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Use of oral cholera vaccine as a vaccine probe to determine the burden of culture-negative cholera

Analyses of stool from patients with acute watery diarrhea (AWD) using sensitive molecular diagnostics have challenged whether fecal microbiological cultures have acceptably high sensitivity for cholera diagnosis. If true, these findings imply that current estimates of the global burden of cholera,...

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Autores principales: Im, Justin, Islam, Md. Taufiqul, Ahmmed, Faisal, Kim, Deok Ryun, Chon, Yun, Zaman, K, Khan, Ashraful Islam, Ali, Mohammad, Marks, Florian, Qadri, Firdausi, Clemens, John D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417643/
https://www.ncbi.nlm.nih.gov/pubmed/30870416
http://dx.doi.org/10.1371/journal.pntd.0007179
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author Im, Justin
Islam, Md. Taufiqul
Ahmmed, Faisal
Kim, Deok Ryun
Chon, Yun
Zaman, K
Khan, Ashraful Islam
Ali, Mohammad
Marks, Florian
Qadri, Firdausi
Clemens, John D.
author_facet Im, Justin
Islam, Md. Taufiqul
Ahmmed, Faisal
Kim, Deok Ryun
Chon, Yun
Zaman, K
Khan, Ashraful Islam
Ali, Mohammad
Marks, Florian
Qadri, Firdausi
Clemens, John D.
author_sort Im, Justin
collection PubMed
description Analyses of stool from patients with acute watery diarrhea (AWD) using sensitive molecular diagnostics have challenged whether fecal microbiological cultures have acceptably high sensitivity for cholera diagnosis. If true, these findings imply that current estimates of the global burden of cholera, which rely largely on culture-confirmation, may be underestimates. We conducted a vaccine probe study to evaluate this possibility, assessing whether an effective killed oral cholera vaccine (OCV) tested in a field trial in a cholera-endemic population conferred protection against cholera culture-negative AWD, with the assumption that if cultures are indeed insensitive, OCV protection in such cases should be detectable. We re-analysed the data of a Phase III individually-randomized placebo-controlled efficacy trial of killed OCVs conducted in Matlab, Bangladesh in 1985. We calculated the protective efficacy (PE) of a killed whole cell-only (WC-only) OCV against first-episodes of cholera culture-negative AWD during two years of post-dosing follow-up. In secondary analyses, we evaluated PE against cholera culture-negative AWD by age at vaccination, season of onset, and disease severity. In this trial 50,770 people received at least 2 complete doses of either WC-only OCV or placebo, and 791 first episodes of AWD were reported during the follow-up period, of which 365 were culture-positive for Vibrio cholerae O1. Of the 426 culture-negative AWD episodes, 215 occurred in the WC group and 211 occurred in the placebo group (adjusted PE = -1.7%; 95%CI -23.0 to 13.9%, p = 0.859). No measurable PE of OCV was observed against all or severe cholera culture-negative AWD when measured overall or by age and season subgroups. In this OCV probe study we detected no vaccine protection against AWD episodes for which fecal cultures were negative for Vibrio cholera O1. Results from this setting suggest that fecal cultures from patients with AWD were highly sensitive for cholera episodes that were etiologically attributable to this pathogen. Similar analyses of other OCV randomized controlled trials are recommended to corroborate these findings.
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spelling pubmed-64176432019-04-01 Use of oral cholera vaccine as a vaccine probe to determine the burden of culture-negative cholera Im, Justin Islam, Md. Taufiqul Ahmmed, Faisal Kim, Deok Ryun Chon, Yun Zaman, K Khan, Ashraful Islam Ali, Mohammad Marks, Florian Qadri, Firdausi Clemens, John D. PLoS Negl Trop Dis Research Article Analyses of stool from patients with acute watery diarrhea (AWD) using sensitive molecular diagnostics have challenged whether fecal microbiological cultures have acceptably high sensitivity for cholera diagnosis. If true, these findings imply that current estimates of the global burden of cholera, which rely largely on culture-confirmation, may be underestimates. We conducted a vaccine probe study to evaluate this possibility, assessing whether an effective killed oral cholera vaccine (OCV) tested in a field trial in a cholera-endemic population conferred protection against cholera culture-negative AWD, with the assumption that if cultures are indeed insensitive, OCV protection in such cases should be detectable. We re-analysed the data of a Phase III individually-randomized placebo-controlled efficacy trial of killed OCVs conducted in Matlab, Bangladesh in 1985. We calculated the protective efficacy (PE) of a killed whole cell-only (WC-only) OCV against first-episodes of cholera culture-negative AWD during two years of post-dosing follow-up. In secondary analyses, we evaluated PE against cholera culture-negative AWD by age at vaccination, season of onset, and disease severity. In this trial 50,770 people received at least 2 complete doses of either WC-only OCV or placebo, and 791 first episodes of AWD were reported during the follow-up period, of which 365 were culture-positive for Vibrio cholerae O1. Of the 426 culture-negative AWD episodes, 215 occurred in the WC group and 211 occurred in the placebo group (adjusted PE = -1.7%; 95%CI -23.0 to 13.9%, p = 0.859). No measurable PE of OCV was observed against all or severe cholera culture-negative AWD when measured overall or by age and season subgroups. In this OCV probe study we detected no vaccine protection against AWD episodes for which fecal cultures were negative for Vibrio cholera O1. Results from this setting suggest that fecal cultures from patients with AWD were highly sensitive for cholera episodes that were etiologically attributable to this pathogen. Similar analyses of other OCV randomized controlled trials are recommended to corroborate these findings. Public Library of Science 2019-03-14 /pmc/articles/PMC6417643/ /pubmed/30870416 http://dx.doi.org/10.1371/journal.pntd.0007179 Text en © 2019 Im et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Im, Justin
Islam, Md. Taufiqul
Ahmmed, Faisal
Kim, Deok Ryun
Chon, Yun
Zaman, K
Khan, Ashraful Islam
Ali, Mohammad
Marks, Florian
Qadri, Firdausi
Clemens, John D.
Use of oral cholera vaccine as a vaccine probe to determine the burden of culture-negative cholera
title Use of oral cholera vaccine as a vaccine probe to determine the burden of culture-negative cholera
title_full Use of oral cholera vaccine as a vaccine probe to determine the burden of culture-negative cholera
title_fullStr Use of oral cholera vaccine as a vaccine probe to determine the burden of culture-negative cholera
title_full_unstemmed Use of oral cholera vaccine as a vaccine probe to determine the burden of culture-negative cholera
title_short Use of oral cholera vaccine as a vaccine probe to determine the burden of culture-negative cholera
title_sort use of oral cholera vaccine as a vaccine probe to determine the burden of culture-negative cholera
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417643/
https://www.ncbi.nlm.nih.gov/pubmed/30870416
http://dx.doi.org/10.1371/journal.pntd.0007179
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