Zoonotic helminth infections of humans: echinococcosis, cysticercosis and fascioliasis Hector H. Garcia a,b,c, Pedro L. Moro d and Peter M.

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1 Zoonotic helminth infections of humans: echinococcosis, cysticercosis and fascioliasis Hector H. Garcia a,b,c, Pedro L. Moro d and Peter M. Schantz d Purpose of review Tissue parasites of humans are still prevalent in most regions of the world, and are also seen more frequently in developed countries due to increasing travel patterns. In particular, Echinococcus infections still account for hepatic and pulmonary pathology, cysticercosis is a major cause of seizures and epilepsy, and fascioliasis also causes significant liver pathology. This review summarizes current knowledge on clinical and epidemiologic aspects of zoonotic disease caused by tissue helminths. Recent findings Tissue helminth infections remain as a public health concern. Recent research has provided new insights into clinical disease in humans and improved methods for diagnosis, treatment and control, arising mostly from the application of new techniques for immune and molecular diagnosis, availability of data from controlled trials, and development of new vaccines. Specific antiparasitic therapies are now better characterized, and new control tools are available. Summary Recent research has provided new diagnostic technologies applicable to diagnosis, treatment and control, but effective interventions to reduce transmission are rarely applied. Despite some progress in their control, these zoonoses continue to be a major public health problem in many regions both in developing countries and in some more developed ones. Keywords cysticercosis, Echinococcus, Fasciola, helminths, Taenia solium, Zoonoses Curr Opin Infect Dis 20: ß 2007 Lippincott Williams & Wilkins. a Department of Microbiology, School of Sciences, Universidad Peruana Cayetano Heredia, b Cysticercosis Unit, Instituto Nacional de Ciencias Neurologicas, Lima, Peru, c Department of International Health, Johns Hopkins University Bloomberg School of Hygiene and Public Health, Baltimore, Maryland and d Immunization Safety Office, Office of the Chief Science Officer (PLM) and Parasitic Diseases Branch/National Center for Zoonotic, Vectorborne and Enteric Diseases (PMS), Centers for Disease Control and Prevention, Atlanta, Georgia, USA Correspondence to Hector H. Garcia, MD, PhD, Department of Microbiology, School of Sciences, Universidad Peruana Cayetano Heredia. Av. H. Delgado 430, SMP, Lima 31, Lima, Peru Tel: ; fax: ; hgarcia@jhsph.edu Current Opinion in Infectious Diseases 2007, 20: Abbreviations CT computed tomography PAIR puncture, aspiration, injection and re-aspiration ß 2007 Lippincott Williams & Wilkins Introduction The larval stage of two cestodes (Echinococcus spp. and Taenia solium) and one trematode (Fasciola spp.) commonly inhabit the human organs and are a frequent cause of human morbidity and mortality. Unlike taeniasis/ cysticercosis and fascioliasis, which are endemic in rural areas in developing countries, hydatid disease is still prevalent in some regions of industrialized countries. New diagnostic technologies, treatment efficacy data from controlled trials, and new control tools including vaccine candidates are now available. Echinococcosis (E. granulosus/e. multilocularis) Echinococcosis is still a frequent cause of liver and lung disease in many countries. E. granulosus and E. multilocularis present very different clinical manifestations. Biology/life cycle The life cycle of Echinococcus species involve carnivores as final hosts and herbivores as intermediate hosts. Humans are an incidental intermediate host, since further development of these cestodes depends on ingestion of their larvae by a carnivore [1 ]. Epidemiology E. granulosus is prevalent in broad regions of Eurasia, in several South American countries and in Africa [2]. In North America most cases are diagnosed in immigrants from endemic countries. Re-emergence seems to have occurred in Bulgaria where the incidence of cystic echinococcosis in children increased from 0.7 to 5.4/ between the 1970s and the mid-1990s, following the collapse of control efforts [2]. In Wales, the prevalence of infected dogs has more than doubled between 1993 (3.4%) and 2002 (8.1%), following policy changes favoring health education over weekly dosing of dogs with praziquantel [2]. E. multilocularis is endemic in the central part of Europe, parts of the near east, Russia, and the central Asian republics, China, northern Japan and Alaska [2]. 489

