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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