This document discusses malaria, caused by Plasmodium parasites transmitted via Anopheles mosquitoes. It covers the parasite's lifecycle between mosquito and human hosts, types of malaria (P. falciparum, P. vivax, etc.), innate and acquired human immune responses, clinical features including cerebral malaria and relapses, diagnostic methods like blood smears, and treatment including chloroquine, ACTs, and quinine for uncomplicated or severe cases. Complications involving multiple organ systems are also outlined.

2. Introduction & epidemiology
 Tropical disease
 .

3. Aetiology & transmission
 Parasite :
plasmodum
I. P. vivax
II. P.falciparm
III. P. malariae
IV. P. ovale
V. P.knowlesi
 Vectors : anopheles
I. A. culcifacies (rural)
II. A. fluvitalis( rice fields)
III. A. stephensi (urban)
IV. A. minimus
V. A. philippinesis
VI. A. sundaicus( costal)

4. Life cycle of malarial parasite
2 HOSTS–
 DEFINITE HOST– female Anopheles-
SEXUAL PHASE
 INTERMEDIATE HOST– Human
 STAGES :
 HEPATICphase / Tissue phase
 Erythrocytic phase
:

7. RESISTANCE MECHANISMS
 INNATE RESISTANCE
Natural capacity of host to resist infection from malaria. ( which is due to
differences in surface receptors , intra erythrocytic factors or yet unknown
causes. )
In Endemic zones – repeated infection – development of resistance.
vulnerable to infection with one species – due to difference in genetic
constitution of species.

8. INNATE RESISTANCE
INTRA ERYTHROCYTIC FACTORS :
 Resist penetration of cell by merozoites- Absence of duffy Ag.-vivax
 Impede their development- HbS.
 Assist their removal by RES.
Differences in cell membrane – decides attachment/penetration of
merozoites to receptors/cells.
Hb F & Ovalocytes- resist p. falciparum

9. ACQUIRED RESISTANCE

 Sporozoites ---  Liver cells --- No immunological response
Merozoites ---  erythrocytes ---- Immunological response
 First response –  phagocytosis in spleen / hyperplastic RE cells.
 Cell mediated immunity – -> through activated macrophages
Host defence - defervescence of fever.

10. ACQUIRED RESISTANCE
 Protective antibodies against merozoites – IgM
Complement system not involved
Schizont infested cells – phagocytosed rapidly – after OPSONISATION
 Antibodies against toxins
 Antibodies and antigens may be transmitted to fetus trans placentally
 Antibodies protect while antigens / antigen-antibody complexes help to
acquire immunity.

11. Immune Evasion By Parasite :
Reasons for survival of parasite :
Antibodies against parasite may promote their survival instead of
destruction
Infection may impair antibody synthesis
Handling & processing of antigens by macrophages is impaired
Sporozoites , schizonts & gametocytes are not destroyed by immune
system.

12. immunopathology
Anaemia
 Disproportionate to the damage to RBCs by parasite.
 Formation of autoantibodies to RBCs & immune binding or adherence of
circulating Ag-Ab complexes to uninfected RBCs.
 Hemolysis – blackwater fever – drug hypersensitivity.
 Bone marrow suppression

13. Renal damage
 Acute transient lesion as nephritis
 May progress to ARF
 ARF secondary to ATN
 Development of proteinuria over a period of 1 to
2 weeks
 ARF is reversible
 Chronic progressive nephritic syndrome
 Secondary to P. malariae infections
 Soluble immune complexes deposits in
BM of Glomerular capillaries – glomerular
lesions

14. SPLENOMEGALY
 Splenomegaly – elevated levels of IgM & Lymphocytosis in peripheral blood ,
bone marrow & liver sinusoids.
 Sequestration of RBC.
 Splenectomy – Relapse of latent infection.

15. CEREBRAL MALARIA

 Pre school children
 Common in PEM
 Plugging of cerebral capillaries with infected erythrocytes with
char CYTOADHERENCE properrty.
 Hemorrhages
 Deposition of fibrin in vessels
 Altered capillary permeability
 Intravascular coagulation

16. Clinical features

17. High risk patients –
depressed level of consciousness with
deep coma.
seizures
Irregular resp.
Hypoxia
Orthostatic Hypotension
Tachycardia
JAUNDICE, PUL. OEDEMA, RENAL
FAILURE- RARE.
Dehydration
Hypoglycemia
Metabolic acidosis
Hyperkalemia

18.  Children > 2 months (non immune ) – symptoms vary widely
 Low grade fever to temp of 104 F with headache, drowsiness
 Anorexia, nausea, vomiting, diarrhoea
 Pallor, cyanosis
 Splenomegaly
 Hepatomegaly
 Anaemia , Thrombocytopenia

19. Incubation period & stages of malaria
 P. falciparum: 9 – 14 days
 P. vivax: 12-17 days
 P. ovale: 16 – 18 days
 P. malariae: 18 – 40 days
 Onset – sudden with fever , headache ,
loss of appetite , lassitude , pain in
limbs.
 Initially – continuous or remittent fever
 Later stages – classically remittent
fever

20. Clinical pattern in endemic zones
 Atypical
 Tolerance leading to less parastitemia
 Mild symptoms
 After sometime – inherited immunity ->( due to continuous heavy exposure
leading to poor immunological defence) –> severe form of disease->Cerebral
malaria Death/ Re-development of tolerance
 Chronic malaria with marked HEPATOSPLENOMEGALY in highly endemic
zones.

