Trematodes

Trematodes 

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.

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 (monoecious). An exception is schistosomes, which are diecious (unisexual).

Classification

The flukes that cause most human infections are  classification of trematodes according to their habitat

Fasciolopsis buski (intestional fluke)

Fasciola hepatica (liver fluke )

 Schistosoma species (blood fluke)

Paragonimus westermani (lung fluke)

Trematode  infections such as schistosomiasis have emerged as important tropical infections. An estimated 200 million people in the tropical belts of the world may have schistosomal infection. This makes Schistosoma  infection the second most prevalent tropical infectious disease in areas such as sub-Saharan Africa after malaria.

Fasciolopis buski (Intestional fluke)

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. Fasciolopsis buski is one of the largest intestinal parasite infecting human beings. This trematode was described for the first time by George Busk in 1843 following autopsy of an Indian sailor in London.

This worm is found mainly in Asia and   the Indian subcontinent, occurring in Taiwan, Thailand, Laos, Bangladesh, India, and   Vietnam. This worm is endemic in Bihar, Maharashtra, Assam and Uttar Pradesh. According to the CDC, Prevalence is approximately 1.9 million people infected with F.  buski in China.  Morbidity is much higher in children, with 57% of children in China infected by Fasciolopsis buski.

Morphology

Adult

Fasciolopsis buski is considered one of the largest trematodes, with the adult form measuring approximately 60 mm in length.  An adult Fasciolopsis buski is shaped like an elongated oval. The adult's length ranges from 20 mm to 75 mm, and has a width up to 20 mm, making it the largest human intestinal fluke. The adult is hermaphroditic.

Fig: Adult Form

Egg

F. buski produce about 25,000 eggs per day, each oval and  measuring approximately 130 mm in length.  These eggs cannot be distinguished from the eggs of Fasciola hepatica.

Fig: Egg

Other morphology forms: Miracidium (ciliated organism), Sporocyst (daughter sporocysts),  Redia (larva) and Cercariae (encyst).

Life cycle of F. busky

Fasciolopsis buski infect both humans and pigs.  After ingestion of the metacercariae, excystation occurs in the duodenum and the organism attaches to the wall of the small intestine where it resides.  The adult form develops in about 3 months and produces unembryonated eggs, which are egested in the feces.  The adults have a life span of about one year. In the water, the eggs become embryonated and release miracidia, which infect the intermediate host, the snail.  Within the snail, the miracidia develop into the sporocyst, rediae and cercariae forms.  Finally, cercariae swim in water until encystment on aquatic plants such as water caltrop, water chestnut (Eliocharis tuberosa), water hyacinth (Eichhornia sp.), water bamboo (Zizania sp.), lotus (Nymphaea lotus), water lily (Nymphaea sp.), watercress, gankola (Otelia sp.), and water morning glory (Ipomoea aquatic). Here, the cercariae undergo encystation to form the metacercariae, which are ingested by the definitive host (pig or human).  The pigs are considered the reservoir host.

Fig: Life-cycle of F. buscy

Pathogenesis

In fasciolopsis busky  , the larvae that escape from their cysts in the duodenum attach themselves to the duodenum or jejunal mucosa within 90 days and developed fully into worm which demage as taumatic, obstructive and toxic. At the sites of attachment the worm cause inflammation and ulceration of  the mucosa. Large number of worms provoke inflammation and ulceration of the mucosa. Large numbers of worms provoke increased secreation of mucosa and  may cause partial obstruction of the bowel. In heavy infection, they may even found attached to the wall of the large bowel. At each point of attachment, there is a local center of inflammation and later ulceration. The immature flukes migrate from the gastrointestinal tract to the liver and biliary tract. Ectopic infections occur in which flukes migrate to the skin or the eye.

Clinical Manifestation   

Many cases are mild or asymptomatic. Clinical symptoms and signs are related to parasite load and include poor appetite, mild abdominal colic, nausea, vomiting, fever, severe epigastric and abdominal pain, diarrhoea or bowel obstruction, acute ileus, anasarca, allergic symptoms,.

The symptoms of more severe infections include abdominal pain, diarrhea, malabsorption, ulceration, hemorrhaging and intestinal obstruction, marked eosinophilia and leucocytosis, malnutrition, vitamin B12 deficiency and generalised toxic symptoms.  It causes considerable morbidity and rarely mortality in the host.

