Immune gene expression changes more during a malaria transmission season than between consecutive seasons.

Plasmodium parasites, the causative organism of malaria, caused over 600,000 deaths in 2022. In Mali, Plasmodium falciparum causes the majority of malaria cases and deaths and is transmitted seasonally. Anti-malarial immunity develops slowly over repeated exposures to P. falciparum and some aspects of this immunity (e.g., antibody titers) wane during the non-transmission, dry season. Here, we sequenced RNA from 33 pediatric blood samples collected during P. falciparum infections at the beginning or end of a transmission season, and characterized the host and parasite gene expression profiles for paired, consecutive infections. We found that human gene expression changes more over the course of one transmission season than between seasons, with signatures of partial development of an adaptive immune response during one transmission season and stability in gene expression during the dry season. Additionally, we found that P. falciparum gene expression did not vary with timing during the season and remained stable both across and between seasons, despite varying human immune pressures. Our results provide insights into the dynamics of anti-malarial immune response development over short time frames that could be exploited by future vaccine and prevention efforts. IMPORTANCE: Our work seeks to understand how the immune response to Plasmodium falciparum malaria changes between infections that occur during low and high malaria transmission seasons, and highlights that immune gene expression changes more during the high transmission season. This provides important insight into the dynamics of the anti-malarial immune response that are important to characterize over these short time frames to better understand how to exploit this immune response with future vaccine efforts.

Children with hemoglobin C or S trait have low serologic responses to a subset of malaria variant surface antigens.

Children with hemoglobin AC or AS have decreased susceptibility to clinical malaria. Parasite variant surface antigen (VSA) presentation on the surface of infected erythrocytes is altered in erythrocytes with hemoglobin C (Hb AC) or sickle trait (Hb AS) mutations in vitro. The protective role of incomplete or altered VSA presentation against clinical malaria in individuals with Hb AC or AS is unclear. Using a high-throughput protein microarray, we sought to use serological responses to VSAs as a measure of host exposure to VSAs among Malian children with Hb AC, Hb AS, or wildtype hemoglobin (Hb AA). In uncomplicated malaria, when compared to Hb AA children, Hb AC children had significantly lower serological responses to extracellular Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) domains but did not differ in responses to intracellular PfEMP1 domains and other VSAs, including members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family. Healthy children with Hb AC and Hb AS genotypes recognized fewer extracellular PfEMP1s compared to children with Hb AA, especially CD36-binding PfEMP1s. These reduced serologic responses may reflect reduced VSA presentation or lower parasite exposure in children with Hb AC or AS and provide insights into mechanisms of protection.

Gene expression analyses reveal differences in children's response to malaria according to their age.

In Bandiagara, Mali, children experience on average two clinical malaria episodes per year. However, even in the same transmission area, the number of uncomplicated symptomatic infections, and their parasitemia, can vary dramatically among children. We simultaneously characterize host and parasite gene expression profiles from 136 Malian children with symptomatic falciparum malaria and examine differences in the relative proportion of immune cells and parasite stages, as well as in gene expression, associated with infection and or patient characteristics. Parasitemia explains much of the variation in host and parasite gene expression, and infections with higher parasitemia display proportionally more neutrophils and fewer T cells, suggesting parasitemia-dependent neutrophil recruitment and/or T cell extravasation to secondary lymphoid organs. The child's age also strongly correlates with variations in gene expression: Plasmodium falciparum genes associated with age suggest that older children carry more male gametocytes, while variations in host gene expression indicate a stronger innate response in younger children and stronger adaptive response in older children. These analyses highlight the variability in host responses and parasite regulation during P. falciparum symptomatic infections and emphasize the importance of considering the children's age when studying and treating malaria infections.

Characteristics of Hospitalized COVID-19 Patients at Admission and Factors Associated with Clinical Severity in Low- and Middle-Income Countries: An Observational Study.

