BackgroundDrug resistance among tuberculosis patients in sub-Saharan Africa is increasing, possibly due to association with HIV infection. We studied drug resistance and HIV infection in a representative sample of 533 smear-positive tuberculosis patients diagnosed in Kampala, Uganda.Methods/Principal FindingsAmong 473 new patients, multidrug resistance was found in 5 (1.1%, 95% CI 0.3–2.5) and resistance to any drug in 57 (12.1%, 9.3–15.3). Among 60 previously treated patients this was 7 (11.7%, 4.8–22.6) and 17 (28.3%; 17.5–41.4), respectively. Of 517 patients with HIV results, 165 (31.9%, 27.9–36.1) tested positive. Neither multidrug (adjusted odds ratio (ORadj) 0.7; 95% CI 0.19–2.6) nor any resistance (ORadj 0.7; 0.43–1.3) was associated with HIV status. Primary resistance to any drug was more common among patients who had worked in health care (ORadj 3.5; 1.0–12.0).Conclusion/SignificanceAnti-tuberculosis drug resistance rates in Kampala are low and not associated with HIV infection, but may be associated with exposure during health care.

Background: Drug resistance is a challenge for the global control of tuberculosis. We examined mortality in tuberculosis patients from high-burden countries, according to concordance or discordance of results from drug susceptibility testing (DST) done locally and in a reference laboratory. Methods: We collected Mycobacterium tuberculosis isolates from adult patients in Côte d’Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand, stratified by HIV status and tuberculosis drug resistance. Molecular or phenotypic drug susceptibility testing (DST) was done locally and at the Swiss tuberculosis reference laboratory. We examined mortality during treatment according to DST results and treatment adequacy in logistic regression models adjusting for sex, age, sputum microscopy and HIV status. Findings: 634 tuberculosis patients were included; median age was 33.2 years, 239 (37.7%) were female, 272 (42.9%) HIV-positive and 69 (10.9%) patients died. Based on the reference laboratory DST, 394 (62.2%) strains were pan-susceptible, 45 (7.1%) mono-resistant, 163 (25.7%) multidrug-resistant (MDR-TB), and 30 (4.7%) had pre-extensive or extensive drug resistance (pre-XDR/XDR-TB). Results of reference and local laboratories were discordant in 121 (19.1%) cases. Overall, sensitivity and specificity to detect any resistance were 90.8% and 84.3%, respectively. Mortality ranged from 6.0% (20/336) in patients with pan-susceptible tuberculosis treated according to WHO guidelines to 57.1% (8/14) in patients with resistant strains who were under treated. In logistic regression, compared to concordant DST results, the adjusted odds ratio of death was 7.33 (95% CI 2.70–19.95) for patients with discordant results potentially leading to under treatment. Interpretation: Inaccurate DST by comparison to a reference standard led to under treatment of drug resistant tuberculosis and increased mortality. Rapid molecular DST of first- and second-line drugs at diagnosis is required to improve outcomes in patients with MDR-TB and pre-XDR/XDR-TB.

Objective. Data on pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) complex in Nigeria are limited. We investigated species of MTB complex in TB cases from northern Nigeria. Methods. New TB suspects were enrolled, screened for HIV and their sputum samples were cultured after routine microscopy. Genotypes MTBC and MTBDRplus were used to characterize the MTB complex species and their resistance to isoniazid and rifampicin. Results. Of the 1,603 patients enrolled, 375 (23%) had MTB complex infection: 354 (94.4%) had Mycobacterium tuberculosis; 20 (5.3%) had Mycobacterium africanum; and one had Mycobacterium bovis (0.3%). Cases were more likely to be male (AOR = 1.87, 95% CI : 1.42–2.46; P ≤ 0.001), young (AOR = 2.03, 95% CI : 1.56–2.65; P ≤ 0.001) and have HIV (AOR = 1.43, 95% CI : 1.06–1.92; P = 0.032). In 23 patients (6.1%), the mycobacterium was resistant to at least one drug, and these cases were more likely to have HIV and prior TB treatment (AOR = 3.62, 95% CI : 1.51–8.84; P = 0.004; AOR : 4.43; 95% CI : 1.71–11.45 P = 0.002 resp.), compared to cases without any resistance. Conclusion. Mycobacterium tuberculosis remained the predominant specie in TB in this setting followed by Mycobacterium africanum while Mycobacterium bovis was rare. The association of TB drug resistance with HIV has implications for TB treatment.

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.