Veterinary Parasitology

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1 Veterinary Parasitology 182 (2011) Contents lists available at ScienceDirect Veterinary Parasitology jo u rn al hom epa ge : The socioeconomic burden of parasitic zoonoses: Global trends Paul R. Torgerson a,, Calum N.L. Macpherson b a Division of Epidemiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland b St George s University, St George, Grenada, West Indies a r t i c l e i n f o Keywords: Disease burden, Parasitic zoonoses, Economics, DALY, Emerging diseases a b s t r a c t Diseases resulting from zoonotic transmission of parasites are common. Humans become infected through food, water, soil and close contact with animals. Most parasitic zoonoses are neglected diseases despite causing a considerable global burden of ill health in humans and having a substantial financial burden on livestock industries. This review aims to bring together the current data available on global burden estimates of parasitic zoonoses and indicate any changes in the trends of these diseases. There is a clear need of such information as interventions to control zoonoses are often in their animal hosts. The costs of such interventions together with animal health issues will drive the cost effectiveness of intervention strategies. What is apparent is that collectively, parasitic zoonoses probably have a similar human disease burden to any one of the big three human infectious diseases: malaria, tuberculosis or HIV in addition to animal health burden. Although the global burden for most parasitic zoonoses is not yet known, the major contributors to the global burden of parasitic zoonoses are toxoplasmosis, food borne trematode infections, cysticercosis, echinococcosis, leishmaniosis and zoonotic schistosomosis. In addition, diarrhoea resulting from zoonotic protozoa may have a significant impact Elsevier B.V. All rights reserved. 1. Introduction Of the nearly 1500 agents known to be infectious to humans, 66 are protozoa and 287 are helminths infectious agents, 66 are protozoa and 287 are helminths (Chomel, 2008; Taylor et al., 2001). The majority (60.3%) of emerging infectious diseases are zoonoses (Jones et al., 2008). Zoonoses represent a large burden of disease and there are changing patterns of disease burdens with disease emergence. Human population growth and socioeconomic changes result in the migration of populations into new ecological regions and changes in animal husbandry practices which can impact on disease emergence and disease burden (Macpherson, 2005). In addition improved diagnostics are demonstrating that many zoonoses have a higher burden then previously recognised. Some new syndromes Corresponding author. Tel.: address: paul.torgerson@access.uzh.ch (P.R. Torgerson). are also being attributed to parasitic zoonoses and hence add to the disease burden. Global warming may change the transmission dynamics of parasitic zoonoses in endemic areas and enable some parasites to transmit in regions where they were previously absent. 2. Disease burden and its calculation Disease burden is the impact of a disease on society measured by financial cost, mortality, morbidity, or other indicators. Calculating the total burden in monetary terms has the advantage that, with zoonoses, there may be substantial animal health losses and hence both the human and animal health losses can be calculated in one figure. For several diseases monetary costs have been defined and these are given where available. Monetary costs include loss of productivity in animals and treatment costs and loss of income in individuals affected by the disease. However, the absolute cost of treatment and convalescence of human patients is higher in high income countries than /$ see front matter 2011 Elsevier B.V. All rights reserved. doi: /j.vetpar

2 80 P.R. Torgerson, C.N.L. Macpherson / Veterinary Parasitology 182 (2011) in low income countries due to variations in medical and wage costs. Thus a disease in a wealthy country may have a higher financial burden than the same disease in a low income country even if it has a much higher incidence in the latter. These issues are discussed in greater detail in Carabin et al. (2005). Consequently, the World Health Organisation s preferred measure is the Disability Adjusted Life Year (DALY) and this was used to calculate the Global Burden of Disease (GBD) estimates (Lopez et al., 2006). This non-monetary measure avoids valuing human health differently in low and high income countries. It is a composite measure which takes into account the number of life years lost due to premature death (Years of Life Lost or YLLs) and the number of healthy life years lost due to living with a disability (Years Lived with Disability of YLDs). DALYs are calculated by summing the YLLs and YLDs. Diseases that result in a high mortality rate and/or high numbers of chronically disabled individuals will result in greater numbers of DALYs than acute diseases from which the patient generally makes a complete or almost complete recovery. Therefore human disease burden using this metric depends on both severity of the disease syndrome and the incidence. GBD has been reporting health information since 1990 (Stein et al., 2007). The GBD 1990 series (Murray and Lopez, 1996) constructed an internally consistent global overview of morbidity, disability, and mortality burden for some 130 diseases and conditions. This has been updated for 2001 (Lopez et al., 2006) and estimates are also available for 2004 with projections for 2008, 2015 and 2030 (WHO, 2008). However in GBD most zoonotic parasitic diseases were neither specifically included in the initial estimate nor in the updated series. The only parasitic diseases that have significant zoonotic transmission included were Leishmaniosis, Schistosomosis and Trypanosomosis (Chagas disease and African Trypanosomosis). Other parasitic zoonoses disappear as distinct entities, but the burden is included in other categories. For example, diarrhoeal diseases were calculated as a general category and some protozoan zoonoses will make a substantial contribution to the global burden of diarrhoeal disease. Since these publications of GBD, there have been estimates of the global or regional burden of some additional parasitic zoonoses. In addition a number of parasitic zoonoses are emergent or re-emergent and they present a substantial burden to the human population. It has also been suggested that DALY calculations may be inappropriate for calculating the burden of parasitic diseases (Payne et al., 2009) due to, inter alia, inappropriate or single disability weights for parasitic diseases when a variety of syndromes are present, problems of poly-parasitism or problems with missing data. Such issues are being or have been addressed using a variety of techniques including varying the disability weights and adopting stochastic techniques (see for example Budke et al., 2004; Fevre et al., 2008). Often the burden has been calculated in monetary terms rather than using the GBD approach and such data is available when DALYs may not be. In addition many parasitic zoonoses are neglected zoonoses so have not yet been considered by GBD. The problem of calculating human costs in DALYs and animal health costs in monetary losses is a significant one with zoonoses that affect both human and animal health. Monetarizing human health losses is one possible solution. A DALY is considered the equivalent of a loss of one year of healthy life and so the mean annual GDP per head in the country where the DALY was calculated may have some financial equivalence. But as previously discussed this would move away from one of the central ideas of the DALY which is to value human life equally and hence is unlikely to be accepted. Cost sharing between animal and human health sectors is an approach that has been proposed (Zinnstag et al., 2007) but still required monetary calculation of human health costs. This review will summarize the major trends in disease burden of parasitic zoonoses in both terms of monetary losses and DALYs where available. 