HIV matters when diagnosing TB in young children: an ancillary analysis in children enrolled in the INPUT stepped wedge cluster randomized study

Abstract

Background Children under age five years, particularly those living with HIV (CLHIV), are at risk for rapid progression of tuberculosis (TB). We aimed to describe TB clinical presentations, diagnostic pathways and treatment outcomes in CLHIV compared to children without HIV in Cameroon and Kenya. Methods This sub-analysis of a cluster-randomized trial evaluating the integration of pediatric TB services from May 2019 to March 2021 enrolled children age < 5 years with TB. We estimated the HIV infection rate with 95% confidence interval (CI). We compared TB clinical presentations, diagnostic pathways and treatment outcomes in CLHIV and children without HIV. Finally, we investigated whether HIV infection was associated with a shorter time to TB diagnosis (≤ 3 months from symptoms onset) after adjusting for covariates. Univariable and multivariable logistic regression analysis were performed with adjusted odds ratios (AORs) presented as measures of the association of covariates with HIV status and with shorter time to TB diagnosis. Results We enrolled 157 children with TB (mean age was 1.5 years) and 22/157 (14.0% [9.0-20.4%]) were co-infected with HIV. CLHIV were more likely to initially present with acute malnutrition (AOR 3.16 [1.14–8.71], p = 0.027). Most TB diagnoses (140/157, 89%) were made clinically with pulmonary TB being the most common presentation; however, there was weak evidence of more frequent bacteriologic confirmation of TB in CLHIV, 18% vs. 9% (p = 0.067), due to the contribution of lateral-flow urine lipoarabinomannan to the diagnosis. HIV positivity (AOR: 6.10 [1.32–28.17], p = 0.021) was independently associated with a shorter time to TB diagnosis as well as fatigue (AOR: 6.58 [2.28–18.96], p = 0.0005), and existence of a household contact diagnosed with TB (AOR: 5.60 [1.58–19.83], p = 0.0075), whereas older age (AOR: 0.35 [0.15–0.85], p = 0.020 for age 2–5 years), night sweats (AOR: 0.24 [0.10–0.60], p = 0.0022) and acute malnutrition (AOR: 0.36 [0.14–0.92], p = 0.034) were associated with a delayed diagnosis. The case fatality rate was 9% (2/22) in CLHIV and 4% (6/135) in children without HIV, p = 0.31. Conclusions These results altogether advocate for better integration of TB services into all pediatric entry points with a special focus on nutrition services, and illustrate the importance of non-sputum-based TB diagnostics especially in CLHIV. Trial registration NCT03862261, first registration 05/03/2019.

Mortality of children and adolescents co-infected with tuberculosis and HIV: a systematic review and meta-analysis

“…A comprehensive search of databases yielded a total of 6936 publications. Out of these, 37 studies [13–15,18–51] encompassing data from 115 541 children and adolescents were deemed suitable for inclusion in the systematic review and meta-analysis (Table 1 and Fig. 1).…”

“…This study specifically targeted the population of children and adolescents with HIV-TB co-infection, encompassing a total of 37 studies involving 115 541 individuals. During the follow-up period, the estimated overall mortality rate for children and adolescents with HIV-TB co-infection was found to be 16% (95% CI [13][14][15][16][17][18][19][20]. Individuals solely infected with TB had a combined mortality rate of 4% (95% CI 3-7), while those solely infected with HIV was 6% (95% CI 3-13).…”

“…The duration of the follow-up period varied from 3 months to 10 years. During the follow-up period, the pooled HIV-TB co-infection mortality among children and adolescents was 16% (95% CI [13][14][15][16][17][18][19][20] with studyspecific mortality ranging from 9% to 48% (Fig. 2).…”

“…A total of seven studies [21,24,25,33,38,43,47] provided data on mortality rates among children and adolescents with HIV-TB co-infection across various age groups. The pooled mortality rates were 32% (95% CI [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] for those aged <12 months, 14% (95% CI [10][11][12][13][14][15][16][17][18][19] for the 1-5 years age group, 15% (95% CI 12-17) for the 5-10 years age group, and 16% (95% CI [13][14][15][16][17][18][19][20] for those aged over 10 years old (Figure 4, Supplemental Digital Content, http://links.lww.com/QAD/D142). As illustrated in Fig.…”