Wellcome Trust Major Overseas Programme, Hospital for Tropical Diseases, Oxford University Clinical Research Unit, 764 Vo Van Kiet Street, District 5, Ho Chi Minh City, Vietnam.
Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam.
BMC Infect Dis. 2018 Oct 1;18(1):494. doi: 10.1186/s12879-018-3383-3.
The depletion of CD4 cell is the underlying reason for TB hyper-susceptibility among people with HIV. Consequently, the trend of TB dynamics is usually hidden by the HIV outbreak.
Here, we aim to evaluate the trend of TB dynamics quantitatively by a simple mathematical model using the known prevalence of hyper-susceptible individuals in the population. In order to estimate the parameters governing transmission we fit this model in a maximum likelihood framework to both reported TB cases and data from samples tested with Interferon Gamma Assay from Ho Chi Minh City - a city with high TB transmission and strong synchronization between HIV/AIDS and TB dynamics.
Our results show that TB transmission in HCMC has been declining among people without HIV; we estimate a 18% (95% CI: 9-25%) decline in the transmission parameter between 1996 and 2015. Furthermore, we show that co-infected patients have limited contribution to the transmission process. For hyper-susceptible individuals, our model suggests that the risk of a new active TB infection occurring is significantly higher than the risk of relapsed active TB, while this is not the case for people without hyper-susceptibility.
The increase of TB notifications in Ho Chi Minh City from 1996 to 2008 is evitable when, as occurred, the number of hyper-susceptible individuals increased faster than the decrease of TB transmission rate. The sharp decrease in TB notifications observed in this city from 2008 to 2015 is the combined result of the decrease of TB transmission rate and the decrease of hyper-susceptible individuals in the population. For hyper-susceptible individuals, we propose that the reason for the reduced relapsed active TB risk is HIV treatment delay. According to HIV treatment guidelines issued by Vietnam's Ministry of Health, hyper-susceptible individuals usually have to wait until their CD4 cell count falls under 350 cells/μl to start ART. Once patients begin ART, they will remain on ART for the rest of their life and thus have greater protection against relapses of TB. We therefore hypothesize that the delay in using ART imposes considerable TB burden on HCMC despite the declining transmission process.
CD4 细胞耗竭是 HIV 感染者发生结核高度易感性的根本原因。因此，结核动态趋势通常被 HIV 疫情所掩盖。
在这里，我们旨在通过使用人群中已知的高度易感性个体的患病率，使用一个简单的数学模型来定量评估结核动态趋势。为了估计控制传播的参数，我们在最大似然框架中拟合该模型，同时拟合报告的结核病例数据和胡志明市进行干扰素γ测定的样本数据 - 一个结核传播率高且 HIV/AIDS 和结核动态同步性强的城市。
我们的结果表明，胡志明市无 HIV 人群的结核传播一直在下降；我们估计在 1996 年至 2015 年间，传播参数下降了 18%（95%CI：9-25%）。此外，我们还表明，合并感染患者对传播过程的贡献有限。对于高度易感性个体，我们的模型表明，新发活动性结核感染的风险明显高于复发性活动性结核的风险，而对于无高度易感性的个体则并非如此。
当胡志明市的高度易感性个体数量增加速度快于结核传播率下降速度时，就不可避免地会出现 1996 年至 2008 年结核报告病例的增加。从 2008 年至 2015 年，该市结核报告病例的急剧下降是结核传播率下降和人群中高度易感性个体数量减少的综合结果。对于高度易感性个体，我们提出 HIV 治疗延迟是复发性活动性结核风险降低的原因。根据越南卫生部发布的 HIV 治疗指南，高度易感性个体通常要等到 CD4 细胞计数降至 350 个/μl 以下才开始接受 ART。一旦患者开始接受 ART，他们将终生接受 ART，从而对结核病的复发有更大的保护作用。因此，我们假设尽管传播过程在下降，但 ART 的延迟使用仍给胡志明市带来了相当大的结核病负担。
