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Background SMC was adopted in Nigeria in 2014 and by 2021 was being implemented in 18 states, over four months between June and October by 143000 community drug distributors (CDDs) to a target population of 23million children. Further expansion of SMC is planned, extending to 21 states with four or five monthly cycles. In view of this massive scale-up, the National Malaria Elimination Programme undertook qualitative research in five states shortly after the 2021 campaign to understand community attitudes to SMC so that these perspectives inform future planning of SMC delivery in Nigeria. Methods In 20 wards representing urban and rural areas with low and high SMC coverage in five states, focus group discussions were held with caregivers, and in-depth interviews conducted with community leaders and community drug distributors. Interviews were also held with local government area and State malaria focal persons and at national level with the NMEP coordinator, and representatives of partners working on SMC in Nigeria. Interviews were recorded and transcribed, those in local languages translated into English, and transcripts analysed using NVivo software. Results In total, 84 focus groups and 106 interviews were completed. Malaria was seen as a major health concern, SMC was widely accepted as a key preventive measure, and community drug distributors (CDDs) were generally trusted. Caregivers preferred SMC delivered door-to-door to the fixed-point approach, because it allowed them to continue daily tasks, and allowed time for the CDD to answer questions. Barriers to SMC uptake included perceived side-effects of SMC drugs, a lack of understanding of the purpose of SMC, mistrust and suspicions that medicines provided free may be unsafe or ineffective, and local shortages of drugs. Conclusions Recommendations from this study were shared with all community drug distributors and others involved in SMC campaigns during cascade training in 2022, including the need to strengthen communication about the safety and effectiveness of SMC, recruiting distributors from the local community, greater involvement of state and national level pharmacovigilance coordinators, and stricter adherence to the planned medicine allocations to avoid local shortages. The findings reinforce the importance of retaining door-to-door delivery of SMC.

Nigeria adopted Seasonal Malaria Chemoprevention (SMC) for children under 5 years of age as part of national malaria control policies, in 2014. By 2021 the intervention was being implemented in 18 states, delivered over 4 months between June and October by 143,000 community drug distributors (CDDs) to a target population of 23.1million children. Further expansion of SMC is planned, extending to 21 states in 2022 with a target population of 27.1 million children, and an increased number of monthly cycles, from 4 to 5, may be needed in some states. In view of this massive scale-up of SMC, the National Malaria Elimination Programme conducted a qualitative research study shortly after the 2021 campaign to understand community attitudes to SMC, and to identify barriers to uptake and facilitating factors, in order to ensure that community perspectives inform future planning of SMC delivery in Nigeria. In each of five states (Kano, Kwara, Nasarawa, Yobe and Kebbi), Local Government Areas (LGAs) were ranked based on administrative coverage of SMC in 2021, and one LGA with high coverage and one with low coverage selected. In two wards (one urban and one rural) in each LGA, focus group discussions (FGDs) were held with caregivers, and in-depth interviews (IDIs) were conducted with community leaders and with community drug distributors. State-level and LGA malaria focal persons were also interviewed. At national level, key-informant interviews (KIIs) were held with the NMEP coordinator, and representatives of partners working on SMC in Nigeria. Interviews were recorded and transcribed, and those in local languages translated into English, and the transcripts were analysed using NVivo software. A total of 190 FGDs, KIIs and IDIs were undertaken. In all study areas malaria was seen as a major health concern and SMC was widely accepted as a key preventive measure, and community drug distributors (CDDs) were generally trusted. Caregivers preferred SMC delivered door-to-door to the fixed-point approach, because in addition to allowing them to continue daily tasks, door-to-door delivery allowed more time for the CDD to explain how to administer the treatments and advise about adverse reactions and to answer questions. Barriers identified included perceived side effects of SMC drugs, a lack of understanding of the purpose of SMC, mistrust and suspicions that medicines provided free may be unsafe or ineffective. Key informants and caregivers reported SMC distributions limited by drug shortages, supplies running out before all children in the community had been treated. Key findings from this study were shared with delivery teams during national and state level training in 2022 and through cascade training to all community drug distributors and others involved in SMC campaigns. Other steps to act on the findings will include updating the training curriculum to show SMC teams how to strengthen communication to caregivers on the importance, safety and effectiveness of SMC, during campaigns; more involvement of state and national level pharmacovigilance coordinators during implementation to improve completion and submission of individual case safety reports and investigation of suspected adverse drug reactions. To avoid local shortages of SMC drugs, NMEP will ensure stricter adherence to the planned medicine allocations for each facility based on microplanning estimates. Study findings were shared with donors and implementing partners, to reinforce the importance of retaining primarily door-to-door delivery of SMC in Nigeria.

Seasonal malaria chemoprevention is used in 13 countries in the Sahel region of Africa to prevent malaria in children younger than 5 years. Resistance of Plasmodium falciparum to seasonal malaria chemoprevention drugs across the region is a potential threat to this intervention.Between December, 2015, and March, 2016, and between December, 2017, and March, 2018, immediately following the 2015 and 2017 malaria transmission seasons, community surveys were done among children younger than 5 years and individuals aged 10-30 years in districts implementing seasonal malaria chemoprevention with sulfadoxine-pyrimethamine and amodiaquine in Burkina Faso, Chad, Guinea, Mali, Nigeria, Niger and The Gambia. Dried blood samples were collected and tested for P falciparum DNA by PCR. Resistance-associated haplotypes of the P falciparum genes crt, mdr1, dhfr, and dhps were identified by quantitative PCR and sequencing of isolates from the collected samples, and survey-weighted prevalence and prevalence ratio between the first and second surveys were estimated for each variant.5130 (17·5%) of 29 274 samples from 2016 and 2176 (7·6%) of 28 546 samples from 2018 were positive for P falciparum on quantitative PCR. Among children younger than 5 years, parasite carriage decreased from 2844 of 14 345 samples (19·8% [95% CI 19·2-20·5]) in 2016 to 801 of 14 019 samples (5·7% [5·3-6·1]) in 2018 (prevalence ratio 0·27 [95% CI 0·24-0·31], p0·0001). Genotyping found no consistent evidence of increasing prevalence of amodiaquine resistance-associated variants of crt and mdr1 between 2016 and 2018. The dhfr haplotype IRN (consisting of 51Ile-59Arg-108Asn) was common at both survey timepoints, but the dhps haplotype ISGEAA (431Ile-436Ser-437Gly-540Glu-581Ala-613Ala), crucial for resistance to sulfadoxine-pyrimethamine, was always rare. Parasites carrying amodiaquine resistance-associated variants of both crt and mdr1 together with dhfr IRN and dhps ISGEAA occurred in 0·05% of isolates. The emerging dhps haplotype VAGKGS (431Val-436Ala-437Gly-540Lys-581Gly-613Ser) was present in four countries.In seven African countries, evidence of a significant reduction in parasite carriage among children receiving seasonal malaria chemoprevention was found 2 years after intervention scale-up. Combined resistance-associated haplotypes remained rare, and seasonal malaria chemoprevention with sulfadoxine-pyrimethamine and amodiaquine is expected to retain effectiveness. The threat of future erosion of effectiveness due to dhps variant haplotypes requires further monitoring.Unitaid.

