Drug-Resistant Tuberculosis Is Often Similar Among Household Members

Household members of patients with drug-resistant tuberculosis often have resistant infections, but differences with respect to specific drugs are common.

The resistance profiles of patients with drug-resistant tuberculosis may be useful in developing treatment plans for household contacts, according to a new study that examined the concordance of drug resistance profiles among household members.

For the study, published in Clinical Infectious Diseases, investigators performed a meta-analysis of 33 studies involving 484 secondary tuberculosis (TB) cases and their index cases in 17 countries between 1959 and 2016.

“We found that when household members of patients with drug-resistant TB are themselves diagnosed with TB, they usually also have drug-resistant TB,” Courtney M. Yuen, PhD, assistant professor at Harvard Medical School told Contagion®. “However, analyzing the full TB drug resistance profiles from patients who live in the same household often reveals differences with respect to some of the secondary drugs.”

Resistance profile concordance between index patients and household members was 54.3% overall. Patterns of susceptibility to isoniazid and rifampin had concordance of 82.6%. Genotypic concordance was at least as high, the study found.

For the subgroup analysis, the investigators looked at countries with a TB incidence of >100 per 100,000 in 2017, cases where members of the same household were diagnosed at the same time, and children under age 15 to determine whether those factors would affect concordance.

“I think one of the surprises was the high level of drug resistance among household members of drug-resistant TB patients in countries that have a lot of TB,” Yuen said. “Many people argue that in countries with a lot of TB, two people who live in the same home and who both get TB may not actually have the same type of TB, since they could easily have been infected separately, outside the home. However, we found that in studies published from these countries, when household members of patients with drug-resistant TB were themselves diagnosed with TB, almost 90% of them ended up having drug-resistant TB as well.”

Isoniazid/rifampin concordance was 88.6% for those countries—India, Kenya, Micronesia, Pakistan, Peru, Philippines, South Africa, and Vietnam—and resistance profile concordance was 46.1%.

The resistance profiles of TB patients could be useful in selecting TB preventive therapy for household contacts. Drug-susceptible regimens may often be inadequate and could contribute to more amplified resistance.

“If household members of a patient with drug-resistant TB is diagnosed with TB disease or infection, clinical management should assume drug resistance,” Yuen stated. “But drug resistance testing for household members with TB disease is still important.”

The study pointed to several possible factors contributing to higher discordance in the overall drug resistance profile, including: 1) lower reliability for drug susceptibility testing for various drugs, including pyrazinamide, ethambutol, and streptomycin; 2) the greater number of drugs being tested increases the chances of false discordance; and 3) index patients may have transmitted the disease before resistance was acquired.

“I think that there needs to be investment in helping countries with large TB burdens build capacity for drug resistance testing,” Yuen said. “When treating TB, it is important not just to know whether it is drug-resistant, but exactly what drugs it is resistant to. We found that even when TB patients living in the same home both had drug-resistant TB, the exact drug resistance profile was often different. Building laboratory capacity for rapid drug resistance testing is therefore important to make sure that these patients get the right treatment.”

TB is the leading cause of death from infectious disease worldwide, causing about 1.3 million deaths per year, mostly in the developing world. The respiratory virus M tuberculosis is spread via airborne transmission and more often affects men, who account for 60% of all cases, according to a recent study.

Recent estimates suggest 70% or more of childhood TB infections come from outside of the home. The US Food and Drug Administration recently approved a pediatric formulation of bedaquiline for the treatment of multi-drug resistant TB in children age 5 and older.