Ezati Nicholas, Lukoye Deus, Wampande Eddie M, Musisi Kenneth, Kasule George W, Cobelens Frank G J, Kateete David P, Joloba Moses L
National Tuberculosis and Leprosy Program, Kampala, Uganda.
Department of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda.
BMC Infect Dis. 2014 Dec 19;14:703. doi: 10.1186/s12879-014-0703-0.
The 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.
We 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.
Out 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 (OR(adj) =2.9; 95% CI 1.63-5.06; p = 0.001) or MDR (OR(adj) 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.
The 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.
耐多药结核病（MDR-TB）全球负担的增加凸显了迫切需要获取有关结核病耐药性产生和传播相关因素的数据。我们对结核分枝杆菌（MTB）分离株的代表性样本进行了分子分析。基于坎帕拉分子流行病学研究的结果，我们假设乌干达主要的MTB菌株谱系与抗结核药物耐药性呈负相关，并着手检验这一假设。
我们从全国结核病耐药性调查中涂片阳性结核病患者收集的分枝杆菌分离株中提取DNA，并进行IS6110-PCR。为了鉴定MTB谱系/亚谱系，使用特异性引物和杂交探针进行RT-PCR SNP，并进行“熔解曲线”分析以区分乌干达II家族与其他MTB家族。主要结局是乌干达II家族的分布及其与抗结核药物耐药性和HIV感染的关联。
在纳入的1537例患者中，有1001例患者的MTB分离株可用于SNP分析以鉴定乌干达II家族，其中973例（97%）有明确的RT-PCR结果。在这些患者中，422例（43.4%）属于乌干达II家族，主要分布在西南地区（55.0%；与其他地区相比OR = 4.6；95%CI 2.83 - 7.57；p < 0.001），但在其他七个地理区域也有不同程度的分布。与乌干达II家族相比，其他基因型作为一个整体更有可能对任何抗结核药物耐药（校正后OR = 2.9；95%CI 1.63 - 5.06；p = 0.001）或耐多药（校正后OR 4.9；95%CI，1.15 - 20.60；p = 0.032），即使在对地理区域、患者类别、性别、居住地和HIV状态进行校正之后。在25 - 34岁年龄组中最为常见，为159/330（48.2%）。未观察到乌干达II家族与HIV感染之间存在关联。
乌干达II家族是乌干达所有全国结核病防治规划地区结核病发病的主要原因。与其他MTB菌株谱系相比，其对抗结核药物耐药的可能性较小。