Background Seasonal malaria chemoprevention (SMC) has shown high protective efficacy against clinical malaria and severe malaria in a series of clinical trials. We evaluated the effectiveness of SMC treatments against clinical malaria when delivered at scale through national malaria control programmes in 2015 and 2016. Methods and findings Case–control studies were carried out in Mali and The Gambia in 2015, and in Burkina Faso, Chad, Mali, Nigeria, and The Gambia in 2016. Children aged 3–59 months presenting at selected health facilities with microscopically confirmed clinical malaria were recruited as cases. Two controls per case were recruited concurrently (on or shortly after the day the case was detected) from the neighbourhood in which the case lived. The primary exposure was the time since the most recent course of SMC treatment, determined from SMC recipient cards, caregiver recall, and administrative records. Conditional logistic regression was used to estimate the odds ratio (OR) associated with receipt of SMC within the previous 28 days, and SMC 29 to 42 days ago, compared with no SMC in the past 42 days. These ORs, which are equivalent to incidence rate ratios, were used to calculate the percentage reduction in clinical malaria incidence in the corresponding time periods. Results from individual countries were pooled in a random-effects meta-analysis. In total, 2,126 cases and 4,252 controls were included in the analysis. Across the 7 studies, the mean age ranged from 1.7 to 2.4 years and from 2.1 to 2.8 years among controls and cases, respectively; 42.2%–50.9% and 38.9%–46.9% of controls and cases, respectively, were male. In all 7 individual case–control studies, a high degree of personal protection from SMC against clinical malaria was observed, ranging from 73% in Mali in 2016 to 98% in Mali in 2015. The overall OR for SMC within 28 days was 0.12 (95% CI: 0.06, 0.21; p < 0.001), indicating a protective effectiveness of 88% (95% CI: 79%, 94%). Effectiveness against clinical malaria for SMC 29–42 days ago was 61% (95% CI: 47%, 72%). Similar results were obtained when the analysis was restricted to cases with parasite density in excess of 5,000 parasites per microlitre: Protective effectiveness 90% (95% CI: 79%, 96%; P, Using case-control studies, Matthew Cairns and colleagues investigate the effectiveness of seasonal malaria chemoprevention against clinical malaria in children in Burkina Faso, Chad, Mali, Nigeria and The Gambia., Author summary Why was this study done? Seasonal malaria chemoprevention (SMC) consists of monthly administration of 2 antimalarial drugs, sulphadoxine–pyrimethamine and amodiaquine, to children 3–59 months of age during the peak months of malaria transmission. SMC provided a high level of protection against clinical malaria in clinical trials, and has been recommended by the World Health Organization since 2012 for areas of the Sahel and sub-Sahel regions of Africa with seasonal transmission. This study was done to determine whether the efficacy observed in the trials translated into effectiveness when SMC was deployed at scale. What did the researchers do and find? The researchers carried out case–control studies in Burkina Faso, Chad, Mali, Nigeria, and The Gambia to estimate the protective effectiveness of SMC treatments against clinical malaria. Cases were children with confirmed malaria at a health facility. For each case, 2 controls were chosen from the neighbourhood where the case lived. Dates of SMC treatments were determined from SMC record cards and by asking caregivers. The effectiveness of monthly SMC treatment in preventing clinical malaria was estimated by comparison of when cases and controls had most recently received SMC. In all 7 case–control studies (2 in 2015 and 5 in 2016), SMC provided a high level of protection against clinical malaria. Protection was highest in the first 4 weeks after treatment. Pooling estimates across the 7 studies, clinical malaria incidence during the first 4 weeks after SMC treatment was reduced on average by 88%. Protection from SMC was lower in the period 5–6 weeks post-administration. What do these findings mean? SMC was highly effective in preventing clinical malaria when delivered at scale through national malaria control programmes, with protection comparable to that observed during clinical trials. This case–control design can be used by national malaria control programmes at intervals to confirm that SMC remains effective.

Background: Optimizing antiretroviral therapy is an essential step to reach the 90 - 90 - 90 targets. Despite tremendous progress made for antiretroviral treatment (ART) to be accessible in countries with limited resources, health care providers continue to face challenges due to the under-optimization of ART due to therapeutic failures and poor retention. Objectives: To determine the prevalence of adverse therapeutic outcomes in a decentralized health care center and to determine associated factors. Patients and Methods: This is a cross-sectional descriptive and analytical study targeting PLHIV, aged 18 years and over, on first line antiretroviral treatment (ART), monitored onsite from February 1st to December 31st, 2018. A data collection form was completed from medical records (clinical, immuno-virological, therapeutic and evolutionary). Data were also collected from interviews with patients for additional socio-demographic information including the level of HIV knowledge. Data were captured and analyzed using EPI 2002 and R software. Proportions were compared using the chi -square and Fisher tests and logistic regression. A value of p Results: 331 patients were enrolled with HIV-1 profile in 89% of the cases. A proportion of 55% was married and 98% came from the rural area. 80% were either not or poorly educated. The median of age was 44 ± 11 years with a F/M ratio of 3.5. 30% that had not shared their HIV status, and more than half had a low knowledge of HIV transmission. At baseline, 56% were symptomatic at WHO stage 3 or 4. They had severe immunosuppression with a median CD4 count of 217 ± 187 cells/mm3; the viral load was detectable in half of the patients with a median viral load (VL) of 97,000 ± 70,569 cp/ml. The antiretroviral regimens combined 2 nucleoside reverse transcriptase inhibitor (NRTI) with 1 no nucleoside reverse transcriptase inhibitor (NNRTI) in 88% of the cases. The median duration of follow-up was estimated at 60 ± 43 months. The prevalence of adverse therapeutic outcomes was 36% (119 patients). The proportion of virological failure was 19%, lost follow up was 20% and the mortality was 4%. The adverse therapeutic outcomes were associated with the age less than 25 years (p = 0.007) and with a late diagnosis (CD4 T cells at baseline less than 200 cell/mm3, p = 0.02). Conclusion: These results suggest the need to make new therapeutic classes available for first-line treatment and to promote actions improving retention in care.

