MALARIA Dr.
Diaz
Causes infection to human
Classified under Phylum Sporozoa
Intracellular obligate organism cannot survive without
the host cell
Undergoes a different process of multiplication:
Sexual process termed as sporogony whereby
its end product is called sporozoites (resulting
organism undergoing sporogony cycle)
Gametocytogenesis not necessarily
sexual or asexual
- An extension of asexual
process whereby one of the
product is gametocytes
(immature sex cells of the
organism)
- Gametocytes become the
starting point of sexual
process
Asexual process termed as schizogony
whereby the end product is called merozoites
(daughter organism after undergoing
schizogony)
Sporozoites is the starting point of
schizogony
Sporozoa parasite is subdivided into two big groups:
Coccidia
Otherwise known as Eimerina
parasites
Not necessarily popular and they come
to the surface when human beings
have discovered the immune system
When immune status of the human
was established, thats the time when
coccidian infection emerged such that
it becomes popular and important
particularly in AIDS
Not requiring insect vector for
transmission primarily ingested via
the oral groove
Both cycle (schizogony and sporogony)
occurs in a single host such that if a
person is infected with coccidia,
schizogony and sporogony will occur
inside that persons body
1 Jcelimpin 2C
Hemosporidia
Acquired thru the bites of blood
sucking insects primarily the
mosquitoes
Schizogony takes place inside the body
of the human beings human has its
asexual process
- Man serves as the
intermediate host
Sporogony (sexual process) takes place
inside the body of the insect
- Insect serves as the
definitive host
Hemosporidia: Genus Plasmodia
Only genus of human importance
Cause a disease called malaria
Most dangerous of animals under Kingdom Animalia
excluding human beings are from Genus Plasmodia carried
by mosquito that belongs to genus Anopheles which is
worst from accidents
More than 1 million of infants in Africa died of malaria
According to the prediction of WHO from year 2000
onwards, 65% of the world population were at risk of
having malaria while 45% was already infected since
1990s
Mosquitoes
Has resting or feeding position
They also have feeding time: some at night and some
during daytime
Those that feed at daytime are called day biting
mosquitoes
Those that feed at night are called night biters
E.g. Anopheles
o Before, night biters start sucking blood
at about six in the afternoon (6pm)
down to 4am in the morning
o Nowadays, they are looking daylight
saving time and they feed or suck
blood at about four in the afternoon
(4pm)
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4 Genre of mosquito causes infection and all with resting/ feeding Aedes
position

Anopheles only vector for plasmodia

Aedes popular for dengue specifically the A. aegypti

Mansonia

Culex
The posterior of the longitudinal axis is forming
an acute angle on the surface when it rest
Innate Characteristics of the Mosquito
Best breeding place is dirty stagnant water
The tip of its limb is a very sensitive structure for vibration
In the Philippines, dengue became in endemic in
Its foot pads is sensitive to vibration due to
places wherein there is dirty stagnant water
presence of sensor or nerve endings for motion
Anopheles
The tip of the proboscis (mouthpiece) is a very thermo
sensitive structure which can detect a difference of 0.5C
temperature

Blood determines the temperature of the body

thats why they are provided with thermo
sensitive structure

Able to locate the hottest point of the skin

wherein the capillary bed are present (human
body drives out heat from the capillary beds due Longitudinal axis going anterior is forming an
to its thin endothelium) acute angle on the surface when it rest
Mosquito sucks blood directly from the Breeding place is generally c slow running
capillaries cleaning water
Genus of Mosquito according to its feeding position: Malaria is acquired mostly at the mountainous
area wherein there is slow running clean water
Culex and Mansonia
(e.g. river, creeks)

Transmitter of the Hemosporidia

Night feeding mosquito

It has been studied that if the flow of water is

>20 km/hr its larva dies

Developmental stage of the mosquito:

Collectively known as Culescine egg larva (aquatic) pupa (aerial)

Almost parallel to the longitudinal axis If the speed or flow of water increase,
the larvae of the mosquito gets
Vases were the favorite sites plant vases with drowned and eventually died
clean water
*Aedes and Anopheles belongs to superior group

Vectors: more than 50 species serve as a vector for malaria

Anopheles flavirostris and Anopheles minimus common

vector all over the world

Anopheles mangyanus found in Mindoro

Anopheles balabacensis and Anopheles litorensis at the

southern part of the country

2 Jcelimpin 2C 01132012
 A. balabacensis is also present in Malaysia and Diseases
in almost Asian countries
Plasmodium falcifarum
Anopheles dirus present in Indonesia; not found in the
Philippines Malignant malaria producing a severe type of
infection by which patient can die
*mosquito cannot fly beyond 2 meters above the ground; they
only attached on clothes as we go to higher place Falciparum malaria

*the average lifespan of the mosquito is 1month Subtertian malaria when the manifestation is not
typical
Endemic places in the Philippines
Estivo-autumnal increases during the summer and
- Common places with malaria in the country cold days

