‫بسم ا الرحمن الرحيم‬

‫جاماعة ام درماان السالماية ‪/‬كلية الطب و العلوم الصحية‪ /‬قسم طب المجتمع ‪ /‬الدفعة ‪26‬‬

‫‪Malaria‬‬
‫اعداد د‪ .‬نائلة مبارك كركساوى‬
• Malaria is:
• a mosquito-borne (Vector-borne) infectious
protozoan disease.
• It is caused by a parasite of the genus
plasmodium
• It is transmitted only by female mosquitoes of
the genus Anopheles.
• Countries in tropical Africa account for more
than 90% of cases.
• high risk groups include:
• young children, especially in remote rural
areas with poor access to health services.
• women during pregnancy,
• refugees,
• displaced persons,
• or labour forces entering into endemic areas
• A person who has been successfully treated
with antimalarial drugs may be healthy but?
• infective for about 2 months until?
• the gametocytes die off naturally,
• or until?
• another drug such as primaquine (that
eliminates the gametocytes), is given.
• In highly endemic areas, persons repeatedly
infected with malaria?
• acquire a degree of immunity which?
• suppresses most clinical symptoms, but?
• may carry gametocytes in their blood that ?
• And so infect the mosquitoes biting them
• Plasmodium falciparum causes?
• the most serious,
• severe
• and prevalent disease (40-60% of cases),
• it contributes to a widespread chloroquine
resistance malaria
Causative agents:
• In humans, malaria infection is caused by?
• one or more of four species of intracellular
protozoa.
• The four species of plasmodium causing
human malaria are:
• P falciparum,
• P vivax,
• P ovale,
• P malariae.
These four species differ:
• 1- morphologically, & immunologically,
• 2-in geographical distribution,
• 3-relapse pattern,
• 4-drug response,
• 5-clinical features:
• periodicity of infection, potential for severe
disease, and ability to cause relapses ,
• 6-potential for development of resistance to
antimalarial drugs.
Anopheles mosquitoes:
• Malaria vectors that belong to the A. gambiae
are widely distributed in tropical Africa.
• They are not usually found more than 2 or 3
kilometers from their breeding places in large
number.
• However, strong seasonal winds may carry
Anopheles up to 30 km from their main
breeding place.
Reservoir:
• Chimpanzees and gorillas are the natural
reservoir for P. malariae.
Incubation period:
• usually 9 - 30 days, depending on the infecting
species (shortest for P. falciparum, longer for P.
malariae).
• In some strains of P. vivax the incubation
period may last some 8-9 months.
Malaria Life Cycle:
• The life cycle of all species that infect humans
is basically the same.
1- Exogenous sexual phase ( sporogony) during
which the parasite multiplies in the mosquito.
• A-This phase starts when the gametocytes
(found close to the skin surface of the host )
and are sucked up by a mosquito together
with blood.
• B-Gametocytes migrate into the salivary
glands of the mosquito and a new cycle of
infection begins.
• C-Micro and macrogametocytes are fertilized
in mosquito stomach.
• D-Ookinete formed: penetrates gut wall; forms
oocysts.
• E-Sporozoites develop in cyst in 7-10 days.
• F-Sporozoites then enter blood of a new host
with mosquito bite.
2- Endogenous asexual phase: This phase goes
as two parts:
(a)Exo-erythrocytic (liver) phase:
Blood of the host, is infected with sporozoites
about 30 minutes after the mosquito bite .
The sporozoites enter the liver cells where they
multiply for 5–12 days forming:
hepatic schizonts
. Schizonts rupture: releasing merozoites which
invade red blood cells (RBCs).
(b) Erythrocytic phase (in RBCs):
Merozoites infect RBCs. Trophozoites :are Early
stages in this phase
Trophozoites form schizonts.
Schizonts forms merozoites..
Merozoites invade other RBCs
and schizogony is repeated .
• Parasite density increases until?
• host’s immune response slows it down?
causing malaria sign & symptoms .
• Some merozoites differentiate into?
