- Hello Jeff:
-
- Monkeypox has been the focus of research for many years.
In 2000, CSIRO in Australia, added the IL 4 gene to monkeypox and found
that this action caused monkeypox to become "weaponized" with
a 100% kill rate. CSIRO scientists claimed that the purpose of the experiment
was to alter monkeypox for use as rodent birth control. Although the experiment
was not successful in as much as rodent birth control, the scientists still
submitted the "unexpected" result a"blueprint" for
weaponzied poxivirus to medical journals for all to see.
-
- Ft. Detrick, as well as other US government and private
labs have also been researching monkeypox.
-
- I do hope that more information will be forthcoming about
the true origin of the US monkeypox outbreak. Once that a pathogen has
emerged, it is very difficult to contain an outbreak and to ensure that
the pathogen does not become ingrained and endemic. I think that it is
going to be very difficult, if not impossible, to purge the US of Monkeypox.
We did not do well with other diseases, such as West Nile Virus, HantaVirus
especially Sin Nombre, SARS etc.
-
- The following website, asmbiodefense.org/tuepos.asp has
many biodefense research article/abstracts, even including work on the
1918 influenza.
-
- Patricia Doyle
-
- http://www.asmbiodefense.org/tuepos.asp
-
- 199
- IV Cidofovir Treatment of Smallpox and Monkeypox in the
Cynomolgus Monkey Model
- J. W. Huggins, S. H. Zwiers, R. O. Baker, L. E. Hensley,
T. Larsen, M. J. Martinez, P. J. Jahrling; USAMRIID, Fort Detrick, MD.
-
- IV Cidofovir (approved for treatment of cytomegalovirus
retinitis in AIDS patients) is available for contingency use to treat cases
of smallpox under IND,s held by both DHHS and DoD. Evidence supporting
IND use is the ability of cidofovir to inhibit Variola (smallpox) and other
orthopoxviruses in vitro and to treat mice lethally infected with cowpox
by either the intranasal or aerosol routes. Aerosol infection of cynomolgus
monkeys with monkeypox produced a lethal fibrinonecrotic bronchopneumonia,
which could be treated with cidofovir by using a treatment regimen that
mimicked human treatment. To determine if a lesional model could be successfully
treated, we used the uniformly lethal intravenous monkeypox model to show
that cidofovir prophylaxis provided complete protection, showed no signs
of illness, and controlled viral replication as measured in blood, while
the placebo-treated animal had >850 lesions and blood viral titers,
measured by quantitative real-time TAQMAN®-MGB PCR, first detectable
on day 3, rising to 107 genomes/ml by day 9 and remaining at high levels
until the primate was enthanized moribund on day 12. Similar studies of
intravenous infection with 108 PFU of the Harper strain of Variola produced
a similar disease with > 250 lesions (WHO category "grave) and
33% mortality (day 11), but increasing the viral challenge dose 10-fold
resulted in a 100% acutely lethal disease (mean time to death 4 days) that
more closely mimicked hemorrhagic smallpox, with viral levels in organs
1,000- to 10,000-fold greater than with 108 PFU. Prophylaxis with IV cidofovir
resulted in protection from lethal disease, with significant reductions
of blood viral levels and lesion counts. We believe the lesional model
of smallpox produced by 108 PFU of Harper strain is the most appropriate
primate model for drug evaluation.
-
- v142
- Real-Time TAQMAN®-MGB PCR Assay of Smallpox, Monkeypox,
and Cowpox Genomes in Blood and Tissues from Experimentally Infected Animals
- S. H. Zwiers, D. Miller, R. O. Baker, D. Kulesh, P. B.
Jahrling, J. W. Huggins; USAMRIID, Fort Detrick, MD.
-
- Following the level of virus in blood can be a useful
tool in disease management, especially in monitoring the success of antiviral
therapy. Primate models of smallpox and monkeypox have provided specimens
appropriate for validating methodology and determining if viral burden,
as reflected by virus levels in blood, are useful in monitoring successful
experimental antiviral therapy with IV cidofovir. Blood of experimentally
infected primates was extracted with the Qiagen QIAamp DNA Mini Kit. Incubating
blood or tissues in AL buffer plus Proteinase K for > 1 h at 56°C
completely inactivated Variola (the virus that causes smallpox) and monkeypox.
