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Title: Introduction 1


1
Introduction 1
Malaria
  • Welcome to the malaria module!
  • Malaria is a major public health problem in warm
    climates especially in developing countries.
  • It is a leading cause of disease and death among
    children under five years, pregnant women and
    non-immune travellers/immigrants.

Children under 5 are the major at risk group in
malarious regions. Inset An Anopheles mosquito
taking a blood meal Sources http//www.ifnc.org/p
ictures.html http//phil.cdc.gov/phil/quicksearch
.asp
For more information about the authors and
reviewers of this module, click here
2
How to use this module
  • This self-directed learning (SDL) module has been
    designed for medical and other health care
    students
  • We suggest that start with the learning
    objectives and try to keep these in mind as you
    go through the module slide by slide, in order
    and at your own pace.
  • Print-out the malaria SDL answer sheet. Write
    your answers to the questions on the mark sheet
    as best you can before looking at the answers.
  • Repeat the module until you have achieved a mark
    of gt 22/27 (gt80).
  • You should research any issues that you are
    unsure about. Look in your textbooks, access the
    on-line resources indicated at the end of the
    module and discuss with your peers and teachers.
  • Finally, enjoy your learning! We hope that this
    module will be enjoyable to study and complement
    your learning about malaria from other sources.

3
Introduction 2
Learning Outcomes
  • By the end of the module, you would be expected
    to be able to describe
  • How P. falciparum malaria is a major killer of
    people in warm climates and that children lt5
    years, pregnant women and non-immune
    visitors/immigrants are at greatest risk
  • The 4 main species of malaria, their geographical
    distribution and the major stages of the life
    cycle
  • How malaria is transmitted by the female
    anopheles mosquito and how levels of endemicity
    vary according to climate and mosquito ecology
  • How parasite and host factors determine disease
    severity
  • The clinical features of simple, uncomplicated
    disease and 8 important severe manifestations of
    malaria
  • How malaria is diagnosed by blood film
    examination, antigen detection and molecular
    methods
  • The role of chloroquine, quinine, artemesinin and
    other drugs in treatment
  • How malaria can be prevented by reducing
    man-mosquito contact, chemoprophylaxis,
    intermittent presumptive treatment and what
    approaches are being taken in vaccine development

4
What is malaria ?
Malaria is a disease caused by single-celled
protozoan parasites of the genus Plasmodium. The
4 species that commonly infect man are
Species Major features
P. falciparum The most important species as it is responsible for 50 of all malaria cases worldwide and nearly all morbidity and mortality from severe malaria Found in the tropics sub-tropics
P. vivax The malaria parasite with the widest geographical distribution Seen in tropical and sub-tropical areas but rare in Africa Estimated to cause 43 of all malaria cases in the world
P. ovale This species is relatively rarely encountered Primarily seen in tropical Africa, especially, the west coast, but has been reported in South America and Asia
P. malariae Responsible for only 7 of malaria cases Occurs mainly in sub-tropical climates
5
The burden of malaria
  • This can be divided into
  • The direct health burden morbidity and
    mortality
  • The indirect burden impaired human and
    economic development
  • Click on the boxes to find out more

Direct burden
Indirect burden
6
Geographical Distribution of Malaria
Although previously widespread, today malaria is
confined mainly to Africa, Asia and Latin
America. About 40 of the worlds population is
at risk of malaria. It is endemic in 91
countries, with small pockets of transmission
occurring in a further 8 countries.
Malaria is transmitted by the female anopheles
mosquito. Factors which affect mosquito ecology,
such as temperature and humidity, are key
determinants of malaria transmission. Mosquitoes
breed in hot, humid areas and below altitudes of
2000 meters. Development of the malaria parasite
occurs optimally between 25-30oC and stops below
16oC. Indigenous malaria has been recorded as far
as 64oN and 32oS. Malaria has actually increased
in sub-Saharan Africa in recent years. The major
factor has been the spread of drug-resistant
parasites. Other important factors include the
persistence of poverty, HIV/AIDS, mosquito
resistance to insecticides, weak health services,
conflict and population migration.
7
Endemicity and immunity to malaria
Endemicity refers to the level of transmission
of malaria. Malaria is endemic in an area or
community when there is a constant incidence of
cases over successive years. People gradually
develop immunity to malaria if continuously
exposed. Malaria endemicity can be classified as
Hypoendemic Little transmission malaria has
little effect on the population.
  • Malaria epidemics occur when transmission
    increases amongst susceptible populations.
    Epidemics do not occur in holoendemic areas
    because of the high level of immunity.

