer endemic in Italy where it is the most commonly imported disease, with one of the highest rates of imported malaria among European non-endemic countries including France, the UK and Germany, and with a prevalence of 24.3% at the University Hospital of Parma.,Molecular methods showed high sensitivity and specificity and changed the epidemiology of imported malaria in several non-endemic countries, highlighted a higher prevalence of Plasmodium ovale, Plasmodium vivax and Plasmodium malariae underestimated by microscopy and, not least, brought to light both the existence of two species of P. ovale (Plasmodium ovale curtisi and Plasmodium ovale wallikeri) and the infection in humans by Plasmodium knowlesi, otherwise not detectable by microscopy.,In this retrospective study an evaluation of two real-time PCR assays able to identify P. ovale wallikeri, distinguishing it from P. ovale curtisi, and to detect P. knowlesi, respectively, was performed applying them on a subset of 398 blood samples belonging to patients with the clinical suspicion of malaria.,These assays revealed an excellent analytical sensitivity and no cross-reactivity versus other Plasmodium spp. infecting humans, suggesting their usefulness for an accurate and complete diagnosis of imported malaria.,Among the 128 patients with malaria, eight P. ovale curtisi and four P. ovale wallikeri infections were detected, while no cases of P. knowlesi infection were observed.,Real-time PCR assays specific for P. ovale wallikeri and P. knowlesi were included in the panel currently used in the University Hospital of Parma for the diagnosis of imported malaria, accomplishing the goal of adhering to the recommendations of the World Health Organization to countries that are malaria-free to include the improvement of the early diagnosis of all cases of imported malaria.

Reactive case detection (RCD) is a commonly used strategy for malaria surveillance and response in elimination settings.,Many approaches to RCD assume detectable infections are clustered within and around homes of passively detected cases (index households), which has been evaluated in a number of settings with disparate results.,Household questionnaires and diagnostic testing were conducted following RCD investigations in Zanzibar, Tanzania, including the index household and up to 9 additional neighboring households.,Of 12,487 participants tested by malaria rapid diagnostic test (RDT), 3·2% of those residing in index households and 0·4% of those residing in non-index households tested positive (OR = 8·4; 95%CI: 5·7, 12·5).,Of 6,281 participants tested by quantitative polymerase chain reaction (qPCR), 8·4% of those residing in index households and 1·3% of those residing in non-index households tested positive (OR = 7·1; 95%CI: 6·1, 10·9).,Within households of index cases defined as imported, odds of qPCR-positivity amongst members reporting recent travel were 1·4 times higher than among those without travel history (95%CI: 0·2, 4·4).,Amongst non-index households, odds of qPCR-detectable infection were no different between households located within 50 m of the index household as compared with those located farther away (OR = 0·8, 95%CI: 0·5, 1·4).,Sensitivity of RDT to detect qPCR-detectable infections was 34% (95%CI: 26·4, 42·3).,Malaria prevalence in index households in Zanzibar is much higher than in non-index households, in which prevalence is very low.,Travelers represent a high-risk population.,Low sensitivity of RDTs due to a high prevalence of low-density infections results in an RCD system missing a large proportion of the parasite reservoir.

By sustaining transmission or causing malaria outbreaks, imported malaria undermines malaria elimination efforts.,Few studies have examined the impact of travel on malaria epidemiology.,We conducted a literature review and meta-analysis of studies investigating travel as a risk factor for malaria infection in sub-Saharan Africa using PubMed.,We identified 22 studies and calculated a random-effects meta-analysis pooled odds ratio (OR) of 3.77 (95% CI: 2.49-5.70), indicating that travel is a significant risk factor for malaria infection.,Odds ratios were particularly high in urban locations when travel was to rural areas, to more endemic/high transmission areas, and in young children.,Although there was substantial heterogeneity in the magnitude of association across the studies, the pooled estimate and directional consistency support travel as an important risk factor for malaria infection.

Malaria control interventions have been scaled-up in Zambia in conjunction with a malaria surveillance system.,Although substantial progress has been achieved in reducing morbidity and mortality, national and local information demonstrated marked heterogeneity in the impact of malaria control across the country.,This study reports the high burden of malaria in Nchelenge District, Luapula Province, Zambia from 2006 to 2012 after seven years of control measures.,Yearly aggregated information on cases of malaria, malaria deaths, use of malaria diagnostics, and malaria control interventions from 2006 to 2012 were obtained from the Nchelenge District Health Office.,Trends in the number of malaria cases, methods of diagnosis, malaria positivity rate among pregnant women, and intervention coverage were analysed using descriptive statistics.,Malaria prevalence remained high, increasing from 38% in 2006 to 53% in 2012.,Increasing numbers of cases of severe malaria were reported until 2010.,Intense seasonal malaria transmission was observed with seasonal declines in the number of cases between April and August, although malaria transmission continued throughout the year.,Clinical diagnosis without accompanying confirmation declined from 95% in 2006 to 35% in 2012.,Intervention coverage with long-lasting insecticide-treated nets and indoor residual spraying increased from 2006 to 2012.,Despite high coverage with vector control interventions, the burden of malaria in Nchelenge District, Zambia remained high.,The high parasite prevalence could accurately reflect the true burden, perhaps in part as a consequence of population movement, or improved access to care and case reporting.,Quality information at fine spatial scales will be critical for targeting effective interventions and measurement of progress.

Intermittent preventive treatment in infants with sulphadoxine-pyrimethamine (IPTi-SP) reduces malaria morbidity by 20% to 33%.,Potentially, however, this intervention may compromise the acquisition of immunity, including the tolerance towards multiple infections with Plasmodium falciparum.,Plasmodium falciparum isolates were obtained from children participating in two Ghanaian IPTi-SP trials (Tamale, Afigya Sekyere) at 15 months of age, i.e., six months after they had received the second dose of IPTi-SP or placebo.,By typing the polymorphic merozoite surface protein 1 (msp1) and msp2 genes, multiplicity of infection (MOI) was assessed in 389 isolates.,A total of additional 133 samples were collected in Tamale at 3, 6, 9, and 12 months of age.,Comparisons of MOI between groups were done by non-parametric statistical tests.,The number of distinguishable P. falciparum clones (MOI) ranged between one and six.,Mean MOI in Tamale was stable at 2.13 - 2.17 during the first year of life, and increased to 2.57 at age 15 months (P = 0.01).,At no age did MOI differ between the IPTi-SP and placebo groups (each, P ≥ 0.5).,At 15 months of age, i.e., six months after the second dose, MOI was very similar for children who had received IPTi or placebo (means, 2.25 vs.,2.33; P = 0.55) as was the proportion of polyclonal infections (69.6% vs.,69.7%; P = 0.99).,Adjusting for study site, current and prior malaria, parasite density, and season did not change this finding.,IPTi-SP appears to have no impact on the multiplicity of infection during infancy and thereafter.,This suggests that tolerance of multiple infections, a component of protective immunity in highly endemic areas, is not affected by this intervention.

Malaria in pregnancy (MiP) remains a major public health challenge in areas of high malaria transmission.,Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended to prevent the adverse consequences of MiP.,The effectiveness of SP for IPTp may be reduced in areas where the dhps581 mutation (a key marker of high level SP resistance) is found; this mutation was previously reported to be common in the Tanga Region of northern Tanzania, but there are limited data from other areas.,The frequency of molecular markers of SP resistance was investigated in malaria parasites from febrile patients at health centres (HC) in seven regions comprising the Lake and Southern Zones of mainland Tanzania as part of the ongoing efforts to generate national-wide data of SP resistance.,A cross-sectional survey was conducted in the outpatient departments of 14 HCs in seven regions from April to June, 2015. 1750 dried blood spot (DBS) samples were collected (117 to 160 per facility) from consenting patients with positive rapid diagnostic tests for malaria, and no recent (within past 2 months) exposure to SP or related drugs.,DNA was extracted from the DBS, pooled by HC, and underwent pooled targeted amplicon deep sequencing to yield estimates of mutated parasite allele frequency at each locus of interest.,The dhps540 mutation was common across all 14 sites, ranging from 55 to 98.4% of sequences obtained.,Frequency of the dhps581 mutation ranged from 0 to 2.4%, except at Kayanga HC (Kagera Region, Lake Zone) where 24.9% of sequences obtained were mutated.,The dhfr164 mutation was detected only at Kanyanga HC (0.06%).,By pooling DNA extracts, the allele frequency of mutations in 14 sites could be directly determined on a single deep-sequencing run.,The dhps540 mutant was very common at all locations.,Surprisingly, the dhps581 was common at one health center, but rare in all the others, suggesting that there is geographic micro-heterogeneity in mutant distribution and that accurate surveillance requires inclusion of multiple sites.,A better understanding of the effect of the dhps581 mutant on the efficacy of IPTp-SP is needed.

We describe development of an absolute multiplex quantitative real-time PCR for detection of Plasmodium spp., P. falciparum and P. vivax targets in order to produce an assay amenable to high throughput but with reduced costs.,Important qPCR experimental details and information that is critical to performance and reliability of assay results were investigated.,Inhibition studies were performed to test and compare co-purification of PCR inhibitors in samples extracted from whole blood using either the manual or automated methods.,To establish the most optimal qPCR reaction volume, volume titration of the reaction master mix was performed starting at 10 µl to 1 µl reaction master mix with 1 µl of template DNA in each reaction.,As the reaction volume decreased, qPCR assays became more efficient with 1 µl reaction master mix being the most efficient.,For more accurate quantification of parasites in a sample, we developed plasmid DNAs for all the three assay targets for absolute quantification.,All of absolute qPCR assays performed with efficiency of more than 94%, R2 values greater than 0.99 and the STDEV of each replicate was <0.167.,Linear regression plots generated from absolute qPCR assays were used to estimate the corresponding parasite density from relative qPCR in terms of parasite/µl.,One copy of plasmid DNA was established to be equivalent to 0.1 parasite/µl for Plasmodium spp. assay, 0.281 parasites for P. falciparum assay and 0.127 parasite/µl for P. vivax assay.,This study demonstrates for the first time use of plasmid DNA in absolute quantification of malaria parasite.,The use of plasmid DNA standard in quantification of malaria parasite will be critical as efforts are underway to harmonize molecular assays used in diagnosis of malaria.

The study aimed to determine the prevalence of malaria in Halaba special district, Southern Ethiopia, from 2013 to 2017.,Of a total 583,668 malaria suspected cases examined during the study period, 55,252 (9.5%) were microscopically confirmed to be positive for malaria, at the rate of 27,712 (50.2%) females and 27,540 (49.8%) males (P = 0.95).,The highest prevalence of 8454 (15.3%) malaria cases were observed in Halaba health center, followed by Halaba district hospital, at 7290 (13.2%), while the lowest cases, 1765 (3.2%), were confirmed in Wejago health center.,The highest prevalence of malaria, 25,716 (46.5%), was registered among the age group ≥ 15 year old (P = 0.006).,Plasmodium vivax and Plasmodium falciparum were the two major malaria parasites detected in this study, with the prevalence of 33,855 (62.3%) and 21,397 (38.7%), respectively (P = 0.0001).,The detected high prevalence of P. vivax in this study may clearly indicate that more attention has been given to control P. falciparum strains in the study area.,This may be a great challenge for the achievement of malaria elimination goals.,Therefore, all concerned bodies should act collaboratively to combat the high prevalence of P. vivax from the study district.

Plasmodium vivax is the most widespread human malaria, putting 2.5 billion people at risk of infection.,Its unique biological and epidemiological characteristics pose challenges to control strategies that have been principally targeted against Plasmodium falciparum.,Unlike P. falciparum, P. vivax infections have typically low blood-stage parasitemia with gametocytes emerging before illness manifests, and dormant liver stages causing relapses.,These traits affect both its geographic distribution and transmission patterns.,Asymptomatic infections, high-risk groups, and resulting case burdens are described in this review.,Despite relatively low prevalence measurements and parasitemia levels, along with high proportions of asymptomatic cases, this parasite is not benign.,Plasmodium vivax can be associated with severe and even fatal illness.,Spreading resistance to chloroquine against the acute attack, and the operational inadequacy of primaquine against the multiple attacks of relapse, exacerbates the risk of poor outcomes among the tens of millions suffering from infection each year.,Without strategies accounting for these P. vivax-specific characteristics, progress toward elimination of endemic malaria transmission will be substantially impeded.

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.

Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities.,In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa.,We performed systematic searches of electronic databases PubMed and EMBASE for relevant data using search terms ‘schistosomiasis’, ‘dosing’ and ‘praziquantel’ and hand searches of personal collections and bibliographies of recovered articles.,In 10 reports meeting study criteria, improvements in parasitological treatment outcomes after two doses of praziquantel were greater for S. mansoni infection than for S. haematobium infection.,Observed cure rates (positive to negative conversion in egg detection assays) were, for S. mansoni, 69-91% cure after two doses vs. 42-79% after one dose and, for S. haematobium, 46-99% cure after two doses vs. 37-93% after a single dose.,Treatment benefits in terms of reduction in intensity (mean egg count) were also different for the two species-for S. mansoni, the 2-dose regimen yielded an weighted average 89% reduction in standardized egg counts compared to a 83% reduction after one dose; for S. haematobium, two doses gave a 93% reduction compared to a 94% reduction with a single dose.,Cost-effectiveness analysis was performed based on Markov life path modeling.,Although schedules for repeated treatment with praziquantel require greater inputs in terms of direct costs and community participation, there are incremental benefits to this approach at an estimated cost of $153 (S. mansoni)-$211 (S. haematobium) per additional lifetime QALY gained by double treatment in school-based programs.,More rapid reduction of infection-related disease may improve program adherence, and if, as an externality of the program, transmission can be reduced through more effective coverage, significant additional benefits are expected to accrue in the targeted communities.

A nationwide, school, malaria survey was implemented to assess the risk factors of malaria prevalence and bed net use among primary school children in mainland Tanzania.,This allowed the mapping of malaria prevalence at council level and assessment of malaria risk factors among school children.,A cross-sectional, school, malaria parasitaemia survey was conducted in 25 regions, 166 councils and 357 schools in three phases: (1) August to September 2014; (2) May 2015; and, (3) October 2015.,Children were tested for malaria parasites using rapid diagnostic tests and were interviewed about household information, parents’ education, bed net indicators as well as recent history of fever.,Multilevel mixed effects logistic regression models were fitted to estimate odds ratios of risk factors for malaria infection and for bed net use while adjusting for school effect.,In total, 49,113 children were interviewed and tested for malaria infection.,The overall prevalence of malaria was 21.6%, ranging from < 0.1 to 53% among regions and from 0 to 76.4% among councils.,The malaria prevalence was below 5% in 62 of the 166 councils and above 50% in 18 councils and between 5 and 50% in the other councils.,The variation of malaria prevalence between schools was greatest in regions with a high mean prevalence, while the variation was marked by a few outlying schools in regions with a low mean prevalence.,Overall, 70% of the children reported using mosquito nets, with the highest percentage observed among educated parents (80.7%), low land areas (82.7%) and those living in urban areas (82.2%).,The observed prevalence among school children showed marked variation at regional and sub-regional levels across the country.,Findings of this survey are useful for updating the malaria epidemiological profile and for stratification of malaria transmission by region, council and age groups, which is essential for guiding resource allocation, evaluation and prioritization of malaria interventions.,The online version of this article (10.1186/s12936-018-2601-1) contains supplementary material, which is available to authorized users.

The impact of insecticide treated nets (ITNs) on reducing malaria incidence is shown mainly through data collection from health facilities.,Routine evaluation of long-term epidemiological and entomological dynamics is currently unavailable.,In Kenya, new policies supporting the provision of free ITNs were implemented nationwide in June 2006.,To evaluate the impacts of ITNs on malaria transmission, we conducted monthly surveys in three sentinel sites with different transmission intensities in western Kenya from 2002 to 2010.,Longitudinal samplings of malaria parasite prevalence in asymptomatic school children and vector abundance in randomly selected houses were undertaken monthly from February 2002.,ITN ownership and usage surveys were conducted annually from 2004 to 2010.,Asymptomatic malaria parasite prevalence and vector abundances gradually decreased in all three sites from 2002 to 2006, and parasite prevalence reached its lowest level from late 2006 to early 2007.,The abundance of the major malaria vectors, Anopheles funestus and An. gambiae, increased about 5-10 folds in all study sites after 2007.,However, the resurgence of vectors was highly variable between sites and species.,By 2010, asymptomatic parasite prevalence in Kombewa had resurged to levels recorded in 2004/2005, but the resurgence was smaller in magnitude in the other sites.,Household ITN ownership was at 50-70% in 2009, but the functional and effective bed net coverage in the population was estimated at 40.3%, 49.4% and 28.2% in 2010 in Iguhu, Kombewa, and Marani, respectively.,The resurgence in parasite prevalence and malaria vectors has been observed in two out of three sentinel sites in western Kenya despite a high ownership of ITNs.,The likely factors contributing to malaria resurgence include reduced efficacy of ITNs, insecticide resistance in mosquitoes and lack of proper use of ITNs.,These factors should be targeted to avoid further resurgence of malaria transmission.

Malaria control and elimination strategies are based on levels of transmission that are usually determined by data collected from health facilities.,In endemic areas, asymptomatic Plasmodium infection is thought to represent the majority of infections, though they are not diagnosed nor treated.,Therefore, there might be an underestimation of the malaria reservoir, resulting in inadequate control strategies.,In addition, these untreated asymptomatic Plasmodium infections maintain transmission, making it difficult or impossible to reach malaria elimination goals.,Thus, the aim of this study was to determine the prevalence of asymptomatic Plasmodium infections in southeastern Senegal.,A cross sectional study was conducted among asymptomatic individuals (N = 122) living in the village of Andiel located in Bandafassi, Kédougou, which consisted of about 200 inhabitants during the malaria transmission season in late October 2019.,For each individual without malaria-related symptoms and who consented to participate, a rapid diagnostic test (RDT) was performed in the field.,Results were confirmed in the laboratory with photo-induced electron transfer (PET-PCR).,Malaria prevalence was 70.3% by PET-PCR and 41.8% by RDT.,During the same period, the health post of the area reported 49. 1% test positivity rate by RDT.,The majority of the infected study population, 92.9%, was infected with a single species and 7.1% had two or three species of Plasmodium.,Plasmodium falciparum was predominant and represented 90.2% of the infections, while 6.5% were due to Plasmodium ovale and 3.3% to Plasmodium malariae.,59.4% of children targeted for SMC (zero to ten years old) were infected.,In southeastern Senegal, where the transmission is the highest, malaria control strategies should address asymptomatic Plasmodium infections at the community level.,The results suggest that this area could be eligible for mass drug administration.,Moreover, non-falciparum species could be more common and its prevalence should be determined countrywide.

Plasmodium ovale curtisi and wallikeri are perceived as relapsing malarial parasites.,Contrary to Plasmodium vivax, direct evidence for this hypothesis is scarce.,The aim of this prospective study was to characterize the reappearance patterns of ovale parasites.,P. ovale spp. infected patients were treated with artemether-lumefantrine and followed biweekly for up to 1 year for the detection of reappearing parasitemia.,Molecular analysis of reappearing isolates was performed to identify homologous isolates by genotyping and to define cases of relapse following predefined criteria.,At inclusion, 26 participants were positive for P. ovale curtisi and/or P. ovale wallikeri.,The median duration of follow-up was 35 weeks.,Reappearance of the same P. ovale species was observed in 46% of participants; 61% of P. ovale curtisi and 19% of P. ovale wallikeri infection-free intervals were estimated to end with reappearance by week 32.,Based on the predefined criteria, 23% of participants were identified with 1 or 2 relapses, all induced by P. ovale curtisi.,These findings are in line with the currently accepted relapse theory inasmuch as the reappearance of P. ovale curtisi strains following initial blood clearance was conclusively demonstrated.,Interestingly, no relapse of P. ovale wallikeri was observed.,The formation of hypnozoites and consequential relapse of tertian malaria is a widely accepted theory that lacks, however, confirmation for Plasmodium ovale spp.,This study clinically and molecularly evaluates reappearing P. ovale spp. parasites to provide new evidence.

Soil-transmitted helminths (STH) are the most common parasitic infections in impoverished communities, particularly among children.,Current STH control is through school-based mass drug administration (MDA), which in the Philippines is done twice annually.,As expected, MDA has decreased the intensity and prevalence of STH over time.,As a result, the common Kato Katz (KK) thick smear method of detecting STH is less effective because it lacks sensitivity in low intensity infections, making it difficult to measure the impact of deworming programs.,A cross-sectional study was carried out over a four-week period from October 27, 2014 until November 20, 2014 in Laguna province, the Philippines.,Stool samples were collected from 263 schoolchildren, to determine the prevalence of STH and compare diagnostic accuracy of multiplex quantitative polymerase chain reaction (qPCR) with the KK.,A large discrepancy in the prevalence between the two techniques was noted for the detection of at least one type of STH infection (33.8% by KK vs.,78.3% by qPCR), Ascaris lumbricoides (20.5% by KK vs.,60.8% by qPCR) and Trichuris trichiura (23.6% by KK vs.,38.8% by qPCR).,Considering the combined results of both methods, the prevalence of at least one type of helminth infection, A. lumbricoides, and T. trichiura were 83.3%, 67.7%, and 53.6%, respectively.,Sensitivity of the qPCR for detecting at least one type of STH infection, A. lumbricoides, and T. trichiura were 94.1%, 89.9%, and 72.3% respectively; whereas KK sensitivity was 40.6%, 30.3%, and 44.0%, respectively.,The qPCR method also detected infections with Ancylostoma spp.,(4.6%), Necator americanus (2.3%), and Strongyloides stercoralis (0.8%) that were missed by KK.,qPCR may provide new and important diagnostic information to improve assessment of the effectiveness and impact of integrated control strategies particularly in areas where large-scale STH control has led to low prevalence and/or intensity of infection.

Hookworm infections are an important cause of (severe) anemia and iron deficiency in children in the tropics.,Type of hookworm species (Ancylostoma duodenale or Necator americanus) and infection load are considered associated with disease burden, although these parameters are rarely assessed due to limitations of currently used diagnostic methods.,Using multiplex real-time PCR, we evaluated hookworm species-specific prevalence, infection load and their contribution towards severe anemia and iron deficiency in pre-school children in Malawi.,A. duodenale and N. americanus DNA loads were determined in 830 fecal samples of pre-school children participating in a case control study investigating severe anemia.,Using multiplex real-time PCR, hookworm infections were found in 34.1% of the severely anemic cases and in 27.0% of the non-severely anemic controls (p<0.05) whereas a 5.6% hookworm prevalence was detected by microscopy.,Prevalence of A. duodenale and N. americanus was 26.1% and 4.9% respectively.,Moderate and high load A. duodenale infections were positively associated with severe anemia (adjusted odds ratio: 2.49 (95%CI 1.16-5.33) and 9.04 (95%CI 2.52-32.47) respectively).,Iron deficiency (assessed through bone marrow examination) was positively associated with intensity of A. duodenale infection (adjusted odds ratio: 3.63 (95%CI 1.18-11.20); 16.98 (95%CI 3.88-74.35) and 44.91 (95%CI 5.23-385.77) for low, moderate and high load respectively).,This is the first report assessing the association of hookworm load and species differentiation with severe anemia and bone marrow iron deficiency.,By revealing a much higher than expected prevalence of A. duodenale and its significant and load-dependent association with severe anemia and iron deficiency in pre-school children in Malawi, we demonstrated the need for quantitative and species-specific screening of hookworm infections.,Multiplex real-time PCR is a powerful diagnostic tool for public health research to combat (severe) anemia and iron deficiency in children living in resource poor settings.

•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.

The Kato-Katz thick smear (Kato-Katz) is the diagnostic method recommended for monitoring large-scale treatment programs implemented for the control of soil-transmitted helminths (STH) in public health, yet it is difficult to standardize.,A promising alternative is the McMaster egg counting method (McMaster), commonly used in veterinary parasitology, but rarely so for the detection of STH in human stool.,The Kato-Katz and McMaster methods were compared for the detection of STH in 1,543 subjects resident in five countries across Africa, Asia and South America.,The consistency of the performance of both methods in different trials, the validity of the fixed multiplication factor employed in the Kato-Katz method and the accuracy of these methods for estimating ‘true’ drug efficacies were assessed.,The Kato-Katz method detected significantly more Ascaris lumbricoides infections (88.1% vs.,75.6%, p<0.001), whereas the difference in sensitivity between the two methods was non-significant for hookworm (78.3% vs.,72.4%) and Trichuris trichiura (82.6% vs.,80.3%).,The sensitivity of the methods varied significantly across trials and magnitude of fecal egg counts (FEC).,Quantitative comparison revealed a significant correlation (Rs >0.32) in FEC between both methods, and indicated no significant difference in FEC, except for A. lumbricoides, where the Kato-Katz resulted in significantly higher FEC (14,197 eggs per gram of stool (EPG) vs.,5,982 EPG).,For the Kato-Katz, the fixed multiplication factor resulted in significantly higher FEC than the multiplication factor adjusted for mass of feces examined for A. lumbricoides (16,538 EPG vs.,15,396 EPG) and T. trichiura (1,490 EPG vs.,1,363 EPG), but not for hookworm.,The McMaster provided more accurate efficacy results (absolute difference to ‘true’ drug efficacy: 1.7% vs.,4.5%).,The McMaster is an alternative method for monitoring large-scale treatment programs.,It is a robust (accurate multiplication factor) and accurate (reliable efficacy results) method, which can be easily standardized.

Trichinellosis is a meat-borne zoonotic disease caused by parasites of the genus Trichinella.,To date, 12 taxa have been described.,The identification of Trichinella species is crucial in order to identify the possible source of infection, the geographical origin of the parasite and to assess risk of infection for domestic pigs and humans.,Specific identification of the etiological agent is not always feasible using direct methods since the source of infection can be untraceable.,The aim of this study was to develop a diagnostic tool to infer the causative Trichinella species using western blot patterns of sera derived from infected animal and human hosts.,Sera from mice experimentally infected with Trichinella spiralis, Trichinella britovi, Trichinella pseudospiralis and Trichinella papuae were tested by western blot using homologous and heterologous crude worm extracts (CWE) and a highly sensitive detection system based on chemiluminescence.,In addition, sera from pigs experimentally infected with T. spiralis, T. britovi and T. pseudospiralis and from patients with confirmed T. spiralis, T. britovi and T. pseudospiralis infections, were also included.,Sera from mice infected with one Trichinella species reacted with CWE proteins from all four investigated species.,Likewise, sera derived from pigs and humans infected with one Trichinella species reacted with CWE proteins from all the three investigated species.,Using T. spiralis CWE, sera from T. pseudospiralis-infected hosts yielded a characteristic pattern of reactivity using Wb, which differed to that produced by T. spiralis/T. britovi- or T. papuae-infected host sera.,The present study suggests that western blot using T. spiralis CWE may be a useful tool to distinguish Trichinella infections caused by T. pseudospiralis from those caused by T. spiralis or T. britovi.,This method may support epidemiological investigations, particularly when the source of infection is not traceable.,The online version of this article (10.1186/s13071-018-3244-3) contains supplementary material, which is available to authorized users.

Natural killer (NK) cells are classic innate immune cells that play roles in many types of infectious diseases.,NK cells possess many kinds of TLRs that allow them to sense and respond to invading pathogens.,Our previous study found that NK cells could modulate the immune response induced by Schistosoma japonicum (S. japonicum) in C57BL/6 mice.,In the present study, the role of TLRs in the progress of S. japonicum infection was investigated.,Results showed that the expression of TLR3 on NK cells increased significantly after S. japonicum infection by using RT-PCR and FACS (P < 0.05).,TLR3 agonist (Poly I:C) increased IFN-γ and IL-4 levels in the supernatant of cultured splenocytes and induced a higher percentage of IFN-γ- and IL-4-secreting NK cells from infected mouse splenocytes (P < 0.05).,Not only the percentages of MHC II-, CD69-, and NKG2A/C/E-expressing cells but also the percentages of IL-4-, IL-5-, and IL-17-producing cells in TLR3+ NK cells increased significantly after infection (P < 0.05).,Moreover, the expression of NKG2A/C/E, NKG2D, MHC II, and CD69 on the surface of splenic NK cells was changed in S. japonicum-infected TLR3−/− (TLR3 KO mice, P < 0.05); the abilities of NK cells in IL-4, IL-5, and IL-17 secretion were decreased too (P < 0.05).,These results indicate that TLR3 is the primary molecule which modulates the activation and function of NK cells during the course of S. japonicum infection in C57BL/6 mice.

Cerebral malaria (CM) is a severe neurological complication of Plasmodium falciparum infection.,A number of pathological findings have been correlated with pediatric CM including sequestration, platelet accumulation, petechial haemorrhage and retinopathy.,However, the molecular mechanisms leading to death in CM are not yet fully understood.,A shotgun plasma proteomic study was conducted using samples form 52 Gambian children with CM admitted to hospital.,Based on clinical outcome, children were assigned to two groups: reversible and fatal CM.,Label-free liquid chromatography-tandem mass spectrometry was used to identify and compare plasma proteins that were differentially regulated in children who recovered from CM and those who died.,Candidate biomarkers were validated using enzyme immunoassays.,The plasma proteomic signature of children with CM identified 266 proteins differentially regulated in children with fatal CM.,Proteins from the coagulation cascade were consistently decreased in fatal CM, whereas the plasma proteomic signature associated with fatal CM underscored the importance of endothelial activation, tissue damage, inflammation, haemolysis and glucose metabolism.,The concentration of circulating proteasomes or PSMB9 in plasma was not significantly different in fatal CM when compared with survivors.,Plasma PSMB9 concentration was higher in patients who presented with seizures and was significantly correlated with the number of seizures observed in patients with CM during admission.,The results indicate that increased tissue damage and hypercoagulability may play an important role in fatal CM.,The diagnostic value of this molecular signature to identify children at high risk of dying to optimize patient referral practices should be validated prospectively.,The online version of this article (10.1186/s12936-018-2487-y) contains supplementary material, which is available to authorized users.

Objectives To determine which travellers with malaria are at greatest risk of dying, highlighting factors which can be used to target health messages to travellers.,Design Observational study based on 20 years of UK national data.,Setting National register of malaria cases.,Participants 25 054 patients notified with Plasmodium falciparum malaria, of whom 184 died, between 1987 and 2006.,Main outcome measures Comparison between those with falciparum malaria who died and non-fatal cases, including age, reason for travel, country of birth, time of year diagnosed, malaria prophylaxis used.,Results Mortality increased steadily with age, with a case fatality of 25/548 (4.6%) in people aged >65 years, adjusted odds ratio 10.68 (95% confidence interval 6.4 to 17.8), P<0.001 compared with 18-35 year olds.,There were no deaths in the ≤5 year age group.,Case fatality was 3.0% (81/2740 cases) in tourists compared with 0.32% (26/8077) in travellers visiting friends and relatives (adjusted odds ratio 8.2 (5.1 to 13.3), P<0.001).,Those born in African countries with endemic malaria had a case fatality of 0.4% (36/8937) compared with 2.4% (142/5849) in others (adjusted odds ratio 4.6 (3.1 to 9.9), P<0.001).,Case fatality was particularly high from the Gambia.,There was an inverse correlation in mortality between region of presentation and number of cases seen in the region (R2=0.72, P<0.001).,Most delay in fatal cases was in seeking care.,Conclusions Most travellers acquiring malaria are of African heritage visiting friends and relatives.,In contrast the risks of dying from malaria once acquired are highest in the elderly, tourists, and those presenting in areas in which malaria is seldom seen.,Doctors often do not think of these as high risk groups for malaria; for this reason they are important groups to target in pre-travel advice.

Understanding the targets and mechanisms of human immunity to malaria caused by Plasmodium falciparum is crucial for advancing effective vaccines and developing tools for measuring immunity and exposure in populations.,Acquired immunity to malaria predominantly targets the blood stage of infection when merozoites of Plasmodium spp. infect erythrocytes and replicate within them.,During the intra-erythrocytic development of P. falciparum, numerous parasite-derived antigens are expressed on the surface of infected erythrocytes (IEs).,These antigens enable P. falciparum-IEs to adhere in the vasculature and accumulate in multiple organs, which is a key process in the pathogenesis of disease.,IE surface antigens, often referred to as variant surface antigens, are important targets of acquired protective immunity and include PfEMP1, RIFIN, STEVOR and SURFIN.,These antigens are highly polymorphic and encoded by multigene families, which generate substantial antigenic diversity to mediate immune evasion.,The most important immune target appears to be PfEMP1, which is a major ligand for vascular adhesion and sequestration of IEs.,Studies are beginning to identify specific variants of PfEMP1 linked to disease pathogenesis that may be suitable for vaccine development, but overcoming antigenic diversity in PfEMP1 remains a major challenge.,Much less is known about other surface antigens, or antigens on the surface of gametocyte-IEs, the effector mechanisms that mediate immunity, and how immunity is acquired and maintained over time; these are important topics for future research.,The online version of this article (doi:10.1007/s00018-014-1614-3) contains supplementary material, which is available to authorized users.

In eukaryotic organisms, gene expression is regulated at multiple levels during the processes of transcription and translation.,The absence of a tight regulatory network for transcription in the human malaria parasite suggests that gene expression may largely be controlled at post-transcriptional and translational levels.,In this study, we compare steady-state mRNA and polysome-associated mRNA levels of Plasmodium falciparum at different time points during its asexual cell cycle.,For more than 30% of its genes, we observe a delay in peak transcript abundance in the polysomal fraction as compared to the steady-state mRNA fraction, suggestive of strong translational control.,Our data show that key regulatory mechanisms could include inhibitory activity of upstream open reading frames and translational repression of the major virulence gene family by intronic transcripts.,In addition, we observe polysomal mRNA-specific alternative splicing events and widespread transcription of non-coding transcripts.,These different layers of translational regulation are likely to contribute to a complex network that controls gene expression in this eukaryotic pathogen.,Disrupting the mechanisms involved in such translational control could provide novel anti-malarial strategies.

Malaria is one of the deadliest infectious diseases to affect humans, causing over 200 million cases and hundreds of thousands of deaths annually.,Its fatal symptoms occur when parasites cause infected human red blood cells to stick to human tissue surfaces, blocking blood flow and causing inflammation.,This stickiness is caused by parasite PfEMP1 proteins, which interact with different human receptors, such as ICAM-1.,In this paper, we demonstrate how PfEMP1 proteins bind to ICAM-1.,We find that this can happen in 2 different but related ways, perhaps influencing which additional receptors PfEMP1 can bind.,We show how the parasite can adapt to allow it to stick tightly, while reducing the chance that it is detected and destroyed.,A major determinant of pathogenicity in malaria caused by Plasmodium falciparum is the adhesion of parasite-infected erythrocytes to the vasculature or tissues of infected individuals.,This occludes blood flow, leads to inflammation, and increases parasitemia by reducing spleen-mediated clearance of the parasite.,This adhesion is mediated by PfEMP1, a multivariant family of around 60 proteins per parasite genome which interact with specific host receptors.,One of the most common of these receptors is intracellular adhesion molecule-1 (ICAM-1), which is bound by 2 distinct groups of PfEMP1, A-type and B or C (BC)-type.,Here, we present the structure of a domain from a B-type PfEMP1 bound to ICAM-1, revealing a complex binding site.,Comparison with the existing structure of an A-type PfEMP1 bound to ICAM-1 shows that the 2 complexes share a globally similar architecture.,However, while the A-type PfEMP1 bind ICAM-1 through a highly conserved binding surface, the BC-type PfEMP1 use a binding site that is more diverse in sequence, similar to how PfEMP1 interact with other human receptors.,We also show that A- and BC-type PfEMP1 present ICAM-1 at different angles, perhaps influencing the ability of neighboring PfEMP1 domains to bind additional receptors.,This illustrates the deep diversity of the PfEMP1 and demonstrates how variations in a single domain architecture can modulate binding to a specific ligand to control function and facilitate immune evasion.

The development of immunoregulatory networks is important to prevent disease.,However, these same networks allow pathogens to persist and reduce vaccine efficacy.,Here, we identify type I interferons (IFNs) as important regulators in developing anti-parasitic immunity in healthy volunteers infected for the first time with Plasmodium falciparum.,Type I IFNs suppressed innate immune cell function and parasitic-specific CD4+ T cell IFNγ production, and they promoted the development of parasitic-specific IL-10-producing Th1 (Tr1) cells.,Type I IFN-dependent, parasite-specific IL-10 production was also observed in P. falciparum malaria patients in the field following chemoprophylaxis.,Parasite-induced IL-10 suppressed inflammatory cytokine production, and IL-10 levels after drug treatment were positively associated with parasite burdens before anti-parasitic drug administration.,These findings have important implications for understanding the development of host immune responses following blood-stage P. falciparum infection, and they identify type I IFNs and related signaling pathways as potential targets for therapies or vaccine efficacy improvement.

