CLINICAL PRACTICE
National Consensus on Geriatric Immunization 2011
The Indonesian Society of Medical Gerontology
Department of Internal Medicine, Faculty of Medicine, University of Indonesia - dr. Cipto Mangunkusumo
Hospital. Jl. Diponegoro no. 71, Jakarta 10430, Indonesia. Correspondence e-mail to: geriatric_fkui@yahoo.com.
ABSTRAK
Meningkatnya jumlah penduduk usia lanjut akan diikuti dengan meningkatnya jumlah pasien geriatri yang
harus mendapatkan pelayanan kesehatan sehubungan dengan rentannya kelompok ini terhadap berbagai kondisi
akut gangguan kesehatan. Infeksi saluran pernapasan merupakan penyebab kematian tertinggi dan penyebab
penurunan kualitas hidup yang paling bermakna pada usia lanjut. Infeksi saluran napas atas dan influenza
sering terjadi dan berlanjut menjadi penumonia pada kelompok usia lanjut.
Tingginya morbiditas dan mortalitas pneumonia pada usia lanjut menyebabkan pencegahannya penting
untuk dilakukan. Keterlambatan diagnosis akibat kurang khasnya gejala dan tanda pneumonia pada usia lanjut
menambah perhatian akan pentingnya pencegahan pneumonia. Infeksi influenza dan pneumonia menurunkan
kualitas hidup para usia lanjut, dimana status fungsional (skor ADL) berkurang selama infeksi dan pemulihan.
Peningkatan resistensi antibiotik juga mempersulit penanganan, mengurangi kualitas hidup dan menyebabkan
angka kematian tinggi. Pemberian imunisasi untuk mencegah influenza dan pneumonia menjadi penting sebagai
salah satu upaya untuk menekan kejadian influenza dan atau pneumonia serta penyulit yang ditimbulkannya.
Konsensus ini disusun agar penduduk usia lanjut Indonesia mendapatkan imunisasi influenza dan pneumonia.
Diharapkan pada tahun 2025: 60% dari penduduk usia lanjut Indonesia mendapatkan imunisasi influenza setiap
tahun dan pada tahun 2025: 50% dari penduduk usia lanjut Indonesia mendapatkan imunisasi pneumonia.
Kata kunci: vaksinasi, virus, influenza, pneumonia, usia lanjut.
ABSTRACT
As the growth of elderly population increases, the number of geriatric patients who may demand health
care services is also increasing since the elderly are more vulnerable to various conditions of acute illnesses.
Upper respiratory tract infections are the leading cause of death and the most significant cause that impairs
quality of life in the elderly. Upper respiratory tract infections and influenza are common in the elderly and
may develop into pneumonia.
Considering the high morbidity and mortality rates related to pneumonia in the elderly, it is important to
have prevention strategies. A delay in diagnosis due to non-specific signs and symptoms of pneumonia in the
elderly has demanded greater concern on the importance of pneumonia prevention strategies. Influenza and
pneumonia impair quality of life in the elderly, resulted in decreased functional status (ADL scores) during
infection and recovery period. With increasing antibiotic resistance, the management may be complicated as
it may lead to conditions that reduce quality of life and cause high mortality rate. Therefore, immunization is
very important as the prevention strategy against influenza and or pneumonia, reducing the incidence as well
as the complication.
The consensus has been made in order to provide immunization against influenza and pneumonia for
elderly population in Indonesia. It is expected that by 2025, about 60% of the elderly in Indonesia would have
immunization against influenza and 50% of them would have immunization against pneumonia annually.
Key words: vaccination, virus, influenza, pneumonia, elderly.
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Vol 44 • Number 1 • January 2012
National Consensus on Geriatric Immunization 2011
INTRODUCTION
pneumonia may also impair quality of life in the
elderly, resulted in decreased functional status
(ADL scores) during infection and recovery
period.13 With increasing antibiotic resistance, the
management may be complicated as it may lead
to conditions that reduce quality of life and cause
high mortality rate.14,15 Therefore, immunization
is very important as the prevention strategy
against influenza and or pneumonia, reducing
the incidence as well as the complication. The
elderly in nursing home shall need greater special
attention.
The consensus has been made in order to
provide immunization against influenza and
pneumonia for elderly population in Indonesia.
It is expected that by 2025, about 60% of the
elderly in Indonesia would have immunization
against influenza and 50% of them would have
immunization against pneumonia annually.
The number of elderly population in Indonesia
is increasing and it will reach the highest
acceleration in the world by 2020, i.e. 41.4%
compared with the rate in 1996.1 By the year
2025, there will be 25.5 million octogenarians
because of longer life expectancy and increasing
number of older people in society.2,3 Increasing
number of the elderly will be followed by greater
number of geriatric patients who may demand
health care services as they are more vulnerable
to various conditions of acute illness. One of
the illnesses includes respiratory tract infection,
which is the leading cause of death and the most
significant cause that impairs quality of life in
the elderly.
The elderly is more vulnerable to infection as
they own impaired physiological immune system
and reduced lung function, i.e. suppression
of the cough reflex and decreased function of
mucocilliary epithelial in the respiratory tract;
therefore, the risk of pneumonia in the elderly
increases. Decreased cell-mediated immunity
as shown by increasing annergic reaction,
slower response of lymphocyte proliferation, as
well as reduced function of helper T-cells and
B- lymphocytes in the elderly will cause lower
immune response against infections.4,5
Upper respiratory tract infections and
influenza are common in the elderly and may
develop into pneumonia. The prevalence of
influenza may reach 5-20% of population each
year along with high mortality rate, especially
among neonates and the elderly population.6
Therefore, vaccination may become a primary
prevention strategy against the death and
complication in the elderly.7,8
In 2003, the mortality rate related to
pneumonia is still as high as 30.3% 9,10 of
all hospitalized elderly patients. In 2000, a
proportion of 54% hospitalization and 90% of
death in the elderly over 65 years in the United
States were caused by pneumonia.11 Until 2002,
many elderly patients have died from pneumonia
(200 out of 100,000 elderly).12
Considering the high morbidity and mortality
rates related to pneumonia in the elderly, it
is important to have prevention strategies. A
delay in diagnosis due to non-specific signs
and symptoms of pneumonia in the elderly has
demanded greater concern on the importance of
pneumonia prevention strategies. Influenza and
INFLUENZA IN ELDERLY
Influenza is acute upper respiratory tract
infection, which may be caused by influenza
virus, parainfluenza virus, adenovirus and
respiratory syncytial virus (RSV). During
seasonal epidemics or the rainy season, most
cases are caused by influenza virus. The Flu
Pandemic with extremely high death rate
worldwide occurred in 1918. In Asia, there
were reports on very high mortality rates in Iran,
Indonesia and Singapore; it was estimated that
approximately 3 million people died. At that time,
approximately 114,000 (out of 3,250,000 people)
in Madagascar died from influenza outbreak.