Bicol region Plasmodium vivax

Mindoro region Vivax malaria

Palawan Benign tertian malaria can also be referred to ovale

infection
Sulu provinces (Sulu, Basilan, Tawi-tawi)
Plasmodium malariae
Malaria can be diagnosed thru blood film examination
(most simple way of diagnosing malaria infection) Quartan malaria least severe infection

Quezon City particularly Novaliches - The growth of organism is rather slow

Rizal particularly Antipolo and Montalban Epidemiology

Etiologic Agent causing Malaria Plasmodium vivax

Plasmodium falciparum The predominant form of malaria infection

Plasmodium vivax Very common species found anywhere in the

world
Plasmodium malariae
Majority of cases has vivax infection (particularly
Plasmodium ovale in the Philippines)

Dominance Malariae malaria

P. falcifarum is considered dominance against P. vivax common species is Plasmodium malariae

P. vivax is dominant against P. malariae
P. vivax and P. ovale oftentimes shared common
characteristics P. vivax characteristic is similar with
that of P. ovale except for epidemiologic distribution
Limited to the subtropics and temperate region
in the world
Part of the Philippines is subtropical hindi
masyadong mainit, hindi masyadong malamig

The dominance goes in if there are 2 organisms infecting a Quartan malaria produces the least severe
man e.g. P. falcifarum and P. vivax P. falciparum will form of infection growth of organism is the
suppress the growth of P. vivax most slow

Single species infection the dominant organism will Plasmodium ovale

suppress the recessive ones; common situation which is
explained because of dominance Found in tropics, subtropics and Asian countries
(referring Thailand) particularly African countries
Mixed infection having more than 1 organism as well as South America

Sequence: P. falciparum> P. vivax > P malariae - Asian countries Thailand, and Burma
(now! Myanmar)

