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Haffsatou Sawadogo,1,2 Issiaka Soulama,3,4 Adama Zida,2,5 Cheikna Zongo,1 Patindoilba Marcel Sawadogo,2,5 Kiswendsida Thierry Guiguemde,5,6 Seni Nikiema,7 Salimata Emilie Badoum,1,8 Salam Sawadogo,7 Aïcha Tou,4 Salif Sombié,4 Chanolle Tchekounou,1,9 Sindié Samuel Sermé,1,8 Rasmata Ouedraogo-Traoré,9 Tinga Robert Guiguemdé,10 Aly Savadogo1 1Laboratory of Applied Biochemistry and Immunology (LABIA), Joseph KI - ZERBO University, Ouagadougou, Burkina Faso; 2Parasitology-Mycology Department, Centre Hospitalier Universitaire Yalgado Ouédraogo (CHU-YO), Ouagadougou, Burkina Faso; 3Health Science Research Institute (IRSS), Ouagadougou, Burkina Faso; 4National Malaria Research and Training Center (CNRFP), Ouagadougou, Burkina Faso; 5Health Sciences Training and Research Unit (UFR/SDS), Joseph KI - ZERBO University, Ouagadougou, Burkina Faso; 6Centre Hospitalier Universitaire Pédiatrique – Charles de Gaulle (CHU-CDG), Ouagadougou, Burkina Faso; 7Molecular Biology and Genetics Laboratory (LABIOGENE), Joseph KI - ZERBO University, Ouagadougou, Burkina Faso; 8Health Action Research Group (GRAS), Ouagadougou, Burkina Faso; 9International Institute of Science and Technology (Iistech), Ouagadougou, Burkina Faso; 10Parasitology-Mycology Laboratory, National Institute of Health Sciences (INSP), Nazi Boni University, Bobo-Dioulasso, Burkina FasoCorrespondence: Cheikna Zongo, Laboratory of Applied Biochemistry and Immunology (LABIA), Joseph KI - ZERBO University, Burkina Faso 03 BP 7021 Ouagadougou 03, Ouagadougou, Burkina Faso, Tel +226 76579605, Fax +226 25307242, Email Cheikna.zongo@ujkz.bfPurpose: Intermittent preventive treatment with sulfadoxine-pyrimethamine is widely used for the prevention of malaria in pregnant women in Africa. Known resistance cases of sulfadoxine-pyrimethamine during pregnancy need to be follow up to support IPTp implementation in Burkina Faso. However, data on the development and spread of resistance to this molecule are lacking. This study aimed to investigating the genetic diversity of P. falciparum and the mutation prevalence in the dhfr and dhps genes infected from postpartum infected placentas.Patients and Methods: This was a prospective and cross-sectional study conducted between April 2019 and March 2020 in four health districts of Ouagadougou capital city. From the placentas collected after delivery, P. falciparum detection and mps1 and msp2 polymorphism analysis were performed by nested PCR. The resistance profile was checked after analyzing the mutation point on dhfr and dhps genes.Results: PCR-positive samples were estimated at 96% for msp1 and 98% for msp2. The polymorphism analysis showed that the RO33 and 3D7 allelic families were the most widespread with 62.5% and 91.83%, respectively. Multiple infections by msp1 and msp2 were frequent with 12.50% and 92.92%, respectively. The prevalence of individual dhfr mutation point, 51I, 108A, and 59R, was 1.96, 15.68, and 7.84, respectively, and the dhps mutation point, 437G, was 3.92. There is no detected mutation at the point 164L and 540E. The triple (51I+108A+59R) in dhfr and quadruple (51I+108A+59R+ 437G) mutation were not found.Conclusion: The results showed that Plasmodium falciparum has a high genetic diversity of msp1 and msp2. This suggests that dhfr and dhps mutant genotypes are potential early warning factors in the increase in the sulfadoxine-pyrimethamine resistance.Keywords: sulfadoxine-pyrimethamine, Plasmodium falciparum, msp1, msp2, dhfr, dhps, placenta

