The clinical signs of PRRSV are reproductive loss in sows including return to oestrus, abortion, premature farrowing, mummified foetuses and stillbirths [3,4]. PRRSV causes high pre-weaning mortality in piglets infected in utero [5] and immunosuppression and consequent increase in susceptibility to other infectious diseases, particularly respiratory diseases in pigs infected post-weaning [6]. The clinical disease caused by PRRSV is highly variable between farms. For example, whilst some seropositive herds have fairly consistent rates of respiratory disease [7,8], others have periodic outbreaks of reproductive disease in breeding sows [9] suggesting that the virus does not behave consistently between farms. There has also been a report of natural fadeout of PRRSV on a farm [10] and some reports of active elimination of PRRSV from individual herds [11,9,13].

The role of fadeout and persistence in determining viral transmission dynamics has been recognised for some time, especially in the context of measles and other childhood infections [14,15]. Periodic outbreaks of measles (and therefore episodes of fadeout) have been observed in small communities [14], with low rate of supply of susceptible individuals (births) and low rates of virus introduction [15]. Persistence of a virus in a host population is critically determined by the availability (proportion) of susceptibles in the population, which is determined by, inter alia, transmissibility of the virus, infectious period and existence of alternative hosts or environment contamination [16-18]. Thus, for PRRSV, the observed variable clinical signs and natural fadeout might occur because of variability in virus transmission within and between farms, different strains of virus, and/or because of transmission dynamic heterogeneity that results when most of the herd becomes immune.

Anti-PRRSV antibodies (detectable by ELISA) arise approximately 9 – 13 days after infection [19] and decay over time [19,12], persisting for up to 28 months [12]. Most pigs clear virus within 3–4 months of exposure [20], so most PRRSV antibody positive pigs are virus negative and consequently seropositivity is an indicator of past infection or vaccination. Whereas seropositivity of adult pigs might have been acquired many months previously in a herd in which the virus has become absent, seropositivity of young stock born on a farm indicates virus presence on that farm.

Vaccinated herds had a slightly higher seropositivity in adults and a similar seropositivity to 14 week old pigs in unvaccinated seropositive herds (Figure (Figure1).1). Both vaccinated and unvaccinated positive herds had a significantly higher proportion of seropositive adults than herds with no seropositive young stock.

There were sixteen positive herds that had seronegative young stock (Figures (Figures1,1, ,22 and and3).3). A herd with an average of 3270 rearing pigs would have approximately 136 pigs of each week of age from 1–24. The total number of eight and 14 week old pigs would therefore constitute 272 of the 3270 rearing pigs. A sample of 20 pigs from these age groups would be sufficient to detect a minimum seroprevalence of 22% with 95% confidence, given the sensitivity and specificity of the ELISA.

For the sixteen positive herds that had seronegative young stock, different serological patterns were observed according to whether herds purchased gilts (10 herds – Figure Figure2)2) or only used homebred replacements (6 herds – Figure Figure3).3). For herds that used homebred replacements, older sows were more likely to be seropositive compared with younger sows (Figure (Figure3).3). Two out of ten herds that purchased gilts also had this pattern (Figure 2a, 2f) but for the majority of herds the seroprevalence was higher in younger sows on the farm (those purchased most recently) (Figure 2b–2e, 2g–2j) These individual farm age-seroprevalence curves demonstrate the between herd variability in exposure of pigs to PRRSV. There were no seropositive herds that had positive young stock and negative adults, nor were there more seropositive 8 week old pigs compared to 14 week old pigs in any herds.

For 33 seronegative herds for which there were veterinarian responses, 26 reported never having seen PRRS on the unit and four stated that the disease had been seen, three of which had been confirmed positive by laboratory diagnosis. All veterinarians of the 27 vaccinated herds stated that PRRS had been seen on the unit in the past and 24 reported that PRRSV was still present. Of 25 seropositive herds with seropositive young stock, 21 veterinarians reported that they had seen PRRS in the past and 12 reported clinical signs since 2000. In addition, of sixteen seropositive herds that had negative young stock, seven attending veterinarians had seen PRRS on these farms in the past and five reported clinical signs since 2002.

In the binomial logistic regression model (Model 1, Table 3), herds were more likely to be seronegative for PRRSV antibodies if there were < 250 sows on the unit (OR = 3.86, 95% CI 1.46, 10.19) and if the nearest pig unit was situated more than 2 miles from the index herd (OR = 3.42, 95% CI 1.29, 9.12). A herd size of < 250 sows was correlated with the unit being a nucleus or multiplier unit rather than a commercial unit. However, there were no other significant differences between commercial and nucleus or multiplier herds; therefore, the number of sows was included in the model. The nearest unit > 2 miles away was correlated with the nearest unit not being a commercial unit (it was a nucleus, multiplier unit, hobby farm or an isolation unit).

Classifying herds as virus negative on the basis of 20 seronegative 8 or 14 week old pigs (irrespective of whether seropositivity was non-homogeneously distributed within the two age groups) is supported by three arguments. First, there was no passive immunity, which declines within 4–10 weeks [24,25] indicating that sows were likely seronegative. Second, in the current study, unvaccinated herds with seropositive young stock had a mean seroprevalence of 67% in 14 week old pigs (Figure (Figure1).1). When all 20 grower pigs were seronegative the true seroprevalence would be expected to be ≤22%, with 95% confidence. This suggests that young stock might act as sentinels for active virus transmission within a herd: they are either negative or highly positive. Third, both vaccinated and unvaccinated positive herds had a significantly higher proportion of seropositive adults than herds with no seropositive young stock, indicating that these herds had no/little active infection in adults.

