|
Introduction
The term pandemic refers to a massive worldwide accumulation of illnesses
with a high infection rate and mortality, triggered by a new subtype
of virus against which most of the population is not immune (not protected
by past infections or vaccinations). In the 20th century, influenza
caused three pandemics with serious consequences. In 1918-20 the "Spanish
flu" (influenza A (H1N1)) resulted in 20-50 million deaths around
the world. In 1957-60 the Asian flu (influenza A (H2N2)) and in 1968-70
the Hong Kong flu (influenza A (H3N2)) each accounted for about 1 million
deaths. The course of the Russian flu (influenza A (H1N1)) in 1977-8
was significantly milder.
It is currently not possible to forecast reliably whether
an influenza pandemic will occur next year or in 2, 20, or 30 years,
or what the extent of the morbidity and mortality of the outbreak will
be. The World Health ‰ ‰ Organization (WHO) and most experts
expect an influenza pandemic in the foreseeable future (1).
It would be dangerous to rely merely on a talent for
improvisation and not plan for a pandemic. All of the available options
and actions that could be taken in the event of a pandemic must be meticulously
assessed and all possible support systems employed to avoid mass panic
and prevent an even greater threat to public order. A practical social
consensus with regard to damage prevention and disaster preparedness
plans is indispensable. The expected damage must be socially controlled
to limit the effects to tolerable levels (2).
Scenarios and possible action
It is decisive for the course of a pandemic and the extent of its socio-economic
effects whether, when, and to what extent a vaccine is available, and
whether and when a suitable virostatic agent is available for pre- or
post-exposure chemoprophylaxis or treatment. The best way to influence
the course of a pandemic would still be an early subtype specific influenza
vaccination of a maximum number of exposed people. New studies have
shown that supplying the population with newly developed virostatic
agents could become important in the future (3). These would also have
to be provided for the segment of the vaccinated population that could
fall seriously ill despite being immunised.
A functional preparedness plan initially assumes a
worst case scenario. On the basis of the key data from the pandemic
of 1918-20 (4), we propose the following situation with respect to the
current population of Germany: 20 to 25 million cases of influenza,
200 000 admissions to hospital with a total of 1.6 million days' hospitalisation,
120 000 deaths from influenza, and an annual excess mortality of 175
000. About 1.2 million cases of pneumonia as a secondary infection should
also be expected.
Objectives of the pandemic preparedness plan
- the objectives of the pandemic preparedness plan for Germany would
be:
- the structuring of the organisational actions;
- the analysis of actions that can be taken and ensuring good preparation;
- and a starting position in advance so that as few people as possible
would have their health impaired and life threatened.
Mortality and morbidity from viral influenza must be
kept as low possible by preventive medicine or hygienic, antiepidemic,
and therapeutic measures. This can be achieved by:
a) developing a satisfactory immunity among a large part of the population
by preventive vaccinations;
b) epidemic hygienic interventions such as preventive protection against
infection;
c) dispensing timely and appropriate pre- and post-exposure prophylaxis,
and
d) providing medical care for people who are already ill to minimise
deaths and late complications.
Depending on the extent of the morbidity resulting
from a pandemic, these health impairments are not the only consequences
that should be expected. For example, most of the aforementioned measures
cannot be implemented if too few trained personnel are available. Furthermore,
essential services - such as the supply of water, energy, food, communications,
public transport, and internal and external security - that may be endangered
by pandemic related personnel losses must be guaranteed (5).
Vaccination
Currently, the delay between the identification of a new influenza virus
subtype and the release of the first vaccine dosages would be at least
three months and closer to six to eight months. It is unlikely that
such ample warning time would be given in the event of a pandemic. There
may be no vaccine available in the first year of a pandemic, and one
would have to rely exclusively on antiviral agents and antiepidemic
measures.
The two vaccine producing companies in Germany would be able to manufacture
a total of 3-4 million doses of a monovalent subunit vaccine (15 g antigen/vaccine
dosage) within three months after receiving a suitable seed virus, not
considering the current regulations that ask for approved clinical studies.
