Micronutrient supplementation augments anti-mycobacterial immune responses in tst reactive household contacts



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Micronutrient supplementation augments anti-mycobacterial immune responses in TST reactive household contacts
Saunders MJ1,2,3, Zevallos K1,2, Tovar MA1,2,, Montoya R1, Santillan C1,2, Baldwin M1,2, Schumacher S1,2, Evans CA1,2,3
Author affiliations:

  1. Innovación Por la Salud Y Desarrollo (IPSYD), Asociación Benéfica PRISMA, Lima, Perú

  2. Innovation For Health And Development (IFHAD), Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Perú

  3. Infectious Diseases & Immunity, Imperial College London, and Wellcome Trust Imperial College Centre for Global Health Research, London, UK


Background. The tuberculin-skin-test (TST) is used to diagnose tuberculosis infection and guide preventive therapy prescription in household contacts of patients with tuberculosis. Sensitivity is limited by reduced reactivity in undernourished people at highest risk of developing disease. Micronutrient deficiencies are implicated in reduced TST reactivity as they are important determinants of anti-mycobacterial immunity. We previously demonstrated that topical zinc cream applied to TST augmented immune response sufficiently to improve diagnosis of tuberculosis infection. Because topical zinc is inconvenient, we investigated whether oral micronutrient supplementation augments TST indurations and improves diagnosis.
Methods. Between 2002-2006 we recruited 867 household contacts aged ≥15 years of 334 index cases with laboratory confirmed pulmonary tuberculosis. Each contact received one intradermal injection with tuberculin (0.5 IU in 0.1ml). Trained nurses read the resulting indurations after 48hrs. Participants were randomised to immediately receive either one dose of micronutrients (combined vitamin D 400 IU, vitamin A 5000 IU and zinc 25mg) or placebo. Indurations were re-read by nurses at 72hrs and the difference between the 72hr and 48hr indurations calculated.
Results. The median induration at 48hrs was 11mm. There was no difference in 48-72hr augmentation between the micronutrient and placebo groups (mean increase=0.68 vs 0.62; p=0.6). Among participants with an induration >10mm at 48hrs, micronutrient supplementation significantly augmented TST results at 72hrs compared to placebo (mean increase=0.71 versus 0.34, p=0.05). Using a threshold of ≥15mm to diagnose TB infection, micronutrient supplementation significantly increased the odds of converting from a negative result at 48hrs to a positive result at 72hrs compared to placebo (odds ratio=2.2, 95%CI:1.2-4.0; p=0.01) (Figure).
Conclusion. In TST reactive individuals, one dose of micronutrient supplementation taken 48hrs after the initial tuberculin injection significantly augmented anti-mycobacterial immune responses and thus may improve sensitivity of TST in undernourished household contacts.


Figure: Proportion of contacts who converted from a negative TST result at 48hrs to a positive TST result at 72hrs according to allocation



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