3.1 Polio eradication, global

The Cause67
Poliomyelitis is a paralyzing, sometimes fatal, viraldisease that dates backmore than 3000 years (SeeImage 7 and Image 8).
But the disease was notdescribed in medical literature until 1789. It remained
relatively uncommon until
the 19th century when small
outbreaks began occurring in Europe. By the endof the 19th century, polio
was occurring in epidemics in Europe and North
America. Karl Landsteinerand Eric Popper identified
the causative virus in 1908.
Their discovery paved theway for the development ofa vaccine.

Image 7. Egyptian stele portraying
priest with polio

HTTP://UPLOAD.WIKIMEDIA.ORG/WIKIPEDIA/	  SOURCE:COMMONS/5/5C/POLIO_EGYPTIAN_STELE.JPG	  tive vaccines were alreadyavailable and being widelyused, the World Health
Assembly (WHA), the decision-making body of theWHO, resolved to eradicate
polio from the planet by theyear 2000. At that time, polio had already been virtually eliminated from North
America, Western Europe
and Japan. The goal has
not been achieved, but the
number of cases of polio
is at an all-time low and intense efforts are underway
to achieve the goal as soon
as possible.

Image 9. Bust of Jonas Salk	  The Vaccine

In 1931, Jean Mcnamara
and Frank Burnet discovered that polio was causedby more than one strain of
Image 8. Bilateral polio of the legs
the virus and by 1951 it was
SOURCE: HTTP://WWW.POLIOERADICATION.ORG/
POLIOANDPREVENTION.ASPX
understood that there were
3 types of polio virus: types
1, 2, and 3. This was critical for the development of a protective vaccine. In 1949, John Enders, Thomas Weller andFrederick Robbins won a Nobel Prize for demonstrating how
a virus could be cultured in order to produce a vaccine.

The first polio vaccine wasdeveloped by Jonas Salk
(See Image 9), in 1955.
His vaccine was produced
from inactivated virus. A
live-attenuated oral polio
vaccine was later developed
Image 10. Albert Sabin
by Albert Sabin (See Image
SOURCE: HTTP://UPLOAD.WIKIMEDIA.ORG/WIKIPEDIA/COMMONS/B/B9/ALBERT_SABIN.JPG
10) in 1963. Both vaccines	  were trivalent vaccines
incorporating all three types. The development of safe andeffective vaccines allowed for mass immunization on anational scale. Vaccines made the goal of polio eradication
possible, given that polio is strictly a disease of humans,transmitted directly from one person to another.

The disease is spread by the oral-fecal route (See Figure 56).
The Impact of the Disease
Prior to a vaccine, the US
experienced an average of
20,000 cases of polio annually. By 1988, an estimated 350,000 cases were
occurring annually in 127
countries. Because effec-

70 | VACCINE FACT BOOK 2012	
   FIGURE 56. POLIOVIRUS
REPLICATES IN THE GUT
AND IS TRANSMITTED BY
THE ORAL-FECAL ROUTE

Both vaccines are still in use today. The inactivated vaccine
is widely used in industrialized countries. The live-attenuatedvaccine is primarily used in developing countries.
The impact of the Vaccine
The introduction of a vaccine in 1955 had an almost immediate
effect. Cases of indigenous polio began disappearing
altogether within a few years. Sweden introduced a vaccine
in 1957 and by 1962 had stopped wild polio transmission.

3 Public health effectiveness of vaccine implementation

Iceland introduced a vaccine in 1956 and by 1960 had no
more wild polio. Likewise, in the US, the incidence of polio
fell by 95% between the introduction of a vaccine in 1955
and 1961, in spite of incomplete vaccination coverage (SeeFigure 57)69.

inactivated vaccine

total

1992

1990

1988

1986

1982

1984

1980

1978

1976

1972

1974

1970

1968

1966

1962

1964

1960

1958

1956

1952

1950

1954

1948

oral vaccine

1946

70,00060,00050,00040,00030,00020,00010,0000

1944

Number of Cases

Reported Cases of Polio in the
United States Before and After
Vaccine Introduction

paralytic	
  FIGURE 57. IMPACT OF IMMUNIZATION ON CASES OF POLIO IN THE US

By 1994, 2000, and 2002 wild polio transmission was certified
eliminated in all of the Americas, the Western Pacific, andEurope, respectively70. In 2010 polio was endemic in only four
countries: Afghanistan, India, Nigeria and Pakistan71. Wild
polio type 2 virus has been eradicated, but vaccine-derived
type 2 virus has recently spread in Nigeria. Wild type 1 and3 polioviruses continue to be transmitted in endemic andneighboring countries. By mid-2011, the number of cases
reported globally was approximately 30072 (See Figure 58,
Figure 59, Figure 60). Countries reporting cases in 2011 areshown in Figure 60 and Figure 6173.
Stopping immunization after the spread of polio has beeninterrupted exposes countries to risk. Live-attenuatedvaccine viruses can survive in the environment for a periodof time, and they can spread from human to human. Under
these conditions, live-attenuated vaccine viruses can revert
to their wild form. After immunization ceases, a reverted liveattenuated poliovirus could accidentally be reintroduced into
a population. As a consequence, even after polio has been
globally eradicated, many countries will opt to continue toimmunize indefinitely with an inactivated vaccine.

The economic impact of polio immunization - In theabsence of polio control, the cost of treating polio cases,in the US alone, has been estimated to approach $1
billion annually74. Globally, polio eradication is estimatedto have incremental net benefits of $40–50 billion between
1988 and 203575.

“
Prior to a vaccine,the US experienced
an average of
20,000 cases ofpolio annually. By
1988, an estimated350,000 cases
were occurring
annually in
127 countries.

Sutter RW, Kew OM, Cochi SL. Polio vaccine-live. pp 632. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
Plotkin SA, Vidor E. Polio vaccine-inactivated. pp 620-623. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
69
US Centers for Disease Control and Prevention. MMWR Summary of notifiable diseases, United States, 1993.
http://www.cdc.gov/mmwr/preview/mmwrhtml/00035381.htm
70
Global Polio Eradication. History of Polio. http://www.polioeradication.org/Polioandprevention/Historyofpolio.aspx
71
Global Polio Eradication. Infected countries. http://www.polioeradication.org/Infectedcountries.aspx
72
Global Polio Eradication. Data and monitoring. http://www.polioeradication.org/Dataandmonitoring.aspx
73
Global Polio Eradication. Data and monitoring. Polio this week. http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx
74
Sutter RW, Kew OM, Cochi SL. Polio vaccine-live. pp 643. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
75
Duintjer Debbens RJ, Pallansch MA, Cochi SL, et al. Economic analysis of the global polio eradication initiative. Vaccine 2010; 29: 334-343.
67
68

VACCINE FACT BOOK 2012 | 71

Polio-endemic country
Country in polio-endemic region
No data

Data is projected to 2008 WHO legal template

58. IN 1988, 125 COUNTRIES HAD RECURRING (ENDEMIC) POLIO DISEASE (COUNTRIES IN RED),	  	
  FIGURE
BEFORE AN ACCELERATED IMMUNIZATION ERADICATION PROGRAM BEGAN
Polio-endemic country
Country in polio-endemic region
No data

Data is projected to 2008 WHO legal template

FIGURE 59. IN 2010, ONLY FOUR COUNTRIES CONTINUED TO BE CLASSIFIED AS HAVING RECURRENT (ENDEMIC)POLIO DISEASE (COUNTRIES IN RED)

Wild polio virus type 1
Wild polio virus type 3
Importation countries
Endemic countries

Data at HQ as of 19 July 2011

60. TOTAL NUMBER OF CASES OF POLIO DISEASE IN 2011 (RED DOTS ARE POLIO TYPE 1;
	
  FIGURE
BLUE DOTS ARE POLIO TYPE 3) (COLORED COUNTRIES ARE THE SAME FOUR ENDEMIC COUNTRIES AS IN 2006 AND COUNTRIES WHERE
CASES HAVE BEEN IMPORTED)

72 | VACCINE FACT BOOK 2012

3 Public health effectiveness of vaccine implementation

The Impact of the Disease76, 77, 78

3.2 Haemophilus influenzae type b (Hib)

Prior to immunization, about 3 million cases and 400,000
annual deaths were attributable to Hib globally. Incidence inthe US was 20-88/100,000 children under 5 years of age, orabout 20,000 cases annually, over half of which were casesof meningitis. Incidence was much higher in some Native
American populations, reaching 491/100,000 in children
under 5 years.
In Europe, rates comparable to those of the US were observed.
In Africa, the Pacific Islands, and the Middle East incidenceswere very high. Incidence in the < 1 year age group is thehighest at as many as 200 cases of meningitis/100,000 in
Africa. Case fatality rates from meningitis can be as high as
40%, depending on the setting.
In Asia, incidence has been found to be lower than elsewhere
but some experts believe that this is likely due to masking of
the disease from widespread use of antibiotics.

FIGURE 61. COUNTRIES REPORTING CASES OF POLIO IN 2011
(AS OF JULY 2011)

The Cause
Figure 63 shows reported incidences of Hib disease inchildren under 5 years of age, prior to the introduction of a
vaccine.

Haemophilus influenzae type b (Hib) is a bacteria responsible
for meningitis, pneumonia, and other invasive diseases
particularly in infants and children under 5 years of age (SeeImage 11).
There are six serotypes of the polysaccharide encapsulated
Haemophilus influenza. Type b accounts for 95% of all serious
diseases caused by this organism. Non encapsulated, nontypable forms of the bacteria also exist.
The organism is carried in the pharynx and spread byrespiratory droplets (Figure 62).