3. Trends in the burden of cestode zoonoses 3.1. Larval cestode zoonoses Cystic echinococcosis Cystic echinococcosis (CE) in humans is caused by the larval stage of a number of taxonomically related species of Echinococcus: E. granulosus, E. ortleppi, E. intermedius and E. canadensis. These were, until recently, all considered to be strains of one species (E. granulosus), but following a taxonomic revision a number of species are now proposed (Thompson, 2008). All of these Echinococcus genotypes utilise canid, usually domestic dogs, as definitive hosts and a variety of ungulates, particularly farm animals as intermediate hosts. Man is generally an aberrant intermediate host in which the hydatid cyst develops, usually in the liver or lungs as a space occupying lesion, which can result in considerable morbidity (Eckert and Deplazes, 2004). As a result of a number of studies undertaken in recent years the societal burden of this disease is better known than many other parasitic zoonoses and updates are being undertaken in the GBD study. A preliminary estimate of the annual global burden of CE has suggested approximately 1 million DALYs are lost due to this disease (Budke et al., 2006). This is likely to be a substantial underestimate (Craig et al., 2007) (Table 1) with perhaps 1 million or more individuals currently suffering from CE globally. The global burden of CE, in terms of DALYs lost, suggests that CE may cause disability on at least a similar level to numerous better-known Neglected Tropical Diseases (NTD), including Chagas disease, dengue, onchocercosis, and African trypanosomosis. In addition the financial burden of CE on the global livestock industry is considerable with up to $2 billion lost annually. In Iceland, New Zealand, southern Cyprus and Tasmania the burden of CE is close to zero as a result of successful control or elimination programmes or due to high standards of veterinary public health that limit transmission to humans. These are islands which has facilitated elimination of the parasite. Some progress has also been made in Latin America to reduce human incidence of CE (Craig and Larrieu, 2006). Despite success in reducing this burden in some countries, much of Latin America remains highly endemic with particular problems in, for example parts of Peru (Gavidia et al., 2008). An economic assessment of the disease was under-

3 P.R. Torgerson, C.N.L. Macpherson / Veterinary Parasitology 182 (2011) Table 1 Possible magnitude of the annual global burden of parasitic zoonoses with that of the global burden of malaria, tuberculosis and HIV for comparison. Zoonosis Important aetiologies Possible Global Burden (DALYs) * Animal Health Costs Trends Zoonotic Schistosomosis Echinococcosis Schistosoma japonicum? Unknown Long term is decrease Assumes new disability weights Echinococcus US$ CE emergent in NIS, AE granulosus emergent in Europe E. multilocularis Cysticercosis Taenia solium T. saginata Very low Unknown Substantial animal health costs Toxoplasmosis Toxoplasma gondii Possibly substantial New sequaelae are being assigned to toxoplasmosis Food borne trematodes Fasciola spp. > Animal Fasciolosis is Increasing reports Opithorchis spp. very high Clonorchis spp. Paragonimus spp. Zoonotic Intestinal Giadia spp.? Unknown, but likely to protozoa Cryptosporidium spp. be high Vector born zoonotic Trypanosoma brucei protozoa rhodesiense T. cruzei Leishmania spp. Others Toxocara spp. Other nematodes > Burden due to Chagas disease is decreasing? 10 6 Control programmes for Trichinella are a large financial burden Assumes c 30% of epilepsy in low income countries due to neurocysticercosis Congenital and non congenital toxoplasmosis see text Estimated from GBD figures (WHO, 2008) Individually low human disease burden but collectively large The big three global infectious diseases Malaria HIV From the most current GBDdata (WHO, 2008) Tuberculosis * For most of these zoonoses, a global burden has yet to be published. The possible DALYs indicate a very crude estimate based on available data and serve only to illustrate the likely magnitude of the disease burden. taken in Uruguay (Torgerson et al., 2000) which suggested annual losses, including both animal and human health costs, of at least $2.9 million, and possibly as high as $22.1 million. However Uruguay is a country where control has made some progress in reducing the burden of CE, so the financial burden is now likely to be reduced. Generally in north America the human incidence is very low and consequently so is the human disease burden (Moro and Schantz, 2006). Sporadic cases of CE due to E. canadensis are seen mainly in indigenous people in northern Canada or Alaska (Rausch, 2003). Typically in central or Western Europe there is a tendency for decreasing numbers of autochthonous cases but increasing numbers recorded in immigrants. This is typified by a recent report from Austria (Schneider et al., 2010). There are important foci in southern Europe. In Spain CE annual costs of approximately EURO 133 million due human ill health and D 16 million to animal health losses (Benner et al., 2010). In the Italian islands of Sicily or Sardinia prevalences in sheep of 67% and 75% respectively and high human incidence rates of 2.3 and 6.6 per 100,000 per annum respectively have been recorded. On the Italian mainland there are also focal hotspots of CE in north, central and southern Italy (Garippa and Manfredi, 2009). In Greece a decline in the ultrasound prevalence (the prevalence recorded by ultrasound scanning in a cross sectional study of the population) in human patients now being seen in some areas (Varbobitis et al., 2010), probably attributable to a national control programme. In northern Europe there is generally a low or negligible burden of autochthonous CE. The UK has an endemic focus, mainly in Wales and is believed to result in economic losses of greater than $1 million per annum (Torgerson and Dowling, 2001). A control campaign in Wales was abandoned in the 1990s and there is some evidence that CE may be re-emerging in Wales (Buishi et al., 2005). In most countries of the former Soviet Union and Eastern Europe there have been considerable increases in human CE since the early 1990s with reported cases, and hence burden, approximately four fold higher than during communist administration. This is due to the abandonment of large collectivised farming systems and the neglect or collapse of veterinary public health services (Todorov and Boeva, 1999; Torgerson et al., 2006). In many areas of the world there is a persistently high burden of CE, which has become better documented in recent years. In China CE affects large parts of the Tibetan plateau and western regions of the country. In some districts of western Sichuan for example, perhaps 6% or more of some rural populations have evidence of cysts through ultrasound examination (Tiaoying et al., 2005). Similar proportions are also infected with alveolar echinococcosis (AE) and over the population as a whole echinococcosis has a life time burden of 0.81 DALYs per person (Budke et al., 2004) making it amongst the leading causes of morbidity in these regions. The other highly endemic region is Xingjiang and there are also many cases reported from inner Mongolia (Zhenghuan et al., 2008). It has been estimated that China has approximately 40% of the global burden of CE (Budke et al., 2006), with nearly 350,000 individuals living with the disease (Craig et al., 2007).

