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1.  Dynamics of the Force of Infection: Insights from Echinococcus multilocularis Infection in Foxes 
Characterizing the force of infection (FOI) is an essential part of planning cost effective control strategies for zoonotic diseases. Echinococcus multilocularis is the causative agent of alveolar echinococcosis in humans, a serious disease with a high fatality rate and an increasing global spread. Red foxes are high prevalence hosts of E. multilocularis. Through a mathematical modelling approach, using field data collected from in and around the city of Zurich, Switzerland, we find compelling evidence that the FOI is periodic with highly variable amplitude, and, while this amplitude is similar across habitat types, the mean FOI differs markedly between urban and periurban habitats suggesting a considerable risk differential. The FOI, during an annual cycle, ranges from (0.1,0.8) insults (95% CI) in urban habitat in the summer to (9.4, 9.7) (95% CI) in periurban (rural) habitat in winter. Such large temporal and spatial variations in FOI suggest that control strategies are optimal when tailored to local FOI dynamics.
Author Summary
Human alveolar echinococcosis (AE) is caused by the fox tapeworm E. multilocularis and has a high fatality rate if untreated. The frequency of the tapeworm in foxes can be reduced through the regular distribution of anthelmintic baits and thus decrease the risk of zoonotic transmission. Here, we estimate the force of infection to foxes using a mathematical model and data from necropsied foxes. The results suggest that the frequency of anthelmintic baiting of foxes can be optimised to local variations in transmission that depend upon season and type of fox habitat.
doi:10.1371/journal.pntd.0002731
PMCID: PMC3961194  PMID: 24651596
2.  The Burden of Parasitic Zoonoses in Nepal: A Systematic Review 
Background
Parasitic zoonoses (PZs) pose a significant but often neglected threat to public health, especially in developing countries. In order to obtain a better understanding of their health impact, summary measures of population health may be calculated, such as the Disability-Adjusted Life Year (DALY). However, the data required to calculate such measures are often not readily available for these diseases, which may lead to a vicious circle of under-recognition and under-funding.
Methodology
We examined the burden of PZs in Nepal through a systematic review of online and offline data sources. PZs were classified qualitatively according to endemicity, and where possible a quantitative burden assessment was conducted in terms of the annual number of incident cases, deaths and DALYs.
Principal Findings
Between 2000 and 2012, the highest annual burden was imposed by neurocysticercosis and congenital toxoplasmosis (14,268 DALYs [95% Credibility Interval (CrI): 5450–27,694] and 9255 DALYs [95% CrI: 6135–13,292], respectively), followed by cystic echinococcosis (251 DALYs [95% CrI: 105–458]). Nepal is probably endemic for trichinellosis, toxocarosis, diphyllobothriosis, foodborne trematodosis, taeniosis, and zoonotic intestinal helminthic and protozoal infections, but insufficient data were available to quantify their health impact. Sporadic cases of alveolar echinococcosis, angiostrongylosis, capillariosis, dirofilariosis, gnathostomosis, sparganosis and cutaneous leishmaniosis may occur.
Conclusions/Significance
In settings with limited surveillance capacity, it is possible to quantify the health impact of PZs and other neglected diseases, thereby interrupting the vicious circle of neglect. In Nepal, we found that several PZs are endemic and are imposing a significant burden to public health, higher than that of malaria, and comparable to that of HIV/AIDS. However, several critical data gaps remain. Enhanced surveillance for the endemic PZs identified in this study would enable additional burden estimates, and a more complete picture of the impact of these diseases.
