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.

References:

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 

This Month in Blastocystis Research (OCT 2013)

Thanks to Google Scholar and PubMed feeds I can keep myself relatively up-to-date with emerging Blastocystis data and 'breaking news' in the field.

One of things that have caught my attention recently, is the string of foodborne outbreaks in Sweden, due to Cryptosporidium, Cyclospora and microsporidia stemming from (presumably) imported produce. A few of my colleagues (Robertsen et al., in press) have just published a large review on the impact of globalisation on foodborne parasites - a resource that has been a long time coming, and which I hope will be read and contemplated by many. The review includes a table on parasites isolated from fresh produce (for some reason the Swedish data was not included), and among these is Blastocystis, which was identified in fresh produce from Saudi Arabia (original data published by Al-Binali et al., 2006). Apart from this, hardly any data is out there on Blastocystis in the environment, and we therefore still know very little about potential sources of transmission and how we are exposed.

In Clinical Microbiology and Infection there is a paper out by Mass et al. on detection of intestinal protozoa in paediatric patients with gastrointestinal symptoms by multiplex real-time PCR. Not surprisingly, the study is from The Netherlands, the cradle of real-time PCR-based parasite diagnostics in clinical microbiology. It's a great paper despite all its limitations, but I couldn't figure out which Blastocystis PCR they used for the study, - I think the authors failed to provide a reference for it. Anyway, the authors found 30% of the children colonised by Blastocystis, while Dientamoeba fragilis was found in a staggering 62%, which is more or less equivalent to what we see in Denmark in this type of cohort (please refer to previous blog post on Dientamoeba fragilis). It appeared that symptom resolution was just as common in patients who were treated with different antibiotics as in patients who were not treated, and the authors end up by highlighting the fact that it is still difficult to know whom and when to test for these parasites, and when to treat them.

In Mexico, Sanchez-Aguillon and colleagues have documented a very nice study on parasitic infections in a Mexican HIV/AIDS cohort. Quite a few of the patients had Cryptosporidium, Cyclospora or Cystoisospora, the presence of which was - not surprisingly - associated with diarrhoea. Table 1 in the paper is a bit confusing, but I believe that Blastocystis was found in about 30%; of note, only ST1 and ST3 were found, adding further support to the hypothesis that ST1 and ST3 are common in most parts of the world, while especially ST4 exhibits vast differences in geographic 'affinity'. The authors end their paper by saying

"Other molecular markers for Blastocystis ST should be studied to elucidate the complexity of this heterogeneous genus and its role in human disease."

Let me just add that subtype identification is a valid proxy for intra-generic diversity in Blastocystis, - we have been looking at mitochondrial genomes and found that analyses based on mitochondrial markers and ribosomal genes reveal similar phylogenetic relationships. So, in terms of transmission and epidemiology in general, the subtyping system ('barcoding') is highly applicable and robust. It is true, however, that we need to see if we can identify specific genes potentially responsible for pathogenesis. The Mexican paper can be accessed here.

There's a very nice paper out now from the Swiss Tropical and Public Health Institute and University of Basel on differential diagnoses of common dermatological problems in returning travellers. Blastocystis has been included in the list (in the section on allergic skin reactions/urticaria) together with a plethora of other infectious agents. Lots of informative images there, and the paper has a nice structure.

Despite loads of daily feeds, a lot of papers relevant to Blastocystis research still escape my attention. I realise that there was a paper out in PLoS Genetics in June on Saprolegnia parasitica (an oomocyte parasitising on fish) which appears to be a good and interesting read. Maybe I'll come back to this one!

For me personally, this month in Blastocystis research has been a month of putting together grant proposals - more so now than usual -, many initiatives are being taken, networks are being expanded, and interesting data are accumulating from various projects... I hope to be back with details on some of this soon!

Literature:

Maas L, Dorigo-Zetsma JW, de Groot CJ, Bouter S, Plötz FB, & van Ewijk BE (2013). Detection of intestinal protozoa in paediatric patients with gastrointestinal symptoms by multiplex real-time PCR. Clinical Microbiology and Infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases PMID: 24131443

Fabiola Sanchez-Aguillon, Eduardo Lopez-Escamilla, Francisco Velez-Perez, Williams Arony Martinez-Flores, Patricia Rodriguez-Zulueta, Joel Martinez-Ocaña, Fernando Martinez-Hernandez, Mirza Romero-Valdovinos, Pablo Maravilla (2013). Parasitic infections in a Mexican HIV/AIDS cohort. The Journal of Infection in Developing Countries PMID: 24129632 

Neumayr A, Hatz C, Blum J. In Press. Not be missed! Differential Diagnoses of Common Dermatological Problems in Returning Travellers. Travel Medicine and Infectious Disease. http://dx.doi.org/10.1016/j.tmaid.2013.09.005

Robertson LJ, Sprong H, Ortega YR, van der Giessen JW, Fayer R. In Press. Impact of globalisation on foodborne parasites. Trends in Parasitology  http://dx.doi.org/10.1016/j.pt.2013.09.005