Infectious Disease

The study shows that some household contacts are resistant to TB infection

April 08, 2021

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Baliashvili and Shah do not report any relevant financial information. In the study you will find all relevant financial information from all other authors.


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A study conducted in eight countries with moderate or high levels 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 contact studies with TB households and from public health work that some contacts remain negative when tested for TB infection even after prolonged exposure.” davit Baliashvili, a PhD student at the Rollins School of Public Health at Emory University, and N. Sarita Shah, MD, an associate professor there, said Healio.

Mycobacterium TB infographic

Source: Baliashvili D, et al. Clin Infect Dis. 2021; doi: 10.1093 / cid / ciab269.

“This fascinating observation raised the question of whether some people might be able to resist infection with Mycobacterium tuberculosis (Mtb) or get rid of an infection quickly,” they said. “If we can learn more about who these people are and what immunological or genetic factors enable them to resist infection, we can develop better biomedical prevention and treatment tools, including a TB vaccine.”

Baliashvili and Shah said the main challenges in this research area are to define who is resistant based on the currently “incomplete” TB testing and exposure measurements.

davit Baliashvili

“We had a unique opportunity to study a diverse population of household contacts with drug-resistant TB index cases in 16 locations in eight high and moderate TB exposure countries, where testing for TB infection and interviews were conducted on exposure to the index were. ” They said.

Baliashvili, Shah, and colleagues conducted a longitudinal study of index patients undergoing treatment for pulmonary multidrug- or rifampin-resistant TB, as well as 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 an interferon gamma release test (IGRA) at baseline and after 1 year. They quantified the exposure based on the infectiousness of the index patients, the interaction between index patients and household contact, and age. In addition, the researchers examined several definitions of resistance to TB infection by varying the TST negativity limit values ​​(0 vs. <5 mm), classification of missing test results and exposure level.

They rated a total of 1,016 contacts from 284 households. Five hundred and seventy-two contacts ages 5 and up had TST and longitudinal IGRA results available. A total of 77 (13%) or 71 (12%) contacts were classified as resistances with a TST threshold of less than 5 mm and 0 mm, respectively. Among 263 highly exposed contacts, 29 (11%) or 26 (10%) were classified as resistances using the limit values.

According to the researchers, this means that between 10% and 21% of household contacts are resistant to Mtb, despite being exposed to an infectious index in all of the definitions used in the study. They said that the prevalence of resistance did not differ significantly according to gender, age, HIV co-infection, or comorbid conditions.

“Although we have long known about individuals who are not infected with Mtb despite exposure, we have been hampered from further study of this important population due to limitations in defining a ‘resist phenotype’. Our study was able to examine different definitions using different tests for TB infection, exposure measures and follow-up, ”say Baliashvili and Shah. “Regardless of which definition we used, we have found that every tenth or up to every fifth contact can be classified as infection-resistant. By developing a common definition, research in this population can be conducted with a more unified approach to unlock potential clues to effectively prevent TB infection. ”


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David L. Cohn, MD)

David L. Cohn, MD

In contact examinations for tuberculosis, household contacts (HHCs) are the group most likely to be infected by people with active tuberculosis (index patents) and have priority for preventive therapy. A significant proportion may not be infected due to negative TSTs or IGRAs, which raises questions such as: Are HHCs really not infected when others in the same house are infected, and if not, are they somehow resistant to infection (“resistors”)?

Baliashvili and colleagues assessed the proportion of HHC who were likely to be resistant despite prolonged exposure to index patients with MDR-TB. This was a large, multinational, longitudinal study of HHC that was evaluated for its suitability for a clinical trial on the safety and efficacy of delamanid vs. isoniazid as a preventive therapy. Different definitions of resistance among HHC were examined based on limit values ​​for TSTs or IGRAs and exposure levels. Using the strictest definition (0 mm TST at baseline and negative IGRA at 1 year) in high exposure patients (index patients with AFB smear, cavitary disease, and household proximity), they estimated that at least 10% of the HHC were resistances.

The study’s strengths were a large sample size; Heterogeneity with several participating countries; and prevalence of the resister phenotype in line with previous studies in India and Uganda. Limitations included the accuracy and possible discordance of TSTs and IGRAs, as well as missing data for many participants. Multivariate analysis revealed no clinical or behavioral risk factors associated with the resist phenotype. The authors concluded that resistance to Mtb infection is likely due to genetic and immunological factors and that these mechanisms require further investigation, which may have implications for new treatments and vaccines.

David L. Cohn, MD

Infectious Disease News Editorial Board Member

Doctor, Denver Public Health

Professor of Medicine, Department of Infectious Diseases

University of Colorado Medical School

Disclosure: Cohn does not report any relevant financial information.


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