Archive for the ‘Scientific Evidence’ Category

Journal Club Debunks Anti-Vaccine Myths

November 2, 2010 2 comments


American Family Physician, the journal of the American Academy of Family Physicians, has a feature called AFP Journal Club, where physicians analyze a journal article that either involves a hot topic affecting family physicians or busts a commonly held medical myth. In the September 15, 2010 issue they discussed “Vaccines and autism: a tale of shifting hypotheses,” by Gerber and Offit, published in Clinical Infectious Diseasesin 2009.

The article presented convincing evidence to debunk 3 myths:

  1. MMR causes autism.
  2. Thimerosal (mercury) causes autism.
  3. Simultaneous administration of multiple vaccines overwhelms and weakens the immune system, triggering autism in a susceptible host.

Gerber and Offit reviewed 13 large-scale studies that demonstrated no association between the MMR vaccine and autism. These included ecologic studies, retrospective observational studies and prospective observational studies.  The findings were consistent; the only outlier in all the studies of MMR was Dr. Andrew Wakefield’s small, discredited 1998 study, which was fully retracted by The Lancet in early 2010.

They reviewed 7 large-scale studies (again, ecologic, retrospective, and prospective) that consistently demonstrated no association between thimerosal and autism. They showed that the hypothesis was not biologically plausible, since the symptoms of mercury poisoning are distinct from those of autism and are not produced by the thimerosal in vaccines.

They showed that the overload hypothesis is not credible because

  1. The immunologic load has dropped from 3000 components in the 7 vaccines used in 1980 to less than 200 in the 14 vaccines recommended today.
  2. An infant’s immune system is capable of handling the thousands of antigens it is exposed to early in life.
  3. Vaccinated children are not more susceptible to infections.
  4. Autism is not an autoimmune disease.





New bivalent polio vaccine performs better than trivalent and just as well as monovalent vaccines

October 28, 2010 Leave a comment

A new study, published online at The Lancet shows that the bivalent polio vaccine, which is currently in use in India and Nigeria and offers protection against two of the polio virus strains, type 1 & 3, triggers a stronger immune response than the existing trivalent vaccine and similar immune response to the monovalent vaccines.

Immunogenicity of bivalent types 1 and 3 oral poliovirus vaccine: a randomised, double-blind, controlled trial

Dr Roland W Sutter MD a , Prof T Jacob John FRCP[E] b, Prof Hemant Jain MD c, Prof Sharad Agarkhedkar MD d, Prof Padmasini Venkat Ramanan MD e, Harish Verma MB f, Jagadish Deshpande PhD g, Ajit Pal Singh MB h, Meghana Sreevatsava MPH a, Pradeep Malankar MD a, Anthony Burton a, Arani Chatterjee MB h, Hamid Jafari MD f, R Bruce Aylward MD a

Study Summary – This was a double-blind, randomized,  controlled study which enrolled 830 babies in India, between August and December 2008. The researchers compared various oral polio vaccines’ efficacy in inducing an immune response, measured by the number of antibodies created after the doses were received (seroconversion). The total amount of antibodies was measured and compared after the first dose, and also after a second dose.

The babies were set up in 5 groups; it is not clear from the summary but it appears that each group would have received one of the following vaccines:

  • monovalent type 1
  • monovalent type 2
  • monovalent type 3
  • bivalent 1 & 3
  • trivalent.

Although it is possible that some group may have been given a combination of monovalent vaccines; I am not sure. What does mono, bi, trivalent mean? It means this: the monovalent vaccines protect against one type only of the virus that causes polio. For example, monovalent type 1 protects against the Type 1 of the polio virus. Bivalent vaccines protect against two types at the same time, and trivalent vaccine protects against 3 types at the same time.

Immune response, or seroconversion, was measured after the first dose, and after the second dose of the vaccines. The responses were compared for the various vaccines.