Despite the numerous articles published on the clinical characteristics and outcomes of COVID-19 with regard to high-income countries, little is known about patients in low- and middle-income countries (LMIC) in this context. The objective of this observational, prospective, hospital-based multicentric study was to describe clinical features and outcomes of laboratory-confirmed COVID-19 patients hospitalized in each of the participating centers in Bangladesh, Guinea, Ivory Coast, Lebanon, Madagascar, and Mali during the first year of the pandemic (March 5, 2020 to May 4, 2021). The study outcome was the clinical severity of COVID-19, defined as hospitalization in intensive care unit or death. Multivariate logistic regression models were performed to identify independent variables associated with disease severity. Overall, 1,096 patients were included. The median age was 49.0 years, ranging from 38.0 in Mali to 63.0 years in Guinea. The overall clinical severity of COVID-19 was 12.3%, ranging from 6.4% in Mali to 18.8% in Guinea. In both groups of patients <60 and ≥60 years old, cardiovascular diseases (adjusted odds ratio [aOR]: 1.99; 95% CI: 1.13-3.50, P = 0.02; aOR: 2.47; 95% CI: 1.33-4.57, P = 0.004) were independently associated with clinical severity, whereas in patients <60 years, diabetes (aOR: 2.13; 95% CI: 1.11-4.10, P = 0.02) was also associated with clinical severity. Our findings suggest that COVID-19-related severity and death in LMICs are mainly driven by older age. However, the presence of chronic diseases can also increase the risk of severity especially in younger patients.

Carence en vitamine D et risque de cancer du sein avancé au Mali / Vitamin D deficiency in advanced breast cancer risk in Mali

Objectif : Le but de cette étude était de déterminer une association entre la carence en vitamine D et le cancer du sein avancé chez une population de femmes maliennes. Méthodes : Il s'agit d'une étude prospective transversale, menée pendant 4 mois, d'Août à novembre 2021. Les dosages ont été réalisés au laboratoire Rodolphe Mérieux. Résultats : Nous avons inclus 77 femmes diagnostiquées pour un cancer du sein avancé. L'âge moyen de la population étudiée était de 48,51 ± 13,02 ans. Les concentrations plasmatiques moyennes de 25(OH)D étaient respectivement de 20,65 ± 6,76 et 18,89 ± 6,12 ng/ml (p=0,274) dans les groupes III et IV. Le stade III était majoritaire avec 67,5% et il n'y avait pas de différences significatives avec le stade IV pour les marqueurs biologiques phospho-calciques. Nos résultats ont montré une carence en vitamine D plus importante au stade III qu'au stade IV, avec p=0.782. Le modèle de régression logistique a montré une diminution significative du risque relatif de cancer du sein avancé selon les quartiles de vitamine D (p=0.039). Il n'y avait pas d'association avec la calcémie, la phosphatémie, la créatinine plasmatique et le débit de filtration glomérulaire (DFG) (p>0,05). Conclusions : Nos résultats suggèrent une association entre la vitamine D et le risque de cancer du sein avancé aux stades III et IV. Cependant, d'autres études sont nécessaires pour confirmer le rôle de la vitamine D dans l'évolution du cancer du sein féminin aux stades avancés

Aims: The aim of this study was to determine the association between vitamin D deficiency and advanced BC in a Malian women population. Methods: This is a prospective cross-sectional study, conducted during 4 months, from August 2021 to November 2021. The assays were performed on immunodiagnostic and biochemistry devices in Rodolphe Merieux Laboratory. Results: We included 77 women diagnosed with advanced breast cancer. The mean age of the study population was 48.51 ± 13.02 years. The mean plasma concentrations of 25(OH)D were 20.65 ± 6.76 ng/ml and 18.89 ± 6.12 ng/ml (p=0.274) in groups III and IV, respectively. Stage III was predominant, comprising 67.5% of the cases, and there were no significant differences between stages III and IV regarding phospho-calcium biological markers. Our results showed a greater deficiency in vitamin D at stage III compared to stage IV, with p=0.782. The logistic regression model demonstrated a significant decrease in the relative risk of advanced breast cancer across the quartiles of vitamin D (p=0.039). There was no association with serum calcium, phosphate, plasma creatinine, and glomerular filtration rate (GFR) (p>0.05). Conclusions: Our findings show an decrease of the risk of breast cancer about vitamin D levels in our population. These results suggest an association between vitamin D and the risk of advanced breast cancer. Further studies are needed to determine the mechanism of vitamin D deficiency in advanced breast cancer.

Plasma 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels in Breast Cancer Risk in Mali: A Case-Control Study.

