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1.  Accuracy of clinical stroke scores for distinguishing stroke subtypes in resource poor settings: A systematic review of diagnostic test accuracy 
Background:
Stroke is the second leading cause of death globally. Computerized tomography is used to distinguish between ischemic and hemorrhagic subtypes, but it is expensive and unavailable in low and middle income countries. Clinical stroke scores are proposed to differentiate between stroke subtypes but their reliability is unknown.
Materials and Methods:
We searched online databases for studies written in English and identified articles using predefined criteria. We considered studies in which the Siriraj, Guy's Hospital, Besson and Greek stroke scores were compared to computerized tomography as the reference standard. We calculated the pooled sensitivity and specificity of the clinical stroke scores using a bivariate mixed effects binomial regression model.
Results:
In meta-analysis, sensitivity and specificity for the Siriraj stroke score, were 0.69 (95% CI 0.62-0.75) and 0.83 (95% CI 0.75-0.88) for ischemic stroke and 0.65 (95% CI 0.56-0.73) and 0.88 (95% CI 0.83-0.91) for hemorrhagic stroke. For the Guy's hospital stroke score overall sensitivity and specificity were 0.70 (95% CI 0.53-0.83) and 0.79 (95% CI 0.68-0.87) for ischemic stroke and 0.54 (95% CI 0.42-0.66) and 0.89 (95% CI 0.83-0.94) for hemorrhagic stroke.
Conclusions:
Clinical stroke scores are not accurate enough for use in clinical or epidemiological settings. Computerized tomography is recommended for differentiating stroke subtypes. Larger studies using different patient populations are required for validation of clinical stroke scores.
doi:10.4103/0976-3147.139966
PMCID: PMC4173228  PMID: 25288833
Besson score; Guy's hospital stroke score; Greek stroke score; Siriraj stroke score; stroke
2.  Fosphenytoin for seizure prevention in childhood coma in Africa: A randomized clinical trial☆☆☆★★★ 
Journal of Critical Care  2013;28(6):1086-1092.
Purpose
We conducted a double-blind trial to determine whether a single intramuscular injection of fosphenytoin prevents seizures and neurologic sequelae in children with acute coma.
Methods
We conducted this study at Kilifi District Hospital in coastal Kenya and Kondele Children's Hospital in western Kenya. We recruited children (age, 9 months to 13 years) with acute nontraumatic coma. We administered fosphenytoin (20 phenytoin equivalents/kg) or placebo and examined the prevalence and frequency of clinical seizures and occurrence of neurocognitive sequelae.
Results
We recruited 173 children (median age, 2.6 [interquartile range, 1.7-3.7] years) into the study; 110 had cerebral malaria, 8 had bacterial meningitis, and 55 had encephalopathies of unknown etiology. Eighty-five children received fosphenytoin and 88 received placebo. Thirty-three (38%) children who received fosphenytoin had at least 1 seizure compared with 32 (36%) who received placebo (P = .733). Eighteen (21%) and 15 (17%) children died in the fosphenytoin and placebo arms, respectively (P = .489). At 3 months after discharge, 6 (10%) children in the fosphenytoin arm had neurologic sequelae compared with 6 (10%) in the placebo arm (P = .952).
Conclusion
A single intramuscular injection of fosphenytoin (20 phenytoin equivalents/kg) does not prevent seizures or neurologic deficits in childhood acute nontraumatic coma.
doi:10.1016/j.jcrc.2013.09.001
PMCID: PMC3835934  PMID: 24135012
Coma; Child; Seizure; Prophylaxis; Anticonvulsants
3.  Value of Plasmodium falciparum Histidine-Rich Protein 2 Level and Malaria Retinopathy in Distinguishing Cerebral Malaria From Other Acute Encephalopathies in Kenyan Children 
The Journal of Infectious Diseases  2013;209(4):600-609.
Background. The diagnosis of cerebral malaria is problematic in malaria-endemic areas because encephalopathy in patients with parasitemia may have another cause. Abnormal retinal findings are thought to increase the specificity of the diagnosis, and the level of histidine-rich protein 2 (HRP2) may reflect the parasite biomass.
