Abdominal parasitic infection

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Abdominal parasitic infection Main page
Overview
Causes
Ascaris lumbricoides
Necator americanus
Giardia lamblia
Fasciola Hepaticum
Schistosoma
Strongyloidis Stercoralis
E. Histolytica (Amebiasis)
Taeniasis
Trichuris trichiura
Hymenolepis Nana

Ascaris lumbricoides

Mode of infection

• Ingestion of eggs secreted in the feces of humans or pigs
• Ingesting uncooked pig or chicken liver bearing larvae of A. suum [13].

Epidemiology and demographics

• Approximately 800 million people are infected [2,5].
• Majority of individuals with ascariasis live in Asia (73 percent), Africa (12 percent), and South America (8 percent); some populations have infection rates as high as 95 percent [2,14].
• Ascariasis is most common among children 2 to 10 years of age, and the prevalence of infection diminishes among individuals >15 years of age. Infections tend to cluster in families [15].

Clinical manifestations

• During the late phase of infection (six to eight weeks after egg ingestion), symptoms of ascariasis may consist of nonspecific symptoms such as abdominal discomfort, anorexia, nausea, vomiting, and diarrhea. Macroscopic adult worms are passed in the stool.
• Intestinal ascariasis should be suspected in patients with nonspecific abdominal symptoms (discomfort, anorexia, nausea, or vomiting) and/or associated complications (biliary or pancreatic involvement) in association with relevant epidemiologic exposure in an area with high prevalence of soil-transmitted helminths. The diagnosis is established via stool microscopy for ova or via examination of adult worms, which may be passed per rectum, coughed up, or passed in urine. (See 'Epidemiology' above and 'Ova and parasite examination' below.)

Complications

• Intestinal obstruction: In endemic areas, 5 to 35 percent of all bowel obstructions are due to ascariasis [22]. Approximately 85 percent of obstructions due to ascariasis occur in children between one and five years of age. The overall incidence of obstruction associated with ascariasis in children is approximately 1 in 500. Obstruction occurs most commonly at the ileocecal valve.
• Migration of adult Ascaris worms into the biliary tree can cause biliary colic, biliary strictures, acalculous cholecystitis, ascending cholangitis, obstructive jaundice, liver abscesses, and bile duct perforation with peritonitis [43-45].

Laboratory findings

• The diagnosis of ascariasis is generally established via stool microscopy for evaluation of Ascaris ova (the eggs of A. lumbricoides and A. suum are indistinguishable). Characteristic eggs may be seen on direct examination of stool or following concentration techniques (picture 2). Eggs of A. lumbricoides and A. suum cannot be distinguished morphologically. Eggs of other parasites may also be detected since coinfection with other parasitic diseases is common.
• Eggs do not appear in the stool until at least 40 days after infection; thus, an early diagnosis cannot be made via stool microscopy, including during the phase of respiratory symptoms.

• Peripheral eosinophilia may be observed during the late phase of infection but is more likely to be observed during the early phase [30].

Imaging findings

• Plain radiography of the abdomen may demonstrate large collections of adult Ascaris worms in heavily infected individuals (particularly in children). The mass of worms contrasts against the gas in the bowel, producing a "whirlpool" effect (image 2) [21]. Plain radiography can also demonstrate intestinal obstruction. (See 'Late phase: Intestinal manifestations'above.)
• Barium swallow may also demonstrate adult Ascaris worms, which manifest as elongated filling defects of the small bowel. The worms may ingest barium; in such cases, the worm's alimentary canal appears as a white thread bisecting the length of the worm's body (image 3) [21].
• Computed tomography (CT) scanning or magnetic resonance imaging (MRI) may demonstrate worms in the bowel. Imaging the worm in cross-section demonstrates a "bull's eye" appearance (image 4). In the setting of hepatobiliary involvement, CT or MRI may demonstrate adult Ascaris worms in the liver or bile ducts. Magnetic resonance cholangiopancreatography (MRCP) may detect adult worms in bile or pancreatic ducts.
• Ultrasonography may demonstrate intestinal echogenic tubular structures, curved strips, or a "target" sign [50]. In some cases, the worms demonstrate curling movements [51,52]. Ultrasonography can also be useful for demonstration of hepatobiliary or pancreatic ascariasis [50-53]; single worms, bundles of worms, or a pseudotumor-like appearance may be seen [53].

Treatment

Drug	Dosage
Albendazole	400 mg orally once
Mebendazole	100 mg orally twice daily for 3 days or 500 mg orally once
Ivermectin	150-200 mcg/kg orally once

Necator americanus

• Approximetly 800 million people are infected with hookworms worldwide [3,5].
• The prevalence of hookworm infection in rural areas of the southeastern United States in the early 20th century was high; extensive control efforts have diminished the prevalence.

