Considering equity in priority setting using transmission models: Recommendations and data needs.

OBJECTIVES: Disease transmission models are used in impact assessment and economic evaluations of infectious disease prevention and treatment strategies, prominently so in the COVID-19 response. These models rarely consider dimensions of equity relating to the differential health burden between individuals and groups. We describe concepts and approaches which are useful when considering equity in the priority setting process, and outline the technical choices concerning model structure, outputs, and data requirements needed to use transmission models in analyses of health equity. METHODS: We reviewed the literature on equity concepts and approaches to their application in economic evaluation and undertook a technical consultation on how equity can be incorporated in priority setting for infectious disease control. The technical consultation brought together health economists with an interest in equity-informative economic evaluation, ethicists specialising in public health, mathematical modellers from various disease backgrounds, and representatives of global health funding and technical assistance organisations, to formulate key areas of consensus and recommendations. RESULTS: We provide a series of recommendations for applying the Reference Case for Economic Evaluation in Global Health to infectious disease interventions, comprising guidance on 1) the specification of equity concepts; 2) choice of evaluation framework; 3) model structure; and 4) data needs. We present available conceptual and analytical choices, for example how correlation between different equity- and disease-relevant strata should be considered dependent on available data, and outline how assumptions and data limitations can be reported transparently by noting key factors for consideration. CONCLUSIONS: Current developments in economic evaluations in global health provide a wide range of methodologies to incorporate equity into economic evaluations. Those employing infectious disease models need to use these frameworks more in priority setting to accurately represent health inequities. We provide guidance on the technical approaches to support this goal and ultimately, to achieve more equitable health policies.

The Role of More Sensitive Helminth Diagnostics in Mass Drug Administration Campaigns: Elimination and Health Impacts.

Diagnostics play a crucial role in determining treatment protocols and evaluating success of mass drug administration (MDA) programmes used to control soil-transmitted helminths (STHs). The current diagnostic, Kato-Katz, relies on inexpensive, reusable materials and can be used in the field, but only trained microscopists can read slides. This diagnostic always underestimates the true prevalence of infection, and the accuracy worsens as the true prevalence falls. We investigate how more sensitive diagnostics would impact on the management and life cycle of MDA programmes, including number of mass treatment rounds, health impact, number of unnecessary treatments and probability of elimination. We use an individual-based model of STH transmission within the current World Health Organization (WHO) treatment guidelines which records individual disability-adjusted life years (DALY) lost. We focus on Ascaris lumbricoides due to the availability of high-quality data on existing diagnostics. We show that the effect of improving the sensitivity of diagnostics is principally determined by the precontrol prevalence in the community. Communities at low true prevalence (<30%) and high true prevalence (>70%) do not benefit greatly from improved diagnostics. Communities with intermediate prevalence benefit greatly from increased chemotherapy application, both in terms of reduced DALY loss and increased probability of elimination. Our results suggest that programmes should be extended beyond school-age children, especially in high prevalence communities. Finally, we argue against using apparent or measured prevalence as an uncorrected proxy for true prevalence.

Progress in the Mathematical Modelling of Visceral Leishmaniasis.

The leishmaniases comprise a complex of diseases characterized by clinical outcomes that range from self-limiting to chronic, and disfiguring and stigmatizing to life threatening. Diagnostic methods, treatments, and vector and reservoir control options exist, but deciding the most effective interventions requires a quantitative understanding of the population level infection and disease dynamics. The effectiveness of any set of interventions has to be determined within the context of operational conditions, including economic and political commitment. Mathematical models are the best available tools for studying quantitative systems crossing disciplinary spheres (biology, medicine, economics) within environmental and societal constraints. In 2005, the World Health Assembly and government health ministers of India, Nepal, and Bangladesh signed a Memorandum of Understanding to eliminate the life threatening form of leishmaniasis, visceral leishmaniasis (VL), on the Indian subcontinent by 2015 through a combination of early case detection, improved treatments, and vector control. The elimination target is <1 case/10,000 population at the district or subdistrict level compared to the current 20/10,000 in the regions of highest transmission. Towards this goal, this chapter focuses on mathematical models of VL, and the biology driving those models, to enable realistic predictions of the best combination of interventions. Several key issues will be discussed which have affected previous modelling of VL and the direction future modelling may take. Current understanding of the natural history of disease, immunity (and loss of immunity), and stages of infection and their durations are considered particularly for humans, and also for dogs. Asymptomatic and clinical infection are discussed in the context of their relative roles in Leishmania transmission, as well as key components of the parasite-sandfly-vector interaction and intervention strategies including diagnosis, treatment and vector control. Gaps in current biological knowledge and potential avenues to improve model structures and mathematical predictions are identified. Underpinning the marriage between biology and mathematical modelling, the content of this chapter represents the first step towards developing the next generation of models for VL.

