ANTIVIRAL TREATMENTS FOR EXISTING INFECTION AVIAN INFLUENZA
Two specific antiviral drugs are now available for the treatment of estab-
Epidemics of influenza among poultry flocks in Asia have made headline
lished influenza infection. Zanamivir (‘Relenza’) and oseltamivir (‘Tamiflu’)
news, but the implications for human infection are still uncertain. Influenza
both interfere with the access of influenza A and influenza B virus into cells
A is fundamentally a virus of birds, with infection of humans and the
and the escape of virus from cells. Zanamivir is administered as a twice
establishment of distinct and self-perpetuating human strains an incidental
daily inhalation to adults and children aged five years and over. Oseltamivir
occurrence, according to Alan Hampson. Influenza A has 16 H (haemag-
is administered as a twice daily capsule to those aged 13 years and over
glutinin) types and nine N (neuraminidase) types. Only three H types (H1,
and as a suspension formulation for children one year and older, and adult
H2 and H3) and three N types (N1, N2, N8) have been known to occur as
patients who cannot swallow capsules.
Dr Dominic Dwyer, medical virologist at Westmead Hospital in Sydney,
Recent outbreaks originating in Asian countries have involved an H5N1
said the drugs are effective for laboratory-confirmed influenza infection,
type, and human infections and deaths have been reported. “The concern
reducing the severity and duration of infection.9,10 “Both treatments need
is that the virus will adapt to the human host, either through mutation
to be commenced within 36-48 hours of the first symptoms, and they
or genetic reassortment by mixing with a human strain,” Mr Hampson
are not effective against other viruses such as RSV, adenovirus, parain-
said. “This type of antigenic shift is the basis of influenza pandemics.” A
fluenza and metapneumovirus which can cause similar symptoms,” Dr
vaccine seed virus has been produced by the UK. This is a Vietnamese
Dwyer said. “We need to educate patients about the need to seek early
strain of the H5N1. Trials testing this vaccine strain have commenced in
treatment, rather than just spending the first few days at home in bed.”
the USA and Australia will also trial vaccines using this same strain. A concern is that if the virus changes considerably in adapting to humans
Most trials of zanamivir and oseltamivir have been in relatively healthy
that this vaccine may no longer be immunogenic.
people. Effects in reducing the duration of illness are more pronounced in people with additional risk factors.
The ongoing spread of the Avian influenza into Mongolia and Russia continues to heighten the threat that a pandemic may result. WHO is
PLANNING VACCINES FOR THE INFLUENZA SEASON
sponsoring the effort to prepare and coordinate an international response.
The formulation of influenza vaccines for Australians is based on
INFLUENZA SPECIALIST GROUP
information from an international surveil ance and monitoring program
The Influenza Specialist Group consists of medical and scientific specialists
A guide for occupational health professionals
coordinated by the World Health Organization. Four Col aborating Centres for Influenza, in Atlanta, London, Melbourne and Tokyo,
as well as professional and patient groups from around the country. It
integrate information from 110 centres in 80 different countries. Mr Alan
cooperates with state and federal governments in educational activi-
Hampson, Convener of the ISG, said the network meets twice yearly
ties about influenza. In conjunction with other organisations including
Vaccination against influenza safely and effectively reduces RISKS OF InFLUEnZA And
to make recommendations for vaccines for the fol owing Northern and
the Australian Medical Association, Royal Australian College of General
the risk of infection, and treatments are now available to BEnEFITS OF VACCInATIOn
Practitioners, WHO Collaborating Centre for Reference and Research on Influenza, Pharmaceutical Society of Australia, National Asthma Council,
al eviate the duration and severity of symptoms if infection
“Influenza is a ‘moving target’ for vaccines,” Mr Hampson said.
