Patients with chest X-ray changes suggestive of active tuberculosis (TB) whose microbiological test results are initially negative have an increased risk for disease progression, according to meta-analysis findings published in The Lancet Respiratory Medicine.
Researchers sought to quantify and examine TB disease progression, regression, and transition using the natural history of the disease as the conceptual framework.
They therefore conducted a systematic review and meta-analysis of studies from the pre-chemotherapy era to determine which transitions could be adequately characterized by the literature and thus provide parameters for the rate of TB progression and regression along the disease spectrum.
The reviewers electronically searched MEDLINE, EMBASE, and Web of Science for relevant articles published in English and German from database inception (1946, 1947, and 1900, respectively) to December 31, 1960. A manual search was done in Index Medicus for articles from January 1, 1903, to December 31, 1945. Other relevant literature outside these date ranges were also reviewed.
Included studies had a longitudinal cohort of at least 25 adolescents (10 years of age or older), adults, or both, who were followed up for at least 12 months after a positive tuberculin skin test following recent tuberculosis exposure, radiographic abnormalities suggestive of tuberculosis, or positive microbiology for tuberculosis. The meta-analysis included 22 English and 2 German studies, with 139,063 participants from 34 cohorts.
A better understanding of the natural history of pulmonary tuberculosis, including the risk of progression in relation to radiological findings, could improve estimates of the global disease burden and inform the development of clinical guidelines and policies for treatment and prevention.
In analysis of 24 cohorts with abnormal chest radiography but no evidence of Mycobacterium tuberculosis on respiratory sampling at baseline (11,185 participants), microbiologically detectable incident disease occurred in 1% (97 of 6990) to 58% (88 of 152) of individuals, during a median follow-up of 34.5 months (interquartile range [IQR], 24-60).
The annualized transition rate from microbiologically negative to microbiologically positive disease was 10% (95% CI, 6.2-13.3) for 9 cohorts with active changes on radiography and 1% (95% CI, 0.3-1.8) in 7 cohorts with inactive changes on radiography. During a 3-year period, the annual rate of progression from microbiologically negative to positive disease in patients with active TB changes was 26% (17-35) vs 3% (1-5) in patients with inactive TB changes. The annual incidence for cohorts that had mixed radiographic changes was 6% (1.5-11.1).
Data regarding symptom status were provided for 11 cohorts. Among the 9 cohorts with active TB changes on radiography, 3 comprised symptomatic individuals (n=177). This subgroup had progression at an annualized rate of 12% (95% CI, 2.7-20.8).
A total of 6 cohorts included follow-up for 1024 participants with evidence of M tuberculosis in baseline respiratory samples and assessed the proportion who transitioned to a microbiologically undetectable state without treatment or intervention, with a median follow-up of 34.5 months (IQR, 13-54). The transition occurred at an annualized rate of 18% (95% CI, 3.0-33.7), although considerable heterogeneity was observed. When the meta-analysis was restricted to prospective studies, the annualized rate was 12% (6.8-18.0) with reduced statistical heterogeneity (I² =35.1%).
Among several limitations, HIV has a significant role in the epidemiology of tuberculosis in certain settings, and 22 of the 24 included studies were conducted before the virus was discovered. In addition, the studies were included from a wide span of years, and the findings could be affected by publication bias.
“A better understanding of the natural history of pulmonary tuberculosis, including the risk of progression in relation to radiological findings, could improve estimates of the global disease burden and inform the development of clinical guidelines and policies for treatment and prevention,” the study authors stated.