1.GUIDELINES FOR CEREBRAL MALARIADR SANKALP MOHAN SENIOR RESIDENT NEUROLOGY

2. Global burden of malaria GLOBALLY 300 MILLION MALARIA CASES A YEAR 3. Malaria epidemiology 4. Indian scenario Mortality most often due to P. falciparumP. vivax (50-55%) P. falciparum (48-52%) P. malariae (small #, foothills of Orissa) P. ovale (not found) 95% of pop. live in malaria risk areas 90% of malaria unstable (low incidence and epidemics every 7-10 yrs) 5. Life cycle 6. Section of brain showing blood vessels blocked with developing P. falciparum parasites 7. Incubation period P. vivax and P. ovale 13~15 days P. malariae 24~30 days P. falciparum 7~12 days 8. CLINICAL FEATURES PRODROMAL PHASEFEBRILE PHASE COMPLICATIONS CEREBRAL MALARIA 9. WHAT IS CEREBRAL MALARIA? Most clinicians consider any manifestationof cerebral dysfunction in a patient with malaria as cerebral malaria. 10. CAUSES OF CNS DYSFUNCTION IN MALARIA HYPOGLYCEMIA HIGH GRADE FEVER ALONE RENAL FAILURE HEPATIC FAILURE SEPTICEMIA SHOCK 11. CEREBRAL MALARIA FEATURES IMPAIRMENT OF CONSIOUSNESS DELERIUMSTUPOR,OBTUNDATION ,COMA SIEZURES FOCAL/GENERALISED (COMMONER IN CHILDREN ) MENINGISMUS FOCAL NEUROLOGIC SIGNS(LESS COMMON)(aphasia, hemiplegia, ataxia, chorea, and tremor) neuro-ophthalmologic signs (gaze deviation, oculomotor palsy, nystagmus, and ocular bobbing) -Retinal hemorrhage may occur in 15% of patients. 12. DEFINITION OF CEREBRAL MALARIA 13. Coma Scale for Children Best Motor responseVerbal ResponseEye MovementsLocalizes painful stimulus Withdraws limb from pain Non-specific or Absent response Appropriate Cry 2 Moan or Inappropriate cry None Directed (e.g. follows mothers face) Not directedTotal2 1 0 1 0 1 00-5 14. SEQUALE Transient neurologic sequelae ataxia, hemiparesis, memory disturbance, visual field defects, cognitive impairment, and behavioral abnormalities A postmalaria neurological syndrome characterized by acute onset of confusion, seizure, ataxia, myoclonus, tremor, and aphasia 15. PROGNOSTIC FACTORS the level of consciousness presence of other organ dysfunction Recurrent seizures, decerebration, retinal hemorrhage, age < 3 years, heavy parasitemia, (>20%), lactic acidosis, elevated CSF lactate serum transaminase, 16. DIAGNOSIS Demonstration of asexual form of P. falciparum inperipheral blood smear, in thick and thin blood smear films stained by Giemsa stain. 17. LIGHT MICROSCOPY Thick blood film-enhanced sensitivity , low levels of parasitemia-Thin blood film.- identification of the parasite to the species level 18. PL FALCIPARUM RINGSPL FACIPARUM GAMETOCYTES 19. Schizont stage p vivaxTROPHOZOITE PF 20. Recommendations At least 3 smears 6 h apart should be examined.before excluding cerebral malaria. Parasitological confirmation of the diagnosis ofmalaria provided by high-quality microscopy or, where this is not available, by RDTs is recommended for all suspected cases of malaria 21. OTHER DIAGNOSTIC TESTS -DETECTION OF MALARIAL ANTIGENS 1.Pl Glutamate Dehyrogenase 2.Pl Falciparum HRP II- only in Falciparum 3. Pl LDH - DIAGNOSIS USING FLUORESCENCE MICROSCOPY -Fluorescent dyes have an affinity for the nucleic acid in the parasite nucleus (ACRIDINE ORANGE) 22. CSF EXAMINATION -Necessary to exclude other causes of febrile encephalopathy. -CSF is generally normal in cerebral malaria, however, mild pleocytosis (1050 cells/mm3) and protein rise up to 200 mg/dL may be seen. 23. CT and MRI are usually normal or show edema andcortical or subcortical infarcts in watershed zone in 15%20% patients. EEG shows nonspecific abnormalities, such as diffuse slowing, spike wave discharges, and burst suppression pattern 24. TREATMENT Neurologic emergency requiring urgentintervention. In endemic area, treatment should be started without waiting for confirmation of the diagnosis 25. SPECIFIC THERAPYTREATMENT OF MULTI ORGAN DYSFUNCTION TREATMENT OF COMPLICATIONS 26. UNCOMPLICATED FALCIPARUM MALARIA ACT options now recommended for treatment ofuncomplicated falciparum malaria artemether plus lumefantrine, artesunate plus amodiaquine, artesunate plus mefloquine, artesunate plus sulfadoxine-pyrimethamine, dihydroartemisinin plus piperaquine. 