fascioliasis: can cuba conquer this emerging parasitosis?

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Page 1: Fascioliasis: can Cuba conquer this emerging parasitosis?

Fascioliasis: can Cuba conquer thisemerging parasitosis?Lazara 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, Cuba2 Parasitology Laboratory, Department of Food Safety and Infection Biology, Norwegian School of Veterinary Science,

0033 Oslo, Norway

Review

Fascioliasis, an emerging parasitic infection, impactssignificantly on both veterinary and human healthworldwide. Endemic foci are not limited only to areasof extensive livestock farming, but owing to the para-site’s abilities to colonise new intermediate hosts andadapt to new environments, also occur in other places,including Cuba. In Cuba, despite a high prevalence offascioliasis in livestock, and the widespread occurrenceof two potential intermediate hosts, human infectionhas decreased steadily over the past 10 years. In otherparts of the world, human fascioliasis is apparentlybecoming more frequent. Problems in counteractingthe spread of fascioliasis, and approaches used in Cubato limit zoonotic transmission are discussed, withemphasis on diagnostic and treatment problems, mala-cological initiatives, and the importance of an integratedcontrol programme. Such programmes may be ofbenefit in other countries where the prevalence ofhuman fascioliasis is increasing, and lessons may per-haps be learned from the Cuban approach.

A neglected tropical diseaseFasciola hepatica (Box 1) is an often-neglected parasitictrematode worm [1] infecting almost 17 million peopleworldwide [2]. In Latin America, fascioliasis (the humandisease caused by infection with the worms) is highlyprevalent, with various hyperendemic foci (prevalence>10%), and recent observations indicate that it is expand-ing steadily [3]. Nevertheless, because data are often pub-lished only in local journals, or not at all, and frequentlynot in English, many people are unaware of the extent ofthe problem. Fascioliasis is described as an emerging in-fection, as well as a neglected tropical disease (NTD).Because of its association with livestock, fascioliasis isoften considered only in relation to intensive or largecattle- or sheep-farming areas. However, endemic foci alsooccur elsewhere, including Cuba, partly because of theability of this parasite to colonise new species of intermedi-ate hosts and adapt to new environments.

The excellence of the Cuban health services is acknowl-edged worldwide regarding elimination or control of para-sitic diseases [4]. Here, we discuss the basis andopportunities for conquering this widespread and expand-ing emerging infection in Cuba, providing a background offascioliasis in Cuba, including the extent and impact of

Corresponding author: Robertson, L.J. ([email protected])

26 1471-4922/$ – see front matter � 2009 Elsevier

infection in human and animal populations along withinformation on the intermediate host and transmissionroutes (Figure 1). We then consider approaches for control.In Cuba, control is based on a National Control Plan, withscientists, veterinarians, and doctors contributing aspectssuch as diagnosis and malacological initiatives. Someaspects of this integrated programmemight be of relevanceto other countries.

A brief history of fascioliasis in Cuba and the CaribbeanIt is assumed that Fasciola hepatica was introduced to theCaribbean in general, and Cuba in particular, by theSpanish conquistadors between 1500 and 1865 and theirinfected livestock [5–7]. During the first years of colonisa-tion, relatively few cattle were introduced, but, by 1525,Spanish cattle (mostly from Andalucıa) had spreadthroughout the Caribbean, and could have been the initialsource of F. hepatica in this region [7]. Other hosts broughtby Europeans (including sheep, goats, equids, and perhapspigs) might also have played a role [7]. However, the firstautochthonous cases of human fascioliasis were notreported in Cuba until 1931 [8]. By 1944, more than 100sporadic cases of human fascioliasis had been diagnosed inCuba, at that time comprising more than 33% of all spora-dic cases reported worldwide. In the 1940s, two outbreaksoccurred (Table 1), and some authors propose that as manyas 10,000 Cubans could have been infected during thatperiod [9]. Thus, Cuba was relatively early in determiningthat fascioliasis was endemic, with substantial numbers ofsporadic infections, and also that the infection had poten-tial for large community-wide outbreaks.

Fascioliasis in Cuba and the Caribbean todayAlthough sporadic cases of human fascioliasis continue tobe diagnosed in Cuba, particularly in western and centralregions, the last outbreak was >10 years ago and theannual incidence is sufficiently low that it is not considereda serious public health problem. The general trend is one ofdecline. Fewer cases were diagnosed in 2008 than anyother year since 1995 (Figure 2), with 90% fewer casesthan there were 10 years previously.