Background MOSKI KIT® is a fun tool designed to interest children for prevention and management of malaria. This study was carried out with the objective to assess the short- and long-term impacts of this tool on the knowledge, attitudes, and practices of school children, and on the transmission of the knowledge received at the household level as well. Method The study took place in elementary schools in the city centre (with relatively low endemicity) and in the Niayes area (at high risk of anopheline and malaria) in the Dakar region of Senegal. The various schools chosen for this study were divided into an intervention group and a control group. The intervention schools were also divided into two subgroups, a full package subgroup and another partial package. During this study three surveys were conducted, the first one before exposure to the MOSKI KIT®, the second one a week later and the third a year later. For the control schools only one survey was conducted and at the same time than the third for the intervention schools. Two household surveys (a week and a year after exposure) were also conducted for the intervention schools against one for the control schools. Results Before sensitization, the proportion of school children with a grade above or equal to the average was 50% for the complete package subgroup (CPS) and 53% for the partial package subgroup (PPS). A week later, these proportions were 69% and 71%, respectively for the complete and PPSs. A year later, they were 99.4% for the CPS, 98.1% for the PPS and 99.5% for the control group; The number of children who spoke to their parents about malaria was greater in intervention schools than that of control schools. They were 46.63% and 32.58%, respectively in intervention and control schools. Conclusion The MOSKI KIT, has enabled an increase of the knowledge of school children about malaria in the short term and favoured its retention in the long term. However, its impact was not felt on their attitudes and practices.

Background Current knowledge on the burden of, and interactions between malaria and helminth co-infections, as well as the impact of the dual infections on anaemia, remains inconclusive. We have conducted a systematic review with meta-analysis to update current knowledge as a first step towards developing and deploying coordinated approaches to the control and, ultimately, elimination of malaria-helminth co-infections among children living in endemic countries. Methodology/Principal findings We searched Medline, Embase, Global Health and Web of Science from each database inception until 16 March 2020, for peer-reviewed articles reporting malaria-helminth co-infections in children living in endemic countries. No language restriction was applied. Following removal of duplicates, two reviewers independently screened the studies for eligibility. We used the summary odds ratio (OR) and 95% confidence intervals (CI) as a measure of association (random-effects model). We also performed Chi-square heterogeneity test based on Cochrane’s Q and evaluated the severity of heterogeneity using I2 statistics. The included studies were examined for publication bias using a funnel plot and statistical significance was assessed using Egger’s test (bias if p, Author summary Updated evidence is needed to guide the planning and implementation of appropriate interventions for control of mixed infections involving malaria and worms affecting children living in endemic countries. We performed a systematic review and meta-analysis to update current knowledge on the magnitude of the burden of dual infections with malaria and worms in children in the developing world. We searched all published articles available in Medline, Embase, Global Health and Web of Science from the database inception until 16 March 2020, without any language restriction. We found 55 eligible studies, and 28 of these studies were included in the meta-analysis. A summary of the evidence synthesis showed that the burden of dual infections involving malaria and worm parasites is high in children and varies significantly across endemic countries. There was a lower risk of P. falciparum infection in children infected with soil transmitted helminths (STH) or S. haematobium or S.mansoni. Conversely, the odds of anaemia were higher in children who had dual infections with Plasmodium and STH parasites than in children with a Plasmodium infection alone while the odds of anaemia were almost equal in children who were co-infected with Plasmodium-Schistosoma compared to those with a Plasmodium infection alone. These findings underscore the need to further understand the epidemiology of malaria-helminth co-infections in order to support implementation of appropriate interventions for control and, ultimately, elimination of the dual infections in children living in endemic countries, especially low and middle-income countries (LMIC).

Background In endemic areas, children develop slowly and naturally anti-Plasmodium antibodies and become semi-immune. Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine + amodiaquine (SPAQ) is a new strategy to reduce malaria morbidity in West African young children. However, SMC may impact on the natural acquisition of anti-Plasmodium immunity. This paper evaluates the effect of SMC with SPAQ on antibody concentration in young children from Niger. Methods This research was conducted in areas benefitting from SMC since 2014 (Zinder district), without SMC (Dosso district), and with 1 year of SMC since 2016 (Gaya district). To assess the relationship between SMC and Plasmodium falciparum IgG antibody responses, the total antibody concentrations against two P. falciparum asexual stage vaccine candidate antigens, circumsporozoite protein (CSP) and glutamate-rich protein R2 (GLURP-R2), in children aged 3 to 59 months across the three areas were compared. Antibody concentrations are quantified using an enzyme-linked immunosorbent assay on the elution extracted from positive and negative malaria Rapid Diagnostic Test cassettes. Results The analysis concerns two hundred and twenty-nine children aged from 3 to 59 months: 71 in Zinder, 77 in Dosso, and 81 in Gaya. In Zinder (CSP = 17.5 µg/ml and GLURP-R2 = 14.3 µg/ml) median antibody concentration observed are higher than in Gaya (CSP = 7.7 µg/ml and GLURP-R2 = 6.5 µg/ml) and Dosso (CSP = 4.5 µg/ml and GLURP-R2 = 3.6 µg/ml) (p Conclusion The research reveals some evidences which show that seasonal malaria chemoprevention with SPAQ has an effect on blood stage antibody responses and pre-erythrocytic stage of P. falciparum infections in Niger. Increased antibody titres with increased SMC/SPAQ implementation. This contradicts hypothesis that SMC/SPAQ could reduce immunity to erythrocyte and liver-stage antigens. Further studies are necessary to provide better understanding of the SMC effect on malaria immunity.

Background: In endemic areas, children develop slowly and naturally develop anti-Plasmodium antibodies and become semi-immune. Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine + amodiaquine (SPAQ) is a new strategy to reduce malaria morbidity in young children in West Africa. However, SMC may impact on the natural acquisition of anti-Plasmodium immunity. We evaluated the effect of SMC with SPAQ on malaria antibody concentration in Niger.Methods: This survey was conducted in areas targeted with SMC since 2014 (Zinder district), without SMC (Dosso district), and with one year SMC 2016 (Gaya district). To assess the relationship between SMC and P. falciparum IgG antibody responses, we compared total antibody concentrations against two P. falciparum asexual stage vaccine candidate antigens, circumsporozoite protein (CSP) and glutamate-rich protein R2 (GLURP-R2), in children aged 3-59 months across the three sites. Antibody concentrations were quantified using an enzyme-linked immunosorbent assay (ELISA) on the elution extracted from positive and negative RDT cassettes.Results: A total of 229 children aged 3-59 months were included in the analysis: 71 in Zinder, 77 in Dosso, and 81 in Gaya. In Zinder (CSP=17.5µg/ml and GLURP-R2=14.3µg/ml) median antibody concentration observed were higher than in Gaya (CSP=7.7 µg/ml and GLURP-R2=6.5 µg/ml) and Dosso (CSP=4.5 µg/ml and GLURP-R2=3.6 µg/ml) (pConclusion: We have some evidence that seasonal malaria chemoprevention with SPAQ has an effect on blood stage antibody responses and pre-erythrocytic stage of Plasmodium falciparum infections in Niger. Future studies are necessary to provide better understanding of the effect of on malaria immunity.