Diabetes Australia and the National Heart Foundation it runs the annual
occurs. Although Australia has made excel ent progress in
Influenza is a potentially fatal disease, and a number
“Continuing antigenic drift, which is an evolutionary response by this
Influenza Awareness Program. The Program, launched in 1992, informs
targeting those aged 65 and older, the majority of younger
of studies have shown that deaths directly attributed
easily-mutated RNA virus to host immunity, means that we have
key audiences about the consequences of influenza and the importance of
at-risk individuals - including many who are active in the
to the infection are a substantial under-estimate
to make a prediction each year about the strains that wil be most
workforce - remain unprotected. This publication, from
of the true mortality. A Dutch study, for example,
the Influenza Specialist Group, reviews current issues in
estimated the mortality rate was four times higher
Recommendations from WHO are taken to the Australian Influenza
the prevention and treatment of influenza - at a time when
than that recorded in death certificates, with many
Published by the Influenza Specialist Group
deaths attributed to secondary cardiovascular
Vaccine Committee, within the Therapeutic Goods Administration, in
awareness of viral respiratory infections has been heightened and respiratory complications.1 An actuarial study
October each year for approval and implementation, allowing manufacture
21-31 Goodwood Street, Richmond VIC 3121
by the occurrence of SARS and the recent spread of avian
in Australia suggested the death rate could be
of vaccines to commence. Vaccines normally contain two influenza A
influenza, originating in South-East Asia, highlighting the
eight times higher than that officially recorded.2 In
strains and one influenza B strain, and are developed from clearly-charac-
threat of a potential worldwide pandemic.
addition, while people 65 years and older are at high
terised laboratory stocks of the virus.
risk, nearly a quarter of all deaths occur in younger age groups (Table 1).
1. Sprenger MJW et al. Impact of influenza on mortality in relation to age and underlying disease, 1967-1989. International Journal of Epidemiology
An Australian study estimated that influenza was
responsible for a million medical consultations,
2. De Ravin JW, Gerrard PN. The ef ect of influenza on Australian mortality. Annual Transactions of the Australian Institute of Actuaries 1984; 471-479.
Australian vaccination rates: good progress but room for improvement
20,000-40,000 hospitalisations, 1,500 deaths and
3. Mil s, J. and Yapp, T. An economic evaluation of three CSIRO manufacturing research projects. 1996. Australia, CSIRO.
1.5 million days off work each year, and a total
Health authorities support vaccination in chronic illness
economic cost of about $600 million annually.3
4. Gross A et al. The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Annals of Internal Medicine 1995;
5. Nichol KL. Cost-benefit analysis of a strategy to vaccinate healthy working adults against influenza. Annals of Internal Medicine 2001; 161: 749-759.
Influenza vaccination is about 70% effective against
6. Cohen et al. J Occup Health Safety 19(2): 2003; 167-182.
Implementing a workplace influenza vaccination program
laboratory-proven, symptomatic disease, according
7. Nichol KL et al. The ef ectiveness of vaccination against influenza in healthy, working adults. New England Journal of Medicine 1995; 333: 889-893.
to Dr Heath Kelly, Head of the Epidemiology Unit
8. Lee PY et al. Economic analysis of influenza vaccination and antiviral treatment for healthy working adults. Annals of Internal Medicine 2002; 137:
Antiviral treatments for existing infection
at the Victorian Infectious Diseases Reference
Planning vaccines for the influenza season
Laboratory. “There are special difficulties in
9. Hayden FG et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenza virus infections. GG167 Influenza Study Group. New England Journal of Medicine 1997; 337: 874-880.
assessing the effectiveness of influenza vaccination
in ‘real world’ settings, and data from studies need
10. Hayden FG et al. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: Randomized control ed trials for prevention and treatment. JAMA 1999; 282: 1240-1246.
