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Background Sub-Saharan Africa suffers from the highest maternal mortality ratio (MMR) in the world, with 542 deaths per 100,000 live births in 2017, relative to a global ratio of 211. Reducing gender inequities, increasing awareness regarding gender-based discrimination (GBD), and increasing the empowerment of women and girls have recently been recognized as prerequisites for improving maternal health. Previous studies have shown GBD to be related to gender health inequities. GBD results in low utilization of maternal health services and poorer quality of care. However, there is very limited research available on the relationship between GBD and maternal mortality in Sub-Saharan Africa (SSA). Methods We investigated the association between self-reported GBD and maternal mortality in an ecological study. We combined survey data from Demographic and Health Surveys (DHS) and from Afrobarometer across 78 sub-national regions, located in nine Sub-Saharan African countries. Data were analyzed using a random intercept two-level regression model, while controlling for relevant covariates at region- and country-level. Results The proportion of women who reported experiencing GBD varied between 0% in several regions in Benin, Mali, Senegal, South Africa, and Zimbabwe and 24·7% in Atacora, Benin. We identified a positive association between the proportion of women who reported experiencing GBD in a region in the past year and MMR. A 1% increase in the proportion of women experiencing GBD resulted in an increase of the MMR by nearly two, i.e., in two more maternal deaths per 100,000 live births. This association was even more pronounced after adjusting for region-level covariates, but did not change with the inclusion of country-level covariates. Conclusions Our findings show that the rate of self-reported GBD is associated with maternal mortality in a region, even after controlling for other factors that are known to influence maternal deaths. However, our model does not allow to rule out endogeneity. Further research is needed to unravel causal pathways between GBD and maternal mortality.

Aim: Our goal was to determine the histological profile of ENT lesions. Method: We carried out a retrospective and descriptive study in the ENT department and Cervico-Facial Surgery at the university hospital center Gabriel Toure (MALI) from 1995 to 2014. It made it possible to collect 450 cases. Result: We found a male predominance; 51.11% or a sex ratio of 1.04. The mean age of patients was 38.04 years with a standard deviation of 19.49 years and extremes of 3 months and 91 years. Benign tumors were the most frequent (154 cases or 34.22%) including 75 cases of adenomas and 43 cases of papillomas. Cancers accounted for 48.11% (or 153 cases) of all tumors and 34% of lesions. Carcinomas accounted for 81.04%, malignant lymphomas 13.72% and sarcomas 5.22% of cases. Among the 140 cases (31.11%) of inflammatory pseudotumors, we found 12 cases of tuberculosis and 15 cases of rhinoscleroma. Three (3) cases of dysplasia were observed. Conclusion: Interest should be focused on histology in order to initiate appropriate therapy.

Background Anti-malarial treatments effectiveness remains a critical challenge for control programmes. However, when drug efficacy is established, the dose is calculated based on a predefined weight according to the patient age. Based on the hypothesis that the standard assumption of weight according to the age when administering the drug could lead to a therapeutic failure potentially due to under-dosing (in the case of overweight) or over-dosing (in case of underweight). In this study, the relationship between weight status and malaria drug efficacy in clearing current Plasmodium falciparum infection and preventing reinfection after treatment was investigated. Methods Data were drown from a clinical trial conducted previously to investigate malaria drug efficacy in 749 children from Mali (2002–2004). Participants were treated either with artesunate + amodiaquine (AS + AQ, n1 = 250), artesunate + sulfadoxine–pyrimethamine (AS + SP, n2 = 248) or artesunate (AS, n3 = 251) and followed for 28 days after treatment. The World Health Organization (WHO) z-score was used to define weight status. A Chi square test was used to compare outcomes according to drugs, weight status and the dynamic of ALAT, ASAT, creatinine and haemoglobin level. Logistic regression models were developed to determine the effect of baseline parameters (weight status, aspartate transaminase, alanine aminotransferase, creatinine and haemoglobin level) on drug efficacy as per WHO criteria. Results Without molecular correction, in AS + AQ arm, the rate of adequate clinical and parasitological response (ACPR) was higher in the group of underweight children 94.74% compared to children with normal and overweight (91.24% and 80.43% respectively, p = 0.03). After PCR correction, treatment efficacy was similar in the three groups of patients and was above 98% (p = 0.4). Overweight was observed to have no impact on recrudescence. However, it was associated with an increased risk of new infections in the (AS + AQ) arm (OR = 0.21, 95% CI [0.06; 0.86], p = 0.03). Conclusions The findings suggest that weight deficiency has no deleterious effect on anti-malarial drug efficacy. An increase in the rate of reinfection in overweight children treated by AS + AQ should be further explored in larger studies.