Echinococcosis has led to considerable social and economic losses in China, particularly in the endemic communities of the eastern Tibetan Plateau.,In China, human cases of Echinococcus granulosus (sensu stricto), E. canadensis and E. multilocularis infections have been described, but no E. ortleppi (G5) infections in humans or animals have been reported.,A case of E. ortleppi infection in a human from Guangxi, which is a non-endemic echinococcosis area in China, is described.,A 17 × 12 × 20 cm (diameter) cyst was observed in the liver of the patient, and Echinococcus larvae were collected from the cyst.,A morphological examination indicated that the larvae were E. ortleppi, and amplification and analysis of the nicotinamide adenine dinucleotide hydrogenase dehydrogenase subunit 1 (nad1) and cytochrome c oxidase subunit 1 (cox1) genes showed that the larvae had 99-100% homology with the corresponding E. ortleppi sequences on GenBank.,To our knowledge, this report describes the first identification of a human E. ortleppi infection in China.,Our data broaden the geographical distribution of this rarely reported species of Echinococcus.,The online version of this article (10.1186/s13071-019-3653-y) contains supplementary material, which is available to authorized users.

This study was conducted to determine the prevalence of cystic echinococcosis (CE) in small ruminants and humans in Addis Ababa, central Ethiopia.,A cross-sectional study involving systematic random sampling was conducted to estimate the prevalence of CE in 512 small ruminants (262 sheep and 250 goats) slaughtered at Addis Ababa Abattoir Enterprise between October 2011 and March 2012.,Hydatid cysts were identified macroscopically during postmortem examination and their fertility and viability were determined.,CE was observed in 21 (8.02%) sheep and 17 (6.80%) goats.,In sheep 13 (4.96%) of the lungs, 10 (3.81%) livers and 1 (0.381%) heart were found to be infected with hydatid cysts.,Involvement of lung and liver in goats was found to be 10 (4.0%) and 8 (3.2%) respectively, with no cysts recorded in the heart.,Of the total of 77 and 47 cysts encountered in sheep and goats, 33 (42.85%) and 15 (31.91%) respectively were fertile.,Viability of protoscoleces from fertile cysts in sheep (29 [87.87%]) was higher than in goats (6 [40.0%]).,For humans, retrospective analysis covering five years of case reports at two major hospitals in Addis Ababa between January 2008 and December 2012 showed that of the total of 25 840 patients admitted for ultrasound examination, 27 CE cases were registered, a prevalence of 0.1% and mean annual incidence rate of approximately 0.18 cases per 100 000 population.,Liver was the major organ affected in humans (81.5% in affected patients) followed by spleen (11.1%) and kidney (7.4%).,Logistic regression analysis showed that prevalence of CE varied significantly in relation to host age in the small ruminants (OR = 3.93, P < 0.05) as well as in humans (95% CI, R = 4.8).,This epidemiological study confirms the importance of CE in small ruminants and humans in central Ethiopia, emphasising the need for integrated approaches to controlling this neglected preventable disease.

Antigenic variation in malaria was discovered in Plasmodium knowlesi studies involving longitudinal infections of rhesus macaques (M. mulatta).,The variant proteins, known as the P. knowlesi Schizont Infected Cell Agglutination (SICA) antigens and the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) antigens, expressed by the SICAvar and var multigene families, respectively, have been studied for over 30 years.,Expression of the SICA antigens in P. knowlesi requires a splenic component, and specific antibodies are necessary for variant antigen switch events in vivo.,Outstanding questions revolve around the role of the spleen and the mechanisms by which the expression of these variant antigen families are regulated.,Importantly, the longitudinal dynamics and molecular mechanisms that govern variant antigen expression can be studied with P. knowlesi infection of its mammalian and vector hosts.,Synchronous infections can be initiated with established clones and studied at multi-omic levels, with the benefit of computational tools from systems biology that permit the integration of datasets and the design of explanatory, predictive mathematical models.,Here we provide an historical account of this topic, while highlighting the potential for maximizing the use of P. knowlesi - macaque model systems and summarizing exciting new progress in this area of research.

Relapse may have evolved in malaria as a mechanism to avoid suppression by more virulent species in mixed infections, thereby increasing transmission opportunities.,Later evolution of long latency in Plasmodium vivax was a necessary adaptation as early hominins moved to colder areas with shorter mosquito breeding seasons.,Genetic diversity was maintained through heterologous hypnozoite activation.

The Greater Mekong Subregion is aiming to achieve regional malaria elimination by 2030.,Though a shift in malaria parasite species predominance by Plasmodium vivax has been recently documented, the transmission of the two minor Plasmodium species, Plasmodium malariae and Plasmodium ovale spp., is poorly characterized in the region.,This study aims to determine the prevalence of these minor species in the China-Myanmar border area and their genetic diversity.,Epidemiology study was conducted during passive case detection in hospitals and clinics in Myanmar and four counties in China along the China-Myanmar border.,Cross-sectional surveys were conducted in villages and camps for internally displaced persons to determine the prevalence of malaria infections.,Malaria infections were diagnosed initially by microscopy and later in the laboratory using nested PCR for the SSU rRNA genes.,Plasmodium malariae and P. ovale infections were confirmed by sequencing the PCR products.,The P. ovale subtypes were determined by sequencing the Pocytb, Pocox1 and Pog3p genes.,Parasite populations were evaluated by PCR amplification and sequencing of the MSP-1 genes.,Antifolate sensitivity was assessed by sequencing the dhfr-ts and dhps genes from the P. malariae and P. ovale isolates.,Analysis of 2701 blood samples collected from the China-Myanmar border by nested PCR targeting the parasite SSU rRNA genes identified 561 malaria cases, including 161 Plasmodium falciparum, 327 P. vivax, 66 P. falciparum/P. vivax mixed infections, 4 P. malariae and 3 P. ovale spp.,P. vivax and P. falciparum accounted for >60 and ~30% of all malaria cases, respectively.,In comparison, the prevalence of P. malariae and P. ovale spp. was very low and only made up ~1% of all PCR-positive cases.,Nevertheless, these two species were often misidentified as P. vivax infections or completely missed by microscopy even among symptomatic patients.,Phylogenetic analysis of the SSU rRNA, Pocytb, Pocox1 and Pog3p genes confirmed that the three P. ovale spp. isolates belonged to the subtype P. ovale curtisi.,Low-level genetic diversity was detected in the MSP-1, dhfr and dhps genes of these minor parasite species, potentially stemming from the low prevalence of these parasites preventing their mixing.,Whereas most of the dhfr and dhps positions equivalent to those conferring antifolate resistance in P. falciparum and P. vivax were wild type, a new mutation S113C corresponding to the S108 position in pfdhfr was identified in two P. ovale curtisi isolates.,The four human malaria parasite species all occurred sympatrically at the China-Myanmar border.,While P. vivax has become the predominant species, the two minor parasite species also occurred at very low prevalence but were often misidentified or missed by conventional microscopy.,These minor parasite species displayed low levels of polymorphisms in the msp-1, dhfr and dhps genes.,The online version of this article (doi:10.1186/s12936-016-1605-y) contains supplementary material, which is available to authorized users.

In Ethiopia Plasmodium falciparum and Plasmodium vivax are the dominant species accounting for roughly 60 and 40% of malaria cases, respectively.,Recently a major shift from P. falciparum to P. vivax has been observed in various parts of the country but the epidemiology of the other human malaria species, Plasmodium ovale spp. and Plasmodium malariae remains poorly understood.,The aim of this study was to assess P. ovale curtisi and wallikeri infection in north-west Ethiopia by using microscopy and nested PCR.,A health institution-based survey using non-probability sampling techniques was conducted at Maksegnet, Enfranze and Kola Diba health centres and Metema hospital in North Gondar.,Three-hundred patients with signs and symptoms consistent with malaria were included in this study and capillary blood was collected for microscopic examination and molecular analysis of Plasmodium species.,Samples were collected on Whatman 903 filter papers, stored in small plastic bags with desiccant and transported to Vienna (Austria) for molecular analysis.,Data from study participants were entered and analysed by SPSS 20 software.,Out of 300 study participants (167 males and 133 females), 184 samples were classified positive for malaria (133 P. falciparum and 51 P. vivax) by microscopy.,By species-specific PCR 233 Plasmodium spp (95% CI: 72.6-82) were detected and the majority 155 (66.5%, 95% CI: 60.2-72.3) were P. falciparum followed by P. vivax 69 (29.6%, 95% CI; 24.1-35.8) and 9 (3.9%, 95% CI: 2-7.2) samples were positive for P. ovale.,Seven of P. ovale parasites were confirmed as P. ovale wallikeri and two were confirmed as P. ovale curtisi.,None of the samples tested positive for P. malariae.,During microscopic examination there were high (16.3%) false negative reports and all mixed infections and P. ovale cases were missed or misclassified.,This study indicates that P. ovale malaria is under-reported in Ethiopia and provides the first known evidence of the sympatric distribution of indigenous P. ovale wallikeri and P. ovale curtisi in Ethiopia.,Therefore, further studies assessing the prevalence of the rare species P. ovale and P. malariae are urgently needed to better understand the species distribution and to adapt malaria control strategies.

The host immunological response is a key factor determining the pathogenesis of cutaneous leishmaniasis.,It is known that a Th1 cellular response is associated with infection control and that antigen-specific memory T cells are necessary for the development of a rapid and strong protective cellular response.,The present manuscript reports the analysis of the functional and phenotypic profiles of antigen-specific CD4+ and CD8+ T cells from patients cured of cutaneous leishmaniasis (CL), patients with an active process of cutaneous leishmaniasis, asymptomatic individuals with a positive Montenegro test and healthy donors (HD).,Peripheral blood mononuclear cells (PBMCs) from the patients exhibited a lymphoproliferative capacity after stimulation with total soluble protein from either Leishmania panamensis (SLpA) or Leishmania infantum (SLiA) or with a recombinant paraflagellar rod protein-1 (rPFR1).,Higher frequencies of antigen-specific TNAIVE cells, mainly following stimulation with rPFR1, were observed in asymptomatic and cured patients than in patients with active cutaneous leishmaniasis, while T cells from patients with active cutaneous leishmaniasis showed a higher percentage of effector memory T cells (TEM for CD4+ T cells and TEMRA for CD8+ T cells).,The amount of antigen-specific CD57+/CD8+ TEMRA cells in patients with active cutaneous leishmaniasis was higher than that in cured patients and asymptomatic subjects.,Regarding functionality, a more robust multifunctional CD8+ T cell response was detected in cured patients than in those with active cutaneous leishmaniasis.,Moreover, cured patients showed a significant increase in the frequency of cells expressing a Th1-type cytotoxic production profile (IFN-γ+/granzyme-B/+perforin+).,Patients with an active leishmaniosis process had a significantly higher frequency of CD8+ T cells expressing the inhibitory CD160 and 2B4 receptors than did cured patients.,The expression profile observed in cured patients could be indicative of an imbalance toward a CD8+ Th1 response, which could be associated with infection control; consequently, the determination of this profile could be a useful tool for facilitating the clinical follow-up of patients with cutaneous leishmaniasis.,The results also suggest a possible exhaustion process of CD8+ T cells associated with the evolution of Leishmania infection.

Leishmania is transmitted by female sand flies and deposited together with saliva, which contains a vast repertoire of pharmacologically active molecules that contribute to the establishment of the infection.,The exposure to vector saliva induces an immune response against its components that can be used as a marker of exposure to the vector.,Performing large-scale serological studies to detect vector exposure has been limited by the difficulty in obtaining sand fly saliva.,Here, we validate the use of two sand fly salivary recombinant proteins as markers for vector exposure.,ELISA was used to screen human sera, collected in an area endemic for visceral leishmaniasis, against the salivary gland sonicate (SGS) or two recombinant proteins (rLJM11 and rLJM17) from Lutzomyia longipalpis saliva.,Antibody levels before and after SGS seroconversion (n = 26) were compared using the Wilcoxon signed rank paired test.,Human sera from an area endemic for VL which recognize Lu. longipalpis saliva in ELISA also recognize a combination of rLJM17 and rLJM11.,We then extended the analysis to include 40 sera from individuals who were seropositive and 40 seronegative to Lu. longipalpis SGS.,Each recombinant protein was able to detect anti-saliva seroconversion, whereas the two proteins combined increased the detection significantly.,Additionally, we evaluated the specificity of the anti-Lu. longipalpis response by testing 40 sera positive to Lutzomyia intermedia SGS, and very limited (2/40) cross-reactivity was observed.,Receiver-operator characteristics (ROC) curve analysis was used to identify the effectiveness of these proteins for the prediction of anti-SGS positivity.,These ROC curves evidenced the superior performance of rLJM17+rLJM11.,Predicted threshold levels were confirmed for rLJM17+rLJM11 using a large panel of 1,077 serum samples.,Our results show the possibility of substituting Lu. longipalpis SGS for two recombinant proteins, LJM17 and LJM11, in order to probe for vector exposure in individuals residing in endemic areas.

Malaria is heterogeneously distributed across landscapes.,Human population movement (HPM) could link sub-regions with varying levels of transmission, leading to the persistence of disease even in very low transmission settings.,Malaria along the Thai-Myanmar border has been decreasing, but remains heterogeneous.,This study aimed to measure HPM, associated predictors of travel, and HPM correlates of self-reported malaria among people living within malaria hotspots.,526 individuals from 279 households in two malaria hotspot areas were included in a prospective observational study.,A baseline cross-sectional study was conducted at the beginning, recording both individual- and household-level characteristics.,Individual movement and travel patterns were repeatedly observed over one dry season month (March) and one wet season month (May).,Descriptive statistics, random effects logistic regressions, and logistic regressions were used to describe and determine associations between HPM patterns, individual-, household-factors, and self-reported malaria.,Trips were more common in the dry season.,Malaria risk was related to the number of days doing outdoor activities in the dry season, especially trips to Myanmar, to forest areas, and overnight trips.,Trips to visit forest areas were more common among participants aged 20-39, males, individuals with low income, low education, and especially among individuals with forest-related occupations.,Overnight trips were more common among males, and individual with forest-related occupations.,Forty-five participants reported having confirmed malaria infection within the last year.,The main place of malaria blood examination and treatment was malaria post and malaria clinic, with participants usually waiting for 2-3 days from onset fever to seeking diagnosis.,Individuals using bed nets, living in houses with elevated floors, and houses that received indoor residual spraying in the last year were less likely to report malaria infection.,An understanding of HPM and concurrent malaria dynamics is important for consideration of targeted public health interventions.,Furthermore, diagnosis and treatment centres must be capable of quickly diagnosing and treating infections regardless of HPM.,Coverage of diagnosis and treatment centres should be broad, maintained in areas bordering malaria hotspots, and available to all febrile individuals.,The online version of this article (10.1186/s12936-019-2704-3) contains supplementary material, which is available to authorized users.

Cross-border malaria transmission is an important problem for national malaria control programmes.,The epidemiology of cross-border malaria is further complicated in areas where Plasmodium falciparum and Plasmodium vivax are both endemic.,By combining passive case detection data with entomological data, a transmission scenario on the northwestern Thai-Myanmar border where P. falciparum is likely driven by importation was described, whereas P. vivax is also locally transmitted.,This study highlights the differences in the level of control required to eliminate P. falciparum and P. vivax from the same region.,Malaria case data were collected from malaria clinics in Suan Oi village, Tak Province, Thailand between 2011 and 2014.,Infections were diagnosed by light microscopy.,Demographic data, including migrant status, were correlated with concomitantly collected entomology data from 1330 mosquito trap nights using logistic regression.,Malaria infection in the captured mosquitoes was detected by ELISA.,Recent migrants were almost four times more likely to be infected with P. falciparum compared with Thai patients (OR 3.84, p < 0.001) and cases were significantly associated with seasonal migration.,However, P. falciparum infection was not associated with the Anopheles mosquito capture rates, suggesting predominantly imported infections.,In contrast, recent migrants were equally likely to present with P. vivax as mid-term migrants.,Both migrant groups were twice as likely to be infected with P. vivax in comparison to the resident Thai population (OR 1.96, p < 0.001 and OR 1.94, p < 0.001, respectively).,Plasmodium vivax cases were strongly correlated with age and local capture rates of two major vector species Anopheles minimus and Anopheles maculatus (OR 1.23, p = 0.020 and OR 1.33, p = 0.046, respectively), suggesting that a high level of local transmission might be causing these infections.,On the Thai-Myanmar border, P. falciparum infections occur mostly in the recent migrant population with a seasonality reflecting that of agricultural activity, rather than that of the local mosquito population.,This suggests that P. falciparum was mostly imported.,In contrast, P. vivax cases were significantly associated with mosquito capture rates and less with migrant status, indicating local transmission.,This highlights the different timelines and requirements for P. falciparum and P. vivax elimination in the same region and underlines the importance of multinational, cross-border malaria control.,The online version of this article (doi:10.1186/s12936-017-1900-2) contains supplementary material, which is available to authorized users.

In order to prepare the field site for future interventions, the prevalence of asymptomatic Plasmodium falciparum infection was evaluated in a cohort of children living in Brazzaville.,Plasmodium falciparum merozoite surface protein 2 gene (msp2) was used to characterize the genetic diversity and the multiplicity of infection.,The prevalence of mutant P. falciparum chloroquine resistance transporter (pfcrt) allele in isolates was also determined.,Between April and June 2010, 313 children below 10 years of age enrolled in the cohort for malaria surveillance were screened for P. falciparum infection using microscopy and polymerase chain reaction (PCR).,The children were selected on the basis of being asymptomatic.,Plasmodium falciparum msp2 gene was genotyped by allele-specific nested PCR and the pfcrt K76T mutation was detected using nested PCR followed by restriction endonuclease digestion.,The prevalence of asymptomatic P. falciparum infections was 8.6% and 16% by microscopy and by PCR respectively.,Allele typing of the msp2 gene detected 55% and 45% of 3D7 and FC27 allelic families respectively.,The overall multiplicity of infections (MOI) was 1.3.,A positive correlation between parasite density and multiplicity of infection was found.,The prevalence of the mutant pfcrt allele (T76) in the isolates was 92%.,This is the first molecular characterization of P. falciparum field isolates in Congolese children, four years after changing the malaria treatment policy from chloroquine (CQ) to artemisinin-based combination therapy (ACT).,The low prevalence of asymptomatic infections and MOI is discussed in the light of similar studies conducted in Central Africa.

Many malaria-related studies depend on infected red blood cells (iRBCs) as fundamental material; however, infected blood samples from human or animal models include leukocytes (white blood cells or WBCs), especially difficult to separate from iRBCs in cases involving Plasmodium vivax.,These host WBCs are a source of contamination in biology, immunology and molecular biology studies, requiring their removal.,Non-woven fabric (NWF) has the ability to adsorb leukocytes and is already used as filtration material to deplete WBCs for blood transfusion and surgery.,The present study describes the development and evaluation of a prototype NWF filter designed for purifying iRBCs from malaria-infected blood.,Blood samples of P. vivax patients were processed separately by NWF filter and CF11 column methods.,WBCs and RBCs were counted, parasite density, morphology and developing stage was checked by microscopy, and compared before and after treatment.,The viability of filtrated P. vivax parasites was examined by in vitro short-term cultivation.,A total of 15 P. vivax-infected blood samples were treated by both NWF filter and CF11 methods.,The WBC removal rate of the NWF filter method was 99.03%, significantly higher than the CF11 methods (98.41%, P < 0.01).,The RBC recovery rate of the NWF filter method was 95.48%, also significantly higher than the CF11 method (87.05%, P < 0.01).,Fourteen in vitro short-term culture results showed that after filter treatment, P. vivax parasite could develop as normal as CF11 method, and no obvious density, developing stage difference were fund between two methods.,NWF filter filtration removed most leukocytes from malaria-infected blood, and the recovery rate of RBCs was higher than with CF11 column method.,Filtrated P. vivax parasites were morphologically normal, viable, and suitable for short-term in vitro culture.,NWF filter filtration is simple, fast and robust, and is ideal for purification of malaria-infected blood.

Quantification of malaria heterogeneity is very challenging, partly because of the underlying characteristics of mosquitoes and also because malaria is an environmentally driven disease.,Furthermore, in order to assess the spatial and seasonal variability in malaria transmission, vector data need to be collected repeatedly over time (at fixed geographical locations).,Measurements collected at locations close to each other and over time tend to be correlated because of common exposures such as environmental or climatic conditions.,Non- spatial statistical methods, when applied to analyze such data, may lead to biased estimates.,We developed rigorous methods for analyzing sparse and spatially correlated data.,We applied Bayesian variable selection to identify the most important predictors as well as the elapsing time between climate suitability and changes in entomological indices.,Bayesian geostatistical zero-inflated binomial and negative binomial models including harmonic seasonal terms, temporal trends and climatic remotely sensed proxies were applied to assess spatio-temporal variation of sporozoite rate and mosquito density in the study area.,Bayesian variable selection was employed to determine the most important climatic predictors and elapsing (lag) time between climatic suitability and malaria transmission.,Bayesian kriging was used to predict mosquito density and sporozoite rate at unsampled locations.,These estimates were converted to covariate and season-adjusted maps of entomological inoculation rates.,Models were fitted using Markov chain Monte Carlo simulation.,The results show that Anophele. gambiae is the most predominant vector (79.29%) and is more rain-dependant than its sibling Anophele. funestus (20.71%).,Variable selection suggests that the two species react differently to different climatic conditions.,Prediction maps of entomological inoculation rate (EIR) depict a strong spatial and temporal heterogeneity in malaria transmission risk despite the relatively small geographical extend of the study area.,Malaria transmission is very heterogeneous over the study area.,The EIR maps clearly depict a strong spatial and temporal heterogeneity despite the relatively small geographical extend of the study area.,Model based estimates of transmission can be used to identify high transmission areas in order to prioritise interventions and support research in malaria epidemiology.,The online version of this article (doi:10.1186/s13071-015-0679-7) contains supplementary material, which is available to authorized users.

Over a decade ago, the Roll Back Malaria Partnership was launched, and since then there has been unprecedented investment in malaria control.,We examined the change in malaria transmission intensity during the period 2000-10 in Africa.,We assembled a geocoded and community Plasmodium falciparum parasite rate standardised to the age group 2-10 years (PfPR2-10) database from across 49 endemic countries and territories in Africa from surveys undertaken since 1980.,The data were used within a Bayesian space-time geostatistical framework to predict PfPR2-10 in 2000 and 2010 at a 1 × 1 km spatial resolution.,Population distribution maps at the same spatial resolution were used to compute populations at risk by endemicity class and estimate population-adjusted PfPR2-10 (PAPfPR2-10) for each of the 44 countries for which predictions were possible for each year.,Between 2000 and 2010, the population in hyperendemic (>50% to 75% PfPR2-10) or holoendemic (>75% PfPR2-10) areas decreased from 218·6 million (34·4%) of 635·7 million to 183·5 million (22·5%) of 815·7 million across 44 malaria-endemic countries. 280·1 million (34·3%) people lived in areas of mesoendemic transmission (>10% to 50% PfPR2-10) in 2010 compared with 178·6 million (28·1%) in 2000.,Population in areas of unstable or very low transmission (<5% PfPR2-10) increased from 131·7 million people (20·7%) in 2000 to 219·0 million (26·8%) in 2010.,An estimated 217·6 million people, or 26·7% of the 2010 population, lived in areas where transmission had reduced by at least one PfPR2-10 endemicity class. 40 countries showed a reduction in national mean PAPfPR2-10.,Only ten countries contributed 87·1% of the population living in areas of hyperendemic or holoendemic transmission in 2010.,Substantial reductions in malaria transmission have been achieved in endemic countries in Africa over the period 2000-10.,However, 57% of the population in 2010 continued to live in areas where transmission remains moderate to intense and global support to sustain and accelerate the reduction of transmission must remain a priority.,Wellcome Trust.

Suriname was a high malaria risk country before the introduction of a new five-year malaria control program in 2005, the Medical Mission Malaria Programme (MM-MP).,Malaria was endemic in the forested interior, where especially the stabile village communities were affected.,The interventions of the MM-MP included new strategies for prevention, vector control, case management, behavioral change communication (BCC)/information, education and communication (IEC), and strengthening of the health system (surveillance, monitoring and evaluation and epidemic detection system).,After a slow first year with non-satisfying scores for the performance indicators, the MM-MP truly engaged in its intervention activities in 2006 and kept its performance up until the end of 2009.,A total of 69,994 long-lasting insecticide-treated nets were distributed and more than 15,000 nets re-impregnated.,In high-risk areas, this was complemented with residual spraying of insecticides.,Over 10,000 people were screened with active case detection in outbreak and high-risk areas.,Additional notification points were established and the national health system was strengthened.,In the current paper, the MM-MP is evaluated both on account of the targets established within the programme and on account of its impact on the malaria situation in Suriname.,Malaria vector populations, monitored in sentinel sites, collapsed after 2006 and concurrently the number of national malaria cases decreased from 8,618 in 2005 to 1,509 in 2009.,Malaria transmission risk shifted from the stabile village communities to the mobile gold mining communities, especially those along the French Guiana border.,The novel strategies for malaria control introduced in Suriname within the MM-MP have led to a significant decrease in the national malaria burden.,The challenge is to further reduce malaria using the available strategies as appropriate in the affected areas and populations.,Elimination of malaria in the country will require a thorough understanding of transmission dynamics and a dedicated investment in key effective interventions.

Present elimination strategies are based on recommendations derived during the Global Malaria Eradication Program of the 1960s.,However, many countries considering elimination nowadays have high intrinsic transmission potential and, without the support of a regional campaign, have to deal with the constant threat of imported cases of the disease, emphasising the need to revisit the strategies on which contemporary elimination programmes are based.,To eliminate malaria, programmes need to concentrate on identification and elimination of foci of infections through both passive and active methods of case detection.,This approach needs appropriate treatment of both clinical cases and asymptomatic infections, combined with targeted vector control.,Draining of infectious pools entirely will not be sufficient since they could be replenished by imported malaria.,Elimination will thus additionally need identification and treatment of incoming infections before they lead to transmission, or, more realistically, embarking on regional initiatives to dry up importation at its source.

Alternatively activated macrophages (M2) have an important function in innate immune responses to parasitic helminths, and emerging evidence also indicates these cells are regulators of systemic metabolism.,Here we show a critical role for mTORC2 signalling in the generation of M2 macrophages.,Abrogation of mTORC2 signalling in macrophages by selective conditional deletion of the adaptor molecule Rictor inhibits the generation of M2 macrophages while leaving the generation of classically activated macrophages (M1) intact.,Selective deletion of Rictor in macrophages prevents M2 differentiation and clearance of a parasitic helminth infection in mice, and also abrogates the ability of mice to regulate brown fat and maintain core body temperature.,Our findings define a role for mTORC2 in macrophages in integrating signals from the immune microenvironment to promote innate type 2 immunity, and also to integrate systemic metabolic and thermogenic responses.,mTORC1 and mTORC2 are alternatively required for differentiation of T cells into Th1/Th17 or Th2 cells.,Here the authors show mTORC2 signalling is also needed for IL-4-induced M2 activation with functional evidence provided by a N. brasiliensis infection model and cold challenge to model adaptive thermogenesis.

Over the last decade a significant number of studies have highlighted the central role of host antimicrobial (or defence) peptides in modulating the response of innate immune cells to pathogen-associated ligands.,In humans, the most widely studied antimicrobial peptide is LL-37, a 37-residue peptide containing an amphipathic helix that is released via proteolytic cleavage of the precursor protein CAP18.,Owing to its ability to protect against lethal endotoxaemia and clinically-relevant bacterial infections, LL-37 and its derivatives are seen as attractive candidates for anti-sepsis therapies.,We have identified a novel family of molecules secreted by parasitic helminths (helminth defence molecules; HDMs) that exhibit similar biochemical and functional characteristics to human defence peptides, particularly CAP18.,The HDM secreted by Fasciola hepatica (FhHDM-1) adopts a predominantly α-helical structure in solution.,Processing of FhHDM-1 by F. hepatica cathepsin L1 releases a 34-residue C-terminal fragment containing a conserved amphipathic helix.,This is analogous to the proteolytic processing of CAP18 to release LL-37, which modulates innate cell activation by classical toll-like receptor (TLR) ligands such as lipopolysaccharide (LPS).,We show that full-length recombinant FhHDM-1 and a peptide analogue of the amphipathic C-terminus bind directly to LPS in a concentration-dependent manner, reducing its interaction with both LPS-binding protein (LBP) and the surface of macrophages.,Furthermore, FhHDM-1 and the amphipathic C-terminal peptide protect mice against LPS-induced inflammation by significantly reducing the release of inflammatory mediators from macrophages.,We propose that HDMs, by mimicking the function of host defence peptides, represent a novel family of innate cell modulators with therapeutic potential in anti-sepsis treatments and prevention of inflammation.

In lowland areas of Malaysia, Plasmodium knowlesi infection is associated with land use change and high proportions of the vector Anopheles balabacensis.,We conducted a 15-month study in two Malaysian villages to determine the effect of habitat on vector populations in understudied high-altitude, high-incidence districts.,Anopheles mosquitoes were sampled in human settlements, plantations and forest edges, and screened for Plasmodium species by PCR.,We report the first An. donaldi positive for P. knowlesi.,This potential vector was associated with habitat fragmentation measured as disturbed forest edge:area ratio, while An. balabacensis was not, indicating fragmented land use could favour An. donaldi.,Anopheline species richness and diversity decreased from forest edge, to plantation, to human settlement.,Greater numbers of An. balabacensis and An. donaldi were found in forest edges compared to human settlements, suggesting exposure to vectors and associated zoonoses may be greater for people entering this habitat.

The monkey malaria parasite Plasmodium knowlesi is now recognized as the fifth species of Plasmodium that can cause human malaria.,Like the region II of the Duffy binding protein of P. vivax (PvDBPII), the region II of the P. knowlesi Duffy binding protein (PkDBPαII) plays an essential role in the parasite’s invasion into the host’s erythrocyte.,Numerous polymorphism studies have been carried out on PvDBPII, but none has been reported on PkDBPαII.,In this study, the genetic diversity, haplotyes and allele groups of PkDBPαII of P. knowlesi clinical isolates from Peninsular Malaysia were investigated.,Blood samples from 20 knowlesi malaria patients and 2 wild monkeys (Macaca fascicularis) were used.,These samples were collected between 2010 and 2012.,The PkDBPαII region of the isolates was amplified by PCR, cloned into Escherichia coli, and sequenced.,The genetic diversity, natural selection and haplotypes of PkDBPαII were analysed using MEGA5 and DnaSP ver.,5.10.00 programmes.,Fifty-three PkDBPαII sequences from human infections and 6 from monkeys were obtained.,Comparison at the nucleotide level against P. knowlesi strain H as reference sequence showed 52 synonymous and 76 nonsynonymous mutations.,Analysis on the rate of these mutations indicated that PkDBPαII was under purifying (negative) selection.,At the amino acid level, 36 different PkDBPαII haplotypes were identified.,Twelve of the 20 human and 1 monkey blood samples had mixed haplotype infections.,These haplotypes were clustered into 2 distinct allele groups.,The majority of the haplotypes clustered into the large dominant group.,Our present study is the first to report the genetic diversity and natural selection of PkDBPαII.,Hence, the haplotypes described in this report can be considered as novel.,Although a high level of genetic diversity was observed, the PkDBPαII appeared to be under purifying selection.,The distribution of the haplotypes was skewed, with one dominant major and one minor group.,Future study should investigate PkDBPαII of P. knowlesi from Borneo, which hitherto has recorded the highest number of human knowlesi malaria.

No molecular data have been available on tick-borne pathogens that infect dogs from Angola.,The occurrence of agents from the genera Anaplasma, Babesia, Ehrlichia and Hepatozoon was assessed in 103 domestic dogs from Luanda, by means of the polymerase chain reaction (PCR) and DNA sequence analysis.,Forty-six dogs (44.7 %) were positive for at least one pathogen.,Twenty-one animals (20.4 %) were found infected with Anaplasma platys, 18 (17.5 %) with Hepatozoon canis, six (5.8 %) with Ehrlichia canis, six (5.8 %) with Babesia vogeli, one (1.0 %) with Babesia gibsoni and one (1.0 %) with an unnamed Babesia sp.,The molecular frequency of single infections taken together was 37.9 % and that of co-infections with several combinations of two pathogens accounted for 6.8 % of the animals.,This is the first report of A. platys, B. vogeli, B. gibsoni, E. canis and H. canis infections diagnosed by PCR in domestic dogs from Angola.,The present study provides evidence that dogs in Luanda are widely exposed to, and at risk of becoming infected with, tick-borne pathogens.,Further investigation is needed, including a larger number of animals, canine populations from other cities and provinces of the country, as well as potential vector ticks, aiming at better characterizing and controlling canine vector-borne diseases in Angola.

Although Ixodes spp. are the most common ticks in North-Western Europe, recent reports indicated an expanding geographical distribution of Dermacentor reticulatus in Western Europe.,Recently, the establishment of a D. reticulatus population in Belgium was described.,D. reticulatus is an important vector of canine and equine babesiosis and can transmit several Rickettsia species, Coxiella burnetii and tick-borne encephalitis virus (TBEV), whilst Ixodes spp. are vectors of pathogens causing babesiosis, borreliosis, anaplasmosis, rickettsiosis and TBEV.,A survey was conducted in 2008-2009 to investigate the presence of different tick species and associated pathogens on dogs and cats in Belgium.,Ticks were collected from dogs and cats in 75 veterinary practices, selected by stratified randomization.,All collected ticks were morphologically determined and analysed for the presence of Babesia spp., Borrelia spp., Anaplasma phagocytophilum and Rickettsia DNA.,In total 2373 ticks were collected from 647 dogs and 506 cats.,Ixodes ricinus (76.4%) and I. hexagonus (22.6%) were the predominant species.,Rhipicephalus sanguineus (0.3%) and D. reticulatus (0.8%) were found in low numbers on dogs only.,All dogs infested with R. sanguineus had a recent travel history, but D. reticulatus were collected from a dog without a history of travelling abroad.,Of the collected Ixodes ticks, 19.5% were positive for A. phagocytophilum and 10.1% for Borrelia spp.,(B. afzelii, B. garinii, B. burgdorferi s.s., B. lusitaniae, B. valaisiana and B. spielmanii).,Rickettsia helvetica was found in 14.1% of Ixodes ticks.,All Dermacentor ticks were negative for all the investigated pathogens, but one R. sanguineus tick was positive for Rickettsia massiliae.,D. reticulatus was confirmed to be present as an indigenous parasite in Belgium.,B. lusitaniae and R. helvetica were detected in ticks in Belgium for the first time.

The proportion of mosquito blood-meals that are of human origin, referred to as the ‘human blood index’ or HBI, is a key determinant of malaria transmission.,A systematic review was conducted followed by meta-regression of the HBI for the major African malaria vectors.,Evidence is presented for higher HBI among Anopheles gambiae (M/S forms and Anopheles coluzzii/An. gambiae sensu stricto are not distinguished for most studies and, therefore, combined) as well as Anopheles funestus when compared with Anopheles arabiensis (prevalence odds ratio adjusted for collection location [i.e. indoor or outdoor]: 1.62; 95% CI 1.09-2.42; 1.84; 95% CI 1.35-2.52, respectively).,This finding is in keeping with the entomological literature which describes An. arabiensis to be more zoophagic than the other major African vectors.,However, analysis also revealed that HBI was more associated with location of mosquito captures (R2 = 0.29) than with mosquito (sibling) species (R2 = 0.11).,These findings call into question the appropriateness of current methods of assessing host preferences among disease vectors and have important implications for strategizing vector control.,The online version of this article (10.1186/s12936-018-2632-7) contains supplementary material, which is available to authorized users.