FIGURE 62. NASOPHARYNGEAL CARRIAGE AND AEROSOL SPREADOF HAEMOPHILUS INFLUENZAE TYPE B.
SOURCE: CDC PUBLIC HEALTH IMAGE LIBRARY	  Image 11. Purulent meningitis from Haemophilus influenzae type B.
Source CDC Public Health image library

FIGURE 63. INCIDENCE OF HEAM

Chandran A, Watt JP, Santosham M. Haemophilus influenzae vaccines. pp 162. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier,
China, 2008.
77
Hib Initiative. Research and Surveillance. http://www.hibaction.org/research.php#disease_burden
78
Broker M. Burden of invasive disease caused by Haemophilus influenzae type b in Asia. Jpn J Infect Dis 2009; 62: 87-92.
76

VACCINE FACT BOOK 2012 | 73

The Vaccine
The first vaccine developed in the early 1980s was apolysaccharide vaccine. Polysaccharide vaccines do notstimulate lasting immunity in children less than 2 years of age.
In 1987, the first protein conjugate polysaccharide vaccine waslicensed for use in infants. Unlike polysaccharide vaccines,
protein conjugate vaccines stimulate lasting immunity inyoung children. Today there are several licensed protein
conjugate Hib vaccines. One of three different carrier proteins
are used to conjugate (link) with the Hib polyribosylribitol
phosphate (PRP) polysaccharide:•••

tetanus toxoid;
outermembrane protein complex of Neisseria
meningitidis strain B11; ornontoxic variant of diphtheria toxin from
Corynebacterium diphtheria C7 (CRM197).

Conjugate Hib vaccine is now usually provided in combination
with DTP or DTaP containing vaccines.

In the UK, the incidence of disease declined immediately after
the introduction of a vaccine in a 3 dose primary series (SeeFigure 64)81. The incidence rose slightly in the late 1990s, but
has since fallen again since the introduction of a 4th booster
dose at 12 months of age. Most countries deliver three doses
in a primary series. Most industrialized countries also deliver
a booster dose after 12 months of age.

The vaccine has also been found to have an important herd effect (See Figure 12). This is because thevaccine prevents the bacteria from being carried in
the nasopharynx of those individuals vaccinated.
Vaccinated individuals, in addition to
not getting infected, do not spreadthe disease in thecommunity. For thisreason, in settings
where immunization
Image 11. Purulent meningitis from Haemophilus
coverage has been influenzae type B. Source CDC Public Healthless than optimal,
image library: HTTP://PHIL.CDC.GOV/PHIL/DETAILS.ASP?PID=130
declines in incidence of the disease have nevertheless been observed.
Countries that have introduced conjugate
Hib vaccine have eliminated Hib disease as apublic health problem.

FIGURE 64. ALMOST IMMEDIATE IMPACT OF CONJUGATE HIB VACCINEON THE INCIDENCE OF HIB IN < 5 YEARSS-OLDS IN THE UK

The impact of the vaccine
Everywhere the vaccine has been introduced, very rapid
declines of over 90% in the rate of disease have been
observed. In the US, since the introduction of a conjugate Hib
vaccine, the incidence of the disease has declined by 99%79.
African countries where the vaccine has been introduced haveexperienced marked declines in the incidence. The Gambia
has reduced the incidence to 0 from a high of > 200 cases /100,000 in < 1 year-olds (See Figure 10)80.

Wikipedia. Hib vaccine. http://en.wikipedia.org/wiki/Hib_vaccine#Impact
Adegbola RA, Secka O, Lahai G, et al. Ellimination of Haemophilus influenzae type b (Hib) disease from The Gambia after the introduction of routine immunisation
with a Hib conjugate vaccine: a prospective study. Lancet. 2005;366(9480):144-50.
81
McVernon J, Trotter CL, Slack MPE et al. Trends in Haemophilus influenzae type b infections in adults in England and Wales: surveillance study.
BMJ 2004; 329: 655-658.
79
80

74 | VACCINE FACT BOOK 2012

3 Public health effectiveness of vaccine implementation

3.3 Mumps

Complication

Frequency

inflammation of thetesticles (orchitis)

37% post-pubertal men

inflammation of thebreasts (mastitis)

31% post-pubertal women

deafness

0.5-5.0 / 100,000 mumps cases;
1 / 1000 mumps cases in JapanTABLE 15. COMPLICATIONS AND FREQUENCIES OFMUMPS COMPLICATIONS

thought. Deafness was thought to occur in about 0.5 – 5.0 /100,000 cases of mumps. Hashimoto, et al., found the incidence
of deafness from mumps to be approximately 1 / 1000 in Japan83.
In 2005, Kawashima, et al, found that the number of casesof deafness from mumps was steadily increasing in Japan84.
The number of cases in 1987 was estimated at 300, but had
jumped to 650 by 2001. The increase in number of casesof deafness correlated with an increase in the incidence ofmumps.
Complications of mumps are summarized in Table 15.

The Cause82
The Vaccine85
Mumps is a viral disease first described by Hippocrates
in the 5th century BC. The virus was identified by Johnson
and Goodpasture in 1934. The virus most commonly
invades the salivary glands, causing swelling and pain
(See Image 12). It is transmitted by respiratory droplets(See Figure 65).
The Impact of the Disease

The first vaccines from the 1950s were formalin-inactivatedand did not impart lasting immunity. Instead, live-attenuatedvaccines replaced inactivated vaccines in the 1960s. Thirteen
different vaccine strains are produced today in several
different types of cells.
Mumps vaccine is available as a monovalent or in combination
with measles (MM), or measles and rubella (MMR), or measles,
rubella and varicella vaccines (MMRV).

cases / 100 000

Although children are often affected, outbreaks of the disease
are noted to occur commonly in military personnel. In children, in addition to infection of the salivary glands (parotitis),
The impact of the vaccine
the virus can cause lower respiratory disease. In adults, thevirus causes inflammation of thePrior to the use of mumps vaccines,
testicles (orchitis) in 37% of post- 	
  the incidence of the disease was
Incidence of Mumps Before and After the
pubertal men and inflammation
several hundred cases / 100,000
Introduction of a Vaccineof the breasts (mastitis) in 31% of
population with most cases oc800
post-pubertal women.
curring in children from 5–9 years
700
600
of age in industrialized countries.
Denmark
500
In the pre-vaccine era, mumps wasCountries that introduced mumps
Finland400
the leading cause of viral encephavaccine have virtually eliminatedNorway300
litis in the US. Neurological comthe disease. In the US, cases have
Slovenia
200
plications can occur from mumps
declined by more than 98% since100
Swedenencephalitis, including deafness.
the introduction of a vaccine. Other01977 - 1979
1993 - 1995
countries that have used mumps
In Japan, deafness from mumps
vaccine have experienced similar
FIGURE 66. DECLINE IN INCIDENCE OF MUMPS
has recently been found to occur at
declines in cases (See Figure 66)86.
FOLLOWING THE INTRODUCTION OF A VACCINE IN A
a higher incidence than previously
TWO-DOSE SCHEDULE

Plotkin SA, Rubin SA. Mumps vaccines. pp 435-465. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
Hashimoto H, Fujioka M, Kinumaki H et al. An office-based prospective study of deafness in mumps. Pediatr Infect Dis J 2009; 28: 173-5.
84
Kawashima Y, Ihara K, Nakamura M et al. Epidemiological study of mumps deafness in Japan. Auris Nasus Larynx 2005; 32: 125-128.
85
Plotkin SA, Rubin SA. Mumps vaccines. pp 435-465. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
86
Plotkin SA, Rubin SA. Mumps vaccines. pp 440-442. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
82
83

VACCINE FACT BOOK 2012 | 75

The efficacy of mumps vaccines varies by stain, the numberof doses used, and by outbreak settings. In initial clinical trials
with the Jeryl Lynn strain efficacy ranged from 92–96%. Whenstudied in outbreaks (in the US), efficacy has ranged from
78–91%. Efficacy with other strains of vaccine in othercountries has generally been within these ranges.
Mumps vaccines are associated with a very small risk of
aseptic meningitis, which varies by strain and by manufacturer.
But the long-term effects of post-vaccine meningitis are either
very rare or absent. Furthermore, the risk of meningitis fromnatural mumps infection is much higher (1–10%). In Japan,
mumps immunization was found to lower the risk of aseptic
meningitis by 25-fold compared to natural mumps infection87.

3.4 Measles eradication, global

The Cause88
Measles is one of the most contagious viral diseases. It causes
a rash, acute upper respiratory illness, and can lead to complications that can be fatal, especially in children (See Image14). In ancient times, the disease was confused with otherrash-causing diseases, including smallpox. It was recognized
as a separate disease by the end of the 17th century. It wasunderstood to be caused by an infectious agent by the beginning of the 20th century. The disease is spread by aerosol (SeeFigure 67).
The measles virus was first isolated in 1954 by Enders andPeebles and developed into a live-attenuated vaccine by
1963.
The Impact of the Disease89

	
  

	
  

Image 14.
Measles rash. Source:
CDC

FIGURE 67. TRANSMISSION OF MEASLES
VIRUS IS BY AEROSOL ROUTE.
SOURCE: CDC PUBLIC HEALTH IMAGE LIBRARY
HTTP://PHIL.CDC.GOV/PHIL/DETAILS.ASP?PID=8429

In 2000, measles remained the leading cause of death inchildren from a vaccine-preventable disease and the fifth
most frequent cause of all deaths in children under 5 years ofage, killing about 777,000 children every year.
The Vaccine

The case-fatality rate in industrialized countries is about 1–3
deaths / 1000 cases, but is several times higher in developing countries and can reach 15%. In the pre-vaccine era,because of the highly contagious nature of the disease, virtually everyone in industrialized countries was infected withthe measles virus by adolescence. In developing countries, allchildren could be infected by as early as 4 years of age. It wasa leading cause of infant deaths, blindness, and disability.

