• Users Online: 302
  • Print this page
  • Email this page

Table of Contents
Year : 2022  |  Volume : 16  |  Issue : 5  |  Page : 34-40

Cryptosporidium infection in solid organ transplant recipients in South Asia - Expert group opinion for diagnosis and management

1 Department of Nephrology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Nephrology and Renal Transplant Medicine, Medanta Kidney and Urology Institute, Medanta Medicity, Gurugram, Haryana, India
3 Consultant Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Sindh, Pakistan

Date of Submission01-Sep-2021
Date of Acceptance21-Feb-2022
Date of Web Publication18-Oct-2022

Correspondence Address:
Dr. Narayan Prasad
Department of Nephrology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute Medical Sciences, Lucknow, Uttar Pradesh
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijot.ijot_80_21

Rights and Permissions

Cryptosporidium is a protozoan ubiquitous in natural water sources worldwide. It is a common intestinal pathogen that frequently causes gastroenteritis syndrome. It is mainly transmitted from person to person via the fecal-oral route, sexual transmission, and possibly through respiratory secretions. After an incubation period of a few days to 2 weeks, it presents as an asymptomatic oocyst passer to clinically evident profuse and prolonged diarrhea, associated with nausea, vomiting, abdominal pain, and fever. The extraintestinal manifestations may occur in the form of respiratory tract disease, pancreatitis, cholangitis, rarely sclerosing cholangitis, and urinary tract infection. Stool microscopy examination for identifying oocysts is the mainstay diagnostic tool. The association with cancer is new evolving paradigm with cryptosporidium infection. Nitazoxanide is the treatment of choice. However, paromomycin in combination with other antiparasitic agents, such as macrolides (azithromycin, spiramycin), and nitazoxanide may be a more effective option in case of no response.

Keywords: Cryptosporidium, diarrheal illness, nitazoxanide, solid organ transplantation

How to cite this article:
Prasad N, Bansal SB, Akhtar SF. Cryptosporidium infection in solid organ transplant recipients in South Asia - Expert group opinion for diagnosis and management. Indian J Transplant 2022;16, Suppl S1:34-40

How to cite this URL:
Prasad N, Bansal SB, Akhtar SF. Cryptosporidium infection in solid organ transplant recipients in South Asia - Expert group opinion for diagnosis and management. Indian J Transplant [serial online] 2022 [cited 2023 Feb 2];16, Suppl S1:34-40. Available from: https://www.ijtonline.in/text.asp?2022/16/5/34/358665

  Introduction Top

Cryptosporidium, an intracellular parasitic protozoan, is a common intestinal pathogen that frequently causes gastroenteritis syndrome.[1],[2] It is ubiquitous in natural water sources throughout the world and is acquired through contaminated food or water, leading to diarrheal illness.[3],[4],[5]

  Epidemiology Top

The exact prevalence and incidence, although unknown, vary according to socioeconomic status in both developed and developing countries. Cryptosporidiosis in solid organ transplant (SOT) recipients is a relatively uncommon illness in the USA and Europe and reported either as case reports or small series.[6],[7],[8],[9],[10] A few case series and epidemiological studies of stool carriage of Cryptosporidium in SOT recipients are reported from endemic areas of the Middle East, India, and South America.[11],[12],[13],[14],[15],[16],[17],[18],[19] However, the prevalence among diarrheal patients is reportedly as high as 12% in developing countries.[20] We observed that cryptosporidiosis accounts for most infectious diarrhea (28.5%) in adult transplant recipients.[21] A Brazilian study[14] reported cryptococcal infection in 35% renal transplant (RT) recipients as compared to 17% in the control population. In comparison, a Turkish study[22] showed 21% in RT recipients than 3% in immunocompetent patients. In pediatric SOT recipients, Cryptosporidium infections account for 18% of infectious diarrhea cases over 3 years and 3.5% in the new recipients.[23] The data reveal that children and immunosuppressed patients are disproportionately affected by cryptosporidium infection.[20]

  Transmission and Pathogenesis of Cryptosporidium Top

The life cycle of cryptosporidium is shown in [Figure 1]. Cryptosporidium is transmitted from person to person mainly via the fecal-oral route, sexual transmission, and possibly through respiratory secretions.[24],[25],[26],[27],[28],[29],[30] Outbreaks of cryptosporidiosis have been described in daycare canters,[31],[32] in association with animal petting farms,[33],[34] and contaminated drinking as well as recreational water use.[35],[36] Children, residents, and travelers to endemic areas and intestinal graft recipients carry a higher risk of cryptosporidium infection.[11],[14],[37],[38],[39]
Figure 1: Life cycles of cryptosporidium in brief. The Sporulated oocysts are excreted by the infected host mainly through faeces (step 1) and the cysts are used as diagnostic material as well. Transmission of Cryptosporidium spp. occurs mainly through ingestion of fecally contaminated water, food or following direct contact with infected animals or people or possibly sometimes through inhalation (step 2); and following ingestion by a host, excystation occurs (step-3), leading to infection. Finally, the sporozoites are released and infect the epithelial cells. The thick wall oocyst are excreted and thin walled oocyst cause autoinfection (the figure has been adopted from https://www.cdc.gov/dpdx/cryptosporidiosis/index.html

Click here to view

Infectivity depends on the number of oocysts and species and subtypes of cryptosporidium.[40],[41] Cryptosporidium parvum (C. parvum) and Cryptosporidium hominis (C. hominis) account for >90% of the human cases.[28],[42],[43] The parasite binds to the apical surface of the intestinal epithelium and promotes its reproduction. All the life stages of cryptosporidium are observed in the microvillus border of epithelial cells and within the bronchial mucus glands in case of respiratory tract infection.[44]