4 82 P.R. Torgerson, C.N.L. Macpherson / Veterinary Parasitology 182 (2011) Elsewhere in Asia there are large numbers of CE cases in parts of Russia, most of central Asia, Iran and Turkey. CE is also common in the Middle East and North Africa. The annual incidences vary between 1 and 27 cases per 100,000 with most being in the 5 10 cases per 100,000 ranges. Estimates of close to half a million people across this endemic area living with CE have been made (Craig et al., 2007). Economic evaluations have been undertaken in Tunisia (Majorowski et al., 2005) and Jordan (Torgerson et al., 2001) which indicate that echinococcosis represents a substantial economic effect in relation to the respective countries GDP perhaps up to 0.5% of total economic activity for these countries. In Turkey production losses due to CE in livestock have been estimated at $89 million per annum (Sariozkan and Yalcin, 2009). In sub-saharan Africa a notable endemic area is the Turkana region in northern Kenya. Here incidences are amongst the highest in the world (Magambo et al., 2006). In northern Ethiopia a recent study suggested that 22% of cattle have hydatid cysts resulting in the equivalent of US$1.56 loss per animal due to condemnation and production losses (Kebede et al., 2009b). A similar study suggested that the prevalence in some regions approaches 50% with the direct and indirect losses of $21 per infected animal (Kebede et al., 2009a). Elsewhere in Ethiopia prevalences in cattle and sheep of 47% and 29% respectively have been reported (Getaw et al., 2010) Alveolar echinococcosis Human alveolar echinococcosis (AE) is caused by the larval stage of the fox tapeworm Echinococcus multilocularis and is distributed through much of the northern hemisphere. The global burden of AE has recently been estimated at over 600,000 DALYs per annum (Torgerson et al., 2010). This is comparable to several of the diseases in the neglected tropical disease cluster (trypanosomosis, Chagas disease, schistosomosis, leishmaniosis, lymphatic filariasis, onchocercosis, intesinal nematode infections, Japanese encephalitis, dengue, and leprosy) (Mathers et al., 2007) Over 90% of the global burden of AE is in China on the Tibetan Plateau. In certain communities there may be as many as 5 10% of the population infected by AE and the annual incidence of new cases possibly exceeded 16,000 in this region (Torgerson et al., 2010). Dogs have a high prevalence of infection with E. multilocularis (Budke et al., 2005) and are likely to be the important source of infection for humans. Landscape change, often associated with overgrazing, appears to have altered the small mammalian fauna on the Tibetan plateau and hence promoting transmission in both the fox-small mammal cycle and the anthropomorphic cycle involving dogs (Wang et al., 2004, 2006a). Elsewhere in Asia there are important foci in Turkey and sporadic cases in Iraq, Iran, Afghanistan and India (Torgerson et al., 2010). On the Japanese island of Hokkaido there are perhaps 10 or so human cases per year (Ito et al., 2003). In the former Soviet Union and Eastern European there may be over 1000 cases per year (Torgerson et al., 2010). In Kazakhstan and Kyrgyzstan there have been high prevalences of infection recorded in dogs (Stefanic et al., 2004; Ziadinov et al., 2008) and a very high intensity of infection in foxes (Ziadinov et al., 2010), but there has not yet been a major epidemic in humans (Torgerson et al., 2009). However as there are clearly high levels of transmission of CE resulting from dog contact in these countries, it is possible that increased reports of AE may occur in the future In Europe increasing fox populations have been associated with an increase in AE incidence in Switzerland (Schweiger et al., 2007). However, the actual burden of disease due to AE has almost certainly been reduced due to better case management and hence improved prognosis in recent years (Torgerson et al., 2008). The UK presently appears to be free of E. multilocularis although there is believed to be a high probability of introduction through infected dogs if the requirement for praziquantel treatment of dogs prior to UK importation is abandoned which may occur as a consequence of EU regulations (Torgerson and Craig, 2009). Introduction to new areas is always a major concern and this is demonstrated by the recent detection of two infected foxes in Sweden, a country previously thought to free of E. multilocularis (Osterman et al., 2011) In North America human AE is very rarely seen, despite the parasite being endemic over large parts of the mid western USA, Canada and Alaska. In some isolated Native American communities in Alaska substantial numbers of cases have been recorded in the past, possibly associated with dog infections and an anthropomorphic cycle. These outbreaks have now been controlled by successful intervention (Rausch et al., 1990; Schantz et al., 1991) Other forms of echinococcosis Echinococcus oligarthrus and E. vogeli are confined to the New World. Either species is capable of causing echinococcosis in humans (often referred to as neotropical echinococcosis). Disease due to E. vogeli is similar to AE and is characterized by aggressive infiltrative growth and external budding, whereas infection with E. oligarthrus has a more benign course. Compared to other Echinococcus species, human echinococcosis caused by these two species is relatively rare. Up to March 2007 a total of 172 cases of human neotropical echinococcosis had been documented (D Alessandro and Rausch, 2008). However there is some evidence that this incidence may be increasing albeit from a low base (Tappe et al., 2008) Cysticercosis Taenia solium has a global distribution but is rare or absent in high income countries and in countries where pork is not consumed. The main endemic regions include Latin America, China, South East Asia and sub-saharan Africa. Presently the global burden of cysticercosis is unknown, but some local studies have been completed. In west Cameroon epilepsy associated with neurocysticercosis is believed to result in approximately 45,800 DALYs or 9 per 1000 persons with a possible economic burden amongst the same population of over D 16 million (Praet et al., 2009). In the eastern cape of South Africa the annual monetary burden of cysticercosis has been estimated at between US$18.6 million and US $34.2 million (Carabin et al., 2006). Perhaps a good indication that the global burden of cysticercosis is likely to be considerable comes

