Mean Day Of Death Research Articles

P-PN005. The clinical characteristics and incidence of hypoalbuminemia in patients with guillain barré syndrome in yogyakarta, indonesia

Introduction . GBS is an acute polyradiculoneuropathy typically presenting with sensory symptoms and weakness. Approximately 70% of patients report a recent preceding inflammation process. Investigators of large, worldwide, collaborative studies of the spectrum of GBS are accruing data for clinical databases to inform the development of outcome predictors and disease biomarkers. The low of serum albumin level, as the most abundant protein in plasma, may be related to acute systemic inflammatory reaction. In this study, we investigate the clinical characteristics and incidence of hypoalbuminemia in patients with GBS. Methods . We retrospectively analyzed the clinical data of adult GBS, between 2014 to 2019, from medical record of the patients hospitalized at Dr.Sardjito Hospital, as central district hospital in Yogyakarta. Serum albumin concentration was determined before treatment. Results . There were 73 patients were enrolled in this study. We found that male was slightly more affected than female (53,4% vs 46,6%). The elderly patients (60 years) were less than adult non-elderly patients (19% vs 81%). The adult age varied from 18 year to 78 years. During hospitalization, the mean length of stay (LOS) were 24 days (range from 4 days to 154 days). The in-hospital mortality rate was 9.6% (7 of 73 patients), while 66 (90,4%) patients with GBS were alive at discharge. The mean day of death were 40 days, longer than the mean of LOS, indicating the complication during treatment may happened. Before treatment, the mean serum albumin level was 4.03 g/dL with hypoalbuminemia (albumin<3.5 g/dL) in 10 (14%) of 73 patients. Conclusion . The incidence of GBS decreased with age. The mortality may happen in long- term of hospital treatment. There is a low incidence of hypoalbuminemia in acute GBS. Further studies are required to confirm the correlation between hypoalbuminemia and the severity of clinical course in patients with GBS.

PROTECTIVE ACTIVITY OF NOVEL BENZIMIDAZOLE DERIVATIVES AT EXPERIMENTAL INFLUENZA INFECTION

Influenza is an acute respiratory viral infection, which represents an important health problem. Every year, influenza causes epidemics and pandemics, leading to increase in morbidity and mortality in all regions of the globe. Due to the segmental organization of the genome and low accuracy of its replication, the influenza virus is capable of escaping the host’s immune response (antigenic drift), as well as the selection of drug-resistant variants. This calls for constant monitoring of the sensitivity of viral isolates to antiviral drugs and the development of new etiotropic antiviral agents that have alternative targets and mechanisms of activity. The purpose of this study was to characterize the new aminobenzimidazole derivatives as protective agents in lethal influenza infection in white mice. The efficacy of the compounds was assessed by their ability to reduce specific mortality of animals in the course of lethal influenza pneumonia caused by the influenza A/Puerto Rico/8/34 (H1N1) irus, increase the life duration of animals, and normalize the morphological structure of lung tissue comparing to the placebo group. For all the compounds studied, a decrease in the specific mortality of animals (from 20 to 60%) has been shown. The reference drug (oseltamivir phosphate) reduced the mortality of mice by 80%. The benzimidazole derivative 2519 demonstrated the highest indices of protective activity, its use reduced the mortality of animals by 60% and increased their mean day of death by 1.6 days in comparison with the control group. Morphological analysis showed that the activity of derivative 2519 was manifested in the normalization of the morphological structure of lung tissue in the course of influenza pneumonia. On day 5 after infection, the cells of the bronchial epithelium looked intact, in contrast to destroyed cells with numerous viral inclusions in control animals. The foci of inflammation themselves occupied a smaller area compared to the control. At the same time, there was no correlation between the previously obtained data on the virus-inhibiting effect of these compounds in vitro and the data obtained in animals. This suggests that despite the presence of direct antiviral activity detected previously in in vitro experiments, the protective properties of the studied aminobenzimidazoles on animals are caused, in addition to the etiotropic effect, by other pathogenetic factors. In conclusion, amino derivatives of benzimidazole should be considered as compounds that are promising for further development and introduction as an anti-influenza agents.