It inflicts direct injury to the epithelial cells and produces a local inflammatory response by activating the immune system and the release of pro-inflammatory cytokines. It leads to impairment of the absorption and secretory function of the intestine.[1],[45]

Toll-like receptors (TLR2 and TLR4) present on intestinal epithelial cells play an important part in initiating immune activation following mucosal injury by the parasite.[46],[47],[48] The activation of TLRs leads to cytokine release (IL-12, IL-15, IL-18, TNF-α, and IFN-α/β), followed by recruitment of other cells of the innate immune response such as NK cells, macrophages, and dendritic cells. The production of I IFN-γ and IL-8 by these cells, is responsible for further activation of the innate and adaptive immune systems. The effect of these leads to crypt cell hyperplasia, villous atrophy, and blunting and killing of infected cells.[49],[50],[51]

The role of the T-cell function and IFN-γ is supported by severe and prolonged cryptosporidiosis in patients with acquired immunodeficiency syndrome (AIDS) and CD4 count <50 cells/mm3, and improvement of the symptoms after the introduction of highly active antiretroviral therapy.[52],[53],[54]

  Clinical Features Top

The incubation period of cryptosporidium ranges from a few days to 2 weeks. The clinical presentation may vary from asymptomatic oocyst passers to clinically evident profuse and prolonged diarrhea, associated with nausea, vomiting, abdominal pain, and fever.[1],[12],[22],[53],[54],[55],[56],[57],[58],[59] It may manifest with other nonspecific symptoms such as generalized weakness, myalgia, anorexia, and headache.[1],[3],[5],[60] Persistently irregular bowel can lead to dehydration and wasting, leading to increased morbidity.[23],[55],[60] Dehydration, hypotension, and sometimes tacrolimus toxicity may lead to acute kidney injury.[7],[8],[9],[16],[22],[55],[60],[61],[62],[63],[64] [Box 1].

  Extraintestinal Manifestations Top

The extraintestinal atypical manifestations may occur in the form of respiratory tract disease,[28],[65],[66],[67],[68] pancreatitis, cholangitis, rarely sclerosing cholangitis,[2],[57],[59],[61],[69],[70],[71],[72] and urinary tract infection.[73] It is usually observed in immunocompromised SOT patients and AIDS patients.[71],[72],[73],[74]

Respiratory cryptosporidiosis may present with upper or lower respiratory tract involvement. It manifests with nasal discharge, voice change, cough, dyspnea, and hypoxemia.[65],[66],[67],[68] Infection of the biliary tree could act like an extraintestinal reservoir. It may be responsible for relapses if not treated with drugs that have biliary excretion.[2],[75] Relapse rates in cryptosporidiosis are high (up to 40%–60%) due to incomplete eradication of the oocysts, especially from the biliary tree, possibly due to inadequate intestinal drug levels in patients with severe diarrhea.[57],[58] The cryptosporidiosis illness is typically self-limited in immunocompetent hosts and may have protracted courses in immunocompromised patients in AIDS patients, transplant recipients on immunosuppression, and hypogammaglobulinemia.[7],[25],[37],[55],[59],[62],[73]

  Diagnosis Top

Stool microscopy examination for identifying oocysts is the mainstay diagnostic tool for cryptosporidium infection.[75],[76],[77],[78],[79],[80] However, it has low sensitivity if the concentration of oocysts is low. The size of oocysts (usually 3–7 μm) may be misdiagnosed as a yeast infection. Modified staining with Ziehl–Neelsen or fluorescent techniques such as auramine-rhodamine improves the detection.[75],[76]

Direct immunofluorescence is now a commonly used method. The enzyme-linked immunosorbent assay kits are available with sensitivities ranging from 66% to 100% with excellent specificity.[29],[77],[78],[79],[80] Immunochromatographic tests are rapid but have lower sensitivity for species other than C. parvum or C. hominins.[81],[82]

Multiplex polymerase chain reaction test that can detect different gastrointestinal pathogens, including viruses, parasites, and bacteria, are now available in many laboratories, including ours.[83],[84] It has high sensitivity and carries a high cost.[40],[41],[60],[85]

Intestinal biopsy and tissue histopathology is a useful method for diagnosis if indicated.

Parasites are seen within the lumen or on lining epithelial surfaces. It is particularly crucial for intestine transplant recipients when diarrhea persists, despite negative stool examination.[7],[86],[87] Sputum and other respiratory samples may also be examined with the same methods in the scenario of respiratory infections.[65],[66],[67]

  Treatment Top

The stepwise treatment approach is shown in [Figure 2].
Figure 2: Stepwise approach and treatment of cryptosporidium infection

Click here to view

  General Management Top

Oral or intravenous rehydration depending on the severity of dehydration is the mainstay of management. A lactose-free diet may be preferred as cryptosporidium may destroy mature epithelial cells lining the villi resulting in loss of enzymes such as lactase. Antimotility agents should only be used if other causes of diarrhea such as Clostridium difficile or dysentery are ruled-out.

