Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital, Blantyre, Malawi.
BMC Med. 2021 Nov 10;19(1):298. doi: 10.1186/s12916-021-02128-9.
Ratios of bacteriologically positive tuberculosis (TB) prevalence to notification rates are used to characterise typical durations of TB disease. However, this ignores the clinical spectrum of tuberculosis disease and potentially long infectious periods with minimal or no symptoms prior to care-seeking.
We developed novel statistical models to estimate progression from initial bacteriological positivity including smear conversion, symptom onset and initial care-seeking. Case-detection ratios, TB incidence, durations, and other parameters were estimated by fitting the model to tuberculosis prevalence survey and notification data (one subnational and 11 national datasets) within a Bayesian framework using Markov chain Monte Carlo methods.
Analysis across 11 national datasets found asymptomatic tuberculosis durations in the range 4-8 months for African countries; three countries in Asia (Cambodia, Lao PDR, and Philippines) showed longer durations of > 1 year. For the six countries with relevant data, care-seeking typically began half-way between symptom onset and notification. For Kenya and Blantyre, Malawi, individual-level data were available. The sex-specific durations of asymptomatic bacteriologically-positive tuberculosis were 9.0 months (95% credible interval [CrI]: 7.2-11.2) for men and 8.1 months (95% CrI: 6.2-10.3) for women in Kenya, and 4.9 months (95% CrI: 2.6-7.9) for men and 3.5 months (95% CrI: 1.3-6.2) for women in Blantyre. Age-stratified analysis of data for Kenya showed no strong age-dependence in durations. For Blantyre, HIV-stratified analysis estimated an asymptomatic duration of 1.3 months (95% CrI: 0.3-3.0) for HIV-positive people, shorter than the 8.5 months (95% CrI: 5.0-12.7) for HIV-negative people. Additionally, case-detection ratios were higher for people living with HIV than HIV-negative people (93% vs 71%).
Asymptomatic TB disease typically lasts around 6 months. We found no evidence of age-dependence, but much shorter durations among people living with HIV, and longer durations in some Asian settings. To eradicate TB transmission, greater gains may be achieved by proactively screening people without symptoms through active case finding interventions.
细菌学阳性结核病(TB)的患病率与报告率之比用于描述结核病的典型持续时间。然而,这忽略了结核病的临床谱,以及在寻求医疗护理之前可能存在的无症状或症状轻微但具有传染性的长期潜伏期。
我们开发了新的统计模型来估计从初始细菌学阳性到包括痰涂片转换、症状出现和首次寻求医疗护理的进展。通过在贝叶斯框架内使用马尔可夫链蒙特卡罗方法拟合模型,根据结核病患病率调查和报告数据(一个次国家级和 11 个国家级数据集)来估计病例检出率、TB 发病率、持续时间和其他参数。
对 11 个国家级数据集的分析发现,非洲国家的无症状结核病持续时间为 4-8 个月;亚洲的三个国家(柬埔寨、老挝人民民主共和国和菲律宾)显示持续时间超过 1 年。对于有相关数据的六个国家,寻求医疗护理通常在症状出现和报告之间的一半开始。对于肯尼亚和布兰太尔,马拉维,有个人层面的数据。肯尼亚和布兰太尔,男女之间的无症状细菌学阳性结核病的持续时间分别为男性 9.0 个月(95%可信区间[CrI]:7.2-11.2)和女性 8.1 个月(95% CrI:6.2-10.3);男性 4.9 个月(95% CrI:2.6-7.9)和女性 3.5 个月(95% CrI:1.3-6.2)。肯尼亚的年龄分层数据分析显示,持续时间没有明显的年龄依赖性。对于布兰太尔,HIV 分层分析估计 HIV 阳性人群的无症状持续时间为 1.3 个月(95% CrI:0.3-3.0),短于 HIV 阴性人群的 8.5 个月(95% CrI:5.0-12.7)。此外,HIV 阳性人群的病例检出率高于 HIV 阴性人群(93%对 71%)。
无症状 TB 疾病通常持续约 6 个月。我们没有发现年龄依赖性的证据,但 HIV 阳性人群的持续时间要短得多,而在一些亚洲地区的持续时间要长。为了消除 TB 传播,通过主动病例发现干预措施主动筛查无症状人群,可能会取得更大的成效。