RESUMO
The MORDOR I trial1, conducted in Niger, Malawi and Tanzania, demonstrated that mass azithromycin distribution to preschool children reduced childhood mortality1. However, the large but simple trial design precluded determination of the mechanisms involved. Here we examined the gut microbiome of preschool children from 30 Nigerien communities randomized to either biannual azithromycin or placebo. Gut microbiome γ-diversity was not significantly altered (P = 0.08), but the relative abundances of two Campylobacter species, along with another 33 gut bacteria, were significantly reduced in children treated with azithromycin at the 24-month follow-up. Metagenomic analysis revealed functional differences in gut bacteria between treatment groups. Resistome analysis showed an increase in macrolide resistance gene expression in gut microbiota in communities treated with azithromycin (P = 0.004). These results suggest that prolonged mass azithromycin distribution to reduce childhood mortality reduces certain gut bacteria, including known pathogens, while selecting for antibiotic resistance.
Assuntos
Azitromicina/administração & dosagem , Infecções por Campylobacter/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Metagenômica , Campylobacter/efeitos dos fármacos , Campylobacter/patogenicidade , Infecções por Campylobacter/genética , Infecções por Campylobacter/mortalidade , Criança , Mortalidade da Criança , Pré-Escolar , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Humanos , Macrolídeos/administração & dosagem , Masculino , Nigéria/epidemiologia , Análise de Sequência de RNARESUMO
To analyze the determinants of the persistence of the cholera epidemic in Tillabery to obtain a durable solution. Case-control study conducted in three health centers in June 2013 in Tillabery. Cholera cases were confirmed by laboratory testing or epidemiologically linked with a confirmed index case. Controls were individuals with no history of diarrhea, of the same sex, from the same village and with an age difference that did not exceed five years. A logistic regression model was used to analyze the appearance of cholera according to the determining factors. The analysis showed significant association between the occurrence of cholera and variables related to behavior. The adjusted OR confirm higher risks of cholera for persons in households with more than five inhabitants (crude OR = 1.55 95 % CI (1.06 to 2.28) and adjusted OR 95 % CI 2.68 (1.79 to 4.56)), or in contact with a person with diarrhea (crude OR = 1.86 95% CI (1.26 to 2.75) and adjusted OR = 1.61 95% CI (1.5 to 2.68)), and who report not washing their hands after defecation (crude OR = 3.44 95% CI (2.20 to 5.41) and adjusted OR = 2.76 95% CI (1.73 to 3.79)). This study concludes that the Tillabery cholera victims are primarily those with hazardous hygienic practices. Niger must define operational recommendations to limit the continuance of cholera in certain river areas, particularly in the Tillabery.