Trematodes, or flatworms, are a group of helminths that belong to the phylum Platyhelminthes. The adult flatworms share some common characteristics, such as macroscopic size (from one to several centimeters); dorsoventrally flattened, bilaterally symmetric bodies; and two suckers—oral and ventral. Except for schistosomes, which have separate sexes, all human parasitic trematodes are hermaphroditic. Their life cycles involve a mammalian/human definitive host, in which sexual reproduction by adult worms takes place, and an intermediate host (snails), in which asexual multiplication occurs. Some species of trematodes have more than one intermediate host.
Humans are infected either by direct penetration of intact skin (schistosomiasis) or by ingestion of raw freshwater fish, crustaceans, or aquatic plants with metacercariae—the infective larval stage.
Significant trematode infections of humans may be divided according to the location of the adult worms: blood, liver (biliary tree), intestines, or lungs (Table 229-1). Adult worms do not multiply within the mammalian host but can live for up to 30 years. Infections are often chronic.
TABLE 229–1Major Human Trematode Infections ||Download (.pdf) TABLE 229–1 Major Human Trematode Infections
|Trematode ||Transmission Route ||Geographic Distribution |
|Blood Flukes |
|Intestinal schistosomiasis |
|Schistosoma mansoni ||Skin penetration by cercariae released from snails (Biomphalaria spp.) ||Africa, Brazil, Venezuela, Surinam, the Caribbean (low risk) |
|Shistosoma japonicum ||Skin penetration by cercariae released from snails (Oncomelania spp.) ||China, Indonesia, Philippines |
|Schistosoma guineensis and Schistosoma intercalatum ||Skin penetration by cercariae released from snails (Bulinus spp.) ||Rain forest areas of Central Africa |
|Schistosoma mekongi ||Skin penetration by cercariae released from snails (Neotricula aperta) ||Several districts of Cambodia and Lao People’s Democratic Republic (PDR) |
|Urogenital schistosomiasis |
|Schistosoma haematobium ||Skin penetration by cercariae released from snails (Bulinus spp.) ||Africa, Middle East, Corsica (France) |
|Liver Flukes |
|Clonorchis sinensis ||Ingestion of metacercariae in freshwater fish ||Asia, including Republic of Korea, China, Taiwan, Vietnam |
|Opisthorchis viverrini ||Ingestion of metacercariae in freshwater fish ||Northeast Thailand, Lao PDR, Cambodia, Vietnam |
|Opisthorchis felineus ||Ingestion of metacercariae in freshwater fish ||Former Soviet Union, Kazakhstan, Ukraine, Turkey |
|Fasciola hepatica ||Ingestion of metacercariae on aquatic plants or in water ||Worldwide |
|Fasciola gigantica ||Ingestion of metacercariae on aquatic plants or in water ||Africa, Asia |
|Intestinal Flukes |
|Fasciolopsis buski ||Ingestion of metacercariae on aquatic plants ||Bangladesh, China, India, Indonesia, Lao PDR, Malaysia, Taiwan, Thailand, Vietnam |
|Echinostoma spp. ||Ingestion of freshwater fish, frogs, mussels, snails ||China, India, Indonesia, Japan, Malaysia, Russia, Republic of Korea, Philippines, Thailand |
|Heterophyes heterophyes, several other species ||Ingestion of metacercariae in freshwater or brackish-water fish ||Egypt, Greece, Islamic Republic of Iran, Italy, Japan, Republic of Korea, Sudan, Tunisia, Turkey |
|Lung Flukes |
|Paragonimus westermani ||Ingestion of metacercariae in crayfish or crabs ||Tropical and subtropical areas of eastern and southern Asia and sub-Saharan Africa |
|Paragonimus kellicotti ||Ingestion of metacercariae in crayfish or crabs ||North America |
Although it is relatively rare to encounter patients with trematode infections in the United States, many millions of people are infected worldwide. Both schistosomiasis and food-borne trematode infections are poverty-related chronic diseases with high morbidity and a significant public health impact. Various factors may increase the spread of the infections globally. Increasing temperatures may render new areas suitable for the intermediate host snails, and an increase in travel and migration may increase the number of patients with trematode infections—for example, in the United States.
APPROACH TO THE PATIENT Trematode Infection
In the evaluation of a patient in whom trematode infection is suspected, certain questions are highly relevant and can assist in establishing a diagnosis: Where have you been? If you have traveled, when did you return? What activities have you been involved in (trekking, swimming, whitewater rafting)? What have you been eating (local dishes while traveling; raw, poorly cooked, or pickled freshwater fish or crustaceans)? Definitive diagnosis is based on detection of parasite eggs in stool, urine, sputum, and sometimes tissue samples or on serologic tests. The presence of eosinophilia and a history of travel to endemic areas should raise suspicion of trematode infection. The U.S. Centers for Disease Control and Prevention (CDC) can provide guidance with respect to diagnosis and treatment.
Human schistosomiasis is caused by five species of the parasitic genus Schistosoma: S. mansoni, S. japonicum, S. mekongi, and S. intercalatum cause intestinal disease, and S. haematobium causes urogenital disease (Table 229-1). The infection may cause considerable intestinal, hepatic, and genitourinary morbidity. Avian schistosomes may penetrate human skin, but they die in subcutaneous tissue, producing only cutaneous manifestations.
