Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Enteric Parasites
Enteric parasites are important agents of disease throughout the world. Although the frequency and severity of parasitic diseases are most extreme in the developing world, changes in worldwide travel, immigration, commerce, day care for young children, and increasing numbers of immunocompromised patients have led to a rising incidence of parasitic diseases in the developed world. Parasitic disease may mimic other gastrointestinal (GI) disorders, such as inflammatory bowel disease, hepatitis, sclerosing cholangitis, peptic ulcer disease, and celiac disease. Parasitic infection can also trigger overt manifestations of quiescent chronic intestinal disorders.
Epidemiology
A variety of epidemiologic factors predispose patients to parasitic infestation worldwide, but the single most important factor is socioeconomic status. It has been shown repeatedly, in both the developed and developing world, that children of lower socioeconomic status have higher parasite loads and a greater prevalence of multiple infestations. , Travel to developing countries can expose an individual to parasites that may not cause symptoms until weeks, months, or years later. Immigrants from developing countries often harbor pathogens that are unfamiliar to physicians in the immigrants’ new homelands, where these pathogens may be passed on to new neighbors. Less obvious sources of parasites include the foodstuffs that are increasingly imported from all areas of the world. The United States has experienced outbreaks of intestinal cyclosporiasis from imported fresh raspberries, romaine lettuce, and cilantro. Giardia , Cryptosporidium , and Cyclospora have been identified in packaged salad greens imported to Canada from the United States.
Protozoan infections endemic to the developed world, such as giardiasis, are transmitted with great efficiency in day-care centers, where fecal-oral contamination is common. Institutions for the developmentally disabled are also common reservoirs for Giardia, Entamoeba histolytica , and other protozoans. Pets and livestock are potential sources of Cryptosporidium, Giardia , and Toxocara species, canine hookworm, Balantidium coli , and other organisms.
Dietary habits can also be risk factors. Consumption of raw or undercooked fish can lead to Diphyllobothrium latum, Capillaria philippinensis , or Anisakis infection. Inadequate cooking of pork predisposes to Taenia solium and Trichinella infections. Raw or undercooked beef can harbor Taenia saginata . Furthermore, a variety of protozoan organisms can be transmitted via produce that has been exposed to human or animal waste. Unpasteurized apple juice has been reported as a cause of Cryptosporidium outbreaks.
Host Factors
Children, particularly toddlers, are more susceptible to these infestations, owing to their habit of mouthing environmental objects, their propensity to go barefoot, and their immunologic “naivete.” Patients with compromised immune systems—whether due to congenital defects, infections such as human immunodeficiency virus (HIV), or medical ministrations (transplant and oncology patients)—may have severe, protracted, or unusual manifestations of parasitic disease. Patients with hypogammaglobulinemia and immunoglobulin A (IgA) deficiency may have severe protozoan infections such as giardiasis. Patients with acquired immunodeficiency syndrome (AIDS) who are infected with Cryptosporidium organisms may have severe, prolonged diarrhea as well as unusual manifestations in the biliary tree and lungs despite high levels of luminal IgA antibody directed against Cryptosporidium . Sexual practices, particularly those that involve anal penetration, are also associated with the transmission of parasitic diseases. ,
Clinical Presentations
Enteric parasites most often produce GI symptoms—abdominal pain, diarrhea, flatulence, and distension. In a children’s hospital laboratory survey testing for stool ova and parasites, it was found that stools sent from the gastroenterology clinic were most likely to be positive as compared with stools submitted from other outpatient clinics, the emergency room, or inpatient settings. Heavy infestations of large worms such as Ascaris can lead to intestinal obstruction or, if they migrate into the biliary system, biliary obstruction with cholangitis or pancreatitis. Amoeba and Trichuris organisms can cause enterocolitis with tenesmus and mucoid, bloody stool.
Liver disease from enteric parasites can result from bile duct obstruction by organisms such as Ascaris worms or liver flukes or from portal hypertension caused by inflammatory reactions to ova, as in schistosomiasis. Some protozoans, such as Cryptosporidium , can infect biliary epithelium and produce syndromes such as cholangitis and cholecystitis. Other protozoans, such as E. histolytica , can cause hepatic parenchymal necrosis resulting in liver abscesses.
