Intestinal Protozoal Diseases Clinical Presentation
- Author: Enrique Chacon-Cruz, MD; Chief Editor: Russell W Steele, MD more...
History
The spectrum of intestinal protozoal infections can range from asymptomatic to invasive disease (in the cases of E histolytica or B coli) to severe and/or chronic and protracted diarrhea (in the cases of giardiasis or in individuals who are severely immunosuppressed with spore-forming protozoal infections).
- Amebiasis
- Noninvasive intestinal infection: Noninvasive amebiasis most frequently produces no symptoms. Nevertheless, some patients may have some ill-defined GI tract symptoms. These symptoms include alternating periods of mild diarrhea and constipation with or without mild abdominal pain; however, for the most part, patients tolerate the infection.
- Intestinal amebiasis or amebic colitis: Patients typically have 1-3 weeks of diarrhea to grossly bloody dysenteric stools with abdominal pain. Constitutional symptoms are often mild, and fever is present only in about 10-20% of cases; however, weight loss is common. Some patients manifest chronic nondysenteric diarrhea, combined with months or even years of abdominal pain associated with varying amounts of flatulence, mucus in stools, and weight loss.
- Acute fulminant or necrotizing colitis: This presentation occurs in only 0.5% of intestinal amebiasis cases and has been associated with patients inappropriately treated with corticosteroids. The patient develops sudden constipation following an acute and severe episode of dysenteric diarrhea that is followed by signs of shock.
- Ameboma: This is a mass of granulation tissue in the cecum or ascending colon, and it usually occurs in fewer than 1% of patients with intestinal amebiasis. Concurrent amebic dysentery is present in two thirds of patients. Patients usually report a tender, palpable, lower-left quadrant abdominal mass.
- Liver abscess: This occurs in 10% or fewer patients with invasive E histolytica infections. Patients usually have a history of more than 1-2 weeks of fever, abdominal pain, poor appetite, and, less commonly, cough and pleuritic chest pain. Liver abscess is associated with diarrhea only in 20% of cases. Jaundice occurs only in severe cases.
- Giardiasis
- Following excystation and colonization, a spectrum of clinical manifestations can occur. Symptomatic infections are noted more frequently in children than in adults.
- Asymptomatic excretion: The asymptomatic carrier rate of G lamblia in the United States is estimated to be 3-7% but is as high as 20% in southern regions and possibly even higher in children attending childcare centers. In endemic giardiasis, most infections produce no symptoms.
- Acute infectious diarrhea: Infections resulting from waterborne outbreaks and infections in travelers and among children in childcare centers are associated more often with significant illness. Most patients have symptoms within 10 days of exposure, and more than 90% of patients have symptoms within 3 weeks. The usual symptoms are short-lasting acute diarrhea (with or without low-grade fever), nausea, abdominal distension, greasy stools, and anorexia. Acute giardiasis may spontaneously resolve. Parasites disappear from the stools within 4-6 weeks in both experimental and naturally acquired infections; however, giardiasis can sometimes occur as intermittent diarrheal episodes and/or evolve to chronic diarrhea, anorexia, bloating, and weight loss.
- Chronic diarrhea: Chronic giardiasis is usually associated with intermittent, loose, foul-smelling stools that resemble those of malabsorption states. Abdominal distension, sulfurous belching, flatulence, epigastric pain, substernal burning, nausea, anorexia, and failure to thrive may occur. Although severe forms of chronic giardiasis may occur in otherwise healthy individuals, they are common in patients with hypoglobulinemia, particularly IgA deficiency in association with lymphoid hyperplasia of the bowel. Chronic giardiasis may contribute to protein-energy malnutrition in children. Protein-losing enteropathy has also been described. Intestinal disaccharidase deficiency associated with giardiasis can be manifested by carbohydrate intolerance, especially lactose. Evidence suggests that giardiasis may be associated with chronic urticaria, gallbladder disease, and treatment failures because of malabsorption of antibiotics during episodes of otitis media.
- Spore-forming protozoa
- Asymptomatic infections: Asymptomatic infection is part of the clinical spectrum of disease produced by these parasites. Asymptomatic infections with cryptosporidia occur in normal and immunodeficient hosts. Some data suggest that asymptomatic carriage of microsporidia in patients with AIDS may precede wasting and diarrheal illness. In one study, only 11-18% of immunocompetent Peruvian children with acute cyclosporal infections had diarrhea.[16] The reported frequency of asymptomatic infection is controversial, especially with microsporidia, Isospora, and Cyclospora. The link between infection and clinically apparent disease is strong; however, the frequency that asymptomatic infection is identified depends on the sensitivity of the assay used to detect the parasite.
