COMMUNICABLE DISEASES (IM)
Topic: Malaria
Lecture by: Dr. Fortuno
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MALARIA
Malaria is a mosquito-borne infectious disease caused by a
eukaryotic protist of the genus Plasmodium
Mal (Bad) + Aria (Air) = Malaria (Bad Air)
o
This “bad air” was believed to be the cause of the fever
that often developed in those who spent time around the
swamps.
o
In fact, the illness, now known as malaria, was due to
certain protozoon present in the mosquitoes that bred
around these swamps, and which caused recurring
feverish symptoms in those they bit
Picture Above: Estimated cases and deaths in Asia (2010)
This just shows that here in the Philippines  there is a decreasing number
of case and deaths due to malaria (as compared to other countries)
Picture Above: Distribution map of malaria
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We always say that malaria is a disease of the tropics. Tropics  areas
between the tropical belts of Capricorn and Cancer, with the equator in the
middle. At the map, all the areas encompassed by tropics of Cancer and
Capricorn are all tropical countries (they are different from the temperate
countries that are outside the tropical belt). In tropical countries, there are
diseases inherent to them because of the humidity and temperature 
making some diseases conducive for its inhabitance
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Malaria:
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OVERVIEW
Most important parasitic disease in humans globally.
Causes a heavy burden among tropical countries.
This is because the vector that carries malaria thrives in
environments of tropical countries
Poses a threat to non – endemic countries.
Poses a danger to international and local travelers.
Transmission of Culex us almost nil; Anopheles need large size of
fresh water to survive
Disease caused by protozoan parasites called Plasmodium.
It is usually transmitted through the bite of an infected female
Anopheles mosquito.
Malaria may also be transmitted through the following:
o
Transfusing blood that is positive for malaria parasites
This is because malaria parasites reside in the RBCs
o
o
Sharing of IV needles (especially among IV drug users)
Transplacental (transfer of malaria parasites from an
infected mother to her unborn child)
LIFE CYCLE
Picture Above: Malaria Program Phases
How is the Philippines faring in terms of contribution to global deaths due to
malaria? Our country is shaded in light blue  little by little the Philippines
contributes less and less number of deaths secondary to malaria in terms of
worldwide statistics. Even the countries around use like Thailand, Cambodia,
Lao PDR, & Vietnam  there is also decrease in malaria prevalence and death
cases. However, there are countries a little bit far from us that have
contributed highly to the global statistics of deaths due to malaria
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Page 1 of 9
COMMUNICABLE DISEASES (IM)
Topic: Malaria
Lecture by: Dr. Fortuno
Explanation of the Life Cycle of Malaria Parasite:

