Cross-reactivity of rPvs48/45, a recombinant Plasmodium vivax protein, with sera from Plasmodium falciparum endemic areas of Africa.

Background: Ps48/45, a Plasmodium gametocyte surface protein, is a promising candidate for malaria transmission-blocking (TB) vaccine. Due to its relevance for a multispecies vaccine, we explored the cross-reactivity and TB activity of a recombinant P. vivax Ps48/45 protein (rPvs48/45) with sera from P. falciparum-exposed African donors. Methods: rPvs48/45 was produced in Chinese hamster ovary cell lines and tested by ELISA for its cross-reactivity with sera from Burkina Faso, Tanzania, Mali, and Nigeria - In addition, BALB/c mice were immunized with the rPvs48/45 protein formulated in Montanide ISA-51 and inoculated with a crude extract of P. falciparum NF-54 gametocytes to evaluate the parasite-boosting effect on rPvs48/45 antibody titers. Specific anti-rPvs48/45 IgG purified from African sera was used to evaluate the ex vivo TB activity on P. falciparum, using standard mosquito membrane feeding assays (SMFA). Results: rPvs48/45 protein showed cross-reactivity with sera of individuals from all four African countries, in proportions ranging from 94% (Tanzania) to 40% (Nigeria). Also, the level of cross-reactive antibodies varied significantly between countries (p<0.0001), with a higher antibody level in Mali and the lowest in Nigeria. In addition, antibody levels were higher in adults (≥ 17 years) than young children (≤ 5 years) in both Mali and Tanzania, with a higher proportion of responders in adults (90%) than in children (61%) (p<0.0001) in Mali, where male (75%) and female (80%) displayed similar antibody responses. Furthermore, immunization of mice with P. falciparum gametocytes boosted anti-Pvs48/45 antibody responses, recognizing P. falciparum gametocytes in indirect immunofluorescence antibody test. Notably, rPvs48/45 affinity-purified African IgG exhibited a TB activity of 61% against P. falciparum in SMFA. Conclusion: African sera (exposed only to P. falciparum) cross-recognized the rPvs48/45 protein. This, together with the functional activity of IgG, warrants further studies for the potential development of a P. vivax and P. falciparum cross-protective TB vaccine.

Seasonal Malaria Chemoprevention Therapy in Children Up To 9 Years of Age: Protocol for a Cluster-Randomized Trial Study.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is recommended by the World Health Organization for the sub-Sahel region in sub-Saharan Africa for preventing malaria in children 3 months old to younger than 5 years. Since 2016, the Malian National Malaria Control Program has deployed SMC countrywide during its high malaria transmission season at a rate of 4 monthly cycles annually. The standard SMC regimen includes sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ). Resistance against SP is suspected to be rising across West Africa; therefore, assessing the effectiveness of an alternative antimalarial drug for SMC is needed to provide a second-line regimen when it is ultimately needed. It is not well understood whether SMC effectively prevents malaria in children aged 5 years or older. OBJECTIVE: The primary goal of the study is to compare 2 SMC regimens (SP-AQ and dihydroartemisinin-piperaquine [DHA-PQ]) in preventing uncomplicated Plasmodium falciparum malaria in children 3 months to 9 years old. Secondly, we will assess the possible use of DHA-PQ as an alternative SMC drug in areas where resistance to SP or AQ may increase following intensive use. METHODS: The study design is a 3-arm cluster-randomized design comparing the SP-AQ and DHA-PQ arms in 2 age groups (younger than 5 years and 5-9 years) and a control group for children aged 5-9 years. Standard SMC (SP-AQ) for children younger than 5 years was provided to the control arm, while SMC with SP-AQ was delivered to children aged 3 months to 9 years (arm 2), and SMC with DHA-PQ will be implemented in study arm 3 for children up to 9 years of age. The study was performed in Mali's Koulikoro District, a rural area in southwest Mali with historically high malaria transmission rates. The study's primary outcome is P falciparum incidence for 2 SMC regimens in children up to 9 years of age. Should DHA-PQ provide an acceptable alternative to SP-AQ, a plausible second-line prevention option would be available in the event of SP resistance or drug supply shortages. A significant byproduct of this effort included bolstering district health information systems for rapid identification of severe malaria cases. RESULTS: The study began on July 1, 2019. Through November 2022, a total of 4556 children 3 months old to younger than 5 years were enrolled. Data collection ended in spring 2023, and the findings are expected to be published later in early 2024. CONCLUSIONS: Routine evaluation of antimalarial drugs is needed to establish appropriate SMC age targets. The study goals here may impact public health policy and provide alternative therapies in the event of drug shortages or resistance. TRIAL REGISTRATION: ClinicalTrials.gov NCT04149106, https://clinicaltrials.gov/ct2/show/NCT04149106. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51660.

