Results tagged “vaccination” from Pathophilia

In the original 2009 decision against the petitioner in the Omnibus Autism Proceeding,* Special Master George Hastings found the detection of vaccine-derived measles virus by Unigenetics in an intestinal sample from Cedillo "not reliable." The decision was based partly on expert testimony from Stephen Bustin, PhD, a UK-based molecular biologist who, as part of UK vaccine litigation, had obtained access to the Unigenetics laboratory and some of its relevant data. On the basis of a number of procedural flaws at Unigenetics, Bustin testified both in the UK and US courts that the company's work was plagued with potentially contaminating errors. Bustin also suggested that results from Unigenetics might even be fraudulent, after reviewing some of the laboratory's altered notebooks.

Access to documents from Unigenetics, on which Bustin based his expert opinion, was the crux of a recent appeal by Cedillo's parents to the US Court of Appeals for the Federal Circuit. This appeal was denied Friday, August 27th. And while the appeal court ruled that Special Master Hastings "erred in permitting the government to introduce the expert reports and testimony of Dr. Bustin because the government did not make available the underlying Unigenetics documents upon which Dr. Bustin relied," the court also noted that Hastings had given the petitioners virtually every opportunity to obtain this information from the UK court themselves, which they apparently did not try to do. (It should be noted that the government argued against the reliability of Unigenetics with other expert testimony. It is presumed on this basis that the Special Master's error was not a reversible one.)

In 2007, the government, in its case preparation, successfully petitioned the UK court to release the Bustin reports, but it did not request the laboratory notebooks or other data on which Bustin relied. The appellate decision further describes the background facts, 

The government explained at oral argument that UK counsel informed them that an application to the UK court requesting "everything" from the UK litigation would be denied as overbroad, and as a result, they needed to narrow their request to the most essential items. The government therefore subsequently "honed down" their request to cover solely the three reports, two of which were filed by Dr. Bustin, that they eventually obtained.

The upshot: Cedillo v. US DHHS has been put to bed.

In a coda to this case, it can be said that life, outside the courtroom, moves relatively quickly and in curious directions. Unigenetics dissolved as a company 5 years ago, although its former director, pathologist John O'Leary, is evidently still working in Dublin at Trinity College. In 2008, O'Leary, in an apparent effort to regain academic credibility, was coauthor of a multi-institutional study ("Lack of association between measles virus vaccine and autism with enteropathy: a case-control study" in PLoS One) that essentially negated the results produced by his own company for Cedillo.

DHHS = Department of Health and Human Services; MMR = measles-mumps-rubella.

* Which was affirmed by Judge Thomas Wheeler in the US Court of Federal Claims.

The "too many, too soon" rant, which is predicated on the convoluted idea that multiple vaccinations overwhelm the immune system and thereby cause autism, has been thoroughly shot down by logical argument and now by a recent study in the journal Pediatrics.

Mining the Vaccine Safety Datalink, physicians at the University of Louisville in Kentucky compared the long-term neuropsychological outcomes of children who received on-time vaccinations during their first year with those who didn't. The cut-to-the-chase result: children who received timely vaccinations generally performed better and certainly no worse than less vaccinated kids. The study was based on a previous CDC study, which showed no association between exposure to thimerosal, a long-time vaccine preservative containing microgram amounts of ethylmercury, and autism.

At Medscape, CHOP pediatrician Paul Offit (Satan incarnate to antivaccinationists) offers his predictable and correct perspective on the study, saying,

I think parents can be reassured here that a choice to delay vaccines or to not give vaccines does not in any sense decrease the risk of a neurological outcome or autism. All it does is increase the period of time during which children are susceptible to vaccine-preventable diseases.

CDC = Centers for Disease Control and Prevention; CHOP = Children's Hospital of Philadelphia.

The reasons for their enthusiasm:

• Encouraging results from the large vaccine trial (RV144) in Thailand, which was reported last year.
• The prevention or control of infection with simian immunodefiency virus (a monkey correlate of HIV) in preclinical studies by using "new vaccine approaches."
• The identification of "vulnerable" HIV targets by using broadly neutralizing mAbs.

Data from these investigations can and/or will be used to tweak (for lack of a better word) candidate vaccine regimens against HIV. Specifically in the short term, investigators will attempt to define the immune mechanisms that conferred protection in the Thai trial and then create a vaccine regimen (eg, multiple prime and boost shots) to maximize those responses. Koff and Berkley predict follow-up clinical trials to be under way by 2013. (That's sooner that the legislated kick-off of ObamaCare.)

Successful vaccine development will necessitate the cooperation of government, academia, and industry and will demand, of course, lots of money. Koff and Berkley advise that the global financial crisis should not thwart the forward movement of vaccine development at this promising stage. One visible backer is Bill Gates, who recognizes the big hurdles to a successful HIV vaccine and is scheduled to speak at the Conference, says the WSJ Health Blog.

Preliminary data

Within EIP's surveillance area, there were 326 cases of GBS (meeting case criteria) between October 1, 2009, and May 10, 2010. Among these patients, 27 received documented vaccination against the 2009 pandemic H1N1 virus during the 42 days preceding their illness, and 274 did not (the vaccine status of 25 was unknown or "pending ascertainment"). Consequently the estimated age-adjusted rates of GBS were 1.92 and 1.21 per 100,000 person-years among vaccinated and unvaccinated persons, respectively. These data led to an attributable excess risk of GBS with vaccination of 0.8 per 1 million vaccinations.

Once again, it's important to remember that association does not mean causation. For instance, many of the vaccinated persons (59%) also reported illness symptoms during the 42 days before GBS onset, which is consistent with many cases of non-vaccine-related cases of GBS. Vaccination, in these cases, could have been completely incidental to the development of neuropathy. Moreover, there was no temporal clustering of GBS onset after vaccination (eg, at 2 weeks), suggesting that vaccine was not causally related to illness. Vaccinated persons with GBS were not sicker, nor did they suffer worse outcomes, than unvaccinated individuals with GBS.

The CDC advises that the final assessment of the EIP data will be available in the fall of this year. Other safety databases, like the Vaccine Safety Datalink, have not shown an association between GBS and receipt of the 2009 pandemic H1N1 vaccine.

* A collaboration among the CDC, state health departments, and academic centers in 10 states. Surveillance covers about 45 million individuals.

The new vaccine differs from the most notable cancer-preventing vaccine, Merck's Gardasil, in that it targets an autoantigen, alpha-lactalbumin, not a cancer-associated virus, like HPV. Alpha-lactalbumin is a breast-specific protein that is overexpressed in most breast cancers and during lactation, but not in normal breast tissue of nonlactating women. In transgenic mouse models of breast cancer, disease was prevented in all inoculated animals, while unvaccinated mice developed cancer. The vaccine also stymied the growth of existing tumors.

The excitement of the study's lead investigator, Vincent Tuohy, PhD, is palpable: "If it works in humans the way it works in mice, this will be monumental. We could eliminate breast cancer," he says in the press release. Tuohy proposes that the vaccine would be appropriate for women older than 40, when pregnancy (and lactation) is less likely and the risk of breast cancer rises.

Human trials of the vaccine may begin within the year, reports the Clinic.

HPV = human papillomavirus.

Now the FDA is reporting that Merck's vaccine contains DNA fragments of PCV1 and PCV2. Merck evidently detected the nucleic acids in its product with a more sensitive assay, reports the WSJ. PCV2, like PCV1, does not cause human disease; however, it may sicken pigs. Merck and the FDA speculate that the source of the DNA fragments may be trypsin, a protease which is used in the cell-culture growth of the attenuated vaccine virus.

Commercial trypsin may be obtained from bovine or porcine pancreas. According to one commercial pamphlet, the enzyme can be contaminated with porcine viruses, especially porcine parvovirus (which is not known to cause human disease). There is evidently some give and take when using methods (eg, chemical or filtering) to inactivate or remove contaminating viruses during trypsin manufacture. Gamma irradiation and heat inactivation, while "officially recognized," are "aggressive" and affect trypsin yield, says PAA. Short wave-length UV light is advocated by the company to destroy viral nucleic acids, without compromising the biologic activity of trypsin.

According to the FDA by way of the WSJ, both Rotarix and Rotateq have been given to millions of babies to reduce the risk of gastrointestinal disease due to rotavirus. However, given that trypsin may be the source of the PCV DNA fragments and is used widely in the biotech industry, contamination may extend well beyond mere vaccine production.

My speculation: Vast potential for the contamination of products with viral nucleic acids with negligible or no risk of illness.

Today's FDA meeting, which was already scheduled to discuss the potential safety issues of PCV1 DNA in Rotarix, will also address the newly found DNA fragments in Rotateq.

* Live, attenuated.

** Meaning that the safety of the contaminated Rotarix vaccine was assessed in approval-required clinical studies.

Image of commercial trypsin from PAA.

05/08/10 update: Yesterday an FDA advisory panel recommended the continued use of Rotarix and Rotateq, according to the WSJ and other news sources. It should be stressed that, while some coverage (I'm talking about you, MedPage Today) indicates that the actual viruses PCV1 or PCV2 are present in the vaccines, only DNA fragments of the viruses have been detected. This fact substantially reduces, if not eliminates, any infectious possibility. Moreover, neither virus is known to cause human disease.

05/15/10 update: Yesterday the FDA sanctioned the continued use of both the Rotarix and Rotateq vaccines. The decision was "[b]ased on a careful review of a variety of scientific information." In hindsight, FDA officials—in a pervasive, overly cautious frame of mind—jumped the gun when it first suspended the use of Rotarix in March.

The 2009 H1N1 (or swine flu) vaccination campaign began in earnest in mid-October of last year, and approximately 100 million vaccinations were administered in the United States. Consequently the rate of GBS associated with vaccination was 3.5 per 10 million. All but 1 case occurred within 6 months of vaccination; 23 cases occurred within 2 weeks of inoculation. The annual background rate of GBS is about 1-4 cases per 100,000. (The 2009 H1N1 vaccine protects against GBS, anyone?)

Original worries about a vaccine-associated increase in GBS stemmed from the observed rise in the condition during the 1976 swine-flu vaccination program.

VAERS = Vaccine Adverse Event Reporting System.

How GSK learned of the presence of PCV1 DNA fragments in Rotarix is somewhat sketchy in detail. According to the FDA, an "independent US academic research team," while assessing a number of vaccines with a "new technology," detected the PCV1 DNA fragments. After finding the DNA fragments in 2 lots of Rotarix vaccine, the researchers alerted GSK on February 9th. Follow-up tests by the company confirmed the presence of the DNA fragments in the 2 tested lots, as well as samples leading back to the seed virus. GSK notified the FDA on March 10th, and the agency, as a precautionary measure, suspended the use of Rotarix yesterday.

The GSK press release provides 2 references on PCV1:

Li L, Kapoor A, Slikas B, et al. Multiple diverse circoviruses infect farm animals and are commonly found in human and chimpanzee feces. J Virol. 2010;84:1674-1682. (From the Blood Systems Research Institute in San Francisco.)

Hatterman K, Roedner C, Schmitt C, Finsterbusch T, Steinfeldt T, Mankertz A. Infection studies on human cell lines with porcine circovirus type 1 and porcine circovirus type 2. Xenotransplantation. 2004;11:284;294. (From the Robert Koch Institut in Berlin.)

Li et al used something called viral metagenomics to identify "circovirus-like" DNA sequences in stool samples of humans and wild chimpanzees. Viral metagenomics is apparently a relative new field, in which researchers attempt to recover viral DNA from environmental samples (as opposed to laboratory cell lines).* In US adults, the detection of circovirus was limited to the discovery of porcine circovirus (which is also found in most US pork products, according to the authors).

Hatterman et al reported on their infection of human cell lines with PCV1, which did not cause "any visible changes," unlike the type 2 PCV strain.

For children who require rotavirus vaccination, the FDA recommends the use of Merck's Rotateq vaccine—which is evidently not contaminated with PCV1 DNA.

* The technique may (may) be the method by which PCV1 DNA fragments were detected in GSK's Rotarix vaccine.

Image of Rotarix administration from Rotarix Prescribing Information.

03/26/10 addendum: Relying on reason and common sense, the European Medicines Agency reported today that it "sees no safety concerns with the Rotarix oral vaccine" and that the DNA of a virus that does not cause human disease "does not present a risk to public health." The EMA stressed that PCV1 is commonly found in meat and other food products.

The agency, however, requested that 1) GSK identify how the DNA fragments got into Rotarix and 2) produce a vaccine that is free of PCV1 DNA. The agency also reported that other GSK vaccines do not contain PCV1 DNA. 

Among the many opinions rendered in the decisions from the Special Masters (see here, here, and here) are discussions of the autism studies published by Mark and David Geier—whose work has been criticized sharply and at length at this blog and in my 2009 letter to the Journal of the Neurological Sciences.

The court's Special Master George Hastings, for instance, writes in his decision re King v Secretary of Health and Human Services: 

[M]ost of the epidemiologic studies that have addressed the thimerosal/autism causation issue have failed to find any association between thimerosal-containing vaccines and autism, but there have been certain exceptions. Those exceptions were studies published by the research team of Dr. Mark Geier and his son David Geier[*]...To be sure, the petitioners in this case have not cited or relied upon those Geier studies in their post-hearing briefs, because, as I will discuss below...the petitioners argue that all of the epidemiologic studies done to date are irrelevant to the petitioners' causation theory in this case. However, since I find that the epidemiologic studies are of relevance, I have found it reasonable to examine those Geier studies, to see if they afford any significant counterweight to the many contrary studies...

After careful consideration, I conclude that the Geiers' studies cannot be given any weight. A number of those studies were considered by the Institute of Medicine (IOM) committee that fully studied the entire thimerosal/autism causation issue in 2004. That committee concluded that the studies were so flawed as to be "uninterpretable," and that the studies contributed nothing meaningful ("noncontributory") concerning the causation issue...The committee noted that the studies were based on databases that themselves had "significant limitations"...and that the studies had "serious methodological problems"...or "serious methodological limitations"...The committee added that the Geiers' articles describing their analytical methods were "not transparent" and omitted "important details," so that it was impossible to evaluate the studies...Other specific deficiencies in the studies were also discussed, including the fact that the Geiers incorrectly used several epidemiologic terms and measures. 

