Study: Whooping cough resurgence due to vaccinated people not knowing they’re infectious?

Public Release: 24-Jun-2015

Santa Fe Institute

Credit: Courtesy of B. Althouse and S. Scarpino

Whooping cough has made an astonishing comeback, with 2012 seeing nearly 50,000 infections in the U.S. (the most since 1955), and a death rate in infants three times that of the rest of the population. The dramatic resurgence has puzzled public health officials, who have pointed to the waning effectiveness of the current vaccine and growing anti-vaccine sentiment as the most likely culprits.

But that might not be the whole story, suggests a new study published in BMC Medicine by Santa Fe Institute Omidyar Fellows Ben Althouse and Sam Scarpino. Their research points to a different, but related, source of the outbreak — vaccinated people who are infectious but who do not display the symptoms of whooping cough, suggesting that the number of people transmitting without symptoms may be many times greater than those transmitting with symptoms.

In the 1950s, highly successful vaccines based on inactivated pertussis cells (the bacteria that causes whooping cough) drove infection rates in the U.S. below one case per 100,000 people. But adverse side effects of those vaccines led to the development and introduction in the 1990s of acellular pertussis vaccines, which use just a handful of the bacteria’s proteins and bypass most of the side effects. (Currently given to children as part of the Tdap vaccine.)

The problem is, the newer vaccines might not block transmission. A January 2014 study in PNAS by another research team demonstrated that giving baboons acellular pertussis vaccines prevented them from developing symptoms of whooping cough but failed to stop transmission.

Building on that result, Althouse and Scarpino used whopping cough case counts from the CDC, genomic data on the pertussis bacteria, and a detailed epidemiological model of whooping cough transmission to conclude that acellular vaccines may well have contributed to — even exacerbated — the recent pertussis outbreak by allowing infected individuals without symptoms to unknowingly spread pertussis multiple times in their lifetimes.

‘There could be millions of people out there with just a minor cough or no cough spreading this potentially fatal disease without knowing it,’ said Althouse. ‘The public health community should act now to better assess the true burden of pertussis infection.’

What’s worse, their model shows that if the disease can be spread through vaccinated, asymptomatic individuals essentially undetected, the level of vaccination needed to protect those that are unvaccinated (so-called ‘herd immunity’) is over 99 percent, impractically high at a time when anti-vaccine campaigns are turning people away from vaccination.

Their results also suggest that a practice called cocooning, where mothers, fathers, and siblings are vaccinated to protect newborns, isn’t effective. ‘It just doesn’t work, because even if you get the acellular vaccine you can still become infected and can still transmit. So that baby is not protected,’ Althouse says.

Does this mean the current vaccine is useless? Not at all, the pair says. Until researchers can develop a new pertussis vaccine that blocks transmission, the protection the acellular vaccine offers to individuals is vital.

‘It’s the symptoms of pertussis infection that kill people,’ Scarpino says, ‘and the existing vaccine prevents the most debilitating effects of whooping cough.’

In that sense, the research underscores the importance of getting vaccinated, especially for children. ‘There are lots of people out there who may be transmitting pertussis unknowingly,’ Scarpino says. ‘Not vaccinating your own child puts her or him at increased risk of severe disease, even death.’

Journal Reference:

  1. Benjamin M. Althouse, Samuel V. Scarpino. Asymptomatic transmission and the resurgence of Bordetella pertussis. BMC Medicine, 2015; 13 (1) DOI: 10.1186/s12916-015-0382-8

Whooping Cough Vaccine is obsolete ” Bulk of the cases were in fully vaccinated children ” few cases among unvaccinated children

Why Whooping Cough Vaccines Are Wearing Off

Doctors race to protect kids as whooping cough vaccines wear off

By Maryn McKenna  | Tuesday, October 1, 2013

By late summer 2010 an alarming number of children in California had developed pertussis, or whooping cough—five times as many as in the first half of 2009. David Witt, a physician and infectious disease specialist who works at Kaiser Permanente San Rafael Medical Center, cared for some of those sick children. His practice lies in the heart of Marin County, the famously counterculture spit of land north of San Francisco. At first, he assumed that the outbreak was a consequence of parents refusing vaccinations for their children. As the incidence continued to climb month after month, however—not just in northern California but all across the state—Witt began to wonder whether something else was going on.

Working with his college-age son Maxwell and his pediatrician colleague Paul Katz, Witt retrieved the records for 132 Kaiser Permanente patients younger than 18 who had tested positive for pertussis between March and October 2010.

