Comparison of vaccination schedules for foot-and-mouth disease among cattle and sheep in Mongolia.

Vaccines are a critical tool for the control strategy for foot-and-mouth disease (FMD) in Mongolia where sporadic outbreaks regularly occur. A two-dose primary vaccination course is recommended for most commercial vaccines though this can be logistically challenging to deliver among nomadic pastoralist systems which predominate in the country. Although there is evidence that very high potency vaccines can provide prolonged duration of immunity, this has not been demonstrated under field conditions using commercially available vaccines. This study compared neutralizing titres to a O/ME-SA/Panasia strain over a 6-month period following either a two-dose primary course or a single double-dose vaccination among Mongolian sheep and cattle using a 6.0 PD50 vaccine. Titers were not significantly different between groups except in sheep at six-months post vaccination when the single double-dose group had significantly lower titers. These results indicate the single double-dose regimen may be a cost-effective approach for vaccination campaigns supporting FMD control in Mongolia.

Economic Considerations for Advancement Through the Progressive Control Pathway: Cost-Benefit Analysis of an FMD Disease-Free Zone in Punjab Province, Pakistan.

Foot-and-mouth disease (FMD) is a priority disease of livestock in Pakistan, which was classified in stage 2 of the Progressive Control Pathway (PCP-FMD) in 2015, aiming to reduce disease impact. Further progression requires efforts to reduce viral circulation that may ultimately result in being awarded official disease-free status by the World Organisation for Animal Health [Office International des Epizooties (OIE)]. Typically, FMD control is reliant on the extensive use of vaccines, requiring careful consideration of the costs and benefits to ensure investment is likely to provide a positive return. This study conducted a cost-benefit analysis (CBA) for a proposed zone within Punjab Province, Pakistan. Benefits were assumed to come from averted production losses and treatment costs and the costs based on typical measures required for establishing a disease-free zone. To estimate the impact of FMD at the farm level, models were created to estimate effects on milk production, offtakes, and changes in herd value over a 5-year period with different parameters used to represent the production systems present. Control strategy costs incorporated aspects of vaccination, surveillance, sanitary measures, program management, stakeholder engagement, preparatory studies, training, and capacity building. The results indicated a median benefit-cost ratio of 1.03 (90% central range 0.37, 1.63) with a median net present value of 1.99 billion Pakistan Rupees (90% central range -37.7, 37.0). The greatest cost was due to vaccination at 56%, followed by sanitary measures (including implementing and maintaining an animal ID system and quarantine stations around the zone) at 41%. Although the median benefit-cost ratio and net present value indicated that investment is likely to generate a positive return, the large variation indicates caution in interpreting the results and it is possible that an increase in animal value through new export markets will be required. Further refinement in our knowledge of disease impact and the details of the control strategy are needed. Moreover, there are implications regarding vaccine security, since the strategy is reliant on the steady provision of quality vaccines in order to achieve the anticipated benefits, raising important issues on vaccine availability for countries to maintain lucrative export markets for FMD.

Considerations for design and implementation of vaccine field trials for novel foot-and-mouth disease vaccines.

Vaccines are commonly used to control Foot-and-Mouth Disease (FMD) in endemic regions and form an important part of contingency plans for FMD-free countries. Conventional FMD vaccines have numerous limitations, and the U.S. government supports the development of next-generation vaccines. In the U.S., vaccine efficacy is typically demonstrated through experimental vaccination and challenge of animals using the World Organization for Animal Health (OIE) standards. Although conventional challenge and immunogenicity studies provide useful information, they have limitations and results do not always accurately predict field performance. Consequently, there is a need to test next-generation vaccines under field conditions to gain a better understanding of field performance to inform policy decisions and support their viability as a commercial product. In June 2017, an expert consultation was organised to discuss and define an optimal field study design for novel FMD vaccines. Cattle were the primary species considered, although parallel strategies for swine and small ruminants were also discussed. Many methodological and logistical considerations in the study design were identified, including: (1) study site selection and the importance of baseline studies to understand exposure risk, (2) ethics of using a placebo and assessing equivalence with conventional vaccines, (3) merits of using individual randomised versus cluster randomised trials, (4) preventive versus reactive vaccination, and (5) methods of randomisation and blinding. The proposed optimal study design was a multicentre (i.e. farm), three-arm, double-blind randomised controlled trial comparing groups receiving the novel vaccine to a conventional vaccine group and a placebo group. Large farms in areas of high exposure risk were identified as ideal study sites, and the primary study outcome was susceptibility to disease or infection, during a six-month observation period, following a single dose of vaccine. This report provides a summary of the important issues to consider when designing a field efficacy study in livestock and proposes a study design that could be utilised for novel FMD vaccines.

