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

Abstract

New Zealand white rabbits less than 30 h old were inoculated subcutaneously with 103 50% tissue culture infectious doses of type 2 herpes simplex virus. The animals were randomly assigned to a treatment schedule of daily intraperitoneal injections of acyclovir, beginning on the day of virus inoculation for 6 or 12 days, on post-inoculation day 1 for 6 days, or on post-inoculation day 2 for 6 days. The acyclovir was given in doses of 50 mg/kg of body weight per day. Similarly infected animals receiving daily intraperitoneal injection of Eagle minimum essential medium served as controls. All of the control animals died on day 4 or 5 after inoculation. At death they exhibited severe skin lesions, viremia, and dissemination of virus in various visceral organs and spinal as well as trigeminal ganglia. 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. 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. Acyclovir (ACV) [9-(2-hydroxyethoxymethyl)-guanine], formerly known as "acycloguanosine," is an attractive candidate for treatment of neonatal HSV infections, since it has a high level of activity against HSV infections both in vitro (10) and in vivo (17, 28) with minimal toxicity in vivo (9,28,29). This paper reports the results on a study on the efficacy of ACV against HSV type 2 (HSV-2) skin infections in newborn rabbits, an experimental model described previously (20). MATERIALS AND METHODSNewborn rabbits. New Zealand white rabbits 24 to 30 h old were used as in our previous study (20 by dissolving 225 mg of ACV in 10 ml of 0.1 N NaOH, sterilizing by filtration through a membrane filter (Millipore Corp., Bedford, Mass.), and adjusting to pH 8.0 with 0.1 N HCI. The sterile stock ACV solution was stored at 4°C and further diluted in minimal essential medium to obtain the concentration of 5 mg/ ml as needed.Collection of blood and tissue specimens for virus assay and histopathology. Immediately after sacrifice, 2 ml of cardiac blood was obtained, heparinized, and processed for virus isolation. Duplicate specimens of heart, lungs, thymus, liver, spleen, kidneys, brain, and both adrenal glands and eyes were removed. One specimen or organ was fixed in Bouin solution for histological study, and th...

Efeitos do Foscarnet sobre a infecção pelos herpesvírus bovino tipos 1 e 5 em coelhos

“…Embora este procedimento não reflita o que se realiza na rotina -início da terapia após o início dos sinais clínicos -é uma prática comum em estudos com antivirais in vivo (Sicher et al 1981, Thiry et al 1983, Kern et al 1986, Öberg et al 1989. É possível que se o tratamento fosse iniciado antes (ex.…”

“…A maioria deles relata estudos com o Aciclovir (ACV) em camundongos ou em coelhos inoculados com o HSV-1, que servem como modelo para uso de antivirais em humanos (Sicher et al 1981, Kern et al1986). Em estudos clínicos, a atividade do PFA já foi demonstrada frente ao citomegalovírus murino (MCMV), reduzindo a mortalidade e os títulos de vírus nos pulmões de ratos infectados (Debs et al 1986).…”