Philippa West and colleagues compare Plasmodium falciparum infection prevalence in children, anemia in young children, and entomological inoculation rate between study arms.,Please see later in the article for the Editors' Summary,Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) of houses provide effective malaria transmission control.,There is conflicting evidence about whether it is more beneficial to provide both interventions in combination.,A cluster randomised controlled trial was conducted to investigate whether the combination provides added protection compared to ITNs alone.,In northwest Tanzania, 50 clusters (village areas) were randomly allocated to ITNs only or ITNs and IRS.,Dwellings in the ITN+IRS arm were sprayed with two rounds of bendiocarb in 2012.,Plasmodium falciparum prevalence rate (PfPR) in children 0.5-14 y old (primary outcome) and anaemia in children <5 y old (secondary outcome) were compared between study arms using three cross-sectional household surveys in 2012.,Entomological inoculation rate (secondary outcome) was compared between study arms.,IRS coverage was approximately 90%.,ITN use ranged from 36% to 50%.,In intention-to-treat analysis, mean PfPR was 13% in the ITN+IRS arm and 26% in the ITN only arm, odds ratio = 0.43 (95% CI 0.19-0.97, n = 13,146).,The strongest effect was observed in the peak transmission season, 6 mo after the first IRS.,Subgroup analysis showed that ITN users were additionally protected if their houses were sprayed.,Mean monthly entomological inoculation rate was non-significantly lower in the ITN+IRS arm than in the ITN only arm, rate ratio = 0.17 (95% CI 0.03-1.08).,This is the first randomised trial to our knowledge that reports significant added protection from combining IRS and ITNs compared to ITNs alone.,The effect is likely to be attributable to IRS providing added protection to ITN users as well as compensating for inadequate ITN use.,Policy makers should consider deploying IRS in combination with ITNs to control transmission if local ITN strategies on their own are insufficiently effective.,Given the uncertain generalisability of these findings, it would be prudent for malaria control programmes to evaluate the cost-effectiveness of deploying the combination.,www.ClinicalTrials.govNCT01697852,Please see later in the article for the Editors' Summary,Every year, more than 200 million cases of malaria occur worldwide, and more than 600,000 people, mainly children living in sub-Saharan Africa, die from this parasitic infection.,Malaria parasites, which are transmitted to people through the bites of infected night-flying mosquitoes, cause a characteristic fever that needs to be treated promptly with antimalarial drugs to prevent anaemia (a reduction in red blood cell numbers) and organ damage.,Prompt treatment also helps to reduce malaria transmission, but the mainstays of global malaria control efforts are the provision of insecticide-treated nets (ITNs) for people to sleep under to avoid mosquito bites, and indoor residual spraying (IRS) of houses with insecticides, which prevents mosquitoes from resting in houses.,Both approaches have been scaled up in the past decade.,About 54% of households in Africa now own at least one ITN, and 8% of at-risk populations are protected by IRS.,As a result of the widespread deployment of these preventative tools and the increased availability of effective antimalarial drugs, malaria-related deaths in Africa fell by 45% between 2000 and 2012.,Some countries have chosen to use ITNs and IRS in combination, reasoning that this will increase the proportion of individuals who are protected by at least one intervention and may provide additional protection to people using both interventions rather than one alone.,However, providing both interventions is costly, so it is important to know whether this rationale is correct.,In this cluster randomised controlled trial (a study that compares outcomes of groups of people randomly assigned to receive different interventions) undertaken in the Muleba District of Tanzania during 2012, the researchers investigate whether ITNs plus IRS provide more protection against malaria than ITNs alone.,Malaria transmission occurs throughout the year in Muleba District but peaks after the October-December and March-May rains.,Ninety-one percent of the district's households own at least one ITN, and 58% of households own enough ITNs to cover all their sleeping places.,Annual rounds of IRS have been conducted in the region since 2007.,The researchers allocated 50 communities to the ITN intervention or to the ITN+IRS intervention.,Dwellings allocated to ITN+IRS were sprayed with insecticide just before each of the malaria transmission peaks in 2012.,The researchers used household surveys to collect information about ITN coverage in the study population, the proportion of children aged 0.5-14 years infected with the malaria parasite Plasmodium falciparum (the prevalence of infection), and the proportion of children under five years old with anaemia.,IRS coverage in the ITN+IRS arm was approximately 90%, and 50% of the children in both intervention arms used ITNs at the start of the trial, declining to 36% at the end of the study.,In an intention-to-treat analysis (which assumed that all study participants got the planned intervention), the average prevalence of infection was 13% in the ITN+IRS arm and 26% in the ITN arm.,A per-protocol analysis (which considered data only from participants who received their allocated intervention) indicated that the combined intervention had a statistically significant protective effect on the prevalence of infection compared to ITNs alone (an effect that is unlikely to have arisen by chance).,Finally, the proportion of young children with anaemia was lower in the ITN+IRS arm than in the ITN arm, but this effect was not statistically significant.,These findings provide evidence that IRS, when used in combination with ITNs, can provide better protection against malaria infection than ITNs used alone.,This effect is likely to be the result of IRS providing added protection to ITN users as well as compensating for inadequate ITN use.,The findings also suggest that the combination of interventions may reduce the prevalence of anaemia better than ITNs alone, but this result needs to be confirmed.,Additional trials are also needed to investigate whether ITN+IRS compared to ITN reduces clinical cases of malaria, and whether similar effects are seen in other settings.,Moreover, the cost-effectiveness of ITN+IRS and ITN alone needs to be compared.,For now, though, these findings suggest that national malaria control programs should consider implementing IRS in combination with ITNs if local ITN strategies alone are insufficiently effective and cannot be improved.,Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001630.,Information is available from the World Health Organization on malaria (in several languages), including information on insecticide-treated bed nets and indoor residual spraying; the World Malaria Report 2013 provides details of the current global malaria situation,The US Centers for Disease Control and Prevention provides information on malaria, on insecticide-treated bed nets, and on indoor residual spraying; it also provides 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 (in English and French); its website includes fact sheets about malaria in Africa and about nets and insecticides,MedlinePlus provides links to additional information on malaria (in English and Spanish)

Parasites play pivotal roles in host population dynamics and can have strong ecological impacts on hosts.,Knowledge of the effects of parasites on hosts is often limited by the general observation of a fraction of individuals (mostly adults) within a population.,The aim of this study was to assess the prevalence of malaria parasites in adult (≥1 year old) and nestling (7-11 day old) Tawny pipits Anthus campestris, to evaluate the influence of the host sex on parasite prevalence in both groups of age, and explore the association between infections and body condition (adults) and growth (nestlings).,Two hundred Tawny pipits (105 adults and 95 nestlings) from one Spanish population were screened for avian malaria parasites (Haemoproteus and Plasmodium) using the polymerase chain reaction (PCR)-based methods.,Body condition (body mass against a linear measure of size) was measured in adults and growth rate (daily mass gain) was calculated for nestlings.,The overall prevalence of infection was 46 %.,Sixteen different mitochondrial cytochrome b haplotypes of Plasmodium spp. and one Haemoproteus spp. haplotype were found.,Malaria parasites were equally prevalent in nestlings and adults (45 and 46 %, respectively).,Males were more likely to be infected by parasites than females, and this sex-bias parasitism was evident in both adults and nestlings.,Furthermore, a lower daily mass gain during nestling growth in males than in females following infections were found, whereas the effect of infections on body condition of adults was detrimental for females but not for males.,Age-specific differences in physiological trade-offs and ecological factors, such as nest predation would explain, at least in part, the observed host sex and age-related patterns in Tawny pipits.

Invasive species can displace natives, and thus identifying the traits that make aliens successful is crucial for predicting and preventing biodiversity loss.,Pathogens may play an important role in the invasive process, facilitating colonization of their hosts in new continents and islands.,According to the Novel Weapon Hypothesis, colonizers may out-compete local native species by bringing with them novel pathogens to which native species are not adapted.,In contrast, the Enemy Release Hypothesis suggests that flourishing colonizers are successful because they have left their pathogens behind.,To assess the role of avian malaria and related haemosporidian parasites in the global spread of a common invasive bird, we examined the prevalence and genetic diversity of haemosporidian parasites (order Haemosporida, genera Plasmodium and Haemoproteus) infecting house sparrows (Passer domesticus).,We sampled house sparrows (N = 1820) from 58 locations on 6 continents.,All the samples were tested using PCR-based methods; blood films from the PCR-positive birds were examined microscopically to identify parasite species.,The results show that haemosporidian parasites in the house sparrows' native range are replaced by species from local host-generalist parasite fauna in the alien environments of North and South America.,Furthermore, sparrows in colonized regions displayed a lower diversity and prevalence of parasite infections.,Because the house sparrow lost its native parasites when colonizing the American continents, the release from these natural enemies may have facilitated its invasion in the last two centuries.,Our findings therefore reject the Novel Weapon Hypothesis and are concordant with the Enemy Release Hypothesis.

To accelerate progress against malaria in high burden countries, a strategic reorientation of resources at the sub-national level is needed.,This paper describes how mathematical modelling was used in mainland Tanzania to support the strategic revision that followed the mid-term review of the 2015-2020 national malaria strategic plan (NMSP) and the epidemiological risk stratification at the council level in 2018.,Intervention mixes, selected by the National Malaria Control Programme, were simulated for each malaria risk strata per council.,Intervention mixes included combinations of insecticide-treated bed nets (ITN), indoor residual spraying, larval source management, and intermittent preventive therapies for school children (IPTsc).,Effective case management was either based on estimates from the malaria indicator survey in 2016 or set to a hypothetical target of 85%.,A previously calibrated mathematical model in OpenMalaria was used to compare intervention impact predictions for prevalence and incidence between 2016 and 2020, or 2022.,For each malaria risk stratum four to ten intervention mixes were explored.,In the low-risk and urban strata, the scenario without a ITN mass campaign in 2019, predicted high increase in prevalence by 2020 and 2022, while in the very-low strata the target prevalence of less than 1% was maintained at low pre-intervention transmission intensity and high case management.,In the moderate and high strata, IPTsc in addition to existing vector control was predicted to reduce the incidence by an additional 15% and prevalence by 22%.,In the high-risk strata, all interventions together reached a maximum reduction of 76%, with around 70% of that reduction attributable to high case management and ITNs.,Overall, the simulated revised NMSP was predicted to achieve a slightly lower prevalence in 2020 compared to the 2015-2020 NMSP (5.3% vs 6.3%).,Modelling supported the choice of intervention per malaria risk strata by providing impact comparisons of various alternative intervention mixes to address specific questions relevant to the country.,The use of a council-calibrated model, that reproduces local malaria trends, represents a useful tool for compiling available evidence into a single analytical platform, that complement other evidence, to aid national programmes with decision-making processes.,The online version contains supplementary material available at 10.1186/s12936-022-04099-5.

Malaria rapid diagnostic tests (RDTs) primarily detect Plasmodium falciparum antigen histidine-rich protein 2 (HRP2) and the malaria-conserved antigen lactate dehydrogenase (LDH) for P. vivax and other malaria species.,The performance of RDTs and their utility is dependent on circulating antigen concentration distributions in infected individuals in a population in which malaria is endemic and on the limit of detection of the RDT for the antigens.,Malaria rapid diagnostic tests (RDTs) primarily detect Plasmodium falciparum antigen histidine-rich protein 2 (HRP2) and the malaria-conserved antigen lactate dehydrogenase (LDH) for P. vivax and other malaria species.,The performance of RDTs and their utility is dependent on circulating antigen concentration distributions in infected individuals in a population in which malaria is endemic and on the limit of detection of the RDT for the antigens.,A multiplexed immunoassay for the quantification of HRP2, P. vivax LDH, and all-malaria LDH (pan LDH) was developed to accurately measure circulating antigen concentration and antigen distribution in a population with endemic malaria.,The assay also measures C-reactive protein (CRP) levels as an indicator of inflammation.,Validation was conducted with clinical specimens from 397 asymptomatic donors from Myanmar and Uganda, confirmed by PCR for infection, and from participants in induced blood-stage malaria challenge studies.,The assay lower limits of detection for HRP2, pan LDH, P. vivax LDH, and CRP were 0.2 pg/ml, 9.3 pg/ml, 1.5 pg/ml, and 26.6 ng/ml, respectively.,At thresholds for HRP2, pan LDH, and P. vivax LDH of 2.3 pg/ml, 47.8 pg/ml, and 75.1 pg/ml, respectively, and a specificity ≥98.5%, the sensitivities for ultrasensitive PCR-confirmed infections were 93.4%, 84.9%, and 48.9%, respectively.,Plasmodium LDH (pLDH) concentration, in contrast to that of HRP2, correlated closely with parasite density.,CRP levels were moderately higher in P. falciparum infections with confirmed antigenemia versus those in clinical specimens with no antigen.,The 4-plex array is a sensitive tool for quantifying diagnostic antigens in malaria infections and supporting the evaluation of new ultrasensitive RDTs.

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.

In the past decade, there has been rapid scale-up of insecticide-based malaria vector control in the context of integrated vector management (IVM) according to World Health Organization recommendations.,Endemic countries have deployed indoor residual spraying (IRS) and long-lasting insecticidal nets as hallmark vector control interventions.,This paper discusses the successes and continued challenges and the way forward for the IRS programme in Malawi.,The National Malaria Control Programme in Malawi, with its efforts to implement an integrated approach to malaria vector control, was the ‘case’ for this study.,Information sources included all available data and accessible archived documentary records on IRS in Malawi.,A methodical assessment of published and unpublished documents was conducted via a literature search of online electronic databases.,Malawi has implemented IRS as the main malaria transmission-reducing intervention.,However, pyrethroid and carbamate resistance in malaria vectors has been detected extensively across the country and has adversely affected the IRS programme.,Additionally, IRS activities have been characterized by substantial inherent logistical and technical challenges culminating into missed targets.,As a consequence, programmatic IRS operations have been scaled down from seven districts in 2010 to only one district in 2014.,The future of the IRS programme in Malawi is uncertain due to limited funding, high cost of alternative insecticides and technical resource challenges being experienced in the country.,The availability of a long-lasting formulation of the organophosphate pirimiphos-methyl makes the re-introduction of IRS a possibility and may be a useful approach for the management of pyrethroid resistance.,Implementing the IVM strategy, advocating for sustainable domestic funding, including developing an insecticide resistance monitoring and management plan and vector surveillance guidelines will be pivotal in steering entomologic monitoring and future vector control activities in Malawi.

Chloroquine resistance (CR) decreased after the removal of chloroquine from national treatment guidelines in Malawi, Kenia and Tanzania.,In this investigation the prevalence of the chloroquine resistance (CQR) conferring mutant pfcrt allele and its associated chromosomal haplotype were determined before and after the change in Gabonese national treatment guidelines from chloroquine (CQ) to artesunate plus amodiaquine (AQ) in 2003.,The prevalence of the wild type pfcrt allele was assessed in 144 isolates from the years 2005 - 07 by PCR fragment restriction digest and direct sequencing.,For haplotype analysis of the chromosomal regions flanking the pfcrt locus, microsatellite analysis was done on a total of 145 isolates obtained in 1995/96 (43 isolates), 2002 (47 isolates) and 2005 - 07 (55 isolates).,The prevalence of the mutant pfcrt allele decreased from 100% in the years 1995/96 and 2002 to 97% in 2005 - 07.,Haplotype analysis showed that in 1995/96 79% of the isolates carried the same microsatellite alleles in a chromosomal fragment spanning 39 kb surrounding the pfcrt locus.,In 2002 and 2005 - 07 the prevalence of this haplotype was 62% and 58%, respectively.,Pfcrt haplotype analysis showed that all wild type alleles were CVMNK.,Four years after the withdrawal of CQ from national treatment guidelines the prevalence of the mutant pfcrt allele remains at 97%.,The data suggest that the combination of artesunate plus AQ may result in continued selection for the mutant pfcrt haplotype even after discontinuance of CQ usage.

Over the past decade malaria intervention coverage has been scaled up across Africa.,However, it remains unclear what overall reduction in transmission is achievable using currently available tools.,We developed an individual-based simulation model for Plasmodium falciparum transmission in an African context incorporating the three major vector species (Anopheles gambiae s.s., An. arabiensis, and An. funestus) with parameters obtained by fitting to parasite prevalence data from 34 transmission settings across Africa.,We incorporated the effect of the switch to artemisinin-combination therapy (ACT) and increasing coverage of long-lasting insecticide treated nets (LLINs) from the year 2000 onwards.,We then explored the impact on transmission of continued roll-out of LLINs, additional rounds of indoor residual spraying (IRS), mass screening and treatment (MSAT), and a future RTS,S/AS01 vaccine in six representative settings with varying transmission intensity (as summarized by the annual entomological inoculation rate, EIR: 1 setting with low, 3 with moderate, and 2 with high EIRs), vector-species combinations, and patterns of seasonality.,In all settings we considered a realistic target of 80% coverage of interventions.,In the low-transmission setting (EIR∼3 ibppy [infectious bites per person per year]), LLINs have the potential to reduce malaria transmission to low levels (<1% parasite prevalence in all age-groups) provided usage levels are high and sustained.,In two of the moderate-transmission settings (EIR∼43 and 81 ibppy), additional rounds of IRS with DDT coupled with MSAT could drive parasite prevalence below a 1% threshold.,However, in the third (EIR = 46) with An. arabiensis prevailing, these interventions are insufficient to reach this threshold.,In both high-transmission settings (EIR∼586 and 675 ibppy), either unrealistically high coverage levels (>90%) or novel tools and/or substantial social improvements will be required, although considerable reductions in prevalence can be achieved with existing tools and realistic coverage levels.,Interventions using current tools can result in major reductions in P. falciparum malaria transmission and the associated disease burden in Africa.,Reduction to the 1% parasite prevalence threshold is possible in low- to moderate-transmission settings when vectors are primarily endophilic (indoor-resting), provided a comprehensive and sustained intervention program is achieved through roll-out of interventions.,In high-transmission settings and those in which vectors are mainly exophilic (outdoor-resting), additional new tools that target exophagic (outdoor-biting), exophilic, and partly zoophagic mosquitoes will be required.,Please see later in the article for the Editors' Summary,Half the world's population is at risk of malaria, and every year nearly one million people-mainly children living in sub-Saharan Africa-die from this mosquito-borne parasitic disease.,Most malarial deaths are caused by Plasmodium falciparum, which is transmitted to people by mainly night-biting Anopheles mosquitoes.,When infected mosquitoes feed on people, they inject sporozoites, a parasitic form 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 more red blood cells.,This increase in the parasitic burden causes malaria's characteristic fever.,Infected red blood cells also release “gametocytes,” which infect mosquitoes when they take a blood meal.,In the mosquito, the gametocytes multiply and develop into sporozoites, thus completing the parasite's life cycle.,Malaria can be prevented by spraying the insides of houses (where most Anopheles species feed and rest) with insecticides (indoor residual spraying, IRS) and by sleeping under bed nets that have been treated with long-lasting insecticides (long-lasting insecticide nets, LLINs).,Mass screening and treatment (MSAT) with effective antimalarial drugs can also reduce malaria transmission.,Early attempts to eradicate malaria (reduce its global incidence to zero) in the 1950s reduced the incidence of malaria to zero in some countries (malaria elimination) and greatly reduced malarial illnesses and deaths in others (malaria control).,However, this eradication program was aborted in the 1970s in part because of emerging drug and insecticide resistance.,Recently, the advent of artemisinin-based combination therapies and new insecticides and the prospect of a malaria vaccine have renewed interest in controlling, eliminating, and ultimately eradicating malaria.,Consequently, in September 2008, the Roll Back Malaria Partnership launched the Global Malaria Action Plan, which aims to reduce malaria deaths to near zero by 2015.,But are the currently available tools for reducing malaria transmission sufficient to control and eliminate malaria in Africa, the continent where most malaria deaths occur?,In this study, the researchers use a new mathematical model of P. falciparum transmission to investigate this question.,The researchers' P. falciparum transmission model consists of “compartments” through which individuals pass as they become infected with parasites, develop immunity, become infectious to mosquitoes, and so on.,The researchers used published data about parasite prevalence (the proportion of the population infected with parasites) and about relevant aspects of mosquito, parasite, and human biology, to estimate the chances of an individual moving between compartments.,Finally, they used the model to explore the impact over 25 years of increased coverage of LLINs, IRS, and MSAT, and of a future vaccine on malaria transmission in six representative African settings.,In a low-transmission setting, 80% coverage with LLINs reduced the parasite prevalence to below 1% in all age groups.,In two moderate-transmission settings, LLIN scale-up alone failed to reach this target but the addition of IRS and MSAT drove the parasite prevalence below 1%.,However, this combination of interventions did not control malaria in a moderate-transmission setting in which a mosquito species that bites and rests outside houses contributes to malaria transmission.,Finally, in two high-transmission settings, parasite prevalence could be driven below 1% only by setting unrealistic coverage targets for existing interventions.,This new mathematical model greatly simplifies the complex dynamics of malaria transmission and includes several assumptions about which there is considerable uncertainty.,The findings of this study are not, therefore, firm predictions of the future of malaria control in specific settings.,Nevertheless, they suggest that it should be possible to make large reductions in malaria transmission and the associated disease burden in Africa over the next 25 years using currently available tools.,Specifically, in regions where transmission is low or moderate and mosquitoes mainly feed indoors, it should be possible to reduce parasite prevalence to less than 1% provided a sustained intervention program is achieved.,Importantly, however, these findings suggest that in regions where malaria transmission is high or where mosquitoes rest and bite outside houses, new approaches will be needed to control and eliminate malaria.,Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000324.,Information is available from the World Health Organization on malaria (in several languages); the 2009 World Malaria Report provides details of the current global malaria situation,The US Centers for Disease Control and Prevention provide information on malaria (in English and Spanish),Information is available from the Roll Back Malaria Partnership on its approach to the global control of malaria, including the Global Malaria Action Plan and a fact sheet on malaria in Africa,MedlinePlus provides links to additional information on malaria (in English and Spanish)

Invasion of erythrocytes by Plasmodium falciparum merozoites is necessary for malaria pathogenesis and is therefore a primary target for vaccine development.,RH5 is a leading subunit vaccine candidate because anti-RH5 antibodies inhibit parasite growth and the interaction with its erythrocyte receptor basigin is essential for invasion.,RH5 is secreted, complexes with other parasite proteins including CyRPA and RIPR, and contains a conserved N-terminal region (RH5Nt) of unknown function that is cleaved from the native protein.,Here, we identify P113 as a merozoite surface protein that directly interacts with RH5Nt.,Using recombinant proteins and a sensitive protein interaction assay, we establish the binding interdependencies of all the other known RH5 complex components and conclude that the RH5Nt-P113 interaction provides a releasable mechanism for anchoring RH5 to the merozoite surface.,We exploit these findings to design a chemically synthesized peptide corresponding to RH5Nt, which could contribute to a cost-effective malaria vaccine.,The secreted Plasmodium falciparum protein RH5 is essential for invasion of erythrocytes and is a promising vaccine candidate.,Here, Galaway et al. show that the N-terminal region of RH5 binds the GPI-anchored merozoite surface protein P113 and can elicit invasion-blocking antibodies.

Malaria parasite infection is initiated by the mosquito-transmitted sporozoite stage, a highly motile invasive cell that targets hepatocytes in the liver for infection.,A promising approach to developing a malaria vaccine is the use of proteins located on the sporozoite surface as antigens to elicit humoral immune responses that prevent the establishment of infection.,Very little of the P. falciparum genome has been considered as potential vaccine targets, and candidate vaccines have been almost exclusively based on single antigens, generating the need for novel target identification.,The most advanced malaria vaccine to date, RTS,S, a subunit vaccine consisting of a portion of the major surface protein circumsporozoite protein (CSP), conferred limited protection in Phase III trials, falling short of community-established vaccine efficacy goals.,In striking contrast to the limited protection seen in current vaccine trials, sterilizing immunity can be achieved by immunization with radiation-attenuated sporozoites, suggesting that more potent protection may be achievable with a multivalent protein vaccine.,Here, we provide the most comprehensive analysis to date of proteins located on the surface of or secreted by Plasmodium falciparum salivary gland sporozoites.,We used chemical labeling to isolate surface-exposed proteins on sporozoites and identified these proteins by mass spectrometry.,We validated several of these targets and also provide evidence that components of the inner membrane complex are in fact surface-exposed and accessible to antibodies in live sporozoites.,Finally, our mass spectrometry data provide the first direct evidence that the Plasmodium surface proteins CSP and TRAP are glycosylated in sporozoites, a finding that could impact the selection of vaccine antigens.

Malaria is still a major public health concern in the Democratic Republic of Congo.,Its morbidity and mortality challenge the actual strategies of the fight agains malaria.,This study was aimed to describe the epidemiology, the clinical caracteristics and the risk factors of death associated to severe malaria in the pediatric population under 5 years at Sendwe Hospital of Lubumbashi.,This analytical retrospective study was conducted in Lubumbashi, in the province of Haut-Katanga.,All patients under 5 years hospitalized for severe malaria were registered from January 2014 to December 2016.,Among the 3,092 patients hospitalised during our study period, 452 (14.6%) were admitted for severe malaria.,The average age was 27.04 months, the male sex was the most affected (53.54% with the sex-ratio 1.15).,The most frequent forms of gravity noticed were cerebral malaria (48.23%) and severe anemia (46.90%).,Death was noted in the evolution in 28.32%.,Repeated convulsion (OR = 2.27; 95% CI: 1.47-3.48), coma (OR = 3.55; 95% CI: 2.19-5.74) and severe acute malnutrition (OR = 3.32; 95% CI: 1.56-7.06) were asscociated with a high risk of death.,This research shows that severe malaria is still an important cause of morbidity and mortality among young children in Lubumbashi.,Neurologic and anemic forms are the most frequent.,The predictive signs of death are: repeated convulsions, coma and severe acute malnutrition.

The impacts of interannual climate fluctuations on vector-borne diseases, especially malaria, have received considerable attention in the scientific literature.,These effects can be significant in semi-arid and high-elevation areas such as the highlands of East Africa because cooler temperature and seasonally dry conditions limit malaria transmission.,Many previous studies have examined short-term lagged effects of climate on malaria (weeks to months), but fewer have explored the possibility of longer-term seasonal effects.,This study assessed the interannual variability of malaria occurrence from 2001 to 2009 in the Amhara region of Ethiopia.,We tested for associations of climate variables summarized during the dry (January-April), early transition (May-June), and wet (July-September) seasons with malaria incidence in the early peak (May-July) and late peak (September-December) epidemic seasons using generalized linear models.,Climate variables included land surface temperature (LST), rainfall, actual evapotranspiration (ET), and the enhanced vegetation index (EVI).,We found that both early and late peak malaria incidence had the strongest associations with meteorological conditions in the preceding dry and early transition seasons.,Temperature had the strongest influence in the wetter western districts, whereas moisture variables had the strongest influence in the drier eastern districts.,We also found a significant correlation between malaria incidence in the early and the subsquent late peak malaria seasons, and the addition of early peak malaria incidence as a predictor substantially improved models of late peak season malaria in both of the study sub-regions.,These findings suggest that climatic effects on malaria prior to the main rainy season can carry over through the rainy season and affect the probability of malaria epidemics during the late malaria peak.,The results also emphasize the value of combining environmental monitoring with epidemiological surveillance to develop forecasts of malaria outbreaks, as well as the need for spatially stratified approaches that reflect the differential effects of climatic variations in the different sub-regions.

North-west Ethiopia faces the highest burden world-wide of visceral leishmaniasis (VL) and HIV co-infection.,VL-HIV co-infected patients have higher (initial) parasitological failure and relapse rates than HIV-negative VL patients.,Whereas secondary prophylaxis reduces the relapse rate, parasitological failure rates remain high with the available antileishmanial drugs, especially when administered as monotherapy.,We aimed to determine the initial effectiveness (parasitologically-confirmed cure) of a combination of liposomal amphotericin B (AmBisome) and miltefosine for treatment of VL in HIV co-infected patients.,We conducted a retrospective cohort study at a Médecins Sans Frontières-supported health center in north-west Ethiopia.,We included VL-HIV co-infected adults, treated for VL between January 2011 and August 2014, with AmBisome infusion (30 mg/kg total dose) and miltefosine orally for 28 days (100 mg/day).,Proportions of initial treatment outcome categories were calculated.,Predictors of initial parasitological failure and of death were determined using multivariable logistic regression.,Of the 173 patients included, 170 (98.3%) were male and the median age was 32 years.,The proportion of patients with primary VL (48.0%) and relapse VL (52.0%) were similar.,The majority had advanced HIV disease (n = 111; 73.5%) and were on antiretroviral therapy prior to VL diagnosis (n = 106; 64.2%).,Initial cure rate was 83.8% (95% confidence interval [CI], 77.6-88.6); death rate 12.7% (95% CI, 8.5-18.5) and parasitological failure rate 3.5% (95% CI, 1.6-7.4).,Tuberculosis co-infection at VL diagnosis was predictive of parasitological failure (adjusted odds ratio (aOR), 8.14; p = 0.02).,Predictors of death were age >40 years (aOR, 5.10; p = 0.009), hemoglobin ≤6.5 g/dL (aOR, 5.20; p = 0.002) and primary VL (aOR, 8.33; p = 0.001).,Initial parasitological failure rates were very low with AmBisome and miltefosine combination therapy.,This regimen seems a suitable treatment option.,Knowledge of predictors of poor outcome may facilitate better management.,These findings remain to be confirmed in clinical trials.

Antimonials are still being used for visceral leishmaniasis (VL) treatment among HIV co-infected patients in East-Africa due to the shortage of alternative safer drugs like liposomal amphotericin B.,Besides tolerability, emergence of resistance to antimonials is a major concern.,This study was aimed at assessing the clinical outcome of VL-HIV co-infected patients when treated with sodium stibogluconate (SSG).,Retrospective patient record analysis of VL-HIV co-infected patients treated at a clinical trial site in north-west Ethiopia was done.,Patients with parasitologically confirmed VL and HIV co-infection treated with SSG were included.,The dose of SSG used was 20 mg Sb5 (pentavalent antimony)/kg and maximum of 850 mg Sb5 for 30 days.,The clinical outcomes were defined based on the tissue aspiration results as cure or failure, and additionally the safety and mortality rates were computed.,The study included 57 patients treated with SSG and by the end of treatment only 43.9% of patients were cured.,The parasitological treatment failure and the case fatality rate were 31.6% and 14.0% respectively.,SSG was discontinued temporarily or permanently for 12 (21.1%) cases due to safety issues.,High baseline parasite load (graded more than 4+) was significantly associated with treatment failure (odds ratio = 8.9, 95% confidence interval = .5-51.7).,SSG is not only unsafe, but also has low effectiveness for VL-HIV patients.,Safe and effective alternative medications are very urgently needed.,Drug sensitivity surveillance should be introduced in the region.

In order to better understand the epidemiology of Human and Animal trypanosomiasis that occur together in sleeping sickness foci, a study of prevalences of animal parasites (Trypanosoma vivax, T. congolense “forest type”, and T. simiae) infections was conducted on domestic animals to complete the previous work carried on T. brucei gambiense prevalence using the same animal sample. 875 domestic animals, including 307 pigs, 264 goats, 267 sheep and 37 dogs were sampled in the sleeping sickness foci of Bipindi, Campo, Doumé and Fontem in Cameroon.,The polymerase chain reaction (PCR) based method was used to identify these trypanosome species.,A total of 237 (27.08%) domestic animals were infected by at least one trypanosome species.,The prevalence of T. vivax, T. congolense “forest type” and T. simiae were 20.91%, 11.42% and 0.34% respectively.,The prevalences of T. vivax and T. congolense “forest type” differed significantly between the animal species and between the foci (p < 0.0001); however, these two trypanosomes were found in all animal species as well as in all the foci subjected to the study.,The high prevalences of T. vivax and T. congolense “forest type” in Bipindi and Fontem-Center indicate their intense transmission in these foci.

A range of molecular amplification techniques have been developed for the diagnosis of Human African Trypanosomiasis (HAT); however, careful evaluation of these tests must precede implementation to ensure their high clinical accuracy.,Here, we investigated the diagnostic accuracy of molecular amplification tests for HAT, the quality of articles and reasons for variation in accuracy.,Data from studies assessing diagnostic molecular amplification tests were extracted and pooled to calculate accuracy.,Articles were included if they reported sensitivity and specificity or data whereby values could be calculated.,Study quality was assessed using QUADAS and selected studies were analysed using the bivariate random effects model.,16 articles evaluating molecular amplification tests fulfilled the inclusion criteria: PCR (n = 12), NASBA (n = 2), LAMP (n = 1) and a study comparing PCR and NASBA (n = 1).,Fourteen articles, including 19 different studies were included in the meta-analysis.,Summary sensitivity for PCR on blood was 99.0% (95% CI 92.8 to 99.9) and the specificity was 97.7% (95% CI 93.0 to 99.3).,Differences in study design and readout method did not significantly change estimates although use of satellite DNA as a target significantly lowers specificity.,Sensitivity and specificity of PCR on CSF for staging varied from 87.6% to 100%, and 55.6% to 82.9% respectively.,Here, PCR seems to have sufficient accuracy to replace microscopy where facilities allow, although this conclusion is based on multiple reference standards and a patient population that was not always representative.,Future studies should, therefore, include patients for which PCR may become the test of choice and consider well designed diagnostic accuracy studies to provide extra evidence on the value of PCR in practice.,Another use of PCR for control of disease could be to screen samples collected from rural areas and test in reference laboratories, to spot epidemics quickly and direct resources appropriately.

Monitoring local malaria transmission intensity is essential for planning evidence-based control strategies and evaluating their impact over time.,Anti-malarial antibodies provide information on cumulative exposure and have proven useful, in areas where transmission has dropped to low sustained levels, for retrospectively reconstructing the timing and magnitude of transmission reduction.,It is unclear whether serological markers are also informative in high transmission settings, where interventions may reduce transmission, but to a level where considerable exposure continues.,This study was conducted through ongoing KEMRI and CDC collaboration.,Asembo, in Western Kenya, is an area where intense malaria transmission was drastically reduced during a 1997-1999 community-randomized, controlled insecticide-treated net (ITN) trial.,Two approaches were taken to reconstruct malaria transmission history during the period from 1994 to 2009.,First, point measurements were calculated for seroprevalence, mean antibody titre, and seroconversion rate (SCR) against three Plasmodium falciparum antigens (AMA-1, MSP-119, and CSP) at five time points for comparison against traditional malaria indices (parasite prevalence and entomological inoculation rate).,Second, within individual post-ITN years, age-stratified seroprevalence data were analysed retrospectively for an abrupt drop in SCR by fitting alternative reversible catalytic conversion models that allowed for change in SCR.,Generally, point measurements of seroprevalence, antibody titres and SCR produced consistent patterns indicating that a gradual but substantial drop in malaria transmission (46-70%) occurred from 1994 to 2007, followed by a marginal increase beginning in 2008 or 2009.,In particular, proportionate changes in seroprevalence and SCR point estimates (relative to 1994 baseline values) for AMA-1 and CSP, but not MSP-119, correlated closely with trends in parasite prevalence throughout the entire 15-year study period.,However, retrospective analyses using datasets from 2007, 2008 and 2009 failed to detect any abrupt drop in transmission coinciding with the timing of the 1997-1999 ITN trial.,In this highly endemic area, serological markers were useful for generating accurate point estimates of malaria transmission intensity, but not for retrospective analysis of historical changes.,Further investigation, including exploration of different malaria antigens and/or alternative models of population seroconversion, may yield serological tools that are more informative in high transmission settings.,The online version of this article (doi:10.1186/1475-2875-13-451) contains supplementary material, which is available to authorized users.

Antibodies constitute a critical component of the naturally acquired immunity that develops following frequent exposure to malaria.,However, specific antibody titres have been reported to decline rapidly in the absence of reinfection, supporting the widely perceived notion that malaria infections fail to induce durable immunological memory responses.,Currently, direct evidence for the presence or absence of immune memory to malaria is limited.,In this study, we analysed the longevity of both antibody and B cell memory responses to malaria antigens among individuals who were living in an area of extremely low malaria transmission in northern Thailand, and who were known either to be malaria naïve or to have had a documented clinical attack of P. falciparum and/or P. vivax in the past 6 years.,We found that exposure to malaria results in the generation of relatively avid antigen-specific antibodies and the establishment of populations of antigen-specific memory B cells in a significant proportion of malaria-exposed individuals.,Both antibody and memory B cell responses to malaria antigens were stably maintained over time in the absence of reinfection.,In a number of cases where antigen-specific antibodies were not detected in plasma, stable frequencies of antigen-specific memory B cells were nonetheless observed, suggesting that circulating memory B cells may be maintained independently of long-lived plasma cells.,We conclude that infrequent malaria infections are capable of inducing long-lived antibody and memory B cell responses.

