MALARIA THERAPY

Professor A.O. Isah

Consultant Physician/Clinical
Pharmacologist
UNIBEN/UBTH
Benin City
 MALARIA

‘IF WE TAKE AS OUR STANDARD OF

IMPORTANCE, THE GREATEST HARM
TO THE GREATEST NUMBER, THEN
THERE IS NO QUESTION THAT MALARIA
IS THE MOST IMPORTANT OF ALL
INFECTIOUS DISEASES’

SIR MACFARLANE
BURNET
 MALARIA
Historical perspectives

 Known cause of fevers since ancient times in China,

India, Mesopotamia
 Earliest records – Hippocrates in 5th Century B.C
 Associated with marshy areas.
 Refered to as Paludial - [Palus – Latin for marshy]
 Association with atmospheric poisons – mal ` aria
[bad air]
 Discovery of Parasite – Late 18th Century
- Laveran, Mason, McCallum, Ross
 MALARIA
Definition/Aetiology

 A protozoal disease transmitted by female

Anopheles mosquito.

 Vectors in Nigeria
 Anopheles gambiae (main vector)

 Anopheles funestus

 Anopheles arabiensis

 Anopheles melas (found in coastal areas)

 MALARIA
Causative organism

 P.falciparum – predominantly
 P. malariae ]
]
 P.ovale ]
 P.vivax - Not found in indigenous Nigerians

Zoonotic - occasionally infects man

 P. cynomolgi, P. knowlesi, P. semiovale
 MALARIA

 A hidden global scourge with Africa at its

epicentre

 Associated with suffering of the population

 Thwarts children cognitive development and

education
 MALARIA
Current global malaria situation

 About 100 countries or territories considered

malarious

 In Africa, Asia,Oceania, Central and South

America and in certain Carribean Islands

 ~ 50% in Africa South of the Sahara

 MALARIA
Current global malaria situation

 2 – 3 billion persons live in these areas

 ~ 300 - 500 million cases occur annually

 1.1 – 2.7 million deaths/year ; ~ 1 million

children in Africa South of Sahara

 Imported and Airport Malaria

 MALARIA
Current malaria situation - Nigeria

 Over 100 million people at risk of malaria

every year
 Major cause of morbidity and mortality
 Most common cause of outpatient visits
 50% of population experience at least one

episode each year

 Under five children experience up to 2 – 4

attacks of malaria each year

 Ranks among the five common causes of death
 MALARIA
 Adverse influence on economy

 Limits ability to make a living and care for family

 Malaria keeps poor people poor

 Marked correlation between malaria and poverty

 Average GDP in malarious areas 5x less than non-

malarious areas

 US$ 12billion (~ N1560 billion) lost every year in Africa

 MALARIA
Current malaria situation - Nigeria

 Annual economic loss ~ N 132 billion

 Cost of treatment

 Transport to source of treatment

 School absenteeism

 Loss of man – hours

 Other indirect costs

 Thus heavy cost on country’s economy, its rate

of economic growth and level of economic
development
 MALARIA
CLINICAL FEATURES
 
Variable and depends upon:
 
• Level of immunity of host
 
• Level of parasitaemia (& type)
 
• Occurrence of complications
 MALARIA
Classification

 Uncomplicated
 No life threatening symptoms

 Severe or Complicated
 A medical emergency
 MALARIA CHEMOTHERAPY
Clinical features

 The first symptoms of malaria are nonspecific

and similar to the symptoms of a minor
systemic viral illness
 MALARIA
Clinical features of uncomplicated malaria

 Fever
 Headache
 Muscle pains
 Joint aches
 Chills & rigors
 Malaise
 Loss of appetite
 Abdominal pain
 Vomiting
Severe malaria
Clinical manifestation or Laboratory findings

Cerebral Malaria Respiratory distress

Hyperpyrexia Pulmonary oedema
Persistent vomiting Abnormal bleeding
Severe Anaemia
Jaundice
Impaired consciousness
Haemoglobinuria
Multiple convulsions
Hyperparasitaemia
Circulatory collapse
[Shock] Hypoglycaemia
Prostration Renal failure
 MALARIA
Differentials
 Acute viral illness
 Meningitis
 Encephalopathy
 Diabetes Mellitus
 Septicaemia
 Epilepsy
 etc
 Investigations

Blood smear (thick and thin films) for MP

Haematocrit/ Hb
FBC
Blood sugar
Urinalysis
E/U
Lumbar Puncture
Blood culture
Chest Xray
Blood gases
 Laboratory tests
 Microscopy
 Giemsa stain (thick and thin films)