Abstract No. 486 - Percutaneous cholecystostomy: institutional experience and outcomes

Abstract No. 486 - Percutaneous cholecystostomy: institutional experience and outcomes

Soft-X-Ray-Enhanced Electrostatic Precipitation for Protection against Inhalable Allergens, Ultrafine Particles, and Microbial Infections

Protection of the human lung from infectious agents, allergens, and ultrafine particles is difficult with current technologies. High-efficiency particulate air (HEPA) filters remove airborne particles of >0.3 μm with 99.97% efficiency, but they are expensive to maintain. Electrostatic precipitation has been used as an inexpensive approach to remove large particles from airflows, but it has a collection efficiency minimum in the submicrometer size range, allowing for a penetration window for some allergens and ultrafine particles. Incorporating soft X-ray irradiation as an in situ component of the electrostatic precipitation process greatly improves capture efficiency of ultrafine particles. Here we demonstrate the removal and inactivation capabilities of soft-X-ray-enhanced electrostatic precipitation technology targeting infectious agents (Bacillus anthracis, Mycobacterium bovis BCG, and poxviruses), allergens, and ultrafine particles. Incorporation of in situ soft X-ray irradiation at low-intensity corona conditions resulted in (i) 2-fold to 9-fold increase in capture efficiency of 200- to 600-nm particles and (ii) a considerable delay in the mean day of death as well as lower overall mortality rates in ectromelia virus (ECTV) cohorts. At the high-intensity corona conditions, nearly complete protection from viral and bacterial respiratory infection was afforded to the murine models for all biological agents tested. When optimized for combined efficient particle removal with limited ozone production, this technology could be incorporated into stand-alone indoor air cleaners or scaled for installation in aircraft cabin, office, and residential heating, ventilating, and air-conditioning (HVAC) systems.

Evaluation of imiquimod for topical treatment of vaccinia virus cutaneous infections in immunosuppressed hairless mice

Imiquimod is an immune response modifier prescribed as a topical medication for a number of viral and neoplastic conditions. We evaluated the antiviral activity of imiquimod against vaccinia virus (WR strain) cutaneous infections in immunosuppressed (with cyclophosphamide) hairless mice when administered after virus exposure. Primary lesions progressed in severity, satellite lesions developed, and infection eventually killed the mice. Once daily topical treatment with 1% imiquimod cream for 3, 4, or 5 days were compared to twice daily topical treatment with 1% cidofovir cream for 7 days. Survival time of mice in all treated groups was significantly prolonged compared to placebo controls. The mean day of death for the placebo group, 3-day imiquimod, 4-day imiquimod, 5-day imiquimod, and cidofovir groups were 15.5, 20.0, 20.5, 19.5, and 20.5 days post-infection, respectively. All treatment groups showed significant reductions in primary lesion size and in the number of satellite lesions. The cidofovir and 4-day imiquimod treatments delayed the appearance of lung virus titers by 3 and 6 days, respectively, although cutaneous lesion and snout virus titers were not as affected by treatment. Benefits in survival and lesion reduction were observed when imiquimod treatment was delayed from 24, 48, and 72 h post-infection. However, increasing the treatment dose of imiquimod from 1% to 5% led to a significant decrease in antiviral efficacy. These results demonstrate the protective effects of topically administered imiquimod against a disseminated vaccinia virus infection in this mouse model.

Antiviral Activity of a Carrageenan fromGigartina skottsbergiiagainst Intraperitoneal MurineHerpes simplexVirus Infection

The partially cyclized mu/nu-carrageenan 1C3, isolated from the red seaweed Gigartina skottsbergii, was previously shown to be a potent inhibitor of the in vitro replication of Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Here the protective effect of 1C3 in a murine model of intraperitoneal ( i. p.) HSV-1 infection was evaluated. OF1 mice were i. p. infected with 5 x 10 (5) PFU of HSV-1 KOS strain, and the effects of different treatments with 1C3 were studied. When 30 mg/kg of body weight of 1C3 was administered by the i. p. route immediately after HSV-1 infection, 87.5 % survival of the animals was achieved (p < 0.005), associated with a delay in the mean day of death in 1C3-treated non-surviving mice. Animal survival was not improved when multiple doses of 1C3 were also given in the period 1 - 48 h post-infection, and no protection was afforded when treatment was started after 24 h of infection. When virus and compound were injected by different routes, i. p. and intravenous ( i. v.), respectively, a still significant protection was achieved (40 % survival, p < 0.05). No toxicity of 1C3 for the animals was recorded. The pharmacokinetic properties were analyzed after injection of 1C3 into the tail vein by monitoring of [ (3)H]-1C3 in plasma and organs and by a bioassay of the anti-HSV-1 activity remaining in serum after non-radioactive 1C3 inoculation. A very rapid disappearance of the compound from the blood was observed since only 5.9 - 0.9 % of the radioactivity of the initially administered [ (3)H]-1C3 appeared in the plasma between 5-300 minutes after administration. A transient peak of radioactivity was detected in the kidney 15 minutes after inoculation. The bioassay confirms the presence of the compound circulating in a biologically active form up to 1 hour after injection.

