Facts & figures
Leading large clinical trials in Vietnam, Associate Professor Greg Fox is addressing the problem of tuberculosis (TB) case detection in endemic settings using active screening and a modern new molecular test.
Affecting 10.4 million people each year, TB is the leading infectious cause of death worldwide. In 2017, almost two million people died from this illness, most in low and middle-income countries.
TB is a treatable respiratory disease and, if detected early, can usually be completely cured with antibiotics. Despite this, morbidity and mortality rates remain high because of under-diagnosis. According to the World Health Organization, one third of people with TB are never diagnosed.
To tackle this case detection gap, Associate Professor Greg Fox has been evaluating the effectiveness of active screening in Vietnam. His work aligns with the WHO End TB Strategy, which aims to eliminate TB by the middle of the century and reduce TB deaths by 95 percent before 2035.
More than 35,000 people across Vietnam participated in ACT2, the initial randomised controlled trial conducted by Associate Professor Fox and his team. Their findings have the potential to transform global TB control efforts.
A key driver of the high mortality and continuing transmission of TB is the substantial gap between the number of people with the disease and the number who are detected
“Our research tested the effect of new active screening strategies on TB detection and risk of death. In the two years after participation in our study, the number of cases that were detected more than doubled in the active screening intervention group. The study also showed that screening for TB reduced the risk of death.”
The second trial, led by Professor Guy Marks and Associate Professor Fox (ACT3), evaluated the effectiveness of a new molecular diagnostic test called GeneXpert in diagnosing TB, requiring sputum specimen from 23,000 people.
“We found that the GeneXpert test was substantially more accurate than previously recognised,” says Associate Professor Fox. “The specificity of GeneXpert was at least 99.78%, with a positive predictive value of at least 61%.
“These findings show, for the first time, that molecular methods are highly accurate when used as screening assays for TB, and are suitable for community-wide screening. This novel approach may transform active case finding for TB in moderate risk populations.”
The two trials have had major implications for global TB reduction efforts. The results provide the evidence required to justify the expansion of programs to screen household contacts of TB patients to high-burden settings.
Associate Professor Fox developed an interest in international health through short placements in Malawi and Timor-Leste during his medical training. He later completed a Master of International Public Health degree at the University of Sydney before pursuing a research pathway.
His interest in research stems from a commitment to improving the health care of disadvantaged communities in low and middle-income countries.
He was awarded the University of Sydney Cornforth Medal for PhD achievement in 2013 after completing extensive research on TB which was later published in the New England Journal of Medicine.
In the years since the initial studies were completed, he has worked with collaborators from the Vietnam National TB Program to determine ways to increase case detection. This included the completion of ACT4, a six-country randomised controlled trial conducted in partnership with McGill University in Canada, which has provided evidence that will help countries to scale up screening and treatment for latent TB infection.
“Thanks to the commitment of our Vietnamese colleagues, contact investigation has been implemented routinely throughout the two provinces of Vietnam participating in the ACT4 study, and it will be implemented nationally over the coming years,” says Associate Professor Fox.