Download Steedman2015-1090-R1-jebFinal

Maternal Immunization Can Reduce Unnecessary
Maternal and Newborn Deaths
Abstract:
Despite the indisputable successes of the United Nations
Millennium Development Goals, which include goals on improving
maternal health and reducing child mortality, millions of
mothers and newborns still die tragically and unnecessarily
each year. Many of these deaths result from vaccinepreventable diseases, where obstacles such as cost and
accessibility have hampered efforts to deliver efficacious
vaccines to those most in need. Additionally, many vaccines
given to mothers and children under five are not suitable for
newborns, since their maturing immune systems do not respond
optimally during the first few months of life. Maternal
immunization, the process by which a pregnant woman’s immune
system is enhanced against a particular disease and the
protection is then transferred to her unborn child, has
emerged as a strategy to prevent many unnecessary maternal and
newborn deaths. We review vaccines that are already used for
maternal immunization, analyze vaccines under development that
could be used for maternal immunization strategies in the
future, and provide recommendations for policymakers to
1
utilize maternal immunization for improved maternal and
newborn health.
For the past fifteen years, the Millennium Development Goals
(MDGs) have shaped the world’s response to glaring
inequalities in health. These eight international development
goals were established following the Millennium Summit of the
United Nations in 2000 and focus on areas such as eradicating
extreme poverty and hunger, improving education and
environmental sustainability, and combating infectious
diseases.(1) MDGs 4 and 5 focused specifically on reducing
child mortality and improving maternal health,
respectively.(2) Although impressive gains were made in both
of these areas, millions of mothers and children still die
from preventable causes each year.
The mortality rate of children under five decreased by more
than half between 1990 and 2015, from 90 deaths to 43 deaths
per 1000 live births, but did not meet the initial target of a
two-thirds reduction in child mortality.(3) In 2013, over 2.9
million newborns died, representing 44 percent of all deaths
of children under 5.(4) As a consequence, achieving a
reduction in neonatal mortality has remained a major focus of
the global health agenda. Similarly, the global maternal
mortality ratio (the ratio of the number of maternal deaths
per 100,000 live births) decreased by nearly half since 1990,
2
but this fell far short of the goal of reducing the ratio by
three quarters. In 2013, 289,000 women died during pregnancy,
childbirth, or during the 42 days following delivery.(3)
In September 2015, the Sustainable Development Goals (SDGs)
replaced the MDGs as the United Nations’ strategy for
combating health inequalities.(5) Maternal and child health
again feature prominently in this global strategy to achieve
health equality.(6)
The majority of maternal and newborn deaths each year result
from hemorrhage, hypertension, unsafe abortion, complications
from preterm birth, among others.(7) However, vaccinepreventable diseases, including pertussis, tetanus, influenza,
and others are also leading killers of mothers and newborns,
despite widespread distribution of vaccines throughout much of
the world in recent decades. Increased uptake of vaccines for
these diseases, particularly in low- and middle-income
countries, could save the lives of thousands of mothers and
children each year.(8-10)
The World Health Organization (WHO), through its Global
Vaccine Action Plan, has deemed 2011-2020 the Decade of
Vaccines. The Global Vaccine Action Plan framework aims to
extend immunization to everyone by ensuring that adequate
resources are provided for vaccines, health systems and
3
supportive infrastructure, and that more health workers are
trained to reach remote and marginalized populations. The
framework also advocates for the development of new vaccines
and technologies to maximize the benefits of immunization
around the world.(11)
As the Decade of Vaccines passes its halfway point and the
Sustainable Development Goals begin, maternal and newborn
health must be kept at the forefront of global health
policies, programming, and advocacy.
In this article, we synthesize key information from the
literature on vaccines that are currently used, or have the
potential to be used, for maternal immunization. We utilize
this information to provide policy recommendations for
improving global maternal and newborn health.
We first examine the mechanism by which maternal immunization
protects women and newborns, and review maternal immunization
for tetanus, influenza and pertussis.
Mechanism of Maternal Immunization
Immunization during pregnancy can serve two vitally important
purposes: it can actively provide protection against the
infectious disease to the mother and fetus during pregnancy;
4
and pass this protection on to the newborn through infancy.
This occurs through placental transfer of antibodies, a
natural phenomenon that occurs throughout gestation, primarily
in the final four weeks of pregnancy, with protective antibody
levels in the fetus sometimes reaching higher concentrations
than those found in the mother.(8, 9, 12-16)
Without this transfer of immune protection from the mother,
newborns would be even more vulnerable to infectious diseases.
Newborns have to adjust from the tolerogenic in utero
environment to cope with numerous external influences after
birth. Newborns often do not respond well to vaccines and
require multiple doses of vaccines appropriately spaced apart
in time in order to prime their immune system to deal
effectively with a specific infection.
