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IntroductionAlternative drugs and diagnostics are needed for the treatment and control of schistosomiasis. The exclusive use of praziquantel (PZQ) in mass drug administration programmes may result in the emergence of drug resistance. PZQ has little activity againstSchistosomalarvae, thus reinfection remains a problem in high-risk communities. Furthermore, the insufficient sensitivity of conventional microscopy hinders therapeutic response assessment. Evaluation of artesunate-mefloquine (AM) as a Novel Alternative Treatment for Schistosomiasis in African Children (SchistoSAM) aims to evaluate the safety and efficacy of the antimalarial combination artesunate-mefloquine, re-purposed for the treatment of schistosomiasis, and to assess the performance of highly sensitive novel antigen-based and DNA-based assays as tools for monitoring treatment response.Methods and analysisThe SchistoSAM study is an open-label, two-arm, individually randomised controlled non-inferiority trial, with a follow-up of 48 weeks. Primary school-aged children from the Richard Toll district in northern Senegal, an area endemic forSchistosoma mansoniandSchistosoma haematobium, are allocated to the AM intervention arm (3-day courses at 6-week intervals) or the PZQ control arm (single dose of 40 mg/kg). The trial’s primary endpoints are the efficacy (cure rate (CR), assessed by microscopy) and safety (frequency and pattern of drug-related adverse events) of one AM course versus PZQ at 4 weeks after treatment. Secondary endpoints include (1) cumulative CR, egg reduction rate and safety after each additional course of AM, and at weeks 24 and 48, (2) prevalence and severity of schistosomiasis-related morbidity and (3) malaria prevalence, incidence and morbidity, both after 24 and 48 weeks. CRs and intensity reduction rates are also assessed by antigen-based and DNA-based diagnostic assays, for which performance for treatment monitoring is evaluated.Ethics and disseminationEthics approval was obtained both in Belgium and Senegal. Oral assent from the children and signed informed consent from their legal representatives was obtained, prior to enrolment. The results will be disseminated in peer-reviewed journals and at international conferences.Trial registration numberNCT03893097; pre-results.

The dampened course of COVID-19 in Africa might reveal innovative solutions

In central Senegal, malaria incidence declined in response to scaling-up of control measures from 2000 to 2010 and has since remained stable, making elimination unlikely in the short term. Additional control measures are needed to reduce transmission. We simulated chemoprophylaxis interventions targeting malaria hotspots using a metapopulation mathematical model, based on a differential-equation framework and incorporating human mobility. The model was fitted to weekly malaria incidence from 45 villages. Three approaches for selecting intervention targets were compared: (a) villages with malaria cases during the low transmission season of the previous year, (b) villages with highest incidence during the high transmission season of the previous year, (c) villages with highest connectivity with adjacent populations. Our results showed that intervention strategies targeting hotspots would be effective in reducing malaria incidence in both targeted and untargeted areas. Regardless of the intervention strategy used, pre-elimination (1&ndash, 5 cases per 1000 per year) would not be reached without simultaneously increasing vector control by more than 10%. A cornerstone of malaria control and elimination is the effective targeting of strategic locations. Mathematical tools help to identify those locations and estimate the impact in silico.

BACKGROUND NlmCategory: BACKGROUND content: Population-wide interventions using malaria testing and treatment might decrease the reservoir of Plasmodium falciparum infection and accelerate towards elimination. Questions remain about their effectiveness and evidence from different transmission settings is needed. - Label: METHODS NlmCategory: METHODS content: "A pilot quasi-experimental study to evaluate a package of population-wide test and treat interventions was conducted in six health facility catchment areas (HFCA) in the districts of Kanel, Lingu\xC3\xA8re, and Ran\xC3\xA9rou (Senegal). Seven adjacent HFCAs were selected as comparison. Villages within the intervention HFCAs were stratified according to the 2013 incidences of passively detected malaria cases, and those with an incidence\xE2\x80\x89\xE2\x89\xA5\xE2\x80\x8915 cases/1000/year were targeted for a mass test and treat (MTAT) in September 2014. All households were visited, all consenting individuals were tested with a rapid diagnostic test (RDT), and, if positive, treated with dihydroartemisinin-piperaquine. This was followed by weekly screening, testing and treatment of fever cases (PECADOM++) until the end of the transmission season in January 2015. Villages with lower incidence received only PECADOM++ or case investigation. To evaluate the impact of the interventions over that transmission season, the incidence of passively detected, RDT-confirmed malaria cases was compared between the intervention and comparison groups with a difference-in-difference analysis using negative binomial regression with random effects on HFCA." - Label: RESULTS NlmCategory: RESULTS content: "During MTAT, 89% (2225/2503) of households were visited and 86% (18,992/22,170) of individuals were tested, for a combined 77% effective coverage. Among those tested, 291 (1.5%) were RDT positive (range 0-10.8 by village), of whom 82% were\xE2\x80\x89

Background Effective targeting of malaria control in low transmission areas requires identification of transmission foci or hotspots. We investigated the use of functional data analysis to identify and describe spatio-temporal pattern of malaria incidence in an area with seasonal transmission in west-central Senegal. Method Malaria surveillance was maintained over 5 years from 2008 to 2012 at health facilities serving a population of 500,000 in 575 villages in two health districts in Senegal. Smooth functions were fitted from the time series of malaria incidence for each village, using cubic B-spline basis functions. The resulting smooth functions for each village were classified using hierarchical clustering (Ward’s method), using several different dissimilarity measures. The optimal number of clusters was then determined based on four cluster validity indices, to determine the main types of distinct temporal pattern of malaria incidence. Epidemiological indicators characterizing the resulting malaria incidence pattern in terms of the timing of seasonal outbreaks, were calculated based on the slope (velocity) and rate of change of the slope (acceleration) of the incidence over time. Results Three distinct patterns of malaria incidence were identified. A pattern characterized by high incidence, in 12/575 (2%) villages, with average incidence of 114 cases/1000 person-years over the 5 year study period; a pattern with intermediate incidence in 97 villages (17%), with average incidence of 13 cases/1000 person-years; and a pattern with low incidence in 466 (81%) villages, with average incidence 2.6 cases/1000 person-years. Epidemiological indicators characterizing the fluctuations in malaria incidence showed that seasonal outbreaks started later, and ended earlier, in the low incidence pattern. Conclusion Functional data analysis can be used to classify communities based on time series of malaria incidence, and to identify high incidence communities. Indicators can be derived from the fitted functions which characterize the timing of outbreaks. These tools may help to better target control measures.

