Vogelgrippe H5N1 - Behandlung oder Prophylaxe ?
Verfasst: Do 12. Jun 2008, 19:10
AVIAN INFLUENZA, HUMAN (52): TREATMENT OR PROPHYLAXIS
*****************************************************
A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>
Date: Tue 10 Jun 2008
Source: HSToday online [abbreviated and edited]
<http://hstoday.us/content/view/3741/150>
The US government's new proposal to use drugs like Tamiflu and Relenza
[oseltamivir and zanamivir; neuraminidase inhibitors] as a prophylaxis to
prevent infection by a pandemic strain of influenza is wrongheaded, says Dr
Graeme Laver, a former professor of biochemistry and molecular biology in
the John Curtin School of Medical Research at the Australian National
University in Canberra. Laver told HSToday.us that "prophylaxis with
Tamiflu in a pandemic is wrong. Early treatment is the only way to go."
But the US government proposes to use Tamiflu and Relenza prophylactically
to prevent infection, including giving guidelines to businesses that may
want to buy the drugs in advance to treat or protect employees. The
Department of Health and Human Services' (HSS) pandemic plan calls for
"targeted antiviral prophylaxis ... of disease clusters, administration of
antiviral treatment to persons with confirmed or suspected cases of
pandemic influenza, and provision of drug prophylaxis to all persons in
[an] affected community."
Similarly, should clusters of humans be found infected with a virulent
strain of influenza like H5N1, the World Health Organization's plan of
attack is to flood the regions with Tamiflu in the hope that it will quell
further spread of the virus. Dr. Ben Schwartz, a pandemic planner at HHS
who wrote most of the new guidelines, told Reuters that "for prophylaxis of
health care and emergency services workers, the responsibility for
purchasing and stockpiling the drugs would primarily be on the health care
organizations ... or on the emergency organizations that would be
protecting their workforce."
Meanwhile, HSToday has learned that there also are discussions within HHS
about making Tamiflu and Relenza "push packets" available to people to have
on hand in the event of a pandemic. Laver also has problems with that
notion. "Personal stockpiles of Tamiflu or Relenza are not a good idea,"
Laver told HSToday, explaining, "personal stockpiles are wrong for 2
reasons. First, nothing might happen, and the stockpiles will be wasted,
and, 2nd, if the stockpiles are used, it will be on the basis of
self-diagnosis, and that is not a great idea."
"Widespread prophylaxis to control a pandemic before any vaccine is
available, is totally wrong," Laver continued. "It would be a wicked waste
of a valuable resource! Australia had a policy (long since abandoned) to
provide essential workers with Tamiflu prophylaxis for 6 weeks at the start
of the pandemic." But "what happens then?" Laver mussed. "Apart from the
difficulty in identifying the essential workers and keeping the Tamiflu
stockpile safe from desperate people who would do anything to get the drug,
at the end of 6 weeks, all those people who had been taking Tamiflu for
prophylaxis would be left without protection. And the stockpile would have
vanished."
Laver explained to HSToday that it is "much better to use Tamiflu only for
early treatment. If people with flu symptoms take Tamiflu immediately, say
within 6 or so hours after symptom onset, the infection should be rapidly
terminated, the person should recover, and then, and this is important,
should then be immune to reinfection for the rest of the pandemic. Much
better than any vaccine. This has been called 'Aborted-infection
Immunization,' and to use Tamiflu in this way would allow many health care
workers and so on to go about their business without fear of reinfection."
"People will, of course, say, 'but aborted-infection immunization has never
been shown to work,'" Laver said. "Of course not, but then neither has
long-term prophylaxis or the use of pre-pandemic vaccines. But my bet is
that it will!" To work, Tamiflu must be taken in proper doses within 6 to
12 hours after onset of symptoms. "48 hours is about the limit the drug is
effective," Laver said. Laver does believe that "prophylaxis with Tamiflu
should be used in some circumstances. For example, Tamiflu should be taken
by poultry workers culling H5 or H7 infected chickens," he said.
