Randomized Trial of Vaccines for Zaire Ebola Virus Disease.

BACKGROUND: Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease. METHODS: We conducted two randomized, placebo-controlled trials - one involving adults and one involving children - to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26-MVA group), rVSVΔG-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSVΔG-ZEBOV-GP followed by rVSVΔG-ZEBOV-GP 56 days later (the rVSV-booster group). The primary end point was antibody response at 12 months, defined as having both a 12-month antibody concentration of at least 200 enzyme-linked immunosorbent assay units (EU) per milliliter and an increase from baseline in the antibody concentration by at least a factor of 4. RESULTS: A total of 1400 adults and 1401 children underwent randomization. Among both adults and children, the incidence of injection-site reactions and symptoms (e.g., feverishness and headache) was higher in the week after receipt of the primary and second or booster vaccinations than after receipt of placebo but not at later time points. These events were largely low-grade. At month 12, a total of 41% of adults (titer, 401 EU per milliliter) and 78% of children (titer, 828 EU per milliliter) had a response in the Ad26-MVA group; 76% (titer, 992 EU per milliliter) and 87% (titer, 1415 EU per milliliter), respectively, had a response in the rVSV group; 81% (titer, 1037 EU per milliliter) and 93% (titer, 1745 EU per milliliter), respectively, had a response in the rVSV-booster group; and 3% (titer, 93 EU per milliliter) and 4% (titer, 67 EU per milliliter), respectively, had a response in the placebo group (P<0.001 for all comparisons of vaccine with placebo). In both adults and children, antibody responses with vaccine differed from those with placebo beginning on day 14. CONCLUSIONS: No safety concerns were identified in this trial. With all three vaccine regimens, immune responses were seen from day 14 through month 12. (Funded by the National Institutes of Health and others; PREVAC ClinicalTrials.gov number, NCT02876328; EudraCT numbers, 2017-001798-18 and 2017-001798-18/3rd; and Pan African Clinical Trials Registry number, PACTR201712002760250.).

Causal effect of severe and non-severe malaria on dyslipidemia in African Ancestry individuals: A Mendelian randomization study.

BACKGROUND: Dyslipidemia is becoming prevalent in Africa, where malaria is endemic. Observational studies have documented the long-term protective effect of malaria on dyslipidemia; however, these study designs are prone to confounding. Therefore, we used Mendelian randomization (MR, a method robust to confounders and reverse causation) to determine the causal effect of severe malaria (SM) and the recurrence of non-severe malaria (RNM) on lipid traits. METHOD: We performed two-sample MR using genome wide association study (GWAS) summary statistics for recurrent non-severe malaria (RNM) from a Benin cohort (N = 775) and severe malaria from the MalariaGEN dataset (N = 17,000) and lipid traits from summary-level data of a meta-analyzed African lipid GWAS (MALG, N = 24,215) from the African Partnership for Chronic Disease Research (APCDR) (N = 13,612) and the Africa Wits-IN-DEPTH partnership for genomics studies (AWI-Gen) dataset (N = 10,603). RESULT: No evidence of significant causal association was obtained between RNM and high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol and triglycerides. However, a notable association emerged between severe malarial anaemia (SMA) which is a subtype of severe malaria and reduced HDL-C levels, suggesting a potential subtype-specific effect. Nonetheless, we strongly believe that the small sample size likely affects our estimates, warranting cautious interpretation of these results. CONCLUSION: Our findings challenge the hypothesis of a broad causal relationship between malaria (both severe and recurrent non-severe forms) and dyslipidemia. The isolated association with SMA highlights an intriguing area for future research. However, we believe that conducting larger studies to investigate the connection between malaria and dyslipidemia in Africa will enhance our ability to better address the burden posed by both diseases.

Prognostics of multiple malaria episodes and nutritional status in children aged 6 to 59 months from 2013 to 2017 in Dangassa, Koulikoro region, Mali.

BACKGROUND: In Africa, the relationship between childhood nutritional status and malaria remains complex and difficult to interpret. Understanding it is important in the improvement of malaria control strategies. This study aimed to assess the influence of nutritional status on the occurrence of multiple malaria episodes in children aged 6 to 59 months between 2013 and 2017 living in the village of Dangassa, Mali. METHODS: A community-based longitudinal study was conducted using cross-sectional surveys (CSSs) at the beginning (June) and end (November) of the malaria transmission season associated with passive case detection (PCD) at the Dangassa Community Health Centre. Children with asymptomatic malaria infection during cross-sectional surveys were selected and their malaria episodes followed by PCD. Malaria indicators in person-months were estimated using an ordinal-logistic model repeated on subjects during follow-up periods. RESULTS: The incidence rate (IR) during the period of high transmission (June to October), for 1 episode and for 2 + episodes peaked in 2013 with 65 children (IR = 95.73 per 1000 person-months) and 24 cases (IR = 35.35 per 1000 person-months), respectively. As expected, the risk of multiple episodes occurring during the period of high transmission was 3.23 compared to the period of low transmission after adjusting for other model parameters (95% CI [2.45-4.26], p = 0.000). Children with anaemia were at high risk of having multiple episodes (OR = 1.6, 95% CI [1.12-2.30], p = 0.011). However, the risk of having 2 + episodes for anemic children was higher during the period of low transmission (RR = 1.67, 95% CI [1.15-2.42], p = 0.007) compared to the period of high transmission (RR = 1.58, 95% CI [1.09-2.29], p = 0.016). The trend indicated that anemic and underweight children were significantly associated with multiple malaria episodes during the period of low transmission (p < 0.001). CONCLUSION: Results show that multiple episodes of malaria are significantly related to the nutritional status (anaemia and underweight) of the child during the two transmission seasons and more pronounced during the dry season (period of low transmission). Further research including other malnutrition parameters will be needed to confirm these findings.