Summary Background Artemether–lumefantrine and artesunate–amodiaquine are used as first-line artemisinin-based combination therapies (ACTs) in west Africa. Pyronaridine–artesunate and dihydroartemisinin–piperaquine are potentially useful for diversification of ACTs in this region, but further safety and efficacy data are required on malaria retreatment. Methods We did a randomised, multicentre, open-label, longitudinal, controlled phase 3b/4 clinical trial at seven tertiary centres in Burkina Faso, Guinea, and Mali. Eligible participants for first malaria episode and all retreatment episodes were adults and children aged 6 months and older with microscopically confirmed Plasmodium spp malaria (>0 to

We are very grateful to the editor, John Hoddinott, and two anonymous referees, Hoyt Bleakley, Lauwrence Katz, Maria Kuecken, Nigel Rice, Andrew Street, Marie-Anne Valfort and numerous seminar participants for helpful comments and advice. We especially thank the children of Diankabou and their families for their cooperation. We are also grateful to Diankabou school teachers, the Malaria Research and Training Center employees for expert research assistance, for help acquiring the necessary data and for answering our many questions. In particular, we would like to thank Prof. Abdoulaye Djimdé Dr Alasseini Balam, Dr Yamoussa Keita, Dr Abdoul Karim Sangaré Saïla Doumbo, Ismaila Théra; and the Department of Immunology of Stockholm University, especially Stéphanie Bostrm, Leif Rogell and Marita Troye Blomberg. We thank the European Research Council (ERC Starting Grant DU 283953), the French School of Public Health, the Fondation pour les Études et Recherches sur le Développement International and University Paris 1 for financial support. This work also benefited from the support of the French National Research Agency, as part of the programme ‘Investissements d'avenir’, ANR-10-LABX-14–01. The usual caveat applies. International audience This article examines the influence of malaria on human capital accumulation in the village of Diankabou in Mali. To account for malaria endogeneity and its interaction with unobservable risk factors, we exploit natural variations in malaria immunity across individuals of several sympatric ethnic groups—the Fulani and the non-Fulani—who differ in their susceptibility to malaria. The Fulani are known to be less susceptible to malaria infections, despite living with a similar malaria transmission intensity to those seen among other ethnic groups. We also use natural variation of malaria intensity in the area (during and after the malaria transmission season) and utilise this seasonal change as a treatment. We found that malaria has an impact on cognitive and educational outcomes in this village.