Four epidemiological patterns for fascioliasis have beendescribed [3,7]: (i) high altitude (associated with trans-mission via Galba truncatula in Andean countries); (ii)Caribbean insular, as occurs in Cuba, with reduced butrepeated outbreaks (Table 1) and other lymnaied speciesbeing involved; (iii) an Afro-Mediterranean lowlands pat-

Ltd. All rights reserved. doi:10.1016/j.pt.2009.10.005 Available online 10 November 2009

Page 2: Fascioliasis: can Cuba conquer this emerging parasitosis?

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 sub-

cutaneous 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.

Figure 1. Life cycle of

Review Trends in Parasitology Vol.26 No.1

tern, typically involving overlap of Fasciola species anddifferent snail hosts, and seasonality; and (iv) a patternassociated with areas surrounding the Caspian, with largeepidemics and overlap of snail host species and Fasciolaspecies. A further pattern, associated with F. gigantica inSoutheast Asian countries, has recently been proposed [7].

The Caribbean insular pattern is associated with areasof hypoendemicity, defined as prevalences of <1%, arith-metic mean intensities < 50 epg (eggs per gram), high epgonly in sporadic cases, and human participation in trans-mission through egg shedding generally negligible, withsewage disposal facilities available and outdoor defecationuncommon [3].Whether this pattern is to be found on otherCaribbean islands is not known: the information regardinghuman fascioliasis in other Caribbean countries is out-of-date or unavailable, and, at worst, non-existent. Althoughoutbreaks of human fascioliasis from other Caribbeannations are not reported in the literature, it should beexpected, based on other variables such as access toimproved drinking water and the physician:patient ratio[4], that, in Haiti, for example, human fasciolias is likely tobe more prevalent than in Cuba. The available datasuggest this to be so, with up to 23% of cattle in Haitiinfected [10]. A limited survey in one area of Puerto Rico inthe 1980s found a >10% prevalence of asymptomatic fas-cioliasis in humans [11]. Although Cuba is in the vanguard

Fasciola hepatica.

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Page 3: Fascioliasis: can Cuba conquer this emerging parasitosis?

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

Date of outbreak Outbreak location Number of persons affected Vehicle of transmission/outbreak epidemiology Refs

1944 San Cristobal, Pinar

del Rio

At least 50 Transmission vehicle unknown, but ingestion

of watercress contaminated with metacercariae

suspected.

[50]

1948 Pinar del Rio Over 600 Transmission vehicle unknown, but ingestion

of watercress contaminated with metacercariae

suspected.

[50]

1983 Villa Clara and Sancti

Spıritus provinces

43 cases diagnosed by detection

of eggs in faeces; a further 1000

individuals considered to have

been affected

Transmission vehicle: watercress and/or lettuce. [51]

More females infected than males. Age of infected:

16–60 years. No children infected.

Dec. 1993 Villa Clara province 12 individuals from 6 different

families

Transmission vehicle: watercress. [52]

More females infected than males. Age of infected:

15-70 years. No children infected. All infected

lived in the countryside.

1995 La Palma town,

Pinar del Rio province

More than 500 individuals with

clinical symptoms of whom 82

were diagnosed through direct

parasitological techniques and

detection of secretion–excretion

antigens

Heavy rainfalls resulted in flooding, contaminating

lettuce fields situated at the foot of a hill where

cattle grazed (and defecated).

[36,53]

Transmission vehicle: lettuce.

Mostly adults infected, but some children.

1999 Esmeralda, Camaguey

Province

More than 250 cases diagnosed

by coprology and FasciDIG assay

Transmission vehicle: watercress. [53]

Mostly adults infected, but some children.

All infected were urban dwellers.aAn 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.

Review Trends in Parasitology Vol.26 No.1

among Caribbean nations regarding knowledge of endemicfascioliasis, molecular characterisation of Cuban isolateshas not yet been conducted, at either the population orindividual level.

As the Caribbean insular pattern indicates, althoughfascioliasis is hypoendemic with regard to human infec-tions, it is highly prevalent in Cuban livestock. As well asbeing of veterinary and economic importance, the trans-mission potential to the human population cannot beneglected. The most important livestock populations inCuba are cattle (�4 million), sheep (�1.6 million), goats(�0.8 million) and buffalo (�60,000). In cattle and sheep,

Figure 2. Annual diagnosis of human cases of fascioliasis at IPK, Cuba from 1995–20

implementation of veterinary public health measures, accessible and compulsory publ

also destruction of watercress plantations.

