YL6: 04.

15 Malaria
10/09/2019 Basic Pathologies 2
12:30-02:30 Julius Migriño Jr., MD
PARASITOLOGY

TABLE OF CONTENTS • Africa contains most of the cases of malaria

I. INTRODUCTION .................................................................................. 1
A. OVERVIEW ................................................................................ 1
B. GLOBAL DEMOGRAPHICS ....................................................... 1
C. FACTORS THAT INFLUENCE MALARIA EXISTENCE ............ 1
II. LIFE CYCLE ........................................................................................ 1
A. TERMINOLOGIES ...................................................................... 1
B. LIFE CYCLE ............................................................................... 2
C. TARGETING OF RED BLOOD CELLS ...................................... 3
D. SIGNS & SYMPTOMS RELATED TO EACH CYCLE ................ 3
III. CAUSATIVE AGENTS OF MALARIA ................................................. 3
A. PLASMODIUM FALCIPARUM ................................................... 4
B. PLASMODIUM VIVAX ................................................................ 6
C. PLASMODIUM OVALE .............................................................. 6
D. PLASMODIUM MALARIAE ........................................................ 7
E. PLASMODIUM KNOWLESI........................................................ 7
IV. SUMMARY OF PLASMODIA SPECIES DIFFERENCES .................. 7
A. DIFFERENT CHARACTERISTICS ............................................. 7
V. SYMPTOMS ........................................................................................ 8
A. STAGES OF FEBRILE PAROXYSM .......................................... 8
B. UNCOMPLICATED AND SEVERE MALARIA............................ 9
VI. DIAGNOSIS ....................................................................................... 9 Figure 1. Global Demographics of malaria. (Cibulskis, 2011)
A. METHODS .................................................................................. 9
QUICK REVIEW .................................................................................... 10 C. FACTORS THAT INFLUENCE MALARIA EXISTENCE
SUMMARY OF TERMS ................................................................ 10 • Where Malaria is found depends mainly on climatic factors, which
REVIEW QUESTIONS .................................................................. 12 include:
REFERENCES ...................................................................................... 12
® Temperature
REQUIRED ................................................................................... 12
APPENDIX ............................................................................................. 13 ® Altitude
® Humidity
® Rainfall
® Seasons
NOTE
• Doc said that more questions will come from this lecture as Temperature
compared to his other lectures (ex. Blood Flagellates) • The Anopheles mosquitos reside in warmer areas
® “Kasi importante talaga ang Malaria” • The global temperature is expected to rise because of climate
• Most questions will be on the pathophysiology, life cycle, and change
differentiation ® This can lead to an increase in the incidence of malaria
• For the anti-malaria drugs, he’ll only focus on the important stuff
including the mechanism Altitude
® This is a different trans by TG12 • The vectors that carry malaria do not reside in cold areas
• Bolded statements are the words he emphasized in his ® Mountains are cold so you do not expect the Anopheles
PowerPoint mosquitoes to reside there
• The mosquito that carries P. vivax is more tolerant to the cold and
can be seen in higher altitudes compared to those that carry P.
HELLO TO THE CRAMMERS falciparum
• The appendix is your best friend if you do not have enough time
to read everything II. LIFE CYCLE
® Just memorize the tables in the appendix and quick review A. TERMINOLOGIES
then you’ll get points for sure!

EXO-ERYTHROCYTIC VS ERYTHROCYTIC
I. INTRODUCTION • Exo-erythrocytic schizogony (EE)
A. OVERVIEW ® Found outside the erythrocyte
• The incidence of Malaria has been going down in the past decade ® Involved in liver invasion
® However, in the past 3 years, the number of cases has ® This is the upper right blue cycle in Figure 2
plateaued • Erythrocytic schizogony
• The goal is to decrease the number of cases by 40% by 2020 ® Found inside the erythrocyte
• The protozoan Plasmodium is the organism that causes malaria ® This is the lower right blue cycle in Figure 2
® P. falciparum
® P. vivax
® P. ovale Exo-Erythrocytic (EE) Schizogony
® P. malariae • Sporozoite
® P. knowlesi ® The things that the mosquito injects into the body
® Refer to number 1 on Figure 2
World Malaria Day 2018 • Schizonts – “the carrier ship”
• “Zero malaria starts with me” ® Once the liver cells are infected by the sporozoites, the
• April 25, 2019 schizonts are formed
• Merozoites – “the daughter aircrafts”
B. GLOBAL DEMOGRAPHICS ® The tiny things inside the schizonts
• Over 40% of the world’s population live in areas where malaria is § Refer to the red dots on numbers 3 and 4 in Figure 2
transmitted ® These are responsible for infecting the red blood cells after
® Generally, the countries with malaria are those near the coming out of the schizont
equator
® This is dictated by the vector, the mosquito, which lives in Erythrocytic Schizogony
tropical areas • Ring-stage

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 ® Important for the “food cup” which is used for digestion of the
hemoglobin for the parasite’s nutrition
• Trophozoites
® May differentiate into:
§ Schizonts – continue erythrocytic cycle inside human
§ Gametocyte – enter sexual cycle inside mosquito
• Schizonts
® Carrier of multiple merozoites via mitosis by binary fission
• Merozoites
® Will look for uninfected red blood cells which will then repeat
the erythrocytic cycle

NOTE
• Doc did not emphasize so much on “gametocytes” and
“sporogenic cycle” because he said “right now what happens
inside the mosquito is not important to us”