Measles vaccines are live-attenuated, produced on chickembryo fibroblasts. Unlike polio and some other viruses, there
is a single serotype of measles virus.
Measles vaccines are highly effective (90–95%) against wild
virus. Initially, a single dose in infancy or early childhood wasrecommended in most immunization schedules.

Plotkin SA, Rubin SA. Mumps vaccines. pp 451-452. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
Strebel P, Papania MJ, Dayan GH et al. Measles vaccines. pp 353-398. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China,
2008.
89
Strebel P, Papania MJ, Dayan GH et al. Measles vaccines. pp 358-359. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China,
2008.
mmwrhtml/mm5453a1.htm
87
88

76 | VACCINE FACT BOOK 2012

3 Public health effectiveness of vaccine implementation

600,000
500,000
400,000
300,000
200,000
100,000
0

vaccine licensed

1960
1963
1966
1969
1972
1975
1978
1981
1984
1987
1990
1993
1996
1999
2002
2005

cases

Reduction in Cases of Measles in the US
after Introduction of a Vaccine	
  FIGURE 68. DECLINE IN CASES OF MEASLES IN THE US
AFTER INTRODUCTION OF A VACCINEWith increasing measles control, a second dose of measles
vaccine is now recommended in most immunization schedules, at varying intervals after the first dose. In the US, a firstdose is recommended at 12–15 months and a second doseat 4-6 years of age.
Some countries (Canada, UK, Australia, New Zealand) havealso conducted a one-time nationwide campaign among
school children to reduce the number of persons at risk. Most
industrialized countries also now deliver measles vaccine in
combination with mumps and rubella vaccines MMR (alsolive-attenuated viral vaccines). Most recently, some industrialized countries have introduced a combination vaccine
containing measles, mumps, rubella, and varicella (MMRV)in childhood immunization schedules. Developing countries
often use measles vaccine alone.
Adverse events are mild and commonly include fever and/or rash in 5–15% of recipients (or higher rates with MMR or
MMRV). Evidence does not support any causal relation toirritable bowel syndrome or childhood autism.
The impact of the vaccine
Prior to the introduction of the vaccine, virtually every
child became infected with measles. In the US alone, thisamounted to almost half a million infections every year. Today,
it is estimated that 2.7 million deaths would occur worldwide,
every year, in the absence of measles immunization90. Most

industrialized countries introduced measles vaccines in the
1960s and have since experienced remarkable declines indisease incidence (See Figure 68.)91, 92.
However, because the virus is so highly transmissible, theelimination of wild measles virus requires a 2-dose vaccination strategy. In the Americas, intense efforts in the 1980s and1990s to eliminate measles included mass immunization campaigns to increase immunization coverage and to immunize
the un-immunized or re-immunize the previously immunized.
The economic impact of measles immunization—In theUS, in 2001 dollars, the benefit / cost ratio was estimated at
14.2 for direct costs and 26.0 for indirect costs93. Likewise, inAustralia, economic analyses suggest that measles immunization results in a net benefit to the community of $9.1 billion,
or $8.5 billion to the government94.
The goal of eradication
Because of the high morbidity and mortality associated withmeasles in the absence of immunization, and because of
the excellent benefit / cost ratio for measles immunization,
5 out of 6 regions of the world have set elimination targets
for measles: the Americas by 2000; Europe and Middle Eastby 2010; western Pacific by 2012, and Africa by 2020. The
Americas has achieved a 99% reduction in disease since1990 and the transmission of virus is considered interrupted.
The remaining cases that occur in the Americas are primar-

American Academy of Pediatrics. Why Immunize? http://www.aap.org/advocacy/releases/whyimmunize.htm
Centers for Disease Control and Prevention. Summary of notifiable diseases, United States, 1994. MMWR 1995; 43:1. http://www.cdc.gov/mmwr/preview/
mmwrhtml/00039679.htm
92
Centers for Disease Control and Prevention. Summary of notifiable diseases, United States, 2005. MMWR 2007; 54: 2-92. http://www.cdc.gov/mmwr/preview/
93
Strebel P, Papania MJ, Dayan GH et al. Measles vaccines. pp 359. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
94
Applied economics. Immunisation programs: measles and Hib disease. http://www.appliedeconomics.com.au/pubs/reports/health/ph05.htm
90
91

VACCINE FACT BOOK 2012 | 77

ily from persons who have travelled to the US and spreadtheir infection.
The WHO, in 2003, resolved to halve the deaths from measles
by 2005, by increasing routine immunization coverage anddelivering supplemental immunizations. Now a 2-dose strategy is endorsed for all countries, regardless of economic status or vaccine coverage. The eradication (global elimination)is technically feasible, but will require very high vaccination
coverage to achieve.
Enormous progress toward a goal of eradication has been
made in all regions of the world. Deaths from measles havedeclined by more than 50% (See Figure 69)95.

FIGURE 69. DECLINE IN THE NUMBER OF DEATHS FROM MEASLES
DUE TO INCREASED IMMUNIZATION COVERAGE	  

3.5 Rotavirus

The Cause
Rotavirus is a highly contagious common viral disease spreadby oral-fecal route (See Figure 70).
It is the most common cause of severe diarrhea in infants andyoung children (See Image 15). There are five groups of rotaviruses: A, B, C, D and E. Group A contains animal and human
serotypes (strains). Fourteen G serotypes and several P types
are known to exist but only 6 G serotypes are commonly associated with human disease: G1, G2, G3, G4, G9, and G12.
Each of these G types is further characterized by a P typewhich is numbered. Common types of virus circulating in the
US are P[8]G1, P[4]G2, P[8]G3, P[8]G4, P[8]G9, and P[6]G996.
These viruses multiply in the gut, and transmission of the

Image 15. Child dehydrated from rotavirus diarrhea.
Source: WHO, D Mahalanabis
HTTP://WWW.VACCINEINFORMATION.ORG/ROTAVIRUS/
PHOTOS.ASP	
  disease is from person to person contact—not from contaminated water and food(See Figure 70).

	  The Impact of
the Disease
Rotavirus is the mostcommon cause of severe FIGURE 70. TRANSMISSION OFROTAVIRUS BY FECALE-ORAL ROUTE.
diarrhea
ininfants. SOURCE: CDC PUBLIC HEALTH IMAGE
It is responsible for LIBRARY
2.7 million episodes of HTTP://PHIL.CDC.GOV/PHIL/DETAILS.
ASP?PID=197
illness per year in theUS, and for about $1 billion in direct and indirect costs97.
Globally, rotaviruses kill over 500,000 children every year andaccount for about 25% of deaths from all diarrheal diseases(SEE Figure 71)98. Rotavirus accounts for about 40% of
hospitalization for diarrhea in children under 5 years of age,
and approximately 100 million episodes of diarrhea every
year.
By 2–3 years of age, all children have been exposed torotavirus. In Asia, without rotavirus vaccination, an estimated171,000 children will die of rotavirus by the age of 5 years,

Centers for Disease Control and Prevention. Progress in global measles control and mortality reduction, 2000-2007. MMWR 2008; 57: 1303-1306. http://www.cdc.
gov/mmwr/preview/mmwrhtml/mm5748a3.htm?s_cid=mm5748a3_e
96Centers for Disease Control and Prevention. Prevention of rotavirus gastroenteritis among infants and children recommendations of the Advisory Committee on
Immunization Practices (ACIP)/ MMWR 2009; 58: 1- 25. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5802a1.htm
97
Clark HF, Offit PA, Parashar UD et al. Rotavirus vaccines. pp 715-734. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China,
2008.
98
Tate JE, Patel MM, Steele AD, et al. Global impact of rotavirus vaccines. Expert Rev Vaccines 2010; 9: 395-407
95

78 | VACCINE FACT BOOK 2012

3 Public health effectiveness of vaccine implementation

1.9 million will be hospitalized, and 13.5 million will require an
outpatient visit (See Figure 72)99.
Because rotavirus is equally prevalent in industrializedcountries, vaccines are also important for prevention insettings with good sanitation.
The Vaccine
Rotavirus vaccines are made from either a single strain(monovalent) of live-attenuated human rotavirus (GSK,
Rotarix™) or from five (pentavalent) live-reassortant humanbovine viruses (Merck, RotaTeq™). Both are administeredorally, in two and three doses, given before 24 and 32 weeks,
respectively.

	
  FIGURE 71. GLOBAL BURDEN OF ROTAVIRUS DISEASE	  The first rotavirus vaccine licensed for use in humans wasmade from simian-human reassortant rotaviruses. Carefull
study of adverse events following immunization showed that
this vaccine was associated with a higher risk of the extremelyrare event of intestinal folding (intussusception) (15 cases /1 million children vaccinated). The risk was highest after afirst dose of vaccine. Even though the public health benefits
far exceeded the risks associated with intussusceptions, thesimian-human reassortant vaccine was discontinued becauseof the concerns for liability.

