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Anopheles gambiae and Anopheles coluzzii, often found in sympatry and synchronous, have undergone a premating reproductive isolation across their distribution range. However, in the Western coast of Africa, unexpected hybridization zones have been observed, and little is known about swarming behavior of these cryptic taxa. Here, we characterized the swarming behavior of An. coluzzii and An. gambiae to investigate its role in the high hybridization level in Senegal. The study was conducted in the south and central Senegal during the 2018 rainy season. Mating swarms of malaria vectors were surveyed at sunset and collected using an insect net. Meanwhile, indoor resting populations of malaria vectors were collected by pyrethrum spray catches. Upon collection, specimens were identified morphologically, and then members of the An. gambiae complex were identified at the species level by polymerase chain reaction (PCR). An. gambiae swarmed mainly over bare ground, whereas An. coluzzii were found swarming above various objects creating a dark-light contrast with the bare ground. The swarms height varied from 0.5 to 2.5 m. Swarming starting time was correlated with sunset whatever the months for both species, and generally lasted about 10 min. No mixed swarm of An. gambiae and An. coluzzii was found even in the high hybridization area. These results indicated a premating isolation between An. coluzzii and An. gambiae. However, the high hybridization rate in the sympatric area suggests that heterogamous mating is occurring, thus stressing the need for further extensive studies., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Understanding the behavior and ecology of local malaria vectors is essential for the effectiveness of the commonly used vector-targeted malaria control tools in areas of low malaria transmission. This study was conducted to determine species composition, biting behavior and infectivity of the major Anopheles vectors of Plasmodium falciparum in low transmission settings in central Senegal. Adult mosquitoes were collected using human landing catches during 2 consecutive nights and Pyrethrum Spray Catches in 30-40 randomly selected rooms, from July 2017 to December 2018 in 3 villages. Anopheline mosquitoes were morphologically identified using conventional keys; their reproductive status assessed by ovary dissections, and a sub-sample of Anopheles gambiae s.l. were identified to species level using polymerase chain reaction (PCR). Plasmodium sporozoite infections were detected using real-time quantitative PCR. During this study 3684 Anopheles were collected of which 97% were An. gambiae s.l., 0.6% were Anopheles funestus, and 2.4% were Anopheles pharoensis. Molecular identification of 1,877 An. gambiae s.l. revealed a predominance of Anopheles arabiensis (68.7%), followed by Anopheles melas (28.8%), and Anopheles coluzzii (2.1%). The overall human-biting rate of An. gambiae s.l. was highest in the inland site of Keur Martin with 4.92 bites per person per night, while it was similar in the deltaic site, Diofior (0.51) and the coastal site, Mbine Coly (0.67). Parity rates were similar in An. arabiensis (45%) and An. melas (42%). Sporozoite infections were detected in both An. arabiensis and An. melas with the respective infection rates of 1.39% (N = 8) and 0.41% (N = 1). Results suggest that low residual malaria in central Senegal is transmitted by An. arabiensis and An. melas. Consequently, both vectors will need to be targeted as part of malaria elimination efforts in this area of Senegal., (© The Author(s) 2023. Published by Oxford University Press on behalf of Entomological Society of America.)

Background: Despite the introduction of efficacious interventions for malaria control, sub-Saharan Africa continues to bear the highest burden of malaria and its associated effects on vulnerable populations, such as pregnant women and children. This meta-ethnographic review contributes to literature on malaria in pregnancy interventions in sub-Saharan Africa by offering insights into the multiple factors that motivate or demotivate women from accessing MiP interventions., Methods: A meta-ethnographic approach was used for the synthesis. Original qualitative research articles published from 2010 to November 2021 in English in sub-Saharan Africa were searched for. Articles focusing on WHO's recommended interventions such as intermittent preventive treatment with sulfadoxine-pyrimethamine, long-lasting insecticidal nets and testing and treatment of Malaria in Pregnancy (MiP) were included. Selected articles were uploaded into Nvivo 11 for thematic coding and synthesis., Results: Twenty-seven original qualitative research articles were included in the analysis. Main factors motivating uptake of MiP interventions were: (1) well organized ANC, positive attitudes of health workers and availability of MiP services; (2) Women's knowledge of the effects of malaria in pregnancy, previous experience of accessing responsive ANC; (3) financial resources and encouragement from partners, relatives and friends and (4) favourable weather condition and nearness to a health facility. Factors that demotivated women from using MiP services were: (1) stock-outs, ANC charges and health providers failure to provide women with ample education on the need for MiP care; (2) perception of not being at risk and the culture of self-medication; (3) fear of being bewitched if pregnancy was noticed early, women's lack of decision-making power and dependence on traditional remedies and (4) warm weather, long distances to health facilities and the style of construction of houses making it difficult to hang LLINs., Conclusions: Health system gaps need to be strengthened in order to ensure that MiP interventions become accessible to women. Additionally, health managers need to involve communities in planning, designing and implementing malaria interventions for pregnant women. It is important that the health system engage extensively with communities to facilitate pregnant women and communities understanding of MiP interventions and the need to support pregnant women to access them., (© 2022. The Author(s).)

In the central western Senegal, malaria transmission has been reduced low due to the combination of several effective control interventions. However, despite this encouraging achievement, residual malaria transmission still occurring in few areas, mainly ensured by An. arabiensis and An. melas. The resurgence or the persistence of the disease may have originated from the increase and the spread of insecticide resistance genes among natural malaria vectors populations. Therefore, assessing the status and mechanisms of insecticides resistance among targeted malaria vectors is of highest importance to better characterize factors underlying the residual transmission where it occurs. Malaria vectors were collected from three selected villages using nocturnal human landing catches (HLC) and pyrethrum spray collections (PSC) methods. An. gambiae s.l. specimens were identified at the species level then genotyped for the presence of kdr-west (L1014F), kdr-east (L1014S) and ace-1 R mutations by qPCR. An. arabiensis (69.36%) and An. melas (27.99%) were the most common species of the Gambiae complex in the study area. Among An. arabiensis population, the allelic frequency of the kdr-east (22.66%) was relatively higher than for kdr-west mutation (9.96%). While for An. melas populations, the overall frequencies of both mutations were very low, being respectively 1.12% and 0.40% for the L1014S and L1014F mutations. With a global frequency of 2%, only the heterozygous form of the G119S mutation was found only in An. arabiensis and in all the study sites. The widespread occurrence of the kdr mutation in both An. arabiensis and An. melas natural populations, respectively the main and focal vectors in the central-western Senegal, may have contributed to maintaining malaria transmission in the area. Thus, compromising the effectiveness of pyrethroids-based vector control measures and the National Elimination Goal. Therefore, monitoring and managing properly insecticide resistance became a key programmatic intervention to achieve the elimination goal where feasible, as aimed by Senegal. Noteworthy, this is the first report of the ace-1 mutation in natural populations of An. arabiensis from Senegal, which need to be closely monitored to preserve one of the essential insecticide classes used in IRS to control the pyrethroids-resistant populations., (Copyright © 2021. Published by Elsevier Inc.)

