Tag Archives: pertussis

Pertussis (Whooping Cough)

In another forum, I shared some very basic information on whooping cough. Recently, I was asked to post it in a place where it can be widely shared. So here it is!

Weekly Topic 02: Pertussis (Whooping Cough)

Thanks to the recent viral video of a baby with whooping cough, we’re doing pertussis this week.

In the United States, pertussis is currently the least well-controlled vaccine-preventable disease despite excellent vaccination coverage and 6 vaccine doses recommended between 2 months of age and adolescence. [E2]

What is whooping cough?

Whooping cough or “pertussis” is a coughing illness that usually lasts many weeks (“the 100-day cough”); when the child has the typical whooping cough symptoms, it’s called “classic pertussis.” Many pertussis infections are asymptomatic or present as the flu. For example, this study [1] found that among unvaccinated 10 year olds who had not had classic whooping cough, 64% had antibodies against pertussis toxin and 100% had antibodies against other pertussis antigens, indicating that 100% of unvaccinated children without history of whooping cough nevertheless had an infection but fought it off without symptoms. In this same study, they found that 61% of unvaccinated 10 year olds had had whooping cough, indicating that in a given population, about 60% will have classic pertussis and 40% will develop immunity by an asymptomatic or mild flu-like infection. Natural infection confers about 30 years of immunity [2], whereas the vaccine lasts at least one year for only 73% of recipients, and at least 2-4 years for only 34% [3]. When symptoms do appear (i.e., when the child actually gets classic pertussis), it is most severe in newborns.

Whooping cough or pertussis is caused by one of several bacteria:

  • Bordetella pertussis
  • Bordetella parapertussis
  • Bordetella holmesii

What is B. pertussis?

B. pertussis is the first bacteria we discovered that causes whooping cough. It was discovered in 1900 and is the only bacteria used for the whooping cough vaccine. Thanks to the vaccine, the bacteria has evolved and there are now two important strains to know about:

  • Pertactin-deficient or “Non-PRN” B. pertussis is a new strain that makes up 85% of B. pertussis in the U.S. today [4]. (EDIT: A later American study found 91.7% of tested B. pertussis isolates to be Non-PRN [E1]. However, this apparently varies by country and even by region within a country.) According to the CDC, those who are vaccinated are at higher risk of contracting this strain and the risk increases with more vaccine doses given [4]. EDIT: This was later confirmed by other research in humans [E2] and experiments in mice [E3].
  • PtxP3 B. pertussis is a new strain that produces more pertussis toxin and is therefore believed to be more dangerous. It was responsible for recent Australian outbreaks [5]. It is believed that the vaccinated are at higher risk of contracting this strain [6]. EDIT: This is supported by other recent research [E4]. Like Non-PRN B. pertussis, PtxP3 B. pertussis evolved in response to the vaccine. Since this strain first appeared right when whooping cough rates began increasing, it is thought to be the primary reason for the increased incidence of whooping cough [E5].
  • EDIT: The prevailing theory seems to be that the increase in pertussis rates in spite of higher-than-ever pertussis vaccination rates is due to a combination of the vaccine wearing off and vaccine resistance due to Non-PRN and PtxP3 strains [E5].

What is B. parapertussis?

B. parapertussis is another species that causes whooping cough. It was discovered in the 1930s. The vaccine may increase the risk of infection with this species 40-fold [7].

What is B. holmesii?

B. holmesii is a new species that causes whooping cough. It was discovered in 1985. The pertussis vaccine may increase the risk of B. holmesii (DTP) or have no effect on the risk of B. holmesii (DTaP) [8].

What is the popularity of these species and strains?

Knowing how common the different species and strains are can help us predict vaccine-induced risk. A study in Ohio in 2010 [9] found the proportions to be:

  • 42.3% B. pertussis (or mix)
    • estimated 36.0% Non-PRN
    • estimated 6.3% PRN+
  • 42.5% B. parapertussis
  • 15.3% B. holmesii

The only species and strain against which the vaccine protects is PRN+ B. pertussis, which makes up approximately 6.3% of all whooping cough bacteria in circulation (if we take the CDC’s report that 15% of B. pertussis is PRN+). However, the vaccine has no effect on 15.3% of all whooping cough bacteria (B. holmesii) and increases your risk of 78.5% of all whooping cough bacteria (non-PRN B. pertussis and B. parapertussis).

Look up any recent news articles about whooping cough outbreaks. Although they frequently blame the unvaccinated, if they admit how many were vaccinated, it usually disproportionately affects the vaccinated.

EDIT: In fact, the CDC itself says that the unvaccinated are not responsible for the increase in whooping cough cases over the past few decades [E9].

What about herd immunity?

Because the vaccine is so ridiculously ineffective at preventing whooping cough—in fact, it increases your risk of whooping cough, as described above—there’s no such thing as herd immunity for whooping cough. However, even if the vaccine actually prevented whooping cough, it would not contribute to herd immunity because it does not prevent a person from becoming contagious.

A 2013 FDA study [10] found that after being exposed to an animal with classic whooping cough, vaccinated baboons got infected but did not have symptoms and were contagious. In other words, vaccinated people may be protected from developing classic whooping cough caused by PRN+ B. pertussis (which was the strain used in the study and the only strain against which the vaccine protects), but they are not protected against becoming infected and contagious. In this respect, the vaccinated may pose a greater risk to vulnerable people like infants and immunocompromised individuals because they are more likely to get whooping cough caused by newer species/strains and more likely to develop a contagious asymptomatic infection caused by the vaccine-targeted strain. If they have no symptoms, they do not know they are contagious.

ETA: The lead author of the FDA baboon study also gave the New York Times an interview in which he explained that the vaccinated still develop infection when they are exposed and grow the bacteria in the backs of their throats, and thereby are contagious. He described this as “good for you, but not for the population” [E8].

What about getting the vaccine during pregnancy?

Women who get the vaccine during pregnancy develop some antibodies and pass them on to their babies–about 68.8 U/mL [E6]. However, the level of antibodies required to prevent pertussis is 246 U/mL [E7]. Not surprisingly, it has not yet been demonstrated that infants who received the Tdap vaccine during pregnancy have reduced risk of pertussis.