Methods. We examined the retina and measured plasma HRP2 levels in children with acute nontraumatic encephalopathy in Kenya. Logistic regression, with HRP2 level as an independent variable and World Health Organization–defined cerebral malaria and/or retinopathy as the outcome, was used to calculate malaria-attributable fractions (MAFs) and retinopathy-attributable fractions (RAFs).
Results. Of 270 children, 140 (52%) had peripheral parasitemia, 80 (30%) had malaria retinopathy, and 164 (61%) had an HRP2 level of >0 U/mL. During 2006–2011, the incidence of HRP2 positivity among admitted children declined by 49 cases per 100 000 per year (a 78% reduction). An HRP2 level of >0 U/mL had a MAF of 93% for cerebral malaria, with a MAF of 97% observed for HRP2 levels of ≥10 U/mL (the level of the best combined sensitivity and specificity). HRP2 levels of >0 U/mL had a RAF of 77% for features of retinopathy combined, with the highest RAFs for macular whitening (99%), peripheral whitening (98%), and hemorrhages (90%).
Conclusion. HRP2 has a high attributable fraction for features of malarial retinopathy, supporting its use in the diagnosis of cerebral malaria. HRP2 thresholds improve the specificity of the definition.
doi:10.1093/infdis/jit500
PMCID: PMC3903374  PMID: 24041795
attributable fractions; cerebral malaria; children; histidine-rich protein-2; malaria retinopathy
4.  The tympanic membrane displacement analyser for monitoring intracranial pressure in children 
Child's Nervous System  2013;29(6):927-933.
Purpose
Raised intracranial pressure (ICP) is a potentially treatable cause of morbidity and mortality but tools for monitoring are invasive. We sought to investigate the utility of the tympanic membrane displacement (TMD) analyser for non-invasive measurement of ICP in children.
Methods
We made TMD observations on normal and acutely comatose children presenting to Kilifi District Hospital (KDH) at the rural coast of Kenya and on children on follow-up for idiopathic intracranial hypertension at Evelina Children’s Hospital (ECH), in London, UK.
Results
We recruited 63 patients (median age 3.3 (inter-quartile range (IQR) 2.0–4.3) years) at KDH and 14 children (median age 10 (IQR 5–11) years) at ECH. We observed significantly higher (more negative) TMD measurements in KDH children presenting with coma compared to normal children seen at the hospital’s outpatient department, in both semi-recumbent [mean −61.3 (95 % confidence interval (95 % CI) −93.5 to 29.1) nl versus mean −7.1 (95 % CI −54.0 to 68.3) nl, respectively; P = 0.03] and recumbent postures [mean −61.4 (95 % CI −93.4 to −29.3) nl, n = 59) versus mean −25.9 (95 % CI −71.4 to 123.2) nl, respectively; P = 0.03]. We also observed higher TMD measurements in ECH children with raised ICP measurements, as indicated by lumbar puncture manometry, compared to those with normal ICP, in both semi-recumbent [mean −259.3 (95 % CI −363.8 to −154.8) nl versus mean 26.7 (95 % CI −52.3 to 105.7) nl, respectively; P < 0.01] and recumbent postures [mean −137.5 (95 % CI −260.6 to −14.4) nl versus mean 96.6 (95 % CI 6.5 to 186.6) nl, respectively; P < 0.01].
Conclusion
The TMD analyser has a potential utility in monitoring ICP in a variety of clinical circumstances.
doi:10.1007/s00381-013-2036-5
PMCID: PMC3657347  PMID: 23361337
Intracranial pressure; Idiopathic intracranial hypertension; Coma; Child
5.  Changing trends in incidence and aetiology of childhood acute non-traumatic coma over a period of changing malaria transmission in rural coastal Kenya: a retrospective analysis 
BMJ Open  2012;2(2):e000475.
Objectives
Recent changes in malaria transmission have likely altered the aetiology and outcome of childhood coma in sub-Saharan Africa. The authors conducted this study to examine change in incidence, aetiology, clinical presentation, mortality and risk factors for death in childhood non-traumatic coma over a 6-year period.