Prior to HHS's release of its new proposals Laver expressed his concerns in
a letter to Dr Bruce Gellin, director of the department's National Vaccine
Program Office and chairman of HHS secretary Michael Leavitt's Task Force
on Influenza Preparedness. "I believe this is completely wrong," Laver
wrote Gellin, explaining that "as soon as prophylaxis is stopped, the
person taking Tamiflu is just as susceptible to infection as before. Early
treatment would be so much better." Laver told Gellin: "Tamiflu should be
available over-the-counter [OTC] in pharmacies now, where flu victims can
get it without the time-wasting need to 1st get a prescription from a
doctor. There is no need for a prescription, and the time taken to get one
can render Tamiflu pretty well useless. "To have people familiar with the
correct use of Tamiflu (and Relenza) for seasonal influenza infections
would mean the community would be 'trained' in the correct use of these
drugs in the event of a pandemic. I imagine that, in this case, there would
be much less panic than would occur otherwise."
Laver told HSToday that it would be "much better to hold stocks of the
drugs in every pharmacy in the country where it can be got quickly after
diagnosis by a trained pharmacist or other health care worker." Laver also
said "using a rapid flu test to assist this would be a good idea, so that
people who think they have the flu can be properly diagnosed quickly and
take the drugs very soon after symptom onset. This rapid procedure of 'test
and treat' would mean that the infection should be immediately terminated
and the flu victim experience a quick recovery, seems quite simple, really!"
In late 2006, the Centers for Disease Control and Prevention awarded USD
11.4 million in contracts to 4 companies working to develop new diagnostic
tests that doctors and field epidemiologists could eventually use to
quickly and accurately test patients for avian influenza H5N1 and other
emerging influenza viruses, as well as more common [seasonal] influenza
viruses.
Brit Oiulfstad, pandemic influenza coordinator for the County of Los
Angeles, had earlier expressed concern to HSToday about the prophylactic
use of Tamiflu. Oiulfstad said she and other authorities "are concerned
about ... the current push for community-wide antiviral prophylaxis when
the effectiveness for such long-term use (several times the duration of the
recommended treatment period) has not been evaluated." Continuing,
Oiulfstad told HSToday that "planning for antivirals is very complex, as we
are not certain that the current antivirals will be effective in whatever
viral strain will be circulating. However, planning for any pharmaceutical
dispersal is good for other future events.
The Infectious Diseases Society of America (IDSA) said in an October 2005
statement that "personal stockpiling would likely lead to inappropriate use
and wastage," adding, "institutions should not stockpile drug for
prophylaxis of health care workers, as this strategy requires much greater
drug supplies than early treatment, and could deplete the reserve necessary
for treatment on a national level." IDSA and the Society for Healthcare
Epidemiology of America (SHEA) said local health care institutions ought to
have sufficient stockpiles to treat sick people and maintain the health
care system in the event of a pandemic. The group advised health care
facilities to have enough supply of the drugs to reduce hospitalizations
and mortality and maintain social order and function in the event of a
severe pandemic. "Hospitals will need to be able to treat those who are
sick and keep their own doors open," said Dr Kathleen Neuzil, chair of
IDSA's Pandemic Influenza Task Force. IDSA and SHEA do not recommend
institutions stockpile enough drugs to prevent illness among health care
workers because this strategy requires much greater drug supplies than
early treatment and could deplete the reserve necessary for treatment on a
national level.
HHS' goal is to have 81 million doses (10 capsules per dose) of Tamiflu,
Relenza, and Rimantidine available for the US population. Of this 81
million, 50 million are to be stored in the Strategic National Stockpile
(SNS). Of this, about 44 million courses are to be held for emergency
pandemic usage by states and 6 million reserved for domestic containment
efforts at the onset of localized outbreaks. Of the 50 million doses the
government plans to put into the SNS, though, HHS says only 37.4 million
have been procured and 29.8 million treatment courses put into the SNS, and
the remaining 7.6 million treatment courses are due by the end of calendar
year 2007. The balance, HHS says, is expected this year [2008].
