Blastocystis hominis: Pathogen or Commensal?

Abstracts & Commentary

Synopsis: Blastocystis hominis, a protozoan parasite, is frequently identified in stools of returned travelers. There is, however, no conclusive evidence that this parasite causes symptoms in humans or that it requires specific treatment.

Sources: Chen T, et al. Clinical characteristics and endoscopic findings associated with Blastocystis hominis in healthy adults. Am J Trop Med Hyg. 2003;69:213-216; Murga-Gutierrez SN, et al. Intestinal parasites associated with acute diarrheal disease in children less than five years of age, from Alto Trujillo, Peru; Marcos L, et al. High rates of infection from intestinal parasites in different regions of Peru and the necessity of control and prevention programs: A public health problem in rural areas; Maco V, et al. Strongyloidiasis in the Amazon: A clinical and epidemiological study in soldiers. All presented to the annual meeting of the American Society of Tropical Medicine and Hygiene. Philadelphia. December 2003.

Chen and associates described the clinical and endoscopic findings associated with Blastocystis hominis infections in immunocompetent adults. They evaluated 99 individuals with stools positive for B hominis but negative for other parasites. These cases were compared with 193 controls who had negative stool exams for parasites. Cases and controls were matched for age, gender, and date of examination. Stool specimens were investigated by a direct wet film method for detection of leukocytes, ova, and parasites. All subjects underwent upper gastrointestinal endoscopy and sigmoidoscopic examination. Most of the subjects with positive stool exam for B hominis were asymptomatic (88%). There was no difference in gastrointestinal symptoms (nausea, abdominal discomfort, flatulence, and diarrhea) among cases or controls (P = .94). None of the subjects with positive stool smears for B hominis had the appearance of colitis or colonic ulceration on sigmoidoscopy. Fecal leukocytes were absent in all cases. There was no significant difference in blood cell counts, sedimentation rates, incidence of eosinophilia, or guaiac test results between cases and controls. Interestingly, an increased prevalence of Helicobacter pylori was found among cases in this study. Chen et al were not able to demonstrate any associated pathogenicity of B hominis infections.

Murga-Gutierrez and colleagues studied 72 stool samples from children with acute diarrhea and 48 samples from children without diarrhea in the same area of Peru. B hominis was identified in 44% of the samples from children with diarrhea and in significantly fewer children (P < .01) without diarrhea. Though causality was not determined, they concluded that B hominis is at least associated with acute diarrheal disease in children.

In a prevalence survey of 9 communities of Peru reported by Marcos and colleagues, B hominis was found in 30% of individuals tested (aged 1-52 years, mostly children). In Maco and colleagues’ study of young adult male Peruvian military members, however, B hominis was identified in only 1%.

Comment by Muhammad R. Sohail, MD, and Philip R. Fischer, MD, DTM&H

B hominis is a protozoan parasite that is commonly found in the human intestinal tract. As seen in the 4 studies noted above, this parasite is frequently found in individuals both with and without gastrointestinal symptoms, but the prevalence of infection varies among various population groups studied. Since its original description 90 years ago, much controversy has surrounded its taxonomy, diagnosis, and pathogenicity in humans.

B hominis is an obligate anaerobic protozoan with worldwide distribution. In humans, it resides in the colon and cecum. The mode of transmission of B hominis is thought to be via the fecal-oral route. Higher prevalence rates of Blastocystis have been reported from developing countries (30-50%), compared with more developed parts of the world (1-10%). In such areas, travel to tropical regions is a known risk factor for acquisition of B hominis infection, as is the use of untreated water, abnormal gastrointestinal function, and immunosuppression.

In previously published case series where B hominis was presumed to be a pathogen, symptoms attributed to this organism included nausea, anorexia, acute or chronic diarrhea, abdominal pain, cramping, bloating, and fatigue. There are a few case reports of invasive disease attributed to B hominis, including both hemorrhagic procto-colitis and the finding of B hominis in the synovial fluid of a patient with rheumatoid arthritis who was on oral corticosteroids.

The actual pathogenic role of B hominis, however, has been a subject of much controversy. There are some published data to suggest a pathogenic role for B hominis in certain animals. In a murine model, Moe et al infected immunocompetent mice with fecal cysts of B hominis.1 Infection was self-limited, but some mice showed weight loss and lethargy. Histological examination of the cecum and colon showed intense inflammatory-cell infiltrate, edematous lamina propria, and mucosal sloughing. However, no organisms were seen invading the colonic wall. In a study of guinea pigs infected with B hominis, inflammation of intestinal mucosa and invasion of superficial layers were seen. However, no similar histopathologic findings have been reported in case-control studies of humans, including Chen et al’s study as summarized above.

A careful review of published literature suggests that Koch’s postulates have not yet been satisfied, and several factors complicate the establishment of B hominis as a true pathogen in humans. First, some studies suggesting B hominis is a human pathogen, such as that of Murga-Gutierrez et al, are case reports or case series and uncontrolled retrospective reviews. Most studies that include control populations have failed to show a significant difference in B hominis prevalence or symptoms between symptomatic cases and asymptomatic controls. Second, there is a lack of standardized criteria for diagnosis of B hominis infection. In fact, it is conceivable that, similar to Entamoeba species, there may be identically appearing virulent and avirulent strains of B hominis. Also, a carrier or convalescent asymptomatic state might occur, as with Giardia and Cryptosporidium infections. Third, some authors have suggested that host immune status may determine both the presence and severity of symptoms. However, in a detailed study of homosexual men in which B hominis was the most commonly identified enteric parasite,2 there were no differences in either prevalence or symptoms between HIV-positive and HIV-negative individuals. Fourth, any presumed response to treatment may be secondary to the eradication of other concurrently infecting, but undiagnosed, pathogens.