8
End of Section 1
  • Well done!
  • You have come to the end of the first section.

,
  • We suggest that you answer Question 1 to assess
    your learning so far. Please remember to write
    your answers on the mark sheet before looking at
    the correct answers!

Click to Reveal Answers
9
Question 1Write T or F on the answer sheet.
When you have completed all 5 questions, click on
the box and mark your answers.
Click for the correct answer
  • P. ovale occurs mainly in West Africa
  • P. falciparum is the most important species of
    malaria
  • The largest burden of malaria occurs in South
    East Asia
  • Malaria epidemics are likely to occur in a
    holoendemic area
  • e) Environmental factors which affect mosquito
    breeding are closely related to the intensity of
    malaria transmission

a
b
c
d
e
10
How is malaria transmitted?
  • Malaria parasites are transmitted from one person
    to another by the bite of a female anopheles
    mosquito.
  • The female mosquito bites during dusk and dawn
    and needs a blood meal to be able to produce
    eggs.
  • Male mosquitoes do not transmit malaria as they
    feed on nectar and plant juices and not blood.
  • There are about 380 species of anopheles mosquito
    but only about 60 are able to transmit malaria.
  • Like all mosquitoes, anopheles breed in water -
    hence accumulation of water favours the spread of
    the disease.
  • The flight range of Anopheles is only about 2-3
    km but they may travel further if blown by the
    wind or carried in ships or aeroplanes.

Female Anopheles mosquito taking a blood
meal Sourcehttp//phil.cdc.gov/phil/quicksearch.
asp
11
How does infection develop ?
  • Plasmodium infects the human and insect host
    alternatively and several phases of the parasite
    occur. The duration of each phase varies
    according to the species and is as follows for P.
    falciparum

Mosquito phase During feeding, the mosquito
injects anticoagulant saliva into the blood
stream. If the mosquito is infected, the saliva
contains primitive stages of malaria called
sporozoites.
Hepatic, tissue or pre-erythrocytic phase
Sporozoites immediately invade liver cells and
begin to develop. The infected hepatocyte
ruptures to release merozoites after about 5-7
days.
Erythrocytic phase Merozoites then invade red
blood cells. The red cells lyse and this causes
bouts of fever and other symptoms. This cycle
repeats about every 36 hours as merozoites invade
other red cells.
Then the cycle repeats
Sexual phase Sexual forms develop and are
ingested when another female anopheles mosquito
feeds. These develop into sporozoites in the gut
of the insect host and migrate to its salivary
glands.
The life cycle of the malaria parasite is shown
on the next slide
12
The Malaria Parasite Life Cycle
Click on the diagram to explore different areas
of the life cycle
Show Me
13
The Malaria Parasite Life Cycle
Back
14
The Malaria Parasite Life Cycle
1. Transmission Female anopheles mosquito bites
and releases sporozoites into the blood stream.
These circulate for about 30 mins and then invade
the liver.
15
The Malaria Parasite Life Cycle
2. Pre-erythrocytic phase Also called the
tissue or hepatic phase Takes place in
hepatocytes. The sporozoites mature into
schizonts which rupture to release merozoites.
Duration of this phase depends on the species.
In P. vivax and P. ovale, the schizont may also
differentiate into hypnozoites. These are dormant
forms of the parasite which may remain in the
liver for several months or years and cause
relapse in the human host.
16
The Malaria Parasite Life Cycle
3a. Asexual phase (Erythrocytic
schizogony) Merozoites invade red blood cells.
Here they grow and mature into trophozoites which
appear as ring forms. The trophozoites develop
into schizonts. The infected red blood cells then
rupture to release numerous merozoites from the
schizont to infect other red cells. Merozoite
release results in fever, chills, rigours and
other symptoms of malaria infection.
17
The Malaria Parasite Life Cycle
3b. Sexual phase Some merozoites differentiate
into male and female gametocytes, the forms of
Plasmodia infective to mosquitoes. These are
taken up by a mosquito during another blood meal.
These fuse to form an ookinette in the gut lumen
of the mosquito. The ookinette invades the
stomach wall to form the oocyst. This in turn
develops and releases sporozoites which migrate
to the salivary gland of the mosquito. This
mosquito then goes on to infect another human
host.
18
Severity of disease and host factors
  • In addition to parasite factors, several host
    factors determine the outcome of exposure to
    malaria
  • Naturally-acquired immunity. People who are
    constantly exposed to malaria gradually acquire
    immunity, firstly against clinical disease and
    later against parasite infection. Clinical
    manifestations of malaria are most severe in the
    non-immune. In holoendemic areas, these are
    children aged lt5 years and pregnant women
    (especially primagravidae). People of any age
    from areas that are free from malaria, or have
    limited malaria transmission, are at risk when
    they are exposed to malaria.
  • Red cell and haemoglobin variants. Well known
    examples of inherited factors that protect
    against malaria are Haemoglobin S carrier state,
    the thalassaemias and Glucose-6-phosphate
    dehydrogenase (G6PD) deficiency. Malaria provides
    the best known example whereby an environmental
    factor (malaria) has selected human genes because
    of their survival advantage.
  • Foetal haemoglobin (HbF) High levels of HbF
    occur in neonates, and in some people with
    inherited haemoglobin variants, protect against
    severe forms of P. falciparum malaria.
  • Duffy blood group P. vivax requires the Duffy
    blood receptor to enter red blood cells.
    Therefore, people who do not carry the Duffy
    blood group are resistant to this malaria
    species. This explains the rarity of P. vivax in
    Africa, as most Africans are Duffy blood group
    negative.