Elimination of urogenital schistosomiasis transmission is a priority for the Zanzibar Ministry of Health.,Preventative chemotherapy together with additional control interventions have successfully alleviated much of the disease burden.,However, a persistently high Schistosoma haematobium prevalence is found in certain areas.,Our aim was to characterise and evaluate these persistent “hot-spots” of transmission and reinfection in comparison with low-prevalence areas, to support the intervention planning for schistosomiasis elimination in Zanzibar.,Prevalences of S. haematobium were annually determined by a single urine filtration in schoolchildren from 45 administrative areas (shehias) in Unguja in 2012, 2013 and 2014.,Coverage data for biannual treatment with praziquantel were available from ministerial databases and internal surveys.,Among the 45 shehias, five hot-spot (≥ 15 % prevalence) and two low-prevalence (≤ 5 %) shehias were identified and surveyed in mid-2014.,Human-water contact sites (HWCSs) and the presence of S. haematobium-infected and uninfected Bulinus globosus, as well as safe water sources (SWSs) and their reliability in terms of water availability were determined and mapped.,We found no major difference in the treatment coverage between persistent hot-spot and low-prevalence shehias.,On average, there were considerably more HWCSs containing B. globosus in hot-spot than in low-prevalence shehias (n = 8 vs n = 2) and also more HWCSs containing infected B. globosus (n = 2 vs n = 0).,There was no striking difference in the average abundance of SWSs in hot-spot and low-prevalence shehias (n = 45 vs n = 38) and also no difference when considering SWSs with a constant water supply (average: 62 % vs 62 %).,The average number of taps with a constant water supply, however, was lower in hot-spot shehias (n = 7 vs n = 14).,Average distances from schools to the nearest HWCS were considerably shorter in hot-spot shehias (n = 229 m vs n = 722 m).,The number of HWCSs, their infestation with B. globosus and their distance to schools seem to play a major role for a persistently high S. haematobium prevalence in children.,In addition to treatment, increasing access to reliably working taps, targeted snail control at HWCSs near schools and enhanced behaviour change measures are needed to reduce prevalences in hot-spot areas and to finally reach elimination.,ISRCTN48837681.,The online version of this article (doi:10.1186/s13071-016-1847-0) contains supplementary material, which is available to authorized users.

Biannual mass drug administration (MDA) with praziquantel and additional interventions to eliminate urogenital schistosomiasis has been implemented on the Zanzibar islands, United Republic of Tanzania, since 2012.,We aimed to assess the coverage of school-based treatment (SBT) and community-wide treatment (CWT), to validate the coverage reported by the Zanzibar Ministry of Health (MoH) and to identify reasons for non-compliance.,We conducted a post-MDA cross-sectional survey in 93 schools and 92 communities on Pemba and Unguja islands in early 2014, 3-5 months after the last MDA round.,Pupils and adults were asked whether they had received and taken the praziquantel treatment provided in the last SBT or CWT, respectively, and the observed and reported coverage were compared.,Reasons for non-compliance were recorded in a pretested questionnaire and assessed in qualitative interviews.,Urine samples of participants were examined for Schistosoma haematobium eggs with a single urine filtration.,Around 8000 pupils and 4000 adults were included in the analysis.,Our survey revealed a SBT coverage of 85.2 % in Pemba and of 86.9 % in Unguja, which was in line with MoH reports from Pemba (84.3 %) and higher than reports from Unguja (63.9 %).,However, 15 among the 48 schools surveyed in Unguja had not received SBT.,Among the interviewed adults, 53.6 % in Pemba and 64.9 % in Unguja had received praziquantel during CWT, which was less than the 59.0 % and 67.7 %, respectively, indicated by MoH reports.,Moreover, only 43.8 % and 54.0 % of adults in Pemba and Unguja, respectively, had taken all the tablets as recommended.,The main reasons for not receiving or taking praziquantel were absence during CWT, no drug distributor coming, being busy, fear of adverse events, pregnancy, breastfeeding or feeling healthy.,To increase coverage and compliance in Zanzibar, SBT should target all schools and mobilization, sensitization and implementation of the CWT need to be improved.,To reach elimination of urogenital schistosomiasis transmission in Zanzibar and elsewhere, a very high treatment coverage and compliance at national and local level is key and additional control measures such as snail control and behaviour change interventions will need to be implemented area wide.,ISRCTN48837681.

In Chad, several species of tsetse flies (Genus: Glossina) transmit African animal trypanosomoses (AAT), which represents a major obstacle to cattle rearing, and sleeping sickness, which impacts public health.,After the failure of past interventions to eradicate tsetse, the government of Chad is now looking for other approaches that integrate cost-effective intervention techniques, which can be applied by the stake holders to control tsetse-transmitted trypanosomoses in a sustainable manner.,The present study thus attempted to assess the efficacy of restricted application of insecticides to cattle leg extremities using footbaths for controlling Glossina m. submorsitans, G. tachinoides and G. f. fuscipes in southern Chad.,Two sites were included, one close to the historical human African trypanosomiasis (HAT) focus of Moundou and the other to the active foci of Bodo and Moissala.,At both sites, a treated and an untreated herd were compared.,In the treatment sites, cattle were treated on a regular basis using a formulation of deltamethrin 0.005% (67 to 98 cattle were treated in one of the sites and 88 to 102 in the other one).,For each herd, tsetse densities were monthly monitored using 7 biconical traps set along the river and beside the cattle pen from February to December 2009.,The impact of footbath treatment on tsetse populations was strong (p < 10-3) with a reduction of 80% in total tsetse catches by the end of the 6-month footbath treatment.,The impact of footbath treatment as a vector control tool within an integrated strategy to manage AAT and HAT is discussed in the framework of the “One Health” concept.,Like other techniques based on the treatment of cattle, this technology should be used under controlled conditions, in order to avoid the development of insecticide and acaricide resistance in tsetse and tick populations, respectively.

An integrated strategy of intervention against tsetse flies was implemented in the Upper West Region of Ghana (9.62°-11.00° N, 1.40°-2.76° W), covering an area of ≈18,000 km2 within the framework of the Pan-African Tsetse and Trypanosomosis Eradication Campaign.,Two species were targeted: Glossina tachinoides and Glossina palpalis gambiensis.,The objectives were to test the potentiality of the sequential aerosol technique (SAT) to eliminate riverine tsetse species in a challenging subsection (dense tree canopy and high tsetse densities) of the total sprayed area (6,745 km2) and the subsequent efficacy of an integrated strategy including ground spraying (≈100 km2), insecticide treated targets (20,000) and insecticide treated cattle (45,000) in sustaining the results of tsetse suppression in the whole intervention area.,The aerial application of low-dosage deltamethrin aerosols (0.33-0.35 g a.i/ha) was conducted along the three main rivers using five custom designed fixed-wings Turbo thrush aircraft.,The impact of SAT on tsetse densities was monitored using 30 biconical traps deployed from two weeks before until two weeks after the operations.,Results of the SAT monitoring indicated an overall reduction rate of 98% (from a pre-intervention mean apparent density per trap per day (ADT) of 16.7 to 0.3 at the end of the fourth and last cycle).,One year after the SAT operations, a second survey using 200 biconical traps set in 20 sites during 3 weeks was conducted throughout the intervention area to measure the impact of the integrated control strategy.,Both target species were still detected, albeit at very low densities (ADT of 0.27 inside sprayed blocks and 0.10 outside sprayed blocks).,The SAT operations failed to achieve elimination in the monitored section, but the subsequent integrated strategy maintained high levels of suppression throughout the intervention area, which will contribute to improving animal health, increasing animal production and fostering food security.

Iron deficiency anemia (IDA) is a global public health problem among school age children, which retards psychomotor development and impairs cognitive performance.,There is limited data on prevalence and risk factors for IDA.,The aim of this study was to determine the prevalence, severity, and predictors of nutritional IDA in school age children in Southwest Ethiopia.,A community based cross-sectional study was conducted in Jimma Town, Southwest Ethiopia from April to July 2013.,A total of 616 school children aged 6 to 12 years were included in the study using multistage sampling technique.,A structured questionnaire was used to collect sociodemographic data.,Five milliliter venous blood was collected from each child for hematological examinations.,Anemia was defined as a hemoglobin level lower than 11.5 g/dl and 12 g/dl for age group of 5-11 years and 12-15 years, respectively.,Iron deficiency anemia was defined when serum iron and ferritin levels are below 10 µmol/l and 15 µg/dl, respectively.,Moreover, fresh stool specimen was collected for diagnosis of intestinal parasitic infection.,Stained thick and thin blood films were examined for detection of Plasmodium infection and study of red blood cell morphology.,Dietary patterns of the study subjects were assessed using food frequency questionnaire and anthropometric measurements were done.,Data were analyzed using SPSS V-20.0 for windows.,Overall, prevalence of anemia was 43.7%, and that of IDA was 37.4%.,Not-consuming protein source foods [AOR = 2.30, 95%CI(1.04,5.14)], not-consuming dairy products [AOR = 1.83, 95%CI(1.14,5.14)], not-consuming discretionary calories [AOR = 2.77, 95%CI(1.42,5.40)], low family income [AOR = 6.14, 95%CI(2.90,12.9)] and intestinal parasitic infections [AOR = 1.45, 95%CI(1.23, 5. 27)] were predictors of IDA.,Iron deficiency anemia is a moderate public health problem in the study site.,Dietary deficiencies and intestinal parasitic infections were predictors of IDA.,Therefore, emphasis should be given to the strategies for the prevention of risk factors for IDA.

Soil-transmitted helminths (STHs) are widespread in underdeveloped countries.,In Ethiopia, the prevalence and distribution of helminth infection varies by place and with age.,We therefore investigated the prevalence of and risk factors for STH infection in mothers and their one year-old children living in Butajira town and surrounding rural areas in southern Ethiopia.,In 2005-2006, 1065 pregnant women were recruited in their third trimester of pregnancy.,In 2006-2007, when children reached their first birthdays, data on the infants and their mothers were collected, including stool samples for qualitative STH analysis.,Questionnaire data on various demographic, housing and lifestyle variables were available.,Logistic regression analysis was employed to determine the independent risk factors for STH infection in the mothers and children.,908 mothers and 905 infants provided complete data for analysis.,Prevalence of any STH infection was 43.5% (95% confidence interval (CI) 40.2-46.8%) in mothers and 4.9% (95%CI 3.6-6.5%) in children.,In the fully adjusted regression model, infrequent use of soap by the mother was associated with increased risk (odds ratio (OR) 1.40, 95% CI 1.04-1.88, and 1.66, 95% CI 0.92-2.99, for use at least once a week and less frequent than once a week respectively, relative to daily use; p for trend = 0.018), and urban place of residence (OR 0.45, 95% CI 0.28-0.73, p = 0.001) was associated with reduced risk of maternal STH infection.,The only factor associated with STH infection in infants was household source of water, with the greatest risk in those using piped water inside the compound (OR 0.09, 95% CI 0.02-0.38 for river water, 0.20, 95% CI 0.56-0.69 for either well or stream water and 0.21, 95% CI 0.09-0.51 for piped water outside compared with piped water inside the compound, overall p = 0.002),In this rural Ethiopian community with a relatively high prevalence of STH infection, we found a reduced risk of infection in relation to maternal hygiene and urban living.,Daily use of soap and a safe supply of water are likely to reduce the risk of STH infection.

Trend analysis of malaria surveillance data is essential to inform stakeholders on progress towards malaria control.,From the total 387,096 cases of malaria reported in Amhara region in 2017, 167,079 (43.2%) cases were in Central, North and West Gondar zones.,From this total figure of zones, 15,445 (9.2%) were ≤ 5 years which contributes 4% of cases in the region.,So, the purpose of this study was to analyze trends of malaria parasite in Selected Zones of Amhara Region, Northwest Ethiopia.,A Retrospective study was conducted on purposely selected Central, North and West Gondar zones from July 1-30/ 2018.,Data were collected, entered, cleaned, analyzed and interpreted using Microsoft Excel-2010.,Different tables, figures and maps were used to present results.,A total of 2,827,722 cases have been received a diagnostic test of; Microscopy 1,712,193(60.56%) and Rapid Diagnostic Test (RDT) 1,115,529(39.44%).,Trends of total patients treated as confirmed and clinical malaria cases in July 2017-June 2018 were decreased to 139,297 (14%) as compared from July 2015-June 2016, 249,571(25%).,From total cases received diagnostic tests only 1,003,391 (36%) were confirmed and clinical cases treated with antimalaria.,Of these Plasmodium falciparum and vivax malaria cases were confirmed to be 1002,946 (99.96%) and clinical malaria cases were 445(0.04%), respectively.,Risk of infection and diagnostic effort were high in West Gondar Zone.,The Amhara public health institute including health Bureau, stakeholders and all responsible bodies should give special standing to highest malaria districts of West Gondar zone.

Transmission of malaria in the highlands of Ethiopia is poorly understood and usually attributed to importation by mobile populations or local transmission by Anopheles arabiensis.,To characterize and identify Anopheles species present in a highland area of northern Ethiopia, adult and larval collections were performed in Gondar town and the neighboring Senbet Debir village (Dembia district, > 2000 meters above sea level, masl), in addition to Bahir Dar town (capital of Amhara region) and Kumer Aftit village (Metema district, < 2000 masl).,CDC-light traps were used to collect adult mosquitoes and larval collections were performed from rain pools for rearing into adults for species identification.,Collections were made September-March 2016-2018.,Adult mosquitoes were identified morphologically and a subset of randomly chosen specimens were identified to species by sequencing the ribosomal DNA internal transcribed spacer region 2 (ITS2) and mitochondrial DNA cytochrome c oxidase subunit 1 (cox1).,The primary species of Anopheles identified at elevations higher than 2000 masl was An. cinereus, which was confirmed molecularly by ITS2 and cox1 sequencing.,Interestingly, two unknown species were also sequenced, in addition to two specimens of An. pretoriensis.,The species collected at sites with elevations less than 2000 masl (Bahir Dar town and Kumer Aftit village) was An. arabiensis.,Three Plasmodium falciparum-positive specimens were identified molecularly as An. cinereus.,The presence of Plasmodium-positive An. cinereus in areas greater than 2000 masl incriminates this species as a potential vector contributing to non-peak malaria transmission in Ethiopian highland areas.

Malaria transmission was reported to have declined in some East African countries.,However, a comparable trend has not been confirmed for West Africa.,This study aims to assess the dynamics of parasite prevalence and malaria species distribution over time in an area of highly seasonal transmission in Burkina Faso.,The aim was also to compare frequency of asymptomatic parasitaemia between wet and dry season by parasite density status and age group.,During the years 2009-2012, six cross-sectional studies were performed in the rural village Bourasso in the Nouna Health District in north-west Burkina Faso.,In subsequent rainy and dry seasons blood samples were collected to assess the parasite prevalence, species, density and clinical parameters.,In total, 1,767 children and adults were examined and compared to a baseline collected in 2000.,The microscopical parasite prevalence (mainly P. falciparum) measured over the rainy seasons decreased significantly from 78.9% (2000) to 58.4%, 55.9% and 49.3%, respectively (2009-2011; p <0.001).,The frequency of Plasmodium malariae infections (mono- and co-infections) decreased parallel to the overall parasite prevalence from 13.4% in 2000 to 2.1%, 4.1% and 4.7% in 2009-2011 (p <0.001).,Comparing parasite-positive subjects from the rainy season versus dry season, the risk of fever was significantly reduced in the dry season adjusting for parasite density (grouped) and age group.,The results of this study suggest a decline of malaria transmission over the rainy seasons between 2000 and 2009-2011 in the region of Nouna, Burkina Faso.,The decreased transmission intensity was associated with lower prevalence of P. malariae infections (both mono-infections and co-infections).,Asymptomatic parasitaemia was more frequent in the dry season even adjusting for parasite density and age group in a multivariate regression.,Possible reasons for this observation include the existence of less pathogenic Plasmodium falciparum genotypes prevailing in the dry season, or the effect of a reduced incidence density during the dry season.

Despite continuous efforts by the government and private sectors, malaria is still a public health problem in rural Peninsular Malaysia.,This study investigated household knowledge, attitude and practices (KAP) regarding malaria in two malaria endemic communities, forest-aboriginal and rural communities, in the Lipis district of Pahang state, Malaysia.,A descriptive cross-sectional study with a semi-structured questionnaire was carried out among 100 and 123 households from forest-aboriginal and rural areas, respectively.,Knowledge about malaria and its transmission is significantly higher among the rural participants than the aborigines (86.2% vs 76%, p < 0.01).,However, use of medicinal plants and beliefs in witchcraft and sorcery in treating febrile diseases were significantly higher among the aboriginal population (p < 0.01).,There were no significant differences between the two communities in terms of the knowledge about malaria symptoms, attitudes towards its severity and practices in preventive measures against malaria by using mosquito bed nets.,However, the knowledge and practice of different preventive measures to combat malaria, such as insecticide and the elimination of breeding areas, was significantly higher among the rural population than the aborigines (p < 0.001).,Both communities were aware of malaria as a disease, but knowledge, attitudes and practices were inadequate.,Providing efficient health education to people residing in malaria endemic areas would improve their understanding about malaria prevention in order to bring about the elimination of malaria from the country.

Primaquine is the only licensed drug for eradicating Plasmodium vivax hypnozoites and, therefore, preventing relapses of vivax malaria.,It is a vital component of global malaria elimination efforts.,Primaquine is efficacious when supervised in clinical trials, but its effectiveness in real-world settings is unknown.,We aimed to determine whether unsupervised primaquine was effective for preventing re-presentation to hospital with vivax malaria in southern Papua, Indonesia.,Routinely-collected hospital surveillance data were used to undertake a pragmatic comparison of the risk of re-presentation to hospital with vivax malaria in patients prescribed dihydroartemisinin-piperaquine (DHP) combined with primaquine versus those patients prescribed DHP alone.,The omission of primaquine was predominantly due to 3 stock outages.,Individual clinical, pharmacy, and laboratory data were merged using individual hospital identification numbers and the date of presentation to hospital.,Between April 2004 and December 2013, there were 86,797 documented episodes of vivax malaria, of which 62,492 (72.0%) were included in the analysis.,The risk of re-presentation with vivax malaria within 1 year was 33.8% (95% confidence Interval [CI] 33.1%-34.5%) after initial monoinfection with P. vivax and 29.2% (95% CI 28.1%-30.4%) after mixed-species infection.,The risk of re-presentation with P. vivax malaria was higher in children 1 to <5 years of age (49.6% [95% CI 48.4%-50.9%]) compared to patients 15 years of age or older (24.2% [95% CI 23.4-24.9%]); Adjusted Hazard Ratio (AHR) = 2.23 (95% CI 2.15-2.31), p < 0.001.,Overall, the risk of re-presentation was 37.2% (95% CI 35.6%-38.8%) in patients who were prescribed no primaquine compared to 31.6% (95% CI 30.9%-32.3%) in those prescribed either a low (≥1.5 mg/kg and <5 mg/kg) or high (≥5 mg/kg) dose of primaquine (AHR = 0.90 [95% CI 0.86-0.95, p < 0.001]).,Limiting the comparison to high dose versus no primaquine in the period during and 12 months before and after a large stock outage resulted in minimal change in the estimated clinical effectiveness of primaquine (AHR 0.91, 95% CI 0.85-0.97, p = 0.003).,Our pragmatic study avoided the clinical influences associated with prospective study involvement but was subject to attrition bias caused by passive follow-up.,Unsupervised primaquine for vivax malaria, prescribed according to the current World Health Organization guidelines, was associated with a minimal reduction in the risk of clinical recurrence within 1 year in Papua, Indonesia.,New strategies for the effective radical cure of vivax malaria are needed in resource-poor settings.,In a pragmatic hospital-based cohort study, Ric Price and colleagues compared risk of re-presentation with vivax malaria in patients prescribed dihydroartemisinin-piperaquine combined with primaquine versus patients who could not be given primaquine due to stock outages.

The diagnosis and treatment of Plasmodium vivax malaria differs from that of Plasmodium falciparum malaria in fundamentally important ways.,This article reviews the guiding principles, practices, and evidence underpinning the diagnosis and treatment of P. vivax malaria.

The surveillance of malaria is generally undertaken on the assumption that samples passively collected at health facilities are comparable to or representative of the broader Plasmodium reservoir circulating in the community.,Further characterization and comparability of the hidden asymptomatic parasite reservoir are needed to inform on the potential impact of sampling bias.,This study explores the impact of sampling strategy on molecular surveillance by comparing the genetic make-up of Plasmodium falciparum and Plasmodium vivax isolates collected by passive versus active case detection.,Sympatric isolates of P. falciparum and P. vivax were collected from a large community survey and ongoing clinical surveillance studies undertaken in the hypomesoendemic setting of Mimika District (Papua, Indonesia).,Plasmodium falciparum isolates were genotyped at nine microsatellite loci and P. vivax at eight loci.,Measures of diversity and differentiation were used to compare different patient and parasitological sample groups.,The results demonstrated that passively detected cases (symptomatic) had comparable population diversity to those circulating in the community (asymptomatic) in both species.,In addition, asymptomatic patent infections were as diverse as subpatent infections.,However, a significant difference in multiplicity of infection (MOI) and percentage of polyclonal infections was observed between actively and passively detected P. vivax cases (mean MOI: 1.7 ± 0.7 versus 1.4 ± 1.4, respectively; P = 0.001).,The study findings infer that, in hypomesoendemic settings, passive sampling is appropriate for molecular parasite surveillance strategies using the predominant clone in any given infection; however, the findings suggest caution when analyzing complexity of infection.,Further evaluation is required in other endemic settings.

Plasmodium vivax shows a small prevalence in West and Central Africa due to the high prevalence of Duffy negative people.,However, Duffy negative individuals infected with P. vivax have been reported in areas of high prevalence of Duffy positive people who may serve as supply of P. vivax strains able to invade Duffy negative erythrocytes.,We investigated the presence of P. vivax in two West African countries, using blood samples and mosquitoes collected during two on-going studies.,Blood samples from a total of 995 individuals were collected in seven villages in Angola and Equatorial Guinea, and 820 Anopheles mosquitoes were collected in Equatorial Guinea.,Identification of the Plasmodium species was achieved by nested PCR amplification of the small-subunit rRNA genes; P. vivax was further characterized by csp gene analysis.,Positive P. vivax-human isolates were genotyped for the Duffy blood group through the analysis of the DARC gene.,Fifteen Duffy-negative individuals, 8 from Equatorial Guinea (out of 97) and 7 from Angola (out of 898), were infected with two different strains of P. vivax (VK210 and VK247).,In this study we demonstrated that P. vivax infections were found both in humans and mosquitoes, which means that active transmission is occurring.,Given the high prevalence of infection in mosquitoes, we may speculate that this hypnozoite-forming species at liver may not be detected by the peripheral blood samples analysis.,Also, this is the first report of Duffy negative individuals infected with two different strains of P. vivax (VK247 and classic strains) in Angola and Equatorial Guinea.,This finding reinforces the idea that this parasite is able to use receptors other than Duffy to invade erythrocytes, which may have an enormous impact in P. vivax current distribution.

Parasitic diseases, such as sleeping sickness, Chagas disease and malaria, remain a major cause of morbidity and mortality worldwide, but particularly in tropical, developing countries.,Controlling these diseases requires a better understanding of host-parasite interactions, including a deep appreciation of parasite distribution in the host.,The preferred accumulation of parasites in some tissues of the host has been known for many years, but recent technical advances have allowed a more systematic analysis and quantifications of such tissue tropisms.,The functional consequences of tissue tropism remain poorly studied, although it has been associated with important aspects of disease, including transmission enhancement, treatment failure, relapse and clinical outcome.,Here, we discuss current knowledge of tissue tropism in Trypanosoma infections in mammals, describe potential mechanisms of tissue entry, comparatively discuss relevant findings from other parasitology fields where tissue tropism has been extensively investigated, and reflect on new questions raised by recent discoveries and their potential impact on clinical treatment and disease control strategies.

Malaria infection starts with injection of Plasmodium sporozoites by an Anopheles mosquito into the skin of the mammalian host.,How sporozoites locate and enter a blood vessel is a critical, but poorly understood process.,In this study, we examine sporozoite motility and their interaction with dermal blood vessels, using intravital microscopy in mice.,Our data suggest that sporozoites exhibit two types of motility: in regions far from blood vessels, they exhibit ‘avascular motility’, defined by high speed and less confinement, while in the vicinity of blood vessels their motility is more constrained.,We find that curvature of sporozoite tracks engaging with vasculature optimizes contact with dermal capillaries.,Imaging of sporozoites with mutations in key adhesive proteins highlight the importance of the sporozoite's gliding speed and its ability to modulate adhesive properties for successful exit from the inoculation site.,DOI:http://dx.doi.org/10.7554/eLife.07789.001,Malaria remains a devastating disease in many parts of the world.,Malaria parasites enter the host via the skin, where they are deposited by infected mosquitoes as they look for blood.,The parasites must exit the skin to reach the liver, where they multiply and ultimately infect red blood cells, where they cause the symptoms of the disease.,In the skin, the parasites must move to find blood vessels that they enter to travel via the blood circulation to the liver.,Only about 10-20% of parasites make it out of the skin, making this a bottleneck for the parasite.,Scientists have been working to develop vaccines that would protect people against malaria.,One way these could work would be to stop malaria parasites from leaving the skin and entering the blood vessels.,But to do that, more needs to be learnt about how the parasites move in the skin and enter the blood vessels.,Hopp et al., using a mouse model of malaria, created malaria parasites that produce a fluorescent protein that allows the parasites to be tracked after they have been injected into the skin of a mouse's ear.,This revealed that the parasites have two ways of moving.,After first being injected, the parasites move quickly and freely.,The parasites slow down when they come close to a blood vessel and move on or around the vessel for some time before entering it.,During this stage of movement, the parasites tend to move in paths that follow the curvature of the blood vessels, which may improve how well they make contact with the blood vessel surface and may enable them to find the areas of the vessels best suited for entry.,Next, Hopp et al. investigated how two parasite mutants move through mouse skin.,Both mutants had previously been found to be less likely than wild-type parasites to exit the inoculation site.,Hopp et al. found that one of the mutants moves slowly after being injected and so explores a smaller tissue volume than normal and encounters fewer blood vessels.,The second mutant parasite spends more time than normal moving on the surface of the blood vessels, but finds it difficult to enter them.,Continuing this work will allow us to learn more about the interactions between the parasite and the blood vessels, which in turn could reveal key events that could be targeted by a vaccine.,Furthermore, the significant amount of time that the parasites spend moving and looking for blood vessels in the skin could be a good time to target them with antibodies and prevent malaria infection.,DOI:http://dx.doi.org/10.7554/eLife.07789.002

Global malaria has been on the decline over the past decade due to expansion of interventions.,The present study aimed at determining the current status of malaria epidemiology in the context of sustained interventions and seasonal variations in Bolifamba, which represents a typical semi-urban malaria endemic community in the Cameroonian rainforest.,A monthly cross-sectional survey was carried out in Bolifamba, a multi ethnic semi-urban locality on the eastern flanks of Mt Cameroon, for a year during which blood samples were collected from participants and examined for malaria parasites by microscopy.,Correlation analysis of seasonal/monthly malaria prevalence was done with weather data from Ekona, a nearby village with a meteorological station.,Intervention strategy such as use of Insecticide Treated Bed Net (ITBN) and risk factors such as duration of stay in the locality, age and housing type were also investigated.,The results revealed a malaria prevalence of 38.3 % in the rainy season, which was significantly higher than 24.4 % observed in the dry season (P < 0.0001).,A high prevalence of asymptomatic malaria which was more than double the prevalence of symptomatic malaria on a monthly basis was observed, 30.7 % vs 17.8 % in the rainy and dry season respectively (p < 0.0001) and asymptomatic malaria was significantly associated with anemia (p < 0.005).,April was the peak month of malaria prevalence and coincided with peak periods of both asymptomatic and symptomatic malaria.,The Plasmodium falciparum parasite rates in the 2- up to 10-years age group (PfPR(2-10)) was 40.8 %.,The regular use of ITBN was significantly associated with low prevalence of 31.7 % as opposed to irregular or non-usage of ITBN 38.2 % (p < 0.05).,Log of parasite load was found to initially increase to 2.49 with less than 5 years of stay, and decreased gradually with increasing duration of stay in the locality (p = 0.046).,Climatic factors were significantly and positively associated with monthly malaria prevalence and the strongest predictors of malaria prevalence were rainfall and minimum temperature with r values of 0.563 and 0.6 respectively.,The study highlights the role of seasonal change in modifying malaria prevalence during the year and the beneficial effect of ITBN.,It also underscores a sublime problem of asymptomatic malaria associated with anemia, and indicates that partial immunity is acquired with prolonged stay in Bolifamba.,This preliminary result is the basis of ongoing work to identify the antigens involved in acquired immunity.

Haematologic abnormalities are features in Plasmodium falciparum infection, and anaemia is an inevitable outcome.,This study examines the influence of malaria status and altitude on haematologic parameters in school-aged pupils.,A cross-sectional study was conducted among 728 school pupils aged between four and 15 years at three different altitudinal ranges along the slope of the Mount Cameroon region.,The investigative methods included the use of questionnaire, clinical evaluation and laboratory investigations.,Blood sample collected from each child was used for the preparation of blood films for detection of malaria parasites and assessment of malaria parasite density as well as full blood count determination using an automated haematology analyzer.,The prevalence of malaria in the study population was 33.8% and 64.2% (158/246) of these were asymptomatic (AM).,Pupils in lowlands had a significantly (P <0.05) prevalence (95% confidence interval, CI) of malaria (60.6%, CI = 54.6-65.9%) than those in middle belt (29.1%, CI = 23.9-34.8%) and highlands (7.7%, CI = 6.1-9.8%), while those in middle belt had significantly higher geometric mean parasite density (475) than those in lowlands (233) and highlands (388).,The prevalence of malaria was significantly higher in children that presented with fever (40.4%, CI = 33.8-47.2%) when compared with afebrile subjects (31%, CI = 27-35.2%).,Pupils with AM had a higher prevalence of leucopaenia (43.7%, CI = 35.8-51.8%), microcytosis (27.2%, CI = 20.5-34.9%), hypochromasia (27.8%, CI = 21-35.5%) and thrombocytopaenia (14.9%, CI = 8.9-22.8%) when compared with those with clinical malaria (CM).,All mean haematological parameters were comparable in pupils with CM and AM, except for the mean white blood cell (WBC) counts.,Pupils with AM had significantly lower (P = 0.02) mean WBC counts (5.1 ± 2.5 × 109/L) than those with CM (5.9 ± 2.3 × 109/L).,Age, altitude and malaria parasitaemia was of significant influence on several haematological parameters.,Altitude influenced the distribution and density of malaria parasites and was of confounding influence on the haematologic profiles.,These results highlight the insidious effects of AM on the haematologic components.

Malaria morbidity and mortality has declined in recent years in a number of settings.,The ability to describe changes in malaria transmission associated with these declines is important in terms of assessing the potential effects of control interventions, and for monitoring and evaluation purposes.,Data from five cross-sectional surveys conducted in Farafenni and surrounding villages on the north bank of River Gambia between 1988 and 2011 were compiled.,Antibody responses to MSP-119 were measured in samples from all surveys, data were normalized and expressed as seroprevalence and seroconversion rates (SCR) using different mathematical models.,Results showed declines in serological metrics with seroprevalence in children aged one to 5 years dropping from 19 % (95 % CI 15-23 %) in 1988 to 1 % (0-2 %) in 2011 (p value for trend in proportions < 0.001) and the SCR dropping from 0.069 year−1 (0.059-0.080) to 0.022 year−1 (0.017-0.028; p = 0.004).,The serological data were consistent with previously described drops in both parasite prevalence in children aged 1-5 years (62 %, 57-66 %, in 1988 to 2 %, 0-4 %, in 2011; p < 0.001), and all-cause under five mortality rates (37 per 1000 person-years, 34-41, in 1990 to 17, 15-19, in 2006; p = 0.059).,This analysis shows accurate reconstruction of historical malaria transmission patterns in the Farafenni area using anti-malarial antibody responses.,Demonstrating congruence between serological measures, and conventional clinical and parasitological measures suggests broader utility for serology in monitoring and evaluation of malaria transmission.,The online version of this article (doi:10.1186/s12936-015-0939-1) contains supplementary material, which is available to authorized users.

Antibodies constitute a critical component of the naturally acquired immunity that develops following frequent exposure to malaria.,However, specific antibody titres have been reported to decline rapidly in the absence of reinfection, supporting the widely perceived notion that malaria infections fail to induce durable immunological memory responses.,Currently, direct evidence for the presence or absence of immune memory to malaria is limited.,In this study, we analysed the longevity of both antibody and B cell memory responses to malaria antigens among individuals who were living in an area of extremely low malaria transmission in northern Thailand, and who were known either to be malaria naïve or to have had a documented clinical attack of P. falciparum and/or P. vivax in the past 6 years.,We found that exposure to malaria results in the generation of relatively avid antigen-specific antibodies and the establishment of populations of antigen-specific memory B cells in a significant proportion of malaria-exposed individuals.,Both antibody and memory B cell responses to malaria antigens were stably maintained over time in the absence of reinfection.,In a number of cases where antigen-specific antibodies were not detected in plasma, stable frequencies of antigen-specific memory B cells were nonetheless observed, suggesting that circulating memory B cells may be maintained independently of long-lived plasma cells.,We conclude that infrequent malaria infections are capable of inducing long-lived antibody and memory B cell responses.

BRAC, an indigenous non-governmental development organization (NGO), has been implementing a programme to prevent and control malaria in the 13 malaria-endemic districts of Bangladesh since 2007.,One of the critical preventive interventions is the distribution of insecticidal bed nets (long-lasting insecticide-treated nets, LLINs and insecticide-treated ordinary nets, ITNs) to the community free of cost.,This study aimed to assess progress in the possession, preferential use, and knowledge on use of the LLIN/ITNs including the programme's avowed pro-poor inclination one and three and half years after intervention began.,A convenient sampling strategy based on malaria endemicity in the districts was adopted.,First, thirty upazila (sub-district, with a population around 250,000)s were selected at random, with high prevalent districts contributing more upazilas; second, from each upazila, one (2008) to two (2011) villages (covered by insecticidal bed net distribution programme) were selected.,From each village, households that had either one under-five child and/or a pregnant woman were included in the survey, one household being included only once.,Data were collected using a pre-tested structured questionnaire.,In all, 3,760 households in 2008 and 7,895 households in 2011 were surveyed for collecting relevant information.,Proportion of households with at least one LLIN, and at least one LLIN/ITN increased (22-59 to 62-67% and 22-64% to 74-76% respectively) over time, including increase in the mean number of LLIN/ITNs per household (≤ 1 to 1 +).,The programme achieved > 80% coverage in sleeping under an LLIN/ITN in the case of under-five children and pregnant women, especially in the high-endemic districts.,Knowledge regarding critical time of hanging the net also increased over time (7-22 to 44-54%), but remained low.,The pro-poor inclination of the programme is reflected in the status of relevant indicators according to self-rated poverty status of the households.,There has been a substantial improvement in possession and usage of insecticidal bed nets especially for the two most vulnerable groups (under-five children and pregnant women), including a reduction of gaps between the high and low endemic districts, and the deficit and non-deficit households during the study period.

Malaria, caused by the parasite Plasmodium falciparum, is a significant source of morbidity and mortality in southern Zambia.,In the Mapanza Chiefdom, where transmission is seasonal, Anopheles arabiensis is the dominant malaria vector.,The ability to predict larval habitats can help focus control measures.,A survey was conducted in March-April 2007, at the end of the rainy season, to identify and map locations of water pooling and the occurrence anopheline larval habitats; this was repeated in October 2007 at the end of the dry season and in March-April 2008 during the next rainy season.,Logistic regression and generalized linear mixed modeling were applied to assess the predictive value of terrain-based landscape indices along with LandSat imagery to identify aquatic habitats and, especially, those with anopheline mosquito larvae.,Approximately two hundred aquatic habitat sites were identified with 69 percent positive for anopheline mosquitoes.,Nine species of anopheline mosquitoes were identified, of which, 19% were An. arabiensis.,Terrain-based landscape indices combined with LandSat predicted sites with water, sites with anopheline mosquitoes and sites specifically with An. arabiensis.,These models were especially successful at ruling out potential locations, but had limited ability in predicting which anopheline species inhabited aquatic sites.,Terrain indices derived from 90 meter Shuttle Radar Topography Mission (SRTM) digital elevation data (DEM) were better at predicting water drainage patterns and characterizing the landscape than those derived from 30 m Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) DEM.,The low number of aquatic habitats available and the ability to locate the limited number of aquatic habitat locations for surveillance, especially those containing anopheline larvae, suggest that larval control maybe a cost-effective control measure in the fight against malaria in Zambia and other regions with seasonal transmission.,This work shows that, in areas of seasonal malaria transmission, incorporating terrain-based landscape models to the planning stages of vector control allows for the exclusion of significant portions of landscape that would be unsuitable for water to accumulate and for mosquito larvae occupation.,With increasing free availability of satellite imagery such as SRTM and LandSat, the development of satellite imagery-based prediction models is becoming more accessible to vector management coordinators.

