Mortality in South African Children and Adolescents Routinely Treated for Tuberculosis

Abstract

BACKGROUND: In South Africa, tuberculosis (TB) is a leading cause of death among those <20 years of age. We describe changes in TB mortality among children and adolescents in South Africa over a 13-year period, identify risk factors for mortality, and estimate excess TB-related mortality. METHODS: Retrospective analysis of all patients <20 years of age routinely recorded in the national electronic drug-susceptible TB treatment register (2004–2016). We developed a multivariable Cox regression model for predictors of mortality and used estimates of mortality among the general population to calculate standardized mortality ratios (SMRs). RESULTS: Between 2004 and 2016, 729 463 children and adolescents were recorded on TB treatment; 84.0% had treatment outcomes and 2.5% (18 539) died during TB treatment. The case fatality ratio decreased from 3.3% in 2007 to 1.9% in 2016. In the multivariable Cox regression model, ages 0 to 4, 10 to 14, and 15 to 19 years (compared with ages 5 to 9 years) were associated with increased risk of mortality, as was HIV infection, previous TB treatment, and extrapulmonary involvement. The SMR of 15 to 19-year-old female patients was more than double that of male patients the same age (55.3 vs 26.2). Among 10 to 14-year-olds and those who were HIV-positive, SMRs increased over time. CONCLUSIONS: Mortality in South African children and adolescents treated for TB is declining but remains considerable, with 2% dying during 2016. Adolescents (10 to 19 years) and those people living with HIV have the highest risk of mortality and the greatest SMRs. Interventions to reduce mortality during TB treatment, specifically targeting those at highest risk, are urgently needed.

The Impact of Tuberculosis on the Well-Being of Adolescents and Young Adults

“…In most published reports, ≥80% of AYAs are treated successfully for drug-susceptible TB. Most adolescents with unfavorable outcomes are lost to follow-up; <5% die [10,45]. An analysis of drug-susceptible TB treatment outcomes between 2004 and 2016 in South Africa demonstrated age-disaggregated case-fatality (CFRs) between 2.3 and 4.3 for adolescents; notably, the CFR peaked for boys in mid-adolescence and for girls in late adolescence [45].…”

“…Most adolescents with unfavorable outcomes are lost to follow-up; <5% die [10,45]. An analysis of drug-susceptible TB treatment outcomes between 2004 and 2016 in South Africa demonstrated age-disaggregated case-fatality (CFRs) between 2.3 and 4.3 for adolescents; notably, the CFR peaked for boys in mid-adolescence and for girls in late adolescence [45]. In the same South African cohort, children and adolescents (0-19 years old) with HIV and TB had a CFR of 4.8 if they were receiving ART and 6.3 if they were not on ART; in comparison, children and adolescents without HIV had a CFR of 1.0 from TB [45].…”

Tuberculosis in Adolescents and Young Adults: Emerging Data on TB Transmission and Prevention among Vulnerable Young People

“…Increased TB risk for females relative to males appears to peak at mid-adolescence [2,10]. Sex differences are also seen in TB-related mortality, which may intersect with higher vulnerability to HIV among female AYA [2,10,12]. A study in Cape Town, South Africa, a region with high TB and HIV prevalence, found that of adolescents aged 15-19 years with drug-susceptible TB, female adolescents had more than twice the risk of mortality than male adolescents [12].…”

“…Among young adults and older individuals, the higher TB risk shifts to males [2,10]. Reasons for these shifting sex differences remain unclear but may reflect a combination of factors [2,10,12]. Proposed influences include factors increasing susceptibility to TB among female adolescents (due to physiologic changes at menarche, a higher incidence of HIV infection among female AYA, TB risks associated with pregnancy, and/or other drivers yet to be identified) or factors resulting in undiagnosed TB among male adolescents, who might be less likely to access care to receive a TB diagnosis and/or may face higher mortality from interpersonal violence or other noninfectious causes [2,10,12].…”

“…Disruptions may be especially acute for AYA with drug-resistant TB, who may undergo prolonged enforced isolation or hospitalization [22,25,26]. As a result, AYA with TB infection and disease experience higher rates of loss to follow-up (LTFU) than either younger children or older adults [12,[27][28][29][30]. A study in Botswana found that adolescents aged 10-19 years were lost from TB care more often than young adults aged 20-24 years and at twice the rate of older adults [27].…”