An infected mosquito will try to bite the human host. Remember that the
mosquito should be an infected Anopheles. The human host will receive all
the saliva coming from the mosquito  the parasites received are called
sporozoites. The sporozoites will go to the liver, and depending on the specie
of the Plasmodium, they may reside in the liver for a longer time or the
sporozoites may burst from the hepatocytes  released into the blood
circulation. Once the sporozoites are inside the liver, this is called
extraerythrocytic life cycle of plasmodium. Eventually, the hepatocytes will
burst  parasites coming out are now called merozoites, they will attach
themselves to the RBCs (depending on the specie, they attach to specific
RBCs). The merozoites will go inside the RBCs to change its internal milieu so
that it will be conducive for it to replicate. Once its replicates in the RBC 
this is now called the erythrocytic life cycle of plasmodium. One replication
of merozoite in the RBC will be able to release hundreds of merozoites (this
depends again in the specie of Plasmodium). The released merozoites will
infect naïve or unaffected RBCs. Inside the RBC is what we called the
gametocytes (merozoites become male or female gemetocytes). In the
human blood, these gametocytes will not reproduce  they will just be
freely swimming in the circulation until a mosquito (infected or uninfected)
bites the human host  gametocytes are sucked by the mosquitoes. Inside
the body of the mosquito, the gametocytes will reproduce and they will
release the male & female gametes. The gametes will eventually mature to
become sporozoites inside the mosquito gut.
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During the early stage of intraerythryocytic development, small
“ring” of the different species s appear similar
By the end of 48 intraerythrocytic stage (24 for knowlesi, 72 for
malariae), the parasite has consumed two thirds of the hemoglobin
and is now called a schizont
Multiple nuclear division have taken place (schizogony or merogony)
and the RBC then ruptures to release 6-30 merozoites, each can
infect RBC
The disease in humans is caused by direct effects of RBC invasion and
destruction by the asexual parasite and the host’s reaction
After a series of asexual cycles (p. falciparum), or immediately after
release from the liver (vivax, ovale, malariae, knowlesi), some
parasites develop into gametocytes that can transmit the malaria
Male and female gametocytes form zygote in the insect’s midgut
Zygote then matures into ookinete which encyst in the gut wall
The resulting oocyst expands by asexual division until it bursts to
liberate sporozoites which then migrate to the hemolymph to the
salivary gland of the insect
Sexual Life Cycle of Plasmodium  it is inside the mosquito gut
Asexual Life Cycle of Plasmodium  it is inside the human host
Definitive host of Plasmodium  mosquitoes (because the sexual life cycle
happens inside them)
Summary of Plasmodium Life Cycle:
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Step 1: The mosquito takes a blood meal from an infective individual.
Sporozoites (the sexual phase) occurs in the gut of the mosquito.
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Step 2: preerythrocytic stage. Asexually reproduce can be as many as
100,000 merozoites  rupture of hepatic cell  attach to RBC
(erythrocytic stage)
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Step 3: erythrocytic stage. Asexual stage. 1 merozoite infects 1 RBC
 asexually reproduce then the RBC bursts
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Step 4: not reproduce sexually in humans. The female and male
gametocytes need to be sucked by the mosquitoes
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Step 5: oocyst release several sporozoites in the abdomen
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ETIOLOGY AND PATHOGENESIS
Human infection begins when a female anopheline mosquito
inoculatrs plasmodial sporozoites from its salivary gland during a
blood meal
These motile forms of the malarial parasite are carried rapidly via the
bloodstream to the liver, where they invade hepatic cells and begin
asexual reproduction
This amplification process is also known as intrahepatic or
preerythrocytic schizogony or merogony
Swollen infected hepatic cell eventually burts discharging motile
merozoites into the bloodstream
Merozoites invade the RBC and multiply within 48-72 hours
When parasites reach density of 50/ul in the blood, symptomatic
stage begin
P. vivax and ovale – portion of intrahepatic forms do not divide
immediately but remain dormant. This is the cause of relapses. The
dormant form is called hypnozoites
Merozoites enter the RBC and become trophozoites.
P. vivax receptor is Daffy group antigen Fya or Fyb.
West Africans have FyFy phenotype – makes it resistant to P. vivax
malaria.
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Page 2 of 9
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PLASMODIUM SPECIES
There are 4 major species that causes malaria:
1. P. falciparum
2. P. vivax
3. P. malariae
4. P. ovale
What are the common species of malaria parasites in the
Philippines?
o
Plasmodium falciparum and Plasmodium vivax are the
common species of malaria parasites in the Philippines
o
P. falciparum  60-70%
o
P. ovale  30-40%
There are also P. malariae cases and contributes to about <1% of the
total malaria cases.
P. falciparum malaria, if not treated immediately, can lead to severe
malaria, such as cerebral malaria.
P. vivax malaria does NOT lead to cerebral malaria but it causes
relapse if treatment was not completed.
P. falciparum – in the Philippines
P. ovale – in Africas
P. falciparum – in Asia
COMMUNICABLE DISEASES (IM)
Topic: Malaria
Lecture by: Dr. Fortuno
Plasmodium knowlesi
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Molecularly, entomologically, epidemiologically, data, indicate that
human infection with P. knowlesia is not newly emergent
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Primarily a zoonotic for reports of its emergence from monkeys
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Potentially fatal, but if detected early enough, infections in humans
are readily treatable
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Isolated from Philippine macques (maccaca fasciculus) in 1961
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Incriminated vector in Anopheles balabacerisis
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Published reports of human infection:
o
1965, 2004 – Malaysia
o
2004 – Thailand
o
2006 – China
o
2008 – Palawan (Philippines) ~2 cases
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Morphologically similar to P. falciparum and maybe mistake to be P.
falciparum
PCR is of value in diagnosis because P. knowlesi infection is easily
misdiagnosed as less dangerous
Plasmodium malariae infection with conventional microscopy
Notes from Old Trans:
P. falciparum:
 Has the shortest/ fastest hepatic phase; less than a week
 Has the biggest release per hepatocyte
 Attacks ALL type of RBC
P. malariae:
 Has the longest duration of erythrocytic stage.
 Attack senescent cells (reason why it is benign  senescent cells
will die anyway)
P. falciparum and P. knowlesi
 Species that have ring forms (reason why some P. knowlesi cases
are are mistaken as P. falciparum)
P. vivax and ovale
 Schuffer’s dots – the hypnozoital forms – the cause for the
relapse of infection because duration in intrahepatic can be very
long
Incubation Period:
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P. falciparum (12 days)
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P. vivax (14 days)
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P. malariae (30 days)
PARTS OF THE MOSQUITO
Clinical Presentation:

