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==== '''Clinical manifestations''' ====
==== '''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.
* 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''' ====
==== '''Complications''' ====
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==== '''Laboratory findings''' ====
==== '''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.
* 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).  
* 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.  
* Characteristic eggs may be seen on direct examination of stool or following concentration techniques.  


* Peripheral eosinophilia may be observed during the late phase of infection but is more likely to be observed during the early phase [30].
* 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''' ====
==== '''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].
* 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.
* Computed tomography (CT) scanning or magnetic resonance imaging (MRI) may demonstrate worms in the bowel.  
* 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].
* Imaging the worm in cross-section demonstrates a "bull's eye" appearance.  
* 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.


==== '''Treatment''' ====
==== '''Treatment''' ====
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* 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].
* 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].
* 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'''
'''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.
* 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 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'''
* 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.
* Stool examination for the eggs of ''N. americanus'' or ''A. duodenale ''is useful for detection of clinically significant hookworm infection.  
* 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].
* 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].  
* 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].
* Stool examination is not helpful prior to established intestinal tract disease, including during early stages of dermal, pulmonary, or intestinal involvement.
*  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].
* Eosinophilia has been attributed to persistent attachment of adult worms to the intestinal mucosa.
* 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].
* In untreated infections, eosinophilia slowly diminishes in magnitude but can remain elevated for several years [9].


==== Treatment ====
==== 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. [26,27]. 
* 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.
* Mebendazole is an acceptable alternative therapy; 100 mg twice daily for three days is more effective than a single dose of 500 mg.
* 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].
* An alternative therapy is pyrantel pamoate (11 mg/kg per day for three days, not to exceed 1 g/day). [26,27,29,30]


== Giardia lamblia ==
== Giardia lamblia ==
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==== '''Asymptomatic infection''' ====
==== '''Asymptomatic infection''' ====
Asymptomatic infection occurs in both children and adults, and asymptomatic cyst shedding can last six months or more [30,31].
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''' ====
==== '''Acute giardiasis''' ====
Symptoms of acute giardiasis include [11]:
* Symptoms of acute giardiasis include diarrhea, malaise, steatorrhea, abdominal cramps and bloating, nausea, and weight loss.
 
* 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.
●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''' ====
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 oose stools, steatorrhea, profound weight loss, malabsorption, malaise, and fatigue.
 
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''' ====
==== '''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].
* 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].
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.


=== Laboratory diagnosis ===
==== '''Antigen detection assays''' ====
==== '''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.
* 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).  
* 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].


==== '''Nucleic acid amplification assays''' ====
==== '''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:
* Nucleic acid amplification assays (NAAT) have been developed to detect ''Giardia'' in stool samples [45,52,53]; some remain research tools.
 
* The Luminex xTAG Gastrointestinal Pathogen Panel can detect various viral, bacterial, and protozoan (including ''G. duodenalis'') intestinal pathogens [55,56].
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''' ====
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.
* 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''' ===
=== '''Treatment''' ===


===== '''Preferred agents''' =====
===== '''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).
* 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''' =====
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 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].
== Schistosoma ==
* The prevalence of schistosomiasis is highest in sub-Saharan Africa.  
* It has been estimated that more than 200 million people are infected, and schistosomiasis may cause up to 200,000 deaths annually [9,10]


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'.)
=== '''Clinical presentation''' ===


===== '''Nitazoxanide''' =====
===== '''Acute schistosomiasis syndrome''' =====
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].
* 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].


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].
===== '''Chronic infection''' =====
* Chronic infection related to schistosomiasis is most common among individuals in endemic areas with ongoing exposure.
* 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].
'''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'''
* Among adults with chronic infection, 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].
* The predominant pathological process consists of collagen deposition in the periportal spaces, which causes periportal 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.
'''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].
* 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.  


Side effects of nitazoxanide include nausea, anorexia, flatulence, increased appetite, enlarged salivary glands, yellow eyes, dysuria, and discolored (bright yellow) urine [27].
===== '''Genitourinary schistosomiasis''' =====
* 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].
* 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. [41,92,93].
'''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].
* 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].


==== '''Metronidazole''' ====
===== '''Microscopy''' =====
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.
* 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.


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.
===== '''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].


== Schistosoma ==
===== '''Serology''' =====
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 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 geography of schistosomiasis is as follows [11-14]:
===== '''Molecular tests''' =====
* 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].


