Transmission dynamics of hepatitis E among swine: potential impact upon human infection

Abstract

Background: Hepatitis E virus (HEV) infection is a zoonosis for which pigs play a role as a reservoir. In Japan, the infection has been enzootic in swine. Clarifying the detailed mechanisms of transmission within farms is required in order to facilitate an understanding of the age-specific patterns of infection, especially just prior to slaughter.

Results: Here we reanalyze a large-scale seroprevalence survey dataset from Japanese pig farms to estimate the force of infection. The forces of infection of swine HEV were estimated to be 3.45 (95% confidence interval: 3.17, 3.75), 2.68 (2.28, 3.14) and 3.11 (2.76, 3.50) [x10-2 per day] in Hokkaido, Honshu and Kyushu, respectively. The estimates with our model assumptions indicated that the average ages at infection ranged from 59.0-67.3 days and that the basic reproduction number, R0, was in the order of 4.02-5.17. Sensitivity analyses of age-specific incidence at different forces of infection revealed that a decline in the force of infection would elevate the age at infection and could increase the number of virus-excreting pigs at the age of 180 days.

Conclusion: Although our estimates imply that more than 95% of pigs are infected before the age of 150 days, the model shows that a decline in the force of infection could increase the risk of pig-to-human transmission. If the force of infection started to decline, it might be necessary to implement radical countermeasures (e.g. separation of uninfected pigs from infected herds beginning from the end of the suckling stage) to minimize the number of virus-positive pigs at the finishing stage.

Figure 1

Observed and predicted time required for seroconversion of anti-HEV antibody. Logit model (line) was applied to the observed cumulative distribution of the time required for seroconversion (dot), which revealed a sigmoid pattern. Data source: ref. [9].

Figure 2

Observed and predicted age-specific seroprevalence against swine hepatitis E virus in Japan. Observed (gray bar) and predicted (black) seroprevalence are compared. Three discrete geographic areas, Hokkaido (A), Honshu (B) and Kyushu (C), are modeled separately. Data source: ref. [24].

Figure 3

Cumulative frequency of infection and age-specific incidence at different forces of infection. A. Cumulative frequencies of HEV infection and B. age-specific incidence elicited by different forces of infection are compared. Assumed values for the forces of infection were 0.01 (thick black), 0.03 (thin black) and 0.05 (thick gray) days^-1. See eqs. 6 and 7 for details of the model.

Figure 4

Estimation of the force of infection of hepatitis E virus in Japan. A. The map of three geographic locations in Japan (drawn by the authors). B. Compartment of the catalytic model. Susceptibles at age a, S(a), are infected at a rate λ and then enter into the compartment, infected, I(a). C. Schematic illustration of the time delay to seroconvert. If the time of seroconversion t₀ and possible time of exposure t_k are given, probability of exposure at time t_k can be extracted by g(t₀-t_k), where g(t) is the probability density of the time required for seroconversion at t days after infection. See eqs. 9 and 10 for statistical details.