In addition, Dr. Fombonne [respondent's expert] agreed with the IOM's criticisms of the Geier studies, and testified that the Geier studies in general failed to use accepted epidemiologic methods...Dr. Rutter [respondent's expert] was critical of the Geier studies as well...Further, petitioners' own expert witness concerning epidemiology, Dr. Greenland, agreed with the criticisms of the Geier articles, acknowledging that those studies are "deficient in methodology"...And none of the expert witnesses for the petitioners vouched for the reliability of the Geier studies.

I have reviewed the published Geier studies discussed in the 2004 IOM report, and I agree with the analysis of those studies set forth in that IOM report. Further, I have reviewed the additional studies published by the Geiers since the 2004 IOM report, and find that those studies suffer from the same type of flaws as the earlier Geier studies. That view includes a study published in 2008 by the Geiers, along with Young as the third author. Two of  respondent's experts, Drs. Fombonne and Rutter, testified that that 2008 study was again deeply flawed, and those experts provided a number of specific examples of deficiencies in the study...And, again, none of the petitioners' experts testified in support of that 2008 Young, Geier, and Geier study.

In summary, I conclude that all of the Geier epidemiologic studies are not reliable, and cannot be accorded any weight.

In a lengthy footnote from the decision handed down in the case of Mead v Secretary of HHS, Special Master Patricia Campbell-Smith writes,

Although the studies conducted by Dr. Mark Geier and his son purport to find an association between thimerosal-containing vaccines and autism, their studies have been criticized consistently by various reviewers, including petitioners' own expert epidemiologist, as methodologically deficient...(Dr. Rutter [characterized] the 2008 Young study—that was conducted in part by Dr. Geier and his son...as a poorly designed study for the following reasons: (1) the researchers used a "strange" study design that is both a cohort study [a controlled study] and a time-trend analysis of the available database information [an ecological study] and (2) the researchers included emotional disturbance as one of the neurodevelopmental disorders observed following exposure to thimerosal-containing vaccines even though emotional disorders are not included in any of the official psychiatric classifications systems for neurodevelopmental disorders). The undersigned has reviewed carefully the presented studies conducted by the Geiers and has considered the criticisms leveled against the Geiers' studies. Persuaded that the studies are flawed methodologically in critical respects, the undersigned, without addressing the studies in extensive detail here, declines to accord any evidentiary weight to the studies. The undersigned notes that other researchers have been unable to verify the validity of the Geiers' statistical analysis on a number of occasions and a number of courts have expressed concerns about the reliability of their work.

Campbell-Smith goes on to cite 8 court cases in which the Geiers' work was called, among other things, "unintelligible," or in which Dr. Geier's testimony was described as "not reliable."

In her decision for the third test case, Special Master Denise Vowell affords special attention to the Young, Geier, and Geier study of 2008—which was specifically pulled apart at this blog and by Epi Wonk.

The only studies demonstrating a relationship between TCVs [thimerosal-containing vaccines] and ASD [autism spectrum disorder] are those in which Dr. and Mr. Geier appear as co-authors, including the Young study published in May, 2008, and funded by the OAP PSC [Omnibus Autism Proceeding Petitioners' Steering Committee]...Because petitioners’ own expert commented that the Geier studies were not reliable as evidence... and they were thus not addressed by respondent’s experts, I do not discuss the earlier Geier studies any further. In view of the numerous criticisms of the earlier Geier studies and petitioners' own expert’s dismissal of them, I have placed no reliance on them.

The Young study was an ecological analysis using the VSD database...Doctor Greenland [petitioners' expert] did not comment on this study during his testimony, as the article was introduced after his appearance and excusal. The study found an increased risk of ASD, based on increasing exposure to TCVs. Doctor Fombonne offered several criticisms of this study. In a critique common to many of the studies performed by Dr. and Mr. Geier, Dr. Fombonne commented that the Young article did not provide the data that would allow others to verify the calculations performed.

Doctor Fombonne reproduced one chart from the article...Using the chart, he explained that the birth cohorts used in the study did not all contain the same number of individuals, with most representing 40,000 children...One birth cohort, that of children born in 1990, contains only 2,000 children...When this "outlier" is removed, the purported statistical relationship between ASD and TCVs during the first four years of the sample disappears.

Doctor Fombonne was also highly critical of the authors' addition of invented numbers to the 1995 and 1996 data from the VSD...If the adjustments are removed, there is no correlation at all between the increase in thimerosal exposure and increase in autism cases per 10,000...Doctor Fombonne commented: "It’s dishonest to impute like 45 new cases which are just invented to top up the prevalence in a way which is supportive of their hypothesis. It’s clear that these investigators have a clear track record to do with the data that supports their hypothesis. And I’ve seen that in their previous papers."

Doctor Rutter offered similar criticisms of the Young study...calling it "a poor study for several different reasons"...It began with a cohort design, but ended up being analyzed as a time trend study. That required the authors to make adjustments to the first and last cohorts. Doctor Rutter described this as "putting together chalk and cheese in the hope of gazpacho soup coming out"...The "analytic design and strategy was not a satisfactory one."

He pointed to Table 3 as a striking example of the poor design...Table 3 compares "neurodevelopmental disorders" to several control disorders, measuring the difference in rates of the disorder developing in the cohorts that received 100 micrograms more mercury. The table shows higher rate ratios for autism, ASD, ADD/ADHD, developmental or learning disorders, disturbance of emotions, and tics...Doctor Rutter called this table an example of demonstrating a statistical effect without showing a causal effect...If the neuroinflammation hypothesis is correct, it is difficult to explain how neuroinflammation causes tics or disturbance of emotions. The study reported TCV effects across a very broad range of unconnected disorders having different ages of onset, different genetic factors, and different disease courses...The broad range of effects in these diverse disorders caused Dr. Rutter to be "immediately skeptical as to what [the study] shows."

He also questioned why "disturbance of emotions" was listed in the category of neurodevelopmental disorders, noting that anyone knowledgeable about the field of neurodevelopmental disorders would not have categorized it as one, and would have placed it with the control disorders...To prove their hypothesis that increased mercury exposure causes increases in neurodevelopmental disorders but not control disorders, the authors have to demonstrate that mercury is associated with increased rates of one but not the other. If "disturbance of emotions" was properly placed with the list of control disorders, it would undercut the authors' hypothesis. Their comparison between the two groups is therefore invalid.

N.B.--The Geier studies reviewed by Special Master Hastings included the following:

Geier DA, Geier MR. An assessment of the impact of thimerosal on childhood neurodevelopmental disorders. Pediatr Rehabil. 2003;6:97-102.

Geier DA, Geier MR. A comparative evaluation of the effects of MMR immunization and mercury doses from thimerosal-containing childhood vaccines on the population prevalence of autism. Med Sci Monit. 2004;10:P133-P139.

Geier DA, Geier MR. A two-phased population epidemiological study of the safety of thimerosal-containing vaccines: a follow-up analysis. Med Sci Monit. 2005;11:CR160-CR170.

Geier DA, Geier MR. An evaluation of the effects of thimerosal on neurodevelopmental disorder reported following DTP and Hib vaccines in comparison to DTPH vaccine in the United States. J Toxicol Environ Health A. 2006;69:1481-1495.

Geier DA, Geier MR. An Assessment of downward trends in neurodevelopmental disorders in the United States following removal of thimerosal from childhood vaccines. Med Sci Monit. 2006;12:CR231-CR239.

Geier DA, Geier MR. A meta-anlysis epidemiological assessment of neurodevelopmental disorders following vaccines administered from 1994 through 2000 inthe United States. Neuro Endocrinol Lett. 2006;27:401-413.

Geier DA, Geier MR. A case series of children with apparent mercury toxic encephalopathies manifesting with clinical symptoms of regressive autistic disorders. J Toxicol Environ Health A. 2007;70:837-851.

Geier DA, Geier MR. A prospective assessment of porphyrins in autistic disorders: a potential marker for heavy metal exposure. Neurotox Res. 2006;10:57-64.

Geier MR, Geier DA. Thimerosal in childhood vaccines, neurodevelopment disorders, and heart disease in the United States. J Am Phys Surg. 2003;8:6-11.

Geier MR, Geier DA. Neurodevelopmental disorders after thimerosal-containing vaccines: a brief communication. Exp Biol Med (Maywood). 2003;228:660-664.

Cases: 57 million; range, 41-84 million. Most cases were among 18-64-year-olds (58%) and children (33%).

Hospitalizations: 257,000; range, 183,000-378,000 (calculated mid-level hospitalization rate, 0.45%). Most hospitalizations were for 18-64-year-olds (58%) and children (32%).

Deaths: 11,690; range, 8330-17,160 (calculated mid-level death rate, 0.02%). Most deaths affected 18-64-year-olds (77%).

Although H1N1 activity has been relatively low during the last 5 weeks of assessment (from mid-December to mid-January), the CDC isn't ready to call the pandemic over.

[T]here are still uncertainties surrounding the rest of this flu season, including the possibility of increases in circulation of seasonal influenza viruses and increases in circulation of 2009 H1N1 viruses. In past pandemics, flu activity has occurred in waves and it’s possible that the United States could experience another wave of flu activity.

The CDC continues to urge vaccination against pandemic influenza and reports that supplies are abundant for all eligible comers—including the elderly. A recent interim report of vaccination coverage indicates that nearly 90% of nonelderly adults with medical conditions (an original at-risk target group) remain unvaccinated.

Depiction of H1N1 virus from Wikipedia.

The continuing mumps outbreak in New York and New Jersey—which has affected more than 1500 individuals, most of them Orthodox Jewish boys—is traced to an 11-year-old who visited Britain in June of last year, reports the CDC.

More than 7400 laboratory-confirmed cases of mumps were recorded in the United Kingdom in 2009. The case number is lower than those seen during the epidemic of 2004 and 2005, the UK Health Protection Agency reports, but greater than cases reported during 2007 and 2008.*

The US mumps outbreak continues despite the relatively high rate of vaccination among the infected—88% had received at least 1 vaccine dose; 75%, 2 doses. However, the mumps component of the MMR vaccine provides less protection than the measles or rubella components. The CDC provides an estimated mumps-vaccine efficacy of 73%-91% after 1 dose and 79%-95% after 2 doses.

Among the most common symptoms of mumps among boys is orchitis, or testicular inflammation. According to one source, about 20% of prepubertal boys will develop this painful condition. Consequent risks include testicular atrophy and sterility.

* A resurgence of mumps and measles cases in the United Kingdom is blamed on reduced vaccination rates--which are believed to be (at least partly) the result of the 1998 study of Andrew Wakefield et al linking the MMR vaccine with autism. The discredited study was recently retracted by The Lancet.

Photo of child with parotid gland swelling due to mumps from the CDC/NIP/Barbara Rice.

That rang 12 years ago.

Yesterday, editors of The Lancet officially retracted publication of a 12-year-old debunked study that linked the MMR vaccine to autism, according to the journal's web site, numerous news sources, and countless blogs. The study is believed to be responsible for declining vaccination rates among children in the United Kingdom and the resurgence of measles.

The journal's decision comes on the heels of an announcement last week from the UK's General Medical Council, which found that 3 of the article's authors—Andrew Wakefield, John Walker-Smith, and Simon Murch—did not act in the best interests of the study's 12 pediatric enrollees. Wakefield, in particular, was cited for "callous disregard" toward his subjects, by plying them with a few pounds in exchange for blood samples at a birthday party. The GMC's report is provided courtesy of Kathleen Siedel at her neurodiversity blog.

The Council's investigation of Wakefield and others was prompted by the investigative reporting of Brian Deer from The Sunday Times. Beginning in 2004, Deer alleged that Wakefield not only held significant financial conflicts of interest, but that he actually manufactured data. Responding to Deer's initial investigation, 10 of the study's 13 authors (including Walker-Smith and Murch) retracted their "interpretation" in a letter to The Lancet.

So where does a discredited UK doctor go? Austin, Texas, evidently. Wakefield is Executive Director of The Thoughtful House Center for Children, a questionable research and treatment center for children with autism. However, Wakefield does not have a license to practice medicine in the state, according to the online database of the Texas Medical Board.

The foundation's new support is motivated by recent data from the Johns Hopkins Bloomberg School of Public Health, which showed that a 90% vaccination-coverage level* in developing countries would prevent the deaths of about 7.6 million young children during the next decade. The number of lives saved could be ramped up to 8.7 million, if a malaria vaccine is introduced in the year 2014.

Another inspiration for the Gateses' pledge is the success of the rotavirus vaccine. In this week's NEJM, pooled results of a randomized, multicenter trial in South Africa (n = 3166 infants) and Malawi (n = 1733 infants) showed that a live, oral rotavirus vaccine (Rotarix; GSK) reduced cases of severe gastroenteritis due to the organism by 61% (4.9% vs 1.9%).** 

Also reported in this week's issue, the recent introduction of rotavirus vaccines in Mexico reduced diarrhea-related deaths by 35% among children younger than 5 years of age (18.1 vs 11.8 deaths per 100,000 children). The life-saving benefit of vaccination was even more apparent among infants younger than 11 months (41% mortality reduction).

Vaccine researchers looking for a chunk of the Gateses' big money can start here. But the foundation only accepts letters of inquiry (LOIs) from 501(c)(3) organizations and other nonprofits. Individuals need not apply.

* Which would include new vaccines for diarrheal illnesses and pneumonia.

** Although there was no significant difference in mortality, 2.5% vs 2.6%.

No. 1: Pandemic H1N1

You were expecting something else?

Coming out of left field (ie, Mexico)* in April, the novel 2009 H1N1 ("swine flu") virus caused an official global pandemic in June, according to the World Health Organization. Cases mounted rapidly, but fear of disease was mitigated by its relatively low mortality rate.** Drawing on their experience from the swine-flu epidemic of 1976, leading US neurologists first believed that a government-led vaccination campaign would be unlikely because of 1) low mortality and 2) the possibility of vaccine-associated Guillain-Barre syndrome (GBS). Boy, were they wrong.

