Search

Toussaint Rouamba,1,2 Paul Sondo,1 Karim Derra,1 Seydou Nakanabo-Diallo,1,3 Biebo Bihoun,1 Eli Rouamba,1 Zekiba Tarnagda,1 Adama Kazienga,1 Innocent Valea,1 Hermann Sorgho,1 Franco Pagnoni,4 Fati Samadoulougou-Kirakoya,2 Halidou Tinto1 1Clinical Research Unit of Nanoro, Institut de Recherche en Sciences de la Santé, Centre National de la Recherche Scientifique et Technologique, Ouagadougou, Burkina Faso; 2Center for Research in Epidemiology, Biostatistics and Clinical Research, School of Public Health, Université Libre de Bruxelles (ULB), Bruxelles, Belgium; 3Department of Clinical Research, Centre Muraz, Bobo-Dioulasso, Burkina Faso; 4World Health Organization, Geneva, SwitzerlandCorrespondence: Toussaint RouambaClinical Research Unit of Nanoro, Institut de Recherche en Sciences de la Santé, Centre National de la Recherche Scientifique et Technologique, 42, Avenue Kumda-Yonre, 11 BP 218 Ouaga CMS 11, Ouagadougou, Burkina FasoTel +226 6665 3204Email rouambatoussaint@gmail.comBackground and purpose: Resource-limited countries face challenges in setting up effective pharmacovigilance systems. This study aimed to monitor the occurrence of adverse events (AEs) after the use of artemisinin-based combination therapies (ACTs), identify potential drivers of reporting suspected adverse drug reactions (ADRs) and monitor AEs among women who were inadvertently exposed to ACTs in the first trimester of pregnancy.Patients and methods: We conducted a prospective observational study from May 2010 to July 2012 in Nanoro Health and Demographic Surveillance System (HDSS), Burkina Faso. The HDSS area was divided into active and passive surveillance areas to monitor AEs among patients (regardless of age or sex) who received a first-line ACT (artemether–lumefantrine or artesunate–amodiaquine). In the active surveillance area, patients were followed up for 28 days, while in the passive surveillance area, patients were encouraged to return voluntarily to the health facility to report any occurrence of AEs until day 28 after drug intake. We assessed the crude incidence rates of AEs in both cohorts and performed Cox regression with mixed random effects to identify potential drivers of ADR occurrence.Results: In total, 3170 participants were included in the study. Of these, 40.3% had reported at least one AE, with 39.6% and 44.4% from active and passive surveillance groups, respectively. The types of ADRs were similar in both groups. The most frequent reported ADRs were anorexia, weakness, cough, dizziness and pruritus. One case of abortion and eight cases of death were reported, but none of them was related to the ACT. The variance in random factors showed a high variability of ADR occurrence between patients in both groups, whereas variability between health facilities was low in the active surveillance group and high in passive surveillance group. Taking more than two concomitant medications was associated with high hazard in ADR occurrence, whereas the rainy season was associated with low hazard.Conclusion: This study showed that both passive and active surveillance approaches were useful tools. The HDSS allowed us to capture a few cases of exposure during the first trimester of pregnancy. The passive surveillance approach, which is more likely to be implemented by malaria control programs, seems to be more relevant in the Sub-Saharan African context.Keywords: HDSS, artemisinin-based combination therapies, safety, pregnancy, malaria, rural, Burkina Faso

Copyright of Médecine et Santé Tropicales is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

2008;7:7. BACKGROUND: Vitamin A and zinc are crucial for normal immune function, and may play a synergistic role for reducing the risk of infection including malaria caused by Plasmodium falciparum. [...]

Background: The emergence of resistance to artemisinin derivatives in western Cambodia is threatening to revert the recent advances made toward global malaria control and elimination. Known resistance-mediating polymorphisms in the K13, pfcrt, pfmdr1, pfdhfr, and pfdhps genes are of greatest importance for monitoring the spread of antimalarial drug resistance. Methods: Samples for the present study were collected from 244 patients with uncomplicated malaria in health centers of Bobo-Dioulasso, Burkina Faso. Blood sample was collected on filter paper before the subject received any treatment. The parasite DNA was then extracted and amplified by Polymerase Chain Reaction (PCR) to evaluate the prevalence of polymorphism of pfcrtK76T, pfmdr1 (N86Y, Y184F), and pfdhps (A437G, K540E). The K13 gene polymorphism was analyzed by nested PCR followed by sequencing. Results: The overall results showed 2.26% (5/221) of K13 synonymous mutant alleles (two C469C, one Y493Y, one G496G, and one V589V), 24.78%, 19.58%, 68.75%, 60.9%, 53.7%, 63.8%, and 64.28%, respectively, for mutant pfcrt 76T, pfmdr1-86Y, pfmdr1-184F, pfdhfr51I, pfdhfr59R, pfdhfr108N, and pfdhps 437G. We did not report any mutation at codon 540 of pfdhps. Conclusion: These results provide baseline prevalence of known drug resistance polymorphisms and suggest that artemisinin combination therapies may retain good efficacy in the treatment of uncomplicated malaria in Burkina Faso.

Abstract Background A prospective study aiming at assessing the effect of adding a third dose sulphadoxine-pyrimethamine (SP) to the standard two-dose intermittent preventive treatment for pregnant women was carried out in Hounde, Burkina Faso, between March 2006 and July 2008. Pregnant women were identified as earlier as possible during pregnancy through a network of home visitors, referred to the health facilities for inclusion and followed up until delivery. Methods Study participants were enrolled at antenatal care (ANC) visits and randomized to receive either two or three doses of SP at the appropriate time. Women were visited daily and a blood slide was collected when there was fever (body temperature > 37.5°C) or history of fever. Women were encouraged to attend ANC and deliver in the health centre, where the new-born was examined and weighed. The timing and frequency of malaria infection was analysed in relation to the risk of low birth weight, maternal anaemia and perinatal mortality. Results Data on birth weight and haemoglobin were available for 1,034 women. The incidence of malaria infections was significantly lower in women having received three instead of two doses of SP. Occurrence of first malaria infection during the first or second trimester was associated with a higher risk of low birth weight: incidence rate ratios of 3.56 (p < 0.001) and 1.72 (p = 0.034), respectively. After adjusting for possible confounding factors, the risk remained significantly higher for the infection in the first trimester of pregnancy (adjusted incidence rate ratio = 2.07, p = 0.002). The risk of maternal anaemia and perinatal mortality was not associated with the timing of first malaria infection. Conclusion Malaria infection during first trimester of pregnancy is associated to a higher risk of low birth weight. Women should be encouraged to use long-lasting insecticidal nets before and throughout their pregnancy.

Abstract Background Vitamin A and zinc are crucial for normal immune function, and may play a synergistic role for reducing the risk of infection including malaria caused by Plasmodium falciparum. Methods A randomized, double-blind, placebo-controlled trial of a single dose of 200 000 IU of vitamin A with daily zinc supplementation was done in children of Sourkoudougou village, Burkina Faso. Children aged from 6 to 72 months were randomized to receive a single dose of 200 000 IU of vitamin A plus 10 mg elemental zinc, six days a week (n = 74) or placebo (n = 74) for a period of six months. Cross-sectional surveys were conducted at the beginning and the end of the study, and children were evaluated daily for fever. Microscopic examination of blood smear was done in the case of fever (temperature ≥37.5°C) for malaria parasite detection. Results At the end of the study we observed a significant decrease in the prevalence malaria in the supplemented group (34%) compared to the placebo group (3.5%) (p < 0.001). Malaria episodes were lower in the supplemented group (p = 0.029), with a 30.2% reduction of malaria cases (p = 0.025). Time to first malaria episode was longer in the supplemented group (p = 0.015). The supplemented group also had 22% fewer fever episodes than the placebo group (p = 0.030). Conclusion These results suggest that combined vitamin A plus zinc supplementation reduces the risk of fever and clinical malaria episodes among children, and thus may play a key role in malaria control strategies for children in Africa.

