Lumbar Puncture in Children from an Area of Malaria Endemicity Who Present with a Febrile Seizure

Laman, Moses; Manning, Laurens; Hwaiwhange, Ilomo; Vince, John; Aipit, Susan; Mare, Trevor; Warrel, Jonathan; Karunajeewa, Harin; Siba, Peter; Müeller, Ivo; Davis, Timothy M. E.

doi:10.1086/655679

Cited by 21 publications

(29 citation statements)

References 32 publications

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“…In resource-poor settings such as Papua New Guinea, where blood and CSF cultures, as well as facilities to enable appropriate clinical and laboratory monitoring may not be available, the presence of CSF pleocytosis should prompt consideration of diagnoses other than severe malaria and empiric antimicrobial therapy in addition to antimalarial therapy. Depending on the clinical situation, 12 there may even be a case for withholding such empiric therapy in children with malaria parasites on a peripheral blood smear or a positive rapid diagnostic test result and no CSF leukocytes, and monitoring the response to antimalarial therapy alone. Second, an increased CSF leukocyte density should not be attributed to seizures, whether caused by fever or malaria, even if they are complex.…”

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confidence: 99%

Prevalence and Implications of Cerebrospinal Fluid Leukocytosis in Papua New Guinean Children Hospitalized with Severe Malaria

Laman¹,

Manning²,

Siba³

et al. 2013

The American Society of Tropical Medicine and Hygiene

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Abstract. Cerebrospinal fluid (CSF) leukocytosis in severe malaria was assessed in 87 children in Papua New Guinea participating in a detailed longitudinal observational study who had undergone lumbar puncture for further investigation of altered consciousness and/or convulsions. After rigorous exclusion of non-malarial infection, 16 (20.5%) of 78 children with Plasmodium falciparum monoinfection but 0 of 9 with P. vivax/mixed-species malaria had a detectable CSF leukocytosis, which was unrelated to prior, including complex, seizures. There were eight children with a CSF leukocyte density 10 cells/μL (9.2% of the total sample), half of whom had cerebral malaria (4 of 22, 18.1%). Cerebrospinal fluid leukocytosis is infrequent in severe pediatric malaria, especially in children with P. vivax infections, and it is generally mild. Its presence in a blood slide-positive child should prompt consideration of alternative diagnoses and empiric antibiotic therapy.Studies reporting cerebrospinal fluid (CSF) leukocytosis in cases of pediatric cerebral malaria have been conducted mainly in sub-Saharan Africa where Plasmodium falciparum monoinfections predominate. Approximately 10% of children with cerebral malaria and no bacteriologic evidence of acute bacterial meningitis have CSF pleocytosis of 10 cells/μL in this setting.

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Prevalence and Implications of Cerebrospinal Fluid Leukocytosis in Papua New Guinean Children Hospitalized with Severe Malaria

Laman¹,

Manning²,

Siba³

et al. 2013

The American Society of Tropical Medicine and Hygiene

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“…A positive Kernig's sign also indicates that ABM is likely. In children without these features (including those with a single febrile seizure 20 ) and who have a positive blood film for malaria, lumbar puncture and empiric antibiotic therapy with a third-generation cephalosporin could be deferred pending further investigation and monitoring after administration of antimalarial therapy. However, physical examination findings are subject to technical competence, individual interpretation, and inter-observer variability.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical signs of meningeal irritation were neck stiffness (inability to flex the neck so that the chin touched the upper chest), a positive Kernig's sign (straightening of the knee joint eliciting discomfort with the hip and knee joints flexed to 90 ), a positive Brudzinski's sign (involuntary hip flexion from 0 elicited on neck flexion), or a bulging fontanel in children < 18 months old. 20 Deep coma and impaired consciousness were defined as a Blantyre coma score (BCS) 21 2 and 4, respectively. Cerebrospinal fluid was examined by using standard methods.…”

Section: Methodsmentioning

confidence: 99%

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Predictors of Acute Bacterial Meningitis in Children from a Malaria-Endemic Area of Papua New Guinea

Laman

Manning²,

Greenhill

et al. 2012

The American Society of Tropical Medicine and Hygiene

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Abstract. Predictors of acute bacterial meningitis (ABM) were assessed in 554 children in Papua New Guinea 0.2-10 years of age who were hospitalized with culture-proven meningitis, probable meningitis, or non-meningitic illness investigated by lumbar puncture. Forty-seven (8.5%) had proven meningitis and 36 (6.5%) had probable meningitis. Neck stiffness, Kernig's and Brudzinski's signs and, in children < 18 months of age, a bulging fontanel had positive likelihood ratios (LRs) 4.3 for proven/probable ABM. Multiple seizures and deep coma were less predictive (LR ¼ 1.5-2.1). Single seizures and malaria parasitemia had low LRs ( 0.5). In logistic regression including clinical variables, Kernig's sign and deep coma were positively associated with ABM, and a single seizure was negatively associated (P 0.01). In models including microscopy, neck stiffness and deep coma were positively associated with ABM and parasitemia was negatively associated with ABM (P 0.04). In young children, a bulging fontanel added to the model (P < 0.001). Simple clinical features predict ABM in children in Papua New Guinea but malaria microscopy augments diagnostic precision.