What’s the bottom line?

Many pertussis infections are so mild that they are not recognized as pertussis. Furthermore, the pertussis vaccine offers no real protection. It increases your risk of almost 80% of whooping cough bacteria and protects against only 6%. It also makes you susceptible to becoming a contagious asymptomatic carrier. There is no evidence that getting it during pregnancy protects your baby.

REFERENCES:

[1] http://www.ncbi.nlm.nih.gov/pubmed/8483621

[2] http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000647

[3] http://www.npr.org/sections/health-shots/2015/05/05/404407258/whooping-cough-vaccines-protection-fades-quickly

[4] see page 6: http://www.cdc.gov/maso/facm/pdfs/BSCOID/2013121112_BSCOID_Minutes.pdf

[5] http://www.ncbi.nlm.nih.gov/pubmed/22416243

[6] see slide 18: http://www.hhs.gov/nvpo/nvac/meetings/pastmeetings/2012/clark_and_messonnier_062512.pdf

[7] http://rspb.royalsocietypublishing.org/content/royprsb/early/2010/02/26/rspb.2010.0010.full.pdf

[8] http://wwwnc.cdc.gov/eid/article/18/11/11-1544_article

UPDATE 9/16/16: Looks like the above link no longer works. Here’s an archived version of the link:

http://web.archive.org/web/20160513115211/http://wwwnc.cdc.gov/eid/article/18/11/11-1544_article

[9] http://www.ncbi.nlm.nih.gov/pubmed/24445823

[10] http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm376937.htm

EDITS

[E1] http://www.nejm.org/doi/full/10.1056/NEJMc1209369#t=article

[E2] https://academic.oup.com/cid/article/60/2/223/2895696/Pertactin-Negative-Bordetella-pertussis-Strains

[E3] http://www.sciencedirect.com/science/article/pii/S0264410X14013462

[E4] http://www.sciencedirect.com/science/article/pii/S1567134812000020

[E5] http://antimicrobe.org/history/EID%20Bordetella%20pertussis%20resurgence.pdf

[E6] http://jamanetwork.com/journals/jama/fullarticle/1866102

[E7] https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jid/181/3/10.1086/315318/2/181-3-1010.pdf?Expires=1489972978&Signature=OMMSFiFaVS76957t8TD3DqtV7REjHVKLG6m7N1ZUI6ymlheDsQ~Yvg7nidXsl9u1fT8xHzndreuFmyuSuwA2Zjwp-OqYHRTIRbEmugL-Vp4osW13dp6HhG1wsHWEaTxRIgDzwALcdXbbAoi-m8fEKYL3ZwDoZBfEKwgNKRRNyTeLgoZ6ckmMSQLdVG19LGMK-SkS5203rVgTyPp6cVFsxpzjdUNcbTMiwRKYMPhs0rI-4daIYdI3TxZrjTyTzkJrZVA08drfjGpNqsfjeZBGgGaVgjUCIieRUqQ~SewbU8oxYuNCaDztquL~eKdoP~Mxsqk7M8nDOHZVPqZQxHngpA__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

[E8] http://www.nytimes.com/2013/11/26/health/study-finds-vaccinated-baboons-can-still-carry-whooping-cough.html?partner=rss&emc=rss&_r=3&

[E9] https://www.cdc.gov/pertussis/about/faqs.html

 

FOOTNOTE:

Please note that the exact proportions of species and strains differs from country to country, so the vaccine-targeted strain may make up less or more of the total in your region. The U.S. studies mentioned above should be used only as a rough estimate.

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A Brief History of Pertussis Vaccines

Previously, I wrote about the dangers of attempting to protect an infant by cocooning (vaccinating all of his adult contacts against whooping cough), demonstrating how doing so actually increases the risk to the infant rather than decreasing it. I discussed how I’ve never been a fan of influenza or HPV vaccination, but how, due to research published primarily in the last couple years, I’ve come to feel similarly about pertussis vaccination.

Whooping cough deaths and cases dropped dramatically prior to introduction of the vaccine. They continued to drop after the introduction of the vaccine, decreasing by about 99% between the mid-1940s and 1970. Vaccination rates fell in concert with rising concerns about the safety of the DTP vaccine in the 1970s-1990s. However, vaccination rates have steadily risen since then and are now at an all-time high. Nevertheless, since the 1980s, the incidence has steadily increased in spite of simultaneously increasing rates of pertussis vaccination.

As I was reading studies and articles about the many possible explanations for this paradoxical increase, I came across what was to me a fascinating and detailed (and apparently award-winning) article authored by Dr. Geier, a former researcher at the National Institutes of Health (NIH) and advisor to the Centers for Disease Control and Prevention (CDC), about the history of pertussis vaccines. After reading it, I’m amazed at how much disinformation abounds on the internet about this topic! You may not be as fascinated by the topic as am I—in which case, you can skip this one and wait for my next blog post—but I found it so interesting that I summarized the article and filled in the few blanks from a few other sources. So without further ado, I present to you a brief history of pertussis vaccination.

 

And So It Starts

In 1906, researchers Bordet and Gengou developed a technique to grow B. pertussis in a laboratory, which paved the way for the creation of a pertussis vaccine. The first whole cell pertussis (wP) vaccine was produced by Bordet and Gengou in 1912 and by 1914, there were six U.S. manufacturers of pertussis vaccines. Pertussis vaccines sans formal testing were used sporadically between 1914 and 1925. The first clinical trials of wP vaccines were published in 1925 and 1933, with the 1933 study reporting serious adverse effects for the first time in its listing of two deaths that occurred within 48 hours of vaccination. The first modern wP vaccine, which was combined with diphtheria and tetanus toxoids, was created in 1942 by Dr. Pearl Kendrick. Because the wP vaccine does not inactivate endotoxin or pertussis toxin, it may be associated with some or all the side effects of pertussis infection from fever to seizures, shock, and death. Evidence of the dangerous side effects of the wP vaccine as compared to the aP vaccine were reported as early as the 1930s and considered conclusive by the 1950s, with the first deaths reported in 1933 and the first published reports of irreversible brain damage appearing in 1947 and 1948. By 1948, there were a dozen manufacturers of DPT. The “mouse toxicity test,” which essentially determined the toxicity of the vaccine by seeing how many mice died from it, was introduced to ensure licensure of safer vaccines; however, researchers concluded in 1963 that there was no correlation between mouse safety and human safety. From the late 1940s to the early 1960s, physicians continued to use wP vaccines because they had no other choice on the market and because manufacturers hid the presence of endotoxin in the vaccine and its associated risk. Vaccine manufacturers began a successful lobbying campaign of pediatric societies and state legislators in the 1940s, ultimately resulting in legislation requiring DTP vaccination prior to school entry in most states by the mid-1960s. However, with such widespread vaccination came the first published reports of irreversible brain damage and deaths resulting from the vaccine, with these reports being published almost every year from the early 1950s through the early 2000s, with additional published reports coming out of other countries. This causal relationship was deemed definite by a report from the National Institutes of Health (NIH) in 1963. Criticism of the wP vaccine due to its high rate of adverse effects, cited at 93% in a 1984 study, increased through the 1970s and peaked in the 1980s.