Consequently, 4 h incubation was adopted as adequate to safely remove Variola-infected
samples from biocontainment. Quantitative TAQMAN®-MGB PCR with a pan-orthopox
primer/probe set directed against the viral hemagglutinin gene allowed
us to evaluate virus levels of 1000 gene copies per ml of whole blood or
gram of tissue. Virus levels in blood of cynomolgus monkeys experimentally
infected with Variola and monkeypox were significantly reduced in monkeys
successfully treated with cidofovir compared with levels in controls (placebo:
monkeypox > 107 and Variola > 5 x 108 genomes/ml). To understand
how the level of virus in blood correlates with virus levels in tissues,
we used the uniformly lethal intranasal infected cowpox mouse model as
a surrogate to correlate virus in blood and tissues throughout the course
of this lethal infection. Virus was first detectable in blood at 48 h after
infection and peaked at greater than 105 genomes per ml by day 5 postinfection.
Near real-time monitoring of virus levels in blood may allow for rapid
evaluation of the efficacy of antiviral therapy during an initial smallpox
outbreak.
-
- Also, Ken Alibek's research:
-
- 195
- Cytokine-mediated Control of Poxvirus Infection
- G. Liu1, Q. Zhai1, T. G. Voss2, M. Maland3, A. Wu1, J.
Wells4, D. Schaffner1, E. Grene1, T. Robinson1, C. L. Bailey1,5, K. Alibek1,5;
1Advanced Biosystems, Inc., Manassas, VA, 2Southern Research Institute,
Frederick, MD, 3Southern Research Institute, Drederick, MD, 4Southern Research
Institue, Frederick, MD, 5George Mason University, Manassas, VA.
-
- Background: Certain cytokines, particularly interferons
(IFN), are well known for their antiviral effects in various virus infections.
In this report, we demonstrate that IL-15, IFN-â and -ã are
capable of enhancing the extrinsic antiviral activity of cultured murine
macrophage cells. Furthermore, we have adapted a mouse respiratory vaccinia
infection model to evaluate the in vivo antiviral effects of cytokines.
Methods: RAW 264.7 cells were activated with individual cytokines and then
co-cultured with vaccinia virus-infected human 293 cells overnight. The
virus titers in the cocultures were measured by plaque assay. Balb/c mice
were infected intranasally with 8 X LD50 of vaccinia virus (strain WR).
Murine cytokines were administered intranasally for 5 consecutive days,
starting one day before the infection. The animals were observed for signs
of sickness and death for 21 days. Results: Our results indicate that IL-15,
IFN-â and -ã are capable of inducing the inhibition of virus
replication in by-stander cells. Intranasal administration of recombinant
murine IFN-á and IFN-ã resulted in animal survival rates
of 100 and 95%, respectively. In contrast, no mice in untreated control
(placebo) survived the lethal vaccinia challenge. The organ virus titers
in treated mice were 100,000-fold lower than that in placebo. IL-15 provided
slight protection (10% survival). Both innate and adaptive host immune
responses are likely to play significant roles in the IFN-mediated control
of poxvirus replication in mice. Conclusions: Intranasal administration
of IFN-á and IFN-ã provides nearly full protection against
respiratory vaccinia virus infection in mice; therefore, our results have
implications in the utilization of interferon as a prophylactic tool on
a scenario of aerosol orthopoxvirus infection.
-
-
-
-
- http://www.biomedcentral.com/news/20030613/04
-
- June 13, 2003 Previous
-
- Monkeypox in the news
- Scientists at US agencies have been using virus as surrogate
and model for smallpox | By Peg Brickley
-
-
-
- Long before it became the topic of hourly news bulletins,
monkeypox was a virus of interest to US researchers intent on creating
safer smallpox vaccines and treatments. Some hope now that monkeypox's
Western Hemisphere debut will spread the wealth of scientific knowledge
back to central and western Africa, where monkeypox is endemic and sometimes
fatal.
