Global Epidemiology of Diphtheria, 2000–2017

Kristie E.N. Clarke; Adam MacNeil; Stephen Hadler; Colleen Scott; Tejpratap S.P. Tiwari; Thomas Cherian

Disclosures

Emerging Infectious Diseases. 2019;25(10):1834-1842. 

In This Article

Abstract and Introduction

Abstract

In 2017, a total of 8,819 cases of diphtheria were reported worldwide, the most since 2004. However, recent diphtheria epidemiology has not been well described. We analyzed incidence data and data from the literature to describe diphtheria epidemiology. World Health Organization surveillance data were 81% complete; completeness varied by region, indicating underreporting. As national diphtheria–tetanus–pertussis (DTP) 3 coverage increased, the proportion of case-patients <15 years of age decreased, indicating increased protection of young children. In countries with higher case counts, 66% of case-patients were unvaccinated and 63% were <15 years of age. In countries with sporadic cases, 32% of case-patients were unvaccinated and 66% were ≥15 years of age, consistent with waning vaccine immunity. Global DTP3 coverage is suboptimal. Attaining high DTP3 coverage and implementing recommended booster doses are necessary to decrease diphtheria incidence. Collection and use of data on subnational and booster dose coverage, enhanced laboratory capacity, and case-based surveillance would improve data quality.

Introduction

Diphtheria was a leading cause of childhood death in the prevaccine era.[1] Incidence in industrialized countries decreased rapidly with diphtheria–tetanus–pertussis (DTP) vaccine introduction after World War II. Incidence in less developed countries also decreased after the launch of the World Health Organization (WHO) Expanded Programme on Immunization in 1974,[2] which recommended that all infants receive a 3-dose series of DTP vaccine by 6 months of age. A spike in incidence in the newly independent states of the former Soviet Union occurred in the 1990s (Figure 1), resulting in >157,000 cases and 5,000 deaths.[1] This spike demonstrated the potential for severe outbreaks of diphtheria in communities that have a large population of nonimmune adults and poor vaccination coverage for children.

Figure 1.

Cases of diphtheria as reported to the World Health Organization and the United Nations Children's Fund, through the Joint Reporting Form, worldwide, 1980−2017.

Although several comprehensive reviews were published after that outbreak peaked,[3–5] only sporadic documentation of diphtheria outbreaks has been published since, and no examination of global epidemiologic trends has been published. During 2016–2019, diphtheria outbreaks were reported in multiple countries, including Bangladesh, Yemen, and Venezuela. Several outbreaks were among vulnerable populations or in areas of social disruption and conflict. Authors in some low- and middle-income countries have reported a resurgence of the disease or a shift to older populations.[6–8] However, the quality of reported surveillance data varies; 26 of 130 responding countries report no diphtheria surveillance system, and only 55 report case-based surveillance with laboratory confirmation.[9] In this context, a review of recent epidemiologic trends is needed to better characterize recent outbreaks.

Given a previous lack of global guidance on diphtheria-containing booster doses after the 3-dose primary series, a wide variety of schedules had been adopted by different countries as of 2018.[10–12] Twenty-four percent of countries used the 3-dose series alone, and other countries offered 1–3 booster doses on varying schedules; 24% of countries also included ≥1 adult booster doses, defined as a dose recommended at or after 18 of years of age (Figure 2). Although there are no global estimates of coverage for booster doses, available data suggest coverage is lower than that for the primary series in many countries.[13]

Figure 2.

Percentage (number) of countries reporting each diphtheria vaccination schedule, 2018. The number after the plus sign indicates the number of booster doses on the national schedule after the 3-dose primary series and before the age of 18 years.

In August 2017, WHO released revised recommendations for diphtheria vaccination.[14] In addition to the 3-dose primary series in infancy, new recommendations include 3 diphtheria toxoid–containing booster doses given at 12–23 months of age, 4–7 years of age, and 9–15 years of age. These recommendations, which harmonize with the updated recommendations for tetanus boosters released in February 2017,[15] emphasize the need for a life course vaccination approach and present new opportunities for synergies with other vaccines and healthcare activities, such as measles second dose, preventive care at school entry, and human papillomavirus vaccination. In addition, it is now recommended that the combined tetanus toxoid and diphtheria toxoid vaccine be used during pregnancy and when tetanus prophylaxis is required because of injury, rather than using tetanus toxoid alone. The objective of this study was to review the epidemiology of diphtheria since 2000, including global aggregate surveillance data, vaccination coverage data, and available data regarding the age and vaccination status of infected persons.

Preliminary results from this study were presented at the meeting of the Strategic Advisory Group of Experts on Immunization, Geneva, Switzerland, April 25–27, 2017.

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