Despite the deployment of several effective control interventions in central-western Senegal, residual malaria transmission is still occurring in some hotspots. To better tailor targeted control actions, it is critical to unravel the underlying environmental and geographical factors that cause the persistence infection in hotspot villages. "Hotspots villages" were defined in our study as those reporting more than six indigenous malaria cases during the previous year. A total of ten villages, including seven hotspots and three non-hotspots, were surveyed. All potential mosquito breeding sites identified in and around the ten study villages were regularly monitored between 2013 and 2017. Monitoring comprised the detection of anopheline larvae and the collection of epidemiological, hydrogeological, topographical, and biogeographical data. The number of larval breeding sites described and monitored during the study period ranged from 50 to 62. Breeding sites were more numerous in hotspot sites in each year of monitoring, with 90.3% (56/62) in 2013, 90.9% (50/55) in 2014, 90.3% (56/62) in 2015 and 86% (43/50) in 2017 (Fisher exact test; p = 1). In the non-hotspot areas, the data for the same years were, respectively, 9.7% (6/62), 9.1% (5/55), 9.7% (6/62) and 14% (7/50) (p = 1). The Hotspot villages were characterized mostly by saline or moderately saline hydro-morphic and halomorphic soils allowing water retention and a potential larval breeding sites. By contrast, non-hotspot villages were characterized mainly by a high proportion of extremely permeable sandy-textured soils, which due to their porosity had low water retention. The annual number of confirmed malaria cases was correlated with the frequency and extent of breeding sites. Malaria cases were significantly more frequent in the hamlets located near breeding sites of An. gambiae s.l., gradually decreasing with increasing remoteness. This study shows that the characteristics of larval breeding sites, as measured by their longevity, stability, proximity to human habitation, and their positivity in Anopheles larvae are likely determining factors in the persistence of malaria hotspots in central-western Senegal. The results of this study shed more light on the environmental factors underlying the residual transmission and should make it possible to better target vector control interventions for malaria elimination in west-central Senegal., Competing Interests: The authors have declared that no competing interests exist.

Several efforts are being made now for malaria elimination with a goal for eradication. New tools and strategies are being developed and there is currently renewed political engagement and interest. Several technical groups have produced a guide on elimination for policymakers and indicated different research questions to be addressed. The World Health Assembly resolution and the United Nations General Assembly convened a high-level roundtable "From High Burden to High Impact: Getting back on track to end Malaria". In Africa, the Head of states pronounced a vision for an Africa free of malaria and launched the slogan "Zero malaria starts with me". Massive efforts to sustain research capacity in the endemic countries will be critical. It will be important to both increase domestic financing, and advocate to sustain and increase funding from major donor countries. It is unethical to continue to observe deaths of so many children in malaria endemic countries, the most vulnerable populations. Considering malaria eradication as a vision and working with all the opportunities we now have could accelerate the process. Eliminating malaria with a country regional approach and progressing step by step will give us consistent information on our way towards eradication.

Background: Seasonal malaria chemoprevention (SMC) is recommended in the Sahel region of Africa for children under 5 years of age, for up to 4 months of the year. It may be appropriate to include older children, and to provide protection for more than 4 months. We evaluated the effectiveness of SMC using sulfadoxine-pyrimethamine plus amodiaquine given over 5 months to children under 10 years of age in Saraya district in south-east Senegal in 2011., Methods and Findings: Twenty-four villages, including 2,301 children aged 3-59 months and 2,245 aged 5-9 years, were randomised to receive SMC with community case management (CCM) (SMC villages) or CCM alone (control villages). In all villages, community health workers (CHWs) were trained to treat malaria cases with artemisinin combination therapy after testing with a rapid diagnostic test (RDT). In SMC villages, CHWs administered SMC to children aged 3 months to 9 years once a month for 5 months. The study was conducted from 27 July to 31 December 2011. The primary outcome was malaria (fever or history of fever with a positive RDT). The prevalence of anaemia and parasitaemia was measured in a survey at the end of the transmission season. Molecular markers associated with resistance to SMC drugs were analysed in samples from incident malaria cases and from children with parasitaemia in the survey. SMC was well tolerated with no serious adverse reactions. There were 1,472 RDT-confirmed malaria cases in the control villages and 270 in the SMC villages. Among children under 5 years of age, the rate difference was 110.8/1,000/month (95% CI 64.7, 156.8; p < 0.001) and among children 5-9 years of age, 101.3/1,000/month (95% CI 66.7, 136.0; p < 0.001). The mean haemoglobin concentration at the end of the transmission season was higher in SMC than control villages, by 6.5 g/l (95% CI 2.0, 11; p = 0.007) among children under 5 years of age, and by 5.2 g/l (95% CI 0.4, 9.9; p = 0.035) among children 5-9 years of age. The prevalence of parasitaemia was 18% in children under 5 years of age and 25% in children 5-9 years of age in the control villages, and 5.7% and 5.8%, respectively, in these 2 age groups in the SMC villages, with prevalence differences of 12.5% (95% CI 6.8%, 18.2%; p < 0.001) in children under 5 years of age and 19.3% (95% CI 8.3%, 30.2%; p < 0.001) in children 5-9 years of age. The pfdhps-540E mutation associated with clinical resistance to sulfadoxine-pyrimethamine was found in 0.8% of samples from malaria cases but not in the final survey. Twelve children died in the control group and 14 in the SMC group, a rate difference of 0.096/1,000 child-months (95% CI 0.99, 1.18; p = 0.895). Limitations of this study include that we were not able to obtain blood smears for microscopy for all suspected malaria cases, such that we had to rely on RDTs for confirmation, which may have included false positives., Conclusions: In this study SMC for children under 10 years of age given over 5 months was feasible, well tolerated, and effective in preventing malaria episodes, and reduced the prevalence of parasitaemia and anaemia. SMC with CCM achieved high coverage and ensured children with malaria were promptly treated with artemether-lumefantrine., Trial Registration: www.clinicaltrials.gov NCT01449045., Competing Interests: The authors have declared that no competing interests exist.

Background: Acute Respiratory Infections (ARI) are common causes of febrile illnesses in many settings in Senegal. These infections are usually managed presumptively due to lack of appropriate diagnostic tools. This situation, can lead to poor management of febrile illness or antibiotic misuse. In addition, there are limited data on the spectrum of pathogens commonly responsible for these ARI. This study was conducted to explore the pathogens community among patients with acute respiratory infection in a rural area in Senegal., Methods: A cross sectional study was conducted from August to December 2015. Children and adult patients attending Keur Socé health post for signs suggestive of acute respiratory infection were enrolled after providing inform consent. Eligible participants were recruited using a consecutive sampling method. Paired nose and throat swabs were collected for pathogen detection. Samples were processed using a multiplex PCR designed to identify 21 pathogens including both virus and bacteria., Results: Two hundred and fifty patients participated in the study. Samples positivity rate was evaluated at 95.2% (238/250). Streptococcus pneumoniae was the predominant pathogen (74%) and was present in all months and all age-groups, followed by Staphylococcus aureus (28,8%) and rhinovirus (28,4%). Respiratory syncytial virus (RSV) was detected only among children under 5 years old in August and September while coronavirus was present in all age groups, during the months of October and December., Conclusion: This pilot study revealed a diversity of pathogens over the time and across all age groups, highlighting the need for further exploration. A pathogen community approach including both virus and bacteria at a larger scale becomes crucial for a better understanding of transmission dynamics at population level in order to help shape ARI control strategies.

