Reactive and pre-emptive vaccination strategies to control hepatitis E infection in emergency and refugee settings: a modelling study
Ben S Cooper1, Lisa White1, *Ruby Siddiqui2
1Mahidol Oxford Tropical Medicine Research Unit , Bangkok, Thailand;2Médecins Sans Frontières (MSF), London, UK
*
Introduction
Hepatitis E virus (HEV) is an important cause of morbidity and mortality in emergency and refugee camp settings. Symptomatic infection is associated with case fatality rates of ~20% in pregnant women. However, its epidemiology is poorly understood and the potential impact of immunisation in outbreak settings is uncertain. We aimed to estimate key epidemiological parameters for HEV and evaluate the potential impact (mortality reduction) of reactive and pre-emptive vaccination strategies.
Methods
Data came from epidemics in 2007-2009 from three internally displaced persons camps in the district of Kitgum, Uganda (estimated populations 16,689, 10,442, and 10,555). Jaundice cases were recorded in facility-based passive surveillance systems and HEV confirmed to be the outbreak cause. We analysed data by fitting transmission dynamic models and used fitted models to assess the expected impact of different vaccination policies. In our baseline model, individuals were assumed to be in one of four states: susceptible to infection; latently-infected but not yet infectious; infectious; and recovered and immune. The rate at which susceptibles became infected was assumed to scale linearly with the number currently infectious. Model fitting was performed in a Bayesian framework, making use of information from previous studies. We also performed multiple sensitivity analyses using models with different assumptions consistent with prior data.
Ethics
This research fulfilled the exemption criteria set by the MSF ERB for a posteriori analyses of routinely collected clinical data and thus did not require MSF ERB review. It was conducted with permission from Sidney Wong, Operational Centre Amsterdam, MSF.
Results
Under baseline assumptions, we estimated the basic reproduction number of HEV to range from 3.9 (95% credible interval [CrI]: 2.8, 5.4) to 8.9 (5.4, 14.2). Mean latent and infectious periods were estimated to be 34 days (28, 39) and 40 days (23, 71) respectively. If initiated after 50 reported cases, reactive two-dose vaccination of persons 16-65 years, excluding pregnant women (for whom the vaccine is not currently licensed), led to mean camp-specific reductions in mortality of 10 to 29%. Pre-emptive vaccination with two doses reduced mortality by 35 to 65%. Both strategies were far more effective if coverage was extended to groups for whom the vaccine is not currently licensed, particularly pregnant women. For example, two dose pre-emptive vaccination, if extended to include pregnant women, led to mean reductions in mortality of 66 to 82%. Broadly similar results were found in sensitivity analyses.
Conclusion
There is high potential for transmission of HEV in refugee camp settings. Substantial reductions in mortality can be achieved through vaccination, even if vaccination is only reactive, particularly if the vaccine’s safety and effectiveness can be established in pregnant women.
Conflicts of interest
None declared.