Low accuracy of Bayesian latent class analysis for estimation of herd-level true prevalence under certain disease characteristics—An analysis using simulated data

Estimation of the true prevalence of infected individuals involves the application of a diagnostic test to a population and adjusting according to test performance, sensitivity and specificity. Bayesian latent class analysis for the estimation of herd and animal-level true prevalence, has become increasingly used in veterinary epidemiology and is particularly useful in incorporating uncertainty and variability into analyses in a flexible framework. However, the approach has not yet been evaluated using simulated data where the true prevalence is known. Furthermore, using this approach, the within-herd true prevalence is often assumed to follow a beta distribution, the parameters of which may be modelled using hyperpriors to incorporate both uncertainty and variability associated with this parameter. Recently however, the authors of the current study highlighted a potential issue with this approach, in particular, with fitting the distributions and a tendency for the resulting distribution to invert and become clustered at zero. Therefore, the objective of the present study was to evaluate commonly specified models using simulated datasets where the herd-level true prevalence was known. The specific purpose was to compare findings from models using hyperpriors to those using a simple beta distribution to model within-herd prevalence. A second objective was to investigate sources of error by varying characteristics of the simulated dataset. Mycobacterium avium subspecies paratuberculosis infection was used as an example for the baseline dataset. Data were simulated for 1000 herds across a range of herd-level true prevalence scenarios, and models were fitted using priors from recently published studies. The results demonstrated poor performance of these latent class models for diseases characterised by poor diagnostic test sensitivity and low within-herd true prevalence. All variations of the model appeared to be sensitive to the prior and tended to overestimate herd-level true prevalence. Estimates were substantially improved in different infection scenarios by increasing test sensitivity and within-herd true prevalence. The results of this study raise questions about the accuracy of published estimates for the herd-level true prevalence of paratuberculosis based on serological testing, using latent class analysis. This study highlights the importance of conducting more rigorous sensitivity analyses than have been carried out in previous analyses published to date

Control of paratuberculosis: who, why and how. A review of 48 countries

Paratuberculosis, a chronic disease affecting ruminant livestock, is caused by Mycobacterium avium subsp. paratuberculosis (MAP). It has direct and indirect economic costs, impacts animal welfare and arouses public health concerns. In a survey of 48 countries we found paratuberculosis to be very common in livestock. In about half the countries more than 20% of herds and flocks were infected with MAP. Most countries had large ruminant populations (millions), several types of farmed ruminants, multiple husbandry systems and tens of thousands of individual farms, creating challenges for disease control. In addition, numerous species of free-living wildlife were infected. Paratuberculosis was notifiable in most countries, but formal control programs were present in only 22 countries. Generally, these were the more highly developed countries with advanced veterinary services. Of the countries without a formal control program for paratuberculosis, 76% were in South and Central America, Asia and Africa while 20% were in Europe. Control programs were justified most commonly on animal health grounds, but protecting market access and public health were other factors. Prevalence reduction was the major objective in most countries, but Norway and Sweden aimed to eradicate the disease, so surveillance and response were their major objectives. Government funding was involved in about two thirds of countries, but operations tended to be funded by farmers and their organizations and not by government alone. The majority of countries (60%) had voluntary control programs. Generally, programs were supported by incentives for joining, financial compensation and/or penalties for non-participation. Performance indicators, structure, leadership, practices and tools used in control programs are also presented. Securing funding for long-term control activities was a widespread problem. Control programs were reported to be successful in 16 (73%) of the 22 countries. Recommendations are made for future control programs, including a primary goal of establishing an international code for paratuberculosis, leading to universal acknowledgment of the principles and methods of control in relation to endemic and transboundary disease. An holistic approach across all ruminant livestock industries and long-term commitment is required for control of paratuberculosis

Epidemiology of Mycobacterium avium subspecies paratuberculosis infection on sheep, beef cattle and deer farms in New Zealand : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Massey University, Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand

Paratuberculosis (Ptb) is a chronic enteric infection caused by Mycobacterium avium subspecies paratuberculosis (MAP), affecting wild and domestic ruminants. In domestic ruminants MAP infection is largely sub-clinical, but can result in chronic diarrhoea leading to emaciation and death. Clinical disease is commonly observed in adult cattle and sheep but in deer the disease incidence is higher in young animals (8-12 months). In the New Zealand pastoral farming system, it is common practice to co-graze Ptb susceptible livestock species (sheep, cattle, and deer) together, either concurrently or successively, on the same pasture. Thus several susceptible species have contact at farm level, being at risk of transmitting MAP between species through contaminated pasture. Johne’s Disease Research Consortium (JDRC), a partnership between livestock industries, government and research providers was created to study Ptb in an overarching approach, involving all susceptible species, aiming to generate scientific knowledge to support Ptb control policies. The present research was implemented under the financial support of JDRC, aiming to generate epidemiological information about Ptb infection and clinical disease on mixedspecies pastoral farms, grazing sheep, beef cattle, and/or deer. A total of 350 mixedspecies farms (11,089 animals) were faecal and blood sampled and related epidemiological information was collected. Data was used to estimate: i) the national herd level true prevalence (HTP) of MAP infection on sheep, beef cattle and deer, ii) the risk of MAP infection and clinical disease incidence associated with species co-grazing,iii) the association between infected and affected herds/flocks and production outputs, and iv) relationships between molecular strain types of MAP isolates and their distribution across livestock sectors and geographical areas. Finally, data and results from previous studies allowed v) the development and calibration of a two host-species (sheep & beef cattle) mathematical model, simulating MAP transmission between species and the effect of several control measures under mixed species farming. MAP infection is widely spread in New Zealand. A Bayesian analysis to account for lack of sensitivity (Se) and specificity (Sp) of testing protocols, indicated that the highest HTP estimate for sheep flocks (75%, posterior probability interval (PPI) 68- 82%), followed by deer (46%, PPI 39-54%) and beef herds (43%, PPI 359-51%). Sheep and beef cattle flocks/herds presented a higher prevalence in the North Island (NI), whereas deer infection was mainly located in the South Island (SI). Logistic and Poisson regression models using Bayesian inference to adjust for lack of Se and Sp of diagnostic tests and of farmer’s recall of clinical Ptb indicated that the shared use of pasture was associated with Ptb prevalence and incidence. When beef cattle and sheep were co-grazed, the infection risk increased 3-4 times in each species. Similarly, co-grazing of beef cattle and deer increased 3 times the risk of infection on deer. Co-grazing beef cattle with sheep, or beef cattle with deer, also was associated with increased clinical incidence in these species. Conversely, the co-grazing of sheep and deer was associated with a lower clinical disease incidence in both species. Classical logistic and Poisson regression models indicated that MAP ‘infection’ status was significantly (p =0.03) associated with reduced calving rates in beef cattle herds and lower culling rates in deer herds and sheep flocks. Moreover, in sheep flocks and deer herds, a significant and a marginally significant (p = 0.05 and 0.09, respectively)Molecular analysis of MAP isolates obtained from sheep, cattle (beef and dairy) and deer, using a combination of the variable number of tandem repeats (VNTR) method and the short sequence repeat (SSR) method, rendered 17 MAP subtypes. Analysis indicated significantly higher subtype richness in dairy cattle and livestock sector as the main source of subtype variation. Moreover, similar subtypes were sourced from sheep and beef cattle, which tended to be different to the ones obtained from other livestock sectors. However, when beef cattle and deer were both present on the same farm, they harboured similar subtypes. These results provided strong evidence for transmission of MAP between species through the joint use of pasture. Simulation results of a mathematical infectious disease model for Ptb indicated that the length of the co-grazing period was positively associated with the infection prevalence of sheep and beef cattle. Long pasture spelling periods from 9 to 15 months reduced MAP contamination up to 99%. However, the infection of naïve animals was still possible, but the prevalence remained <1% for at least 25 years. The simultaneous application of control measures on both species was the most efficient approach to reduce the prevalence and incidence. The separation of co-grazed species in tandem with an increased farmer surveillance, to reduce the time that clinical animals remained on the farm, was most effective in sheep, whereas T&C was in beef cattle. The present research provides evidence that MAP infection is highly endemic in New Zealand farming livestock, and that the clinical disease incidence is generally low (<0.5%) in most infected farms. Moreover, inference from molecular pathogen typing of strategically collected isolates from farms across New Zealand strongly suggested that MAP is transmitted between species, mainly from sheep to beef cattle and between beef cattle and deer, all of which are commonly grazed together in the New Zealand pastoral farming system

Optimal drug control under risk of drug resistance – The case of African animal trypanosomosis

We examine two widely used treatment strategies for African animal trypanosomosis in West Africa: preventive drug control ex-ante trypanosomosis infection and curative drug control ex-post trypanosomosis infection. We investigate which combination of these alternative strategies is economically optimal for cattle farmers. We apply a dynamic optimisation framework to consider both the negative externality of drug resistance development and human behaviour. We develop a bio-economic model to simulate the economic consequences of treatment strategies in a dynamic scenario that takes into account the interactions among the vector, host and livestock farmers. This model allows for the evolution of drug-resistant trypanosomes through trypanocide misuse and simulates the observed behaviours of cattle farmers based on the elicited risk and time preferences of a sample of 202 cattle farmers in Mali and Burkina Faso. The results show that the private optimal mix of treatment strategies for a risk averse and patient farmer involves preventive treatment for susceptible cattle, supported by a small number of curative treatments for infected cattle. Compared with the treatment strategies observed in the field, this optimal mix of treatment strategies would save approximately 5% of the annual income of a livestock farmer in the study area and would reduce the prevalence of trypanosomosis. In addition, we demonstrate that a reduction in a farmer's risk aversion is associated with higher treatment rates that can avoid additional losses. By contrast, a decrease in a farmer's patience is related to lower treatment rates that thwart additional benefits. Our results suggest that individual risk and time preferences need to be considered in the development process of disease control interventions

Prevalence of tuberculosis, brucellosis and trypanosomiasis in cattle in Tanzania: a systematic review and meta-analysis

A meta-analysis was performed to derive prevalence estimates for Brucella spp., Mycobacterium spp. and Trypanosoma spp. in cattle in Tanzania using data derived from a systematic review of zoonotic hazards in cattle production systems. Articles published before 2012 reporting prevalence and considered at least moderate in quality were included in the analysis. Results showed high heterogeneity between studies, with wide ranges in the reported prevalence: Brucella (0.3–60.8%), Mycobacterium (0.1–13.2%) and Trypanosoma (0.82–33.3%). Overall meta-analytic mean prevalence estimates were 8.2% (95% CI 6.5–10.2), 1.28% (95% CI 0.35–4.58) and 10.3% (95% CI 6.20–16.70) respectively, for Brucella spp., Mycobacterium spp. and Trypanosoma spp. Time and region were predictors of variability of Brucella spp. prevalence, while diagnostic test was a strong predictor of Mycobacterium spp. prevalence, with higher prevalence estimates given by skin tests compared with post-mortem inspection. None of the studied factors were associated with prevalence of Trypanosoma spp. The small sample sizes, range of study locations, study designs and diagnostics used, contributed to high variability among prevalence estimates. Larger and more robust prevalence studies are needed to adequately support risk assessment and management of animal and public health threats