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Antimicrobial Agents and Chemotherapy, July 2006, p. 2409-2414, Vol. 50, No. 7
0066-4804/06/$08.00+0     doi:10.1128/AAC.00227-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Enteroviral Meningitis: Natural History and Outcome of Pleconaril Therapy

R. A. Desmond,1 N. A. Accortt,1,{dagger} L. Talley,2 S. A. Villano,3 S.-J. Soong,1 and R. J. Whitley4*

Department of Biostatistics and Bioinformatics, Medical Statistics Section, The University of Alabama at Birmingham, Birmingham, Alabama,1 Emmes Corporation, Rockville, Maryland,2 ViroPharma Incorporated, Exton, Pennsylvania,3 Department of Pediatrics, Microbiology, Medicine and Neurosurgery, The University of Alabama at Birmingham, Alabama4

Received 21 February 2006/ Returned for modification 21 April 2006/ Accepted 5 May 2006

Enteroviral meningitis causes appreciable morbidity in adults, including hospitalization, decreased activity, and headache. Limited data define the natural history of disease. No antiviral therapeutic agent has demonstrated improved outcome in controlled clinical trials. Pleconaril, an inhibitor of enterovirus replication, was tested in two placebo-controlled clinical trials. Of 607 randomized patients in a multicenter, double-blind placebo-controlled study of pleconaril (200 mg three times daily versus an identical-appearing placebo), 240 patients were confirmed to have enterovirus infection. The time to headache resolution was evaluated by using Kaplan-Meier survival methodology. A Cox regression model evaluated multivariate factors associated with disease resolution. Resolution of headache in patients with concomitant moderate to severe nausea at baseline occurred at a median of 9.5 days in the absence of therapy and was reduced to 7.0 days for pleconaril recipients (P = 0.009). For a headache score of >5 alone, treated patients resolved headache significantly more rapidly (P = 0.005). Males resolved headache 50% faster than females. Regardless of randomization group, patients with a baseline headache score of 5 or greater resolved headache 50% more slowly than patients with a baseline headache score of 4. No differences in either clinical or laboratory adverse events were noted. Over 50% of untreated patients had a persistent headache that was greater than 1 week in duration. Pleconaril shortened the course of illness compared to placebo recipients, especially in the early disease course. However, the benefit was achieved only modestly in a subgroup analysis of patients with more severe disease after adjusting for confounding variables.

* Corresponding author. Mailing address: CHB 303, 1600 Seventh Avenue South, Birmingham, AL 35233. Phone: (205) 934-5316. Fax: (205) 934-8559. E-mail: rwhitley{at}peds.uab.edu.

{dagger} Present address: Cancer Prevention Institute/Wright State University, Dayton, Ohio.

Antimicrobial Agents and Chemotherapy, July 2006, p. 2409-2414, Vol. 50, No. 7
0066-4804/06/$08.00+0     doi:10.1128/AAC.00227-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Simon, A, Schildgen, O, Schuster, F (2008). Viral infections in paediatric patients receiving conventional cancer chemotherapy. Arch. Dis. Child. 93: 880-889 [Abstract] [Full Text]  
  • Solomon, T., Hart, I. J, Beeching, N. J (2007). Viral encephalitis: a clinician's guide. PN 7: 288-305 [Abstract] [Full Text]  
  • (2006). Enteroviral Meningitis: Natural History and Treatment with Pleconaril. JWatch Infect. Diseases 2006: 6-6 [Full Text]  


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