Evaluation of surveillance strategies for bovine tuberculosis (Mycobacterium bovis) using an individual based epidemiological model

The Netherlands holds the bovine tuberculosis-free (BTB-free) status according to European Union standards, but in recent years small outbreaks of the infection have occurred. After the last outbreak in 1999 with 10 infected herds the question raised if the current surveillance system, visual inspection of carcasses at the slaughterhouse, is efficient enough to detect infected cattle in time and to maintain the official BTB-free status.

Through epidemiological modelling, the risk of a major outbreak is quantified, using one of six surveillance strategies. These are the currently used visual inspection of carcasses at the slaughterhouse (SL), the ELISA test on blood samples of carcasses at the slaughterhouse (ELISA-B), the γ-interferon test on blood samples of carcasses at the slaughterhouse (GAMMA-B), comparative tuberculination of the herd (CT), the combined method of single and comparative tuberculination of the herd (ST + CT) and the ELISA test on samples of bulk milk (ELISA-M). Test frequency of the last three methods was varied as well.

A stochastic individual based model (IBM) was developed to simulate a chain of infected herds, where each individual animal is followed in time. The model mimics the nation-wide situation after the introduction of one infected animal into one herd. BTB-transmission is simulated with an S-E₁-E₂-I state transition model. Output is time until detection of the infection, prevalence in the detected herd and the number of infected herds at the time of detection. For the assessment 500 simulations were used, representing 500 BTB-introductions. Model robustness to parameter values was analysed with Monte Carlo elasticity analysis, for which 1000 simulations were used.

Results of median time until detection and median number of infected farms at detection for SL (302 weeks and seven farms) were in agreement with estimates from an outbreak in the Netherlands in 1999. ELISA-B and GAMMA-B performed better than SL with a much lower median time until detection (189 and 97 weeks, respectively). The results for the tuberculination methods (ST + CT and CT) and ELISA-M depended heavily on the frequency in which the tests were performed. The tuberculination methods ST + CT and CT yield comparable results and detect the infection sooner than SL, also at the lowest tested frequency of once in 5 years. ELISA-M is comparable with SL at frequencies of once in 4 or 5 years, and this test works well at frequencies of once a year or higher. Our study results are used for an economical optimisation analysis of the six surveillance strategies.     

Estimating herd prevalence of bovine brucellosis in 46 USA states using slaughter surveillance

Making valid inferences about herd prevalence from data collected at slaughter is difficult because the observed sample is dependent on the number of animals sampled from each herd, which varies with herd size and culling practices, and the probability of a positive test result, which depends on variable within-herd prevalence levels as well as test sensitivity and specificity. In this study, brucellosis herd prevalence among beef cow-calf operations is estimated from slaughter surveillance data using a method that combines process modeling with Bayesian inference. Inferences are made for two populations; the first population comprises cow-calf beef herds in a typical U.S. state. The second population represents all beef herds in a collection of 46 low-risk states. The Bayesian Monte Carlo method used in this study links process model inputs to observed surveillance results via Bayes Theorem. The surveillance evidence across multiple years is accumulated at a discounted rate based on the probability of introducing new infection into an area. The process model's inputs include herd size, culling rate per herd, within-herd prevalence, serologic test performance, and the probability of successfully investigating positive results. The surveillance results comprise the number of cows and bulls tested at slaughter and the number of affected herds detected each year. The results find at least 95% confidence that brucellosis herd prevalence among beef cow-calf herds is less than 0.014% (3 per 21,500 herds) and 0.00081% (5 per 6,15,770) after 5 years of slaughter surveillance (with no detections of affected herds) in a typical U.S. state and across 46 low-risk U.S. states, respectively. These results were based on conservative modeling assumptions, but sensitivity analysis suggests only slight changes in the results from changing the assumed process model input values. The most influential analytic input was the probability of introducing new infection into a putatively brucellosis-free state or group of states.     

Monte Carlo simulation of surveillance strategies for scrapie in Norwegian sheep

Our aim was to compare the efficiency of different surveillance strategies for detecting scrapie-infected sheep flocks in the Norwegian population using simulation modelling.The dynamic Monte Carlo simulation model has the flock as the unit. The input parameters include properties of the sheep population (number of flocks, flock size, age distribution, reasons for culling, breeds, prion protein-allele distribution); properties of scrapie (genotype-dependent infection rate and incubation periods, and age- and genotype-dependent prevalence of scrapie); properties of the surveillance strategy (selection of sheep for examination, period in which infected sheep are detectable, and properties of the diagnostic tests). For simplification, the prion protein-alleles were grouped into three allele groups: VRQ, ARR, and ARQ' (ARQ' represents ARQ, ARH and AHQ).Through either abattoir surveillance or surveillance of fallen stock, 70% of the detected sheep (compared to 33% in the underlying population). The model output was sensitive to the susceptibility of infection for the genotype ARQ'/ARQ'. The effect was large for abattoir surveillance (increased susceptibility increased the efficiency of abattoir surveillance).     

