There are a number of factors that contributed to the recent pertussis
outbreak in California, including waning immunity to diphtheria and tetanus
toxoids and acellular pertussis vaccines and a lack of vaccination among
certain populations, according to the latest data presented at recent meetings.
Results of several studies presented during the 49th Annual Meeting of
the Infectious Diseases Society of America in Boston indicated that the
effectiveness of acellular pertussis vaccines wanes substantially over time,
but that the tetanus-diphtheria-pertussis vaccines, which are recommended for
adolescents, are helpful in boosting protection rates overall. That is the hope
of the Advisory Committee on Immunization Practices, which recently recommended
Tdap for pregnant women, besides adolescents.
Sarah S. Long, MD, from St.
Christopher’s Hospital for Children, said a booster dose of Tdap is
recommended at ages 11 to 12 years.
Photo by St. Christopher’s Hospital for
“With California having recently experienced the worst whooping
cough outbreak in 60 years, it is all of our hopes that women will take
advantage of this opportunity in the same manner by which they do other things
for the benefit of their babies,” David W. Kimberlin, MD, who is an
Infectious Diseases in Children Editorial Board member and an AAP
committee representative at the ACIP, said in an interview.
According to the CDC, 27,550 cases of pertussis were reported in the
United States in 2010, with about 10,000 of those occurring in California.
Although the outbreak in California has diminished substantially — as of
September, health officials reported about 2,500 cases of pertussis in the
state in 2011.
“These numbers are still much higher than we’d like to
see,” said Kathryn M. Edwards, MD, who is also an Infectious
Diseases in Children Editorial Board member. And that, Edwards said, is the
reason many health experts are working to determine the reasons why this
outbreak has occurred, and what can be done to stop it. Edwards is the chair in
pediatrics at Vanderbilt University, Nashville, Tenn.
Origins of outbreak
Results of several studies presented at the annual IDSA meeting
indicated that use of acellular pertussis vaccines likely played a key role in
the California outbreak.
A late-breaker presentation by Kaiser Permanente researcher Roger P.
Baxter, MD, and colleagues concluded that “acellular vaccines appeared
to provide less protection than the whole-cell vaccines they replaced, and
their effectiveness may wane substantially over time.”
Roger P. Baxter, MD
“The efficacy of the fifth dose of DTaP wanes by more than 40% per
year,” Baxter told Infectious Diseases in Children.
Irini Daskalaki, MD, of the Philadelphia Department of Public
Health, presented data that backed those findings. In this paper, which looked
retrospectively at 43 children reported to a city immunization registry, the
researchers concluded: “Even in a very limited window of risk (5 years),
children who received their last childhood DTaP vaccination at an earlier age
tended to be at increased risk for pertussis. This increased risk for pertussis
in 7- to 11-year-old children is likely due to waning immunity, which could be
minimized through administration of DTaP closer to 6 years of age rather than
at 4 years of age.”
Sara Tartof, PhD, MPH, an epidemiologist with the CDC, reached
similar conclusions in her presentation at IDSA: “Incidence rates of
pertussis increase in magnitude over the 5 years following completion of the
five-dose DTaP series, suggesting waning immunity 3 to 5 years after the
completion of the DTaP series.”
In related study data also presented at IDSA, CDC researchers calculated
that vaccine effectiveness estimates “across all ages for five DTaP doses
compared with zero doses was 85.9% (95% CI, 75.6-91.9). The recommended
childhood vaccination schedule for pertussis permits a four-dose schedule if
the fourth dose is received after a child’s 4th birthday. The preliminary
[vaccine effectiveness] estimate across all ages for the four-dose schedule
compared with zero doses was 80.4% (95% CI, 62.5-89.8).”
For the five doses, the preliminary vaccine effectiveness estimate
compared with zero doses decreased from 94.7% in children aged 4 to 5 years to
84.9% in children aged 6 to 7 years, and to 81.1% in children aged 8 to 10
These findings led the CDC researchers on that paper to conclude:
“Although overall vaccine efficacy is good, the relative drop of 14% from
the 4- to 5-year-olds to the 8- to 10-year-olds suggests that waning of
immunity is occurring.”
In an interview with Infectious Diseases in Children, Tartof said
her study looked at data on children born between 1998 and 2003 who had five
doses of DTaP recorded in the Minnesota Immunization Information Connection,
with the fifth dose received between the ages of 4 and 6 years. The researchers
used statewide pertussis surveillance data between 2004 and 2010 to identify
those children within the cohort who developed pertussis anyway, and “in
the 5 years of follow-up beginning at the time of receipt of their fifth DTaP
dose, 358 cases of pertussis developed in this cohort. The incidence rates of
pertussis in these 1 to 5 years of follow-up were 22.5 (16.7-29.9); 29.1
(22.3-37.3); 42.4 (33.8-52.4); 54.4 (43.5-67.2); and 78.2 (63.2-95.7)
respectively. Analyses to calculate adjusted relative rates are ongoing.”