Conversely, a single dose can often immunize a pregnant woman
who has already received a priming course of immunizations in
her youth or has “seen” the disease previously. Most vaccines
are not used in newborns under 6 weeks old, therefore maternal
immunization, which has been shown to passively protect the
baby for the first several months of its life, can limit the
amount of time a newborn lacks immune protection from numerous
infectious diseases.(17, 18) As most pregnant women routinely
seek prenatal care, patient accessibility makes maternal
5
immunization not only a good medical option, but also a
feasible and cost-saving intervention for mutual benefit.(19)
Vaccines Recommended for Use During Pregnancy
Tetanus
Tetanus is caused by the spores of the bacterium Clostridium
tetani, which exists in ubiquitous quantities in soil and
animal intestinal tracts to the extent that it contaminates
numerous surfaces and substances and can never be fully
eradicated.
While tetanus can affect people of all ages, newborns and
their mothers are particularly at high risk for infection if
childbirth occurs under unhygienic conditions. Eliminating
tetanus infections therefore requires immunization and high
quality health services that are universally accessible.(20,
21).
Over 1 million people died from tetanus each year in the
1980s, despite the fact that an effective vaccine, tetanus
toxoid (TT), had been available for decades.(22, 23) As late
as 1988, the WHO estimated that 787,000 of these deaths were
from neonatal tetanus, defined as tetanus in the first 28 days
of life.(21) To decrease the impact of tetanus, in 1989, the
6
42nd World Health Assembly made a global commitment to
eliminate neonatal tetanus, defined as fewer than one case per
1000 live births in all districts.(24) This commitment was
updated in 1999 to include maternal tetanus and renamed the
Maternal and Neonatal Tetanus Elimination Initiative.(21)
As shown in Exhibit 1, by 1994, neonatal tetanus deaths had
decreased to 490,000 per year, and in 2000 had decreased
further to 200,000. The latest data, from 2013, shows that
49,000 neonatal tetanus deaths still occur each year.(20) As
of May 2015, maternal and neonatal tetanus has been eliminated
in all but 22 countries, and overall deaths from tetanus have
been reduced by 94 percent since 1988.(9, 25)
This reduction in tetanus infection was achieved through four
key strategies: delivery of infants by skilled birth
attendants to ensure clean delivery practices; maternal
immunization with tetanus toxoid-containing vaccines;
immunization of women of reproductive age with tetanus toxoidcontaining vaccines in high-risk areas; and surveillance for
neonatal tetanus.(20)
Maintaining this decline in infections and ultimately
eliminating deaths due to tetanus will require sustained
commitment from the international community. Maternal
immunization has played a key role in the progress toward
7
eliminating maternal and newborn tetanus thus far, and
continuing to use it as a strategy will be critical to saving
at-risk maternal and newborn lives. It also provides a
powerful example for the success of the concept of maternal
immunization, which could be applicable to other vaccinepreventable infectious diseases.
Influenza
Pregnant women, new mothers, and newborns are also vulnerable
to influenza infection, which can result in hospitalization,
prematurity, stillbirth, and in rare cases the mother or
newborn’s death.(26-28) Influenza vaccines given during
pregnancy have been shown to produce an immune response during
pregnancy that is passed on to the newborn (29-32) and to
reduce confirmed cases of influenza by up to 63 percent.(17)
As the risk of influenza infection is substantial for pregnant
women, fetuses, and newborns, influenza immunization is
recommended at the beginning of the seasonal influenza
epidemic, independent of the stage of the pregnancy.(33)
Protecting newborns from influenza infection with maternal
immunization is especially important, as influenza vaccination
is not recommended for children younger than 6 months.(34)
8
The effectiveness of maternal immunization, paired with
epidemiological data showing that breastfeeding can protect
against influenza infection in newborns,(35) led the WHO to
recommend in 2005 that all pregnant women be immunized against
influenza.(36) The Surgeon General of the United States
recommended maternal immunization for influenza as far back as
1960,(37) yet low rates of influenza immunization during
pregnancy have persisted. In 2001-2002, a telephone survey
found that only 11.2 percent of pregnant women in the United
States were vaccinated against influenza, although this
steadily increased each year for three years but then
plateaued for three years, reaching 26.9 percent in 20072008.(38) The 2009 influenza A (H1N1) pandemic saw an upsurge
in coverage, and increase has been seen every year since,
leading to a 52.2 percent coverage rate by 2013-2014, and a
decrease in death rate from influenza and pneumonia over this
period, as shown in Exhibit 2.(39)
Given the seasonality of influenza demonstrated in many
resource-rich settings, it is now important to gather
epidemiological data from resource-poor settings through
influenza surveillance to predict the best time to administer
the vaccine during pregnancy, especially as vaccination rates
are often significantly lower in resource-poor settings.(31)
9
However, recent studies suggest that more data is required to
determine the true disease burden of influenza on pregnant
women and newborns. New evidence has shown little to no impact
of maternal influenza virus infection on birth outcomes in
South Africa, whilst it had appeared beneficial in earlier
clinical trials in
Bangladesh. The potential impact of
maternal immunization on mortality or severe disease is
currently unclear.(40)
Despite this, preventing hospitalization through maternal
immunization is still an important public health outcome, and
increasing vaccination rates in all settings should remain an
international priority.
