1. Trematodes (Flukes) and Cestodes
Jose A. Serpa, M.D.
Assistant Professor
Baylor College of Medicine

2. References
The Travel and Tropical Medicine Manual by Elaine Jong and Christopher Sandford. Fourth Edition, 2008
Principles and Practices of Infectious Diseases. Mandel, Bennett and Dolin. Sixth Edition, 2005
DPDx. Laboratory Identification of Parasites of Public Health Concern (CDC). Second Edition, 2006.
Special thanks to Dr. A.C. White Jr. for allowing me to use some of his slides

3. Agenda Trematodes (flukes): definition and classification
Schistosomes, liver flukes and lung flukes
Cestodes: Intestinal tapeworms
Cestodes: Tissue (cyst) stage (cysticercosis and ecchinococcosis)

4. Cayetano Heredia National Hospital and Institute of Tropical Medicine Alexander von Humboldt, Lima , Peru

5. 1. Trematodes

6. Trematodes
The flukes, or trematodes, are leaf-shaped parasites with a blind bifurcate intestinal tract
Size varies from 1 mm to more than 10cm
Most are hermaphroditic, except schistosomes

7. Classification Blood flukes (Schistosomes)
Hepatobiliary (Clonorchis sinensis, Opistorchis spp. and Fasciola hepatica)
Lung flukes (Paragonimus)
Intestinal flukes (Metagonymus, Heterophyes, Fasciolopsis)

8. Eggs of trematodes
From DPDx, website for laboratory diagnosis of parasitic diseases of the Division of Parasitic Diseases, National Centers for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, [

9. 2. A. Schistosomiasis

10. Schistosomiasis
Trematode infection caused by “blood flukes” which live in venules of the gastrointestinal and genitourinary tract
There are approximately 200 million persons infected in the world (120 million are symptomatic and die each year)
It affects 74 countries (80% of cases occur in Sub-Saharan Africa)

11. Human Schistosomes and their geographic distribution
S. mansoni: Africa, Brazil, Middle East, Caribean
S. haematobium: Africa, Middle East
S. japonicum: China, Phillipines, SE Asia
S. mekongi: Laos, Cambodia
S. intercalatum: Central Africa (less common)

12. Life cycle
Cercariae penetrate human skin during contact or immersion in fresh water inhabited by infected snails
Cercariae transform into schistosomulae , go into bloodstream and then migrate to liver and lung where they mature (4-6 weeks)
Adult male and female pair and migrate to the Sup Mes vein (S. japonicum and S. mekongi), Inf Mesenteric vein (S. mansoni) or venous plexus sorrounding the bladder (S. hematobium)
Eggs are excreted in feces or urine and deposited in fresh water. They hatch, miracidia emerge and infect snails of certain species. Cercariae emerge from infected snails

13. Clinical syndromes Asymptomatic Schistosome (cercarial) dermatitis
Acute Schistosomiasis
Chronic Schistomiasis

14. Schistosome dermatitis
It is due to skin penetration of cercaria
Pruritic maculopapular rash
It can last from hours (first time exposed) to days (previously sensitized)

15. Acute Schistosomiasis (Katayama fever)
Occurs at the time of initial parasite egg-laying (hypersensitivity to egg- associated Ags) about 2-8 weeks after infection
Consists of fever, rash/urticaria, cough, abdominal pain, diarrhea, hepatosplenomegaly and eosinophilia
Usually in persons from non-endemic areas
More common with S. mansoni and S. haematobium

16. Chronic Schistosomiasis
Intermittent dysentery and bowel obstruction
Hepatosplenic disease
Urinary tract disease
Less common: Lung or CNS disease

17. Hepatosplenic schistosomiasis
Occurs in S. mansoni , S. japonicum and S. mekongi
Pathogenesis: granulomas around embolized eggs that become trapped in small portal veins (liver)
Initial stage: hepatomegaly
Later stages: Periportal fibrosis  blocks portal blood flow which leads to portal hypertension (splenic congestion, ascites and esophageal bleed)
HBV or HCV coinfection worsens prognosis

18. Urinary tract disease Occurs in S. haematobium infections
Passage of eggs through the bladder wall cause hematuria and dysuria (inflammation and ulcerations)
Granulomatous lesions with subsequent fibrosis of the bladder wall cause urinary reflux and obstruction (hydroureter, hydronephrosis, chronic bacteriuria, renal failure and squamous carcinoma of bladder)

19. Lung and CNS schistosomiasis
Eosinophilic pneumonitis results when eggs reaching the general circulation are trapped in the alveolar capillaries
Aberrant migration of adult worms or embolization of eggs to the spinal cord or brain can cause transverse myelitis (S. mansoni or S. haematobium) or seizures (S. japonicum) respectively