Formative research to adapt the 'Diabetes Prevention Program- Power to Prevent' for implementation in Bamako, Mali.

BACKGROUND: There are few community-level behaviors change interventions for reducing diabetes and hypertension risk in Africa, despite increasing cases of type 2 diabetes and cardiovascular diseases. Thus, this study was designed to adapt the United States Centers for Disease Control and Prevention's "Diabetes Prevention Program Power to Prevent" (DPP-P2P) for use in low-income urban communities of Bamako, Mali. METHODS: Feedback was elicited on an initial French PowerPoint adaptation of the DPP-P2P session guidelines from stakeholders at the ministry of health, organizational partners, and medical care providers. Two community health centers in districts with high levels of diabetes or hypertension were selected to assist in developing the Malian adaptation. Focus groups were conducted with 19 community health workers (CHWs) of these centers. Based on feedback from these discussions, more graphics, demonstrations, and role plays were added to the PowerPoint presentations. The 19 CHWs piloted the proposed 12 sessions with 45 persons with diabetes or at-risk patients over a one-month period. Feedback discussions were conducted after each session, and changes in dietary and exercise habits were assessed pre and post participation in the program. This feedback contributed to finalization of a 14-session sequence. RESULTS: The DPP-P2P session guidelines were adapted for use by low-literacy CHWs, converting the written English guidelines into French PowerPoint presentations with extensive use of pictures, role plays and group discussions to introduce diabetes, diet, and exercise concepts appropriately for the Bamako context. CHWs recommendations for a strong family-oriented program led to expanded sessions on eliciting support from all adults in the household. The 45 participants in the pilot adaptation were enthusiastic about the program. At the end of the program, there were significant increases in the frequency of daily exercise, efforts to limit fat intake, and goals for more healthy diets and exercise levels. CONCLUSION: This study documents how an iterative process of developing the DPP-P2P adaptation led to the development of a culturally appropriate set of materials welcomed by participants and having promise for reaching the low-income, low-literacy population with or at risk for diabetes in Bamako, Mali.

Comparing vaccination coverage before and during COVID-19 pandemic in children under one year in the health district of commune V in Bamako, Mali.

INTRODUCTION: Although an essential frontline service in the prevention of child morbidity and mortality, there are indications that routine vaccinations have been disrupted during the COVID-19 pandemic. The present study aimed to compare vaccination coverage before COVID-19 in Mali in 2019 and during COVID-19 in 2020. OBJECTIVE: To compare vaccination coverages before COVID-19 in Mali in 2019 and during COVID-19 in 2020. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: We collected routine immunization data from 2019 to 2020 of children under one year in the health district of Commune V in Bamako which includes twelve community health centers (CSCom). RESULTS: Considering all vaccines together, coverage in 2019 was higher than in 2020 (88.7% vs. 71,6%) (p < 10- 3, Fig. 1). In 2020, low proportions of children vaccinated were observed in May (51.1%) two months after the first COVID-19 case in Mali on March 25, 2020. For all vaccines, the mean number of children vaccinated was significantly higher in 2019 (before COVID-19) as compared to 2020 (during COVID-19) (p < 0.05). However, in September and October 2019 BCG vaccine coverage was lower in 2019 as compared to 2020 (p < 10- 3). CONCLUSION: COVID-19 pandemic has affected routine childhood vaccine coverage in Commune V of Bamako, particularly in May 2020. Therefore, new strategies are needed to improve vaccine coverage in young children below 1.

Internally displaced persons in Mali facing the COVID 19 pandemic: A qualitative study / Les personnes déplacées internes au Mali face à la COVID-19 : une étude qualitative

Introduction: The COVID-19 pandemic has exacerbated an already existing security crisis leading to massive population displacements that have been taking place since 2012. Purpose of research: This study aims to explore the representations of internally displaced persons (IDPs) about the existence of COVID-19 and their knowledge about its signs, symptoms, modes of transmission and prevention measures. Methods: The study was qualitative and exploratory. Individual and group interviews were used to collect data from 52 IDPs in six sites in Bamako and Segou. All interviews were recorded and transcribed. Thematic content analysis and N-Vivo software were used. Results: The majority of IDPs believed in the existence of COVID-19 and had good knowledge of the signs, symptoms, modes of transmission and prevention measures against the disease. However, this was not sufficient for the adoption of public health measures. Among those who believed in its existence, some thought that it was a disease of the white and rich. Finally, a group of participants believed in conspiracy theories and claimed that the government and humanitarian organizations were only trying to make money through these campaigns. Conclusion: To our knowledge, this is the first study in Mali to explore IDPs' beliefs and knowledge about COVID-19. These results could inform policies, strategies, and interventions to combat COVID-19 in IDP sites and in the general population.