Evaluation of three LPS-specific monoclonal antibodies for the immunodiagnosis of bovine brucellosis

Bovine sera collected during the Australian brucellosis eradication campaign were used to assess the value of three monoclonal antibodies (MAb Bruce 1, 4 and 7) for the immunodiagnosis of bovine brucellosis in a competitive enzyme immunoassay (CEIA). Each MAb reacted to a different epitope of lipopolysaccharide molecules on the cell surface of Brucella abortus. When the sensitivity of the CEIA was set at 100 per cent so that all infected animals were identified, the specificity of the test using MAb Bruce 1 and Bruce 7 was 69 per cent and 52 per cent, respectively. On the other hand, a quarter of the sera from infected cattle did not inhibit the binding of MAb Bruce 4 to the antigen. With a maximum sensitivity of 75 per cent, the specificity of the CEIA using MAb Bruce 4 was 94 per cent. However, all three MAb cross reacted with sera from sheep infected with Bovis, Histophilus ovis and Actinobacillus seminis.     

Evaluation of three serum i-ELISAs using monoclonal antibodies and protein G as peroxidase conjugate for the diagnosis of bovine brucellosis

Three i-ELISAs using LPS, the immunodominant component of Brucella abortus, were developed with three different conjugates: monoclonal antibodies 1C8 (anti-bovine IgG(1)) and 3H3 (mainly specific for bovine IgG(2) but also reacting with IgG(1)) and protein G (reacts with both bovine IgG subclasses). Using a cut-off value of 2.5U/ml, the i-ELISA with 3H3 as conjugate had a specificity (95% CI: 98.32-99.63%) that was significantly higher than the same assay with 1C8 (95% CI: 96.08-98.26%) or PG (95% CI: 95.83-98.09%). In areas where false positive serological reactions (FPSR) were common, the specificity of the i-ELISAs decreased significantly. The specificity of the i-ELISAs increased with the age of the animals tested, irrespective of the conjugate. The specificity of the i-ELISAs and traditional tests was also examined using sera from animals infected per os with bacteria bearing LPS similar to the Brucella LPS. It appeared that Yersinia enterocolitica O:9, Xanthomonas maltophilia and Salmonella urbana infections induced FPSR both in the i-ELISAs and in the traditional tests, but the 3H3 assay was significantly less prone to produce false positive reactions than the 1C8 and PG assays. The i-ELISAs were more sensitive, allowed earlier detection, and were more persistent than the traditional serological tests both in experimentally and naturally Brucella-infected animals. Weekly i-ELISA monitoring of experimentally infected pregnant heifers (previously vaccinated or not) allowed a prediction of abortion. Furthermore, the 1C8 assay showed significantly higher titres irrespective of day post-infection and vaccination status. The accuracy of the assay could be improved by making use of additional information (e.g. animal age or conjugate) and by selecting appropriate cut-off points on the basis of the prevailing epidemiological situation. The i-ELISAs appear an appropriate choice in order to maintain an official brucellosis-free status because of their sensitivity, early detection and long persistence and, for the same reasons, seem especially valuable for the detection of latent carriers (i.e. animals classified negative by classical serological tests) among imported animals.     

Evaluation of bovine viral diarrhea virus control using a mathematical model of infection dynamics

A mathematical model for infection with bovine viral diarrhea virus (BVDV) was created comprising a series of coupled differential equations. The model architecture is a development of the traditional model framework using susceptible, infectious and removed animals (the SIR model). The model predicts 1.2% persistent infection (within the range of field estimates) and is fairly insensitive to alterations of structure or parameter values. This model allows us to draw important conclusions regarding the control of BVD, particularly with respect to the importance of persistently infected (PI) animals in maintaining BVD as an endemic entity in the herd. Herds without PI animals are likely to experience episodic reproductive losses at intervals of two to three years, unlike herds with PI animals which will not see such marked episodic manifestations of infection. Instead, these herds will experience an initial peak of disease which will settle to low-level chronic reproductive losses. The model indicates that vaccine coverage for herd immunity (to avoid episodic manifestations of disease) need be only 57% without PI animals, although 97% coverage is required when PI animals are present. Analysis of model behavior suggests, a program of detection and removal of PI animals may enhance the effectiveness of a vaccine program provided these animals are in the herd for 10 days or less. The best results would be seen with PI animals in the herd for 5 or fewer days.     