Author Summary
Various parasites that infect humans require animals in some stage of their life cycle. Infection with these so-called zoonotic parasites may vary from asymptomatic carriership to long-term morbidity and even death. Although data are still scarce, it is clear that parasitic zoonoses (PZs) present a significant burden for public health, particularly in poor and marginalized communities. So far, however, there has been relatively little attention to this group of diseases, causing various PZs to be labeled neglected tropical diseases. In this study, the authors reviewed a large variety of data sources to study the relevance and importance of PZs in Nepal. It was found that a large number of PZs are present in Nepal and are imposing an impact higher than that of malaria and comparable to that of HIV/AIDS. These results therefore suggest that PZs deserve greater attention and more intensive surveillance. Furthermore, this study has shown that even in settings with limited surveillance capacity, it is possible to quantify the impact of neglected diseases and, consequently, to break the vicious circle of neglect.
doi:10.1371/journal.pntd.0002634
PMCID: PMC3879239  PMID: 24392178
3.  Molecular Characterization of Echinococcus granulosus Cysts in North Indian Patients: Identification of G1, G3, G5 and G6 Genotypes 
Background
Cystic echinococcosis (CE) caused by the Echinococcus granulosus, is a major public health problem worldwide, including India. The different genotypes of E. granulosus responsible for human hydatidosis have been reported from endemic areas throughout the world. However, the genetic characterization of E. granulosus infecting the human population in India is lacking. The aim of study was to ascertain the genotype(s) of the parasite responsible for human hydatidosis in North India.
Methodology/Principal Findings
To study the transmission patterns of E. granulosus, genotypic analysis was performed on hydatid cysts obtained from 32 cystic echinococcosis (CE) patients residing in 7 different states of North India. Mitochondrial cytochrome c oxidase subunit1 (cox1) sequencing was done for molecular identification of the isolates. Most of the CE patients (30/32) were found to be infected with hydatid cyst of either G3 (53.1%) or G1 (40.62%) genotype and one each of G5 (cattle strain) and G6 (camel strain) genotype.
Conclusions/Significance
These findings demonstrate the zoonotic potential of G1 (sheep strain) and G3 (buffalo strain) genotypes of E. granulosus as these emerged as predominant genotypes infecting the humans in India. In addition to this, the present study reports the first human CE case infected with G5 genotype (cattle strain) in an Asian country and presence of G6 genotype (camel strain) in India. The results may have important implications in the planning of control strategies for human hydatidosis.
Author Summary
Cystic echinococcosis caused by Echinococcus granulosus is a widespread zoonotic disease. This cestode parasite is a complex of genetic variants and to date, ten distinct genotypes (genotypes G1–G10) have been identified on the basis of mitochondrial DNA sequences. The strain variation in E. granulosus may influence life-cycle patterns, host range, antigenicity and transmission dynamics. The disease is endemic in different parts of India. Although the presence of G1, G2, G3 and G5 has been reported in animal isolates in India, the zoonotic potential of the different genotypes has not been evaluated. In the present study, a genotype analysis was carried out in hydatid cysts collected from 32 cystic echinococcosis patients residing in North India. Most of the CE patients (30/32) were found to be infected with hydatid cyst of either G3 (53.1%) or G1 (40.62%) genotype and one each of G5 (cattle strain) and G6 (camel strain) genotype.
doi:10.1371/journal.pntd.0002262
PMCID: PMC3681628  PMID: 23785531
4.  A Systematic Review of the Epidemiology of Echinococcosis in Domestic and Wild Animals 
Background
Human echinococcosis is a neglected zoonosis caused by parasites of the genus Echinococcus. The most frequent clinical forms of echinococcosis, cystic echinococcosis (CE) and alveolar echinococcosis (AE), are responsible for a substantial health and economic burden, particularly to low-income societies. Quantitative epidemiology can provide important information to improve the understanding of parasite transmission and hence is an important part of efforts to control this disease. The purpose of this review is to give an insight on factors associated with echinococcosis in animal hosts by summarising significant results reported from epidemiological studies identified through a systematic search.
Methodology and Principal Findings
The systematic search was conducted mainly in electronic databases but a few additional records were obtained from other sources. Retrieved entries were examined in order to identify available peer-reviewed epidemiological studies that found significant risk factors for infection using associative statistical methods. One hundred studies met the eligibility criteria and were suitable for data extraction. Epidemiological factors associated with increased risk of E. granulosus infection in dogs included feeding with raw viscera, possibility of scavenging dead animals, lack of anthelmintic treatment and owners' poor health education and indicators of poverty. Key factors associated with E. granulosus infection in intermediate hosts were related to the hosts' age and the intensity of environmental contamination with parasite eggs. E. multilocularis transmission dynamics in animal hosts depended on the interaction of several ecological factors, such as hosts' population densities, host-prey interactions, landscape characteristics, climate conditions and human-related activities.
