Background Genetic polymorphisms in the human immune system modulate susceptibility to malaria. However, there is a paucity of data on the contribution of immunogenetic variants to malaria susceptibility in infants, who present differential biological features related to the immaturity of their adaptive immune system, the protective effect of maternal antibodies and fetal haemoglobin. This study investigated the association between genetic variation in innate immune response genes and malaria susceptibility during the first year of life in 656 infants from a birth cohort survey performed in Nanoro, Burkina Faso. Methods Seventeen single nucleotide polymorphisms (SNPs) in 11 genes of the immune system previously associated with different malaria phenotypes were genotyped using TaqMan allelic hybridization assays in a Fluidigm platform. Plasmodium falciparum infection and clinical disease were documented by active and passive case detection. Case–control association analyses for both alleles and genotypes were carried out using univariate and multivariate logistic regression. For cytokines showing significant SNP associations in multivariate analyses, cord blood supernatant concentrations were measured by quantitative suspension array technology (Luminex). Results Genetic variants in IL-1β (rs1143634) and FcγRIIA/CD32 (rs1801274)—both in allelic, dominant and co-dominant models—were significantly associated with protection from both P. falciparum infection and clinical malaria. Furthermore, heterozygote individuals with rs1801274 SNP in FcγRIIA/CD32 showed higher IL-1RA levels compared to wild-type homozygotes (P = 0.024), a cytokine whose production is promoted by the binding of IgG immune complexes to Fcγ receptors on effector immune cells. Conclusions These findings indicate that genetic polymorphisms in genes driving innate immune responses are associated to malaria susceptibility during the first year of life, possibly by modulating production of inflammatory mediators.

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Background Extended-spectrum β-lactamase (ESBL), plasmid-mediated AmpC-β-lactamase and carbapenemase producing Escherichia coli and Klebsiella pneumoniae have spread into environment worldwide posing a possible public health threat. However, the prevalence data in low- and middle-income countries are still scarce. The aim of this study was to assess the occurrence of ESBL, AmpC-β-lactamase and carbapenemase producing and multidrug-resistant E. coli and K. pneumoniae in wastewater collected from healthcare centers in Burkina Faso. Methodology Eighty-four (84) wastewater samples were collected from 5 healthcare centers and bacterial counts on ESBL ChromAgar were performed. E. coli and K. pneumoniae isolates were identified using API20E. ESBL production was confirmed using the double disc synergy test (DDST). AmpC-β-lactamase detection was performed on Muller Hinton (MH) agar supplemented with cloxacillin (4µg/l). Carbapenemase testing was carried out using O.K.N.V.I. RESIST-5 immunochromatography test. Result E. coli and/ or K. pneumoniae strains were isolated from 82 wastewater samples (97.6%). In total, 170 strains were isolated, E. coli more commonly (64%). Average concentrations of ESBL producing bacteria per hospital varied from 1.10x105 to 5.23x106 CFU/ml. Out of 170 presumptive ESBL producing isolates and 51 presumptive AmpC-β-lactamase producing isolates, 95% and 45% were confirmed, respectively. Carbapenemase production was detected in 10 isolates, 6 were NDM producers, 3 were OXA-48 producers and 1 was NDM and OXA-48 producer. All isolates were multidrug resistant and, furthermore, all of them were resistant to all β-lactams tested. Also, resistance to ESBL inhibitors was common, up to 66% E. coli and 62% in K. pneumoniae. Amikacin, fosfomycin and nitrofurantoin were the antibiotics for which least resistance was detected. Conclusion This study showed that wastewater from healthcare centers constitutes a reservoir of multidrug-resistant bacteria in Burkina Faso, including those capable of producing carbapenemases, which may disseminate into environment and further back to humans. Therefore, following the microbiological quality of the wastewaters released from healthcare centers is important to include in the future national AMR surveillance program.