3 Jcelimpin 2C 01132012
 Not very common but cause severe infection
Not present in the Philippines
Malaria parasite has sporogony and schizogony cycle
Schizogony of the human parasite occur in the human
body while sporogony occur inside the body of the
mosquito
****Note! Please refer to the diagram given by Dr. Diaz
Nos. 22a-31 refers to sporogony cycle or the sexual cycle
- In the book, it is also called extrinsic cycle (meaning
outside the human body) or an invertebrate phase
(refers to the mosquito having no backbone)
Nos. 1-20 thats going to be the schizogony cycle
Nos. 1-21 called the intrinsic cycle (inside the human
body) or a vertebrate phase
Nos. 20-21a/b is the production of gametocytes or sex
cells called gametocytogenesis
No.20 labeled as merozoites which is the end product of
schizogony
Nos. 6-20 refers to schizogony inside the red cells or
simply called it erythrocytic schizogony
Nos. 1-5 occurs outside the red cell or exoerythrocytic
schizogony or simply EES
The night biting female Anopheles mosquito is the vector
for malaria
The sporozoites which are the end product of sporogony
contained in the body of the mosquito are found at the
acini of their salivary gland
No.31 refers to the salivary gland of the mosquito
- The black object inside represents the sporozoites
that are contained at the acini of the salivary gland of
the mosquito
st
- Mosquito has a bad habit of spitting out 1 its saliva
before it sucks blood in our capillaries
- When the mosquito spits out saliva, it is injecting
sporozoites into the bloodstream directly into the
capillaries
- The sporozites outside the host will have a very short
lifespan (chance of survival) of not more than 30 mins
- Once injected inside the body of human, these
sporozoites will find another host cell within 30 mins
and that can do by finding the liver cell
4 Jcelimpin 2C
No.1 represents the cell of the liver (hepatocyte)
- The sporozoites can enter inside the hepatocyte
simply because the membrane of the liver has a
specific protein receptor for sporozoites
- The protein receptor at the membrane of the
hepatocyte is specific only for the protein contained
in sporozoites thereby these sporozoites are able to
go inside the cytoplasm of the hepatocyte
No.2 the organism is already inside the cytoplasm of
hepatocyte
- Malaria parasite is an incomplete cell because they
have no cell wall and no nucleus, the nucleus
counterpart consist only of chromatin material that
has the genetics of the organism. Its DNA is inside the
mass of chromatin material
- Since it has no nucleolus and nuclear membrane,
chromatin mass will be then called as chromatin
dot and its chromatin dot has cytoplasm with golgi
complex
- When it has a single chromatin dot with a strand of
cytoplasm, we call it as trophozoite stage or
specifically the hepatic trophozoite or
exoerythrocytic trophozoite because it is schizogony
occurring exoerythrocytic
- When the parasite is able to adjust inside the new
environment, it will feed on the content of the
hepatocyte and grows then undergoes asexual
reproduction which is simple binary fission that
happens by just splitting of the chromatin dot into
several numbers. Later, on the individual chromatin
dot will have its own piece of cytoplasm
No.2b is the organism undergoing binary fission or part
of the schizogony already. There are several chromatin dot
and we can call that the tissue schizont or hepatic
schizont (schizont stage). After becoming a schizont, it is
going to mature, when several chromatin dot has its own
cytoplasm already, each chromatin dot become a separate
organism or individual organism although contained in a
single host cell such as what is seen in no.3
No.3 is the mature hepatic schizont/ tissue schizont or
mature erythrocytic schizont where you have plenty of
organisms already. These organisms are going to adjust
and multiply further more. As the organism multiply, the
host cell enlarged and the membrane cannot limit it
indefinitely and soon going to break. When the membrane
ruptured (No.4), the individual merozoites will go out seen
in no.5
No.5 labeled as merozoites or the exoerythrocytic
merozoites.
- Other textbook says that these merozoites are going
to infect another hepatocyte. Due to genetic studies,
scientist discovered that merozoites coming from the
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 liver or elsewhere will not be able to infect
hepatocyte. The reason is that the surface membrane
of the hepatocyte does not have protein receptors for
merozoites, there is no specific receptor intended for
merozoites.
- Long time ago, they thought initially that merozoites
can infect another hepatocyte and then the parasite
st
is going to develop so much so that after 1 batch of
no.5, there will be succeeding batches of no.5 and
continuously infect the hepatocyte of the liver. But in
reality, hepatocyte will be infected once. Not unless
you are bitten by a mosquito every day, in that case
you will have another cycle in your liver cell.
- From no.1-5, on the average, it will take 14-21 days to
complete the process and that is called incubation
period or biologic incubation period wherein there is
no manifestation of sign and symptoms yet. During
that time, the organism is going to establish and
multiply inside the body of the person and not able to
produce disease.
- After several studies, they have found out that the
liver cell dont have the receptor that will adhere or
attached the merozoites on its surface so it is not
possible for the merozoites to invade hepatocytes.
Sporozoites is the only organism that can invade
hepatocyte which came from the mosquito (definitive
host)
- Where the other batch of the merozoites did came
st
from aside from the 1 one? These merozoites came
from 2a.
2a is the dormant trophozoites occurring only in two
species: P. vivax and P. ovale. We can specify them as
sleeping trophozoite but the technical term for that is
hypnozoites. These hypnozoites will remain dormant for
sometime on the average of 1 month. Then after, they are
incited to develop seen in diagram which is 2a-2b. It will
then mature and will eventually release merozoites which
became the other batch of merozoites.
st
- The 1 batch (no. 1-2-2b-3-4-5) is called primary
exoerythrocytic merozoites. In particular, P. vivax
and ovale (no. 1-2a-2b-3-4-5), this batch of
merozoites is called the secondary exoerythrocytic
merozoites. The importance of primary and
secondary exoeryhtrocytic merozoites is seen in a
clinical condition called relapse.
- In malaria infection, there is true relapse or otherwise
known as recurrence and recrudescence (not a true
relapse).
- True relapse there is a patient diagnosed with
malaria. You administer the drugs for treatment and
the person turned out to be negative for parasite and
you advise the patient not to be bitten by mosquito.