19
End of Section 2
  • Well done!
  • This is the end of the second section.
  • We suggest that you proceed to answer questions 2
    and 3 to assess your learning further. Do
    remember to write your answers on the mark sheet
    before looking at the right answer!

20
Question 2 Parasite factors and disease
severity. Study the table below. Write down on
your answer sheet 2 features of the biology of P.
falciparum which contribute to it being
responsible for nearly all severe malaria. Then
click on the box and mark your answers.
Click here for the answers
Duration of tissue phase (days) Incubation period (days) Number of merozoites / cell Red cells invaded
P. falciparum 5.5 7 8 - 11 40,000 cells of all ages
P. vivax 6-8 10 17 or up to 12 months 10,000 reticulocytes
P. ovale 9 10 17 or longer 15,000 reticulocytes
P. malariae 14-16 18 40 or longer 2,000 mature cells
Incubation period is the number of days from
exposure (injection of sporozoites) to the onset
of clinical symptoms.
21
Question 3 The following people are at risk of
severe malariaWrite T or F on the answer
sheet. When you have completed all 7 questions,
click on the box and mark your answers.
Click for the correct answer
a
  1. Pregnant women
  2. Neonates
  3. Immigrants from Europe
  4. A 20 year old man who has lived all of his life
    in Nigeria
  5. A 3 year old girl resident in an area holoendemic
    for malaria
  6. A 10 year old child with sickle cell disease
  7. A 3 year old boy with Duffy negative blood group

b
c
d
e
f
g
22
The clinical course of P. falciparum
Following a bite by an infected mosquito, many
people do not develop any signs of infection. If
infection does progress, the outcome is one of
three depending on the host and parasite factors
enumerated in the previous slides
Asymptomatic parasitaemia B. Acute, uncomplicated malaria C. Severe malaria
(clinical immunity) (mild malaria)
23
A. Asymptomatic parasitaemia
This is usually seen in older children and
adults who have acquired clinical immunity to
disease as a consequence of living in areas with
high malaria endemicity. There are malaria
parasites in the peripheral blood but no
symptoms. These individuals may be important
reservoirs for disease transmission. Some
individuals may even develop anti-parasite
immunity so that they do not develop
parasitaemia following infection.
24
B. Simple, uncomplicated malaria
This can occur at any age but it is more likely
to be seen in individuals with some degree of
immunity to malaria. The affected person, though
ill, does not manifest life-threatening disease.
Fever is the most constant symptom of malaria.
It may occur in paroxysms when lysis of red cells
releases merozoites resulting in fever, chills
and rigors (uncontrollable shivering).
Children with malaria waiting to be seen at a
malaria clinic in the south western part of
Nigeria. Identifying children with severe
malaria, and giving them prompt treatment, is a
major challenge when large numbers attend clinics.
25
The periodicity of malaria fever
  • Erythrocytic schizogony is the time taken for
    trophozoites to mature into merozoites before
    release when the cell ruptures.
  • It is shortest in P. falciparum (36 hours),
    intermediate in P. vivax and P. ovale (48 hours)
    and longest in P. malariae (76 hours).
  • Typical paroxysms thus occur every
  • 2nd day or more frequently in P. falciparum
    (sub-tertian malaria)
  • 3rd day in P. vivax and P. ovale (tertian
    malaria)
  • 4th day in P. malariae infections, (quartan
    malaria)

