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Original article

Pleconaril revisited: clinical course of chronic enteroviral meningoencephalitis after treatment correlates with in vitro susceptibility

Joanne G Wildenbeest, Peterhans J van den Broek, Kimberley SM Benschop, Gerrit Koen, Peter C Wierenga, Ann CTM Vossen, Taco W Kuijpers, Katja C Wolthers

Corresponding author name: Joanne G Wildenbeest
Corresponding author e-mail: j.g.wildenbeest@amc.uva.nl

Citation: Antiviral Therapy 2012; 17:459-466
doi: 10.3851/IMP1936

Date accepted: 10 July 2011
Date published online: 24 October 2011

Abstract

Background: Human enteroviruses (HEVs) can cause severe infections, especially in patients with a deficient humoral immune response, such as X-linked agammaglobulinemia. In this patient group, chronic enteroviral meningitis (CEMA) is feared because of extensive morbidity and high fatality rate. Treatment options consist of intravenous immunoglobulin (IVIG), with various outcomes. Pleconaril is an antiviral agent with in vitro activity against HEVs that has been used in the treatment of HEV infections.

Methods: The efficacy of pleconaril and IVIG against HEV isolated from the patients was assessed in vitro in two patients with CEMA.

Results: Echovirus 11 was found in the cerebrospinal fluid (CSF) of case 1. Treatment with high-dose IVIG and pleconaril did not provide any clinical improvement and HEV PCR in CSF remained positive. Case 2 (echovirus 13 positive in CSF) was also treated with IVIG and pleconaril. The patient recovered completely and HEV PCR in CSF became negative. Recent IVIG batches contained low titres of neutralizing antibodies against the patient strains. Echovirus 11 (case 1) was resistant to pleconaril in vitro, whereas echovirus 13 (case 2) was susceptible, in accordance with virological response after treatment and subsequent clinical results.

Conclusions: This is the first report that evaluates efficacy of antiviral treatment in CEMA patients in relation to in vitro susceptibility of clinical virus isolates. Since pleconaril is no longer available for compassionate use we strongly propagate that new drugs should be developed against these potential life threatening HEV infections.

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