Laboratory Diagnosis

Microcopy

Diagnosis is done primarily through microscopic identification of eggs in stool samples or vomitus; however, Fasciolopis buski eggs cannot be distinguished from the eggs of Fasciola hepatica.  Although the eggs cannot be differentiated, one can determine the type of  infection by the organs affected. F. hepatica infects the liver, while F. buski infects the small intestine.  Occasionally the adult form can be identified in the samples as well.

Fig: Egg of fasciolopsis busky  (bile-stained , oval and  measuring approximately 130 mm in size)

Serology

 Serodiagnosis may be helpful, as in the case of F. buski infections. The coproantigen of F buski in enzyme-linked immunoassay (ELISA) has been introduced as a best procedure. ELISA tests are commonly used and are highly sensitive and specific. 

Since egg  indentification can be difficult, the use of serological tests such as complement fixation and electrophoresis arealso  available. These tests have the   advantage of being positive soon after infection and much earlier than a stool exam. 

                                                          

Others methods

Radiographic imaging studies prove very useful in the diagnosis of fascioliasis. Ultrasound and computed tomography are the most commonly used modalities. Findings include:common bile duct and intrahepatic bile duct dilatation, bile duct wall thickening, nodular lesions, and flukes in the  gallbladder.

Treatment

Praziquantel is the drug of choice for treatment of fasciolopsiasis. Patients are typically treated with praziquantel a drug, which is approved but considered investigational for the treatment of parasites.

Prevention and control

It is advised that people avoiding eating uncooked aquatic plants such as water bamboo and water chestnuts. The control measures in endemic areas should include thorough cooking or steeping of aquatic plants in boiling water, restraining pigs from having access to ponds and canals, eliminating the intermediate snail hosts and prohibiting the use of aquatic green Methods of eradication include proper sanitation and sewage treatment. 

Fasciola hepatica (liver fluke)

F. hepatica is a liver fluke, a term that refers to the flat or rhomboid shape of the adult form of the parasite. Fasciola hepatica infects herbivores (such as sheep, goats, and cattle) as well as humans, who become infected by ingesting contaminated water or plants, including watercress, lettuce, and spinach.

Fasciola 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.  

Fascioliasis, is associated with important economic losses due to mortality; liver condemnation; reduced production of meat, milk, and wool; and expenditures for antihelmintics.  Fascioliasis is also one of the most economically important parasitic diseases of livestock, causing disease in sheep and other domestic animals in Latin America, Africa, Europe, and China. Of the 750 million people who live in endemic areas, over 40 millions are thought to be infected  in total by food-borne trematodes. The disease has a cosmopolitan distribution, with cases reported from Scandinavia to New Zealand and southern Argentina to Mexico.

Morphology

Adult worm- it is a large leaf-shaped fluke, measuring 3cm in length by 1.5 cm in breadth and brown to pale grey in color. There are two suckers, the oral sucker is smaller.The anterior end bearing the oral sucker forms a conical projection.

Fig: Adult worm of F. hepatica

Eggs- Large, operculated, ovoid in shape, brownish yellow in colour (bile-stained). Size 140 μm by 80μm.Contains a large unsegmented ovum in a mass of yolk cells. Excreted with the bile into the duodenum and then passed out along with the faeces.

Fig: Eggs of F. hepatica

Other morphology forms: Miracidium (ciliated organism), Sporocyst (daughter sporocysts),  Redia (larva) and Cercariae (encyst).

Life cycle

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.

Pathogenesis

 Individual adult flukes will attach at various sites to the walls of the bile duct and feed on blood. The multisite feeding pattern in combination with the irritation from the spines on the fluke's cuticle irritate the bile ducts, which cause thickening of the bile duct walls and impairment of liver function. Chronic irritation can actually lead to calcification of the bile duct walls. The presence of a single fluke can lead to infection of the liver and condemnation. If sufficient numbers of flukes are present, they can cause a primary anemia from their blood feeding. Proline, an amino acid produced in large amounts by adult flukes, also intensifies the thickening of the bile duct walls, and there is evidence that proline may also directly cause anemia by destroying red blood cells

Clinical manifestation

F. hepatica is primarily responsible for producing a disease in animals, known as “liver rot”. While in the biliary passages, they may interfere with normal flow of bile , causing obstructive jaundice.

