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Advances in Vaccinology VOLUME 4 / ISSUE 4 / 2010 Rotavirus infection Professor Timo Vesikari: Rotavirus vaccine development Cervical Cancer Prophylactic HPV vaccination for young adult women Influenza The influenza A (H1N1) 2009 pandemic: the end of the first influenza pandemic of the 21 st century FIND MORE INSIDE GEN-2010-021
Transcript of 2010-AIV 4-Final
Advances in Vaccinology
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Rotavirus infectionProfessor Timo Vesikari: Rotavirus vaccine development
Cervical CancerProphylactic HPV vaccination for young adult women
Infl uenzaThe infl uenza A (H1N1) 2009 pandemic: the end of the fi rst infl uenza pandemic of the 21st centuryFI
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Immunization programs 4
Herd immunity: a critical factor to consider in
immunization
Rotavirus infection 8
Professor Timo Vesikari: Rotavirus vaccine development
News 12
Vaccine uptake is also affected by culture
Scientists have successfully cloned the human
cytomegalovirus offering new hope for the treatment of
potentially life-threatening diseases
Cervical Cancer 14
Prophylactic HPV vaccination for young adult women
Infl uenza 18
The infl uenza A (H1N1) 2009 pandemic: the end of the
fi rst infl uenza pandemic of the 21st century
Abstracts 22
High hepatitis A virus (HAV) vaccination coverage has
nearly eliminated transmission of HAV infection in
Alaska
Study revealed no increased risk of autism associated
with thimerosal-containing vaccines
Travel related diseases 24
Hajj pilgrims and vaccination requirements
Varicella 28
Varicella vaccines and traditional vaccination schedules
Misconceptions 32
Misconceptions about vaccinations
Congress Calendar 35
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3This journal is funded entirely by GlaxoSmithKline Biologicals, SA. All articles appearing in the journal have been written on behalf of or by GlaxoSmithKline Biologicals.
Editor-in-chiefProfessor David J. Weber, MD, MPH
Professor of Medicine, Pediatrics and Epidemiology
Schools of Medicine and Public Health
University of North Carolina
Associate Chief of Staff
University of North Carolina Health Care
Chapel Hill, NC
USA
International Editorial Board MembersAssociate Professor Lance C Jennings, QSO, FRCPath, PhD
Canterbury Health Laboratories &
Pathology Department, University of Otago
Christchurch
New Zealand
Professor Fred N. Were, MD, PhD
Department of Pediatrics and Child Health
University Of Nairobi
Kenyatta National Hospital
Kenya
Professor Fred Zepp, MD
Children’s Hospital
Johannes Gutenberg University
Mainz
Germany
Bernd Benninghoff, PhD
Dirk Poelaert, MD
Global Medical Affairs
GSK Biologicals
Rixensart
Belgium
ISSN 1784-1275
PublisherMed@Consulting BVBA
Zonneweeldelaan 25 b 19
3600 Genk
Belgium
E-mail: [email protected]
Herd immunity: a critical factor
to consider in immunization
Vaccines provide direct protection to vaccinated
individuals, but may also provide benefi ts to
unvaccinated individuals by reducing transmission of the
pathogen and thereby lowering the risk of infection.1
Herd immunity is the basis on which all national
immunization programs are designed. It is the concept
that not everybody in a population has to be immunized
to protect everyone in that population. As long as a
suffi cient number of children are immunized against
each disease for which there is a vaccine, protection
against that disease will be conferred to their wider
community.
5
Summary
Herd immunity can be defi ned as: "The reduction of infection or disease in the unimmunized segment as a result of immunizing a proportion of the population".Herd immunity is a collateral benefi t for all national immunization programs.
IMM
UN
IZAT
ION
PRO
GR
AM
SIn 1927, Kermack and McKendrick predicted that there
should exist a critical threshold level for the fraction
of susceptible individuals below which introduction
of infection can only lead to minor outbreaks.2 The
epidemiological theory proposed by Kermack and
McKendrick explains why it is possible to eradicate an
infectious agent without achieving complete vaccine
coverage.3-4
The herd immunity theory proposes that, in diseases
passed from person-to-person, it is more diffi cult to
maintain a chain of infection when large numbers of a
population are immune.
Figure 1. Herd immunity is defi ned as: "The reduction of infection or disease in the unimmunized segment as a result of immunizing a proportion of the population".
6
Herd immunity: a critical factor to consider in immunization
Herd immunity threshold
Although no vaccine offers 100% protection, the spread
of disease from person-to-person is much higher in
those who have not been vaccinated.5 Scientists have
found that when a certain percentage of a population
is vaccinated, the spread of the disease is effectively
stopped. This critical percentage of the population
that must be immunized, called the herd immunity
threshold, depends on three factors: the infectivity of
the disease, the vulnerability of the population, and
environmental factors (Table 1).6
Herd immunity has long been recognized as an
important benefi t of vaccines. Vaccines against
diphtheria poliovirus, varicella, rubella, measles,
hepatitis B virus and Bordetella pertussis have important
herd immunity effects.7 Largely unanticipated at the
time of vaccine introduction, the herd immunity effect
of the bacterial polysaccharide conjugate vaccines has
been a major contributor to the successful control of
invasive and noninvasive disease due to Haemophilus
DiseaseHerd immunity threshold (estimated)
Diphtheria 85%
Measles 83 – 94%
Mumps 75 – 86%
Pertussis 92 - 94%
Polio 80 - 86%
Rubella 80 – 85%
Smallpox 83 – 85%
Table 1. Estimated herd immunity thresholds for vaccine preventable diseases.7
infl uenzae type b (Hib), major serotypes of Streptococcus
pneumoniae, and Neisseria meningitidis serogroup C.8-9
Selective vaccination of schoolchildren against seasonal
infl uenza results in the indirect protection of other
age groups, such as adults and elderly, with reduced
incidence of the disease. Children play an important
role in the transmission of infl uenza within families,
schools and communities.10 In Russia, a mass vaccination
campaign in children 3 to 17 years of age signifi cantly
reduced infl uenza-like illness in children and in
unvaccinated elderly adults.11
Herd immunity and public perception of vaccination
Despite the fact that wide use of vaccination has
produced substantial achievements in the control of
vaccine-preventable diseases, some parents decide not
to immunize their children. As vaccination coverage
spreads through a community, it reaches a point at
which those who are unvaccinated are highly unlikely
to catch a disease because of the herd immunity effect.
Therefore, as a result of previous vaccination efforts the
incidence of a disease can be minimal. In this scenario
parents may choose not to vaccinate their child as they
do not understand the rationale for vaccinating against
a disease that poses a low risk of infection.
If enough parents decide not to have their children
vaccinated, more cases will start to appear and then the
entire population is at risk. To achieve herd immunity
it is important that health professionals and the public
are educated about the importance of continuing
immunization to prevent infection.12
On average, to achieve 100% protection against measles
in the United Kingdom the uptake of immunization
must be about 95%. A decade ago, health scares
7
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References1. John TJ, Samuel R. Herd immunity and herd effect: new insights and defi nitions. Eur. J. Epidemiol. 2000; 16 (7): 601-606. 2. Kermack WO, McKendrick AG. Contribution to the mathematical theory of epidemics—I. 1927. Bull. Math. Biol. 1991; 53: 33-55.3. Fine P. Herd immunity: History, theory, practice. Epidemiol Rev. 1993; 15: 265-302.4. Anderson RM, May RM. Infectious diseases of humans: Dynamics and control. Oxford: Oxford University Press (1991): 757 p.5. Jamison DT, Breman JG, Measham AR (editors). Chapter 4: Vaccine-preventable diseases. Priorities in Health: Disease Control Priorities Companion Volume.
World Bank Publications 2006. 6. Begg NT, Gay NJ. Theory of infectious disease transmission and herd immunity. In: Balows A, Sussman M, eds. Topley and Wilson's microbiology and micro-
bial infections. Vol 3. 9th ed. London: Edward Arnold, 1997.7. CDC. History and epidemiology of global smallpox eradication.
Available at: http://www.bt.cdc.gov/agent/smallpox/training/overview/pdf/eradicationhistory.pdf (Accessed on 15 September 2010).8. Makwana N, Riordan FA. Bacterial meningitis: the impact of vaccination. CNS Drugs 2007; 21 (5): 355-366.9. McVernon J, Ramsay ME, McLean AR. Understanding the impact of Hib conjugate vaccine on transmission, immunity and disease in the United Kingdom.
Epidemiol. Infect. 2008; 136 (6): 800-812.10. Glezen WP. Emerging infections: pandemic infl uenza. Epidemiol. Rev. 1996; 18: 64-76.11. Ghendon YZ, Kaira AN, Elshina GA. The effect of mass infl uenza immunization in children on the morbidity of the unvaccinated elderly. Epidemiol. Infect.
2006; 134: 71-78.12. Berger A. How does herd immunity work? BMJ 1999; 319: 1462-1467.13. Health Protection Agency Epidemiological Data – Measles, Mumps, Rubella.
