Paediatrics chapters
Cerebral malaria
The most dangerous complication of falciparum malaria in children: why it happens, how a child presents, the key tests, emergency supportive care and parenteral antimalarial treatment.
- Cerebral malaria is coma in a child with P. falciparum parasitaemia and no other cause; infected red cells become sticky and block cerebral small vessels (sequestration), causing oedema and small haemorrhages.
- A child, often under 5, has fever, convulsions and coma with pallor and splenomegaly, no neck stiffness, and often hypoglycaemia and severe anaemia; the thick and thin blood film confirms it and CSF is usually normal.
- Treat with parenteral antimalarials (quinine, artemether, or artesunate per current guidance) plus glucose, transfusion, seizure control and fluids; mortality is about 10-30% and some survivors have deficits.
On this page
Overview
Cerebral malaria is a severe form of Plasmodium falciparum malaria that presents with coma and convulsions. Akbar defines it as coma in a child with falciparum parasitaemia when no other cause of coma is found. It is the most serious complication of malaria and a frequent cause of death in children and in non-immune people. Malaria is endemic in parts of Pakistan, so any comatose febrile child from an endemic area needs a blood film.
Aetiology and epidemiology
- P. falciparum only; spread by the bite of an infected female Anopheles mosquito, and also by blood transfusion, needles, organ transplant and across the placenta.
- Incubation of falciparum malaria is about 9-14 days (Akbar's table and Nelson).
- Falciparum invades red cells of all ages, so parasite loads can be very high in non-immune children; one schizont releases the largest number of merozoites of any species.
- Cerebral malaria is more likely with heavy parasitaemia (Nelson: over 5%).
- Some host factors give partial protection: sickle cell trait, HbF, HbC and HbE, G6PD deficiency; Akbar also lists blood groups A and B.
- Infants of immune mothers are protected for the first 3-6 months by maternal antibody.
Pathogenesis
- About 8-18 hours after invasion, infected red cells develop knobs and become sticky, adhering to the endothelium of venules and capillaries (sequestration or cytoadherence), helped by ICAM-1.
- Packed vessels slow and block flow; parasites keep maturing and release merozoites locally, infecting more cells.
- Around the blocked vessels there is inflammation, ring haemorrhages and necrosis; fibrin thrombi may give a DIC-like picture.
- The result in the brain is cerebral oedema and raised pressure. Nitric oxide and immune complexes may add damage.
- Hypoglycaemia, anaemia, acidosis and seizures all worsen brain injury.
The lesion is mechanical blockage of brain small vessels by parasitised red cells, not invasion of brain tissue by parasites.
Clinical features
- Symptoms start after the incubation period of about 9-14 days.
- Young children show behaviour change first: anorexia, fretfulness, unusual crying, drowsiness, disturbed sleep; older children report headache, nausea and aches.
- Fever may rise gradually or start suddenly, with or without chills.
- Convulsions (often repeated, focal or generalised) and coma.
- Neurological signs of raised ICP and symmetrical upper motor neuron and brainstem signs: disconjugate gaze, decerebrate or decorticate posturing, opisthotonus.
- Severe pallor and splenomegaly (or hepatosplenomegaly); jaundice.
- No neck stiffness, apart from abnormal posturing.
- Retinal haemorrhages on fundoscopy.
Akbar notes the adult pattern is often not seen in children under 5 years. A high-fever child who is unconscious and convulsing, with pallor and a big spleen, in an endemic area, is the classic picture.
Other features of severe malaria (Akbar)
| Complication | Note |
|---|---|
| Severe anaemia | Haemoglobin under 5 g/dl; the commonest severe complication in children |
| Hypoglycaemia | Common; worsens coma and outcome |
| Respiratory distress | From metabolic acidosis; a poor prognostic sign |
| Multiple seizures, prostration | Prostration: cannot sit, stand or eat without help, while conscious |
| Blackwater fever | Massive haemolysis, dark urine, acute renal failure |
| Renal failure, jaundice, DIC, pulmonary oedema | Nelson also lists splenic rupture and algid malaria (shock) |
Neck stiffness is absent in cerebral malaria. A febrile comatose child with neck stiffness and turbid CSF has meningitis; both can coexist, so the CSF is still examined once the child is stable.
Investigations
| Test | Finding |
|---|---|
| Thick and thin blood films (Giemsa) | Most specific test: ring forms early, crescent-shaped gametocytes after about 10 days; up to 20% of red cells infected. Thick film screens many cells; thin film identifies the species and parasite percentage. Repeat over several days if negative |
| Rapid antigen test (ICT) | Detects parasite antigen |
| Blood glucose | Hypoglycaemia (check at once and repeatedly) |
| Blood count | Anaemia, raised reticulocytes, variable white count with monocytosis, low platelets |
| CSF | Usually normal (pressure may be raised); done to exclude meningitis |
| Electrolytes, urea, creatinine | Renal failure, acidosis |
Films may be negative if antimalarials have already been given.
The blood film is the diagnostic test; a normal CSF with a positive film in a comatose febrile child supports cerebral malaria.
