Blastocystis Research Review

Updated June 1, 2007

 

Contents

 

1. Animal Studies  (click here to view studies)
SUMMARY: Experimental infection with Blastocystis isolates from China in immunocompetent and immunocompromised mice produced intense intestinal inflammation, invasive infection, and death in some animals.  An earlier study with an isolate from Malaysia showed intense intestinal inflammation, lethargy, and weight loss but not death.  The practice of classifying every Blastocystis isolate from a human as Blastocystis hominis has resulted in many different species of Blastocystis being named the same thing.  As such, it is possible that a study performed by another researcher could produce conflicting results.

2. Pathogenicity and Phylogenetics (click here to view studies)
SUMMARY: Seven genetically distinct organisms have been classified under the name Blastocystis hominis.  These organisms have different number of chromosomes and exhibit different behavior in culture.  The current consensus created by comparing different studies indicates that (Yoshikawa) subtypes 1, 3, and 7 are pathogenic in humans while Subtype 5 is harmless in humans.  The pathogenic subtypes are associated with farm animals, cattle, and rodents.  The pathogenic types of Blastocystis produce large highly adhesive amoeboid forms in culture, while the non-pathogenic types produce small vacuolar forms.  Humans infected with symptomatic Blastocystis exhibit a substantially elevated immune response to the Blastocystis antigen, a polysaccharide present on the cell surface.  This response is not seen in asymptomatic infections.

3. Prevalence and Epidemiology (click here to view studies)
SUMMARY: In the United States, the prevalence of Blastocystis increased by a factor of 10 between 1987 and 2000.  Originally found in about 2.6% of stool samples submitted to labs, it is now found in 23% of the samples.  In contrast, the prevalence of Giardia decreased over this period.  Symptomatic Blastocystis infection is associated with travel to less developed countries and exposure to untreated water.  Various surveys exist as to the prevalence, but it is difficult to judge their significance, because they use methods which under-detect pathogenic infection (see DETECTION below).  One survey in Japan found that over 50% of Blastocystis infections in humans were with Subtype 5, which is harmless.   The pathogenic subtypes, especially Subtype 3, may be more prevalent in less developed countries, but is probably growing in prevalence in developed countries due to the failure of the public health system to address this problem.


4. Detection (click here to view studies)
SUMMARY: The sensitivity of direct microscopy in the detection of Blastocystis is poor.  Depending on the method used, sensitivities of 16% to 44% has been recorded.  Stool culture is a superior method, but even that fails to detect many infections.  The most reliable method is direct PCR testing of stool specimens.  Co-infection is common in Blastocystis, and culture may distort the type of Blastocystis detected, as some types will overgrow others in culture.

 

5. Case Studies/Case Reports (click here to view studies)
SUMMARY:

 

6. Pathogenesis (click here to view studies)
SUMMARY: Blastocystis

 

7. Undiagnosed Blastocystis infection as the cause of irritable bowel syndrome  (click here to view studies)
SUMMARY: IBS patients are found to be disproportionately infected with Blastocystis.  When more sensitive techniques are used, the relationship becomes stronger.
 

 

1. Animal Studies

Reference Summary Abstract
Zhang HW, Li W, Yan QY, He LJ, Su YP.  Impact of blastocystis hominis infection on ultrastructure of intestinal mucosa in mice.  Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2006 Jun;24(3):187-91. PMID: 17094618
 
  • Mice were infected with an unspecified type of Blastocystis
  • Infection was demonstrated to be invasive
  • Intestinal mucosa was badly damaged
  • The subtype was not specified, but judging by severity of infection, it is likely to be Yoshikawa Subtype 1 or 3.  These are the most common pathogenic types in the Far East.
 Abstract
Yao FR, Qiao JY, Zhao Y, Zhang X, Yang JH, Li XQ. Experimental infection of mice with Blastocystis hominis.   Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2005 Dec 30;23(6):444-8. 
PMID: 16566218
  • Mice were infected with unspecified type of Blastocystis
  • Infected mice showed weight loss and lethargy
  • NOTE: These are two symptoms seen in humans, but chronically (i.e. chronic fatigue syndrome and uncontrollable weight loss)
  • Some mice died
  • Severe edema was seen through the entire digestive tract
Abstract
Moe KT, Singh M, Howe J, Ho LC, Tan SW, Chen XQ, Ng GC, Yap EH. Experimental Blastocystis hominis infection in laboratory mice.
Parasitol Res. 1997;83(4):319-25.
PMID: 9134552
 
  • Mice were infected with unspecified type of Blastocystis
  • Infected mice showed weight loss and lethargy

 

 

 Abstract

 

 

2. Pathogenicity and Phylogenetics

 

Commentary: All the subtype numbers used in this section are Yoshikawa subtypes.  To translate subtype numbers between different papers, you may use the table below.  For a good table of isolates, see the Noel paper.

