Posted on 10/19/2001 10:11:43 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.
FROM EMEDICINE - AN ONLINE MEDICAL JOURNAL - October 17 2001, Volume 2, Number 10: SMALLPOX
Drug Category: Antivirals - In vitro studies demonstrated cidofovir to inhibit poxvirus replication and cell lysis.
| Drug Name |
Cidofovir (Vistide)- A nucleoside analog DNA polymerase inhibitor; if administered within 48 h of exposure, may attenuate or avoid infection; adefovir, cidofovir, and ribavirin are under investigation for smallpox. Ribavirin as an aerosol treatment for pediatric respiratory syncytial virus is under investigation. |
|---|---|
| Adult Dose | 5 mg/kg IV over 1 h |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; coadministration with other nephrotoxic agents; serum creatinine >1.5 mg/dL; CrCl <55 mL/min; urine protein >100 mg/dL |
| Interactions | Coadministration of aminoglycosides, amphotericin B, IV pentamidine, and foscarnet may increase nephrotoxicity |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Complications include renal toxicity, neutropenia, fever, anemia, headache, hair loss, uveitis and/or iritis, and abdominal pain; monitor neutrophil counts; IV prehydration with NS and coadministration of probenecid can minimize nephrotoxicity; monitor serum creatinine and urine protein 48 h prior to treatment (adjust dose accordingly) |
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)...
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. (MY NOTE: CMV is of the herpes-family of viruses - of which smallpox is a member) 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...
The drug cidofovir (Vistide) is approved, classified as an experimental treatment, and is being made available to thousands, possibly millions of AIDS patients. But it will not be made available even as an option to U.S. Smallpox patients who might be saved by it. Bottom line: Cidofovir is available, and appears to be an effective (if not absolute) treatment for smallpox. BUT ACCORDING TO THE NYC DEPT OF HEALTH website it will NOT BE OFFERED due to the fact it is in vitro - experimental. If threatened by smallpox, we should be offered the option to access it for treatment. We need to start asking questions NOW if we want to be able to access this possibly life-saving treatment...
Perhaps it would do to give them a Toll-Free Call at (800) 445-3235 and ask them if it will be available for smallpox victims...
The U.S. Department of Health and Human Services
200 Independence Avenue, S.W.
Washington, D.C. 20201
(202) 619-0257
Toll Free: 1-877-696-6775
Or you may choose to contact any of these public servants through e-mail...
Unfortunately, you would need a booster to maintain your resistance (about every 10 years).
I thought the same thing.I know that I was vaccinated for smallpox in the Navy too as well as a number of other things. Over a 26 year career I was needled and air gunned so many times it was hard to keep up with all the details. I do know the I had shots for bubonic plague once and I wonder if that one is permanent or needs a booster too.
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