Tartof said her data, taken together with other data presented at IDSA,
suggest that “we are seeing a shift in the epidemiology of pertussis to
the 7- to 10-year-olds, which is different than what we saw in 2005, which was
more pertussis in the 11- to 12-year-olds.”
In a talk about the shifting epidemiology of pertussis during the IDSA
meeting, Stanley A. Plotkin, MD, said pertussis is an important public
health problem in Japan and Switzerland, as well, despite sustaining high
vaccination rates. The evidence that acellular vaccines give less lasting
immunity than whole-cell vaccines is accumulating in many countries throughout
the world, and it is necessary to evaluate whether improved acellular pertussis
vaccines are needed for better control of pertussis, Plotkin said.
Stanley A. Plotkin, MD
“Age distribution of pertussis seems to have shifted toward older
children, adolescents and adults in countries with high vaccine coverage,”
said Plotkin, emeritus professor of the University of Pennsylvania and adjunct
professor at Johns Hopkins University. “Decreased transmission in
childhood is leading to a lower force of infection, less natural boosting due
to subclinical infections and to more susceptible older people.”
But, even with waning immunity, Baxter said vaccination makes a
difference. Data in his study suggest that “those children who were not
up-to-date were twice as likely to have pertussis as those children who were
The researchers said the pattern of pertussis incidence by age
“closely paralleled the age-related pattern of acellular vaccine use
during infancy.” Baxter, who is co-director of the Kaiser Permanente
Vaccine Study Center, said this data suggests that more education is needed on
Strategies for intervention
Baxter and colleagues also said Tdap vaccination was 55% effective
against pertussis (95% CI, 37-61). ACIP members said they are hoping that this
booster effect will have a positive result on overall pertussis rates, as they
recently recommended TDaP for all pregnant women and have built that
recommendation into the 2012 adult immunization schedule.
Sarah S. Long, MD, who is chief of infectious diseases at St.
Christopher’s Hospital for Children in Philadelphia, said the changes
recommend that all pregnant women who have been pregnant for more than 20 weeks
should receive Tdap.
Long said these recommendations follow data by the CDC indicating that
more than 80% of expectant mothers are willing to get the vaccine, and that a
“cocooning strategy,” which was recommended by the CDC in 2006, did
not sway vaccination rates in family members of new infants.
“This strategy has been completely unsuccessful,” Long said
during a recent presentation at the AAP National Conference and Exhibition held
Edwards said this cocooning strategy is difficult to enforce:
“Cocooning is hard to do. Dr. Carol Baker [who is head of the department
of pediatric infectious diseases at Baylor College of Medicine, Houston and
also sits on the ACIP] has data that show that the cocoon strategy didn’t
work for one hospital, and that it was often just a function of some people
being missed for vaccination during that postpartum period. Even missing one
can lead to failures with this strategy.”
Long said many pregnant women are receiving the tetanus and diphtheria
vaccine while pregnant already, and adding the pertussis component is expected
to provide at least some antibodies to neonates.
She also said this change in strategy is important because most
pertussis-related morbidity and mortality in children occur in those babies
aged younger than 4 months, or those children who are too young to be protected
by DTaP vaccination.
There may be some issues once pregnancy Tdap recommendations are put
into place, including a possible blunting of immune response to the
babies’ first DTaP vaccination in the first 2 to 6 months of life, since
this has already been demonstrated in some studies, according to Long. However,
the data seem to indicate that although blunted responses occur initially to
those babies who are exposed to Tdap in utero, their antibodies seem to catch
up to those infants who were not exposed in utero by 15 to 18 months of age.
The early blunting is not likely to be a major cause of concern, Long
said, because it does not matter where the infant’s antibody comes from as
long as the infant has some. And this strategy is likely to protect very young
infants from death.
According to Long, “changes in the recommendations for pertussis
vaccine are needed because disease incidence in infants is rising and disease
Targeting pregnant women for vaccination is a good strategy because
other data have shown that giving pertussis vaccines at birth leads to
interference with other vaccines, specifically Haemophilus influenzae
type b, Long said.
That is why the primary series currently includes four doses given at
ages 2, 4, 6 and 15 to 18 months. A fifth (booster) dose is recommended when
the child is aged 4 to 6 years. Also, a booster doses of Tdap are recommended
at ages 11 to 12 years.
Continue to immunize
Howard Backer, MD, MPH, who is director of the California
Department of Public Health, said the best way for pediatricians to assist in
halting the outbreak is to encourage parents to ensure their adolescent’s
immunizations are up-to-date in compliance with a new California law that went
into effect earlier this year. The law, AB 354, requires documentation of an
adolescent pertussis booster shot before school entry. More than 1 million
students statewide remained unvaccinated before the fall semester.
“Vaccination, including critical booster shots, is the best defense
against pertussis,” Backer said. “Parents of seventh- to 12th-graders
must ensure that their children receive the necessary booster shot to avoid a
delay in having their children start school.”
Tartof said more data are probably needed before a policy shift is made
to adding another dose of Tdap in the 7- to 10-year-old groups.