Note how the frequency of spikes of fever differ
according to the Plasmodium species. In practice,
spikes of fever in P. falciparum, occur
irregularly - probably because of the presence of
parasites at various stages of development.
26
Other features of simple, uncomplicated malaria
include
  • Vomiting
  • Diarrhoea more commonly seen in young children
    and, when vomiting also occurs, may be
    misdiagnosed as viral gastroenteritis
  • Convulsions commonly seen in young children.
    Malaria is the leading cause of convulsions with
    fever in African children.
  • Pallor resulting mainly from the lysis of red
    blood cells. Malaria also reduces the synthesis
    of red blood cells in the bone marrow.
  • Jaundice mainly due to haemolysis.
  • Malaria is a multisystem disease. Other common
    clinical features are
  • Anorexia
  • Cough
  • Headache
  • Malaise
  • Muscle aches
  • Splenomegaly
  • Tender hepatomegaly
  • These clinical features occur in mild malaria.
    However, the infection requires urgent diagnosis
    and management to prevent progression to severe
    disease.

27
C. Severe and complicated malaria
Nearly all severe disease and the estimated gt1
million deaths from malaria are due to P.
falciparum. Although severe malaria is both
preventable and treatable, it is frequently a
fatal disease. The following are 8 important
severe manifestations of malaria Click on each
severe manifestation for details
  1. Acute renal failure
  2. Pulmonary oedema
  3. Circulatory collapse, shock or algid malaria
  4. Blackwater fever
  1. Cerebral malaria
  2. Severe malaria anaemia
  3. Hypoglycaemia
  4. Metabolic acidosis

Note It is common for an individual patient to
have more than one severe manifestation of
malaria!
28
Summary of differences in the clinical features
of severe malaria in adults and children
Frequency of occurrence
Clinical Manifestation Children Adults
Similar in adults and children Prostration Circulatory collapse
More common in children Cerebral malaria Severe anaemia Multiple convulsions Metabolic acidosis Hypoglycaemia / -
More common in adults Jaundice Pulmonary oedema Haemoglobinuria Abnormal bleeding Renal failure / - / - / - / -
29
End of Section 3
  • You have made tremendous progress!
  • This is the end of the third section.
  • You should now be able to answer Question 4 to
    assess what you have learnt. You are to remember
    to write your answers on the mark sheet before
    looking at the right answer!

30
Question 4 Clinical malariaWrite T or F on
the answer sheet. When you have completed all 7
questions, click on the box and mark your
answers.
Click for the correct answer
  1. Asymptomatic parasitaemia signifies acquired
    immunity to malaria
  2. Symptoms typically occur during the hepatic phase
    of infection
  3. Young children with mild malaria require urgent
    assessment and treatment
  4. A single convulsion signifies severe disease
  5. The clinical signs of acidosis are rapid
    respirations with deep breathing
  6. Acute renal failure occurs in older children and
    adults
  7. A patient with malaria and dark urine is unlikely
    to be anaemic

a
b
c
d
e
f
g
31
Diagnosis
  • Malaria is a multisystem disease. It presents
    with a wide variety of non-specific clinical
    features there are no pathognomonic symptoms or
    signs. Many patients have fever, general aches
    and pains and malaise and are initially
    misdiagnosed as having flu.
  • P. falciparum malaria can be rapidly progressive
    and fatal. Prompt diagnosis saves lives and
    relies on astute clinical assessment
  • A good history
  • Residence or a recent visit (in the preceding 3
    months) to a malaria endemic area
  • History of fever (may be paroxysmal in nature)
  • Recognise significance of non-specific clinical
    features such as vomiting, diarrhoea, headache,
    malaise
  • Physical examination
  • Identify signs consistent with malaria fever,
    pallor, jaundice, splenomegaly
  • Exclude other possible causes of fever (e.g.
    signs of viral and bacterial infections)
  • The diagnosis of malaria should be considered in
    any unwell person who has been in a malarious
    area recently


