קריפטוספורידיוזיס

What is cryptosporidiosis?¹

Cryptosporidiosis is a water- and food-borne zoonotic disease caused by the protozoon parasite of the genus Cryptosporidium. The disease can be transmitted by the faecal-oral route as well as the respiratory route. The infective stage (sporulated oocysts) is resistant to different disinfectants including chlorine.

C. hominis ו C. parvum are the main two species causing infections in humans and animals. 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.²

Cryptosporidiosis is an important cause of diarrhoeal illness worldwide, particularly in young children and immunocompromised patients.

פתופיזיולוגיה³

Cryptosporidial oocysts when ingested are immediately infectious at quite low doses (10 to 30 oocysts are 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.

קריפטוספורידיום spp. cause 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 the small intestine but in the immunocompromised (for example, AIDS and congenital immunodeficiency) it may spread to the biliary tree.

How common is cryptosporidiosis? (Epidemiology)⁴

• Cryptosporidiosis is endemic in developing countries and individuals more prone are adults with human immunodeficiency virus (HIV) infection and children.

• The prevalence of Cryptosporidium infection in underdeveloped countries such as Brazil, Venezuela, Indonesia, Thailand, South Africa, Ghana, India, and Bangladesh among children with diarrhoea varies from 3% to 13%.

• In contrast, in developed parts of the world such as Britain, United States, Canada, Australia, and Denmark, it accounts for only 1–4% of childhood diarrhoea.

גורמי סיכון

The risk factors for acquisition of cryptosporidiosis are determined by the modes of transmission. Transmission is:

• Direct from livestock (common):
  

  • Farms or petting zoos (especially in young ruminants).

  • Contact with animal dung (for example, during outdoor recreation).

• From personal contact with infected individuals (who may or may not have symptoms), eg, playgroups, nurseries and day centres.

• Waterborne:
  

  • Contaminated water supply.

  • Contamination of swimming pools and other water-based recreational sites.

  • Travel to less developed countries.

• Foodborne (unprocessed foods, notably raw milk, meat, shellfish, fresh fruit and vegetables).⁵

• From infected patients in hospital.

Symptoms of cryptosporidiosis (presentation)^{4 6}

• The incubation period is dose-dependent and typically 5-10 days. However, it can be less and also up to 28 days.

• Can be asymptomatic in developing countries; rarely so in developed countries.

• The fever is characteristically low-grade and a fever over 39°C should alert to other infections.

• In healthy subjects it presents with:⁷
  

  • Mild fever (59% of consulting patients).

  • General malaise progressing rapidly to further symptoms.

  • Sudden onset of watery diarrhoea - often green and offensive, sometimes with blood (98% of patients).

  • Abdominal cramps (95%).

  • Nausea and anorexia (65%).

  • Symptoms which are prolonged and last on average for two weeks but can persist for up to one month.

  • Relapse of symptoms, indicating persistent infection - occurs in over a third of cases.

  • Other more protracted symptoms following infection - for example, headaches, dizzy spells, fatigue, and joint pains have been reported.

  • Illness can be severe enough to necessitate admission to hospital.

Immunocompromised patients⁸

Those patients most at risk are those with:

• T-cell immune deficiency (including those with haematological malignancies - especially children).

• Patients with HIV infection and CD4 counts lower than 200 cells/mm³ (and in particular those with counts below 50 cells/mm³).

• Patients with primary T-cell deficiencies (for example, severe combined immunodeficiency).

Immunocompromised patients:

• Commonly experience more chronic symptoms.

• Have more widespread infection within the gastrointestinal tract, which may involve the pancreatic duct and gallbladder.

• Can experience more profuse diarrhoea with almost cholera-like intensity, accompanied by dehydration, malabsorption and collapse.

• Experience more complications. Biliary complications, right upper quadrant pain and vomiting may be prominent.

אבחנה מבדלת^{9 10}

This includes the range of other forms of gastroenteritis including:

• Campylobacter enteritis.

