| From the Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta Georgia
Cryptosporidium parvum has been recognized as a human pathogen since 1976. From 1976 to 1982 the disease was rarely reported and primarily occurred in immunocompromised persons. In 1982, the number of reported cases began to increase dramatically as part of the AIDS epidemic. Initially the increase was limited to immunocompromised persons; however, with the aid of newly developed laboratory diagnostic techniques, outbreaks in immunocompetent persons began to be recognized. In immunocompetent persons, Cryptosporidiosis is manifested as an acute, self-limiting diarrheal illness lasting 7 to 14 days and it is often accompanied by nausea, abdominal cramps, and low-grade fever. In patients with AIDS, Cryptosporidiosis is generally chronic and more severe than in immunocompetent persons; the voluminous watery diarrhea is often debilitating and may be accompanied by severe abdominal cramps, weight loss, anorexia, malaise, and low-grade fever [1]. No safe and effective form of treatment for Cryptosporidiosis has been identified to date. On the basis of initial human treatment trials, several drugs have been reported to decrease the frequency or volume of stool production in some patients. However, to date, none of these initially "promising" drugs have lived up to expectations when subjected to larger, controlled studies or to widespread use by physicians in clinical practice. Incidence of Cryptosporidiosis Cryptosporidiosis is among the most common causes of diarrhea in patients with AIDS in the United States. About 2.2% of all patients whose cases of AIDS are reported to Centers for Disease Control and Prevention (CDC) have Cryptosporidiosis as their AIDS-defining illness; 3.5% of children whose cases of AIDS are reported to the CDC have Cryptosporidiosis. Hospital-based studies indicate that Cryptosporidiosis is diagnosed in 10%-20% of patients with AIDS who have diarrhea [2-6]. Because diarrhea occurs in about half of all patients with AIDS each year [2,7], it is estimated that the annual rate of cryptosporidial infection among all patients with AIDS may approach 5%-10%. Cryptosporidiosis can occur at any time in the course of HIV infection. However, severe and persistent disease correlates well with CD4 counts of less than 180 cellS/mm3. In one study, only 5(13%) of 39 patients infected with C. parvum and with CD4 counts of less than 180 cells/mm3 had self-limiting disease, whereas all 8 patients with CD4 counts of greater than 180 cells/mm3 had infections that cleared and did not relapse during a follow-up period of 1-24 months[8]. Source of Infection and Risk Factors Cryptosporidium species are transmitted by ingestion of oocysts excreted in the feces of infected humans or animals. Cryptosporidial infection can therefore be transmitted from person-to-person, through ingestion of fecally contaminated water or food, from animal to person, or by contact with fecally contaminated environmental surfaces. Transmission via Water and Food Six well-documented outbreaks of Cryptosporidiosis attributed to drinking water have been recognized in the United States, including an outbreak in Milwaukee in 1993 that affected over 400,000 persons [9-15]. The source of drinking water used by utilities in these outbreaks included surface water (lakes, rivers, streams), well water, and spring water. Several outbreaks have also been associated with swimming pools and amusement park wave pools or water slides [12,16-19]. There is considerable circumstantial evidence that low level (non-epidemic) transmission of Cryptosporidium species through drinking water may be occurring throughout the United States. Recent studies indicate that Cryptosporidium oocysts are present in 65% - 97% of surface waters (rivers, lakes etc.) tested throughout the country [20-23]. Because Cryptosporidium species are highly resistant to chemical disinfectants used in the treatment of drinking water, physical removal of the parasite from contaminated water by filtration is an important component of the water treatment process. However, a filtration system, especially one that is not well maintained and operated, may not afford absolute protection. All waterborne outbreaks of Cryptosporidiosis detected to date have occurred in communities where water utilities met state and federal standards for acceptable quality of drinking water, and in all three of the outbreaks that involved surface water supplies, a filtration system had been used. Data from the outbreaks suggest that compliance of utility companies with state and federal standards for water treatment may not be adequate to protect citizens from waterborne Cryptosporidiosis. Moreover, recent surveys for the occurrence of Cryptosporidium oocysts in fully treated (disinfected and filtered) municipal water demonstrate that small numbers of oocysts were able to breach filters and were present in tap water in 27%-54% of communities evaluated [23,24]. Twenty three million Americans reside in communities that do not filter municipal drinking water that comes from surface sources [25]. These communities include some of America's largest cities, which have substantial numbers of patients with HIV infections or AIDS, (e.g. New York, Boston, Seattle, Portland, and San Francisco). Small numbers of