Impact of intermittent preventive treatment with sulphadoxine-pyrimethamine targeting the transmission season on the incidence of clinical malaria in children in Mali

<p>Abstract</p> <p>Background</p> <p>Recent studies have shown that intermittent preventive malaria treatment (IPT) in infants in areas of stable malaria transmission reduces malaria and severe anaemia incidence. However in most areas malaria morbidity and mortality remain high in older children.</p> <p>Methods</p> <p>To evaluate the effect of seasonal IPT with sulphadoxine pyrimethamine (SP) on incidence of malaria disease in area of seasonal transmission, 262 children 6 months-10 years in Kambila, Mali were randomized to receive either IPT with SP twice at eight weeks interval or no IPT during the transmission season of 2002 and were followed up for 12 months. Subjects were also followed during the subsequent transmission season in 2003 to assess possible rebound effect. Clinical malaria cases were treated with SP and followed to assess the <it>in vivo </it>response during both periods.</p> <p>Results</p> <p>The incidence rate of malaria disease per 1,000 person-months during the first 12 months was 3.2 episodes in the treatment group vs. 5.8 episodes in the control group with age-adjusted Protective Efficacy (PE) of 42.5%; [95% CI 28.6%–53.8%]. When the first 16 weeks of follow up is considered age-adjusted PE was 67.5% [95% CI 55.3% – 76.6%]. During the subsequent transmission season, the incidence of clinical malaria per 1000 persons-days was similar between the two groups (23.0 vs 21.5 episodes, age-adjusted IRR = 1.07 [95% CI, 0.90–1.27]). No significant difference was detected in <it>in vivo </it>response between the groups during both periods.</p> <p>Conclusion</p> <p>Two malaria intermittent treatments targeting the peak transmission season reduced the annual incidence rate of clinical malaria by 42.5% in an area with intense seasonal transmission. This simple strategy is likely to be one of the most effectives in reducing malaria burden in such areas.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov NCT00623155</p

Increase in EPI vaccines coverage after implementation of intermittent preventive treatment of malaria in infant with Sulfadoxine -pyrimethamine in the district of Kolokani, Mali: Results from a cluster randomized control trial

<p>Abstract</p> <p>Background</p> <p>Even though the efficacy of Intermittent Preventive Treatment in infants (IPTi) with Sulfadoxine-Pyrimethamine (SP) against clinical disease and the absence of its interaction with routine vaccines of the Expanded Immunization Programme (EPI) have been established, there are still some concerns regarding the addition of IPTi, which may increase the work burden and disrupt the routine EPI services especially in Africa where the target immunization coverage remains to be met. However IPTi may also increase the adherence of the community to EPI services and improve EPI coverage, once the benefice of strategy is perceived.</p> <p>Methods</p> <p>To assess the impact of IPTi implementation on the coverage of EPI vaccines, 22 health areas of the district of Kolokani were randomized at a 1:1 ratio to either receive IPTi-SP or to serve as a control. The EPI vaccines coverage was assessed using cross-sectional surveys at baseline in November 2006 and after one year of IPTi pilot-implementation in December 2007.</p> <p>Results</p> <p>At baseline, the proportion of children of 9-23 months who were completely vaccinated (defined as children who received BGG, 3 doses of DTP/Polio, measles and yellow fever vaccines) was 36.7% (95% CI 25.3% -48.0%). After one year of implementation of IPTi-SP using routine health services, the proportion of children completely vaccinated rose to 53.8% in the non intervention zone and 69.5% in the IPTi intervention zone (P <0.001).</p> <p>The proportion of children in the target age groups who received IPTi with each of the 3 vaccinations DTP2, DTP3 and Measles, were 89.2% (95% CI 85.9%-92.0%), 91.0% (95% CI 87.6% -93.7%) and 77.4% (95% CI 70.7%-83.2%) respectively. The corresponding figures in non intervention zone were 2.3% (95% CI 0.9% -4.7%), 2.6% (95% CI 1.0% -5.6%) and 1.7% (95% CI 0.4% - 4.9%).</p> <p>Conclusion</p> <p>This study shows that high coverage of the IPTi can be obtained when the strategy is implemented using routine health services and implementation results in a significant increase in coverage of EPI vaccines in the district of Kolokani, Mali.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00766662">NCT00766662</a></p

Space-time clustering of childhood malaria at the household level: a dynamic cohort in a Mali village