The patient followed preventive measures. But after a
month ago, signs and symptoms were manifested
again and you examined the patient and turned out
5 Jcelimpin 2C
to be positive in malaria. The source of infection
would be the hypnozoites or the secondary
exoerythrocytic merozoites. This condition is known
as recurrence occurring in P. vivax and ovale
- Recrudescence the patient is infected with P.
falciparum or malariae. After giving treatment and
being tested it turned to be negative but after some
time the patient was re infected again. It might have
been the treatment is not sufficient so much so that
organisms stucked up in tiny blood vessels develop
into mature ones. Reinfection is due to incomplete
treatment. This condition is known as recrudescence.
- In case of P. vivax and ovale, it could also be
incomplete treatment in a reason that you forgot to
give medication that will act on hypnozoites because
there is a particular drug for hypnozoites. In these
species, if there is reinfection, always think of
recurrence.
After merozoites are being release from the host cell, its
lifespan is about 30 minutes only so it has to find another
host cell. If the merozoite was not able to find another
host cell, it will disintegrate into the bloodstream. The
receptor protein for merozoites is found on the membrane
of RBC. So that means that merozoites will not be infecting
hepatocyte but rather go inside the RBC.
Plasmodium vivax and ovale prefer young RBC
- One month old RBC is considered young as well as
two month old RBC. Three to four month old RBC is
the one considered old. Every single time we have
young RBC in the circulation. If we have much young
RBC, P. vivax and ovale has greater chance of survival
due to several young RBC that will serve as a host
- need to sort young and mature red cell and then
choose the young one.
Plasmodium malariae prefer mature RBC
- Mature RBC of about 3-4 months old having lesser
population than the young ones.
- There is a greater chance that P. vivax has a more
severe infection as compared to malariae due to
availability of host red cell.
- Need to find mature red cell which is probably adhere
on the endothelium and not present in the circulation
and eventually disintegrate
- Has the least severe infection
Plasmodium falciparum prefer both young and mature
RBC
- There is no particular preference on the age and
maturity of red cell to be infected
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 - Has most likely to have the most severe infection
because of the availability of several host red cell. the
merozoites will not easily die because right away it is
able to infect rbc.
Joke time! hahaha
Plasmodium vivax Phedophile (mahilig sa bata)
Plasmodium malariae gold digger (mahilig sa
Miranda)
Plasmodium falciparum maniac (rapist: walang
pakialam kahit sino na lang)
As to severity of infection: (from greatest to least)
P. falciparum> P.vivax> P.malariae
Dominance and preference to the host red cell contributed
on why P. falciparum cause the most severe infection
These malaria parasite get their nourishment from the RBC
particularly hemoglobin. Protein as the most important
nourishment for living organism. The globin part of
hemoglobin will serve as the food or nourishment for the
organism while the heme part will become the waste
product. The parasite mainly used acid digestion of the
hemoglobin.
As the hemoglobin is digested it will split into heme and
globin. The globin will be utilized and the heme will
become the waste products and eventually became
malarial pigment. Acid digestion is the process of
degradation of hemoglobin. Therefore the resulting
product is not actually called hemozoin but rather
HEMATIN. Although it is acceptable to be called hemozoin
but it should be hematin.
In relation, our hemoglobin should be in normal condition.
When it became abnormal, malaria parasite will not be
able to survive inside the RBC because the organism was
not able to feed on it. For e.g. hemoglobin S (sickle cell
anemia) which offers relative resistance against malaria.
Another abnormality is thalassemia as well as hemoglobin
F (fetal hemoglobin) which is not the preference of malaria
parasite. Malaria parasite prefer hemoglobin A. G6PD has
also relative resistance against malaria infection they
can be infected, but it need to have plenty of sporozoites
No.6, 7, 8 the organism inside seems like ring and the
cytoplasm enlarged and not the no. of chromatin dot.
These are trophozoite stage which is characterized by a
single chromatin dot
No.9, 10, 11 undergone the process of binary fission and
now called schizonts stage
No.6 young trophozoites
No.7 growing trophozoite
6 Jcelimpin 2C
No.8 mature trophozoite the entire interior of the red
cell is filled up with the cytoplasm of the parasite. There is
a small vacuole near the chromatin dot. If there is no
vacuole, that organism may not be mature trophozoite.
When the chromatin dot splits into two, schizogony taking
place.
No. 9 young schizont. As soon as the chromatin dot splits
into two, it is now called young schizont not unless dealing
with P. falciparum. No pleomorphism exhibited. The
cytoplasm of each chromatin dot is separated to each
other
- In P. falciparum, the organism is so unusual that
it shows different forms. The chromatin dot can
be a comma, exclamation point, headset shape,
dot, etc. this kind of characteristic exhibited by
P. falciparum is called pleomorphism (a feature
of P. falciparum infected red cells. There can be
more than one organism which means that there
is multiple infections (most in P. falciparum,
lesser in P.vivax and ovale and least in P.
malariae). At any given time. There can be +1, +2
or +3 multiple infections in P. falciparum. For P.
malariae, it can be plus (+) or minus (-) .
- Multiple infection (allow more chances of
survival of the parasites)
P. falciparum> P. vivax and ovale> P.
malariae
No.10 growing schizont
No.11 mature schizont
- Each species has an exact no. of merozoites that
are able to produce.
P. vivax and ovale 12-24 merozoites
P. malariae 6-12 merozoites. With
least no. of merozoites produce.
P. falciparum has 18-24 and can be up
to 32 merozoites. With most no. of
merozoites produce.
No.12 rupture of red cells which expelled out
merozoites. So these merozoites will be infecting another
host red cell. In no.20 wherein the merozoites come out, it
also infects another host red cell. Therefore, it shows that
liver will just be infected ONCE and several times for the
red cell. Infecting red cell was continuous as long as the
person is alive.
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 From no.6-12 is one ES cycle already or one schizogony
producing its product which is the merozoites.
- Each species has time duration for ES cycle.
(Shortest to longest)
P.falciparum > P. vivax and ovale > P.
malariae
P. vivax and ovale exactly 48 hrs (2days)
