Epidemiologic and economic considerations regarding persistently infected cattle during vaccinate-to-live strategies for control of foot-and-mouth disease in FMD-free regions.

Development of a foot-and-mouth disease (FMD) carrier state following FMD virus (FMDV) infection is a well-established phenomenon in cattle. However, the proportion of cattle likely to become carriers and the duration of the carrier state at a herd or population-level are incompletely understood. The objective of this study was to examine the epidemiologic and economic impacts of vaccination-to-live strategy in a disease-free region or country. We developed and simulated scenarios of FMD spread and control in the US livestock population, which included depopulation for a limited period, followed by a vaccinate-to-live strategy with strong biosecurity and movement restrictions. Six scenarios of FMD spread and control were simulated in the InterSpread Plus (ISP) modeling tool. Data on the number of infected and depopulated cattle (by operation types) from ISP model runs were used to estimate the monthly number of infected but not depopulated (potential carrier) cattle after the infection. Using available literature data on the FMD carrier state, we estimated the monthly proportion of carrier cattle (from infected but not depopulated cattle) over time following infection. Among the simulated scenarios, the median (25th, 75th percentile) number of infected cattle ranged from 43,217 (42,819, 55,274) head to 148,907 (75,819, 205,350) head, and the epidemic duration ranged from 20 (11, 30) to 76 (38, 136) days. In general, larger outbreaks occurred when depopulation was carried out through longer periods, and the onset of the vaccination was late (p > 0.05). The estimated proportion of surviving cattle, which were infected and not depopulated and had the potential to become persistently infected ranged from 14 to 35% of total infected cattle. Production losses in beef and dairy sectors were higher when outbreaks started in multiple states simultaneously, but production losses were small compared to trade losses and consumer avoidance losses. These results can be used to inform the consideration of a vaccinate-to-live strategy for FMD outbreaks and the development of appropriate post-outbreak management strategies. Furthermore, this output will enable a more detailed examination of the epidemiologic and economic implications of allowing convalescent cattle to survive and remain in production chains after FMD outbreaks in FMD-free regions.

Parameterization of the durations of phases of foot-and-mouth disease in pigs.

The global interconnectedness of the pig-production industry and the diversity of foot-and-mouth disease (FMD) viruses (FMDVs) currently circulating, makes modeling disease spread and control in FMD-free areas challenging. However, advances in experimental design and transmission studies create opportunities to strengthen our understanding and ability to model FMD transmission. In the current study, we estimated the duration of defined phases of FMDV infection in pigs by using data from a large collection of controlled in vivo experiments. Because the detection of low-levels of viral RNA does not correspond to infectiousness, an experimentally defined minimum threshold of FMDV RNA shedding in oropharyngeal fluids was used to estimate the onset of infectiousness in experiments in which transmission was not evaluated. Animal-level data were used in Accelerated Failure Time models to assess the effect of experimental design factors in the duration of defined phases of FMDV infection: latent, incubation, pre-clinical infectious, clinical infectious, and total infectious periods. The estimated means of the phases were latent: 25 h (95%CI 21, 29), incubation: 70 h (95%CI 64, 76), pre-clinical infectious: 36 h (95%CI 32, 41), clinical infectious: 265 h (95%CI 258, 272) and total infectious: 282 h (95%CI 273, 290). Virus strains and exposure methods had no significant influence on the duration of latency, incubation, or clinical infectious phases. By contrast, the estimated means of the duration of the pre-clinical infectious and total infectious phases were significantly influenced by virus strains, and the duration of the pre-clinical infectious phase was significantly influenced by exposure methods. This study provides disease parameters based on an estimated threshold of the onset of infectiousness and a probability distribution representing the end of infectiousness. Disease parameters that incorporate experimentally-based quantitative proxies to define phases of FMDV infection may improve planning and preparedness for FMD.

Parameterization of the Durations of Phases of Foot-And-Mouth Disease in Cattle.

