RESUMO
This is the second report of the United Kingdom Primary Immunodeficiency (UKPID) registry. The registry will be a decade old in 2018 and, as of August 2017, had recruited 4758 patients encompassing 97% of immunology centres within the United Kingdom. This represents a doubling of recruitment into the registry since we reported on 2229 patients included in our first report of 2013. Minimum PID prevalence in the United Kingdom is currently 5·90/100 000 and an average incidence of PID between 1980 and 2000 of 7·6 cases per 100 000 UK live births. Data are presented on the frequency of diseases recorded, disease prevalence, diagnostic delay and treatment modality, including haematopoietic stem cell transplantation (HSCT) and gene therapy. The registry provides valuable information to clinicians, researchers, service commissioners and industry alike on PID within the United Kingdom, which may not otherwise be available without the existence of a well-established registry.
Assuntos
Monitoramento Epidemiológico , Síndromes de Imunodeficiência/epidemiologia , Sistema de Registros/estatística & dados numéricos , Feminino , Humanos , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/terapia , Masculino , Reino Unido/epidemiologiaRESUMO
Autoimmune lymphoproliferative syndrome (ALPS) is mainly caused by defects in the CD95 pathway. Raised CD3+TCRαß+CD4-CD8- double negative T cells and impaired T cell apoptosis are hallmarks of the disease. In contrast, the B cell compartment has been less well studied. We found an altered distribution of B cell subsets with raised transitional B cells and reduced marginal zone B cells, switched memory B cells and plasma blasts in most of 22 analyzed ALPS patients. Moreover, 5 out of 66 ALPS patients presented with low IgG and susceptibility to infection revealing a significant overlap between ALPS and common variable immunodeficiency (CVID). In patients presenting with lymphoproliferation, cytopenia, hypogammaglobulinemia and impaired B cell differentiation, serum biomarkers were helpful in addition to apoptosis tests for the identification of ALPS patients. Our observations may indicate a role for apoptosis defects in some diseases currently classified as CVID.
Assuntos
Síndrome Linfoproliferativa Autoimune/diagnóstico , Síndrome Linfoproliferativa Autoimune/imunologia , Linfócitos B/imunologia , Imunodeficiência de Variável Comum/diagnóstico , Imunodeficiência de Variável Comum/imunologia , Proteína Ligante Fas/sangue , Interleucina-10/sangue , Vitamina B 12/sangue , Adolescente , Adulto , Agamaglobulinemia/imunologia , Apoptose , Biomarcadores/sangue , Criança , Pré-Escolar , Diagnóstico Diferencial , Proteína Ligante Fas/imunologia , Citometria de Fluxo , Humanos , Imunoglobulina G/sangue , Interleucina-10/imunologia , Pessoa de Meia-Idade , Monócitos/imunologia , Fenótipo , Linfócitos T/imunologia , Vitamina B 12/imunologia , Receptor fas/sangue , Receptor fas/imunologiaRESUMO
This review focuses on the latest knowledge and understanding of febrile seizures and outlines the more important issues in the management of children who present with an apparent "febrile seizure". It is not the remit of this paper to discuss the detailed management of febrile seizures. Throughout this review, the words "partial" and "focal" will be used interchangeably and the term "febrile seizure" (FS) will be used, reflecting the proposed changes in the terminology of seizures and epilepsies.1
Assuntos
Convulsões Febris/fisiopatologia , Anticonvulsivantes/administração & dosagem , Doenças do Sistema Nervoso Central/etiologia , Doenças do Sistema Nervoso Central/fisiopatologia , Criança , Diazepam/administração & dosagem , Epilepsia do Lobo Temporal/etiologia , Epilepsia do Lobo Temporal/fisiopatologia , Humanos , Prognóstico , Recidiva , Fatores de Risco , Convulsões Febris/complicações , Convulsões Febris/diagnósticoRESUMO
Hyponatraemia is common in African children with severe malaria, but the cause is unknown. We measured plasma sodium (p[Na]) and arginine vasopressin concentrations (p[AVP]) in 30 consecutive children with severe malaria (19 had cerebral malaria), on admission, at 48 and 96 h after admission. Hyponatraemia (p[Na] < 130 mmol/l) occurred in 53 per cent of the children and was unrelated to peripheral parasite density, dehydration or abnormal renal function. The highest p[AVP] were seen in patients with cerebral malaria. Overall, p[AVP] declined 96 h after treatment. In children with hyponatraemia (cerebral and non-cerebral), p[AVP] levels were not suppressed and in 67 per cent of cases they were deemed inappropriate. Inappropriate AVP secretion is common in children with severe malaria and may influence fluid therapy after correction of initial dehydration.