Modeling clinical malaria episodes in different ecological settings in Mali, 2018-2022.

Objectives: Following the scaling-up of malaria control strategies in Mali, understanding the changes in age-specific prevalence of infection and risk factors associated with remains necessary to determine new priorities to progress toward disease elimination. This study aimed to estimate the risk of clinical malaria using longitudinal data across three different transmission settings in Mali. Methods: Cohort-based longitudinal studies were performed from April 2018 to December 2022. Incidence of malaria was measured through community health center-based passive case detection. Generalized estimation equation model was used to assess risk factors for clinical malaria. Results: A total of 21,453 clinical presentations were reported from 4500 participants, mainly from July to November. Data shows a significant association between malaria episodes, sex, age group, season, and year. Women had lower risk, the risk of clinical episode increased with age up to 14 years then declined, and in both sites, the dry-season risk of clinical episode was significantly lower compared to the rainy season. Conclusion: Determining factors associated with the occurrence of clinical malaria across different ecological settings across the country could help in the development of new strategies aiming to accelerate malaria elimination in an area where malaria transmission remains intense.

Comparing vaccination coverage before and during COVID-19 pandemic in children under one year in the health district of commune V in Bamako, Mali.

INTRODUCTION: Although an essential frontline service in the prevention of child morbidity and mortality, there are indications that routine vaccinations have been disrupted during the COVID-19 pandemic. The present study aimed to compare vaccination coverage before COVID-19 in Mali in 2019 and during COVID-19 in 2020. OBJECTIVE: To compare vaccination coverages before COVID-19 in Mali in 2019 and during COVID-19 in 2020. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: We collected routine immunization data from 2019 to 2020 of children under one year in the health district of Commune V in Bamako which includes twelve community health centers (CSCom). RESULTS: Considering all vaccines together, coverage in 2019 was higher than in 2020 (88.7% vs. 71,6%) (p < 10- 3, Fig. 1). In 2020, low proportions of children vaccinated were observed in May (51.1%) two months after the first COVID-19 case in Mali on March 25, 2020. For all vaccines, the mean number of children vaccinated was significantly higher in 2019 (before COVID-19) as compared to 2020 (during COVID-19) (p < 0.05). However, in September and October 2019 BCG vaccine coverage was lower in 2019 as compared to 2020 (p < 10- 3). CONCLUSION: COVID-19 pandemic has affected routine childhood vaccine coverage in Commune V of Bamako, particularly in May 2020. Therefore, new strategies are needed to improve vaccine coverage in young children below 1.

Prognostics of multiple malaria episodes and nutritional status in children aged 6 to 59 months from 2013 to 2017 in Dangassa, Mali.

