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Cryptosporidiosis

Category: Illness or disabilities

Type

Involuntary

Introduction and description

Cryptosporidium is a genus of coccidian parasites of the phylum Apicomplexa that infects the gastrointestinal, biliary and respiratory epithelium of humans and animals.   Cryptosporidium is one of many genera of the protozoan phylum, Apicomplexa (class Sporozoea, subclass Coccidia).

During the last decade, the development of molecular typing techniques has distinguished ~20 species of Cryptosporidium and shown that C. hominis (found mainly in humans) and C. parvum (found commonly in humans and bovines) are the major species infecting humans. Occasionally, other species infect people, including

·       C. meleagridis,

·       C. felis,

·       C. canis,

·       C. andersoni,

·       C. suis,

·       C. baylei, and

·       C. muris

Cryptosporidium cause– cryptosporidiosis -  whose symptoms include watery diarrhoea (intestinal cryptosporidiosis) with or without a persistent cough (respiratory cryptosporidiosis) in both immunocompetent and immunodeficient humans.

Cryptosporidium disproportionately affects children in developing countries and immunocompromised individuals. Without a diagnostic tool amenable for use in developing countries the burden of infection and its relationship to growth faltering, malnutrition, and diarrhoeal mortality remain underappreciated.

The figures of rates of infection world-wide seem to vary a great deal - cryptosporidiosis “ may account for 1%-10% of diarrheal disease worldwide”. [PMID: 11819481]  However there is now recognition that its prevalence and effects may be considerably under reported:

Cryptosporidium is ….. one of the most common human enteropathogens worldwide, with young children living in developing countries and persons with HIV/AIDS experiencing more frequent and more severe illness sometimes complicated by malnutrition and long term impairment of physical fitness. Reported cases in industrialized countries are also rising due to the leading role that Cryptosporidium plays as a cause of waterborne outbreaks. However, the true global burden of cryptosporidiosis is not known, owing at least in part to the lack of simple, inexpensive diagnostic tools, underappreciation of the frequency and severity of disease in immunocompetent patients, and difficulties quantifying the impact of an infection that causes an acute illness with long term sequelae.  PMID: 22907279

Symptoms

Cryptosporidiosis is typically an acute, short-term infection, but it can be recurrent through reinfection in immunocompetent hosts, and become severe or life-threatening in immunocompromised individuals.   A subset of the immunocompromised population is people with AIDS and there have been deaths associated with this pathogen in this group.

We describe two patients with HIV/AIDS who presented pulmonary and intestinal infection caused by Cryptosporidium parvum, with a fatal outcome. PMID: 27007564

C. parvum normally displays a clear predilection to infect only certain sites within the host. The parasite usually infects epithelia in the intestine, respiratory tract and bile ducts - the biliary tree and gall bladder epithelium. In the human intestine, the stomach is rarely infected, and the upper small bowel, colon, and rectum are less affected than the mid small bowel.

BUT, in immunocompromised people, the pathogen appears to go all over the body

Cryptosporidium baileyi were found in the stool of an immunodeficient patient. In autopsy material, cryptosporidia were found in the esophagus, whole intestine, trachea, larynx, lungs, and gall and urinary bladders. PMID: 1825238

Acute

Cryptosporidiosis is typically an acute, short-term infection, with two main types of symptoms.

