Mycobacteria Research Laboratories, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, USA.
Department of Internal Medicine, McGovern Medical School, Houston, Texas, USA.
Clin Infect Dis. 2022 Dec 19;75(12):2178-2185. doi: 10.1093/cid/ciac326.
Although previous studies have shown that vitamin A deficiency is associated with incident tuberculosis (TB) disease, the direction of the association has not been established. We investigated the impact of vitamin A deficiency on TB disease progression.
We conducted a longitudinal cohort study nested within a randomized clinical trial among HIV-infected patients in Haiti. We compared serial vitamin A levels in individuals who developed TB disease to controls matched on age, gender, follow-up time, and time to antiretroviral therapy initiation. We also evaluated histopathology, bacterial load, and immune outcomes in TB infection in a guinea pig model of dietary vitamin A deficiency.
Among 773 participants, 96 developed incident TB during follow-up, 62.5% (60) of whom had stored serum samples obtained 90-365 days before TB diagnosis. In age- and sex- adjusted and multivariate analyses, respectively, incident TB cases were 3.99 times (95% confidence interval [CI], 2.41 to 6.60) and 3.59 times (95% CI, 2.05 to 6.29) more likely to have been vitamin A deficient than matched controls. Vitamin A-deficient guinea pigs manifested more extensive pulmonary pathology, atypical granuloma morphology, and increased bacterial growth after experimental TB infection. Reintroduction of dietary vitamin A to deficient guinea pigs after established TB disease successfully abrogated severe disease manifestations and altered cellular immune profiles.
Human and animal studies support the role of baseline vitamin A deficiency as a determinant of future TB disease progression.
尽管先前的研究表明维生素 A 缺乏与结核病（TB）发病有关，但尚未确定两者之间的关联方向。我们调查了维生素 A 缺乏对结核病进展的影响。
我们在海地进行了一项 HIV 感染患者的纵向队列研究，其中嵌套了一项随机临床试验。我们比较了发展为结核病的个体和年龄、性别、随访时间和开始抗逆转录病毒治疗时间相匹配的对照者的连续维生素 A 水平。我们还在维生素 A 缺乏的豚鼠模型中评估了结核病感染的组织病理学、细菌负荷和免疫结果。
在 773 名参与者中，有 96 名在随访期间发生了结核病发病，其中 62.5%（60 名）在结核病诊断前 90-365 天获得了储存的血清样本。在年龄和性别调整的以及多变量分析中，分别有 3.99 倍（95%置信区间 [CI]，2.41 至 6.60）和 3.59 倍（95% CI，2.05 至 6.29）的结核病发病病例更有可能发生维生素 A 缺乏比匹配对照者。缺乏维生素 A 的豚鼠在实验性结核病感染后表现出更广泛的肺部病理学、非典型肉芽肿形态和细菌生长增加。在确诊结核病后，向缺乏维生素 A 的豚鼠重新引入饮食中的维生素 A 成功地消除了严重的疾病表现并改变了细胞免疫谱。
人类和动物研究支持基线维生素 A 缺乏作为未来结核病进展的决定因素的作用。