Background: In Africa, the relationship between nutritional status and malaria remains complex and difficult to interpret in children. Understanding it is important in the development of malaria control strategies. This study evaluated the effect of nutritional status on the occurrence of multiple malaria episodes in children aged 6 to 59 months between 2013 and 2017 living in the village of Dangassa, Mali. Methods: A community-based longitudinal study was conducted using cross-sectional surveys (SSCs) at the beginning (June) and end (November) of the malaria transmission season associated with passive case detection (PCD) at the Dangassa Community Health Center. Children with asymptomatic malaria infection during cross-sectional surveys were selected and their malaria episodes followed by PCD. Palustrine indicators in person-months were estimated using an ordinal-logistic model repeated on subjects during follow-up periods. Results: The incidence rate (IR) during the period of high transmission (June to October), for 1 episode and for 2 + episodes peaked in 2013 with 65 children (IR = 95.73 per 1000 person-months) and 24 cases (IR = 35.35 per 1000 person-months), respectively. As expected, the risk of multiple episodes occurring during the period of high transmission was 3.23 compared to the period of low transmission after adjusting for other model parameters (95% CI = [2.45-4.26], p = 0.000). Children with anemia were at high risk of having multiple episodes (OR = 1.6, 95% CI [1.12-2.30], p = 0.011). However, the risk of having 2 + episodes for anemic children was higher during the period of low transmission (RR = 1.67, 95% CI [1.15-2.42], p = 0.007) compared to the period of high transmission (RR = 1.58, 95% CI [1.09-2.29], p = 0.016). The trend indicated that anemic and underweight children were significantly associated with multiple malaria episodes during the period of low transmission (p < = 0.001). Conclusion: Our results indicate that multiple episodes of malaria are significantly related to the nutritional status (anemia and underweight) of the child during the two transmission seasons and more pronounced during the dry season (period of low transmission). Further research including other malnutrition parameters will be needed to confirm our findings.

ESBL and carbapenemase-producing Enterobacteriaceae in infectious pleural effusions: current epidemiology at Hôpital du Mali.

Background: Antimicrobial resistance (AMR) is a global health concern, with extended-spectrum ß-lactamases (ESBLs) and carbapenemases being major contributors. Pleural infection (PI) is a severe condition in West Africa, complicated by AMR. This study aimed to investigate the prevalence and molecular characteristics of ESBL and carbapenemase-producing enterobacteria in pleural effusions in Mali. Materials and methods: Pleural fluid samples from 526 patients with pleuritis were analyzed. Enterobacterial species were isolated and identified, and the prevalence of resistance genes (blaOXA-48, blaNDM-1, blaKPC, blaTEM, blaSHV) and virulence factors was determined. Results: Among the patients, 110 were diagnosed with enterobacterial pleuritis. Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were the main pathogens identified. Resistance to ß-lactams and cephalosporins was high, while carbapenems showed good activity. ESBL production was detected in 33.6% of isolates, with blaTEM being the most common gene. Carbapenemase gene (blaNDM-1) was found in three isolates. Conclusion: The study highlights the high prevalence of multidrug-resistant bacteria and the need for appropriate antibiotic selection based on local resistance patterns. Understanding the molecular characteristics of resistance is crucial for optimizing patient care and developing effective therapeutic strategies. Further research is needed to monitor and control AMR in PIs in Mali.

Hematological profiles of patients with tuberculosis and nontuberculous mycobacteria infections in Bamako, Mali.

Background: Pulmonary tuberculosis (TB) remains one of the main causes of morbidity and mortality in Mali. Nontuberculous mycobacteria (NTM) infections are very common but are often cofounded with TB because of the similarity of symptoms, which makes the diagnosis difficult. Hematological abnormalities associated with TB have been described, but not with NTM. Therefore, the goal of this study was to compare the hematological parameters of patients infected with TB and NTM infections. Methods: A cross-sectional study enrolling TB and NTM participants was conducted in 2018-2020. Five milliliters of venous blood and sputum samples were collected from each participant to determine the hematological parameters using the RUBY CELL-DYN Ruby Version 2.2 ML. A BACTEC MGIT 960 and multiplex reverse transcription-polymerase chain reaction were used to distinguish Mycobacterium tuberculosis from NTM, respectively. Results: Of the total 90 patients enrolled, there was a decrease in hemoglobin and hematocrit levels in both the groups (P = 0.05). In addition, we found that the percentages of basophil cells (P = 0.01) and mean values of platelets (P = 0.04) were significantly higher in TB patients than those of NTMs. Moreover, the mean of absolute values of eosinophil cells of TB patients was significantly lower than those of NTMs (P = 0.03). Conclusion: We found significant statistical differences in basophils, platelets, and eosinophils in differentiating TB and NTM in this pilot study. Future studies with patients at different clinical stages are needed to confirm the hematological profiles of TB and NTM patients.

