RP-Department of Medical Physiology

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Abnormal Intra-aural Pressure Waves Associated with Death in African Children with acute Nontraumatic Coma.
(Nature Publishing Group, 2015) Gwer, S.; Kazungu, M.; Chengo, E.; Ohuma, E. O.; Idro, R.; Birch, T.; Marchbanks, R.; Kirkham, F. J.; Newton, C. R.
BACKGROUND: We explored the relationship between tympanic membrane displacement (TMD) measurements, a tool to monitor intracranial pressure noninvasively, and clinical features and death in children with acute coma in Kilifi, Kenya. METHODS: Between November 2007 and September 2009, we made serial TMD measurements and clinical observations on children with acute coma (Blantyre coma score (BCS) ≤ 2) on the pediatric high dependency unit of Kilifi District Hospital, and on well children presenting to the hospital's outpatient department for routine follow-up. We examined middle ear function using tympanometry and measured cardiac pulse (CPA) and respiratory pulse pressure amplitudes (RPA) using the TMD analyzer. RESULTS: We recruited 75 children (32 (43%) females; median age 3.3 (IQR: 2.0, 4.3) years). Twenty-one (28%) children died. Higher TMD measurements predicted death. Adjusting for diagnosis, every 50 nl rise in both semirecumbent and recumbent CPA was associated with increased odds of death associated with intracranial herniation (OR: 1.61, 95% confidence interval (CI): 1.07, 2.41; P = 0.02 and OR: 1.35, 95% CI: 1.10, 1.66; P ≤ 0.01 respectively). CONCLUSION: Raised TMD pulse pressure measurements are associated with death and may be useful in detecting and monitoring risk of intracranial herniation and intracranial pressure in childhood coma.
Childhood acute non-traumatic coma: aetiology and challenges in management in resource-poor countries of Africa and Asia.
(Maney Publishing, 2013-08) Gwer, S.; Chacha, C.; Newton, C.R.; Idro, R.
OBJECTIVE: This review examines the best available evidence on the aetiology of childhood acute non-traumatic coma in resource-poor countries (RPCs), discusses the challenges associated with management, and explores strategies to address them. METHODS: Publications in English and French which reported on studies on the aetiology of childhood non-traumatic coma in RPCs are reviewed. Primarily, the MEDLINE database was searched using the keywords coma, unconsciousness, causality, aetiology, child, malaria cerebral, meningitis, encephalitis, Africa, Asia, and developing countries. RESULTS: 14 records were identified for inclusion in the review. Cerebral malaria (CM) was the commonest cause of childhood coma in most of the studies conducted in Africa. Acute bacterial meningitis (ABM) was the second most common known cause of coma in seven of the African studies. Of the studies in Asia, encephalitides were the commonest cause of coma in two studies in India, and ABM was the commonest cause of coma in Pakistan. Streptococcus pneumoniae was the most commonly isolated organism in ABM. Japanese encephalitis, dengue fever and enteroviruses were the viral agents most commonly isolated. CONCLUSION: Accurate diagnosis of the aetiology of childhood coma in RPCs is complicated by overlap in clinical presentation, limited diagnostic resources, disease endemicity and co-morbidity. For improved outcomes, studies are needed to further elucidate the aetiology of childhood coma in RPCs, explore simple and practical diagnostic tools, and investigate the most appropriate specific and supportive interventions to manage and prevent infectious encephalopathies.
Clinical stroke scores for distinguishing stroke subtypes: a systematic review of diagnostic test accuracy
(2013-04) Gwer, S.; Mwita, C.; Kajia, D.; Newton, C.R.
Background Stroke is a major cause of morbidity and mortality especially in low and middle income countries. Computerized tomography is used to distinguish between ischemic and hemorrhagic subtypes, but it is expensive and unavailable in some low and middle income countries. Clinical stroke scores are proposed to differentiate between ischemic and hemorrhagic stroke but their reliability is unknown. Objective To synthesize the best available research evidence on the accuracy of clinical scores in distinguishing ischemic and hemorrhagic stroke in patients with acute stroke. Inclusion Criteria Participants Patients admitted to hospital with acute stroke according to the World Health Organization criteria, regardless of age, sex or ethnicity. Intervention This review considered studies that evaluated the Siriraj, Guy’s Hospital, Besson and Greek stroke scores compared to computerized tomography as the reference standard. Outcomes The sensitivity and specificity of the clinical stroke scores compared to computerized tomography results in distinguishing between stroke subtypes. Types of Studies This review considered studies of diagnostic test accuracy in which the index test(s) and reference standard were interpreted independently of one another on the same group of participants. Search Strategy We searched online databases for published and unpublished studies written in English and identified articles using predefined criteria. Methodological Quality Papers selected for retrieval were assessed by four independent reviewers for methodological validity prior to inclusion in the review using the QUality Assessment of Diagnostic Accuracy Studies tool. Data Extraction A modified Joanna Briggs Institute data extraction form was used to collect details from included studies. Data Synthesis A bivariate mixed effects binomial regression model was used to statistically pool data in meta-analysis. A narrative synthesis was undertaken where statistical pooling was not feasible. Results For studies from low and middle income countries, overall 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. For the Greek stroke score, sensitivity and specificity ranged from 0.39 to 0.64 and 0.63 to 0.88 for ischemic stroke and 0.11 to 0.44 and 0.63 to 0.96 for hemorrhagic stroke. Discussion Clinical stroke scores were developed for use in settings where computerized tomography scan is unavailable to differentiate between stroke subtypes but they minimally alter the post-test probability of disease and thus are not sufficiently accurate to replace neuro-imaging in differentiating stroke subtypes. Conclusions Clinical stroke scores are not accurate enough for use in clinical or epidemiological settings. Use of computerized tomography is recommended for differentiating stroke subtypes.
