Acute seizures attributable to falciparum malaria in an endemic area on the Kenyan coast

Falciparum malaria is an important cause of acute symptomatic seizures in children admitted to hospitals in sub-Saharan Africa, and these seizures are associated with neurological disabilities and epilepsy. However, it is difficult to determine the proportion of seizures attributable to malaria in endemic areas since a significant proportion of asymptomatic children have malaria parasitaemia. We studied children aged 0–13 years who had been admitted with a history of seizures to a rural Kenyan hospital between 2002 and 2008. We examined the changes in the incidence of seizures with the reduction of malaria. Logistic regression was used to model malaria-attributable fractions for seizures (the proportion of seizures caused by malaria) to determine if the observed decrease in acute symptomatic seizures was a measure of seizures that are attributable to malaria. The overall incidence of acute symptomatic seizures over the period was 651/100 000/year (95% confidence interval 632–670) and it was 400/100 000/year (95% confidence interval 385–415) for acute complex symptomatic seizures (convulsive status epilepticus, repetitive or focal) and 163/100 000/year (95% confidence interval 154–173) for febrile seizures. From 2002 to 2008, the incidence of all acute symptomatic seizures decreased by 809/100 000/year (69.2%) with 93.1% of this decrease in malaria-associated seizures. The decrease in the incidence of acute complex symptomatic seizures during the period was 111/100 000/year (57.2%) for convulsive status epilepticus, 440/100 000/year (73.7%) for repetitive seizures and 153/100 000/year (80.5%) for focal seizures. The adjusted malaria-attributable fractions for seizures with parasitaemia were 92.9% (95% confidence interval 90.4–95.1%) for all acute symptomatic seizures, 92.9% (95% confidence interval 89.4–95.5%) for convulsive status epilepticus, 93.6% (95% confidence interval 90.9–95.9%) for repetitive seizures and 91.8% (95% confidence interval 85.6–95.5%) for focal seizures. The adjusted malaria-attributable fractions for seizures in children above 6 months of age decreased with age. The observed decrease in all acute symptomatic seizures (809/100 000/year) was similar to the predicted decline (794/100 000/year) estimated by malaria-attributable fractions at the beginning of the study. In endemic areas, falciparum malaria is the most common cause of seizures and the risk for seizures in malaria decreases with age. The reduction in malaria has decreased the burden of seizures that are attributable to malaria and this could lead to reduced neurological disabilities and epilepsy in the area

Relationship between the population incidence of febrile convulsions in young children in Sydney, Australia and seasonal epidemics of influenza and respiratory syncytial virus, 2003-2010: a time series analysis

<p>Abstract</p> <p>Background</p> <p>In 2010, intense focus was brought to bear on febrile convulsions in Australian children particularly in relation to influenza vaccination. Febrile convulsions are relatively common in infants and can lead to hospital admission and severe outcomes. We aimed to examine the relationships between the population incidence of febrile convulsions and influenza and respiratory syncytial virus (RSV) seasonal epidemics in children less than six years of age in Sydney Australia using routinely collected syndromic surveillance data and to assess the feasibility of using this data to predict increases in population rates of febrile convulsions.</p> <p>Methods</p> <p>Using two readily available sources of routinely collected administrative data; the NSW Emergency Department (ED) patient management database (1 January 2003 - 30 April 2010) and the Ambulance NSW dispatch database (1 July 2006 - 30 April 2010), we used semi-parametric generalized additive models (GAM) to determine the association between the population incidence rate of ED presentations and urgent ambulance dispatches for 'convulsions', and the population incidence rate of ED presentations for 'influenza-like illness' (ILI) and 'bronchiolitis' - proxy measures of influenza and RSV circulation, respectively.</p> <p>Results</p> <p>During the study period, when the weekly all-age population incidence of ED presentations for ILI increased by 1/100,000, the 0 to 6 year-old population incidence of ED presentations for convulsions increased by 6.7/100,000 (P < 0.0001) and that of ambulance calls for convulsions increased by 3.2/100,000 (P < 0.0001). The increase in convulsions occurred one week earlier relative to the ED increase in ILI. The relationship was weaker during the epidemic of pandemic (H1N1) 2009 influenza virus.</p> <p>When the 0 to 3 year-old population incidence of ED presentations for bronchiolitis increased by 1/100,000, the 0 to 6 year-old population incidence of ED presentations for convulsions increased by 0.01/100,000 (P < 0.01). We did not find a meaningful and statistically significant association between bronchiolitis and ambulance calls for convulsions.</p> <p>Conclusions</p> <p>Influenza seasonal epidemics are associated with a substantial and statistically significant increase in the population incidence of hospital attendances and ambulance dispatches for reported febrile convulsions in young children. Monitoring syndromic ED and ambulance data facilitates rapid surveillance of reported febrile convulsions at a population level.</p