Background: Vitamin A and zinc are crucial for normal immune function, and may play a synergistic role for reducing the risk of infection including malaria caused by Plasmodium falciparum.Methods: A randomized, double-blind, placebo-controlled trial of a single dose of 200 000 IU of vitamin A with daily zinc supplementation was done in children of Sourkoudougou village, Burkina Faso. Children aged from 6 to 72 months were randomized to receive a single dose of 200 000 IU of vitamin A plus 10 mg elemental zinc, six days a week (n = 74) or placebo (n = 74) for a period of six months. Cross-sectional surveys were conducted at the beginning and the end of the study, and children were evaluated daily for fever. Microscopic examination of blood smear was done in the case of fever (temperature > or =37.5 degrees C) for malaria parasite detection.Results: At the end of the study we observed a significant decrease in the prevalence malaria in the supplemented group (34%) compared to the placebo group (3.5%) (p < 0.001). Malaria episodes were lower in the supplemented group (p = 0.029), with a 30.2% reduction of malaria cases (p = 0.025). Time to first malaria episode was longer in the supplemented group (p = 0.015). The supplemented group also had 22% fewer fever episodes than the placebo group (p = 0.030).Conclusion: These results suggest that combined vitamin A plus zinc supplementation reduces the risk of fever and clinical malaria episodes among children, and thus may play a key role in malaria control strategies for children in Africa. [ABSTRACT FROM AUTHOR]

Background: The hormonal shift occurring in pregnant women is crucial for the outcome of pregnancy. We conducted a study in pregnant women living in a malaria endemic area to determine the potential effect of gestational age on the modulation of the endocrine system by cortisol and prolactin production during pregnancy., Methods: Primigravidae and multigravidae with a gestational age between 16-20 weeks were included in the study and followed up to delivery and 6-7 weeks thereafter. Venous blood was collected at scheduled visit: Visit 1 (V1; 16-20 weeks of amenorrhea), Visit 2 (V2; 28 ±1 weeks of pregnancy), Visit 3 (V3; 32 ±1 weeks of pregnancy), Visit4 (V4; delivery) and Visit5 (V5; 6-7 weeks after delivery). In addition, a cord blood sample was also collected during labour at delivery. Nulliparous and primiparous/multiparous non-pregnant women were enrolled in the control group. Cortisol and prolactin plasma concentrations were measured using ichroma II and i-chamber apparatus. Light microscopy was used to detect Plasmodium falciparum infections. A linear mixed-effects regression (LMER) model was used to assess the association between the variation of cortisol titres and prolactin levels during the pregnancy and the post-partum., Results: Results showed that cortisol and prolactin levels in the peripheral blood were globally up-regulated during pregnancy. Concentrations of cortisol during follow-up was significantly higher in primigravidae than in multigravidae during the whole pregnancy (p<0.024). Moreover, the level of prolactin which was higher before delivery in primigravidae reversed at delivery and postpartum visit, but the difference was not statistically significant during the follow-up (V1 to V5) (p = 0.60). The cortisol level in peripheral blood at delivery was higher than that in the cord blood, and conversely for prolactin. Cortisol and prolactin levels decreased after delivery, though the level of prolactin was still higher than that at enrolment. An increase of one unit of prolactin was associated with the decrease of the average concentration of cortisol by 0.04 ng/ml (p = 0.009). However, when cortisol increases with one unit, the average concentration of prolactin decreases by 1.16 ng/ml (p = 0.013)., Conclusion: These results showed that the up-regulation effects of cortisol and prolactin are related to gestational age. A The downward regulation effect that both hormones have on each other during the pregnancy when each increase to 1 unit (1.0 ng/ml) was also reported., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kiemde et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The RTS,S/AS01 E malaria vaccine showed lower antibody response and protective efficacy in infants aged 6-12 weeks compared with children aged 5-17 months (for whom this vaccine is recommended). We aimed to study the effect of previous Plasmodium falciparum exposure on the antibody responses to RTS,S/AS01 E vaccination in infants and children, and the mediating effect of baseline (including maternal) anti-circumsporozoite protein (CSP) antibodies., Methods: In this observational study, we included children and infants from six African countries (Burkina Faso, Gabon, Ghana, Kenya, Mozambique, and Tanzania) enrolled in the MAL067 immunology ancillary study of the RTS,S/AS01 E phase 3 clinical trial from March 27, 2009, to Jan 21, 2011. We used comparator-vaccinated infants and children to identify antibody-based signatures of previous P falciparum exposure, which were later applied to RTS,S/AS01 E -vaccinated infants and children. In these participants, we explored the relationship between vaccine antibody immunoglobulin G (IgG) responses measured by ELISA and pre-vaccination serological markers of malaria exposure by assessing the IgG levels against 1000 P falciparum antigens using partial proteome microarrays., Findings: We included 718 comparator-vaccinated infants (348 [48%]) and children (370 [52%]) and 606 RTS,S/AS01 E -vaccinated infants (329 [54%]) and children (277 [46%]). Anti-CSP IgG responses to primary vaccination did not correlate with a baseline signature of previous exposure in children, suggesting that prior P falciparum exposure does not significantly affect antibody immunogenicity in children (Pearson's r=-0·02 [95% CI -0·13 to 0·10]). By contrast, high P falciparum exposure signature levels at the time of vaccination in infants, presumably driven by maternally transferred antibodies and declining within the initial 6-12 months of life, correlated with reduced RTS,S/AS01 E responses (r=-0·17 [-0·27 to -0·06]). This negative correlation was stronger for anti-CSP IgG than for the exposure signature or any other more immunogenic blood stage P falciparum antigens (r=-0·42 [-0·50 to -0·33]), persisted after adjustment by baseline levels of the exposure signature (semi-partial correlation r=-0·44 [-0·55 to -0·33]), and involved antibodies to the central NANP region (r=-0·39 [-0·49 to -0·28]) but not the C-terminal region (r=0·02 [-0·10 to 0·15]) of CSP. The negative effect of maternal anti-CSP IgG in infants did not appear to be confounded by other malaria transmission-dependent variables., Interpretation: Interference between passive immunity and vaccine response is clinically significant and might affect the implementation of next-generation CSP-based vaccines for young infants and mothers as well as passive immunisation with human monoclonal antibodies., Funding: US National Institutes of Health, National Institute of Allergy and Infectious Diseases; PATH-Malaria Vaccine Initiative; Spanish Ministerio de Economía y Competitividad (Instituto de Salud Carlos III), European Regional Development Fund and European Social Fund; Fundación Ramón Areces; Spanish Ministry of Science and Innovation; and Generalitat de Catalunya (CERCA Program)., Competing Interests: Declaration of interests JJC is an employee of Antigen Discovery, a company that carries patents (US Patent 10174311 and US Patent 20160320404) related to the protein microarray analyses used here and where the arrays were conducted. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Genome-wide association studies (GWAS) have predominantly focused on populations of European and Asian ancestry, limiting our understanding of genetic factors influencing kidney disease in Sub-Saharan African (SSA) populations. This study presents the largest GWAS for urinary albumin-to-creatinine ratio (UACR) in SSA individuals, including 8,970 participants living in different African regions and an additional 9,705 non-resident individuals of African ancestry from the UK Biobank and African American cohorts., Methods: Urine biomarkers and genotype data were obtained from two SSA cohorts (AWI-Gen and ARK), and two non-resident African-ancestry studies (UK Biobank and CKD-Gen Consortium). Association testing and meta-analyses were conducted, with subsequent fine-mapping, conditional analyses, and replication studies. Polygenic scores (PGS) were assessed for transferability across populations., Results: Two genome-wide significant (P < 5 × 10 -8 ) UACR-associated loci were identified, one in the BMP6 region on chromosome 6 , in the meta-analysis of resident African individuals, and another in the HBB region on chromosome 11 in the meta-analysis of non-resident SSA individuals, as well as the combined meta-analysis of all studies. Replication of previous significant results confirmed associations in known UACR-associated regions, including THB53 , GATM, and ARL15 . PGS estimated using previous studies from European ancestry, African ancestry, and multi-ancestry cohorts exhibited limited transferability of PGS across populations, with less than 1% of observed variance explained., Conclusion: This study contributes novel insights into the genetic architecture of kidney disease in SSA populations, emphasizing the need for conducting genetic research in diverse cohorts. The identified loci provide a foundation for future investigations into the genetic susceptibility to chronic kidney disease in underrepresented African populations Additionally, there is a need to develop integrated scores using multi-omics data and risk factors specific to the African context to improve the accuracy of predicting disease outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer HQ declared a past collaboration with the authors MR to the handling editor., (Copyright © 2024 Brandenburg, Chen, Boua, Govender, Agongo, Micklesfield, Sorgho, Tollman, Asiki, Mashinya, Hazelhurst, Morris, Fabian and Ramsay.)