Morphologically similar to P. malariae or may be mistaken to be P.
falciparum because of abundant ring stages
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In Rhesus monkey studies
o
High parasite densities is possible
o
No significant sequestration in microcirculation
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In humans
o
Reported in children and relatively older adults
o
May present as mild form of malaria easily responding to
chloroquine but may also be severe and fatal
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Fever, headaches, intermittent chills, abdominal pain, sweating and
malaise
Characteristic
Duration of intra
– hepatic phase
Number of
merozoites
released per
infected
erythrocyte
Duration of
erythrocytic cycle
in hours
P. falciparum
P. vivax
P. ovale
P. malariae
5.5
8
9
15
30,000
10,000
15,000
15,000
48
RBC preference
Young but
can invade
all cell ages
Morphology
Ring forms,
banana
shaped
gametocytes
Pigment color
Black
Ability to cause
relapse
No
48
Reticulocytes
and cells up
to 2 weeks
old
Irregular
shaped large
rings and
trophozoites,
enlarged
RBC,
schuffner’s
dots
Yellow
brown
Yes
50
72
Reticulocytes
Older cells
Infected
eryhrocytes,
enlarged and
oval with
tufted ends,
schuffner’s
dots
Bands or
rectangular
forms of
trophozoites
Dark brown
Brown black
Yes
No
Lecture Discussion:
Proboscis  major structure of the mosquito head; mouthpart used for
sucking
Anopheles  also called the tiger mosquito of Asia; shares similar traits and
appearances with Aedes egypti; they are slender and has very long legs
Culex  usually found at home; stouter with shorter legs
Abdomen  it is where the sexual reproduction of the mosquito takes place
What is the difference between Anopheles & Aedes? Time of the day when
you were bitten
 Day biting  Aedes
 Night biting  Anopheles
Do all Mosquitoes carry the Malaria Parasite?
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No, not all mosquitoes carry the malaria parasite.
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In the country, it is the adult female Anopheles mosquito that can
become infective and therefore carries the malaria parasite after she
bites a person infected with malaria.
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The malaria parasite undergoes several developmental stages inside
the adult female mosquito until such time that the mosquito
becomes infective with malaria parasites.
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This anopheles mosquito bites from dusk to dawn (night biting) and
it breeds in clear, slow flowing streams that are found in
mountainous/forested areas or in brackish water where salt and
fresh water meet. This is usually found in coastal areas
*Highlighted in yellow were discussed by Dr. Fortuno
Can a person get malaria by drinking water in the streams with mosquito eggs?
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No it will not be possible. The malaria parasite has to undergo
development inside the adult female mosquito; therefore one cannot
get malaria from drinking water that has mosquito eggs in it. Another
is that the gastrointestinal acids will destroy the eggs immediately
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COMMUNICABLE DISEASES (IM)
Topic: Malaria
Lecture by: Dr. Fortuno
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Unstable Transmission:
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Erratic transmission
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Usually in hypoendemic areas
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Full protective immunity is not acquired
MOSQUITO VECTORS IN THE PHILIPPINES
Anopheles sp.
o
An. flavirostis
o
An. litoralis
o
An. maculatus
o
An. mangyanus
o
An. babacensis
Statistics:
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P. falciparum and P. vivax – responsible for most new infections
But because of the government’s effort to eradicate P.
falciparum, P. vivax is now having an emergence. There is now
more incidence of P. vivax than P. falciparum. But in terms of
prevalence  P. falciparum still is the highest
Lecture Discussion:
Anopheles is a picky kind of mosquito because it has to live in clean water 
they would not be able to live in urban areas due to contaminated water.
They thrive more in rural areas due to presence of cleaner water
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P. FALCIPARUM
RBC Changes:
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Once inside the cell, it consumes and degrades intracellular proteins
(hemoglobin).
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Alteration in RBC properties more irregular in shape and less
deformable. (less deformability)- disease the malleability
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P. falciparum – causes appearances of knobs on the cell surface.
o
Mediates attachment to the capillary and venular
endothelium (cytoadherence)  infected erythrocytes
stick inside and eventually block capillaries and venules
o
Rosette formation – infected RBCs may adhere to
uninfected RBC
o
Agglutination – infected RBC adhere to other parasitized
RBC
o
Cytoadherence, rosette, agglutination are central to the
pathogenesis of falciparum malaria, the result in the
sequestration of RBC containing mature forms of the
parasite in vital organs (esp. brain) where they interfere
with microcirculatory flow and metabolism
o
Sequestered parasites: splenic processing and filtration
 only the younger ring forms of the asexual parasites
are seen in the circulation
o
Other “benign” forms of malaria, sequestration does not
occur
o
Very toxic to erythrocytic  hemoglobin
o
P. falciuparum- change internal nuclear  degeade to Hb
to heme or hemosiderin
o
Falciparum prefer to survive in hemosiderin type
o
After invading RBC, malarial parasite degrade
hemoglobin and is converted to inert hemozin (malaria
pigment)
WHO ARE AT RISK OF GETTING MALARIA?
Children – because of immature immune system
Pregnant women – immunocompromised
Indigenous peoples
Forest workers, miners, soldiers
Persons who are not from a malaria endemic area but travel to this
area
Table Above:
This table shows which provinces have high cases of malaria: Encircled in red
are from Cagayan, Zambales, Rizal, Occidental Mindoro, Palawan, Davao
Del Norte, Sulu
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EPIDEMIOLOGY
Endemicity is defined as palpable spleen rates in children 2 – 9 years
old: (You do Abdominal Exam)
o
<10% - hypoendemic
o
11-50% - mesoendemic
o
51 – 75% - hyperendemic (e.g. Cagayan, Zambales, Rizal)
o
>75% - holoendemic (almost 100% has/had malaria)
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Africa and New Guinea
P. falciparum:
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Causes severe malaria.
Principal Determinants are:
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Biting habits
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Density of the mosquito population
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Longevity of the anopheline mosquito
o
The lifecycle that takes place inside the mosquito is
between 8 – 30 days.
o
Low temperatures are not conducive for sporogony to
take place
Stable Transmission:
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Constant year round transmission. (Infections can occur any time of the year)
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By adulthood would have achieved full immunity
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Creates a high level of parasitemia and sequestration causing end
organ damage.
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Sequestration is a specific property.
Sequestration only seen in falciparum. Sequestration  it is the
spleen trying to save the uninfected RBCs in the circulation. The
spleen will open up to get as much uninfected RBCs into its
parenchyma (saving them from being infected). But in the process
of sequestering the uninfected RBCs, what is left in the circulation
would be less RBCs (because the spleen has already sequestered
most uninfected RBCs)
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Usually seen in the smears are younger forms before sequestration
takes place.
COMMUNICABLE DISEASES (IM)
Topic: Malaria
Lecture by: Dr. Fortuno
Sequestration:
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Contribute to mental changes and coma.
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End organs affected are:
o
CNS, lungs and kidneys.
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A combination of all these results in:
o
Interference with microcirculatory circulation
metabolism especially in the brain
and
Other things noted in P. falciparum infection:
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Hypoglycemia
This is due to reduction of hepatocytes. Remember that
hepatocytes burst during the 1st phase of plasmodium infection.
And the hepatocytes are where gluconeogenesis and
glycogenesis take place.
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Lactic acidosis
When the RBC burst, it will release acid  contributing to lactic
acidosis
Picture Above: Symptoms of Malaria
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Severe anemia- CBC, ABG
Can be explained by the decrease in RBC volume, either caused
by destruction or sequestration of the spleen
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Multi - organ dysfunction secondary to hypoxia.
Usually occurs in travelers without immunity or young children living
in endemic areas.
You have a rapidly rising fever with severe headache. Just by looking at the
pattern of fever, you will already have an idea of what is causing it.
 If it is low-moderate grade (steady)  bacterial
 If it is high grade (spiking) – from 40-42oC  virus or parasite
There will also be paroxysms with shaking chills because the patient would
have some kind of dehydration already and hyponatremia.
There will be profuse sweating after the fever
Check for the spleen or liver  splenomegaly or hepatomegaly
There will also be myalgias (muscle pain) or orthostatic hypotension
Typical Manifestations in Diagnosing Malaria
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Severe anemia – usually associated with P. falciparum infections.
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May be secondary to RBC infection and a loss of infected RBC.
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Uninfected RBCs are inappropriately cleared and bone marrow
suppression may also be involved
Innate Immunity:

Depends on the host’s immunity.
If we have been exposed to plasmodium during our childhood
years it is possible. It is a hard earned immunity because you
either DIE as a child or SURVIVE as an adult from it
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Renal Failure:
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Infected RBCs adhere to the microvasculature in the renal cortex.
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Oliguric renal failure  ↓ blood sugar
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Usually reversible.
Especially when patient is subjected to immediate dialysis
P. falciparum usually results in death.
Protective Genetic Factors:
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Sickle cell disease
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Hemoglobinopathies
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Polymorphisms in the host’s Tumor Necrosis Factor (TNF).
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CLINICAL MANIFESTATIONS
Get a history of recent travel in those patients with high grade fever.
Most patients will present with fever and (generalized) headache.
o
There is no neck stiffness or photophobia resembling
meningitis.
Check for nuchal rigidity to rule out meningitis
Malaria free areas:
o
Aklan, Albay, Batangas, Benguet, Biliran, Bohol, Camiguin,
Capiz, Catandauanes, Cavite, Cebu, Eastern Samar,
Guimaras, Ilo-Ilo, Leyte, Marinduque, Masbate, Northern
Samar, Siquijor, Sorsogon, Southern Leyte, Surigao del
Norte, Western Samar
Malaria areas in and near NCR: Fairview, Antipolo
Malaria is a febrile illness characterized by fever and related
symptoms.
However, it is very important to remember that malaria is not a
simple disease of fever, chills and rigors.
In fact, in a malaria prone area, it can present with such varied and
dramatic manifestations that malaria may have to be considered as
a differential diagnosis for almost all the clinical problems.
Malaria is a great imitator and trickster, particularly in areas where
it is endemic.
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P. malariae can cause the nephrotic syndrome  ↓ albumin levels
Respiratory Symptoms:
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Metabolic acidosis leading to respiratory distress.
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Can develop pulmonary edema
Due to decrease in the oxygen content going to the lungs, the lung
would expand  pulmonary edema
Cerebral Malaria (CNS):