(1) Background: Breast cancer is the most prevalent cancer found in women in Mali. The aim of the current study was to determine the association between metabolites circulating in the blood, 25(OH)D and 1,25(OH)2D, and vitamin D levels with the risk of breast cancer in Malian women. (2) Methods: We conducted a prospective case-control study from August 2021 to March 2022. Control subjects were matched to cases according to age (within 5 years). The patients' clinical stage was determined by the oncologist according to the tumour-nodes-metastasis (TNM) classification system. (3) Results: We observed no differences in the mean 25(OH)D (p = 0.221) and 1,25(OH)2D (p = 0.285) between cases and controls. However, our findings indicate a more pronounced inverse association in the first level of plasma 25(OH)D, while the risk function decreases at higher levels. This observation takes strength with 1,25(OH)2D by a significant association between the first quartile and breast cancer as a risk factor (p = 0.03; OR = 71.84; CI: 1.36-3785.34). (4) Conclusions: These outcomes showed a possible association between 25(OH)D and 1,25(OH)2D in decreasing the risk of breast cancer.

Gene expression analyses reveal differences in children's response to malaria according to their age.

In Bandiagara, Mali, children experience on average two clinical malaria episodes per season. However, even in the same transmission area, the number of uncomplicated symptomatic infections, and their parasitemia, vary dramatically among children. To examine the factors contributing to these variations, we simultaneously characterized the host and parasite gene expression profiles from 136 children with symptomatic falciparum malaria and analyzed the expression of 9,205 human and 2,484 Plasmodium genes. We used gene expression deconvolution to estimate the relative proportion of immune cells and parasite stages in each sample and to adjust the differential gene expression analyses. Parasitemia explained much of the variation in both host and parasite gene expression and revealed that infections with higher parasitemia had more neutrophils and fewer T cells, suggesting parasitemia-dependent neutrophil recruitment and/or T cell extravasation to secondary lymphoid organs. The child's age was also strongly correlated with gene expression variations. Plasmodium falciparum genes associated with age suggested that older children carried more male gametocytes, while host genes associated with age indicated a stronger innate response (through TLR and NLR signaling) in younger children and stronger adaptive immunity (through TCR and BCR signaling) in older children. These analyses highlight the variability in host responses and parasite regulation during P. falciparum symptomatic infections and emphasize the importance of considering the children's age when studying and treating malaria infections.

Gene expression analyses reveal differences in children's response to malaria according to their age.

In Bandiagara, Mali, children experience on average two clinical malaria episodes per season. However, even in the same transmission area, the number of uncomplicated symptomatic infections, and their parasitemia, vary dramatically among children. To examine the factors contributing to these variations, we simultaneously characterized the host and parasite gene expression profiles from 136 children with symptomatic falciparum malaria and analyzed the expression of 9,205 human and 2,484 Plasmodium genes. We used gene expression deconvolution to estimate the relative proportion of immune cells and parasite stages in each sample and to adjust the differential gene expression analyses. Parasitemia explained much of the variation in both host and parasite gene expression and revealed that infections with higher parasitemia had more neutrophils and fewer T cells, suggesting parasitemia-dependent neutrophil recruitment and/or T cell extravasation to secondary lymphoid organs. The child's age was also strongly correlated with gene expression variations. Plasmodium falciparum genes associated with age suggested that older children carried more male gametocytes, while host genes associated with age indicated a stronger innate response (through TLR and NLR signaling) in younger children and stronger adaptive immunity (through TCR and BCR signaling) in older children. These analyses highlight the variability in host responses and parasite regulation during P. falciparum symptomatic infections and emphasize the importance of considering the children's age when studying and treating malaria infections.

Natural immunity to malaria preferentially targets the endothelial protein C receptor-binding regions of PfEMP1s.