The second pandemic (influenza virus A/H2N2)
(1957) resulted in a sharp increase of death rate.
In Europe, it reached 30% of population; while in
Costa Rica and India, it affected 68% and 19% of
population, respectively. The influenza virus A/
H3N2 pandemic in 1968-1969 also causes high
morbidity and mortality rate around the world.
The Asian reports indicated that 8.4% of total
population in Madras, India had been infected
by the disease, which was developed through the
entry to sea harbor.16,17
Influenza virus is a virus belonging to the
family Orthomyxoviridae of RNA viruses.
The structure of virus consists of a nucleus
made of ribonucleic protein (to form helical
structure of nucleocapsid) and covered by lipid
and glycoprotein coat. Each virion contains
8 RNA molecules that accounts for encoding
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the synthesis of 10 different types of proteins.
Among those are two glycoprotein expressed on
the surface of virus particle, i.e. hemagglutinin
and neuraminidase. Hemagglutinin, the antibody
target of the available vaccine, has a role in
attaching virus particle to neuraminic acid
mucopolysaccharide (sialic acid) on the surface
of respiratory epithelium. The location is a very
important site of viral penetration and replication.
After the virus particle successfully penetrates
into epithelium and the replication takes place,
a new virion will be expressed on the surface
of epithelial cells and bound to sialic acid.
Neuroamidase, which is the target of antiviral
agents, the anuroamidase inhibitors, subsequently
breaks the bond between neuraminic acid and
hemagglutinin resulting in the release of virion
from epithelial cells and cause further infection
to other epithelial cells.
M2 protein, which is unique to influenza
virus A, is the active site that interact with M2
inhibitor agents such as amantadine, loratadin
and rimantadin. It is the site where the virus
replication is stopped.
Influenza viruses are classified into type A, B
and C. Type C is non-virulent. Type B particularly
causes infection in children and it has antigenic
stability; therefore most adults, including the
elderly, are not susceptible to the virus.
Type A influenza viruses attack people of
all ages and easily alter its antigenic properties,
either on the hemagglutinin or neuramidase
site. The altered antigenic properties may
appear as antigenic drift (due to nucleotide
substitution) or antigenic shift (due to genetic
recombination with other type A influenza
viruses. The abovementioned antigenic change
causes the virus remains undetected by immune
response, both by memory T cell or antibody
(immunoglobulin). Therefore, vaccination of
one strain of type A influenza will not provide
protection against other strain.4 Until now, there
are three influenza A virus subtypes (strain), i.e.
H1N1 strain (that cause the 1918 flu pandemic
or Spanish influenza), H2N2 strain (the cause
the pandemic of 1957) and H3N2 strain (that
currently cause significant morbidity and
mortality rate).18 Moreover, the strain of type B
influenza viruses, both B/Victoria/2/87 and B/
Yamagata/16/88 lineages are circulating strains
in the environment 19
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For vaccination, WHO recommends two
influenza type A subtypes (H1N1 and H3N2
strain) and one influenza type B subtype.20
The recommended vaccine composition for the
2008-2009 Northern Hemisphere (November
2008 – April 2009) and the 2008-2009 Southern
Hemisphere (May – October 2009) influenza
season includes the A/Brisbane/59/2007 (H1N1)like virus, A/Brisbane/10/2007 (H3N2)-like virus
and B/Florida/4/2006-like virus.
Current data demonstrates that WHO
recommend vaccine composition for northern
hemisphere region in 2009, which begins
in November 2009 to April 2010, i.e. A/
Brisbane/59/2007 (H1N1)-like virus, A/
Brisbane/10/2007 (H3N2)-like virus,
and B/Brisbane/60/2008 virus.20 The B/
Malaysia/2506/2006 virus, B/Florida/4/2006 or
B/Brisbane/60/2008 which is in the vaccine that
now available in Indonesia were one of strain B/
Victoria/2/87. Both the B/Malaysia/2506/2006
and B/Florida/4/2006, which is available vaccine
in Indonesia, are of the B/Victoria/2/87 lineage.
Epidemiology
Type A influenza viruses have two patterns of
spread. The first pattern is epidemics in certain
geographical area during rainy/winter season,
which occurs for several weeks. The second
pattern has pandemic characteristic (occurs
whole year round) and usually caused by virus
that undergoes antigenic shift. Recognized host
are pets and domestic animals (including birds)
because of its closeness with human habitat,
which highly facilitate genetic recombination
resulting in genetic shift. The pandemic often
occurs in Asian countries.