  • Intestinal cryptosporidiosis – The most common clinical manifestation of cryptosporidiosis is diarrhoea, characteristically profuse and watery and often containing mucus but rarely blood or leucocytes. Other clinical signs observed include abdominal cramps, low grade fever, nausea and vomiting. The duration and severity of clinical symptoms depend largely on the immune status of the infected individual. In immunocompetent individuals, the disease is usually self-limited. After an incubation period of 7-10 days, > 90% of infected cases present with watery diarrhoea lasting approximately 2 weeks, 50% present with nausea, vomiting and cramp-like abdominal pain and 36% present with a febrile illness. In immunocompromised individuals, the disease is much more severe.
  • Respiratory cryptosporidiosis  - respiratory cryptosporidiosis may occur commonly in immunocompetent children with cryptosporidial diarrhoea and unexplained cough. Findings from animal models, human case reports, and a few epidemiological studies suggest that Cryptosporidium may be transmitted via respiratory secretions..
    Upper respiratory cryptosporidiosis may cause inflammation of the nasal mucosa, sinuses, larynx, and trachea, accompanied by nasal discharge and voice change. Cryptosporidiosis of the lower respiratory tract typically results in productive cough, dyspnea, fever, and hypoxemia.
    While fecal-oral transmission is indisputably the major route of infection, transmission via coughing and fomites is also possible in situations of close contact ….. respiratory cryptosporidiosis may occur commonly in immunocompetent individuals.

Chronic

Chronic symptoms appear to be caused when the person’s immune system is compromised by stress, or the natural protective flora of the intestine is damaged by pharmaceuticals – especially antiobiotics and immunosuppressants, although antiemetics and anti-diarrhoeals appear also [ironically] to play a role.  Once the integrity of the intestine has been compromised,  dysbiosis occurs and the parasite is able to enter the blood stream.  From there a host of illnesses can result including:

Gall bladder disease

Gall bladder cysts, growths, tumours and cancers have been found to be associated with parasites, especially, but not exclusively in the immunocompromised, including the Cryptosporidium species.

We report a case of an immunocompetent child who developed gallbladder hydrops during a concurrent diarrheal illness caused by Cryptosporidium parvum. PMID:  11740331

Crohn’s disease and IBD

In a number of papers the similarity of Crohn’s disease and Cryptosporidiosis has been noted

Cryptosporidiosis may present with acute findings initially mimicking Crohn's disease.  PMID: 9286220

But there is also the possibility that Cryptosporidiosis is one overlooked cause of Crohn’s disease

Other organs

One extremely worrying finding of the following research is that there may be effects on organs which have not actually been infected directly

…. By using 10--14-day rats as a model, the authors have … evidence that even 4-day intestinal cryptosporidiosis may trigger obvious negative changes … in organs where the parasite does not develop. In the infected rats, growth retardation was registered, in addition to liver hypertrophy and partial heart atrophy.  ….. leading eventually to long-term consequences in further life of formerly infected individuals.  PMID:  16562739

Cryptosporidium species in more detail

Cryptosporidium is capable of completing its lifecycle within a single host, resulting in cyst stages that are excreted in faeces or through coughing fomites and are capable of transmission to a new host.  It is worthy of note that other apicomplexan pathogens include the malaria parasite Plasmodium and the toxoplasmosis parasite Toxoplasma, both of which cause extremely serious diseases.    Several intrinsic properties of this parasite help to explain its epidemiologic behavior.

  • Firstly, oocysts are infectious immediately upon being excreted in faeces, are shed in high numbers (up to 109 per stool), and can be passed for as long as 2 months after cessation of diarrhoea
  •  Secondly, the infectious dose is low, with as few as 9–10 oocysts of certain C. parvum and C. hominis strains producing symptoms
  • Third, oocysts can remain infectious in the environment for at least 6 months if kept moist, resist disinfection (including chlorination), and survive in properly chlorinated recreational water venues for >10 days
  • Fourth, the protracted incubation period (average 7 days, range 1–30 days) allows transmission to continue for days before an outbreak is recognized by public health authorities.
  • Finally, age-related decreases in disease incidence suggest that immunity induced by prior exposure is protective; thus, those lacking protective immunity (e.g., children in endemic settings and immunocompromised persons) are most at risk.

With this in mind, one can appreciate how Cryptosporidium spreads proficiently in settings without adequate sanitation and hygiene in both developed and developing countries.

