Showing posts with label allele. Show all posts
Showing posts with label allele. Show all posts

Tuesday, March 1, 2016

This Month in Blastocystis Research (FEB 2016) - Rash Edition

A couple of years ago, I contributed to writing up a Case Report on what appeared to be Blastocystis-associated urticaria (hives). Receiving various courses of ineffective antibiotic treatment with a view to eradicating Blastocystis, a woman continued to suffer from gastrointestinal symptoms and generalized urticaria. Only when the infection was eventually successfully eradicated using a combination of metronidazole and paromomycin, the women experienced symptom resolution.

There is a systematic review out just now in the well-esteemed journal "Allergy" on chronic spontaneous urticaria in patients with intestinal parasites. The approach is useful, interesting, and relevant. One of the main results, which was also highlighted in the abstract, is that patients with chronic urticaria more frequently have "Blastocystis hominis allele 34 (ST3)". This observation, however, pertains to one single study, and should be interpreted in this context. The original study was carried out by Rudolfo Daniel Casero and last-authored by a close colleague of mine, Juan David Ramirez, who currently does a lot to promote and improve molecular parasitology research in Latin America; among other things, he's a very successful and avid arranger of workshops. Anyway, the study included observations on Blastocystis in a group of Argentinean patients, who were stratified by the presence or absence of symptoms. Hence, there were four groups, reflecting 1) asymptomatic patients, 2) patients with chronic urticaria, 3) patients with non-specific gastrointestinal symptoms (NSGI), and 4) patients with both chronic urticaria and NSGI. No specific subtype was linked to any of the four groups; however, a very striking observation related to the distribution of ST3 strains across the groups: out of a total of 21 patients positive for ST3 allele 34 (the allele number is used to provide "genotype" information of the subtype), 18 had urticaria. On the other hand, out of 28 patients positive for ST3 allele 134, only 3 had urticaria.

ST3 allele 34 is probably the most common Blastocystis strain overall in many European countries; also in Asia (e.g. India), this genotype particularly common. Although common in South America too, it might not be the most common strain, given the data by Casero et al. These authors are the first to provide a clear association between a Blastocystis strain (i.e., on genotype level) and development of symptoms. Although the data warrant confirmation by prospective studies, the data should be food for thought.

About 20 papers are listed in PubMed on "Blastocystis AND urticaria". Last year, I was so fortunate to host Małgorzata Lepczynska in our lab for a couple of weeks. Incidentally, a review of the role of Blastocystis in the development of urticaria and first-authored by Lepczynska just emerged in PubMed. The authors try to explain the potential mecanisms underlying the development of Blastocystis-induced urticaria. For some reason, the authors did not include a study by Armentia et al. from 1993 (maybe due to the possibility that they had no access the paper?). Armentia presented a case series (n = 10) of Blastocystis patients who all had chronic urticaria; both the parasite and the symptom disappeared upon treatment with paromomycin sulfate.

I am not sure that the data available at this point are sufficient to generate inferences on the contributing role of Blastocystis in the development of urticaria; however, I would not hesitate to encourage dermatologists to look into the issues of "idiopathic chronic urticaria", with a view to clarifying the rate of Blastocystis colonisation among these patients and whether parasite eradication leads to symptom resolution. Such studies should also involve total analysis of the intestinal microbiota, both before and after treatment.


Armentia A, Méndez J, Gómez A, Sanchís E, Fernández A, de la Fuente R, & Sánchez P (1993). Urticaria by Blastocystis hominis. Successful treatment with paromomycin. Allergologia et Immunopathologia, 21 (4), 149-51 PMID: 8237719   

Casero, R., Mongi, F., Sánchez, A., & Ramírez, J. (2015). Blastocystis and urticaria: Examination of subtypes and morphotypes in an unusual clinical manifestation Acta Tropica, 148, 156-161 DOI: 10.1016/j.actatropica.2015.05.004

Kolkhir P, Balakirski G, Merk HF, Olisova O, & Maurer M (2016). Chronic spontaneous urticaria and internal parasites - a systematic review. Allergy, 71 (3), 308-22 PMID: 26648083

Lepczyńska M, Chen WC, & Dzika E (2016). Mysterious chronic urticaria caused by Blastocystis spp.? International Journal of Dermatology, 55 (3), 259-66 PMID: 26469206 

Vogelberg C, Stensvold CR, Monecke S, Ditzen A, Stopsack K, Heinrich-Gräfe U, & Pöhlmann C (2010). Blastocystis sp. subtype 2 detection during recurrence of gastrointestinal and urticarial symptoms. Parasitology International, 59 (3), 469-71 PMID: 20363362 

Wednesday, May 2, 2012

Blastocystis Sequence Typing Home Page

Last year, we launched the Blastocystis Sequence Typing Home Page, which is a publicly accessible resource including two major facilities: 1) A sequence database and 2) An isolate database.
The databases cover both SSU-rDNA data and Multilocus Sequence Typing (MLST) data. For those interested in MLST, please visit this paper.The rest of this post will be about SSU-rDNA sequences.

The database has a BLAST function. Barcoding sequences (i.e. sequences which include the 500 5'-most bases in the SSU-rDNA) can be submitted individually or in bulks, and the output file will include information on subtype (ST) and allele. The number of alleles in ST3 is huge (currently n=38) compared to other subtypes, for which only 2-3 alleles have been identified (e.g. ST8). In case a sequence is submitted that is not similar to an allele already present in the database, I suggest that you do an individual sequence query, which enables the generation of an alignment, which will show you the polymorphism(s). In case a new allele is identified, I suggest that we submit this new allele to the sequence database.
We not only strongly encourage using this BLAST feature for quick and standardised subtype and allele identification, but also for submitting isolate data, i.e. barcode sequences with provenance data (data on host, symptoms, geographical origin, etc.); again this can be done by contacting the curator (me); please look up the site for more information.

Our goal is to produce a database which accommodates large sets of data that can be submitted to scrutiny by everyone. The isolate database currently holds almost 700 isolates with 118 unique alleles - I hope this can be expanded much, much more. Also, data extracts can be done at all times, and below is a random example of an extract from human and non-human data from France downloaded from GenBank:
The colours indicate different alleles in different hosts (see legend to the right). A file with all alleles in fasta format is available here. You can paste them into the search field here for a total list of alleles currently in the database; try clicking on a couple to familiarise yourself with the system... One of the things that we can see here is that alleles 34, 36, 37 (ST3) and allele 4 (ST1) are the most common alleles in humans in France. It may seem a bit confusing to speak of both subtypes AND alleles. However, alleles are a good proxy for MLST data, and hence, looking at alleles is useful, e.g. in terms of transmission studies.

There are many other ways of extracting and visualising data from the isolate database. For more information on barcoding, subtypes, alleles, and the databases, please do not hesitate to contact me. I emphasise that the database only works with sequences that include the barcode region; mutliple SSU-rDNA targets have been used for subtyping, but due to the fact that this database is based on barcode data, we recommend that subtyping be done by barcoding (see references).

Useful literature:

Stensvold, C., Alfellani, M., & Clark, C. (2012). Levels of genetic diversity vary dramatically between Blastocystis subtypes Infection, Genetics and Evolution, 12 (2), 263-273 DOI: 10.1016/j.meegid.2011.11.002  

Scicluna SM, Tawari B, & Clark CG (2006). DNA barcoding of Blastocystis. Protist, 157 (1), 77-85 PMID: 16431158