Livestock mortality and offtake in sheep and goat flocks of livestock owners making use of services offered by paravets in West Afghanistan.

In the present study, we quantified the effect of livestock services provided through paravets (intermediate-level training in veterinary medicine) on mortality and offtake of small ruminants in Western Afghanistan for the years 2010, 2011 and 2013. We compared mortality in adult and in young stock, and offtake of young stock of 120 livestock owners that made use of the paravet services (Users) with 120 livestock owners who did not make use of these services (Non-users). Security issues in the districts under study influenced the choice of villages. Within villages, livestock owners were purposively selected based on their known use of the services, including the provision of biologicals such as anthelmintics and vaccines. In addition, we subdivided both categories into 'partial' and 'full' based on the intensity of use of biologicals. Paravets were not only trained on preventive and curative veterinary medicine, they were also trained in extension and trained on adhering to a cold-chain and applying quality biologicals. For Non-users there was the possibility to buy biologicals through a local market or bazaar. In Afghanistan, local markets have an extensive supply of vaccines, anthelmintics, and medicines from a variety of sources, often not handled appropriately and therefore of varying quality. The results indicated that livestock owners making partial or full use of the paravet services had statistically significant better animal health and production results. The mortalities in adult stock, expressed as Incidence Rate Ratios (IRRs), for the partial-Users and full-Users categories were estimated to be respectively 0.80 and 0.73 times the mortality observed in the partial Non-users', the reference category. A similar result was observed for young stock mortality with estimated IRRs of 0.81 and 0.77 for partial and full-Users category respectively. The offtake for partial- and full-Users category livestock owners were 1.24 and 1.21 times higher compared with the reference category. In conclusion, we demonstrated significant improvement of health and production parameters in small ruminants' flocks of owners making use of the services of the DCA-trained paravets, emphasizing the importance of this sustainable and effective system of private veterinary service delivery in Afghanistan.

No long-term influence of movement restriction regulations on the contact-structure between and within cattle holding types in the Netherlands.

BACKGROUND: More and more countries hold databases on cattle movements. The primary purpose of the registration of cattle movements is to provide data for quick tracing of contagious animals in case of disease outbreaks and food safety scares. Nevertheless, these data can also be used for analytical studies to get insight into the nature of the contact structure between and within cattle holding types. This paper focuses on the effect post-2001 FMD movement regulations have had on the number of cattle movements between different and within the same cattle holding types. Important characteristics and dynamics of cattle movement patterns of Dutch cattle holding types were identified using data on cattle movements after the 2001 FMD outbreak. RESULTS: The results showed that in 2001, just after the FMD outbreak when strict movement restriction regulations were in force, a reduced number of cattle movements was seen compared to before the FMD outbreak. However, the number of cattle movements off-farm for live trade and the number of imported cattle increased in the period 2002-2004 to higher levels than expected, i.e. to levels almost as high as before the FMD outbreak, despite operative movement restriction regulations. As the number of cattle movements to and from traders strongly decreased just after the FMD outbreak in 2001, traders regained their central role again in the network in the years 2002-2004. CONCLUSIONS: Quantifying the Dutch cattle contact structure between and within holding types up to 3.5 years after the FMD outbreak gave evidence that the post-FMD movement restriction regulations were not able to reduce the number of cattle movements in the longer term. With that the risk of a large epidemic increased. Quantifying contact structures based on animal movement data between different and within the same cattle holding types is important for targeting disease control and for assessing compliance with legislation.

The effect of an acidified, ionized copper sulphate solution on digital dermatitis in dairy cows.

