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Giardia and Cryptosporidium: Parasites Have Long Lives Even Without Hosts

Isaacs, Lawrence MD

ID Rounds

Dr. Isaacs is a clinical assistant professor of emergency medicine at the Temple University School of Medicine, an emergency physician at Lourdes Hospital of Burlington County in Willingboro, NJ, and the medical director of the Willingboro Ambulance Service, Endeavor.

Both organisms are infectious by ingestion, and are commonly contracted by hikers and campers

Giardia and Cryptosporidium have specific implications in immunocompetent patients, in immunocompromised patients, and in infants and children. Both parasites can live outside a host's body for a long time, are infectious by ingesting the organism, and are found throughout the United States. Anyone who hikes and camps should be aware of the risks of contracting these parasites and the methods of preventing illness.

Giardiasis is the disease caused by infection with Giardia lamblia (or Giardia intestinalis, the name some feel is correct), a single-celled parasite that lives in the intestine of animals and humans. The cystic form is responsible for transmission; it is hardy, and can survive for months in cold water. It is the most common intestinal parasite in North America.

Infection occurs when the individual ingests the cysts (as few as 10 to 25) by drinking contaminated water or food, or by the fecal-oral route. In North America, the fecal-oral route accounts for a very substantial number of cases; people with poor hygiene (children in day care, male homosexuals, and institutionalized adults) are at risk. In the small intestine, the cyst opens to release two organisms (trophozoites), which may remain in the proximal small intestine (using a ventral sucking disk) or migrate distally to the colon. In the colon, it reincapsulates, forming a cyst and exiting in feces.

Symptoms begin approximately seven to 14 days after infection, and usually last seven to 21 days. The predominant symptoms are diarrhea, abdominal pain, and bloating. Some patients also complain of nausea, vomiting, and sulfuric smelling belches. Many patients will have weight loss greater than 10 pounds, and moderate to severe dehydration is a concern in pregnant women and children under age 5.

In untreated chronic Giardiasis, there may be periods of constipation. Approximately 20 percent of those infected with Giardia cysts will be asymptomatic. Interestingly, there are mechanisms for partial host immunity, and in mice, CD4 cells seem to play an important role in clearing infection. In addition to intrinsic immunity, both human and animal breast milk contain anti-Giardia antibodies and several studies1–3 have shown decreased rates of infection in breastfed versus bottlefed children. Patients with HIV do not seem to have more severe disease, but they do have an impaired immune response to the parasite.4

The disease should be considered in any patient with prolonged diarrhea, especially patients in high-risk groups such as children in day care, homosexual men, or campers returning from endemic areas. The diagnosis is confirmed by microscopic examination of the stool for cysts or trophozoites. One important limitation to this test is a false negative result early in the disease. This is a result of a longer time to passage of cysts than onset of symptoms.

It also is important to realize that the stool exam is most frequently heme negative and without white blood cells. There also are several commercially available stool antigen studies (either ELISA or immunofluorescence), all of which have sensitivities approaching 98%. Although not usually necessary, a sampling of duodenal contents (via string test, duodenal biopsy, or aspiration) is another diagnostic option. In the string test, bile-stained duodenal mucus is examined for trophozoites. This is usually reserved for cases in which there is a high level of suspicion despite negative stool examinations. Finally, there is a serum assay for anti-Giardia antibodies, although generally this is reserved for epidemiological studies.

Symptoms of Giardiasis last seven to 21 days, and include diarrhea, abdominal pain, and bloating

The treatment for Giardiasis, although it never received FDA approval, is metronidazole. The recommended dose is 250 mg TID for five to seven days. For children, the dose of metronidazole is 15mg/kg/day divided TID for five to seven days. The FDA approved furazolidone for treatment, and it comes in a liquid form (useful for children), but it is less effective than metronidazole. When faced with a pregnant patient with this infection, the drug of choice is paromomycin, which is an oral aminoglycoside.5 Another option in pregnant patients is using metronidazole in the second or third trimesters.6 There are two drugs, quinacrine and tindazole, not available in the United States that also treat Giardiasis.

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Ingestion of Oocysts

Cryptosporidium is an intracellular protozoan parasite first described in 1907 in mice, but as the 20th century progressed, it was found to cause disease in animals and humans. By the 1980s and the outbreak of AIDS, it became recognized as an important cause of diarrhea in immunocompetent and immunosuppressed humans. It was responsible for infecting more than 400,000 people in the Milwaukee area in 1993.