In August, the CDC released its recommendations for the administration of developing H1N1 vaccines to 5 groups. The surprise: Instead of the historically targeted elderly, the CDC prioritized vaccination for children, young adults, and pregnant women because of their emerging risks of disease-related complications and death. Consequently vaccination was recommended for an estimated 159 million Americans as soon as vaccines became available, sometime in mid-October.

In May, the DHHS had contracted with 5 companies—CSL Biotherapies, GSK, MedImmune, Novartis, and sanofi-pasteur—to produce either injectable or nasally administered vaccines for pandemic H1N1 to the tune of $932 million. Government orders for another $883,977,920 and $438,143,025 were placed in July and September, respectively. The total amounted to about 9 bucks per vaccine, which was being produced by the traditional method of viral incubation in fertilized chicken eggs.

This tried-and-true method ultimately led to a delay in vaccine production for 2 primary reasons: the fastidious nature of the 2009 H1N1 virus (when compared with seasonal influenza viruses) and limited chicken eggs. Turns out the pandemic virus required 2 eggs to create a single vaccine dose, instead of the usual one. By October, the federally contracted companies had only cranked out about 10% of the promised 120 million vaccine doses for US residents. Time was a-wastin'.

In October, the CDC investigators estimated that about 3 million citizens had already experienced symptomatic pandemic flu between April and July, on the basis of a probabilistic model. Confirming previous assessments, the incidence of disease and disease-related hospitalizations were considerably higher in children and young adults. Pandemic flu, overall, had necessitated about 14,000 hospitalizations and had caused about 800 deaths in the United States.

The following month, the CDC estimated that up to 34 million Americans had been infected between April and mid-October. Respective hospitalizations and deaths now ranged from 63,000 to 153,000 and from 2500 to 6000. Another age breakdown revealed that disproportionate numbers of younger adults (and to a lesser extent, children) remained susceptible to pandemic flu generally and severe disease specifically. About 45% of Americans who had died from pandemic flu had been healthy.

And then disease began to wane. Earlier this month, only 25 states reported widespread activity. At the same time, data showed that the pandemic flu vaccines (the supplies of which were up) remained effective and were comparably safe. Specifically the risk of GBS appeared no higher than the typical background rate.

The latest recommendations: More than 30 "major health care provider organizations," including the American Medical Association, the American Academy of Pediatrics, and the American Red Cross, are encouraging all US residents to receive a pandemic flu vaccine in anticipation of another wave of infection. An "open letter" to the American people states,

The H1N1 flu vaccine is safe, effective, and the best way to protect yourself and your family from the H1N1 flu. Over 110 million doses...are now available, with more coming every day. Now is the time to protect yourself and those around you by getting vaccinated against the H1N1 flu.

Links to selected Pathophilia posts on pandemic flu (and a few on seasonal flu) are provided here in chronological order.

• WHO: Not-So-Deadly Swine Flu Now Pandemic
• Caution for Today: GBS Risk With Old Swine-Flu Vaccine
• Rapid H1N1 Test Relatively Insensitive
• CDC Recommends Novel H1N1 Vaccine for Certain Groups
• Novel H1N1 Mortality Rate: Pitfalls in Calculation
• Novel H1N1 Infection in Chicago: Children Preferentially Vulnerable
• Novel H1N1 Vaccine Approval for 4 of 5 Companies
• Harvard Expert Estimates Very Low Mortality Rate for 2009 H1N1 Pandemic
• Vaccinations for Seasonal and Pandemic Flu
• Strep Pneumoniae Most Likely Bacterial Pathogen in Fatal H1N1
• H1N1 Vaccine Table
• ...And Furthermore, Bill Maher Needs a Haircut
• H1N1 Vaccine Shortage: Blame Chickens
• The Solace of Illusion
• Influenza: Moms' Reasons for Not Vaccinating
• Millions of Americans Infected With Pandemic Flu
• Reanalysis Negates Recommendation for N95 Respirators
• Seasonal Flu Vaccine: High Demand Leads to Short Supply
• After Delay, FDA Approves GSK's Pandemic Flu Vaccine
• Seasonal Flu Vaccine and Protection Against Pandemic Flu
• CDC: Up to 34 Million Americans With Pandemic Flu
• CDC: Modest Decline in H1N1 Activity
• Norwegian H1N1 Mutation Not New
• Pandemic H1N1: Activity Down; Vaccine Supplies Up
• Pandemic Flu Vaccines Comparably Safe
• Overall H1N1 Mortality in England Comparable to US Estimates

* Instead of the historically expected East Asia.

** Estimated in the United States at 0.007%-0.032%.

Depiction of H1N1 virus from Wikipedia.

No. 4: Medical Science Crawls Toward an HIV Vaccine

In October, peer-reviewed results of a mammoth Thai trial (>16,000) showed modest (and possibly statistically significant) protection against HIV infection after a series of shots in moderate-risk adults. The trial results, although only marginally positive, are generating optimism after 2 decades of failure and, specifically, 3 negative trials (published in 2005, 2006, and 2008) of assorted vaccine regimens in high-risk adults.

In the latest placebo-controlled Thai study, vaccine efficacy—defined as the percentage reduction of HIV infection—climbed to a significant 31.2% in the modified intent-to-treat analysis.* Compare this value with the highest estimated vaccine efficacy in the previous large-scale studies, only 6%, and you get an idea of why some investigators believe that we're actually getting somewhere.

The trial's vaccine regimen consisted of 4 "priming" injections of a recombinant canarypox-vector vaccine (Alvac-HIV; sanofi-pasteur) and 2 booster shots of a recombinant glycoprotein-120 subunit vaccine (AIDSVAX B/E; VaxGen). The prime-boost vaccination series was chosen on the basis of previous trials (Belshe et al, 1994; Russell et al, 2007; and AIDS Vaccine Evaluation Group 022 Protocol Team, 2001), wrote the study investigators. Previously unsuccessful vaccine regimens in high-risk adults consisted of 7 injections of VaxGen's AIDSVAX B/B vaccine; 7 injections of VaxGen's AIDSVAX B/E vaccine; and 3 injections of Merck's trivalent adenovirus-vector vaccine.

The next steps are to determine the immune mechanisms that conferred protection in the Thai trial and to create a vaccine that will maximize those responses.

HIV = human immunodeficiency virus.

* Which excluded 7 individuals who were discovered to have HIV infection at baseline.

Lack of funds may stall the Measles Initiative, a multi-organization program designed to reduce the worldwide mortality of measles. Despite the fact that all regions, except for Southeast Asia, have achieved the United Nations goal of reducing measles mortality by 90% from 2000 to 2010 (and have, thereby, prevented 12.7 million measles deaths), the reduction in measles mortality has leveled off since 2007, and the Initiative is facing a funding gap of $59 million, reports the World Health Organization. (WHO's complementary report on the progress toward reducing measles-related deaths can be found in the latest issue of the MMWR.)

Lack of financial resources could suspend the Initiative's pivotal vaccination efforts next year in densely populated regions like China, Indonesia, Pakistan, Bangladesh, Vietnam, Nigeria, and Ethiopia. And because measles is highly contagious, the disease can flourish rapidly if immunity is lacking, report WHO officials.

Although measles-related deaths fell 78% globally, from 733,000 in 2000 to 164,000 in 2008, 77% of last year's deaths (126,000) occurred in Southeast Asia. Experts fear that there could be a significant uptick in measles-related deaths, to an estimated 1.7 million between 2010 and 2013, if vaccination efforts do not continue.

Estimated No. Measles Deaths, 2000-2008, and Projected Deaths, 2009-2013

^§ 95% uncertainty intervals.

Data from VAERS*—which includes publicly volunteered information—reveal overall adverse-event (AE) rates of 82 per 1 million doses of pandemic flu vaccine (0.0082%) and 47 per 1 million doses of seasonal flu vaccine (0.0047%). Respective rates of serious AEs (eg, death, life-threatening illness, hospitalization, prolonged hospitalization, persistent or significant disability, congenital anomaly) are 4.4 and 2.9 per 1 million vaccine doses each. However, the percentage of serious AEs among all reports is slightly higher with seasonal flu vaccines (6.1% vs 5.4%). No substantial differences are noted between pandemic and seasonal flu vaccines in the types of serious AEs reported, and no AE differences between injectable and intranasal vaccines are apparent.

Among the 13 reported deaths of those who received the pandemic flu vaccine, 9 were associated with a "significant" underlying illness; 1 was the result of a motor vehicle accident; and 3 cases are under review by the CDC. There are 12 reports of Guillain-Barre syndrome (GBS), 4 of which currently meet diagnostic criteria, and 19 reports of possible anaphylaxis. (The background incidence of GBS is 1-2 per 100,000.)

In the VSD**—which includes data from more than 400,000 vaccinated individuals among 8 managed-care organizations—there are no reports of GBS and only 1 case of anaphylaxis. Increased rates of other neurologic or allergic conditions have not been detected.

Historically higher rates of GBS associated with the swine-flu vaccination in the mid-1970s may be related to contemporary methods of vaccine production, the CDC speculates. The Center reports that it continues to monitor vaccine-associated AE data and advises that the number of vaccines administered in the VSD population, in particular, may be too small as yet to detect an increased risk of vaccine-associated GBS.

As of December 3rd, more than 72 million doses of pandemic flu vaccine have been allocated in the United States.

N.B. The CDC states that it used a number of methods (eg, advertising in medical journals) to enhance the reporting of vaccine-associated AEs to VAERS this season.

* As of November 24, 2009.

** From October 1 to November 21, 2009.

Only 25 US states are reporting widespread activity of pandemic influenza, according to the latest update from the CDC. During the previous 3 consecutive weeks, widespread activity was reported in 46, 43, and 32 states. The CDC advises, nevertheless, that most indicators for flu activity remain higher than normal for this time of year.

As of December 3rd, more than 72 million doses of pandemic flu vaccine have been allocated (ie, ready for distribution) in the United States; more than 63 million have been shipped to ordering states or US territories. Approximately one half of the supplies have been allocated for 10 states.

* Including New York City.

It's not an original thought, but Hassan (like the rest of us) recognizes that we're probably on the cusp of finally realizing tailored or boutique-style medicine. One case in point is the apparent, relative benefit and safety of the anti-amyloid bapineuzumab (JNJ; Wyeth) in individuals with Alzheimer disease who don't carry the ApoE4 allele.

In a more tangible way, genomics is informing the development of vaccines and the control of infectious diseases. In a recent PLoS review article ("The Key Role of Genomics in Modern Vaccine and Drug Design for Emerging Infectious Diseases"), Novartis employees describe how knowledge of pathogen and host genomes can be used to identify and select vaccine targets in a process known as reverse vaccinology.

As proof of this concept, the authors describe how whole-genome sequencing led to the identification of vaccine-candidate antigens against Neisseria meningitidis serogroup B. An 18-month analysis of the bacterial genome ultimately led to the identification of 570 genes that likely encoded surface-exposed or secreted proteins—more vaccine-candidate antigens than those discovered during 40 years of conventional analysis. Further antigen screening resulted in the development of a "multi-component" recombinant vaccine (Novartis's MenB vaccine), which is in phase 2/3 development.

A "potentially significant" mutation of the 2009 H1N1 virus has been detected in 3 severe cases (including 2 fatalities) of pandemic flu in Norway; however, the mutated virus is nothing new, according to the World Health Organization. The spontaneous mutation—which does not confer resistance to the antiviral drugs oseltamivir (Tamiflu; Roche) or zanamivir (Relenza; GSK)—was detected as early as April and has been found sporadically in both severe and mild flu cases in other countries,* reports WHO.

The 2009 H1N1 mutation has not been described or labeled explicitly in news reports. But according to a quoted Norwegian health official, the mutation "makes it possible for the virus to fasten itself or infect deeper into the bronchioles, and therefore provide for a more serious progress of the disease." This description suggests that the mutation lies in the gene encoding the viral binding protein, hemagglutinin.

WHO maintains that the current pandemic flu vaccine does produce immunity against the mutated virus.

* Namely Brazil, China, Japan, the Ukraine, and the United States.

Depiction of H1N1 virus from Wikipedia.

And I write the title of this post without qualifying it with a phrase like "in my opinion."

The dramatic "Inside Edition" video can be found here; but any neurologist worth his or her salt would recognize that the young woman's filmed condition is factitious. I fully suspect that the Hopkins neurologists who reportedly made the diagnosis of "dystonia" believe that it represents a profound case of malingering also.

Jennings claims that her movement disorder appeared 10 days after getting a seasonal flu shot in August—so the obvious secondary gains would appear to be attention and financial compensation.

Other bloggers, like Orac and neurologist Steve Novella, have commented extensively on this case.

For the record, Jennings appears to have recovered with questionable treatments from the questionable Rashid Buttar, a controversial osteopath in North Carolina. God knows, she couldn't have kept it going forever.

11/24/09 update

Two Losers Find Each Other Thanks to a Third Loser

Jenny McCarthy's Generation Rescue evidently recommended Buttar to Desiree Jennings, the Washington Redskins cheerleader ambassador (whatever the hell that is). According to this recent Fox News affiliate report (which, once again, demonstrates that local news reporting simply sucks), Buttar diagnosed Jennings with something he calls "acute viral postimmunization encephalopathy" and "secondary mercury toxicity"—both of which he attributes to the flu shot.

But if Jenning's vaccination delivered any mercury,* she would have received no more than 25 micrograms of ethylmercury in the form of the preservative thimerosal.

And all injected seasonal flu vaccines contain inactivated (ie, split) virus, which is incapable of causing infection.

* And if the vaccine was in the form of a single-use syringe, it did not have ethylmercury-containing thimerosal.

Using a model to account for the underascertainment of cases, the CDC now estimates that 14-34 million Americans were infected with the pandemic influenza virus between April and October 17, 2009. The Center previously estimated the number of US cases between April and July 23rd of this year at 1.8-5.7 million.

