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Author: Subhash Chandra Parija, MBBS, MD, PhD, FRCPath, Director-Professor of Microbiology, Head of Department of Microbiology, Jawaharlal Institute, Postgraduate Medical Education and Research, India

Subhash Chandra Parija is a member of the following medical societies: Indian Academy of Tropical Parasitology, Indian Association of Biomedical Scientists, Indian Association of Medical Microbiologists, Indian Association of Pathologists and Microbiologists, Indian Medical Association, Indian Society for Parasitology, National Academy of Medical Sciences, India, and Royal College of Pathologists

Coauthor(s): Thomas J Marrie, MD, Chair, Professor, Department of Medicine, Division of Infectious Diseases, University of Alberta College of Medicine; Shekhar Koirala, MD, Vice Chancellor, Department of Medicine, BP Koirala Institute of Health, Dharan, Nepal

Editors: Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Ronald A Greenfield, MD, Professor, Department of Internal Medicine, Section of Infectious Diseases, University of Oklahoma College of Medicine; Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital; Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Author and Editor Disclosure

Synonyms and related keywords: trematode infection, trematodiasis, parasites, parasite infection, parasitemia, flukes, blood fluke, lung fluke, liver fluke, intestinal fluke, Paragonimus westermani, P westermani, Clonorchis sinensis, C sinensis, Fasciola hepatica, F hepatica, Opisthorchis viverrini, O viverrini, Fasciolopsis buski, F buski, Heterophyes heterophyes, H heterophyes, Metagonimus yokogawai, M yokogawai, Schistosoma mekongi, S mekongi, Schistosoma intercalatum, S intercalatum, Fasciola gigantica, F gigantica, Echinostoma ilocanum, E ilocanum, Opisthorchis felineus, O felineus, Schistosoma species, schistosomes, Oriental lung fluke, giant intestinal fluke, schistosomiasis, freshwater snails, watercress, fresh-water snails, fresh water snails, pulmonary paragonimiasis, paragonimiasis, swimmer's itch, swimmer itch, cercarial dermatitis, Katayama syndrome, fascioliasis, clonorchiasis, schistosomal infection, fasciolopsiasis, heterophyiasis, metagonimiasis, pyogenic cholangitis, hemiplegia, cephalgia, paresis,cholangiocarcinoma, bilharzia, fasciolosis



Background

Trematode infections occur worldwide. Trematodes, also called flukes, cause various clinical infections in humans. The parasites are so named because of their conspicuous suckers, the organs of attachment (trematos means "pierced with holes"). All the flukes that cause infections in humans belong to the group of digenetic trematodes. Important features exhibited by adult digenetic trematodes are summarized below (see Features of digenic trematodes).

Depending on the habitat in the infected host, flukes can be classified as blood flukes, liver flukes, lung flukes, or intestinal flukes (see Classification of trematodes according to their habitat). The flukes that cause most human infections are Schistosoma species (blood fluke), Paragonimus westermani (lung fluke), and Clonorchis sinensis (liver fluke). Other less important flukes include the liver flukes Fasciola hepatica and Opisthorchis viverrini and the intestinal flukes Fasciolopsis buski, Heterophyes heterophyes, and Metagonimus yokogawai.

Features of digenic trematodes
  • Digenic trematodes are unsegmented leaf-shaped worms that are flattened dorsoventrally.
  • They bear 2 suckers, one surrounding the mouth (oral sucker) and another on the ventral surface of the body (ventral sucker). These serve as the organs of attachment.
  • The sexes of the parasites are not separate (monecious). An exception is schistosomes, which are diecious (unisexual).
  • The alimentary canal is incomplete, and no anus is present.
  • The excretory system is bilaterally symmetrical. It consists of flame cells and collecting tubes. These flame cells provide the basis for the identification of the species.
  • The reproductive system consists of male and female reproductive organs and is complete in each fluke.
  • The flukes are oviparous. They lay operculated eggs. An exception is schistosome eggs, which are not operculated.
  • All have complicated life cycles, with alternating asexual and sexual developments in different hosts. 
Classification of trematodes according to their habitat
  • Blood flukes - Schistosoma haematobium, Schistosoma mansoni, Schistosoma japonicum, Schistosoma mekongi, and Schistosoma intercalatum
  • Liver flukes - F hepatica, Fasciola gigantica, C sinensis, Opisthorchis felineus, and O viverrini
  • Lung flukes - P westermani
  • Intestinal flukes - F buski, M yokogawai, Echinostoma ilocanum, Watsonius watsoni, H heterophyes, and Gastrodiscoides hominis

Pathophysiology

The life cycle of trematodes is completed in 2 different classes of hosts: definitive (ie, humans, domestic animals, wild animals) and intermediate (ie, freshwater snails). Snails that act as intermediate hosts for trematodes of medical importance are listed in Table 2. The list of these hosts for different trematodes and the source of infections are summarized in Table 3.

