Field Trials of Methisazone as a Prophylactic Agent Against Smallpox1

Heiner, Gordon G.; Fatima, Nusrat; Russell, Philip K.; Haase, Ashley T.; Ahmad, Nur Izzah Izzati; Mohammed, Niaz; Thomas, David B.; Mack, Thomas M.; Khan, Malik M. Khurram S.; Knatterud, Genell L.; Anthony, Ronald L.; McCrumb, Fred R.

doi:10.1093/oxfordjournals.aje.a121340

Cited by 48 publications

(21 citation statements)

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“…Historically, marboran® was used to treat smallpox virus infections (Heiner et al, 1971). From the responses of patients to treatment it was concluded that the drug was largely ineffective.…”

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confidence: 99%

Antiviral Activity and Mode of Action Studies of Ribavirin and Mycophenolic Acid against Orthopoxviruses in Vitro

Smee

Bray

Huggins

2001

Antivir Chem Chemother

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triphosphate forms of the drug compared with Vero 76 cells. For both MPA and ribavirin, virus inhibition was closely correlated to the extent of suppression of intracellular guanosine triphosphate (GTP) pools. Treatment with extracellular guanosine (which restored intracellular GTP levels) did not lead to complete reversal of the anticowpox virus activity of ribavirin. This suggests that other modes of virus inhibition also appear to contribute to the anti-orthopoxvirus activity of ribavirin. Biological differences in mode of action and immunosuppressive potential between ribavirin and MPA may account for why the former compound is active against orthopoxvirus infections in animals and the latter inhibitor is not.

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mentioning

confidence: 99%

Antiviral Activity and Mode of Action Studies of Ribavirin and Mycophenolic Acid against Orthopoxviruses in Vitro

Smee

Bray

Huggins

2001

Antivir Chem Chemother

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“…Treatment and control groups were incompletely randomized, with a possible bias in favor of methisazone. A subsequent fully randomizedbut considerably smaller-trial reported favorable but lessimpressive results (the incidence of smallpox in the control group was almost double that in the methisazone group) [50]. This finding did not reach statistical significance.…”

Section: Prophylaxismentioning

confidence: 90%

Rethinking Smallpox

Weiss¹,

Weiss²,

Mathisen³

et al. 2004

CLIN INFECT DIS

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The potential consequences of a competently executed smallpox attack have not been adequately considered by policy makers. The possibility of release of an aerosolized and/or bioengineered virus must be anticipated and planned for. The transmission and infectivity of variola virus are examined. Arguments for and against pre-event vaccination are offered. The likely morbidity and mortality that would ensue from implementation of a mass pre-event vaccination program, within reasonable boundaries, are known. The extent of contagion that could result from an aerosolized release of virus is unknown and may have been underestimated. Pre-event vaccination of first responders is urged, and voluntary vaccination programs should be offered to the public. Two defenses against a vaccine-resistant, engineered variola virus are proposed for consideration. Methisazone, an overlooked drug, is reported to be effective for prophylaxis only. The extent of reduction in the incidence of smallpox with use of this agent is uncertain. It is useless for treatment of clinical smallpox. N-100 respirators (face masks) worn by uninfected members of the public may prevent transmission of the virus.

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“…vaccinia gangrenosa and eczema vaccinatum (Fenner and White, 1970). In a double-blind field trial, however, others were unable to confirm the prophylactic activity of methisazone against smallpox (Heiner et al, 1971). Following successful implementation of the smallpox vaccine, the use of methisazone was not further pursued.…”

Section: Thiosemicarbazonesmentioning

confidence: 99%

Selective inhibitors of the replication of poxviruses

Neyts

Clercq

2006

New Concepts of Antiviral Therapy

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Abstract:In case of an inadvertent epidemic with the smallpox virus that could not immediately (or not only) be controlled by vaccination, it will be of utmost importance to have effective antiviral drugs at hand for treatment and/or shortterm prophylaxis. Most advanced as a therapeutic or early prophylactic modality is cidofovir, a compound that has been licensed (as Vistide®) for the intravenous treatment of CMV retinitis in AIDS patients. Cidofovir is active in vitro against all (ortho)poxviruses studied so far; is effective in various relevant animal models, including cynomolgus monkeys infected with the monkeypox virus, and has shown efficacy in the clinical setting for the treatment of infections with molluscum contagiosum and orf. Cidofovir should also allow to treat severe complications of vaccination, as may occur in immunodeficient patients. Recently a selective non-nucleoside inhibitor of orthopoxvirus replication (ST-246) was reported that targets a major envelope protein that is involved in viral maturation and the production of infectious extracellular virus. ST-246 exhibits potent activity in mouse models of poxvirus infection. Also, the Abl-family tyrosine kinases and the ErbB-1 kinase were shown to play a crucial role in the replication cycle of poxviruses. Hence inhibitors of these kinases, turned out to be selective inhibitors of poxvirus replication, both in cell culture and in experimentally infected animals.

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Field Trials of Methisazone as a Prophylactic Agent Against Smallpox1

Cited by 48 publications

References 0 publications

Antiviral Activity and Mode of Action Studies of Ribavirin and Mycophenolic Acid against Orthopoxviruses in Vitro

Antiviral Activity and Mode of Action Studies of Ribavirin and Mycophenolic Acid against Orthopoxviruses in Vitro

Rethinking Smallpox

Selective inhibitors of the replication of poxviruses

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