  Modulation of Immunosuppression Top

The next step of management in SOT recipients is optimizing immunosuppression as severity is linked with the degree of immunosuppression.[12],[21],[22],[25],[87],[88] The reduction of immunosuppression may result in the clearance of parasites.[59]

Mycophenolate may induce diarrhea. However, it carries some antiparasitic activity against cryptosporidium by inhibiting folate metabolism.[55] Cryptosporidium induced diarrhea may also result in increased tacrolimus toxicity. It occurs because of a combination of factors, including reduced cytochrome 3A activity during inflammation,[25],[89] reduced P-glycoprotein activity of intestinal cells and increased absorption, and possible interaction with other drugs that may result in acute kidney injury as well.[4],[5],[25],[37],[55],[89]

In the cases of nonresponsiveness, partial response to the antimicrobials, relapse, or in the presence of other opportunistic infections, we suggest reducing the degree of overall immunosuppression and to switch mycophenolate to Azathioprine, and in case of concomitant tacrolimus toxicity, switching tacrolimus to cyclosporine may be considered.[21]

  Antiparasitic Agents Top

The stepwise protocol for the approach and treatment is shown in [Figure 1]. Antiparasitic drugs such as nitazoxanide, paromomycin, or azithromycin are commonly used drugs. However, nitazoxanide is an approved drug for treating cryptosporidiosis by the FDA; yet, it has no significant drug-drug interactions. It does not require dose adjustments in renal or hepatic failure.[90] Nitazoxanide has been effective in 3 randomized clinical trials among immunocompetent adults and children, showing a reduction in diarrhea duration and eradication of cysts from stool.[91],[92] Its effectiveness in immunocompromised patients has been variable, with some clinical trials showing positive results, whereas, in other trials, the drug was no better than placebo. The recommended nitazoxanide dose in SOT recipients is 500 mg twice daily for 14 days;[25] however, data from randomized trials in SOT recipients is lacking, and longer therapy courses are sometimes employed.[3],[4],[8]

Paromomycin, a nonabsorbable aminoglycoside, has limited activity against the parasite, and it requires a higher concentration to inhibit parasitic activity.[93] Paromomycin in combination with other antiparasitic agents such as azithromycin and Nitazoxanide may be a more effective option.[7],[11],[13],[14],[16],[22],[37],[56],[58],[62],[63],[94]

Macrolide antibiotics such as azithromycin, clarithromycin, or spiramycin also have activity against cryptosporidium.[90] It reduces the duration of symptoms and oocyst shedding in a clinical trial of treating children with cryptosporidiosis.[95],[96] However, these findings were not consistent in the subsequent randomized trial.[96] Successful use of spiramycin and azithromycin alone or in combination therapy with paromomycin or nitazoxanide in SOT patients has been described.[7],[13],[37],[56],[58],[63]

Several clinical trials and case series studied the use of azithromycin in immunocompetent and immunocompromised patients with cancer and HIV infection. However, it showed mixed results in clinical response, including duration of symptoms and oocyst shedding.[97],[98],[99],[100] Drug interaction of macrolides with tacrolimus or cyclosporine must be considered before prolonged use of macrolides.

Rifabutin is also effective against Cryptosporidium.[101] However, the drug interaction resulting in a reduced level of tacrolimus and cyclosporine again raises a concern on using this drug in organ recipients. Rifaximin has also been shown to be active in vitro. Although Tacrolimus levels are not affected by rifaximin, the elevation of rifaximin levels may occur because of P-glycoprotein inhibition.

Because individual drugs lack full activity against the parasite, the use of combination therapy may be a more attractive option. Current guidelines recommend starting with nitazoxanide alone as preferred therapy, although combination therapy is an alternative option.[25] In our own study, we observed a higher response rate (85.7% vs. 38.46%), stool clearances (95% vs. 61.5%), and a lower relapse rate (9.5% vs. 15.3%) of combination therapy of Nitazoxide plus fluoroquinolones compared to nitazoxanide alone.[21]

If the biliary tract is the reservoir of infection in immunocompromised patients, then paromomycin-like medicines should be avoided. This drug is not absorbed and may lead to relapses. Drugs with biliary excretion, such as nitazoxanide, should be preferred in these patients.[2],[70] Relapse rates in cryptosporidiosis are high (up to 40%–60%) due to the Incomplete eradication of the oocysts, especially from the biliary tree, and possibly due to inadequate intestinal drug levels in patients with severe diarrhea.[57],[58] Acalculous cholecystitis may require cholecystectomy. Sclerosing cholangitis may need endoscopic retrograde pancreatography with possible papillotomy and stenting, along with antiparasitic drugs.[94]

  Prevention Top

SOT recipients should avoid drinking untreated wells, streams, and lake water. Cryptosporidium oocysts are resistant to chlorine disinfection and survive for days in treated recreational water despite adequate chlorination.[24],[102] SOT recipients should avoid swimming in unclean streams or lakes. Although no pieces of evidence are available, particular precautions will be required if recipients move to an endemic zone of infection.

Drinking water should either municipal treated properly, filtered by <1 μm filters, or bottled water. SOT recipients should avoid contacting patients with diarrhea. Handwashing is strongly encouraged for everyone, including other family members. Contaminated surfaces should be cleaned with running water and soap.[25],[103]

  Future Perspectives Top

Passive immunity enhancement

Hyperimmune colostrum (oral bovine immunoglobulin [IgG]) and monoclonal or polyclonal antibodies may reduce oocyst excretion and clinical symptoms.[104],[105] However, they sometimes may increase diarrhea. These agents with antiparasitic agents may be a strategy to consider in refractory immunocompromised individuals.[105] The decline in infection rate with age indicates the acquisition of immunity[29],[52] against the parasite, although such a protective immune response is not well studied.[29],[68] Rechallenge of infection in healthy volunteers showed that after the second re-challenge, diarrhea episodes were similar, but clinical severity was milder and fewer subjects were shedding oocysts.[106] Both IgG and immunoglobulins A antibodies increased after exposure; however, there was no correlation with infection.[106]

Newer antiparasitic agents

In-depth studies of genomes of C. parvum and C. hominis open the pathways of the invention of many newer antiparasitic drugs. They are targeted against calcium-dependent protein kinases, hexokinase, lactate dehydrogenase, and inosine-5-monophosphate dehydrogenase. A few fatty acyl-CoA binding inhibitors and microtubule formation inhibitors are also being studied. It may be a therapeutic agent against this infection in the future.[87],[107]

