Trial reportPloS one2016
Low Vitamin-D Levels Combined with PKP3-SIGIRR-TMEM16J Host Variants Is Associated with Tuberculosis and Death in HIV-Infected and -Exposed Infants.
Trial report in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00080119 (A Randomized, Double Blind, Placebo Controlled Trial to Determine the Efficacy of Isoniazid), which is not on this map. Cited by 10 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Double Blind, Placebo Controlled Trial to Determine the Efficacy of Isoniazid (INH) in Preventing Tuberculosis Disease and Latent Tuberculosis Infection Among Infants With Perinatal Exposure to HIV
Who cites it
10 citing papers in PubMed, 3 syntheses or guidelines pooled it, 23 citations in OpenAlex.
- Association of variant vitamin statuses and tuberculosis development: a systematic review and meta-analysis.Annals of medicine · 2024Pooled it
- Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis.PLoS medicine · 2019Pooled it
- The association between vitamin D status and tuberculosis in children: A meta-analysis.Medicine · 2018Pooled it
- Predictors of TB disease in HIV-exposed children from Southern Africa.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2023Trial
- The scramblase anoctamin 9 controls the immune response in lymphocytes.Cellular and molecular life sciences : CMLS · 2026Article
- The role of vitamin D and the VDR gene polymorphism in sepsis risk and mortality: a systematic review and meta-analysis.Osong public health and research perspectives · 2025Article
- Exploring the value of Mycobacterium tuberculosis modified lipoprotein as a potential biomarker for TB detection in children.BMC infectious diseases · 2022Article
- Tuberculosis susceptibility and protection in children.The Lancet. Infectious diseases · 2019Review
- Malnutrition: Modulator of Immune Responses in Tuberculosis.Frontiers in immunology · 2017Review
- Vitamin D deficiency associates with susceptibility to tuberculosis in Pakistan, but polymorphisms in VDR, DBP and CYP2R1 do not.BMC pulmonary medicine · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 9 institutions in 2 countries.
Funding
Abstract
backgroundThis study examined the associations of 25-hydroxyvitamin D and specific host genetic variants that affect vitamin D levels or its effects on immune function, with the risk of TB or mortality in children.
methodsA case-cohort sample of 466 South African infants enrolled in P1041 trial (NCT00080119) underwent 25-hydroxyvitamin D testing by chemiluminescent immunoassay. Single nucleotide polymorphisms (SNPs) that alter the effect of vitamin D [e.g. vitamin D receptor (VDR)], vitamin D levels [e.g. vitamin D binding protein (VDBP)], or toll like receptor (TLR) expression (SIGIRR including adjacent genes PKP3 and TMEM16J) were identified by real-time PCR. Outcomes were time to TB, and to the composite of TB or death by 192 weeks of follow-up. Effect modification between vitamin D status and SNPs for outcomes was assessed.
findingsMedian age at 25-hydroxyvitamin D determination was 8 months; 11% were breastfed, 51% were HIV-infected and 26% had low 25-hydroxyvitamin D (<32ng/mL). By 192 weeks, 138 incident TB cases (43 definite/probable, and 95 possible) and 26 deaths occurred. Adjusting for HIV status and potential confounders, low 25-hydroxyvitamin D was associated with any TB (adjusted hazard ratio [aHR] 1.76, 95% CI 1.01-3.05; p = 0.046) and any TB or death (aHR 1.76, 95% CI 1.03-3.00; p = 0.038). Children with low 25-hydroxyvitamin D and TMEM 16J rs7111432-AA or PKP3 rs10902158-GG were at increased risk for probable/definite TB or death (aHR 8.12 and 4.83, p<0.05) and any TB or death (aHR 4.78 and 3.26, p<0.005) respectively; SNPs in VDBP, VDR, and vitamin D precursor or hydroxylation genes were not. There was significant interaction between low 25-hydroxyvitamin D and, TMEM 16J rs7111432-AA (p = 0.04) and PKP3 rs10902158-GG (p = 0.02) SNPs.
conclusionsTwo novel SNPs, thought to be associated with innate immunity, in combination with low vitamin D levels were identified as increasing a young child's risk of developing TB disease or death. Identifying high-risk children and providing targeted interventions such as vitamin D supplementation may be beneficial.
trial registrationClinicalTrials.gov NCT00080119.
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