2 490 Tropical and travel-associated diseases Recent findings show major endemic areas for both Echinococcus species in China [3,4 ]. Clinical features In humans, hydatid cysts of E. granulosus are slowly enlarging masses comparable to benign neoplasms; most human infections remain asymptomatic. The clinical manifestations of cystic hydatid disease are variable and are determined by the site, size, and condition of the cysts [1 ]. Hydatid cysts in the liver and the lungs together account for 90% of affected localizations. In alveolar hydatid disease, the embryo of E. multilocularis seems to localize invariably in the liver of the intermediate host. The hepatic parenchyma is gradually invaded and replaced by fibrous tissue in which great numbers of vesicles, many microscopic, are embedded. Patients eventually succumb to hepatic failure, invasion of contiguous structures, or, less frequently, metastases to the brain [5]. Diagnosis Clinical findings such as a space-occupying lesion and residence in an endemic region are suggestive of cystic hydatid disease [4 ]. Abdominal ultrasonography is an important aid to the diagnosis of abdominal cysts. Chest roentgenography permits the detection of echinococcal cysts in the lungs. Computed tomography (CT) scanning is very helpful, especially for diagnosis of nontypical lesions. Portable ultrasonography machines have been applied for field surveys with excellent results [4,6]. Serologic tests are useful to confirm presumptive radiologic diagnoses, although some patients with cystic echinococcosis do not develop a detectable immune response [7,8]. Hepatic cysts are more likely to elicit an immune response than pulmonary cysts; it appears, however, that, regardless of location, the sensitivity of serologic tests is inversely related to the degree of sequestration of the echinococcal antigens inside cysts. Alveolar hydatid disease may mimic hepatic carcinoma or cirrhosis in patients of advanced age. Plain roentgenography shows hepatomegaly and characteristic scattered areas of radiolucency outlined by calcified rings 2 4 mm in diameter. The usual CT image of E. multilocularis infection is that of indistinct solid tumors with central necrotic areas and perinecrotic plaque-like calcifications [9 ]. Serologic tests are usually positive at high titers [10]. Treatment Surgical removal of hydatid cysts remains the treatment of choice in many countries and it is the preferred treatment when liver cysts are large (>10 cm in diameter), secondarily infected, or located in certain organs (i.e., brain, lung or kidney). Benzimidazole compounds have been shown to be effective against cystic hydatid disease. Courses of albendazole in a dose of mg/kg body weight per day for 28 days are interspersed with drug-free periods of 2 weeks. Approximately a third of patients treated with benzimidazole drugs become cured (e.g. complete and permanent disappearance of cysts) and even higher proportions (30 50%) demonstrate significant regression of cyst size and alleviation of symptoms [11]. Twenty to 40% of cases, however, do not respond favorably. Because of its high scolicidal activity, albendazole is recommended as a prophylactic agent 1 3 months before surgical intervention [12]. The combination of praziquantel and albendazole has been used successfully in the treatment of hydatid disease [12]. Puncture, aspiration, injection and re-aspiration (PAIR) consists of percutaneous puncture using sonographic guidance, aspiration of substantial amounts of the cyst fluid, and injection of a protoscolicidal agent, usually hypertonic saline for at least 15 min, followed by reaspiration of cyst contents [13]. A metaanalysis comparing the use of PAIR and surgical treatment for liver hydatid cysts found fewer complications and a shorter hospital stay in the PAIR-treated group [14]. Alveolar hydatid disease has a high mortality rate with or without surgery. With metastases to the brain, death occurs within a few months after onset of neurologic disorders. Long-term treatment with mebendazole (50 mg/kg per day) or albendazole (10 15 mg/kg) inhibits growth of larval E. multilocularis, reduces metastasis, and