Background Evidence describing the impact of diabetes mellitus (DM) on the recurrence and mutation rate of Mycobacterium tuberculosis (Mtb) is limited. Methods This study was nested in 3 cohort studies of tuberculosis (TB) patients with and without DM in India. Paired Mtb isolates recovered at baseline and treatment failure/recurrence underwent whole genome sequencing. We compared acquisition of single-nucleotide polymorphisms (SNPs), TB drug resistance mutations, and type of recurrence (endogenous reactivation [<8 SNPs] or exogenous reinfection [≥8 SNPs]) by DM status. Results Of 1633 enrolled in the 3 parent cohorts, 236 (14.5%) had microbiologically confirmed TB treatment failure/recurrence; 76 Mtb isolate pairs were available for sequencing (22 in TB-DM and 54 in TB-only). The SNP acquisition rate was overall was 0.43 (95% confidence interval [CI], .25–.64) per 1 person-year (PY); 0.77 (95% CI, .40–1.35) per 1 PY, and 0.44 (95% CI, .19–.86) per 1 PY at treatment failure and recurrence, respectively. Significant difference in SNP rates by DM status was seen at recurrence (0.21 [95% CI, .04–.61]) per 1 PY for TB-only vs 1.28 (95% CI, .41–2.98) per 1 PY for TB-DM; P = .02). No significant difference in SNP rates by DM status was observed at treatment failure. Acquired TB drug resistance was seen in 4 of 18 (22%) in TB-DM vs 4 of 45 (9%) in TB-only (P = .21). Thirteen (17%) participants had exogenous reinfection; the reinfection rate at recurrence was 25% (3/12) for TB-DM vs 17% (4/24) in TB-only (P = .66). Conclusions Considerable intrahost Mtb mutation rates were present at recurrence among patients with DM in India. One-fourth of patients with DM had exogenous reinfection at recurrence.

中文翻译：

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全基因组测序评估糖尿病对印度结核病突变和复发类型的影响

背景 描述糖尿病（DM）对结核分枝杆菌（Mtb）复发和突变率影响的证据有限。方法 本研究嵌套在印度患有和不患有糖尿病的结核病 (TB) 患者的 3 项队列研究中。配对的结核分枝杆菌分离株在基线时恢复，治疗失败/复发则进行全基因组测序。我们根据 DM 状态比较了单核苷酸多态性 (SNP)、结核病耐药突变和复发类型（内源性再激活 [<8 个 SNP] 或外源性再感染 [≥8 个 SNP]）。结果 在 3 个家长队列中登记的 1633 人中，236 人（14.5%）经微生物学证实结核病治疗失败/复发；76 个 Mtb 分离对可用于测序（22 个在 TB-DM 中，54 个在 TB-only 中）。SNP 获取率总体为每 1 人年 (PY) 0.43（95% 置信区间 [CI]，0.25-0.64）；治疗失败和复发时，每 1 PY 为 0.77 (95% CI, 0.40–1.35)，每 1 PY 为 0.44 (95% CI, 0.19–.86)。DM 状态的 SNP 率在复发时存在显着差异 (0.21 [95% CI, .04–.61])，仅 TB 的每 1 PY 与 TB 的每 1 PY 1.28 (95% CI, 0.41–2.98) -DM；P = .02)。治疗失败时，未观察到不同 DM 状态的 SNP 率存在显着差异。TB-DM 患者中 18 人中有 4 人 (22%) 出现获得性结核耐药性，而单纯 TB 患者中 45 人中有 4 人 (9%) (P = 0.21)。十三名（17%）参与者出现外源性再感染；TB-DM 患者复发时的再感染率为 25% (3/12)，而单纯 TB 患者的再感染率为 17% (4/24) (P = .66)。结论 印度 DM 患者复发时存在相当高的宿主内 Mtb 突变率。四分之一的糖尿病患者在复发时有外源性再感染。