Vaccine development

Vaccine prevention remains a goal of any infection, producing morbidity and mortality. A vaccine was investigated in a mouse model.[108] There are several challenges of vaccine development for cryptosporidium, particularly in clinical practice.[109] The two most common species causing human disease, C. parvum, and C. hominis, share >95% of their genome, so it may be possible to have one vaccine for both species. Several parasitic antigens such as gp15 and gp40 have been evaluated in vaccine development. Both elicit an immune response and production of interferon-gamma by mononuclear cells in patients previously infected with cryptosporidium. A vaccine trial in Bangladesh using IgA against gp15 showed the antibody was not species-specific and resulted in a shorter illness duration.[87]

A recombinant DNA vaccine using Vaccinia, Salmonella, or Lactobacillus as DNA vectors has also been under investigation.[87] However, the efficacy of these vaccines still needs to be proven first in immunocompetent and subsequently in immunocompromised individuals.

Association with cancer

There are emerging controversies about cryptosporidium as the cause and consequences of cancer. Nevertheless, a meta-analysis recently reported a positive association between Cryptosporidium infection and cancer in general and colorectal cancer in particular.[110],[111] Immunocompromised people may have a higher risk of developing malignancy induced by this parasite, especially if immunosuppression is more severe.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Bouzid M, Hunter PR, Chalmers RM, Tyler KM. Cryptosporidium pathogenicity and virulence. Clin Microbiol Rev 2013;26:115-34.  Back to cited text no. 1
Chalmers RM, Davies AP. Minireview: Clinical cryptosporidiosis. Exp Parasitol 2010;124:138-46.  Back to cited text no. 2
Chen XM, Keithly JS, Paya CV, LaRusso NF. Cryptosporidiosis. N Engl J Med 2002;346:1723-31.  Back to cited text no. 3
Guerrant RL. Cryptosporidiosis: An emerging, highly infectious threat. Emerg Infect Dis 1997;3:51-7.  Back to cited text no. 4
Ok UZ, Cirit M, Uner A, Ok E, Akçiçek F, Başçi A, et al. Cryptosporidiosis and blastocystosis in renal transplant recipients. Nephron. 1997;75:171-4.  Back to cited text no. 5
Burdese M, Veglio V, Consiglio V, Soragna G, Mezza E, Bergamo D, et al. A dance teacher with kidney-pancreas transplant and diarrhoea: What is the cause? Nephrol Dial Transplant 2005;20:1759-61.  Back to cited text no. 6
Delis SG, Tector J, Kato T, Mittal N, Weppler D, Levi D, et al. Diagnosis and treatment of cryptosporidium infection in intestinal transplant recipients. Transplant Proc 2002;34:951-2.  Back to cited text no. 7
Franco A, Rocamora N, Merino E, Paya A. Cryptosporidiosis. A rare infection in renal transplantation. Nefrologia 2006;26:753-4.  Back to cited text no. 8
Gasink LB, Seymour C, Blumberg EA, Goldberg LR, Fishman NO. An uncommon presentation of an uncommon disease: Leprosy in a heart transplant recipient. J Heart Lung Transplant 2006;25:854-6.  Back to cited text no. 9
Scallan E, Hoekstra RM, Angulo FJ, Tauxe RV, Widdowson MA, Roy SL, et al. Foodborne illness acquired in the United States – Major pathogens. Emerg Infect Dis 2011;17:7-15.  Back to cited text no. 10
Kaushik K, Khurana S, Wanchu A, Malla N. Lymphoproliferative and cytokine responses to Cryptosporidium parvum in patients coinfected with C. parvum and human immunodeficiency virus. Clin Vaccine Immunol 2009;16:116-21.  Back to cited text no. 11
Udgiri N, Minz M, Kashyap R, Heer M, Gupta CS, Mohandas K, et al. Intestinal cryptosporidiasis in living related renal transplant recipients. Transplant Proc 2004;36:2128-9.  Back to cited text no. 12
Hong DK, Wong CJ, Gutierrez K. Severe cryptosporidiosis in a seven-year-old renal transplant recipient: Case report and review of the literature. Pediatr Transplant 2007;11:94-100.  Back to cited text no. 13
Chieffi PP, Sens YA, Paschoalotti MA, Miorin LA, Silva HG, Jabur P. Infection by Cryptosporidium parvum in renal patients submitted to renal transplant or hemodialysis. Rev Soc Bras Med Trop 1998;31:333-7.  Back to cited text no. 14
Khalil-ur-Rahman, Al-Amoudi A, Badreddine S, Al-Shehri AM, Kanaan H, Al-Ghamdi SM. Cryptosporidiosis in a renal transplant patient treated with paromomycin. Ann Saudi Med 2007;27:373-4.  Back to cited text no. 15
Pérez C, Mocarquer A, Morales J, Miranda C, Apt W, Gomez L, et al. Parasitic infections in renal transplantation patients. Rev Med Chil 1989;117:997-1001.  Back to cited text no. 16
Roncoroni AJ, Gomez MA, Mera J, Cagnoni P, Michel MD. Cryptosporidium infection in renal transplant patients. J Infect Dis 1989;160:559.  Back to cited text no. 17
Sanad MM, Al-Malki JS. Cryptosporidiosis among immunocompromised patients in Saudi Arabia. J Egypt Soc Parasitol 2007;37:765-74.  Back to cited text no. 18
