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Vicente Y. Belizario, Jr., Francis Isidore G. Totañes

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medical parasitology echinococcus parasite biology medical science

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This document is on medical parasitology, specifically focusing on extraintestinal cestodes and the Echinococcus spp. It details the life cycle, parasite biology, and pathogenesis and clinical manifestations of this parasite.

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220 MedICal parasItology In the phIlIppInes Extraintestinal Cestodes Vicente Y. Belizario, Jr., Francis Isidore G. Totañes Echinococcus spp. H uman echinococcosis is regarded as an emerging/re-emerging zoonotic disease. The disease is caused by the larval stage of Echinococcus spp., which is ac...

220 MedICal parasItology In the phIlIppInes Extraintestinal Cestodes Vicente Y. Belizario, Jr., Francis Isidore G. Totañes Echinococcus spp. H uman echinococcosis is regarded as an emerging/re-emerging zoonotic disease. The disease is caused by the larval stage of Echinococcus spp., which is acquired when the eggs of this parasite are ingested. Echinococcus spp. belong to the Family Taeniidae, Order Cyclophyllidea. There are six recognized Echinococcus species, four of which are of public health importance. E. granulosus and E. multilocularis cause cystic echinococcosis and alveolar echinococcosis, respectively, while E. vogeli and E. oligarthrus both cause polycystic echinococcosis. E. multilocularis, E. vogeli, and E. oligarthrus are less common because their life cycles are sylvatic. Parasite Biology The adult worm inhabits the small intestines of canines. It measures 3 to 6 mm in length and possesses a pyriform scolex, a short neck, and three proglottids: one immature, one mature, and one gravid. The scolex is typically taeniid in that it has four acetabula. It is armed with 30 to 36 hooks. The gravid proglottid is usually the widest and the longest proglottid. The uterus is midline, with lateral evaginations, and is filled with eggs which resemble those of other taeniid worms. Eggs may be released inside or outside the host. The eggs are swallowed by suitable intermediate hosts, such as goats, horses, camels, and sheep. Man may also accidentally ingest the eggs. The eggs hatch in the duodenum and release oncospheres that penetrate the intestinal wall of the intermediate host. The oncospheres then migrate into the mesenteric venules which lead them to various organs and tissues where they eventually lodge and develop into cysts. The larval stage, called hydatid cyst, is formed through central vesiculation. Cysts may grow at rates ranging from 1 to 5 cm in diameter per year. Numerous protoscolices may be found within the cyst. Development is completed when the cysts in tissues are ingested by carnivores or omnivores. Once inside the definitive host, the protoscolices evaginate and attach to the intestinal wall where they develop into adults. They reside in the small bowel of the host where they start to release eggs that are then passed out in the stool (Figure 4.7). The hydatid cysts usually measure 1 to 7 cm in diameter. The cyst has an outer laminated hyaline layer and an inner nucleated germinal layer. Protoscolices may be found in brood capsules, which contain only the germinal layer, and daughter cysts which are replicas of the mother cysts. The brood capsule may rupture and release protoscolices. Protoscolices and brood capsules that lie free in the cyst are referred to as hydatid sand (Plate 4.16). Up to 2 million protoscolices may be found in an average cyst. Pathogenesis and Clinical Manifestations Pathology of human cystic echinococcosis is caused by the developing larval cyst in the tissues of the intermediate host. The most common and most important site of involvement is the liver, which is seen in 70% of the cases, 85% of which is located in the right lobe. The lungs are involved in 20 to 30% of cases, while other organ involvement, such as the brain and the orbit, make up 10% of cases. Cysts are less commonly seen in the spleen, kidneys, heart, bone, and central nervous system. The cysts of E. granulosus are called unilocular hydatid cysts, while those of E. multilocularis are considered alveolar cysts. As the unilocular cyst Chapter 4: Cestode Infections 221 Figure 4.7. Life cycle of Echinococcus spp. (Accessed from www.dpd.cdc.gov/dpdx) Plate 4.16. Hydatid sand (Courtesy of the Department of