The Impact of Preventive Treatment for Multidrug- and Rifampin-Resistant Tuberculosis Exceeds Trial-Based Estimates.
The Impact of Preventive Treatment for Multidrug- and Rifampin-Resistant Tuberculosis Exceeds Trial-Based Estimates.
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预防性治疗对耐多药和利福平结核病的影响超出了基于试验的估计。
DOI：
10.1093/cid/ciad557
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Kendall,EmilyA
中科院分区：
文献类型：
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作者：
Kasaie,Parastu;Pennington,Jeff;Gupta,Amita;Dowdy,DavidW;Kendall,EmilyA
背景：针对耐多药或利福平结核病（MDR/RR-TB）患者家庭接触者进行结核病预防治疗（TPT）的几项临床试验即将完成。向MDR/RR-TB接触者提供TPT的潜在益处超出了临床试验可以衡量的结果。方法我们开发了一个基于代理的、家庭结构的结核病和耐多药/耐药结核病传播模型，并根据印度的说明性环境进行了校准。我们在MDR/RR-TB患者的家庭中模拟接触调查，比较MDR/RR-TPT方案（假设持续时间为6个月，有效率为70%）和相关的主动病例发现与不进行TPT或不进行家庭干预的接触调查替代方案。我们模拟了2年内相对于安慰剂避免的结核病和MDR/RR-TB发病率，通过一项典型试验来测量，以及在更长的时间范围内，在更广泛的人群中，相对于无接触调查避免的发病率。结果与一项典型试验一样，对TPT和安慰剂接受者进行了为期2年的观察，测量了MDR/RR-TPT在接受者中预防了72%（四分位数范围为45%-100%）的MDR/RR-TB事件；与安慰剂相比，预防1例MDR/RR-TB病例所需治疗（NNT）的中位数为73。在13-18年的观察中，这一NNT下降到54，当还考虑下游传播影响时下降到27，当与无家庭接触干预情景相比，包括主动结核病筛查的影响时下降到12。如果即将到来的试验结果证明有效，TPT对MDR/RR-TB的长期人群影响-包括在MDR/RR-TB接触者中增加活动性结核病检出率的巨大影响-可能远远大于试验结果本身。
BackgroundSeveral clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug- or rifampin-resistant tuberculosis (MDR/RR-TB) are nearing completion. The potential benefits of delivering TPT to MDR/RR-TB contacts extend beyond the outcomes that clinical trials can measure.MethodsWe developed an agent-based, household-structured TB and MDR/RR-TB transmission model, calibrated to an illustrative setting in India. We simulated contact investigation in households of patients with MDR/RR-TB, comparing an MDR/RR-TPT regimen (assuming 6-month duration, 70% efficacy) and associated active case finding against alternatives of contact investigation without TPT or no household intervention. We simulated the TB and MDR/RR-TB incidence averted relative to placebo over 2 years, as measurable by a typical trial, as well as the incidence averted over a longer time horizon, in the broader population, and relative to no contact investigation.ResultsObserving TPT and placebo recipients for 2 years as in a typical trial, MDR/RR-TPT was measured to prevent 72% (interquartile range, 45%–100%) of incident MDR/RR-TB among recipients; the median number needed to treat (NNT) to prevent 1 MDR/RR-TB case was 73, compared to placebo. This NNT decreased to 54 with 13–18 years of observation, to 27 when downstream transmission effects were also considered, and to 12 when the effects of active TB screening were included by comparing to a no-household-contact-intervention scenario.ConclusionsIf forthcoming trial results demonstrate efficacy, the long-term population impact of TPT for MDR/RR-TB—including the large effect of increased active TB detection among MDR/RR-TB contacts—could be much greater than suggested by trial outcomes alone.