1. CEREBRAL MALARIA

2. Introduction to malaria
• MALARIA IS AN PRTOZOAL DISEASE TRANSMITTED BY
BITE OF INFECTED FEMALE ANOPHELES MOSQUITOES.
• THE MOST IMPORTANT OF THE PARASITIC DISEASES OF
HUMANS.
• IT IS TRANSMITTED IN 108 COUNTRIES CONTAINING 3
BILLION PEOPLE.
• AND CAUSES NEARLY 1 MILLION DEATHS EACH YEAR.
• MALARIA HAS BEEN ELIMINATED FROM UNITED STATES,
CANADA, EUROPE AND RUSSIA ; HOWEVER ITS
PREVELANCE ROSE IN MANY PARTS OF THE TROPICS.

3. MALARIATHREATENS 40% WORLD
POPULATION

4. ETIOLOGYAND PATHOGENESIS
• 5 SPECIES OF THE GENUS PLASMODIUM CAUSE
NEARLY ALL MALARIAL INFECTIONS IN HUMANS .
• THESE ARE P.FALCIPARUM, P. VIVAX, P . OVALE, P.
MALARIAE, AND IN SOUTH EAST ASIA THE MONKEY
MALARIAL PARASITE P. KNOWLESI
• ALLMOST ALL DEATHS ARE CAUSED BY
FALCIPARUM MALARIA

5. • Although p. vivax and p. malariae had achieved the
widest global distribution, today p . Malariae has lost its
predominance and p. vivax and p. falciparum are the most
commonly encountered malaria parasites.
• P. vivax is now the most geographically widespread of the
human malarias, estimated to account for 100-300 million
clinical cases across much of asia , central and south
america , the middle east and parts of africa , where 70-
90% of the malaria burden of p. vivax species and the rest
due to p.falciparum.

6. Malaria in India
• The state of orissa, with a population of 36.7 million
contributes to 25% of the total annual malaria cases more
than 40% of p. falciparum malaria cases and nearly 20-
30% deaths caused by malaria in india , followed by
meghalaya, mizoram, maharastra, rajastan, gujarat,
karnataka, goa, southern madhya pradesh, chattisghar,
and jharkhand that also report significant number of
malarial cases and deaths.
• The proportion of p.vivax and p.falciparum varies in
different parts of india although p. falciparum accounts for
<10% of malaria cases in mostly indogangetic plains and
northern hilly states , northwestern india , and southern
tamil nadu , it causes 30-90% of the infections in the
forested areas inhabited by ethnic tribes.

8. HOST RESPONSE
• INITIALLY, THE HOST RESPONDS TO PLASMODIAL
INFECTION BY ACTIVATING NONSPECIFIC DEFENSE
MECHANISMS.
• SPLENIC IMMUNOLOGIC AND FILTRATIVE CLEARANCE
FUNCTIONS ARE AUGMENTED IN MALARIA, AND THE
REMOVAL OF BOTH PARASITIZED AND UNINFECTED
ERYTHROCYTES IS ACCELERATED.
• THE GENETIC DISORDERS LIKE SICKLE CELL DISEASE,
HEMOGLOBINS C AND E, HEREDDITARY OVALOCYTOSIS,
THE THALASSEMIAS, AND GLUCOSE 6 PHOSPHATE
DEHYDROGENASE DEFICIENCY CONFER PROTECTION
AGAINST DEATH FROM FALCIPARUM MALARIA.
• IMMUNE INDIVIDUALS HAVE A POLYCLONAL INCREASE IN
SERUM LEVELS OF IGM, IGG AND IGA.

9. CLINICAL FEATURES
• NONSPECIFIC SYMPTOMS::LACK OF SENSE OF WELL
BEING, HEADACHE, FATIGUE, ABDOMINAL DISCOMFORT,
AND MUSCLE ACHES FOLLOWED BY FEVER.
• HEADACHE IS MORE SEVERE IN MALARIA, THERE IS NO
NECK STIFFNESS OR PHOTOPHOBIA AS OCCURS IN
MENINGITIS.
• NAUSEA, VOMITTING, AND ORTHOSTATIC HYPOTENSION
ARE COMMON.
• THE CLASSICAL MALARIAL PAROXYSMS, IN WHICH
FEVER SPIKES, CHILLS, AND RIGORS OCCUR AT
REGULAR INTERVALS.
• THE TEMPERATURE OF NONIMMUNE INDIVIDUALS AND
CHILDREN OFTEN RISES ABOVE 40 C IN CONJUNCTION
WITH TACHYCARDIA AND SOMETIMES DELIRIUM.
• ANAEMIA,PALPABLE SPLEEN AND LIVER AND MILD
JAUNDICE ARE COMMON.

