title: Topical treatment of cutaneous vaccinia virus infections in immunosuppressed hairless mice with selected antiviral substances.
abstract: BACKGROUND
  Certain nucleoside, nucleotide and pyrophosphate analogues may be useful for treating severe complications arising as a result of virus dissemination following smallpox (live vaccinia virus) vaccinations, especially in immunocompromised individuals. We used an immunosuppressed hairless mouse model to study the effects of 10 antiviral agents on progressive vaccinia infections.
  
  
  METHODS
  Hairless mice were immunosuppressed by treatment with cyclophosphamide (100 mg/kg) every 4 days starting 1 day prior to vaccinia virus (WR strain) infection of wounded skin. Topical treatments with antiviral agents were applied twice a day for 7 days starting 5 days after virus exposure.
  
  
  RESULTS
  Topical 1% cidofovir cream treatment was effective in significantly reducing primary lesion severity and decreasing the number of satellite lesions. Topical 1% cyclic HPMPC and 1% phosphonoacetic acid were not quite as active as cidofovir. Ribavirin (5%) treatment reduced lesion severity and diminished the numbers of satellite lesions, but the mice died significantly sooner than placebos. 2-Amino-7-[(1,3,-dihydroxy-2-propoxy)methyl]purine (compound S2242; 1%) moderately reduced primary lesion sizes. Ineffective treatments included 5% arabinosyladenine, 1% arabinosylcytosine, 1% 5-chloro-arabinosylcytosine, 5% arabinosylhypoxanthine 5-monophosphate and 5% viramidine.
  
  
  CONCLUSIONS
  Of the compounds tested, topically applied cidofovir was the most effective treatment of cutaneous vaccinia virus infections in immunosuppressed mice. Topical treatment with cidofovir could be considered as an adjunct to intravenous drug therapy for serious infections.
authors.affiliation: Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, UT, USA. don.smee@usu.edu
authors.forename: Donald F
authors.initials: DF
authors.lastname: Smee
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Bailey
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Wong
authors.forename: E Bart
authors.initials: EB
authors.lastname: Tarbet
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D000077404:Cidofovir; D003520:Cyclophosphamide / Q000737:chemistry / Q000494:pharmacology*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D051379:Mice; D008812:Mice, Hairless; D008826:Microbial Sensitivity Tests; D063065:Organophosphonates / Q000737:chemistry / Q000494:pharmacology*; D011687:Purines / Q000737:chemistry / Q000494:pharmacology*; D017193:Skin Diseases, Viral / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D014615:Vaccinia / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D014616:Vaccinia virus / Q000187:drug effects* / Q000276:immunology / Q000302:isolation & purification
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D011687:Purines; C092709:S 2242; D003596:Cytosine; D003520:Cyclophosphamide; D000077404:Cidofovir