The color coding in the table below represents the consensus view from various research papers regarding the pathogenicity of Blastocystis subtypes.

It should, perhaps, be expected that the non-pathogenic type in humans is the type which is primarily found in primates.  It is likely this type has evolved over time to be harmless to humans and primates (humans are primates, by the way).  Unfortunately, it appears that humans have some kind of deficiency in our gastrointestinal immunity, because we can become infected with every subtype of Blastocystis.  The same is not true of other animals.  For example, only Subtype 7 can infect rodents.    The pathogenic type of Blastocystis has been shown to produce large highly adhesive amoeboid forms.  These forms may represent aggressive methods needed to parasitize rodents and cattle, but which are unnecessary in humans.  In humans, these forms cause disease and actually interfere with the ability of the parasite to reproduce.  For this reason, it may be difficult to detect symptomatic infections in humans.

Yoshikawa Subtype Number Arisue Clade Number (used in Kaneda paper) Stensvold Cluster Standardized Number from Stensvold, 2007
1 I E Blastocystis sp. subtype 1
2 VII   Blastocystis sp. subtype 7
3 III A Blastocystis sp. subtype 3
4 VI   Blastocystis sp. subtype 6
5 II C,D Blastocystis sp. subtype 2
6 V   Blastocystis sp. subtype 5
7 IV B Blastocystis sp. subtype 7

 

Reference Summary Abstract
Kaneda Y, Horiki N, Cheng XJ, Fujita Y, Maruyama M, Tachibana H.
Ribodemes of Blastocystis hominis isolated in Japan. Am J Trop Med Hyg. 2001 Oct;65(4):393-6.
PMID: 11693890
 
  • Subtypes 1, 3 and 4 (Farm Animals and one Avian)are pathogenic (50% of people infected get sick)
     
  • The Primate Subtype is commensal in humans (>90% of carriers show no symptoms)
     
  • Over half of the infections in Japan are with the Primate Subtype
     
  • NOTE: Paper uses Arisue subtype numbers, not Yoshikawa subtype numbers.  For conversion, see table above.
 Abstract

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Full
Paper
 
Puthia MK, Sio SW, Lu J, Tan KS.
Blastocystis ratti induces contact-independent apoptosis, F-actin rearrangement, and barrier function disruption in IEC-6 cells.
Infect Immun. 2006 Jul;74(7):4114-23. PMID: 16790785
 
  • Summary: Subtype 7 (The Rodent Subtype) is pathogenic
 Abstract
Stensvold R, Brillowska-Dabrowska A, Nielsen HV, Arendrup MC.
Detection of Blastocystis hominis in unpreserved stool specimens by using polymerase chain reaction.
J Parasitol. 2006 Oct;92(5):1081-7.
PMID: 17152954
 
  • Summary: Subtypes 3 and 7 are associated with symptoms
     
  • Patients with diarrhea associated with Blastocystis infection with no other pathogens found are primarily infected with Yoshikawa Subtypes 3 and 7. 
     
  • That is, in the patients in whom no other pathogens were found, Blastocystis subtypes 3 and 7 (Stensvold groups A and B)  were found multiple times.
     
  • Almost half of infections can not be detected with direct microscopy.  Direct testing of stool specimens by PCR is more reliable.
     
  • Blastocystis cells may resemble human fat cells or leukocytes, making identification difficult
     
  • A great deal of genetic diversity exists in ribosomal DNA of Blastocystis
 Abstract
Tan TC, Suresh KG, Thong KL, Smith HV.  PCR fingerprinting of Blastocystis isolated from symptomatic and asymptomatic human hosts. Parasitol Res. 2006 Sep;99(4):459-65. Epub 2006 Apr 21.
PMID: 16628457
 
  • Subtypes 1 and 3  are pathogenic
     
  • Blastocystis variants from symptomatic and asymptomatic subjects were genotyped
     
  • The isolates from symptomatic patients fell into a separate phylogenetic branch.
     
  • The amoeboid isolates were all of Subtype 3 (this wasn't in the paper - I called Dr. Kumar and asked him).
     
  • Dr. Kumar has also seen symptomatic patients with Yoshikawa subtype 1, but only in cancer patients.  These isolates produced amoeboid forms as well.
     