 

A Better Option?

The first aP vaccine was created in the 1920s and it was obvious from at least the 1930s that it was associated with fewer adverse events than the wP vaccine. Lederle Laboratories patented a new aP vaccine in 1937, which was shown clinically to be 94% protective against disease, making it significantly more effective than the wP vaccine, and was used widely in the 1940s. However, new federal laws were passed which would require expensive and labor-intensive efficacy testing of aP vaccines, and so Lederle ceased production of its more expensive but more effective and less reactogenic aP vaccine in 1948 and began producing a wP vaccine instead. Another aP vaccine was produced in 1954 but never licensed or marketed in the U.S. due to the higher cost of production and increased clinical trial requirements. Eli Lilly Company created an aP vaccine and named it Tri-Solgen. Tri-Solgen was associated with significantly fewer adverse reactions compared to wP vaccines and was sold widely from 1962-1977, at one point capturing up to 65% of the U.S. market for pertussis vaccines. Merck Sharp & Dohme produced another aP vaccine in 1960 which was found to be both safer and more effective than the wP vaccines, but ceased production by 1963 due to the cost. The following year, 1964, Merck also removed all wP vaccines from the market citing a fear of lawsuits due to damages caused by its wP vaccine because they had a safer and more effective aP product that didn’t sell. Many other aP vaccines were produced but never marketed due to their cost and to similar concerns about legal liability due to having a safer and more effective product (the aP vaccine) but continuing to sell the more dangerous and less effective product (the wP vaccine). Due to these concerns, the market severely contracted and only four manufacturers were still producing DTP vaccines by the 1970s. Lilly ceased production of all biologic products in 1975 and sold the rights to its high quality aP vaccine Tri-Solgen to Wyeth. However, the yield was low and when Wyeth reformulated it to increase its yield, the government required new safety and efficacy trials. Wyeth determined the cost, both financial and legally, wasn’t worth it and ceased production of Tri-Solgen; specifically, Wyeth’s concerns were the same as Merck’s had been—that the studies would show the aP Tri-Solgen to be safer and more effective than Wyeth’s wP vaccine, making them legally liable for continuing to market an inferior product. Hence, the only aP vaccine on the market became unavailable after 1977. By 1984, Wyeth also completely stopped production of pertussis vaccines, again due to concerns of legal liability from its failure to produce its safer product. The end result was that only two pertussis vaccine manufacturers remained in the U.S., and both produced only the wP vaccine.

 

Trouble in Paradise

In 1975, two babies in Japan died from DPT vaccination, and these were two of 37 SIDS deaths linked to vaccination; in response, the Japanese government initially banned the DTP vaccine, but later in the year resumed vaccination in children over age 2. The following year, 1976, the government sent Dr. Sato to the NIH to study aP vaccine production. His aP vaccine was tested between 1978 and 1981 and found to be nearly 100% effective and significantly less reactogenic, and so the Japanese government mandated switching to aP vaccination in 1981. During this period, infant deaths plummeted, bringing Japan from a high 17th place in world comparison of infant mortality rates to 1st place with the lowest infant mortality rate in the world. (Coincidentally, when they reintroduced vaccinations in children as young as 3 months of age in 1988, their SIDS rate quadrupled.)

Also in the 1970s, rising awareness of vaccine adverse effects led to a reduction in the pertussis vaccine compliance rate. Pertussis is an epidemic disease–i.e., there are periodic outbreaks every 3.3 years with low disease rates in the interepidemic periods–but the interepidemic period that correlated to the lowest pertussis vaccine compliance rates was an unusually long interepidemic period with the lowest whooping cough incidence on record. In the 1970s, the U.K. determined that the benefits of continued use of wP vaccination outweighed its risks, while Sweden determined the opposite, pointing out that no one had died from pertussis since 1970 and that the causal relationship between wP vaccines and encephalopathies was too great to ignore, and banned the wP vaccine. Most studies of efficacy look only at the ability of the vaccine to produce an antibody response—termed by some “research efficacy.” However, because the presence of antibodies does not necessarily correlate to immunity, a study of actual disease rates may be used to determine the ability of the vaccine to prevent disease—termed by some “clinical efficacy.” The wP vaccines were determined to be 45-48% clinically effective while the Japanese aP vaccines when tested in Sweden were found to be 55-69% clinically effective. Even when the Swedish scientists compared a two-dose regimen of aP vaccines to a five-dose regimen of wP vaccines, the aP vaccines were found to be more effective.

