The Mycobacterium tuberculosisUganda II family and resistance to first-line anti-tuberculosis drugs in Uganda

Abstract

BackgroundThe global increase in the burden of multidrug-resistant tuberculosis (MDR-TB) underscores an urgent need for data on factors involved in generation and spread of TB drug resistance. We performed molecular analyses on a representative sample of Mycobacterium tuberculosis (MTB) isolates. Basing on findings of the molecular epidemiological study in Kampala, we hypothesized that the predominant MTB strain lineage in Uganda is negatively associated with anti-TB drug resistance and we set out to test this hypothesis.MethodsWe extracted DNA from mycobacterial isolates collected from smear-positive TB patients in the national TB drug resistance survey and carried out IS6110-PCR. To identify MTB lineages/sub lineages RT-PCR SNP was performed using specific primers and hybridization probes and the ‘melting curve’ analysis was done to distinguish the Uganda II family from other MTB families. The primary outcome was the distribution of the Uganda II family and its associations with anti-TB drug resistance and HIV infection.ResultsOut of the 1537 patients enrolled, MTB isolates for 1001 patients were available for SNP analysis for identification of Uganda II family, of which 973 (97%) had conclusive RT-PCR results. Of these 422 (43.4%) were of the Uganda II family, mostly distributed in the south west zone (55.0%; OR = 4.6 for comparison with other zones; 95% CI 2.83-7.57; p < 0.001) but occurred in each of the other seven geographic zones at varying levels. Compared to the Uganda II family, other genotypes as a group were more likely to be resistant to any anti-TB drug (ORadj =2.9; 95% CI 1.63-5.06; p = 0.001) or MDR (ORadj 4.9; 95% CI, 1.15-20.60; p = 0.032), even after adjusting for geographic zone, patient category, sex, residence and HIV status. It was commonest in the 25–34 year age group 159/330 (48.2%). No association was observed between Uganda II family and HIV infection.ConclusionThe Uganda II family is a major cause of morbidity due to TB in all NTLP zones in Uganda. It is less likely to be resistant to anti-TB drugs than other MTB strain lineages.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0703-0) contains supplementary material, which is available to authorized users.

Resistance of Mycobacterium tuberculosis strains to Rifampicin: A systematic review and meta-analysis

“…The prevelance of rifampicin resistance non-Beijing families were less than 6% and were found in all WHO Regions. For instance, resistance Haarlem family was reported from Region of American, South-East Asia and European Region [17, 23, 28], CAS reported from South-East Asia, European and African Region and EAI and T families were reported from Western Pacific, South-East Asia, European and African Region [25, 29, 33, 39]. Ural was the only strain reported from East Medterranian Region, in Iran as rifampicin resistance, but it was identfed in South-East Asia, India and Region of American, Brazil, with low prevelance [15].…”

Prevalence and patterns of rifampicin and isoniazid resistance conferring mutations in Mycobacterium tuberculosis isolates from Uganda

“…tuberculosis sub-lineage Uganda strains that are predominant in Uganda explains the previously reported weak association between MDR-TB and M . tuberculosis Uganda genotype [ 28 , 29 ].…”

Mycobacterium tuberculosis Uganda II is more susceptible to rifampicin and isoniazid compared to Beijing and Delhi/CAS families

“…We have investigated drug-resistance and virulence as factors associated with the predominance of the M. tuberculosis Uganda family in Uganda. In one of the studies, we found that the M. tuberculosis Uganda family is three times less likely to be resistant to first-line anti-TB drugs and five times less likely to be multidrug resistant, compared to the non-Uganda II families [ 5 ]. Furthermore, in the other study investigating virulence we found that the M. tuberculosis Uganda family was less virulent as defined by cavitary disease [ 8 ].…”

“…M. tuberculosis Uganda is a sub-lineage of the M. tuberculosis lineage 4, the Euro- American lineage which is defined by RD 724 deletion [ 4 – 8 ]. The M. tuberculosis Uganda family comprises M. tuberculosis Uganda I and Uganda II subfamilies with the latter being more prevalent in Uganda [ 5 , 7 ]. Asiimwe et al, 2008 [ 4 ], Nabyonga et al, 2011 [ 7 ], and more recently Ezati et al, 2014 [ 5 ], reported higher occurrence in Uganda of the M. tuberculosis Uganda subfamily (>70 %) compared with other genotypes combined (LAM, Delhi/CAS and Beijing families about 3 % each).…”