Understanding the global limits of transmission of soil-transmitted helminth (STH) species is essential for quantifying the population at-risk and the burden of disease.,This paper aims to define these limits on the basis of environmental and socioeconomic factors, and additionally seeks to investigate the effects of urbanisation and economic development on STH transmission, and estimate numbers at-risk of infection with Ascaris lumbricoides, Trichuris trichiura and hookworm in 2010.,A total of 4,840 geo-referenced estimates of infection prevalence were abstracted from the Global Atlas of Helminth Infection and related to a range of environmental factors to delineate the biological limits of transmission.,The relationship between STH transmission and urbanisation and economic development was investigated using high resolution population surfaces and country-level socioeconomic indicators, respectively.,Based on the identified limits, the global population at risk of STH transmission in 2010 was estimated.,High and low land surface temperature and extremely arid environments were found to limit STH transmission, with differential limits identified for each species.,There was evidence that the prevalence of A. lumbricoides and of T. trichiura infection was statistically greater in peri-urban areas compared to urban and rural areas, whilst the prevalence of hookworm was highest in rural areas.,At national levels, no clear socioeconomic correlates of transmission were identified, with the exception that little or no infection was observed for countries with a per capita gross domestic product greater than US$ 20,000.,Globally in 2010, an estimated 5.3 billion people, including 1.0 billion school-aged children, lived in areas stable for transmission of at least one STH species, with 69% of these individuals living in Asia.,A further 143 million (31.1 million school-aged children) lived in areas of unstable transmission for at least one STH species.,These limits provide the most contemporary, plausible representation of the extent of STH risk globally, and provide an essential basis for estimating the global disease burden due to STH infection.

Albendazole and mebendazole are increasingly deployed for preventive chemotherapy targeting soil-transmitted helminth (STH) infections.,We assessed the efficacy of single oral doses of albendazole (400 mg) and mebendazole (500 mg) for the treatment of hookworm infection in school-aged children in Lao PDR.,Since Opisthorchis viverrini is co-endemic in our study setting, the effect of the two drugs could also be determined against this liver fluke.,We conducted a randomized, open-label, two-arm trial.,In total, 200 children infected with hookworm (determined by quadruplicate Kato-Katz thick smears derived from two stool samples) were randomly assigned to albendazole (n = 100) and mebendazole (n = 100).,Cure rate (CR; percentage of children who became egg-negative after treatment), and egg reduction rate (ERR; reduction in the geometric mean fecal egg count at treatment follow-up compared to baseline) at 21-23 days posttreatment were used as primary outcome measures.,Adverse events were monitored 3 hours post treatment.,Single-dose albendazole and mebendazole resulted in CRs of 36.0% and 17.6% (odds ratio: 0.4; 95% confidence interval: 0.2-0.8; P = 0.01), and ERRs of 86.7% and 76.3%, respectively.,In children co-infected with O. viverrini, albendazole and mebendazole showed low CRs (33.3% and 24.2%, respectively) and moderate ERRs (82.1% and 78.2%, respectively).,Both albendazole and mebendazole showed disappointing CRs against hookworm, but albendazole cured infection and reduced intensity of infection with a higher efficacy than mebendazole.,Single-dose administrations showed an effect against O. viverrini, and hence it will be interesting to monitor potential ancillary benefits of a preventive chemotherapy strategy that targets STHs in areas where opisthorchiasis is co-endemic.,Current Controlled Trials ISRCTN29126001

Clonally variant genes (CVGs) play fundamental roles in the adaptation of Plasmodium falciparum to fluctuating conditions of the human host.,However, their expression patterns under the natural conditions of the blood circulation have been characterized in detail for only a few specific gene families.,Here, we provide a detailed characterization of the complete P. falciparum transcriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in malaria-naive human volunteers.,We found that the vast majority of transcriptional differences between parasites obtained from the volunteers and the parental parasite line maintained in culture occurred in CVGs.,In particular, we observed a major increase in the transcript levels of most genes of the pfmc-2tm and gbp families and of specific genes of other families, such as phist, hyp10, rif, or stevor, in addition to previously reported changes in var and clag3 gene expression.,Increased transcript levels of individual pfmc-2tm, rif, and stevor genes involved activation in small subsets of parasites.,Large transcriptional differences correlated with changes in the distribution of heterochromatin, confirming their epigenetic nature.,Furthermore, the similar expression of several CVGs between parasites collected at different time points along the blood infection suggests that the epigenetic memory for multiple CVG families is lost during transmission stages, resulting in a reset of their transcriptional state.,Finally, the CVG expression patterns observed in a volunteer likely infected by a single sporozoite suggest that new epigenetic patterns are established during liver stages.

The lack of a continuous long-term in vitro culture system for Plasmodium vivax severely limits our knowledge of pathophysiology of the most widespread malaria parasite.,To gain direct understanding of P. vivax human infections, we used Next Generation Sequencing data mining to unravel parasite in vivo expression profiles for P. vivax, and P. falciparum as comparison.,We performed cloud and local computing to extract parasite transcriptomes from publicly available raw data of human blood samples.,We developed a Poisson Modelling (PM) method to confidently identify parasite derived transcripts in mixed RNAseq signals of infected host tissues.,We successfully retrieved and reconstructed parasite transcriptomes from infected patient blood as early as the first blood stage cycle; and the same methodology did not recover any significant signal from controls.,Surprisingly, these first generation blood parasites already show strong signature of transmission, which indicates the commitment from asexual-to-sexual stages.,Further, we place the results within the context of P. vivax’s complex life cycle, by developing mathematical models for P. vivax and P. falciparum and using sensitivity analysis assess the relative epidemiological impact of possible early stage transmission.,The study uncovers the earliest onset of P. vivax blood pathogenesis and highlights the challenges of P. vivax eradication programs.,The online version of this article (10.1186/s12918-018-0669-4) contains supplementary material, which is available to authorized users.

Stephen Lim and colleagues use several sources of data to estimate the changes in distribution of insecticide-treated bed nets across Africa between 2000 and 2008, and to analyze the link between development assistance and net coverage.,Development assistance for health (DAH) targeted at malaria has risen exponentially over the last 10 years, with a large fraction of these resources directed toward the distribution of insecticide-treated bed nets (ITNs).,Identifying countries that have been successful in scaling up ITN coverage and understanding the role of DAH is critical for making progress in countries where coverage remains low.,Sparse and inconsistent sources of data have prevented robust estimates of the coverage of ITNs over time.,We combined data from manufacturer reports of ITN deliveries to countries, National Malaria Control Program (NMCP) reports of ITNs distributed to health facilities and operational partners, and household survey data using Bayesian inference on a deterministic compartmental model of ITN distribution.,For 44 countries in Africa, we calculated (1) ITN ownership coverage, defined as the proportion of households that own at least one ITN, and (2) ITN use in children under 5 coverage, defined as the proportion of children under the age of 5 years who slept under an ITN.,Using regression, we examined the relationship between cumulative DAH targeted at malaria between 2000 and 2008 and the change in national-level ITN coverage over the same time period.,In 1999, assuming that all ITNs are owned and used in populations at risk of malaria, mean coverage of ITN ownership and use in children under 5 among populations at risk of malaria were 2.2% and 1.5%, respectively, and were uniformly low across all 44 countries.,In 2003, coverage of ITN ownership and use in children under 5 was 5.1% (95% uncertainty interval 4.6% to 5.7%) and 3.7% (2.9% to 4.9%); in 2006 it was 17.5% (16.4% to 18.8%) and 12.9% (10.8% to 15.4%); and by 2008 it was 32.8% (31.4% to 34.4%) and 26.6% (22.3% to 30.9%), respectively.,In 2008, four countries had ITN ownership coverage of 80% or greater; six countries were between 60% and 80%; nine countries were between 40% and 60%; 12 countries were between 20% and 40%; and 13 countries had coverage below 20%.,Excluding four outlier countries, each US$1 per capita in malaria DAH was associated with a significant increase in ITN household coverage and ITN use in children under 5 coverage of 5.3 percentage points (3.7 to 6.9) and 4.6 percentage points (2.5 to 6.7), respectively.,Rapid increases in ITN coverage have occurred in some of the poorest countries, but coverage remains low in large populations at risk.,DAH targeted at malaria can lead to improvements in ITN coverage; inadequate financing may be a reason for lack of progress in some countries.,Please see later in the article for the Editors' Summary,Malaria is a major global public-health problem.,Nearly half of the world's population is at risk of this parasitic disease, which kills about one million people (mainly children living in sub-Saharan Africa) every year.,Malaria is transmitted to people through the bites of infected night-flying mosquitoes.,Soon after entering the human body, the parasite begins to replicate in red blood cells, bursting out every 2-3 days and infecting more red blood cells.,The parasite's presence in the bloodstream causes malaria's characteristic fever and can cause fatal organ damage.,Malaria can be prevented by controlling the mosquitoes that spread the parasite and by sleeping under insecticide-treated bed nets (ITNs) to avoid mosquito bites.,In trials, ITN use reduced deaths in young children by about 20%.,Consequently, the widespread provision of ITNs is a mainstay of the World Health Organization's efforts to control malaria and in 2005 the World Assembly agreed to a target of providing ITNs for 80% of the people at risk of malaria by 2010.,Development assistance for health (DAH) targeted at malaria has increased considerably over the past decade.,Much of this resource has been directed toward increasing ITN coverage, but has it been used effectively?,To answer this question and to track progress toward universal ITN provision, reliable estimates of ITN coverage are critical.,Most attempts to quantify ITN coverage have relied on single sources of data such as manufacturers' records of ITNs supplied to individual countries, National Malaria Control Program reports on ITN distribution, or household surveys of ITN use.,Because each of these data sources has weaknesses, robust estimates of ITN coverage over time cannot be calculated from a single data source.,In this study, the researchers combine data from these three sources to calculate ITN ownership coverage (the proportion of households owning at least one ITN) and ITN use in children under 5 coverage (the proportion of children under the age of 5 years sleeping under an ITN) for 44 African countries between 1999 and 2008.,They also investigate the relationship between changes in ITN coverage and the cumulative DAH targeted for malaria for each country over this period.,The researchers combined the three sources of data by applying a statistical method called Bayesian inference to a “deterministic compartmental model” of ITN distribution, a flow chart that represents ITN movement into and within countries.,In 1999, the researchers estimate, ITN ownership and ITN use by young children were uniformly low across the 44 countries.,On average, only 2.2% of households owned ITNs and only 1.5% of young children slept under bed nets.,By 2008, 32.8% of households owned ITNs and 26.6% of young children slept under ITNs but there were now large differences in ITN coverage between countries.,In four countries, 80% or more of households owned an ITN but in 13 countries (including Nigeria), ITN ownership was below 20%.,Finally, the researchers used a statistical technique called regression to reveal that the estimated increase in national ITN coverage between 2000 and 2008 was strongly related to the cumulative national DAH targeted for malaria (calculated by identifying all the grants and loans provided for malaria control) over the same period.,The accuracy of these findings depends on the assumptions included in the model of ITN distribution and the quality of the data fed into it.,Nevertheless, this systematic analysis provides new insights into the progress of ITN provision in Africa and a robust way to monitor future ITN coverage.,Its findings show that several countries, even some very poor countries, have managed to scale up their ITN coverage from near zero to above 60%.,However, because countries such as Nigeria that have large populations at risk of malaria continue to have low ITN coverage, Africa as a whole falls far short of the target of 80% ITN coverage by 2010.,Finally, the clear relationship between the expansion of DAH targeted at malaria and increased ITN coverage suggests that inadequate funding may be responsible for the lack of progress in some countries and indicates that continued external financial assistance will be required to maintain the improvements in ITN coverage that have already been achieved.,Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000328.,Further information is available on the Institute for Health Metrics and Evaluation at the University of Washington,Information is available from the World Health Organization on malaria (in several languages); the 2009 World Malaria Report provides details of the current global malaria situation,The US Centers for Disease Control and Prevention provide information on malaria and on insecticide-treated bed nets (in English and Spanish),Information is available from the Roll Back Malaria Partnership on its approach to the global control of malaria including fact sheets on malaria in Africa and on insecticide-treated bed nets (in English, French and Portuguese),MedlinePlus provides links to additional information on malaria (in English and Spanish)

In 2005, a nationwide survey estimated that 6.5% of households in Ethiopia owned an insecticide-treated net (ITN), 17% of households had been sprayed with insecticide, and 4% of children under five years of age with a fever were taking an anti-malarial drug.,Similar to other sub-Saharan African countries scaling-up malaria interventions, the Government of Ethiopia set an ambitious national goal in 2005 to (i) provide 100% ITN coverage in malarious areas, with a mean of two ITNs per household; (ii) to scale-up indoor residual spraying of households with insecticide (IRS) to cover 30% of households targeted for IRS; and (iii) scale-up the provision of case management with rapid diagnostic tests (RDTs) and artemisinin-based combination therapy (ACT), particularly at the peripheral level.,A nationally representative malaria indicator survey (MIS) was conducted in Ethiopia between September and December 2007 to determine parasite and anaemia prevalence in the population at risk and to assess coverage, use and access to scaled-up malaria prevention and control interventions.,The survey used a two-stage random cluster sample of 7,621 households in 319 census enumeration areas.,A total of 32,380 people participated in the survey.,Data was collected using standardized Roll Back Malaria Monitoring and Evaluation Reference Group MIS household and women's questionnaires, which were adapted to the local context.,Data presented is for households in malarious areas, which according to the Ethiopian Federal Ministry of Health are defined as being located <2,000 m altitude.,Of 5,083 surveyed households, 3,282 (65.6%) owned at least one ITN.,In ITN-owning households, 53.2% of all persons had slept under an ITN the prior night, including 1,564/2,496 (60.1%) children <5 years of age, 1,891/3,009 (60.9%) of women 15 - 49 years of age, and 166/266 (65.7%) of pregnant women.,Overall, 906 (20.0%) households reported to have had IRS in the past 12 months.,Of 747 children with reported fever in the two weeks preceding the survey, 131 (16.3%) sought medical attention within 24 hours.,Of those with fever, 86 (11.9%) took an anti-malarial drug and 41 (4.7%) took it within 24 hours of fever onset.,Among 7,167 surveyed individuals of all ages, parasitaemia as estimated by microscopy was 1.0% (95% CI 0.5 - 1.5), with 0.7% and 0.3% due to Plasmodium falciparum and Plasmodium vivax, respectively.,Moderate-severe anaemia (haemoglobin <8 g/dl) was observed in 239/3,366 (6.6%, 95% CI 4.9-8.3) children <5 years of age.,Since mid-2005, the Ethiopian National Malaria Control Programme has considerably scaled-up its malaria prevention and control interventions, demonstrating the impact of strong political will and a committed partnership.,The MIS showed, however, that besides sustaining and expanding malaria intervention coverage, efforts will have to be made to increase intervention access and use.,With ongoing efforts to sustain and expand malaria intervention coverage, to increase intervention access and use, and with strong involvement of the community, Ethiopia expects to achieve its targets in terms of coverage and uptake of interventions in the coming years and move towards eliminating malaria.

Plasmodium falciparum malaria remains one of the most serious health problems globally and a protective malaria vaccine is desperately needed.,Vaccination with attenuated parasites elicits multiple cellular effector mechanisms that lead to Plasmodium liver stage elimination.,While granule-mediated cytotoxicity requires contact between CD8+ effector T cells and infected hepatocytes, cytokine secretion should allow parasite killing over longer distances.,To better understand the mechanism of parasite elimination in vivo, we monitored the dynamics of CD8+ T cells in the livers of naïve, immunized and sporozoite-infected mice by intravital microscopy.,We found that immunization of BALB/c mice with attenuated P. yoelii 17XNL sporozoites significantly increases the velocity of CD8+ T cells patrolling the hepatic microvasculature from 2.69±0.34 μm/min in naïve mice to 5.74±0.66 μm/min, 9.26±0.92 μm/min, and 7.11±0.73 μm/min in mice immunized with irradiated, early genetically attenuated (Pyuis4-deficient), and late genetically attenuated (Pyfabb/f-deficient) parasites, respectively.,Sporozoite infection of immunized mice revealed a 97% and 63% reduction in liver stage density and volume, respectively, compared to naïve controls.,To examine cellular mechanisms of immunity in situ, naïve mice were passively immunized with hepatic or splenic CD8+ T cells.,Unexpectedly, adoptive transfer rendered the motile CD8+ T cells from immunized mice immotile in the liver of P. yoelii infected mice.,Similarly, when mice were simultaneously inoculated with viable sporozoites and CD8+ T cells, velocities 18 h later were also significantly reduced to 0.68±0.10 μm/min, 1.53±0.22 μm/min, and 1.06±0.26 μm/min for CD8+ T cells from mice immunized with irradiated wild type sporozoites, Pyfabb/f-deficient parasites, and P. yoelii CS280-288 peptide, respectively.,Because immobilized CD8+ T cells are unable to make contact with infected hepatocytes, soluble mediators could potentially play a key role in parasite elimination under these experimental conditions.

Plasmodium falciparum malaria has been suspected to cause hearing loss.,Developmental, cognitive and language disorders have been observed in children, surviving cerebral malaria.,This prospective study aims to evaluate whether malaria influences hearing in mice.,Twenty mice were included in a standardized murine cerebral malaria model.,Auditory evoked brainstem responses were assessed before infection and at the peak of the illness.,A significant hearing impairment could be demonstrated in mice with malaria, especially the cerebral form.,The control group did not show any alterations.,No therapy was used.,This suggests that malaria itself leads to a hearing impairment in mice.

The dynamics of Plasmodium vivax infection is characterized by reactivation of hypnozoites at varying time intervals.,The relative contribution of new P. vivax infection and reactivation of dormant liver stage hypnozoites to initiation of blood stage infection is unclear.,In this study, we investigate the contribution of new inoculations of P. vivax sporozoites to primary infection versus reactivation of hypnozoites by modeling the dynamics of P. vivax infection in Thailand in patients receiving treatment for either blood stage infection alone (chloroquine), or the blood and liver stages of infection (chloroquine + primaquine).,In addition, we also analysed rates of infection in a study in Papua New Guinea (PNG) where patients were treated with either artesunate, or artesunate + primaquine.,Our results show that up to 96% of the P. vivax infection is due to hypnozoite reactivation in individuals living in endemic areas in Thailand.,Similar analysis revealed the around 70% of infections in the PNG cohort were due to hypnozoite reactivation.,We show how the age of the cohort, primaquine drug failure, and seasonality may affect estimates of the ratio of primary P. vivax infection to hypnozoite reactivation.,Modeling of P. vivax primary infection and hypnozoite reactivation provides important insights into infection dynamics, and suggests that 90-96% of blood stage infections arise from hypnozoite reactivation.,Major differences in infection kinetics between Thailand and PNG suggest the likelihood of drug failure in PNG.

Transmission intensity affects almost all aspects of malaria epidemiology and the impact of malaria on human populations.,Maps of transmission intensity are necessary to identify populations at different levels of risk and to evaluate objectively options for disease control.,To remain relevant operationally, such maps must be updated frequently.,Following the first global effort to map Plasmodium falciparum malaria endemicity in 2007, this paper describes the generation of a new world map for the year 2010.,This analysis is extended to provide the first global estimates of two other metrics of transmission intensity for P. falciparum that underpin contemporary questions in malaria control: the entomological inoculation rate (PfEIR) and the basic reproductive number (PfR).,Annual parasite incidence data for 13,449 administrative units in 43 endemic countries were sourced to define the spatial limits of P. falciparum transmission in 2010 and 22,212 P. falciparum parasite rate (PfPR) surveys were used in a model-based geostatistical (MBG) prediction to create a continuous contemporary surface of malaria endemicity within these limits.,A suite of transmission models were developed that link PfPR to PfEIR and PfR and these were fitted to field data.,These models were combined with the PfPR map to create new global predictions of PfEIR and PfR.,All output maps included measured uncertainty.,An estimated 1.13 and 1.44 billion people worldwide were at risk of unstable and stable P. falciparum malaria, respectively.,The majority of the endemic world was predicted with a median PfEIR of less than one and a median PfRc of less than two.,Values of either metric exceeding 10 were almost exclusive to Africa.,The uncertainty described in both PfEIR and PfR was substantial in regions of intense transmission.,The year 2010 has a particular significance as an evaluation milestone for malaria global health policy.,The maps presented here contribute to a rational basis for control and elimination decisions and can serve as a baseline assessment as the global health community looks ahead to the next series of milestones targeted at 2015.

Improved drug regimens are needed to accelerate elimination of lymphatic filariasis in Africa.,This study determined whether a single co-administered dose of ivermectin plus diethylcarbamazine plus albendazole [IDA] is noninferior to standard 3 annual doses of ivermectin plus albendazole (IA) used in many LF-endemic areas of Africa.,Treatment-naive adults with Wuchereria bancrofti microfilaremia in Côte d’Ivoire were randomized to receive a single dose of IDA (n = 43) or 3 annual doses of IA (n = 52) in an open-label, single-blinded trial.,The primary endpoint was the proportion of participants who were microfilaria (Mf) negative at 36 months.,Secondary endpoints were Mf clearance at 6, 12, and 24 months; inactivation of adult worm nests; and safety.,At 36 months posttreatment with IDA, 18/33 (55%; 95% CI, 38-72%) cleared Mf versus 33/42 (79%; 67-91%) with IA (P = .045).,At 6 and 12 months IDA was superior to IA in clearing Mf (89% [77-99%] and 71% [56-85%]), respectively, versus 34% (20-48%) and 26% (14-42%) (P < .001).,IDA was equivalent to IA at 24 months (61% [45-77%] vs 54% [38-72%]; P = .53).,IDA was superior to IA for inactivating adult worms at all time points.,Both treatments were well tolerated, and there were no serious adverse events.,A single dose of IDA was superior to 2 doses of IA in reducing the overall Mf burden by 24 months.,Reinfection may have contributed to the lack of sustained clearance of Mf with IDA.,NCT02974049.,A single dose of ivermectin, diethylcarbamazine, and albendazole is superior to standard treatment with ivermectin and albendazole for microfilarial clearance at 6 and 12 months and equivalent to 2 annual doses of ivermectin and albendazole at 24 months.

Antibody (Ab) to the Wuchereria bancrofti (Wb) infective larval (L3) antigen Wb123, using a Luciferase Immunoprecipitation System (LIPS) assay, has been shown to be a species-specific, early marker of infection developed for potential use as a surveillance tool following transmission interruption post mass drug administration.,To examine its usefulness in a single filarial-endemic island assessed at two time points with markedly different levels of transmission, Ab to Wb123 was measured in sera collected from subjects from Mauke, Cook Islands in 1975 (no previous treatment) and 1992 (5 years after a one time island-wide treatment with diethylcarbamazine [DEC]).,Between 1975 and 1992, Wb transmission decreased dramatically as evidenced by reduced prevalences of microfilariae (31% vs. 5%) and circulating Ag (CAg, 49% vs.,16%).,Age specific prevalence analysis showed a dramatic reduction in Wb123 Ab positivity from 54% (25/46) in 1975 to 8% (3/38) in 1992 in children 1-5 years (p<0.0001), reflecting the effects of single-dose treatment five years earlier.,By 1992, Wb123 Ab prevalence in children 6-10 years had fallen from 75% (42/56) in 1975 to 42% (33/79) consistent with a lower cumulative transmission potential.,In the whole population, Wb123 seropositivity decreased from 86% to 60% between 1975 and 1992.,In CAg+ subjects the levels of Wb123 Ab were indistinguishable between the 2 time points but differed in those who were CAg− (p<0.0001).,In paired sample analysis, individuals who were CAg+ in 1975 but became CAg− in 1992 had significantly lower Ab levels in 1992 (p<0.0001), with 9/40 (23%) becoming seronegative for Wb123.,The relationship between reduction in Wb123 Ab prevalence and the reduction of transmission, seen most clearly in young children, strongly advocates for the continuing assessment and rapid development of Wb123 as a surveillance tool to detect potential transmission of bancroftian filariasis in treated endemic areas.

In Mali, Plasmodium falciparum malaria is highly endemic and remains stable despite the implementation of various malaria control measures.,Understanding P. falciparum population structure variations across the country could provide new insights to guide malaria control programmes.,In this study, P. falciparum genetic diversity and population structure in regions of varying patterns of malaria transmission in Mali were analysed.,A total of 648 blood isolates adsorbed onto filter papers during population surveillance surveys (December 2012-March 2013, October 2013) in four distinct sites of Mali were screened for the presence of P. falciparum via quantitative PCR (qPCR).,Multiple loci variable number of tandem repeats analysis (MLVA) using eight microsatellite markers was then performed on positive qPCR samples.,Complete genotypes were then analysed for genetic diversity, genetic differentiation and linkage disequilibrium.,Of 156 qPCR-positive samples, complete genotyping of 112 samples was achieved.,The parasite populations displayed high genetic diversity (mean He = 0.77), which was consistent with a high level of malaria transmission in Mali.,Genetic differentiation was low (FST < 0.02), even between sites located approximately 900 km apart, thereby illustrating marked gene flux amongst parasite populations.,The lack of linkage disequilibrium further revealed an absence of local clonal expansion, which was corroborated by the genotype relationship results.,In contrast to the stable genetic diversity level observed throughout the country, mean multiplicity of infection increased from north to south (from 1.4 to 2.06) and paralleled malaria transmission levels observed locally.,In Mali, the high level of genetic diversity and the pronounced gene flux amongst P. falciparum populations may represent an obstacle to control malaria.,Indeed, results suggest that parasite populations are polymorphic enough to adapt to their host and to counteract interventions, such as anti-malarial vaccination.,Additionally, the panmictic parasite population structure imply that resistance traits may disseminate freely from one area to another, making control measures performed at a local level ineffective.,The online version of this article (doi:10.1186/s12936-016-1397-0) contains supplementary material, which is available to authorized users.

Swaziland has made great progress towards its goal of malaria elimination by 2015.,However, malaria importation from neighbouring high-endemic Mozambique through Swaziland’s eastern border remains a major factor that could prevent elimination from being achieved.,In order to reach elimination, Swaziland must rapidly identify and treat imported malaria cases before onward transmission occurs.,A nationwide formative assessment was conducted over eight weeks to determine if the imported cases of malaria identified by the Swaziland National Malaria Control Programme could be linked to broader social networks and to explore methods to access these networks.,Using a structured format, interviews were carried out with malaria surveillance agents (6), health providers (10), previously identified imported malaria cases (19) and people belonging to the networks identified through these interviews (25).,Most imported malaria cases were Mozambicans (63%, 12/19) making a living in Swaziland and sustaining their families in Mozambique.,The majority of imported cases (73%, 14/19) were labourers and self-employed contractors who travelled frequently to Mozambique to visit their families and conduct business.,Social networks of imported cases with similar travel patterns were identified through these interviews.,Nearly all imported cases (89%, 17/19) were willing to share contact information to enable network members to be interviewed.,Interviews of network members and key informants revealed common congregation points, such as the urban market places in Manzini and Malkerns, as well as certain bus stations, where people with similar travel patterns and malaria risk behaviours could be located and tested for malaria.,This study demonstrated that imported cases of malaria belonged to networks of people with similar travel patterns.,This study may provide novel methods for screening high-risk groups of travellers using both snowball sampling and time-location sampling of networks to identify and treat additional malaria cases.,Implementation of a proactive screening programme of importation networks may help Swaziland halt transmission and achieve malaria elimination by 2015.

A multidrug-resistant co-lineage of Plasmodium falciparum malaria, named KEL1/PLA1, spread across Cambodia in 2008-13, causing high rates of treatment failure with the frontline combination therapy dihydroartemisinin-piperaquine.,Here, we report on the evolution and spread of KEL1/PLA1 in subsequent years.,For this genomic epidemiology study, we analysed whole genome sequencing data from P falciparum clinical samples collected from patients with malaria between 2007 and 2018 from Cambodia, Laos, northeastern Thailand, and Vietnam, through the MalariaGEN P falciparum Community Project.,Previously unpublished samples were provided by two large-scale multisite projects: the Tracking Artemisinin Resistance Collaboration II (TRAC2) and the Genetic Reconnaissance in the Greater Mekong Subregion (GenRe-Mekong) project.,By investigating genome-wide relatedness between parasites, we inferred patterns of shared ancestry in the KEL1/PLA1 population.,We analysed 1673 whole genome sequences that passed quality filters, and determined KEL1/PLA1 status in 1615.,Before 2009, KEL1/PLA1 was only found in western Cambodia; by 2016-17 its prevalence had risen to higher than 50% in all of the surveyed countries except for Laos.,In northeastern Thailand and Vietnam, KEL1/PLA1 exceeded 80% of the most recent P falciparum parasites.,KEL1/PLA1 parasites maintained high genetic relatedness and low diversity, reflecting a recent common origin.,Several subgroups of highly related parasites have recently emerged within this co-lineage, with diverse geographical distributions.,The three largest of these subgroups (n=84, n=79, and n=47) mostly emerged since 2016 and were all present in Cambodia, Laos, and Vietnam.,These expanding subgroups carried new mutations in the crt gene, which arose on a specific genetic background comprising multiple genomic regions.,Four newly emerging crt mutations were rare in the early period and became more prevalent by 2016-17 (Thr93Ser, rising to 19·8%; His97Tyr to 11·2%; Phe145Ile to 5·5%; and Ile218Phe to 11·1%).,After emerging and circulating for several years within Cambodia, the P falciparum KEL1/PLA1 co-lineage diversified into multiple subgroups and acquired new genetic features, including novel crt mutations.,These subgroups have rapidly spread into neighbouring countries, suggesting enhanced fitness.,These findings highlight the urgent need for elimination of this increasingly drug-resistant parasite co-lineage, and the importance of genetic surveillance in accelerating malaria elimination efforts.,Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and UK Department for International Development.

In Plasmodium falciparum, resistance to chloroquine (CQ) is conferred by a K to T mutation at amino acid position 76 (K76T) in the P. falciparum CQ transporter (PfCRT).,To date, at least 15 pfcrt genotypes, which are represented by combinations of five amino acids at positions 72-76, have been described in field isolates from various endemic regions.,To identify novel mutant pfcrt genotypes and to reveal the genetic relatedness of pfcrt genotypes, a large-scale survey over a wide geographic area was performed.,Sequences for exon 2 in pfcrt, including known polymorphic sites at amino acid positions 72, 74, 75 and 76, were obtained from 256 P. falciparum isolates collected from eight endemic countries in Asia (Bangladesh, Cambodia, Lao P.D.R., the Philippines and Thailand), Melanesia (Papua New Guinea and Vanuatu) and Africa (Ghana).,A haplotype network was constructed based on six microsatellite markers located -29 kb to 24 kb from pfcrt in order to examine the genetic relatedness among mutant pfcrt genotypes.,In addition to wild type (CVMNK at positions 72-76), four mutant pfcrt were identified; CVIET, CVIDT, SVMNT and CVMNT (mutated amino acids underlined).,Haplotype network revealed that there were only three mutant pfcrt lineages, originating in Indochina, Philippines and Melanesia.,Importantly, the Indochina lineage contained two mutant pfcrt genotypes, CVIET (n = 95) and CVIDT (n = 14), indicating that CVIDT shares a common origin with CVIET.,Similarly, one major haplotype in the Melanesian lineage contained two pfcrt genotypes; SVMNT (n = 71) and CVMNT (n = 3).,In Africa, all mutant pfcrt genotypes were the CVIET of the Indochina lineage, probably resulting from the intercontinental migration of CQ resistance from Southeast Asia.,The number of CQ-mutant lineages observed in this study was identical to that found in previous studies.,This supports the hypothesis that the emergence of novel CQ resistance is rare.,However, in the mutant pfcrt genotypes, amino acid changes at positions 72, 74 and 75 appear to have recently been generated at least several times, producing distinct pfcrt mutant genotypes.,The occurrence of new mutations flanking K76T may yield stronger resistance to CQ and/or a higher fitness than the original pfcrt mutant.

Non-domiciliated intrusive triatomine vectors are responsible for a low but significant transmission of Trypanosoma cruzi to humans.,Their control is a challenge as insecticide spraying is of limited usefulness, and alternative strategies need to be developed for a sustainable control.,We performed a non-randomized controlled trial of an Ecohealth intervention based on window insect screens and community participation to reduce house infestation by Triatoma dimidiata in two rural villages in Yucatan, Mexico.,Efficacy of the intervention was measured over a three years follow-up period and entomological indicators showed that the proportion of triatomines found inside houses was significantly reduced in houses with insect screens, which effectively kept more bugs on the outside of houses.,Using a previously developed model linking entomological data to the prevalence of infection in human, we predicted that the intervention would lead to a 32% reduction in yearly incidence and in the prevalence of T. cruzi infection.,The cost for the coverage of all the windows of a house was of comparable magnitude to what families currently spend on various domestic insecticide, and most screens were still in good conditions after three years.,In conclusion, the Ecohealth approach proposed here is effective for the long-term and sustainable control of intrusive T. dimidiata vectors in the Yucatan peninsula, Mexico.,This strategy may also be easily adapted to other intrusive triatomine species as well as other regions/countries with comparable eco-epidemiological settings, and would be an excellent component of a larger integrated program for the control of a variety of other vector-borne diseases, bringing additional benefits to the communities.,Our results should encourage a further scaling-up of our implementation strategy in additional villages in the region.

To evaluate human risk for Chagas disease, we molecularly identified blood meal sources and prevalence of Trypanosoma cruzi infection among 49 Triatoma sanguisuga kissing bugs in Louisiana, USA.,Humans accounted for the second most frequent blood source.,Of the bugs that fed on humans, ≈40% were infected with T. cruzi, revealing transmission potential.

This paper summarises key advances and priorities since the 2011 presentation of the Malaria Eradication Research Agenda (malERA), with a focus on the combinations of intervention tools and strategies for elimination and their evaluation using modelling approaches.,With an increasing number of countries embarking on malaria elimination programmes, national and local decisions to select combinations of tools and deployment strategies directed at malaria elimination must address rapidly changing transmission patterns across diverse geographic areas.,However, not all of these approaches can be systematically evaluated in the field.,Thus, there is potential for modelling to investigate appropriate ‘packages’ of combined interventions that include various forms of vector control, case management, surveillance, and population-based approaches for different settings, particularly at lower transmission levels.,Modelling can help prioritise which intervention packages should be tested in field studies, suggest which intervention package should be used at a particular level or stratum of transmission intensity, estimate the risk of resurgence when scaling down specific interventions after local transmission is interrupted, and evaluate the risk and impact of parasite drug resistance and vector insecticide resistance.,However, modelling intervention package deployment against a heterogeneous transmission background is a challenge.,Further validation of malaria models should be pursued through an iterative process, whereby field data collected with the deployment of intervention packages is used to refine models and make them progressively more relevant for assessing and predicting elimination outcomes.,Richard Steketee and colleagues propose an updated research agenda for combination interventions and modelling in malaria elimination and eradication.

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.

In Brazil, 99% of the cases of malaria are concentrated in the Amazon region, with high level of transmission.,The objectives of the study were to use geographic information systems (GIS) analysis and logistic regression as a tool to identify and analyse the relative likelihood and its socio-environmental determinants of malaria infection in the Vale do Amanhecer rural settlement, Brazil.,A GIS database of georeferenced malaria cases, recorded in 2005, and multiple explanatory data layers was built, based on a multispectral Landsat 5 TM image, digital map of the settlement blocks and a SRTM digital elevation model.,Satellite imagery was used to map the spatial patterns of land use and cover (LUC) and to derive spectral indices of vegetation density (NDVI) and soil/vegetation humidity (VSHI).,An Euclidian distance operator was applied to measure proximity of domiciles to potential mosquito breeding habitats and gold mining areas.,The malaria risk model was generated by multiple logistic regression, in which environmental factors were considered as independent variables and the number of cases, binarized by a threshold value was the dependent variable.,Out of a total of 336 cases of malaria, 133 positive slides were from inhabitants at Road 08, which corresponds to 37.60% of the notifications.,The southern region of the settlement presented 276 cases and a greater number of domiciles in which more than ten cases/home were notified.,From these, 102 (30.36%) cases were caused by Plasmodium falciparum and 174 (51.79%) cases by Plasmodium vivax.,Malaria risk is the highest in the south of the settlement, associated with proximity to gold mining sites, intense land use, high levels of soil/vegetation humidity and low vegetation density.,Mid-resolution, remote sensing data and GIS-derived distance measures can be successfully combined with digital maps of the housing location of (non-) infected inhabitants to predict relative likelihood of disease infection through the analysis by logistic regression.,Obtained findings on the relation between malaria cases and environmental factors should be applied in the future for land use planning in rural settlements in the Southern Amazon to minimize risks of disease transmission.