FIGURE 72. IMPACT OF ROTAVIRUS ASIA IN THE ABSENCE
OF IMMUNIZATION

Because of the history of the simian-human reassortantvaccine, the two currently licensed vaccines have been
extensively evaluated for the risk of intestinal intussusception.
Neither vaccine is associated with a higher risk ofintussusceptions (See Table 16).

1 year after
dose 1

Live Reassortant Human-Bovine
Rotavirus

Placebo(n = 34,788)

Live-Attenuated
Human Rotavirus(n = 10,159)

Placebo(n = 10,010)

Intussusception

13

15

4

14

TABLE 16. RISK OF INTUSSUSCEPTION IS NOT ELEVATED FOLLOWING ROTAVIRUS VACCINATION WITH LICENSED LIVEHUMAN-BOVINE REASSORTANT AND HUMAN LIVE-ATTENUATED VACCINES

Podewils LJ, Antil L, Hummelman E, et al. Projected cost-effectiveness of rotavirus vaccination for children in Asia. J Infect Dis 2005; 192: s133-145.

99

VACCINE FACT BOOK 2012 | 79

Adverse events reported from both vaccines are mild andtemporal and include vomiting, diarrhea, and fever. In clinical
trials, these adverse events were reported at similar rates tothose from the placebo groups (See Table 17).

Adverse Event

Live Reassortant Human-Bovine
Rotavirus

PlaceboLive-Attenuated Human
Rotavirus

PlaceboVomiting

4%

3%

8%

8%

Diarrhea

6%

5%

3%

3%

Fever

18%

18%

28%

34%

TABLE 17. COMMON ADVERSE EVENTS FROM ROTAVIRUS VACCINES (SOLICITED WITHIN SEVEN DAYS AFTER THREE DOSES OF
LIVE-REASSORTANT HUMAN-BOVINE ROTAVIRUS; WITHIN EIGHT DAYS AFTER TWO DOSES OF LIVE-ATTENUATED HUMAN ROTAVIRUS) 100, 101

The Impact of the Vaccine
The two currently licensed rotavirus vaccines have excellent
efficacy, ranging from 85 - 98% against rotavirus disease. In
some settings, the vaccines have reduced hospitalizations fordiarrhea of any cause by 42% to 63% in children < 1 year ofage (See Figure 73)103.
The impact of rotavirus vaccines has been almost
immediate in countries where they have been introduced(See Figure 74)104.
Reduction in Diarrhea-Associated Hospitalizations in Panama
Following Introduction of Rotavirus Vaccine
100
75

%

FIGURE 74. REDUCTION IN HOSPITALIZATION RATES FOR
GASTROENTERITIS BY AGE GROUP DURING ROTAVIRUS SEASON IN THE
US, FOLLOWING INTRODUCTION OF ROTAVIRUS VACCINE

	
  

50
25
0
2007
full year

January to June

2008

	
  
FIGURE 73. REDUCTION IN HOSPITALIZATION FOR ANY-CAUSE DIARRHEAIN CHILDREN < 5 YEARS IN PANAMA, FOLLOWING INTRODUCTION OF AROTAVIRUS VACCINE IN 2006

Merck. RotaTeq prescribing information. July 2011. http://www.merck.com/product/usa/pi_circulars/r/rotateq/rotateq_pi.pdf
GSK Source. Rotarix prescribing information. February 2011. https://www.gsksource.com/gskprm/en/US/adirect/gskprm?cmd=ProductDetailPage&product_id=1
244173585205&featureKey=600594#nlmhighlights
102
Sirica C and Wuethrich B. Roatvirus: interesting facts about a virus on the rise. Micobiowiki. Jan 9, 2009. http://microbiowiki.wetpaint.com/page/Rotavirus%3A+Interesting+facts+about+a+virus+on+the+rise
103
Molto Y, Cortes JE, de Oliveira LH et al. Reduction of diarrhea-associated hospitalizations among children aged < 5 years in Panama following the introduction ofrotavirus vaccine. Pediatr Infect Dis J 2011; 30: s16-s20.
104
Curns AT, Steiner CA, Barrett M et al. Reduction in acute gastroenteritis hsopitalizations amond US children after introduction of rotavirus vaccine: analysis of
hospital discharge data from 18 US states. JID 2010; 201(11):1617-1624.
100
101

80 | VACCINE FACT BOOK 2012

3 Public health effectiveness of vaccine implementation

Marked declines in the incidence of rotavirus disease havebeen observed in the seasons following rotavirus vaccine
introduction in both Latin America105 and Europe106 andAustralia107 and the US108 (See Table 18).

Country

ImpactVaccine Effectiveness

Australia• 45% reduction in proportion of positive rotavirus tests in 2007;• 43%reduction in proportion of positive rotavirus tests in 2008;• 75% reduction in rotavirus hospitalizations in New South Wales in 2008-2009• 85% against rotavirus infections;• 89.3% efficacy against rotavirus
infections in Queensland

Austria• 74% reduction in rotavirus-associated hospitalizations• 61–98%

Belgium• 65% reduction in mean hospitalization days from rotavirus gastroenteritis in
2007-2008;• 83% reduction in mean hospitalization days from rotavirus gastroenteritis in
2008-2009;• 50% reduction of rotavirus infections in 2008–2009;• 75% reduction in rotavirus positive gastroenteritis

Mexico• 42% reduction in any-cause diarrhea mortality;• 11% reduction in diarrhea-associated hospitalizations in 2007;• 40% reduction in diarrhea-associated hospitalizations in 2009

El Salvador• 79% reduction of rotavirus diarrhea;• 81% reduction in rotavirus-associated hospitalization in < 5 years in 2008;• 48% reduction in diarrhea-associated health visits during rotavirus season in 2008;• 35% reduction in diarrhea-associated health visits during rotavirus season in 2009;• 69% reduction in rotavirus-associated hospitalization

Nicaragua• 23% reduction for any-cause diarrhea

Panama

• 22% reduction in diarrhea-associated hospitalizations in < 5 years in 2007
(37% for Jan–Jun);• 37% reduction in diarrhea-associated hospitalizations in < 5 years in 2008(58% for Jan–Jun)

US• 60% reduction in peak proportion of positive rotavirus tests in 2007–2008;• 42% reduction in peak proportion of positive rotavirus tests in 2008–2009;• 82% reduction in proportion of positive rotavirus tests in 2009–2010;• 16% reduction in hospitalization rates for any-cause diarrhea in < 5 years in 2007;• 46% reduction in hospitalization rates for any-cause diarrhea in < 5 years in 2008

• 74% against severe and 88%
against very severe rotavirus
gastroenteritis• 52–63% against severe rotavirus
gastroenteritis;• 73–86% against very severe
rotavirus gastroenteritis

TABLE 18. IMPACT OF ROTAVIRUS IMMUNIZATION IN SELECT COUNTRIES106, 107, 108, 109, 110, 111, 112, 113

De Oliveira LH, Danovaro-Holliday C, Sanwogou NJ, et al. Progress in the introduction of the rotavirus vaccine in Latin America and the Caribbean – four years ofaccumulate experience. Pediatr Infect Dis J 2011; 30: s61-s66.
106
Braeckman T, Herck KV, Raes M, et al. Rotavirus vaccines in Belgium – policy and impact. Pediatr Infect Dis J 2011; 30: s21-s24.
107
Buttery JP, Lambert SB, Grimwood K, et al. Rediction in rotavirus-associated acute gastroenteritis following introduction of rotavirus vaccine into Australia’s
national childhood vaccine schedule. Pediatr Infect Dis J 2011; 30: s25-s29.
108
Tate JE, Cortese MM, Payne DC, et al. Uptake, impact, and effectiveness of rotavirus vaccination in the United States – review of the first three years of postlicensure
data. Pediatr Infect Dis J 2011; 30: s56-s60.
109
Tate JE, Patel MM, Steele AD, et al. Global impact of rotavirus vaccines. Expert Rev Vaccines 2010; 9: 395-407.
110
Tate JE, Mutuc JD, Panozzo CA, et al. Sustained decline in rotavirus detections in teh United States following the introduction of rotavirus vaccine in 2006. Pediatr
Infect Dis J 2011; 30: s30-s34.
111
Molto Y, Cortes JE, de Oliveira LH et al. Reduction of diarrhea-associated hospitalizations among children aged < 5 years in Panama following the introduction ofrotavirus vaccine. Pediatr Infect Dis J 2011; 30: s16-s20.
112
Quintanar-Solares M, Yen C, Richardson V, et al. Impact of rotavirus vaccination on diarrhea-related hospitalizations among children < 5 years of age in Mexico.
Pediatr Infect Dis J 2011; 30: s11-s15.
113
Yen C, Armero Guardado JA, Alberto P, et al. Decline in rotavirus hospitalizations and health care visits for childhood diarrhea following rotavirus vaccinations in El
Salvador. Pediatr Infect Dis J 2011; 30: s6-s10.
105

VACCINE FACT BOOK 2012 | 81

As of 2010, 14 countries in Latin America were using rotavirus
vaccines114. Post licensure efficacy trials have confirmed
efficacy in Latin American countries. When co-administeredwith oral polio vaccine in six Latin American countries, vaccine
efficacy was found to be 81% against severe diarrhea andvomiting (gastroenteritis)115.
Image 16. President Bolanos of Nicaragua adminisering afirst dose of rotavirus vaccine.
Source: Merck Vaccines

Impact of Rotavirus Immunization in Nicaragua	
  In 2005, the health system in Nicaragua had been overwhelmed by an outbreak of rotavirus disease. The country
reported over 64,000 cases of diarrhea (from any cause) and 56 deaths from diarrhea116. In 2006, in partnership withMerck, Unicef, and international health organizations, rotavirus vaccine was introduced for the first time in a developing
country. For three years, Merck donated rotavirus vaccine for all infants in Nicaragua.
President Enrique Bolaños administered the first dose of oral vaccine on October 27, 2006117. The vaccine has sinceprevented 77% of very severe cases of rotavirus diarrhea118 in Nicaragua and cut hospital admissions and emergency
room visits by 50%119. In children less than 1 year of age, vaccine was 88% effective against hospitalization fromrotavirus gastroenteritis120.