The factors that may provide a pool of susceptible pigs and reduce the probability of herd immunity and so aid persistence of PRRSV on pig farms include production of susceptible piglets (approximately 22 per annum per sow) and the movement of pigs between farms, especially breeding stock, currently replaced at 45% per annum in the UK. These risks are correlated and decrease together as herd size decreases. There may be a threshold level when the probability of successful introduction reduces to below 1. In the current study, this appears to be at ~250 sows. So a smaller herd size might reflect an increased probability of reduced risk of introduction of virus and/or virus fadeout from lack of susceptible pigs. The association between fadeout of PRRSV and herd size has been reported previously [10].

Herds with < 250 sows were correlated with multiplier and nucleus herds. Such herds were also more likely to be situated > 2 miles from the next nearest pig unit. It is not possible to state which of these factors, or the combination of factors, assists seronegativity because these farms are more likely to be more biosecure than commercial farms and might be deliberately situated further away from the main pig breeding areas. Consequently, cause and effect relationships cannot be separated. However, biologically, a small population is more likely to lead to virus fade out.

PRRSV antibody negative herds were more prevalent (Model 1) when they were > 2 miles away from the nearest pig unit. Seropositivity was also lower in herds that were more remote from other pig herds so local distant spread appears possible. The mechanisms by which virus may be transmitted between herds is currently not known, although aerosol transmission of PRRSV has been demonstrated over short distances [26,27] and some birds and insects can harbour virus [28,29] and so might transmit virus over longer distances. The association of lower IRPC values in positive herds when statutory pig-free time for visitors was > 48 hours may reflect a possible route of introduction of virus, although not reported previously. It is also likely to correlate with generally high biosecurity. However the virus is transmitted, researchers in Denmark and the UK suggest that between-herd transmission of virus, not via pigs, is possible [1,30].

As well as geographical isolation, purchase of known negative stock and quarantine of stock before introduction onto a farm may limit introduction of PRRSV. Presence of quarantine facilities were not associated with antibody negative herds but were associated with herds that had all seronegative young stock (Model 2), which are likely to have been virus negative (see below). In addition, time that purchased stock spent in isolation was associated with lower IRPC values in pigs in virus positive herds (Model 3). This latter association could occur if pigs in isolation were more likely to be virus negative by the time they entered the unit. Isolation of new stock has been associated with a lower risk of introduction of PRRSV [1,31,8].

A lower mean IRPC in positive herds with purchased gilts rather than homebred replacements would occur if there was a higher probability that purchased gilts were seronegative compared with homebred gilts: this probability would be high if the mean herd seropositivity was higher than the mean of all herds. Purchase of PRRSV negative gilts into a PRRS virus positive herd might lead to disease in the herd if these gilts were infected when pregnant and this may explain some of the irregular disease patterns reported in positive herds [9].

The presence of antibodies in breeding female pigs but not young stock (Figures (Figures22 and and3)3) has two possible explanations. First, gilts were exposed to virus or vaccinated on one farm and then introduced into a negative herd when they were seropositive but virus negative. Second, if virus had been transmitted on the farm in the recent past, but had since faded out, then it would leave seropositive virus negative older parity sows. This is seen in six herds that had seronegative young stock and used homebred replacement gilts (Figure 3a–3f), where older sows were more likely to be seropositive. This suggests fadeout of virus from the herd, since older pigs are more likely to have been present in the herd when virus was circulating. Following fadeout of virus, younger pigs in the herd would not have been exposed to virus and so would remain seronegative. Four of these six herds that used homebred replacements had some seropositive gilts or parity 1 sows (suggesting that virus was present up until quite recently) (Figure 3a, 3c, 3d, 3f). This may suggest either the early stages of fadeout (with younger pigs having not been exposed to virus) or the early stages of an outbreak, with virus in the breeding herd but not yet in the young stock. Two of the profiles of herds that had seronegative young stock and purchased gilts also suggest virus fadeout (Figure 2a, 2f), but the remaining eight had a higher proportion of seropositive younger sows compared with older sows (Figure 2b–2e, 2g–2j). This suggests introduction of antibody positive stock into virus negative herds and a decline in the level of antibodies in older sows because they had been purchased, and presumably exposed, a long time previously and the level of antibodies had waned. These profiles suggest non re-exposure to virus after purchase and therefore a lack of virus in the recipient herd.

It is likely that both truly virus positive and truly virus negative herds that use homebred replacements are the most clinically and immunologically stable, since the former encourages active immunity in pigs before their first gestation and the latter have no virus. Introduction of viraemic stock into positive herds might assist in persistence of PRRSV through re-introduction and would be of concern if a different strain of PRRSV was introduced. Conversely, introduction of negative pigs into a positive herd might cause disease because these gilts would be infected in their first gestation. Totally negative herds are at risk of PRRSV introduction if geographically close to another pig farm, of larger herd size or if purchasing and/or not isolating incoming stock. We are pursuing the development of mathematical models to better understand the transmission dynamics of PRRSV, the patterns of clinical disease it exhibits and appropriate control strategies.

Approximately 51.5% and 64.8% of the total between-herd variance (amongst seropositive herds) were explained in the two multilevel models (Tables 4 and 5) respectively. As a result, the proportion of variation attributable to differences between pens and between pigs was high in both multivariable models. Approximately 37% and 59% of the total variation was attributable to differences between pigs in the two models (Tables 4 and 5) respectively. The collection of data at the pen and pig levels may have accounted for some of this variability. Main sources of variability may include IRPC values between pigs (experimental error and strain variation) as well as presence of maternal antibody and the time of exposure to virus.