5 P.R. Torgerson, C.N.L. Macpherson / Veterinary Parasitology 182 (2011) from the results of a systematic review on the association of epilepsy and neurocysticercosis (Ndimubanzi et al., 2010). This study suggests that in low or middle income endemic countries approximately 30% of epilepsy may be attributable to neurocysticercosis. The global burden of epilepsy estimated is to be 7.8 million DALYS. Of these, 6.5 million DALYs occur in Sub Saharan Africa, Latin America, South Asia and the Western Pacific (including China): regions where T. solium is highly endemic. It is also interesting to note that the proportion of the total burden of disease caused by epilepsy in the Middle East and North Africa, middle income countries where pork consumption is very low, is 0.378%: comparable to that of high income countries (0.314%) where T. solium has largely been eliminated. In Latin America, middle income countries but with high pork consumption, the proportion of the total disease burden attributable to epilepsy is 0.707% (calculations from data in (Lopez et al., 2006). Thus an estimate of over 2 million DALYs per annum (Table 1) would not be unreasonable, although the actual global burden is still unknown. The future trends on the burden of T. solium cysticercosis will depend on patterns of pork consumption, the success of veterinary public health interventions and economic growth. Pork consumption is increasing in countries such as China (Ortega et al., 2009), but rapid economic development should also promote veterinary public health programmes to control this parasite. Human cysticercosis, dracunculiasis and lymphatic filariasis are the only human parasitic diseases that have the potential to be eradicated globally (Molyneux et al., 2004). Therefore with effective investment in veterinary public health it may be possible to eventually reduce the global burden of cysticercosis to zero, although in some regions (such as sub-saharan Africa) cysticercosis will remain problematic for the foreseeable future Other larval cestodoses Human coenurosis caused by the larvae of Taenia multiceps, T. serialis or T. brauni are sporadically recorded in the literature. CNS infection can be devastating and hence result in a high disability weight. As reports of such infections are rare, the global burden of human coenurosis is likely to be very low Adult cestode zoonoses Taeniosis Human infection with adult Taenia occurs through ingestion of undercooked pork or beef. When man is the definitive host of these parasites, the clinical signs are moderate and hence the burden will be negligible in terms of DALYs (although individuals infected with intestinal T. solium are at high risk of being affected by cysticercosis with the attendant health effects). There are considerable economic effects as pork and beef containing cysticerci are condemned to prevent human infection. Even when infections rates in animals are very low, the economic impact can still be significant. In Iran where about 0.02% of cattle carcasses are condemned due to T. saginata cysticercosis, the annual economic losses are in the order of $400,000 (Jahed Khaniki et al., 2010). In highly endemic areas, such as many parts of Africa, prevalences are typically greater than 20% (Abunna et al., 2007; Opara et al., 2006) Diphyllobothriosis Diphyllobothrium latum has a circum polar distribution in northern temperate and sub arctic countries. The parasite infects an estimated 9 to 20 million people (Lloyd, 2011). Infections have also been described in some South American countries and sporadically elsewhere. Many human infections are asymptomatic, but abdominal pain, dizziness, fatigue, transient diarrhoea, dyspepsia, and vomiting may occur. Classically, pernicious anaemia may occur due to uptake of vitamin B 12 by D. latum and the dissociation of B 12 and intrinsic factor. Improved sanitation and treatment of effluents to remove eggs are being achieved at many rivers and lakes and this may help to decrease prevalence. D. latum tapeworms also infect piscivorous domestic (dog and cat) and wild life (bear, fox) reservoir hosts. The increasing popularity of eating raw or undercooked fish may lead to an increase in human dyphyllobothrioisis. The burden of diphyllobothriosis is likely to be low despite many human infections as the disability weight would generally be close to zero except in the small numbers of cases that may suffer from anaemia Other adult cestodoses Hymenolepis spp. are fairly commonly found in humans with perhaps over 50 million global infections for H. nana. H. nana can establish in humans without an intermediate host or can be transferred from rodents. For other Hymenolepis spp. an intermediate host is obligatory. Generally human Hymenolepis infections are asymptomatic, but heavy infections can result in abdominal pain, diarrhoea, poor weight gain, eosinophilia, nausea, vomiting and uticaria. Other adult cestodes include Dypiledium caninum, Bertiella spp., Mesocestoides spp. and Raillietina spp. have been occasionally recorded in humans. As these infections are rare and intestinal cestode infections are generally of low pathogenicity, the socioeconomic burden is likely to be very low 4. Trends in the burden of trematode zoonoses 4.1. Food-borne trematode zoonoses There are more than 80 species of food-borne trematodes of which Fasciola spp., Clonorchis sinensis, Opisthorchis spp., Fasciolopsis buski, Paragonimus spp., and to a lesser extent Heterophyes spp. and Metagonimus spp. are of public health importance. Of the estimated one billion people at risk of infection (Keiser and Utzinger, 2005) up to nine million may suffer from symptomatic sequelae and between 10,000 to 11,000 people die each year (WHO, 1998b). Thus an annual global burden of over 500,000 DALYs would not be an unreasonable expectation (Table 1) although more precise estimates are presently unavailable The foodborne trematode zoonoses are transmitted by ingestion of metacercariae and are perpetuated through inadequate sanitation, cultural and evolving food habits, growth of aquaculture and by a wide range of domestic and wild definitive hosts. The DALY s contributed by the food-borne