3.6 Human Papillomavirus (HPV)The Cause
Human Papillomaviruses (HPV) were originally thought tobe benign wart-causing viruses. But in the 1980s, the Nobel
Prize winning Harald zur Hausen hypothesized that HPVs
were likely the cause of cervical cancer.
HPV commonly infects humans and can cause warts andcancers. The virus is made up of two proteins (L1 and L2)
which are assembled in pentameres (See Figure 75).

	
  

L1	
  
L1	
  

	
  
	
  
	
  

L1	
  
L2	
  

L1	
  

L1	
  

FIGURE 75. SINGLE PENTAMERE OF HUMAN PAPILLOMAVIRUS(WHOLE VIRUS HAS 72 PENTAMETERS)De Oliveira LH, Danovaro-Holliday C, Sanwogou NJ, et al. Progress in the introduction of the rotavirus vaccine in Latin America and the Caribbean – four years ofaccumulate experience. Pediatr Infect Dis J 2011; 30: s61-s66.
115
Tregnaghi MW, Abate HJ, Valencia A, et al. Human rotavirus vaccine is highly efficacious when coadministered with routine expanded program of immunization
vaccines including oral poliovirus vaccine in Latin America. Pediatr Infect Dis J 2011; 30: e103-108. http://www.ncbi.nlm.nih.gov/pubmed/21378594
116
Merck. Nicaraguan vaccination program. http://www.merck.com/responsibility/access/access-feature-nicaraguan.html
117
PATH Rotavirus Vaccine Project - Summary Report. http://www.rotavirusvaccine.org/files/RVP_SummaryReport_Final.pdf
118
View Change.Org. Living proof: Nicaragua – a vaccine’s remarkable impact. http://www.viewchange.org/videos/living-proof-nicaragua-a-vaccines-remarkableimpact
119
PATH. Press Room. New evidence on rotavirus vaccines in Asia demonstrate significant protection against the most common deadly form of childhood diarrhea.
Press release. http://www.path.org/news/pr100805-rotavirus-vaccines-Asia.php
120
Mast TC, Espinoza F, Palacio del Carmen L, et al. Effectiveness of the oral pentavalent rotavirus vaccine in Nicaragua. Poster presentation 28th annual meeting of
the European Society for Pediatric Infectious Diseases. May 4 – 8, 2010. http://www.kenes.com/espid2010/posters/Abstract596.htm
114

82 | VACCINE FACT BOOK 2012

3 Public health effectiveness of vaccine implementation

About 80% of women in the US will be infected by at least
one strain of HPV by 50 years of age. There are about 200
types of HPV. More than 40 types cause genital infections.
Types 16 and 18 are now known to cause 70% of cervicalcancers and the majority of genital cancers (See Figure 77).
Types 6 and 11 cause 90% of genital warts. These virus types
are transmitted sexually (See Figure 78).

	  HPV may be cleared by the immune system quickly (weeks ormonths) after infection. But sometimes the virus persists fora long period of time (up to 10 years). It is in these persons
that normal cells may be transformed into cancerous cells.
These transformations occur because viral proteins (E6 andE7) inactivate human tumor suppressor proteins.

FIGURE 72. IMPACT OF ROTAVIRUS ASIA IN THE ABSENCE
OF IMMUNIZATION

Based on their characteristics, HPVs are classified into
four groups. Each group may include several types(See Table 19)121.

Group

Site

Effects

Cancer-causing

Common HPV Types

Benign skin

skin

warts

no

1, 2

Epidermodysplasia
verrucruciformis

skinflat warts

yes

5, 8

Genitalgenitalswarts

no (but can cause precancerous lesions)6, 11High-risk genital

genitalsflat warts

yes (can also cause precancerous lesions)16, 18, 33, 45

TABLE 19. CLASSIFICATION OF HPVs (ADAPTED FROM VACCINES 5TH EDITION)	
  Proportion of High-Risk HPVs by Type
60
50
40
% 30
20
10
0
HPV HPV HPV HPV HPV HPV HPV HPV
16
18
31
33
35
45
52
58

	
  

FIGURE 77. GENITAL AND HIGH-RISK GENTIAL
HPVs ARE TRANSMITTED SEXUALLY. SOURCE: NIH-

FIGURE 78. GLOBAL DISTRIBUTION OF HIGH-RISK HPVs BY TYPE(VALUES ARE APPROXIMATE)

VISUALS OLINE. LABORATORY OF TUMOR VIRUS BIOLOGY

Schiller JT, Frazer IH, Lowy DR, et al. Human papillomavirus vaccines. pp 246. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier,
China, 2008.
121

VACCINE FACT BOOK 2012 | 83

The Impact of the Disease122

The Vaccine127

Globally, cervical cancer is the 2nd or 3rd most common cancer
in women, depending on the country screening practices.
It results in 273,000 deaths / year or 2.7 million years of life
lost123. In Latin America and Eastern Europe, this represents
more life years lost than from tuberculosis and AIDS.

A vaccine for use in humans was developed by using theL1 protein which makes up the shell (capsid) of the virus(See Figure 75). The star shaped L1 proteins (pentameres) self
assemble into virus-like particles (VLPs). The L1 protein canbe produced from a number of cell lines. Currently licensed
vaccines are produced in insect cells or in yeast. Since thevaccine is made from the L1 protein only (and not from thewhole virus) the vaccine is not infectious and cannot cause
cancer-like HPVs.
The two vaccines licensed for use are:

About 70% of young women who become sexually active will
become infected with one or more types of HPV within five
years. About 52–58% of cervical cancers are caused by HPV

Age-related incidence of cervical cancer in the
US

•

20

•

15
10
5
85+

80-84

75-79

70-74

65-69

60-64

55-59

50-54

45-49

40-44

35-39

30-34

25-29

20-24

0
15-19

cases / 100,000	
  years of age
FIGURE 79. AGE-RELATED INCIDENCE OF CERVICAL CANCER IN THE US

type 16, depending on the region. Up to an additional 20%
are caused by HPV type 18. The remainder are caused mostly
by types 31, 33, 35, 45, 52, and 58 (See Figure 78)124.
The incidence of cervical cancer varies considerably, even
within a country. Incidence tends to be higher in developing
countries or in minority populations. Incidence peaks in the
40–44 year age group, in the US (See Figure 79)125. In 2011,about 12,710 new cases of cervical cancer and about 4,290
deaths are expected to occur in the US126.

a bivalent vaccine (types 16 and 18, Cervarix™ from
GSK); and,a quadrivalent vaccine (types 6, 11, 16, and 18,
Gardasil ™ from Merck).

Both vaccines are injectable and given in three doses over
six months. Because vaccines prevent infection and the rateof infection increases rapidly within the first years of sexual
activity, vaccination is focused on girls before they become
sexually active. In the US, the ACIP recommends vaccination
at 11–12 years of age, and up to 26 years of age for catch-up
immunization. In addition to the prevention of cervical cancer,
the quadrivalent vaccine, Gardasil™, is also approved forprevention of vulvar or vaginal cancers in females and for theprevention of genital warts, anal cancers, and precancerous ordysplastic lesions in females and males 9–26 years of age128.
The Impact of the Vaccine
In clinical trials, both vaccines proved highly effective (94–96%)
at preventing persistent infections against corresponding
HPV types. Both vaccines were nearly 100% effective atpreventing cervical intraepithelial neoplasia (CIN) (a precursor
to cervical cancer)129.

