Malaria

1. Malaria
Dr. Sudheer. M. D
Sr. Lecturer in Medicine

2. Introduction
 Most important human parasitic
disease
 ≈ 170 million cases annually
 ≈ over 1 million death, mostly in
Africa
 Resurgent for last 2 decades
 Resistant Falciparum presently a
problem in India

3. Parasitology
 > 100 species of plasmodia
 Only 4 have humans as their vertebrate
host
 P. vivax, P.falciparum, P.ovale, P.malaria
 Zoonotic Malaria – P.knowlesi, P.simium,
P.cynomolgi

4. Species P.falciparum P. Vivax P.ovale P.malariae
Prepatent Period 8-25 8-27 9-17 15-30
Length of asexual
erythrocytic cycle
48 hrs 48 hrs 48 hrs 72 hrs
Red Cells
Parasitized
All Retics Retics Mature RBCs
Merozoites per
schizont
8-32 12-24 4-16 6-12
Relapse from
persistent liver
infection
No Yes Yes
No, but
Recrudensence
Drug resistance Yes Yes No No
Peripheral Smear Multiple rings One ring

5. Host Factors
 In hyperendemic areas
 People are infected with a high
systemic protozoal load
 Fever may not occur unless
individual’s immunity is hampered
 In mesoendemic or hypoendemic areas
 Infection is usually associated with
febrile episodes and clinical malaria.

6. Host genetic factors
 People in Africa are naturally resistant to
Pl. vivax due to absence of Duffy factor
surface antigen.
 Contribute to response to Quinine and
occurrence of adverse effects of Quinine.

7. Source of cases
1. Imported Malaria
2. Transmitted malaria
 From indigenous cases
 During festivals from people visiting from
endemic areas
3. Indigenous malaria
4. Induced Malaria
 Blood Transfusion, needle stick, nosocomial
 Congenital and neonatal
5. Zoonotic malaria

10. Pl.vivax
 Most common cause of Malaria in humans
 Produce classic clinical features
 Single ring forms in RBCs
 Chloroquin resistance is a problem in India
 Mixed infections of vivax and falciparum very
common

11. Pl. falciparum
 Severe infection and associated with life
threatening complications
 Different modes of clinical
 No periodicity for fever as for Pl. vivax
 No cryptobiotic phase in the liver
 Recrudescence…

12. Pathogenesis of Pl.falciparum
 Immune injury to RBC leads to Knobs on
RBCs PfEMP1 protein
 RBCs easily adhere to endothelium
 Clogging of RBC in microcirculation- in
various tissues
 Complications of Pl.falciparum attributable to
these organ injuries.

13. P.Falciparum
 Main mechanisms of severe disease
 Cytoadherence
 Rosette formation
 Agglutination

14. Complications of Pl.falciparum Malaria
 Cerebral malaria – with edema
 Hyperpyrexia
 Hemolytic anemia
 ARDS
 Acute tubular necrosis and ARF – dark urine –
black water….massive intravascular hemolysis
with Quinine treatment
 Acute hepatopathy
 Centrilobular necrosis and marked jaundice
but no liver failure

15. Anemia in malaria
 HEMOLYSIS
 Hemolysis of parasitized red cells
 Hemolysis of noninfected red cells
 Splenic and reticuloendothelial hyperactivity
 Oxidative stress
 Host genetic factors
 Drug induced
 MARROW SUPPRESSION
 Abnormalities of erythroid progenitors
 Impaired erythropoiesis
 Malarial pigment
 Serum erythropoietin

16.  Hypoglycemia
 Adrenal insufficiency
 Cardiac Dysrrhythmias
 Secretory diarrhoea
 Lactic acidosis
 Water & Electrolyte imbalance
 Co-existing pneumonia
 Rare – Burkitt’s Lymphoma – Burkitt noted the
Association
 Pl.malariae- Nephrotic syndrome in adults years
later.
Complications of Pl.falciparum Malaria

17. Poor prognostic factors
 Multiple complications at presentation
 Shock, Bleeding, Deep Coma, Hypothermia,
hyperventilation
 Hypoglycemia < 45 mg/dl, hyperlactatemia >5
mmol/L
 Creatinine >3.5, SGOT SGPT > 3 times normal
 Severe anemia - PCV < 15%
 Parasite load > 100,000 /µL
 > 20% of infected RBC contain mature parasite
 > 5% of Neutrophils contain pigment
 Associated Gram - Negative sepsis

18. Clinical Presentations
 Typical h/o –
 Recently returned from an endemic zone
 Paroxysms of fever
 3 Stages –
 Stage I – High grade fever
 Stage II – Chills & Rigor – lasts 1-2 hrs
 Stage III - sweating
 Splenomegaly, pallor, jaundice +/-

