Molecular Epidemiology, Drug Susceptibility and Economic Aspects of Tuberculosis in Mubende District, Uganda

Abstract

BackgroundTuberculosis (TB) remains a global public health problem whose effects have major impact in developing countries like Uganda. This study aimed at investigating genotypic characteristics and drug resistance profiles of Mycobacterium tuberculosis isolated from suspected TB patients. Furthermore, risk factors and economic burdens that could affect the current control strategies were studied.MethodsTB suspected patients were examined in a cross-sectional study at the Mubende regional referral hospital between February and July 2011. A questionnaire was administered to each patient to obtain information associated with TB prevalence. Isolates of M. tuberculosis recovered during sampling were examined for drug resistance to first line anti-TB drugs using the BACTEC-MGIT960TMsystem. All isolates were further characterized using deletion analysis, spoligotyping and MIRU-VNTR analysis. Data were analyzed using different software; MIRU-VNTR plus, SITVITWEB, BioNumerics and multivariable regression models.Results M. tuberculosis was isolated from 74 out of 344 patients, 48 of these were co-infected with HIV. Results from the questionnaire showed that previously treated TB, co-infection with HIV, cigarette smoking, and overcrowding were risk factors associated with TB, while high medical related transport bills were identified as an economic burden. Out of the 67 isolates that gave interpretable results, 23 different spoligopatterns were detected, nine of which were novel patterns. T2 with the sub types Uganda-I and Uganda-II was the most predominant lineage detected. Antibiotic resistance was detected in 19% and multidrug resistance was detected in 3% of the isolates.ConclusionThe study detected M. tuberculosis from 21% of examined TB patients, 62% of whom were also HIV positive. There is a heterogeneous pool of genotypes that circulate in this area, with the T2 lineage being the most predominant. High medical related transport bills and drug resistance could undermine the usefulness of the current TB strategic interventions.

The T2 Mycobacterium tuberculosis Genotype, Predominant in Kampala, Uganda, Shows Negative Correlation with Antituberculosis Drug Resistance

“…It can be speculated from our findings that the observed negative correlation of the predominant lineage (T2) circulating in this population might be partly responsible for the low levels of anti-TB drug resistance in Kampala as detailed in our previous report (16). Predominance of the T2 lineage has been reported from elsewhere in Uganda, where drug resistance rates were similarly low (18,19). Whether T2 is inherently less likely to become drug resistant or whether this is merely a reflection of environmental differences (for example, with regard to the quality of TB control measures) remains to be investigated.…”

“…Although 21.5% of the spoligotypes were not previously identified and the T2 lineage contributed only 45.7% of the identified isolates, we document a clear negative correlation between the T2 lineage and resistance to any of the anti-TB drugs. The T2 strains in this study belonged to SIT420, -135, -128, -125, and -52, which were previously documented to be the predominant cause of TB in Rubaga municipality and some parts of rural Uganda (17)(18)(19)24). Compared to other lineages that were distinctly identified and significantly contributed to our sample, specifically the LAM, CAS, and T1 families, T2 isolates were significantly less often an- a "Other" includes sublineages with less than 2% total contribution to the number of isolates analyzed, including undesignated, Beijing, EAI, Haarlem, MANU, S, T2T3, and T2_Eth, and spoligotypes unknown to the SITVIT database.…”

“…TB molecular analytical studies published from Uganda so far have included relatively small numbers of patients from limited administrative entities and/or a few clinics in which particular strains may predominate through localized transmission (17)(18)(19), while none have covered larger geographical areas through representative sampling. Our aim was to examine anti-TB drug resistance patterns of different MTC lineages circulating in the entire city of Kampala and to establish their relationship with HIV infection and other patient demographic characteristics in this city where the burden of TB, HIV, and TB-HIV coinfection is high.…”

A Comparison of Tools Used for Tuberculosis Diagnosis in Resource-Limited Settings: A Case Study at Mubende Referral Hospital, Uganda

“…Only TB cases caused by bacteria in the Mycobacterium tuberculosis Complex (MTC) were considered in this analysis [22], [23]. It should also be noted that DZM is the only diagnostic tool used at Mubende regional referral hospital.…”

Prime-boost vaccination with Bacillus Calmette Guerin and a recombinant adenovirus co-expressing CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium tuberculosis induces robust antigen-specific immune responses in mice

“…Due to Mtb reactivation at a latent state in immunocompromised individuals, slow progress in dealing with drug-resistant Mtb infection and the co-infection of Mtb with human immunodeficiency virus, the global burden of TB remains high, particularly in developing countries (2,3).…”