Schiller JT, Frazer IH, Lowy DR, et al. Human papillomavirus vaccines. pp 243-257. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders
Elsevier, China, 2008.
123
World Health Organization. Human papillomavirus and HPV vaccines: technical information for policy-makers and health professionals. Department of Immunizations,
Vaccines and Biologicals. 2007. http://whqlibdoc.who.int/hq/2007/WHO_IVB_07.05_eng.pdf
124World Health Organization. Human papillomavirus and HPV vaccines: technical information for policy-makers and health professionals. Department of Immunizations,
Vaccines and Biologicals. 2007. http://whqlibdoc.who.int/hq/2007/WHO_IVB_07.05_eng.pdf
125
National Cancer Institute. Surveillance Epidemiology and End Results. SEER Cancer Statistics Review 2004-2008. http://seer.cancer.gov/csr/1975_2008/browse_
csr.php?section=5&page=sect_05_table.07.html
126
National Cancer Institute. Cervical cancer. http://www.cancer.gov/cancertopics/types/cervical
127
Schiller JT, Frazer IH, Lowy DR, et al. Human papillomavirus vaccines. pp 243-257. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders
Elsevier, China, 2008.
128
MerckVaccines.com. Gardasil indications. http://www.merckvaccines.com/Products/Gardasil/Pages/indications.aspx
129
Schiller JT, Frazer IH, Lowy DR, et al. Human papillomavirus vaccines. pp 243-257. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders
Elsevier, China, 2008.
122

84 | VACCINE FACT BOOK 2012

3 Public health effectiveness of vaccine implementation

Country

Year added toimmunization schedule

Australia

2007

girls and women 12-26 years for an initial period of three years;
routine for girls 12-13 years;

Canada2007

routine for girls 11-14 years

France2007

voluntary for girls and women 14-23 years not sexually active or sexually active < 1 year

Greece2007

mandatory for girls entering grade 7;
available to girls and women 12 – 26 years

New Zealand2008

girls and women born after 1990;
routine for girls in grade 8 or 12 years of age

Norway2009

routine for girls 12-13 years

Sweden2010

voluntary for girls 10-12 years

United Kingdom

2008

routine for girls 12-13 years;
catch-up for girls up to 18 years of age

United States2007

routine for girls 11–12 years;
catch-up for girls and women 13–26 years;
boys 9–26 years (2010)

Immunization schedule

TABLE 20. COUNTRIES WITH HUMAN PAPILLOMAVIRUS VACCINE IN IMMUNIZATION SCHEDULES130

On the basis of clinical trial data, several countries introduced
HPV vaccine into national immunization programs shortly
after they were licensed (See Table 20).
Preventing persistent infection with HPV is presumed to resultin an important reduction in the incidence of cervical cancer.
But this effect will only be observed at some point in the
future because the time required to develop cervical cancer
is 10 or more years. Nevertheless, countries that have already

implemented HPV immunization programs may already beobserving some reductions in incidence in vaccine-eligible
age groups. A study in Australia found that incidence of highgrade abnormalities in girls < 18 years had decreased by 38%
three years after vaccine introduction131, and the prevalenceof genital warts in the vaccinated population has decreasedby 59%132. Evidence is growing for the ability of vaccine
HPV types to cross-protect against some other high-risk
HPV types.

Wikipedia. HPV vaccine. http://en.wikipedia.org/wiki/HPV_vaccine
Brotherton JML, Fridman M, May CL, et al. Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study.
Lancet 2011; 377: 2085-2092.
132
Donovan B, Franklin N, Guy R, et al. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillancedata. Lancet Infect Dis 2010; 11:39-44.
130
131

VACCINE FACT BOOK 2012 | 85

Impact of HPV Vaccination in Australia
Australia introduced HPV vaccine in 2007. Between 2007 and 2009 Australia conducted a national catch-up campaign.
72% of girls aged 14 and 15 and nearly 66% of girls aged 16 and 17 were vaccinated with three doses133.
Australia now routinely administers vaccine to 12- and 13-year-old girls in their high school vaccination program.
Vaccines are provided at no cost to girls and approved for boys 9-15 years of age.
The National HPV Vaccination Program Register monitors the impact on cervical cancer rates and vaccination coverage,
and provides reminders for full immunization.
Because cervical cancer usually occurs several years after infection, the full impact on the incidence of cervical cancer
cannot be measured for several years. Nevertheless, the age-adjusted incidence of HPV type 16 was expected to havedecreased by 56% from pre-vaccine levels, by 2010. By 2050 a 92% reduction in incidence of HPV type 16 infections
is expected134, 135.
How the reduction in infections will impact cervical cancer is difficult to assess. Not all infections result in cancer, andthe measured incidence of cervical cancer depends on the quality of a screening program. But already high-grade
cervical abnormalities in girls < 18 years have decreased by 38%, three years after vaccine introduction136. And theprevalence of genital warts in the vaccinated population has decreased by 59%137.

	
  Australian Government. Department of Health and Ageing. Human Papillomavirus (HPV).
http://www.health.gov.au/internet/immunise/publishing.nsf/Content/immunise-hpv
134
Cancer Council. Questions and Answers: New research on HPV: HPV infections will plummet by 2010.
http://www.cancer.org.au/File/NewsMedia/MediaReleases2008/CERUresearchHPVQ&A.pdf
135
Smith MA, Canfell K,Brotherton JML, et al. The predicted impact of vaccination on human papillomavirus infections in Australia. Intl J Cancer 2008; 123: 18541863.
136
Brotherton JML, Fridman M, May CL, et al. Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study.
Lancet 2011; 377: 2085-2092.
137
Donovan B, Franklin N, Guy R, et al. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillancedata. Lancet Infect Dis 2010; 11:39-44.
133

86 | VACCINE FACT BOOK 2012

VACCINE FACT BOOK 2012 | 87

3.7 Pneumococcal disease

The Cause	
  Pneumococci are bacteria(Streptococcus
pneumoniae) that can inhabit (colonize) the nasopharynx inhumans, but normally do
Figure 80. Pneumococci colonize
not cause disease. Occathe back of the nose. When theysionally these bacteria may
spread to other organs in the bodyspread to the ears, lungs,
they cause illness.
SOURCE: CDC PUBLIC HEALTH IMAGE LIBRARY HTTP://brain, or other organs in
EN.WIKIPEDIA.ORG/WIKI/FILE:PNEUMOCOCCUS_CDC_
PHIL_ID1003.JPG
the body (Figure 80). The
spread of the bacteria may
be localized in the respiratory tract and cause ear or sinus infections. If it spreads beyond, it causes invasive pneumococcal disease (IPD). The disease varies according to the organs
that are affected. Typically IPD manifests as blood poisoning(bacteremia), pneumonia, or meningitis. The young and theelderly are most often affected.
Pneumococci were first
identified in 1881 and wererecognized as cause of lobar pneumonia (See Image17). Today, pneumococci
have been classified in more
Image 17. Chest X-ray showing
than 90 serotypes based onpneumococcal lobar pneumonia
differences in a polysaccharide capsule that surrounds
them. The polysaccharide capsule plays a role in virulence
and in how the bacteria are processed by the immune system. Some serotypes account for more invasive disease thanothers. The top 20 serotypes account for the majority of disease cases.
Pneumococcal infections can be treated with antibiotics, but
in recent years antibiotic-resistant strains of pneumococci
have emerged. Because of their frequency and because of

the severity of the diseases that they cause, pneumococcal
infections are best prevented by immunization.
The Impact of the Disease
Pneumococcal disease is widespread throughout the world,
and is the most important cause of bacterial meningitis,
pneumonia, and ear infections (otitis media) in the US andin many other countries. Nearly everyone will experience apneumococcal infection during childhood.
Pneumococcal disease can complicate viral infections suchas measles or influenza138. Increases in pneumococcal
disease are observed during influenza outbreaks.
Globally, acute respiratory infections account for almost
2 million deaths in children every year, and 1 million deaths
are from pneumococcal pneumonia in children < 5 years
old139. Most other serious cases of pneumococcal disease
occur in persons 50 years and older.
Prior to childhood immunization in the US, 500,000 episodesof pneumococcal pneumonia137 and 63,000 cases of invasive
pneumococcal disease were estimated to have occurredannually140. About 17,000 of these cases occurred in children
under 5 years of age141. The US experienced about 6,100
deaths from invasive pneumococcal disease each year. About
700 cases of meningitis and 200 deaths occurred annually inchildren under 5 years of age (See Table 21).
The incidence of invasive pneumococcal disease is highest in
infants and young children. Table 22 shows the incidence ratesof IPD in select countries before childhood pneumococcal
vaccines were introduced. Differences in surveillance systems
and diagnostics between, or within, countries may accountfor some of the variation seen.

National Foundation for Infectious Diseases. Facts about pneumococcal disease. http://www.nfid.org/factsheets/pneumofacts.shtml
Black S, Eskola J, Whitney C, et al. Pneumococcal conjugate and pneumococcal common protein vaccines. pp 531-567. In Vaccines 5th edition, S Plotkin, W
Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
140
Centers for Disease Control and Prevention. What would happen if we stopped vaccinations? Pneumococcal.
http://www.cdc.gov/vaccines/vac-gen/whatifstop.htm#pneumo
141
Centers for Disease Control and Prevention. Preventing pneumococcal disease among infants and young children. Recommendations of the Advisory Committee
on Immunization Practices (ACIP). MMWR 2000; 49 (RR-9): 1 – 35.
142
Centers for Disease Control and Prevention. Pneumococcal disease and pneumococcal vaccines. May 2009.
www.cdc.gov/vaccines/pubs/pinkbook/downloads/Slides/Pneumo11.ppt
138
139

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3 Public health effectiveness of vaccine implementation

Syndrome

number of cases annuallybacteremia

1,300

meningitis

700

death

200

ear infection (otitis media)

5,000,000

TABLE 21. FREQUENCY OF PNEUMOCOCCAL SYNDROMES IN THE US
IN CHILDREN < 5 YEARS, PRIOR TO CHILDHOOD PNEUMOCOCCALIMMUNIZATION142

Country

periodincidence in < 2 years of age

incidence in < 5 years of age

Japan (Chiba Prefecture)

2003 – 2006

19.5 – 23.8

12.6 – 13.8

Japan (Kamikawa and Soya
sub-prefectures)2000 – 2010

79.2

43.1

UK

1980 – 1999

37.8

20

Spain

1988 – 2001

93.5

55.3 – 58.8

Mozambique

2001 – 2003

US

1998

416
167

100

TABLE 22. INCIDENCE OF INVASIVE PNEUMOCOCCAL DISEASE IN YOUNG CHILDREN IN SELECT COUNTRIES143,144,145,146,147

In addition, some ethnic groups may be particularly vulnerable(See Table 23).