20. Keep in mind…
Acute infection of humans with avian species of Schistosomes can result in an allergic skin reaction called swimmer’s itch (can not mature in the human host and die in the skin). NO need of antiparasitic therapy
Pathogenic adult Schistosoma can persist in the human host for decades so infections can present in non endemic areas among immigrants from endemic regions

21. An interesting association
Prolonged and recurrent Salmonella bacteremia and/or bacteriuria has been reported in patients chronically infected with schistosomiasis

22. Diagnosis
Persons with a history of freshwater exposure in endemic areas (even if eosinophilia is absent)
Identification of eggs in stool or urine samples
Identification of eggs in tissues (e.g. rectal or bladder mucosa)
Serologic tests (CDC): FAST-ELISA (99% sensitive) and immunoblot (species-specific)
Imaging studies (US, CT, MRI) as clinically indicated

23. Schistosoma eggs

24. Schistosoma eggs in tissues

25. Treatment Praziquantel is the drug of choice
Dosing: 40mg/kg in 2 divided doses on a single day (S. mansoni and S. haematobium) or 60mg/kg in 3 divided doses 4-6h apart on a single day (S. Japonicum)
Artemisinins (e.g. artemether) has antischistosomal as well as antimalarial activity
Steroids can be used along with praziquantel for Katayama fever or CNS disease

26. Prevention and control of Schistosomiasis
Avoid contact with fresh water in endemic areas
Annual mass drug administration of praziquantel
Environmental measures to control the snails and promote sanitary disposal of human excrement (cost beyond the reach of poor countries)

27. 2. B. Liver flukes

28. Liver flukes They include: Clonorchis sinensis Opisthorchis sp.
Fasciola hepatica

29. Clonorchis and Opisthorchis
Largely found in the Far East, Southeast Asia and Russia
The hermaphroditic adult worms measure 5 to 25mm x 2 to 5mm and inhabit the intrahepatic biliary ducts
Humans become infected by eating raw or inadequately cooked fish

30. Life cycle

31. Clinical syndromes Asymptomatic eosinophilia
RUQ abdominal pain with jaundice
Acute biliary obstruction
Acute pancreatitis
Recurrent pyogenic cholangitis
Cholangiocarcinoma

32. Diagnosis and Treatment
Based on identification of eggs in the stool or adult worms during surgery or ERCP
Imaging studies (US, CT or MRI) can demonstrate biliary dilation
Praziquantel is the drug of choice (75mg/kg in 3 divided doses 4-6h apart).
Surgery or ERCP for acute biliary obstruction

33. Fasciola hepatica
Large liver fluke (adult worm measures 3.0 x 1.5 cm) that lives in the bile ducts of its mammalian hosts (humans, sheep and cattle)
Reported in 61 countries from Europe, North Africa, Asia and South America (Bolivia and Peru)
More than 3 million cases in the world

34. Transmission
Parasite eggs passed in stools hatch into miracidia which infects fresh water snails. Cercaria emerge from snails and attach to aquatic plants (encyst as metacercaria)
Humans ingest contaminated aquatic plants (e.g. water cress)
Metacercaria excyst, penetrate the intestinal wall, enter the peritoneum, and then pass through the liver capsule to the biliary tract

35. Clinical syndromes Acute phase 2. Chronic phase
Associated with parasite migration (duodenum – peritoneal cavity – liver) and burrowing through the liver
Causes fever, abdominal pain, hepatomegaly and eosinophilia
2. Chronic phase
Due to biliary involvement
Intermittent “biliary colic”, cholangitis

36. Diagnosis and management
Serology for acute phase
Demonstration of eggs in stools, bile or duodenal aspirates
Imaging studies (US, CT) show linear hepatic tracts
Treatment is with triclabendazole (10mg/kg once or twice). Also bithionol, nitazoxanide.

37. 2. C. Lung flukes

38. Lung flukes Most important species:
Paragonimus westermani, P. heterotremus, P. skrjabini, P. miyazakii (Asia), P. africanus, P uterobilateralis (Africa), P. mexicana, P ecuadoriensis (South and Central America)
Cases reported from Asia, Africa and Central and South America

39. Life cycle
Adult worms lay eggs that are coughed up in the sputum or swallow and passed in the stools
Eggs hatch in freshwater and develop into miracidia that infects snails (cercaria)
Cercaria infects freshwater crustaceans (metacercaria)
Humans are infected when eating raw or inadequately cooked crabs or crayfish
Metacercaria excyst in the duodenum  peritoneum  diaphragm  pleura  lung

