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In China, the prevalence of malaria has reduced dramatically due to the elimination programme.,The continued success of the programme will depend upon the accurate diagnosis of the disease in the laboratory.,The basic requirements for this are a reliable malaria diagnosis laboratory network and quality management system to support case verification and source tracking.,The baseline information of provincial malaria laboratories in the China malaria diagnosis reference laboratory network was collected and analysed, and a quality-assurance activity was carried out to assess their accuracies in malaria diagnosis by microscopy using WHO standards and PCR.,By the end of 2013, nineteen of 24 provincial laboratories have been included in the network.,In the study, a total of 168 staff were registered and there was no bias in their age, gender, education level, and position.,Generally Plasmodium species were identified with great accuracy by microscopy and PCR.,However, Plasmodium ovale was likely to be misdiagnosed as Plasmodium vivax by microscopy.,China has established a laboratory network for primary malaria diagnosis which will cover a larger area.,Currently, Plasmodium species can be identified fairly accurately by microscopy and PCR.,However, laboratory staff need additional trainings on accurate identification of P. ovale microscopically and good performance of PCR operations.

Recent progress in malaria control has caused renewed interest in mass drug administration (MDA) as a potential elimination strategy but the evidence base is limited.,China has extensive experience with MDA, but it is not well documented.,An ecological study was conducted to describe the use of MDA for the control and elimination of Plasmodium vivax in Jiangsu Province and explore the association between MDA and malaria incidence.,Two periods were focused on: 1973 to 1983 when malaria burden was high and MDA administered to highly endemic counties province-wide, and 2000 to 2009, when malaria burden was low and a focal approach was used in two counties.,All available data about the strategies implemented, MDA coverage, co-interventions, incidence, and adverse events were collected and described.,Joinpoint analysis was used to describe trends in incidence and the relationship between MDA coverage and incidence was explored in negative binomial regression models.,From 1973 to 1983, MDA with pyrimethamine and primaquine was used on a large scale, with up to 30 million people in target counties covered in a peak year (50% of the total population).,Joinpoint analyses identified declines in annual incidence, -56.7% (95% CI -75.5 to -23.7%) from 1973-1976 and -12.4% (95% CI -24.7 to 2.0%) from 1976-1983.,Population average negative binomial models identified a relationship between higher total population MDA coverage and lower monthly incidence from 1973-1976, IRR 0.98 (95% CI 0.97 to 1.00), while co-interventions, rainfall and GDP were not associated.,From 2000-2009, incidence in two counties declined (annual change -43.7 to -14.0%) during a time when focal MDA using chloroquine and primaquine was targeted to villages and/or individuals residing near passively detected index cases (median 0.04% of total population).,Although safety data were not collected systematically, there were rare reports of serious but non-fatal events.,In Jiangsu Province, China, large-scale MDA was implemented and associated with declines in high P. vivax malaria transmission; a more recent focal approach may have contributed to interruption of transmission.,MDA should be considered a potential key strategy for malaria control and elimination.

The zoonotic parasite Taenia solium is endemic in Angónia district, Tete province, Mozambique, though the burden of the disease complex is unknown.,As part of two cross-sectional studies on human and porcine cysticercosis in the area, unique epidemiological and cost data were collected in Angónia district, Mozambique in 2007.,These data provided the basis for the assessment of the societal cost of T. solium in the district, which estimates the impact of the disease on human and pig populations and includes both health and economic approaches in the analysis.,Approximately 0.7% (95% Uncertainty Interval (UI), 0.4-0.9) and 0.4% (95% UI, 0.2-0.6) of the total population in the district was estimated to suffer from neurocysticercosis (NCC)-associated epilepsy and headache.,The estimated average number of disability-adjusted life years (DALYs) due to NCC-associated epilepsy and headache was 6 (95% UI, 4-8) per thousand persons per year.,The total annual costs due to T. solium cysticercosis were estimated at 90,000 USD (95% UI, 39,483-201,463) of which 72% (95% UI, 45-91) were costs linked to human cysticercosis and 28% (95% UI, 9.5-55) to pig production losses.,The annual economic burden per NCC-associated epilepsy case in the district amounted to 33 USD (95% UI, 10-76).,In this highly endemic area of Mozambique a large number of individuals suffer from symptoms associated with NCC.,Healthy years of life are lost and people are left living with disabilities.,Infected pork poses a serious risk to the community and affects the economy of smallholder farmers.,Cost for treatment and hospitalization of patients with NCC-associated epilepsy, and lack of productivity and inability of suffering patients to work, further hinder socioeconomic development.,Feasible solutions framed within a country specific algorithm and stepwise approaches are needed to control the parasite in the country.

The pork tapeworm, Taenia solium, and associated human infections, taeniasis, cysticercosis and neurocysticercosis, are serious public health problems, especially in developing countries.,The World Health Organization (WHO) has set goals for having a validated strategy for control and elimination of T. solium taeniasis/cysticercosis by 2015 and interventions scaled-up in selected countries by 2020.,Timely achievement of these internationally-endorsed targets requires that the relative benefits and effectiveness of potential interventions be explored rigorously within a quantitative framework.,A deterministic, compartmental transmission model (EPICYST) was developed to capture the dynamics of the taeniasis/cysticercosis disease system in the human and pig hosts.,Cysticercosis prevalence in humans, an outcome of high epidemiological and clinical importance, was explicitly modelled.,A next generation matrix approach was used to derive an expression for the basic reproduction number, R 0.,A full sensitivity analysis was performed using a methodology based on Latin-hypercube sampling partial rank correlation coefficient index.,EPICYST outputs indicate that chemotherapeutic intervention targeted at humans or pigs would be highly effective at reducing taeniasis and cysticercosis prevalence when applied singly, with annual chemotherapy of humans and pigs resulting, respectively, in 94 and 74% of human cysticercosis cases averted.,Improved sanitation, meat inspection and animal husbandry are less effective but are still able to reduce prevalence singly or in combination.,The value of R 0 for taeniasis was estimated at 1.4 (95% Credible Interval: 0.5-3.6).,Human- and pig-targeted drug-focussed interventions appear to be the most efficacious approach from the options currently available.,The model presented is a forward step towards developing an informed control and elimination strategy for cysticercosis.,Together with its validation against field data, EPICYST will be a valuable tool to help reach the WHO goals and to conduct economic evaluations of interventions in varying epidemiological settings.,The online version of this article (doi:10.1186/s13071-017-1988-9) contains supplementary material, which is available to authorized users.

Schistosomiasis is a parasitic disease affecting over 250 million people in the tropics.,In non-endemic regions, imported Schistosoma infections are commonly diagnosed by serology, but based on antibody detection an active infection cannot be distinguished from a cured infection and it may take more than 8 weeks after exposure before seroconversion occurs.,In endemic populations, excellent results have been described in diagnosing low-grade active Schistosoma infections by the detection of the adult worm-derived circulating anodic antigen (CAA) utilising robust lateral flow (LF) assays combined with up-converting phosphor (UCP) reporter technology.,The purpose of this study is to explore the diagnostic value of the UCP-LF CAA assay in a non-endemic setting.,CAA concentrations were determined in 111 serum samples originating from 81 serology-positive individuals.,In nine individuals, serum could be collected before travel and an additional five provided samples before and after seroconversion occurred.,Based on detectable CAA levels, an active infection was seen in 56/81 (69%) of the exposed individuals, while the 10 controls and the 9 sera collected before travel were tested negative for CAA.,Positive CAA levels were observed starting 4 weeks after exposure and in four cases CAA was detected even before Schistosoma-specific antibodies became positive.,Higher serum CAA levels were seen in migrants than in travellers and CAA concentrations dropped sharply when testing follow-up samples after treatment.,This explorative study indicates the UCP-LF CAA serum assay to be a highly accurate test for detecting active low-grade Schistosoma infections in a non-endemic routine diagnostic setting.

This study evaluated parasitological and molecular techniques for the diagnosis and assessment of cure of schistosomiasis mansoni.,A population-based study was performed in 201 inhabitants from a low transmission locality named Pedra Preta, municipality of Montes Claros, state of Minas Gerais, Brazil.,Four stool samples were analysed using two techniques, the Kato-Katz® (KK) technique (18 slides) and the TF-Test®, to establish the infection rate.,The positivity rate of 18 KK slides of four stool samples was 28.9% (58/201) and the combined parasitological techniques (KK+TF-Test®) produced a 35.8% positivity rate (72/201).,Furthermore, a polymerase chain reaction (PCR)-ELISA assay produced a positivity rate of 23.4% (47/201) using the first sample.,All 72 patients with positive parasitological exams were treated with a single dose of Praziquantel® and these patients were followed-up 30, 90 and 180 days after treatment to establish the cure rate.,Cure rates obtained by the analysis of 12 KK slides were 100%, 100% and 98.4% at 30, 90 and 180 days after treatment, respectively.,PCR-ELISA revealed cure rates of 98.5%, 95.5% and 96.5%, respectively.,The diagnostic and assessment of cure for schistosomiasis may require an increased number of KK slides or a test with higher sensitivity, such as PCR-ELISA, in situations of very low parasite load, such as after therapeutic interventions.

Transmission reduction is a key component of global efforts to control and eliminate malaria; yet, it is unclear how the density of transmission stages (gametocytes) influences infection (proportion of mosquitoes infected).,Human to mosquito transmission was assessed using 171 direct mosquito feeding assays conducted in Burkina Faso and Kenya.,Plasmodium falciparum infects Anopheles gambiae efficiently at low densities (4% mosquitoes at 1/µl blood), although substantially more (>200/µl) are required to increase infection further.,In a site in Burkina Faso, children harbour more gametocytes than adults though the non-linear relationship between gametocyte density and mosquito infection means that (per person) they only contribute slightly more to transmission.,This method can be used to determine the reservoir of infection in different endemic settings.,Interventions reducing gametocyte density need to be highly effective in order to halt human-mosquito transmission, although their use can be optimised by targeting those contributing the most to transmission.,DOI:http://dx.doi.org/10.7554/eLife.00626.001,Malaria is one of the world’s most deadly infectious diseases.,The most severe form is caused by the parasite Plasmodium falciparum, which can reside within red blood cells and thus evade the human immune system.,Plasmodium is transmitted between humans by mosquitoes.,When a mosquito takes a blood meal from an individual infected with the parasite, the insect ingests Plasmodium gametocytes (i.e., eggs and sperm), and these go on to reproduce in the gut of the mosquito.,These parasites then move to the mosquito’s salivary glands, to be injected into the next person whom the mosquito bites.,Although malaria is both preventable and curable, the mortality rates in many African countries remain high, especially among children.,Reducing the transmission of malaria to mosquitoes is one of the primary goals in the global effort to control and eliminate the disease.,While a range of drugs and vaccines that specifically try to reduce transmission are in development, non-medical interventions such as mosquito nets and insecticide spraying can quickly and effectively reduce infection rates.,Here, Churcher et al. examine the dynamics of human to mosquito transmission of P. falciparum, and report that the ease with which mosquitoes become infected is not directly proportional to the density of parasite gametocytes in human blood.,They found that the transmission occurs readily at very low gametocyte densities.,Moreover, the transmission rate remains relatively stable as the density increases, before increasing significantly when the density reaches around 200 cells per microlitre.,Churcher et al. also challenge the assumption that children are mostly responsible for transmitting the malaria parasite by suggesting that, in certain locations, there is a more significant role for adults than previously assumed.,By identifying the groups that contribute most to transmission, and targeting resources to reduce gametocyte density in those individuals, it could be possible to greatly reduce the number of infected mosquitoes and, therefore, the number of infected humans.,DOI:http://dx.doi.org/10.7554/eLife.00626.002

The coexistence of multiple independently circulating strains in pathogen populations that undergo sexual recombination is a central question of epidemiology with profound implications for control.,An agent-based model is developed that extends earlier ‘strain theory’ by addressing the var gene family of Plasmodium falciparum.,The model explicitly considers the extensive diversity of multi-copy genes that undergo antigenic variation via sequential, mutually exclusive expression.,It tracks the dynamics of all unique var repertoires in a population of hosts, and shows that even under high levels of sexual recombination, strain competition mediated through cross-immunity structures the parasite population into a subset of coexisting dominant repertoires of var genes whose degree of antigenic overlap depends on transmission intensity.,Empirical comparison of patterns of genetic variation at antigenic and neutral sites supports this role for immune selection in structuring parasite diversity.,DOI:http://dx.doi.org/10.7554/eLife.00093.001,Malaria is an infectious disease that is estimated to kill more than half a million people every year, mostly young children in Africa.,It is spread by mosquitos that are infected with Plasmodium parasites that attack red blood cells in the human body.,Plasmodium falciparum, the species that is responsible for most of these deaths, causes malaria by entering red blood cells and releasing antigens that travel to the surface of the cells, where they change the adhesion properties.,This causes the infected red blood cells to accumulate in small blood vessels, surface capillaries or the brain, which can have severe consequences for the person infected.,P. falciparum is particularly dangerous because of its ability to vary the antigens displayed on the cell surface: this process, known as antigenic variation, helps to maintain infections for extended periods of time by allowing the antigens to stay one step ahead of the immune system (a process known as immune escape).,The origins of antigenic variation lie in the fact that each P. falciparum genome has a repertoire of between 50 and 60 var genes that code for the variability of a major antigen that is responsible for immune escape in malaria.,Molecular sequencing has shown that local parasite populations contain thousands of different types of var genes: hence, meiotic recombination in the mosquito can create a vast number of combinations of var repertoires.,Artzy-Randrup et al. have developed a computational model of this highly diverse and complex system to address the following question: is a local pathogen population composed of largely random and ephemeral repertoires of these genes, or is it structured into independently circulating strains?,Their model goes beyond previous models by including interactions within the local host population that arise as a result of indirect competition between different strains of the pathogen for available hosts: this competition is influenced by the history of infection and, therefore, by the patterns of immunity within the host population.,Previous models included within-host processes but not these higher, local population-level interactions.,The model simulates the dynamics of all the unique combinations of var genes in a population of hosts, and shows that even with high rates of reproduction, the parasite population self-organizes into a limited number of coexisting strains: the distinct var repertoires of these strains only weakly overlap, suggesting that the immune response of the host population has been partitioned into distinct niches.,By investigating genetic variation at both antigenic sites and regions of the genome that do not code for antigens, Artzy-Randrup et al. suggest that immune selection-the selection imposed on var repertoires by the build up of specific immunity at the population level-plays a central role in structuring parasite diversity.,The new model should lead to a better understanding of the epidemiology of Plasmodium and other pathogens that work in similar ways, including Trypanosoma brucei (sleeping sickness), Borellia burgdorferi (Lyme disease) and Giardia lamblia (gastroenteritis), and help with global efforts to eliminate malaria and other diseases.,DOI:http://dx.doi.org/10.7554/eLife.00093.002

Signal recognition particle (SRP) is a ubiquitous ribonucleoprotein complex that targets proteins to endoplasmic reticulum (ER) in eukaryotes.,Here we report that Plasmodium falciparum SRP is composed of six polypeptides; SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72 and a 303nt long SRP RNA.,We generated four transgenic parasite lines expressing SRP-GFP chimeric proteins and co-localization studies showed the nucleo-cytoplasmic localization for these proteins.,The evaluation of the effect of known SRP and nuclear import/export inhibitors on P. falciparum revealed that ivermectin, an inhibitor of importin α/β mediated nuclear import inhibited the nuclear import of PfSRP polypeptides at submicromolar concentration, thereby killing the parasites.,These findings provide insights into dynamic structure of P. falciparum SRP and also raise the possibility that ivermectin could be used in combination with other antimalarial agents to control the disease.

The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite.,A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success.,We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections.,A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis.,The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described.,Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals.,We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota.,Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status.,This striking relationship highlights the role of natural gut environment in parasite transmission.,Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.

Because of the low sensitivity of conventional rapid diagnostic tests (RDTs) for malaria infections, the actual prevalence of the diseases, especially those caused by non-Plasmodium falciparum (non-Pf) species, in asymptomatic populations remain less defined in countries lacking in well-equipped facilities for accurate diagnoses.,Our direct blood dry LAMP system (CZC-LAMP) was applied to the diagnosis of malaria as simple, rapid and highly sensitive method as an alternative for conventional RDTs in malaria endemic areas where laboratory resources are limited.,LAMP primer sets for mitochondria DNAs of Plasmodium falciparum (Pf) and human-infective species other than Pf (non-Pf; P. vivax, P. ovale, P. malariae) were designed and tested by using human blood DNA samples from 74 residents from a malaria endemic area in eastern Zambia.,These malaria dry-LAMPs were optimized for field or point-of-care operations, and evaluated in the field at a malaria endemic area in Zambia with 96 human blood samples.,To determine the sensitivities and specificities, results obtained by the on-site LAMP diagnosis were compared with those by the nested PCR and nucleotide sequencing of its product.,The dry LAMPs showed the sensitivities of 89.7% for Pf and 85.7% for non-Pf, and the specificities of 97.2% for Pf and 100% for non-Pf, with purified blood DNA samples.,The direct blood LAMP diagnostic methods, in which 1 μl of anticoagulated blood were used as the template, showed the sensitivities of 98.1% for Pf, 92.1% for non-Pf, and the specificities of 98.1% for Pf, 100% for non-Pf.,The prevalences of P. falciparum, P. malariae and P. ovale in the surveyed area were 52.4, 25.3 and 10.6%, respectively, indicating high prevalence of asymptomatic carriers in endemic areas in Zambia.,We have developed new field-applicable malaria diagnostic tests.,The malaria CZC-LAMPs showed high sensitivity and specificity to both P. falciparum and non-P. falciparum.,These malaria CZC-LAMPs provide new means for rapid, sensitive and reliable point-of-care diagnosis for low-density malaria infections, and are expected to help update current knowledge of malaria epidemiology, and can contribute to the elimination of malaria from endemic areas.,The online version of this article (doi:10.1186/s13071-016-1949-8) contains supplementary material, which is available to authorized users.

Isothermal nucleic acid amplification assays such as the loop mediated isothermal amplification (LAMP), are well suited for field use as they do not require thermal cyclers to amplify the DNA.,To further facilitate the use of LAMP assays in remote settings, simpler sample preparation methods and lyophilized reagents are required.,The performance of a commercial malaria LAMP assay (Illumigene Malaria LAMP) was evaluated using two sample preparation workflows (simple filtration prep (SFP)) and gravity-driven filtration prep (GFP)) and pre-dispensed lyophilized reagents.,Laboratory and clinical samples were tested in a field laboratory in Senegal and the results independently confirmed in a reference laboratory in the U.S.A.,The Illumigene Malaria LAMP assay was easily implemented in the clinical laboratory and gave similar results to a real-time PCR reference test with limits of detection of ≤2.0 parasites/μl depending on the sample preparation method used.,This assay reliably detected Plasmodium sp. parasites in a simple low-tech format, providing a much needed alternative to the more complex molecular tests for malaria diagnosis.

Leishmaniasis is an important health problem in several countries in the Americas and cases notification is limited and underreported.,In 2008, the Pan American Health Organization (PAHO/WHO) met with endemic countries to discuss the status and need of improvement of systems region-wide.,The objective is to describe the temporal and spatial distribution of cutaneous leishmaniasis (CL) cases reported to PAHO/WHO by the endemic countries between 2001 and 2011 in the Americas.,Cases reported in the period of 2001-2011 from 14/18 CL endemic countries were included in this study by using two spreadsheet to collect the data.,Two indicators were analyzed: CL cases and incidence rate.,The local regression method was used to analyze case trends and incidence rates for all the studied period, and for 2011 the spatial distribution of each indicator was analyzed by quartile and stratified into four groups.,From 2001-2011, 636,683 CL cases were reported by 14 countries and with an increase of 30% of the reported cases.,The average incidence rate in the Americas was 15.89/100,000 inhabitants.,In 2011, 15 countries reported cases in 180 from a total of 292 units of first subnational level.,The global incidence rate for all countries was 17.42 cases per 100,000 inhabitants; while in 180 administrative units at the first subnational level, the average incidence rate was 57.52/100,000 inhabitants.,Nicaragua and Panama had the highest incidence but more cases occurred in Brazil and Colombia.,Spatial distribution was heterogeneous for each indicator, and when analyzed in different administrative level.,The results showed different distribution patterns, illustrating the limitation of the use of individual indicators and the need to classify higher-risk areas in order to prioritize the actions.,This study shows the epidemiological patterns using secondary data and the importance of using multiple indicators to define and characterize smaller territorial units for surveillance and control of leishmaniasis.

As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 countries and three territories (see ‘Leishmaniasis Country Profiles Text S1, S2, S3, S4, S5, S6, S7, S8, S9, S10, S11, S12, S13, S14, S15, S16, S17, S18, S19, S20, S21, S22, S23, S24, S25, S26, S27, S28, S29, S30, S31, S32, S33, S34, S35, S36, S37, S38, S39, S40, S41, S42, S43, S44, S45, S46, S47, S48, S49, S50, S51, S52, S53, S54, S55, S56, S57, S58, S59, S60, S61, S62, S63, S64, S65, S66, S67, S68, S69, S70, S71, S72, S73, S74, S75, S76, S77, S78, S79, S80, S81, S82, S83, S84, S85, S86, S87, S88, S89, S90, S91, S92, S93, S94, S95, S96, S97, S98, S99, S100, S101’).,Additional information was collated during meetings conducted at WHO regional level between 2007 and 2011.,Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers.,Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts.,Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year.,More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil.,Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia.,The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica and Peru, together account for 70 to 75% of global estimated CL incidence.,Mortality data were extremely sparse and generally represent hospital-based deaths only.,Using an overall case-fatality rate of 10%, we reach a tentative estimate of 20,000 to 40,000 leishmaniasis deaths per year.,Although the information is very poor in a number of countries, this is the first in-depth exercise to better estimate the real impact of leishmaniasis.,These data should help to define control strategies and reinforce leishmaniasis advocacy.

Pigs are kept by farmers as a source of livelihood and food.,Unfortunately, helminthiasis and other internal parasites are major setbacks to profitable pig production in Africa.,There is a lack of information on the prevalence and intensity of gastrointestinal helminths and parasites plaguing resource-poor pig farmers in the Free State.,Knowledge of these endemic parasites can be used as baseline data to help design future intervention plans.,The aim of this study was to identify and quantify the types of gastrointestinal helminths and parasites prevalent in smallholder pigs reared in the central Free State Province.,Faecal samples were randomly collected from 77 pigs and parasitologically analysed.,Quantification was done using the McMaster counting technique.,Farming system, age, gender and health status were the risk factors considered.,The study was conducted between January and March 2016.,Overall, results showed that 61 samples (79.2%) tested positive for one or more gastrointestinal parasites, which were observed as single or mixed infections.,Amongst the positive samples, 44.5% were infected with Ascaris suum, 50.6% with Trichuris suis, 26.0% and 72.7% were infected with Oesophagostomum dentatum and coccidia, respectively.,There were significant differences (p < 0.05) between the rate of infection in the intensive and semi-intensive systems and between the dewormed and non-dewormed pigs.,Piglets and female pigs recorded a higher prevalence in their categories.,Pigs excreted mostly low (eggs per gram [EPG] ≤ 100) to moderate (EPG > 100 < 500) levels of helminth eggs.,It is concluded that different species of gastrointestinal parasites are present in most pigs reared by smallholder farmers in this study area.,Keywords: gastrointestinal helminths and parasites; smallholder pig farmers; pigs; prevalence; Central Free State Province.

Cryptosporidium spp. are common intestinal protozoa of humans and animals.,There have been few studies conducted on the molecular characterizations of pig-derived Cryptosporidium isolates worldwide, especially in China.,Thus, the aim of the present study was to understand the prevalence, distribution and genotypes of Cryptosporidium in pigs in Heilongjiang Province, China.,A total of 568 fecal samples from pre-weaned and post-weaned piglets were collected from eight pig farms from four areas of Heilongjiang Province.,The average infection rate of Cryptosporidium was 1.6% (9/568) by microscopy. 113 samples were subjected to PCR amplification of the small subunit (SSU) rRNA gene of Cryptosporidium, with 55.8% (63/113) being positive for Cryptosporidium.,Cryptosporidium suis (n = 31) and C. scrofarumn (n = 32) were identified by DNA sequencing of the SSU rRNA gene.,Three types of C. scrofarumn were found at the SSU rRNA locus, with one novel type being detected.,Using species/genotype-specific primers for pig-adapted Cryptosporidium spp., 22 and 23 respectively belonged to C. suis and C. scrofarum mono-infections, with 18 co-infections detected.,The infection peaks for C. suis (60%, 24/40) and C. scrofarum (51.2%, 21/41) were respectively found in the piglets of 5 to 8 weeks and more than 8 weeks.,The detection of C. suis and C. scrofarum in pre-weaned and post-weaned piglets has public health implications, due to the fact that the two species are both zoonotic Cryptosporidium.,The novel C. scrofarum type detected may be endemic to China.

Naturally acquired immunity against clinical malaria is slow to develop, taking years of repeated exposure to parasites to acquire sufficiently broad and potent antibody responses.,Increasing evidence suggests that Plasmodium infection and the resulting immune stimulation contribute to changes in the B cell compartment.,In particular, accumulation of atypical memory B cells (atMBCs) is common in Plasmodium-exposed individuals.,Similarities to B cell subsets present in other acute and chronic disease settings have provided insight into the development and potential function of these cells; however, their contribution to protection against malaria is still poorly understood.,Here, we discuss recent findings that have increased our understanding of atMBCs and outline outstanding questions related to their function and development in the protective immune response to malaria.

BACKGROUND.,Drugs and vaccines that can interrupt the transmission of Plasmodium falciparum will be important for malaria control and elimination.,However, models for early clinical evaluation of candidate transmission-blocking interventions are currently unavailable.,Here, we describe a new model for evaluating malaria transmission from humans to Anopheles mosquitoes using controlled human malaria infection (CHMI).,METHODS.,Seventeen healthy malaria-naive volunteers underwent CHMI by intravenous inoculation of P. falciparum-infected erythrocytes to initiate blood-stage infection.,Seven to eight days after inoculation, participants received piperaquine (480 mg) to attenuate asexual parasite replication while allowing gametocytes to develop and mature.,Primary end points were development of gametocytemia, the transmissibility of gametocytes from humans to mosquitoes, and the safety and tolerability of the CHMI transmission model.,To investigate in vivo gametocytocidal drug activity in this model, participants were either given an experimental antimalarial, artefenomel (500 mg), or a known gametocytocidal drug, primaquine (15 mg), or remained untreated during the period of gametocyte carriage.,RESULTS.,Male and female gametocytes were detected in all participants, and transmission to mosquitoes was achieved from 8 of 11 (73%) participants evaluated.,Compared with results in untreated controls (n = 7), primaquine (15 mg, n = 5) significantly reduced gametocyte burden (P = 0.01), while artefenomel (500 mg, n = 4) had no effect.,Adverse events (AEs) were mostly mild or moderate.,Three AEs were assessed as severe - fatigue, elevated alanine aminotransferase, and elevated aspartate aminotransferase - and were attributed to malaria infection.,Transaminase elevations were transient, asymptomatic, and resolved without intervention.,CONCLUSION.,We report the safe and reproducible induction of P. falciparum gametocytes in healthy malaria-naive volunteers at densities infectious to mosquitoes, thereby demonstrating the potential for evaluating transmission-blocking interventions in this model.,TRIAL REGISTRATION.,ClinicalTrials.gov NCT02431637 and NCT02431650.,FUNDING.,Bill & Melinda Gates Foundation.

India is home to 60% of the total global visceral leishmaniasis (VL) population.,Use of long-term oral (e.g. miltefosine) and parenteral drugs, considered the mainstay for treatment of VL, is now faced with increased resistance, decreased efficacy, low compliance and safety issues.,The authors evaluated the efficacy and safety of an alternate treatment option, i.e. single infusion of preformed amphotericin B (AmB) lipid emulsion (ABLE) in comparison with that of liposomal formulation (LAmB).,In this multicentric, open-label study, 500 patients with VL were randomly assigned in a 3∶1 ratio to receive 15 mg/kg single infusion of either ABLE (N = 376) or LAmB (N = 124).,Initial cure (Day 30/45), clinical improvement (Day 30) and long term definitive cure (Day 180) were assessed.,A total of 326 (86.7%) patients in the ABLE group and 122 (98.4%) patients in the LAmB group completed the study.,Initial cure was achieved by 95.9% of patients in the ABLE group compared to 100% in the LAmB group (p = 0.028; 95% CI: −0.0663, −0.0150).,Clinical improvement was comparable between treatments (ABLE: 98.9% vs.,LAmB: 98.4%).,Definitive cure was achieved in 85.9% with ABLE compared to 98.4% with LAmB.,Infusion-related pyrexia (37.2% vs.,32.3%) and chills (18.4% vs.,18.5%) were comparable between ABLE and LAmB, respectively.,Treatment-related serious adverse events were fewer in ABLE (0.3%) compared to LAmB (1.6%).,Two deaths occurred in the ABLE group, of which one was probably related to the study drug.,Nephrotoxicity and hepatotoxicity was not observed in either group.,ABLE 15 mg/kg single infusion had favorable efficacy and was well tolerated.,Considering the demographic profile of the population in this region, a single dose treatment offers advantages in terms of compliance, cost and applicability.,www.clinicaltrials.govNCT00876824

In 2005, Bangladesh, India, and Nepal joined forces to eliminate Visceral Leishmaniasis (or kala-azar) from the region by 2015.,In Bangladesh the elimination target is set at less than one new case per 10,000 population per year at upazila (sub-district) level.,As the deadline approaches, we review the status of the elimination initiative in this country.,We collected all available disease surveillance data at the Disease Control Unit of the Directorate General of Health Services, Government of Bangladesh from 1994 to 2013.,Additionally, we retrieved data from the Civil Surgeon Office from the Mymensingh district, one of the most heavily affected areas in Bangladesh.,Between 1994 and 2013, 109,266 kala-azar cases causing 329 deaths were reported from 37 endemic districts in Bangladesh.,Only 16 districts reported cases every year.,The Mymensingh district was the most affected with 53,582 (49.04%) cases.,Between 2008 and 2013 only 16 upazilas showed incidence rates above the elimination target in which they ranged from 1.06 to 18.25 per 10,000 people per year.,While clear progress has been made towards eliminating VL, 16 upazilas in Bangladesh had not yet reached the target in 2013, based on official notification data that probably suffered from under-reporting bias.,The elimination initiative urgently needs to establish methods to ascertain and monitor the elimination target.

The World Health Assembly endorsed the WHO Neglected Tropical Disease (NTD) Roadmap in 2013, in which NTDs were suggested as tracers of equity in the assessment of progress towards the Sustainable Development Goals.,Nationwide surveys were undertaken in all 18 states of Sudan to identify the geographical distribution and to estimate the prevalence and intensity of schistosomiasis and other intestinal helminthiases from December 2016 to March 2017.,We used two-stage random sampling.,Each district was subdivided into one to three different ecological zones (EZs) based on proximity to water bodies.,Probability-proportional-to-size sampling was used to select schools from each EZ.,We estimated schistosomiasis and intestinal helminthiasis prevalence by the centrifugation method and Kato-Katz smears.,Multi-level mixed-effect models were used to investigate the relationship between the prevalence of infections and risk factors, including improved water or latrine status at the household or school level.,We estimated the cost-effectiveness of a one-time mass drug administration (MDA) intervention with 75% coverage at the district and EZ levels.,A total of 105,167 students from 1772 schools were surveyed.,The overall egg-positive rates were: Schistosoma haematobium, 5.2%; S. mansoni, 0.06%; and intestinal helminths, 5.47%.,Severe endemic areas were concentrated in East and South Darfur States.,Children living in a house or attending schools with an improved latrine were less likely to be infected with schistosomiasis than those without a latrine (adjusted odds ratio, aOR: 0.45, 95% confidence interval, CI: 0.41-0.51 and aOR: 0.75, 95% CI: 0.70-0.81 at the household or the school levels, respectively).,Open defecation was strongly associated with schistosomiasis (aOR: 1.50, 95% CI: 1.35-1.66).,In community-wide mass treatment at the district level with an 8% threshold for schistosomiasis, 2.2 million people would not benefit from MDA interventions with 75% coverage despite high endemicity, whilst 1.7 million people would receive the MDA intervention unnecessarily.,EZ-level MDA was estimated to be more cost-effective than district-level administration under all circumstances.,Our findings provide updated prevalence figures to guide preventive chemotherapy programmes for schistosomiasis and intestinal helminthiasis in Sudan.,Schistosomiasis was found to be common among the inhabitants of fragile and conflict-affected areas.,In addition, we found that MDA interventions would be more cost-effective at the sub-district level than at the district level, and there was a strong association between schistosomiasis prevalence and latrine status, at both the household and school levels.,This study will help the Sudanese government and its neighbouring countries develop adequate control and elimination strategies.

In Tanzania, the first cases of schistosomiasis were reported in the early 19th century.,Since then, various studies have reported prevalences of up to 100% in some areas.,However, for many years, there have been no sustainable control programmes and systematic data from observational and control studies are very limited in the public domain.,To cover that gap, the present article reviews the epidemiology, malacology, morbidity, and the milestones the country has made in efforts to control schistosomiasis and discusses future control approaches.,The available evidence indicates that, both urinary and intestinal schistosomiasis are still highly endemic in Tanzania and cause significant morbidity.Mass drug administration using praziquantel, currently used as a key intervention measure, has not been successful in decreasing prevalence of infection.,There is therefore an urgent need to revise the current approach for the successful control of the disease.,Clearly, these need to be integrated control measures.

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.

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.

The efficacy of long-lasting insecticidal nets (LLINs) in preventing malaria in Africa is threatened by insecticide resistance.,Bioassays assessing 24-hour mortality post-LLIN exposure have established that resistance to the concentration of pyrethroids used in LLINs is widespread.,However, although mosquitoes may no longer be rapidly killed by LLIN exposure, a delayed mortality effect has been shown to reduce the transmission potential of mosquitoes exposed to nets.,This has been postulated to partially explain the continued efficacy of LLINs against pyrethroid-resistant populations.,Burkina Faso is one of a number of countries with very high malaria burdens and pyrethroid-resistant vectors, where progress in controlling this disease has stagnated.,We measured the impact of LLIN exposure on mosquito longevity in an area of the country with intense pyrethroid resistance to establish whether pyrethroid exposure was still shortening mosquito lifespan in this setting.,We quantified the immediate and delayed mortality effects of LLIN exposure using standard laboratory WHO cone tests, tube bioassays and experimental hut trials on Anopheles gambiae populations originating from the Cascades region of Burkina Faso using survival analysis and a Bayesian state-space model.,Following single and multiple exposures to a PermaNet 2.0 LLIN only one of the four mosquito populations tested showed evidence of delayed mortality.,No delayed mortality was seen in experimental hut studies using LLINs.,A delayed mortality effect was only observed in WHO tube bioassays when deltamethrin concentration was increased above the standard diagnostic dose.,As mosquito pyrethroid-resistance increases in intensity, delayed effects from LLIN exposure are substantially reduced or absent.,Given the rapid increase in resistance occurring in malaria vectors across Africa it is important to determine whether the failure of LLINs to shorten mosquito lifespan is now a widespread phenomenon as this will have important implications for the future of this pivotal malaria control tool.

Long-lasting insecticidal nets (LLINs) and indoor residual spraying of insecticide (IRS) are the primary vector control interventions used to prevent malaria in Africa.,Although both interventions are effective in some settings, high-quality evidence is rarely available to evaluate their effectiveness following deployment by a national malaria control program.,In Uganda, we measured changes in key malaria indicators following universal LLIN distribution in three sites, with the addition of IRS at one of these sites.,Comprehensive malaria surveillance was conducted from October 1, 2011, to March 31, 2016, in three sub-counties with relatively low (Walukuba), moderate (Kihihi), and high transmission (Nagongera).,Between 2013 and 2014, universal LLIN distribution campaigns were conducted in all sites, and in December 2014, IRS with the carbamate bendiocarb was initiated in Nagongera.,High-quality surveillance evaluated malaria metrics and mosquito exposure before and after interventions through (a) enhanced health-facility-based surveillance to estimate malaria test positivity rate (TPR), expressed as the number testing positive for malaria/number tested for malaria (number of children tested for malaria: Walukuba = 42,833, Kihihi = 28,790, and Nagongera = 38,690); (b) cohort studies to estimate the incidence of malaria, expressed as the number of episodes per person-year [PPY] at risk (number of children observed: Walukuba = 340, Kihihi = 380, and Nagongera = 361); and (c) entomology surveys to estimate household-level human biting rate (HBR), expressed as the number of female Anopheles mosquitoes collected per house-night of collection (number of households observed: Walukuba = 117, Kihihi = 107, and Nagongera = 107).,The LLIN distribution campaign substantially increased LLIN coverage levels at the three sites to between 65.0% and 95.5% of households with at least one LLIN.,In Walukuba, over the 28-mo post-intervention period, universal LLIN distribution was associated with no change in the incidence of malaria (0.39 episodes PPY pre-intervention versus 0.20 post-intervention; adjusted rate ratio [aRR] = 1.02, 95% CI 0.36-2.91, p = 0.97) and non-significant reductions in the TPR (26.5% pre-intervention versus 26.2% post-intervention; aRR = 0.70, 95% CI 0.46-1.06, p = 0.09) and HBR (1.07 mosquitoes per house-night pre-intervention versus 0.71 post-intervention; aRR = 0.41, 95% CI 0.14-1.18, p = 0.10).,In Kihihi, over the 21-mo post-intervention period, universal LLIN distribution was associated with a reduction in the incidence of malaria (1.77 pre-intervention versus 1.89 post-intervention; aRR = 0.65, 95% CI 0.43-0.98, p = 0.04) but no significant change in the TPR (49.3% pre-intervention versus 45.9% post-intervention; aRR = 0.83, 95% 0.58-1.18, p = 0.30) or HBR (4.06 pre-intervention versus 2.44 post-intervention; aRR = 0.71, 95% CI 0.30-1.64, p = 0.40).,In Nagongera, over the 12-mo post-intervention period, universal LLIN distribution was associated with a reduction in the TPR (45.3% pre-intervention versus 36.5% post-intervention; aRR = 0.82, 95% CI 0.76-0.88, p < 0.001) but no significant change in the incidence of malaria (2.82 pre-intervention versus 3.28 post-intervention; aRR = 1.10, 95% 0.76-1.59, p = 0.60) or HBR (41.04 pre-intervention versus 20.15 post-intervention; aRR = 0.87, 95% CI 0.31-2.47, p = 0.80).,The addition of three rounds of IRS at ~6-mo intervals in Nagongera was followed by clear decreases in all outcomes: incidence of malaria (3.25 pre-intervention versus 0.63 post-intervention; aRR = 0.13, 95% CI 0.07-0.27, p < 0.001), TPR (37.8% pre-intervention versus 15.0% post-intervention; aRR = 0.54, 95% CI 0.49-0.60, p < 0.001), and HBR (18.71 pre-intervention versus 3.23 post-intervention; aRR = 0.29, 95% CI 0.17-0.50, p < 0.001).,High levels of pyrethroid resistance were documented at all three study sites.,Limitations of the study included the observational study design, the lack of contemporaneous control groups, and that the interventions were implemented under programmatic conditions.,Universal distribution of LLINs at three sites with varying transmission intensity was associated with modest declines in the burden of malaria for some indicators, but the addition of IRS at the highest transmission site was associated with a marked decline in the burden of malaria for all indicators.,In highly endemic areas of Africa with widespread pyrethroid resistance, IRS using alternative insecticide formulations may be needed to achieve substantial gains in malaria control.,In this prospective observational study, Grant Dorsey and colleagues measure changes in malaria burden after long-lasting insecticidal net distribution and indoor residual spraying at three sites of in Uganda.