Introduction: Le Mali fait face depuis 2012 à une crise sécuritaire qui a entraîné des déplacements massifs des populations à laquelle s'est greffée la pandémie de la COVID-19. But de l'étude: Cette étude vise à explorer les représentations des personnes « déplacées internes ¼ (PDIs), c'est-à-dire des personnes forcées de fuir leur lieu d'origine, sur l'existence de la COVID-19 ainsi que leurs connaissances sur ses signes, ses symptômes, les modes de transmission et les mesures de prévention. Méthodes: L'étude est qualitative et exploratoire. Des entretiens individuels et en groupes ont permis de collecter les données auprès de 52 PDIs de six sites de Bamako et Ségou. Tous les entretiens ont été enregistrés et transcrits. L'analyse de contenu thématique et le logiciel NVivo ont été utilisés. Résultats: Dans leur majorité, les PDIs croyaient en l'existence de la COVID-19 et avaient de bonnes connaissances sur les signes, les symptômes, les modes de transmission et les mesures de prévention contre la maladie. Toutefois, cela n'a pas été suffisant pour l'adoption des mesures de santé publique. Parmi ceux qui croient en son existence, certains pensent que c'est toutefois une maladie des blancs et des riches. Enfin, un groupe de participants croyait plutôt en des théories du complot selon lesquelles le gouvernement et les organisations humanitaires ne chercheraient qu'à gagner de l'argent à travers ces campagnes. Conclusions: Il s'agit à notre connaissance de la première étude au Mali explorant les représentations et les connaissances des PDIs sur la COVID-19. Ces résultats pourraient éclairer les politiques, stratégies et interventions de lutte contre la COVID-19 dans les sites PDI et dans la population générale.

Efficacy of Cipargamin (KAE609) in a Randomized, Phase II Dose-Escalation Study in Adults in Sub-Saharan Africa With Uncomplicated Plasmodium falciparum Malaria.

BACKGROUND: Cipargamin (KAE609) is a potent antimalarial in a phase II trial. Here we report efficacy, pharmacokinetics, and resistance marker analysis across a range of cipargamin doses. These were secondary endpoints from a study primarily conducted to assess the hepatic safety of cipargamin (hepatic safety data are reported elsewhere). METHODS: This phase II, multicenter, randomized, open-label, dose-escalation trial was conducted in sub-Saharan Africa in adults with uncomplicated Plasmodium falciparum malaria. Cipargamin monotherapy was given as single doses up to 150 mg or up to 50 mg once daily for 3 days, with artemether-lumefantrine as control. Key efficacy endpoints were parasite clearance time (PCT), and polymerase chain reaction (PCR)-corrected and uncorrected adequate clinical and parasitological response (ACPR) at 14 and 28 days. Pharmacokinetics and molecular markers of drug resistance were also assessed. RESULTS: All single or multiple cipargamin doses ≥50 mg were associated with rapid parasite clearance, with median PCT of 8 hours versus 24 hours for artemether-lumefantrine. PCR-corrected ACPR at 14 and 28 days was >75% and 65%, respectively, for each cipargamin dose. A treatment-emerging mutation in the Pfatp4 gene, G358S, was detected in 65% of treatment failures. Pharmacokinetic parameters were consistent with previous data, and approximately dose proportional. CONCLUSIONS: Cipargamin, at single doses of 50 to 150 mg, was associated with very rapid parasite clearance, PCR-corrected ACPR at 28 days of >65% in adults with uncomplicated P. falciparum malaria, and recrudescent parasites frequently harbored a treatment-emerging mutation. Cipargamin will be further developed with a suitable combination partner. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov (NCT03334747).

Prevalence and Risk Factors Associated with Epilepsy in Six Health Districts of Mali: A Community-Based Cross-Sectional and Nested Case-Control Study.

INTRODUCTION: In resource-limited countries, epilepsy prevalence is underestimated and little is known about its risk factors. OBJECTIVES: This study aimed to determine the prevalence and risk factors for epilepsy in six health districts (HDs) in Mali. METHODS: A community-based cross-sectional and nested case-control study was conducted in 180 villages with the highest number of suspicious epilepsy cases (SECs) in the six study HDs. The SECs were observed as part of a Phase 1 screening conducted by community health workers. For the nested case-control study, one case was matched with at least one control based on residence and age. A case of epilepsy was a person diagnosed with convulsive epilepsy after clinical assessment by a neurologist. A control was a person diagnosed as normal after neurological assessment by a neurologist. Data were collected on sociodemographic characteristics, familial and medical history of epilepsy, consanguinity, place of delivery, preterm birth, length/type of delivery, and history of meningitis and cerebral malaria. A univariate and multivariate binomial logistic regression model was used to analyse factors associated with epilepsy. RESULTS: A total of 1,506 cases of epilepsy and 2,199 controls were enrolled in six HDs. The mean prevalence of epilepsy was 2‰, with the highest in Kenieba (3‰), a previously meso-endemic-onchocerciasis HD, and the lowest in Kadiolo (1.5‰), a hypo-endemic-onchocerciasis HD. Age (adjusted odds ratio [aOR] = 1.02 [95% confidence intervals [CI] 1.02-1.03]), history of cerebral malaria (aOR = 11.41 [95% CI 8.86-14.85]), history of meningitis (aOR = 1.95 [95% CI 1.16-3.29]), living in the HD of Tominian (aOR = 1.69 [95% CI 1.29-2.22]), delayed delivery (aOR = 3.21 [95% CI 2.07-5.07]), and dystocia (aOR = 3.37 [95% CI 2.03-5.73]) were all significantly associated with epilepsy. CONCLUSION: The prevalence of epilepsy (3‰) in a previously meso-endemic-onchocerciasis HD was much lower than the prevalence (13.35‰) documented in onchocerciasis endemic areas in 2,000. This decrease epilepsy prevalence in the previously meso-endemic region was induced by onchocerciasis, and the reduction was due to an effective community direct treatment with ivermectin programme. Cerebral malaria and obstetrical complications were the main risk factors for epilepsy and interventions improving malaria prevention/treatment and optimizing prenatal and obstetrical care need to be implemented to reduce incidence.