Acute gastrointestinal symptoms

• Patients may experience gastrointestinal symptoms at the time of larval migration to the small intestine. Nausea, diarrhea, vomiting, midepigastric pain (usually with postprandial accentuation), and increased flatulence have been observed in individuals with naturally acquired infections [6] and in experimentally infected volunteers [11,12].
• Initial infections may be associated with gastrointestinal symptoms more frequently than subsequent infections. In one individual who was experimentally infected on four occasions, gastrointestinal symptoms and diarrhea were marked with the first infection, mild after the second, and absent after the third and fourth infections [11].
• Gastrointestinal symptoms have been observed to improve following treatment of hookworm infection [13].

Chronic nutritional impairment

• The major impact of hookworm infection is on nutritional status. This is particularly important in endemic areas where children and pregnant women may have limited access to adequate nourishment. In addition, maternal hookworm infection is associated with low birthweight.
• Hookworms cause blood loss during attachment to the intestinal mucosa by lacerating capillaries and ingesting extravasated blood. This process is facilitated by the production of anticoagulant peptides that inhibit activated factor X and factor VIIa/tissue factor complex [14] and inhibit platelet activation [15]. Each N. americanus and A. duodenale worm consumes about 0.3 mL and 0.5 mL of blood per day, respectively. The daily losses of blood, iron, and albumin can lead to anemia and contribute to impaired nutrition, especially in patients with heavy infection [10,16].
• Hookworms also release a serine proteinase inhibitor capable of inhibiting trypsin, chymotrypsin, and pancreatic elastase, leading to impaired digestion, malnutrition, and growth retardation [17].
• Clues to the presence of hookworm infection include clinical manifestations as described above, together with history of skin exposure to potentially contaminated soil and/or otherwise unexplained blood eosinophilia.
• The diagnosis is established by stool examination; there are no reliable serologic tests available.

Stool examination

• Stool examination for the eggs of N. americanus or A. duodenale is useful for detection of clinically significant hookworm infection (picture 1). Fecal egg excretion becomes detectable about eight weeks after dermal penetration of N. americanus infection and up to 38 weeks after dermal penetration of A. duodenale [8]. Stool examination is not helpful prior to established intestinal tract disease, including during early stages of dermal, pulmonary, or intestinal involvement.
• The standard method of diagnosis is with the Kato Katz technique. Other techniques used include the simple sodium nitrate flotation technique (SNF), FLOTAC, and mini-FLOTAC. Microscopic methods of stool examination for detection of hookworm infection are relatively insensitive [18], so serial examinations may be required. Polymerase chain reaction (PCR) tests (including multiplex PCR assays, which can simultaneously detect hookworm, Ascaris lumbricoides, and Trichuris trichiura) have been developed. PCR has superior sensitivity compared with microscopy but has limited commercial accessibility [19-21].
• The eggs of N. americanus and A. duodenale are morphologically indistinguishable. Speciation is not necessary for clinical purposes and is only possible if adult worms are detected in stool or at endoscopy [22,23].
•  Otherwise unexplained eosinophilia may be a major clue to the presence of a parasitic infection. Eosinophilia has been attributed to persistent attachment of adult worms to the intestinal mucosa. Among 128 Indochinese refugees with eosinophilia, a diagnosis of intestinal parasitism was made in 95 percent of cases; hookworm and Strongyloides were the most common organisms (55 and 38 percent, respectively) [24].
• The degree of eosinophilia with hookworm infection is usually mild and varies during the course of the disease. Among experimentally infected volunteers, blood eosinophilia increased progressively after two to three weeks and peaked at five to nine weeks. Peak eosinophil counts ranged from 1350 to 3828 cells/microL [25].
• In untreated infections, eosinophilia slowly diminishes in magnitude but can remain elevated for several years [9].

Treatment

• Iron replacement alone can lead to restoration of a normal hemoglobin level in individuals with hookworm infection, but anemia recurs unless anthelminthic therapy is given.
• Anthelminthic treatment of hookworm infection consists of albendazole (400 mg once on empty stomach) [26,27]. Mebendazole is an acceptable alternative therapy; 100 mg twice daily for three days is more effective than a single dose of 500 mg. In a randomized, controlled trial conducted in China among 314 patients aged ≥5 years, single-dose albendazole had greater efficacy than single-dose mebendazole (69 and 29 percent cure rates, respectively) [28]. Triple-dose therapy had greater efficacy, with cure rates of 92 and 54 percent, respectively [28]. An alternative therapy is pyrantel pamoate (11 mg/kg per day for three days, not to exceed 1 g/day) [26,27,29,30]. Ivermectin has poor efficacy against hookworm.
• Therapy of hookworm infections in patients with marginal nutrition status has beneficial effects on growth, exercise tolerance, and cognitive function [31]. Even in those without impaired nutrition, anthelminthic therapies can improve hemoglobin levels [32].