Cerebral malaria – almost always due to P. falciparum infections.
o
Coma lasts more than 30 minutes.
o
Fever (febrile)  seizure  coma cascade
Page 5 of 9
The brain needs to be highly perfused with blood and glucose.
Plasmodium destroy the hepatocytes  ↓ in glycogen storage 
patient may become hypoglycemic  brain can go on coma (due
to less perfusion & glucose)
COMMUNICABLE DISEASES (IM)
Topic: Malaria
Lecture by: Dr. Fortuno
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P. VIVAX & P. OVALE
Patient may relapse after long periods because of the hypnozoite
stage in the liver.
Can remain dormant for months to years before entering the blood
stream to produce symptoms.
Causes the benign form of tertian fever  P. vivax & ovale
o
(P. malariae causes the quartan fever)
Quartan fever means fever on the 1st and 2nd day but
no fever on 3rd day
o
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P. falciparum  no pattern of fever
PHYSICAL EXAMINATION
Most patients will have splenomegaly.
Test for:
o
CBC
o
Anemia
o
Thrombocytopenia
o
MARF - adult tubular necrosis secondary to hypovolemia,
ischemia, intravascular coagulation
o
Parameters:
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<1 ml/kg/hr.
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Elevated creatinine
DIAGNOSTIC PROCEDURE
Since Charles Laveran first visualized the malaria parasite in blood in
1880, the main-stay of malaria diagnosis has been the microscopic
examination of blood
Malarial Smear:
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In this procedure, a film of blood is placed on a slide, stained, and
examined microscopically.
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Peripheral smear examination for malarial parasite is the goldstandard in confirming the diagnosis of malaria
Demonstration of the Parasite