Background In malaria endemic areas, identifying spatio-temporal hotspots is becoming an important element of innovative control strategies targeting transmission bottlenecks. The aim of this work was to describe the spatio-temporal variation of malaria hotspots in central Senegal and to identify the meteorological, environmental, and preventive factors that influence this variation. Methods This study analysed the weekly incidence of malaria cases recorded from 2008 to 2012 in 575 villages of central Senegal (total population approximately 500,000) as part of a trial of seasonal malaria chemoprevention (SMC). Data on weekly rainfall and annual vegetation types were obtained for each village through remote sensing. The time series of weekly malaria incidence for the entire study area was divided into periods of high and low transmission using change-point analysis. Malaria hotspots were detected during each transmission period with the SaTScan method. The effects of rainfall, vegetation type, and SMC intervention on the spatio-temporal variation of malaria hotspots were assessed using a General Additive Mixed Model. Results The malaria incidence for the entire area varied between 0 and 115.34 cases/100,000 person weeks during the study period. During high transmission periods, the cumulative malaria incidence rate varied between 7.53 and 38.1 cases/100,000 person-weeks, and the number of hotspot villages varied between 62 and 147. During low transmission periods, the cumulative malaria incidence rate varied between 0.83 and 2.73 cases/100,000 person-weeks, and the number of hotspot villages varied between 10 and 43. Villages with SMC were less likely to be hotspots (OR = 0.48, IC95%: 0.33–0.68). The association between rainfall and hotspot status was non-linear and depended on both vegetation type and amount of rainfall. The association between village location in the study area and hotspot status was also shown. Conclusion In our study, malaria hotspots varied over space and time according to a combination of meteorological, environmental, and preventive factors. By taking into consideration the environmental and meteorological characteristics common to all hotspots, monitoring of these factors could lead targeted public health interventions at the local level. Moreover, spatial hotspots and foci of malaria persisting during LTPs need to be further addressed. Trial registration The data used in this work were obtained from a clinical trial registered on July 10, 2008 at www.clinicaltrials.gov under NCT00712374.

The implementation of effective malaria control strategies in the central-western Senegal, such as Indoor Residual Spraying (IRS), long-lasting insecticide-treated nets (LLIN), Seasonal malaria chemoprophylaxis (SMC) and appropriate management of malaria cases, has led to the decline of malaria transmission in the region. However, residual malaria transmission still occurring in some localities, known as hotspots villages, making challenging the achievement of the malaria elimination goal. A pilot study was undertaken between 2013 and 2014 to test the feasibility of a community-based IRS approach for malaria elimination in four targeted health districts of the Central Western Senegal.The residual efficacy of the Actellic® 300CS formulation on the sprayed surface was monitored using WHO cone test.Overall, 615 walls were tested over the two successive years, respectively 240 and 375 in 2013 and 2014 IRS campaigns. The residual efficacy of the IRS with Actellic®300 CS was longer in the second year due to the improvement of community agents spraying skill the second year thanks to the refreshing training and a better supervision by professional agent of the National Hygiene Service. The analysis of the Incidence Rate Ratio under the Poisson model shows no significant difference of IRS effectiveness according to the building type.In conclusion, the quality of training of community agents and good supervision of IRS activities play a key role in the quality and the residual efficacy of IRS campaigns. A good planning and implementation of IRS campaign ensure a high quality and a good effectiveness of spraying with the Actellic®300 CS formulation. Keywords: Malaria, Elimination, IRS, Hotspots, Community agents, Senegal

Dans les districts sanitaires de Mbour, Fatick, Niakhar et Bambey, situes au centre-ouest du Senegal, l’utilisation de mesures de lutte efficaces a fait fortement baisser l’incidence du paludisme qui n’est actuellement sensible que dans des foyers residuels de transmission encore appeles hotspots. Cette etude fait le point sur la place des gites larvaires d’anophele dans la selection des hotspots dans cette partie du Senegal. Les prospections des gites larvaires ont ete faites dans 6 villages hotspots et 4 villages non hotspots. Un prelevement a ete effectue dans chaque point d’eau presentant des larves de moustiques par la methode de dipping et les specimens collectes ont ete identifies au niveau genre. Des parametres complementaires ont ete aussi releves: nom du village et du gite, type de collection, origine de l’eau, turbidite, presence de vegetation, la proximite des habitations, coordonnees geographiques, dimensions. Au total soixantedeux stations ont ete prospectees et surveillees entre 2013 et 2014. Les gites naturels temporaires ont ete predominants quel que soit le statut epidemiologique du village. Sur les 31 gites situes a moins de 500 metres des habitations dans les villages hotspots, 70 % etaient positifs en larves d’anopheles en milieu de saison des pluies alors que 43 % des 21 gites situes a des distances similaires dans les villages non hotspots etaient positifs pendant la meme periode (P=0,042

Highlights • Antibody dynamics and role in young the infants’ low susceptibility to febrile malaria were investigated. • No evidence for association of antibody titres with clinical protection was found. • Evidence for consistently low antibody titres in high and low transmission areas. • Other antibodies, other antibody-mediated mechanisms or other protecting factors may be operating., Background Young infants have reduced susceptibility to febrile malaria compared with older children, but the mechanism for this remains unclear. There are conflicting data on the role of passively acquired antibodies. Here, we examine antibody titres to merozoite surface antigens in the protection of children in their first two years of life in two settings with differing malaria transmission intensity and compare these titres to previously established protective thresholds. Methods Two cohorts of children aged four to six weeks were recruited in Banfora, Burkina and Keur Soce, Senegal and followed up for two years. Malaria infections were detected by light microscopic examination of blood smears collected at active and passive case detection visits. The titres of antibodies to the Plasmodium falciparum recombinant merozoite proteins (AMA1-3D7, MSP1-19, MSP2-Dd2, and MSP3-3D7) were measured by enzyme-linked immunosorbent assay at 1–6, 9, 12, 15 and 18 months of age and compared with the protective thresholds established in Kenyan children. Results Antibody titres were below the protective thresholds throughout the study period and we did not find any association with protection against febrile malaria. Antibodies to AMA1 and MSP1-19 appeared to be markers of exposure in the univariate analysis (and so associated with increasing risk) and adjusting for exposure reduced the strength and significance of this association. Conclusion The antibody levels we measured are unlikely to be responsible for the apparent protection against febrile malaria seen in young infants. Further work to identify protective antibody responses might include functional assays and a wider range of antigens.