Schistosoma infection is contracted through contact with freshwater bodies harboring infected intermediate-host snails. Cercariae, the infective larval stage released from the snail, penetrate intact human skin within a few minutes after attaching to the skin. After penetration, the cercariae transform to schistosomula, which then enter a small vein or lymphatic vessel, circulate in the bloodstream through the lung capillaries, and are pumped via the heart to all parts of the body to reach the portal vein. There, the worms mature into adult males or females, pair, and migrate to their final location in the mesenteric or pelvic venous plexus.
The interval from cercarial penetration to sexual maturation and egg production, termed the prepatent period, lasts 5–7 weeks (up to 12 weeks for S. haematobium). The female worm then begins to produce eggs, which are excreted via feces or, for S. haematobium, urine. Approximately 50% of eggs are retained in tissue, where they are responsible for organ-specific morbidity (see “Pathogenesis,” below). When excreted eggs reach water, they hatch and release a free-swimming larval stage (miracidium), which, after penetrating a host snail, undergoes several rounds of asexual multiplication. After ~4–6 weeks, infective cercariae are shed from the infected snails into the water. One snail, infected by one miracidium, can shed thousands of cercariae per day for several months; thus the transmission potential of schistosomes is enormous.
The schistosome egg (Fig. 229-1) is the only stage of the parasites’ life cycle that can be detected in humans, either in excreta or in tissue biopsies. The eggs are large and can easily be distinguished morphologically from other helminth eggs. S. haematobium eggs are ~140 mm long, with a terminal spine; S. mansoni eggs are ~150 mm long, with a lateral spine; and S. japonicum eggs are smaller, rounder, and ~90 mm long, with a small lateral spine or knob.
Schistosoma haematobium eggs.
Adult schistosomes are ~1–2 cm long. The male worm is flat, and the body forms a groove or gynecophoric canal in which the mature adult female is held like a sausage in a hotdog roll. Females are longer, thinner, and rounded. The females produce hundreds (African species) to thousands (Asian species) of eggs per day. Each ovum contains a ciliated miracidium larva, which secretes proteolytic enzymes that help the eggs to migrate into the lumen of the bladder (S. haematobium) or the intestine (other species). The lifespan of an adult schistosome averages 3–5 years but can be as long as 30 years. Schistosome worms feed on red blood cells; the debris is regurgitated in the host’s blood, where it can be detected as circulating antigens (see “Diagnosis,” below).
Adult schistosomes persist in the bloodstream for years and have evolved strategies of evading attack using immune effector mechanisms. This immune evasion is a result of several processes, such as binding of host proteins to the schistosome surface, which renders the parasite invisible to the host immune system.
The genome of schistosomes is relatively large (~270 Mb). Whole-genome sequences are available for S. mansoni, S. japonicum, and S. haematobium.
Because of the complex life cycle of schistosomes, with snails as an intermediate host and humans as the final host, transmission is dependent on freshwater habitats that are suitable for the snails, are areas of human activity, and have climatic conditions favoring the survival of the snails and the development of the parasites inside the snail host. These requirements are reflected in the global distribution of schistosomiasis as well as in its microgeographic distribution within an endemic area. For S. mansoni, S. haematobium, and S. intercalatum, humans are the most important definitive host. S. japonicum and S. mekongi are zoonotic parasites, with a wide range of definitive hosts such as pigs, water buffaloes, and various rodents.
It is estimated that 230 million people are infected globally, with ~800 million people living in areas where there is a risk of infection (Fig. 229-2). More than 70% of infected people live in sub-Saharan Africa. Schistosomiasis is the most important of the neglected tropical diseases and is second only to malaria in public health impact. It is a poverty-related disease, and infection is prevalent in areas where adequate water supplies and sanitary facilities are lacking. In these areas, people come into contact with infested water through a variety of activities, including bathing, washing clothes, and collecting water for drinking or cooking. In some areas, adults have a high occupational risk of exposure; fishermen, canal cleaners, and workers in rice fields fall into this category. Among children, playing in water and swimming pose a risk. Large-scale irrigation and hydroelectric power operations can create suitable habitats for host snails and thus increase the risk of schistosomiasis transmission.
Global distribution of human schistosomiasis. A. Schistosoma mansoni infection (dark blue) is endemic in Africa, the Middle East, South America, and a few Caribbean countries. S. intercalatum infection (green) is endemic in sporadic foci in West and Central Africa. B. Schistosoma haematobium infection (purple) is endemic in Africa and the Middle East. The major endemic countries for S. japonicum infection (green) are China, the Philippines, and Indonesia. Schistosoma mekongi infection (red) is endemic in sporadic foci in Southeast Asia. (Reprinted with permission from CH King, AAF Mahmoud: Schistosomiasis and Other Trematode Infections, in DL Kasper et al [eds], Harrison’s Principles of Internal Medicine, 19th ed. New York, McGraw-Hill Education, 2015, pp 1423–1429.)