enhances both the quality and length of survival; prolonged therapy may eventually be larvicidal in some patients [15]. Liver transplantation has been employed successfully on otherwise terminal cases [16]. Preliminary in-vitro studies suggest nitazoxanide and albendazole may be parasitocidal against E. multilocularis larvae [17] but further efficacy trials in humans are warranted to assess efficacy. Prevention and control Large-scale programs of control of cystic hydatid disease have had noteworthy success only in Iceland, New Zealand, Australia, Tasmania, and Cyprus, where hydatid disease has been eliminated [18 ]. In these countries, the programs have been based on public education combined with strict regulations directed particularly toward control of dogs. Continental programs, such as those of Argentina, Chile and Uruguay, have not experienced this level of success [19 ]. Promising advances include the development of a recombinant vaccine (EG95) against ovine echinococcosis [20] and a vaccine against the dog tapeworm stage [21 ]. Control of

3 Zoonotic helminth infections of humans Garcia et al. 491 E. multilocularis presents a difficult problem of potentially increasing importance. Taeniasis/cysticercosis (Taenia solium) Taenia solium cysticercosis is the most important cause of acquired epilepsy in developing countries and probably in the world. Biology/life cycle Humans are the only definitive host of Taenia solium and acquire the intestinal tapeworm by ingestion of contaminated pork containing larval cysts (cysticerci). The tapeworm, and thus the tapeworm carrier, are the only source of cysticercosis infection for pigs or for other humans. Pigs (the usual intermediate host) acquire cysticercosis by eating stools contaminated with tapeworm proglottids or infective eggs in places where deficient sanitation exists. Humans get infected by fecal oral contamination from a tapeworm carrier, commonly in the household or other close environment [22]. In highly endemic areas, the prevalence of human taeniasis usually ranges between 1 and 2%, while most of the pigs will show serological evidence of exposure to Taenia solium, and over 20% of them may harbor cysts in their flesh. Infected pigs cluster around tapeworm carriers, with clustering extending somewhat beyond the household limits [23 ]. Alternative dispersion mechanisms, including the role of pigs as mechanical vectors, insects, or other vectors contributing to this widespread range, have been suggested [23 ]. Diagnosis Diagnosis of human tapeworm carriers, extremely important for control purposes, has benefited from the availability (albeit somewhat limited) of coproantigen detection tests [24]. Stage-specific serological assays for tapeworm detection have been developed and should be of use. Their main drawback is the lack of information on antibody longevity, which should affect the predictive value of such assays. Diagnosis of neurocysticercosis is mainly made by neuroimaging. MRI is the most sensitive technique for most types of neurocysticercosis, although it may be of poor use for detection of calcified lesions. CT, more available in endemic regions and less expensive, is a useful alternative, particularly if new generation scanners can be used. Serological assays confirm the diagnosis. The assay of choice is an immunoblot using seven purified glycoprotein antigens. This test has 98% sensitivity and 100% specificity in patients with more than one lesion. Sensitivity in single-lesion cases may drop to 70%. Synthetic or recombinant versions of these antigens should facilitate the development of new versions of the assay, less dependent on biological material [25]. Antigen-detection assays could demonstrate the presence of live parasites. The sensitivity of these assays seems to be low in cases of intraparenchymal neurocysticercosis. They may, however, become an important monitoring tool for patients with extraparenchymal neurocysticercosis [26,27 ]. Clinical manifestations and treatment Controlled field studies have consistently demonstrated the association between neurocysticercosis and epilepsy [28,29 32]. In clinical settings, there is now a consensus that antiparasitic therapy is of benefit in most forms of active neurocysticercosis [33,34]. Some groups have proposed the use of increased doses of albendazole (30 mg/kg/day instead of the