SMC has been introduced widely in the Sahel since its recommendation by WHO in 2012. This study, which provided evidence of feasibility that supported the recommendation, included school-age and pre-school children. School-age children were not included in the 2012 recommendation but bear an increasing proportion of cases. In 2006, consultations with health-staff were held to choose delivery methods. The preferred approach, door-to-door with the first daily-dose supervised by a community-health-worker (CHW), was piloted and subsequently evaluated on a large-scale in under-5's in 2008 and then in under-10's 2009-2010. Coverage was higher among school-age children (96%(95%CI 94%,98%) received three treatments in 2010) than among under 5's (90%(86%,94%)). SMC was more equitable than LLINs (odds-ratio for increase in coverage for a one-level rise in socioeconomic-ranking (a 5-point scale), was 1.1 (0.95,1.2) in 2009, compared with OR 1.3 (1.2,1.5) for sleeping under an LLIN. Effective communication was important in achieving high levels of uptake. Continued training and supervision were needed to ensure CHWs adhered to treatment guidelines. SMC door-to-door can, if carefully supervised, achieve high equitable coverage and high-quality delivery. SMC programmes can be adapted to include school-age children, a neglected group that bears a substantial burden of malaria.

Background Scaling-up of effective anti-malarial control strategies in Central-West region of Senegal has resulted in the sharp decline in malaria prevalence in this area. However, despite these strategies, residual malaria transmission has been observed in some villages (hot spots). The objective of this study was to assess the impact of indoor residual spraying (IRS) with pirimiphos-methyl on malaria transmission in hot spot areas. Methods The malaria vector population dynamics were monitored in each of the six selected villages (4 of which used IRS, 2 were unsprayed control areas) using overnight human landing catches (HLC) and pyrethrum spray catches (PSC). The host source of blood meals from freshly fed females collected using PSC was identified using the direct ELISA method. Females caught through HLC were tested by ELISA for the detection of Plasmodium falciparum circumsporozoite protein and Anopheles gambiae complex was identified using PCR. Results Preliminary data shown that the densities of Anopheles populations were significantly lower in the sprayed areas (179/702) compared to the control. Overall, malaria transmission risk was 14 times lower in the intervention zone (0.94) compared to the control zone (12.7). In the control areas, three Anopheles species belonging to the Gambiae complex (Anopheles arabiensis, Anopheles coluzzii and Anopheles melas) maintained the transmission, while only An. coluzzii was infective in the sprayed areas. Conclusion The preliminary data from this pilot study showed that IRS with the CS formulation of pirimiphos-methyl is likely very effective in reducing malaria transmission risk. However, additional studies including further longitudinal entomological surveys as well as ecological and ethological and genetical characterization of vectors species and their populations are needed to better characterize the entomological impact of indoor residual spraying with pirimiphos-methyl in the residual transmission areas of Senegal.

Resume La regression de l’endemie palustre constatee dans certaines zones au centre du Senegal laisse entrevoir l’espoir d’une elimination de cette pathologie qui constitue un lourd fardeau en termes de morbidite et de mortalite. En effet dans les districts de Mbour, Fatick, Niakhar et Bambey, situes au centre-ouest du Senegal, le paludisme evolue en foyers de transmissions residuelles (hot spots) suite aux efforts de lutte realises ces dernieres annees. Le but de cet essai d’elimination est de mener une lutte intensifiee et ciblee sur les hot spots en utilisant des strategies a efficacite prouvee a savoir l’aspersion intradomiciliaire (AID) d’insecticide a effet remanent et la chimio prevention. L’AID est une intervention tres lourde dans sa mise en oeuvre et necessite une grande adhesion des populations. Apres sa mise en oeuvre en aout 2013 au niveau de 4 districts du centre-ouest du Senegal, une enquete d’acceptabilite de l’intervention a ete realisee sur un echantillon aleatoire de 370 menages. Les resultats de cette enquete ont revele une bonne acceptabilite de l’intervention avec 97,8 % des personnes interrogees qui jugent que l’AID est bien et meme excellente pour la communaute. Malgre les desagrements que peuvent engendrer cette activite, notamment la preparation des structures a traiter, 98 % des personnes interrogees estiment ne pas avoir ete perturbees dans leurs activites quotidiennes. Le comportement des applicateurs a ete juge exemplaire et professionnel par 98,6 % de l’echantillon de menages et la quasi-totalite (99,7 %) accepteraient que leurs structures soient traitees a nouveau l’annee suivante. Sur le plan pratique, la pulverisation avec l’Actellic ® 300 CS (pirimiphos-methyl, organophosphore) n’a pas occasionne de problemes majeurs aux populations beneficiaires. Au final, nous avons constate une grande satisfaction de la population des villages traites, en particulier en raison d’une forte reduction des nuisances causees par les insectes.

Seasonal Malaria Chemoprevention (SMC) is recommended for children under 5 in the Sahel and sub-Sahel. The burden in older children may justify extending the age range, as has been done effectively in Senegal. We examine costs of door-to-door SMC delivery to children up to 10 years by community health workers (CHWs). We analysed incremental financial and economic costs at district level and below from a health service perspective. We examined project accounts and prospectively collected data from 405 CHWs, 46 health posts, and 4 district headquarters by introducing questionnaires in advance and completing them after each monthly implementation round. Affordability was explored by comparing financial costs of SMC to relevant existing health expenditure levels. Costs were disaggregated by administration month and by health service level. We used linear regression models to identify factors associated with cost variation between health posts. The financial cost to administer SMC to 180 000 children over one malaria season, reaching ∼93% of children with all three intended courses of SMC was $234 549 (constant 2010 USD) or $0.50 per monthly course administered. Excluding research–participation incentives, the financial cost was $0.32 per resident (all ages) in the catchment area, which is 1.2% of Senegal’s general government expenditure on health per capita. Economic costs were 18.7% higher than financial costs at $278 922 or $0.59 per course administered and varied widely between health posts, from $0.38 to $2.74 per course administered. Substantial economies of scale across health posts were found, with the smallest health posts incurring highest average costs per monthly course administered. SMC for children up to 10 is likely to be affordable, particularly where it averts substantial curative care costs. Estimates of likely costs and cost-effectiveness of SMC in other contexts must account for variation in average costs across delivery months and health posts.