BackgroundWHO recommended seasonal malaria chemoprevention (SMC) in 2012 for Sahel countries in Africa with the aim to reduce malaria among children under 5 years old by using sulphadoxine-pyrimethamine and amodiaquine (SP+AQ). This strategy was scaled up in Mali from 2012. The use of millions of doses of SP+AQ could generate potential Plasmodium falciparum resistance in mutant parasites. The aim of this study was to monitor the prevalence of Pfdhfr +Pfdhps+pfcrt +pfmdr1 mutations in parasites infecting the target population.MethodsTwo cross-sectional surveys were conducted before (August 2012, n=662) and after (June 2014, n=670) a pilot implementation of SMC in the health district of Koutiala. Children aged 3–59 months received 3 and 4 rounds of curative doses of SP+AQ over two malaria seasons in 2012 and 2013, respectively. Genotypes of P. falciparum Pfdhfr codons 51, 59, 108 and 164; Pfdhps codons 437 and 540, Pfcrt codon 76 and Pfmdr1 codon 86 were analysed by PCR on DNA of parasites from SMC population blood samples (after and before) and non-SMC patients aged 7 years or above (November 2014, n=500).ResultsIn the SMC population 191 and 85 children before and after SMC implementation, respectively, were included in’the molecular analysis. In the non-SMC patients, 220 were’successfully PCR analysed. In the SMC population, the’prevalence of the six-mutation Pfcrt [Pfdhfr-dhps quintuple +Pfcrt-76T] genotype increased significantly after SMC implementation, from 0.0% to 7.1% (p=0.0008). The post-intervention prevalence of the six-mutation Pfmdr1 [Pfdhfr-dhps quintuple +Pfmdr1–86Y] and the seven-mutation Pfcrt +Pfmdr1 [Pfdhfr-dhps quintuple +Pfmdr1–86Y+Pfcrt-76T] genotypes were both 1.2% among the SMC population. No six-mutation and seven-mutation genotypes were observed among SMC population at baseline nor in the non-SMC patient population (p=0.30).ConclusionSMC increased the prevalence of the six-mutation Pfcrt genotype of P. falciparum that can lead to resistance in a population exposed to SMC with SP+AQ.

Objectif. L’objectif de cette etude etait de determiner la prevalence des helminthes intestinaux et de Schistosoma haematobium avant et apres la saison des pluies a Pongonon, Mali. Methode. Deux etudes transversales ont ete effectuees en juillet et novembre 2007. Les sujets âges de 1 an et plus constituaient la population d’etude. La technique de Kato-Katz et celle de la filtration sur papier Wattman ont ete utilisees pour la recherche, respectivement, des œufs d’helminthes intestinaux dans les selles et des œufs de S. haematobium dans les urines. Resultats. Sur un total de 304 volontaires inclus en debut de saison pluvieuse (juillet), 278 personnes ont ete revues en fin de cette saison (novembre). Il y avait plus d’infections par les helminthes intestinaux en novembre (8,3 %) qu’en juillet (2,9 %) ( p = 0,01). La prevalence de S. haematobium etait nulle en juillet et de 7,6 % en novembre ( p < 0,001). Les prevalences des d’helminthes intestinaux chez les enfants et les adultes etaient comparables mais celle de l’infection par S. haematobium etait plus elevee chez les enfants de 6-16 ans (17/153) que chez les adultes (2/74) ( p = 0,02). Conclusion. La prevalence des helminthes intestinaux et celle de la bilharziose a S. haematobium sont plus elevees a la fin de la saison des pluies aussi bien chez les enfants que chez les adultes, qui pourraient ainsi etre des reservoirs potentiels de parasites. Pour une lutte efficiente, le programme de chimiotherapie de masse doit cibler les periodes de forte excretion d’œufs de parasite, mais aussi s’etendre aux adultes dans certaines zones du pays.

Contains fulltext : 89111.pdf (Publisher’s version ) (Closed access) Sulfadoxine-pyrimethamine (SP) is currently the drug of choice for intermittent preventive treatment of Plasmodium falciparum both in pregnancy and infancy. A prolonged parasite clearance time conferred by dhfr and dhps mutations is believed to be responsible for increased gametocyte prevalence in SP treated individuals. However, using a direct feeding assay in Mali, we showed that gametocytes present in peripheral venous blood post-SP treatment had reduced infectivity for Anopheles gambiae sensu stricto (ss) mosquitoes. We investigated the potential mechanisms involved in the dhfr and dhps quintuple mutant NF-135 and the single dhps 437 mutant NF-54. Concentrations of sulfadoxine (S) and pyrimethamine (P) equivalent to the serum levels of the respective drugs on day 3 (S=61 microg/ml, P=154.7 ng/ml) day 7 (S=33.8 microg/ml, P=66.6 ng/ml) and day 14 (S=14.2 microg/ml, P=15.7 ng/ml) post-SP treatment were used to study the effect on gametocytogenesis, gametocyte maturation and infectivity to Anopheles stephensi mosquitoes fed through an artificial membrane. The drugs readily induced gametocytogenesis in the mutant NF-135 strain but effectively killed the wild-type NF-54. However, both drugs impaired gametocyte maturation yielding odd-shaped non-exflagellating mature gametocytes. The concomitant ingestion of both S and P together with gametocytemic blood-meal significantly reduced the prevalence of oocyst positivity as well as oocyst density when compared to controls (P