Nagaraj N, Kahan B, Adler DG. Gastrointestinal complications in renal transplant patients: A large, single-center experience. Dig Dis Sci 2007;52:3394-5.  Back to cited text no. 19
Florescu DF, Sandkovsky U. Cryptosporidium infection in solid organ transplantation. World J Transplant 2016;6:460-71.  Back to cited text no. 20
Bhadauria D, Goel A, Kaul A, Sharma RK, Gupta A, Ruhela V, et al. Cryptosporidium infection after renal transplantation in an endemic area. Transpl Infect Dis 2015;17:48-55.  Back to cited text no. 21
Arslan H, Inci EK, Azap OK, Karakayali H, Torgay A, Haberal M. Etiologic agents of diarrhea in solid organ recipients. Transpl Infect Dis 2007;9:270-5.  Back to cited text no. 22
Bandin F, Kwon T, Linas MD, Guigonis V, Valentin A, Cassaing S, et al. Cryptosporidiosis in paediatric renal transplantation. Pediatr Nephrol 2009;24:2245-55.  Back to cited text no. 23
Avery RK, Michaels MG; AST Infectious Diseases Community of Practice. Strategies for safe living after solid organ transplantation. Am J Transplant 2013;13 Suppl 4:304-10.  Back to cited text no. 24
Schwartz BS, Mawhorter SD; AST Infectious Diseases Community of Practice. Parasitic infections in solid organ transplantation. Am J Transplant 2013;13 Suppl 4:280-303.  Back to cited text no. 25
Vandenberg O, Robberecht F, Dauby N, Moens C, Talabani H, Dupont E, et al. Management of a Cryptosporidium hominis outbreak in a daycare center. Pediatr Infect Dis J 2012;31:10-5.  Back to cited text no. 26
Chappell CL, Okhuysen PC. Cryptosporidiosis. Curr Opin Infect Dis 2002;15:523-7.  Back to cited text no. 27
Sponseller JK, Griffiths JK, Tzipori S. The evolution of respiratory cryptosporidiosis: Evidence for transmission by inhalation. Clin Microbiol Rev 2014;27:575-86.  Back to cited text no. 28
Shirley DA, Moonah SN, Kotloff KL. Burden of disease from cryptosporidiosis. Curr Opin Infect Dis 2012;25:555-63.  Back to cited text no. 29
Dillingham RA, Lima AA, Guerrant RL. Cryptosporidiosis: Epidemiology and impact. Microbes Infect 2002;4:1059-66.  Back to cited text no. 30
Artieda J, Basterrechea M, Arriola L, Yagüe M, Albisua E, Arostegui N, et al. Outbreak of cryptosporidiosis in a child day-care centre in Gipuzkoa, Spain, October to December 2011. Euro Surveill 2012;17:20070.  Back to cited text no. 31
Centers for Disease Control (CDC). Cryptosporidiosis among children attending day-care centers – Georgia, Pennsylvania, Michigan, California, New Mexico. MMWR Morb Mortal Wkly Rep 1984;33:599-601.  Back to cited text no. 32
Gormley FJ, Little CL, Chalmers RM, Rawal N, Adak GK. Zoonotic cryptosporidiosis from petting farms, England and Wales, 1992-2009. Emerg Infect Dis 2011;17:151-2.  Back to cited text no. 33
Lange H, Johansen OH, Vold L, Robertson LJ, Anthonisen IL, Nygard K. Second outbreak of infection with a rare Cryptosporidium parvum genotype in schoolchildren associated with contact with lambs/goat kids at a holiday farm in Norway. Epidemiol Infect 2014;142:2105-13.  Back to cited text no. 34
Cantey PT, Kurian AK, Jefferson D, Moerbe MM, Marshall K, Blankenship WR, et al. Outbreak of cryptosporidiosis associated with a man-made chlorinated lake – Tarrant County, Texas, 2008. J Environ Health 2012;75:14-9.  Back to cited text no. 35
Hlavsa MC, Roberts VA, Kahler AM, Hilborn ED, Wade TJ, Backer LC, et al. Recreational water-associated disease outbreaks – United States, 2009-2010. MMWR Morb Mortal Wkly Rep 2014;63:6-10.  Back to cited text no. 36
Bonatti H, Barroso LF 2nd, Sawyer RG, Kotton CN, Sifri CD. Cryptosporidium enteritis in solid organ transplant recipients: Multicenter retrospective evaluation of 10 cases reveals an association with elevated tacrolimus concentrations. Transpl Infect Dis 2012;14:635-48.  Back to cited text no. 37
Newman RD, Sears CL, Moore SR, Nataro JP, Wuhib T, Agnew DA, et al. Longitudinal study of Cryptosporidium infection in children in northeastern Brazil. J Infect Dis 1999;180:167-75.  Back to cited text no. 38
Agnew DG, Lima AA, Newman RD, Wuhib T, Moore RD, Guerrant RL, et al. Cryptosporidiosis in northeastern Brazilian children: Association with increased diarrhea morbidity. J Infect Dis 1998;177:754-60.  Back to cited text no. 39
Chalmers RM, Katzer F. Looking for Cryptosporidium: The application of advances in detection and diagnosis. Trends Parasitol 2013;29:237-51.  Back to cited text no. 40
Xiao L. Molecular epidemiology of cryptosporidiosis: An update. Exp Parasitol 2010;124:80-9.  Back to cited text no. 41
Bouzid M, Tyler KM, Christen R, Chalmers RM, Elwin K, Hunter PR. Multi-locus analysis of human infective Cryptosporidium species and subtypes using ten novel genetic loci. BMC Microbiol 2010;10:213.  Back to cited text no. 42
