Undernourished household members at increased risk for developing TB after exposure

(Boston)—Mycobacterium tuberculosis, the bacteria that causes tuberculosis (TB), is distinct from most germs in its capacity to silently infect individuals for months and even years before waking up and causing active disease that can lead to severe illness and death. The immune system plays an important role in controlling the germ and keeping it dormant.

Decades of epidemiological data have linked undernutrition to TB. While undernourished individuals have blunted immune systems, a phenomenon which has been dubbed nutritionally acquired immune deficiency (N-AIDS), it is not clear why undernourished individuals are at increased risk of TB disease.

In a new study that followed household contacts (family members/people who share the same dwelling) of persons with TB, researchers have found that undernourished household contacts were three times more likely to progress to TB disease.  The study did not find that undernourished contacts were at increased risk of testing positive for TB infection as compared to well-nourished individuals.

“Are they more likely to become infected with the TB germ? Or are their immune systems unable to contain the germ resulting in severe disease? This fundamental question is important to answer as it can guide how we can best protect undernourished individuals who form a key and vulnerable population in the fight against TB,” explained corresponding author Pranay Sinha, MD, assistant professor of medicine at Boston University Chobanian & Avedisian School of Medicine.

The researchers, which included investigators from both U.S. and Indian institutions (which are part of the Regional Prospective Observational Research for Tuberculosis (RePORT) India consortium), identified nearly 900 household contacts of persons who were newly diagnosed with TB, screening them to make sure they did not have TB disease at enrollment. They then followed these contacts to see if they developed TB disease for up to four years. Those who had a negative TB infection test at enrollment were retested to see if it had turned positive. The researchers then compared the rate of TB disease and TB infection between undernourished household contacts and well-nourished household contacts.

According to the researchers, these findings have clinical implications. “We now have greater insight into the mechanism by which undernutrition leads to greater TB risk. It is not by increasing infection, instead, it is by failing to contain the infection when it happens. Fortunately, undernutrition is a modifiable risk factor. Our findings should prompt TB programs to promptly provide adequate rations for the entire household to prevent TB disease among household contacts in addition to TB preventive therapy,” adds Sinha.

These findings appear online in the journal Clinical Infectious Diseases.

This project was funded in whole or in part with federal funds from the government of India’s DBT, the ICMR, the NIH, National Institute of Allergy and Infectious Diseases (NIAID), Office of AIDS Research and distributed in part by CRDF Global. In addition, the following funding sources have supported this work: P. S. is supported by NIAID (award K01AI167733-01A1) as well as funds distributed via CRDF Global (award DAA3-19-65673-1), the Warren Alpert Foundation (6005415), the Burrough’s Wellcome Fund/American Society of Tropical Medicine and Hygiene fellowship, and a career investment award from the Department of Medicine at Boston University Chobanian & Avedisian School of Medicine;  A. G., N. G., V. M., M.P.  and A. N. G. are supported by NIAID via CRDF Global (awards DAA3-19-65671-1 and DAA3-18-64774-1) and by NIAID (award R01A1I097494); A. N. G. is supported by NIAID (award K99AI151094); and V. V. and H. K. are supported by the Indian DBT (grant USB1-31149-XX-13). A. G. also reports support for this work in the form of funding paid to institution from NIH, Unitaid, and the Centers for Disease Control and Prevention, outside the submitted work. S. G. and V. M. report support for this work in the form of NIH funding for Johns Hopkins Baltimore–Washington–India Clinical Trials Unit from NIAID Networks and CRDF Global, payment to institution.