Chen et al’s study is useful in that it found no clinical or endoscopic evidence of pathogenicity in 99 individuals with isolated B hominis infection. In another case-control study, Udkow et al examined fecal smears from 182 asymptomatic controls and 125 symptomatic patients.3 No statistically significant difference in prevalence of B hominis was found between the groups. In addition, the clinical profile of subjects with B hominis and those not infected was similar, and no correlation was found between the presence of B hominis and that of fecal leukocytes. High stool concentrations of B hominis were more frequent, as were other pathogenic protozoa, in symptomatic patients than in those who were asymptomatic, suggesting that presence of B hominis in stools should alert clinicians for possible presence of other, coincident enteric organisms. Similarly, in Chen et al’s study, B hominis enteric colonization was associated with hepatitis B and H pylori infection.

Some authors have suggested that the burden of organisms in stool correlates with symptoms in patients with B hominis infection, but results of several studies have refuted this argument. In a case-control study among expatriates and tourists in Nepal, investigators compared the prevalence of the organism among patients with diarrhea to that among a control group without diarrhea.4 There was no difference in detection rate of B hominis among cases and controls (56 of 189 patients with diarrhea [30%], compared with 40 of 112 asymptomatic controls [36%]). In addition, no correlation was found between higher parasite concentrations and the severity of diarrhea. Other enteric pathogens were detected in 68% of these cases. Results of this study also suggest that, despite the high prevalence of the organism among travelers and expatriates, B hominis does not cause diarrhea in this population, and there is no correlation between organism load and symptoms of infection.

Some studies have suggested that abnormalities of the gastrointestinal system may predispose to colonization and overgrowth of B hominis. Reported gastrointestinal abnormalities in such cases have included intestinal obstruction, malignancy, and irritable bowel syndrome. This suggests that B hominis may be a marker of other functional or organic enteric diseases, and its presence in stools should prompt clinicians to investigate for such causes in appropriate settings.

Without clear evidence for the pathogenicity of B hominis, the treatment of B hominis-positive individuals is also plagued with controversy. Treating children with B hominis correlated with improved resolution of diarrhea in one study and prompted the investigators to speculate that Blastocystis is indeed a human pathogen.5 In HIV-positive patients with bacterial enteritis and either Blastocystis or Cryptosporidium, treatment with rifaximin facilitated clinical recovery and clearance of parasites.6 Similarly, cotrimoxazole treatment of children and adults with Blastocystis and diarrhea led to clinical and parasitologic cure.7 Metronidazole is the drug most frequently used to treat B hominis infection and has been associated with parasite clearance and symptomatic improvement.8 Nonetheless, it is not known whether these agents help patients by clearing the Blastocystis or by eradicating another concurrent, but not identified, infection.

In summary, much remains to be learned about B hominis infections. In fact, a recent comprehensive review referred to B hominis science as "terra incognita."9 However, based on the current state of knowledge, we believe that the pathogenic role of B hominis in humans is not established, and treatment directed at eradication of B hominis is not indicated. The presence of B hominis in stools of patients with gastrointestinal symptoms should prompt clinicians to look for other unrecognized enteric pathogens and noninfectious causes of gastrointestinal symptoms. In the absence of any other defined cause of symptoms, treatment with metronidazole or cotrimoxazole may be offered, keeping in mind that resolution of symptoms may be secondary to elimination of coinfections rather than to the eradication of B hominis.

Dr. Sohail is a Fellow in the Division of Infectious Diseases and Internal Medicine at the Mayo Clinic in Rochester, Minn. Dr. Fischer, Professor of Pediatrics, Department of Pediatric & Adolescent Medicine, Mayo Clinic, Rochester, Minn., is Associate Editor of Travel Medicine Advisor.

References

1. Moe KT, et al. Experimental Blastocystis hominis infection in laboratory mice. Parasitol Res. 1997;83:319-325.

2. Church DL, et al. Absence of an association between enteric parasites in the manifestations and pathogenesis of HIV enteropathy in gay men. Scand J Infect Dis. 1992;24:567-575.

3. Udkow MP, Markell EK. Blastocystis hominis: Prevalence in asymptomatic versus symptomatic hosts. J Infect Dis. 1993;168:242-244.

4. Shlim DR, et al. Is Blastocystis hominis a cause of diarrhea in travelers? A prospective controlled study in Nepal. Clin Infect Dis. 1995;21:97-101.

5. O’Gorman MA, et al. Prevalence and characteristics of Blastocystis hominis infection in children. Clin Pediatr. 1993;32:91-96.

6. Amenta M, et al. Intestinal protozoa in HIV-infected patients: Effect of rifaximin in Cryptosporidium parvum and Blastocystis hominis infections. J Chemother. 1999;11:391-395.

7. Ok UZ, et al. Effect of trimethoprim-sulfamethoxazole in Blastocystis hominis infection. Am J Gastroenterol. 1999;94:3245-3247.

8. Nigro L, et al. A placebo-controlled treatment trial of Blastocystis hominis infection with metronidazole. J Travel Med. 2003;10:128-130.

9. Tan KS, et al. Recent advances in Blastocystis hominis research: Hot spots in terra incognita. Int J Parasitol. 2002;32:789-804.