Design
Retrospective analysis of prospectively collected data.
Setting
Secondary level health facility: Kilifi, Coast, Kenya.
Participants
Children aged 9 months to 13 years admitted with acute non-traumatic coma (Blantyre Coma Score =2) between January 2004 and December 2009 to Kilifi District Hospital, Kenya. Exclusion criteria: delayed development, epilepsy and sickle cell disease.
Results
During the study period, 665 children (median age 32 (IQR 20–46) months; 46% were girls) were admitted in coma. The incidence of childhood coma declined from 93/100 000 children in 2004 to 44/100 000 children in 2009. There was a 64% overall drop in annual malaria-positive coma admissions and a 272% overall increase in annual admissions with encephalopathies of undetermined cause over the study period. There was no change in case death of coma. Vomiting, breathing difficulties, bradycardia, profound coma (Blantyre Coma Score=0), bacteraemia and clinical signs of meningitis were associated with increased risk of death. Seizures within 24 h prior to admission, and malaria parasitaemia, were independently associated with survival, unchanging during the study period.
Conclusion
The decline in the incidence and number of admissions of childhood acute non-traumatic coma is due to decreased malaria transmission. The relative and absolute increase in admissions of encephalopathy of undetermined aetiology could represent aetiologies previously masked by malaria or new aetiologies.
Article summary
Article focus
This study examines change in incidence, aetiology, clinical presentation, mortality and risk factors for death in childhood acute non-traumatic coma over a 6-year period of documented change in malaria transmission in rural coastal Kenya.
Key messages
There is an overall decline in childhood coma presentation over the study period, with a significant drop in malaria-positive coma admissions.
There is relative and absolute increase in coma admissions of undetermined aetiology.
There is an urgent need to examine for the role of viruses, metabolic derangements, vascular pathologies and other conditions in the aetiology of childhood non-traumatic coma.
Strengths and limitations of this study
The study is based on prospectively collected data in a setting where recommended standard clinical care is consistent and for which the catchment area is well delineated.
A number of children with acute coma likely die before arrival in hospital, and a few others are seen in a smaller hospital, which refers most of their comatose patients to the hospital in the study. Thus, the incidence figures are minimum incidences, likely an underestimation of the actual incidence.
doi:10.1136/bmjopen-2011-000475
PMCID: PMC3323808  PMID: 22466156
6.  Iron Deficiency and Acute Seizures: Results from Children Living in Rural Kenya and a Meta-Analysis 
PLoS ONE  2010;5(11):e14001.
Background
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.
Methods
We recruited 133 children, aged 3–156 months, who presented to a district hospital on the Kenyan coast with acute seizures and frequency-matched these to children of similar ages but without seizures. We defined iron deficiency according to the presence of malarial infection and evidence of inflammation. In patients with malaria, we defined iron deficiency as plasma ferritin<30µg/ml if plasma C-reactive protein (CRP) was<50mg/ml or ferritin<273µg/ml if CRP≥50mg/ml, and in those without malaria, as ferritin<12µg/ml if CRP<10mg/ml or ferritin<30µg/ml if CRP≥10mg/ml. In addition, we performed a meta-analysis of case-control studies published in English between January 1966 and December 2009 and available through PUBMED that have examined the relationship between iron deficiency and febrile seizures in children.
Results
In our Kenyan case control study, cases and controls were similar, except more cases reported past seizures. Malaria was associated with two-thirds of all seizures. Eighty one (30.5%) children had iron deficiency. Iron deficiency was neither associated with an increased risk of acute seizures (45/133[33.8%] cases were iron deficient compared to 36/133[27.1%] controls, p = 0.230) nor status epilepticus and it did not affect seizure semiology. Similar results were obtained when children with malaria, known to cause acute symptomatic seizures in addition to febrile seizures were excluded. However, in a meta-analysis that combined all eight case-control studies that have examined the association between iron deficiency and acute/febrile seizures to-date, iron deficiency, described in 310/1,018(30.5%) cases and in 230/1,049(21.9%) controls, was associated with a significantly increased risk of seizures, weighted OR 1.79(95%CI 1.03–3.09).
