Admission diagnosis of cerebral malaria in adults in an endemic area of Tanzania: implications and clinical description

Makani, Julie; Matuja, William; Liyombo, Edwin; Snow, Robert W.; Marsh, Kevin; Warrell, D A

doi:10.1093/qjmed/hcg059

Cited by 96 publications

(87 citation statements)

References 22 publications

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“…34,35 In a randomized trial, insecticide-impregnated nets did not reduce mortality in Ghanaian adults, suggesting that malaria is not a major cause of death in this age group. 36 However, immunologically naive adult visitors to endemic areas are highly susceptible and major epidemics with high case fatality may occur in areas of initially low transmission to which malaria returns after having been nearly eliminated.…”

Section: Discussionmentioning

confidence: 99%

An Epidemiologic Model of Severe Morbidity and Mortality Caused by Plasmodium Falciparum

Ross

Maire

Molineaux

et al. 2006

The American Journal of Tropical Medicine and Hygiene

146

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Abstract. The intensity of Plasmodium falciparum transmission has multifarious and sometimes counter-intuitive effects on age-specific rates of severe morbidity and mortality in endemic areas. This has led to conflicting speculations about the likely impact of malaria control interventions. We propose a quantitative framework to reconcile the various apparently contradictory observations relating morbidity and mortality rates to malaria transmission. Our model considers two sub-categories of severe malaria episodes. These comprise episodes with extremely high parasite densities in hosts with little previous exposure, and acute malaria episodes accompanied by co-morbidity or other risk factors enhancing susceptibility. In addition to direct malaria mortality from severe malaria episodes, the model also considers the enhanced risk of indirect mortality following acute episodes accompanied by co-morbidity after the parasites have been cleared. We fit this model to summaries of field data from endemic areas of Africa, and show that it can account for the observed age-and exposure-specific patterns of pediatric severe malaria and malaria-associated mortality in children. This model will allow us to make predictions of the long-term impact of potential malaria interventions. Predictions for children will be more reliable than those for older people because there is a paucity of epidemiologic studies of adults and adolescents.

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Section: Discussionmentioning

confidence: 99%

An Epidemiologic Model of Severe Morbidity and Mortality Caused by Plasmodium Falciparum

Ross

Maire

Molineaux

et al. 2006

The American Journal of Tropical Medicine and Hygiene

146

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“…Bacterial, cryptococcal, and tuberculous meningitis and viral encephalitis commonly occur in PNG children in this situation (3,26,27). In addition, African studies reveal that approximately one-quarter of children diagnosed with cerebral malaria have such alternative diagnoses (45), and the proportion of adults with such alternative diagnoses appears to be substantially higher (29). Although artemether may improve the outcome from sepsis in the absence of malaria (35), our predictive modeling suggests that repeated recommended daily doses of intramuscular artemether will, in the presence of meningeal inflammation, result in accumulation to levels approaching and in some cases exceeding those resulting in significant neuronal toxicity and death in vitro (Ͼ100 g/liter) (46).…”

Section: Discussionmentioning

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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“…In several recent studies, the routine slide reading for malaria was shown to have very poor positive predictive value when compared to expert microscopy [39,40]. In one centre, only 13% of adults with diagnosis of cerebral malaria actually had parasitemia on their blood film [41]. These data suggests that over-diagnosis of clinical malaria may be widespread in India and therefore may lead to under-treatment of other life threatening conditions.…”

Section: Burden Of Neonatal Malariamentioning

confidence: 99%

Clinical Presentation and Management of Neonatal Malaria: A Review

D¹

2014

Malaria Contr Elimination

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The burden of neonatal malaria was thought rare in the past because of presence of protective factors such as maternal antimalarial antibodies, lactoferrin, secretary IgA in human milk and HbF. In endemic areas for malaria, this group (neonates) needs to be more focused for such infection, as due to difficulty in diagnosis it may be representing only the tip of iceberg. In addition there is little information on the use of artimisinin-based combination therapy in neonates. This review aims to discuss all these aspects, focusing mainly on diagnosis and management of neonatal malaria. The final objective is to emphasize the need to establish management guideline of malaria in this neglected age group.

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Admission diagnosis of cerebral malaria in adults in an endemic area of Tanzania: implications and clinical description

Cited by 96 publications

References 22 publications

An Epidemiologic Model of Severe Morbidity and Mortality Caused by Plasmodium Falciparum

An Epidemiologic Model of Severe Morbidity and Mortality Caused by Plasmodium Falciparum

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

Clinical Presentation and Management of Neonatal Malaria: A Review

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