Date of Graduation

8-14-2010

Degree Type

Capstone Project

Degree Name

Master of Science in Physician Assistant Studies

First Advisor

Mary Von PA-C, MS, DFAAPA

Second Advisor

Annjanette Sommers MS, PAC

Third Advisor

Rob Rosenow PharmD, OD

Abstract

Background: Cerebral malaria is a severe neurological form of malaria that affects the central nervous system, is caused by Plasmodium falciparum parasitemia, and has a common complication of seizures and coma especially in children. In African children under the age of 5 it is the leading cause of death; over one million children in sub-Saharan Africa alone die or are disabled as a result of cerebral malaria annually. Seizures are a frequent complication of cerebral malaria and are associated with an increased risk of death and neurological sequelae including epilepsy, as well as a much broader range of motor and cognitive impairments. These impairments severely impact a child’s lifelong educational and social potential. Phenobarbital is an effective anti-convulsant that both controls and prevents seizures, is widely available in resource poor countries and can be delivered in a single IM dose for ease of rapid delivery. The objective is to assess the efficacy of phenobarbital when given as anti-convulsant prophylaxis in children with cerebral malaria.

Methods: An exhaustive search of available medical literature was performed using CINAHL, MEDLINE, Cochrane Database, and the African Index Medicus. The search terms included “cerebral malaria”, “children”, “Phenobarbital”, “prophylaxis” and “seizure”. All full text articles in the English language were used. Meta-analysis and case studies were excluded. Three articles were chosen for review.

Results: Overall it was found in all the studies that the prophylactic use of phenobarbital (PB) in children with cerebral malaria decreased the number of prolonged seizures they had while in the acute stage of parasitemia. It was also found that malaria treatment with quinine does not potentiate or interact with the PB, and that PB does not prolong coma or delay the recovery of children with cerebral malaria, nor does PB have any long term negative cognitive effects in children. However, the dose and route of administration of PB in children remains a controversy. One study that suggested that PB 20mg/kg intramuscularly was effective, but the children in this study receiving treatment had a mortality rate double the control group, likely due to anti-convulsant polypharmacy. Another study recommended 10mg/kg IM dosing but it was found to not be effective in controlling seizures. One study showed that 15mg/kg intravenously was effective, and a parallel simulated study recommended that the same dose given IM would be just as effective, although there is no actual data to support this.

Conclusion: The use of phenobarbital as a prophylactic anti-convulsive in children that have cerebral malaria is an effective way of decreasing acute seizure activity and therefore reducing the risk of long term neurological sequelae in this population. Standardized dosing and route of administration of phenobarbital for this application have not yet been established however, and more randomized controlled trials need to be completed before recommendations can be made.

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