Blood Flukes (Schistosoma Species)

Schistosomiasis, or bilharzia, is a tropical parasitic disease caused by blood-dwelling fluke worms of the genus Schistosoma. The main schistosomes that infect human beings include S haematobium (transmitted by Bulinus snails and causing urinary schistosomiasis in Africa and the Arabian peninsula), S mansoni (transmitted by Biomphalaria snails and causing intestinal and hepatic schistosomiasis in Africa, the Arabian peninsula, and South America), and S japonicum (transmitted by the amphibious snail Oncomelania and causing intestinal and hepatosplenic schistosomiasis in China, the Philippines, and Indonesia).

S intercalatum and S mekongi are only of local importance. S japonicum is a zoonotic parasite that infects a wide range of animals, including cattle, dogs, pigs, and rodents. S mansoni also infects rodents and primates, but human beings are the main host. A dozen other schistosome species are animal parasites, some of which occasionally infect humans.

Unlike other trematodes, schistosomes have separate sexes, but males and females are found together. The male is short and stout and holds the relatively long female worm in its gynecophoric canal, a groovelike structure. With S haematobium, both male and female live together in the veins that drain the urinary bladder, pelvis, and ureter, whereas S japonicum and S mansoni live in the inferior and superior mesenteric veins, respectively. Hence, these flukes are known as blood flukes. These species are distinguished by their adult and cercarial forms and by their eggs. S haematobium eggs have a terminal spine, but S mansoni and S japonicum eggs have lateral spines and central spines, respectively.

Humans are infected by free-swimming, fork-tailed cercaria in fresh water by penetration of the skin. The cercaria loses its tail and outer layer of glycocalyces, transforms into a schistosomula (a larval form), and travels through venous circulation to the heart, lungs, and portal circulation. Larvae mature and develop into adult worms in approximately 3 weeks and reach the vessels that drain the urinary bladder (S haematobium) or the mesentery (S japonicum, S mansoni). At these venous sites, they live and lay eggs for the duration of the host’s life.

The eggs penetrate the vascular endothelium, enter the bladder or gut lumen, and are excreted in urine (S haematobium) or stool (S japonicum, S mansoni). If these excreted eggs gain access to fresh water, the miracidium emerges from the egg and swims freely until it finds an appropriate snail. In the snail host, after 2 generations of asexual multiplication (sporocysts), the forked-tailed cercariae emerge in water to infect other susceptible human hosts. A single miracidium can multiply in the snail to produce nearly 100,000 cercariae.

Table 1. Comparative Features of Major Human Schistosoma Species



S haematobium

S mansoni

S japonicum

Adult




Body surface of male

Finely tuberculate
Grossly tuberculate
Nontuberculate (smooth)
Testes

4-6, in a cluster
6-9, in a cluster
7, in a linear series
Position of ovary
Posterior to middle of body

Anterior to middle of body
Posterior to middle of body
Number of eggs in uterus

20-30
1-4
50-300
Egg




Size and shape
110-170 μm long
40-70 μm wide
Terminal spine

114-175 μm long
45-68 μm wide
Lateral spine
70-100 μm long
50-65 μm wide
Central spine
Cercaria




Cephalic glands

2 pairs, oxyphilic
2 pairs, basophilic
4 pairs, oxyphilic


Table 2. Vectors and Geographical Areas Associated With Certain Trematode Types

Vector Geographical Area Type of Trematode
Biomphalaria glabrata BrazilS mansoni
Bulinus globosa NigeriaS haematobium
Bulinus truncate IranS haematobium
Oncomelania hupensis nosophora JapanS japonicum
Thiara granifera ChinaP westermani; M yokogawai
Semisulcospira libertine ChinaP westermani; M yokogawai
Polypylis hemisphaerula ChinaF buski
Parafossarulus manchouricus ChinaC sinensis
Bithynia leachi GermanyO felineus
Pirenella conica EgyptH heterophyes
Lymnaea truncatula EnglandF hepatica

Lung Flukes (Paragonimus Species)

The genus Paragonimus contains more than 30 species that have been reported to cause infections in animals and humans. Among these, approximately 10 species have been reported to cause infection in humans, of which P westermani is the most important. P westermani, also known as the Oriental lung fluke, is the most widespread species in Africa, South America, and parts of Asia.

P westermani is a thick, fleshy, reddish brown, egg-shaped worm (7.5-12 mm in length, 4-6 mm in breadth, and 3.5-5 mm in thickness). It inhabits parenchyma of the lung close to bronchioles in humans, foxes, wolves, and various feline hosts (eg, lions, leopards, tigers, cats).

The infection is typically transmitted via ingestion of metacercariae contained in raw freshwater crabs or crayfish. Additionally, consumption of the raw meat of paratenic hosts (eg, omnivorous mammals) may also contribute to human infection. Freshwater snails and crabs are first and second intermediate hosts of Paragonimus species, respectively. In the duodenum, the cyst wall is dissolved, and the metacercariae are released. The metacercariae migrate by penetrating through the intestinal wall, peritoneal cavity, and finally through the abdominal wall and diaphragm into the lungs. There, the immature worms finally settle close to the bronchi, grow, and develop to become sexually mature hermaphrodite worms.

