Latent-class methods to evaluate diagnostics tests for Echinococcus infections in dogs.

BACKGROUND: The diagnosis of canine echinococcosis can be a challenge in surveillance studies because there is no perfect gold standard that can be used routinely. However, unknown test specificities and sensitivities can be overcome using latent-class analysis with appropriate data. METHODOLOGY: We utilised a set of faecal and purge samples used previously to explore the epidemiology of canine echinococcosis on the Tibetan plateau. Previously only the purge results were reported and analysed in a largely deterministic way. In the present study, additional diagnostic tests of copro-PCR and copro-antigen ELISA were undertaken on the faecal samples. This enabled a Bayesian analysis in a latent-class model to examine the diagnostic performance of a genus specific copro-antigen ELISA, species-specific copro-PCR and arecoline purgation. Potential covariates including co-infection with Taenia, age and sex of the dog were also explored. The dependence structure of these diagnostic tests could also be analysed. PRINCIPLE FINDINGS: The most parsimonious result, indicated by deviance-information criteria, suggested that co-infection with Taenia spp. was a significant covariate with the Echinococcus infection. The copro-PCRs had estimated sensitivities of 89% and 84% respectively for the diagnoses of Echinococcus multilocularis and E. granulosus. The specificities for the copro-PCR were estimated at 93 and 83% respectively. Copro-antigen ELISA had sensitivities of 55 and 57% for the diagnosis of E. multilocularis and E. granulosus and specificities of 71 and 69% respectively. Arecoline purgation with an assumed specificity of 100% had estimated sensitivities of 76% and 85% respectively. SIGNIFICANCE: This study also shows that incorporating diagnostic uncertainty, in other words assuming no perfect gold standard, and including potential covariates like sex or Taenia co-infection into the epidemiological analysis may give different results than if the diagnosis of infection status is assumed to be deterministic and this approach should therefore be used whenever possible.

Modelling and spatial discrimination of small mammal assemblages: an example from western Sichuan (China).

We investigate the relationship between landscape heterogeneity and the spatial distribution of small mammals in two areas of Western Sichuan, China. Given a large diversity of species trapped within a large number of habitats, we first classified small mammal assemblages and then modelled the habitat of each in the space of quantitative environmental descriptors. Our original two step "classify then model" procedure is appropriate for the frequently encountered study scenario: trapping data collected in remote areas with sampling guided by expert field knowledge.In the classification step, we defined assemblages by grouping sites of similar species composition and relative densities using an expert-class-merging procedure which reduced redundancy in the habitat factor used within a multinomial logistic regression predicting species trapping probabilities. Assemblages were thus defined as mixtures of small mammal frequency distributions in discrete groups of sampled sites.In the modelling step, assemblages' habitats and environments of the two sampled areas were discriminated in the space of remotely sensed environmental descriptors. First, we compared the discrimination of assemblage/study areas by linear and non-linear forms of Discriminant Analysis (Linear Discriminant Analysis versus Mixture Discriminant Analysis) and of Multiple Regression (Generalized Linear Models versus Multiple Adaptive Regression Splines). The "best" predictive modelling technique was then used to quantify the contribution of each environmental variable in discriminations of assemblages and areas.Mixtures of Gaussians provided a more efficient model of assemblage coverage in environmental space than a single Gaussian cluster model. However, non-linearity in assemblage response to environmental gradients was consistently predicted with lower deviance and misclassification error by Multiple Adaptive Regression Splines. The two study areas were mainly discriminated along vegetation indices. However, although the Normalized Difference Vegetation Index (NDVI) could discriminate forested from non-forested habitats, its power to discriminate assemblages in Maerkang, where a greater diversity of forest habitat was observed, was seen to be limited, and in this case NDVI was outperformed by the Enhanced Vegetation Index (EVI). Our analyses highlight previously unobserved differences between the environments and small mammal communities of two fringe areas of the Tibetan plateau and suggests that a biogeograph-ical approach is required to elucidate ecological processes in small mammal communities and to reduce extrapolation uncertainty in distribution mapping.

Human Echinococcosis: A Neglected Disease?