Digital dermatitis (DD) is the most important infectious claw disorder in dairy cattle and herd-based foot bathing with antibacterials, such as 4% formalin, is often used to prevent it. However, there is a lack of long-term studies of the effectiveness of such regimes and in this study the preventive and curative effect of 4% formalin was compared with that of an acidified, ionized copper sulphate solution over a 4-month period on a commercial 120-cow dairy farm. The cows were walked through a split-leg footbath where left claws were treated with an acidified copper solution twice daily for 5 days/week, while right claws were treated with 4% formalin twice daily for 1 day/every second week. Hind claws were scored for the presence and severity of DD in a trimming chute at the start of the study and every 4 weeks throughout the study period. At the start of the study 21/110 cows had ulcerative DD lesions with 10 on the left hind foot, 8 on the right and 3 on both. These lesions, as well as any new lesions which arose during the study, were treated with chlortetracycline spray. During the study 440 observations were made and seven new DD lesions were recorded on left feet (copper treated) and 20 on right feet (formalin treated). Based on survival analysis, the risk of developing a new ulcerative DD lesion on copper-treated (left hind) feet was almost three times less (RR=0.37, 95% CI 0.16-0.91) than formalin-treated (right hind) feet. Cure rates of DD lesions were not different between copper and formalin.

Prevalence, prediction and risk factors of enteropathogens in normal and non-normal faeces of young Dutch dairy calves.

Between January and April 2007, 424 calves under 22 days of age from 108 Dutch dairy herds were sampled to estimate the prevalence of non-normal faeces ('custard-like'-yellowish-coloured with custard consistency or diarrhoea: watery-like faeces) and the shedding of enteropathogens Escherichia coli K99 (E. coli), Coronavirus, Cryptosporidium parvum (C. parvum), Rotavirus and Clostridium perfringens (Cl. perfringens). In addition, information was collected on animal characteristics and herd-management practices. The probability of detecting each one of five enteropathogens given a calf with 'custard-like' faeces or diarrhoea was estimated using Bayes' rule and was based on the predicted probabilities from a multinominal model including each of five enteropathogens as independent variables. In addition, putative risk factors for the presence of each of five enteropathogens were analysed using logistic regression models with random herd effects. Fifty-seven percent of calves had faeces of normal colour (brownish) and consistency (firm), 23.8% (95%CI: 19.8-28.2%) had 'custard-like' faeces and 19.1% (95%CI: 15.5-23.2%) had diarrhoea. E. coli was the least detected enteropathogen (2.6% (95%CI: 1.3-4.6%) of calves, 9% (95%CI: 5-16%) of herds) and Cl. perfringens was most detected (54.0% (95%CI: 49.1-58.8%) of calves, 85% (95%CI: 77-91%) of herds). E. coli and Coronavirus were detected incidentally in only one or two calves per herd, whereas C. parvum and Cl. perfringens were frequently detected in up to four calves per herd. For calves with 'custard-like' faeces, the probability of detecting Rotavirus from a calf in its first week of age was 0.31 whereas for a calf in its second week, there was a 0.66 probability of detecting C. parvum. The probabilities of detecting E. coli, Rotavirus and C. parvum in calves with diarrhoea in their first week of age were 0.10, 0.20 and 0.43, respectively. In calves with diarrhoea between 1 and 2 weeks of age, the probability of detecting enteropathogens was 0.43 for C. parvum. None of the tested enteropathogens were related to 'custard-like' faeces or diarrhoea in the third week of age. Putative risk factors for E. coli, Coronavirus and C. parvum included the presence of peer-calves shedding Coronavirus, C. parvum or Rotavirus, respectively. Additionally, managerial risk factors such as non-optimal hygienic housing (for Coronavirus) and the routine use of antibiotics for diarrhoeic calves (for C. parvum) were found. No animal or managerial factors were associated with shedding of Cl. perfringens.

Clinical course of digital dermatitis lesions in an endemically infected herd without preventive herd strategies.