Conclusions/Significance
Results derived from epidemiological studies provide a better understanding of the behavioural, biological and ecological factors involved in the transmission of this parasite and hence can aid in the design of more effective control strategies.
Author Summary
Echinococcosis is considered a neglected zoonotic disease caused by the larval form of Echinococcus spp. tapeworms. Humans become infected through the accidental intake of parasitic eggs excreted by the faeces of definitive hosts (dogs, foxes and other canids). Infection involves the development of cysts, primarily in the lungs and liver, causing damage as they enlarge like a slowly growing tumor. Transmission is facilitated by the general lack of awareness of infection factors and epidemiological models can identify them. Nevertheless, there has never been a systematic review summarizing the significant determinants for echinococcosis in animals. One hundred publications were included in the results after evaluating 1,935 entries and screening the references lists of the eligible papers. Principal factors associated with canine infection included the access of dogs to infected offal, allowing dogs to roam free, being a young and/or male dog and social behaviours linked with poor health conditions and poor living environments of dog owners. Ecological factors influencing E. multilocularis transmission encompassed population densities of foxes and rodents, predator-prey relationships, geographical characteristics, climate conditions and the movement of foxes towards urban areas. These findings are important, as intervention to control echinococcosis requires intervention in animal populations.
doi:10.1371/journal.pntd.0002249
PMCID: PMC3674998  PMID: 23755310
5.  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.
Author Summary
Dogs are a key definitive host of Echinococcus spp; hence, accurate diagnosis in dogs is important for the surveillance and control of echinococcosis. A perfect diagnostic test would detect every infected dog (100% sensitivity) whilst never giving a false positive reaction in non-infected dogs (100% specificity). Since no such test exists, it is important to understand the performance of available diagnostic techniques. We used the results of a study that used three diagnostic tests on dogs from the Tibetan plateau, where there is co-endemicity of E. granulosus and E. multilocularis. In this study opro-antigen ELISA and copro-PCR diagnostic tests were undertaken on faecal samples from all animals. The dogs were also purged with arecoline hydrobromide to recover adult parasites as a highly specific but relatively insensitive third diagnostic test. We used a statistical approach (Bayesian latent-class models) to estimate simultaneously the sensitivities of all three tests and the specificities of the copro-antigen and copro-PCR tests. We also analysed how some determinants of infection can affect parasite prevalence. This approach provides a robust framework to increase the accuracy of surveillance and epidemiological studies of echinococcosis by overcoming the problems of poor diagnostic test performance.
doi:10.1371/journal.pntd.0002068
PMCID: PMC3573084  PMID: 23459420
6.  Toxoplasma gondii Infection in Kyrgyzstan: Seroprevalence, Risk Factor Analysis, and Estimate of Congenital and AIDS-Related Toxoplasmosis 
Background
HIV-prevalence, as well as incidence of zoonotic parasitic diseases like cystic echinococcosis, has increased in the Kyrgyz Republic due to fundamental socio-economic changes after the breakdown of the Soviet Union. The possible impact on morbidity and mortality caused by Toxoplasma gondii infection in congenital toxoplasmosis or as an opportunistic infection in the emerging AIDS pandemic has not been reported from Kyrgyzstan.
Methodology/Principal Findings
We screened 1,061 rural and 899 urban people to determine the seroprevalence of T. gondii infection in 2 representative but epidemiologically distinct populations in Kyrgyzstan. The rural population was from a typical agricultural district where sheep husbandry is a major occupation. The urban population was selected in collaboration with several diagnostic laboratories in Bishkek, the largest city in Kyrgyzstan. We designed a questionnaire that was used on all rural subjects so a risk-factor analysis could be undertaken. The samples from the urban population were anonymous and only data with regard to age and gender was available. Estimates of putative cases of congenital and AIDS-related toxoplasmosis in the whole country were made from the results of the serology. Specific antibodies (IgG) against Triton X-100 extracted antigens of T. gondii tachyzoites from in vitro cultures were determined by ELISA. Overall seroprevalence of infection with T. gondii in people living in rural vs. urban areas was 6.2% (95%CI: 4.8–7.8) (adjusted seroprevalence based on census figures 5.1%, 95% CI 3.9–6.5), and 19.0% (95%CI: 16.5–21.7) (adjusted 16.4%, 95% CI 14.1–19.3), respectively, without significant gender-specific differences. The seroprevalence increased with age. Independently low social status increased the risk of Toxoplasma seropositivity while increasing numbers of sheep owned decreased the risk of seropositivity. Water supply, consumption of unpasteurized milk products or undercooked meat, as well as cat ownership, had no significant influence on the risk for seropositivity.