Documenting the morbidity, mortality and
the impact of influenza is not easy; especially
in tropical countries where the rainy season
does not begin at fixed date like in subtropical
countries. Data documentation in pandemic
countries (such as Asia) is difficult because
pandemic change caused by type A influenza
which has antigenic drift is difficult to track. The
similarity of signs and symptoms of influenza to
those in other diseases of the respiratory track,
as well as the difficulty in obtaining confirmed
virological diagnosis make the documentation of
influenza statistics even harder. Epidemiological
observations comparing the incidence of
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National Consensus on Geriatric Immunization 2011
influenza of certain period and the incidence of
other period of time is the common method that
has been utilized.17
In 2003, 82% of influenza outbreak in Thailand
was dominated by H3N2 strain.21 In Indonesia,
national data on the incidence of influenza has not
been established. Hospital documentations and
medical reports in the year of 2000 indicated that
influenza was one of the top 10-common illnesses
in Indonesia. National Health Survey 2001
demonstrated that upper respiratory tract infection
was the third most common disease (24%) in
Indonesia.22 About 97% of influenza outbreaks
were caused by H3N2 strain.23 The prevalence of
influenza may reach 5-20% of population each
year along with high mortality rate, especially
among neonates and the elderly population. In the
population over 50 years of age, the mortality rate
is increasing with age.6
It has been reported that viral resistances to
amantadine (when used for prophylaxis) were
76%, 27%, and 36% in 2005, 2006 and 2007,
respectively.24 Amantadine resistance of H3N2
reached 99% in 2007-2008. The resistance to
neuraminidase inhibitors used for influenza
prophylaxis has also been reported; therefore, the
use of both amantadine and neuraminidase for
prophylaxis are not recommended. Initial spread
begins through viral transmission of secreted
droplet in the infected respiratory tract, with
incubation period ranges from 1-5 days, before
it becomes symptomatic after the average 2 days
of incubation period. The first symptoms in the
elderly usually are loss of appetite, weakness,
fatigue, and malaise. Other symptoms may include
symptoms of acute respiratory tract infection such
as fever, myalgia, and headache. The fever may
be extremely high and last for at least three days.
Muscle pain may predominate in extremities,
orbital area, and the trunk. The symptoms may
be exaggerated by cough (initially appears as a
non-productive cough), sore throat and coryza.
On physical examination, the elderly will appear
severely ill, had redness of the conjunctiva
and sometimes accompanied with lymph node
enlargement around neck (with tenderness); clear
nasal secret (except when superimposed with
bacterial/ secondary infection).
influenza. Signs and symptoms (usually appear
5-7 days after the initial symptoms) are worsened
cough, dyspnea with wheezing, and unresolved
fever along with productive purulent phlegm. It
will result in reduced functional status, prolonged
recovery time (post-influenza asthenia) with high
dependency rate, or even sepsis and death. The
manifested non-specific signs and symptoms
(delirium syndrome, postural instability
and fall) may cause further complication
of influenza in the elderly. Microorganisms
that may cause pneumonia as complication
of influenza are opportunistic bacteria such
as Streptococcus pneumonia, Haemophilus
influenzae andStaphylococcus species. Although
it is uncommon, other complications such as
rhabdomyolysis, myoglobinuria, myocarditis,
and pericarditis with tamponade may also occur.
Influenza complication in geriatric
patient usually will also affect the patient’s
dependency level. Barker et al (2004) reported
that there was decreased ADL (activities of
daily living) capacity in geriatric patient with
type A influenza or respiratory syncytial virus
infection.13 Dependency in taking a bath, mobility,
performing household activity and personal drug
management were increased from 25 to 31%; 7 to
11%; 18 to 26%; and from 3 to 12%, respectively.
Comorbidity and reduced functional capacity of
all body systems in the elderly with influenza
infection will exaggerate their general condition
resulting in weakness (which may include
immobility and deconditioning). Immobility in
the elderly due to infection will cause decreased
mucus secretion, ineffective cilia movement,
and ineffecient cough mechanism, which may
deteriorate the respiratory infection.
Complication of influenza in the elderly is
more likely to be developed in patients with
comorbidities such as diabetes, COPD (chronic
obstructive pulmonary disease), bronchiectasis
and coronary heart disease. Older age and poor
oral hygiene are other important factors that may
induce complications.
Complication
Respiratory tract hyperreactivity and
pneumonia are the common complication of
PNEUMONIA IN ELDERLY
Pneumonia Epidemiology
Until now, pneumonia is the leading cause
of death in hospitalized geriatric patient. The
prevalence of pneumonia at acute geriatric ward
of Cipto Mangunkusumo Hospital in 2000 was
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54.8% with mortality rate reached 32.5%. In
2001, the prevalence increased to 61.6% with
mortality rate of 32.9%. In 2003, the prevalence
of pneumonia in geriatric patients decreased
into 52.2%, with mortality rate that remained
high of 30.3%.9,10 In 2000, a proportion of 54%
hospitalization and 90% of death in the elderly
over 65 years in the United States were caused by
pneumonia.11 Until 2002, many elderly patients
have died from pneumonia (200 out of 100,000
elderly).12 In 1998, Niederman in New York
reported community data that the death rate
related to pneumonia in elderly patients was 9
out of 100,000 people (without comorbidity)
and the death rate may increase into 217 patients
out of 100,000 elderly people when there were 3
comorbidities.25
Pneumococcal resistance to antibiotic is one
of the other important issues. Parsons (2002)
reported that the incidence of pneumococcal
resistance to penicillin varied from country
to country: Spain 65.6% (1999-2000), United
States 23% (1998), England 9% (1998), and
Australia 9% (1994).15 The resistance contributes
to high mortality rate and the development of
complications related to pneumonia such as
meningitis and sepsis (invasive pneumococcal
pneumonia = IPD). In Europe and United
States, the incidence of invasive pneumococcal
disease ranges between 25 and 100 per 100,000
cases with the highest age- specific incidence
rate in the elderly.21 Mortality rate related to
IPD may reach 40% in patients aged >85 years
and 20% in patients aged >65 years. The issue
of antimicrobial resistance apparently may
not only restricted to penicillin, but also to
other antimicrobial agents such as macrolides,
chloramphenicol, trimetoprim-sulfametoxazol,
and cephalosporin.14
The transmission of pneumonia in the elderly
patients is similar to the young adults. However,
several aspects need to be concerned. First,
oropharynx is the common site of microbial
colonization that may increase the risk for
pneumonia. Malnutrition, poor oral and dental
hygiene also contribute as risk factors for
recurrent pneumonia.10
The elderly who lives in nursing home will
carry greater probability to get pneumonia. It
may occur since there is higher microbial density
in the population and most of inhabitants are
more vulnerable compared to those who live
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with their family in the community. Therefore,
pneumococcal vaccination for the elderly is one
of the prevention strategies recommended by
WHO, CDCP and JVCI since 2003 up to now.
