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Tuesday, May 27, 2008

The Swedish Chlamydia Mystery

ResearchBlogging.org

Authors: Nils Reinton and Amir Moghaddam
Furst Medical Laboratory, Søren Bullsv. 25, N-1051 Oslo, Norway (nreinton_at_furst.no)

In 2006, Swedish researchers noticed a peculiar trend in the number of positive Chlamydia trachomatis cases. The number of infected patients was down by as much as 25 %. This was unexpected since there had been no public health (or preventive medical) actions to explain such a drastic decrease. Also, the numbers tested for C.trachomatis was similar to previous years. In addition, this trend had not been observed anywhere else. Something strange was happening to sexually active individuals in Sweden in particular.

The reason they found, was not due to calculation error or changes in sexual habits, but in molecular diagnostics, or more precisely, the genetic flexibility of
C.trachomatis (1). A genetic change had appeared creating a novel strain that was given the name "nvC.trachomatis.". This strain had a deletion in its "cryptic plasmid". The deletion was situated in the middle of the target sequence used by diagnostic kits from Abbott and Roche. Consequently, labs using kits from these suppliers (almost everyone in Sweden were using Roche) would misdiagnose any patient infected with the variant as negative for C.trachomatis infection. As a consequence of a diagnostics driven selection pressure, nvC.trachomatis may have reached almost 40 % of total C.trachomatis infections in Sweden (2). Numbers as high as 78 % were reported in some Swedish counties (3). Rapidly then, new tests were introduced to detect the strain and subsequent changes of laboratory routines in Sweden restored normal C.trachomatis detection specificities. Thus, the problem was fixed and everyone thought the mystery was solved.

Not so it seems. The real mystery started when neighboring countries started looking for the variant. Since there is extensive traveling and exchange of labor between the Nordic countries it would seem only natural that the variant C.trachomatis should spread rapidly to other countries as well. Curiously, that did not happen. By now, there have been studies in Norway (4), Denmark (5), England and Wales (6), Ireland (7) and the Netherlands (8). The only other countries nvC.trachomatis was detected was Norway where two out of 47 positives had the variant (one of these was a Swedish citizen) and Denmark which had only two cases out of a total of 383 positives. The conclusion from S Hoffmann and JS Jensen (reference 5) summed it up nicely:
"Sexually transmitted infections are unlikely to respect national borders, especially in an extended period of time. It was therefore an unexpected finding that only one case of the new CT variant was detected among 3,770 specimens tested during a five-month period. The samples were submitted from the whole of Denmark, although the majority came from the Copenhagen area. Considering the intense daily traffic between the Copenhagen area in Denmark and southern parts of Sweden, it is surprising that the spread occurred so late."
The spread is still limited. So far (April 2008) other labs in Norway have failed to find any cases at all, while our laboratory (in Oslo Norway, doing more than 20 000 C.trachomatis analyses a year) only rarely have cases of nvC.trachomatis infection. Consequently, by large the nvC.trachomatis strain remains Sweden-specific. A bug that is specific for only one given nationality is surely a novelty in epidemiology.

Finding the reason seems be far off at the moment. Because: is it likely that Swedes have strong sexual preferences towards other Swedes only ? Or are there biological differences that makes Swedes more prone to nv
C.trachomatis infection ? Sexual behavior and biological signature-attributes either in the infectious agent or in the host, are usually the starting points for STD epidemiology. But in this case either scenario is unlikely. So far then, the mystery remains unsolved.

The lesson learned in diagnostics however, was probably useful for future development of diagnostic tests as pointed out by Björn Hermann (reference
3):
"What can we learn from the emergence of this new variant of chlamydia? This thrilling story provides several lessons. Firstly, how to design a diagnostic test. The new variant is a striking example of diagnostics driven evolution that must be considered when new methods are designed. Since routine diagnostics for chlamydia uses high volume testing based on nucleic acid detection, it is important that the targets used are not only conserved genetic elements but also essential for the organism."
Also, comfort can be taken in knowing that the variant C.trachomatis has lost its evolutionary advantage since due to these events, diagnostics manufacturers have changed their kits to be able to detect all known variants of C.trachomatis. And, in addition, one can hope that through this curious epidemiology event, awareness of STDs have been raised further.

Constant awareness is surely needed given the continuous rise in positive
C.trachomatis cases (regardless of variant strains). Unfortunately, a growing number of C.trachomatis-cases raises the probability of other new strains emerging through natural selection. This time it was easy to adapt to the new situation by changing the diagnostic method. The next time a variant bug appears it may not be this easy to find a fix. Treating the bug and stopping its spread (to achieve eradication) is what we should aim for. This story is just another one of the many wake-up calls given to us in the fight against disease-causing microorganisms over the recent years.

Reinton, N., Moghaddam, A.The Swedish Chlamydia Mystery. Sciphu.com

4 comments:

Scott Eaker said...

I wonder weather there is a difference in the use of the Abbott and Roche kits between the countries? Is there less use of these kits for diagnosis and more symptomatic diagnosis of Chlamydia infection?

SciPhu said...

Yes you are absolutely right. In Sweden they were using Abbott and Roche kits almost exclusively and this is probably the reason the mutant spread so rapidly in this country. In Norway the C. trachomatis market is divided between Becton Dickinson (BD) and Roche. The BD kits picks up the mutant and this is probably the reason why the mutant has not outcompeted other strains in Norway. I do not have information on the dominating diagnostic methods in other European countries. But, even if this does explain the explosion of the mutant strain in Sweden, and the lack of such an explosion in Norway, the mystery that the mutant hasn't crossed the Swedish borders to a larger extent still remains. Nils Reinton

Anonymous said...

I have wondered at this possibility for some time. How close genetically are the neighboring countries? If someone with the data can run the math and analyses a specific genetic resistence or vulnerability thourgh a specific difference might be detected. Nasty possibilites if anyone is motivated to target specific populations deliberately and has enough knowledge, access, etc. or for profit motives are a possibililty. Keep up the good work. Referring this on to others

SciPhu said...

The neighboring countries in this case, are very similar both culturally and in terms of genetics. It is therefore highly unlikely that the containment in Sweden was caused by genetic resistance in Norway or Denmark. This is also mentioned in the article (section 6, last two sentences). Although not an expert on biological warfare or similar issues, I strongly believe that the fear of production of population-specific modified microorganisms for hostile purposes is unwarranted. One would think also that C. trachomatis is unsuitable as a biological weapon, and finally, C. trachomatis is probably not a candidate for illegal commercial exploitation since it is widespread across the globe already.