Giardia lamblia

• High-risk groups include infants, young children, international adoptees, travelers, immunocompromised individuals, and patients with cystic fibrosis [2]. [1].
• The prevalence of giardiasis has been reported to be as high as 20 to 40 percent [1]. The highest rates of infection in resource-limited areas occur among children <5 years.
• Many individuals with G. duodenalis identified in stool samples are asymptomatic, a point highlighted by studies that identified Giardia more commonly in the stool of asymptomatic individuals than among individuals with acute diarrhea [3].
• In the United States in 2012, a total of 15,223 cases were reported [7].
• Transmission of infectious Giardia cysts to humans may occur via three routes: waterborne, foodborne, or fecal-oral transmission [11].
• Water is a major source of giardiasis transmission. Giardia cysts survive readily in mountain streams, as they are hardy in cold water. Water-dwelling mammals, such as beavers, can become infected and may serve as ongoing sources of water contamination [12]. For these reasons, giardiasis is an important cause of diarrheal illness among hikers in wilderness areas who drink water that has not been adequately filtered, treated, or boiled.
• Deep well water is usually safe because filtration of water through soil removes Giardia cysts. Giardia cysts are resistant to chlorination; therefore, bacterial coliform counts are not a reliable measure of Giardia contamination in chlorinated water sources.
• Transmission of giardiasis can occur via ingestion of raw or undercooked food contaminated with cysts or via food that is contaminated after cooking [13,14].
• Person-to-person transmission can occur in settings in which there is fecal incontinence and poor hygiene, such as childcare centers [15]. The risk of acquisition and transmission is greatest for young children who are not yet toilet trained; such children can also serve as a source for secondary cases within households [15].
• Giardiasis can be transmitted via heterosexual or homosexual anal-oral sexual contact [16,17].

Clinical presentation

Asymptomatic infection 

Asymptomatic infection occurs in both children and adults, and asymptomatic cyst shedding can last six months or more [30,31].

It has been observed that in resource-limited settings, most children will have encountered Giardia by age two years without it being associated with diarrhea [32,33].

Acute giardiasis

Symptoms of acute giardiasis include [11]:

●Diarrhea – 90 percent

●Malaise – 86 percent

●Foul-smelling and fatty stools (steatorrhea) – 75 percent

●Abdominal cramps and bloating – 71 percent

●Flatulence – 75 percent

●Nausea – 69 percent

●Weight loss – 66 percent

●Vomiting – 23 percent

●Fever – 15 percent

●Constipation – 13 percent

●Urticaria – 10 percent

Symptoms usually develop after an incubation period of 7 to 14 days. Onset of acute gastrointestinal symptoms within one week of exposure is not likely attributable to infection with Giardia. Symptoms may last two to four weeks.

Chronic giardiasis

Chronic giardiasis may follow the acute phase of illness or may develop in the absence of an antecedent acute illness. Chronic symptoms can develop in up to half of symptomatic individuals [34]. In one study of experimentally infected individuals, 84 percent had a self-limited illness (mean duration 18 days); the remainder became chronically infected.

Symptoms of chronic giardiasis may include:

●Loose stools but usually not diarrhea

●Steatorrhea

●Profound weight loss (10 to 20 percent of body weight)

●Malabsorption

●Malaise

●Fatigue

●Depression

●Abdominal cramping

●Borborygmi

●Flatulence

●Burping

 [35-37].

Complications

In a small number of patients, persistent infection is associated with development of malabsorption and weight loss [38]. Chronic giardiasis may resemble other diseases associated with malabsorption, including inflammatory bowel disease [39]. Some patients may have persistent infection after initial treatment [40].

Chronic giardiasis may affect growth and development in children [32,41,42]. A study among Colombian children suggested that giardiasis was a strong predictor of stunted growth [41]. A longitudinal study including 597 children in Brazil found that growth was impeded among children with giardiasis, even among those with asymptomatic infection [42].

Hypersensitivity phenomena such as rash, urticaria, aphthous ulceration, and reactive arthritis or synovitis have been described in the setting of giardiasis, although these manifestations are rare [34,43].

Laboratory diagnosis

Tools for diagnosis of giardiasis include antigen detection assays, nucleic acid detection assays, and stool examination [45]. In areas where available, antigen or nucleic acid detection tests are preferred over stool examination.

Antigen detection assays 

A number of immunoassays using antibodies against cyst or trophozoite antigens have been developed for stool analysis. Available kits include direct immunofluorescent assays (DFA) that use fluorescein-tagged monoclonal antibodies, immunochromatographic assays, and enzyme-linked immunosorbent assays (ELISAs). In general, these methods have greater sensitivity and faster turn-around time than conventional stool microscopy methods. Specificity and cost are usually relatively comparable. Some studies have shown DFA to have the highest sensitivity [46,47]. Many of the commercially available assays can detect both Giardia and Cryptosporidium simultaneously.

Nucleic acid amplification assays

Nucleic acid amplification assays (NAAT) have been developed to detect Giardia in stool samples [45,52,53]; some remain research tools, though the following are commercially available:

The BioFire FilmArray gastrointestinal panel can detect 22 bacterial, viral, and parasitic (including G. duodenalis) causes of infectious diarrhea [54].

The Luminex xTAG Gastrointestinal Pathogen Panel can detect various viral, bacterial, and protozoan (including G. duodenalis) intestinal pathogens [55,56].

NAATs are of limited use following treatment of infection. One report suggests that Giardia DNA is rapidly cleared after successful treatment [57], although uncertainties remain regarding clearance of Giardia DNA following treatment and whether residual detection might represent killed or viable parasites [53].