• male or female gametocytes, (the sexual
forms of the parasite)
Epidemiological profile:
• 1. Areas of high transmission=
• reported malaria case incidence from all
species is 1 or > per 1000 population / year.
• 2. Areas of low transmission= reported
malaria case incidence from all species is < 1
per 1000 population / year, but > zero.
• Transmission in these areas is generally highly
seasonal with or without epidemic peaks
Malaria-free areas:
• where there is NO , local mosquito-borne
malaria transmission and ALL malaria cases
are introduced.
• An area is designated malaria-free when no
cases have occurred for several years.
• Areas may be malaria-free due to:
• environmental factors
• or as a result of effective control efforts.
In practice, malaria-free areas can only be
accurately designated by:
national programmes taking into account ?
• the local epidemiological situation
• and entomological investigations.
Definitions:
• Asexual parasitaemia:
• The presence of asexual parasites in RBCs of
the host.
• The level of asexual parasitaemia can be
expressed in several different ways e.g.:
• a- the number of infected RBCs / unit volume
of blood,
• b- the number of parasites seen in one
microscopic field in a high-power examination
of a thick blood film.
 Asexual cycle.
• It The life cycle of the malaria parasite in the
host, is from :
• merozoite invasion of red blood cells to
schizont rupture
• (merozoite ring stage trophozoite
schizont merozoites).
• Duration is approximately: 48 h in P. falciparum
• , P. ovale and P. vivax and: 72 h in P. malariae
• Ring stage:
• Young usually ring-shaped intra-erythrocytic
malaria parasites, before malaria pigment is
evident under microscopy
• Malaria pigment :
• is most abundant and distinct in gametocytes.
Trophozoites have variable amounts of
pigment, depending on the species of
Plasmodium and the stage of infection.
• Merozoites: Parasites released into the host
bloodstream when a hepatic or erythrocytic
schizont bursts. These then invade the RBCs.
• Ring stage:
• Trophozoites: Stage of development of the
malaria parasites within host RBCs: from the
ring stage and before schizonts formation.
• Schizonts: Mature malaria parasites in host liver
cells (hepatic schizonts) or RBCs (erythrocytic
schizonts) .
• Sporozoites: Motile malaria parasites that are
infective to humans, are inoculated by a
feeding female anopheline to human host.
They invade host hepatocytes.
• Hypnozoites: Persistent liver stages of P. vivax
and P. ovale malaria that remain dormant in
host hepatocytes for a fixed interval (3–45
weeks) before maturing to hepatic schizonts.
• Recurrence:
• is the recurrence of asexual parasitaemia
caused by a recrudescence, a relapse or a new
infection.
• Relapse:
• The recurrence of asexual parasitaemia in P.
vivax and P. ovale malaria,
• it occurs when the infection has been
eliminated from blood ,
• but hypnozoites persist in the liver and mature
to form hepatic schizonts.
• When hepatic schizonts burst, they liberate
merozoites into the bloodstream,
• and produce clinical relapse.
• Recrudescence: This results from incomplete
clearance of parasitaemia by treatment, this
leads to the recurrence of asexual
parasitaemia with the same infection that
caused the original illness.
• Population at risk: Are the total population
living in areas, where malaria is endemic (low
and high transmission).
• Pathology and immunology:
• Symptoms of malaria are due to release of
massive number of merozoites into circulation.
• Results in:
• 1- the production of antibodies which are
effective in containing the parasite load.
• These antibodies are against merozoites and
schizonts.
• 2- The infection also results in the activation of
the reticuloendothelial system (phagocytes).
• The activated macrophages help in destruction
of infected erythrocytes & antibody coated
merozoites.
• 3-Cell mediated immunity also may develop
and help in the elimination of infected
erythrocytes.
• Types of Malaria in Humans
• 1- Plasmodium vivax :( Benign tertian malaria):
Cycles of paroxysms; every 48 hours.
• 2-Plasmodium ovale (Mild tertian malaria):
Cycles of paroxysms; every 48 hours
• 3-.Plasmodium falciparum: (Malignant
tertian): Most severe and prevalent (40-60%
of cases).Widespread chloroquine resistance .
