ACHIA

2003

CMV involving the CNS

Subject
Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial

Authors
N/A

Source
Journal of Pediatrics. 143(1):16-25, 2003 Jul.

N/A

Smallpox: a potential agent of bioterrorism. [Review] [40 refs]

Authors
N/A

Source
Antiviral Research. 57(1-2):7-12, 2003 Jan.

Abstract     
OBJECTIVE: To evaluate the efficacy and safety of ganciclovir therapy in neonates with congenital cytomegalovirus (CMV) disease. STUDY DESIGN: Neonates with symptomatic CMV disease involving the central nervous system were randomly assigned to receive 6 weeks of intravenous ganciclovir versus no treatment. The primary end point was improved brainstem-evoked response (BSER) between baseline and 6-month follow-up (or, for patients with normal baseline hearing, normal BSER at both time points). RESULTS: From 1991 to 1999, 100 patients were enrolled. Of these, 42 patients had both a baseline and 6-month follow-up BSER audiometric examination and thus were evaluable for the primary end point. Twenty-one (84%) of 25 ganciclovir recipients had improved hearing or maintained normal hearing between baseline and 6 months versus 10 (59%) of 17 control patients (P=.06). None (0%) of 25 ganciclovir recipients had worsening in hearing between baseline and 6 months versus 7 (41%) of 17 control patients (P<.01). A total of 43 patients had a BSER at both baseline and 1 year or beyond. Five (21%) of 24 ganciclovir recipients had worsening of hearing between baseline and > or =1 year versus 13 (68%) of 19 control patients (P<.01). A total of 89 patients had absolute neutrophil counts determined during the course of the study; 29 (63%) of 46 ganciclovir-treated patients had grade 3 or 4 neutropenia treatment versus 9 (21%) of 43 control patients (P<01). CONCLUSIONS: Ganciclovir therapy begun in the neonatal period in symptomatically infected infants with CMV infection involving the central nervous system prevents hearing deterioration at 6 months and may prevent hearing deterioration at > or =1 year. Almost two thirds of treated infants have significant neutropenia during therapy.

Pleconaril in infants with enterovirus meningitis

Subject
Double blind placebo-controlled trial of pleconaril in infants with enterovirus meningitis

Authors
N/A

Source
Pediatric Infectious Disease Journal. 22(4):335-41, 2003 Apr.

Abstract     
BACKGROUND: Enterovirus (EV) meningitis is common in infants and may have neurologic complications.  Treatment of older children and adults with pleconaril has been associated with reduced severity and duration of symptoms. This study evaluated the pharmacokinetics, safety and efficacy of pleconaril in infants with EV meningitis.  METHODS: Infants < or =12 months old with suspected EV meningitis were randomized 2:1 to receive pleconaril, 5 mg/kg/dose orally three times a day or placebo for 7 days. Evaluations included pharmacokinetic determinations, safety laboratory testing, serial culture and PCR assays and clinical evaluations. RESULTS: Of 21 evaluable subjects 20 were confirmed with EV infection (12 pleconaril, 8 placebo). Among pleconaril-treated subjects 26 of 29 peak and trough pleconaril levels exceeded the 90% inhibitory concentration for EVs. A median 3.5-fold drug accumulation occurred between Days 2 and 7. Pleconaril was well-tolerated, although twice as many adverse events occurred per subject in the pleconaril group. Serial cultures from the oropharynx, rectum and serum had low yield (< or =50%) and positivity generally persisted for <4 days No significant differences in duration of positivity by culture or PCR, hospitalization or symptoms were detected between groups. CONCLUSIONS: The dose of pleconaril studied provided sufficient plasma levels and was well-tolerated; however, drug accumulation was evident. The low yields of serial viral cultures, relatively short and benign clinical courses and the small number of subjects enrolled precluded demonstration of efficacy. If this medication is to be prescribed in infants, surveillance for toxicity related to drug accumulation will be necessary.

Smallpox: a potential agent of bioterrorism

Subject
Smallpox: a potential agent of bioterrorism. [Review] [40 refs]

Authors
N/A

Source
Antiviral Research. 57(1-2):7-12, 2003 Jan.

Abstract     
The events of 11 September 2001, in New York City, and subsequent identification of anthrax in the United States Postal System, have generated a new sense of awareness for the potential of biological terrorism, if not warfare.  Among those agents identified by the Centers for Disease Control and Prevention as 'Class A Bioterrorist Threats', smallpox is among the most dangerous. The ease of transmission of this agent, the lack of immunity in the population at large to this agent, and rapidity of its spread, if released, all generate significant concern for its deployment. A vaccine directed against smallpox is available but it is also associated with significant adverse events-some of which are life-threatening. Further, no antiviral drug has proven efficacious for therapy of human disease, although one licensed drug, Cidofovir, does have in vitro activity. Regardless, heightened awareness should lead to the development of a vaccine without significant adverse events and safe and efficacious antiviral drugs. The availability of a vaccine and antiviral drugs that are safe would significantly remove any major threat of smallpox deployment by a terrorist.