Clinical Course
Initial symptoms of pneumonia in the elderly
are not specific. The common constitutional
symptoms are weakness, loss of appetite and no
eagerness to do activities. Frequently the families
who live with them, or even the patient, do not
realize that the infection has begun, which would
developed into worse condition. The classic
signs of cough and dyspnea with fever are hardly
found, but it may be present. Patients are usually
admitted to hospital due to fall, unconsciousness
or exaggerated dyspnea. The non-specific clinical
manifestations in elderly patients with pneumonia
may lead to a delay in diagnosis, which may
be misdiagnosed, resulting in unsatisfactory
outcome.
Physical examination may reveal acute
confusional state or delirium syndrome. Mild
fever or even mild hypothermia may occur. It
is not uncommon to find patients admitted to
hospital without any fever. Tachypnea and altered
consciousness may also be found. Auscultation
examination may reveal rales or wheezing.
Complication
The aforementioned discussion has indicated
that a delayed diagnosis or misdiagnosis of
pneumonia in elderly patients is commonly
occurs that may result in unsatisfactory outcomes.
In many cases, the patient may experience
various complications including respiratory
failure, respiratory acidosis, sepsis and even
death. Nevertheless, when the patient has
managed to overcome the acute phase, the
healing process may be prolonged causing high
medical and hospitalization cost. Moreover, the
patients usually have impaired functional state,
which cause great dependency upon other people
or having high dependency level to perform their
activities of daily living
As have been mentioned before, pneumonia
in geriatric patients often has clinical presentation
of postural instability, which may cause fall.
Femoral fracture, immobilization, incontinence,
contracture, decubitus and sepsis are conditions
commonly found in geriatric patients with
pneumonia. Such conditions may lead to
impaired quality of life in the elderly patients.10
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National Consensus on Geriatric Immunization 2011
INFLUENZA VACCINATION
Following the large-scale trial by Nichol,
experts from different countries have also
conducted studies to evaluate the benefit of
immunization. An important trials by Christenson
et al. in 2001 who conducted a study in Stockholm
involving 100,242 elderly people (who received
vaccination in 1998). It was an interventional
and prospective study, which also carried out
controls on the affecting factors. The study
result showed that there was a 46% decrease
of incidence (per 100,000 elderly people each
year) regarding hospitalization in elderly who
had received influenza vaccination. Moreover,
the incidence of hospitalization in elderly
who had received pneumonia vaccination has
decreased as much as 26%. The immunization
has also significantly reduced the incidence of
pneumonia complication, i.e. 36% decrease for
pneumococcal pneumonia and 52% decrease for
invasive pneumococcal disease.Total mortality
rate was also lower in the group that received
vaccination (15.1 vs 34.7 per 1000 elderly
population or 57% decrease).32
A recent prospective study, which evaluated
the benefit and efficacy of influenza and
pneumonia vaccination of elderly population in
Sweden has also reported reduced morbidity as
much as 62% and decreased hospitalization rate
up to 69% (p< 0.001) in 2003-2005, both for the
groups aged 65-74 years and over 80 years.33
There is a shorter length of hospitalization
related to influenza with/without pneumonia in
elderly people aged less than 80 years who has
been vaccinated. Groenwold (2009) has also
reported reduced mortality risk in elderly who
has been vaccinated after controlling age, sex,
comorbidities, and previous access to health
care.34
A large scale cohort trial (n = 260,000) in
2007 reported lesser decrease after controlling the
confounding factors with differences on mortality
from 50%, 46% and 42% into 14%, 19%, and
1% in the year of 1998 – 2000. 35Another large
scale cohort study by Nichol (2007) involving
713,872 elderly has reported that there was 27%
lower risk for hospitalization and lower risk on
mortality as much as 48%.36
Several studies indicate that influenza
vaccination may also lower the incidence of
hospitalization caused by chronic respiratory
disorder, heart failure, and stroke.37,38 Nichol
et al (2003) reported that influenza vaccination
Benefit
The vaccination is directed especially
for high risk groups such as the elderly, who
lives in the community or nursing homes and
patients with chronic disease.The benefit of
influenza vaccinations may be considered as
medical and economic advantages. Medical
advantages include lesser incidence of influenza
complication (such as pneumonia), lower
incidence of hospitalization due to respiratory
tract infection and other diseases related to it
and reduced hospital mortality rate related to
respiratory tract infection. Economic advantages
may be evaluated based on the lesser expense
as a result of vaccination, including reduced
hospitalization cost as well as reduced treatment
cost in the outpatient unit.26 Various studies have
demonstrated the benefit of immunization in
decreasing morbidity and mortality.
