F A S Gualberto1, M G Gonçalves2, L O Fukasawa2, A M Ramos Dos Santos3, C T Sacchi2, L H Harrison4, D R Boulware5, J E Vidal6. 1. Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Departamento de Infectologia, Instituto de Infectologia Emílio Ribas, São Paulo, Centro de Imunologia, Instituto Adolfo Lutz, São Paulo, São Paulo, Brazil. 2. Centro de Imunologia, Instituto Adolfo Lutz, São Paulo, São Paulo, Brazil. 3. Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Departamento de Infectologia, Instituto de Infectologia Emílio Ribas, São Paulo. 4. Infectious Diseases Epidemiology Research Unit, University of Pittsburgh, Pittsburgh, Pennsylvania. 5. Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA. 6. Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Departamento de Neurologia, Instituto de Infectologia Emília Ribas, São Paulo, Laboratório de Investigação Médica 49, Instituto de Medicina Tropical, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil.
Abstract
SETTING: Timely diagnosis of tuberculous meningitis (TBM) in patients with human immunodeficiency virus (HIV) infection remains a challenge. Despite the current scale-up of the Xpert® MTB/RIF assay, other molecular diagnostic tools are necessary, particularly in referral centres in low- and middle-income countries without Xpert testing. OBJECTIVE: To determine the diagnostic performance of nested real-time polymerase chain reaction (nRT-PCR) in HIV-infected TBM patients categorised according to standardised clinical case definitions. DESIGN: Based on clinical, laboratory and imaging data, HIV-infected patients with suspected TBM were prospectively categorised as 'definite TBM', 'probable TBM', 'possible TBM' or 'not TBM'. We evaluated nRT-PCR sensitivity and specificity in diagnosing TBM among definite TBM cases, and among definite + probable TBM cases. RESULTS: Ninety-two participants were enrolled in the study. nRT-PCR sensitivity for definite TBM (n = 8) was 100% (95%CI 67-100) and 86% (95%CI 60-96) for both definite and probable TBM (n = 6). Assuming that 'not TBM' patients (n = 74) were true-negatives, nRT-PCR specificity was 100% (95%CI 95-100). The possible TBM group (n = 4) had no nRT-PCR positives. CONCLUSIONS: The nRT-PCR is a useful rule-in test for HIV-infected patients with TBM according to international consensus case definitions. As nRT-PCR cannot exclude TBM, studies comparing and combining nRT-PCR with other assays are necessary for a rule-out test.
SETTING: Timely diagnosis of tuberculous meningitis (TBM) in patients with human immunodeficiency virus (HIV) infection remains a challenge. Despite the current scale-up of the Xpert® MTB/RIF assay, other molecular diagnostic tools are necessary, particularly in referral centres in low- and middle-income countries without Xpert testing. OBJECTIVE: To determine the diagnostic performance of nested real-time polymerase chain reaction (nRT-PCR) in HIV-infected TBMpatients categorised according to standardised clinical case definitions. DESIGN: Based on clinical, laboratory and imaging data, HIV-infectedpatients with suspected TBM were prospectively categorised as 'definite TBM', 'probable TBM', 'possible TBM' or 'not TBM'. We evaluated nRT-PCR sensitivity and specificity in diagnosing TBM among definite TBM cases, and among definite + probable TBM cases. RESULTS: Ninety-two participants were enrolled in the study. nRT-PCR sensitivity for definite TBM (n = 8) was 100% (95%CI 67-100) and 86% (95%CI 60-96) for both definite and probable TBM (n = 6). Assuming that 'not TBM' patients (n = 74) were true-negatives, nRT-PCR specificity was 100% (95%CI 95-100). The possible TBM group (n = 4) had no nRT-PCR positives. CONCLUSIONS: The nRT-PCR is a useful rule-in test for HIV-infectedpatients with TBM according to international consensus case definitions. As nRT-PCR cannot exclude TBM, studies comparing and combining nRT-PCR with other assays are necessary for a rule-out test.
Authors: Adrian V Hernandez; Laryssa de Laurentis; Isadora Souza; Marcelo Pessanha; Priyaleela Thota; Yuani M Roman; Joshuan Barboza-Meca; David R Boulware; Jose E Vidal Journal: Trop Med Int Health Date: 2020-11-30 Impact factor: 2.622