NAAT-based tools have also been applied to detect Giardia and other pathogens in water supplies [58].

Stool microscopy

Stool microscopy to detect Giardia can be specific and may also be useful for detecting other potential parasitic causes of gastrointestinal symptoms. Limitations include intermittent excretion of Giardia cysts (necessitating up to three stool exams), cumbersome processing procedures, and technician expertise.

Laboratory processing of stool samples consists of a saline suspension to look for trophozoites and cysts (picture 1) and a polyvinyl alcohol and/or formalin preparation for permanent staining. Loose, watery stool is more likely to be positive for trophozoites; a semiformed or formed stool will likely contain cysts only (picture 2 and picture 3). Giardia can be detected in a single specimen in 50 to 70 percent of cases and in three specimens in 90 percent of cases [59,60].

Treatment

Preferred agents

Preferred agents for initial treatment of giardiasis include tinidazole and nitazoxanide [5,10-16]. For treatment of patients ≥3 years of age, we favor tinidazole since it has a longer half-life than nitazoxanide and may be administered as a single dose with high efficacy (>90 percent). For treatment of patients 12 to 36 months of age, we favor nitazoxanide. Given limited data regarding use of tinidazole and nitazoxanide for patients <12 months of age, we favor metronidazole for these patients. Drug dosing is summarized in the table (table 1).

Antimicrobial resistance has been observed in up to 20 percent of Giardia isolates, and cross-resistance between tinidazole and metronidazole (both are nitroimidazoles) has been observed [13,17-20]. Antimicrobial resistance testing is not routinely available in most clinical settings. In general, presence of persistent or recurrent symptoms should prompt suspicion for antimicrobial resistance; the approach for such cases is discussed below. (See 'Persistent or recurrent symptoms' below.)

Tinidazole

Tinidazole is approved by the US Food and Drug Administration (FDA) for treatment of giardiasis in patients ≥3 years of age; dosing is summarized in the table (table 1) [21,22]. Tinidazole is available only in tablet form. For children unable to swallow tablets, the tablets may be crushed by a pharmacist and mixed with flavored syrup; the suspension should be shaken before use and is good for seven days at room temperature [23].

Tinidazole may be more effective than nitazoxanide; however, heterogeneity across studies and lack of direct comparison in randomized trials precludes comparison of drug efficacy [24]. In one trial including more than 160 children with giardiasis treated with tinidazole (single dose) or nitazoxanide (twice daily for three days), parasitological cure was achieved more frequently among those treated with tinidazole than nitazoxanide (90 versus 78 percent) [25]. As a single-dose regimen, tinidazole is more effective and better tolerated than one or two doses of metronidazole [26].

Side effects of tinidazole include metallic taste (17 percent), nausea, and headache (<3 percent) [24-26]. The drug has been associated with a disulfiram-like effect, so alcohol consumption should be avoided [6,12,27]. To minimize gastrointestinal side effects, tinidazole should be taken with food [28]. (See "Pharmacotherapy for alcohol use disorder", section on 'Disulfiram'.)

Nitazoxanide

Nitazoxanide is approved by the FDA for treatment of giardiasis in patients ≥12 months; dosing is summarized in the table (table 1) [29]. Nitazoxanide is available in liquid and tablet form [28].

A number of trials have shown nitazoxanide to be at least as effective as metronidazole in relieving symptoms in patients with giardiasis; efficacy ranges from 81 to 85 percent [27,30-33]. In addition, nitazoxanide may be effective in treating other intestinal parasites (eg, cryptosporidium and amebiasis) and may shorten the duration of diarrhea attributed to infection even when no pathogen is detected [5,33-36].

Side effects of nitazoxanide include nausea, anorexia, flatulence, increased appetite, enlarged salivary glands, yellow eyes, dysuria, and discolored (bright yellow) urine [27].

Metronidazole

The efficacy of metronidazole for treatment of giardiasis is 75 to 100 percent [13,27,37]. Dosing is summarized in the table (table 1) [5]. Oral metronidazole is available only in tablet form. Metronidazole may be used in infants; for children who are not able to swallow tablets, an oral suspension may be prepared by a compounding pharmacy.

Side effects associated with metronidazole are more common than those associated with tinidazole; they include metallic taste, nausea, gastrointestinal discomfort, and headache. These occur in up to 27 percent of patients [13,26]. Less common effects include leukopenia, dark urine, paresthesia, and dizziness [6]. The drug has been associated with a disulfiram-like effect, so alcohol consumption should be avoided.

Schistosoma

The prevalence of schistosomiasis is highest in sub-Saharan Africa. Worldwide, it has been estimated that more than 200 million people are infected [7,8], and schistosomiasis may cause up to 200,000 deaths annually [9,10].

The geography of schistosomiasis is as follows [11-14]:

S. mansoni occurs in most of sub-Saharan Africa, the western part of South America (mainly Brazil), and some of the South Caribbean islands.

S. haematobium infection occurs in foci throughout sub-Saharan Africa, the Middle East along the Tigris and Euphrates, and southern parts of the Arabian Peninsula. In addition, an outbreak due to a S. haematobium complex species occurred among bathers in the Cavu River in Corsica, France [13].