The Department of Defense has stockpiled many millions less, and less than
half the states have stockpiled only 13 million of the 31 million doses HHS
is supposed to help states buy, largely because the remaining states have
had difficulty coming up with their share of the money for purchases.
There's another problem with Tamiflu. It has a shelf life of about 5 years,
which means stockpiles must be replenished. Existing mass stockpiles will
have to be replaced in order to ensure there are adequate stores beyond
2010, but according to F Hoffmann-La Roche, new orders for future batches
have dwindled, and there's a lag time in making the drug. The company has,
though, entered into agreements with other countries to allow them to
manufacture Tamiflu themselves.
The Food and Drug Administration manages a Shelf Life Extension Program,
but only products in the federal SNS are eligible to receive an extended
expiration date if a drug meets specific conditions. When states'
stockpiles expire, they will have to buy new supplies without additional
federal assistance. This problem, combined with those states that have yet
to procure their own stockpiles, means there could be a widespread national
shortage of antivirals. Thus, as Laver pointed out, using Tamiflu to treat
rather than trying to prevent infections is necessary to prevent the
valuable stockpiles of these drugs from being wasted.
[byline: Anthony L Kimery]
--
communicated by:
ProMED-mail rapporteur Mary Marshall
[Tamiflu (oseltamivir) and Relenza (zanamivir) are viral neuraminidase
inhibitors that can be used in the treatment of both Influenza A and B
virus infections. These anti-viral agents act as transition-state analogue
inhibitors of the influenza virus neuraminidase, preventing progeny virions
from emerging from infected cells. Tamiflu was the 1st orally active
neuraminidase inhibitor commercially developed. It is a prodrug, which is
hydrolysed in the liver to the active metabolite.
The preceding article argues for restriction of the use of Tamiflu to
treatment of influenza rather than for prophylaxis that currently appears
to be the preferred strategy in pandemic planning. However, the logic of
Graeme Laver's argument for restriction of the use of Tamiflu until
symptoms develop in order to achieve "aborted-infection immunization" is
compelling. - Mod.CP]
*****************************************************
A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>
Date: Tue 10 Jun 2008
Source: HSToday online [abbreviated and edited]
<http://hstoday.us/content/view/3741/150>
The US government's new proposal to use drugs like Tamiflu and Relenza
[oseltamivir and zanamivir; neuraminidase inhibitors] as a prophylaxis to
prevent infection by a pandemic strain of influenza is wrongheaded, says Dr
Graeme Laver, a former professor of biochemistry and molecular biology in
the John Curtin School of Medical Research at the Australian National
University in Canberra. Laver told HSToday.us that "prophylaxis with
Tamiflu in a pandemic is wrong. Early treatment is the only way to go."
But the US government proposes to use Tamiflu and Relenza prophylactically
to prevent infection, including giving guidelines to businesses that may
want to buy the drugs in advance to treat or protect employees. The
Department of Health and Human Services' (HSS) pandemic plan calls for
"targeted antiviral prophylaxis ... of disease clusters, administration of
antiviral treatment to persons with confirmed or suspected cases of
pandemic influenza, and provision of drug prophylaxis to all persons in
[an] affected community."
Similarly, should clusters of humans be found infected with a virulent
strain of influenza like H5N1, the World Health Organization's plan of
attack is to flood the regions with Tamiflu in the hope that it will quell
further spread of the virus. Dr. Ben Schwartz, a pandemic planner at HHS
who wrote most of the new guidelines, told Reuters that "for prophylaxis of
health care and emergency services workers, the responsibility for
purchasing and stockpiling the drugs would primarily be on the health care
organizations ... or on the emergency organizations that would be
protecting their workforce."
