Primecuts – This Week In The Journals

September 26, 2011

By Kevin Hsueh, MD

Faculty Peer Reviewed

Republican presidential candidate Michele Bachmann set the media abuzz two weeks ago when, during a Republican presidential debate, she called the HPV vaccination a “potentially dangerous drug” that could cause a “negative reaction” in little girls.  Her statement infuriated physicians, not only because it was yet another major national figure endorsing the apparently unkillable myth of the mysteriously toxic vaccination, but also in that here was a government figure contradicting the findings of a report just issued on this exact subject by the Institute of Medicine (IOM).  In this issue of Primecuts, we examine the issue of medical disinformation, and how scientific studies often translate poorly into public understanding and confidence in the medical establishment.

The IOM report, titled the Adverse Effects of Vaccines: Evidence and Causality [1] reviewed all the current and historical data related to possible adverse events.  They specifically targeted the MMR, VZV, DTaP, HPV, Influenza, Meningococcus, and Hepatitis (both A and B) vaccinations for review.  Evaluation of each possible adverse event was based upon both the strength of the epidemiological correlation, as well as that of suggestive pathophysiologic studies.  Epidemiologically the only convincingly suggestive correlations they found were between MMR and a slightly increased risk of febrile seizures and transient arthralgias immediately post-vaccination, and a risk of developing oculorespiratory syndrome with the influenza vaccine.  They also found the suggested pathophysiology between administration of live virus vaccines (VZV and MMR) and the possibility of reactivation/disseminated disease in the immunocompromised, and the link between almost all vaccinations with a possibility of anaphylaxis, convincing, though comfortingly there was limited or insufficient epidemiologic data to support either of these possibilities.  The study also once again emphasized the strong negative epidemiologic data refuting the suggested correlations between MMR and autism or type 1 diabetes, the influenza vaccine and bells palsy or asthma exacerbation, and DTaP and type 1 diabetes.  With regards to the HPV vaccine, the IOM report made it clear that, with the possible exception of anaphylaxis, there was no convincing epidemiology, or even case reports, linking the vaccine to any posited adverse events.  Yet despite this and other authoritative reviews, rumors like those endorsed by Bachmann continue to circulate.

Many believe that vaccines are victims of their own success.  This very success is evident in this week’s New England Journal of Medicine, where an article presented by the CDC showed the marked effect the introduction of routine infant rotavirus vaccination has had on childhood healthcare utilization in the U.S.[2]  In this study, the group used the MarketScan Commercial Claims and Encounters database (a nationwide de-identified claims database) to chart “diarrhea-associated health care events” as well as rotavirus vaccination coverage between 2001 and 2009.  They found that by 2008 (two years after introduction of routine vaccination) the mean coverage of infants under 1 had increased to 73% (compared to 88% who had received DTaP), while number of rotavirus coded hospitalizations had dropped from 14 to 4-6 cases per 10,000 person years (a 60-75% rate reduction) for children under 5.  Overall diarrheal hospitalizations in children under the age of 5 dropped somewhere between 25 and 50% (varying upon time of year), though these gains were not so obviously seen in ER and outpatient visits where the only persistent decrease seemed to be in children under the age of 1.

The CDC group estimated that the decrease in healthcare utilization brought about by routine rotavirus vaccination has led to a $278 million cost savings over the two years of the study.  Yet despite this spectacular reduction in harm and cost, there is very little coverage in the lay press.  Ultimately, the absence of an epidemic does not excitement generate.  The medical literature shares in this somewhat skewed perspective, as major journals sometimes eschew caution in the haste to publish new and exciting results.  Possibly the most notorious example of this phenomenon was the Wakefield article published in The Lancet in 1998, which started the entire MMR vaccine controversy, but even more recent examples exist. One of which may be found in the journal Science, which last week printed a partial retraction of a highly publicized 2009 paper suggesting an infectious etiology (the XMRV retrovirus) for chronic fatigue syndrome.[3]  It turns out that samples used in that study were contaminated by exogenous plasmid DNA leading to false positive confirmation of the presence of the XMRV virus [4].  Not only that, but in study released this same week, nine different labs could not replicate the results seen in the initial 2009 paper[5].  In a blinded fashion, these labs used blood samples from some of the same patients used in the initial 2009 study, with the same detection methods (as well as others) to try and identify the presence of XMRV in the samples.  No assay was able to reproducibly detect XMRV in these patients.

Of course, public confidence in medical knowledge is impacted not only when new ideas  turn out to be false, but also when science finds new phenomena that possibly overturn older conventions.  This may be the case with a new study, soon to be published in Emerging Infectious Diseases, linking another species of tick borne spirochete, Borrelia miyamotoi, with a lyme-like syndrome of febrile illness[6].  In the study, 302 patients presenting to a Russian Municipal Hospital for suspected tick-borne illness were screened with PCR assays for both B. miyamotoi and B. burgdorferi,as well as tick borne encephalitic virus.  They then took the patients that only appeared to have B. miyamotoi infection and characterized their symptoms.  B. miyamotoi infections appeared to cause earlier and higher fevers, and were able to cause a relapsing fever syndrome similar to those found in relapsing fever Borrelia infections.  While cure was achieved with standard lyme disease courses of either ceftriaxone or doxycycline, the study authors did note that B. miyamotoi is carried by all species of ixodid ticks that carry B. burgdorferi, with around 15% of North American deer ticks as carriers.  Combined with the fact that it is not currently detected on standard Lyme panels, it does suggest the possibility that some serologically negative cases of “Lyme disease” may in fact be due to this other species of spirochete.