Elwin K, Hadfield SJ, Robinson G, Chalmers RM. The epidemiology of sporadic human infections with unusual cryptosporidia detected during routine typing in England and Wales, 2000-2008. Epidemiol Infect 2012;140:673-83.  Back to cited text no. 43
Moore JA, Frenkel JK. Respiratory and enteric cryptosporidiosis in humans. Arch Pathol Lab Med 1991;115:1160-2.  Back to cited text no. 44
Okhuysen PC, Chappell CL. Cryptosporidium virulence determinants – Are we there yet? Int J Parasitol 2002;32:517-25.  Back to cited text no. 45
McDonald V, Korbel DS, Barakat FM, Choudhry N, Petry F. Innate immune responses against Cryptosporidium parvum infection. Parasite Immunol 2013;35:55-64.  Back to cited text no. 46
Santaolalla R, Fukata M, Abreu MT. Innate immunity in the small intestine. Curr Opin Gastroenterol 2011;27:125-31.  Back to cited text no. 47
Pantenburg B, Dann SM, Wang HC, Robinson P, Castellanos-Gonzalez A, Lewis DE, et al. Intestinal immune response to human Cryptosporidium sp. infection. Infect Immun 2008;76:23-9.  Back to cited text no. 48
Farthing MJ. Clinical aspects of human cryptosporidiosis. Contrib Microbiol 2000;6:50-74.  Back to cited text no. 49
McDonald V. Host cell-mediated responses to infection with Cryptosporidium. Parasite Immunol 2000;22:597-604.  Back to cited text no. 50
McDonald V, Smith R, Robinson H, Bancroft G. Host immune responses against Cryptosporidium. Contrib Microbiol 2000;6:75-91.  Back to cited text no. 51
Kothavade RJ. Challenges in understanding the immunopathogenesis of Cryptosporidium infections in humans. Eur J Clin Microbiol Infect Dis 2011;30:1461-72.  Back to cited text no. 52
Pantenburg B, Castellanos-Gonzalez A, Dann SM, Connelly RL, Lewis DE, Ward HD, et al. Human CD8(+) T cells clear Cryptosporidium parvum from infected intestinal epithelial cells. Am J Trop Med Hyg 2010;82:600-7.  Back to cited text no. 53
Flanigan T, Whalen C, Turner J, Soave R, Toerner J, Havlir D, et al. Cryptosporidium infection and CD4 counts. Ann Intern Med 1992;116:840-2.  Back to cited text no. 54
Krause I, Amir J, Cleper R, Dagan A, Behor J, Samra Z, et al. Cryptosporidiosis in children following solid organ transplantation. Pediatr Infect Dis J 2012;31:1135-8.  Back to cited text no. 55
Ziring D, Tran R, Edelstein S, McDiarmid SV, Gajjar N, Cortina G, et al. Infectious enteritis after intestinal transplantation: Incidence, timing, and outcome. Transplantation 2005;79:702-9.  Back to cited text no. 56
Tran MQ, Gohh RY, Morrissey PE, Dworkin LD, Gautam A, Monaco AP, et al. Cryptosporidium infection in renal transplant patients. Clin Nephrol 2005;63:305-9.  Back to cited text no. 57
Pozio E, Rivasi F, Cacciò SM. Infection with Cryptosporidium hominis and reinfection with Cryptosporidium parvum in a transplanted ileum. APMIS 2004;112:309-13.  Back to cited text no. 58
Abdo A, Klassen J, Urbanski S, Raber E, Swain MG. Reversible sclerosing cholangitis secondary to cryptosporidiosis in a renal transplant patient. J Hepatol 2003;38:688-91.  Back to cited text no. 59
Gerber DA, Green M, Jaffe R, Greenberg D, Mazariegos G, Reyes J. Cryptosporidial infections after solid organ transplantation in children. Pediatr Transplant 2000;4:50-5.  Back to cited text no. 60
Campos M, Jouzdani E, Sempoux C, Buts JP, Reding R, Otte JB, et al. Sclerosing cholangitis associated to cryptosporidiosis in liver-transplanted children. Eur J Pediatr 2000;159:113-5.  Back to cited text no. 61
Rodríguez Ferrero ML, Muñoz P, Valerio M, Bouza E, Martín-Rabadán P, Anaya F. Cryptosporidium parvum infection in a kidney transplant recipient. Nefrologia 2010;30:476-7.  Back to cited text no. 62
Acikgoz Y, Ozkaya O, Bek K, Genc G, Sensoy SG, Hokelek M. Cryptosporidiosis: A rare and severe infection in a pediatric renal transplant recipient. Pediatr Transplant 2012;16:E115-9.  Back to cited text no. 63
Clifford CP, Crook DW, Conlon CP, Fraise AP, Day DG, Peto TE. Impact of waterborne outbreak of cryptosporidiosis on AIDS and renal transplant patients. Lancet 1990;335:1455-6.  Back to cited text no. 64
Dupont C, Bougnoux ME, Turner L, Rouveix E, Dorra M. Microbiological findings about pulmonary cryptosporidiosis in two AIDS patients. J Clin Microbiol 1996;34:227-9.  Back to cited text no. 65
Giang TT, Pollack G, Kotler DP. Cryptosporidiosis of the nasal mucosa in a patient with AIDS. AIDS 1994;8:555-6.  Back to cited text no. 66
Harari MD, West B, Dwyer B. Cryptosporidium as cause of laryngotracheitis in an infant. Lancet 1986;1:1207.  Back to cited text no. 67
Pellicelli AM, Palmieri F, Spinazzola F, D'Ambrosio C, Causo T, De Mori P, et al. Pulmonary cryptosporidiosis in patients with acquired immunodeficiency syndrome. Minerva Med 1998;89:173-5.  Back to cited text no. 68
Azizi L, Raynal M, Cazejust J, Ruiz A, Menu Y, Arrivé L. MR Imaging of sclerosing cholangitis. Clin Res Hepatol Gastroenterol 2012;36:130-8.  Back to cited text no. 69