Plasmodium malariae 72 hrs. longest ES
cycle
P. falciparum between 36-48 hrs. Shortest
ES cycle. Fastest in making daughter cells.
Factors considered why P. falciparum can cause the most
severe infection
Dominance
Host cell preference/ availability
Multiple infection
# of merozoites produce
Duration of ES cycle
Questions:
Can you have malaria other than the bite of mosquito?
Yes by means of blood transfusion.
In case of blood transfusion, are you going to have
hypnozoites?
No, because only mosquito can produce sporozoites
wherein the hypnozoites originate.
In blood transfusion, what stage of the parasite is
acquired?
Merozoites which came from the RBC
Are you transfusing the actual merozoites?
No, because the merozoites has 30 minutes lifespan only
outside the red cell. You only transfused the red cell which
is infected. The red cell being transfused has the young
trophozoites already. If it is P. vivax, after 2 days the red
cell will rupture and then eventually infect another red
cell. So the infective stage in blood transfusion is the
erythrocytic merozoites.
It is possible to transmit malaria via the placenta?
No, malaria cannot enter to the mothers womb going to
the fetus due to presence of placental barrier. However,
whenever a mother gave birth, the umbilical cord as well
as the placenta is retracted which then create a space in
7 Jcelimpin 2C
between and there will be a tear. So the placental barrier
will be denuded making it open the infected red cell from
the mother will then gain access to the umbilicus and
infect the fetus.
During admixture of maternal and fetal blood, malaria
parasite will then be transferred. But strictly speaking,
there is NO CONGENITAL MALARIA. It should be called co-
natal infection. If it is congenital, the baby should not be
the delivered yet. In co-natal infection, the baby is already
delivered but the umbilicus is not yet separated or cut.
Transfer of parasite occurs at the last trimester of
pregnancy.
If this is P.vivax, from no.6-20, how many hours
do it takes to complete the cycle?
96 hours or 4days
There should be 2 or more ES cycle before 20a /b and 21
will have to occur. This process is called
gametocytogenesis. From the time you have bitten by P.
vivax, until you have gametocytes is approximately 18days
(2 weeks + 4).
Without having any reason, some of the no. 20 will not
become no.6 anymore. Some others will become no.6
then no.20a/b and then the rest become 21a/b.
No. 21a is macrogametocytes (female) wherein its
chromatin is a solid mass situated at the periphery of the
cell while 21b is microgametocytes (male) wherein its
chromatin is granular situated at the center of the cell.
These stages remain dormant in the circulation. While the
cycle is going on dormant gametocytes and merozoites
keep on increasing. The gametocytes will not further
develop inside the human body; it only remains in
dormant stage. Merozoite is the one that develops.
While the merozoites coming from the no. 19, the no.20
erythrocytic merozoites will keep on infecting the red
blood cells as it goes to its cycle increasing in no.,
increasing infected red cells and also increasing
gametocytes as one cycle is finished. They are all
accumulated inside the body of infected individual.
When the mosquito comes along and feed on the infected
persons blood, the mosquito is going to sucked up the
gametocytes. So the mosquito gets infected by means of
sucking the gametocytes while the human gets infected by
means of sporozoites.
The gametocytes that goes in into the gut of the mosquito.
Inside the gut, the macrogametocyte and
microgametocyte will undergo another process of
development. The macrogametocye is undergoing
maturation where in the chromatin mass is going to the
most periphery of the host cell and it is going to grow a
pole and that is a mature sex cell already and called
macrogamete seen in 22a. On the other side is the
microgametocyte, the chromatin inside the host cell will
migrate towards the peripheral portion. Each of it will
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 have 6-12 chromatin moving into the peripheral side
(generally all species has 6-12) and each one of this will
grow a tail or flagellum and that is called the microgamete
seen in 22b. One of the flagellum of microgamete will
detach and try to find the pole of macrogamete. this
flagellum of microgamete will go inside the macrogamete
seen in no.23 to join to its chromatin so fertilization is
already taking place because there union already of the
sex cells.
No.24 zygote which is the product of union of sex cells.
The zygote later on will become amoeboid seen in no.25.
The amoeboid organism called ookinete. Because of its
amoeboid ability can move inside the gut of the mosquito
and it will try to find a weak point between the columnar
cells at the lining of the gut. The ookinete is trying to push
the wall inside the gut of the mosquito seen in no.26. The
outer coat of the gut upon entry of organism will now
become cyst wall then it will become a cyst having the
organism inside.
No.27 is an immature oocyst which then becomes oocyst.
No.28 is when the organism undergone binary fission and
produce a spindle shaped organism. Each one of it having
chromatin and labeled as the sporocyst (cyst containing
sporozoites). Sporozoites inside will result to the rupture
of the sporocyst.
No.29 is the ruptured sporocyts releasing the no.30 which
is the sporocyst and cycle is now complete.
Pathogenesis of Malaria
In P.vivax, it will take 2 days (48 hrs) for it complete the
cycle in no.6-12. Normally, the life span of RBC is 120 so in
this case the red cell will be destroyed earlier. There is
going to be destruction of the red blood cells. In this case
12-24 parasites will be produce in 2 days seen in no.6. So
as the days passed by, more and more organisms will be
produced so multiplication of organism is faster.
In P. falciparum, in 36 hours, 18-24 organisms will be
produced. When accompanied by multiple infections
there will be also more and more organism. The basic
point here is the red blood cells are being destroyed
earlier than it should by the exoerythrocytic merozoites.
When more and more RBC is destroyed earlier than it
should be, there would be anemia.
The pathogenic form of malaria is erythrocytic
merozoites. These organisms keep on destroying red
blood cells continuously.
Anemia is most severe in P. falciparum because more and
more RBC are being destroyed and infected because it has
no specific preference of RBCs maturity or age. It can
infect and destroy either the young or mature RBC. Also
due to possibility of multiple infection and short duration
in completion of cycle. P. malaria has the least severe form
of anemia.
8 Jcelimpin 2C
Iron deficiency anemia in malaria is not only due to
destruction RBC earlier than it should. Normally, there