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.

Background: The World Health Organization (WHO) recommends the use of insecticide-treated nets (ITNs) and intermittent preventive treatment in pregnancy (IPTp) as a cost-effective intervention for the prevention of malaria during pregnancy in endemic areas. This study was conducted to investigate: (1) the extent of use of both IPTp and ITNs, and (2) conduct multinomial regression to identify factors affecting the optimal usage of IPTp and ITNs among women with a recent pregnancy in Senegal., Methods: Data was drawn from the 2013-2014 Demographic and Health Survey. A total of 4616 women aged 15-49 years old, who had a recent pregnancy were analyzed. Multinomial logistic regression model was used to assess factors associated with optimal uptake of malaria preventive strategies (both IPTp and ITN use)., Results: Amongst women who had a recent pregnancy, less than half of them used ITNs (46.84%) however, 80.35% reported taking IPTp during their last pregnancy. Overall, 37.51% reported using the optimal malaria preventive strategies. Women aged 35-49 years and living in the richer or middle wealth quintile were more likely to use optimal prevention methods. Pregnant women living in Diourbel, Saint-Louis, Thies, Louga, Fatick and Matam were more likely to use both IPTp-SP and ITNs compared to those living in Dakar. Additionally, women who initiated antenatal care in at least at 6 weeks of pregnancy or who attended four antenatal visits or more were more likely to use optimal malaria preventive methods during pregnancy., Conclusions: This study has shown important factors that influence the uptake of malaria prevention methods during pregnancy in Senegal. These findings highlight the need for targeted preventive strategies when designing and implementing policies aimed at improving the uptake of these measures during pregnancy in Senegal.

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., (© The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

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., Competing Interests: The authors have declared that no competing interests exist.

Background: It is recommended that children aged 3 months to five years of age living in areas of seasonal transmission in the sub-Sahel should receive Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) during the malaria transmission season. The purpose of this study was to evaluate the safety of SMC with SPAQ in children when delivered by community health workers in three districts in Senegal where SMC was introduced over three years, in children from 3 months of age to five years of age in the first year, then in children up to 10 years of age., Methods: A surveillance system was established to record all deaths and all malaria cases diagnosed at health facilities and a pharmacovigilance system was established to detect adverse drug reactions. Health posts were randomized to introduce SMC in a stepped wedge design. SMC with SPAQ was administered once per month from September to November, by nine health-posts in 2008, by 27 in 2009 and by 45 in 2010., Results: After three years, 780,000 documented courses of SMC had been administered. High coverage was achieved. No serious adverse events attributable to the intervention were detected, despite a high level of surveillance., Conclusions: SMC is being implemented in countries of the sub-Sahel for children under 5 years of age, but in some areas the age distribution of cases of malaria may justify extending this age limit, as has been done in Senegal. Our results show that SMC is well tolerated in children under five and in older children. However, pharmacovigilance should be maintained where SMC is implemented and provision for strengthening national pharmacovigilance systems should be included in plans for SMC implementation., Trial Registration: ClinicalTrials.gov NCT 00712374., Competing Interests: The authors have declared that no competing interests exist.

Malaria incidence has markedly declined in the Mbour, Fatick, Niakhar and Bambey districts (central and western Senegal) thanks to a scaling up of effective control measures namely LLINs (Long Lasting Insecticide Treated Net), ACTs (Artesunate Combination Therapy) and promoting care seeking. However malaria cases are now maintained by foci of transmission called hotspots. We evaluate the role of anopheles breeding sites in the identification of malaria hotspots in the health districts of Mbour, Fatick, Niakhar and Bambey. Surveys of breeding sites were made in 6 hotspot villages and 4 non-hotspot villages. A sample was taken in each water point with mosquito larvae by dipping method and the collected specimens were identified to the genus level. Additional parameters as name of the village and breeding sites, type of collection, original water turbidity, presence of vegetation, proximity to dwellings, geographic coordinates, sizes were also collected. Sixty-two water collections were surveyed and monitored between 2013 and 2014. Temporary natural breeding sites were predominant regardless of the epidemiological status of the village. Among the 31 breeding sites located within 500 meters of dwellings in hotspots villages, 70% carried Anopheles larvae during the rainy season while 43% of the 21 breeding sites located at similar distances in non-hotspot villages carried Anopheles larvae during the same period (P = 0.042). At the end of the rainy season, the trend is the same with 27% of positive breeding sites in hotspots and 14% in non-hotspots villages. The breeding sites encountered in hotspots villages are mostly small to medium size and are more productive by Anopheles larvae than those found in non-hotspot area. This study showed that the high frequency of smallest and productive breeding sites around and inside the villages can create conditions of residual transmission.

Background: In Senegal, considerable efforts have been made to reduce malaria morbidity and mortality during the last decade. This resulted in a marked decrease of malaria cases. With the decline of malaria cases, transmission has become sparse in most Senegalese health districts. This study investigated malaria hotspots in Keur Soce sites by using geographically-weighted regression. Because of the occurrence of hotspots, spatial modelling of malaria cases could have a considerable effect in disease surveillance., Methods: This study explored and analysed the spatial relationships between malaria occurrence and socio-economic and environmental factors in small communities in Keur Soce, Senegal, using 6 months passive surveillance. Geographically-weighted regression was used to explore the spatial variability of relationships between malaria incidence or persistence and the selected socio-economic, and human predictors. A model comparison of between ordinary least square and geographically-weighted regression was also explored. Vector dataset (spatial) of the study area by village levels and statistical data (non-spatial) on malaria confirmed cases, socio-economic status (bed net use), population data (size of the household) and environmental factors (temperature, rain fall) were used in this exploratory analysis. ArcMap 10.2 and Stata 11 were used to perform malaria hotspots analysis., Results: From Jun to December, a total of 408 confirmed malaria cases were notified. The explanatory variables-household size, housing materials, sleeping rooms, sheep and distance to breeding site returned significant t values of -0.25, 2.3, 4.39, 1.25 and 2.36, respectively. The OLS global model revealed that it explained about 70 % (adjusted R(2) = 0.70) of the variation in malaria occurrence with AIC = 756.23. The geographically-weighted regression of malaria hotspots resulted in coefficient intercept ranging from 1.89 to 6.22 with a median of 3.5. Large positive values are distributed mainly in the southeast of the district where hotspots are more accurate while low values are mainly found in the centre and in the north., Conclusion: Geographically-weighted regression and OLS showed important risks factors of malaria hotspots in Keur Soce. The outputs of such models can be a useful tool to understand occurrence of malaria hotspots in Senegal. An understanding of geographical variation and determination of the core areas of the disease may provide an explanation regarding possible proximal and distal contributors to malaria elimination in Senegal.