Conclusions
Iron deficiency is not associated with an increased risk of all acute seizures in children but of febrile seizures. Further studies should examine mechanisms involved and the implications for public health.
doi:10.1371/journal.pone.0014001
PMCID: PMC2982825  PMID: 21103365
7.  The role for osmotic agents in children with acute encephalopathies: a systematic review 
BMC Pediatrics  2010;10:23.
Background
Raised intracranial pressure (ICP) is known to complicate both traumatic and non-traumatic encephalopathies. It impairs cerebral perfusion and may cause death due to global ischaemia and intracranial herniation. Osmotic agents are widely used to control ICP. In children, guidelines for their use are mainly guided by adult studies. We conducted this review to determine the current evidence of the effectiveness of osmotic agents and their effect on resolution of coma and outcome in children with acute encephalopathy.
Methods
We searched several databases for published and unpublished studies in English and French languages, between January 1966 and March 2009. We considered studies on the use of osmotic agents in children aged between 0 and 16 years with acute encephalopathies. We examined reduction in intracranial pressure, time to resolution of coma, and occurrence of neurological sequelae and death.
Results
We identified four randomized controlled trials, three prospective studies, two retrospective studies and one case report. Hypertonic saline (HS) achieved greater reduction in intracranial pressure (ICP) compared to mannitol and other fluids; normal saline or ringer's lactate. This effect was sustained for longer when it was given as continuous infusion. Boluses of glycerol and mannitol achieved transient reduction in ICP. Oral glycerol was associated with lower mortality and neurological sequelae when compared to placebo in children with acute bacterial meningitis. HS was associated with lower mortality when compared to mannitol in children with non-traumatic encephalopathies.
Conclusion
HS appears to achieve a greater reduction in ICP than other osmotic agents. Oral glycerol seems to improve outcome among children with acute bacterial meningitis. A sustained reduction in ICP is desirable and could be achieved by modifying the modes and rates of administration of these osmotic agents, but these factors need further investigation.
doi:10.1186/1471-2431-10-23
PMCID: PMC2859077  PMID: 20398408
8.  HIV, Malnutrition and Invasive Bacterial Infection among Children with Severe Malaria 
Background
HIV infection, malnutrition and invasive bacterial infections (IBI) are reported among children with severe malaria. However, it is unclear whether their co-occurrence with falciparum parasitization and severe disease is by chance, or by association among children in malaria endemic areas.
Methods
We examined 3,068 consecutive paediatric admissions to a Kenyan district hospital with clinical features of severe malaria, and 592 community controls. We performed multivariable regression analysis with each case weighted for their probability of being due to falciparum malaria using estimates of the fraction of severe disease attributable to malaria at different parasite densities derived from cross sectional parasitological surveys from well children in the same community.
Results
HIV infection was present in 133/1071 (12%, 95%CI 11 to 15%) consecutive parasitemic admissions. Parasite densities were higher in HIV infected children. The odds of admission associated with HIV infection for admission with true severe falciparum malaria were 9.6 (95%CI 4.9 to 19), however this effect was restricted to children age ≥1 year. Malnutrition was present in 507/2,048 (25%, 95%CI 23 to 27%) consecutive parasitemic admissions. The odds associated with malnutrition for admission with true severe falciparum malaria were 4.0 (95%CI 2.9 to 5.5). IBI was detected in 127/2,048 (6.2%, 95%CI 5.2 to 7.3%) of consecutive parasitemic admissions. All three comorbidities were associated with increased case fatality.
Conclusions
HIV, malnutrition and IBI are biologically associated with severe disease due to falciparum malaria rather than being simply alternative diagnoses in co-incidentally parasitized children in an endemic area.
doi:10.1086/600299
PMCID: PMC2853703  PMID: 19548833
Malaria; HIV; Malnutrition; Meningitis; Bacteremia; Comorbidity
9.  Neonatal seizures in a rural Kenyan District Hospital: aetiology, Incidence and outcome of hospitalization 
BMC Medicine  2010;8:16.