Conclusions
We present a first seroprevalence analysis for human T. gondii infection in the Kyrgyz Republic. Based on these data we estimate that 173 (95% CI 136–216) Kyrgyz children will be born annually to mothers who seroconverted to toxoplasmosis during pregnancy. In addition, between 350 and 1,000 HIV-infected persons are currently estimated to be seropositive for toxoplasmosis. Taken together, this suggests a substantial impact of congenital and AIDS-related symptomatic toxoplasmosis on morbidity and mortality in Kyrgyzstan.
Author Summary
A serological study on toxoplasmosis was undertaken in a rural and urban population in Kyrgyzstan. The observed seroprevalence was adjusted because of differences between age and gender stratifications in the study group compared to population census figures. This gave an estimated seroprevalence in rural and urban populations of 5.1% and 16.4% respectively. In our analysis we determined the risk-factors for infection in the rural population to be age, low social-status and low number of sheep owned. While the seroprevalence in this rural population was relatively low, the seroprevalence found in the urban population of Bishkek correlated better with international data. Extrapolating from our data, about 173 seroconversions during pregnancy may be expected annually in Kyrgyzstan. In addition, considering a prevalence of HIV-Toxoplasma-co-infection between 7/100,000 (official HIV-prevalence data) and 19.4/100,000 (UNAIDS-estimates), 350–1,000 people are at risk for AIDS-related toxoplasmosis. Therefore, in the face of the rising prevalence of HIV infection education of medical personnel on treatment and prevention of toxoplasmosis is recommended.
doi:10.1371/journal.pntd.0002043
PMCID: PMC3566989  PMID: 23409201
7.  A tutorial in estimating the prevalence of disease in humans and animals in the absence of a gold standard diagnostic 
Epidemiological methods for estimating disease prevalence in humans and other animals in the absence of a gold standard diagnostic test are well established. Despite this, reporting apparent prevalence is still standard practice in public health studies and disease control programmes, even though apparent prevalence may differ greatly from the true prevalence of disease. Methods for estimating true prevalence are summarized and reviewed. A computing appendix is also provided which contains a brief guide in how to easily implement some of the methods presented using freely available software.
doi:10.1186/1742-7622-9-9
PMCID: PMC3558341  PMID: 23270542
8.  The Monetary Burden of Cystic Echinococcosis in Iran 
Cystic echinococcosis (CE) is a globally distributed parasitic infection of humans and livestock. The disease is of significant medical and economic importance in many developing countries, including Iran. However, the socioeconomic impact of the disease, in most endemic countries, is not fully understood. The purpose of the present study was to determine the monetary burden of CE in Iran. Epidemiological data, including prevalence and incidence of CE in humans and animals, were obtained from regional hospitals, the scientific literature, and official government reports. Economic data relating to human and animal disease, including cost of treatment, productivity losses, and livestock production losses were obtained from official national and international datasets. Monte Carlo simulation methods were used to represent uncertainty in input parameters. Mean number of surgical CE cases per year for 2000–2009 was estimated at 1,295. The number of asymptomatic individuals living in the country was estimated at 635,232 (95% Credible Interval, CI 149,466–1,120,998). The overall annual cost of CE in Iran was estimated at US$232.3 million (95% CI US$103.1–397.8 million), including both direct and indirect costs. The cost associated with human CE was estimated at US$93.39 million (95% CI US$6.1–222.7 million) and the annual cost associated with CE in livestock was estimated at US$132 million (95% CI US$61.8–246.5 million). The cost per surgical human case was estimated at US$1,539. CE has a considerable economic impact on Iran, with the cost of the disease approximated at 0.03% of the country's gross domestic product. Establishment of a CE surveillance system and implementation of a control program are necessary to reduce the economic burden of CE on the country. Cost-benefit analysis of different control programs is recommended, incorporating present knowledge of the economic losses due to CE in Iran.