 Leishman stain (thin film)

 Quantitative Buffy Coat

 Benzothiocarboxypurine (BPC) method

 Laboratory tests
 Rapid diagnostic tests (antigen detection based tests)
 Parasight F

 Optimal T

 Serological tests
 Indirect fluorescent Antibody test (IFAT)

 Indirect Haemagglutination (IHA) test

 Immunoprecipitation Technique (Double gel

diffusion tests

 Enzyme Linked Immunosorbent Assay (ELISA)

technique
 Investigations

Blood smear (thick and thin films) for MP

Haematocrit/ Hb
FBC
Blood sugar
Urinalysis
E/U
Lumbar Puncture
Blood culture
Chest Xray
Blood gases
 MALARIA CHEMOTHERAPY
National Antimalarial Policy

 The National Antimalarial policy describes our goal

with respect to the treatment of malaria and the strategy
by which the goal is to be achieved

 The primary goal of treatment in malaria is to cure the

patient of the infection and thereby reduce morbidity
and mortality.

 A second purpose is to encourage rational drug use to

prevent or delay the development of antimalarial drug
resistance
 MALARIA CHEMOTHERAPY
Old drugs

 Extracts of Cinchona tree [Quinine ] in the 13th Century

– Used to treat the Countess of Cinchon, wife of Viceroy of Peru [1630]

 Mepacrine

 4 – Aminoquinolines - Chloroquine
 MALARIA CHEMOTHERAPY
1950s

 WHO-led Global eradication programme –aimed at

eliminating disease by vector control with DDT and
through treatment with chloroquine

 Africa - eradication considered impractical because of

high level of transmission and the lack of infrastructure.
 MALARIA CHEMOTHERAPY

 Abandonment due to resistance and safety concerns to

insecticides.

 WHO settled for control programmes

 Emphasis on prompt diagnosis and treatment with

chloroquine (cheap and available) and other control
measures

 Development of drug resistance

 Prospects for vaccine

 MALARIA RESURGENCE

 Development of drug resistance

 Human migration – war/conflict

 Weak Public Health Systems – poverty, war, political

instability

 Changing demographics and land use

 MALARIA RESURGENCE

Development of drug resistance

 Chloroquine
 introduced in the ’50s

 resistance spreading from SE Asia and S America

late ’50s/’60s, reaching Africa in late 1970s

 Sulphadoxine/Pyrimethamine (Fansidar)
 introduced in the 70s (Africa in the 90s)

 resistance observed within 5 years

 MALARIA RESURGENCE

Development of drug resistance

 Increased morbidity and mortality

WHO recommendations

 WHO has now lowered the resistance - threshold

recommended for treatment policy change from 25%
to 10% as assessed by standard WHO protocols in
children under 5 years of age

 Effective treatment should be adopted when the

proportion of treatment failures to the old treatment
reaches 10%
 MALARIA CHEMOTHERAPY

 WHO on the advise of international experts

recommends the introduction of combinations of drugs
to replace single drugs (monotherapy) in the treatment
of malaria…

 WHO recommends in particular, the use of drug

combinations containing artemisinin compounds –
artemisinin-based combination therapy - ACT for
short. WHO statement February 2002.
 MALARIA CHEMOTHERAPY
National Antimalarial Policy - Preparation
 Information available on malaria parasite drug
resistance
 Consider current drugs and their roles in malaria
management
 Drugs selected using the following criteria:
 Efficacy and proven effectiveness against malaria

species
 Safety

 Simplicity of dosage

 Availability [registration] in the country

 Cost
MALARIA CHEMOTHERAPY

ESSENTIAL ANTIMALARIAL DRUGS

 Are those drugs that meet the needs of

appropriate antimalarial treatment in the vast
majority of the people. They should therefore
be available at all times, in adequate amounts
and appropriate dosage forms and should be
affordable to the people
LIST OF ESSENTIAL ANTIMALARIAL DRUGS

 Current drugs for uncomplicated malaria

 Current drugs for severe malaria

 Other drugs for multi-resistant malaria

 Older drugs for treatment of uncomplicated malaria

 Adjunctive drugs
MALARIA CHEMOTHERAPY

ANTIMALARIAL DRUGS
 First line drug – recommended drug of primary
intention for treating uncomplicated malaria in
the country as determined by the antimalarial
drug policy

 Second line drug - recommended drug for

treatment of uncomplicated malaria where there
is clinical failure or intolerance to the first line
drug
 MALARIA CHEMOTHERAPY
Uncomplicated Malaria

 Current drugs for treatment of uncomplicated malaria

are Artemisinin based combination therapies

 The combination takes advantage of :

 the rapid schizonticidal action of artemisinins and

 the long duration of action of the partner compound

to effect rapid cure with low level recrudescence

 MALARIA CHEMOTHERAPY
Uncomplicated Malaria

 The objective of treating uncomplicated

malaria is to cure the infection.

