A Refined Symptom-Based Approach to Diagnose Pulmonary Tuberculosis in Children

Abstract

BACKGROUND. Tuberculosis control programs place an almost exclusive emphasis on adults with sputum smear-positive tuberculosis, because they are most infectious. However, children contribute a significant proportion of the global tuberculosis caseload and experience considerable tuberculosis-related morbidity and mortality, but few children in endemic areas have access to antituberculosis treatment. The diagnostic difficulty experienced in endemic areas with limited resources has been identified as a major factor contributing to poor treatment access. In general, there is a sense of scepticism regarding the potential value of symptom-based diagnostic approaches, because current clinical diagnostic approaches are often poorly validated. The natural history of childhood tuberculosis demonstrates that symptoms may offer good diagnostic value if they are well defined and if appropriate risk stratification is applied. This study aimed to determine the value of well-defined symptoms to diagnose childhood pulmonary tuberculosis in a tuberculosis-endemic area. METHODS. A prospective, community-based study was conducted in Cape Town, South Africa. Specific well-defined symptoms were documented in all children 2 weeks9 duration; study participants were thoroughly evaluated for tuberculosis. In addition, all of the children who received antituberculosis treatment during the study period were reviewed by the investigator, irrespective of study inclusion. This concurrent disease surveillance provided a comprehensive overview of all of the childhood tuberculosis cases, allowing accurate assessment of the possible disadvantages associated with this symptom-based diagnostic approach. In the absence of an acceptable gold standard test, optimal case definition is an important consideration. Children were categorized as “bacteriologically confirmed tuberculosis,” “radiologically certain tuberculosis,” “probable tuberculosis,” or “not tuberculosis.” Bacteriologically confirmed tuberculosis was defined as the presence of acid-fast bacilli on sputum microscopy and/or Mycobacterium tuberculosis cultured from a respiratory specimen. Radiologically certain tuberculosis was defined as agreement between both independent experts that the chest radiograph indicated certain tuberculosis in the absence of bacteriologic confirmation. Probable tuberculosis was defined as the presence of suggestive radiologic signs and good clinical response to antituberculosis treatment in the absence of bacteriologic confirmation or radiologic certainty. Good clinical response was defined as complete symptom resolution and weight gain of ≥10% of body weight at diagnosis, within 3 months of starting antituberculosis treatment. Not tuberculosis was defined as spontaneous symptom resolution or no response to antituberculosis therapy in the absence of bacteriologic confirmation or radiologic signs suggestive of tuberculosis. Pulmonary tuberculosis was defined as a symptomatic child with: (1) bacteriologically confirmed tuberculosis, (2) radiologically confirmed tuberculosis, or (3) probable tuberculosis (as defined), excluding isolated pleural effusion. RESULTS. In total, 1024 children were referred for evaluation. Resolving symptoms were reported in 596 children (58.2%); 428 (41.8%) children with persistent, nonremitting symptoms at evaluation were investigated for tuberculosis. Pulmonary tuberculosis was diagnosed in 197 children; 96 were categorized as bacteriologically confirmed tuberculosis, 75 as radiologically certain tuberculosis, and 26 as probable tuberculosis. Combining a persistent nonremitting cough of >2 weeks9 duration, documented failure to thrive (in the preceding 3 months), and fatigue provided reasonable diagnostic accuracy in HIV-uninfected children (sensitivity: 62.6%; specificity: 89.8%; positive predictive value: 83.6%); the performance was better in the low-risk group (≥3 years; sensitivity: 82.3%; specificity: 90.2%; positive predictive value: 82.3%) than in the high-risk group ( DISCUSSION. The combined presence of 3 well-defined symptoms at presentation (persistent, nonremitting cough of >2 weeks9 duration; objective weight loss [documented failure to thrive] during the preceding 3 months; and reported fatigue) provided good diagnostic accuracy in HIV-uninfected children ≥3 years of age, with clinical follow-up providing additional value. The approach performed less well in children CONCLUSIONS. Pulmonary tuberculosis can be diagnosed with a reasonable degree of accuracy in HIV-uninfected children using a simple symptom-based approach. This offers the exciting prospect of improving treatment access for children, particularly in resource-limited settings where current access to antituberculosis treatment is poor.