careful interpretation,” Dr Kelly said. Vaccinations against other viral infections such as measles
are targeted at a stable virus, while the match between the vaccine
Table 1: Estimated influenza deaths in the United Kingdom - 10 year period
department visits or hospital admission, or requires treatment with high
In one Australian company, vaccination benefits were calculated to be
and circulating strains of influenza virus is not always perfect. In
doses of inhaled corticosteroids or oral corticosteroids,” Ms Whorlow
over two and a half times the cost of the program.6 This finding is also
addition, only about 40% of ‘influenza-like’ respiratory viral infections,
said. “There are a number of myths about influenza vaccination in people
supported by international studies, with cost savings estimated at an
characterised by rapid onset, fever and malaise, are in fact caused by
with asthma. It does not trigger asthma attacks, although it may cause
average of $US47 for every person vaccinated in a study published in
a slight increase in symptoms in a minority of people. If this occurs, then
it’s appropriate to increase the use of a preventer medication in line
A number of analyses have addressed specific outcomes, and identified
Table 2: Efficacy of influenza vaccination in preventing outcomes in elderly patients5
with the individual’s written asthma management plan. Most people,
The benefit of workplace vaccination cannot be predicted each year,
pronounced benefits in terms of proven influenza infection: Table 2
though, notice no difference in their asthma symptoms after influenza
as it is influenced by the extent and virulence of the epidemic. A
provides a representative example. In the frail elderly and those with
recent review8 suggests employers need to make individual decisions
underlying conditions, prevention of hospitalisation and death may be
on whether to implement a workplace influenza vaccination based on
the main aim, while in younger healthy people the focus may be on
The National Heart Foundation also encourages people with a range
decreasing time off work or reducing complications from pre-existing
of cardiovascular diseases to have an annual influenza vaccination.
“It’s been estimated that up to two-thirds of people hospitalised
the ease of organising a vaccination program
with influenza are younger than 65 and have conditions such as heart
Contraindications to vaccination include hypersensitivity to the vaccine
disease, lung disease or diabetes,” according to Dr Andrew Boyden,
components and current febrile illness. HEALTH AUTHORITIES SUPPORT
the Foundation’s Medical Affairs Manager. “Although this group suffers
the potential impact of an epidemic.
a significant proportion of the total burden of the disease, only about
AUSTRALIAn VACCInATIOn RATES: VACCInATIOn In CHROnIC ILLnESS
40% of Australians aged between 40 and 65 who have such high-risk
“In organisations where delivery of the vaccine is relatively easy and
GOOd PROGRESS BUT ROOM FOR
Representatives of three leading health authorities have supported
conditions are protected through immunisation.” An acute influenza
sudden rises in absence would be catastrophic, the cost-benefit
IMPROVEMEnT
the benefits of influenza vaccination in people with an underlying
infection predisposed people with heart disease not just to a higher
equation may favour vaccination,” the review stated. “Alternatively,
chronic illness that increases their vulnerability to the infection and its
risk of respiratory complications, but also risked exacerbating their
where vaccine delivery is logistically difficult (for example, wide geographical spread, multiple bases) and the impact of an epidemic
Dr Rosemary Lester, Manager of the Prevention and Perinatal Health
on productivity would be less severe, the case for vaccination is not
Section at the Department of Human Services in Victoria, said there has
Greg Johnson, Chief Executive Officer of Diabetes Australia in Victoria,
as strong.” In health and social care settings, the risk of transmission
been good progress in vaccinating older Australians against influenza
noted that NHMRC guidelines recommend vaccination for adults and
from employees to clients, and vice versa, also needs to be taken into
but room for significant improvement in protecting younger people
children older than 6 months who have chronic illnesses that require
regular medical follow-up. This includes diabetes. “We believe all
“There is no vaccination register for influenza, but vaccination rates
people with diabetes, regardless of their age, should be aware of this
IMPLEMEnTInG A WORKPLACE
in Australians over 65s are fairly stable with latest research from the
recommendation and discuss their individual needs with their doctors,”
AIHW demonstrating uptake rates of 79% in this group,” Dr Lester said.
Mr Johnson said. “Diabetes is a rapidly growing problem, affecting
Only about 40% of InFLUEnZA VACCInATIOn PROGRAM
Australians of al ages. Influenza can exacerbate the problems of
Australians aged
The NHMRC recommends vaccination in adults and children older than 6
diabetes, and it is sensible to take steps to avoid it.”