- Acute infectious diarrhea in immunocompetent hosts: Acute diarrhea in immunocompetent hosts has been shown to be a predominant clinical manifestation of infection with these parasites, except for microsporidia (only one case of microsporidial diarrhea has been reported in a normal host).
- In a study developed in Austria, the correlation between detection of microsporidia in stool and GI symptoms was transient, suggesting that microsporidia infection may cause clinical symptoms during the early stages of infection that resolve even though the microsporidia persist.[17] Many studies report acute diarrhea in infants and children living in underdeveloped countries, medical personnel, travelers, and persons in institutions.
- In March 1993, the municipal water supply in Milwaukee became contaminated with cryptosporidia, and an estimated 403,000 residents developed diarrhea.[18] In normal hosts, infections by cryptosporidia, Cyclospora, and Isospora are characterized by 3-25 days of diarrhea, malaise, abdominal pain with or without nausea, vomiting, and fever. However, studies performed in the United Kingdom have shown that cryptosporidiosis can cause recurrence of gastrointestinal symptoms in as many as 40% of immunocompetent patients (more with C hominis than with C parvum), and all episodes have been self limited.[19] Giving specific treatment to immunocompetent patients with cryptosporidiosis is still not well supported.
- Disease in immunodeficient hosts
- All spore-forming protozoa have a predisposition for more frequent and prolonged infections in patients who are immunodeficient. Most reported cases are in patients with AIDS, but reports document severe cryptosporidia infections in patients with renal transplantation and persons with IgA deficiency. Isosporiasis has been reported in persons with cancer.
- The symptoms range from asymptomatic infection to severe life-threatening diarrhea, dehydration and chronic malabsorption leading to lethargy, failure to thrive, and malnutrition.
- The clinical features of 128 patients with AIDS-related cryptosporidiosis showed the following 4 patterns of disease: transient (29%), chronic (60%), fulminant (8%), and asymptomatic (4%).[20]
- As mentioned above, more severe cases of cryptosporidiosis and microsporidiosis are observed in patients with AIDS who have very low CD4 counts (< 50-100/mL). A similar spectrum of disease severity is seen in AIDS-related intestinal infection with Cyclospora and Isospora.
- HIV-wasting syndrome is a well-established clinical syndrome in patients with AIDS characterized by chronic diarrhea, chronic weakness, and/or documented fever. The physiopathogenesis of this syndrome is multifactorial, from hypermetabolism, decreased oral intake, and cytokine dysregulation, to the coparticipation of various pathogens in which spore-forming protozoa are included.
- The advent of highly active antiretroviral therapy (HAART) has decreased the frequency and severity of cryptosporidiosis in HIV infected individuals. Recovery of CD4 with HAART has resulted in resolution of chronic diarrhea in many patients.
- Extraintestinal disease: The primary location of all intestinal spore-forming protozoal infections is the small intestine, predominately the distal small bowel. Colonic infection is common with microsporidiosis. Infection in the biliary tract has been reported with cryptosporidium, Isospora, and microsporidia leading to right upper quadrant abdominal pain, occasionally with jaundice and fever. Invasion by S intestinalis beneath the epithelial surface and dissemination to the liver, respiratory tract, or the kidney has been reported. The other intestinal microsporidia E bieneusi has also been isolated from the lungs in individuals with AIDS.
- Dientamoebiasis
- Symptoms commonly associated with D fragilis infection include abdominal pain, diarrhea, anorexia, nausea, vomiting, and flatulence. Bloody stools are not observed. In a study in Belgium of 448 patients with diarrhea, D fragilis was found in 6.3%, and G lamblia was found in 7.1%.[11] Both parasites caused diarrhea and abdominal pain, but D fragilis was less frequently associated with nausea, vomiting, and weight loss.
- Less common symptoms include fever, weight loss, and fatigue.
- Diarrhea usually lasts 1-2 weeks, whereas abdominal pain can persist for 1-2 months. Because of its very high association with pinworms, some patients can also manifest anal pruritus, lower urinary tract infection (particularly young girls), or both.
- Balantidiasis
- Most infections with B coli are asymptomatic; however, some patients experience an acute or chronic illness.
- When acutely affected, the patient has diarrhea with stools containing abundant mucus and blood. Patients may also have concurrent nausea, vomiting, tenesmus, and intestinal colic, resembling an amebic colitis.
- In most patients, recovery occurs without treatment; however, in some patients, especially those who are malnourished or immunodeficient, the course can be fulminant and fatal. Usually, the course is long term with episodes of intermittent diarrhea and constipation, with or without abdominal pain, anorexia, weight loss, and weakness.