Metabolic and Immune Consequences of Antibiotic Related Microbiome Alterations during first-line Tuberculosis Treatment in Bamako, Mali.

Background: Tuberculosis (TB) infection is known to lead to the unbalance of the gut microbiota and act synergistically on the decline of the host immune response, when untreated. Moreover, previous work has found a correlation between dysbiosis in the gut microbiota composition and the use of antibiotics. However, there is a need for an in-depth understanding of the metabolic and immune consequences of antibiotic-related microbiome alterations during first-line TB treatment. Methods: In a longitudinal cohort study, which included TB-infected cohorts and healthy individuals (control group), we studied the anti-TB-related changes in the gut microbiota composition and related functional consequences. Sputum, whole blood and stool samples were collected from participants at four time-points including before (Month-0), during (Month-2), at the end of drug treatment (Month-6) and 9 months after treatment (Month-15). Controls were sampled at inclusion and Month-6. We analyzed the microbiota composition and microbial functional pathways with shotgun metagenomics, analyzed the blood metabolomics using high-performance liquid chromatography (HPLC), and measured the levels of metabolites and cytokines with cytometric bead array. Results: We found that the gut microbiota of patients infected with TB was different from that of the healthy controls. The gut microbiota became similar to healthy controls after treatment but was still significantly different after 6 months treatment and at the follow up 9 months after treatment. Our data also showed disturbance in the plasma metabolites such as tryptophan and tricarboxylic acids components of patients during TB treatment. Levels of IL-4, IL-6, IL-10, and IFN-γ decreased during treatment and levels were maintained after treatment completion, while IL-17A known to have a strong link with the gut microbiota was highly expressed during treatment period and longer than the 9-month post treatment completion. We found that some fatty acids were negatively correlated with the abundance of taxa. For example, Roseburia, Megasphaera, and alpha proteobacterium HIMB5 species were negatively correlated (rho = -0.6) with the quinolinate production. Conclusion: Changes in the composition and function of gut microbiota was observed in TB patients before and after treatment compared to healthy controls. The differences persisted at nine months after treatment completion. Alterations in some bacterial taxa were correlated to the changes in metabolite levels in peripheral blood, thus the altered microbial community might lead to changes in immune status that influence the disease outcome and future resistance to infections.

Relationship between patient sex and anatomical sites of extrapulmonary tuberculosis in Mali.

Background: Contribution of host factors in mediating susceptibility to extrapulmonary tuberculosis is not well understood. Objective: To examine the influence of patient sex on anatomical localization of extrapulmonary tuberculosis. Methods: We conducted a retrospective cross-sectional study in Mali, West Africa. Hospital records of 1,304 suspected cases of extrapulmonary tuberculosis, available in TB Registry of a tertiary tuberculosis referral center from 2019 to 2021, were examined. Results: A total of 1,012 (77.6%) were confirmed to have extrapulmonary tuberculosis with a male to female ratio of 1.59:1. Four clinical forms of EPTB predominated, namely pleural (40.4%), osteoarticular (29.8%), lymph node (12.5%), and abdominal TB (10.3%). We found sex-based differences in anatomical localization of extrapulmonary tuberculosis, with males more likely than females to have pleural TB (OR: 1.51; 95% CI [1.16 to 1.98]). Conversely, being male was associated with 43% and 41% lower odds of having lymph node and abdominal TB, respectively (OR: 0.57 and 0.59). Conclusion: Anatomical sites of extrapulmonary tuberculosis differ by sex with pleural TB being associated with male sex while lymph node and abdominal TB are predominately associated with female sex. Future studies are warranted to understand the role of sex in mediating anatomical site preference of tuberculosis.