Influence of age, severity of infection, and co-infection on the duration of respiratory syncytial virus (RSV) shedding.

RSV is the most important viral cause of pneumonia and bronchiolitis in children worldwide and has been associated with significant disease burden. With the renewed interest in RSV vaccines, we provide realistic estimates on duration, and influencing factors on RSV shedding which are required to better understand the impact of vaccination on the virus transmission dynamics. The data arise from a prospective study of 47 households (493 individuals) in rural Kenya, followed through a 6-month period of an RSV seasonal outbreak. Deep nasopharyngeal swabs were collected twice each week from all household members, irrespective of symptoms, and tested for RSV by multiplex PCR. The RSV G gene was sequenced. A total of 205 RSV infection episodes were detected in 179 individuals from 40 different households. The infection data were interval censored and assuming a random event time between observations, the average duration of virus shedding was 11·2 (95% confidence interval 10·1-12·3) days. The shedding durations were longer than previous estimates (3·9-7·4 days) based on immunofluorescence antigen detection or viral culture, and were shown to be strongly associated with age, severity of infection, and revealed potential interaction with other respiratory viruses. These findings are key to our understanding of the spread of this important virus and are relevant in the design of control programmes.

Kinetics of the neutralizing antibody response to respiratory syncytial virus infections in a birth cohort.

The kinetics of respiratory syncytial virus (RSV) neutralizing antibodies following birth, primary and secondary infections are poorly defined. The aims of the study were to measure and compare neutralizing antibody responses at different time points in a birth cohort followed-up over three RSV epidemics. Rural Kenyan children, recruited at birth between 2002 and 2003, were monitored for RSV infection over three epidemic seasons. Cord and 3-monthly sera, and acute and convalescent sera following RSV infection, were assayed in 28 children by plaque reduction neutralization test (PRNT). Relative to the neutralizing antibody titers of pre-exposure control sera (1.8 log10 PRNT), antibody titers following primary infection were (i) no different in sera collected between 0 and 0.4 months post-infection (1.9 log10 PRNT, P=0.146), (ii) higher in sera collected between 0.5 and 0.9 (2.8 log10 PRNT, P<0.0001), 1.0-1.9 (2.5 log10 PRNT, P<0.0001), and 2.0-2.9 (2.3 log10 PRNT, P<0.001) months post-infection, and (iii) no different in sera collected at between 3.0 and 3.9 months post-infection (2.0 log10 PRNT, P=0.052). The early serum neutralizing response to secondary infection (3.02 log10 PRNT) was significantly greater than the early primary response (1.9 log10 PRNT, P<0.0001). Variation in population-level virus transmission corresponded with changes in the mean cohort-level neutralizing titers. It is concluded that following primary RSV infection the neutralizing antibody response declines to pre-infection levels rapidly (~3 months) which may facilitate repeat infection. The kinetics of the aggregate levels of acquired antibody reflect seasonal RSV occurrence, age, and infection history.

The interaction of host genetics and disease processes in chronic livestock disease: a simulation model of ovine footrot.

A stochastic, individual-based, simulation model of footrot in a flock of 200 ewes was developed that included flock demography, disease processes, host genetic variation for traits influencing infection and disease processes, and bacterial contamination of the environment. Sensitivity analyses were performed using ANOVA to examine the contribution of unknown parameters to outcome variation. The infection rate and bacterial death rate were the most significant factors determining the observed prevalence of footrot, as well as the heritability of resistance. The dominance of infection parameters in determining outcomes implies that observational data cannot be used to accurately estimate the strength of genetic control of underlying traits describing the infection process, i.e. resistance. Further work will allow us to address the potential for genetic selection to control ovine footrot.

The natural history of respiratory syncytial virus in a birth cohort: the influence of age and previous infection on reinfection and disease.