Background: The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa., Methods: We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12-18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2-10 years (PfPR 2-10 ) and ranges from 3% to 65% PfPR 2-10 ., Findings: Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815-333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868-405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of US$3, the incremental cost per clinical case averted was $7 (range 4-48) in perennial settings and $6 (3-63) in seasonal settings and the incremental cost per DALY averted was $34 (29-139) in perennial settings and $30 (22-172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR 2-10 ., Interpretation: Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa., Funding: The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy., Competing Interests: Declaration of interests AVSH and KJE are named as co-inventors on patent applications related to R21 and are entitled to a royalty share on any future income in conformity with the University of Oxford's policy. KJE was an employee of the University of Oxford at the time of the work and is now an employee of GSK. KJE holds restricted shares in the GSK group of companies. The University of Oxford has received funding from the Serum Institute of India to support funding of several African trials including the ongoing phase 3 trial of R21/Matrix-M. AVSH is chief investigator of these trials. PW has received funding from Gavi and the Wellcome Trust in the past 36 months. ACG has received funding from Gavi and NIH and consulting fees from the Global Fund in the past 36 months and is a trustee at Malaria No More UK. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: anemia, the commonest nutritional deficiency disorder among pregnant women in sub-Saharan Africa, is associated with severe peripartum complications. Its regular monitoring is necessary to timely inform clinical and preventive decision-making. The aim of this study was to assess the prevalence and determinants of anemia among pregnant women in rural areas of Burkina Faso., Methods: between August 2019 and March 2020, a cross-sectional study was conducted to collect maternal sociodemographic, gynaeco-obstetric, and medical characteristics by face-to-face interview or by review of antenatal care books. In addition, maternal malaria was diagnosed by standard microscopy and the hemoglobin levels (Hb) measured by spectrophotometry. The proportion of anaemia (Hb<11.0 g/dL), moderate (7.0

Most hypertension-related genome-wide association studies (GWASs) focus on non-African populations, despite hypertension (a major risk factor for cardiovascular disease) being highly prevalent in Africa. The AWI-Gen study GWAS meta-analysis for blood pressure (BP)-related traits (systolic and diastolic BP, pulse pressure, mean-arterial pressure and hypertension) from three sub-Saharan African geographic regions (N = 10,775), identifies two novel genome-wide significant signals (p < 5E-08): systolic BP near P2RY1 (rs77846204; intergenic variant, p = 4.95E-08) and pulse pressure near LINC01256 (rs80141533; intergenic variant, p = 1.76E-08). No genome-wide signals are detected for the AWI-Gen GWAS meta-analysis with previous African-ancestry GWASs (UK Biobank (African), Uganda Genome Resource). Suggestive signals (p < 5E-06) are observed for all traits, with 29 SNPs associating with more than one trait and several replicating known associations. Polygenic risk scores (PRSs) developed from studies on different ancestries have limited transferability, with multi-ancestry PRS providing better prediction. This study provides insights into the genetics of BP variation in African populations., (© 2023. The Author(s).)

Background: "Choosing All Together" (CHAT), is a community engagement tool designed to give the public a voice in how best to allocate limited resources to improve population health. This process evaluation explored the mechanisms through which CHAT generates community engagement., Method: The CHAT tool was adapted and implemented for use in two rural communities (Nanoro, Burkina Faso, and Navrongo, Ghana) and one urban township (Soweto, South Africa) to prioritize maternal and child nutrition interventions. Community discussions were audio-recorded, transcribed, and translated into English. Twenty-two transcripts, including six each from Navrongo and Soweto and 10 from Nanoro, were analysed thematically to generate data driven codes and themes to explain mechanisms underlying the CHAT process. The process evaluation was based on the UK MRC process evaluation guidance., Results: Seven themes describing the functions and outcomes of CHAT were identified. Themes described participants deliberating trade-offs, working together, agreeing on priorities, having a shared vision, and increasing their knowledge, also the skills of the facilitator, and a process of power sharing between participants and researchers. Participants came to an agreement of priorities when they had a shared vision. Trained facilitators are important to facilitate meaningful discussion between participants and those with lower levels of literacy to participate fully., Conclusion: CHAT has been shown to be adaptable and useful in prioritising maternal and child nutrition interventions in communities in Burkina Faso, Ghana, and South Africa. Conducting CHAT in communities over a longer period and involving policy-makers would increase trust, mutual respect and develop partnerships., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Watson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this study, we investigated how different categories of prenatal malaria exposure (PME) influence levels of maternal antibodies in cord blood samples and the subsequent risk of malaria in early childhood in a birth cohort study ( N = 661) nested within the COSMIC clinical trial (NCT01941264) in Burkina Faso. Plasmodium falciparum infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. The levels of maternal IgG and IgG 1-4 to 15 P . falciparum antigens were measured in cord blood by quantitative suspension array technology. Results showed a significant variation in the magnitude of maternal antibody levels in cord blood, depending on the PME category, with past placental malaria (PM) more frequently associated with significant increases of IgG and/or subclass levels across three groups of antigens defined as pre-erythrocytic, erythrocytic, and markers of PM, as compared to those from the cord of non-exposed control infants. High levels of antibodies to certain erythrocytic antigens (i.e., IgG to EBA140 and EBA175, IgG1 to EBA175 and MSP1 42 , and IgG3 to EBA140 and MSP5) were independent predictors of protection from clinical malaria during the first year of life. By contrast, high levels of IgG, IgG1, and IgG2 to the VAR2CSA DBL1-2 and IgG4 to DBL3-4 were significantly associated with an increased risk of clinical malaria. These findings indicate that PME categories have different effects on the levels of maternal-derived antibodies to malaria antigens in children at birth, and this might drive heterogeneity to clinical malaria susceptibility in early childhood., Competing Interests: The authors declare no conflict of interest.

