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Volume 29, Number 2—February 2023

Hepatitis E Virus Outbreak among Tigray War Refugees from Ethopia, Sudan

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To the Editor: We read with interest the article by Ahmed et al. on a large hepatitis E virus (HEV) outbreak among refugees from Ethiopia in Sudan, underscoring the challenges in controlling HEV outbreaks (1). As part of the rationale for not using HEV vaccine, the authors state that no data on virus genotype were available from cases and “the success of vaccination is dependent on the HEV genotype.” We believe that current evidence contradicts this assertion.

Evidence to date suggests that all major HEV genotypes that infect humans (genotypes 1–4) show cross-protection with a single serotype. Several pieces of data indicate that the only available and licensed vaccine (Hecolin; Wantai BioPharm,, which contains recombinant partial capsid protein of HEV genotype 1, offers protection against infection with other genotypes. Studies in rhesus macaques have demonstrated protection by this vaccine against infection with genotypes 1 and 4 (2). In a large phase 3 trial of Hecolin, of the 23 persons who had HEV infection (1 in vaccine group and 22 in placebo group), viral genotype was identified in 13 placebo group patients. Of those, 12 were genotype 4 and 1 was genotype 1, providing evidence of protection against genotype 4 infection, a heterologous strain to that in the vaccine (3). Furthermore, in vitro data also support cross-protection across HEV genotypes (4).

A safe and efficacious vaccine is available and has been recommended for use as an outbreak control tool by the World Health Organization Strategic Advisory Group of Experts on Immunization (5), and this recommendation does not refer to virus genotype. Because empirical evidence from in vitro studies, nonhuman primate challenge studies, and a phase 3 clinical trial all point to cross-genotype protection, we believe that the lack of genotyping data during an outbreak should not prevent or delay the use of the HEV vaccine.


Andrew S. AzmanComments to Author , Etienne Gignoux, Robin Nesbitt, John Rumunu, Rakesh Aggarwal, and Iza Ciglenecki
Author affiliations: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA (A.S. Azman); Médecins Sans Frontières, Geneva, Switzerland (A.S. Azman, I. Ciglenecki); Epicentre, Paris, France (E. Gignoux, R. Nesbitt); Ministry of Health South Sudan, Juba, South Sudan (J. Rumunu); Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India (R. Aggarwal)



  1. Ahmed  A, Ali  Y, Siddig  EE, Hamed  J, Mohamed  NS, Khairy  A, et al. Hepatitis E virus outbreak among Tigray War refugees from Ethiopia, Sudan. Emerg Infect Dis. 2022;28:17224. DOIPubMedGoogle Scholar
  2. Li  SW, Zhang  J, Li  YM, Ou  SH, Huang  GY, He  ZQ, et al. A bacterially expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates. Vaccine. 2005;23:2893901. DOIPubMedGoogle Scholar
  3. Zhu  FC, Zhang  J, Zhang  XF, Zhou  C, Wang  ZZ, Huang  SJ, et al. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet. 2010;376:895902. DOIPubMedGoogle Scholar
  4. Gu  Y, Tang  X, Zhang  X, Song  C, Zheng  M, Wang  K, et al. Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody. Cell Res. 2015;25:60420. DOIPubMedGoogle Scholar
  5. WHO. Hepatitis E vaccine: WHO position paper, May 2015—Recommendations. Vaccine. 2016;34:3045. DOIPubMedGoogle Scholar


Cite This Article

DOI: 10.3201/eid2902.221495

Original Publication Date: January 16, 2023

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Table of Contents – Volume 29, Number 2—February 2023

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Please use the form below to submit correspondence to the authors or contact them at the following address:

Andrew S. Azman, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA

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Page created: November 17, 2022
Page updated: January 16, 2023
Page reviewed: January 16, 2023
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.