Dyslipidemia in Adults with Type 2 Diabetes in a Rural Community in Ganadougou, Mali: A Cross-Sectional Study.

Dyslipidemia is a disorder where abnormally lipid concentrations circulate in the bloodstream. The disorder is common in type 2 diabetics (T2D) and is linked with T2D comorbidities, particularly cardiovascular disease. Dyslipidemia in T2D is typically characterized by elevated plasma triglyceride and low high-density lipoprotein cholesterol (HDL-C) levels. There is a significant gap in the literature regarding dyslipidemia in rural parts of Africa, where lipid profiles may not be captured through routine surveillance. This study aimed to characterize the prevalence and demo-graphic profile of dyslipidemia in T2D in the rural community of Ganadougou, Mali. We performed a cross-sectional study of 104 subjects with T2D in Ganadougou between November 2021 and March 2022. Demographic and lipid profiles were collected through cross-sectional surveys and serological analyses. The overall prevalence of dyslipidemia in T2D patients was 87.5% (91/104), which did not differ by sex (P = .368). High low-density lipoprotein cholesterol (LDL-C) was the most common lipid abnormality (78.9%, [82/104]). Dyslipidemia was associated with age and hypertension status (P = .013 and.036, respectively). High total and high LDL-C parameters were significantly associated with hypertension (P = .029 and .006, respectively). In low-resource settings such as rural Mali, there is a critical need to improve infrastructure for routine dyslipidemia screening to guide its prevention and intervention approaches. The high rates of dyslipidemia observed in Gandadougou, consistent with concomitant increases in cardiovascular diseases in Africa suggest that lipid profile assessments should be incorporated into routine medical care for T2D patients in African rural settings.

Type 2 diabetes prevalence, awareness, and risk factors in rural Mali: a cross-sectional study.

Diabetes is currently a crisis in sub-Saharan West Africa (SSWA) with dramatic implications for public health and national budgets prioritizing infectious diseases. There is limited recent literature about the prevalence, awareness, and risk factors for type 2 diabetes (T2D) in rural parts of SSWA. This study characterized T2D prevalence and risk factors for the rural Malian community of Nièna, which is situated in Mali's second-largest province of Sikasso. Between December 2020 and July 2021, a cross-sectional study of 412 participants was conducted in the Nièna community using clinical questionnaires and rapid diagnostic tests. Among 412 participants, there were 143 (34.7%) and 269 (65.3%) males and females, respectively. The overall prevalence of T2D in Nièna was 7.5% (31/412), and prevalence rates were 8.6% (23/269) and 5.6% (8/143) for females and males, respectively. Age, family history of diabetes, hypertension, waist circumference, and fetal macrosomia were significantly associated with T2D (p = 0.007, p < 0.001, p = 0.003, p = 0.013, and p < 0.001, respectively). Notably, 61.3% (19/31) of T2D subjects were unaware of their diabetic status before the study. Field surveys have considerable utility in driving T2D awareness in rural African 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.

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.

Template copy number and the sensitivity of quantitative PCR for Plasmodium falciparum in asymptomatic individuals.

BACKGROUND: The identification of asymptomatic individuals with Plasmodium falciparum infection is difficult because they do not seek medical treatment and often have too few asexual parasites detectable using microscopy or rapid diagnostic tests (≤ 200 parasites per µl). Quantitative PCR (qPCR) may provide greater sensitivity and permits estimation of the initial template DNA concentration. This study examined the hypothesis that qPCR assays using templates with higher copy numbers may be more sensitive for P. falciparum than assays based on templates with lower copy numbers. METHODS: To test this hypothesis, ten qPCR assays for DNA sequences with template copy numbers from 1 to 160 were compared using parasite DNA standards (n = 2) and smear-positive filter paper blots from asymptomatic smear-positive subjects (n = 96). RESULTS: Based on the testing of P. falciparum parasite DNA standards and filter paper blots, cycle threshold values decreased as the concentrations of template DNA and template copy numbers increased (p < 0.001). Likewise, the analytical and clinical sensitivities of qPCR assays for P. falciparum DNA (based on DNA standards and filter paper blots, respectively) increased with template copy number. Despite the gains in clinical sensitivity from increased template copy numbers, qPCR assays failed to detect more than half of the filter paper blots with low parasite densities (≤ 200 asexual parasites per µl). CONCLUSIONS: These results confirm the hypothesis that the sensitivity of qPCR for P. falciparum in the blood of individuals with asymptomatic infection increases with template copy number. However, because even the most sensitive qPCR assays (with template copy numbers from 32 to 160) detected fewer than 50% of infections with ≤ 200 asexual parasites per µl, the sensitivity of qPCR must be increased further to identify all smear-positive, asymptomatic individuals in order to interrupt transmission.