Parasitology, UP-CPH) develops, inflammatory reactions may occur in surrounding tissues. Recent studies in mice have shown that infection with E. granulosus leads to down-regulation of inflammatory cytokines, resulting in local immunosuppression. This may be the mechanism by which the parasite is able to escape host cell-mediated response. Mass effect brought about by the enlarging cyst results in organ impairment as the neighboring tissues undergo atrophy and tissue necrosis. Although echinococcal infection may be acquired during childhood, infections involving the liver and the lungs are often diagnosed in adults due to the cysts’ slow growing nature. Simple or uncomplicated cysts may not produce any symptoms, and patients may harbor the cysts for years. In some cases, the presence of the cyst is only an incidental finding in routine 222 MedICal parasItology In the phIlIppInes radiographic examination. Once symptoms start to occur, they typically reflect the site of involvement. Hepatic cysts are mostly found in the inferior right lobe, and may present as hepatic enlargement, right epigastric pain or jaundice. Abdominal cysts may cause discomfort when the cysts are large enough. Cysts may rupture from coughing, muscle strain, trauma, aspiration, and operative procedures. When this happens, the protoscolices, brood capsules, and daughter cysts may metastasize and reach other tissues to develop into secondary cysts after 2 to 8 years. Cysts may also become intrathoracic if they are located in the superior lobe of the liver and rupture into the thoracic region. The rupture of a hepatic cyst into the biliary duct produces a characteristic triad of findings: intermittent jaundice, fever, and eosinophilia. Peribronchial cysts may discharge into a bronchus and result in sudden coughing accompanied by allergic symptoms. Sputum may contain frothy blood, mucus, hydatid fluid, and bits of membrane. Involvement of the brain may cause increased intracranial pressure and Jacksonian epilepsy. Renal involvement may cause intermittent pain, hematuria, kidney dysfunction, and hydatid material in the urine. Secondary infection of the cyst may also occur. Bacteria may enter the cyst and lead to pyogenic abscess formation. A patient with this condition usually presents with chills and high fever. Secondary cysts and infected cysts result in higher mortality rates. In cases where primary cysts rupture, serious anaphylaxis may result from a large amount of hydatid material entering the bloodstream. Multiple cysts on different major organs, seen in 20 to 40% of infected individuals, may consequently result in multiorgan failure. Intrabiliary rupture of the cyst is the most common complication, followed by suppuration. Diagnosis Radiographic findings and/or ultrasonography, combined with a history of residence in an endemic area, and close association with dogs are important in the diagnosis of echinococcosis. The World Health Organization (WHO) has developed a standardized classification system for hepatic cysts detected by ultrasonography, as shown in Table 4.1. Positive serologic tests, such as the use of indirect hemagglutination (IHA), indirect fluorescent antibody (IFA) test, and enzyme immunoassays (EIA) are adjunct to radiologic Table 4.1. WHO classification for hepatic echinococcal cysts Classification Description Type CL Unilocular cystic lesion(s) with uniform anechoic content without pathognomonic signs Type CE1 Unilocular cysts with uniform anechoic content and with pathognomonic signs that include visible cyst wall and ‘snow flake sign’ Type CE2 Multivesicular, multiseptated cysts Type CE3 Anechoic content with detachment of laminated membrane from the cyst wall visible as floating membrane or as ‘water-lily sign’ Type CE4 Heterogeneous hypoechoic or hyperechoic degenerative contents, no daughter cysts present Type CE5 Cysts characterized by thick calcified wall which is arch-shaped, producing a cone-shaped shadow, the degree of calcification may vary from partial to complete diagnosis. These tests have sensitivities ranging from 60 to 90% and may be used as screening tests. Although serology may be useful to confirm presumptive diagnoses, one must be wary of false positive findings which may occur if the patient is infected with other helminths, or if he has a chronic immune disease. A negative finding, on the other hand, will also not completely rule out the disease since some cyst carriers have undetectable antibodies. Serology may have a relatively high sensitivity (80-100%) and specificity (88-96%) if cysts are located in the liver, but when cysts are located in other Chapter 4: Cestode Infections organs such as the lungs and the brain, the serodiagnostic reactivity is lowered, decreasing the reliability of this adjunctive diagnostic test. Detection of IgG antibodies to hydatid cyst fluid-derived native or recombinant antigen B subunit, through ELISA or immunoblot, is the current gold standard serology for human cystic echinococcosis. Treatment Surgical resection is still considered the preferred treatment for echinococcosis presenting with a large (>10 cm in diameter) liver cyst, secondary infection, or cysts in extrahepatic sites. Small (<7 mm in diameter), isolated cysts, uncomplicated cysts, and patients with negative serology respond best to chemotherapy with benzimidazole compounds. Treatment with albendazole (10-15 mg/kg/ day) or mebendazole (40-50 mg/kg/day) for a minimum of three months has been demonstrated to be effective. Percutaneous aspiration, injection, re-aspiration (PAIR) technique may be indicated for patients with single or multiple cysts in the liver, abdominal cavity, spleen, kidney, or bones, who cannot undergo surgery. This technique involves: (a) ultrasound-guided percutaneous puncture, (b) aspiration of substantial amounts of cystic fluid, (c) injection of a protoscolicidal agent (e.g., 95% ethanol or hypertonic saline) for at least 15 minutes, and (d) re-aspiration. Treatment with PAIR plus albendazole or mebendazole has been shown to have greater efficacy and lower rates of morbidity, mortality, and disease recurrence. Epidemiology Cystic echinococcosis is the most common presentation of echinococcal infection in humans, accounting for >95% of global cases, with a burden of disease of about one million disability-adjusted life years (DALYs). There are approximately 2 to 3 million cases of human cystic echinococcosis, and 0.3 to 0.5 million cases of human alveolar echinococcosis 223 worldwide. Cystic echinococcosis is most prevalent in countries in the temperate zones, such as southern South America, the Mediterranean, southern and central parts of Russia, Central Asia, China, Australia, and parts of Africa. Reemergence of cases have been reported in Bulgaria, where the incidence of echinococcosis in children increased from 0.7 to 5.4/100,000 between the 1970s and the mid-1990s. Similarly, prevalence of infected canines in Wales doubled between 1993 (3.4%) and 2002 (8.1%). Filipinos who have traveled to or worked in endemic areas may get infected. A 35-year old Filipino overseas contract worker in the Middle East presented with a right hilar mass on routine chest x-ray. Thoracotomy showed a 10 cm by 6 cm cystic mass containing hydatid sand. Another Filipino overseas contract worker from Iraq presented with a growing mass in the hip area. Biopsy results showed presence of hydatid sand. More recently, a Filipino female, with no apparent history of travel to an endemic area, consulted her physician for neurologic symptoms. Histopathologic findings of tissue obtained during neurosurgery also showed the presence of hydatid sand. Prevention and Control Prevention is achieved by reducing the infected populations and by minimizing opportunities for transmission. Regular testing and quarantine, and treatment of dogs with praziquantel in endemic areas are important control strategies that have resulted in the reduction of echinococcosis cases. To minimize transmission, dogs should not be allowed in slaughterhouses, and refuse from these facilities should be sterilized or properly disposed. Health education should include knowledge on the mode of transmission, and should emphasize the danger of intimate contact with dogs. New strategies for the control and prevention of echinococcosis include vaccination of livestock, which has been proven to provide 224 MedICal parasItology In the phIlIppInes >95% protection against E. granulosus, as well as the development of more sensitive diagnostic techniques for definitive and human hosts. References Ahluwalia BK, Khurana AK, Gupta NC, Mehtani VG. Hydatid cyst of the orbit. Philipp J Ophthalmol. 1989;18(4):145–6. Akkiz H, Akinoglu A. Colakoglu S, Demirytirek H, Yagnrur O. Endoscopic management of biliary hydatid disease. Can J Surgery. 1996;39:287–92. Budke CM. Global socioeconomic impact of cystic echinococcosis. Emerg Infect Dis. 2006; 12:296–303. Canete R, Escobedo AA, Almirall P, Gonzalez ME, Brito K, Cimerman S. Mebendazole in parasitic infections other than those caused by soil-transmitted helminths. Trans R Soc Trop Med Hyg. 2009;103:437–42. Center for Disease Control and Prevention— Division of Parasitic Diseases. Echinococcosis [Internet]. 