In general, children living in endemic areas initially acquire infection at ~3–4 years of age—i.e., when they are old enough to walk and come into contact with infested water. However, infection does occur in much younger children. As children grow older, the prevalence and intensity of infection increase, peaking around puberty. A characteristic feature of schistosomiasis infection in human populations is a convex age–prevalence curve, with low prevalence in very young children, higher prevalence in older children with a peak at 10–15 years of age, and declining prevalence in adults. The same pattern is observed between age and intensity of infection and is attributable to various factors. Generally, children have more frequent, prolonged, and extensive water contact than adults through activities like playing and swimming. Furthermore, several studies have indicated that acquired immunity to schistosomiasis develops slowly over several years, so that adults are reinfected to a much lesser extent than children. These factors, combined with progressive spontaneous death of adult worms from infections acquired during childhood, lead to lower levels of infection in the adult population.
Cercarial invasion may be associated with dermatitis arising from dermal and subdermal inflammatory reactions in response to dying cercariae that trigger innate immune responses. However, most manifestations of schistosomiasis—in the acute, established, and chronic phases of infection—are due to immunologic reactions to eggs retained in host tissues.
Around the time when oviposition commences, acute schistosomiasis (Katayama fever) may occur (see “Clinical Features,” below). Antigen excess from eggs results in the formation of soluble immune complexes, which may be deposited in several tissues and initiate a serum sickness–like illness. All evidence suggests that schistosome eggs, and not adult worms, induce the organ-specific morbidity caused by schistosome infections. Approximately half of the eggs are not excreted via feces or urine but are trapped in intestinal or hepatic tissue (S. mansoni, S. japonicum, and S. mekongi) or in the bladder and urogenital system (S. haematobium). The eggs induce a granulomatous host immune response composed primarily of lymphocytes, eosinophils, and alternatively activated macrophages. The lymphocytes produce various TH2 cytokines such as interleukins 4, 5, and 13. Later, in the chronic phase of infection, regulatory cytokines are responsible for immunomodulation or downregulation of host responses to schistosome eggs and play an important role in reducing the size of granulomas.
When S. mansoni or S. japonicum eggs are swept into the small portal branches of the liver via the portal vein, they lodge in the presinusoidal periportal tissues. The formation of granulomas around the eggs can cause significant enlargement of the spleen and liver. High-intensity infections in children are often accompanied by hepatosplenomegaly that generally decreases over time, partly because the number of eggs being deposited in the tissue gradually declines after the early teenage years as partial immunity to new infections develops and partly because of immunologic downregulation of the granulomatous response. However, in some infected individuals, egg-induced granulomatous responses lead to severe periportal fibrosis (Symmers clay pipestem fibrosis), with deposition of collagen around the portal vein, occlusion of the smaller portal branches, and severe, often irreversible, pathology. Occlusion of the portal branches may result in marked portal hypertension.
The signs and symptoms of S. haematobium infection relate to the worms’ predilection for the veins of the urogenital plexus and result from deposition of eggs in the bladder, ureters, and genital organs. During established active infection, clusters of living eggs in the urogenital tissues can be found surrounded by intense inflammatory reactions and intense tissue eosinophilia. Movement of egg clusters into the lumen of the bladder is often followed by sloughing off of the epithelial surface, ulceration, and bleeding. Intense egg-induced tissue inflammation can result in bladder wall thickening and development of masses and pseudopolyps. Inflammation and granuloma formation around the ureteral ostia can lead to hydronephrosis.
Generally, late chronic-stage infections are characterized by accumulation of dead calcified eggs in tissue. Characteristic cervical lesions are found in S. haematobium infections, including active-stage lesions with intense tissue inflammation around live eggs and chronic-stage sandy patches with clusters of calcified eggs.
In general, disease manifestations of schistosomiasis occur in three stages—acute, active, and chronic—according to the duration and intensity of infection.
Cercarial Dermatitis (“Swimmer’s Itch”)
Cercarial penetration of the skin may result in a maculopapular rash called cercarial dermatitis or “swimmer’s itch.” Cercarial dermatitis can develop in people who have not previously been exposed to schistosomiasis (e.g., travelers), whereas it is rare among people living in endemic areas. A particularly severe form of cercarial dermatitis is commonly seen after exposure to cercariae from avian schistosomes. These cercariae cannot complete their development in humans and die in the skin, causing an inflammatory allergic reaction. This form of cercarial dermatitis can occur in people who have been in contact with water from lakes (e.g., in Europe or the United States) where various species of water birds, such as ducks, geese, and swans, are found. The rash may last for 1–2 weeks. This condition normally requires no treatment, but systemic antihistamines or topical antihistamines or glucocorticoids can be used to reduce symptoms.
Acute Schistosomiasis (Katayama Fever)
Symptomatic acute schistosomiasis, also known as Katayama fever or Katayama syndrome, is usually seen in travelers who have contracted the infection for the first time. The onset occurs between 2 weeks and 3 months after exposure to the parasite. The symptoms may appear suddenly and include fever, myalgia, general malaise and fatigue, headache, nonproductive cough, and intestinal symptoms such as abdominal tenderness or pain. Various combinations of these symptoms are often accompanied by eosinophilia and transient pulmonary infiltrates. Many patients recover spontaneously from acute schistosomiasis after 2–10 weeks, but the illness follows a more severe clinical course in some individuals, with weight loss, dyspnea, diarrhea, and hepatomegaly. Severe cerebral or spinal cord manifestations may occur, and even light infections may cause severe illness. The syndrome can, in rare cases, be fatal.