19. Periodicity of malarial fever
Day 1 Day 2 Day 3 Day 4
Quartan- Day 1- - 4
Tertian – Day 1 - 3
Quotidian – Everyday
Benign Tertian
Malignant Tertian

20. Differential diagnosis
 UTI
 Typhoid fever
 Infectious hepatitis
 Dengue
 Kala azar
 Amebic liver abscess
 Leptospirosis
 Relapsing fever

21. Remember….May be a D/D of….
 Comatose patient from an endemic area
 Febrile comatose pt. with hypoglycemia and pallor
 Meningococcal septicaemia
 Leptospirosis with hepatorenal syndrome +/-
ARDS
 Fever with hypotension – algid malaria

22. Chronic Complications of Malaria
 Anemia – normocytic normochromic
 Contributes to malnutrition
 Tropical Splenomegaly
 Quartan Malarial Nephropathy
 FSGS
 Subendothelial deposits
 Poor response to Rx
 Burkitt’s lymphoma

23. Laboratory diagnosis
 Peripheral Smear – Thick and Thin smear
 Negative Smear does not rule out malaria
 Repeat smears ideally just before the peak of
fever
 If negative Repeat smears for 2 days 24 hr apart
 Thick and thin smear – Giemsa at pH 7.2
 Rapidly air dried and fixed in anhydrous
methanol
 RBCs at the tail of film examined with oil
immersion
 Quantitative Buffy Coat

25. Associated laboratory abnormalities
 Hemoglobin – decreased
 Leukopenia
 SGOT & SGPT increased
 RFT
 Thrombocytopenia
 Reticulocytosis
 Reduced antithrombin III
 Lactic acidosis

26. Serology
 Antibodies detectable only 8-10 days after onset of
symptoms
 Does not distinguish between current and past
infection
 Cross reactivity with other antigens like Leptospira
and Salmonella
 Triple Antigen test
 Diagnostic Stick test – Pf HRP2 –remains +ve for
several weeks after infection
 PCR

27. Treatment
 Chloroquin sensitive Malaria
 Chloroquin Phosphate – 25 mg base/kg
 250mg tabs have 150mg base
 4 tablets stat
4 tablets 24 hrs later – i.e. on day 1
2 tablets 48 hrs later – i.e. on day 2
 Primaquin Sulphate
 15 mg given for 5 days – Pl.vivax
 45 mg given as single dose– Pl. falciparum

28. Treatment –other drugs
 Chloroquin resistant Malaria
 Quinine – 10 mg/kg 3 times daily X 3-7 days
600 mg given TDS
 Plenty of Oral Glucose to be taken
 In cerebral malaria – 20 mg/kg iv Quinine till
pt could take orally then 10 mg /kg orally
 A/E – hyperinsulinemia hypoglycemia
Cardiac Arrhythmias , QT prolongation
hypotension

29. Chloroquin resistant Pl. falciparum..
 Quinine + one of following
 Doxycycline 100 mg BD X 7 days
 Clindamycin – 900 mg TDS X 5 days
 Pyrimethamine – 25 mg BD X 3 days
 Sulphadiazine – 500 mg 4 times daily X 5 days
 Fansidar 3 tablets stat (pyri-75 mg + sulpha –
1500mg)
Or
 Mefloquin – 1250 mg once or
750mg stat , 500mg 6 hr later

30. Other drugs
 Atovaquone + doxycycline – 500/100 BD x 3
days
 Artesunate – 4 mg/kg/day X 3days followed by
Mefloquine 1250
 Here – 4 mg/kg /day x 3days followed by
Quinine or Doxycycline
 Halofantrine

31. Prevention
 Environmental Sanitation
 Many WHO health programmes
 Personal measures
 Mosquito bed nets at night
 Repellant pastes
 Pyrethroids

32. Prevention
 Chemoprophylaxis to travellers
 Chloroquine – 500 mg salt weekly. Single
dose weekly started 1 week before entering
endemic area and for 4 weeks after leaving
 Mefloquine – 250 mg weekly
 Doxycycline – 100 mg daily –start 2 days
before entering endemic area, while there
and for 4 weeks after leaving the area.

33. Special situtations
 Malaria in Pregnancy
 Assoc. With LBW (Low birth weight)
 Increased Infant Mortality
 Maternal HIV predispose pregnant
woman to malaria
 Severe malaria –fetal demise
 Congenital Malaria in 5 % of newborn
 Pl. vivax also produce LBW esp in
multigravida

34. Summary
 Most common parasitic disease especially in tropics
 Pl. falciparum is associated with high mortality
 Have a good index of suspicion in endemic areas
 Responds easily to treatment usually if recognized
early
 Chloroquin resistance is a present problem
 Quinine and Artesunate good drugs for Chloroquin
resistant Falciparum Malaria
 Prevention – Mosquito nets / repellants and
environmental sanitation; better than fogging DDT all
over the place

35. That’s all….

36. Thank you.