A method to provide improved dose-response estimates for airborne pathogens in animals: an example using porcine reproductive and respiratory syndrome virus.

This paper describes a method to provide improved probability estimates that exposure to a specific dose of an airborne infectious pathogen will result in animal infection. Individual animals were exposed to a specific dose of airborne pathogen. Following exposure, animals were individually housed and monitored for evidence of infection. The detection of specific antibodies and/or the pathogen in diagnostic specimens was evidence that the exposure dose resulted in infection. If replicated over a range of doses, the results can be used to derive a dose-response curve for a variety of animal species and infectious pathogens. This information is useful in estimating the likelihood of infection associated with exposure to airborne infectious microorganisms. Applications include predicting the risk of transmission associated with exposure to airborne pathogens, modeling the transmission of airborne pathogens, and determining requirements for effective exposure doses for vaccines delivered in aerosols.

Probability of porcine reproductive and respiratory syndrome (PRRS) virus infection as a function of exposure route and dose.

At the most elemental level, the design of effective strategies to control and/or eliminate porcine reproductive and respiratory syndrome (PRRS) virus depend on an accurate and comprehensive understanding of virus transmission. As a general rule, transmission is highly dependent on the route of exposure and the dose of virus. The objective of this study was to derive PRRS virus isolate VR-2332 dose-response curves for oral and intranasal routes of exposure, i.e., determine the probability that a specific virus dose would result in infection. Individually housed pigs approximately 21 days of age were exposed to specific doses of PRRS virus isolate VR-2332 by either oral or intranasal routes. Positive controls were intramuscularly inoculated with 10(2.2) 50% tissue culture infective dose (TCID50) of PRRS virus and negative controls were orally administered 100ml of diluent with no virus. Pigs were monitored for evidence of infection for 21 days following exposure, i.e., serum samples were collected on days 0, 7, 14, 21, and tested for virus and PRRS virus-specific antibodies. Dose-response curves and 95% confidence intervals for oral and intranasal routes of exposure were derived using logistic models (logit and probit). The infectious dose50 (ID50) for oral exposure was estimated to be 10(5.3) TCID50 (95% CI, 10(4.6) and 10(5.9)); the ID50 for intranasal exposure was estimated to be 10(4.0) TCID50 (95% CI, 10(3.0) and 10(5.0)). Given these estimates, it is worth noting that intramuscular exposure of animals to 10(2.2) TCID50 (positive controls) resulted in infection in all animals. Thus pigs were the most susceptible to infection via parenteral exposure.

Descriptive epidemiology of postnatal bovine viral diarrhea virus infection in intensively managed dairy heifers.

OBJECTIVE: To evaluate risk of bovine viral diarrhea virus (BVDV) infection between birth and 9 months of age for dairy replacement heifers raised under typical dry-lot management conditions. DESIGN: Longitudinal observational study. ANIMALS: 446 calves. PROCEDURE: Calves were randomly selected from 2 dairies that used killed and modified-live BVDV vaccines. Repeated serologic and BVDV polymerase chain reaction assays were used to estimate risk of BVDV infection in calves of various ages (1 to 60 days; 61 to 100 days; 101 days to 9 months) and to estimate overall infection rate by 9 months of age. RESULTS: Risk of BVDV infection increased with age (maximum risk, 150 to 260 days). Proportion of calves infected with BVDV by 9 months of age was higher for dairy A (0.665), compared with dairy B (0.357). Percentage infected with BVDV type I did not differ between dairy A (18.2%) and dairy B (15.2%), whereas percentage infected with BVDV type II for dairy A (50%) was twice that for dairy B (21%). Between 210 and 220 days of age, infection with BVDV regardless of type was > 1.3%/d on dairy A and 0.5%/d on dairy B. CONCLUSIONS AND CLINICAL RELEVANCE: Under dry-lot conditions, a considerable amount of BVDV infection may occur before 9 months of age. Risk of infection increases with age. Although dairies may appear to have similar management practices, there can be considerably different risks of BVDV infection among dairies.