21. Relapse & recrudescence
 Recrudescence/ re occurrence/ late rx failure – reappearance of asexual
parasites with in 28 days of treatment
Optimising the drug therapy/ change to alt . Regimens wil be the cure.
 Recurrence/true relapse - persistence of hypnozoite forms in liver in which
erythrocytic schizogony commences again.
 Falciparum malaria – rare relapse
(since erythrocytic schizogony does not lead to exoerythrocytic phase.)
Vivax malaria – frequent relapse
(since erythrocytic schizogony can be started in these plasmodia)

22. complications
Cerebral malaria
Anemia
Gastrointestinal illness
Algid malaria
Blackwater fever
Renal lesions
Splenic rupture
Hypoglycemia
Hyperpyrexia
Convulsions
Spontaneous bleeding &
coagulopathy
Aspiration pneumonia

23. Cerebral malaria
 Most common non-traumatic encephalopathy
 Adhering of P. falciparum infected erythrocytes to
brain capillaries causing coma & death.
 key events influencing the disease were identified
as:
PfEMP-presentation,
 platelet activation and
astrocyte dysfunction
 Pathophysiology :
 Sequestration
 Haemostasis dysfunction
 Systemic inflammation
 Neuronal damage

24.  It is manifested by coma or confusion.
 Cerebral malarial fever d/d:
menigititis , encephalitis , head injury or tetanus
on investigation on examination
CSF is normal. splenomegaly

25. anaemia
It is common in severe malaria.
 Causes:
Haemolysis of infected & uninfected
erythrocytes.
Dyserythropoiesis./ BM DEPRESSION
Splenomegaly causing erythrocyte
sequestration & hemodilution.
Depletion of folate stores.

27. Gastrointestinal illness
 Marked vomiting in infants
 Diarrhoea
 Dehydration
 Dyselectrolytemia
 Dark green or brownish stools tinged with blood
 Symptoms relieved on antmalarial therapy

28. Algid malaria
 It is charectorised by pheripheral circulatory failure and shock.
 Usually occurs with falciparum inf in non immune children
Circulatory collapse – low BP , hypodermia , rapid thready pulse
Abdominal pain , vomitting , diarrhoea may be seen
Adrenal damage – congested , necrotic , haemorrhagic on post mortem

29. Blackwater fever
 Sudden severe hemolysis
 Hemoglobinuria
 Renal failure
 Caused by hypersensitivity to antimalarial
drugs.
 Nowadays – rare due to development of
synthetic drugs.
Repeated falciparum infection
Hypersensitivity
 Anti erythrocyte antibodies&
Intravascular haemolysis
 RBCs destroyed rapidly
 Haemoglobinaemia & haemoglobinuria

31. Hypoglycaemia
 It is a frequent complication of falciparum malaria.
It can occur due to various mechanisms:
Failure of hepatic gluconeogenesis.
Increased consumption of glucose by host & parasite.
Treatment with quinine results in stimulation of pancreas to
secrete insulin. The resulting hyperinsulinaemia causes
hypoglycaemia.

32. jaundice
 It occurs due to severe hemolysis
& hepatic involvement.
 Rare in children

33. Spontaneous bleeding
&
Disseminated intravascular coagulation
Clinical manifestation include:
 haematemesis or malaena
bleeding gums
 epistaxis
petechiae
subconjuctival h’ages

34. INVESTIGATIONS

35. Blood Film Examination
Thick and thin blood films (or “smears”) have remained the gold
standard for the diagnosis of malaria. The films are stained and
examined by microscopy.
• Thick blood film -
• detecting malaria:
• a larger volume of blood is examined
• detection of even low levels of parasitaemia
• determining parasite density
• monitoring the response to treatment.
• Romanowski stains(fields, giemsa,)
 Thin blood film –
 parasite morphology
 species of Plasmodium.
 Fixed with methanol n giemsa

36. Appearance of P. falciparum in thin blood films
Ring forms or trophozoites;
many red cells infected – some
with more than one parasite
Gametocytes (sexual
stages); After a blood meal,
these forms will develop in
the mosquito gut

37. Other methods of diagnosis of malaria
 Quantitative Buffy coat test:-
 It involves staining of the centrifuged & compressed red cell layer
with acridine orange & its examination under UV light source.
 Fast, easy & more sensitive than thick smear examination, abt
60microlitres of blood from a finger, ear, or heel puncture is
sufficient.
 The parasites contain DNA which takes up acridine orange stain,
fluorescing parasites can be observed at the RBC/WBC interface
using standard white light microscope

38. Rapid diagnostic tests:-
 Detects malarial antigens (PfHRP2/PMA/pLDH) from asexual &/or sexual forms of
the parasite.
 Detected by colour changes on the antibody coated lines on the strip test such as
optiMAL assay and para sight F test are being increasingly employed.
 optiMAL:- immunochromographic test that can be performed with a drop of finger
stick blood,
 Detects LDH (parasite glycolytic enzyme) produced by all species of metabolizing
plasmodium parasites
 The detection limit of test is >100-200 parasites/ microL for P.falciparum & P.vivax
 Positive test indicates presence of viable parasitemia.

