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GUIDELINES FOR CEREBRAL
MALARIA

DR SANKALP MOHAN
SENIOR RESIDENT
NEUROLOGY
Global burden of malaria
GLOBALLY 300 MILLION MALARIA CASES A YEAR
Malaria epidemiology
Indian scenario
 Mortality most often due to P. falciparum

P. 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)
Life cycle
Section of brain showing blood vessels
blocked with developing
P. falciparum parasites
Incubation period
P. vivax and P. ovale
13~15 days
P. malariae 24~30
days
P. falciparum 7~12
days
CLINICAL FEATURES
PRODROMAL PHASE

FEBRILE PHASE
COMPLICATIONS –
CEREBRAL MALARIA
WHAT IS CEREBRAL MALARIA?
 Most clinicians consider any manifestation

of cerebral dysfunction in a patient with
malaria as cerebral malaria.
CAUSES OF CNS DYSFUNCTION IN
MALARIA
• HYPOGLYCEMIA
• HIGH GRADE FEVER ALONE
• RENAL FAILURE
• HEPATIC FAILURE

• SEPTICEMIA
• SHOCK
CEREBRAL MALARIA FEATURES
 IMPAIRMENT OF CONSIOUSNESS –DELERIUM

STUPOR,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.
DEFINITION OF CEREBRAL
MALARIA
Coma Scale for Children
Best Motor response

Verbal Response

Eye Movements

Localizes painful stimulus
Withdraws limb from pain
Non-specific or Absent
response
Appropriate Cry
2
Moan or Inappropriate cry
None
Directed
(e.g. follows mother’s face)
Not directed

Total

2
1
0
1
0
1
0

0-5
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
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,
DIAGNOSIS
 Demonstration of asexual form of P. falciparum in

peripheral blood smear, in thick and thin blood smear
films stained by Giemsa stain.
LIGHT MICROSCOPY
 Thick blood film-

enhanced sensitivity , low levels of parasitemia

-Thin blood film.- identification of the parasite to the
species level
PL FALCIPARUM RINGS

PL FACIPARUM GAMETOCYTES
Schizont stage –p
vivax

TROPHOZOITE PF
Recommendations
 At least 3 smears 6 h apart should be examined.

before excluding cerebral malaria.
 Parasitological confirmation of the diagnosis of

malaria provided by high-quality microscopy
or, where this is not available, by RDTs is
recommended for all suspected cases of malaria
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)
CSF EXAMINATION
-Necessary to exclude other causes of febrile
encephalopathy.
-CSF is generally normal in cerebral
malaria, however, mild pleocytosis (10–50 cells/mm3)
and protein rise up to 200 mg/dL may be seen.
 CT and MRI are usually normal or show edema and

cortical 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
TREATMENT
 Neurologic emergency requiring urgent

intervention.
 In endemic area, treatment should be started without
waiting for confirmation of the diagnosis
SPECIFIC THERAPY

TREATMENT OF MULTI
ORGAN DYSFUNCTION
TREATMENT OF
COMPLICATIONS
UNCOMPLICATED FALCIPARUM
MALARIA
 ACT options now recommended for treatment of

uncomplicated falciparum malaria
 artemether plus lumefantrine,

 artesunate plus amodiaquine,
 artesunate plus mefloquine,
 artesunate plus sulfadoxine-pyrimethamine,

 dihydroartemisinin plus piperaquine.
 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,
 Artemether plus lumefantrine:

standard tablets containing 20 mg of artemether and
120 mg of lumefantrine given twice a day for 3 days

Artesunate 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.
 Non-artemisinin based combination therapy

sulfadoxine-pyrimethamine plus chloroquine (SP+CQ)
or amodiaquine (SP+AQ)
- PROVEN TO BE INFERIOR

Artemisinins should not be used as
monotherapy, as this will promote resistance
P VIVAX AND MIXED INFECTION
 P.vivax -Chloroquine for 3 days and Primaquine for 14

days
 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.
TREATMENT OF SEVERE
FALCIPARUM MALARIA
 Severe malaria should always be treated

with parenteral antimalarials
 Drug of choice for cerebral malaria parenteral artemisinin derivatives or
quinine because of widespread resistance
to chloroquine.
QUININE
 it should never be given as a push INTRAVENOUS
 a continuous and uniform flow of IV quinine in

dextrose 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.
 Patients with cardiac disease and in older people, QTc

interval should be monitored
 Quinine should be discontinued if QTc interval
exceeds 25% of the basal value.
ARTESUNATE
 Artesunate has been reported to reduce mortality by

34.7% 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
 Mefloquine is not preferred for cerebral

malaria 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
SUPPORTIVE MANAGEMENT
 Hydration by administration of fluids
 Oral fluids should be given if the patient is conscious

and can swallow.
 High fever should be reduced by the use of oral
paracetamol and tepid water sponging
MANAGEMENT OF
COMPLICATIONS
 INTENSIVE CARE UNIT
 VENTILATORY SUPPORT
 HEMODIALYSIS
MANGEMENT OF COMPLICATIONS
 severe anaemia
 renal failure
 pulmonary oedema,
 shock

 spontaneous bleeding,
 repeated generalized convulsions
 acidemia or acidosis
MALARIA IN PREGNANCY
 Pregnant women in the first trimester with

uncomplicated 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
Cerebral  malaria

