Computer simulation to support policy-making in Aujeszky's disease control

Aujeszky's disease is a contagious viral disease that affects the central nervous system of pigs. Several eradication programs or measures are available, each of them providing different results. Determining the preferred strategy is to a large extent a matter of economic consideration.Under the EU rules, countries or regions that are Aujeszky-free can ban imports of breeding animals carrying antibodies of the disease; movements to Aujeszky-free areas from other areas of both breeding and rearing pigs are subject to strict conditions and controls, which differ depending on whether or not the area of origin has an EU-approved eradication program. If important import destinations achieve disease-free status, exporting countries that have failed to eradicate the disease will be severely penalized. Therefore, sterner demands are to be expected considering control and eradication of Aujeszky's disease in the Netherlands in the future. To meet these demands, the objective of this study was to develop a computer simulation environment in which "what-if' scenarios can be performed to explore the epidemiological and economic effects of different Aujeszky's disease control programs. The model can be used to support the choice of the optimal eradication program under various conditions, in particular from an epidemiological and economic point of view.First, a flexible economic framework to evaluate Aujeszky's disease eradication programs was developed, and illustrated with an example (Chapter 2). The framework has four elements: changes in percentage of infectious herds, changes in product quantities, changes in product prices and economic integration. Each of these elements is defined as a separate module in the simulation model and has its own input and output data, depending on the control strategy under consideration. With these elements all epidemiological and economic aspects of the disease can be monitored over time.In an illustrative example, probability distributions of the number of infectious herds corresponding to each control strategy were compared and the optimal strategy was chosen, according to the risk attitude of the decision maker. The framework can be considered a standardized approach in comparing and selecting animal health control strategies by integrating technical and economic data and principles.To obtain epidemiological information with respect to the control of Aujeszky's disease virus, an epidemiological state-transition simulation model was constructed to evaluate the spread of the virus (Chapter 3). In the model, the population of herds in the Netherlands is subdivided into four herd types: great-grandparent stock+multiplier, rearing, farrowing and fattening. Every time step, each herd is in one of 32 states per herd type. The states are based on (1) the reproduction ratio R ind , which is the number of individuals infected by one infectious individual, (2) the prevalence for each value of R ind and (3) the expected number of infectious animals in an infectious herd within each prevalence range of the herds. The different values Of R ind are based as much as possible on field data and experiments, where different vaccination strategies were applied.The transition matrix with the probabilities of every possible transition from one state to another was calculated on a weekly base. With this matrix the distribution of herds over states from week to week was derived. To include the non-linearity of the transmission process, the transmission probabilities from non-infectious to either non-infectious or infectious were developed such that they depend on the state vector itself The fraction of herds that becomes infectious equals one minus the fraction of herds that has not been infected by the virus emitted by infectious herds.Calculations revealed that infection in the Dutch pig population would not disappear without vaccination, nor with a vaccination scheme in which sows were vaccinated less than 3 times per year and fattening pigs once per cycle (Chapter 4). The infection, however, would be eradicated within 2 to 3 years, if sows were vaccinated 3 or 4 times per year and fattening pigs twice per cycle. The outcome turned out to be sensitive to the impact of other than animal contacts on the number of new effective virus introductions per time unit.The structure of the production pyramid and herd density in the affected regions were other important factors which influenced the course of infection. To examine the impact of these factors the total number of herds in the Netherlands were further subdivided into four regions (North, East, West-Middle, South).Outcomes showed that the percentage of infectious herds in equilibrium was highest for rearing herds (76.3%) and lowest for great-grandparent stock+multiplier herds (20.0%) if no vaccination was done. The herd type "fattening" had more impact on the effectivity of the different vaccination strategies than the herd type "farrowing". This difference is becoming less if more intensive vaccination strategies are applied. Besides the difference in herd type, also herd density and the percentage of non-vaccinated herds were an important factor in the eradication process.After simulating these epidemiological characteristics of Aujeszky's disease virus, market outcomes and pig producers' returns were simulated under different scenarios with respect to closure of export markets for live piglets and fattened pigs (Chapter 5). If the Netherlands fails to eradicate Aujeszky's disease before its trading partners in these markets, live piglet exports would be banned, reducing industry revenue and export earnings by about 9% and 10% respectively in the medium term. If exports of live fattened pigs are also banned, the reductions are 26 and 32% respectively. The piglet-producing sector would be moreseverely affected than the fattening sector. The model also showed that, if export markets for carcasses were also to close for an unspecified food safety reason, capacity of the industry would fall over 50%.Lastly four control strategies to eradicate Aujeszky's disease virus in the Netherlands were compared epidemiologically and economically (Chapter 6). Vaccination decreased the number of cases per production loss. The decrease was largest if vaccination strategy changed from "no vaccination" to the less intensive vaccination. Extra vaccinations under more intensive vaccination strategies, however, still had impact. The attendant costs were highest per dead animal (especially for gilts) and per abortion. Growth delay of gilts and piglets turned out to be of minor importance.The sales distribution on the piglet markets (import, export and on the domestic markets) was particularly influenced by vaccination, but the decreases in revenues were only less than 4.3%. The only exception was the number of piglets and live animals that were imported into the Netherlands, which decreased by more than 15% and about 9% respectively. The accompanying revenues from piglets and fattened pigs were highest if "no vaccination" was done. Compared with the revenue in this strategy, this difference is greatest on the piglet market, as the decrease in revenue was about 3.6%, while the decrease was about 0.55% on the market of fattened pigs.According to the resulting present values over a period of 10 years, "no vaccination" is economically the best solution only if no trade restrictions are to be expected. Economically speaking, however, the most intensive vaccination strategy should be applied, if an export ban of two years on live animals to, for instance, Germany is expected within 10 years after the start of the vaccination strategy. A prolonged export ban makes this strategy even more favourable. From an economic point of view intermediate vaccination strategies are never preferred.The main conclusions of this thesis are:- State-transition simulation proves to be an appropriate method to evaluate transmission of Aujeszky's disease virus. The epidemiological information obtained can well be used in economic evaluation of different control strategies.- Aujeszky's disease is only eradicated in the Netherlands if the most intensive vaccination strategy (≥3 times per year) is applied for breeding sows, and fattening pigs are vaccinated at least once per cycle.- If applying the most intensive vaccination strategy, it takes about 200 weeks for an average herd to become non-infectious.- The relative impact of other than animal contacts on the number of new virus introductions increases from 4% to 98%, if the vaccination strategy is changed from "no vaccination" to the most intensive vaccination program.- Subdivision of the total population into herd types and regions is important to enhance insight into transmission of infection in the pig population and to support decision making at regional level.- Price equilibrium models can well estimate the short-term changes in prices as well as those in the medium term. To accomplish this, it is of importance that sufficient historical data about quantities, prices and the infections occurred are available to estimate the required parameters accurately. A monthly data-set of about 10 years turned out to be sufficient.- Direct production losses from Aujeszky's disease virus are less than 6% of the vaccination costs when vaccination is carried out. More than 80% of these losses are caused by growth delay of fattening pigs.- The most intensive vaccination strategy (i.e., sows are vaccinated 3 or 4 times per year and fattening and rearing pigs twice per cycle) is economically preferred if an export ban on part of the live animals is expected during at least 2 years within 10 years after the start of the vaccination program. If this is not to be expected then "no vaccination" turns out to be the best strategy. The risk of an export ban on live animals should justify the eradication of the virus from the population.- For the current situation in the Netherlands it is economically preferred to start blood sampling all sows and remove the gE-positive animals instead of continuing vaccination, provided that the additional risk of new introductions of the virus is sufficiently limited