would be sequestration of RBC in the spleen. When the
RBC is being destroyed, it will be sequestered and then
rupture and eventually hemoglobin will be released. The
heme and the globin separate. Iron from the heme will
now go to the bone marrow for recycling.
In case of malaria, the iron from the RBC will not be
recycled anymore but rather, will be used by the parasite
for nourishment. Upon degradation of hemoglobin, the
globin will be used for food and the heme will become a
pigment. The pigment is not giving free iron anymore. For
the iron to reach the bone marrow it has to be liberated or
free iron. There will be no free iron anymore because iron
is now bound to hematin pigment already and so there will
be iron depletion.
Massive destruction of red cells is expected to happen in
case of P. falciparum infection and therefore there will
rapid depletion of iron stores.
Anemia is not only due to destruction of red cells but also
due to depletion of iron due to utilization of parasites.
Normal shape of RBC is biconcave disk. When parasite is
contained inside it, it will bulge and become round in
shape. When the spleen sensed that RBC has an abnormal
shape, it will be destroyed.
When there is plenty of abnormal shape of red cells, it will
now be passing the splenic sinusoids and will be
destroyed. In that case, the spleen has plenty of work to
do and undergo histological event called hyperplasia
(happen in a labile organ like the spleen) which is an
increase in the no. of cells. When there is an increase in
the no. of cell, the spleen will enlarged and that condition
is called splenomegaly.
Massive hyperplasia will lead to hypersplenism which is
characterized by too much enlargement of spleen and too
much reactivity of it in a sense that destroys plenty of cells
even the normal red cells. There will be compression of
sinusoids and therere the organ will be compress. The
capsule will not allow enlargement of spleen indefinitely,
there is also a certain limit to it. Due to compression of
cells, the sinusoid will narrowed and permit the damage of
the red cells through rupture so cells even the normal are
being destroyed.
Massive splenomegaly can happen in malaria infection.
When the RBC is destroyed earlier, aside from being
infected, the normal cells are also destroyed then we
develop more destruction of RBC and more severe form of
anemia. The hemoglobin released from the RBC will now
be excreted via the urine creating hemoglobinuria
characterized by tea-colored urine.
Since there is massive infection and destruction of RBC
especially in P. falciparum, there would be black water
fever.
01132012
 Liver will also be affected leading to hepatomegaly due to
enlarged spleen. When the spleen enlarged, there is
damping back of blood into the liver, there would be an
alteration in blood flow and eventually lead to liver
congestion.
Another manifestation of malaria is fever. All kind of
infection may cause fever except dermatophytes infection.
The parasite is inside the red cell, when it cause rupture of
RBC, waste product will be released and served as
pyrogen. The pyrogen will go to the hypothalamus and
setting the thermostat of the body into higher
temperature although usually, it doesnt go beyond 40C
not a toxic fever).
Malarial paroxysm is the periodic occurrence of the fever
in case of malaria infection. In P. vivax, fever will be
expected every 48 hours, 72 hours in P. malaria and 36-48
hours for P. falciparum.
Tertian malaria for P. vivax occurring in 3days. Since P.
falciparum causes most severe infection it is called
malignant tertian. P.vivax causes benign tertian malaria
since it causes less severe infection in comparison with P.
falciparum. 72 hours is the time allotted for P. malariae
occurring in 4 days according to the chart and is called
quartan malaria. In P.falciparum, fever occurs less than 4
days so it is called sub tertian malaria.
st
Fever occurrence of malaria is quite nice, 1 he patient will
feel be very cold and chills develop leading to shivering
and eventually followed by fever and later on theres
going to be sweating
Typical malarial paroxysm
Fever
Chills
Sweating
Typical malarial paroxysm is observed in the following
conditions:
During the earlier stage of infection, the
infected red cell are not yet much and the
ruptured red cell is not yet enough or sufficient.
Pyrogen produced was very little. There can be
fever, there can be not. The development of
parasites are not yet synchronized or
established.
In the presence of P. falciparum infection,
irregular paroxysm is expected which can
develop at any given time and unable to predict.
9 Jcelimpin 2C
Unlike P. vivax and ovale, there is exact time
(exactly every 48 hrs).
- The organism is said to have ESTABLISHED
infection when it already made 2 or more cycles
and gametocytes are already present in the
circulation. If there are no gametocytes, it means
that the infection is only at earlier stage.
If there is mixed infection, irregular fever will be
expected. For e.g. the patient is being infected
by P. vivax and malariae so the patient will be
expecting to have fever every 48 hrs and every
72 hrs. respectively. So there will be overlapping
of the cycle.
Factors to be considered in typical malarial paroxysm:
Early stage of infection
Presence of P. falciparum
Presence of mixed infection
Four Major Manifestations of Malaria:
Anemia
Splenomegaly
Hepatomegaly
Fever
SPLENOMEGALY - is the consistent manifestation that is present in
all cases of malaria
It is not hepatomegaly because splenomegaly should occur
st
1 before it happens.
It is also not anemia. If there is little infection, anemia will
not be manifested specifically in P. malariae.
If the spleen enlarged too much, the very dangerous event
that could happen is spontaneous rupture and the patient
can die due to massive internal hemorrhage.
To confirm that you are palpating the spleen and not the
kidney, you will palpate the splenic notch at the left upper
quadrant of the abdomen. Normally, spleen is not
palpated because it is located retroperitoneal and
underneath the diaphragm. The shape of the spleen is
likened to the artists palette.
Even the patient is in sub clinical condition; there is
splenomegaly because the spleen is able to sense the
abnormal RBC (presence of organism).
01132012
The pathogenesis of malaria is the presence of malaria inside the red
cells (starting point)
One pathway is causing destruction of RBC and depletion
of iron producing anemia
Another pathway is abnormality in the shape of RBC as
being sense by the spleen will undergo hypersplenism
destroying RBC including the normal RBC
The other mechanism is infection of P. falciparum creating
knob formation on the RBC, making it to be foreign
already to the blood vessel of the human body. When it is
foreign, it is attracted to the endothelial wall of the blood