Available at: http://www.hpa.org.uk/hpr/infections/immunisation.htm (Accessed on 15 September 2010).14. Jansen VA, Stollenwerk N, Jensen HJ, et al. Measles outbreaks in a population with declining vaccine uptake. Science 2003; 301: 804.
about the measles, mumps, and rubella vaccine (MMR
vaccine) contributed to a signifi cant drop of the MMR
immunization rates in the UK. The MMR coverage
dropped from 92% in 1995-1996 in England to 80%
in 2003-2004, a percentage below the herd immunity
threshold of measles.13 As a direct consequence,
outbreaks of measles and mumps occurred throughout
the UK.14
Professor Timo Vesikari:
Rotavirus vaccine development
References1. Parashar UD, Gibson CJ, Bresse JS, Glass RI. Rotavirus and severe childhood diarrhea. Emerg Infect Dis 2006;12 (2): 304-306.2. WHO. Detailed Review Paper on Rotavirus Vaccines. To be presented to the WHO Strategic Advisory Group of Experts (SAGE) on Immunization, April 2009.
Available at: http://www.who.int/immunization/sage/3_Detailed_Review_Paper_on_Rota_Vaccines_17_3_2009.pdf (Accessed August 30, 2009).3. Glass R, Parashar U, Bresee J, et al. Rotavirus vaccines: current prospects and future challenges. Lancet 2006; 368: 323-332.4. WHO. Report of the meeting on the future directions for rotavirus vaccine research in developing countries. Geneva; 2000. WHO/V and B/.00.23.5. Mrukowicz J, Szajewska H, Vesikari T. Options for the prevention of rotavirus disease other than vaccination. J Pediatr Gastroenterol Nut 2008; 46 Suppl 2:
S32-37.6. Dennehy PH. Rotavirus vaccines – an update. Vaccine 2007; 25: 3137-3141.7. CDC. Intussusception among recipients of rotavirus vaccine - United States, 1998-1999. MMRV 1999; 48: 577-581.8. Simonsen L, Viboud C, Elixhauser A, et al. More on RotaShield and intussusception: the role of age at the time of vaccination. J Infect Dis 2005; 192
(Suppl 1): S36-S43.9. Vesikari T. Rotavirus vaccines. Scand J Infect Dis 2008; 40: 691-695.
ROTA
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Rotavirus infection is the most common cause of
severe diarrheal disease in infants and young children
worldwide and continues to have a major global impact
on childhood morbidity and mortality.1
Rotavirus infects nearly every child before the age
of 3 years. The median age of a primary rotavirus
infection is younger in developing countries, ranging
from 6 to 9 months (80% occur among infants <1 year
old). Developing countries often exhibit one or more
periods of more intense rotavirus circulation against a
background of year-round rotavirus transmission and
a great diversity of rotavirus strains. In contrast, the
median age of primary infection is older in developed
countries, ranging from 9 to 15 months (65% occur
among infants <1 year old) caused by 4 to 5 common
rotavirus strains.2
Rotavirus is transmitted by the fecal-oral route and a
small infectious dose (< 100 virus particles) facilitates
spread from person to person or possibly via airborne
droplets. First infections in children 3 to 24 months of
age most often lead to vomiting, then watery diarrhea
that is sometimes accompanied by fever. In temperate
climates, rotavirus has a distinct peak in the cooler
winter months when it is the predominant pathogen
causing up to 70% of hospital admissions for diarrhea.4
Rotavirus vaccine development was identifi ed as a priority
During the past two decades, discussions among many
groups – including the World Health Organization
(WHO), the Institute of Medicine and the Global Alliance
for Vaccines and Immunization (GAVI) – have identifi ed
rotavirus vaccines as a priority for development.4 This
decision has been based primarily on the enormous
toll of rotavirus disease. It is estimated that each year
more than 500,000 children under fi ve years of age die
of rotavirus gastroenteritis, more than two million are
hospitalized and 25 million require an outpatient visit.1
In poor countries approximately one child in every 250
will die of rotavirus disease by fi ve years of age.
Control measures such as clean water initiatives and
improvements to personal hygiene have led to dramatic
declines in bacterial and parasitic gastroenteritis
infections across the world, but rates of rotavirus
infection and illness among children in industrialized
Figure 1. Professor Timo Vesikari (University of Tampere, Finland).
Professor Timo Vesikari: Rotavirus vaccine development
10
Figure 2. Rotavirus infects nearly every child before the age of 3 years.
and less-developed countries remain similar. Hygienic
measures are unlikely to lead to corresponding declines
in rotavirus burden.5
Longitudinal studies have demonstrated that naturally
acquired rotavirus infections provide protection against
rotavirus disease upon reinfection, and that protection is
greatest against the most severe disease outcomes.
Although children can be infected with rotavirus several
times during their lives, initial infection after age 3
months is most likely to cause severe diarrhea and
dehydration. A realistic goal for a rotavirus vaccine is to
duplicate the degree of protection against disease that
follows natural infection. Therefore, vaccine program
objectives include the prevention of moderate to severe
disease but not necessarily of mild disease associated
with rotavirus.6 Effective rotavirus vaccines are most
needed in developing countries where mortality
associated with rotavirus is high.
RotaShieldTM: the fi rst licensed rotavirus vaccine
The fi rst multivalent live oral reassortant vaccine
developed was RotaShieldTM (a rhesus rotavirus
tetravalent [RRV-TV] vaccine). This tetravalent vaccine
contained a mixture of four virus strains representing
the most commonly seen G types, G1 to G4. The
licensure of RotaShieldTM in the USA in 1998 was a truly
remarkable event, as it also marked the acceptance
of the concept of rotavirus vaccination in general.
Unfortunately, the vaccine had to be withdrawn
less than one year later, after about 100 cases of
intussusception had been reported in close temporal
proximity to the administration of RotaShieldTM.7 Most
cases were in infants to whom the fi rst dose of vaccine
had been given in the so-called catch-up program
between ages 3 and 9 months of age.8
The mechanism of this association has never been
elucidated, and the exact risk, which was judged to be
about one case of intussusception in 10,000 vaccine
recipients, remains controversial.
The risk of intussusception was evaluated in large
clinical trials for the currently available rotavirus vaccines
(RotarixTM and RotaTeqTM). In December 2008 The Global
Advisory Committee on Vaccine Safety (GACVS) reviewed
safety data from clinical trials with RotarixTM and
RotaTeqTM and surveillance data from the manufacturer
of RotaTeqTM. The GACVS concluded that these data
did not indicate an increased risk of intussusception
following vaccination compared to background rates.
An intussusception risk of the order of that which had
been associated with RotaShieldTM can be ruled out with
confi dence but further post-marketing surveillance with
RotarixTM and RotaTeqTM is necessary.
ROTA
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Two licensed oral rotavirus vaccines
The two live attenuated oral rotavirus vaccines
were licensed in 2006 for prevention of severe acute
gastroenteritis in children: RotarixTM (GSK), a human
rotavirus vaccine with G1P[8] serotype characteristics
and RotaTeqTM (Merck), a bovine-human reassortant
vaccine expressing human G 1- 4 and P[8] antigens.9
RotarixTM is a live vaccine containing the attenuated G1,
P[8] human rotavirus strain, and is recommended to be
orally administered in 2 doses beginning at 6 weeks of
age, with an interval of at least 4 weeks between the
fi rst and second dose, and with series completion by
24 weeks of age. RotaTeqTM is a live attenuated, bovine-
human reassortant rotavirus vaccine containing the
most common rotavirus antigens seen in humans
(G1, G2, G3, G4, and P[8]), and is recommended to be
orally administered in 3 doses, starting at 6 to 12 weeks
of age, with the subsequent doses administered at
4- to 10-week intervals, and the third dose
administered before 32 weeks of age. Both vaccines
have been demonstrated in clinical trials using
European, North American, and South American
populations to be 90 to 100% effective in preventing
severe rotavirus gastroenteritis and 74 to 85% effective
in preventing rotavirus infection of any severity. Clinical
trial data have shown both vaccines to have clinically
acceptable safety profi les.
Recent data from clinical trials with RotarixTM and
RotaTeqTM in developing countries (e.g. South Africa,
Malawi, Nicaragua, El Salvador) translated into
a lower effi cacy than in earlier trials in Europe and in
North and South America.
Vaccine safety continues to be clinically acceptable
in all settings studied. The public health impact of
rotavirus vaccine introduction may be greater in Africa
and Asia compared with other regions of the world due
to higher background rates of rotavirus disease and the
potential for higher numbers of prevented cases.2
Based on the results of these clinical trials the World
Health Organization (WHO) has recommended that
rotavirus vaccination should be included in all national
immunization programs.
The new recommendation by WHO's Strategic
Advisory Group of Experts (SAGE) extends an earlier
recommendation made in 2005 on vaccination in
the Americas and Europe, where clinical trials had
demonstrated clinically acceptable safety profi les and
effi cacy in populations with low and intermediate
mortality. New data from clinical trials, which
evaluated vaccine effi cacy in countries with high child
mortality, has led to the recommendation for global
use of the vaccine.
