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Many African countries have reported declines in malaria incidence, attributed to the implementation of control strategies. In Mali, artemisinin-based combination therapy (ACT) was introduced in 2004, and long-lasting insecticide-treated nets (LLINs) have been partially distributed free of charge since 2007. In the Malian town of Bandiagara, a study conducted from 2009 to 2013 showed a stable incidence of malaria compared with 1999, despite the implementation of ACTs and LLINs. Since 2016, seasonal malaria chemoprevention has been scaled up across the country. In addition to these strategies, the population of Bandiagara benefited from indoor residual spray implementation in 2017 and 2018 and continued universal bed net coverage. This study aimed to measure the incidence of malaria in Bandiagara, given this recent scaling up of control strategies. A cohort of 300 children aged 6 months to 15 years was followed up from October 2017 to December 2018. We performed monthly cross-sectional surveys to measure anemia and the prevalence of malaria infection by microscopy. The overall incidence of symptomatic malaria was 0.5 episodes/person-year. Malaria incidence in children up to 5 years old significantly declined since 2012 and since 1999 (incidence rate ratio estimates: 6.7 [95% CI: 4.2–11.4] and 13.5 [95% CI: 8.4–22.7]), respectively. The average prevalence of malaria parasitemia was 6.7%. Malaria incidence was higher in children older than 5 years than in those younger than 5 years, highlighting the need to extend malaria control efforts to these older children.

var genes encode Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) antigens. These highly diverse antigens are displayed on the surface of infected erythrocytes and play a critical role in immune evasion and sequestration of infected erythrocytes. Studies of var expression using non-leukocyte-depleted blood are challenging because of the predominance of host genetic material and lack of conserved var segments. Our goal was to enrich for parasite RNA, allowing de novo assembly of var genes and detection of expressed novel variants. We used two overall approaches: (i) enriching for total mRNA in the sequencing library preparations and (ii) enriching for parasite RNA with a custom capture array based on Roche’s SeqCap EZ enrichment system. The capture array was designed with probes based on the whole 3D7 reference genome and an additional >4,000 full-length var gene sequences from other P. falciparum strains. We tested each method on RNA samples from Malian children with severe or uncomplicated malaria infections. All reads mapping to the human genome were removed, the remaining reads were assembled de novo into transcripts, and from these, var-like transcripts were identified and annotated. The capture array produced the longest maximum length and largest numbers of var gene transcripts in each sample, particularly in samples with low parasitemia. Identifying the most-expressed var gene sequences in whole-blood clinical samples without the need for extensive processing or generating sample-specific reference genome data is critical for understanding the role of PfEMP1s in malaria pathogenesis. IMPORTANCE Malaria parasites display antigens on the surface of infected red blood cells in the human host that facilitate attachment to blood vessels, contributing to the severity of infection. These antigens are highly variable, allowing the parasite to evade the immune system. Identifying these expressed antigens is critical to understanding the development of severe malarial disease. However, clinical samples contain limited amounts of parasite genetic material, a challenge for sequencing efforts further compounded by the extreme diversity of the parasite surface antigens. We present a method that enriches for these antigen sequences in clinical samples using a custom capture array, requiring minimal processing in the field. While our results are focused on the malaria parasite Plasmodium falciparum, this approach has broad applicability to other highly diverse antigens from other parasites and pathogens such as those that cause giardiasis and leishmaniasis.

Following Plasmodium falciparum infection, individuals can remain asymptomatic, present with mild fever in uncomplicated malaria cases, or show one or more severe malaria symptoms. Several studies have investigated associations between parasite transcription and clinical severity, but no broad conclusions have yet been drawn. Here, we apply a series of bioinformatic approaches based on P. falciparum’s tightly regulated transcriptional pattern during its ~48-hour intraerythrocytic developmental cycle (IDC) to publicly available transcriptomes of parasites obtained from malaria cases of differing clinical severity across multiple studies. Our analysis shows that within each IDC, the circulation time of infected erythrocytes without sequestering to endothelial cells decreases with increasing parasitaemia or disease severity. Accordingly, we find that the size of circulating infected erythrocytes is inversely related to parasite density and disease severity. We propose that enhanced adhesiveness of infected erythrocytes leads to a rapid increase in parasite burden, promoting higher parasitaemia and increased disease severity., To understand malaria symptoms, several studies investigate association between parasite’s transcriptome and disease severity. Here, Thomson-Luque et al. reanalyze available transcriptomic data of P. falciparum and find that longer circulation of infected erythrocytes without sequestering to endothelial cells associates with decreasing parasitaemia and less severe disease.