Primary infection of mice with high titer inoculum respiratory syncytial virus: characterization and response to antiviral therapy

Intranasal infection of BALB/c mice with respiratory syncytial virus (RSV)-A2 (0.5 x 10(8) - 2.0 x 10(8) plaque-forming units, PFU) produced disease characterized by weight loss (2-3 g) and mortality (60%-100%) with the mean day of death ranging from 6-7 d after infection. The extent of RSV disease was inoculum titer-dependent and required a replication competent virus. Lung titers of virus peaked at 0.5-1 x 10(6) PFU/g wet weight. Bronchoalveolar lavage fluid (BALF) levels of IL-1beta, TNF-alpha, INF-gamma IL-12, IL-6, MIP-1alpha, RANTES, and protein were elevated, whereas IL-2, IL-4, IL-5, IL-13, and IL-10 were unchanged. Histological assessment of lungs revealed marked inflammatory pathology characterized by bronchiolitis, vasculitis, and interstitial pneumonia. Whole-body plethysmography revealed significant disease-associated deficits of respiratory function. Therapy with ribavirin administered either by the intranasal, subcutaneous, or oral route significantly reduced disease in a dose-dependent manner. Delaying the initiation of therapy resulted in a loss of activity for ribavirin. Synagis administered either intramuscularly as a single dose in prophylaxis or intranasally in prophylaxis, followed by therapy, also significantly reduced disease in a dose-dependent manner. Infection of mice with a high titer inoculum of RSV-A2 resulted in severe and fatal pulmonary disease that was responsive to treatment. This model may be useful to characterize the in vivo activity of experimental therapies for RSV infection.

Biologic properties of dengue viruses following serial passage in primary dog kidney cells: studies at the University of Hawaii.

Serial passage at low dilution of seven different wild-type dengue (DEN) viruses into primary dog kidney (PDK) cell cultures placed selective pressure that resulted in the following changes from parental phenotype: smaller plaques in LLC-MK2 cells, absent plaque formation in green monkey kidney cells, lack of a cytopathic effect in LLC-MK2 cells, shut-off of virus replication at high temperatures (temperature sensitivity), reduced virulence for rhesus monkeys manifested by reduced or absent viremia and/or absence of a secondary-type antibody response following homotypic challenge, and progressive increase in the mean day of death following intracerebral inoculation of sucking mice. Two DEN-1 strains showed most of these changes by the 15th PDK passage. Only one of two DEN-2 strains studied was carried to the 50th PDK passage at the University of Hawaii. For the latter strain, both the temperature of viral replicative shutoff and mouse neurovirulence were reduced. Three DEN-4 strains showed similar late-passage biologic marker changes. The observations made, although not exhaustive, provide laboratory correlates for virus strains that have shown reduced virulence but retained immunogenicity in humans. Candidate human vaccines have been prepared from five of the studied strains: DEN-1 (16007) at PDK 13, DEN-2 (16681 and S-16803) at PDK 50 or above, and DEN-4 (1036 and 341750) at PDK 48 and 20, respectively.

Effect of 5-Iodo-2′-Deoxyuridine on Vaccinia Virus (Orthopoxvirus) Infections in Mice

There is a concern that there may be unregistered stocks of smallpox that can be used for bioterrorism or biological warfare. According to the WHO Advisory Committee on Variola Research, there is a need to develop strategies to treat smallpox infections should they reappear. It would also be important to have an effective drug at hand for the treatment of monkeypox disease in humans. We show here that 5-iodo-2'-deoxyuridine (IDU) is a potent inhibitor of vaccinia virus (VV) replication and that IDU inhibits VV DNA synthesis in a dose-dependent way. The in vivo protective effect of IDU was assessed in the VV tail lesion model in immunocompetent mice and in a lethal model for VV infection in SCID (severe combined immune deficiency) mice that had been infected either intranasally, intraperitoneally, or intravenously. Subcutaneous treatment with IDU at 150 and 100 mg/kg of body weight markedly reduced the number of tail lesions in immunocompetent NMRI mice. Untreated intranasally VV-infected SCID mice died at 20.8 +/- 3.1 days after infection (mean +/- standard deviation). Treatment with IDU (subcutaneously, 150 mg/kg/day [from day 0 to 4] and 75 mg/kg/day [from day 6 to 11]) delayed-virus induced mortality by 15 days (mean day of death +/- standard deviation, 35.8 +/- 6.7; P < 0.0001). This protective effect was associated with (i) an improvement of lung histology and (ii) a marked reduction in lung viral titers. IDU also delayed VV-induced mortality when mice had either been infected intraperitoneally or intravenously. Even when the start of treatment with IDU (in intraperitoneally VV-infected mice) was postponed until 2 or 4 days after infection, an important delay in virus-induced mortality was noted.