Differential diagnosis includes many other febrile infectious diseases with acute onset, including malaria, salmonellosis, and acute hepatitis. Fever and eosinophilia occur in trichinosis, tropical eosinophilia, invasive ankylostomiasis, strongyloidiasis, visceral larva migrans, and infections with Opisthorchis and Clonorchis species. Katayama fever is rare in people chronically exposed to infection in areas endemic for S. mansoni or S. haematobium.
Intestinal Schistosomiasis (S. mansoni, S. japonicum, S. mekongi)
In intestinal schistosomiasis, adult worms are located in the mesenteric veins, and disease manifestations are associated with parasite eggs passing through or becoming trapped in intestinal tissue. This event induces mucosal granulomatous inflammation with microulcerations, superficial bleeding, and sometimes pseudopolyposis. The symptoms tend to be more pronounced with a high intensity of infection and include intermittent abdominal pain, loss of appetite, and sometimes bloody diarrhea. The clinical manifestations of S. intercalatum and S. mekongi infection are generally milder.
Hepatosplenic schistosomiasis is caused by schistosome eggs trapped in liver tissue and occurs in S. mansoni and S. japonicum infections. There are two distinct clinical entities: early inflammatory hepatosplenomegaly and late hepatosplenic disease with periportal fibrosis.
Early inflammatory hepatosplenic schistosomiasis is the main entity seen in children and adolescents. The liver is enlarged, especially the left lobe, and is smooth and firm. The spleen is enlarged, often extending below the umbilicus, and is firm or hard. Generally, ultrasonography shows no hepatic fibrosis. This form of hepatosplenic schistosomiasis may be found in up to 80% of infected children. Its severity is closely associated with the intensity of infection and may also be associated with concomitant chronic exposure to malaria.
Late hepatosplenic schistosomiasis with periportal or Symmers fibrosis may develop in young and middle-aged adults with long-standing, high-level exposure to infection. Patients with periportal fibrosis may excrete very few or no eggs in feces. During the early stage, the liver is enlarged, especially the left lobe; it is smooth and firm or hard. The spleen is enlarged, often massively, and is firm or hard. The patient may report a left hypochondrial mass with discomfort and anorexia. Ultrasonography reveals typical periportal fibrosis and dilation of the portal vein. Other complications include delayed growth and puberty, especially in S. japonicum infections, and severe anemia. Severe hepatosplenic schistosomiasis may lead to portal hypertension, but hepatic function usually remains normal, even in cases with marked periportal fibrosis and portal hypertension.
Ascites, attributable both to portal hypertension and to hypoalbuminemia, may be seen, especially in S. japonicum infection. Patients with severe hepatosplenic disease and portal hypertension may develop esophageal varices detectable by endoscopy or ultrasound. These patients may experience repeated bouts of hematemesis, melena, or both. Hematemesis is the most severe complication of hepatosplenic schistosomiasis, and death may result from massive loss of blood.
Urogenital Schistosomiasis (S. haematobium)
The signs and symptoms of S. haematobium infection relate to the worms’ predilection for the veins of the urogenital tract. Two stages of infection are recognized. An active stage occurring mainly in children, adolescents, and younger adults is characterized by egg excretion in the urine, with proteinuria and macroscopic or microscopic hematuria and deposition of eggs in the urinary tract. A chronic stage in older individuals is characterized by sparse or no urinary egg excretion despite urogenital tract pathology.
A characteristic sign in the active stage is painless, terminal hematuria. Dysuria and suprapubic discomfort or pain are associated with active urogenital schistosomiasis and may persist throughout the course of active infection. Eggs deposited in the bladder mucosa may give rise to an intense inflammatory response of the bladder wall, which may cause ureteric obstruction and lead to hydroureter and hydronephrosis. These early inflammatory lesions, including obstructive uropathy, can be visualized by ultrasonography.
As the infection progresses, the inflammatory component decreases and fibrosis becomes more prominent. The symptoms at this stage are nocturia, urine retention, dribbling, and incontinence. Cystoscopy reveals “sandy patches” composed of large numbers of calcified eggs surrounded by fibrous tissue and an atrophic mucosal surface. The ureters are less commonly involved, but ureteral fibrosis can cause irreversible obstructive uropathy that can progress to uremia.
Egg deposition may cause granulomas and lesions in the genital organs, most commonly in the cervix and vagina in women and the seminal vessels in men. The results may include dyspareunia, abnormal vaginal discharge, contact bleeding, and lower back pain in women and perineal pain, painful ejaculation, and hematospermia in men. Genital symptoms like bloody discharge and genital itch are associated with S. haematobium infection in school-aged girls living in schistosomiasis-endemic areas. Symptoms such as hematospermia and perineal discomfort have been described in travelers, and eggs have been demonstrated in seminal fluid. An association between female genital schistosomiasis and HIV infection has been demonstrated, but the impact of genital schistosomiasis on HIV transmission needs further elucidation.
S. haematobium has been classified by the International Agency for Research on Cancer (IARC) as definitely carcinogenic to humans (i.e., a group 1 carcinogen). Chronic S. haematobium infection is associated with squamous cell carcinoma of the urinary bladder.