Clustering of asymptomatic Plasmodium falciparum infection and the effectiveness of targeted malaria control measures.

BACKGROUND: Because clustering of Plasmodium falciparum infection had been noted previously, the clustering of infection was examined at four field sites in West Africa: Dangassa and Dioro in Mali, Gambissara in The Gambia and Madina Fall in Senegal. METHODS: Clustering of infection was defined by the percent of persons with positive slides for asexual P. falciparum sleeping in a house which had been geopositioned. Data from each site were then tested for spatial, temporal and spatio-temporal clustering in relation to the prevalence of infection from smear surveys. RESULTS: These studies suggest that clustering of P. falciparum infection also affects the effectiveness of control interventions. For example, the clustering of infection in Madina Fall disappeared in 2014-2016 after vector control eliminated the only breeding site in 2013. In contrast, the temporal clustering of infection in Dioro (rainy season of 2014, dry season of 2015) was consistent with the loss of funding for Dioro in the second quarter of 2014 and disappeared when funds again became available in late 2015. The clustering of infection in rural (western) areas of Gambissara was consistent with known rural-urban differences in the prevalence of infection and with the thatched roofs, open eaves and mud walls of houses in rural Gambissara. In contrast, the most intense transmission was in Dangassa, where the only encouraging observation was a lower prevalence of infection in the dry season. Taken together, these results suggest: (a) the transmission of infection was stopped in Madina Fall by eliminating the only known breeding site, (b) the prevalence of infection was reduced in Dioro after financial support became available again for malaria control in the second half of 2015, (c) improvements in housing should improve malaria control by reducing the number of vectors in rural communities such as western Gambissara, and (d) beginning malaria control during the dry season may reduce transmission in hyperendemic areas such as Dangassa. CONCLUSIONS: From a conceptual perspective, testing for spatial, temporal and spatio-temporal clustering based on epidemiologic data permits the generation of hypotheses for the clustering observed and the testing of candidate interventions to confirm or refute those hypotheses.

"They Merely Prescribe and I Merely Swallow": Perceptions of Antenatal Pharmaceuticals and Nutritional Supplements Among Pregnant Women in Bamako, Mali.

OBJECTIVES: New international guidelines for antenatal care (ANC) will likely result in an increase in nutritional supplements and preventative medications for pregnant women in low and middle-income countries. Our objective was to understand how pregnant women in Mali perceive and experience multi-drug regimens in ANC in order to reveal factors that may influence uptake and adherence. METHODS: We conducted 29 semi-structured interviews and three focus groups with 21 pregnant women in two urban ANC sites in Bamako, Mali. Interviews focused on perception of purpose of ANC pharmaceuticals (particularly iron supplements, sulfadoxine-pyrimethamine as intermittent prevention of malaria and antiretroviral therapy for HIV), beliefs regarding efficacy and risk, and understanding of dosage and regimen. Transcripts were inductively coded and analyzed using the 'Framework' method. RESULTS: Participant descriptions of medication purpose, understanding of dosing, and beliefs about risks and efficacy varied widely, revealing that many pregnant women lack complete information about their medications. While some were burdened by side effects or complex regimens, women generally held favorable attitudes toward ANC medications. Responses suggest major barriers to adherence lie in the health system, namely insufficient patient-provider communication and inconsistent prescribing practices. CONCLUSIONS FOR PRACTICE: National health programs looking to improve maternal and child health with ANC pharmaceuticals need to place greater attention on patient counseling and consistent implementation of administration guidelines. Communication that positions pharmaceuticals as beneficial to mother and child, while presenting understandable information about purpose, dosing and potential side effects can promote uptake of multi-drug regimens and ANC services in general.

Expanding Research Capacity in Sub-Saharan Africa Through Informatics, Bioinformatics, and Data Science Training Programs in Mali.