Lastly, there remain questions that even the medical literature has little certainty regarding.  When these questions the lay community, they often result in panic that practicing physicians can do little to assuage, as the data for any conclusions is far from complete.  Take, for example, the current furor over Bisphenol A (BPA).  BPA is a component of polycarbonate and other plastics, and has been known to have estrogenic effects for some time.  Since the mid 2000’s multiple studies have documented concerning findings regarding how BPA can affect development, however almost all these studies have been in animal models.  A recent study published in the Annals of Internal Medicine sheds some additional light on the possible effects of BPA in humans[7].  In this study, 3423 Chinese volunteers from 3 groups (diabetic, impaired fasting glucose, and normal glucose regulation) had their urine and physical characteristics examined.  They could not find a clear association between the various groups and any difference in urinary BPA.  Interestingly, the median urinary level of BPA in these Chinese citizens was markedly lower than that found when studying Americans, making it difficult to use to form conclusions regarding BPA’s effect on people with a greater than fourfold higher exposure.  Ultimately, even with this additional data, very little can be definitively stated on the subject, except perhaps that BPA is still of great interest to the medical and scientific communities.

These studies demonstrate how confounding medical science can be to the general populace.  New information emerges on supposedly well defined diseases like Lyme disease, while previously touted “advances” like the identification of XMRV get quietly removed from the medical literature.  Astounding successes like the rotavirus vaccination get practically no press, while the dangers of BPA are whispered around the water cooler even when experts in the field firmly state there is insufficient data to draw conclusions.  Alexander Pope once wrote that “a little learning is a dangerous thing.”  Never more true has this proverb been than in the internet age where confused pundits like Michele Bachmann may do significant damage with half heard gossip, and where the medical community is left trying to do damage control and pick up the pieces.

Dr. Kevin Hsueh is the Chief Resident in Quality and Safety at the Manhattan VA. 

Peer reviewed by Barbara Porter, MD, Section Editor, Clinical Correlations  

Image courtesy of Wikimedia Commons

References:

[1]Institute of Medicine. Adverse Effects of Vaccines: Evidence and Causality. Washington, D.C.: The National Academies Press, 2011. Web. http://www.iom.edu/Reports/2011/Adverse-Effects-of-Vaccines-Evidence-and-Causality.aspx.

[2] Cortes, J. E.; Curns, A. T.; Tate, J. E.; Cortese, M. M.; Patel, M. M.; Zhou, F. & Parashar, U. D. “Rotavirus Vaccine and Health Care Utilization for Diarrhea in U.S. Children” New England Journal of Medicine, (2011), 365, 1108-1117 http://www.nejm.org/doi/full/10.1056/NEJMoa1000446?query=featured_home   

 [3] Silverman, R. H.; Das Gupta, J.; Lombardi, V. C.; Ruscetti, F. W.; Pfost, M. A.; Hagen, K. S.; Peterson, D. L.; Ruscetti, S. K.; Bagni, R. K.; Petrow-Sadowski, C.; Gold, B.; Dean, M. & Mikovits, J. A. “Partial Retraction” Science, (2011) http://www.sciencemag.org/content/early/2011/09/21/science.1212182.abstract   

 [4] Lombardi, V. C.; Ruscetti, F. W.; Das Gupta, J.; Pfost, M. A.; Hagen, K. S.; Peterson, D. L.; Ruscetti, S. K.; Bagni, R. K.; Petrow-Sadowski, C.; Gold, B.; Dean, M.; Silverman, R. H. & Mikovits, J. A. “Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome” Science, (2009), 326, 585-589 http://www.sciencemag.org/citmgr?gca=sci;326/5952/585 

[5]  Simmons, G.; Glynn, S. A.; Komaroff, A. L.; Mikovits, J. A.; Tobler, L. H.; Hackett, J.; Tang, N.; Switzer, W. M.; Heneine, W.; Hewlett, I. K.; Zhao, J.; Lo, S.-C.; Alter, H. J.; Linnen, J. M.; Gao, K.; Coffin, J. M.; Kearney, M. F.; Ruscetti, F. W.; Pfost, M. A.; Bethel, J.; Kleinman, S.; Holmberg, J. A.; Busch, M. P. & for the Blood XMRV Scientific Research Working Group (SRWG)  Failure to Confirm XMRV/MLVs in the Blood of Patients with Chronic Fatigue Syndrome: A Multi-Laboratory Study Science, (2011) http://www.sciencemag.org/content/early/2011/09/21/science.1213841.abstract  

 [6]  Platonov AE, Karan LS, Kolyasnikova NM, Makhneva NA, Toporkova MG, Maleev VV, et al. “Humans infected with relapsing fever spirochete Borrelia miyamotoi” Russia. Emerg Infect Dis. (2011) Oct [September 26 2011]. http://dx.doi.org/10.3201/eid1710.101474  http://wwwnc.cdc.gov/eid/article/17/10/10-1474_article.htm  

 [7] Ning, G.; Bi, Y.; Wang, T.; Xu, M.; Xu, Y.; Huang, Y.; Li, M.; Li, X.; Wang, W.; Chen, Y.; Wu, Y.; Hou, J.; Song, A.; Liu, Y. & Lai, S. “Relationship of Urinary Bisphenol A Concentration to Risk for Prevalent Type 2 Diabetes in Chinese Adults” Annals of Internal Medicine, (2011), 155, 368-374 http://www.annals.org/content/155/6/368.abstract 

 

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