Cryptosporidium oocysts have also been intermittently found in the drinking water in these cities. However none of the cities with filtered water or with unfiltered drinking water where small numbers of oocysts have been detected have had a recognizable outbreak of Cryptosporidiosis. While low level transmission could be occurring as a result of such low concentrations of oocysts, there are no data to date that document such an event. The absence of a treatment barrier for Cryptosporidium species in communities that do not use a filtration system could result in significant transmission if the source of the drinking water were to become heavily contaminated with this organism. The health risk (especially for immunocompromised persons) associated with consumption of (filtered or unfiltered) public drinking water contaminated with small numbers of C. parvum oocysts is unknown. Although researchers are able to recover small numbers of oocysts from treated drinking water, current laboratory methods do not enable them to determine if these oocysts are viable or infectious. Moreover, it is not known if the number of oocysts present in drinking water constitutes a sufficient dose to cause illness in humans, whether immunosuppressed persons are more susceptible to lower doses of oocysts than are immunocompetent persons, or if there are strains of C. parvum that vary in infectious dose and virulence. Dose response data are currently available for only one isolate of C. parvum that was evaluated in healthy volunteers. In this study the 50% Infectous Dose was (ID50) estimated to be 132 oocysts. [26, 26a] Food contaminated with feces from infected persons or animals has always been considered to be a theoretical risk factor for Cryptosporidiosis. A recent outbreak of Cryptosporidiosis in children who drank fresh-pressed apple cider contaminated by animal feces at a county fair in Maine provides the first documentation of this mode of transmission [27]. Although oocysts do not survive cooking, infected food handlers may unwittingly transmit the infection by fecal contamination of beverages, green salads, or other foods that are not cooked or heated after handling. Animal-to-Person Transmission C. parvum is capable of infecting all species of mammals including humans [28,29]. In animals, Cryptosporidiosis almost exclusively occurs in newborns. There are no data on the national prevalence of cryptosporidial infection in puppies or kittens in the United States, but in a study in Atlanta, 10% of puppies examined at an animal shelter were found infected and shedding oocysts [30]. To date there have been no confirmed instances of C. parvum transmission from infected household pets. Two suspicious episodes have been reported in which an infected cat was found in the house of an immunodeficient person with Cryptosporidiosis; in neither instance could the direction of spread be clearly elucidated [31,32]. Other species of Cryptosporidium that infect birds (C. meleagridis and C. baileyi), rodents (C. muris), reptiles (C. serpentis), and fish (C. nasorum) are not generally considered to be infectious for humans [33]. To date, only one case of human infection with any of these species has been reported [34]; this case occured in an HIV-infected patient from whom a parasite resembling C. baileyi was isolated, but who did not not have a pet bird or other specific exposures to birds. In strong contrast to the weak epidemiological data implicating household pets as sources of Cryptosporidiosis in humans, the evidence for C. parvum transmission from calves to humans is unequivocal [35-40]. It is estimated that 50% of dairy calves shed oocysts and that the parasite is present on more than 90% of dairy farms [41-43]. While relatively few patients with AIDS are directly exposed to calves or to premises where calves are raised, the high prevalence of infected calves, especially on dairy farms, raises additional questions about the prudence of drinking unpasteurized milk. Person-to-Person Transmission Person-to-person spread of C. parvum is believed to be one of the most common modes of transmission. Children still wearing diapers who attend day care centers are at especially high risk for this form of transmission either through intimate play or because of careless diaper changing practices. Infections acquired by children in the day care setting are often transmitted to care-givers at the facility and to older children and adults who come in contact with the infected child at home [44]. Any sexual practice that brings a person into oral contact with the feces of an infected person is also considered a high-risk for exposure to Cryptosporidium species. It is not known how many patients with HIV infection or AIDS acquire Cryptosporidiosis by this route of transmission. For patients with HIV infection or AIDS who follow "safer sex" practices, including avoidance of feces, this mode of transmission should be minimal. Several other types of high-risk exposures include direct contact with feces while caring for an infected person (e. g. bathing, changing soiled bedding, or emptying a bed pan) at home or in a medical facility. Nosocomial infections involving both medical care staff and patients have been reported [45- 50]. Hospital staff should observe proper precautions for preventing fecally transmitted disease