Clinical Relevance of Non-Tuberculous Mycobacteria in Zambia

Tuberculosis, especially due to the high prevalence of HIV, remains a problem of large dimension in Africa and Mycobacterium tuberculosis is the most important causative agent. However, it is known that in developed countries also nontuberculous mycobacteria (NTM) play a significant role in the aetiology of tuberculosis-like syndromes, especially in HIV-positive patients. In Africa, the contribution of NTM to the problem of tuberculosis has hardly been examined. Southern Africa is the most affected sub-region in Africa concerning HIV/AIDS, where HIV prevalence rates have stabilized at high levels, exceeding 25% in some countries, while in other African countries, the epidemic is still growing. In Zambia the estimated adult (15-49 yrs) prevalence of HIV/AIDS amounted 13.5-20% in 2003 (61). NTM disease was one of the major AIDS-defining diseases in industrialized countries before the era of highly active antiretroviral therapy (HAART). Such infections have been thought to be less frequent in sub-Saharan Africa, but with the remaining doubt that the unavailability of the laboratory facilities and sophisticated radiological tools required to diagnose such disease may lead to underestimating of their true frequency (9,12,24,27,37,41,47). Whereas an international prospective study showed that NTM prevalence for disease was five to 10-fold lower in Kenya than in the United States of America or Northern Europe (24), a few hospital-based studies have reported a different prevalence for disease than reported in Kenya (9,12,27,37,41,47). For an overview of the literature on prevalence/incidence rates of colonization/infection/disease of NTM in Africa see Table 1 in the introduction of this thesis. Because the clinical relevance of the isolation of NTM in HIV-positive as well as in HIV-negative patients in Africa may be underestimated in this study, the meaning of NTM was examined in more detail in Zambia

Multipele dermoïd sinuscysten op de kop van een dwergschnauzer

A one-year-and-nine-months-old, neutered, female Miniature schnauzer was presented to the primary care veterinarian with a skin lesion between the eyebrows. There were multiple papulae present at birth, and later, small fistulae with protruding hair bundles appeared. Topical antibiotic therapy and epilation of the hairs only brought temporary relief and a presumptive diagnosis of dermoid sinus cysts was made. The dog was referred and the skin lesions were surgically excised. During histopathological examination, the lesion was diagnosed as multiple dermoid sinus cysts, a consequence of the incomplete separation of the ectoderm during embryogenesis. Depending on the depth of the tubular dermal invaginations and the location of the lesions, different types have been recognized. This is the third dog described in the literature with dennoid sinus cysts on the head