Heavy parasitaemia
• 4-Plasmodium malariae (Quartan malaria):
Cycles of paroxysms; every 72 hours
cosmopolitan distribution - about 7% of
human malaria
Clinical presentation:
• Varies in severity and course depending on:
• a- Parasite factors (Species, geographic origin
of parasite & size of inoculum of parasite)
• b-Host factors (age, immune status, general
health condition and nutritional status
&Chemoprophylaxis used) .
• c-Mode of transmission (by a mosquito, blood
borne: transplacental)
Malarial Paroxysm
• 1- Prodrome (Early symptoms), 2-3 days:
Malaise, fatigue, muscle pains, nausea, anorexia,
Headache, Slight diarrhea, periodic febrile
paroxysms every 48 – 72 hours
• 2- Paroxysm: Cold stage : rigors. Hot stage –
temp. can reach 40-41o C, splenomegaly
.Sweating stage .Lasts 8-12 hours, start between
midnight & midday
• 3-Periodicity:Days1 &3 for P.v., P.o., P.f. = tertian.
• Days 1 & 4 for P.m. = quartan
Congenital malaria:
1- Transplacental infection:
• Can be by all 4 species .
• Commonly P.v. and P.f. in endemic areas,
2- Neonate can be diagnosed within 7 days of
birth or longer
3- acquired immunity: from mother to child give
3-6 months protection.
A guide to diagnostic and treatment methods:
• 1. Effective diagnosis and treatment should be
available at all health facilities.
• 2. Where a health facility is not accessible to
the majority of people (within 24 hours of the
onset of illness), diagnosis & treatment should
be provided through a programme of home
based management of malaria.
• 3. Malaria services should be made available
at affordable prices & with quality assurance.
• 4. Treatment with artemisinins/quinine, should
be at primary health care facilities for severe
malaria followed by immediate referral to
higher levels of the health system,
• 5. Rectal artemisinins should be at community
level, for severe malaria in children < 5 years
and followed up with referral to a higher levels
health facility
• 6. The use of monotherapies in the treatment
of P. falciparum malaria should be abandoned
Diagnosis of malaria:
• A- The clinical diagnosis
• B- Direct microscopic examination:
C- Rapid diagnostic test (RDT) i.e. Antigen
detection tests :
• using rapid immunochromatographic
techniques.
D- polymerase-chain reaction (PCR) :
• more frequently used in the diagnosis of
malaria,
• & drug resistance in malaria.
Anti Malarial Drugs
• 1- Chloroquine:
• is a synthetic 4-aminoquinoline, which is a
highly effective blood schizonticide
• It is the cheapest, and rapidly controls acute
attack of malaria with most patients becoming
afebrile within 24-48 hours.
• It is safer than quinine & available as
Chloroquine phosphate tablets; each 250-mg
tablet contains 150 mg of the base &
Chloroquine hydrochloride injection contains
40 mg of the base per ml.
• Chloroquine is not active against liver stage
parasites.
• Resistance to chloroquine developed in the
1960s
• & is now very common among strains of P
falciparum
• and some degree of resistance is now seen in
all endemic regions in Africa .
2- Chloroguanide (Proguanil):
• is available as tablets, each containing 100 mg
of the drug.
• The dose for prophylaxis is 100-200 mg daily.
• Chloroguanide along with chloroquine is used
as prophylaxis effective against P. falciparum
malaria.
• It is a safe drug and can be used in pregnancy.
3- Amodiaquine :
• Amodiaquine has been widely used to treat
malaria in many countries because of:
• its low cost, limited toxicity, and, in some
areas, effectiveness against chloroquine-
resistant strains of P falciparum.
4-Primaquine:
• is the essential co-drug with chloroquine in
treating malaria.
• It is highly effective against the gametocytes of
all plasmodia and thereby prevents spread of
the disease to the mosquito from the patient.
• It is also effective against the dormant tissue
forms of P. vivax and P. ovale malaria, and
thereby offers radical cure and prevents
relapses.