while caring for patients with Cryptosporidiosis. Prevention of Exposure The proportion of cases of Cryptosporidiosis in HIV-infected persons that can be attributed to each mode of transmission is unknown. Identification of the most common route(s) of transmission and a better understanding of the specific risk factors for exposure that lead to infection would greatly facilitate development of a more targeted prevention strategy. Until such data become available, doing what one can to avoid each of the commonly recognized modes of transmission should reduce the risk of infection. As with many other opportunistic infections for which effective treatment is not available, prevention of infection is the most effective approach to disease control. It is clear that HIV-infected persons should not drink water directly from lakes or rivers. This includes accidental ingestion of lake or river water while swimming or engaging in other types of recreational water activity. The amount of chlorine and types of filters used in public swimming pools are not adequate to prevent transmission from swimmers infected with Cryptosporidium species who can shed oocysts for weeks after symptoms resolve. Patients should be advised that these activities may expose them to Cryptosporidium species, especially if the pool is used by young children who might accidentally defecate in the pool. Because HIV-infected patients who have a cryptosporidial infection can reinfect themselves and infect others, they should not use swimming pools that will be used by others. Swimming pools can be disinfected by using high concentrations of chlorine for long periods (e.g. 3 mg/l water for 53 hours or 8 mg/l for 20 hours.) While several municipal waterborne outbreaks of Cryptosporidiosis have occurred in the US, the magnitude of risk for acquiring Cryptosporidiosis by drinking municipally treated water in the non-outbreak setting is presently unknown. The risk is likely to vary from city to city depending on the quality of the city's source of water and the quality of water treatment provided. Current risk data are not adequate to recommend that all immunocompromised persons in the U.S. boil or avoid drinking tap water. However, persons with severely weakened immune systems should be advised that the risk is not zero. Until the health risk associated with small numbers of oocysts commonly found in drinking water is more clearly defined, HIV-infected persons who want to take independent precautions to reduce the risk of waterborne Cryptosporidiosis can do so by boiling for 1 minute all water intended for drinking [51,51a]. As an alternative to boiling water, certain types of individual or household filters or a high-quality bottled water may provide nearly the same level of protection. While several portable and household filters are capable of removing Cryptosporidium oocysts from drinking water, bacterial overgrowth on these filters may pose an additional health risk [52]. Therefore, patients should be advised to carefully follow the manufacturer's instructions for the use and replacement of filters. In addition, since Cryptosporidium oocysts are likely to concentrate on the outside of a filter cartridge that has been in use, patients should have someone else change dirty cartridges or they should use gloves if they do it themselves. When selecting an effective filter one must pay careful attention to label information in order to avoid purchasing one of numerous filters on the market that are not effective against Cryptosporidium species. Only microstraining filters that can remove particles 0.1 to 1 micron in size should be considered. Filters in this category that provide the greatest assurance of removal of Cryptosporidium species include those that filter water by reverse osmosis, those that have "absolute" 1 micron filters, and those that meet NSF (National Sanitation Foundation) standard #53 for "cyst removal." The "nominal" 1 micron filter rating is not standardized and many filters in this category may not be capable of removing greater than 99% of oocysts. Filters that only employ ultra-violate light, activated carbon, or pentiodide impregnated resins are not effective against Cryptosporidium species. It should not be assumed that all filters advertised as effective against Giardia species are effective against Cryptosporidium species. Many, but not all, brands of bottled water may provide a reasonable alternative to tap water. Patients should be advised that the origin, the microbial quality, and microbial treatment of water before it is bottled vary considerably among companies and even among brands of water produced by the same company. Information on the labels of water bottles has not been standardized and often does not provide the consumer with the type of information needed to identify the product with the lowest risk for Cryptosporidiosis. As with filters, individuals who want to use bottled water as an alternative to tap water must research and pick their supplier very carefully. In general, bottled water derived from springs or wells is safer than water obtained from rivers and lakes. Bottled water that originates from well-protected underground sources (a well or a spring), that are not subject to intermittent contamination from surface water, and that have been consistently shown to