Showing posts with label differential diagnosis. Show all posts
Showing posts with label differential diagnosis. Show all posts

Friday, April 1, 2016

This Month in Blastocystis Research (MAR 2016)

I'm going to dedicate this post entirely to a recent case presented by my wonderful colleague Bobbi Pritt (Mayo Clinic) in collaboration with Blaine Mathison (CDC), whom I have also been so fortunate to meet.

Please go here to see the case.

Creepy Dreadful Wonderful Parasites: Case of the Week 390.

Let me use the opportunity to congratulate Bobbi Pritt on her fantastic work, admirable skills, and dedication to parasitology!

And by the way; why not treat yourself to Bobbi's 2016 parasite calendar available for purchase here.

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, October 16, 2013

Dying to know about Dientamoeba?

It's difficult to say 'Blastocystis' without saying 'Dientamoeba fragilis'. Both parasites tend to be extremely common in countries where other intestinal parasites (e.g. Entamoeba, Giardia, Cryptosporidium) are of low endemic occurrence, and they are often seen together in patient samples. It is only due to the recent introduction of DNA-based diagnostic methods (PCR) that we now know that these parasites are much more common than previously anticipated.

So, while I'm trying to encourage guest bloggers, I thought I'd introduce a 'guest star' - Dientamoeba!

Dientamoeba fragilis trophozoites with the characteristic binucleated feature.
The parasite belongs to the trichomonads, which also comprise parasites such as Histomonas meleagridis (the cause of 'blackhead disease' in turkeys) and - more distantly - Trichomonas vaginalis.

At our Parasitology Lab at Statens Serum Institut in Copenhagen we have been using real-time PCR for specific detection of Dientamoeba fragilis in faecal samples from patients with gastrointestinal symptoms for quite a few years now. In the period of 2008-2011 we analysed 22,484 stool samples for D. fragilis. The overall prevalence of the parasite in these samples was 43% but depended mainly on age (Figure 1). D. fragilis prevalence appears to fluctuate dramatically depending on the age group. Highest prevalence was seen among 7-year-olds, and a second 'peak' is seen in the parental age suggesting that infected children pass on infections to their parents. 

Figure 1:  Prevalence of D. fragilis as a function of age. (For more information, see Röser et al., 2013b).

Intestinal protozoa are transmitted faecal-orally and most of them have a cyst stage. However, a few protozoa appear not to have a cyst stage, among them D. fragilis. There is a lot of evidence that Histomonas meleagridis is transmitted by eggs of Heterakis gallinae, a nematode of galliform birds. Conspicuously, we recently demonstrated the presence of D. fragilis DNA in surface-sterilised eggs of Enterobius vermicularis (pinworm). The implications of this finding are unclear but could suggest a similar vector-borne transmission of D. fragilis.

As in so many other situations it is not possible to dish out simple guidelines as to when to test for and treat D. fragilis. It is clear that many carriers experience few or no symptoms at all, but there are several case reports demonstrating symptom relief in patients eradicated of D. fragilis. We published one such case recently in 'Ugeskrift for Læger' - the journal of the Danish Medical Association. Basically, the report describes lasting symptom relief after documented eradication of D. fragilis using high dose metronidazole. However, the patient's symptoms returned after a year, and  real-time PCR revealed D. fragilis positive stools. Eradication was achieved using paromomycin (250 mg x 3 for nine days).

Contrary to Blastocystis, this parasite exhibits remarkably limited genetic diversity. We recently analysed three different genetic loci (18S, actin, elongation factor 1-alpha), and we confirmed that only 2 genotypes exist, one of which is very rare. Genetically, however, the two genotypes are quite different, and it will be interesting to compare the nuclear genomes of the two, once they have become available.

Dientamoeba has been speculated to be a neglected cause/differential diagnosis of irritable bowel syndrome (IBS). We once found a statistical significant association between IBS and Dientamoeba; however, other more recent and more targeted studies (one of which is ongoing) have not confirmed this association. However, multiple factors could interact and analysing only simple associations such as symptoms related to parasite presence/absence may be a limiting approach; for instance, infection load/intensity may play a role, and other factors such as host genetics/susceptibility and microbiota ecology may be significant factors influencing on clinical outcome as well. On that note, we have observed some very low Ct values in our real-time PCR results for some of our D. fragilis positive patients, suggesting massive infections. D. fragilis infections are probably often long lasting (months), and if symptoms appear in the initial phase of infection only, cross-sectional studies of prevalence and clinical presentation will be potentially misleading. Large longitudinal cohort studies of pre-school children with monitoring of incidence of pinworm and D. fragilis infections would be extremely informative.

Dr Dennis Röser here at the SSI is currently finishing a randomised controlled treatment trial of D. fragilis in children, testing the clinical efficacy of metronidazole treatment versus placebo. Results are expected next year, so watch out for a 'D. fragilis special' by Dr Röser in 2014! It appears a lot easier to eradicate D. fragilis than Blastocystis - at least on a short term basis with metronidazole having an efficacy of about 70% or so (unconfirmed).

A couple of reviews free for download are available; please see literature list below or go here and here.

Suggested literature

Engsbro AL, Stensvold CR, Nielsen HV, & Bytzer P (2012). Treatment of Dientamoeba fragilis in patients with irritable bowel syndrome. The American Journal of Tropical Medicine and Hygiene, 87 (6), 1046-52 PMID: 23091195   

Johnson EH, Windsor JJ, & Clark CG (2004). Emerging from obscurity: biological, clinical, and diagnostic aspects of Dientamoeba fragilis. Clinical Microbiology Reviews, 17 (3) PMID: 15258093

Ogren J, Dienus O, Löfgren S, Iveroth P, & Matussek A (2013). Dientamoeba fragilis DNA detection in Enterobius vermicularis eggs. Pathogens and Disease PMID: 23893951  

Röser D, Nejsum P, Carlsgart AJ, Nielsen HV, & Stensvold CR (2013a). DNA of Dientamoeba fragilis detected within surface-sterilized eggs of Enterobius vermicularis. Experimental Parasitology, 133 (1), 57-61 PMID: 23116599   

Röser D, Simonsen J, Nielsen HV, Stensvold CR, & Mølbak K (2013b). Dientamoeba fragilis in Denmark: epidemiological experience derived from four years of routine real-time PCR. European Journal of Clinical Microbiology & Infectious Diseases : official publication of the European Society of Clinical Microbiology, 32 (10), 1303-10 PMID: 23609513  

Stark DJ, Beebe N, Marriott D, Ellis JT, & Harkness J (2006). Dientamoebiasis: clinical importance and recent advances. Trends in Parasitology, 22 (2), 92-6 PMID: 16380293  

Stark D, Barratt J, Roberts T, Marriott D, Harkness J, & Ellis J (2010). A review of the clinical presentation of dientamoebiasis. The American Journal of Tropical Medicine and Hygiene, 82 (4), 614-9 PMID: 20348509

Stensvold CR, Clark CG, & Röser D (2013). Limited intra-genetic diversity in Dientamoeba fragilis housekeeping genes. Infection, Genetics and Evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 18, 284-6 PMID: 23681023

Stensvold CR, Lewis HC, Hammerum AM, Porsbo LJ, Nielsen SS, Olsen KE, Arendrup MC, Nielsen HV, & Mølbak K (2009). Blastocystis: unravelling potential risk factors and clinical significance of a common but neglected parasite. Epidemiology and infection, 137 (11), 1655-63 PMID: 19393117