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The aim of this paper was to assess the transmission potential of …

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

This study estimated the force of infection of swine HEV for three geographic locations in Japan. For the estimation, we incorporated two realistic aspects of swine HEV transmission: (1) no exposure during the suckling stage and (2) time delay of seroconversion after exposure to the virus. As a result, the force of infection was estimated to be approximately 0.03 day-1 implying that the average age at infection is 63 days after birth. According to the estimates, the basic reproduction number, R0, was in the order of 4–5, which is relatively high compared to other diseases [32,41]. To the best of our knowledge, this study is the first to quantify the transmission potential of swine HEV infection. Although the model needs a few rough assumptions, and despite limited precision of the observed data (i.e. seroprevalence data was only collected monthly), our model successfully provides similar estimates of λ for 3 discrete locations. Except for a slight deviation seen in Hokkaido where the samples were taken from numerous sub-regions in the large prefecture, the model adequately explained the basic aspects of the age-specific pattern of HEV seroprevalence in swine. Estimated force of infection was highest in Hokkaido, the northernmost prefecture, while Honshu revealed the lowest estimate. The force of infection depends on various factors influencing transmission (e.g. biological, environmental and demographic factors). In particular, as the disease is transmitted through virus contamination (i.e. fecal-oral route), breeding methods and other determinants affecting exposure are likely to influence the age-specific patterns of prevalence. Whereas the farms in Hokkaido were partly infested with both genotypes III and IV, only genotype III was observed in the other two regions. However, since these two genotypes are immunologically crossreactive each other [5,42], these could not be separately evaluated without detailed information with respect to differences in natural history and immune reaction.

There are two practical implications from our exercise. First, estimation of the force of infection permitted clarification of the average age at infection (being 63 days). Although our model did not allow more detailed age- and time-specificity of the force of infection to be derived due to limited data [37-40], knowing the average age at infection enables clarification of the age-specific incidence of infection (as shown in Figure 3), thereby providing a reasonable assessment of the risk of HEV excretion in slaughtered pigs. According to rigorous inoculation experiments [9,13,43], swine HEV RNA can be detected in the liver, feces, bile and other parts of the body as long as 30 days post-inoculation. In enzootic areas, therefore, pigs should ideally be infected sufficiently far in advance of reaching 150 days of age, so that the probability of virus excretion will be extremely low at 180 days. Although our estimates of the force of infection in Japan imply that the majority of individuals (i.e., more than 95%) are infected before the age of 150 days, it should be noted that any future decline in the force of infection would increase the number of virus-positive pigs at the age of 180 days. Thus, most importantly, it must be remembered that a slight decline in the force of infection could elevate the age at infection and increase the risk of pig-to-human transmission. In addition to consumption of contaminated pork by the general public, the increased risk of infection could also be a particularly risk for veterinarians and boar meat processing workers [44,45]. If the force of infection is naturally reduced on the farm, this could necessitate radical control measures to minimize the number of virus-excreting pigs at the finishing stage and to eliminate the transmission from the farm. Since the population dynamics model can account for more detailed mechanisms of transmission [46-48], further explicit clarification on this point is a subject of our further studies. Although the time required for seroconversion may be slightly underestimated (because of the estimation using intravenous inoculation rather than that through oral routes), this underestimation would only result in slight underestimation of the force of infection, and thus, the above qualitative discussion of the results and their implications is still valid.

Second, the critical coverage of vaccination required for eradication, pc, is obtained from R0, using pc > 1-1/R0 [34]. Although vaccines are currently under development [31], our estimate of R0, ranging from 4.02–5.17, suggests that the HEV transmission on the farm could be prevented if more than 75.1–80.7 % of the pigs were successfully immunized. However, since HEV infection in man is likely to result in asymptomatic or mild disease [3,16,49], and because pig-to-human transmission could be partly prevented by dietary changes of humans (i.e. avoiding consumption of fresh liver), potential future vaccination policies for swine need to take account of cost-benefit analyses and the biological feasibility of elimination. For example, the maintenance of the virus by other primates could prevent the elimination of virus transmission in swine [3,10]. Rather, if it becomes necessary to implement radical control measures, it may be more realistic and less costly to control the transmission within a herd at specific stages; considering that more than four-fifths of infection had happened between the ages of 30 and 90 days, temporal separation of uninfected young pigs from infected herds beginning from the end of suckling stage (e.g. for a certain time period, breed the individuals in a new house) could limit the chance of continued transmission. In this case, tight management of newly-built pig farms (i.e. prevention of contamination from other locations and animals) combined with the possibility of vaccination in the future might be necessary to reduce transmission within the herd.

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