Over the past year or so, there have been several outbreaks of whooping cough (Bordetella pertussis), including one that reached epidemic levels in Washington state, which has been considered one of the worst pertussis outbreaks in the USA during the past several decades. The disease lead to 18 infant deaths from whooping cough during 2012.
The original DTP vaccine (diphtheria, tetanus and pertussis) became available in the USA in 1948 and was critical to dropping the number of cases of whooping cough from 260,000 in 1934 to less than a few thousand per year in the 1990’s. The original vaccine contained what was called “whole-cell” pertussis, which includes all of the antigens of the pertussis bacterium, partially because it wasn’t understood (and to some extent still not fully understood) which antigens on the bacteria actually induce the proper immune response to have the body destroy a pertussis infection.
Unfortunately, during the 80’s and 90’s, rare side effects of the available pertussis vaccines were noticed. Whole-cell DTP vaccines were associated with several local adverse events (for example, erythema, swelling, and pain at the injection site), fever, and other mild systemic events (for example, drowsiness, fretfulness, and anorexia), although almost all of these events are common to almost any vaccination. More severe problems were infrequently observed including convulsions, which occurred in one out of 1750 doses, and acute encephalopathy, which was extremely rare, observed in about 0-10.5 cases per million doses. Because of the safety concerns (some of which were overblown by the nascent anti-vaccination movement of the time), scientists began develop a more purified version of pertussis component called “acellular” (which constitutes the “a” portion of the vaccines used in the USA, DTaP for children and Tdap for adults). The acellular version contains fewer antigens from the pertussis bacteria, and those antigens included were assumed to be the most effective in eliciting an immune response (pdf, excellent and easy to read explanation on how vaccines cause immunity) against the disease. So in 1997, the Advisory Committee on Immunization Practices recommended the full switch from the whole-cell to acellular pertussis vaccine. Many patients were transitioned to the acellular version in 1991, and almost all children were immunized using the acellular version by 1999.
A scientific side note–this is how medical science works. They fine tune their procedures and medicines over time as more evidence becomes available. Science-based medicine adapts to new evidence, especially when weighing real risks versus real benefits (not invented ones of either). If we didn’t proceed with science based medicine, doctors would still be using bloodletting to treat diseases. Nevertheless, even with the whole-cell pertussis vaccine, the benefits far outweighed the rare risks. Acute encephalopathy is a terrible disease, if related to the whole-cell vaccine, but that risk is easily ameliorated by the 1000X higher risk of catching whooping cough and 100X higher risk of dying from that disease.
Recently, there have been several studies (1, 2 and 3 are good examples) that have discussed the effectiveness of the acellular pertussis vaccine by age, which indicated that the vaccine’s effectiveness is lower depending on how many boosters that the child received (up to 5), the age of the child, and other factors. There has been speculation in those studies that the change from the whole-cell pertussis vaccine may have resulted in a lower effectiveness of the vaccine. Even though children vaccinated with DTaP were at a much lower risk of getting the disease than an unvaccinated child (up to 25 times less likely, depending on the age).
A recent article published in Pediatrics supports the hypothesis that the whole cell vaccine is much more effective than the current acellular version. The researchers examined the medical records of Kaiser-Permanente, to determine the effectiveness of the whole-cell (wP) versus acellular (aP) vaccines. They wanted to evaluate whether disease risk in 10 to 17 year olds differed between those who previously received DTwP from those who received DTaP.
They divided the data into three groups: “Kaiser-Permante-Northern California is an integrated health care delivery system that provides care to 3.2 million members, and operates 49 medical clinics and 19 hospitals, as well as its own pharmacies and laboratories. KPNC databases capture vaccinations, laboratory tests, and inpatient, emergency department, and outpatient diagnoses.” In other words, because it is so integrated with modern computerized databases, and detailed information is available for every patient tracked by this study, the researchers could find strong evidence about what the vaccines did and didn’t do. Furthermore, another important strength of this study was complete capture of precise vaccine data, including vaccine type for every dose, for all cases and controls.We also had near complete demographic data on all subjects, so that variables such as economic status would be randomized or fully understood.. Finally, our findings were strengthened by obtaining similar results using comparisons from 2 different control groups, a pertussis negative control, and a pertussis positive control.
The researchers examined three groups: all DTwP, mixed DTwP/DTaP, and all DTaP vaccinations. Here are some of the more interesting results that they found:
- There was a correlation between increased protection against pertussis with previous receipt of whole-cell pertussis vaccines during the first 2 years of life.
- Teenagers who were vaccinated with 4 doses of DTaP vaccines were at almost 6 times higher risk of pertussis than were those who had received 4 doses of DTwP vaccines.
- Protection from pertussis appeared to be dose related, as persons who received mixed DTwP and DTaP vaccines had an intermediate level of risk between those who received all DTwP or all DTaP vaccines. In fact, those who received mixed vaccines were at nearly 4 times higher risk of pertussis than were those who received all DTwP vaccines.