Antibody responses to variant surface antigens (VSAs) produced by the malaria parasite Plasmodium falciparum may contribute to age-related natural immunity to severe malaria. One VSA family, P. falciparum erythrocyte membrane protein-1 (PfEMP1), includes a subset of proteins that binds endothelial protein C receptor (EPCR) in human hosts and potentially disrupts the regulation of inflammatory responses, which may lead to the development of severe malaria. We probed peptide microarrays containing segments spanning five PfEMP1 EPCR-binding domain variants with sera from 10 Malian adults and 10 children to determine the differences between adult and pediatric immune responses. We defined serorecognized peptides and amino acid residues as those that elicited a significantly higher antibody response than malaria-naïve controls. We aimed to identify regions consistently serorecognized among adults but not among children across PfEMP1 variants, potentially indicating regions that drive the development of immunity to severe malaria. Adult sera consistently demonstrated broader and more intense serologic responses to constitutive PfEMP1 peptides than pediatric sera, including peptides in EPCR-binding domains. Both adults and children serorecognized a significantly higher proportion of EPCR-binding peptides than peptides that do not directly participate in receptor binding, indicating a preferential development of serologic responses at functional residues. Over the course of a single malaria transmission season, pediatric serological responses increased between the start and the peak of the season, but waned as the transmission season ended. IMPORTANCE Severe malaria and death related to malaria disproportionately affect sub-Saharan children under 5 years of age, commonly manifesting as cerebral malaria and/or severe malarial anemia. In contrast, adults in malaria-endemic regions tend to experience asymptomatic or mild disease. Our findings indicate that natural immunity to malaria targets specific regions within the EPCR-binding domain, particularly peptides containing EPCR-binding residues. Epitopes containing these residues may be promising targets for vaccines or therapeutics directed against severe malaria. Our approach provides insight into the development of natural immunity to a binding target linked to severe malaria by characterizing an "adult-like" response as recognizing a proportion of epitopes within the PfEMP1 protein, particularly regions that mediate EPCR binding. This "adult-like" response likely requires multiple years of malaria exposure, as increases in pediatric serologic response over a single malaria transmission season do not appear significant.

Immunogenomic profile at baseline predicts host susceptibility to clinical malaria.

Introduction: Host gene and protein expression impact susceptibility to clinical malaria, but the balance of immune cell populations, cytokines and genes that contributes to protection, remains incompletely understood. Little is known about the determinants of host susceptibility to clinical malaria at a time when acquired immunity is developing. Methods: We analyzed peripheral blood mononuclear cells (PBMCs) collected from children who differed in susceptibility to clinical malaria, all from a small town in Mali. PBMCs were collected from children aged 4-6 years at the start, peak and end of the malaria season. We characterized the immune cell composition and cytokine secretion for a subset of 20 children per timepoint (10 children with no symptomatic malaria age-matched to 10 children with >2 symptomatic malarial illnesses), and gene expression patterns for six children (three per cohort) per timepoint. Results: We observed differences between the two groups of children in the expression of genes related to cell death and inflammation; in particular, inflammatory genes such as CXCL10 and STAT1 and apoptotic genes such as XAF1 were upregulated in susceptible children before the transmission season began. We also noted higher frequency of HLA-DR+ CD4 T cells in protected children during the peak of the malaria season and comparable levels cytokine secretion after stimulation with malaria schizonts across all three time points. Conclusion: This study highlights the importance of baseline immune signatures in determining disease outcome. Our data suggests that differences in apoptotic and inflammatory gene expression patterns can serve as predictive markers of susceptibility to clinical malaria.

Characterization of a novel Plasmodium falciparum merozoite surface antigen and potential vaccine target.

Introduction: Detailed analyses of genetic diversity, antigenic variability, protein localization and immunological responses are vital for the prioritization of novel malaria vaccine candidates. Comprehensive approaches to determine the most appropriate antigen variants needed to provide broad protection are challenging and consequently rarely undertaken. Methods: Here, we characterized PF3D7_1136200, which we named Asparagine-Rich Merozoite Antigen (ARMA) based on the analysis of its sequence, localization and immunogenicity. We analyzed IgG and IgM responses against the common variants of ARMA in independent prospective cohort studies in Burkina Faso (N = 228), Kenya (N = 252) and Mali (N = 195) using a custom microarray, Div-KILCHIP. Results: We found a marked population structure between parasites from Africa and Asia. African isolates shared 34 common haplotypes, including a dominant pair although the overall selection pressure was directional (Tajima's D = -2.57; Fu and Li's F = -9.69; P < 0.02). ARMA was localized to the merozoite surface, IgG antibodies induced Fc-mediated degranulation of natural killer cells and strongly inhibited parasite growth in vitro. We found profound serological diversity, but IgG and IgM responses were highly correlated and a hierarchical clustering analysis identified only three major serogroups. Protective IgG and IgM antibodies appeared to target both cross-reactive and distinct epitopes across variants. However, combinations of IgG and IgM antibodies against selected variants were associated with complete protection against clinical episodes of malaria. Discussion: Our systematic strategy exploits genomic data to deduce the handful of antigen variants with the strongest potential to induce broad protection and may be broadly applicable to other complex pathogens for which effective vaccines remain elusive.

