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Younger age, coinfection with HIV increases mortality risk for children with TB
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Children who do not receive appropriate and timely treatment for tuberculosis, especially those aged younger than 5 years, have an elevated risk for death, according to recent study findings.
In addition, children coinfected with HIV and TB exhibited a significantly higher mortality risk, even when receiving anti-TB treatments.
“Given that so many children with [TB] are never diagnosed, estimation of childhood [TB] mortality presents unique challenges,” Helen E. Jenkins, PhD, from the department of biostatistics at the Boston University School of Public Health, and colleagues wrote. “Cohort studies from the past three decades have included very few children who did not receive [TB] treatment. Mortality … estimates often rely on vital registration data, but attribution of deaths to undiagnosed [TB] posthumously is hampered by autopsy costs and the unreliability of vital record and verbal autopsy.”
To provide better comprehension of the mortality risks associated with TB among children, Jenkins and colleagues performed the first systematic review and meta-analysis of the available literature to estimate case fatality ratios stratified by treatment, age group and HIV infection. The researchers searched PubMed and Embase for reports including terms related to TB, children, mortality and population representativeness published before August 12, 2016.
In addition, the researchers divided the reports into three eras: the pre-treatment era included studies published prior to 1946 before streptomycin was available; 1946 to 1980 were classified as the middle era, during which the researchers assumed some children would receive appropriate treatment; and studies after 1980 were considered recent era. The researchers concluded that most children had received TB treatment in the recent era because many countries adopted the short-course model providing the directly observed treatment at the beginning of the 1980s.
However, many children in TB endemic areas infected with HIV were not appropriately treated for TB or went undiagnosed altogether. The researchers identified 31 papers in the systemic meta-analysis, which comprised 35 datasets and included 82,436 children, of whom 9,274 died of disease. Among children with TB in the pre-treatment era, the pooled case fatality ratio was 21.9% (95% CI, 18.1-26.4). In addition, children aged between infancy and 4 years had a greater mortality rate than children aged 5 to 14 years (43.6% [95% CI, 36.8-50.6] vs. 14.9% [95% CI, 11.5-19.1]).
Moreover, in HIV-infected children who received TB treatment prior to ART access, the case fatality ratio was 14.3% (95% CI, 7.4-24.1); however, among children who received TB treatment and had access to ART, mortality rates were still higher compared with children without HIV who received appropriate TB treatment (3.4% [95% CI, .7-9.6] vs. 0.4% [95% CI, 0.3-0.7]).
“The findings of our systematic review and meta-analysis suggest that the risk of death in children with [TB] is particularly high in children also infected with HIV and children who do not receive [TB] treatment, showing the urgent need to extend [TB] treatment to children in [TB] endemic areas,” the researchers wrote. “Our findings point to a large and invisible burden of preventable child deaths related to [TB], particularly in areas with uncontrolled [TB] transmission where children have poor access to appropriate care.”
In an accompanying editorial, Jeffrey R. Starke, MD, professor of pediatrics at Baylor College of Medicine and Infectious Diseases in Children Editorial Board member, wrote that Jenkins and colleagues’ systematic meta-analysis described that many children are not being diagnosed on time or at all for TB, and that solutions to the lack in screening and therapy methods need to come from within government powers.
“The solutions ultimately will be local, so national [TB] programs need to develop plans and provide resources for this effort,” Stark wrote. “What is needed most is the political will within the [TB] community to finally address the needs of children.” – by Kate Sherrer
Disclosure: Jenkins reports receiving funding from the U.S. National Institutes of Health award #K01AI102944; and Yuen, Rodriguez and Becerra report funding from Janssen Global Public Health. All other authors report no relevant financial disclosures.
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