Malaria

Dr. Sudheer. M. D

Sr. Lecturer in Medicine

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

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

Species P.falciparum P. Vivax P.ovale P.malariae

Prepatent Period 8-25 8-27 9-17 15-30

Length of asexual

erythrocytic cycle48 hrs 48 hrs 48 hrs 72 hrs

Red Cells

ParasitizedAll Retics Retics Mature RBCs

Merozoites per

schizont8-32 12-24 4-16 6-12

Relapse from

persistent liver

infection

No Yes YesNo, but

Recrudensence

Drug resistance Yes Yes No No

Peripheral Smear Multiple rings One ring

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.

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.

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

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

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…

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.

P.Falciparum

Main mechanisms of severe disease

Cytoadherence

Rosette formation

Agglutination

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

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

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

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

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 +/-

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

Differential diagnosis

UTI

Typhoid fever

Infectious hepatitis

Dengue

Kala azar

Amebic liver abscess

Leptospirosis

Relapsing fever

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

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

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

Associated laboratory abnormalities

Hemoglobin – decreased

Leukopenia

SGOT & SGPT increased

RFT

Thrombocytopenia

Reticulocytosis

Reduced antithrombin III

Lactic acidosis

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

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

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

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

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

Prevention

Environmental Sanitation

Many WHO health programmes

Personal measures

Mosquito bed nets at night

Repellant pastes

Pyrethroids

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.

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

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

That’s all….

Thank you.