Human echinococcosis is a zoonotic larval cestode disease usually caused by <I>Echinococcus granulosus</I> or <I>E. multilocularis</I>. Infection is chronic taking years for symptoms to develop. Because diagnosis and treatment are difficult and reservoirs of infection are maintained in domestic livestock, dogs or wildlife, the disease is difficult to assess in terms of public health and requires long-term control interventions. Estimates of numbers of cystic echinococcosis cases that may occur in 2 large endemic zones, North Africa⁄Middle East and China⁄Central Asia, indicates > 423,000 and > 484,000 cases respectively. Globally, 3.6 million DALYs could be lost due to echinoccocosis. Echinococcosis is therefore a neglected disease which is under-reported and requires urgent attention in common with a number of other zoonoses in order to reduce morbidity and to help alleviate poverty in poor pastoral areas of the sub-tropics and temperate zones

Economic effects of echinococcosis in a disease-endemic region of the Tibetan Plateau.

This report attempts to quantify the economic losses due to Echinococcus multilocularis and E. granulosus in Shiqu County, Sichuan, People's Republic of China, as well as illustrate the cost effectiveness of dog anthelmintic prophylaxis combined with a sheep and goat vaccination program in terms of disability-adjusted life years (DALYs) saved. We evaluated human losses associated with treatment costs and loss of income due to morbidity and mortality, in addition to production losses in livestock due to E. granulosus infection. Annual combined human and animal losses (95% confidence interval) is estimated to reach 218,676 U.S. dollars (189,850-247,871 U.S. dollars) if only liver-related losses in sheep, goats, and yaks are taken into account. This equates to approximately 3.47 U.S. dollars per person annually or 1.4% of per capita gross domestic product. However, total annual losses can be nearly 1,000,000 U.S. dollars if additional livestock production losses are assumed. Eventual prevention of 65-95% of annual losses due to cystic echinococcosis is suggested with proposed biannual dog anthelmintic prophylaxis and a sheep and goat vaccination program. Prevention of 9-50% of human alveolar echinococcosis-associated losses is suggested based on stochastic models for the current epidemiologic situation. The median estimated cost of the program would be approximately 56,000 U.S. dollars per year, which is a fraction of the estimated combined livestock and human financial losses due to the disease. Overall cost for the proposed control program is within the World Health Organization second most cost-effective band of less than 150 U.S. dollars per DALY averted. However, cost per DALY averted would be less than 25 U.S. dollars dollars for the human health sector if cost sharing was implemented between the public health and agricultural sectors based on proportional benefit from control.

Modeling the transmission of Echinococcus granulosus and Echinococcus multilocularis in dogs for a high endemic region of the Tibetan plateau.

Echinococcus granulosus and Echinococcus multilocularis abundance and prevalence data, for domestic dogs of Shiqu County, Sichuan Province, People's Republic of China, were fitted to mathematical models to evaluate transmission parameters. Abundance models, assuming the presence and absence of immunity, were fit for both E. granulosus and E. multilocularis using Bayesian priors, maximum likelihood, and Monte Carlo sampling techniques. When the models were compared, using the likelihood ratio test for nested models, the model assuming the presence of immunity was the best fit for E. granulosus infection, with a purgation based prevalence of 8% (true prevalence interval of 8-19% based on the sensitivity of purgation) and a mean abundance of 80 parasites per dog, with an average infection pressure of 560 parasites per year. In contrast, the model assuming the absence of immunity was the best fit for E. multilocularis infection, with a purgation based prevalence of 12% (true prevalence interval of 13-33% based on the sensitivity of purgation) and a mean abundance of 131 parasites per dog, with an average infection pressure of 334 or 533 parasites per year assuming a 5 or 3 month parasite life expectancy, respectively. The prevalence data for both parasites was then fit to a set of differential equations modeling the transition between infection states in order to determine number of infectious insults per year. Infection pressure was 0.21, with a 95% credibility interval of 0.12 to 0.41, infections per year for E. granulosus and 0.52, with a 95% credibility interval of 0.29-0.77, infections per year for E. multilocularis assuming a 5 month parasite lifespan or 0.85, with a 95% credibility interval of 0.47-1.25 infections per year, assuming a 3 month E. multilocularis lifespan in dogs.

Echinococcosis in Tibetan populations, western Sichuan Province, China.