''S. mansoni'' occurs in most of sub-Saharan Africa, the western part of South America (mainly Brazil), and some of the South Caribbean islands.
===== '''Biopsy''' =====
* Histopathology of superficial rectal biopsies 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].


''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].
=== '''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.


''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.
===== '''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].  
* 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].


''S. mekongi'' occurs in the Mekong River Basin (and tributaries) in Laos and Cambodia.
== Strongyloidis Stercoralis ==
* In tropical and subtropical regions, the overall regional prevalence may exceed 25 percent.  
* The highest rates of infection in the United States are among residents of the southeastern states [3,4] and among individuals who have been in endemic areas.
'''Gastrointestinal symptoms'''


Each human schistosome species requires a specific snail (mollusk) species:
Patients may also experience diarrhea, anorexia, nausea, and vomiting. Epigastric pain may mimic a duodenal ulcer, except that food ingestion may aggravate the pain of strongyloidiasis. Chronic enterocolitis and malabsorption can result from a high intestinal worm burden.


''S. mansoni'' – ''Biomphalaria'' spp
'''Hyperinfection syndrome'''


''S. haematobium'' and ''S. intercalatum'' – ''Bulinus'' spp●''S. japonicum'' – ''Oncomelania'' spp
The most common manifestations of the hyperinfection syndrome include [28,34,37]:


''S. mekongi'' – ''Tricula'' spp
●Fever


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.
●Nausea and vomiting


=== '''Clinical presentation''' ===
●Anorexia


===== '''Acute schistosomiasis syndrome''' =====
●Diarrhea
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].
●Abdominal pain


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].
●Dyspnea


The treatment of acute schistosomiasis syndrome is discussed separately.
●Wheezing


===== '''Chronic infection''' =====
●Hemoptysis
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.
●Cough


Other clinical manifestations that have been observed in association with schistosomiasis include anemia, malnutrition, growth retardation, and general disability [64,65].
=== '''Diagnosis''' ===
* Standard stool examination is notoriously insensitive for detecting ''Strongyloides'' (<50 percent sensitivity) [86].
* Aspiration of duodenojejunal fluid or the use of a string test (Enterotest) is sometimes used to detect ''Strongyloides'' larvae in patients with negative stool samples [85].
* Polymerase chain reaction (PCR) tests have also been developed for detection of ''Strongyloides ''in stool samples and have been found to be more sensitive and more reliable in detection of ''S. stercoralis'' compared with parasitological methods [97,98]. However, PCR tests are not yet widely available.
'''Serology'''
* Diagnosis of strongyloidiasis by enzyme-linked immunosorbent assay (ELISA) has proven useful in immunocompetent individuals, both in symptomatic and asymptomatic strongyloidiasis [99,100]. The ELISA for detecting ''S. stercoralis ''infection detects immunoglobulin (Ig)G to filariform larvae. Negative test results in immunocompetent individuals decrease the likelihood that infection is present; however, some ELISA serologies run by commercial laboratories are of variable reliability. In addition, ELISA results can be falsely negative in immunocompromised hosts [96]. False-positive results may occur in the presence of other helminth infections [90].
'''Endoscopy'''
* Upper endoscopy is not usually needed to establish a diagnosis of strongyloidiasis. However, it may be performed in patients with gastrointestinal symptoms with unsuspected disease. Strongyloidiasis has a broad range of endoscopic features [105]:
* In the duodenum, the findings included edema, brown discoloration of the mucosa, erythematous spots, subepithelial hemorrhages, and megaduodenum.
* In the colon, the findings include loss of vascular pattern, edema, aphthous ulcers, erosions, serpiginous ulcerations, and xanthoma-like lesions.
* In the stomach, thickened folds and mucosal erosions are seen [106].
'''Treatment'''


===== '''Intestinal schistosomiasis''' =====
'''Ivermectin'''
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''' =====
Ivermectin is usually administered as two single 200 mcg/kg doses of ivermectin administered on two consecutive days [109,112].
* 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''' =====
'''Albendazole'''
* 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''' =====
Albendazole (400 mg by mouth on empty stomach twice daily for three to seven days) also has activity against ''Strongyloides'' [113,114]. the efficacy of albendazole has been lower than that of ivermectin, with a mean of 60 percent effectiveness for three days of albendazole versus 92 percent for ivermectin [115].
* 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''' =====
== E. Histolytica (Amebiasis) ==
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.
* Areas with high rates of amebic infection include India, Africa, Mexico, and parts of Central and South America. The overall prevalence of amebic infection may be as high as 50 percent in some areas [3].
* Infection with ''E. dispar'' occurs approximately 10 times more frequently than infection with ''E. histolytica'' [3].  