Background
Acute seizures are common among children admitted to hospitals in resource poor countries. However, there is little data on the burden, causes and outcome of neonatal seizures in sub-Saharan Africa. We determined the minimum incidence, aetiology and immediate outcome of seizures among neonates admitted to a rural district hospital in Kenya.
Methods
From 1st January 2003 to 31st December 2007, we assessed for seizures all neonates (age 0-28 days) admitted to the Kilifi District Hospital, who were resident in a defined, regularly enumerated study area. The population denominator, the number of live births in the community on 1 July 2005 (the study midpoint) was modelled from the census data.
Results
Seizures were reported in 142/1572 (9.0%) of neonatal admissions. The incidence was 39.5 [95% confidence interval (CI) 26.4-56.7] per 1000 live-births and incidence increased with birth weight. The main diagnoses in neonates with seizures were sepsis in 85 (60%), neonatal encephalopathy in 30 (21%) and meningitis in 21 (15%), but only neonatal encephalopathy and bacterial meningitis were independently associated with seizures. Neonates with seizures had a longer hospitalization [median period 7 days - interquartile range (IQR) 4 to10] -compared to 5 days [IQR 3 to 8] for those without seizures, P = 0.02). Overall, there was no difference in inpatient case fatality between neonates with and without seizures but, when this outcome was stratified by birth weight, it was significantly higher in neonates ≥ 2.5 kg compared to low birth weight neonates [odds ratio 1.59 (95%CI 1.02 to 2.46), P = 0.037]. Up to 13% of the surviving newborn with seizures had neurological abnormalities at discharge.
Conclusion
There is a high incidence of neonatal seizures in this area of Kenya and the most important causes are neonatal encephalopathy and meningitis. The high incidence of neonatal seizures may be a reflection of the quality of the perinatal and postnatal care available to the neonates.
doi:10.1186/1741-7015-8-16
PMCID: PMC2846860  PMID: 20236524
10.  OVER-DIAGNOSIS AND CO-MORBIDITY OF SEVERE MALARIA IN AFRICAN CHILDREN: A GUIDE FOR CLINICIANS 
Severe malaria is clinically similar other severe febrile illnesses. However, in endemic areas, parasitological confirmation of parasitemia is often unavailable or unreliable. False positive malaria microscopy is common. The most important consequence of treating only for malaria when no parasitemia exists is failure to address other life threatening conditions. Invasive bacterial infections are detected in up to a third of children with clinical features of severe malaria but a negative slide. Even among genuinely parasitized children, severe illness is not always due to malaria in endemic areas. We believe that routine use of parenteral antibiotics among children with a positive malaria slide and life-threatening disease is warranted because invasive bacterial infections are likely to be under-ascertained and are associated with increased mortality. Published data on co-morbidity with HIV infection and malnutrition are reviewed. A structured approach to assessment and care is essential, and is largely independent of underlying etiology.
PMCID: PMC2669774  PMID: 18165469
11.  Haptoglobin HP2-2 genotype, α-thalassaemia and acute seizures in children living in a malaria-endemic area 
Epilepsy Research  2008;81(2-3):114-118.
Summary
Polymorphisms of the haptoglobin (HP) gene and deletions in α-globin gene (α-thalassaemia) are common in malaria-endemic Africa. The same region also has high incidence rates for childhood acute seizures. The haptoglobin HP2-2 genotype has been associated with idiopathic generalized epilepsies and altered iron metabolism in children with α-thalassaemia can potentially interfere with neurotransmission and increase the risk of seizures. We investigated the hypothesis that the HP2-2 genotype and the common African α-globin gene deletions are associated with the increased risk of seizures. 288 children aged 3–156 months admitted with acute seizures to Kilifi District Hospital (Kenya), were matched for ethnicity to an equal number of community controls. The proportion of cases (72/288 [25.0%]) and controls (80/288 [27.8%]) with HP2-2 genotype was similar, p = 0.499. The allele frequency of HP2 gene in cases (49.3%) and controls (48.6%) was also similar, p = 0.814. Similarly, we found no significant difference between the proportion of cases (177/267 [66.3%]) and controls (186/267 [69.7%]) with deletions in α-globin gene (p = 0.403). Among cases, HP2-2 polymorphism and deletions in α-globin gene were neither associated with changes in the type, number or duration of seizures nor did they affect outcome. We conclude that the HP2-2 polymorphism and deletions in α-globin gene are not risk factors for acute seizures in children. Future studies should examine other susceptibility genes.