“There are a number of considerations before recommending a change
in vaccination policy, including cost, and what is driving this waning
immunity. Is it the manufacturer, the components of the vaccine, and all of
this needs to be studied,” she said, adding that she hopes to expand her
data beyond her cohort to other states.
“If women are not vaccinated by the time their babies are born,
they still need to get vaccinated postpartum because using that cocoon strategy
makes them less likely to bring pertussis home to their infant,” Edwards
A new outbreak
What started out as a small pocket of about a dozen patients with
pertussis in one area of Long Island, N.Y., has spread and now includes more
than 200 people, according to the Suffolk County Department of Health Services.
Dennis Russo, MD, director of public health emergency preparedness at
the Suffolk County Department of Health Services, said Suffolk County has the
highest number of cases reported since 2006. However, despite the rise in
cases, Russo said the vaccine is still effective and people in New York should
continue to get the vaccine.
“We have 1.5 million people across the county, and about 210
cases,” Russo said. “Data indicate the vaccine is 80% effective,
which means that everyone should be vaccinated because it is still a very good
vaccine.” – by Colleen Zacharyczuk
For more information:
- Baxter R. #LB-6.
- Daskalaki I. #762.
- Misegades LK. #763.
- Tartof S. #764. All presented at: IDSA 49th Annual Meeting; Oct.
20-23, 2011; Boston.
- Long S. #F2120. Presented at: AAP National Conference and
Exhibition; Oct. 15-18, 2011; Boston.
Disclosure: Dr. Baxter reports receiving research funds from
Sanofi. The other researchers report no relevant financial disclosures.
Will giving Tdap to pregnant women help with the current pertussis
epidemic in California?
Mark H. Sawyer, MD
The switch in strategy will decrease morbidity and mortality related
Pertussis infects people of all ages, but historically, almost all the
deaths are in young infants. As a result, one important goal of our pertussis
immunization strategy is to minimize infection in infants. Where do babies get
their pertussis? From their parents, siblings and grandparents in 75% of the
cases (Bisgard KM. Pediatr Infect Dis J. 2004;23:985-989).
It is unclear how effective the cocooning strategy has been, but what is
clear is that such a strategy is difficult to implement and the potential
benefits have not been fully realized. In trying to immunize all of the family
contacts of a newborn, providers have encountered barriers that include lack of
health care access; inadequate reimbursement; restrictions on outpatient
procedures in inpatient settings; and lack of knowledge about the importance of
vaccine among family members. Health care workers who see young infants are
another potential source of infection, and unfortunately, this group is
inadequately immunized as well.
The ACIP felt that the cocooning strategy was not enough to protect
babies, so the members voted to recommend immunization during pregnancy.
Vaccination during pregnancy appears safe and the concept is that pregnancy
immunization will protect both the mother and the baby from day 1 of life.
There is good evidence that maternal antibody reaches the baby, and it is
likely to protect during the most vulnerable first months of life. The only
concern is that this same maternal antibody may blunt the babys
subsequent response to their own DTaP series. Studies are ongoing to assess the
degree of potential blunting, but in the meantime, ACIP felt it was more
important to protect babies right at birth. Even if blunting occurs, the effect
will be to shift cases that would have occurred in the first month of life to a
later age when pertussis is not fatal. I am sure that this strategy will
decrease deaths from pertussis.
Mark H. Sawyer, MD, is professor of clinical pediatrics and pediatric
infectious disease specialist at the University of California at San Diego
School of Medicine & Rady Childrens Hospital in San Diego.
Disclosure: Dr. Sawyer reports no relevant financial disclosures.
The switch in immunization strategy was necessary and will work if
the blunting dissipates.
The cocoon strategy was designed to immunize adults (and siblings) who
are in close contact with newborn infants, with the most important target being
the parents. Immunizing women immediately postpartum, although recommended, has
been logistically difficult to implement and still may leave infants
susceptible for up to 2 weeks (until the mothers antibody levels rise
Immunization of women during the latter half of pregnancy elicits high
levels of anti-pertussis antibodies, which are then transferred to the fetus
across the placenta. Infants of women immunized during pregnancy have high
levels of antibodies in cord blood, which may help protect them during the
vulnerable first weeks of life, until they produce their own antibodies in
response to the infant immunization series. However, there are preliminary data
that suggest that these high levels of antibody may lead to somewhat lower
levels after the primary immunization series.
The new policy of immunizing women with Tdap during pregnancy may
improve the protection of young infants who are at the greatest risk of severe
disease and death from pertussis. It will be important to closely monitor the
epidemiology of pertussis using active surveillance to determine whether these
beneficial effects are realized and to see whether the potential for lower
antibody levels in the second half of the first year of life has any
detrimental effect on the rates of disease in these older infants.
However, given the dramatic increase in pertussis deaths, the change in
policy was timely and appropriate.
Scott A. Halperin, MD, is professor of pediatrics and head of
pediatric infectious diseases, as well as director of the Canadian Center for
Vaccinology at Dalhousie University in Halifax, Nova Scotia, Canada.
Disclosure: Dr. Halperin reports no relevant financial disclosures.