Systemic manifestations of parasitic infestation are also common. Loss of intestinal luminal blood and protein can lead to anemia and edema. Fever is often the most prominent feature of amebic liver abscess. Malabsorption is common in giardiasis and cryptosporidiosis and can lead to wasting, deficiency of fat-soluble vitamins, and failure to thrive. Onset of nephrotic syndrome has been associated with Giardia lamblia, Strongyloides stercoralis, and possibly hookworm species.
Diagnosis
Stool Examination
Traditionally the mainstay of diagnosing enteric parasites is a skilled microscopist in the parasitology laboratory. Because the skills of microscopists vary, clinicians are advised to select reference laboratories with care. Meticulous attention to the appropriate collection, preservation, and examination of samples is critical to the successful diagnosis of enteric parasites. Furthermore, the observation of fecal leukocytes, eosinophils, and macrophages in preserved specimens may provide clues to parasitic GI diseases.
Appropriate sample collection begins with ascertaining that no interfering substances that could invalidate the results are present in the stool. Common interfering substances include barium (from contrast radiography), bismuth preparations, antacids, and mineral oil. Antibiotics can also make the detection of protozoans difficult. It is preferable to wait 2 weeks after the ingestion of any of these substances before obtaining a specimen. Clinicians evaluating GI symptoms should obtain stool specimens before initiating GI radiology studies and certain forms of empiric therapy. Water and urine contamination of stool lead to rapid lysis of trophozoites and should be avoided.
Although examination of a fresh stool specimen is useful for identification of motile trophozoites, it is rarely performed in laboratories in the United States. Most stools are collected in preservatives, which allows for convenience in both collection and examination. The commonly used preservatives, such as formalin and poly(vinyl) alcohol, are toxic if ingested.
The appropriate number and frequency of stool examinations remains controversial. It is clear that repeated samples obtained on separate days enhance sensitivity by at least 20%, owing to variable shedding of eggs, cysts, and trophozoites. For patients with low clinical-epidemiologic risk factors in areas of low prevalence of parasitic infection, such as in the United States, one sample may be adequate, providing a sensitivity of about 70% and a negative predictive value greater than 90%. However, when there is a high index of suspicion for infection, at least three samples may be needed, particularly for E. histolytica, Strongyloides, and Dientamoeba fragilis .
Some enteric parasites, most notably Cryptosporidium and Cyclospora species, are not detected on routine ova-and-parasite examinations. These organisms require either acid-fast staining or special immunofluorescence techniques.
Polymerase Chain Reaction
The development of a commercially available GI pathogen panel (GI PCR) that simultaneously tests for 22 different enteric viral, bacterial, and parasite pathogens in a single stool specimen has revolutionized the way in which the etiologic diagnosis of intestinal gastroenteritis is made in the developing world. With respect to parasites, this rapid test can detect Cryptosporidium species (although it cannot differentiate among the 23 species), Cyclospora cayetanensis , E. histolytica , and G. lamblia with a sensitivity and specificity greater than 99% (excluding E. histolytica , whose prevalence was too low to be calculated in the study). Compared with conventional stool culture and molecular methods, the GI PCR has a rapid turnaround time, as fast as 1 hour; a wide selection of pathogens tested; and excellent sensitivity and specificity.
Immunoassay
Enzyme-linked immunosorbent assays (ELISAs) for antigen in stool samples are widely available for Giardia and Cryptosporidium species. These sensitive and specific assays can be useful adjuncts to standard stool examinations. Because several common organisms can cause the clinical picture of giardiasis, ELISA is not recommended as the sole means of evaluating patients except in the context of a known outbreak. ELISA for Strongyloides has a sensitivity of up to 95% and specificity of 90%.
Macroscopic Examination
Ascaris lumbricoides worms can be passed intact in the stool or vomited, particularly during febrile illness. They are easily recognized because of their size (15 to 40 cm) and resemblance to earthworms. Cestodes, or more commonly, segments of cestodes, can also be passed per rectum. Species identification is possible by microscopic examination. Enterobius organisms venture nocturnally onto the perianal area to lay eggs. The small thread-like worms may be visualized, or the “Scotch tape” test may be employed to identify the eggs of this common parasite.