In the 1970s and 1980s in the U.S., several factors contributed to consideration of abandoning wP vaccination, including: the relative absence of whooping cough in the population; improvements in medical treatment of whooping cough; the serious adverse effects of the wP vaccine, which led to health clinics requiring parents to sign an informed consent prior to receiving a wP vaccine; several SIDS deaths in 1979 which the CDC deemed to be caused by a particular lot of the wP vaccine, causing the FDA to order a recall of the defective lot, followed by a reversal of the recall and efforts by manufacturers to prevent future recalls (e.g., Wyeth began spreading lots out across the country rather than sending an entire lot to one area so that adverse effects of any one lot would not be noticed as quickly in the future); and numerous lawsuits beginning in 1981 which were ironically successful because it was argued that the manufacturers had known how to produce a safer aP product but chose not to. (Unsuccessful lawsuits had been filed previously.) In 1982, a television program about the adverse effects of DPT vaccination raised parental awareness so much that attorneys trying the cases were flooded with hundreds of requests for representation. The vaccine manufacturers attempted to stop the cases by harassing the expert witnesses, leading at least one to file a suit against them. Nevertheless, by 1985, 219 such lawsuits had been filed. Pressure from parents and especially from a group formed in 1982 called Dissatisfied Parents Together led the American Academy of Pediatrics (AAP) to conduct over 8 months of hearings to develop recommendations for the creation of a federal compensation program for vaccine-injured children. Due to the AAP’s recommendations and to the large-scale civil litigation against vaccine manufacturers, Congress introduced the National Compensation Act in 1983, which sought to limit liability for vaccine injuries. One manufacturer agreed to settle out of court for $26 million and then cite its case as an example of why the act was needed. In 1986, the U.S. Congress passed the National Vaccine Injury Act, which established, among other things, the National Vaccine Injury Compensation Program (NVICP) and essentially ended litigation against vaccine manufacturers. However, with the threat of litigation gone, manufacturers were no longer under pressure to produce a safer aP vaccine. Foreseeing that this would happen, the Congress also stipulated in the Act that the IOM hold hearings and make recommendations for improving vaccines in general and the pertussis vaccine specifically.

 

Safety Wins

As previously stated, the causal link between DPT and neurological sequelae was deemed definite by the NIH in 1963. However, after receiving several generous donations from vaccine manufacturers and being staffed and/or headed by former and current employees of vaccine manufacturers, the AAP and the Pediatric Neurology Society “mysteriously” reported in 1992 that there was no such link. This was followed by several heavily manufacturer-funded researchers publishing articles that also attempted to deny the link. Backing up a few years, we’ll examine what the government saw. In 1985, the Institute of Medicine (IOM) published a report stating, among other things, that in spite of its initially higher costs, the aP vaccine saves on overall medical costs as compared to the wP vaccine, and the United States would save millions of dollars if the wP vaccine was replaced by the aP vaccine due to the high rate of adverse reactions; it advised that the highest priority should be given to making the switch. However, this recommendation was put on the back shelf and when another IOM committee convened in 1990, only five years later, they were surprised to learn that data presented in the meeting came from their own archives. Nevertheless, the evidence against the wP vaccine was so overwhelming that, regardless of the opinions of those bought by the manufacturers, the IOM determined that the causal link between wP vaccination and encephalitis was definite. The IOM convened a third time in 1993 to again discuss the DTP vaccine and determined that it definitely causes permanent brain damage. Even the AAP failed to argue the point, instead merely notifying its members of the IOM’s position. In 1992, the FDA approved the use of aP for the boosters given at 18 months and 6 years of age. In 1996, the FDA approved the use of aP for the entire schedule. Finally, by the beginning of 2001, the wP vaccine had been removed from the U.S. market, though American manufacturers continue to produce the cheaper (in every sense of the word) wP vaccines for sale in the third world.

 

“The development and acceptance of acellular pertussis vaccine in the United States demonstrates that scientific evidence alone is not always enough to change harmful medical practices. Given the powerful resistance to change demonstrated by the pharmaceutical industry, it took years of litigation, consumer advocacy, international scientific development, and congressional action to create a new norm for childhood immunization. It would seem that open discussion of vaccine problems in the scientific and medical communities, along with policies that preclude those with a conflict of interest from determining vaccine policy, might help to prevent similar difficulties in the future in the rapidly expanding vaccination field.” (Geier & Geier, 2002, p. 284]

 

 

References

Centers for Disease Control and Prevention (1997). “Vaccination: Use of acellular pertussis vaccines among infants and young children recommendations of the Advisory Committee on Immunization Practices (ACIP).” Morbidity and Mortality Weekly Report, 46(RR-7):1-25. Retrieved from <http://www.cdc.gov/mmwr/preview/mmwrhtml/00048610.htm >.

Fine, P.E.M., & Clarkson, J.A. (1982). “The recurrence of whooping cough: Possible implications for assessment of vaccine efficacy.” The Lancet, 319(8273):666-669. doi: 10.1016/S0140-6736(82)92214-0.

Geier, D., & Geier, M. (2002). “The true story of pertussis vaccination: A sordid legacy?” Journal of the History of Medicine, 57:249-284. Retrieved from <http://www.researchgate.net/publication/11177062_The_true_story_of_pertussis_vaccination_A_sordid_legacy >.

Hieb, L. (2015). “How vaccine hysteria could spark totalitarian nightmare.” WND. Retrieved from <http://www.wnd.com/2015/02/how-vaccine-hysteria-could-spark-totalitarian-nightmare/ >.

Howson, C.P., Howe, C.J., Fineberg, H.V., eds. (1991). “B pertussis and rubella vaccines: A brief chronology.” In Adverse Effects of Pertussis and Rubella Vaccines: A Report of the Committee to Review the Adverse Consequences of Pertussis and Rubella Vaccines. Institute of Medicine Committee to Review the Adverse Consequences of Pertussis and Rubella Vaccines. Retrieved from <http://www.ncbi.nlm.nih.gov/books/NBK234365/ >.

 

Jabs for Love

DISCLAIMER: This blog post is not about pertussis vaccination overall. This blog post is about pertussis cocooning. Any rabbit trail I make is really meant to point back to the overall purpose of this blog post, which is pertussis cocooning. Did I mention this blog post is about pertussis cocooning? I now return you to your regularly scheduled program.

 

Jabs for Love

Some of my readers may be aware that I am pregnant and due to deliver in late May. I’ve recently been asked whether I want adults who plan to visit my newborn to get the whooping cough (pertussis) vaccine. This question probably arose from the CDC’s recent recommendation that adult contacts of a newborn get vaccinated so as to decrease the baby’s risk of contracting it from them [1], and from simple love—I love your unborn child and want to do everything in my power to protect him/her if I can—“jabs for love,” if you will. I generally answered privately because these days, if you express the slightest reservations over or even the strongest scientific evidence against any vaccine in any form for anybody or for any reason, you are labeled “anti-vaxx,” but I’ve been asked to share it more publicly.