This study aimed to quantify the effect of age, time since last infection, and infection history on the rate of respiratory syncytial virus infection and the effect of age and infection history on the risk of respiratory syncytial virus disease. A birth cohort of 635 children in Kilifi, Kenya, was monitored for respiratory syncytial virus infections from January 31, 2002, to April 22, 2005. Predictors of infection were examined by Cox regression and disease risk by binomial regression. A total of 598 respiratory syncytial virus infections were identified (411 primary, 187 repeat), with 409 determined by antigen assay and 189 by antibody alone (using a "most pragmatic" serologic definition). The incidence decreased by 70% following a primary infection (adjusted hazard ratio = 0.30, 95% confidence interval: 0.21, 0.42; P < 0.001) and by 59% following a secondary infection (hazard ratio = 0.41, 95% confidence interval: 0.22, 0.73; P = 0.003), for a period lasting 6 months. Relative to the age group <6 months, all ages exhibited a higher incidence of infection. A lower risk of severe disease following infection was independently associated with increasing age (P < 0.001) but not reinfection. In conclusion, observed respiratory syncytial virus incidence was lowest in the first 6 months of life, immunity to reinfection was partial and short lived, and disease risk was age related.

Persistence of the efficacy of copper oxide wire particles against Haemonchus contortus in grazing South African goats.

A study was conducted to examine the duration of anthelmintic effect of copper oxide wire particles (COWP) in grazing goats, as data for the persistence of efficacy of COWP in this host species is limited. Forty-eight indigenous male goats were infected naturally by grazing them on Haemonchus contortus-infected pasture. When the faecal egg count (FEC) in the goats was 3179 ± 540 eggs per gram of faeces (mean ± standard error), half the animals were treated with 4 g COWP (day 0; mean live weight=25.5 ± 0.8 kg). Eight treated (COWP) and eight non-treated (CONTROL) goats were removed from the pasture on each of days 7, 28 and 56, maintained for 27 or 29 days in concrete pens and then humanely slaughtered for nematode recovery. Mean liver copper levels were in the high range in the goats removed from pasture at day 7 (treated: 191 ± 19.7 ppm; untreated: 120 ± 19.7 ppm; P=0.022), but had dropped to normal levels at days 28 and 56. The mean H. contortus burdens of the treated versus the non-treated goats were, respectively, 184 ± 48 and 645 ± 152 for the goats removed from pasture at day 7 (71% reduction; P=0.004), 207 ± 42 and 331 ± 156 at day 28 (37% reduction; P=0.945) and 336 ± 89 and 225 ± 53 at day 56 (-49% reduction; P=0.665). Weekly monitoring of FECs after treatment until slaughter indicated that the COWP-treated goats had lower FECs than the controls, the treatment main effect being significant at days 7, 28 and 56 (P<0.01). The day main effect and the treatment × day interaction were only significant for the goats removed from pasture at day 28 (P ≤ 0.001). Packed cell volumes increased during the course of the experiment (day, P<0.001), but the treatment main effect was significant only for the goats removed from pasture at day 28 (CONTROL 28 d, 28.65 ± 0.52%

Patterns of delayed detection and persistence of bovine tuberculosis in confirmed and unconfirmed herd breakdowns in cattle and cattle herds in Great Britain.

Approximately 1500/6000 cattle farms that were depopulated during the foot and mouth epidemic in GB in 2001 had been repopulated and subjected to two unrestricted (herd considered free from bovine tuberculosis (bTB)) herd tests. Factors associated with herd breakdown(s) (HBD) and individual cattle reactor status at the second test were investigated. There were 96 HBD in total, with a 3-fold increased risk of HBD in herds that had had a HBD at the first test after restocking. Two mixed effect models were used to investigate factors associated with 324/246,060 reactor cattle at the second bTB test; 228 reactors were at confirmed HBD and 96 at unconfirmed HBD; 253 (79%) reactors at the second test were present and test negative at the first test. In confirmed HBD, the odds of cattle reacting were higher if the restocked farm had a history of bTB before 2001 and if the source and restocked farms were high frequency tested (HFT) farms (routine bTB tests at ≥1 per 2 years). Reacting cattle were more likely to have been born on the restocked farm before the first test after FMD and less likely to have been purchased from a low frequency tested (LFT) farm (routine bTB tests at 3-4 year intervals) after the first test compared with a baseline of cattle purchased from a LFT farm before the first test. Unconfirmed HBD at the second test was more likely when the first test was a confirmed HBD and when there was a history of bTB in the restocked farm. In contrast to confirmed HBD, cattle purchased from a LFT farm after the first test were at increased risk of reacting at an unconfirmed HBD at the second test. We conclude that a farm history of bTB suggests persistence of bTB on the farm. Confirmed tests indicate exposure to bTB for some time indicated by the increased risk from HFT source and restocked farms and a farm history of bTB. The risks for reactors are related to the farm and herd and duration of exposure to these risks. Therefore, the spread of bTB to naïve herds would be reduced if farmers only introduced cattle known not to have been in herds and on farms exposed to bTB. Management of bTB on farms with bTB is complicated because there is undisclosed infection in cattle and environmental contamination.