Serology
Serologic detection of antibodies to E. histolytica is possible in 85% of patients with dysentery and 95% of infected patients who have liver abscesses in nonendemic areas. Specific serology for Giardia and Strongyloides may be useful in some cases.
Eosinophilia
Eosinophils are granulocytes with cytoplasm that stains strongly with acid dyes such as eosin. They normally make up less than 5% of circulating granulocytes, or an absolute count of fewer than 500/mm 3 . Elevation of eosinophils in the peripheral blood is associated with allergy, connective tissue disease, infections, and malignancy. Only invasive parasitic infections are associated with a peripheral eosinophilia, and the degree of elevation is proportional to the degree of invasion. Protozoal infections rarely cause eosinophilia. Circulating eosinophils are a marker of much higher tissue aggregations of eosinophils, usually in the skin and epithelial tissues. Eosinophil production is stimulated by cytokines released by Th2 cells. The Th2 immune response is triggered by allergens and helminths and differs from the Th1 response involved in bacterial and viral infections. Eosinophilia is not a sensitive screening tool for parasitic infection. However, if eosinophilia is present, infection with Ascaris , hookworm, visceral or cutaneous larva migrans, Strongyloides, Trichinella, Trichuris, Cystoisospora, Enterobius, C. philippinensis, or tapeworm must be considered.
Intestinal Fluid and Biopsy
Duodenal fluid may be useful in the diagnosis of giardiasis or strongyloidiasis when stool specimens are negative. Fluid may be obtained by duodenal intubation or during endoscopy; it should be examined immediately. The Entero-Test is a gelatin capsule containing a string that adsorbs duodenal fluid. It is swallowed and then retrieved by a string taped to the patient’s cheek. This technique may be difficult to perform in young children.
In selected patients, duodenal biopsy may reveal Giardia, Cryptosporidium, microsporidia, or Strongyloides organisms. Biopsy of the edges of colon ulcers may reveal trophozoites of E. histolytica . The sensitivity of intestinal biopsy for the diagnosis of parasitic disease depends to a large degree on the interest and experience of the pathologist.
Benefits of Parasites
Interest is growing in a hypothesized link between lack of exposure to helminthic infection and the development of allergy. Several studies have shown that children with chronic parasitic infections have reduced skin reactivity to common environmental allergens, such as the house dust mite, as compared with noninfected children with otherwise similar exposures. , There seems to be benefit both from current parasite infection and from repetitive infection in infancy. Inflammation triggers CD4 + T-cell production of either a Th1- or Th2-predominant response. Th1 cytokines stimulated by bacterial and viral infections are the cytokines that mediate a normal inflammatory response. Th2 cytokines are stimulated by parasites and allergens and cause an allergic response, but the response is modified and IgE degranulation is inhibited in the case of parasitic infections. Recurrent exposure to parasites in infancy is thought to downregulate the Th2 response and lessen the likelihood of induction of allergy. Current parasite infection also downregulates the inflammatory response, possibly to allow the parasite to mature and reproduce. The role of the antiinflammatory cytokines such as interleukin 10 (IL-10) is important because repetitive parasitic and other infections upregulate IL-10 and ensure a normal termination of inflammation.
As with allergy, the incidence of inflammatory bowel disease is said to be inversely related to the prevalence of parasitic infection. Immune tolerance and autoimmunity, mediated by Th3/Tr1 cells, also depends on the balance of antiinflammatory cytokines IL-10 and transforming growth factor β (TGF-β) with pro-inflammatory cytokines from the Th1 pathway. Parasitic infections downregulate Th1 responses implicated in the mucosal inflammation seen in inflammatory bowel disease. Literature to date is limited regarding the efficacy of helminths being used to induce remission in inflammatory bowel disease.
Medication Difficulty
In the past decade, generic medications that treat parasite infections have become outrageously expensive. Because these infections are less common in the United States, there is little to no financial incentive for multiple drug companies to produce these generic drugs, thereby allowing one company to have a monopoly and increase prices. For example, 400 mg of albendazole in the United States can cost up to $400, whereas in the United Kingdom it is about $2 and in Tanzania 4 cents. Similar occurrences have been seen with praziquantel and pyrimethamine. ,
Pathogenic Organisms
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here