Séni Nikiema,1,2 Issiaka Soulama,1,3 Salif Sombié,1 André-Marie Tchouatieu,4 Samuel Sindie Sermé,5 Noëlie Béré Henry,5 Nicolas Ouedraogo,1 Nathalie Ouaré,1,6 Raissa Ily,1,6 Oumarou Ouédraogo,3 Dramane Zongo,3 Florencia Wendkuuni Djigma,2 Alfred B Tiono,1 Sodiomon B Sirima,5 Jacques Simporé2,7 1Research Department, Centre National de Recherche et de Formation sur le Paludisme (CNRFP)/Institut National de Santé Publique (INSP), Ouagadougou, Burkina Faso; 2Laboratoire de Biologie Moléculaire et de Génétique (LABIOGENE), Université Joseph KI-ZERBO, Ouagadougou, Burkina Faso; 3Biomedical and Public Health Department, Institut de Recherche en Sciences de la Santé (IRSS)/Centre National de Recherche Scientifiques et Technologiques (CNRST), Ouagadougou, Burkina Faso; 4Access and Product Management – Chemoprevention Department, Medicines for Malaria Venture (MMV), Geneva, Switzerland; 5Direction Scientifique, Groupe de Recherche Action en Santé, Ouagadougou, Burkina Faso; 6Institut Supérieur des Sciences de la santé (IN.S.SA), Université Nazi Boni, Bobo Dioulasso, Burkina Faso; 7Centre de recherche biomoléculaire Pietro Annigoni (CERBA), Ouagadougou, Burkina FasoCorrespondence: Issiaka Soulama, Institut de Recherche en Sciences de la Santé /CNRST, 06 BP 9067, Ouagadougou, Burkina Faso, Tel +22670757190, Email iss.soulama@gmail.comAbstract: Seasonal Malaria Chemoprevention (SMC), which combines amodiaquine (AQ) with sulfadoxine-pyrimethamine (SP), is an effective and promising strategy, recommended by WHO, for controlling malaria morbidity and mortality in areas of intense seasonal transmission. Despite the effectiveness of this strategy, a number of controversies regarding the impact of the development of malaria-specific immunity and challenges of the strategy in the context of increasing and expanding antimalarial drugs resistance but also the limited coverage of the SMC in children make the relevance of the SMC questionable, especially in view of the financial and logistical investments. Indeed, the number of malaria cases in the target group, children under 5 years old, has increased while the implementation of SMC is been extended in several African countries. This ambivalence of the SMC strategy, the increase in the prevalence of malaria cases suggests the need to evaluate the SMC and understand some of the factors that may hinder the success of this strategy in the implementation areas. The present review discusses the impact of the SMC on malaria morbidity, parasite resistance to antimalarial drugs, molecular and the immunity affecting the incidence of malaria in children. This approach will contribute to improving the malaria control strategy in highly seasonal transmission areas where the SMC is implemented.Keywords: seasonal malaria chemoprevention, immunity, resistance, sulfadoxine-pyrimethamine, amodiaquine

Introduction: Malaria still remains the most frequent parasitic disease on the world with, in 2022, 249 million cases and 608,000 deaths worldwide. Malaria control is compromised by the spread of the parasite's resistance to available antimalarials. The objective of our study is to characterize the Plasmodium falciparum resistance genes to common antimalarial drugs in semi-urban areas of Burkina Faso., Materials and Methods: This is a prospective cross-sectional study whose collection took place from June to October 2021 and from June to October 2022 in five health facilities in Burkina Faso. The molecular analysis based on PCR-RFLP took place from January to June 2023 at Centre National de Recherche et de Formation (CNRFP) to determine resistance genes such as Pfcrt, Pfmdr1, Pfdhps, and Pfdhfr., Results: A total of 150 samples were analyzed giving a prevalence of 46.67, 1.33, 0.67, 20, 82, and 4.67%, for Pfcrt 76 T, Pfmdr1 86Y, Pfdhps 437G, Pfdhfr 51I, Pfdhfr 59R, and Pfdhfr 108N mutations, respectively. There are no mutations observed Pfdhps 540E and Pfdhfr 164L positions. However, mutation on Pfdhfr 59R position was the most common. In addition, triple mutation (Pfdhps 437G + Pfdhfr 59R + Pfdhfr 108N) was found with a low frequency which is 0.67%., Conclusion: Surveillance of Plasmodium falciparum resistance markers to antimalarial drugs, remains one of the priorities in the context of the control or malaria elimination., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Antimalarial