The objective of the current study was to update parameterization of mathematical simulation models for foot-and-mouth disease (FMD) spread in cattle utilizing recent knowledge of FMD virus (FMDV) pathogenesis and infection dynamics to estimate the duration of distinct phases of FMD. Specifically, the durations of incubation, latent, and infectious periods were estimated for 3 serotypes (O, Asia1, and A) of FMDV, individually and collectively (pan-serotypic). Animal-level data were used in Accelerated Failure Time (AFT) models to estimate the duration of the defined phases of infection, while also investigating the influence of factors related to the experimental design (exposure methods) and virus serotype on disease progression. Substantial influences upon the estimated duration of distinct phases of FMD included the quantity of viral shedding used as a proxy for the onset of infectiousness, virus serotypes, and experimental exposure methods. The use of detection of any viral RNA in nasal secretions as a proxy of infectiousness lengthened the total infectious period compared to use of threshold-based detection. Additionally, the experimental system used to infect the animals also had significant effects on the duration of distinct phases of disease. Overall, the mean [95% Confidence Interval (CI)] durations of pan-serotype disease phases in cattle were estimated to be: incubation phase = 3.6 days (2.7-4.8), latent phase = 1.5 days (1.1-2.1), subclinical infectious phase = 2.2 days (1.5-3.5), clinical infectious phase = 8.5 days (6.2-11.6), and total infectious phase = 10.8 days (8.2-14.2). This study highlights the importance of identifying appropriate proxy measures to define the onset and duration of infectiousness in FMDV-infected cattle in the absence of actual transmission data. Additionally, it is demonstrated herein that factors associated with experimental design, such as virus exposure methods, may significantly affect disease progression in individual animals and should be considered when data is extrapolated from experimental studies. Given limitations in experimental data availability, pan-serotypic parameters which include all routes of exposure and a threshold-defined onset of infectiousness may be the most robust parameters for exploratory disease spread modeling approaches, when information on the specific virus of interest is not available.

Quantitative impacts of incubation phase transmission of foot-and-mouth disease virus.

The current investigation applied a Bayesian modeling approach to a unique experimental transmission study to estimate the occurrence of transmission of foot-and-mouth disease (FMD) during the incubation phase amongst group-housed pigs. The primary outcome was that transmission occurred approximately one day prior to development of visible signs of disease (posterior median 21 hours, 95% CI: 1.1-45.0). Updated disease state durations were incorporated into a simulation model to examine the importance of addressing preclinical transmission in the face of robust response measures. Simulation of FMD outbreaks in the US pig production sector demonstrated that including a preclinical infectious period of one day would result in a 40% increase in the median number of farms affected (166 additional farms and 664,912 pigs euthanized) compared to the scenario of no preclinical transmission, assuming suboptimal outbreak response. These findings emphasize the importance of considering transmission of FMD during the incubation phase in modeling and response planning.

Risk of environmental exposure to small coccidia from wild canid feces in rural Ohio.

OBJECTIVE To determine the extent of environmental exposure to heteroxenous coccidia from wild canid feces in southeastern Ohio. SAMPLE 285 presumed wild canid fecal samples collected across an ecological system in southeastern Ohio. PROCEDURES Morphological classification and molecular analysis were used to determine the canid genus for collected fecal samples. Microscopic and molecular analysis were used to detect coccidian oocysts and DNA. Several variables were analyzed for associations with coccidian DNA detection or prevalence. RESULTS Coccidian DNA was detected in 51 of 285 (17.9%) fecal samples. Of those positive samples, 1% (95% confidence interval, 0.4% to 3%) had positive results for Hammondia heydorni and none had positive results for Neospora caninum, for an estimated environmental N caninum prevalence of 0% (95% confidence interval, 0% to 7%)/1-km2 hexagonal area evaluated. Morphological classification revealed that 78.9% (225/285) of fecal samples were from coyotes and 17.2% (49/285) were from foxes. No difference in proportions of coccidian DNA-positive fecal samples was identified among canid species. Environmental temperature and fecal freshness were associated with coccidian DNA detection. Land use type, relative canid density, and cattle density were not associated with the prevalence of coccidian DNA-positive samples. CONCLUSIONS AND CLINICAL RELEVANCE The low prevalence of coccidia shed in wild canid feces in this study, including the estimated 0% environmental prevalence of N caninum, suggested that the role of the oocyst environmental phase in coccidia transmission to ruminants is likely minor in rural southeastern Ohio.