===== '''Serology''' =====
==== Clinical presentation ====
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 majority of entamoeba infections are asymptomatic; this includes 90 percent of ''E. histolytica''infections.


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.
* Clinical amebiasis generally has a subacute onset, usually over one to three weeks. Symptoms range from mild diarrhea to severe dysentery, producing abdominal pain (12 to 80 percent), diarrhea (94 to 100 percent), and bloody stools (94 to 100 percent), to fulminant amebic colitis. Weight loss occurs in about half of patients, and fever occurs in up to 38 percent. Amebic dysentery is diarrhea with visible blood and mucus in stools and the presence of hematophagous trophozoites (trophozoites with ingested red blood cells) in stools or tissues [24]. Fulminant colitis with bowel necrosis leading to perforation, and peritonitis has been observed in approximately 0.5 percent of cases; associated mortality rate is more than 40 percent. Toxic megacolon can also develop.
* Amebic colitis has been recognized in asymptomatic patients. Among 5193 asymptomatic individuals in Japan undergoing colonoscopy for evaluation of positive fecal occult blood tests, for example, four were found to have amebic ulcerative lesions in the cecum or ascending colon [25].


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].
=== '''Diagnosis''' ===
'''Stool microscopy'''
* The demonstration of cysts or trophozoites in the stool suggests intestinal amebiasis, but microscopy cannot differentiate between ''E. histolytica'' and ''E. dispar'' or ''E. moshkovskii'' strains. In addition, microscopy requires specialized expertise and is subject to operator error [29].
'''Antigen testing'''
* Stool and serum antigen detection assays that use monoclonal antibodies to bind to epitopes present on pathogenic ''E. histolytica'' strains (but not on nonpathogenic ''E. dispar'' strains) are commercially available for diagnosis of ''E. histolytica'' infection [30]. Antigen detection kits using enzyme-linked immunosorbent assay (ELISA), radioimmunoassay, or immunofluorescence have been developed [31-33].
* Antigen detection has many advantages, including ease and rapidity of the tests, capacity to differentiate between strains, greater sensitivity than microscopy, and potential for diagnosis in early infection and in endemic areas (where serology is less useful).
'''Serology'''
* Antibodies are detectable within five to seven days of acute infection and may persist for years.
* Approximately 10 to 35 percent of uninfected individuals in endemic areas have antiamebic antibodies due to previous infection with ''E. histolytica'' [3].
* Negative serology is helpful for exclusion of disease, but positive serology cannot distinguish between acute and previous infection.
'''Molecular methods'''
* Techniques can detect ''E. histolytica'' in stool specimens [32,35,36]. Studies have shown that PCR is significantly more sensitive than microscopy and that it was 100 percent specific for ''E. histolytica'' [37,38].
* PCR is about 100 times more sensitive than fecal antigen tests [39].
'''TREATMENT'''
* All ''E. histolytica'' infections should be treated, even in the absence of symptoms, given the potential risk of developing invasive disease and the risk of spread to family members [1,3].
* The goals of antibiotic therapy of intestinal amebiasis are to eliminate the invading trophozoites and to eradicate intestinal carriage of the organism.


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].
== Taeniasis ==
'''Taeniasis'''


===== '''Antigen detection''' =====
There are two main species of ''Taenia'' for which humans are the only definitive hosts. These are ''Taenia saginata'', the beef tapeworm, and ''Taenia solium'', the pork tapeworm. ''T. saginata ''occurs worldwide but is most common in areas where consumption of undercooked beef is customary, such as Europe and parts of Asia. The third species, ''T. asiatica'', is found among pigs in Taiwan, Korea, China, Vietnam, Indonesia, Thailand, the Philippines, and Japan [1-5]. Concurrent infections with more than one ''Taenia'' species have been described [6].
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].
Issues related to ''T. saginata'' are discussed here. The epidemiology, transmission, clinical manifestations, diagnosis, treatment, and prevention of cysticercosis due to ''T. solium'' are discussed separately. (See "Epidemiology, transmission, and prevention of cysticercosis" and "Clinical manifestations and diagnosis of cysticercosis" and "Treatment of cysticercosis".)