The fact that both manufacturers are subsidiaries of foreign companies
and regularly sell only around a quarter of their total vaccine production
in Germany also needs to be taken into consideration. In the event of
a pandemic, it would be difficult to expect these companies to provide
a greater proportion of their production for the German vaccination
programme unless agreements had been made in advance. In a future Europe,
national solutions should be replaced by a European solution. A maximum
of 750 000-1 million doses would be available. For each additional week,
an additional 3-4 million doses could be produced and 750 000-1 million
distributed in Germany, so 4-5 million doses could be expected after
four months, seven to 10 million after five months, and not more than
10-14 million after six months. Even after a year, the number of available
doses for a single vaccination would be enough for only half of Germany's
population. In addition, during the second wave, a variant of the subtype
causing the pandemic could occur due to antigen drift, which means that
the vaccine would have to be modified. An increase in the number of
available vaccine doses by a factor of 1.5 would result if a cleaned,
inactivated full virus could be licensed and used as a vaccine as an
alternative to the highly refined subunit vaccine (5). If current trends
in vaccine development (reducing the quantity of antigens and using
highly effective adjuvants) are successful, the number of vaccine doses
produced in the same period of time could be considerably higher. But
adjuvated vaccines must have been previously licensed and evaluated
before extensive use.
If there is a shortage of vaccines and antiviral medication,
decisions will have to be made about who receives priority treatment.
Three different principles should serve as the basis for a list of priority
groups.
- The sociopolitical aspect of securing medical care and public order
as a priority (preferred vaccination and treatment of medical personnel,
firemen, policemen, those employed by energy and water utility companies,
etc).
- The specific individual medical aspects with regard to the priority
treatment of risk groups (elderly and chronically ill people and,
possibly, infants and very young children - those parts of the population
deemed to be especially at risk with regard to mortality as a result
of contracting an influenza infection).
- The epidemiological aspect - the vaccination and medical treatment
of those for whom infection is high because of lifestyle or employment,
and those who are likely to pass on the illness (infants, students,
people working in institutions with a high exposure to the public:
medical staff, teachers, public offices).
Even considering the situation solely with regard to
maintaining medical treatment facilities and personnel and the most
urgently required infrastructure, more than 7 million people in Germany
would need to be given priority treatment and receive vaccines and chemotherapeutic
agents. In accordance with the current recommendations made by the Ständige
Impfkommission (STIKO, permanent immunisation committee), an additional
26 million older and chronically ill people would also need to be vaccinated.
But only 12 million dosages of influenza vaccine are currently sold
during interpandemic periods in Germany. This proves that influenza
vaccination even among that segment of the population for which it is
routinely recommended is not common. But as this figure fundamentally
determines the production capacity of influenza vaccine also during
pandemic periods, an increase in the number of vaccinations provided
during interpandemic periods could improve the availability of a vaccine
in the event of a pandemic.
What is currently not clear is whether a single dose
of vaccine would provide sufficient protection against a new subtype
or whether several administrations are necessary. Complete immunisation
of the entire population will not be possible during a pandemic; a decision
therefore has to be made about whether most of the population should
be provided with limited protection by receiving a single vaccine dose
or whether a booster should be administered to provide fewer people
with full protection. During a pandemic it will be difficult to keep
records of those people who are to be offered a second dose. An additional
unsolved problem is the cost of the vaccine and vaccination itself,
and of liability if a new vaccine has unexpected side effects.