- Patients may present with an appendicitislike illness, and, in some patients, amebomalike presentations occur.
- Extraintestinal infection is rare.
- Blastocystosis
- Many experts believe that B hominis is pathogenic only when present in large numbers, but some studies have shown that the quantity of the parasite is not predictive of the presence (or severity) of the disease.
- The association of this protozoa with traveler's diarrhea and disease in the normal host is controversial. A study developed in Egypt found high concentrations of B hominis in symptomatic patients compared with asymptomatic patients, suggesting that blastocystosis may be an uncommon cause of gastroenteritis and travelers diarrhea; however, convincing information suggests that B hominis causes diarrhea in immunosuppressed patients, such as patients with renal transplants and AIDS.[21]
- The most common symptoms associated with infection include abdominal discomfort, diarrhea, flatulence, and sometimes fever and bloating. A study done in Turkey showed an association between lower anthropometric indexes and B hominis infection.[13]
Physical
- Amebic or balantidic colitis
- Most patients have nonlocalized abdominal tenderness, and one third of patients have fever (usually low-grade fever).
- Signs of dehydration are rare with these pathogens, although they can be present in young infants.
- An ameboma can be palpated on the lower right abdominal quadrant, and it is usually tender and mobile.
- Patients with acute or fulminant colitis present with severe abdominal pain, distension, and rebound tenderness, with or without fever.
- The patient may also present with signs of shock.
- In patients with amebic liver abscess, tender hepatomegaly is present in almost 100% of cases, and fever is present in 80-90% of cases, with or without hypoventilation of the lower right lung. Peritoneal signs and jaundice are unusual but, when present, are signs of severe disease.
- Giardiasis
- In children younger than 5 years, acute giardiasis can be complicated by signs of dehydration that may lead to hospitalization. However, these events are not as prominent as with other enteropathogens, such as rotavirus or enterotoxigenic bacteria.
- Signs of chronic giardiasis are more subtle. The patient may show some degree of protein-energy malnutrition, with a distended abdomen but no other pathognomonic signs.
- Spore-forming protozoa
- In immunocompetent patients, clinical findings are no different than the findings associated with giardiasis.
- Signs of dehydration are unusual but can occur.
- In immunodeficient hosts, especially patients with AIDS, diarrhea has been associated with accompanying signs of protein-energy malnutrition and even signs of hypokalemia with or without hyponatremia.
- Some patients with acute exacerbations can also manifest acute dehydration with or without metabolic acidosis.
- Dientamoebiasis and blastocystosis
- Clinical findings of dientamoebiasis and blastocystosis are no different than those found with acute giardiasis, although signs of dehydration are less frequent.
- Some immunosuppressed patients with blastocystosis may present with signs of malnutrition, but these observations can be more attributable to their underlying disease than to the parasitosis itself.
Causes
- For all intestinal protozoa, fecal-oral transmission is the primary route of transmission.
- Water and/or food contamination contributes to most, if not all, individual cases and outbreaks.
- Immunologic factors, such as IgA and T-cell responses, are important for giardiasis and spore-forming protozoa.
- Malnutrition is an important risk factor for susceptibility to all protozoa.
- Swine are, by far, the most important reservoir for balantidiasis.
- Dientamoebiasis is frequently associated with pinworm co-infection.