Age (years)

incidence (cases / 100,000) US General Population

incidence (cases / 100,000) US Navajo and Apache

<2

167

2,396

2–4

36

227 (2 – 5 years)

5–9

6

54

10 – 19

3

35

TABLE 23. INCIDENCE OF INVASIVE PULMONARY DISEASE IN CHILDREN IN THE US IN 1998, PRIOR TO THE INTRODUCTION OF A CHILDHOOD
PNEUMOCOCCAL VACCINE148

Sakata H. Invasive Streptococcus pneumoniae infections in children in Kamikawa and Soya subprefecture, Hokkaido, Japan, 2000-2010, before the introductionof 7-valent pneumococcal conjugate vaccine. J Infect Chemother 2011; DOI: 10.1007/s10156-011-0264-8
144
Bernaola Iturbe E, Aristequi Fernandez J, Herranz Aquirre M, et al. Study of the incidence of invasive pneumococcal disease in neonates and children aged lessthan 5 years in the Basque country and Navarre [Spain]. An Esp Pediatr 2002; 57: 301-309.
145
Roca A, Sigauque B, Quinto LI, et al. Invasive pneumococcal disease in children < 5 years of age in rural Mozambique. Trop Med Intl Health 2006; 11:1422-1431.
146
Ispahani P, Slack R, Donald F, et al. Twenty year surveillance of invasive pneumococcal disease in Nottingham: serogroups responsible and implication fro
immunization. Arch Dis Child 2004; 89: 757-762.
147
Ishiwada N, Kurosaki T, Terashima I, et al. Incidence of pediatric invasive pneumococcal disease in Chiba prefecture, Japan (2003-2006). J Infect 2008; 57:
455-458.
148
Centers for Disease Control and Prevention. Preventing pneumococcal disease among infants and young children. Recommendations of the Advisory Committee
on Immunization Practices (ACIP). MMWR 2000; 49 (RR-9): 1 – 35.
143

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Next to the very young, the elderly experience the highest
incidence of invasive pneumococcal disease (IPD). In 19981999, incidence rates in the US were 40.8 / 100,000 for
persons 50 years and over, 61.5 / 100,000 for persons 50 – 64
years, and 61.5 / 100,000 for persons > 65 years.

In 2010, a 13-valent conjugate pneumococcal vaccine waslicensed. It contains types 3, 6A, and 19A in addition to thetypes contained in the 10-valent vaccine.

Mortality rates from IPD in the US are approximately 7–28%
for all age groups and as high as 11–44% for the elderly149.
Case-fatality rates for pneumococcal meningitis can reach
40% and cause permanent injury in 30–50% of cases.

Pneumococcal polysaccharide vaccine has been shownto significantly reduce the risk of invasive pneumococcal
disease in immunocompetent adults. Some studies haveshown the vaccine to have an effectiveness of about 75%,
although the age of vaccination may influence the level andduration of effectiveness.

High-risk groups including persons with HIV, persons
without a spleen, persons with chronic heart and / or lungdisease, and cigarette smokers are particularly vulnerable topneumococcal infections.
In the US, there are about 15 million visits to the doctor eachyear for ear infections (acute otitis media) alone. The cost ofthese visits is estimated at about $5 billion. As many as 55%of these visits may be for pneumococcal infections.
The Vaccines
In 1977, a first pneumococcal vaccine was licensed. The first
vaccine was a polysaccharide vaccine against 14 types ofpneumococci. It was replaced in 1983 with a polysaccharide
vaccine against 23 types (23-valent) (See Table 24). The
23-valent vaccine protected against > 85% of the strains thatcaused invasive pneumococcal disease in adults.

The impact of the vaccine

Efficacy from clinical trials for conjugate pneumococcal
vaccine has ranged from over 75% to over 95% against
invasive disease caused by the serotypes contained in thevaccine. Childhood pneumococcal vaccination has had analmost immediate impact on the burden of pneumococcal
disease (See Figure 81)150.
In addition, childhood conjugate pneumococcal immunization
programs have had a herd effect, impacting the incidenceof disease in unvaccinated age groups (See Figure82)151. By 2003, there were 30,000 fewer cases of invasive
pneumococcal disease in the US, including 20,000 fewer inchildren and adults who did not receive the vaccine152!

Pneumococcal serotypes contained in the 23-valent polysaccharide vaccine

But polysaccharide vaccines are typically insufficiently
immunogenic in infants and young children. To renderpolysaccharide vaccines immunogenic in this age group,a protein is coupled to the polysaccharide. This process isknown as protein conjugation.
A conjugate pneumococcal vaccine was first licensed in
2000. The first conjugate vaccine protected against the seventypes most frequently responsible for invasive pneumococcal
disease in US infants and young children (See Table 25). It
protected against about 90% of IPD in this age group.
In 2009, a 10-valent (decavalent) conjugate pneumococcal
vaccine was licensed. It contains types 1, 5, and 7F, in addition
to the types in the 7-valent vaccine. These three serotypes are
more prevalent in developing countries.

1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F,
20, 22F, 23F, 33F
TABLE 24. PNEUMOCOCCAL TYPES CONTAINED IN 23-VALENTPNEUMOCOCCAL POLYSACCHARIDE VACCINE

Pneumococcal serotypes contained in the 7-valent conjugate vaccine

4, 6B, 9V, 14, 18C, 19F, 23F

TABLE 25. PNEUMOCOCCAL TYPES CONTAINED IN 7-VALENTPNEUMOCOCCAL CONJUGATE VACCINE

Black S, Eskola J, Whitney C, et al. Pneumococcal conjugate and pneumococcal common protein vaccines. pp 531-567. In Vaccines 5th edition, S Plotkin, W
Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
150
Centers for Disease Control and Prevention. Pneumococcal disease and pneumococcal vaccines. May 2009.
www.cdc.gov/vaccines/pubs/pinkbook/downloads/Slides/Pneumo11.ppt
151
Simonsen L, Taylor RJ, Young-Xu Y, et al. Impact of pneumococcal conjugate vaccination of infants on pneumonia and influenza hospitalizations and mortality inall age groups in the United States. mBio 2011; 2(1):e00309-10.
149

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3 Public health effectiveness of vaccine implementation

A decline in antibiotic-resistant serotype invasive
pneumococcal infections has also been observed in the US.
Conjugate pneumococcal vaccination has reduced
incidence of vaccine-preventable serotypes by 99–100% asdemonstrated in post-licensure studies. Since the first
vaccine was licensed in 2000, most industrialized countries
have introduced conjugate pneumococcal vaccination for
infants where incidences have also declined remarkably. The
use of these vaccines in developing countries, where theburden of pneumococcal disease is very high, is expected tosave millions of lives.
The vaccine has been highly cost effective, costing about$7,800 / life-year saved in the US when accounting for a herd
effect. The herd effect and reduction of infectious pulmonary
disease in adults is even greater than the direct impact
on children.

	  FIGURE 81. DIRECT IMPACT OF CONJUGATE PNEUMOCOCCAL IMMUNIZATION ON INCIDENCE OF
PNEUMOCOCCAL DISEASE IN < 5 YEARS OF AGE	  FIGURE 82. IMPACT OF CHILDHOOD PNEUMOCOCCALVACCINE FACT BOOK 2012 | 91

3.8 Varicella Zoster virus (VZV)The Cause153

The Impact of the Disease

Varicella zoster virus (VZV)
causestwodiseases:varicella (chickenpox) andherpes zoster (shingles).
Varicella is a disease
resembling smallpox (SeeImage 18). It wasn’t until
1767 that varicella wasrecognized as distinct fromsmallpox. A century later,
Steiner proved that varicellawas infectious. In 1892,
Bokay suggested that there
Image 18. Typical pustular lesions
was a link between varicellaof varicella in a child.
SOURCE: CDC PUBLIC HEALTH IMAGE LIBRARY
and herpes zoster and that
HTTP://PHIL.CDC.GOV/PHIL/DETAILS.ASP
these were two different
diseases that result from the same virus154.

	  Varicella
Almost all humans are infected by the fourth decade of life, but
the incidence of the disease peaks in early childhood. Prior
to immunization in the US, the annual incidence of disease
was approximately 1,500 – 1,600 / 100,000 (See Table 26).
There were approximately 4 million cases of varicella annually
and about 11,000 to 13,500
hospitalizations in the US.
	
  Varicella is transmitted by the viruses contained in the skinlesions, or from the upper respiratory tract through air (SeeFigure 83). There is only one serotype of Varicella zoster virus
and the disease is exclusive to humans.

Varicella predisposes togroup A Streptococcus
infections and can lead topneumonia in the young.
Image 19. Herpes zoster showing
The case- fatality rate in thevesicular rash localized over theright chest.
US prior to immunization
SOURCE: FISLE HTTP://EN.WIKIPEDIA.ORG/WIKI/
approximated 2.6 deaths
FILE:HERPES_ZOSTER_CHEST.PNG
per 100,000 cases. But
fatality rates are 20 times
higher in adults and 50 times higher in developing countries.
In countries with high HIV sero-prevalence, fatality rates may
be higher.

A first infection results in varicella. The virus then remains
dormant in the body. When the body’s immune system isweakened, for any number of reasons, the virus can bereactivated and cause herpes zoster.

The major economic impact of the disease is from school
and workdays missed due to parents caring for sick children.
Hospitalization rates in industrialized countries may average
4.0 - 4.5 / 100,000 population.

