Adding household screening to standard passive case finding more than doubled the detection of tuberculosis cases during a nearly 5-year study in Vietnam, where the disease is prevalent but undertreated, according to findings published today in The New England Journal of Medicine.
“These findings are critical,” Greg J. Fox, MB, BS, PhD, associate professor in respiratory medicine at Sydney Medical School in Australia and a co-author of the study, told Infectious Disease News. “WHO guidelines for screening identify a lack of high-quality evidence to support the use of contact investigation. They recommend it but have called for studies to show it is effective.”
Fox said the newly published findings address the need for evidence by not only showing that the intervention — which includes testing household contacts of TB patients — is effective but also feasible.
“We implemented this study through the TB control program in Vietnam — in 70 districts across the country. Therefore, we have shown that even in a relatively limited resource setting, it is possible to implement large-scale contact investigation,” he said.
WHO has adopted a strategy to end TB by the year 2030, but Fox and colleagues noted that the global incidence has declined just 1.4% per year since 2000 — well below targeted goals — and the disease affected more people in 2015 than any time in history. TB remains the world’s No. 1 infectious disease killer. Although WHO recently reported that TB deaths have declined 37% since 2000, the agency also noted several grim statistics, including that the disease is the leading cause of death related to antimicrobial resistance and the leading killer among patients with HIV.
Vietnam is a high-prevalence country, with 102,676 registered TB cases in 2015 and an additional 30,000 people estimated to be affected without receiving appropriate treatment, according to Fox and colleagues.
The researchers conducted a cluster-randomized controlled trial to evaluate the effectiveness of household-contact investigation compared with standard, passive measures. The study took place in districts in Vietnam with an average population of approximately 500,000 people in urban areas and 100,000 in rural areas. From October 2010 to June 2015, the researchers instructed health workers at 36 clinics and hospitals to perform the household-contact intervention plus standard passive case finding of TB cases or passive case finding alone.
In the intervention group, household contacts of patients with a positive TB test were invited for a clinical assessment and chest radiography at baseline, 6, 12 and 24 months, Fox and colleagues said. The primary outcome was the proportion of contacts who were registered as having the disease by Vietnam’s national TB program.
In all, 25,707 household contacts of 10,964 patients with pulmonary TB were enrolled, including 10,069 contacts in the intervention group. Among these contacts, 180 were registered as having TB — 1,788 cases per 100,000 population compared with 703 per 100,000 people in districts that used only passive case finding, making the relative risk for the primary outcome in the intervention group 2.5 (95% CI, 2-3.2).
The strategy also improved patient outcomes, including higher rates of treatment for those in the intervention group. Fox said another “surprising” post-hoc secondary outcome showed that mortality was reduced by 40% in the intervention group.
“Although the journal article does not emphasize this, it is potentially a major finding,” he said. “Tuberculosis is a major cause of mortality globally, and so the finding that mortality is reduced provides a strong rationale to scaling this approach up in other high-burden settings.” – Gerard Gallagher
Fox GJ, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1700209.
Disclosures: Fox reports receiving grants from Australia’s National Health and Medical Research Council during the study. Please see the study for all other authors’ relevant financial disclosures.