Introduction: In Senegal, the decentralization of Health Care Centers has contributed significantly to the intensification of antiretroviral treatment. However, Care providers are still facing the treatment optimizing challenge. Objectives: To determine the prevalence of virologic failures of PLHIV monitored in a decentralized Health care center and to determine associated factors. Patients and Methods: This is a cross-sectional descriptive and analytical study of PLHIV, aged 18 years and over, on first-line treatment, monitored onsite from February 1st to December 31st, 2018. A data collection form was completed from medical records (clinical, immuno-virologic and evolutionary). Any VL > 1000 cp/ml after 6 months of antiretroviral therapy (ART) was considered as virologic failure. Data were captured and analysed using the EPI INFO 2002software. Chi-square test and the Fisher test were used to compare the proportions; a value of p ≤ 0.05 was considered significant. Results: 331 patients were treated with HIV-1 profile in 89% of cases. A proportion of 55% was married and 97% came from rural areas. 80% were either not or poorly educated. The median of age was 44 ± 11 years with a F/M ratio of 3.4. At baseline, 56% were symptomatic at stage 3 or 4 of WHO. They had severe immunosuppression with a median CD4 count of 217 ± 187 cells/mm3, the viral load was detectable in half of the patients with a median VL of 97,000 cp/ml ± 70,569. The antiretroviral regimen combined 2 NRTIs with 1 NNRTI in 88% of cases. The median of follow-up was estimated at 60 ± 43 months. The prevalence of virologic failure was 19%. This prevalence was associated with age less than 25 years (p = 0.04), late diagnosis (CD4 at baseline less than 200 cel/mm3 (p = 0.002), stage 3 or 4 WHO (p = 0.04) High viral load greater than 10,000 (p = 0.04) at baseline. Conclusion: These results suggest making the new therapeutic classes accessible for first-line treatment.

The Senegal National Malaria Control Programme (NMCP) introduced home-based malaria management for all ages, with diagnosis by rapid diagnostic test (RDT) and treatment with artemisinin-based combination therapy (ACT) in 2008, expanding to over 2,000 villages nationwide by 2014. With prise en charge à domicile (PECADOM), community health workers (CHWs) were available for community members to seek care, but did not actively visit households to find cases. A trial of a proactive model (PECADOM Plus), in which CHWs visited all households in their village weekly during transmission season to identify fever cases and offer case management, in addition to availability during the week for home-based management, found that CHWs detected and treated more cases in intervention villages, while the number of cases detected weekly decreased over the transmission season. The NMCP scaled PECADOM Plus to three districts in 2014 (132 villages), to a total of six districts in 2015 (246 villages), and to a total of 16 districts in 2016 (708 villages). A narrative case study with programmatic results is presented. During active sweeps over approximately 20 weeks, CHWs tested a mean of 77 patients per CHW in 2014, 89 patients per CHW in 2015, and 90 patients per CHW in 2016, and diagnosed a mean of 61, 61 and 43 patients with malaria per CHW in 2014, 2015 and 2016, respectively. The number of patients who sought care between sweeps increased, with a 104% increase in the number of RDTs performed and a 77% increase in the number of positive tests and patients treated with ACT during passive case detection. While the number of CHWs increased 7%, the number of patients receiving an RDT increased by 307% and the number of malaria cases detected and treated by CHWs increased 274%, from the year prior to PECADOM Plus introduction to its first year of implementation. Based on these results, approximately 700 additional CHWs in 24 new districts were added in 2017. This case study describes the process, results and lessons learned from Senegal’s implementation of PECADOM Plus, as well as guidance for other programmes considering introduction of this innovative strategy.

Summary Adding low-dose primaquine to malaria treatment reduced gametocyte carriage by 73%. Patients who received primaquine had more frequent hemoglobinuria and there was a greater reduction in haemoglobin concentration in G6PD-deficient patients. One patient who received primaquine developed moderately severe anemia., Introduction More information is needed about the safety of low-dose primaquine in populations where G6PD deficiency is common. Methods Adults with Plasmodium falciparum malaria were randomized to receive 1 of 3 artemisinin combination therapies (ACTs) with or without primaquine (0.25 mg/kg). Glucose-6-phosphate dehydrogenase (G6PD) status was determined using a rapid test. Patients were followed for 28 days to record hemoglobin concentration, adverse events, and gametocyte carriage. The primary end point was the change in Hb at day 7. Results In sum, 274 patients were randomized, 139 received an ACT alone, and 135 received an ACT + primaquine. The mean reduction in Hb at day 7 was similar in each group, a difference in the ACT + PQ versus the ACT alone group of −0.04 g/dL (95% confidence interval [CI] −0.23, 0.31), but the effect of primaquine differed according to G6PD status. In G6PD-deficient patients the drop in Hb was 0.63 g/dL (95% CI 0.03, 1.24) greater in those who received primaquine than in those who received an ACT alone. In G6PD-normal patients, the reduction in Hb was 0.22 g/dL (95% CI −0.08, 0.52) less in those who received primaquine (interaction P = .01). One G6PD normal patient who received primaquine developed moderately severe anaemia (Hb < 8 g/dL). Dark urine was more frequent in patients who received primaquine. Primaquine was associated with a 73% (95% CI 24–90) reduction in gametocyte carriage (P = .013). Conclusion Primaquine substantially reduced gametocyte carriage. However, the fall in Hb concentration at day 7 was greater in G6PD-deficient patients who received primaquine than in those who did not and one patient who received primaquine developed moderately severe anemia. Clinical Trial registration PACTR201411000937373 (www.pactr.org)

Background: In endemic areas, children develop slowly and naturally anti-Plasmodium antibodies and become semi-immune. Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine + amodiaquine (SPAQ) is a new strategy to reduce malaria morbidity in young children in West Africa. However, SMC may impact on the natural acquisition of anti-Plasmodium immunity. We evaluated the effect of SMC with SPAQ on malaria antibodies levels in Niger. Methods: This survey was conducted in areas with SMC since 2014 (Zinder district), without SMC (Dosso district) and with one year SMC 2016 (Gaya district). To assess the relationship between SMC and total Ig G Ab against P. falciparum antigens, we measured antibodies levels of two P.falciparum asexual stage vaccine candidate antigens (Circum Sporozoid Protein and Glutamate-rich Protein R2) in children aged 3–59 months and compared these levels in Zinder, Dosso and Gaya by enzyme-linked immune-sorbent assay (ELISA) on the elution extracted from the RDTs positive and negative cassette. Results: A total of 229 children aged 3-59 months were included in the analysis: 71 in Zinder, 77 in Dosso, and 81 in Gaya. In Zinder (CSP=17.5 and GLURP-R2=14.3) median antibodies levels observed were higher than in Gaya (CSP=7.7 and GLURP-R2=6.5) and Dosso (CSP=4.5 and GLURP-R2=3.6) (p