Foot-and-Mouth Disease Infection Dynamics in Contact-Exposed Pigs Are Determined by the Estimated Exposure Dose.

The quantitative relationship between the exposure dose of foot-and-mouth disease virus (FMDV) and subsequent infection dynamics has been demonstrated through controlled inoculation studies in various species. However, similar quantitation of viral doses has not been achieved during contact exposure experiments due to the intrinsic difficulty of measuring the virus quantities exchanged between animals. In the current study, novel modeling techniques were utilized to investigate FMDV infection dynamics in groups of pigs that had been contact-exposed to FMDV-infected donors shedding varying levels of virus, as well as in pigs inoculated via the intra-oropharyngeal (IOP) route. Estimated virus exposure doses were modeled and were found to be statistically significantly associated with the dynamics of FMDV RNA detection in serum and oropharyngeal fluid (OPF), and with the time to onset of clinical disease. The minimum estimated shedding quantity in OPF that defined infectiousness of donor pigs was 6.55 log10 genome copy numbers (GCN)/ml (95% CI 6.11, 6.98), which delineated the transition from the latent to infectious phase of disease which occurred during the incubation phase. This quantity corresponded to a minimum estimated exposure dose of 5.07 log10 GCN/ml (95% CI 4.25, 5.89) in contact-exposed pigs. Thus, we demonstrated that a threshold quantity of FMDV detection in donor pigs was necessary in order to achieve transmission by direct contact. The outcomes from this investigation demonstrate that variability of infection dynamics which occurs during the progression of FMD in naturally exposed pigs can be partially attributed to variations in exposure dose. Moreover, these modeling approaches for dose-quantitation may be retrospectively applied to contact-exposure experiments or field scenarios. Hence, robust information could be incorporated into models used to evaluate FMD spread and control.

Use of a combination of routine hematologic and biochemical test results in a logistic regression model as a diagnostic aid for the diagnosis of hypoadrenocorticism in dogs.

OBJECTIVE To assess the discriminatory value for corticosteroid-induced alkaline phosphatase (CiALP) activity and other variables that can be measured routinely on a CBC and biochemical analysis for the diagnosis of hypoadrenocorticism in dogs. SAMPLE Medical records of 57 dogs with confirmed hypoadrenocorticism and 57 control dogs in which hypoadrenocorticism was suspected but ruled out. PROCEDURES A retrospective case-control study was conducted. Dogs were included if a CBC and complete biochemical analysis had been performed. Dogs with iatrogenic hypoadrenocorticism and dogs treated previously with glucocorticoids were excluded. Cortisol concentration for dogs with hypoadrenocorticism was ≤ 2 µg/dL both before and after ACTH administration. Cortisol concentration for control dogs was > 4 µg/dL before or after ACTH administration. RESULTS Area under the receiver operating characteristic (ROC) curve for CiALP activity was low (0.646; 95% confidence interval, 0.494 to 0.798). Area under the ROC curve for a model that combined the CiALP activity, Na-to-K ratio, eosinophil count, activity of creatine kinase, and concentrations of SUN and albumin was high (0.994; 95% confidence interval, 0.982 to 1.000). Results for this model could be used to correctly classify all dogs, except for 1 dog with hypoadrenocorticism and no electrolyte abnormalities. CONCLUSIONS AND CLINICAL RELEVANCE CiALP activity alone cannot be used as a reliable diagnostic test for hypoadrenocorticism in dogs. Combined results for CiALP activity, Na-to-K ratio, eosinophil count, creatine kinase activity, and concentrations of SUN and albumin provided an excellent means to discriminate between hypoadrenocorticism and diseases that mimic hypoadrenocorticism.

Host species heterogeneity in the epidemiology of Nesopora caninum.