Although many programmatic and fi nancial challenges
face the global use of rotavirus vaccines, these vaccines
— and new candidates in the pipeline — hold promise
to make an immediate and measurable effect to
improve child health and survival from this common
burden affecting all children.
Post-marketing surveillance studies are needed to
monitor the vaccine impact on circulating viral strains
recovered from stools in order to test possible vaccine
selection pressure and potential strain replacement.
News ...
Figure 1. Hypothetical framework of vaccine uptake among older people.
13
NEW
S
Vaccine uptake is also affected by culture
According to a study published in the Journal of
Advanced Nursing, the cultural beliefs of the elderly
population infl uence their likelihood of choosing to be
vaccinated against infl uenza (Figure 1).
Infl uenza is a highly infectious viral disease that attacks
the human respiratory tract. Elderly people are especially
vulnerable to severe complications of infl uenza, which
may result in hospitalization and death.
Vaccination is the most effective measure to help
prevent the complications of infl uenza. However, vaccine
uptake rates for aging populations in many countries
still remain below the WHO recommended rate of 75%
to be achieved by the year 2010.
Researchers from Hong Kong explored the factors that
can infl uence the vaccine preferences of the elderly
and uptake of the infl uenza vaccine in nine countries
(South Korea, Canada, the United Kingdom, Greece,
Brazil, Turkey, China, Nigeria and Indonesia) with a
variety of cultures, economic status and vaccination
coverage. The researchers who developed a framework
for understanding vaccination behavior identifi ed fi ve
themes (Figure 1). Vaccine preferences were guided
by people’s “behavioral beliefs” in vaccination. There
are a number of factors considered, including the
perceived susceptibility to and severity of infl uenza,
vaccine effectiveness, vaccine cost, health-care and
social costs. Uptake of vaccination was likely to be more
concentrated in countries where the benefi t of vaccines
had become a “normative belief” in favor of vaccination.
The researchers said healthcare providers that help in
educating elderly people to understand the benefi ts of
vaccinations, as well as providing encouragement, will
be more successful in increasing vaccine uptake.
Enid Wai-yung Kwong, Samantha Mei-che Pang, Pin-pin Choi et al. Infl u-enza vaccine preference and uptake among older people in nine countries. Journal of Advanced Nursing 2010; 66 (10): 2297-2308.
Scientists have successfully cloned the human cytomegalovirus offering new hope for the treatment of potentially life-threatening diseases
Human cytomegalovirus (HCMV) is a clinically important
herpes virus that causes congenital malformations
worldwide. The development of new treatments against
HCMV has been hampered, as scientists have been
unable to stably replicate HCMV outside the human
body.
Dr Richard Stanton (School of Medicine, Cardiff
University, UK) and his team have successfully cloned
the HCMV: “HCMV has by far the largest genome of
all viruses affecting humans. Consequently it was
technically diffi cult to clone this virus in an intact form in
the laboratory. Cloning a copy of the virus has enabled us
to identify the genes causing the instability of the virus
outside the body. Following the identifi cation of these
genes, we have successfully developed cells in which we
can grow HCMV that corresponds to that which exists
in the human body. Cloning HCMV for the fi rst time will
help virologists develop antivirals and vaccines against
this virus.”
Dr Richard Stanton added: “HCMV has been designated
as the highest priority vaccine target by the US Institute
of Medicine. When developing vaccines or anti-viral
agents, it is crucial to work with a virus that accurately
represents the virus present in patients. For the fi rst
time our work has enabled us to create an exact copy of
HCMV outside of the body offering a vital step forward
in the developments of new treatments.”
Richard J. Stanton, Katarina Baluchova, Derrick J. Dargan, et al. Reconstruc-tion of the complete human cytomegalovirus genome in a BAC reveals RL13 to be a potent inhibitor of replication. Journal of Clinical Investigation 2010; 120 (9): 3191-3208.
Probability calculation Utility calculation
Behavioral beliefs Preferencefor vaccination
Vaccinationuptake
Normative beliefsin vaccination Cues to action
AvailabilityAccessibilityAffordability
Cultural values, health beliefs
Indigenous health practices
Susceptibility to andseverity of infl uenza
Vaccineeffectiveness
Vaccinecost
Healthcarecost
Socialcost
(reprinted with permission)
Prophylactic HPV vaccination for
young adult women
References1. National Cancer Institute. Understanding cancer series: HPV vaccine [Online] Available from:http://www.cancer.gov/cancertopics/understandingcancer/HPV-vaccine/allpages [Accessed date: January 2010]2. World Health Organization. Expert Committee on Biological Standardization. Guidelines to assure the quality, safety and effi cacy of recombinant Human
Papillomavirus viruslike particle vaccines, accessed on 27/3/2009 at http://screening.iarc.fr/doc/WHO_vaccine_guidelines_2006.pdf3. Muñoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classifi cation of human papillomavirus types associated with cervical cancer. N Engl J Med 2003;
348: 518-527.4. Bosch X, Burchell A, Schiffmann M et al. Epidemiology and Natural History of Human Papillomavirus Infections and Type-Specifi c Implications in Cervical
Neoplasia. Vaccine 26S (2008) K1–K165. de Sanjose S, Quint W, Alemany L, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide
study. Lancet Oncol. 2010; 11: 1048-1056.6. Stanley M.Immune responses to human papillomavirus. Vaccine 2006,Vol24S1/16-227. Viscidi RP, Schiffman M, Hildesheim A, et al. Seroreactivity to human papillomavirus (HPV) types 16,18 or 31 and risk of subsequent HPV infection: results
from a population-based study in Costa Rica. Cancer Epidemiol. Biomarkers Prev. 2004; 13: 324-327.8. Mayrand M, Coutlée F, Hankins C, et al. Detection of human papillomavirus type 16 DNA in consecutive genital samples does not always represent persist-
ent infection as determined by molecular variant analysis. J. Clin. Microbiol. 2000; 38 (9): 3388-3393.9. Safaei A, Khanlari M, Momtahen M, et al. Prevalence of high-risk human papillomavirus types 16 and 18 in healthy women with cytologically negative
pap smear in Iran. Indian J. Pathol. Microbiol. 2010; 53 (4): 681-685.10. Ferlay J, Bray F, Pisani P, Parkin DM. Globocan 2002: Cancer incidence, mortality and prevalence worldwide. IARC Cancerbase No. 5. Version 2.0, IARCPress,
Lyon, 2004.Available at: www.depdb.iarc.fr/globocan/GLOBOframe.htm11. World Health Organization. Initiative for Vaccine Research. http://www.who.int/vaccine_research/diseases/hpv/en/ Accessed on October 8, 2010.12. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55: 74-108.13. Gravitt PE, Jamshidi R. Diagnosis and management of oncogenic cervical human papillomavirus infection. Infect. Dis. Clin. North Am. 2005; 19: 439-458.14. Brown DR, Shew ML, Qadadri B, et al. A longitudinal study of genital human papillomavirus infection in a cohort of closely followed adolescent women. J.
Infect. Dis. 2005; 191: 182-192.15. Bosch FX, de Sanjose S. Chapter 1: Human papillomavirus and cervical cancer--burden and assessment of causality. J. Natl. Cancer Inst. Monogr. 2003; 3-13.16. Wright TC, Van Damme P, Schmitt HJ, et al. Chapter 14 : HPV vaccine introduction in industrialized countries. Vaccine 2006; 24 Suppl 3: S122-S131.17. Castle PE, Schiffman M, Herrero R, et al. A prospective study of age trends in cervical human papillomavirus acquisition and persistence in
Guanacaste,Costa Rica. J. Infect. Dis. 2005; 191: 1808-1816.18. Muñoz N, Méndez F, Posso H, et al. Incidence, duration, and determinants of cervical human papillomavirus infection in a cohort of Colombian women-
with normal cytological results. J. Infect. Dis. 2004; 190 (12): 2077-2087.19. Szarewski A. 9th International Multidisciplinary Congress of the European Research Organisation on Genital Infection and Neoplasia. Monte
Carlo,Monaco, February 17-20 2010. Abstract.20. Huh W, Paavonen J, Naud P, et al. Effi cacy of the HPV-16/18 AS04-adjuvanted vaccine in women according to their initial DNA and serostatus: Patricia end-of-
study results. 13th Biennial Meeting of the International Gynaecologic Cancer Society 2010. Prague, Czech Republic, October 23-26, 2010. Abstract 1782.21. Olsson S, Kjaer S, Sigurdsson K, et al. Evaluation of quadrivalent HPV 6/11/16/18 vaccine effi cacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection. Human Vaccines 2010; 5 (10): 696-704.
Figure 1. Persistence of the oncogenic human papillomavirus (HPV) by age group.17
15
Summary
Prophylatic cervical cancer vaccines have the potential to help prevent cervical cancer caused by certain oncogenic human papillomavirus (HPV) types. These vaccines help protect against: incident and persistent infections, cytological abnormalities, cervical intraepithelial neoplasia (CIN) and pre-cancerous lesions (CIN 2, CIN 3 and adenocarcinoma in situ). The primary target population for HPV vaccination to date is the non-sexually active, pre-adolescent girls. However, latest data of a large clinical trial shows that sexually active girls/women between 15 and 26 years also benefi t from HPV vaccination.