current 15 mg/kg/day dose) but more controlled evidence on its safety and efficacy are still awaited. Steroids are key in modulating the inflammation resulting from the death of the cysts following antiparasitic treatment, and apparently have an individual, specific beneficial effect in the management of single intraparenchymal brain enhancing lesions (solitary cysticercal granuloma) [35 ]. Long-term, high-dose steroid therapy may be required in cases of extraparenchymal neurocysticercosis, with potentially serious side effects. Methotrexate has been introduced as a steroidsparing agent in this type of patient [36 ]. A subset of patients still requires surgery, mainly to place cerebrospinal fluid shunt mechanisms or to extirpate intraventricular or giant cysts. Neuroendoscopical removal of cysts or fenestration of the third ventricle appear to be promising, less invasive techniques [37,38 ]. Prevention and control Taeniasis/cysticercosis is considered an eradicable disease. Control efforts are centered on the definition of a sustainable, economic, and efficient strategy to interrupt transmission. Several vaccine candidates are now described, with an Australian vaccine demonstrating almost complete protection [39,40,41,42,43 ]. A wide scale elimination program sponsored by The Bill and Melinda Gates Foundation is ongoing in northern Peru, aiming to eliminate transmission in an area of inhabitants. Fascioliasis (Fasciola hepatica/f. gigantica) Infections with F. hepatica and F. gigantica are a frequent cause of liver disease in endemic areas. Biology/life cycle Fascioliasis, infection with the liver flukes, Fasciola hepatica and F. gigantica, results from ingestion of immature stages (metacercariae) on uncooked aquatic vegetation or free swimming in water worldwide, especially in sheep and cattle-raising areas [44]. When swallowed by susceptible mammals, the infective metacercariae excyst, and the larvae penetrate the intestinal wall into the

4 492 Tropical and travel-associated diseases peritoneum and pass through the liver capsule and tissues to the biliary tract [45 ]. The hermaphroditic adult flukes live in the mammalian hosts common and hepatic bile ducts. Operculate ova are evacuated in the feces. Free swimming larvae (miracidia) emerge from the eggs in fresh water habitats and penetrate or are ingested by lymnaeid snails in which they multiply and are released as free-swimming cercariae which attach and encyst as metacercariae on watercress and other aquatic plants. Adult flukes can live as long as 10 years. Epidemiology F. hepatica infections in livestock have been reported from all continents except Antarctica, with highest rates of infection in temperate zones of Bolivia, Peru, Egypt, Iran, Portugal, and France. F. gigantica has a more restricted geographic distribution limited to tropical environments in parts of Africa, the Middle East and south and eastern Asia [44]. Sporadic cases of infection in humans, usually imported, have been diagnosed in the United States [46]. Most patients report having ingested uncooked aquatic vegetation or pond water. Diagnosis The diagnosis should be considered in the patient who lives or has traveled to endemic areas with a history of ingesting fresh water plants or drinking untreated water and having fever, right-upper quadrant pain or intrahepatic cystic lesions together with absolute peripheral blood eosinophilia [46]. Characteristic lesions on hepatic imaging include hypodense tortuous and branching linear tracks under the capsule corresponding to necrosis, and eosinophilic inflammatory infiltrates along the path of larval migration [47]. Endoscopic retrograde cholangiopancreatography (ERCP) is useful to confirm the location of the trematode in the extrahepatic biliary tract [48,49 ]. Definitive diagnosis is made by demonstrating eggs in samples of stool, bile or duodenal aspirates, specific antibodies in serum or by recovering worms at surgery. Quantitation of eggs per gram of feces may underestimate the fluke burden because of the crowding effect whereby higher worm burdens may result in decreased egg production [50 ]. Stool examinations and serologic tests are less useful during acute infection, however, because symptoms develop 1 2 months before eggs or antibodies are detectable in stool or serum, respectively [50,51 ]. Clinical manifestations and treatment