Pneumonia surveillance with culture-independent metatranscriptomics in HIV-positive adults in Uganda: a cross-sectional study.


Journal

The Lancet. Microbe
ISSN: 2666-5247
Titre abrégé: Lancet Microbe
Pays: England
ID NLM: 101769019

Informations de publication

Date de publication:
05 2022
Historique:
received: 11 02 2021
revised: 01 12 2021
accepted: 14 12 2021
entrez: 11 5 2022
pubmed: 12 5 2022
medline: 18 5 2022
Statut: ppublish

Résumé

Pneumonia is a leading cause of death worldwide and is a major health-care challenge in people living with HIV. Despite this, the causes of pneumonia in this population remain poorly understood. We aimed to assess the feasibility of metatranscriptomics for epidemiological surveillance of pneumonia in patients with HIV in Uganda. We performed a retrospective observational study in patients with HIV who were admitted to Mulago Hospital, Kampala, Uganda between Oct 1, 2009, and Dec 31, 2011. Inclusion criteria were age 18 years or older, HIV-positivity, and clinically diagnosed pneumonia. Exclusion criteria were contraindication to bronchoscopy or an existing diagnosis of tuberculosis. Bronchoalveolar lavage fluid was collected within 72 h of admission and a combination of RNA sequencing and Mycobacterium tuberculosis culture plus PCR were performed. The primary outcome was detection of an established or possible respiratory pathogen in the total study population. We consecutively enrolled 217 patients during the study period. A potential microbial cause for pneumonia was identified in 211 (97%) patients. At least one microorganism of established respiratory pathogenicity was identified in 113 (52%) patients, and a microbe of possible pathogenicity was identified in an additional 98 (45%). M tuberculosis was the most commonly identified established pathogen (35 [16%] patients; in whom bacterial or viral co-infections were identified in 13 [37%]). Streptococcus mitis, although not previously reported as a cause of pneumonia in patients with HIV, was the most commonly identified bacterial organism (37 [17%] patients). Haemophilus influenzae was the most commonly identified established bacterial pathogen (20 [9%] patients). Pneumocystis jirovecii was only identified in patients with a CD4 count of less than 200 cells per mL. We show the feasibility of using metatranscriptomics for epidemiologic surveillance of pneumonia by describing the spectrum of respiratory pathogens in adults with HIV in Uganda. Applying these methods to a contemporary cohort could enable broad assessment of changes in pneumonia aetiology following the emergence of SARS-CoV-2. US National Institutes of Health, Chan Zuckerberg Biohub.

Sections du résumé

BACKGROUND
Pneumonia is a leading cause of death worldwide and is a major health-care challenge in people living with HIV. Despite this, the causes of pneumonia in this population remain poorly understood. We aimed to assess the feasibility of metatranscriptomics for epidemiological surveillance of pneumonia in patients with HIV in Uganda.
METHODS
We performed a retrospective observational study in patients with HIV who were admitted to Mulago Hospital, Kampala, Uganda between Oct 1, 2009, and Dec 31, 2011. Inclusion criteria were age 18 years or older, HIV-positivity, and clinically diagnosed pneumonia. Exclusion criteria were contraindication to bronchoscopy or an existing diagnosis of tuberculosis. Bronchoalveolar lavage fluid was collected within 72 h of admission and a combination of RNA sequencing and Mycobacterium tuberculosis culture plus PCR were performed. The primary outcome was detection of an established or possible respiratory pathogen in the total study population.
FINDINGS
We consecutively enrolled 217 patients during the study period. A potential microbial cause for pneumonia was identified in 211 (97%) patients. At least one microorganism of established respiratory pathogenicity was identified in 113 (52%) patients, and a microbe of possible pathogenicity was identified in an additional 98 (45%). M tuberculosis was the most commonly identified established pathogen (35 [16%] patients; in whom bacterial or viral co-infections were identified in 13 [37%]). Streptococcus mitis, although not previously reported as a cause of pneumonia in patients with HIV, was the most commonly identified bacterial organism (37 [17%] patients). Haemophilus influenzae was the most commonly identified established bacterial pathogen (20 [9%] patients). Pneumocystis jirovecii was only identified in patients with a CD4 count of less than 200 cells per mL.
INTERPRETATION
We show the feasibility of using metatranscriptomics for epidemiologic surveillance of pneumonia by describing the spectrum of respiratory pathogens in adults with HIV in Uganda. Applying these methods to a contemporary cohort could enable broad assessment of changes in pneumonia aetiology following the emergence of SARS-CoV-2.
FUNDING
US National Institutes of Health, Chan Zuckerberg Biohub.

Identifiants

pubmed: 35544096
pii: S2666-5247(21)00357-8
doi: 10.1016/S2666-5247(21)00357-8
pii:
doi:

Types de publication

Journal Article Observational Study Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

e357-e365

Subventions

Organisme : NIAID NIH HHS
ID : T32 AI060537
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL098964
Pays : United States
Organisme : NHLBI NIH HHS
ID : K24 HL087713
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL090335
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL143998
Pays : United States

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests LH reports grants from the US National Institutes of Health. SI is employed by Second Genome. SVL reports fees from Siolta Therapeutics, outside of the submitted work. All other authors declare no competing interests.

Auteurs

Natasha Spottiswoode (N)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Division of Infectious Diseases, University of California, San Francisco, San Francisco, CA, USA.

Joshua D Bloomstein (JD)

Department of Medicine, University of California Davis School of Medicine, Sacramento, CA, USA.

Saharai Caldera (S)

Division of Infectious Diseases, University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.

Abdul Sessolo (A)

Infectious Disease Platform, Makerere University, Kampala, Uganda.

Kathryn McCauley (K)

Division of Gastroenterology, University of California, San Francisco, San Francisco, CA, USA.

Patrick Byanyima (P)

Infectious Disease Platform, Makerere University, Kampala, Uganda.

Josephine Zawedde (J)

Infectious Disease Platform, Makerere University, Kampala, Uganda.

Katrina Kalantar (K)

Chan Zuckerberg Initiative, Redwood City, CA, USA.

Sylvia Kaswabuli (S)

Infectious Disease Platform, Makerere University, Kampala, Uganda.

Rachel L Rutishauser (RL)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, USA.

Monica K Lieng (MK)

Department of Medicine, University of California Davis School of Medicine, Sacramento, CA, USA.

J Lucian Davis (JL)

Department of Epidemiology of Microbial Diseases, Yale School of Public Health and Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.

Julia Moore (J)

Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA, USA; Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, San Francisco, CA, USA.

Amanda Jan (A)

Department of Epidemiology of Microbial Diseases, Yale School of Public Health and Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.

Shoko Iwai (S)

Division of Gastroenterology, University of California, San Francisco, San Francisco, CA, USA.

Meera Shenoy (M)

Division of Gastroenterology, University of California, San Francisco, San Francisco, CA, USA.

Ingvar Sanyu (I)

Infectious Disease Platform, Makerere University, Kampala, Uganda.

Joseph L DeRisi (JL)

Department of Biochemistry, University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.

Susan V Lynch (SV)

Division of Gastroenterology, University of California, San Francisco, San Francisco, CA, USA.

William Worodria (W)

Infectious Disease Platform, Makerere University, Kampala, Uganda.

Laurence Huang (L)

Division of Pulmonary and Critical Care Medicine, University of California, San Francisco, San Francisco, CA, USA; Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, San Francisco, CA, USA.

Charles R Langelier (CR)

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Division of Infectious Diseases, University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA. Electronic address: chaz.langelier@ucsf.edu.

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Classifications MeSH