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EFFECTIVE TREATMENT FOR SMALLPOX - Cidofovir - BUT NOT FOR YOU
Office of Evaluation, Government Performance and Results Act - http://www1.od.nih.gov/gpra/ ^ | 2000 - 2001 (various release dates for studies) | Martinez, Bray, Huggins, ETAL

Posted on 10/19/2001 12:43:31 AM PDT by dandelion

FROM THE NATIONAL INSTITUTE OF HEALTH WEBSITE
New Drug to Aid in Protection Against Bioterrorism.

Although smallpox was eradicated in the 1970's, smallpox has re-emerged as a public health concern because of its potential use as a biowarfare agent. At present, no drugs exist to treat orthopoxviruses, the family of respiratory-transmitted viruses of which smallpox is a member. Recently, NIH-supported investigators tested the efficacy of a drug called cidofovir against these viruses. Cidofovir is currently licensed to treat an unrelated disease. The investigators, expanding upon prior findings by another research team, found that cidofovir inhibits a broad spectrum of orthopoxviruses in vitro, completely protects monkeypox-infected monkeys from signs of disease, and is highly effective in protecting and treating cowpox virus in mice. These findings suggest cidofovir may be effective treatment for smallpox infection.

Martinez MJ, Bray MP,Huggins JW: A mouse model of aerosol-transmitted orthopoxviral disease. Archives of Pathological Laboratory Medicine, 124(3):362-77. 2000.
Smee DF, Bailey KW, Wong M-H, Sidwell RW: Intranasal treatment of cowpox virus respiratory infections in mice with cidofovir. Antiviral Chemical Chemotherapy, 11(4):303-9. 2000.

Text available HERE (cached text from Google)

FROM THE CDC: PREPAREDNESS FOR SMALLPOX - ANTIVIRAL DRUGS
Antiviral Drugs
Two hundred seventy-four antiviral drug compounds were screened for activity and therapeutic indices against variola, monkeypox, cowpox, camelpox, and vaccinia viruses by two cell culture assays. Many of these compounds were provided for testing under collaborative arrangements facilitated by an orthopox antiviral research initiative of the National Institute of Allergy and Infectious Diseases. Previous studies identified a nucleoside phosphonate DNA polymerase inhibitor, cidofovir (Vistide), as being active against poxviruses, including variola. In the current trial, cidofovir and its prodrug (cyclic HPMPC) were evaluated against 31 strains of variola, which were selected to cover a wide geographic area and time span. No substantial differences in inhibition among strains were observed, which suggests that cidofovir-resistant strains are unlikely. The in vitro inhibition was further characterized in multiple cell lines to meet FDA requirements. However, another class of antiviral drugs, the S-adenosylhomocysteine hydrolase inhibitors, showed considerable variation in the 50% inhibitory dose between variola isolates; this effect should be investigated further.

Two approaches to the development of an oral prodrug of cidofovir yielded compounds with improved antiviral activity. In addition, the current series of experiments identified 27 other compounds, including completely new classes of drugs, that appear to be active against variola and other orthopoxviruses. In fact, 10 compounds had therapeutic indices greater than 200, while cidofovir had indices greater than 10; 3 compounds had therapeutic indices greater than 1,500. When work resumes in early 2001 with live variola virus, we will continue to evaluate these and additional compounds for activity, including analogs designed for oral administration. The most promising compounds emerging from this in vitro testing will be evaluated in animal models, e.g., cowpox and vaccinia in mice and eventually monkeypox virus challenge in nonhuman primates. All promising compounds will be tested against a battery of surrogate orthopox viruses to guide evaluation of new antiviral compounds after variola virus is no longer available.

