MALARIA

INTRODUCTION

Malaria is an infectious disease caused by

protozoan of the genus Plasmodium

(P.falciparum, P.vivax, P.malariae or

P.ovale), which is transmitted by the bite

of an infected female Anophelus

mosquito. Malaria is characterised by

recurrent episodes of chills, fever,

sweating and anaemia.

Quartan malaria

Falciparum malaria

Blackwater fever

Tertian malaria

Alternative names:

EPIDEMIOLOGY Malaria is typically found in warmer regions of the

world. In tropical and subtropical climates.

Plasmodium vivax is more prevalent in India, Pakistan, Bangladesh, Sri Lanka, and Central America

P. falciparum is predominant in Africa, Haiti, Dominican Republic, the Amazon region of South America, and New Guinea.

Plasmodium ovale occur in Africa, and the distribution of Plasmodium malariae is considered worldwide.

ETIOLOGY

Malaria is caused by the bite of an infected female anopheles mosquito that introduces the sporozoites of the following:

i. Plasmodium falciparum,

ii. Plasmodium vivax

iii. Plasmodium ovale

iv. Plasmodium malariae

It can also be caused by blood transfusion in rare cases.

TRANSMISSION

• Blood tranfusions

• Organ transplants

• Shared use of needles and syrings

• Mother to fetus brfore or during delivery

Malaria can also be transmitted through

PATHOPHYSIOLOGY

2 Phases

- Human host

- Mosquito inhabitation

Animated lifecycle of the malaria parasite

1

TRANSMISSION

TO MAN

TRANSMISSION

TO MAN

LIVER

Sporozoites

Nucleus

Hypnozoite

Infected

Hepatocyte

Schizont

Merozoites

Erythrocyte

Ring

Trophozoite

Schizont

43 – 48 h

Cycle leading

to clinical

symptoms

P. vivax

dormant stage

Gametocytes

TRANSMISSION

TO MOSQUITO

Macro-

gametocyte

Macro-

gametocyte

(Exflagellation)

Diploid

Zygote

Ookinete

Oocysts

Sporozoites

15-30 mins

5.4 days

9 days

15 mins

1h

12-36h

9-12 days

DIAGNOSIS

The diagnosis of malaria may in fact into two

ways:

Direct diagnosis: Direct demonstration of the

parasite whole cell or of parasite’s nucleic

acid or products in the blood.

Indirect Diagnosis: The demonstration of the

patient’s immune response to the infection

(immunodiagnosis)

A)LIGHT MICROSCOPIC

OBSERVATION(LMO)

1) THIN FILM TEST

Observation of malarial parasites are optimal when

parasites are fixed and observed in RBCs after

appropriate staining.

Thin film has a low sensitivity and is thus

inadequate for low parasitaemic infection.

DIR

EC

T D

IAG

NO

SIS

2) THICK FILM TEST

An adequate parasite concentration method

obtained by osmotic lysis of the RBCs

releasing the parasites.

The sensitivity is more than thin film.

B) THE DIRECT ACRIDINE ORANGE

STAINING

sensitive microscopic test based on the ability

of acridine orange to stain nucleic acid

containing cells.

C) DETECTION OF P. FALCIPARUM

ANTIGEN

The production of histidine rich protein II

(HRP-II) antigen by blood stages of

Plasmodium falciparum forms the basis for the

development of ELISA antigen test.

IND

IRE

CT

DIA

GN

OS

IS

(IM

MU

NO

DIA

GN

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IS)

1) IMMUNOFLUORESCENT ASSAY

TEST (IFAT)

First serological test used for malarial

antibodies was immunofluorescence

(IFAT), which may give quantitative

results for both G and M specific

immunoglobulin.

2) Indirect Haemoagglutination Test (IHA)

Simple and suitable for field studies but its

sensitivity and specificity are poor.

3) Radioimmuno Assay (RIA)

Sometimes used but needs well equipped

research laboratories and personnel.

Known quantity of antigen is made

radioactive frequently by labelling it with gama

radio active isotopes of iodine(125-i)

Radio labelled antigen is mixed with known

amount of antibody for the antigen and they

bind.

Sample serum from a patient containing an unknown of that same

antigen is added. This causes the unlabelled antigen(cold) from the serum to compete with the radio labelled antigen(hot) for antibody

binding site.

As the concentration of the cold antigen increases ,more of it

binds to the antibody ,displacing the radio labelled variant and

reduces the ratio of the antibody bound radio labelled antigen to

free radio labelled antigen.

The bound antigens are then seperated from the unbound

and the radio activity of the free antigen remaining in the

supernatant is measured using a gamma counter.

MANAGEMENTGOALS OF THERAPY

Releive the signs and symptoms of a disease

Decrease morbidity and mortality associated with

the infection.

To prevent the clinical attack of malaria

(prophylactic)

To treat the clinical attack of malaria (clinical

curative)

To completely eradicate the parasite from the

patients body (radical curative).

To cut down human to mosquito transmission

(gametocidal).

NON PHARMACOLOGICAL

Fluid therapy

Blood transfusion

Iron rich food

PH

AR

MA

CO

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GIC

AL

Dose: 1gm stat followed by 500 mg after 6 hours and 500 mg daily for next 2 days

C/I:pregnancy,liver damage,severe GI,hematologicaldiseases,eye impairment.