Clinical Relevance of Nontuberculous Mycobacteria, Oman

Little is known about the clinical relevance of nontuberculous mycobacteria (NTM) in the Arabian Peninsula. We assessed the prevalence and studied a random sample of isolates at a reference laboratory in Muscat, Oman. NTM cause disease in this region, and their prevalence has increased

Mycobacterium lentiflavum in Drinking Water Supplies, Australia

Humans may acquire infection from potable water

Rapid and Accurate Detection of Mycobacterium tuberculosis in Sputum Samples by Cepheid Xpert MTB/RIF Assay-A Clinical Validation Study

Background: A crucial impediment to global tuberculosis control is the lack of an accurate, rapid diagnostic test for detection of patients with active TB. A new, rapid diagnostic method, (Cepheid) Xpert MTB/RIF Assay, is an automated sample preparation and real-time PCR instrument, which was shown to have good potential as an alternative to current reference standard sputum microscopy and culture.Methods: We performed a clinical validation study on diagnostic accuracy of the Xpert MTB/RIF Assay in a TB and HIV endemic setting. Sputum samples from 292 consecutively enrolled adults from Mbeya, Tanzania, with suspected TB were subject to analysis by the Xpert MTB/RIF Assay. The diagnostic performance of Xpert MTB/RIF Assay was compared to standard sputum smear microscopy and culture. Confirmed Mycobacterium tuberculosis in a positive culture was used as a reference standard for TB diagnosis.Results: Xpert MTB/RIF Assay achieved 88.4% (95% CI = 78.4% to 94.9%) sensitivity among patients with a positive culture and 99% (95% CI = 94.7% to 100.0%) specificity in patients who had no TB. HIV status did not affect test performance in 172 HIV-infected patients (58.9% of all participants). Seven additional cases (9.1% of 77) were detected by Xpert MTB/RIF Assay among the group of patients with clinical TB who were culture negative. Within 45 sputum samples which grew non-tuberculous mycobacteria the assay's specificity was 97.8% (95% CI = 88.2% to 99.9%).Conclusions: The Xpert MTB/RIF Assay is a highly sensitive, specific and rapid method for diagnosing TB which has potential to complement the current reference standard of TB diagnostics and increase its overall sensitivity. Its usefulness in detecting sputum smear and culture negative patients needs further study. Further evaluation in high burden TB and HIV areas under programmatic health care settings to ascertain applicability, cost-effectiveness, robustness and local acceptance are required

Nontuberculous mycobacteria, Zambia

Clinical relevance of nontuberculous mycobacteria (NTM) isolated from 180 chronically ill patients and 385 healthy controls in Zambia was evaluated to examine the contribution of these isolates to tuberculosis (TB)-like disease. The proportion of NTM-positive sputum samples was significantly higher in the patient group than in controls; 11% and 6%, respectively (p<0.05). NTM-associated lung disease was diagnosed for 1 patient, and a probable diagnosis was made for 3 patients. NTM-positive patients and controls were more likely to report vomiting and diarrhea and were more frequently underweight than the NTM-negative patients and controls. Chest radiographs of NTM-positive patients showed deviations consistent with TB more frequently than those of controls. The most frequently isolated NTM was Mycobacterium avium complex. Multiple, not previously identified mycobacteria (55 of 171 NTM) were isolated from both groups. NTM probably play an important role in the etiology of TB-like diseases in Zambia

CCL2/MCP-I Genotype-Phenotype Relationship in Latent Tuberculosis Infection

Among the known biomarkers, chemokines, secreted by activated macrophages and T cells, attract groups of immune cells to the site of infection and may determine the clinical outcome. Association studies of CCL-2/MCP-1 -2518 A/G functional SNP linked to high and low phenotypes with tuberculosis disease susceptibility have shown conflicting results in tuberculosis. Some of these differences could be due the variability of latent infection and recent exposure in the control groups. We have therefore carried out a detailed analysis of CCL-2 genotype SNP -2518 (A/G transition) with plasma CCL-2 levels and related these levels to tuberculin skin test positivity in asymptomatic community controls with no known exposure to tuberculosis and in recently exposed household contacts of pulmonary tuberculosis patients. TST positivity was linked to higher concentrations of plasma CCL2 (Mann Whitney U test; p = 0.004) and was more marked when the G allele was present in TST+ asymptomatic controls (A/G; p = 0.01). Recent exposure also had a significant effect on CCL-2 levels and was linked to the G allele (p = 0.007). Therefore association studies for susceptibility or protection from disease should take into consideration the PPD status as well as recent exposure of the controls group used for comparison. Our results also suggest a role for CCL-2 in maintaining the integrity of granuloma in asymptomatic individuals with latent infection in high TB burden settings. Therefore additional studies into the role of CCL-2 in disease reactivation and progression are warranted