CER
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What is cervical cancer?
Cervical cancer is almost exclusively caused by a
virus called human papillomavirus (HPV) which is
transmitted through sexual activity including intimate
skin contact.1 There are about 100 known types of
HPV2, of which at least 15 can cause cervical cancer.3
HPV types 16 and 18 are the most common cancer
causing virus types and are found in for over 70 percent
of all cervical cancer cases worldwide.4 Globally, HPV
types 16, 18, 31, 33, 35, 45, 52, and 58 are the eight
most frequent cancer-causing HPV types, which are
responsible for about 91% of all cervical cancer.5
HPV is a particularly challenging virus as it is able to
evade detection by the body’s natural immune system.
As a purely mucosal virus which does not enter the
bloodstream and does not kill the cells it infects, HPV
avoids sending out the usual signals that trigger the
immune system.6 Thus, the natural immune response
following infection appears not to be strong enough
to protect against initial or subsequent infection with
only a small number of subjects experiencing some
partial protection.6, 7, 8, 9
The global burden of cervical cancer
Worldwide, cervical cancer kills on average one woman
in the world every two minutes10 and is the second
biggest cause of female cancer mortality.11 Globally,
cervical cancer is estimated to affect 510,000 women
each year.11 In addition, women who survive cervical
cancer sometimes are left infertile by radical surgery to
remove the cancerous tissue.
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40
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20
10
0
Pers
iste
nce
(%)
Age group (years)
<25 25-34 35-44 45-54 55-64 ≥65
Figure 2. Vaccine effi cacy (%)(*) against CIN2+ associated with HPV 16/18 in women aged 15 to 25 years, with or without evidence of previous exposure. 20
(*) Vaccine effi cacy reported in total vaccinated cohort = women receiving > 1 dose with Type Assignment Algorithm: assigns probable HPV causality in lesions with multiple HPV types.
16
The risk of infection
Every sexually active woman is at risk of oncogenic
HPV infection.12,13 It is estimated that up to 50-80 % of
women will acquire an HPV infection in their lifetime,
and up to 50 % of those infections will be with an
oncogenic HPV type.14,15
Although the peak of HPV infection occurs in women
aged less than 25 years old, incident and prevalent
infection can continue throughout adult life due to
subsequent infection by oncogenic types.16 There is
evidence that infections among older women (over 35)
are more likely to be persistent than those in younger
women, and therefore older women may be at increased
risk for development of cervical cancer (Figure 1).17
In a cohort trial 1,610 HPV-negative women (15–85
years) – with normal cytological results at baseline
– were monitored every 6 months for an average of
4.1 years. 18 The oncogenic HPV incidence was 5/100
woman-years. The 5-year cumulative risk of acquiring
any HPV infection remained at 30% in women 25 to
29 years old and 22% in women 30 to 44 years old. The
cumulative risk of HPV infection declined to 12% in
women > 45 years old. A small increase in the incidence
of oncogenic HPV infection was also seen in this cohort
after the age of approximately 40, peaking at around
age 50. These results confi rm that a signifi cant risk
of newly acquired HPV infections remains in sexually
active women of all ages.
Prophylactic HPV vaccination for young adult women
100
80
60
40
20
0
Pers
iste
nce
(%)
Seronegativefor HPV 16/18
IrrespectiveHPV 16/18 serostatus
Seropositive for HPV 16 and/or 18
98.5%(95% CI, 94.3-99.8)
81.1%(95% CI, 13.2-98.0)
97.2%(95% CI, 92.7-99.3)
CER
VIC
AL
CA
NC
ER
17
The use of HPV vaccinations should be in accordance
with offi cial recommendations and the approved
product information in your country.
Preventing cervical cancer through vaccination
Current HPV vaccines do not have a therapeutic effect
and do not prevent the development of CIN in women
already infected with a given HPV type prior to vaccine
administration. It is not a surprise that from a public
health perspective, the primary target population for
HPV vaccination is non-sexually active, pre-adolescent
girls. The girls in this population generally have not
been exposed to any of the vaccine-targeted HPV types.
New data has shown, however, that the majority of
young adult women potentially could benefi t from
vaccination. The AS04- adjuvanted HPV-16/18 vaccine
against HPV was shown to be highly effi cacious
against pre-cancerous lesions (CIN 2+) associated with
HPV16/18 in women aged 15- 25 years with evidence
of a previous infection (seropositive for HPV-16 and/
or -18).19-20 The study has shown that women aged 15
-25 years currently infected (DNA positive) with one
vaccine HPV type were protected against the other
vaccine type, if DNA negative for that type (Figure 2).20
Similar results were obtained with the quadrivalent
HPV vaccine (HPV types 6/11/16/18) in subjects with
serological evidence of prior vaccine type
HPV infection.21
Conclusion
The priority of routine vaccination programs with
HPV vaccines should be the primary target population
of pre-adolescent girls and young women; however,
new data in women aged 15 to 25 years with the
AS04- adjuvanted HPV-16/18 vaccine has shown
effi cacy against CIN2+ associated with HPV-16/18
even in women with evidence of a previous infection
(seropositive). 19-20
The infl uenza A (H1N1) 2009 pandemic: the end of the fi rst infl uenza pandemic of the 21st century
19
INFL
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Virology
Instead of the H5N1 avian infl uenza virus, a swine-origin
H1N1 infl uenza virus was responsible for the start of the
infl uenza A (H1N1) 2009 pandemic. This virus contained
a combination of gene segments that had previously
not been reported in swine or human infl uenza viruses.3
Its genome is the result of a reassortment and contains
genes from triple-reassortant North American swine virus
and Eurasian swine virus lineages. No expert expected
the emergence of this pandemic H1N1 virus (Figure 1). The
majority of pandemic infl uenza A (H1N1) 2009 viruses
analyzed to date are antigenically and genetically
closely related to the recommended vaccine virus
A/California/7/2009.4
As a consequence of increasing concern following the
Hong Kong H5N1 outbreak in 1997, and subsequent
events with associated human infections, pandemic
preparedness planning has been a focus of WHO’s
global infl uenza strategy. During a briefi ng on 29 April
2009 Margaret Chan, the Director-General of the WHO,
stated: “The world is better prepared for an infl uenza
pandemic than at any time in history. Preparedness
measures undertaken because of the threat from H5N1
avian infl uenza were an investment and we are now
Summary
On 11 June 2009 the World Health Organization (WHO) declared the start of the fi rst infl uenza pandemic of the 21st century.1 More than one year later, on 10 August 2010 Margaret Chan, the Director-General of the WHO, announced that the world has moved into the post-pandemic period.2 How might we prepare for a future infl uenza pandemic? The lessons that have been learned during the fi rst infl uenza pandemic of this century could help in answering this important question.
Figure 1. Gene segment composition of the pandemic infl uenza A (H1N1) 2009 virus.6
1. HA Classic swine, North American lineage
2. NA Eurasian swine lineage
3. PA Avian, North American lineage
4. PB1 Human seasonal H3N2
5. PB2 Avian, North American lineage
6. NP Classic swine, North American lineage
7. M Eurasian swine lineage
8. NS Classic swine, North American lineage
20
benefi ting from this investment. For the fi rst time in
history, we can track the evolution of a pandemic in real
time.”5
Epidemiology
Contrary to what had been expected, North America,
and not South East Asia, was the epicenter of the fi rst
infl uenza pandemic of the 21st century. The novel H1N1
virus was fi rst detected in a widespread outbreak in
Mexico in March-April 2009.7 Within weeks, the virus
that was causing the epidemic in Mexico was identifi ed
in many other countries worldwide. On 11 June 2009, the
WHO raised the phase of pandemic alert to level 6.
The pandemic infl uenza A (H1N1) 2009 virus has been
shown to affect all age groups.
Rapid spread has been observed in some communities,
especially in crowded places such as schools. In school
outbreaks in the UK, around 30% to 50% of students have
been infected.8 A proportion of older adults may have
had a degree of cross protection conferred by pre-existing
neutralising antibodies directed against other infl uenza A
viruses.9
In certain disadvantaged groups, including indigenous
populations of North America and the Australasia-Pacifi c
region, rates of severe A (H1N1) 2009 infl uenza virus
infection have been increased.10
To date, the epidemiology of pandemic A (H1N1) 2009
virus infection indicates that children and young adults
have had the highest attack rates.11 The risk factors for
severe disease from pandemic A (H1N1) 2009 virus
infection reported are considered not disimilar to those
risk factors identifi ed for complications from seasonal
infl uenza (Table 1).11 Pregnant women, especially those
with co-morbidities, are at increased risk for complications
from infl uenza virus infection. Infl uenza in pregnancy is
associated with an increased risk of adverse pregnancy
outcomes, such as spontaneous abortion, preterm birth,
and fetal distress.11
Table 1. Groups at increased risk of severe disease
from pandemic H1N1/09 virus infection.11
1. Infants and young children, in particular below
2 years;
2. Pregnant women;
3. Persons of any age with chronic pulmonary
disease (e.g., asthma, COPD);
4. Persons of any age with chronic cardiac disease
(e.g., congestive cardiac failure);
5. Persons with metabolic disorders
(e.g., diabetes);
6. Persons with chronic renal or hepatic
disease, certain neurological conditions,
haemoglobinopathies, or primary or secondary
immunosuppressive conditions;
7. Children receiving chronic aspirin therapy;
8. Persons above 65 years.
The infl uenza A (H1N1) 2009 pandemic: the end of the fi rst infl uenza pandemic of the 21st century
Clinical features
Most people with pandemic infl uenza A(H1N1) 2009 virus
infection have had self-limiting uncomplicated illness.