Emodepside is an anthelmintic, originally developed for veterinary use.,We investigated in healthy subjects the safety, and pharmacokinetics of a liquid service formulation (LSF) and immediate release (IR) tablet of emodepside in 2 randomised, parallel‐group, placebo‐controlled, Phase I studies.,Seventy‐nine subjects in 10 cohorts in the single ascending dose study and 24 subjects in 3 ascending‐dose cohorts in the multiple ascending dose study were enrolled.,Emodepside as LSF was administered orally as single 1-40‐mg doses and for 10 days as 5 or 10 mg once daily and 10‐mg twice daily doses, respectively.,Pharmacokinetics and safety were assessed up to 21 and 30 days, respectively.,In addition, IR tablets containing 5 or 20 mg emodepside were tested in the single ascending dose study.,Emodepside as LSF was rapidly absorbed under fasting conditions, with dose‐proportional increase in plasma concentrations at doses from 1 to 40 mg.,Terminal half‐life was > 500 hours.,In the fed state, emodepside was absorbed more slowly but overall plasma exposure was not significantly affected.,Compared to the LSF, the rate and extent of absorption was significantly lower with the tablets.,Overall, emodepside had acceptable safety and tolerability profiles, no major safety concerns, after single oral administration of 20 mg as LSF and after multiple oral administration over 10 days at 5 and 10 mg OD and at 10 mg twice daily.,For further clinical trials, the development of a tablet formulation overcoming the limitations observed in the present study with the IR tablet formulation is considered.

Few drugs are available for soil-transmitted helminthiasis (STH); the benzimidazoles albendazole and mebendazole are the only drugs being used for preventive chemotherapy as they can be given in one single dose with no weight adjustment.,While generally safe and effective in reducing intensity of infection, they are contra-indicated in first-trimester pregnancy and have suboptimal efficacy against Trichuris trichiura.,In addition, drug resistance is a threat.,It is therefore important to find alternatives.,We searched the literature and the animal health marketed products and pipeline for potential drug development candidates.,Recently registered veterinary products offer advantages in that they have undergone extensive and rigorous animal testing, thus reducing the risk, cost and time to approval for human trials.,For selected compounds, we retrieved and summarised publicly available information (through US Freedom of Information (FoI) statements, European Public Assessment Reports (EPAR) and published literature).,Concomitantly, we developed a target product profile (TPP) against which the products were compared.,The paper summarizes the general findings including various classes of compounds, and more specific information on two veterinary anthelmintics (monepantel, emodepside) and nitazoxanide, an antiprotozoal drug, compiled from the EMA EPAR and FDA registration files.,Few of the compounds already approved for use in human or animal medicine qualify for development track decision.,Fast-tracking to approval for human studies may be possible for veterinary compounds like emodepside and monepantel, but additional information remains to be acquired before an informed decision can be made.

Schistosomiasis is a parasitic disease that affects ∼206 million people globally.,The World Health Organization recently endorsed control of the freshwater snails that host schistosome infectious stages, and here, we show how to better target those snail control efforts.,Schistosomiasis infection occurred on a local scale at our study sites in northwestern Senegal, suggesting that small-scale interventions can suppress transmission.,However, snail clusters were so ephemeral that attempts to target them for removal would be inefficient.,Instead, we found easy-to-measure environmental proxies that were more effective than snail variables at predicting human infections, including area of snail habitat within the site and total site area.,Our work indicates that satellite- or drone-based precision mapping could efficiently identify high-transmission areas.,Recently, the World Health Organization recognized that efforts to interrupt schistosomiasis transmission through mass drug administration have been ineffective in some regions; one of their new recommended strategies for global schistosomiasis control emphasizes targeting the freshwater snails that transmit schistosome parasites.,We sought to identify robust indicators that would enable precision targeting of these snails.,At the site of the world’s largest recorded schistosomiasis epidemic-the Lower Senegal River Basin in Senegal-intensive sampling revealed positive relationships between intermediate host snails (abundance, density, and prevalence) and human urogenital schistosomiasis reinfection (prevalence and intensity in schoolchildren after drug administration).,However, we also found that snail distributions were so patchy in space and time that obtaining useful data required effort that exceeds what is feasible in standard monitoring and control campaigns.,Instead, we identified several environmental proxies that were more effective than snail variables for predicting human infection: the area covered by suitable snail habitat (i.e., floating, nonemergent vegetation), the percent cover by suitable snail habitat, and size of the water contact area.,Unlike snail surveys, which require hundreds of person-hours per site to conduct, habitat coverage and site area can be quickly estimated with drone or satellite imagery.,This, in turn, makes possible large-scale, high-resolution estimation of human urogenital schistosomiasis risk to support targeting of both mass drug administration and snail control efforts.

Human schistosomiasis is a snail-borne parasitic disease affecting more than 200 million people worldwide.,Direct contact with snail-infested freshwater is the primary route of exposure.,Water management infrastructure, including dams and irrigation schemes, expands snail habitat, increasing the risk across the landscape.,The Diama Dam, built on the lower basin of the Senegal River to prevent saltwater intrusion and promote year-round agriculture in the drought-prone Sahel, is a paradigmatic case.,Since dam completion in 1986, the rural population-whose livelihoods rely mostly on agriculture-has suffered high rates of schistosome infection.,The region remains one of the most hyperendemic regions in the world.,Because of the convergence between livelihoods and environmental conditions favorable to transmission, schistosomiasis is considered an illustrative case of a disease-driven poverty trap (DDPT).,The literature to date on the topic, however, remains largely theoretical.,With qualitative data generated from 12 focus groups in four villages, we conducted team-based theme analysis to investigate how perception of schistosomiasis risk and reported preventive behaviors may suggest the presence of a DDPT.,Our analysis reveals three key findings: 1) rural villagers understand schistosomiasis risk (i.e., where and when infections occur), 2) accordingly, they adopt some preventive behaviors, but ultimately, 3) exposure persists, because of circumstances characteristic of rural livelihoods.,These findings highlight the capacity of local populations to participate actively in schistosomiasis control programs and the limitations of widespread drug treatment campaigns.,Interventions that target the environmental reservoir of disease may provide opportunities to reduce exposure while maintaining resource-dependent livelihoods.

It is believed that the current prevalence of malaria in endemic areas reflects selection for the carrier form of sickle cell trait through a survival advantage.,Malaria has been incriminated as a great cause of mortality in people with sickle cell disease (SCD).,However, people with SCD, a high-risk group, do not benefit from free or subsisized malaria prevention and treatment in Cameroon unlike other vulnerable groups which may be due to insufficient evidence to guide policy makers.,This study aimed at describing clinical and socio-demographic characteristics of patients with malaria, determining the prevalence of malaria in hospitalized children and in those with SCD and without, compare frequency of presentation of malaria related complications (using clinical and laboratory elements that define severe malaria) between children admitted for malaria with SCD and those without and finally, determing the risk factors for death in children admitted for malaria.,This was a retrospective analysis of admission records of children age 1 to 18 years with a confirmed malaria diagnosis admitted at the Laquintinie Hospital during January 2015 through December 2018.,Clinical features, laboratory characteristics and outcome of malarial infections, stratified by SCD status were studied.,Patients with HIV infection, malnutrition, renal failure and discharged against medical advice were excluded from the study.,Data were analysed using Epi-info 7 software and analysis done.,Chi square test, Odds ratios, CI and student’s t test were used to determine association between variables.,Statistical significance was set at p-value ≤0.05.,The prevalence of malaria was lower among children with SCD than it was among children without SCD (23.5% vs 44.9%).,Similarly, among those with a positive microscopy, the mean parasite density was significantly lower among children with SCD than it was among children without SCD (22,875.6 vs 57,053.6 parasites/ μl with t-value − 3.2, p-value 0.002).,The mean hemoglobin concentration was lower in SCD as compared to non SCD (5.7 g/l vs 7.4 g/l, t-value − 12.5, p-value < 0.001).,Overall mortality in SCD was 3.4% and malaria was reponsible for 20.4% of these deaths as compared to the 35.4% in non SCD patients.,Convulsion and impaired consciousness were significantly lower in SCD group (OR:0.1, CI: 0.1-0.3, p value < 0.01 and OR:0.1, CI:0.1-0.2, p-value < 0.001 respectively).,Death was significantly higher in SCD patients with malaria as compared to SCD patients admitted for other pathologies (3.2% vs 1.5%., OR:2.2, CI:1-5, p-value 0.050).,The SCD population has a lower mortality related to malaria compared to the non-SCD population.,Meanwhile, within the SCD population, those admitted with malaria are twice more likely to die than those admitted for other pathologies.,Jaundice, hepatomegaly and splenomegaly were common in SCD with malaria, however no risk factors for malaria severity or malaria related death was identified.

Plasmodium falciparum, the most virulent agent of human malaria, shares a recent common ancestor with the gorilla parasite P. praefalciparum.,Little is known about the other gorilla and chimpanzee-infecting species in the same (Laverania) subgenus as P. falciparum but none of them are capable of establishing repeated infection and transmission in humans.,To elucidate underlying mechanisms and the evolutionary history of this subgenus, we have generated multiple genomes from all known Laverania species.,The completeness of our dataset allows us to conclude that interspecific gene transfers as well as convergent evolution were important in the evolution of these species.,Striking copy number and structural variations were observed within gene families and one, stevor shows a host specific sequence pattern.,The complete genome sequence of the closest ancestor of P. falciparum enables us to estimate the timing of the beginning of speciation to be 40,000-60,000 years ago followed by a population bottleneck around 4,000-6,000 years ago.,Our data allow us also to search in detail for the features of P. falciparum that made it the only member of the Laverania able to infect and spread in humans.

Accurate diagnosis of urogenital schistosomiasis is crucial for disease surveillance and control.,Routine diagnostic methods, however, lack sensitivity when assessing patients with low levels of infection still able to maintain pathogen transmission.,Therefore, there is a need for highly sensitive diagnostic tools that can be used at the point-of-care in endemic areas.,Recombinase polymerase amplification (RPA) is a rapid and sensitive diagnostic tool that has been used to diagnose several pathogens at the point-of-care.,Here, the analytical performance of a previously developed RPA assay (RT-ShDra1-RPA) targeting the Schistosoma haematobium Dra1 genomic region was assessed using commercially synthesised S. haematobium Dra1 copies and laboratory-prepared samples spiked with S. haematobium eggs.,Clinical performance was also assessed by comparing diagnostic outcomes with that of a reference diagnostic standard, urine-egg microscopy.,The RT-ShDra1-RPA was able to detect 1 × 101 copies of commercially synthesised Dra1 DNA as well as one S. haematobium egg within laboratory-spiked ddH2O samples.,When compared with urine-egg microscopy, the overall sensitivity and specificity of the RT-ShDra1-RPA assay was 93.7% (±88.7-96.9) and 100% (±69.1-100), respectively.,Positive and negative predictive values were 100% (±97.5-100) and 50% (±27.2-72.8), respectively.,The RT-ShDra1-RPA therefore shows promise as a rapid and highly sensitive diagnostic tool able to diagnose urogenital schistosomiasis at the point-of-care.

Kato-Katz examination of stool smears is the field-standard method for detecting Schistosoma mansoni infection.,However, Kato-Katz misses many active infections, especially of light intensity.,Point-of-care circulating cathodic antigen (CCA) is an alternative field diagnostic that is more sensitive than Kato-Katz when intensity is low, but interpretation of CCA-trace results is unclear.,To evaluate trace results, we tested urine and stool specimens from 398 pupils from eight schools in Burundi using four approaches: two in Burundi and two in a laboratory in Leiden, the Netherlands.,In Burundi, we used Kato-Katz and point-of-care CCA (CCAB).,In Leiden, we repeated the CCA (CCAL) and also used Up-Converting Phosphor Circulating Anodic Antigen (CAA).,We applied Bayesian latent class analyses (LCA), first considering CCA traces as negative and then as positive.,We used the LCA output to estimate validity of the prevalence estimates of each test in comparison to the population-level infection prevalence and estimated the proportion of trace results that were likely true positives.,Kato-Katz yielded the lowest prevalence (6.8%), and CCAB with trace considered positive yielded the highest (53.5%).,There were many more trace results recorded by CCA in Burundi (32.4%) than in Leiden (2.3%).,Estimated prevalence with CAA was 46.5%.,LCA indicated that Kato-Katz had the lowest sensitivity: 15.9% [Bayesian Credible Interval (BCI): 9.2-23.5%] with CCA-trace considered negative and 15.0% with trace as positive (BCI: 9.6-21.4%), implying that Kato-Katz missed approximately 85% of infections.,CCAB underestimated disease prevalence when trace was considered negative and overestimated disease prevalence when trace was considered positive, by approximately 12 percentage points each way, and CAA overestimated prevalence in both models.,Our results suggest that approximately 52.2% (BCI: 37.8-5.8%) of the CCAB trace readings were true infections.,Whether measured in the laboratory or the field, CCA outperformed Kato-Katz at the low infection intensities in Burundi.,CCA with trace as negative likely missed many infections, whereas CCA with trace as positive overestimated prevalence.,In the absence of a field-friendly gold standard diagnostic, the use of a variety of diagnostics with differing properties will become increasingly important as programs move towards elimination of schistosomiasis.,It is clear that CCA is a valuable tool for the detection and mapping of S. mansoni infection in the field and CAA may be a valuable field tool in the future.,The online version of this article (10.1186/s13071-018-2700-4) contains supplementary material, which is available to authorized users.

The use of primaquine (PQ) for radical treatment of Plasmodium vivax in carriers of G6PD deficiency (G6PDd) constitutes the main factor associated with severe haemolysis in G6PDd.,The current study aimed to estimate the incremental cost-effectiveness ratio of using a rapid diagnostic test (RDT) to detect G6PDd in male patients with P.vivax malaria in the Brazilian Amazon, in comparison with the routine indicated by the Programme for Malaria Control, which does not include this evaluation.,A cost-effectiveness analysis of estimated RDT use was carried out for the Brazilian Amazon for the year 2013, considering the perspective of the Brazilian Public Health System.,Using decision trees, estimates were compared for two different RDT strategies for G6PDd in male individuals infected with P. vivax before being prescribed PQ, with the routine indicated in Brazil, which does not include prior diagnosis of G6PDd.,The first strategy considered the combined use of RDT BinaxNOW® G6PD (BX-G6PD) in municipalities with more than 100,000 inhabitants and the routine programme (RP) for the other municipalities.,Operational limitations related to the required temperature control and venous blood collection currently restrict the use of RDT BX-G6PD in small municipalities.,The second strategy considered the use of the RDT CareStart™ G6PD (CS-G6PD) in 100 % of the municipalities.,The analysis was carried out for the outcomes: “adequately diagnosed case” and “hospitalization avoided”.,For the outcome “adequately diagnosed case”, comparing the RDT strategies based on RDT with the routine control programme (RP), the CS-G6PD strategy was the most cost-effective, with BX-G6PD extendedly dominating (the ICER of BX-G6PD compared with RP was higher than the ICER of CS-G6PD compared with RP).,CS-G6PD dominated the other strategies for the “hospitalization avoided” outcome.,The CS-G6PD strategy is cost-effective for adequately diagnosing cases and avoiding hospitalization.,This information can help in decision-making, both in incorporating prior diagnosis in the use of PQ and to promote greater safety among G6PD deficient individuals in the Brazilian Amazon P. vivax endemic areas.

Plasmodium vivax causes almost half of all malaria cases in Asia and is recognised as a significant cause of morbidity.,In recent years it has been associated with severe and fatal disease.,The extent to which P. vivax contributes to death is not known.,To define the epidemiology of mortality attributable to vivax malaria in southern Papua, Indonesia, a retrospective clinical records-based audit was conducted of all deaths in patients with vivax malaria at a tertiary referral hospital.,Between January 2004 and September 2009, hospital surveillance identified 3,495 inpatients with P. vivax monoinfection and 65 (1.9%) patients who subsequently died.,Charts for 54 of these 65 patients could be reviewed, 40 (74%) of whom had pure P. vivax infections on cross-checking.,Using pre-defined conservative criteria, vivax malaria was the primary cause of death in 6 cases, a major contributor in 17 cases and a minor contributor in a further 13 cases.,Extreme anaemia was the most common primary cause of death.,Malnutrition, sepsis with respiratory and gastrointestinal manifestations, and chronic diseases were the commonest attributed causes of death for patients in the latter two categories.,There were an estimated 293,763 cases of pure P. vivax infection in the community during the study period giving an overall minimum case fatality of 0.12 per 1,000 infections.,The corresponding case fatality in hospitalised patients was 10.3 per 1,000 infections.,Although uncommonly directly fatal, vivax malaria is an important indirect cause of death in southern Papua in patients with malnutrition, sepsis syndrome and chronic diseases, including HIV infection.,The online version of this article (doi:10.1186/s12916-014-0217-z) contains supplementary material, which is available to authorized users.

Background.,The World Health Organization recommends that all malaria management be based on parasitological identification.,We monitored performance of trained community health workers (CHWs) in adhering to this recommendation to restrict artemisinin-based combination therapies (ACTs) to positive rapid diagnostic test (RDT)-confirmed cases in children in 3 malaria-endemic sub-Saharan African countries.,Methods.,In 33 villages in Burkina Faso, 45 villages in Nigeria, and 84 villages in Uganda, 265 CHWs were trained over a minimum of 3 days to diagnose malaria using RDTs (prepare, read, record results, and inform the patient about results) and treat RDT-confirmed uncomplicated malaria cases with ACTs.,In Nigeria, CHWs were also taught to obtain a thick blood smear.,Spent RDT kits and prepared blood slides were collected and interpreted independently in Burkina Faso and Nigeria to confirm CHWs' diagnoses.,Interviews were held with 12 of 17 CHWs who prescribed ACTs for patients with RDT-negative test results, and with 16 of 29 caregivers to determine factors related to noncompliance.,Results.,Of 12 656 patients treated with ACTs in the participating countries (5365 in Burkina Faso, 1648 in Nigeria, and 5643 in Uganda), 29 patients (8 from Burkina Faso, 17 from Nigeria, 4 from Uganda) were RDT negative.,The small number of RDT-negative ACT-treated cases limits statistical analysis.,Only a few CHWs were involved, and they were more likely to be traders rather than farmers (odds ratio [OR], 6.15; 95% confidence interval [CI], 2.09-18.07; P = .0004).,RDT-negative children who were treated with ACTs had a significantly higher probability of residing in a village other than that of the CHW (OR, 3.85; 95% CI, 1.59-9.30; P = .0018).,Parental pressure was identified in interviews with parents.,Conclusions.,Noncompliance with results of RDT tests is relatively rare when CHWs are trained and well supervised.,Clinical Trials Registration.,ISRCTN13858170.

The focus of India’s National Malaria Programme witnessed a paradigm shift recently from health facility to community-based approaches.,The current thrust is on diagnosing and treating malaria by community health workers and prevention through free provision of long-lasting insecticidal nets.,However, appropriate community awareness and practice are inevitable for the effectiveness of such efforts.,In this context, the study assessed community perceptions and practice on malaria and similar febrile illnesses.,This evidence base is intended to direct the roll-out of the new strategies and improve community acceptance and utilization of services.,A qualitative study involving 26 focus group discussions and 40 key informant interviews was conducted in two districts of Odisha State in India.,The key points of discussion were centred on community perceptions and practice regarding malaria prevention and treatment.,Thematic analysis of data was performed.,The 272 respondents consisted of 50% females, three-quarter scheduled tribe community and 30% students.,A half of them were literates.,Malaria was reported to be the most common disease in their settings with multiple modes of transmission by the FGD participants.,Adoption of prevention methods was seasonal with perceived mosquito density.,The reported use of bed nets was low and the utilization was determined by seasonality, affordability, intoxication and alternate uses of nets.,Although respondents were aware of malaria-related symptoms, care-seeking from traditional healers and unqualified providers was prevalent.,The respondents expressed lack of trust in the community health workers due to frequent drug stock-outs.,The major determinants of health care seeking were socio-cultural beliefs, age, gender, faith in the service provider, proximity, poverty, and perceived effectiveness of available services.,Apart from the socio-cultural and behavioural factors, the availability of acceptable care can modulate the community perceptions and practices on malaria management.,The current community awareness on symptoms of malaria and prevention is fair, yet the prevention and treatment practices are not optimal.,Promoting active community involvement and ownership in malaria control and management through strengthening community based organizations would be relevant.,Further, timely availability of drugs and commodities at the community level can improve their confidence in the public health system.

Recent studies in Southeast Asia have demonstrated substantial zoonotic transmission of Plasmodium knowlesi to humans.,Microscopically, P. knowlesi exhibits several stage-dependent morphological similarities to P. malariae and P. falciparum.,These similarities often lead to misdiagnosis of P. knowlesi as either P. malariae or P. falciparum and PCR-based molecular diagnostic tests are required to accurately detect P. knowlesi in humans.,The most commonly used PCR test has been found to give false positive results, especially with a proportion of P. vivax isolates.,To address the need for more sensitive and specific diagnostic tests for the accurate diagnosis of P. knowlesi, we report development of a new single-step PCR assay that uses novel genomic targets to accurately detect this infection.,We have developed a bioinformatics approach to search the available malaria parasite genome database for the identification of suitable DNA sequences relevant for molecular diagnostic tests.,Using this approach, we have identified multi-copy DNA sequences distributed in the P. knowlesi genome.,We designed and tested several novel primers specific to new target sequences in a single-tube, non-nested PCR assay and identified one set of primers that accurately detects P. knowlesi.,We show that this primer set has 100% specificity for the detection of P. knowlesi using three different strains (Nuri, H, and Hackeri), and one human case of malaria caused by P. knowlesi.,This test did not show cross reactivity with any of the four human malaria parasite species including 11 different strains of P. vivax as well as 5 additional species of simian malaria parasites.,The new PCR assay based on novel P. knowlesi genomic sequence targets was able to accurately detect P. knowlesi.,Additional laboratory and field-based testing of this assay will be necessary to further validate its utility for clinical diagnosis of P. knowlesi.

Modelling is widely used to inform decisions about management of malaria and acute febrile illnesses.,Most models depend on estimates of the probability that untreated patients with malaria or bacterial illnesses will progress to severe disease or death.,However, data on these key parameters are lacking and assumptions are frequently made based on expert opinion.,Widely diverse opinions can lead to conflicting outcomes in models they inform.,A Delphi survey was conducted with malaria experts aiming to reach consensus on key parameters for public health and economic models, relating to the outcome of untreated febrile illnesses.,Survey questions were stratified by malaria transmission intensity, patient age, and HIV prevalence.,The impact of the variability in opinion on decision models is illustrated with a model previously used to assess the cost-effectiveness of malaria rapid diagnostic tests.,Some consensus was reached around the probability that patients from higher transmission settings with untreated malaria would progress to severe disease (median 3%, inter-quartile range (IQR) 1-5%), and the probability that a non-malaria illness required antibiotics in areas of low HIV prevalence (median 20%).,Children living in low transmission areas were considered to be at higher risk of progressing to severe malaria (median 30%, IQR 10-58%) than those from higher transmission areas (median 13%, IQR 7-30%).,Estimates of the probability of dying from severe malaria were high in all settings (medians 60-73%).,However, opinions varied widely for most parameters, and did not converge on resurveying.,This study highlights the uncertainty around potential consequences of untreated malaria and bacterial illnesses.,The lack of consensus on most parameters, the wide range of estimates, and the impact of variability in estimates on model outputs, demonstrate the importance of sensitivity analysis for decision models employing expert opinion.,Results of such models should be interpreted cautiously.,The diversity of expert opinion should be recognised when policy options are debated.

A current need in the global effort to eliminate lymphatic filariasis (LF) is the availability of reliable diagnostic tools that can be used to guide programmatic decisions, especially decisions made in the final stages of the program.,This study conducted in The Gambia aimed to assess antifilarial antibody levels among populations living in historically highly LF-endemic areas and to evaluate the use of serologic tools to confirm the interruption of LF transmission.,A total of 2,612 dried blood spots (DBSs) collected from individuals aged 1 year and above from 15 villages were tested for antibodies to Wb123 by enzyme-linked immunosorbent assay (ELISA).,A subset of DBS (N = 599) was also tested for antibodies to Bm14 by ELISA.,Overall, the prevalence of Wb123 was low (1.5%, 95% confidence interval [CI] 1.1-2.1%).,In 7 of 15 villages (46.7%), there were no Wb123-positive individuals identified.,Individuals with positive responses to Wb123 ranged in age from 3 to 100 years.,Overall, Bm14 prevalence was also low (1.5%, 95% CI 0.7-2.8%).,Bm14 positivity was significantly associated with older age (P < 0.001).,The low levels of antibody responses to Wb123 observed in our study strongly suggest that sustainable LF transmission has likely ceased in The Gambia.,In addition, our results support the conclusion that serologic tools can have a role in guiding programmatic decision making and supporting surveillance.

Current WHO recommendations for lymphatic filariasis (LF) surveillance advise programs to implement activities to monitor for new foci of transmission after stopping mass drug administration (MDA).,A current need in the global effort to eliminate LF is to standardize diagnostic tools and surveillance activities beyond the recommended transmission assessment survey (TAS).,TAS was first conducted in American Samoa in 2011 (TAS 1) and a repeat TAS was carried out in 2015 (TAS 2).,Circulating filarial antigen (CFA) and serologic results from both surveys were analyzed to determine whether interruption of LF transmission has been achieved in American Samoa.,A total of 1,134 and 864 children (5-10 years old) were enrolled in TAS 1 and TAS 2, respectively.,Two CFA-positive children were identified in TAS 1, and one CFA-positive child was identified in TAS 2.,Results of both surveys were below the threshold for which MDA was warranted.,Additionally, 1,112 and 836 dried blood spots from TAS 1 and TAS 2, respectively were tested for antibodies to Wb123, Bm14 and Bm33 by luciferase immunoprecipitation system (LIPS) assay and multiplex bead assay.,In 2011, overall prevalence of responses to Wb123, Bm14, and Bm33 was 1.0%, 6.8% and 12.0%, respectively.,In 2015, overall prevalence of positive Bm14 and Bm33 responses declined significantly to 3.0% (p<0.001) and 7.8% (p = 0.013), respectively.,Although passing TAS 1 and TAS 2 and an overall decline in the prevalence of antibodies to Bm14 and Bm33 between these surveys suggests decreased exposure and infection among young children, there were persistent responses in some schools.,Clustering and persistence of positive antibody responses in schools may be an indication of ongoing transmission.,There is a need to better understand the limitations of current antibody tests, but our results suggest that serologic tools can have a role in guiding programmatic decision making.

The Gran Chaco ecoregion, a hotspot for Chagas and other neglected tropical diseases, is home to >20 indigenous peoples.,Our objective was to identify the main ecological and sociodemographic determinants of house infestation and abundance of Triatoma infestans in traditional Qom populations including a Creole minority in Pampa del Indio, northeastern Argentina.,A cross-sectional survey determined house infestation by timed-manual searches with a dislodging aerosol in 386 inhabited houses and administered questionnaires on selected variables before full-coverage insecticide spraying and annual vector surveillance.,We fitted generalized linear models to two global models of domestic infestation and bug abundance, and estimated coefficients via multimodel inference with model averaging.,Most Qom households were larger and lived in small-sized, recently-built, precarious houses with fewer peridomestic structures, and fewer livestock and poultry than Creoles’.,Qom households had lower educational level and unexpectedly high residential mobility.,House infestation (31.9%) was much lower than expected from lack of recent insecticide spraying campaigns and was spatially aggregated.,Nearly half of the infested houses examined had infected vectors.,Qom households had higher prevalence of domestic infestation (29.2%) than Creoles’ (10.0%), although there is large uncertainty around the adjusted OR.,Factors with high relative importance for domestic infestation and/or bug abundance were refuge availability, distance to the nearest infested house, domestic insecticide use, indoor presence of poultry, residential overcrowding, and household educational level.,Our study highlights the importance of sociodemographic determinants of domestic infestation such as overcrowding, education and proximity to the nearest infested house, and corroborates the role of refuge availability, domestic use of insecticides and household size.,These factors may be used for designing improved interventions for sustainable disease control and risk stratification.,Housing instability, household mobility and migration patterns are key to understanding the process of house (re)infestation in the Gran Chaco.

Non-domiciliated (intrusive) triatomine vectors remain a challenge for the sustainability of Chagas disease vector control as these triatomines are able to transiently (re-)infest houses.,One of the best-characterized examples is Triatoma dimidiata from the Yucatan peninsula, Mexico, where adult insects seasonally infest houses between March and July.,We focused our study on three rural villages in the state of Yucatan, Mexico, in which we performed a situation analysis as a first step before the implementation of an ecohealth (ecosystem approach to health) vector control intervention.,The identification of the key determinants affecting the transient invasion of human dwellings by T. dimidiata was performed by exploring associations between bug presence and qualitative and quantitative variables describing the ecological, biological and social context of the communities.,We then used a participatory action research approach for implementation and evaluation of a control strategy based on window insect screens to reduce house infestation by T. dimidiata.,This ecohealth approach may represent a valuable alternative to vertically-organized insecticide spraying.,Further evaluation may confirm that it is sustainable and provides effective control (in the sense of limiting infestation of human dwellings and vector/human contacts) of intrusive triatomines in the region.

Vaccine-induced immunity depends on long-lived plasma cells (LLPCs) that maintain antibody levels.,A recent mouse study showed that Plasmodium chaubaudi infection reduced pre-existing influenza-specific antibodies-raising concerns that malaria may compromise pre-existing vaccine responses.,We extended these findings to P. yoelii infection, observing decreases in antibodies to model antigens in inbred mice and to influenza in outbred mice, associated with LLPC depletion and increased susceptibility to influenza rechallenge.,We investigated the implications of these findings in Malian children by measuring vaccine-specific IgG (tetanus, measles, hepatitis B) before and after the malaria-free 6-month dry season, 10 days after the first malaria episode of the malaria season, and after the subsequent dry season.,On average, vaccine-specific IgG did not decrease following acute malaria.,However, in some children malaria was associated with an accelerated decline in vaccine-specific IgG, underscoring the need to further investigate the impact of malaria on pre-existing vaccine-specific antibodies.

Studies in malaria patients indicate that higher frequencies of peripheral blood CD4+ Foxp3+ CD25+ regulatory T (Treg) cells correlate with increased blood parasitemia.,This observation implies that Treg cells impair pathogen clearance and thus may be detrimental to the host during infection.,In C57BL/6 mice infected with Plasmodium berghei ANKA, depletion of Foxp3+ cells did not improve parasite control or disease outcome.,In contrast, elevating frequencies of natural Treg cells in vivo using IL-2/anti-IL-2 complexes resulted in complete protection against severe disease.,This protection was entirely dependent upon Foxp3+ cells and resulted in lower parasite biomass, impaired antigen-specific CD4+ T and CD8+ T cell responses that would normally promote parasite tissue sequestration in this model, and reduced recruitment of conventional T cells to the brain.,Furthermore, Foxp3+ cell-mediated protection was dependent upon CTLA-4 but not IL-10.,These data show that T cell-mediated parasite tissue sequestration can be reduced by regulatory T cells in a mouse model of malaria, thereby limiting malaria-induced immune pathology.

Sri Lanka has a long history of malaria control, and over the past decade has had dramatic declines in cases amid a national conflict.,A case study of Sri Lanka's malaria programme was conducted to characterize the programme and explain recent progress.,The case study employed qualitative and quantitative methods.,Data were collected from published and grey literature, district-level and national records, and thirty-three key informant interviews.,Expenditures in two districts for two years - 2004 and 2009 - were compiled.,Malaria incidence in Sri Lanka has declined by 99.9% since 1999.,During this time, there were increases in the proportion of malaria infections due to Plasmodium vivax, and the proportion of infections occurring in adult males.,Indoor residual spraying and distribution of long-lasting insecticide-treated nets have likely contributed to the low transmission.,Entomological surveillance was maintained.,A strong passive case detection system captures infections and active case detection was introduced.,When comparing conflict and non-conflict districts, vector control and surveillance measures were maintained in conflict areas, often with higher coverage reported in conflict districts.,One of two districts in the study reported a 48% decline in malaria programme expenditure per person at risk from 2004 to 2009.,The other district had stable malaria spending.,Malaria is now at low levels in Sri Lanka - 124 indigenous cases were found in 2011.,The majority of infections occur in adult males and are due to P. vivax.,Evidence-driven policy and an ability to adapt to new circumstances contributed to this decline.,Malaria interventions were maintained in the conflict districts despite an ongoing war.,Sri Lanka has set a goal of eliminating malaria by the end of 2014.,Early identification and treatment of infections, especially imported ones, together with effective surveillance and response, will be critical to achieving this goal.

Jose Najera and colleagues identify lessons from the Global Malaria Eradication Programme (1955-1969) relevant to current elimination and eradication efforts.,Encouraged by the early success of using dichloro-diphenyl-trichloroethane (DDT) against malaria, the World Health Organization (WHO) embarked on the Global Malaria Eradication Program (GMEP) in 1955.,Fourteen years later, the campaign was discontinued when it was recognised that eradication was not achievable with the available means in many areas, although the long-term goal remained unchanged.,During the GMEP, malaria was permanently eliminated from many regions.,In other areas, however, substantial gains were lost in resurgences, sometimes of epidemic proportions.,During the 1970s and 1980s, because of economic and financial crises, international support for malaria control declined rapidly, but in the past decade, following increasing demands from endemic countries and promising results from scaling up of control activities, interest in malaria elimination and the long-term goal of eradication has received international political and financial support.,In 2007, there was a renewed call for malaria eradication and a consultative process to define a research and development agenda for malaria eradication (malERA) was established.,Lessons learned from the GMEP (1955-1969) highlight the fact that no single strategy can be applicable everywhere and that a long-term commitment with a flexible strategy that includes community involvement, integration with health systems, and the development of agile surveillance systems is needed.

Cellular aging is difficult to study in individuals with natural infection, given the diversity of symptom duration and clinical presentation, and the high interference of aging-related processes with host and environmental factors.,To address this challenge, we took advantage of the controlled human malaria infection (CHMI) model.,This approach allowed us to characterize the relationship among cellular aging markers prior, during and post malaria pathophysiology in humans, controlling for infection dose, individual heterogeneity, previous exposure and co-infections.,We demonstrate that already low levels of Plasmodium falciparum impact cellular aging by inducing high levels of inflammation and redox-imbalance; and that cellular senescence reversed after treatment and parasite clearance.,This study provides insights into the complex relationship of telomere length, cellular senescence, telomerase expression and aging-related processes during a single malaria infection.

After a century of constant failure to produce an in vitro culture of the most widespread human malaria parasite Plasmodium vivax, recent advances have highlighted the difficulties to provide this parasite with a healthy host cell to invade, develop, and multiply under in vitro conditions.,The actual level of understanding of the heterogeneous populations of cells-framed under the name ‘reticulocytes’-and, importantly, their adequate in vitro progression from very immature reticulocytes to normocytes (mature erythrocytes) is far from complete.,The volatility of its individual stability may suggest the reticulocyte as a delusory cell, particularly to be used for stable culture purposes.,Yet, the recent relevance gained by a specific subset of highly immature reticulocytes has brought some hope.,Very immature reticulocytes are characterized by a peculiar membrane harboring a plethora of molecules potentially involved in P. vivax invasion and by an intracellular complexity dynamically changing upon its quick maturation into normocytes.,We analyze the potentialities offered by this youngest reticulocyte subsets as an ideal in vitro host cell for P. vivax.

Lung complications during malaria infection can range from coughs and impairments in gas transfer to the development of acute respiratory distress syndrome (ARDS).,Infecting C57BL/6 mice with Plasmodium berghei K173 strain (PbK) resulted in pulmonary oedema, capillaries congested with leukocytes and infected red blood cells (iRBCs), and leukocyte infiltration into the lungs.,This new model of malaria-associated lung pathology, without any accompanying cerebral complications, allows the investigation of mechanisms leading to the lung disease.,The activity of the amiloride-sensitive epithelial sodium channel (ENaC) in alveolar epithelial cells is decreased by several respiratory tract pathogens and this is suggested to contribute to pulmonary oedema.,We show that PbK, a pathogen that remains in the circulation, also decreased the activity and expression of ENaC, suggesting that infectious agents can have indirect effects on ENaC activity in lung epithelial cells.,The reduced ENaC activity may contribute to the pulmonary oedema induced by PbK malaria.