Results – The results were as such:

Seroconversion after Dose 1

Type 1 Virus

  • Monovalent  – 20%
  • Bivalent – 20%
  • Trivalent – 15%

Type 2 Virus

  • Monovalent – 21%
  • Bivalent – N/A
  • Trivalent – 25%

Type 3 Virus

  • Monovalent – 12%
  • Bivalent – 7%
  • Trivalent – 4%

Seroconversion after Dose 2 (cumulative)

Type 1 Virus

  • Monovalent – 90%
  • Bivalent – 86%
  • Trivalent – 63%

Type 2 Virus

  • Monovalent – 90%
  • Bivalent – N/A
  • Trivalent – 91%

Type 3 Virus

  • Monovalent – 84%
  • Bivalent – 74%
  • Trivalent – 52%

The vaccines were well tolerated. 19 serious adverse events occurred, including one death; however, these events were not attributed to the trial interventions.

Conclusion – This study shows statistically significant differences between the bivalent and the trivalent vaccine, differences that become clearer after the second dose, at which point the bivalent vaccine outscored the trivalent one by more than 20% points for both polio viruses Type 1 and 2. There are no statistically significant differences between the bivalent and monovalent vaccines.

The conclusion following the results of this study is that, in this study the bivalent vaccine worked better than the trivalent vaccine in inducing an immune response, in infants. Further, the bivalent vaccine rates of seroconversion was just as good as the monovalent vaccines ones.

It is important to keep in mind though, that this study was only measuring the immune response, and does not draw any conclusions about the reduction of polio infections, hospitalizations or death rates. If that was the goal of the study, a proper placebo control would be absolutely necessary, but given that the purpose of the study was to compare efficacy of seroconversion rates as compared to the trivalent/monovalent vaccines, the use of a placebo is not necessary, since it is logical to assume that any placebo effects would similarly affect all groups of participants.

As such this study, in and off itself, does not lead to any conclusions about the bivalent vaccine’s efficacy in preventing polio infections, hospitalizations and deaths. We may extrapolate given it’s seroconversion rates, and what it is known about the monovalent/trivalent vaccines effects on polio infections/hospitalizations/death rates, but that would be just that, an extrapolation. The only question this study directly answers is: How does the bivalent polio vaccine compare to the monovalent and trivalent polio vaccines in inducing an immune response?

The authors concluded as such:

The findings show the superiority of bOPV compared with tOPV, and the non-inferiority of bOPV compared with mOPV1 and mOPV3.

Categories: Efficacy, Polio Tags: ,

Safety of influenza vaccine during pregnancy

October 7, 2010 Leave a comment

Today we will look at the recent recommendation by the CDC, the American College of Obstetricians and Gynecologists,  that, all people over 6 months of age, including pregnant women receive the flu vaccine. Anti-vaccination groups have already come out,  insinuating that the safety of the flu vaccine given during a woman’s pregnancy has not been established. Is that true? Are there any studies that have looked at the safety of the influenza vaccine for pregnant women? The answer is yes, at the very least there is one that I was able to find, using simply Google.

Safety of influenza vaccination during pregnancy.

Munoz FM, Greisinger AJ, Wehmanen OA, Mouzoon ME, Hoyle JC, Smith FA, Glezen WP.

Study Summary – The objective of the study was to “evaluate the safety of influenza vaccine that is administered in the second or third trimester of gestation”. A retrospective electronic database search of 5 influenza seasons (July 1, 1998, to June 30, 2003) was performed at a large multispecialty clinic in Houston, Texas. Immunization rates were calculated, and outcomes of pregnancy were compared between healthy women who received influenza vaccine, and a control group of healthy unvaccinated women who were matched by age, month of delivery, and type of medical insurance.

Results – Among 7183 eligible mother-infant pairs, only 252 pregnant women (3.5%) received the influenza vaccine. The mean gestational age at the time of influenza vaccination was 26.1 weeks (range, 14-39 weeks). No serious adverse events occurred within 42 days of vaccination, and there was no difference between the groups in the outcomes of pregnancy (including cesarean delivery and premature delivery) and infant medical conditions from birth to 6 months of age.