Bioinformatics and data science research have boundless potential across Africa due to its high levels of genetic diversity and disproportionate burden of infectious diseases, including malaria, tuberculosis, HIV and AIDS, Ebola virus disease, and Lassa fever. This work lays out an incremental approach for reaching underserved countries in bioinformatics and data science research through a progression of capacity building, training, and research efforts. Two global health informatics training programs sponsored by the Fogarty International Center (FIC) were carried out at the University of Sciences, Techniques and Technologies of Bamako, Mali (USTTB) between 1999 and 2011. Together with capacity building efforts through the West Africa International Centers of Excellence in Malaria Research (ICEMR), this progress laid the groundwork for a bioinformatics and data science training program launched at USTTB as part of the Human Heredity and Health in Africa (H3Africa) initiative. Prior to the global health informatics training, its trainees published first or second authorship and third or higher authorship manuscripts at rates of 0.40 and 0.10 per year, respectively. Following the training, these rates increased to 0.70 and 1.23 per year, respectively, which was a statistically significant increase (p < 0.001). The bioinformatics and data science training program at USTTB commenced in 2017 focusing on student, faculty, and curriculum tiers of enhancement. The program's sustainable measures included institutional support for core elements, university tuition and fees, resource sharing and coordination with local research projects and companion training programs, increased student and faculty publication rates, and increased research proposal submissions. Challenges reliance of high-speed bandwidth availability on short-term funding, lack of a discounted software portal for basic software applications, protracted application processes for United States visas, lack of industry job positions, and low publication rates in the areas of bioinformatics and data science. Long-term, incremental processes are necessary for engaging historically underserved countries in bioinformatics and data science research. The multi-tiered enhancement approach laid out here provides a platform for generating bioinformatics and data science technicians, teachers, researchers, and program managers. Increased literature on bioinformatics and data science training approaches and progress is needed to provide a framework for establishing benchmarks on the topics.

Development of a data collection and management system in West Africa: challenges and sustainability.

BACKGROUND: Developing and sustaining a data collection and management system (DCMS) is difficult in malaria-endemic countries because of limitations in internet bandwidth, computer resources and numbers of trained personnel. The premise of this paper is that development of a DCMS in West Africa was a critically important outcome of the West African International Centers of Excellence for Malaria Research. The purposes of this paper are to make that information available to other investigators and to encourage the linkage of DCMSs to international research and Ministry of Health data systems and repositories. METHODS: We designed and implemented a DCMS to link study sites in Mali, Senegal and The Gambia. This system was based on case report forms for epidemiologic, entomologic, clinical and laboratory aspects of plasmodial infection and malarial disease for a longitudinal cohort study and included on-site training for Principal Investigators and Data Managers. Based on this experience, we propose guidelines for the design and sustainability of DCMSs in environments with limited resources and personnel. RESULTS: From 2012 to 2017, we performed biannual thick smear surveys for plasmodial infection, mosquito collections for anopheline biting rates and sporozoite rates and year-round passive case detection for malarial disease in four longitudinal cohorts with 7708 individuals and 918 households in Senegal, The Gambia and Mali. Major challenges included the development of uniform definitions and reporting, assessment of data entry error rates, unstable and limited internet access and software and technology maintenance. Strengths included entomologic collections linked to longitudinal cohort studies, on-site data centres and a cloud-based data repository. CONCLUSIONS: At a time when research on diseases of poverty in low and middle-income countries is a global priority, the resources available to ensure accurate data collection and the electronic availability of those data remain severely limited. Based on our experience, we suggest the development of a regional DCMS. This approach is more economical than separate data centres and has the potential to improve data quality by encouraging shared case definitions, data validation strategies and analytic approaches including the molecular analysis of treatment successes and failures.

Underreporting and Missed Opportunities for Uptake of Intermittent Preventative Treatment of Malaria in Pregnancy (IPTp) in Mali.