Despite being free of charge, treatment adherence to 7-day primaquine for the radical cure of Plasmodium vivax was estimated at 62.2% among patients along the Iquitos-Nauta road in the Peruvian Amazon.,The principal reason for non-adherence was the perceived adverse effects related to local humoral illness conceptions that hold that malaria produces a hot state of body, which is further aggravated by the characteristically hot medical treatment.,Notably, patients were willing to adhere to the first 3 days of treatment during which symptoms are most apparent and include the characteristic chills.,Nevertheless, as symptoms abate, the perceived aggravating characteristics of the medication outweigh the perceived advantages of treatment adherence.,Improving community awareness about the role of primaquine to prevent further malaria transmission and fostering a realistic system of direct observed treatment intake, organized at community level, can be expected to improve adherence to the radical cure of P. vivax in this area.

Plasmodium knowlesi malaria causes severe disease in up to 10% of cases in Malaysian Borneo and has a mortality rate of 1 - 2%.,However, laboratory markers with the ability to identify patients at risk of developing complications have not yet been assessed as they have for other species of Plasmodium.,A case control study was undertaken in two hospitals in Sarikei and Sibu, Malaysian Borneo.,One hundred and ten patients with uncomplicated (n = 93) and severe (n = 17) P. knowlesi malaria were studied.,Standardized pigment-containing neutrophil (PCN) count, parasite density and platelet counts were determined and analysed by logistic regression and receiver operating characteristic (ROC) analysis.,The PCN count was strongly associated with risk of disease severity.,Patients with high parasite density (≥ 35,000/μl) or with thrombocytopaenia (≤ 45,000/μl) were also more likely to develop complications (odds ratio (OR) = 9.93 and OR = 5.27, respectively).,The PCN count yielded the highest area under the ROC curve (AUC) estimate among all markers of severity (AUC = 0.8561, 95% confidence interval: 0.7328, 0.9794).,However, the difference between all parameter AUC estimates was not statistically significant (Wald test, p = 0.73).,Counting PCN is labour-intensive and not superior in predicting severity over parasitaemia and platelet counts.,Parasite and platelet counts are simpler tests with an acceptable degree of precision.,Any adult patient diagnosed with P. knowlesi malaria and having a parasite count ≥35,000/μl or ≥1% or a platelet count ≤45,000/μl can be regarded at risk of developing complications and should be managed according to current WHO guidelines for the treatment of severe malaria.

Previously, Plasmodium knowlesi was not considered as a species of Plasmodium that could cause malaria in human beings, as it is parasite of long-tailed (Macaca fascicularis) and pig-tailed (Macaca nemestrina) macaques found in Southeast Asia.,A case of infection by P. knowlesi is described in a Spanish traveller, who came back to Spain with daily fever after his last overseas travel, which was a six-month holiday in forested areas of Southeast Asia between 2008 and 2009.,His P. knowlesi infection was detected by multiplex Real time quantitative PCR and confirmed by sequencing the amplified fragment.,Using nested multiplex malaria PCR (reference method in Spain) and a rapid diagnostic test, the P. knowlesi infection was negative.,This patient was discharged and asymptomatic when the positive result to P. knowlesi was reported.,Prior to this case, there have been two more reports of European travellers with malaria caused by P. knowlesi, a Finnish man who travelled to Peninsular Malaysia during four weeks in March 2007, and a Swedish man who did a short visit to Malaysian Borneo in October 2006.,Taken together with this report of P. knowlesi infection in a Spanish traveller returning from Southeast Asia, this is the third case of P. knowlesi infection in Europe, indicating that this simian parasite can infect visitors to endemic areas in Southeast Asia.,This last European case is quite surprising, given that it is an untreated-symptomatic P. knowlesi in human, in contrast to what is currently known about P. knowlesi infection.,Most previous reports of human P. knowlesi malaria infections were in adults, often with symptoms and relatively high parasite densities, up to the recent report in Ninh Thuan province, located in the southern part of central Vietnam, inhabited mainly by the Ra-glai ethnic minority, in which all P. knowlesi infections were asymptomatic, co-infected with P. malariae, with low parasite densities and two of the three identified cases were very young children under five years old.

We characterized the immune responses elicited by a DNA-prime/MVA-boost vaccine (TcVac3) constituted of antigenic candidates (TcG2 and TcG4), shown to be recognized by B and T cell responses in Trypanosoma cruzi (Tc) infected multiple hosts.,C57BL/6 mice immunized with TcVac3 elicited a strong antigen-specific, high-avidity, trypanolytic antibody response (IgG2b>IgG1); and a robust antigen- and Tc-specific CD8+T cell response with type-1 cytokine (IFN-γ+TNF-α>IL-4+IL-10) and cytolytic effector (CD8+CD107a+IFN-γ+Perforin+) phenotype.,The vaccine-induced effector T cells significantly expanded upon challenge infection and provided >92% control of T. cruzi.,Co-delivery of IL-12 and GMCSF cytokine adjuvants didn’t enhance the TcVac3-induced resistance to T. cruzi.,In chronic phase, vaccinated/infected mice exhibited a significant decline (up to 70%) in IFN-γ+CD8+T cells, a predominance of immunoregulatory IL-10+/CD4+T and IL10+/CD8+T cells, and presented undetectable tissue parasitism, inflammatory infiltrate, and fibrosis in vaccinated/infected mice.,In comparison, control mice responded to challenge infection by a low antibody response, mixed cytokine profile, and consistent activation of pro-inflammatory CD8+T cells associated with parasite persistence and pathologic damage in the heart.,We conclude that TcVac3 elicited type-1 effector T cell immunity that effectively controlled T. cruzi infection, and subsequently, predominance of anti-inflammatory responses prevented chronic inflammation and myocarditis in chagasic mice.

Immunization of mice with the Trypanosoma cruzi trans-sialidase (TS) gene using plasmid DNA, adenoviral vector, and CpG-adjuvanted protein delivery has proven highly immunogenic and provides protection against acute lethal challenge.,However, long-term protection induced by TS DNA vaccines has not been reported.,The goal of the present work was to test whether the co-administration of a plasmid encoding IL-15 (pIL-15) could improve the duration of protection achieved through genetic vaccination with plasmid encoding TS (pTS) alone.,We immunized BALB/c mice with pTS in the presence or absence of pIL-15 and studied immune responses [with TS-specific IFN-γ ELISPOT, serum IgG ELISAs, intracellular cytokine staining (IFN-γ, TNF-α, and IL-2), tetramer staining, and CFSE dilution assays] and protection against lethal systemic challenge at 1 to 6 months post vaccination.,Mice receiving pTS alone developed robust TS-specific IFN-γ responses and survived a lethal challenge given within the first 3 months following immunization.,The addition of pIL-15 to pTS vaccination did not significantly alter T cell responses or protection during this early post-vaccination period.,However, mice vaccinated with both pTS and pIL-15 challenged 6 months post-vaccination were significantly more protected against lethal T. cruzi challenges than mice vaccinated with pTS alone (P<0.05).,Improved protection correlated with significantly higher numbers of TS-specific IFN-γ producing total and CD8+ T cells detected>6 months post immunization.,Also, these TS-specific T cells were better able to expand after in vitro re-stimulation.,Addition of pIL-15 during genetic vaccination greatly improved long-term T cell survival, memory T cell expansion, and long-term protection against the important human parasite, T. cruzi.

In the progress towards malaria elimination, the accurate diagnosis of low-density asymptomatic infections is critical.,Low-density asymptomatic submicroscopic malaria infections may act as silent reservoirs that maintain low-level residual malaria transmission in the community.,Light microscopy, the gold standard in malaria diagnosis lacks the sensitivity to detect low-level parasitaemia.,In this study, the presence and prevalence of submicroscopic Plasmodium carriage were investigated to estimate the parasites reservoir among asymptomatic individuals living in low transmission areas in Dielmo and Ndiop, Senegal during the dry season.,A total of 2,037 blood samples were collected during cross-sectional surveys prior the malaria transmission season in July 2013 (N = 612), June 2014 (N = 723) and June 2015 (N = 702) from asymptomatic individuals living in Dielmo and Ndiop, Senegal.,Samples were used to determine the prevalence of submicroscopic Plasmodium carriage by real time PCR (qPCR) in comparison to microscopy considered as gold standard.,The prevalence of submicroscopic Plasmodium carriage was 3.75% (23/612), 12.44% (90/723) and 6.41% (45/702) in 2013, 2014 and 2015, respectively.,No Plasmodium carriage was detected by microscopy in 2013 while microscopy-based prevalence of Plasmodium carriage accounted for only 0.27% (2/723) and 0.14% (1/702) in 2014 and 2015, respectively.,Plasmodium falciparum accounted for the majority of submicroscopic infections and represented 86.95% (20/23), 81.11% (73/90) and 95.55 (43/45) of infections in 2013, 2014 and 2015 respectively.,Low-density submicroscopic asymptomatic Plasmodium carriage is common in the study areas during the dry season indicating that traditional measures are insufficient to assess the scale of parasite reservoir when transmission reaches very low level.,Control and elimination strategies may wish to consider using molecular methods to identify parasites carriers to guide Mass screening and Treatment strategies.

Previous analyses have suggested that immunity to non-cerebral severe malaria due to Plasmodium falciparum is acquired after only a few infections, whereas longitudinal studies show that some children experience multiple episodes of severe disease, suggesting that immunity may not be acquired so quickly.,We fitted a mathematical model for the acquisition and loss of immunity to severe disease to the age distribution of severe malaria cases stratified by symptoms from a range of transmission settings in Tanzania, combined with data from several African countries on the age distribution and overall incidence of severe malaria.,We found that immunity to severe disease was acquired more gradually with exposure than previously thought.,The model also suggests that physiological changes, rather than exposure, may alter the symptoms of disease with increasing age, suggesting that a later age at infection would be associated with a higher proportion of cases presenting with cerebral malaria regardless of exposure.,This has consequences for the expected pattern of severe disease as transmission changes.,Careful monitoring of the decline in immunity associated with reduced transmission will therefore be needed to ensure rebound epidemics of severe and fatal malaria are avoided.

Significant progress has been made in the prevention, control, and elimination of human parasitic diseases in China in the past 60 years.,However, parasitic diseases of poverty remain major causes of morbidity and mortality, and inflict enormous economic costs on societies.,In this article, we review the prevalence rates, geographical distributions, epidemic characteristics, risk factors, and clinical manifestations of parasitic diseases of poverty listed in the first issue of the journal Infectious Diseases of Poverty on 25 October 2012.,We also address the challenges facing control of parasitic diseases of poverty and provide suggestions for better control.,The online version of this article (doi:10.1186/s40249-016-0159-0) contains supplementary material, which is available to authorized users.

More than 80% of schistosomiasis patients in China live in the lake and marshland regions.,The purpose of our study is to assess the effect of a comprehensive strategy to control transmission of Schistosoma japonicum in marshland regions.,In a cluster randomized controlled trial, we implemented an integrated control strategy in twelve villages from 2009 through 2011 in Gong'an County, Hubei Province.,The routine interventions included praziquantel chemotherapy and controlling snails, and were implemented in all villages.,New interventions, mainly consisting of building fences to limit the grazing area for bovines, building safe pastures for grazing, improving the residents' health conditions and facilities, were only implemented in six intervention villages.,Results showed that the rate of S. japonicum infection in humans, bovines, snails, cow dung and mice in the intervention group decreased from 3.41% in 2008 to 0.81% in 2011, 3.3% to none, 11 of 6,219 to none, 3.9% to none and 31.7% to 1.7%, respectively (P<0.001 for all comparisons).,In contrast, there were no statistically significant reductions of S. japonicum infection in humans, bovines and snails from 2008 to 2011 in the control group (P>0.05 for all comparisons).,Moreover, a generalized linear model showed that there was a higher infection risk in humans in the control group than in the intervention group (OR = 1.250, P = 0.001) and an overall significant downward trend in infection risk during the study period.,The integrated control strategy, designed to reduce the role of bovines and humans as sources of S. japonicum infection, was highly effective in controlling the transmission of S. japonicum in marshland regions in China.,Chinese Clinical Trial Registry ChiCTR-PRC-12002405.

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.

Clonally variant protein expression in the malaria parasite Plasmodium falciparum generates phenotypic variability and allows isogenic populations to adapt to environmental changes encountered during blood stage infection.,The underlying regulatory mechanisms are best studied for the major virulence factor P. falciparum erythrocyte membrane protein 1 (PfEMP1).,PfEMP1 is encoded by the multicopy var gene family and only a single variant is expressed in individual parasites, a concept known as mutual exclusion or singular gene choice. var gene activation occurs in situ and is achieved through the escape of one locus from epigenetic silencing.,Singular gene choice is controlled at the level of transcription initiation and var 5′ upstream (ups) sequences harbour regulatory information essential for mutually exclusive transcription as well as for the trans-generational inheritance of the var activity profile.,An additional level of control has recently been identified for the var2csa gene, where an mRNA element in the 5′ untranslated region (5′ UTR) is involved in the reversible inhibition of translation of var2csa transcripts.,Here, we extend the knowledge on post-transcriptional var gene regulation to the common upsC type.,We identified a 5′ UTR sequence that inhibits translation of upsC-derived mRNAs.,Importantly, this 5′ UTR element efficiently inhibits translation even in the context of a heterologous upstream region.,Further, we found var 5′ UTRs to be significantly enriched in uAUGs which are known to impair the efficiency of protein translation in other eukaryotes.,Our findings suggest that regulation at the post-transcriptional level is a common feature in the control of PfEMP1 expression in P. falciparum.

The malaria parasite species, Plasmodium vivax infects not only humans, but also African apes.,Human specific P. vivax has evolved from a single ancestor that originated from a parasite of African apes.,Although previous studies have proposed phylogenetic trees positioning P. vivax (the common ancestor of human and African ape P. vivax) within the assemblages of Asian primate parasites, its position has not yet been robustly confirmed.,We determined nearly complete apicoplast genome sequences from seven Asian primate parasites, Plasmodium cynomolgi (strains Ceylonensis and Berok), P. knowlesi P. fragile, P. fieldi, P. simiovale, P. hylobati, P. inui, and an African primate parasite, P. gonderi, that infects African guenon.,Phylogenetic relationships of the Plasmodium species were analyzed using newly and previously determined apicoplast genome sequences.,Multigene maximum likelihood analysis of 30 protein coding genes did not position P. vivax within the Asian primate parasite clade but positioned it basal to the clade, after the branching of an African guenon parasite, P. gonderi.,The result does not contradict with the emerging notion that P. vivax phylogenetically originated from Africa.,The result is also supported by phylogenetic analyses performed using massive nuclear genome data of seven primate Plasmodium species.

Land use changes disrupt ecosystems, altering the transmission of vector-borne diseases.,These changes have been associated with increasing incidence of zoonotic malaria caused by Plasmodium knowlesi; however, the population-level distributions of infection and exposure remain unknown.,We aimed to measure prevalence of serological exposure to P knowlesi and assess associated risk factors.,We did an environmentally stratified, population-based, cross-sectional survey across households in the Kudat, Kota Marudu, Pitas, and Ranau districts in northern Sabah, Malaysia, encompassing a range of ecologies.,Using blood samples, the transmission intensity of P knowlesi and other malaria species was measured by specific antibody prevalence and infection detected using molecular methods.,Proportions and configurations of land types were extracted from maps derived from satellite images; a data-mining approach was used to select variables.,A Bayesian hierarchical model for P knowlesi seropositivity was developed, incorporating questionnaire data about individual and household-level risk factors with selected landscape factors.,Between Sept 17, 2015, and Dec 12, 2015, 10 100 individuals with a median age of 25 years (range 3 months to 105 years) were sampled from 2849 households in 180 villages.,5·1% (95% CI 4·8-5·4) were seropositive for P knowlesi, and marked historical decreases were observed in the transmission of Plasmodium falciparum and Plasmodium vivax.,Nine Plasmodium spp infections were detected.,Age, male sex, contact with macaques, forest use, and raised house construction were positively associated with P knowlesi exposure, whereas residing at higher geographical elevations and use of insecticide were protective.,Agricultural and forest variables, such as proportions and fragmentation of land cover types, predicted exposure at different spatial scales from households.,Although few infections were detected, P knowlesi exposure was observed in all demographic groups and was associated with occupational factors.,Results suggest that agricultural expansion and forest fragmentation affect P knowlesi exposure, supporting linkages between land use change and P knowlesi transmission.,UK Medical Research Council, Natural Environment Research Council, Economic and Social Research Council, and Biotechnology and Biosciences Research Council.

Protective antibodies in Plasmodium falciparum malaria are only acquired after years of repeated infections.,Chronic malaria exposure is associated with a large increase in atypical memory B cells (MBCs) that resemble B cells expanded in a variety of persistent viral infections.,Understanding the function of atypical MBCs and their relationship to classical MBCs will be critical to developing effective vaccines for malaria and other chronic infections.,We show that VH gene repertoires and somatic hypermutation rates of atypical and classical MBCs are indistinguishable indicating a common developmental history.,Atypical MBCs express an array of inhibitory receptors and B cell receptor (BCR) signaling is stunted in atypical MBCs resulting in impaired B cell responses including proliferation, cytokine production and antibody secretion.,Thus, in response to chronic malaria exposure, atypical MBCs appear to differentiate from classical MBCs becoming refractory to BCR-mediated activation and potentially interfering with the acquisition of malaria immunity.,DOI:http://dx.doi.org/10.7554/eLife.07218.001,The human immune system works to protect individuals from harmful microbes, such as the parasites that cause malaria.,One line of defense is to produce a large array of proteins called antibodies that specifically bind to microbes to mark them for destruction by the immune system.,The immune system also produces long-lived memory B cells that are able to mount a quicker and more effective antibody response if the microbe enters the body again.,This means that most people only become ill with a particular disease the first time they encounter the microbe that causes it.,However, malaria is unusual in that it can take many years of exposure to the parasite that causes it before an individual produces enough antibodies and memory B cells to be protected from the disease.,There is also no vaccine that provides effective and long-lasting protection against malaria.,Vaccinations rely on stimulating the body's natural defenses, and so understanding more about antibodies and memory B cells in relation to malaria may aid future efforts to develop a vaccine.,Researchers have discovered that many of the memory B cells that accumulate in people who have been exposed to the malaria parasite over long-periods of time are different from the normal memory B cells.,But it was not clear what role these ‘atypical’ cells play in immunity to malaria.,To address this question, Portugal et al. studied the genetics and activity of B cells collected from children and adults living in Mali who-by living in a region where malaria is common-had been repeatedly exposed to the parasite.,The experiments indicate that atypical and normal memory B cells both develop from the same precursor cells.,However, the genes that are active in each cell type are different, resulting in the atypical cells being less able to respond to the parasite than the normal memory B cells.,Portugal et al.'s findings suggest that the atypical cells develop from normal memory B cells during long-term exposure to malaria, which may delay the development of immunity to this disease.,Future challenges include understanding what drives the formation of the atypical memory B cells in malaria, and finding out why they are less active than the normal cells.,This could aid the development of vaccines and/or therapies that restore their activity in patients.,DOI:http://dx.doi.org/10.7554/eLife.07218.002

The balance between pro-inflammatory and regulatory immune responses in determining optimal T cell activation is vital for the successful resolution of microbial infections.,This balance is maintained in part by the negative regulators of T cell activation, CTLA-4 and PD-1/PD-L, which dampen effector responses during chronic infections.,However, their role in acute infections, such as malaria, remains less clear.,In this study, we determined the contribution of CTLA-4 and PD-1/PD-L to the regulation of T cell responses during Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM) in susceptible (C57BL/6) and resistant (BALB/c) mice.,We found that the expression of CTLA-4 and PD-1 on T cells correlates with the extent of pro-inflammatory responses induced during PbA infection, being higher in C57BL/6 than in BALB/c mice.,Thus, ECM develops despite high levels of expression of these inhibitory receptors.,However, antibody-mediated blockade of either the CTLA-4 or PD-1/PD-L1, but not the PD-1/PD-L2, pathways during PbA-infection in ECM-resistant BALB/c mice resulted in higher levels of T cell activation, enhanced IFN-γ production, increased intravascular arrest of both parasitised erythrocytes and CD8+ T cells to the brain, and augmented incidence of ECM.,Thus, in ECM-resistant BALB/c mice, CTLA-4 and PD-1/PD-L1 represent essential, independent and non-redundant pathways for maintaining T cell homeostasis during a virulent malaria infection.,Moreover, neutralisation of IFN-γ or depletion of CD8+ T cells during PbA infection was shown to reverse the pathologic effects of regulatory pathway blockade, highlighting that the aetiology of ECM in the BALB/c mice is similar to that in C57BL/6 mice.,In summary, our results underscore the differential and complex regulation that governs immune responses to malaria parasites.

There are few drugs with proven efficacy in cutaneous leishmaniasis (CL), and pentavalent antimonial derivatives are still the main first-line therapeutic agents worldwide, despite their recognized high toxicities.,Randomized controlled clinical trials assessing the efficacy and safety of new therapeutic modalities are of high priority, and the definition of the design of such trials raises debate about the use of placebo as a comparator.,To support the use of placebo as a comparator, two main points need to be addressed: 1- the cure rate without any therapeutic intervention and 2- the damage caused by CL and its impact on patients.,The aim of this study was to systematically assess the spontaneous cure rate for American CL and to broaden the discussion about placebo use in CL trials.,The PRISMA guidelines for systematic reviews and the Cochrane manual were followed.,The sources used were the PubMed and LILACS databases.,Studies were included if they reported cure rates using placebo or no treatment in American CL.,Thirteen studies of a total of 352 patients were ultimately included in this review.,The summarized global cure rates for all Leishmania species according to the intention-to-treat analyses performed at approximately three (“initial cure”) and nine (“definitive cure”) months after “no treatment” or placebo use were 26% (CI95%: 16 to 40%) and 26% (CI95%:16 to 38%), respectively.,Notably, a significantly lower cure rate was observed for L. braziliensis infection (6.4%, CI95%:0.2 to 20%) than for L. mexicana infection (44%, CI95%:19 to 72%), p = 0.002.,Of note, relapse occurred in 20% of patients with initial healing (CI95%:9.2 to 38.9%).,These results clearly demonstrate a low spontaneous cure rate following no-treatment or placebo use, confirming that this strategy for the control group in CL studies expose patients to greater morbidity, especially for CL caused by L. braziliensis.,Therefore, from this point, the crucial questionto consider regarding placebo use isthe seriousness of the suffering caused by this disease.

Visceral leishmaniasis (VL) or kala-azar is a chronic protozoan infection in humans associated with significant global morbidity and mortality.,The causative agent is a haemoflagellate protozoan Leishmania donovani, an obligate intracellular parasite that resides and multiplies within macrophages of the reticulo-endothelial system.,Most of the existing anti-leishmanial drugs have serious side effects that limit their clinical application.,As an alternate strategy, vaccination is also under experimental and clinical trials.,The in vitro evaluation designed to facilitate rapid testing of a large number of drugs has been focussed on the promastigotes milt little attention on the clinically relevant parasite stage, amastigotes.,Screening designed to closely reflect the situation in vivo is currently time consuming, laborious, and expensive, since it requires intracellular amastigotes and animal model.,The ability to select transgenic Leishmania expressing reporter proteins, such as the green fluorescent proteins (GFP) or the luciferase opened up new possibilities for the development of drug screening models.,Many experimental animal models like rodents, dogs and monkeys have been developed, each with specific features, but none accurately reproduces what happens in humans.,Available in vitro and in vivo methodologies for antileishmanial drug screening and their respective advantages and disadvantages are reviewed.

Visceral leishmaniasis (VL) is a predominantly rural disease, common in the low lands of eastern Nepal.,Since 1997 VL cases have also been reported among residents of the city of Dharan.,Our main research objective was to find out whether there had been local transmission of VL inside the city.,We conducted an outbreak investigation including a case-control study; cases were all urban residents treated for VL between 2000 and 2008 at BP Koirala Institute of Health Sciences, a university hospital in the city.,For each case, we selected four random controls, with no history of previous VL; frequency-matched for age.,Cases and controls were subjected to a structured interview on the main exposures of interest and potential confounders; a binominal multilevel model was used to analyze the data.,We also collected entomological data from all neighborhoods of the city.,We enrolled 115 VL patients and 448 controls.,Cases were strongly clustered, 70% residing in 3 out of 19 neighborhoods.,We found a strong association with socio-economic status, the poorest being most at risk.,Housing was a risk factor independent from socio-economic status, most at risk were those living in thatched houses without windows.,‘Sleeping upstairs’ and ‘sleeping on a bed’ were strongly protective, OR of 0.08 and 0.25 respectively; proximity to a case was a strong risk factor (OR 3.79).,Sand flies were captured in all neighborhoods; in collections from several neighborhoods presence of L. donovani could be demonstrated by PCR.,The evidence found in this study is consistent with transmission of anthroponotic VL within the city.,The vector P. argentipes and the parasite L. donovani have both been identified inside the town.,These findings are highly relevant for policy makers; in VL endemic areas appropriate surveillance and disease control measures must be adopted not only in rural areas but in urban areas as well.

Proximity of Leishmania donovani-positive goats is a risk factor for human infection.,On the Indian subcontinent, visceral leishmaniasis (VL) is considered an anthroponosis.,To determine possible reasons for its persistence during interepidemic periods, we mapped Leishmania infections among healthy persons and animals in an area of active VL transmission in Nepal.,During 4 months (September 2007-February 2008), blood was collected from persons, goats, cows, and buffaloes in 1 village.,Leishmania infections were determined by using PCR.,We found infections among persons (6.1%), cows (5%), buffaloes (4%), and goats (16%).,Data were georeferenced and entered into a geographic information system.,The bivariate K-function results indicated spatial clustering of Leishmania spp.-positive persons and domestic animals.,Classification tree analysis determined that among several possible risk factors for Leishmania infection among persons, proximity of Leishmania spp.-positive goats ranked first.,Although our data do not necessarily mean that goats constitute a reservoir host of L. donovani, these observations indicate the need for further investigation of goats’ possible role in VL transmission.

Loop-mediated isothermal DNA amplification (LAMP) methodology offers an opportunity for point-of-care (POC) molecular detection of asymptomatic malaria infections.,However, there is still little evidence on the feasibility of implementing this technique for population screenings in isolated field settings.,Overall, we recruited 1167 individuals from terrestrial (‘road’) and hydric (‘riverine’) communities of the Peruvian Amazon for a cross-sectional survey to detect asymptomatic malaria infections.,The technical performance of LAMP was evaluated in a subgroup of 503 samples, using real-time Polymerase Chain Reaction (qPCR) as reference standard.,The operational feasibility of introducing LAMP testing in the mobile screening campaigns was assessed based on field-suitability parameters, along with a pilot POC-LAMP assay in a riverine community without laboratory infrastructure.,LAMP had a sensitivity of 91.8% (87.7-94.9) and specificity of 91.9% (87.8-95.0), and the overall accuracy was significantly better among samples collected during road screenings than riverine communities (p≤0.004).,LAMP-based diagnostic strategy was successfully implemented within the field-team logistics and the POC-LAMP pilot in the riverine community allowed for a reduction in the turnaround time for case management, from 12-24 hours to less than 5 hours.,Specimens with haemolytic appearance were regularly observed in riverine screenings and could help explaining the hindered performance/interpretation of the LAMP reaction in these communities.,LAMP-based molecular malaria diagnosis can be deployed outside of reference laboratories, providing similar performance as qPCR.,However, scale-up in remote field settings such as riverine communities needs to consider a number of logistical challenges (e.g. environmental conditions, labour-intensiveness in large population screenings) that can influence its optimal implementation.

Detection of histidine-rich protein 2 (HRP2) from the malaria parasite Plasmodium falciparum provides evidence for active or recent infection, and is utilized for both diagnostic and surveillance purposes, but current laboratory immunoassays for HRP2 are hindered by low sensitivities and high costs.,Here we present a new HRP2 immunoassay based on antigen capture through a bead-based system capable of detecting HRP2 at sub-picogram levels.,The assay is highly specific and cost-effective, allowing fast processing and screening of large numbers of samples.,We utilized the assay to assess results of HRP2-based rapid diagnostic tests (RDTs) in different P. falciparum transmission settings, generating estimates for true performance in the field.,Through this method of external validation, HRP2 RDTs were found to perform well in the high-endemic areas of Mozambique and Angola with 86.4% and 73.9% of persons with HRP2 in their blood testing positive by RDTs, respectively, and false-positive rates of 4.3% and 0.5%.,However, in the low-endemic setting of Haiti, only 14.5% of persons found to be HRP2 positive by the bead assay were RDT positive.,Additionally, 62.5% of Haitians showing a positive RDT test had no detectable HRP2 by the bead assay, likely indicating that these were false positive tests.,In addition to RDT validation, HRP2 biomass was assessed for the populations in these different settings, and may provide an additional metric by which to estimate P. falciparum transmission intensity and measure the impact of interventions.

Malaria-associated acute respiratory distress syndrome (ARDS) is an inflammatory disease causing alveolar-pulmonary barrier lesion and increased vascular permeability characterized by severe hypoxemia.,Computed tomography (CT), among other imaging techniques, allows the morphological and quantitative identification of lung lesions during ARDS.,This study aims to identify the onset of malaria-associated ARDS development in an experimental model by imaging diagnosis.,Our results demonstrated that ARDS-developing mice presented decreased gaseous exchange and pulmonary insufficiency, as shown by the SPECT/CT technique.,The pulmonary aeration disturbance in ARDS-developing mice on the 5th day post infection was characterized by aerated tissues decrease and nonaerated tissue accumulation, demonstrating increased vascular permeability and pleural effusion.,The SPECT/CT technique allowed the early diagnosis in the experimental model, as well as the identification of the pulmonary aeration.,Notwithstanding, despite the fact that this study contributes to better understand lung lesions during malaria-associated ARDS, further imaging studies are needed.

Malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014.,When manifesting in the lungs, severe malaria causes acute lung injury/acute respiratory distress syndrome (ALI/ARDS).,We have previously shown that a proportion of DBA/2 mice infected with Plasmodium berghei ANKA (PbA) develop ALI/ARDS and that these mice recapitulate various aspects of the human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion and hypoxemia.,Herein, we investigated the role of neutrophils in the pathogenesis of malaria-associated ALI/ARDS.,Mice developing ALI/ARDS showed greater neutrophil accumulation in the lungs compared with mice that did not develop pulmonary complications.,In addition, mice with ALI/ARDS produced more neutrophil-attracting chemokines, myeloperoxidase and reactive oxygen species.,We also observed that the parasites Plasmodium falciparum and PbA induced the formation of neutrophil extracellular traps (NETs) ex vivo, which were associated with inflammation and tissue injury.,The depletion of neutrophils, treatment with AMD3100 (a CXCR4 antagonist), Pulmozyme (human recombinant DNase) or Sivelestat (inhibitor of neutrophil elastase) decreased the development of malaria-associated ALI/ARDS and significantly increased mouse survival.,This study implicates neutrophils and NETs in the genesis of experimentally induced malaria-associated ALI/ARDS and proposes a new therapeutic approach to improve the prognosis of severe malaria.

Trichomonas vaginalis (TV) infection is common, curable, and associated with significant reproductive morbidity and risk for HIV infection.,This analysis updates estimates of the prevalence of asymptomatic TV infection, and its associated risk factors, in the non-institutionalized U.S. population.,We analyzed data from 4057 individuals who participated in the National Health and Nutrition Examination Survey (NHANES) 2013-2014 data collection cycle.,Participant interviews ascertained demographic characteristics, self-reported tobacco use, and sexual history.,Self-collected urine specimens from participants aged 18 to 59 years were tested for TV infection using the Gen-Probe Aptima TV assay.,Cotinine was assayed from serum to provide a biomarker of recent tobacco exposure.,Weighted percentages are provided to account for unequal selection probabilities among participants and adjustments for non-response.,Our sample included 1942 men (49.2%, 95% Confidence Interval [CI] 48.0-50.5) and 2115 women (50.8%, 95%CI 49.5-52.0).,The infection prevalence among men was 0.5% (n = 16; 95%CI 0.2-1.0) and 1.8% (n = 55; 95%CI 1.1-3.1) in women.,After controlling for participant characteristics associated with TV infection, females had a 5.2-fold increased odds of being infected compared to men (adjusted odds ratio (aOR) 5.2, 95% CI 2.4-11.4).,Non-Hispanic blacks were more likely to be infected compared to non-Hispanic whites (aOR 11.2, 95% CI 4.6-27.2).,Individuals below the federal poverty level were more likely to be infected compared to those earning >3 times the federal poverty level (aOR 6.7, 95% CI 1.7-26.6), and active smokers were more likely to be infected compared to participants with no nicotine exposure (aOR 8.7, 95% CI 4.1-18.2).,Trichomonas vaginalis infection continues to be relatively common, especially in women, smokers, non-Hispanic blacks, and in groups of lower socioeconomic status.,Identifying the demographic characteristics of populations in the United States disproportionately affected by TV could impact screening and treatment of this infection in clinical practice.,Further research on whether screening and treating for asymptomatic TV infection in high-risk populations improves risk for reproductive morbidity and HIV infection is warranted.

We assessed knowledge, attitudes, and practices concerning trichomoniasis of American College of Obstetricians and Gynecologists members, finding discrepancies between practice and recommendations in screening/treatment of human immunodeficiency virus-positive patients and retesting/retreatment.,Trichomoniasis is the most prevalent nonviral sexually transmitted infection (STI) in the United States.,It can present with vaginitis in women and urethritis in men, but is most often asymptomatic or occurs with minimal symptoms.,It is associated with other STIs, adverse pregnancy outcomes and pelvic inflammatory disease.,For these reasons, health care provider awareness of trichomoniasis is of public health importance.,To assess practitioner knowledge, attitudes, and practices concerning trichomoniasis management, the American College of Obstetricians and Gynecologists conducted an online survey in 2016 of its members, and we analyzed results from 230 respondents.,We note discrepancies between practice and recommendations among surveyed providers: a minority of respondents routinely screen human immunodeficiency virus (HIV)-positive patients for trichomoniasis (10.7%, “most of the time”; 95% confidence interval [CI], 6.7-15.8; 33.0%, “always”; 95% CI, 26.5%-40.0%), treat trichomoniasis in HIV-positive patients with the recommended dose of metronidazole 500 mg twice a day for 7 days (25.8%; 95% CI, 20.0%-32.3%), or retest patients diagnosed with trichomoniasis 3 months after treatment (9.6%; 95% CI, 6.1%-14.3%).,Only 29.0% (95% CI, 23.0%-35.5%) retreat with metronidazole 500 mg twice a day for 7 days in patients who have failed prior treatment.,Screening for and treatment of trichomoniasis in HIV-positive patients, and retesting and retreatment for trichomoniasis in the general population appear to be suboptimal.,Continuing education for providers is needed for this common but “neglected” STI.

Chagas disease or American trypanosomiasis is, together with geohelminths, the neglected disease that causes more loss of years of healthy life due to disability in Latin America.,Chagas disease, as determined by the factors and determinants, shows that different contexts require different actions, preventing new cases or reducing the burden of disease.,Control strategies must combine two general courses of action including prevention of transmission to prevent the occurrence of new cases (these measures are cost effective), as well as opportune diagnosis and treatment of infected individuals in order to prevent the clinical evolution of the disease and to allow them to recuperate their health.,All actions should be implemented as fully as possible and with an integrated way, to maximise the impact.,Chagas disease cannot be eradicated due because of the demonstrated existence of infected wild triatomines in permanent contact with domestic cycles and it contributes to the occurrence of at least few new cases.,However, it is possible to interrupt the transmission of Trypanosoma cruzi in a large territory and to eliminate Chagas disease as a public health problem with a dramatic reduction of burden of the disease.