Conclusion – This study provides good evidence that pregnant women who receive the flu vaccine during the last 2 trimesters of the pregnancy, and their babies at least up to 6 months of age, face no more risks or complications than pregnant women who do not receive the flu shot during the last 2 trimesters of their pregnancy, and their babies up to 6 months of age. It appears the claims of the anti-vaccination crowd are rejected, at least as far as this study is concerned.  The authors concluded as such:

Influenza vaccine that was administered in the second or third trimester of gestation was safe in this study population.

Maternal Flu Vaccination and Effect on Flu Infection in Young Infants

October 6, 2010 2 comments

A new study, published online at the Archives of Pediatrics & Adolescent Medicine, looks at the effects of mom’s flu vaccine on young infants.

Maternal Influenza Vaccination and Effect on Influenza Virus Infection in Young Infants

Angelia A. Eick, PhD; Timothy M. Uyeki, MD, MPH, MPP; Alexander Klimov, PhD; Henrietta Hall, MS; Raymond Reid, MD; Mathuram Santosham, MD; Katherine L. O’Brien, MD, MPH

Arch Pediatr Adolesc Med. Published online October 4, 2010. doi:10.1001/archpediatrics.2010.192

Study Summary – The objective of this study was to assess the effect of seasonal influenza vaccination during pregnancy on laboratory-confirmed flu infections in infants up to 6 months of age. A total of 1160 mother-infant pairs were included in the study. The women gave birth during the regular flu season. Some of them received the flu vaccine, some didn’t. The assignment to either receive the flu vaccine or not was not random. The study authors looked at actual lab-confirmed influenza illnesses (ILI), and ILI hospitalization rates of the infants as the main outcomes. They compared ILI confirmed rates, and ILI hospitalization rates between the infants born to vaccinated mother and infants born to unvaccinated mothers.

Results – Infants born to vaccinated mothers were less likely than infants born to unvaccinated mothers to contract ILI. Specifically:

  • 41% reduction in the risk of laboratory-confirmed influenza virus infection (relative risk, 0.59; 95% confidence interval, 0.37-0.93)
  • 39% reduction in the risk of ILI hospitalization (relative risk, 0.61; 95% confidence interval, 0.45-0.84)
  • Significantly higher hemagglutinin inhibition antibody levels at birth and at 2 to 3 months of age

Conclusion – Methodologically, the main design issue is that test subjects were not assigned randomly to either the vaccine or no-vaccine. Furthermore, it appears from the abstract at least, that the mothers in the no-vaccine group did nor receive a placebo shot. The implication is that they simply did not receive a shot and were aware of it, which would affect the blinding as well.

When taken together these two facts should lower our reliance on the results, although not negate it entirely. The differences of 41% and 39% are too big to be due simply to bias introduced by these design issues. So the conclusion should be that given the large sample size and the large differences between the two groups, this study is highly indicative that babies born to vaccinated mothers do receive a tangible benefit from the vaccine, but the actual reduction in infection and hospitalization rates may be a little less than the numbers reported in this study. These conclusions should be compared to other studies, hopefully studies that had better blinding and randomization.

The author’s own conclusion is as such;

Maternal influenza vaccination was significantly associated with reduced risk of influenza virus infection and hospitalization for an ILI up to 6 months of age and increased influenza antibody titers in infants through 2 to 3 months of age.