- When the authors evaluated the risk of contracting pertussis with the number of acellular doses, the risk rose an average of 40% for each additional dose of acellular vaccine when compared with 4 doses of whole cell vaccine. (Note: this does not mean that the risk of contracting pertussis rose absolutely from taking the acellular vaccine, just that the risk versus the whole cell vaccine increased with each exchange of the whole cell to the acellular version).
The authors simply concluded that, “those given whole-cell pertussis vaccines in childhood were more protected than those given acellular pertussis vaccines.”
Of course, this doesn’t mean we should throw out our arms and give up. It must be made clear that those who received nothing but the acellular version of the vaccine were much better protected against whooping cough than those who had no vaccine at all. But it’s obvious, based on these and other results, that we must find a new vaccine. The authors suggested several directions to investigate:
- Bringing back whole-cell vaccines, unchanged from past versions with its known risk factors. This probably won’t happen, but if whooping cough outbreaks continue at its current pace, it might have to be considered as a stopgap measure.
- Developing a “new and improved” whole-cell vaccine. This might mean removing some antigens that might be related to the adverse effects, although it is unknown if those antigens, which cause very rare events, also give the best immune response to the vaccine.
- Related to #2, developing a “new and improved” acellular vaccine with better choices of the appropriate antigens.
- Additional doses of the acellular version. This probably is the best direction temporarily
Vaccine deniers have tended to blame the vaccine for the outbreaks and epidemic, and claim that since most kids are vaccinated during the outbreak, that either the vaccines are useless, or that it actually caused the outbreak. But the vaccine is safe, and a vaccinated child, even with the weaker acellular version, means substantially lower risk for whooping cough.
However, a more detailed analysis of the Washington state epidemic shows exactly how the infection rate breaks out between vaccinated and unvaccinated groups by age group:
- Ages 5-9 unvaccinated or under vaccinated children are 6 times more likely to become infected with pertussis than fully vaccinated.
- Ages 10-13 unvaccinated or under vaccinated are 25 times more likely to become infected with pertussis than fully vaccinated.
- Ages 14-18 unvaccinated or under vaccinated are 6 times more likely to become infected with pertussis than fully vaccinated.
In other words, when you directly compare the likelihood of catching pertussis, it’s still much safer to be fully vaccinated than not.
I cannot stress enough that science is self-correcting. It’s how it works. Observe that there seems to be an issue with the current vaccines. Hypothesize that whole cell version is better than the acellular. Test the hypothesis. Publish it. This does not mean that we are experimenting on humans with the vaccines, because we know that they are safe and effective. But with each new observation, we improve the safety and the effectiveness. We don’t do this with just vaccines, but with all medicines, all medical procedures. Heart transplants have become routine because of all of the observations made since the first, who died after 16 days (although not from failure of the transplanted heart, but because of infection). Now heart transplant patients are climbing mountains and living for 20-30 years (The Climb of My Life: Scaling Mountains with a Borrowed Heart). But don’t believe that for one minute that the person who only lived 16 days wasn’t grateful for each and everyone of those days, despite the risk.
It’s the same way for these vaccines. I much rather have years with my children because they were vaccinated, despite whatever small, immeasurably tiny risk from that vaccine.
- Klein NP, Bartlett J, Fireman B, Rowhani-Rahbar A, Baxter R. Comparative Effectiveness of Acellular Versus Whole-Cell Pertussis Vaccines in Teenagers. Pediatrics. 20 May 2013. doi: 10.1542/peds.2012-3836
- Long SS, Deforest A, Smith DG, Lazaro C, Wassilak GF. Longitudinal study of adverse reactions following diphtheria-tetanus-pertussis vaccine in infancy. Pediatrics. 1990 Mar;85(3):294-302. PubMed PMID: 2304782.
- Misegades LK, Winter K, Harriman K, Talarico J, Messonnier NE, Clark TA, Martin SW. Association of childhood pertussis with receipt of 5 doses of pertussis vaccine by time since last vaccine dose, California, 2010. JAMA. 2012 Nov 28;308(20):2126-32. doi: 10.1001/jama.2012.14939. PubMed PMID: 23188029.
- Pertussis vaccination: use of acellular pertussis vaccines among infants and young children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1997 Mar 28;46(RR-7):1-25. Erratum in: MMWR Morb Mortal Wkly Rep 1997 Aug 1;46(30):706. PubMed PMID: 9091780.
- Rohani P, Drake JM. The decline and resurgence of pertussis in the US. Epidemics. 2011 Sep;3(3-4):183-8. doi: 10.1016/j.epidem.2011.10.001. Epub 2011 Oct 14. PubMed PMID: 22094341.
- Shapiro ED. Acellular vaccines and resurgence of pertussis. JAMA. 2012 Nov 28;308(20):2149-50. doi: 10.1001/jama.2012.65031. PubMed PMID: 23188034.
- Witt MA, Katz PH, Witt DJ. Unexpectedly limited durability of immunity following acellular pertussis vaccination in preadolescents in a North American outbreak. Clin Infect Dis. 2012 Jun;54(12):1730-5. doi: 10.1093/cid/cis287. Epub 2012 Mar 15. PubMed PMID: 22423127.