A breakdown by age (years) shows that pandemic flu has preferentially affected younger adults and children. (The graph provides midlevel estimates of cases [horizontal bars] and estimated ranges [vertical bars].)

By using the CDC's midlevel estimates, the mortality rate of pandemic flu is 0.018%—which is consistent with the range of mortality rates provided by Harvard epidemiologist Marc Lipstich (0.007%-0.045%).

One of the latest apparent victims of pandemic flu is University of Ottawa chemistry professor Keith Fagnou, 38, an otherwise healthy father of 3 children. Fagnou died of suspected H1N1 disease on November 11, 3 days after being hospitalized.

HT: In the Pipeline.

Brief answer: None.

Longer answer: Recent surveillance data from 356 adults in 8 states indicate that the likelihood of contracting pandemic flu is unaffected by receiving a seasonal flu vaccine. Results of the data analysis are available in the latest issue of MMWR.

After adjusting for age and chronic medical conditions,* the CDC found that the overall effectiveness of the seasonal flu vaccines against contracting pandemic flu was -10%, with a wide 95% confidence interval (CI) straddling zero (-43%, +15%). Data were obtained during the period from May to June of this year.

These epidemiologic data complement known serologic (laboratory) data, which suggest that the trivalent seasonal flu vaccines are unlikely to provide meaningful cross-protection against pandemic flu. Likewise a recent Australian study showed that, in children or adults who received seasonal flu vaccines, cross-reactive antibodies against pandemic flu were not produced. The overall age-adjusted effectiveness of the seasonal flu vaccines against pandemic flu in this study was 3% (CI: -56%, +40%). An unpublished study of high schoolers in New York City also suggests no protective benefit of seasonal flu vaccines against pandemic flu.

However, these data are at odds with those from a recently published Mexican study, which reported a seasonal flu vaccine effectiveness rate of 73% against pandemic flu. But control patients in this study were more likely to have chronic medical conditions—making seasonal flu vaccine coverage more likely in this group. Unpublished data from Canada suggest that "medically attended" pandemic flu may actually be more likely in recipients of the seasonal flu vaccine.

The MMWR editors advise that studies with more rigorous designs and methods are currently under way to evaluate any immunity conferred by seasonal flu vaccines against pandemic flu.

* Which increase the risk of influenza-related complications (eg, heart disease, asthma, diabetes, cancer).

The number of doses of seasonal flu vaccine that were manufactured for this year, 114 million, is slightly higher than the number made last year, and about 90 million doses have been shipped so far, reports the NYT. But the shipped supply has nearly been consumed, with an estimated 85 million shots administered to date (which is about 24 million more than the number given out by this time last year). Manufacturers cannot make more seasonal flu vaccine, because they are committed to producing the pandemic flu vaccine.

Among the 5 FDA-approved vaccines for seasonal flu, a total of 248 lots have been released. (But how many packages or doses in a lot is unclear. The numbers may also vary, depending on the manufacturer or distributor. If lot numbers are uniform, then 1 lot represents about 46,000 doses [114 million divided by 248].)

1 dose = 0.5 mL, unless otherwise indicated.

Except in the case of Flumist,* the seasonal flu vaccines contain the following inactivated viruses:

• A/South Dakota/6/2007 (H1N1) (an A/Brisbane/59/2007-like virus)
• A/Uruguay/716/2007 (H3N2) (an A/Brisbane/10/2007-like virus)
• B/Brisbane/60/2008

* Flumist contains the attenuated viruses.

N.B.--The NDC contains an initial 5-digit labeler code, which is assigned by the FDA, and a 3- or 4-digit product code, which is assigned by the drug firm.

The issue of whether children with inborn errors of metabolism (IEM), like mitochondrial disorders, are more susceptible to vaccine-related adverse events was explored by combing data from the vast Northern California Kaiser Permanente electronic medical-record system. Results of the investigation were presented Friday by Kaiser physician Nicola Klein at the annual meeting of the Infectious Diseases Society of America ("Evaluating immunization rates and safety among children with inborn errors of metabolism." Abstract 187).

Klein and her colleagues found no difference in the up-to-date vaccination rates of 79 infants who had IEM and those of 1580 matched, healthy infants.** In addition, vaccination was not delayed during the first year among infants with IEM.

By using data from 322 children with IEM who received any vaccine, Klein et al also found no difference between the rates of ER visits and hospitalizations during the 30 days after vaccination and the same rates on postvax days 31-60. The rationale for the comparison was clarified by Klein at MedPage Today: "If the vaccine was causing any problems, we would expect to see them emerge right around the time of vaccination, not a month later."

MedPage Today also indicated that "children with [IEM] were not more likely than normal children to visit emergency rooms or need hospital care after vaccination"; however, this important finding (if correctly reported) was not included in the meeting abstract, nor was it elaborated by the medical news source.

* Although Poling's mother has implied that the vaccines caused the girl's mitochondrial disorder, a belief that contradicts a general understanding of inborn errors of metabolism and her neurologist father's explanation.

** Up-to-date vaccination rates were assessed at 2 years of age. Subjects were members of the Kaiser system from birth to the age of 3 years during the time period from 1990 to 2007.

HT: MedPage Today.

Update: In an e-mail, Dr. Klein confirms that her study compared ER visits and hospitalizations for the 2 time periods (within 30 days postvax and from 31 to 60 days postvax) only among children with IEM. She further advises that a comparison of ER visits and hospitalizations between healthy children and children with IEM is not appropriate, because the 2 populations are too dissimilar. Children with IEM would be expected to have "higher background rates of ER visits and hospitalizations" than healthy children.

From 1.8 to 5.7 million Americans experienced symptomatic swine flu (2009 H1N1 pandemic influenza) between April and July 23rd of this year. This estimate is based on a "probabilistic multiplier model" that adjusts for the underascertainment of pandemic flu cases in the United States. The results of the model, which was created and applied by investigators at the CDC and the Harvard School of Public Health, are available in an expedited article in the journal Emerging and Infectious Diseases.

The probabilistic multiplier model was used to adjust for the underascertainment of pandemic flu cases at each of the following steps (as diagrammed in the provided figures): the pursuit of medical care; the collection of specimens from persons seeking medical care; the submission of specimens for confirmatory testing (ie, RT-PCR); the laboratory detection of the 2009 H1N1 virus; and the reporting of confirmed cases. The model was adjusted separately for hospitalized patients (B)—who, by definition, had already sought medical care.

On the basis of the model, investigators conclude the following for the time period between April and July of this year:

• Every reported case of pandemic flu represents 79 total cases (90% probability range, 47-148).
• The estimated median number of symptomatic cases is 3.0 million.
• The estimated incidence of pandemic flu in persons ≥65 years of age is 107/100,000.
• The estimated incidence of pandemic flu in persons 5-24 years of age is 2196/100,000.
• Every hospitalized case of pandemic flu represents 2.7 total hospitalized cases (90% range, 1.9-4.3)
• The estimated median number of hospitalizations is 14,000 (range, 9000-21,000).
• The estimated ratio of hospitalizations to total symptomatic cases is 0.45% (90% range, 0.16%-1.2%).
• The estimated median incidence of hospitalizations in persons <5 years of age is 13.0/100,000.
• The ratio of deaths to hospitalizations was 6%.* (Note: This value was not derived from the model).
• The estimated median number of deaths is therefore 800 (90% range, 550-1300).

"Because this [death] assumption has several limitations," the authors conclude, "more sophisticated models are also being developed to better understand the severity of the US epidemic in the spring of 2009, including intensive care unit admissions and deaths."

RT-PCR = reverse transcriptase polymerase chain reaction.

* Therefore the overall estimated death rate (although this value is not provided in the article) is 0.027%—which is within the range provided by one of the authors, Harvard epidemiologist Marc Lipsitch, to Reuters in September.

Update: From the AP by way of the CDC—At least 114 American children have now died of complications due to the 2009 H1N1 virus. 

Among the reasons for not vaccinating their children against the seasonal or 2009 H1N1 flu, 52% of moms indicated that their pediatrician "left it up to them." Other reasons for not vaccinating included the misperception that 1) healthy children do not need to be vaccinated (63%) and 2) there are other similarly effective ways to avoid influenza (57%).

Carol Baker, MD, chair of NFID's Childhood Influenza Immunization Coalition and professor of pediatrics at Baylor, called this kind of thinking among parents "magical" or "wishful" and concluded, "[T]he survey reveals the need for more disease education and for health care providers to emphasize to parents that immunization is the best way to prevent flu."

Notably a minority of respondents expressed reservations about the effectiveness (11%) or safety (7%) of influenza vaccinations and their capacity to cause disease (5%).

The survey of 500 US mothers was conducted by telephone during August 19-25 of this year. Respondents were required to have children from 6 months to 18 years of age living with them. The reported margin of error for the survey is 4.4%.

A nonprofit organization, the NFID established the Childhood Influenza Immunization Coalition in 2007 to increase awareness of pediatric influenza and the benefits of immunization. The Coalition is funded by an unrestricted, educational grant from sanofi pasteur, one manufacturer of both seasonal and 2009 H1N1 vaccinations.

* 91% of mothers were concerned that their whole family would become ill if a child contracted seasonal flu.

It's crucial to remember that association does not mean causation. In the former case, the media jumped the gun before knowing the autopsy results. The 14-year-old English girl died of a previously undiagnosed, malignant "chest tumour." However, the nature of the link between Gardasil and the 2 ALS-like—or more accurately motor-neuron—cases remains unclear for now.

One of the motor-neuron cases, that of 15-year-old Jenny Tetlock, is commemorated at her parents' blog, Jenny's Journey. Some details of the girl's case history are also provided here.

Jenny developed leg weakness in May 2007, about 2 months after she received her third Gardasil injection. Her clinical course was, to say the least, rapid, despite "aggressive immunosuppression"—which included high-dose corticosteroids, plasmapheresis, intravenous immunoglobulin, and cyclophosphamide. A demyelinating polyneuropathy was initially suggested by nerve-conduction studies. An inflammatory component was suggested by imaging and spinal-fluid studies. Other entertained diagnoses during Jenny's unusual clinical course included spinal muscular atrophy, progressive muscular atrophy, and multifocal motor neuropathy. Suffice it to say, her clinical picture did not fit snugly into any one of these disease categories.

Jenny became quadriplegic within a year. Her clinical picture was also atypical for ALS, a purely motor disease, in that she experienced sensory symptoms. A sural nerve biopsy revealed mild axonal degeneration; demyelinating features were not prominent. Jenny died on March 15, 2009, of respiratory failure. Her autopsy revealed loss of motor neurons and marked inflammation throughout the spinal cord—an additional finding that is uncharacteristic of ALS.*

Clinical features of the other motor-neuron case, that of a 20-year-old woman, were similar. Motor symptoms began within 4 months of the first Gardasil injection; death occurred 28 months later.

A recent review of the Vaccine Adverse Event Reporting System (VAERS) revealed no similar cases linked to Gardasil, according to the reporting physician, Catherine Lomen-Hoerth, Director of the ALS Center at the University of California, San Francisco. She and her colleagues will examine the pathologic features of young adults with motor-neuron disease who did not receive Gardasil and compare these with the recently reported cases. Similar findings would argue against a causal Gardasil connection.

Juvenile ALS, which by definition begins before the age of 25 years, is generally thought to be a disease that is distinct from adult ALS. The juvenile condition is, comparatively, slowly progressive—possibly because younger patients have more neurologic reserve. Juvenile disease is almost always familial and usually autosomal recessive. Gene culprits have been identified in a minority of these rare cases, however. (Hereditary or genetic data from the 2 Gardasil-associated cases were not provided in medical news reports.) Juvenile ALS affects 1 in every 2-3 million young persons.

More than 7 million have received Gardasil, according to news reports.  

ALS = amyotrophic lateral sclerosis.

* Other atypical clinical features include 3 epileptic convulsions during illness and no upper-motor-neuron signs (eg, hyperactive reflexes). Jenny's history is notable for some developmental delay and a rare, autoimmune skin disorder. Family history does not appear to be particularly contributory.

New sources: WebMD; DocGuide.

Some kind of solace is what the otherwise rational Bill "All-I'm-Saying-Is-That-We-Should-Have-a-Debate" Maher must be seeking in his faith-like embrace of anything that's not "Western medicine"—a term that he has used liberally, disparagingly, and without explanation on his HBO show.* On the show's season finale, Maher once again maligned vaccination to an otherwise incredulous guest panel of Chris Matthews, Alec Baldwin, and Maryland Governor Martin O'Malley. Among the many illogical, non-sequitor, and/or flat-out wrong claims made by the host is this gem.

I also would like to say that I do understand the theory of inoculation. Yes, you give someone a little bit of the disease, and it fools your body into providing antibodies, which fight it. Brilliant. Bravo. Maybe there's some occasions where an inoculation is a wise thing to do. I hope not. I hope I would never have to have one, because, you know, to present it just as this genius medical advancement—no, it's actually a risky medical procedure that begs long-term cost-benefit analysis. I mean, if you don't believe me, look on the CDC web site as to what is in the swine-flu vaccine. You know, aluminum, insect repellant, formaldehyde, mercury. You know, that's right on their web site. Don't take it from a talk-show host.

Maher's last statement is the only one worth heeding. He continues to require education about the actual process of modern vaccination, given his statement "you give someone a little bit of disease...," and wrongly implies that vaccine advocates deny any risk whatsoever from vaccination.

As Maher indicates, the CDC web site offers some answers to FAQs about the ingredients of the 2009 H1N1 vaccine. The most obvious relates to the vaccine's mercury content, which has been falsely associated with the risk of autism. The truth of the matter: Only vials of the vaccine, not the prefilled syringes, contain measurable (but very tiny) amounts of ethylmercury (25 microg/dose), which is part of the thimerosal preservative. The seasonal flu vaccine is also available in thimerosal-free versions.

Data on other purported 2009 H1N1 vaccine ingredients, or lack thereof, are more easily found from online sources other than the CDC web site, including the FDA web site. Aluminum hydroxide is evidently used as an adjuvant in the low-dose Chinese vaccine,** but the US vaccine does not contain it.