• Escherichia coli O157.

• Salmonellosis.

• Shigellosis.

• Giardiasis.

• Viral gastroenteritis.

• Amoebiasis.

See also Gastroenteritis in Adults and Older Children ו Gastroenteritis in Children.

חקירות

• Request stool microscopy for oocysts. However, routine requests may not include microscopy for קריפטוספורידיום spp. It is important to specify this request where infection is suspected. Special tests and staining can be used, including immunofluorescent assays, enzyme-linked immunosorbent assay (ELISA) and the most sensitive polymerase chain reaction (PCR) assays.²

• Stool culture.

• U&Es; LFTs may be necessary in more protracted infection.

• Other tests of immune function may be required in the immunocompromised (eg, CD4 counts, etc).

Management of cryptosporidiosis

In healthy individuals, the disease is self-limiting and requires no treatment other than routine rehydration measures.⁶

Immunocompromised patients

The aim of treatment is symptomatic improvement and clearance of the infection. Complete clearance of the parasite is unlikely without correction or improvement of the severity of the immunodeficiency and the underlying cause.

The evidence of effective treatments for cryptosporidiosis has been lacking. One large review of studies consisting of the use of nitazoxanide, paromomycin, macrolides, somatostatin analogues, letrazuril, albendazole, rifaximin, miltefosine, clofazimine, and colostrum were mostly conducted in small number of individuals infected with human immunodeficiency virus (HIV), with inadequate data of controlled trials to suggest the use of these treatment modalities.¹¹

• Nitazoxanide was reported to be highly effective only in immunocompetent hosts and was found to be superior to paromomycin in the same group of patients.

• Other trials did not show any strong evidence of benefit.

Complications of cryptosporidiosis

These are more common in immunocompromised patients - for example:

• Pancreato-biliary infection leading to pancreatitis, דלקת כיס המרה (acalculous), sclerosing cholangitis and (rarely) subsequent biliary cirrhosis. Papillary stenosis has also been reported.¹²

• Tracheo-bronchial and sinus involvement (rare).

• Pneumatosis cystoides intestinalis (cysts containing gas occur in the gut wall) occurs rarely in cryptosporidiosis with advanced HIV infection. Cysts can rupture causing pneumoretroperitoneum and pneumomediastinum.

Acalculous cholecystitis may need treating with cholecystectomy. אי סבילות ללקטוז may develop and dietary advice will be needed. Complications are unusual in the immune-competent person.

תחזית

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.¹²

Prevention of cryptosporidiosis¹

• Advice:¹³

  • Exclusions for 48 hours after first normal stool.

  • Avoid using swimming pools for two weeks after the first normal stool.

  • Normal enhanced hygiene as for any cause of gastroenteritis.

• There is no effective vaccine.

• It is recommended to move animals to clean and dry places and disinfect the contaminated areas, however, this is mostly not applicable on farms with a large number of animals.

• For humans, continuous disinfection of the contaminated areas will reduce person-to-person transmission in institutional and domestic settings.

• The infectivity of the oocyst and its survival time will be restored at low temperatures (less than 5°C) and increased by temperatures higher than 15°C for 3 months.

• Several physical stresses can affect Cryptosporidium oocysts, including irradiation, heat, cold, pressure, and desiccation.

• The most effective disinfectants against Cryptosporidium oocysts are those that contain chlorine dioxide, hydrogen peroxide, or ammonia.

• Ozone is one of the most effective chemical disinfectants against Cryptosporidium and can be used against Cryptosporidium oocysts in water.

• It has also been reported that rotifers (microscopic, aquatic invertebrates), which occupy rivers, lakes, seawater, and ponds, and predacious protozoa, can ingest oocysts of C. parvum. Some rotifers were found to discharge oocysts in boluses containing a mixture of other eaten components, and therefore they can be used for Cryptosporidium oocyst control in water.