Samson Gwer

Value of Plasmodium falciparum histidine-rich protein 2 level and malaria retinopathy in distinguishing cerebral malaria from other acute encephalopathies in Kenyan children.

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.

Research priorities in the management of severe Plasmodium falciparum malaria in children

Abstract Severe malaria is a common reason for admission to paediatric wards in hospitals across sub-Saharan Africa. Despite over 100 years of research, mortality remains high. Deaths are associated with severe metabolic acidosis, shock, severe anaemia, hypoglycaemia, impaired consciousness, raised intracranial pressure, and status epilepticus. Most inpatient deaths occur within 24 h of admission to hospital, before the beneficial effects of treatment with antimalarial drugs are achieved. This review covers the priority areas for research in the care of children with severe malaria, addressing each of the main risk factors associated with death, in a bid to reduce the inpatient mortality.

Childhood acute non-traumatic coma: aetiology and challenges in management in resource-poor countries of Africa and Asia.

Abstract 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.

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, Guys 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 Guys 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.

Fosphenytoin for seizure prevention in childhood coma in Africa: A randomized clinical trial

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 Childrens 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.

Early management of traumatic brain injury in a Tertiary hospital in Central Kenya: A clinical audit

Background: Traumatic brain injury (TBI) is a major cause of death and disability worldwide and is mostly attributed to road traffic accidents in resource-poor areas. However, access to neurosurgical care is poor in these settings and patients in need of neurosurgical procedures are often managed by general practitioners or surgeons. Materials and Methods: A retrospective clinical audit of the initial management of patients with TBI in Thika Level 5 Hospital (TL5H), a Tertiary Hospital in Central Kenya. Seventeen audit criteria divided into five clinical domains were identified and patient case notes reviewed for compliance with each criterion. Data were analyzed separately for those below 13 years owing to differences in response to brain trauma in those below this age. Results: Overall, there was poor compliance with audit criteria in both groups. Among those below 13 years of age, only 3 out of 17 criteria achieved compliance and 4 out of 17 criteria achieved compliance for those above 13 years of age. Assessment for the need for a cervical radiograph (7.1% and 8.8% compliance) and administration of oxygen (21.4% and 20.6% compliance) had the worst performance in both groups. Conclusion: Poor compliance to audit criteria indicates the low quality of care for patients with TBI in TL5H. Quality improvement strategies with follow-up audits are needed to improve care. There is a need to develop and enforce evidence-based protocols and guidelines for use in the management of patients with TBI in sub-Saharan Africa.

Unexpected Relationship Between Tympanometry and Mortality in Children With Nontraumatic Coma

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.

Antimalarial drugs and the prevalence of mental and neurological manifestations: A systematic review and meta-analysis

Background: Antimalarial drugs affect the central nervous system, but it is difficult to differentiate the effect of these drugs from that of the malaria illness. We conducted a systematic review to determine the association between anti-malarial drugs and mental and neurological impairment in humans. Methods: We systematically searched online databases, including Medline/PubMed, PsychoInfo, and Embase, for articles published up to 14th July 2016. Pooled prevalence, heterogeneity and factors associated with prevalence of mental and neurological manifestations were determined using meta-analytic techniques. Results: Of the 2,349 records identified in the initial search, 51 human studies met the eligibility criteria. The median pooled prevalence range of mental and neurological manifestations associated with antimalarial drugs ranged from 0.7% (dapsone) to 48.3% (minocycline) across all studies, while it ranged from 0.6% (pyrimethamine) to 42.7% (amodiaquine) during treatment of acute malaria, and 0.7% (primaquine/dapsone) to 55.0% (sulfadoxine) during prophylaxis. Pooled prevalence of mental and neurological manifestations across all studies was associated with an increased number of antimalarial drugs (prevalence ratio= 5.51 (95%CI, 1.05-29.04); P=0.045) in a meta-regression analysis. Headaches (15%) and dizziness (14%) were the most common mental and neurological manifestations across all studies. Of individual antimalarial drugs still on the market, mental and neurological manifestations were most common with the use of sulphadoxine (55%) for prophylaxis studies and amodiaquine (42.7%) for acute malaria studies. Mefloquine affected more domains of mental and neurological manifestations than any other antimalarial drug. Conclusions: Antimalarial drugs, particularly those used for prophylaxis, may be associated with mental and neurological manifestations, and the number of antimalarial drugs taken determines the association. Mental and neurological manifestations should be assessed following the use of antimalarial drugs.

Abnormal intra-aural pressure waves associated with death in African children with acute nontraumatic coma.

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.