Pharmacotherapy of Malaria

PST 06106

Basic Pharmacotherapy

Session 3: Pharmacotherapy of Malaria

Learning Objectives

By the end of this session students are expected to be able to:

Define malaria

Explain pathophysiology of malaria

Explain the clinical presentation of malaria

Outline diagnosis of malaria

Describe pharmacological treatment of malaria

Describe monitoring malaria therapy

Activity: Buzzing

What is the disease status of a patient with malaria?

Definition of Malaria

Uncomplicated malaria

: defined as symptomatic malaria without signs of severity or evidence (clinical or laboratory) of vital organ dysfunction.

It has the following features; fever, headache, joint pains, malaise, vomiting, diarrhoea, body ache, body weakness, poor appetite, pallor, enlarged spleen

Severe malaria:

In a patient with P. falciparum asexual

parasitemia

and no other obvious cause of symptoms the presence of one or more of features listed below classify the patient as suffering from severe malaria

It has the following features; prostration/extreme weakness, impaired consciousness, change of behaviour, convulsions, respiratory distress (due to lactic acidosis and/or pulmonary oedema), bleeding tendency, jaundice, circulatory collapse, vomiting everything, inability to drink or breast feed

Pathophysiology of Malaria

The

Plasmodium species that infect humans are

P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi

(rarely).

The

basic elements of the life cycle are the same for all Plasmodium

sp

Transmission begins when a female Anopheles mosquito feeds on a person with malaria and ingests blood containing gametocytes.

During the following 1 to 2

wk

, gametocytes inside the mosquito reproduce sexually and produce infective

sporozoites

.

When

the mosquito feeds on another human,

sporozoites

are inoculated and quickly reach the liver and infect hepatocytes.

Pathophysiology of Malaria

cont

….

The parasites mature into tissue

schizonts

within hepatocytes. Each

schizont

produces 10,000 to 30,000

merozoites

, which are released into the bloodstream 1 to 3

wk

later when the hepatocyte ruptures.

Each

merozoite

can invade an RBC and there transform into a

trophozoite

Trophozoites

grow, and most develop into erythrocyte

schizonts

;

schizonts

produce further

merozoites

, which 48 to 72 h later rupture the RBC and are released in plasma.

Pathophysiology

of Malaria

cont.….

These

merozoites

then rapidly invade new RBCs, repeating the cycle

Some

trophozoites

develop into gametocytes, which are ingested by an

Anopheles

mosquito

They undergo sexual union in the gut of the mosquito, develop into oocysts, and release infective

sporozoites

, which migrate to the salivary glands

Plasmodium Life Cycle

Clinical Presentation Of Malaria

Signs and symptoms of uncomplicated Malaria

Fever

Headache

Malaise

Joint pains

Vomiting /diarrhoea

Body ache

Poor appetite

Body weakness

Pallor

Enlarged spleen

Signs

and symptoms of Severe Malaria

Extreme

weakness

Impaired consciousness

Change of behaviour ( hallucinations, delusions, agitation, and acute state of confusion)

Respiratory distress

Bleeding tendency

Jaundice

Circulatory collapse/ shock

Vomiting everything

Inability to drink or

breastfeed

Diagnosis of Malaria

Parasite-based diagnosis is recommended for all patients presenting with signs and symptoms of malaria.

The recommended investigations are: malaria microscopy and malaria rapid diagnostic tests (

mRDTs

)

In severe malaria, blood slide (BS) is a recommended malaria test as it quantifies parasitemia.

Activity: Small Group Discussion

What is pharmacological treatment of

malaria

?

Pharmacological Treatment of Malaria

Management OF Uncomplicated

M

alaria

Drug

of choice for treatment of uncomplicated malaria is Artemether-Lumefantrine (AL), which is a fixed formulation of artemether 20mg and lumefantrine 120mg or dispersible tablets for paediatric

use.

Dosage regimen of ALU

Pharmacological Treatment of Malaria Cont.…..

Use of

Artemether-lumefantrine

(

ALu

) in Pregnancy

Presently, Artemisinin compounds cannot be recommended for treatment of malaria in the first trimester of pregnancy.

In the first trimester of pregnancy quinine should be used as first line treatment.

After the first trimester

ALu

tablets is first line medicine.

Use of

Artemether-lumefantrine

(

ALu

) in Lactation

Due to the long elimination half-life of

Lumefantrine

(up to 10 days), it is not recommended in mothers breast-feeding children below 5kgs.

In this case quinine should be used

.

Pharmacological Treatment of Malaria Cont.…..

Management of Severe Malaria

Parenteral

artesunate

bwt

Major Anti Malarial Drugs

Monitoring Of Malaria Therapy

It is important to monitor Malaria therapy in order to evaluate if it is effective

Patients can be monitored clinically and/or by using laboratory test to confirm for absence/presence of malaria parasite in their blood

A follow-up period after the completion of the Malaria therapy varies according to the drugs used.

Follow-up periods longer than 14 days are appropriate for

amodiaquine

, chloroquine and SP which is 28 days

For

lumefantrine+artemether

is 42 days,

For

mefloquine

is 63 days

Monitoring Of Malaria Therapy

Cont

…

This allows drug levels in the blood to fall below the minimum therapeutic threshold.

Any recrudescence of parasites before this threshold is reached would be due to drug resistance

Recrudescence after this threshold is reached is not necessarily related to resistance (even sensitive parasites could recrudesce if blood drug levels are

subtherapeutic

).

Shorter follow-up (i.e. <14 days) will underestimate overall treatment failure rates

It is also important for patient to report any adverse reaction of the drugs that may occurs during Malaria therapy.

Key Points

P

. falciparum

causes microvascular obstruction and tissue ischemia, particularly in the brain, kidneys, lungs, and GI tract of nonimmune infants and adults; patients may die within days of their initial symptoms.

P.

vivax

, P.

ovale

, and

P.

malariae

typically do not compromise vital organs; mortality is rare.

Clinical

maanifestations

include recurrent fever and rigor, headache, myalgia, and nausea; hemolytic anemia and splenomegaly are common.

Treatment with antimalarial drugs is based on the species (if known) and drug resistance patterns in the area in which infection was acquired

Artemisinin

-based combination therapy (

eg

,

artemether

/lumefantrine) is the most rapidly active therapy and is available worldwide

Evaluation

What

is the disease status of a patient with Malaria?

What is the pathophysiology of malaria?

What is the diagnosis of malaria?

What parameters can be used to monitor malaria therapy

References

Wells BG,

DiPiro

J,

Schwinghammer

T (2013), Pharmacotherapy Handbook (6th Ed). New York, NY: McGraw-Hill.

DiPiro

JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008): Pharmacotherapy: A Pathophysiologic Approach (7th

ed

): New York, NY: McGraw-Hill.

Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011) Principles & Practice Study Guide: A Case-Based Care Plan Approach: New York, NY: McGraw-Hill.

Schwinghammer

TL, Koehler JM (2009) Pharmacotherapy Casebook: A Patient-Focused Approach (7th

ed

): New York, NY: McGraw-Hill.

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