Must identify the asexual forms in the peripheral blood smear.

Negative smears DO NOT rule out malaria if there is a high degree of
suspicion. Repeat.  parasite may be residing in the RBCs or in the
liver cells
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Use the Giemsa stains at pH – 7.2
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Thick blood smear provides better sensitivity.

Thin blood smear provides better specificity and allows better
identification of the species involved.

Not so diagnostic in P. falciparum infections since sequestration
removes the RBCs out of the peripheral circulation especially in the
late stages.
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Hypnozoital (vivax and ovale)
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Diagnosis: visualization of blood smear
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Thick and thin smears done 12 to 24 hours apart during the fever
The fever pattern of P. falciparum is never regular  you will
never know when the height of the fever. Before, blood collection
is at the peak of fever. Now we do the think & thin smear at any
time the patient is febrile
THICK SMEAR
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More sensitive than thin smears.
Can’t identify the species
Parasitemia can be calculated
based on the number of infected
RBC.
Quantitative test.
Can concentrate the parasites
increasing diagnostic sensitivity
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Alternative Tests:
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Quantitative buffy coat – as sensitive as a thick smear but must still
do a thin smear.
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(PfHRP2) Histidine rich protein- 2 (the only approved rapid test in
the US.
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Rapid Diagnostic Test (RDT):
o
This is a blood test for malaria. It can be conducted
outside the laboratory and inside the field.
o
It gives a result within 10 to 15 minutes.
o
This is done to detect malarial parasite antigen in the
blood.
However, it does not detect whether the malarial infection
is active or not. It also will not detect the specific kind of
specie in the patient’s blood. It will only show if the patient
HAD or currently HAVE malaria
Additional Information from Old Trans:

Diagnosis of malaria rests on the demonstration of asexual forms of
the parasite in stained peripheral blood smears

Giemsa stain
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Thick film has advantage of concentrating the parasites and thus
increasing diagnostic sensitivity

Both parasites and WBC are counted and the number of parasites per
unit volume is calculated from the total leukocyte count

Before a thick smear is judged as negative, 100-200 fields should be
examined under oil immersion
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In high transmission areas, the presence up to 10,000 parasites/ul
maybe tolerated without symptoms or signs in partially immune
individuals
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Rapid simple sensitive and specific antibody based diagnostic stick
detect falciparum specific histidine rich protein 2 (pfHRP2) or lactate
dehydrogenase antigen

Some of the rapid diagnostic test carry a second antibody which
falciparum malaria to be distinguished from the less dangerous
malaria.

PfHRP2 maybe positive for several weeks after acute infection,
disadvantage in high transmission areas but is of value in the
diagnosis of severe malaria in patients who have taken antimalarial
drugs and cleared peripheral parasitemia

In general, >105 per ul is at risk of dying but non immune patients
may die with much lower counts and partially immune patients may
tolerate higher parasitemia levels

In severe malaria, poor prognosis is indicated by presence of
dominance of more mature P. falciparum (>20% of parasites with
visible pigment) in the peripheral blood smear or by the presence of
phagocytosed malarial pigment in >5% of neutrophils
THIN SMEAR
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Less sensitive.
Facilitate speciation
Qualitative test
Page 6 of 9
COMMUNICABLE DISEASES (IM)
Topic: Malaria
Lecture by: Dr. Fortuno
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MALARIA SUSPECT
Patients with malaria like illness
With thrombocytopenia
Relative lymphocytopenia
Atypical lymphocytes
Elevated LDH
Anemia
Multidrug Resistant P. falciparum & Treatment Failure

Ability of the parasite to survive and or multiply despite the
administration and absorption of a drug given in the recommended
or higher dose but within the limits of tolerance of the patient.

