This study examined the effect of recent decline in malaria and increasing burden of neonatal admissions on the incidence of acute seizures, their proximate causes and phenotypes in children admitted to a rural hospital in Kenya. The burden of acute seizures in children remains high despite a reduction of malaria in the past decade. Indeed the overall incidence appeared to increase over the study period (2009–2013), as did the incidence of seizures attributable to malaria. The incidence of complex seizure increased the most (107 %). This suggests, in part, that causes of and risk factors for acute seizures are still prevalent in the community. Over 80 % of all incidence admissions resided less than 5 km from the KDH, implying hospital accessibility determines the admissions of acute seizures in this area. The most common causes of admissions with acute seizures were malaria and respiratory tract infections, but hypoglycemia, hypoxic-ischemic encephalopathy and neonatal sepsis were important among the neonates.
Changes in incidence of acute seizures
The incidence of acute seizures in this study (312 per 100,000/year) is lower than that reported in a previous study (425 per 100,000/year) [1], which used data on admissions during a time when malaria was a common cause of morbidity and mortality in this area. Despite the recent decline in malaria, our present data reveals that the incidence has been increasing between 2009 and 2013, an important epidemiological finding which is not apparent if the present incidence was compared with earlier years when incidence of malaria was high.
This increase in incidence was particularly observed for SAM, being highest for the complex seizure phenotypes; supporting increasing burden for acute seizures post the malaria decline era. There are three explanations for the increasing incidence of seizures following the earlier decline. First and most plausible, a reduction in malaria may have resulted in less exposure, thereby reducing the acquisition of naturally acquired immunity to malaria, resulting in more severe illness, including seizures, that requires hospitalisation [5]. Secondly, this could be related to proportional increase in neonatal causes of seizures such as hypoglycemia, sepsis and hypoxic-ischemic encephalopathy compared to an earlier study [1]. Finally, the increasing incidence of acute seizures could be related to possible improvements in health care services not measured in this study, which would encourage admissions.
Incidence of acute seizures
The incidence is grossly underestimated since only 28 % of it was from areas >5 kilometres. This suggests that poor infrastructure and transport costs may have resulted in some (if not most) seizures not being treated in hospital. In a recent study, only 56 % of persons with convulsive status epilepticus occurring with epilepsy were treated in KCH [17]. Other cultural reasons such as preference of traditional healers over biomedical practitioners may have contributed [18]. Despite the conservative incidence our estimates for prolonged and/or status epilepticus is higher than that reported in developed countries e.g. in London [19]. This may be explained by the high prevalence of infectious causes in this area e.g. malaria parasitemia, which was found in 36 % of all prolonged seizures; over 90 % of complex seizures in parasitemic children are caused by malaria [2]. Delays in management of acute seizures in peripheral clinics that may result in admission of seizures already refractory to treatment [14], adding to the high burden of prolonged seizures in this study.
Causes of acute seizures
Malaria remains the most important cause of admission with seizures, with malaria parasitemia observed in over a third of admissions. This proportion however is slightly less than that reported in previous studies in this area (>50 %) [1, 14], suggesting a possibility of emergence of other important causes of acute seizures particularly those common in the neonatal period. Falciparum malaria may cause seizures by: (i) sequestration-induced brain damage that manifests as seizures [20]; (ii) down-regulation of GABA receptors thereby increasing susceptibility to seizures [21]; (iii) metabolic complications such as hyponatremia or hypoglycaemia and; (iv) induction of inflammatory molecules that lower seizure threshold [22]. Susceptibility to seizures may be determined by genetic polymorphisms [13].
Hypoglycemia, unknown encephalopathy and neonatal sepsis, were more common in the neonates in greater proportions than in a previous study [1], yet some of these can be easily prevented and managed. It is however, unclear if a proportion of encephalopathy of unknown origin reflects neurotropic viruses that were not investigated in this study [23].
Malaria was more common in complex seizures compared to simple seizures, suggesting a causal role for these complex phenotypes, as demonstrated in previous studies [2]. Additionally, other causes of seizures were significantly more frequent in complex seizures, perhaps because it represents a severe phenotype of seizures, as supported by its association with increased mortality in this study and neurocognitive impairments in previous studies [24, 25]. However, gastroenteritis appeared to be more frequent in simple seizures compared to complex seizures as would be expected.
Changing phenotypes of acute seizures
Nearly half (46 %) of the admissions were complex seizures, a significant reduction from 70 % reported in previous studies in the same population [4, 13]. Since this phenotype is particularly attributable to malaria, the low frequency may be related to lower incidence of malaria during the study period compared to the early 2000s [5]. Complex seizures were associated with mean corpuscular volume, which may be a. marker of: (i) iron deficiency; (ii) red blood cell redistribution following sequestration into the deep capillary bends of the brain [26]; or (iii) presence of alpha thalassaemia [27].
Mortality in acute seizures
The mortality from acute seizures was greater than in previous studies (6 % vs. 3 %) [1], probably suggesting a change in aetiology related to increase in neonatal seizures, in which mortality was highest (10 %). Additionally, case fatality was common (12 %) of those with encephalopathy of unknown origin which could be important in the neonatal period. Future studies should screen for viral aetiology of acute seizures, which may be associated with mortality but were not assessed in this study [28].
In terms of causes of acute seizures, mortality was highest in malaria (20 %) and malnutrition (20 %). Control of malaria and prevention of malnutrition would reduce just under half of mortalities associated with acute seizures.
Strengths and limitations
These data were prospectively collected over a long time period with clinical and laboratory information documented in standardised proformas, thus findings are robust and reliable. Careful classification of acute seizures allowed objective relation of these phenotypes of seizures with causes, incidence and outcomes. These data may not represent the burden and situation of acute seizures in the community, since some seizures in this area are not treated at hospital. It was not possible to perform electroencephalography, owing to logistical constraints.