Mortality and Cause of Death in Children With Presumptive Disseminated Tuberculosis.

BACKGROUND AND OBJECTIVES: Children experience high tuberculosis (TB)-related mortality but causes of death among those with presumptive TB are poorly documented. We describe the mortality, likely causes of death, and associated risk factors among vulnerable children admitted with presumptive TB in rural Uganda. METHODS: We conducted a prospective study of vulnerable children, defined as <2 years of age, HIV-positive, or severely malnourished, with a clinical suspicion of TB. Children were assessed for TB and followed for 24 weeks. TB classification and likely cause of death were assessed by an expert endpoint review committee, including insight gained from minimally invasive autopsies, when possible. RESULTS: Of the 219 children included, 157 (71.7%) were <2 years of age, 72 (32.9%) were HIV-positive, and 184 (84.0%) were severely malnourished. Seventy-one (32.4%) were classified as "likely tuberculosis" (15 confirmed and 56 unconfirmed), and 72 (32.9%) died. The median time to death was 12 days. The most frequent causes of death, ascertained for 59 children (81.9%), including 23 cases with autopsy results, were severe pneumonia excluding confirmed TB (23.7%), hypovolemic shock due to diarrhea (20.3%), cardiac failure (13.6%), severe sepsis (13.6%), and confirmed TB (10.2%). Mortality risk factors were confirmed TB (adjusted hazard ratio [aHR] = 2.84 [95% confidence interval (CI): 1.19-6.77]), being HIV-positive (aHR = 2.45 [95% CI: 1.37-4.38]), and severe clinical state on admission (aHR = 2.45 [95% CI: 1.29-4.66]). CONCLUSIONS: Vulnerable children hospitalized with presumptive TB experienced high mortality. A better understanding of the likely causes of death in this group is important to guide empirical management.

Evaluation of OMNIgene Sputum and Ethanol Reagent for Preservation of Sputum Prior to Xpert and Culture Testing in Uganda.

Xpert MTB/RIF (Xpert) and culture are the most reliable methods for tuberculosis diagnosis but are still poorly accessible in many low-resource countries. We aimed to assess the effects of OMNIgene Sputum (OM-S) and ethanol in preserving sputum for Xpert and OM-S for mycobacterial growth indicator tube (MGIT) testing over periods of 15 and 8 days, respectively. Sputum samples were collected from newly diagnosed smear-positive patients. For Xpert, pooled samples were split into 5 aliquots: 3 for Xpert on days 0, 7, and 15 without additive and 2 with either OM-S or ethanol at day 15. For MGIT, 2 aliquots were tested without preservative and 2 with OM-S at 0 and 8 days. Totals of 48 and 47 samples were included in the analysis for Xpert and culture. With Xpert, using day 0 as a reference, untreated samples stored for 7 and 15 days showed concordances of 45/46 (97.8%) and 46/48 (95.8%). For samples preserved with OM-S or ethanol for 15 days compared with untreated samples processed at day 0 or after 15 days, OM-S concordances were 46/48 (95.8%) and 47/48 (97.9%), while those of ethanol were 44/48 (91.7%) and 45/48 (93.8%). With MGIT, concordances between untreated and OM-S-treated samples were 21/41 (51.2%) at day 0 and 21/44 (47.7%) at day 8. In conclusion, Xpert equally detected tuberculosis in OM-S-treated and untreated samples up to 15 days but showed slightly lower detection in ethanol-treated samples. Among OM-S-treated samples, MGIT positivity was significantly lower than in untreated samples at both time points.