Pertussis
From the 1920s until the widespread adoption of the
diphtheria, pertussis, and tetanus (DPT) vaccine in the 1950s,
between 100,000 and over 250,000 cases of pertussis were
reported in the United States each year. From 1970 until the
early 2000s, pertussis cases dwindled to less than 5,000 per
year typically. However, in the past decade, pertussis cases
have increased, peaking in 2012 with over 48,277 cases
reported, and over 28,000 cases reported in 2013 and 2014.(41)
(Exhibit 3)
10
Similarly, in the United Kingdom, fewer than 1,000 cases were
reported in 2000, but 9367 cases were reported in 2012,
followed by 4621 cases in 2013 and 3388 cases in 2014.(42)
(Exhibit 4) In both the United Kingdom and the United States,
the majority of hospitalizations and deaths occurred in
children under 2 months old, the period when newborns are most
vulnerable to pertussis infection, as the routine immunization
schedule only commences by 2 months of age.(8, 9)
In response to these outbreaks of pertussis, both the United
States and United Kingdom recently updated their
recommendations regarding pertussis vaccinations. The UK’s
Department of Health recommended in September 2012 that all
pregnant women should be offered the pertussis vaccination in
the third trimester of each pregnancy.(43) Since July 2014,
Boostrix IPV, a vaccine against pertussis, polio, diphtheria,
and tetanus, has been given in the United Kingdom, replacing a
similar vaccine, Repevax.(44)
Similarly, the Advisory Committee on Immunization Practices in
the United States recommended in October 2012 that all
pregnant women of 27-36 weeks gestation receive Tdap, an
updated vaccination against tetanus, diphtheria, and
pertussis, during each pregnancy to maximize the transfer of
protective antibody from mother to fetus.(45) However,
questions remain as to whether repeated doses of Tdap are safe
11
and effective for pregnant women, and large-scale studies are
currently underway to provide more data on its safety and
immunogenicity.(46) Additionally, immunity can wane over time
using the Tdap vaccine, which is acellular, meaning that the
vaccine only contains purified components of B. pertussis,
compared to previously used whole-cell vaccines, decreasing
effectiveness and with it the potential for herd immunity.(47,
48)
Although pertussis can affect mothers, newborns are more
vulnerable to severe reactions to infection, including death.
The primary objective in administering the vaccine during
pregnancy is therefore to protect the newborn rather than the
mother, as it will prevent spread of the pertussis organism
from mother to baby.(49)
In 2008, an estimated 16 million cases of pertussis and
195,000 deaths from pertussis occurred globally in children,
making the size and scale of the recent outbreaks in the
United States and United Kingdom pale in comparison.(50)
Deaths in settings where maternal vaccination programs have
been introduced have dropped dramatically. Of the seven deaths
in the United Kingdom in newborn infants in 2013 due to
pertussis, six occurred in infants of unvaccinated mothers,
and the seventh infant’s mother was immunized too late in
pregnancy.(41) Higher rates of maternal immunization worldwide
12
could dramatically decreases the number of cases and deaths
from pertussis.
Safety of Maternal Immunization
Maternal immunization has been used as a strategy to protect
mothers and newborns for decades(51), and numerous studies
have confirmed the safety of vaccines for this purpose.(52-57)
Despite overwhelming data supporting safety of these vaccines,
many pregnant women still refuse to accept maternal
immunization as a preventive strategy against infectious
disease due to fears about safety. Other reasons for refusing
immunization include a perceived low risk of exposure to
particular diseases and a lack of trust in the information
about the vaccine.(58) The lack of encouragement or knowledge
about maternal immunization by health care workers and the
lack of infrastructure to store and distribute vaccines,
particularly in low-resource settings, also contribute to poor
uptake of maternal immunization.(8)
This evidence suggests that a more comprehensive strategy is
required to eliminate misinformation about immunization safety
and efficacy in pregnancy, train health care workers about the
benefits of maternal immunization, and develop the
13
infrastructure required to implement maternal immunization
worldwide.
High-level policy documents such as the WHO’s Global Vaccine
Safety Blueprint are helpful in promoting top-down approaches
in reassuring the public about vaccine safety(59), but more
must be done from the bottom-up to translate policy into
action.
The Future of Maternal Immunization
A number of other vaccines have been used safely and
effectively in adults and children for many years and should
be tested for use in pregnant women, including vaccines
against pneumococcus, Hemophilus influenza Type b, and
meningococcus.(9) Uptake of these vaccines in areas where
these types of infections are endemic could be strategically
advantageous. Clinical trials for the use of the 23 valent
pneumococcal vaccines during pregnancy have been completed,
although results thus far have been inconclusive.(60)
Continuing to test these vaccines for safety and efficacy
should remain a priority.