3-dose 7-Valent pneumococcal vaccine use associated with increased nasopharyngeal acquisition of pneumococcal Serotype 19A Strain

October 5, 2010 Leave a comment

A recent study published in the Journal of the American Medical Association (JAMA) has found an association between the 7-valent pneumococcal vaccine (PCV-7) and an increase in nasopharyngeal (in the nose and throat) acquisition of pneumococcal serotype 19A strain, which is not one of the 7 strains the PCV-7 protects from. According to the authors of the study, a possible association had been observed between the use of PCV-7 vaccine and a rapid increase in serotype 19A strain acquisition, but studies had never been done to confirm this association, and the current study is the first one to address that concern. Let us look at it:

Pneumococcal Conjugate Vaccination and Nasopharyngeal Acquisition of Pneumococcal Serotype 19A Strains

Elske J. M. van Gils, MD; Reinier H. Veenhoven, MD, PhD; Eelko Hak, PhD; Gerwin D. Rodenburg, MD; Wendy C. M. Keijzers; Debby Bogaert, MD, PhD; Krzysztof Trzcinski, DVM, PhD; Jacob P. Bruin; Loek van Alphen, PhD; Arie van der Ende, PhD; Elisabeth A. M. Sanders, MD, PhD

JAMA. 2010;304(10):1099-1106. doi:10.1001/jama.2010.1290

Study Summary – The study was conducted in the Netherlands. 948  healthy infants, from 6 weeks up to 24 months of age, were enrolled, and followed between July 7, 2005, and February 14, 2008. Infants were randomly assigned to receive 2 doses of PCV-7 at 2 and 4 months; 2 + 1 doses of PCV-7 at 2, 4, and 11 months; or no dosage (unvaccinated control group). Nasopharyngeal swabs were obtained at the age of 6 weeks and at 6, 12, 18, and 24 months to test for the presence of the 19A strain of the pneumococcal bacteria. Rates of bacterial presence were compared between the different groups.

Results – 54 nasopharyngeal serotype 19A carriage isolates from 318 in the 2-dose group, 66 isolates from 327 in the 2 + 1-dose group, and 33 isolates from 303 in the unvaccinated were collected from 6 weeks through 24 months. The cumulative proportion who tested positive for new nasopharyngeal serotype 19A acquisition from 6 through 24 months of age was significantly higher in those having received the 2 + 1-dose PCV-7 schedule (16.2%; 95% confidence interval [CI], 12.6%-20.6%) vs those who were unvaccinated (9.2%; 95% CI, 6.5%-13.0%; relative risk [RR], 1.75; 95% CI, 1.14-2.70) but not after a 2-dose schedule (13.2%; 95% CI, 9.9%-17.4%; RR, 1.43; 95% CI, 0.91-2.25).

Conclusion – This study is methodologically sound. The sample size was fairly large, subjects were randomly assigned, and there was a proper control group. If the results of this study hold, and can be replicated, it would strongly suggest that a 3-dose of the PCV-7 pneumococcal vaccine might lead to higher rates of acquisition of the 19A strain in infants between 6 weeks and 24 months of age. It is very interesting that there were no statistically significant differences between the non-vaccinated children and the ones that had not received the 3rd dose yet. From the information that can be gleamed by the abstract of the study, the authors don’t seem to speculate on why it appears that the 3rd dose makes the difference. They conclude simply as such:

A 2 + 1-dose PCV-7 schedule was associated with an increase in serotype 19A nasopharyngeal acquisition compared with unvaccinated controls.

How should we interpret this study? By the author’s own admission, this is the first study to look at the association between PCV-7 and increased serotype 19A acquisition rates. As such, it is imperative that its results be replicated, to rule out mistakes, or other things that could have affected the results. On the other hand, the study looks to have been conducted well, and appears to have been designed properly. It provides intriguing evidence that 3 doses of the PCV-7 vaccine might be causally related to an increase in nasopharyngeal acquisition of pneumococcal serotype 19A Strain. More studies are needed to verify these results.

Until then, the best course of action is to speak to your pediatrician, and talk to her about using the 13, or the 23, valent version of the pneumococcal vaccine which also covers serotype 19A strains of the pneumococcal bacteria. You should not unilaterally decide to skip the pneumococcal vaccination completely based solely on this one study.