Assuntos
Arginina Vasopressina/sangue , Hiponatremia/sangue , Malária Cerebral/sangue , Arginina Vasopressina/metabolismo , Pré-Escolar , Feminino , Humanos , Malária Cerebral/urina , MasculinoRESUMO
The district general hospital (DGH) is a common feature of health service provision in many developing countries. We have used linked demographic and clinical surveillance in a rural community located close to a DGH on the Kenyan coast to define the use and public health significance of essential clinical services provided by it. Of a birth cohort of over 4000 children followed for approximately 6 years, about a third were admitted to hospital at least once. Significantly more children admitted with major infectious diseases such as malaria and acute respiratory tract infections were readmitted with the same condition during the surveillance period than would have been expected by chance. Among surviving admissions, mortality post-discharge was significantly higher than in the cohort which had not been admitted within 3, 6 and 12 months. Most of the patients who died after discharge had been admitted with a diagnosis of gastroenteritis. Most children admitted to the DGH survive hospitalization and the remaining period of childhood. Despite no clinical trial evidence to support the claim, it seems reasonable to assume that in the absence of intensive clinical management provided by a DGH, a significant proportion of these children would not have survived. However, the DGH is able to define a group of at-risk children who re-present with severe complications of infectious disease, and of these several may have underlying conditions not amenable to DGH intervention and continue to have a poor prognosis. Both groups of children represent statistically significant subsets of a rural paediatric community and the future organization and co-ordination of DGH and primary care services need to work in unison to strengthen the service needs of children at risk.
Assuntos
Hospitalização , Malária/mortalidade , Criança , Seguimentos , Humanos , Readmissão do Paciente , RiscoRESUMO
The pathogenesis of cerebral malaria is poorly understood. One hypothesis is that activation of microglia and astrocytes in the brain might cause the cerebral symptoms by excitotoxic mechanisms. Cerebrospinal fluid was sampled in 97 Kenyan children with cerebral malaria, 85% within 48 hr of admission. When compared with an age-matched reference range, there were large increases in concentrations of the excitotoxin quinolinic acid (geometric mean ratio cerebral malaria/reference population [95% confidence limits] = 14.1 [9.8-20.4], P < 0.001) and total neopterin (10.9 [9.1-13.0], P < 0.001) and lesser increases in tetra-hydrobiopterin, di-hydrobiopterin, and 5-hydroxyindoleacetic acid. There was no change in tryptophan concentration. In contrast, nitrate plus nitrite concentrations were decreased (geometric mean ratio = 0.45 [0.35-0.59], P < 0.001). There was a graded increment in quinolinic acid concentration across outcome groups of increasing severity. The increased concentration of quinolinic acid suggests that excitotoxic mechanisms may contribute to the pathogenesis of cerebral malaria.