The global burden of undernutrition remains high, responsible for significant under-five mortality in resource-limited settings. Numerous sustainable development goals (SDGs) are linked to nutrition, and nationally representative nutrition surveillance is a key activity to track progress towards SDGs and guide efficient programmes., Objectives: The aim of this study is to look at spatial and temporal trends in undernutrition in children under 5 years age in Burkina Faso., Setting: We used data from annual National Nutrition Surveys using Standardised Monitoring and Assessment of Relief and Transitions methodology (anthropometry, morbidity) over 7 years (2012-2018) in Burkina Faso., Participants: Children of under 5 years from households selected through systemic sampling at countrywide level., Main Outcome Measures: Prevalence of stunting (height-for-age z-score, <-2), underweight (weight-for-age z-score, <-2) and wasting (weight-for-height z-score, <-2) at regional and national. We used general linear mixed models, adjusted by age, survey year, sex, presence of fever and/or diarrhoea, and poverty index to quantify the risk of undernutrition over time and by region of residence., Results: Between 2012 and 2018, decreases were observed overall in the prevalence of growth retardation (stunting) decreased from 33.0% (95% CI 32.3 to 33.8) in 2012 to 26.7% (95% CI 26.2 to 27.3) in 2018. Underweight reduced from 24.4% (95% CI 23.7 to 25.1) to 18.7% (95% CI 18.2 to 19.2) for the same period and wasting decreased from 10.8% (95% CI 10.3 to 11.3) in 2012 to 8.4% (95% CI 8.1 to 8.8) in 2018. However, there was substantial variation across the country, with increased risk of undernutrition in the regions of Sahel, East and Cascades primarily. High-risk regions were characterised by a lower poverty index and limited access to healthcare services., Conclusions: Our findings could inform national policymakers in refining and optimising resource allocation based on the identification of high-risk areas., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Malaria is still one of the main reasons for hospitalization in children living in sub-Saharan Africa. Rapid risk stratification at admission is essential for optimal medical care and improved prognosis. Whereas coma, deep breathing, and, to a lesser degree, severe anemia are established predictors of malaria-related death, the value of assessing prostration for risk stratification is less certain., Methods: Here we used a retrospective multi-center analysis comprising over 33,000 hospitalized children from four large studies, including two observational studies from the Severe Malaria in African Children network, a randomized controlled treatment study, and the phase-3-clinical RTS,S-malaria vaccine trial, to evaluate known risk factors of mortality and with a specific emphasis on the role of prostration., Results: Despite comparable age profiles of the participants, we found significant inter- and intra-study variation in the incidence of fatal malaria as well as in the derived risk ratios associated with the four risk factors: coma, deep breathing, anemia, and prostration. Despite pronounced variations, prostration was significantly associated with an increased risk of mortality (P <0.001) and its consideration resulted in improved predictive performance, both in a multivariate model and a univariate model based on the Lambaréné Organ Dysfunction Score., Conclusion: Prostration is an important clinical criterion to determine severe pediatric malaria with possible fatal outcomes., Competing Interests: Declarations of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The first 1000 days of life are a critical period of growth and development that have lasting implications for health, cognitive, educational and economic outcomes. In sub-Saharan Africa, gender and social norms are such that many men have little engagement with maternal and child health and nutrition during pregnancy and early childhood. This study explores how men perceive their role in three sites in sub-Saharan Africa., Methods: Secondary qualitative analysis of 10 focus group discussions with 76 men in Burkina Faso, Ghana and South Africa. Data were thematically analysed to explore men's perceptions of maternal and child health and nutrition., Results: Men considered themselves 'providers' and 'advisors' within their families, particularly of finances, food and medicines. They also indicated that this advice was out of care and concern for their families' health. There were similarities in how the men perceive their role. Differences between men living in rural and urban settings included health priorities, the advice and the manner in which it was provided. Across all settings, men wanted to be more involved with maternal and child health and nutrition. Challenges to doing so included stigma and proscribed social gender roles., Conclusion: Men want a greater engagement in improving maternal and child health and nutrition but felt that their ability to do so was limited by culture-specified gender roles, which are more focused on providing for and advising their families. Involving both men and women in intervention development alongside policymakers, health professionals and researchers is needed to improve maternal and child health and nutrition., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In this study, we evaluated the performance of a P. falciparum Histidine Rich Protein 2 ( Pf HRP2)-based rapid diagnostic test (RDT) used for malaria case detection (SD-Bioline malaria RDT P.f ® ) along with light microscopy (LM) against qPCR among children during the first year of life in a high and seasonal malaria transmission area in Burkina Faso. A total of 723 suspected malaria cases (including multiple episodes) that occurred among 414 children participating in a birth-cohort study were included in the present analysis. Factors including age at the time of malaria screening, transmission season and parasite densities were investigated for their potential influence in the performance of the RDT. Clinical malaria cases as detected by RDT, LM and qPCR were 63.8%, 41.5% and 49.8%, respectively. Compared with qPCR, RDT had a false-positive results rate of 26.7%, resulting in an overall accuracy of 79.9% with a sensitivity of 93%, a specificity of 66.1%, a Positive Predictive Value of 73.3% and a Negative Predictive Value of 91.6%. Its specificity differed significantly between high and low transmission seasons (53.7% vs 79.8%; P  < 0.001) and decreased with increasing age (80.6-62%; P for trend = 0.024). The overall accuracy of LM was 91.1% and its performance was not significantly influenced by transmission season or age. These findings highlight the need to adapt malaria diagnostic tools recommendations to face the challenge of adequate malaria detection in this population group living in high burden and seasonal malaria transmission settings., Competing Interests: Conflict of interestThe authors have no relevant financial or non-financial interests to disclose., (© Indian Society for Parasitology 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objectives: We investigated progression through the care cascade and associated factors for people with diabetes in sub-Saharan Africa to identify attrition stages that may be most appropriate for targeted intervention., Design: Cross-sectional study., Setting: Community-based study in four sub-Saharan African countries., Participants: 10 700 individuals, aged 40-60 years., Primary and Secondary Outcome Measures: The primary outcome measure was the diabetes cascade of care defined as the age-adjusted diabetes prevalence (self-report of diabetes, fasting plasma glucose (FPG) ≥7 mmol/L or random plasma glucose ≥11.1 mmol/L) and proportions of those who reported awareness of having diabetes, ever having received treatment for diabetes and those who achieved glycaemic control (FPG <7.2 mmol/L). Secondary outcome measures were factors associated with having diabetes and being aware of the diagnosis., Results: Diabetes prevalence was 5.5% (95% CI 4.4% to 6.5%). Approximately half of those with diabetes were aware (54%; 95% CI 50% to 58%); 73% (95% CI 67% to 79%) of aware individuals reported ever having received treatment. However, only 38% (95% CI 30% to 46%) of those ever having received treatment were adequately controlled. Increasing age (OR 1.1; 95% CI 1.0 to 1.1), urban residence (OR 2.3; 95% CI 1.6 to 3.5), hypertension (OR 1.9; 95% CI 1.5 to 2.4), family history of diabetes (OR 3.9; 95% CI 3.0 to 5.1) and measures of central adiposity were associated with higher odds of having diabetes. Increasing age (OR 1.1; 95% CI 1.0 to 1.1), semi-rural residence (OR 2.5; 95% CI 1.1 to 5.7), secondary education (OR 2.4; 95% CI 1.2 to 4.9), hypertension (OR 1.6; 95% CI 1.0 to 2.4) and known HIV positivity (OR 2.3; 95% CI 1.2 to 4.4) were associated with greater likelihood of awareness of having diabetes., Conclusions: There is attrition at each stage of the diabetes care cascade in sub-Saharan Africa. Public health strategies should target improving diagnosis in high-risk individuals and intensifying therapy in individuals treated for diabetes., Competing Interests: Competing interests: ANW declares an honorarium received from Sanofi for serving as a panel member at an educational event on thyroid cancer. SAN declares participation in a data safety monitoring board of a Phase IV open-label trial to assess bone mineral density in a cohort of African women on Depo-Provera and tenofovir disoproxil fumarate switched to tenofovir alafenamide fumarate based antiretroviral therapy and Council membership in the International Society of Developmental Origins of Health and Disease., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Maternal and early malnutrition have negative health and developmental impacts over the life-course. Consequently, early nutrition support can provide significant benefits into later life, provided the later life contexts allow. This study examines the limits of siloed investments in nutrition and illustrates how ignoring life-course contextual constraints limits human development benefits and exacerbates inequality, particularly in fragile contexts. This case study focuses on Burkina Faso, a country with high rates of early malnutrition and a fragile state. We modelled the impact of scaling up 10 nutrition interventions to 80% coverage for a single year cohort on stunting, nationally and sub-nationally, using the Lives Saved Tool (LiST), and the consequent impact on earnings, without and with a complementary cash-transfer in later life. The impact on earnings was modelled utilising the well-established pathway between early nutrition, years of completed schooling and, consequent adult earnings. Productivity returns were estimated as the present value of increased income over individuals' working lives, then compared to estimates of the present value of providing the cost of nutrition interventions and cash-transfers. The cost benefit ratio at the national level for scaled nutrition alone is 1:1. Sub-nationally the worst-off region yields the lowest ratio < 0.2 for every dollar spent. The combination of nutrition and cash-transfers national cost benefit is 1:12, still with regional variation but with great improvement in the poorest region. This study shows that early nutrition support alone may not be enough to address inequality and may add to state fragility. Taking a life-course perspective when priority-setting in contexts with multiple constraints on development can help to identify interventions that maximizing returns, without worsening inequality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Desmond et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Exposure during pregnancy to malaria and sexually-transmitted infections is associated with adverse birth outcomes including low birth weight (LBW). This study aimed at assessing if the adjunction of two doses of azithromycin to sulfadoxine-pyrimethamine for the intermittent preventive treatment of malaria in pregnancy can reduce LBW., Methods: A two parallel-groups, open-label randomized controlled trial involving pregnant women (16 to 35 years of age and 12 to 24 weeks of gestation as confirmed by last menstrual period or fundal height) was conducted in rural Burkina Faso. Women were assigned in a 1:1 ratio either to use azithromycin (1 g daily for 2 days) during the second and third trimesters of pregnancy plus monthly sulfadoxine-pyrimethamine (1500/75 mg) (SPAZ) (intervention) or to continue using a monthly sulfadoxine-pyrimethamine (1500/75 mg) (SP) (control). Primary outcome was a LBW (birth weight measured within 24 h after birth < 2500 g). Secondary outcomes including stillbirth, preterm birth or miscarriage are reported together with safety data., Results: A total of 992 pregnant women underwent randomization (496 per group) and 898 (90.5%) valid birth weights were available (450 in SPAZ and 448 in SP). LBW incidence was 8.7% (39/450) in SPAZ and 9.4% (42/448) in controls (p-value = 0.79). Compared with controls, pregnant women with SPAZ showed a risk ratio (RR) of 1.16 (95% confidence interval (CI 0.64-2.08]) for preterm births, 0.75 (95% CI 0.17-3.35) for miscarriage and 0.64 (95% CI 0.25-1.64) for stillbirths. No treatment-related serious adverse events (SAEs) have been observed, and there was no significant difference in the number of SAEs (13.5% [67/496] in SPAZ, 16.7% [83/496] in SP, p-value = 0.18) or AEs (17.1% [85/496] in SPAZ, 18.8% [93/496] in SP, p-value = 0.56)., Conclusion: Adequate prevention regimen with monthly sulfadoxine-pyrimethamine given to all pregnant women has been proved to reduce the risk of LBW in malaria endemic areas. Adding azithromycin to the regimen does not offer further benefits, as far as women receive a malaria prevention regimen early enough during pregnancy. Trial registration Pan African Clinical Trial Registry ( https://pactr.samrc.ac.za/Search.aspx ): PACTR201808177464681. Registered 21 August 2018., (© 2023. The Author(s).)