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| Name | Mode of Transmission | Symptoms |
| Flagellates | ||
| G lamblia | Contaminated water, fecal-oral | Nausea, bloating, gas, diarrhea, anorexia |
| Dientamoeba fragilis | Fecal-oral, associated with Enterobius | Previously thought commensal; may cause diarrhea, abdominal, pain, nausea |
| Amebas | ||
| Entamoeba histolytica | Contaminated water, fecal-oral, contaminated food | Colitis, dysentery, diarrhea, liver abscess, other extraintestinal disease |
| Spore-forming (Coccidia) | ||
| Cryptosporidium parvum | Contaminated water, swimming pools, fecal-oral | Immunocompetent patients: Self-limited diarrhea Immunosuppressed patients: Severe and interminable diarrhea |
| Isospora belli | Fecal-oral | Same as in Cryptosporidium |
| Cyclospora cayetanensis | Fecal-oral, contaminated water and food | Same as in Cryptosporidium |
| Microsporidia (Septata intestinalis, Enterocytozoon bieneusi) | Fecal-oral, contaminated water | Same as in Cryptosporidium |
| Ciliates | ||
| Balantidium coli | Fecal-oral (frequently associated with pigs) | Colitis, diarrhea |
| Other | ||
| Blastocystis hominis | Fecal-oral | May cause mild diarrhea |
| Organism | Size (mm) | Stain Used | Other Tests |
| E histolytica | Trophozoite: 10-60 Cyst: 10-20 | Wet mount,* trichrome, periodic Schiff | Enzyme-linked immunosorbent assay (ELISA) |
| G lamblia | Trophozoite: 9-21 Cyst: 7-12 | Wet mount,* trichrome, hematoxylin, Lugol | ELISA* |
| C parvum | 2-5 | Modified acid-fast,* auramine-rhodamine, Sheafer method | ELISA* |
| I belli | 30x12 | Wet mount,* modified acid-fast* | None |
| C cayetanensis | 8-10 | Modified acid-fast,* wet mount | Electron microscopy |
| Microsporidia | 1-2 | Modified trichrome* | Electron microscopy, fluorescence methods, small intestine biopsy |
| D fragilis | 7-12 | Iron hematoxylin,* trichrome* | None |
| B. coli | 50-200 | Wet mount,* concentration techniques | None |
| B hominis | 5-30 | Trichrome,* iron hematoxylin* | None |
| *Preferred screening test in clinical settings. | |||
| Organism | Drugs, Pediatric Dose, and Treatment Duration |
| E histolytica (Luminal disease or colonization) | Iodoquinol: 40 mg/kg/d PO divided tid for 20 d; not to exceed 2 g/d |
| Paromomycin: 25-30 mg/kg/d PO divided tid for 7 d | |
| E histolytica (Moderate colitis) | Metronidazole: 50 mg/kg/d PO divided tid for 10 d |
| Tinidazole: 50 mg/kg/d PO for 3 d; not to exceed 2 g/d | |
| E histolytica (Severe colitis or liver abscess) | Metronidazole: 50 mg/kg/d PO divided tid for 10 d |
| Dehydroemetine*: 1-1.5 mg/kg/d divided bid PO for 5 d | |
| Tinidazole†: 50 mg/kg/d PO for 3-5 d; not to exceed 2 g/d | |
| G lamblia | Metronidazole: 15-20 mg/kg/d PO divided tid for 5 |
| Tinidazole: 50 mg/kg/d PO once; not to exceed 2 g/dose | |
| Quinacrine‡: 6 mg/kg/d PO divided tid for 5 d; not to exceed 300 mg/d | |
| Furazolidone: 6 mg/kg/d PO divided qid for 7-10 d | |
| Paromomycin: 40 mg/kg/d PO divided tid for 7 d | |
| Nitazoxanide: 200-400 mg/d PO divided bid for 3 d | |
| D fragilis | Iodoquinol: 50 mg/kg/d PO divided tid for 20 d; not to exceed 2 g/d |
| Paromomycin: 30 mg/kg/d PO divided tid for 7 d | |
| Tetracycline: 40 mg/kg/d PO divided qid for 10 d; not to exceed 2 g/d | |
| C parvum§ | Paromomycin*: 30 mg/kg/d PO divided tid (duration unknown) |
| Nitazoxanide: 200-400 mg/d PO divided bid for 3 d | |
| I belli | Trimethoprim/sulfamethoxazole (TMP/SMZ): 20/100 mg/kg/d PO divided bid for 10 d, followed by 10/50 mg/kg/d PO divided bid for 21 d |
| C cayetanensis | TMP/SMZ: 10/50 mg/kg/d PO divided bid for 3 d |
| Microsporidia S intestinalis | Albendazole* (adult dose): 800 mg/d PO divided bid |
| Microsporidia E bieneusi | No treatment recommended; albendazole may decrease the number of organisms |
| B coli | Tetracycline: 40 mg/kg/d PO divided qid for 10 d; not to exceed 2 g/d |
| Metronidazole: 35-50 mg/kg/d PO divided tid for 5 d | |
| Iodoquinol: 40 mg/kg/d PO divided tid for 20 d | |
| B hominis | Metronidazole: 35-50 mg/kg/d PO divided tid for 10 d |
| Iodoquinol: 40 mg/kg/d PO divided tid for 20 d | |
| Nitazoxanide||: 500 mg/d PO divided bid for 3 d | |
| *Efficacy is unknown. †Drug is available from the CDC Drug Service (phone: 404-639-3670; evenings, weekends, and holidays: 404-639-2888). ‡ Drug is not available in the United States. §Recommended regimens are indicated only in patients who are immunosuppressed. A recent meta-analysis has not shown evidence for a reduction in the duration or frequency of diarrhea by nitazoxanide or paromomycin when compared with placebo in immunosuppressed patients, nevertheless, oocyst clearance was significantly reduced.[23] ||Recent studies have shown effective outcomes when compared to placebo, but no clinical trials have compared with other antiparasitic drugs. | |

