Fascioliasis: can Cuba conquer this emerging parasitosis?

Review

Fascioliasis: can Cuba conquer this emerging parasitosis? La´zara Rojas1, Antonio Vazquez1, Ingrid Domenech1 and Lucy J. Robertson2 1 Instituto de Medicina Tropical Pedro Kourı´, Autopista Novia del Mediodia km 61/2, Apartado Postal 601, Marianao 13, Ciudad de La Habana, Cuba 2 Parasitology Laboratory, Department of Food Safety and Infection Biology, Norwegian School of Veterinary Science, 0033 Oslo, Norway

Fascioliasis, an emerging parasitic infection, impacts significantly on both veterinary and human health worldwide. Endemic foci are not limited only to areas of extensive livestock farming, but owing to the parasite’s abilities to colonise new intermediate hosts and adapt to new environments, also occur in other places, including Cuba. In Cuba, despite a high prevalence of fascioliasis in livestock, and the widespread occurrence of two potential intermediate hosts, human infection has decreased steadily over the past 10 years. In other parts of the world, human fascioliasis is apparently becoming more frequent. Problems in counteracting the spread of fascioliasis, and approaches used in Cuba to limit zoonotic transmission are discussed, with emphasis on diagnostic and treatment problems, malacological initiatives, and the importance of an integrated control programme. Such programmes may be of benefit in other countries where the prevalence of human fascioliasis is increasing, and lessons may perhaps be learned from the Cuban approach. A neglected tropical disease Fasciola hepatica (Box 1) is an often-neglected parasitic trematode worm [1] infecting almost 17 million people worldwide [2]. In Latin America, fascioliasis (the human disease caused by infection with the worms) is highly prevalent, with various hyperendemic foci (prevalence >10%), and recent observations indicate that it is expanding steadily [3]. Nevertheless, because data are often published only in local journals, or not at all, and frequently not in English, many people are unaware of the extent of the problem. Fascioliasis is described as an emerging infection, as well as a neglected tropical disease (NTD). Because of its association with livestock, fascioliasis is often considered only in relation to intensive or large cattle- or sheep-farming areas. However, endemic foci also occur elsewhere, including Cuba, partly because of the ability of this parasite to colonise new species of intermediate hosts and adapt to new environments. The excellence of the Cuban health services is acknowledged worldwide regarding elimination or control of parasitic diseases [4]. Here, we discuss the basis and opportunities for conquering this widespread and expanding emerging infection in Cuba, providing a background of fascioliasis in Cuba, including the extent and impact of Corresponding author: Robertson, L.J. ([email protected])

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infection in human and animal populations along with information on the intermediate host and transmission routes (Figure 1). We then consider approaches for control. In Cuba, control is based on a National Control Plan, with scientists, veterinarians, and doctors contributing aspects such as diagnosis and malacological initiatives. Some aspects of this integrated programme might be of relevance to other countries. A brief history of fascioliasis in Cuba and the Caribbean It is assumed that Fasciola hepatica was introduced to the Caribbean in general, and Cuba in particular, by the Spanish conquistadors between 1500 and 1865 and their infected livestock [5–7]. During the first years of colonisation, relatively few cattle were introduced, but, by 1525, Spanish cattle (mostly from Andalucı´a) had spread throughout the Caribbean, and could have been the initial source of F. hepatica in this region [7]. Other hosts brought by Europeans (including sheep, goats, equids, and perhaps pigs) might also have played a role [7]. However, the first autochthonous cases of human fascioliasis were not reported in Cuba until 1931 [8]. By 1944, more than 100 sporadic cases of human fascioliasis had been diagnosed in Cuba, at that time comprising more than 33% of all sporadic cases reported worldwide. In the 1940s, two outbreaks occurred (Table 1), and some authors propose that as many as 10,000 Cubans could have been infected during that period [9]. Thus, Cuba was relatively early in determining that fascioliasis was endemic, with substantial numbers of sporadic infections, and also that the infection had potential for large community-wide outbreaks. Fascioliasis in Cuba and the Caribbean today Although sporadic cases of human fascioliasis continue to be diagnosed in Cuba, particularly in western and central regions, the last outbreak was >10 years ago and the annual incidence is sufficiently low that it is not considered a serious public health problem. The general trend is one of decline. Fewer cases were diagnosed in 2008 than any other year since 1995 (Figure 2), with 90% fewer cases than there were 10 years previously. Four epidemiological patterns for fascioliasis have been described [3,7]: (i) high altitude (associated with transmission via Galba truncatula in Andean countries); (ii) Caribbean insular, as occurs in Cuba, with reduced but repeated outbreaks (Table 1) and other lymnaied species being involved; (iii) an Afro-Mediterranean lowlands pat-

