We surveyed an Anopheles gambiae population in a West African malaria transmission zone for naturally occurring genetic loci that control mosquito infection with the human malaria parasite, Plasmodium falciparum. The strongest Plasmodium resistance loci cluster in a small region of chromosome 2L and each locus explains at least 89% of parasite-free mosquitoes in independent pedigrees. Together, the clustered loci form a genomic Plasmodium-resistance island that explains most of the genetic variation for malaria parasite infection of mosquitoes in nature. Among the candidate genes in this chromosome region, RNA interference knockdown assays confirm a role in Plasmodium resistance for Anopheles Plasmodium-responsive leucine-rich repeat 1 (APL1), encoding a leucine-rich repeat protein that is similar to molecules involved in natural pathogen resistance mechanisms in plants and mammals.

A double blind, randomized, controlled Phase 2 clinical trial was conducted to assess the safety, immunogenicity, and biologic impact of the vaccine candidate Apical Membrane Antigen 1-Combination 1 (AMA1-C1), adjuvanted with Alhydrogel ® . Participants were healthy children 2-3 years old living in or near the village of Bancoumana, Mali. A total of 300 children received either the study vaccine or the comparator. No impact of vaccination was seen on the primary endpoint, the frequency of parasitemia measured as episodes >3000 per μL per day at risk. There was a negative impact of vaccination on the hemoglobin level during clinical malaria, and mean incidence of hemoglobin <8.5 g/dL, in the direction of lower hemoglobin in the children who received AMA1-C1, although these differences were not significant after correction for multiple tests. These differences were not seen in the second year of transmission.

Background: Spatial and temporal heterogeneities in the risk of malaria have led the WHO to recommend finescale 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).

BackgroundThe objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria.Methodology/Principal FindingsA phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18–55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 µg/AS02A 0.25 mL or FMP2.1 50 µg/AS02A 0.5 mL) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively.Conclusion/SignificanceThe FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.Trial RegistrationClinicalTrials.gov NCT00308061

BackgroundCoverage of malaria in pregnancy interventions in sub-Saharan Africa is suboptimal. We undertook a systematic examination of the operational, socio-economic and cultural constraints to pregnant women’s access to intermittent preventive treatment (IPTp), long-lasting insecticide-treated nets (LLINs) and case management in Kenya and Mali to provide empirical evidence for strategies to improve coverage.MethodsFocus group discussions (FGDs) were held as part of a programme of research to explore the delivery, access and use of interventions to control malaria in pregnancy. FGDs were held with four sub-groups: non-pregnant women of child bearing age (aged 15–49 years), pregnant women or mothers of children aged <1 year, adolescent women, and men. Content analysis was used to develop themes and sub-themes from the data.ResultsWomen and men’s perceptions of the benefits of antenatal care were generally positive; motivation among women consisted of maintaining a healthy pregnancy, disease prevention in mother and foetus, checking the position of the baby in preparation for delivery, and ensuring admission to a facility in case of complications. Barriers to accessing care related to the quality of the health provider-client interaction, perceived health provider skills and malpractice, drug availability, and cost of services. Pregnant women perceived themselves and their babies at particular risk from malaria, and valued diagnosis and treatment from a health professional, but cost of treatment at health facilities drove women to use herbal remedies or drugs bought from shops. Women lacked information on the safety, efficacy and side effects of antimalarial use in pregnancy.ConclusionWomen in these settings appreciated the benefits of antenatal care and yet health services in both countries are losing women to follow-up due to factors that can be improved with greater political will. Antenatal services need to be patient-centred, free-of-charge or highly affordable and accountable to the women they serve.