SARS-CoV-2 seroprevalence and living conditions in Bamako (Mali): a cross-sectional multistage household survey after the first epidemic wave, 2020.

OBJECTIVES: In low-income settings with limited access to diagnosis, COVID-19 information is scarce. In September 2020, after the first COVID-19 wave, Mali reported 3086 confirmed cases and 130 deaths. Most reports originated from Bamako, with 1532 cases and 81 deaths (2.42 million inhabitants). This observed prevalence of 0.06% appeared very low. Our objective was to estimate SARS-CoV-2 infection among inhabitants of Bamako, after the first epidemic wave. We assessed demographic, social and living conditions, health behaviours and knowledges associated with SARS-CoV-2 seropositivity. SETTINGS: We conducted a cross-sectional multistage household survey during September 2020, in three neighbourhoods of the commune VI (Bamako), where 30% of the cases were reported. PARTICIPANTS: We recruited 1526 inhabitants in 3 areas, that is, 306 households, and 1327 serological results (≥1 years), 220 household questionnaires and collected answers for 962 participants (≥12 years). PRIMARY AND SECONDARY OUTCOME MEASURES: We measured serological status, detecting SARS-CoV-2 spike protein antibodies in blood sampled. We documented housing conditions and individual health behaviours through questionnaires among participants. We estimated the number of SARS-CoV-2 infections and deaths in the population of Bamako using the age and sex distributions. RESULTS: The prevalence of SARS-CoV-2 seropositivity was 16.4% (95% CI 15.1% to 19.1%) after adjusting on the population structure. This suggested that ~400 000 cases and ~2000 deaths could have occurred of which only 0.4% of cases and 5% of deaths were officially reported. Questionnaires analyses suggested strong agreement with washing hands but lower acceptability of movement restrictions (lockdown/curfew), and mask wearing. CONCLUSIONS: The first wave of SARS-CoV-2 spread broadly in Bamako. Expected fatalities remained limited largely due to the population age structure and the low prevalence of comorbidities. Improving diagnostic capacities to encourage testing and preventive behaviours, and avoiding the spread of false information remain key pillars, regardless of the developed or developing setting. ETHICS: This study was registered in the registry of the ethics committee of the Faculty of Medicine and Odonto-Stomatology and the Faculty of Pharmacy, Bamako, Mali, under the number: 2020/162/CA/FMOS/FAPH.

First Molecular Characterization of Chronic Hepatitis B Carriers in Timbuktu, Mali.

In Mali, hepatocellular carcinoma (HCC) is the third and sixth most common cancer in men and women, respectively. Mali comprises several distinct climato-ecological zones. Most studies to date have been conducted in the sub-Sahelian zone of southern Mali, including the capital city Bamako. In this part of the country, the main risk factors for HCC are chronic hepatitis B virus (HBV) carriage and dietary exposure to aflatoxins, a well-known hepatocarcinogen. Data are scarce for other ecological zones, but our preliminary data from 721 blood donors in the area of Timbuktu, presented in this study, suggest that chronic HBV carriage is also endemic in the northern Saharan zone of Mali. For further study, 29 healthy HBV chronic carrier volunteers were recruited from the blood transfusion center in Timbuktu. Successful viral genotyping in 20 volunteers revealed HBV genotype E in 13 cases and D in 7 cases, suggesting that this geographical and anthropological transition zone may also represent a transition zone between HBV genotypes that dominate sub-Saharan and northern Africa, respectively. Sequencing of circulating cell-free plasma DNA (cfDNA) from donors did not reveal the presence of the TP53 R249S mutation in these donors, a marker of dietary exposure to aflatoxins in sub-Saharan Africa. These results suggest that the geo-epidemiological distribution of the risk factors for HCC is not uniform across Mali, but is dependent upon climatic, socioeconomic and anthropological factors that might have an impact on patterns of chronic liver disease and cancer.

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.

Malian children infected with Plasmodium ovale and Plasmodium falciparum display very similar gene expression profiles.