Pathogen transmission across species drives disease emergence; however, mechanisms by which multi-host pathogens cross species boundaries are not well identified. This knowledge gap prevents integrated and targeted control in an epidemiologically continuous ecosystem. Our goal is to describe the impact of host species heterogeneity on the epidemiology of Neospora caninum circulating between livestock and wildlife in southeastern Ohio. We collected biological samples from Père David's deer (Elaphurus davidianus) located at an outdoor wildlife conservation center; from cattle raised at farms adjacent to the center; and from wild white-tailed deer that roamed across farm and center boundaries. We designed nested infectious disease models of competing hypotheses about transmission and used collected data to fit the models, thereby estimating important immunological and transmission quantities which describe the species-specific contribution to the persistence of this pathogen in the community. We applied these data and models to suggest appropriate species-specific disease control methods. Results show that immunity in cattle and Pére David's deer wanes over time, while in white-tailed deer immunity appears to be lifelong. Transmission quantities for cattle were estimated at values below the threshold for an outbreak (Rt < 1), meaning that chains of transmission are not maintained within this population and infections must occur due to reintroduction from an outside source. Pére David's deer and white-tailed deer both could maintain continuous chains of transmission within their group (Rt > 1). Therefore, we propose that control of contact with outside sources will be useful for disease control in cattle; boosting immunity with vaccines might be an avenue to prevent infection in cattle and Père David's deer. White-tailed deer are a potential maintenance host for infection and require further study to determine optimal control methods. Community-level investigations like this allow us to better evaluate heterogeneities in transmission processes that ultimately guide targeted control.

Transmission of Foot-and-Mouth Disease Virus during the Incubation Period in Pigs.

Understanding the quantitative characteristics of a pathogen's capability to transmit during distinct phases of infection is important to enable accurate predictions of the spread and impact of a disease outbreak. In the current investigation, the potential for transmission of foot-and-mouth disease virus (FMDV) during the incubation (preclinical) period of infection was investigated in seven groups of pigs that were sequentially exposed to a group of donor pigs that were infected by simulated-natural inoculation. Contact-exposed pigs were comingled with infected donors through successive 8-h time slots spanning from 8 to 64 h post-inoculation (hpi) of the donor pigs. The transition from latent to infectious periods in the donor pigs was clearly defined by successful transmission of foot-and-mouth disease (FMD) to all contact pigs that were exposed to the donors from 24 hpi and later. This onset of infectiousness occurred concurrent with detection of viremia, but approximately 24 h prior to the first appearance of clinical signs of FMD in the donors. Thus, the latent period of infection ended approximately 24 h before the end of the incubation period. There were significant differences between contact-exposed groups in the time elapsed from virus exposure to the first detection of FMDV shedding, viremia, and clinical lesions. Specifically, the onset and progression of clinical FMD were more rapid in pigs that had been exposed to the donor pigs during more advanced phases of disease, suggesting that these animals had received a higher effective challenge dose. These results demonstrate transmission and dissemination of FMD within groups of pigs during the incubation period of infection. Furthermore, these findings suggest that under current conditions, shedding of FMDV in oropharyngeal fluids is a more precise proxy for FMDV infectiousness than clinical signs of infection. These findings may impact modeling of the propagation of FMD outbreaks that initiate in pig holdings and should be considered when designing FMD control strategies.

Effect of host species diversity on multiparasite systems in rodent communities.

Reduced species diversity has been suggested to increase transmission rates and prevalence of infectious diseases. While this theory has been studied mostly in single pathogen systems, little is known regarding multiple pathogens systems in vertebrates at the community level. The aim of this study was to evaluate the effect of host richness and diversity on multiple parasite systems on a local scale. We captured small rodents and collected feces in three different vegetation types in a natural protected area in Janos, Chihuahua, Mexico. The flotation technique was used to identify parasite eggs or oocysts. Analysis of linear correlations was conducted between parasite prevalence and host and parasite diversity and richness. Negative correlation was detected between parasite prevalence and host diversity (p = 0.02 r(2) =-0.86), but no significant correlations was detected between parasite prevalence and host richness or parasite diversity or richness. Our study shows that at local scale, host diversity could affect multiple parasite systems in the same way that single pathogens do. Further studies should be performed on larger temporal and spatial scales to more thoroughly investigate the correlation observed in our analysis.