Worms and eggs can sometimes be located in ectopic sites, causing site-specific manifestations and symptoms. Neuroschistosomiasis is one of the most severe clinical forms of schistosomiasis and is caused by the inflammatory response around eggs in the cerebral or spinal venous plexus. S. mansoni and S. haematobium worms can end up in the spinal venous plexus, where they may cause transverse myelitis—an acute complication sometimes seen in travelers returning home with schistosomiasis. S. japonicum is mainly associated with granulomatous lesions in the brain, causing epileptic seizures, encephalopathy with headache, visual impairment, motor deficit, and ataxia. Pulmonary schistosomiasis is caused by portacaval shunting of eggs into the lung capillaries, where they induce granulomas in the perialveolar area. The consequences may be fibrosis, pulmonary hypertension, and cor pulmonale.
Anamnestic information on recent travels to endemic areas and exposure to freshwater bodies through recreational or other activities is important in the diagnosis of schistosomiasis in travelers. Information about exact geographic locations can facilitate identification of the relevant species of Schistosoma. Eosinophilia is a common finding and is often associated with helminthic infections such as schistosomiasis.
Detection of schistosome eggs in stool or urine is indicative of active infection and is the standard diagnostic method. The diagnosis is often based on the detection of eggs in a fixed small amount of excreta—e.g., 50 mg of stool or filtration of 10 mL of urine. This method is widely used among populations in endemic areas and allows quantitation of the level of infection (eggs per gram of feces or per 10 mL of urine). However, levels of egg excretion in people from nonendemic areas may be very low, in which case a larger sample and concentration methods (e.g., formol-ether concentration) may be needed.
Eggs can also be detected in rectal biopsies (both S. mansoni and S. haematobium) and occasionally in Pap smears and semen samples (S. haematobium). Polymerase chain reaction (PCR)–based detection of parasite DNA in stool or urine is more sensitive than parasitologic methods and is increasingly used. Schistosoma DNA can be detected in cerebrospinal fluid samples for diagnosis of neuroschistosomiasis.
Serology, with detection of specific antibodies to schistosomes, is useful in travelers but less so in people from endemic areas where transmission is ongoing. The serologic assays employed at the CDC are a Falcon assay screening test/enzyme-linked immunosorbent assay (FAST-ELISA) using S. mansoni adult microsomal antigen and a confirmatory species-specific immunoblot assay performed in light of the patient’s travel history.
Schistosome proteoglycans—circulating anodic and cathodic antigens (CAAs and CCAs)—regurgitated into the bloodstream by the feeding worms can be detected in serum and urine by ELISA or monoclonal antibody–based lateral flow assays. The presence of CAA or CCA is an indication of active infection, and levels of these antigens correlate well with the intensity of infection. However, detection of CAAs and CCAs is not currently suitable for diagnosis in travelers, who are likely to have low levels of infection and very few worms. A commercially available point-of-care assay (Rapid Medical Diagnostics, Pretoria, South Africa) that detects CCA in urine is now widely used for screening of infected communities in relation to mass drug administration programs.
The drug of choice for treatment of schistosomiasis is praziquantel. It is administered orally, is available as 600-mg tablets, and is effective against all schistosome species infecting humans. The drug is safe and well tolerated. Standard regimens are shown in Table 229-2. In patients who are not cured by initial treatment, the same dose can be repeated at weekly intervals for 2 weeks. Since praziquantel does not affect the young migrating stages of the schistosomes, it may be necessary to repeat the dose 6–12 weeks later, especially if eosinophilia or symptoms persist despite treatment.
As a general principle, all patients with acute schistosomiasis should be treated with praziquantel. Glucocorticoids can be added in Katayama fever to suppress the hypersensitivity reaction. However, treatment for acute schistosomiasis or Katayama fever must be adjusted appropriately for each case, and in the most severe cases management in an acute-care setting is necessary.
Praziquantel is effective in cerebral S. japonicum infections, resulting in rapid dissipation of cerebral edema and resolution of cerebral masses. However, glucocorticoids and anticonvulsants are sometimes needed in neuroschistosomiasis.
The effect of antischistosomal treatment on disease manifestations depends on the stage and severity of the lesions. Early hepatosplenomegaly, mild or moderate fibrosis, and urinary bladder lesions seen during active infection resolve after chemotherapy. However, for late-stage manifestations (e.g., severe fibrosis with portal hypertension), praziquantel treatment is only one component of management, since the main complications are due to obstructive pathology. Management of portal hypertension and prevention of bleeding from esophageal varices should follow clinical guidelines for treatment of these conditions.