IntroductionDelivery of intermittent preventive treatment with sulphadoxine-pyrimethamine to pregnant women (IPTp-SP) through antenatal clinic (ANC) in Mali is low, and whilst ANC delivery of insecticide treated nets (ITNs) is higher, coverage is still below national and international targets. The aim of this study was to explain quantitative data from a related study which identified ineffective processes in the delivery of these interventions in one district in Mali.MethodsIn-depth interviews were conducted with health workers at the national, regional, district and health facility levels on their perceptions of reasons for the ineffective processes identified in the quantitative study, and their reported practices. Themes were coded for each ineffective process, and within these a health systems lens was used. Content analysis was used for emergent themes within this framework. MindMaps were used to display the findings.ResultsIntervention specific factors for the ineffective delivery of IPTp-SP included misunderstanding of the upper limit of the gestational age at which SP could be given and side effects of SP. Incorrect practices had been recommended in training and supervision of health workers. Pregnant women who were ill on attendance at ANC were not consistently managed across health facilities. The most common reason for not offering women an ITN on their first ANC visit was if they were from outside the health facility catchment area. Broader health systems issues influencing the effectiveness of delivery of each of these interventions were also identified.ConclusionIn this setting, intervention-specific factors resulted in the ineffective delivery of IPTp-SP. These relate to complex policy guidelines, lack of guidance on how to implement the guidelines, and the institutionalising of practices that undermine the national guidelines. Interventions may be implemented and show real gains in the shorter-term whilst waiting for broader health systems issues to be addressed.

IntroductionThe objectives of the study were to evaluate the health system effectiveness of ANC for the delivery of a dose of IPTp and an ITN to women attending ANC during eligible gestation, and to identify the predictors of systems effectiveness.MethodsA cross sectional study was undertaken in 10 health facilities including structured non-participant observations of the ANC process for 780 pregnant women followed by exit interviews. The proportion of pregnant women receiving a dose of IPTp-SP and an ITN was assessed. Predictors of each ineffective intermediate process were identified using multivariable logistic regression.ResultsOverall, 0% and 24.5% of pregnant women of eligible gestation on the first visit to ANC received a dose of IPTp-SP by DOT at the district and community levels respectively. Ineffective intermediate processes were ‘given IPTp-SP at the ANC’ 63.9% and 74.0% (95% CI 62.0, 83.3), and ‘given IPTp-SP by DOT’ 0% and 34.3% (95% CI 10.5, 69.8), at district and community levels, respectively. Delivery of ITNs was effective where they were in stock; however stock-outs were a problem. Predictors of receiving IPTp-SP at the district level were 4 to 6 months gestation, not reporting symptoms of malaria at ANC visit and the amount of money spent during the visit. At the community level, the predictors were 4 to 6 months gestation, maternal education below primary level, routine ANC visit (not for an illness), palpation of the abdomen, and expenditure of money in ANC.ConclusionIn Segou District, the delivery of IPTp-SP was ineffective; whilst ITN delivery was effective if ITNs were in stock. Predictors of receiving IPTp-SP at the district and community levels included gestational age, the amount of expenditure during the ANC visit and no illness.

Background: Seasonal malaria chemoprevention (SMC) is a new strategy to prevent malaria in children under 5 years old. It has been recommended by the World Health Organization since 2012 in malaria-endemic areas with seasonal transmission. This study aimed to assess the changes in malaria indicators through two consecutive years of SMC routine implementation in children under 5 years old in Dangassa, where malaria is endemic with a long and high transmission season. Methods: From 2012 to 2016, a cohort study was conducted in Dangassa village. The study team based in the village followed all malaria clinical cases in children under 5 years old at the community health centre. During the study, SMC was routinely implemented in collaboration with the National Malaria Control Programme. The Cox regression model was used in order to compare malaria risk during the study. Results: The Cox regression model showed a significant reduction in malaria clinical incidence, both in 2015 (HR = 0.27 (0.18-0.40), 95% CI) and in 2016 (HR = 0.23 (0.15-0.35), 95% CI) of SMC implementation compared to October 2013. Gametocyte and fever prevalence was lower between September and October during SMC implementation (2015 and 2016) compared to the same period before SMC implementation (2013-2014). A slight increase of malaria incidence was observed in December at the end of SMC implementation. Conclusion: SMC has significantly reduced both malaria incidence and gametocyte prevalence and improved haemoglobin levels in children under 5 years old after 2 years of routine implementation.