Diagnostic Test Accuracy in Childhood Pulmonary Tuberculosis: A Bayesian Latent Class Analysis

Abstract

Evaluation of tests for the diagnosis of childhood pulmonary tuberculosis (CPTB) is complicated by the absence of an accurate reference test. We present a Bayesian latent class analysis in which we evaluated the accuracy of 5 diagnostic tests for CPTB. We used data from a study of 749 hospitalized South African children suspected to have CPTB from 2009 to 2014. The following tests were used: mycobacterial culture, smear microscopy, Xpert MTB/RIF (Cepheid Inc.), tuberculin skin test (TST), and chest radiography. We estimated the prevalence of CPTB to be 27% (95% credible interval (CrI): 21, 35). The sensitivities of culture, Xpert, and smear microscopy were estimated to be 60% (95% CrI: 46, 76), 49% (95% CrI: 38, 62), and 22% (95% CrI: 16, 30), respectively; specificities of these tests were estimated in accordance with prior information and were close to 100%. Chest radiography was estimated to have a sensitivity of 64% (95% CrI: 55, 73) and a specificity of 78% (95% CrI: 73, 83). Sensitivity of the TST was estimated to be 75% (95% CrI: 61, 84), and it decreased substantially among children who were malnourished and infected with human immunodeficiency virus (56%). The specificity of the TST was 69% (95% CrI: 63%, 76%). Furthermore, it was estimated that 46% (95% CrI: 42, 49) of CPTB-negative cases and 93% (95% CrI: 82; 98) of CPTB-positive cases received antituberculosis treatment, which indicates substantial overtreatment and limited undertreatment.

Keywords: specificity; childhood pulmonary tuberculosis; diagnosis; latent class analysis; overtreatment; sensitivity.

Figure 1.

Heuristic model specifying prior beliefs of relations between latent and manifest variables. HIV, human immunodeficiency virus; TB, tuberculosis; TST, tuberculin skin test.

Figure 2.

Residual correlation plots for models 1–4 (A–D), South Africa, 2009–2014. Residual correlations are computed as the difference between observed and model-predicted correlations between each pair of tests: pair 1, liquid culture and Xpert MTB/RIF; pair 2, liquid culture and microscopy; pair 3, liquid culture and radiography; pair 4, liquid culture and tuberculin skin test; pair 5, Xpert MTB/RIF and microscopy; pair 6, Xpert MTB/RIF and radiography; pair 7, Xpert MTB/RIF and tuberculin skin test; pair 8, microscopy and radiography; pair 9, microscopy and tuberculin skin test; and pair 10, radiography and tuberculin skin test.

Figure 3.

Estimated sensitivity as a function of the random effect (latent class model 3), South Africa, 2009–2014. A) Microbiological tests; B) tuberculin skin test. HIV, human immunodeficiency virus.

Figure 4.

The probability of childhood pulmonary tuberculosis (CPTB) and the probability of treatment were estimated within quantiles of the posterior mean probabilities of CPTB for each child based on latent class model 3, South Africa, 2009–2014. Dashed lines are boundaries of quantiles.