Adult worms begin to lay the eggs, which are unembryonated and are passed out in the sputum. However, if they are swallowed, they are excreted in the feces. The eggs develop further in the water. In each egg, a ciliated miracidium develops during a period of 2-3 weeks. The miracidium escapes from the egg and penetrates a suitable species of snail (first intermediate host), in which it goes through a generation of sporocysts and 2 generations of rediae to form the cercariae. The cercariae come out of the snail, invade a freshwater crustacean (crayfish or crab), and encyst to form metacercariae. When ingested, these cause the infection, and the cycle is repeated.

Liver Flukes (C sinensis, F hepatica)

C sinensis

C sinensis is a widespread parasite found in Southeast Asia that infects the biliary passage in humans. The fluke is oblong, flat, transparent, and relatively small (10-25 mm long and 3-5 mm wide). It has a pointed anterior and rounded posterior end. Humans are infected by eating raw or partially cooked freshwater fish or dried, salted, or pickled fish infected with the metacercariae. In the duodenum, the cyst is digested and an immature larva is released. The larva enters the biliary duct, where it develops and matures into an adult worm. The adult worm feeds on the mucosal secretions and begins to lay fully embryonated operculated eggs, which are excreted in the feces. Upon reaching fresh water and upon ingestion by a suitable species of operculate snails (first intermediate host), the eggs hatch to produce a miracidium. Inside the snail, the miracidia multiply asexually through a single generation of sporocysts and 2 generations of rediae to fork-tailed cercariae.

The cercariae escape from the snail to the water and penetrate under scales of freshwater cyprinid fish (second intermediate host). In the fish, the cercariae lose their tails and encyst in the scale or muscle of the fish to the metacercariae, which are infectious to humans. When ingested, the infected fish cause infection in humans.

F hepatica

Fascioliasis, a zoonotic disease caused by infection with F hepatica (a digenetic trematode), is a major disease of livestock that is associated with important economic losses due to mortality; liver condemnation; reduced production of meat, milk, and wool; and expenditures for anthelmintics. The disease has a cosmopolitan distribution, with cases reported from Scandinavia to New Zealand and southern Argentina to Mexico.

F hepatica, also known as the sheep liver fluke, is a large liver fluke. This fluke primarily causes zoonotic disease in sheep and other domestic animals. Humans are infected by eating watercress and other aquatic plants contaminated by the metacercariae, which enter the duodenum and excyst. They then penetrate the intestinal wall, peritoneal cavity, and liver capsule (Glisson capsule) to reach the bile duct of the liver, where they develop and mature into adult worms.

The adult worms begin to lay the unembryonated eggs, which are excreted in the stool. They develop further in the fresh water. A miracidium hatches out of the egg and invades the appropriate snail host. Inside the snail host, the larva multiplies asexually through a single generation of sporocysts and 2 generations of rediae to finally develop into cercariae. Upon exiting the snail, the cercariae encyst on aquatic plants to form metacercariae. When humans and sheep eat these plants, they become infected, repeating the life cycle.

Intestinal Flukes (F buski, H heterophyes, M yokogawai)

F buski is the most common intestinal nematode that causes infections in humans. The trematodes H heterophyes and M yokogawai are less-common causes of human infection.

F buski, known as the giant intestinal fluke, is found in the duodenum and jejunum of pigs and humans and is the largest intestinal fluke to parasitize humans. Humans are infected by eating freshwater aquatic plants such as water caltrops, water chestnuts, and water bamboo, which can harbor the metacercariae. In the intestine, the metacercariae excyst, attach to the duodenum or jejunum, develop, and grow into adult worms. They lay unembryonated eggs, which are excreted in the feces.

In water, inside the egg, a ciliated miracidium develops, comes out, and penetrates a suitable snail host. Inside the snail, after several stages of asexual multiplication, large numbers of cercariae are produced. The latter emerge from the snail and encyst on the surface of aquatic plants to metacercariae. Ingestion of these plants causes infection in humans, and the cycle is repeated.

Table 3. List of Definitive and Intermediate Hosts and Sources of Infection of Major Trematodes 

Trematode

Definitive Host

Intermediate Host



1st 2nd

Source of Infection


S haematobium


Humans

Freshwater snails (genus Bulinus)

Absent

Contact with water contaminated by cercariae

S mansoni

Humans, occasionally baboons and rodents

Freshwater snails (genus Biomphalaria)

Absent

Penetration of skin by cercariae

S japonicum

Humans, dogs, pigs, cattle, mice, mustelids, and monkeys

Amphibian snails (Oncomelania species)

Absent

Penetration of skin by cercariae

S mekongi

Humans and dogs

Aquatic snails (Tricula aperta)

Absent
Penetration of skin by cercariae

F hepatica

Sheep, goats, cattle, and other herbivorous animals
Amphibian snails (family Lymnaeidae)
Aquatic vegetations and watercress
Ingestion of aquatic plants and watercress infected with metacercariae