Plasmodium parasites caused 241 million cases of malaria and over 600,000 deaths in 2020. Both P. falciparum and P. ovale are endemic to Mali and cause clinical malaria, with P. falciparum infections typically being more severe. Here, we sequenced RNA from nine pediatric blood samples collected during infections with either P. falciparum or P. ovale, and characterized the host and parasite gene expression profiles. We found that human gene expression varies more between individuals than according to the parasite species causing the infection, while parasite gene expression profiles cluster by species. Additionally, we characterized DNA polymorphisms of the parasites directly from the RNA-seq reads and found comparable levels of genetic diversity in both species, despite dramatic differences in prevalence. Our results provide unique insights into host-pathogen interactions during malaria infections and their variations according to the infecting Plasmodium species, which will be critical to develop better elimination strategies against all human Plasmodium parasites.

Risque de transmission de certains arbovirus à travers le don de sang à Bamako / Risk of transmission of certain arbovirus through blood donation in the city of Bamako

Introduction. Au Mali, le dépistage de certains virus tels que la dengue, Zika et la fièvre de la vallée du Rift n'est pas systématique au centre national de transfusion sanguine (CNTS). Le risque peut être considérable en raison de leurs courtes périodes de virémie asymptomatique dans la population dont l'incidence est variable et parfois extrêmement élevée. Cette étude avait pour objectif d'explorer la possibilité de transmission de certains arbovirus à travers le don de sang au CNTS de Bamako. Méthodes. Il s'agissait d'une étude transversale, de juillet 2019 à juin 2020 à Bamako. Au total deux cents (200) donneurs de sang du CNTS ont été inclus. Les examens ont été réalisés au Centre d'Infectiologie Charles Mérieux (CICM) de Bamako avec le dépistage du génome des virus responsables de la Dengue, de la fièvre de la Vallée du Rift, et du Zika à l'aide de la technique de la RT-PCR en temps réel. Le Test de Dépistage Rapide (TDR) a été utilisé pour la détection des anticorps IgG et IgM spécifiques de la Dengue. Résultats. Le sexe masculin représente 84% (168/200). Le TDR a détecté 4,5% (9/200) de Dengue IgG positifs et aucun cas de Dengue IgM positif. La technique de RT-PCR n'a détecté aucun des trois virus. Conclusion. Cette étude prouve que le risque de transmission de certains arbovirus à travers le don de sang existe, mais il semble être minime au CNTS de Bamako

Background. In Mali, screening for certain viruses such as dengue, Zika, and Rift Valley fever is not systematic at the national blood transfusion center (CNTS). The risk can be considerable due to their short periods of asymptomatic viremia in the population with variable and sometimes extremely high incidence. The objective of this study was to explore the possibility of transmission of certain arboviruses through blood donation at the CNTS of Bamako. Methods. This was a cross-sectional study, from July 2019 to June 2020 in Bamako. A total of two hundred (200) blood donors from the CNTS were included. The examinations were performed at the Centre d'Infectiologie Charles Mérieux (CICM) in Bamako with the screening of the genome of viruses responsible for Dengue, Rift Valley fever, and Zika using the real-time RT-PCR technique. The Rapid Screening Test (RST) was used for the detection of Dengue-specific IgG and IgM antibodies. Results. Male sex represented 84% (168/200). The RDT detected 4.5% (9/200) of IgG positive Dengue and no IgM positive Dengue cases. The RT-PCR technique did not detect any of the three viruses. Conclusion. This study proves that the risk of transmission of certain arboviruses through blood donation exists, but it seems to be minimal at the CNTS of Bamako.

PfSPZ-CVac malaria vaccine demonstrates safety among malaria-experienced adults: A randomized, controlled phase 1 trial.