Trends in malaria epidemiological factors following the implementation of current control strategies in Dangassa, Mali.

BACKGROUND: Over the past decade, three strategies have reduced severe malaria cases and deaths in endemic regions of Africa, Asia and the Americas, specifically: (1) artemisinin-based combination therapy (ACT); (2) insecticide-treated bed nets (ITNs); and, (3) intermittent preventive treatment with sulfadoxine-pyrimethamine in pregnancy (IPTp). The rationale for this study was to examine communities in Dangassa, Mali where, in 2015, two additional control strategies were implemented: ITN universal coverage and seasonal malaria chemoprevention (SMC) among children under 5 years old. METHODS: This was a prospective study based on a rolling longitudinal cohort of 1401 subjects participating in bi-annual smear surveys for the prevalence of asymptomatic Plasmodium falciparum infection and continuous surveillance for the incidence of human disease (uncomplicated malaria), performed in the years from 2012 to 2020. Entomological collections were performed to examine the intensity of transmission based on pyrethroid spray catches, human landing catches and enzyme-linked immunosorbent assay (ELISA) testing for circumsporozoite antigen. RESULTS: A total of 1401 participants of all ages were enrolled in the study in 2012 after random sampling of households from the community census list. Prevalence of infection was extremely high in Dangassa, varying from 9.5 to 62.8% at the start of the rainy season and from 15.1 to 66.7% at the end of the rainy season. Likewise, the number of vectors per house, biting rates, sporozoites rates, and entomological inoculation rates (EIRs) were substantially greater in Dangassa. DISCUSSION: The findings for this study are consistent with the progressive implementation of effective malaria control strategies in Dangassa. At baseline (2012-2014), prevalence of P. falciparum was above 60% followed by a significant year-to-year decease starting in 2015. Incidence of uncomplicated infection was greater among children < 5 years old, while asymptomatic infection was more frequent among the 5-14 years old. A significant decrease in EIR was also observed from 2015 to 2020. Likewise, vector density, sporozoite rates, and EIRs decreased substantially during the study period. CONCLUSION: Efficient implementation of two main malaria prevention strategies in Dangassa substantially contribute to a reduction of both asymptomatic and symptomatic malaria from 2015 to 2020.

Variations in the use of malaria preventive measures among pregnant women in Guinea: a secondary analysis of the 2012 and 2018 demographic and health surveys.

BACKGROUND: Despite its effectiveness, the optimal use of the combination of insecticide-treated nets (ITN) and intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) remains low in malaria-endemic areas. Therefore, this study analyzed its variations and predictors in Guinea. METHODS: This study was a secondary analysis of the 2012 and 2018 Guinea Demographic and Health Surveys (DHS). It included women who had given birth 3 years before each DHS, slept on ITN and took at least one dose of SP. Use was complete if a pregnant woman slept on ITNs and took SP (at least two doses in 2012; at least three doses in 2018). Moran indices were used to determine spatial autocorrelation and classification methods to identify malaria preventive measures (MPM) predictors. RESULTS: In 2012, 60.88% of pregnant women had incomplete use of MPMs compared with 79.11% in 2018. Associated factors with incomplete MPMs in 2012 were as follows: having an indirect link with the head of household (AOR = 2.23, 95% CI 1.08-4.61) and performing at least 4 ANC visits (AOR = 0.66, 95% CI 0.44-0.99). In 2018: Living in households of 2 to 5 people (AOR = 0.54, 95% CI 0.36-0.80), have a man as the head of the household (AOR = 0.56, 95% CI 0.35-0.89), perform the first ANC in the second trimester of pregnancy (AOR = 0.74, 95% CI 0.54-0.99), perform at least 4 ANC visits (AOR = 0.47, 95% CI 0.36-0.62), have a job (AOR = 0. 67, 95% CI 0.50-0.88), give birth in a public health facility (AOR = 0.53, 95% CI 0.39-0.72) and the middle wealth quintile (AOR = 1.56, 95% CI 1.07-2.26). Analyses revealed a global autocorrelation (Moran index = 0.0009, p = 0.2349) and high-high clusters in Mamou in 2012. In 2018, autocorrelation was found (I Moran = 0.0169, p ≤ 0.05), with spatial clusters in 4 regions. CONCLUSION: The link with the head of household and the number of ANC visits were the main factors in MPMs. It is essential to implement strategies at the household level and health system level and monitor them to reduce inequality across regions.

