cerebral-malaria-190410002220-1.pdfxxxxx

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1. Cerebral Malaria

2. Introduction
•Malaria remains one of the most prevalent infectious diseases in the world.
•The World Health Organization (WHO) reports that 50% of the world’s
population living in 109 countries are still at risk of malaria
•Cerebral malaria is the most severe pathology caused by the malaria
parasite, Plasmodium falciparum.
•There are four species of human malaria, butPlasmodium falciparum
causes nearly all the deaths and neurological complications.
•Coma is a characteristic and ominous feature of falciparum malaria and,
despite treatment, is associated with death rates of ~20% among adults
and 15% among children

3. Pathophysiology
•P falciparumis transmitted by female Anopheles mosquitoes. In
humans, although the parasite undergoes development in the liver, it
is the erythrocyticcycle that is responsible for disease.
•The histopathological hallmark of cerebral malaria is engorgement of
cerebral capillaries and venuleswith parasitisedred blood cells
(PRBCs) and non-paratisedRBCs (NPRBCs).
•This is due to sequestration, cytoadherence and rosetting.

4. Pathophysiology
•Sequestration–accumulation of red cells containing mature forms of the
parasite (trophozoitesand meronts) in the microvasculature of organs (most
commonly the brain) secondary to cyto-adherence and rosetting
•Cyto-adherence-a specific interaction between PRBCs and the vascular
endothelium mediated by plasmodium derived proteins on the surface of
PRBCs and modified erythrocyte cell wall proteins on endothelial cells.
•The adhesion of the PRBCs reduces the microvascular blood flow,which may
explain organ and tissue dysfunction such as coma.
•Rosetting-The adherence of NPRBCs to PRBCs results in agglutination within
microvasculature also contributing to ischemia and organ damage.

6. Clinical Manifestations
•Cerebral Malaria can occur in less than two weeks after a mosquito bite
and may develop after 2 to 7 d of fever.
•Can begin as AMS or delirium and progress to unrousablecoma
•Seizures, usually generalized and often repeated, occur in ~10% of adults
and up to 50% of children with cerebral malaria.
•On direct ophthalmoscopy retinal haemorrhagesare found in about 15% of
patients
•Signs of multi-organ failure include jaundice, metabolic acidosis and acute
pulmonary edema.
•Hypoglycemia is common along with anemia.
•Rarely, patients with severe malaria have disseminated intravascular
coagulation

7. Diagnosis
•The diagnosis of malaria rests on the demonstration of asexual forms of
the parasite in stained peripheral-blood smears.
•Giemsa at pH 7.2 is the preferred stain
•Both Thick and Thin Blood Smears should be taken and fixed appropriately
•THICK FILM = advantage of concentrating the parasites (by 40-to 100-fold
compared with a thin blood film) and thus increasing diagnostic sensitivity.
•THIN SMEAR = Determine level of parasitemia(quantify as # of infected
RBC per 1000 RBCs)
•Rapid, simple, sensitive, and specific antibody-based diagnostic stick or
card tests that detect P. falciparum–specific Malaria

8. Lab Findings
•Anemia= usually normochromic, normocytic
•WBC = elevated in cerebral malaria; with reactive lymphocytosis and eosinophilia
in the weeks after the acute infection.
•ESR/CRP elevated
•Severe infections may be accompanied by prolonged prothrombin and partial
thromboplastin times and by more severe thrombocytopenia.
•Hypoglycemia, and metabolic acidosis may be present with electrolyte imbalance.
•the mean cerebrospinal fluid (CSF) Findings
•opening pressure at lumbar puncture is ~160 mm;
•usually the CSF content is normal
•or there is a slight elevation of total protein level (<1.0 g/L [<100 mg/dL]) and cell count
(<20/μL).

9. Management : AntiMalarialAgents
•Artesunateis the drug of choice for all patients with severe malaria
everywhere.
•Artesunate(2.4 mg/kg stat IV followed by 2.4 mg/kg at 12 and 24 h and then daily if
necessary) OR
•Artemether(3.2 mg/kg stat IM followed by 1.6 mg/ kg qd)
•Quinine dihydrochloride(20 mg of salt/kginfused over 4 h, followed by 10
mg of salt/kg infused over 2–8 h q8hr)
•The administration of quinidine must be closely monitored if dysrhythmias
and hypotension are to be avoided.
•If total plasma levels exceed 8 μg/mL or the QTcinterval exceeds 0.6 s or
the QRS complex widens by more than 25% of baseline, then infusion rates
should be slowed or infusion stopped temporarily.

10. Management: Supportive Care
•Severe falciparum malaria constitutes a medical emergency requir-ing
intensive nursing care and careful management.
•RBS Monitoring q 4hrly ; All patients should receive a continuous infusion
of dextrose, and blood concentrations ideally should be maintained above
4 mmol/Lor 70mg/dl.
•Blood Transfusions for severe anemia(HCT <20%)
•Patients who develop spontaneous bleeding should be given fresh blood
and IV vitamin K.
•Convulsions should be treated with IV or rectal benzodiazepines and, if
necessary, respiratory support.
•Monitor BUN and Cr and assess Fluid status daily to prevent overload.
•Patients who develop AKI or metabolic acidosis may require dialysis.

11. Follow-on treatment
•Following initial parenteral treatment for atleast24hrs, once the
patient can tolerate oral therapy, it is essential to continue and
complete treatment with an effective oral antimalarial using a full
course of an effective ACT
•artemetherplus lumefantrine
•artesunate(plus clindamycin or doxycycline)
•quinine (plus clindamycin or doxycycline).

12. References
•Harrison’s Principles of Internal Medicine 19
th
Ed.
•Medscape
•WHO’s Guidelines for the treatment of malaria, 2
nd
Ed.