Infection begins by ingestion of oocysts, which begin the infectious cycle after exposure to bile salts and digestive enzymes. After several stages of maturation, some organisms divide and reinfect the host, while others leave in the stool as infectious oocysts. Outside the host, the oocysts can live for many months at moderate temperatures, and require heating to 72 degrees C for one minute to be inactivated. Immunological studies in the 1990s worldwide have shown a significant number of individuals to be positive for anti-Cryptosporidium IgG, IgM, or IgA, with rates varying between 20 percent and 60 to 70 percent.7 It is a very important cause of diarrhea in HIV-infected patients, with about two to three percent of all HIV-positive patients and 20 to 30 percent of all HIV-positive patients with diarrhea excreting cysts.8

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Causes of Infection

Infection is caused by the ingestion of cysts, either by drinking contaminated water, swimming pools, contact with infected items (diapers or toys), or hand-to-mouth. Day care workers, children in day care, animal handlers, and institutionalized persons are all high-risk individuals. Even domesticated animals are reservoirs, but their role in infection is yet to be determined. Transmission from contaminated food also has been reported.

The oocysts have a thick outer wall that resists chemicals, and is too small for many water filters, which makes decontamination difficult but not impossible. The symptom of infection is primarily diarrhea, but Cryptosporidium also can infect the respiratory or hepatobiliary systems, causing symptoms related to the organ system infected. It also has been known to cause hepatitis, pancreatitis, and arthritis. After a seven- to 10-day incubation period, diarrhea, low-grade fever, nausea, vomiting, and in some but not all patients crampy abdominal pain become the primary complaints.

The description of the diarrhea is variable, from scant and intermittent to watery and voluminous. It may contain mucus, but rarely has blood or leukocytes. Cholycystitis may affect as many as 10 percent of HIV patients with Cryptosporidium infection. The symptoms and liver function studies will be consistent with cholycystitis, and ultrasound will show a thickened gall bladder wall and dilated ducts but no gallstones. The primary pulmonary symptom is cough, but hoarseness, wheezing, and a croup-like illness all have been reported.

Most immunocompetent patients will recover spontaneously within a few weeks, but immunocompromised patients have difficulty clearing the organism. Most HIV-positive patients with a CD-4 count above 200 cells/mm3 will eventually clear the infection, but most with low CD-4 counts will not, and the diarrhea often contributes to the patient's morbidity and mortality.

The diagnosis is generally made by direct microscopic visualization of oocysts from a fecal specimen. There also are ELISA and immunofluorescent diagnostic studies commercially available. There is no proven treatment for Cryptosporidium, and the mainstay of treatment is supportive care and anti-motility agents. Hospitalization is sometimes required, usually for dehydration. Specific treatment using antimicrobials has not been very successful. Pyrimethamine, metronidazole, and the anti-plasmodium antibiotics (chloroquine, mefloquine, quinine) all have been studied without success. Clarithromycin and azithromycin also have been studied, but results at this point are generally inconclusive. Nitazoxanide has some promising results in immunocompetent patients. For HIV-infected patients, anti-retroviral therapy to raise their CD-4 counts is probably the most effective treatment today.5

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Preventing Infection

Some discussion on prevention of Giardiasis and Cryptosporidium infection is important. Because fecal-oral transmission is a major route for both of these organisms, good hygiene, including hand washing, avoiding animal feces, and using gloves when appropriate all help prevent infection. For campers and hikers who drink water from lakes and streams, there are two safe ways to remove these organisms for safe drinking.

The first way would be to boil the water for at least one minute, and secondly, to use commercially available personal filters, but the filter must be rated as capable of filtering 1 um particles or less. The use of chlorinating or iodinating tablets inconsistently kills Giardia and does not kill Cryptosporidium, so their use is not recommended. Remember that uncooked foods that may have been washed with untreated water also should be avoided.

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References:

1. Nayak N, Ganguly NK, Walia BNS, et al. Specific secretory IgA in the milk of Giardia Lamblia-infected and uninfected women. J Infect Dis 1986;155:724.
2. Morrow AL, Reves RR, West MS, et al. Protection against infection with Giardia lamblia by breast feeding in a cohort of Mexican infants. J Pediatr 1992;121:363.
3. Walterspiel JN, Morrow AL, Guerrero ML, et al. Secretory anti-Giardia lamblia antibodies in human milk: Protective effect against diarrhea. Pediatrics 1994;93:28.
4. Janoff EN, Smith PD, Blaser MJ. Acute antibody responses to Giardia lamblia are depressed in patients with AIDS. J Infect Dis 1988;157:798.
5. The Medical Letter on Drugs and Therapeutics. Drugs for parasitic infections. April 2002.
6. Mandel G, Bennett J, Dolin R. Mandel Douglas and Bennett's Principles and Practice of Infectious Disease. 5th ed. Churchill Livingstone. Philadelphia. Electronic pages: 2891.
7. Kuhls T, Mosier D, Crawford Department, et al. Seroprevalence of cryptosporidial antibodies during infancy, childhood and adolescence. Clin Infect Dis 1994;18:731.
8. Mandel G, Bennett J, Dolin R. Mandel Douglas and Bennett's Principles and Practice of Infectious Disease. 5th ed. Churchill Livingstone. Philadelphia. Electronic pages: 2904.
© 2003 Lippincott Williams & Wilkins, Inc.