Lactating Holstein-Friesian dairy cows in four separately housed groups in a herd with endemic digital dermatitis (DD) were monitored weekly for 4 weeks in December 2004 for the presence of and transition between five stages (M0-M4) of DD. Cows were also monitored for the presence of heel horn erosion (HHE) and interdigital hyperplasia. Prior to the study, two groups had been housed indoors on a high or low energy ration, one group had been grazed and one was a dry cow group. All cows received the same ration during the period of investigation. 'Active infection' was defined as transition from M0, M1, M3 or M4 to M2 and 'resolving M2 lesions' were defined as transition from M2 to another stage. M2 lesions were diagnosed on 106 occasions in the hind claws of 49 (36%) of 138 dairy cows; both hind claws were affected in nine cases (18%). M2 lesions were more often painful on palpation than other stages; 94% of M2 lesions were located plantar-medially near the interdigital cleft and 71% had a diameter of 2-4 cm. More M1 lesions than other stages were found within the interdigital space. When interdigital hyperplasia was present, claws were always concurrently affected by DD. The baseline incidence for 'active infection' was 6% per week, increasing to 11% when HHE was present, 14% when cows were previously housed indoors and fed a high energy ration and 16% when cows were 60-120 days in lactation. Topical treatment with chlortetracycline resulted in resolution from M2 of 79% per week. There were no significant effects of group, stage of lactation, parity or HHE on resolution of M2 lesions.

Quantification of vertical and horizontal transmission of Neospora caninum infection in Dutch dairy herds.

Ninety-six of 108 randomly selected Dutch dairy herds had one or more cows with a positive serostatus for N. caninum. In these 96 herds, we have quantified the probabilities of vertical transmission (VT) and horizontal transmission (HT) of N. caninum infection by combining serostatus and pedigree data in 4091 dam-daughter pairs. The probability of animals infected by vertical transmission during pregnancy (Prob(VT)) was calculated as the proportion of seropositive daughters among daughters of seropositive dams. The probability of animals infected by horizontal transmission (Prob(HT)) was the proportion of seropositive daughters among daughters of seronegative dams. These probabilities were calculated after the frequencies of observed dam-daughter combinations were corrected for (1) imperfect test-characteristics, (2) underestimation of horizontal transmission in situations that seronegative dams were horizontally infected after the birth of their daughters and (3) overestimation of vertical transmission in situations that seronegative daughters born from seropositive dams were horizontally infected. The incidence rate for horizontal transmission was calculated based on Prob(HT) and the average age of the animals in these herds. Based on the analysis of dam-daughter serology, Prob(VT) was 61.8% (95% CI: 57.5-66.0%) and Prob(HT) was 3.3% (95% CI: 2.7-3.9%). After adjusting the observed frequencies for imperfect test-characteristics, underestimation of horizontal transmission and overestimation of vertical transmission, Prob(VT) decreased to 44.9% (95% CI: 40.0-49.9%) while Prob(HT) increased to 4.5% (95% CI: 3.9-5.2%). Prob(HT) corresponded with an incidence rate for horizontal transmission of 1.4 (95% CI: 1.2-1.7) infections per 100 cow-years at risk. When stratifying herds for the presence of farm dogs, Prob(HT) was higher (5.5% (95% CI: 4.6-6.4%)) in herds with farm dogs than in herds without farm dogs (2.3% (95% CI: 1.5-3.4%)). When stratifying for within-herd seroprevalence, Prob(HT) was higher (10.3% (95% CI: 8.6-12.2%)) in herds with high (> or =10%) within-herd seroprevalence compared with herds with low (<10%) within-herd seroprevalence (2.0% (95% CI: 1.5-2.6%)). Although there was this relation between Prob(HT) and within-herd seroprevalence (crude OR(PREV) = 5.7 (95% CI: 4.0-7.9)), in herds without farm dogs, this relationship was no longer statistical significant (OR(PREV|DOG-) = 1.9 (95% CI: 0.7-5.5)). It indicated that the association between seroprevalence and Prob(HT) depended largely on the presence of farm dogs. In addition, when looking for the presence of specific age-groups with significantly higher seroprevalence compared with the rest of the herd, there were 7 herds in which two or more horizontally-infected animals were present in specific age-groups. This was an indication of a recent point-source exposure to N. caninum. These results reiterate the current control strategies to apply strict dog-management measures as well as to minimize within-herd seroprevalence by monitoring serostatus of animals.

Factors associated with variation in Neospora caninum bulk-milk S/P ratios in initially bulk-milk negative testing Dutch dairy herds.