“The bulk of the cases were in fully vaccinated children between eight and 12 years old,” Witt says. “That was a total surprise.”

As Witt’s small study spotted, and larger ones have since confirmed, protection granted by the vaccine, which has been used for the past two decades, is wearing off much faster than public health planners anticipated. Rates of pertussis increased at least threefold between 2011 and 2012 in 21 states. Whereas some of these cases occurred among children who had never been vaccinated, most of the affected children had in fact received vaccines; those inoculations simply failed to safeguard them over the long term.

Now health authorities are scrambling to devise new strategies for protecting kids. There are no easy solutions. No one is developing a better vaccine to replace the current one. Attempting to recommend additional shots would trigger years of public health debate, and it is not clear whether extra doses of vaccine would make a difference. Even discussing the problem provokes uneasiness: with antivaccine sentiments and vaccine refusal at historic highs, nobody wants to impeach one of public health’s crucial tools.

Adverse Reactions Before a vaccine became available in the 1940s, many parents learned firsthand that pertussis was a terrible disease. The bacterium that causes it, Bordetella pertussis, produces a toxin that damages the tiny sweeping hairs that coat the lining of the lungs, preventing them from clearing the airways of mucus and the microbial invaders. Following uncontrollable coughing fits—some of which are strong enough to cause seizures and brain damage—children wheeze and gasp for breath, giving the illness its name. In the pre-vaccine era, whooping cough afflicted as many as 200,000 children each year in the U.S. and killed about 8,000. The new vaccine shrank the incidence of pertussis from around 157 cases for every 100,000 members of the population to one in 100,000.

This success came at a cost, though. Researchers crafted the original pertussis vaccine from dead pertussis bacteria that could not reproduce but retained many microbial proteins by which immune cells could recognize and attack B. pertussis before it caused disease. Unfortunately, those whole-cell preparations also contained other molecular components that could cause unwanted immune system reactions, such as swelling near the injection site and, in rare cases, high fevers that could dangerously inflame the brain. “People didn’t pay much attention to the reactions in the early days, because the death rate before the vaccine came along had been so staggering,” says James Cherry, a longtime professor of pediatrics and vaccine researcher at the David Geffen School of Medicine at U.C.L.A.

Over the next few decades, however, concern surrounding the vaccine’s side effects intensified. In the 1970s Sweden and Japan ceased using the vaccine altogether. A government study published in England in 1981 concluded that the vaccine caused permanent brain damage once in every 310,000 doses (a result that was later disputed). And in 1982 an NBC broadcast aired criticisms of the vaccine, turning public opinion against it and jump-starting the U.S. antivaccine movement.

The U.S. and other countries began industry-wide efforts to find a better vaccine, focusing on “acellular” formulas that used a few purified bacterial proteins to establish immunity rather than the whole cell, reducing the risk of inflammatory reactions. Researchers combined the new pertussis vaccine with vaccines against tetanus and diphtheria. DTaP, as it was known, was ready for the doctor’s office in 1992. In the U.S., children receive it at two, four and six months; once between 15 and 18 months; and once between the ages of four and six, before they enter school.

From the start, public health authorities understood that an acellular vaccine might confer more temporary immunity than the problematic whole-cell vaccine. So, in 2005, they added a booster to the regimen to guarantee that children would be protected throughout adolescence. Officials determined the booster would be most effective for 11- to 12-year-olds but authorized it for use in any adult, eventually including pregnant women.

A Failure to Protect After California’s 2010 pertussis outbreak, additional outbreaks hit Wisconsin, Vermont and Washington, among other states, in 2012. Analyses of who was getting sick revealed the same pattern every time. Tom Clark, a physician and pertussis expert at the Centers for Disease Control and Prevention, describes it as a “striking stair-step appearance, rising by year: six, seven, eight, nine, 10 years old. If you go back several years [to when whole-cell vaccines were used], that stair-step is not there.”

The stair-step indicated that the more time elapsed since a child’s most recent pertussis shot, the more likely the child would develop whooping cough after exposure to the bacteria. Many of these children were too young to have received their booster, so researchers hoped that once children got their additional shots, the unpredicted vulnerability would cease. New data from the Washington State outbreak quashed that hope: 13- and 14-year-olds were catching pertussis even after they received their booster shot. Other studies demonstrated that the vaccine was behaving differently from the older, reactive one: children who had received even one dose of the older, whole-cell formula while it was still on the market were better protected against pertussis than those who received only the newer vaccine. (Of course, children who received the new vaccine were still better off than those who had never been vaccinated.)