Although it has been known for nearly a century that strains of Trypanosoma cruzi, the etiological agent for Chagas' disease, are enzootic in the southern U.S., much remains unknown about the dynamics of its transmission in the sylvatic cycles that maintain it, including the relative importance of different transmission routes.,Mathematical models can fill in gaps where field and lab data are difficult to collect, but they need as inputs the values of certain key demographic and epidemiological quantities which parametrize the models.,In particular, they determine whether saturation occurs in the contact processes that communicate the infection between the two populations.,Concentrating on raccoons, opossums, and woodrats as hosts in Texas and the southeastern U.S., and the vectors Triatoma sanguisuga and Triatoma gerstaeckeri, we use an exhaustive literature review to derive estimates for fundamental parameters, and use simple mathematical models to illustrate a method for estimating infection rates indirectly based on prevalence data.,Results are used to draw conclusions about saturation and which population density drives each of the two contact-based infection processes (stercorarian/bloodborne and oral).,Analysis suggests that the vector feeding process associated with stercorarian transmission to hosts and bloodborne transmission to vectors is limited by the population density of vectors when dealing with woodrats, but by that of hosts when dealing with raccoons and opossums, while the predation of hosts on vectors which drives oral transmission to hosts is limited by the population density of hosts.,Confidence in these conclusions is limited by a severe paucity of data underlying associated parameter estimates, but the approaches developed here can also be applied to the study of other vector-borne infections.

The life-threatening diseases alveolar and cystic echinococcoses are caused by larvae of the tapeworms Echinococcus multilocularis and E. granulosus, respectively.,In both cases, intermediate hosts, such as humans, are infected by oral uptake of oncosphere larvae, followed by asexual multiplication and almost unrestricted growth of the metacestode within host organs.,Besides surgery, echinococcosis treatment relies on benzimidazole-based chemotherapy, directed against parasite beta-tubulin.,However, since beta-tubulins are highly similar between cestodes and humans, benzimidazoles can only be applied at parasitostatic doses and are associated with adverse side effects.,Mostly aiming at identifying alternative drug targets, the nuclear genome sequences of E. multilocularis and E. granulosus have recently been characterized, revealing a large number of druggable targets that are expressed by the metacestode.,Furthermore, recent cell biological investigations have demonstrated that E. multilocularis employs pluripotent stem cells, called germinative cells, which are the only parasite cells capable of proliferation and which give rise to all differentiated cells.,Hence, the germinative cells are the crucial cell type mediating proliferation of E. multilocularis, and most likely also E. granulosus, within host organs and should also be responsible for parasite recurrence upon discontinuation of chemotherapy.,Interestingly, recent investigations have also indicated that germinative cells might be less sensitive to chemotherapy because they express a beta-tubulin isoform with limited affinity to benzimidazoles.,In this article, we briefly review the recent findings concerning Echinococcus genomics and stem cell research and propose that future research into anti-echinococcosis drugs should also focus on the parasite’s stem cell population.

Cystic Echinococosis (CE) is a zoonotic disease caused by larval stage Echinococcus granulosus.,We determined the effects of high dose of Oxfendazole (OXF), combination Oxfendazole/Praziquantel (PZQ), and combination Albendazole (ABZ)/Praziquantel against CE in sheep.,A randomized placebo-controlled trial was carried out on 118 randomly selected ewes.,They were randomly assigned to one of the following groups: 1) placebo; 2) OXF 60 mg/Kg of body weight (BW) weekly for four weeks; 3) ABZ 30 mg/Kg BW + PZQ 40 mg/Kg BW weekly for 6 weeks, and 4) OXF 30 mg/Kg BW+ PZQ 40 mg/Kg BW biweekly for 3 administrations (6 weeks).,Percent protoscolex (PSC) viability was evaluated using a 0.1% aqueous eosin vital stain for each cyst.,“Noninfective” sheep were those that had no viable PSCs; “low-medium infective” were those that had 1% to 60% PSC viability; and “high infective” were those with more than 60% PSC viability.,We evaluated 92 of the 118 sheep.,ABZ/PZQ led the lowest PSC viability for lung cysts (12.7%), while OXF/PZQ did so for liver cysts (13.5%).,The percentage of either “noninfective” or “low-medium infective” sheep was 90%, 93.8% and 88.9% for OXF, ABZ/PZQ and OXF/PZQ group as compared to 50% “noninfective” or “low-medium infective” for placebo.,After performing all necropsies, CE prevalence in the flock of sheep was 95.7% (88/92) with a total number of 1094 cysts (12.4 cysts/animal).,On average, the two-drug-combination groups resulted pulmonary cysts that were 6 mm smaller and hepatic cysts that were 4.2 mm smaller than placebo (p<0.05).,We demonstrate that Oxfendazole at 60 mg, combination Oxfendazole/Praziquantel and combination Albendazole/Praziquantel are successful schemas that can be added to control measures in animals and merits further study for the treatment of animal CE.,Further investigations on different schedules of monotherapy or combined chemotherapy are needed, as well as studies to evaluate the safety and efficacy of Oxfendazole in humans.

Integration of disease-specific programmes into the primary health care (PHC) service has been attempted mostly in clinically oriented disease control such as HIV/AIDS and tuberculosis but rarely in vector control.,Chagas disease is controlled principally by interventions against the triatomine vector.,In Honduras, after successful reduction of household infestation by vertical approach, the Ministry of Health implemented community-based vector surveillance at the PHC services (health centres) to prevent the resurgence of infection.,This paper retrospectively analyses the effects and process of integrating a Chagas disease vector surveillance system into health centres.,We evaluated the effects of integration at six pilot sites in western Honduras during 2008-2011 on; surveillance performance; knowledge, attitude and practice in schoolchildren; reports of triatomine bug infestation and institutional response; and seroprevalence among children under 15 years of age.,The process of integration of the surveillance system was analysed using the PRECEDE-PROCEED model for health programme planning.,The model was employed to systematically determine influential and interactive factors which facilitated the integration process at different levels of the Ministry of Health and the community.,Overall surveillance performance improved from 46 to 84 on a 100 point-scale.,Schoolchildren’s attitude (risk awareness) score significantly increased from 77 to 83 points.,Seroprevalence declined from 3.4% to 0.4%.,Health centres responded to the community bug reports by insecticide spraying.,As key factors, the health centres had potential management capacity and influence over the inhabitants’ behaviours and living environment directly and through community health volunteers.,The National Chagas Programme played an essential role in facilitating changes with adequate distribution of responsibilities, participatory modelling, training and, evaluation and advocacy.,We found that Chagas disease vector surveillance can be integrated into the PHC service.,Health centres demonstrated capacity to manage vector surveillance and improve performance, children’s awareness, vector report-response and seroprevalence, once tasks were simplified to be performed by trained non-specialists and distributed among the stakeholders.,Health systems integration requires health workers to perform beyond their usual responsibilities and acquire management skills.,Integration of vector control is feasible and can contribute to strengthening the preventive capacity of the PHC service.

Chagas disease control campaigns relying upon residual insecticide spraying have been successful in many Southern American countries.,However, in some areas, rapid reinfestation and recrudescence of transmission have occurred.,We conducted a cross-sectional survey in the Bolivian Chaco to evaluate prevalence of and risk factors for T. cruzi infection 11 years after two rounds of blanket insecticide application.,We used a cubic B-spline model to estimate change in force of infection over time based on age-specific seroprevalence data.,Overall T. cruzi seroprevalence was 51.7%.,The prevalence was 19.8% among children 2-15, 72.7% among those 15-30 and 97.1% among participants older than 30 years.,Based on the model, the estimated annual force of infection was 4.3% over the two years before the first blanket spray in 2000 and fell to 0.4% for 2001-2002.,The estimated annual force of infection for 2004-2005, the 2 year period following the second blanket spray, was 4.6%.,However, the 95% bootstrap confidence intervals overlap for all of these estimates.,In a multivariable model, only sleeping in a structure with cracks in the walls (aOR = 2.35; 95% CI = 1.15-4.78), age and village of residence were associated with infection.,As in other areas in the Chaco, we found an extremely high prevalence of Chagas disease.,Despite evidence that blanket insecticide application in 2000 may have decreased the force of infection, active transmission is ongoing.,Continued spraying vigilance, infestation surveillance, and systematic household improvements are necessary to disrupt and sustain interruption of infection transmission.

Plasmodium parasites undergo a clinically silent and obligatory developmental phase in the host’s liver cells before they are able to infect erythrocytes and cause malaria symptoms.,To overcome the scarcity of compounds targeting the liver stage of malaria, we screened a library of 1037 existing drugs for their ability to inhibit Plasmodium hepatic development.,Decoquinate emerged as the strongest inhibitor of Plasmodium liver stages, both in vitro and in vivo.,Furthermore, decoquinate kills the parasite’s replicative blood stages and is active against developing gametocytes, the forms responsible for transmission.,The drug acts by selectively and specifically inhibiting the parasite’s mitochondrial bc1 complex, with little cross-resistance with the antimalarial drug atovaquone.,Oral administration of a single dose of decoquinate effectively prevents the appearance of disease, warranting its exploitation as a potent antimalarial compound.

Doxycycline, a synthetically derived tetracycline, is a partially efficacious causal prophylactic (liver stage of Plasmodium) drug and a slow acting blood schizontocidal agent highly effective for the prevention of malaria.,When used in conjunction with a fast acting schizontocidal agent, it is also highly effective for malaria treatment.,Doxycycline is especially useful as a prophylaxis in areas with chloroquine and multidrug-resistant Plasmodium falciparum malaria.,Although not recommended for pregnant women and children < 8 years of age, severe adverse events are rarely reported for doxycycline.,This report examines the evidence behind current recommendations for the use of doxycycline for malaria and summarizes the available literature on its safety and tolerability.

Efforts to control Schistosoma mansoni infection depend on the ability of programs to effectively detect and quantify infection levels and adjust programmatic approaches based on these levels and program goals.,One of the three major objectives of the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) has been to develop and/or evaluate tools that would assist Neglected Tropical Disease program managers in accomplishing this fundamental task.,The advent of a widely available point-of-care (POC) assay to detect schistosome circulating cathodic antigen (CCA) in urine with a rapid diagnostic test (the POC-CCA) in 2008 led SCORE and others to conduct multiple evaluations of this assay, comparing it with the Kato-Katz (KK) stool microscopy assay-the standard used for more than 45 years.,This article describes multiple SCORE-funded studies comparing the POC-CCA and KK assays, the pros and cons of these assays, the use of the POC-CCA assay for mapping of S. mansoni infections in areas across the spectrum of prevalence levels, and the validation and recognition that the POC-CCA, although not infallible, is a highly useful tool to detect low-intensity infections in low-to-moderate prevalence areas.,Such an assay is critical, as control programs succeed in driving down prevalence and intensity and seek to either maintain control or move to elimination of transmission of S. mansoni.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in late 2008 to conduct operational research to inform global health practices related to the control and elimination of schistosomiasis.,The greatest part of the SCORE investment has been in multiyear, long-term efforts, including cluster-randomized trials of gaining and sustaining control of schistosomiasis, trials on elimination of schistosomiasis, and diagnostic test development and evaluation.,In the course of planning and conducting SCORE studies, critical questions were raised that could be answered relatively quickly by collecting, collating, and synthesizing existing data.,Through its Rapid Answers Project (RAP), the SCORE conducted seven systematic reviews, including four associated meta-analyses, on issues related to screening for schistosomiasis, enhancing mass drug administration, treatment impacts, and the efficacy of snail control for prevention of human schistosomiasis.,This article summarizes the findings of the seven RAP reports and provides links to the studies and their supporting information.

In epidemiological surveys and surveillance the application of molecular tools is essential in detecting submicroscopic malaria.,A genus-specific conventional cytochrome b (cytb) PCR has shown high sensitivity in field studies, detecting 70% submicroscopic malaria.,The main objective of this study was to assess the conversion from conventional to real-time PCR testing both SYBR and probe protocols, and including quantitative (q) PCR.,The protocols were assessed applying well-defined clinical patient material consisting of 33 positive and 80 negative samples.,Sequencing of positive PCR products was performed.,In addition, a sensitivity comparison of real-time PCR methods was done by including five relevant assays investigating the effect of amplification target and platform.,Sensitivity was further examined using field material consisting of 111 P.falciparum positive samples from Tanzanian children (< 5 years), as well as using related patient data to assess the application of q-PCR with focus on low-level parasitaemia.,Both the cytb SYBR and probe PCR protocols showed as high sensitivity and specificity as their conventional counterpart, except missing one P. malariae sample.,The SYBR protocol was more sensitive and specific than using probe.,Overall, choice of amplification target applied is relevant for achieving ultra-sensitivity, and using intercalating fluorescence dye rather than labelled hydrolysis probes is favourable.,Application of q-PCR analysis in field projects is important for the awareness and understanding of low-level parasitaemia.,For use in clinical diagnosis and epidemiological studies the highly sensitive and user-friendly cytb SYBR q-PCR method is a relevant tool.,The genus-specific method has the advantage that species identification by sequencing can be performed as an alternative to species-specific PCR.

As malaria transmission continues to decrease, an increasing number of countries will enter pre-elimination and elimination.,To interrupt transmission, changes in control strategies are likely to require more accurate identification of all carriers of Plasmodium parasites, both symptomatic and asymptomatic, using diagnostic tools that are highly sensitive, high throughput and with fast turnaround times preferably performed in local health service settings.,Currently available immunochromatographic lateral flow rapid diagnostic tests and field microscopy are unlikely to consistently detect infections at parasite densities less than 100 parasites/µL making them insufficiently sensitive for detecting all carriers.,Molecular diagnostic platforms, such as PCR and LAMP, are currently available in reference laboratories, but at a cost both financially and in turnaround time.,This review describes the recent progress in developing molecular diagnostic tools in terms of their capacity for high throughput and potential for performance in non-reference laboratories for malaria elimination.

Tengchong County experienced a decreasing malaria prevalence period in 2005-2014 but the factors contributing to the trend are unclear.,Herein, the malaria epidemiological data in years of 2005-2014 were collected and analysed, in order to provide evidence for subsequent effective strategic planning of malaria elimination that may be referenced by other counties with the similar elimination programmes along the China-Myanmar border.,A retrospective study was conducted to explore malaria-endemic characteristics in years 2005-2014 in Tengchong County.,All individual cases from a web-based reporting system were reviewed and analysed.,Local infections and imported cases were obtained from an annual reporting system.,In total, 8321 confirmed malaria cases were recorded in this period, and 91.5 % of them were reported during 2005-2010.,Plasmodium vivax was the major species (n = 5867, 70.5 %).,Most cases (92.9 %) were found in males, mainly in the age group 30-34 years.,Only five deaths resulting from Plasmodium falciparum were reported, of which three occurred in 2005.,The cases were mainly reported in the townships of Wuhe (18.5 %), Mangbang (12.8 %) and Gudong (9.3 %).,In addition, 147 local malaria (1.8 %) and 8174 imported malaria (98.2 %) were observed during 2005-2014.,However, the proportion of imported malaria was more than 95 % all the time and no local transmission has been observed since 2013.,Moreover, Myanmar was the main imported source, with 716 cases (94.6 %, 716/757) from Myanmar in 2011-2014.,Tengchong County has made achievements in controlling malaria, with incidence at historically its lowest level.,However, imported malaria has increased and poses a great threat to malaria elimination.,To achieve the elimination goal and prevent the re-introduction of malaria, surveillance systems need to be well planned and managed to ensure timely case detection and prompt response targeted to the mobile and migrate population at elimination stage.

The parasites that cause malaria depend on Anopheles mosquitoes for transmission; because of this, mosquito population dynamics are a key determinant of malaria risk.,Development and survival rates of both the Anopheles mosquitoes and the Plasmodium parasites that cause malaria depend on temperature, making this a potential driver of mosquito population dynamics and malaria transmission.,We developed a temperature-dependent, stage-structured delayed differential equation model to better understand how climate determines risk.,Including the full mosquito life cycle in the model reveals that the mosquito population abundance is more sensitive to temperature than previously thought because it is strongly influenced by the dynamics of the juvenile mosquito stages whose vital rates are also temperature-dependent.,Additionally, the model predicts a peak in abundance of mosquitoes old enough to vector malaria at more accurate temperatures than previous models.,Our results point to the importance of incorporating detailed vector biology into models for predicting the risk for vector borne diseases.

In our previous work, a Trichinella spiralis putative serine protease (TsSP) was identified from ES products of T. spiralis intestinal infective larvae (IIL) and adult worms (AW) by immunoproteomics: it was highly expressed in IIL compared with muscle larvae (ML).,In this study, the TsSP biological characteristics in larval invasion and growth were identified and its potential as a vaccine target against Trichinella infection were investigated.,Expression of TsSP at various developmental phases (newborn larvae, ML, IIL, and AW) was detected by qPCR, immunofluorescent test and Western blotting.,The rTsSP could specifically bind to the intestinal epithelial cell (IEC) membrane and enter into the cytoplasm.,Anti-rTsSP serum suppressed the larval invasion of enterocytes in a dose-dependent mode, and killed newborn and ML of T. spiralis, decreased larval infectivity and development in the host by an ADCC-mediated mechanism.,Immunization of mice with rTsSP produced a Th2 predominant immune response, and resulted in a 52.70% reduction of adult worms at 5 days post-infection (dpi) and a 52.10% reduction of muscle larvae at 42 dpi.,The results revealed there was an interaction between TsSP and the host’s IEC; TsSP might be a pivotal protein for the invading, growing and parasiting of this nematode in the host.,Vaccination of mice with rTsSP elicited immune protection, and TsSP is a potential target molecule for vaccines against enteral Trichinella infection.

Trichinellosis is a serious zoonositc parasitosis worldwide.,Because its clinical manifestations aren’t specific, the diagnosis of trichinellosis is not easy to be made.,Trichinella spiralis muscle larva (ML) excretory-secretory (ES) antigens are the most widely applied diagnostic antigens for human trichinellosis, but the major drawback of the ES antigens for assaying anti-Trichinella antibodies is the false negative in the early Trichinella infection period.,The aim of this study was to characterize the T. spiralis putative serine protease (TsSP) and to investigate its potential use for diagnosis of trichinellosis.,The full-length TsSP sequence was cloned and expressed, and recombinant TsSP (rTsSP) was purified by Ni-NTA-Sefinose Column.,On Western blotting analysis the rTsSP was recognized by T. spiralis-infected mouse serum, and the natural TsSP was identified in T. spiralis ML crude and ES antigens by using anti-rTsSP serum.,Expression of TsSP was detected at various T. spiralis developmental stages (newborn larvae, muscle larvae, intestinal infective larvae and adult worms).,Immunolocalization identified the TsSP principally in cuticles and stichosomes of the nematode.,The sensitivity of rTsSP-ELISA and ES-ELISA was 98.11% (52/53) and 88.68% (47/53) respectively (P > 0.05) when the sera from trichinellosis patients were examined.,However, while twenty-one serum samples of trichinellosis patients’ sera at 19 days post-infection (dpi) were tested, the sensitivity (95.24%) of rTsSP-ELISA was distinctly higher than 71.43% of ES-ELISA (P < 0.05).,The specificity (99.53%) of rTsSP-ELISA was remarkably higher than 91.98% of ES-ELISA (P < 0.01).,Only one out of 20 serum samples of cysticercosis patients cross-reacted with the rTsSP.,Specific anti-Trichinella IgG in infected mice was first detected by rTsSP-ELISA as soon as 7 dpi and antibody positive rate reached 100% on 10 dpi, whereas the ES-ELISA did not permit detection of 100% of infected mice before 16 dpi.,The rTsSP is a potential early diagnostic antigen for human trichinellosis.

Chagas disease, caused by Trypanosoma cruzi, is the main cause of dilated cardiomyopathy in the Americas.,Antiparasitic treatment mostly relies on benznidazole (Bzl) due to Nifurtimox shortage or unavailability.,Both induce adverse drug effects (ADE) of varied severity in many patients, leading to treatment discontinuation or abandonment.,Since dosage may influence ADE, we aimed to assess Bzl efficacy in terms of parasiticidal and anti-inflammatory activity, using doses lower than those previously reported.,BALB/c mice infected with the T. cruzi RA strain were treated with different doses of Bzl.,Parasitaemia, mortality and weight change were assessed.,Parasite load, tissue infiltrates and inflammatory mediators were studied in the heart.,Serum creatine kinase (CK) activity was determined as a marker of heart damage.,The infection-independent anti-inflammatory properties of Bzl were studied in an in vitro model of LPS-treated cardiomyocyte culture.,Treatment with 25 mg/kg/day Bzl turned negative the parasitological parameters, induced a significant decrease in IL-1β, IL-6 and NOS2 in the heart and CK activity in serum, to normal levels.,No mortality was observed in infected treated mice.,Primary cultured cardiomyocytes treated with Bzl showed that inflammatory mediators were reduced via inhibition of the NF-κB pathway.,A Bzl dose lower than that previously reported for treatment of experimental Chagas disease exerts adequate antiparasitic and anti-inflammatory effects leading to parasite clearance and tissue healing.,This may be relevant to reassess the dose currently used for the treatment of human Chagas disease, aiming to minimize ADE.,•Benznidazole is effective as an antiparasitic drug at a dose lower than the usual one.,•NOS2 and pro-inflammatory cytokines are inhibited by low dose of benznidazole.,•Benznidazole at low concentrations inhibits NF-κB pathway in cultured cardiomyocytes.,Benznidazole is effective as an antiparasitic drug at a dose lower than the usual one.,NOS2 and pro-inflammatory cytokines are inhibited by low dose of benznidazole.,Benznidazole at low concentrations inhibits NF-κB pathway in cultured cardiomyocytes.

The nitroheterocyclic drugs nifurtimox and benznidazole are first-line drugs available to treat Chagas disease; however, they have limitations, including long treatment courses and toxicity.,Strategies to overcome these limitations include the identification of new drugs with specific target profiles, re-dosing regimens for the current drugs, drug repositioning and combination therapy.,In this work, we evaluated combination therapy as an approach for optimization of the current therapeutic regimen for Chagas disease.,The curative action of benznidazole/itraconazole combinations was explored in an established infection of the mice model with the T. cruzi Y strain.,The activities of the benznidazole/itraconazole combinations were compared with the results from those receiving the same dosage of each individual drug.,The administration of benznidazole/itraconazole in combination eliminated parasites from the blood more efficiently than each drug alone.,Here, there was a significant reduction of the number of treatment days (number of doses) necessary to induce parasitemia suppression with the benznidazole/itraconazole combination, as compared to each compound administered alone.,These results clearly indicate the enhanced effects of these drugs in combination, particularly at the dose of 75 mg/kg, as the effects observed with the drug combinations were four times more effective than those of each drug used alone.,Moreover, benznidazole/itraconazole treatment was shown to prevent or decrease the typical lesions associated with chronic experimental Chagas disease, as illustrated by similar levels of inflammatory cells and fibrosis in the cardiac muscle tissue of healthy and treated mice.,These results emphasize the importance of exploring the potential of combination treatments with currently available compounds to specifically treat Chagas disease.

WHO’s Global Programme to Eliminate Lymphatic Filariasis (LF) uses mass drug administration (MDA) of anthelmintic medications to interrupt LF transmission in endemic areas.,Recently, a single dose combination of ivermectin (IVM), diethylcarbamazine (DEC), and albendazole (ALB) was shown to be markedly more effective than the standard two-drug regimens (DEC or IVM, plus ALB) for achieving long-term clearance of microfilaremia.,To provide context for the results of a large-scale, international safety trial of MDA using triple drug therapy, we searched Ovid Medline for studies published from 1985-2017 that reported adverse events (AEs) following treatment of LF with IVM, DEC, ALB, or any combination of these medications.,Studies that reported AE rates by treatment group were included.,We reviewed 162 published manuscripts, 55 of which met inclusion criteria.,Among these, 34 were clinic or hospital-based clinical trials, and 21 were community-based studies.,Reported AE rates varied widely.,The median AE rate following DEC or IVM treatment was greater than 60% among microfilaremic participants and less than 10% in persons without microfilaremia.,The most common AEs reported were fever, headache, myalgia or arthralgia, fatigue, and malaise.,Mild to moderate systemic AEs related to death of microfilariae are common following LF treatment.,Post-treatment AEs are transient and rarely severe or serious.,Comparison of AE rates from different community studies is difficult due to inconsistent AE reporting, varied infection rates, and varied intensity of follow-up.,A more uniform approach for assessing and reporting AEs in LF community treatment studies would be helpful.

Globally, 40 million people live with the chronic effects of lymphatic filariasis (LF), making it the second leading cause of disability in the world.,Despite this, there is limited research into the experiences of people living with the disease.,This review summarises the research on the experiences of people living with LF disability.,The review highlights the widespread social stigma and oppressive psychological issues that face most people living with LF-related disability.,Physical manifestations of LF make daily activities and participation in community life difficult.,The findings confirm the need for the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to support morbidity management activities that address the complex biopsychosocial issues that people living with LF-related disability face.

Plasmodium vivax has been recently discovered as a significant cause of malaria in Mauritania, although very rare elsewhere in West Africa.,It has not been known if this is a recently introduced or locally remnant parasite population, nor whether the genetic structure reflects epidemic or endemic transmission.,To investigate the P. vivax population genetic structure in Mauritania and compare with populations previously analysed elsewhere, multi-locus genotyping was undertaken on 100 clinical isolates, using a genome-wide panel of 38 single nucleotide polymorphisms (SNPs), plus seven SNPs in drug resistance genes.,The Mauritanian P. vivax population is shown to be genetically diverse and divergent from populations elsewhere, indicated consistently by genetic distance matrix analysis, principal components analyses, and fixation indices.,Only one isolate had a genotype clearly indicating recent importation, from a southeast Asian source.,There was no linkage disequilibrium in the local parasite population, and only a small number of infections appeared to be closely genetically related, indicating that there is ongoing genetic recombination consistent with endemic transmission.,The P. vivax diversity in a remote mining town was similar to that in the capital Nouakchott, with no indication of local substructure or of epidemic population structure.,Drug resistance alleles were virtually absent in Mauritania, in contrast with P. vivax in other areas of the world.,The molecular epidemiology indicates that there is long-standing endemic transmission that will be very challenging to eliminate.,The virtual absence of drug resistance alleles suggests that most infections have been untreated, and that this endemic infection has been more neglected in comparison to P. vivax elsewhere.

Plasmodium vivax shows a small prevalence in West and Central Africa due to the high prevalence of Duffy negative people.,However, Duffy negative individuals infected with P. vivax have been reported in areas of high prevalence of Duffy positive people who may serve as supply of P. vivax strains able to invade Duffy negative erythrocytes.,We investigated the presence of P. vivax in two West African countries, using blood samples and mosquitoes collected during two on-going studies.,Blood samples from a total of 995 individuals were collected in seven villages in Angola and Equatorial Guinea, and 820 Anopheles mosquitoes were collected in Equatorial Guinea.,Identification of the Plasmodium species was achieved by nested PCR amplification of the small-subunit rRNA genes; P. vivax was further characterized by csp gene analysis.,Positive P. vivax-human isolates were genotyped for the Duffy blood group through the analysis of the DARC gene.,Fifteen Duffy-negative individuals, 8 from Equatorial Guinea (out of 97) and 7 from Angola (out of 898), were infected with two different strains of P. vivax (VK210 and VK247).,In this study we demonstrated that P. vivax infections were found both in humans and mosquitoes, which means that active transmission is occurring.,Given the high prevalence of infection in mosquitoes, we may speculate that this hypnozoite-forming species at liver may not be detected by the peripheral blood samples analysis.,Also, this is the first report of Duffy negative individuals infected with two different strains of P. vivax (VK247 and classic strains) in Angola and Equatorial Guinea.,This finding reinforces the idea that this parasite is able to use receptors other than Duffy to invade erythrocytes, which may have an enormous impact in P. vivax current distribution.

It is estimated that around 52,000 people live with Chagas in Spain, but only 10% have been diagnosed.,Migrants from Bolivia bear the burden of Chagas infection in Spain.,However, little is known about their current management of Chagas diagnosis and treatment patterns.,This study aimed to assess the Chagas related disease perception and health behaviour of Bolivians living in Madrid.,For a first time, a cross-sectional survey about Chagas’ knowledges and practices was carried out in Madrid, Spain.,A total of 376 Bolivians were interviewed about their Chagas health-seeking behaviour.,Differences between men and women were assessed Most of Bolivians living in Madrid have access to the public health services. 44% of Bolivians included in the survey had a Chagas screening test done.,However, while women did their test for Chagas mostly at hospital (59.2%), men also used the community campaigns (17.5%) and blood banks (14.3%).,The prevalence reported among Bolivians tested was 27.7%.,Unfortunately, more than half of those reporting a positive test for Chagas did not begin or completed treatment.,Only 45.7% of positives reported having had their children tested for Chagas.,Despite the increase in the number of Chagas diagnoses done in Madrid, the number of Bolivians who tested positive and then started or completed treatment remains very low.,The fact that most Bolivians’ access to the health system is through the primary healthcare services should be considered for improving management of cases and follow-up of treatment adherence.,Local and national protocol establishing guidelines for the screening and treatment of Chagas disease would help improving case detection and management at all levels of the healthcare system.

Chagas disease prevention remains mostly based on triatomine vector control to reduce or eliminate house infestation with these bugs.,The level of adaptation of triatomines to human housing is a key part of vector competence and needs to be precisely evaluated to allow for the design of effective vector control strategies.,In this review, we examine how the domiciliation/intrusion level of different triatomine species/populations has been defined and measured and discuss how these concepts may be improved for a better understanding of their ecology and evolution, as well as for the design of more effective control strategies against a large variety of triatomine species.,We suggest that a major limitation of current criteria for classifying triatomines into sylvatic, intrusive, domiciliary and domestic species is that these are essentially qualitative and do not rely on quantitative variables measuring population sustainability and fitness in their different habitats.,However, such assessments may be derived from further analysis and modelling of field data.,Such approaches can shed new light on the domiciliation process of triatomines and may represent a key tool for decision-making and the design of vector control interventions.

In a low-endemicity/malaria elimination setting, we demonstrate limited sensitivity of Plasmodium falciparum-specific rapid diagnostic testing for suspected malaria, owing to unexpected low-density infections.,Positive predictive value was also low, requiring further investigation.,More accurate diagnostics may be needed.,The performance of Plasmodium falciparum-specific histidine-rich protein 2-based rapid diagnostic tests (RDTs) to evaluate suspected malaria in low-endemicity settings has not been well characterized.,Using dried blood spot samples from patients with suspected malaria at 37 health facilities from 2012 to 2014 in the low-endemicity country of Swaziland, we investigated the diagnostic accuracy of histidine-rich protein 2-based RDTs using qualitative polymerase chain reaction (PCR) (nested PCR targeting the cytochrome b gene) and quantitative PCR as reference standards.,To explore reasons for false-negative and/or false-positive results, we used pfhrp2/3-specific PCR and logistic regression analyses of potentially associated epidemiological factors.,From 1353 patients, 93.0% of RDT-positive (n = 185) and 31.2% of RDT-negative samples (n = 340) were available and selected for testing.,Compared with nested PCR, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RDTs were 51.7%, 94.1%, 67.3%, and 89.1%, respectively.,After exclusion of samples with parasite densities <100/μL, which accounted for 75.7% of false-negative results and 33.3% of PCR-detectable infections, the sensitivity, specificity, PPV, and NPV were 78.8%, 93.7%, 62.3%, and 97.1%.,Deletions of pfhrp2 were not detected.,False-positivity was more likely during the second year and was not associated with demographics, recent malaria, health facility testing characteristics, or potential DNA degradation.,In the low-transmission setting of Swaziland, we demonstrated low sensitivity of RDT for malaria diagnosis, owing to an unexpectedly high proportion of low-density infection among symptomatic subjects.,The PPV was also low, requiring further investigation.,A more accurate point-of-care diagnostic may be needed to support malaria elimination efforts.

Rapid diagnostic tests (RDTs) detecting histidine-rich protein 2 (PfHRP2) antigen are used to identify individuals with Plasmodium falciparum infection even in low transmission settings seeking to achieve elimination.,However, these RDTs lack sensitivity to detect low-density infections, produce false negatives for P. falciparum strains lacking pfhrp2 gene and do not detect species other than P. falciparum.,Results of a PfHRP2-based RDT and Plasmodium nested PCR were compared in a region of declining malaria transmission in southern Zambia using samples from community-based, cross-sectional surveys from 2008 to 2012.,Participants were tested with a PfHRP2-based RDT and a finger prick blood sample was spotted onto filter paper for PCR analysis and used to prepare blood smears for microscopy.,Species-specific, real-time, quantitative PCR (q-PCR) was performed on samples that tested positive either by microscopy, RDT or nested PCR.,Of 3,292 total participants enrolled, 12 (0.4%) tested positive by microscopy and 42 (1.3%) by RDT.,Of 3,213 (98%) samples tested by nested PCR, 57 (1.8%) were positive, resulting in 87 participants positive by at least one of the three tests.,Of these, 61 tested positive for P. falciparum by q-PCR with copy numbers ≤ 2 x 103 copies/μL, 5 were positive for both P. falciparum and Plasmodium malariae and 2 were positive for P. malariae alone.,RDT detected 32 (53%) of P. falciparum positives, failing to detect three of the dual infections with P. malariae.,Among 2,975 participants enrolled during a low transmission period between 2009 and 2012, sensitivity of the PfHRP2-based RDT compared to nested PCR was only 17%, with specificity of >99%.,The pfhrp gene was detected in 80% of P. falciparum positives; however, comparison of copy number between RDT negative and RDT positive samples suggested that RDT negatives resulted from low parasitaemia and not pfhrp2 gene deletion.,Low-density P. falciparum infections not identified by currently used PfHRP2-based RDTs and the inability to detect non-falciparum malaria will hinder progress to further reduce malaria in low transmission settings of Zambia.,More sensitive and specific diagnostic tests will likely be necessary to identify parasite reservoirs and achieve malaria elimination.,The online version of this article (doi:10.1186/s12936-015-0544-3) contains supplementary material, which is available to authorized users.

Determination of the genetic diversity of malaria parasites can inform the intensity of transmission and identify potential deficiencies in malaria control programmes.,This study was conducted to characterize the genetic diversity and allele frequencies of Plasmodium falciparum in Northwest Ethiopia along the Eritrea and Sudan border.,A total of 90 isolates from patients presenting to the local health centre with uncomplicated P. falciparum were collected from October 2014 to January 2015.,DNA was extracted and the polymorphic regions of the msp-1, msp-2 and glurp loci were genotyped by nested polymerase chain reactions followed by gel electrophoresis for fragment analysis.,Allelic variation in msp-1, msp-2 and glurp were identified in 90 blood samples.,A total of 34 msp alleles (12 for msp-1 and 22 for msp-2) were detected.,For msp-1 97.8% (88/90), msp-2 82.2% (74/90) and glurp 46.7% (42/90) were detected.,In msp-1, MAD20 was the predominant allelic family detected in 47.7% (42/88) of the isolates followed by RO33 and K1.,For msp-2, the frequency of FC27 and IC/3D7 were 77% (57/74) and 76% (56/74), respectively.,Nine glurp RII region genotypes were identified.,Seventy percent of isolates had multiple genotypes and the overall mean multiplicity of infection was 2.6 (95% CI 2.25-2.97).,The heterozygosity index was 0.82, 0.62 and 0.20 for msp-1, msp-2 and glurp, respectively.,There was no significant association between multiplicity of infection and age or parasite density.,There was a high degree of genetic diversity with multiple clones in P. falciparum isolates from Northwest Ethiopia suggesting that there is a need for improved malaria control efforts in this region.,The online version of this article (10.1186/s12936-018-2540-x) contains supplementary material, which is available to authorized users.