Formaldehyde is used during vaccine production—to harvest and inactivate the cultivated virus from the chicken-egg medium, specifically the allantoic fluid. The virus is then chemically split by using a noninonic surfactant, polyethylene glycol p-isooctylphenyl ether, or Triton X-100. According to the package insert for the sanofi-pasteur 2009 H1N1 vaccine, "Each 0.5 mL dose may contain residual amounts of formaldehyde (not more than 100 microg), [Triton X-100] (not more than 0.02%), and sucrose (not more than 2.0%). It's not clear to me if the "insect repellant" that Maher refers to is supposed to be Triton X-100 or some other substance.

* The alternative, logically, is Eastern medicine--which is generally understood to encompass any idea of illness or medical therapy that's unproven. Adherence to Eastern medicine therefore requires faith. It could be said that Maher, who famously eschews religion, ironically places a religious-like faith in the benefits of these non-evidence-based ideas and practices.

** Hey Bill Maher, you still like Eastern medicine?

In addition, the 2009 H1N1 strain appears to be more fastidious than typical seasonal influenza viruses, requiring 2 eggs instead of the usual one to produce a single vaccine dose. Therefore 240 million eggs are needed to make 120 million vaccine doses. According to Commercial Chicken Meat and Egg Production (only $279.20 at Amazon), 1 chicken can pound out about 300 eggs annually.* If so, 800,000 chickens can produce the required number of eggs for the US supply of the 2009 H1N1 vaccine in 1 year. The AP reports that more than 30 US farms, representing 9-12 million chickens, are under long-term contract to provide eggs for vaccine production.

Alternative methods for viral cultivation, including growth in mammalian or insect cells, are evidently being explored by industry through multimillion-dollar federal contracts.

* Dunno if the rate applies equally to unfertilized and fertilized eggs.

Nevertheless, the general sentiment: One tweaked outcome is better than nothing—at least when it comes to HIV prevention.

Comprehensive results of the trial, including those for the primary endpoints of HIV infection and early HIV viremia, are tabulated here. The ITT analysis accounts for all subjects who underwent randomization; the per-protocol analysis includes subjects who received the vaccination series within the defined time period and who were not found to be infected with HIV at baseline.

* P = .09, vaccine vs placebo. 

The trial was randomized, double-blind, and placebo controlled. Four "priming" injections of a recombinant canarypox vector vaccine (Alvac-HIV; sanofi-pasteur) were followed by 2 booster shots of a recombinant glycoprotein-120 subunit vaccine (AIDSVAX; Global Solutions for Infectious Diseases) in adults aged 18-30 years. The prime-boost vaccination series was chosen on the basis of previous trials (Belshe et al, 1994; Russell et al, 2007; and AIDS Vaccine Evaluation Group 022 Protocol Team, 2001). Subjects were primarily at risk of HIV infection through heterosexual contact. After the 6-month vaccination series, enrollees were monitored for HIV infection and viremia every 6 months for 3 years.

Data regarding the potentially protective benefit of male circumcision were evidently not collected, but expect a good number of post-hoc subgroup analyses.

HIV = human immunodeficiency virus.

Like white on rice, rational bloggers have been all over Bill Maher's goofy ideas about vaccines and vaccination. It's too bad, though, that the man has a nationally televised show, HBO's "Real Time With Bill Maher," which affords Maher an opportunity to influence potentially gullible viewers in front of (like many a talk/variety/comedy show) an audibly fawning studio audience.

Nevertheless, begrudging props may be given to Maher for inviting retired Republican Senator and physician Bill Frist on Friday to discuss vaccination. In this segment, it's not entirely clear that Maher "gets schooled" by Frist about vaccines (despite the clip's title). Schooling requires that Maher's thick skull be penetrable. And schooling requires time—much more time than television typically allows.

But a blog provides an enduring, leisurely format for dissecting and refuting some of the utterly fallible anti-vaccine statements that Maher made on Friday and that Frist didn't have the chance to challenge.

Maher comment #1: Conservatives always say, about healthcare especially: You gonna let the government run healthcare? They screw everything up. So why would you let them stick a disease into your arm? I would never get a swine flu vaccine or any vaccine. I don't trust the government, especially with my health. [Applause.] And that seems to be a conservative opinion: not to trust the government.

Dissection: The usually liberal Maher tries to create a bit of oh-gosh irony here by aligning himself with traditionally government-distrusting conservatives. He then jumps to make a very broad and loose association between government incompetence and government-recommended vaccination. However, if Maher were familiar with the monumental benefits of historical vaccination programs (eg, against smallpox and polio), the association actually supports organized intervention into healthcare (whether instigated by a government or some other authoritative entity, like the World Health Organization).

At the same time, Maher indicates that vaccination is a process whereby "disease" is injected into the body. First "disease" is a clinical manifestation of bodily dysfunction; it is not something that can be confined in a syringe. But we sort of know what Maher's means here, so we'll give him a pass on this semantic point. What Maher is really implying is that disease-causing virus is injected during vaccination. But that idea is also false.

With respect to the injected 2009 H1N1 (swine flu) vaccine, the inoculant is a killed (actually chemically "split") virus—which is incapable of causing infection (but is capable of inducing protective immunity). The nasal-spray vaccine from MedImmune contains live, attenuated H1N1 virus. The attenuated virus is engineered (ie, cold adapted and temperature sensitive) so that it can replicate in the cooler confines of the nose to induce immunity, without causing influenza-like illness.

Maher indicates that he would never get the swine flu vaccine, which is fine (assuming that Maher isn't at baseline risk for influenza complications and doesn't care for an infant younger than 6 months of age*). The 53-year-old isn't a CDC-recommended candidate for the 2009 H1N1 vaccine (although he should get a seasonal flu shot).

Maher comment #2 (in response to a Frist anecdote about a patient dying of swine flu): I cannot believe that a perfectly healthy person died of swine flu. That person was not perfectly healthy. Medical—Western medicine misses a lot.

Dissection: Maher's just flat-out wrong here. Regardless of what he believes, serious H1N1-related disease preferentially affects persons younger than 65 years of age, and about 45% of Americans who have died of swine flu were healthy, according to the CDC. With his last sentence, Maher also betrays a broad, inherent distrust of Western (really, allopathic) medicine. 

Maher comment #3: Let me read you a quote from the former control officer at the US FDA. His name is Dr. J. Anthony Morris. He said, "There is no evidence that any influenza vaccine thus far developed is effective in preventing or mitigating any attack of influenza. The producers of these vaccines know they are worthless, but they go on selling them anyway."

Dissection: By quoting J. Anthony Morris, Maher reveals a lazy reliance on an ostensibly authoritative source, about which he probably knows nothing. 

Finding reliable information on Morris (at least on the web) is a challenge; at first blush, he appears to be a quotable favorite among anti-vaccinationists—probably because of the specious appeal-to-authority angle (ie, Morris reportedly has/had a PhD in bacteriology and was an FDA employee). An archived newspaper search reveals that Morris was a virologist in the Division of Biologic Standards, which was part of the NIH until 1972 when the division was transferred to the FDA.

In the fall of 1971, Morris made news by arguing to Congress that influenza vaccines were not just useless, but dangerous (see Lyons RD. Influenza shots held ineffective. NYT. October 15, 1971). He claimed that "not only has there been little or no benefit from the use of influenza vaccine in man, but harm has resulted." However, a federally appointed, 12-person scientific committee rejected Morris's claims of incompetence within his NIH division; although the committee did concede, in ho-hum fashion, that "inactivated influenza vaccines are imperfect instruments for the prevention of influenza." (The committee may have been referring to subpotent lots of influenza vaccine that were distributed in the 1960s.) The committee then proceeded to reject Morris's claims that influenza vaccines are harmful (see Lyons RD. Charges of poor vaccine regulation rejected. NYT. November 30, 1971).

A related news story in June 1972 indicates that Morris had been demoted within his division, which was now (presumably) a part of the FDA. But later news reports indicate that Morris was appointed director of the Slow and Temperate Virus Branch of the agency.

In July 1976, Morris, then 57, was finally fired from the FDA for "insubordination" and "inefficiency." Morris claimed that he was sacked from his $35,000-a-year job because he opposed President Ford's swine flu vaccination program. FDA officials acknowledged, at the time, that it was very unusual for an FDA employee to be fired, but the process that led to Morris's departure began long before anybody recognized the swine flu threat. Later Morris showed up on fear-mongering talk shows like "Phil Donahue" and provided anti-vaccine quotes to news reporters as recently as 1988. 

A phrase search of various archived newspapers fails to return a source for the exact quote cited by Maher, except in 1 instance: Donald Harte, in a November 2007 editorial for the Marin Independent Journal ("Is there a vaccine that protects against non-science?") requotes Morris from a citation in a contemporary issue of Health & Fitness magazine. The quote was described as being 30 years old, but the original source was not identified. 

Morris, if alive this year (and I haven't been able to confirm whether he's alive or dead), would be about 90. 

Maher comment #4: But a virus is always mutating. You would agree with that? [Frist: Yeah.] So, so the vaccine that they produce back in March—that's not really what's gonna prevent what's, what's going on now. Because—I know a lot of people on the conservative side don't believe in evolution—but—and you can't see evolution in advanced species, but you can see—[Frist interrupts: We know this vaccine is 98% effective...]

Dissection: Here Maher tries to discount the efficacy of the swine flu vaccine by implying that the virus has mutated so much since the creation of the vaccine (in March) that it will evade whatever immunity is produced by inoculation. However, on October 9 (the same day that Maher's show aired), the CDC reported that the 2009 H1N1 viruses "have not undergone substantial antigenic change since they were first characterized in April 2009 and should be well-matched to the monovalent vaccine strain." 

Last month, data published in the NEJM indicated that significant antibody titers were generated in 97% of adults after 1 dose of the inactivated vaccine. Rates of antibody production among children aged 6-35 months, 3-9 years, and 10-17 years were 25%, 36%, and 76%, respectively. These data are the foundation for recommending 2 vaccine doses in children younger than 10 years of age. The suboptimal immune response in younger children is probably related to their limited immune experience with influenza viruses and is clearly not the result of viral mutation.

There have been scattered reports of 2009 H1N1 virus that is resistant to oseltamivir (Tamiflu), but all of these isolates were susceptible to zanamivir (Relenza).

Maher comment #5: Dr. Jonas Salk: "Live virus vaccines against influenza and paralytic polio, for example, may in each instance cause the disease it's intended to prevent."

Dissection: Another appeal to authority by Maher. Salk, as everyone knows, was the creator of the inactivated polio vaccine. The quote cannot be confirmed and, again, appears to be a favorite among online anti-vaccinationists. An archived newspaper search fails to return relevant hits, and without context, it's useless to interpret a statement that Salk may or may not have made.

* And don't we all hope that's the case.

A simplified table of the FDA-approved vaccines against the 2009 H1N1 virus is provided here, with a focus on age and dose recommendations. For complete data, see this week's MMWR.

The IM shots contain inactivated virus, and the nasal spray (from MedImmune) contains attenuated virus. Prefilled syringes do not contain mercury (that is, 25 microg Hg per 0.5 mL of vaccine, in the form of thimerosal preservative). When 2 doses are recommended, they are administered approximately 4 weeks apart.

The nasal spray vaccine is indicated for healthy, nonpregnant persons aged 2-49 years and should not be administered to persons with asthma. The dose of the nasal spray is divided equally between each nostril.  

Note: These data are for informational purposes only and should be confirmed by referring to authoritative sources (eg, the CDC) and/or a treating healthcare professional.

* Latter approved by FDA for age group on 11/12/09.

Pneumococcal vaccines, which can protect against influenza complications, are underused. And there is no shortage of these vaccines. These facts were relayed by Thomas Frieden in today's CDC press conference.

The CDC recommends the PCV7 vaccine (Prevnar; Wyeth) routinely for children younger than 2 years of age (1 dose each at 2, 4, 6, and 12-15 months) and older children who have not completed the 4-series vaccination.

The CDC recommends the PPSV23 vaccine (PneumoVax; Merck) for all adults aged 65 years or older and any individual 2-64 years of age with a long-term health problem (eg, diabetes) or a condition that lowers resistance to infection (including therapy). The CDC also recommends the PPSV23 vaccine for adults 19-64 years of age who smoke or have asthma.

Pneumococcal immunization protects against infection with Streptococcus pneumoniae, the most common bacterial pathogen in reported fatal cases of H1N1 infection to date.

For authoritative and comprehensive information on this subject, see the CDC web site.

PCV7 = 7-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine.

Photomicrograph of S. pneumoniae grown from blood culture from the CDC/Dr. Mike Miller.

And no state remains unaffected.

The CDC advises, however, that heightened H1N1 activity does not reflect the severity of disease. At least 99% of all subtyped influenza virus samples (n = 1402) are the 2009 H1N1 virus.

Also according to CDC data, the in-hospital death ratio associated with influenza-like illness (ILI), as of September 19, was 0.093 (mortality rate, 9.3%). US deaths include 49 children.

Multiplying the US hospitalization ratio for April 15 to July 24 (0.114) by the CDC's latest in-hospital death ratio for ILI provides a case-fatality ratio of 0.0106 (mortality rate, ~1%). However, a Harvard epidemiologist recently estimated the H1N1 death rate to be considerably lower—from 0.007% to 0.045%.

Vaccines for the 2009 H1N1 virus are expected to be available next month (that is, in a few days), with the nasal-spray vaccine preceding the shot vaccine in the US marketplace. Candidates for the nasal vaccine are nonpregnant persons 2-49 years of age.

Newly released results from a national survey (N = 1678), performed by the University of Michigan in August, revealed that a minority of parents plan to have their children vaccinated against the pandemic H1N1 virus. (The CDC currently recommends that all individuals from 6 months to 24 years of age undergo H1N1 [swine flu] vaccination.) Surveyed parents reported that they are more likely to have their children receive the seasonal influenza vaccination.