C sinensis

Humans, dogs, pigs, cats, rats, and several species of wild animals
Freshwater snails (family Bulinidae)
Freshwater fish (family Cyprinidae)
Eating raw or partially cooked freshwater fish or dried, salted, or pickled fish infected with encysted metacercariae

O felineus

Humans and other fish-eating mammals
Aquatic snails
Freshwater fish
Eating fish infected with metacercariae

P westermani

Humans, wolves, foxes, tigers, leopards, lions, cats, dogs, and monkeys
Freshwater snails (family Pleuroceridae and Thiaridae)
Freshwater crab or crayfish
Ingestion of freshwater crabs or crayfish infected with metacercariae

F buski

Pigs and humans
Planorbid snails of the genera Segmentina, Hippeutis, and Polypylis
Freshwater plants such as water caltrops, water chestnut, water bamboo, water hyacinth, and lotus
Ingestion of freshwater aquatic plants that harbor metacercariae


Frequency

United States

Infection with blood flukes, lung flukes, liver flukes, and intestinal flukes in the United States is extremely rare. The condition is observed in travelers and emigrants from endemic areas.

International

Blood-fluke infections are a re-emerging parasitic disease. Worldwide, more than 250 million people in 74 countries are infected. Currently, 601 million are at risk for C sinensis infection, 293.8 million for infection with Paragonimus species, 91.1 million for infection with Fasciola species, and 79.8 million for infection with Opisthorchis species.39

The geographic distribution of schistosomiasis depends on the presence of the freshwater snails that act as the intermediate hosts. Human infection is caused by skin penetration by the schistosomal cercariae upon contact with the contaminated water sources. Persons susceptible to infection include farmers working in irrigated fields, anglers working in culture ponds and rivers, and persons who wash utensils or clothes along banks of canals or rivers.

Residents who live near freshwater bodies have a risk of infection that is 2.15 times that of persons who live farther from water. Exponential growth of aqua culture may be the most important risk factor for the emergence of foodborne trematodiasis

Foodborne trematodiasis, which is caused by liver flukes (C sinensis, Fasciola species, Opisthorchis species), lung flukes (Paragonimus species), and intestinal flukes (Echinostoma species, F buski, heterophyids), is an emerging public health problem in Southeast Asia and the West Pacific region. In China, the number of clonorchiasis cases have more than tripled over the past decade; approximately 15 million people were infected with C sinensis in 2004.23 

The different species of Schistosoma have different geographic distributions. Urinary schistosomiasis caused by S haematobium is found in 54 countries in Africa and the eastern Mediterranean; intestinal schistosomiasis caused by S japonicum is limited to 4 countries in the Far East (ie, China, Thailand, Indonesia, Philippines). S mansoni is found in 52 countries in Africa and Latin America. S mekongi is found along the banks of the Mekong River area in Southeast Asia.

Approximately 30 million people are infected by liver flukes, of whom 19 million are infected by C sinensis, 9 million by O viverrini, and 1.2 million by O felineus. Of these, approximately 15 million are in China. Liver fluke infection is endemic in China, Japan, Korea, Taiwan, and Vietnam (C sinensis); Thailand and Laos (O viverrini); and the Russian Federation and Eastern Europe (O felineus). People who habitually eat raw or partially cooked fish or dried, salted, or pickled fish are more susceptible to infection by Clonorchis species. Human fascioliasis occurs worldwide in temperate regions.

F hepatica is found on every continent. Nearly 180 million people are at risk for infection, and an estimated 2.4 million people are infected worldwide. The prevalence is highest in areas of extensive sheep and cattle raising and where dietary practices include the consumption of raw aquatic vegetables. In many locations (eg, Portugal, the Nile delta, northern Iran, parts of China, the Andean highlands of Ecuador, Bolivia, and Peru), high infection rates have made fascioliasis a serious public health concern. Outbreaks of F gigantica infection have been reported from tropical areas of Southeast Asia, Africa, and Hawaii.

Human lung fluke infection, most commonly with P westermani, is most common in China, Korea, Thailand, Philippines, and Laos. Humans are infected by eating raw or partially cooked crab or crayfish or crabs soaked in wine as a food delicacy or by drinking juice from raw crabs or crayfish as a part of a food habit. Endemic foci have also been reported from large areas of Peru and Ecuador. Approximately 22 million people are infected globally, of which approximately 10 million infected people are found in China alone. In several provinces of Thailand, the infection rate was found to be 6.5%.

Nearly 100 million people worldwide are infected with F buski. The infection is found most commonly in China, Taiwan, Thailand, Indonesia, Bangladesh, and India. Human infection occurs after ingestion of various parts (eg, fruits, pods, roots, stems) of infected water chestnut, lotus, and other aquatic plants when they are bitten or peeled off with the teeth. Human infection with H heterophyes has been reported in Egypt's Nile delta.

