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Unmasking the hidden tuberculosis mortality burden in a large postmortem study in Maputo Central Hospital, Mozambique

Alberto L. Garcia-Basteiro, Juan Carlos Hurtado, Paola Castillo, Fabiola Fernandes, Mireia Navarro, Lucilia Lovane, Isaac Casas, Llorenç Quintó, Dercio Jordao, Mamudo R. Ismail, Cesaltina Lorenzoni, Carla Carrilho, Ariadna Sanz, Natalia Rakislova, Aurea Mira, Miriam J. Alvarez-Martínez, Anelsio Cossa, Frank Cobelens, Inácio Mandomando, Jordi Vila, Quique Bassat, Clara Menendez, Jaume Ordi, Miguel J. Martínez
European Respiratory Journal 2019; DOI: 10.1183/13993003.00312-2019
Alberto L. Garcia-Basteiro
1Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique
2ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
3Amsterdam Institute for Global Health and Development, Amsterdam University Medical Centers, Amsterdam, The Netherlands
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Juan Carlos Hurtado
2ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
4Department of Microbiology, Hospital Clinic, Universitat de Barcelona, Spain
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  • ORCID record for Juan Carlos Hurtado
Paola Castillo
2ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
5Department of Pathology, Hospital Clinic, Universitat de Barcelona, Spain
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Fabiola Fernandes
6Department of Pathology, Faculty of Medicine/Eduardo Mondlane University and Maputo Central Hospital, Maputo, Mozambique
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Mireia Navarro
4Department of Microbiology, Hospital Clinic, Universitat de Barcelona, Spain
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Lucilia Lovane
4Department of Microbiology, Hospital Clinic, Universitat de Barcelona, Spain
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Isaac Casas
4Department of Microbiology, Hospital Clinic, Universitat de Barcelona, Spain
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Llorenç Quintó
1Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique
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Dercio Jordao
6Department of Pathology, Faculty of Medicine/Eduardo Mondlane University and Maputo Central Hospital, Maputo, Mozambique
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Mamudo R. Ismail
6Department of Pathology, Faculty of Medicine/Eduardo Mondlane University and Maputo Central Hospital, Maputo, Mozambique
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Cesaltina Lorenzoni
6Department of Pathology, Faculty of Medicine/Eduardo Mondlane University and Maputo Central Hospital, Maputo, Mozambique
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Carla Carrilho
6Department of Pathology, Faculty of Medicine/Eduardo Mondlane University and Maputo Central Hospital, Maputo, Mozambique
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Ariadna Sanz
2ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
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Natalia Rakislova
5Department of Pathology, Hospital Clinic, Universitat de Barcelona, Spain
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Aurea Mira
7Biomedical Diagnostic Centre (CDB), Hospital Clínic, University of Barcelona, Barcelona, Spain
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Miriam J. Alvarez-Martínez
2ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
4Department of Microbiology, Hospital Clinic, Universitat de Barcelona, Spain
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Anelsio Cossa
1Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique
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Frank Cobelens
3Amsterdam Institute for Global Health and Development, Amsterdam University Medical Centers, Amsterdam, The Netherlands
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Inácio Mandomando
1Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique
7Biomedical Diagnostic Centre (CDB), Hospital Clínic, University of Barcelona, Barcelona, Spain
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Jordi Vila
2ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
4Department of Microbiology, Hospital Clinic, Universitat de Barcelona, Spain
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Quique Bassat
1Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique
2ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
9ICREA, Catalan Institution for Research and Advanced Studies, Barcelona, Spain
10Pediatric Infectious Diseases Unit, Pediatrics Department, Hospital Sant Joan de Déu (University of Barcelona), Barcelona, Spain
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Clara Menendez
1Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique
2ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
11Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
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Jaume Ordi
2ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
5Department of Pathology, Hospital Clinic, Universitat de Barcelona, Spain
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Miguel J. Martínez
2ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, Spain
4Department of Microbiology, Hospital Clinic, Universitat de Barcelona, Spain
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  • For correspondence: myoldi@clinic.ub.es
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Abstract

Sensitive tools are needed to accurately establish the diagnosis of tuberculosis (TB) at death, especially in low-income countries. The objective of this study was to evaluate the burden of TB in a series of patients who died in a tertiary referral hospital in sub-Saharan Africa using an in-house real time PCR (TB-PCR) and the Xpert MTB/RIF Ultra (Xpert Ultra) assay.

