The Role of Antibodies to <i>Plasmodium falciparum</i> Merozoite Antigens in the Resistance of Young Infants to Febrile Malaria and Their Place as a Biomarker in the Detection of Malaria Transmission Hotspots

Over the last 15 years the malaria burden has globally declined, but not evenly across endemic areas. In areas with substantial decline, elimination became realistic. However, malaria elimination has to, in a cost-effective way, overcome problems such as increasing drug and insecticide resistance and the increasing heterogeneity in transmission as the transmission intensity declines. Vaccines are proven cost-effective tools in infectious disease control and substantial progress was made with the RTS, S vaccine. However, vaccine development is hampered by the lack of reliable immune correlates of protection. We have analysed antibody responses in relation to the incidence of febrile malaria in young children, with the specific objective of investigating their contribution to the apparent resistance of young infants to febrile malaria. We have also analysed the dynamics of antibodies in relation to previously established protective thresholds. We found that the antibody responses to 6 different falciparum antigens were not associated with protection against febrile malaria in young children and that their levels were consistently below the protective thresholds. Furthermore, we found that antibody titres were often actually associated with increasing risk of febrile malaria. A likely explanation is that the antibodies were markers of exposure and hence associated with higher risk. We therefore analysed geo-spatial data on malaria risk to identify hotspots of clinical malaria and their association with hotspots of serological responses to malaria antigens. We found that 1) antibody responses correlated well with asymptomatic parasitaemia detected by polymerase chain reaction, and 2) there was substantial overlapping between the hotspots detected using these markers. Our data suggest that other mechanisms are responsible for the apparent resistance of infants to febrile malaria. Moreover, our data suggest that serology or polymerase chain reaction results may be used as markers for the detection of hotspots when the transmission declines to very low levels

Cord blood IgG and the risk of severe Plasmodium falciparum malaria in the first year of life

Young infants are less susceptible to severe episodes of malaria but the targets and mechanisms of protection are not clear. Cord blood antibodies may play an important role in mediating protection but many studies have examined their association with the outcome of infection or non-severe malaria. Here, we investigated whether cord blood IgG to Plasmodium falciparum merozoite antigens and antibody-mediated effector functions were associated with reduced odds of developing severe malaria at different time points during the first year of life. We conducted a case-control study of well-defined severe falciparum malaria nested within a longitudinal birth cohort of Kenyan children. We measured cord blood total IgG levels against five recombinant merozoite antigens and antibody function in the growth inhibition activity and neutrophil antibody-dependent respiratory burst assays. We also assessed the decay of maternal antibodies during the first 6months of life. The mean antibody half-life range was 2.51months (95% confidence interval (CI): 2.19-2.92) to 4.91months (95% CI: 4.47-6.07). The rate of decline of maternal antibodies was inversely proportional to the starting concentration. The functional assay of antibody-dependent respiratory burst activity predicted significantly reduced odds of developing severe malaria during the first 6months of life (Odds ratio (OR) 0.07, 95% CI: 0.007-0.74, P=0.007). Identification of the targets of antibodies mediating antibody-dependent respiratory burst activity could contribute to the development of malaria vaccines that protect against severe episodes of malaria in early infancy

Dynamics and role of antibodies to Plasmodium falciparum merozoite antigens in children living in two settings with differing malaria transmission intensity

AbstractBackgroundYoung infants have reduced susceptibility to febrile malaria compared with older children, but the mechanism for this remains unclear. There are conflicting data on the role of passively acquired antibodies. Here, we examine antibody titres to merozoite surface antigens in the protection of children in their first two years of life in two settings with differing malaria transmission intensity and compare these titres to previously established protective thresholds.MethodsTwo cohorts of children aged four to six weeks were recruited in Banfora, Burkina and Keur Soce, Senegal and followed up for two years. Malaria infections were detected by light microscopic examination of blood smears collected at active and passive case detection visits. The titres of antibodies to the Plasmodium falciparum recombinant merozoite proteins (AMA1-3D7, MSP1-19, MSP2-Dd2, and MSP3-3D7) were measured by enzyme-linked immunosorbent assay at 1–6, 9, 12, 15 and 18 months of age and compared with the protective thresholds established in Kenyan children.ResultsAntibody titres were below the protective thresholds throughout the study period and we did not find any association with protection against febrile malaria. Antibodies to AMA1 and MSP1-19 appeared to be markers of exposure in the univariate analysis (and so associated with increasing risk) and adjusting for exposure reduced the strength and significance of this association.ConclusionThe antibody levels we measured are unlikely to be responsible for the apparent protection against febrile malaria seen in young infants. Further work to identify protective antibody responses might include functional assays and a wider range of antigens