Infection with F. hepatica has two distinct clinical phases corresponding to the migratory stages of its life cycle (acute) and to the presence of the worms in their final habitat in the bile ducts (chronic). Many cases are asymptomatic, but mechanical liver damage results from the migrations of juvenile flukes and possibly chemical factors released by the fluke and may compromise liver function, which is reflected in changes of plasma protein concentration (albumin, globulin) and increased levels of hepatic enzymes in blood [45,50 ]; severity of liver damage is related to fluke burden which may not be reflected in the fecal egg concentration because of the crowding effect [50 ]. Marked eosinophilia is seen in most infected persons, and abdominal pain, intermittent fever, weight loss and urticaria are common. Aberrant migration may produce migratory nodules in the skin, painful inflammation of the intestinal wall, and lesions in the lung, brain, genitourinary tract or elsewhere. Within several weeks to months, the symptoms and signs of the acute phase subside as the worms enter the bile ducts. Chronic fascioliasis is usually subclinical, but some persons have symptoms due to inflammation and intermittent obstruction of bile ducts that resemble biliary colic and cholecystitis, and occasionally there is an ascending cholangitis [49,50 ]. Unlike infections with other flukes, fascioliasis responds poorly to praziquantel. First line treatment is a single oral dose of triclabendazole (10 mg/kg), a well tolerated benzimidazole derivative used in veterinary practice that is highly effective against mature and immature flukes [52,53 ]. (Triclabendazole has not been approved for use in humans in the USA. Upon obtaining permission from the FDA, the drug is available from International Apotheke in Zurich, Switzerland, Tel: Further information can be obtained from the CDC Parasitic Diseases Drug Service, Tel: ) Resistance to triclabendazole is now reportedly common in Ireland, the United Kingdom and Australia [53 ], however, and prompts research for understanding mechanisms of resistance and a search for new fasciolicide compounds [54 56 ]. Treatment with bithionol requires doses and causes frequent side effects. (Bithionol is available under an investigational new drug protocol from the CDC Drug Service, Centers For Disease Control and Prevention, Atlanta, GA 30333, USA; Tel: ; evenings, weekends, or holidays: þ ) Nitazoxanide, a broad spectrum antiparasitic drug given orally to adult patients as one 500 mg tablet every 12 h for 6 7 consecutive days, produced rapid clinical improvement and clearance of infection as determined by hepatic imaging findings and negative stool examination [57]. Clinical trials involving more than 300 patients demonstrated cure rates of 49 87% with few and minor side effects (vomiting and abdominal pain) [57,58]. Prevention and control Avoidance of potentially contaminated aquatic vegetation is the most reliable method of prevention. Metacercariae attached to vegetation retain their viability and infectivity for 2 4 weeks despite dipping

5 Zoonotic helminth infections of humans Garcia et al. 493 in potassium permanganate as a preventive [59 ]. Recent progress has been reported in development of a vaccine for use in sheep [60 ]. Conclusion While there have been significant improvements in most areas of knowledge in these three larval helminth infections, they continue to be a significant cause of human disease in many regions of the world. Improved control interventions are still required. Acknowledgement The findings and conclusions in this review are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. Research grants from the Wellcome Trust, The Bill and Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, and the National Institute of Neurological Diseases and Stroke, NIH, USA, support other research by the authors. The sponsors had no role in the design or performance of this paper. References and recommended reading Papers of particular interest, published within the annual period of review, have been highlighted as: of special interest of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (pp ). 1 Schantz PM. Progress in diagnosis, treatment and elimination of echinococcosis and cysticercosis. Parasitol Int 2006; 55:S7 S13. This provides a good overview of the current state of knowledge. 