Chemoprophylaxis and antiviral treatment
Initial clinical studies have shown that, compared with the M2 inhibitors
(amantadine and rimantadine) the neuraminidase inhibitors (NI) have
increased effectiveness, fewer side effects, and reduced development
of resistance. NI resistant strains, which rarely manifested themselves
in the past, were non-virulent, in contrast to amantadine resistant
strains. They also provide immediate protection to a local influenza
outbreak and can close the gap until an appropriate protective vaccination
takes effect. The rate of prophylactic effectiveness for the two NIs
currently on the market amounts to 60-90% (6-10). But the ready to use
medication has a low stability (two to three years); when stockpiling,
preliminary production stages must be stored. These should be processed
into the end product in the event of a pandemic. According to the manufacturers'
information, a maximum of 500 000 packages of the medication could be
produced on a daily basis, assuming that the basic ingredients are available
(11). In comparison, non-confirmed statements have been made to the
effect that the M2 inhibitors have an extraordinary chemical and thermal
stability of up to 25 years or longer (12). The price advantage provided
by amantadine would no longer be a valid argument if satisfactory effectiveness
drops off as a result of resistance. When considering the amount required
in a pandemic situation, a primary use of amantadine or rimantadine
would still be an option that is not (yet) possible to ignore (13).
Protection from secondary infections (pneumonia)
If sufficient suitable influenza vaccines and virostatics are not available
at the time of a pandemic outbreak, it is still possible to prevent
at least the outbreak of two of the most feared secondary infections
that accompany influenza: pneumococcal pneumonia or meningitis, and
illnesses resulting from Haemophilus influenzae. The objective
here must be the full vaccination of the high risk groups during the
interpandemic phase. According to the recommendations concerning the
vaccination against influenza, STIKO recommends that all persons older
than 60 and those at an increased risk because of poor health should
be vaccinated against pneumococcal infections (14). This also raises
the question of storing the vaccine before a pandemic occurs as long
as pneumococcal vaccination is not recommended for all age groups. This
also applies to antibiotics, antipyretic agents, and other drugs for
which there will be a much higher demand during a pandemic (15).
Protection from exposure and antiepidemic measures
If a pandemic begins, information sheets will be used to inform the
population on how to protect themselves against exposure: rooms should
be thoroughly ventilated, handshaking should be avoided, tissues used
and disposed of properly, etc. People who are in frequent and close
contact with others can reduce the risk of infection by wearing a gauze
mask, for example. A ban on visits to medical and nursing facilities
could also be considered. Patients with acute respiratory symptoms need
to be separated early from those with other non-infectious illnesses
in the admission and waiting areas of outpatient and inpatient facilities.
In private practices it may also be possible to arrange separate treatment
times for the two groups. This should be considered when elaborating
hygiene plans.
The effectiveness of measures such as the closing of schools and other
communal facilities, a ban on public events or large crowds, and the
isolation of infected persons and suspected cases, where appropriate,
have not been examined in detail with regard to influenza. Therefore,
their application in special situations can be ordered only on trial.
The same applies to the enforcing of border controls, restrictions on
international traffic and immigration, etc, whose practicality and socioeconomic
consequences are difficult to calculate in the face of increased globalisation.
Surveillance
The constantly changing composition of influenza viruses necessitates
detailed knowledge about the circulating strains. An international network
has been created by WHO to gather these data. It consists of 110 national
and four global WHO collaborating centres. In Germany, influenza surveillance
is implemented by the Arbeitsgemeinschaft Influenza (AGI, influenza
working group), the Robert Koch-Institut, and the national reference
centre for influenza. Weekly reports cover influenza activity and the
number of specimens isolated by type and subtype. The circulating viruses
are typed serologically by the national centres, and a selection of
representative strains is sent rapidly to the WHO collaborating centres
for further identification of strains (16). This way a potentially pandemic
virus can be detected very quickly.
Outlook
By forming an official influenza pandemic planning working group, the
German health ministry, the Robert Koch-Institut as the supreme federal
authority responsible for infection prevention, and the states, which
discussed this subject at their health ministers' conference in June
2001, have underlined their common aim of counteracting the potential
threat to the health of the general population with foresight. In this
way, they are also responding to the WHO recommendation that all countries
should develop a national pandemic preparedness plan.
All countries should consider their national preparedness
as a pandemic will affect everyone. Nevertheless, a broader view might
be helpful when it comes to decisions on priorities for vaccination
and chemoprophylaxis, vaccine production, storage of antiviral drugs,
and implementation
of antiepidemic measures. Common solutions at a European level are necessary.
|