27. Artesunate plus sulfadoxine-pyrimethamine containing 50 mg of artesunate and tablets containing 500 mg of sulfadoxine and 25 mg of pyrimethamine Therapeutic dose- artesunate given once a day for 3 days and a single administration of sulfadoxinepyrimethamine on day 1, 28. Artemether plus lumefantrine:standard tablets containing 20 mg of artemether and 120 mg of lumefantrine given twice a day for 3 daysArtesunate plus tetracycline or doxycycline or clindamycin These are reserved for very rare occasions of treatment failures to the recommended ACTs Any of these combinations should be given for 7 days. 29. Non-artemisinin based combination therapysulfadoxine-pyrimethamine plus chloroquine (SP+CQ) or amodiaquine (SP+AQ) - PROVEN TO BE INFERIORArtemisinins should not be used as monotherapy, as this will promote resistance 30. P VIVAX AND MIXED INFECTION P.vivax -Chloroquine for 3 days and Primaquine for 14days Chloroquine: 25 mg/kg body weight divided over three days i.e. 10mg/kg on day 1, 10mg/kg on day 2 and 5mg/kg on day 3. Treatment of mixed infections (P.vivax + P.falciparum) cases: course of ACT and Primaquine 0.25 mg per kg body weight daily for 14 days. 31. TREATMENT OF SEVERE FALCIPARUM MALARIA 32. Severe malaria should always be treatedwith parenteral antimalarials Drug of choice for cerebral malaria parenteral artemisinin derivatives or quinine because of widespread resistance to chloroquine. 33. QUININE it should never be given as a push INTRAVENOUS a continuous and uniform flow of IV quinine indextrose solution should be maintained over a period of four hours require monitoring of pulse, blood pressure, and blood glucose. IM injection carries the risk of necrosis at the injection site and the injection is very painful. 34. Patients with cardiac disease and in older people, QTcinterval should be monitored Quinine should be discontinued if QTc interval exceeds 25% of the basal value. 35. ARTESUNATE Artesunate has been reported to reduce mortality by34.7% compared to quinine in a randomized controlled trial in Asian adults. Artemether and artesunate are advantageous because of low toxicity, ease of administration Artesunate, which is water soluble has the advantage of i.v. or im. administration Does not produce hypotension or hypoglycemia 36. Mefloquine is not preferred for cerebralmalaria because of neuropsychiatric complication Corticosteroids are not beneficial IN cerebral malaria BENEFICIAL IN POST MALARIA SYNDROME Phenobarbitone reduces the seizures, it increases mortality specifically in children 37. SUPPORTIVE MANAGEMENT Hydration by administration of fluids Oral fluids should be given if the patient is consciousand can swallow. High fever should be reduced by the use of oral paracetamol and tepid water sponging 38. MANAGEMENT OF COMPLICATIONS INTENSIVE CARE UNIT VENTILATORY SUPPORT HEMODIALYSIS 39. MANGEMENT OF COMPLICATIONS severe anaemia renal failure pulmonary oedema, shock spontaneous bleeding, repeated generalized convulsions acidemia or acidosis 40. MALARIA IN PREGNANCY Pregnant women in the first trimester withuncomplicated falciparum malaria should be treated with quinine plus clindamycin for seven days artemisinin derivatives in the second and third trimesters Primaquine and tetracyclines should not be used in pregnancy