Adult liver flukes in the bile ducts lead to very classical clinical signs: there is loss of condition, progressive weakness, anemia and hypoproteinemia with development of edematous subcutaneous swellings, the  migratory phase have included fever, epigastric and right upper quadrant pain, and urticaria. Leukocytosis,eosinophilia, and mild to moderate anemia are found in many patients. Levels of IgG, IgM, and IgE in serum are usually elevated. The amount of damage depends on the worm burden of the host. Linear lesions of 1 cm or greater can be found.

The main effects are low weight gains in young cattle, decreased milk production and condemnation of infected livers. Overall, the clinical signs of fascioliasis in the live animal could easily be confused with nematode infections.

Laboratory Diagnosis

 Microscopy

Diagnosis of fascioliasis is difficult without high clinical symptoms. Testing the stool for the presence of F. hepatica eggs is useful to establish the diagnosis; however, these eggs are absent in the stool in the acute stage of fascioliasis.  For  microscopic detection of eggs, the numerous methods described (sedimentation- flotation).

Fig : Eggs of F. hepatica  (bile-stained , oval and  measuring approximately 130 mm in size)

Serology

Antibody detection using the enzyme-linked immunosorbent assay (ELISA) has a high sensitivity (98%) in both acute and chronic infections. Many ELISA’s have been described based on complete or subfraction of excretory-secretory (ES) products of F. hepatica.

Copro-antigens DNA-based

Copro-antigen reduction test (CRT) is Succesfully applied.

Others : X-ray of the liver may show tract-like small abscesses and subcapsular lesions. Even with pulmonary symptoms, CXR is rarely rewarding.

Ultrasound of the gall bladder and biliary tract may show adult worms as focal areas of  increased echogenicity. Usually  eosinophilia and probably anaemia seen . ESR may be raised.

Treatment

Although praziquantel is the drug of choice for other trematodes, this agent is ineffective against F. hepatica. The CDC recommends triclabendazole as the first-line agent for the treatment of F.hepatica infection. Dizziness, headache, fever and abdominal pain 5–6 days after the initiation of treatment are the side-effects encountered most commonly. Bithionol is an alternative drug for the treatment of F. hepatica infection.

Prevention and control

The types of control measures depend on the setting (such as epidemiologic, ecologic, and cultural factors). Strict control of the growth and sale of watercress and other edible water plants is important. Human infection can be prevented by the eradication of the disease in animals. The measures consists of treatment of infected animals and destruction of molluscan hosts. No vaccine is available to protect people against Fasciola infection.

Schistosoma mansoni (Blood flukes)

Schistosomiasis, or bilharzia, is a tropical parasitic disease caused by blood-dwelling fluke worms of the genus Schistosoma, from the Greek for skhistos (split) and soma (body). Originally thought to be a single organism with a split body, the parasite was eventually recognized as having male and female forms. 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).

S. japonicum  (transmitted by the amphibious snail Oncomelania and causing intestinal and hepatosplenic schistosomiasis in China, the Philippines, and Indonesia).

Schistosomiasis affects more than 200 million people worldwide.  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. S. mansoni live in the inferior and superior mesenteric veins, respectively. Hence, these flukes are known as blood flukes. Schistosoma mansoni  infects about 83 million people worldwide (data from 1999), causing the disease intestinal schistosomiasis which is the most widespread of the human-infecting schistosomes, and  is present in 54 countries.  These countries are predominantly in South America and the Caribbean, Africa and the Middle East.

  

Morphology

Adult: Unlike other trematodes, schistosomes have separate sexes, but   sometime males and females are found  together. The male is short and holds the relatively long female worm in its gynecophoric canal, a groove like structure.

Egg: S. mansoni producing oval eggs (115-175 x 45-7µm) with a sharp lateral spine

Fig: S. mansoni eggs with wetmount

Life cycle

The parasitic larvae live in fresh water and can penetrate human skin, placing  people at risk through everyday activities such as washing laundry or fetching water. Infection of humans by Schistosoma cercariae, which penetrate human skin and shed their forked tails to become schistosomulae. The schistosomulae migrate through several tissues and stages to their final residence in small veins. Adult worms in humans reside in mesenteric venules in various locations that might be specific for each species. The females deposit eggs in the small venules of the portal and perivesical systems. The eggs are moved progressively toward the lumen of the intestine and are eliminated with feaces or urine. On reaching water, the eggs excreted by an infected person hatch to release a tiny parasite (a miracidium) that swims actively through the water by means of fine hairs (cilia) covering its body. A single miracidium can multiply in the snail to produce nearly 100,000 cercariae. The miracidium survives for about 8–12 hours, during which time it must find and penetrate the soft body of a suitable freshwater snail in order to develop further.  Once inside the snail, the miracidium reproduces many times asexually until thousands of new forms (cercariae) break out of the snail into the water. Depending on the species of snail and parasite, and on environmental conditions, this phase of development may take 3 weeks in hot areas, and 4–7 weeks or longer else where. The fork-tailed cercariae can live for up to 48 hours outside the snail. Within that time they must penetrate the skin of a human being in order to continue their life cycle.