Assuntos
Encéfalo/parasitologia , Malária Cerebral/etiologia , Ácido Quinolínico/líquido cefalorraquidiano , Antimaláricos/uso terapêutico , Biopterinas/análogos & derivados , Biopterinas/líquido cefalorraquidiano , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Endotélio/parasitologia , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Lactente , Quênia , Malária Cerebral/líquido cefalorraquidiano , Malária Cerebral/tratamento farmacológico , Malária Cerebral/parasitologia , Microglia/parasitologia , Neopterina/líquido cefalorraquidiano , Nitratos/líquido cefalorraquidiano , Nitritos/líquido cefalorraquidiano , Triptofano/líquido cefalorraquidianoRESUMO
BACKGROUND: Seizures commonly complicate cerebral malaria and are associated with an increased risk of death and neurological sequelae. We undertook a randomised study to assess the efficacy of intramuscular phenobarbital in preventing seizures in childhood cerebral malaria. METHODS: Children with cerebral malaria admitted to one hospital in Kilifi, Kenya, were randomly assigned a single intramuscular dose of phenobarbital (20 mg/kg) or identical placebo. Clinical tolerance was assessed at the start of the trial, with particular reference to respiratory depression and hypotension. Seizures were timed and recorded, and treated in a standard way. Plasma phenobarbital concentrations were measured. Analyses were by intention to treat. FINDINGS: 440 children with cerebral malaria were admitted to the hospital; 100 were not recruited to the study. Of the remaining 340, 170 received phenobarbital and 170 placebo. The drug was adequately absorbed and well tolerated. Seizure frequency was significantly lower in the phenobarbital group than in the placebo group (18 [11%] vs 46 [27%] children had three or more seizures of any duration; odds ratio 0.32 [95% CI 0.18-0.58]) but mortality was doubled (30 [18%] vs 14 [8%] deaths; 2.39 [1.28-4.64]). The frequency of respiratory arrest was higher in the phenobarbital group than in the placebo group, and mortality was greatly increased in children who received phenobarbital plus three or more doses of diazepam (odds ratio 31.7 [1.2-814]). INTERPRETATION: In children with cerebral malaria, phenobarbital 20 mg/kg provides highly effective seizure prophylaxis but is associated with an unacceptable increase in mortality. Use of this dose cannot, therefore, be recommended.
PIP: This randomized, placebo-controlled study assesses whether a single intramuscular dose of phenobarbital (20 mg/kg) given on admission to Kenyan children with cerebral malaria could lower the frequency of seizures, which complicate cerebral malaria by increasing the risk of death and neurological sequelae. A total of 340 children with cerebral malaria were admitted to the hospital; 170 received phenobarbital and 170 received placebo. The drug was adequately absorbed and well tolerated. Findings revealed a significantly lower frequency of seizures in the phenobarbital group than in the placebo group (18 [11%] vs. 46 [27%] children had 3 or more seizures of any duration; odds ratio (OR), 0.32; 95% confidence interval (CI), 0.18-0.58). However, mortality was doubled (30 [18%] vs. 14 [8%] deaths; OR, 2.39; 95% CI, 1.28-4.64) in the phenobarbital group. In addition, the frequency of respiratory arrest was higher in the phenobarbital group than in the placebo group, and mortality was greatly increased in children who received phenobarbital plus 3 or more doses of diazepam. In conclusion, although the phenobarbital dose of 20 mg/kg given to children with cerebral malaria provides highly effective seizure prophylaxis, an unacceptable increase in mortality is noted; hence, use of this dosage is not recommended.
Assuntos
Anticonvulsivantes/uso terapêutico , Malária Cerebral/complicações , Fenobarbital/uso terapêutico , Plasmodium falciparum , Convulsões/etiologia , Convulsões/prevenção & controle , Adolescente , Animais , Anticonvulsivantes/sangue , Anticonvulsivantes/farmacocinética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Infusões Intravenosas , Injeções Intramusculares , Quênia , Malária Cerebral/mortalidade , Masculino , Fenobarbital/sangue , Fenobarbital/farmacocinéticaRESUMO
Of 295 children with cerebral malaria, 117 (40%) had an abnormal respiratory pattern; 15 children exhibited more than one pattern during their clinical course. Four distinct patterns were seen. (i) Deep breathing (80 children); this was associated with severe metabolic acidosis, and resolved following treatment with intravenous fluids and/or blood. (ii) Hypoventilation with nystagmus and salivation (18 children); simultaneous electroencephalographic recording revealed continuous electrical seizure activity, demonstrating that these children were in subtle status epilepticus; anticonvulsant treatment resulted in return to normal of blood gases and recovery of consciousness. (iii) Hyperventilation with extensor posturing (20 children), which was associated with varying degrees of intracranial hypertension. (iv) Periodic respiration (14 children); all had clinical features suggestive of transtentorial herniation, and died following a respiratory arrest. Abnormal respiratory patterns can alert the clinician to complications of cerebral malaria that require treatment. Recognition of these patterns and rapid initiation of appropriate supportive therapy may help to reduce the high mortality rate of this disease.
