Use of 5-Iodo-2'-Deoxyuridine (IDU) in Treatment of Herpes Simplex Keratitis

Kaufman, Herbert E.; Martola, Eeva-Liisa; Dohlman, Claes H.

doi:10.1001/archopht.1962.00960030239015

Cited by 235 publications

(57 citation statements)

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“…Fiala et al (6) showed that ara-C was more active than ara-A, and IdUrd was less active for several strains of HSV-2 in WI-38 cells. These studies were extended by Marks (22), who showed that IdUrd was somewhat less (12), and later in clinical keratitis (15). In addition, it has been shown that IdUrd in dimethyl sulfoxide is effective when applied topically to HSV infections of guinea pig skin (35) and in man (21).…”

Section: Discussionmentioning

confidence: 94%

Chemotherapy of Genital Herpes Simplex Virus Type 2 Infections of Female Hamsters

Renis

1977

Antimicrob Agents Chemother

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The antiviral activity of 1-,3-n-arabinofuranosylcytosine (ara-C, cytarabine, Cytosar), 5-iodo-2'-deoxyuridine (IdUrd), 9-,8-D-arabinofuranosyladenine (ara-A), and disodium phosphonoacetate (PAA) have been compared in herpes simplex virus type 2 (HSV-2)-infected primary rabbit kidney cells and in female hamsters with genital HSV-2 infection. In vitro, ara-C and IdUrd were more active than ara-A, and PAA was least active. In female hamsters with genital HSV-2 infection, intravaginal treatment with PAA or ara-A was more effective than either ara-C or IdUrd. PAA was more active than ara-A when treatment was initiated early (1 h) after infection. The activity of PAA was greatly reduced if initiation of treatment was delayed for 24 h. Both PAA and ara-A reduced the virus titers of the vagina and protected hamsters from death when the drugs were given by either the intravaginal or subcutaneous route, with intravaginal treatment being more effective.Genital herpesvirus infections, primarily caused by herpes simplex virus type 2 (HSV-2), are transmitted by venereal contact (9, 26). The infection can be painful and recurrent. If lesions are present late during the gestation period, the neonate is at high risk, resulting in disease with high morbidity and mortality (25). Furthermore, HSV-2 has been implicated in the etiology of cervical carcinoma (2,4,23).At the present time, there is no effective treatment for genital HSV infections. However, several agents with antiherpes activity in other systems have been studied in herpes genitalis. Topical application of certain heterocyclic dyes, followed by exposure to light, has been proposed as a method for treating this disease (5). However, in subsequent studies with proflavine (34), or in a double-blind study with neutral red (24), it was not possible to demonstrate efficacy.We have recently described the experimental genital infection of female hamsters with HSV-2 (30). In the studies described herein, several drugs with reported antiherpes activity have been compared in vitro and in female hamsters with genital HSV-2 infection. MATERIALS AND METHODSVirus. Stocks of HSV-2 (strain 35D) were supplied by L. T. Chien, University of Tennessee. The virus had a titer of 7.5 x 105 to 1.0 x 0l plaque-forming units per 0.5 ml on primary rabbit kidney monolayers.In vitro antiviral activity. Contiguous monolayers of primary rabbit kidney cells were infected by incubating 0.5 ml of stock virus with drained monolayers (60-mm plastic petri dishes, Falcon) for 60 min at 370C. The monolayers were washed and refed with 4.5 ml of Eagle medium containing 3% fetal bovine serum. The drugs were prepared in Hanks solution, and 0.5 ml of the appropriate dilution was added to each plate, resulting in the concentrations indicated. The cultures were harvested to -70°C when approximately 50 to 75% of the cells in the control cultures showed evidence of cytopathology. The virus titers of the frozen-thawed cultures were determined by the plaque method on rabbit kidney monolayers.Genital infection of femal...

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Section: Discussionmentioning

confidence: 94%

Chemotherapy of Genital Herpes Simplex Virus Type 2 Infections of Female Hamsters

Renis

1977

Antimicrob Agents Chemother

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“…To date, however, progress has been limited to direct treatment of the herpetic lesion. Currently available antivirals, idoxuridine (7,8,9), trifluorothymidine (11), and arabinosyl adenine (1), cause reductions in both the severity of ocular infection and the duration of virus shedding in the tear film. They do not prevent the establishment of latency or alter the incidence of recurrent disease (3,12).…”

Section: Discussionmentioning

confidence: 99%

Quantitation of herpes simplex virus type 1 shed in preocular tear film of rabbits treated with acyclovir

