Explore the vast range of titles available.

In this randomized, placebo-controlled trial, azithromycin was assessed as an adjuvant agent for malaria prevention in children in Burkina Faso and Mali. No survival or antimalarial benefit associated with azithromycin was observed.

Seasonal malaria chemoprevention (SMC) has shown high protective efficacy against clinical malaria and severe malaria in a series of clinical trials. We evaluated the effectiveness of SMC treatments against clinical malaria when delivered at scale through national malaria control programmes in 2015 and 2016. Case-control studies were carried out in Mali and The Gambia in 2015, and in Burkina Faso, Chad, Mali, Nigeria, and The Gambia in 2016. Children aged 3-59 months presenting at selected health facilities with microscopically confirmed clinical malaria were recruited as cases. Two controls per case were recruited concurrently (on or shortly after the day the case was detected) from the neighbourhood in which the case lived. The primary exposure was the time since the most recent course of SMC treatment, determined from SMC recipient cards, caregiver recall, and administrative records. Conditional logistic regression was used to estimate the odds ratio (OR) associated with receipt of SMC within the previous 28 days, and SMC 29 to 42 days ago, compared with no SMC in the past 42 days. These ORs, which are equivalent to incidence rate ratios, were used to calculate the percentage reduction in clinical malaria incidence in the corresponding time periods. Results from individual countries were pooled in a random-effects meta-analysis. In total, 2,126 cases and 4,252 controls were included in the analysis. Across the 7 studies, the mean age ranged from 1.7 to 2.4 years and from 2.1 to 2.8 years among controls and cases, respectively; 42.2%-50.9% and 38.9%-46.9% of controls and cases, respectively, were male. In all 7 individual case-control studies, a high degree of personal protection from SMC against clinical malaria was observed, ranging from 73% in Mali in 2016 to 98% in Mali in 2015. The overall OR for SMC within 28 days was 0.12 (95% CI: 0.06, 0.21; p < 0.001), indicating a protective effectiveness of 88% (95% CI: 79%, 94%). Effectiveness against clinical malaria for SMC 29-42 days ago was 61% (95% CI: 47%, 72%). Similar results were obtained when the analysis was restricted to cases with parasite density in excess of 5,000 parasites per microlitre: Protective effectiveness 90% (95% CI: 79%, 96%; P<0.001), and 59% (95% CI: 34%, 74%; P<0.001) for SMC 0-28 days and 29-42 days ago, respectively. Potential limitations include the possibility of residual confounding due to an association between exposure to malaria and access to SMC, or differences in access to SMC between patients attending a clinic and community controls; however, neighbourhood matching of cases and controls, and covariate adjustment, attempted to control for these aspects, and the observed decline in protection over time, consistent with expected trends, argues against a major bias from these sources. SMC administered as part of routine national malaria control activities provided a very high level of personal protection against clinical malaria over 28 days post-treatment, similar to the efficacy observed in clinical trials. The case-control design used in this study can be used at intervals to ensure SMC treatments remain effective.

Malaria is the leading cause of morbidity and mortality in Mali. Between 2017 and 2020, the number of cases increased in the country, with 2,884,827 confirmed cases and 1454 reported deaths in 2020. We performed a malaria risk stratification at the health district level in Mali with a view to proposing targeted control interventions. Data on confirmed malaria cases were obtained from the District Health Information Software 2, data on malaria prevalence and mortality in children aged 6–59 months from the 2018 Demographic and Health Survey, entomological data from Malian research institutions working on malaria in the sentinel sites of the National Malaria Control Program (NMCP), and environmental data from the National Aeronautics and Space Administration. A stratification of malaria risk was performed. Targeted malaria control interventions were selected based on spatial heterogeneity of malaria incidence, malaria prevalence in children, vector resistance distribution, health facility usage, child mortality, and seasonality of transmission. These interventions were discussed with the NMCP and the different funding partners. In 2017–2019, median incidence across the 75 health districts was 129.34 cases per 1000 person-years (standard deviation = 86.48). Risk stratification identified 12 health districts in very low transmission areas, 19 in low transmission areas, 20 in moderate transmission areas, and 24 in high transmission areas. Low health facility usage and increased vector resistance were observed in high transmission areas. Eight intervention combinations were selected for implementation. Our work provides an updated risk stratification using advanced statistical methods to inform the targeting of malaria control interventions in Mali. This stratification can serve as a template for continuous malaria risk stratifications in Mali and other countries.

In Mali, some children were treated by community health workers, using a rapid diagnostic test (RDT) to confirm Plasmodium falciparum parasitaemia. The following passively detected outcomes were included in this study: 1) incidence of malaria hospital admissions or deaths from malaria (as a combined outcome), defined as hospital admission for malaria combined with a positive blood slide or rapid diagnostic test, or deaths for which malaria was listed as the primary diagnosis; and 2) uncomplicated clinical malaria episodes, defined as history of fever or measured axillary temperature ≥37.5 °C combined with a positive RDT. At the end of each rainy season, the prevalence of P. falciparum infection was determined amongst randomly selected study children at cross-sectional surveys (target sample size of 2,000 per country, 1,000 per randomisation group in each country). The presence of molecular markers of resistance of P. falciparum to SP and AQ was determined amongst all study children who carried P. falciparum infection at the end-of-season surveys and from 50 school-age children with P. falciparum infection at the same time point.