Influenza vaccination can significantly
decrease morbidity rate (the hospitalization rate
related to pneumonia and influenza per 1000
elderly population are 4.8 vs 5.7 [p < 0.02]) and
reduce mortality rate (the mortality rate per 1000
elderly population are 3.4 vs 5.4 [p < 0.001]) after
controlled trials (controlled age, sex, comorbidity
and previous access to health care provider.27
A study in 1898 elderly patients with chronic
pulmonary diseases reported that influenza
vaccination has relatively good effect on
outpatients rate (OR 0.64) and hospitalization rate
(OR 0.48).28 The study also provided evidences
that immunization may reduce mortality rate (OR
0.3) after demographic factors and comorbidities
had been controlled. Similar result has also been
demonstrated by Ikematsu et al (October 1999),
who reported that influenza vaccination do not
need booster injection on concurrent month since
there was no significant benefit compared to once
a year immunization.29 Voordouw et al. found that
the first vaccination lowered mortality risk as
much as 10% and revaccination in the following
year will decrease mortality risk of 24%.30
Regarding the medical cost savings, Nichol
demonstrated that the hospitalization cost in the
group receiving immunization was lower than
the group without immunization (66% decrease
vs 47% [p< 0.005]). Similar issue has also been
indicated by Mullooly et al. demonstrating that
each vaccination for high-risk elderly will save
medical cost of 6.11 USD.31
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lowered morbidity rate of heart disease, CVD and
pneumonia+influenza as much as 19%, 23% and
32%, respectively (p<0.001) and also reduced
death from various causes as much as 50%
(p < 0.001) after controlling the demographic
characteristics and comorbidities (lung disease,
stroke, diabetes, renal disease, rheumatism,
vasculitis, malignancy, dementia, hypertension,
atrial fibrillation and dyslipidemia).37
The result has also been supported by recent
study conducted by Christenson in 2008, which
reported that the incidence of hospitalization
per 100,000 patients with heart failure has
decreased as much as 62% (p<0.01) in elderly
patients following the influenza vaccination. The
elderly who had received influenza vaccination
showed lower percentage of hospitalization due
to heart failure compared to the elderly who
got influenza and pneumonia vaccination. The
incidence of hospitalization related to pneumonia
has also decreased in the elderly who had only
received influenza vaccination (49% decrease
in pandemic season and 63% in non-pandemic
season [p<0.001]).33
Although it was assumed that with increasing
age, influenza vaccination in patients aged >80
years would not be as effective as vaccination
in patients aged 65–79 years, but a study by
Nichol (2004) in more than 567,000 subjects has
found comparable effectiveness in both groups
during influenza season in the year of 1996-1997,
1997 – 1998, 1998 – 1999, 1999 – 2000 (OR of
influenza in patients aged 65-74 years were [0.44;
0.62; 0.58; and 0.61], respectively and OR in
patients aged > 85 years were [0.40; 0.63; 0.48;
and 0.51]).39
Similar study has also been reported by
Wongsurakiat et al in Thailand (2004), where
the incidence of upper respiratory tract infection
related to influenza in 125 elderly with COPD
was 6.8 per 100 people each year compared to
the control group (28.1 per 100 people each year)
(Relative Risk [RR] 0.24 [p<0.005]; vaccine
effectiveness 76%).40 Similar effectiveness
has also been reported in the interventional
prospective study conducted by Chen et al in
Taiwan (2004).12 The death rate per 100,000
elderly people due to chronic bronchitis,
emphysema and asthma has been reduced from
93.62 in 1997 into 65.87 in 2002. It is consistent
with the influenza immunization program, which
has been implemented since 1997 until now.
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There was a study providing evidences on
effectiveness bias of influenza vaccination. It
demonstrated lower mortality risk during the
period prior to influenza season (RR = 0.39)
and higher risk after the influenza season (RR=
0.74), compared to the risk during the influenza
season (RR=0.56).41 However, the study was
comparing non-specific final result; thus, it has
not been clear whether the working diagnosis
was really caused by influenza virus or by other
pathogen that may reduce the effectiveness and
efficacy of vaccination (CDC MMWR 2008). It
should be noted that difference on virus strains
between those available in environment and virus
strain contained in the vaccine during the given
period may affect the efficacy and effectiveness
of the vaccine. Center for Disease Control (CDC)
also stated that the incidence of infection in
the elderly is affected by the impaired immune
response against the vaccination itself due to
aging rather than incapacity of the vaccine in
providing protection against influenza. The fact
is supported by Skowronski et al who conducted
review on various literatures and they concluded
that there was no compelling evidence to support
more rapid decline of the greater impairment of
immunity in the elderly.42
The only double-blind controlled trial in the
elderly of the community reported that efficacy
of influenza prevention reached 58% when the
vaccine and circulating virus strains were wellmatched.43 However, the efficacy might be lower
among those with older age (over 70 years).
The vaccine effectiveness against respiratory
infection in the elderly who lived in the nursing
home reached 20-40%,44,45 and it might be not
significant if the circulating and vaccine virus
strains were different.46,47 Some studies have
provided evidences on the effectiveness against
death due to influenza as high as 80%.7
WHO reported reduced hospitalization
rate up to 39% and decreased mortality rate
of 39-75% in the elderly who lived in the
community following the influenza vaccination.
Hospitalization rate for elderly in nursing homes
has also significantly reduced up to 50%.20
Crutchfeld (2001), reported that since WHO
(World Health Organization) has published the
recommendation of vaccination for elderly, the
influenza immunization coverage in the United
States is only about 58.5%. Therefore, in 2002,
CDC (Center for Disease Control and Prevention)
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National Consensus on Geriatric Immunization 2011
and CMS (Center for Medicare and Medicaid
Services) has issued an investigation protocol
to increase influenza immunization coverage,
with the target of 90% coverage by 2010. The
protocol has become a standard health service
in prevention strategies against influenza and
pneumonia and a standard quality of health
professional services.6,48
Until now, influenza vaccination has been
extensively used in more than 50 developed and
developing countries. One year following WHO
recommendation on influenza vaccination for the
elderly in 2000, there has been more than 350
doses of vaccine per 1000 elderly population
in Canada. It is followed by the United States,
where the vaccine reached 256 doses per 1000
elderly population, and Australia as well as
Western European countries with 183-197 doses
per 1000 elderly population. Korea and Japan
have provided 147 and 109 vaccination doses
per 1000 elderly population, respectively. Other
Asian countries which already implemented the
immunization program for elderly are: Taiwan,
Lebanon, Hong Kong, Singapore and Uni
Arabian Emirates.49
Table 1 contains a compilation of various
studies conducted since 2001 that shows the
benefit of influenza immunization.
Risk
Local side effects, which are found in less
than one-third of cases, may present as local pain
that usually will be alleviated in 2-3 days without
any specific medication. Systemic side effects
that may occur are fever, malaise, headache,
myalgia, arthralgia, which may last for 6-12 hours
following the vaccination and will be resolved in
one to two days.
Individuals who have had allergic responses
to egg protein may experience hypersensitivity
reaction; therefore those who were allergic to
eggs should not receive influenza vaccine (CDCP,
2004).
Chen (2004) reported that among 1,250,053
elderly subjects who had been vaccinated in 2002,
7.1% of them reported side effect of restlessness
(fatigue). While the side effects of local pain
and headache were reported of 4.9% and 4%,
respectively. The side effects are temporary and
will be resolved without any specific therapy.