-
- "Monkeypox has not been established as a top-priority
disease, and it should be," said Joel Breman, who chaired the World
Health Organization's monkeypox study committee and is now senior scientist
at the National Institute of Health's John E. Fogarty International Center.
"It should be a higher priority because of its potential for exportation,
number one, and number two, because the natural history of monkeypox remains
unknown even 30 years after its discovery in humans and 45 years from its
first discovery in nonhuman primates."
-
- Labs at the US Army Research Institute for Infectious
Diseases (USAMRIID) and at the National Institutes of Health (NIH) labs
in Maryland use monkeypox as a substitute for smallpox because it is easier
to handle in the laboratory and less likely to spread among humans.
-
- "Our main goal has been to look at therapeutics.
We use monkeypox because it is a BSL-3 [biosafety level 3] agent so we
can use it under slightly less strict conditions in the lab," said
Robert Baker, a USAMRIID virologist.
-
- Science and logistics make monkeypox a good surrogate
for the more lethal pox. "Monkeypox produces a disease in monkeys
and people that is essentially identical to smallpox," Baker told
The Scientist.
-
- Animal models created at USAMRIID are being used to test
therapeutics against smallpox, such as the antiviral cidofovir as well
as safer versions of the smallpox vaccine, such as the modified vaccinia
Ankara (MVA) vaccine, that potentially pose less of a threat to immunocompromised
people.
-
- "There are whole groups of people contraindicated
for vaccination," Baker said. "One of our goals is to find an
option for people who shouldn't be taking the vaccine. In addition, we
are trying to extend the window of protection so we can treat post-exposure."
-
- In collaboration with Donald Smee, research professor
at Utah State University's Institute for Antiviral Research, Army scientists
are developing rodent models to replace the more expensive primate test
subjects for monkeypox. Monkeypox's importation to this country, probably
by way of a giant Gambian rat, was "a total surprise," Smee,
who has published extensively on monkeypox, told The Scientist. And no,
Baker said, prairie dogs were never on the list of candidates to serve
as rodent models. Cotton rats show the most promise, Baker said.
-
- Bernard Moss, chief of the viral disease laboratory at
NIH, is evaluating highly attenuated MVA against primates infected with
monkeypox at USAMRIID. Ongoing work is also looking at recombinant proteins,
Moss said, and he expects to report results before the end of the year.
-
- "The top priority is to control and mute this epidemic
so there aren't more cases," Breman told The Scientist. "This
is a huge opportunity both to look at treatments and possibly prevention,
to look at how the disease will be acquired and spread in an environment
where you can actually do surveillance properly."
-
- Links for this article
- J.G Breman, D.A. Henderson, "Poxvirus dilemmas"monkeypox,
smallpox, and biologic terrorism," New England Journal of Medicine,
339:556-559, August 20, 1998.
- http://content.nejm.org/cgi/content/full/339/8/556
-
- Technical Advisory Group on Human Monkeypox
- http://www.who.int/csr/resources/publications/viral/WHO_CDS_CSR
_APH_99_5/en
-
- John E. Fogarty International Center
- http://www.fic.nih.gov/
-
- US Army Research Institute for Infectious Diseases
- http://www.usamriid.army.mil/
-
- Donald Smee
- http://advs.usu.edu/advs/FACULTY/dsmee.htm
-
- Utah State University Institute for Antiviral Research
- http://www.usu.edu/iar/index.html
-
- D.F. Smee et al., "Characterization of wild-type
and cidofovir-resistant strains of camelpox, cowpox, monkeypox, and vaccinia
viruses." Antimicrobial Agents and Chemotherapy, 46:1329-1335, May
2002.
- http://aac.asm.org/cgi/content/full/46/5/1329?view=full&pmid=11
959564
-
- ©2003, The Scientist Inc. in association with BioMed
Central
-
-
- Patricia A. Doyle, PhD
- Please visit my "Emerging Diseases" message
board at: http://www.clickitnews.com/ubbthreads/postlist.php?Cat=&Board=emergingdiseases
- Zhan le Devlesa tai sastimasa
- Go with God and in Good Health
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