Pro‐inflammatory cytokines induced by glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum contribute to malaria pathogenesis and hence, the naturally acquired anti‐GPI antibody thought to provide protection against severe malaria (SM) by neutralizing the stimulatory activity of GPIs. In previous studies, the anti‐GPI antibody levels increased with age in parallel with the development of acquired immunity, and high levels of anti‐GPI antibodies were associated with mild malaria (MM) cases. In the present study, the relationship between the levels of pro‐inflammatory cytokines and anti‐GPI IgG antibody responses, parasitemia, and the clinical outcomes were evaluated in SM and mild malaria (MM) patients. Sera from a total of 110 SM and 72 MM cases after excluding of ineligible patients were analyzed for the levels of anti‐GPI antibodies, IgG subclasses, and cytokine responses by ELISA. While the total anti‐GPI antibody levels were similar in overall SM and MM groups, they were significantly higher in surviving SM patients than in fatal SM cases. In the case of cytokines, the TNF‐α and IL‐6 levels were significantly higher in SM compared to MM, whereas the IL‐10 levels were similar in both groups. The data presented here demonstrate that high levels of the circulatory pro‐inflammatory, TNF‐α, and IL‐6, are indicators of malaria severity, whereas anti‐inflammatory cytokine IL‐10 level does not differentiate SM and MM cases. Further, among SM patients, relatively low levels of anti‐GPI antibodies are indicators of fatal outcomes compared to survivors, suggesting that anti‐GPI antibodies provide some level of protection against SM fatality.

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Telemedicine is considered to be an effective strategy to aid in the recruitment and retention of physicians in underserved areas and, in doing so, improve access to healthcare. Telemedicine’s use, however, depends on individual and contextual factors. Using a mixed methods design, we studied these factors in Senegal based on a micro, meso and macro framework. A quantitative questionnaire administered to 165 physicians working in public hospitals and 151 physicians working in district health centres was used to identify individual (micro) factors. This was augmented with qualitative descriptive data involving individual interviews with 30 physicians working in public hospitals, 36 physicians working in district health centres and 10 telemedicine project managers to identify contextual (meso and macro) factors. Physicians were selected using purposeful random sampling; managers through snowball sampling. Quantitative data were analyzed descriptively using SPSS 23 and qualitative data thematically using NVivo 10. At the micro level, we found that 72.1% of the physicians working in public hospitals and 82.1% of the physicians working in district health centres were likely to use telemedicine in their professional activities. At the meso level, we identified several technical, organizational and ethical factors, while at the macro level the study revealed a number of financial, political, legal, socioeconomic and cultural factors. We conclude that better awareness of the interplay between factors can assist health authorities to develop telemedicine in ways that will attract use by physicians, thus improving physicians’ recruitment and retention in underserved areas.

BRCA1 and BRCA2 are the most incriminated genes in inherited breast/ovarian cancers. Several pathogenic variants of these genes conferring genetic predisposition have been described in different populations but rarely in sub-Saharan Africa. The objectives of this study were to identify pathogenic variants of the BRCA genes involved in hereditary breast cancer in Senegal and to search for a founder effect. We recruited after free informed consent, 27 unrelated index cases diagnosed with breast cancer and each having a family history. Mutation screening of the genes identified a duplication of ten nucleotides c.815_824dupAGCCATGTGG, (p. Thr276Alafs) (NM_007294.3) located in exon 11 of BRCA1 gene, in 15 index cases (allelic frequency 27.7%). The pathogenic variant has been previously reported in African Americans as a founder mutation of West African origin. Haplotypes analysis of seven microsatellites surrounding the BRCA1 gene highlights a shared haplotype encompassing~400 kb between D17S855 and D17S1325. This haplotype was not detected in none of 15 healthy controls. Estimation of the age of the pathogenic variant suggested that it occurred~1400 years ago. Our study identified a founder pathogenic variant of BRCA1 predisposing to breast cancer and enabled the establishment of an affordable genetic test as a mean of prevention for Senegalese women at risk.npj Genomic Medicine (2020) 5:8 ; https://doi.

Merozoite surface proteins (MSPs) are critical for parasite invasion; they represent attractive targets for antibody-based protection against clinical malaria. To identify protection-associated target MSPs, the present study analysed antibody responses to whole merozoite extract (ME) and to defined MSP recombinant antigens in hospitalized patients from a low endemic urban area as a function of disease severity (mild versus cerebral malaria). Sera from 110 patients with confirmed severe cerebral malaria (CM) and 91 patients with mild malaria (MM) were analysed (mean age = 29 years) for total and subclass immunoglobulin (Ig)G to ME and total IgG to MSP1p19, MSP2, MSP3, MSP4 and MSP5 by enzyme-linked immunosorbent assay (ELISA). Functional antibody responses were evaluated using the antibody-dependent respiratory burst (ADRB) assay in a subset of sera. There was a trend towards higher IgG1 and IgG4 levels to ME in CM compared to MM; only ME IgM responses differed significantly between fatal and surviving CM patients. Increased prevalence of IgG to individual MSPs was found in the CM compared to the MM group, including significantly higher levels of IgG to MSP4 and MSP5 in the former. Sera from fatal (24·5%) versus surviving cases showed significantly lower IgG to MSP1p19 and MSP3 (P < 0·05). ADRB assay readouts correlated with high levels of anti-MSP IgG, and trended higher in sera from patients with surviving compared to fatal CM outcome (P = 0·07). These results document strong differential antibody responses to MSP antigens as targets of protective immunity against CM and in particular MSP1p19 and MSP3 as prognostic indicators.