10. • In P.falciparum infection, fever can occur every third day,
or more frequently, even in a daily paroxysmal pattern.
• The typical malarial paroxysm occurs in a sequence of
chills and fever followed by sweating, often described as
cold, hot and wet stages respectively.

11. Comparision of the 5 plasmodium species
causing human malaria
• P.falciparum :: in india 30-90% cases in orissa,the
northeastern states chattisghar, jharkhand, MP, bihar and
andamans.
• Pre-erythrocytic cycle :: 5-6 days
• Incubation period :: 12 days
• Exoerythrocytic phase :: absent
• Merozoites per tissue schizont :: 40,000
• Erythrocytic cycle :: 48 hours
• Fever pattern :: tertian, subtertian
• Relapses :: +
• Period of recurrence :: short
• Severe malaria :: 6%

12. • P.vivax :: in india, nearly 50% of total malaria burden;
predominant species in most parts other than P.falciparum
dominant areas.
• Pre-erythrocytic cycle:: 8 days
• Incubation period:: 13 days or upto 6-12 months
• Merozoites per tissue schizont :: more than 10,000
• Fever pattern :: tertian
• Relapses:: ++
• Severe malaria :: 3%

13. • P.ovale::stray cases reported from kolkata, orissa, delhi,
gujarat, and assam
• Pre-erythrocytic cycle:: 9 days
• Incubation period:: 17 days or longer
• Merozoites per tissue schizonts:: 15,000
• Fever pattern :: tertian
• Severe malaria :: very rare
• Relapse:: ++

14. • P.malaria:: in india , 3-16% reported from some tribal
areas, particularly orissa.
• Pre-erythrocytic cycle:: 13 days
• Incubation period:: 28 days or longer
• Merozoites per tissue schizonts :: 2000
• Fever pattern :: quartan
• Severe malaria :: very rare
• Relapses::+++

15. PATHOGENESIS OF
COMPLICATED
PLASMODIUM
FALCIPARUM
ERYTHROCYTE CHANGES IN P.
FALCIPARUM MALARIA

16. • IN P.FALCIPARUM INFECTIONS, MEMBRANE
PROTRUBERANCES APPEAR ON THE
ERYTHROCYTES SURFACE 12-15 HOUR AFTER THE
CELL INVASION.
• THESE KNOBS EXTRUDE A HIGH MOLECULAR
WEIGHT, ANTIGENICALLY VARIANT, STRAIN SPECIFIC
ERYTHROCTE MEMBRANE ADHESIVE PROTEIN THAT
MEDIATES ATTACHMENT TO RECEPTORS ON
VENULAR AND CAPILLARY ENDOTHELIUM AND IS
CALLED AS CYTOADHERENCE.

17. • SEVERAL VASCULAR RECEPTORS HAVE BEEN
IDENTIFIED, OF WHICH INTRACELLULAR ADHESION
MOLECULE 1(ICAM 1) IS PROBABLY THE MOST
IMPORTANT IN THE BRAIN, CHONDROITIN SULPHATE
B IN THE PLACENTA, AND CD 36 IN MOST OTHER
ORGANS
• THUS, THE INFECTED ERYTHROCYTES STICK
INSIDE AND EVENTUALLY BLOCK CAPILLARIES AND
VENULES.
• AT THE SAME STAGE, THESE P. FALCIPARUM
INFECTED RBC MAY ALSO ADHERE TO UNINFECTED
RBC’S TO FORM ROSETTES AND TO OTHER
PARASITIZED ERYTHROCYTES.

18. c

19. MANIFESTATION OF SEVERE
FALCIPARUM MALARIA
• COMA OR CEREBRAL MALARIA
• ACIDEMIA/ACIDOSIS
• SEVERE NORMOCHROMIC,NORMOCYTIC ANEAMIA
• RENAL FAILURE
• NON CARDIOGENIC PULMONARY OEDEMA/ ARDS
• HYPOGLYCEMIA
• HYPOTENSION/SHOCK
• BLEEDING/DIC
• CONVULSIONS
• HEMOGLOBINURIA/black water fever.