6 84 P.R. Torgerson, C.N.L. Macpherson / Veterinary Parasitology 182 (2011) trematodes have yet to be calculated but taken as a whole are likely to be substantial and their importance is increasingly being recognized Fasciolosis Fasciolosis is an important disease of livestock and humans caused by species of the genus Fasciola. Fasciola hepatica is responsible for the disease in temperate climates whereas F. gigantica is found in tropical areas. Fasciola spp. is a true zoonosis being predominantly a parasite maintained by infected sheep and cattle that can be transmitted to humans. Humans may also maintain infection as definitive hosts (Esteban et al., 1999). Other domestic animals, such as pigs, goats, dogs, alpacas, llamas and also rats can serve as definitive hosts. The snail Galba truncatula (formerly Lymnaea truncatula) is a well recognized intermediate host although other snail species may be important locally. Transmission to the definitive host is by the ingestion of metacercaria, either food-borne through ingesting raw contaminated aquatic plants or water-borne by drinking contaminated water (Esteban et al., 2002). Risk factors associated with infection include age with most infections in children. There is also a correlation between human and animal prevalence in the same region (Parkinson et al., 2007). An estimated 2.4 million people in over 61 countries are infected annually with Fasciola spp. with 180 million at risk of infection (Haseeb et al., 2002; Mas-Coma et al., 1998). Fasciola spp. endemicity is highest in Bolivia, Peru, Cuba, Iran, and Egypt with significant prevalence occurring in Asia, Africa and a number of European countries. The true extent of fasciolosis is unknown with large epidemiological studies having only been carried out in Egypt (Curtale et al., 2005) and Bolivia (Esteban et al., 2002; Parkinson et al., 2007). Fasciolosis is rarely fatal in humans and the major pathology results from hemorrhaging and inflammation of the liver caused by trapped or migrating flukes (Aksoy et al., 2005). The extent of this pathology is dependent upon the number of flukes that invade the liver. Flukes that reach the bile ducts cause significant pathology through the thickening and dilation of the bile ducts and gallbladder. Blood loss, particularly in the acute phase of infection, results in anaemia. Similar clinical manifestations occur in animals. Fasciolosis also impacts a major burden on the livestock industries with substantial effects on productivity. Many endemic countries have high livestock prevalences often with more than 50% of animals infected (Torgerson and Claxton, 1999). In Switzerland, which has a population of 1.6 million cattle the annual economic losses have been estimated at D 52 million (Schweizer et al., 2005) based on a mean prevalence of bovine fasciolosis of 10.9% Fish-borne trematodes A large number of different trematode genera and species result in millions of fish-borne human infections annually (reviewed by Lloyd and Soulsby, 2011). Many of these zoonotic trematode infections occur in Asia but some are more widespread. Humans may be important or occasional definitive host acquiring infection from eating raw/undercooked fish. Adult fish-borne trematodes occur in the biliary system or intestine: occasionally ectopic sides are also reported. The global burden of fish borne trematodes is presently being estimated and is likely to be considerable due to high human incidences and severe morbidity and high fatalities resulting from chronic sequelae. Clonorchis sinensis, Opisthorchis viverrini and O. felineus are parasites of fish-eating mammals, particularly in Asia and Europe where more than 20 million people are infected. In highly endemic areas, such as north-east Thailand, the prevalence of O. viverrini may reach up to 90% (Brockelman et al., 1987). Clonorchis sinensis is prevalent in China, Taipei, Vietnam, Japan and Korea. The main animal hosts are cats, dogs, pigs, camels and rats. Most light infections, including light chronic infections (the flukes can live for up to 15 years), are usually asymptomatic but moderately infected individuals may experience fever, fatigue, rash and gastrointestinal complaints. These symptoms may be exacerbated in patients with heavy (patients passing > 10,000 eggs per gram of faeces) and long standing heavy infections. Such patients can also experience cholestasis, recurrent pyogenic cholangitis, cholecystitis, biliary and liver abscess, biliary and liver cirrhosis, pancreatitis, and hepatitis. The most severe consequence is cholangiocarcinoma. The mechanism of carcinogenesis remains arcane but irritation caused by the fluke plays a crucial role. The International Agency for Research on Cancer upgraded C. sinensis from a probable carcinogen (group 2A) to a definite carcinogen (group 1) (Bouvard et al., 2009). Patients developing cholangiocarcinoma have a poor prognoses and most die within a year of diagnosis even when sophisticated treatment is applied (Yalcin, 2004) Opisthorchis felineus is prevalent in Poland, eastern Germany and in parts of the former USSR. The adult flukes live in the bile ducts and can occur in large numbers. Infection occurs through eating fish and the metacercariae reach the liver by direct migration up the bile duct. Clinical manifestations are rare, but infection increases the risk of cholangiocarcinoma (Haswell-Elkins et al., 1994). O. viverrini is categorized as a definite carcinogen (group 1) whereas O. felineus is not (Bouvard et al., 2009). Heterophyes heterophyes and Metagonimus yokogawai are probably the two most important of numerous different species of small (usually <2.5 mm), zoonotic intestinal flukes found in mammals and birds which ingest fish. These flukes commonly occur in Japan, Laos, Thailand, the Republic of Korea, Hawaii, the Balkans, the Philippines, China, Taipei, Turkey and Siberia. Clinical manifestations are rare and, if present, are usually due to eggs trapped in various tissues. Echinostoma ilocanum, E. revolutum, E. malayanum, E. echinatum and E. hortense are of minor zoonotic importance but a high prevalence has been reported in endemic countries, such as the Republic of Korea, the Philippines, Indonesia, Malaysia and Thailand. Heavy infections may result in diarrhoea, anorexia and abdominal discomfort. Control of all fish-borne trematode zoonoses is similar and can be achieved through treatment with praziquantel, sanitation measures and education to discourage consumption of raw fish.