There are also several new vaccines in the pipeline that have
the potential to be used for maternal immunization. A vaccine
against group B Streptococcus (GBS), the most common cause of
14
bacterial sepsis and meningitis in newborns in high-income
countries and a common cause in low- and middle-income
countries, could be used to prevent infection in newborns when
given to the pregnant woman. (61) Safety and immunogenicity
data are already available from field trials, but more studies
are needed to evaluate the effectiveness of the vaccines.(6264)
Similarly, vaccines under development for respiratory
syncytial virus,(65) herpes simplex virus,(66, 67) and
cytomegalovirus(68) could be transformative for worldwide
maternal and child health, if proven to be safe and effective
for pregnant mothers and their offspring. Maintaining momentum
in developing these vaccines will be paramount to their
successful approval, as it can often take more than 10 years
to develop a fully licensed vaccine, with costs between $200
million and $500 million.(69)
Continued focus on preventing these types of infections should
remain a high priority as the Sustainable Development Goals
gain momentum. In order to further support the prioritization
of maternal and newborn health, we propose the following
recommendations to be considered by policymakers when
developing national and global strategies for saving the lives
of women and children.
15
Policy Recommendations
The MDGs have led to decreases in deaths of mothers and
children worldwide, yet too few countries have reached the
specified targets of MDGs 4 and 5. As a significant proportion
of these deaths are preventable, policymakers should continue
prioritizing the lives of vulnerable mothers and infants in
particular. Global frameworks such as Strategies Toward Ending
Preventable Maternal Mortality (70) and the Every Newborn
Action Plan (4) recommend human rights-based strategies and
set specific targets for reducing national maternal mortality
ratios and ending preventable newborn deaths and stillbirths.
Focusing on essential care during labor, birth, and the first
day and week of life; and integrating maternal and newborn
care are two strategies that could have significant impact.
In addition, vaccines against tetanus, influenza, and
pertussis have been proven to be safe and effective in
preventing infections in mothers and newborns, particularly in
high-income countries such as the United States and the United
Kingdom. Providing these vaccines to pregnant women in lowand middle-income countries should be a priority. The strategy
set out by the Global Vaccine Action Plan should be updated to
emphasize the importance of maternal immunization and set
specific targets for immunization coverage rates in areas
where tetanus, influenza, and pertussis infection are endemic.
16
Vaccines and other drugs often face excessive hurdles during
the path from research to market. When proven to be safe and
effective, vaccines that are given accelerated approval and
market protection could be transformative in saving the lives
of women and newborns in maternal immunization programs.
Innovative strategies that could be implemented to expedite
development and increase uptake include developing publicprivate partnerships for research and development, committing
to advance contracts, patent buyouts or extensions, and tax
credits for vaccine sales, among others.
A number of vaccine candidates exist that could be useful for
maternal immunization. Priority should be given to vaccines
against diseases that weigh considerably in the global burden
of disease and where the potential benefits are high.
Accompanying research and ongoing surveillance should be
supported. However, increasing overall funding for research
and development is only the first step to increased uptake.
Innovative strategies such as diversifying sources of funding
for new vaccines, advocating governments to invest in
immunization in incremental levels according to their ability
to pay, and utilizing differential pricing approaches to pay
for vaccines that are available are all potential pathways to
increased development and uptake of maternal immunization.
17
Conclusion
Maternal immunization has proven to be a safe and effective
strategy for preventing specific infections for many years and
has saved many lives of mothers and newborns. The disease
burden of tetanus, influenza, and pertussis has been minimized
in many countries through maternal immunization, but wider
applications of this strategy are now needed. Millions of
mothers and newborns still die each year from infectious
diseases, particularly in low- and middle-income countries
where vaccines are not as widely distributed or recommended in
maternal immunization programs, or where access to prenatal
care is considerably difficult to achieve. In addition, a
number of other vaccines in the pipeline could potentially be
used in pregnant women, provided they are found to be safe and
effective. As we enter the second half of the Decade of
Vaccines and usher in the Sustainable Development Goals,
maintaining a long-term focus on saving the lives of the most
vulnerable should be the global health community’s primary
focus. Maternal immunization should be a cornerstone of this
strategy.
18
Notes
1.
Dodd R, Cassels A. Health, development and the Millennium
Development Goals. Ann Trop Med Parasitol. 2006 Jul-Sep;100(56):379-87.
2.
Bhutta ZA, Chopra M, Axelson H, Berman P, Boerma T, Bryce
J, et al. Countdown to 2015 decade report (2000-10): taking
stock of maternal, newborn, and child survival. Lancet. 2010
Jun 5;375(9730):2032-44.
3.