Modelling the transmission dynamics of Theileria annulata: model structure and validation for the Turkish context.

A mathematical model that describes the transmission dynamics of Theileria annulata is proposed that consists of 2 host components: the Hyalomma tick population and a compartmental model of T. annulata infection in the cattle population. The model was parameterized using data describing tick infestation and the infection status of cattle in Turkey from 2006 to 2008. The tick attachment rates are highly seasonal and because of the temporal separation of infectious and susceptible ticks virtually all ticks are infected by carrier cattle, so that annual peaks of disease in cattle do not impact on infection in the Hyalomma tick population. The impact of intervention measures that target the tick population both on the host and in the environment and their impact on the transmission of T. annulata were investigated. Interventions that have a limited 'one-off' impact and interventions that have a more permanent impact were both considered. The results from the model show the importance of targeting ticks during the period when they have left their first host as nymphs but have yet to feed on their second host.

A meta-analysis of the effect of dose and age at exposure on shedding of Mycobacterium avium subspecies paratuberculosis (MAP) in experimentally infected calves and cows.

A meta-analysis was performed using all published and one unpublished long-term infection-challenge experiments to quantify the age- and dose-dependence of early and late shedding of Mycobacterium avium subsp. paratuberculosis (MAP) in cattle. There were 194 animals from 17 studies that fulfilled the inclusion criteria, of which 173 received a known dose of MAP and 21 were exposed naturally. Results from parametric time-to-event models indicated that challenging older calves or using multiple-exposure experimental systems resulted in a smaller proportion and shorter duration of early shedding as well as slower transition to late shedding from latent compartments. Calves exposed naturally showed variable infection progression rates, not dissimilar to other infection routes. The log-normal distribution was most appropriate for modelling infection-progression events. The infection pattern revealed by the modelling allowed better understanding of low-grade endemicity of MAP in cattle, and the parameter estimates are the basis for future transmission dynamics modelling.

Tactical treatment with copper oxide wire particles and symptomatic levamisole treatment using the FAMACHA(©) system in indigenous goats in South Africa.

Haemonchosis is considered to be the most economically important gastrointestinal disease of small ruminants in the tropics and subtropics. However, chemical anthelmintics, which were the mainstay of control, have been compromised by a high prevalence of resistance worldwide. Copper oxide wire particles (COWP) have been shown to have anthelmintic effects, but few studies have examined their use under field conditions. The use of COWP was therefore evaluated as a tactical anthelmintic treatment in indigenous goats raised under communal farming conditions in Bergville, KwaZulu-Natal Province, South Africa. At the beginning of the summer rainfall season (October 2007), the faecal egg counts of 172 female goats belonging to 15 farmers were determined and this sampling continued every four weeks until the second week of January 2008. The goats within each of the 15 herds were ranked according to their faecal egg counts for this week. The goats were sequentially paired off within each ranking starting with those goats with the highest counts. One goat from each pair was randomly allocated to a treated or control group. Two weeks later, a 4 g COWP bolus was randomly administered to each goat in the treated group. Faecal egg counts were carried out on the goats two weeks following treatment, and the sampling of the goats then proceeded every four weeks until October 2008. Except for the six-week period prior to the administration of the COWP, the goats were examined according to the FAMACHA(©) system and symptomatically treated with 12 mg/kg levamisole when anaemic. The percentage reduction in faecal egg count due to the COWP treatment was 89.0%. Mean pre- and post-treatment faecal egg counts for the COWP-treated group (n=73) were 2347 eggs per gram of faeces (epg) and 264 epg, respectively. The corresponding values for the untreated controls (n=66) were 2652 epg and 2709 epg. The prevalence of Haemonchus spp. larvae in pre- and post-treatment faecal cultures was 72% and 46%, respectively. Symptomatic anthelmintic treatments in combination with mid-summer tactical treatments with COWP appear to be useful strategies for the control of Haemonchus contortus in indigenous goats in this farming system and this approach could have application in other similar agro-ecological zones.