doi:10.1016/j.eplepsyres.2008.04.021
PMCID: PMC2670977  PMID: 18554871
Haptoglobin genotypes; α-Thalassaemia; Acute seizures and children
12.  The incidence, aetiology and outcome of acute seizures in children admitted to a rural Kenyan district hospital 
BMC Pediatrics  2008;8:5.
Background
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.
Methods
We recruited all children with and without seizures, aged 0–13 years and admitted to Kilifi District hospital over 2 years from 1st December 2004 to 30th November 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 30th November 2005 (study midpoint), was modelled from a census data.
Results
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.
Conclusion
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.
doi:10.1186/1471-2431-8-5
PMCID: PMC2270816  PMID: 18261215
15.  Volume Expansion with Albumin Compared to Gelofusine in Children with Severe Malaria: Results of a Controlled Trial  
PLoS Clinical Trials  2006;1(5):e21.
Objectives:
Previous studies have shown that in children with severe malaria, resuscitation with albumin infusion results in a lower mortality than resuscitation with saline infusion. Whether the apparent benefit of albumin is due solely to its colloidal properties, and thus might also be achieved with other synthetic colloids, or due to the many other unique physiological properties of albumin is unknown. As albumin is costly and not readily available in Africa, examination of more affordable colloids is warranted. In order to inform the design of definitive phase III trials we compared volume expansion with Gelofusine (succinylated modified fluid gelatin 4% intravenous infusion) with albumin.
Design:
This study was a phase II safety and efficacy study.
Setting:
The study was conducted at Kilifi District Hospital, Kenya.
Participants:
The participants were children admitted with severe falciparum malaria (impaired consciousness or deep breathing), metabolic acidosis (base deficit > 8 mmol/l), and clinical features of shock.
Interventions:
The interventions were volume resuscitation with either 4.5% human albumin solution or Gelofusine.
Outcome Measures:
Primary endpoints were the resolution of shock and acidosis; secondary endpoints were in-hospital mortality and adverse events including neurological sequelae.
Results:
A total of 88 children were enrolled: 44 received Gelofusine and 44 received albumin. There was no significant difference in the resolution of shock or acidosis between the groups. Whilst no participant developed pulmonary oedema or fluid overload, fatal neurological events were more common in the group receiving gelatin-based intervention fluids. Mortality was lower in patients receiving albumin (1/44; 2.3%) than in those treated with Gelofusine (7/44; 16%) by intention to treat (Fisher's exact test, p = 0.06), or 1/40 (2.5%) and 4/40 (10%), respectively, for those treated per protocol (p = 0.36). Meta-analysis of published trials to provide a summary estimate of the effect of albumin on mortality showed a pooled relative risk of death with albumin administration of 0.19 (95% confidence interval 0.06–0.59; p = 0.004 compared to other fluid boluses).
Conclusions:
In children with severe malaria, we have shown a consistent survival benefit of receiving albumin infusion compared to other resuscitation fluids, despite comparable effects on the resolution of acidosis and shock. The lack of similar mortality benefit from Gelofusine suggests that the mechanism may involve a specific neuroprotective effect of albumin, rather than solely the effect of the administered colloid. Further exploration of the benefits of albumin is warranted in larger clinical trials.