Assuntos
Hiperventilação/etiologia , Malária Cerebral/complicações , Insuficiência Respiratória/etiologia , Animais , Pré-Escolar , Humanos , Hiperventilação/fisiopatologia , Lactente , Quênia , Malária Cerebral/fisiopatologia , Plasmodium falciparum/isolamento & purificação , Insuficiência Respiratória/fisiopatologiaRESUMO
By US standards, about half of African children are malnourished, although most appear clinically normal. It is possible that precursor supply for gluconeogenesis is limited to a greater extent in these seemingly malnourished African children than in healthy children, consequently limiting glucose production. Since in malaria peripheral glucose utilization is increased, precursor supply could play an even more critical role in maintaining glucose production in African children suffering from falciparum malaria. We studied the effect of alanine infusion (1.5 mg/kg/min) on glucose production (measured by infusion of [6,6-2H2]glucose) and plasma glucose concentration in 10 consecutive children with acute, uncomplicated falciparum malaria. By US standards, six children were below the 10th percentile of weight for height and seven were below the 10th percentile of height for age. Plasma concentrations of alanine increased during alanine infusion from 153 +/- 21 to 468 +/- 39 mumol/l, whereas plasma lactate concentrations did not change (1.4 +/- 0.2 vs. 1.3 +/- 0.2 mmol/l). Plasma glucose concentration and glucose production did not change during alanine infusion: 4.6 +/- 0.3 vs. 4.5 +/- 0.3 mmol/l and 5.8 +/- 0.4 vs. 5.7 +/- 0.3 mg/kg/min, respectively. Gluconeogenic precursor supply is sufficient for maintainance of glucose production in African children with uncomplicated malaria who are malnourished by US standards.
Assuntos
Alanina/farmacologia , Glicemia/efeitos dos fármacos , Malária Falciparum/sangue , Distúrbios Nutricionais/sangue , Doença Aguda , Glicemia/biossíntese , Glicemia/metabolismo , Criança , Pré-Escolar , Citocinas/sangue , Feminino , Hormônios/sangue , Humanos , Malária Falciparum/complicações , Masculino , Distúrbios Nutricionais/complicaçõesRESUMO
The disposition of intramuscular artemether (AM) was studied in 26 Kenyan children with cerebral malaria. Antimalarial activity determined by bioassay was compared with total plasma AM plus dihydroartemisinin (DHA) determined by high power liquid chromatography (HPLC). Therapeutic levels were achieved in most subjects (21/26) within 1 h of receiving intramuscular AM (3.2 mg/kg), with close correlation between bioassay and HPLC measurements (r = 0.706). However, there was marked inter-individual variation, antimalarial activity was undetectable in 5 subjects ('non-absorbers'), and plasma concentrations were lower in subject with respiratory distress. The 50% parasite clearance time was significantly longer in non-absorbers (mean = 13.1 h, SD = 10.8 vs. mean = 7.8 h, SD = 5.5; P = 0.013). We conclude that the bioavailability of intramuscular AM in children with severe malaria may be highly variable, particularly in the presence of respiratory distress, and may be associated with an inadequate therapeutic response.
Assuntos
Antimaláricos/sangue , Artemisininas , Malária Cerebral/sangue , Sesquiterpenos/sangue , Antimaláricos/administração & dosagem , Antimaláricos/farmacocinética , Artemeter , Disponibilidade Biológica , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Lactente , Injeções Intramusculares , Quênia , Malária Cerebral/tratamento farmacológico , Masculino , Insuficiência Respiratória/complicações , Sesquiterpenos/administração & dosagem , Sesquiterpenos/farmacocinética , Fatores de Tempo , Resultado do TratamentoRESUMO
Data were prospectively collected on 306 Kenyan children, including blood gases in 258 (75%). Severe malaria caused a predominantly high-anion-gap metabolic acidosis in at least 43% of children. Children with coma and respiratory distress (CM + RD) had greater evidence of renal dysfunction, lower mean pH and higher mean plasma osmolality than those with respiratory distress (RD) or coma (CM) as isolated findings (mean urea 10.7 vs. 6.0 vs. 4.3 mmol/l; mean creatinine 97 vs. 74 vs. 58 mumol/l; mean osmolality 301 vs. 288 vs. 283 mosmol/l; and mean pH 7.16 vs. 7.29 vs. 7.39, respectively, p < 0.001 for each comparison of CM + RD vs. RD or CM). In addition, children with CM + RD had a higher mean blood lactate (6.7 vs. 3.3 mmol/l, p < 0.001), a lower mean haemoglobin (5.5 vs. 7.0 g/dl, p = 0.002) and a lower mean age (26.4 vs. 41.9 months, p < 0.001) than children with CM and accounted for 15/24 (63%) of all deaths. These and previous data implicate hypovolaemia and renal impairment in the pathogenesis of metabolic acidosis in severe childhood malaria. In children who are acidotic, anaemia is strongly associated with lactic acidaemia and may therefore contribute to its pathogenesis. These data also imply that coma in acidotic children (CM + RD) and those with an isolated encephalopathy (CM) may result from quite different pathophysiological mechanisms.