In the context of controlling intestinal parasites, accurate diagnosis is essential. Our objective was to evaluate the performance of new diagnostic kits compared to conventional microscopic methods in identifying intestinal parasites. Faeces collected in rural area in Senegal were subjected to several detection techniques. Thus, the sensitivity, specificity, positive and negative predictive values of new diagnostic techniques were compared to conventional merthiolate-iodine-formalin, conventional Bailenger and modified Ritchie. Furthermore, the kappa coefficient was calculated to evaluate the correlation between the new kit and those of modified Ritchie. Out of the 117 patients examined, 102 presented with a parasite, or prevalence of 87.1%. The Fumouze techniques proved to be as effective as the conventional methods in detecting flagellates and helminths with sensitivities ranging from 97 to 100%. However, conventional techniques were slightly more sensitive in identifying Endolimax nana and Blastocystis hominis. The correlation was nearly perfect (k = 0.83 and 1), respectively between Bailenger Fumouze, Iodesine Fumouze and modified Ritchie in identifying helminths while it was just acceptable (k = 0.27 and 0.28) in identifying B. hominis. The modified Ritchie technique routinely used in our laboratory remains a good diagnostic tool. However, the use of kit techniques was interesting when reading the pellet after concentration and the Colour KOP staining was a considerable contribution to the diagnosis of the vegetative forms. Therefore, it would be interesting to determine the cost of a stool test using Fumouze kit techniques to provide the most cost effective way.

BACKGROUND Since 2006, artemisinin-based combination therapies (ACT) have been used to treat uncomplicated Plasmodium falciparum malaria in Senegal, as recommended by WHO. Recently, decreased parasite clearance with artemisinin derivatives has been reported in Cambodia and Thailand. The effectiveness of artemisinin derivatives in Africa must be monitored. This study was conducted to evaluate the efficacy and the tolerability of three ACT widely used in Senegal. METHODS From October 2010 to February 2011, a descriptive and analytical sequential study was conducted in adults and children to evaluate these three combinations: artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DHAPQ). The study took place at the health posts of Deggo and Pikine and the health center of Guediawaye, in the suburbs of Dakar. The primary endpoint was the PCR-corrected adequate clinical and parasitological response (ACPR) at day 28 (D28); the secondary endpoints included ACPR at D42, clearance times for parasites, fever, and gametocytes, and the incidence of adverse events. RESULTS The study included 393 patients: 139 in the AL group, 130 in the ASAQ group, and 124 in the DHAPQ group. In the intent-to-treat population, PCR-corrected ACPR at day 28 was 92.8% in the AL, 89.2% in the ASAQ, and 91.1% in the DHAPQ (p = 0.58) groups, and in the per-protocol population, 98.4%, 98.3%, and 100% respectively (p = 0.39). At D42, ACPR was 99.2% in the AL, and 99.1% in each of the ASAQ and DHAPQ arms (p = 1). No early therapeutic failure (ETF) was observed. The combinations were well tolerated, with no serious adverse events reported during the follow-up period. CONCLUSION These combinations are still effective and well-tolerated. Continued monitoring is nonetheless essential to detect early artemisinin resistance in Africa.

Cerebral toxoplasmosis is caused by the protozoan Toxoplasma gondii because of reactivation of latent tissue cysts in the Acquired Immunodeficiency Syndrome (AIDS) patients with severe immunosuppression. The objective of this study was to evaluate the benefit of co-trimoxazole in presumptive and prevention of cerebral toxoplasmosis in Human Immunodeficiency Virus (HIV)/AIDS patients at Bobo-Dioulasso Hospital in Burkina Faso from June 2012 to October 2014. ELISA and ELFA were performed on serum for the quantitative determination of IgG and IgM anti-T. gondii, respectively. The seroprevalence of toxoplasmosis was 29.3%. No IgM antibodies for T. gondii were found. Six patients with Toxoplasma-specific antibodies presented cerebral toxoplasmosis. All patients were infected by HIV-1 with the median of CD4+ T lymphocytes at 141 cells/μl. No patient was under antiretroviral therapy. No case of cerebral toxoplasmosis was noted in patients receiving co-trimoxazole in prevention. Presumptive treatment of cerebral toxoplasmosis with co-trimoxazole was effective in all patients with a significant clinical improvement in 83.3%. These results attest the benefit of cotrimoxazole in cerebral toxoplasmosis treatment in countries where drug resources are limited when sulfadiazine is not available. Ours finding highlight the importance of establishing toxoplasmosis chemoprophylaxis to HIV with severe immunosuppression patients and positive Toxoplasma serology.

In Senegal, antimalarial drugs used in treatment and prevention of malaria are one of the main reasons for the current success in controlling malaria. However, the successful control of malaria is highly dependent on continued effectiveness of these drugs which may be compromised by the spread of drug resistance. Therefore, surveillance of drug resistance in the malaria parasites is essential. The objective of this pilot study was to test the feasibility of routinely sampled malaria rapid diagnostic tests (RDTs) at a national scale to assess the temporal changes in the molecular profiles of antimalarial drug resistance markers of Plasmodium falciparum parasites. Overall, 9,549 positive malaria RDTs were collected from 14 health facilities across the country. A limited random set of RDTs were analyzed regarding Pfcrt gene polymorphisms at codon 72–76. Overall, a high but varied prevalence (> 50%) of the wild-type CVMNK haplotype was observed including a higher CVMNK prevalence in the northern part (75%) compared with the southern part of the country (59%). With caution, the study provides a proof of concept that reuse of discarded P. falciparum positive RDTs can be applied in large-scale surveillance of antimalarial drug resistance.

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.

International audience; Gastrointestinal parasite infections represent one of the biggest public health problems in the world. Therefore, appropriate innovative tools are needed for assessing interventions to control these infections. This study aims to compare the performance of real-time polymerase chain reaction (PCR) assays to microscopic examination for detection of intestinal parasites. A direct microscopic examination and stool concentration was performed on 98 stool samples from patients attending Senegalese hospitals. Negative microscopic control samples were also collected in Nice and Marseille (France). Species-specific primers/probes were used to detect 20commongastrointestinal protozoans and helminths. Positive frequency and the sensitivity of each real-time PCR assay were compared with conventional microscopic examination. Real-time PCR was positive in 72 of 98 samples (73.5%), whereas microscopic examination was positive in 37 (37.7%) samples (P < 0.001). The real-time PCR assays were more sensitive than microscopy, with 57.4% (31/54) versus 18.5% (10/54), respectively, in the detection of parasites in asymptomatic patients (P < 0.05). In terms of polyparasitism, there were more coinfections detected by real-time PCR assays compared with microscopic methods (25.5% versus 3.06%). In comparison to parasite prevalence on individual samples, the results showed a perfect agreement (100%) between the two techniques for seven species, whereas discrepancies were observed for the others (agreement percentage varying from 64.2% to 98.9%). Real-time PCR appeared to be superior to microscopic examination for the detection of parasites in stool samples. This assay will be useful in diagnostic laboratories and in the field for evaluating the efficacy of mass drug administration programs.