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the prevalence of fascioliasis is high [12], and surveillancedata compiled by the Institute of Veterinary Medicine,Havana, show that the trend is not decreasing. During2000–2005, an estimated 40,000–50,000 cases of clinicalfascioliasis occurred in cattle annually, but, in 2006 and2007, this estimate rose to 60,000–70,000. Each veterinaryunit in Cuba is required to examine 10% of all livestockanimals (cattle, sheep and goats) for fascioliasis, and thisproportion increases to 30% when positive cases aredetected. Livestock diagnosis is generally done by faecesexamination using the Benedek sedimentation method.The number of infection foci identified in cattle annually

08. The decline in diagnoses in recent years is considered to be due largely to

ic health education, satisfactory infrastructure regarding water and sanitation, and

Page 4: Fascioliasis: can Cuba conquer this emerging parasitosis?

Review Trends in Parasitology Vol.26 No.1

between 2000 and 2004 was <1000, but has been >1100 inmore recent years, with each focus comprising an individ-ual epizootic unit. Although fascioliasis in buffaloes hasbeen shown to be widespread in other parts of the world[13], it is not considered a particular problem in Cuba. Nodeaths due to fascioliasis were reported in buffalo in 2006and 2007, although sporadic cases are reported. Althoughpigs are not generally associated with fascioliasis, a reportfrom Cuba [14] showed that they could be of significancehere, particularly in back-yard breeding, with a prevalenceat one abattoir reaching 1.8%, and the percentage of livercondemnation due to fascioliasis being as high as that forA. suum larval migration (19.4% of liver condemnations).

Sanitary inspections of livers in abattoirs also indicatelocal and national trends. In 1992, 9.5% of livers fromslaughterhouse cattle were affected, increasing to 37.5%by 2000, and disease and death due to hepatic fascioliasishasalso risensteadily since the1990s [15]. In theVillaClaraprovince in 2001, hepatic fascioliasis was the cause of 78deaths, and there were 1971 reports of disease in the cattlepopulation (susceptible cow estimate: 33,333). These data,together with the slaughterhouse data, indicate that a sub-stantial proportion of the cattle are asymptomatic carriers,with infection identified only at slaughter. In addition, 139deaths 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 livestockhas considerable economic impact [16]. It has been calcu-lated [17] that in a four-year period in a single cattleenterprise 33% of the cattle were affected by fascioliasis,resulting in losses of over half a million US dollars due toliver condemnation, reduction inmeat andmilk production(for example, an annual loss of over 1.5 million litres ofmilk was calculated due to reduced production) and pur-chase of anti-parasitic treatments.

As fascioliasis is widespread in Cuban livestock and,apart from specific outbreak situations, the prevalence inthe human population is low, zoonotic transmission routeshave been largely eliminated, largely through the strin-gent application of public health measures. This does notsolve 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 asympto-

matic 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 drai-

nage 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.

be gained by countries in which extensive animal fascio-liasis has resulted in human infections becoming animportant public health burden.

Transmission routes to the human populationHuman cases of fascioliasis in Cuba occur in regions wherelivestock breeding is most concentrated, and where theintermediate hosts thrive. Both outbreaks and sporadiccases have been associated with consumption of watercress(Nasturtium officinale) and lettuce (Table 1); other veg-etables have not been implicated. Although water is oftencited as a potential source of human infection, anduntreated water in hyperendemic areas may contain float-ingmetacercariae (7 per 500 ml reported fromBolivia [18]),widespread access to improved drinking water sources[4,19] means water is unlikely to be a transmission vehiclein Cuba, with raw green vegetables a more likely infectionroute.

The intermediate hostOne reason why Fasciola hepatica has spread so success-fully is its ability to adapt to authochthonous lymnaeidspecies in different environments. The likely ancestralsnail host of F. hepatica, and, globally, the most importanttoday, is Galba truncatula, but this species is not found inCuba. Two lymnaeid species do occur in Cuba: Fossariacubensis, which has been associated with infection trans-mission, and Pseudosuccinea columella, which, to date, hasnot been found naturally infected in Cuba, but is known tobe susceptible to infection from laboratory studies [20,21]P. columella has been described as an important F. hepa-tica host in other countries, including Africa [22,23],Australia, and South America [21].

Many Cuban malacological studies have investigatedthe ecology and population dynamics of both snails. Thedata produced are important for control strategies(Figure 3). Although both snail species can live in the samehabitat, distinct preferences have been noted (Figure 4).Canonical correspondence analysis indicates that mostfactors affect the species in opposite directions, such thatvariables such as pH, nitrite and nitrate levels had positiveeffects on F. cubensis, but negative effects on P. columella.However, the opposite pattern was seen with temperatureand total water hardness [24].