Introduction En epidemiologie, il est frequent d’etudier des variables fonctionnelles pour lesquelles les observations sont realisees de facon discrete (courbe de croissance, ECG, etc.). C’est le cas des series temporelles d’incidences. L’etude des dynamiques epidemiques doit prendre en compte cette nature fonctionnelle, en estimant et analysant les fonctions a l’origine des observations plutot qu’en analysant les donnees individuelles elle-meme. L’objectif de notre travail etait de rechercher des profils epidemiques en tenant compte de la nature fonctionnelle des series temporelles d’incidences pour optimiser les actions de lutte ciblees. Methodes L’analyse a porte sur le nombre de cas de paludisme hebdomadaire et la population annuelle de 620 villages du Senegal de janvier 2008 a decembre 2012. Les 620 fonctions continues d’incidences ont ete estimees en utilisant une base de Fourier, tenant compte de leur periodicite annuelle. Les profils epidemiques ont ete obtenus par classification hierarchique ascendante sur ces fonctions utilisant la distance euclidienne adaptee aux donnees fonctionnelles Eq. (1) et la methode de Ward. Les rapports d’incidences associes a chaque profil ont ete estimes a l’aide d’un modele additif generalise. Resultats La classification des courbes d’incidences a permis d’obtenir trois profils epidemiques de paludisme : un profil d’incidences basses (taux d’incidence : 4 cas/100 000 habitants semaine) avec des durees epidemiques restreinte (duree moyenne : 22 semaines) et pas de cas entre les epidemies annuelles, un profil d’incidences hautes (186 cas/100 000 habitants semaine) avec des durees epidemiques importantes (33 semaines) et toujours des cas persistants, et entre les deux, un profil intermediaire (25 cas/100 000 habitants semaine) avec une duree epidemique moyenne de 24 semaines. Malgre un aspect spatialement tres disperse, les villages du profil « bas » etaient majoritairement au nord de la zone d’etude, ceux du profil « haut » majoritairement au sud et ceux du profil « intermediaire » presents aussi bien au nord qu’au sud. Par rapport au profil intermediaire, le rapport standardise d’incidence du profil bas etait de 0,17 (IC95 % [0,15 ; 0,19], p Conclusion L’analyse realisee a permis de prendre en compte le caractere fonctionnel des courbes epidemiques indiquant ainsi trois dynamiques temporelles differentes du paludisme.

Background Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ), given each month during the transmission season, is recommended for children living in areas of the Sahel where malaria transmission is highly seasonal. The recommendation for SMC is currently limited to children under five years of age, but, in many areas of seasonal transmission, the burden in older children may justify extending this age limit. This study was done to determine the effectiveness of SMC in Senegalese children up to ten years of age. Methods and Findings SMC was introduced into three districts over three years in central Senegal using a stepped-wedge cluster-randomised design. A census of the population was undertaken and a surveillance system was established to record all deaths and to record all cases of malaria seen at health facilities. A pharmacovigilance system was put in place to detect adverse drug reactions. Fifty-four health posts were randomised. Nine started implementation of SMC in 2008, 18 in 2009, and a further 18 in 2010, with 9 remaining as controls. In the first year of implementation, SMC was delivered to children aged 3–59 months; the age range was then extended for the latter two years of the study to include children up to 10 years of age. Cluster sample surveys at the end of each transmission season were done to measure coverage of SMC and the prevalence of parasitaemia and anaemia, to monitor molecular markers of drug resistance, and to measure insecticide-treated net (ITN) use. Entomological monitoring and assessment of costs of delivery in each health post and of community attitudes to SMC were also undertaken. About 780,000 treatments were administered over three years. Coverage exceeded 80% each month. Mortality, the primary endpoint, was similar in SMC and control areas (4.6 and 4.5 per 1000 respectively in children under 5 years and 1.3 and 1.2 per 1000 in children 5-9 years of age; the overall mortality rate ratio [SMC: no SMC] was 0.90, 95% CI 0.68–1.2, p = 0.496). A reduction of 60% (95% CI 54%–64%, p < 0.001) in the incidence of malaria cases confirmed by a rapid diagnostic test (RDT) and a reduction of 69% (95% CI 65%–72%, p < 0.001) in the number of treatments for malaria (confirmed and unconfirmed) was observed in children. In areas where SMC was implemented, incidence of confirmed malaria in adults and in children too old to receive SMC was reduced by 26% (95% CI 18%–33%, p < 0.001) and the total number of treatments for malaria (confirmed and unconfirmed) in these older age groups was reduced by 29% (95% CI 21%–35%, p < 0.001). One hundred and twenty-three children were admitted to hospital with a diagnosis of severe malaria, with 64 in control areas and 59 in SMC areas, showing a reduction in the incidence rate of severe disease of 45% (95% CI 5%–68%, p = 0.031). Estimates of the reduction in the prevalence of parasitaemia at the end of the transmission season in SMC areas were 68% (95% CI 35%–85%) p = 0.002 in 2008, 84% (95% CI 58%–94%, p < 0.001) in 2009, and 30% (95% CI -130%–79%, p = 0.56) in 2010. SMC was well tolerated with no serious adverse reactions attributable to SMC drugs. Vomiting was the most commonly reported mild adverse event but was reported in less than 1% of treatments. The average cost of delivery was US$0.50 per child per month, but varied widely depending on the size of the health post. Limitations included the low rate of mortality, which limited our ability to detect an effect on this endpoint. Conclusions SMC substantially reduced the incidence of outpatient cases of malaria and of severe malaria in children, but no difference in all-cause mortality was observed. Introduction of SMC was associated with an overall reduction in malaria incidence in untreated age groups. In many areas of Africa with seasonal malaria, there is a substantial burden in older children that could be prevented by SMC. SMC in older children is well tolerated and effective and can contribute to reducing malaria transmission. Trial Registration ClinicalTrials.gov NCT00712374, In a stepped-wedge cluster-randomized trial, Paul J. Milligan and colleagues determine the effectiveness of SMC in Senegalese children up to ten years of age., Author Summary Why was this study done? SMC was originally intended for children under five years of age. In many areas of the sub-Sahel, there is a substantial burden of malaria in older children; this may justify extending the age range of SMC. This study was done in central Senegal to evaluate the effectiveness of SMC when given to children up to ten years of age. What did the researchers do and find? SMC was introduced into the area served by 54 health posts by district health teams over three years using a randomised stepped-wedge design. Malaria cases were detected at outpatient clinics and in hospitals, and deaths were recorded through a demographic surveillance system. SMC reduced the incidence of malaria in children up to ten years of age by 60%. No reduction in all-cause child deaths was observed, but the incidence of severe malaria was reduced by 45%. SMC administered to children up to ten years of age led to a reduction in malaria incidence in older age groups by 26%. What do these findings mean? SMC given to children up to ten years of age is highly effective in preventing malaria in children and can contribute to reducing overall malaria transmission. SMC programmes have started in 11 countries. In many of these countries, there is a substantial burden of malaria in older children. The findings of this study indicate that a much greater impact could be achieved by extending the age range of SMC.