Factors associated with changes of state of foot conformation and lameness in a flock of sheep.

The aim of this research was to investigate transitions between foot conformation, lameness and footrot in sheep. Data came from one lowland flock of approximately 700 ewes studied for 18 months. Multilevel multistate analyses of transitions between good and poor foot conformation states in ewes, and lame and non-lame states in ewes and lambs were conducted. Key results were that the longer sheep had feet in good conformation, the more likely they were to stay in this state; similarly, the longer a ewe was not lame the more likely she was not to become lame. Ewes with poor foot conformation were more likely to become lame (OR: 1.83 (1.24-2.67)) and to be >4 years (OR: 1.50 (1.09-2.05)). Ewes with footrot were less likely to move to good foot conformation (OR: 0.48 (0.31-0.75)) and were more likely to become lame (OR: 3.81 (2.60-5.59)). Ewes lame for >4 days and not treated with parenteral antibacterials had a higher risk of developing (OR: 2.00 (1-3.61)), or remaining in (OR: 0.49 (0.29-0.95)), poor foot conformation compared with ewes never lame. Treatment of ewes lame with footrot with parenteral antibacterials increased the probability of transition from a lame to a non-lame state (OR: 1.46 (1.05-2.02)) and these ewes, even if lame for >4 days, were not more likely to develop poor foot conformation. The risk of a ewe becoming lame increased when at least one of her offspring was lame (OR: 2.03 (1.42-2.92)) and when the prevalence of lameness in the group was ≥5% (OR: 1.42 (1.06-1.92)). Lambs were at increased risk of becoming lame when they were male (OR: 1.42 (1.01-2.01)), single (OR: 1.86 (1.34-2.59)) or had a lame dam or sibling (OR: 3.10 (1.81-5.32)). There were no explanatory variables associated with lambs recovering from lameness. We conclude that poor foot conformation in ewes increases the susceptibility of ewes to become lame and that this can arise from untreated footrot. Treatment of ewes lame with footrot with parenteral antibacterials leads to recovery from lameness and prevents or resolves poor foot conformation which then reduces the susceptibility to further lameness with footrot.

A cohort study of post-weaning multisystemic wasting syndrome and PCV2 in 178 pigs from birth to 14 weeks on a single farm in England.

Our hypothesis was that pigs that develop post-weaning multisystemic wasting syndrome (PMWS) are detectable from an early age with signs of weight loss and other clinical and serological abnormalities. Therefore, the objective of this study was to investigate the temporally varying and fixed events linked with the clinical incidence of PMWS by comparing affected and unaffected pigs in a cohort of 178 male piglets. Piglets were enrolled at birth and examined each week. Samples of blood were collected at regular intervals. The exposures measured were porcine circovirus type 2 (PCV2) antibody titres in all 178 and PCV2 antigen in a subset of 75 piglets. We also observed piglet health and measured their weight, and a post-mortem examination was performed by an external laboratory on all pigs between 6 and 14 weeks of age that died. From the cohort, 14 (8%) pigs died from PMWS and 4% from other causes. A further 37 pigs between 6 and 14 weeks of age died from PMWS (30) and ileitis and other causes (7). PMWS was only apparent in pigs from 1 to 2 weeks before death when they wasted rapidly. There were no other characteristic clinical signs and no obvious gross clinical lesions post-mortem. There was no strong link with PCV2 antibody throughout life but PCV2 antigen level was higher from 4 to 6 weeks of age in pigs that died from PMWS compared with pigs that died from other causes.

Risk factors for herd breakdown with bovine tuberculosis in 148 cattle herds in the south west of England.