39. Polymerase chain reaction:-
 Highly sensitive and specific test for detecting all species of malaria,
particularly in cases of low level parasitemia and mixed infections
 10 fold more sensitive than microscopy

40. Other investigations:-
Complete blood counts
 Blood levels of glucose
 Bilirubin
 Urea
 Creatinine
Transaminases
 prothrombin time
 urine analysis may be done as required.

41. DIFFERENTIAL DIAGNOSIS
EARLY PHASE :
 Typhoid fever
 Non icteric
hepatitis
 Septicemia
PAROXYSMAL
PHASE :
 U.T.I.
 Gm. –Ve
Septicemia
 Liver abscess
CEREBRAL MALARIA:
 Meningitis
 Encephalitis
 Lead encephalopathy
 Heat stroke
GASTROINTESTINAL ILLNESS:
 Non specific gastroenteritis
 Cholera
 E. coli diarrhoea
 Abdominal emergencies

42. ALGID MALARIA:
 Shock due to septicaemia
CHRONIC MALARIAL FEVER WITH SPLENOMEGALY:
 Tuberculosis
 Kala azar
 Leukemia

43. TREATMENT

45. Uncomplicated P. vivax malaria
CHLOROQUINE:
10mg/kg stat followed by 10mg/kg 24, 5 mg/kg at 48 hrs total 25mg/kg
PRIMAQUINE :
 o.25mg/kg 14 days
(relapse prevention)
• Frequent relapse: 0.5-0.75mg/kg primaquine
• No role with quinine/ sp regimen

46. uncomplicated P. falciparum malaria
 No role for chloroquine
 ACT THERAPY - RX OF CHOICE.
 Artesunate 4mg/kg oral for 3 days
+
Sulfodoxine 25mg/kg& pyrimethamine 1.25mg/kg as single dose (or)

artemeether + lumefantrine ( 20mg& 120 mg) pre formulated tablets six tablets tice daily for 3
days according to weight
+
Single dose of primaquine (0.75mg/kg)

47. Multidrug resistant p. falciparum un compl.(
to CQ & SP)
 Quinine
10mg/kg orally 3 times a day for 7 days
+
• Tetra cycline (4mg /kg 4 times a day for 7 days) or
• doxycycline ( 3.5mg/kg once a dsay for 7 days) or
• Clindamycin( 20mg/kg /day two divided doses)

48. CRITERIA FOR SEVERE/COMPLI. MALARIA
 Acidosis – Base excess < -8 / HCO3 <15 meq
 Parasitemia – low int. areas : > 2%
High stable trans .areas : >5%
 Coma : Glassgow coma scale ≤ 8
 Hypoglycemia : blood glucose level <2.2
mmol/ L(<40mg%)
 Renal dysfunction : UO < 0.5ml/kg/hr.
 Pulmonary oedema( radiologially)
 Hyperlactatemia: lactate> 5 m mol/li
 Haemoglobinuria & Hb<5g.dl/ pcv<15%
CLINICAL:
 Impaired conciousness/coma
 Prostration
 Failure to feed
 Multiple convulsions(>2/24hrs)
 Acidotic breathing
 Circulatory collapse(SBP <50mm )
 Clinical jaundice/ other otrgan dysfunction
 Abnormal spon. bleeding

49. Complicated / severe malaria
 QUININE:
20mg/kg of quinine salt in 10 ml of dns/ isotonic sol. Over 4 hrs f/w
10mg/ kg over 2 hrs repeated 8th hrly til he takes orally then orally for 7 days.
(+) single dose of primaquine
 ARTESUNATE:
2.4 mg/kg iv stat then 12 & 24hrs FOLLOWED by oral combination with
artemeether + lumefantrine for 7 days.

50. Supportive therapies
 Antibiotics:- tetracycline, doxycycline etc..,
 Anticonvulsants:-
 should be administered for seizures lasting more than 5mins,
 benzodiazepines-mostly used,
 other anticonvulsants-paraldehyde, phenytoin, phenobarbitone, fosphenytoin, etc,
Blood transfusions is life saving in severe malarial anemia
Exchange transfusions has thought to benefit patients with high parasite count
  rationale is
 to remove parasite burden,( >20%)
 to reduce antigen load,
 to remove parasite derived toxins and metabolites and
 to correct anemia.

51. Dialysis:- indicated in case of acute renal failure due to severe
falciparum malaria,
 Rapidly raise of creatinine level-most sensitive indicator.
Inotropic support:- shock- algid malaria,
Dopamine is used
 Send blood culture and start on iv antibiotics.
Hypoglycemia:-
 any blood sugar <40mg/dL should be treated with 5ml/kg of 10% dextrose IV
Raised intracranial pressure:- mannitol
Ventilation:-

52. Prevention