Whole-genome sequencing illuminates the evolution and spread of multidrug-resistant tuberculosis in Southwest Nigeria

• Published in: PloS one Vol. 12; no. 9; p. e0184510
• Main Authors: Senghore, Madikay, Otu, Jacob, Witney, Adam, Gehre, Florian, Doughty, Emma L, Kay, Gemma L, Butcher, Phillip, Salako, Kayode, Kehinde, Aderemi, Onyejepu, Nneka, Idigbe, Emmanuel, Corrah, Tumani, de Jong, Bouke, Pallen, Mark J, Antonio, Martin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.09.2017; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Antibiotics; Antitubercular Agents - pharmacology; Bacteria; Bacterial Proteins - genetics; Biology and Life Sciences; Cameroon - epidemiology; Child; Child, Preschool; Councils; Disease transmission; DNA Gyrase - genetics; DNA topoisomerase; Drug resistance; Drug Resistance, Multiple, Bacterial - drug effects; Drug Resistance, Multiple, Bacterial - genetics; Epidemiology; Evolution; Female; Gene sequencing; Genetics; Genome, Bacterial; Genomes; Hospitals; Humans; Infant; Infant, Newborn; Infections; Laboratories; Male; Medical research; Medicine; Medicine and Health Sciences; Multidrug resistance; Multidrug resistant organisms; Mutation; Mycobacterium tuberculosis - classification; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - isolation & purification; Nigeria - epidemiology; Pan-Africanism; Parasitology; Patients; People and Places; Phylogenetics; Phylogeny; Sequence Analysis, DNA; Tuberculosis; Tuberculosis, Multidrug-Resistant - diagnosis; Tuberculosis, Multidrug-Resistant - epidemiology; Tuberculosis, Multidrug-Resistant - microbiology; Young Adult; Nigeria; Gambia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0184510

Nigeria has an emerging problem with multidrug-resistant tuberculosis (MDR-TB). Whole-genome sequencing was used to understand the epidemiology of tuberculosis and genetics of multi-drug resistance among patients from two tertiary referral centers in Southwest Nigeria. In line with previous molecular epidemiology studies, most isolates of Mycobacterium tuberculosis from this dataset belonged to the Cameroon clade within the Euro-American lineage. Phylogenetic analysis showed this clade was undergoing clonal expansion in this region, and suggests that it was involved in community transmission of sensitive and multidrug-resistant tuberculosis. Five patients enrolled for retreatment were infected with pre-extensively drug resistant (pre-XDR) due to fluoroquinolone resistance in isolates from the Cameroon clade. In all five cases resistance was conferred through a mutation in the gyrA gene. In some patients, genomic changes occurred in bacterial isolates during the course of treatment that potentially led to decreased drug susceptibility. We conclude that inter-patient transmission of resistant isolates, principally from the Cameroon clade, contributes to the spread of MDR-TB in this setting, underscoring the urgent need to curb the spread of multi-drug resistance in this region.