Bovine tuberculosis (bTB) is caused by Mycobacterium bovis. The disease has a long latent period, heterogenous spread, can infect many species and can persist in the environment. In the UK, the rate of herd breakdowns (HBD) with bTB is increasing. A retrospective cohort study of 148 cattle herds was set up to investigate risk factors for HBD from October 2001 to November 2004. Herds were selected from farms located in the randomised badger culling trial (RBCT) and comprised holdings (24%) that were restocked with cattle after the foot and mouth disease (FMD) epidemic in 2001 and holdings (76%) that were continuously stocked throughout the FMD epidemic. Farmers were interviewed between June 2003 and February 2004. Questions on herd and farm management were asked for the period October 2001 to June 2003. Data on herd testing for bTB were sourced from the VetNet database and historic data from 1995 were used in the analysis. A discrete time survival analysis was used to examine factors associated with the risk of HBD. By the end of the study period, November 2004, 50% of study herds had experienced a HBD with bTB at least once. Farms that were restocked for less than 1 year after FMD had a reduced risk of HBD (P<0.01) compared with continuously stocked farms in the same year. This reduced risk did not persist after 1 year of restocking. Feeding vitamin and mineral lick supplements compared with not feeding these supplements also reduced the risk of HBD. Factors associated with an increased risk of HBD were storing manure and slurry indoors or in a closed container, spreading manure all year round, herds with dairy cattle compared with herds without dairy cattle, increasing herd size, purchase of cattle from markets, location of the farm in the proactive area of the RBCT compared with survey only and location of farms in Somerset and North Devon. The lower risk of HBD in the first year after restocking but not the second or third year suggests that removal of all cattle might have lowered the infectious load of M. bovis on these premises for a period of time but that this did not persist once cattle were reintroduced. Purchase of cattle from markets suggests that there was a risk of introduction or re-introduction of bTB from these cattle. Method of storage or lack of storage of slurry might aid persistence of M. bovis in the environment if M. bovis survives in slurry in some circumstances.

The control of Corynebacterium pseudotuberculosis infection in sheep flocks: a mathematical model of the impact of vaccination, serological testing, clinical examination and lancing of abscesses.

A mathematical model of Corynebacterium pseudotuberculosis infection in sheep flocks was used to evaluate strategies for control and elimination of caseous lymphadenitis (CLA). Control strategies tested were vaccination, serological testing and removal of seropositives, clinical examination and removal of sheep with abscesses, lancing abscesses, and appropriate combinations. Three different infection rates with and without replacement of culled ewes were used to evaluate the control options. Controls were either implemented immediately after infection was detected in a flock or once CLA was at endemic equilibrium, and with different frequencies of examination or testing. Elimination of infection was defined as 99% confidence that no sheep were infected with C. pseudotuberculosis. The control strategies were evaluated by estimating the reduction in infection or probability of elimination and the number of ewes culled from the flock. Lancing abscesses reduced the prevalence of infection when the initial prevalence was <0.60, but elimination was unlikely. A vaccine efficacy of 0.79 or more led to elimination of infection from the flock, provided that the endemic prevalence of infection was <0.60. A combination of vaccination and clinical examination reduced the prevalence of infection at a faster rate than using clinical examination or vaccination alone where five rounds of clinical examination were done. Serological testing led to elimination of infection after five tests, but was highly dependent upon the diagnostic test sensitivity and specificity and management options used: a test sensitivity of 0.90 always resulted in elimination. A test specificity greater than 0.90 prevented removal of many false positive ewes and consequently prevented a large reduction in lamb production. Elimination was most likely using a serological test with sensitivity and specificity >0.90, but vaccination combined with clinical examination reduced infection rapidly with little impact on lamb productivity. Further research is required to develop a diagnostic test with at least 0.90 specificity and sensitivity under field conditions before any methods of control can be recommended with confidence.

A stochastic mathematical model of the within-herd transmission dynamics of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): fade-out and persistence.