Editorial Commentary
Background: In Africa, children admitted to hospital with severe malaria are at high risk of death even though effective malaria treatment is available. Death typically occurs during a narrow time window after admission and before antimalarial treatments can start working. Acidosis (excessive acidity of the blood) is thought to predict death, but it is not clear how acidosis arises. One possibility is that hypovolemia (lowered blood fluid volume) is important, which would normally require urgent resuscitation with fluids. However, there is little evidence on what type of fluid should be given. In the trial reported here, carried out in Kenya's Kilifi District Hospital between 2004 and 2006, 88 children admitted with severe malaria were assigned to receive either albumin solution (a colloid solution made from blood protein) or Gelofusine (a synthetic colloid). The primary outcomes that the researchers were interested in were correction of shock and acidosis in the blood after 8 h. However, the researchers also looked at death rate in hospital and adverse events after treatment.
What this trial shows: The investigators found no significant differences in the primary outcomes (correction of shock and acidosis in the blood 8 h after fluids were started) between children given Gelofusine and those given albumin. However, they did see a difference in death rates between children given Gelofusine and those given albumin. Death rates in hospital were lower in the group given albumin, and this was statistically significant. The researchers then combined the data on death rates from this trial with data from two other trials with an albumin arm. This combined analysis also supported the suggestion that death rates with albumin were lower than with other fluids, either Gelofusine or salt solution.
Strengths and limitations: There is currently very little evidence from trials to guide the initial management of fluids in children with severe malaria. The results from this trial indicate that further research is a priority. However, the actual findings from this trial must be tested in larger trials that recruit enough children to establish reliably whether there is a difference in death rate between albumin treatment and treatment with other fluids. This trial was not originally planned to find a clinically relevant difference in death rate, and therefore does not definitively answer that question. Further trials would also need to use a random method to assign participants to the different treatments, rather than alternate blocks (as in this trial). A random method ensures greater comparability of the two groups in the trial, and reduces the chance of selection bias (where assignment of patients to different treatments can be distorted during the enrollment process).
Contribution to the evidence: This study adds data suggesting that fluid resuscitation with albumin solution, as compared to Gelofusine, may reduce the chance of death in children with severe malaria. However, this finding is not definitive and would need to be examined in further carefully controlled trials. If the finding is supported by further research, then a solution to the problems of high cost and limited availability of albumin will need to be found.
doi:10.1371/journal.pctr.0010021
PMCID: PMC1569382  PMID: 16998584
16.  Continuous EEG monitoring in Kenyan children with non-traumatic coma 
Archives of Disease in Childhood  2012;97(4):343-349.
Background
The aim of this study was to describe the EEG and clinical profile of seizures in children with non-traumatic coma, compare seizure detection by clinical observations with that by continuous EEG, and relate EEG features to outcome.
Methods
This prospective observational study was conducted at the paediatric high dependency unit of Kilifi District Hospital, Kenya. Children aged 9 months to 13 years presenting with acute coma were monitored by EEG for 72 h or until they regained consciousness or died. Poor outcome was defined as death or gross motor deficits at discharge.
Results
82 children (median age 2.8 (IQR 2.0–3.9) years) were recruited. An initial medium EEG amplitude (100–300 mV) was associated with less risk of poor outcome compared to low amplitude (≤100 mV) (OR 0.2, 95% CI 0.1 to 0.7; p<0.01). 363 seizures in 28 (34%) children were observed: 240 (66%) were electrographic and 112 (31%) electroclinical. In 16 (20%) children, electrographic seizures were the only seizure types detected. The majority (63%) of electroclinical seizures had focal clinical features but appeared as generalised (79%) or focal with secondary generalisation (14%) on EEG. Occurrence of any seizure or status epilepticus during monitoring was associated with poor outcome (OR 3.2, 95% CI 1.2 to 8.7; p=0.02 and OR 4.5, 95% CI 1.3 to 15.3; p<0.01, respectively).
Conclusion
Initial EEG background amplitude is prognostic in paediatric non-traumatic coma. Clinical observations do not detect two out of three seizures. Seizures and status epilepticus after admission are associated with poor outcome.
doi:10.1136/archdischild-2011-300935
PMCID: PMC3329232  PMID: 22328741

Results 1-16 (16)