Resurgence of Malaria Transmission and Incidence after Withdrawal of Indoor Residual Spraying in the District of Koulikoro, Mali.

In Mali, malaria vector control relies mostly on long-lasting insecticidal nets and indoor residual spraying (IRS). From 2008 to 2016, an IRS program was implemented in the district of Koulikoro. After a significant reduction in malaria indicators, IRS was stopped in 2016. This study evaluated the effect of IRS withdrawal on entomological parameters of malaria transmission and incidence in children aged 6 months to 10 years in the district of Koulikoro. Entomological parameters of malaria transmission during the last year of IRS implementation in 2016 were compared with those obtained 2 years after IRS withdrawal in 2018 in two villages of Koulikoro. Mosquito vectors were collected by mouth aspiration and pyrethrum spray catches in the villages to monitor these transmission parameters. A sharp increase (10.8 times higher) in vector abundance after IRS withdrawal was observed. The infection rate of Anopheles gambiae sensu lato to Plasmodium falciparum increased from zero during IRS implementation to 14.8% after IRS withdrawal. The average entomological inoculation rate, which was undetectable before, was 1.22 infected bites per person per month 2 years after IRS was withdrawn, and the cumulative malaria incidence rate observed after IRS was 4.12 times (15.2% versus 3.7%) higher than that observed in 2016 in the villages before IRS withdrawal. This study showed a resurgence of malaria transmission and incidence in the Koulikoro health district after IRS was withdrawn. Thus, to manage the potential consequences of malaria transmission resurgence, alternative approaches are needed when stopping successful malaria control interventions.

Malignancy and viral infections in Sub-Saharan Africa: A review.

The burden of malignancy related to viral infection is increasing in Sub-Saharan Africa (SSA). In 2018, approximately 2 million new cancer cases worldwide were attributable to infection. Prevention or treatment of these infections could reduce cancer cases by 23% in less developed regions and about 7% in developed regions. Contemporaneous increases in longevity and changes in lifestyle have contributed to the cancer burden in SSA. African hospitals are reporting more cases of cancer related to infection (e.g., cervical cancer in women and stomach and liver cancer in men). SSA populations also have elevated underlying prevalence of viral infections compared to other regions. Of 10 infectious agents identified as carcinogenic by the International Agency for Research on Cancer, six are viruses: hepatitis B and C viruses (HBV and HCV, respectively), Epstein-Barr virus (EBV), high-risk types of human papillomavirus (HPV), Human T-cell lymphotropic virus type 1 (HTLV-1), and Kaposi's sarcoma herpesvirus (KSHV, also known as human herpesvirus type 8, HHV-8). Human immunodeficiency virus type 1 (HIV) also facilitates oncogenesis. EBV is associated with lymphomas and nasopharyngeal carcinoma; HBV and HCV are associated with hepatocellular carcinoma; KSHV causes Kaposi's sarcoma; HTLV-1 causes T-cell leukemia and lymphoma; HPV causes carcinoma of the oropharynx and anogenital squamous cell cancer. HIV-1, for which SSA has the greatest global burden, has been linked to increasing risk of malignancy through immunologic dysregulation and clonal hematopoiesis. Public health approaches to prevent infection, such as vaccination, safer injection techniques, screening of blood products, antimicrobial treatments and safer sexual practices could reduce the burden of cancer in Africa. In SSA, inequalities in access to cancer screening and treatment are exacerbated by the perception of cancer as taboo. National level cancer registries, new screening strategies for detection of viral infection and public health messaging should be prioritized in SSA's battle against malignancy. In this review, we discuss the impact of carcinogenic viruses in SSA with a focus on regional epidemiology.

Genomic variation during culture adaptation of genetically complex Plasmodium falciparum clinical isolates.