Influenza vaccination programs have been implemented successfully in
months with chronic pulmonary or circulatory disease, including severe
workplaces for many years, according to Dr Brandon Carp, managing
between 40 and 65
asthma, and other chronic illness that required regular medical follow-up
The NHMRC also recommends vaccination for people with severe
director of the Unified Healthcare Group. “Each program should be
who have such high-
or hospitalisation in the preceding year. In these at risk groups, latest
asthma. Kristine Whorlow, Chief Executive Officer of the National
individualised, with the promotion to staff, the arrangements for funding
research has shown that only 42% of people are getting vaccinated
Asthma Council, said the effects of influenza and the risks of
and other issues being determined according to the circumstances,” he
risk conditions are
complications could be more problematic in the presence of underlying
said. “The programs are very well received because staff and employers
asthma and other chronic respiratory illnesses. “We define ‘severe’
protected through
both benefit from protecting employees’ health, reducing the risks of
“Influenza vaccination is a proven lifesaver for older people and those at
asthma as asthma which causes persistent or frequent symptoms
transmission in the workplace, and decreasing the time lost from work.”
immunisation.
risk for other reasons,” Dr Lester said.
including night-time asthma, limits physical activity, needs emergency
Employers considering an influenza prevention program should assess it like other investments, accounting for the potential direct savings of reduced sick leave and lost productivity, as well as the indirect
IS IT InFLUEnZA? WORKPLACE VACCInATIOn
advantages of offering a staff benefit.
Influenza vaccination programs now tend to be undertaken by
Some people call any cold or other upper respiratory tract infection ‘the flu’. It’s important to realise that influenza is a specific illness caused by the
Vaccinating healthy working adults against influenza will generate cost
contractors rather than in-house personnel. Consultants are able to
influenza virus. Some of the features of influenza are listed in Table 3.
savings 95% of the time.5 The exact economic outcomes may vary
assist with promotion of the program, education about the health
from year to year, depending on factors such as the illness rate in each
consequences of influenza and information about the efficacy and safety
season, the absenteeism that results, and the hourly rate of pay of
of vaccination. “It is vital that a flu vaccination program is provided
through a professional and comprehensive service using well-trained professionals, that the quality of the vaccines is preserved by following
It has also been demonstrated that vaccination has benefits beyond
strict ‘cold chain’ measures, and that any adverse reactions can be dealt
protecting employees against influenza. A study in healthy employees
aged between 18 and 64 found those who were vaccinated against
Workplace vaccination is an excellent method for protecting younger
Chills, muscle aches, malaise, cough, sore
people with underlying chronic diseases against influenza. “A large
25% fewer episodes of upper respiratory tract illness
proportion of this age group are in the workforce but mightn’t
43% fewer days off work because of upper respiratory illness
necessarily have the opportunity to discuss it with their GP,” Dr Carp
said. “They often view themselves as healthy, and might not be aware
*Note: some other respiratory viruses may cause influenza-like illness
44% fewer visits to doctors because of upper respiratory illness.
of the special advantages of vaccination.”
Problems and Hazards of Induction of Labor The Coalition for Improving Maternity Services (CIMS) is concerned about the dramatic increase andongoing overuse of induction of labor. The U.S. induction rate has more than doubled since 1989, risingfrom one woman in ten to one woman in five in 2001.22 This may, however, grossly undercount the trueincidence of labor induction. Nearly half of wo
AZ44821C_Dzagnidze.qxd:AZ44821 Dzagnidze 1/12/08 17:05 Page 1 CHANGES IN ER BETA VERSUS ER ALPHA IN SHORT-TERM STUDIES OF ANTI-ESTROGEN THERAPIES Giorgi Dzagnidze,1 Andrew R Green,2 Valerie Speirs,3 Henry Zhang,2 Abeer M Shaaban,4 Sally Garnett,5 Ian O Ellis,2 John FR Robertson,6 Justin Lindemann5 1National Oncology Center, Tbilisi, Georgia; 2Division of Pathology, School of Molecular Medical