OBJECTIVE Onychomycosis are a mycose of nail due to fungi. According to published data, they stands for half of all nail abnormalities. This survey was carried out to determine the frequency and the fungi involved in onychomycosis in Dakar. MATERIAL AND METHODS This study was carried out at the laboratory of parasitology and mycology at Le Dantec Hospital, in Senegal from January 2008 to December 2012 and includes 507 patients. RESULTS Onychomycosis were mycologically proved in 58.78% (298/507) of patients. Patient's age varies between 02 years to 82 years with a mean of 34.24 years. Women were more infected than men (sex-ratio was 2.38). Onychomycosis due to dermatophyte represented 37.92% (113/298) of patients and were essentially located on toes (60.71%). Distal and lateral subungual onychomycosis was the most frequent clinical form. Trichophyton rubrum and Trichophyton interdigitale were isolated respectively in 53.6% and 26.1% on toes. Yeasts represented 59.06% (176/298) of onychomycosis and were essentially located on fingernails (80.11%). Candida albicans represented 90.86% of isolated yeasts. Molds were isolated in nine cases (3.02%) and predominated in toenails. CONCLUSION Among 507 patients with onychopathy, this study identified 298 cases of onychomycosis. T. rubrum was the main dermatophytes and was isolated on toenails whereas on fingernails C. albicans was more often observed.

Breakdown by treatment. (DOCX 14 kb)

Anaemia grades (g/dl) of severity according to age and sex. (DOCX 14 kb)

Study characteristics: number of Hb measurements (total and by treatment) and measurement days. (DOCX 17 kb)

Background Anaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity. Methods Individual-patient data analysis based on nine randomized controlled trials of treatments of uncomplicated falciparum malaria from 13 sub-Saharan African countries. Risk factors for reduced haemoglobin (Hb) concentrations and anaemia on presentation and after treatment were analysed using mixed effect models. Results Eight thousand eight hundred ninety-seven patients (77.0%

Background: Polymorphism and antigenic variation of malaria parasites determine malaria episode and its outcome. The aim of this study was to determine Plasmodium falciparum genetic diversity over time in population with uncomplicated malaria under ACT exposure in Senegal. Method: P. falciparum isolates collected from 300 individuals with uncomplicated malaria infection living in a rural area of Senegal from 2004 to 2008 were analyzed by a nested PCR amplification of msp1 and msp2 genes to compare P. falciparum allelic families’ diversity. Results: Allelic variation in both msp1 and msp2 genes were identified in the samples analyzed. For msp1 gene, 10 different alleles were found (3 msp1_K1, 4 msp1_Mad20 and 3 msp1_Ro33). Among them msp1_k1 allelic family was predominant (>70%) over year. Regarding msp2 gene, 7.0 different alleles were found (3 msp2_3D7, 4 msp2_FC27). However msp2_FC27 strain was predominant, especially in 2006 and 2007. Monoclonal infections were more frequent for msp1 gene, in 2004 (48.78%) and 2005 (45.05%) and for msp2 gene than polyclonal ones. Conclusion: This study demonstrated some differences in the P. falciparum diversity between symptomatic subjects over years living in rural area in Senegal and this should be taken into account when designing msp1 or msp2 malaria vaccine.

L’objectif de cette etude etait de determiner la prevalence des helminthoses digestives, diagnostiquees dans un hopital universitaire de Dakar, Senegal. Sur 1 526 examens parasitologiques de selles, chez des patients avec symptomatologie evocatrice, un examen direct et des techniques de Ritchie et de Baerman ont ete realises entre 2004 et 2009 au laboratoire de parasitologie-mycologie de l’hopital A. Le Dantec de Dakar, 310 mettaient en evidence des helminthoses parasitologiques, soit une prevalence de 20,3 %. Les helminthes les plus frequemment retrouves etaient : Ascaris lumbricoides, Trichuris trichiura, Strongyloides stercoralis, Taenia saginata ou Taenia solium. Les hommes sont plus touches que les femmes avec respectivement 58 % et 42 %, soit un sex-ratio de 1,38. Les enfants âges de 10 a 15 ans etaient les plus touches, avec une prevalence de 34,5 %. Ces resultats confirment que les helminthoses intestinales sont endemiques a Dakar, d’ou la necessite de la mise en place de campagnes de deparasitage et d’education pour la sante, ainsi que d’une amelioration de l’environnement.

Background:Dihydroartemisinin-piperaquine (DP) is increasingly recommended for antimalarial treatment in many endemic countries; however, concerns have been raised over its potential under dosing in young children. We investigated the influence of different dosing schedules on DP's clinical efficacy.Methods and Findings:A systematic search of the literature was conducted to identify all studies published between 1960 and February 2013, in which patients were enrolled and treated with DP. Principal investigators were approached and invited to share individual patient data with the WorldWide Antimalarial Resistance Network (WWARN). Data were pooled using a standardised methodology. Univariable and multivariable risk factors for parasite recrudescence were identified using a Cox's regression model with shared frailty across the study sites. Twenty-four published and two unpublished studies (n = 7,072 patients) were included in the analysis. After correcting for reinfection by parasite genotyping, Kaplan-Meier survival estimates were 97.7% (95% CI 97.3%-98.1%) at day 42 and 97.2% (95% CI 96.7%-97.7%) at day 63. Overall 28.6% (979/3,429) of children aged 1 to 5 years received a total dose of piperaquine below 48 mg/kg (the lower limit recommended by WHO); this risk was 2.3-2.9-fold greater compared to that in the other age groups and was associated with reduced efficacy at day 63 (94.4% [95% CI 92.6%-96.2%], p

As a result of widespread antimalarial drug resistance, all African countries with endemic malaria have, in recent years, changed their malaria treatment policy. In Senegal, the health authorities changed from chloroquine (CQ) to a combination of sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ) in 2003. Since 2006, the artemisinin combination therapies (ACTs) artemether-lumefantrine (AL) and artesunate plus amodiaquine (AS/AQ) were adopted for uncomplicated malaria treatment. After several years of CQ withdrawal, the current study wished to determine the level of CQ resistance at the molecular level in selected sites in Senegal, because the scientific community is interested in using CQ again. Finger prick blood samples were collected from Plasmodium falciparum-positive children below the age of 10 years (N = 474) during cross-sectional surveys conducted in two study sites in Senegal with different malaria transmission levels. One site is in central Senegal, and the other site is in the southern part of the country. All samples were analyzed for single nucleotide polymorphisms (SNPs) in the P. falciparum CQ resistance transporter gene (Pfcrt; codons 72-76) using polymerase chain reaction (PCR) sequence-specific oligonucleotide probe (SSOP) enzyme-linked immunosorbent assay (ELISA) and real-time PCR methods. In total, the 72- to 76-codon region of Pfcrt was amplified in 449 blood samples (94.7%; 285 and 164 samples from the central and southern sites of Senegal, respectively). In both study areas, the prevalence of the Pfcrt wild-type single CVMNK haplotype was very high; in central Senegal, the prevalence was 70.5% in 2009 and 74.8% in 2010, and in southern Senegal, the prevalence was 65.4% in 2010 and 71.0% in 2011. Comparing data with older studies in Senegal, a sharp decline in the mutant type Pfcrt prevalence is evident: from 65%, 64%, and 59.5% in samples collected from various sites in 2000, 2001, and 2004 to approximately 30% in our study. A similar decrease in mutant type prevalence is noted in other neighboring countries. With the continued development of increased CQ susceptibility in many African countries, it may be possible to reintroduce CQ in the near future in a drug combination; it could possibly be given to non-vulnerable groups, but it demands close monitoring of possible reemergence of CQ resistance development.