Objectives: To determine the prevalence of multimorbidity, to identify which chronic conditions cluster together and to identify factors associated with a greater risk for multimorbidity in sub-Saharan Africa (SSA)., Design: Cross-sectional, multicentre, population-based study., Setting: Six urban and rural communities in four sub-Saharan African countries., Participants: Men (n=4808) and women (n=5892) between the ages of 40 and 60 years from the AWI-Gen study., Measures: Sociodemographic and anthropometric data, and multimorbidity as defined by the presence of two or more of the following conditions: HIV infection, cardiovascular disease, chronic kidney disease, asthma, diabetes, dyslipidaemia, hypertension., Results: Multimorbidity prevalence was higher in women compared with men (47.2% vs 35%), and higher in South African men and women compared with their East and West African counterparts. The most common disease combination at all sites was dyslipidaemia and hypertension, with this combination being more prevalent in South African women than any single disease (25% vs 21.6%). Age and body mass index were associated with a higher risk of multimorbidity in men and women; however, lifestyle correlates such as smoking and physical activity were different between the sexes., Conclusions: The high prevalence of multimorbidity in middle-aged adults in SSA is of concern, with women currently at higher risk. This prevalence is expected to increase in men, as well as in the East and West African region with the ongoing epidemiological transition. Identifying common disease clusters and correlates of multimorbidity is critical to providing effective interventions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Malaria is a leading cause of morbidity and mortality worldwide. We previously reported the efficacy of the R21/Matrix-M malaria vaccine, which reached the WHO-specified goal of 75% or greater efficacy over 12 months in the target population of African children. Here, we report the safety, immunogenicity, and efficacy results at 12 months following administration of a booster vaccination., Methods: This double-blind phase 1/2b randomised controlled trial was done in children aged 5-17 months in Nanoro, Burkina Faso. Eligible children were enrolled and randomly assigned (1:1:1) to receive three vaccinations of either 5 μg R21/25 μg Matrix-M, 5 μg R21/50 μg Matrix-M, or a control vaccine (the Rabivax-S rabies vaccine) before the malaria season, with a booster dose 12 months later. Children were eligible for inclusion if written informed consent could be provided by a parent or guardian. Exclusion criteria included any existing clinically significant comorbidity or receipt of other investigational products. A random allocation list was generated by an independent statistician by use of block randomisation with variable block sizes. A research assistant from the University of Oxford, independent of the trial team, prepared sealed envelopes using this list, which was then provided to the study pharmacists to assign participants. All vaccines were prepared by the study pharmacists by use of the same type of syringe, and the contents were covered with an opaque label. Vaccine safety, efficacy, and a potential correlate of efficacy with immunogenicity, measured as anti-NANP antibody titres, were evaluated over 1 year following the first booster vaccination. The population in which the efficacy analyses were done comprised all participants who received the primary series of vaccinations and a booster vaccination. Participants were excluded from the efficacy analysis if they withdrew from the trial within the first 2 weeks of receiving the booster vaccine. This trial is registered with ClinicalTrials.gov (NCT03896724), and is continuing for a further 2 years to assess both the potential value of additional booster vaccine doses and longer-term safety., Findings: Between June 2, and July 2, 2020, 409 children returned to receive a booster vaccine. Each child received the same vaccination for the booster as they received in the primary series of vaccinations; 132 participants received 5 μg R21 adjuvanted with 25 μg Matrix-M, 137 received 5 μg R21 adjuvanted with 50 μg Matrix-M, and 140 received the control vaccine. R21/Matrix-M had a favourable safety profile and was well tolerated. Vaccine efficacy remained high in the high adjuvant dose (50 μg) group, similar to previous findings at 1 year after the primary series of vaccinations. Following the booster vaccination, 67 (51%) of 132 children who received R21/Matrix-M with low-dose adjuvant, 54 (39%) of 137 children who received R21/Matrix-M with high-dose adjuvant, and 121 (86%) of 140 children who received the rabies vaccine developed clinical malaria by 12 months. Vaccine efficacy was 71% (95% CI 60 to 78) in the low-dose adjuvant group and 80% (72 to 85) in the high-dose adjuvant group. In the high-dose adjuvant group, vaccine efficacy against multiple episodes of malaria was 78% (95% CI 71 to 83), and 2285 (95% CI 1911 to 2568) cases of malaria were averted per 1000 child-years at risk among vaccinated children in the second year of follow-up. Among these participants, at 28 days following their last R21/Matrix-M vaccination, titres of malaria-specific anti-NANP antibodies correlated positively with protection against malaria in both the first year of follow-up (Spearman's ρ -0·32 [95% CI -0·45 to -0·19]; p=0·0001) and second year of follow-up (-0·20 [-0·34 to -0·06]; p=0·02)., Interpretation: A booster dose of R21/Matrix-M at 1 year following the primary three-dose regimen maintained high efficacy against first and multiple episodes of clinical malaria. Furthermore, the booster vaccine induced antibody concentrations that correlated with vaccine efficacy. The trial is ongoing to assess long-term follow-up of these participants and the value of further booster vaccinations., Funding: European and Developing Countries Clinical Trials Partnership 2 (EDCTP2), Wellcome Trust, and NIHR Oxford Biomedical Research Centre., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests AVSH and KJE are named as co-inventors on patent applications related to R21. GG, LF, and JR are employees of Novavax, developers of the Matrix-M adjuvant. US is an employee of the Serum Institute of India, a co-developer of the R21/Matrix-M vaccine. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Malaria infection during pregnancy (MIP) is not only deleterious to the woman, but it also puts her fetus at increased risk of adverse outcomes, such as preterm delivery, low birth weight, and intrauterine growth retardation. Additionally, all-cause mortality during the first year of life in babies born to women with malaria during pregnancy is also increased. Many interventions such as IPTp-SP and long-lasting insecticidal nets have proven to be efficient at reducing malaria in pregnancy burden but adherence to recommended policies remains poor. In sub-Saharan Africa, malaria in pregnancy is often asymptomatic and many malaria infections may be missed due to the inadequate performance of the current rapid diagnostic test to detect low-level parasitemias. Therefore, additional strategies such as intermittent screening with ultrasensitive rapid diagnostic tests and treatment with an effective artemisinin-based combination therapy in addition to IPTp-SP could reduce placental malaria, peripheral malaria infection at delivery, and low birth weight., Methods: This pilot 2-group randomized open trial with a nested qualitative social behavioral will be carried out in Nanoro district in which 340 pregnant women will be recruited. Pregnant women will be randomized into two groups and followed on a monthly basis until delivery. In the intervention group, monthly screening using ultrasensitive rapid diagnostic tests and treatment of those found to be infected with dihydroartemisinin-piperaquine will be performed. In addition, a reminder will be sent to increase the uptake of IPTp-SP doses per woman. During scheduled and unscheduled visits, malaria infection, hemoglobin level, and other clinical outcomes will be assessed and compared by the group. The primary feasibility outcome will evaluate the study site's capacity to enroll participants and the women's perception and acceptability of the intervention. The primary clinical outcome will be the prevalence of placental malaria at delivery., Discussion: The present protocol aims to evaluate the feasibility on a large-scale and also to demonstrate the impact and the operational feasibility of additional screening with ultrasensitive rapid diagnostic tests and treatment with DHA-PQ on placental malaria, low birth weight, and peripheral malaria infection at delivery in a high-burden setting in Burkina Faso., Trial Registration: ClinicalTrials.gov , ID: NCT04147546 (14 October 2019)., (© 2022. The Author(s).)

