Genetic variability and consequence of Mycobacterium tuberculosis lineage 3 in Kampala-Uganda

• Published in: PloS one Vol. 14; no. 9; p. e0221644
• Main Authors: Wampande, Eddie M, Naniima, Peter, Mupere, Ezekiel, Kateete, David P, Malone, LaShaunda L, Stein, Catherine M, Mayanja-Kizza, Harriet, Gagneux, Sebastien, Boom, W Henry, Joloba, Moses L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09-09-2019; Public Library of Science (PLoS)
• Subjects: Adult; Bacillus Calmette-Guerin vaccine; BCG; Biology and Life Sciences; Care and treatment; Clinical outcomes; Collaboration; Demographics; Drug resistance; Genetic aspects; Genetic diversity; Genetic polymorphisms; Genetic research; Genetic variability; Genetic Variation; Genotype; Health risks; Health sciences; HIV; Hospitals; Human immunodeficiency virus; Humans; Infectious diseases; Lung diseases; Lymphadenitis; Lymphatic diseases; Medicine and Health Sciences; Multivariate Analysis; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - physiology; Nucleotides; People and Places; Phenotype; Phenotypes; Polymorphism; Proxy; Risk analysis; Risk Factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Systematic review; Tuberculosis; Tuberculosis, Pulmonary - microbiology; Uganda; Veterinary medicine; Uganda; Asia; Switzerland; Kampala Uganda; East Africa; India
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0221644

Limited data existed exclusively describing Mycobacterium tuberculosis lineage 3 (MTB-L3), sub-lineages, and clinical manifestations in Kampala, Uganda. This study sought to elucidate the circulating MTB-L3 sub-lineages and their corresponding clinical phenotypes.
A total of 141 M. tuberculosis isolates were identified as M. tuberculosis lineage 3 using Single nucleotide polymorphism (SNP) marker analysis method. To ascertain the sub-lineages/sub-strains within the M. tuberculosis lineage 3, the direct repeat (DR) loci for all the isolates was examined for sub-lineage specific signatures as described in the SITVIT2 database. The infecting sub-strains were matched with patients' clinical and demographic characteristics to identify any possible association.
The data showed 3 sub-lineages circulating with CAS 1 Delhi accounting for 55% (77/141), followed by CAS 1-Kili 16% (22/141) and CAS 2/CAS 8% (12/141). Remaining isolates 21% (30/141) were unclassifiable. To explore whether the sub-lineages differ in their ability to cause increased severe disease, we used extent of lung involvement as a proxy for severe disease. Multivariable analysis showed no association between M. tuberculosis lineage 3 sub-lineages with severe disease. The risk factors associated with severe disease include having a positive smear (OR = 9.384; CI 95% = 2.603-33.835), HIV (OR = 0.316; CI 95% = 0.114-0.876), lymphadenitis (OR = 0. 171; CI 95% = 0.034-0.856) and a BCG scar (OR = 0.295; CI 95% = 0.102-0.854).
In Kampala, Uganda, there are three sub-lineages of M. tuberculosis lineage 3 that cause disease of comparable severity with CAS-Dehli as the most prevalent. Having HIV, lymphadenitis, a BCG scar and a smear negative status is associated with reduced severe disease.