With the paradigm shift from the reduction of morbidity and mortality to the interruption of transmission, the focus of malaria control broadens from symptomatic infections in children ≤ 5 years of age to include asymptomatic infections in older children and adults. In addition, as control efforts intensify and the number of interventions increases, there will be decreases in prevalence, incidence and transmission with additional decreases in morbidity and mortality. Expected secondary consequences of these changes include upward shifts in the peak ages for infection (parasitemia) and disease, increases in the ages for acquisition of antiparasite humoral and cellular immune responses and increases in false-negative blood smears and rapid diagnostic tests. Strategies to monitor these changes must include: 1] studies of the entire population (that are not restricted to children ≤ 5 or ≤ 10 years of age), 2] study sites in both cities and rural areas (because of increasing urbanization across sub-Saharan Africa) and 3] innovative strategies for surveillance as the prevalence of infection decreases and the frequency of false-negative smears and rapid diagnostic tests increases.

Summary In patients with malaria, parasitaemia is usually estimated by assuming 8000 white cell counts (WCC) per microlitre of blood. In a sample of 3044 African children under 5 years of age with uncomplicated falciparum malaria, parasitaemia estimated using standardised WCC was compared to parasitaemia calculated based on each child’s own WCC. The two methods produced comparable results. However, WCC were >8000 in under-fives with an inverse relationship with age, resulting in the standard approximation method significantly underestimating parasitaemia in the youngest age group and overestimating parasitaemia in the oldest age groups. Communication breve: Parasitemie estimee et reelle dans la malaria aigue non compliquee a Plasmodium falciparum chez les enfants africains de moins de cinq ans Chez les patients malariques, la parasitemie est generalement estimee a partir du seuil de 8.000 globules blancs par microlitre de sang. Dans un echantillon de 3.044 enfants africains de moins de cinq ans avec une malaria non compliquee aP. falciparum, la parasitemie estimee et reelle (calculee sur base du taux de globules blancs de chaque enfant), n’etaient en general pas significativement differentes. Cependant, il y avait une association inverse entre le taux de globules blancs et l’âge, resultant ainsi au fait que la methode d’approximation standard sous-estime nettement la parasitemie dans le groupe d’âge le plus jeune et surestime la parasitemie dans les groupes les plus âges. Comunicacion corta: Parasitemia estimada versus real en ninos Africanos menores de 5 anos con malaria aguda, no complicada por Plasmodium falciparum En pacientes con malaria, normalmente se estima la parasitemia asumiendo que hay 8000 leucocitos por microlitro de sangre. En una muestra de 3044 ninos africanos menores de cinco anos de edad, con malaria no complicada por falciparum, la parasitemia estimada y la parasitemia real (calculada basandose en los conteos leucocitarios de los propios ninos) en general no eran estadisticamente diferentes. Sin embargo habia una relacion inversa entre los conteos leucocitarios y la edad, de forma que el metodo de aproximacion estandar subestima significativamente la parasitemia en el grupo de edad de los mas jovenes y sobrestima la parasitemia entre los grupos de los mayores.

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

Position du probleme En zone de paludisme a transmission saisonniere, des etudes ont note une augmentation des deces maternels et de l’incidence de la pre-eclampsie. Ces observations suggerent l’existence d’un lien entre l’infection palustre et la survenue d’un probleme maternel ou fœtal a l’accouchement. Nous avons etudie ce lien dans une zone peri-urbaine au Senegal. Methodes L’etude a ete menee a la maternite « Roi-Baudouin » de Guediawaye, situee dans la banlieue de Dakar. Toutes les femmes ayant accouche a la maternite entre le 10 aout 1998 et le 15 decembre 1999 ont ete incluses. Nous avons recueilli les informations concernant leurs caracteristiques sociodemographiques, le deroulement de leur grossesse et l’observance d’une chimioprophylaxie anti-palustre. Pour chaque femme, le diagnostic de l’issue de l’accouchement a ete enregistre et une apposition placentaire a la recherche de parasite et de pigment malarique a ete realisee. Resultats Huit mille deux cent soixante-treize accouchements ont ete etudies: 5 597 (67,7 %) accouchements normaux, 1 214 (14,6%) hypotrophies fœtales et 1 462 (17,7%) accidents obstetricaux. La prevalence globale de l’infection palustre placentaire etait de 9,5% (785/8273). L’infection palustre a l’accouchement etait associee a la survenue d’une hypotrophie (OR ajuste = 2,06 (1,72-2,57)), de prematurite (OR ajuste = 3,51 (1,84-6,68)) et de deces perinatal (OR ajuste = 2,56 (1,65-3,97)). Nous n’avons pas retrouve de lien entre infection palustre et pathologie maternelle (dystocie, hemorragie, pre-eclampsie et eclampsie). Conclusions Bien que sans apparentes consequences pour la mere au moment de l’accouchement, l’infection palustre apparait grave pour le fœtus chez qui elle augmente le risque de deces perinatal et de faible poids de naissance par hypotrophie et par prematurite. Il est urgent de mettre en place des strategies efficaces de prevention du paludisme durant la grossesse pour reduire la mortalite et la morbidite perinatales.

BACKGROUND: In African rural settings, medically certified information on causes of death is largely lacking. The authors applied the verbal autopsy to identify causes of death before 15 years old in a rural area of Senegal where a demographic surveillance system is operating. METHODS: Between 1989 and 2000, a postmortem interview was conducted using a standardized questionnaire which was independently reviewed by two physicians who assigned the probable underlying cause of death. Discordant diagnoses were discussed by a panel of physicians. Causes of death were grouped into a few categories; cause-specific mortality rates and fractions were generated. RESULTS: Between 1989 and 1997, all-cause mortality fluctuated. Diarrhoeal diseases, malaria and acute respiratory infections explained between 30% and 70% of the mortality before 10 years of age. In children 1-9 years old, malaria death rate increased between 1989 and 1994 and thereafter did not change. The 1998-2000 years were marked by a peak in mortality, attributed to a meningitis outbreak in children more than one year old paralleled by an increase in death rate from fever of unknown origin, diarrhoeal diseases, and acute respiratory infections in children under 5 years. CONCLUSIONS: Verbal autopsy provided useful information on the mortality structure responsible for the 1998-2000 peak in mortality. It underlined that, outside outbreak situations, malaria was a leading cause of death for 1-9 year old children and that diarrhoea, acute respiratory infections, or fever from unknown origin accounted for up to 50% of the deaths among the children under 5 years.