Background Seasonal malaria chemoprevention is widely implemented in Sahel and sub-Sahel countries in Africa. Few studies have assessed the impact of the SMC on hospital admission and death when it is implemented in the health system. This retrospective study assessed the impact of seasonal malaria chemoprevention (SMC) on hospitalizations and deaths of children under 5 years of age during the second year of implementation of SMC in the health district of Ouelessebougou in Mali. Methods In February 2017, a survey was conducted to assess hospital admissions and deaths in children under 5 years of age in two health sub-districts where SMC was implemented in 2015 and two health sub-districts where SMC was not implemented. The survey reviewed deaths and hospitalizations of children under 5, in the four health sub-districts. The crude and specific incidence rates of hospitalizations and deaths were determined in both groups and expressed per 1000 children per year. A negative binomial regression model and a Cox model were used to estimate the relative risks of hospitalization and death after adjusting for confounders. The R software was used for data analysis. Results A total of 6638 children under 5 years of age were surveyed, 2759 children in the SMC intervention areas and 3879 children in the control areas. All causes mortality rate per 1000 person-years was 8.29 in the control areas compared to 3.63 in the intervention areas; age and gender adjusted mortality rate ratio 0.44 (95% CI 0.22–0.91), p = 0.027. The incidence rate of all causes hospital admissions was 19.60 per 1000 person-years in the intervention group compared to 33.45 per 1000 person-years in the control group, giving an incidence rate ratio (IRR) adjusted for age and gender of 0.61 (95% CI 0.44–0.84), p = 0.003. Conclusion The implementation of SMC was associated with a substantial reduction in hospital admissions and all-cause mortality. Trial registration ClinicalTrials.gov NCT02646410.

Background A recent trial of 5920 children in Burkina Faso and Mali showed that the combination of seasonal vaccination with the RTS,S/AS01 E malaria vaccine (primary series and two seasonal boosters) and seasonal malaria chemoprevention (four monthly cycles per year) was markedly more effective than either intervention given alone in preventing clinical malaria, severe malaria, and deaths from malaria. Methods In order to help optimise the timing of these two interventions, trial data were reanalysed to estimate the duration of protection against clinical malaria provided by RTS,S/AS01 E when deployed seasonally, by comparing the group who received the combination of SMC and RTS,S/AS01 E with the group who received SMC alone. The duration of protection from SMC was also estimated comparing the combined intervention group with the group who received RTS,S/AS01 E alone. Three methods were used: Piecewise Cox regression, Flexible parametric survival models and Smoothed Schoenfeld residuals from Cox models, stratifying on the study area and using robust standard errors to control for within-child clustering of multiple episodes. Results The overall protective efficacy from RTS,S/AS01 E over 6 months was at least 60% following the primary series and the two seasonal booster doses and remained at a high level over the full malaria transmission season. Beyond 6 months, protective efficacy appeared to wane more rapidly, but the uncertainty around the estimates increases due to the lower number of cases during this period (coinciding with the onset of the dry season). Protection from SMC exceeded 90% in the first 2–3 weeks post-administration after several cycles, but was not 100%, even immediately post-administration. Efficacy begins to decline from approximately day 21 and then declines more sharply after day 28, indicating the importance of preserving the delivery interval for SMC cycles at a maximum of four weeks. Conclusions The efficacy of both interventions was highest immediately post-administration. Understanding differences between these interventions in their peak efficacy and how rapidly efficacy declines over time will help to optimise the scheduling of SMC, malaria vaccination and the combination in areas of seasonal transmission with differing epidemiology, and using different vaccine delivery systems. Trial registration The RTS,S-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT03143218

WHO and its partners have adopted alternative control interventions since the failure to eradicate malaria worldwide in the 1960s and 1970s. The aim of these interventions has been to redesign the control interventions to make them more effective and more efficient. The purpose of this study is to assess the population impact of control interventions implemented at the community health area level. The analysis used data from the health information system on malaria cases and interventions (distribution of long-lasting insecticide-treated nets (LLINs), seasonal malaria chemoprevention (SMC), access to rapid diagnostic tests (RDT), intermittent preventive treatment for pregnant women (IPTp)) collected in the Kati health district from 2017 to 2020. And the contextual parameters (temperature, normal difference vegetation index (NDVI) and rainfall) were obtained by remote sensing. A generalized additive model was used to assess the impact of malaria control interventions on malaria cases as a function of meteorological factors. The incidence of malaria varies from year to year and from health area to health area, as do meteorological factors in the study area. The distribution of long-lasting insecticide-treated nets, chemoprevention of seasonal malaria in children and access to rapid diagnostic tests for malaria were found to have a significant impact on the incidence of malaria in the population. Seasonal malaria chemoprevention was effective in reducing the incidence of malaria, while distribution of long-lasting insecticide-treated nets and access to rapid diagnostic tests increased with the number of malaria cases, reflecting efforts to distribute and use bed nets and to diagnose malaria cases among the population in the study area. The study showed the impact of SMC on reducing malaria cases in the population and the significant efforts in LLIN distribution and malaria case diagnosis. To further reduce the burden of malaria, sustained efforts and new interventions are needed, including improving access to rapid diagnosis and treatment in communities by developing community health workers and locally tailored mass drug administration.

