Clinical and Epidemiological Aspects of Diphtheria: A Systematic Review and Pooled Analysis.
critical vaccination threshold
diphtheria
outbreak
reproductive number
systematic review
Journal
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213
Informations de publication
Date de publication:
24 06 2020
24 06 2020
Historique:
received:
29
01
2019
accepted:
16
08
2019
pubmed:
20
8
2019
medline:
13
3
2021
entrez:
20
8
2019
Statut:
ppublish
Résumé
Diphtheria, once a major cause of childhood morbidity and mortality, all but disappeared following introduction of diphtheria vaccine. Recent outbreaks highlight the risk diphtheria poses when civil unrest interrupts vaccination and healthcare access. Lack of interest over the last century resulted in knowledge gaps about diphtheria's epidemiology, transmission, and control. We conducted 9 distinct systematic reviews on PubMed and Scopus (March-May 2018). We pooled and analyzed extracted data to fill in these key knowledge gaps. We identified 6934 articles, reviewed 781 full texts, and included 266. From this, we estimate that the median incubation period is 1.4 days. On average, untreated cases are colonized for 18.5 days (95% credible interval [CrI], 17.7-19.4 days), and 95% clear Corynebacterium diphtheriae within 48 days (95% CrI, 46-51 days). Asymptomatic carriers cause 76% (95% confidence interval, 59%-87%) fewer cases over the course of infection than symptomatic cases. The basic reproductive number is 1.7-4.3. Receipt of 3 doses of diphtheria toxoid vaccine is 87% (95% CrI, 68%-97%) effective against symptomatic disease and reduces transmission by 60% (95% CrI, 51%-68%). Vaccinated individuals can become colonized and transmit; consequently, vaccination alone can only interrupt transmission in 28% of outbreak settings, making isolation and antibiotics essential. While antibiotics reduce the duration of infection, they must be paired with diphtheria antitoxin to limit morbidity. Appropriate tools to confront diphtheria exist; however, accurate understanding of the unique characteristics is crucial and lifesaving treatments must be made widely available. This comprehensive update provides clinical and public health guidance for diphtheria-specific preparedness and response.
Sections du résumé
BACKGROUND
Diphtheria, once a major cause of childhood morbidity and mortality, all but disappeared following introduction of diphtheria vaccine. Recent outbreaks highlight the risk diphtheria poses when civil unrest interrupts vaccination and healthcare access. Lack of interest over the last century resulted in knowledge gaps about diphtheria's epidemiology, transmission, and control.
METHODS
We conducted 9 distinct systematic reviews on PubMed and Scopus (March-May 2018). We pooled and analyzed extracted data to fill in these key knowledge gaps.
RESULTS
We identified 6934 articles, reviewed 781 full texts, and included 266. From this, we estimate that the median incubation period is 1.4 days. On average, untreated cases are colonized for 18.5 days (95% credible interval [CrI], 17.7-19.4 days), and 95% clear Corynebacterium diphtheriae within 48 days (95% CrI, 46-51 days). Asymptomatic carriers cause 76% (95% confidence interval, 59%-87%) fewer cases over the course of infection than symptomatic cases. The basic reproductive number is 1.7-4.3. Receipt of 3 doses of diphtheria toxoid vaccine is 87% (95% CrI, 68%-97%) effective against symptomatic disease and reduces transmission by 60% (95% CrI, 51%-68%). Vaccinated individuals can become colonized and transmit; consequently, vaccination alone can only interrupt transmission in 28% of outbreak settings, making isolation and antibiotics essential. While antibiotics reduce the duration of infection, they must be paired with diphtheria antitoxin to limit morbidity.
CONCLUSIONS
Appropriate tools to confront diphtheria exist; however, accurate understanding of the unique characteristics is crucial and lifesaving treatments must be made widely available. This comprehensive update provides clinical and public health guidance for diphtheria-specific preparedness and response.
Identifiants
pubmed: 31425581
pii: 5551532
doi: 10.1093/cid/ciz808
pmc: PMC7312233
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
89-97Subventions
Organisme : NIAID NIH HHS
ID : R01 AI102939
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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