5- Quinine:
• is obtained entirely from the natural sources due
the difficulties in synthesizing the complex
molecule.
• Quinine acts as a blood schizonticide (it is less
effective and more toxic than chloroquine),
• it also has gametocytocidal activity against P.
vivax and P. malariae.
• It is used in the management of severe
falciparum malaria in areas with known
resistance to chloroquine.
• Resistance to quinine is uncommon but increasing.
• Quinine is a potentially toxic drug.
• It is available as tablets and capsules containing 300 or
600 mg of the base.
• It is also available as injections, containing 300mg /ml.
• Dose: Oral- 10 mg/kg 8 hourly for 4 days and 5 mg/kg 8
hourly for 3 days.
• IV: 20 mg of salt/kg in 10 ml/kg isotonic saline or 5%
dextrose over 4 hours, then 10 mg of salt/kg in saline or
dextrose over 4 hours, every 8 hours until patient is able
to take orally or for 5-7 days.
• IM: 20 mg/kg start, followed by 10 mg/kg 8 hourly by
deep intra muscular injections for 5-7 days
7- Artemisinin Derivatives:
Artemisinin:
• Recommended by WHO for the treatment of
cerebral malaria & for the control of multi-
drug resistant P. falciparum malaria.
• A water soluble artesunate &two oil soluble
preparations called artemether and arteether
are developed.
• These drugs start acting within 12 hours.
• Artesunate and artemether have been shown
to clear parasitaemias more effectively than
chloroquine and sulfadoxine/pyrimethamine.
Artemether: Available as 80mg/ml Injection and
40mg per capsule
• Injection: 3.2 mg/kg intra muscularly as a
loading dose, followed by 1.6 mg/kg daily a
maximum of 7 days.
• Oral: 4mg/kg on first day followed by 2mg/kg
for 6 days.
Arteether: Available as 150mg per 2 ml ampoule
.Dose: 3 mg/kg once a day for 3 days, as deep
intra muscular injection.
Artesunate: it is available as 50mg tablets and
60mg/ml injection.
• Oral: 4 mg/kg on the first day followed by
2mg/kg for 6 days. It can also be used in
combination; 4mg/kg on the second and third
days with mefloquine 15 mg/kg in a single
dose on the second day. Oral artesunate is not
recommended in pregnancy.
8- Combined tablets of Pyrimethamine &
Sulphadoxine :
• are very useful in the treatment of :
• uncomplicated,
• chloroquine resistant, P. falciparum malaria.
• Combined tablets are available, containing 25
mg of pyrimethamine and 500 mg of
sulphadoxine in each tablet.
9- Halofantrine hydrochloride:
• is effective against erythrocytic stages of all
four human malaria species,
• effective against multi drug resistant P.
falciparum malaria ,
• but its use is limited by irregular absorption
and cardiac toxicity.
• It is not active against hepatic stages or
gametocytes.
• It is available only as a tablet.
Dose:
• For adults, 3tablets of 500 mg each, 6 hours
apart.
• For children, 3 doses of 8 mg/kg of the salt 6
hours apart.
• Treatment should be repeated after 7 days.
10-Mefloquine hydrochloride tabs:
• is chemically related to quinine.
• It is effective against falciparum malaria,
including the chloroquine resistant types.
• It is available as 250 mg tablets.
• Dose: 15 mg/kg in a single dose.
• Total dose should not exceed 1500 mg.
Mefloquine has:
• strong blood schizontocidal activity against P
falciparum and P vivax,
• but it is not active against hepatic stages or
gametocytes.
• Sporadic resistance to mefloquine has been
reported from many areas.
Drug Resistance:
• a challenging problem in malaria control
• Since early 60s the sensitivity of the parasites
to chloroquine has been on the decline.
• Newer antimalarials were discovered in an
effort to tackle this problem,
• but all these drugs are either expensive or
have undesirable side effects.
• Moreover after a variable length of time, the
parasites, especially the falciparum species,
have started showing resistance to these
drugs also.
Definition:
• Drug resistance is the ability of the parasite
species 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 limit of
tolerance.