Basis:
o
Recrudescence of asexual parasitemia from 48 hours
after treatment
If in the 2nd day the patient has still parasites in the
blood despite maximum treatment  treatment
failure
OBJECTIVES FOR TREATMENT
Treat the malaria
Prevent development and spread of antimalarial drug resistance
3 medical conditions associated with Plasmodium infection:
1. Uncomplicated
2. Treatment failure
3. Severe malaria
Uncomplicated Malaria

Febrile

Parasites in blood

Absence of severe malaria and multi drug resistant P. falciparum

Severe headache, chills

Thrombocytopenia

For P. falciparum & vivax
o
Day 0 – 2  Co-Artem (Lumefantrine + Artemisinine)

Given after high fat meals

Contraindicated in pregnancy and lactation
o
Day 3  Primaquine

falciparum – gametocidal

vivax – hypnozoiticidal

Discharged if asexual forms are not seen in
Day 7 then monitor once a week for a month.
How to Assess:
Day 0, 3,7  do blood smear, if parasite not seen in day 7 it means
the patient is getting well. If still present, label as treatment
failure
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Other Plasmodium parasites and mixed infections:
o
P. malariae  Chloroquine
Primaquine
Page 7 of 9
o

No parasite clearance or reduction
Despite of management of Co-Artem and Primaquine,
on the 7th day the parasites are still there 
treatment failure
Objectives:
o
Cure the infection
o
Prevent the development of severe malaria
o
Prevent spread of drug resistant forms of the parasite
Severe Malaria

Dysfunction of organ systems secondary to:
o
Effects of malaria toxins
o
Sequestration of infected RBC
o
Anemia

Abnormal organ function tests

Jaundice

Hyperparasitemia (>2% parasitized RBC)

Severe anemia

Metabolic abnormalities

Hemoglobinuria
COMMUNICABLE DISEASES (IM)
Topic: Malaria
Lecture by: Dr. Fortuno
o
Severe malaria continued…..

Conditions of a person with severe malaria:
o
Seizures
Due to brain hypoxygenation & hypoglycemia
o
o
o
o
o
o

o
Artemisinin

Approved in 2009.

Cannot be used as monotherapy because of a high rate of resistance.

Due to only a temporary stop in the growth of ring stage parasites
(dormant forms) after exposure to artemisinin.
Impaired consciousness
Prostration/ weakness
Poor urine output
Signs of pulmonary edema
Signs of DIC – already going into sepsis  septic shock
Abnormal spontaneous bleeding
Chloroquine Phosphate

Can be used for prophylaxis and treatment.

Drug of choice for chloroquine sensitive malaria.
Treatment of Severe Malaria:
o
US FDA and WHO: Artesunate IV
o
DOH: may give Co-Artem

Quinine IV or Artesunate IV plus treatment:
Quinine or artesunate + tetracycline +
clindamycin
Quinine



Note: Tetracycline is not available in the market today due to its
notorious side effect of yellowish discoloration of teeth
(especially in children)
So in severe malaria we give: Co-Artem + Quinine/Artesunate +
Clindamycin

Mefloquine

Use of mefloquine for pregnant women in the second and third
trimester is sanctioned by the WHO and the CDC allow the use of
mefloquine even in the first trimester of pregnancy.
Day 0 – 2  Chloroquine
o
No treatment failure reported yet
Days 3 – 17  Primaquine
Treatment Failure

Falciparum malaria - Quinine and any of the three drugs:
doxycycline, tetracycline, clindamycin (QUININE PLUS)

Vivax – Co-Artem
o
If hypnozoites are suspected and fever recurs after 2
weeks Primaquine
Primaquine

Prevents drug resistant falciparum and vivax malaria in adults

Contraindicated in pregnant patients or new born babies

(x) G6PD deficiency  hemolysis  death
Treatment Under Special Conditions

Pregnant women:
o
Falciparum – oral quinine

Insulin secreting drug  monitor blood sugar
levels

Do not give Co-Artem
o
Vivax - chloroquine




TREATMENT
P. falciparum – resistant to chloroquine.
P. vivax – not so resistant to chloroquine.
P. ovale and P. malariae – sensitive to chloroquine.
Primaquine - needed to treat the hypnozoites (liver phase).
Artesunate

IV anti – malarial now used in the US for severe complicated malaria.