Clark points out that the original research on acellular vaccine in the 1980s tested whether it would protect but not for how long it would protect. Some diseases for which acellular vaccines are typically used, such as Hib meningitis, are only dangerous to children for a short time early in life, so long-lasting immunity is not necessary. Today, however, immunologists have better laboratory tools and a much more nuanced understanding of how immunity is evoked and sustained. “A lot of what you would do to develop a vaccine today was never done for the pertussis vaccine,” Clark says.

“The big answer is that we need a better vaccine,” says Mark Sawyer, a professor of clinical pediatrics at the University of California, San Diego, and chair of a working group collaborating with the Advisory Committee on Immunization Practices (ACIP), which helps to set federal vaccine policy. “But the ACIP can’t just make that happen. That is up to the scientists who would do a study of what would make a better vaccine, and it is up to the pharmaceutical companies.”

If a new vaccine were formulated, demonstrating its superiority would be challenging. Every developed country vaccinates its children against pertussis, so there is no large unprotected population that could help prove a new vaccine’s worth. And before encouraging manufacturers to consider developing a new vaccine, federal planners would have to weigh the unintended consequences of the endeavor. Diverting too much of the manufacturers’ limited resources to one new vaccine could cause shortages of others, for example. Another concern is whether parents would heed the advice to bring children in for yet more shots.

The ACIP has been researching the problem for more than a year. The committee is in uncharted territory because this type of failure has never occurred with any other vaccine. In June the working group concluded that because the booster’s protection against pertussis is so short-lived, adding more shots to the typical regimen would do little to reduce the overall prevalence of pertussis. The group therefore advised the committee not to change policy to include a second booster in adulthood but rather to increase the number of pregnant women who get their booster in the first place. The CDC estimates that currently only 6 percent of pregnant women receive the shot. Yet newborns, who cannot be vaccinated, are the most vulnerable to the dangerous effects of pertussis; improving the immunity of their closest contacts could be the best way to prevent pertussis deaths.

Given the current vaccine’s faults, Clark says bluntly that in the general population “there’s going to be a lot of pertussis.” But he adds that although pertussis cases are increasing, deaths are not; when vaccinated children develop whooping cough, they have milder symptoms. So the newer pertussis vaccines are still valuable because they reduce not just the likelihood of death and severe illness but also the health care spending—not to mention emotional trauma—that accompany those dire results. On that basis, Sawyer says, public health officials should urge the 90 percent of American teens and adults who failed to get their booster shot to receive one and thereby protect both themselves and the most vulnerable among us. “We do need a new vaccine,” he says. “But we can do a lot better with the ones we have.”

http://www.scientificamerican.com/article.cfm?id=why-whooping-cough-vaccines-are-wearing-off

Individuals had a 40 percent increased risk of pertussis for each additional acellular dose received (as compared to receipt of a DTwP dose) between ages 1-24 months

Contact: Vincent Staupe vstaupe@golinharris.com 415-318-4386 Kaiser Permanente

Whole-cell vaccine was more effective than acellular vaccine during California pertussis outbreak

OAKLAND, Calif., May 20, 2013 — Whole-cell pertussis vaccines were more effective at protecting against pertussis than acellular pertussis vaccines during a large recent outbreak, according to a new Kaiser Permanente study published in Pediatrics.

Whole-cell pertussis vaccines, also called DTwP, were available from the 1940s to 1990s, but were associated with safety concerns that ultimately led to the development of acellular pertussis vaccines, which are also called DTaP. By the late 1990s, the United States had switched from whole-cell to acellular vaccines for all five recommended infant and childhood doses.

The study, which followed the 2010-2011 pertussis outbreak in California, examined 10- to 17-year-olds who received the recommended four pertussis-containing vaccines. The researchers evaluated the risk of pertussis during the outbreak according to the number of whole-cell and/or acellular pertussis vaccines these participants had received as infants and toddlers.

Despite high levels of vaccine coverage, pertussis epidemics have arisen every three to five years since the 1980s, with progressively higher incidence rates over time. “Studies have suggested that protection following the acellular pertussis vaccine is less enduring than following the whole-cell pertussis vaccine,” said lead author Nicola Klein, MD, PhD, co-director of the Kaiser Permanente Vaccine Study Center and a pediatrician. “Although reasons for the recurrent pertussis outbreaks are complex, waning protection following five doses of acellular pertussis vaccine plays a central role, at least in recent epidemics.”