• Drug resistance is most commonly seen in P.
falciparum.
Treatment of drug-resistant malaria:
• 1- Since chloroquine is a cheap and effective
drug with very little side effect?
• it should be the drug of choice for
uncomplicated malaria even in areas of known
resistance to chloroquine.
• Only when recrudescence develops other
drugs should be considered.
2- Areas with resistance to chloroquine, but
sensitivity to Pyrimethamine/sulpha:
a- Non-immune, uncomplicated malaria:-
• Quinine 600 mg orally every 8 hours for 5
days,
• followed by a single dose of three tablets of
Pyrimethamine/ sulphadoxine.
b- Semi-immune- :
• A single dose of three tablets of
Pyrimethamine/ sulphadoxine should be
given.
3-Areas with resistance to both chloroquine and
Pyrimethamine:
• Quinine should be given for 7 days.
 4- Areas with resistance to chloroquine,
Pyrimethamine and poor response to quinine:
Quinine for 7 days with tetracycline 250 mg
every 6 hours for 7 days.
(Tetracycline is contraindicated in children below
8 years and pregnant women).
Malaria Control:
• The control of malaria involves control of 3 living
beings and their environment.
• A-Man (The host):
• can take the disease with him too far and wide.
• B-Mosquitoes (The vector):
• highly adaptable and have shown resistance to
insecticides. It is therefore important to target
non-flying eggs and larvae.
• C-The parasite (The agent):
• highly adaptable, has also developed resistance
to drugs.
• Therefore, for effective malaria control?
• target man first,
• control Anopheles mosquitoes next
• and keep trying to tackle the Plasmodia
parasite with development of effective drugs
and vaccines.
• control of malaria is a formidable task.
A- The Vector Control :
• Vector control aims :
• to decrease contacts between humans and
vectors of human disease (Mosquitoes)
• Elimination of malaria in an area does not
require the elimination of all Anopheles
Mosquitoes capable of transmitting the
disease.
• In North America and Europe:
• Anopheles mosquitoes capable of transmitting
malaria are still present,
• but the parasite has been eliminated.
• Socio-economic improvements (e.g., houses
with screened windows, air conditioning)
• combined with vector reduction efforts
• and effective treatment
• has led to the elimination of malaria without
the complete elimination of the vectors.
• Vector control for the prevention of malaria
includes:
• −Control of breeding sites (water), i.e. source
reduction ( larval control )
• −Insecticide use (residual spraying Indoor &
around houses)
• −Reduction in exposure (Insecticide- treated
bed nets, screens, repellants)
Source Reduction :
• It involves preventing development of mosquito
larvae.
• It is an ideal approach to mosquito control.
• The female anopheles mosquito lays eggs in
collections of clean water.
• Each female anopheles mosquito lays millions of
eggs in its lifetime of 4-8 weeks.
• The eggs hatch into larvae, which then develop
into pupae and adults in a span of 7-10 days.
• The best method of mosquito control is:
• preventing the development of the eggs into
adult mosquitoes.
Anti larval measures in malaria control include
the following:
Preventing egg laying:
• This is done by avoiding or eliminating the
clean water collections.
• Most such collections are manmade:
• 1- It is common habit to throw the unutilized
utensils, buckets, bottles etc.
• During the rains, water gets collected in these
containers provides ample breeding locations
for the female anopheles mosquito.
• 2- Shortages of water supply makes it
necessary to have tanks, that are often left
uncovered and this provides scope for
mosquito breeding.
• 3-Puddles of water it is common to find
everywhere during the rainy season.
• This is the reason why malarial transmission is
at its peak during the monsoon.
• 4-Unused well.
Use of Larvicides:
• This can be done by :-
i. Chemicals: Mosquitoes that breed in irrigation
water can be controlled through careful water
management.
• Oils may be applied to the water surface,
suffocating the larvae and pupae.
ii. Biological larvicides:
• Guppy and Gambusia fish are known for their
larvivorous habits.
• These fish eat the developing larvae and
thereby effectively control the mosquito
population.