Reduced mortality among children in African countries compared
with quinine.

Patients have less symptoms of coma, seizures, post – treatment
hypoglycemia.

Water soluble derivative from artemisinin.

Drug of choice for severe falciparum malaria.

Recommendations for malaria treatment:
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No role in prophylaxis
Used with second agent in drug – resistant falciparum infections.
Used in pregnant women
Fansidar

Pyrimethamine –sulfadoxine.

Can also be used for treatment .

Not anymore considered as a first line drug for prophylaxis because
of adverse drug reactions.
Falciparum + either vivax or malariae

Co-Artem (falciparum) and Primaquine (vivax)
P. vivax

P. falciparum malaria: Quinine plus doxycycline or
clindamycin or pyrimethamine – sulfadoxine.
Alternative treatment: Artemether – lumefantrine, or
mefloquine
Page 8 of 9




SUPPORTIVE MANAGEMENT
Cerebral malaria
o
Unarousable coma not attributed to any other cause and
persists for > 30 minutes after a seizure
o
Treatment: fluid balance, hyperpyexia, control seizures
o
No mannitol, osmotic diuretics, steroids
o
Put ice bag on the head (brain cannot be subject to ↑
temperature)
Pulmonary edema
o
Increased pulmonary capillary permeability
Hypoglycemia
Circulatory collapse/ shock:
o
Do not give dopamine, dobutamine, epinephrine
o
Give norepinephrine (dilate BV without affecting the
patient’s heart)
COMMUNICABLE DISEASES (IM)
Topic: Malaria
Lecture by: Dr. Fortuno



BASIS FOR CHEMOPROPHYLAXIS
Each species has a specific incubation period.
P. falciparum infection typically develops within a month of
exposure. Rare cases have been reported up to a year later.
Hypnozoite form – P. vivax and P. ovale.
o
Parasite stays in the liver for months before inducing initial
infection.






Chemoprophylaxis:

Doxycycline 100 mg daily for 2 – 3 days before going to an endemic
area, continue while in the endemic area and continue for 4 more
weeks after leaving the endemic area

Lecture Discussion:
Why do you have to take it for 1 more month (4 weeks) even if you already
left the endemic area? It’s because you might have harbored the hypnozoites
in the endemic area  we are trying to kill it so you have to take it for 1 more
month


PERSONAL PROTECTION
Reduce the frequency of mosquito bites.
o
Avoid the mosquito’s peak feeding hours.
o
DEET containing lotions (e.g., off lotion) and picaridin
DEET has no teratogenic effect  safe for pregnants
o
Insecticide impregnated mosquito nets.



PREVENTION AND CONTROL
Malaria case should be reported.
A thorough screening of all infected person’s from mosquitoes is
important.
Mosquito breeding places must be destroyed.
Homes should be sprayed with effective insecticides which have
residual actions on the wall.
Mosquito nets should be used especially when in infected areas.
Insecticide Treated Bed Nets (ITN’s) have emerged as a very
important tool in malaria control in endemic areas.
Insect repellents must be applied to the exposed portion of the body.
o
Permethrin
o
DEET (N,N-diethyl-m-toluamide)
o
IR3535 (3-[N-acetyl-N-butyl]-aminopropionic acid ethyl
ester)
o
Bayrepel
(1-piperidinecarboxylic
acid,
2-(2hydroxyethyl)-, 1-methylpropylester)
Blood donors should be properly screened.
MALARIA SITUATION IN THE PHILIPPINES
Malaria is a rural disease
one of the important mosquito-borne diseases affecting far-flung
barangays of the country
Out of the 79 provinces nationwide, 57 are malaria endemic
Malaria Control Program:

Vision: malaria-free Philippines by 2020
Strategies:
1. Early diagnosis and prompt treatment
2. Vector control – insecticide-treated mosquito net as main vector
control strategy, complemented by indoor residual spraying
3. Early management and disease surveillance
4. Monitoring and evaluation
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Page 9 of 9