C. parvum has a monoxenous life cycle, all stages of development (asexual and sexual) occurring in one host. The entire life cycle may be completed in as few as 2 days in many hosts, and infections may be short-lived or may persist for months.
Once ingested, oocysts excyst in the gastrointestinal tract releasing infective sporozoites. The freed sporozoites attach to epithelial cells and become enclosed within parasitophorous vacuoles, developing attachment organelles (stages referred as trophozoites). The trophozoites then undergo asexual proliferation by merogony and form two types of meronts. Type I meronts form 8 merozoites that are liberated from the parasitophorous vacuole when mature; the merozoites then invade other epithelial cells where they undergo another cycle of type I merogony or develop into type II meronts.
Type II meronts form 4 merozoites which do not undergo further merogony but produce sexual reproductive stages (called gamonts). Sexual reproduction occurs by gametogony and both microgamets (male) and macrogametocytes (female) are formed. Macrogametocytes are then fertilized by mature microgamets, and the resultant zygotes undergo further asexual development (sporogony) and form sporulated oocysts containing 4 sporozoites. Most oocysts are thick-walled and are excreted from the host in faecal material; some oocysts, however, are thin walled and have been reported to excyst within the same host leading to a new cycle of development. The presence of these auto-infective oocysts and recycling type I meronts are believed to be the means by which persistent chronic infections may develop in hosts without further exposure to exogenous oocysts PMID: 11819481

Causes

Water

While most cases of transmission involve oocysts derived from faecal samples, contaminated water is a source of infection among international travelers, and outbreaks have been associated with contamination of well water, surface water, swimming pools and public water supplies. C. parvum oocysts have been recovered from untreated surface waters, filtered swimming pool water, and most importantly, from treated drinking water.

A good example of its remarkable transmissibility is a statewide outbreak in the United States during May to December 2007 which involved 5,697 cases and ~450 contaminated recreational water venues. As the outbreak propagated, secondary transmission from ill contacts became increasingly important, eventually outweighing recreational water exposure as a risk factor

Many commercial disinfectants (based on aldehyde, ammonia, alcohol, chlorine or alkaline compounds) are ineffective when used according to the manufacturers’ instructions and most conventional methods of water treatment do not effectively remove or kill all the oocysts from contaminated water.

Exposure to animals

Cryptosporidium is transmitted primarily by the fecal-oral route either by direct contact with an infected human or animal or indirectly via contaminated food or water. Contamination of crops, other agricultural products, and surface water with faeces from cattle and other livestock is another important mechanism of zoonotic transmission.

Extra-intestinal infections by Cryptosporidium parvum have been detected in pigs and sheep. ….In addition to intestinal infections, cryptosporidial oocysts were found in the gall-bladders of two pigs which were 2 months old, and in some organs of sheep aged 5 days or more, including the gall-bladder , mesenteric lymph nodes , trachea , lung and the uterus of a lamb.  PMID:  8533278

Nutritional deprivation

The presence of these parasites can both cause nutritional deprivation, but be caused by it.  Zinc deficiency

Paneth cells are important contributors to the intestinal antimicrobial barrier through synthesis and release of antimicrobial peptides and proteins. Animal studies indicate that Paneth cell numbers, location and granule morphology are altered by infection and zinc status.  PMID:  14738460

Contaminated food

Like many faecal-oral pathogens, Cryptosporidium can also be transmitted by contaminated food.

Anal sex

Amongst MSM with AIDS, insertive anal sex is an increased risk factor.  Analingus and oral-genital sex after anal-genital sex are known transmission routes.

Laboratory exposure

Other transmission routes include exposure to laboratory specimens. Monkeys used in animal experiments have developed this disease

Treatment

Address the causes

Prevention

Water treatment - Many treatment plants that take raw water from rivers, lakes, and reservoirs for public drinking water production use conventional filtration technologies. Direct filtration, which is typically used to treat water with low particulate levels, includes coagulation and filtration but not sedimentation. Other common filtration processes including slow sand filters, diatomaceous earth filters, and membranes will remove 99% of Cryptosporidium. Membranes and bag- and cartridge-filter products remove Cryptosporidium specifically.