Symptoms were generally mild and closely resembled
seasonal infl uenza. The most commonly reported
symptoms included cough, fever, sore throat, muscle
21
INFL
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strongly suspected infl uenza virus infection.11
Inactivated- and live attenuated monovalent vaccines
containing the recommended vaccine virus strain
A/California/7/2009 (H1N1) have been approved by
the FDA, European Medicines Agency (EMA) and other
regulatory bodies.13-14 Many countries reported good
vaccination coverage, especially in high-risk groups,
and this coverage further increases community-wide
immunity.15
Evidence from an observational study to assess the
effectiveness of the pandemic infl uenza A (H1N1) 2009
vaccine demonstrated a high degree of protection in the
vaccinated high-risk populations (e.g. pregnant women,
children, health-care workers, patients with at-risk co-
morbidities) against the infl uenza strain.16
aches, malaise, and headache. Some patients reported
gastrointestinal symptoms (nausea, vomiting, and/or
diarrhea).6
However, for some severe complications occurred such
as pneumonia resulting in respiratory failure, acute
respiratory distress syndrome (ARDS), multi-organ failure
and death.12
Treatment and vaccination
Pandemic infl uenza A (H1N1) 2009 virus is currently
susceptible to the neuraminidase inhibitors oseltamivir
and zanamivir, but resistant to the M2 inhibitors
amantadine or rimantadine. Antiviral therapy was
recommended by the WHO to patients considered to be
at higher risk of developing severe or complicated illness
and who had complicated illness due to confi rmed or
References1. World Health Organization. Transcript of statement by Margaret Chan, Director-General of the World Health Organization, 11 June 2009.
Available at: http://www.who.int/mediacentre/infl uenzaAH1N1_presstranscript_20090611.pdf. (Accessed on 15 September 2010).2. World Health Organization. Transcript of statement by Margaret Chan, Director-General of the World Health Organization, 10 August 2010.
Available at: http://www.who.int/mediacentre/vpc_transcript_joint_2010_08_10.pdf. (Accessed on 15 September 2010).3. Garten RJ, Davis CT, Russell CA, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) infl uenza viruses circulating in humans. Science
2009; 325: 197-201. 4. World Health Organization. Weekly virological update on 12 August 2010.
Available at: http://www.who.int/csr/disease/swinefl u/laboratory13_08_2010/en/index.html (Accessed on 15 September 2010).5. World Health Organization. Transcript of statement by Margaret Chan, Director-General of the World Health Organization, 29 April 2009.
Available at: http://www.who.int/mediacentre/news/statements/2009/h1n1_20090429/en/index.html (Accessed on 15 September 2010).6. Trifonov V, Khiabanian H, Rabadan R. Geographic dependence, surveillance, and origins of the 2009 infl uenza A (H1N1) virus. N. Engl. J. Med. 2009; 361:
115-119.7. López-Cervantes M, Venado A, Moreno A, et al. On the spread of the novel infl uenza A (H1N1) virus in Mexico. J. Infect. Dev. Ctries 2009; 3 (5): 327-330.8. Mathematical modelling of the pandemic H1N1 2009. Wkly Epidemiol. Rec. 2009; 84: 341-348.9. Hancock K, Veguilla V, Lu X, et al. Cross-reactive antibody responses to the 2009 pandemic H1N1 infl uenza virus. N. Engl. J. Med. 2009; 361: 1945-1952.10. Louie JK, Acosta M, Winter K, et al. Factors associated with death or hospitalization due to pandemic 2009 infl uenza A(H1N1) infection in California. JAMA
2009; 302: 1896-1902.11. World Health Organization. Clinical management of human infection with pandemic (H1N1) 2009: revised guidance. http://www.who. int / csr / re-
sources / publications / swinefl u / clinical_management_h1n1.pdf.12. Health Protection Agency. Pandemic H1N1 2009 clinical practice note—managing critically ill cases (28 July 2009).
Available at: http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1248854036293 (Accessed on 15 September 2010).13. Centers for Disease Control and Prevention. Update on infl uenza A (H1N1) 2009 monovalent vaccines. MMWR 2009; 58:1100-1101.
Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5839a3.htm. (Accessed on 15 September 2010).14. European Medicines Agency. Pandemic infl uenza (H1N1) website.
Available at: http://www.emea.europa.eu/infl uenza/vaccines/home.htm. (Accessed on 15 September 2010).15. World Health Organization. Director-General's opening statement at virtual press conference. 10 August 2010.
Available at: http://www.who.int/mediacentre/news/statements/2010/h1n1_vpc_20100810/en/index.html (Accessed on 15 September 2010).16. Simpson CR, Ritchie LD, Robertson C, et al. Vaccine effectiveness in pandemic infl uenza - primary care reporting (VIPER): an observational study to assess
the effectiveness of the pandemic infl uenza A (H1N1)v vaccine. Health Technol. Assess. 2010; 14 (34): 313-346
Abstracts
23
AB
STR
AC
TS
High Hepatitis A Virus (HAV) vaccination coverage has nearly eliminated transmission of HAV infection in Alaska
Hepatitis A is a highly contagious liver infection. It
is one of the several types of hepatitis viruses that
cause infl ammation, affecting the liver's functionality.
Alaska has previously experienced cyclic hepatitis A
epidemics, and the rate among Alaska Native people was
signifi cantly higher than among other racial and ethnic
groups.
Hepatitis A vaccines were licensed in the US in 1995
and recommended by the Advisory Committee on
Immunization Practice (ACIP) for routine vaccination of
US children in populations with high rates of hepatitis
A virus (HAV). Populations include those found in
American Indian and Alaska Native communities
throughout the United States.
Rosalyn Singleton et al. evaluated the impact of
universal childhood vaccination, initiated in 1996, on
HAV epidemiology in Alaska by analyzing HAV cases
reported to the State of Alaska. HAV incidence in all age
groups declined 98.6% from 60.0/100,000 in 1972–1995
to 0.9/100,000 in 2002–2007. The largest decrease
(99.9%) was in Alaska Native people, whose incidence
(0.3%) in 2002–2007 was lower than the overall US
2007 rate (1.0%) (Figure 1). The decrease (99.8%) among
children aged 0 to14 years was the largest. Routine
childhood vaccination has nearly eliminated HAV
infection in Alaska.
Rosalyn J. Singleton, Sarah Hess, Lisa R. Bulkow, et al. Impact of statewide childhood vaccination program in controlling hepatitis A virus infection in Alaska. Vaccine 2010; 28: 6298-6304.
Study revealed no increased risk of autism associated with thimerosal-containing vaccines
From the 1930s to the early 2000s, many routinely
administered childhood vaccines contained very tiny
amounts of thimerosal as preservative. Thimerosal is an
organic mercury containing compound having 49.55 per
cent mercury by weight, and is initially metabolized to
ethylmercury and thiosalicylate.
Ethylmercury exposure from the preservative thimerosal
had been hypothethized as a possible risk factor for
autism or other ASD’s (autism spectrum disorders).
In 1999, as a precautionary measure, the American
Academy of Pediatrics and the US Public Health Service
published a joint statement which included a request
that manufacturers eliminate or reduce as expeditiously
as possible the mercury content in their vaccines.
Many vaccines recommended for children ≤ 6 yr of age
subsequently were made available in thimerosal-free or
thimerosal-reduced formulations.
Most previous research has not revealed an increased
risk of autism associated with thimerosal-containing
vaccines (http://www.cdc.gov/vaccinesafety/concerns/
thimerosal/index.html). In a recent study, US researchers
conducted a case-control study in 3 managed care
organizations of 256 children with ASD and 752
controls. This new study revealed no increased risk of
ASD associated with receipt of thimerosal-containing
vaccines. No increased risk was found for subtypes
of ASD, including ASD with regression, and prenatal
exposure was also not associated with a risk of ASD.
Cristofer S. Price, William W. Thompson, Barbara Goodson, et al. Prenatal and infant exposure to thimerosal from vaccines and immunoglobulins and risk of autism. Pediatrics 2010; published online Sep 13, 2010.
