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. 2021 Apr;147(4):e2020032490.
doi: 10.1542/peds.2020-032490. Epub 2021 Mar 10.

Mortality in South African Children and Adolescents Routinely Treated for Tuberculosis

Muhammad Osman  1 , Karen du Preez  2 , James A Seddon  2   3 , Mareli M Claassens  2   4 , Rory Dunbar  2 , Sicelo S Dlamini  5 , Alex Welte  6 , Pren Naidoo  2 , Anneke C Hesseling  2
Affiliations

Mortality in South African Children and Adolescents Routinely Treated for Tuberculosis

Muhammad Osman et al. Pediatrics. 2021 Apr.

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.

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Conflict of interest statement

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Overall CFR and stratification by age category for children and adolescents treated for drug-susceptible TB, South Africa, 2004–2016. A, Overall CFR. B, Stratification by age category.
FIGURE 2
FIGURE 2
CFR of all children and adolescents treated for drug-susceptible TB in South Africa between 2004 and 2016, stratified by age and sex.
FIGURE 3
FIGURE 3
Kaplan-Meier survival curve stratified by HIV and ART status of children and adolescents on drug-susceptible TB treatment between 2013 and 2016 in South Africa.
FIGURE 4
FIGURE 4
SMRs of children and adolescents on drug-susceptible TB treatment in South Africa, 2004–2016. SMR is the ratio of observed TB deaths to the expected deaths and is based on the Thembisa estimates of mortality rates for the general population. Expected mortality is based on the product of the age- and sex-specific population estimates of mortality rates from Thembisa and the person-time in the TB cohort.
FIGURE 5
FIGURE 5
SMRs by HIV status of children and adolescents on drug-susceptible TB treatment in South Africa, 2013–2016. SMR is the ratio of observed TB deaths to the expected deaths and is based on the Thembisa estimates of mortality rates for the general population. Expected mortality is based on products of the HIV-positive and HIV-negative population estimates of mortality rates (regardless of age) from the Thembisa model and the person-time in the TB cohort.
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References

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