vessels. So when the RBC becomes foreign in the
circulation, it will come into contact with the endothelial
wall and stimulate the coagulation pathway. Upon
activation of the pathways, the platelet and RBC packed up
in particular area (adherence of abnormal RBC) creating a
microthrombi inside the capillaries. The infected RBC will
become adherent to the endothelial wall of the capillaries
primarily of internal organs.
Microthrombi led to impedance or hindrance of the blood
flow because it will block the blood flow. When it does,
there will be diminution of blood supply to the end organ.
Diminished blood supply to the organ diminished iron
content to the blood. Destruction of the RBC will result to
cellular/tissue anoxia/hypoxia/ischemia in malaria.
The main pathogenetic event in malaria is cellular anoxia/
hypoxia and not anemia.
Sites of the human body devoid of blood supply
Cornea
Hair
Nails
Malaria is affecting every human cell in the body. All cells
are affected because all have blood vessels. There is
depletion of oxygen carrying capacity of the blood due to:
Anemia depletion of iron
Massive RBC destruction
Impedance of blood flow d/t microthrombi
In P. falciparum infection, there is knob formation. If there
is significant no. of RBC being infected accompanied by
knob formation, all of them are foreign into the
endothelium, so all endothelial walls can be adhered by
these infected RBC leading to disseminated formation of
microthrombi. When it happens, there will be
consumption of coagulation factors, the condition known
as consumption coagulopathy. In this case, the patient
may develop spontaneous bleeding.
DIC is also synonymous to consumption coagulopathy
wherein all fibrinogen are being used up. In case of DIC,
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the most very dangerous that is going to happen is sepsis.
That is adding more insult to the injury and results to
septic shock (shock due to the microcirculation
disturbance)
Diagnosis
1. History and Physical Examination
The risk or having the chance of infection (bite of
Anopheles mosquito)
Blood transfusion (minor part), because malaria can be
acquired thru this the cut off period for blood
transfusion malaria is 6 months. Incubation for malaria is
one month generally. Manifestations are seen one month
onwards.
In PE (not giving much pathognomonic manifestation), you
will only see non-specific manifestations such as:
Anemia
Hepatomegaly
Splenomegaly
Fever
- All of them are non specific, unless there is
typical paroxysm. Splenomegaly even it is the
most consistent manifestation in malaria, it can
also be seen in other diseases like blood
dyscrasia, typhoid fever and other diseases.
2. Blood film examination
The most diagnostic way of doing the investigation
It is the blood wherein we are able to if infection exist
Blood samples can be collected anytime of the day
schizonts is much easier to identify because it has
increases in size already and has 2 chromatin dot already
Before the paroxysm or rise of fever, the stages seen are
the schizonts because they are about to rupture a little bit
later and it is much easier to identify compare to the
trophozoites
The best time to get blood sample is prior or before the
expected rise of the fever.
After the fever, the stages present in the RBC are
trophozoites which are difficult to identify.
At the height or peak of the fever, the stages seen inside
RBC is NONE because there will be no fever unless the cell
is ruptured. Inside the RBC, you dont see anything at the
height of the fever. Because the merozoites are located
outside the RBC for about 30 minutes. Beyond 30 minutes,
merozoites died.
01132012
 Degree of Infection
I. Relative count
A. Thin smear counting 1,000 RBC. All cells are seen.
% infection = # of infected cells X 100
1000 RBC
B. Thick smear RBC is not seen already because it has
been destroyed. WBC, platelets and parasites are only
seen
% infection = # of actual parasites X 100
100 WBC
II. Absolute count higher degree of accuracy are attained
- Will give the no. of red cells infected per cu.mm.
% infection X RBC count = __/Lx10
Usual degree of infection among species is as follows:
P. falciparum 150,000 500,000 red cell/cu.mm
- With highest degree of infection
P. vivax and ovale 50,000-100,000 red cell/cu.mm
P. malariae 50,000 red cell/cu.mm
- The usual degree of infection will able us to see
those resistant cases because there are already
resistant forms practically P. falciparum with
chloroquine (for treatment of malaria)
Malaria can produce several complications owing to have
the tissue anoxia.
Complications in Malaria
1. Cerebral form of malaria
It is when the tissue anoxia is affecting much area of
the brain so much so that if severely infected can
undergo coma not because of other cause but due to
brain involvement
Manifested and may end up with seizure
Headache which become the constant/ common
complaint
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2. Severe anemia
Expected in P. falciparum
It is not only the infected RBC that will undergo lysis
but also the normal RBC that will result to further
injury (hypersplenism)
There is massive intravascular hemolysis more
profound anemia
3. Black water fever
Also signifying massive hemolysis
4. Renal disease
Too much hemoglobin (massive hemoglobinuria) can
destroy the tubules of the kidney producing acute
tubular necrosis
Among the species, the least capacity to produce
merozoites is P. malariae and it takes a long time to
complete the cycle so there is a tendency for this
species to undergo subclinical (asymptomatic) so
there is a tendency of infection to go over a long
period of time which allow the stimulation of the
immune system.
Since it takes a long time for the development of
parasites in P. malariae and has lowest degree of
infection, immune system is given sufficient time to
be stimulated. The parasites will serve as the antigen
and upon stimulation of the immune system, there is
going to have antibody production leading to
production of AG-AB complex in the circulation.
This complex are bigger molecules and cannot be
filtered at the kidney so it will only adhere and
deposited on BM of glomerulus that will result to
acute glomerulonephritis (deposition of Ag-Ab
complex at the BM of the glomerulus of the kidney)
the patient had edema and hematuria (smokey red
color of urine)
Can also be secondary to sepsis and acute tubular
necrosis
5. GIT dysentery
Malaria infected individual can present with diarrhea
The segmental or focal ischemia to the walls of the
intestine will disrupt the normal peristalsis resulting
to hypermotility of the intestinal tract
6. Algid malaria
Occurs when there is a sudden drop in the blood
pressure of the infected person
There is possibility of having shock d/t the following
causes:
01132012
 DIC severe malaria can lead to hypoglycemic attacks

