Sensitivity and specificity of WHO’s recommended four-symptom screening rule for tuberculosis in people living with HIV: A systematic review and meta-analysis


BACKGROUND: Since 2011, WHO recommends a four-symptom screening rule to exclude active tuberculosis in people living with HIV before starting tuberculosis preventive treatment (ie, absence of current cough, weight loss, night sweats, or fever). We assessed the sensitivity and specificity of the screening rule among people living with HIV based on antiretroviral therapy (ART) status and the added contribution of chest radiography. METHODS: We did a systematic review and meta-analysis. We searched PubMed, Embase, and the Cochrane Library from Jan 1, 2011, to March 12, 2018, for studies published after the WHO issued recommendations on the use of the four-symptom screening rule. We also searched abstracts from relevant international conferences. We included studies that collected sputum or any specimens (eg, urine, blood, or fine-needle aspirates from lymph nodes) from people with HIV regardless of signs or symptoms. Case-control studies were excluded because they are prone to bias. Active tuberculosis was diagnosed with bacteriological confirmation by culture or Xpert MTB/RIF of any specimens. Two investigators extracted the data, including age, sex, and ART status. We calculated sensitivity, specificity, and 95% CI. When at least four studies were available, we estimated pooled sensitivity and specificity using random and effects bivariate models; otherwise we used univariate random-effects models. FINDINGS: Of 4615 records identified by the search, 21 were included in the review (involving 15 427 people including 1559 with active tuberculosis). 18 eligible studies were included in the final meta-analysis. Seven studies provided data on people receiving ART. The pooled sensitivity of the four-symptom screening rule was lower for 4640 people on ART (51.0%, 95% CI 28.4-73.2) than for 8664 who were ART-naive (89.4%, 83.0-93.5). Pooled specificity for those on ART was 70.7% (95% CI 47.8-86.4) and for ART-naive people was 28.1% (18.6-40.1). On the basis of data from 646 individuals in two studies, the addition of any abnormal chest radiographic findings in people on ART improved sensitivity from 52.2% (95% CI 38.0-66.0) to 84.6% (69.7-92.9) but decreased specificity from 55.5% (95% CI 51.8-59.2) to 29.8% (26.3-33.6). INTERPRETATION: Our review suggested a lower sensitivity of the WHO four-symptom screening rule among people with HIV who are on ART than in those who are ART naive. The addition of chest radiography could improve the screening rule in people living with HIV who are on ART, provided it does not pose a barrier to preventive treatment. FUNDING: None


Hamada Y, Lujan J, Schenkel K, Ford N, Getahun H




  • Population(s)
    • General HIV+ population
  • Engagement and Care Cascade
    • Treatment
  • Co-infections
    • Tuberculosis


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