THIS FROM NYC DEPT OF HEALTH: Medical Treatment and Response to Suspected Smallpox: Information for Health Care Providers During Biologic Emergencies
Treatment: Supportive care is the mainstay of therapy In-vitro antiviral activity against poxviruses has been shown with adefovir, cidofovir, dipivoxil, and ribavirin. (Animal studies suggest that cidofovir may be most effective.)
***BUT***
VII.Treatment Supportive care is the mainstay of therapy. Currently, there are no anti-viral drugs of proven efficacy. Although, adefovir, dipivoxil, cidofovir and ribavirin have significant in vitro antiviral activity against poxviruses, their efficacy as therapeutic agents for smallpox is currently uncertain. Cidofovir is FDA-licensed and shows the most promise in animal models.

ADDITIONAL INFORMATION REGARDING CIDOFOVIR:
Cidofovir (trade name Vistide, formerly known as HPMPC) is a treatment for CMV retinitis. CMV is a common infection caused by a herpesvirus called cytomegalovirus. About half of the US population are infected with CMV, but the immune system normally prevents the virus from causing illness. In people with immune system problems such as AIDS, CMV can become active and cause illness. The greatest risk for CMV-related illnesses is for people with T-cell counts of less than 50...
Gilead Sciences, the company that makes cidofovir, has set up a patient assistance program for people having difficulty accessing the drug. Call (800) 445-3235 for more information...


TOPICS: Front Page News; News/Current Events
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To: dandelion
We need to start asking questions NOW if we want to be able to access this possibly life-saving treatment...

One thing I do not get about things like Small Pox or AIDS is that liberals who have been acting like victims because of AIDS have supported the same government that restricts the much needed widespread individual entrepreneurialism for the sake of finding cures. I am sorry, but gay people are dead wrong to be anti-conservatives simply because being conservative is an advocacy of opposit sex marriage unions.

21 posted on 10/19/2001 2:53:10 AM PDT by lavaroise
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To: Jim Noble
This in response to the difficulty in administration, and in the need to discontinue due to renal side effects:

According to this document, the dosage would be a one-time IV within 48 hours of exposure: 5 mg/kg IV over 1 h. This vastly differentiates smallpox treatment with cidofovir from the treatment of CMV with the same, since treatment of CMV is ongoing for the life of the patient. According to this study, they believe this one-time, one-hour IV dose will significantly attenuate or even avoid infection with smallpox if administered within 48 hrs of infection - certainly worth the difficulty of administration, and certainly worth the risk of renal damage if administered with proper accompanying medications (probenecid)...

22 posted on 10/19/2001 3:02:57 AM PDT by dandelion
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To: dandelion
it begs the question - will we be given the option to try cidofovir ?

Have you asked your M.D. this important question?

23 posted on 10/19/2001 3:03:28 AM PDT by dbbeebs
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To: dbbeebs
I just found this information this evening, and yes, I plan on asking. However, that being said, I doubt sincerely that in the event of a smallpox outbreak that our local family M.D.'s will be allowed to treat those exposed to the disease - if I am correct, all those who are believed to be exposed will be strictly quarantined. At that point, we will have to deal with what they give us, regardless of what we want.
24 posted on 10/19/2001 3:06:09 AM PDT by dandelion
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To: beacon
Hi beacon, wanna see if this story might have legs?
25 posted on 10/19/2001 3:12:48 AM PDT by dandelion
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To: Jim Noble
Ribavirin may be the ONLY option for pediatric care - I'm not sure if Cidofovir would be indicated at any level for children. It bears looking into the matter more deeply - is this drug widely available?
26 posted on 10/19/2001 3:17:33 AM PDT by dandelion
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To: dandelion
HEADS UP FOLKS WE'VE MADE SOMEONE NERVOUS - the National Institute of Health link appears to be ALREADY GONE! Quick folks - go to the link provided for google's cache, then click on the link at the top of the page it will lead you to a PDF (adobe) file. DOWNLOAD THAT FILE and print it out before it disappears forever! I have a feeling we may have just opened a can of worms - I wonder how they heard about little old us...
27 posted on 10/19/2001 3:55:26 AM PDT by dandelion
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To: dandelion
ribavirin is easily administered orally, and is produced in large quantities.
28 posted on 10/19/2001 4:18:53 AM PDT by Jim Noble
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Comment #29 Removed by Moderator