In Senegal, a significant decrease of malaria transmission intensity has been noted the last years. Parasitaemia has become lower and, therefore, more difficult to detect by microscopy. In the context of submicroscopic parasitaemia, it has become relevant to rely on relevant malaria surveillance tools to better document malaria epidemiology in such settings. Serological markers have been proposed as an essential tool for malaria surveillance. This study aimed to evaluate the sero-epidemiological situation of Plasmodium falciparum malaria in two sentinel sites in Senegal. Cross-sectional surveys were carried out in Velingara (south Senegal) and Keur Soce (central Senegal) between September and October 2010. Children under 10 years old, living in these areas, were enrolled using two-level, random sampling methods. P. falciparum infection was diagnosed using microscopy. P. falciparum antibodies against circumsporozoite protein (CSP), apical membrane protein (AMA1) and merozoite surface protein 1_42 (MSP1_42) were measured by ELISA method. A stepwise logistic regression analysis was done to assess factors associated with P. falciparum antibodies carriage. A total of 1,865 children under 10 years old were enrolled. The overall falciparum malaria prevalence was 4.99% with high prevalence in Velingara of 10.03% compared to Keur Soce of 0.3%. Symptomatic malaria cases (fever associated with parasitaemia) represented 17.37%. Seroprevalence of anti-AMA1, anti-MSP1_42 and anti-CSP antibody was 38.12, 41.55 and 40.38%, respectively. The seroprevalence was more important in Velingara and increased with age, active malaria infection and area of residence. The use of serological markers can contribute to improved malaria surveillance in areas with declining malaria transmission. This study provided useful baseline information about the sero-epidemiological situation of malaria in Senegal and can contribute to the identification of malaria hot spots in order to concentrate intervention efforts. Trial registration number: PACTR201305000551876 ( http://www.pactr.org ).

Sequestration of the mature Plasmodium falciparum forms complicates detection, quantification and molecular analysis of human infections. Whether the circulating parasites represent all or only a subset of co-infecting genotypes is unclear. We have investigated this issue and compared placenta and peripheral blood msp1 and msp2 genotypes in 58 women delivering with an ICT-positive placenta in Guediawaye, Senegal. Most placenta (91%) and blood samples (98%) were multiply infected. Multiplicity of infection was positively correlated in both tissues. However, the placental and circulating genotype profiles differed markedly. Only 10% of matched peripheral blood/placenta samples had identical genotypes, whereas 74% had only partially concordant genotypes, with some alleles detected in both tissues, together with additional allele(s) detected in one tissue only. Eight women (14%) had totally discordant placental and peripheral blood genotypes. Thus, in the vast majority of cases, some sequestered genotypes remain hidden, undetected in the peripheral circulation, indicating that analysis of peripheral parasites generates a partial picture of a P. falciparum infection.

Identification of fungal clinical isolates is essential for therapeutic management. In resource-limited settings, identification mostly relies on biochemical tests whose sensitivity and specificity are known to be insufficient for identification of closely related or newly described species. MALDI-TOF has been shown in favored countries to be a reliable and powerful tool for microorganism identification, including yeasts. The aim of this study was to compare MALDI-TOF with routine identification procedures in a resource-poor context. A total of 734 clinical specimens (502 vaginal swabs, 147 oral swabs, 61 bronchoalveolar lavage fluids and 24 stool samples) have been tested in the mycology unit of Fann Hospital, Dakar, Senegal. Strains isolated from culture were identified by both conventional phenotypic methods (germ tube formation and biochemical panels) and MALDI-TOF Saramis/VITEK MS, bioMerieux, France. In addition to comparing the final identification, we determined the time of obtaining the results and the cost for both approaches. Overall, 218 (29.7 %) samples were positive for Candida. MALDI-TOF MS enabled the identification of 214 of the 218 strains isolated (98.1 %) at species level. Phenotypic approach yielded identification for 208 strains (95.4 %). Congruence between the tests was observed for 203 isolates. A discrepancy was observed for one isolate identified as Candida krusei with the phenotypic approach and Candida tropicalis with the MALDI-TOF. In addition, ten isolates identified at genus level by phenotypic methods were identified as C. glabrata (n = 8), C. tropicalis (n = 1) and C. parapsilosis (n = 1) by MALDI-TOF. The turnaround time for identification was

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.

BACKGROUND: Artemisinin-based combination therapy (ACT) is the recommended first-line therapy for uncomplicated Plasmodium falciparum malaria worldwide but decreased artemisinin susceptibility, phenotypically characterized as slow parasite clearance time (PCT), has now been reported in Southeast Asia. This makes it all too important to measure the dynamics of parasite clearance in African patients treated with ACT over time, to understand trends and detect changes early enough to intervene METHODS: Individual patient data from 27 clinical trials of artesunate-amodiaquine (ASAQ) vs comparators conducted between 1999 and 2009 were analysed for parasite clearance on modified intent-to-treat (ITT) basis. RESULTS: Overall 15,017 patients treated for uncomplicated P. falciparum malaria at 44 sites in 20 sub-Saharan African countries were included in the analysis; 51% (n=7,660) vs 49% (n=7,357) were treated with ASAQ and comparator treatments, respectively. Seventy-seven per cent (77%) were children under six years of age. The proportion of the patients treated with ASAQ with persistent parasitaemia on Day 2 was 8.6%, and 1.5% on Day 3. Risk factor for not clearing parasites on Day 2 and Day 3 calculated by multivariate logistic regression with random effect on site and controlling for treatment were: high parasitaemia before treatment was (adjusted risk ratios (AOR) 2.12, 95% CI 1.91-2.35, AOR 2.43, 95% CI 1.98-3.00, respectively); non-ACT treatment (p=0.001, for all comparisons). Anaemia (p=0.001) was an additional factor for Day 2 and young age (p=0.005) for Day 3.In patients treated with ASAQ in studies who had complete parasitaemia data every 24 hours up to Day 3 and additionally Day 7, the parasite reduction ratio was 93.9% by Day 1 and 99.9% by Day 2. Using the median parasitaemia before treatment (p0=27,125 μL) and a fitted model, the predicted PCT (pPCT = 3.614*ln (p0) - 6.135, r(2) = 0.94) in ASAQ recipients was 31 hours. CONCLUSION: Within the period covered by these studies, rapid Plasmodium falciparum clearance continues to be achieved in Sub-Saharan African patients treated with ACT, and in particular with ASAQ. The prediction formula for parasite clearance time could be a pragmatic tool for studies with binary outcomes and once-daily sampling, both for research and monitoring purposes.

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.