Well, I would like to state that I’m not “anti-vaxx,” but I’m not sure what that label even means (nor “pro-vaxx” for that matter). And honestly, the medical profession (some of you may also be aware that I’m an ER nurse) has an equally vague term—“vaccine hesitant”—which is applied to anyone who hesitates over or questions the safety, efficacy, or necessity of any vaccine for all or for any unique individual. (For example, one of my coworkers in the ER was allergic to the flu vaccine. Because of her refusal to get one every year due to her allergy, she is technically “vaccine hesitant.”) In that case, I stand with the majority of nurses (Footnote 1) as “vaccine hesitant” due to my “hesitancy” over the influenza vaccine, which has basically been deemed worthless by a dozen Cochrane Reviews (Footnote 2). Over time, I’ve come to feel the same about the HPV vaccine, and I’ve rather recently discovered some things about the pertussis vaccine that makes me reconsider the wisdom of cocooning. And now, I’m going to put myself in mortal danger of being brutally murdered by “Big Pharma” or whoever it is “anti-vaxxers” are afraid of, by giving my answer to pertussis publicly rather than privately. Sharpen your pitchforks. 😉

 

Problems with Cocooning

I’ve seen some people suggest that the pertussis component of the adult TdaP (and pediatric DTaP) vaccine sheds, due to a misunderstanding of a certain FDA baboon study. This is not true. (The FDA news release [2] is vague and can easily be misunderstood to mean that, but if you read the study itself [3], it’s very clear, as I’ll discuss in my first point below.) If you stop to think about it, the TdaP (and DTaP) contains acellular pertussis (the aP portion), which includes only some of the components of the bacterium, not the entire bacterium. So how can you develop the growth of (be “colonized” or “infected” with) the bacteria when you’re only getting bits and pieces of it? (If someone gives you—but don’t ask me why they would—a cat’s tail and whiskers, can the cat come to life and claw you? Yes. …If you’re on LSD.) And if you can’t get an entire bacterium from the vaccine, how can you give an entire bacterium to someone else?

So I’m not afraid of the TdaP shedding and therefore won’t ask adult contacts of my newborn to avoid it for that reason. Because it just doesn’t make scientific sense.

However, although the TdaP doesn’t shed like live virus vaccines do, it:

1) Increases the risk that the recipient will become an asymptomatic carrier of B. pertussis following exposure and thereby infect others, as demonstrated in baboons in the aforementioned FDA study [2, 3] and in immunized children in an Israeli study reported by the CDC [4]. The FDA study demonstrated that following exposure to an infected baboon, baboons who had been vaccinated with acellular pertussis (as in the TdaP and DTaP vaccines) became asymptomatic carriers for 6 weeks after colonization and baboons who had been vaccinated with whole cell pertussis (as in the DTP or DTwP vaccine) became asymptomatic carriers for 3 weeks after colonization. These asymptomatic carriers then infected other baboons, demonstrating that pertussis bacteria may leap from one asymptomatic carrier to someone who is susceptible to infection by the bacteria because they were low-responders to vaccination, non-responders to vaccination, no longer immune due to waning immunity from the vaccine, or unvaccinated (Footnote 3). It’s unknown whether the bacteria can leap from one asymptomatic carrier to another asymptomatic carrier until it infects a susceptible individual.

2) May make those who do get sick with B. pertussis have milder symptoms such as no “whoop” to their cough. According to the CDC, “Adolescents and adults and children partially protected by the vaccine may become infected with B. pertussis… Pertussis infection in these persons may be asymptomatic, or present as illness ranging from a mild cough illness to classic pertussis with persistent cough (i.e., lasting more than 7 days). Inspiratory whoop is not common.” [5, p. 216] Unfortunately, this makes it harder to diagnose and more likely they’ll infect others, as in a case affecting six infants in Texas [6, para. 1] and another case affecting four newborns in Australia [7], both of which involved immunized nurses who infected newborn babies with pertussis due to a failure of physicians to diagnose their atypical symptoms.

3) Increases the risk of pertussis infection (whooping cough) caused by non-PRN strains of pertussis (pertussis bacteria lacking pertactin, a key antigen in the vaccine), as reported by the CDC. Non-PRN strains now make up over 50% of all B. pertussis isolates and a study of 752 pertussis cases in 2012 found 85% were caused by non-PRN strains. Interestingly, the vaccinated who are up-to-date on their pertussis vaccinations are more likely to become infected by these strains than the unvaccinated, reflecting a tendency for these strains to selectively attack the vaccinated. [8, pg. 6]

4) And potentially increases the risk of contracting B. parapertussis, another cause of whooping cough, 40-fold [9, 10]. I say “potentially” because this study was done in mice.

Pertussis cases have increased in spite of increasing pertussis vaccination. The FDA states, “the rates of [pertussis] infection in the U.S. have been rising over the last 30 years, despite vaccination of over 95% of children nationwide. The U.S. is now experiencing levels of pertussis comparable to those seen in the 1950s, with 48,000 cases reported in 2012.” [11, para. 3] The above four points have all been suggested as reasons for this paradoxical increase.

The FDA also states that the effects of cocooning (vaccinating all of a newborn’s adult or other contacts, which is being implemented this year in the U.S.) are unclear [11]. However, Australia, which had implemented cocooning efforts as early as 2009, abandoned it in 2012 because it was found to be ineffective at preventing pertussis infection in newborns [12].

So in summary, pertussis vaccination of adult contacts increases the risk of asymptomatic infection (increasing the risk of the infant contracting the disease); increases the risk of atypical symptomatic disease (again increasing the risk of the infant contracting the disease); increases the risk of infection and disease caused by the majority of pertussis strains (increasing the risk of the adult contact contracting the disease, therefore potentially increasing the risk of the infant contracting the disease); and potentially increases susceptibility to B. parapertussis (also increasing the risk of the adult contact contracting the disease, therefore potentially increasing the risk of the infant contracting the disease). Furthermore, cocooning has epidemiologically been found ineffective at preventing whooping cough in newborns.

So no, I won’t ask my family and friends to get vaccinated against pertussis. It just doesn’t make scientific sense.