United Nations. The Millennium Development Goals Report
2015 [Internet]. New York (NY): United Nations; 2015 July
[cited 2015 Dec 9]. Available from:
http://www.un.org/millenniumgoals/2015_MDG_Report/pdf/MDG%2020
15%20rev%20(July%201).pdf
4.
World Health Organization. Every Newborn: an action plan
to end preventable deaths [Internet]. Geneva (Switzerland):
World Health Organization; 2014 Feb [cited 2015 Dec 9].
Available from:
http://apps.who.int/iris/bitstream/10665/127938/1/978924150744
8_eng.pdf?ua=1
5.
Lu Y, Nakicenovic N, Visbeck M, Stevance AS. Policy: Five
priorities for the UN Sustainable Development Goals. Nature.
2015 Apr 23;520(7548):432-3.
19
6.
Isbell M, Simpson, I. Saving lives, protecting futures:
Progress report on the global strategy for women's and
children's health [Internet]. New York (NY): Every Woman Every
Child, United Nations Foundation; 2015 Mar [cited 2015 Dec 9].
Available from:
http://www.everywomaneverychild.org/images/EWEC_Progress_Repor
t_FINAL_3.pdf
7.
Lassi ZS, Salam RA, Das JK, Bhutta ZA. Essential
interventions for maternal, newborn and child health:
background and methodology. Reprod Health. 2014;11 Suppl 1:S1.
8.
Lindsey B, Kampmann B, Jones C. Maternal immunization as
a strategy to decrease susceptibility to infection in newborn
infants. Curr Opin Infect Dis. 2013 Jun;26(3):248-53.
9.
Chu HY, Englund JA. Maternal immunization. Clin Infect
Dis. 2014 Aug 15;59(4):560-8.
10.
Beigi RH, Fortner KB, Munoz FM, Roberts J, Gordon JL, Han
HH, et al. Maternal immunization: opportunities for scientific
advancement. Clin Infect Dis. 2014 Dec 15;59 Suppl 7:S408-14.
11.
World Health Organization. Global vaccine action plan
2011-2020 [Internet]. Geneva (Switzerland): World Health
20
Organization; 2012 May [cited 2015 Dec 9]. Available from:
http://www.who.int/immunization/global_vaccine_action_plan/GVA
P_doc_2011_2020/en/
12.
Saji F, Samejima Y, Kamiura S, Koyama M. Dynamics of
immunoglobulins at the feto-maternal interface. Rev Reprod.
1999 May;4(2):81-9.
13.
Linder N, Ohel G. In utero vaccination. Clin Perinatol.
1994 Sep;21(3):663-74.
14.
Jones C, Pollock L, Barnett SM, Battersby A, Kampmann B.
Specific antibodies against vaccine-preventable infections: a
mother-infant cohort study. BMJ Open. 2013;3(4).
15.
Jones CE, Naidoo S, De Beer C, Esser M, Kampmann B,
Hesseling AC. Maternal HIV infection and antibody responses
against vaccine-preventable diseases in uninfected infants.
JAMA. 2011 Feb 9;305(6):576-84.
16.
Kampmann B, Jones CE. Factors influencing innate immunity
and vaccine responses in infancy. Philos Trans R Soc Lond B
Biol Sci. 2015 Jun 19;370(1671).
21
17.
Zaman K, Roy E, Arifeen SE, Rahman M, Raqib R, Wilson E,
et al. Effectiveness of maternal influenza immunization in
mothers and infants. N Engl J Med. 2008 Oct 9;359(15):1555-64.
18.
Englund JA, Mbawuike IN, Hammill H, Holleman MC, Baxter
BD, Glezen WP. Maternal immunization with influenza or tetanus
toxoid vaccine for passive antibody protection in young
infants. J Infect Dis. 1993 Sep;168(3):647-56.
19.
Englund J, Glezen WP, Piedra PA. Maternal immunization
against viral disease. Vaccine. 1998 Aug-Sep;16(14-15):145663.
20.
Khan R, Vandelaer J, Yakubu A, Raza AA, Zulu F. Maternal
and neonatal tetanus elimination: from protecting women and
newborns to protecting all. Int J Womens Health. 2015;7:17180.
21.
Roper MH, Vandelaer JH, Gasse FL. Maternal and neonatal
tetanus. Lancet. 2007 Dec 8;370(9603):1947-59.
22.
Stanfield JP, Galazka A. Neonatal tetanus in the world
today. Bull World Health Organ. 1984;62(4):647-69.
23.
Centers for Disease Control and Prevention. Epidemiology
and Prevention of Vaccine-Preventable Diseases. 13 ed.
22
Hamborsky J, Kroger A, Wolfe S, editors. Washington (DC):
Public Health Foundation; 2015.
24.
Expanded programme on immunization. The global
elimination of neonatal tetanus: progress to date. Wkly
Epidemiol Rec. 1993 Sep 17;68(38):277-82.
25.
Maternal and Neonatal Tetanus (MNT) elimination. World
Health Organization; 2015 [cited 2015 11 August]; Available
from:
http://www.who.int/immunization/diseases/MNTE_initiative/en/.
