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101.
102.
Savio D. Rodrigues Mansour Karimi Lennert Impens Els Van Lerberge Griet Coussens Stijn Aesaert Debbie Rombaut Dominique Holtappels Heba M. M. Ibrahim Marc Van Montagu Jeroen Wagemans Thomas B. Jacobs Barbara De Coninck Laurens Pauwels 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(2)
103.
Moses Laman Laurens Manning Peter M. Siba Timothy M. E. Davis 《The American journal of tropical medicine and hygiene》2013,89(5):866-868
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.1
Plasmodium vivax is increasingly recognized as a cause of severe malarial illness in Oceania and parts of Asia and South America.There is limited evidence that CSF leukocytosis can also be found in patients with P. vivax malaria and altered consciousness,2,3 but these studies did not rigorously exclude co-infections with bacterial and, as in studies in Africa of cerebral malaria caused by P. falciparum,1 viral, or fungal pathogens. Febrile seizures caused by non-malarial infections may also cause CSF leukocytosis in some children4 and are a common feature of pediatric severe malaria, thus further exacerbating diagnostic uncertainties when a severely ill child seeks treatment in a malaria-endemic setting. Therefore, there is a need for a prospective study that determines whether severe pediatric malaria caused by P. falciparum or P. vivax can cause CSF leukocytosis after other infective causes of encephalopathy have been excluded and after taking prior febrile seizures into account.We studied hospitalized children in Papua New Guinea who were enrolled in a detailed observational study of severe pediatric infections conducted in coastal Madang Province where there is transmission of multiple Plasmodium species. The study was approved by the Papua New Guinea Institute of Medical Research Institutional Review Board and the Medical Research Advisory Committee of Papua New Guinea (MRAC 10.08), and parental written consent was obtained before recruitment in all cases. To rule out acute bacterial meningitis in children in Papua New Guinea, routine lumbar puncture is usually performed if a child has impaired consciousness or after febrile seizures but has no clinical evidence of increased intracranial pressure.5 Cerebrospinal fluid leukocytes at presentation were quantified by microscopic examination using the Neubauer improved chamber (BoeCo, Hamburg, Germany). When erythrocytes were present, an adjusted leukocyte count calculated as leukocytes – [erythrocytes/100] was used5 (Characteristic Cerebral malaria (n = 22) Malaria with cerebral involvement (n = 43) Malaria admissions (n = 22) P Male sex 59 63 52 0.71 Age (months) 39.5 (23–60) 35 (27.2–48) 31 (18.9–44.3) 0.73 Axillary temperature (°C) 38.4 (37.4–39) 37.9 (37.8–38.1) 37.9 (37–38.5) 0.55 Pre-hospital antipyretic use 59 54 65 0.049 Plasmodium falciparum/P. vivax/mixed-species malaria 21/0/1 37/3/3 20/0/2 – Neurologic manifestations Cerebral malaria 100 0 0 < 0.001 Impaired consciousness 0 44 0 < 0.001 Multiple seizures 36 61 0 < 0.001 Prolonged seizures 14 19 0 0.32 Focal seizures 0 5 0 0.35 CSF leukocyte count/μL 0 (0–0.35) 0 (0–0) 0 (0–0) 0.26 0 72.7 81.4 91.3 – < 5 0 0 0 – 5–9 9.1 14 0 – 10–20 13.6 4.6 8.7 – > 20 4.6 0 0 – CSF protein level ≥ 1 g/L 9 0 9 0.51 CSF glucose level < 5 mmol/L 0 0 0 – Deaths 0 0 0 –