Abstract
Background
 In malaria endemic areas, where up to 70% of children have peripheral parasitaemia, it is unclear why some children develop seizures. Human herpes viruses are common causes of febrile seizures. We investigated the hypothesis that seizures in children admitted to hospital are caused by concomitant human herpes virus infections.
 Methods
 We examined the presence of parasitaemia in plasma and viruses in cerebrospinal fluid (CSF) of 100 children with acute symptomatic seizures (84% with complex acute symptomatic seizures (focal, repetitive or prolonged)) and in 45 children without seizures using polymerase chain reaction. The analysis compared the distribution of human herpes virus between children with acute symptomatic seizures and those without these seizures by computing odds ratios using a logistic regression accounted for potential confounders.
 Results
 Human herpes viruses 6 & 7 were found in the CSF of 22% of children with acute symptomatic seizures and in 24% of those without seizures, and overall, there was no association with acute symptomatic seizures ((adjusted odds ratio (OR)=1.48 (95%CI, 0.54-4.05), p=0.448) nor complex acute symptomatic seizures (OR=2.34 (95%CI, 0.92-5.97), p=0.075). Human herpes virus 7 was significantly associated with complex acute symptomatic seizures (OR=8.80 (95%CI, 1.20-64.84), p=0.033), while herpes virus 6 was not (OR=1.71 (95%CI, 0.55-5.30), p=0.351). The logistic regression model with significant association for human herpes virus 7 and complex acute symptomatic seizures accounted for falciparum malaria, malnutrition and CSF protein levels, whose inclusion effect modified the OR of a baseline model by 81%.
 Conclusions
 Human herpes virus 7 but not 6 is associated with common complex acute symptomatic seizures in a malaria endemic area in Kenya. Viruses should be screened in children admitted with acute symptomatic seizures.
Highlights
Acute symptomatic seizures are a common presentation in children admitted to hospitals in sub-Saharan Africa[1]
Human herpes viruses (HHV) 6 was found in the cerebrospinal fluid (CSF) of 19% of 145 children with encephalopathy, while HHV 7 was found in 7%
HHV 7 was associated with complex acute symptomatic seizures, but not with all acute symptomatic seizures, in a model accounting for falciparum malaria, malnutrition and CSF protein levels
Summary
Acute symptomatic seizures are a common presentation in children admitted to hospitals in sub-Saharan Africa[1]. Because the prevalence of asymptomatic parasitaemia in the community is high (up to 70%) in these areas[4], other childhood illnesses (e.g. viral or bacterial) may be important causes of acute symptomatic seizures, with the presence of malaria parasitaemia being coincidental. We showed through modelling that about 10% of acute symptomatic seizures in malaria may be attributable to other illnesses[2], which may include central nervous system (CNS) infections with viruses and bacteria. Acute symptomatic seizures in malaria-endemic areas are likely to be related to direct brain involvement, e.g. sequestration of P. falciparum parasites[2], but may be caused by a concomitant viral infection, as documented in previous studies[7,8]
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