Year
2000
1800
1600
1400
1200
1000
800
600
400
200
0
Rate
per
100
,000
1972 1975 1978 1981 1984 1987 1990 1993 1996 1999 2002 2005
10
9
8
7
6
5
4
3
2
1
0
Rate
per
100
,000
Year
96 97 98 99 00 01 02 03 04 05 06 07
Figure 1. Hepatitis A virus infection rate per 100,000 by year, 1972–2007, among Alaska Native and non-Native Alaska persons.
Native
Non-native
(reprinted with permission)
Hajj pilgrims and
vaccination requirements
References1. Memish ZA. The Hajj: communicable and non-communicable health hazards and current guidance for pelgrims. Euro Surveill. 2010; 15 (39): 19671.2. Memish ZA, et al. Establishment of public health security in Saoudi Arabia for the 2009 Hajj in response to pandemic infl uenza A H1N1. Lancet 2009; 374:
1786-1791.3. Shek LP, Lee BW. Epidemiology and seasonality of respiratory tract virus infections in the tropics. Paediatr. Respir. Rev. 2003; 4 (2): 105-111.4. El Bashir H, Haworth E, Zambon M, et al. Infl uenza among U.K. pilgrims to hajj, 2003. Emerg. Infect. Dis. 2004; 10 (10): 1882-1883.5. International consultation on infectious disease prevention and control for Umra and the Hajj: Technical meeting report, Jeddah, Kingdom of Saudi Arabia,
5-7 Rajab 1430H/28-30 June 2009. Available at: http://www.emro.who.int/csr/h1n1/pdf/infectiousdiseases_hajj_umra.pdf (Accessed on 15 September 2010).
6. World Health Organization. Health conditions for travellers to Saudi Arabia for the pilgrimage to Mecca (Hajj). Wkly Epidemiol. Rec. 2009; 46 (84): 477-484.
7. Al-Mazrou YY, Al-Jeffri MH, Abdalla MN, et al. Changes in epidemiological pattern of Meningococcal disease in Saudi Arabia; Does it constitute a new chal-lenge for prevention and control? Saudi Med. J. 2004; 25: 1410-1413.
8. World Health Organization. Health conditions for travellers to Saudi Arabia for the pilgrimage to Mecca (Hajj). Wkly Epidemiol. Rec. 2006; 81 (44): 422-4239. Gatrad AR, Sheikh A. Hajj and risk of blood borne infections. Arch. Dis. Child. 2001; 84: 375 10. Memish ZA, Venkatesh S, Ahmed QA. Travel epidemiology: the Saudi perspective. Int J Antimicrob Agents 2003; 2: 96-101. 11. Memish ZA. Health conditions for travelers to Saudi Arabia for (Hajj) for the year 1431H/2010. J. Infect. Publ. Health 2010; 3: 92-94.
25
TRA
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DIS
EASE
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Summary
The Hajj pilgrimage in Mecca (Saudi Arabia) is currently the largest annual congregation in the world. Extended close contact, shared accommodation and overcrowding are all associated with an increased risk of infection. Possible outbreaks of disease at the Hajj include respiratory tract infections including infl uenza and pneumococcal pneumonia, invasive meningococcal disease, blood-borne diseases, and skin infections.
The Hajj is the annual pilgrimage to Mecca, Saudi
Arabia and is currently one of the largest annual mass
gatherings. The Hajj is one of the fi ve pillars of Islam. It is
a religious duty that must be carried out at least once in
their lifetime by every Muslim who can afford to do so.
In 2009, over 2.5 million pilgrims visited Mecca and the
vast majority being international travellers. The pilgrims
usually arrive two months before the Hajj takes place.
Camps consisting of fl ats and tents are provided by
the Ministry of Hajj.1 The Hajj takes place between the
8th and 13th day of the last month of the Islamic lunar
calendar and therefore Hajj falls 10 to 11 days earlier
each year.
In 2010, the dates for the Hajj fell between the 14 to the
18 November. During this period, extreme congestion of
this geographically diverse population amplifi es health
risks, particularly infectious diseases.1
Figure 1. The Kaaba is a cube-shaped building in Mecca and it is the most sacred site in Islam. During the Hajj, pilgrims walk around the Kaaba seven times in a counter-clockwise direction.
26
Hajj pilgrims and vaccination requirements
Vaccination requirements
While pilgrimage to Mecca was the context for severe
cholera outbreaks in the 19th century, the health
situation for pilgrims has greatly improved.2 The
Ministry of Health (MoH) of Saudi Arabia takes the
health security very seriously and each year gives
appropriate immunization requirements and advice.
Infl uenza
As Saudi Arabia is in the tropical sphere, infl uenza is
expected to occur in two different peaks corresponding
to the winter seasons of northern and southern
hemispheres.3
The attack rate of infl uenza during the Hajj is reported
to be as high as 38% despite vaccination.4 Before the
start of the infl uenza A (H1N1) 2009 pandemic the
Ministry of Health of Saudi Arabia recommended
that pilgrims – particularly those with pre-existing
conditions (e.g. elderly, patients with chronic heart
disease or with cardiac, hepatic or renal failure) – be
vaccinated against infl uenza before arrival.
The infl uenza A (H1N1) 2009 pandemic imposed extra
concerns regarding public health during Hajj 2009.
The Ministry of Health of Saudi Arabia organized
together with the World Health Organization (WHO)
a consultation process to develop recommendations
to mitigate the effects of the infl uenza pandemic
during the 2009 Hajj.5 Special entry visa requirements
and recommendations for the Hajj were issued by
the Ministry of Health of Saudi Arabia. During the
pandemic, people at high risk were advised to postpone
their participation in the Hajj. Additionally, it was
advised that all pilgrims be vaccinated against seasonal
and pandemic infl uenza.6
Meningococcal meningitis
Until the year 2000, bivalent (serogroups A, C)
meningococcal vaccination was recommended for all
pilgrims to the Hajj areas. During the Hajj pilgrimages
of 2000 and 2001, there was an epidemiological
shift from serogroup A disease to serogroup W135
disease together with an increase in incidence in
younger age groups.7 As a result, the quadrivalent
(ACWY135) meningococcal polysaccharide vaccine
was introduced in 2001 by the Ministry of Health
for all pilgrims. All Hajj pilgrims are required to
submit proof of vaccination with the quadrivalent
(ACWY 135) meningococcal vaccine as part of the
Hajj visa application.Vaccination with quadrivalent
polysaccharide vaccines has proved successful and has
quelled meningococcal disease since 2002.
Polio
Although poliomyelitis is close to eradication, all
pilgrims are advised to ensure their poliomyelitis
vaccination is up to date. If the last dose of
poliomyelitis vaccine was more than 10 years ago
a booster with trivalent tetanus, diphtheria and
poliomyelitis vaccine should be given.
The Ministry of Health of Saudi Arabia recommends
that all people aged less than 15 years travelling to
Saudi Arabia from polio-affected countries show proof
of vaccination with oral poliomyelitis vaccine 6 weeks
prior to application for their entry visa.1 Irrespective
of previous immunization history, children aged less
than 15 years arriving in Saudi Arabia will also receive
one oral poliomyelitis vaccine dose at border points
on arrival in Saudi Arabia.8 All pilgrims regardless of
age and vaccination status coming from Afghanistan,
India, Nigeria and Pakistan – the countries that never
27
TRA
VEL
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ATED
DIS
EASE
S
completely interrupted the transmission of the polio virus
– should receive one dose of oral poliomyelitis vaccine.1
Hepatitis B
As part of the rites of Hajj, men shave their heads
although trimming the hair is also acceptable; women
also cut a lock of their hair. Communal use of razors or
blades carries the risk of blood borne infections such
as hepatitis B, hepatitis C or HIV, especially considering
that many pilgrims will come from regions where such
infections are now endemic.9
To minimize this risk the Saudi Arabia Ministry of
Health advises pilgrims to avoid unlicensed barbers and
to seek licensed barber facilities at the Hajj premises.
However, many pilgrims will have their heads shaved
by unlicensed barbers, often reusing the razor blades.1
Memish et al. estimated that about 10% of the barbers
in the Kingdom of Saudi Arabia are carriers of hepatitis
C and 4% carry hepatitis B, over a tenth of whom are in
active carrier stage.10 The Ministry of Health of Saudi
Arabia encourages all pilgrims to receive hepatitis B
vaccination prior to their travel.1 The standard schedule
for administering the hepatitis B vaccine in adults 20
years and older calls for three doses of vaccine at zero,
one, and six months. An accelerated schedule consists
of vaccination at zero, one, and two months, with a
booster given 12 months after the fi rst dose.
Yellow fever
All travellers arriving from countries where there is a
risk of yellow fever transmission must present a valid
yellow fever vaccination certifi cate in accordance with
the International Health Regulations. In the absence of
such a certifi cate, the person will be vaccinated upon
arrival and placed under strict surveillance for 6 days
from the day of vaccination or the last date of potential
exposure to infection, whichever is earlier.6
Aircraft,ships and other means of transportation
arriving from areas infected with yellow fever are
requested to submit a certifi cate indicating that it
applied disinfection in accordance with methods
recommended by WHO.11
Figure 2. The tent cities in Mina provide temporary accommodation to millions of visiting pilgrims.