P. columella populations vary in susceptibility; someisolates show very high rates of infection in in vitro studies,whereas others are resistant [20]. These resistant popu-lations, distinguishable by morphological, behavioural,and genetic markers [25–27], exhibited lower fecundityand survival compared with non-exposed susceptiblesnails [20]. Infected susceptible snails, however, showedincreased egg laying after onset of cercarial emission andno effect on growth, unlike the increase in size andreduction in fecundity usually observed in most otherrelated snail–trematode systems. Although the physiologi-cal basis for these observations needs further study, theincreased fecundity could be a compensatory effect relatedto the reduced survival associated with infection, andmeans that susceptible snail populations are likely to bemaintained even under conditions of infection. Field stu-dies in western Cuba have supported the results of these

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Page 5: Fascioliasis: can Cuba conquer this emerging parasitosis?

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.

Review Trends in Parasitology Vol.26 No.1

lab-based studies: although both resistant and susceptiblestrains of P. columella maintained stable populations overthe one-year study period, the abundance of the susceptiblestrain was higher in the field environment [28]. The factthat this species of snail is an exclusive selfer has also beensuggested to contribute to its success in establishing,particularly on tropical islands where predators and com-petitors can be rare [21].

Combating fascioliasis in CubaFascioliasis is a serious threat to human and animal healthin Cuba; it exerts a heavy economic toll, and there is adanger that it might impact directly on public healththrough further outbreaks or increased transmission.Therefore, Cuban public and veterinary health serviceshave directed considerable effort towards control of thistrematode. 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) malacologicalinitiatives; and (iii) development of a National ControlProgramme.

Diagnosis and treatment

Diagnostic difficulties continue to hinder advancement incombating fascioliasis globally, largely owing to the non-specific, elusive clinical picture, prolonged prepatentperiod, irregular egg excretion, and lack of standardizeddiagnostic protocols [29]. Classical coprology is simple,rapid and inexpensive, but lacks sensitivity and will notdetect infection in incubation or invasive stages, nor ecto-pic fascioliasis (Box 1). Serological tests, detecting circulat-ing IgG against antigens secreted by migrating immatureflukes, have high specificity and sensitivity. However,without re-infection, circulating antigen concentrationsdecrease during infection (after patency), often to undetect-able levels [30].

Various functions for secretory products from bothimmature and adult flukes have been postulated, includingfacilitating migration through host tissue, acquisition ofnutrients and evasion of host immunity. For screeningwhole communities at risk, stool antigen detection is moreappropriate than blood screening, and various ELISA-based tests have been developed against Fasciola excre-tory/secretory products that occur in stools. Such an assaywas developed in Cuba as early as 1987 [31], refined to asandwich assay (FasciDIG) by 1994 [32], and shown to besuperior to coprological diagnosis during the 1995 fascio-liasis outbreak [30]. The FasciDIG assay is now usedroutinely in Cuba’s national reference laboratory, togetherwith serial coprological analyses. This assay has also beenapplied to animal fascioliasis, and is suitable for diagnos-ing F. hepatica infections in sheep [33]. Measurement ofstool antigen provided positive results four weeks beforeegg excretion was detected and continued after circulatingantigen levels had been reduced to below detectable levels.The use of faeces rather than serumas the detectionmatrixhas obvious practical and ethical advantages. Furtherresearch is currently under way (with Norwegian collab-oration) to develop a simple, user-friendly, dip-stick test foruse in remote, rural areas where fascioliasis has greatest

Page 6: Fascioliasis: can Cuba conquer this emerging parasitosis?

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]).

Review Trends in Parasitology Vol.26 No.1

impact. Recently, other groups have also been active indeveloping similar coproantigen tests using capture ELI-SAs based on other monoclonal antibodies (mAbs) [34].