Author Summary
Cystic echinococcosis (CE), caused by the tapeworm Echinococcus granulosus, is a zoonotic infection that occurs worldwide. The adult parasite resides in the small intestines of dogs and the cyst form can develop in the liver and lungs of both humans and livestock. CE causes medical, veterinary, and economic losses in endemic areas. However, data on the economic consequences of CE are lacking. The present study estimated the monetary burden of CE in Iran. We used epidemiological and economic information to estimate direct and indirect costs of human and livestock CE in the country. Costs associated with human CE included the costs of surgery and hospital services in addition to lost wages due to work absenteeism during hospitalization and recovery. Costs associated with CE in livestock included losses due to condemnation of livers and lungs during carcass inspections, decreased carcass weight, reproductive losses, and reductions in milk and other animal products. We estimated the overall annual cost of CE in Iran at US$232.25 million, with the cost of the disease estimated to be approximately 0.03% of the country's gross domestic product. Implementation of a control program is necessary to reduce the economic burden of CE on Iran.
doi:10.1371/journal.pntd.0001915
PMCID: PMC3510083  PMID: 23209857
9.  The Global Burden of Alveolar Echinococcosis 
Background
Human alveolar echinococcosis (AE) is known to be common in certain rural communities in China whilst it is generally rare and sporadic elsewhere. The objective of this study was to provide a first estimate of the global incidence of this disease by country. The second objective was to estimate the global disease burden using age and gender stratified incidences and estimated life expectancy with the disease from previous results of survival analysis. Disability weights were suggested from previous burden studies on echinococcosis.
Methodology/Principal Findings
We undertook a detailed review of published literature and data from other sources. We were unable to make a standardised systematic review as the quality of the data was highly variable from different countries and hence if we had used uniform inclusion criteria many endemic areas lacking data would not have been included. Therefore we used evidence based stochastic techniques to model uncertainty and other modelling and estimating techniques, particularly in regions where data quality was poor. We were able to make an estimate of the annual global incidence of disease and annual disease burden using standard techniques for calculation of DALYs. Our studies suggest that there are approximately 18,235 (CIs 11,900–28,200) new cases of AE per annum globally with 16,629 (91%) occurring in China and 1,606 outside China. Most of these cases are in regions where there is little treatment available and therefore will be fatal cases. Based on using disability weights for hepatic carcinoma and estimated age and gender specific incidence we were able to calculate that AE results in a median of 666,434 DALYs per annum (CIs 331,000-1.3 million).
Conclusions/Significance
The global burden of AE is comparable to several diseases in the neglected tropical disease cluster and is likely to be one of the most important diseases in certain communities in rural China on the Tibetan plateau.
Author Summary
Human alveolar echinococcosis (AE), caused by the larval stage of the fox tapeworm Echinococcus multilocularis, is amongst the world's most dangerous zoonoses. Transmission to humans is by consumption of parasite eggs which are excreted in the faeces of the definitive hosts: foxes and, increasingly, dogs. Transmission can be through contact with the definitive host or indirectly through contamination of food or possibly water with parasite eggs. We made an intensive search of English, Russian, Chinese and other language databases. We targeted data which could give country specific incidence or prevalence of disease and searched for data from every country we believed to be endemic for AE. We also used data from other sources (often unpublished). From this information we were able to make an estimate of the annual global incidence of disease and disease burden using standard techniques for calculation of DALYs. Our studies suggest that AE results in a median of 18,235 cases globally with a burden of 666,433 DALYs per annum. This is the first estimate of the global burden of AE both in terms of global incidence and DALYs and demonstrates the burden of AE is comparable to several diseases in the neglected tropical disease cluster.
doi:10.1371/journal.pntd.0000722
PMCID: PMC2889826  PMID: 20582310
10.  Use of Recombinant Antigens To Detect Antibodies against Mycoplasma suis, with Correlation of Serological Results to Hematological Findings▿  
Clinical and Vaccine Immunology : CVI  2007;14(12):1616-1622.