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Cerebral malaria

  • 1. GUIDELINES FOR CEREBRAL MALARIA DR SANKALP MOHAN SENIOR RESIDENT NEUROLOGY
  • 2. Global burden of malaria GLOBALLY 300 MILLION MALARIA CASES A YEAR
  • 4. Indian scenario  Mortality most often due to P. falciparum P. 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)
  • 6.
  • 7.
  • 8.
  • 9.
  • 10. Section of brain showing blood vessels blocked with developing P. falciparum parasites
  • 11. Incubation period P. vivax and P. ovale 13~15 days P. malariae 24~30 days P. falciparum 7~12 days
  • 12. CLINICAL FEATURES PRODROMAL PHASE FEBRILE PHASE COMPLICATIONS – CEREBRAL MALARIA
  • 13. WHAT IS CEREBRAL MALARIA?  Most clinicians consider any manifestation of cerebral dysfunction in a patient with malaria as cerebral malaria.
  • 14. CAUSES OF CNS DYSFUNCTION IN MALARIA • HYPOGLYCEMIA • HIGH GRADE FEVER ALONE • RENAL FAILURE • HEPATIC FAILURE • SEPTICEMIA • SHOCK
  • 15. CEREBRAL MALARIA FEATURES  IMPAIRMENT OF CONSIOUSNESS –DELERIUM STUPOR,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.
  • 17. Coma Scale for Children Best Motor response Verbal Response Eye Movements Localizes painful stimulus Withdraws limb from pain Non-specific or Absent response Appropriate Cry 2 Moan or Inappropriate cry None Directed (e.g. follows mother’s face) Not directed Total 2 1 0 1 0 1 0 0-5
  • 18. 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
  • 19. 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,
  • 20. DIAGNOSIS  Demonstration of asexual form of P. falciparum in peripheral blood smear, in thick and thin blood smear films stained by Giemsa stain.
  • 21. LIGHT MICROSCOPY  Thick blood film- enhanced sensitivity , low levels of parasitemia -Thin blood film.- identification of the parasite to the species level
  • 22. PL FALCIPARUM RINGS PL FACIPARUM GAMETOCYTES
  • 24. Recommendations  At least 3 smears 6 h apart should be examined. before excluding cerebral malaria.  Parasitological confirmation of the diagnosis of malaria provided by high-quality microscopy or, where this is not available, by RDTs is recommended for all suspected cases of malaria
  • 25. 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)
  • 26. CSF EXAMINATION -Necessary to exclude other causes of febrile encephalopathy. -CSF is generally normal in cerebral malaria, however, mild pleocytosis (10–50 cells/mm3) and protein rise up to 200 mg/dL may be seen.
  • 27.  CT and MRI are usually normal or show edema and cortical 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
  • 28. TREATMENT  Neurologic emergency requiring urgent intervention.  In endemic area, treatment should be started without waiting for confirmation of the diagnosis
  • 29. SPECIFIC THERAPY TREATMENT OF MULTI ORGAN DYSFUNCTION TREATMENT OF COMPLICATIONS
  • 30. UNCOMPLICATED FALCIPARUM MALARIA  ACT options now recommended for treatment of uncomplicated falciparum malaria  artemether plus lumefantrine,  artesunate plus amodiaquine,  artesunate plus mefloquine,  artesunate plus sulfadoxine-pyrimethamine,  dihydroartemisinin plus piperaquine.
  • 31.  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,
  • 32.
  • 33.  Artemether plus lumefantrine: standard tablets containing 20 mg of artemether and 120 mg of lumefantrine given twice a day for 3 days Artesunate 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.
  • 34.  Non-artemisinin based combination therapy sulfadoxine-pyrimethamine plus chloroquine (SP+CQ) or amodiaquine (SP+AQ) - PROVEN TO BE INFERIOR Artemisinins should not be used as monotherapy, as this will promote resistance
  • 35. P VIVAX AND MIXED INFECTION  P.vivax -Chloroquine for 3 days and Primaquine for 14 days  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.
  • 37.  Severe malaria should always be treated with parenteral antimalarials  Drug of choice for cerebral malaria parenteral artemisinin derivatives or quinine because of widespread resistance to chloroquine.
  • 38.
  • 39.
  • 40. QUININE  it should never be given as a push INTRAVENOUS  a continuous and uniform flow of IV quinine in dextrose 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.
  • 41.  Patients with cardiac disease and in older people, QTc interval should be monitored  Quinine should be discontinued if QTc interval exceeds 25% of the basal value.
  • 42. ARTESUNATE  Artesunate has been reported to reduce mortality by 34.7% 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
  • 43.  Mefloquine is not preferred for cerebral malaria 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
  • 44. SUPPORTIVE MANAGEMENT  Hydration by administration of fluids  Oral fluids should be given if the patient is conscious and can swallow.  High fever should be reduced by the use of oral paracetamol and tepid water sponging
  • 45. MANAGEMENT OF COMPLICATIONS  INTENSIVE CARE UNIT  VENTILATORY SUPPORT  HEMODIALYSIS
  • 46. MANGEMENT OF COMPLICATIONS  severe anaemia  renal failure  pulmonary oedema,  shock  spontaneous bleeding,  repeated generalized convulsions  acidemia or acidosis
  • 47. MALARIA IN PREGNANCY  Pregnant women in the first trimester with uncomplicated 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