Friday, October 26, 2012

Video Abstract on Blastocystis Paper on Search for Drug Targets

Please watch this video abstract co-authored by one of my colleagues, Mark van der Giezen, about the search for suitable drug targets in Blastocystis.

The whole paper can be found here.

The "Flagyl" Poll

For some reason the "Flagyl" poll in the right side bar of this blog was reset; the number of votes was approaching 100. The question was

"For those who have received metronidazole (Flagyl or Protostat) treatment for Blastocystis, please indicate whether you experienced no, transient or permanent improvement (or none of the above)"

The interesting thing is that there was a tie between "no improvement" and "transient improvement", and although this poll could have been heavily biased in numerous ways, it is still completely in line with our experience: Many patients report transient alleviation of symptoms, while others have no clinical benefit from Flagyl. Flagyl is an antibiotic targeting a wide range of bacteria and single-celled parasites. It is sometimes successful in terms of eradicating Dientamoeba fragilis, one of the most common parasites in the human intestine, and a parasite which may cause symptoms especially in children (we are currently conducting a randomised control clinical trial at Statens Serum Institut to explore clinical and microbiological effect of metronidazole treatment of children with D. fragilis).

Many people will get diagnosed with Blastocystis without knowing whether they might also be positive for D. fragilis (and vice versa). It is a complex situation, since both parasites are common, they are difficult to detect unless you use PCR or other specialised analyses, and in most labs they are not tested for on a routine basis. And if they happen to be part of the panel of organisms that is tested for, it may be so that insensitive methods are used for their detection, which means that only a fraction of the cases will be detected. So, this is a bit of a conundrum in itself!

So, it's not easy to know what causes the temporary alleviation in some patients. Is it due to parasite recrudescence? Is it due to parasite eradication with subsequent re-infection? And which parasite? Blastocystis? Dientamoeba? Any others? Or, is it due to perturbation of the intestinal flora in a "positive" direction, which is then gradually going back to normal? Placebo effect? There are possibly many more explanations...

However, deep sequencing of faecal samples pre- and post treatment of parasite-positive patients will probably answer many of our questions...

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 PMID: 23091195

Engsbro AL, & Stensvold CR (2012). Blastocystis: to treat or not to treat ... But how? Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 55 (10), 1431-2 PMID: 22893582

Monday, October 8, 2012

Additional Comments on Blastocystis Treatment

I want to thank for the many emails I get! Unfortunately, I cannot respond to each one of them, in part due to time limits, in part since some of them are a bit off my topic or very difficult to answer. However, a few words on Blastocystis treatment (again!), which will hopefully satisfy some of the readers: 

Differences in the reported efficacy (microbiological and clinical cure) of certain drugs or drug combinations may be due to one or more of the following:

1) Actual differences in efficacy due to differences in pharmacokinetics, and -dynamics. Some drugs used for treatment of intestinal parasites are absorbed quickly from the intestine, while others are practically not absorbed at all (but stay in the intestinal lumen). For instance: Metronidazole is absorbed almost 100% in the proximal part of the intestine and may very well fail to reach Blastocystis, which resides is in the large intestine.

2) Different methods are used for evaluating treatment efficacy. If insensitive methods are used, the efficacy of any drug will be overestimated. Culture in combination with PCR is clearly advantageous in terms of evaluating microbiological efficacy since it will detect viable cells (see previous blog posts).

3) Drugs used in Blastocystis treatment may have broad spectrum antibiotic activity (e.g. metronidazole) and thus affect the surrounding microbiota, which again may influence the ability of Blastocystis to continue establishment. Hence indirect drug actions may play a role too. 

Could vegetables contribute to Blastocystis transmission?

4) Diet. What types of food do we eat? I notice that some people undergoing treatment for “blastocystosis” are cautious about eating carbs, for instance, and turn to vegetables only or at least non-carb diets, thinking that by cutting out carbs, they will cut off the "power supply" to Blastocystis. I’m not sure that this approach is very effective and it’s also important to acknowledge that the processing and metabolism of the foods that we ingest are complex. I hope to be able to do a blog post once on short-chain fatty acids, for instance. Again, changes in our diets may influence our bacterial flora which again may have an impact on Blastocystis. Importantly, we don’t know much about potential transmission of Blastocystis from raw vegetables and whether this could be a potential source infection (vegetables contaminated with Blastocystis).

5) Which leads to the next issue: The issue of re-infection. With so many people infected by Blastocystis (probably between 1-2 b people) it is likely that many of us are often exposed to the parasite. If we receive treatment but are not cut off from the source of infection, microbiological and clinical cure will be short-lived if at all possible.

6) Compliance - some drugs have serious adverse effects, and so, failure to reach microbiological cure may stem from failure to comply with drug prescriptions.

7) Differences in drug susceptibility. There is evidence from in vitro studies that Blastocystis subtypes exhibit differences in drug susceptibility.

In the absence of sound data that take all of the above factors into account, it is not possible for me (or anyone) to predict exactly which drug (combo) that will work and which will not. I think that it is important that GPs or specialists who take an interest in treating Blastocystis collaborate with diagnostic labs that are experts on Blastocystis diagnostics. If any drug or drug combo enabling microbiological cure can be identified, such pilot data can be used to design randomised controlled treatment studies that again will assist us in identifying whether Blastocystis eradication leads to clinical improvement.

I will try and provide some thougths on other future directions for Blastocystis research soon. Stay tuned!