Future options for brucellosis surveillance in New Zealand beef herds

It is probable that bovine brucellosis will be eradicated from New Zealand by 1990. However, continued surveillance for the disease will have to be maintained for a number of years. This paper examines alternative methods of surveillance in beef herds with a view to ensuring that the most cost effective method is used. The three surveillance methods examined are the present automated complement fixation test, abattoir surveillance, and a system based on a delayed hypersensitivity skin test using a purified Brucella protein antigen. It is concluded that despite the relatively low sensitivity of the skin test the probability of its identifying herds as infected is likely to be greater in practice than abattoir surveillance. The skin test is cheaper than the present complement fixation test.     

Future options for brucellosis surveillance in New Zealand beef herds

It is probable that bovine brucellosis will be eradicated from New Zealand by 1990. However, continued surveillance for the disease will have to be maintained for a number of years. This paper examines alternative methods of surveillance in beef herds with a view to ensuring that the most cost effective method is used. The three surveillance methods examined are the present automated complement fixation test, abattoir surveillance, and a system based on a delayed hypersensitivity skin test using a purified Brucella protein antigen. It is concluded that despite the relatively low sensitivity of the skin test the probability of its identifying herds as infected is likely to be greater in practice than abattoir surveil- lance. The skin test is cheaper than the present complement fixation test.     

Effectiveness of various therapeutic regimens for bovine brucellosis

Various chemotherapeutic regimens were evaluated in 48 culture-positive dairy cows. Cessation of shedding of Brucella abortus from udder secretions and absence in selected tissues at necropsy were criteria of success. A combination of a long-acting oxytetracycline and streptomycin eliminated Brucella in 10 of 14 (71.4%) cows. Two cows that were retreated with the same regimen also became culture-negative. Other treatment regimens, including the use of liposome-encapsulated antibiotics, were less successful. Serotests were a poor criterion of effectiveness.     

Real-time PCR carried out on DNA extracted from serum or blood sample is not a good method for surveillance of bovine brucellosis

Bovine brucellosis is endemic in many parts of the world including India. The disease diagnosis and surveillance are usually carried out by serological tests, which however have drawbacks. This study was undertaken to evaluate the potential of real-time PCR (RT-PCR) targeting bcsp31 gene for surveillance of bovine brucellosis. A total of 461 samples, which included 408 stored serum and 53 prospective blood samples, were used. It was found that 33 (7.15 %) samples were positive by RT-PCR, whereas 149 (32.32 %) and 132 (28.63 %) were positive by Rose Bengal plate test (RBPT) or standard agglutination test (STAT), respectively. The results of this study suggest that RT-PCR targeting bcsp31 gene carried out on DNA extracted from serum or blood may not be a suitable method for surveillance of brucellosis in bovines.     

Seroprevalence and risk factors for bovine brucellosis in Jordan

We investigated the seroprevalence and risk factors for Brucella seropositivity in cattle in Jordan. The sera from 671 cows were randomly collected from 62 herds. The antibodies against Brucella were detected using a Rose Bengal plate test and indirect ELISA. A structured questionnaire was used to collect information on the cattle herds'' health and management. A multiple logistic regression model was constructed to identify the risk factors for Brucella seropositivity. The true prevalence of antibodies against Brucella in individual cows and cattle herds was 6.5% and 23%, respectively. The seroprevalence of brucellosis in cows older than 4 years of age was significantly higher than that in the younger cows. The seroprevalence of brucellosis in cows located in the Mafraq, Zarqa and Ma''an governorates was significantly higher than that of the other studied governorates. The multiple logistic regression model revealed that a larger herd size (odd ratio = 1.3; 95% CI: 1.1, 2.6) and mixed farming (OR = 2.0; 95% CI: 1.7, 3.7) were risk factors for cattle seropositivity to Brucella antigens. On the other hand, the use of disinfectants (OR = 1.9; 95% CI: 1.1, 2.1) and the presence of adequate veterinary services (OR = 1.6; 95% CI: 1.2, 3.2) were identified as protective factors.     

Evaluation of trypanosomiasis control alternatives using an epidemiologic simulation model

The effect of various disease-vector control alternatives on the prevalence of trypanosomiasis in southwest Ethiopia was examined with the aid of an epidemiologic model. The alternatives considered included vegetation clearing by manual labor, game elimination, insecticidal spraying from airplanes coupled with settlement, use of sterile male Glossina, avoidance of tsetse infested areas, increasing the resistance of the cattle population, therapy, and combinations of the above methods. First, the currently estimated endemic prevalence of trypanosomiasis (27.3%) in the simulated area of Ethiopia was established and maintained over a 10 year period. Then, various control alternatives were introduced and the simulation was run for an additional 10 years to observe the effect of these control alternatives on the prevalence. The combined use of vegetation clearing, insecticides, therapy, and settlement (or resettlement) was the most effective and feasible method of trypanosomiasis control for the simulated situation.