Jill K Gersh1, Ruanne V Barnabas1,2,3, Daniel Matemo4,5, John Kinuthia2,4, Zachary Feldman6, Sylvia M Lacourse1,2, Jerphason Mecha4, Alex J Warr7, Maureen Kamene8, David J Horne9,10. 1. Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, USA. 2. Department of Global Health, University of Washington, 325 9th Ave, Box 359762, Seattle, WA, 98102, USA. 3. Department of Epidemiology, University of Washington, Seattle, WA, USA. 4. Department of Obstetrics and Gynaecology, Kenyatta National Hospital, Nairobi, Kenya. 5. School of Public Health and Community Development Maseno University, Kisumu, Kenya. 6. Albers School of Business and Economics, Seattle University, Seattle, WA, USA. 7. Department of Pediatrics, Department of Medicine, Baylor College of Medicine, Houston, TX, USA. 8. National Tuberculosis, Leprosy, and Lung Disease Program, Nairobi, Kenya. 9. Department of Global Health, University of Washington, 325 9th Ave, Box 359762, Seattle, WA, 98102, USA. dhorne@uw.edu. 10. Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Harborview Medical Center, Seattle, WA, USA. dhorne@uw.edu.
Abstract
BACKGROUND: People living with HIV (PLHIV) who reside in high tuberculosis burden settings remain at risk for tuberculosis disease despite treatment with anti-retroviral therapy and isoniazid preventive therapy (IPT). The performance of the World Health Organization (WHO) symptom screen for tuberculosis in PLHIV receiving anti-retroviral therapy is sub-optimal and alternative screening strategies are needed. METHODS: We enrolled HIV-positive adults into a prospective study in western Kenya. Individuals who were IPT-naïve or had completed IPT > 6 months prior to enrollment were eligible. We evaluated tuberculosis prevalence overall and by IPT status. We assessed the accuracy of the WHO symptom screen, GeneXpert MTB/RIF (Xpert), and candidate biomarkers including C-reactive protein (CRP), hemoglobin, erythrocyte sedimentation rate (ESR), and monocyte-to-lymphocyte ratio for identifying pulmonary tuberculosis. Some participants were evaluated at 6 months post-enrollment for tuberculosis. RESULTS: The study included 383 PLHIV, of whom > 99% were on antiretrovirals and 88% had received IPT, completed a median of 1.1 years (IQR 0.8-1.55) prior to enrollment. The prevalence of pulmonary tuberculosis at enrollment was 1.3% (n = 5, 95% CI 0.4-3.0%): 4.3% (0.5-14.5%) among IPT-naïve and 0.9% (0.2-2.6%) among IPT-treated participants. The sensitivity of the WHO symptom screen was 0% (0-52%) and specificity 87% (83-90%). Xpert and candidate biomarkers had poor to moderate sensitivity; the most accurate biomarker was CRP ≥ 3.3 mg/L (sensitivity 80% (28-100) and specificity 72% (67-77)). Six months after enrollment, the incidence rate of pulmonary tuberculosis following IPT completion was 0.84 per 100 person-years (95% CI, 0.31-2.23). CONCLUSIONS: In Kenyan PLHIV treated with IPT, tuberculosis prevalence was low at a median of 1.4 years after IPT completion. WHO symptoms screening, Xpert, and candidate biomarkers were insensitive for identifying pulmonary tuberculosis in antiretroviral-treated PLHIV.
BACKGROUND:People living with HIV (PLHIV) who reside in high tuberculosis burden settings remain at risk for tuberculosis disease despite treatment with anti-retroviral therapy and isoniazid preventive therapy (IPT). The performance of the World Health Organization (WHO) symptom screen for tuberculosis in PLHIV receiving anti-retroviral therapy is sub-optimal and alternative screening strategies are needed. METHODS: We enrolled HIV-positive adults into a prospective study in western Kenya. Individuals who were IPT-naïve or had completed IPT > 6 months prior to enrollment were eligible. We evaluated tuberculosis prevalence overall and by IPT status. We assessed the accuracy of the WHO symptom screen, GeneXpert MTB/RIF (Xpert), and candidate biomarkers including C-reactive protein (CRP), hemoglobin, erythrocyte sedimentation rate (ESR), and monocyte-to-lymphocyte ratio for identifying pulmonary tuberculosis. Some participants were evaluated at 6 months post-enrollment for tuberculosis. RESULTS: The study included 383 PLHIV, of whom > 99% were on antiretrovirals and 88% had received IPT, completed a median of 1.1 years (IQR 0.8-1.55) prior to enrollment. The prevalence of pulmonary tuberculosis at enrollment was 1.3% (n = 5, 95% CI 0.4-3.0%): 4.3% (0.5-14.5%) among IPT-naïve and 0.9% (0.2-2.6%) among IPT-treated participants. The sensitivity of the WHO symptom screen was 0% (0-52%) and specificity 87% (83-90%). Xpert and candidate biomarkers had poor to moderate sensitivity; the most accurate biomarker was CRP ≥ 3.3 mg/L (sensitivity 80% (28-100) and specificity 72% (67-77)). Six months after enrollment, the incidence rate of pulmonary tuberculosis following IPT completion was 0.84 per 100 person-years (95% CI, 0.31-2.23). CONCLUSIONS: In Kenyan PLHIV treated with IPT, tuberculosis prevalence was low at a median of 1.4 years after IPT completion. WHO symptoms screening, Xpert, and candidate biomarkers were insensitive for identifying pulmonary tuberculosis in antiretroviral-treated PLHIV.
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