Mortality/Morbidity

Because of the large numbers of people infected worldwide, trematode infections can cause considerable morbidity. Many of the trematode infections, such as schistosomiasis, clonorchiasis, and pulmonary paragonimiasis, can be fatal if left untreated. Infection with intestinal trematodes is rarely fatal.

Race

No racial predisposition to trematode infections is apparent.

Sex

Most trematode infections have no sexual predisposition.

Age

Most trematode infections affect people of all ages equally. However, with intestinal trematode infections, children are affected more severely, as are children and adolescents with schistosomiasis.



History

  • Schistosomiasis
    • Acute manifestations
      • Cercarial dermatitis, also known as swimmer's itch, is an allergic reaction caused by the penetration of cercariae in persons who have been exposed to cercariae in salt water or fresh water. Cercarial dermatitis manifests as petechial hemorrhages with edema and pruritus, followed by maculopapular rash, which may become vesicular. The process is usually related to avian schistosomal species of the genera Trichobilharzia, Gigantobilharzia, and Orientobilharzia, which do not develop further in humans.
      • Katayama syndrome corresponds to maturation of the fluke and the beginning of oviposition. This syndrome is caused by high worm load and egg antigen stimuli that result from immune complex formation and leads to a serum sickness–like illness. This is the most severe form and is most common in persons with S mansoni and S japonicum infections. Symptoms include high fever, chills, headache, hepatosplenomegaly, lymphadenopathy, eosinophilia, and dysentery. A history of travel in an endemic area provides a clue to the diagnosis.
    • Chronic manifestations
      • Symptoms depend on the Schistosoma species that causes the infection, the duration and severity of the infection, and the immune response of the host to the egg antigens.
      • Terminal hematuria, dysuria, and frequent urination are the main clinical symptoms of urinary schistosomiasis.
      • The earliest bladder sign is pseudotubercle, but, in long-standing infection, radiography reveals nests of calcified ova (sandy patches) surrounded by fibrous tissue in the submucosa.
      • Dysentery, diarrhea, weakness, and abdominal pain are the major symptoms of intestinal schistosomiasis.
      • A reaction to schistosomal eggs in the liver causes a periportal fibrotic reaction termed Symmers clay pipestem fibrosis.
      • Hemoptysis, palpitation, and dyspnea upon exertion are the symptoms of schistosomal cor pulmonale that develops as a complication of hepatic schistosomiasis.
      • Headache, seizures (both generalized and focal), myeloradiculopathy with lower limb and back pain, paresthesia, and urinary bladder dysfunction are the noted symptoms of CNS schistosomiasis due to S japonicum infection.
  • Paragonimiasis
    • Acute manifestations: Acute pulmonary infection is characterized by low-grade fever, cough, night sweats, chest pain, and blood-stained rusty-brown sputum.
    • Chronic manifestations: Lung abscess or pleural effusion7 develops in individuals with chronic infections. Fever, hemoptysis, pleurisy pain, dyspnea, and recurrent attacks of bacterial pneumonia are the common symptoms. The condition mimics pulmonary tuberculosis.
    • Fever, headache, nausea, vomiting, visual disturbances, motor weakness, and localized or generalized paralysis are the symptoms of cerebral paragonimiasis.
  • Liver fluke infections
    • Acute manifestations
      • Fascioliasis is mostly subclinical. Acute manifestations are due to migration of larva through lung parenchyma. Malaise, intermittent fever, night sweats, and pain in the right costal area are early symptoms of acute infection.
      • Clonorchiasis is frequently asymptomatic. Serum sickness–like illness with symptoms of high fever, eosinophilia, and rash occurs in individuals with acute infection.
    • Chronic manifestations
      • Chronic fascioliasis is frequently asymptomatic. In symptomatic patients, irregular fever, anemia, hepatobiliary manifestations (colicky pain, jaundice), and secondary bacterial infections are present.
      • In its end stage, chronic clonorchiasis may be complicated by recurrent pyogenic cholangitis and jaundice associated with cholangiocarcinoma.
  • Intestinal fluke infections
    • Acute manifestations: These infections are frequently asymptomatic. Diarrhea and abdominal pain are common symptoms in individuals with acute infection.
    • Chronic manifestations: Generalized abdominal pain; ascites; and edema of the face, abdomen wall, and lower limbs are the main symptoms.

Physical

  • Schistosomiasis

    • Acute infections: Patients may have hepatosplenomegaly, lymphadenopathy, and rashes.
    • Chronic schistosomiasis: Patients may have anemia, pedal edema, ascites, and abdominal distension with distended abdominal veins. Patients may also have intestinal polyposis and signs of malnutrition.
  • Paragonimiasis: Abdominal mass, pain in the abdomen, and mucosanguineous diarrhea characterize abdominal paragonimiasis.
  • Liver fluke infections: Patients with chronic clonorchiasis may have tender hepatomegaly, progressive ascites, catarrhal cholecystitis, progressive edema, and jaundice.
  • Intestinal fluke infections: Patients with mild infection are usually asymptomatic. Patients with severe infections may have ascites and edema of the face, abdomen wall, and lower limbs.

Causes

See Pathophysiology.