Sequestration of Plasmodium falciparum-infected erythrocytes in host blood vessels is a key triggering event in the pathogenesis of severe childhood malaria, which is responsible for about one million deaths every year1.,Sequestration is mediated by specific interactions between members of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family and receptors on the endothelial lining2.,Severe malaria is associated with expression of specific PfEMP1 subtypes containing domain cassettes (DC) 8 and 133, but the endothelial receptor for parasites expressing these proteins was unknown4,5.,Here, we identify endothelial protein C receptor (EPCR), which mediates cytoprotective effects of activated protein C6, as the endothelial receptor for DC8 and DC13 PfEMP1.,We show that EPCR binding is mediated through the N-terminal cysteine-rich interdomain region (CIDRα1) of DC8 and group A PfEMP1 subfamilies and that CIDRα1 interferes with protein C binding to EPCR.,This PfEMP1 adhesive property links P. falciparum cytoadhesion to a host receptor involved in anticoagulation and endothelial cytoprotective pathways and has implications for understanding malaria pathology and the development of new malaria interventions.

Historically, malaria had been a widespread disease in China.,A national plan was launched in China in 2010, aiming to eliminate malaria by 2020.,In 2017, no indigenous cases of malaria were detected in China for the first time.,To provide evidence for precise surveillance and response to achieve elimination goal, a comprehensive study is needed to determine the changing epidemiology of malaria and the challenges towards elimination.,Using malaria surveillance data from 2011 to 2016, an integrated series of analyses was conducted to elucidate the changing epidemiological features of autochthonous and imported malaria, and the spatiotemporal patterns of malaria importation from endemic countries.,From 2011 to 2016, a total of 21,062 malaria cases with 138 deaths were reported, including 91% were imported and 9% were autochthonous.,The geographic distribution of local transmission have shrunk dramatically, but there were still more than 10 counties reporting autochthonous cases in 2013-2016, particularly in counties bordering with countries in South-East Asia.,The importation from 68 origins countries had an increasing annual trend from Africa but decreasing importation from Southeast Asia.,Four distinct communities have been identified in the importation networks with the destinations in China varied by origin and species.,China is on the verge of malaria elimination, but the residual transmission in border regions and the threats of importation from Africa and Southeast Asia are the key challenges to achieve and maintain malaria elimination.,Efforts from China are also needed to help malaria control in origin countries and reduce the risk of introduced transmission.,The online version of this article (10.1186/s12936-019-2736-8) contains supplementary material, which is available to authorized users.

Malaria within the Greater Mekong sub-region is extremely heterogeneous.,While China and Thailand have been relatively successful in controlling malaria, Myanmar continues to see high prevalence.,Coupled with the recent emergence of artemisinin-resistant malaria along the Thai-Myanmar border, this makes Myanmar an important focus of malaria within the overall region.,However, accurate epidemiological data from Myanmar have been lacking, in part because of ongoing and emerging conflicts between the government and various ethnic groups.,Here the results are reported from a risk analysis of malaria slide positivity in a conflict zone along the China-Myanmar border.,Surveys were conducted in 13 clinics and hospitals around Laiza City, Myanmar between April 2011 and October 2012.,Demographic, occupational and educational information, as well as malaria infection history, were collected.,Logistic models were used to assess risk factors for slide positivity.,Age patterns in Plasmodium vivax infections were younger than those with Plasmodium falciparum.,Furthermore, males were more likely than females to have falciparum infections.,Patients who reported having been infected with malaria during the previous year were much more likely to have a current vivax infection.,During the second year of the study, falciparum infections among soldiers increased signficiantly.,These results fill some knowledge gaps with regard to risk factors associated with malaria slide positivity in this conflict region of north-eastern Myanmar.,Since epidemiological studies in this region have been rare or non-existent, studies such as the current are crucial for understanding the dynamic nature of malaria in this extremely heterogeneous epidemiological landscape.

Recently, exploratory spatial data analysis is for problem solving, hypothesis generation and knowledge construction.,Unless geographically weighted regression, sophisticated spatial regression models best control spatial heterogeneity in outcomes and the associated risk factors but cannot visually display and identify areas of the significant associations.,The under-utilised excess risk maps (ERMs) and conditioned choropleth maps (CCMs) are useful to address this issue and simplify epidemiological information to public health stakeholders without much statistical backgrounds.,Using malaria and sociodemographic determinants in Ghana as case study, this paper applied ERM and CCM techniques for identification of areas at elevated risk of disease-risk factor co-location.,We computed and smoothed mean district-specific malaria incidences for the period 2010 to 2014 as a function of sociodemographic determinants.,The spatial distribution of malaria was investigated through global and local spatial autocorrelations, and the association with sociodemographic risk factors evaluated with bivariate correlations.,ERMs and CCMs were produced for the statistically significant risk factors.,The incidence of malaria increased over time with cluster locations detected, predominantly at the northern parts but later few spread to the middle parts of the country.,Our results suggested that with respect to sociodemographic determinants, district variations in malaria rates might be explained by inequalities in seven sociodemographics, including an unexpected significant negative association with non-religious affiliation.,The sociodemographics had positive spatial autocorrelations, exhibited statistically significant interactions and the strongest was observed in urbanisation-basic education correlation (p< 0.01, r = +0.969).,The ERMs and CCMs specifically identified locations with lower or higher than expected rates with respect to particular risk factor(s) where improving risk factor(s) such as employment-to-population ratio in rural areas, basic education could have cascade effects to reduce the expected malaria incidence in endemic areas.,Ghana remains malaria hyperendemic region with district-level spatial heterogeneity.,Significant association between malaria and sociodemographics was detected and the ERMs and CCMs geo-visually pinpointed locations of these significant associations.,To complement sophisticated spatial regression models, the easily interpretable ERMs and CCMs could be used to specify where disease-risk factor associations are significant, simplifying complex spatial epidemiological information for efficient public health administration.

There is a need for comprehensive evaluations of the underlying local factors that contribute to residual malaria in sub-Saharan Africa.,However, it is difficult to compare the wide array of demographic, socio-economic, and environmental variables associated with malaria transmission using standard statistical approaches while accounting for seasonal differences and nonlinear relationships.,This article uses a Bayesian model averaging (BMA) approach for identifying and comparing potential risk and protective factors associated with residual malaria.,The relative influence of a comprehensive set of demographic, socio-economic, environmental, and malaria intervention variables on malaria prevalence were modelled using BMA for variable selection.,Data were collected in Bunkpurugu-Yunyoo, a rural district in northeast Ghana that experiences holoendemic seasonal malaria transmission, over six biannual surveys from 2010 to 2013.,A total of 10,022 children between the ages 6 to 59 months were used in the analysis.,Multiple models were developed to identify important risk and protective factors, accounting for seasonal patterns and nonlinear relationships.,These models revealed pronounced nonlinear associations between malaria risk and distance from the nearest urban centre and health facility.,Furthermore, the association between malaria risk and age and some ethnic groups was significantly different in the rainy and dry seasons.,BMA outperformed other commonly used regression approaches in out-of-sample predictive ability using a season-to-season validation approach.,This modelling framework offers an alternative approach to disease risk factor analysis that generates interpretable models, can reveal complex, nonlinear relationships, incorporates uncertainty in model selection, and produces accurate predictions.,Certain modelling applications, such as designing targeted local interventions, require more sophisticated statistical methods which are capable of handling a wide range of relevant data while maintaining interpretability and predictive performance, and directly characterize uncertainty.,To this end, BMA represents a valuable tool for constructing more informative models for understanding risk factors for malaria, as well as other vector-borne and environmentally mediated diseases.,The online version of this article (10.1186/s12936-018-2491-2) contains supplementary material, which is available to authorized users.

Asymptomatic individuals are one of the major challenges for malaria elimination programs in endemic areas.,In the absence of clinical symptoms and with a lower parasite density they constitute silent reservoirs considered important for maintaining transmission of human malaria.,Studies from Brazil have shown that infected individuals may carry these parasites for long periods.,Patients were selected from three periurban endemic areas of the city of Manaus, in the western Brazilian Amazon.,Symptomatic and asymptomatic patients with positive thick blood smear and quantitative real-time PCR (qPCR) positive for Plasmodium vivax were invited to participate in the study.,A standardised pvs25 gene amplification by qPCR was used for P. vivax gametocytes detection.,Anopheles aquasalis were fed using membrane feeding assays (MFA) containing blood from malaria patients.,Parasitemia of 42 symptomatic and 25 asymptomatic individuals was determined by microscopic examination of blood smears and qPCR.,Parasitemia density and gametocyte density were assessed as determinants of infection rates and oocysts densities.,A strong correlation between gametocyte densities (microscopy and molecular techniques) and mosquito infectivity (P < 0.001) and oocysts median numbers (P < 0.05) was found in both groups.,The ability to infect mosquitoes was higher in the symptomatic group (41%), but infectivity in the asymptomatic group was also seen (1.42%).,Although their infectivity to mosquitoes is relatively low, given the high prevalence of P. vivax asymptomatic carriers they are likely to play and important role in malaria transmission in the city of Manaus.,The role of asymptomatic infections therefore needs to be considered in future malaria elimination programs in Brazil.,The online version of this article (10.1186/s13071-018-2749-0) contains supplementary material, which is available to authorized users.

Plasmodium vivax and Plasmodium falciparum cause a significant illness burden in Peru.,Anopheline indices for populated communities in the peri-Iquitos region of Loreto have been reported to be remarkably low, with entomological inoculation rates (EIR) estimated at one to 30 infective bites per year based on a few studies in close proximity to the urban centre of Iquitos and surrounding deforested areas.,Local reports suggest that a large number of the reported cases are contracted outside of populated communities in undeveloped riverine areas frequented by loggers and fishermen.,To better understand vectorial capacity in suspected high malaria transmission zones in a rural district near Iquitos, Peru, mosquito collections were conducted at different points in the seasonality of malaria transmission in 21 sites frequented by occupational labourers.,Prevalence of Plasmodium spp in vectors was determined by circumsporozoite protein ELISA on individual mosquitoes.,Slide surveillance was performed for humans encountered in the zone.,In total, of 8,365 adult female mosquitoes examined, 98.5% were identified as Anopheles darlingi and 117 (1.4%) tested positive for sporozoites (P. falciparum, P. vivax VK210 or P. vivax VK247).,Measured human biting rates at these sites ranged from 0.102 to 41.13 bites per person per hour, with EIR values as high as 5.3 infective bites per person per night.,Six percent of the 284 blood films were positive for P. vivax or P. falciparum; however, 88% of the individuals found to be positive were asymptomatic at the time of sampling.,The results of this study provide key missing indices of prominent spatial and temporal heterogeneity of vectorial capacity in the Amazon Basin of Peru.,The identification of a target human subpopulation as a principal reservoir and dispersion source of Plasmodium species has important implications for vaccine development and the delivery of effective targeted malaria control strategies.

Complement is an essential element in both innate and acquired immunity contributing to the immunopathogenesis of many disorders, including Chagas Disease (CD).,Human complement receptor 1 (CR1) plays a role in the clearance of complement opsonized molecules and may facilitate the entry of pathogens into host cells.,Distinct CR1 exon 29 variants have been found associated with CR1 expression levels, increased susceptibility and pathophysiology of several diseases.,In this study, CR1 plasma levels were assessed by ELISA and CR1 variants in exon 29 by sequencing in a Brazilian cohort of 232 chronic CD patients and 104 healthy controls.,CR1 levels were significantly decreased in CD patients compared to controls (p < 0.0001).,The CR1 rs1704660G, rs17047661G and rs6691117G variants were significantly associated with CD and in high linkage disequilibrium.,The CR1*AGAGTG haplotype was associated with T. cruzi infection (p = 0.035, OR 3.99, CI 1.1-14.15) whereas CR1*AGGGTG was related to the risk of chagasic cardiomyopathy (p = 0.028, OR 12.15, CI 1.13-113).,This is the first study that provides insights on the role of CR1 in development and clinical presentation of chronic CD.

Ficolin-2 coded by FCN2 gene is a soluble serum protein that plays an important role in innate immunity.,In this study, we analyzed five functional polymorphisms of the FCN2 gene for their possible association with cutaneous leishmaniasis.,Initially we screened 40 Syrian Arabs for the entire FCN2 gene.,We investigated the contribution of FCN2 functional variants in 226 patients with cutaneous leishmaniasis and 286 healthy controls from Syria.,Polymorphisms in the promoter regions (−986G/A, −602G/A, −4A/G) of the FCN2 gene were assessed by TaqMan real time PCR, whereas polymorphisms in exon8 (+6359C/T and +6424G/T) were assessed by DNA sequencing.,We also measured serum ficolin-2 levels in 70 control Syrian Arabs and correlated the serum concentrations to FCN2 genotypes and haplotypes respectively.,Nine new FCN2 variants including two with non synonymous substitutions in exon6 and exon8 were observed.,The homozygous genotypes +6424T/T were distributed more in controls and none in patients (P = 0.04).,The AGACG haplotype were observed more in patients than in controls (OR = 2.0, 95%CI 1.2-3.4, P = 0.006).,The serum ficolin-2 levels were significantly distributed among the reconstructed ficolin-2 haplotypes (P<0.008) and the haplotype AGACG was observed with higher ficolin-2 levels in 70 control individuals.,Our results demonstrate a significant association of FCN2 AGACG haplotype with cutaneous leishmaniasis in a Syrian Arab population.,These first results provide a basis for a future study that could confirm or disprove possible relationships between FCN2 gene polymorphisms with cutaneous leishmaniasis.

The insecticide-treated mosquito net (ITN) is a crucial component of malaria control programs, and has prevented many malaria cases and deaths due to scale up.,ITNs also serve effectively as fishing nets and various sources have reported use of ITNs for fishing.,This article examines how widespread the practice of mosquito net fishing with ITNs is.,We conducted in-depth interviews with fishery personnel and traditional leadership from the Barotse Royal Establishment in Western Province, Zambia, to better understand the presence or absence of the use of ITNs as fishing nets.,We then coded the interviews for themes through content analysis.,Additionally we conducted a desk review of survey data to show trends in malaria indicators, nutritional status of the population and fish consumption.,All those interviewed reported that ITNs are regularly used for fishing in Western Zambia and the misuse is widespread.,Concurrently those interviewed reported declines in fish catches both in terms of quantity and quality leading to threatened food security in the area.,In addition to unsustainable fishing practices those interviewed referenced drought and population pressure as reasons for fishery decline.,Malaria indicators do not show a trend in declining malaria transmission, fish consumption has dropped dramatically and nutritional status has not improved over time.,Despite the misuse of the ITNs for fishing all those interviewed maintained that ITN distribution should continue.,Donors, control programs and scientists should realize that misuse of ITNs as fishing nets is a current problem for malaria control and potentially for food security that needs to be addressed.

Malaria is a major cause of morbidity and mortality among displaced populations in tropical zones.,Bed nets are widely used to prevent malaria; however, few data are available on bed net distribution within displaced populations.,Mixed methods study in a single internally displaced persons (IDP) camp and neighboring community in Eastern Democratic Republic of the Congo (DRC).,Qualitative data (focus group discussions, FGDs) and quantitative data (door-to-door survey and individual testing using malaria rapid diagnostic test, RDT) were collected.,Ten FGDs were conducted with 55 individuals.,Although malaria was widely recognized as a significant threat and bed nets were freely distributed in the camp, many households did not own or use them.,IDPs converged on the following reasons for low bed net ownership and use: inconvenience of net installation and sale of nets to meet immediate needs such as food.,One hundred households, comprised of 411 individuals, were surveyed in Birambizo.,The burden of malaria was high (45/78 (58%) of children <5 were positive for malaria by RDT) and bed net utilization was low (29/100 (29%) households owned a bed net, and 85/411 (20%) individuals slept under a bed net the previous night).,Children <5 were more likely to use a bed net than older children or adults (OR 3.4 (95%CI 2.0-5.8), p<0.0001).,Compared to 29 bed nets currently in use by study participants, 146 bed nets had been sold (82%) or exchanged (18%) either in the camp (27%) or in the neighbouring village market (73%).,Qualitative descriptions and quantitative analysis revealed pragmatic barriers to bed net usage and widespread sale of freely distributed bed nets within IDP camps, despite a high burden of malaria.,Additional strategies, beyond bed net distribution, are warranted to combat malaria in vulnerable and hard-to-reach population.

Evolution persistently undermines vector control programs through insecticide resistance.,Here we propose a novel strategy which instead exploits evolution to generate and sustain new control tools.,Effective spatial repellents are needed to keep vectors out of houses.,Our approach generates such new repellents by combining a high-toxicity insecticide with a candidate repellent initially effective against only part of the vector population.,By killing mosquitoes that enter treated properties the insecticide selects for vector phenotypes deflected by the repellent, increasing efficacy of the repellent against the target vector population and in turn protecting the insecticide against the spread of insecticide resistance.,Using such evolved spatial repellents offers an evolutionarily sustainable, ‘double-dip’ system of disease control combining mortality and repellence.,We formalize this idea using models which explore vector population genetics and disease transmission probabilities and show that using evolved spatial repellents is theoretically achievable, effective and sustainable.,DOI:http://dx.doi.org/10.7554/eLife.15416.001,Many of the mosquito species that transmit malaria have evolved to bite humans indoors at night, and therefore health programs target them using insecticides sprayed on surfaces inside people’s homes.,This strategy, however, stops working when mosquito populations evolve to resist the insecticide used, either because they are immune to its poisonous effects or because they change their behaviour to avoid it.,Consequently, there is now a need to develop alternative strategies to control mosquitoes that are more sustainable in the face of evolution.,One possibility is repellents that keep mosquitoes out of homes.,Lynch and Boots have now asked whether evolution could be used to create effective repellents from substances that initially repel only part of the mosquito population by pairing them with lethal insecticides sprayed inside people’s homes.,Mathematical models showed that, before insecticide resistance becomes widespread, this “evolved repellence” approach could reduce the spread of malaria by a similar amount to using insecticides alone.,This was particularly true if the models considered that, as well as surviving to give fewer infectious bites, repelled infectious mosquitoes may be less likely to transmit malaria with each feed, for example if they feed more on livestock rather than humans.,The models of Lynch and Boots also show that that the success of the evolved repellence concept in a given location depends on a number of factors.,The proportion of the starting mosquito population that is repelled or resistant can have a large effect.,Similarly, success will also depend on how likely normal, repelled and insecticide-resistant mosquitoes are to reproduce successfully.,These values can be influenced by the choice of insecticide and repellent and how the chemicals are applied.,Lynch and Boots show that swapping insecticides can allow an evolved repellent to be established where it would otherwise not succeed.,Also, the spread of resistance to the paired insecticide is slowed or prevented when the mosquito population evolves to be repelled.,Practical laboratory and field- work is now needed to build on this theoretical groundwork and to determine suitable locations and application strategies to exploit this concept as a way to sustainably reduce the spread of malaria in the future.,DOI:http://dx.doi.org/10.7554/eLife.15416.002

The dramatic success of insecticide treated nets (ITNs) and long-lasting insecticidal nets (LLINs) in African countries has been countered by the rapid development of pyrethroid resistance in vector mosquitoes over the past decade.,One advantage of the use of pyrethroids in ITNs is their excito-repellency.,Use of the excito-repellency of pyrethroids might be biorational, since such repellency will not induce or delay the development of any physiological resistance.,However, little is known about the relationship between the mode of insecticide resistance and excito-repellency in pyrethroid-resistant mosquitoes.,Differences in the reactions of 3 major malaria vectors in western Kenya to pyrethroids were compared in laboratory tests.,Adult susceptibility tests were performed using World Health Organization (WHO) test tube kits for F1 progenies of field-collected An. gambiae s.s., An. arabiensis, and An. funestus s.s., and laboratory colonies of An. gambiae s.s. and An. arabiensis.,The contact repellency to pyrethroids or permethrin-impregnated LLINs (Olyset® Nets) was evaluated with a simple choice test modified by WHO test tubes and with the test modified by the WHO cone bioassay test.,Field-collected An. gambiae s.s., An. arabiensis, and An. funestus s.s. showed high resistance to both permethrin and deltamethrin.,The allelic frequency of the point mutation in the voltage-gated sodium channel (L1014S) in An. gambiae s.s. was 99.3-100%, while no point mutations were detected in the other 2 species.,The frequency of takeoffs from the pyrethroid-treated surface and the flying times without contacting the surface increased significantly in pyrethroid-susceptible An. gambiae s.s. and An. arabiensis colonies and wild An. arabiensis and An. funestus s.s. colonies, while there was no significant increase in the frequency of takeoffs or flying time in the An. gambiae s.s. wild colony.,A different repellent reaction was observed in the field-collected An. gambiae s.s. than in An. arabiensis and An. funestus s.s.,It might be that resistant mosquitoes governed by knockdown resistance (kdr) loose repellency to pyrethroids, whereas those lacking kdr maintain high repellency irrespective of their possessing metabolic resistance factors to pyrethroids.,Further genetic evaluation is required for the demonstration of the above hypothesis.

Lymphatic filariasis, onchocerciasis and loiasis are widespread neglected tropical diseases causing serious public health problems and impacting the socio-economic climate in endemic communities.,More than 100 million people currently suffer from filarial infections but disease-related symptoms and infection-induced immune mechanisms are still ambiguous.,Although most infected individuals have dominant Th2 and regulatory immune responses leading to a homeostatic regulated state, filarial-induced overt pathology like lymphedema, dermal pathologies or blindness can occur.,Interestingly, besides dominant Th2 and regulatory T cell activation, increased Th17-induced immune responses were associated with filarial infection and overt helminth-induced pathology in humans.,However, the immunological mechanisms of Th17 cells and the release of IL-17A during filarial infections remain unclear.,To decipher the role of IL-17A during filarial infection, we naturally infected IL-17A−/− and wildtype C57BL/6 mice with the rodent filariae Litomosoides sigmodontis and analysed parasite development and immune alterations.,Our study reveals that infected IL-17A-deficient C57BL/6 mice present reduced worm burden on days 7 and 28 p.i. but had longer adult worms on day 28 p.i. in the thoracic cavity (TC), the site of infection.,In addition, infiltration of CD4+ T cells, CD4+Foxp3+ regulatory T and functional CD4+Rorγt+pStat3+ Th17 cells in the TC was reduced in IL-17A-deficient mice accompanied by reduced eotaxin-1 and CCL17 levels.,Furthermore, mediastinal lymph node cells isolated from IL-17A−/− mice showed increased filarial-specific IFN-γ but not IL-4, IL-6, or IL-21 secretion.,This study shows that Th17 signalling is important for host immune responses against filarial infection but appears to facilitate worm growth in those that reach the TC.,The online version of this article (10.1007/s00436-018-5959-7) contains supplementary material, which is available to authorized users.

Worldwide more than 2 billion people are infected with helminths, predominantly in developing countries.,Co-infections with viruses such as human immunodeficiency virus (HIV) are common due to the geographical overlap of these pathogens.,Helminth and viral infections induce antagonistic cytokine responses in their hosts.,Helminths shift the immune system to a type 2-dominated immune response, while viral infections skew the cytokine response towards a type 1 immune response.,Moreover, chronic helminth infections are often associated with a generalized suppression of the immune system leading to prolonged parasite survival, and also to a reduced defence against unrelated pathogens.,To test whether helminths affect the outcome of a viral infection we set up a filarial/retrovirus co-infection model in C57BL/6 mice.,Although Friend virus (FV) infection altered the L. sigmodontis-specific immunoglobulin response towards a type I associated IgG2 isotype in co-infected mice, control of L. sigmodontis infection was not affected by a FV-superinfection.,However, reciprocal control of FV infection was clearly impaired by concurrent L. sigmodontis infection.,Spleen weight as an indicator of pathology and viral loads in spleen, lymph nodes (LN) and bone marrow (BM) were increased in L. sigmodontis/FV-co-infected mice compared to only FV-infected mice.,Numbers of FV-specific CD8+ T cells as well as cytokine production by CD4+ and CD8+ cells were alike in co-infected and FV-infected mice.,Increased viral loads in co-infected mice were associated with reduced titres of neutralising FV-specific IgG2b and IgG2c antibodies.,In summary our findings suggest that helminth infection interfered with the control of retroviral infection by dampening the virus-specific neutralising antibody response.

Visceral leishmaniasis (VL) is considered as a major health threat in the Indian subcontinent.,Leishmania donovani, a usually visceralizing species, causes cutaneous leishmaniasis (CL) in Sri Lanka.,However, visceralizing potential of the local L. donovani is not yet fully understood.,This project studied the seroprevalence of local CL by using an in-house ELISA.,An IgG-based ELISA using crude Leishmania antigen (Ag) was developed and validated.,A total of 50 laboratory confirmed cases of locally acquired CL were examined using the newly developed ELISA.,According to the optimized ELISA, seroprevalence of anti-Leishmania IgG antibodies in the study group was 34.0% (n = 17/50).,Majority of seropositive individuals were males (n = 13/17), representing 76%.,Nearly half of the seropositive individuals were young adults (20-40 years, n = 9/17, 53%).,Higher proportions of single lesions, large lesions, and nodular lesions were associated with a seroconversion.,A proportion of local L. donovani infections leading to CL have the ability to raise an antibody response in the host.,This may indicate early systemic involvement as one possibility.,Study of a large number of patients with adequate follow-up would be useful.

To eliminate visceral leishmaniasis (VL) in India and Nepal, challenges of VL diagnosis, treatment and reporting need to be identified.,Recent data indicate that VL is underreported and patients face delays when seeking treatment.,Moreover, VL surveillance data might not reach health authorities on time.,This study quantifies delays for VL diagnosis and treatment, and analyses the duration of VL reporting from district to central health authorities in India and Nepal.,A cross-sectional study conducted in 12 districts of Terai region, Nepal, and 9 districts of Bihar State, India, in 2012.,Patients were interviewed in hospitals or at home using a structured questionnaire, health managers were interviewed at their work place using a semi-structured questionnaire and in-depth interviews were conducted with central level health managers.,Reporting formats were evaluated.,Data was analyzed using two-tailed Mann-Whitney U or Fisher’s exact test.,92 VL patients having experienced 103 VL episodes and 49 district health managers were interviewed.,Patients waited in Nepal 30 days (CI 18-42) before seeking health care, 3.75 times longer than in Bihar (8d; CI 4-12).,Conversely, the lag time from seeking health care to receiving a VL diagnosis was 3.6x longer in Bihar (90d; CI 68-113) compared to Nepal (25d; CI 13-38).,The time span between diagnosis and treatment was short in both countries.,VL reporting time was in Nepal 19 days for sentinel sites and 76 days for “District Public Health Offices (DPHOs)”.,In Bihar it was 28 days for “District Malaria Offices”.,In Nepal, 73% of health managers entered data into computers compared to 16% in Bihar.,In both countries reporting was mainly paper based and standardized formats were rarely used.,To decrease the delay between onset of symptoms and getting a proper diagnosis and treatment the approaches in the two countries vary: In Nepal health education for seeking early treatment are needed while in Bihar the use of private and non-formal practitioners has to be discouraged.,Reinforcement of VL sentinel reporting in Bihar, reorganization of DPHOs in Nepal, introduction of standardized reporting formats and electronic reporting should be conducted in both countries.,The online version of this article (doi:10.1186/s12879-015-0767-5) contains supplementary material, which is available to authorized users.

Artemether-lumefantrine is the most widely used antimalarial artemisinin-based combination treatment.,Recent studies have suggested that day 7 plasma concentrations of the potent metabolite desbutyl-lumefantrine correlate better with treatment outcomes than those of lumefantrine.,Low cure rates have been reported in pregnant women with uncomplicated falciparum malaria treated with artemether-lumefantrine in northwest Thailand.,A simultaneous pharmacokinetic drug-metabolite model was developed based on dense venous and sparse capillary lumefantrine and desbutyl-lumefantrine plasma samples from 116 pregnant patients on the Thailand-Myanmar border.,The best model was used to evaluate therapeutic outcomes with a time-to-event approach.,Lumefantrine and desbutyl-lumefantrine concentrations, implemented in an Emax model, both predicted treatment outcomes, but lumefantrine provided better predictive power.,A combined model including both lumefantrine and desbutyl-lumefantrine did not improve the model further.,Simulations suggested that cure rates in pregnant women with falciparum malaria could be increased by prolonging the treatment course.,(These trials were registered at controlled-trials.com [ISRCTN 86353884].)

Pregnancy alters the pharmacokinetic properties of many drugs used in the treatment of malaria, usually resulting in lower drug exposures.,This increases the risks of treatment failure, adverse outcomes for the fetus, and the development of resistance.,The pharmacokinetic properties of artemether and its principal metabolite dihydroartemisinin (n = 21), quinine (n = 21), and lumefantrine (n = 26) in pregnant Ugandan women were studied.,Lumefantrine pharmacokinetics in a nonpregnant control group (n = 17) were also studied.,Frequently sampled patient data were evaluated with noncompartmental analysis.,No significant correlation was observed between estimated gestational age and artemether, dihydroartemisinin, lumefantrine, or quinine exposures.,Artemether/dihydroartemisinin and quinine exposures were generally low in these pregnant women compared to values reported previously for nonpregnant patients.,Median day 7 lumefantrine concentrations were 488 (range, 30.7 to 3,550) ng/ml in pregnant women compared to 720 (339 to 2,150) ng/ml in nonpregnant women (P = 0.128).,There was no statistical difference in total lumefantrine exposure or maximum concentration.,More studies with appropriate control groups in larger series are needed to characterize the degree to which pregnant women are underdosed with current antimalarial dosing regimens.

The infection status with Clonorchis sinensis metacercariae (CsMc) was examined in freshwater fishes from Yongjeon-cheon (a branch of Nakdong-gang) located in Cheongsong-gun, Gyeongsangbuk-do, the Republic of Korea (Korea).,A total of 750 fishes in 19 species were examined by the artificial digestion method for 2 years (2019 and 2020).,CsMc were detected in 378 (51.4%) out of 735 fishes in 14 species (73.7%), and the infection intensity was 666 per fish infected.,In 2019, CsMc were found in 172 (68.0%) out of 253 fishes in 10 species, and the infection intensity was 565 per fish infected.,In 2020, CsMc were detected in 206 (62.2%) out of 331 fishes in 10 species, and the infection intensity was 751 per fish infected.,The other zoonotic trematode, ie.,Metagonimus spp., Centrocestus armatus, Echinostoma spp. and Clinostomum complanatum, metacercariae were also detected in fishes from the survey streams, but their endemicities were relatively low.,Conclusively, it was first confirmed that CsMc are highly endemic in fishes from Yongjeon-cheon in Cheongsong-gun, Gyeongsangbuk-do, Korea.

We evaluated the status of Clonorchis sinensis infection and potential risk factors among residents of riverside areas (Geumgang) in Muju-gun, Jeollabuk-do (Province), Korea.,From January to February 2010, a total of 349 (171 males, 178 females) stool samples were collected and examined by the formalin-ether concentration technique.,Also, village residents were interviewed using questionnaires to obtain information about C. sinensis infection-related risk factors.,Overall egg-positive rate of C. sinensis was 13.2%.,Egg-positive rates were significantly higher in males, farmers, and residents who had lived there more than 20 years, and in residents who had eaten raw freshwater fish than in opposite groups, respectively.,However, there was no significant difference between age groups, education levels, cigarette smoking, alcohol drinking, health status, past history of infection, and experience of clonorchiasis medication and examination.,Logistic regression analysis was performed to determine risk factors for clonorchiasis.,On univariate analysis, the odds ratios for males, farmers, those who had lived there more than 20 years, and who had eaten raw freshwater fish were 2.41, 4.44, 3.16, and 4.88 times higher than those of the opposites, respectively.,On multivariate analysis, the odds ratio of residents who had eaten raw freshwater fish was 3.2-fold higher than that of those who had not.,These results indicate that residents living in Muju-gun, along the Geum River, Korea, have relatively high C. sinensis egg-positive rates, and the habit of eating raw freshwater fish was the major factor for the maintenance of clonorchiasis.

Microscopic detection of malaria parasites is the standard method for clinical diagnosis of malaria in Brazil.,However, malaria epidemiological surveillance studies specifically aimed at the detection of low-density infection and asymptomatic cases will require more sensitive and field-usable tools.,The diagnostic accuracy of the colorimetric malachite green, loop-mediated, isothermal amplification (MG-LAMP) assay was evaluated in remote health posts in Roraima state, Brazil.,Study participants were prospectively enrolled from health posts (healthcare-seeking patients) and from nearby villages (healthy participants) in three different study sites.,The MG-LAMP assay and microscopy were performed in the health posts.,Two independent readers scored the MG-LAMP tests as positive (blue/green) or negative (clear).,Sensitivity and specificity of local microscopy and MG-LAMP were calculated using results of PET-PCR as a reference.,A total of 91 participants were enrolled.,There was 100% agreement between the two MG-LAMP readers (Kappa = 1).,The overall sensitivity and specificity of MG-LAMP were 90.0% (95% confidence interval (CI) 76.34-97.21%) and 94% (95% CI 83.76-98.77%), respectively.,The sensitivity and specificity of local microscopy were 83% (95% CI 67.22-92.66%) and 100% (95% CI 93.02-100.00%), respectively.,PET-PCR detected six mixed infections (infection with both Plasmodium falciparum and Plasmodium vivax); two of these were also detected by MG-LAMP and one by microscopy.,Microscopy did not detect any Plasmodium infection in the 26 healthy participants; MG-LAMP detected Plasmodium in five of these and PET-PCR assay detected infection in three.,Overall, performing the MG-LAMP in this setting did not present any particular challenges.,MG-LAMP is a sensitive and specific assay that may be useful for the detection of malaria parasites in remote healthcare settings.,These findings suggest that it is possible to implement simple molecular tests in facilities with limited resources.

There is a critical need for developing new malaria diagnostic tools that are sensitive, cost effective and capable of performing large scale diagnosis.,The real-time PCR methods are particularly robust for large scale screening and they can be used in malaria control and elimination programs.,We have designed novel self-quenching photo-induced electron transfer (PET) fluorogenic primers for the detection of P. falciparum and the Plasmodium genus by real-time PCR.,A total of 119 samples consisting of different malaria species and mixed infections were used to test the utility of the novel PET-PCR primers in the diagnosis of clinical samples.,The sensitivity and specificity were calculated using a nested PCR as the gold standard and the novel primer sets demonstrated 100% sensitivity and specificity.,The limits of detection for P. falciparum was shown to be 3.2 parasites/µl using both Plasmodium genus and P. falciparum-specific primers and 5.8 parasites/µl for P. ovale, 3.5 parasites/µl for P. malariae and 5 parasites/µl for P. vivax using the genus specific primer set.,Moreover, the reaction can be duplexed to detect both Plasmodium spp. and P. falciparum in a single reaction.,The PET-PCR assay does not require internal probes or intercalating dyes which makes it convenient to use and less expensive than other real-time PCR diagnostic formats.,Further validation of this technique in the field will help to assess its utility for large scale screening in malaria control and elimination programs.

Malaria is transmitted by many Anopheles species whose proportionate contributions vary across settings.,We re-assessed the roles of Anopheles arabiensis and Anopheles funestus, and examined potential benefits of species-specific interventions in an area in south-eastern Tanzania, where malaria transmission persists, four years after mass distribution of long-lasting insecticide-treated nets (LLINs).,Monthly mosquito sampling was done in randomly selected households in three villages using CDC light traps and back-pack aspirators, between January-2015 and January-2016, four years after the last mass distribution of LLINs in 2011.,Multiplex polymerase chain reaction (PCR) was used to identify members of An. funestus and Anopheles gambiae complexes.,Enzyme-linked immunosorbent assay (ELISA) was used to detect Plasmodium sporozoites in mosquito salivary glands, and to identify sources of mosquito blood meals.,WHO susceptibility assays were done on wild caught female An. funestus s.l, and physiological ages approximated by examining mosquito ovaries for parity.,A total of 20,135 An. arabiensis and 4,759 An. funestus were collected.,The An. funestus group consisted of 76.6% An. funestus s.s, 2.9% An. rivulorum, 7.1% An. leesoni, and 13.4% unamplified samples.,Of all mosquitoes positive for Plasmodium, 82.6% were An. funestus s.s, 14.0% were An. arabiensis and 3.4% were An. rivulorum.,An. funestus and An. arabiensis contributed 86.21% and 13.79% respectively, of annual entomological inoculation rate (EIR).,An. arabiensis fed on humans (73.4%), cattle (22.0%), dogs (3.1%) and chicken (1.5%), but An. funestus fed exclusively on humans.,The An. funestus populations were 100% susceptible to organophosphates, pirimiphos methyl and malathion, but resistant to permethrin (10.5% mortality), deltamethrin (18.7%), lambda-cyhalothrin (18.7%) and DDT (26.2%), and had reduced susceptibility to bendiocarb (95%) and propoxur (90.1%).,Parity rate was higher in An. funestus (65.8%) than An. arabiensis (44.1%).,Though An. arabiensis is still the most abundant vector species here, the remaining malaria transmission is predominantly mediated by An. funestus, possibly due to high insecticide resistance and high survival probabilities.,Interventions that effectively target An. funestus mosquitoes could therefore significantly improve control of persistent malaria transmission in south-eastern Tanzania.