We screened 3,199 people from Shiqu County, Sichuan Province, China, for abdominal echinococcosis (hydatid disease) by portable ultrasound combined with specific serodiagnostic tests. Both cystic echinococcosis (CE) (Echinococcus granulosus infection) and alveolar echinococcosis (AE) (E. multilocularis) were co-endemic in this area at the highest village prevalence values recorded anywhere in the world: 12.9% were infected with one or the other form (6.8% CE and 6.2% AE). Prevalences of both CE and AE were significantly higher in female than male patients and increased with the age of the person screened. Pastoral herdsmen were at highest risk for infection (prevalence 19.0%). Prevalence of CE varied in 5 townships from 0% to 12.1%, whereas AE prevalence ranged from 0% to 14.3%. Risk factors associated with both infections included the number of owned dogs, frequency of contact with dogs, and sources of drinking water.

Use of disability adjusted life years in the estimation of the disease burden of echinococcosis for a high endemic region of the Tibetan plateau.

Shiqu County, located on the Tibetan plateau of western China, has an extremely high prevalence of both human alveolar echinococcosis (AE), and cystic echinococcosis (CE). The short form 12 version 2 quality of life survey, which was used to evaluate the extent to which morbidity associated with echinococcosis should be accounted, verified that there was a significant reduction in the mean health scores in all categories for individuals diagnosed with abdominal echinococcosis compared with an age and sex cross-matched population. Results of a larger ultrasound survey, which screened 3135 subjects, demonstrated that the prevalence rates of AE and CE were both approximately 6% with a combined prevalence rate of 11.4%. Prevalence rates adjusted for the age and sex structure of Shiqu County were 4.6% for AE and 4.9% for CE with an estimated overall adjusted prevalence rate of 9.5%. The burden of disease associated with echinococcosis was calculated using disability adjusted life years (DALYs) based on these estimated prevalence rates. Monte-Carlo techniques were used to model the uncertainty in the prevalence estimates and the disability weights. Using these methods, we estimated that the total numbers of DALYs lost due echinococcosis was 50,933 (95% confidence interval [CI] = 41,995-61,026). The DALYs lost consisted of approximately 32,978 (95% CI = 25,019-42,422) due to AE and 17,955 (95% CI = 14,268-22,128) due to CE and suggests an average of approximately 0.81 DALY lost per person. This study has clearly shown that the impact of DALYs lost due to echinococcosis, in terms of medical treatment costs, lost income, and physical and social suffering, is likely to be substantial in this highly endemic region of China.

Control of echinococcosis and cysticercosis: a public health challenge to international cooperation in China.

Echinococcosis, both cystic and alveolar, and Taenia solium cysticercosis are the most serious zoonotic cestodoses worldwide. Because of the emerging importance of these diseases in China, several international workshops and meetings were held in this country from 1998 to 2001. Based on round table discussions in Chengdu 2000, the proposal of a strategy to control echinococcosis and cysticercosis has been prepared in China. It includes a comprehensive approach based on a careful analysis of the local situations (particularly concerning the particularities of the cycle, ecology, and ethology of the animal hosts, and behavioral characteristics of the population at risk), the use of newly developed tools both in animals and human (immunology, molecular biology, and imaging), and the association of the traditional control measures (control of slaughtering, antiparasitic treatment and control of the definitive hosts, and health education) with more recent developments such as vaccination of the intermediate hosts. Plans on for the control of echinococcosis and cysticercosis in China are summarized.

β-AR density relativity of porcine myocardial tissue and circulating lymphocytes and its significance / 中华急诊医学杂志

Objective　To study β-AR density relativity between porcine myocardial tissue and circulating lymphocytes and clinical significance ．Methods　 48 porcines(seven months old），were　taken a few of myocardial tissue and peripheral blood．Assay　β-AR density with radioactive isotope to study the　relativity．Results　Scatter plot of β-AR　density　 circulating lymphocytes and myocardial tissue showed　 linear　Correlation（r＝0.845，P＜0.001　Y＝0.002527X＋0.726）．Conclusion　There　was　obvious　 correlation on β-AR　density in circulating lymphocytes and myocardial membrane　of pigs．Determination of β-AR　density　in　circulating lymphocytes can reflect alteration of that in myocardial tissue．Therefore，we can use it to monitor and investigate　self-induced and drug-induced β-AR changes．