 Abstract
Tan TC, Suresh KG.  Predominance of amoeboid forms of Blastocystis hominis in isolates from symptomatic patients. Parasitol Res. 2006 Feb;98(3):189-93. Epub 2005 Dec 2.
PMID: 16323025
 
  • Blastocystis isolates from 10 asymptomatic and 10 symptomatic patients were cultured in a special culture designed to reproduce the intestinal environment (i.e. they were cultured with other bacteria)
     
  • All the isolates from symptomatic patients produced huge amoeboid forms that were highly adhesive (see below reference for details)
     
  • All the isolates from asymptomatic patients produced small vacuolar forms

 

 Abstract
Tan TC, Suresh KG. Amoeboid form of Blastocystis hominis - a detailed ultrastructural insight. Parasitol Res. 2006 Nov;99(6):737-42. Epub 2006 Jul 1. PMID: 16816959
 
  • Detailed electronic microscopic photographs of amoeboid forms from above study
     
  • Paper demonstrates two types of amoeboid forms in pathogenic Blastocystis
 Abstract
     
Noel C, Dufernez F, Gerbod D, Edgcomb VP, Delgado-Viscogliosi P, Ho LC, Singh M, Wintjens R, Sogin ML, Capron M, Pierce R, Zenner L, Viscogliosi E.  Molecular phylogenies of Blastocystis isolates from different hosts: implications for genetic diversity, identification of species, and zoonosis. J Clin Microbiol. 2005 Jan;43(1):348-55.  PMID: 15634993
 
  • The organism that pathologists identify as Blastocystis hominis can be one of seven genetically distinct organisms
     
  • The genetic distance between these is great enough to allow them to be considered individual species
     
  • The different subtypes show some host specificity, but unfortunately, humans are able to contract them all.
     
  • Every subtype can infect humans, the descriptive phrases below focus on the non-human organisms that are able to be infected with these parasites.
     
    • Subtype 1: Farm animals (pigs, chickens, cattle)
       
    • Subtype 2: Avian (Quail and Goose)
       
    • Subtype 3: Cattle
       
    • Subtype 4: Avian (Chicken, Quail, Turkey)
       
    • Subtype 5: Primate (Monkeys)
       
    • Subtype 6: Pigs and Cattle
       
    • Subtype 7: Rodents (includes Blastocystis ratti)
       
  • NOTE: The Parkar study (below) was the first one to find Subtype 6 in humans.
     
  • Isolates genetically identical to Blastocystis ratti were recovered from humans and labeled Blastocystis hominis by pathologists.
     
  • "In conclusion, our data confirm that extensive genetic diversity exists among Blastocystis isolates from humans and other animals and suggest that more than one species could infect humans. Moreover, our findings emphasize the low host specificity of this organism and indicate that numerous human Blastocystis infections may be of zoonotic origin. Thus, the number and range of animals found to be infected by Blastocystis may represent a huge potential reservoir for infection of humans."
 Abstract

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3. Prevalence and Epidemiology

 

Reference Summary Abstract
Amin OM.  Seasonal prevalence of intestinal parasites in the United States during 2000. Am J Trop Med Hyg. 2002 Jun;66(6):799-803. PMID: 12224595
 		 In 2000, Giardia was found in 0.65% of stool samples submitted to this lab.  Blastocystis was found in 23% (662/2896 patients) Abstract

Download Paper
Kappus KK, Juranek DD, Roberts JM. Results of testing for intestinal parasites by state diagnostic laboratories, United States, 1987.
MMWR CDC Surveill Summ. 1991 Dec;40(4):25-45. PMID: 1779956
 		 In 1987, Giardia was found in 7.2% of stool samples submitted to state diagnostic laboratories.  Blastocystis was found in 2.6% of samples. Abstract

Download Paper

 

 

 

4. Detection/Diagnosis

 

Reference Summary Abstract
Stensvold R, Brillowska-Dabrowska A, Nielsen HV, Arendrup MC.
Detection of Blastocystis hominis in unpreserved stool specimens by using polymerase chain reaction.
J Parasitol. 2006 Oct;92(5):1081-7.
PMID: 17152954
 
  • GOLD STANDARD: Direct PCR testing of stool specimens
     
  • Sensitivity of direct microscopy: 66%
     
  • Sensitivity of stool culture: 83%
     
  • NOTE: These findings support the hypothesis of a recent zoonotic transmission for the pathogenic variants of Blastocystis.  17% of the infections are not able to even be cultured from their hosts, suggesting an organism that does not complete its life cycle in the host, and is poorly adapted to that environment.
     