Background Plasmodium falciparum resistance to artemisinin has been reported in South-East Asia. Long half-life drugs are increasingly being used for malaria prevention. The potential spread of parasite resistance to these regimens is real and makes regular efficacy surveillance a priority. Methods From August to December 2004 and July to December 2005, a randomized open label trial of sulphadoxine-pyrimethamine (SP) + artesunate (AS) versus SP + amodiaquine (AQ), and SP alone, was conducted in two villages of Mali. PCR was used to distinguish new infections from recrudescent P. falciparum infections. Patients were followed for 28 days to assess treatment efficacy. Results Overall 912 children aged between six to 59 months, with uncomplicated P. falciparum malaria were recruited. Baseline characteristics were similar in the three treatment arms. Crude ACPRs were 94.9%; 98.6% and 93.5% for SP + AS; SP + AQ and SP alone arms respectively (SP + AS versus SP + AQ, p = 0.01; SP + AS versus SP, p = 0.5; SP + AQ versus SP, p = 0.001). After PCR adjustment, cACPRs were 99%; 100% and 97.2% for SP + AS; SP + AQ and SP alone arms, respectively (SP + AS versus SP + AQ, p = 0.25; SP + AS versus SP, p = 0.12; SP + AQ versus SP, p = 0.007). Conclusion Sulphadoxine-pyrimethamine + amodiaquine therapy was as efficacious as sulphadoxine-pyrimethamine + artesunate, but more efficacious than sulphadoxine-pyrimethamine alone in the treatment of uncomplicated P. falciparum malaria in Mali.

Background The detailed assessment of the QT and corrected QT (QTc) intervals prolongation is recommended when testing new drugs. The electrocardiograph automatically displays generally reliable values of the QT interval and corrected QT but morphological variations of the T wave may cause reading errors, hence the use of the manual measurement as an alternative method. Our objective was to evaluate the correlation between the automatic and manual measurement of QT values. Methods In Kolle from March 2012 to December 2015, an open randomised, phase III-b/IV study comparing dihydroartemisinine-piperaquine, pyronaridine-artesunate and artemether-lumefantrine was conducted. An electrocardiograph cartridge 12 electrodes coupled to a computer with the Tele Touch software was used for the electrocardiogram on Day 0 before the study drugs administration and on Day 2, 2–4 hours after the administration of the last dose of the antimalarial. The manual measurement of QT and QTc was made using the Bazett method [QTcB_m=(Number leaded×0.04×QTcF) / QTcB]. For prolonged QTc cases on Day 2, another measurement was done during the next scheduled visit (Days 7, 14, 21, 28, 35 and 42) until the QTc normalisation. Results A total of 764 ECG was recorded with 398 participants. Different automatic and manual values of QT and QTc are scattered around different medium. Comparisons of different values of QT (p=0.1245) and QTc (p Conclusions Our results indicate no perfect match between automatic and manual methods for QT and QTc. Manual reading remains important to correct any machine errors during clinical studies.

Background Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP)+amodiaquine (AQ) is being scaled up in countries of the Sahel in West Africa. However, the potential development of Plasmodium falciparum resistance to the respective component drugs is a major concern. Methods Two cross-sectional surveys were conducted before (August 2012) and after (June 2014) a pilot implementation of SMC in Koutiala, Mali. Children aged 3–59 months received 7 rounds of curative doses of SP+AQ over two malaria seasons. Genotypes of P. falciparum dhfr codons 51, 59 and 108; dhps codons 437 and 540, pfcrt codon 76 and pfmdr1codon 86 were analysed by PCR on DNA from samples collected before and after SMC, and in non-SMC controls. Results In the SMC population 191/662 (28.9%) and 85/670 (13.7%) of children were P. falciparum- positive by microscopy and were included in the molecular analysis before (2012) and after SMC implementation (2014), respectively. In the control population 220/310 (71%) were successfully PCR analysed. In the SMC children the prevalence of all molecular markers of SP resistance increased significantly after SMC including the dhfr-dhps quintuple mutant genotype, which was 1.6% before but 7.1% after SMC (p=0.02). The prevalence of Pfmdr1–86Y significantly decreased from 26.7% to 15.3% (p=0.04) while no significant change was seen for pfcrt K76T. In 2014, prevalence of all molecular markers of SP resistance were significantly higher among SMC children compared to the non-SMC control population (p Conclusions SMC increased the prevalence of molecular markers of P. falciparum resistance to SP in the treated children. However, there was no significant flow of these resistance genes into the general parasite population after 2 years and 7 rounds of SMC.