S/E:loss of hearing ,rashes, photo allergy,mentaldisturbances,myopathy …etc.,

CHLOROQUINE

MOA

Drug taken

up in the

erythrocyte

Concentrates in

the acidic

vacuoles of the

parasiteParasite digests the host haemoglobin

Transports it

into their

acidic food

vacuole

Toxic product

HAEM

HAEM HAEMOZOIN

(non-toxic)

HAEM POLYMERASE

CHLOROQUINE

Also inhibits

digestion of HB

Thus disrupts

parasites amino

acid supply

ATOVAQUONE

DOSE:250 mg

MOA: inhibits ETC leading to collapse of mitochondrial membrane .

C/I:Hypersensitivity.

S/E:insomnia, rash, weakness,abdominalpain.

MEFLOQUINE

Dose:15-25mg /kg

MOA: Same as that of chloroquine.

C/I: hypersensitivity

S/E: psychological changes (depression , confusion ,anxiety ,hallucination)

INT: quinidine and quinine, beta blocker, ty phoid vaccine and sodium valproate.

QUININE SULPHATE

Dose:15 mg daily for 14 days.

MOA: inhibits haem polymerase

C/I: patient is suffering from systemic disease

S/E:abdominal cramp ,epigastric distress ,anaemia, cyanosis and leukocytosis.

ARTESUNATEDose: parenteral 120 mg on 1st day followed by 60 mg daily for next 4 days.Oral 100 mg twice on 1st day followed by 50 mg twice daily for next 4 days.

MOA: Interacts with haem and generates free radicals that binds with membrane protein and damages.

S/E: Reticulocytopenia,bradycardia ,elevation of serum transaminases

INT:antimalarial action potentiated by oxidant drugs.

PYRIMETHAMINE

DOSE:25 mg

MOA: inhibits the conversion of dihydrofolicacid to tetrahyrofolic by blockade of dihydrofolate reductase

C/I:Hypersensitivity,anaemia,renal dysfunction,breastfeeding.

S/E:Anorexia,maliase,seizures,leucopenia,thrombocytopenia.

TREA

TMEN

T AL

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RITH

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GUIDELINES

TREATMENT OF UNCOMPLICATED

PLASMODIUM FALCIPARUM MALARIA

Artemisinin combination therapy (ACT) is the

drug of choice for all confirmed cases of

uncomplicated PF. This should be combined with

primaquine (PQ) (0.75 mg/kg body weight or 45

mg) on day-2. There are several ACTs

TREATMENT OF UNCOMPLICATED PLASMODIUM VIVAX MALARIA

Chloroquine is the drug of choice of Plasmodium vivax (PV) cases. It is given at a dose of 10 mg/kg (600 mg) on day-1 and day-2 and 300 mg on day-3.

Primaquine at a dose of 0.25 mg/kg (15 mg/day) for 14 days is to be added to prevent relapse. Primaquine is contraindicated in G6PD deficiency cases, infants and pregnant women.

TREATMENT OF SEVERE PLASMODIUM FALCIPARUM MALARIA

Artesunate: It is the drug of choice. It should be given in a dose of 2.4 mg/kg IV on admission (0 hour), then at 12 hours and 24 hours and then once daily till the patient takes orally or for 7 days. Then, they should get full course of ACT for 3 days

Quinine: Alternative to AS. It should be given at a dose of 20 mg /kg of body weight in 5% dextrose/ dextrose saline, over 4 hours. It is followed by 10 mg/kg of body weight 8 hourly infusions which should be started 8 hours after the 1st loading dose

TREATMENT OF SEVERE PLASMODIUM VIVAX MALARIA OR MIXED MALARIAL INFECTION

It should be treated as severe PF malaria cases.

TREATMENT OF SEVERE PLASMODIUM FALCIPARUM MALARIA CASES IN PREGNANCY

First trimester: Parenteral quinine is the drug of choice. If it is not available, parenteral artemisininderivatives can be given to save the life of the mother

Second trimester and third trimester: Parenteral artemisinin derivatives—AS is the drug of choice.

CHEMOPROPHYLAXIS

Short-term Prophylaxis (< 6 Weeks)

Doxycycline: 100 mg/day (1.5 mg/kg of bodyweight per day) to be started 2 days before andcontinued 4 weeks after leaving a malarias area.

Long-term Prophylaxis (> 6 Weeks)

Mefloquine: 250 mg weekly (5 mg/kg of bodyweight/week) to be started 2 weeks before goingto the affected area and continued for 4 weeksafter leaving the affected area.

COMPLICATIONS

Cerebral malaria

Destruction of blood cells(hemolytic anemia)

Kidney failure

Hypoglycaemia

Fluid ,electrolyte and acid –base disturbance

Circulatory collapse

Hyperpyrexia

Acidosis

Pulmonary edema

Rupture of the spleen

PREVENTION

Use mosquito repellants.

Sleep under mosquito nets – especially

effective if they have been treated with

insecticides

Use window screens

•Spray insecticides on your home’s

walls.

•Wear insect repellant and long sleeve

clothing when outdoors at night.

•Eliminate places around your home

where mosquitoes breed.

REFERENCES

Guidelines for the Treatment of Malaria 2010 (2nd edition). World Health Organization, 20, Avenue Appia-CH-1211 Geneva 27.

Guidelines for Diagnosis and Treatment of Malaria in India 2011 (2nd edition). Government of India, National Institute of Malaria Research, New Delhi.

Handbook of pharmacotherapy 7th edition by Joseph T Dipiro

Drug today

Essentials of medical pharmacology 7th edition KD Tripathi