drugs that can block the transmission of Plasmodium gametocytes to mosquito vectors would be highly beneficial for malaria elimination efforts. Identifying transmission-blocking drugs currently relies on evaluation of their activity against gametocyte-producing laboratory parasite strains and would benefit from a testing pipeline with genetically diverse field isolates. The aims of this study were to develop a pipeline to test drugs against P. falciparum gametocyte field isolates and to evaluate the transmission-blocking activity of a set of novel compounds. Two assays were designed so they could identify both the overall transmission-blocking activity of a number of marketed and experimental drugs by direct membrane feeding assays (DMFA), and then also discriminate between those that are active against the gametocytes (gametocyte killing or sterilizing) or those that block development in the mosquito (sporontocidal). These DMFA assays used venous blood samples from naturally infected Plasmodium falciparum gametocyte carriers and locally reared Anopheles gambiae s.s. mosquitoes. Overall transmission-blocking activity was assessed following a 24 hour incubation of compound with gametocyte infected blood (TB-DMFA). Sporontocidal activity was evaluated following addition of compound directly prior to feeding, without incubation (SPORO-DMFA); Gametocyte viability was retained during 24-hour incubation at 37°C when gametocyte infected red blood cells were reconstituted in RPMI/serum. Methylene-blue, MMV693183, DDD107498, atovaquone and P218 showed potent transmission-blocking activity in the TB-DMFA, and both atovaquone and the novel antifolate P218 were potent inhibitors of sporogonic development in the SPORO-DMA. This work establishes a pipeline for the integral use of field isolates to assess the transmission-blocking capacity of antimalarial drugs to block transmission that should be validated in future studies., Competing Interests: No, the authors have declared that no competing interests exist., (Copyright: © 2023 B. Henry 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.)

The regulation of immune cell responses to infection is a complex process that involves various molecular mechanisms, including epigenetic regulation. DNA methylation has been shown to play central roles in regulating gene expression and modulating cell response during infection. However, the nature and extent to which DNA methylation is involved in the host immune response in human malaria remains largely unknown. Here, we present a longitudinal study investigating the temporal dynamics of genome-wide in vivo DNA methylation profiles using 189 MethylationEPIC 850 K profiles from 66 children in Burkina Faso, West Africa, sampled three times: before infection, during symptomatic parasitemia, and after malaria treatment. The results revealed major changes in the DNA methylation profiles of children in response to both Plasmodium falciparum infection and malaria treatment, with widespread hypomethylation of CpGs upon infection (82% of 6.8 K differentially methylated regions). We document a remarkable reversal of CpG methylation profiles upon treatment to pre-infection states. These changes implicate divergence in core immune processes, including the regulation of lymphocyte, neutrophil, and myeloid leukocyte function. Integrative DNA methylation-mRNA analysis of a top differentially methylated region overlapping the pro-inflammatory gene TNF implicates DNA methylation of TNF cis regulatory elements in the molecular mechanisms of TNF regulation in human malaria. Our results highlight a central role of epigenetic regulation in mounting the host immune response to P. falciparum infection and in response to malaria treatment., 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., (Copyright © 2023 Almojil, Diawara, Soulama, Dieng, Manikandan, Sermé, Sombié, Diarra, Barry, Coulibaly, Sirima and Idaghdour.)

