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


Autoři: Eddie M. Wampande aff001;  Peter Naniima aff001;  Ezekiel Mupere aff003;  David P. Kateete aff001;  LaShaunda L. Malone aff004;  Catherine M. Stein aff005;  Harriet Mayanja-Kizza aff004;  Sebastien Gagneux aff007;  W. Henry Boom aff005;  Moses L. Joloba aff001
Působiště autorů: Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala, Uganda aff001;  Department of Veterinary Medicine, Clinical and Comparative medicine, College of Veterinary Medicine, Animal Resources and Bio Security, Makerere University, Kampala, Uganda aff002;  Department of Pediatrics and Child Health College of Health Sciences, Makerere University, Kampala, Uganda aff003;  Uganda-Case Western Reserve University Research Collaboration, Kampala, Uganda aff004;  Tuberculosis Research Unit, School of Medicine, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, Uinted States of America aff005;  Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, Uinted States of America aff006;  Swiss Tropical and Public Health Institute, Basel, Switzerland aff007;  University of Basel, Basel, Switzerland aff008
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0221644

Souhrn

Background

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.

Method

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.

Result

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).

Conclusion

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.

Klíčová slova:

Biology and life sciences – Organisms – Bacteria – Actinobacteria – Mycobacterium tuberculosis – Viruses – RNA viruses – Microbiology – Medical microbiology – Microbial pathogens – Viral pathogens – Immunodeficiency viruses – HIV – Retroviruses – Lentivirus – Anatomy – Body fluids – Blood – Physiology – Physiological processes – Coughing – Medicine and health sciences – Infectious diseases – Bacterial diseases – Tuberculosis – Extensively drug-resistant tuberculosis – Tropical diseases – Pathology and laboratory medicine – Pathogens – Epidemiology – Medical risk factors – Diagnostic medicine – Signs and symptoms – People and places – Geographical locations – Africa – Uganda


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