BACKGROUND: Home-based management of malaria (HMM) may improve access to diagnostic testing and treatment with artemisinin combination therapy (ACT). In the Sahel region, seasonal malaria chemoprevention (SMC) is now recommended for the prevention of malaria in children. It is likely that combinations of antimalarial interventions can reduce the malaria burden. This study assessed the feasibility, effectiveness and safety of combining SMC and HMM delivered by community health workers (CHWs). METHODS: A cluster-randomised trial was carried out during two transmission seasons in eight villages located in the south-eastern part of Senegal. Intervention communities received HMM+SMC while control communities received HMM. Primary end point was the incidence of malaria attacks during the follow up period. Secondary end points included: malaria diagnostic accuracy; access to ACT treatment; SMC coverage; safety and drug tolerability. RESULTS: The adjusted rate ratio for incidence of malaria attacks in intervention and control communities was 0.15, indicating a protective effect of HMM+SMC of 85% (95% CI: 39.9-96.3%, p=0.01). Access to ACT treatment was 96.4% while SMC coverage represented 97.3% (95% CI: 91.3-100%) in 2010, and 88.8% (95% CI: 84.2-93.6%) in 2011. No serious adverse events were recorded. CONCLUSION: It seems feasible and safe to combine SMC with HMM intervention, while achieving high coverage and effectiveness of both SMC and HMM. TRIAL REGISTRATION: (www.pactr.org) PACTR201305000551876.

Aedes mosquitoes are the major vectors of (re)-emerging infections including arboviruses (dengue, Chikungunya, yellow fever) in developing countries. Moreover, the emergence of Aedes-borne diseases in the developed world is currently a source of concern. Evaluation of human immune responses to Aedes bites could be a useful immuno-epidemiological tool for evaluating exposure to Aedes-borne diseases and thus predicting the risk of such emerging diseases. Specific IgE and IgG4 antibody (Ab) responses to Aedes aegypti saliva were evaluated in young Senegalese children living in an area of exposure to the Aedes vector. Specific IgE and IgG4 responses increased during rainy season of high exposure to Aedes bites. In addition, the evolution of anti-saliva isotype levels during the rainy season presented spatial heterogeneity between the studied villages. These preliminaries results support the potential approach of using anti-saliva Ab responses for evaluating exposure to Aedes vectors and risks of emerging arbovirus infections.

Negative consequences of malaria might account for seasonality in nutritional status in children in the Sahel. We report the impact of a randomized, double-blind, placebo-controlled trial of seasonal intermittent preventive anti-malarial treatment on growth and nutritional status in 1,063 Senegalese preschool children. A combination of artesunate and sulfadoxine-pyrimethamine was given monthly from September to November. In the intervention arm, mean weight gain was significantly greater (122.9 ± 340 versus 42.9 ± 344 [SD] g/mo, P < 0.0001) and losses in triceps and subscapular skinfold measurements were less (−0.39 ± 1.01 versus −0.66 ± 1.01 mm/mo, and −0.15 ± 0.64 versus −0.36 ± 0.62 mm/mo, respectively, P < 0.0001 for both). There was no difference in height increments. The prevalence of wasting increased significantly in the control arm (4.6% before versus 9.5% after, P < 0.0001), but remained constant in intervention children: 5.6% versus 7.0% (P = 0.62). The prevention of malaria would improve child nutritional status in areas with seasonal transmission.

Background Long-acting artemisinin-based combination therapy (LACT) offers the potential to prevent recurrent malaria attacks in highly exposed children. However, it is not clear where this advantage will be most important, and deployment of these drugs is not rationalized on this basis. Methods To understand where post-treatment prophylaxis would be most beneficial, the relationship between seasonality, transmission intensity and the interval between malaria episodes was explored using data from six cohort studies in West Africa and an individual-based malaria transmission model. The total number of recurrent malaria cases per 1000 child-years at risk, and the fraction of the total annual burden that this represents were estimated for sub-Saharan Africa. Results In settings where prevalence is less than 10 %, repeat malaria episodes constitute a small fraction of the total burden, and few repeat episodes occur within the window of protection provided by currently available drugs. However, in higher transmission settings, and particularly in high transmission settings with highly seasonal transmission, repeat malaria becomes increasingly important, with up to 20 % of the total clinical burden in children estimated to be due to repeat episodes within 4 weeks of a prior attack. Conclusion At a given level of transmission intensity and annual incidence, the concentration of repeat malaria episodes in time, and consequently the protection from LACT is highest in the most seasonal areas. As a result, the degree of seasonality, in addition to the overall intensity of transmission, should be considered by policy makers when deciding between ACT that differ in their duration of post-treatment prophylaxis. Electronic supplementary material The online version of this article (doi:10.1186/s12936-015-0839-4) contains supplementary material, which is available to authorized users.

Fraction of all malaria episodes that occur within 28, 42, 56 and 70Â days of a previous episode. Proportion of all malaria episodes that occur within 28, 42, 56 and 70Â days of a previous episode, according to seasonality and transmission intensity.

Total malaria burden per 1,000 children in different intervals after the preceding episode. Burden of repeat malaria per 1,000 children occurring in different intervals following the previous episode, according to the Markham seasonality index (MSI). Scenarios shown for 20, 40 and 60Â % prevalence.

Sites with bimodal malaria transmission. Description of how sites with bimodal malaria transmission were identified, their location in Africa, an example results for 2 scenarios of bimodal transmission.

Details of the Markham Seasonality Index. Explanation of how the Markham Seasonality Index is calculated, and illustration of two example scenarios.

Markham seasonality index of clinical malaria incidence for the six studies in West Africa. Graphical representation of the Markham Seasonality Index for the 6 studies in West Africa.

Seasonality profiles for first administrative units at 10Â % intervals of Markham Seasonality Index. Seasonality in larval carrying capacity (ability of environment to support development of mosquito larvae) for sites representing 10Â % intervals of the Markham Seasonality Index.

Distribution of interval between malaria episodes according to prevalence and seasonality in transmission. Distribution of intervals between malaria episodes for each of the 45 scenarios modelled.

Markham Seasonality Polygons for the first admin units representing 10Â % intervals of Markham index. Graphical representation of the Markham Seasonality Index for the sites representing 10Â % intervals of the Markham Seasonality Index.

Correlation between model seasonality in larval carrying capacity and predicted seasonality in clinical malaria. Correlation between Markham seasonality index calculated for the larval carrying capacity function (as an input into the model determining seasonality) and MSI for seasonality in clinical malaria at different levels of prevalence.

Seasonal malaria chemoprevention (SMC) is defined as the intermittent administration of full treatment courses of an antimalarial drug to children during the peak of malaria transmission season with the aim of preventing malaria-associated mortality and morbidity. SMC using sulfadoxine-pyrimethamine (SP) combined with amodiaquine (AQ) is a promising strategy to control malaria morbidity in areas of highly seasonal malaria transmission. However, a concern is whether SMC can delay the natural acquisition of immunity toward malaria parasites in areas with intense SMC delivery. To investigate this, total IgG antibody (Ab) responses to Plasmodium falciparum antigens glutamate-rich protein R0 (GLURP-R0) and apical membrane antigen 1 (AMA-1) were measured by enzyme-linked immunosorbent assay in Senegalese children under the age of 10 years in 2010 living in Saraya and Velingara districts (with SMC using SP + AQ [SMC+] since 2007) and Tambacounda district (without SMC (SMC-)). For both P. falciparum antigens, total IgG response were significantly higher in the SMC- compared with the SMC+ group (for GLURP-R0, P < 0.001 and for AMA-1, P = 0.001). There was as well a nonsignificant tendency for higher percentage of positive responders in the SMC- compared with the SMC+ group (for GLURP-R0: 22.2% versus 14.4%, respectively [P = 0.06]; for AMA-1: 45.6% versus 40.0%, respectively [P = 0.24]). Results suggest that long-term malaria chemoprevention by SMC/SP + AQ have limited impact on the development of acquired immunity, as tested using the P. falciparum antigens GLURP-R0 and AMA-1. However, other factors, not measured in this study, may interfere as well.