Assuntos
Acidose/etiologia , Malária Falciparum/complicações , Fatores Etários , Pré-Escolar , Coma/complicações , Feminino , Hemoglobinas/análise , Humanos , Lactente , Ácido Láctico/sangue , Malária Cerebral/complicações , Malária Falciparum/sangue , Malária Falciparum/terapia , Masculino , Estudos Prospectivos , Insuficiência Respiratória/complicações , Fatores de Risco , Resultado do TratamentoRESUMO
The causes of death and neurological sequelae in African children with cerebral malaria are obscure. Intracranial pressure (ICP) was monitored and cerebral perfusion pressure (CPP) calculated in 23 Kenyan children with cerebral malaria. Four children had severe intracranial hypertension (ICP > 40 mm Hg, CPP < 40 mm Hg): two died, one with an ICP of 158 mm Hg and signs of transtentorial herniation, the other one with an ICP of 42 mm Hg and cardiorespiratory arrest. The other two survived with severe neurological sequelae. Nine had intermediate intracranial hypertension (ICP > 20 mm Hg, CPP < 50 mm Hg) and 10 had mild intracranial hypertension (maximum ICP 10-20 mm Hg); all survived without severe sequelae. Mannitol controlled the ICP in children with intermediate intracranial hypertension, but it did not prevent the development of intractable intracranial hypertension in children with severe intracranial hypertension. Intracranial hypertension is a feature of Kenyan children with cerebral malaria and severe intracranial hypertension is associated with a poor outcome.
Assuntos
Malária Cerebral/complicações , Pseudotumor Cerebral/etiologia , Criança , Pré-Escolar , Diuréticos Osmóticos/uso terapêutico , Humanos , Quênia , Manitol/uso terapêutico , Pseudotumor Cerebral/tratamento farmacológicoRESUMO
The pathophysiology of hypoglycaemia in children with acute falciparum malaria, a frequent and serious complication, is unknown due to absence of data on glucose kinetics. We investigated the correlation between basal glucose production and plasma glucose concentration in 20 children (8 girls) with acute, uncomplicated falciparum malaria by infusion of [6,6-2H2]glucose. Median plasma glucose concentration was 4.5 (range 2.1-6.5) mmol/L and the median glucose production 5.0 (range 4.1-8.4) mg/kg/min. There was a positive correlation between basal glucose production and plasma glucose concentration (r = 0.53, P = 0.016). There was no correlation between the rate of glucose production and the plasma concentrations of alanine, lactate, counter-regulatory hormones or cytokines. It was concluded that, in children with acute uncomplicated falciparum malaria, endogenous glucose production is an important determinant of plasma glucose concentration, contrary to previous findings in adults with malaria, in whom peripheral uptake seems to be more important than glucose production in determining plasma glucose concentration.
Assuntos
Glucose/metabolismo , Malária Falciparum/metabolismo , Alanina/sangue , Glicemia , Catecolaminas/sangue , Criança , Pré-Escolar , Citocinas/sangue , Feminino , Glucose/biossíntese , Humanos , Hidrocortisona/sangue , Ácido Láctico/sangue , Masculino , Hormônios Pancreáticos/sangueRESUMO
We have prospectively collected information during resuscitation in 24 children with life-threatening malaria. All had clinical respiratory distress and 16 were severely anemic (hemoglobin < or = 5 g/dL) on admission. Central venous pressure (CVP) measurements were normal (< or = 5 cm of water) prior to treatment but all had a metabolic acidosis. The geometric mean lactate level was significantly higher in children admitted with severe anemia than in those without severe anemia (11.2 mmol/l versus 4.2 mmol/l; P = 0.009). Hypovolemia (a CVP on admission < 0 cm of water) was associated, although not significantly, with a higher admission plasma creatinine concentration (94 mumol/l versus 64 mumol/l; P = 0.06) and probably contributed to the severely reduced creatinine clearances (0-39 ml/min/1.73 ml2) found in 12 of the 13 children in whom this was assessed in the first 24 hr. Treatment resulted in a rapid decrease in blood lactate in 16 of the 13 children in whom this was assessed in the first 24 hr. Treatment resulted in a rapid decrease in blood lactate in 16 of the 20 children transfused, which was most dramatic in severely anemic children, who were rapidly resuscitated. In nonanemic children, early and rapid administration of normal saline usually resulted in both metabolic and clinical improvement. However, in three children, two of whom died, acidosis persisted despite resuscitation. Metabolic acidosis often accounts for respiratory distress in life-threatening childhood malaria. Severe anemia and hypovolemia appear to play major roles in its pathogenesis, are readily treatable, and there appears to be little risk of congestive cardiac failure even with an aggressive approach to fluid replacement.