I’m not going to tell you what to do for yourself. Getting any vaccine due to the perceived benefits to yourself, even very falsely perceived benefits as in the case of the influenza vaccine, is your choice.

However, if you want to get the vaccine solely in order to protect my child—don’t. According to the best scientific evidence from the FDA and CDC, and epidemiological evidence from Australia, you may actually be increasing my child’s risk of infection. Now, I’m not going to shriek, “Don’t visit my child if you have/haven’t gotten X vaccine, you horribleterribleawfulcrazyinsane person!!!” because I’m not ruled by fear, as are so many in these vaccine discussions. All I’m saying is that I will never ask you to protect my child by doing something that is more likely to harm him than to help him.

 

A Slight Rabbit Trail…

I think the pertussis vaccine is similar to the HiB vaccine. Once upon a time, B was the most common strain of Haemophilus influenzae (a bacterium, not a virus), accounting for over 80% of invasive H. influenzae disease in children, but now it’s significantly less common, having decreased by 99% in children (probably thanks to vaccination of children, which has also correlated to a decreased incidence of HiB in adults). Nowadays, the A and C-F strains are the most common, and the HiB vaccine offers no protection against those strains. Unfortunately, invasive H. influenzae disease, which carries a 22% fatality rate in adults, is increasing in overall incidence, probably as a result of the vaccine inadvertently shifting strain dominance from B, against which the vaccine offers protection, to strains A and C-F, against which it offers no protection [13]. In other words, the overall effect of the vaccine has been to increase all-type H. influenzae infections in spite of a 99% decrease in type B infections, including a sharp increase in the incidence of dangerous invasive H. influenzae disease. So while HiB vaccination made sense when the vaccine was first introduced, and was associated with a sharp reduction in HiB infections (a good thing!), it now has the effect of increasing overall H. influenzae infection and invasive disease rates. It would make more sense today to vaccinate against HiF (the new most common typeable strain) or against all-type H. influenzae [13], if possible, than to continue use of a vaccine that increases the overall risk rather than decreasing it.

Similarly, the introduction of the pertussis vaccine in the U.S. in the 1930s correlated to a sharp reduction in whooping cough rates (Footnote 4). However, by a process of natural selection, the vaccine has resulted in different strains not included in the vaccine gaining dominance, and, for probably manifold and complex reasons we don’t yet fully comprehend, recently increasing the overall incidence of whooping cough infections.

 

Conclusion

Like the HiB vaccine, it may be time to either update or retire the pertussis vaccine. Should the pharmaceutical companies produce an HiF or all-type Hi vaccine and update the pertussis vaccine (and I had reason to believe in their safety and efficacy, unlike the HPV and influenza vaccines), I would be far more comfortable receiving for myself or my child or recommending to potential adult contacts of my newborn those vaccines than receiving the current HiB and pertussis vaccines, which seem to rather increase the risk and incidence of infection and disease than to decrease it.

I think I can already feel the pitchforks poking. 😉

じゃあまたね!

 

Footnotes

Footnote 1: As recently as 2010, the influenza vaccination rate among healthcare providers was so low (30-50%) that the goal was only to get the rate as high as 60% by 2010 [14]. In fact, “as a group, health workers are among the most poorly covered” as regards influenza vaccination [14] and the second most common reason given by healthcare providers for getting the flu shot is “My employer requires me to be vaccinated for flu” with less than half reporting that they think it will prevent them from getting influenza [15]. Today, in an environment where influenza vaccination is often required as a condition of employment with few or no exceptions, the majority of nurses do receive the influenza vaccine at 90.5% in the 2013-2014 season [15], an increase from about 80% in the 2011-2012 season and from about 75% in the 2010-2011 season. This increase is largely attributed to employer mandates (in fact, a 2012 CDC report showed that mandatory vaccination in healthcare institutions raised compliance rates to almost 100%) rather than to a change in attitude regarding flu vaccination [16].

Footnote 2: For those who don’t know, the Cochrane Collaboration is a global, independent, nongovernmental organization that gathers, reviews, and summarizes the latest scientific knowledge from the highest quality research. Because they limit themselves to the highest quality research, and most published research today is very poor and/or biased [17], there are limits to the topics they can discuss. For example, the highest quality type of study is a double-blind, randomized, placebo-controlled trial (RCT), which means the participants are randomly assigned into one of two or more groups, at least one group gets a placebo (an ineffective treatment, such as a sugar pill or an injection of saline or water), and neither the participant nor the person administering the treatment knows whether they’re getting “the real thing” or the placebo. These randomization and double-blind placebo techniques eliminate as much as possible the chance of mind-over-matter—that is, the participant’s expectations interfering with the results—and reduces the chance of one group being lower risk than the other, which might skew the results. However, there are cases where such a study is impossible. For example, if you want to compare the safety of hospital birth to home birth, how do you randomly assign participants to hospital vs. home? Even worse, how do you make both the participant and the healthcare provider delivering the baby unaware of which “treatment” (hospital or home) is being used? Obviously, the mother is going to know whether she’s in her own house! So there are limits to what double-blind, placebo-controlled RCT’s or other high-quality research can study; therefore, by extension, there’s a limit to what the Cochrane Collaboration can review.

However, whether the influenza vaccine actually reduces the incidence of influenza infection is not impossible to study, though it may be difficult to wade through the thousands of studies on the topic to weed out the poor quality, biased ones. With that in mind, what has the Cochrane Collaboration found regarding influenza vaccination? The most recent (2014) Cochrane Review on influenza vaccination in adults reported, “The results of this review provide no evidence for the utilisation of vaccination against influenza in healthy adults as a routine public health measure.” [18]