26.
Jamieson DJ, Honein MA, Rasmussen SA, Williams JL,
Swerdlow DL, Biggerstaff MS, et al. H1N1 2009 influenza virus
infection during pregnancy in the USA. Lancet. 2009 Aug
8;374(9688):451-8.
27.
Pierce M, Kurinczuk JJ, Spark P, Brocklehurst P, Knight
M, Ukoss. Perinatal outcomes after maternal 2009/H1N1
infection: national cohort study. BMJ. 2011;342:d3214.
28.
Mosby LG, Rasmussen SA, Jamieson DJ. 2009 pandemic
influenza A (H1N1) in pregnancy: a systematic review of the
literature. Am J Obstet Gynecol. 2011 Jul;205(1):10-8.
23
29.
Puck JM, Glezen WP, Frank AL, Six HR. Protection of
infants from infection with influenza A virus by
transplacentally acquired antibody. J Infect Dis. 1980
Dec;142(6):844-9.
30.
Reuman PD, Ayoub EM, Small PA. Effect of passive maternal
antibody on influenza illness in children: a prospective study
of influenza A in mother-infant pairs. Pediatr Infect Dis J.
1987 Apr;6(4):398-403.
31.
Blanchard-Rohner G, Siegrist CA. Vaccination during
pregnancy to protect infants against influenza: why and why
not? Vaccine. 2011 Oct 6;29(43):7542-50.
32.
Jackson LA, Patel SM, Swamy GK, Frey SE, Creech CB, Munoz
FM, et al. Immunogenicity of an inactivated monovalent 2009
H1N1 influenza vaccine in pregnant women. J Infect Dis. 2011
Sep 15;204(6):854-63.
33.
ACIP Adult Immunization Work Group, Bridges CB, Woods L,
Coyne-Beasley T; Centers for Disease Control and Prevention
(CDC). Advisory Committee on Immunization Practices (ACIP)
recommended immunization schedule for adults aged 19 years and
older--United States, 2013. MMWR Surveill Summ. 2013 Feb 1;62
Suppl 1:9-19.
24
34.
Grohskopf LA, Sokolow LZ, Olsen SJ, Bresee JS, Broder KR,
Karron RA. Prevention and Control of Influenza with Vaccines:
Recommendations of the Advisory Committee on Immunization
Practices, United States, 2015-16 Influenza Season. MMWR Morb
Mortal Wkly Rep. 2015 Aug 7;64(30):818-25.
35.
Howie PW, Forsyth JS, Ogston SA, Clark A, Florey CD.
Protective effect of breast feeding against infection. BMJ.
1990 Jan 6;300(6716):11-6.
36.
H5N1 avian influenza: first steps towards development of
a human vaccine. Wkly Epidemiol Rec. 2005 Aug 19;80(33):277-8.
37.
Burney LE. Influenza immunization: Statement. Public
Health Rep. 1960 Oct;75(10):944.
38.
Kennedy ED, Ahluwalia IB, Ding H, Lu PJ, Singleton JA,
Bridges CB. Monitoring seasonal influenza vaccination coverage
among pregnant women in the United States. Am J Obstet
Gynecol. 2012 Sep;207(3 Suppl):S9-16.
39.
Ding H, Black CL, Ball S, Donahue S, Izrael D, Williams
WW, et al. Influenza Vaccination Coverage Among Pregnant Women
- United States, 2013-14 Influenza Season [Internet]. Atlanta
9GA): Centers for Disease Control and Prevention; 2014 Sep
25
[cited 2015 Dec 10]. Available from:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6337a3.htm
40. World Health Organization. Weekly epidemiological record.
Meeting of the Strategic Advisory Group of Experts on
immunization, April 2015: conclusions and recommendations
[Internet]. Geneva (Switzerland): WHO; 2015 May [cited 2015
Dec 10]. Available from:
http://www.who.int/wer/2015/wer9022.pdf?ua=1
41.
Centers for Disease Control and Prevention. Pertussis.
2015 [cited 2015 18 August]; Available from:
http://www.cdc.gov/pertussis/surv-reporting.html.
42.
Public Health England. Health Protection Report.
2015
[updated 22 May 2015; cited 2015 18 August]; Available from:
https://www.gov.uk/government/uploads/system/uploads/attachmen
t_data/file/429674/hpr1815_prtsss.pdf.
43.
Department of Health. Pregnant women to be offered
whooping cough vaccination.
2012 [cited 2015 18 August];
Available from: https://www.gov.uk/government/news/pregnantwomen-to-be-offered-whooping-cough-vaccination.
44.
Public Health England. Vaccination against pertussis
(whooping cough) for pregnant women-2014: Information for
26
healthcare professionals [Internet]. London: Public Health
England; 2014 July [cited 2015 December 9]. Available from:
https://www.gov.uk/government/uploads/system/uploads/attachmen
t_data/file/338567/PHE_pertussis_in_pregnancy_information_for_
HP_2014_doc_V3.pdf
45.