2011 [cited 2012 Mar 3]. Available from http://www.dpd.cdc.gov/ dpdx/html/Echinococcosis.htm Craig PS, McManus DP, Lightowlers MW, Chabalgoity JA, Garcia HH, Gavidia Cm, et al. Prevention and control of cystic echinococcosis. Lancet Infect Dis. 2007;7:385–94. Dalisay JS. Pulmonary echinococcosis (a case report). Chest Dis. 1985;14(4):148–51. Ito A, Wandra T, Sato MO, Mamuti W, Xiao N, Sako Y, et al. Towards the international collaboration for detection, surveillance and control of taeniasis, cysticercosis and echinococcosis in Asia and the Pacific. Southeast Asian J Trop Med Public Health. 2006;37(suppl 3):82–90. Ito A, Sako Y, Ishikawa Y, Nakao M, Nakaya K. Differential serodiagnosis of cystic and alveolar echinococcosis using ntrtive and recombinant antigens in Japan. Southeast Asian J Trop Med Public Health. 2001;32(Suppl2):111–5. Lightowlers MW, Flisser A, Gauci CG, Heath DD, Jensen O, Rolf R. Vaccination against cysticercosis and hydatid disease. Parasitol Today. 2000;16(5):191–5. Mondragon-dela Pena C, Ramos-Solis S, Barbosa-Cisneros O, Rodriguez-Padilla C, Tavizon- Garcia P, Herrera-Esparza R. Echinococcus granulosus down regulates the hepatic expression of inflammatory cytokines IL- 6 and TNF alpha in BALB/c mice. Parasite. 2002;9(4):351–16. Moro PL, Schantz PM. Echinococcosis: historical landmarks and progress in research and control. Ann Trop Med Parasitol. 2006;100:703–14. Moro PL, Schantz PM. Echinococcosis: a review. Int J Infect Dis. 2009;13:125–33. Romig T, Dinkel A, Mackenstedt U. The present situation of echinococcosis in Europe. Parasitol Int. 2006;55:S187–91. Schantz PM, Gottstein B, Ammann R, Lanier A. Hydatid and the Arctic. Parasitol Today. 1991;7:35–6. Wang Y, Bradshaw I, Rogan MT, Craig PS. Rapid dot-ELISA for the detection of specific antigens in the cyst fluid from human cases of cystic echinococcosis. Ann Trop Med Parasitol. 2002;96(7):691–4. World Health Organization. International classification of ultrasound images in cystic echinococcosis for application in clinical and field epidemiological settings. Acta Trop. 2003;85:253–61. Chapter 4: Cestode Infections 225 Spirometra spp. Winifreda U. de Leon S parganosis refers to the larval infection with the plerocercoid larvae, also known as spargana, of pseudophyllidean tapeworms falling under the Genus Spirometra. There are many species of Spirometra, but those commonly involved in human sparganosis are Spirometra mansoni, Spirometra erinacei, and Spirometra ranarum. Adults of these worms are intestinal parasites of cats, dogs, and other carnivores. Parasite Biology The gravid proglottids of Spirometra sp. have a spiral uterus, in contrast to the rosette uterus observed in Diphyllobothrium sp. Spirometra eggs are operculated and immature, similar to those of Diphyllobothrium, although smaller. Spirometra eggs are passed out with the feces of the definitive hosts and become embryonated in water (Figure 4.8). The coracidium, once Figure 4.8. Life cycle of Spirometra spp. (Accessed from www.dpd.cdc.gov/dpdx) 226 MedICal parasItology In the phIlIppInes released, infects Cyclops and develops into the procercoid larva. Once the infected Cyclops are ingested by the secondary intermediate hosts such as frogs, snakes, and chickens, the procercoid larva develops into the plerocercoid larva which is also known as sparganum (pl. spargana). If the infected tissues of the second intermediate host are ingested by the definitive host (cats and dogs), the plerocercoid larva develops into an adult worm. These adults are usually mistaken for adult Diphyllobothrium latum, although Spirometra sp. adults are shorter. Pathogenesis and Clinical Manifestations Humans may be infected through: (a) drinking water containing Cyclops or copepods infected with procercoid larvae; (b) eating infected second intermediate hosts like frogs, toads, or snakes containing the plerocercoid larvae; (c) applying plerocercoid infected flesh of frogs and snakes as poultices on sores on the eye, vagina, and skin resulting in subsequent penetration into cutaneous tissues; and (d) consumption of infected flesh of paratenic hosts like wild pigs. The resulting condition is called sparganosis. The larvae may be found in any part of the body. Most commonly, they are found in and about the eyes, in the subcutaneous and muscular tissues of the thorax, abdomen, thighs, inguinal region, and in the viscera. Patients