Meanwhile, HSToday has learned that there also are discussions within HHS
about making Tamiflu and Relenza "push packets" available to people to have
on hand in the event of a pandemic. Laver also has problems with that
notion. "Personal stockpiles of Tamiflu or Relenza are not a good idea,"
Laver told HSToday, explaining, "personal stockpiles are wrong for 2
reasons. First, nothing might happen, and the stockpiles will be wasted,
and, 2nd, if the stockpiles are used, it will be on the basis of
self-diagnosis, and that is not a great idea."
"Widespread prophylaxis to control a pandemic before any vaccine is
available, is totally wrong," Laver continued. "It would be a wicked waste
of a valuable resource! Australia had a policy (long since abandoned) to
provide essential workers with Tamiflu prophylaxis for 6 weeks at the start
of the pandemic." But "what happens then?" Laver mussed. "Apart from the
difficulty in identifying the essential workers and keeping the Tamiflu
stockpile safe from desperate people who would do anything to get the drug,
at the end of 6 weeks, all those people who had been taking Tamiflu for
prophylaxis would be left without protection. And the stockpile would have
vanished."
Laver explained to HSToday that it is "much better to use Tamiflu only for
early treatment. If people with flu symptoms take Tamiflu immediately, say
within 6 or so hours after symptom onset, the infection should be rapidly
terminated, the person should recover, and then, and this is important,
should then be immune to reinfection for the rest of the pandemic. Much
better than any vaccine. This has been called 'Aborted-infection
Immunization,' and to use Tamiflu in this way would allow many health care
workers and so on to go about their business without fear of reinfection."
"People will, of course, say, 'but aborted-infection immunization has never
been shown to work,'" Laver said. "Of course not, but then neither has
long-term prophylaxis or the use of pre-pandemic vaccines. But my bet is
that it will!" To work, Tamiflu must be taken in proper doses within 6 to
12 hours after onset of symptoms. "48 hours is about the limit the drug is
effective," Laver said. Laver does believe that "prophylaxis with Tamiflu
should be used in some circumstances. For example, Tamiflu should be taken
by poultry workers culling H5 or H7 infected chickens," he said.
Prior to HHS's release of its new proposals Laver expressed his concerns in
a letter to Dr Bruce Gellin, director of the department's National Vaccine
Program Office and chairman of HHS secretary Michael Leavitt's Task Force
on Influenza Preparedness. "I believe this is completely wrong," Laver
wrote Gellin, explaining that "as soon as prophylaxis is stopped, the
person taking Tamiflu is just as susceptible to infection as before. Early
treatment would be so much better." Laver told Gellin: "Tamiflu should be
available over-the-counter [OTC] in pharmacies now, where flu victims can
get it without the time-wasting need to 1st get a prescription from a
doctor. There is no need for a prescription, and the time taken to get one
can render Tamiflu pretty well useless. "To have people familiar with the
correct use of Tamiflu (and Relenza) for seasonal influenza infections
would mean the community would be 'trained' in the correct use of these
drugs in the event of a pandemic. I imagine that, in this case, there would
be much less panic than would occur otherwise."
Laver told HSToday that it would be "much better to hold stocks of the
drugs in every pharmacy in the country where it can be got quickly after
diagnosis by a trained pharmacist or other health care worker." Laver also
said "using a rapid flu test to assist this would be a good idea, so that
people who think they have the flu can be properly diagnosed quickly and
take the drugs very soon after symptom onset. This rapid procedure of 'test
and treat' would mean that the infection should be immediately terminated
and the flu victim experience a quick recovery, seems quite simple, really!"
In late 2006, the Centers for Disease Control and Prevention awarded USD
11.4 million in contracts to 4 companies working to develop new diagnostic
tests that doctors and field epidemiologists could eventually use to
quickly and accurately test patients for avian influenza H5N1 and other
emerging influenza viruses, as well as more common [seasonal] influenza
viruses.
Brit Oiulfstad, pandemic influenza coordinator for the County of Los
Angeles, had earlier expressed concern to HSToday about the prophylactic
use of Tamiflu. Oiulfstad said she and other authorities "are concerned
about ... the current push for community-wide antiviral prophylaxis when
the effectiveness for such long-term use (several times the duration of the
recommended treatment period) has not been evaluated." Continuing,
Oiulfstad told HSToday that "planning for antivirals is very complex, as we
are not certain that the current antivirals will be effective in whatever
viral strain will be circulating. However, planning for any pharmaceutical
dispersal is good for other future events.