BACKGROUND: Spatial and temporal heterogeneities in the risk of malaria have led the WHO to recommend fine-scale stratification of the epidemiological situation, making it possible to set up actions and clinical or basic researches targeting high-risk zones. Before initiating such studies it is necessary to define local patterns of malaria transmission and infection (in time and in space) in order to facilitate selection of the appropriate study population and the intervention allocation. The aim of this study was to identify, spatially and temporally, high-risk zones of malaria, at the household level (resolution of 1 to 3 m). METHODS: This study took place in a Malian village with hyperendemic seasonal transmission as part of Mali-Tulane Tropical Medicine Research Center (NIAID/NIH). The study design was a dynamic cohort (22 surveys, from June 1996 to June 2001) on about 1300 children (<12 years) distributed between 173 households localized by GPS. We used the computed parasitological data to analyzed levels of Plasmodium falciparum, P. malariae and P. ovale infection and P. falciparum gametocyte carriage by means of time series and Kulldorff's scan statistic for space-time cluster detection. RESULTS: The time series analysis determined that malaria parasitemia (primarily P. falciparum) was persistently present throughout the population with the expected seasonal variability pattern and a downward temporal trend. We identified six high-risk clusters of P. falciparum infection, some of which persisted despite an overall tendency towards a decrease in risk. The first high-risk cluster of P. falciparum infection (rate ratio = 14.161) was detected from September 1996 to October 1996, in the north of the village. CONCLUSION: This study showed that, although infection proportions tended to decrease, high-risk zones persisted in the village particularly near temporal backwaters. Analysis of this heterogeneity at the household scale by GIS methods lead to target preventive actions more accurately on the high-risk zones identified. This mapping of malaria risk makes it possible to orient control programs, treating the high-risk zones identified as a matter of priority, and to improve the planning of intervention trials or research studies on malaria

Genome-wide association study of leprosy in Malawi and Mali

Leprosy is a chronic infection of the skin and peripheral nerves caused by Mycobacterium leprae. Despite recent improvements in disease control, leprosy remains an important cause of infectious disability globally. Large-scale genetic association studies in Chinese, Vietnamese and Indian populations have identified over 30 susceptibility loci for leprosy. There is a significant burden of leprosy in Africa, however it is uncertain whether the findings of published genetic association studies are generalizable to African populations. To address this, we conducted a genome-wide association study (GWAS) of leprosy in Malawian (327 cases, 436 controls) and Malian (247 cases, 368 controls) individuals. In that analysis, we replicated four risk loci previously reported in China, Vietnam and India; MHC Class I and II, LACC1 and SLC29A3. We further identified a novel leprosy susceptibility locus at 10q24 (rs2015583; combined p = 8.81 × 10-9; OR = 0.51 [95% CI 0.40 - 0.64]). Using publicly-available data we characterise regulatory activity at this locus, identifying ACTR1A as a candidate mediator of leprosy risk. This locus shows evidence of recent positive selection and demonstrates pleiotropy with established risk loci for inflammatory bowel disease and childhood-onset asthma. A shared genetic architecture for leprosy and inflammatory bowel disease has been previously described. We expand on this, strengthening the hypothesis that selection pressure driven by leprosy has shaped the evolution of autoimmune and atopic disease in modern populations. More broadly, our data highlights the importance of defining the genetic architecture of disease across genetically diverse populations, and that disease insights derived from GWAS in one population may not translate to all affected populations

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 &lt; 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

Resurgence of Ebola virus in 2021 in Guinea suggests a new paradigm for outbreaks

These authors contributed equally: Alpha K. Keita, Fara R. Koundouno, Martin Faye, Ariane Düx, Julia Hinzmann.International audienc

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Malaria and primary education in Mali: A longitudinal study in the village of Donéguébougou

ED EPS - Supplementary Materials and Associated Data on PMCentral.International audienceThis article assesses the role of malaria and certain social determinants on primary education, especially on educational achievement in Donéguébougou, a small village in a malaria-endemic area near Bamako, Mali. Field data was collected by the authors between November 2007 and June 2008 on 227 schoolchildren living in Donéguébougou. Various malaria indicators and econometric models were used to explain the variation in cognitive abilities, teachers' evaluation scores, school progression and absences. Malaria is the primary cause of school absences. Fixed-effects estimates showed that asymptomatic malaria and the presence of falciparum malaria parasites had a direct correlation with educational achievement and cognitive performance. The evidence suggests that the correlation is causal

Malaria and primary education in Mali: A longitudinal study in the village of Donéguébougou

This article assesses the role of malaria and certain social determinants on primary education, especially on educational achievement in Donéguébougou, a small village in a malaria-endemic area near Bamako, Mali. Field data was collected by the authors between November 2007 and June 2008 on 227 schoolchildren living in Donéguébougou. Various malaria indicators and econometric models were used to explain the variation in cognitive abilities, teachers' evaluation scores, school progression and absences. Malaria is the primary cause of school absences. Fixed-effects estimates showed that asymptomatic malaria and the presence of falciparum malaria parasites had a direct correlation with educational achievement and cognitive performance. The evidence suggests that the correlation is causal.Malaria Human capital Education Mali Children