Why is this? There are many reasons, one of which is the relatively low incidence of influenza. The CDC explains, “ILI [influenza-like illness] is a nonspecific respiratory illness characterized by fever, fatigue, cough, and other symptoms. The majority of ILI cases is not caused by influenza but by other viruses (e.g., rhinoviruses and respiratory syncytial virus [RSV], adenoviruses, and parainfluenza viruses)… [or] bacteria such as Legionella spp., Chlamydia pneumoniae, Mycoplasma pneumoniae, and Streptococcus pneumoniae.” [19, para. 2] In the same document, the CDC concludes, “many persons vaccinated against influenza will still get ILI.” [19, para. 9] In fact, about 200 viruses can cause influenza and ILI [18]. A Cochrane collaborator expounded on the CDC’s statement, explaining that during flu season, only 7% of the population suffers ILI (influenza-like illness), and of those only 11% are caused by influenza and concludes: “…evidence presented here points to influenza being a relatively rare cause of ILI and a relatively rare disease. It follows that vaccines may not be appropriate preventive interventions for either influenza or ILI.” [20, p. 3]

Another reason discussed is the high number of vaccinations that would be necessary to prevent a single case of influenza. The researchers considered the proportion of the vaccinated population that does not respond to the vaccine and subsequently gets influenza or gets a non-influenza ILI or has a vaccine reaction (which may include flu-like symptoms), any of which results in taking sick days from work, versus the proportion of the unvaccinated population that gets ILI (caused by influenza or not), which results in taking sick days from work, but obviously does not have a vaccine reaction because they were unvaccinated. Their conclusion was that so many vaccines would be required to prevent a single case of influenza and that there would be so many side effects and non-influenza ILI cases that the end result is no economic advantage (regarding the number of days lost from work versus the cost of the vaccine as regards financial cost and work days lost to illness due to or in spite of the vaccine) to vaccination. The summarized statement reads, “The preventive effect of parenteral inactivated influenza vaccine on healthy adults is small: at least 40 people would need vaccination to avoid one ILI case… and 71 people would need vaccination to prevent one case of influenza… Vaccination shows no appreciable effect on working days lost or hospitalisation…. The effectiveness of live aerosol vaccines on healthy adults is similar to inactivated vaccines: 46 people… would need immunisation to avoid one ILI case” [18].

Furthermore, statistics regarding influenza complications are likely incorrect. For example, “flu” is often billed as a major cause of pneumonia [e.g., 19; 21; 22] and the CDC lumps flu and pneumonia together in morbidity and mortality statistics [e.g., 23]. However, as reported in the British Medical Journal regarding CDC flu and pneumonia statistics, the vast majority of “flu and pneumonia” deaths involve only pneumonia (for example, 61,777 out of 62,034 or 99.59% in 2001) and of the remaining deaths attributed to flu (257 out of 62,034 or 0.41%), only 7.00% (18 out of 257 “flu” cases or 0.029% of all “flu and pneumonia” cases) were positively identified as influenza [24]. Therefore, given the relative rarity of influenza-related deaths, it should not be surprising that the 2010 Cochrane Review found “no credible evidence that there is an effect [of influenza vaccination] against complications such as pneumonia or death” [25, p. 12].

Significantly, there are also serious issues regarding bias interfering with study results. For example, a Cochrane review of influenza vaccination in children found “Extensive evidence of reporting bias of safety outcomes from trials of live attenuated influenza vaccines [which] impeded meaningful analysis” [26]. This also calls into question the validity of any claims of efficacy made by the companies producing influenza vaccines, or in studies of influenza vaccines, the majority of which are funded by the companies producing them. Furthermore, a meta-analysis or review, such as the Cochrane reviews, are only as good as the studies included in them and may be no more than a summary of the prevailing bias [17]. This makes it even more surprising that the Cochrane Review of influenza vaccination in healthy adults found no overall advantage to vaccination considering that, by their own account, about 70% of the studies included in their review had pharmaceutical industry funding and a high risk of bias, 20% had an unknown risk of bias, and only 10% had a low risk of bias [18].

The results for children are a little more complex than for healthy adults, but it appears that vaccination against influenza is completely ineffective in children under 2 years; is effective for those over age 2, with the live influenza vaccine more effective than the inactivated influenza vaccine; and is of unknown safety in any age group [26]. Interestingly, the Cochrane Review for influenza vaccination in children stated, “This review includes trials funded by industry. An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry-funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favourable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in the light of this finding.” [26] In other words, even though their review found influenza vaccination to be effective in children over age 2, they caution that the results could be largely due to bias secondary to pharmaceutical industry funding, as discussed above.

The most recent (2010) Cochrane review on influenza vaccination in older adults found that there is no evidence to recommend vaccination against influenza in older adults, either [27].

Footnote 3: “Low” or “poor” responders to vaccination, which seems to be a genetic trait and therefore not correctable by repeated vaccination, are those who develop poor or low-level antibody responses to initial vaccination and weak responses to revaccination, and lose detectable antibody levels long before the antibody response is expected to wane. For example, one study demonstrated loss of detectable antibodies against measles within 2-5 years of vaccination [28]. Low responders are estimated to make up almost 5% of the population in the case of measles vaccination [29]. I am unaware of the proportion of the population thought to be low responders specifically to pertussis vaccination. The sources I’ve found typically examine response to pertussis vaccination in newborns (not practiced in the U.S.), response to only one pertussis vaccination without boosters (not recommended in the U.S.), or response to the whole cell pertussis vaccine (not used in the U.S.).

Non-responders to vaccination refers to people who do not develop any detectable antibody response in spite of receiving the vaccine and all recommended boosters to the vaccine. Although the proportion of non-responders to each vaccine probably varies significantly, non-response occurs in 5-15% of those receiving the hepatitis B vaccine [30] and one study of pertussis vaccination in 137 infants showed similar results, with up to 91% demonstrating an immune response to full vaccination, implying a non-response rate as high as 9% following complete vaccination [31], so pertussis non-response is probably similar to hepatitis B non-response at 5-15%.