1471-4922/$ – see front matter ß 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.pt.2009.10.005 Available online 10 November 2009

Review

Trends in Parasitology

Box 1. Fascioliasis facts  Fascioliasis is caused by infection with trematodes of the genus Fasciola, of which two zoonotic species are currently recognised, F. hepatica and F. gigantica. Only F. hepatica occurs in Cuba, and F. gigantica is not considered further in this article.  The life cycle of F. hepatica is complex and indirect (see Figure 1); adult flukes (20–30 mm long by 8–12 mm wide) inhabiting the bile duct produce up to 25,000 eggs per day.  Fascioliasis is cosmopolitan; the latitudinal, longitudinal, and altitudinal distributions of fascioliasis are greater than for any other vector-borne disease.  As well as humans, F. hepatica infects a variety of mammalian hosts, and is particularly important as a ruminant disease of goats, sheep, and cattle.  When the excysted juvenile flukes penetrate the intestinal wall, the parenchymal or migratory phase of the infection begins, and the juvenile flukes migrate through the abdominal cavity and penetrate the liver or other organs.  The flukes cause mechanical damage to the organs they penetrate, particularly hepatic tissue, and inflammation, and localised or generalised reactions, result.  Although the flukes’ predilection is the liver, ectopic infections can occur. Ectopic fascioliasis most commonly occurs in the subcutaneous tissues and lymph nodes, but other sites include the brain, eye, lung, and peritoneum.  In the billiary phase of fascioliasis, the flukes enter the bile duct where they mature, feed on blood, and produce eggs. Biliary colic and obstruction of the bile duct may occur.

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tern, typically involving overlap of Fasciola species and different snail hosts, and seasonality; and (iv) a pattern associated with areas surrounding the Caspian, with large epidemics and overlap of snail host species and Fasciola species. A further pattern, associated with F. gigantica in Southeast Asian countries, has recently been proposed [7]. The Caribbean insular pattern is associated with areas of hypoendemicity, defined as prevalences of 10% prevalence of asymptomatic fascioliasis in humans [11]. Although Cuba is in the vanguard

Figure 1. Life cycle of Fasciola hepatica.

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Table 1. Outbreaksa of fascioliasis recorded in Cuba, from 1944 to date Date of outbreak 1944

Outbreak location San Cristobal, Pin˜ar del Rio

Number of persons affected At least 50

1948

Pin˜ar del Rio

Over 600

1983

Villa Clara and Sancti Spı´ritus provinces

Dec. 1993

Villa Clara province

43 cases diagnosed by detection of eggs in faeces; a further 1000 individuals considered to have been affected 12 individuals from 6 different families

1995

La Palma town, Pin˜ar del Rio province

1999

Esmeralda, Camaguey Province

More than 500 individuals with clinical symptoms of whom 82 were diagnosed through direct parasitological techniques and detection of secretion–excretion antigens More than 250 cases diagnosed by coprology and FasciDIG assay

Vehicle of transmission/outbreak epidemiology Transmission vehicle unknown, but ingestion of watercress contaminated with metacercariae suspected. Transmission vehicle unknown, but ingestion of watercress contaminated with metacercariae suspected. Transmission vehicle: watercress and/or lettuce. More females infected than males. Age of infected: 16–60 years. No children infected.

Refs [50]

Transmission vehicle: watercress. More females infected than males. Age of infected: 15-70 years. No children infected. All infected lived in the countryside. Heavy rainfalls resulted in flooding, contaminating lettuce fields situated at the foot of a hill where cattle grazed (and defecated). Transmission vehicle: lettuce. Mostly adults infected, but some children.