32
Investigations
Blood Film Examination Thick and thin blood
films (or smears) have remained the gold
standard for the diagnosis of malaria. The films
are stained and examined by microscopy. Thick
blood film - Used for detecting malaria a
larger volume of blood is examined allowing
detection of even low levels of parasitaemia.
Also used for determining parasite density and
monitoring the response to treatment. Thin blood
film Gives more information about the parasite
morphology and, therefore, is used to identify
the particular infecting species of Plasmodium.
Show Me
Source- SOM 208 Microbiology Syllabus
Show Me
33
Thick blood film
  • A drop of blood is spread over a small area.
    When dry, the slide is stained with Fields or
    Giemsa stains. The red cells lyse leaving behind
    the parasites.
  • Used to detect parasites, even if parasitaemia is
    low
  • Less useful for speciation

Back
34
  • A small drop of blood is spread across a
    microscope slide, fixed in methanol and stained
    with Giemsa stain.
  • The microscopist finds the area of the film where
    red cells are lying next to each other. The fine
    details of the parasites can be examined to
    determine the species.
  • Used for speciation
  • Does not detect low parasitaemia

Thin blood film
Back
35
Appearance of P. falciparum in thin blood films
Ring forms or trophozoites many red cells
infected some with more than one parasite
Gametocytes (sexual stages) After a blood meal,
these forms will develop in the mosquito gut
http//phil.cdc.gov/phil/quicksearch.asp
36
Other methods of diagnosis of malaria
  • These are not routinely used in clinical
    practice. They include
  • Antigen capture kits. Uses a dipstick and a
    finger prick blood sample. Rapid test - results
    are available in 10-15 minutes. Expensive and
    sensitivity drops with decreasing parasitaemia.
  • PCR based techniques. Detects DNA or mRNA
    sequences specific to Plasmodium. Sensitivity and
    specificity high but test is expensive, takes
    several hours and requires technical expertise.
  • Fluorescent techniques. Relatively low
    specificity and sensitivity. Cannot identify the
    parasite species. Expensive and requires skilled
    personnel.
  • Serologic tests. Based on immunofluorescence
    detection of antibodies against Plasmodium
    species. Useful for epidemiologic and not
    diagnostic purposes.

37
Treatment
The treatment of malaria depends on a number of
factors which include
In the absence of reliable diagnosis, clinical
assessment alone can not differentiate malaria
from other common febrile illnesses. In this
situation, anti-malarial treatment should be
given routinely for people with fever.
38
Treatment of uncomplicated malaria single
agents
  • National treatment guidelines for first-line
    treatment are available in most malarious
    countries. Commonly used drugs include
  • 4-aminoquinolines - chloroquine
  • cheap and widely available and previously the
    most widely used antimalarial drug. Use is now
    severely limited because of widespread resistance
    of P. falciparum in South East Asia, East and
    West Africa.
  • blood schizonticide - kills the erythrocyte
    stages but has no effect on the exo-erythrocytic
    (liver) stages or gametocytes.
  • P. vivax is usually sensitive to chloroquine,
    although resistance is emerging.
  • Amodiaquine is an alternative for
    chloroquine-resistant falciparum malaria.
  • Sulphadoxine-pyrimethamine Fansidar first
    line treatment for P. falciparum malaria in many
    countries, although resistance to this drug has
    also developed rapidly.
  • 8- aminoquinolines Primaquine is active against
    the exo-erythrocytic forms of P. vivax and P.
    ovale and is added to treatment to prevent
    relapses.
  • Less commonly used drugs for first-line treatment
    are quinine, mefloquine (schizonticide
    neuropsychiatric adverse effects), halofantrine
    (schizonticide may cause cardiac arrhythmias and
    sudden death) and atovaquone-proguanil.

