Screening for TB in high school adolescents in a high burden setting in South Africa

Summary

Screening for tuberculosis (TB) disease is important for TB control and TB vaccine efficacy trials but this has not been evaluated in adolescents. We conducted a study to determine the prevalence of active TB and performance of specific screening tests for TB in adolescents in a high burden setting. Adolescents aged 12–18 years were recruited from high schools in a rural town in South Africa. Participants were screened for active TB using symptoms, household TB contact, positive interferon gamma release assay (IGRA) and positive tuberculin skin test (TST). Of 6363 adolescents recruited, 21 were newly diagnosed with TB of whom 19 were culture positive. After exclusions, the derived prevalence of smear positive TB was 16/5682 = 3/1000 (95% confidence interval (CI) 1–4/1000). The sensitivity of TST and IGRA for active TB were 85% (95% CI 62–100%) and 94% (95% CI 79–100%) respectively. None of the methods alone or in combination had positive predictive values greater than 2%. The screening tools evaluated in this study may not be practical for routine use owing to low positive predictive values but may be useful in TB vaccine clinical trials.

Introduction

Tuberculosis (TB) remains a significant public health problem globally.¹ While TB control programmes have previously focused on optimal cure rates of smear positive TB patients, active case finding is receiving increased attention as an important component of strategies aimed at TB elimination. Early and improved case detection are both components of the Global Plan to Stop TB.2, 3 In a different context, efficacy trials of new TB vaccines need effective methods to exclude cases of TB prior to study enrolment and to detect TB cases during follow up.

Based on TB control programme data, age distributions of TB incidence show adolescence to be a period of increasing incidence.4, 5 There are however no studies that have specifically investigated prevalence of active TB in adolescents. Knowledge of prevalent TB in adolescents is relevant to public health programmes since these cases represent a source of transmission. Resulting new infections in turn present a high risk of progressing to active TB.⁶

It has been shown that occurrence of TB in high burden settings is often due to exposure outside of the home environment.⁷ Thus, adolescents may become infected in the school environment owing to the presence of active TB cases and may rapidly progress to active TB while still at school, representing a further risk to others. Early diagnosis in adolescents, who have been described as having a high “force of infection”,⁸ is therefore important to reduce the risk of transmission in school settings where large numbers of adolescents congregate in closed spaces.

Adolescents are also an important target group for TB vaccine trials.⁹ Knowledge of prevalence would assist with planning for TB vaccine trials since it is important to know the burden of TB for calculating trial sample sizes.

The identification of prevalent cases requires effective screening tools. Tuberculosis screening has been evaluated in communities in Africa,10, 11, 12 amongst immigrants in a low burden setting¹³ and health workers.¹⁴ The World Health Organisation has also proposed strategies for TB screening in population-based surveys.¹⁵ However, we have found no studies that have investigated TB screening specifically in adolescents. In the context of TB vaccine clinical trials, the value of good screening tools would be to exclude cases of TB at enrolment prior to vaccination for safety reasons and to detect TB cases during follow up as case ascertainment is crucial to the success of efficacy trials. Low cost, efficient screening tools are therefore needed to make trials as cost effective as possible.

We thus conducted a study in adolescents to determine the prevalence of TB and the performance of various TB screening tools in detecting TB disease. As the routine use of the chest radiograph was not feasible in our setting, this was not included as a screening tool. Other publications on this study population include: (1) an examination of risk factors for latent TB infection based on the tuberculin skin test (TST) and QuantiFERON TB Gold (in-tube) (QFT) assay results at enrolment¹⁶; (2) a comparison of the predictive value of baseline TST and QFT for TB disease during follow-up¹⁷; (3) the determination of the predictive value of a QFT conversion for TB disease in a subset of participants who underwent extended follow up¹⁸; and (4) TB incidence in an adolescent cohort in South Africa (manuscript under review).