40. Clinical manifestations
Pulmonary paragonimiasis
Extrapulmonary paragonimiasis

41. Pulmonary paragonimiasis
Resembles pulmonary tuberculosis
Initial stages: cough productive of brownish sputum with intermittent hemoptysis
Chronic stages: profuse expectoration, dyspnea, hemoptysis, pleural effusions and pneumothorax
CRX: infiltrates, cavities, cysts, nodules, pleural effusions

42. Extrapulmonary paragonimiasis
Ectopic migration of eggs from the bowel
Most common: CNS, skin, liver, peritoneum
CNS: brain lesions (seizures, headaches, visual disturbances), meningitis
Skin: Migratory lesions (resemble cutaneous larva migrans)

43. Diagnosis and treatment
Identification of eggs in stools or sputum
Gram or AFB stain in sputum may destroy eggs
Serology: Immunoblot from CDC (Sen: 96%, Sp: 100%)
Drug of choice is praziquantel (75mg/kg/day divided in 3 doses for 2 days)

44. Adult flukes

45. 3. A. Cestodes Intestinal tapeworms

46. Tapeworms (adult stage)
Tapeworms are segmented flat worms that have a head or scolex (which attaches to the intestine) and rhomboid-shaped segments termed proglottids
The tapeworms elongates from each scolex by forming proglottids (which contain male and female reproductive organs). Adult tapeworms may reach lengths of 4.5 – 10m

47. Clinically important tapeworms
Common name
Transmission
Taenia solium
Pork tapeworm
Ingesting meat (pork) containing larvae
Taenia saginata
Beef tapeworm
Ingesting meat (beef) containing larvae
Dyphilobotrium sp.
Fish tapeworm
Ingesting fish containing larvae
Hymenolepis sp.
Dwarf tapeworm
Accidental ingestion of fecal material (containing eggs)
Dipyllidium caninum
Dog tapeworm
Accidental ingestion of dog fleas

48. Life cycle: generalities
The proglottids (containing eggs) shed periodically in the feces
Eggs are ingested by an intermediate host - cow, pig, fish. Then the eggs hatch and larvae emerge, penetrate the gut and migrate to the tissues (especially the muscle)
The lifecycle is completed when humans ingest encysted larvae-containing meat

49. Epidemiology
T. solium is prevalent worldwide (60 million) but rare in US except in immigrants from endemic areas of Latin America and Asia
T. saginata is found worldwide (60 million), especially in Africa and Latin America. In the US, it is seen among people who eat raw or undercooked beef (e.g. steak tartare)
D. latum is prevalent worldwide (10 million) particularly among people who ingest raw, pickled, or marinated fish. D. latum in the US has been associated with sushi and sashimi made of raw pacific salmon and some Scandinavian pickled fish dishes (carp, herring, smelt)
H. nana and H. diminuta(dwarf, 2cm long) is prevalent worldwide (30 million) especially in children. Because of person to person spread, nurseries and day-care facilities are sites of transmission

50. Life cycle of Dyphillobotrium

51. Life cycle of Hymenolepis

52. Life cycle of Dipylidium

53. Clinical manifestations
Most infections are asymptomatic or with minor abdominal symptoms.
Patients may complain of passing worms
D. latum can compete for absorption of vitamin B12 causing B12 deficiency.

54. Diagnosis and treatment
Eggs can be identified in the stools, but this may require repeated examinations
The eggs of T. saginata and T. solium indistinguishable
Gravid proglottids or the scolex can be examined to tell the species apart
Treatment is praziquantel

55. Tapeworm eggs

56. Tapeworms

57. 3. B. Cestodes Tissue cysts (larval stage)

58. Cysticercosis
It is a tissue infection (e.g. subcutaneous tissues, brain, eye, muscle, heart, etc) caused by the larval stage of Taenia solium.
Neurocysticercosis = cysticercosis of the nervous system
Cysticercosis is prevalent in Latin America, Sub-Saharan Africa, India, China and Southeast Asia
Serosurveys in endemic areas: up to 10% infection rates. Studies from India, Mexico, Peru, and Ecuador documented that up to half of patients with adult onset seizures had evidence of neurocysticercosis by imaging studies
In the US, NCC is primarily a disease of immigrants (Hispanics from Central America). Local transmission has been documented in the setting of household tapeworm carriers

59. Life cycle of Taenia solium

60. Pathophysiology
There is typically an incubation period of several years before onset of clinical symptoms
This quiescent phase results from the parasite’s ability to evade the host immune system. However as the cysticerci age, they lose this ability which leads to an intense inflammatory reaction (causing seizures)
Over a few months, the inflamed lesion either resolves radiographically or is replaced by a small calcification
Cysticerci in the cerebral ventricles often cause obstructive hydrocephalus as a result of mechanical obstruction