Parents' perception of the risks associated with H1N1 flu were closely linked to the likelihood of opting for the vaccine. Notably Hispanic parents were more likely to report their intention of having their children undergo vaccination—possibly because they perceive a higher threat from the disease than non-Hispanic parents. For instance, Hispanic parents may be more aware of the recent history of H1N1 disease in Mexico.

That's because...

The injected vaccine for seasonal influenza was more effective at inducing immunity than the nasal-spray version in adults, according to a study published yesterday in the NEJM. The results can possibly be applied to vaccine options for pandemic H1N1. (But then again, maybe not. Read on.)

In a randomized, double-blind, placebo-controlled study of 1952 healthy adults (18-49 years of age) during the 2007-2008 influenza season,* the injected vaccine (which contains inactivated virus) reduced the relative risk of laboratory-confirmed influenza by 50%, when compared with the nasal-spray vaccine (which contains live, attenuated virus). The rates of absolute efficacy against influenza A (predominately the H3N2 virus) were 72% and 29% for the shot and spray vaccines, respectively.

Other data indicate, however, that the spray vaccine is more effective for the prevention of flu than the injection in young, vaccine-naive children (2 doses) and in older children (1 dose).

It is speculated that the nasal-spray vaccine is relatively less effective in adults, because preexisting seasonal flu antibodies thwart the vaccine antigens at their entry point in the nasal passages. But because the pandemic H1N1 virus is new to everybody, the nasal-spray vaccine may work comparably in children and adults.

* According to the CDC, circulating viruses during this season in the United States were influenza A (71%) and influenza B (29%). Early in the season, influenza A H1N1 viruses predominated, followed by an increase in circulating H3N2 viruses. Influenza B viruses were more common during the tail of the season. Circulating H3N2 viruses were most common overall.

********************************

And on a related note...

A high-profile anecdote of confirmed illness with the pandemic H1N1 virus was provided yesterday by CNN's Sanjay Gupta. Gupta's prominent symptoms were similar to those of seasonal flu: a hacking cough, fever, nausea, and body aches. Although Gupta reported, "[T]his was the sickest I have ever been," he recuperated after a couple of days of symptomatic treatment and bed rest. He evidently did not receive antiviral therapy (eg, oseltamivir [Tamiflu]).

Seasonal Influenza Vaccine (available now)

Who should receive the seasonal influenza vaccine?

• Individuals from 6 months to 19 years of age and individuals 50 years of age or older
• Pregnant women
• Persons with certain chronic medical conditions
• Individuals living in nursing-home or long-term care facilities
• Persons living or working with others who are at risk for influenza-related complications (eg, healthcare workers, daycare employees).

Who is a candidate for the intranasal spray vaccine, which contains 3 live, attenuated seasonal influenza viruses?

Healthy, nonpregnant persons 2-49 years of age.

Who is a candidate for the intramuscular vaccine, which contains 3 inactivated seasonal influenza viruses?

Children 6-35 months of age (dose, 0.25 mL) and individuals 3 years of age or older (dose, 0.5 mL).

Who should receive 2 doses of the seasonal influenza vaccine (each separated by 4 weeks)?

Children younger than 9 years of age who 1) are receiving the seasonal influenza vaccine for the first time or 2) received the vaccine for the first time during the previous influenza season and received only 1 dose.

Pandemic H1N1 (Swine Flu) Vaccine (expected in October)

Who should receive the swine flu vaccine?

• Pregnant women
• Persons who live with or care for infants younger than 6 months of age
• Healthcare and emergency medical personnel
• Persons aged from 6 months to 24 years
• Individuals aged 25-64 years who are at risk for influenza-related complications (eg, persons with asthma, diabetes, hypertension, HIV). 

Who is a candidate for the intranasal spray vaccine, which contains the live, attenuated pandemic H1N1 virus?

The same individuals who are candidates for the intranasal seasonal influenza vaccine: healthy, nonpregnant persons 2-49 years of age.

Who is a candidate for the intramuscular vaccine, which contains the inactivated pandemic H1N1 virus?

All individuals who are priority candidates for the pandemic H1N1 vaccine.*

Who should receive 2 doses of the swine flu vaccine (each separated by 3-4 weeks)?

Late-breaking data suggest that 1 vaccine dose will be sufficient to induce a protective immune response in persons 10 years of age or older. Children from 6 months to 9 years of age, however, will likely require 2 doses of vaccine.

* I suspect that doses, like those for the seasonal influenza vaccine, are cut by half for children 6-35 months of age; however, I have not yet confirmed this information.

**********************

The US Department of Health and Human Services (HHS) recently ordered 56 million more doses of the pandemic H1N1 vaccine from MedImmune and sanofi pasteur for an additional $438,143,025. The total US government spend on the pandemic H1N1 vaccine is now $2,255,120,945, which amounts to $8.98 per vaccine dose.

Last week's late-breaking data indicated that 1 vaccine dose (15 micrograms), instead of the originally anticipated 2, will be sufficient to induce a "robust" immune response in most adult recipients. The optimal dose in children, however, has not been confirmed.

The vaccines are produced by using the same methods as those for seasonal flu vaccines, including viral cultivation in chicken eggs. (WHO nicely explains the vaccine-manufacturing process here.) Consequently people with "severe or life-threatening" allergies to chicken eggs should not receive the vaccine. Vaccines will also be available in preserved (ie, thimerosal containing) and nonpreserved formulations.

Side effects of the injected and nasal-mist vaccines are anticipated to be similar to those seen with the seasonal flu vaccines.

Five companies contracted with the US Department of Health and Human Services (HHS) to create and manufacture a vaccine against the novel H1N1 virus; only GlaxoSmithKline failed to receive vaccine approval yesterday. Reasons for the delayed or deferred approval of GSK's vaccine were not provided by the FDA or the company.

According to a cached version of the web page detailing HHS's contracting activities, the following government orders for novel H1N1 vaccines were made in May and June.

HHS = Health and Human Services.

Addendum: An updated HHS web page reveals that MedImmune received a total of $151,008,000 in contracts for May and June. The cumulative government spend is therefore $1,815,977,920. With an order of 195 million doses, that's $9.31 per vaccine dose.  

Dr. Thomas Frieden of the Centers for Disease Control and Prevention (CDC) conducted this week's broadcasted press conference on the status of the novel H1N1 epidemic in the United States.

Points made.

• The bad news: Novel H1N1 virus is here and spreading, and notably, infection didn't abate during the summer ("very usual"). Expect to see more cases in the coming months.
• The good news: The virus has not mutated, as yet, to become more deadly; and so far, antiviral-resistant strains of H1N1 have not been observed. (See Addendum.)
• The caution: But influenza is unpredictable, and readiness for the worst is imperative.
• The verified data:
  a) There have been 36 pediatric deaths in the United States, details of which are in the latest issue of the MMWR; children with special needs appear to be particularly vulnerable to infectious complications, including death.
  b) Recent experience in the Southern Hemisphere (5 countries) is similar to that in the United States (during the Spring); there have been hospitalization challenges but no increase in the H1N1-related death rate.
  c) The Institute of Medicine (IOM) issued a report today recommending fitted N95 respirators, instead of the typical face mask, for healthcare workers who interact with H1N1-infected patients.*
• The unverified data: A 1-dose vaccine, which was recently approved in China.
• The 2-dose vaccine:
  a) Still expected in mid-October.
  b) To induce effective immunity, 2 doses are anticipated to be necessary.
  c) Recommended groups for vaccination remain the same.
  d) The vaccine itself is free, although administration may not be; the government is in the process of releasing $1.5 billion to enable/facilitate vaccine administration.
  e) Vaccination programs will be run on the local level (eg, state). 
• The upcoming surveillance: For possible adverse events (eg, Guillain-Barre syndrome, miscarriages) associated with vaccination.
• The challenge to safeguard healthcare resources:
  a) Most cases of novel H1N1 infection are mild and don't necessitate laboratory testing or antiviral treatment.
  b) Stay home if you're sick.
  c) Cover your face when coughing or sneezing.
  d) Wash your hands.
  e) Don't go to the doctor unless you're severely ill or have an underlying condition (although it's important to be seen promptly in these cases, so that antiviral therapy can be instituted in a timely fashion [ie, within 48 hours of symptom onset]).
  f) To employers: Don't require a permission note from an employee's doctor before the employee can return to work; in general, telecommuting may be a good idea.

* The IOM was not charged with considering cost, when making its recommendation.

Depiction of H1N1 virus from Wikipedia.

09/05/09 addendum: In its August 12th report, WHO indicated knowledge of 12 cases of disease that is resistant to oseltamivir (Tamiflu; Roche). The mutated virus, however, remains sensitive to zanamivir (Relenza; GSK). Oseltamivir-resistant cases occurred sporadically throughout the world and were apparently not connected. 

1. pregnant women;
2. persons who live with or provide care for infants younger than 6 months of age;
3. healthcare and emergency medical services personnel;
4. individuals from 6 months to 24 years of age; and
5. individuals 25-64 years of age who have medical conditions (eg, asthma, hypertension, diabetes, HIV) that increase the risk of influenza-related complications.

This population, in total, is estimated to include 159 million Americans, although the estimate does not account for overlap among subgroups (eg, a physician-parent with a young infant). The CDC advises that vaccination of these subgroups should begin as soon as vaccine is available.

The CDC has also identified sub(sub)groups of candidates, should the vaccine supply not meet the targeted demand:

1. pregnant women;
2. persons who live with or provide care for infants younger than 6 months of age;
3. healthcare and emergency medical services personnel who have direct contact with patients or infectious material;
4. children from 6 months to 4 years of age; and
5. children and adolescents 5-18 years of age who have medical conditions that increase the risk of influenza-related complications.

Licensed vaccines, which are expected to be available in the United States by mid-October, are necessary because the vaccines for seasonal influenza are not likely to provide adequate protection against the novel H1N1 virus.

While drugmakers create a vaccine against the currently pandemic swine-flu virus (H1N1 S-OIV 2009), neurologists are advised to monitor the safety of such inoculations, should they be implemented. The caution is founded on a higher-than-expected rate of Guillain-Barre syndrome (GBS) in vaccine recipients during the 1976 immunization campaign against swine flu, reports Neurology Today.

More than 30 years ago, soldiers at Fort Dix, New Jersey, experienced an outbreak of swine flu. Fearing a recurrence of the 1918 influenza epidemic, US government officials implemented a widespread vaccine campaign in which more than 40 million Americans were immunized. However, the drive was aborted after 3 months when reports of GBS in vaccinated individuals emerged. Although GBS surveillance data for the time period are sketchy, evidence suggests that vaccine recipients were significantly more likely to develop the condition within several weeks after inoculation.*

At present, leading neurologists do not anticipate a government-led vaccine campaign against H1N1 S-OIV 2009, given the low mortality rate (0.5%) of the current swine-flu pandemic and the historical risk of GBS with inoculation.

* The typical background rate of GBS is about 1.5 per 100,000 individuals.

Parents who refuse pertussis (whooping cough) vaccination for their child increase the child's risk of infection by about 20-fold. This conclusion is derived from a first-of-its-kind study of medical records within the huge Kaiser Permanente Colorado health plan (N > 430,000 members). Results of the study were published in the latest issue of Pediatrics.

Investigators extracted individual-level data from the medical charts of children (age 2 months-18 years) about documented vaccine refusal and pertussis infection during a 12-year-period (1996-2007). A total of 156 laboratory-confirmed cases of pertussis were discovered; 9 (6%) required hospitalization.* Among these 156 cases, the parents of 18 children (~12%) had refused all or nearly all of the recommended pertussis vaccinations.** Among a randomly selected, matched control population (n = 595), the vaccine refusal rate was 0.5%.

Two case-control analyses (primary and secondary) were used to determine the odds of pertussis infection as a function of vaccine refusal. (In the secondary analysis, subjects were continuously enrolled in the health plan between the ages of 2 and 20 months.)

Assessments of attributable risk suggested that all 18 cases of pertussis in unvaccinated children were due to vaccine refusal.

The investigators acknowledged that a potential bias in the study was the fact that physicians were 3 times more likely to test for pertussis in unvaccinated children who presented with a respiratory infection. But this bias was probably offset by the fact that unvaccinated children with a respiratory infection were less likely to present for evaluation than vaccinated children. 

* Notably the annual incidence of confirmed pertussis cases increased over time; more than three quarters occurred after 2001.

** The parents of 14 children had refused all routine immunizations. Most of these parents were white, older than 30 years of age, and of higher socioeconomic status.

Photo of symptomatic child with pertussis from pertussis.com.

Neither reviewer addressed my concerns about the specific metabolite values of Geier et al nor the possibility of subject overlap in a similar Neurochemical Research article; however, Reviewer #1 chided the authors for not providing norms for laboratory values, if available. Reviewer #2 expressed concerns with the authors' lack of intra-assay standards when measuring urinary porphyrins, how these values compare with those from normal controls, and sample collection (both blood and urine). Information regarding control subjects—such as the exact number, gender breakdown, and reasons for testing—were also lacking. Both reviewers stated that Geier et al should have matched subjects and controls for age and sex, when analyzing their results.

Both reviewers also suggested that Geier et al were far too eager to ascribe their results (specifically the presence of urinary porphyrin metabolites) solely to mercury toxicity. They did not consider other possibilities, such as immune conditions, infection, or exposure to other heavy metals. Geier et al did not control for these factors, Reviewer #2 noted, and concluded, "The authors are clearly not objective. They continually refer to the results as indicative of exposure to mercury...not so."

* These unnamed scientists did not originally peer review the manuscript before publication.

This most recently developed theory of antivaccinationists proposes that simultaneous administration of multiple vaccines somehow affects (overwhelms, weakens, etc) a child's immune system, which in turn leads to some sort of neurologic effect that triggers autism. The big problem with this theory, as Gerber and Offit rightly note, is that there is no evidence that autism is an immune-mediated (or specifically autoimmune-mediated) disease.

