Cerebral Malaria

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, but Plasmodium 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 falciparum is transmitted by female Anopheles mosquitoes. In
humans, although the parasite undergoes development in the liver, it
is the erythrocytic cycle that is responsible for disease.
• The histopathological hallmark of cerebral malaria is engorgement of
cerebral capillaries and venules with parasitised red blood cells
(PRBCs) and non-paratised RBCs (NPRBCs).
• This is due to sequestration, cyto adherence and rosetting.

4. Pathophysiology
• Sequestration –accumulation of red cells containing mature forms of the
parasite (trophozoites and 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 unrousable coma
• Seizures, usually generalized and often repeated, occur in ~10% of adults
and up to 50% of children with cerebral malaria.
• On direct ophthalmoscopy retinal haemorrhages are 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 : AntiMalarial Agents
• Artesunate is 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/kg infused 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 QTc interval 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/L or 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 atleast 24hrs, 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
• artemether plus lumefantrine
• artesunate (plus clindamycin or doxycycline)
• quinine (plus clindamycin or doxycycline).

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