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Cryptosporidium

This is a protozoan, obligate intracellular parasite associated with infections in humans and animals. It was first discovered in mice in 1912 and first linked with disease in man in 1976. A single species was first thought to cause disease in man but now several species have been identified. Cryptosporidium hominis is found only in humans and this together with Cryptosporidium parvum (which also infects cattle) are amongst the most common species found in man.1

Pathophysiology

Cryptosporidium oocysts when ingested are immediately infectious at quite low doses (10 to 1000 oocysts required to produce human disease). Oocysts attach to cells of the small bowel and invade the cells of the intestine. They become intracellular but extracytoplasmic and are resistant to treatment. The life cycle is completed in the host and large numbers of oocytes are then excreted with the potential to spread the infection. The oocytes are resistant to quite harsh environmental conditions and can resist chlorine levels used in water treatment.
Cryptosporidium causes diarrhoea in a number of different ways including malabsorption. Essentially all are part of the host response to infection. In normal subjects the infection is confined to small intestine but in the immunocompromised ( for example AIDS and congenital immunodeficiency) it may spread to the biliary tree.

Epidemiology

About 30% of the adult population in the USA will be seropositive. In the UK about 5-6000 cases are reported annually. Before the advent of highly active retroviral treatment 10-15% of AIDS patients developed cryptosporidiosis but the incidence has fallen as have other opportunistic infections with better treatments.
In developing countries high percentages of children are infected. In some countries studies show that as many as 90% of children under 5 are infected. Oocysts are present in stools in about 4% of stools in the USA and three to four times more frequently in developing countries. The high prevalence of AIDS in developing countries is associated with a high prevalence of cryptosporidiosis (found in as many as 50% of patients with diarrhoea).
Children with acute leukaemia seem also to be at risk from cryptosporidiosis.2
Interestingly epidemic peaks in incidence have been identified in spring and autumn coinciding with high precipitation.3 This can occur where the water supply is from underground sources of drinking water.4
Transmission is:

  • Direct from livestock (common).5
  • Personal contact (playgroups, nurseries, day centres).
  • Waterborne (water supply.6 7Swimming pool contamination). New standards relating to monitoring of water supply were introduced in 2000 in the UK.8
  • Foodborne (salads,meat products, unpasteurised dairy products and milk).9
  • From infected patients in hospital.
Presentation

The incubation period is typically 5-10 days but can be less and up to 28 days. Presentation is different in different groups:

  • Can be asymptomatic in developing countries, rarely so in developed countries
  • In healthy subjects it presents with malaise, abdominal cramps, nausea and anorexia. It progresses to sudden onset of watery, green offensive stools, occasionally with blood.
  • In immunocompromised patients the diarrhoea may be profuse almost cholera like in intensity with dehydration, malabsorption and collapse.2
  • With biliary involvement right upper quadrant pain and vomiting may be prominent (cholecystitis and other biliary and pancreatic complications).2
  • The fever is characteristically low grade and a fever over 39 degrees C should alert to other infections.

Other more protracted symptoms following infection have been reported (headaches, dizzy spells, fatigue, joint pains), more commonly with C. hominis.10

Differential Diagnosis

This includes the range of other forms of gastroenteritis including:

Investigations:
  • Stool microscopy for oocysts. Special tests and staining can be used including immunofluorescent assays, enzyme-linked immunosorbent assay (ELISA) and the most sensitive polymerase chain reaction assays (PCR).11
  • Stool culture
  • Urea and electrolytes, Liver function tests may be necessary in more protracted infection. Other tests of immune function may be required in the immunocompromised (eg CD4 counts etc).
Management

In healthy individuals the disease is self limiting and requires no treatment other than routine rehydration measures.
However in the malnourished or immunocompromised patient drugs are available:

  • Nitazoxanide shortens duration and reduces mortality in malnourished children.
  • Nitaoxanide, paromomycin and azithromycin are only partially effective and results with cryptosporidiois in AIDS patients were disappointing.
  • However antiretroviral drugs, particularly the protease inhibitors can produce dramatic improvements in clinical response. These are given in combination after the antiparasitic drugs to assist absorption of subsequent antiretroviral drugs.12,13
Complications

These can arise from biliary involvement usually in complicated immunocompromised patients. Acalculous cholecystitis may need treating with cholecystectomy. Lactose intolerance may develop and need dietary advice. Sclerosing cholangitis, pancreatitis and papillary stenosis have all been reported.2 Only very rarely have these been reported in the immune competent.