The Infectious Diseases Society of America (IDSA) said in an October 2005
statement that "personal stockpiling would likely lead to inappropriate use
and wastage," adding, "institutions should not stockpile drug for
prophylaxis of health care workers, as this strategy requires much greater
drug supplies than early treatment, and could deplete the reserve necessary
for treatment on a national level." IDSA and the Society for Healthcare
Epidemiology of America (SHEA) said local health care institutions ought to
have sufficient stockpiles to treat sick people and maintain the health
care system in the event of a pandemic. The group advised health care
facilities to have enough supply of the drugs to reduce hospitalizations
and mortality and maintain social order and function in the event of a
severe pandemic. "Hospitals will need to be able to treat those who are
sick and keep their own doors open," said Dr Kathleen Neuzil, chair of
IDSA's Pandemic Influenza Task Force. IDSA and SHEA do not recommend
institutions stockpile enough drugs to prevent illness among health care
workers because this strategy requires much greater drug supplies than
early treatment and could deplete the reserve necessary for treatment on a
national level.
HHS' goal is to have 81 million doses (10 capsules per dose) of Tamiflu,
Relenza, and Rimantidine available for the US population. Of this 81
million, 50 million are to be stored in the Strategic National Stockpile
(SNS). Of this, about 44 million courses are to be held for emergency
pandemic usage by states and 6 million reserved for domestic containment
efforts at the onset of localized outbreaks. Of the 50 million doses the
government plans to put into the SNS, though, HHS says only 37.4 million
have been procured and 29.8 million treatment courses put into the SNS, and
the remaining 7.6 million treatment courses are due by the end of calendar
year 2007. The balance, HHS says, is expected this year [2008].
The Department of Defense has stockpiled many millions less, and less than
half the states have stockpiled only 13 million of the 31 million doses HHS
is supposed to help states buy, largely because the remaining states have
had difficulty coming up with their share of the money for purchases.
There's another problem with Tamiflu. It has a shelf life of about 5 years,
which means stockpiles must be replenished. Existing mass stockpiles will
have to be replaced in order to ensure there are adequate stores beyond
2010, but according to F Hoffmann-La Roche, new orders for future batches
have dwindled, and there's a lag time in making the drug. The company has,
though, entered into agreements with other countries to allow them to
manufacture Tamiflu themselves.
The Food and Drug Administration manages a Shelf Life Extension Program,
but only products in the federal SNS are eligible to receive an extended
expiration date if a drug meets specific conditions. When states'
stockpiles expire, they will have to buy new supplies without additional
federal assistance. This problem, combined with those states that have yet
to procure their own stockpiles, means there could be a widespread national
shortage of antivirals. Thus, as Laver pointed out, using Tamiflu to treat
rather than trying to prevent infections is necessary to prevent the
valuable stockpiles of these drugs from being wasted.
[byline: Anthony L Kimery]
--
communicated by:
ProMED-mail rapporteur Mary Marshall
[Tamiflu (oseltamivir) and Relenza (zanamivir) are viral neuraminidase
inhibitors that can be used in the treatment of both Influenza A and B
virus infections. These anti-viral agents act as transition-state analogue
inhibitors of the influenza virus neuraminidase, preventing progeny virions
from emerging from infected cells. Tamiflu was the 1st orally active
neuraminidase inhibitor commercially developed. It is a prodrug, which is
hydrolysed in the liver to the active metabolite.
The preceding article argues for restriction of the use of Tamiflu to
treatment of influenza rather than for prophylaxis that currently appears
to be the preferred strategy in pandemic planning. However, the logic of
Graeme Laver's argument for restriction of the use of Tamiflu until
symptoms develop in order to achieve "aborted-infection immunization" is
compelling. - Mod.CP]