•
B- Other Vector Control Methods: Personal
protection measures include:-
• 1-Protective clothing (light-colored clothes,
long pants and long-sleeved shirts) helps to
keep the mosquitoes away when the
individual is relaxing either indoors or
outdoors, particularly between 6PM and 10
PM
• 2-Well-constructed houses with window
screens are effective for preventing biting by
mosquitoes that bite indoors.
• 3-Preventing the mosquitoes from hiding:
Anopheles mosquitoes tend to hide in the
dark corners and amidst the clothes left
hanging in the rooms. During the night, they
come out of their hiding to seek human blood.
4- Mosquito Repellents:
• (a):- natural repellents ,Essential oils from
plant extracts that act as natural repellents are
lemongrass oil and neem oil
• (b);- chemical repellents
4- Insecticide vaporizers:
• including mosquito coils, liquid vaporizers,
aerosols &vaporizing mats .
• Insecticide Vaporizers may not be safe .
5- Mosquito nets:
• are the best and safest means of protection
against mosquito bites during nights, the peak
biting time for the female anopheles.
• Insecticide treated bed nets (ITNs) in malaria
control in endemic areas.
• Many types are available depending on the
size, material (polyester, cotton, polyethylene)
and treatment with insecticides.
• However, mosquitoes can feed on people
through the nets, even a few small holes,
• Nets should be strong and with a mesh size no
larger than 1.5 mm.
7-Man's Role in Malaria Control:
• This includes education of doctors about the
need for early diagnosis and prompt
treatment of malaria.
• Treat completely to prevent spread and
relapse .
• Ensure compliance with complete treatment.
• Personal Protection:
• prevents malaria by using bed nets,
• insecticide sprays etc.,
• and by chemoprophylaxis.
C- Adult Mosquito Control: involve the
following measures:
• 1-Preventing entry of adult mosquitoes into
human dwellings .
• 2-Personal protection measures
• 4-Mosquito repellents .
• 5-Insecticide vaporizers .
• 6-Mosquito nets (regular and insecticide
treated) .
• IRS does not directly prevent people from
being bitten by mosquitoes.
• Rather, it usually kills mosquitoes after they
have fed, if they come to rest on the sprayed
surface.
• IRS thus prevents transmission of infection to
other persons.
• To be effective, IRS must be applied to a very
high proportion of households in an area
(usually >70%).
• Space sprays : for instant results
• Residual sprays : for sustained effects .
• Air-conditioning is a highly effective means of
keeping mosquitoes and other insects out of a
room.
Early diagnosis and treatment:
• This is a very important aspect of malaria
control. By this, the parasite load in the
community is reduced; thereby reducing the
transmission of the disease.
• Tests for malaria parasite should be done in all
cases of fever, and treatment with first full
dose of chloroquine should be administered.
Whenever resistance to chloroquine is known
or suspected, second line anti malarial should
be used.
Radical treatment:
• All confirmed cases of fever should be
administered radical treatment with
primaquine.
• A single dose of primaquine must be
administered in P. falciparum malaria to sterilize
the gametocytes.
• A 14 days course of primaquine should be
administered in P. vivax infection to destroy the
hypnozoites in the liver and thus to prevent
relapse.
Fogging or area spraying is primarily reserved
for:
emergency situations:
halting epidemics
or rapidly reducing adult mosquito populations
when they have become severe pests.
Fogging and area sprays must be properly timed
to coincide with the time of peak adult
activity, because resting mosquitoes are often
found in areas that are difficult for the
insecticide to reach (e.g. under leaves).
Vaccination:
No effective malaria vaccines exist Major efforts
to produce vaccines against multiple life
Stages (i.e. Sporozoites, Hepatic stages, Blood
stages, Gametes/gametocytes), are underway.
The combination of tools and methods to
combat malaria includes:-
• (a)- long-lasting insecticidal nets (LLIN)
• (b)- artemisinin-based combination therapy
(ACT), supported by
• (c)- indoor residual spraying of insecticide (IRS)
and
• (d)- Intermittent preventive treatment in
pregnancy (IPT).
‫و بال التوفيق‬