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“…After recruitment, a standardized case report form detailing demographic information, medical history, history of the current illness, and clinical findings was completed. Venous blood was taken for malaria parasite microscopy, plasma biochemistry, and bacterial culture (27). Severe malaria was defined as malaria parasite detection on microscopy of a peripheral blood smear and one or more of the following features: (i) impaired consciousness/coma (Blantyre coma score Ͻ 5) (34), (ii) prostration (inability to sit/stand unaided), (iii) multiple seizures, (iv) hyperlactatemia (blood lactate concentration Ͼ 5 mmol/liter), (v) severe anemia (hemoglobin level Ͻ 50 g/liter), (vi) dark urine, (vii) hypoglycemia (blood glucose level Ͻ 2.2 mmol/liter), (viii) jaundice, or (ix) respiratory distress.…”

Section: Methodsmentioning

confidence: 99%

Meningeal Inflammation Increases Artemether Concentrations in Cerebrospinal Fluid in Papua New Guinean Children Treated with Intramuscular Artemether

Manning¹,

Laman²,

Page‐Sharp³

et al. 2011

Antimicrob Agents Chemother

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Although the artemisinin-associated neurotoxicity identified in vitro and in animal studies has not been confirmed clinically, only one adult study has measured cerebrospinal fluid (CSF) concentrations after administration of conventional doses. Potential artemisinin neurotoxicity could be serious in children, especially those with meningitis and, consequently, a compromised blood-brain barrier. We measured CSF/plasma artemether and dihydroartemisinin (DHA) concentrations in 32 Papua New Guinean children with a mean age of 39 months with suspected or proven severe falciparum malaria who underwent a single lumbar puncture after intramuscular artemether administration. CSF artemether concentrations were 0 to 43.5 g/liter and CSF concentration/plasma concentration ratios were 0 to 38.1%. DHA was measurable in CSF in only two children. The seven children with meningeal inflammation (CSF white cell count > 20/mm 3 ) had higher CSF artemether concentration/plasma artemether concentration ratios than those without (median, 6.7% [interquartile ratio, 2.5 to 27.8%]% versus 0.0% [interquartile ratio, 0.0 to 2.5%]; P ‫؍‬ 0.002). Meningeal inflammation was associated with a 4.6-fold increase in the CSF artemether concentration/plasma artemether concentration ratio in a population pharmacokinetic model. These data suggest that pharmacovigilance should be heightened when intramuscular artemether is given to severely ill children with evidence of meningeal inflammation.Neurotoxicity associated with artemisinin and its derivatives has been observed in vitro and in animal studies (14, 46). Brain stem neurons are particularly susceptible (8), and the duration of drug exposure is an important determinant (8, 28). On the basis of these data, short-term peak concentrations of artesunate and its active metabolite, dihydroartemisinin (DHA), after intravenous artesunate administration are considered less potentially neurotoxic than the prolonged plasma concentrations of artemether and DHA observed after intramuscular artemether administration, especially with repeated dosing (20, 28).The relevance of in vitro and animal neurotoxicity data to humans is, however, uncertain. Animal studies have involved allometrically higher doses of artemisinin drugs given for periods longer than those recommended for the treatment of human malaria (8,20,46). There are reports of cases of artemisinin-associated neurotoxicity (15,17,22,32,39), subtle hearing loss in retrospective case-control studies (47), and a suggestion of a longer recovery from coma (48, 49) in artemether-treated patients. In contrast, substantial clinical trial and observational evidence (11,12,40), as well as data from otological (25, 31) and neuropathological (10, 21) studies, has not raised safety concerns. Nevertheless, although the mortality benefits of artemisinin drugs over alternative therapies are clear (11,12), recent reviews of artemisinin-associated neurotoxicity continue to recommend pharmacovigilance, especially in potentially high-risk groups, such as children and preg...

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Lumbar Puncture in Children from an Area of Malaria Endemicity Who Present with a Febrile Seizure

Abstract: Initial LP is unnecessary when careful clinical assessment indicates features of a simple febrile seizure.

Cited by 21 publications

References 32 publications

Prevalence and Implications of Cerebrospinal Fluid Leukocytosis in Papua New Guinean Children Hospitalized with Severe Malaria

Prevalence and Implications of Cerebrospinal Fluid Leukocytosis in Papua New Guinean Children Hospitalized with Severe Malaria

Predictors of Acute Bacterial Meningitis in Children from a Malaria-Endemic Area of Papua New Guinea

Meningeal Inflammation Increases Artemether Concentrations in Cerebrospinal Fluid in Papua New Guinean Children Treated with Intramuscular Artemether

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