Background: Artemisinins (ART) are the key component of the frontline antimalarial treatment, but their impact on Plasmodium falciparum sexual conversion rates in natural malaria infections remains unknown. This is an important knowledge gap because sexual conversion rates determine the relative parasite investment between maintaining infection in the same human host and transmission to mosquitoes., Methods: The primary outcome of this study was to assess the impact of ART-based treatment on sexual conversion rates by comparing the relative transcript levels of pfap2-g and other sexual ring biomarkers (SRBs) before and after treatment. We analysed samples from previously existing cohorts in Vietnam, Burkina Faso and Mozambique (in total, n=109) collected before treatment and at 12 h intervals after treatment. As a secondary objective, we investigated factors that may influence the effect of treatment on sexual conversion rates., Findings: In the majority of infections from the African cohorts, but not from Vietnam, we observed increased expression of pfap2-g and other SRBs after treatment. Estimated parasite age at the time of treatment was negatively correlated with the increase in pfap2-g transcript levels, suggesting that younger parasites are less susceptible to stimulation of sexual conversion., Interpretation: We observed enhanced expression of SRBs after ART-based treatment in many patients, which suggests that in natural malaria infections sexual conversion rates can be altered by treatment. ART-based treatment reduces the potential of a treated individual to transmit the disease, but we hypothesise that under some circumstances this reduction may be attenuated by ART-enhanced sexual conversion., Funding: Spanish Agencia Estatal de Investigación (AEI), European Regional Development Fund (ERDF, European Union), Belgium Development Cooperation (DGD), Canadian University Health Network (UHN), TransGlobalHealth-Erasmus Mundus (European Union)., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The RTS,S/AS01E vaccine targets the circumsporozoite protein (CSP) of the Plasmodium falciparum (P. falciparum) parasite. Protein microarrays were used to measure levels of IgG against 1000 P. falciparum antigens in 2138 infants (age 6-12 weeks) and children (age 5-17 months) from 6 African sites of the phase III trial, sampled before and at 4 longitudinal visits after vaccination. One month postvaccination, IgG responses to 17% of all probed antigens showed differences between RTS,S/AS01E and comparator vaccination groups, whereas no prevaccination differences were found. A small subset of antigens presented IgG levels reaching 4- to 8-fold increases in the RTS,S/AS01E group, comparable in magnitude to anti-CSP IgG levels (~11-fold increase). They were strongly cross-correlated and correlated with anti-CSP levels, waning similarly over time and reincreasing with the booster dose. Such an intriguing phenomenon may be due to cross-reactivity of anti-CSP antibodies with these antigens. RTS,S/AS01E vaccinees with strong off-target IgG responses had an estimated lower clinical malaria incidence after adjusting for age group, site, and postvaccination anti-CSP levels. RTS,S/AS01E-induced IgG may bind strongly not only to CSP, but also to unrelated malaria antigens, and this seems to either confer, or at least be a marker of, increased protection from clinical malaria.