In Mali, since 2007, artemether-lumefantrine has been the first choice against uncomplicated malaria. Despite its effectiveness, a rapid selection of markers of resistance to partner drugs has been documented. This work evaluated the treatment according to the World Health Organization&rsquo, s standard 28-day treatment method. The primary endpoint was the clinical and parasitological response corrected by a polymerase chain reaction. It was more than 99.9 percent, the proportion of patients with anemia significantly decrease compared to baseline (p &lt, 0.001), and no serious events were recorded. Plasmodium falciparum remains sensitive to artemether-lumefantrine in Mali.

In Mali, since 2007, artemether-lumefantrine has been the first choice against uncomplicated malaria. Despite its effectiveness, a rapid selection of markers of resistance to partner drugs has been documented. This work evaluated the treatment according to the World Health Organization’s standard 28-day treatment method. The primary endpoint was the clinical and parasitological response corrected by a polymerase chain reaction. It was more than 99.9 percent, the proportion of patients with anemia significantly decrease compared to baseline (p < 0.001), and no serious events were recorded. Plasmodium falciparum remains sensitive to artemether-lumefantrine in Mali.

BackgroundEvaluation of local transmission epidemiology to characterize malaria risk is essential for planning malaria control and elimination programmes. The use of geographical information systems (GIS) has been a major asset to this approach. This study aimed to characterize the local spatio-temporal pattern of malaria infection and clinical disease after implementation of Seasonal Malaria Chemoprevention (SMC) and Indoor Residual Spraying (IRS) in Bandiagara, a Malian town.MethodsFrom October 2017 to December 2018, an active and passive surveillance system was established in a cohort study of three hundred children aged from 6 months to 15 years old. Weekly time-series of clinical malaria and monthly time-series of asymptomatic Plasmodium carriage and rainfall were plotted. Numbers of clinical malaria episodes and asymptomatic parasite carriers were mapped using Quantum Geographic Information System (QGIS). Landscape features of Bandiagara were obtained from Google earth. Clusters of high or low risk were identified under SaTScan® software using a Bernoulli model. ResultsFrom October 2017 to December 2018, 167 clinical malaria cases were recorded, mostly from July to December, while asymptomatic parasite carriage was observed during the entire study period. Three clusters of clinical episodes were found. All were hotspots. They were located in the north-east, south and west. No low risk cluster was identified. Three significant high-risk clusters of asymptomatic parasite carriage were identified in the south, north-east and north. These clusters were located near standing water. ConclusionThis study confirms the seasonality of clinical malaria in Bandiagara. The continued presence of asymptomatic parasite carriers maintains malaria transmission. To advance malaria elimination, control strategies must also target hotspots of asymptomatic parasite carriage. There was a spatial heterogeneity of clinical and asymptomatic malaria. Despite the implementation of additional preventives strategies, the locations of high-risk clusters were stable.

BackgroundDeclines in malaria incidence attributed to the implementation of control strategies have been reported in many African countries. The declines are often accompanied by a shift in clinical burden to older children. In Mali, artemisinin-based combination therapy (ACT) was introduced in 2004, and Long-lasting insecticide-treated nets (LLINs) have been partially distributed free of charge since 2007. In Bandiagara, a study conducted from 2009 to 2013 showed a stable incidence of malaria compared to 1999 despite the use of ACTs and LLINs. Since 2016, seasonal malaria chemoprevention (SMC) has been scaled up across the country. In addition to these strategies, the population of Bandiagara benefited the universal bed net coverage and indoor residual spray (IRS) implementation in 2017 and 2018.This study aimed to measure the incidence of malaria in the context of recent scaling-up of control strategies.MethodsA cohort of 300 children aged 6 months to 15 years was followed from October 2017 to December 2018 in Mali. Monthly cross-sectional surveys were done to measure the prevalence of malaria infection by microscopy and anaemia. The study outcomes included the monthly prevalence of malaria infection and the incidence of symptomatic malaria.ResultsThe incidence of symptomatic malaria was 0.5 episodes/person-year. The average prevalence of malaria parasitaemia was 6.7%. The incidence was higher in the oldest age group than the youngest one (0.6 episodes/person-year in children above 10 years vs 0.29 in 6 months to 5 years age group).ConclusionsThis study showed a reduction of malaria incidence compared to 1999 and 2009-2013. An age shift in the susceptibility to malaria was also observed; older children experienced more clinical malaria than younger ones. These findings suggest to extend malaria control efforts to older children.