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.
'''Life cycle''' — Humans are the only definitive hosts for ''T. saginata'', ''T. solium'', and ''T. asiatica ''(figure 1). Eggs or gravid proglottids are passed in human stool; eggs can survive for days to months in the environment. Cattle (''T. saginata'') and pigs (''T. solium'' and ''T. asiatica'') become infected by ingesting vegetation contaminated with eggs or gravid proglottids. In the animal's intestine, the oncospheres hatch, invade the intestinal wall, and migrate hematogenously to striated muscles, where they develop into cysticerci. Cysticercus contains protoscolices; they usually measure 5 by 10 mm and can survive for several years in the animal.


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].
Humans become infected by ingesting raw or undercooked infected meat containing cysticerci. In the human intestine, protoscolices are released from the cysts and attach to the intestinal wall via suckers and hooks. Each protoscolex can become the head of an adult tapeworm, which develops by forming proglottids that arise from the caudal end of the scolex; this occurs over about two months, and the adult tapeworm can survive for years in the small intestine. Most human infections are with only one or a few adult tapeworms.


===== '''Molecular tests''' =====
The length of an adult worm is usually ≤5 m for ''T. saginata'' (however, it may reach up to 25 m) and 2 to 7 m for ''T. solium''. The adult worms produce proglottids that mature, become gravid, detach from the tapeworm, and are passed in the stool (approximately six per day). ''T. saginata ''adult worms usually have 1000 to 2000 proglottids, while ''T. solium'' adult worms have an average of 1000 proglottids. The eggs in the gravid proglottids are released after the proglottids are passed in the stool. ''T. saginata'' may produce up to 100,000 eggs per proglottid, and ''T. solium'' may produce 50,000 eggs per proglottid.
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].
'''Clinical manifestations''' — Most human carriers of adult tapeworms are asymptomatic. Intermittently, patients may pass proglottids in the stool (''T. solium'') or spontaneously (''T. saginata'') or may notice segments in their stool or sense the movement of proglottids through the anus. There may be associated symptoms including nausea, anorexia, or epigastric pain. Anxiety, headache, dizziness, and urticaria can also occur. A peripheral eosinophilia (up 15 percent) may be observed.


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].
Occasionally, segments can enter the appendix, common bile duct, or pancreatic duct and cause obstruction [7,8]. Rarely, proglottids can be aspirated or regurgitated.


PCR on cerebrospinal fluid for diagnosis of neuroschistosomiasis may also be useful [59].
'''Diagnosis''' — The diagnosis is generally established by identifying eggs or proglottids in the stool. The eggs of ''Taenia'' species are morphologically indistinguishable (picture 1); they are round with a double-walled, radially striated membrane and measure 30 to 40 micrometers. ''T. saginata'' eggs have an acid-fast shell; ''T. solium'' eggs are not acid fast.


===== '''Biopsy''' =====
The proglottids and scolices of ''T. solium'' and ''T. saginata ''are morphologically distinguishable and can be used to establish a species diagnosis (picture 2 and picture 3). The ''T. saginata'' proglottids have 12 or more primary uterine branches; ''T. solium''proglottids have ≤10. These branches can be seen on direct examination or by injecting India ink into the segment via its lateral genital opening.
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].
The scolex usually remains in the intestine when proglottids are passed; it is rare for the entire worm to be eliminated spontaneously. Following antiparasitic therapy, however, the scolex of a fully evacuated worm may be identified in the stool. ''T. saginata'' has a scolex with four lateral suckers and no hooks ("unarmed"). ''T. solium'' has a scolex with a well-developed rostellum (crown) that has four suckers and a double row of hooks ("armed").


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.
The sensitivity of stool examination is limited since elimination of eggs and proglottids is intermittent. To increase the diagnostic yield, repeat specimens should be examined, and concentration techniques can be used. In addition, ''T. saginata'' eggs may be deposited on perianal areas and be detected by anal swabs.


Species-specific PCR assays have been used to confirm schistosomiasis as the cause of genital lesions in biopsies and in cytological scrapings [61].
Laboratory workers must exercise caution when performing stool examinations; ''T. solium'' eggs are infectious if ingested [9,10]. (See "Clinical manifestations and diagnosis of cysticercosis".)