Background: The current paper examines the level of use of evidence and factors affecting the use of evidence by frontline maternal, newborn and child health (MNCH) and reproductive and child health (RCH) staff in practice decisions in selected health facilities in Ghana., Methods: Data on use of evidence and its correlates was collected from 509 frontline healthcare staff drawn from 44 health facilities in three regions in Ghana. Means were used to examine the level of use of evidence, whiles cross-tabulations and Partial Least Squares-based regression were used to examine factors associated with the use of evidence in practice decisions by frontline MNCH/RCH staff., Findings: The findings suggest a high level of use of evidence by frontline MNCH/RCH staff in practice decisions (score of 3.98 out of 5), albeit that evidence use is skewed towards the use of practice guidelines and policies. For the antecedents of evidence use, attitude had the highest score (3.99), followed by knowledge (3.8), access to evidence (3.77) and organizational structure (3.57), using a threshold of 5. The regression results indicate that attitudes and knowledge of frontline MNCH/RCH staff, organizational structure (strongest association), years of experience, being a male and working in a mission health facility are significantly positive correlated with evidence use, whiles working in a private health facility or in the post-natal clinic is negatively correlated with the use of evidence., Conclusion: We argue that any effort to improve the use of evidence by frontline MNCH/RCH staff in practice decisions should focus on improving attitudes and knowledge of staff as well as challenges related to the structure of the organisation. Given however that the score for attitude was relatively high, emphases to improve evidence use should be on access to evidence and organizational structure in particular, which had the lowest score even though it has the strongest association with the use of evidence., (© 2022. The Author(s).)

Background: Malaria in pregnancy remains a public health problem in sub-Saharan Africa. Identifying risk factors for malaria in pregnancy could assist in developing interventions to reduce the risk of malaria in Burkina Faso and other countries in the region., Methods: Two cross-sectional surveys were carried out to measure Plasmodium falciparum infection using microscopy in pregnant women in Saponé Health District, central Burkina Faso. Data were collected on individual, household and environmental variables and their association with P. falciparum infection assessed using multivariable analysis., Results: A total of 356 pregnant women were enrolled in the surveys, 174 during the dry season and 182 during the wet season. The mean number of doses of sulfadoxine-pyrimethamine for Intermittent Preventive Treatment in pregnancy (IPTp-SP) was 0.4 doses during the first trimester, 1.1 doses at the second and 2.3 doses at the third. Overall prevalence of P. falciparum infection by microscopy was 15.7%; 17.8% in the dry season and 13.7% in the wet season. 88.2% of pregnant women reported sleeping under an insecticide-treated net (ITN) on the previous night. The odds of P. falciparum infection was 65% lower in women who reported using an ITN compared to those that did not use an ITN (Odds ratio, OR = 0.35, 95% CI 0.14-0.86, p = 0.02). IPTp-SP was also associated with reduced P. falciparum infection, with each additional dose of IPTp-SP reducing the odds of infection by 44% (OR = 0.56, 95% CI 0.39-0.79, p = 0.001). Literate women had a 2.54 times higher odds of P. falciparum infection compared to illiterate women (95% CI 1.31-4.91, p = 0.006)., Conclusions: The prevalence of P. falciparum infection among pregnant women remains high in Burkina Faso, although use of IPTp-SP and ITNs were found to reduce the odds of infection. Despite this, compliance with IPTp-SP remains far from that recommended by the National Malaria Control Programme and World Health Organization. Behaviour change communication should be strengthened to encourage compliance with protective malaria control tools during pregnancy., (© 2021. The Author(s).)