20. DEFEINITION OF CEREBRAL MALARIA
• WHO DEFINITION:: UNROUSABLE COMA NOT
ATTRIBUTABLE TO ANY OTHER CAUSE IN A PATIENT
WITH FALCIPARUM MALARIA.
THE COMA SHOULD PERSIST FOR ATLEAST 30 MIN
AFTER A GENERALISED CONVULSION TO
DIFFERENTIATE FROM THE TRANSIENT POST ICTAL
COMA.
• EXCLUSION OF OTHER CAUSES OF COMA (
HYPOGLYCEMIA, BACTERIAL MENINGITIS, VIRAL
ENCEPHALITIDES )

21. AETIOPATHO
GENESIS
SEQUESTRATION OF
CEREBRAL
CAPILLARIES AND
VENULES

22. MECHANICAL
HYPOTHESIS
P.FALCIPARUM
PARASITES IN BRAIN
CAPILLARIES

23. SECTION OF BRAIN SHOWING BLOOD
VESSELS BLOCKED WITH
DEVELOPING P.FALCIPARUM
PARASITES

24. • SELECTIVE CYTOADHERENCE RESULTS IN
ROSETTING
• REDUCTION OF MICROVASULAR BLOOD FLOW
• HYPOXIA

25. HUMORAL HYPOTHESIS
• MALARIAL TOXIN
• STIMULATES PRODUCTION OF TNF-ALPHA AND
CYTOKINES
• STIMULATE ENDOTHELIAL CELLS
• UNCONTROLLED PRODUCTION OF NITRIC OXIDE
• COMA

27. Charecteristics of cerebral malaria
• Coma is charecteristic and ominous feature of falciparum
malaria.
• Onset may be sudden following seizures or gradual with
initial drowsiness, confusion, disorientation, delirium, or
agitation.
• Extreme agitation is indication of poor prognosis in
falciparum malaria.
• Diffuse symmetric encephalopathy; focal nuerological
signs are unusual.

28. Cont..
• On routine fundoscopy, 15% of patients have retinal hemorrhages.
Other fundoscopic abnormalities include discrete spots of retinal
opacification, papilledema,cotton wool spots, and decolouration of a
retinal vessels or segment of vessel.
• On examination :: patient is febrile and unrousable . Although some
passive resistance to head flexion may be detected, signs of
meningeal irritation is absent.
• Bruxism is present.
• Brisk jaw reflex present.
• Cranial nerves usually normal.
• Pout reflex is common.
• The corneal reflexes are preserved, except in deep coma.
• Muscle tone may be increased or decreased; plantar reflexes may be
flexor or extensor.
• Patients may have a increase in tone with extensor posture of
decorticate or decerebrate.
• Ophisthotonus posture.

29. Post malarial neurological syndromes
• Late neurological complications may occur following
recovery from cerebral malaria.These are psychosis,
encephalopathy, parkinsonian rigidity, tremors, cerebellar
dysfunction.

30. RELATIVE INCIDENCE OF SEVERE
COMPLICATIONS OF FALCIPARUM
MALARIA
COMPLICATION NONPREGNANT
ADULTS
PREGNANT
WOMEN
CHILDREN
ANEMIA + ++ +++
CONVULSIONS + + +++
HYPOGLYCEMIA + +++ +++
JAUNDICE +++ +++ +
RENAL FAILURE +++ +++ -
PULMONARY
OEDEMA
++ +++ +

31. Features indicating poor prognosis
• Clinical: marked agitation, hyperventilation(respiratory
distress),hypothermia(<36.5), bleeding, deep coma, repeated
convulsions, anuria, shock.
• Laboratory : Biochemistry : Hypoglycemia, hyperlactatemia,
acidosis, elevated serum creatinine, elevated total bilirubin,
elevated liver enzymes, elevated muscle enzymes, elevated
urate.
• Hematology : leukocytosis, severe anemia, decreased platelet
count (<50000), prolonged prothrombin time, prolonged partial
thromboplastin time, decreased fibrinogen.>5% neutrophils
contain visible malarial pigment.
• Parasitology : Hyperparasitemia,>20% of parasites identified as
pigment containing trophozoites and schizonts.

32. Relapse in malaria
• A latent stage for Plasmodium spp. in the liver, for which
there is now extensive morphological and experimental
confirmation, best explains both the relapse phenomenon
and the long prepatent periods seen with some strains of
Plasmodium vivax.
• These latent stages (hypnozoites) have been detected in
three relapsing malarias and have been found to persist in
the liver as uninucleate parasites for up to 229 days after
sporozoite inoculation.