61. Types of neurocysticercosis
Neurocysticercosis can cause a wide spectrum of clinical forms depending on the number of parasites, their location, and the degree of host inflammation
It can be broadly divided into:
Parenchymal: solitary lesion, multiple lesions
Extra-parenchymal disease:
Intraventricular cysts
Subarachnoid cysts
Spinal cord cysts

62. Parenchymal NCC
A solitary degenerating parenchymal lesion is perhaps the most common presentation of neurocysticercosis worldwide
Seizures are the main clinical manifestation of this type of NCC
Other symptoms: headaches, neurologic focal deficits

64. Extra-parenchymal NCC Intraventricular
Intraventricular cysts typically present with increased intracranial pressure from obstructive hydrocephalus
Headache, nausea, papilledema and altered mental status can also be present

66. Extra-parenchymal NCC Subarachnoid
Subarachnoid NCC causes a wide range of symptoms. Cysts in the fissures (especially the Sylvian fissure) can enlarge to several cm and cause mass effect
Basal subarachnoid cysticercosis carries the worst prognosis since numerous cysticerci may fill the basilar cisterns leading to arachnoiditis. This can present as meningitis, stroke or communicating hydrocephalus
Most of these patients frequently have concomitant ventricular and/or parenchymal disease

68. Calcifications: inactive lesions?

69. Diagnosis Imaging studies: MRI and CT
Serology: Enzyme-linked immunoelectrodifusion transfer blot (EITB) More accurate in serum than in CSF. The assay has a nearly 100% specificity and 98% sensitivity for those with multiple cysticerci. (sensitivity is only 70% in patients with a single parenchymal cyst)
Screening for taeniasis in patients or household contacts(?)

70. Diagnostic criteria
Absolute criteria: Histopathology, Parasites seen in eye, MRI with cyst and scolex
Major criteria: CT/MRI consistent with NCC, +EITB, resolution (spontaneous or with ABZ/PZQ), single enhancing lesion <20 mm w/o Symptoms or signs of other disease
Minor criteria: CT compatible, clinical manifestations c/w NCC, cysticercosis outside CNS (e.g. muscle calcifications)
Epidemiologic criteria: Household contact of tapeworm carrier, residence or prolonged travel to endemic area
Definitive diagnosis: one absolute criterion or two major plus one minor and one epidemiologic criterion
Probable diagnosis: one major plus two minor criteria, one major plus one minor plus one epidemiologic criteria, or three minor plus one epidemiologic criteria

71. Treatment
Symptomatic therapy must be the initial goal of management in neurocysticercosis. (anti-epileptic medications, surgical CSF diversion procedures, and corticosteroids respectively)
Antiparasitic medications also play an important although still controversial role in the treatment of NCC
Surgery (VP shunts, open craniotomy and especially endoscopic removal of cysts) also play a role in selected cases

72. Treatment consensus
Viable or degenerating parenchymal cysts: AED, steroids, antiparasitics
Intraventricular cysts: endoscopic removal of cysts or VPS followed by antiparasitics and steroids
Subarachnoid: Steroids, antiparasitics (repeated courses?) +/- VPS
Calcifications: AED (current rec’s against use of antiparasitics)

73. Hydatid cyst
It is an infection of liver and lung due to the encysted larva of the cestode Echinococcus spp.
Two main species:
E. granulosus: Cystic hydatid disease. Endemic in sheep raising areas of the world (e.g South America, Middle East). There are small foci in the US (California, Utah and Alaska)
E. multilocularis: Alveolar hydatid disease. Endemic in Alaska, Central Europe and Northern Japan
Dogs and wild canines are the definitive hosts (adult worms in intestines). Sheep and catle (E. granulosis) or rodents (E. multilocularis) are the intermediate hosts (hydatic disease)

74. Life cycle

75. Clinical manifestations and diagnosis
Hydatid cyst disease (E. granulosus) presents with a slowly expanding mass lesion usually in the liver (60%) or lungs (25%).
The most serious complications result from cyst rupture, which can cause anaphylaxis or numerous daughter lesions.
Alveolar hydatid disease (E. multilocularis) presents with an expanding infiltrative process (90% in the liver).
Diagnosis: Imaging studies (US, CT), serology (ELISA at CDC) is 83% sensitive

77. Treatment
In experienced centers, E. granulosus cysts are now mainly treated by PAIR procedure (percutaneous aspiration, injection of scolidical agents, and reaspirations).
PAIR should be undertaken while on albendazole therapy (spilled cyst fluid can spread infection to other areas such as the peritoneal cavity)
Chemotherapy alone may be attempted with albendazole for small or inoperable lesions
Surgical removal is the treatment of choice for complicated cysts (e.g. communication with the biliary tract) and for E. multilocularis. Consider pre- and post-operative albendazole