Baishanbo A, Gargala G, Duclos C, François A, Rossignol JF, Ballet JJ, et al. Efficacy of nitazoxanide and paromomycin in biliary tract cryptosporidiosis in an immunosuppressed gerbil model. J Antimicrob Chemother 2006;57:353-5.  Back to cited text no. 70
Ditrich O, Palkovic L, Stĕrba J, Prokopic J, Loudová J, Giboda M. The first finding of Cryptosporidium baileyi in man. Parasitol Res 1991;77:44-7.  Back to cited text no. 71
Hayward AR, Levy J, Facchetti F, Notarangelo L, Ochs HD, Etzioni A, et al. Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM. J Immunol 1997;158:977-83.  Back to cited text no. 72
Hunter PR, Nichols G. Epidemiology and clinical features of Cryptosporidium infection in immunocompromised patients. Clin Microbiol Rev 2002;15:145-54.  Back to cited text no. 73
Kocoshis SA, Cibull ML, Davis TE, Hinton JT, Seip M, Banwell JG. Intestinal and pulmonary cryptosporidiosis in an infant with severe combined immune deficiency. J Pediatr Gastroenterol Nutr 1984;3:149-57.  Back to cited text no. 74
Khurana S, Sharma P, Sharma A, Malla N. Evaluation of Ziehl-Neelsen staining, auramine phenol staining, antigen detection enzyme linked immunosorbent assay and polymerase chain reaction, for the diagnosis of intestinal cryptosporidiosis. Trop Parasitol 2012;2:20-3.  Back to cited text no. 75
[PUBMED]  [Full text]  
Chalmers RM, Atchison C, Barlow K, Young Y, Roche A, Manuel R. An audit of the laboratory diagnosis of cryptosporidiosis in England and Wales. J Med Microbiol 2015;64:688-93.  Back to cited text no. 76
Chalmers RM, Campbell BM, Crouch N, Charlett A, Davies AP. Comparison of diagnostic sensitivity and specificity of seven Cryptosporidium assays used in the UK. J Med Microbiol 2011;60:1598-604.  Back to cited text no. 77
Garcia LS, Shimizu RY. Evaluation of nine immunoassay kits (enzyme immunoassay and direct fluorescence) for detection of Giardia lamblia and Cryptosporidium parvum in human fecal specimens. J Clin Microbiol 1997;35:1526-9.  Back to cited text no. 78
García-Bujalance S, García-Gil V, Baquero-Artigao F. Microbiological diagnosis of Cryptosporidium spp. and Giardia intestinalis in paediatrics. Enferm Infecc Microbiol Clin 2013;31:193-4.  Back to cited text no. 79
Johnston SP, Ballard MM, Beach MJ, Causer L, Wilkins PP. Evaluation of three commercial assays for detection of Giardia and Cryptosporidium organisms in fecal specimens. J Clin Microbiol 2003;41:623-6.  Back to cited text no. 80
Helmy YA, Krücken J, Nöckler K, von Samson-Himmelstjerna G, Zessin KH. Comparison between two commercially available serological tests and polymerase chain reaction in the diagnosis of Cryptosporidium in animals and diarrhoeic children. Parasitol Res 2014;113:211-6.  Back to cited text no. 81
Weitzel T, Dittrich S, Möhl I, Adusu E, Jelinek T. Evaluation of seven commercial antigen detection tests for Giardia and Cryptosporidium in stool samples. Clin Microbiol Infect 2006;12:656-9.  Back to cited text no. 82
Khare R, Espy MJ, Cebelinski E, Boxrud D, Sloan LM, Cunningham SA, et al. Comparative evaluation of two commercial multiplex panels for detection of gastrointestinal pathogens by use of clinical stool specimens. J Clin Microbiol 2014;52:3667-73.  Back to cited text no. 83
Elwin K, Robinson G, Hadfield SJ, Fairclough HV, Iturriza-Gómara M, Chalmers RM. A comparison of two approaches to extracting Cryptosporidium DNA from human stools as measured by a real-time PCR assay. J Microbiol Methods 2012;89:38-40.  Back to cited text no. 84
Hadfield SJ, Robinson G, Elwin K, Chalmers RM. Detection and differentiation of Cryptosporidium spp. in human clinical samples by use of real-time PCR. J Clin Microbiol 2011;49:918-24.  Back to cited text no. 85
Current WL, Garcia LS. Cryptosporidiosis. Clin Lab Med 1991;11:873-97.  Back to cited text no. 86
Checkley W, White AC Jr., Jaganath D, Arrowood MJ, Chalmers RM, Chen XM, et al. A review of the global burden, novel diagnostics, therapeutics, and vaccine targets for cryptosporidium. Lancet Infect Dis 2015;15:85-94.  Back to cited text no. 87
Abubakar I, Aliyu SH, Arumugam C, Hunter PR, Usman NK. Prevention and treatment of cryptosporidiosis in immunocompromised patients. Cochrane Database Syst Rev 2007;(1):CD004932.  Back to cited text no. 88
Maezono S, Sugimoto K, Sakamoto K, Ohmori M, Hishikawa S, Mizuta K, et al. Elevated blood concentrations of calcineurin inhibitors during diarrheal episode in pediatric liver transplant recipients: Involvement of the suppression of intestinal cytochrome P450 3A and P-glycoprotein. Pediatr Transplant 2005;9:315-23.  Back to cited text no. 89
Cabada MM, White AC Jr. Treatment of cryptosporidiosis: Do we know what we think we know? Curr Opin Infect Dis 2010;23:494-9.  Back to cited text no. 90