Fig:  Life cycle of S. Mansoni

Pathogenesis

Intestinal schistosomiasis caused by S. mansoni develops more slowly. Larvae mature and develop into adult worms in approximately 3 weeks and  reach the vessels that drain the mesentery. The schistosomula (a larval form)  travels through venous circulation to the heart, lungs, and portal circulation.. At these venous sites, they live and lay eggs for the duration of the host’s life. The smaller number of eggs produced by S. mansoni delay the production of granulomas and lodged in the tissues.The organs and tissues most seriously involved are the colon and rectum but the eggs carried in the mesentric current into portal vessel filter out in the periportal tissue within the liver and setup pathologic process leading to hepatic fibrosis. Children suffer the most from schistosomiasis, which causes poor growth and  impaired cognitive function.

Clinical manifestatioin

Acute schistosomiasis

There is progressive enlargement of  the liver and spleen as well as damage to the intestine, caused by fibrotic lesions around the schistosome eggs lodged in these tissues and hypertension of the abdominal blood vessels. Repeated bleeding from these vessels leads to blood in the stools and can be fatal.

Chronic schistosomiasis

The eggs are mainly produced in the blood vessels around the bowel, symptoms can include bloody diarrhoea and tummy (abdominal) pain which tends to be cramping. Eggs that have not been excreted by the body can also travel to other parts of the body and cause symptoms. For example, your liver, lungs, heart, brain or nervous system may be affected. Symptoms depend on the affected area but can include:

• Breathlessness.
• Cough.
• Palpitations.
• Chest pain.
• Liver failure.
• Seizures.
• Confusion.
• Paralysis (if the spinal cord is involved).

Children who are repeatedly infected with schistosomiasis can develop anaemia, malnutrition and learning difficulties.

Swimmer’s itch

Human skin can be penetrated by cercariae that normally develop in birds. The larvae die in the skin causing an allergic reaction known as swimmer’sitch. This problem is seen in many temperate areas, in people who bathe in fresh, brackish and salt water, where infected aquatic birds shed faeces in water populated by appropriate snail hosts.

Laboratory diagnosis

Microscopy

The diagnosis of intestinal schistosomiasis by counting the eggs in faecal specimens has also been simplified. A small amount of faeces, pressed through a fine nylon or steel screen to remove large debris, and placed under a piece of cellophane soaked in glycerol (Kato technique) or between glass slides (glass sandwich technique) can be quickly examined by trained microscopists.

These species are distinguished from the other  schistosomal species based on the morphology of their eggs and their adult and cercarial forms. S. haematobium eggs have a terminal spine, whereas S. mansoni and   S. japonicum eggs have lateral spines and central spines, respectively. By using the sedimentation technique to concentrate the eggs is said to improve sensitivity.

Serology

When eggs cannot  can be isolated, seroimmunodiagnosis tests can be useful. The use of monoclonal antibodies facilites the detection of Schistosoma 's antigen in blood.

Others

In chronic Schistosomasis, rectal scraping, aspirates, or biopsy via proctoscope may be more rewarding then faecal examination.

Other laboratory findings include anemia and eosinophilia.

Treatment

Praziquantel is effective in a single dose against all forms of schistosomiasis. Previously irreversible damage caused by Schistosoma infections can now be successfully treated with praziquantel. All people are susceptible to infection. Children have a higher rate of reinfection after treatment than adults. Immunization is of great research interest but the probability of success is remote.

Prevention and control

The individual protection from infection (e.g. In travellers) can in principle be achieved by avoiding contact with unsafe water. However, this requires an understanding of the risk of contact with water and a knowledge of the sites where infected snails are likely to occur . The control of the disease is the control  of transmission which is possible by using one or a combination of the  measures likes : improved detection and treatment of sick people; improvement of sanitary facilities for safe and acceptable.