Complete diagnostic autopsies were performed in a series of 223 deaths (56.5% being HIV-positive), including 54 children, 57 maternal deaths and 112 other adults occurring at the Maputo Central Hospital, Mozambique. TB-PCR was performed in all lung, cerebrospinal fluid and central nervous system samples in HIV-positive patients. All samples positive for TB-PCR or showing histological findings suggestive of TB were analysed with the Xpert Ultra assay.

TB was identified as the cause of death in 31 patients: 3/54 (6%) children, 5/57 (9%) maternal deaths and 23/112 (21%) other adults. The sensitivity of the main clinical diagnosis to detect TB as the cause of death was 19.4% (95% CI: 7.5–37.5) and the specificity was 97.4% (94.0–99.1) compared to autopsy findings. Concomitant TB (TB disease in a patient dying of other causes) was found in 31 additional cases. Xpert Ultra helped to identify 15 cases of concomitant TB. In 18 patients, M. tuberculosis DNA was identified by TB-PCR and Xpert Ultra in the absence of histological TB lesions. Overall, 62 cases (27.8%) had TB disease at death and 80 (35.9%) had TB findings.

The use of highly sensitive, easy to perform molecular tests in complete diagnostic autopsies may contribute to identifying TB cases at death that would have otherwise been missed. Routine use of these tools in certain diagnostic algorithms for hospitalised patients needs to be considered. Clinical diagnosis showed poor sensitivity for the diagnosis of TB at death.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Garcia-Basteiro has nothing to disclose.

Conflict of interest: Dr. Hurtado has nothing to disclose.

Conflict of interest: Dr. Castillo has nothing to disclose.

Conflict of interest: Dr. Fernandes has nothing to disclose.

Conflict of interest: Dr. Navarro has nothing to disclose.

Conflict of interest: Dr. Lovane has nothing to disclose.

Conflict of interest: Dr. Casas has nothing to disclose.

Conflict of interest: Dr. Quinto has nothing to disclose.

Conflict of interest: Dr. Jordao has nothing to disclose.

Conflict of interest: Dr. Ismail has nothing to disclose.

Conflict of interest: Dr. Lorenzoni has nothing to disclose.

Conflict of interest: Dr. Carrilho has nothing to disclose.

Conflict of interest: Dr. Sanz has nothing to disclose.

Conflict of interest: Dr. Rakislova has nothing to disclose.

Conflict of interest: Dr. Mira has nothing to disclose.

Conflict of interest: Dr. Alvarez-Martinez has nothing to disclose.

Conflict of interest: Dr. Cossa has nothing to disclose.

Conflict of interest: Dr. Cobelens has nothing to disclose.

Conflict of interest: Dr. Mandomando has nothing to disclose.

Conflict of interest: Dr. Vila has nothing to disclose.

Conflict of interest: Dr. Bassat has nothing to disclose.

Conflict of interest: Dr. Menendez has nothing to disclose.

Conflict of interest: Dr. Ordi has nothing to disclose.

Conflict of interest: Dr. Martinez has nothing to disclose.

This is a PDF-only article. Please click on the PDF link above to read it.

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Unmasking the hidden tuberculosis mortality burden in a large postmortem study in Maputo Central Hospital, Mozambique
Alberto L. Garcia-Basteiro, Juan Carlos Hurtado, Paola Castillo, Fabiola Fernandes, Mireia Navarro, Lucilia Lovane, Isaac Casas, Llorenç Quintó, Dercio Jordao, Mamudo R. Ismail, Cesaltina Lorenzoni, Carla Carrilho, Ariadna Sanz, Natalia Rakislova, Aurea Mira, Miriam J. Alvarez-Martínez, Anelsio Cossa, Frank Cobelens, Inácio Mandomando, Jordi Vila, Quique Bassat, Clara Menendez, Jaume Ordi, Miguel J. Martínez
European Respiratory Journal Jan 2019, 1900312; DOI: 10.1183/13993003.00312-2019

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Unmasking the hidden tuberculosis mortality burden in a large postmortem study in Maputo Central Hospital, Mozambique
Alberto L. Garcia-Basteiro, Juan Carlos Hurtado, Paola Castillo, Fabiola Fernandes, Mireia Navarro, Lucilia Lovane, Isaac Casas, Llorenç Quintó, Dercio Jordao, Mamudo R. Ismail, Cesaltina Lorenzoni, Carla Carrilho, Ariadna Sanz, Natalia Rakislova, Aurea Mira, Miriam J. Alvarez-Martínez, Anelsio Cossa, Frank Cobelens, Inácio Mandomando, Jordi Vila, Quique Bassat, Clara Menendez, Jaume Ordi, Miguel J. Martínez
European Respiratory Journal Jan 2019, 1900312; DOI: 10.1183/13993003.00312-2019
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