Geographic Access and Maternal Health Services Utilization in Sélingué Health District, Mali.

INTRODUCTION: Maternal mortality is one of the main causes of death for women of childbearing age in Mali, and improving this outcome is slow, even in regions with relatively good geographic access to care. Disparities in maternal health services utilization can constitute a major obstacle in the reduction of maternal mortality in Mali and indicates a lack of equity in the Malian health system. Literature on maternal health inequity has explored structural and individual factors influencing outcomes but has not examined inequities in health facility distribution within districts with moderate geographic access. The purpose of this article is to examine disparities in education and geographic distance and how they affect utilization of maternal care within the Sélingué health district, a district with moderate geographic access to care, near Bamako, Mali. METHODS: We conducted a cross sectional survey with cluster sampling in the Sélingué health district. Maternal health services characteristics and indicators were described. Association between dependent and independent variables was verified using Kendall's tau-b correlation, Chi square, logistic regression with odds ratio and 95% confidence interval. Gini index and concentration curve were used to measure inequity. RESULTS: Most respondents were 20 to 24 years old. Over 31% of our sample had some education, 65% completed at least four ANC visits, and 60.8% delivered at a health facility. Despite this evidence of healthcare access in Sélingué, disparities within the health district contribute to inadequate utilization among approximately 40% of the women in our sample. The concentration index demonstrated the impact of inequity in geographic access, comparing women residing near and far from the referral care facility. CONCLUSION: Maternal health services underutilization, within a district with moderate geographic access, indicates that deliberate attention should be paid to addressing geographic access even in such a district.

Multiple Resistance Mechanisms to Pyrethroids Insecticides in Anopheles gambiae sensu lato Population From Mali, West Africa.

BACKGROUND: Insecticide-based vector control is responsible for reducing malaria mortality and morbidity. Its success depends on a better knowledge of the vector, its distribution, and resistance status to the insecticides used. In this paper, we assessed Anopheles gambiae sensu lato (A gambiae s.l.) population resistance to pyrethroids in different ecological settings. METHODS: The World Health Organization standard bioassay test was used to assess F0A gambiae s.l. susceptibility to pyrethroids. Biochemical Synergist assays were conducted with piperonyl butoxide (PBO), S,S,S-tributyl phosphotritioate, and diethyl maleate. L1014F, L1014S, and N1575Y knockdown resistance (kdr) mutations were investigated using TaqMan genotyping. RESULTS: Anopheles gambiae sensu lato was composed of Anopheles arabienisis, Anopheles coluzzii, and A gambiae in all study sites. Anopheles gambiae sensu lato showed a strong phenotypic resistance to deltamethrin and permethrin in all sites (13% to 41% mortality). In many sites, pre-exposure to synergists partially improved the mortality rate suggesting the presence of detoxifying enzymes. The 3 kdr (L1014F, L1014S, and N1575Y) mutations were found, with a predominance of L1014F, in all species. CONCLUSIONS: Multiple resistance mechanisms to pyrethroids were observed in A gambiae s.l. in Mali. The PBO provided a better partial restoration of susceptibility to pyrethroids, suggesting that the efficacy of long-lasting insecticidal nets may be improved with PBO.

Determinants of intermittent preventive treatment with sulfadoxine-pyrimethamine in pregnant women (IPTp-SP) in Mali, a household survey.

BACKGROUND: In malaria endemic regions, intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) is recommended for all pregnant women during prenatal consultation, from the fourth month of pregnancy up to the time of delivery. The Government of Mali is aiming for universal coverage of IPTp-SP. However, coverage is still low, estimated to be 18% for completion of three doses (IPTp-SP3). The objective of this study was to identify the factors that influence IPTp-SP adherence in the Health District of Sélingué, Mali. METHODS: This was a cross-sectional survey with 30 clusters, proportional to village size, with two stages of sampling. Data were collected electronically with Magpi software during face-to-face interviews/surveys. The data were analysed with SPSS version 20. A descriptive analysis and bivariate and multivariate logistic regression were performed. An equity analysis examined the effect of distance from health care facility on completion of three or more antenatal visits (ANC3 +) and three or more doses of intermittent preventive treatment (IPTp-SP3 +). RESULTS: Of the 1,021 women surveyed, 87.8% (n = 896) attended at least one ANC visit. Of these, 86.3% (n = 773) received at least one dose of IPTp-SP. Compliance with three or more doses of IPTp-SP was 63.7%. The determinants statistically related to ANC3 + were the early initiation of ANC (OR = 3.22 [1.22, 10.78]), and the presence of a community health centre (CHC) in the village (OR = 9.69 [1.09, 86.21]). The ability to read (OR = 1.60 [1.01, 2.55]), the early initiation of ANC (OR = 1.46 [1.06, 2.00], knowledge of the utility of the drug (OR = 2.38 [1.24, 4.57]), and knowledge of the recommended dose of the drug (OR = 6.11 [3.98, 9.39]) were related to completion of three or more treatments (IPTp-SP3 +). CONCLUSION: The early initiation of ANC was a positive determinant of the completeness of both ANC3 + and IPTp-SP3 + . This study shows that a successful implementation of the IPTp strategy can be achieved by improving access to prenatal care at community health facilities, and strengthening patient-provider communication to ensure adequate knowledge on dosing of IPTp-SP and the benefits to mother and child.