 Cure of the infection means eradication

from the body of the infection that caused the
illness

prevent progression to severe disease and

prevent additional morbidity associated with

treatment failure
 MALARIA CHEMOTHERAPY
Uncomplicated Malaria

A secondary but equally important objective of

treatment is to prevent the emergence and spread
of resistance to antimalarials.

The public health goal of treatment is to reduce

transmission of the infection to others, i.e. to
reduce the infectious reservoir
 Current drugs for uncomplicated
malaria
The most widely advocated combinations are those in
which the artemisinin compounds are combined with a
longer acting antimalarial. These include:

 Artemether (20mg)+ Lumefantrine (120mg) - Tablet

 Artesunate (4mg/kg)+Amodiaquine (10mg/kg) – Tablet


 Artesunate(4mg/kg)+Mefloquine (15– 25mg/kg) - Tablet
MALARIA CHEMOTHERAPY
ACT

 Artemether + Lumefantrine
 Artesunate + Amodiaquine
 Artesunate + Mefloquine
 Artesunate + SP
 Artemisinin – based Combination Therapy
ACT
Artemeter (20mg) + Lumefantrine (120mg)

Brand Name Components Cost (N)

 Coartem Artemether 1,300

+
 Lonart Lumefantrine 850
Tablet

Suppositories
 Artemisinin –based Combination Therapy
ACT
Artesunate + Amodiaquine

Brand Name Manufact. Components Cost (N)

 Larimal Ipca 50mg + 153mg 900

 Quinsunate 50mg + 153mg 800
 Diasunate Emzor 100mg + 306mg 800
MalACT M&B 100mg + 306mg 700
Dart Swipha 200mg + 600mg 800
Gsunate Kit Greenlife 200mg + 600mg
 Artemisinin –based Combination Therapy
ACT

Brand Name Manufact. Components Cost (N)

 Co-Arinate Dafra Artesunate 850

(Reals) (50mg)
+
Sulpha
methopyrazine/
Pyrimethamine
(25mg)
 Artemisinin –based Combination Therapy
ACT

Brand Name Manufact. Components Cost (N)

 Farenax Swipha Artesunate 900

(50mg)
+
SP
Therapeutic efficacy of anti-malarial drugs in Nigeria

No Zone CQ SP ART/ ARS/

(%) (%) LUM AMQ
(%)
(%)
1. SE 3.7 14.9 100 100
2 SS 9.1 8.5 87 82.5
3 NC 53.2 82.7 100 96
4 NW 77.3 94.2 100 100
5 SW 40.9 75.6 100 100
6 NE 50.8 64.8 100 100
ACT challenges
 Prohibitive cost (from < $ 1.0 to > $ 6.0 per course of
treatment)

 Pill burden

 Tolerability poor

 Adverse Effects

 Reluctance of health care providers to prescribe

 Summary of CEM Study (Bassi et al)

• Most common Adverse Events (AEs) observed in

the Cohort are
General body weakness - 38/36 % (AA/AL)
dizziness - 16.2/1.4%
(AA/AL
Loss of appetite - 9.1/3.5 %
( AA/AL)
Vomiting - 7/ - %
(AA/AL),
Abdominal Pain - 6.1/1.0% (AA/AL)

• Mean Duration of illness (events) is 3days.

21
 Current medicines for
severe malaria
 Quinine injection

 Artemether injection

 Artesunate injection

 Artesunate suppositories

Once a patient with severe malaria can take orally

following initial administration of parenteral antimalarial,
change to the first line antimalarial and give a full course
 Older medicines for treatment of
uncomplicated malaria

 Sulfadoxine/pyrimethamine – Not
recommended for treatment of malaria.
Reserved for intermittent preventive
treatment (IPT) in pregnancy

 Chloroquine – Inadequate efficacy and

therefore no longer recommended
 Some brand names of the
sulphadoxine-pyrimethamine
combination products
 Fansidar
 Metakalfen
 Amalar
 Laridox
 Maloxine
 Maldox
 Malareich
 MALARIA CHEMOTHERAPY
Severe Malaria
 Drug of Choice – Quinine ;
 Dosage [initial parenteral administration]