Intensive malaria control interventions in the United Republic of Tanzania have contributed to reductions in malaria prevalence.,Given that malaria control remains reliant upon continued use of long-lasting insecticidal bed nets (LLINs) even when the threat of malaria has been reduced, this qualitative study sought to understand how changes in perceived risk influence LLIN usage, and to explore in more detail the benefits of net use that are unrelated to malaria.,Eleven focus group discussions were conducted in Bukoba Rural district and in Zanzibar Urban West district in late 2011.,Participants were males aged 18 and over, females between the ages of 18 and 49, and females at least 50 years old.,The perceived risk of malaria had decreased among the respondents, and malaria control interventions were credited for the decline.,Participants cited reductions in both the severity of malaria and in their perceived susceptibility to malaria.,However, malaria was still considered a significant threat.,Participants’ conceptualization of risk appeared to be an important consideration for net use.,At the same time, comfort and aspects of comfort (getting a good night’s sleep, avoiding biting pests) appeared to play a large role in personal decisions to use nets consistently or not.,Barriers to comfort (feeling uncomfortable or trapped; perceived difficulty breathing, or itching/rashes) were frequently cited as reasons not to use a net consistently.,While it was apparent that participants acknowledged the malaria-prevention benefits of net use, the exploration of the risk and comfort determinants of net use provides a richer understanding of net use behaviours, particularly in a setting where transmission has fallen and yet consistent net use is still crucial to maintaining those gains.,Future behaviour change communication campaigns should capitalize on the non-malaria benefits of net use that provide a long-term rationale for consistent use even when the immediate threat of malaria transmission has been reduced.

Effective control of tick infestations on dogs is important to reduce the risk of transmission of bacterial, viral, and protozoal pathogens.,Laboratory studies were initiated to determine the efficacy of lotilaner against common ticks infesting dogs in the United States.,Eight studies investigated the efficacy of lotilaner against ticks.,In two studies dogs were infested with both Dermacentor variabilis and Rhipicephalus sanguineus: one additional study was completed for each of these species.,Two studies assessed infestations with Amblyomma americanum and two with Ixodes scapularis.,In all studies, dogs were ranked and blocked by counts from pre-treatment infestations and randomly allocated, at least eight per group, to be treated orally with lotilaner (minimum dose rate 20 mg/kg), or to be untreated controls.,Treatments were administered on Day 0, within 30 min after dogs were fed.,In all studies, infestations were performed with 50 adult ticks on Days -2, 7, 14, 21 and 28, and also on Day 35 for R. sanguineus, D. variabilis and I. scapularis.,Tick counts were completed 48 h after treatment or after each subsequent challenge.,An adequate infestation was defined as at least 25% of the infestation dose recovered from each of at least six control animals at each evaluation.,Efficacy calculations for the primary objective were based on geometric means.,In all studies, lotilaner was 100% effective against existing infestations.,For post-treatment assessments, on only two occasions did efficacy fall below 99%: in one D. variabilis study efficacy was 98.0% on Day 35 and in one I. scapularis study efficacy on Day 16 was 98.4%.,Only mild and transient adverse events were observed, and none were considered to be related to treatment.,Lotilaner was completely effective against existing infestations with four common species of ticks, D. variabilis, R. sanguineus, A. americanum and I. scapularis, that affect dogs in North America, with at least 4 weeks efficacy of 98.0% or more against subsequent challenge infestations.,These results show that lotilaner is a highly effective isoxazoline that offers sustained efficacy against ticks through and beyond the one-month end-of-dose treatment interval.,The online version of this article (10.1186/s13071-017-2476-y) contains supplementary material, which is available to authorized users.

The oral systemic efficacy of lotilaner (Credelio™, Elanco) was evaluated against Demodex spp. in naturally infested dogs with generalized demodicosis.,In this study, 10 dogs with clinical signs of generalized demodicosis and positive for Demodex spp. mites based on skin scrapings were assigned to a single group orally treated with lotilaner (minimum dose of 20 mg/kg) on Days 0, 28 and 56.,For lotilaner-treated dogs, pre-treatment mite counts based on skin scrapings performed at five different sites were reduced by > 99.9% (P < 0.0001) up to 56 days after the first and second monthly doses.,No live mites were detected after Day 56 out to and including Day 84 post-treatment for 100% efficacy of each dog’s Demodex mite infestation.,Nine of 10 dogs were 100% mite-free from Day 28 (first evaluation) through Day 84 (end of study) and live mites were only found once on one dog (Day 56) following treatment with lotilaner.,All dogs in the lotilaner-treated group showed marked improvement in the clinical signs of demodicosis and there were no drug associated adverse events.,A marked improvement in hair re-growth was observed in all the dogs from 6 weeks following initiation of treatment.,In this study lotilaner administered at a minimum oral dose of 20 mg/kg was highly effective in reducing and eliminating live mite counts in dogs with natural infestations of Demodex spp.,The online version of this article (10.1186/s13071-017-2472-2) contains supplementary material, which is available to authorized users.

Malaria intervention in Ethiopia has been strengthened significantly in the past decade.,The Ethiopian government recently stratified the country based upon annual parasite incidence into malaria free, low, moderate and high transmission strata.,Districts with low transmission were targeted for indigenous transmission elimination.,Surveillance on malaria disease incidence is needed for planning control and elimination efforts.,Clinical malaria was monitored prospectively in health facilities in Jimma town, Oromia Region, southwestern Ethiopia from July 2014 to June 2015.,Seasonal cross-sectional parasite prevalence surveys in local communities were conducted in 2014 and 2015 in eight kebeles.,Case report forms were administered to obtain sociodemographic and epidemiological information from patients.,A total of 1434 suspected malaria cases were examined from the health facilities and 428 confirmed malaria cases were found.,Among them, 327 (76.4 %) cases were Plasmodium vivax, 97 (22.7 %) were Plasmodium falciparum, and 4 (0.9 %) were mixed infection of P. vivax and P. falciparum.,The annual malaria incidence rate was 1.7 cases per 1000 people at risk.,Parasite prevalence in the community was less than 3 %.,Household ownership of insecticide-treated nets (ITNs) was 47.3 % (1173/2479) and ITN usage was 37.9 %.,All ITNs were long-lasting insecticidal nets, and repellent use was not found in the study area.,Being male and traveling were the significant risk factors for P. falciparum malaria.,For P. vivax malaria, risk factors included occupation and history of malaria illness during the preceding 30 days.,Epidemiological evidence suggested low clinical malaria incidence and prevalence in Jimma town.,More aggressive measures may be needed to further suppress vivax transmission.,Strategies should be planned targeting sustained control and elimination.,The online version of this article (doi:10.1186/s12936-016-1298-2) contains supplementary material, which is available to authorized users.

The burden of imported malaria is predominantly in travellers visiting friends and relatives (VFR) in sub-Saharan Africa.,The failure of this group to use chemoprophylaxis is recognized as the most important risk factor for the high incidence of disease.,Understanding the reasons for failure to follow national recommendations may relate to knowledge, risk perception, cost, and peer pressure.,Research into these variables is critical to understand and change practices in this group and this study was designed to explore whether knowledge, risk perception and prophylaxis use differs between travellers’ to various destinations and the rest of the UK population.,Two face-to-face questionnaire surveys were conducted to collect information on demographics, malaria knowledge, source, and quality of pre-travel advice, past travel experience and perceived malaria threat.,One was an IPSOS survey of individuals representative of the UK population.,The other was a departure lounge survey (Civil Aviation Authority (CAA)) of passengers departing to malarious regions detailing destinations and use of chemoprophylaxis.,Around a quarter of the 1,991 UK population surveyed had previously travelled to a malarious area.,Five-hundred departing passengers were interviewed, of which 80% travelled for leisure (56% VFR’s) and 42% were travelling to West Africa.,Malaria knowledge among the UK population (score 58.6) was significantly lower than that of individuals who had previously travelled or were travelling (63.8 and 70.7 respectively).,Malaria knowledge was similar in individuals who had and had not sought pre-travel advice and travellers using and not using chemoprophylaxis for their journey.,Leisure travellers to Ghana and Nigeria were predominantly VFRs (74%), whilst 66% of travellers to Kenya were tourists.,Despite similar high knowledge scores and perceived (>90%) threat of the lethality of malaria in the three groups, chemoprophylaxis use in Nigerians (50%) was substantialy lower than in passengers departing to Kenya (78%) and Ghana (82%).,More frequent annual return visits were made to Nigeria (72%) than to Ghana (38%) or Kenya (23%).,Travellers had more malaria knowledge than the non-travelled UK population.,Malaria knowledge, perceived threat, travel experience, and quality of pre-travel advice appear unrelated to the use of chemoprophylaxis in passengers.,Reducing malaria in VFR travellers will require strategies other than improving malaria knowledge and enhancing malaria risk awareness.

Plasmodium vivax is responsible for most of the malaria infections outside Africa and is currently the predominant malaria parasite in countries under elimination programs.,P. vivax preferentially enters young red cells called reticulocytes.,Advances in understanding the molecular and cellular mechanisms of entry are hampered by the inability to grow large numbers of P. vivax parasites in a long‐term in vitro culture.,Recent progress in understanding the biology of the P. vivax Reticulocyte Binding Protein (PvRBPs) family of invasion ligands has led to the identification of a new invasion pathway into reticulocytes, an understanding of their structural architecture and PvRBPs as targets of the protective immune response to P. vivax infection.,This review summarises current knowledge on the role of reticulocytes in P. vivax infection, the function of the PvRBP family of proteins in generating an immune response in human populations, and the characterization of anti‐PvRBP antibodies in blocking parasite invasion.

Plasmodium vivax merozoite invasion is restricted to Duffy positive reticulocytes.,Merozoite interaction with the Duffy antigen is mediated by the P. vivax Duffy binding protein (PvDBP).,The receptor-binding domain of PvDBP maps to an N-terminal cysteine-rich region referred to as region II (PvDBPII).,In addition, a family of P. vivax reticulocyte binding proteins (PvRBPs) mediates interactions with reticulocyte receptors.,The receptor binding domain of P. vivax reticulocyte binding protein 1a (PvRBP1a) maps to a 30 kD region (PvRBP1a30).,Antibodies raised against recombinant PvRBP1a30 and PvDBPII recognize the native P. vivax antigens and inhibit their binding to host receptors.,Rabbit IgG purified from sera raised against PvRBP1a30 and PvDBPII were tested individually and in combination for inhibition of reticulocyte invasion by P. vivax field isolates.,While anti-PvDBPII rabbit IgG inhibits invasion, anti-PvRBP1a30 rabbit IgG does not show significant invasion inhibitory activity.,Combining antibodies against PvDBPII and PvRBP1a30 also does not increase invasion inhibitory activity.,These studies suggest that although PvRBP1a mediates reticulocyte invasion by P. vivax merozoites, it may not be useful to include PvRBP1a30 in a blood stage vaccine for P. vivax malaria.,In contrast, these studies validate PvDBPII as a promising blood stage vaccine candidate for P. vivax malaria.

In India, malaria is a major public health problem in States having predominantly tribal population.,The objective of this analysis was to find out the incidence of malaria in various States/districts having varied proportions of tribal population using National Vector Borne Disease Control Programme (NVBDCP) data.,States and districts were classified into three categories based on proportions of Scheduled Tribes (ST) population as <10, 10-29.9 and 30 per cent + ST population.,Five year average (2008-2012) of all important malaria indicators collected by NVBDCP was taken to normalize the effect of annual fluctuations in malaria incidence.,State level analysis revealed that ten States/UTs with 30 per cent or more tribal population comprising only three per cent of total population, contributed 14 per cent of total malaria, 21 per cent Plasmodium falciparum and 29 per cent of deaths due to malaria.,Similarly, district level analysis showed that districts with 30 per cent or more tribal population comprising about eight per cent country's population contributed to 46 per cent of total malaria cases, 70 per cent P. falciparum and 47 per cent malarial deaths in the country.,Our analysis showed that the neglect of the ethnic communities in tribal areas would be detrimental to the overall reduction of morbidity and mortality due to malaria.,The fight against the increasing burden of malaria in tribal belt requires adoption of multiple approaches and socio-economic development of the tribal communities.

Epidemiological characteristics of clinical malaria may differ from asymptomatic infections, thus both cross-sectional parasite screening and longitudinal clinical case surveillance are necessary for malaria transmission monitoring and control.,In order to monitor malaria transmission, surveillance of clinical malaria from two years of active case surveillance in three cohorts of 6,750 individuals, asymptomatic parasitaemia cases of 5,300 individuals and clinical cases in three study areas were carried out in the western Kenyan highlands in 2009 and 2010.,Age distribution, seasonality and spatial clustering were analysed.,The results revealed a significant difference in the age distribution of clinical cases between passive and active case surveillance, and between clinical case rate and asymptomatic parasite rate.,The number of reported cases from health facilities significantly underestimated clinical malaria incidence.,The increase in asymptomatic parasite prevalence from low to high transmission seasons was significantly higher for infants (<two years) and adults (≥15 years) (500% increase) than that for children (two to 14 years, 65%), but the increase in clinical incidence rates was significantly higher for children (700%) than that for adults (300%).,Hotspot of asymptomatic infections remained unchanged over time, whereas new clusters of clinical malaria cases emerged in the uphill areas during the peak season.,Different surveillance methods revealed different characteristics of malaria infections.,The new transmission hotspots identified during the peak season with only active case surveillance is an important observation with clear implications in the context of malaria elimination.,Both mass parasite screening and active case surveillance are essential for malaria transmission monitoring and control.,The online version of this article (doi:10.1186/s12936-015-0551-4) contains supplementary material, which is available to authorized users.

Cambodia has targeted malaria elimination within its territory by 2025 and is developing a model elimination package of strategies and interventions designed to achieve this goal.,Cambodia adopted a simplified 1-3-7 surveillance model in the Sampov Loun operational health district in western Cambodia beginning in July 2015.,The 1-3-7 approach targets reporting of confirmed cases within one day, investigation of specific cases within three days, and targeted control measures to prevent further transmission within seven days.,In Sampov Loun, response measures included reactive case detection (testing of co-travelers, household contacts and family members, and surrounding households with suspected malaria cases), and provision of health education, and insecticide-treated nets.,Day 28 follow up microscopy was conducted for all confirmed P. falciparum and P. falciparum-mixed-species malaria cases to assess treatment efficacy.,The number of confirmed malaria cases in the district fell from 519 in 2015 to 181 in 2017, and the annual parasite incidence (API) in the district fell from 3.21 per 1000 population to 1.06 per 1000 population.,The last locally transmitted case of malaria in Sampov Loun was identified in March 2016.,In response to the 408 index cases identified, 1377 contacts were screened, resulting in the identification of 14 positive cases.,All positive cases occurred among index case co-travelers.,The experience of the 1-3-7 approach in Sampov Loun indicates that the basic essential malaria elimination package can be feasibly implemented at the operational district level to achieve the goal of malaria elimination in Cambodia and has provided essential information that has led to the refinement of this package.

Border malaria, a shared phenomenon in the Greater Mekong Sub-region of Southeast Asia, is a major obstacle for regional malaria elimination.,Along the China-Myanmar border, an additional problem arose as a result of the settlement of internally displaced people (IDP) in the border region.,Since asymptomatic malaria significantly impacts transmission dynamics, assessment of the prevalence, dynamics and risk factors of asymptomatic malaria infections is necessary.,Cross-sectional surveys were carried out in 3 seasons (March and April, July and November) and 2 sites (villages and IDP camps) in 2015.,A total of 1680 finger-prick blood samples were collected and used for parasite detection by microscopy and nested RT-PCR (nRT-PCR).,Logistic regression models were used to explore the risk factors associated with asymptomatic malaria at individual and household levels.,The prevalence of asymptomatic Plasmodium infections was 23.3% by nRT-PCR, significantly higher than that detected by microscopy (1.5%).,The proportions of Plasmodium vivax, Plasmodium falciparum and mixed-species infections were 89.6, 8.1 and 2.3%, respectively.,Asymptomatic infections showed obvious seasonality with higher prevalence in the rainy season.,Logistic regression analysis identified males and school children (≤ 15 years) as the high-risk populations.,Vector-based interventions, including bed net and indoor residual spray, were found to have significant impacts on asymptomatic Plasmodium infections, with non-users of these measures carrying much higher risks of infection.,In addition, individuals living in poorly constructed households or farther away from clinics were more prone to asymptomatic infections.,Sub-microscopic Plasmodium infections were highly prevalent in the border human populations from IDP camps and surrounding villages.,Both individual- and household-level risk factors were identified, which provides useful information for identifying the high-priority populations to implement targeted malaria control.

Males of the cattle tick Rhipicephalus microplus produce salivary immunoglobulin-binding proteins and allotypic variations in IgG are associated with tick loads in bovines.,These findings indicate that antibody responses may be essential to control tick infestations.,Infestation loads with cattle ticks are heritable: some breeds carry high loads of reproductively successful ticks, in others, few ticks feed and they reproduce inefficiently.,Different patterns of humoral immunity against tick salivary proteins may explain these phenotypes.,We describe the profiles of humoral responses against tick salivary proteins elicited during repeated artificial infestations of bovines of a tick-resistant (Nelore) and a tick-susceptible (Holstein) breed.,We measured serum levels of total IgG1, IgG2 and IgE immunoglobulins and of IgG1 and IgG2 antibodies specific for tick salivary proteins.,With liquid chromatography followed by mass spectrometry we identified tick salivary proteins that were differentially recognized by serum antibodies from tick-resistant and tick-susceptible bovines in immunoblots of tick salivary proteins separated by two-dimensional electrophoresis.,Baseline levels of total IgG1 and IgG2 were significantly higher in tick-susceptible Holsteins compared with resistant Nelores.,Significant increases in levels of total IgG1, but not of IgG2 accompanied successive infestations in both breeds.,Resistant Nelores presented with significantly higher levels of salivary-specific antibodies before and at the first challenge with tick larvae; however, by the third challenge, tick-susceptible Holsteins presented with significantly higher levels of IgG1 and IgG2 tick salivary protein-specific antibodies.,Importantly, sera from tick-resistant Nelores reacted with 39 tick salivary proteins in immunoblots of salivary proteins separated in two dimensions by electrophoresis versus only 21 spots reacting with sera from tick-susceptible Holsteins.,Levels of tick saliva-specific antibodies were not directly correlated with infestation phenotypes.,However, in spite of receiving apparently lower amounts of tick saliva, tick-resistant bovines recognized more tick salivary proteins.,These reactive salivary proteins are putatively involved in several functions of parasitism and blood-feeding.,Our results indicate that neutralization by host antibodies of tick salivary proteins involved in parasitism is essential to control tick infestations.,The online version of this article (doi:10.1186/s13071-017-2077-9) contains supplementary material, which is available to authorized users.

In tropical countries, losses caused by bovine tick Rhipicephalus (Boophilus) microplus infestation have a tremendous economic impact on cattle production systems.,Genetic variation between Bos taurus and Bos indicus to tick resistance and molecular biology tools might allow for the identification of molecular markers linked to resistance traits that could be used as an auxiliary tool in selection programs.,The objective of this work was to identify QTL associated with tick resistance/susceptibility in a bovine F2 population derived from the Gyr (Bos indicus) × Holstein (Bos taurus) cross.,Through a whole genome scan with microsatellite markers, we were able to map six genomic regions associated with bovine tick resistance.,For most QTL, we have found that depending on the tick evaluation season (dry and rainy) different sets of genes could be involved in the resistance mechanism.,We identified dry season specific QTL on BTA 2 and 10, rainy season specific QTL on BTA 5, 11 and 27.,We also found a highly significant genome wide QTL for both dry and rainy seasons in the central region of BTA 23.,The experimental F2 population derived from Gyr × Holstein cross successfully allowed the identification of six highly significant QTL associated with tick resistance in cattle.,QTL located on BTA 23 might be related with the bovine histocompatibility complex.,Further investigation of these QTL will help to isolate candidate genes involved with tick resistance in cattle.

The current World Health Organization (WHO) target for the three major soil-transmitted helminth (STH) infections is to reduce prevalence of moderate-to-heavy infections to below 1% by 2020.,In terms of monitoring and evaluation (M&E), the current WHO guidelines for control of STHs recommend evaluation of infection levels in school-age children (SAC) after five to six years of preventive chemotherapy (PC), using the standard Kato-Katz faecal smear.,Here, we assess the predictive performance of various sampling designs for the evaluation of the morbidity target.,Using two mathematical models for STH transmission and control, we simulate how the number of villages and SAC sampled affect the ability of survey results in sentinel villages to predict the achievement of the morbidity target in PC implementation units (e.g. districts).,As PC is stopped when the prevalence of infection in SAC in sentinel villages is less than 1%, we estimate the positive predictive value (PPV) of this indicator for meeting the morbidity target in the whole district.,The PPV varies by species and PC strategy, and it is generally higher in areas with lower pre-control prevalence.,Sampling a fixed number of SAC spread out over 10 instead of 5 sentinel villages may increase the PPV by up to 20 percentage points.,If every SAC in a village is tested, a higher number of villages may increase the PPV by up to 80 percentage points.,Increasing the proportion of SAC tested per village does not result in a relevant increase of PPV.,Although the WHO guidelines provide a combined strategy to control the three STH species, the efficacy of PC strategies clearly differs by species.,There is added value in considering more villages within implementation units for M&E of morbidity targets, the extent varying by STH species.,A better understanding of pre- and post-control local STH prevalence levels is essential for an adequate M&E strategy including the definition of morbidity targets at the appropriate geographical scale.

Monitoring and evaluation (M&E) programmes are used to collect data which are required to assess the impact of current interventions on their progress towards achieving the World Health Organization (WHO) goals of morbidity control and elimination as a public health problem for schistosomiasis.,Prevalence and intensity of infection data are typically collected from school-aged children (SAC) as they are relatively easy to sample and are thought to be most likely to be infected by schistosome parasites.,However, adults are also likely to be infected.,We use three different age-intensity profiles of infection for Schistosoma mansoni with low, moderate and high burdens of infection in adults to investigate how the age distribution of infection impacts the mathematical model generated recommendations of the preventive chemotherapy coverage levels required to achieve the WHO goals.,We find that for moderate prevalence regions, regardless of the burden of infection in adults, treating SAC only may achieve the WHO goals.,However, for high prevalence regions with a high burden of infection in adults, adult treatment is required to meet the WHO goals.,Hence, we show that the optimal treatment strategy for a defined region requires consideration of the burden of infection in adults as it cannot be based solely on the prevalence of infection in SAC.,Although past epidemiological data have informed mathematical models for the transmission and control of schistosome infections, more accurate and detailed data are required from M&E programmes to accurately determine the optimal treatment strategy for a defined region.,We highlight the importance of collecting prevalence and intensity of infection data from a broader age-range, specifically the inclusion of adult data at baseline (prior to treatment) and throughout the treatment programme if possible, rather than SAC only, to accurately determine the treatment strategy for a defined region.,Furthermore, we discuss additional epidemiological data, such as individual longitudinal adherence to treatment, that should ideally be collected in M&E programmes.

Plasmodium vivax is the main cause of malaria in Nepal.,Relapse patterns have not been characterized previously.,Patients with P. vivax malaria were randomized to receive chloroquine (CQ; 25 mg base/kg given over 3 days) alone or together with primaquine (PQ; 0.25 mg base/kg/day for 14 days) and followed intensively for 1 month, then at 1- to 2-month intervals for 1 year.,Parasite isolates were genotyped.,One hundred and one (49%) patients received CQ and 105 (51%) received CQ + PQ.,In the CQ + PQ arm, there were 3 (4.1%) recurrences in the 73 patients who completed 1 year of follow-up compared with 22 of 78 (28.2%) in the CQ-only arm (risk ratio, 0.146 [95% confidence interval, .046-.467]; P < .0001).,Microsatellite genotyping showed relatively high P. vivax genetic diversity (mean heterozygosity, 0.843 [range 0.570-0.989] with low multiplicity of infection (mean, 1.05) reflecting a low transmission preelimination setting.,Of the 12 genetically homologous relapses, 5 (42%) occurred in a cluster after 9 months, indicating long latency.,Although there may be emerging CQ resistance, the combination of CQ and the standard-dose 14-day PQ regimen is highly efficacious in providing radical cure of short- and long-latency P. vivax malaria in Nepal.,Chloroquine and a standard-dose 14-day primaquine regimen for Plasmodium vivax malaria treatment in Nepal proved to be well tolerated and highly effective in preventing both short- and long-latency relapses.

The emergence and spread of multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion (GMS) threatens global malaria elimination efforts.,Mass drug administration (MDA), the presumptive antimalarial treatment of an entire population to clear the subclinical parasite reservoir, is a strategy to accelerate malaria elimination.,We report a cluster randomised trial to assess the effectiveness of dihydroartemisinin-piperaquine (DP) MDA in reducing falciparum malaria incidence and prevalence in 16 remote village populations in Myanmar, Vietnam, Cambodia, and the Lao People’s Democratic Republic, where artemisinin resistance is prevalent.,After establishing vector control and community-based case management and following intensive community engagement, we used restricted randomisation within village pairs to select 8 villages to receive early DP MDA and 8 villages as controls for 12 months, after which the control villages received deferred DP MDA.,The MDA comprised 3 monthly rounds of 3 daily doses of DP and, except in Cambodia, a single low dose of primaquine.,We conducted exhaustive cross-sectional surveys of the entire population of each village at quarterly intervals using ultrasensitive quantitative PCR to detect Plasmodium infections.,The study was conducted between May 2013 and July 2017.,The investigators randomised 16 villages that had a total of 8,445 residents at the start of the study.,Of these 8,445 residents, 4,135 (49%) residents living in 8 villages, plus an additional 288 newcomers to the villages, were randomised to receive early MDA; 3,790 out of the 4,423 (86%) participated in at least 1 MDA round, and 2,520 out of the 4,423 (57%) participated in all 3 rounds.,The primary outcome, P. falciparum prevalence by month 3 (M3), fell by 92% (from 5.1% [171/3,340] to 0.4% [12/2,828]) in early MDA villages and by 29% (from 7.2% [246/3,405] to 5.1% [155/3,057]) in control villages.,Over the following 9 months, the P. falciparum prevalence increased to 3.3% (96/2,881) in early MDA villages and to 6.1% (128/2,101) in control villages (adjusted incidence rate ratio 0.41 [95% CI 0.20 to 0.84]; p = 0.015).,Individual protection was proportional to the number of completed MDA rounds.,Of 221 participants with subclinical P. falciparum infections who participated in MDA and could be followed up, 207 (94%) cleared their infections, including 9 of 10 with artemisinin- and piperaquine-resistant infections.,The DP MDAs were well tolerated; 6 severe adverse events were detected during the follow-up period, but none was attributable to the intervention.,Added to community-based basic malaria control measures, 3 monthly rounds of DP MDA reduced the incidence and prevalence of falciparum malaria over a 1-year period in areas affected by artemisinin resistance.,P. falciparum infections returned during the follow-up period as the remaining infections spread and malaria was reintroduced from surrounding areas.,Limitations of this study include a relatively small sample of villages, heterogeneity between villages, and mobility of villagers that may have limited the impact of the intervention.,These results suggest that, if used as part of a comprehensive, well-organised, and well-resourced elimination programme, DP MDA can be a useful additional tool to accelerate malaria elimination.,ClinicalTrials.gov NCT01872702,In a cluster-randomized trial, Lorenz von Seidlin & colleagues investigate whether mass drug administration can accelerate malaria elimination in the Greater Mekong Subregion.

Humoral immune responses have the potential to maintain protective antibody levels for years due to the immunoglobulin-secreting activity of long-lived plasma cells (LLPCs).,However, many subunit vaccines under development fail to generate robust LLPC responses, and therefore a variety of strategies are being employed to overcome this limitation, including conjugation to carrier proteins and/or formulation with potent adjuvants.,Pfs25, an antigen expressed on malaria zygotes and ookinetes, is a leading transmission blocking vaccine (TBV) candidate for Plasmodium falciparum.,Currently, the conjugate vaccine Pfs25-EPA/Alhydrogel is in Phase 1 clinical trials in the USA and Africa.,Thus far, it has proven to be safe and immunogenic, but it is expected that a more potent formulation will be required to establish antibody titers that persist for several malaria transmission seasons.,We sought to determine the contribution of carrier determinants and adjuvants in promoting high-titer, long-lived antibody responses against Pfs25.,We found that both adjuvants and carrier proteins influence the magnitude and capacity of Pfs25-specific humoral responses to remain above a protective level.,Furthermore, a liposomal adjuvant with QS21 and a TLR4 agonist (GLA-LSQ) was especially effective at inducing T follicular helper (Tfh) and LLPC responses to Pfs25 when coupled to immunogenic carrier proteins.

There have been significant decreases in malaria mortality and morbidity in the last 10-15 years, and the most advanced pre-erythrocytic malaria vaccine, RTS,S, received a positive opinion from European regulators in July 2015.,However, no blood-stage vaccine has reached a phase III trial.,The first part of this review summarizes the pros and cons of various assays and models that have been and will be used to predict the efficacy of blood-stage vaccines.,In the second part, blood-stage vaccine candidates that showed some efficacy in human clinical trials or controlled human malaria infection models are discussed.,Then, candidates under clinical investigation are described in the third part, and other novel candidates and strategies are reviewed in the last part.

Malaria and HIV co-infection adversely impact the outcome of both diseases and previous studies have mostly focused on falciparum malaria.,Plasmodium vivax contributes to almost half of the malaria cases in India, but the disease burden of HIV and P. vivax co-infection is unclear.,HIV-infected subjects (n=460) were randomly selected from the 4,611 individuals seen at a Voluntary Counseling and Testing Center in Chennai, India between Jan 2 to Dec 31 2008.,Malaria testing was performed on stored plasma samples by nested PCR using both genus-specific and species-specific primers and immunochromatography-based rapid diagnostic test for detecting antibodies against Plasmodium falciparum and P. vivax.,Recent malaria co-infection, defined by the presence of antibodies, was detected in 9.8% (45/460) participants.,Plasmodium vivax accounted for majority of the infections (60%) followed by P. falciparum (27%) and mixed infections (13%).,Individuals with HIV and malaria co-infection were more likely to be men (p=0.01).,Between those with and without malaria, there was no difference in age (p=0.14), CD4+ T-cell counts (p=0.19) or proportion CD4+ T-cell below 200/mL (p=0.51).,Retrospective testing of stored plasma samples for malaria antibodies can facilitate identification of populations with high rates of co-infection, and in this southern India HIV-infected cohort there was a considerable burden of malaria co-infection, predominantly due to P. vivax.,However, the rate of P. falciparum infection was more than 6-fold higher among HIV-infected individuals than what would be expected in the general population in the region.,Interestingly, individuals co-infected with malaria and HIV were not more likely to be immunosuppressed than individuals with HIV infection alone.

Malaria and HIV-1 infection cause significant morbidity and mortality in children in sub-Saharan Africa.,Recurrent malaria infection increases HIV-1 viral load in adults and increases the rate of progression of HIV-1 infection to AIDS.,The effect of malaria on viral loads in children living with AIDS (CLWA) is not clearly known.,One hundred thirty five afebrile HIV-1 positive children having negative blood slides for malaria were recruited at Apac Hospital and followed up for one year.,They were monitored for development of Plasmodium falciparum malaria, which was treated with chloroquine (CQ) + sulfadoxine-pyrimethamine (SP) and the children followed up for 28 days.,HIV-1 viral loads were measured over three time-points: at enrolment (no malaria), during an episode of malaria, and at a visit about 8 weeks (range 6-19 weeks) after the malaria visit when the child had neither parasites nor any intervening malaria episodes (post-malaria).,Primary analyses were restricted to children who on follow up had HIV-1 viral loads measured at the three relevant time-points.,Malaria increased HIV-1 viral load significantly in CLWA.,Low parasitemia (200-4000/Cl) transiently increased viral load by 0.42 log (95% CI 0.29-0.78, p = 0.0002), higher than that reported in adults.,These patients’ viral loads returned to levels similar to those at baseline after treatment.,In 13 patients with high parasitemia (>4000/Cl), the mean increase in viral load was 0.53 log (95% CI 0.14 to 0.51), p<0.0001, remaining significantly higher than at baseline after treatment i.e. mean difference (signed-rank test) in viral load “before” and “after” malaria was significant.,Plasmodium falciparum malaria is associated with increasing HIV-1 viral loads in children, with some viral loads remaining significantly elevated several weeks after antimalarial treatment.,Prolonged post-treatment elevation has important implications for the clinical course in pre-ART HIV-1 positive children and the potential for transmission in sexually active adults.

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

National malaria control programmes and international agencies are keen to scale-up the use of effective rapid diagnostic tests (RDTs) for malaria.,The high proportion of the Ugandan population seeking care at drug shops makes these outlets attractive as providers of malaria RDTs.,However, there is no precedent for blood testing at drug shops and little is known about how such tests might be perceived and used.,Understanding use of drug shops by communities in Uganda is essential to inform the design of interventions to introduce RDTs.,We conducted a qualitative study, with 10 community focus group discussions, and 18 in-depth interviews with drug shop attendants, health workers and district health officials.,The formative study was carried out in Mukono district, central Uganda an area of high malaria endemicity from May-July 2009.,Drug shops were perceived by the community as important in treating malaria and there was awareness among most drug sellers and the community that not all febrile illnesses were malaria.,The idea of introducing RDTs for malaria diagnosis in drug shops was attractive to most respondents.,It was anticipated that RDTs would improve access to effective treatment of malaria, offset high costs associated with poor treatment, and avoid irrational drug use.,However, communities did express fear that drug shops would overprice RDTs, raising the overall treatment cost for malaria.,Other fears included poor adherence to the RDT result, reuse of RDTs leading to infections and fear that RDTs would be used to test for human immune deficiency virus (HIV).,All drug shops visited had no record on patient data and referral of cases to health units was noted to be poor.,These results not only provide useful lessons for implementing the intervention study but have wide implications for scaling up malaria treatment in drug shops.

The continued success of community case management (CCM) programs in low-resource settings depends on the ability of these programs to retain the community health workers (CHWs), many of whom are volunteers, and maintain their high-quality performance.,This study aims to identify factors related to the motivation and satisfaction of CHWs working in a malaria CCM program in two sub-counties in Western Kenya.,We interviewed 70 CHWs who were trained to administer malaria rapid diagnostic tests as part of a broader study evaluating a malaria CCM program.,We identified factors related to CHWs’ motivation and their satisfaction with participation in the program, as well as the feasibility of program scale-up.,We used principal components analysis to develop an overall CHW satisfaction score and assessed associations between this score and individual CHW characteristics as well as their experiences in the program.,The majority of CHWs reported that they were motivated to perform their role in this malaria CCM program by a personal desire to help their community (69%).,The most common challenge CHWs reported was a lack of community understanding about malaria diagnostic testing and CHWs’ role in the program (39%).,Most CHWs (89%) reported that their involvement in the diagnostic testing intervention had either a neutral or a net positive effect on their other CHW activities, including improving skills applicable to other tasks.,CHWs who said they strongly agreed with the statement that their work with the malaria program was appreciated by the community had a 0.76 standard deviation (SD) increase in their overall satisfaction score (95% confidence interval CI = 0.10-1.24, P = 0.03).,Almost all CHWs (99%) strongly agreed that they wanted to continue their role in the malaria program.,Overall, CHWs reported high satisfaction with their role in community-based malaria diagnosis, though they faced challenges primarily related to community understanding and appreciation of the services they provided.,CHWs’ perceptions that the malaria program generally did not interfere with their other activities is encouraging for the sustainability and scale-up of similar CHW programs.

Malaria control intervention coverage increased nationwide in Malawi during 2000-2010.,Trends in intervention coverage were assessed against trends in malaria parasite prevalence, severe anemia (hemoglobin < 8 g/dL), and all-cause mortality in children under 5 years of age (ACCM) using nationally representative household surveys.,Associations between insecticide-treated net (ITN) ownership, malaria morbidity, and ACCM were also assessed.,Household ITN ownership increased from 27.4% (95% confidence interval [CI] = 25.9-29.0) in 2004 to 56.8% (95% CI = 55.6-58.1) in 2010.,Similarly intermittent preventive treatment during pregnancy coverage increased from 28.2% (95% CI = 26.7-29.8) in 2000 to 55.0% (95% CI = 53.4-56.6) in 2010.,Malaria parasite prevalence decreased significantly from 60.5% (95% CI = 53.0-68.0) in 2001 to 20.4% (95% CI = 15.7-25.1) in 2009 in children aged 6-35 months.,Severe anemia prevalence decreased from 20.4% (95% CI: 17.3-24.0) in 2004 to 13.1% (95% CI = 11.0-15.4) in 2010 in children aged 6-23 months.,ACCM decreased 41%, from 188.6 deaths per 1,000 live births (95% CI = 179.1-198.0) during 1996-2000, to 112.1 deaths per 1,000 live births (95% CI = 105.8-118.5) during 2006-2010.,When controlling for other covariates in random effects logistic regression models, household ITN ownership was protective against malaria parasitemia in children (odds ratio [OR] = 0.81, 95% CI = 0.72-0.92) and severe anemia (OR = 0.82, 95% CI = 0.72-0.94).,After considering the magnitude of changes in malaria intervention coverage and nonmalaria factors, and given the contribution of malaria to all-cause mortality in malaria-endemic countries, the substantial increase in malaria control interventions likely improved child survival in Malawi during 2000-2010.

Human angiostrongyliasis (HA) is a neurological helminthic disease caused by the lung worm Angiostrongylus cantonensis.,It is suspected in the combination of travel or a residence in an endemic area and eosinophilic meningitis.,In Mayotte, an island in the Indian Ocean, cases are rare but regular.,The main objective of our study was to describe the epidemiological and diagnosis clues of HA in Mayotte.,The secondary objectives were to evaluate the contribution of Real-Time Polymerase Chain Reaction (RT- PCR) for the diagnosis of HA, delineate the characteristics of the local transmission and ascertain the presence of A. cantonensis in Achatina fulica, the potential vector of the disease.,Between 2007 and 2012, all cases of eosinophilic meningitis were retrospectively included and investigated by RT- PCR in the CSF.,Descriptive analysis was conducted for clinical, biological and radiological features, and were analyzed for all patients together with the search for prognostic factors for mortality.,Concurrently, geolocalization and temporal parameters were studied to correlate the occurrence of the cases with rainfall seasons and snails were collected to enhance a parasitic carriage with real time PCR.,During the 6-year period of the study, 14 cases were identified (2.3 cases/year) and 9 among 10 remaining CSF were positive in PCR.,Among 14 cases of EM, 13 were less than 2 year-old children.,The 1 year mortality rate was 5/14 (35.7%).,Among survivors, 3/7 (42.8%) presented neurological sequelae.,Factors associated with mortality were dysfunction of cranial nerves, abnormal brain imaging, and CSF glucose level inferior to 2 mmol/l.,Occurrence of cases was temporarily and spatially correlated to the rainy season.,Among the 64 collected giant snails, 6 (9.4%) were positive with A. cantonensis PCR.,The likely main route of transmission was the children licking snails, carriers of the parasite.,In Mayotte, HA was mainly found in paediatric cases under 2 years old, and evidenced a life-threatening disease.,PCR seems to be a promising tool in the definitive diagnosis of HA.,Population should be aware of the role of A. fulica, and not let the children have direct contact with the snails.