Genetic associations for lipid traits have identified hundreds of variants with clear differences across European, Asian and African studies. Based on a sub-Saharan-African GWAS for lipid traits in the population cross-sectional AWI-Gen cohort (N = 10,603) we report a novel LDL-C association in the GATB region (P-value=1.56 × 10 -8 ). Meta-analysis with four other African cohorts (N = 23,718) provides supporting evidence for the LDL-C association with the GATB/FHIP1A region and identifies a novel triglyceride association signal close to the FHIT gene (P-value =2.66 × 10 -8 ). Our data enable fine-mapping of several well-known lipid-trait loci including LDLR, PMFBP1 and LPA. The transferability of signals detected in two large global studies (GLGC and PAGE) consistently improves with an increase in the size of the African replication cohort. Polygenic risk score analysis shows increased predictive accuracy for LDL-C levels with the narrowing of genetic distance between the discovery dataset and our cohort. Novel discovery is enhanced with the inclusion of African data., (© 2022. The Author(s).)

Atherosclerosis precedes the onset of clinical manifestations of cardiovascular diseases (CVDs). We used carotid intima-media thickness (cIMT) to investigate genetic susceptibility to atherosclerosis in 7894 unrelated adults (3963 women, 3931 men; 40 to 60 years) resident in four sub-Saharan African countries. cIMT was measured by ultrasound and genotyping was performed on the H3Africa SNP Array. Two new African-specific genome-wide significant loci for mean-max cIMT, SIRPA (p = 4.7E-08), and FBXL17 (p = 2.5E-08), were identified. Sex-stratified analysis revealed associations with one male-specific locus, SNX29 (p = 6.3E-09), and two female-specific loci, LARP6 (p = 2.4E-09) and PROK1 (p = 1.0E-08). We replicate previous cIMT associations with different lead SNPs in linkage disequilibrium with SNPs primarily identified in European populations. Our study find significant enrichment for genes involved in oestrogen response from female-specific signals. The genes identified show biological relevance to atherosclerosis and/or CVDs, sex-differences and transferability of signals from non-African studies., (© 2022. The Author(s).)

Objective: To collect context-specific insights into maternal and child health and nutrition issues, and to explore potential solutions in Nanoro, Burkina Faso., Design: Eleven focus groups with men and women from eleven communities, facilitated by local researchers., Setting: The study took place in the Nanoro Health district, in the West-Central part of Burkina Faso., Participants: Eighty-six men (18-55 years) and women by age group: 18-25; 26-34 and 35-55 years, participated in the group discussions., Results: Participants described barriers to optimal nutrition of mothers and children related to a range of community factors, with gender inequality as central. Major themes in the discussions are related to poverty and challenges generated by socially and culturally determined gender roles. Sub-themes are women lacking access to food whilst pregnant and having limited access to health care and opportunities to generate income. Although communities believe that food donations should be implemented to overcome this, they also pointed out the need for enhancing their own food production, requiring improved agricultural technologies. Given the important role that women could play in reducing malnutrition, these communities felt they needed to be empowered to do so and supported by men. They also felt that this had to be carried out in the context of an enhanced health care system., Conclusions: Findings reported here highlight the importance of nutrition-sensitive interventions and women's empowerment in improving maternal and child nutrition. There is a need to integrate a sustainable multi-sectorial approach which goes beyond food support.

Objective: To explore community perceptions on maternal and child nutrition issues in Sub-Saharan Africa., Design: Thirty focus groups with men and women from three communities facilitated by local researchers., Setting: One urban (Soweto, South Africa) and two rural settings (Navrongo, Ghana and Nanoro, Burkina Faso) at different stages of economic transition., Participants: Two hundred thirty-seven men and women aged 18-55 years, mostly subsistence farmers in Navrongo and Nanoro and low income in Soweto., Results: Differences in community concerns about maternal and child health and nutrition reflected the transitional stage of the country. Community priorities revolved around poor nutrition and hunger caused by poverty, lack of economic opportunity and traditional gender roles. Men and women felt they had limited control over food and other resources. Women wanted men to take more responsibility for domestic chores, including food provision, while men wanted more involvement in their families but felt unable to provide for them. Solutions suggested focusing on ways of increasing control over economic production, family life and domestic food supplies. Rural communities sought agricultural support, while the urban community wanted regulation of the food environment., Conclusions: To be acceptable and effective, interventions to improve maternal and child nutrition need to take account of communities' perceptions of their needs and address wider determinants of nutritional status and differences in access to food reflecting the stage of the country's economic transition. Findings suggest that education and knowledge are necessary but not sufficient to support improvements in women's and children's nutritional status.

Background: Half of global child deaths occur in sub-Saharan Africa. Understanding child mortality patterns and risk factors will help inform interventions to reduce this heavy toll. The Nanoro Health and Demographic Surveillance System (HDSS), Burkina Faso was described previously, but patterns and potential drivers of heterogeneity in child mortality in the district had not been studied. Similar studies in other districts indicated proximity to health facilities as a risk factor, usually without distinction between facility types., Methods: Using Nanoro HDSS data from 2009 to 2013, we estimated the association between under-5 mortality and proximity to inpatient and outpatient health facilities, seasonality of death, age group, and standard demographic risk factors., Results: Living in homes 40-60 min and > 60 min travel time from an inpatient facility was associated with 1.52 (95% CI: 1.13-2.06) and 1.74 (95% CI: 1.27-2.40) greater hazard of under-5 mortality, respectively, than living in homes < 20 min from an inpatient facility. No such association was found for outpatient facilities. The wet season (July-November) was associated with 1.28 (95% CI: 1.07, 1.53) higher under-5 mortality than the dry season (December-June), likely reflecting the malaria season., Conclusions: Our results emphasize the importance of geographical proximity to health care, distinguish between inpatient and outpatient facilities, and also show a seasonal effect, probably driven by malaria., (© 2021. The Author(s).)