Amebiasis
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis D
Hepatitis E
Hepatitis, Viral
Inflammatory Bowel Disease
Leishmaniasis
Pancreatitis, Acute
Pancreatitis, Chronic
Splenomegaly
Tuberculosis
Typhoid Fever
Urinary Tract Infection, Females
Urinary Tract Infection, Males

Other Problems to be Considered

Intestinal helminthic infections
Neurocysticercosis
Epilepsy
Acute nephritis



Lab Studies

  • Microscopy
    • Diagnosis is made after microscopic demonstration of eggs in the stool (intestinal schistosomiasis; intestinal, liver, and lung fluke infections), sputum (pulmonary paragonimiasis), or urine (genitourinary schistosomiasis).
    • Less frequently, nonoperculate terminal-spined eggs of S haematobium can be demonstrated in the rectal biopsy and aspiration findings obtained with proctoscopy or cystoscopy.
    • The flask-shaped eggs of C sinensis can also be demonstrated in the duodenal contents. Examination of fluid obtained from duodenal intubation is diagnostically more sensitive than examination of 2 stool specimens.
    • Formalin ether and/or ethyl acetate concentration is the most sensitive method for processing stool specimens for egg examination.
    • The Kato-Katz technique is a simple and sensitive quantitation technique used successfully in the field.11 It is a commonly used semiquantitative method for counting eggs in persons with intestinal schistosomiasis and allows the degree of infection and treatment response to be assessed.
    • Schistosomal species can be differentiated based on the morphology of the eggs.
    • Urine, the specimen of choice for diagnosing urinary schistosomiasis, is collected between noon and 2 pm, the period when an increased number of eggs are excreted. The eggs in the urine are concentrated by centrifugation or membrane filtration.
    • The eggs of Fasciola and Fasciolopsis species are morphologically similar and indistinguishable. Similarly, the eggs of Clonorchis, Heterophyes, Metagonimus, and Opisthorchis species are also morphologically similar and indistinguishable.
    • In Fasciola and Paragonimus species infections, the eggs cannot be demonstrated during the migratory phase of infection or in ectopic infections because no eggs are passed in the stool.
  • Coproantigen detection: Detection of antigen in the stool (coproantigen) is a nonmicroscopic method of diagnosis. An enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody to an 89-kd antigen of O viverrini has been used to detect coproantigen in the stool of individuals with Opisthorchis infection. This test has been found to be highly sensitive and specific.
  • Soluble egg antigen (SEA) detection: A dip-stick ELISA can be used to assess urine samples for SEA; this method provides an effective diagnosis of schistosomiasis and correlates well with quantitation egg count.
  • Serology
    • Several serologic tests, which can be used to detect either specific antibodies or antigens in the serum, are used in diagnosing trematode infections.
    • Various antibody-based serologic tests are used in the diagnosis of most trematode infections. These tests are used for diagnosis and for seroepidemiologic studies. Commonly used tests include indirect hemagglutination, indirect immunofluorescence, and ELISA. ELISA is most sensitive and practical.
    • These serologic tests are especially useful in the following situations:
      • Prepatent period and in chronic and ectopic cases of schistosomiasis, in which the eggs are difficult to demonstrate in the stool
      • Acute fascioliasis, because the eggs are not passed in the stool for as many as 4 months of infection
      • Cerebral and abdominal paragonimiasis, because the eggs are not passed in the sputum or stool
    • A major disadvantage of antibody-based serologic tests is the inability to differentiate between recent and past infections because antibodies remain in the serum even after parasitologic cure of the disease. Low sensitivity and cross-reactions between trematodes are other noted disadvantages.
    • Detection of specific antigen in serum and urine is particularly useful during acute and end-stage disease, when excretion of eggs is minimal. Knowing whether infection is recent or old is also useful because, in active or recent infection, the circulating antigen is present in the serum or urine but is absent in patients with older or treated infection.
    • Falcon assay screening test (FAST) ELISA is sensitive (95%) and specific (99%) for diagnosis of urinary schistosomiasis. This test uses S hematobium adult worm microsomal antigen (HAMA) to reveal serum antibodies.
    • In schistosomiasis, antigen titers in serum and urine correlate well with the degree of infection, as demonstrated by the egg counts. ELISA is used for detection of proteoglycan gut-associated antigens such as circulating anodic antigen (CAA) and circulating cathodic antigen (CCA) in the urine and serum. The sensitivities of the urine CCA and serum CAA ELISA are substantially higher than those of a single egg count. The sensitivity of these assays increases with egg output. Both CAA and CCA can also be detected in sera and urine of egg-negative individuals.
    • Immunoblot is a specific and sensitive test to detect schistosomiasis.
    • The circulating antigen has been detected in the sera of patients with C sinensis infection with the ELISA double-sandwich method.
    • A dip-stick ELISA can be used to assess urine samples for SEA; this method provides an effective diagnosis of schistosomiasis and correlates well with quantitation egg count. 
    • Protein banding patterns after isoelectric focusing has been used to differentiate F hepatica from F gigantica.  
    • This is useful for monitoring therapeutic studies. No cross-reaction with heterophyid flukes has been reported.
  • Skin tests
    • Intradermal skin testing has been used for epidemiologic studies but cannot be used to differentiate past from current infection.
    • Skin testing using extracts of adult C sinensis or P westermani antigens has been used in Korea and China as an epidemiologic tool.
  • Molecular methods
    • Molecular methods are still in the experimental stage. A polymerase chain reaction (PCR) using the primer named OV-6F/OV-6R has been developed for the detection of O viverrini in experimentally infected hamsters. The method has been found to be 100% sensitive in hamsters.38
    • Multiplex PCR is now available for identification and differentiation of S haematobium, S japonicum, and S mansoni using clinical specimens.
  • Other parameters
    • A complete blood cell count may reveal eosinophilia in patients with fasciolopsiasis, schistosomiasis, heterophyiasis, metagonimiasis, early stages of paragonimiasis, and acute Clonorchis species infection (disappears in chronic Clonorchis species infection).
    • Anemia may be found in patients with schistosomiasis, fascioliasis, and paragonimiasis.
    • Gross and microscopic hematuria may be found in individuals with schistosomiasis.
    • Neutropenia may be found in patients with fasciolopsiasis.
    • Elevation of cerebrospinal fluid (CSF) pressure and pleocytosis and eosinophilia in the CSF may occur in individuals with cerebral paragonimiasis.