Assuntos
Transfusão de Sangue , Malária Falciparum/terapia , Insuficiência Respiratória/terapia , Acidose/parasitologia , Anemia/parasitologia , Pressão Venosa Central , Pré-Escolar , Creatinina/análise , Creatinina/metabolismo , Humanos , Lactente , Rim/fisiologia , Lactatos/análise , Lactatos/metabolismo , Malária Falciparum/complicações , Malária Falciparum/etiologia , Estudos Prospectivos , Insuficiência Respiratória/etiologia , RessuscitaçãoRESUMO
Despite the frequent association of respiratory symptoms and signs with malarial morbidity and mortality in sub-Saharan Africa, the value of individual symptoms and signs has rarely been assessed. We have prospectively examined the association of individual clinical findings with the summary diagnosis of respiratory distress, outcome, and the presence of metabolic acidosis in children admitted with severe malaria to a Kenyan district hospital. Respiratory distress was present in 119 of the 350 children included in the study and in 23 of the 30 deaths (relative risk = 6.5, 95% confidence interval = 2.8-14.4). The features of a history of dyspnea, nasal flaring, and indrawing or deep breathing (Kussmaul's respiration) were individually most closely associated with the summary diagnosis of respiratory distress. Of these, deep breathing, which was sensitive (91%) and specific (83%) for the presence of severe metabolic acidosis (base excess < or = -12), is the best candidate sign to represent the prognostically important syndrome of malarial respiratory distress. Therefore, it warrants further prospective evaluation in different clinical settings and areas of different malaria endemicity.
Assuntos
Acidose/parasitologia , Malária Falciparum/etiologia , Malária Falciparum/metabolismo , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/parasitologia , Criança , Pré-Escolar , Humanos , Malária Falciparum/complicações , Prognóstico , Estudos Prospectivos , Respiração , Insuficiência Respiratória/metabolismo , Insuficiência Respiratória/mortalidade , Sensibilidade e EspecificidadeRESUMO
Prolonged, multiple seizures complicate a high proportion of cases of childhood cerebral malaria, and several studies have shown an association between these and neurological sequelae. We prospectively studied 65 patients (38 female) admitted to Kilifi Hospital in 1994. Electroencephalographic recordings (EEGs) were made at 12-hourly intervals, with continuous recordings made on a cerebral function analysing monitor (CFAM). Survivors were seen one month after discharge. Cerebral computerized tomography was performed on children with neurological sequelae. Sixty-two percent of patients had seizures following admission, of whom half had an episode of status epilepticus. Fifty-two percent of seizures were partial motor, 34% generalized tonic-clonic, and 14% partial with secondary generalization. In 22%, coma appeared to be due to a prolonged postictal state. Ten children had subtle motor seizures. Posterior parieto-temporal discharges were the most common EEG finding. Seven children died, eight developed neurological sequelae, and 50 (77%) recovered fully. Status epilepticus was associated with the development of neurological sequelae. Prolonged, multiple seizures may play an important part in the pathogenesis of coma in childhood cerebral malaria, and are likely to contribute to both the morbidity and mortality of this disease.