S. japonicum occurs along the Yangtze River Basin in China, the southern and eastern islands of the Philippines, and in central Sulawesi, Indonesia.●S. intercalatum occurs in limited foci in the Congo, Gabon, and Cameroon in Central Africa.

S. mekongi occurs in the Mekong River Basin (and tributaries) in Laos and Cambodia.

Each human schistosome species requires a specific snail (mollusk) species:

S. mansoni – Biomphalaria spp

S. haematobium and S. intercalatum – Bulinus spp●S. japonicum – Oncomelania spp

S. mekongi – Tricula spp

These snail species require specific environmental conditions and rarely coexist. The distribution of snail species largely defines the local endemicity of the individual schistosome species.

Clinical presentation

Acute schistosomiasis syndrome

Acute schistosomiasis syndrome (known as Katayama fever) is a systemic hypersensitivity reaction to schistosome antigens and circulating immune complexes that occurs three to eight weeks after infection [48]. Acute schistosomiasis occurs at the time of initial infection with S. haematobium, S. mansoni, S. intercalatum, and S. mekongi; it can reappear after subsequent infection with S. japonicum. The onset of clinical manifestations coincides with the beginning of egg production, a period of rapid increase in antigen burden. The syndrome occurs most frequently among nonimmune hosts such as travelers and may be observed in more than half of infected individuals [46,49,50]. Activities associated with acute schistosomiasis syndrome include bathing and swimming in fresh water, scuba diving, water skiing, and rafting [51].

Clinical manifestations of acute schistosomiasis syndrome include sudden onset of fever, urticaria and angioedema, chills, myalgias, arthralgias, dry cough, diarrhea, abdominal pain, and headache [52-56]. Only one or a few of the above symptoms may be observed, and fever is not an essential component of the illness [57]. The symptoms are usually relatively mild and resolve spontaneously over a period of a few days to a few weeks. Occasionally persistent manifestations are observed including weight loss, dyspnea, and chronic diarrhea. In rare cases, neurologic symptoms suggestive of encephalitis can occur [58].

An elevated eosinophil count (>1000/microL) is almost universally present within a few days after onset of symptoms [59]. Patients with cough and/or dyspnea may have patchy infiltrates on chest radiograph [48,56,60].

The treatment of acute schistosomiasis syndrome is discussed separately.

Chronic infection

Chronic infection related to schistosomiasis is most common among individuals in endemic areas with ongoing exposure. However, chronic infection can also occur in individuals with brief exposure such as travelers [51,61,62]. The severity of disease is related to the number of eggs trapped in tissues, their anatomic distribution, the duration and intensity of infection, and the host immune response [17,63].

Symptoms of chronic infection often begin insidiously [20]. The nature of clinical manifestations depends on the organ tropism of the infecting species. Major organs with potential involvement include the intestinal tract, liver, spleen, genitourinary tract, lungs, and central nervous system.

Other clinical manifestations that have been observed in association with schistosomiasis include anemia, malnutrition, growth retardation, and general disability [64,65].

Intestinal schistosomiasis

Intestinal schistosomiasis is caused by infection due to S. mansoni, S. japonicum, S. intercalatum, S. mekongi, and, occasionally, S. haematobium. The most common symptoms include chronic or intermittent abdominal pain, poor appetite, and diarrhea. In heavy infection, chronic colonic ulceration may lead to intestinal bleeding and iron deficiency anemia [66-68]. Intestinal polyps and dysplasia can arise due to granulomatous inflammation surrounding eggs deposited in the bowel wall (picture 1) [69,70]. Bowel strictures can also develop. In rare cases, an inflammatory mass can lead to obstruction or acute appendicitis [71,72].

Hepatosplenic schistosomiasis

• Hepatosplenic schistosomiasis is caused by infection due to S. mansoni, S. japonicum, S. intercalatum, S. mekongi, and, occasionally, S. haematobium. Hepatosplenic schistosomiasis consists of two phases depending on age and duration of infection.
• Among children and adolescents, the predominant pathological process consists of nonfibrotic granulomatous inflammation around trapped eggs in the presinusoidal periportal spaces of the liver. The left liver lobe is enlarged with a sharp edge, and splenomegaly may extend below the umbilicus and into the pelvis in some cases [36,73,74]. There are generally no apparent signs of liver dysfunction. Ultrasonography demonstrates widened periportal spaces, which are more pronounced in heavily infected individuals. At this stage, the changes are largely reversible with treatment [75].
• Among adults with chronic infection (and perhaps genetic predisposition), the predominant pathological process consists of collagen deposition in the periportal spaces, which causes periportal fibrosis (also known as Symmers' pipestem fibrosis) [20,74,76,77]. This leads to occlusion of the portal veins, portal hypertension with splenomegaly, portocaval shunting, and gastrointestinal varices. On physical examination, the liver is firm and nodular. Hepatocellular liver function is not impaired.
• Ultrasonography may demonstrate periportal fibrosis around portal vein tributaries in the setting of late S. japonicum and S. mansoni infections [78-80]. Splenomegaly, portal vein dimensions, and the presence of collateral vessels may also be observed. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrate heterogeneity of hepatic parenchyma, periportal fibrosis, and the presence of venous collateral pathways [81]. At this stage, the changes are only partially reversible with treatment [75]. (See "Noncirrhotic portal hypertension", section on 'Schistosomiasis'.)