=== '''Treatment''' ===
Immunologic and molecular methods have been developed to improve diagnostic sensitivity, including an enzyme-linked immunosorbent assay (ELISA) for the detection of ''T. solium'' antigens in fecal samples and DNA hybridization techniques for the detection of eggs in stools [11-17]. In addition, several polymerase chain reaction (PCR) assays targeting various genomic regions have been developed for distinguishing between species of human ''Taenia'' infections, including PCR-restriction fragment length polymorphism (RFLP) methods [18,19], species-specific DNA probes [14], loop-mediated isothermal amplification (LAMP) [20-22], and nested/multiplex PCR [23-27]. Primers targeting the mitochondrial cytochrome c oxidase subunit 1 (''cox1'') gene of the three ''Taenia'' species have been developed and show promise for more routine use to distinguish between the three ''Taenia'' species [5]. In general, these assays are not yet suitable for routine diagnosis or field studies and are not widely available.
'''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.
Diagnosis of taeniasis has also been made by visualizing the worm on capsule endoscopy [28].


===== '''Alternative therapies''' =====
Praziquantel is the treatment of choice for all of the tapeworm infections discussed above [41,42]. Dosing depends upon the species [43]. Dosing for taeniasis and diphyllobothriasis is 5 to 10 mg/kg orally (single dose), although excellent efficacy against ''T. saginata'' infections has been reported at doses as low as 2.5 mg/kg [44]. Dosing for hymenolepiasis is 25 mg/kgorally (single dose), followed by repeat dose 10 days later.
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'''
Praziquantel is a synthetic heterocyclic isoquinolone-pyrazine derivative that induces ultrastructural changes in the teguments of parasites, resulting in increased permeability to calcium ions. Calcium ions accumulate in the parasite cytosol, leading to muscular contractions and ultimate paralysis of adult worms [45]. By damaging the tegument membrane, praziquantel also exposes parasite antigens to host immune responses [46]. These effects lead to dislodgement of worms from their intestinal sites and subsequent expulsion by peristalsis.


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].
Niclosamide is an acceptable alternative treatment for tapeworms if praziquantel is not available. Niclosamide comes in 500 mg tablets that need to be chewed; it is not available in the United States. Dosing consists of four tablets (500 mg) in a single dose (2 g) for adults, two tablets (1 g) for children 11 to 34 kg, and three tablets (1.5 g) for children >34 kg.


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].
Nitazoxanide has been used to treat hymenolepiasis with 75 to 85 percent efficacy [47,48]. Dosing consists of 500 mg twice daily for three days for patients >11 years of age, 200 mg twice daily for three days for patients 4 to 11 years of age, and 100 mg twice daily for three days for patients 1 to 3 years of age [47,48].


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}

Revision as of 17:51, 30 January 2018


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

Overview

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.

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.
  • 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

  • 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.
  • 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.

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].

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].

Stool examination

  • Stool examination for the eggs of N. americanus or A. duodenale is useful for detection of clinically significant hookworm infection.
  • 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.
  • Eosinophilia has been attributed to persistent attachment of adult worms to the intestinal mucosa.
  • In untreated infections, eosinophilia slowly diminishes in magnitude but can remain elevated for several years [9].

Treatment

  • Anthelminthic treatment of hookworm infection consists of albendazole. [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.
  • An alternative therapy is pyrantel pamoate (11 mg/kg per day for three days, not to exceed 1 g/day). [26,27,29,30]

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].

Acute giardiasis

  • Symptoms of acute giardiasis include diarrhea, malaise, steatorrhea, abdominal cramps and bloating, nausea, and weight loss.
  • 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

Symptoms of chronic giardiasis may include oose stools, steatorrhea, profound weight loss, malabsorption, malaise, and fatigue.

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].

Laboratory diagnosis

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).
  • 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].

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

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.

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).
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].

Schistosoma

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

Clinical presentation

Acute schistosomiasis syndrome
  • 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].
Chronic infection
  • Chronic infection related to schistosomiasis is most common among individuals in endemic areas with ongoing exposure.
  • 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].

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

  • Among adults with chronic infection, 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].
  • The predominant pathological process consists of collagen deposition in the periportal spaces, which causes periportal 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.

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].
  • 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.
Genitourinary schistosomiasis
  • 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].
  • 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. [41,92,93].

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].
  • 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.
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].
Serology
  • 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.
Molecular tests
  • 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].
Biopsy
  • Histopathology of superficial rectal biopsies 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].

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.
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].
  • 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].

