ABSTRACT
BACKGROUND: Subclinical pulmonary tuberculosis, which presents without recognisable symptoms, is frequently detected in community screening. However, the disease category is poorly clinically defined. We explored the prevalence of subclinical pulmonary tuberculosis according to different case definitions. METHODS: We did a one-stage individual participant data meta-analysis of nationally representative surveys that were conducted in countries with high incidence of tuberculosis between 2007 and 2020, that reported the prevalence of pulmonary tuberculosis based on chest x-ray and symptom screening in participants aged 15 years and older. Screening and diagnostic criteria were standardised across the surveys, and tuberculosis was defined by positive Mycobacterium tuberculosis sputum culture. We estimated proportions of subclinical tuberculosis for three case definitions: no persistent cough (ie, duration ≥2 weeks), no cough at all, and no symptoms (ie, absence of cough, fever, chest pain, night sweats, and weight loss), both unadjusted and adjusted for false-negative chest x-rays and uninterpretable culture results. FINDINGS: We identified 34 surveys, of which 31 were eligible. Individual participant data were obtained and included for 12 surveys (620 682 participants) across eight countries in Africa and four in Asia. Data on 602 863 participants were analysed, of whom 1944 had tuberculosis. The unadjusted proportion of subclinical tuberculosis was 59·1% (n=1149/1944; 95% CI 55·8-62·3) for no persistent cough and 39·8% (773/1944; 36·6-43·0) for no cough of any duration. The adjusted proportions were 82·8% (95% CI 78·6-86·6) for no persistent cough and 62·5% (56·6-68·7) for no cough at all. In a subset of four surveys, the proportion of participants with tuberculosis but without any symptoms was 20·3% (n=111/547; 95% CI 15·5-25·1) before adjustment and 27·7% (95% CI 21·0-36·4) after adjustment. Tuberculosis without cough, irrespective of its duration, was more frequent among women (no persistent cough: adjusted odds ratio 0·79, 95% CI 0·63-0·97; no cough: adjusted odds ratio 0·76, 95% CI 0·62-0·93). Among participants with tuberculosis, 29·1% (95% CI 25·2-33·3) of those without persistent cough and 23·1% (18·8-27·4) of those without any cough had positive smear examinations. INTERPRETATION: The majority of people in the community who have pulmonary tuberculosis do not report cough, a quarter report no tuberculosis-suggestive symptoms at all, and a quarter of those not reporting any cough have positive sputum smears, suggesting infectiousness. In high-incidence settings, subclinical tuberculosis could contribute considerably to the tuberculosis burden and to Mycobacterium tuberculosis transmission. FUNDING: Mr Willem Bakhuys Roozeboom Foundation.
ABSTRACT
BACKGROUND: Pulmonary tuberculosis infection can manifest in different states, including subclinical tuberculosis. It is commonly defined as confirmed tuberculosis without the classic symptoms (commonly, persistent cough for ≥2 weeks). This narrow definition likely poses limitations for surveillance and control measures. The aims of the current study were to characterize the clinical presentation of tuberculosis; estimate the prevalence of subclinical tuberculosis among individuals with bacteriologically confirmed tuberculosis, using various definitions; and investigate risk factors for subclinical as opposed to clinical tuberculosis in a population-based survey. METHODS: We conducted a secondary analysis of data from a nationally representative tuberculosis prevalence survey from Zambia in 2013-2014, in which participants were screened for tuberculosis based on chest radiographic findings and symptoms. Tuberculosis was defined as culture-positive or GeneXpert MTB/RIF test-positive sputum. Risk factors for subclinical tuberculosis were assessed by means of multivariable logistic regression. RESULTS: Of 257 participants with confirmed tuberculosis, 104 (40.5%) were without cough persisting ≥2 weeks. Only 23 (22.1%) of these did not present with any other common symptoms. Those without cough persisting ≥2 weeks frequently reported other symptoms, particularly chest pain (46.2%) and weight loss (38.5%); 36 (34.6%) reported experiencing other symptoms persisting ≥4 weeks. Female subjects were more likely to report no cough persisting ≥2 weeks, as were relatively wealthier individuals. CONCLUSIONS: The commonly used definition of subclinical tuberculosis includes a large proportion of individuals who have other tuberculosis-suggestive symptoms. Requiring cough ≥2 weeks for tuberculosis diagnosis likely misses many active tuberculosis infections and allows a large reservoir of likely transmissible tuberculosis to remain undetected.