Centers for Disease Control and Prevention. Updated
Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria
Toxoid, and Acellular Pertussis Vaccine (Tdap) in Pregnant
Women — Advisory Committee on Immunization Practices (ACIP),
2012 [Internet]. Atlanta (GA): Centers for Disease Control and
Prevention; 2013 Feb [cited 2015 18 August]; Available from:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6207a4.htm.
46.
Swamy GK, Beigi RH. Maternal benefits of immunization
during pregnancy. Vaccine. 2015 Sep 16.
47.
Acosta AM, DeBolt C, Tasslimi A, Lewis M, Stewart LK,
Misegades LK, et al. Tdap vaccine effectiveness in adolescents
during the 2012 Washington State pertussis epidemic.
Pediatrics. 2015 Jun;135(6):981-9.
48.
Klein NP, Bartlett J, Fireman B, Rowhani-Rahbar A, Baxter
R. Comparative effectiveness of acellular versus whole-cell
pertussis vaccines in teenagers. Pediatrics. 2013
Jun;131(6):e1716-22.
27
49.
Englund JA. Maternal immunization - Promises and
concerns. Vaccine. 2015 Aug 8.
50.
Pertussis vaccines: WHO position paper. Wkly Epidemiol
Rec. 2010 Oct 1;85(40):385-400.
51.
Glezen WP, Alpers M. Maternal immunization. Clin Infect
Dis. 1999 Feb;28(2):219-24.
52.
Amstey MS, Insel R, Munoz J, Pichichero M. Fetal-neonatal
passive immunization against Hemophilus influenzae, type b. Am
J Obstet Gynecol. 1985 Nov 15;153(6):607-11.
53.
Baker CJ, Rench MA, Edwards MS, Carpenter RJ, Hays BM,
Kasper DL. Immunization of pregnant women with a
polysaccharide vaccine of group B streptococcus. N Engl J Med.
1988 Nov 3;319(18):1180-5.
54.
Sumaya CV, Gibbs RS. Immunization of pregnant women with
influenza A/New Jersey/76 virus vaccine: reactogenicity and
immunogenicity in mother and infant. J Infect Dis. 1979
Aug;140(2):141-6.
55.
Mulholland K, Suara RO, Siber G, Roberton D, Jaffar S,
N'Jie J, et al. Maternal immunization with Haemophilus
28
influenzae type b polysaccharide-tetanus protein conjugate
vaccine in The Gambia. JAMA. 1996 Apr 17;275(15):1182-8.
56.
Shahid NS, Steinhoff MC, Hoque SS, Begum T, Thompson C,
Siber GR. Serum, breast milk, and infant antibody after
maternal immunisation with pneumococcal vaccine. Lancet. 1995
Nov 11;346(8985):1252-7.
57.
O'Dempsey TJ, McArdle T, Ceesay SJ, Banya WA, Demba E,
Secka O, et al. Immunization with a pneumococcal capsular
polysaccharide vaccine during pregnancy. Vaccine. 1996
Jul;14(10):963-70.
58.
Donaldson B, Jain P, Holder BS, Lindsay B, Regan L,
Kampmann B. What determines uptake of pertussis vaccine in
pregnancy? A cross sectional survey in an ethnically diverse
population of pregnant women in London. Vaccine. 2015 Oct
26;33(43):5822-8.
59.
World Health Organization. Global Vaccine Safety
Blueprint [Internet]. Geneva (Switzerland): WHO, 2012 Feb
[cited 2015 Dec 10]. Available from:
http://extranet.who.int/iris/restricted/bitstream/10665/70919/
1/WHO_IVB_12.07_eng.pdf?ua=1
29
60.
Chaithongwongwatthana S, Yamasmit W, Limpongsanurak S,
Lumbiganon P, Tolosa JE. Pneumococcal vaccination during
pregnancy for preventing infant infection. Cochrane Database
Syst Rev. 2015;1:CD004903.
61.
Black S, Margarit I, Rappuoli R. Preventing newborn
infection with maternal immunization. Sci Transl Med. 2013 Jul
24;5(195):195ps11.
62.
Baker CJ, Rench MA, McInnes P. Immunization of pregnant
women with group B streptococcal type III capsular
polysaccharide-tetanus toxoid conjugate vaccine. Vaccine. 2003
Jul 28;21(24):3468-72.
63.
Munoz FM, Ferrieri P. Group B Streptococcus vaccination
in pregnancy: moving toward a global maternal immunization
program. Vaccine. 2013 Aug 28;31 Suppl 4:D46-51.
64.
Madhi SA, Dangor Z, Heath PT, Schrag S, Izu A, Sobanjo-
Ter Meulen A, et al. Considerations for a phase-III trial to
evaluate a group B Streptococcus polysaccharide-protein
conjugate vaccine in pregnant women for the prevention of
early- and late-onset invasive disease in young-infants.