Rossignol JF, Ayoub A, Ayers MS. Treatment of diarrhea caused by Cryptosporidium parvum: A prospective randomized, double-blind, placebo-controlled study of Nitazoxanide. J Infect Dis 2001;184:103-6.  Back to cited text no. 91
Rossignol JF, Kabil SM, el-Gohary Y, Younis AM. Effect of nitazoxanide in diarrhea and enteritis caused by Cryptosporidium species. Clin Gastroenterol Hepatol 2006;4:320-4.  Back to cited text no. 92
Clinton White A. Cryptosporidiosis (Cryptosporidium species). In: Bennett JF, Dolin R, Blaser MJ, editors. Mandell, Douglas, Bennett's, Principles and Practice of Infectious Diseases: Expert Consult Premium. 8th ed. Philadelphia, PA: Curchil Livingstone; 2015. p. 3173-83.  Back to cited text no. 93
White AC Jr., Cron SG, Chappell CL. Paromomycin in cryptosporidiosis. Clin Infect Dis 2001;32:1516-7.  Back to cited text no. 94
Sáez-Llorens X, Odio CM, Umaña MA, Morales MV. Spiramycin vs. placebo for treatment of acute diarrhea caused by Cryptosporidium. Pediatr Infect Dis J 1989;8:136-40.  Back to cited text no. 95
Wittenberg DF, Miller NM, van den Ende J. Spiramycin is not effective in treating cryptosporidium diarrhea in infants: Results of a double-blind randomized trial. J Infect Dis 1989;159:131-2.  Back to cited text no. 96
Allam AF, Shehab AY. Efficacy of azithromycin, praziquantel and mirazid in treatment of cryptosporidiosis in school children. J Egypt Soc Parasitol 2002;32:969-78.  Back to cited text no. 97
Blanshard C, Shanson DC, Gazzard BG. Pilot studies of azithromycin, letrazuril and paromomycin in the treatment of cryptosporidiosis. Int J STD AIDS 1997;8:124-9.  Back to cited text no. 98
Hicks P, Zwiener RJ, Squires J, Savell V. Azithromycin therapy for Cryptosporidium parvum infection in four children infected with human immunodeficiency virus. J Pediatr 1996;129:297-300.  Back to cited text no. 99
Nachbaur D, Kropshofer G, Feichtinger H, Allerberger F, Niederwieser D. Cryptosporidiosis after CD34-selected autologous peripheral blood stem cell transplantation (PBSCT). Treatment with paromomycin, azithromycin and recombinant human interleukin-2. Bone Marrow Transplant 1997;19:1261-3.  Back to cited text no. 100
Giacometti A, Cirioni O, Barchiesi F, Ancarani F, Scalise G. Activity of nitazoxanide alone and in combination with azithromycin and rifabutin against Cryptosporidium parvum in cell culture. J Antimicrob Chemother 2000;45:453-6.  Back to cited text no. 101
Korich DG, Mead JR, Madore MS, Sinclair NA, Sterling CR. Effects of ozone, chlorine dioxide, chlorine, and monochloramine on Cryptosporidium parvum oocyst viability. Appl Environ Microbiol 1990;56:1423-8.  Back to cited text no. 102
Centers for Disease Control (CDC). Cryptosporidium Preventionand Control. Available from: http://www.cdc.gov/parasites/crypto/gen_info/prevention-general-public.html. [Last accessed on 2019 Oct 07].  Back to cited text no. 103
Okhuysen PC, Chappell CL, Crabb J, Valdez LM, Douglass ET, DuPont HL. Prophylactic effect of bovine anti-Cryptosporidium hyperimmune colostrum immunoglobulin in healthy volunteers challenged with Cryptosporidium parvum. Clin Infect Dis 1998;26:1324-9.  Back to cited text no. 104
Mead JR. Challenges and prospects for a Cryptosporidium vaccine. Future Microbiol 2010;5:335-7.  Back to cited text no. 105
Okhuysen PC, Chappell CL, Sterling CR, Jakubowski W, DuPont HL. Susceptibility and serologic response of healthy adults to reinfection with Cryptosporidium parvum. Infect Immun 1998;66:441-3.  Back to cited text no. 106
Miyamoto Y, Eckmann L. Drug development against the major diarrhea-causing parasites of the small intestine, Cryptosporidium and Giardia. Front Microbiol 2015;6:1208.  Back to cited text no. 107
Costa LB, Noronha FJ, Roche JK, Sevilleja JE, Warren CA, Oriá R, et al. Novel in vitro and in vivo models and potential new therapeutics to break the vicious cycle of Cryptosporidium infection and malnutrition. J Infect Dis 2012;205:1464-71.  Back to cited text no. 108
Ludington JG, Ward HD. Systemic and mucosal immune responses to Cryptosporidium-vaccine development. Curr Trop Med Rep 2015;2:171-80.  Back to cited text no. 109
Sawant M, Baydoun M, Creusy C, Chabé M, Viscogliosi E, Certad G, et al. Cryptosporidium and colon cancer: Cause or consequence? Microorganisms 2020;8:1665.  Back to cited text no. 110
Kalantari N, Gorgani-Firouzjaee T, Ghaffari S, Bayani M, Ghaffari T, Chehrazi M. Association between Cryptosporidium infection and cancer: A systematic review and meta-analysis. Parasitol Int 2020;74:101979.  Back to cited text no. 111


  [Figure 1], [Figure 2]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
Transmission and...
Clinical Features
Extraintestinal ...
General Management
Modulation of Im...
Antiparasitic Agents
Future Perspectives
Article Figures

 Article Access Statistics
    PDF Downloaded97    
    Comments [Add]    

Recommend this journal