Etiologic agent = Cryptosporidium parvum

This coccidian protozoan is an extremely important emerging pathogen in humans. While it induces only a self-limiting, acute diarrheal disease in immunocompetent individuals, it is a leading cause of life-threatening, chronic diarrheal disease in immunocompromised patients. 10% of AIDS patients are infected and cryptosporidiosis is a leading cause of mortality among AIDS patients.

Life cycle of Cryptosporidium parvum:

Infection occurs by ingestion of oocysts excreted in the feces of animals or other humans. These oocysts contain 4 sporozoites that initiate infection of the gastrointestinal tract following ingestion and excystation. The organism replicates both asexually by schizogony and ultimately sexually to produce new oocysts that are shed into the environment in the feces.

Several points regarding Cryptosporidium ecology are important:

• The organism is highly infectious.
  • The median infective dose (from human trials!) is only 132 oocysts, and 20% of human subjects could be infected with as few as 30 oocysts!
• The oocysts are highly resistant to inactivation in the environment.
  • There is no chemical method of inactivation to kill the organism in drinking water.
• There is no routinely successful form of therapy for use in vivo.
  • Paromycin has been investigated in cats with persistent diarrhea and in human patients. However, the use of paromycin in cats has been associated with the development of acute renal failure, deafness and cataract formation when the drug is absorbed across damaged intestinal epithelium.

What is the role of animals in the epidemiology of infection in humans?:

Person-to-person transmission of Cryptosporidium parvum is extremely important, and numerous outbreaks have been documented in childcare and other institutional settings. In addition, there appear to be genotypes of the organism (genotype 1) that are resticted to humans. However, animals are clearly a major source of genotype 2 Cryptosporidium parvum.

Dogs and cats:

Cryptosporidium organisms have been isolated from the feces of dogs and cats. Infections appear to most commonly be subclinical, but may induce mild diarrhea. Cryptosporidium isolates from HIV patients have been specifically matched to isolates from dogs and cats (see Pieniazek et al., 1999) and it is now considered that there is a dog-specific genotype (C. canis) and a distinct feline genotype (C. felis), both of which can be infectious for humans. However, there are also studies showing no statistical association between human infections and dog or cat ownership.

Cattle:

The domestic animal of most importance as a reservoir of Cryptosporidium parvum is clearly cattle.

• Neonatal calves are infected during the first days of life, leading to diarrheal disease.
• Nationally, in a study of 7,369 calves on 1,103 farms, oocysts were detected in the feces of calves on 59.1% of farms and from 22.4% of all calves tested. In a second study by Atwill et al., 92% of calves 7-21 days of age were shedding the organism in their feces. In a third study, rates of shedding among calves were lower, ranging from 0-13%, but the odds ratio for shedding was still higher for calves 2-4 months of age than in older cattle.
  • Interestingly, the incidence of cryptosporidiosis in people in the U.K. dropped substantially during the foot and mouth disease outbreak in 2001!

Clearly cattle may serve as a major source for environmental contamination with Cryptosporidium parvum. But is Cryptosporidium parvum DIRECTLY zoonotic from cattle to humans?:

• Infection has been well-documented among students and staff in veterinary school settings, suggesting direct infection from hospitalized animals.
• On a broader scale, among people in WI, one study found that 44% of farmers vs. 24% of non-farming neighbors were seropositive.
  • However, another study found a 60% seropositivity rate among the general population.

Other animals:

• Studies have found high rates of seropositivity among horses, but few instances of clinical disease.
  • Infection is particularly associated with diarrhea in SCID (severe combined immunodeficient) Arabian foals.
• Pigs can be naturally and experimentally infected, but seldom show clinical signs.
• Llamas and alpacas can shed C. parvum.
• Cryptosporidium parvum has been isolated from subclinically infected guinea pigs.
• Birds and reptiles can also harbor Cryptosporidium spp. and suffer either gastrointestinal (often primarily manifest as regurgitation in reptiles) or respiratory disease, but with the exception of C. meleagridis from birds, these strains are rarely zoonotic.
• Deer have recently been shown to harbor a genotype of C. parvum that is infectious for humans.
• Mice are infected with a gastric Cryptosporidium species (C. muris) that can infect people, especially HIV patients.

Water as a source of Cryptosporidium parvum infection for humans:

Surface water:

• Cryptosporidium parvum has been found in 65-97% of rivers, lakes and other surface water sources tested in the U.S.

Municipal water supplies:

• The largest outbreak in history was the waterborne outbreak in Milwaukee, WI in the spring of 1993, with 403,000+ cases. A similar, but smaller scale, outbreak occurred in the U.K. in 1999 after infected sheep contaminated a reservoir in England that supplied the cities of Manchester and Lancashire.
• Additional municipal waterborne outbreaks have occurred, and in all cases the treatment plants met state and federal guidelines for treatment procedures.
• Outbreaks have also been associated with public swimming pools.
  • The bottom line is that current water treatment guidelines (e.g. chlorination levels, etc.) were largely designed to eradicate coliforms, and Cryptosporidium parvum is not sensitive to chlorination.
  • Filtration is the key and new approaches/guidelines are needed, as are ways of determining whether organisms found in water are still viable and infectious.

Foodborne cryptosporidiosis:

• A recent outbreak in Minnesota was due to contamination of chicken salad.
  • The hostess operated a child care in her home and had changed diapers before preparing the salad.
• Another outbreak occurred following a fair in Maine in 1993. Kids went into an apple orchard and picked up fallen apples from which they made apple cider.
  • Unfortunately, the orchard was also used as a cattle pasture.
  • This apple cider was the vehicle for 160 primary cases of cryptosporidiosis among the fair-goers, with 53 secondary human-to-human cases.
  • The organism was isolated from each step along the way in the cider making process, beginning with cow manure in the pasture.
• Infection has also been documented to be due to inadequately pasteurized milk provided to a school.

Can we eradicate Cryptosporidium parvum as a public health concern by eradicating the organism on dairy farms...and can we even reasonably expect to do that?:

At the present time, the answer is NO for the following reasons:

• It is clear that we cannot vaccinate calves to protect them, since they are infected too early in life for active immunization to be effective.
  • One approach that's being pursued is to generate immunity in the dams, that can then be passively transferred to calves. But it remains unclear what type of immunity is needed for protection and whether this can be achieved through vaccination of the dams.
• Person-to-person spread remains a major factor in transmission and there appear to be genotypes of C. parvum that are specific for humans, in addition to the zoonotic genotypes.
• Studies of specific manure handling practices are needed to determine if alternative methods can reduce environmental contamination by the organism until other approaches can be implemented to reduce the rate of infection among cattle.
• Finally, what is urgently needed for both cattle and humans is an antiprotozoal agent that can kill the organism.

Diagnosis of Cryptosporidium parvum infection:

• detection of the organism in fecal floatations, acid-fast staining of the organism in fecal smears or immunofluorescent antibody labeling of organisms in fecal smears

Treatment:of Cryptosporidium parvum infection:

• There is no effective chemotherapeutic agent for the routine treatment of cryptosporidiosis!
  • Paromycin has been investigated in both cats and human patients, but it is not used widely and demonstration of its efficacy in other species is still lacking. In addition, the use of paromycin in cats has been associated with the development of acute renal failure, deafness and cataract formation when the drug is absorbed across damaged intestinal epithelium.
  • Nitazoxanide has demonstrated efficacy in cell culture, animal models, and some human patients.
    • Azithromycin also shows some promise.

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