Cytomegalovirus infection in immunocompromised guinea pigs: A model for testing antiviral agents in vivo

An experimental model for testing antiviral agents against severe cytomegalovirus (CMV) infection in immunocompromised hosts was developed. The model consisted of cyclophosphamide (Cy) treatment of CMV-infected guinea pigs to simulate CMV infection in immunodeficient individuals. Of the 3 Cy regimens tested, a single 300 mg/kg dose administered one day after virus inoculation resulted in the most severe CMV infection considering mortality rates, mean day of death and loss of body weight. Evaluation of responses to both T and B cell mitogens suggested that the severe and lethal CMV infection resulted from the combined immunosuppressive effect of Cy and CMV. The nucleoside analog [9-(1-3-dihydroxy-2-propoxymethyl)guanine (DHPG) was used to assess the usefulness of the CMV-infected immunocompromised host model. DHPG (100 mg/kg/day for 8 days) prevented death but did not reduce virus infectivity titers in blood of Cytreated, CMV-infected guinea pigs. This model of CMV infection in immunocompromised guinea pig is a relevant and convenient experimental tool for the assessment of candidate anti-CMV agents under well-defined experimental conditions, such as appropriate CMV inoculum and Cy regimen.

Therapeutic effect of the antiviral agent ribavirin in Junín virus infection of primates.

In order to assess the effect of the antiviral Ribavirin on the course of Junín virus infection in Callithrix jacchus, seven inoculated monkeys were treated with 15 mg of the drug, twice a day, starting 6 days after infection when all animals were viremic. The three untreated controls showed typical signs of Junín virus infection at 14 days pi and their mean time of death was 18 days. In contrast, no signs of illness were detected in Ribavirin-treated animals until 24 days pi, when marmosets showed signs of neurological involvement: 5 of these animals died (mean day of death: 36) but the two remaining treated monkeys improved and survived infection without sequelae. The comparison of survival rates (0% vs 28%) and the delay of the mean day of death observed indicates that the Ribavirin treatment used has therapeutic effect on Junín virus infection in vivo.

Effect of selenazofurin on influenza A and B virus infections of mice

The inhibitory effects of selenazofurin and ribavirin on influenza A and B virus infections in mice were compared. Both compounds, when administered intraperitoneally (i.p.), reduced lung consolidation and prolonged mean day of death, but ribavirin more effectively increased survivor number and lowered lung viral hemagglutinin (HA) titers. Lung HA titers often increased in selenazofurin-treated animals. To determine the most appropriate i.p. treatment schedule, influenza A virus-infected mice were treated once, twice or thrice daily for 7–9 days, or once only. Treatment once daily for 9 days beginning 4 h pre-virus exposure, for 3 days beginning 24 h post-virus exposure, or once only 48 h post-virus exposure was most effective. Body temperature, which usually declined during infection, increased to near-normal levles in animals treated with selenazofurin, especially in animals treated a single time or for 3 days with high dose levels. Selenazofurin was well tolerated at a dose of 50 mg/kg administered twice daily, and at 400 mg/kg administered once only. Rectal temperatures temporarily declined following every other day treatment with 400 mg/kg.

Efficacy of 5-methoxymethyl-2′-deoxyuridine in combination with arabinosyladenine for the treatment of primary herpes simplex genital infection of mice and guinea pigs