Iron deficiency and acute seizures: results from children living in rural Kenya and a meta-analysis.
(Public Library of Science, 2010-11) Gwer, S.; Idro, R.; Williams, T. N.; Otieno, T.; Uyoga, S.; Fegan, G.; Kager, P. A.; Maitland, K.; Kirkham, F.; Neville, B. G.; Newton, C. R.
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<30 µg/ml if plasma C-reactive protein (CRP) was<50 mg/ml or ferritin<273 µg/ml if CRP≥50 mg/ml, and in those without malaria, as ferritin<12 µg/ml if CRP<10 mg/ml or ferritin<30 µg/ml if CRP≥10 mg/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.
Neonatal seizures in a rural Kenyan District Hospital: aetiology, incidence and outcome of hospitalization
(BioMed Central, 2010-03) Gwer, S.; Mwaniki, M.; Mturi, N.; Bauni, E.; Newton, C. R.; Berkley, J.; Idro, R.
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 >or= 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.
Over-diagnosis and co-morbidity of severe malaria in African children: a guide for clinicians.
(The American Journal of Tropical Medicine and Hygiene, 2007-12) Gwer, S.; Newton, C.R.; Berkley, J.A.
Severe malaria is clinically similar to 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 one third of children with clinical features of severe malaria but a slide with results negative for malaria. 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 slide that indicates malaria 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.
Unexpected relationship between tympanometry and mortality in children with nontraumatic coma.
(American Academy of Pediatrics ., 2013-09) Gwer, S.; Chengo, E.; Newton, C.R.; Kirkham, F.J.
OBJECTIVE: We sought to further examine the relationship between tympanometry and mortality after noting an unexpected association on assessment of baseline data of a study whose primary aim was to investigate the utility of noninvasive tympanic membrane displacement measurement for monitoring intracranial pressure in childhood coma. METHODS: We recruited children who presented with acute nontraumatic coma to the high-dependency unit of Kilifi District Hospital on the rural coast of Kenya. We excluded children with sickle cell disease, epilepsy, and neurodevelopmental delay. We performed tympanometry on the right ear before tympanic membrane displacement analyzer measurements. All children were managed according to standard World Health Organization guidelines. RESULTS: We recruited 72 children with a median age of 3.2 years (interquartile range [IQR]: 2.0-4.3 years); 31 (43%) were female. Thirty-eight (53%) had cerebral malaria, 8 (11%) acute bacterial meningitis, 4 (6%) sepsis, and 22 (30%) encephalopathy of unknown etiology. Twenty (28%) children died. Tympanometry was normal in 25 (35%) children. Adjusting for diagnosis and clinical features of increased intracranial pressure, both associated with death on univariable analysis, children with abnormal tympanometry had greater odds of dying than did those with normal tympanometry (adjusted odds ratio: 17.0; 95% confidence interval: 1.9-152.4; P = .01). Children who died had a lower compliance (0.29 mL; IQR: 0.09-0.33 mL) compared with those who survived (0.48 mL; IQR: 0.29-0.70 mL) (P < .01). CONCLUSIONS: Abnormal tympanometry appears to be significantly associated with death in children with acute nontraumatic coma. This finding needs to be explored further through a prospective study that incorporates imaging and intensive physiologic monitoring. KEYWORDS: Child, encephalopathy, infectious disease, outcome, tympanometry
Value of Plasmodium falciparum Histidine-Rich Protein 2 Level and Malaria Retinopathy in Distinguishing Cerebral Malaria From Other Acute Encephalopathies in Kenyan Children.
(Journal of Infectious Diseases Advance Access published, 2013-10-09) Gwer, S.; Kariuki, S.M.; Gitau, E.; Karanja, H.K.; Chengo, E.; Urban, B.C.; Newton, C.R.
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 We examined the retina and measured plasma HRP2 levels biomass. Methods. 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 Of 270 children, 140 retinopathy-attributable fractions (RAFs).Results. (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 HRP2 has a high attributable fraction for features of (90%).Conclusion. malarial retinopathy, supporting its use in the diagnosis of cerebral malaria. HRP2 thresholds improve the specificity of the definition. KEYWORDS: attributable fractions, cerebral malaria, children, histidine-rich protein-2, malaria retinopathy

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