A clinical scoring system to prioritise investigation for tuberculosis among adults attending HIV clinics in South Africa

Abstract

BackgroundThe World Health Organization (WHO) recommendation for regular tuberculosis (TB) screening of HIV-positive individuals with Xpert MTB/RIF as the first diagnostic test has major resource implications.ObjectiveTo develop a diagnostic prediction model for TB, for symptomatic adults attending for routine HIV care, to prioritise TB investigation.DesignCohort study exploring a TB testing algorithm.SettingHIV clinics, South Africa.ParticipantsRepresentative sample of adult HIV clinic attendees; data from participants reporting ≥1 symptom on the WHO screening tool were split 50:50 to derive, then internally validate, a prediction model.OutcomeTB, defined as “confirmed” if Xpert MTB/RIF, line probe assay or M. tuberculosis culture were positive; and “clinical” if TB treatment started without microbiological confirmation, within six months of enrolment.ResultsOverall, 79/2602 (3.0%) participants on ART fulfilled TB case definitions, compared to 65/906 (7.2%) pre-ART. Among 1133/3508 (32.3%) participants screening positive on the WHO tool, 1048 met inclusion criteria for this analysis: 52/515 (10.1%) in the derivation and 58/533 (10.9%) in the validation dataset had TB. Our final model comprised ART status (on ART > 3 months vs. pre-ART or ART < 3 months); body mass index (continuous); CD4 (continuous); number of WHO symptoms (1 vs. >1 symptom). We converted this to a clinical score, using clinically-relevant CD4 and BMI categories. A cut-off score of ≥3 identified those with TB with sensitivity and specificity of 91.8% and 34.3% respectively. If investigation was prioritised for individuals with score of ≥3, 68% (717/1048) symptomatic individuals would be tested, among whom the prevalence of TB would be 14.1% (101/717); 32% (331/1048) of tests would be avoided, but 3% (9/331) with TB would be missed amongst those not tested.ConclusionOur clinical score may help prioritise TB investigation among symptomatic individuals.

A clinical score for identifying active tuberculosis while awaiting microbiological results: Development and validation of a multivariable prediction model in sub-Saharan Africa

“…The predictive accuracy of this simple clinical score was compatible with, or even superior to, previously published prediction models that incorporated criteria including chest X-ray [12] (c-statistic = 0.70, 0.79), body mass index (BMI) [13,15] (c-statistic = 0.70), hemoglobin level [14,15] (c-statistic = 0.66), HIV viral load and ART [37] (c-statistic = 0.59, 0.69), CD4 + T cell count [12,13,37] (c-statistic = 0.70), and Karnofsky score [14] (c-statistic = 0.75). These measures may not be readily available in highly resource-constrained settings that may lack even reliable scales and stadiometers.…”

“…Most existing models for predicting active TB require equipment or infrastructure (e.g., radiology, laboratory testing, and calculations requiring a computer or smartphone) that is generally unavailable in clinical settings that also lack same-day microbiological testing for TB [12][13][14][15]. Thus, there exists a need for a prediction score that is simple enough to write on paper and calculate rapidly by hand.…”

Patient costs incurred by people living with HIV/AIDS prior to ART initiation in primary healthcare facilities in Gauteng, South Africa

“…This study was conducted as part of the XPHACTOR study, a prospective cohort study evaluating a risk-based algorithm to prioritise Xpert MTB/RIF testing among adults attending routine HIV care in South Africa [9]. HIV-positive pre-ART and ART patients were recruited from separate facilities providing HIV care.…”

Performance of verbal autopsy methods in estimating HIV-associated mortality among adults in South Africa

“… 15 (2) ‘XPHACTOR’ was an interventional cohort study investigating the use of Xpert MTB/RIF in a systematic sample of HIV-positive adults attending outpatient clinics for HIV care. 16 (3) ‘XTEND’ was a cluster-randomised trial evaluating the impact on mortality of Xpert MTB/RIF roll-out; it enrolled HIV-positive and HIV-negative adults who had sputum sent for TB investigation at 40 PHCs. 17 …”