39
Treatment of uncomplicated malaria drug
combinations
  • The rapid emergence of resistance to drugs when
    used as single agents has led to the development
    of drug combinations for first-line treatment.
  • Combinations combine two or more schizonticidal
    drugs which act independantly of each other. This
    reduces the development of parasite resistance to
    the drugs used in the combination.
  • Artemisinin and its derivatives (artemether,
    artesunate, artheether based on the Chinese herb
    quinhaosu) are rapidly active against
    erythrocytic stages and also gametocytes
    (therefore, may reduce transmission). Current
    levels of resistance are low.
  • Several combinations include an artemisinin
    derivative e.g. dihydroartemisinin
    piperaquine artesunate chlorproguanil/dapsone
  • Examples of other drug combinations are
    chlorproguanil dapsone (Lapdap), atovaquone
    proguanil (Malarone).
  • The choice of which combination to use depends on
    many factors, including the existing pattern of
    resistance and cost.
  • As well as drug treatment, supportive treatment
    for associated problems such as high fever,
    dehydration and anaemia are important!

40
Treatment of severe, complicated malaria
  • Drugs
  • Quinine is the most widely used drug. It is
    administered by rate-controlled intravenous
    infusion. Where this is not possible, it can be
    administered by deep intramuscular injection.
    This is less desirable because of slow and
    uncertain absorption and risks such as injection
    abscess and muscle necrosis.
  • Artemisinin derivatives are also used to treat
    severe malaria. At rural clinics where it is not
    possible to give injections, artemesinin
    suppositories can be used whilst the patient is
    being transferred.
  • Supportive therapy
  • A vital adjunct to clinical management. It
    includes the general care of the unconscious
    patient, careful fluid balance, control of
    seizures, nasogastric tube feeding, correction of
    metabolic derrangements (e.g. hypoglycaemia,
    metabolic acidosis) and blood transfusion for
    severe anaemia.
  • Bacterial infection can also co-exist with severe
    malaria and require antibiotic treatment.

41
Malaria prevention and control Reducing
man-mosquito contact
Insecticide-treated nets (ITNs) are relatively
cheap and, if used correctly, an effective means
of preventing malaria. The development of
longlasting nets may help to overcome the
requirement to re-treat nets with insecticide
regularly. The major difficulty remains achieving
high coverage rates of ITNs in the most at-risk
populations. Historically, indoor house-spraying
with residual insecticides (e.g. DDT) achieved
many successes but was not sustainable. However,
some countries still use this approach as part of
their public health measures against
malaria. Other means to reduce contact for
individuals are wearing of protective clothing
and insect repellents at dawn and dusk.
Families are advised to prioritise the use of bed
nets for children under 5 years and pregnant
women the family members at most risk of
developing severe malaria.
42
Malaria prevention and control Chemoprophylaxis
  • Chemoprophylaxis is the administration of drugs
    to individuals likely to be exposed to malaria.
  • Indicated in travellers and also pregnant women
    and people with sickle cell disease living in
    malaria endemic areas
  • Effective malaria prophylaxis is challenging
    because of cost, drug resistance and adverse
    effects.
  • The recommendations vary according to likely
    parasite resistance and patient characteristics
    (e.g. age, breastfeeding, pregnancy).
  • Commonly-used drugs include chloroquine and
    proguanil, mefloquine and malarone.

43
Malaria prevention and control Vaccines against
P. falciparum -1
  • Why is a malaria vaccine needed?
  • Despite well-tested and proven public health
    interventions to prevent malaria, the disease
    burden due to malaria has increased in recent
    years. This has occurred for several reasons
  • Population growth
  • The parasite constantly develops resistance to
    the commonly-used and affordable drugs
  • Anopheles mosquitoes develop resistance to
    insecticide
  • Malaria control programmes are often not well
    implemented or are interrupted by conflict
  • Increased tourism and migration of non-immune
    people into malarious areas
  • A malaria vaccine offers the prospect of an
    affordable intervention that could be
    administered as part of existing immunisation
    programmes.

