Progressive vaccinia.

The resumption of smallpox vaccination for health care workers and other first responders has raised concern about the occurrence of complications in people with immunodeficiency disorders, including those infected with human immunodeficiency virus. During the era of universal vaccination, roughly 1 person per million vaccinees in the general population developed progressive vaccinia, which is characterized by the relentless outward spread of infection from the vaccination site and eventual dissemination to other areas on the body. Review of 56 cases reported in the English-language medical literature from 1893 through 1997 indicates that the condition occurred only in persons with severe cell-mediated immunodeficiency. Progressive vaccinia was found to be lethal in infants who completely lacked cellular immune function, but infection resolved in many adults with acquired immunodeficiency. Almost all cases were treated with vaccinia immune globulin, but its efficacy has never been tested in a placebo-controlled trial. Further research is needed to develop effective forms of therapy.

Antiviral agents.

Only a few agents with antiviral activity are available for routine clinical use. Amantadine hydrochloride is effective in the prophylaxis of influenza A. In addition, accumulated evidence shows that amantadine has some therapeutic effect when used early in the course of an influenza A infection. Idoxuridine and adenine arabinoside have found application as topical agents in the treatment of herpes simplex keratitis. Adenine arabinoside has also been approved for the treatment of disseminated infections due to herpes zoster and herpes simplex. Acyclovir sodium has been approved as a topical agent in the treatment of limited mucocutaneous herpes simplex viral infections in immunosuppressed patients and of initial episodes of genital herpes simplex infections in patients with normal immunity. Ribavirin, an experimental agent with a wide spectrum of activity in vitro, has not fulfilled expectations in clinical trials. Because of the eradication of smallpox, methisazone has become obsolete as a prophylactic agent in smallpox.

Methisazone therapy in pediatric vaccinia complications.

Methisazone 40 mg/kg/day was administered orally to six pediatric and one adult patient who contracted vesicular complications affecting the skin or mucocutaneous junctions 3 to 9 days after antismallpox vaccination, and to one elderly man with myeloid leukemia who developed vaccinia necrosum. Therapy was commenced 2 to 10 days after onset of complications and was administered for 3 days. All patients with skin or mucocutaneous complications showed dramatic clinical responses within one day after commencement of antiviral chemotherapy, and complete recovery occurred within one week. Clinical improvement was noted 4 days after therapy was begun in the case of vaccinia necrosum, and recovery occurred after 3 weeks.

Evaluation of ectodermal lesions in intravenous vaccinia infected mice as a method to investigate the antiviral activity of isatin beta-thiosemicarbazone derivative (TSK VI compound).

In this paper ectodermal lesions on the tails of mice inoculated intravenously with vaccinia virus were used to study the influence of N,N'-bis[methylisatin-beta-thiosemicarbazone]-2-methylpiperazine (TSKI VI) on the number and dynamics of lesion formations. The activity of this compound was compared to that of the antiviral drug, methisazone. The reduction in lesions after treatment with TSKI VI was similar to the reduction induced by methisazone, which, on the basis of earlier theroretical and experimental data as well as on the lower toxicity of TSKI VI for the tissues and a more favorable therapeutic index, makes this compound worth considering in the treatment of postvaccinal complications. This method proved very useful in examination of the substances having potential prophylactic properties in preventing generalized infections.

Immune response in vaccinia virus infected mice treated with N,N'-bis/methylisatin-beta-thiosemicarbazone/-2-methylpiperazine.

The effect of the compound N,N'-bis/methylisatin-beta-thiosemicarbazone/-2-methylpiperazine (bis-MIBTP) on immune response in BALB/c and Swiss mice have been studied in the course of vaccinia virus infection. Humoral response tested by neutralization and hemagglutination inhibiting antibodies was similar in compound-treated mice to this of untreated mice. Cell-mediated immune response, examined by spleen lymphocytes migration inhibition test, has been delayed or temporally depressed in bis-MIBTP treated mice as compared with the control group. High protective activity of the compound in vaccinia infected mice in spite of impairment of cellular immunity may indicate that antibodies have played an important role in recovery process from vaccinia infection.

Effect of N, N'-bis(methylisatin-beta-thiosemicarbazone)-2-methylpiperazine against virus-induced encephalitis in mice).

N,N'-bis(methylisatin-beta-thiosemicarbazone)-2-methylpiperazine (TSKI-VI) proved to be significantly effective against lethal vaccinia, pseudorabies and Mengo virus-induced encephalitis in different strains of mice when administered subcutaneously (s.c.) in doses of 20 mg/kg body weight, twice daily, for a period of five days. The strongest effects occurred in vaccinia virus-infected mice, and the degree of protection was both dose- and virus-dependent. Titres of vaccinia virus in brains of infected mice were slightly lower in TSKI-VI or methisazone-treated mice as compared to virus controls.

Effect of N,N'-bis(methylisatin-beta-thiosemicarbazone)-2-methylpiperazine on vaccinia virus replication in vitro and in vivo. Brief report.

The inhibitory effect of N,N'-bis(methylisatin-beta-thiosemicarbazone)-2-methylpiperazine (compound TSKI-VI) and methisazone (Marboran) on the growth of vaccinia virus (IHD strain) was studied in vitro and in vivo. The therapeutic indices of both compounds determined in vivo were similar, but TSKI-VI was found more efficient in vitro.