7 P.R. Torgerson, C.N.L. Macpherson / Veterinary Parasitology 182 (2011) Paragonimosis is an important food-borne trematode zoonosis due infection by numerous species of lungdwelling flukes. Over 20 million people are infected world-wide through eating raw or undercooked crabs, crayfish or shrimp. Infection may also occur when paratenic hosts, such as wild boar are consumed. Paragonimus westermani, is the main species in the Far East, P. miyazakii, P. skryjabini and P. heterotrema in Asia, P. africanus and P. uterobilateralis in Africa and P. mexicanus and other species occur in Latin America. Countries with significant numbers of cases include China, Taipei China, Thailand, Japan, Nigeria, Cameroon, Peru and Ecuador. Numerous species of mammals may act as definitive hosts, including dogs, cats and wild carnivores. Pulmonary infection is characterised by a chronic productive cough and chest pain. Neurological infections have been reported from the Far East, especially the Republic of Korea. CT scans are useful for disclosing brain lesions Schistosomosis Of the 18 Schistosoma spp., five infect humans and three, S. japonicum, S. mansoni and S, mekongi are zoonotic. The importance of the animal definitive hosts, baboons (Legesse and Erko, 2004) and rodents (Duplantier and Sene, 2000) in Africa for S. mansoni and pigs in Laos and Cambodia for S. mekongi (Strandgaard et al., 2001) is unclear. S. japonicum has a wide range of definitive hosts. Studies in the marshlands and lake region of the Yanze river basin, where the majority of human cases of S. japonicum in China occur, demonstrated that water buffaloes and cattle contributed significantly more to human infection than other domestic animals, such as dogs, cats, pigs, sheep and goats (Wang et al., 2006b). In contrast rodents and dogs have been suggested as the most important reservoir hosts in some of the hilly/mountainous regions of China, where bovines are scarce and human infections are not as common (McManus et al., 2010; Rudge et al., 2009). In the Philippines dogs are thought to be important definitive hosts (Rudge et al., 2008). Worldwide an estimated 207 million people are infected with schistosomosis (Steinmann et al., 2006). An initial DALY estimate for schistosomosis of million has been recently reassessed. Most zoonotic cases of schistosomosis are due to S. japonicum. New disability weights given to S. japonicum (Finkelstein et al., 2008) and update information on global prevalence (van der Werf et al., 2003) have been used. These studies indicate that the true burden of human schistosomosis is substantially higher and is currently estimated to be approximately 70 million DALYs annually (Hotez and Fenwick, 2009; King and Dangerfield- Cha, 2008). This burden estimate exceeds that for malaria or TB and almost equates to the DALYs lost from HIV/AIDS. The DALY s contributed by the zoonotic schistosomes will be less. But even if only 14% of global schistosomosis is zoonotic in origin, it would push the global burden of zoonotic schistosomosis to over 10 million DALYs annually (Table 1). S. japonicum additionally debilitates infected domestic livestock which are used for food and as work animals. Economic losses for infections in livestock have been seldom studied and hence are less defined but add significantly to the economic burden and suffering of communities. It is known that S. bovis (a non zoonotic species) can result in substantial economic losses in livestock (Hunt McCauley et al., 1984) and hence, by analogy, direct production losses due to S. japonicum are likely. Schistosomosis is strongly linked with poverty, and despite recent improvements in the rural Chinese economy, which have resulted in a better standard of living, the prevalence of S. japonicum and its associated morbidity have continued to rise in some localities. The downturn in the global economy in 2007 resulted in the closure of businesses in urban areas, employment opportunities contracted and millions of city residents returned to their former rural villages: some of which were located in S. japonicum endemic areas (McManus et al., 2010). S. japonicum currently is an important zoonosis in five provinces in China where more than 50 million people are at risk and approximately one million people and several hundred thousand livestock are infected (McManus et al., 2010). S. japonicum also occurs in 28 provinces in the Philippines and in discrete foci in the province of central Sulawesi in Indonesia (King, 2009). Water resource development, including irrigation and the construction of dams for water conservation, hydroelectric power generation etc. in schistosomosis endemic areas, such as the Gezira-Managil dam in Sudan, the Aswan dam in Egypt, the Melkasadi dam in Ethiopia, the Kariba dam in Zimbabwe and the Danling and Huangshi dams in China have resulted in an increase in prevalence or reemergence of the disease in those countries (Gryseels et al., 2006; Steinmann et al., 2006). The recently completed Three Gorges dam in China which has endemic S. japonicum foci above and below the dam is anticipated to have an impact on the parasite increasing its current distribution and intensity (McManus et al., 2010). As with other water development projects it is anticipated that this will occur through habitat alteration favoring increased snail breeding sites, increased grazing areas for important reservoir hosts, occupational factors and an increase in the susceptible human population attracted to migrate to the endemic areas from non-endemic regions of the country. Availability and use of latrines influences the importance of humans in contaminating the environment and their importance vis a vis domestic and wild definitive hosts in maintaining transmission. S. japonicum was successfully eliminated from Japan through snail control and socioeconomic changes. The national schistosomosis control program in China is recognized as one of the most successful globally: the cornerstone of the programme being mass chemotherapy. Spatial epidemiological methods using geographical information systems (GIS), remote sensing (RS), incorporated with advanced Bayesian based spatial statistics have been important tools for identifying high-risk areas for S. japonicum transmission for China s control programme (Yang et al., 2005). However, recent control successes appear to be stalling. Together with the potential for its reemergence S. japonicum is regarded by the Chinese authorities as being on par with HIV/AIDS, TB and hepatitis B as a public health problem (Wang et al., 2008). A recent trial carried out in two villages where in one all humans and