Estimating the potential impact of Attractive Targeted Sugar Baits (ATSBs) as a new vector control tool for Plasmodium falciparum malaria.

BACKGROUND: Attractive targeted sugar baits (ATSBs) are a promising new tool for malaria control as they can target outdoor-feeding mosquito populations, in contrast to current vector control tools which predominantly target indoor-feeding mosquitoes. METHODS: It was sought to estimate the potential impact of these new tools on Plasmodium falciparum malaria prevalence in African settings by combining data from a recent entomological field trial of ATSBs undertaken in Mali with mathematical models of malaria transmission. The key parameter determining impact on the mosquito population is the excess mortality due to ATSBs, which is estimated from the observed reduction in mosquito catch numbers. A mathematical model capturing the life cycle of P. falciparum malaria in mosquitoes and humans and incorporating the excess mortality was used to estimate the potential epidemiological effect of ATSBs. RESULTS: The entomological study showed a significant reduction of ~ 57% (95% CI 33-72%) in mosquito catch numbers, and a larger reduction of ~ 89% (95% CI 75-100%) in the entomological inoculation rate due to the fact that, in the presence of ATSBs, most mosquitoes do not live long enough to transmit malaria. The excess mortality due to ATSBs was estimated to be lower (mean 0.09 per mosquito per day, seasonal range 0.07-0.11 per day) than the bait feeding rate obtained from one-day staining tests (mean 0.34 per mosquito per day, seasonal range 0.28-0.38 per day). CONCLUSIONS: From epidemiological modelling, it was predicted that ATSBs could result in large reductions (> 30% annually) in prevalence and clinical incidence of malaria, even in regions with an existing high malaria burden. These results suggest that this new tool could provide a promising addition to existing vector control tools and result in significant reductions in malaria burden across a range of malaria-endemic settings.

Artemisinin-based combination therapy for uncomplicated Plasmodium falciparum malaria in Mali: a systematic review and meta-analysis.

BACKGROUND: Artemisinin-based combination therapy (ACT) was deployed in 2005 as an alternative to chloroquine and is considered the most efficacious treatment currently available for uncomplicated falciparum malaria. While widespread artemisinin resistance has not been reported to date in Africa, recent studies have reported partial resistance in Rwanda. The purpose of this study is to provide a current systematic review and meta-analysis on ACT at Mali study sites, where falciparum malaria is highly endemic. METHODS: A systematic review of the literature maintained in the bibliographic databases accessible through the PubMed, ScienceDirect and Web of Science search engines was performed to identify research studies on ACT occurring at Mali study sites. Selected studies included trials occurring at Mali study sites with reported polymerase chain reaction (PCR)-corrected adequate clinical and parasite response rates (ACPRcs) at 28 days. Data were stratified by treatment arm (artemether-lumefantrine (AL), the first-line treatment for falciparum malaria in Mali and non-AL arms) and analysed using random-effects, meta-analysis approaches. RESULTS: A total of 11 studies met the inclusion criteria, and a risk of bias assessment carried out by two independent reviewers determined low risk of bias among all assessed criteria. The ACPRc for the first-line AL at Mali sites was 99.0% (95% CI (98.3%, 99.8%)), while the ACPRc among non-AL treatment arms was 98.9% (95% CI (98.3%, 99.5%)). The difference in ACPRcs between non-AL treatment arms and AL treatment arms was not statistically significant (p = .752), suggesting that there are potential treatment alternatives beyond the first-line of AL in Mali. CONCLUSIONS: ACT remains highly efficacious in treating uncomplicated falciparum malaria in Mali. Country-specific meta-analyses on ACT are needed on an ongoing basis for monitoring and evaluating drug efficacy patterns to guide local malaria treatment policies, particularly in the wake of observed artemisinin resistance in Southeast Asia and partial resistance in Rwanda.

Testing configurations of attractive toxic sugar bait (ATSB) stations in Mali, West Africa, for improving the control of malaria parasite transmission by vector mosquitoes and minimizing their effect on non-target insects.