Design and methods for a quasi-experimental pilot study to evaluate the impact of dual active ingredient insecticide-treated nets on malaria burden in five regions in sub-Saharan Africa

Background:Vector control tools have contributed significantly to a reduction in malaria burden since 2000, primar‑ily through insecticidal‑treated bed nets (ITNs) and indoor residual spraying. In the face of increasing insecticide resist‑ance in key malaria vector species, global progress in malaria control has stalled. Innovative tools, such as dual active ingredient (dual‑AI) ITNs that are effective at killing insecticide‑resistant mosquitoes have recently been introduced. However, large‑scale uptake has been slow for several reasons, including higher costs and limited evidence on their incremental effectiveness and cost‑effectiveness. The present report describes the design of several observational studies aimed to determine the effectiveness and cost‑effectiveness of dual‑AI ITNs, compared to standard pyre‑throid‑only ITNs, at reducing malaria transmission across a variety of transmission settings.Methods:Observational pilot studies are ongoing in Burkina Faso, Mozambique, Nigeria, and Rwanda, leveraging dual‑AI ITN rollouts nested within the 2019 and 2020 mass distribution campaigns in each country. Enhanced surveil‑lance occurring in select study districts include annual cross‑sectional surveys during peak transmission seasons, monthly entomological surveillance, passive case detection using routine health facility surveillance systems, and studies on human behaviour and ITN use patterns. Data will compare changes in malaria transmission and disease burden in districts receiving dual‑AI ITNs to similar districts receiving standard pyrethroid‑only ITNs over three years. The costs of net distribution will be calculated using the provider perspective including financial and economic costs, and a cost‑effectiveness analysis will assess incremental cost‑effectiveness ratios for Interceptor® G2, Royal Guard®, and piperonyl butoxide ITNs in comparison to standard pyrethroid‑only ITNs, based on incidence rate ratios calcu‑lated from routine data.Conclusions:Evidence of the effectiveness and cost‑effectiveness of the dual‑AI ITNs from these pilot studies will complement evidence from two contemporary cluster randomized control trials, one in Benin and one in Tanzania, to provide key information to malaria control programmes, policymakers, and donors to help guide decision‑making and planning for local malaria control and elimination strategies. Understanding the breadth of contexts where these dual‑AI ITNs are most effective and collecting robust information on factors influencing comparative effectiveness could improve uptake and availability and help maximize their impact

La gratuité des soins chez les enfants de moins de 5 ans a-t-elle réduit les inégalités socio-économiques associées à l'utilisation des centres de santé au Burkina Faso ?

info:eu-repo/semantics/inPres

Quelles sont les déterminants à l’utilisation des services de santé pour les enfants de moins de 5ans après la mise en œuvre de la politique de gratuité au Burkina Faso ?

info:eu-repo/semantics/inPres

Recours aux centres de santé en cas de fièvre chez les enfants de moins de 5 ans :effet de la politique de gratuité au Burkina Faso

info:eu-repo/semantics/inPres

Malaria Case Fatality Rate among Children under Five in Burkina Faso: An Assessment of the Spatiotemporal Trends Following the Implementation of Control Programs.