A stochastic, mathematical model of a farrow-finish pig herd was developed and used to investigate the within-herd transmission dynamics of PRRSV, and to examine patterns of on-farm persistence and fade-out. The model was structured to represent the management of a typical European pig herd. Three parameters determining the natural history of infection were derived from the literature. Transmission parameters were chosen using PRRSV antibody data from a cross-sectional study of 103 pig herds (Evans et al., 2008). The seroprevalence by age was generated from the model at 21-day intervals and was compared to the cross-sectional field data using log-likelihood, accounting for the accuracy of the ELISA test used. The model was run for various isolation practices of purchased gilts, contact structure, herd size and the frequency of re-introduction of infectious gilts. The time-dependent log-likelihood patterns varied between herds in a similar way to patterns observed from serological values from the 103 farms. Essentially they indicated two patterns of seroprevalence: herds in which PRRSV was stably persistent, and herds in which PRRSV was unstable, either recently introduced or recently faded-out. With a herd size of 327 sows with identical management, fade-out of virus occurred within 4 weeks in 21.9% of simulations. Without isolation of gilts from sows, fade-out within 250 days decreased from 81.6% to 14.3% and for herd sizes of 75, 150, 300 and 600, the probability of persistence of virus for >1200 days was 4%, 13.4%, 20.4% and 18.2%, respectively. Introduction of virus at a rate of approximately 0.37 times per year resulted in virus persisting for >1200 days in 32.4% of simulations, compared with 17.6% for no re-introduction. Fade-out of virus was most likely to occur within breeding females before virus reached young stock. Persistence was more likely once PRRSV was present in piglets which in turn infected rearing-pigs. The probability of persistence was higher with increased herd size, increased contact between different age groups and increased re-introduction of infectious gilts. The ability of the model to capture the variability in cross-sectional, age-related serological patterns suggests that the processes of re-introduction, persistence and fade-out of PRRSV play critical roles in PRRSV epidemiology. The potential importance to pig production and transmission of virus between herds is discussed.

Herd and individual animal risks associated with bovine tuberculosis skin test positivity in cattle in herds in south west England.

The aim of this study was to investigate the cattle-exposure factors associated with the risk of a bovine animal reacting to a bovine tuberculosis (bTB) skin test at a whole herd test. There were 148 study farms enrolled. These were located in six counties of the south west of England in an area considered endemic for bovine tuberculosis (bTB): 24% were restocked after foot and mouth disease (FMD) in 2001; all farms were located within the Randomised Badger Culling Trial (RBCT) area. Data on cattle on these farms were sourced from the bTB Vetnet database from 1996 to 2004 and from the British Cattle Movement Scheme database. Individual animal records were created that included data on whether or not an animal became a reactor at a full-herd bTB test between 1 June 2001 and 19 August 2004, their prior exposure to cattle with bTB (defined by presence at a bTB test where at least one reactor was detected), whether the animal was homebred, the farm history of bTB and the farm restocking status. Data from 144 farms were used, 4 farms had no data. Cattle were more likely to react to the bTB skin test when they had been present at a previous bTB herd test (or tests) where other cattle had reacted to the skin test. This positively correlated with age and the number of bTB tests an animal had had. Cattle on restocked farms were less likely to react to the skin test compared with cattle on continuously stocked farms. These results highlight the likely importance of exposure to infected cattle at a previous test as a source of infection to cattle that subsequently became reactors and suggest that there was a lower risk of exposure to bTB to cattle in newly formed herds.

Bayesian analysis of a mastitis control plan to investigate the influence of veterinary prior beliefs on clinical interpretation.

The fundamental objective for health research is to determine whether changes should be made to clinical decisions. Decisions made by veterinary surgeons in the light of new research evidence are known to be influenced by their prior beliefs, especially their initial opinions about the plausibility of possible results. In this paper, clinical trial results for a bovine mastitis control plan were evaluated within a Bayesian context, to incorporate a community of prior distributions that represented a spectrum of clinical prior beliefs. The aim was to quantify the effect of veterinary surgeons' initial viewpoints on the interpretation of the trial results. A Bayesian analysis was conducted using Markov chain Monte Carlo procedures. Stochastic models included a financial cost attributed to a change in clinical mastitis following implementation of the control plan. Prior distributions were incorporated that covered a realistic range of possible clinical viewpoints, including scepticism, enthusiasm and uncertainty. Posterior distributions revealed important differences in the financial gain that clinicians with different starting viewpoints would anticipate from the mastitis control plan, given the actual research results. For example, a severe skeptic would ascribe a probability of 0.50 for a return of < 5 UK pounds per cow in an average herd that implemented the plan, whereas an enthusiast would ascribe this probability for a return of > 20 UK pounds per cow. Simulations using increased trial sizes indicated that if the original study was four times as large, an initial skeptic would be more convinced about the efficacy of the control plan but would still anticipate less financial return than an initial enthusiast would anticipate after the original study. In conclusion, it is possible to estimate how clinicians' prior beliefs influence their interpretation of research evidence. Further research on the extent to which different interpretations of evidence result in changes to clinical practice would be worthwhile.