BACKGROUND: Application methods of |Attractive Toxic Sugar Baits (ATSB) need to be improved for wide-scale use, and effects on non-target organisms (NTOs) must be assessed. The goals of this study were to determine, at the village level, the effect of different configurations of bait stations to (1) achieve < 25% Anopheles mosquito vector daily feeding rate for both males and females and (2) minimize the effect on non-target organisms. METHODS: Dye was added to Attractive Sugar Bait Stations (without toxin) to mark mosquitoes feeding on the baits, and CDC UV light traps were used to monitor for marked mosquitoes. An array of different traps were used to catch dye marked NTOs, indicating feeding on the ASB. Stations were hung on homes (1, 2, or 3 per home to optimize density) at different heights (1.0 m or 1.8 m above the ground). Eight villages were chosen as for the experiments. RESULTS: The use of one ASB station per house did not mark enough mosquitoes. Use of two and three stations per house gave feeding rates above the 25% goal. There was no statistical difference in the percentage of marked mosquitoes between two and three stations, however, the catches using two and three bait stations were both significantly higher than using one. There was no difference in An. gambiae s.l. feeding when stations were hung at 1.0 and 1.8 m. At 1.8 m stations sustained less accidental damage. ASB stations 1.8 m above ground were fed on by three of seven monitored insect orders. The monitored orders were: Hymenoptera, Lepidoptera, Coleoptera, Diptera, Hemiptera, Neuroptera and Orthoptera. Using one or two stations significantly reduced percentage of bait-fed NTOs compared to three stations which had the highest feeding rates. Percentages were as follows: 6.84 ± 2.03% Brachycera followed by wasps (Hymenoptera: Vespidae) 5.32 ± 2.27%, and Rhopalocera 2.22 ± 1.79%. Hanging the optimal number of stations per house for catching mosquitoes (two) at 1.8 m above ground, limited the groups of non-targets to Brachycera, Chironomidae, Noctuoidea, Rhopalocera, parasitic wasps and wasps (Hymenoptera). Feeding at 1.8 m only occurred when stations were damaged. CONCLUSIONS: The goal of marking quarter of the total Anopheles population per day was obtained using 2 bait stations at 1.8 m height above the ground. This configuration also had minimal effects on non-target insects.

Hepatic safety and tolerability of cipargamin (KAE609), in adult patients with Plasmodium falciparum malaria: a randomized, phase II, controlled, dose-escalation trial in sub-Saharan Africa.

BACKGROUND: The novel anti-malarial cipargamin (KAE609) has potent, rapid activity against Plasmodium falciparum. Transient asymptomatic liver function test elevations were previously observed in cipargamin-treated subjects in two trials: one in malaria patients in Asia and one in volunteers with experimentally induced malaria. In this study, the hepatic safety of cipargamin given as single doses of 10 to 150 mg and 10 to 50 mg once daily for 3 days was assessed. Efficacy results, frequency of treatment-emerging mutations in the atp4 gene and pharmacokinetics have been published elsewhere. Further, the R561H mutation in the k13 gene, which confers artemisinin-resistance, was associated with delayed parasite clearance following treatment with artemether-lumefantrine in Rwanda in this study. This was also the first study with cipargamin to be conducted in patients in sub-Saharan Africa. METHODS: This was a Phase II, multicentre, randomized, open-label, dose-escalation trial in adults with uncomplicated falciparum malaria in five sub-Saharan countries, using artemether-lumefantrine as control. The primary endpoint was ≥ 2 Common Terminology Criteria for Adverse Events (CTCAE) Grade increase from baseline in alanine aminotransferase (ALT) or aspartate transaminase (AST) during the 4-week trial. RESULTS: Overall, 2/135 patients treated with cipargamin had ≥ 2 CTCAE Grade increases from baseline in ALT or AST compared to 2/51 artemether-lumefantrine patients, with no significant difference between any cipargamin treatment group and the control group. Cipargamin exposure was comparable to or higher than those in previous studies. Hepatic adverse events and general safety and tolerability were similar for all cipargamin doses and artemether-lumefantrine. Cipargamin was well tolerated with no safety concerns. CONCLUSIONS: This active-controlled, dose escalation study was a detailed assessment of the hepatic safety of cipargamin, across a wide range of doses, in patients with uncomplicated falciparum malaria. Comparison with previous cipargamin trials requires caution as no clear conclusion can be drawn as to whether hepatic safety and potential immunity to malaria would differ with ethnicity, patient age and or geography. Previous concerns regarding hepatic safety may have been confounded by factors including malaria itself, whether natural or experimental infection, and should not limit the further development of cipargamin. Trial registration ClinicalTrials.gov number: NCT03334747 (7 Nov 2017), other study ID CKAE609A2202.

Indoor and outdoor malaria transmission in two ecological settings in rural Mali: implications for vector control.