Background: Substance misuse is a global public health problem. In addition to social and economic concerns, consumption of tobacco and alcohol is associated with susceptibility to cardiovascular, respiratory, and infectious diseases, cancers, and risk of transition to substance use disorders. African data suggest regional differences in the prevalence and patterns of substance use, but a number of key questions remain. This cross-sectional population-based study of middle-aged adults aims to examine prevalence and socio-demographic correlates of substance use in four sub-Saharan African countries, in rural and urban settings., Methods: Participants aged between 40 and 60 years were recruited from six research centres as part of the Africa Wits-INDEPTH partnership for Genomic Research study. Data on patterns of tobacco and alcohol consumption was captured, and the latter further assessed using the CAGE (cut-annoyed-guilty-eye) questionnaire., Results: Data from 10,703 participants suggested that more men (68.4%) than women (33.3%) were current substance users. The prevalence of current smoking was significantly higher in men than in women (34.5% vs 2.1%, p < 0.001). Smokeless tobacco was used more by women than men (14.4% vs 5.3%, p < 0.001). Current smoking was associated with alcohol consumption in men, and smoking cessation in men was associated with being a former drinker, having higher socio-economic status, and if married or cohabiting. Current alcohol consumption was higher in men, compared to women (60.3% vs 29.3%), and highest in men from Soweto (70.8%) and women from Nanoro (59.8%). The overall prevalence of problematic alcohol consumption among men was 18.9%, and women 7.3%. Men were significantly more likely to develop problematic drinking patterns, and this was more common in those who were divorced or widowed, and in current smokers., Conclusions: Regional variation in the patterns and prevalence of substance use was observed across study sites, and in rural and urban settings. The high levels of substance use recorded in this study are of concern due to the increased risk of associated morbidities. Further longitudinal data will be valuable in determining trends in substance misuse in Africa.

Introduction: from a genetic point of view P. falciparumis extremely polymorphic. There is a variety of parasite strains infesting individuals living in malaria endemic areas. The purpose of this study is to investigate the relationship between polymorphisms in Plasmodium falciparum parasites and Pfcrt and Pfmdr1 gene mutations in Nanoro area, Burkina Faso., Methods: blood samples from plasmodium carriers residing in the Nanoro Health District were genotyped using nested PCR. Parasite gene mutations associated with resistance to antimalarial drugs were detected by PCR-RFLP., Results: samples of 672 patients were successfully genotyped. No msp1and msp2allelic families exhibited an increase in developing mutations in resistance genes. However, mutant strains of these genes were present at greater levels in monoclonal infections than in multi-clonal infections., Conclusion: this study provides an overview of the relationship between polymorphisms in Plasmodium falciparum parasites and mutations in resistance genes. These data will undoubtedly contribute to improving knowledge of the parasite´s biology and its mechanisms of resistance to antimalarial drugs., Competing Interests: Les auteurs ne déclarent aucun conflit d´intérêts., (Copyright: Paul Sondo et al.)

Background: Malaria and malnutrition represent major public health concerns worldwide especially in Sub-Sahara Africa. Despite implementation of seasonal malaria chemoprophylaxis (SMC), an intervention aimed at reducing malaria incidence among children aged 3-59 months, the burden of malaria and associated mortality among children below age 5 years remains high in Burkina Faso. Malnutrition, in particular micronutrient deficiency, appears to be one of the potential factors that can negatively affect the effectiveness of SMC. Treating micronutrient deficiencies is known to reduce the incidence of malaria in highly prevalent malaria zone such as rural settings. Therefore, we hypothesized that a combined strategy of SMC together with a daily oral nutrients supplement will enhance the immune response and decrease the incidence of malaria and malnutrition among children under SMC coverage., Methods: Children (6-59 months) under SMC coverage receiving vitamin A supplementation will be randomly assigned to one of the three study arms (a) SMC + vitamin A alone, (b) SMC + vitamin A + zinc, or (c) SMC + vitamin A + Plumpy'Doz™ using 1:1:1 allocation ratio. After each SMC monthly distribution, children will be visited at home to confirm drug administration and followed-up for 1 year. Anthropometric indicators will be recorded at each visit and blood samples will be collected for microscopy slides, haemoglobin measurement, and spotted onto filter paper for further PCR analyses. The primary outcome measure is the incidence of malaria in each arm. Secondary outcome measures will include mid-upper arm circumference and weight gain from baseline measurements, coverage and compliance to SMC, occurrence of adverse events (AEs), and prevalence of molecular markers of antimalarial resistance comprising Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps., Discussion: This study will demonstrate an integrated strategy of malaria and malnutrition programmes in order to mutualize resources for best impact. By relying on existing strategies, the policy implementation of this joint intervention will be scalable at country and regional levels., Trial Registration: ClinicalTrials.gov NCT04238845 . Registered on 23 January 2020 https://clinicaltrials.gov/ct2/show/NCT04238845.

Background: Stalled progress in controlling Plasmodium falciparum malaria highlights the need for an effective and deployable vaccine. RTS,S/AS01, the most effective malaria vaccine candidate to date, demonstrated 56% efficacy over 12 months in African children. We therefore assessed a new candidate vaccine for safety and efficacy., Methods: In this double-blind, randomised, controlled, phase 2b trial, the low-dose circumsporozoite protein-based vaccine R21, with two different doses of adjuvant Matrix-M (MM), was given to children aged 5-17 months in Nanoro, Burkina Faso-a highly seasonal malaria transmission setting. Three vaccinations were administered at 4-week intervals before the malaria season, with a fourth dose 1 year later. All vaccines were administered intramuscularly into the thigh. Group 1 received 5 μg R21 plus 25 μg MM, group 2 received 5 μg R21 plus 50 μg MM, and group 3, the control group, received rabies vaccinations. Children were randomly assigned (1:1:1) to groups 1-3. An independent statistician generated a random allocation list, using block randomisation with variable block sizes, which was used to assign participants. Participants, their families, and the local study team were all masked to group allocation. Only the pharmacists preparing the vaccine were unmasked to group allocation. Vaccine safety, immunogenicity, and efficacy were evaluated over 1 year. The primary objective assessed protective efficacy of R21 plus MM (R21/MM) from 14 days after the third vaccination to 6 months. Primary analyses of vaccine efficacy were based on a modified intention-to-treat population, which included all participants who received three vaccinations, allowing for inclusion of participants who received the wrong vaccine at any timepoint. This trial is registered with ClinicalTrials.gov, NCT03896724., Findings: From May 7 to June 13, 2019, 498 children aged 5-17 months were screened, and 48 were excluded. 450 children were enrolled and received at least one vaccination. 150 children were allocated to group 1, 150 children were allocated to group 2, and 150 children were allocated to group 3. The final vaccination of the primary series was administered on Aug 7, 2019. R21/MM had a favourable safety profile and was well tolerated. The majority of adverse events were mild, with the most common event being fever. None of the seven serious adverse events were attributed to the vaccine. At the 6-month primary efficacy analysis, 43 (29%) of 146 participants in group 1, 38 (26%) of 146 participants in group 2, and 105 (71%) of 147 participants in group 3 developed clinical malaria. Vaccine efficacy was 74% (95% CI 63-82) in group 1 and 77% (67-84) in group 2 at 6 months. At 1 year, vaccine efficacy remained high, at 77% (67-84) in group 1. Participants vaccinated with R21/MM showed high titres of malaria-specific anti-Asn-Ala-Asn-Pro (NANP) antibodies 28 days after the third vaccination, which were almost doubled with the higher adjuvant dose. Titres waned but were boosted to levels similar to peak titres after the primary series of vaccinations after a fourth dose administered 1 year later., Interpretation: R21/MM appears safe and very immunogenic in African children, and shows promising high-level efficacy., Funding: The European & Developing Countries Clinical Trials Partnership, Wellcome Trust, and National Institute for Health Research Oxford Biomedical Research Centre., Competing Interests: Declaration of interests AVSH and KJE are named as coinventors on patent applications related to R21. GG, LF, and JR are employees of Novavax, developers of the MM adjuvant, and US is an employee of the Serum Institute of India, codeveloper of the R21/MM vaccine. The other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)