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.

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.

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: 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.

Rapid diagnosis tests (RDTs) allow for the confirmation of malaria diagnosis. In Senegal, RDTs detecting HRP2 have been adopted in 2008 for malaria diagnosis. However, the sustainability of this strategy requires adequate and regular quality control. PCR on DNA extracted in nitrocellulose band of RDTs enable quality control. A RDT (Malaria Antigen P.f®) and a thick smear were performed on patients with suspected malaria. DNA was extracted from the nitrocellulose band of RDTs to which a non-specific PCR and a specific PCR were applied. The results of the RDT were compared with those obtained from the thick smear and the PCR to measure sensitivity, specificity as well as positive and negative predictive values. For 81.6% of the 273 patients involved, the thick smear was positive. Rapid diagnosis tests were positive for 85.7% of the patients. Non-specific PCR was positive on 87.9% of RDTs. Plasmodium falciparum was found in 99.5% of patients and Plasmodium ovale appeared in only 0.4% of patients. Sensitivity of the Malaria Antigen Pf® RDT in relation to thick smear and to PCR was 98.2% and 97.1% respectively. Quality control with PCR on the nitrocellulose band performed several months after it was used confirms its adequate level of sensitivity. The collection and screening of DNA present in already used RDT is a good means of quality control for this tool. It is also a relevant alternative to the molecular approach in the context of a reduction in the transmission of malaria.

Background: There are insufficient data on the safety in early pregnancy of the artemisinins, a new class of antimalarials. Assessment of drug teratogenicity requires large sample sizes for an adequate risk-benefit assessment. There is currently limited pharmacovigilance infrastructure in malaria-endemic countries. Monitoring drug safety in early pregnancy is especially challenging, as it requires early pregnancy detection to assess any potential increased risk of miscarriage, prospective follow-up to reduce recall and survival biases, and accurate data on gestational age assessment. Record linkage approaches for pregnancy pharmacovigilance using routinely generated health records could be a pragmatic and cost-effective approach for pharmacovigilance in early pregnancy, but has not been evaluated in resource-poor settings., Objective: Our objective was to assess the feasibility of record linkage using routinely collected healthcare data as a pragmatic means of monitoring the safety in early pregnancy of artemisinin-based combination therapies (ACTs) in Senegal., Methods: Data (2004-2008) from paper-based registers from outpatient clinics, antenatal care services (ANC) and the delivery unit from the St Joseph dispensary in Mlomp, south-western Senegal, were entered into databases. Record linkage based on a probabilistic matching approach was used to identify pregnancies exposed to ACTs in the first trimester of pregnancy. Two record linkage software packages (Link-Plus and FRIL) were compared and output data were reviewed independently by two investigators., Results: Information on 685 pregnancies was extracted, 536 of which were from the geographic catchment area and eligible for record linkage; 94.6 % of them resulted in live births, 2.6 % in stillbirths and 2.8 % in miscarriages. Major congenital malformations were identified in 1.6 % of births. Seventy-three and 75 true matches between pregnancy outcome and the outpatient treatment registers were identified by two different record linkage software packages, respectively. Record linkage identified seven exposures to ACTs in the first trimester, all of which resulted in normal live-births., Conclusion: Probabilistic record linkage is a potentially cost-effective method to assess the safety of antimalarials in early pregnancy in resource-constrained settings to assess increased risk of overall birth defects, and stillbirths in settings with good existing health records and well defined target populations.

Background: The National Malaria Control Programme in Senegal, introduced since 2006, artemisinin-based combination therapy (ACT administration) for the treatment of uncomplicated malaria cases. In this framework, an anti-malarial pharmacovigilance plan was developed and implemented in all public health services. This study investigated the occurrence of Adverse Drug Events (ADEs) after ACT., Methods: The study was conducted between January 2007 and December 2009. It was based on spontaneous reports of ADEs in public health facilities. Data on patient demographic characteristics, dispensing facility, adverse signs and symptoms and causality were collected from a total of 123 patients., Results: The age range of these patients was six months to 93 years with a mean of 25.9 years. Of the reported symptoms, 46.7% were related to the abdomen and the digestive system. Symptoms related to the nervous system, skin and subcutaneous tissue, circulatory and respiratory systems and general symptoms and signs were 7%, 9.7%, 3.5% and 31.3%, respectively. Causality results linked 14.3% of symptoms to Falcimon® (Artesunate-Amodiaquine) with certainty. Effects were classified as mild and severe in 69.1% and 7.3% of cases respectively while 23.6% were serious. All patients with serious ADEs were hospitalized. One death was reported in a patient who had taken 24 pills at once., Conclusion: These results confirm the need to develop and implement pharmacovigilance systems in malaria endemic countries in order to monitor the safety of anti-malarial treatments.

Background: As more point of care diagnostics become available, the need to transport and store perishable medical commodities to remote locations increases. As with other diagnostics, malaria rapid diagnostic tests (RDTs) must be highly reliable at point of use, but exposure to adverse environmental conditions during distribution has the potential to degrade tests and accuracy. In remote locations, poor quality diagnostics and drugs may have significant negative health impact that is not readily detectable by routine monitoring. This study assessed temperature and humidity throughout supply chains used to transport and store health commodities, such as RDTs., Methods: Monitoring devices capable of recording temperature and humidity were deployed to Burkina Faso (8), Senegal (10), Ethiopia (13) and the Philippines (6) over a 13-month period. The devices travelled through government supply chains, usually alongside RDTs, to health facilities where RDTs are stored, distributed and used. The recording period spanned just over a year, in order to avoid any biases related to seasonal temperature variations., Results: In the four countries, storage and transport temperatures regularly exceeded 30.0°C; maximum humidity level recorded was above 94% for the four countries. In three of the four countries, temperatures recorded at central storage facilities exceeded pharmaceutical storage standards for over 20% of the time, in another case for a majority of the time; and sometimes exceeded storage temperatures at peripheral sites., Conclusions: Malaria RDTs were regularly exposed to temperatures above recommended limits for many commercially-available RDTs and other medical commodities such as drugs, but rarely exceeded the recommended storage limits for particular products in use in these countries. The results underline the need to select RDTs, and other commodities, according to expected field conditions, actively manage the environmental conditions in supply chains in tropical and sub-tropical climates. This would benefit from a re-visit of current global standards on stability of medical commodities based in tropical and sub-tropical climatic zones.

