Genetic diversity and drug resistance profiles of Mycobacterium tuberculosis complex isolates from patients with extrapulmonary tuberculosis in Ghana and their associated host immune responses

Samuel Ofori Addo; Gloria Ivy Mensah; Lydia Mosi; Afua Owusua Darkwah Abrahams; Kennedy Kwasi Addo

doi:10.1016/j.ijregi.2022.06.005

Genetic diversity and drug resistance profiles of Mycobacterium tuberculosis complex isolates from patients with extrapulmonary tuberculosis in Ghana and their associated host immune responses

IJID Reg. 2022 Jun 27:4:75-84. doi: 10.1016/j.ijregi.2022.06.005. eCollection 2022 Sep.

Authors

Samuel Ofori Addo^{1

2

3}, Gloria Ivy Mensah¹, Lydia Mosi^{2

3}, Afua Owusua Darkwah Abrahams⁴, Kennedy Kwasi Addo¹

Affiliations

¹ Department of Bacteriology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
² Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Legon, Ghana.
³ West African Center for Cell Biology of Infectious Pathogens, College of Basic and Applied Sciences, University of Ghana, Legon, Ghana.
⁴ Department of Pathology, University of Ghana Medical School, College of Health Sciences, University of Ghana, Legon, Ghana.

Abstract

Objectives: This study sought to determine the genetic diversity and drug resistance profiles of Mycobacterium tuberculosis complex (MTBC) isolates from extrapulmonary tuberculosis (EPTB) patients in Ghana, and their associated immune responses.

Methods: Spoligotyping was performed on 102 MTBC isolates from EPTB patients. Lineages/sub-lineages were assigned by comparing spoligotyping patterns primarily with the SITVIT2 database and subsequently with the TB-Lineage online tool for unknown isolates in SITVIT2. Drug susceptibility testing was performed using MGIT (BD BACTEC 960), Lowenstein-Jensen media (indirect proportion method), and GenoType MTBDRplus/MTBDRsl assays. Differential cytokine levels in the serum of 20 EPTB patients infected with MTBC lineage 4 were determined using the Luminex multiplex immunoassay.

Results: Around 95% (97/102) of isolates were Mycobacterium tuberculosis, predominantly lineage 4 (95%; 92/97). Of the lineage 4 isolates, the majority were sub-lineage Cameroon (37%, 34/92). Prevalence was significantly higher in the 15-34 years age group among EPTB patients infected with lineage 4 strains (p = 0.024). Fifteen isolates were resistant to at least one anti-TB drug tested. Decreased levels of IL-1β, IL-17A, and IFN-α were observed in individuals infected with Cameroon sub-lineages compared with other lineage 4 sub-lineages.

Conclusions: Our study confirms Cameroon (SIT61) as the most common spoligotype causing human EPTB in Ghana, and that it is associated with decreased serum IL-1β, IL-17A, and IFN-α.

Keywords: Extrapulmonary TB; Ghana; Luminex immunoassay; Multidrug resistance; Spoligotyping.