DETERMINATION OF MULTIDRUG-RESISTANT PULMONARY TUBERCULOSIS AMONG HUMAN IMMUNUDEFICIENCY VIRUS SEROPOSISTIVE PATIENTS IN RIVERS STATE USING LINE PROBE TECHNOLOGY

Abstract

Background: Tuberculosis (TB) poses a serious health problem worldwide with a high mortality rate, especially in immunocompromised individuals. The emergence of drug-resistant forms of tuberculosis in many parts of the world is threatening to make this important human disease difficult to treat. Nigeria is currently ranked 10th among the 22 high TB burden countries, information on drug resistant tuberculosis is sparse from Rivers State.
Objective: This study was carried out to determine Mycobacterium tuberculosis (MTB) resistance pattern to first-line anti-TB drugs {rifampicin (RIF) and isoniazid (INH)} in TB patients who were HIV seropositive in Rivers State, using Line Probe Assay (LPA).
Methods: Two hundred and sixty HIV sero-positive patients ≥ 18 years old were recruited into the study. The subjects were separated into two groups: Group A consisted of previously diagnosed TB/HIV coinfected patients who were already on anti-tuberculosis treatment and Group B consisted of HIV seropositive patients, suspected of having tuberculosis who were treatment naïve. Patients’ biodata, socio-demographic data and medical risks were obtained using questionnaires. Duplicate sputum samples were collected in sterile, wide-mouthed bottles from study subjects. Direct acid fast bacilli (AFB) microscopy using Ziehl Neelsen (ZN) staining was performed. Genotypic drug susceptibility testing was performed using line probe assay (LPA). LPA indeterminate samples were subjected to culture and drug susceptibility testing by proportion method. Descriptive analysis of discrete and continuous variables as well as multivariate analysis to determine association of risk factors and the occurrence of drug resistance were carried out. Data was analyzed using the SPSS v20 software at a 95% confidence interval and a p-value of ≤ 0.05 was considered significant.
Results: Of the 260 recruited HIV seropositive subjects, 159 were positive for Mycobacterium tuberculosis, 7 were non tuberculous mycobacteria and 2 were inconclusive. MDR-TB was detected in 10.1% (16/159) of all TB/HIV coinfected subjects, 11.0% (14/127) of the study subjects undergoing treatment and 6.3% (2/32) of treatment naïve subjects. The major gene mutations conferring resistance to rifampicin occurred at codons 530-533 (∆WT8) 88.2% (15/17) and S531L 66.7% (10/15) of the rpoB gene while that for INH resistance occurred at codon S315T1 79.2% (19/24) of the katG gene. Logistic regression analysis for TB patients showed a significant association between previous exposure to anti-TB treatment and MDR-TB (OR=8.5, p=0.003) as well as RIF-monoresistant TB (3.7, p=0.02).
Conclusion: The study showed a high prevalence of MDR-TB in TB patients who were HIV coinfected in Rivers State. A high prevalence of MDR-TB was also observed in the treatment naïve subjects, suggesting primary infection, transmitted from acquired drug resistant strains. The molecular LPA technique had an important diagnostic value in smear negative cases.
The National TB Programme should be strengthened to cope with the increasing number of MDRTB in TB/HIV co-infected cases.

DETERMINATION OF MULTIDRUG-RESISTANT PULMONARY TUBERCULOSIS AMONG HUMAN IMMUNUDEFICIENCY VIRUS SEROPOSISTIVE PATIENTS IN RIVERS STATE USING LINE PROBE TECHNOLOGY