Their counterarguments, with respect to vaccines:

• They do not overwhelm or weaken even a new infant's immune system—which, although immature, can generate "a vast array of protective responses."
• The total immunologic load of currently recommended vaccines (14) is actually much less than that of recommended vaccines administered in 1980 (7)—all thanks to advances in protein chemistry and DNA technology.
• Vaccines actually represent a tiny fraction of the immunologic challenges (eg, all those environmental antigens running around) that a child typically encounters.
• Vaccines don't "weaken" the immune system, as evidenced by the equivalent susceptibility to infections* among vaccinated and unvaccinated children.
• Last, there are no clinical data** to support the idea that spreading out or reducing the number of childhood vaccinations reduces the incidence of autism.

* Non-vaccine preventable.

** And for good reason, because such a study would be unethical.

Measles is unlikely to be eradicated in Europe anytime soon, according to the Euvac.net group, a surveillance network for vaccine-preventable diseases. The group's conclusion is based on the relatively high incidence of measles and the prevalence of unvaccinated or incompletely vaccinated children throughout the continent. The group's study of the persistence of measles in Europe, despite the fact that the measles vaccine became a part of routine vaccination more than 20 years ago, was published in the latest issue of The Lancet.

Recent 2-year surveillance data (2006-2007) from 32 European countries revealed a total of 12,132 measles cases; 85% occurred in 5 countries: Romania, Germany, the United Kingdom, Switzerland, and Italy. Most of those affected were either unvaccinated or incompletely vaccinated children; however, nearly 20% were adults. Measles caused the deaths of 7 children.

In 2006, 10 cases of acute measles encephalitis* (including the 2 deaths) were reported. Six of those affected had not been vaccinated; one had received a single vaccine dose; and the vaccination status was not known for the remainder. In 2007, 7 individuals, none of whom had been vaccinated, acquired acute measles encephalitis.

On the basis of these data, the group expresses "serious doubts" that measles will be eliminated from Europe by 2010, the current goal of the World Health Organisation. According to WHO, the elimination of measles requires the achievement and maintenance of a minimum 95% vaccination coverage with 2 doses of the measles vaccine. In European countries where there were no measles cases during 2006 and 2007 (Finland, Iceland, Slovenia, Slovakia, and Hungary), vaccination coverage (2 measles vaccine doses) has been historically and consistently high.

* As opposed to subacute sclerosing panencephalitis (SSPE), a rare, fatal complication of measles, which can develop years after the incident infection.

Photo of child with measles rash from the CDC.

Most important, however, is the fact that a whopping 91% of cases occurred in individuals who had not received vaccination or whose vaccination status was unknown. Among these 112 patients, 85% were eligible to receive vaccination, but 66% had declined because of "philosophical or religious beliefs." In many cases, elected exemptions are based on parents' disproven fears of the risk of autism.

In England, measles was declared endemic this year for the first time since the mid-1990s, because a critical number of parents declined vaccinations for their children. Gibraltar also experienced an unprecedented measles outbreak, which affected 1% of the population. The outbreak was blamed on the poor uptake of measles vaccination and a subsequent shortage of the vaccine.

Those most affected by the deferral of measles vaccination are immunocompromised children and children younger than 12 months of age, who rely on adequate herd immunity. It appears to be a matter of time before a measles outbreak will cause a known, severe complication of the disease, like encephalitis or death, in the United States. Such an event occurred in April in the United Kingdom.

By way of contrast, worldwide deaths due to measles dropped dramatically, according to the World Health Organisation. The plunge in measles-related deaths, from 750,000 in the year 2000 to 197,000 last year, is due to a massive, coordinated vaccination effort, the Measles Initiative. In Africa and countries of the Eastern Mediterranean region specifically, the effort resulted in a fall in measles deaths by approximately 90% during the same time period. The goal of the Measles Initiative—which is led by the American Red Cross, the CDC, the UN Foundation, UNICEF, and WHO—is to reduce the number of measles deaths worldwide by at least 90% by the year 2010.

Because the majority of measles-related deaths no longer occur in Africa, vaccination efforts are now being intensified in other regions—particularly India, where 8.5 million children do not receive their first dose of measles vaccine by 1 year of age. According to a spokesperson for the UN Foundation, the success of the campaign depends on urgently needed funds for the next 2 years.

More details can be found at the following Pathophilia links (and at links through these links):

• And the Air-Travel Risks Just Keep on Comin': This Time, Measles
• Looming Large: The Cost of Not Vaccinating
• Measles Outbreak in DuPage County, IL
• Biggest US Measles Outbreak in 10 Years
• Boo, Boo, Boo: US Measles Cases Increase
• Most US Parents Remain Sane, Vaccinate Children
• Measles Hits Gibraltar, Hard
• Global Measles Initiative a Success, but Funding Needed

* The percentage of US toddlers who received at least 1 dose of MMR vaccine (from 91.5% to 93.0%) has remained stable since 2004. Still nearly 8% of American toddlers did not receive vaccination for the disease in 2007, and geographic clusters of unimmunized children appear to account for this year's record number of cases of the highly contagious disease.

Photo of child with measles rash from the CDC.

Jayne M. Ness, MD, PhD, of the University of Alabama at Birmingham, and James F. Bale, Jr, MD, of the University of Utah, examined data from a recently published, population-based, case-control French study, which found a nonsignificantly increased risk of multiple sclerosis in children who received GSK's Engerix-B vaccine 3 years before their initial symptoms (OR = 1.68; CI: 0.92, 3.04). However, in 72 children with MS who were vaccine compliant, nearly one third had received Engerix-B vaccine more than 3 years before their index demyelinating episode (adjusted OR = 1.74; 95% CI: 1.03, 2.95).

Ness and Bale raise the possibility that this latter finding is a statistical fluke, fostered by the use of subanalyses. But, because a specific vaccine's makeup* and timing may influence the risk of immune-mediated conditions, they conclude that subanalyses in this case are justified. They stress that children with MS, in particular, "may provide invaluable insights regarding the pathogenesis of the disorder," because of the proximity of their disease onset to potential environmental triggers, like specific antigens.

It is important to note that at least 5 other retrospective or case-control studies (1999-2003) found no association between HepB vaccination and MS onset or relapse, and the US Institute of Medicine and other review panels have rejected a causal relationship between HepB vaccination and MS. While Ness and Bale acknowledge these data, they do not consider the issue of HepB vaccination and MS risk resolved. Nevertheless, they appropriately advise:

Before concluding that there may be a link between HB immunization and MS...other adult and pediatric MS populations must be studied in similar detail. If the association of MS with specific HB vaccines is substantiated, this finding may enable identification of triggers that may or may not have structural or antigenic similarities to the vaccine-associated HB antigens. In the meantime, current recommendations for widespread HB vaccination should be supported as the real risk of HB infection still outweighs the theoretical risk of developing MS.

* For instance, Engerix-B and Recombivax HB contain the recombinant 226-amino-acid S gene product of the hepatitis B major surface antigen, which is generated in cultures of Saccharomyces cerevisiae (baker's yeast). GenHevac B, which is not licensed for use in the United States or Canada, contains PreS2 and S recombinant proteins produced in a mammalian cell line.

Photo of infant undergoing vaccination from the CDC/Judy Schmidt.

Because the majority of measles-related deaths no longer occur in Africa, vaccination efforts are now being intensified in other regions—particularly India, where 8.5 million children do not receive their first dose of measles vaccine by 1 year of age. According to a spokesperson for the UN Foundation, the success of the campaign depends on urgently needed funds for the next 2 years.

* Includes Afghanistan, Pakistan, Somalia, and Sudan.

Photo of measles vaccination in Bangladesh by Daniel Cima/American Red Cross.

12/05/08 update: This week's MMWR provides additional tabulated and graphic data. In Southeast Asia, the number of measles deaths dropped from 235,000 to 136,000 (42%) during the period from 2000 to 2007. In the Western Pacific, measles deaths fell from 25,000 to 7000 (73%). The estimated number of measles deaths in the Americas or Europe is less than 1000 for all years, with vaccination coverage rates of 93% and 94%, respectively.  

The latest data were derived from a WHO surveillance program in 35 countries in Africa, Central and South America, Eastern Europe, the Eastern Mediterranean, Southeast Asia, and the Western Pacific. Detection was based on an enzyme immunoassay for rotavirus antigen in stool samples, and strain genotypes were identified by RT-PCR. The most common strains, excepting those in the Eastern Mediterranean region and Africa, were G1P[8], G9P[8], and G2P[4]—which accounted for two thirds of the strains detected.

In trials in the Americas and Europe, 2 live, oral rotavirus vaccines—an attenuated G1P[8] human rotavirus vaccine (Rotarix; GSK Biologicals) and a live, pentavalent, human-bovine (WC3 strain) reassortment vaccine containing serotypes G1, G2, G3, G4 and P[8] (RotaTeq; Merck)—conferred 85%-98% protection against rotavirus diarrhea. These vaccines have been incorporated into the routine immunization programs in 11 countries in these regions and in Australia. Trials of these vaccines in low-income Asian and African countries are ongoing. Notably these vaccines confer protection against rotavirus serotypes that have not been included in their respective formulations.

The CDC recommends 3 doses of an FDA-approved rotavirus vaccine** between the ages of 6 and 32 weeks. An interim report indicates that, for the 2007-2008 rotavirus season in America, viral activity started much later and was much less extensive than in previous years. These changes are believed to be due to the uptake of rotavirus vaccine.

According to the MMWR, more than half a million young children in the world die each year from rotavirus-induced diarrhea; 85% of these deaths occur in low-income African or Asian countries.

* Younger than 5 years of age.

** The tetravalent rhesus-human reassortment rotavirus vaccine (RotaShield; Wyeth) was voluntarily withdrawn from the market in 1999 owing to a low, but increased, risk of intussusception.

Transmission electron photomicrograph of intact rotavirus particles from the CDC.

According to the CDC, HepB coverage—especially within 24 hours after birth—is hampered in endemic areas by limited access (for instance, among infants born at home in remote areas), poor training or coordination among maternal healthcare workers, inadequate delivery of the vaccine (which requires cold storage), and the use of combination vaccines (eg, the Haemophilus influenza type b and HepB vaccine), which cannot be administered at birth. In 2006, 46% of the world's infants were born in countries where chronic infection with hepatitis B virus is historically high.

The major routes of HBV transmission in infancy include maternal transmission during delivery and infection from household contacts. The risk of developing chronic HBV disease among infected infants is very high, 90%, and the risk of premature death due to cirrhosis or liver cancer (photo) with chronic HBV is 25%, according to the CDC. Perinatal infection with hepatitis B virus causes nearly one quarter of the world's 620,000 HBV-related deaths each year.

The CDC recommends vaccination with monovalent HepB in all newborns before hospital discharge and within 12 hours of birth if the mother is positive for hepatitis B surface antigen or her status is unknown. A monovalent or combination vaccine containing HepB is administered at 1-2 months of age, and a final dose is given at 6 months of age or later.

HBV = hepatitis B virus; UNICEF = United Nation's Children's Fund; WHO = World Health Organisation.

* Defined as ≥8% in the general population and includes 87 countries: 45 in Africa; 23 in the Western Pacific; 10 in Europe; 5 in Southeast Asia; and 4 in the Eastern Mediterranean. 

Photo of Cambodian woman with hepatocellular carcinoma due to chronic HBV infection from the CDC.

Nearly 1% of Gibraltar's population has been affected by an intense measles outbreak during the last 3 months, reports the NYT. Specifically 276 cases of the disease, among a population of 28,000, are being reported by the British territory's health director. A Gibraltar news source indicates that the actual number of those infected is probably greater, given that residents with mild disease may not report their illness.

Those with measles range in age from 4 months to 58 years; however, most are children. Cases have been generally mild, but some infected individuals—including infants—have needed intensive hospital care. Gene analysis suggests that the responsible virus came from an outbreak in nearby Algeciras, Spain, a port city across the Bay of Gibraltar, writes the NYT.

The recent number of measles cases in Gibraltar stands in sharp contrast to reported cases of the disease in the territory during the previous 10 years: zero. The outbreak is believed to be due to inadequate immunization, despite assumptions that vaccination rates among Gibraltar's children were high. All infected persons had not been vaccinated or were only partly vaccinated (ie, with 1 dose of MMR vaccine) reports a Gibraltar news source. During the beginning of the outbreak, a vaccination campaign faltered twice because of vaccine shortages in Britain, according to the NYT.

Earlier this year, measles was declared endemic in the United Kingdom, after 14 years of eradication. The UK's Health Protection Agency reports a total of 956 measles cases from January to September of this year. At last count, the number of measles cases in the United States for the year was 131.

Photo of child with measles rash from the CDC.

Never been a big fan of Nancy Snyderman, but she does a good job here of talking down a persistent Matt Lauer, who insists that there's "controversy" about the link between vaccines and autism.

HT to TheProbe, commenting at "Respectful Insolence."

Despite unfounded concerns about vaccine risks among toddlers, more American teens are receiving their recommended vaccinations, including those against meningococcus and human papillomavirus, according to CDC survey results published in last week's MMWR. Increases in the receipt of delayed childhood vaccinations in adolescents—like those for MMR, hepatitis B, and varicella—are also reported.

By conducting a random survey of 2947 adolescents (age range, 13-17 years), the CDC's National Immunization Survey-Teen (NIS-Teen) discovered a statistically significant increase (11.7% → 32.4%) in the receipt of MCV4 (eg, Menactra; sanofi-aventis) from 2006 to 2007, and that approximately one quarter of adolescent girls had initiated coverage with the 3-dose HPV4 vaccine (Gardasil; Merck) last year. A slightly smaller percentage (23.5%) had received all 3 doses of HPV4 at the time of the survey.*

Coverage for recommended childhood vaccinations among the survey population is as follows.

When assessing children 13-15 years of age, the hepatitis B vaccine (≥3 doses) was received by 89.5% and at least 2 doses of MMR were received by 89.0%. These coverage rates nearly reach the DHHS targets of 90% for the year 2010.

For this year's survey, NIS-Teen will collect data from a larger population sample to examine vaccination coverage by ethnicity, socioeconomic status, and locality.