Background: Plasmodium falciparum (Pf) Sporozoite (SPZ) Chemoprophylaxis Vaccine (PfSPZ-CVac) involves concurrently administering infectious PfSPZ and malaria drug, often chloroquine (CQ), to kill liver-emerging parasites. PfSPZ-CVac (CQ) protected 100% of malaria-naïve participants against controlled human malaria infection. We investigated the hypothesis that PfSPZ-CVac (CQ) is safe and efficacious against seasonal, endemic Pf in malaria-exposed adults. Methods: Healthy 18-45 year olds were enrolled in a double-blind, placebo-controlled trial in Bougoula-Hameau, Mali, randomized 1:1 to 2.048 × 105 PfSPZ (PfSPZ Challenge) or normal saline administered by direct venous inoculation at 0, 4, 8 weeks. Syringes were prepared by pharmacy staff using online computer-based enrolment that randomized allocations. Clinical team and participant masking was assured by identical appearance of vaccine and placebo. Participants received chloroquine 600mg before first vaccination, 10 weekly 300mg doses during vaccination, then seven daily doses of artesunate 200mg before 24-week surveillance during the rainy season. Safety outcomes were solicited adverse events (AEs) and related unsolicited AEs within 12 days of injections, and all serious AEs. Pf infection was detected by thick blood smears performed every four weeks and during febrile illness over 48 weeks. Primary vaccine efficacy (VE) endpoint was time to infection at 24 weeks. NCT02996695. Findings: 62 participants were enrolled in April/May 2017. Proportions of participants experiencing at least one solicited systemic AE were similar between treatment arms: 6/31 (19.4%, 95%CI 9.2-36.3) of PfSPZ-CVac recipients versus 7/31 (22.6%, 95%CI 29.2-62.2) of controls (p value = 1.000). Two/31 (6%) in each group reported related, unsolicited AEs. One unrelated death occurred. Of 59 receiving 3 immunizations per protocol, fewer vaccinees (16/29, 55.2%) became infected than controls (22/30, 73.3%). VE was 33.6% by hazard ratio (p = 0.21, 95%CI -27·9, 65·5) and 24.8% by risk ratio (p = 0.10, 95%CI -4·8, 54·3). Antibody responses to PfCSP were poor; 28% of vaccinees sero-converted. Interpretation: PfSPZ-CVac (CQ) was well-tolerated. The tested dosing regimen failed to significantly protect against Pf infection in this very high transmission setting. Funding: U.S. National Institutes of Health, Sanaria. Registration number: ClinicalTrials.gov identifier (NCT number): NCT02996695.

Monitoring of glycemic balance by glycated hemoglobin assay on D-10® (Biorad) and Minicap Flex Piercing® (Sebia) biochemical systems at the Rodolph-Mérieux Laboratory in Bamako / Suivi de l'équilibre glycémique par le dosage de l'hémoglobine glyquée sur les automates de biochimie D-10® (Biorad) et Minicap Flex Piercing® (Sebia) au Laboratoire RodolpheMérieux de Bamako

This study aims to determine the concordance of results between D-10® and Minicap Flex Piercing® and the impact of the presence of hemoglobin variants in the glycated hemoglobin assay. All the samples were assayed in parallel. The agreement between these methods was assessed using the Bland and Altman plot. We collected a total of 166 samples. In the entire study population and in patients with a hemoglobin variant, the Bland and Altman graph showed good agreement between the values (for respective biases of 0.21% and 0.29%) as well as a significant correlation (p < 0.001). Our results differ from those found by Kesso Barry et al. This difference can be explained by the high prevalence of patients with abnormal hemoglobins S and C (39.2 %) in our study population. Despite a good agreement between the methods, the results do not allow us to confirm a transferability between the two systems in diabetics and carriers of hemoglobin variants.

Notre étude vise à déterminer la concordance des résultats entre le D-10® et le Minicap Flex Piercing®, ainsi que l'impact de la présence des variants d'hémoglobine dans le dosage de l'hémoglobine glyquée. Tous les échantillons ont été dosés en parallèle sur les deux automates. L'évaluation de la concordance a été réalisée grâce au diagramme de Bland et Altman. Nous avons colligé un total de 166 échantillons. Chez l'ensemble de la population d'étude et chez les patients avec un variant d'hémoglobine, le graphique de Bland et Altman a montré une bonne concordance entre les valeurs (pour des biais respectifs de 0,21 % et 0,29 %) ainsi qu'une corrélation significative (p < 0,001). Nos résultats diffèrent de ceux trouvés par Kesso Barry et al. Cette différence peut s'expliquer par la forte prévalence de patients possédant des hémoglobines anormales S et C (39,2 %) dans notre population d'étude. Malgré une bonne concordance, nos résultats ne permettent pas d'affirmer une transférabilité entre les deux systèmes chez les diabétiques et les porteurs de variants d'hémoglobine.