Herpes zoster is a painful vesicular rash localized to a portionof the body such as around the waist (See Image 19).
Figure 83.
Transmissionof varicellazoster virus
from varicella isairborne from skinlesions or upper
respiratory tract.
SOURCE: E PALMER CDC
PUBLIC HEALTH IMAGE
LIBRARY HTTP://PHIL.CDC.
GOV/PHIL/DETAILS.ASP	  Country

Cases of varicella / 100,000 population

United Kingdom

240 - 880

Scotland480 - 790

France1,000 – 1,350

United States

1,500 – 1,600

TABLE 26. INCIDENCE OF VARICELLA IN SELECT COUNTRIES PRIOR TO
THE INTRODUCTION OF VARICELLA VACCINATION152

Centers for Disease Control and Prevention. What would happen if we stopped vaccinations? Pneumococcal.
http://www.cdc.gov/vaccines/vac-gen/whatifstop.htm#pneumo
153
Gershon AA, Takahashi M, Seward JF. Varicella vaccine. pp 915-958. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier,
China, 2008.
154
Gershon AA, Takahashi M, Seward JF. Varicella vaccine. pp 915-958. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier,
China, 2008.
152

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3 Public health effectiveness of vaccine implementation

Herpes zoster

The impact of the vaccine

Prior to immunization, by 40 years of age more than 99%of the population had been infected with varicella-zoster
virus. The at-risk population for herpes zoster was therefore
enormous. The annual incidence of herpes-zoster in the US,
in the general population, was 120 – 480 / 100,000, but 720-1,180 frequency / 100,000 for persons 60 years and older155.
This represented > 1 million cases / year.

Immunogenicity to varicellavaccine is excellent andvaccineefficacyfromclinical trials has been
evaluated at more than
90% from a single doseand over 98% after two
doses. Effectiveness trialsof vaccines post-licensure
confirm rates as high as
100% against moderate orsevere disease156.

The Vaccine
All strains of Varicella Zoster virus used to produce varicellavaccines are derived from the Oka strain of VZV. This strain
and a corresponding vaccine were originally developed byMichiaki Takahashi in Japan, at the University of Osaka.
The vaccine was first introduced in Japan, in 1988. It waslicensed in the US in 1995. It is available from several suppliersin a monovalent form, or in combination with Measles,
Mumps, Rubella vaccine. The quadrivalent vaccine (MMRV)
was licensed in the US in 2005.
A higher-dose VZV vaccine for the prevention of herpes zoster
was licensed in the US in 2006.
VZV vaccines are believed to impart long-lasting immunity (10– 20 years). They may result in mild rash and fever in about
5% of vaccine recipients.

Countries using childhood
varicella vaccine
Australia
CanadaGermany
Israel
Italy
Korea, South
Qatar
Uruguay
United States
TABLE 27. COUNTRIES THATHAVE UNIVERSAL CHILDHOOD
VARICELLA IMMUNIZATIONPROGRAMSThe US was the first
country to introduce a
universal childhood varicellaimmunization program, in
1995, but close to a dozen other countries now have similar
programs (See Table 27).
The US ACIP recommends a two-dose policy for varicellain children, similar to MMR vaccine. Since the introductionof varicella vaccine in the US, the incidence of varicellahas declined by as much as 90% and hospitalizations havebeen reduced by > 90% in children (See Figure 85)157. Direct
expenses for hospitalizations and care for varicella had
decreased by 74% by 2005.

FIGURE 84. IMPACT OF VARICELLA IMMNIZATION BY AGE IN TWO SURVEILLANCE CENTERS IN THE US.

Levin MJ. Zoster vaccine. pp 1057-1068. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
Gershon AA, Takahashi M, Seward JF. Varicella vaccine. pp 915-958. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier,
China, 2008.
157
Gershon AA, Takahashi M, Seward JF. Varicella vaccine. pp 915-958. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier,
China, 2008.
155
156

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3.9 Hepatitis B

The Cause158
Hepatitis B virus infects the liver and alters liver function. The
disease can be both acute and chronic. In acute disease,viral infection results in raised liver enzyme levels after about
60 days and causes jaundice about 90 days after infection.
The liver becomes large and painful and about 40% of
infections lead to hospitalization, in the US. About 0.5 – 1% of
infections may result in a fulminant form of disease (very rapid
progression) leading to liver failure. In the fulminant form, up
to 33% of cases result in death.

20. CT scan showing	  Imageenlargement of the liver as often
occurs in chronic hepatitis B
infections.
SOURCE: HTTP://UPLOAD.WIKIMEDIA.ORG/
WIKIPEDIA/COMMONS/F/FE/SE000.JPG

In chronic infections, there
is an initial period of viral
replication in the liver. Thisis followed by a period oflow (or no) viral replicationand no liver disease.
But hepatitis B surface
antigen (HBsAg) persist in
the blood for at least six
months. Chronic hepatitis
B increases the risk ofhepatocellular
carcinoma(cancer of the liver) andcirrhosis (See Image 20).

The virus spreads by transmission from mother to child atbirth, close contact, sexual contact and direct contact withmucosa, blood or body fluids (See Figure 85). In the US,
about 24,000 infants are born to Hepatitis B-infected mothers.
About 50% of new cases in the US are acquired by sexual
contact, and 15% from injection-drug use.

	
  Figure 85. Transmission of hepatitis
B virus is from body fluids andsexual contact
SOURCE: E PALMER CDC PUBLIC HEALTH IMAGESLIBRARY HTTP://PHIL.CDC.GOV/PHIL/DETAILS.

The risk of developing chronic infection is greatest when
acquired perinatally or in early childhood. At a young age
most infections are asymptomatic.
The Impact of the Disease
Globally, about 2 billion people have been infected, and 350
million are living with chronic hepatitis B infection. About
600,000 die each year from the consequences of chronic
hepatitis B infection (See Figure 86)159. 25% of adults withchronic hepatitis B who became infected during childhood
will die of liver cancer or liver cirrhosis.
600,000 deaths each year
from chronic hepatitis B
infections
350 million livingwith chronic
hepatitis B
infections

2 billion hepatatis B infections

FIGURE 86. GLOBAL IMPORTANCE OF HEPATITIS B

In the US, prior to hepatitis B immunization, about 200,000–
300,000 persons were infected each year. There are about
1.25 million chronic hepatitis B infections in the US, resulting
in 4,000–5,000 deaths each year160.
The prevalence of chronic infections is much higher in theseregions: East Asia, Southeast Asia, the Middle East, theAmazon basin, the Pacific Islands and Africa. In these regions,the lifetime risk of developing hepatitis B is > 60%. Before
immunization was introduced in East Asia and Southeast
Asia, as many as 30–50% of chronic infections in children
were the result of transmission from the mother to the childat birth.

Mast EE, Ward JW. Hepatitis B vaccine. pp 205-241. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
World Health Organization. Media center. Hepatitis B. Fact sheet n°204. August 2008. http://www.who.int/mediacentre/factsheets/fs204/en/index.html
160
Mast EE, Ward JW. Hepatitis B vaccine. pp 205-241. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
158
159

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3 Public health effectiveness of vaccine implementation

The Vaccine
The first hepatitis B vaccine developed and licensed in 1981
was produced from the plasma of persons chronically infectedwith hepatitis B. Hepatitis B surface antigen was filtered fromthe plasma and served as the vaccine antigen. In 1986 a
recombinant protein vaccine was licensed. The recombinantvaccine was manufactured from hepatitis B surface antigen
produced in yeast cells.
The vaccine is given in three or four doses in a primary series
by injection. More than 150 countries now recommend
hepatitis B vaccination. Hepatitis B vaccine is commonly
administered in combination with other childhood vaccines.

FIGURE 87. IMPACT OF ROUTINE INFANT HEPATITIS B IMMUNIZATION IN
THE US162

	  Serious adverse events are extremely rare, but local transient
mild reactions occur. Pain (3-29%) and fever (1-6%) are mostcommon reported.
The impact of the vaccine
Recombinant hepatitis B vaccines are 80-100% effectiveat preventing hepatitis B infections and 70-95% effective atpreventing perinatal infections if the first dose is given within
12 hours of birth161.
Everywhere they have been used, hepatitis B vaccines havesignificantly reduced the incidence of acute hepatitis B.
In the US, reports of acute hepatitis B have continued to
decline since the introduction of routine infant hepatitis B
vaccination in 1991. However, because many infections are
asymptomatic or go unreported, reports of acute hepatitis B
may underestimate the true number of new infections (SeeFigure 87).

FIGURE 88. EFFECTIVENESS OF HEPATITIS B VACCINES AT REDUCING
THE PREVALENCE OF CHRONIC HEPATITIS B INFECTIONS IN SELECTCOUNTRIES163	  In addition to reducing the incidence of acute hepatitis B
infections, routine infant hepatitis B immunization has also
been found to be effective at reducing the incidence ofchronic hepatitis B infections (See Figure 88).

Mast EE, Ward JW. Hepatitis B vaccine. pp 205-241. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
Centers for Disease Control and Prevention. Viral hepatitis statistics and surveillance. Disease burden from viral hepatitis A, B, and C in the United States.
http://www.cdc.gov/hepatitis/Statistics/index.htm
163
Mast EE, Ward JW. Hepatitis B vaccine. pp 205-241. In Vaccines 5th edition, S Plotkin, W Orenstein and P Offit, Eds, Saunders Elsevier, China, 2008.
161
162

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