Cytosine Arabinoside Therapy for Herpes Simplex Encephalitis—Clinical Experience with Six Patients

Abstract

Two neonates and four adults with herpes simplex virus (HSV) encephalitis were treated with cytosine arabinoside (Ara-C). A low dose of 40 to 160 mg per m 2 per day was given for 4 to 6 days by continuous intravenous infusion and, except in two cases, by intrathecal administration. In one patient, idoxuridine (IUdR) at the dose of 1 g every 4 h was also administered after 4 days of Ara-C therapy. Both neonates and two of four adults survived. Their clinical improvement was closely related in time to the onset of therapy with Ara-C (cases 1, 2, 3) and with IUdR (case 4). In one adult who died on the 27th day of illness of a massive pulmonary embolus, postmortem examination of the brain did not disclose viral inclusions, and viral culture was negative. In the other patient who died, however, brain culture postmortem was still positive for HSV despite 4 days of Ara-C therapy. Ara-C, in addition to IUdR, may be effective in HSV encephalitis treatment, but double-blind, controlled studies appear to be necessary with these agents.

Synergistic antiviral activity of acyclovir and interferon on human cytomegalovirus

“…Each of these compounds was initially shown to be an effective inhibitor of herpes simplex virus (HSV) and has been used to treat HSV infections (4,5,10,13,23). However, due to problems of low therapeutic indices and isolation of HSV resistant to these antiviral agents, studies have been undertaken to examine the potential of polychemotherapy in the treatment of HSV infections.…”

The contribution of virology to contemporary medicine.

“…This has been accompanied by a decline in the disease to a very low level ( recovery of poliovirus has been maintained by the Public Health Laboratory Service (Miller, Reid, and Diamond, 1970). The polioviruses recovered in the laboratory of recent years have largely possessed the cultural properties of attenuated virus strains (Cossart and Whitehouse, 1973). They were probably derived from the vaccine viruses which infect the throat and are excreted in the faeces.…”

“…Cytarabine is believed to exert its action by competitive inhibition of DNA synthesis for it is a pyrimidine nucleoside. It has been used in the treatment of herpes encephalitis (Chow et al, 1973), smallpox (Hossain et al, 1972;Dennis et al, 1974) (1973)). …”

Acyclovir therapy of neonatal herpes simplex virus type 2 infections in rabbits

“…In contrast, animals treated with acyclovir failed to develop significant skin lesions, and death did not occur while treatment continued. Termination of treatment after 6 days resulted in late-onset fatal disease and virus isolation from the brain in many rabbits regardless of the treatment schedule. No such late fatality was observed and no virus could be detected from the brain when treatment was initiated on the day of virus inoculation and continued for 12 consecutive days.…”

“…No such late fatality was observed and no virus could be detected from the brain when treatment was initiated on the day of virus inoculation and continued for 12 consecutive days. With respect to all of the variables studied, treatment for 12 days beginning on the day of virus inoculation was most effective.In the past, iododeoxyuridine (4,15,16,19,23,26,31), cytosine arabinoside (6,27), and adenine arabinoside (5, 32) have been used in the treatment of herpes simplex virus (HSV) infections in newborns with varied results. Toxicity, rapid metabolic breakdown, or insolubility of these compounds further limited their therapeutic use.…”