The relative efficacy of 5-methoxymethyl-2′-deoxyuridine (MMdUrd), arabinosyl-adenine (ara-A) and the combination of MMdUrd and ara-A in the treatment of experimental genital herpes (GH) was investigated using mouse and guinea pig models. The infection was initiated by intravaginal inoculation using either HSV-2, strain X-265 or HSV-2, strain MS. Treatment was initiated 3 h post virus inoculation. The parameters used to evaluate efficacy were: (i) percent mortality; (ii) mean day of death; (iii) virus yield from the vaginal secretions; and (iv) mean lesion score. The simultaneous application of 5% MMdUrd and 5% ara-A was an effective treatment for controlling primary GH in both animal models. Combination chemotherapy was also effective in preventing recurrence of infection as well as the emergence of drug resistant virus. At 20% concentration, ara-A was effective in providing protection against GH. However, lesions due to recurrent GH appeared after cessation of treatment and the virus isolated from vaginal secretions of ara-A treated animals required higher concentration of drug for inhibition of virus replication in cell culture. 20% MMdUrd was only partially effective in controlling GH. The production of infectious virus particles (virus yield) in cell culture after exposure to either ara-A of MMdUrd alone or in combination was determined. When MMdUrd and ara-A were used together, a substantially lower amount of each drug was needed to inhibit virus production completely and removal of drugs did not result in an increase in virus yield.

Effects of p-Aminobenzoic Acid, Methionine, Threonine and Protein Levels on Susceptibility of Mice to Plasmodium berghei

The effects of dietary p-aminobenzoic acid (PABA), protein, methionine and threonine on Plasmodium berghei infection in mice were investigated. Animals were fed diets containing 12 or 20% casein supplemented with PABA (0 or 2 mg/kg diet), methionine (0 or 15 mg/g casein) and threonine (0, 7.5, 27.5 or 47.5 mg/g casein). Percent mortality was lower in rats fed diets without PABA than in those fed diets containing PABA. All further experiments were conducted without supplemental PABA. While the mean day of death was greater in the groups fed 12% casein, percent mortality in these groups was nearly twofold higher than in the groups fed 20% casein. The presence or absence of 15 mg methionine per gram casein had no effect on percent mortality, mean day of death, or percent parasitemia, regardless of dietary casein level. Supplementation of threonine at any level to the 12% casein diet with supplemental methionine resulted in mortality rates similar to those from animals fed the 20% casein diets, but percent mortality was not altered by threonine in the absence of supplemental methionine. The mean day of death of animals fed 20% casein increased with increments of added threonine. Methionine had no influence on this phenomenon. It is concluded that the quantity of dietary protein and the quality of its amino acid composition can have profound effects on the susceptibility of mice to malaria.

Influenza type a virus infection of mice exposed in utero to chlordane; survival and antibody studies

Previous studies carried out by others have shown that in utero exposure of mice to chlordane effects a significant depression of cell-mediated immunity (CMI) at 100 days of life without adversely affecting the humoral immune system. In the studies reported herein we assessed the effect of in utero exposure to various doses of chlordane on the response of 38-day-old mice to influenza type A virus infection in terms of relative levels of mortality, mean day of death, and the levels of antiviral antibody in the primary and secondary immune response to the virus. In utero exposure to chlordane effected enhanced survival to influenza type A virus infection relative to mock-treated animals. No significant differences were noted in the mean day of death of chlordane-treated and mock-treated mice. A significant enhancement in the levels of antiviral antibody was noted in the chlordane-treated female mice but not male mice in both the primary and secondary immune response to the virus.

Plasmodium berghei: The effects of suppressor factor on vaccination

Suppressor factor-free known protective fractions (G, Sp2) extracted from Plasmodium berghei-infected erythrocytes were injected into groups of mice with and without suppressor factor (SF). One, two and three injections of SF did not significantly alter the mortality rate or the mean day of death of vaccinated animals. Peaks obtained during the preparation of SF, which were free of SF, were tested for protection. Peak three of this preparation, which is enhancing in the plaque cell test, gave no protection after three vaccinating injections, but 10 daily injections during infection did give significant protection. Three vaccinating injections of SF did not induce sufficient SF inhibitory response to alter the mean day of death or the mortality rate. The presence of SF in vaccine material probably does not greatly affect its protective activity since 10 injections of SF following infection were required to alter the response.

Immunomodulatory activity of isoprinosine on experimental viral infections in avian models

The immunomodulatory activity of Isoprinosine treatments have been experimentally verified on chicken infected by three different viruses: Newcastle disease, fowl plague and avian infectious bronchitis. In protection tests, positive variations in the mean day of death rather than in the mortality rate were found depending on the modality of treatment. A stimulatory influence on primary anti-Newcastle disease virus antibody response was observed. In the avian model the Isoprinosine antiviral effect appears as due mainly to the enhancement of interferon production and to a synergistic interferon-isoprinosine interaction.

