Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies.
BACKGROUND
The World Health Organization recommends the screening of all people living with HIV for tuberculosis (TB) disease, followed by TB treatment, or isoniazid preventive therapy (IPT) when TB is excluded. However, the difficulty of reliably excluding TB disease has severely limited TB screening and IPT uptake in resource-limited settings. We conducted an individual participant data meta-analysis of primary studies, aiming to identify a sensitive TB screening rule.


RESULTS
We identified 12 studies that had systematically collected sputum specimens regardless of signs or symptoms, at least one mycobacterial culture, clinical symptoms, and HIV and TB disease status. Bivariate random-effects meta-analysis and the hierarchical summary relative operating characteristic curves were used to evaluate the screening performance of all combinations of variables of interest. TB disease was diagnosed in 557 (5.8%) of 9,626 people living with HIV. The primary analysis included 8,148 people living with HIV who could be evaluated on five symptoms from nine of the 12 studies. The median age was 34 years. The best performing rule was the presence of any one of: current cough (any duration), fever, night sweats, or weight loss. The overall sensitivity of this rule was 78.9% (95% confidence interval [CI] 58.3%-90.9%) and specificity was 49.6% (95% CI 29.2%-70.1%). Its sensitivity increased to 90.1% (95% CI 76.3%-96.2%) among participants selected from clinical settings and to 88.0% (95% CI 76.1%-94.4%) among those who were not previously screened for TB. Negative predictive value was 97.7% (95% CI 97.4%-98.0%) and 90.0% (95% CI 88.6%-91.3%) at 5% and 20% prevalence of TB among people living with HIV, respectively. Abnormal chest radiographic findings increased the sensitivity of the rule by 11.7% (90.6% versus 78.9%) with a reduction of specificity by 10.7% (49.6% versus 38.9%).


CONCLUSIONS
Absence of all of current cough, fever, night sweats, and weight loss can identify a subset of people living with HIV who have a very low probability of having TB disease. A simplified screening rule using any one of these symptoms can be used in resource-constrained settings to identify people living with HIV in need of further diagnostic assessment for TB. Use of this algorithm should result in earlier TB diagnosis and treatment, and should allow for substantial scale-up of IPT.
World Health Organization, Geneva, Switzerland. getahunh@who.int
Haileyesus
H
Getahun
Wanitchaya
W
Kittikraisak
Charles M
CM
Heilig
Elizabeth L
EL
Corbett
Helen
H
Ayles
Kevin P
KP
Cain
Alison D
AD
Grant
Gavin J
GJ
Churchyard
Michael
M
Kimerling
Sarita
S
Shah
Stephen D
SD
Lawn
Robin
R
Wood
Gary
G
Maartens
Reuben
R
Granich
Anand A
AA
Date
Jay K
JK
Varma
D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D001210:Asia, Southeastern / Q000453:epidemiology; D015897:Comorbidity; D003371:Cough / Q000453:epidemiology; D003906:Developing Countries; D005260:Female; D005334:Fever / Q000453:epidemiology; D015658:HIV Infections / Q000453:epidemiology*; D006295:Health Resources / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000706:statistics & numerical data*; D008875:Middle Aged; D011203:Poverty; D011237:Predictive Value of Tests; D015995:Prevalence; D011859:Radiography; D012107:Research Design; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013546:Sweating; D014376:Tuberculosis / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000453:epidemiology*; D015431:Weight Loss; D055815:Young Adult
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