Pulmonary complications

• Pulmonary manifestations of schistosomiasis occur most frequently among patients with hepatosplenic disease due to chronic infection with S. mansoni, S. japonicum, or S. haematobium [82]. Development of presinusoidal portal hypertension can lead to development of portosystemic collateral vessels, allowing a path for embolization of schistosome eggs into the pulmonary circulation. Eggs can lodge in pulmonary arterioles (diameter 50 to 100 micrometer) and produce a granulomatous pulmonary endarteritis, with subsequent development of pulmonary hypertension and cor pulmonale [83]. Progression of disease may be associated with cardiac enlargement and pulmonary artery dilatation. These manifestations represent end-stage disease and are generally irreversible.
• Dyspnea is the primary clinical manifestation [84]. Chest radiography demonstrates fine miliary nodules. Echocardiography is useful screening tool for pulmonary hypertension in patients with hepatosplenic schistosomiasis [85].
• In some cases, initiation of antischistosomal therapy may precipitate embolization of adult worms to the lungs, resulting in coughing, wheezing, and pulmonary infiltrates on chest radiography [86]. The mechanism may involve an immunologic response to exposed or released antigens from dead worms [87]. These manifestations are generally self-limited and antischistosomal therapy may be continued.

Genitourinary schistosomiasis

• Genitourinary schistosomiasis is caused by infection due to S. haematobium [88-91]. It can result in infertility and increased risk for HIV transmission.
• In early infection, eggs are excreted in the urine and patients present with microscopic or macroscopic hematuria and/or pyuria [41,92-94]. Blood is usually seen at the end of voiding ("terminal hematuria"), although in severe cases hematuria may be observed for the entire duration of voiding [17]. Men may present with hemospermia [94].
• In early chronic infection, the eggs provoke granulomatous inflammation, ulcerations, and development of pseudopolyps in the vesical and ureteral walls, which may be observed on cystoscopy and mimic malignancy (picture 1) [41,92,93]. Biopsy of such lesions in the setting of suspected malignancy can lead to unexpected visualization of schistosome eggs [95]. Ultrasonography findings of the urinary tract generally correlate well with burden of infection [96]. Urinary tract lesions are largely reversible with treatment prior to onset of fibrosis and calcification [97-100].
• In longstanding infection, dysuria and increased urinary frequency are common symptoms. At this stage, the bladder wall is fibrosed and may calcify, producing a characteristic radiographic image (image 1). Intravenous pyelogram (IVP) may demonstrate ureteral stricture(s). Ultrasonography of the kidneys and bladder may demonstrate bladder wall irregularities due to granulomas. Hydronephrosis, bladder polyps, and tumors can also be detected.
• Bladder neck obstruction, hydroureter, and hydronephrosis can ensue, leading to renal failure [92,95,101,102]. Bacterial superinfection can cause acute pyelonephritis. Longstanding infection may also be associated with development of bladder cancer, particularly in combination with other carcinogenic exposures such as tobacco [103].
• Female genital manifestations may include hypertrophic and ulcerative lesions of the vulva, vagina, and cervix [100,104,105]. Involvement may also include the ovaries or fallopian tubes, which can lead to infertility. Male genital manifestations may include involvement of the epididymis, testicles, spermatic cord, or prostate. Genital lesions may be partially reversible with treatment.

Laboratory findings

• Eosinophilia is observed in 30 to 60 percent of patients [123-125]. Eosinophilia is very common among patients with acute schistosomiasis infection syndrome, a hypersensitivity that occurs most frequently among travelers with new infection [46,57,126]. The degree of eosinophilia depends on the stage, intensity, and duration of infection [127].Eosinophils may be observed in the cerebrospinal fluid (CSF) among patients with neurologic involvement; one review
• including 231 patients with spinal cord involvement noted presence of CSF eosinophils in 41 percent of cases [119].
• Anemia may be observed in patients with blood loss due to chronic intestinal or urinary tract schistosomiasis. A fecal occult blood test may be positive in intestinal schistosomiasis if there is a heavy burden of infection [128].
• Thrombocytopenia may be observed in patients with portal hypertension due to hepatosplenic schistosomiasis secondary to splenic sequestration in an enlarged spleen.
• Liver enzymes are rarely elevated, even in established hepatic fibrosis due to schistosomiasis.
• Hematuria and/or leukocyturia are common in the setting of S. haematobium infection [129-133].