may complain of painful edema due to migrating larvae, hence, the condition is also known as migrating tumor. Local indurations, periodic giant urticaria, edema, and erythema with chills, fever, and high eosinophilia may be seen in patients. Diagnosis Sparganosis is diagnosed through the recovery of the plerocercoid larvae from infected tissues. The larvae that are opaque and glistening white usually measure about 3.5 cm in length. When the larvae are flattened, a spatulate scolex can be appreciated, together with pseudosegmentation, and a slit like invagination at the anterior end. Species identification, however, can only be done through experimental animal infection. Treatment The main form of treatment is surgical removal of the larvae from the infected tissues. Praziquantel has been recommended, but its efficacy in humans has not been proven. Epidemiology Cases of sparganosis have been reported worldwide: in Africa, India, Holland, Australia, and South America. In Asia, the majority of cases came from Japan, Korea, Thailand, Malaysia, and Indonesia. The first case reported in the Philippines was in 1935, when a sparganum was recovered from the abdominal wall of a seminarian originally from Pulilan, Bulacan. The second case, reported in 1950, was that of a fisherman from Libon, Albay, presenting with a 4 cm lower chest lump. The third case, reported in 1953, was that of a 50-year old nun, also from Pulilan, Bulacan, complaining of an erythematous, slightly painful, pruritic mass in the inner aspect of the thigh. Although two of the cases were from the same place, it was possible that the nun got infected during her stay as a missionary in Mindanao. A fourth case, reported in 1962, was that of a 46-year old female with a slightly painful, subcutaneous nodule at the base of the neck. In the late 1970’s, and the early 1980’s, two more cases of human sparganosis were confirmed at the Department of Parasitology, College of Public Health, University of the Philippines Manila. In all six cases, the spargana were motile upon excision of the mass. With the last two cases, the spargana showed the typical solid body with worm-like appearance. There Chapter 4: Cestode Infections was pseudosegmentation with a slit-like invagination at the head end. None of the patients gave a history of consuming raw frogs, birds, or snakes, nor did they admit having applied the flesh of such animals as a poultice. Presumably, transmission may have occurred through drinking water with Cyclops containing procercoids. To date, there have been other cases of human sparganosis encountered in the Philippines. One interesting case was the involvement of the central nervous system of an adult female Filipino complaining of headache, seizures, confusion, and hemiparesis. On computed tomography scan, an area of low density, distinct from other brain lesions, was detected. Multi-Dot ELISA technique on the serum and the cerebrospinal fluid of the patient was positive for Spirometra antigen, but not for cysticercus or Paragonimus antigens. The positive reaction was confirmed using the MicroPlate ELISA procedure. The infection may have been acquired through drinking of water contaminated with infected Cyclops. Infection can be prevented by drinking boiled or filtered water, by cooking possible intermediate and paratenic hosts thoroughly, and by avoiding the practice of applying the flesh of frogs to inflamed areas. 227 References Ahluwalia BK, Khurana AK, Gupta NC, Mehtani VG. Hydatid cyst of the orbit. Philipp J Ophthalmol. 1989;18(4):145–6. Akkiz H, Akinoglu A, Qolakoglu S, Demirytirek H, Yagnrur O. Endoscopic management of biliary hydatid disease. Can J Sugery. 1996;39:287–92. Beaver PC, Jung RC, Cupp EW. Clinical parasitology. 9th ed. Philadelphia: Lea & Febiger; 1984. Belding DL. Textbook of parasitology. 3rd ed. New York: Appleton-Century Crofts; 1965. Garcia EY. Toxoplasmosis and sparganosis in native Filipinos (clinical reports). J Philipp Med Assoc. 1950;26:227. Garcia OP, Reyes Al. Sparganosis in Filipinos. With a review of reported cases in the Philippines. J Philipp Med Assoc. 1962;38(8):608–11. Hinz E. Hunman helminthiases in the Philippines. Berlin: Springer-Veriag; 1984. Jeong SC, Bae JC, Hwang SH, Kim HC, Lee BC. Cerebral sparganosis with intracerebral hemorrhage: a case report. Neurology. 1998;50(2):502–3. Mastura AB, Ambu S, Hasnah O, Rosli R. Spargana infection of frogs in Malaysia. Southeast Asian J Trop Med Public Health. 1996;27(1):51–2.

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