OBJECTIVES: To identify factors contributing to low uptake of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) in rural Mali. METHODS: We conducted secondary data analysis on Mali's 2012-2013 Demographic and Health Survey (DHS) to determine the proportion of women who failed to take IPTp-SP due to ineligibility or non-attendance at antenatal care (ANC). We also identified the proportion who reported taking other or unknown medications to prevent malaria in pregnancy and those who did not know if they took any medication to prevent malaria in pregnancy. We conducted qualitative interviews, focus groups and ANC observations in six rural sites in Mali's Sikasso and Koulikoro regions to identify reasons for missed opportunities. RESULTS: Our secondary data analysis found that reported IPTp-SP coverage estimates are misleading due to their dependence on a variable ("source of IPTp") that is missing 62% of its data points. Among all women who gave birth in the two years prior to the survey, 56.2% reported taking at least one dose of IPTp-SP. Another 5.2% reported taking chloroquine, 1.9% taking another drug to prevent malaria in pregnancy, 4.4% not knowing what drug they took to prevent malaria, and 1.1% not knowing if they took any drug to prevent malaria. The majority of women who did not receive IPTp-SP were women who also did not attend ANC. Our qualitative data revealed that many health centers neither administer IPTp-SP by directly observed therapy, nor give IPTp-SP at one month intervals through the second and third trimesters, nor provide IPTp-SP free of charge. Women generally reported IPTp-SP as available and tolerable, but frequently could not identify its name or purpose, potentially affecting accuracy of responses in household surveys. CONCLUSION: We estimate IPTp-SP uptake to be significantly higher than stated in Mali's 2012-13 DHS report. Increasing ANC attendance should be the first priority for increasing IPTp-SP coverage. Reducing cost and access barriers, ensuring that providers follow up-to-date guidelines, and improving patient counseling on IPTp-SP would also facilitate optimal uptake.

Clinical Research and the Training of Host Country Investigators: Essential Health Priorities for Disease-Endemic Regions.

The health-care needs and resources of disease-endemic regions such as west Africa have been a major focus during the recent Ebola outbreak. On the basis of that experience, we call attention to two priorities that have unfortunately been ignored thus far: 1) the development of clinical research facilities and 2) the training of host country investigators to ensure that the facilities and expertise necessary to evaluate candidate interventions are available on-site in endemic regions when and where they are needed. In their absence, as illustrated by the recent uncertainty about the use of antivirals and other interventions for Ebola virus disease, the only treatment available may be supportive care, case fatality rates may be unacceptably high and there may be long delays between the time potential interventions become available and it becomes clear whether those interventions are safe or effective. On the basis of our experience in Mali, we urge that the development of clinical research facilities and the training of host country investigators be prioritized in disease-endemic regions such as west Africa.

Sickle cell trait protects against Plasmodium falciparum infection.

Although sickle cell trait protects against severe disease due to Plasmodium falciparum, it has not been clear whether sickle trait also protects against asymptomatic infection (parasitemia). To address this question, the authors identified 171 persistently smear-negative children and 450 asymptomatic persistently smear-positive children in Bancoumana, Mali (June 1996 to June 1998). They then followed both groups for 2 years using a cohort-based strategy. Among the 171 children with persistently negative smears, the median time for conversion to smear-positive was longer for children with sickle trait than for children without (274 vs. 108 days, P < 0.001; Cox hazard ratio = 0.56, 95% confidence interval: 0.33, 0.96; P = 0.036). Similar differences were found in the median times to reinfection after spontaneous clearance without treatment (365 days vs. 184 days; P = 0.01). Alternatively, among the 450 asymptomatic children with persistently positive smears, the median time for conversion to smear-negative (spontaneous clearance) was shorter for children with sickle trait than for children without (190 vs. 365 days; P = 0.02). These protective effects of sickle trait against asymptomatic P. falciparum infection under conditions of natural transmission were demonstrable using a cohort-based approach but not when the same data were examined using a cross-sectional approach.

Improving malaria control in West Africa: interruption of transmission as a paradigm shift.

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.

Sahel, savana, riverine and urban malaria in West Africa: Similar control policies with different outcomes.

The study sites for the West African ICEMR are in three countries (The Gambia, Senegal, Mali) and are located within 750 km of each other. In addition, the National Malaria Control Programmes of these countries have virtually identical policies: (1) Artemisinin Combination Therapies (ACTs) for the treatment of symptomatic Plasmodium falciparum infection, (2) Long-Lasting Insecticide-treated bed Nets (LLINs) to reduce the Entomololgic Inoculation Rate (EIR), and (3) sulfadoxine-pyrimethamine for the Intermittent Preventive Treatment of malaria during pregnancy (IPTp). However, the prevalence of P. falciparum malaria and the status of malaria control vary markedly across the four sites with differences in the duration of the transmission season (from 4-5 to 10-11 months), the intensity of transmission (with EIRs from unmeasurably low to 4-5 per person per month), multiplicity of infection (from a mean of 1.0 to means of 2-5) and the status of malaria control (from areas which have virtually no control to areas that are at the threshold of malaria elimination). The most important priority is the need to obtain comparable data on the population-based prevalence, incidence and transmission of malaria before new candidate interventions or combinations of interventions are introduced for malaria control.