Background Malaria is major public health problem in Senegal. In some parts of the country, it occurs almost permanently with a seasonal increase during the rainy season. There is evidence to suggest that the prevalence of malaria in Senegal has decreased considerably during the past few years. Recent data from the Senegalese National Malaria Control Programme (NMCP) indicates that the number of malaria cases decrease from 1,500,000 in 2006 to 174,339 in 2010. With the decline of malaria morbidity in Senegal, the characterization of the new epidemiological profile of this disease is crucial for public health decision makers. Methods SaTScan™ software using the Kulldorf method of retrospective space-time permutation and the Bernoulli purely spatial model was used to identify malaria clusters using confirmed malaria cases in 74 villages. ArcMAp was used to map malaria hotspots. Logistic regression was used to investigate risk factors for malaria hotspots in Keur Soce health and demographic surveillance site. Results A total of 1,614 individuals in 440 randomly selected households were enrolled. The overall malaria prevalence was 12%. The malaria prevalence during the study period varied from less than 2% to more than 25% from one village to another. The results showed also that rooms located between 50 m to 100 m away from livestock holding place [adjusted O.R = 0.7, P = 0.044, 95% C.I (1.02 - 7.42)], bed net use [adjusted O.R = 1.2, P = 0.024, 95% C.I (1.02 –1.48)], are good predictors for malaria hotspots in the Keur Soce health and demographic surveillance site. The socio economic status of the household also predicted on hotspots patterns. The less poor household are 30% less likely to be classified as malaria hotspots area compared to the poorest household [adjusted O.R = 0.7, P = 0.014, 95% C.I (0.47 – 0.91)]. Conclusion The study investigated risk factors for malaria hotspots in small communities in the Keur Soce site. The result showed considerable variation of malaria prevalence between villages which cannot be detected in aggregated data. The data presented in this paper are the first step to understanding malaria in the Keur Soce site from a micro-geographic perspective.

Ruel and Menon recently published a young child feeding index based on characteristics taken from 24-h and 7-d recalls. A strong positive association was found in 7 Latin American Demographic and Health Surveys for 12- to 36-mo-old children (1). The aim of this study was to test for associations of this index with height-for-age and linear growth in African children. Children (n = 500), aged 12-42 mo, living in a rural area of Senegal were visited in their homes in April-May, and 24-h and 7-d food recalls were conducted with their mothers. Height was measured, and measurements taken 7 mo earlier were used to compute linear growth rates. General linear models were used to adjust for potential confounders (child age and sex, maternal height, BMI, and socioeconomic status). The feeding index was not associated with either height-for-age (adjusted means: -1.01, -1.06, and -1.20 Z-scores for the 1st, 2nd, and 3rd tercile, respectively) or with linear growth (6.2, 6.0, and 6.3 cm/7 mo for the 3 terciles, respectively). Continuing breast-feeding was negatively associated with height-for-age (P < 0.05) and positively associated with linear growth (P < 0.01). Frequent consumption of fruit was positively associated with both (P = 0.059 and P = 0.027, respectively, in adjusted models), whereas food consumption from an animal source was not. In conclusion, the composite feeding index was independent of height and linear growth in these rural African children, due in part to reverse causality between breast-feeding duration and stunting.

Background: It has been assumed that measles infection may be associated with persistent immune suppression and long-term excess mortality. However, few community studies of mortality after measles infection have been carried out. We examined long-term mortality for measles cases, sub-clinical measles cases, and uninfected contacts after an epidemic in rural Senegal. Methods: The study was carried out in Niakhar, a rural area of Senegal. Index cases of measles were identified and children less than 7 years of age exposed to measles in the same compound had acute and convalescent blood samples collected. Clinically diagnosed measles cases were serologically confirmed. Children without clinical symptoms were classified as sub-clinical cases if they had a four-fold or greater change in antibody levels between samples collected at exposure and 1 month later and as uninfected if there was no or a two-fold change in antibody levels. Results: There were 31 index cases, and among 184 exposed contacts, 35 (19%) children developed clinical measles. Among contacts that did not develop clinical measles, 45% had sub-clinical infection. Measles cases, sub-clinical cases, and uninfected contacts did not differ with respect to nutritional status. However, uninfected children without clinical symptoms and change in antibody level had higher initial measles specific IgG antibody levels and less intensive exposure to the index case. No index or secondary case of measles died in the acute phase of infection nor did any of the children exposed to measles die in the first 2 months after exposure. Exposed children developing clinical measles had lower age-adjusted mortality over the next 4 years than exposed children who did not develop clinical measles (P

Background Recent global estimates show that P. falciparum malaria still constitutes an enormous public health concern. Chief amongst desirable interventions is an effective vaccine that could complement existing control measures. Heterologous prime-boost vaccinations involving chimpanzee adenovirus 63 (ChAd63) and modified vaccinia Ankara (MVA) encoding ME-TRAP have consistently shown acceptable safety, excellent immunogenicity and substantial efficacy in African adult and paediatric populations. When licensed, malaria vaccines would preferably be given to infants receiving routine childhood immunisations. Nevertheless, no studies have evaluated the interference of ChAd63/MVA ME-TRAP when co-administered with routine Expanded Programme Immunisation (EPI) vaccines. Methods We enrolled 65 Gambian infants and neonates in an age de-escalating fashion, priming at 4 months, 8 weeks or 1 week of age, and randomised them to vaccine or control (EPI vaccines only) arm. Safety was assessed by the description of vaccine-related adverse events ascertained through clinical assessments, biochemical and haematological tests. Immunogenicity was evaluated by IgG ELISA, interferon-gamma ELISPOT, intra-cellular cytokine staining and flow cytometry. Antibody testing was performed to assess any interference of the EPI vaccines with responses to ChAd63/MVA ME-TRAP. Results Overall, the vaccination regimes were well tolerated in all age groups with no vaccine-related serious adverse events. High level IgG and antigen-specific T cell responses were generated after boosting with MVA, with T cell responses highest in the infants 8 week old at priming dose. EPI vaccines retained unchanged antibody levels in all age groups. Conclusions Potent humoral and cellular immunity induced by heterologous prime-boost immunisation with ChAd63 and MVA ME-TRAP did not interfere with the immunogenicity of co-administered routine EPI vaccines in infants and neonates. Potent T cell induction was again observed with the vectored malaria vaccines despite co-administration with EPI vaccines.