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

The Research Center for Human Development in Dakar (CRDH) with the technical assistance of ICF Macro and the National Malaria Control Programme (NMCP) conducted in 2008/2009 the Senegal Malaria Indicator Survey (SMIS), the first nationally representative household survey collecting parasitological data and malaria-related indicators. In this paper, we present spatially explicit parasitaemia risk estimates and number of infected children below 5 years. Geostatistical Zero-Inflated Binomial models (ZIB) were developed to take into account the large number of zero-prevalence survey locations (70%) in the data. Bayesian variable selection methods were incorporated within a geostatistical framework in order to choose the best set of environmental and climatic covariates associated with the parasitaemia risk. Model validation confirmed that the ZIB model had a better predictive ability than the standard Binomial analogue. Markov chain Monte Carlo (MCMC) methods were used for inference. Several insecticide treated nets (ITN) coverage indicators were calculated to assess the effectiveness of interventions. After adjusting for climatic and socio-economic factors, the presence of at least one ITN per every two household members and living in urban areas reduced the odds of parasitaemia by 86% and 81% respectively. Posterior estimates of the ORs related to the wealth index show a decreasing trend with the quintiles. Infection odds appear to be increasing with age. The population-adjusted prevalence ranges from 0.12% in Thillé-Boubacar to 13.1% in Dabo. Tambacounda has the highest population-adjusted predicted prevalence (8.08%) whereas the region with the highest estimated number of infected children under the age of 5 years is Kolda (13940). The contemporary map and estimates of malaria burden identify the priority areas for future control interventions and provide baseline information for monitoring and evaluation. Zero-Inflated formulations are more appropriate in modeling sparse geostatistical survey data, expected to arise more frequently as malaria research is focused on elimination.

Background: While WHO recently recommended universal parasitological confirmation of suspected malaria prior to treatment, debate has continued as to whether wide-scale use of rapid diagnostic tests (RDTs) can achieve this goal. Adherence of health service personnel to RDT results has been poor in some settings, with little impact on anti-malarial drug consumption. The Senegal national malaria control programme introduced universal parasite-based diagnosis using malaria RDTs from late 2007 in all public health facilities. This paper assesses the impact of this programme on anti-malarial drug consumption and disease reporting., Methods and Findings: Nationally-collated programme data from 2007 to 2009 including malaria diagnostic outcomes, prescription of artemisinin-based combination therapy (ACT) and consumption of RDTs in public health facilities, were reviewed and compared. Against a marked seasonal variation in all-cause out-patient visits, non-malarial fever and confirmed malaria, parasite-based diagnosis increased nationally from 3.9% of reported malaria-like febrile illness to 86.0% over a 3 year period. The prescription of ACT dropped throughout this period from 72.9% of malaria-like febrile illness to 31.5%, reaching close equivalence to confirmed malaria (29.9% of 584,873 suspect fever cases). An estimated 516,576 courses of inappropriate ACT prescription were averted., Conclusions: The data indicate high adherence of anti-malarial prescribing practice to RDT results after an initial run-in period. The large reduction in ACT consumption enabled by the move from symptom-based to parasite-based diagnosis demonstrates that effective roll-out and use of malaria RDTs is achievable on a national scale through well planned and structured implementation. While more detailed information on management of parasite-negative cases is required at point of care level to assess overall cost-benefits to the health sector, considerable cost-savings were achieved in ACT procurement. Programmes need to be allowed flexibility in management of these funds to address increases in other programmatic costs that may accrue from improved diagnosis of febrile disease.

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.

Paediatric formulations of artemisinin combination therapies (ACTs) have recently been developed for the treatment of children with falciparum malaria. Compared with conventional tablet formulations, the new non-tablet preparations have shown equivalent efficacy, safety, and tolerability in individual trials. We aimed to investigate whether objective evidence supports the development and use of paediatric ACTs. A systematic review identified seven studies involving 2515 children that were eligible for meta-analysis. Similar efficacy and safety were seen in pooled analyses of paediatric and conventional formulations. 23 (2.0%) of 1154 patients in the paediatric formulation groups and 19 (1.7%) of 1137 in the tablet formulation groups were not cured (RR 1.27, 95% CI 0.66-2.44). Despite similar overall tolerability, the tolerability of drug administration was improved for paediatric formulations as shown by significantly fewer patients with drug-induced vomiting (93 of 1018 and 114 of 837 patients; risk ratio [RR] 0.78, 95% CI 0.61-0.99), and drug-related gastrointestinal disorders (8 of 545 and 15 of 358 patients; RR 0.36, 95% CI 0.15-0.85). These data provide, for the first time, evidence for improved management of children by use of paediatric formulations, and support the further development and use of paediatric ACTs., (Copyright 2010 Elsevier Ltd. All rights reserved.)

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/microL, 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.

Co-infection between intestinal parasites and Plasmodium falciparum is very frequent in inter tropical zone. Our study carried out in the North of Senegal (zone of high prevalence of schistosomiasis) aimed at measuring the influence of the carriage of intestinal parasites on the intensity of malaria infection. The Plasmodium falciparum densities were significantly higher during Plasmodium falciparum/Schistosoma mansoni and Plasmodium falciparum/Ascaris lumbricoides co-infection in children under 14 years old. Other intestinal parasites did not seem to have negative influence on the intensity of Plasmodium falciparum infection.

Background: It is important to establish whether or not the presence of malaria parasites in peripheral blood of asymptomatic individuals is a predictor of future clinical mild malaria attacks (MMA). The aim of this study was to determine how an asymptomatic positive thick blood smear could be related to the occurrence of a MMA during the nine following days., Methods: The study was conducted in a cohort of 569 Senegalese children, who were investigated for Plasmodium falciparum asymptomatic carriage at two different times of the transmission season, the beginning (September) and the end (November). The occurrence of MMA was investigated in asymptomatic carriers and non-carriers, every three days for nine consecutive days. Survival analysis was performed and risk estimates were calculated by Cox proportional hazards model., Results: At the beginning of the transmission season, 27.8% (147/529) of the children were asymptomatic carriers (ACs) and 5.4% (8/147) of MMA occurred among these, versus 1% (4/382) among non-carriers (RR = 5.32; IC = [1.56-18.15], p = 0.008). At the end of the transmission season, the frequency of asymptomatic carriers was similar to that observed at the beginning of the season (31.9%, p = 0.15), but no MMA was detected during this period., Conclusion: A significant association between P. falciparum asymptomatic carriage and the occurrence of MMA at the beginning of the transmission season was demonstrated, with a five-fold increase in the risk of developing a MMA in ACs. In the context of a possible distribution of IPTc in the future, drug strategies may have dramatic consequences due to the existence of ACs (both long term and short term), as they seem to play an important role in the individual protection to malaria, in the most exposed age groups.