44
Malaria prevention and control Progress towards
a vaccine
  • Is a malaria vaccine possible?
  • There are several factors which suggest that
    immunisation against malaria is possible
  • Natural immunity against malaria develops after
    repeated exposure
  • Passive immunity occurs in young infants
    (probably as a result of maternal antibody) and
    also in individuals who were given purified
    immunoglobulins from people with natural immunity
  • Administration of UV attenuated sporozoites
    confers protection
  • Experimental malaria vaccines have shown some
    modest efficacy in clinical trials
  • So why is developing a vaccine difficult?
  • There are several obstacles
  • P. falciparum is a highly complex parasite with
    different antigens at different stages of the
    life cycle
  • Many of these antigens show marked polymorphism
  • Single parasite clones show antigenic
    variability the parasite constantly changes its
    antigens
  • The basis of naturally-acquired immunity is not
    well understood
  • There is no animal model to help with the
    development and testing of vaccine candidates

45
Malaria prevention and control What vaccines are
under development?
There are around 75 candidate vaccines under
development. Vaccines can be grouped according to
the stage of the parasite life cycle
Pre-erythrocytic aim to prevent clinical disease
by targetting sporozoites and intra-hepatocytes
stages
Transmission-blocking aim to prevent
human-to-human transmission by targeting the
sexual stages in the mosquito
Erythrocytic or blood stage aim to reduce
disease severity by preventing invasion or
increasing the clearance of red cells.
46
Malaria prevention and control What are the
leading vaccine candidates?
  • There are hundreds of parasite proteins which
    could form targets for vaccines. Various
    strategies of stimulating the hosts immune
    response are being evaluated including
    prime-boost, virosomes and synthetic parasite
    peptides. Most of the vaccines currently under
    development are targeted against
  • the circumsporozoite protein (CSP)
  • the merozoite surface protein (MSP)
  • the apical membrane antigen (AMA-1)
  • The most advanced vaccine to date, RTS,S/AS02A,
    has been developed jointly by GlaxoSmithKline and
    the Malaria Vaccine Initiative. It is a
    pre-erythrocytic, sub-unit vaccine which combines
    CSP with the hepatitis-B surface antigen.
    Clinical trials have shown that this vaccine
    reduced malaria episodes by 30 and severe
    malaria by 58 in children in Mozambique.

47
Malaria in pregnancy
  • More than 45 million women (30 million in Africa)
    become pregnant in malaria endemic areas each
    year. The adverse effects of malaria affect
    primigravidae more than multigravidae and HIV
    infection increases malaria in pregnancy. The
    following adverse events are well-recognised
  • Mother
  • Anaemia
  • Cerebral malaria
  • Hypoglycaemia
  • Puerperal sepsis
  • Pulmonary oedema and heamorrhage
  • Fetus
  • Abortion and stillbirth
  • Preterm delivery
  • Intra-uterine growth retardation (IUGR) and
    anaemia
  • Infant
  • Low birth weight (lt2500 gms both prematurity and
    IUGR may contribute)
  • Reduced levels of maternal antibody (e.g. against
    tetanus)

48
Malaria in pregnancyPrevention and control
  • As usual, this requires using more than one
    approach that are appropriate to the local
    situation. The following are key components of
    malaria control programmes for pregnant women
    recommended by WHO
  • Prompt and effective case management according to
    national treatment guidelines. Commonly used
    drugs include chloroquine, sulfadoxine-pyrimethami
    ne and quinine.
  • Insecticide-treated mosquito nets (ITNs)
  • Intermittent preventive treatment (IPT) the
    administration of an anti-malarial drug (e.g.
    sulphadoxine-pyrimethamine) in areas of stable
    malaria transmission whether or not women show
    symptoms or have parasites in the blood. 3 full
    doses are given at least 1 month apart during the
    second and third trimesters. IPT has now replaced
    chemoprophylaxis (e.g. with chloroquine) in many
    countries.

Source http//phil.cdc.gov/phil/quicksearch.asp
49
International initiatives
  • Many international organisations are involved in
    the fight against malaria.
  • The WHO in partnership with UNICEF, UNDP and the
    World Bank initiated Roll Back Malaria (RBM) in
    1998 to promote an effective control strategy to
    combat the disease. The goal of RBM is to halve
    the worlds burden of malaria by 2010. RBM was
    later joined by a broader group of partners
    including governments of countries affected by
    the disease, multi and bilateral agencies, NGOs,
    international private sector representative and
    research groups.
  • RBM focuses on
  • Rapid clinical case detection and provision of
    prompt access to effective malaria treatment,
    especially in the home.
  • Preventing and controlling malaria during
    pregnancy.
  • Promoting the use of insecticide treated bed
    nets (ITN) as a means of prevention, especially
    in young children and pregnant women.
  • Dealing effectively with malaria in emergency
    and epidemic situations.