Host responses to infection with the malaria parasite Plasmodium falciparum vary among individuals for reasons that are poorly understood. Here we reveal metabolic perturbations as a consequence of malaria infection in children and identify an immunosuppressive role of endogenous steroid production in the context of P. falciparum infection. We perform metabolomics on matched samples from children from two ethnic groups in West Africa, before and after infection with seasonal malaria. Analysing 306 global metabolomes, we identify 92 parasitaemia-associated metabolites with impact on the host adaptive immune response. Integrative metabolomic and transcriptomic analyses, and causal mediation and moderation analyses, reveal an infection-driven immunosuppressive role of parasitaemia-associated pregnenolone steroids on lymphocyte function and the expression of key immunoregulatory lymphocyte genes in the Gouin ethnic group. In children from the less malaria-susceptible Fulani ethnic group, we observe opposing responses following infection, consistent with the immunosuppressive role of endogenous steroids in malaria. These findings advance our understanding of P. falciparum pathogenesis in humans and identify potential new targets for antimalarial therapeutic interventions., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The world continues to battle the ongoing COVID-19 pandemic. Whereas many countries are currently experiencing the second wave of the outbreak; Africa, despite being the last continent to be affected by the virus, has not experienced as much devastation as other continents. For example, West Africa, with a population of 367 million people, had confirmed 412 178 cases of COVID-19 with 5363 deaths as of 14 March 2021; compared with the USA which had recorded almost 30 million cases and 530 000 deaths, despite having a slightly smaller population (328 million). Several postulations have been made in an attempt to explain this phenomenon. One hypothesis is that African countries have leveraged on experiences from past epidemics to build resilience and response strategies which may be contributing to protecting the continent's health systems from being overwhelmed. This practice paper from the West African Health Organization presents experience and data from the field on how countries in the region mobilised support to address the pandemic in the first year, leveraging on systems, infrastructure, capacities developed and experiences from the 2014 Ebola virus disease outbreak., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The mechanisms behind the ability of Plasmodium falciparum to evade host immune system are poorly understood and are a major roadblock in achieving malaria elimination. Here, we use integrative genomic profiling and a longitudinal pediatric cohort in Burkina Faso to demonstrate the role of post-transcriptional regulation in host immune response in malaria. We report a strong signature of miRNA expression differentiation associated with P. falciparum infection (127 out of 320 miRNAs, B-H FDR 5%) and parasitemia (72 miRNAs, B-H FDR 5%). Integrative miRNA-mRNA analysis implicates several infection-responsive miRNAs (e.g., miR-16-5p, miR-15a-5p and miR-181c-5p) promoting lymphocyte cell death. miRNA cis-eQTL analysis using whole-genome sequencing data identified 1,376 genetic variants associated with the expression of 34 miRNAs (B-H FDR 5%). We report a protective effect of rs114136945 minor allele on parasitemia mediated through miR-598-3p expression. These results highlight the impact of post-transcriptional regulation, immune cell death processes and host genetic regulatory control in malaria.

While significant advances have been made in understanding Plasmodium falciparum gametocyte biology and its relationship with malaria parasite transmission, the gametocyte sex ratio contribution to this process still remains a relevant research question. The present review discusses the biology of sex determination in P. falciparum, the underlying host and parasite factors, the sex specific susceptibility to drugs, the effect of sex ratio dynamics on malaria parasite transmission and the development of gametocyte sex specific diagnosis tools. Despite the inherent differences across several studies and approaches, the emerging picture highlights a potentially relevant contribution of the P. falciparum gametocyte sex ratio in the modulation of malaria parasite transmission. The increasing availability of molecular methods to measure gametocyte sex ratio will enable evaluation of important parameters, such as the impact of drug treatment on gametocyte sex ratio in vitro and in vivo as well as the changes of gametocyte sex ratios in natural infections, key steps towards elucidating how these parameters affect parasite infectiousness to the mosquito vectors.

Background: The paper carries out a situational analysis to examine the production, dissemination and utilisation of reproductive and child health-related evidence to inform policy formulation in Ghana's health sector., Methods: The study used Wald's model of knowledge production, transfer and utilisation as a conceptual model to collect relevant data via interviews and administration of questionnaire to a network of persons who either previously or currently hold policy-relevant positions in Ghana's health sector. Additional data was also gathered through a scoping review of the knowledge transfer and research utilisation literature, existing reproductive and child health policies, protocols and guidelines and information available on the websites of relevant institutions in Ghana's health sector., Results: The findings of the study suggest that the health sector in Ghana has major strengths (strong knowledge production capacity, a positive environment for the promotion of evidence-informed policy) and opportunities (access to major donors who have the resources to fund good quality research and access to both local and international networks for collaborative research). What remains a challenge, however, is the absence of a robust institutional-wide mechanism for collating research needs and communicating these to researchers, communicating research findings in forms that are friendlier to policy-makers and the inability to incorporate funding for research into the budget of the health sector., Conclusion: The study concludes, admonishing the Ministry of Health and its agencies to leverage on the existing strengths and opportunities to address the identified challenges.