Strongyloidis Stercoralis

  • In tropical and subtropical regions, the overall regional prevalence may exceed 25 percent.
  • The highest rates of infection in the United States are among residents of the southeastern states [3,4] and among individuals who have been in endemic areas.

Gastrointestinal symptoms

Patients may also experience diarrhea, anorexia, nausea, and vomiting. Epigastric pain may mimic a duodenal ulcer, except that food ingestion may aggravate the pain of strongyloidiasis. Chronic enterocolitis and malabsorption can result from a high intestinal worm burden.

Hyperinfection syndrome

The most common manifestations of the hyperinfection syndrome include [28,34,37]:

●Fever

●Nausea and vomiting

●Anorexia

●Diarrhea

●Abdominal pain

●Dyspnea

●Wheezing

●Hemoptysis

●Cough

Diagnosis

  • Standard stool examination is notoriously insensitive for detecting Strongyloides (<50 percent sensitivity) [86].
  • Aspiration of duodenojejunal fluid or the use of a string test (Enterotest) is sometimes used to detect Strongyloides larvae in patients with negative stool samples [85].
  • Polymerase chain reaction (PCR) tests have also been developed for detection of Strongyloides in stool samples and have been found to be more sensitive and more reliable in detection of S. stercoralis compared with parasitological methods [97,98]. However, PCR tests are not yet widely available.

Serology

  • Diagnosis of strongyloidiasis by enzyme-linked immunosorbent assay (ELISA) has proven useful in immunocompetent individuals, both in symptomatic and asymptomatic strongyloidiasis [99,100]. The ELISA for detecting S. stercoralis infection detects immunoglobulin (Ig)G to filariform larvae. Negative test results in immunocompetent individuals decrease the likelihood that infection is present; however, some ELISA serologies run by commercial laboratories are of variable reliability. In addition, ELISA results can be falsely negative in immunocompromised hosts [96]. False-positive results may occur in the presence of other helminth infections [90].

Endoscopy

  • Upper endoscopy is not usually needed to establish a diagnosis of strongyloidiasis. However, it may be performed in patients with gastrointestinal symptoms with unsuspected disease. Strongyloidiasis has a broad range of endoscopic features [105]:
  • In the duodenum, the findings included edema, brown discoloration of the mucosa, erythematous spots, subepithelial hemorrhages, and megaduodenum.
  • In the colon, the findings include loss of vascular pattern, edema, aphthous ulcers, erosions, serpiginous ulcerations, and xanthoma-like lesions.
  • In the stomach, thickened folds and mucosal erosions are seen [106].

Treatment

Ivermectin

Ivermectin is usually administered as two single 200 mcg/kg doses of ivermectin administered on two consecutive days [109,112].

Albendazole

Albendazole (400 mg by mouth on empty stomach twice daily for three to seven days) also has activity against Strongyloides [113,114]. the efficacy of albendazole has been lower than that of ivermectin, with a mean of 60 percent effectiveness for three days of albendazole versus 92 percent for ivermectin [115].

E. Histolytica (Amebiasis)

  • Areas with high rates of amebic infection include India, Africa, Mexico, and parts of Central and South America. The overall prevalence of amebic infection may be as high as 50 percent in some areas [3].
  • Infection with E. dispar occurs approximately 10 times more frequently than infection with E. histolytica [3].

Clinical presentation

  • The majority of entamoeba infections are asymptomatic; this includes 90 percent of E. histolyticainfections.
  • Clinical amebiasis generally has a subacute onset, usually over one to three weeks. Symptoms range from mild diarrhea to severe dysentery, producing abdominal pain (12 to 80 percent), diarrhea (94 to 100 percent), and bloody stools (94 to 100 percent), to fulminant amebic colitis. Weight loss occurs in about half of patients, and fever occurs in up to 38 percent. Amebic dysentery is diarrhea with visible blood and mucus in stools and the presence of hematophagous trophozoites (trophozoites with ingested red blood cells) in stools or tissues [24]. Fulminant colitis with bowel necrosis leading to perforation, and peritonitis has been observed in approximately 0.5 percent of cases; associated mortality rate is more than 40 percent. Toxic megacolon can also develop.
  • Amebic colitis has been recognized in asymptomatic patients. Among 5193 asymptomatic individuals in Japan undergoing colonoscopy for evaluation of positive fecal occult blood tests, for example, four were found to have amebic ulcerative lesions in the cecum or ascending colon [25].