Investigations of fascioliasis treatments were already inprogress in Cuba in the 1930s [8]. Globally, development ofTriclabendazole (TCZ; marketed as Fasinex1), a benzimi-dazole with selective action against trematodes, was asignificant advance, being active against immature flukesmigrating through the liver and adult parasites in the bileducts. The drug has been used in veterinarymedicine since1983 and in humans since 1989 (marketed as Egaten1). Itis considered the drug of choice against fascioliasis [35],with a World Health Organization (WHO) campaign toincrease its provision for human treatment worldwide [29].In one Cuban study, close monitoring of patients wasconducted, with hospitalisation for one week after TCZtreatment, followed by home-based monitoring withlaboratory analyses regularly for two months post-treat-ment [36]. Although a high cure rate for TCZ was found,over 60% of patients had adverse treatment reactions. Themost important of these was colic-like abdominal pain,reported from �50% of patients and assumed to be associ-ated with parasite expulsion through the bile duct [36].Although most side effects were mild [36], and are perhapsexpected with expulsion of a relatively large parasite (Box1), the possibility of a milder treatment, or even a vaccina-tion strategy, has not been excluded.

Cuban studies found immunization with a monoclonalantibody (mAb) (ES-78), produced inmice immunizedwithES antigens from adult worms, conferred passive protec-tion against fascioliasis in mice [37]. As with severalparasites, cysteine proteinase activity is the most oftendescribed and best characterized activity in Fasciolasecretions, and ES-78 has been shown to be reactiveagainst a glycoprotein molecule in the parasite’s digestivesystem with cysteine proteinase activity, and a b-galac-tose in its structure, possibly in the form of b-galactose (1-3) N-acetyl galactosamine [38]. However, the protectiveeffect was not due to inhibition of enzymatic activity, butmore probably due to the development of cytotoxicresponses, effective against the juvenile stages of theparasite [38]. Nevertheless, further research is necessaryto understand the action of ES-78 and increase our knowl-edge of the role of cysteine proteases, proposed to be keyvirulence factors [39], in parasite physiology and aspossible targets for control. It is anticipated that analysingantibody idiotype expression and using recombinant orsynthetically derived peptides will result in furthervaccine candidates [38]. More recently, an Australiangroup has used a multivalent vaccine derived from ESantigens to generate immune responses in the rat fascio-liasis model [40].

In Cuba, treatment of livestock against F. hepatica iscurrently thwarted by the high prevalence of infection, theexpense and difficulties in obtaining helminthicides andthe knowledge that strains of F. hepatica resistant to TCZare gradually being identified in livestock populationselsewhere in the world [41]. Strategies to deal with resist-ance include better use of other fasciolicides and use ofcombination therapy, as well as development of new drugs[35]. Globally, there has been a recent upsurge of interest

in natural plant products, previously used in traditionalmedicine, for deriving new drugs for treatment of fascio-liasis [35]. Cuban researchers have already explored suchproducts for combating other parasitic diseases [4], and thetime is clearly ripe to explore these approaches furtherregarding fascioliasis.

Malacological initiatives

The relatively complicated life cycle of F. hepatica providesopportunities for its interruption, unavailable for parasiteswith simple, direct life cycles. Thus, interventions can beaimed not only at the adult stage or egg, but also thevarious environmental stages, those in the intermediatesnail host, and the snail host itself. In some endemiccountries, malacological control is neither practical norfeasible [42], but, in Cuba, considerable research has beendirected towards this approach. As F. cubensis is the mostprevalent intermediary host in Cuba, and is the onlyCuban lymnaied snail found naturally infected, mostresearch has been targeted towards this species. Inaddition, this snail’s amphibious nature (Figure 4) meansthat it is probably more difficult to control than the exclu-sively aquatic P. columella. Biological control, using theplanorbid Helisoma duryi and the thiarid T. granifera[43,44], has had a marked impact on F. cubensis popu-lations in some habitats. Neither of these is a predator of F.cubensis, but they are ecologically more plastic andsuperior competitors for resources (Figure 5). However,such biological control has seldom been implemented due

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Review Trends in Parasitology Vol.26 No.1

to the careful and thorough ecological studies that arerequired, both before and during such initiatives, to ensurethat non-target species are not affected. Laboratory-basedexperiments of chemical control using extracts from ende-mic plants have also shown some success, with an aqueousextract of Agave legrelliana Jacobi resulting in 90% die-offof snails within 72 hours [45]. However, further exper-iments must be conducted before such preliminary trialscan be transferred to the field. Experiments elsewhere onthe effects of Solanum species against G. truncatula [46]have shown promising results, and, since this plant is alsofound in Cuba, might also be investigated against P.columella and F. cubensis.

The disparate ecology of the two lymnaied species inCuba means that care must be exercised in implementingcontrol strategies: creating conditions that reduce theoccurrence of F. cubensis, might lead to colonisation byP. columella, which is known to be highly invasive andcan also lay eggs even while shedding cercaria [24].Further ecological studies on snail populations in differ-ent ecosystems are likely to provide important infor-mation.

