RESUMO
BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk. METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D < 50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies. CONCLUSION: Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.
Assuntos
Tuberculose/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Peru/epidemiologia , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Tuberculose/diagnóstico , Tuberculose/microbiologia , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Adulto JovemRESUMO
OBJECTIVES: To determine the prevalence of anemia (serum hemoglobin <10 g/dL) and assess zidovudine use and toxicity in HIV-positive pregnant women in India. METHODS: From 2002 through 2006, 24,105 pregnant women in Pune were screened for HIV and anemia. As part of an infant prevention of mother-to-child transmission (PMTCT) trial, enrolled HIV-positive women (n = 467) were assessed for anemia and associated outcomes, comparing women receiving zidovudine for >or=2 weeks versus no zidovudine. RESULTS: The prevalence of anemia was 38.7% in HIV-positive women. Anemic women were as likely as nonanemic women to receive zidovudine. At delivery, regardless of anemia status at enrollment, women receiving >or=2 weeks of zidovudine were 70% less likely to be anemic compared with women receiving no zidovudine (odds ratio = 0.28, 95% confidence interval: 0.14 to 0.57; P < 0.01), received iron and folic acid supplements for longer periods, and had no increased adverse delivery or newborn birth outcomes. CONCLUSIONS: A significant proportion of HIV-positive pregnant women in India present for antenatal care with anemia. With concurrent iron and folic acid supplementation, however, zidovudine use is not associated with persistent or worsening anemia or associated adverse outcomes. In Indian community settings, all pregnant HIV-positive women should receive early anemia treatment. Mild anemia should not limit zidovudine use for PMTCT in India.