Blastocystis: To Treat or Not to Treat … But How? TO THE EDITOR—In their recent paper, Coyle et al [1] recommend metronidazole as the drug of choice for Blastocystis eradication. We have come across multiple cases where high-dose metronidazole treatment does not eliminate Blastocystis from the intestine. In fact, it appears that no single drug is capable of eradicating Blastocystis [2].
Here, we present an example of an intractable Blastocystis infection despite multiple courses of antibiotic intervention. A 36-year-old female presented with a 9-month history of abdominal pain, diarrhea, and bloating. Blood tests and a sigmoidoscopy with biopsies were normal, and she was diagnosed with irritable bowel syndrome (IBS) according to Rome III criteria [3]. Fecal samples revealed Blastocystis sp. subtype 9 (ST9) and Dientamoeba fragilis. During a period of almost 3 years, she sequentially received antimicrobial treatment (Table 1). Clinical and microbiological effect was systematically evaluated 2 weeks after treatment. Although the patient was cleared of D. fragilis, none of these treatments successfully eliminated Blastocystis ST9, which was repeatedly isolated from her feces, nor did they alleviate her gastrointestinal symptoms. No further treatment options are available in general in Denmark. The mechanisms leading to Blastocystis eradication are unclear. Using molecular diagnostics, we have come to realize that the parasite colonizes a substantial proportion of any given population [4]. With such a high rate of colonization, we must anticipate that we are all exposed to Blastocystis regularly, and therefore the factors influencing successful Blastocystis colonization should be explored [4]. Metagenomic studies have led to advances in the understanding of the structure and function of the human intestinal microbiome [5, 6], whereas nonprokaryotic organisms remain much less studied. If Blastocystis colonization is dependent on the composition of the bacterial flora as suggested recently [4], it is striking that the parasite could be sustained throughout the many different courses of antimicrobial treatment in this IBS patient. Eradication of Blastocystis may happen directly ( protistostatic or protistocidal effect) or indirectly (due to perturbations of the intestinal flora). In this case eradication failed, and our study adds to the string of papers
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Table 1. List of Trials of Antimicrobial Treatment in a Danish Patient With Irritable Bowel Syndrome Harboring Blastocystis Sp. Subtype 9 and Dientamoeba Fragilis
Agent(s)
Dosage
Clinical Effect
Microbiological Effect
MZ
750 mg thrice daily/10 days
None
None
Tetracycline
500 mg 4 times daily/10 days
None
None
TMP/SXT
TMP 800 mg/SXT 160 mg twice daily/7 days
None
None
MB + MZ
MB 100 mg thrice separated by 2 weeks, followed by MZ 750 mg thrice daily/10 days
None
None
PM + MZ
PM 500 mg + MZ 750 mg thrice daily/10 days
None
D. fragilis eradicated
Abbreviations: MB, mebendazole; MZ, metronidazole; PM, paromomycin; SXT, sulfamethoxazole; TMP, trimethoprim.
suggesting that metronidazole does not result in Blastocystis eradication [2]. This means that Blastocystis may be unsusceptible to agents normally used to treat amoebic infections and that Blastocystis might possess the ability to adapt to rapid changes in gut microbiome ecology. Future studies should aim at exploring potential differences in the microbiome structure of individuals with and without Blastocystis and monitor the microbial changes during treatment by methods such as metagenomics or denaturing gel gradient electrophoresis, and to try to obtain a mechanistic understanding of Blastocystis eradication. It is clear that eradication of some microeukaryotes from the intestinal lumen remains extremely challenging, if possible at all, which certainly complicates the design of randomized controlled treatment studies that could shed further light on the clinical role of Blastocystis. However, the Blastocystis genome is now available [7], and analysis of metabolic pathways and protein homology modeling will assist us in identifying relevant targets for targeted chemotherapeutic intervention. Notes Financial support. This work was supported by the Danish Council for Independent Research, Medical Sciences, Ministry of Science, Technology and Innovation; Region Zealands Health Sciences Research Foundation; and the
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Council for Quality Assurance in Primary Care, Region Zealand, Denmark (to A. L. E.). Potential conflicts of interest. Both authors: No reported conflicts. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Anne Line Engsbro1,2 and Christen Rune Stensvold3 Department of Medicine, Køge Hospital, 2University of Copenhagen, and 3Laboratory of Parasitology, Department of Microbiological Diagnostics, Statens Serum Institut, Copenhagen, Denmark
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References 1. Coyle CM, Varughese J, Weiss LM, Tanowitz HB. Blastocystis: to treat or not to treat … . Clin Infect Dis 2012; 54:105–10. 2. Stensvold CR, Smith HV, Nagel R, Olsen KE, Traub RJ. Eradication of Blastocystis carriage with antimicrobials: reality or delusion? J Clin Gastroenterol 2010; 44:85–90. 3. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology 2006; 130:1480–91. 4. Stensvold CR. Thinking Blastocystis out of the box. Trends Parasitol 2012; 28:305. 5. Structure, function and diversity of the healthy human microbiome. Nature 2012; 486:207–14. 6. A framework for human microbiome research. Nature 2012; 486:215–21. 7. Denoeud F, Roussel M, Noel B, et al. Genome sequence of the stramenopile Blastocystis, a human anaerobic parasite. Genome Biol 2011; 12:R29. Correspondence: Anne Line Engsbro MD, PhD, Department of Medicine, Køge Hospital, Lykkebækvej 1, 4600 Køge, Denmark (
[email protected]).
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Clinical Infectious Diseases 2012;55(10):1431–2 © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.
[email protected]. DOI: 10.1093/cid/cis699