Alterations in Influenza Virus Pulmonary Pathology Induced by Diethyl Ether, Halothane, Enflurane, and Pentobarbital Anesthesia in Mice

Three-week-old CD-1 mice infected with the PR-8 (mouse-adapted) strain of influenza virus while exposed to enflurane demonstrated a decrease in virus titers from the lungs of infected animals, less abnormality of lung histology, and an increase in survival in animals as compared with those receiving the other anesthetics tested. Greater than 90% mortality occurred in groups of mice which inhaled aerosolized virus and received no anesthesia, pentobarbital, diethyl ether, or halothane anesthesia 96 h following infection. Infected mice anesthetized with enflurane 96 h post-infection had significantly lower mortality rate (68%) when compared with the other groups. Halothane-anesthetized mice receiving intranasal influenza virus during anesthesia demonstrated increased survival and a delay in the mean day of death when compared with animals receiving either diethyl ether of pentobarbital anesthesia. Animals receiving enflurane during virus inoculation had an even lower mortality rate and a later mean day of death when compared with infected animals receiving day of the other three anesthetics. Examination of lungs from animals infected during anesthesia demonstrated influenza virus titers significantly less in the animals that received enflurane anesthesia when compared with the other groups. Histologic sections of lungs revealed extensive spread of the disease process into the alveoli and interstitium of the lungs of animals infected while receiving pentobarbital or diethyl ether anesthesia. Animals infected during halothane demonstrated pathologic characteristics similar to pentobarbital- and diethyl-ether-treated groups; however, the changes were not as extensive. Mice infected during exposure to enflurane revealed only a mild bronchopneumonia.

Effect of combinations of acyclovir with vidarabine or its 5'-monophosphate on herpes simplex viruses in cell culture and in mice.

The combination of various concentrations of acyclovir and vidarabine or its 5'-monophosphate usually produced an additive interaction with various strains of herpes simplex virus types 1 and 2 in Vero cells. Similarly, certain combinations of these drugs were more effective than the individual drugs in decreasing the mortality and increasing the mean day of death of mice inoculated intracerebrally with herpes simplex virus type 2. Neither antagonism nor interference was noted for any of the in vitro or in vivo combinations. The increased antiviral activity was determined not to be secondary to toxic effects of the drugs. Although viruses resistant to either vidarabine or acyclovir developed readily in cell culture, no evidence of cross-resistance was obtained. Furthermore, in the presence of the two drugs, mutants resistant to vidarabine, acyclovir, or vidarabine/acyclovir could not be isolated. These findings suggest that combinations with these antivirals, which are currently being evaluated singly for the therapy of severe forms of herpetic infection, could prove clinically useful if increasing numbers of resistant viral strains are observed.

Anti-herpesvirus activity of adenine arabinoside analogues in tissue culture and a genital infection of mice and guinea pigs

Four analogues of adenine arabinoside (ara-A) were compared for activity against herpes simplex virus (HSV) in tissue culture and in a genital infection of mice and guinea pigs. These analogues, 5′-monophosphate (ara-AMP), 5′-valerate ester (ara-AV), 2′,3′-diacetate ester (ara-ADA), and 2′,3′,5′-triacetate ester (ara-ATA) have greater water and lipid solubility and resistance to deamination than ara-A. In mouse embryo fibroblast cells, similar viral inhibitory levels were noted with ara-A, AMP, and ara-AV, while ara-ADA and ara-ATA were 6–10 times less active. In mice infected intravaginally with HSV type 2 (HSV-2), intravaginal treatment with 10% concentrations of each of the compounds beginning 3 h after viral challenge, had no effect on infection rates, titers of virus in vaginal secretions, mortality rates or the mean day of death as compared with placebo-treated controls. In the HSV-2 genital infection of guinea pigs, treatment with 10% vaginal creams or placebo vehicle was initiated 6 or 24 h after viral inoculation. In animals treated at 6 h with ara-A, ara-AMP and ara-AV, there was complete inhibition of viral replication in the vaginal tract and development of external genital lesions. When treatment with these three drugs was delayed 24 h after infection, there was no effect on vaginal virus titers, but lesion severity was reduced by ara-A or ara-AMP therapy. Ara-ATA was ineffective whether begun at 6 or 24 h. The greater solubility in water and lipid as well as the resistance to deamination of ara-AMP and ara-AV did not appear to enhance their antiviral activity over that of ara-A. Additionally, ara-ADA and ara-ATA exhibited less activity both in tissue culture and in the experimental genital infections.