International audience; These authors contributed equally to this work. Abstract. In areas of seasonal malaria transmission, the incidence rate of malaria infection is presumed to be near zero at the end of the dry season. Asymptomatic individuals may constitute a major parasite reservoir during this time. We conducted a longitudinal analysis of the spatio-temporal distribution of clinical malaria and asymptomatic parasitemia over time in a Malian town to highlight these malaria transmission dynamics. For a cohort of 300 rural children followed over 2009–2014, periodicity and phase shift between malaria and rainfall were determined by spectral analysis. Spatial risk clusters of clinical episodes or carriage were identified. A nested-case-control study was conducted to assess the parasite carriage factors. Malaria infection persisted over the entire year with seasonal peaks. High transmission periods began 2–3 months after the rains began. A cluster with a low risk of clinical malaria in the town center persisted in high and low transmission periods. Throughout 2009–2014, cluster locations did not vary from year to year. Asymptomatic and gametocyte carriage were persistent, even during low transmission periods. For high transmission periods, the ratio of asymptomatic to clinical cases was approximately 0.5, but was five times higher during low transmission periods. Clinical episodes at previous high transmission periods were a protective factor for asymptomatic carriage, but carrying parasites without symptoms at a previous high transmission period was a risk factor for asymptomatic carriage. Stable malaria transmission was associated with sustained asymptomatic carriage during dry seasons. Control strategies should target persistent low-level parasitemia clusters to interrupt transmission.

BackgroundMalaria remains a leading cause of child mortality in sub-Saharan Africa. Severe malaria is the main pathway to death caused by malaria. A study of factors associated with protection against severe malaria is best achieved using a case-control design. However, these studies are affected by the quality and appropriateness of the choice of controls that may introduce important bias in study design and definitively alter the conclusions from the studies. It is of paramount importance that the presence or absence of an episode of severe malaria in the history of the controls is ascertained. In settings with reliable medical data this is easily tracked back from hospital records. In settings like Bandiagara, with weak health care systems, a dedicated approach is needed to track history of severe malaria. We used an adapted verbal autopsy questionnaire to identify presence of cerebral malaria in the history of controls in a case-control study of severe malaria in Bandiagara.We have assessed the sensitivity, specificity and predictive positive and negative values of the questionnaire.MethodsFrom January through August 2018 we enrolled 450 children with or without known confirmed cerebral malaria selected at health care centers in Bandiagara and Bamako, with archived medical records. Parents of enrolled children were identified, located and interviewed using the adapted verbal autopsy questionnaire. Interviewers were not aware of children’s diagnosis. We compared the diagnosis derived from the verbal autopsy questionnaire to the confirmed biological diagnosis from the medical records.ResultsWe will present full results on the sensitivity, specificity, the predictive positive and negative values of the verbal questionnaire, and the Kappa coefficient of agreement.ConclusionA good verbal questionnaire will enhance the quality of the choice of controls in case-control studies of severe malaria and overall will improve the quality and relevance of inferences from such studies.

Background The recent decline in malaria incidence in many African countries has been attributed to the provision of prompt and effective anti-malarial treatment using artemisinin-based combination therapy (ACT) and to the widespread distribution of long-lasting, insecticide-treated bed nets (LLINs). At a malaria vaccine-testing site in Bandiagara, Mali, ACT was introduced in 2004, and LLINs have been distributed free of charge since 2007 to infants after they complete the Expanded Programme of Immunization (EPI) schedule and to pregnant women receiving antenatal care. These strategies may have an impact on malaria incidence. Methods To document malaria incidence, a cohort of 400 children aged 0 to 14 years was followed for three to four years up to July 2013. Monthly cross-sectional surveys were done to measure the prevalence of malaria infection and anaemia. Clinical disease was measured both actively and passively through continuous availability of primary medical care. Measured outcomes included asymptomatic Plasmodium infection, anaemia and clinical malaria episodes. Results The incidence rate of clinical malaria varied significantly from June 2009 to July 2013 without a clear downward trend. A sharp seasonality in malaria illness incidence was observed with higher clinical malaria incidence rates during the rainy season. Parasite and anaemia point prevalence also showed seasonal variation with much higher prevalence rates during rainy seasons compared to dry seasons. Conclusions Despite the scaling up of malaria prevention and treatment, including the widespread use of bed nets, better diagnosis and wider availability of ACT, malaria incidence did not decrease in Bandiagara during the study period.