Green¹,

Dunkel²,

Morris³

1981

Antimicrob Agents Chemother

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The quantity and duration of herpes simplex virus type 1 shedding in the preocular tear film of rabbits were measured before, during, and after administration of acyclovir topically, intravenously, and by both of these routes. Topical administration reduced shedding significantly. Intravenous administration was without effect and in the combination regimen added nothing to the effectiveness of local application. This study was designed (i) to compare acyclovir treatment modalities; (ii) to determine the titer of virus shed in the preocular tear film of rabbits before, during, and after acyclovir therapy; and (iii) to correlate virus shedding with other clinical parameters of ocular herpetic infection.MATERIALS AND METHODS Inoculation. Forty-eight New Zealand albino rabbits were bilaterally inoculated with 106 plaque-forming units of McKrae strain HSV type 1 (HSV-1). Virus samples (100 pl each) in Hanks balanced salt solution (GIBCO Laboratories) were instilled onto unscarified corneas, the lids were closed, and the globes were massaged for 15 s. On day 3 post-inoculation, all animals were examined by slit lamp microscopy and placed into four balanced groups (12 animals per group) with matched corneal and conjunctival involvement.Treatment. Treatment of experimental and control groups was initiated on day 3 post-inoculation and continued through day 18 post-inoculation. Treatment group A received ocular instillation of a 3-mm ribbon of 3% acyclovir ointment in the lower conjunctival culde-sac three times per day (6:00 a.m., 1:00 p.m., and 8:00 p.m.). Treatment group B received daily marginal ear vein injections of acyclovir sodium salt (50 mg/kg in 5 ml of sterile saline). Treatment group C received combined therapy of topical instillation of acyclovir ointment three times per day and marginal ear vein injections of acyclovir sodium salt (50 mg/kg in 5 ml of sterile saline). Control group D received ocular instillation of a 3-mm ribbon of placebo ointment (petrolatum base) three times per day.Daily evaluation. A 100-pl amount of a 5% methylene blue solution in phosphate-buffered saline was dropped onto each cornea. Corneal involvement was graded by slit lamp microscopy on a scale of 0 to 4+: 0, no punctate lesions or dendritic figures present; 1+, 25% involvement of corneal surface with dendritic figures; 2+, 50% involvement; 3+, 75% involvement; and 4+, 100% involvement (geographic figure). Conjunctivitis was also graded on a scale of 0 to 4+.Measurement of virus in tear film. Virus shedding was monitored by culture of the preocular tear film of all groups. Cotton-tipped swabs were passed over the upper and lower conjunctival cul-de-sac, lightly rolled over the corneal epithelium, and retained in the nasal fornix for 5 to 10 s for maximum tear film absorption (18). Swabs were eluted by agitation for 15 s. Samples of 50 p1 were adsorbed onto confluent 16-mm Vero cell monolayers for 10 min at 37°C in 5% CO2. Cultures were reconstituted with 0.5 ml of minimum essential medium containing 5% fetal bovine serum (GIBCO...

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“…Antiviral agents were first successfully administered to patients in the 1960s, when Bauer prevented disease by giving thiosemicarbazone (methisazone) to patients exposed to smallpox (20) and Kaufman greatly improved the healing of herpes keratitis by treating patients with topical idoxuridine (233 (460). Two drugs that illustrate this well are idoxuridine (5-iodo-2'-deoxyuridine) and trifluorothymidine (5-trifluoromethyl-2'-deoxyuridine) (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…When administered systemically to patients, however, it did not decrease the risk of death from herpes encephalitis and it caused myelosuppression in almost all patients who received it (40). On the other hand, the drug was effective and much less toxic when administered topically to patients with herpes keratitis (233). It is still used for this purpose.…”

Section: Introductionmentioning

confidence: 99%

Antiviral therapy: current concepts and practices

Bean

1992

Clin Microbiol Rev

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Drugs capable of inhibiting viruses in vitro were described in the 1950s, but real progress was not made until the 1970s, when agents capable of inhibiting virus-specific enzymes were first identified. The last decade has seen rapid progress in both our understanding of antiviral therapy and the number of antiviral agents on the market. Amantadine and ribavirin are available for treatment of viral respiratory infections. Vidarabine, acyclovir, ganciclovir, and foscarnet are used for systemic treatment of herpesvirus infections, while ophthalmic preparations of idoxuridine, trifluorothymidine, and vidarabine are available for herpes keratitis. For treatment of human immunodeficiency virus infections, zidovudine and didanosine are used. Immunomodulators, such as interferons and colony-stimulating factors, and immunoglobulins are being used increasingly for viral illnesses. While resistance to antiviral drugs has been seen, especially among AIDS patients, it has not become widespread and is being intensely studied. Increasingly, combinations of agents are being used: to achieve synergistic inhibition of viruses, to delay or prevent resistance, and to decrease dosages of toxic drugs. New approaches, such as liposomes carrying antiviral drugs and computer-aided drug design, are exciting and promising prospects for the future.

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Use of 5-Iodo-2'-Deoxyuridine (IDU) in Treatment of Herpes Simplex Keratitis

Cited by 235 publications

References 2 publications

Chemotherapy of Genital Herpes Simplex Virus Type 2 Infections of Female Hamsters

Chemotherapy of Genital Herpes Simplex Virus Type 2 Infections of Female Hamsters

Quantitation of herpes simplex virus type 1 shed in preocular tear film of rabbits treated with acyclovir

Antiviral therapy: current concepts and practices

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