Reducing the 2015 level of malaria mortality by 90% by 2030 is a goal set by the World Health Organization (WHO). In Burkina Faso, several malaria control programs proven to be effective were implemented over the last decade. In parallel, the progressive strengthening of the health surveillance system is generating valuable data, which represents a great opportunity for analyzing the trends in malaria burden and assessing the effect of these control programs. Complementary programs were rolled out at different time points and paces, and the present work aims at investigating both the spatial and temporal pattern of malaria case fatality rate (mCFR) by considering the effect of combining specific and unspecific malaria control programs. To this end, data on severe malaria cases and malaria deaths, aggregated at health district level between January 2013 and December 2018, were extracted from the national health data repository (ENDOS-BF). A Bayesian spatiotemporal zero-inflated Poisson model was fitted to quantify the strength of the association of malaria control programs with monthly mCFR trends at health district level. The model was adjusted for contextual variables. We found that monthly mCFR decreased from 2.0 (95% IC 1.9-2.1%) to 0.9 (95% IC 0.8-1.0%) deaths for 100 severe malaria cases in 2013 and 2018, respectively. Health districts with high mCFR were identified in the northern, northwestern and southwestern parts of the country. The availability of malaria rapid diagnosis tests (IRR: 0.54; CrI: 0.47, 0.62) and treatment (IRR: 0.50; CrI: 0.41, 0.61) were significantly associated with a reduction in the mCFR. The risk of dying from malaria was lower in the period after the free healthcare policy compared with the period before (IRR: 0.47; CrI: 0.38, 0.58). Our findings highlighted locations that are most in need of targeted interventions and the necessity to sustain and strengthen the launched health programs to further reduce the malaria deaths in Burkina Faso.info:eu-repo/semantics/publishe

Using the first nationwide survey on non-communicable disease risk factors and different definitions to evaluate the prevalence of metabolic syndrome in Burkina Faso.

The burden of cardiovascular diseases is rising in the developing world including Sub-Saharan Africa. The rapid rise of cardiovascular disease burden is in part due to undetected and uncontrolled cardiovascular risk factors. The clustering of metabolic syndrome (MetS) components is associated with a high risk of cardiovascular diseases. This complex biochemical disorder is still poorly studied in western Africa. In this study, we aimed to determine the prevalence of metabolic syndrome and its determinants among the adult population in Burkina Faso.info:eu-repo/semantics/publishe

Malaria Case Fatality Rate among Children under Five in Burkina Faso: An Assessment of the Spatiotemporal Trends Following the Implementation of Control Programs.

Reducing the 2015 level of malaria mortality by 90% by 2030 is a goal set by the World Health Organization (WHO). In Burkina Faso, several malaria control programs proven to be effective were implemented over the last decade. In parallel, the progressive strengthening of the health surveillance system is generating valuable data, which represents a great opportunity for analyzing the trends in malaria burden and assessing the effect of these control programs. Complementary programs were rolled out at different time points and paces, and the present work aims at investigating both the spatial and temporal pattern of malaria case fatality rate (mCFR) by considering the effect of combining specific and unspecific malaria control programs. To this end, data on severe malaria cases and malaria deaths, aggregated at health district level between January 2013 and December 2018, were extracted from the national health data repository (ENDOS-BF). A Bayesian spatiotemporal zero-inflated Poisson model was fitted to quantify the strength of the association of malaria control programs with monthly mCFR trends at health district level. The model was adjusted for contextual variables. We found that monthly mCFR decreased from 2.0 (95% IC 1.9-2.1%) to 0.9 (95% IC 0.8-1.0%) deaths for 100 severe malaria cases in 2013 and 2018, respectively. Health districts with high mCFR were identified in the northern, northwestern and southwestern parts of the country. The availability of malaria rapid diagnosis tests (IRR: 0.54; CrI: 0.47, 0.62) and treatment (IRR: 0.50; CrI: 0.41, 0.61) were significantly associated with a reduction in the mCFR. The risk of dying from malaria was lower in the period after the free healthcare policy compared with the period before (IRR: 0.47; CrI: 0.38, 0.58). Our findings highlighted locations that are most in need of targeted interventions and the necessity to sustain and strengthen the launched health programs to further reduce the malaria deaths in Burkina Faso