Table 1. Compilation of various studies on the benefit of influenza immunization
Author (year)
Design and Methods
Results
p/CI
Christenson, et al
(2001)
-- Interventional,
prospective
-- n = 100.242 elderly
-- Incidence/100 hospitalization rate of elderly:
-- influenza vaccinated group i46%
-- pneumonia vaccinated group i29%
-- Incidence of pneumonia complication i36%
-- Invasive pneumococcal disease i52%
-- Total death in the group receiving immunization
i57%
CI : 34;56
CI : 24;34
CI : 3;58
CI : 1;77
CI : 55;60
Nichol, et al (2003)
-- Cohort
-- n = 286.383
-- Risk of heart disease hospitalization i19%
-- Risk of CVD hospitalization i32%
-- Death due to any causes i50%
p<0.001
p<0.001
p<0.001
Vordouw, et al
(2004)
-- 6-year cohort
-- n = 26,071
-- First vaccine g mortality risk i10%, HR 90%
-- Revaccination in the next 1 year h mortality risk
i24%, HR 0.76
-- During epidemic g mortality risk i28%, HR 0.72
ratio
CI : 0.78;1.03
CI : 0.70;0.83
CI : 0.53;0.96
Vordouw, et al
(2004)
-- 6-year cohort
-- n = 26,071
-- Age > 70 yr g mortality i
-- Vaccination coverage 70% g prevent 1 death for
every 302 vaccinations
p<0.05
Nichol, et al (2004)
-- Cohort (1996-2000)
-- n > 567,000 elderly
subjects
-- Aged 65-74 yr: OR = 0.44; 0.62; 0.58; 0.61
-- Aged >85 yrs: OR = 0.40; 0.63; 0.48; 0.51
-- Not significantly different between both groups
p<0.05
Wongsurakiat et al
(2004)
-- Influenza vaccine
benefit
-- n = 125 elderly
patients with COPD
-- Influenza vaccine group: incidence 6.8 per 100
individuals-year
-- Control group: 28.1 per 100 individuals-year
-- RR = 0.24
-- Vaccine effectiveness 76%
p<0.005
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Author (year)
Acta Med Indones-Indones J Intern Med
Design and Method
Results
-- Interventional
prospective
-- 124.702 subjects
receiving influenza/
pneumonia
vaccination
-- 134.045 control
group
-- Risk of hospitalization due to IPD and pneumonia
in vaccinated group i (OR=0.67 vs OR=0.79)
-- Risk of mortality in the group receiving influenza
vaccination i (OR=0.88)
-- Risk of mortality in the group receiving two or
more vaccine i (OR=0.65)
-- Length of hospitalization in vaccinated group was
shorter
Chen Y-H (2004)
-- Interventional
prospective
-- 1.250.000
vaccination
-- Mortality rates due to chronic bronchitis, lung
emphysema, and asthma decreased from
93.62/100.000 (in 1997) to 65.87/100.000
(in 2002)
Nichol KL et al
(2007)
-- Cohort
-- n = 713.059elderly
subjects in
community
-- 27% lower risk for hospitalization due to
pneumonia or influenza
-- 48% lower mortality risk in groups of all age
OR 0.73
CI : 0.68-0.77
OR 0.52
CI : 0.50-0.55
Christenson B et al
(2008)
-- Interventional
prospective
-- n = 41,059 (in
2003), 14,799 (in
2004), 8,843 (2005)
-- Lower morbidity of 20-62% and lower
hospitalization rate of 13-69% in subjects aged
65-79 yr
-- Lower hospitalization rate of 46% in subject aged
>80 yr
-- Greater decrease of hospitalization rate in
subjects receiving influenza vaccination only
(62%) compared to those receiving influenza +
pneumonia vaccination (29%)
-- Lower morbidity and hospitalization rate in
subjects with IPD (68% and 40%) and subjects
with pneumococcal pneumonia (13% and 38%)
p<0.001
-- Risk of mortality i during epidemic season
(OR=0.58)
-- Effectiveness in elderly subjects aged >75 yrs i
(OR=0.66)
CI : 0.56-0.72
Christenson (2004)
Groenwold RHH et
al (2009)
-- Interventional
prospective
-- n = 50,906 elderly
subjects
PNEUMONIAE VACCINATION
Benefit
Various studies have reported the benefits
of pneumococcal polysaccharide vaccination,
from the oldest serotype 2-valent vaccine to the
latest serotype 23-valent vaccine. Christenson
(2001) reported that the incidence of pneumonia
in the group receiving vaccine has decreased as
much as 29% compared to the non-vaccinated
group; moreover, the incidence of invasive
pneumococcal disease has been lowered up
to 52%.32 Similar results has been reported by
Wagner in 2003 who demonstrated lower risk
for pneumonia in vaccinated group than nonvaccinated group (OR 0.279; p<0.0001) after
controlling demographic characteristics, body
mass index and various comorbidities (COPD,
coronary heart disease, heart failure, diabetes
mellitus and malignancies). Mortality risk has
also decreased in vaccinated group (OR 0.331;
p<0.0001). A double-blind trial by Koivula et al
86
p/CI
CI : 0.55;0.82
CI : 0.75;0.84
CI : 0.69;1.11
CI : 0.54;0.78
p<0.01
CI : 0.43-0.69
p<0.001
p<0.001
CI : 0.50-0.86
demonstrated that in the elderly subjects aged
>60 years with comorbidities, there was lower
risk for pneumonia in vaccinated group than those
who had not receive vaccination (there was 59%
protective efficacy). Gailat and Fedson (1999)
have also reported that pneumonia vaccination
in the elderly will provide a relatively great
protection (77% protective efficacy). However,
it should be noted that the critical appraisal of
these studies showed that there was indistinct
classification of diagnosis that may lead to
misclassification and ascertainment bias.50,51
Regarding the aspect of pneumonia
vaccination, significant benefit has not been
shown in every study. Simberkoff (1986) and
Ortqvist (1998), in their double-blind trials
could not prove the benefit of pneumococcal
polysaccharide vaccine.51,52 A meta-analysis by
Huss in 2009 concluded that pneumococcal
polysaccharide vaccine is not effective as
prevention strategy against pneumonia. Other
experts who disagree with pneumonia vaccination
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National Consensus on Geriatric Immunization 2011
are: Moore et al (1999), who reported that
the response of antibody production and the
effectiveness of vaccination are lower in elderly,
especially in those aged >75 years; Mercola
(2003) based on his study results indicated that
there was no correlation between pneumonia
vaccination and lowered risk for pneumonia of
any etiology. Vaccine antigen will only stimulate
B lymphocyte to produce antibody, but it has no
effect on T lymphocyte.14
In January 2009, the Joint Committee on
Vaccination and Immunization (JVCI) has
proposed that pneumococcal conjugate vaccine
(serotype 7-11) may provide greater promising
results than pneumococcal polysaccharide
vaccine, which has been used in elderly vaccination
program around the world). While waiting for
results of the study, JVCI recommended that
pneumococcal polysaccharide vaccination is still