2 Romig T, Dinkel A, Mackenstedt U. The present situation of echinococcosis in Europe. Parasitol Int 2006; 55:S187 S Yang YR, Craig PS, Ito A, et al. A correlative study of ultrasound with serology in an area in China co-endemic for human alveolar and cystic echinococcosis. Trop Med Int Health 2007; 12: Yang YR, Sun T, Li Z, et al. Community surveys and risk factor analysis of human alveolar and cystic echinococcosis in Ningxia Hui Autonomous Region, China. Bull World Health Organ 2006; 84: China was suspected of being an endemic country for alveolar and cystic echinococcosis. This article describes the alarming situation of these zoonoses in China and provides an excellent example of the application of ultrasonography for the study of the epidemiology of echinococcosis. 5 Yang YR, Cheng L, Yang SK, et al. A hospital-based retrospective survey of human cystic and alveolar echinococcosis in Ningxia Hui Autonomous Region, PR China. Acta Trop 2006; 97: Kilimcioglu AA, Ozkol M, Bayindir P, et al. The value of ultrasonography alone in screening surveys of cystic echinococcosis in children in Turkey. Parasitol Int 2006; 55: Zhang W, McManus DP. Recent advances in the immunology and diagnosis of echinococcosis. FEMS Immunol Med Microbiol 2006; 47: Carmena D, Benito A, Eraso E. Antigens for the immunodiagnosis of Echinococcus granulosus infection: An update. Acta Trop 2006; 98: Bresson-Hadni S, Delabrousse E, Blagosklonov O, et al. Imaging aspects and nonsurgical interventional treatment in human alveolar echinococcosis. Parasitol Int 2006; 55:S267 S272. This article describes the use of imaging techniques for diagnosis of alveolar echinococcosis and discusses certain radiological interventional procedures for its treatment. 10 Carmena D, Benito A, Eraso E. The immunodiagnosis of Echinococcus multilocularis infection. Clin Microbiol Infect 2007; 13: Smego RA Jr, Sebanego P. Treatment options for hepatic cystic echinococcosis. Int J Infect Dis 2005; 9: Moro PL, Schantz PM. Echinococcosis: historical landmarks and progress in research and control. Ann Trop Med Parasitol 2006; 100: Nasseri Moghaddam S, Abrishami A, Malekzadeh R. Percutaneous needle aspiration, injection, and reaspiration with or without benzimidazole coverage for uncomplicated hepatic hydatid cysts. Cochrane Database Syst Rev 2006; 19:CD Smego RA Jr, Bhatti S, Khaliq AA, Beg MA. Percutaneous aspiration-injectionreaspiration-drainage plus albendazole or mebendazole for hepatic cystic echinococcosis: a meta-analysis. Clin Inf Dis 2003; 27: Filippou D, Tselepis D, Filippou G, Papadopoulos V. Advances in liver echinococcosis: diagnosis and treatment. Clin Gastroenterol Hepatol 2007; 5: Koch S, Bresson-Hadni S, Miguet JP, et al. Experience of liver transplantation for incurable alveolar echinococcosis: a 45-case European collaborative report. Transplantation 2003; 75: Reuter S, Manfras B, Merkle M, et al. In vitro activities of itraconazole, methiazole, and nitazoxanide versus Echinococcus multilocularis larvae. Antimicrob Agents Chemother 2006; 50: Craig P, Larrieu F. Control of cystic echinococcosis/hydatidosis: Adv Parasitol 2006; 61: This is an excellent review of current echinococcosis control programs with brief descriptions of what the programs entailed. 19 Moro PL, Schantz PM. Cystic echinococcosis in the Americas. Parasitol Int 2006; 55 (Suppl):S181 S186. There are few published reports on the status of echinococcosis in the American subcontinent and this timely article describes the current situation. 20 Gauci C, Heath D, Chow C, Lightowlers MW. Hydatid disease: vaccinology and development of the EG95 recombinant vaccine. Expert Rev Vaccines 2005; 4: Craig PS, McManus DP, Lightowlers MW, et al. Prevention and control of cystic echinococcosis. Lancet Infect Dis 2007; 7: This is an excellent review of control programs and new potential strategies for the prevention of echinococcosis. 22 Garcia HH, Del Brutto OH. Neurocysticercosis: updated concepts about an old disease. Lancet Neurol 2005; 4: Gonzalez AE, Lopez-Urbina T, Tsang B, et al. Transmission dynamics of Taenia solium and potential for pig-to-pig transmission. Parasitol Int 2006; 55 (Suppl):S131 S135. The authors provide a description of a possible alternative mechanism for transmission dispersion. 