Prognosis

In healthy patients the condition is self-limiting and a full recovery is normal. With complications or in immunocompromised patients the prognosis will be determined by the nature of the complication and by the underlying condition.
Prolonged diarrhoea of more than a month and biliary disease carry a poor prognosis in AIDS.2

Prevention

This can be achieved by:

  • Boiling water to kill oocysts when contamination of water supply is notified.2
  • Special filtration or boiling of water in high risk patients.14
  • Boiling or filtration15 of water in countries with high rates of contamination and/or transmission.
  • Avoid particularly newborn animals including pets especially in the immunocompromised.
  • Health care workers and childcare workers should prevent faecal-oral spread with wearing of gloves and hand washing.

Document References
  1. Hunter PR, Thompson RC; The zoonotic transmission of Giardia and Cryptosporidium.; Int J Parasitol. 2005 Oct;35(11-12):1181-90. [abstract]
  2. Hunter PR, Nichols G; Epidemiology and clinical features of Cryptosporidium infection in immunocompromised patients.; Clin Microbiol Rev. 2002 Jan;15(1):145-54. [abstract]
  3. Naumova EN, Christodouleas J, Hunter PR, et al; Effect of precipitation on seasonal variability in cryptosporidiosis recorded by the North West England surveillance system in 1990-1999.; J Water Health. 2005 Jun;3(2):185-96. [abstract]
  4. Hunter PR; Climate change and waterborne and vector-borne disease.; J Appl Microbiol. 2003;94 Suppl:37S-46S. [abstract]
  5. Hunter PR, Hughes S, Woodhouse S, et al; Sporadic cryptosporidiosis case-control study with genotyping.; Emerg Infect Dis. 2004 Jul;10(7):1241-9. [abstract]
  6. Howe AD, Forster S, Morton S, et al; Cryptosporidium oocysts in a water supply associated with a cryptosporidiosis outbreak.; Emerg Infect Dis. 2002 Jun;8(6):619-24. [abstract]
  7. Hunter PR, Colford JM, LeChevallier MW, et al; Waterborne diseases.; Emerg Infect Dis. 2001;7(3 Suppl):544.
  8. Barrell RA, Hunter PR, Nichols G; Microbiological standards for water and their relationship to health risk.; Commun Dis Public Health. 2000 Mar;3(1):8-13. [abstract]
  9. Dawson D; Foodborne protozoan parasites.; Int J Food Microbiol. 2005 Aug 25;103(2):207-27. [abstract]
  10. Hunter PR, Hughes S, Woodhouse S, et al; Health sequelae of human cryptosporidiosis in immunocompetent patients.; Clin Infect Dis. 2004 Aug 15;39(4):504-10. Epub 2004 Aug 2. [abstract]
  11. Carey CM, Lee H, Trevors JT; Biology, persistence and detection of Cryptosporidium parvum and Cryptosporidium hominis oocyst.; Water Res. 2004 Feb;38(4):818-62. [abstract]
  12. Smith HV, Corcoran GD; New drugs and treatment for cryptosporidiosis.; Curr Opin Infect Dis. 2004 Dec;17(6):557-64. [abstract]
  13. Mofenson LM, Oleske J, Serchuck L, et al; Treating opportunistic infections among HIV-exposed and infected children: recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America.; MMWR Recomm Rep. 2004 Dec 3;53(RR-14):1-92. [abstract]
  14. Colford JM Jr, Saha SR, Wade TJ, et al; A pilot randomized, controlled trial of an in-home drinking water intervention among HIV + persons.; J Water Health. 2005 Jun;3(2):173-84. [abstract]
  15. Goh S, Reacher M, Casemore DP, et al; Sporadic cryptosporidiosis decline after membrane filtration of public water supplies, England, 1996-2002.; Emerg Infect Dis. 2005 Feb;11(2):251-9. [abstract]
Acknowledgements EMIS is grateful to Dr Richard Draper for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2007.
DocID: 939
Document Version: 24
DocRef: bgp2137
Last Updated: 19 Jul 2007
Review Date: 18 Jul 2009

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