relevant; however, it also has been considered
to alter the implementation on type of conjugate
vaccine. The use of 23-valent vaccine as a booster
after conjugate vaccine injection may improve
the vaccine effectiveness.53
Although the benefit of pneumonia
immunization using the 23-valent vaccine is
still being debated, WHO issued a stipulation
that pneumonia vaccination in the elderly is
quite effective to protect healthy elderly subjects
against invasive diseases (pneumonia with
complications such as meningitis, septicemia,
and pneumococcal pneumonia). It is supported
by an analysis on serotype distribution, which
demonstrated that the greatest percentage of
invasive disease is still caused by 23-valent
serotype.54
Pneumococcal vaccination is still
recommended in elderly vaccination program in
the United States, 2009 and it has a priority on
healthy elderly population who live in nursing
home (CDCP, 2008). The study by Christenson
et al (2004), which was a large scale prospective
interventional study in Sweden with 124,702
elderly subjects who had received influenza and/or
pneumonia vaccination (134,045 elderly subjects
in control group) showed results supporting result
on implementing vaccination.55 The study found
that there was a lower risk of hospitalization
due to influenza, pneumonia and IPD (invasive
pneumococcal disease) in the vaccinated group
compared to the non-vaccinated group. It also
found that the mortality risk due to pneumonia
was lower in the group receiving influenza
vaccination, although it was not significant.
However, in subjects who had received two
kinds of vaccinations, the risk was significantly
lower. The length of hospitalization of those
who received vaccination was significantly
shorter than those without vaccination. It is
also important to notice that in order to control
confounding factors, a survey in 10,000 elderly
subjects has been conducted and the baseline
data for vaccinated group are as follows: older
mean age, more elderly lives in nursing homes,
more comorbidities; overall, both group were
not only comparable, but also at ‘lower’ starting
point compared to the control group. Therefore,
the results were underestimated from the true
results. In conclusion, immunization for the
elderly using influenza and pneumonia vaccine
provides a relatively effective protection against
morbidity and mortality related to influenza,
pneumonia and IPD.
Meta-analysis on 11 blind-controlled trials
and 2 non-blind controlled trials reported that
the risk of systemic infection by pneumococcal
reduced to 83% and the risk of infection caused
by all types of pneumococci reached 73% of
effectiveness. 56 The current comprehensive
meta-analysis by Morbeley in 2008, which
evaluated 15 Randomized Controlled Trial
(48,656 participants), and 7 non-RCT (62,294
participants) reported a strong evidence on
the efficacy of polysaccharide vaccine against
invasive pneumococcal disease (OR 0.25, CI
0.15-0.46, I2=0%); however, the efficacy against
all-cause pneumonia cannot be concluded because
of wide variation on statistical differences. It did
not provide evidences on lower efficacy in the
elderly or in patients group with chronic disease,
which were statistically not significant in the
study.57
Recent findings reported by Lamontagne
et al in 2008 demonstrated that pneumococcal
vaccination is associated with 50% lower
incidence of myocardial infarction, especially in
the group that has receive vaccination more than
2 years (OR after control 0.33, CI 0.29–0.46),
which may occur through the mechanism of LDL
oxidation and prevention of foam cells production,
which act as precursors of atherosclerosis. 58
However, a double-blind, controlled trial with
greater power is still necessary since the study
still has bias on greater number of healthy
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The Indonesian Society of Medical Gerontology
Acta Med Indones-Indones J Intern Med
subject in the control group.59 Another study
conducted in 84 patients with chronic lung
disease demonstrated a great increase of sera IgG
level following the polysaccharide vaccination,
especially the 23-valent. Such increase will
remain until 3 years.60 It provide evidence that
there is an increase of immunogenicity following
the pneumococcal polysaccharide vaccination.
Risk
Side effects of pneumonia vaccination
includes local (20-30%) or systemic (<1%)
reaction. Honkanen et al reported that 93%
subjects experienced localized skin redness
without tenderness after four days (284 subjects
in the group receiving influenza vaccination only
and 441 subjects in the group with influenza and
Table 2. Compilation of studies on the benefit of pneumonia polysaccharide immunization
Author (year)
Koivula (1997)
Design and Methods
Double blind trials
Gailat & Fedson
(1999)
Hutchinson BG,
et al (1999)
Christenson (2001)
Wagner (2003)
Córcoles AV et al
(2005)
Lamontagne F et al
(2008)
Huss A et al (2009)
88
-- Elderly aged >60 yr with comorbidity g
pneumonia risk i in vaccinated group
(OR=0.41)
-- 59% protective efficacy
p/CI
p<0.05
-- Pneumonia vaccine provides great benefit to
elderly (77% protective efficacy)
Meta-analysis on 13
double-blind trials and
double-blind quasi
experimental studies
-- Effectiveness of 83%
--i risk for pneumonia infection as much as 73%
-- Lower efficacy was not statistically significant
-- It requires 2520 vaccination in the elderly to
prevent one bacteremia annually
-- Prospective
-- n = 100.242 elderly
subjects
-- 841 pneumonia vaccine, 76,117 had received
both influenza and pneumonia vaccine
-- The incidence of pneumonia:
-- Pneumonia vaccine group decrease to 29%
-- Invasive pneumococcal disease decrease
52%
-- Case control
-- 359 cases
-- 718 controls
Mercola (2003)
Christenson (2004)
Results
In subjects receiving vaccination:
-- Pneumonia risk i (OR=0.279)
-- Mortality risk i (OR=0.331)
CI : 24;34
CI : 1;77
p<0.0001
There were no correlation between pneumonia
vaccination lower risk of pneumonia
-- Interventional
prospective
-- 124,702 subjects
receiving influenza/
pneumonia vaccination
-- 134,045 controls
Cohort interventional
11,241 elderly subjects
-- Hospital-based case
control
-- n=43,209 adults with
MCI risk; 999 subjects
with MCI, 3996 controls
-- Meta-analysis on 22
trials, either doubleblind or non-blind trials
-- n = 101,507
-- 23-valent vaccines
were used in 8 studies.