TABLE 229–2Treatment of Schistosomiasis and Food-Borne Trematode Infections ||Download (.pdf) TABLE 229–2 Treatment of Schistosomiasis and Food-Borne Trematode Infections
|Infection ||Drug of Choice ||Adult Dosea |
|Schistosoma mansoni, S. haematobium, S. intercalatum, S. guineensis ||Praziquantelb ||40 mg/kg PO in 2 divided doses for 1 day |
|S. japonicum, S. mekongi ||Praziquantel ||60 mg/kg PO in 3 divided doses for 1 day |
|Clonorchis sinensis, Opisthorchis viverrini, Opisthorchis felineus ||Praziquantel ||25 mg/kg PO tid for 2 consecutive days |
|Fasciola hepatica, Fasciola gigantica ||Triclabendazolec ||10 mg/kg PO as a single dosed |
|Fasciolopsis buski ||Praziquantel ||75 mg/kg PO in 3 divided doses for 1 day |
|Echinostoma spp., Heterophyes heterophyes, several other species ||Praziquantel ||25 mg/kg PO tid |
|Paragonimus westermani, Paragonimus kellicotti || |
25 mg/kg PO tid for 2 consecutive days
10 mg/kg PO once (or twice, 12–24 h apart)
Schistosomiasis is contracted through direct contact with infested freshwater. Travelers should be made aware of the risk of infection if they come into contact with freshwater sources in schistosomiasis-endemic areas. For people living in rural areas where schistosomiasis is endemic, it may be very difficult, if not impossible, to avoid water contact—for example, during occupational activities such as fishing and working in rice fields. Schistosomiasis is a poverty-related disease, and access to safe water and good sanitary facilities may rarely be available. Because S. japonicum is a zoonotic parasite, preventive measures should target not only the human population but also animals such as water buffalo, which act as reservoirs for infection.
Praziquantel treatment of infected people, often during mass drug-administration programs, is a cornerstone of the management and control of schistosomiasis. Regular treatment will reduce the level of schistosomiasis morbidity in affected populations. However, treatment should be combined with other relevant strategies, such as control of the intermediate host snails, improved water-quality and sanitation facilities, and health education. Schistosomiasis control measures should be integrated into local health programs.
There have been intensive efforts to develop vaccines, but none is yet available. One vaccine candidate, S. haematobium 28GST, has been tested in a clinical phase 3 trial in populations living in an endemic area.
FOOD-BORNE TREMATODE INFECTIONS
Food-borne trematode infections are a group of zoonotic diseases caused by hepatic, intestinal, and pulmonary parasitic flukes. These infections are contracted by ingestion of infective parasites in undercooked aquatic food or water plants. In 2005, an estimated 56.2 million people were infected with food-borne trematodes and 7.9 million had severe sequelae of these infections.
The most important liver flukes causing human infections are the related species Opisthorchis viverrini and Opisthorchis felineus, which cause opisthorchiasis; Clonorchis sinensis, which causes clonorchiasis; and Fasciola hepatica and Fasciola gigantica, which cause fascioliasis (Table 229-1).
Opisthorchiasis and Clonorchiasis
O. viverrini is found mainly in northeastern Thailand, Laos, and Cambodia; O. felineus mainly in Europe and Asia, including the former Soviet Union; and C. sinensis in Asia, including Korea, China, Taiwan, Vietnam, Japan, and Asian regions of Russia. Parasite eggs excreted from infected humans or animals are ingested by a host snail (the first intermediate host), where they undergo several developmental stages. Cercariae are then released from the snail and penetrate freshwater fish (the second intermediate host), encysting as metacercariae in the muscles or under the scales. Humans become infected by eating raw or undercooked fish from endemic countries. After ingestion, the metacercariae excyst in gastric juices and migrate via the duodenum, the ampulla of Vater, and the extrahepatic biliary system to the intrahepatic bile ducts.
The clinical manifestations of infection with Opisthorchis species and C. sinensis are similar. Pathologic changes are typically seen in the bile ducts, liver, and gallbladder (Table 229-3). Tissue damage and intense inflammation is caused by mechanical and chemical irritation and immune responses to worms or worm products, and chronic inflammation may result in the development of cholangiocarcinoma. Both O. viverrini and C. sinensis are classified by the IARC as definitely carcinogenic (class 1). Acute and light infections are mostly asymptomatic, but hepatitis-like signs and symptoms, with high fever and chills, have been reported, especially in O. felineus infections. In general, only heavily infected people have symptoms and severe complications (Table 229-3).
TABLE 229–3Clinical Features of Food-Borne Trematode Infections ||Download (.pdf) TABLE 229–3 Clinical Features of Food-Borne Trematode Infections
| ||Symptoms or Signs || |
|Infection ||Early or Acute Stage ||Established or Chronic Stage ||Complications |
|Liver Flukes |
|Clonorchis sinensis, Opisthorchis viverrini, Opisthorchis felineus ||Often asymptomatic; sometimes hepatitis-like symptoms and high fever (especially with O. felineus) || |
Biliary colic, cholestatic jaundice, recurrent cholangitis and cholelithiasis; hepatomegaly, gallbladder enlargement, periductal fibrosis.