The study included 138 individuals with confirmed pertussis, 899 individuals who had a lab test indicating they did not have pertussis, and 54,339 individuals who were similar to those with confirmed pertussis on sex, race/ethnicity, medical clinic, and membership status.

Increased number of acellular doses from zero to four was significantly associated with an increasing percent of positive pertussis tests. On average, individuals had a 40 percent increased risk of pertussis for each additional acellular dose received (as compared to receipt of a DTwP dose) between ages 1-24 months.

Teenagers who were vaccinated with four doses of acellular vaccines were at almost six times higher risk of pertussis than were those who had received four doses of whole-cell vaccines. Persons who received mixed whole-cell and acellular vaccines had an intermediate level of risk between those who received all whole-cell or all acellular vaccines. Those who received mixed vaccines were at nearly four times higher risk of pertussis than were those who received all whole-cell vaccines.

Earlier studies by Kaiser Permanente have shown that protection from the fifth dose of acellular pertussis vaccine wanes substantially during the five years after vaccination among children 4 to 12 years of age who have only received the acellular vaccine. The current study included only individuals born in 1999 or earlier, for whom at least five years had passed since receipt of the fifth pertussis vaccine.

Since 2005, the Advisory Committee on Immunization Practices has recommended boosting with reduced antigen content acellular pertussis vaccine, also known as Tdap, for persons 11 years and older. The study found that a booster dose of Tdap did not overcome the advantage in protection from pertussis seen among those who had received four doses of the whole-cell vaccine.

“The results indicate that a booster dose of Tdap does not overcome the advantage in protection from pertussis afforded to those who previously received four doses of the whole-cell vaccine,” Dr. Klein said. “Despite this, boosting the newly emerging cohort of acellular pertussis vaccine-only teenagers with Tdap remains the best means currently available to help protect this group against disease.”

Studies demonstrate that whole-cell and acellular pertussis vaccines administered to infants trigger different immune responses that at least partially persist through the teenage years, but long-term clinical consequences of such differences have been unknown. The results of this study, the researchers said, suggest that variations in immune responses induced by primary immunization during infancy play a central role in protection from disease years later. Additionally, the study highlights the need for new pertussis vaccines that provide both an improved safety profile and long lasting immunity.

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Additional authors on the study include Joan Bartlett, MPH, MPP; Bruce Fireman, MA; Ali Rowhani-Rahbar, MD, MPH, PhD; and Roger Baxter, MD, of  Kaiser Permanente Division of Research in Northern California.

This research was supported by funding from Kaiser Permanente.

About the Kaiser Permanente Division of Research

The Kaiser Permanente Division of Research conducts, publishes and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and the society at large. It seeks to understand the determinants of illness and well-being and to improve the quality and cost-effectiveness of health care. Currently, DOR’s 600-plus staff is working on more than 250 epidemiological and health services research projects. For more information, visit http://www.dor.kaiser.org.

About Kaiser Permanente

Kaiser Permanente is committed to helping shape the future of health care. We are recognized as one of America’s leading health care providers and not-for-profit health plans. Founded in 1945, our mission is to provide high-quality, affordable health care services and to improve the health of our members and the communities we serve. We currently serve more than 9.1 million members in nine states and the District of Columbia. Care for members and patients is focused on their total health and guided by their personal physicians, specialists and team of caregivers. Our expert and caring medical teams are empowered and supported by industry-leading technology advances and tools for health promotion, disease prevention, state-of-the-art care delivery and world-class chronic disease management. Kaiser Permanente is dedicated to care innovations, clinical research, health education and the support of community health. For more information, go to: kp.org/newscenter.

Protection from Pertussis Vaccine, after the fifth dose wanes more than 40 percent each year

Protection Against Whooping Cough Waned During the Five Years After Fifth Dose of DTaP

ScienceDaily (Sep. 12, 2012) — Protection against whooping cough (also called pertussis) waned during the five years after the fifth dose of the combined diphtheria, tetanus, acellular pertussis (DTaP) vaccine, according to researchers from the Kaiser Permanente Vaccine Study Center. The fifth dose of DTaP is routinely given to 4- to 6-year-old children prior to starting kindergarten.