8 86 P.R. Torgerson, C.N.L. Macpherson / Veterinary Parasitology 182 (2011) water buffaloes were treated with praziquantel and the other village where only humans were treated showed that chemotherapy given to water buffalo reduced human incidence. Mathematical models supported this conclusion and predicted that water buffaloes were responsible for an aetiological fraction of 75% of human Schistosomosis in this setting (Williams et al., 2002). Thus an integrated approach to control needs to be implemented, supported strongly by mathematical models. It has been proposed that such integrated control will incorporate the use of human and bovine chemotherapy, anti-infection and anti-fecundity DNA vaccine constructs for water buffaloes (still under development), health education/promotion, improved sanitation and focal use of molluskicides (Wang et al., 2009). Control of zoonotic Schistosoma species provides a serious challenge but successes already achieved show that it can be achieved. 5. Trends in the burden of nematode zoonoses 5.1. Ascaroses Toxocarosis Toxocarosis due to the zoonotic helminth, Toxocara canis, can present as a number of syndromes including covert toxocariasis, neurological toxocarosis, visceral lava migrans (VLM) and ocular larva migrans (OLM). The parasite has a global distribution and human infection is acquired by the ingestion of embryonated eggs of T. canis passed by dogs (puppies in particular) and foxes and also probably to a lesser extent by the ingestion of T. cati eggs passed by cats. Other species potentially zoonotic include Toxocara vitulorum and Toxocara pteropodis. Humans are accidental or paratenic hosts, in which L2 larvae maturation is inhibited and clinical syndromes are thought to be related to infection dose and frequency and to the migratory habits of the L2 larvae. Most cases of Toxocara infection are asymptomatic but some result in a variety of syndromes mediated mainly through a generalized antibody and inflammatory response. VLM a syndrome which is primarily diagnosed in young children, may last for weeks or months and exhibits as inflammation of internal organs and sometimes the central nervous system. Patients can present with fever, cough, asthma, abdominal pain, nausea, fatigue, weight loss, anorexia, headache, rash, and vomiting. In rare cases, epilepsy, pleural effusion, respiratory failure, and death have been reported. OLM is rare compared with VLM, is usually unilocular and is caused by the migration of a single larva in the orbit. A gradual and permanent visual impairment occurs over days or weeks depending on the location of the larvae, the eosinophilic and later the fibrotic granulomatous response: blindness occurs in many cases. Covert toxocarosis is characterised by chronic coughing, fever, abdominal pain, headaches and changes in behavior. Covert toxocarosis, has also been associated with asthma and may be linked to the rise in asthma observed in inner city children in the US (Busse and Mitchell, 2007), as well as impaired cognitive development (Stewart et al., 2005). Neurotoxocarosis is rare with patients presenting with seizures, headaches and other neurological symptoms. Seroprevalence rates have been examined in a few countries and vary from 2% to 14% in industrialised nations with high risk groups having much higher prevalence, to over 80% in the tropics (Smith and Noordin, 2006). Children are most at risk in all parts of the world but increasingly adults are being diagnosed in greater number as a result of meat-borne infection. In the US a recent national seroprevalence and risk factor study involving more than 30,000 people demonstrated a prevalence of 13%. Infection was associated with the level of education of the head of household, with poverty, ethnicity and dog ownership (Won et al., 2008). The costs associated with diagnosis, which is problematic, and treatment for this zoonosis are considerable. Given the widespread distribution and high frequency of this mainly childhood zoonosis, where in the US, for example, between 1.3 and 2.8 million people are infected (Hotez, 2008) toxocarosis poses an important burden on society and at the individual level. Toxocarosis along with other helminths, strongyloidiosis, ascariasis, and cysticercosis are regarded as one of the neglected diseases of poverty in the US as the infection disproportionately affect impoverished populations (Hotez, 2008). The DALY contribution is likely to be fairly high but the lack of data, particularly source attribution data of the often vague non specific symptoms makes the importance difficult to quantify. The monetary and non-monetary methods by which the burden of toxocarosis and hence the benefits of control have been discussed (Torgerson and Budke, 2006) Anisakiosis Anisakiosis is a food-borne nematode zoonosis resulting from ingesting the L3 larval stage of Anisakis simplex, A. physeteris and Pseudoteranova decipiens in marine fish, squid or eels which serve as the second intermediate hosts. Clinical anisakiosis may be acute or chronic developing after the penetration of the larvae into the mucosal wall of the alimentary tract. The affected sites undergo erosion, ulceration, swelling, inflammation, and granuloma formation around the larvae. Patients present with acute abdominal pain, indigestion, nausea, vomiting, and occasionally with allergic hypersensitive reactions. Such reactions vary from isolated angioedema to urticaria and life threatening anaphylactic shock. Generalized symptoms can be divided into gastric anisakiosis, which may resemble peptic ulcer or gastric cancer, or intestinal anisakiosis resembling appendicitis or peritonitis. Anisakiosis, first described in the 1960s has become more frequently reported especially in eastern Asia (mostly Japan) and Western Europe where large quantities of raw marine fish are consumed (Chai et al., 2005). Improved diagnostic tests increasingly demonstrate that this is a worldwide zoonosis and today approximately 2000 new cases are reported annually (Chai et al., 2005). Because of the sometimes severe symptoms, chronic nature of some infections and potential fatal cases, the disease burden could be significant. However, the difficulties of making a diagnosis make it a challenge to accurately assess this burden as the non specific clinical signs could be attributable to other diseases.