Categories: Pneumococcal, Safety

Vaccines don’t raise arthritis risk in adults

October 4, 2010 1 comment


Common vaccinations don’t raise risk of rheumatoid arthritis, easing fears that they’re linked to the inflammatory disease, according to a new study.

Case reports have suggested vaccines, possibly because of their immune-activating adjuvants, could trigger rheumatoid arthritis, a painful autoimmune disease caused by the body’s natural defenses attacking and inflaming joints.

But a study published online Tuesday in the Annals of the Rheumatic Diseases found no link between common vaccinations for flu, hepatitis, diphtheria and other illnesses and an increased risk for rheumatoid arthritis. The study also found no increased risk for patients getting vaccinations who had a genetic susceptibility to the disease, or who were smokers. Smoking has long been thought to be a major risk factor for the disease.

Receiving multiple vaccines also didn’t up the chances of getting afflicted by the joint disease.

“Our results indicate that immunological provocation of adults with common vaccines in their present form is not a major risk factor for RA,” write the authors, led by Camilla Bengtsson, a researcher at the Karolinska Institute in Stockholm, Sweden. “In addition, our results indicate that active immunization does not increase the risk of RA in individuals with established risk factors.”


Categories: Safety, Safety-General

Reduction in Gastroenteritis With the Use of Pentavalent Rotavirus Vaccine in a Primary Practice

October 2, 2010 1 comment

I have previously looked at studies that looked at acute gastroenteritis (AGE) rates of hospitalizations before and after the introduction of the pentavalent rotavirus vaccine (RV5). Those studies noted a significant reduction in AGE hospitalization rates following the introduction of the RV5 in 2006. In this entry, I will summarize yet another study along the same lines.

AGE, commonly referred to as the “stomach flu“,  is a viral infection, and rotavirus is the leading cause of severe gastroenteritis in children, credited with causing about 50% of acute gastroenteritis hospitalizations during January-June among U.S. children. Logically, if rotavirus causes it, and if an effective vaccine is introduced, we ought to observe statistically significant decreases in gastroenteritis hospitalization rates, and this is what this analysis was set up to do.

The study we will look at today, was published in the journal Pediatrics and the abstract can be accessed by clicking the link below.

Reduction in Gastroenteritis With the Use of Pentavalent Rotavirus Vaccine in a Primary Practice

Rodolfo E. Bégué, MDa, Keith Perrin, MDb

Study SummaryThe authors followed up children under 5 years of age, who presented with AGE in a large pediatrics practice in New Orleans, between 2004 and 2009. Primary care physician office visits, emergency department visits, and hospital admissions were identified by review of records. RV testing was performed only on those who were seen at the hospital. Overall, about 16,000 children were included in this study.

Results – For 2006–2007, 2007–2008, and 2008–2009, 11.1%, 40.3%, and 45.6% of age-eligible children, respectively, received 1 dose of RV5.  As compared with 2004–2005 (before RV5), in 2007–2009, there was a significant decrease in all-cause AGE office visits (23%) and hospitalizations (50%). RV-positive cases (emergency department visits or hospitalizations) decreased by 67%. The decrease in RV-positive cases was more evident among children who were younger than 2 years (81%), with a strong trend among those who were aged 2 to <5 years (41%).

Conclusion – This study adds more evidence that the introduction of the pentavalent rotavirus vaccine led to a significant decrease in all-cause AGE hospitalizations, and especially rotavirus-caused AGE. Taken together with the previous 3 studies we’ve reviewed, the evidence seems very solid and is strongly suggestive of a correlation between the introduction of RV5 in 2006, and significant decreases in AGE hospitalizations. The authors of the above study concluded as such:

Increased use of RV5 in a pediatric practice was associated with fewer AGE office visits and hospitalizations. The reduction was specific for RV-positive AGE and seen among children who were targeted for immunization as well as older groups, suggesting a herd-immunity effect.