Dr Carlton A Evans

Carlton A Evans,^1,3,5,9 Rosario Montoya,^3,9 Carlos Santillan,^3,9 Luz Caviedes,^3,9 Patricia Fuentes,^3,9 Giselle Soto,⁹ Vivian Kawai,⁹ Jessica Franco,^3,9 Teresa Valencia,^3,9 Jose Delgado,⁹ Mayuko Saito,^5,9 Lilia Cabrera,⁹ Rosa Pacheco,⁸ Edwin Garcia,² Inna Leybell,^3,5,9 Alejandro Necochea,^3,9 Mathew Baldwin,^3,9 Tom F. Pelly,^4,9 V Bhargavi Rao,^1,3,9 Oliver Boney,^4,9 Eunice Santiago,^3,9 Sarah Eisen,^3,9 Louise Pealing,^3,9 Robert E. Black,⁵ Siouxsie Wiles,¹ Douglas Young,¹ Barbara E. Golden,⁶ Tom Doherty,⁷ Carlos Vidal,² Eduardo Ticona,² Robert H. Gilman,^1,3,5,9 Jon S. Friedland,^1,5
1The Wellcome Centre for Clinical Tropical Medicine, Imperial College London; ²National TB control program, Ministry of Health, Peru; ³Dept Microbiology, Universidad Cayetano Heredia, Peru; ⁴University College London; ⁵Johns Hopkins Bloomberg School of Public Health, USA; ⁶University of Aberdeen, UK; ⁷London School of Hygiene & Tropical Medicine, UK; ⁸Universidad San Antonio Abad, Peru; ⁹Asociacion Benefica PRISMA, Peru.

 

We are investigating the determinants of TB susceptibility in Peru, focusing on the effects of malnutrition.

Peru has a high TB incidence and we have demonstrated widespread micronutrient deficiency that is significantly more frequent in TB patients.  In groups of patients, their household contacts and in healthy volunteers we have found an association between malnutrition and cutaneous anergy in TB skin test reactions.  We also found that topical micronutrient supplementation with zinc cream augmented delayed type hypersensitivity reactions, especially in people with low plasma zinc concentrations.  We have confirmed these results with oral micronutrient supplementation that also augmented tuberculin skin test responses.

To further investigate the effect of micronutrients on TB immunity, we have modified and validated an in vitro whole blood assay of antimycobacterial immunity for field use in developing countries.  Consistent with the tuberculin skin testing results, this whole blood assay has also demonstrated impaired antimycobacterial immunity in people with anthropometric evidence of malnutrition.  Research is in progress to establish whether micronutrient supplementation in vitro and in vivo reverses the immunosuppression associated with malnutrition.

Our results implicate micronutrient deficiency in TB susceptibility and we are therefore testing the hypothesis that micronutrient supplementation protects against TB disease.  To date, 800 participants have been recruited to an ongoing randomised, blinded, placebo-controlled trial of zinc, vitamin A and D supplementation in household contacts of recently diagnosed TB patients.  This study will demonstrate whether nutritional augmentation of antimycobacterial immunity is sufficient to reduce the risk of TB disease.

Dr Carlton A Evans is a Research Career Development Fellow in Clinical Tropical Medicine at the Wellcome Centre for Clinical Tropical Medicine in the Department of Infectious Diseases.