Use of Xpert for the diagnosis of pulmonary tuberculosis in severely malnourished hospitalized Malawian children

Background: Pulmonary tuberculosis contributes to increased morbidity and mortality in severely malnourished children in endemic settings. Despite high clinical suspicion, few tuberculosis prevalence estimates exist in malnourished African children. Diagnostics such as Xpert MTB/RIF may help to determine pulmonary tuberculosis prevalence, however its performance in severely malnourished children is largely unknown. Methods: We conducted a prospective observational study evaluating Xpert compared to smear microscopy and liquid culture on induced sputums among severely malnourished children (aged 6 to 60 months) at Kamuzu Central Hospital in Lilongwe, Malawi. From February 1 to May 30, 2012, children who met World Health Organization 2006 guidelines for severe acute malnutrition were evaluated using clinical symptoms, tuberculin skin tests, chest radiographs, and induced sputums. National Institute of Health (NIH) consensus case definitions were used to estimate tuberculosis prevalence. Results: Three hundred severely malnourished children (median age 18.5 months, IQR 12.1-25.6) had one induced sputum performed; 295 (98.3%) received two. Fifty-two (17.6%) were HIV-infected. Over 25% had tuberculosis exposure with 48/297 (16.2%) reporting contact and 40/287 (13.9%) with positive TST. Two (0.7%) patients had confirmed tuberculosis by Xpert and culture, but only one had positive smear microscopy. Twenty (6.7%) patients fulfilled probable and 97 (66%) met possible tuberculosis NIH case definitions. Overall mortality was 9.7%. Conclusions: Microbiologic confirmation likely underestimates the prevalence of pulmonary tuberculosis in severely malnourished children. In our study, Xpert on induced sputums did not increase case finding. Future studies are needed using Xpert among targeted groups of severely malnourished children and on non-sputum specimens.