Diagnosis

Stool microscopy

  • The demonstration of cysts or trophozoites in the stool suggests intestinal amebiasis, but microscopy cannot differentiate between E. histolytica and E. dispar or E. moshkovskii strains. In addition, microscopy requires specialized expertise and is subject to operator error [29].

Antigen testing

  • Stool and serum antigen detection assays that use monoclonal antibodies to bind to epitopes present on pathogenic E. histolytica strains (but not on nonpathogenic E. dispar strains) are commercially available for diagnosis of E. histolytica infection [30]. Antigen detection kits using enzyme-linked immunosorbent assay (ELISA), radioimmunoassay, or immunofluorescence have been developed [31-33].
  • Antigen detection has many advantages, including ease and rapidity of the tests, capacity to differentiate between strains, greater sensitivity than microscopy, and potential for diagnosis in early infection and in endemic areas (where serology is less useful).

Serology

  • Antibodies are detectable within five to seven days of acute infection and may persist for years.
  • Approximately 10 to 35 percent of uninfected individuals in endemic areas have antiamebic antibodies due to previous infection with E. histolytica [3].
  • Negative serology is helpful for exclusion of disease, but positive serology cannot distinguish between acute and previous infection.

Molecular methods

  • Techniques can detect E. histolytica in stool specimens [32,35,36]. Studies have shown that PCR is significantly more sensitive than microscopy and that it was 100 percent specific for E. histolytica [37,38].
  • PCR is about 100 times more sensitive than fecal antigen tests [39].

TREATMENT

  • All E. histolytica infections should be treated, even in the absence of symptoms, given the potential risk of developing invasive disease and the risk of spread to family members [1,3].
  • The goals of antibiotic therapy of intestinal amebiasis are to eliminate the invading trophozoites and to eradicate intestinal carriage of the organism.

Taeniasis

Taeniasis

There are two main species of Taenia for which humans are the only definitive hosts. These are Taenia saginata, the beef tapeworm, and Taenia solium, the pork tapeworm. T. saginata occurs worldwide but is most common in areas where consumption of undercooked beef is customary, such as Europe and parts of Asia. The third species, T. asiatica, is found among pigs in Taiwan, Korea, China, Vietnam, Indonesia, Thailand, the Philippines, and Japan [1-5]. Concurrent infections with more than one Taenia species have been described [6].

Issues related to T. saginata are discussed here. The epidemiology, transmission, clinical manifestations, diagnosis, treatment, and prevention of cysticercosis due to T. solium are discussed separately. (See "Epidemiology, transmission, and prevention of cysticercosis" and "Clinical manifestations and diagnosis of cysticercosis" and "Treatment of cysticercosis".)

Life cycle — Humans are the only definitive hosts for T. saginata, T. solium, and T. asiatica (figure 1). Eggs or gravid proglottids are passed in human stool; eggs can survive for days to months in the environment. Cattle (T. saginata) and pigs (T. solium and T. asiatica) become infected by ingesting vegetation contaminated with eggs or gravid proglottids. In the animal's intestine, the oncospheres hatch, invade the intestinal wall, and migrate hematogenously to striated muscles, where they develop into cysticerci. Cysticercus contains protoscolices; they usually measure 5 by 10 mm and can survive for several years in the animal.

Humans become infected by ingesting raw or undercooked infected meat containing cysticerci. In the human intestine, protoscolices are released from the cysts and attach to the intestinal wall via suckers and hooks. Each protoscolex can become the head of an adult tapeworm, which develops by forming proglottids that arise from the caudal end of the scolex; this occurs over about two months, and the adult tapeworm can survive for years in the small intestine. Most human infections are with only one or a few adult tapeworms.

The length of an adult worm is usually ≤5 m for T. saginata (however, it may reach up to 25 m) and 2 to 7 m for T. solium. The adult worms produce proglottids that mature, become gravid, detach from the tapeworm, and are passed in the stool (approximately six per day). T. saginata adult worms usually have 1000 to 2000 proglottids, while T. solium adult worms have an average of 1000 proglottids. The eggs in the gravid proglottids are released after the proglottids are passed in the stool. T. saginata may produce up to 100,000 eggs per proglottid, and T. solium may produce 50,000 eggs per proglottid.