9 P.R. Torgerson, C.N.L. Macpherson / Veterinary Parasitology 182 (2011) Other ascarid species Toxascaris (dogs, cats), Ascaris sum (pigs), Lagochilascaris (opossums), Porrocaecum (birds of prey), Ophidascaris, Polydelphis, Travassoascaris (snakes), etc., can infect humans, but any role is probably limited through short migratory times or lack of human contact with eggs. Baylisascaris procyonis (raccoons) L2 larvae migrate aggressively, pathology is severe and although rare this species is frequently fatal increasing its zoonotic importance (Lloyd and Morgan, 2011). The incidence of this disease is extremely low, so consequently the burden of disease will also be low Trichinellosis Trichinellosis is a global helminth zoonosis, which occurs when culturally distinct food habits include the consumption of raw or improperly cooked meat or meat products. Meat from pigs is the commonest source of human infection; occasionally horses, fed pork products are involved, and meat from a wide range of wildlife species. Trichinella spp. consist of two clades: encapsulated and non encapsulated (Pozio and Darwin Murrell, 2006). The encapsulated clade comprises five species and four genotypes whilst the non-encapsulated clade comprises one species infecting mammals and birds, and two species infecting mammals and reptiles. T. spiralis is the only species that normally occurs in domestic animals whilst all the other species are primarily parasites of wildlife and. have been reported from approximately 150 animal species. Trichinella species can be transmitted either from the sylvatic environment to the domestic one or from domestic animals to wildlife. Human cases of trichinellosis have been documented in 55 countries. The incidence of clinical trichinellosis is unknown but it has been estimated that approximately 10,000 cases occur annually with 0.2% of these cases being fatal (Pozio, 2011). The acute nature of the disease and small numbers of fatalities will result in a low global burden of disease. The low incidence is due in part to good pig farming practices legislatively enforced in most developed and some developing countries. The risk of outbreaks, however, remains Strongyloidosis Strongylodiosis, caused by Strongyloides stercoralis, is a soil-transmitted helminth infection where humans, primates and dogs serve as definitive hosts. The parasite is found in tropical and some temperate areas of the world where poor sanitation and low socioeconomic conditions prevail. S. stercoralis is unique amongst zoonotic nematodes, in that larvae passed in faeces can give rise to free-living generations of adults and subsequently more infective larvae. The parasite is also able to replicate within the host (autoinfection) as the female is viviparous and thus infections can persist for many decades. Human infection is usually asymptomatic but clinical cases are associated with chronic enteritis, eosinophilia, malabsorption syndrome and impaired child development. Hyperinfection can occur in some patients and an association with those who have HTLV-1 infection or who are on corticosteroids has been demonstrated giving rise to a syndrome, known as disseminated strongyloidosis. Such infections are nearly always fatal. The degree to which zoonotic transmission occurs is uncertain though primate and dog- parasite clades have been described (Hasegawa et al., 2010). Further studies are required to elucidate the importance of dogs and humans in perpetuating transmission. Strongyloidosis occurs all over the tropics and subtropics and in found in varying prevalences in both developed and industrialized countries. Difficulties in diagnosis and the variability of prevalence within a country coupled to the parasites longevity in infected hosts has resulted in estimates on the numbers infected globally from as low as 3 million to over 100 million (Nolan et al., 2011). S. stercoralis is recognised as a neglected disease of poverty in the US where 68,000 to 110,000 individuals are infected (Hotez, 2008). The burden from this parasitic disease is uncertain but may be considerable, particularly since impaired child development will result in considerable numbers of YLDs associated with infection. The proportion of this burden that is from animal sources is likewise uncertain Angiostrongylosis Angiostrongylus cantonensis is an emerging zoonosis with the first human cases being reported in 1945 and thereafter cases were only sporadically reported essentially until the 1990s. In the last few decades human cases have been reported from endemic areas including a number of Pacific island nations and Asia (Thailand, Taiwan, China, Vietnam, Malaysia, Cambodia) to more recently described foci in the US, Caribbean, Japan, Indonesia, New Zealand and Australia. Worldwide more than 2800 cases of human angiostrongylosis have been reported from over 30 countries (Wang and Lun, 2011). Human infection results from eating infected raw or undercooked land or aquatic snails (the primary intermediate host species), slugs or paratenic hosts such as prawns and land crabs, predacious land planarians, freshwater fish, frogs, toads or monitor lizards and in endemic areas from unwashed contaminated vegetables. The geographical expansion of the parasites range has been facilitated by the unintended introduction of infected definitive hosts such as numerous species of rats. Establishment of the parasite has also been facilitated by the intended or accidental introduction of snail intermediate host species. Clinically humans present with a range of symptoms from mild to eosinophilic meningitis and in extreme cases such infections have been fatal. The average patient is ill for two weeks but the condition can last for months. Although the DALY s for this zoonosis is currently low it is increasing as the parasite spreads geographically Dirofilariosis A number of species of Dirofilaria (including D. immitis, D. repens, D. roemeri, D. tenuis, D. ursi, D. striata, D. subdermata, D. magnilarvatum and D. corynodes) have been known to infect humans who do not serve as definitive hosts. The