Imaging Studies

  • Radiography
    • Chest radiographs in patients with schistosomiasis may reveal cor pulmonale and pulmonary hypertension, if present.
    • Radiographs of the liver exhibit tractlike small abscesses and subcapsular lesions in patients with fascioliasis.
    • Patchy foci of fibrotic change with a characteristic "ring shadow" (ie, circular or oval thin-walled cyst with a crescent-shaped opacity along one side) is the characteristic finding on chest radiographs in patients with paragonimiasis.
  • Ultrasonography
    • Ultrasonography is useful in evaluating the gall bladder and biliary tract in individuals with fascioliasis. Adult worms may be visible on sonograms or may appear as curvilinear lucent areas in the contrast medium on cholangiograms.
    • This is a sensitive procedure used to demonstrate urinary obstruction and hepatosplenic disease in persons with schistosomiasis.19
    • Portable ultrasonography can be used for determining the extent of pathological changes, particularly in the liver and bladder, and can be used to screen populations at the community level. In addition, it can be used to assess the effects of chemotherapy.
  • CT scan
    • CT scan is useful in the study of CNS manifestations of trematode infections.
    • In persons with cerebral paragonimiasis, long-standing cerebral infection forms and cystlike structures may calcify and may be seen as clusters similar in appearance to soap bubbles.
    • CT scan helps detect parenchymal lesions in individuals with fascioliasis
  • MRI: MRI may be useful in the study of CNS manifestations of trematode infections. MRI can also reveal granuloma of the liver parenchyma in cases of fascioliasis.
  • Cholangiography: In individuals with fascioliasis, this study reveals the multiple cystic dilatations of the ducts. Large cystic dilatation, small cystic ectasias, and mulberrylike dilatation are considered diagnostic of fascioliasis.

Procedures

  • Colonic biopsy: This biopsy is a sensitive and specific procedure to aid in identifying parasite eggs in biopsy specimens for the diagnosis of intestinal schistosomiasis and intestinal trematode infections.
  • Cystoscopy: This procedure is useful to help identify schistosome eggs in mucosal biopsy specimens from the urinary bladder and to exclude other causes of hematuria.

Histologic Findings

Egg granuloma is the typical pathologic lesion in urinary schistosomiasis. These are found in the ureter and urinary bladder. The granuloma consists mainly of eosinophils, macrophages, and lymphocytes surrounding the egg at the center. In chronic infection, fibroblast proliferation and fibrosis are characteristic.

Finger-sized fibrosis in the portal areas is characteristic of S mansoni infection.

Periportal fibrosis, Symmers fibrosis, and perisinusoidal blockage are the typical findings in S japonicum infection.

Adult Paragonimus flukes elicit an acute inflammatory reaction with formation of eosinophilic granulomas and small multiple fibrous cysts in the liver. The eggs also elicit an acute inflammatory reaction consisting of eosinophils, formation of a fibrous capsule, rupture of cysts in bronchioles, eosinophilic empyema, and, finally, calcification. The cystic encapsulation of the eggs in the lung and, less frequently in the brain and in other abdominal organs, is the key pathologic feature in paragonimiasis.

During the acute stage of fascioliasis, the liver is enlarged and exhibits hemorrhagic necrotic tracts in the subcapsular areas infiltrated by eosinophils and other inflammatory cells. In chronic infection, the bile duct exhibits epithelial hyperplasia with minimal pericholangitis and proliferation of tissues.

