April 08, 2021
2 min read
Baliashvili and Shah report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
A study conducted in eight countries with a middle or high burden of tuberculosis found that at least 10% of household contacts can be classified as resistant to TB infection, including those with high exposure.
“We know from decades of TB household contact studies and public health work that some contacts remain negative on tests for TB infection, even after prolonged exposure,” Davit Baliashvili, a PhD student at the Emory University Rollins School of Public Health, and N. Sarita Shah, MD, an associate professor there, told Healio.
“This intriguing observation raised the question of whether some individuals may be able to resist becoming infected with Mycobacterium tuberculosis (Mtb) or can rapidly clear an infection,” they said. “If we can learn more about who these individuals are and what immunologic or genetic factors allow them to resist infection, we can develop better biomedical prevention and treatment tools, including a TB vaccine.”
Baliashvili and Shah said key challenges in this area of research include defining who is resistant based on the currently “imperfect” tests for TB and measurements of exposure.
“We had a unique opportunity to examine a diverse population of household contacts of drug-resistant TB index cases from 16 sites in eight high- and medium-TB burden countries who had undergone testing for TB infection and interviews about exposure to the index case,” they said.
Baliashvili, Shah and colleagues conducted a longitudinal study of index patients enrolled in treatment for pulmonary multidrug- or rifampin-resistant TB and their household contacts in Botswana, Brazil, Haiti, India, Kenya, Peru, South Africa and Thailand.
According to the study, they tested contacts for TB infection with a tuberculin skin test (TST) and interferon-gamma release assay (IGRA) at baseline and after 1 year. They quantified exposure based on index patients’ infectiousness, index patient and household contact interaction, and age. Additionally, the researchers explored multiple definitions of resistance to TB infection by varying TST negativity cut-offs (0 vs. < 5 mm), classification of missing test results and exposure level.
In total, they evaluated 1,016 contacts from 284 households. Five hundred and seventy-two contacts aged 5 years and older had TST and longitudinal IGRA results available. Overall, 77 (13%) or 71 (12%) contacts were classified as resisters with a less than 5 mm or 0 mm TST threshold, respectively. Among 263 highly exposed contacts, 29 (11%) or 26 (10%) were classified as resisters using the cut-offs, respectively.
According to the researchers, this translated to between 10% and 21% of household contacts being resistant to Mtb despite substantial exposure to an infectious index case across all definitions used in the study. They said the prevalence of resisters did not differ substantially by sex, age, HIV coinfection or comorbid conditions.
“Even though we have long known about individuals who remain uninfected with Mtb despite exposure, we have been hampered in further studying this important population due to limitations in defining a ‘resister phenotype.’ Our study was able to examine several definitions using various tests for TB infection, exposure measures, and follow-up,” Baliashvili and Shah said. “Regardless of which definition we used, we found one in 10 — or up to one in five — contacts could be classified as resisting infection. Developing a common definition can allow research in this population to be conducted with a more uniform approach to unlock potential clues to effectively prevent TB infection.”