Experimental studies on the biology of malaria parasites have mostly been based on laboratory-adapted lines, but there is limited understanding of how these may differ from parasites in natural infections. Loss-of-function mutants have previously been shown to emerge during culture of some Plasmodium falciparum clinical isolates in analyses focusing on single-genotype infections. The present study included a broader array of isolates, mostly representing multiple-genotype infections, which are more typical in areas where malaria is highly endemic. Genome sequence data from multiple time points over several months of culture adaptation of 28 West African isolates were analysed, including previously available sequences along with new genome sequences from additional isolates and time points. Some genetically complex isolates eventually became fixed over time to single surviving genotypes in culture, whereas others retained diversity, although proportions of genotypes varied over time. Drug resistance allele frequencies did not show overall directional changes, suggesting that resistance-associated costs are not the main causes of fitness differences among parasites in culture. Loss-of-function mutants emerged during culture in several of the multiple-genotype isolates, affecting genes (including AP2-HS, EPAC and SRPK1) for which loss-of-function mutants were previously seen to emerge in single-genotype isolates. Parasite clones were derived by limiting dilution from six of the isolates, and sequencing identified de novo variants not detected in the bulk isolate sequences. Interestingly, several of these were nonsense mutants and frameshifts disrupting the coding sequence of EPAC, the gene with the largest number of independent nonsense mutants previously identified in laboratory-adapted lines. Analysis of genomic identity by descent to explore relatedness among clones revealed co-occurring non-identical sibling parasites, illustrative of the natural genetic structure within endemic populations.

Clinical evaluation of commercial SARS-CoV-2 serological assays in a malaria endemic setting.

The levels of immune response to SARS-CoV-2 infection or vaccination are poorly understood in African populations and is complicated by cross-reactivity to endemic pathogens as well as differences in host responsiveness. To begin to determine the best approach to minimize false positive antibody levels to SARS-CoV-2 in an African population, we evaluated three commercial assays, namely Bio-Rad Platelia SARS-CoV-2 Total Antibody (Platelia), Quanterix Simoa Semi-Quantitative SARS-CoV-2 IgG Antibody Test (anti-Spike), and the GenScript cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit (cPass) using samples collected in Mali in West Africa prior to the emergence of SARS-CoV-2. A total of one hundred samples were assayed. The samples were categorized in two groups based on the presence or absence of clinical malaria. Overall, thirteen out of one hundred (13/100) samples were false positives with the Bio-Rad Platelia assay and one of the same one hundred (1/100) was a false positive with the anti-Spike IgG Quanterix assay. None of the samples tested with the GenScript cPass assay were positive. False positives were more common in the clinical malaria group, 10/50 (20%) vs. the non-malaria group 3/50 (6%); p = 0.0374 using the Bio-Rad Platelia assay. Association between false positive results and parasitemia by Bio-Rad remained evident, after adjusting for age and sex in multivariate analyses. In summary, the impact of clinical malaria on assay performance appears to depend on the assay and/or antigen being used. A careful evaluation of any given assay in the local context is a prerequisite for reliable serological assessment of anti-SARS-CoV-2 humoral immunity.

Type 2 diabetes prevalence, awareness, and risk factors in rural Mali: a cross-sectional study.

Diabetes is currently a crisis in sub-Saharan West Africa (SSWA) with dramatic implications for public health and national budgets prioritizing infectious diseases. There is limited recent literature about the prevalence, awareness, and risk factors for type 2 diabetes (T2D) in rural parts of SSWA. This study characterized T2D prevalence and risk factors for the rural Malian community of Nièna, which is situated in Mali's second-largest province of Sikasso. Between December 2020 and July 2021, a cross-sectional study of 412 participants was conducted in the Nièna community using clinical questionnaires and rapid diagnostic tests. Among 412 participants, there were 143 (34.7%) and 269 (65.3%) males and females, respectively. The overall prevalence of T2D in Nièna was 7.5% (31/412), and prevalence rates were 8.6% (23/269) and 5.6% (8/143) for females and males, respectively. Age, family history of diabetes, hypertension, waist circumference, and fetal macrosomia were significantly associated with T2D (p = 0.007, p < 0.001, p = 0.003, p = 0.013, and p < 0.001, respectively). Notably, 61.3% (19/31) of T2D subjects were unaware of their diabetic status before the study. Field surveys have considerable utility in driving T2D awareness in rural African settings.

Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples.

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network.  It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented.  For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations.  We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent.  We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines.  Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website.

Hepatitis B Virus in West African Children: Systematic Review and Meta-Analysis of HIV and Other Factors Associated with Hepatitis B Infection.

While Hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are endemic in West Africa, the prevalence of HBV/HIV coinfection and their associated risk factors in children remains unclear. In this review, we sought to assess HBsAg seroprevalence among 0- to 16-year-olds with and without HIV in West African countries and the risk factors associated with HBV infection in this population. Research articles between 2000 and 2021 that reported the prevalence of HBV and associated risk factors in children in West Africa were retrieved from the literature using the Africa Journals Online (AJOL), PubMed, Google Scholar, and Web of Science databases as search tools. StatsDirect, a statistical software, was used to perform a meta-analysis of the retained studies. HBV prevalence and heterogeneity were then assessed with a 95% confidence interval (CI). Publication bias was evaluated using funnel plot asymmetry and Egger's test. Twenty-seven articles conducted across seven West African countries were included in this review. HBV prevalence among persons aged 0 to 16 years was 5%, based on the random analysis, given the great heterogeneity of the studies. By country, the highest prevalence was observed in Benin (10%), followed by Nigeria (7%), and Ivory Coast (5%), with Togo (1%) having the lowest. HBV prevalence in an HIV-infected population of children was (9%). Vaccinated children had lower HBV prevalence (2%) than unvaccinated children (6%). HBV prevalence with a defined risk factor such as HIV co-infection, maternal HBsAg positivity, undergoing surgery, scarification, or being unvaccinated ranged from 3-9%. The study highlights the need to reinforce vaccination of newborns, screening for HBV, and HBV prophylaxis among pregnant women in Africa, particularly in West Africa, to achieve the WHO goal of HBV elimination, particularly in children.

IFNγ, TNFα polymorphisms and IFNγ serum levels are associated with the clearance of drug-resistant P. falciparum in Malian children.

Host immunity has been suggested to clear drug-resistant parasites in malaria-endemic settings. However, the immunogenetic mechanisms involved in parasite clearance are poorly understood. Characterizing the host's immunity and genes involved in controlling the parasitic infection can inform the development of blood-stage malaria vaccines. This study investigates host regulatory cytokines and immunogenomic factors associated with the clearance of Plasmodium falciparum carrying a chloroquine resistance genotype. Biological samples from participants of previous drug efficacy trials conducted in two Malian localities were retrieved. The P. falciparum chloroquine resistance transporter (Pfcrt) gene was genotyped using parasite DNA. Children carrying parasites with the mutant allele (Pfcrt-76T) were classified based on their ability to clear their parasites. The levels of the different cytokines were measured in serum. The polymorphisms of specific human genes involved in malaria susceptibility were genotyped using human DNA. The prevalence of the Pfcrt-76T was significantly higher in Kolle than in Bandiagara (81.6 % vs 38.6 %, p < 10-6). The prevalence of children who cleared their mutant parasites was significantly higher in Bandiagara than in Kolle (82.2 % vs 67.4 %, p < 0.05). The genotyping of host genes revealed that IFN-γ -874 T and TNF-α -308A alleles were positively associated with parasite clearance. Cytokine profiling revealed that IFN-γ level was positively associated with parasite clearance (p = 0.04). This study highlights the role of host's immunity and immunogenetic factors to clear resistant parasites, suggesting further characterization of these polymorphisms may help to develop novel approaches to antiparasitic treatment strategies.

Effect of a fifth round of seasonal malaria chemoprevention in children aged 5-14 years in Dangassa, an area of long transmission in Mali.