Angiostrongylus cantonensis and Angiostrongylus mackerrasae are metastrongyloid nematodes that infect various rat species.,Terrestrial and aquatic molluscs are intermediate hosts of these worms while humans and dogs are accidental hosts.,Angiostrongylus cantonensis is the major cause of angiostrongyliasis, a disease characterised by eosinophilic meningitis.,Although both A. cantonensis and A. mackerrasae are found in Australia, A. cantonensis appears to account for most infections in humans and animals.,Due to the occurrence of several severe clinical cases in Sydney and Brisbane, the need for epidemiological studies on angiostrongyliasis in this region has become apparent.,In the present study, a conventional PCR and a TaqMan assay were compared for their ability to amplify Angiostrongylus DNA from DNA extracted from molluscs.,The TaqMan assay was more sensitive, capable of detecting the DNA equivalent to one hundredth of a nematode larva.,Therefore, the TaqMan assay was used to screen molluscs (n=500) of 14 species collected from the Sydney region.,Angiostrongylus DNA was detected in 2 of the 14 mollusc species; Cornu aspersum [14/312 (4.5%)], and Bradybaenia similaris [1/10 (10%)], which are non-native terrestrial snails commonly found in urban habitats.,The prevalence of Angiostrongylus spp. was 3.0% ± 0.8% (CI 95%).,Additionally, experimentally infected Austropeplea lessoni snails shed A. cantonensis larvae in their mucus, implicating mucus as a source of infection.,This is the first Australian study to survey molluscs using real-time PCR and confirms that the garden snail, C. aspersum, is a common intermediate host for Angiostrongylus spp. in Sydney.

Sensitive field-deployable diagnostic tests can assist malaria programs in achieving elimination.,The performance of a new Alere™ Malaria Ag P.f Ultra Sensitive rapid diagnostic test (uRDT) was compared with the currently available SD Bioline Malaria Ag P.f RDT in blood specimens from asymptomatic individuals in Nagongera, Uganda, and in a Karen Village, Myanmar, representative of high- and low-transmission areas, respectively, as well as in pretreatment specimens from study participants from four Plasmodium falciparum-induced blood-stage malaria (IBSM) studies.,A quantitative reverse transcription PCR (qRT-PCR) and a highly sensitive enzyme-linked immunosorbent assay (ELISA) test for histidine-rich protein II (HRP2) were used as reference assays.,The uRDT showed a greater than 10-fold lower limit of detection for HRP2 compared with the RDT.,The sensitivity of the uRDT was 84% and 44% against qRT-PCR in Uganda and Myanmar, respectively, and that of the RDT was 62% and 0% for the same two sites.,The specificities of the uRDT were 92% and 99.8% against qRT-PCR for Uganda and Myanmar, respectively, and 99% and 99.8% against the HRP2 reference ELISA.,The RDT had specificities of 95% and 100% against qRT-PCR for Uganda and Myanmar, respectively, and 96% and 100% against the HRP2 reference ELISA.,The uRDT detected new infections in IBSM study participants 1.5 days sooner than the RDT.,The uRDT has the same workflow as currently available RDTs, but improved performance characteristics to identify asymptomatic malaria infections.,The uRDT may be a useful tool for malaria elimination strategies.

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.

The objectives of this study were to assess the patterns of treatment seeking behaviour for children under five with malaria; and to examine the statistical relationship between out-of-pocket expenditure (OOP) on malaria treatment for under-fives and source of treatment, place of residence, education and wealth characteristics of Uganda households.,OOP expenditure on health care is now a development concern due to its negative effect on households’ ability to finance consumption of other basic needs.,The 2009 Uganda Malaria Indicator Survey was the source of data on treatment seeking behaviour for under-five children with malaria, and patterns and levels of OOP expenditure for malaria treatment.,Binomial logit and Log-lin regression models were estimated.,In logit model the dependent variable was a dummy (1=incurred some OOP, 0=none incurred) and independent variables were wealth quintiles, rural versus urban, place of treatment, education level, sub-region, and normal duty disruption.,The dependent variable in Log-lin model was natural logarithm of OOP and the independent variables were the same as mentioned above.,Five key descriptive analysis findings emerge.,First, malaria is quite prevalent at 44.7% among children below the age of five.,Second, a significant proportion seeks treatment (81.8%).,Third, private providers are the preferred option for the under-fives for the treatment of malaria.,Fourth, the majority pay about 70.9% for either consultation, medicines, transport or hospitalization but the biggest percent of those who pay, do so for medicines (54.0%).,Fifth, hospitalization is the most expensive at an average expenditure of US$7.6 per child, even though only 2.9% of those that seek treatment are hospitalized.,The binomial logit model slope coefficients for the variables richest wealth quintile, Private facility as first source of treatment, and sub-regions Central 2, East central, Mid-eastern, Mid-western, and Normal duties disrupted were positive and statistically significant at 99% level of confidence.,On the other hand, the Log-lin model slope coefficients for Traditional healer, Sought treatment from one source, Primary educational level, North East, Mid Northern and West Nile variables had a negative sign and were statistically significant at 95% level of confidence.,The fact that OOP expenditure is still prevalent and private provider is the preferred choice, increasing public provision may not be the sole answer.,Plans to improve malaria treatment should explicitly incorporate efforts to protect households from high OOP expenditures.,This calls for provision of subsidies to enable the private sector to reduce prices, regulation of prices of malaria medicines, and reduction/removal of import duties on such medicines.

Access to prompt and effective treatment is a cornerstone of the current malaria control strategy.,Delays in starting appropriate treatment is a major contributor to malaria mortality.,WHO recommends home management of malaria using artemisininbased combination therapy (ACT) and Rapid Diagnostic tests (RDTs) as one of the strategies for improving access to prompt and efective malaria case management.,A prospective evaluation of the effectiveness of using community health workers (CHWs) as delivery points for ACT and RDTs in the home management of malaria in two districts in Zambia.,CHWs were able to manage malaria fevers by correctly interpreting RDT results and appropriately prescribing antimalarials.,All severe malaria cases and febrile non-malaria fevers were referred to a health facility for further management.,There were variations in malaria prevalence between the two districts and among the villages in each district. 100% and 99.4% of the patients with a negative RDT result were not prescribed an antimalarial in the two districts respectively.,No cases progressed to severe malaria and no deaths were recorded during the study period.,Community perceptions were positive.,CHWs are effective delivery points for prompt and effective malaria case management at community level.,Adherence to test results is the best ever reported in Zambia.,Further areas of implementation research are discussed.

The aim of this study is to describe the major evolutionary historical events among Leishmania, sandflies, and the associated animal reservoirs in detail, in accordance with the geographical evolution of the Earth, which has not been previously discussed on a large scale.,Leishmania and sandfly classification has always been a controversial matter, and the increasing number of species currently described further complicates this issue.,Despite several hypotheses on the origin, evolution, and distribution of Leishmania and sandflies in the Old and New World, no consistent agreement exists regarding dissemination of the actors that play roles in leishmaniasis.,For this purpose, we present here three centuries of research on sandflies and Leishmania descriptions, as well as a complete description of Leishmania and sandfly fossils and the emergence date of each Leishmania and sandfly group during different geographical periods, from 550 million years ago until now.,We discuss critically the different approaches that were used for Leishmana and sandfly classification and their synonymies, proposing an updated classification for each species of Leishmania and sandfly.,We update information on the current distribution and dispersion of different species of Leishmania (53), sandflies (more than 800 at genus or subgenus level), and animal reservoirs in each of the following geographical ecozones: Palearctic, Nearctic, Neotropic, Afrotropical, Oriental, Malagasy, and Australian.,We propose an updated list of the potential and proven sandfly vectors for each Leishmania species in the Old and New World.,Finally, we address a classical question about digenetic Leishmania evolution: which was the first host, a vertebrate or an invertebrate?,We propose an updated view of events that have played important roles in the geographical dispersion of sandflies, in relation to both the Leishmania species they transmit and the animal reservoirs of the parasites.

Cutaneous leishmaniasis (CL) is a neglected clinical form of public health importance that is quite prevalent in the northern and eastern parts of Egypt.,A comprehensive study over seven years (January 2005-December 2011) was conducted to track CL transmission with respect to both sandfly vectors and animal reservoirs.,The study identified six sandfly species collected from different districts in North Sinai: Phlebotomus papatasi, Phlebotomus kazeruni, Phlebotomus sergenti, Phlebotomus alexandri, Sergentomyia antennata and Sergentomyia clydei.,Leishmania (-)-like flagellates were identified in 15 P. papatasi individuals (0.5% of 3,008 dissected females).,Rodent populations were sampled in the same districts where sandflies were collected and eight species were identified: Rattus norvegicus (n = 39), Rattus rattus frugivorous (n = 13), Rattus rattus alexandrinus (n = 4), Gerbillus pyramidum floweri (n = 38), Gerbillus andersoni (n = 28), Mus musculus (n = 5), Meriones sacramenti (n = 22) and Meriones crassus (n = 10).,Thirty-two rodents were found to be positive for Leishmania infection (20.12% of 159 examined rodents).,Only Leishmania major was isolated and identified in 100% of the parasite samples.,The diversity of both the vector and rodent populations was examined using diversity indices and clustering approaches.

BG-Malaria (BGM) trap is a simple adaptation of the widely-used BG-Sentinel trap (BGS).,It is proven to be highly effective for trapping the Brazilian malaria vector, Anopheles darlingi, in field conditions, and the African vector, Anopheles arabiensis, under controlled semi-field environments, but has not been field-tested in Africa.,Here, we validated the BGM for field sampling of malaria vectors in south-eastern Tanzania.,Using a series of Latin-Square experiments conducted nightly (6pm-7am) in rural villages, we compared mosquito catches between BGM, BGS and human landing catches (HLC).,We also compared BGMs baited with different attractants (Ifakara-blend, Mbita-blend, BG-Lure and CO2).,Lastly, we tested BGMs baited with Ifakara-blend from three odour-dispensing methods (BG-Cartridge, BG-Sachet and Nylon strips).,One-tenth of the field-collected female Anopheles gambiae s.l. and Anopheles funestus were dissected to assess parity.,BGM captured more An. gambiae s.l. than BGS (p < 0.001), but HLC caught more than either trap (p < 0.001).,However, BGM captured more An. funestus than HLC.,Proportions of parous An. gambiae s.l. and An. funestus consistently exceeded 50%, with no significant difference between methods.,While the dominant species caught by HLC was An. gambiae s.l.,(56.0%), followed by Culex spp.,(33.1%) and Mansonia spp.,(6.0%), the BGM caught mostly Culex (81.6%), followed by An. gambiae s.l.,(10.6%) and Mansonia (5.8%).,The attractant-baited BGMs were all significantly superior to un-baited controls (p < 0.001), although no difference was found between the specific attractants.,The BG-Sachet was the most efficient dispenser for capturing An. gambiae s.l.,(14.5(2.75-42.50) mosquitoes/trap/night), followed by BG-Cartridge (7.5(1.75-26.25)).,The BGM caught more mosquitoes than BGS in field-settings, but sampled similar species diversity and physiological states as BGS.,The physiological states of malaria vectors caught in BGM and BGS were similar to those naturally attempting to bite humans (HLC).,The BGM was most efficient when baited with Ifakara blend, dispensed from BG-Sachet.,We conclude that though BGM traps have potential for field-sampling of host-seeking African malaria vectors with representative physiological states, both BGM and BGS predominantly caught more culicines than Anopheles, compared to HLC, which caught mostly An. gambiae s.l.

Distribution, abundance, feeding behaviour, host preference, parity status and human-biting and infection rates are among the medical entomological parameters evaluated when determining the vector capacity of mosquito species.,To evaluate these parameters, mosquitoes must be collected using an appropriate method.,Malaria is primarily transmitted by anthropophilic and synanthropic anophelines.,Thus, collection methods must result in the identification of the anthropophilic species and efficiently evaluate the parameters involved in malaria transmission dynamics.,Consequently, human landing catches would be the most appropriate method if not for their inherent risk.,The choice of alternative anopheline collection methods, such as traps, must consider their effectiveness in reproducing the efficiency of human attraction.,Collection methods lure mosquitoes by using a mixture of olfactory, visual and thermal cues.,Here, we reviewed, classified and compared the efficiency of anopheline collection methods, with an emphasis on Neotropical anthropophilic species, especially Anopheles darlingi, in distinct malaria epidemiological conditions in Brazil.

In the absence of microscopy, Plasmodium falciparum histidine-rich proteins 2 (PfHRP2)-based rapid diagnostic tests (RDTs) are recommended for the diagnosis of falciparum malaria, particularly in endemic regions.,However, genetic variability of the pfhrp2 gene threatens the usefulness of the test due to its impact on RDT sensitivity.,This study aimed to investigate the diversity of pfhrp2 in malaria cases among children in Ghana.,A cross-sectional study was conducted at the Adidome Government Hospital in the Volta Region of Ghana.,A total of 50 children with mean age of 6.6 ± 3.5 years and diagnosed falciparum malaria were included.,Blood samples were collected for complete blood count, malaria parasite identification and counting using auto analyzer and microscopy, respectively.,DNA was isolated from blood-spotted Whatman filters, amplified and sequenced.,Nucleotide sequences were translated in silico to corresponding amino acids and the deduced amino acids sequences were analyzed for diversity using Mega X.,The number of repeats and number of each repeat within PfHRP2 varied between isolates.,Twelve rare PfHRP2 repeat types, two of which are previously unreported, were identified in this study.,The HRP2 sequence obtained in this study shared high similarities with isolates from Kenya.,Using Baker’s regression model, Group B was the highest occurring type (58.0%).,Screening of all sequences for epitopes recognized by PfHRP2-specific monoclonal antibodies (mAbs), the predominant motif was AHHAADAHH, which is recognized by the C1-13 mAbs.,This study reports diversity of P. falciparum HRP2 in samples from Ghanaian children with symptomatic malaria.,The findings of this study highlight the existence of extra amino acid repeat types which adds to the PfHRP2 antigenic variability.

Malaria rapid diagnostic tests (RDTs) play a critical role in malaria case management, surveillance and case investigations.,Test performance is largely determined by design and quality characteristics, such as detection sensitivity, specificity, and thermal stability.,However, parasite characteristics such as variable or absent expression of antigens targeted by RDTs can also affect RDT performance.,Plasmodium falciparum parasites lacking the PfHRP2 protein, the most common target antigen for detection of P. falciparum, have been reported in some regions.,Therefore, accurately mapping the presence and prevalence of P. falciparum parasites lacking pfhrp2 would be an important step so that RDTs targeting alternative antigens, or microscopy, can be preferentially selected for use in such regions.,Herein the available evidence and molecular basis for identifying malaria parasites lacking PfHRP2 is reviewed, and a set of recommended procedures to apply for future investigations for parasites lacking PfHRP2, is proposed.

In malaria endemic countries of sub-Saharan Africa, many children develop severe anaemia due to previous and current malaria infections.,After blood transfusions and antimalarial treatment at the hospital they are usually discharged without any follow-up.,In the post-discharge period, these children may contract new malaria infections and develop rebound severe anaemia.,A randomised placebo-controlled trial in Malawi showed 31% reduction in malaria- and anaemia-related deaths or hospital readmissions among children under 5 years of age given antimalarial drugs for 3 months post-discharge.,Thus, post-discharge malaria chemoprevention (PMC) may provide substantial protection against malaria and anaemia in young children living in areas of high malaria transmission.,A delivery implementation trial is currently being conducted in Malawi to determine the optimal strategy for PMC delivery.,In the trial, PMC is delivered through community- or facility-based methods with or without the use of reminders via phone text message or visit from a Health Surveillance Assistant.,This paper describes the acceptance of PMC among caregivers.,From October to December 2016, 30 in-depth interviews and 5 focus group discussions were conducted with caregivers of children who recently completed the last treatment course in the trial.,Views on the feasibility of various delivery methods and reminder strategies were collected.,The interviews were transcribed verbatim, translated to English, and coded using the software programme NVivo.,Community-based delivery was perceived as more favourable than facility-based delivery due to easy home access to drugs and fewer financial concerns.,Many caregivers reported lack of visits from Health Surveillance Assistants and preferred text message reminders sent directly to their phones rather than waiting on these visits.,Positive attitudes towards active use of health cards for remembering treatment dates were especially evident.,Additionally, caregivers shared positive experiences from participation in the programme and described dihydroartemisinin-piperaquine as a safe and effective antimalarial drug that improved the health and well-being of their children.,Post-discharge malaria chemoprevention given to children under the age of 5 previously treated for severe anaemia is highly accepted among caregivers.,Caregivers prefer community-based delivery with use of health cards as their primary tool of reference.,NCT02721420 (February 13, 2016).

Intermittent preventive treatment of malaria in children (IPTc) involves the administration of a course of anti-malarial drugs at specified time intervals to children at risk of malaria regardless of whether or not they are known to be infected.,IPTc provides a high level of protection against uncomplicated and severe malaria, with monthly sulphadoxine-pyrimethamine plus amodiaquine (SP&AQ) and sulphadoxine-pyrimethamine plus piperaquine being the most efficacious regimens.,A key challenge is the identification of a cost-effective delivery strategy.,A community randomized trial was undertaken in Jasikan district, Ghana to assess IPTc effectiveness and costs using SP&AQ delivered in three different ways.,Twelve villages were randomly selected to receive IPTc from village health workers (VHWs) or facility-based nurses working at health centres' outpatient departments (OPD) or EPI outreach clinics.,Children aged 3 to 59 months-old received one IPT course (three doses) in May, June, September and October.,Effectiveness was measured in terms of children covered and adherent to a course and delivery costs were calculated in financial and economic terms using an ingredient approach from the provider perspective.,The economic cost per child receiving at least the first dose of all 4 courses was US$4.58 when IPTc was delivered by VHWs, US$4.93 by OPD nurses and US$ 5.65 by EPI nurses.,The unit economic cost of receiving all 3 doses of all 4 courses was US$7.56 and US$8.51 when IPTc was delivered by VHWs or facility-based nurses respectively.,The main cost driver for the VHW delivery was supervision, reflecting resources used for travelling to more remote communities rather than more intense supervision, and for OPD and EPI delivery, it was the opportunity cost of the time spent by nurses in dispensing IPTc.,VHWs achieve higher IPTc coverage and adherence at lower costs than facility-based nurses in Jasikan district, Ghana.,ClinicalTrials.gov NCT00119132.

The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses.,Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite - MSP1 and AMA1.,These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors - ChAd63 to prime the immune response and MVA to boost.,In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI) with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia.,Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i) ChAd63-MVA immunization, ii) immunization and CHMI, and iii) primary malaria exposure in the context of CHMI in unimmunized control volunteers.,Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure.,Serum antibody responses against MSP1 and AMA1 were characterized in terms of i) total IgG responses before and after CHMI, ii) responses to allelic variants of MSP1 and AMA1, iii) functional growth inhibitory activity (GIA), iv) IgG avidity, and v) isotype responses (IgG1-4, IgA and IgM).,These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure.,Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite.,Given the continued clinical development of viral vectored vaccines for malaria and a range of other diseases targets, these data should help to guide further immuno-monitoring studies of vaccine-induced human antibody responses.

Subtelomeric multigene families of malaria parasites encode virulent determinants.,The published genome sequence of Plasmodium vivax revealed the largest subtelomeric multigene family of human malaria parasites, the vir super-family, presently composed of 346 vir genes subdivided into 12 different subfamilies based on sequence homologies detected by BLAST.,A novel computational approach was used to redefine vir genes.,First, a protein-weighted graph was built based on BLAST alignments.,This graph was processed to ensure that edge weights are not exclusively based on the BLAST score between the two corresponding proteins, but strongly dependant on their graph neighbours and their associations.,Then the Markov Clustering Algorithm was applied to the protein graph.,Next, the Homology Block concept was used to further validate this clustering approach.,Finally, proteome-wide analysis was carried out to predict new VIR members.,Results showed that (i) three previous subfamilies cannot longer be classified as vir genes; (ii) most previously unclustered vir genes were clustered into vir subfamilies; (iii) 39 hypothetical proteins were predicted as VIR proteins; (iv) many of these findings are supported by a number of structural and functional evidences, sub-cellular localization studies, gene expression analysis and chromosome localization (v) this approach can be used to study other multigene families in malaria.,This methodology, resource and new classification of vir genes will contribute to a new structural framing of this multigene family and other multigene families of malaria parasites, facilitating the design of experiments to understand their role in pathology, which in turn may help furthering vaccine development.

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

Insecticide treatment of nets, curtains or walls and ceilings of houses represent the primary means for malaria prevention worldwide.,Direct personal protection of individuals and households arises from deterrent and insecticidal activities which divert or kill mosquitoes before they can feed.,However, at high coverage, community-level reductions of mosquito density and survival prevent more transmission exposure than the personal protection acquired by using a net or living in a sprayed house.,A process-explicit simulation of malaria transmission was applied to results of 4 recent Phase II experimental hut trials comparing a new mosaic long-lasting insecticidal net (LLIN) which combines deltamethrin and piperonyl butoxide with another LLIN product by the same manufacturer relying on deltamethrin alone.,Direct estimates of mean personal protection against insecticide-resistant vectors in Vietnam, Cameroon, Burkina Faso and Benin revealed no clear advantage for combination LLINs over deltamethrin-only LLINs (P = 0.973) unless both types of nets were extensively washed (Relative mean entomologic inoculation rate (EIR) ± standard error of the mean (SEM) for users of combination nets compared to users of deltamethrin only nets = 0.853 ± 0.056, P = 0.008).,However, simulations of impact at high coverage (80% use) predicted consistently better impact for the combination net across all four sites (Relative mean EIR ± SEM in communities with combination nets, compared with those using deltamethrin only nets = 0.613 ± 0.076, P < 0.001), regardless of whether the nets were washed or not (P = 0.467).,Nevertheless, the degree of advantage obtained with the combination varied substantially between sites and their associated resistant vector populations.,Process-explicit simulations of community-level protection, parameterized using locally-relevant experimental hut studies, should be explicitly considered when choosing vector control products for large-scale epidemiological trials or public health programme procurement, particularly as growing insecticide resistance necessitates the use of multiple active ingredients.

Sleeping under insecticide-treated mosquito nets/long-lasting insecticidal nets (ITNs/LLINs henceforth referred to as ITNs) is one of the core interventions recommended by the World Health Organization to reduce malaria transmission and prevent malaria in high-risk communities, such as migrants, by preventing mosquito bites.,The malaria burden among the migrant population is a big challenge for malaria elimination in Myanmar.,In this context, this study aimed to assess the ownership and utilization of ITNs and to understand the barriers to distribution and utilization of ITNs among the high-risk migrant communities in the Regional Artemisinin Resistance Initiative (RAI) project areas of Myanmar.,A sequential mixed methods study (quantitative component: cross-sectional study involving analysis of secondary data available from a survey conducted among migrant households in the RAI project areas of Myanmar in 2016 followed by a descriptive qualitative component in 2018).,A total of 17 focus group discussions (involving 121 participants) with different groups of migrants and 17 key-informant interviews with key programme stakeholders were conducted in 4 selected townships of RAI project areas.,Of 3230 migrant households, 63.3% had at least one ITN while 36% had sufficient ITNs (i.e., 1 ITN per 2 persons).,Regarding ITN utilization, about 52% of household members reported sleeping under an ITN the previous night, which is similar among under-fives and pregnant women.,Over half of all bed nets were ITNs, with nearly one-third having holes or already undergone repairs.,The qualitative findings revealed that the key challenges for ITN utilization were insufficient ITNs in households and dislike of ITNs.,The barriers to ITN distribution were incomplete migrant mapping due to resource constraints (time, money, manpower) and difficulties in transportation and carrying ITNs.,This study highlights poor ownership and utilization of ITNs among migrants in the RAI project areas of Myanmar and barriers to their ownership and utilization.,To achieve universal coverage and utilization, more programmatic support by the programme is needed to carry out complete migrant mapping and continuous ITN distribution in remote locations.

Brazil currently contributes 42 % of all malaria cases reported in the Latin America and the Caribbean, a region where major progress towards malaria elimination has been achieved in recent years.,In 2014, malaria burden in Brazil (143,910 microscopically confirmed cases and 41 malaria-related deaths) has reached its lowest levels in 35 years, Plasmodium falciparum is highly focal, and the geographic boundary of transmission has considerably shrunk.,Transmission in Brazil remains entrenched in the Amazon Basin, which accounts for 99.5 % of the country’s malaria burden.,This paper reviews major lessons learned from past and current malaria control policies in Brazil.,A comprehensive discussion of the scientific and logistic challenges that may impact malaria elimination efforts in the country is presented in light of the launching of the Plan for Elimination of Malaria in Brazil in November 2015.,Challenges for malaria elimination addressed include the high prevalence of symptomless and submicroscopic infections, emerging anti-malarial drug resistance in P. falciparum and Plasmodium vivax and the lack of safe anti-relapse drugs, the largely neglected burden of malaria in pregnancy, the need for better vector control strategies where Anopheles mosquitoes present a highly variable biting behaviour, human movement, the need for effective surveillance and tools to identify foci of infection in areas with low transmission, and the effects of environmental changes and climatic variability in transmission.,Control actions launched in Brazil and results to come are likely to influence control programs in other countries in the Americas.

Background: Anisakiasis is a zoonotic disease caused by accidental ingestion of live Anisakis spp. third-stage larvae present in raw or undercooked seafood.,Symptoms of this emerging infectious disease include mild-to-severe abdominal pain, nausea, and diarrhea.,Some patients experience significant allergic reactions.,Aims: In order to better understand the onset of anisakiasis, we aimed to: (i) histopathologically describe severe inflammatory/hemorrhagic infection site lesions in Sprague-Dawley rats experimentally infected with Anisakis pegreffii larvae; and (ii) qualitatively and quantitatively characterize the transcriptomes of affected tissues using RNA-Seq.,Methodology: The experiment was performed on 35 male rats, sacrificed at 5 time points (6, 10, 18, 24, and 32 h post-infection).,Gastric intubation was performed with 10 A. pegreffii larvae (N = 5 infected rats per time point) or 1.5 ml of saline (external control N = 2 rats). 16 pools, seven for muscle tissues and nine for stomach tissues, were created to obtain robust samples for estimation of gene expression changes depicting common signatures of affected versus unaffected tissues.,Illumina NextSeq 500 was used for paired-end sequencing, while edgeR was used for count data and differential expression analyses.,Results: In total, there were 1372 (855 up and 517 down) differentially expressed (DE) genes in the Anisakis-infected rat stomach tissues, and 1633 (1230 up and 403 down) DE genes in the muscle tissues.,Elicited strong local proinflammatory reaction seems to favor the activation of the interleukin 17 signaling pathway and the development of the T helper 17-type response.,The number of DE ribosomal genes in the Anisakis-infected stomach tissue suggests that A. pegreffii larvae might induce ribosomal stress in the early infection stage.,However, the downstream pathways and post-infection responses require further study.,Histopathology revealed severe inflammatory/hemorrhagic lesions caused by Anisakis infection in the rat stomach and muscle tissues in the first 32 h.,The lesion sites showed infiltration by polymorphonuclear leukocytes (predominantly neutrophils and occasional eosinophils), and to a lesser extent, macrophages.,Conclusion: Understanding the cellular and molecular mechanisms underlying host responses to Anisakis infection is important to elucidate many aspects of the onset of anisakiasis, a disease of growing public health concern.

Larval stages of the sibling species of parasitic nematodes Anisakis simplex (sensu stricto) (s.s.),(AS) and Anisakis pegreffii (AP) are responsible for a fish-borne zoonosis, known as anisakiasis, that humans aquire via the ingestion of raw or undercooked infected fish or fish-based products.,These two species differ in geographical distribution, genetic background and peculiar traits involved in pathogenicity.,However, thus far little is known of key molecules potentially involved in host-parasite interactions.,Here, high-throughput RNA-Seq and bioinformatics analyses of sequence data were applied to the characterization of the whole sets of transcripts expressed by infective larvae of AS and AP, as well as of their pharyngeal tissues, in a bid to identify transcripts potentially involved in tissue invasion and host-pathogen interplay.,Approximately 34,000,000 single-end reads were generated from cDNA libraries for each species.,Transcripts identified in AS and AP encoded 19,403 and 10,424 putative peptides, respectively, and were classified based on homology searches, protein motifs, gene ontology and biological pathway mapping.,Differential gene expression analysis yielded 226 and 339 transcripts upregulated in the pharyngeal regions of AS and AP, respectively, compared with their corresponding whole-larvae datasets.,These included proteolytic enzymes, molecules encoding anesthetics, inhibitors of primary hemostasis and virulence factors, anticoagulants and immunomodulatory peptides.,This work provides the scientific community with a list of key transcripts expressed by AS and AP pharyngeal tissues and corresponding annotation information which represents a ready-to-use resource for future functional studies of biological pathways specifically involved in host-parasite interplay.,The online version of this article (10.1186/s13071-017-2585-7) contains supplementary material, which is available to authorized users.

Background.,Current malaria diagnostic tests, including microscopy and antigen-detecting rapid tests, cannot reliably detect low-density infections.,Molecular methods such as polymerase chain reaction (PCR) are highly sensitive but remain too complex for field deployment.,A new commercial molecular assay based on loop-mediated isothermal amplification (LAMP) was assessed for field use.,Methods.,Malaria LAMP (Eiken Chemical, Japan) was evaluated for samples from 272 outpatients at a rural Ugandan clinic and compared with expert microscopy, nested PCR, and quantitative PCR (qPCR).,Two technicians performed the assay after 3 days of training, using 2 alternative blood sample-preparation methods and visual interpretation of results by fluorescence assay.,Results.,Compared with 3-well nested PCR, the sensitivity of both LAMP and single-well nested PCR was 90%; the microscopy sensitivity was 51%.,For samples with a Plasmodium falciparum qPCR titer of ≥2 parasites/µL, LAMP sensitivity was 97.8% (95% confidence interval, 93.7%-99.5%).,Most false-negative LAMP results involved samples with parasitemia levels detectable by 3-well nested PCR but very low or undetectable by qPCR.,Conclusions.,Malaria LAMP in a remote Ugandan clinic achieved sensitivity similar to that of single-well nested PCR in a United Kingdom reference laboratory.,LAMP dramatically lowers the detection threshold achievable in malaria-endemic settings, providing a new tool for diagnosis, surveillance, and screening in elimination strategies.

Diagnostic tests are recommended for suspected malaria cases before treatment, but comparative performance of microscopy and rapid diagnostic tests (RDTs) at rural health centers has rarely been studied compared to independent expert microscopy.,Participants (N = 1997) with presumptive malaria were recruited from ten health centers with a range of transmission intensities in Amhara Regional State, Northwest Ethiopia during October to December 2007.,Microscopy and ParaScreen Pan/Pf® RDT were done immediately by health center technicians.,Blood slides were re-examined later at a central laboratory by independent expert microscopists.,Of 1,997 febrile patients, 475 (23.8%) were positive by expert microscopists, with 57.7% P.falciparum, 24.6% P.vivax and 17.7% mixed infections.,Sensitivity of health center microscopists for any malaria species was >90% in five health centers (four of which had the highest prevalence), >70% in nine centers and 44% in one site with lowest prevalence.,Specificity for health center microscopy was very good (>95%) in all centers.,For ParaScreen RDT, sensitivity was ≥90% in three centers, ≥70% in six and <60% in four centers.,Specificity was ≥90% in all centers except one where it was 85%.,Health center microscopists performed well in nine of the ten health centers; while for ParaScreen RDT they performed well in only six centers.,Overall the accuracy of local microscopy exceeded that of RDT for all outcomes.,This study supports the introduction of RDTs only if accompanied by appropriate training, frequent supervision and quality control at all levels.,Deficiencies in RDT use at some health centers must be rectified before universal replacement of good routine microscopy with RDTs.,Maintenance and strengthening of good quality microscopy remains a priority at health center level.

Reactive case detection (RCD) is an integral part of many malaria control and elimination programmes and can be conceived of as a way of gradually decreasing transmission.,However, it is unclear under what circumstances RCD may have a substantial impact on prevalence, how likely it is to lead to local elimination, or how effective it needs to be to prevent reintroduction after transmission has been interrupted.,Analyses and simulations of a discrete time compartmental susceptible-infectious-susceptible (SIS) model were used to understand the mechanisms of how RCD changes transmission dynamics and estimate the impact of RCD programmes in a range of settings with varying patterns of transmission potential and programme characteristics.,Prevalence survey data from recent studies in Zambia were used to capture the effects of spatial clustering of patent infections.,RCD proved most effective at low prevalence.,Increasing the number of index cases followed was more important than increasing the number of neighbours tested per index case.,Elimination was achieved only in simulations of situations with very low transmission intensity and following many index cases.,However, RCD appears to be helpful in maintaining the disease-free state after achieving malaria elimination (through other interventions).,RCD alone can eliminate malaria in only a very limited range of settings, where transmission potential is very low, and improving the coverage of RCD has little effect on this range.,In other settings, it is likely to reduce disease burden.,RCD may also help maintain the disease-free state in the face of imported infections.,Prevalence survey data can be used to estimate a targeting ratio (the ratio of prevalence found through RCD to that in the general population) which is an important determinant of the effect of RCD.,The online version of this article (10.1186/s12936-019-2882-z) contains supplementary material, which is available to authorized users.

Case investigation and reactive case detection (RACD) activities are widely-used in low transmission settings to determine the suspected origin of infection and identify and treat malaria infections nearby to the index patient household.,Case investigation and RACD activities are time and resource intensive, include methodologies that vary across eliminating settings, and have no standardized metrics or tools available to monitor and evaluate them.,In response to this gap, a simple programme tool was developed for monitoring and evaluating (M&E) RACD activities and piloted by national malaria programmes.,During the development phase, four modules of the RACD M&E tool were created to assess and evaluate key case investigation and RACD activities and costs.,A pilot phase was then carried out by programme implementers between 2013 and 2015, during which malaria surveillance teams in three different settings (China, Indonesia, Thailand) piloted the tool over a period of 3 months each.,This study describes summary results of the pilots and feasibility and impact of the tool on programmes.,All three study areas implemented the RACD M&E tool modules, and pilot users reported the tool and evaluation process were helpful to identify gaps in RACD programme activities.,In the 45 health facilities evaluated, 71.8% (97/135; min 35.3-max 100.0%) of the proper notification and reporting forms and 20.0% (27/135; min 0.0-max 100.0%) of standard operating procedures (SOPs) were available to support malaria elimination activities.,The tool highlighted gaps in reporting key data indicators on the completeness for malaria case reporting (98.8%; min 93.3-max 100.0%), case investigations (65.6%; min 61.8-max 78.4%) and RACD activities (70.0%; min 64.7-max 100.0%).,Evaluation of the SOPs showed that knowledge and practices of malaria personnel varied within and between study areas.,Average monthly costs for conducting case investigation and RACD activities showed variation between study areas (min USD $844.80-max USD $2038.00) for the malaria personnel, commodities, services and other costs required to carry out the activities.,The RACD M&E tool was implemented in the three pilot areas, identifying key gaps that led to impacts on programme decision making.,Study findings support the need for routine M&E of malaria case reporting, case investigation and RACD activities.,Scale-up of the RACD M&E tool in malaria-eliminating settings will contribute to improved programme performance to the high level that is required to reach elimination.,The online version of this article (doi:10.1186/s12936-017-1991-9) contains supplementary material, which is available to authorized users.

Japan is one of the few countries believed to have eliminated soil-transmitted helminths (STHs).,In 1949, the national prevalence of Ascaris lumbricoides was 62.9%, which decreased to 0.6% in 1973 due to improvements in infrastructure, socioeconomic status, and the implementation of national STH control measures.,The Parasitosis Prevention Law ended in 1994 and population-level screening ceased in Japan; therefore, current transmission status of STH in Japan is not well characterized.,Sporadic cases of STH infections continue to be reported, raising the possibility of a larger-scale recrudescence of STH infections.,Given that traditional microscopic detection methods are not sensitive to low-intensity STH infections, we conducted targeted prevalence surveys using sensitive PCR-based assays to evaluate the current STH-transmission status and to describe epidemiological characteristics of areas of Japan believed to have achieved historical elimination of STHs.,Stool samples were collected from 682 preschool- and school-aged children from six localities of Japan with previously high prevalence of STH.,Caregivers of participants completed a questionnaire to ascertain access to water, sanitation and hygiene (WASH), and potential exposures to environmental contamination.,For fecal testing, multi-parallel real-time PCR assays were used to detect infections of Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale and Trichuris trichiura.,Among the 682 children, no positive samples were identified, and participants reported high standards of WASH.,To our knowledge, this is the first STH-surveillance study in Japan to use sensitive molecular techniques for STH detection.,The results suggest that recrudescence of STH infections has not occurred, and that declines in prevalence have been sustained in the sampled areas.,These findings suggest that reductions in prevalence below the elimination thresholds, suggestive of transmission interruption, are possible.,Additionally, this study provides circumstantial evidence that multi-parallel real-time PCR methods are applicable for evaluating elimination status in areas where STH prevalence is extremely low.