Effect of calfhood vaccination on transmission of bovine viral diarrhea virus under typical drylot dairy conditions.

OBJECTIVE: To estimate transmission of bovine viral diarrhea virus (BVDV) and crude morbidity and mortality ratios in BVDV-vaccinated and unvaccinated dairy heifer calves managed under typical dairy drylot conditions. DESIGN: Randomized clinical trial. ANIMALS: 106 female Holstein calves. PROCEDURE: Seroconversion rates for BVDV types I and II and proportional morbidity and mortality ratios were compared between calves given a killed BVDV type-I vaccine at 15 days of age and a modified-live BVDV type-I vaccine at 40 to 45 days of age (n = 53) and calves given no BVDV vaccines (53). Sera were collected at 45-day intervals as calves moved from individual hutches to corrals holding increasingly larger numbers of calves. Seroconversion was used as evidence of exposure to BVDV. RESULTS: Crude proportional morbidity (0.16) and mortality (0.17) ratios for control calves did not differ significantly from those of vaccinated calves (0.28 and 0.12, respectively). The proportion of control calves that seroconverted to BVDV type I through 9 months of age (0.629) was significantly higher than that of vaccinated calves that seroconverted, unrelated to vaccination, during the same period (0.536). Estimated overall protective effect of vaccination against BVDV type I through 4 to 9 months of age was 48%. The proportion of control calves that seroconverted to BVDV type II (0.356) was not different from that of vaccinated calves (0.470). CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggest that calfhood vaccination may be an appropriate strategy to help reduce short-term transmission of some but not necessarily all strains of BVDV.

Pooled-sample testing as a herd-screening tool for detection of bovine viral diarrhea virus persistently infected cattle.

The study was conducted to develop methodology for least-cost strategies for using polymerase chain reaction (PCR)/probe testing of pooled blood samples to identify animals in a herd persistently infected with bovine viral diarrhea virus (BVDV). Cost was estimated for 5 protocols using Monte Carlo simulations for herd prevalences of BVDV persistent infection (BVDV-PI) ranging from 0.5% to 3%, assuming a cost for a PCR/probe test of $20. The protocol associated with the least cost per cow involved an initial testing of pools followed by repooling and testing of positive pools. For a herd prevalence of 1%, the least cost per cow was $2.64 (95% prediction interval = $1.72, $3.68), where pool sizes for the initial and repooled testing were 20 and 5 blood samples per pool, respectively. Optimization of the least cost for pooled-sample testing depended on how well a presumed prevalence of BVDV-PI approximated the true prevalence of BVDV infection in the herd. As prevalence increased beyond 3%, the least cost increased, thereby diminishing the competitive benefit of pooled testing. The protocols presented for sample pooling have general application to screening or surveillance using a sensitive diagnostic test to detect very low prevalence diseases or pathogens in flocks or herds.

Effect of weaning time and associated management practices on postweaning chronic diarrhea in captive rhesus monkeys (Macaca mulatta).

OBJECTIVE: Our purpose was to assess the extent to which early weaning and other weaning-management factors affect development of postweaning chronic diarrhea in captive rhesus monkeys at the California Regional Primate Research Center between 1992 and 1995. METHODS: Data for weaning, management, and onset of diarrhea were obtained from daily records. The Cox proportional hazard model was used to assess whether the risk of chronic diarrhea was related to early weaning. RESULTS: Monkeys that were lighter at weaning had a threefold increase in risk of postweaning chronic diarrhea (P = 0.07), compared with that in heavier monkeys. An episode of preweaning diarrhea increased the risk of postweaning chronic diarrhea twofold (P = 0.08). Relocation of monkeys to outdoor facilities in the fall was associated with a fivefold decrease in risk (P < 0.001), compared with that of other seasons, and weaning in 1993 was associated with a twofold decrease in risk, compared with that of other years (P = 0.04). CONCLUSIONS: Multiple factors need to be considered for prevention of postweaning chronic diarrhea, including weaning weight, preweaning diarrhea, season weaned, and weaning conditions that change from year to year.