Porcine eperythrozoonosis is a disease with worldwide distribution caused by the unculturable hemotrophic bacterium Mycoplasma suis. Current serological testing utilizes crude M. suis antigens purified from the blood of experimentally infected pigs. These antigens show high variability and are restricted to specialized laboratories. We evaluated a novel serological assay based on two recombinant M. suis antigens (rMSG1 and rHspA1). Antigen specificity was proven by means of sera raised against nonhemotrophic mycoplasma and other relevant bacteria. Using experimental and convalescent-phase sera, rMSG1 and rHspA1 enzyme-linked immunosorbent assays (ELISAs) demonstrated sensitivities, specificities, and predictive values (94.0 to 100.0%) equal to or higher than those of the M. suis whole-cell ELISA. Field samples from 120 weaning piglets grouped by quantitative PCR results were used to evaluate the diagnostic capability of the new ELISA systems in comparison to that of the whole-cell ELISA. Assuming a 100.0% specificity of the PCR, the whole-cell ELISA, rHspA1 ELISA, and rMSG1 ELISA showed specificities of 84.8%, 83.8%, and 90.6% and sensitivities of 61.5%, 74.0% and 58.1%, respectively. Cohen's kappa coefficients comparing the recombinant ELISAs to the whole-cell ELISA indicate moderate to substantial agreement. The detection of anti-MSG1 and/or anti-HspA1 antibodies in pigs was significantly correlated with decreased hematocrit, erythrocyte numbers, and hemoglobin concentrations, indicating that a single seropositive result is connected with clinical and etiological significance. In conclusion, rMSG1 and rHspA1 are sensitive and specific serological and infection markers which are for the first time used independently of animal experiments. They are especially fit to be used in routine diagnosis, pathogenesis studies, and large-scale epidemiological investigations.
doi:10.1128/CVI.00345-07
PMCID: PMC2168379  PMID: 17942612
11.  Human Alveolar Echinococcosis after Fox Population Increase, Switzerland 
Emerging Infectious Diseases  2007;13(6):878-882.
An increase in fox population has led to an increase in incidence of human alveolar echinococcosis.
We analyzed databases spanning 50 years, which included retrospective alveolar echinococcosis (AE) case-finding studies and databases of the 3 major centers for treatment of AE in Switzerland. A total of 494 cases were recorded. Annual incidence of AE per 100,000 population increased from 0.12– 0.15 during 1956–1992 and a mean of 0.10 during 1993–2000 to a mean of 0.26 during 2001–2005. Because the clinical stage of the disease did not change between observation periods, this increase cannot be explained by improved diagnosis. Swiss hunting statistics suggested that the fox population increased 4-fold from 1980 through 1995 and has persisted at these higher levels. Because the period between infection and development of clinical disease is long, the increase in the fox population and high Echinococcus multilocularis prevalence rates in foxes in rural and urban areas may have resulted in an emerging epidemic of AE 10–15 years later.
doi:10.3201/eid1306.061074
PMCID: PMC2792858  PMID: 17553227
Alveolar echinococcosis; Echinococcus multilocularis; epidemiology; fox (Vulpes vulpes); zoonosis; incidence; Switzerland; research
12.  In Vitro Metacestodicidal Activities of Genistein and Other Isoflavones against Echinococcus multilocularis and Echinococcus granulosus▿  
Antimicrobial Agents and Chemotherapy  2006;50(11):3770-3778.