Background: Several of the intended P. falciparum vaccine candidate antigens are highly polymorphic and could render a vaccine ineffective if their antigenic sites were not represented in the vaccine. This study aimed to characterize genetic diversity of vaccine candidate antigens merozoite surface protein-3 (MSP-3), apical membrane antigen-1 (AMA-1) and erythrocyte binding antigen (EBA-175) in P. falciparum isolates from Senegal. Methods: DNA analysis was completed on 170 isolates of P. falciparum collected from Keur Soce in Senegal between 2006 and 2008. Genetic diversity was determined in the three P. falciparum genes by, PCR followed by restriction fragment length polymorphism (RFLP). Results: From 170 samples collected, successful, PCR products were obtained from 135 (79%), 140 (82%) and 128 (75%) for AMA-1, MSP-3 and EBA-175, respectively. The results showed that the EBA-175 gene presented 4 different alleles [EBA-175F_loop (62.3%), EBA-175C_loop (46.1%), EBA-175~400bp (17.6%), EBA-175~360bp (8.4%)]. Regarding the MSP-3 patterns, the analysis revealed the presence of three alleles MSP-3_K1 (49.2%), MSP-3_3D7 (54.2%) and MSP-3~350bp (15%). For AMA-1, the results showed three different alleles AMA-1_K1 (39%), AMA-1_HB3 (33%), AMA-1_3D7 (32%). Conclusion: Characterization of the genetic diversity in Plasmodium isolates from Keur Soce in Senegal in the three genes investigated showed a high degree of polymorphism. These findings are helpful in the formulation of a vaccine considering restricted repertoire populations.

It has been suggested that measles infection mainly kills frail children who are likely to die anyhow of other infections. If that were true, the proportion of frail children should increase after the introduction of measles vaccination and post-measles mortality compared with mortality in uninfected children should increase when the case fatality declines and frail children are no longer dying of measles. The latter deduction was investigated in Niakhar, Senegal, where the measles case fatality has declined markedly. Measles has been studied in Niakhar during 12 years from 1983 to 1994. We compared long-term mortality after measles infection in periods with both high and low case fatality. The acute measles case fatality rate (CFR) declined from 6.5% in 1983–1986 to 1.5% in 1987–1994, an age-adjusted decline of 66% (RR=0.34 (0.19–0.58)). Between 1983–1986 and 1987–1994, mortality in the first year after measles infection declined by 35% (RR=0.65 (0.37–1.16)), the pattern being the same in the second and third year after infection (RR=0.63 (0.33–1.21)). This reduction could not be related to introduction of immunization, treatment of measles with Vitamin A, or prophylactic use of antibiotics. Controlling for age, immunization, and season, the decline in post-measles mortality was similar to the fall in non-measles-related mortality between the two periods (mortality rate ratio=0.72 (0.64–0.80)). Since the mortality decline in survivors of measles was as large as the decline in mortality among uninfected children, reduction in acute measles mortality did not lead to accumulation of frail children. We doubt measles infection ever eliminated mainly weak children; it always killed a broad spectrum of children, most of whom were “fit to survive”. Hence, it seems unlikely that measles vaccination has contributed to the survival of more frail children.

Background Community case management of malaria (CCMm) and seasonal malaria chemoprevention (SMC) are anti-malarial interventions that can lead to substantial reduction in malaria burden acting in synergy. However, little is known about the social acceptability of these interventions. A study was undertaken to assess whether combining the interventions would be an acceptable approach to malaria control for community health workers (CHWs). Methods Sixty-one interviews and six focus group discussions were conducted nested in a cluster-randomized trial assessing the impact of combining CCMm and SMC in a rural area of Senegal. Participants consisted of: (i) members of village associations, (ii) members of families who had access to the interventions as well as members of families who did not access the interventions, (iii) CHWs, and (iv) community leaders, e g, religious guides and village chiefs. Results The interventions were acceptable to the local population and perceived as good strategy to make health care services available to community members and thus, to reduce the delays in access to anti-malarial treatment as well as expenses related to patients’ transfer to the health post. The use of malaria rapid diagnostic test (RDT) contributed to improving CHWs diagnostic capacity as well as malaria treatment practices. Study participants notified RDT and drugs stock-out as the major risk for sustainability of the intervention at community level. Conclusion Combining CCMm and SMC is a well accepted, community-based approach that can contribute to control malaria in areas where malaria transmission is seasonal.

BACKGROUND: In sub-Saharan Africa, malaria is the leading cause of morbidity and mortality especially in children. In Senegal, seasonal malaria chemoprevention (SMC) previously referred to as intermittent preventive treatment in children (IPTc) is a new strategy for malaria control in areas of high seasonal transmission. An effectiveness study of SMC, using sulphadoxine-pyrimethamine (SP) plus amodiaquine (AQ), was conducted in central Senegal from 2008 to 2010 to obtain information about safety, feasibility of delivery, and cost effectiveness of SMC. Here are report the effect of SMC delivery on the prevalence of markers of resistance to SP and AQ. METHODS: This study was conducted in three health districts in Senegal with 54 health posts with a gradual introduction of SMC. Three administrations of the combination AQ + SP were made during the months of September, October and November of each year in children aged less than 10 years living in the area. Children were surveyed in December of each year and samples (filter paper and thick films) were made in 2008, 2009 and 2010. The prevalence of mutations in the pfdhfr, pfdhps, pfmdr1 and pfcrt genes was investigated by sequencing and RTPCR in samples positive by microscopy for Plasmodium falciparum. RESULTS: Mutations at codon 540 of pfdhps and codon 164 of pfdhfr were not detected in the study. Among children with parasitaemia at the end of the transmission seasons, the CVIET haplotypes of pfcrt and the 86Y polymorphism of pfmdr1 were more common among those that had received SMC, but the number of infections detected was very low and confidence intervals were wide. The overall prevalence of these mutations was lower in SMC areas than in control areas, reflecting the lower prevalence of parasitaemia in areas where SMC was delivered. CONCLUSION: The sensitivity of P. falciparum to SMC drugs should be regularly monitored in areas deploying this intervention. Overall the prevalence of genotypes associated with resistance to either SP or AQ was lower in SMC areas due to the reduced number of parasitaemia individuals.