Unlabelled: In the Sahel, most malaria deaths occur among children 1-4 years old during a short transmission season. A trial of seasonal intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) and a single dose of artesunate (AS) showed an 86% reduction in the incidence of malaria in Senegal but this may not be the optimum regimen. We compared this regimen with three alternatives., Methods: 2102 children aged 6-59 months received either one dose of SP plus one dose of AS (SP+1AS) (the previous regimen), one dose of SP plus 3 daily doses of AS (SP+3AS), one dose of SP plus three daily doses of amodiaquine (AQ) (SP+3AQ) or 3 daily doses of AQ and AS (3AQ+3AS). Treatments were given once a month on three occasions during the malaria transmission season. The primary end point was incidence of clinical malaria. Secondary end-points were incidence of adverse events, mean haemoglobin concentration and prevalence of parasites carrying markers of resistance to SP., Findings: The incidence of malaria, and the prevalence of parasitaemia at the end of the transmission season, were lowest in the group that received SP+3AQ: 10% of children in the group that received SP+1AS had malaria, compared to 9% in the SP+3AS group (hazard ratio HR 0.90, 95%CI 0.60, 1.36); 11% in the 3AQ+3AS group, HR 1.1 (0.76-1.7); and 5% in the SP+3AQ group, HR 0.50 (0.30-0.81). Mutations associated with resistance to SP were present in almost all parasites detected at the end of the transmission season, but the prevalence of Plasmodium falciparum was very low in the SP+3AQ group., Conclusions: Monthly treatment with SP+3AQ is a highly effective regimen for seasonal IPT. Choice of this regimen would minimise the spread of drug resistance and allow artemisinins to be reserved for the treatment of acute clinical malaria.

Background: Quinine injection is the reference treatment for malaria when oral administration is impossible. Quinine can also be administered by the intra-rectal route and, over the last ten years, a series of studies have been conducted in children to determine the ideal dose and dilution in the African situation. The aim of the present study was to evaluate the feasibility and usefulness of a kit for an immediate administration of quinine alkaloids (Quinimax) by community health workers, prior to transfer of the child to a more sophisticated health care establishment., Methods: A prospective, open, descriptive community intervention study conducted in northern Senegal at six village Health Units in children fewer than ten years of age with non-per-os malaria. Controls were given the routine care prior to transfer to a Health Center, and cases were in addition administered Quinimax (20 mg/ml) via the intra-rectal route before transfer. Patients were followed through complete cure and parasitological tests were carried out on Days 0, 3 and 7., Results: 134 patients (79 cases/55 controls) were recruited between November 2003 and May 2004 or October and November 2004. The two groups were comparable at inclusion. In the case group, oral drugs could be administered after a mean of 16.8 hours versus 33.6 hours in the control group. Time-to cure was shorter in cases than in controls. Complete parasite clearance was obtained in all patients by Day 7. The kit was well accepted by all concerned and more than 80% of community health workers judged the kit easy to use., Conclusion: The emergency paediatric kit is a useful tool in the management of malaria in children who cannot be treated orally. It is feasible and easy to use for health workers in community-based Health Units where, according to the WHO, nearly 80% of malarial morbidity and mortality occurs.

This study of malaria biodiversity in Senegal used an entomological approach that combined parasite surveys and clinical investigations in the mangrove area of the Saloum delta from 1996 to 1998. The parasitologic studies took place in two of the six villages in the coastal area of Palmarin (Djifère and Diakhanor) during three distinct periods: at the end of the dry season, in the middle of the rainy season, and at the end of the rainy season. The clinical investigations at the Palmarin health station took place from July 1996 through February 1998. A malaria attack was defined as the presence of malaria symptoms (including fever, headaches, sweating, and shivering) associated with plasmodic parasitemia > 3,000 trophozoites/microL of blood. All the positive thick smears were infected with Plasmodium falciparum, one also with P. falciparum, and none with P. ovale. The average plasmodic index (5.6%) classifies the delta of Saloum as a hypoendemic area. The average parasite load was estimated at 2,239 trophozoites (95% CI: 1,660-3,020) of P. falciparum per microliter of blood, and 86.9% of patients with symptoms of a malaria attack were febrile. Malaria attacks accounted for 1.9% of the total consultations, 12.2% of the presumed malaria cases, and 14.0% of the febrile subjects. The finding that malaria attacks affected all age groups confirms the weakness of anti-malaria immunity among the population of the Saloum delta. Malaria cases were more frequent at the end of the rainy season and the beginning of the dry season, periods when parasite loads were highest. In this area, which is increasingly attractive to tourists and has a quite superficial fresh water table, man-made environmental changes favor mosquito breeding sites that promote the development of An. arabiensis and An. gambiae spp, both known to be major malaria vectors. In view of the population's weak anti-malaria immunity, this situation may increase malaria transmission and could be followed by epidemics. It is therefore important to set up a functional system of epidemiological monitoring to detect any malaria outbreaks.

A study of malaria morbidity was carried out from November 1994 to October 1995, in a Ferlo village (Barkedji) characterized by a long persistence of the temporary ponds. The objective was to evaluate the repercussions of the strong and long anopheles transmission in humans. A clinical follow-up of a group of residents was conducted at home every 10 days by an investigator trained for taking axillary temperature and making thick smears, when suspecting malaria. Were included in the group, 123 voluntary subjects among whom 50% were children under 10 years old. Any feverish subject (T degree >37 degrees 5) or subject presenting other malaria symptoms (headaches, hot body shivers, sweats, aches...) was regarded as having a malaria attack as well as a parasitemia >2500 P/mm3 in children aged of 0 to 14 years old and 1000 P/mm3 in the oldest. During the study subjects with at least one feverish access, plasmodium infection and malaria attack were 58%, 33% and 22%, respectively. On 172 hyperthermias observed, 49% were accompanied by a circulating parasitemia and 30% corresponded to malaria attack. The feverish subjects (74% vs. 42%), the subjects with parasitemia (51% vs. 16%) and the cases of malaria (34% vs. 10%) were more frequently encountered in children under10 than in the oldest. The cases of malaria attacks were more frequent from November to January (70%). The strong intensity of malaria transmission in Barkedji and the persistence of its temporary ponds until January were sufficient to influence the level of malaria morbidity and consequently the development of an anti-malaria immunity by the indigenous population.

From June 1995 to January 1998, entomological studies carried out in five villages located in the Delta's Saloum have allowed to better understand the contribution of An. melas Theobald (1903) to malaria transmission in mangrove swamp. Among the five villages studied, three of them (Simal, Djilor and Marlothie) located along the Saloum river, are colonised by An. arabiensis; the two others (Djifere and Diakhanor) located between the sea and the river, are colonised by An. melas. During the rainy season and at the beginning of the dry season, An. melas and An. arabiensis are sympatric. The ratio of An. melas/An. arabiensis increases when we go closer the coast where An. melas becomes quite exclusive. When An. melas is predominant, endophagy, endophily and anthropophily are very marked. The parturity rates are lower in An. melas than in An. arabiensis. In the predominance area of each species, transmission is on the same level. During the period of sympatry, An. arabiensis is responsible for the transmission and when it is absent, An. melas carries on. Transmission occurs from July to March with a maximum at the beginning of the dry season. In the villages of the mangrove swamp, its prolongation until the middle of the dry season is due to An. melas.