 Abstract
Parkar U, Traub RJ, Kumar S, Mungthin M, Vitali S, Leelayoova S, Morris K, Thompson RC.
Direct characterization of Blastocystis from faeces by PCR and evidence of zoonotic potential. Parasitology. 2007 Mar;134(Pt 3):359-67. Epub 2006 Oct 19. PMID: 17052374
 
  • Direct testing of stool specimens by PCR is the best way identified so far for detecting Blastocystis
     
  • Co-infections exist in some cases, and culturing specimens distorted the genotype of Blastocystis isolated
     
  • Isolates with 99% genetic similarity were found in humans and animals, proving the existence of zoonosis
 Abstract
 
Leelayoova S, Taamasri P, Rangsin R, Naaglor T, Thathaisong U, Mungthin M. In-vitro cultivation: a sensitive method for detecting Blastocystis hominis. Ann Trop Med Parasitol. 2002 Dec;96(8):803-7.
PMID: 12625935
 
  • GOLD STANDARD: Stool Culture
     
  • Sensitivity of smear: 43%
     
  • Sensitivity when concentration techniques used: 19%
 Abstract
Termmathurapoj S, Leelayoova S, Aimpun P, Thathaisong U, Nimmanon T, Taamasri P, Mungthin M.
The usefulness of short-term in vitro cultivation for the detection and molecular study of Blastocystis hominis in stool specimens.
Parasitol Res. 2004 Aug;93(6):445-7. Epub 2004 Jul 9.
PMID: 15243800
 
  • GOLD STANDARD: Culture
     
  • Sensitivity of stain: 40%
     
  • Sensitivity of smear: 16.7%

 

 Abstract

 

 

 

5. Case Studies / Case Reports

 

Reference Summary Abstract
Qadri SM, al-Okaili GA, al-Dayel F.
Clinical significance of Blastocystis hominis. J Clin Microbiol. 1989 Nov;27(11):2407-9. PMID: 2808664
 		 Symptoms listed below

All patients recovered with Metronidazole (not true for later studies)

 Abstract

Full Paper
Nimri LF.  Evidence of an epidemic of Blastocystis hominis infections in preschool children in northern Jordan.
J Clin Microbiol. 1993 Oct;31(10):2706-8. PMID: 8253970
 		   Abstract

Full paper
Nimri L, Batchoun R. Intestinal colonization of symptomatic and asymptomatic schoolchildren with Blastocystis hominis.
J Clin Microbiol. 1994 Nov;32(11):2865-6.PMID: 7852590
 		   Abtract

Full Paper
El-Shazly AM, Abdel-Magied AA, El-Beshbishi SN, El-Nahas HA, Fouad MA, Monib MS.
Blastocystis hominis among symptomatic and asymptomatic individuals in Talkha Center, Dakahlia Governorate, Egypt.
J Egypt Soc Parasitol. 2005 Aug;35(2):653-66.
PMID: 16083074
 		   Abstract
Moghaddam DD, Ghadirian E, Azami M. Blastocystis hominis and the evaluation of efficacy of metronidazole and trimethoprim/sulfamethoxazole.
Parasitol Res. 2005 Jun;96(4):273-5. Epub 2005 May 25.
PMID: 15915364
 		   Abstract
 
Armentia A, Mendez J, Gomez A, Sanchis E, Fernandez A, de la Fuente R, Sanchez P. Urticaria by Blastocystis hominis. Successful treatment with paromomycin.
Allergol Immunopathol (Madr). 1993 Jul-Aug;21(4):149-51.
PMID: 8237719
 		 Cutaneous involvement in Blastocystis Abstract
Biedermann T, Hartmann K, Sing A, Przybilla B. Hypersensitivity to non-steroidal anti-inflammatory drugs and chronic urticaria cured by treatment of Blastocystis hominis infection.
Br J Dermatol. 2002 Jun;146(6):1113-4. PMID: 12072100
 		 Cutaneous involvement in Blastocystis Citation
Pasqui AL, Savini E, Saletti M, Guzzo C, Puccetti L, Auteri A. Chronic urticaria and blastocystis hominis infection: a case report.
Eur Rev Med Pharmacol Sci. 2004 May-Jun;8(3):117-20.
PMID: 15368795
 		 Cutaneous involvement in Blastocystis Abstract
Cassano N, Scoppio BM, Loviglio MC, Vena GA. Remission of delayed pressure urticaria after eradication of Blastocystis hominis.
Acta Derm Venereol. 2005;85(4):357-8. No abstract available.
PMID: 16191864
 		 Cutaneous involvement in Blastocystis Citation
Gupta R, Parsi K. Chronic urticaria due to Blastocystis hominis.
Australas J Dermatol. 2006 May;47(2):117-9. PMID: 16637808
 		 Cutaneous involvement in Blastocystis Abstract
Lee MG, Rawlins SC, Didier M, DeCeulaer K. Infective arthritis due to Blastocystis hominis. Ann Rheum Dis. 1990 Mar;49(3):192-3. PMID: 2322029
 		 Joint pain in Blastocystis Abstract

