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

Abstract

Background: The 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.

Objective: To develop a diagnostic prediction model for TB, for symptomatic adults attending for routine HIV care, to prioritise TB investigation.

Design: Cohort study exploring a TB testing algorithm.

Setting: HIV clinics, South Africa.

Participants: Representative 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.

Outcome: TB, 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.

Results: Overall, 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.

Conclusion: Our clinical score may help prioritise TB investigation among symptomatic individuals.

Fig 1. XPHACTOR study flow.

¹ High priority (any of: current cough, fever ≥ 3 weeks, body mass index (BMI) <18.5 kg/m², CD4 <100x10⁶/l, measured weight loss ≥10% in preceding 6 months, or other feature raising high clinical suspicion of TB); medium priority (any of: fever < 3 weeks, night sweats, measured weight loss <10% in preceding 6 months); low priority = no TB symptoms. ² Samples tested with Xpert MTB/RIF at the end of the study. ³ High priority (any of: current cough, fever ≥ 3 weeks, night sweats ≥ 4 weeks, body mass index (BMI) <18.5 kg/m², CD4 <100x10⁶/l, measured weight loss ≥10% in preceding 6 months, or other feature raising high clinical suspicion of TB); medium priority (any of: fever < 3 weeks, night sweats <4 weeks, measured weight loss <10% in preceding 6 months); low priority = no TB symptoms.

Fig 2. Flow chart of study participants.

¹ 28/2227 TB diagnosed within six months of enrolment (25 confirmed TB and 3 clinical TB), of whom 25 on ART and 3 pre-ART. ² 4/191 confirmed TB diagnosed within six months of enrolment, all pre-ART BMI = body mass index. IPT = Isoniazid preventive therapy. WHO tool negative = self-report of absence of all of: current cough, fever, night sweats and unintentional weight loss.

Fig 3. Calibration plot of final prediction model in derivation and validation datasets.

Fig 4. Performance of clinical score at different cut-offs offs (derivation and validation datasets combined; N = 1048).

NPV = negative predictive value. AUROC = area under the receiver-operating characteristic curve.

Fig 5. Clinical score and prevalence of TB.