Skip to comments.EFFECTIVE TREATMENT FOR SMALLPOX - Cidofovir - BUT NOT FOR YOU
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
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.)
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...
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...
It is very difficult to use-it is IV (intravenous) only, and causes major side effects, including kidney failure severe enough to require discontinuation, in over 50% of those treated.
The IV infusion itself is difficult and prolonged.
I am interested in the reference to ribavirin, which is used to treat Hepatitis C and is now available in large quaantities both here and overseas.
Since we have nothing better, and those who have been studying it have come up with suggested doses, it begs the question - will we be given the option to try cidofovir, considering that it's risks are - by all accounts - significantly lower than that of smallpox?
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