[52]

Transmission vehicle: watercress. Mostly adults infected, but some children. All infected were urban dwellers.

[53]

[50]

[51]

[36,53]

a

An outbreak is defined as 2 or more associated cases, or a significant increment in cases in a community above the background levels of sporadic or isolated cases.

among Caribbean nations regarding knowledge of endemic fascioliasis, molecular characterisation of Cuban isolates has not yet been conducted, at either the population or individual level. As the Caribbean insular pattern indicates, although fascioliasis is hypoendemic with regard to human infections, it is highly prevalent in Cuban livestock. As well as being of veterinary and economic importance, the transmission potential to the human population cannot be neglected. The most important livestock populations in Cuba are cattle (4 million), sheep (1.6 million), goats (0.8 million) and buffalo (60,000). In cattle and sheep,

the prevalence of fascioliasis is high [12], and surveillance data compiled by the Institute of Veterinary Medicine, Havana, show that the trend is not decreasing. During 2000–2005, an estimated 40,000–50,000 cases of clinical fascioliasis occurred in cattle annually, but, in 2006 and 2007, this estimate rose to 60,000–70,000. Each veterinary unit in Cuba is required to examine 10% of all livestock animals (cattle, sheep and goats) for fascioliasis, and this proportion increases to 30% when positive cases are detected. Livestock diagnosis is generally done by faeces examination using the Benedek sedimentation method. The number of infection foci identified in cattle annually

Figure 2. Annual diagnosis of human cases of fascioliasis at IPK, Cuba from 1995–2008. The decline in diagnoses in recent years is considered to be due largely to implementation of veterinary public health measures, accessible and compulsory public health education, satisfactory infrastructure regarding water and sanitation, and also destruction of watercress plantations.

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Review between 2000 and 2004 was 1100 in more recent years, with each focus comprising an individual epizootic unit. Although fascioliasis in buffaloes has been shown to be widespread in other parts of the world [13], it is not considered a particular problem in Cuba. No deaths due to fascioliasis were reported in buffalo in 2006 and 2007, although sporadic cases are reported. Although pigs are not generally associated with fascioliasis, a report from Cuba [14] showed that they could be of significance here, particularly in back-yard breeding, with a prevalence at one abattoir reaching 1.8%, and the percentage of liver condemnation due to fascioliasis being as high as that for A. suum larval migration (19.4% of liver condemnations). Sanitary inspections of livers in abattoirs also indicate local and national trends. In 1992, 9.5% of livers from slaughterhouse cattle were affected, increasing to 37.5% by 2000, and disease and death due to hepatic fascioliasis has also risen steadily since the 1990s [15]. In the Villa Clara province in 2001, hepatic fascioliasis was the cause of 78 deaths, and there were 1971 reports of disease in the cattle population (susceptible cow estimate: 33,333). These data, together with the slaughterhouse data, indicate that a substantial proportion of the cattle are asymptomatic carriers, with infection identified only at slaughter. In addition, 139 deaths and 2,533 reports of disease in the ovine population (susceptible sheep estimate: 9,328) were recorded [15]. This high prevalence of fascioliasis in Cuba’s livestock has considerable economic impact [16]. It has been calculated [17] that in a four-year period in a single cattle enterprise 33% of the cattle were affected by fascioliasis, resulting in losses of over half a million US dollars due to liver condemnation, reduction in meat and milk production (for example, an annual loss of over 1.5 million litres of milk was calculated due to reduced production) and purchase of anti-parasitic treatments. As fascioliasis is widespread in Cuban livestock and, apart from specific outbreak situations, the prevalence in the human population is low, zoonotic transmission routes have been largely eliminated, largely through the stringent application of public health measures. This does not solve the veterinary issue, but useful tips (see Box 2) might Box 2. Tips for tackling fascioliasis: the Cuban experience  Human infections: sensitive diagnosis and immediate treatment  Animal infections: sensitive diagnosis of symptomatic infections and appropriate treatment or slaughter; monitoring of asymptomatic infections at slaughter. Maintenance of accurate records. Include not only cattle, sheep, and goats in analyses but also other potential hosts such as buffalo and pigs. Preventative livestock management regimes, including quarantine periods for new livestock.  Identify existing biotopes and treat accordingly, including drainage of swamp land, chemical and/or biological control of vector populations, limiting animal access to high-risk areas.  Improve infrastructure regarding water supply and sanitation.  Assess risks from high risk crops, such as watercress, and, if necessary implement crop destruction.  Accessible public health education, with active community participation.  Pro-actively ensure that farmers and other animal owners are aware of this parasite, how to avoid/eliminate it in their livestock, and that it is a zoonotic infection.

