NEJM study suggests testing everyone, regardless of symptoms, can reduce prevalence.
The World Health Organization (WHO) releases its 2019 “Global Tuberculosis (TB) Report” tomorrow, and though the worldwide public health community can still achieve the agency’s “End TB Strategy” objectives by 2030, several hurdles need to be cleared.
Among them: Establishing effective, and widely available screening and evaluation protocols, particularly in resource-deprived regions around the world.
To that end, the authors of an analysis published on October 3rd by the New England Journal of Medicine (NEJM) may have a solution: a screening protocol they call Active Case Finding for Tuberculosis 3 (ACT3). The “community-wide active case-finding intervention” uses a rapid nucleic acid amplification test (Xpert MTB/RIF, Cepheid) to detect Mycobacterium tuberculosis in “spontaneously expectorated sputum samples” collected annually from all persons 15 years of age or older, regardless of whether or not they have disease symptoms, for a 3-year period.
The Australia-based research team wrote, “The application of the Xpert MTB/RIF test as the initial diagnostic tool in this trial, in place of the more conventional plain chest radiograph, proved to be feasible… [but t]he generalizability of [our] findings needs to be assessed in other settings and populations, as does the feasibility of scaling up screening with the nucleic acid amplification tests… The role of alternative first-stage screening tests, such as less expensive or more sensitive nucleic acid amplification tests performed on sputum samples, blood tests, or chest radiography, including the possible use of artificial intelligence algorithms to interpret the findings, needs to be evaluated, as does the effect of alternative schedules for screening… and the appropriate duration of the screening period.”
For the NEJM assessment, the ACT3 researchers performed a cluster-randomized controlled trial in Ca Mau Province, Vietnam, with participants 15 years of age or older residing in 60 intervention and 60 nonintervention (or control) clusters (subcommunes). Study subjects in the intervention communities were screened for pulmonary TB and whether or not they presented with symptoms, annually for 3 years, beginning in 2014, using rapid nucleic acid amplification testing of spontaneously expectorated sputum samples. The authors then calculated prevalence of TB infection among children born in 2012, as assessed by an interferon gamma release assay in the fourth year.
In all, the authors tested 42,150 participants in the intervention group and 41,680 participants in the control group. A total of 53 participants in the intervention group (incidence: 126 per 100,000 population) and 94 participants in the control group (incidence 226 per 100,000 population) had pulmonary TB. They noted that the prevalence of TB infection in children born in 2012 was 3.3% in the intervention group and 2.6% in the control group. Based on the prevalence ratio for microbiologically confirmed TB in the intervention group vs the control group (0.56), the team concluded that the number of persons needed to have been screened annually for 3 years to prevent 1 prevalent case of TB in the fourth year was 1002.
“The incremental effect of the intervention observed in our trial, if converted to an annualized rate of decline in TB prevalence, would be nearly 15% per annum during the implementation of annual active screening, which is higher than the 3% to 7% annual rate of decline observed in countries where 2 or more prevalence surveys have been conducted and also higher than the current worldwide rate of decline in incidence, estimated by the WHO to be 2% per annum,” they wrote. “Hence, this trial provides evidence to support the implementation of community-wide active case finding as an intervention to substantially accelerate progress toward the goal of TB elimination. However, further research is required to clarify the appropriate type, duration, and timing of screening, the effect on disease transmission, and the durability of the benefits.”
The End TB Strategy hopes to achieve an 80% reduction in new TB cases and a 90% reduction in TB-related deaths by 2030. As the authors of the NEJM paper note, WHO data as of 2018 indicates that new TB diagnoses are declining at a rate of roughly 2% annually; to reach the stated goals, though, that rate needs to be closer to 5%, according to the 2018 “Global TB Report.” Meanwhile, here in the United States, statistics released recently by the US Centers for Disease Control and Prevention (CDC) suggest that there were 9025 TB cases reported domestically in 2018, a 0.7% decrease from 2017.
Clearly, new screening protocols are needed—if not in America, then certainly elsewhere. Let’s hope the NEJM research is a sign the world is getting 1 step closer to solving its TB problem.