Tuberculosis Infection Risk Varies by Age, Sex.

Almost twice as many men than women are diagnosed with tuberculosis globally, but little is known about the impact of a person’s sex on getting the disease. Previous research has suggested the gap in prevalence begins around puberty, with researchers hypothesizing that boys experience more exposure to tuberculosis-causing bacteria outside of the home as they grow up.

Now, a new study co-authored by School of Public Health and School of Medicine researchers finds boys and girls exposed to the disease at home are more likely to be infected with Mycobacterium tuberculosis at different ages, raising the possibility that hormonal differences play a role.

The study, published in Epidemiology and Infection, is one of the first to look directly at the interaction between age and sex on tuberculosis infection when someone else in the household has tuberculosis disease. The researchers found female members of a household have increased odds of infection when they are 5-14 years old, while males have increased odds at 15-39 years old.

“Studies are needed to explore why these differences were seen, but it may relate to differences in hormonal factors that affect susceptibility,” says senior author, Natasha Hochberg, assistant professor of medicine and epidemiology. “It’s also possible that girls and boys are exposed differently to the individual with tuberculosis disease, because of societal factors. As we move toward the WHO’s End TB goals, we need to consider all factors that affect the immune response to TB, and sex-based differences may be something we need to consider in greater depth.”

The researchers used data from a study of 917 household contacts of 160 tuberculosis patients in Vitória, Brazil, between 2008 and 2013. For the new study, the researchers focused on households where a first-time tuberculosis patient had at least three contacts who had never had tuberculosis previously. Household contacts were anyone who slept under the same roof or shared meals with the patient at least five days out of the week, watched television with them on nights and weekends, or visited the household at least 18 days out of each month. The researchers also noted whether contacts had been vaccinated against tuberculosis, and their sleeping proximity, contact hours, whether the contact was the patient’s caregiver, the number of meals shared, and whether the patient and contact were spouses, a parent and child, or had another kind of relationship.

They found 66.4 percent of household contacts were infected with tuberculosis, compared with an estimated community prevalence of 33 percent in Vitória. Among the household contacts, the prevalence of infection increased with age. Controlling for all of the collected variables, the researchers found the increase in infection was significant at a younger age in female contacts than male contacts, with the greatest increases for girls at 5–14 years old and for boys and men at 15–39 years old. Girls aged 5–14 also had an overall higher probability of infection than boys of the same age. Sex differences in tuberculosis infection prevalence disappeared by age 40.

The authors wrote that the higher risk for younger girls may be related to previous research that has found estrogen is protective against tuberculosis infection in experimental conditions. Future research should more specifically look at tuberculosis infection prevalence in girls before and after they begin menstruating, the authors wrote.

As for the higher rates of infection among boys and men ages 15-39, the authors note that exposure outside of the household may play a role.

The other SPH co-authors of the study were: Laura White, associate professor of biostatistics; Yicheng Ma, doctoral student in biostatistics; and alumni Theodore Tsacogianis (SPH’15) and Astrid Loomans (SPH’16), who were students while working on the study. The other MED and Boston Medical Center co-authors were Mary Gaeddert (SPH’11), Edward C. Jones-López, and Jerrold J. Ellner.

Priyanka Fernandes of Boston Children’s Hospital was lead author of the study. The other co-authors were Patricia Marques-Rodrigues, Geisa Fregona, and Reynaldo Dietze of the Universidade Federal do Espírito Santo in Vitória, Brazil.

—Michelle Samuels