In recent years, an increased focus has been placed upon the possibility of the elimination of soil-transmitted helminth (STH) transmission using various interventions including mass drug administration.,The primary diagnostic tool recommended by the WHO is the detection of STH eggs in stool using the Kato-Katz (KK) method.,However, detecting infected individuals using this method becomes increasingly difficult as the intensity of infection decreases.,Newer techniques, such as qPCR, have been shown to have greater sensitivity than KK, especially at low prevalence.,However, the impact of using qPCR on elimination thresholds is yet to be investigated.,In this paper, we aim to quantify how the sensitivity of these two diagnostic tools affects the optimal prevalence threshold at which to declare the interruption of transmission with a defined level of confidence.,A stochastic, individual-based STH transmission model was used in this study to simulate the transmission dynamics of Ascaris and hookworm.,Data from a Kenyan deworming study were used to parameterize the diagnostic model which was based on egg detection probabilities.,The positive and negative predictive values (PPV and NPV) were calculated to assess the quality of any given threshold, with the optimal threshold value taken to be that at which both were maximised.,The threshold prevalence of infection values for declaring elimination of Ascaris transmission were 6% and 12% for KK and qPCR respectively.,For hookworm, these threshold values are lower at 0.5% and 2% respectively.,Diagnostic tests with greater sensitivity are becoming increasingly important as we approach the elimination of STH transmission in some regions of the world.,For declaring the elimination of transmission, using qPCR to diagnose STH infection results in the definition of a higher prevalence, than when KK is used.

In the murine model of cerebral malaria caused by P. berghei ANKA (PbA), parasite-specific CD8+ T cells directly induce pathology and have long been hypothesized to kill brain endothelial cells that have internalized PbA antigen.,We previously reported that brain microvessel fragments from infected mice cross-present PbA epitopes, using reporter cells transduced with epitope-specific T cell receptors.,Here, we confirm that endothelial cells are the population responsible for cross-presentation in vivo, not pericytes or microglia.,PbA antigen cross-presentation by primary brain endothelial cells in vitro confers susceptibility to killing by CD8+ T cells from infected mice.,IFNγ stimulation is required for brain endothelial cross-presentation in vivo and in vitro, which occurs by a proteasome- and TAP-dependent mechanism.,Parasite strains that do not induce cerebral malaria were phagocytosed and cross-presented less efficiently than PbA in vitro.,The main source of antigen appears to be free merozoites, which were avidly phagocytosed.,A human brain endothelial cell line also phagocytosed P. falciparum merozoites.,Besides being the first demonstration of cross-presentation by brain endothelial cells, our results suggest that interfering with merozoite phagocytosis or antigen processing may be effective strategies for cerebral malaria intervention.

Decreased nitric oxide (NO) and hypoargininemia are associated with severe falciparum malaria and may contribute to severe disease.,Intravenous L-arginine increases endothelial NO in moderately-severe malaria (MSM) without adverse effects.,The safety, efficacy and pharmacokinetics of L-arginine or other agents to improve NO bioavailability in severe malaria have not been assessed.,In an open-label pilot study of L-arginine in adults with severe malaria (ARGISM-1 Study), patients were randomized to 12 g L-arginine hydrochloride or saline over 8 hours together with intravenous artesunate.,Vital signs, selected biochemical measures (including blood lactate and L-arginine) and endothelial NO bioavailability (using reactive hyperemia peripheral arterial tonometry [RH-PAT]) were assessed serially.,Pharmacokinetic analyses of L-arginine concentrations were performed using NONMEM.,Six patients received L-arginine and two saline infusions.,There were no deaths in either group.,There were no changes in mean systolic (SBP) and diastolic blood pressure (DBP) or other vital signs with L-arginine, although a transient but clinically unimportant mean maximal decrease in SBP of 14 mmHg was noted.,No significant changes in mean potassium, glucose, bicarbonate, or pH were seen, with transient mean maximal increases in plasma potassium of 0.3 mmol/L, and mean maximal decreases in blood glucose of 0.8 mmol/L and bicarbonate of 2.3 mEq/L following L-arginine administration.,There was no effect on lactate clearance or RH-PAT index.,Pharmacokinetic modelling (n = 4) showed L-arginine concentrations 40% lower than predicted from models developed in MSM.,In the first clinical trial of an adjunctive treatment aimed at increasing NO bioavailability in severe malaria, L-arginine infused at 12 g over 8 hours was safe, but did not improve lactate clearance or endothelial NO bioavailability.,Future studies may require increased doses of L-arginine.,ClinicalTrials.gov NTC00616304

In Cambodia, malaria transmission is low and most cases occur in forested areas.,Sero-epidemiological techniques can be used to identify both areas of ongoing transmission and high-risk groups to be targeted by control interventions.,This study utilizes repeated cross-sectional data to assess the risk of being malaria sero-positive at two consecutive time points during the rainy season and investigates who is most likely to sero-convert over the transmission season.,In 2005, two cross-sectional surveys, one in the middle and the other at the end of the malaria transmission season, were carried out in two ecologically distinct regions in Cambodia.,Parasitological and serological data were collected in four districts.,Antibodies to Plasmodium falciparum Glutamate Rich Protein (GLURP) and Plasmodium vivax Merozoite Surface Protein-119 (MSP-119) were detected using Enzyme Linked Immunosorbent Assay (ELISA).,The force of infection was estimated using a simple catalytic model fitted using maximum likelihood methods.,Risks for sero-converting during the rainy season were analysed using the Classification and Regression Tree (CART) method.,A total of 804 individuals participating in both surveys were analysed.,The overall parasite prevalence was low (4.6% and 2.0% for P. falciparum and 7.9% and 6.0% for P. vivax in August and November respectively).,P. falciparum force of infection was higher in the eastern region and increased between August and November, whilst P. vivax force of infection was higher in the western region and remained similar in both surveys.,In the western region, malaria transmission changed very little across the season (for both species).,CART analysis for P. falciparum in the east highlighted age, ethnicity, village of residence and forest work as important predictors for malaria exposure during the rainy season.,Adults were more likely to increase their antibody responses to P. falciparum during the transmission season than children, whilst members of the Charay ethnic group demonstrated the largest increases.,In areas of low transmission intensity, such as in Cambodia, the analysis of longitudinal serological data enables a sensitive evaluation of transmission dynamics.,Consecutive serological surveys allow an insight into spatio-temporal patterns of malaria transmission.,The use of CART enabled multiple interactions to be accounted for simultaneously and permitted risk factors for exposure to be clearly identified.

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

The malaria burden has decreased significantly in recent years in Africa through the widespread use of artemisinin-based combination therapy (ACT) and long-lasting insecticide-treated nets (LLINs).,However, the occurrence of malaria resurgences, the loss of immunity of exposed populations constitute among other factors, serious concerns about the future of malaria elimination efforts.,This study investigated the evolution of malaria morbidity in Dielmo (Senegal) before and after the implementation of LLINs.,A longitudinal study was carried out in Dielmo over eight years, from July 2007 to July 2015.,In July 2008, LLINs were offered to all villagers, and in July 2011 and August 2014 the LLINs were renewed.,A survey on LLINs use was done each quarter of the year.,Thick smears stained with Giemsa, a rapid diagnostic test (RDT) and quantitative polymerase chain reaction (PCR) methods were performed for all cases of fever to assess malaria clinical attacks.,Malaria cases were treated with ACT since June 2006.,Malaria morbidity has decreased significantly since the implementation of LLINs in Dielmo, together with ACT.,However, malaria resurgences have occurred twice during the seven years of LLINs use.,These resurgences occurred the first time during the third year after the introduction of LLINs (aIRR (adjusted incidence-rate ratio) [95%CI] = 5.90 [3.53; 9.88] p< 0.001) and a second time during the third year after the renewal of LLINs (aIRR [95%CI] = 5.60 [3.34; 9.39] p< 0.001).,Sixty-nine percent (69%) of the nets tested for their long-lasting insecticidal activity remained effective after 3 years of use.,Good management of malaria cases by the use of ACT as first-line treatment against malaria in addition to the use of LLINs has significantly reduced malaria in Dielmo and allowed to reach the phase of pre-elimination of the disease.,However, the occurrence of malaria resurgences raised serious concerns about malaria elimination, which would require additional tools in this village.

Control efforts towards malaria due to Plasmodium falciparum significantly decreased the incidence of the disease in many endemic countries including Senegal.,Surprisingly, in Kedougou (southeastern Senegal) P. falciparum malaria remains highly prevalent and the relative contribution of other Plasmodium species to the global malaria burden is very poorly documented, partly due to the low sensitivity of routine diagnostic tools.,Molecular methods offer better estimate of circulating Plasmodium species in a given area.,A molecular survey was carried out to document circulating malaria parasites in Kedougou region.,A total of 263 long-term stored sera obtained from patients presenting with acute febrile illness in Kedougou between July 2009 and July 2013 were used for malaria parasite determination.,Sera were withdrawn from a collection established as part of a surveillance programme of arboviruses infections in the region.,Plasmodium species were characterized by a nested PCR-based approach targeting the 18S small sub-unit ribosomal RNA genes of Plasmodium spp.,Of the 263 sera screened in this study, Plasmodium genomic DNA was amplifiable by nested PCR from 62.35% (164/263) of samples.,P. falciparum accounted for the majority of infections either as single in 85.97% (141/164) of Plasmodium-positive samples or mixed with Plasmodium ovale (11.58%, 19/164) or Plasmodium vivax (1.21%, 2/164).,All 19 (11.58%) P. ovale-infected patients were mixed with P. falciparum, while no Plasmodium malariae was detected in this survey.,Four patients (2.43%) were found to be infected by P. vivax, two of whom were mixed with P. falciparum.,P. vivax infections originated from Bandafassi and Ninefesha villages and concerned patients aged 4, 9, 10, and 15 years old, respectively.,DNA sequences alignment and phylogenetic analysis demonstrated that sequences from Kedougou corresponded to P. vivax, therefore confirming the presence of P. vivax infections in Senegal.,The results confirm the high prevalence of P. falciparum in Kedougou and provide the first molecular evidence of P. vivax infections in Senegal.,These findings pave the ways for further investigations of P. vivax infections in Senegal and its contribution to the global burden of malaria disease before targeted strategies can be deployed.

The intestinal epithelium is the first natural barrier against Trichinella spiralis larval invasion, but the mechanism of larval invasion of the gut epithelium is not fully elucidated.,The aim of this study was to investigate whether the excretory/secretory proteins (ESPs) of T. spiralis intestinal infective larvae (IIL) degrade tight junction (TJ) proteins, to assess the main ESP proteases hydrolysing TJ proteins using various enzyme inhibitors and to define the key invasive factors in IIL invasion of the gut epithelium.,The results of immunofluorescence, Western blot and Transwell assays showed that serine proteases and cysteine proteases in the ESPs played main roles in hydrolysing occludin, claudin-1 and E-cad and upregulating claudin-2 expression.,Challenge infection results showed that IIL expulsion from the gut at 12 hpi was significantly higher in mice which were infected with muscle larvae (ML) treated with a single inhibitor (PMSF, E-64, 1,10-Phe or pepstatin) or various mixtures containing PMSF and E-64 than in mice in the PBS group or the groups treated with an inhibitor mixture not containing PMSF and E-64 (P < 0.0001).,At 6 days post-infection, mice which were infected with ML treated with PMSF, E-64, 1,10-Phe or pepstatin exhibited 56.30, 64.91, 26.42 and 31.85% reductions in intestinal adult worms compared to mice in the PBS group (P < 0.0001).,The results indicate that serine proteases and cysteine proteases play key roles in T. spiralis IIL invasion, growth and survival in the host and that they may be main candidate target molecules for vaccines against larval invasion and development.

The aim of this study was to study the molecular characteristics of Trichinella spiralis galectin (Tsgal) and interactions between Tsgal and host’s intestinal epithelial cells (IECs).,The functional domain of Tsgal was cloned and expressed in an E. coli system.,The Tsgal was 97.1% identity to the galectin of T. nativa and 20.8% identity to the galectin-8 of humans.,Conserved domain analysis revealed that Tsgal belongs to TR-type galectin and has two carbon recognized domain.,The rTsgal with 29.1 kDa could be recognized by T. spiralis-infected mice at 42 days post-infection (dpi).,The transcription and expression of Tsgal gene was detected by RT-PCR and Western blotting in all T. spiralis developmental stages (intestinal infective larvae, adult worms, newborn larvae, and muscle larvae).,The IFA results revealed that Tsgal was mainly located at the cuticles and stichosomes of T. spiralis larvae (ML, IIL and NBL).,The rTsgal had hemagglutinating function for erythrocytes from human, rabbit and mouse.,The results of Far Western blot and confocal microscopy indicated there was specific binding between rTsgal and IECs, and the binding was located the membrane and cytoplasm of the IECs.,Out of four sugars (sucrose, glucose, lactose and maltose), only lactose was able to inhibit the rTsgal agglutinating role for human type B erythrocytes.,Moreover, the rTsgal could promote the larval invasion of IECs, while the anti-rTsgal serum inhibited the larval invasion.,These results demonstrated that Tsgal might participate in the T. spiralis invasion of intestinal epithelium in early infection stage.

As indigenous malaria has decreased over recent decades, the increasing number of imported malaria cases has provided a new challenge for China.,The proportion of imported cases due to Plasmodium ovale has increased during this time, and the difference between P. ovale curtisi and P. ovale wallikeri is of importance.,To better understand P. ovale epidemiology and the differences between the two subspecies, information on imported malaria in Henan Province was collected during 2010-2017.,We carried out a descriptive study to analyze the prevalence, proportion, distribution, and origin of P. o. curtisi and P. o. wallikeri.,It showed that imported P. ovale spp. accounts for a large proportion of total malaria cases in Henan Province, even more than that of P. vivax.,This suggests that the proportion of P. ovale cases is underestimated in Africa.,Among these cases, the latency period of P. o. curtisi was significantly longer than that of P. o. wallikeri.,More attention should be paid to imported ovale malaria to avoid the reintroduction of these two subspecies into China.

Expanded malaria control efforts in Sénégal have resulted in increased use of rapid diagnostic tests (RDT) to identify the primary disease-causing Plasmodium species, Plasmodium falciparum.,However, the type of RDT utilized in Sénégal does not detect other malaria-causing species such as Plasmodium ovale spp., Plasmodium malariae, or Plasmodium vivax.,Consequently, there is a lack of information about the frequency and types of malaria infections occurring in Sénégal.,This study set out to better determine whether species other than P. falciparum were evident among patients evaluated for possible malaria infection in Kédougou, Sénégal.,Real-time polymerase chain reaction speciation assays for P. vivax, P. ovale spp., and P. malariae were developed and validated by sequencing and DNA extracted from 475 Plasmodium falciparum-specific HRP2-based RDT collected between 2013 and 2014 from a facility-based sample of symptomatic patients from two health clinics in Kédougou, a hyper-endemic region in southeastern Sénégal, were analysed.,Plasmodium malariae (n = 3) and P. ovale wallikeri (n = 2) were observed as co-infections with P. falciparum among patients with positive RDT results (n = 187), including one patient positive for all three species.,Among 288 negative RDT samples, samples positive for P. falciparum (n = 24), P. ovale curtisi (n = 3), P. ovale wallikeri (n = 1), and P. malariae (n = 3) were identified, corresponding to a non-falciparum positivity rate of 2.5%.,These findings emphasize the limitations of the RDT used for malaria diagnosis and demonstrate that non-P. falciparum malaria infections occur in Sénégal.,Current RDT used for routine clinical diagnosis do not necessarily provide an accurate reflection of malaria transmission in Kédougou, Sénégal, and more sensitive and specific methods are required for diagnosis and patient care, as well as surveillance and elimination activities.,These findings have implications for other malaria endemic settings where species besides P. falciparum may be transmitted and overlooked by control or elimination activities.,The online version of this article (doi:10.1186/s12936-016-1661-3) contains supplementary material, which is available to authorized users.

In tegumentary leishmaniasis caused by Leishmania braziliensis, there is evidence that increased production of IFN-γ, TNF-α and absence of IL-10 is associated with strong inflammatory reaction and with tissue destruction and development of the lesions observed in cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML).,We evaluate the role of regulatory cytokines and cytokine antagonists in the down-regulation of immune response in L. braziliensis infection.,Peripheral blood mononuclear cells from CL and ML were stimulated with soluble Leishmania antigen in the presence or absence of regulatory cytokines (IL-10, IL-27 and TGF-β) or antagonists of cytokines (α-TNF-α and α-IFN-γ).,Cytokines production (IL-10, IL-17, TNF-α and IFN-γ) was measured by ELISA.,IL-10 and TGF-β downmodulate TNF-α and IL-17 production, whereas IL-27 had no effect in the production of TNF-α, IFN-γ and IL-17 in these patients.,Neutralization of TNF-α decreased IFN-γ level and the neutralization of IFN-γ decreased TNF-α level and increased IL-10 production.,This study demonstrate that IL-10 and TGF-β are cytokines that appear to be more involved in modulation of immune response in CL and ML patients.,IL-10 might have a protective role, since the neutralization of IFN-γ decreases the production of TNF-α in an IL-10-dependent manner.

The main clinical forms of tegumentary leishmaniasis are cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML).,L.braziliensis infection is characterized by an exaggerated production of IFN-gamma and TNF-alpha, cytokines involved in parasite destruction, but also in the pathology.,Maintenance of an antigen-specific immune response may be important for resistance to re-infection and will contribute for vaccine development.,In the present work we investigated the immune response in CL and ML cured individuals.,Participants in the present study included 20 CL and 20 ML patients, who were evaluated prior to, as well as 2 to 15 years after therapy.,IFN-gamma, IL-2 and TNF-alpha production were determined by ELISA in supernatants of mononuclear cells stimulated with soluble L.braziliensis antigen (SLA).,The frequency of memory CD4+ T cell populations was determined by FACS.,Here we show that the majority of CL and ML patients did not produce in vitro IFN-gamma in response to SLA after cure.,In the cured individuals who responded to SLA, effector memory (CD45RA-CCR7-) CD4+ T cells were the ones producing IFN-gamma.,Because a large percent of CL and ML cured patients lost SLA-induced IFN-gamma production in peripheral blood, we performed Leishmania skin test (LST).,A positive LST was found in 87.5% and 100% of CL and ML cured individuals, respectively, who did not produce IFN-gamma or IL-2 in vitro.,This study shows that in spite of losing in vitro antigen-specific response to Leishmania, cured CL and ML subjects retain the ability to respond to SLA in vivo.,These findings indicate that LST, rather than IFN-gamma production, may be a better assessment of lasting immunity to leishmaniasis in human studies, and thus a better tool for assessing immunization after vaccine.,Furthermore, in cured individuals which maintains Leishmania-specific IFN-gamma production, effector memory CD4+ T cells were the main source of this cytokine.

Many parts of Africa have witnessed reductions in Plasmodium falciparum transmission over the last 15 years.,Since immunity to malaria is acquired more rapidly at higher transmission, the slower acquisition of immunity at lower transmission may partially offset the benefits of reductions in transmission.,We examined the clinical spectrum of disease and predictors of mortality after sustained changes in transmission intensity, using data collected from 1989 to 2016.,We conducted a temporal observational analysis of 18,000 children, aged 14 days to 14 years old, who were admitted to Kilifi County Hospital, Kenya, from 1989 to 2016 with malaria.,We describe the trends over time of the clinical and laboratory criteria for severe malaria and associated risk of mortality.,During the time periods 1989-2003, 2004-2008, and 2009-2016, Kilifi County Hospital admitted averages of 657, 310, and 174 cases of severe malaria per year including averages of 48, 14, and 12 malaria-associated deaths per year, respectively.,The median ages in years of children admitted with cerebral malaria, severe anaemia, and malaria-associated mortality were 3.0 (95% confidence interval (CI) 2.2-3.9), 1.1 (95% CI 0.9-1.4), and 1.1 (95% CI 0.3-2.2) in the year 1989, rising to 4.9 (95% CI 3.9-5.9), 3.8 (95% CI 2.5-7.1), and 5 (95% CI 3.3-6.3) in the year 2016.,The ratio of children with cerebral malaria to severe anaemia rose from 1:2 before 2004 to 3:2 after 2009.,Hyperparasitaemia was a risk factor for death after 2009 but not in earlier time periods.,Despite the evidence of slower acquisition of immunity, continued reductions in the numbers of cases of severe malaria resulted in lower overall mortality.,Our temporal data are limited to a single site, albeit potentially applicable to a secular trend present in many parts of Africa.,The online version of this article (10.1186/s12916-019-1359-9) contains supplementary material, which is available to authorized users.

Mild cases of malaria, pneumonia and diarrhea are readily treatable with complete recovery and with inexpensive and widely available first-line drugs.,However, treatment is complicated and expensive, and mortality is higher when children present to the hospital with severe forms of these illnesses.,We studied how care seeking behaviours and other factors contributed to severity of malaria, pneumonia and diarrhoea among children less than five years in rural Tanzania.,We interviewed consecutive care-takers of children diagnosed with malaria, pneumonia and/or diarrhea at Korogwe and Muheza district hospitals, in north-eastern Tanzania, between July 2009 and January 2010, and compared characteristics of children presenting with severe and those with non-severe disease.,A total of 293 children with severe and 190 with non-severe disease were studied.,We found persistent associations between severity of disease and caretaker’s lack of formal education (OR 6.6; 95% confidence interval (CI) 2.7-15.8) compared to those with post-primary education, middle compared to high socio-economic status (OR 1.9; 95% CI 1.2-3.2), having 4 or more children compared to having one child (OR 2.5; 95% CI 1.4-4.5), having utilized a nearer primary health care (PHC) facility for the same illness compared to having not (OR 5.2; 95% CI 3.0-9.1), and having purchased the first treatment other than paracetamol from local or drug shops compared to when the treatment was obtained from the public hospitals for the first time (OR 3.2; 95% CI 1.9-5.2).,The old officially abandoned first line anti-malaria drug Sulfadoxin-pyrimethamine (SP) was found to still be in use for the treatment of malaria and was significantly associated with childrens’ presentation to the hospital with severe malaria (OR 12.5; 95% CI 1.6-108.0).,Our results indicate that caretakers with no formal education, with lower SES and with many children can be target groups for interventions in order to further reduce child mortality from treatable illnesses.,Furthermore, the quality of the available drug shops and PHC facilities need to be closely monitored.

The growth potential of the tumor-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly linked to the nature/function of the periparasitic host immune-mediated processes.,We previously showed that Fibrinogen-like-protein 2 (FGL2), a novel CD4+CD25+ Treg effector molecule, was over-expressed in the liver of mice experimentally infected with E. multilocularis.,However, little is known about its contribution to the control of this chronic helminth infection.,Key parameters for infection outcome in E. multilocularis-infected fgl2-/- (AE-fgl2-/-) and wild type (AE-WT) mice at 1 and 4 month(s) post-infection were (i) parasite load (i. e. wet weight of parasitic metacestode tissue), and (ii) parasite cell proliferation as assessed by determining E. multilocularis 14-3-3 gene expression levels.,Serum FGL2 levels were measured by ELISA.,Spleen cells cultured with ConA for 48h or with E. multilocularis Vesicle Fluid (VF) for 96h were analyzed ex-vivo and in-vitro.,In addition, spleen cells from non-infected WT mice were cultured with rFGL2/anti-FGL2 or rIL-17A/anti-IL-17A for further functional studies.,For Treg-immune-suppression-assays, purified CD4+CD25+ Treg suspensions were incubated with CD4+ effector T cells in the presence of ConA and irradiated spleen cells as APCs.,Flow cytometry and qRT-PCR were used to assess Treg, Th17-, Th1-, Th2-type immune responses and maturation of dendritic cells.,We showed that AE-fgl2-/- mice exhibited (as compared to AE-WT-animals) (a) a significantly lower parasite load with reduced proliferation activity, (b) an increased T cell proliferative response to ConA, (c) reduced Treg numbers and function, and (d) a persistent capacity of Th1 polarization and DC maturation.,FGL2 appears as one of the key players in immune regulatory processes favoring metacestode survival by promoting Treg cell activity and IL-17A production that contributes to FGL2-regulation.,Prospectively, targeting FGL2 could be an option to develop an immunotherapy against AE and other chronic parasitic diseases.

Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus.,Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metacestodes.,In the experimental model of secondary cystic echinococcosis mice react against protoscoleces producing inefficient immune responses, allowing parasites to develop into cysts.,Although the chronic phase of infection has been analyzed in depth, early immune responses at the site of infection establishment, e.g., peritoneal cavity, have not been well studied.,Because during early stages of infection parasites are thought to be more susceptible to immune attack, this work focused on the study of cellular and molecular events triggered early in the peritoneal cavity of infected mice.,Data obtained showed disparate behaviors among subpopulations within the peritoneal lymphoid compartment.,Regarding B cells, there is an active molecular process of plasma cell differentiation accompanied by significant local production of specific IgM and IgG2b antibodies.,In addition, peritoneal NK cells showed a rapid increase with a significant percentage of activated cells.,Peritoneal T cells showed a substantial increase, with predominance in CD4+ T lymphocytes.,There was also a local increase in Treg cells.,Finally, cytokine response showed local biphasic kinetics: an early predominant induction of Th1-type cytokines (IFN-γ, IL-2 and IL-15), followed by a shift toward a Th2-type profile (IL-4, IL-5, IL-6, IL-10 and IL-13).,Results reported here open new ways to investigate the involvement of immune effectors players in E. granulosus establishment, and also in the sequential promotion of Th1- toward Th2-type responses in experimental secondary cystic echinococcosis.,These data would be relevant for designing rational therapies based on stimulation of effective responses and blockade of evasion mechanisms.

Infectious pathogens contribute to the development of autoimmune disorders, but the mechanisms connecting these processes are incompletely understood.,Here we show that Plasmodium DNA induces autoreactive responses against erythrocytes by activating a population of B cells expressing CD11c and the transcription factor T-bet, which become major producers of autoantibodies that promote malarial anaemia.,Additionally, we identify parasite DNA-sensing through Toll-like receptor 9 (TLR9) along with inflammatory cytokine receptor IFN-γ receptor (IFN-γR) as essential signals that synergize to promote the development and appearance of these autoreactive T-bet+ B cells.,The lack of any of these signals ameliorates malarial anaemia during infection in a mouse model.,We also identify both expansion of T-bet+ B cells and production of anti-erythrocyte antibodies in ex vivo cultures of naive human peripheral blood mononuclear cells (PBMC) exposed to P. falciprum infected erythrocyte lysates.,We propose that synergistic TLR9/IFN-γR activation of T-bet+ B cells is a mechanism underlying infection-induced autoimmune-like responses.,Autoimmune anaemia often accompanies Plasmodium infection and malaria, but how anaemia is induced is still unclear.,Here the authors show that Plasmodium DNA, together with interferon-γ, can activate B cells to induce auto-antibodies that recognize red blood cells and promote their removal to contribute to anaemia onset.

Humoral immunity consists of pre-existing antibodies expressed by long-lived plasma cells and rapidly reactive memory B cells (MBC).,Recent studies of MBC development and function after protein immunization have uncovered significant MBC heterogeneity.,To clarify functional roles for distinct MBC subsets during malaria infection, we generated tetramers that identify Plasmodium-specific MBCs in both humans and mice.,Long-lived murine Plasmodium-specific MBCs consisted of three populations: somatically hypermutated immunoglobulin M+ (IgM+) and IgG+ MBC subsets and an unmutated IgD+ MBC population.,Rechallenge experiments revealed that high affinity, somatically hypermutated Plasmodium-specific IgM+ MBCs proliferated and gave rise to antibody-secreting cells that dominated the early secondary response to parasite rechallenge.,IgM+ MBCs also gave rise to T cell-dependent IgM+ and IgG+B220+CD138+ plasmablasts or T cell-independent B220−CD138+ IgM+ plasma cells.,Thus, even in competition with IgG+ MBCs, IgM+ MBCs are rapid, plastic, early responders to a secondary Plasmodium rechallenge and should be targeted by vaccine strategies.,•Tetramers allow analyses of endogenous Plasmodium-specific B cells in mice and humans•Three phenotypically distinct MBC populations form after murine malaria infection•Plasmodium-specific IgM+ MBCs are somatically hypermutated and high affinity•Plastic IgM+ memory B cells dominate the early response to malaria rechallenge,Tetramers allow analyses of endogenous Plasmodium-specific B cells in mice and humans,Three phenotypically distinct MBC populations form after murine malaria infection,Plasmodium-specific IgM+ MBCs are somatically hypermutated and high affinity,Plastic IgM+ memory B cells dominate the early response to malaria rechallenge,Heterogeneous types of memory B cells are present in both humans and mice, yet it is unclear how different MBC subsets form or function in response to infection.,Pepper and colleagues reveal that phenotypically and functionally distinct populations of polyclonal Plasmodium-specific MBCs form in response to infection and somatically hypermutated, high-affinity, plastic IgM+ memory B cells dominate the early memory response to malaria rechallenge.

In ELISAs, sera of individuals infected by Trypanosoma cruzi show absorbance values above a cut-off value.,The cut-off is generally computed by means of formulas that need absorbance readings of negative (and sometimes positive) controls, which are included in the titer plates amongst the unknown samples.,When no controls are available, other techniques should be employed such as change-point analysis.,The method was applied to Bolivian dog sera processed by ELISA to diagnose T. cruzi infection.,In each titer plate, the change-point analysis estimated a step point which correctly discriminated among known positive and known negative sera, unlike some of the six usual cut-off formulas tested.,To analyse the ELISAs results, the change-point method was as good as the usual cut-off formula of the form “mean + 3 standard deviation of negative controls”.,Change-point analysis is therefore an efficient alternative method to analyse ELISA absorbance values when no controls are available.

Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus.,Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metacestodes.,In the experimental model of secondary cystic echinococcosis mice react against protoscoleces producing inefficient immune responses, allowing parasites to develop into cysts.,Although the chronic phase of infection has been analyzed in depth, early immune responses at the site of infection establishment, e.g., peritoneal cavity, have not been well studied.,Because during early stages of infection parasites are thought to be more susceptible to immune attack, this work focused on the study of cellular and molecular events triggered early in the peritoneal cavity of infected mice.,Data obtained showed disparate behaviors among subpopulations within the peritoneal lymphoid compartment.,Regarding B cells, there is an active molecular process of plasma cell differentiation accompanied by significant local production of specific IgM and IgG2b antibodies.,In addition, peritoneal NK cells showed a rapid increase with a significant percentage of activated cells.,Peritoneal T cells showed a substantial increase, with predominance in CD4+ T lymphocytes.,There was also a local increase in Treg cells.,Finally, cytokine response showed local biphasic kinetics: an early predominant induction of Th1-type cytokines (IFN-γ, IL-2 and IL-15), followed by a shift toward a Th2-type profile (IL-4, IL-5, IL-6, IL-10 and IL-13).,Results reported here open new ways to investigate the involvement of immune effectors players in E. granulosus establishment, and also in the sequential promotion of Th1- toward Th2-type responses in experimental secondary cystic echinococcosis.,These data would be relevant for designing rational therapies based on stimulation of effective responses and blockade of evasion mechanisms.

Toxoplasma gondii is a eukaryotic parasite that forms latent cysts in the brain of immunocompetent individuals.,The latent parasite infection of the immune-privileged central nervous system is linked to most complications.,With no drug currently available to eliminate the latent cysts in the brain of infected hosts, the consequences of neurons' long-term infection are unknown.,It has long been known that T. gondii specifically differentiates into a latent form (bradyzoite) in neurons, but how the infected neuron responds to the infection remains to be elucidated.,We have established a new in vitro model resulting in the production of mature bradyzoite cysts in brain cells.,Using dual, host and parasite RNA-seq, we characterized the dynamics of differentiation of the parasite, revealing the involvement of key pathways in this process.,Moreover, we identified how the infected brain cells responded to the parasite infection revealing the drastic changes that take place.,We showed that neuronal-specific pathways are strongly affected, with synapse signalling being particularly affected, especially glutamatergic synapse signalling.,The establishment of this new in vitro model allows investigating both the dynamics of parasite differentiation and the specific response of neurons to long-term infection by this parasite.

Toxoplasma gondii is a widely prevalent protozoan parasite member of the phylum Apicomplexa.,It causes disease in humans with clinical outcomes ranging from an asymptomatic manifestation to eye disease to reproductive failure and neurological symptoms.,In farm animals, and particularly in sheep, toxoplasmosis costs the industry millions by profoundly affecting their reproductive potential.,As do all the parasites in the phylum, T. gondii parasites go through sexual and asexual replication in the context of an heteroxenic life cycle involving members of the Felidae family and any warm-blooded vertebrate as definitive and intermediate hosts, respectively.,During sexual replication, merozoites differentiate into female and male gametes; their combination gives rise to a zygotes which evolve into sporozoites that encyst and are shed in cat’s feces as environmentally resistant oocysts.,During zygote formation T. gondii parasites are diploid providing the parasite with a window of opportunity for genetic admixture making this a key step in the generation of genetic diversity.,In addition, oocyst formation and shedding are central to dissemination and environmental contamination with infectious parasite forms.,In this minireview we summarize the current state of the art on the process of gametogenesis.,We discuss the unique structures of macro and microgametes, an insight acquired through classical techniques, as well as the more recently attained molecular understanding of the routes leading up to these life forms by in vitro and in vivo systems.,We pose a number of unanswered questions and discuss these in the context of the latest findings on molecular cues mediating stage switching, and the implication for the field of newly available in vitro tools.

Malaria vector control in Tanzania is based on use of long-lasting insecticide treated nets (LLINs) and indoor residual spraying (IRS), which both rely on the use of chemical insecticides.,The effectiveness of these control tools is endangered by the development of insecticide resistance in the major malaria vectors.,This study was carried out to monitor the susceptibility status of major malaria vectors to insecticides used for IRS and LLINs in mainland Tanzania.,Mosquito larvae were collected in 20 sites of Tanzania mainland in 2015.,Phenotypic resistance was determined using standard WHO susceptibility tests.,Molecular assay were used to determine distribution of Anopheles gambiae sub-species.,A microplate assay approach was used for identifying enzyme levels on single mosquitoes from each sites compared with a susceptible reference strain, An. gambiae sensu stricto (s.s.),Kisumu strain.,Anopheles arabiensis was the dominant malaria specie in the country, accounting for 52% of the sibling species identified, while An. gambiae s.s. represented 48%.,In Arumeru site, the dominant species was An. arabiensis, which was resistant to both pyrethroids (permethrin and deltamethrin), and pirimiphos-methyl, and had significant elevated levels of GSTs, non-specific esterases, and oxidase enzymes.,An. arabiensis was also a dominant species in Kilombero and Kondoa sites, both were resistant to permethrin and deltamethrin with significant activity levels of oxidase enzymes.,Resistance to bendiocarb was recorded in Ngara site where specie composition is evenly distributed between An. gambiae s.s. and An.arabiensis.,Also bendiocarb resistance was recorded in Mbozi site, where An. gambiae s.s. is the dominant species.,Overall, this study confirmed resistance to all four insecticide classes in An. gambiae sensu lato in selected locations in Tanzania.,Results are discussed in relation to resistance mechanisms and the optimization of resistance management strategies.

Alternative long-lasting, practical and effective tools for applying insecticides on home walls against malaria vectors need to be developed.,The use of wall hangings made from netting on interior walls for aesthetic purposes is a common practice in rural communities.,Insecticide-treated net wall hangings can be produced in a long-lasting format and used in an approach that simulates indoor residual spraying (IRS).,The efficacy of net wall hangings (NWH) treated with the residual organophosphate insecticide, pirimiphos methyl (1 g/sq m), was evaluated in experimental huts against malaria vectors in Muheza, Tanzania.,To determine the optimum level of wall coverage required, NWH were tested on ceiling only, two walls, four walls, or four walls plus ceiling.,Comparison was made with deltamethrin-treated NWH on two walls.,Pirimiphos methyl (p-methyl)-treated NWH (on two walls) killed significantly higher proportions of anophelines (92% of Anopheles gambiae and 79% of Anopheles funestus) than the deltamethrin-treated NWH (15% of An. gambiae and 17% of An. funestus) (P < 0.001).,WHO susceptibility tests showed that the local vector population was susceptible to the organophosphates but resistant to pyrethroids.,Mortality rates were significantly higher in huts with p-methyl NWH on two walls (92% for An. gambiae and 79% for An. funestus) than on ceiling only (61% for An. gambiae and 62% for An. funestus, P < 0.05).,There was no improvement in mortality when wall coverage with p-methyl NWH increased beyond two walls.,Blood-feeding rates with p-methyl NWH were generally high across all the treatments (52-77%) and did not differ significantly from the control (64-67%).,There was no evidence of reduced blood-feeding or increased exiting with increase in wall coverage with p-methyl NWH.,Net wall hangings are an effective means of delivering insecticides in the domestic environment against malaria vectors.,They could be more practical and acceptable than IRS thus showing enormous potential for malaria vector control.,Appropriate binding or incorporation technology needs to be developed to enable the production of p-methyl NWH with residual activity lasting over a number of years.

In Jimma Zone, Ethiopia, the first-line treatment of uncomplicated falciparum malaria has been changed from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (AL) in 2006.,The objective of this study was to assess the effectiveness of AL in Jimma Zone two to three years after its broad introduction.,An open-label, single-arm, 42-day study of AL against falciparum malaria was conducted in four areas with moderate transmission in Jimma Zone between November 2008 and January 2009 and between August and December 2009.,Patients (one-81 years) with uncomplicated Plasmodium falciparum mono-infection were consecutively enrolled.,Follow-up visits were at day 2, 3, 7, 28 and 42 or any other day if symptoms reoccurred.,Primary and secondary endpoints were PCR-corrected and uncorrected cure rates (molecular differentiation between recrudescence and re-infection) on days 28 and 42.,Other secondary endpoints were gametocytaemia at day 7 and day 28, parasitaemia at day 2 and 3, and re-infection rates at day 28 and day 42.,Of 348 enrolled patients, 313 and 301 completed follow-up at day 28 and at day 42, respectively.,No early treatment failure occurred.,For per protocol analysis, PCR-uncorrected cure rates at day 28 and 42 were 99.1% (95% CI 98.0-100.0) and 91.1% (95% CI 87.9-94.3), respectively.,PCR-corrected cure rates at day 28 and 42 were 99.4% (95% CI 98.5-100.0) and 94.7% (95% CI 92.2-97.2), respectively.,PCR-corrected cure rate at day 42 for children ≤5 years was 90.6% (95% CI 82.4-98.7) only.,Adverse events were in general mild to moderate.,Incidence of new infections was 3.4% during 42 days, no new infections with Plasmodium vivax were observed.,Microscopically detected gametocytaemia was reduced by 80% between day 0 and day 7.,In general, AL was effective and well tolerated in Jimma Zone, Ethiopia.,However, the PCR-corrected recrudescence rate per-protocol at day 42 for children ≤5 years was 9.4%.,Therefore, further development should be monitored on a regular basis as recommended by WHO.