Varicella vaccines and traditional
vaccination schedules
Figure 1. Break-through varicella infection is varicella disease that occurs more than 42 days after vaccination following exposure to wild-type varicella zoster virus and usually results in mild illness. Nonetheless, breakthrough varicella is contagious and can lead to transmission of virus to those unvaccinated.
VA
RIC
ELLA
VA
CCIN
ES
Summary
Given the highly transmissible nature of varicella, low vaccination coverage rates generally achieved with targeted varicella vaccination in susceptible adolescents or high-risk groups are unlikely to induce substantial herd immune effects or infl uence the epidemiology of varicella disease. Accumulating evidence from countries that have implemented routine varicella vaccination of infants shows a dramatic reduction in the morbidity and mortality from varicella.
29
The currently marketed varicella vaccines are based on
the "Oka" strain of the varicella-zoster virus (VZV), which
has been modifi ed through sequential propagation
in different cell cultures. Various formulations of such
live, attenuated vaccines have been tested extensively
and are approved for use in most countries.1 Initial
clinical trials with the Oka VZV strain were initiated in
Japan by Takahashi in the early 1970s. A thermostable
formulation of the fi rst varicella vaccines (storage at
2-8°C for 2 years) has been available for more than 10
years now.
Following a single dose of the above-mentioned
vaccines, seroconversion is seen in about 95% of healthy
children but effectiveness levels can be markedly
lower.1,2,3 With regards to duration of protection, children
remained seropositive for at least 7 years in clinical
studies. In a study of 1,164 healthy children 1 to 12
years of age originally enrolled in clinical studies, an
estimated vaccine effi cacy of 93.8 to 94.6% was reported
during a 7-year period, as assessed by comparing the
observed average annual breakthrough rate with the
age adjusted expected annual incidence rate of varicella
in unvaccinated children.4 Furthermore an effi cacy rate
of 88.5% was observed in vaccinated individuals exposed
to varicella in the household, based on an historical
comparison with exposed, unvaccinated susceptible
individuals.4
From a logistic as well as an epidemiological point of
view, the optimal age for varicella vaccination is 12
to 24 months. In Japan and several other countries 1
dose of the vaccine is considered suffi cient, regardless
of age. However, other countries such as the U.S.
now recommend 2 doses of vaccine for all children,
adolescents and adults. Small studies show that when
the vaccine is administered within 3 days after exposure
to VZV, a post exposure protective effi cacy up to 80%
may be expected.5 Varicella in persons who have received
the vaccine (“break-through varicella”) is substantially
less severe than the disease in unvaccinated individuals
(Figure 1).
Current varicella vaccination recommendations
The majority of countries with a national
recommendation for varicella vaccination promote
targeted vaccination in susceptible adolescents or high-
risk groups, such as seronegative women at childbearing
age, healthcare workers, susceptible individuals with
immunosuppressed close contacts, daycare personnel
and teachers (Table 1).6 The WHO recommends that
routine childhood immunization may be considered in
countries where the disease is a relatively important
public health and socioeconomic problem, where the
vaccine is affordable, and where high (85%-90%) and
sustained vaccine coverage can be achieved. Childhood
immunization with lower coverage could theoretically
shift the epidemiology of the disease to older persons
and increase the number of severe cases in older children
and adults.1 In addition the WHO recommends that
the vaccine may be offered in any country to individual
adolescents and adults without a history of varicella,
in particular to those at increased risk of contracting
or spreading the infection. This use in adolescents and
adults entails no risk of an epidemiological shift, as
childhood exposure to VZV remains unaffected.
The strategy of targeted varicella vaccination in
susceptible adolescents or high-risk groups does not
have the potential to interrupt viral transmission and,
in the past, has been far less effective in achieving
high coverage rates when compared with childhood
programmes.7
30
Varicella vaccines and traditional vaccination schedules
Conclusion and future
Individual varicella vaccination will provide patients
with the benefi ts associated with vaccination. The
introduction of routine vaccination against varicella will
reduce the varicella case numbers, hospitalizations and
deaths due to varicella. Moreover, two doses of varicella
vaccine will achieve a better individual protection - most
strikingly against mild disease - and a better disease
control in the long term. Varicella routine vaccination
using a one-dose schedule was introduced in the USA
in 1995.8 The Advisory Committee on Immunization
Practices (ACIP) decided in June 2006 to increase the
number of varicella doses from one to two, with the
offi cial recommendations published in June 2007.9
A second dose of vaccine given universally to children
may be necessary to maximise protection against
varicella by increasing the proportion of children with
protective antibody titres and improving cell-mediated
immune responses. Indeed, a two-dose varicella
vaccination schedule for children is reported to be
associated with a higher vaccine effi cacy and a three-
times lower risk of breakthrough disease than among
individuals who received one dose (2.2% over 10 years
compared with 7.3%, respectively, p<0.001).10, 11
Educational activities are needed in order to raise
awareness among policy makers and healthcare
professionals as to the benefi ts of universal routine
vaccination against varicella.
Table 1. Varicella vaccination recommendations in different countries.6
Country Current Varicella Vaccination Recommendations
Austria Seronegative girls/women at childbearing ageSeronegative healthcare workers (especially in pediatric institutions)High-risk children (e.g. children with forthcoming transplantation or chemotherapy or immunosuppression; before immunosuppression)Seronegative family members of high-risk childrenSeronegative day-care personnel and teachers
Australia Routine childhood immunization, administered at 18 months of age, with catch-up at 10–13 yr of age
Belgium High-risk patients
Brazil Universal childhood vaccination with 2 doses: fi rst dose at 15 months of age; second dose at 4–6 yr of age (Brazilian Pediatric Society and Brazilian Immunization Society)
Canada Routine vaccination for individuals ≥12 months of age who are susceptible to varicellaSusceptible groups of adults, e.g. healthcare workers, teachers, day-care workers, householdcontacts, and other close contacts of immunocompromised individualsSusceptible individuals at high risk of severe varicella disease or its complications
Cyprus Childhood immunization from the age of 13 months onwards
Finland On an individual named patient basis
VA
RIC
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31
References1. World Health Organization. Varicella vaccines. WHO position paper. Wkly Epidem. Rec. 1998; 73: 241-248.2. Miron D, Lavi I, Kitov R, et al. Vaccine effectiveness and severity of varicella among previously vaccinated children during outbreaks in day-care centers
with low vaccination coverage. Pediatr. Infect. Dis. J. 2005; 24 (3): 233-236.3. Galil K, Lee B, Strine T, et al. Outbreak of varicella at a day-care center despite vaccination. N. Engl. J. Med. 2002; 347 (24): 1909-1915.4. Vessey SJ, Chan CY, Kuter BJ, et al. Childhood vaccination against varicella: persistence of antibody, duration of protection, and vaccine effi cacy.
J. Pediatr. 2001; 139: 297-304.5. Arnedo-Pena A, Puig-Barbera J, Aznar-Orenga MA, et al. Varicella vaccine effectiveness during an outbreak in a partially vaccinated population in Spain.
Pediatr. Infect. Dis. J. 2006; 25: 774-778.6. Vesikari T, Sadzot-Delvaux C, Rentier B, et al. Increasing coverage and effi ciency of measles, mumps, and rubella vaccination and introducing universal
varicella vaccination in Europe. Pediatr. Infect. Dis. J. 2007; 26: 632-638. 7. Sengupta N, Booy R, Schmitt HJ, et al. Varicella vaccination in Europe: are we ready for a universal childhood programme? Eur. J. Pediatr. 2008; 167: 47-55.8. Centers for Disease Control and Prevention. Prevention of varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP).
Centers for Disease Control and Prevention. MMWR 1996; 45: 1–36.9. Advisory Committee on Immunization Practices. Meeting of the Advisory Committee on Immunization Practices. June 29–30, 2006.
Available at: http://www.cdc.gov/vaccines/recs/acip/downloads/min-jun06.pdf [Accessed September 2nd, 2008].10. Seward J, Marin M, Vazquez M. Varicella vaccine effectiveness in the US vaccination program: A review. J Infect Dis 2008; 197: S82-87.11. Kuter B, Matthews H, Shinefi eld H, et al. Ten year follow-up of healthy children who received one or two injections of varicella vaccine. Pediatr. Infect. Dis.