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be gained by countries in which extensive animal fascioliasis has resulted in human infections becoming an important public health burden. Transmission routes to the human population Human cases of fascioliasis in Cuba occur in regions where livestock breeding is most concentrated, and where the intermediate hosts thrive. Both outbreaks and sporadic cases have been associated with consumption of watercress (Nasturtium officinale) and lettuce (Table 1); other vegetables have not been implicated. Although water is often cited as a potential source of human infection, and untreated water in hyperendemic areas may contain floating metacercariae (7 per 500 ml reported from Bolivia [18]), widespread access to improved drinking water sources [4,19] means water is unlikely to be a transmission vehicle in Cuba, with raw green vegetables a more likely infection route. The intermediate host One reason why Fasciola hepatica has spread so successfully is its ability to adapt to authochthonous lymnaeid species in different environments. The likely ancestral snail host of F. hepatica, and, globally, the most important today, is Galba truncatula, but this species is not found in Cuba. Two lymnaeid species do occur in Cuba: Fossaria cubensis, which has been associated with infection transmission, and Pseudosuccinea columella, which, to date, has not been found naturally infected in Cuba, but is known to be susceptible to infection from laboratory studies [20,21] P. columella has been described as an important F. hepatica host in other countries, including Africa [22,23], Australia, and South America [21]. Many Cuban malacological studies have investigated the ecology and population dynamics of both snails. The data produced are important for control strategies (Figure 3). Although both snail species can live in the same habitat, distinct preferences have been noted (Figure 4). Canonical correspondence analysis indicates that most factors affect the species in opposite directions, such that variables such as pH, nitrite and nitrate levels had positive effects on F. cubensis, but negative effects on P. columella. However, the opposite pattern was seen with temperature and total water hardness [24]. P. columella populations vary in susceptibility; some isolates show very high rates of infection in in vitro studies, whereas others are resistant [20]. These resistant populations, distinguishable by morphological, behavioural, and genetic markers [25–27], exhibited lower fecundity and survival compared with non-exposed susceptible snails [20]. Infected susceptible snails, however, showed increased egg laying after onset of cercarial emission and no effect on growth, unlike the increase in size and reduction in fecundity usually observed in most other related snail–trematode systems. Although the physiological basis for these observations needs further study, the increased fecundity could be a compensatory effect related to the reduced survival associated with infection, and means that susceptible snail populations are likely to be maintained even under conditions of infection. Field studies in western Cuba have supported the results of these 29

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Figure 3. Distribution of lymnaeid snail species in Cuba as derived from surveys from mid-1980s onwards, and location of outbreaks of fascioliasis from 1944 to date. NB Although regular surveys of lymnaeid snail species are conducted, logistical difficulties mean that these are probably insufficient and the distribution is under-estimated. A study to correlate human and animal infections with detailed snail surveys is planned.

lab-based studies: although both resistant and susceptible strains of P. columella maintained stable populations over the one-year study period, the abundance of the susceptible strain was higher in the field environment [28]. The fact that this species of snail is an exclusive selfer has also been suggested to contribute to its success in establishing, particularly on tropical islands where predators and competitors can be rare [21]. Combating fascioliasis in Cuba Fascioliasis is a serious threat to human and animal health in Cuba; it exerts a heavy economic toll, and there is a danger that it might impact directly on public health through further outbreaks or increased transmission. Therefore, Cuban public and veterinary health services have directed considerable effort towards control of this trematode. These initiatives can be divided into three