To: crystal55t
They are in places like China, with the result that many more infections there are antibiotic resistant as bacteria mutate and backfill their ecological niches with new resistant strains. This affects not just the patients choosing to self medicate, but everybody else subject to those germs. (Fortunately IIRC once the antibiotic overuse is stopped, the bacteria eventually revert back to their "wild" state.)
30 posted on 10/19/2001 4:31:14 AM PDT by HiTech RedNeck
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To: dandelion
A Good Morning bump.
31 posted on 10/19/2001 5:04:20 AM PDT by Dixielander
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To: dandelion
downloaded from google cache -- thanks!
32 posted on 10/19/2001 5:10:44 AM PDT by SauronOfMordor
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To: dandelion
I was thinking: I read somewhere that milking cows with cowpox gives you a very mild form of the disease and gives you immunity from smallpox.

If it's true, shouldn't we organize a "PET THE COWPOXED COW" day for children? I'm asking FR doctors here. Would it be possible to do it in case of a national emergency? and no, I'm NOT kidding.

33 posted on 10/19/2001 5:53:41 AM PDT by Elenya
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To: dandelion
>if administered within 48 hrs of infection -

That's a problem. Smallpox, from what I read, doesn't show obvious symptoms for a few days post infection. So how do you know the person doesn't have the flu, or some other disease? How do you know for sure who has been exposed to Smallpox?

34 posted on 10/19/2001 6:36:21 AM PDT by Darnright
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To: SauronOfMordor
I just tried and it was gone...
35 posted on 10/19/2001 6:58:16 AM PDT by CathyRyan
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To: dandelion
Bump
36 posted on 10/19/2001 7:44:51 AM PDT by CathyRyan
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To: Darnright
If a known contact of yours has the contracted smallpox, you will be quarantined by the health authorities. If you know that contact has been in the last 48 hours, you need to ask for cidofovir or one of the other experimental treatments - but if they are acting like it doesn't exist, that may be hard to do...
37 posted on 10/19/2001 9:17:08 AM PDT by dandelion
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To: CathyRyan
THREAD II here...
38 posted on 10/19/2001 10:43:06 AM PDT by dandelion
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To: CathyRyan
I just tried and it was gone...

Here ya go (just posting the relevant section):


 New Drug to Aid in Protection Against Bioterrorism.  Although smallpox was eradicated in the 
1970's, smallpox has re-emerged as a public health concern because of its potential use as a biowarfare 
agent. At present, no drugs exist to treat orthopoxviruses, the family of respiratory-transmitted viruses of 
which smallpox is a member.  Recently, NIH-supported investigators tested the efficacy of a drug called 
cidofovir against these viruses.  Cidofovir is currently licensed to treat an unrelated disease.  The 
investigators, expanding upon prior findings by another research team, found that cidofovir inhibits a 
broad spectrum of orthopoxviruses in vitro, completely protects monkeypox-infected monkeys from 
signs of disease, and is highly effective in protecting and treating cowpox virus in mice.  These findings 
suggest cidofovir may be effective treatment for smallpox infection.  
 Martinez MJ, Bray MP,Huggins JW:  A mouse model of aerosol-transmitted orthopoxviral disease.  Archives of 
Pathological Laboratory Medicine, 124(3):362-77. 2000.  
 Smee DF, Bailey KW, Wong M-H, Sidwell RW:  Intranasal treatment of cowpox virus respiratory infections in mice 
with cidofovir.  Antiviral Chemical Chemotherapy, 11(4):303-9. 2000. 

39 posted on 10/19/2001 1:29:19 PM PDT by SauronOfMordor
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To: SauronOfMordor
Thank you, that was nice of you to do that. :)
40 posted on 10/19/2001 2:17:01 PM PDT by CathyRyan
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