Disposal of human excreta; provision of safe drinking-water; reduction of contact with contaminated water; and snail control.

Paragonimus westermani (Lung flukes) 

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 and  P. westermani, also known as the Oriental lung fluke, is the most widespread species in Africa, South America, and parts of Asia.  Among other species of Paragonimus that have been  reported to cause  human disease from around the world is Paragonimus heterotremus, which has been reported from north eastern parts of the Indian subcontinent.

P. westermani was discovered in the lungs of a human , found eggs in the sputum which recognized in 1879 independently by Manson and Erwin von Baelz in 1880. The species name P. westermani was named after a 1916 and 1922 zookeeper who noted the trematode in a Bengal tiger in an Amsterdam.

Morphology

Adult

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).

Fig:  Adult of P.  westermani

Egg

The average egg size is 85 μm by 53 μm (range, 68-118 μm X 39-67 μm). They are yellow-brown,  ovoidal  or elongate, have a thick shell, and are often asymmetrical with one end slightly flattened.  At the large end, the operculum is clearly visible.

Fig: Egg of P.  westermani

Life cycle

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 stool . 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.

Pathogenesis

As the larvae of P. westermani  penetrate the intestinal wall and localize in the peritoneal cavity there appears to be a considerable migration inside the abdominal cavity before they direct toward the chest cavity through the diaphragm. In the pleural cavity,  the turbid or haemorrhagic exudation containing also numerous pus cells. The diaphragm is another organ that is heavily affected by penetrating larvae and by surrounding intense inflammatory reactions that develop after infection. The worms finally get into the lung parenchyma and induce acute exudative pneumonitis and haemorrhage. They gradually mature and are encysted, thereby producing zones of active inflammation with exudate and of collagenous fibrous tissue. The worms are found usually in pairs. When grown up, these worms are often found inside the bronchial lumen lined with bronchial epithelia of squamous metaplastic character. The cysts consist of the parasite and of dense collagenous connective tissue including various inflammatory cells and eosinophils.

 

Clinical manifestation

The Migration of young worms (acute) may produce diarrhea and abdominal pain. When established in the lungs: Fever, cough, rusty-brown sputum, hemoptysis (often thought to be tuberculosis at first). Migration of worms to other organs(erratic paragonimiasis) can be very severe, particularly when brain is involved. The most remarkable clinical feature is cough and blood-tinged sputum, chest paragonimiasis, cerebral paragonimiasis, abdominal paragonimiasis and generalized paragonimiasis. The clinical symptoms of chest paragonimiasis are haemoptysis in some cases, and quite a few patients complain of difficulty in breathing.

Laboratory diagnosis

Microscopy

Diagnosis is based on microscopic demonstration of eggs in stool or sputum, but these are not present until 2 to 3 months after infection. (Eggs are also occasionally encountered in effusion fluid or biopsy material.) Concentration techniques may be necessary in patients with light infections.

Serology

Antibody Detection

Pulmonary paragonimiasis is the most common presentation of patients infected with Paragonimus spp., although extrapulmonary (cerebral, abdominal) paragonimiasis may occur. Detection of eggs in sputum or feces of patients with paragonimiasis is often very difficult; therefore, serodiagnosis may be very helpful in confirming infections and for monitoring the results of individual chemotherapy. The complement fixation (CF) test has been the standard test for paragonimiasis; it is highly sensitive for diagnosis and for assessing cure after therapy, enzyme immunoassay (EIA) tests were developed as a replacement. The immunoblot (IB) assay performed with a crude antigen extract. Antibody levels detected by EIA and IB do decline after chemotherapeutic cure but not as rapidly as those detected by the CF test.

Other

Biopsy may allow diagnostic confirmation and species identification when an adult or developing fluke is recovered.

Treatment

Praziquantel  is the drug of choice as dosage, 25 mg/kg given orally 3 times per day for 2 consecutive. Alternative drug is Bithionol: adult  or pediatric dosage, 10 mg/kg orally once or twice; or pediatric dosage, 30-50 mg/kg on alternate days for 10-15 doses.

Prevention and control

To improve health education to decrease consumption of undercooked crustaceans   and mass treatment of persons in endemic areas. Never eat raw freshwater crabs or crayfish. Cook crabs and crayfish for to at least 145°F (~63°C). Travelers should be advised to avoid traditional meals containing undercooked freshwater crustaceans.