Figure 4. Comparison of the two lymnaeid snail species in Cuba Fossaria cubensis, (a) and Pseudosuccinea columella (b), both of which are susceptible to infection with Fasciola hepatica. Fossaria cubensis has been found naturally infected with F. hepatica in Cuba; has been associated with clinical cases/ outbreaks of fascioliasis in Cuba; is widely distributed in Cuba (found in every province); is amphibian, occurring mostly in muddy areas bordering streams and lakes; apparently prefers more urban localities, and is more abundant in more polluted areas; and thrives best in locations with low densities of Tarebia granifera (thiarid snails). Pseudosuccinea columella has only been infected with F. hepatica in laboratory studies in Cuba, but considered a natural host elsewhere (including Australia, South America, and Africa); to date, there has been no direct association with clinical cases or outbreaks of fascioliasis in Cuba; is limited to west half of Cuba; is not found to the east of Camaguey; is strictly aquatic, found mostly in ponds, small lakes, and flooded agricultural areas; is most abundant in rural ecosystems with lower nitrate and nitrite concentrations; and can apparently readily co-exist with T. granifera, even at high densities.

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categories: (i) diagnosis and treatment; (ii) malacological initiatives; and (iii) development of a National Control Programme. Diagnosis and treatment Diagnostic difficulties continue to hinder advancement in combating fascioliasis globally, largely owing to the nonspecific, elusive clinical picture, prolonged prepatent period, irregular egg excretion, and lack of standardized diagnostic protocols [29]. Classical coprology is simple, rapid and inexpensive, but lacks sensitivity and will not detect infection in incubation or invasive stages, nor ectopic fascioliasis (Box 1). Serological tests, detecting circulating IgG against antigens secreted by migrating immature flukes, have high specificity and sensitivity. However, without re-infection, circulating antigen concentrations decrease during infection (after patency), often to undetectable levels [30]. Various functions for secretory products from both immature and adult flukes have been postulated, including facilitating migration through host tissue, acquisition of nutrients and evasion of host immunity. For screening whole communities at risk, stool antigen detection is more appropriate than blood screening, and various ELISAbased tests have been developed against Fasciola excretory/secretory products that occur in stools. Such an assay was developed in Cuba as early as 1987 [31], refined to a sandwich assay (FasciDIG) by 1994 [32], and shown to be superior to coprological diagnosis during the 1995 fascioliasis outbreak [30]. The FasciDIG assay is now used routinely in Cuba’s national reference laboratory, together with serial coprological analyses. This assay has also been applied to animal fascioliasis, and is suitable for diagnosing F. hepatica infections in sheep [33]. Measurement of stool antigen provided positive results four weeks before egg excretion was detected and continued after circulating antigen levels had been reduced to below detectable levels. The use of faeces rather than serum as the detection matrix has obvious practical and ethical advantages. Further research is currently under way (with Norwegian collaboration) to develop a simple, user-friendly, dip-stick test for use in remote, rural areas where fascioliasis has greatest