Light infections are often asymptomatic and remain so for years.
|Pancreatitis, cholangiocarcinomaa |
|Fasciola hepatica, Fasciola gigantica ||Acute onset (1–4 weeks after infection) with high fever, weight loss, sometimes urticaria and liver tenderness ||Biliary colic, cholestatic jaundice, recurrent cholangitis and cholelithiasis; thickening, enlargement, and fibrosis of biliary ducts; sometimes repeated relapses of acute symptoms ||Pancreatitis. In rare cases: ectopic infections in the central nervous system, orbital area, gastrointestinal tract, lungs, and other organs. Rarely, fascioliasis can be fatal. |
|Intestinal Flukes |
|Fasciolopsis buski, Echinostoma spp., Heterophyes heterophyes, several other species ||Often asymptomatic; sometimes nonspecific gastrointestinal symptoms ||Heavy infection may lead to ulceration of intestinal mucosa and malabsorption. Mild infections are often asymptomatic. ||Malnutrition, anemia; rarely, ectopic infection in the central nervous system |
|Lung Flukes |
|Paragonimus westermani, Paragonimus kellicotti ||Often asymptomatic; sometimes insidious onset with anorexia and weight loss ||Bronchitis-, asthma-, and tuberculosis-like symptoms and signs such as chronic cough, dyspnea, bloody (“rusty”) sputum ||Pulmonary cyst formation; ectopic infection in the central nervous system, eyes, skin, heart, abdominal and reproductive organs |
The diagnosis of these infections is based on microscopic identification of parasite eggs in stool specimens. The eggs of Opisthorchis are indistinguishable from those of Clonorchis.
Fascioliasis occurs in many areas of the world and usually is caused by Fasciola hepatica, a common liver fluke of sheep and cattle. F. hepatica is found in more than 50 countries on all continents except Antarctica; F. gigantica is less widespread. The areas with the highest known rates of human Fasciola infection are in the Andean highlands of Bolivia and Peru. In other areas where fascioliasis is found, human cases are sporadic.
Unlike the other liver flukes, Fasciola species have no second intermediate host, as their infectious metacercariae adhere directly to aquatic plants. Humans usually acquire infection by ingesting aquatic plants, such as watercress, that contain viable metacercariae or by drinking water with free metacercariae.
After metacercariae have excysted in the duodenum, Fasciola species migrate through the intestinal wall into the body cavity, penetrate the liver capsule, and move through the liver into the bile ducts. This migration route is different from that of other liver flukes and gives rise to symptoms during the acute migratory phase; the parasites may cause tissue destruction, focal bleeding, and inflammation. Some migrating flukes may deviate from their usual route to cause ectopic infections. In the established latent stage of infection, the parasites may cause bile duct inflammation, resulting in thickening and expansion of the ducts, fibrosis, and ultimately biliary obstruction (Table 229-3). Although some infected people are asymptomatic in the latent phase, others may experience repeated relapses of acute manifestations.
The most widely used diagnostic approach is direct detection of Fasciola eggs by microscopic examination of stool or of duodenal or biliary aspirates. Eggs generally cannot be detected until 3–4 months after exposure, whereas antibodies to the parasite may become detectable 2–4 weeks after exposure. More than one stool specimen may be needed for diagnosis, especially in light infections.
More than 70 species of intestinal flukes can cause human infection. These parasites are found in different geographic areas, with a relatively high prevalence in Southeast Asia. Humans are infected by ingestion of infective metacercariae attached to aquatic plants (Fasciolopsis buski) or encysted in freshwater fish. Flukes mature in the human intestines, and eggs are passed with feces. Mechanical irritation of the intestinal wall and inflammation may lead to nonspecific gastrointestinal symptoms such as diarrhea, constipation, and abdominal pain. Most individuals infected with intestinal flukes are asymptomatic, but heavy infections can be severe, with intestinal mucosal ulcerations and malabsorption (Table 229-3). The diagnosis is established by detection of eggs in stool samples. However, eggs from various intestinal trematodes are often morphologically similar, and it is very difficult to distinguish among species. A cautionary note: Fasciola eggs can be difficult to distinguish on the basis of morphologic criteria from the eggs of the intestinal fluke F. buski. The distinction has implications for therapy: infection with F. buski is treated with praziquantel, which is not effective against fascioliasis (Table 229-2).
Paragonimiasis is a parasitic lung infection caused by lung flukes of the genus Paragonimus. It is a food-borne parasitic zoonosis, with most cases reported from Asia and attributable to consumption of raw or undercooked freshwater crustaceans. Paragonimus westermani and related species (e.g., Paragonimus africanus) are endemic in West Africa, Central and South America, and Asia. The United States has one indigenous species of lung fluke, Paragonimus kellicotti.
Paragonimus species require two intermediate hosts: first, a freshwater snail; and second, a freshwater crustacean, such as a freshwater crab. Humans are infected by consuming raw or undercooked infected crustaceans containing Paragonimus metacercariae. Paragonimus infects other carnivores such as cats, dogs, foxes, rodents, and pigs in addition to humans. After ingestion, metacercariae quickly penetrate the duodenum and traverse the peritoneal cavity, diaphragm, and parietal pleura to mature into hermaphroditic worm pairs in the pleural spaces or lungs within 6–10 weeks. Adults cross-fertilize in cystic cavities in the pleural spaces or lungs within another 4–16 weeks and release unembryonated eggs into bronchioles. The eggs are then coughed up in bloody (“rusty”) sputum and either discharged in sputum or swallowed and later excreted in feces. Unembryonated eggs are passed from the mammalian host into freshwater ecosystems, where they infect intermediate host snails.
The symptoms and signs of paragonimiasis are fever, cough, hemoptysis, and peripheral eosinophilia. Some patients with paragonimiasis and low parasite burdens may remain relatively asymptomatic for prolonged periods or may have recurrent attacks of cough, sputum production, fever, and night sweats that mimic tuberculosis. Infective metacercariae may migrate to extrapulmonary sites such as the brain (cerebral paragonimiasis).