Differential diagnosis
| Condition | Distinguishing points |
|---|---|
| Febrile convulsion | Age 6 months to 6 years, child rousable soon after, CSF clear, no parasites |
| Pyogenic meningitis | Toxic child, meningeal signs, turbid abnormal CSF |
| Viral encephalitis | No anaemia, no coagulopathy, no parasites; CSF may show cells and protein |
| Space-occupying lesion | Headache, vomiting, diplopia, papilloedema, focal signs; CT or MRI |
| Hepatic coma | Deep jaundice, small liver, very abnormal liver tests, clotting defect |
| Hypoglycaemic coma | Afebrile, cold and sweaty, very low glucose |
| Uraemia | Preceding oedema or diarrhoea, urinary symptoms |
Management
Supportive care
- Airway, breathing, circulation; nurse on the side; comatose care.
- Hypoglycaemia: an IV glucose bolus, then regular glucose with 10% dextrose; recheck often.
- Anaemia: transfuse if haemoglobin is below 6 g/dl (packed cells 10 ml/kg).
- Convulsions: IV diazepam (or rectal paraldehyde), then phenobarbitone (Akbar: a 10 mg/kg first dose followed by 5 mg/kg/day split into two doses).
- Fever: tepid sponging, paracetamol by nasogastric tube.
- Fluids: correct dehydration carefully, then maintenance; avoid overload because of brain and lung oedema.
- Renal failure: hydrate, reduce the antimalarial dose, dialysis if needed.
Antimalarial treatment
Give the drug parenterally until the child can swallow, then complete an oral course.
| Drug | Regimen (Akbar) |
|---|---|
| Quinine dihydrochloride IV | 20 mg/kg loading dose infused over about 4 hours, then 10 mg/kg every 8 hours, diluted in 5% dextrose; switch to oral quinine when awake |
| Artemether IM | 3.2 mg/kg stat, then 1.6 mg/kg daily; can replace quinine in severe malaria |
| Artesunate | Akbar's IMCI section names artesunate or quinine as the first dose for severe malaria before referral |
- Keep checking blood glucose throughout treatment; Akbar notes that quinine hypersensitivity may contribute to blackwater fever.
- Chloroquine is no longer reliable for falciparum because of resistance.
- Current WHO and national malaria guidelines change; check the current national guideline for the preferred drug for severe malaria (injectable artesunate is now widely preferred).
"Glucose, Blood, Benzo, then Bug": correct hypoglycaemia and anaemia and stop seizures while starting the antimalarial.
In every comatose child with malaria, check blood glucose immediately and repeatedly.
Prognosis
- Mortality: Akbar 10-30%; Nelson 20-40%. Most deaths occur within 24 hours of admission.
- Coma usually lifts within hours to a few days after treatment.
- Most survivors recover fully, but about 10% keep a permanent neurological deficit, more often after hypoglycaemia.
- Poor prognostic signs (Akbar): coma over 36 hours, repeated seizures, abnormal posture (opisthotonus, decerebrate, decorticate), conjugate eye deviation, retinal haemorrhages, low urine output and raised creatinine; also respiratory distress (acidosis) and hypoglycaemia.
- Death is more likely in children who are already ill with measles, anaemia, worms or malnutrition (Nelson).
Prevention
Mosquito nets over beds, repellents, screened rooms and clothing, and chemoprophylaxis for non-immune travellers.
Expect: P. falciparum as the only cause; sequestration of sticky red cells in brain vessels; coma and convulsions with pallor, splenomegaly and no neck stiffness; hypoglycaemia and severe anaemia; thick and thin films as the key test and normal CSF; parenteral quinine (20 then 10 mg/kg) or artemether, and artesunate in current guidance; glucose monitoring; transfusion threshold; differentiation from meningitis and febrile seizures; mortality 10-30% and residual deficits in about 10%.
Quick revision
- Falciparum only; coma with parasitaemia and no other cause.
- Sticky parasitised cells block cerebral venules: oedema, ring haemorrhages.
- Fever, fits, coma, pallor, splenomegaly; no neck stiffness; retinal haemorrhages.
- Check glucose: hypoglycaemia is common and harmful.
- Thick and thin film; CSF normal.
- IV quinine 20 mg/kg then 10 mg/kg 8-hourly, or IM artemether; artesunate per current guidance.
- Transfuse below 6 g/dl; control seizures; careful fluids.
- Mortality 10-30%; about 10% of survivors keep deficits.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Nelson Essentials of Paediatrics).
FAQ
Why does only falciparum cause cerebral malaria?
Falciparum-infected red cells become sticky and cling to the walls of small brain vessels, blocking flow. The other species do not sequester in this way.
Why is hypoglycaemia so important in cerebral malaria?
It is common, it can cause or deepen coma, and it is linked to permanent brain damage. Glucose must be checked at once and repeatedly.
Is lumbar puncture needed in a child with cerebral malaria?
The CSF is usually normal, but meningitis can look the same or coexist, so it is examined when the child is stable and there is no sign of raised pressure.
What is the outlook?
About one in ten to three in ten children die, mostly in the first day. Most survivors recover fully, but around 10% keep a neurological deficit.