The study appears in the current online issue of the New England Journal of Medicine.

This is the first study to specifically focus on the large population of highly vaccinated children who had exclusively received DTaP vaccines since birth and for whom enough time had passed since their fifth dose that DTaP vaccine waning could be measured, said the researchers. They explained that the study period included a large pertussis outbreak that occurred in California during 2010. Researchers examined the relationship between time since vaccination with the likelihood of a positive pertussis test in the Kaiser Permanente Northern California population, which includes 3.3 million members in an integrated care system with electronic medical records and a central laboratory.

Researchers compared 277 children, 4 to 12 years of age, who were positive for pertussis with 3,318 children who were negative for pertussis and separately with 6,086 matched controls. They assessed the risk of pertussis in children from 2006 to 2011 in California relative to the time since the fifth dose of DTaP and found that protection from pertussis after the fifth dose of DTaP vaccine wanes more than 40 percent each year. The amount of protection remaining after five years depends heavily on the initial effectiveness of the fifth dose of DTaP, according to Nicola Klein, MD, PhD, co-director of the Kaiser Permanente Vaccine Study Center and the lead author of the study.

If the initial effectiveness of the fifth dose of DTaP was 95 percent, the effectiveness of DTaP would decrease to 71 percent after five years. Whereas if the initial effectiveness was 90 percent, it would decline to 42 percent after five years, explained the researchers.

“The findings suggest that whooping cough control measures may need to be reconsidered. Prevention of future outbreaks may be best achieved by developing new pertussis-containing vaccines or reformulating current vaccines to provide long-lasting immunity,” said Klein.

“That said, the DTaP vaccine is effective and remains an important tool for protection against whooping cough for children and the communities in which they live, and following current CDC recommendations remains important.”

The CDC currently recommends five DTaP shots for children. The first three shots are given at 2, 4, and 6 months of age. The fourth shot is given at 15 through 18 months of age, and a fifth shot is given when a child enters school, at 4 through 6 years of age.

The first pertussis vaccine was developed in the 1930s and was in widespread use by the mid-1940s, when pertussis vaccine was combined with diphtheria and tetanus toxoids to make the combination whole cell pertussis vaccine DTP. In 1991, concerns about DTP safety led to the development of the acellular pertussis DTaP vaccines that are associated with fewer side effects. DTaP vaccines have completely replaced the whole cell DTP vaccines in the United States as well as in many countries around the world.

Why Do Pertussis Vaccines Fail? It Suggest Corrupted Science

Original Abstract:
Why Do Pertussis Vaccines Fail?
James D. Cherry, MD, MSc
Pediatric Infectious Diseases, Mattel Children’s Hospital University of California Los Angeles, and the Department of Pediatrics, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California
KEY WORDSpertussis
DTP
DTaP
adolescent- and adult-formulated tetanus and diphtheria toxoids and acellular pertussis vaccine
•Abbreviations: DTaP — pediatric diphtheria and tetanus toxoids and acellular pertussis vaccineDTP — pediatric diphtheria and tetanus toxoids and whole-cell pertussis vaccineFHA — filamentous hemagglutininFIM — fimbriaePCR — polymerase chain reactionPRN — pertactinPT — pertussis toxinWHO — World Health Organization

Possible Reasons Why DTP, DTaP, and Adolescent- and Adult-Formulated Tetanus and Diphtheria Toxoids and Acellular Pertussis Vaccines Fail

The first reason, and perhaps the most important one, is that our estimates of vaccine efficacy have been inflated because of case definition.3–11 At the time of the pediatric diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine efficacy trials in the early 1990s, it was hoped that a universal case definition could be developed so that the results of the various trials could be compared. To this end, the World Health Organization (WHO) case definition was developed.3 The primary case definition required laboratory confirmation and ≥21 days of paroxysmal cough. I was a member of the WHO committee and disagreed with the primary case definition because it was clear at that time that this definition would eliminate a substantial number of cases and therefore inflate reported efficacy values.4–11 Nevertheless, the Center for Biologics Evaluation and Research of the Food and Drug Administration accepted this definition, and package inserts of the US-licensed DTaP vaccines reflect this. For example, Infanrix (containing 25 μg pertussis toxin [PT], 25 μg filamentous hemagglutinin [FHA], and 8 μg pertactin [PRN]) and Daptacel (containing 10 μg PT, 5 μg FHA, 5 μg fimbriae [FIM]-2/3, and 3 μg