Vaccine. 2013 Aug 28;31 Suppl 4:D52-7.
30
65.
Anderson LJ, Dormitzer PR, Nokes DJ, Rappuoli R, Roca A,
Graham BS. Strategic priorities for respiratory syncytial
virus (RSV) vaccine development. Vaccine. 2013 Apr 18;31 Suppl
2:B209-15.
66.
Roth K, Ferreira VH, Kaushic C. HSV-2 vaccine: current
state and insights into development of a vaccine that targets
genital mucosal protection. Microb Pathog. 2013 May;58:45-54.
67.
Belshe RB, Leone PA, Bernstein DI, Wald A, Levin MJ,
Stapleton JT, et al. Efficacy results of a trial of a herpes
simplex vaccine. N Engl J Med. 2012 Jan 5;366(1):34-43.
68.
Pass RF, Zhang C, Evans A, Simpson T, Andrews W, Huang
ML, et al. Vaccine prevention of maternal cytomegalovirus
infection. N Engl J Med. 2009 Mar 19;360(12):1191-9.
69.
Serdobova I, Kieny MP. Assembling a global vaccine
development pipeline for infectious diseases in the developing
world. Am J Public Health. 2006 Sep;96(9):1554-9.
70.
World Health Organization. Strategies Toward Ending
Preventable Maternal Mortality [Internet]. Geneva
(Switzerland): WHO, 2015 [cited 2015 Dec 10]. Available from:
http://apps.who.int/iris/bitstream/10665/153544/1/978924150848
3_eng.pdf?ua=1
31
Exhibit List
Exhibit 1 (figure)
Caption: Estimated number of deaths worldwide due to neonatal
tetanus, and global coverage with tetanus toxoid vaccine,
1980-2014
Source: Authors’ analysis of data from the sources listed in
the notes below.
Notes: Notes: Numbers of estimated number of deaths due to
neonatal tetanus are denoted by the blue bars and relate to
the left-hand y-axis. Coverage with at least two doses of
tetanus toxoid is denoted by the orange line and relate to the
right-hand y-axis. Estimated number of deaths were retrieved
from the following sources: (1) Roper et al. (Reference 21 in
text) for 1980-1994. (2) Khan et al. (Reference 20 in text)
for 2000-2013. Tetanus toxoid coverage data was retrieved from
the following sources: (1) For 1980-2009: World Health
Organization. WHO vaccine-preventable diseases: monitoring
system. 2010 global summary. Available from:
http://apps.who.int/iris/bitstream/10665/70535/1/WHO_IVB_2010_
eng.pdf (cited 2015 Aug 28). (2) For 2010-2014: World Health
Organization. Global and regional immunization profile. 2015.
Available from:
http://www.who.int/immunization/monitoring_surveillance/data/g
s_gloprofile.pdf?ua=1 (cited 2015 Aug 28).
32
Exhibit 2 (figure)
Influenza immunization rate among pregnant women and death
rate per 100,000 from influenza and pneumonia in the United
States, 2001-2013
Source: Authors’ analysis of data from items listed in the
notes below.
Notes: Influenza immunization rate is denoted by the blue line
and relates to the left hand y-axis. Death rate per 100,000
population from influenza and pneumonia for children under 1
year old is denoted by the orange line and relates to the
right hand y-axis. Influenza immunization rate data was
retrieved from the following sources: (1) Kennedy et al.
(Reference 38 in text) for 2001-2010. (2) Ding et al.
(Reference 39 in text) for 2011-2013. Death rate from
influenza and pneumonia data was retrieved from the Centers
for Disease Control and Prevention. Mortality Multiple Causeof-Death. Available from:
http://www.cdc.gov/nchs/data/nvsr/nvsr64/nvsr64_02.pdf (cited
2015 Nov 4).
Exhibit 3 (figure)
Caption: Number of pertussis cases in the United States, 19222014
33
Source: Author’s analysis of data from items listed in the
notes below.
Notes: Number of pertussis cases in the United States from
1922-2014 is denoted by the blue bars and relates to the left
hand y-axis. Data was retrieved from Centers for Disease
Control and Prevention. Pertussis Cases by Year (1922-2014).
Available from: http://www.cdc.gov/pertussis/survreporting/cases-by-year.html (cited 2015 Nov 4).
Exhibit 4 (figure)
Caption: Number of pertussis cases in the United Kingdom,
1922-2014
Source: Author’s analysis of data from items listed in the
notes below.
Notes: Number of pertussis cases in the United Kingdom from
1974-2014 is denoted by the blue bars and relates to the left
hand y-axis. Data was retrieved from World Health
Organization. Global Health Observatory Data Repository.
Available from:
http://apps.who.int/gho/data/view.main.1540_43?lang=en
(cited 2015 Nov 6).
34