Kasule George W, Kateete David P, Joloba Moses L
National Tuberculosis and Leprosy Program, Kampala, Uganda.
National TB Reference Laboratory, Kampala, Uganda.
BMC Infect Dis. 2016 Apr 21;16:173. doi: 10.1186/s12879-016-1487-1.
Mycobacterium tuberculosis Uganda family is the predominant cause of tuberculosis in Uganda. Reasons for this are not clear but are likely to be due to the rampant person-to-person transmission or delayed susceptibility of the organism to drugs during treatment, which may lead to continuous shedding of infectious bacilli, among others. The objective of this study was to determine in vitro, the susceptibility patterns of M. tuberculosis Uganda family compared with Beijing and Delhi/CAS, other M. tuberculosis sub-lineages that also circulate in Uganda but are not as prevalent. The comparisons were made after 10 days of exposure of the strains to Rifampicin and Isoniazid, the most important first-line anti-tuberculosis drugs.
Minimum inhibitory concentrations (MICs) for three Isoniazid- and Rifampicin-susceptible M. tuberculosis strains (Uganda II, Beijing and Delhi/CAS families) were determined by micro-dilution plate assay. Killing curves for each strain were deduced from colony forming units after exposure to Isoniazid and Rifampicin on days 0, 2, 4, 6, 8, and 10 under aerobic and oxygen-depleted conditions. Data were analyzed with GraphPad Prism 5 software.
The MIC for Isoniazid was 0.05 μg/ml for M. tuberculosis Uganda II, and 0.03 μg/ml for M. tuberculosis Beijing and Delhi/CAS. Rifampicin MIC was 1 μg/ml for M. tuberculosis Uganda II, and 0.12 μg/ml for Beijing and Delhi/CAS. At low Rifampicin (0.03-2.5 μg/ml) and Isoniazid (0.12-5 μg/ml) concentrations under aerobic conditions, there was no significant difference in susceptibility patterns between M. tuberculosis Uganda II and Beijing or Delhi/CAS. However, at high Rifampicin (5 μg/ml) and Isoniazid (1.25 μg/ml) concentrations under oxygen-depleted conditions, M. tuberculosis Uganda II was more susceptible to the drugs compared with Beijing or Delhi/CAS families.
The predominance of M. tuberculosis Uganda II family as the main causative agent of tuberculosis in Uganda is not attributed to its susceptibility behavior to Isoniazid and Rifampicin. Probably, its predominance is due to differences in the immune defenses in the general population against the strains, given that Beijing and Delhi/CAS families may have been introduced more recently. Further research beyond susceptibility to anti-tuberculosis drugs is required to fully explore tuberculosis strain predominance in Uganda.
乌干达结核分枝杆菌家族是乌干达结核病的主要病因。其原因尚不清楚，但可能是由于人际传播猖獗，或该病原体在治疗期间对药物的敏感性延迟，这可能导致传染性杆菌持续排出等。本研究的目的是在体外确定乌干达结核分枝杆菌家族与北京和德里/CAS分枝杆菌的药敏模式，北京和德里/CAS分枝杆菌是在乌干达也有传播但不如乌干达结核分枝杆菌家族普遍的其他结核分枝杆菌亚谱系。在菌株暴露于利福平（最重要的一线抗结核药物）和异烟肼10天后进行比较。
通过微量稀释平板法测定三株对异烟肼和利福平敏感的结核分枝杆菌菌株（乌干达II型、北京型和德里/CAS型）的最低抑菌浓度（MIC）。在有氧和缺氧条件下，在第0、2、4、6、8和10天暴露于异烟肼和利福平后，根据菌落形成单位推导出每种菌株的杀菌曲线。数据用GraphPad Prism 5软件进行分析。
乌干达II型结核分枝杆菌对异烟肼的MIC为0.05μg/ml，北京型和德里/CAS型结核分枝杆菌对异烟肼的MIC为0.03μg/ml。乌干达II型结核分枝杆菌对利福平的MIC为1μg/ml，北京型和德里/CAS型结核分枝杆菌对利福平的MIC为0.12μg/ml。在有氧条件下低浓度利福平（0.03 - 2.5μg/ml）和异烟肼（0.12 - 5μg/ml）时，乌干达II型结核分枝杆菌与北京型或德里/CAS型结核分枝杆菌的药敏模式无显著差异。然而，在缺氧条件下高浓度利福平（5μg/ml）和异烟肼（1.25μg/ml）时，与北京型或德里/CAS型结核分枝杆菌家族相比，乌干达II型结核分枝杆菌对这些药物更敏感。
乌干达II型结核分枝杆菌家族作为乌干达结核病主要病原体的优势地位并非归因于其对异烟肼和利福平的药敏行为。其优势地位可能是由于普通人群对这些菌株的免疫防御存在差异，因为北京型和德里/CAS型结核分枝杆菌家族可能是较近期传入的。需要开展除抗结核药物敏感性之外的进一步研究，以充分探究乌干达结核菌株优势地位的原因。
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