Pulmonary paragonimiasis is diagnosed by detection of parasite ova in sputum and/or feces. Serology can be helpful in egg-negative cases and in cerebral paragonimiasis. Anamnestic information about the consumption of raw or undercooked freshwater crabs by immigrants, expatriates, and returning travelers—and, in the United States, the consumption of raw or undercooked crayfish from freshwater river systems where P. kellicotti is endemic—is important in patients presenting with fever, cough, hemoptysis, pleural effusions, and peripheral eosinophilia.
TREATMENT Food-Borne Trematode Infections
Praziquantel and triclabendazole are the two drugs of choice; Table 229-2 summarizes the dosages recommended for the various trematode infections. All confirmed cases of human paragonimiasis should be treated with praziquantel (Table 229-2) to avoid the complications of extrapulmonary disease. Surgical management may be needed for pulmonary or cerebral lesions.
Drugs are currently the main method of controlling the morbidity associated with food-borne trematode infections, but integrated programs (including improved sanitation; food inspections; and information, education, and communication campaigns) are important for sustainable disease control. Collaboration with other sectors (e.g., agricultural, environmental, and educational) is necessary to tackle highly complex situations in which human behavior, biological factors, and agricultural practices all play a role.
et al: Decline in infection-related morbidities following drug-mediated reductions in the intensity of Schistosoma
infection: A systematic review and meta-analysis. PLoS Negl Trop Dis 11:e0005372, 2017.
J, Van Gompel
A: Schistosomiasis in travellers and migrants. Travel Med Infect Dis 9:6, 2011.
A: Food-borne trematode infections of humans in the United States of America. Parasitol Res 106:1263, 2010.
et al: Global burden of human food-borne trematodiasis: A systematic review and meta-analysis. Lancet Infect Dis 12:210, 2012.
et al (eds): Human Schistosomiasis. CAB International, Wallingford, 1993.
J: Food-borne trematodiases. Clin Microbiol Rev 22:466, 2009.
et al: Liver fluke induces cholangiocarcinoma. PLoS Med 4:e201, 2007.
Additional Online References
et al: A prospective view of animal and human fasciolosis. Parasite Immunol 38:558, 2016.
JH: Paragonimiasis acquired in the United States: Native and nonnative species. Clin Microbiol Rev 26:493, 2013.
PR: Neuroschistosomiasis: Clinical symptoms and pathogenesis. Lancet Neurol 10:853, 2011.
et al: Manifestation, diagnosis, and management of foodborne trematodiasis. BMJ 344:e4093, 2012.
et al: Schistosomiasis-associated pulmonary hypertension: Pulmonary vascular disease: The global perspective. Chest 137:20, 2010.
et al: S. haematobium
as a common cause of genital morbidity in girls: A cross-sectional study of children in South Africa. PLoS Negl Trop Dis 7:e2104, 2013.
et al: Avian schistosomes and outbreaks of cercarial dermatitis. Clin Microbiol Rev 28:165, 2015.
et al: Global status of fish-borne zoonotic trematodiasis in humans. Acta Parasitol 58:231, 2013.
International Agency for Research on Cancer: Opisthorchis viverrini and Clonorchis sinensis, in IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 100. Review of Human Carcinogens. Part B: Biological Agents. Geneva, World Health Organization, 2012, pp 341–371.
International Agency for Research on Cancer: Schistosoma haematobium, in IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 100. Review of Human Carcinogens. Part B: Biological Agents. Geneva, World Health Organization, 2012, pp 371–385.
et al: Reassessment of the cost of chronic helmintic infection: A meta-analysis of disability-related outcomes in endemic schistosomiasis. Lancet 365:1561, 2005.
et al: Association between genital schistosomiasis and HIV in rural Zimbabwean women. AIDS 20:593, 2006.
et al: Classification of the lesions observed in female genital schistosomiasis. Int J Gynaecol Obstet 127:227, 2014.
et al: Drugs treating urinary schistosomiasis. Cochrane Database Syst Rev 8:CD000053, 2014.
et al: Community-based study of genital schistosomiasis in men from Madagascar. Lancet 355:117, 2000.
et al: Schistosomiasis: Water and Sanitation-Related Diseases and the Environment: Challenges, Interventions, and Preventive Measures, Selendy
JMH (ed). Hoboken, NJ, Wiley-Blackwell, 2011, pp 167–174.
et al: Schistosomiasis in the People’s Republic of China: Prospects and challenges for the 21st century. Clin Microbiol Rev 14:270, 2001.
et al: Treatment of schistosomal myeloradiculopathy with praziquantel
and corticosteroids and evaluation by magnetic resonance imaging: A longitudinal study. Clin Infect Dis 39:1618, 2004.
et al: Intestinal trematode infections. Adv Exp Med Biol 766:201, 2014.
et al: Current status and perspectives of Clonorchis sinensis
and clonorchiasis: Epidemiology, pathogenesis, omics, prevention and control. Infect Dis Poverty 5:71, 2016.
et al: Neuroschistosomiasis mansoni: Literature review and guidelines. Neurologist 18:333, 2012.
et al: Advances in the diagnosis of human schistosomiasis. Clin Microbiol Rev 28:939, 2015.