Standard TB tests may not detect infection in certain exposed individuals
CLEVELAND – An international collaboration of infectious disease experts has identified a large group of people who appear to have naturally mounted an immune response to TB, a bacterial infection that is the leading cause of infectious disease death worldwide. Nearly 200 people from 2500 households with active TB were clearly exposed to TB for more than 10 years but the two most reliable tests (TST and IGRA) came back negative on repeated tests.
“Further research is needed, but it seems that either the
tests are not sufficiently sensitive to detect a low-level case
of TB or some people are mounting a natural defense, which is
what we believe is happening,” said W. Henry Boom, MD,
Division Chief of Infectious Disease and HIV Medicine at
University Hospitals (UH) Cleveland Medical Center and Case
Western Reserve University (CWRU) School of Medicine.
Boom was a co-author of the research published May 20 in Nature
Medicine. He was joined in that research by Catherine M. Stein,
PhD, of the Department of Population & Quantitative Health
Sciences at CWRU School of Medicine. The study also included
colleagues from the Uganda-CWRU Research Collaboration clinic,
Makerere University in Uganda, the University of Washington, the
Ragon Institute of Massachusetts General Hospital, Massachusetts
Institute of Technology, and Harvard University.
“TB remains the leading infectious cause of death
worldwide, and for that reason, these findings about natural
defenses by a significant sample – eight percent –
of people exposed to TB over more than 10 years is
eye-opening,” said Dr. Boom. “This may point us to a
signature among people who appear to be naturally immune that
could inform vaccine development.” said Dr. Boom.
“It also is possible that we need to reconsider the
standard TB tests to take into consideration for very low level
cases of TB,” he continued. “Clearly, we need to
investigate further, as the imperative to find prevention,
treatment and cure for TB is pressing.”
The study looked at more than 2500 households in Uganda that had
individuals with active TB. The researchers found 198
individuals (8.2 percent) who lived in these households for more
than 10 years but who never tested positive on the Tuberculin
Skin Test (TST, developed in 1886) or the more modern blood test
interferon-gamma release assay (IGRA). This meant they were
either “resistant” to the Mtb infection or not being
detected by the two standard tests.
“We found through molecular profiling of these individuals
that they had been exposed to the bacteria,” said Dr.
Boom. “They had likely been infected, but did not exhibit
signs or symptoms of Mtb infection and the tests were standard
tests were negative. We assume that they mounted a natural
immune response, but need to explore further.
The Uganda-CWRU Research Collaboration recently marked its
30th anniversary. Three UH physicians are the key
US-based principal investigators for this collaboration: Dr.
Boom, John Johnson, MD, and Robert Salata, MD, Chair of
Medicine, and on the faculty of CWRU School of Medicine. They
are joined in this collaboration by Catherine Stein, PhD with
CWRU School of Medicine, who has worked on the epidemiology of
TB in Uganda for most of her career.
Journal Reference:
- Lenette L. Lu, Malisa T. Smith, Krystle K. Q. Yu, Corinne Luedemann, Todd J. Suscovich, Patricia S. Grace, Adam Cain, Wen Han Yu, Tanya R. McKitrick, Douglas Lauffenburger, Richard D. Cummings, Harriet Mayanja-Kizza, Thomas R. Hawn, W. Henry Boom, Catherine M. Stein, Sarah M. Fortune, Chetan Seshadri, Galit Alter. IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure. Nature Medicine, 2019; 25 (6): 977 DOI: 10.1038/s41591-019-0441-3