HepB = hepatitis B vaccine; HPV4 = quadrivalent human papillomavirus vaccine; MCV4 = meningococcal conjugate vaccine; MMR = measles, mumps, rubella vaccine; Td = tetanus and diphtheria toxoids vaccine; Tdap = tetanus, diphtheria, acellular pertussis vaccine; VAR = varicella vaccine.

* Routine vaccination with HPV4 is recommended for girls at the ages of 11-12 years.

Screen shot of teens lovin' the Slip 'N Slide from YouTube. Note that increase in vaccination coverage and apparent increase in Slip 'N Slide use among teens does not necessarily indicate a causal relationship; although you can't engage in backyard fun when you've been killed by infectious disease.

Hepatitis B vaccination generally does not increase the risk of pediatric CNS demyelinating diseases—like multiple sclerosis—in the short or long term; however, the Engerix B vaccine (GlaxoSmithKline) brand may, in the long term. These conclusions are based on a population-based, case-control study conducted in France, which was published online this week in Neurology. The investigators stress that their results require confirmation.

By matching 349 pediatric cases of clinical CNS demyelination—either single episodes* without relapse or MS—to 2941 controls (median control no. per case, 9), investigators calculated an adjusted odds ratio of 0.74 (95% CI: 0.54, 1.02) for an index episode of demyelination within a 3-year period of vaccination. Similar results were obtained when assessing more detailed time periods, number of hepatitis B vaccines received, and vaccine brand last received.

General rates of hepatitis B vaccination were similar in the case and control groups (24.4% and 27.3%, respectively). Notably a family history of MS was significantly higher in the case cohort (2.3% vs 1.1% in controls; P < .05); but calculated odds ratios were not significantly different when cases with a family history were excluded from analysis.

When considering cases and controls that were compliant with vaccine guidelines, exposure to Engerix B vaccine more than 3 years before the index episode was associated with an increased risk of CNS demyelination (adjusted OR, 1.74; 95% CI: 0.93, 2.43), and particularly MS (adjusted OR, 2.77; 95% CI: 1.23, 6.24). A trend toward an increased risk of CNS demyelination 3 years from the time of exposure to the GenHevac B vaccine (sanofi-aventis) was also observed in vaccine-compliant cases (adjusted OR, 1.50; 95% CI: 0.71, 3.17).

Other vaccines assessed in the study, which was supported by the Société Française de Neuropédiatrie and the French Ministry of Health, included HBVax (Vabiotech), Twinrix (GSK), and Recombivax (Merck). The authors propose that risk differences among vaccine brands may be due to the particular section of the hepatitis B surface antigen (HBsAg) used or variable reactions to yeast proteins (HBsAg is produced in yeast cells).

The prevalence of pediatric CNS demyelinating disorders is not well defined, but it is estimated that 12,000-22,000 people (2.7%-5.0%) living with MS in the United States or Canada received a diagnosis before the age of 16 years. 

CNS = central nervous system.

* Single episodes of demyelination (n = 198) included acute disseminated encephalomyelitis (ADEM), optic neuritis, transverse myelitis, and brainstem dysfunction. Cases were matched to controls for age, sex, and area of residence.

Photo of child with measles rash from the CDC.

Roger Brumback, editor in chief of the Journal of Child Neurology, is not happy. Neurologist Jon Poling, the lead author of the 2006 case report in JCN, "Developmental regression and mitochondrial dysfunction in a child with autism," did not inform Brumback's editorial board that he is the father of the girl described in the report, and moreover, that he petitioned the National Vaccine Injury Compensation Program (VICP) in 2003, claiming his daughter's alleged injury (ie, autism) was due to vaccination.

In a letter published in last month's issue of the JCN (BIG HT to Kathleen Seidel at Neurodiversity), Brumback describes the authors' lack of full disclosure "an appallingly troubling issue." The JCN editors were evidently troubled enough to determine if the case report was used to support the favorable and heavily publicized VICP ruling for the Polings earlier this year (it was not), but Brumback proposes that "media linkage of the published article to the legal outcome implies scientific support from JCN for this legal opinion." He now advises:

Beginning in January 2009, statements from all authors concerning potential conflicts of interest will be published as a part of each article. However, no written statement can substitute for honesty, good faith, and integrity on the part of the authors.

In their defense, the report's coauthors Richard Frye, Andrew Zimmerman, and John Shoffner claim in a separate letter that they did not know of Poling's pending VICP claim at the time of the report's submission to JCN. (However, it is unclear, as Seidel points out, whether the coauthors became aware of Poling's claim sometime later.) The coauthors did know that the report's subject is Poling's daughter.

Poling himself acknowledges, in yet another separate letter to the JCN, that he should have declared his daughter's identity to the JCN editors, but that he withheld her name "to protect a 6-year-old child." Poling confirms that the JCN report was not used to support the VICP claim and characterizes his involvement in the case as minimal—consisting of signing a "short original petition and submitting a required sworn parental affidavit." Poling also reveals that Zimmerman submitted an expert opinion to the VICP court in December 2007 at Poling's request.

Poling further claims, "There are certainly other physicians who have chosen not to publish promising leads or discoveries involving family members, out of respect for privacy or fear of the kind of criticism our article has generated," and suggests that "the JCN explore ways to encourage these helpful contributions, even when the patient is a family member."

An alternative suggestion is to require that any physician-author recuse himself from submitting a case report of a relative to medical journals. Let more objective physicians assess and submit this information for peer review—in an effort to eliminate conflicts of interest and, most important, to ensure the privacy and appropriate care of the patient.

* Poling also presented preliminary findings in his daughter's case in June 2001 at the Johns Hopkins Neurology Grand Rounds.

If anyone doubted the intellectual limits of Jenny McCarthy, the Weiners actress, here's unmitigated proof.

In response to Amanda Peet's characterization of antivax parents as "parasites" (which is not a far-off description), McCarthy—a supporting actress in Larry the Cable Guy's Witless Protection—tells Spectrum magazine, "I am so proud to be a parasite."

In all mustered graciousness, maybe McCarthy, featured in the straight-to-video Python, got "parasite" confused with "paragon"? Paralegal? Pair of shoes?

In any case, the same smarts that led McCarthy to accept a starring role in Dirty Love has evidently resulted in an embarrassingly limited vocabulary. Perhaps Jim Carrey will pull aside his girlfriend, who bumped boobs with Pam Anderson in Scary Movie 3, and whisper something corrective in her ear. Or maybe not. After all, he delivered that tin-ear you're-getting-on-my-nerves-like-Robin-Williams performance in Horton Hears a Who!

Peet evidently apologized for using the word "parasites" to describe antivax parents. But why is an apology necessary to someone like McCarthy, a cast member of the Untitled Patricia Heaton Project, when she views the characterization as favorable? Or maybe McCarthy (aka Yvette Denslow in BASEketball) is confused about the meaning of "proud."

Autism's False Prophets: Bad Science, Risky Medicine, and the Search for a Cure

By Paul A. Offit

328 pages

If anybody thinks Paul Offit, infectious-disease specialist at one of the nation's best pediatric hospitals, overstates the physical threats he gets from antivaccinationists, here's a sobering rebuttal: There will be no book tour for Autism's False Prophets, Offit's plain-speaking chronicle of how vaccinations have been erroneously implicated in the rise of autism. The security risk is just too high says the book's publisher, Columbia University Press.

Paul Offit has become the medical equivalent of Salman Rushdie (who went into hiding after the publication of The Satanic Verses, which prompted a fatwa from the Ayatollah Khomeini). And it's not a bad analogy, given the blind faith practiced by those who thoughtlessly adhere to and profit from, against all credible scientific evidence, the idea that vaccines are somehow responsible for a neuropsychiatric condition that is so poorly understood.

In the book's prologue, Offit—who holds a patent on a rotavirus vaccine and who vocally advocates for vaccinations in general—reveals that he gets a lot of hate mail, some of it with religious overtones. One correspondent asked, "Why did you sell your soul to the devil?" and another prays "that the love of Christ will one day flood [his] darkened heart." Offit has also received gruesome death threats ("I will hang you by your neck until you are dead!") and non-too-subtle threats toward his children. But Offit's book, most importantly, is not about Offit.

Autism's False Prophets is a systematic unpacking of the relatively short history of autism, its identification 70 years ago, its rise in frequency (which is primarily, if not exclusively, due to increased recognition), and its broad manifestations, which have driven some parents of severely affected children to the unthinkable. Other parents, desperate for treatment, have been sucked into trying one or more bogus therapies (for instance, facilitated communication), which have been hawked by one or more charlatans willing to fill the therapeutic void in allopathic medicine.

As Offit writes, some of these false prophets are credentialed; some have no medical training whatsoever. Many have been either implicitly or outrightly endorsed by the media and political figures, with no consequences for those who sow the unfounded and dangerous idea that vaccines cause autism. One of the most prominent false prophets, according to Offit, is English gastroenterologist Andrew Wakefield, who attempted to implicate the MMR vaccine as a cause of autism in the late 1990s. Wakefield's work, which received tremendous media attention, was largely funded by a personal-injury lawyer, reveals Offit, and was later discredited on charges of fraud. However, Wakefield's ideas on the dangers of the MMR vaccine contributed to England's recent measles epidemic, and astoundingly, the doctor still has his rabid supporters.

There is also the father-son duo of Mark and David Geier, who (along with others) implicate the vaccine preservative thimerosal as a cause of autism through work performed in their home-basement laboratory in Maryland. The Geiers, in particular, have migrated into shocking territory by advocating dangerous chelation therapy and chemical castration with leuprolide (Lupron; TAP) for autistic children. Offit writes how librarian and tenacious blogger Kathleen Seidel, whose child was diagnosed with a form of autism, has nearly single-handedly revealed the highly questionable nature of the Geiers' work.

Parents of autistic children, like Seidel, who refuse to neglect science or waste their time, energy, and money on unproven and far-fetched treatments, are the poorly credited heroes of the autism story. Offit reveals that he wrote Autism's False Prophets for them. However, the noise from opportunists has been cranked up by ignorant, but highly influential (and arguably financially conflicted), political figures—specifically US Congressman Dan Burton, whose grandchild was diagnosed with autism, and tort lawyer Robert F. Kennedy, Jr., a vocal proponent of the idea that thimerosal causes autism. Public figures like Burton and Kennedy have essentially ignored the series of epidemiologic studies that have exonerated vaccines as the cause of autism, mindlessly asserting that the issue should be settled in the public, instead of scientific, arena. Consequently they divert attention and funding away from credible research into the causes of autism and its treatment.

At play in this mess, Offit soundly argues, is the media's undying hunger for controversy. The idea that vaccines don't cause autism, although true and of vital public interest, isn't particularly provocative. The story's would-be title would mimic a banal headline from the parody newspaper The Onion. Moreover, science itself, which many consumers find terribly dry, isn't easily conveyed in sound bites. Case in point is the appearance of IOM president Harvey Fineberg on "Meet the Press," when he found himself contending on air (in a show of journalistic "balance") with media-savvy writer David Kirby, author of the vaccine-maligning Evidence of Harm. And if "Meet the Press" can't be counted on to provide sound information, little can be expected of Oprah.

For readers who don't believe that science is a yelling contest, the events in Autism's False Prophets—events in which self-interested figures ride roughshod all over medical evidence—will anger. Nevertheless, it is this justifiable anger that can mobilize investigations away from life-saving vaccines and onto the very elusive causes of autism.

The coverage rate in 2007 for the recommended 4:3:1:3:3:1 series* of vaccinations was 77.4%, which was comparable to rates of previous years. However, the NIS report noted "substantial variability" of coverage among states (Maryland, 91.3%; Nevada, 63.1%) and urban areas (Philadelphia, 82.2%; San Bernardino, 69.6%). Nevertheless, very few children in the examined age group (0.6%) received no vaccinations whatsoever.

Coverage rates for the 4:3:1:3:3:1 series were not significantly different among racial or ethnic groups after adjusting for poverty status, but certain vaccines (ie, 4th dose of DTaP and 4th dose of PCV7) were less likely to be received by children living at or below the poverty level, according to the report. The ethnic group composed of American Indians and Alaska Natives had the highest coverage rates for the vaccination series and specifically for MMR (96.2%), HepB (96.7%), and varicella (94.9%). 

Despite the record number of measles cases reported this year in the United States, the percentage of toddlers who received at least 1 dose of MMR vaccine has remained stable since 2004 (Table). Still nearly 8% of American toddlers did not receive vaccination for the disease in 2007, and small geographic clusters of unimmunized children appear to account for this year's record number of cases of the highly contagious disease. (For those parents who remain wary of MMR vaccination owing to unsubstantiated fears of autism, yet another study published in this week's PLoS One dispels the connection. Orac provides the necessary background and details, sparing others the trouble of posting on the subject. Hosanna.)

Data for the NIS were collected by means of telephone survey for more than 17,000 children (household response rate, 64.9%). The report acknowledges a possible underestimate of vaccine coverage owing to the exclusive use of provider-verified histories. In addition, clusters of unimmunized children were not likely to be detected, given the survey methods.

* Vaccine doses: 4 DTP/DTaP/DT, 3 polio, 1 MMR, 3 Hib, 3 Hep B, and 1 varicella.

Photo of toddler receiving pneumococcal vaccine from the CDC.

This week, the CDC's MMWR reports a total of 131 cases of the highly contagious infection in 15 US states and the District of Columbia from January 1 to July 31 (Table). The overwhelming majority of these cases were imported* (13%) or linked to imported disease (76%). (It is important to note that the number of imported measles cases in the United States has not changed appreciably over the years, but that the number of importation-associated cases accounts for this year's dubious record.) A large percentage (81%) of measles cases were related to 7 outbreaks (≥3 cases). Fifteen individuals, including 4 children younger than 15 months, were hospitalized for disease; however, there have been no deaths—yet. 

Most important, however, is the fact that a whopping 91% of cases occurred in individuals who had not received vaccination or whose vaccination status was unknown. Among these 112 patients, 85% were eligible to receive vaccination, but 66% had declined because of "philosophical or religious beliefs."