BACKGROUND: Despite recent advances in malaria diagnosis and treatment, many isolated communities in rural settings continue to lack access to these life-saving tools. Community-case management of malaria (CCMm), consisting of lay health workers (LHWs) using malaria rapid diagnostic tests (RDTs) and artemisinin-based combination therapy (ACT) in their villages, can address this disparity. METHODS: This study examined routine reporting data from a CCMm programme between 2008 and 2011 in Saraya, a rural district in Senegal, and assessed its impact on timely access to rapid diagnostic tests and ACT. RESULTS: There was a seven-fold increase in the number of LHWs providing care and in the number of patients seen. LHW engagement in the CCM programme varied seasonally, 24,3% of all patients prescribed an ACT had a negative RDT or were never administered an RDT, and less than half of patients with absolute indications for referral (severe symptoms, age under two months and pregnancy) were referred. There were few stock-outs. DISCUSSION: This CCMm programme successfully increased the number of patients with access to RDT and ACT, but further investigation is required to identify the cause for over-prescription, and low rates of referrals for patients with absolute indications. In contrast, previous widespread stock-outs in Saraya's CCMm programme have now been resolved. CONCLUSION: This study demonstrates the potential for CCMm programmes to substantially increase access to life-saving malarial diagnostics and treatment, but also highlights important challenges in ensuring quality.

Sulfadoxine-pyrimethamine with amodiaquine (SP-AQ) is a highly efficacious regimen for intermittent preventive treatment to prevent malaria in children (IPTc), but the amodiaquine component is not always well tolerated. We determined the association between amodiaquine dosage by body weight and mild adverse events (AEs) and investigated whether alternative age-based regimens could improve dosing accuracy and tolerability, using data from two trials of IPTc in Senegal, one in which AQ dose was determined by age and the other in which it was determined by weight category. Both dosage strategies resulted in some children receiving AQ doses above the recommended therapeutic range. The odds of vomiting increased with increasing amodiaquine dosage. In one study, incidence of fever also increased with increasing dosage. Anthropometric data from 1,956 children were used to predict the dosing accuracy of existing and optimal alternative regimens. Logistic regression models describing the probability of AEs by dosage were used to predict the potential reductions in mild AEs for each regimen. Simple amendments to current AQ dosing schedules based on the child's age could substantially increase dosing accuracy and thus improve the tolerability of IPTc using SP-amodiaquine in situations where weighing the child is impractical.

Background Intermittent preventive treatment in children (IPTc) is a promising strategy to control malaria morbidity. A significant concern is whether IPTc increases children's susceptibility to subsequent malaria infection by altering their anti-Plasmodium acquired immunity. Methods To investigate this concern, IgG antibody (Ab) responses to Plasmodium falciparum schizont extract were measured in Senegalese children (6 months-5 years old) who had received three rounds of IPTc with artesunate + sulphadoxine-pyrimethamine (or placebo) at monthly intervals eight months earlier. Potential confounding factors, such as asexual malaria parasitaemia and nutritional status were also evaluated. Results Firstly, a bivariate analysis showed that children who had received IPTc had lower anti-Plasmodium IgG Ab levels than the non-treated controls. When epidemiological parameters were incorporated into a multivariate regression, gender, nutritional status and haemoglobin concentration did not have any significant influence. In contrast, parasitaemia, past malaria morbidity and increasing age were strongly associated with a higher specific IgG response. Conclusions The intensity of the contacts with P. falciparum seems to represent the main factor influencing anti-schizont IgG responses. Previous IPTc does not seem to interfere with this parasite-dependent acquired humoral response eight months after the last drug administration.

Background In sub-Saharan Africa, preschool children represent the population most vulnerable to malaria and malnutrition. It is widely recognized that malnutrition compromises the immune function, resulting in higher risk of infection. However, very few studies have investigated the relationship between malaria, malnutrition and specific immunity. In the present study, the anti-Plasmodium falciparum IgG antibody (Ab) response was evaluated in children according to the type of malnutrition. Methods Anthropometric assessment and blood sample collection were carried out during a cross-sectional survey including rural Senegalese preschool children. This cross-sectional survey was conducted in July 2003 at the onset of the rainy season. Malnutrition was defined as stunting (height-for-age P. falciparum whole extracts (schizont antigens) was assessed by ELISA in sera of the included children. Results Both the prevalence of anti-malarial immune responders and specific IgG Ab levels were significantly lower in malnourished children than in controls. Depending on the type of malnutrition, wasted children and stunted children presented a lower specific IgG Ab response than their respective controls, but this difference was significant only in stunted children (P = 0.026). This down-regulation of the specific Ab response seemed to be explained by severely stunted children (HAZ ≤ -2.5) compared to their controls (P = 0.03), while no significant difference was observed in mildly stunted children (-2.5 < HAZ P. falciparum Ab response appeared to be independent of the intensity of infection. Conclusion Child malnutrition, and particularly stunting, may down-regulate the anti-P. falciparum Ab response, both in terms of prevalence of immune responders and specific IgG Ab levels. This study provides further evidence for the influence of malnutrition on the specific anti-malarial immune response and points to the importance of taking into account child malnutrition in malaria epidemiological studies and vaccine trials.

Background The long terminal half life of piperaquine makes it suitable for intermittent preventive treatment for malaria but no studies of its use for prevention have been done in Africa. We did a cluster randomized trial to determine whether piperaquine in combination with either dihydroartemisin (DHA) or sulfadoxine-pyrimethamine (SP) is as effective, and better tolerated, than SP plus amodiaquine (AQ), when used for intermittent preventive treatment in children delivered by community health workers in a rural area of Senegal. Methods Treatments were delivered to children 3–59 months of age in their homes once per month during the transmission season by community health workers. 33 health workers, each covering about 60 children, were randomized to deliver either SP+AQ, DHA+PQ or SP+PQ. Primary endpoints were the incidence of attacks of clinical malaria, and the incidence of adverse events. Results 1893 children were enrolled. Coverage of monthly rounds and compliance with daily doses was similar in all groups; 90% of children received at least 2 monthly doses. Piperaquine combinations were better tolerated than SP+AQ with a significantly lower risk of common, mild adverse events. 103 episodes of clinical malaria were recorded during the course of the trial. 68 children had malaria with parasitaemia >3000/µL, 29/671 (4.3%) in the SP+AQ group, compared with 22/604 (3.6%) in the DHA+PQ group (risk difference 0.47%, 95%CI −2.3%,+3.3%), and 17/618 (2.8%) in the SP+PQ group (risk difference 1.2%, 95%CI −1.3%,+3.6%). Prevalences of parasitaemia and the proportion of children carrying Pfdhfr and Pfdhps mutations associated with resistance to SP were very low in all groups at the end of the transmission season. Conclusions Seasonal IPT with SP+PQ in children is highly effective and well tolerated; the combination of two long-acting drugs is likely to impede the emergence of resistant parasites. Trial Registration ClinicalTrials.gov NCT00529620