As discussed earlier, those who responded normally to vaccination but have had their immunity naturally wane over time and those who have not been vaccinated at all are also susceptible to pertussis. I don’t think it’s possible to even guess at the number of people in the population whose immunity has waned, though guesses have certainly been made. The rate of the completely unvaccinated also seems to be difficult to determine. According to the CDC, about 94.1% of children aged 19-35 months in the U.S. had received at least 3 doses of the DTaP vaccine, but this figure includes children who received only the DT without the pertussis (aP) portion, and I could not find a figure for children who have received absolutely no DTaP vaccines [32]. Therefore, knowing that most of the children reported as having received at least 3 doses of DTaP probably got at least one DTaP (i.e., a vaccine that included the pertussis portion), and that many children may have gotten one or two DTaP vaccines prior to stopping vaccination and therefore were not counted in the statistics in spite of having had some level of pertussis vaccination, 5% (and probably actually much lower) is the best guess I can come up with (understanding it is almost certainly inaccurately high) for how many children aged 19-35 months are completely unvaccinated against pertussis. It’s also definitely inaccurate to consider all completely unvaccinated children or adults to be susceptible to pertussis infection given that having had a naturally-occurring pertussis infection in the past may confer 30 or more years of natural immunity [33], meaning that the unvaccinated may not actually be in the “susceptibles” group. Then again, the same is probably true for the vaccinated who nonetheless developed natural infection. Furthermore, many people develop an appropriate antibody response to vaccination but still develop disease. So again, these are all just best guesses.

In summary, with potentially 5% of the population being non-responders to vaccination, 5-15% of the population being low-responders to vaccination, and 5% being completely unvaccinated, that adds up to about 15-25% of the population being susceptible to pertussis infection, not including those whose (vaccine-induced or naturally-induced) immunity has naturally waned or those for whom an appropriate antibody response is insufficient to confer protection. Then again, as mentioned once or twice in the DISCLAIMER at the beginning of this blog post, this post is really about the newborn’s susceptibility to pertussis related to cocooning, not the susceptibility of non-newborns.

Footnote 4: I mentioned that the introduction of the pertussis vaccine was followed by a sharp reduction in pertussis rates. While true, just so that I don’t come across as uninformed, I want to acknowledge what many anti-vaxxers point out: that the rate of pertussis was already in sharp decline long before the vaccine was introduced, and that the rate of decline did not change after the introduction of the vaccine [34]. Just so you know, yes, I am aware of that, but stating that fact in the body of the post itself would detract from my overall point. Additionally, I have no interest in discussing that topic in this post because, as discussed in the DISCLAIMER at the beginning of the post, this is about pertussis cocooning specifically, not about pertussis vaccination in general. I’ll leave you to do your own research on pertussis vaccination in general and decide whether the TdaP is superior to the Td—or, I suppose, to no vaccination—for your purposes.

 

References

  1. Centers for Disease Control and Prevention [CDC] (N.d.). “Surround babies with protection.” National Center for Immunization and Respiratory Diseases, Division of Bacterial Diseases. Last updated 27 Jan 2015. Retrieved from <http://www.cdc.gov/pertussis/pregnant/mom/protection.html >.
  2. U.S. Food and Drug Administration [FDA] (2013). “FDA study helps provide an understanding of rising rates of whooping cough and response to vaccination.” Last updated 27 Nov 2013. Retrieved from <http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm376937.htm >.
  3. Warfel, J.M., Zimmerman, L.I., & Merkel, T.J. (2013). “Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model.” Proceedings of the National Academy of Sciences, 111(2):787-792. Retrieved from <http://www.pnas.org/content/111/2/787.full.pdf >.
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  12. AAP (2012). “States ending free parent whooping vaccine.” News.com.au. Retrieved from <http://www.news.com.au/breaking-news/states-ending-free-parent-whooping-vaccine/story-e6frfku0-1226350174856 >.
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  17. Ioannidis, J.P.A. (2005). “Why most published research findings are false.” PLoS Med, 2(8):e124. doi: 10.1371/journal.pmed.0020124. Retrieved from <http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0020124 >.
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  23. CDC (2010). “Estimates of deaths associated with seasonal influenza—United States, 1976-2007.” Morbidity and Mortality Weekly Report, 59(33):1057-1062. Retrieved from <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5933a1.htm >.
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  27. Jefferson, T., Pietrantonj, C.D., Al-Ansary, L.A., Ferroni, E., THorning, S., & Thomas, R.E. (2010). “Vaccines for preventing influenza in the elderly (Version 3).” Cochrane Database of Systematic Reviews. doi: 10.1002/14651858.CD004876.pub3. Retrieved from <http://onlinelibrary.wiley.com/enhanced/doi/10.1002/14651858.CD004876.pub3 >.
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  29. LeBaron, C.W., Beeler, J., Sullivan, B.J., Forghani, B., Bi, D., Beck, C., …Gargiullo, P. (2007). “Persistence of measles antibodies after 2 doses of measles vaccine in a postelimination environment [Abstract].” Archives of Pediatrics and Adolescent Medicine, 161(3):294-301. PMID: 17339511. Retrieved from <http://www.ncbi.nlm.nih.gov/pubmed/17339511 >.
  30. Hepatitis B Foundation (N.d.). “Vaccine Non-Responders.” Last updated 21 Oct 2009. Retrieved from <http://www.hepb.org/professionals/vaccine_non-responders.htm >.
  31. Hanlon, M., Nambiar, R., Kakakios, A., McIntyre, P., Land, M., & Devine, P. (2000). “Pertussis antibody levels in infants immunized with an acellular pertussis component vaccine, measured using whole-cell pertussis ELISA.” Immunology and Cell Biology, 78:254-258. doi: 10.1046/j.1440-1711.2000.00910.x. Retrieved from <http://www.nature.com/icb/journal/v78/n3/full/icb200033a.html >.
  32. CDC (2014). “National, State, and Selected Local Area Vaccination Coverage Among Children Aged 19-35 Months – United States, 2013.” Morbidity and Mortality Weekly Report, 63(34):741-748. Retrieved from <http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6334a1.htm >.
  33. Wearing, H.J., & Rohani, P. (2009). “Estimating the duration of pertussis immunity using epidemiological signatures.” PLoS Pathog, 5(10):e1000647. doi: 10.1371/journal.ppat.1000647. Retrieved from: <http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1000647 >.
  34. Bystrianyk, R., & Humphries, S. (2013). “Vaccines: A peek beneath the hood.” International Medical Council on Vaccination. Retrieved from <http://www.vaccinationcouncil.org/2013/11/12/vaccines-a-peek-beneath-the-hood-by-roman-bystrianyk-and-suzanne-humphries-md/ >.

 

EDITS

16 July 2015: Noticed that all the links in the references were broken. Fixed all the links. Noticed that one link was missing (reference #32). Added link.