BACKGROUND: Implementation and upscale of effective malaria vector control strategies necessitates understanding the multi-factorial aspects of transmission patterns. The primary aims of this study are to determine the vector composition, biting rates, trophic preference, and the overall importance of distinguishing outdoor versus indoor malaria transmission through a study at two communities in rural Mali. METHODS: Mosquito collection was carried out between July 2012 and June 2016 at two rural Mali communities (Dangassa and Koïla Bamanan) using pyrethrum spray-catch and human landing catch approaches at both indoor and outdoor locations. Species of Anopheles gambiae complex were identified by polymerase chain reaction (PCR). Enzyme-Linked -Immuno-Sorbent Assay (ELISA) were used to determine the origin of mosquito blood meals and presence of Plasmodium falciparum sporozoite infections. RESULTS: A total of 11,237 An. gambiae sensu lato (s.l.) were collected during the study period (5239 and 5998 from the Dangassa and Koïla Bamanan sites, respectively). Of the 679 identified by PCR in Dangassa, Anopheles coluzzii was the predominant species with 91.4% of the catch followed by An. gambiae (8.0%) and Anopheles arabiensis (0.6%). At the same time in Koïla Bamanan, of the 623 An. gambiae s.l., An. coluzzii accounted for 99% of the catch, An. arabiensis 0.8% and An. gambiae 0.2%. Human Blood Index (HBI) measures were significantly higher in Dangassa (79.4%; 95% Bayesian credible interval (BCI) [77.4, 81.4]) than in Koïla Bamanan (15.9%; 95% BCI [14.7, 17.1]). The human biting rates were higher during the second half of the night at both sites. In Dangassa, the sporozoite rate was comparable between outdoor and indoor mosquito collections. For outdoor collections, the sporozoite positive rate was 3.6% (95% BCI [2.1-4.3]) and indoor collections were 3.1% (95% BCI [2.4-5.0]). In Koïla Bamanan, the sporozoite rate was higher indoors at 4.3% (95% BCI [2.7-6.3]) compared with outdoors at 2.4% (95% BCI [1.1-4.2]). In Dangassa, corrected entomological inoculation rates (cEIRs) using HBI were 13.74 [95% BCI 9.21-19.14] infective bites/person/month (ib/p/m) at indoor, and 18.66 [95% BCI 12.55-25.81] ib/p/m at outdoor. For Koïla Bamanan, cEIRs were 1.57 [95% BCI 2.34-2.72] ib/p/m and 0.94 [95% BCI 0.43-1.64] ib/p/m for indoor and outdoor, respectively. EIRs were significantly higher at the Dangassa site than the Koïla Bamanan site. CONCLUSION: The findings in this work may indicate the occurrence of active, outdoor residual malaria transmission is comparable to indoor transmission in some geographic settings. The high outdoor transmission patterns observed here highlight the need for additional strategies to combat outdoor malaria transmission to complement traditional indoor preventive approaches such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) which typically focus on resting mosquitoes.

Using community health workers as an alternative approach for epidemiological research on epilepsy in six health districts in Mali.

BACKGROUND: In Mali, the burden of epilepsy is underestimated due to socio-cultural barriers that keep most people with epilepsy out of the local health facilities. The objective of this study was to evaluate the performance of trained community health workers (CHWs) in identifying epilepsy cases (active case detection) as compared to the passive cases detection (PCD) during outpatient visits at the community health centers in the health districts (HDs) of Kolokani, Kayes, Kéniéba, Sikasso, Kadiolo, and Tominian. METHODS: A two-phase cross-sectional study was conducted from February to December 2019. In phase 1, trained CHWs conducted a census in 1017 villages organized into 174 community health centers which are part of the six study HDs to identify suspected epilepsy cases (SEC). Investigators used a modified epilepsy screening questionnaire from a validated standard questionnaire with the following three (3) questions: (i) Does or did the subject have a loss of consciousness and/or a loss of urine and/or drooling? (ii) Does or did the subject have an uncontrollable shake or abnormal movements of limb(s) (convulsions), with sudden onset and duration of a few minutes? (iii) Has or had the subject ever been told that he or she has epilepsy? During phase 2, neurologists confirmed the supposedly SEC (censed by the CHWs) in the first 30 villages with the highest number of SEC in each HD that were reported during phase 1. RESULTS: Of a total of 4830 SEC, 422 (10%) were identified by PCD during routine outpatient visits and 4408 (90%) through the active case detection (ACD) using the trained CHWs. The majority of SEC reported by the CHWs (PCD) were confirmed by neurologists, i.e. 82.9% (1645/1985). Phenobarbital was available in only 26 (14.9%) of the 174 surveyed health centers. Confirmed cases of epilepsy were reported in all the 174 health centers with prevalence varying from 91/100,00 to 285/100,000. CONCLUSION: Active case detection of epilepsy using trained CHWs is an effective approach for epidemiological studies of epilepsy in the community settings as compared to the passive approach.

Factors hindering health care delivery in nomadic communities: a cross-sectional study in Timbuktu, Mali.

BACKGROUND: In Mali, nomadic populations are spread over one third of the territory. Their lifestyle, characterized by constant mobility, excludes them from, or at best places them at the edge of, health delivery services. This study aimed to describe nomadic populations' characteristics, determine their perception on the current health services, and identify issues associated with community-based health interventions. METHODS: To develop a better health policy and strategic approaches adapted to nomadic populations, we conducted a cross-sectional study in the region of Timbuktu to describe the difficulties in accessing health services. The study consisted in administering questionnaires to community members in the communes of Ber and Gossi, in the Timbuktu region, to understand their perceptions of health services delivery in their settings. RESULTS: We interviewed 520 individuals, all members of the nomadic communities of the two study communes. Their median age was 38 years old with extremes ranging from 18 to 86 years old. Their main activities were livestock breeding (27%), housekeeping (26.4%), local trading (11%), farming (6%) and artisans (5.5%). The average distance to the local health center was 40.94 km and 23.19 km respectively in Gossi and Ber. In terms of barriers to access to health care, participants complained mainly about the transportation options (79.4%), the quality of provided services (39.2%) and the high cost of available health services (35.7%). Additionally, more than a quarter of our participants stated that they would not allow themselves to be examined by a health care worker of the opposite gender. CONCLUSION: This study shows that nomadic populations do not have access to community-based health interventions. A number of factors were revealed to be important barriers per these communities' perception including the quality of services, poverty, lifestyle, gender and current health policy strategies in the region. To be successful, future interventions should take these factors into account by adapting policies and methods.