Molecular epidemiology and drug resistance of Mycobacterium tuberculosis isolates from Ethiopian pulmonary tuberculosis patients with and without human immunodeficiency virus infection

Abstract

We have analyzed the molecular epidemiology and drug resistance of 121 Mycobacterium tuberculosis isolates from consecutive patients with culture-positive pulmonary tuberculosis attending a university hospital outpatient department in Addis Ababa, Ethiopia. Restriction fragment length polymorphism analysis and spoligotyping were used to analyze the DNA fingerprinting patterns. Fifty-one (41.2%) of the isolates were found in 13 clusters with two or more identical DNA patterns. Two such clusters contained 49.0% of all clustered isolates. In a multivariate logistic regression model, human immunodeficiency virus (HIV)-positive serostatus was significantly associated with clustering of isolates for patients of both sexes (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.17 to 5.80). There was a trend toward increased clustering of isolates from tuberculous women residing in Addis Ababa (OR, 2.10; 95% CI, 0.85 to 5.25). In total, 17 of 121 isolates (14.0%) were resistant to one or more of the antituberculosis drugs isoniazid (8.3%), streptomycin (7.4%), rifampin (2.5%), and ethambutol (1.7%). The high rate of drug-resistant isolates (29.6%) coincided with the peak prevalence of HIV infection (77.8%) in patients 35 to 44 years old. The majority (62.5%) of resistant isolates in this group were found within clusters. The simultaneous accumulation of certain bacterial clones in a patient population likely reflects recent transmission. Hence, we conclude that tuberculosis is commonly caused by recent infection with M. tuberculosis in HIV-positive Ethiopian patients. Furthermore, with the rapidly increasing prevalence of HIV infection in Ethiopia, the burden of tuberculosis, including drug-resistant tuberculosis, is likely to increase. Strengthening of classical tuberculosis control measures by promoting active case finding among HIV-positive adults with tuberculosis is warranted to reduce rates of transmission.

FIG. 1.

Prevalence of HIV infection and overall drug resistance among Ethiopian patients with pulmonary TB stratified by age group.

FIG. 2.

IS6110 banding patterns and similarity matrices for 121 M. tuberculosis isolates from Ethiopian patients with pulmonary TB. Banding patterns are ordered by similarity. The corresponding dendrograms are to the left of the panels. The positions of the bands in each lane are adjusted (normalized) so that the band positions for all strains are comparable. The scale depicts similarity coefficients (which are defined elsewhere [37]).

FIG. 3.

Schematic representation of the spoligotypes of M. tuberculosis isolates belonging to four clusters with less than five bands by RFLP analysis of IS6110 (Fig. 2) compared with the spoligotypes of reference strains H37RV and M. bovis BCG. The filled rectangles depict positive hybridization signals, and empty rectangles represent a lack of hybridization.