The infection of the biliary tract by C sinensis, O viverrini, and O felineus demonstrates adenomatous hyperplasia, periductal inflammation, periductal fibrosis, and diffuse or localized dilatation of ducts and may be associated with cholangiocarcinoma in C sinensis.

Ulceration of gut epithelium and localized inflammation are the features of infection caused by F buski and other intestinal flukes.



Medical Care

  • Causes of mortality include recurrent pyogenic cholangitis in persons with schistosomiasis; hemiplegia, cephalgia, and paresis in those with cerebral paragonimiasis; cholangiocarcinoma in those with clonorchiasis; and intercurrent bacterial infections in those with fascioliasis and/or intestinal fluke infections.
  • Praziquantel remains the drug of choice for all trematode infections except fascioliasis, for which bithionol is the drug of choice. Praziquantel is recommended when bithionol is not available.
  • Bithionol is the drug of choice for Fasciola infections.
  • Emetine, dehydroemetine, chloroquine, albendazole, and mebendazole were once used in many trematode infections; however, this practice is now discontinued because these drugs are associated with toxicity and their efficacy is in doubt.
  • When trematode infections are complicated by intercurrent bacterial infections, institute antibiotic therapy.

Surgical Care

  • Surgical management may be needed for complications of trematode infection, which include bladder carcinoma in patients with urinary schistosomiasis, fibrosis and thickening of the intestinal wall in those with intestinal schistosomiasis, ascending cholangitis in those with fascioliasis, and cholangiocarcinoma in those with clonorchiasis.

Consultations

  • Intestinal and liver trematode infections - Infectious diseases specialist
  • Urinary schistosomiasis - Infectious diseases specialist, gastroenterologist, and urologist
  • Pulmonary paragonimiasis - Chest disease specialist
  • Ectopic fluke infections (eg, abdominal and cerebral paragonimiasis; ectopic schistosomiasis in intestine, lung, brain, or spinal cord; ectopic clonorchiasis) - Consultations with appropriate specialists as required per particular manifestations

Diet

  • To prevent paragonimiasis and clonorchiasis, avoid eating raw or undercooked fish.
  • To prevent infection with intestinal flukes and fascioliasis, properly clean and thoroughly wash raw vegetables, watercress, and other water-grown vegetables before eating.
  • Cook water-grown vegetables thoroughly before eating.

Activity

The patient should be given adequate bed rest supplemented with an adequate protein-rich diet.



Chemotherapy objectives in trematode infections are to cure the disease, to reduce morbidity, and to prevent transmission of parasitic infection in endemic areas.

Bithionol (Lorothidol, Bitin) is the drug of choice for Fasciola infections; however, it is an investigational drug with distribution limited to physicians with patients who are unable to take praziquantel. Doses of 30-50 mg/kg/d PO for 5-15 days have been used to treat Fasciola infections. Repeat doses may be administered to some patients. Pediatric patients have been administered the same weight-based dosing used in adults. Adverse effects include nausea, vomiting, diarrhea, and abdominal pain.

Drug Category: Anthelminthics

Parasite biochemical pathways are different enough from the human host to allow selective interference by relatively small doses of chemotherapeutic agents.

Drug NamePraziquantel (Biltricide)
DescriptionDOC in most trematode infections. Safe and effective (less effective against Fasciola infections; reserved for situations in which bithionol is not available).
Increases cell membrane permeability in susceptible worms, resulting in loss of intracellular calcium, massive contractions, and paralysis of musculature. In addition, produces vacuolization and disintegration of schistosome tegument. This is followed by attachment of phagocytes to parasite and death.
Tab should be swallowed whole with some liquid during meals. Keeping tab in mouth may reveal bitter taste, which can produce nausea or vomiting.
Adult DoseSchistosomiasis: S haematobium and S mansoni, 40 mg/kg/d PO tid for 1 d; S japonicum, 60 mg/kg/d PO tid for 1 d
Fasciolopsiasis, metagonimiasis, echinostomiasis, heterophyiasis, and lung trematodes: 15-40 mg/kg PO tid for 1 d
Liver flukes: Fasciolopsis/clonorchiasis, 25 mg/kg PO tid for 1 d
Pediatric Dose<4 years: Not established
>4 years: Administer as in adults
ContraindicationsDocumented hypersensitivity; ocular cysticercosis
InteractionsHydantoins may reduce serum concentrations, possibly leading to treatment failures
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsDestruction of parasite within eyes can cause irreparable lesions (ocular cysticercosis should not be treated with praziquantel); caution while driving or performing other tasks requiring alertness on the day of and following treatment; minimal increases in liver enzymes reported; when schistosomiasis or fluke infection is associated with cerebral cysticercosis, hospitalize patient for duration of treatment



Further Inpatient Care

  • Anemia may be treated with iron supplements and vitamins, which may be administered orally to facilitate iron absorption.

Further Outpatient Care

  • Further outpatient care includes health education. Thorough cooking of fish and aquatic vegetables, fruits, and plants is necessary to prevent ingestion of infective forms of the parasite.

Transfer

  • Transfer if access to specialized health care services is lacking.

Deterrence/Prevention