The incidence, aetiology and outcome of acute seizures in children admitted to a rural Kenyan district hospital

<p>Abstract</p> <p>Background</p> <p>Acute seizures are a common cause of paediatric admissions to hospitals in resource poor countries and a risk factor for neurological and cognitive impairment and epilepsy. We determined the incidence, aetiological factors and the immediate outcome of seizures in a rural malaria endemic area in coastal Kenya.</p> <p>Methods</p> <p>We recruited all children with and without seizures, aged 0–13 years and admitted to Kilifi District hospital over 2 years from 1^stDecember 2004 to 30^thNovember 2006. Only incident admissions from a defined area were included. Patients with epilepsy were excluded. The population denominator, the number of children in the community on 30^thNovember 2005 (study midpoint), was modelled from a census data.</p> <p>Results</p> <p>Seizures were reported in 900/4,921(18.3%) incident admissions and at least 98 had status epilepticus. The incidence of acute seizures in children 0–13 years was 425 (95%CI 386, 466) per 100,000/year and was 879 (95%CI 795, 968) per 100,000/year in children <5 years. This incidence data may however be an underestimate of the true incidence in the community. Over 80% of the seizures were associated with infections. Neonatal infections (28/43 [65.1%]) and falciparum malaria (476/821 [58.0%]) were the main diseases associated with seizures in neonates and in children six months or older respectively. Falciparum malaria was also the main illness (56/98 [57.1%]) associated with status epilepticus. Other illnesses associated with seizures included pyogenic meningitis, respiratory tract infections and gastroenteritis. Twenty-eight children (3.1%) with seizures died and 11 surviving children (1.3%) had gross neurological deficits on discharge. Status epilepticus, focal seizures, coma, metabolic acidosis, bacteraemia, and pyogenic meningitis were independently associated with mortality; while status epilepticus, hypoxic ischaemic encephalopathy and pyogenic meningitis were independently associated with neurological deficits on discharge.</p> <p>Conclusion</p> <p>There is a high incidence of acute seizures in children living in this malaria endemic area of Kenya. The most important causes are diseases that are preventable with available public health programs.</p

Sickness behaviour pushed too far – the basis of the syndrome seen in severe protozoal, bacterial and viral diseases and post-trauma

Certain distinctive components of the severe systemic inflammatory syndrome are now well-recognized to be common to malaria, sepsis, viral infections, and post-trauma illness. While their connection with cytokines has been appreciated for some time, the constellation of changes that comprise the syndrome has simply been accepted as an empirical observation, with no theory to explain why they should coexist. New data on the effects of the main pro-inflammatory cytokines on the genetic control of sickness behaviour can be extended to provide a rationale for why this syndrome contains many of its accustomed components, such as reversible encephalopathy, gene silencing, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia. It is thus proposed that the pattern of pathology that comprises much of the systemic inflammatory syndrome occurs when one of the usually advantageous roles of pro-inflammatory cytokines – generating sickness behaviour by moderately repressing genes (Dbp, Tef, Hlf, Per1, Per2 and Per3, and the nuclear receptor Rev-erbα) that control circadian rhythm – becomes excessive. Although reversible encephalopathy and gene silencing are severe events with potentially fatal consequences, they can be viewed as having survival advantages through lowering energy demand. In contrast, dyserythropoiesis, seizures, coagulopathy, hypoalbuminaemia and hypertriglyceridaemia may best be viewed as unfortunate consequences of extreme repression of these same genetic controls when the pro-inflammatory cytokines that cause sickness behaviour are produced excessively. As well as casting a new light on the previously unrationalized coexistence of these aspects of systemic inflammatory diseases, this concept is consistent with the case for a primary role for inflammatory cytokines in their pathogenesis across this range of diseases

Iron Deficiency and Acute Seizures: Results from Children Living in Rural Kenya and a Meta-Analysis

There are conflicting reports on whether iron deficiency changes susceptibility to seizures. We examined the hypothesis that iron deficiency is associated with an increased risk of acute seizures in children in a malaria endemic area