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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Gold standard cholera diagnostics are tarnished by lytic bacteriophage and antibiotics
Journal of Clinical Microbiology, Volume 58, No. 9, Article e00412-20, Year 2020
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Description
A fundamental, clinical, and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity. Cholera was chosen as a model disease to investigate this important question, because cholera outbreaks enable large enrollment, field methods are well established, and the predatory relationship between lytic bacteriophage and the etiologic agent Vibrio cholerae share commonalities across bacterial taxa. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as a function of lytic bacteriophage detection and exposure to the first-line antibiotic azithromycin, detected in stool samples by mass spectrometry. Among diarrheal samples positive by nanoliter quantitative PCR (qPCR) for V. cholerae (n=78/849), the odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by 89% (odds ratio [OR], 0.108; 95% confidence interval [CI], 0.002 to 0.872) and 87% (OR, 0.130; 95% CI, 0.022 to 0.649), respectively, when lytic bacteriophage were detected. The odds that an RDT or qPCR was positive was reduced by more than 99% (OR, 0.00; 95% CI, 0.00 to 0.28) and 89% (OR, 0.11; 95% CI, 0.03 to 0.44), respectively, when azithromycin was detected. Analysis of additional samples from South Sudan found similar phage effects on RDTs; antibiotics were not assayed. Cholera burden estimates may improve by accommodating for the negative effects of lytic bacteriophage and antibiotic exposure on diagnostic positivity. One accommodation is using bacteriophage detection as a proxy for pathogen detection. These findings have relevance for other diagnostic settings where bacterial pathogens are vulnerable to lytic bacteriophage predation. © 2020 Nelson et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC7448619/bin/JCM.00412-20-s0002.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC7448619/bin/JCM.00412-20-sd001.csv
Authors & Co-Authors
Nelson, Eric Jorge
United States, Gainesville
University of Florida
United States, Palo Alto
Stanford University
Grembi, Jessica A.
United States, Palo Alto
Stanford University
Chao, Dennis L.
United States, Bellevue
Institute for Disease Modeling
Andrews, Jason Randolph
United States, Palo Alto
Stanford University
Wamala, Joseph Francis
Switzerland, Geneva
Organisation Mondiale de la Santé
Debes, Amanda Kay
United States, Baltimore
Johns Hopkins University
Sack, David Allen
United States, Baltimore
Johns Hopkins University
Haque, Farhana Islam
Bangladesh, Dhaka
Ministry of Health and Family Welfare
Rahman, M. Mahmudur
Bangladesh, Dhaka
Ministry of Health and Family Welfare
Schoolnik, Gary K.
United States, Palo Alto
Stanford University
Statistics
Citations: 7
Authors: 10
Affiliations: 6
Identifiers
Doi:
10.1128/JCM.00412-20
ISSN:
00951137
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Case-Control Study
Study Approach
Quantitative
Study Locations
South Sudan
Sudan