be free of coliform bacteria will not contain oocysts. Since there is no industry labeling standard that reflects this information, patients may have to question vendors directly to obtain information about these points. Just as in the case of municipal water supplies, the absence of coliform bacteria in the final bottled water product does not provide assurance that the water came from an uncontaminated source or that it has been treated adequately to remove Cryptosporidium species. Treatment of water prior to bottling by distillation or reverse osmosis filtration, regardless of the source (well, spring, river, lake), assures the remove of oocysts if they are present. In addition, water that has been passaged through an "absolute" 1 micron or smaller filter, or through a filter labeled as meeting NSF standard #53 for "cyst removal" prior to bottling will provide nearly the same level of protection. Bottlers using "nominal" 1 micron filters as the only treatment barrier for Cryptosporidium species may not be capable of removing >99% of oocysts. Companies that use the word "micro-filtration" on the label may or may not be using filters that are effective against Cryptosporidium species. Although ozonation of water has also been shown to kill Cryptosporidium oocysts, the appropriate amounts of ozone needed to disinfect water at various temperatures and pHs have not been clearly defined. Bottlers are currently restricted to no more than 0.4 mg of ozone per liter in the final product. This may or may not be an adequate amount to kill Cryptosporidium species, depending on the contact time and other water conditions. In general, the amount of ozone needed to kill Cryptosporidium species is hundreds of times greater than that needed to kill bacterial contaminants [33]. Treatment of municipal tap water with charcoal to remove the chlorine taste or with short-term exposure to ultra-violet light before bottling offers no additional protection against Cryptosporidium species. The risk of Cryptosporidiosis associated with pet ownership is probably small, but it is reasonable to suggest that HIV-infected persons avoid contact with feces of animals. In situations where it is not possible to avoid such contact, e.g., cleaning a cat litter box or removing feces from shoes or other items that may have become contaminated, patients should be instructed to wear disposable gloves. The risk from household pets (dogs and cats) is greatest from exposure to animals younger than 6 months of age and to any animal with diarrhea. Physicians should inform patients that pet ownership may entail a small risk for cryptosporidial infection and should discuss how these risks can be further minimized; it should not be recommended that patients destroy or give away healthy pets with whom they have a strong emotional attachment. Immunosuppressed patients contemplating the acquisition of a new pet should avoid bringing any animal with diarrhea into their household, should avoid purchasing a dog or cat younger than 6 months of age, and should not adopt stray animals found roaming the neighborhood. HIV-infected patients who want to assume the small risk of acquiring a puppy or kitten younger than 6 months of age should be advised to specifically request that their veterinarian examine the animal's stool for Cryptosporidium species before the patient has contact with the animal. Research Priorities More rapid and sensitive serological and molecular diagnostic techniques for the detection of cryptosporidia in humans and in environmental sources are needed to facilitate epidemiologic studies of Cryptosporidiosis. High priority studies include: 1) an assessment of the proportion of cryptosporidial infections attributable to the low numbers of oocysts frequently found in municipal drinking water and 2) the relative risk of acquiring Cryptosporidiosis from drinking water versus contact with animals, unsafe sexual practices, and non-sexual household or hospital contacts. Data from such studies would serve to focus the immunocompromised patient's attention on avoidance of the exposures that would put them at greatest risk. Studies are needed to define the asymptomatic carrier rate for Cryptosporidium species in HIV-infected patients who recover from a clinical episode of Cryptosporidiosis and who have CD4 cell counts of greater than 200/mm3. There is also a need to know if such carriers are likely to develop severe Cryptosporidiosis when their CD4 count drops below 200 cells/mm3. Improved laboratory methods are needed to facilitate screening of potential therapeutic agents for infections due to Cryptosporidium species. Finally, state and national reporting systems for cases of cryptosporidial infection are needed to better quantify the public health impact of this disease and to identify outbreaks. Back to the Water Treatment Page REFERENCES 1. Petersen C. Cryptosporidiosis in patients infected with the human immunodeficiency virus. Clin Infect Dis 1992;15:903-9. 2. Weber R, Bryan RT, Thompson S, Rimland D, Kozarsky P, Juranek D. Prospective evaluation of diarrhea and enteric parasitosis in HIV/AIDS. [Abstract, 1527]. In: Program and abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy (Anaheim),Washington D.C.:American Society for Microbiology, 1992:365. 3. 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