This study aimed to compare the epidemiology of Rickettsia felis infection and malaria in France, North Africa, and sub-Saharan Africa and to identify a common vector. Blood specimens from 3,122 febrile patients and from 500 nonfebrile persons were analyzed for R. felis and Plasmodium spp. We observed a significant linear trend (p

Background Seasonal malaria chemoprevention (SMC) with sulphadoxine-pyrimethamine (SP) plus amodiaquine (AQ) is being scaled up in Sahelian countries of West Africa. However, the potential development of Plasmodium falciparum resistance to the respective component drugs is a major concern. Methods Two cross-sectional surveys were conducted before (August 2012) and after (June 2014) a pilot implementation of SMC in Koutiala, Mali. Children aged 3–59 months received 7 rounds of curative doses of SP plus AQ over two malaria seasons. Genotypes of P. falciparum Pfdhfr codons 51, 59 and 108; Pfdhps codons 437 and 540, Pfcrt codon 76 and Pfmdr1codon 86 were analyzed by PCR on DNA from samples collected before and after SMC, and in non-SMC patient population as controls (November 2014). Results In the SMC population 191/662 (28.9%) and 85/670 (12.7%) of children were P. falciparum positive by microscopy and were included in the molecular analysis before (2012) and after SMC implementation (2014), respectively. In the non-SMC patient population 220/310 (71%) were successfully PCR analyzed. In the SMC children, the prevalence of all molecular markers of SP resistance increased significantly after SMC including the Pfdhfr-dhps quintuple mutant genotype, which was 1.6% before but 7.1% after SMC (p = 0.02). The prevalence of Pfmdr1-86Y significantly decreased from 26.7% to 15.3% (p = 0.04) while no significant change was seen for Pfcrt 76T. In 2014, prevalence of all molecular markers of SP resistance were significantly higher among SMC children compared to the non-SMC population patient (p < 0.01). No Pfdhfr-164 mutation was found neither at baseline nor post SMC. Conclusion SMC increased the prevalence of molecular markers of P. falciparum resistance to SP in the treated children. However, there was no significant increase of these markers of resistance in the general parasite population after 2 years and 7 rounds of SMC.

Serological surveys are essential to quantify immunity in a population but serological cross-reactivity often impairs estimates of the seroprevalence. Here, we show that modeling helps addressing this key challenge by considering the important cross-reactivity between Chikungunya (CHIKV) and O’nyong-nyong virus (ONNV) as a case study. We develop a statistical model to assess the epidemiology of these viruses in Mali. We additionally calibrate the model with paired virus neutralization titers in the French West Indies, a region with known CHIKV circulation but no ONNV. In Mali, the model estimate of ONNV and CHIKV prevalence is 30% and 13%, respectively, versus 27% and 2% in non-adjusted estimates. While a CHIKV infection induces an ONNV response in 80% of cases, an ONNV infection leads to a cross-reactive CHIKV response in only 22% of cases. Our study shows the importance of conducting serological assays on multiple cross-reactive pathogens to estimate levels of virus circulation., O’nyong nyong and Chikungunya virus are arboviruses present in Africa but their prevalence is unknown, partly due to high antibody cross-reactivity with one another. Here, the authors develop a statistical model that accounts for cross-reactivity to characterise circulation of both viruses from seroprevalence surveys.