Microscopy

• Identification of schistosome eggs in a stool or urine sample via microscopy is the gold standard for the diagnosis of schistosomiasis. It can also be used for species identification and to measure the parasite burden (picture 1). The sensitivity of microscopy is low in light infections and in acute infection.
• Eggs of S. mansoni, S. japonicum, S. haematobium, S. mekongi, and S. intercalatum can be found in stool (although S. haematobium is principally found in urine). In endemic settings, the Kato-Katz method is a common thick-smear technique using 5 mg of stool examined with a low-power microscope lens; it is relatively easy to perform but lacks sensitivity in light infections. At best, the detection threshold is 20 eggs per gram of stool for a single slide; the Kato-Katz method is good for epidemiologic studies in areas of high endemicity but is not as useful in the setting of light infection in an individual patient.
• Most travel clinics use stool concentration techniques to improve sensitivity to a detection threshold of 10 eggs per gram of stool [13]. The FLOTAC stool concentration method has been proven more sensitive for S. mansoni egg detection than the Kato-Katz and yields at least as good results as the formol-ether extraction techniques, with a detection threshold of two eggs per gram [14]. The mini-FLOTAC method is a further development that can be used in population surveys [15]. Approximately 3000 to 6000 eggs per day must be excreted to reach this detection threshold, which occurs after 6 to 12 weeks following infection. Egg production and detection may be reduced in the setting of malaria chemoprophylaxis with mefloquine or with atovaquone-proguanil [16,17].
• Eggs of S. haematobium are usually found in urine. The sensitivity of urine microscopy is highest for examination of samples collected between 10:00 am and 2:00 pm [18]. Sensitivity can be much improved by examining the precipitate after centrifugation or filtration of urine (minimum volume 10 mL).
• In individuals with pulmonary involvement, eggs may be detected in bronchoscopic washings or transbronchial biopsies [19,20].
• An experienced microscopist can distinguish between viable eggs (containing a living miracidium) and nonviable eggs (empty egg shells) that may be excreted for some time after successful treatment [21]. Eggs can be "hatched" by putting them in water, proving their viability.

Infection intensity

Determining the intensity of infection is important in endemic settings, since parasite burden correlates with the likelihood of complications. The intensity of intestinal schistosomiasis is classified as light (up to 100 eggs per gram), moderate (100 to 400 eggs per gram), or severe (>400 eggs per gram). The intensity of urinary schistosomiasis is classified as light to moderate (up to 50 eggs/10 mL) or severe (>50 eggs/10 mL) [22].

Species morphology

Schistosomiasis eggs have characteristic spines that can be seen on microscopy and usually allow easy species differentiation for the three major species (picture 1). Eggs from schistosome hybrids have been described in endemic populations and travelers [23]. Identification of these aberrant egg morphologies may be more difficult and require parasite genome sequencing [24,25]. Species identification may also be facilitated by epidemiologic information.

Serology

Serologic tests are a useful diagnostic tool in the absence of egg detection via microscopy, particularly for travelers, who generally have a low parasite burden. In general, serologic tests are negative during acute infection and turn positive 6 to 12 weeks or more after exposure [26]. Antibodies are usually detectable before eggs are detectable.

The assays available include ELISA, radioimmunoassay, indirect hemagglutination, Western blot, and complement fixation [27,28]. Serologic tests use a broad array of schistosome antigens including extracts of adult worms, cercarial antigens, or egg extracts such as the S. mansoni soluble egg antigen (SmSEA). Most commercially produced antibody test assays are not species specific; therefore, these assays are generally used as screening tests for schistosome infection.

The sensitivity and specificity are variable and depend on the serologic technique, the antigen used, the stage and the intensity of infection, and the infecting species [29-33]. Sensitivity can be improved by combining the results of two different serological assays targeting distinct antigens, such as adult worm antigen and egg antigen [32-34].

In general, antibody titer does not correlate with parasite burden. A negative antibody test is useful for ruling out infection in endemic settings. None of the tests can distinguish between prior infection and active disease. Antibodies persist for many months to years after successful treatment, so they are not reliable for follow-up [35].

Antigen detection

Techniques to detect parasite antigens are already used qualitatively, but quantitative tests are not yet commercially available and are too expensive to be used as a routine diagnostic tool.

Soluble schistosome antigen titers correlate well with infection intensity and with clinical severity of disease [36-39]. They can also be used to assess treatment efficacy, since loss of excreted antigens indicates cure. Antigen tests become negative 5 to 10 days following successful therapy [39-41].

Two gut-associated schistosome glycoproteins, CAA and CCA, are present in the blood and excreted in the urine during active infection [42-44]. Detection of these water-soluble antigens is a useful way to identify active infection [45]; CAA is detectable early after exposure [43]. In most assays, these antigens are measured via a sandwich ELISA using monoclonal antibodies, which allows quantitation of infection intensity. Sensitivity is high, even when parasite burden is low; the detection threshold is 30 pg CAA/mL serum, which is equivalent to about 10 worm pairs.

Qualitative assays that measure parasite antigens in stool and/or urine have also been developed. A commercially produced urine dipstick test to detect CCA may be a good alternative to the Kato-Katz method to measure spread of infection and posttreatment cure in settings where S. mansoni is endemic [46]. The sensitivity of antigen detection is at least as good as stool or urine concentration methods for egg detection; combining these techniques and/or concentrating these soluble antigens improves sensitivity in low-intensity infections [40,47].