Review impact. Recently, other groups have also been active in developing similar coproantigen tests using capture ELISAs based on other monoclonal antibodies (mAbs) [34]. Investigations of fascioliasis treatments were already in progress in Cuba in the 1930s [8]. Globally, development of Triclabendazole (TCZ; marketed as Fasinex1), a benzimidazole with selective action against trematodes, was a significant advance, being active against immature flukes migrating through the liver and adult parasites in the bile ducts. The drug has been used in veterinary medicine since 1983 and in humans since 1989 (marketed as Egaten1). It is considered the drug of choice against fascioliasis [35], with a World Health Organization (WHO) campaign to increase its provision for human treatment worldwide [29]. In one Cuban study, close monitoring of patients was conducted, with hospitalisation for one week after TCZ treatment, followed by home-based monitoring with laboratory analyses regularly for two months post-treatment [36]. Although a high cure rate for TCZ was found, over 60% of patients had adverse treatment reactions. The most important of these was colic-like abdominal pain, reported from 50% of patients and assumed to be associated with parasite expulsion through the bile duct [36]. Although most side effects were mild [36], and are perhaps expected with expulsion of a relatively large parasite (Box 1), the possibility of a milder treatment, or even a vaccination strategy, has not been excluded. Cuban studies found immunization with a monoclonal antibody (mAb) (ES-78), produced in mice immunized with ES antigens from adult worms, conferred passive protection against fascioliasis in mice [37]. As with several parasites, cysteine proteinase activity is the most often described and best characterized activity in Fasciola secretions, and ES-78 has been shown to be reactive against a glycoprotein molecule in the parasite’s digestive system with cysteine proteinase activity, and a b-galactose in its structure, possibly in the form of b-galactose (13) N-acetyl galactosamine [38]. However, the protective effect was not due to inhibition of enzymatic activity, but more probably due to the development of cytotoxic responses, effective against the juvenile stages of the parasite [38]. Nevertheless, further research is necessary to understand the action of ES-78 and increase our knowledge of the role of cysteine proteases, proposed to be key virulence factors [39], in parasite physiology and as possible targets for control. It is anticipated that analysing antibody idiotype expression and using recombinant or synthetically derived peptides will result in further vaccine candidates [38]. More recently, an Australian group has used a multivalent vaccine derived from ES antigens to generate immune responses in the rat fascioliasis model [40]. In Cuba, treatment of livestock against F. hepatica is currently thwarted by the high prevalence of infection, the expense and difficulties in obtaining helminthicides and the knowledge that strains of F. hepatica resistant to TCZ are gradually being identified in livestock populations elsewhere in the world [41]. Strategies to deal with resistance include better use of other fasciolicides and use of combination therapy, as well as development of new drugs [35]. Globally, there has been a recent upsurge of interest

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in natural plant products, previously used in traditional medicine, for deriving new drugs for treatment of fascioliasis [35]. Cuban researchers have already explored such products for combating other parasitic diseases [4], and the time is clearly ripe to explore these approaches further regarding fascioliasis. Malacological initiatives The relatively complicated life cycle of F. hepatica provides opportunities for its interruption, unavailable for parasites with simple, direct life cycles. Thus, interventions can be aimed not only at the adult stage or egg, but also the various environmental stages, those in the intermediate snail host, and the snail host itself. In some endemic countries, malacological control is neither practical nor feasible [42], but, in Cuba, considerable research has been directed towards this approach. As F. cubensis is the most prevalent intermediary host in Cuba, and is the only Cuban lymnaied snail found naturally infected, most research has been targeted towards this species. In addition, this snail’s amphibious nature (Figure 4) means that it is probably more difficult to control than the exclusively aquatic P. columella. Biological control, using the planorbid Helisoma duryi and the thiarid T. granifera [43,44], has had a marked impact on F. cubensis populations in some habitats. Neither of these is a predator of F. cubensis, but they are ecologically more plastic and superior competitors for resources (Figure 5). However, such biological control has seldom been implemented due

Figure 5. Graphical representation of impact of introduction of competitive snail species on the density of F. cubensis populations (data derived from Refs [43,44]).