We previously investigated malaria in the southern health district of the city of Dakar, which includes the oldest neighborhoods. In this study, we investigated malaria in the central health district, corresponding to the central area of the conurbation. The study was carried out at 12 sites, from March 1996 to February 1997. The sites were selected such that the entire district was covered and included 2 sites in the shanty town and three in an old village that has been absorbed into the city. We carried out prospective monthly entomological analyses with a view to identifying the vectors and the mode of transmission of malaria. We also carried out clinical and parasitological follow up to determine the incidence of parasitemia and of bouts of malaria. Insects were collected overnight from humans and the insects remaining the next morning in 10 bedrooms in the health district were collected. For clinical and parasitological follow up, families were visited at home once per week and their clinical state was assessed. Blood smears were taken to facilitate the detection of bouts of malaria. Body temperature was measured and we checked for the presence of organisms in the blood systematically during the last weekly visit of each month. For a total of 308 collections at night from human volunteers and 1,395 bedroom collections of residual fauna, we obtained 12,879 Culicidae females, 199 (1.5%) of which were anopheles mosquitoes, with Culex quinquefasciatus accounting for 98% of the remaining mosquitoes. As in the southern district, A. arabiensis was the only species of the A. gambiae complex collected. Anopheles mosquitoes accounted for only 0.3 bites per man per night and 0.07 females per room. They were therefore poorly represented in this district and were not detected at all at five sites. They were found in large numbers only during the rainy season, especially in September, when they accounted for 2.25 bites per man per night and 0.3 females per room at 3 sites in an undeveloped zone in which 81.4% of all the anopheles mosquitoes were collected. The parturition frequency of the biting females was 32.6% and that of the females collected in houses was 50.0%. None of the A. arabiensis females dissected (98.5% of those collected) carried Plasmodium sporozoites. The clinical and parasitological follow up concerned 2,583 individuals, aged from 1 month to 80 years, from 285 families resident in Dakar who volunteered for the study; 41.9% of these individuals were less than 15 years old and 92.2% had been living in Dakar for more than 2 years. Thick and thin blood smears taken monthly showed the frequency of the parasite to be 1.0% and that of gametocytes to be 0.1%. P. falciparum was the only parasite detected in the subjects. Plasmodium infections were observed in all age groups, with a frequency of 0.4% (adults over the age of 20 years) to 1.6% (children under two years of age). Parasitized subjects were detected in every month of the study, with a frequency of 0.4% (in January) to 1.9% (in December). The largest number of cases detected in a three-month period (38.8% of all cases) was that for October to December, the three-month period immediately after the rainy season (July to September). Parasite frequency, which was no higher than 1. 2% at 10 sites, was clearly higher at two sites in the shanty town (3.8 and 6.8%), mostly inhabited by immigrants from rural areas. At the end of the study year, satisfactory weekly follow up was considered to have been achieved for 1,067 of the participants. The annual incidence of parasitemia in this cohort was 5.1% and that of malaria was 2.4%. Incidence did not vary significantly with age and was between 1.8% and 7.6% for parasitemia and between 0.8% and 3.5% for malaria. However, significant differences in incidence were observed between areas. Incidence was higher at the two sites in the shanty town, with rates of 12.1% and 36.5% for parasitemia and 6.1% and 15.9% for malaria. (ABSTRACT TR

Blood-engorged females of An. gambiae s.l., An. funestus, An. pharoensis and An. rufipes caught resting indoors were tested (precipitin or enzyme-linked immunosorbent assay) to determine the source of bloodmeal. The species of the An. gambiae complex fed mainly on human hosts in all prospected areas, except in those of the mid Senegal river valley where an important zoophily was observed within and near the irrigation zone. Among 4,597 blood-engorged females of An. gambiae s.l., 29% fed on cattle with 7.5% of mixed boodmeals, mainly human-bovine or human-equine. The presence of cattle, culicid population densities and individual mosquito safety devices were the most determinant factors of animal deviation. Blood of most domestic animals was found in the stomach of collected females, but according to areas, bovines and equines were the main hosts for zoophilic females of An. gambiae s.l. Females of An. funestus collected in the middle-west were more anthropophilic than those collected in south-eastern areas. An. pharoensis was most prevalent in the Senegal river delta where it was found to be very anthropophilic. An. rufipes was strongly endophilic but exclusively zoophilic in all prospected areas.

The Sahel region has been suffering from severe drought for the last thirty years, with large deficits and a high degree of variability in the amount of annual rainfall. Agricultural production in the Sahelian zone of the Senegal River valley depends on the flooding of the river. The management of this flooding affects malaria transmission. The area is prone to malaria epidemics because the immunity level of the population is low. We studied epidemiological, meteorological and river level data to identify epidemic risk factors. We propose an epidemiological and managerial system for the early detection of risks and early intervention. This system is based mainly on the water level of the Senegal River and the early detection of unusual increases in the number of cases.

In order to assess the parasitic risks related to Ferlo's valley water launching, a study has been carried out from september 15 to october 10, 1996 in 12 villages. Four villages surrounding the Guiers lake, four lower within lower Ferlo already water launched 7 years ago, and four villages within upper Ferlo not water launched. Malaria strikes at hypoendemic level in the villages surrounding the Guiers lake (p.i = 6.2%) and at mesoendemic level in the area stretching along lower (P.I = 37.6%) and upper Ferlo (P.I = 34.3%) The prevalence rate of urinary bilharziosis is 0.002% in the first area, 1.3% in the second one and 14.5% in the third area. In these areas, intestinal parasitosis were prevailing respectively at rates of 38.2%, 36.4% and 22.2%. Although, there is no reason to fear immediately a worsening of the epidemiological situation due to Ferlo's valley revitalisation project, nevertheless, appropriate steps should be taken right now aiming at tacking the extension of conditions related to hydric medium.

A survey of endemic malaria in Dakar was carried out in the southern sanitary district covering the city centre and neighbouring areas. The survey was scheduled from June 1994 to May 1995 in 12 sites distant from each other by 1000 to 1500 meters. Clinical and parasitological data were collected during weekly medical follow-ups at the patients' home with the systematic research of Plasmodium once a month. The study included 2,337 persons aged between 1 month and 88 years and belonging to 284 volunteer resident families. Through monthly parasitological examinations, a parasite rate (P.R.) of 0.3% and a gametocyte rate (G.R.) of 0.005% were recorded. Only Plasmodium falciparum was observed. The P.R. varied according to age: from 0.1% in the children under 2 years to 0.7% in the young adults (15-20 years) who appeared significantly more affected than the other age groups, including that of children from 2 to 9 years, of whom only 0.3% were infected by the parasite. The P.R. varied also according to the site surveyed: from 0% in the city centre to 1.3% at the periphery of the sanitary district and according to the time of year, reaching its height of 0.8%, between October and December, that is just after the rainy season. At the end of the year of survey, 929 among those surveyed were considered to have been satisfactorily followed. Their annual incidence rate was 2.4% for the parasitemia and of 1.5% for the malaria attacks. None of the participants aged under 2 years had the parasite. Among the others, the annual incidence rate varied according to the age--although not significantly--passing from 1.1% to 5.3% for parasitemia and from 0.4% to 3.0% for malaria attacks. Theses rates did not differ significantly according to site; the cases registered varied between 1% and 8% for parasitemia and 1% and 5.8% for malaria attacks. Only 10.6% of febrile subjects suffered from malaria attacks, but this rate seemed to go up between October to December, rising to 26.6% which corresponds to 1 case of malaria attacks for 4 cases of hyperthermia in that period. Weak density of Anopheline population and satisfactory medical surveillance explain the recorded results.