J. 2004; 23: 132-137.
France High-risk groups: post exposure vaccination in adults (> 18 yr) without previous varicella infection; students studying medicines and paramedicines; seronegative close contacts of immuno-suppressed
Germany Administered according to a 2-dose schedule to all children at 11–14 months and 15–23 months of age when combined with MMR (MMRV)
Greece Routine vaccination for healthy children at the age of 12–18 months and for all susceptible children is recommended by the National Vaccinations Committee, but not yet offi cially endorsed by the Ministry of Health (National Vaccination Committee)
Hungary (Personal communication) On an individual named patient basis
Israel Recommendation for UMV in children through Health Maintenance Organizations, but not yet part of the routine childhood immunization schedule
Italy All susceptible individuals (national vaccination program)Priority to all susceptible adults and adolescents, and then all children living in regions able to reach high coverage rates (> 80%) in the short-term Sicily: Universal childhood vaccination in second year of life and catch-up in 12-yr-olds with no history of varicella
Japan Voluntary vaccination from 12 months of age
Lithuania Recommendation for UMV in children, but not yet part of the routine childhood immunization schedule
Malta None, but considering introducing recommendations for childhood immunization to be administered with fi rst dose of MMR vaccine
Poland Recommended for all susceptible individuals
Qatar Routine childhood immunization, compulsory at 12 months of age
Spain No offi cial recommendation, but childhood immunization from the age of 12–18 months and catch-up vaccination of susceptible adolescents at 11–12 yr recommended by the Spanish Association of Pediatrics
Sweden High-risk groupsSeronegative healthy children > 12 yr and adults who have not had varicella
Switzerland Seronegative adolescents aged 11–15 yrCatch-up for persons with no history of varicella
Taiwan Routine childhood vaccination at 12 months of age
The United Kingdom Nonimmune healthcare workersHealthy close contacts of immunosuppressed patientsOn an individual named patient basis
The United States of America
All children < 13 yr of age administered routinely 2 doses of varicella-containing vaccine (fi rst dose at 12–15 months and second dose by the age of 4–6 yr (with at least 3 months between doses)Second dose catch-up for children, adolescents, and adults who previously received 1 dose
Uruguay Routine childhood vaccination
Misconceptions about vaccinations
References1. Fenner F, Henderson DA, Arita I, et al. 1988. Smallpox and Its Eradication: The Pathogenesis, Immunology, and Pathology of Smallpox and Vaccinia. World Health
Organization, Geneva.2. Centers for Disease Control and Prevention. Impact of vaccines universally recommended for children—United States, 1990–1998. MMWR 1999; 48: 243-248.3. World Health Organisation. Six common misconceptions about immunization. Available at: http://www.who.int/immunization_safety/aefi /immuniza-
tion_misconceptions/en/ (Accessed on October 3th, 2010). 4. U.S. Census Bureau, Statistical Abstracts of the United States: 1999. Section 31. 20th Century Statistics. p. 875.5. Stewart GT. Vaccination against whooping-cough, Lancet 1977; 1: 234-237.6. Gangarosa EJ, Galazka AM, Wolfe CR, et al. Impact of anti-vaccine movements on pertussis control: the untold story. Lancet 1998; 351: 356-361.7. André FE. Vaccinology past achievements, present roadblocks and future promises. Vaccine 2003; 21: 593-595.
MIS
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33
Summary
For many families, mass vaccination programs have turned several childhood diseases such as measles, mumps, rubella, and polio, into distant memories. However, in the absence of recurrent outbreaks, public attention has begun to focus on the risks of vaccination, either real or perceived. Without balanced evidence, anti-vaccine trends can gain momentum, and vaccine coverage may fall leading to outbreaks of vaccine-preventable diseases where the disease has been previously contained.
Vaccination campaigns to control infectious
disease represent one of the greatest public health
achievements in human history. The smallpox vaccine,
fi rst developed in 1798 by Edward Jenner, resulted in the
eventual eliminaton in 1977 of this highly lethal human
pathogen from nature.1 Through effective vaccination
programs, the U.S. has seen disease incidence reduced
by 95–100% for many infectious agents including
polio, measles, mumps, rubella, diphtheria, pertussis
(whooping cough), and tetanus.2 However, the success
with vaccination in the U.S. and other countries have
also had an unexpected, self-limiting effect with regard
to public perception of disease risk.
In this modern age of communication, health-care
workers will encounter patients who have reservations
about getting vaccinations for themselves or their
children. There can be many reasons for fear or
opposition to vaccination. Some people have religious or
philosophical objections. Some people see mandatory
vaccination as interference by the government into
what they believe should be a personal choice. Others
are concerned about the safety or effi cacy of vaccines, or
believe that vaccine-preventable diseases do not pose a
serious health risk.3
All health-care workers giving vaccines have a
responsibility to listen to and try to understand a
patient's concerns, fears, and beliefs about vaccination
and to take them into consideration when offering
vaccines. These efforts will not only help to strengthen
the bond of trust between staff and patient but will also
help determine what information may be appropriate to
discuss with the patient in understanding the benefi ts of
vaccination.
Misconception 1: Diseases had already begun to disappear before vaccines were introduced, because of better hygiene and sanitation.
Statements like this are very common in anti-vaccine
literature, the intent apparently being to suggest that
vaccines are not needed. Improved socioeconomic
conditions have undoubtedly had an indirect impact
on disease. Better nutrition, not to mention the
development of antibiotics and other treatments, have
increased survival rates among the sick; less crowded
living conditions have reduced disease transmission;
and lower birth rates have decreased the number of
susceptible household contacts. However, looking at the
actual incidence of disease over the years can leave little
doubt of the signifi cant direct impact vaccines have had,
even in modern times (Figure 1).4
What are the experiences of several developed countries
after they let their immunization levels drop? Two
countries – Great Britain and Japan – cut back the use of
pertussis vaccine because of fear about the vaccine. The
effect was dramatic and immediate. In the UK in 1974 a
prominent public-health academic, Dr Gordon Stewart
(Glasgow University), became convinced, erroneously as
it was subsequently established, that pertussis vaccine
was responsible for permanent neurological damage in
infants. Professor Stewart claimed that the protective
effect of the vaccine was marginal and did not outweigh
its danger.5 His campaigning for his belief, including
television appearances, caused a dramatic fall – from
81% to 31% – in uptake of the vaccine in the UK. This,
predictably, led to a resurgence of the disease, with an
epidemic of more than 100,000 cases of pertussis and 36
deaths by 1978.6
Figure 1. The reported measles incidence per 100,000 population from 1920 to 1997.4
34
Misconceptions about vaccinations
In Japan, around the same time, a drop in vaccination
rates from 70% to 20%-40% led to a jump in pertussis
from 393 cases and no deaths in 1974 to 13,000 cases
and 41 deaths in 1979. Fortunately, in all these countries,
universal vaccination has returned and pertussis has
again been brought under control.
Misconception 2: Vaccines cause many harmful side effects, illnesses, and even death.
Currently available vaccines have a positive benefi t/
risk profi le, despite implications to the contrary in
many anti-vaccine publications. However, it must be
recognized that vaccines can indeed cause adverse
effects or “adverse reactions”. The most frequent adverse
reactions typically are benign such as transient pain,
redness and swelling at the site of injection. Systemic
reactions such as fever (sometimes leading to febrile
convulsions), malaise or headache can also occur after
vaccination. Generally, serious reactions are rare.7 Prior
to vaccination, patients should discuss the safety profi le
for the specifi c vaccines they will receive with their
healthcare professional.
Since the beginning of the 20th century, the wide use
of vaccination has produced substantial achievements
in the control of vaccine-preventable diseases. Major
victories against the spread of disease have been won
by vaccination, eradicating a disease or reducing its
incidence to rare case reports.
750
600
450
300
150
0
inci
den
ce p
er 1
00,0
00
Year
1920
1960
1992
1925
1965
1993
1930
1970
1994
1935
1975
1995
1940
1980
1996
480.5
1945
1985
1997
1950
1990
1955
1991
194.3
340.8
584.6
220.7
110.2
210.1
337.9
245.4
185.1
23.2 11.3 5.9 1.2 11.2 3.8 0.9 0.1 0.4 0.1 0.2 0.1
35
CON
GR
ESS
CA
LEN
DA
R
Congress Calendar
ISRVI 2011XIIIth International Symposium on Respiratory Viral InfectionsCairo, Egypt, March 12th – March 15th, 2011
http://www.themacraegroup.com/xiii-international-
symposium-on-respiratory-viral-infections
ISAAR 20118th International Symposium on Antimicrobial Agents and ResistanceSeoul, Korea, April 6th – April 8th, 2011
http://www.isaar.org/
ECCMID 201121st Annual Meeting of the European Society of Clinical Microbiology and Infectious DiseasesMilan, Italy, May 7th – May 10th, 2011
http://www.escmid.org/
Immunology 201198th Annual Meeting of the American Association of ImmunologistsSan Francisco, US, May 13th – May 17th, 2011
http://www.aai.org/
ESPID 201129th Annual Meeting of the European Society for Paediatric Infectious DiseasesThe Hague, The Netherlands, June 7th – June 11th, 2011
http://www2.kenes.com/espid2011/Pages/Home.aspx
ESWI 2011The fourth ESWI Infl uenza ConferenceMalta, September 11th – September 14th, 2011
http://www.eswiconference.org/
IPvC 201127th International Papillomavirus Conference and Clinical WorkshopBerlin, Germany, September 16th – September 22nd, 2011
http://www.hpv2011.org/
WSPID 20117th World congress of the World Society for Pediatric Infectious DiseasesMelbourne, Australia, November 16th – November 19th, 2011
http://www2.kenes.com/wspid/Pages/Home.aspx