In 2005, the Ethiopian government launched a massive expansion of the malaria prevention and control programme.,The programme was aimed mainly at the reduction of malaria in populations living below 2,000 m above sea level.,Global warming has been implicated in the increase in the prevalence of malaria in the highlands.,However, there is still a paucity of information on the occurrence of malaria at higher altitudes.,The objective of this study was to estimate malaria prevalence in highland areas of south-central Ethiopia, designated as the Butajira area.,Using a multi-stage sampling technique, 750 households were selected.,All consenting family members were examined for malaria parasites in thick and thin blood smears.,The assessment was repeated six times for two years (October 2008 to June 2010).,In total, 19,207 persons were examined in the six surveys.,From those tested, 178 slides were positive for malaria, of which 154 (86.5%) were positive for Plasmodium vivax and 22 (12.4%) for Plasmodium falciparum; the remaining two (1.1%) showed mixed infections of Plasmodium falciparum and Plasmodium vivax.,The incidence of malaria was higher after the main rainy season, both in lower lying and in highland areas.,The incidence in the highlands was low and similar for all age groups, whereas in the lowlands, malaria occurred mostly in those of one to nine years of age.,This study documented a low prevalence of malaria that varied with season and altitudinal zone in a highland-fringe area of Ethiopia.,Most of the malaria infections were attributable to Plasmodium vivax.

Monocytes play an important role in the host defense against Plasmodium vivax as the main source of inflammatory cytokines and mitochondrial reactive oxygen species (mROS).,Here, we show that monocyte metabolism is altered during human P. vivax malaria, with mitochondria playing a major function in this switch.,The process involves a reprograming in which the cells increase glucose uptake and produce ATP via glycolysis instead of oxidative phosphorylation.,P. vivax infection results in dysregulated mitochondrial gene expression and in altered membrane potential leading to mROS increase rather than ATP production.,When monocytes were incubated with P. vivax-infected reticulocytes, mitochondria colocalized with phagolysosomes containing parasites representing an important source mROS.,Importantly, the mitochondrial enzyme superoxide dismutase 2 (SOD2) is simultaneously induced in monocytes from malaria patients.,Taken together, the monocyte metabolic reprograming with an increased mROS production may contribute to protective responses against P. vivax while triggering immunomodulatory mechanisms to circumvent tissue damage.

Tafenoquine (TQ) and primaquine (PQ) are 8-aminoquinolines (8-AQ) with anti-hypnozoite activity against vivax malaria.,PQ is the only FDA-approved medicine for preventing relapsing Plasmodium vivax infection and TQ is currently in phase 3 clinical trials for the same indication.,Recent studies have provided evidence that cytochrome P450 (CYP) metabolism via CYP2D6 plays a role in PQ efficacy against P. vivax and have suggested that this effect may extend to other 8-AQs, including TQ.,Here, a retrospective pharmacogenetic (PGx) investigation was performed to assess the impact of CYP2D6 metabolism on TQ and PQ efficacy in the treatment of P. vivax in the DETECTIVE study (TAF112582), a recently completed, randomized, phase 2b dose-ranging clinical trial.,The impact of CYP2D6 on TQ pharmacokinetics (PK) was also investigated in TAF112582 TQ-treated subjects and in vitro CYP metabolism of TQ was explored.,A limitation of the current study is that TAF112582 was not designed to be well powered for PGx, thus our findings are based on TQ or PQ efficacy in CYP2D6 intermediate metabolizers (IM), as there were insufficient poor metabolizers (PM) to draw any conclusion on the impact of the PM phenotype on efficacy.,The impact of genetically-predicted CYP2D6 reduced metabolism on relapse-free efficacy six months post-dosing of TQ or PQ, both administered in conjunction with chloroquine (CQ), was assessed using exact statistical methods in 198 P. vivax-infected study participants comparing IM to extensive metabolizers (EM).,The influence of CYP2D6 metabolizer phenotypes on TQ PK was assessed comparing median TQ area under the curve (AUC).,In vitro metabolism of TQ was investigated using recombinant, over-expressed human CYP enzymes and human hepatocytes.,Metabolite identification experiments were performed using liquid chromatography-mass spectrometry.,Reduction of CYP2D6 activity was not associated with an increase in relapse-rate in TQ-treated subjects (p = 0.57).,In contrast, and in accordance with recent literature, CYP2D6 IMs were more common (p = 0.05) in PQ-treated subjects who relapsed (50 %) than in subjects who remained relapse-free (17 %).,Further, CYP2D6 metabolizer phenotypes had no significant effect on TQ AUC, and only minimal metabolism of TQ could be detected in hepatic in vitro systems.,Together, these data provide preliminary evidence that in CYP2D6 IMs, TQ efficacy in P. vivax-infected individuals is not diminished to the same extent as PQ.,As there were no PMs in either the TQ or PQ treatment arms of TAF112582, no conclusions could be drawn on potential differences in PMs.,These findings suggest that differential effects of CYP2D6 metabolism on TQ and PQ efficacy could be a differentiation factor between these 8-AQs, but results remain to be confirmed prospectively in the ongoing phase 3 studies.,The online version of this article (doi:10.1186/s12936-016-1145-5) contains supplementary material, which is available to authorized users.

Malaria parasite prevalence in endemic populations is an essential indicator for monitoring the progress of malaria control, and has traditionally been assessed by microscopy.,However, surveys increasingly use sensitive molecular methods that detect higher numbers of infected individuals, questioning our understanding of the true infection burden and resources required to reduce it.,Here we analyse a series of data sets to characterize the distribution and epidemiological factors associated with low-density, submicroscopic infections.,We show that submicroscopic parasite carriage is common in adults, in low-endemic settings and in chronic infections.,We find a strong, non-linear relationship between microscopy and PCR prevalence in population surveys (n=106), and provide a tool to relate these measures.,When transmission reaches very low levels, submicroscopic carriers are estimated to be the source of 20-50% of all human-to-mosquito transmissions.,Our findings challenge the idea that individuals with little previous malaria exposure have insufficient immunity to control parasitaemia and suggest a role for molecular screening.,Malaria can persist at levels that escape detection by standard microscopy, but can be detected by PCR.,Okell et al. now show that rates of submicroscopic infection can be predicted using more widely available microscopy data, and are most epidemiologically significant in areas with low malaria transmission.

Submicroscopic malaria (SMM) can be defined as low-density infections of Plasmodium that are unlikely to be detected by conventional microscopy.,Such submicroscopic infections only occasionally cause acute disease, but they are capable of infecting mosquitoes and contributing to transmission.,This entity is frequent in endemic countries; however, little is known about imported SMM.,The goals of this study were two-fold: a) to know the frequency of imported SMM, and b) to describe epidemiological, laboratorial and clinical features of imported SMM.,A retrospective study based on review of medical records was performed.,The study population consisted of patients older than 15 years attended at the Tropical Medicine Unit of Hospital Carlos III, between January 1, 2002 and December 31, 2007.,Routinely detection techniques for Plasmodium included Field staining and microscopic examination through thick and thin blood smear.,A semi-nested multiplex malaria PCR was used to diagnose or to confirm cases with low parasitaemia.,SMM was diagnosed in 104 cases, representing 35.5% of all malaria cases.,Mean age (IC95%) was 40.38 years (37.41-43.34), and sex distribution was similar.,Most cases were in immigrants, but some cases were found in travellers.,Equatorial Guinea was the main country where infection was acquired (81.7%).,Symptoms were present only in 28.8% of all SMM cases, mainly asthenia (73.3% of symptomatic patients), fever (60%) and arthromialgias (53.3%).,The associated laboratory abnormalities were anaemia (27.9%), leukopaenia (15.4%) and thrombopaenia (15.4%).,Co-morbidity was described in 75 cases (72.1%).,Results from this study suggest that imported SMM should be considered in some patients attended at Tropical Medicine Units.,Although it is usually asymptomatic, it may be responsible of fever, or laboratory abnormalities in patients coming from endemic areas.,The possibility of transmission in SMM has been previously described in endemic zones, and presence of vector in Europe has also been reported.,Implementation of molecular tests in all asymptomatic individuals coming from endemic area is not economically feasible.,So re-emergence of malaria (Plasmodium vivax) in Europe may be speculated.

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

Artemether/lumefantrine (Coartem®) has been used as a treatment for uncomplicated Plasmodium falciparum infection since 2004 in Benin.,This open-label, non-randomized study evaluated efficacy of artemether-lumefantrine (AL) in treatment of uncomplicated falciparum malaria in children aged 6-59 months in two malaria transmission sites in northwest Benin.,A 42-day therapeutic efficacy study was conducted between August and November 2014, in accordance with 2009 WHO guidelines.,One-hundred and twenty-three children, aged 6 months to 5 years, with uncomplicated falciparum malaria were recruited into the study.,The primary endpoint was parasitological cure on day 28 and day 42 while the secondary endpoints included: parasite and fever clearance, improvement in haemoglobin levels.,Outcomes were classified as early treatment failure (ETF), late clinical failure, late parasitological failure, and adequate clinical and parasitological response (ACPR).,Before PCR correction, ACPR rates were 87 % (95 % CI 76.0-94.7) and 75.6 %, respectively (95 % CI 67.0-82.9) on day 28 and day 42.,In each study site, ACPR rates were 78.3 % in Djougou and 73 % in Cobly on day 42.,There was no ETF and after PCR correction ACPR was 100 % in study population.,All treatment failures were shown to be due to new infections.,Fever was significantly cleared in 24 h and approximately 90 % of parasites where cleared on day 1 and almost all parasites were cleared on day 2.,Haemoglobin concentration showed a slight increase with parasitic clearance.,AL remains an efficacious drug for the treatment of uncomplicated falciparum malaria in Benin, although higher rates of re-infection remain a concern.,Surveillance needs to be continued to detect future changes in parasite sensitivity to artemisinin-based combination therapy.

This study identified CD16+ DCs as the only blood DC subset distinctively activated during primary blood-stage human Plasmodium infection.,As TNF/IL-10 coproducers, CD16+ DCs contribute to early inflammatory processes, yet P falciparum restimulation skewed cytokine responses further towards IL-10 production.,The malaria causing parasite Plasmodium subverts host immune responses by several strategies including the modulation of dendritic cells (DCs).,In this study, we show that Plasmodium falciparum skewed CD16+ DC cytokine responses towards interleukin (IL)-10 production in vitro, distinct to the cytokine profile induced by Toll-like receptor ligation.,To determine CD16+ DC responsiveness in vivo, we assessed their function after induced P falciparum infection in malaria-naive volunteers.,CD16+ DCs underwent distinctive activation, with increased expression of maturation markers human leukocyte antigen (HLA)-DR and CD86, enhanced tumor necrosis factor (TNF) production, and coproduction of TNF/IL-10.,In vitro restimulation with P falciparum further increased IL-10 production.,In contrast, during naturally acquired malaria episode, CD16+ DCs showed diminished maturation, suggesting increased parasite burden and previous exposure influence DC subset function.,These findings identify CD16+ DCs as the only DC subset activated during primary blood-stage human Plasmodium infection.,As dual cytokine producers, CD16+ DCs contribute to inflammatory as well as regulatory innate immune processes.

An understanding of the mechanisms mediating protective immunity against malaria in humans is currently lacking, but critically important to advance the development of highly efficacious vaccines.,Antibodies play a key role in acquired immunity, but the functional basis for their protective effect remains unclear.,Furthermore, there is a strong need for immune correlates of protection against malaria to guide vaccine development.,Using a validated assay to measure opsonic phagocytosis of Plasmodium falciparum merozoites, we investigated the potential role of this functional activity in human immunity against clinical episodes of malaria in two independent cohorts (n = 109 and n = 287) experiencing differing levels of malaria transmission and evaluated its potential as a correlate of protection.,Antibodies promoting opsonic phagocytosis of merozoites were cytophilic immunoglobulins (IgG1 and IgG3), induced monocyte activation and production of pro-inflammatory cytokines, and were directed against major merozoite surface proteins (MSPs).,Consistent with protective immunity in humans, opsonizing antibodies were acquired with increasing age and malaria exposure, were boosted on re-infection, and levels were related to malaria transmission intensity.,Opsonic phagocytosis was strongly associated with a reduced risk of clinical malaria in longitudinal studies in children with current or recent infections.,In contrast, antibodies to the merozoite surface in standard immunoassays, or growth-inhibitory antibodies, were not significantly associated with protection.,In multivariate analyses including several antibody responses, opsonic phagocytosis remained significantly associated with protection against malaria, highlighting its potential as a correlate of immunity.,Furthermore, we demonstrate that human antibodies against MSP2 and MSP3 that are strongly associated with protection in this population are effective in opsonic phagocytosis of merozoites, providing a functional link between these antigen-specific responses and protection for the first time.,Opsonic phagocytosis of merozoites appears to be an important mechanism contributing to protective immunity in humans.,The opsonic phagocytosis assay appears to be a strong correlate of protection against malaria, a valuable biomarker of immunity, and provides a much-needed new tool for assessing responses to blood-stage malaria vaccines and measuring immunity in populations.

Systematic non-compliance to chemotherapeutic treatment among a portion of the eligible population is thought to be a major obstacle to the elimination of helminth infections by mass drug administration (MDA).,MDA for helminths is repeated at defined intervals such as yearly or every 2 years, as a consequence of the inability of the human host to develop fully protective immunity to reinfection.,As such, how an individual complies to these repeated rounds of MDA can have a significant impact on parasite transmission.,The importance of this factor is poorly understood at present.,Few epidemiological studies have examined longitudinal trends in compliance in the many communities in areas of endemic helminth infection that are undergoing MDA.,Reducing systematic non-compliance will obviously increase the number of individuals treated, but it may also alter the dynamics of parasite transmission.,Here we develop an individual-based stochastic model of helminth transmission and MDA treatment to investigate how different patterns of compliance influence the impact of MDA for two groups of helminths, the soil transmitted nematode infections and the schistosome parasites.,We study the effect of several alternative treatment and compliance patterns on the dynamics of transmission.,We find that the impact of different compliance patterns, ranging from random treatment at each round of chemotherapy to systematic non-compliance by a proportion of the population, is very dependent on both transmission intensity in a defined setting and the type of infection that the treatment is targeted at.,Systematic non-compliance has a greater impact on the potential for elimination of Schistosoma mansoni transmission by intensive MDA, than it does on Ascaris lumbricoides.,We discuss the implications of our findings for the prioritisation of resources in MDA programmes and for monitoring and evaluation programme design.,The key message generated by the analyses is that great care must be taken to record individual longitudinal patterns of compliance at each round of MDA as opposed to just recording overall coverage.,The online version of this article (doi:10.1186/s13071-017-2206-5) contains supplementary material, which is available to authorized users.

We tracked individuals during mass drug administration.,Untreated individuals were not hard to reach for local drug distributors and would comply with treatment if offered.,Household socioeconomic status and minority group affiliation identified untreated individuals; infection risk factors were not predictive of drug receipt.,Background.,Repeated mass drug administration (MDA) with preventive chemotherapies is the mainstay of morbidity control for schistosomiasis and soil-transmitted helminths, yet the World Health Organization recently reported that less than one-third of individuals who required preventive chemotherapies received treatment.,Methods.,Coverage of community-directed treatment with praziquantel (PZQ) and albendazole (ALB) was analyzed in 17 villages of Mayuge District, Uganda.,National drug registers, household questionnaires, and parasitological surveys were collected to track 935 individuals before and after MDA.,Multilevel logistic regressions, including household and village effects, were specified with a comprehensive set of socioeconomic and parasitological variables.,The factors predicting who did not receive PZQ and ALB from community medicine distributors were identified.,Results.,Drug receipt was correlated among members within a household, and nonrecipients of PZQ or ALB were profiled by household-level socioeconomic factors.,Individuals were less likely to receive either PZQ or ALB if they had a Muslim household head or low home quality, belonged to the minority tribe, or had settled for more years in their village.,Untreated individuals were also more likely to belong to households that did not purify drinking water, had no home latrine, and had no members who were part of the village government.,Conclusions.,The findings demonstrate how to locate and target individuals who are not treated in MDA.,Infection risk factors were not informative.,In particular, age, gender, and occupation were unable to identify non-recipients, although World Health Organization guidelines rely on these factors.,Individuals of low socioeconomic status, minority religions, and minority tribes can be targeted to expand MDA coverage.

Although malaria remains a noteworthy disease in South Africa, the provinces are at differing stages of the malaria elimination continuum.,KwaZulu-Natal has consistently reported the lowest number of cases over the past 5 years and it is expected that the goal of elimination will be achieved in this province over the next few years.,The study reports on few key indicators that realistically represents the provinces progress over the past decade.,Local and imported morbidity and mortality is seen as the key indicator as is malaria in children under the age of five and pregnant women.,The only vector control intervention in the province is indoor residual spraying (IRS) and this gives an estimate of the population protected by this intervention.,Trend analysis was used to examine the changing epidemiology in KwaZulu-Natal over the past decade from 2008 to 2018.,The data used in this decadal analysis was obtained from the provincial Department of Health.,Since malaria is a medically notifiable disease, all malaria cases diagnosed in the province are reported from health facilities and are captured in the malaria information system in the province.,The results have shown that imported cases are on the increase whilst local cases are decreasing, in keeping with an elimination objective.,Preventing secondary cases is the key to reaching elimination.,Only 10% of the cases reported occur in children under 5 years whereas the cases in pregnant women account for about 1% of the reported cases.,Over 85% of the houses receive IRS and this is also the same proportion of the population protected by the intervention.,Several challenges to elimination have been identified but these are not insurmountable.,Although there are major impediments to achieving elimination, the changing epidemiology suggests that major strides have been made in the past 10 years and KwaZulu-Natal is on track to achieving this milestone in the next few years.

South Africa is one of many countries committed to malaria elimination with a target of 2018 and all malaria-endemic provinces, including Mpumalanga, are increasing efforts towards this ambitious goal.,The reduction of imported infections is a vital element of an elimination strategy, particularly if a country is already experiencing high levels of imported infections.,Border control of malaria is one tool that may be considered.,A metapopulation, non-linear stochastic ordinary differential equation model is used to simulate malaria transmission in Mpumalanga and Maputo province, Mozambique (the source of the majority of imported infections) to predict the impact of a focal screen and treat campaign at the Mpumalanga-Maputo border.,This campaign is simulated by nesting an individual-based model for the focal screen and treat campaign within the metapopulation transmission model.,The model predicts that such a campaign, simulated for different levels of resources, coverage and take-up rates with a variety of screening tools, will not eliminate malaria on its own, but will reduce transmission substantially.,Making the campaign mandatory decreases transmission further though sub-patent infections are likely to remain undetected if the diagnostic tool is not adequately sensitive.,Replacing screening and treating with mass drug administration results in substantially larger decreases as all (including sub-patent) infections are treated before movement into Mpumalanga.,The reduction of imported cases will be vital to any future malaria control or elimination strategy.,This simulation predicts that FSAT at the Mpumalanga-Maputo border will be unable to eliminate local malaria on its own, but may still play a key role in detecting and treating imported infections before they enter the country.,Thus FSAT may form part of an integrated elimination strategy where a variety of interventions are employed together to achieve malaria elimination.,The online version of this article (doi:10.1186/s12936-015-0776-2) contains supplementary material, which is available to authorized users.

Carriage and density of gametocytes, the transmission stages of malaria parasites, are determined for predicting the infectiousness of humans to mosquitoes.,This measure is used for evaluating interventions that aim at reducing malaria transmission.,Gametocytes need to be detected by amplification of stage-specific transcripts, which requires RNA-preserving blood sampling.,For simultaneous, highly sensitive quantification of both, blood stages and gametocytes, we have compared and optimized different strategies for field and laboratory procedures in a cross sectional survey in 315 5-9 yr old children from Papua New Guinea. qRT-PCR was performed for gametocyte markers pfs25 and pvs25, Plasmodium species prevalence was determined by targeting both, 18S rRNA genes and transcripts.,RNA-based parasite detection resulted in a P. falciparum positivity of 24.1%; of these 40.8% carried gametocytes.,P. vivax positivity was 38.4%, with 38.0% of these carrying gametocytes.,Sensitivity of DNA-based parasite detection was substantially lower with 14.1% for P. falciparum and 19.6% for P. vivax.,Using the lower DNA-based prevalence of asexual stages as a denominator increased the percentage of gametocyte-positive infections to 59.1% for P. falciparum and 52.4% for P. vivax.,For studies requiring highly sensitive and simultaneous quantification of sexual and asexual parasite stages, 18S rRNA transcript-based detection saves efforts and costs.,RNA-based positivity is considerably higher than other methods.,On the other hand, DNA-based parasite quantification is robust and permits comparison with other globally generated molecular prevalence data.,Molecular monitoring of low density asexual and sexual parasitaemia will support the evaluation of effects of up-scaled antimalarial intervention programs and can also inform about small scale spatial variability in transmission intensity.

To prepare field sites for malaria vaccine trials, it is important to determine baseline antibody and T cell responses to candidate malaria vaccine antigens.,Assessing T cell responses is especially challenging, given genetic restriction, low responses observed in endemic areas, their variability over time, potential suppression by parasitaemia and the intrinsic variability of the assays.,In Part A of this study, antibody titres were measured in adults from urban and rural communities in Ghana to recombinant Plasmodium falciparum CSP, SSP2/TRAP, LSA1, EXP1, MSP1, MSP3 and EBA175 by ELISA, and to sporozoites and infected erythrocytes by IFA.,Positive ELISA responses were determined using two methods.,T cell responses to defined CD8 or CD4 T cell epitopes from CSP, SSP2/TRAP, LSA1 and EXP1 were measured by ex vivo IFN-γ ELISpot assays using HLA-matched Class I- and DR-restricted synthetic peptides.,In Part B, the reproducibility of the ELISpot assay to CSP and AMA1 was measured by repeating assays of individual samples using peptide pools and low, medium or high stringency criteria for defining positive responses, and by comparing samples collected two weeks apart.,In Part A, positive antibody responses varied widely from 17%-100%, according to the antigen and statistical method, with blood stage antigens showing more frequent and higher magnitude responses.,ELISA titres were higher in rural subjects, while IFA titres and the frequencies and magnitudes of ex vivo ELISpot activities were similar in both communities.,DR-restricted peptides showed stronger responses than Class I-restricted peptides.,In Part B, the most stringent statistical criteria gave the fewest, and the least stringent the most positive responses, with reproducibility slightly higher using the least stringent method when assays were repeated.,Results varied significantly between the two-week time-points for many participants.,All participants were positive for at least one malaria protein by ELISA, with results dependent on the criteria for positivity.,Likewise, ELISpot responses varied among participants, but were relatively reproducible by the three methods tested, especially the least stringent, when assays were repeated.,However, results often differed between samples taken two weeks apart, indicating significant biological variability over short intervals.

Two blinded, controlled laboratory studies were conducted to assess the acaricidal efficacy of a new combination of fipronil and permethrin (Frontline Tri-Act®/Frontect®) against two tick species.,Study A evaluated the efficacy of the product against both Ixodes ricinus and Rhipicephalus sanguineus and Study B evaluated the efficacy against R. sanguineus only.,16 (Study A) and 12 (Study B) healthy adult dogs were allocated to two groups in each study.,Dogs in Group 1 served as untreated controls.,Dogs in Group 2 were treated with a new topical spot-on formulation containing 6.76% (w/v) fipronil + 50.48% (w/v) permethrin once on Day 0.,Each dog of study A was infested with 50 unfed adult ticks of each species and each dog of study B was infested with 50 unfed adult Rhipicephalus sanguineus prior to treatment (Day −2 in Study A, Day −1 in Study B) and post treatment on Days 7, 14, 21 and 28.,The ticks were removed and counted 48 h after treatment (Day 2) or subsequent infestations (Days 9, 16, 23 and 30).,Acaricidal efficacy was defined as the percent reduction in the number of live ticks in the treated group compared to the untreated control group.,The percent efficacy in the treated group for R. sanguineus was 100%, 100%, 100%, 100% and 96.7% in Study A, and 94.4%, 100%, 100%, 98.7% and 98.0% in Study B, for counts performed on Days 2, 9, 16, 23 and 30, respectively.,For I. ricinus, in Study A, the percent efficacy of the treatment was 100%, 100%, 100%, 100% and 99.2% for counts performed on Days 2, 9, 16, 23 and 30, respectively.,There was a significant difference of the geometric mean numbers of live ticks between the treated and control groups at each time point in each study (p = 0.005 for every day in Study A, and p < 0.005 for every day in Study B).,A single topical administration of a combination of fipronil and permethrin provides excellent acaricidal efficacy against both I. ricinus and R. sanguineus for at least 4 weeks.

The capacity of a topical combination of imidacloprid and permethrin (Advantix®) to prevent transmission of Ehrlichia canis was studied in two groups of six dogs.,One group served as controls, whereas the other group was treated.,All dogs were exposed to E. canis-infected Rhipicephalus sanguineus ticks on Days 7, 14, 21 and Day 28 post acaricidal treatment.,The adult R. sanguineus ticks were released into the individual kennels of the dogs to simulate natural tick exposure.,In situ tick counts were conducted on Day 9, 16 and 23 and any remaining ticks were counted and removed on Day 30.,The efficacy of the acaricidal treatment against R. sanguineus ranged between 96.1% and 98.9% at 48 h post-application and lasted up to 4 weeks.,Four out of six control dogs became infected with E. canis, as demonstrated by the presence of specific E. canis antibodies and the detection by PCR of E. canis DNA in blood samples.,These dogs became thrombocytopenic and displayed fever and were consecutively rescue-treated by doxycycline.,None of the six treated dogs became infected with E. canis, as confirmed by the lack of specific antibodies and absence of E. canis DNA in blood samples.,Advantix® prevented transmission of E. canis and provided protection against monocytic ehrlichiosis for 4 weeks post acaricidal treatment.

Populations within schistosomiasis control areas, especially those in Africa, are recommended to receive regular mass drug administration (MDA) with praziquantel (PZQ) as the main strategy for controlling the disease.,The impact of PZQ treatment on schistosome genetics remains poorly understood, and is limited by a lack of high-resolution genetic data on the population structure of parasites within these control areas.,We generated whole-genome sequence data from 174 individual miracidia collected from both children and adults from fishing communities on islands in Lake Victoria in Uganda that had received either annual or quarterly MDA with PZQ over four years, including samples collected immediately before and four weeks after treatment.,Genome variation within and between samples was characterised and we investigated genomic signatures of natural selection acting on these populations that could be due to PZQ treatment.,The parasite population on these islands was more diverse than found in nearby villages on the lake shore.,We saw little or no genetic differentiation between villages, or between the groups of villages with different treatment intensity, but slightly higher genetic diversity within the pre-treatment compared to post-treatment parasite populations.,We identified classes of genes significantly enriched within regions of the genome with evidence of recent positive selection among post-treatment and intensively treated parasite populations.,The differential selection observed in post-treatment and pre-treatment parasite populations could be linked to any reduced susceptibility of parasites to praziquantel treatment.

Urbanization is increasing across the globe, and diseases once considered rural can now be found in urban areas due to the migration of populations from rural endemic areas, local transmission within the city, or a combination of factors.,We investigated the epidemiologic characteristics of urban immigrants and natives living in a neighborhood of Salvador, Brazil where there is a focus of transmission of Schistosoma mansoni.,In a cross-sectional study, all inhabitants from 3 sections of the community were interviewed and examined.,In order to determine the degree of parasite differentiation between immigrants and the native born, S. mansoni eggs from stools were genotyped for 15 microsatellite markers.,The area received migrants from all over the state, but most infected children had never been outside of the city, and infected snails were present at water contact sites.,Other epidemiologic features suggested immigration contributed little to the presence of infection.,The intensity and prevalence of infection were the same for immigrants and natives when adjusted for age, and length of immigrant residence in the community was positively associated with prevalence of infection.,The population structure of the parasites also supported that the contribution from immigration was small, since the host-to-host differentiation was no greater in the urban parasite population than a rural population with little distant immigration, and there had been little differentiation in the urban population over the past 7 years.,Public health efforts should focus on eliminating local transmission, and once eliminated, reintroduction from distant migration is unlikely.

Safety and efficacy of primaquine against repeated attacks of Plasmodium vivax depends upon co-administered blood schizontocidal therapy in radical cure.,We assessed primaquine (PQ) as hypnozoitocide when administered with dihydroartemisinin-piperaquine (Eurartesim®, DHA-PP) or artesunate-pyronaridine (Pyramax®, AS-PYR) to affirm its good tolerability and efficacy.,A third arm, artesunate followed by primaquine, was not intended as therapy for practice, but addressed a hypothesis concerning primaquine efficacy without co-administration of blood schizontocide.,During March to July 2013, an open-label, randomized trial enrolled Indonesian soldiers with vivax malaria at Sragen, Central Java, after six months duty in malarious Papua, Indonesia.,No malaria transmission occurred at the study site and P. vivax recurrences in the 12 months following therapy were classified as relapses.,A historic relapse control derived from a cohort of soldiers who served in the same area of Papua was applied to estimate risk of relapse among randomized treatment groups.,Those were: 1) AS followed 2d later by PQ (0.5 mg/kg daily for 14d); 2) co-formulated AS-PYR concurrent with the same regimen of PQ; or 3) co-formulated DHA-PP concurrent with the same regimen of PQ.,Among 532 soldiers, 219 had vivax malaria during the four months following repatriation to Java; 180 of these were otherwise healthy and G6PD-normal and enrolled in the trial.,Subjects in all treatment groups tolerated the therapies well without untoward events and cleared parasitemia within three days.,First relapse appeared at day 39 post-enrollment, and the last at day 270.,Therapeutic efficacy of PQ against relapse by incidence density analysis was 92 % (95 %CI = 83-97 %), 94 %(95 %CI = 86-97 %), and 95 %(95 %CI = 88-98 %) when combined with AS, AS-PYR, or DHA-PP, respectively.,This trial offers evidence of good tolerability and efficacy of PQ against P. vivax relapse when administered concurrently with DHA-PP or AS-PYR.,These offer alternative partner drugs for radical cure with primaquine.,The AS arm demonstrated efficacy with a total dose of 7 mg/kg PQ without concurrently administered blood schizontocide, another option when primaquine therapy is removed in time from the treatment of the acute malaria or applied presumptively without an attack.,Current Controlled Trials ISRCTN82366390, assigned 20 March 2013.

Background.,A high prevalence of chloroquine-resistant Plasmodium vivax in Indonesia has shifted first-line treatment to artemisinin-based combination therapies, combined with primaquine (PQ) for radical cure.,Which combination is most effective and safe remains to be established.,Methods.,We conducted a prospective open-label randomized comparison of 14 days of PQ (0.25 mg base/kg) plus either artesunate-amodiaquine (AAQ + PQ) or dihydroartemisinin-piperaquine (DHP + PQ) for the treatment of uncomplicated monoinfection P. vivax malaria in North Sumatera, Indonesia.,Patients were randomized and treatments were given without prior testing for G6PD status.,The primary outcome was parasitological failure at day 42.,Patients were followed up to 1 year.,Results.,Between December 2010 and April 2012, 331 patients were included.,After treatment with AAQ + PQ, recurrent infection occurred in 0 of 167 patients within 42 days and in 15 of 130 (11.5%; 95% confidence interval [CI], 6.6%-18.3%) within a year.,With DHP + PQ, this was 1 of 164 (0.6%; 95% CI, 0.01%-3.4%) and 13 of 143 (9.1%; 95% CI, 4.9%-15.0%), respectively (P > .2).,Intravascular hemolysis occurred in 5 patients, of which 3 males were hemizygous for the G6PD-Mahidol mutation.,Minor adverse events were more frequent with AAQ + PQ.,Conclusions.,In North Sumatera, Indonesia, AAQ and DHP, both combined with PQ, were effective for blood-stage parasite clearance of uncomplicated P. vivax malaria.,Both treatments were safe, but DHP + PQ was better tolerated.,Clinical Trials Registration.,NCT01288820.

Tanzania has seen a reduction in the fraction of fevers caused by malaria, likely due in part to scale-up of control measures.,While national guidelines require parasite-based diagnosis prior to treatment, it is estimated that more than half of suspected malaria treatment-seeking in Tanzania initiates in the private retail sector, where diagnosis by malaria rapid diagnostic test (RDT) or microscopy is illegal.,This pilot study investigated whether the introduction of RDTs into Accredited Drug Dispensing Outlets (ADDOs) under realistic market conditions would improve case management practices.,Dispensers from ADDOs in two intervention districts in Tanzania were trained to stock and perform RDTs and monitored quarterly.,Each district was assigned a different recommended retail price to evaluate the need for a subsidy.,Malaria RDT and artemisinin-based combination therapy (ACT) uptake and availability were measured pre-intervention and 1 year post-intervention through structured surveys of ADDO owners and exiting customers in both intervention districts and one contiguous control district.,Descriptive analysis and logistic regression were used to compare the three districts and identify predictive variables for testing.,A total of 310 dispensers from 262 ADDOs were trained to stock and perform RDTs.,RDT availability in intervention ADDOs increased from 1% (n = 172) to 73% (n = 163) during the study; ACT medicines were available in 75% of 260 pre-intervention and 68% of 254 post-intervention ADDOs.,Pre-treatment testing performed within the ADDO increased from 0 to 65% of suspected malaria patients who visited a shop (95% CI 60.8-69.6%) with no difference between intervention districts.,Overall parasite-based diagnosis increased from 19 to 74% in intervention districts and from 3 to 18% in the control district.,Prior knowledge of RDT availability (aOR = 1.9, p = 0.03) and RDT experience (aOR = 1.9, p = 0.01) were predictors for testing.,Adherence data indicated that 75% of malaria positives received ACT, while 3% of negatives received ACT.,Trained and supervised ADDO dispensers in rural Tanzania performed and sold RDTs under real market conditions to two-thirds of suspected malaria patients during this one-year pilot.,These results support the hypothesis that introducing RDTs into regulated private retail sector settings can improve malaria testing and treatment practices without an RDT subsidy.,Trial registration ISRCTN ISRCTN14115509

The success of community case management in improving access to effective malaria treatment for young children relies on broad utilization of community health workers (CHWs) to diagnose and treat fever cases.,A better understanding of the factors associated with CHW utilization is crucial in informing national malaria control policy and strategy in Kenya.,Specifically, little is known in Kenya on the extent to which CHWs are utilized, the characteristics of families who report utilizing CHWs and whether utilization is associated with improved access to prompt and effective malaria treatment.,This paper examines factors associated with utilization of CHWs in improving access to malaria treatment among children under five years of age by women caregivers in two malaria endemic districts in Kenya.,This study was conducted in 113 hard-to-reach and poor villages in Malindi and Lamu districts in the coastal region classified as having endemic transmission of malaria.,A cross-sectional household survey was conducted using a standardized malaria indicator questionnaire at baseline (n = 1,187) and one year later at endline assessment (n = 1,374) using two-stage cluster sampling.,There was an increase in reported utilization of CHWs as source of advice/treatment for child fevers from 2% at baseline to 35% at endline, accompanied by a decline in care-seeking from government facilities (from 67% to 48%) and other sources (26% to 2%) including shops.,The most poor households and poor households reported higher utilization of CHWs at 39.4% and 37.9% respectively, compared to the least poor households (17.0%).,Households in villages with less than 200 households reported higher CHWs utilization as compared to households in villages having >200 households.,Prompt access to timely and effective treatment was 5.7 times higher (95% CI 3.4-9.7) when CHWs were the source of care sought.,Adherence was high regardless of whether source was CHWs (73.1%) or public health facility (66.7%).,The potential for utilization of CHWs in improving access to malaria treatment at the community level is promising.,This will not only enhance access to treatment by the poorest households but also provide early and appropriate treatment to vulnerable individuals, especially those living in hard to reach areas.

Recent global progress in scaling up malaria control interventions has revived the goal of complete elimination in many countries.,Decreasing transmission intensity generally leads to increasingly patchy spatial patterns of malaria transmission in elimination settings, with control programs having to accurately identify remaining foci in order to efficiently target interventions.,The role of connectivity between different pockets of local transmission is of increasing importance as programs near elimination since humans are able to transfer parasites beyond the limits of mosquito dispersal, thus re-introducing parasites to previously malaria-free regions.,Here, we discuss recent advances in the quantification of spatial epidemiology of malaria, particularly Plasmodium falciparum, in the context of transmission reduction interventions.,Further, we highlight the challenges and promising directions for the development of integrated mapping, modeling, and genomic approaches that leverage disparate datasets to measure both connectivity and transmission.,A more comprehensive understanding of the spatial transmission of malaria can be gained using a combination of parasite genetics and epidemiological modeling and mapping.,However, additional molecular and quantitative methods are necessary to answer these public health-related questions.