Sepsis the ischemia or anoxia to the liver is affecting hepatic

gluconeogenesis (production of glucose by way of the
Dehydration due to profuse or severe sweating liver)
blood volume CO shock
Treatment
7. Pulmonary edema
chloroquine , amodiaquine
Iatrogenic (d/t the doctor himself)
- oldest drug
Secondary to overzelousness of correcting fluid
- used for prophylaxis
8. Tropical splenomegaly syndrome (TSS)
- the parasite has to develop and undergo binary
Quite seen among children in Africa fission for the drug to take its effect

a condition wherein the patient had the treatment - not effective for sporozoites
already and yet splenomegaly is still persistent which
is capable of destroying the red cells even the normal quinine/ quinidine
ones. The patient end up being anemic also.
mefloquine
Splenectomy to prevent further destruction of RBC.
Only to find out that these patients are ending up primaquine
with bacterial infection particularly pneumonia.
Splenectomized patients are very prone to - the only drug that is effective in killing
pneumonia. gametocytes to prevent the local mosquito
from being infected and spread of malaria to the
Malarial pigment still present in the blood circulation community
is the one that consistently stimulate the spleen to
enlarge so they extend the treatment beyond the - Not important in killing the parasite inside the
usual time (14 days) thats the time that red cells
splenomegaly had been already cleared off after
some time - Effective in killing the parasite inside the liver
cell particularly the hypnozoites
9. Hyperparasitemia
- To prevent relapse and recrudescence
Due to severe infection
Artemisin
Can cause problems in the sense that all other
complications can set in all complications are - newest drug (from ginseng roots)
expected to occur
tetracycline
Connected to P. falciparum
- antibiotic
There are factors to consider
- kill malaria parasite to a very minimal degree
5% degree of infection (pernicious
- no sign and symptoms manifested can lead to
malaria severe)
subclinical manifestation
10% of the 5% has multiple infection
- theres a tendency of infection to go over a long
Presence of intermediate forms in the period of time
blood film from growing
***all the drugs listed have good killing ability except primaquine
trophozoites to mature schizonts
and tetracycline (no effect on erythrocytic form)
***young trophozites and gametocytes seen in
NONE of these drugs can kill and effective for sporozoites. Drug for
peripheral blood
sporozoite is an effective prophylaxis because it will not permit the
10. Hypoglycemia entry of organism into the liver cell

coma, seizure, delirium

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