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Review to the careful and thorough ecological studies that are required, both before and during such initiatives, to ensure that non-target species are not affected. Laboratory-based experiments of chemical control using extracts from endemic plants have also shown some success, with an aqueous extract of Agave legrelliana Jacobi resulting in 90% die-off of snails within 72 hours [45]. However, further experiments must be conducted before such preliminary trials can be transferred to the field. Experiments elsewhere on the effects of Solanum species against G. truncatula [46] have shown promising results, and, since this plant is also found in Cuba, might also be investigated against P. columella and F. cubensis. The disparate ecology of the two lymnaied species in Cuba means that care must be exercised in implementing control strategies: creating conditions that reduce the occurrence of F. cubensis, might lead to colonisation by P. columella, which is known to be highly invasive and can also lay eggs even while shedding cercaria [24]. Further ecological studies on snail populations in different ecosystems are likely to provide important information. Development of a National Control Programme A roadmap for control of the more widespread NTDs of the Caribbean has been described by Hotez and colleagues as requiring an ‘intersectoral’ approach, bridging public health, social services and environmental interventions [47]. This is certainly true for fascioliasis. Despite WHO treatment initiatives supported by relevant pharmaceutical companies, totally integrated fascioliasis control programmes, as Hotez et al. [47] describe, are not widespread globally, although some countries with hyperendemic foci of infection have comprehensive control programmes in place, for example on the Bolivian altiplano (Fascioliasis Control Program in Bolivian Altiplano Communities of South America, http://www.biology.ccsu.edu/doan/FCP/ fcp_program.htm). Furthermore, The WHO foodborne disease initiative [48] might also increase the focus on the value of these programmes for fascioliasis control. In Cuba, the National Fascioliasis Control Programme has been developed by the National Centre of Veterinary Parasitology, and is based mostly on integrated control, focusing on the intermediate host and livestock management. Efforts are made to identify existing biotopes, and then a combination of physical controls (drainage and/or fill-in of swampy areas, or limitation of animal access to high-risk sites), chemical controls (application of broad spectrum molluscicides such as ammonium nitrate or copper sulphate and treatment of affected animals), and biological controls (ducks, snail-eating fish, competitor snails), applied as appropriate. Furthermore, introduction of new cattle into a herd is regulated, with a 40-day quarantine period; emphasis is also placed on the quality of drinking water available for animals [15]. Cuba’s current low endemicity in humans of Fasciola infections is considered to be attributable to implementation of veterinary public health measures, accessible and compulsory public health education, acceptable infrastructure regarding water and sanitation, and also destruction of watercress plantations [29]. The destruction of water32

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cress plantations, which might cause controversy elsewhere, was accepted by the Cuban population as a necessary intervention. This is perhaps a reflection of the fact that the Cuban population is accustomed to the implementation of compulsory public health measures (for example, centrally organised, house-to-house, compulsory mosquito elimination directives to reduce the transmission of dengue), and recognises the impact such measures have had in improving public health. Active community participation in such directives further strengthens this approach. Can Cuba conquer fascioliasis? Cuban public and veterinary health authorities have expended considerable effort towards minimising fascioliasis in the human population, and the reduction in positive diagnoses at the National Reference Laboratory in Havana provides testament to this strategy’s success (Box 2). The widespread availability of treated water, awareness of fascioliasis among medical practitioners, and the low population:physician ratio undoubtedly all contribute to this low endemicity [4] despite high prevalences in livestock, and the extensive occurrence of two potential intermediate snail hosts. Notwithstanding, as long as the F. hepatica life cycle continues in the animal population, the threat to the human population remains and might be elevated under certain conditions, such as when the infrastructure of basic services is compromised, as can occur during severe weather conditions (e.g. during the two severe hurricanes that struck Cuba during 2008) or when other natural or manmade catastrophes arise. In addition, the severity and frequency of infection might be affected by climatic change. Meanwhile, the Cuban veterinary authorities face a difficult task in reducing F. hepatica among the nation’s livestock. The widespread prevalence, the difficulties in obtaining helminthicides, the ubiquity and divergent ecology of F. Cubensis, and the highly invasive nature of P. columella are all facets that exacerbate the problem. Although TCZ-resistant F. hepatica has not yet been detected in Cuba, this is a potential problem that must also be considered, perhaps by further focus on developing alternative or complementary therapies. For successful combat of a zoonotic emerging parasitosis such as fascioliasis, cross-disciplinary interaction is vital. It is essential to couple today’s modern technologies such as molecular diagnostics and immunological techniques, with traditional disciplines, such as medical malacology and infection studies, not only to provide more information and develop effective vaccines, but also to encourage young researchers to enter these fields [49]. These aspects have not been disregarded by the Cuban authorities, with initiatives to encourage such cross-disciplinary activities already in progress. Acknowledgements Many of the human data in this article are derived from internal reports at Instituto de Medicina Tropical Pedro Kourı´, Havana (obtainable via: http:// www.ipk.sld.cu) and the majority of the animal data have been kindly provided from internal reports from Instituto de Medicina Veterinaria, Havana (obtainable via: [email protected]) for which we acknowledge the cooperation of Luis C. Mendez and Rafmary Rodriguez.

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