Clinical manifestations — Most human carriers of adult tapeworms are asymptomatic. Intermittently, patients may pass proglottids in the stool (T. solium) or spontaneously (T. saginata) or may notice segments in their stool or sense the movement of proglottids through the anus. There may be associated symptoms including nausea, anorexia, or epigastric pain. Anxiety, headache, dizziness, and urticaria can also occur. A peripheral eosinophilia (up 15 percent) may be observed.

Occasionally, segments can enter the appendix, common bile duct, or pancreatic duct and cause obstruction [7,8]. Rarely, proglottids can be aspirated or regurgitated.

Diagnosis — The diagnosis is generally established by identifying eggs or proglottids in the stool. The eggs of Taenia species are morphologically indistinguishable (picture 1); they are round with a double-walled, radially striated membrane and measure 30 to 40 micrometers. T. saginata eggs have an acid-fast shell; T. solium eggs are not acid fast.

The proglottids and scolices of T. solium and T. saginata are morphologically distinguishable and can be used to establish a species diagnosis (picture 2 and picture 3). The T. saginata proglottids have 12 or more primary uterine branches; T. soliumproglottids have ≤10. These branches can be seen on direct examination or by injecting India ink into the segment via its lateral genital opening.

The scolex usually remains in the intestine when proglottids are passed; it is rare for the entire worm to be eliminated spontaneously. Following antiparasitic therapy, however, the scolex of a fully evacuated worm may be identified in the stool. T. saginata has a scolex with four lateral suckers and no hooks ("unarmed"). T. solium has a scolex with a well-developed rostellum (crown) that has four suckers and a double row of hooks ("armed").

The sensitivity of stool examination is limited since elimination of eggs and proglottids is intermittent. To increase the diagnostic yield, repeat specimens should be examined, and concentration techniques can be used. In addition, T. saginata eggs may be deposited on perianal areas and be detected by anal swabs.

Laboratory workers must exercise caution when performing stool examinations; T. solium eggs are infectious if ingested [9,10]. (See "Clinical manifestations and diagnosis of cysticercosis".)

Immunologic and molecular methods have been developed to improve diagnostic sensitivity, including an enzyme-linked immunosorbent assay (ELISA) for the detection of T. solium antigens in fecal samples and DNA hybridization techniques for the detection of eggs in stools [11-17]. In addition, several polymerase chain reaction (PCR) assays targeting various genomic regions have been developed for distinguishing between species of human Taenia infections, including PCR-restriction fragment length polymorphism (RFLP) methods [18,19], species-specific DNA probes [14], loop-mediated isothermal amplification (LAMP) [20-22], and nested/multiplex PCR [23-27]. Primers targeting the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of the three Taenia species have been developed and show promise for more routine use to distinguish between the three Taenia species [5]. In general, these assays are not yet suitable for routine diagnosis or field studies and are not widely available.

Diagnosis of taeniasis has also been made by visualizing the worm on capsule endoscopy [28].

Praziquantel is the treatment of choice for all of the tapeworm infections discussed above [41,42]. Dosing depends upon the species [43]. Dosing for taeniasis and diphyllobothriasis is 5 to 10 mg/kg orally (single dose), although excellent efficacy against T. saginata infections has been reported at doses as low as 2.5 mg/kg [44]. Dosing for hymenolepiasis is 25 mg/kgorally (single dose), followed by repeat dose 10 days later.

Praziquantel is a synthetic heterocyclic isoquinolone-pyrazine derivative that induces ultrastructural changes in the teguments of parasites, resulting in increased permeability to calcium ions. Calcium ions accumulate in the parasite cytosol, leading to muscular contractions and ultimate paralysis of adult worms [45]. By damaging the tegument membrane, praziquantel also exposes parasite antigens to host immune responses [46]. These effects lead to dislodgement of worms from their intestinal sites and subsequent expulsion by peristalsis.

Niclosamide is an acceptable alternative treatment for tapeworms if praziquantel is not available. Niclosamide comes in 500 mg tablets that need to be chewed; it is not available in the United States. Dosing consists of four tablets (500 mg) in a single dose (2 g) for adults, two tablets (1 g) for children 11 to 34 kg, and three tablets (1.5 g) for children >34 kg.

Nitazoxanide has been used to treat hymenolepiasis with 75 to 85 percent efficacy [47,48]. Dosing consists of 500 mg twice daily for three days for patients >11 years of age, 200 mg twice daily for three days for patients 4 to 11 years of age, and 100 mg twice daily for three days for patients 1 to 3 years of age [47,48].

References

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