For the end consumer of drinking water believed to be contaminated by Cryptosporidium, the safest option is to boil all water used for drinking.

Ultraviolet light treatment  - at relatively low doses will inactivate Cryptosporidium

Animal welfare – the evidence shows that animals housed in large open barns or kept in fields under more humane conditions either do not develop this disease or quickly recover from it. 

Exclusive breastfeeding - during the first 3 months of life, and partial breast feeding (compared to no breastfeeding) thereafter, appears to afford some protection.  Rather intriguingly this applies to animals other than humans as well.  Research done on calves showed that the humoral immunity of the calf did not prevent infection with Cryptosporidium, but the severity of the diarrhoea symptoms decreased with increasing total IgG concentrations.

Avoidance of immunosuppressants – as we have seen above, the use of immunosuppressants has resulted in the pathogen infecting organs throughout the body.  There is also an indication, that the increased use of immunosuppressants ,as well as the rise in AIDS, has caused far more cases to be reported in the immunocompetent, as the pathogen has spread via the immunosuppressed

Prior to late 1982, only 11 cases of human infection had been reported, with the first human case reported in 1976. During the 1980s, the number of human cases began to rise dramatically. Most of these patients were immunodeficient, many of whom had the acquired immune deficiency syndrome (AIDS). ….. Immunocompromised patients develop severe, irreversible diarrhoea, often thought to be a significant contributing factor leading to death. PMID:  2481458

Diagnosis

One of the largest challenges in identifying outbreaks is the ability to verify the results in a laboratory. At present, most cryptosporidial infections are diagnosed by the microscopic examination of host faecal material for the presence of C. parvum oocysts. Experimental studies have shown that oocyst excretion coincides well with the onset and duration of most clinical signs of disease. Most asymptomatic individuals can be screened to detect subclinical infections and even water samples can be examined for contamination by oocysts. C. parvum oocysts are much smaller than those of other coccidian parasites, and they differ in many of their staining and buoyancy characteristics. Thus, most conventional coprological techniques used in parasitology and microbiology laboratories are not entirely suitable for their detection. Many specialized staining procedures have been described to stain the oocysts and differential staining techniques are more desirable to avoid confusion. The technique of choice for many diagnostic laboratories has been acid-fast staining.

Treatment

 of gastrointestinal infection in humans involves fluid rehydration, electrolyte replacement, and management of any pain. “Replacement of fluids and electrolytes is the critically important first step in the management of cryptosporidiosis, particularly in patients with large diarrheal losses. Fluids should include sodium, potassium, bicarbonate, and glucose. “

Warmth is essential to help the immune system, as is sleeping and rest.

Supplemental zinc may improve symptoms,  particularly in recurrent or persistent infections or in others at risk for zinc deficiency.