Full Paper
Kruger K, Kamilli I, Schattenkirchner M. [Blastocystis hominis as a rare arthritogenic pathogen. A case report]
Z Rheumatol. 1994 Mar-Apr;53(2):83-5. German. PMID: 8023590
 		 Joint pain in Blastocystis Abstract

 

 

6. Pathogenesis (how does it cause disease?)

Reference Summary Abstract
Puthia MK, Sio SW, Lu J, Tan KS.
Blastocystis ratti induces contact-independent apoptosis, F-actin rearrangement, and barrier function disruption in IEC-6 cells.
Infect Immun. 2006 Jul;74(7):4114-23. PMID: 16790785
 		 Blastocystis ratti (subtype 7) destroys colonic epithelial cells in culture, and also changes their structure in a way that would cause diarrhea in the host. Abstract
 

Full paper
Sio SW, Puthia MK, Lee AS, Lu J, Tan KS.  Protease activity of Blastocystis hominis. Parasitol Res. 2006 Jul;99(2):126-30. Epub 2006 Mar 4. PMID: 16518611
 
  • Cysteine proteases were found in Blastocystis.
     
  • These function only over a narrow range of pH.
 Abstract
Long HY, Handschack A, Konig W, Ambrosch A.  Blastocystis hominis modulates immune responses and cytokine release in colonic epithelial cells. Parasitol Res. 2001 Dec;87(12):1029-30. PMID: 11763434
 
  • Blastocystis causes colonic epithelial cells to release cytokines, which are inflammatory messengers.  Cytokines found are GM-CSF and IL-8
     
  • NOTE: IL-8 is associated with arthritis
 Abstract

Puthia MK, Vaithilingam A, Lu J, Tan KS. Degradation of human secretory immunoglobulin A by Blastocystis.
Parasitol Res. 2005 Nov;97(5):386-9. Epub 2005 Sep 7. PMID: 16151742
 		   Abstract

 

 

7. Undiagnosed Blastocystis infection as the cause of irritable bowel syndrome

Reference Summary Abstract

Yakoob J, Jafri W, Jafri N, Khan R, Islam M, Beg MA, Zaman V.
Irritable bowel syndrome: in search of an etiology: role of Blastocystis hominis. Am J Trop Med Hyg. 2004 Apr;70(4):383-5. PMID: 15100450
 
  • Microscopy identified Blastocystis in 32% of IBS patients versus 7% of controls
     
  • Stool culture identified Blastocystis in 46% of the cases versus 7% of the controls
 Abstract
 

Full Paper
Hussain R, Jaferi W, Zuberi S, Baqai R, Abrar N, Ahmed A, Zaman V.
Significantly increased IgG2 subclass antibody levels to Blastocystis hominis in patients with irritable bowel syndrome. Am J Trop Med Hyg. 1997 Mar;56(3):301-6.  PMID: 9129532
 
  • IBS patients showed a strongly elevated response to Blastocystis antigen
     
  • The immune response seemed uncorrelated with the ability to identify Blastocystis in stool samples
 Abstract
Giacometti A, Cirioni O, Fiorentini A, Fortuna M, Scalise G.  Irritable bowel syndrome in patients with Blastocystis hominis infection. Eur J Clin Microbiol Infect Dis. 1999 Jun;18(6):436-9.
PMID: 10442423
 
  • Blastocystis infection is strongly linked to irritable bowel syndrome
 Abstract

       

 

 

8. Undiagnosed Blastocystis infection as the cause of inflammatory bowel disease

 

Reference Summary Abstract

 

 

9. Complaints about considering Blastocystis a pathogen

Reference Summary Abstract
Rosenblatt JE.  Blastocystis hominis.
J Clin Microbiol. 1990 Oct;28(10):2379-80. PMID: 2101593
 
  • Stop publishing articles about patients being sick and provide some useful information.
 Full Letter
Markell EK, Udkow MP.
Association of Blastocystis hominis with human disease?
J Clin Microbiol. 1990 May;28(5):1085-6. No abstract available.
PMID: 2351728
 
  • Fatigue, headaches, and depression should not be listed as symptoms of Blastocystis infection
     
  • Pathologists in the Middle East probably can not read slides properly
 Full Letter