Echinococcus multilocularis and Echinococcus granulosus metacestode infections in humans cause alveolar echinococcosis and cystic echinococcosis, respectively, in which metacestode development in visceral organs often results in particular organ failure. Further, cystic hydatidosis in farm animals causes severe economic losses. Although benzimidazole derivatives such as mebendazole and albendazole are being used as therapeutic agents, there is often no complete recovery after treatment. Hence, in searching for novel treatment options, we examined the in vitro efficacies of a number of isoflavones against Echinococcus metacestodes and protoscoleces. The most prominent isoflavone, genistein, exhibits significant metacestodicidal activity in vitro. However, genistein binds to the estrogen receptor and can thus induce estrogenic effects, which is a major concern during long-term chemotherapy. We have therefore investigated the activities of a number of synthetic genistein derivatives carrying a modified estrogen receptor binding site. One of these, Rm6423, induced dramatic breakdown of the structural integrity of the metacestode germinal layer of both species within 5 to 7 days of in vitro treatment. Further, examination of the culture medium revealed increased leakage of parasite proteins into the medium during treatment, but zymography demonstrated a decrease in the activity of metalloproteases. Moreover, two of the genistein derivatives, Rm6423 and Rm6426, induced considerable damage in E. granulosus protoscoleces, rendering them nonviable. These findings demonstrate that synthetic isoflavones exhibit distinct in vitro effects on Echinococcus metacestodes and protoscoleces, which could potentially be exploited further for the development of novel chemotherapeutical tools against larval-stage Echinococcus infection.
doi:10.1128/AAC.00578-06
PMCID: PMC1635224  PMID: 16954323
13.  Global Socioeconomic Impact of Cystic Echinococcosis 
Emerging Infectious Diseases  2006;12(2):296-303.
Because the human and economic losses of cystic echinococcosis are substantial, global prevention and control measures should be increased.
Cystic echinococcosis (CE) is an emerging zoonotic parasitic disease throughout the world. Human incidence and livestock prevalence data of CE were gathered from published literature and the Office International des Epizooties databases. Disability-adjusted life years (DALYs) and monetary losses, resulting from human and livestock CE, were calculated from recorded human and livestock cases. Alternative values, assuming substantial underreporting, are also reported. When no underreporting is assumed, the estimated human burden of disease is 285,407 (95% confidence interval [CI], 218,515–366,133) DALYs or an annual loss of US $193,529,740 (95% CI, $171,567,331–$217,773,513). When underreporting is accounted for, this amount rises to 1,009,662 (95% CI, 862,119–1,175,654) DALYs or US $763,980,979 (95% CI, $676,048,731–$857,982,275). An annual livestock production loss of at least US $141,605,195 (95% CI, $101,011,553–$183,422,465) and possibly up to US $2,190,132,464 (95% CI, $1,572,373,055–$2,951,409,989) is also estimated. This initial valuation demonstrates the necessity for increased monitoring and global control of CE.
doi:10.3201/eid1202.050499
PMCID: PMC3373106  PMID: 16494758
echinococcosis; cestodes; cost of illness; burden of illness; economics; zoonoses
14.  Dog ownership, dog behaviour and transmission of Echinococcus spp. in the Alay Valley, southern Kyrgyzstan 
Parasitology  2013;140(13):1674-1684.
SUMMARY
Echinococcosis is a re-emerging zoonotic disease in Kyrgyzstan, and the incidence of human infection has increased substantially since the collapse of the Soviet Union in 1991. Domestic dogs are hosts of Echinococcus spp. and play an important role in the transmission of these parasites. The demography, ecology and behaviour of dogs are therefore relevant in studying Echinococcus spp. transmission. Dog demographics, roles of dogs, dog movements and faecal environmental contamination were assessed in four rural communities in the Alay Valley, southern Kyrgyzstan. Arecoline purge data revealed for the first time that E. granulosus, E. canadensis and E. multilocularis were present in domestic dogs in the Alay Valley. Surveys revealed that many households had dogs and that dogs played various roles in the communities, as pets, guard dogs or sheep dogs. Almost all dogs were free to roam, and GPS data revealed that many moved outside their communities, thus being able to scavenge offal and consume rodents. Faecal environmental contamination was high, presenting a significant infection risk to the local communities.
doi:10.1017/S0031182013001182
PMCID: PMC3806042  PMID: 23985326
Echinococcus granulosus; Echinococcus canadensis; Echinococcus multilocularis; Kyrgyzstan; domestic dogs; demography; behaviour

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