Prompt effective malaria treatment saves lives
50
End of Section 4
  • You have come a long way!
  • This is the last of the sections.
  • For the section just ended, you should be able to
    answer Question 5 to assess what you have learnt.
    It is still required that you put down your
    answers on the mark sheet before looking at the
    right answer!

51
Question 5 Malaria diagnosis, prevention and
treatmentWrite T or F on the answer sheet.
When you have completed all 6 questions, click on
the box and mark your answers.
7. Quiz 1
Click for the correct answer
  • A well-prepared and stained thick blood film is
    usually the most practical way to diagnose
    malaria
  • Chloroquine prophylaxis is recommended during
    pregnancy in East Africa
  • More than one anti-malarial drug should be used
    for first-line treatment
  • Quinine is the drug of choice for severe malaria
  • Poor compliance with antimalarial therapy favours
    the development of resistance
  • Insecticide-impregnated bednets are used to
    prevent malaria mainly in travellers

a
b
c
d
e
f
52
Sources of information
  • Malaria. Greenwood BM, Bojang K, Whitty CJ,
    Targett GA. Review Lancet 2005 3651487-98.
  • http//mosquito.who.int/cmc_upload/0/000/015/372/R
    BMInfosheet_1.htm
  • These WHO fact sheets developed by the Roll Back
    Malaria Partnership cover many different aspects
    of malaria including prevention with
    insecticide-treated bed nets and treatment with
    atemesinin-based combination therapies
  • http//www.cdc.gov/malaria/
  • The US Centre for Disease Control and Prevention
    site for malaria
  • http//www.malaria.org/
  • Follow the Learn about malaria link on the
    Malaria Foundations website. This contains
    numerous useful and accessible resources.
  • http//www.rph.wa.gov.au/labs/haem/malaria/
  • An interactive resource from the Royal Perth
    Hospital, Western Australia. Contains useful
    self-assessment exercises in malaria diagnosis by
    microscopy that are set in the context of
    clinical cases.
  • Towards an effective malaria vaccine. Aide P,
    Bassat Q, Alonso P. Arch Dis Child 200792476-9.
  • Malaria. A handbook for Health Professionals.
    Malaria Consortium. Macmillan Publishers Limited
    2007.

53
End of Module
  • Well done!
  • Now that you have completed the malaria module
    and attempted sectional questions, you may wish
    to take on the full quiz to assess your learning
    for the whole module. Please print out the
    questions
  • The questions may differ slightly from those you
    have come across in the sectional assessment but
    are based on the material covered in this module.
  • END OF MODULE QUIZ
  • You will also find a link to the answers at the
    end of the quiz to measure your performance
  • Please attempt this as many times as you wish.

54
Authors and reviewer
  • Expert reviewer
  • We would like to thank Professor Olugbemiro
    Sodeinde, College of Medicine, University of
    Ibadan, Ibadan, Nigeria for reviewing this module
  • Permissions
  • Please note that verbal permission was granted
    from parents to use the images in this module for
    teaching purposes only. The images should not be
    used for any other purpose.
  • Latest update April 2008
  • Authors
  • Dr. Ike Lagunju, Consultant Paediatrician and
    Associate Lecturer, College of Medicine,
    University of Ibadan, Ibadan, Nigeria.
  • Dr. David Lewis, Learning Technologist, and Dr.
    Stephen Allen, Reader in Paediatrics and Honorary
    Consultant Paediatrician, The School of Medicine,
    Swansea University, Swansea, UK
  • We would like to acknowledge the Association of
    Commonwealth Universities, London for awarding
    the Fulton Fellowship which supported Dr. Lagunju
    in developing this module

We are very interested to receive feedback
regarding any aspect of this module especially
if it helps us to improve it as a learning
resource. Please e mail any comments to either
s.j.allen_at_swansea.ac.uk or ilagunju_at_hotmail.com F
or further information about the Partnership in
Global Health Education, visit
http//www.medicine.swan.ac.uk/inthealth.html
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