Truelove SA*, Keegan LT*, Moss WJ, Chaisson, LH, Macher E, Azman AS, Lessler J. Clinical and epidemiological aspects of diphtheria: A systematic review and pool analysis. Clinical Infectious Diseases. 2019. https://doi.org/10.1093/cid/ciz808
* equal contribution
Background. Diphtheria, once a major cause of childhood morbidity and mortality, all but disappeared following the vaccine introduction. 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 nine distinct systematic reviews on PubMed and Scopus (March to May 2018). We pooled and analyzed extracted data to fill in these key knowledge gaps.
Results. We identified 6,934 articles, reviewed 781 full texts, and included 266. From this, we estimate the median incubation period is 1.4 days. On average, untreated cases are colonized for 18.5 days (95% CI, 17.7-19.4), and 95% clear Corynebacterium diphtheriae within 48 days (95% CI, 46-51). Asymptomatic carriers cause 76% (95% CI, 59-87%) fewer cases over the course of infection than symptomatic cases. The basic reproductive number is 1.7-4.3. Three doses of diphtheria toxoid vaccine are 87% (95% CI, 68-97%) effective against symptomatic disease and reduce transmission by 60% (95% CI, 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.
Conclusion. 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.
This repository contains all of the data and code required to perform the analyses from the manuscript. See Run_Diphtheria_Analyses.Rmd for which scripts are required for each specific analysis.