Abstract 1009 Poster Session IV, Tuesday, 5/4 (poster 154)

In the United States the use of oral polio vaccine is associated with 4-5 cases of vaccine-associated paralytic poliomyelitis per year. In developing nations, despite eradication efforts, polio remains a severe threat. No therapy has been shown to be effective in the treatment of poliovirus (PV) infections of the central nervous system. Pleconaril is a novel antiviral agent which exhibits activity against a broad-spectrum of enteroviruses. The principle mechanism of action of this antiviral is through the inhibition of protein function associated with viral uncoating and attachment. We report the elimination of a revertant strain of PV type 2 (Sabin strain) (PV2S) from the cerebral spinal fluid (CSF) and serum of an immunodeficient infant using the novel antipicornaviral agent pleconaril.

A 4-month-old female admitted for evaluation of failure to thrive, hypotonia and decreased deep tendon reflexes was found to have severe combined immunodeficiency syndrome. Oral polio vaccine had been administered 2 days prior to admission. On day 6 post-vaccination CSF was examined for the presence of PV genome and virus using RT-PCR and viral culture, respectively. Using universal enteroviral primers targeted to the 5′ nontranslated region (5′NTR), a 204 bp fragment was amplified. The amplicon was cloned and sequenced. Sequence comparisons with those of the wild-type and vaccine strains of PV1-3 revealed that the amplified region of 5′NTR shared 99.4% identity with the sequence of PV2S. A single A to G transition, known to be associated with reversion to neurovirulence, was found at nucleotide 481 of PV2S; suggesting that the patient carried a neurovirulent strain. PV2S was subsequently cultured from the CSF.

Pleconaril, at a dose of 15 mg/kg/day p.o. was initiated, later increased to 22.5 mg/kg/day, and continued for a total of 16 days. Culture of CSF and serum while receiving therapy showed that the CSF became negative on day 6. PV genome was no longer detected in serum or CSF by RT-PCR at day 14. At 8 and 37 days post-treatment, no PV was found in CSF or serum. Pre and post-therapy stool isolates were assayed for the development of resistance to pleconaril. The inhibitory concentration-50% (IC50) to pleconaril was 1.9 and 1.4 µM, respectively; indicating that no change in sensitivity of PV2S to pleconaril occurred. Pleconaril appeared to be effective in the therapy of vaccine-acquired PV infection in this immunodeficient infant.