Mycobacterium tuberculosis spoligotypes and drug susceptibility pattern of isolates from tuberculosis patients in South-Western Uganda

Abstract

BackgroundDetermination of the prevalence and drug susceptibility of the M. tuberculosis strains is important in tuberculosis control. We determined the genetic diversity and susceptibility profiles of mycobacteria isolated from tuberculosis patients in Mbarara, South Western Uganda.MethodsWe enrolled, consecutively; all newly diagnosed and previously treated smear-positive TB patients aged ≥ 18 years. The isolates were characterized using regions of difference (RD) analysis and spoligotyping. Drug resistance against rifampicin and isoniazid were tested using the Genotype® MDRTBplus assay and the indirect proportion method on Lowenstein-Jensen media. HIV-1 testing was performed using two rapid HIV tests.ResultsA total of 125 isolates from 167 TB suspects (60% males) with a mean age 33.7 years and HIV prevalence of 67.9% (55/81) were analyzed. Majority (92.8%) were new cases while only 7.2% were retreatment cases. All the 125 isolates were identified as M. tuberculosis strict sense with the majority (92.8%) of the isolates being modern strains while seven (7.2%) isolates were ancestral strains. Spoligotyping revealed 79 spoligotype patterns, with an overall diversity of 63.2%. Sixty two (49.6%) of the isolates formed 16 clusters consisting of 2-15 isolates each. A majority (59.2%) of the isolates belong to the Uganda genotype group of strains. The major shared spoligotypes in our sample were SIT 135 (T2-Uganda) with 15 isolates and SIT 128 (T2) with 3 isolates. Sixty nine (87%) of the 79 patterns had not yet been defined in the SpolDB4.0.database. Resistance mutations to either RIF or INH were detected in 6.4% of the isolates. Multidrug resistance, INH and RIF resistance was 1.6%, 3.2% and 4.8%, respectively. The rpoβ gene mutations seen in the sample were D516V, S531L, H526Y H526D and D516V, while one strain had a Δ1 mutation in the wild type probes. There were three strains with katG (codon 315) gene mutations only while one strain showed the inhA promoter gene mutation.ConclusionThe present study shows that the TB epidemic in Mbarara is caused by modern M. tuberculosis strains mainly belonging to the Uganda genotype and anti-TB drug resistance rate in the region is low.

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 First Insight into the Genetic Diversity and Drug Susceptibility Pattern of Mycobacterium tuberculosis Complex in Zhejiang, China

“…Different non-Beijing sublineages exhibit diverse correlation with drug susceptibility, even within the same sublineage. A recent study from Lukoye et al has revealed that the T2 MTB genotype is associated with anti-TB drug resistance [36], whereas T2 family strains isolated from Uganda has no statistical relation with anti-TB drug resistance [37]. We hypothesize that this difference is due to the poor discriminatory power of spoligotyping.…”

Clinico-pathological features of tuberculosis due to mycobacterium tuberculosis Uganda genotype in patients with tuberculous lymphadenitis: a cross sectional study

“…tuberculosis Uganda genotype causes up to 70% of pulmonary TB in Kampala [14], and other districts of Uganda [15,16]. The Uganda genotype as cause of other disease manifestations has however not been studied.…”