We conducted a study on 81 initially bulk-milk ELISA negative dairy herds taken from a random sample of Dutch dairy herds to evaluate variation in bulk-milk S/P ratios and to study reasons for bulk-milk conversion. These herds were repeatedly (3-month intervals) tested between April 2004 and August 2005 and serostatus of all animals had previously been established as negative (N), low-positive (LP) or high-positive (HP). Of these herds, herd- and test-related factors associated with variation in sample over positive (S/P) ratios were analysed using a multivariable linear-mixed model with 'herd' as random effect. In addition, changes of animal serostatus in converting herds were described. S/P ratios were calculated as the optical density of the bulk-milk sample minus the optical density of the negative serum control divided by the difference in optical density between the positive and negative serum control. Sixteen bulk-milk conversions in 12 dairy herds were seen with few indications of serological conversion in lactating cattle except for one herd in which recrudescence of infection appeared likely in nine cows. The effect of HP serostatus on bulk-milk S/P ratio was 2-3 times stronger compared with LP serostatus. In addition, bulk-milk S/P-ratio increased when the proportion of HP animals between 1 and 60 days in milk increased and decreased when the average milk-production level of the herd increased. Besides these herd-related factors, the use of different ELISA-testkits between test rounds had a significant effect on the S/P-ratio in bulk-milk samples.

Use of an enzyme-linked immunosorbent assay in bulk milk to estimate the prevalence of Neospora caninum on dairy farms in Prince Edward Island, Canada.

This study evaluated the use of bulk milk as a diagnostic tool for estimation of herd-level Neospora caninum exposure in Atlantic Canada; it was used to estimate the prevalence of dairy farms with a within-herd N. caninum-seroprevalence > or = 15% in Prince Edward Island (PEI). The variation over time of N. caninum antibodies in bulk milk is also reported. Skimmed bulk milk and individual serum samples were analyzed for N. caninum antibodies by using an enzyme-linked immunosorbent assay (ELISA). Bulk milk samples were collected in May 2004 (n = 235), May 2005 (n = 189), and June 2005 (n = 235). The prevalence of dairy farms with a within-herd seroprevalence > or = 15% on PEI was 6.4% in May 2004. In May and June 2005, respectively, 10.1% and 10.2% of farms had a > or = 15% within-herd seroprevalence. In 11 farms that were considered positive based on bulk milk samples, blood samples were collected from all adult cows in September 2005, in conjunction with a 4th bulk milk sample on the same day. The correlation coefficient between serology and bulk milk ELISA was 0.87. The results of this study demonstrate that the prevalence of N. caninum in dairy farms can be estimated by using a bulk milk ELISA.

Effect of Neospora caninum-serostatus on culling, reproductive performance and milk production in Dutch dairy herds with and without a history of Neospora caninum-associated abortion epidemics.

We quantified the effect of Neospora caninum (NC)-serostatus on culling and (re)production in 83 herds randomly selected from the Dutch dairy herd population (random group) and in 17 herds that had experienced an abortion epidemic associated with NC infection (epidemic-abortion group). In the random group, a single whole-herd blood sampling was done during the spring of 2003, while in the epidemic-abortion group whole-herd blood sampling was done repeatedly at least once a year starting after the abortion epidemic during the period 1997-2000 until the summer of 2004. Serological test-results for NC were given as 'negative' (N), 'low-positive' (LP) and 'high-positive' (HP). For analysing the time to culling, calving interval and age of first calving, survival analysis was used. For categorical reproduction parameters either a logistic-regression model (abortion, non-return after 1st insemination) or a Poisson-regression model (number of inseminations per pregnancy) was used. For milk production a linear-mixed model was used. All models were controlled, if applicable, for confounding variables like parity, production, season, year and abortion and adjusted for within-herd clustering. In random herds, HP serostatus increased the hazard for culling 1.73-fold (95% CI: 1.37-2.19) compared to N and LP serostatus. Compared to N serostatus, LP and HP serostatus in epidemic-abortion herds increased the odds for abortion 1.88-fold (95% CI: 1.41-2.52) and 1.72-fold (95% CI: 1.38-2.14), respectively. No other reproduction parameters were associated with NC-serostatus in the random or epidemic-abortion herds. We found no effect of serostatus on milk production in the random group. In contrast, milk production of LP and HP serostatus in the epidemic-abortion group was respectively, 0.72kgmilk/day (95% CI: 0.15-1.03) and 0.59kgmilk/day (95% CI: 0.13-1.30), less during the first 100 days of lactation in the first year after the abortion epidemic compared with N serostatus.