A multi-parameter diagnostic clinical decision tree for the rapid diagnosis of tuberculosis in HIV-positive patients presenting to an emergency centre

Abstract

Background: Early diagnosis is essential to reduce the morbidity and mortality of HIV-associated tuberculosis. We developed a multi-parameter clinical decision tree to facilitate rapid diagnosis of tuberculosis using point-of-care diagnostic tests in HIV-positive patients presenting to an emergency centre. Methods: A cross-sectional study was performed in a district hospital emergency centre in a high-HIV-prevalence community in South Africa. Consecutive HIV-positive adults with ≥1 WHO tuberculosis symptoms were enrolled over a 16-month period. Point-of-care ultrasound (PoCUS) and urine lateral flow lipoarabinomannan (LF-LAM) assay were done according to standardized protocols. Participants also received a chest X-ray. Reference standard was the detection of Mycobacterium tuberculosis using Xpert MTB/RIF or culture. Logistic regressions models were used to investigate the independent association between prevalent microbiologically confirmed tuberculosis and clinical and biological variables of interest. A decision tree model to predict tuberculosis was developed using the classification and regression tree algorithm. Results: There were 414 participants enrolled: 171 male, median age 36 years, median CD4 cell count 86 cells/mm3. Tuberculosis prevalence was 42% (n=172). Significant variables used to build the classification tree included ≥2 WHO symptoms, antiretroviral therapy use, LF-LAM, PoCUS independent features (pericardial effusion, ascites, intra-abdominal lymphadenopathy) and chest X-ray. LF-LAM was positioned after WHO symptoms (75% true positive rate, representing 17% of study population). Chest X-ray should be performed next if LF-LAM is negative. The presence of ≤1 PoCUS independent feature in those with ‘possible or unlikely tuberculosis’ on chest x-ray represented 47% of non-tuberculosis participants (true negative rate 83%). In a prediction tree which only included true point-of-care tests, a negative LF-LAM and the presence of ≤2 independent PoCUS features had a 71% true negative rate (representing 53% of sample). Conclusions: LF-LAM should be performed in all adults with suspected HIV-associated tuberculosis (regardless of CD4 cell count) presenting to the emergency centre.