Molecular tests

Molecular testing of specific DNA sequences of the parasite genome via PCR is a promising qualitative diagnostic assay but thus far largely remains a scientific tool. PCR assays for stool, urine, and serum have been developed for diagnosis of schistosomiasis [48-51]. A genus-specific schistosome PCR assay can be combined with PCR assays for other helminths ("multiplex PCR"), with better sensitivity than microscopy [52]. In endemic settings, a PCR assay can measure the parasite burden and can be used as a quantitative test as well [53].

The relative sensitivity and specificity of PCR in early infection and nonendemic settings is uncertain [54]; some assays may be useful for early diagnosis of acute infection [50,51,54-56].

Some PCR assays facilitate species identification [57]. One study of PCR on urine samples noted sensitivity and specificity of 94 and 100 percent, respectively; use of an assay specific for S. mansoni was notable for sensitivity and specificity of 100 and 90 percent, respectively [49]. Another assay for S. haematobium is promising for use with serum, urine, or stool [55]. More elaborate schistosome genome sequencing techniques are also used to determine the epidemiology of schistosome hybrids occasionally found in humans [58].

PCR on cerebrospinal fluid for diagnosis of neuroschistosomiasis may also be useful [59].

Biopsy

Biopsy is useful as a diagnostic tool in the setting of ectopic disease manifestations and in the absence of demonstrative laboratory diagnostic tools.

In the setting of intestinal schistosomiasis, biopsy of rectal or higher intestinal tract mucosa, even in the absence of polyps, may demonstrate characteristic granulomas surrounding eggs embedded in the mucosa (picture 2). Histopathology of superficial rectal biopsies ("rectal snips") is more sensitive than stool microscopy and may demonstrate eggs even when multiple stool specimens are negative. In one study of 135 British expatriates with S. mansoni infection, eggs were detected on rectal biopsy in 61 percent of patients and on stool examination in 39 percent of patients [21].

In the setting of genitourinary schistosomiasis, cystoscopy with bladder biopsy is not needed in most cases but can be performed if the diagnosis is suspected and eggs are not found in urine [60]. Biopsy of urinary tract polyps may demonstrate characteristic granulomas with dramatic eosinophilia surrounding eggs embedded in the mucosa.

Species-specific PCR assays have been used to confirm schistosomiasis as the cause of genital lesions in biopsies and in cytological scrapings [61].

Treatment

Praziquantel

Praziquantel alters the tegument structure of adult worms and increases calcium ion permeability. Calcium ions accumulate in the cytosol, leading to muscular contractions and subsequent paralysis. Damage to the tegument membrane also induces a host immune response to parasite antigens [39]. Therefore, the efficacy of praziquantel depends on both the parasite burden of infection and the host immune defense [40].

Praziquantel is readily absorbed when taken orally with food [9]. Adverse effects of praziquantel occur in approximately one-third of patients and are generally mild. They include dizziness, headache, vomiting, abdominal pain, diarrhea, and pruritus. These symptoms may be attributable to the drug itself and/or to the host immune response to dying parasites. Therefore, adverse effects may be observed more frequently among patients with high parasite burden [41]. Paradoxical hypersensitivity reactions following treatment with praziquantel may be observed among travelers with acute infection and/or in the setting of early chronic schistosomiasis [7,41,42].

Praziquantel is pregnancy category B (table 1) [43-47]. One trial including 370 pregnant women randomized to receive praziquantel or placebo noted no significant differences in safety outcomes including abortion, fetal death in utero, and congenital abnormalities [47]. Praziquantel is excreted in human breast milk, although no adverse effects during lactation have been reported; most favor discontinuation of breastfeeding at the time of treatment and for 72 hours thereafter or delaying treatment until after breastfeeding.

Alternative therapies

Oxamniquine has been used for refractory schistosomiasis infection and may be as effective as praziquantel; it is contraindicated in pregnancy and in general is not as effective as praziquantel [56,57]. Artemisinin derivatives act on the glucose metabolism of immature schistosomes [58] and could be of use in very early infection [6]. Mefloquine has limited action on mature worms. The addition of mefloquine or artesunate to praziquantel is not beneficial [59]. Combination praziquantel with artemether may offer some benefit [60].

PREVENTION

Schistosomiasis control strategies for endemic areas include water sanitation programs, mass treatment, and vaccine development. These and other measures have facilitated eradication of schistosomiasis in Japan and have been adopted as a national strategy in China [61,62].

Minimizing contact with fresh water containing infectious cercarial larvae is an important control measure. Direct contact with fresh water can be reduced by provision of safe water supplies with proper sewage control as well as community education regarding wearing protective clothing and footwear in the setting of freshwater contact [63]. Other measures may include vigorous toweling of exposed skin and/or applying insect repellent DEET (N,N-diethyl-m-toluamide) after exposure to fresh water [64]. Eradication of snail species via molluscicides or environmental control of snail breeding sites has been attempted, although it is difficult to sustain because repopulation can occur rapidly [63,65].