References and further reading

  • Sponseller JK, Griffiths JK, Tzipori S (July 2014). "The evolution of respiratory Cryptosporidiosis: evidence for transmission by inhalation". Clinical Microbiology Reviews. 27 (3): 575–86. doi:10.1128/CMR.00115-13. PMC 4135895. PMID 24982322.
  • Cabada MM, White AC, Venugopalan P, Sureshbabu J (18 August 2015). Bronze MS, ed. "Cryptosporidiosis Treatment & Management". Medscape. WebMD. Retrieved 8 January 2016.
  • Chlorine Disinfection of Recreational Water for Cryptosporidium parvum. CDC. Retrieved 2007-05-06.
  • Korich DG, Mead JR, Madore MS, Sinclair NA, Sterling CR (May 1990). Effects of ozone, chlorine dioxide, chlorine, and monochloramine on Cryptosporidium parvum oocyst viability. Applied and Environmental Microbiology. 56 (5): 1423–8. PMC 184422. PMID 2339894.
  • Rochelle PA, Fallar D, Marshall MM, Montelone BA, Upton SJ, Woods K (2004). Irreversible UV inactivation of Cryptosporidium spp. despite the presence of UV repair genes". The Journal of Eukaryotic Microbiology. 51 (5): 553–62. doi:10.1111/j.1550-7408.2004.tb00291.x. PMID 15537090.
  • Borchardt KA, Noble MA (25 June 1997). Sexually Transmitted Diseases: Epidemiology, Pathology, Diagnosis, and Treatment. CRC Press. p. 192. ISBN 978-0-8493-9476-8.
  • World J Gastroenterol. 1999 Oct 15; 5(5): 424–429. Published online 1999 Oct 15. doi:  [10.3748/wjg.v5.i5.424]  PMCID: PMC4688613  PMID: 11819481  Human intestinal and biliary cryptosporidiosis  Xian-Ming Chen and Nicholas F. LaRusso
  • Curr Opin Infect Dis. 2012 Oct; 25(5): 555–563. doi:  [10.1097/QCO.0b013e328357e569]  PMCID: PMC4465599  NIHMSID: NIHMS654379  PMID: 22907279  Burden of disease from Cryptosporidiosis  Debbie-Ann T. Shirley, MD, Shannon N. Moonah, MD, ScM, and Karen L. Kotloff, MD
  • Schweiz Arch Tierheilkd. 2016 May;158(5):341-50. doi: 10.17236/sat00062.  [Clinical epidemiology of cryptosporidiosis in calves]. [Article in German; Abstract available in German from the publisher]  Weber SE1, Lippuner C1,2, Corti S3, Deplazes P2, Hässig M1.  PMID:  27518579  DOI:  10.17236/sat00062
  • Parasitol Res. 1991;77(1):44-7.  The first finding of Cryptosporidium baileyi in man.  Ditrich O1, Palkovic L, Stĕrba J, Prokopic J, Loudová J, Giboda M.
  • J Comp Pathol. 1991 Nov;105(4):415-21.  Chronic pancreatitis and biliary fibrosis associated with cryptosporidiosis in simian AIDS.  Baskerville A1, Ramsay AD, Millward-Sadler GH, Cook RW, Cranage MP, Greenaway PJ.  PMID:  1770178
  • Vet Pathol. 1972 Nov;9(6):426-440. doi: 10.1177/030098587200900603.  Cryptosporidiosis in Two Juvenile Rhesus Monkeys.  Kovatch RM1, White JD1.  PMID:  29883995
  • J Ultrasound Med. 2004 Jan;23(1):137-40. Gallbladder cryptosporidiosis in a patient with acquired immunodeficiency syndrome: sonographic evaluation of the disease's course.  Megremis S1, Segkos N, Daskalaki M, Tzortzakakis E, Paspatis G, Zois E, Sfakianaki E.  PMID:14756363
  • Vet Parasitol. 1995 Oct;59(3-4):201-5.  Detection of Cryptosporidium oocysts in extra-intestinal tissues of sheep and pigs.  Fleta J1, Sánchez-Acedo C, Clavel A, Quílez J.
  • Pediatr Infect Dis J. 2001 Dec;20(12):1179-81.  Diarrhea and gallbladder hydrops in an immunocompetent child with Cryptosporidium infection.  Westrope C1, Acharya A.
  • An Pediatr (Barc). 2012 Feb;76(2):111-2. doi: 10.1016/j.anpedi.2011.09.004. Epub 2011 Oct 26. [Hydrops gallbladder due to cryptosporidium in an immunocompetent patient]. [Article in Spanish] Flores MI, Esquitino MA, Martínez AR, Reguera YM, García EM, Neth O.  PMID: 22032886
  • Med Parazitol (Mosk). 2006 Jan-Mar;(1):3-7.  [Intestinal cryptosporidiosis at an early age and its negative consequences].  [Article in Russian]  Beĭer TV, Sidorenko NV, Anatskaia OV.

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