33. DIAGNOSIS OF FALCIPARUM
MALARIA
• The thin blood smears should be rapidly air dried,
fixed and stained.
• The thick blood smears ; the thick film has the
concentrating advantage and thus increasing
diagnostic sensitivity

34. STAGES OF P.FALCIPARUM

35. LAB DIANOSIS
• Fluorescence Microscopy (QBC)
• Nucleic Acid Staining with acridine
• Parasite Count = (TLC / Cuml X Parasite / 100
WBC) / 100 = Parasite / Cuml of Blood
• Serology
• Anti body detection
• Antigen detection
• Biochemical Test - Optimal test (Parasite LDH)
• PCR & Culture

36. Rapid malaria test
SD BIOLINE Malaria rapid test (P.f/p.v) is a qualitative
immunochromatographic rapid test for detection of
antibodies of all isotypes (IgG, IgM, IgA) specific to
Plasmodium falciparum and Plasmodium vivax
simultaneously in human serum, plasma or whole blood.

38. CEREBRAL INVOLVEMENT
• Clinical
• CSF - Increased Lactic Acid and low glucose;
mild increase in cell count(leukocyte
pleocytosis with lymphocyte predominance)
and raised protein concentration(>50 mg/dl)
• CT, MRI

39. THERAPEUTIC OPTIONS
•CHEMOTHERAPY
•Quinine
•Artemisinins - Artesunate
• - Arte- ether
• - Arte - mether

40. Antimalarial drugs for severe malaria
Parentral antimalarial immediately
on admission for atleast 24 hours
• First choice: artesunate
2.4mg/kg iv stat, after 12 hours and
then once daily.
• Alternative: quinine
20mg/kg iv infusion stat, upto
maximum of 1.4 g quinine can be
given over 4 hours, then 10mg/kg 8
hourly iv/im, then orally for totally 7
days.
• Alternative: artemether
3.2mg/kg im stat, then 1.6 mg/kg per
day
Follow on complete treatment
• Full course of
artesunate+SP or
artesunate plus
amodiaquine or artesunate
plus clindamycin or
doxycycline for 7 days.
• Doxycycline 3.5mg/kg od for
7 days (not in pregnancy
and children<8 years)or
clindamycin 10 mg/kg bd for
7 days.
• Full course of
artemether+lumefantrine

41. Radical cure of malaria due to p.vivax and
p.ovale
• Relapses can be prevented by primaquine (15mg daily for
14 days ), which destroys the hypnozoite phase in liver.
• Malaria in pregnancy : uncomplicated P.falciparum :
• First trimester : quinine + clindamycin for 7
days(artesunate + clindamycin for 7 days if this fails or if
nothing else available)
• Second and third trimesters : ACT being used in the
country/region or artesunate + clindamycin for 7 days or
quinine + clindamycin for 7 days.
• Severe malaria : parenteral artesunate, artemether, or
quinine.

42. Chemoprophylaxis of malaria
Area Antimalaria
tablets
Adult
prophylactic
dose
Regimen
Choloroquine
resistance high
Mefloquine or
doxycycline or
malarone
250 mg
100 mg
1 tablet from 1-2
days before
travelling to 1
week after return
One tablet weekly
Daily
Daily
Chloroquine
resistance
moderate
Chloroquine plus
proguanil
150 mg base
100 mg
2 tablets weekly
2 tablets weekly
Chloroquine
resistance absent
Chloroquine or
proguanil
150 mg
100 mg
2 tablets weekly
1 or 2 tablets daily

43. SUPPORITIVE &
ADJUNCTIVE THERAPY
• Nursing Care
• Catherization
• Nasogastric tube
• Fluid & Electrolyte
• Monitor level of coma & vital signs
• Antipyretics
• Anticonvulsants
• Reduction in ICT
• Correction of Hypoglycemia
• Exchange Transfusion
• Increase Microcirculatory Flow - Pentoxyfylline
• Desferrioxamine
• Correction of - Anaemia, Acidosis, Dehydration

44. NEWER HORIZON
•Inhibition of Endothelial Activity
•- LMP 420 – inhibitor of TNF alpha
& LT activity
•Vaccine Development

45. Prevention
• Avoid mosquito bites.
• Mosquito repellant.
• Insecticide mosquito nets.
• Preventive medicines: Chloroquine is taken weekly and is
the preferred drug for the few areas without chloroquine
resistance, it's used in combination with proguanil in areas
with a slightly higher risk of chloroquine-resistant
malaria.Doxycycline and malorone.
• Both chloroquine and proguanil have no special risk for
pregnant women and should be administered together.

46. Outcome of cerebral malaria
• Cerebral malaria carries a mortality of about 20% in adults
as well as children and most deaths occur within 24 hours
of admission, even before antimalarial drugs have had
time to work.
• Cerebral malaria and transtentorial herniation leading to
respiratory arrest and severe metabolic acidosis causing
cardio respiratory arrest have been identified as some of
causes of death.
• The mortality was 39.28% among pregnant women.

47. Thank you 