IV Quinine
 Loading dose – 20mg/kg quinine dihydrochloride
[salt] diluted in 10ml/kg of 5% dextrose saline to run
over 4 hours [Avoid if previous administration]
 Then 8hours after start of loading dose – 10mg/kg
salt to run over 4 hours every 8 hours until patient
can take orally
[reduce to 5 - 7mg/kg if IV required for > 48hours]
 When patient can take orally:

 Change to quinine tablets 10 mg/kg 8 hourly to

complete a total of 7 days treatment
OR
 Give a full dose of artemether-lumefantrine
 MALARIA CHEMOTHERAPY
Severe Malaria

IM quinine –
 Dose as for IV.
 Dilute to 60 – 100mg/ml.
 Administer in divided sites
 Ensure sterile procedure
 Administer to anterior thigh & not buttocks !
 MALARIA CHEMOTHERAPY
Severe Malaria
Artemisinin & derivatives – Alternative to Quinine

Artesunate
Loading dose - IV bolus 2.4mg/kg
Then 1.2mg/kg after 12 hours
Then 1.2 mg/kg daily - x 6 days Change
daily dose to oral if patient able to swallow
Artemether
Loading dose – IM 3.2mg/kg
Then 1.6 mg/kg daily - x 6 days Change
daily dose to oral if patient able to swallow
 MALARIA CHEMOTHERAPY
Severe Malaria
 Supportive therapy
 Analgesic/antipyretic

 Quality Care
 Monitor Vital Signs

 Monitor Fluid Input and Output

 Monitoring Level of Unconscious

 Drug Chart
 Laboratory monitoring
 Parasitaemia

 Blood sugar

 Haematocrit/Haemoglobin
 MALARIA CHEMOTHERAPY
Severe Malaria

 Assessment of recovery

 Health Education and Prevention

 MALARIA CHEMOTHERAPY
Prophylaxis
High risk groups
 Pregnancy

 Sickle cell anaemia

Proguanil 200mg daily

 Non-immune visitors
Start 1 week before arrival & 4 weeks after
departure
Mefloquine 250mg weekly
Atovaquone/proguanil
 MALARIA CHEMOTHERAPY
Prophylaxis
 Pregnancy

 Intermittent Preventive Therapy (IPT) – Full dose

of sulphadoxine/pyrimethamine during the 2nd and
3rd trimesters. Ist dose  16 weeks of pregnancy.
Last dose not later than one month before the
expected date of delivery
 MALARIA CHEMOTHERAPY
Treatment failures
 Failure to achieve the desired therapeutic response
following administration of an antimalarial drug

 It should be considered if fever or other symptoms

of malaria persists up to the third day after starting
treatment in adequate recommended dosage
regimen
 DRUG RESISTANCE
[in malaria]
Ability of a parasite strain to survive and /or
multiply despite the administration and
absorption of a drug given in doses equal to
or higher than those usually recommended
but within the limits of tolerance of the
subject

WHO
DRUG RESISTANCE
Monitoring of drug resistance

Primary objective of monitoring drug resistance is

to evaluate the efficacy of the recommended
treatment options for malaria at the local level, with
particular emphasis on P. falciparum.

Methods for Monitoring of drug resistance

 Therapeutic efficacy of antimalarial drugs [replaced
standard in vivo test]
 In vitro susceptibility testing of parasites
 Study of genetic markers of resistance
DRUG RESISTANCE
Monitoring of therapeutic efficacy
 Set up by WHO in 1994
 A new system for monitoring the therapeutic
efficacy of antimalarial drugs used for the
treatment of uncomplicated falciparum
malaria
 Based on clinical evaluation of selected malaria
patients, using a limited number of follow-up
examinations
DRUG RESISTANCE
Monitoring of therapeutic efficacy
Basic tests consists of obtaining the following:
Day 0  Provide supervised
 Recording essential treatment
patient information Days 3, 7, 14
 Clinical assessment  Repeat Clinical and
 Body temperature parasitological
 Body weight examinations
 Parasitaemia
 Haemoglobin levels
DRUG RESISTANCE
Monitoring of therapeutic efficacy
Basic tests consists of obtaining the following:
Day 0
 Recording essential  Provide supervised
patient information treatment
 Clinical assessment Days 3, 7, 14
 Body temperature  Repeat Clinical and
 Body weight parasitological
 Parasitaemia examinations
 Haemoglobin levels
 DRUG RESISTANCE
Monitoring of therapeutic efficacy
Classification
 Clinical and Parasitological criteria used to
classify the response to treatment as
 Adequate Clinical response

 Early treatment failure [from days 1 to 3]

 Late treatment failure [ from days 4 to 14]

THANKS FOR LISTENING