24 Allan JC, Craig PS. Coproantigens in taeniasis and echinococcosis. Parasitol Int 2006; 55 (Suppl):S75 S Hancock K, Pattabhi S, Whitfield FW, et al. Characterization and cloning of T24, a Taenia solium antigen diagnostic for cysticercosis. Mol Biochem Parasitol 2006; 147: Zamora H, Castillo Y, Garcia HH, et al. Drop in antigen levels following successful treatment of subarachnoid neurocysticercosis. Am J Trop Med Hyg 2005; 73:S Bobes RJ, Hernandez M, Marquez C, et al. Subarachnoidal and intraventricular human neurocysticercosis: application of an antigen detection assay for the diagnosis and follow-up. Trop Med Int Health 2006; 11: Follow-up of serum antigen levels may help to monitor patients with subarachnoid neurocysticercosis. 28 Rajshekhar V, Raghava MV, Prabhakaran V, et al. Active epilepsy as an index of burden of neurocysticercosis in Vellore district, India. Neurology 2006; 67: Despite the fact that neurocysticercosis is endemic in the Indian subcontinent, population-based studies are scarce. This field study provided evidence on the contribution of neurocysticercosis to seizure disorders in India. 29 Del Brutto OH, Santibanez R, Idrovo L, et al. Epilepsy and neurocysticercosis in Atahualpa: a door-to-door survey in rural coastal Ecuador. Epilepsia 2005; 46: Medina MT, Duron RM, Martinez L, et al. Prevalence, incidence, and etiology of epilepsies in rural Honduras: the Salama Study. Epilepsia 2005; 46: Montano SM, Villaran MV, Ylquimiche L, et al. Neurocysticercosis: association between seizures, serology, and brain CT in rural Peru. Neurology 2005; 65: Preux PM, Druet-Cabanac M. Epidemiology and aetiology of epilepsy in sub- Saharan Africa. Lancet Neurol 2005; 4: Del Brutto OH, Roos KL, Coffey CS, Garcia HH. Meta-analysis: Cysticidal drugs for neurocysticercosis: albendazole and praziquantel. Ann Intern Med 2006; 145: The use and benefits of antiparasitic treatment in NCC has been a motive of controversy. This paper reviewed all 11 controlled studies in the literature and concluded that in most cases antiparasitic treatment is of help. 34 Garcia HH, Pretell EJ, Gilman RH, et al. A trial of antiparasitic treatment to reduce the rate of seizures due to cerebral cysticercosis. N Engl J Med 2004; 350:

6 494 Tropical and travel-associated diseases 35 Garg RK, Potluri N, Kar AM, et al. Short course of prednisolone in patients with solitary cysticercus granuloma: a double blind placebo controlled study. J Infect 2006; 53: Steroid treatment may help to reduce the chances of seizure relapse in SCG. 36 Mitre E, Talaat KR, Sperling MR, Nash TE. Methotrexate as a corticosteroidsparing agent in complicated neurocysticercosis. Clin Infect Dis 2007; 44: This provides an interesting alternative to long-term steroid use. 37 Husain M, Rastogi M, Jha DK, et al. Endoscopic transaqueductal removal of fourth ventricular neurocysticercosis with an angiographic catheter. Neurosurgery 2007; 60: The authors describe minimally invasive endoscopical surgery of neurocysticercosis in the intraveous ventricle. 38 Husain M, Jha DK, Rastogi M, et al. Neuro-endoscopic management of intraventricular neurocysticercosis (NCC). Acta Neurochir (Wien) 2007; 149: Endoscopical surgery may be the treatment of choice for ventricular neurocysticercosis. 39 Gauci CG, Verastegui MR, Gilman RH, Lightowlers MW. Taenia solium and Taenia ovis: stage-specific expression of the vaccine antigen genes, TSOL18, TSOL16, and homologues, in oncospheres. Exp Parasitol 2006; 113: Oncosphere antigens were the base for the develepment of vaccines in cysticercosis. This manuscript describes the identification and characterization of protective antigens. 40 Guo A, Jin Z, Zheng Y, et al. Induction of protection against porcine cysticercosis in growing pigs by DNA vaccination. Vaccine 2007; 25: Gonzalez AE, Gauci CG, Barber D, et al. Vaccination of pigs to control human neurocysticercosis. Am J Trop Med Hyg 2005; 72: Sciutto E, Morales J, Martinez JJ, et al. Further evaluation of the synthetic peptide vaccine S3Pvac against Taenia solium cysticercosis in pigs in an endemic town of Mexico. Parasitology 2007; 134: This presents field testing of a Taenia crassiceps based vaccine candidate. 43 Lightowlers MW. Cestode vaccines: origins, current status and future prospects. Parasitology 2006; 133 (Suppl):S27 S42. This is an overview of vaccines against cestodes. 