Members of the Anopheles gambiae (s.l.) complex are one of the major vectors of malaria in Africa.,LLINs and IRS are the most effective tools used in vector control of malaria.,However, their effectiveness may be hampered by the development and spread of insecticide resistance in the target vectors species.,The objective of this study was to assess the susceptibility of Anopheles gambiae (s.l.) mosquitoes from South-West Cameroon to deltamethrin, permethrin and to malathion, four years after the mass deployment of LLINs.,Anopheles larvae were collected from Limbe, Tiko and Buea, three cities of the Fako division and reared until adult emergence.,Adult mosquitoes from field larvae were identified as belonging to the Anopheles gambiae (s.l.) complex using standard identification keys.,Susceptibility of mosquito samples to deltamethrin, permethrin and malathion was assessed using WHO susceptibility tests protocol for adult mosquitoes.,Molecular identification of tested samples was performed using the PCR SINE200 protocol and by PCR-RFLP.,The kdr alleles were genotyped using the hot ligation oligonucleotide assay (HOLA).,Two species of the An. gambiae (s.l.) complex, An. coluzzii and An. gambiae (s.s.) were identified in all three study locations with high proportions of An. coluzzii in Limbe (84.06%) and Tiko (92.2%), while in Buea, An. coluzzii (55.6%) and An. gambiae (s.s.),(44.4%) occurred almost in the same proportions.,Tested samples were found resistant to pyrethroids (deltamethrin and permethrin) in all locations (< 90% mortality), with > 3-fold increase of KDT50 values compared with the Kisumu susceptible reference strain of An. gambiae (s.s.).,However, the mosquito populations from Limbe and Buea were fully susceptible to malathion.,The L1014F kdr was found in both An. coluzzii and An. gambiae (s.s.) with the highest frequencies found in An. gambiae (s.l.) populations from Tiko (94%) and Buea (90%) compared with the Limbe population (66%) (P = 0.00063, df = 2).,No kdr L1014S was observed in analyzed samples.,These findings reemphasize the ongoing development of An. gambiae (s.l.) resistance to pyrethroids used in impregnating LLINs and suggest the use of malathion as an alternative insecticide for IRS in complementarity with LLINs.,The online version of this article (10.1186/s13071-018-2979-1) contains supplementary material, which is available to authorized users.

Malaria risk stratification is essential to differentiate areas with distinct malaria intensity and seasonality patterns.,The development of a simple prediction model to forecast malaria incidence by rainfall offers an opportunity for early detection of malaria epidemics.,To construct a national malaria stratification map, develop prediction models and forecast monthly malaria incidences based on rainfall data.,Using monthly malaria incidence data from 2012 to 2016, the district level malaria stratification was constructed by nonhierarchical clustering.,Cluster validity was examined by the maximum absolute coordinate change and analysis of variance (ANOVA) with a conservative post hoc test (Bonferroni) as the multiple comparison test.,Autocorrelation and cross-correlation analyses were performed to detect the autocorrelation of malaria incidence and the lagged effect of rainfall on malaria incidence.,The effect of rainfall on malaria incidence was assessed using seasonal autoregressive integrated moving average (SARIMA) models.,Ljung-Box statistics for model diagnosis and stationary R-squared and Normalized Bayesian Information Criteria for model fit were used.,Model validity was assessed by analyzing the observed and predicted incidences using the spearman correlation coefficient and paired samples t-test.,A four cluster map (high risk, moderate risk, low risk, and very low risk) was the most valid stratification system for the reported malaria incidence in Eritrea.,Monthly incidences were influenced by incidence rates in the previous months.,Monthly incidence of malaria in the constructed clusters was associated with 1, 2, 3, and 4 lagged months of rainfall.,The constructed models had acceptable accuracy as 73.1%, 46.3%, 53.4%, and 50.7% of the variance in malaria transmission were explained by rainfall in the high-risk, moderate-risk, low-risk, and very low-risk clusters, respectively.,Change in rainfall patterns affect malaria incidence in Eritrea.,Using routine malaria case reports and rainfall data, malaria incidences can be forecasted with acceptable accuracy.,Further research should consider a village or health facility level modeling of malaria incidence by including other climatic factors like temperature and relative humidity.

In Côte d’Ivoire, an estimated 767,000 disability-adjusted life years are due to malaria, placing the country at position number 14 with regard to the global burden of malaria.,Risk maps are important to guide control interventions, and hence, the aim of this study was to predict the geographical distribution of malaria infection risk in children aged <16 years in Côte d’Ivoire at high spatial resolution.,Using different data sources, a systematic review was carried out to compile and geo-reference survey data on Plasmodium spp. infection prevalence in Côte d’Ivoire, focusing on children aged <16 years.,The period from 1988 to 2007 was covered.,A suite of Bayesian geo-statistical logistic regression models was fitted to analyse malaria risk.,Non-spatial models with and without exchangeable random effect parameters were compared to stationary and non-stationary spatial models.,Non-stationarity was modelled assuming that the underlying spatial process is a mixture of separate stationary processes in each ecological zone.,The best fitting model based on the deviance information criterion was used to predict Plasmodium spp. infection risk for entire Côte d’Ivoire, including uncertainty.,Overall, 235 data points at 170 unique survey locations with malaria prevalence data for individuals aged <16 years were extracted.,Most data points (n = 182, 77.4%) were collected between 2000 and 2007.,A Bayesian non-stationary regression model showed the best fit with annualized rainfall and maximum land surface temperature identified as significant environmental covariates.,This model was used to predict malaria infection risk at non-sampled locations.,High-risk areas were mainly found in the north-central and western area, while relatively low-risk areas were located in the north at the country border, in the north-east, in the south-east around Abidjan, and in the central-west between two high prevalence areas.,The malaria risk map at high spatial resolution gives an important overview of the geographical distribution of the disease in Côte d’Ivoire.,It is a useful tool for the national malaria control programme and can be utilized for spatial targeting of control interventions and rational resource allocation.

Though malaria control initiatives have markedly reduced malaria prevalence in recent decades, global eradication is far from actuality.,Recent studies show that environmental and social heterogeneities in low-transmission settings have an increased weight in shaping malaria micro-epidemiology.,New integrated and more localized control strategies should be developed and tested.,Here we present a set of agent-based models designed to study the influence of local scale human movements on local scale malaria transmission in a typical Amazon environment, where malaria is transmission is low and strongly connected with seasonal riverine flooding.,The agent-based simulations show that the overall malaria incidence is essentially not influenced by local scale human movements.,In contrast, the locations of malaria high risk spatial hotspots heavily depend on human movements because simulated malaria hotspots are mainly centered on farms, were laborers work during the day.,The agent-based models are then used to test the effectiveness of two different malaria control strategies both designed to reduce local scale malaria incidence by targeting hotspots.,The first control scenario consists in treat against mosquito bites people that, during the simulation, enter at least once inside hotspots revealed considering the actual sites where human individuals were infected.,The second scenario involves the treatment of people entering in hotspots calculated assuming that the infection sites of every infected individual is located in the household where the individual lives.,Simulations show that both considered scenarios perform better in controlling malaria than a randomized treatment, although targeting household hotspots shows slightly better performance.

Antimalarial drugs are a powerful tool for malaria control and elimination.,Artemisinin-based combination therapies (ACTs) can reduce transmission when widely distributed in a campaign setting.,Modelling mass antimalarial campaigns can elucidate how to most effectively deploy drug-based interventions and quantitatively compare the effects of cure, prophylaxis, and transmission-blocking in suppressing parasite prevalence.,A previously established agent-based model that includes innate and adaptive immunity was used to simulate malaria infections and transmission.,Pharmacokinetics of artemether, lumefantrine, dihydroartemisinin, piperaquine, and primaquine were modelled with a double-exponential distribution-elimination model including weight-dependent parameters and age-dependent dosing.,Drug killing of asexual parasites and gametocytes was calibrated to clinical data.,Mass distribution of ACTs and primaquine was simulated with seasonal mosquito dynamics at a range of transmission intensities.,A single mass campaign with antimalarial drugs is insufficient to permanently reduce malaria prevalence when transmission is high.,Current diagnostics are insufficiently sensitive to accurately identify asymptomatic infections, and mass-screen-and-treat campaigns are much less efficacious than mass drug administrations.,Improving campaign coverage leads to decreased prevalence one month after the end of the campaign, while increasing compliance lengthens the duration of protection against reinfection.,Use of a long-lasting prophylactic as part of a mass drug administration regimen confers the most benefit under conditions of high transmission and moderately high coverage.,Addition of primaquine can reduce prevalence but exerts its largest effect when coupled with a long-lasting prophylactic.,Mass administration of antimalarial drugs can be a powerful tool to reduce prevalence for a few months post-campaign.,A slow-decaying prophylactic administered with a parasite-clearing drug offers strong protection against reinfection, especially in highly endemic areas.,Transmission-blocking drugs have only limited effects unless administered with a prophylactic under very high coverage.,The online version of this article (doi:10.1186/s12879-015-0887-y) contains supplementary material, which is available to authorized users.

PermaNet® 3.0 is a deltamethrin-treated combination long-lasting insecticidal net with the addition of synergist piperonylbutoxide (PBO) on its roof section.,It is designed to overcome the challenge posed by pyrethroid resistant vector populations against mainstream long-lasting insecticidal nets impregnated with pyrethroids only.,The objective of this study was to determine insecticide resistance status of Anopheline and Culicine mosquitoes, to evaluate the bio-efficacy of PermaNet® 3.0 nets and to assess household factors affecting the physical integrity of PermaNet® 3.0 after 3 years of use.,Insecticide susceptibility test was conducted using the WHO tube test.,Bio-activity of PermaNet® 3.0 samples was evaluated using the WHO cone bioassay.,Cross-sectional survey was conducted on 150 randomly selected households from two districts to determine household factors affecting net utilization.,One hundred fifty PermaNet® 3.0 nets were randomly collected from the community with replacement after 3 years of deployment and physical integrity of each net was assessed.,Both Anopheles gambiae sensu lato and Culex quinquefasciatus developed resistance against permethrin and deltamethrin.,However, following pre-exposure to synergist PBO the susceptibility of mosquito population increased to both permethrin (from 39% without to 92% with PBO against An. gambiae and from 28% without to 94% with PBO against Culex quinquefasciatus) and deltamethrin (from 52% without to 99% with PBO against An. gambiae and from 43% without to 98% with PBO against Culex quinquefasciatus).,Eighty percent (80%) mortality was recorded in wild population of An. gambiae s.l. exposed to unused PermaNet® 3.0, but its bioactivity subsequently declined as washing frequency increased from 0 to 20.,The PBO coated roof section of unused PermaNet® 3.0 resulted in higher mosquito mortality (100%) compared to the side panels without PBO (85%).,House structure, cooking and washing habits, and damage due to household pests were cited as determinants associated with bed net deterioration.,Bed net proportionate hole index (pHI) was ranged from 0 to 6064.,Of the 150 PermaNet® 3.0 nets assessed 80, 29 and 41 were considered as ‘good’, ‘acceptable’ and ‘too torn’, respectively.,The bio-efficacy evaluation of PermaNet® 3.0 from Jimma area, southwestern Ethiopia showed moderate efficacy against pyrethroid resistant population of An. gambiae and Culex quinquefasciatus.,Thus, NMCPs in parallel to deployment of LLINs, should implement timely insecticide resistance management and integrated vector management strategies to slowdown the evolution and further spread of insecticide resistance.,Household factors such as, housing conditions, open flame fire used for cooking and rodent attack were identified as factors contributing to the observed reduced bed net physical integrity in the study area.,Universal coverage of bed nets should be accompanied with community awareness creation and training on net utilization and handling.

Despite the availability of cost effective malaria control interventions, such as insecticide-treated bed nets (ITN), diagnosis and effective treatment of malaria, and intermittent preventive treatment during pregnancy (IPTp), the lack of equitable access and coverage affect utilization of these interventions in rural communities.,Aggregated rates of access and utilization of malaria interventions in national surveys mask substantial variations in intervention coverage.,Utilization of interventions and factors affecting utilization need investigation in rural communities.,One year of quantitative data collected from a rolling Malaria Indicator Survey (April 2015-April 2016) in Chikhwawa District, Malawi, before the ITN distribution campaign, were analysed.,Univariate analyses were used to quantify rates of ITN usage, care-seeking for fever in children aged 6-59 months and women aged 15-49 years and IPTp uptake (for women aged 15-49 years with a recent delivery).,Results were compared to national survey estimates; factors associated with these outcomes were determined using multivariate regression models.,A total of 2046 participants were included from 1328 households; 56.6% were women aged 15-49 years and 43.4% were children aged 6-59 months.,Reported ownership of at least one ITN per household and under-five children ITN use the previous night were 35.3 and 33.5% compared to 70.2 and 67.1%, respectively, in the national survey; ITN use was higher in high wealth quintile households than low quintile ones.,For participants with recent fever, 37.6 and 19.5% sought care and sought care within 24 h, respectively.,Care-seeking was lower for febrile women than febrile children [aOR, 95% CI 0.53 (0.35-0.81)].,Uptake of two and three or more doses of IPTp were 40.6 and 15.0%, respectively, among women with a pregnancy in the last 2 years.,To achieve effective malaria control, fine-scale or district-based surveillance should be used to identify and target communities requiring scaling up of interventions.,Qualitative research and a participatory community approach should be used to address behavioural factors affecting how people make use of interventions.

Human African trypanosomiasis (HAT), also known as sleeping sickness, persists as a public health problem in several sub-Saharan countries.,Evidence-based, spatially explicit estimates of population at risk are needed to inform planning and implementation of field interventions, monitor disease trends, raise awareness and support advocacy.,Comprehensive, geo-referenced epidemiological records from HAT-affected countries were combined with human population layers to map five categories of risk, ranging from “very high” to “very low,” and to estimate the corresponding at-risk population.,Approximately 70 million people distributed over a surface of 1.55 million km2 are estimated to be at different levels of risk of contracting HAT.,Trypanosoma brucei gambiense accounts for 82.2% of the population at risk, the remaining 17.8% being at risk of infection from T. b. rhodesiense.,Twenty-one million people live in areas classified as moderate to very high risk, where more than 1 HAT case per 10,000 inhabitants per annum is reported.,Updated estimates of the population at risk of sleeping sickness were made, based on quantitative information on the reported cases and the geographic distribution of human population.,Due to substantial methodological differences, it is not possible to make direct comparisons with previous figures for at-risk population.,By contrast, it will be possible to explore trends in the future.,The presented maps of different HAT risk levels will help to develop site-specific strategies for control and surveillance, and to monitor progress achieved by ongoing efforts aimed at the elimination of sleeping sickness.

Human African trypanosomiasis (HAT) has been a major public health problem in South Sudan for the last century.,Recurrent outbreaks with a repetitive pattern of responding-scaling down activities have been observed.,Control measures for outbreak response were reduced when the prevalence decreased and/or socio-political crisis erupted, leading to a new increase in the number of cases.,This paper aims to raise international awareness of the threat of another outbreak of sleeping sickness in South Sudan.,It is a review of the available data, interventions over time, and current reports on the status of HAT in South Sudan.,Since 2006, control interventions and treatments providing services for sleeping sickness have been reduced.,Access to HAT diagnosis and treatment has been considerably diminished.,The current status of control activities for HAT in South Sudan could lead to a new outbreak of the disease unless 1) the remaining competent personnel are used to train younger staff to resume surveillance and treatment in the centers where HAT activities have stopped, and 2) control of HAT continues to be given priority even when the number of cases has been substantially reduced.,Failure to implement an effective and sustainable system for HAT control and surveillance will increase the risk of a new epidemic.,That would cause considerable suffering for the affected population and would be an impediment to the socioeconomic development of South Sudan.

Funding from external agencies for malaria control in Africa has increased dramatically over the past decade resulting in substantial increases in population coverage by effective malaria prevention interventions.,This unprecedented effort to scale-up malaria interventions is likely improving child survival and will likely contribute to meeting Millennium Development Goal (MDG) 4 to reduce the < 5 mortality rate by two thirds between 1990 and 2015.,The Lives Saved Tool (LiST) model was used to quantify the likely impact that malaria prevention intervention scale-up has had on malaria mortality over the past decade (2001-2010) across 43 malaria endemic countries in sub-Saharan African.,The likely impact of ITNs and malaria prevention interventions in pregnancy (intermittent preventive treatment [IPTp] and ITNs used during pregnancy) over this period was assessed.,The LiST model conservatively estimates that malaria prevention intervention scale-up over the past decade has prevented 842,800 (uncertainty: 562,800-1,364,645) child deaths due to malaria across 43 malaria-endemic countries in Africa, compared to a baseline of the year 2000.,Over the entire decade, this represents an 8.2% decrease in the number of malaria-caused child deaths that would have occurred over this period had malaria prevention coverage remained unchanged since 2000.,The biggest impact occurred in 2010 with a 24.4% decrease in malaria-caused child deaths compared to what would have happened had malaria prevention interventions not been scaled-up beyond 2000 coverage levels.,ITNs accounted for 99% of the lives saved.,The results suggest that funding for malaria prevention in Africa over the past decade has had a substantial impact on decreasing child deaths due to malaria.,Rapidly achieving and then maintaining universal coverage of these interventions should be an urgent priority for malaria control programmes in the future.,Successful scale-up in many African countries will likely contribute substantially to meeting MDG 4, as well as succeed in meeting MDG 6 (Target 1) to halt and reverse malaria incidence by 2015.

Richard Cibulskis and colleagues present estimates of the worldwide incidence of malaria in 2009, together with a critique of different estimation methods, including those based on risk maps constructed from surveys of parasite prevalence, and those based on routine case reports compiled by health ministries.,Measuring progress towards Millennium Development Goal 6, including estimates of, and time trends in, the number of malaria cases, has relied on risk maps constructed from surveys of parasite prevalence, and on routine case reports compiled by health ministries.,Here we present a critique of both methods, illustrated with national incidence estimates for 2009.,We compiled information on the number of cases reported by National Malaria Control Programs in 99 countries with ongoing malaria transmission.,For 71 countries we estimated the total incidence of Plasmodium falciparum and P. vivax by adjusting the number of reported cases using data on reporting completeness, the proportion of suspects that are parasite-positive, the proportion of confirmed cases due to each Plasmodium species, and the extent to which patients use public sector health facilities.,All four factors varied markedly among countries and regions.,For 28 African countries with less reliable routine surveillance data, we estimated the number of cases from model-based methods that link measures of malaria transmission with case incidence.,In 2009, 98% of cases were due to P. falciparum in Africa and 65% in other regions.,There were an estimated 225 million malaria cases (5th-95th centiles, 146-316 million) worldwide, 176 (110-248) million in the African region, and 49 (36-68) million elsewhere.,Our estimates are lower than other published figures, especially survey-based estimates for non-African countries.,Estimates of malaria incidence derived from routine surveillance data were typically lower than those derived from surveys of parasite prevalence.,Carefully interpreted surveillance data can be used to monitor malaria trends in response to control efforts, and to highlight areas where malaria programs and health information systems need to be strengthened.,As malaria incidence declines around the world, evaluation of control efforts will increasingly rely on robust systems of routine surveillance.,Please see later in the article for the Editors' Summary,Malaria is a life-threatening disease caused by the Plasmodium parasite, which is transmitted to people through the bites of infected mosquitoes.,According to latest estimates from the World Health Organization (WHO), in 2009, there were 225 million cases of malaria and an estimated 781,000 deaths worldwide-most deaths occurring among children living in the WHO African Region (mainly sub-Saharan Africa).,Knowing the burden of malaria in any country is an essential component of public health planning and accurately estimating the global burden is essential to monitor progress towards the United Nations' Millennium Development Goals.,Currently, there are generally two approaches used to estimate malaria incidence:,One method uses routine surveillance reports of malaria cases compiled by national health ministries, which are analyzed to take into account some deficincies in data collection, such as incomplete reporting by health facilities, the potential for overdiagnosis of malaria among patients with fever, and the use of private health facilities or none at all.,The second method uses population-based surveys of Plasmodium prevalence and case incidence from selected locations in malaria endemic areas and then uses this information to generate risk maps and to estimate the case incidence of malaria per 1,000 population, for all of the world's malaria endemic regions.,The Malaria Atlas Project-a database of malaria epidemiology based on medical intelligence and satellite-derived climate data-uses this second method.,In order for malaria epidemiology to be as accurate as possible, an evaluation of the strengths and weaknesses of both methods is necessary.,In this study, the researchers analyzed the merits of the estimates calculated by using the different approaches, to highlight areas in which both methods need to be improved to provide better assessments of malaria control.,The researchers estimated the number of malaria cases in 2009, for each of the 99 countries with ongoing malaria transmission using a combination of the two methods.,The researchers used the first method for 56 malaria endemic countries outside the WHO African Region, and for nine African countries which had the quality of data necessary to calculate estimates using the researchers statistical model-which the researchers devised to take the upper and lower limits of case detection into account.,The researchers used the second method for 34 countries in the African Region to classify malaria risk into low-transmission and high-transmission categories, and then to derive incidence rates for populations from observational studies conducted in populations in which there were no malaria control activities.,For both methods, the researchers conducted a statistical analysis to determine the range of uncertainty.,The researchers found that using a combination of methods there was a combined total of 225 million malaria cases, in the 99 countries malaria endemic countries-the majority of cases (78%) were in the WHO African region, followed by the Southeast Asian (15%) and Eastern Mediterranean regions.,In Africa, there were 214 cases per 1,000 population, compared with 23 per 1,000 in the Eastern Mediterranean region, and 19 per 1,000 in the Southeast Asia region.,Sixteen countries accounted for 80% of all estimated cases globally-all but two countries were in the African region.,The researchers found that despite the differences between methods 1 and 2, the ratio of the upper and lower limit for country estimates was approximately the same.,Using the combined methods, the incidence of malaria was estimated to be lower than previous estimates, particularly outside of Africa.,Nevertheless the methods suggest that malaria surveillance systems currently miss the majority of cases, detecting less than 10% of those estimated to occur globally.,Although the best assessment of malaria burden and trends should rely on a combination of surveillance and survey data, accurate surveillance is the ultimate goal for malaria control programs, especially as routine surveillance has advantages for estimating case incidence, spatially and through time.,However, as the researchers have identified in this study, strengthening surveillance requires a critical evaluation of inherent errors and these errors must be adequately addressed in order to have confidence in estimates of malaria burden and trends, and therefore, the return on investments for malaria control programs.,Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001142.,This study is further discussed in a PLoS Medicine Perspective by Ivo Mueller and colleagues,The WHO provides information on malaria and produces the World Malaria Report each year, summarizing global progress in malaria control,More information is available on The Malaria Atlas Project

More than 80% of available malaria rapid diagnostic tests (RDTs) are based on the detection of histidine-rich protein-2 (PfHRP2) for diagnosis of Plasmodium falciparum malaria.,Recent studies have shown the genes that code for this protein and its paralog, histidine-rich protein-3 (PfHRP3), are absent in parasites from the Peruvian Amazon Basin.,Lack of PfHRP2 protein through deletion of the pfhrp2 gene leads to false-negative RDT results for P. falciparum.,We have evaluated the extent of pfhrp2 and pfhrp3 gene deletions in a convenience sample of 198 isolates from six sites in three states across the Brazilian Amazon Basin (Acre, Rondonia and Para) and 25 isolates from two sites in Bolivia collected at different times between 2010 and 2012.,Pfhrp2 and pfhrp3 gene and their flanking genes on chromosomes 7 and 13, respectively, were amplified from 198 blood specimens collected in Brazil.,In Brazil, the isolates collected in Acre state, located in the western part of the Brazilian Amazon, had the highest percentage of deletions for pfhrp2 25 (31.2%) of 79, while among those collected in Rondonia, the prevalence of pfhrp2 gene deletion was only 3.3% (2 out of 60 patients).,In isolates from Para state, all parasites were pfhrp2-positive.,In contrast, we detected high proportions of isolates from all 3 states that were pfhrp3-negative ranging from 18.3% (11 out of 60 samples) to 50.9% (30 out of 59 samples).,In Bolivia, only one of 25 samples (4%) tested had deleted pfhrp2 gene, while 68% (17 out of 25 samples) were pfhrp3-negative.,Among the isolates tested, P. falciparum pfhrp2 gene deletions were present mainly in those from Acre State in the Brazilian Amazon.,These results indicate it is important to reconsider the use of PfHRP2-based RDTs in the western region of the Brazilian Amazon and to implement appropriate surveillance systems to monitor pfhrp2 gene deletions in this and other parts of the Amazon region.

Detection of histidine-rich protein 2 (HRP2) from the malaria parasite Plasmodium falciparum provides evidence for active or recent infection, and is utilized for both diagnostic and surveillance purposes, but current laboratory immunoassays for HRP2 are hindered by low sensitivities and high costs.,Here we present a new HRP2 immunoassay based on antigen capture through a bead-based system capable of detecting HRP2 at sub-picogram levels.,The assay is highly specific and cost-effective, allowing fast processing and screening of large numbers of samples.,We utilized the assay to assess results of HRP2-based rapid diagnostic tests (RDTs) in different P. falciparum transmission settings, generating estimates for true performance in the field.,Through this method of external validation, HRP2 RDTs were found to perform well in the high-endemic areas of Mozambique and Angola with 86.4% and 73.9% of persons with HRP2 in their blood testing positive by RDTs, respectively, and false-positive rates of 4.3% and 0.5%.,However, in the low-endemic setting of Haiti, only 14.5% of persons found to be HRP2 positive by the bead assay were RDT positive.,Additionally, 62.5% of Haitians showing a positive RDT test had no detectable HRP2 by the bead assay, likely indicating that these were false positive tests.,In addition to RDT validation, HRP2 biomass was assessed for the populations in these different settings, and may provide an additional metric by which to estimate P. falciparum transmission intensity and measure the impact of interventions.

The Tanzania National Voucher Scheme (TNVS) was a public private partnership managed by the Ministry of Health that provided pregnant women and infants with highly subsidized (long-lasting) insecticide-treated nets between 2004 and 2014.,It was implemented in the context of the National Insecticide Treated Nets (NATNETS) Programme and was the main keep up strategy for vulnerable populations.,The programme design was adjusted considerably over time to incorporate new evidence, shifting public health policies, and changing donor priorities.,Three TNVS models can be distinguished: (1) the fixed discount; (2) the fixed top-up; (3) the hybrid voucher model.,The changes improved equity and effectiveness, but also had a profound effect on how the programme was managed and implemented.,The TNVS reached the majority of beneficiaries with vouchers, and significantly increased household ownership and use of LLINs.,While two mass distribution campaigns implemented between 2009 and 2011 achieved universal coverage and equity, the TNVS ensured continuous protection of the vulnerable populations before, during and after the campaigns.,The TNVS stimulated and maintained a large national retail network which managed the LLIN supply chain.,The effectiveness of the TNVS was a function of several interdependent factors, including the supply chain of vouchers through the public health system; the supply chain of nets in the commercial sector; the demand for nets from voucher recipients; management and risk mitigation measures; and the influence of global and donor objectives.,The TNVS was a highly innovative and globally influential programme, which stimulated the thinking around effectively and equitably distributing ITNs, and contributed directly to the evolution of global policy.,It was a fundamental component of the NATNETS programme which protected a malaria-vulnerable population for over a decade.

Indoor residual spraying (IRS) combined with insecticide treated nets (ITN) has been implemented together in several sub-Saharan countries with inconclusive evidence that the combined intervention provides added benefit.,The impact on malaria transmission was evaluated in a cluster randomised trial comparing two rounds of IRS with bendiocarb plus universal coverage ITNs, with ITNs alone in northern Tanzania.,From April 2011 to December 2012, eight houses in 20 clusters per study arm were sampled monthly for one night with CDC light trap collections.,Anopheles gambiae s.l. were identified to species using real time PCR Taq Man and tested for the presence of Plasmodium falciparum circumsporozoite protein.,ITN and IRS coverage was estimated from household surveys.,IRS coverage was more than 85% in two rounds of spraying in January and April 2012.,Household coverage with at least one ITN per house was 94.7% after the universal coverage net campaign in the baseline year and the proportion of household with all sleeping places covered by LLIN was 50.1% decreasing to 39.1% by the end of the intervention year.,An.gambiae s.s. comprised 80% and An.arabiensis 18.3% of the anopheline collection in the baseline year.,Mean An.gambiae s.l. density in the ITN+IRS arm was reduced by 84% (95%CI: 56%-94%, p = 0.001) relative to the ITN arm.,In the stratum of clusters categorised as high anopheline density at baseline EIR was lower in the ITN+IRS arm compared to the ITN arm (0.5 versus 5.4 per house per month, Incidence Rate Ratio: 0.10, 95%CI: 0.01-0.66, p-value for interaction <0.001).,This trial provides conclusive evidence that combining carbamate IRS and ITNs produces major reduction in Anopheles density and entomological inoculation rate compared to ITN alone in an area of moderate coverage of LLIN and high pyrethroid resistance in An.gambiae s.s.

The last decade has seen a dramatic increase in international and domestic funding for malaria control, coupled with important declines in malaria incidence and mortality in some regions of the world.,As the ongoing climate of financial uncertainty places strains on investment in global health, there is an increasing need to audit the origin, recipients and geographical distribution of funding for malaria control relative to populations at risk of the disease.,A comprehensive review of malaria control funding from international donors, bilateral sources and national governments was undertaken to reconstruct total funding by country for each year 2006 to 2010.,Regions at risk from Plasmodium falciparum and/or Plasmodium vivax transmission were identified using global risk maps for 2010 and funding was assessed relative to populations at risk.,Those nations with unequal funding relative to a regional average were identified and potential explanations highlighted, such as differences in national policies, government inaction or donor neglect.,US$8.9 billion was disbursed for malaria control and elimination programmes over the study period.,Africa had the largest levels of funding per capita-at-risk, with most nations supported primarily by international aid.,Countries of the Americas, in contrast, were supported typically through national government funding.,Disbursements and government funding in Asia were far lower with a large variation in funding patterns.,Nations with relatively high and low levels of funding are discussed.,Global funding for malaria control is substantially less than required.,Inequity in funding is pronounced in some regions particularly when considering the distinct goals of malaria control and malaria elimination.,Efforts to sustain and increase international investment in malaria control should be informed by evidence-based assessment of funding equity.

Since 2005, malaria control scale-up has progressed in many African countries.,Controlled studies of insecticide-treated mosquito nets (ITNs), indoor residual spraying (IRS), intermittent preventive treatment during pregnancy (IPTp) and malaria case management suggested that when incorporated into national programmes a dramatic health impact, likely more than a 20% decrease in all-cause childhood mortality, was possible.,To assess the extent to which national malaria programmes are achieving impact the authors reviewed African country programme data available through 2009.,National survey data, published literature, and organization or country reports produced during 2000-2009 were reviewed to assess available malaria financing, intervention delivery, household or target population coverage, and reported health benefits including infection, illness, severe anaemia, and death.,By the end of 2009, reports were available for ITN household ownership (n = 34) and IPTp use (n = 27) in malaria-endemic countries in Africa, with at least two estimates (pre-2005 and post-2005 intervals).,Information linking IRS and case management coverage to impact were more limited.,There was generally at least a three-fold increase in household ITN ownership across these countries between pre-2005 (median of 2.4% of households with at least one ITN) and post-2005 (median of 32.5% of households with at least one ITN).,Ten countries had temporal data to assess programme impact, and all reported progress on at least one impact indicator (typically on mortality); in under-five year mortality rates most observed a decline of more than 20%.,The causal relationship between malaria programme scale-up and reduced child illness and mortality rates is supported by biologic plausibility including mortality declines consistent with experience from intervention efficacy trials, consistency of findings across multiple countries and different epidemiologic settings, and temporal congruity where morbidity and mortality declines have been documented in the 18 to 36 months following intervention scale-up.,Several factors potentially have contributed to recent health improvement in African countries, but there is substantial evidence that achieving high malaria control intervention coverage, especially with ITNs and targeted IRS, has been the leading contributor to reduced child mortality.,The documented impact provides the evidence required to support a global commitment to the expansion and long-term investment in malaria control to sustain and increase the health impact that malaria control is producing in Africa.

Mosquito‐borne diseases cause a major burden of disease worldwide.,The vital rates of these ectothermic vectors and parasites respond strongly and nonlinearly to temperature and therefore to climate change.,Here, we review how trait‐based approaches can synthesise and mechanistically predict the temperature dependence of transmission across vectors, pathogens, and environments.,We present 11 pathogens transmitted by 15 different mosquito species - including globally important diseases like malaria, dengue, and Zika - synthesised from previously published studies.,Transmission varied strongly and unimodally with temperature, peaking at 23-29ºC and declining to zero below 9-23ºC and above 32-38ºC.,Different traits restricted transmission at low versus high temperatures, and temperature effects on transmission varied by both mosquito and parasite species.,Temperate pathogens exhibit broader thermal ranges and cooler thermal minima and optima than tropical pathogens.,Among tropical pathogens, malaria and Ross River virus had lower thermal optima (25-26ºC) while dengue and Zika viruses had the highest (29ºC) thermal optima.,We expect warming to increase transmission below thermal optima but decrease transmission above optima.,Key directions for future work include linking mechanistic models to field transmission, combining temperature effects with control measures, incorporating trait variation and temperature variation, and investigating climate adaptation and migration.

There has been considerable debate on the existence of trends in climate in the highlands of East Africa and hypotheses about their potential effect on the trends in malaria in the region.,We apply a new robust trend test to mean temperature time series data from three editions of the University of East Anglia's Climatic Research Unit database (CRU TS) for several relevant locations.,We find significant trends in the data extracted from newer editions of the database but not in the older version for periods ending in 1996.,The trends in the newer data are even more significant when post-1996 data are added to the samples.,We also test for trends in the data from the Kericho meteorological station prepared by Omumbo et al.,We find no significant trend in the 1979-1995 period but a highly significant trend in the full 1979-2009 sample.,However, although the malaria cases observed at Kericho, Kenya rose during a period of resurgent epidemics (1994-2002) they have since returned to a low level.,A large assembly of parasite rate surveys from the region, stratified by altitude, show that this decrease in malaria prevalence is not limited to Kericho.

Ayeyarwady Region in Myanmar has made significant progress towards malaria elimination, with cases decreasing from 12,312 in 2015 to 122 in 2019.,As transmission declines, malaria becomes increasingly focalized both in geographic hotspots and among population groups sharing certain risk factors.,Developing a thorough profile of high-risk activities associated with malaria infections is critical to ensure intervention approaches are evidence-based.,A test-negative study was conducted from September 2017 to May 2018 in Ngaputaw, Pathein and Thabaung townships in Ayeyarwady Region.,Patients that presented to selected public facilities or community health volunteers with fever answered survey questions on demographic and behavioural risk factors, including exposure to malaria interventions, and were assigned to case and control groups based on the result of a malaria rapid diagnostic test.,A random-effects logistic regression model adjusted for clustering at the facility level, as well as any variables along the causal pathway described by a directed acyclic graph, was used to determine odds ratios and association with malaria infections.,A total of 119 cases and 1744 controls were recruited from 41 public facilities, with a mean age of 31.3 and 63.7% male.,Higher risk groups were identified as males (aOR 1.8, 95% CI 1.2-2.9) and those with a worksite located within the forest (aOR 2.8, 95% CI 1.4-5.3), specifically working in the logging (aOR 2.7, 95% CI 1.5-4.6) and rubber plantation (aOR 3.0, 95% CI 1.4-6.8) industries.,Additionally, links between forest travel and malaria were observed, with risk factors identified to be sleeping in the forest within the past month (aOR 2.6, 95% CI 1.1-6.3), and extended forest travel with durations from 3 to 14 days (aOR 8.6, 95% CI 3.5-21.4) or longer periods (aOR 8.4, 95% CI 3.2-21.6).,Malaria transmission is highly focalized in Ayeyarwady, and results illustrate the need to target interventions to the most at-risk populations of working males and forest goers.,It will become increasingly necessary to ensure full intervention coverage of at-risk populations active in forested areas as Myanmar moves closer to malaria elimination goals.,The online version contains supplementary material available at 10.1186/s12936-022-04088-8.

Understanding malaria along the international border of two countries is important for malaria control and elimination; however, it is difficult to investigate a quantitative relationship between two countries’ border areas due to a shortage of malaria surveillance data.,A linear regression analysis was conducted to investigate the logarithmic annual parasite incidence (API), numbers of imported cases and local infections in 19 Chinese border counties, with logarithmic API and parasitic prevalence in Myanmar’s five special regions.,API in 19 Chinese counties was stronger correlated with parasite prevalence than with API in five special regions of Myanmar, correlation coefficient (R) 0.8322 (95 % CI 0.0636-0.9084) versus 0.9914 (95 % CI 0.9204-0.9914).,Numbers of imported malaria cases and local malaria infections in 19 Chinese counties were also closer correlated with parasite prevalence than with API in five special regions of Myanmar.,There is a strong correlation of malaria between China’s side and Myanmar’s side along the international border.,Parasite prevalence is a better indicator of the true malaria situation in a setting without sound surveillance and reporting system.,China should reconsider its definition of imported malaria which neglects imported malaria by mosquitoes and asymptomatic parasite carriers.,The online version of this article (doi:10.1186/s12936-016-1413-4) contains supplementary material, which is available to authorized users.