Despite a significant reduction in the burden of malaria in children under five years-old, the efficient implementation of seasonal malaria chemoprevention (SMC) at large scale remains a major concern in areas with long malaria transmission. Low coverage rate in the unattainable areas during the rainy season, a shift in the risk of malaria to older children and the rebound in malaria incidence after stopping drug administration are mainly reported in these areas. These gaps represent a major challenge in the efficient implementation of SMC measures. An open randomized study was conducted to assess the effect of a fifth additional round to current regime of SMC in older children living in Dangassa, a rural malaria endemic area. Poisson regression Model was used to estimate the reduction in malaria incidence in the intervention group compared to the control group including age groups (5-9 and 10-14 years) and the use of long-lasting insecticidal nets (LLINs; Yes or No) with a threshold at 5%. Overall, a downward trend in participation rate was observed from August (94.3%) to November (87.2%). In November (round 4), the risk of malaria incidence was similar in both groups (IRR = 0.66, 95%CI [0.35-1.22]). In December (round 5), a decrease of 51% in malaria incidence was observed in intervention group compared to control group adjusted for age groups and the use of LLINs (IRR = 0.49, 95%CI [0.26-0.94]), of which 17% of reduction is attributable to the 5th round in the intervention group. An additional fifth round of SMC resulted in a significant reduction of malaria incidence in the intervention group. The number of SMC rounds could be adapted to the local condition of malaria transmission.

Dynamics of SARS-CoV-2 variants characterized during different COVID-19 waves in Mali.

Background: The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants may have contributed to prolonging the pandemic, and increasing morbidity and mortality related to coronavirus disease 2019 (COVID-19). This article describes the dynamics of circulating SARS-CoV-2 variants identified during the different COVID-19 waves in Mali between April and October 2021. Methods: The respiratory SARS-CoV-2 complete spike (S) gene from positive samples was sequenced. Generated sequences were aligned by Variant Reporter v3.0 using the Wuhan-1 strain as the reference. Mutations were noted using the GISAID and Nextclade platforms. Results: Of 16,797 nasopharyngeal swab samples tested, 6.0% (1008/16,797) tested positive for SARS-CoV-2 on quantitative reverse transcription polymerase chain reaction. Of these, 16.07% (162/1008) had a cycle threshold value ≤28 and were amplified and sequenced. The complete S gene sequence was recovered from 80 of 162 (49.8%) samples. Seven distinct variants were identified: Delta (62.5%), Alpha (1.2%), Beta (1.2%), Eta (30.0%), 20B (2.5%), 19B (1.2%) and 20A (1.2%). Conclusions and perspectives: Several SARS-CoV-2 variants were present during the COVID-19 waves in Mali between April and October 2021. The continued emergence of new variants highlights the need to strengthen local real-time sequencing capacity and genomic surveillance for better and coordinated national responses to SARS-CoV-2.

The West Africa ICEMR Partnerships for Guiding Policy to Improve the Malaria Prevention and Control.

The Mali National Malaria Control Program (NMCP) recently established a phased set of goals for eliminating malaria in Mali by 2030. Over the past decade, the scale-up of NMCP-led malaria control interventions has led to considerable progress, as evidenced by multiple malariometric indicators. The West Africa International Center of Excellence in Malaria Research (WA-ICEMR) is a multidisciplinary research program that works closely with the NMCP and its partners to address critical research needs for malaria control. This coordinated effort includes assessing the effectiveness of control interventions based on key malaria research topics, including immune status, parasite genetic diversity, insecticide and drug resistance, diagnostic accuracy, malaria vector populations and biting behaviors, and vectorial capacity. Several signature accomplishments of the WA-ICEMR include identifying changing malaria age demographic profiles, testing innovative approaches to improve control strategies, and providing regular reporting on drug and insecticide resistance status. The NMCP and WA-ICEMR partnership between the WA-ICEMR and the NMCP offers a comprehensive research platform that informs the design and implementation of malaria prevention and control research programs. These efforts build local expertise and capacity for the next generation of malaria researchers and guide local policy, which is crucial in sustaining efforts toward eliminating malaria in West Africa.