To determine risk factors for fatal malaria in Senegalese children, a 3-year case-control study was carried out between October 1992 and November 1995 at the Albert Royer Hospital in Dakar. The case group included 52 children who died from documented malaria in the hospital. The matched control group consisted of children who responded favorably to hospital treatment. Exposure to risk was measured with regard to age, nutritional status, educational level of parents, self-medication prior to hospitalization, socioeconomic level, degree of fever, and blood parasite levels. Cases and controls were compared using statistical tests for matched groups. Age lower than 5 years, poor educational level of parents, delay of treatment more than 24 hours, nutritional status, and blood parasite levels greater than 5% were associated with a significantly higher risk of fatal outcome. Conversely, low socio-economic level, recent self-medication, and fever over 41 degrees C were not associated with higher fatality. These findings emphasize the need for more information campaigns to encourage people to seek institutionalized care when fever appears. Our results also suggest that prophylactic treatment may be advisable in children under 5 years of age and in some high risk groups.

The efficacy of permethrin-treated bednets was evaluated in Wassadou, a hyperendemic village located in the Sudanese grasslands of southeast Senegal. Pretreatment data were collected between 1992 and 1993. Bednets were distributed to the whole population in June 1995 and impact of their use on vector populations and malaria transmission was evaluated until November 1995. This period corresponds to the rainy season during which malaria transmission is highest. Data were compared with a control village in which bednets were not distributed. Findings showed that use of bednets led to a sharp decrease in the density of the vector population and malaria transmission. The number of bites by Anopheles gambiae s.1. decreased 69%. The density of blood-laden and pregnant females inside dwellings decreased 91% and 96% respectively. The sporozoite index of females captured on the skin decreased 76% and the daily rate of entomological inoculation decreased 88%. This impact was not great enough to eliminate the risk of infection. Prolonged study over a period of 4 to 5 years is needed to evaluate the impact of long-term use of insecticide-treated bednets on vector population and malaria transmission.

The authors carried out an epidemiological survey from october 12 to december 4, 1995, at Medina's mother and Child care centre (MCC) in Dakar in order to assess chemoprophylaxis among pregnant women in Dakar. The midwife/pregnant women ratio is 0.08 The mentioned diagnosis criteria were relevant regards to the references established for most of the answers because since the latter base malaria diagnosis on the following signs: fever, chills, headaches and vomiting. 64.6% of them assume compliance to antimalarial chemoporphylaxis. Education level seems to be the main determining factor in this trend. Although chloroquine is the most widely used drug, nevertheless 11.9% of pregnant women assuming compliance use it at inappropriate posology. Besides, pyrimethamine is used by 12.3% of them. 34% of pregnant women do show chloroquine in urine. The plasmodial index is 1.4%. Only 8.1% of these women are supplied by health centres where shortages are noted.

Evaluating knowledge about the diagnosis and treatment of malaria is a prerequisite for both understanding the development of chemoresistance and improving ongoing programs of chemotherapy and chemoprophylaxis. To gain such knowledge we distributed a questionnaire to 900 household heads in twelve villages in the M'Backe district of Senegal. Awareness of the main symptoms of malaria was satisfactory in comparison with previous references. Public health care facilities such as dispensaries were cited as the first resort for treatment by 72.6% of respondents. Chloroquine was mentioned as the first line antimalarial by 23% of respondents who practiced self-medication. Improper dosages were stated by 60% of the respondents. A total of 52.3% of respondents practiced chemoprophylaxis mainly using chloroquine. In 65.8% of cases antimalarial drugs were obtained from public health care units but drugs were purchased on the market in 15.7% of cases. These findings indicate the threefold Bamako initiative should be reinforced and that a campaign should be undertaken to educate people living in rural areas about malaria.

In Senegal, identifying the determining factors of the informal health care demand for malaria on the one hand and the supply's inventory in that condition on the other hand, are prerequisites to the definition of any realistic pharmaceutical policy. Wanted to make these parameters available in the city of Touba which shows religious and administrative particularities as compared to the rest of Senegal, by conducting a study on malaria morbidity and by submitting to people and informal health care providers two different questionnaires. Besides a malaria morbidity rate of 7.4%, the resort to informal health care was linked to economic reasons for 64% of householders resorting to this type of health care. Sociocultural determining factors were also identified. Among health care providers whom community's request is important, we observed the relevance of the malaria regular diagnosis as compared to established references. However we did not observed it as far as treatment and chemoprophylaxis are concerned. The supply is done along underground lines. The training of these informal health care providers and their integration in the general health care system should be considered.

From September 1992 to October 1993 a longitudinal entomological study was carried out in two villages located in different ecological conditions of Senegal, a sahelian area and a sudan-type savanna. Mosquitoes were sampled by night-bites catches and by daytime pyrethrum spray collections. In both villages Anopheles gambiae s.l. is the main vector with An. gambiae in the savanna area of Wassadou and An. arabiensis in the sahelian area of Thiaye. Malaria transmission is mainly seasonal with a man biting rate (ma) and an entomological inoculation rate (h) higher in Wassadou than in Thiaye. In this last one (sahelian area), a high variation of An. gambiae s.l. density was observed, females disappear in the dry season. In the rainy season the main biting rate increases but no infected bite was recorded. In Wassadou (sudan-type savanna), a great difference in An. gambiae s.l. specific composition was observed with An. gambiae predominant in the rainy season and An. arabiensis generally more abundant in the dry season. The biting and inoculation rates were minimum during the dry season (ma = 4 bites/man/night; h = 0.07 infected bites/man/night-, they increase during the rainy season (ma: 52 bites/man/night; h = 1.6 infected bites/man/night). An inhabitant of this village gets annually some 63, bites and 220 infected bites of An. gambiae s.l., mainly during the six months of the rainy season and the early dry season.

The practices of health care workers and the population with regard to diagnosis of malaria and use of antimalarial drugs were studied in the city of Dakar from September 1991 to March 1992. Study included 847 heads of family, 191 treatment prescribers including 77 physicians, 53 nurses and 61 midwives, and 60 pharmacists. Three separate questionnaires were used: one for the population, one for physicians and paramedical staff, and one for pharmacists. The data collected showed that the 4 main symptoms used by both health care workers and the general population for diagnosis of malaria were fever, chills, vomiting, and headache. Treatment was administered upon suspicion of infection by 72% of treatment prescribers. Chloroquine was the drug most widely used by prescribers and for self-treatment of malaria. Prophylactic drug treatment was practised by all groups studied except treatment prescribers but was unappropriate for the target groups. Chloroquine is the drug most widely used to protect against the disease. Pharmacists have adequate supplies but distribution is poor. Despite promising results in the fight against malaria, further effort is needed to train health care workers and provide information to the population.