Assuntos
Malária Cerebral/complicações , Convulsões/etiologia , Estado Epiléptico/etiologia , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Eletroencefalografia , Feminino , Seguimentos , Humanos , Lactente , Malária Cerebral/diagnóstico por imagem , Malária Cerebral/fisiopatologia , Masculino , Morbidade , Convulsões/diagnóstico por imagem , Convulsões/fisiopatologia , Estado Epiléptico/diagnóstico por imagem , Estado Epiléptico/fisiopatologia , Tomografia Computadorizada por Raios XRESUMO
We have compared the efficacy of artemether versus quinine as treatment for cerebral malaria in children in an open randomized clinical trial in Kenya. Children admitted to hospital with coma and Plasmodium falciparum parasitaemia were treated with either intramuscular artemether (3.2 mg/kg loading dose followed by 1.6 mg/kg daily) or intravenous quinine (20 mg/kg loading dose followed by 10 mg/kg every 8 h). Both drugs were well tolerated and no significant adverse effect was observed. Parasite clearance times (50% and 90%) were shorter in patients treated with artemether (median times [h], with interquartile ranges in brackets, were: 50%, 7.3 [4.2-12.4] vs. 15.5 [9-22]; 90%, 16.9 [13.2-25] vs. 28.5 [22-35]; P < 0.0001). The total mortality in 160 children with cerebral malaria was 16.25%, with no overall significant difference between the 2 treatment groups. In a subgroup of children with respiratory distress, mortality was higher in those treated with artemether (43.7% vs. 11.1%, P < 0.05). The frequency of neurological sequelae and clinical recovery times were similar in both treatment groups. We conclude that there would currently be no advantage in replacing quinine with artemether for the treatment of cerebral malaria in African children.
Assuntos
Antimaláricos/uso terapêutico , Artemisininas , Malária Cerebral/tratamento farmacológico , Quinina/uso terapêutico , Sesquiterpenos/uso terapêutico , Artemeter , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Quênia , Malária Cerebral/complicações , Masculino , Parasitemia/tratamento farmacológico , Quinina/efeitos adversos , Sesquiterpenos/efeitos adversos , Resultado do TratamentoRESUMO
Between October 1990 and November 1991 data were collected on the frequency, causes, and nature of epileptic seizures in children admitted to the paediatric ward at Kilifi District Hospital, Kenya, from a defined study area. During this period, 1324 children were studied, of whom 15.8% had seizures as part of their illness. Malaria was by far the commonest cause of seizures, accounting for 69.0%; no other single condition caused more than 4.4%. The proportion of respiratory infections complicated by seizures was 4.0% compared to 31.3% for malaria. Only 25% of malaria-related epileptic seizures were associated with cerebral malaria; the remainder were associated with otherwise uncomplicated malaria and, in this group, 84% had complex seizures, with 47% being partial and over 70% repetitive. There was no relationship with fever, with 54% of observed seizures occurring at rectal temperatures below 38 degrees C. The minimum community incidence of complex seizures in association with non-cerebral malaria was 5.8 per 1000 per year. Complex epileptic seizures in association with otherwise uncomplicated malaria are common and may be a significant cause of longer term morbidity in malaria endemic areas.
Assuntos
Epilepsia/etiologia , Malária/complicações , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Quênia , Malária Cerebral/complicações , Malária Falciparum/complicações , MasculinoRESUMO
The prevalence and likely cause of hyponatraemia in severe childhood malaria were investigated. One hundred and thirty two children, 47 of whom had cerebral malaria, were prospectively recruited and serial simple indices of fluid and electrolyte balance and renal function monitored during admission. In 55%, hyponatraemia (sodium < 135 mmol/l) was present on admission. Hyponatraemia was pronounced (sodium < or = 130 mmol/l) in 21%, and these children gained less weight during admission (mean weight gain 2.4% v 4.3%) than children with a normal sodium (135-145 mmol/l). Overall, 31% of survivors were at least moderately dehydrated on admission (5% weight gain by discharge). These children had higher plasma urea concentrations on admission (6.1 v 4.5 mmol/l) and were more acidotic (mean base excess -12.1 v -8.0) than children who were not dehydrated. There were changes in simple indices of renal function between admission and discharge in children who survived (creatinine 65.7 v 37.9 mumol/l and urea 5.5 v 1.9 mmol/l). The results suggest that dehydration is common in severe childhood malaria, that it may contribute to mild impairment in renal function, and that hyponatraemic children are less water depleted, showing appropriate rather than inappropriate secretion of antidiuretic hormone.