Malaria re-introduction is a challenge in elimination settings.,To prevent re-introduction, receptivity, vulnerability, and health system capacity of foci should be monitored using appropriate tools.,This study aimed to design an applicable model to monitor predicting factors of re-introduction of malaria in highly prone areas.,This exploratory, descriptive study was conducted in a pre-elimination setting with a high-risk of malaria transmission re-introduction.,By using nominal group technique and literature review, a list of predicting indicators for malaria re-introduction and outbreak was defined.,Accordingly, a checklist was developed and completed in the field for foci affected by re-introduction and for cleared-up foci as a control group, for a period of 12 weeks before re-introduction and for the same period in the previous year.,Using field data and analytic hierarchical process (AHP), each variable and its sub-categories were weighted, and by calculating geometric means for each sub-category, score of corresponding cells of interaction matrices, lower and upper threshold of different risks strata, including low and mild risk of re-introduction and moderate and high risk of malaria outbreaks, were determined.,The developed predictive model was calibrated through resampling with different sets of explanatory variables using R software.,Sensitivity and specificity of the model were calculated based on new samples.,Twenty explanatory predictive variables of malaria re-introduction were identified and a predictive model was developed.,Unpermitted immigrants from endemic neighbouring countries were determined as a pivotal factor (AHP score: 0.181).,Moreover, quality of population movement (0.114), following malaria transmission season (0.088), average daily minimum temperature in the previous 8 weeks (0.062), an outdoor resting shelter for vectors (0.045), and rainfall (0.042) were determined.,Positive and negative predictive values of the model were 81.8 and 100 %, respectively.,This study introduced a new, simple, yet reliable model to forecast malaria re-introduction and outbreaks eight weeks in advance in pre-elimination and elimination settings.,The model incorporates comprehensive deterministic factors that can easily be measured in the field, thereby facilitating preventive measures.,The online version of this article (doi:10.1186/s12936-016-1192-y) contains supplementary material, which is available to authorized users.

Human echinococcosis is a neglected zoonosis caused by parasites of the genus Echinococcus.,The most frequent clinical forms of echinococcosis, cystic echinococcosis (CE) and alveolar echinococcosis (AE), are responsible for a substantial health and economic burden, particularly to low-income societies.,Quantitative epidemiology can provide important information to improve the understanding of parasite transmission and hence is an important part of efforts to control this disease.,The purpose of this review is to give an insight on factors associated with echinococcosis in animal hosts by summarising significant results reported from epidemiological studies identified through a systematic search.,The systematic search was conducted mainly in electronic databases but a few additional records were obtained from other sources.,Retrieved entries were examined in order to identify available peer-reviewed epidemiological studies that found significant risk factors for infection using associative statistical methods.,One hundred studies met the eligibility criteria and were suitable for data extraction.,Epidemiological factors associated with increased risk of E. granulosus infection in dogs included feeding with raw viscera, possibility of scavenging dead animals, lack of anthelmintic treatment and owners' poor health education and indicators of poverty.,Key factors associated with E. granulosus infection in intermediate hosts were related to the hosts' age and the intensity of environmental contamination with parasite eggs.,E. multilocularis transmission dynamics in animal hosts depended on the interaction of several ecological factors, such as hosts' population densities, host-prey interactions, landscape characteristics, climate conditions and human-related activities.,Results derived from epidemiological studies provide a better understanding of the behavioural, biological and ecological factors involved in the transmission of this parasite and hence can aid in the design of more effective control strategies.

Austria is part of the classical area of central Europe to which alveolar echinococcosis (AE) is endemic.,Annual incidences in Austria were 2.4 and 2.8 cases/100,000 population during 1991-2000 and 2001-2010, respectively.,Hence, the registration of 13 new AE patients in 2011 was unexpected.,Increasing fox populations and past AE underreporting might have caused this increase.

Zoonotic enteric parasites are ubiquitous and remain a public health threat to humans due to our close relationship with domestic animals and wildlife, inadequate water, sanitation, and hygiene practices and diet.,While most communities are now sedentary, nomadic and pastoral populations still exist and experience unique exposure risks for acquiring zoonotic enteric parasites.,Through this systematic review we sought to summarize published research regarding pathogens present in nomadic populations and to identify the risk factors for their infection.,Using systematic review guidelines set forth by PRISMA, research articles were identified, screened and summarized based on exclusion criteria for the documented presence of zoonotic enteric parasites within nomadic or pastoral human populations.,A total of 54 articles published between 1956 and 2016 were reviewed to determine the pathogens and exposure risks associated with the global transhumance lifestyle.,The included articles reported more than twenty different zoonotic enteric parasite species and illustrated several risk factors for nomadic and pastoralist populations to acquire infection including; a) animal contact, b) food preparation and diet, and c) household characteristics.,The most common parasite studied was Echinococcosis spp. and contact with dogs was recognized as a leading risk factor for zoonotic enteric parasites followed by contact with livestock and/or wildlife, water, sanitation, and hygiene barriers, home slaughter of animals, environmental water exposures, household member age and sex, and consumption of unwashed produce or raw, unprocessed, or undercooked milk or meat.,Nomadic and pastoral communities are at risk of infection with a variety of zoonotic enteric parasites due to their living environment, cultural and dietary traditions, and close relationship to animals.,Global health efforts aimed at reducing the transmission of these animal-to-human pathogens must incorporate a One Health approach to support water, sanitation, and hygiene development, provide education on safe food handling and preparation, and improve the health of domestic animals associated with these groups, particularly dogs.

Previous research on trichinellosis in Africa focused on isolating Trichinella from wildlife while the role of domestic pigs has remained highly under-researched.,Pig keeping in Uganda is historically recent, and evidence on zoonotic pig diseases, including infection with Trichinella species, is scarce.,A cross-sectional survey on Trichinella seroprevalence in pigs was conducted in three districts in Central and Eastern Uganda from April 2013 to January 2015.,Serum from a random sample of 1125 pigs from 22 villages in Eastern and Central Uganda was examined to detect immunoglobulin G (IgG) against any Trichinella spp. using a commercially available ELISA based on excretory-secretory antigen.,ELISA positive samples were confirmed using Western Blot based on somatic antigen of Trichinella spiralis as recommended in previous validation studies.,Diaphragm pillar muscle samples (at least 5 g each) of 499 pigs from areas with high ELISA positivity were examined using the artificial digestion method.,Overall, 78 of all 1125 animals (6.9%, 95% CI: 5.6-8.6%) tested positive for antibodies against Trichinella spp. in the ELISA at significantly higher levels in Kamuli district compared to Masaka and Mukono districts.,Thirty-one percent of the ELISA positive samples were confirmed IgG positive by the Western Blot leading to an overall seroprevalence of 2.1% (95% CI: 1.4-3.2%).,The large proportion of ELISA positive samples that could not be confirmed using Western blot may be the result of cross-reactivity with other gastrointestinal helminth infections or unknown host-specific immune response mechanisms in local pig breeds in Uganda.,Attempts to isolate muscle larvae for species determination using the artificial digestion method were unsuccessful.,Due to the large number of muscle samples examined we are confident that even if pigs are infected, the larval burden in pork is too low to pose a major risk to consumers of developing trichinellosis.,This was the first large systematic field investigation of Trichinella infection in domestic pigs in Uganda and its results imply that further studies are needed to identify the Trichinella species involved, and to identify potential sources of infection for humans.

Mapping malaria risk is an integral component of efficient resource allocation.,Routine health facility data are convenient to collect, but without information on the locations at which transmission occurred, their utility for predicting variation in risk at a sub-catchment level is presently unclear.,Using routinely collected health facility level case data in Swaziland between 2011-2013, and fine scale environmental and ecological variables, this study explores the use of a hierarchical Bayesian modelling framework for downscaling risk maps from health facility catchment level to a fine scale (1 km x 1 km).,Fine scale predictions were validated using known household locations of cases and a random sample of points to act as pseudo-controls.,Results show that fine-scale predictions were able to discriminate between cases and pseudo-controls with an AUC value of 0.84.,When scaled up to catchment level, predicted numbers of cases per health facility showed broad correspondence with observed numbers of cases with little bias, with 84 of the 101 health facilities with zero cases correctly predicted as having zero cases.,This method holds promise for helping countries in pre-elimination and elimination stages use health facility level data to produce accurate risk maps at finer scales.,Further validation in other transmission settings and an evaluation of the operational value of the approach is necessary.,The online version of this article (doi:10.1186/1475-2875-13-421) contains supplementary material, which is available to authorized users.

The past century has seen a significant contraction in the global extent of malaria transmission, resulting in over 50 countries being declared malaria free, and many regions of currently endemic countries eliminating the disease.,Moreover, substantial reductions in transmission have been seen since 1900 in those areas that remain endemic today.,Recent work showed that this malaria recession was unlikely to have been driven by climatic factors, and that control measures likely played a significant role.,It has long been considered, however, that economic development, and particularly urbanization, has also been a causal factor.,The urbanization process results in profound socio-economic and landscape changes that reduce malaria transmission, but the magnitude and extent of these effects on global endemicity reductions are poorly understood.,Global data at subnational spatial resolution on changes in malaria transmission intensity and urbanization trends over the past century were combined to examine the relationships seen over a range of spatial and temporal scales.,A consistent pattern of increased urbanization coincident with decreasing malaria transmission and elimination over the past century was found.,Whilst it remains challenging to untangle whether this increased urbanization resulted in decreased transmission, or that malaria reductions promoted development, the results point to a close relationship between the two, irrespective of national wealth.,The continuing rapid urbanization in malaria-endemic regions suggests that such malaria declines are likely to continue, particularly catalyzed by increasing levels of direct malaria control.

Systematic non-compliance to chemotherapeutic treatment among a portion of the eligible population is thought to be a major obstacle to the elimination of helminth infections by mass drug administration (MDA).,MDA for helminths is repeated at defined intervals such as yearly or every 2 years, as a consequence of the inability of the human host to develop fully protective immunity to reinfection.,As such, how an individual complies to these repeated rounds of MDA can have a significant impact on parasite transmission.,The importance of this factor is poorly understood at present.,Few epidemiological studies have examined longitudinal trends in compliance in the many communities in areas of endemic helminth infection that are undergoing MDA.,Reducing systematic non-compliance will obviously increase the number of individuals treated, but it may also alter the dynamics of parasite transmission.,Here we develop an individual-based stochastic model of helminth transmission and MDA treatment to investigate how different patterns of compliance influence the impact of MDA for two groups of helminths, the soil transmitted nematode infections and the schistosome parasites.,We study the effect of several alternative treatment and compliance patterns on the dynamics of transmission.,We find that the impact of different compliance patterns, ranging from random treatment at each round of chemotherapy to systematic non-compliance by a proportion of the population, is very dependent on both transmission intensity in a defined setting and the type of infection that the treatment is targeted at.,Systematic non-compliance has a greater impact on the potential for elimination of Schistosoma mansoni transmission by intensive MDA, than it does on Ascaris lumbricoides.,We discuss the implications of our findings for the prioritisation of resources in MDA programmes and for monitoring and evaluation programme design.,The key message generated by the analyses is that great care must be taken to record individual longitudinal patterns of compliance at each round of MDA as opposed to just recording overall coverage.,The online version of this article (doi:10.1186/s13071-017-2206-5) contains supplementary material, which is available to authorized users.

The predictions of two mathematical models of the transmission dynamics of Ascaris lumbricoides and hookworm infection and the impact of mass drug administration (MDA) are compared, using data from India.,One model has an age structured partial differential equation (PDE) deterministic framework for the distribution of parasite numbers per host and sexual mating.,The second model is an individual-based stochastic model.,Baseline data acquired prior to treatment are used to estimate key transmission parameters, and forward projections are made, given the known MDA population coverage.,Predictions are compared with observed post-treatment epidemiological patterns.,The two models could equally well predict the short-term impact of deworming on A. lumbricoides and hookworm infection levels, despite being fitted to different subsets and/or summary statistics of the data.,As such, the outcomes give confidence in their use as aids to policy formulation for the use of PCT to control A. lumbricoides and hookworm infection.,The models further largely agree in a qualitative sense on the added benefit of semi-annual vs. annual deworming and targeting of the entire population vs. only children, as well as the potential for interruption of transmission.,Further, this study also illustrates that long-term predictions are sensitive to modelling assumptions about which age groups contribute most to transmission, which depends on human demography and age-patterns in exposure and contribution to the environmental reservoir of infection, the latter being notoriously difficult to empirically quantify.

The World Health Organization recommends that persons of all ages suspected of malaria should receive a parasitological confirmation of malaria by use of malaria rapid diagnostic test (RDT) at community level, and that rectal artesunate should be used as a pre-referral treatment for severe malaria to rapidly reduce parasitaemia.,This paper reports on findings from a pilot study that assessed the feasibility, acceptability and effects of integrating RDTs and pre-referral rectal artesunate into the integrated Community Case Management programme in Malawi.,This study used mixed methods to collect information for this survey.,Pre- and post-intervention, cross-sectional, household surveys were carried out.,A review of integrated community case management reports, including supervision checklists was conducted.,Quantitative data were collected in tablets running on open data kit software, and then data were transferred to STATA version 12 for analysis.,For key indicators, proportions were calculated at 95 % confidence intervals.,Qualitative data were recorded onto digital recorders, translated into English and transcribed for analysis.,Out of 86 observed RDT performances, a total of 83 (97 %) were performed correctly with a proper disposal of sharps and biohazard wastes.,Only two (2 %) febrile children who had an RDT negative result were treated with artemether-lumefantrine, contrary to malaria treatment guidelines.,Utilization of community health workers (CHWs) as a first source of care increased from (33.9 %) (95 % CI; 25.5-42.3) at baseline to (89.7 %) (95 % CI; 83.5-95.5) at end line in the intervention villages.,There was a corresponding decrease in the proportion of caregivers that first sought care from informal sources from 12.9 % (95 % CI; 6.9-18.9) to 1.9 % (95 % CI; 0.9-4.4) in the intervention villages.,Acceptability of the use of RDTs and pre-referral rectal artesunate at the community level was relatively high.,Integration of RDTs and pre-referral rectal at artesunate community level is both feasible and acceptable.,The strategy has the potential to increase and improve utilization of child health services at community level.,However, this depends on the CHWs’ skills and their availability in remote areas.

Malaria is commonly considered a disease of the poor, but there is very little evidence of a possible two-way causality in the association between malaria and poverty.,Until now, limitations to examine that dual relationship were the availability of representative data on confirmed malaria cases, the use of a good proxy for poverty, and accounting for endogeneity in regression models.,A simultaneous equation model was estimated with nationally representative data for Tanzania that included malaria parasite testing with RDTs for young children (six-59 months), and accounted for environmental variables assembled with the aid of GIS.,A wealth index based on assets, access to utilities/infrastructure, and housing characteristics was used as a proxy for socioeconomic status.,Model estimation was done with instrumental variables regression.,Results show that households with a child who tested positive for malaria at the time of the survey had a wealth index that was, on average, 1.9 units lower (p-value < 0.001), and that an increase in the wealth index did not reveal significant effects on malaria.,If malaria is indeed a cause of poverty, as the findings of this study suggest, then malaria control activities, and particularly the current efforts to eliminate/eradicate malaria, are much more than just a public health policy, but also a poverty alleviation strategy.,However, if poverty has no causal effect on malaria, then poverty alleviation policies should not be advertised as having the potential additional effect of reducing the prevalence of malaria.

Infection by helminth parasites is associated with amelioration of allergic reactivity, but mechanistic insights into this association are lacking.,Products secreted by the mouse parasite Heligmosomoides polygyrus suppress type 2 (allergic) immune responses through interference in the interleukin-33 (IL-33) pathway.,Here, we identified H. polygyrus Alarmin Release Inhibitor (HpARI), an IL-33-suppressive 26-kDa protein, containing three predicted complement control protein (CCP) modules.,In vivo, recombinant HpARI abrogated IL-33, group 2 innate lymphoid cell (ILC2) and eosinophilic responses to Alternaria allergen administration, and diminished eosinophilic responses to Nippostrongylus brasiliensis, increasing parasite burden.,HpARI bound directly to both mouse and human IL-33 (in the cytokine’s activated state) and also to nuclear DNA via its N-terminal CCP module pair (CCP1/2), tethering active IL-33 within necrotic cells, preventing its release, and forestalling initiation of type 2 allergic responses.,Thus, HpARI employs a novel molecular strategy to suppress type 2 immunity in both infection and allergy.,•HpARI is a suppressor of IL-33 release and consequent allergic sensitization•HpARI binds active IL-33 and nuclear DNA, tethering IL-33 within necrotic cells•HpARI is active against both human and murine IL-33,HpARI is a suppressor of IL-33 release and consequent allergic sensitization,HpARI binds active IL-33 and nuclear DNA, tethering IL-33 within necrotic cells,HpARI is active against both human and murine IL-33,Osbourn et al identified HpARI, a protein secreted by a helminth parasite that is capable of suppressing allergic responses.,HpARI binds to IL-33 (a critical inducer of allergy) and nuclear DNA, preventing the release of IL-33 from necrotic epithelial cells.

Eosinophil responses typify both allergic and parasitic helminth disease.,In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses.,To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae.,Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo.,Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses.,Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection.,In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE.,Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone.,However lack of eosinophils or MBP-1 actually increased goblet cell mucus production.,We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1.,These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity.

An increasing number of countries in sub-Saharan Africa are moving towards malaria-elimination, mostly thanks to successful vector control campaigns.,However, elimination has proven challenging, resulting in the persistence of malaria transmission.,It is now accepted that in order to eliminate malaria, new complementary vector control approaches must be developed.,This study describes the development of a sugar-baited resting place containing a toxic dose of ivermectin for the control of Anopheles arabiensis.,Dose response experiments were performed in insectary conditions to determine the LD90 of ivermectin against An. arabiensis.,Over 95% of An. arabiensis were knocked down 48 h post-sugar feeding on 10% sucrose solutions containing 0.01% ivermectin.,When investigating different juices as attractants, it was observed that An. arabiensis preferred orange, watermelon and commercial guava juice over pawpaw, tomato, mango or banana, but were most likely to feed on simple 10% sugar solution.,Using recycled materials, different bait prototypes were tested to determine the best design to maximize sugar feeding.,Baits that offered a resting place for the mosquito rather than just a surface to sugar feed were more likely to attract An. arabiensis to sugar feed.,The optimized prototype was then placed in different locations within a screen-house, colour-coded with different food dyes, containing competing vegetation (Ricinus communis) and experimental huts where humans slept under bed nets.,Around half of all the released An. arabiensis sugar fed on the sugar baits, and approximately 50% of all sugar fed mosquitoes chose the baits close to outdoor vegetation before entering the huts.,Ivermectin is an effective insecticide for use in sugar baits.,The design of the sugar bait can influence feeding rates and, therefore, efficacy.,Sugar baits that offer a resting surface are more efficient and sugar feeding on the baits is maximized when these are placed close to peri-domestic vegetation.,Attractive toxic sugar baited resting places may provide an additional vector control method to complement with existing strategies.

Manipulation of the mosquito gut microbiota can lay the foundations for novel methods for disease transmission control.,Mosquito blood feeding triggers a significant, transient increase of the gut microbiota, but little is known about the mechanisms by which the mosquito controls this bacterial growth whilst limiting inflammation of the gut epithelium.,Here, we investigate the gut epithelial response to the changing microbiota load upon blood feeding in the malaria vector Anopheles coluzzii.,We show that the synthesis and integrity of the peritrophic matrix, which physically separates the gut epithelium from its luminal contents, is microbiota dependent.,We reveal that the peritrophic matrix limits the growth and persistence of Enterobacteriaceae within the gut, whilst preventing seeding of a systemic infection.,Our results demonstrate that the peritrophic matrix is a key regulator of mosquito gut homeostasis and establish functional analogies between this and the mucus layers of the mammalian gastrointestinal tract.

Plasmodium vivax is the most prevalent human malaria parasite outside of Africa.,Yet, studies aimed to identify genes with signatures consistent with natural selection are rare.,Here, we present a comparative analysis of the pattern of genetic variation of five sequenced isolates of P. vivax and its divergence with two closely related species, Plasmodium cynomolgi and Plasmodium knowlesi, using a set of orthologous genes.,In contrast to Plasmodium falciparum, the parasite that causes the most lethal form of human malaria, we did not find significant constraints on the evolution of synonymous sites genome wide in P. vivax.,The comparative analysis of polymorphism and divergence across loci allowed us to identify 87 genes with patterns consistent with positive selection, including genes involved in the “exportome” of P. vivax, which are potentially involved in evasion of the host immune system.,Nevertheless, we have found a pattern of polymorphism genome wide that is consistent with a significant amount of constraint on the replacement changes and prevalent negative selection.,Our analyses also show that silent polymorphism tends to be larger toward the ends of the chromosomes, where many genes involved in antigenicity are located, suggesting that natural selection acts not only by shaping the patterns of variation within the genes but it also affects genome organization.

Plasmodium vivax is one of the major species of malaria infecting humans.,Although emphasis on P. falciparum is appropriate, the burden of vivax malaria should be given due attention.,This study aimed to synthesize the evidence on severe malaria in P. vivax infection compared with that in P. falciparum infection.,We searched relevant studies in electronic databases.,The main outcomes required for inclusion in the review were mortality, severe malaria (SM) and severe anaemia (SA).,The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale.,Overall, 26 studies were included.,The main meta-analysis was restricted to the high quality studies.,Eight studies (n = 27490) compared the incidence of SM between P. vivax infection and P. falciparum mono-infection; a comparable incidence was found in infants (OR: 0.45, 95% CI:0.04-5.68, I 2:98%), under 5 year age group (OR: 2.06, 95% CI: 0.83-5.1, I 2:83%), the 5-15 year-age group (OR: 0.6, 95% CI: 0.31-1.16, I 2:81%) and adults (OR: 0.83, 95% CI: 0.67-1.03, I 2:25%).,Six studies reported the incidences of SA in P. vivax infection and P. falciparum mono-infection; a comparable incidence of SA was found among infants (OR: 3.47, 95%:0.64-18.94, I 2: 92%), the 5-15 year-age group (OR:0.71, 95% CI: 0.06-8.57, I 2:82%).,This was significantly lower in adults (OR:0.75, 95% CI: 0.62-0.92, I 2:0%).,Five studies (n = 71079) compared the mortality rate between vivax malaria and falciparum malaria.,A lower rate of mortality was found in infants with vivax malaria (OR:0.61, 95% CI:0.5-0.76, I 2:0%), while this was comparable in the 5-15 year- age group (OR: 0.43, 95% CI:0.06-2.91, I 2:84%) and the children of unspecified-age group (OR: 0.77, 95% CI:0.59-1.01, I 2:0%).,Overall, the present analysis identified that the incidence of SM in patients infected with P. vivax was considerable, indicating that P. vivax is a major cause of SM.,Awareness of the clinical manifestations of vivax malaria should prompt early detection.,Subsequent treatment and monitoring of complications can be life-saving.

Interventions that interrupt Plasmodium vivax transmission or eliminate dormant P. vivax liver-stage parasites will be essential for malaria elimination.,Development of these interventions has been hindered by the lack of P. vivax in vitro culture and could be accelerated by a safe and reproducible clinical model in malaria-naive individuals.,Healthy, malaria-naive adults were enrolled in 2 studies to assess the safety, infectivity, and transmissibility of a new P. vivax isolate.,Participants (Study 1, n = 2; Study 2, n = 24) were inoculated with P. vivax-infected red blood cells to initiate infection, and were treated with artemether-lumefantrine (Study 1) or chloroquine (Study 2).,Primary endpoints were safety and infectivity of the new isolate.,In Study 2, transmission to mosquitoes was also evaluated using mosquito feeding assays, and sporozoite viability was assessed using in vitro cultured hepatocytes.,Parasitemia and gametocytemia developed in all participants and was cleared by antimalarial treatment.,Adverse events were mostly mild or moderate and none were serious.,Sixty-nine percent of participants (11/16) were infectious to Anopheles mosquitoes at peak gametocytemia.,Mosquito infection rates reached 97% following membrane feeding with gametocyte-enriched blood, and sporozoites developed into liver-stage schizonts in culture.,We have demonstrated the safe, reproducible, and efficient transmission of P. vivax gametocytes from humans to mosquitoes, and have established an experimental model that will accelerate the development of interventions targeting multiple stages of the P. vivax life cycle.,ACTRN12614000930684 and ACTRN12616000174482.,(Australian) National Health and Medical Research Council Program Grant 1132975 (Study 1).,Bill and Melinda Gates Foundation (OPP1111147) (Study 2).

Understanding the importance of gametocyte density on human-to-mosquito transmission is of immediate relevance to malaria control.,Previous work (Churcher et al., 2013) indicated a complex relationship between gametocyte density and mosquito infection.,Here we use data from 148 feeding experiments on naturally infected gametocyte carriers to show that the relationship is much simpler and depends on both female and male parasite density.,The proportion of mosquitoes infected is primarily determined by the density of female gametocytes though transmission from low gametocyte densities may be impeded by a lack of male parasites.,Improved precision of gametocyte quantification simplifies the shape of the relationship with infection increasing rapidly before plateauing at higher densities.,The mean number of oocysts per mosquito rises quickly with gametocyte density but continues to increase across densities examined.,The work highlights the importance of measuring both female and male gametocyte density when estimating the human reservoir of infection.

A major challenge for malaria is the lack of tools for accurate and timely diagnosis in the field which are critical for case management and surveillance.,Microscopy along with rapid diagnostic tests are the current mainstay for malaria diagnosis in most endemic regions.,However, these methods present several limitations.,This study assessed the accuracy of Gazelle, a novel rapid malaria diagnostic device, from samples collected from the Peruvian Amazon between 2019 and 2020.,Diagnostic accuracy was compared against microscopy and two rapid diagnostic tests (SD Bioline and BinaxNOW) using 18ssr nested-PCR as reference test.,In addition, a real-time PCR assay (PET-PCR) was used for parasite quantification.,Out of 217 febrile patients enrolled and tested, 180 specimens (85 P. vivax and 95 negatives) were included in the final analysis.,Using nested-PCR as the gold standard, the sensitivity and specificity of Gazelle was 88.2% and 97.9%, respectively.,Using a cutoff of 200 parasites/μl, Gazelle’s sensitivity for samples with more than 200 p/uL was 98.67% (95%CI: 92.79% to 99.97%) whereas the sensitivity for samples lower than 200 p/uL (n = 10) was 12.5% (95%CI: 0.32% to 52.65%).,Gazelle’s sensitivity and specificity were statistically similar to microscopy (sensitivity = 91.8, specificity = 100%, p = 0.983) and higher than both SD Bioline (sensitivity = 82.4, specificity = 100%, p = 0.016) and BinaxNOW (sensitivity = 71.8%, specificity = 97.9%, p = 0.002).,The diagnostic accuracy of Gazelle for malaria detection in P. vivax infections was comparable to light microscopy and superior to both RDTs even in the presence of low parasitemia infections.,The performance of Gazelle makes it a valuable tool for malaria diagnosis and active case detection that can be utilized in different malaria-endemic regions.

This study describes the laboratory evaluation of a novel diagnostic platform for malaria.,The Magneto Optical Test (MOT) is based on the bio-physical detection of haemozoin in clinical samples.,Having an assay time of around one minute, it offers the potential of high throughput screening.,Blood samples of confirmed malaria patients from different regions of Africa, patients with other diseases and healthy non-endemic controls were used in the present study.,The samples were analysed with two reference tests, i.e. an histidine rich protein-2 based rapid diagnostic test (RDT) and a conventional Pan-Plasmodium PCR, and the MOT as index test.,Data were entered in 2 × 2 tables and analysed for sensitivity and specificity.,The agreement between microscopy, RDT and PCR and the MOT assay was determined by calculating Kappa values with a 95% confidence interval.,The observed sensitivity/specificity of the MOT test in comparison with clinical description, RDT or PCR ranged from 77.2 - 78.8% (sensitivity) and from 72.5 - 74.6% (specificity).,In general, the agreement between MOT and the other assays is around 0.5 indicating a moderate agreement between the reference and the index test.,However, when RDT and PCR are compared to each other, an almost perfect agreement can be observed (k = 0.97) with a sensitivity and specificity of >95%.,Although MOT sensitivity and specificity are currently not yet at a competing level compared to other diagnostic test, such as PCR and RDTs, it has a potential to rapidly screen patients for malaria in endemic as well as non-endemic countries.

Malaria transmission is highly heterogeneous, generating malaria hotspots that can fuel malaria transmission across a wider area.,Targeting hotspots may represent an efficacious strategy for reducing malaria transmission.,We determined the impact of interventions targeted to serologically defined malaria hotspots on malaria transmission both inside hotspots and in surrounding communities.,Twenty-seven serologically defined malaria hotspots were detected in a survey conducted from 24 June to 31 July 2011 that included 17,503 individuals from 3,213 compounds in a 100-km2 area in Rachuonyo South District, Kenya.,In a cluster-randomized trial from 22 March to 15 April 2012, we randomly allocated five clusters to hotspot-targeted interventions with larviciding, distribution of long-lasting insecticide-treated nets, indoor residual spraying, and focal mass drug administration (2,082 individuals in 432 compounds); five control clusters received malaria control following Kenyan national policy (2,468 individuals in 512 compounds).,Our primary outcome measure was parasite prevalence in evaluation zones up to 500 m outside hotspots, determined by nested PCR (nPCR) at baseline and 8 wk (16 June-6 July 2012) and 16 wk (21 August-10 September 2012) post-intervention by technicians blinded to the intervention arm.,Secondary outcome measures were parasite prevalence inside hotpots, parasite prevalence in the evaluation zone as a function of distance from the hotspot boundary, Anopheles mosquito density, mosquito breeding site productivity, malaria incidence by passive case detection, and the safety and acceptability of the interventions.,Intervention coverage exceeded 87% for all interventions.,Hotspot-targeted interventions did not result in a change in nPCR parasite prevalence outside hotspot boundaries (p ≥ 0.187).,We observed an average reduction in nPCR parasite prevalence of 10.2% (95% CI −1.3 to 21.7%) inside hotspots 8 wk post-intervention that was statistically significant after adjustment for covariates (p = 0.024), but not 16 wk post-intervention (p = 0.265).,We observed no statistically significant trend in the effect of the intervention on nPCR parasite prevalence in the evaluation zone in relation to distance from the hotspot boundary 8 wk (p = 0.27) or 16 wk post-intervention (p = 0.75).,Thirty-six patients with clinical malaria confirmed by rapid diagnostic test could be located to intervention or control clusters, with no apparent difference between the study arms.,In intervention clusters we caught an average of 1.14 female anophelines inside hotspots and 0.47 in evaluation zones; in control clusters we caught an average of 0.90 female anophelines inside hotspots and 0.50 in evaluation zones, with no apparent difference between study arms.,Our trial was not powered to detect subtle effects of hotspot-targeted interventions nor designed to detect effects of interventions over multiple transmission seasons.,Despite high coverage, the impact of interventions targeting malaria vectors and human infections on nPCR parasite prevalence was modest, transient, and restricted to the targeted hotspot areas.,Our findings suggest that transmission may not primarily occur from hotspots to the surrounding areas and that areas with highly heterogeneous but widespread malaria transmission may currently benefit most from an untargeted community-wide approach.,Hotspot-targeted approaches may have more validity in settings where human settlement is more nuclear.,ClinicalTrials.gov NCT01575613,In a cluster-randomized controlled trial, Teun Bousema and colleagues investigate whether interventions targeted to malaria hotspots in the western Kenyan highlands can reduce transmission in surrounding areas.,In 2015, there were about 200 million cases of malaria (a mosquito-borne parasitic disease) worldwide and about 438,000 malaria-related deaths.,Most of these deaths were caused by Plasmodium falciparum, which is transmitted to people by night-flying Anopheles mosquitoes.,When infected mosquitoes bite people, they inject “sporozoites,” a parasitic form that replicates in the liver.,After a few days, the liver releases “merozoites,” which invade red blood cells, where they replicate before bursting out and infecting more red blood cells.,This increase in parasitic burden causes recurring flu-like symptoms and can cause organ damage and death if not treated promptly with antimalarial drugs.,Infected red blood cells also release “gametocytes,” which infect mosquitoes when they take a blood meal.,In the mosquito, gametocytes multiply and develop into sporozoites, which completes the parasite’s life cycle.,Malaria can be prevented by controlling Anopheles mosquitoes and by avoiding mosquito bites.,Methods for controlling mosquitoes include treating stagnant water with “larvicides” to kill immature mosquitoes and spraying houses with insecticides (indoor residual spraying); sleeping under insecticide-treated bednets is an effective way to avoid mosquito bites.,Treatment with antimalarial drugs also decreases malaria transmission.,Improved malaria prevention has reduced malaria-related deaths over recent years, and experts are now trying to devise strategies to eradicate malaria.,Targeting malaria transmission hotspots-regions where the intensity of transmission is higher than in surrounding areas-is one potential strategy for reducing malaria transmission.,Mosquito densities are highest in hotspots, and people living in hotspots may transmit malaria parasites to a large number of mosquitoes that can then spread malaria transmission to wider areas.,Targeting malaria hotspots might, therefore, benefit communities in both the targeted region and the surrounding area.,Here, the researchers look for malaria hotspots in Rachuonyo South District in the western Kenyan highlands, an area where malaria transmission intensity is generally low, and undertake a cluster-randomized controlled trial to determine the impact of hotspot-targeted malaria control interventions on malaria transmission inside hotspots and in surrounding communities.,A cluster-randomized trial compares outcomes in groups (clusters) of people (here, people living in different malaria hotspots) randomly assigned to receive different interventions.,Using survey results and spatial scanning techniques, the researchers detected 27 serologically defined malaria hotpots (clusters of people with antibodies to the malaria parasite) in Rachuonyo South District.,Of these, ten hotspots were at least 1.5 kilometers from the nearest neighboring hotspot (allowing space for evaluation zones and a buffer between hotspots).,During the following peak malaria transmission period, they randomly allocated five of these hotspots to targeted interventions (larvicide treatment of stagnant water, community distribution of insecticide-treated bednets, indoor residual spraying, and mass drug administration) and five hotspots to the control intervention (the Kenyan national policy of annual indoor residual spraying, routine case management at clinics, and bednet distribution at antenatal clinics).,Intervention coverage exceeded 87% for all the components of the targeted intervention.,However, the intervention did not change the prevalence of parasites (the proportion of the population carrying parasites) at 8 or 16 weeks post-intervention in the evaluation zones-the areas 1-500 meters from the border of the hotspots (the study’s primary outcome).,There was a statistically significant reduction in parasite prevalence inside intervention hotspots at 8 but not 16 weeks post-intervention (a statistically significant change is one unlikely to have happened by chance).,Finally, similar numbers of individuals from the intervention and control clusters attended local health facilities and were found to have confirmed clinical malaria, and there was no significant difference between intervention and control clusters in the number of mosquitoes caught within hotspots or evaluation zones.,These findings show that, despite high coverage, the impact of interventions targeting malaria hotspots in Rachuonyo South District on parasite prevalence was modest, transient, and restricted to the targeted hotspot.,It may be that the number of clusters included in this study was too small to detect any subtle effects of hotspot-targeted interventions.,Moreover, the effect of the targeted interventions may have been masked by other ongoing interventions in the region.,However, these findings suggest that malaria transmission in Rachuonyo South District may not occur primarily from hotspots to the surrounding areas.,Thus, areas where malaria transmission is widespread but includes hotspots might benefit most from an untargeted community-wide approach to malaria prevention.,This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001993.,Information is available from the World Health Organization on malaria (in several languages); its Global Technical Strategy for Malaria 2016-2030 provides a framework to guide countries towards malaria elimination; the World Malaria Report 2015 describes the current global malaria situation and includes information on malaria in individual African countries and recommended policies and strategies for malaria control,The US Centers for Disease Control and Prevention provides information on malaria (in English and Spanish), including information about malaria prevention and personal stories about malaria,The UK National Health Service Choices website also provides information about malaria, including a personal story,Information is available from the Roll Back Malaria Partnership on the global control of malaria (in English and French),MedlinePlus provides links to additional information on malaria (in English and Spanish),More information about this trial is available

Malaria rapid diagnostic tests (RDTs) play a key role in malaria management and control.,The PfHRP-2 based RDT is the most widely used RDT for malaria diagnosis in Ghana.,Deletion of pfhrp2 in Plasmodium falciparum parasites affect the diagnostic accuracy of PfHRP-2 based RDT kits.,Identifying the prevalence and distribution of P. falciparum parasites with deleted pfhrp2 is important for malaria control.,The purpose of this study was to identify and confirm the prevalence of pfhrp2 deletant P. falciparum parasites circulating within different regions of Ghana.,DNA was extracted from the membrane of spent CareStart™ PfHRP-2 RDT kits and dried filter paper blood blots using Chelex-100.,Exon 2 of pfhrp2 and pfhrp3 genes were amplified by polymerase chain reaction (PCR), resolved by agarose gel electrophoresis and visualized under UV light.,Microscopic analysis of blood smears from samples that were PfHRP-2 RDT positive revealed a parasite prevalence of 54/114 (47.4 %) and 2/26 (7.7 %) in Accra and Cape Coast, respectively.,PCR analysis increased parasite prevalence in the RDT positive samples to 94/114 (82.5 %) and 6/26 (23.1 %) in Accra and Cape Coast respectively.,The exon 2 of the pfhrp2 gene was deleted in 18/54 (33.3 %) of the microscopy confirmed and 36.2 % (34/94) of the PCR confirmed RDT positive samples collected in Accra.,No RDT sample, confirmed to contain parasites by either PCR or microscopy was negative by pfhrp2 exon 2 PCR in Cape Coast.,A survey of an additional 558 DBS revealed that 22.4 % (46/205) and 40 % (44/110) of PCR positive samples in Accra and Cape Coast, respectively, lacked the exon 2 region of pfhrp2 and possibly the entire pfhrp2 gene.,A high number of P. falciparum parasites, which lack pfhrp2 exon 2 gene have been identified in two communities in Ghana.,Continuous nationwide monitoring of the prevalence of pfhrp2 deletant parasites would be essential to malaria control.,The use of RDT kits that are effective at malaria diagnosis despite deletion of pfhrp2, such as the PfHRP-2/PfLDH combo RDT kit could enhance the diagnosis of clinical malaria in Ghana.