44 Torgerson P, Claxton J. Epidemiology and control. In: Dalton JP, editor. Fasciolosis. New York: CABI; pp Gajewska A, Smago-Kolzlowska K, Wisniewski M. Pathological changes of liver in infection of Fasciola hepatica. Wiad Parasitol 2006; 133: Experimental infections demonstrate extensive liver damage compromising liver function resulting from migrations of immature flukes and possibly chemical factors released by the fluke. 46 MacLean JD, Graeme-Cook FM. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case A 50-year-old man with eosinophilia and fluctuating hepatic lesions. N Engl J Med 2002; 346: Kabaalioglu A, Cubuk M, Senol U, et al. Fascioliasis: US, CT and MRI findings with new observations. Abdom Imaging 2000; 25: Fullerton JK, Vitale M, Vitale GC. Therapeutic endoscopic retrograde cholangiopancreatography for the treatment of Fasciola hepatica presenting as biliary obstruction. Surg Innov 2006; 13: A case of biliary obstruction due to F. hepatica was diagnosed and treated successfully with endoscopic retrograde cholangiopancreatography. 49 Gulsen MT, Savas MC, Koruk M, et al. Fascioliasis: a report of five cases presenting with common bile duct obstruction. Neth J Med 2006; 64: Five patients with obstructive jaundice were diagnosed and successfully managed with endoscopic retrograde cholangiopancreatography. 50 Valero MA, De Rewnzi M, Panova M, et al. Crowding effect on adult growth, prepatent period and egg shedding of Fasciola hepatica. Parasitol 2006; 133: Higher worm burdens in the chronic stage result in decrease prepatent periods, worm growth and egg production (crowding effect); in these cases measurements of eggs per gram of feces tend to underestimate the fluke burden. 51 Espinoza JR, Maco V, Marcos L, et al. Evaluation of FAS2-ELISA for the serological detection of Fasciola hepatica infection in humans. Am J Trop Med Hyg 2007; Detection of specific antibody (FAS2-ELISA) showed consistently higher seroprevalence in comparison with stool positivity rates, but the comparative indices determined by both methods were consistent for each village. 52 Keiser J, Engels D, Buscher G, Utzinger J. Triclabendazole for the treatment of fascioliasis and paragonimiasis. Exper Opin Investig Drugs 2005; 14: Coles GC. Treatment of fascioliasis in human infections. Trans Roy Soc Trop Med Hyg 2006; 100:2. The author reports widespread resistance of F. hepatica to triclabendazole in Ireland, the UK, The Netherlands and Australia as a result of widespread use of this drug to treat liver fluke in livestock. 54 Mottier L, Fairweather I, Lanusse C. Resistance-induced changes in triclabendazole transport in Fasciola hepatica: ivermectin reversal effect. J Parasitol 2006; 92: In-vitro studies demonstrated that an altered influx/efflux mechanism may account for the development of resistance to triclabendazole in F. hepatica. 55 Keiser J, Utzinger J, Tanner M, et al. The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica. J Antimicrob Chemother 2006; 58: Treatment of experimentally infected rats with a synthetic peroxide resulted in 100% reductions in F. hepatica worm burdens. 56 Keiser J, Shu-Hua X, Tanner M, Utzinger J. Artesunate and artemether are effective fasciolicides in the rat model and in vitro. J Antimicrob Chemother 2006; 57: Artesunate and artemether showed promising fasciolicidal activities with artemether showing better tolerability by the hosts. 57 Kabil SM, El Ashry E, Ashraf NK. An open-label clinical study of nitazoxanide in the treatment of human fascioliasis. Curr Therap Res 2000; 61: Favennec L, Jave Ortiz J, Gargala G, et al. Double-blind, randomized, placebocontrolled study of nitazoxanide in the treatment of fascioliasis in adults and children from northern Peru. Aliment Pharmacol Ther 2003; 17: Ashrafi K, Valero MA, Massoud J, et al. Plant-borne human contamination by fascioliasis. Am J Trop Med Hyg 2006; 75: Infectivity of F. hepatica metacercariae was retained for 2 4 weeks despite dipping of contaminated vegetables with potassium permanganate at doses as high as 1200 mg/l. Authors review literature on similar studies. 60 Lopez-Aban J, Casanueva P, Nogal J, et al. Progress in the development of Fasciola hepatica vaccine using recombinant fatty acid binding protein with the adjuvant adaptation system ADAD. Vet Parasitol 2007; 145: This reports development of a potential vaccine against fascioliasis; vaccinated sheep showed lower fluke recovery and improved postinfection weight gain.