Development of a National Control Programme

A roadmap for control of themore widespreadNTDs of theCaribbean has been described by Hotez and colleagues asrequiring an ‘intersectoral’ approach, bridging publichealth, social services and environmental interventions[47]. This is certainly true for fascioliasis. Despite WHOtreatment initiatives supported by relevant pharmaceu-tical companies, totally integrated fascioliasis control pro-grammes, as Hotez et al. [47] describe, are not widespreadglobally, although some countries with hyperendemic fociof infection have comprehensive control programmes inplace, for example on the Bolivian altiplano (FascioliasisControl Program in Bolivian Altiplano Communities ofSouth America, http://www.biology.ccsu.edu/doan/FCP/fcp_program.htm). Furthermore, TheWHO foodborne dis-ease initiative [48] might also increase the focus on thevalue of these programmes for fascioliasis control.

In Cuba, the National Fascioliasis Control Programmehas been developed by the National Centre of VeterinaryParasitology, and is based mostly on integrated control,focusing on the intermediate host and livestock manage-ment. Efforts are made to identify existing biotopes, andthen a combination of physical controls (drainage and/orfill-in of swampy areas, or limitation of animal access tohigh-risk sites), chemical controls (application of broadspectrum molluscicides such as ammonium nitrate or cop-per sulphate and treatment of affected animals), and bio-logical controls (ducks, snail-eating fish, competitor snails),applied as appropriate. Furthermore, introduction of newcattle into a herd is regulated, with a 40-day quarantineperiod; emphasis is also placed on the quality of drinkingwater available for animals [15].

Cuba’s current low endemicity in humans of Fasciolainfections is considered to be attributable to implementa-tion of veterinary public health measures, accessible andcompulsory public health education, acceptable infrastruc-ture regarding water and sanitation, and also destructionof watercress plantations [29]. The destruction of water-

32

cress plantations, which might cause controversy else-where, was accepted by the Cuban population as anecessary intervention. This is perhaps a reflection ofthe fact that the Cuban population is accustomed to theimplementation of compulsory public health measures (forexample, centrally organised, house-to-house, compulsorymosquito elimination directives to reduce the transmissionof dengue), and recognises the impact such measures havehad in improving public health. Active communityparticipation in such directives further strengthens thisapproach.

Can Cuba conquer fascioliasis?Cuban public and veterinary health authorities haveexpended considerable effort towards minimising fascio-liasis in the human population, and the reduction inpositive diagnoses at the National Reference Laboratoryin 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 allcontribute to this low endemicity [4] despite high preva-lences in livestock, and the extensive occurrence of twopotential intermediate snail hosts. Notwithstanding, aslong as the F. hepatica life cycle continues in the animalpopulation, the threat to the human population remainsand might be elevated under certain conditions, such aswhen the infrastructure of basic services is compromised,as can occur during severe weather conditions (e.g. duringthe two severe hurricanes that struck Cuba during 2008) orwhen other natural or manmade catastrophes arise. Inaddition, the severity and frequency of infection might beaffected by climatic change.

Meanwhile, the Cuban veterinary authorities face adifficult task in reducing F. hepatica among the nation’slivestock. The widespread prevalence, the difficulties inobtaining helminthicides, the ubiquity and divergentecology of F. Cubensis, and the highly invasive nature ofP. columella are all facets that exacerbate the problem.Although TCZ-resistant F. hepatica has not yet beendetected in Cuba, this is a potential problem that mustalso be considered, perhaps by further focus on developingalternative or complementary therapies.

For successful combat of a zoonotic emerging parasitosissuch as fascioliasis, cross-disciplinary interaction is vital.It is essential to couple today’s modern technologies suchas molecular diagnostics and immunological techniques,with traditional disciplines, such as medical malacologyand infection studies, not only to provide more informationand develop effective vaccines, but also to encourage youngresearchers to enter these fields [49]. These aspects havenot been disregarded by the Cuban authorities, withinitiatives to encourage such cross-disciplinary activitiesalready in progress.

AcknowledgementsMany of the human data in this article are derived from internal reports atInstituto de Medicina Tropical Pedro Kourı, Havana (obtainable via: http://www.ipk.sld.cu) and the majority of the animal data have been kindlyprovided from internal reports from Instituto de Medicina Veterinaria,Havana (obtainable via: [email protected]) for which we acknowledgethe cooperation of Luis C. Mendez and Rafmary Rodriguez.

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