-- Risk of hospitalization related to IPD and
pneumonia in the vaccinated group was i
(OR=0.67 vs OR=0.79)
-- Mortality risk in influenza vaccinated subjects
was i (OR=0.88)
-- Mortality risk in the group receiving two or more
was i (OR=0.65)
-- Length of hospitalization was i
CI : 0.55;0.82
-- Vaccination lowered mortality risk due to
pneumonia
-- Vaccination did not lower hospitalization risk or
the incidence of pneumonia
HR 0.28
p<0.018
HR 0.80
CI : 0.5-1.28
-- Greater number of MCI cases in nonvaccinated adults than the control
OR 0.53
CI : 0.40-0.70
p<0.001
OR 0.33
CI : 0.20-0.46
p<0.001
-- Stronger association in adults with
pneumococcal vaccination >2 years
Pneumococcal vaccination was less effective in
pneumonia prevention strategy:
-- The efficacy against pneumococcal pneumonia
was low, but it was statistically not significant
-- The relative risk for high mortality was high, but
it was statistically not significant
-- Vaccination was not effective in pneumonia
prevention strategies at any causes
CI : 0.75;0.84
CI : 0.69;1.11
CI : 0.54;0.78
RR 1.04; p>0.1
RR 1.00; p>0.1
RR 0.99;
p<0.001
Vol 44 • Number 1 • January 2012
National Consensus on Geriatric Immunization 2011
pneumococcal vaccination). Fever (37.50C) was
found in 10 subjects with influenza vaccination
and there were more subjects who had received
influenza and pneumococcal vaccination (24
subjects) who had fever. In conclusion, double
immunization resulted in more localized side
effects and fever; however the side effects
are typically mild and will resolved without
treatment.
antigenic configuration changes each year (based
on the prevalent strain isolate of the one previous
year). Split virus vaccine is administered since it
is less immunogenic and has fewer side effects.
INFLUENZA VACCINATION PROTOCOL
Indication
Elderly (age > 60 years)
Contraindication
History of hypersensitivity/ allergic response
to eggs and/ or thimerosal.
Side Effects
Skin reaction (localized) such as local
tenderness which occurs in 24 hours after
injection; it is usually well-tolerated and resolved
without any treatment in 2-3 days.
Systemic side effects include fever, malaise,
headache, myalgia, and arthralgia that may occur
in 6 – 12 hours following vaccination and will be
resolved in one to two days.
Hypersensitivity reaction may occur in
individuals who Individuals who have had
allergic responses to egg.
Managing Side Effects
When necessary, 500 mg paracetamol could
be administered to reduce localized tenderness,
fever, headache, myalgia and arthralgia. In severe
hypersensitivity reaction, airway maintenance
and cardiopulmonary resuscitation procedure
should be performed according to the protocol.
Introducing intravenous line (opening access
to the vein) and subcutaneous or intramuscular
epinephrine injection at dose of 0.2 – 1.0 ml
and 200 mg of intravenous hydrocortisone
injection in 30 seconds or methylprednisolone
62.5 – 125 mg (IM or IV in 30 minutes) could
be administered as initial therapy in conjunction
with resuscitation.
Virus Strain; Vaccine Type
The vaccine contains two different strains of
influenza subtype A and one strain of influenza
subtype B. Duration of protection is 1 year. The
vaccine uses inactivated virus based on data of
circulating virus in previous year since the type or
Posology
Suspension for injection; 0.5 mL vial.
Protocol
0.5 mL by subcutaneous or intramuscular
injection; once a year.
PNEUMONIA VACCINE PROTOCOL
Indication
Healthy elderly subject (> 65 years old),
especially those who lived in nursing homes.
The elderly who requires repeated vaccination
are only individuals with impaired immunity
(patients with diabetes, chronic renal failure and
chronic liver disease) and individuals who have
comorbidities or those who had received their
first vaccination at the age less than 65 years.
Contraindication
History of allergy/hypersensitivity to the
vaccine component(s).
Side Effects
Local skin redness, without tenderness or
fever.
Managing Side Effects
500 mg paracetamol could be administered
to reduce localized tenderness or fever.
More severe hypersensitivity reaction needs
airway maintenance and cardiopulmonary
resuscitation procedure according to the protocol.
Introducing intravenous line (opening access
to the vein) and subcutaneous or intramuscular
epinephrine injection at dose of 0.2 – 1.0 ml
and 200 mg of intravenous hydrocortisone
injection in 30 seconds or methylprednisolone
62.5 – 125 mg (IM or IV in 30 minutes) could
be administered as initial therapy in conjunction
with resuscitation.
Vaccine Type
The available vaccine is Pneumo 23, which
is purified polysaccharides of 23 serotype of
Streptococcus pneumonia.
Posology
Solution for injection in a prefilled syringe (0.5
ml).
89
The Indonesian Society of Medical Gerontology
Protocol
Following aseptic and antiseptic procedure,
the vaccine can be given subcutaneously
or intramuscularly in the deltoid region.
Pneumococcal vaccination can be given during
the early influenza epidemic rather than before
influenza season. Booster is not recommended
for the elderly. Pneumococcal and influenza
vaccination can be given together at the same
day, but at different site of injection.
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