Background Seasonal malaria chemoprevention (SMC) is a new strategy recommended by WHO in areas of highly seasonal transmission in March 2012. Although randomized controlled trials (RCTs) have shown SMC to be highly effective, evidence and experience from routine implementation of SMC are limited. Methods A non-randomized pragmatic trial with pre-post design was used, with one intervention district (Kita), where four rounds of SMC with sulfadoxine + amodiaquine (SP + AQ) took place in August–November 2014, and one comparison district (Bafoulabe). The primary aims were to evaluate SMC coverage and reductions in prevalence of malaria and anaemia when SMC is delivered through routine programmes using existing community health workers. Children aged 3–59 months from 15 selected localities per district, sampled with probability proportional to size, were surveyed and blood samples collected for malaria blood smears, haemoglobin (Hb) measurement, and molecular markers of drug resistance in two cross-sectional surveys, one before SMC (July 2014) and one after SMC (December 2014). Difference-in-differences regression models were used to assess and compare changes in malaria and anaemia in the intervention and comparison districts. Adherence and tolerability of SMC were assessed by cross-sectional surveys 4–7 days after each SMC round. Coverage of SMC was assessed in the post-SMC survey. Results During round 1, 84% of targeted children received at least the first SMC dose, but coverage declined to 67% by round 4. Across the four treatment rounds, 54% of children received four complete SMC courses. Prevalence of parasitaemia was similar in intervention and comparison districts prior to SMC (23.4 vs 29.5%, p = 0.34) as was the prevalence of malaria illness (2.4 vs 1.9%, p = 0.75). After SMC, parasitaemia prevalence fell to 18% in the intervention district and increased to 46% in the comparison district [difference-in-differences (DD) OR = 0.35; 95% CI 0.20–0.60]. Prevalence of malaria illness fell to a greater degree in the intervention district versus the comparison district (DD OR = 0.20; 95% CI 0.04–0.94) and the same for moderate anaemia (Hb < 8 g/dL) (DD OR = 0.26, 95% CI 0.11–0.65). The frequency of the quintuple mutation (dhfr N51I, C59R and S108N + dhps A437G and K540E) remained low (5%) before and after intervention in both districts. Conclusions Routine implementation of SMC in Mali substantially reduced malaria and anaemia, with reductions of similar magnitude to those seen in previous RCTs. Improving coverage could further strengthen SMC impact. Trial registration clinical trial registration number NCT02894294

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

ProC6C is a multi-stage malaria vaccine which includes Circumsporozoite Protein (PfCSP), Pfs48/45 and Pfs230 sequences, designed to elicit functional antibodies that prevent sporozoite invasion of human hepatocytes (PfCSP) and parasite development in mosquitoes (Pfs48/45 and Pfs230). ProC6C formulated on Alhydrogel was evaluated in combination with Matrix-M in a Phase 1 trial in Burkina Faso. The PfCSP antibody responses were assessed for magnitude, specificity, avidity and functionality. These results compliment the prior reported safety and tolerability of ProC6C as well as the transmission reducing activity of ProC6C. The PfCSP response of ProC6C in Burkinabes in the Phase 1 trial (PACTR202201848463189) was profiled through the three vaccine administrations of 100 µg protein on Alhydrogel alone (AlOH) or combined with 50 µg Matrix-M™ adjuvant (AlOH/Matrix-M). Serology was completed against full-length PfCSP and major/minor repeat peptides using antibody equivalence to PfCSP monoclonal antibodies (mAb 311, mAb 317 and mAb L9). Comparison of the ProC6C responses were made to those that received RTS,S/AS01 in a study conducted in Thailand. Bio-Layer Interferometry was further used to determine antibody avidity. The human IgG was subsequently purified, pooled, and evaluated in a mouse sporozoite challenge model to determine functionality. A single administration of ProC6C-AlOH/Matrix-M seroconverted 19 of 20 volunteers against PfCSP and significantly enhanced antibody titers to major and minor repeats (and present through D180). At D70, ProC6C-AlOH/Matrix-M PfCSP antibodies were found to be similar to responder pools generated from Thai adults receiving RTS,S/AS01. Additionally, ProC6C antibodies were found to be competitive to established PfCSP antibodies such as mAb 317 and mAb L9. The purified and pooled IgG from human volunteers, used in a passive transfer mouse sporozoite challenge model, showed a median of 50% inhibition (P=0.0058). ProC6C PfCSP antibodies were functional in this assessment and consistent with inhibition seen by other Circumsporozoite vaccines in this model. This analysis supports continued investigation of the antibody responses elicited by the ProC6C multi-stage malaria vaccine. This Phase 1 clinical trial demonstrated the short PfCSP sequence included in ProC6C can induce significant PfCSP antibodies in humans, which importantly were determined to be functional.