Gametocytes
• Microgametocytes
® Male gametocyte
• Macrogametocytes Figure 2. CDC Diagram of Malaria Parasite Life Cycle Involving Two
® Female gametocyte Hosts (CDC, 2018)
® Fertilization of both happens inside the mosquito

Sporogonic Cycle NOTE

(C) Sporogonic Cycle
• Zygote
• Ookinetes • Doc emphasized that this cycle is not included in the exam and
• Oocysts is not necessary to study
• Sporocytes • Mosquitos are not affected by the multiplication of parasite
inside them!
• Sporozoites
• Important to take note of is what comes in and what comes out
® Infective stage of Plasmodium
of the mosquito
® The one injected into the human host
® What comes in? Gametocytes
® What comes out? Sporozoites
B. LIFE CYCLE
Vector
Anopheles mosquito (A) Exo-Erythrocytic Cycle/Schizogony
• Very important in the cause and transmission of the Plasmodium 1. Mosquito takes a blood meal
parasite • Sporozoite (refer to #1 on Figure 2)
• Only 30-50 species of Anopheles sp. transmit malaria ® The infective stage of Plasmodium
® A. flavirostris (most common), A. maculatus, A. balabacensis, ® The sky-blue things that are injected by the female Anopheles
A. litoralis mosquito into the human host
• About a dozen or hundreds of sporozoites roam around the blood
NICE TO KNOW circulation until it reaches the liver cells
How to differentiate Dengue and Malaria Vectors
2. Sporozoites infect liver cells
• If the leg and body of the mosquito are striped, it can be a vector
for either • The liver cells (or hepatocytes) (refer to #2 on Figure 2)
• If the butt of mosquito is pointed upwards, it is Anopheles sp. ® It is the first stop in primary infection of the exo-erythrocytic
cycle
§ This is because everything passes through the liver
Incubation Periods • This is the initial staging ground of Plasmodium where they plan
• This refers to how long Plasmodium stays in the liver their invasion
® The period is quite long on the average of 1 ½ to 4 weeks
depending on the species 3. Infected liver cells mature into schizonts
• The reason why people do not manifest the symptoms of Malaria • Schizonts
immediately right after being bitten ® When liver cells become infected by the sporozoites, we call
• Plasmodium spp. incubation periods: them schizonts
® 9 to 14 days: P. falciparum – the shortest period ® Multiply via binary fission to produce and contain multiple
® 12 to 18 days: P. vivax and P. ovale merozoites (refer to #3 on Figure 2)
® 18 to 40 days: P. malariae – the longest period • Infection of liver cells is not that active because only a few
® 11 to 12 days: P. knowlesi hundred are affected
® When ready, they would then infect red blood cells

MEMORY TECHNIQUE 4. Rupture of schizont

• FASTiparum – fasted or shortest period • The mature schizont bursts and releases merozoites (refer to #4
• MAtagaLariae- longest period on Figure 2)
• Needs thousands to attack simultaneously
Overview of the Plasmodium CDC Cycle
• Reproductive stages: (B) Erythrocytic Cycle/ Schizogony
® Sexual stage (or fertilization) happens inside the mosquito • An asexual cycle that is synchronous, periodic, with certain
involving microgametes and macrogametes patterns, and species-determined
® Asexual stage happens inside humans
5. Merozoites infect RBCs
• Vector hosts:
® Definitive host – mosquito where fertilization happens • Merozoites
® Intermediate host – humans since no fertilization happens ® After exiting the ruptured liver cells, merozoites enter the
bloodstream
® They now infect red blood cell
® Inside red blood cell, they would form the young trophozoite
or the ring stage

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• Young trophozoites (or Ring stage)
® Comprised of a “diamond” and a “ring”
§ Usually, a merozoite produces one “diamond” per red
blood cell but can also be multiple
o Exception: P. falciparum can infect same red blood
cell with multiple merozoites resulting to multiple
diamonds in a single ring
§ However, each merozoite will only form one “ring”
® This structure (on Figure 3) is due to the formation of food
cup
§ The ring structures are responsible for ingesting the
hemoglobin of red blood cells
§ Read: “Why does Plasmodium target the red blood
cells?”
Figure 3. Ring-form trophozoites of P. falciparum in a thick blood
smear (MCDI, 2009a).
• Mature trophozoites (refer to the area on the right of the blue letter
“B” on Figure 2)
® These will mature into schizonts
• Schizonts
® These will divide asexually by binary fission to form multiple
merozoites
Figure 4. Schizonts of P. falciparum (MCDI, 2009b).
6. Mature schizonts rupture releasing merozoites
• When the schizonts becomes too full of merozoites, it will rupture
and release the multiple merozoites
• Each merozoite will then look for uninfected red blood cell
• Erythrocytic cycle repeats
8. Anopheles mosquito ingests gametocytes during a blood meal
4 Note: Not discussed by Doc Julius. Feel free to skip!
4 Gametocytes differentiate into either female (macrogametocytes)
or male (microgametocytes)
4 Ingested gametocytes unite to form an oocyst, which ruptures to
release sporozoites within the vector
4 Gametocytes are the ones that need to be ingested by Anopheles
mosquito for the cycle to close itself
SUMMARY OF PLASMODIUM LIFE CYCLE
1-4 (Exo-erythrocytic), 5-6 (Erythrocytic), 7-8 (Gametogenic)
Anopheles mosquito takes a blood meal
® Infective stage: sporozoites
Sporozoites infect liver cells
® Hypnozoites of P. vivax and P. ovale remain quiet for years
® Staging area for invasion
Infected liver cells mature into schizonts
® Via mitosis or binary fission
Rupture of schizont
® Release of merozoites
Merozoites infect red blood cells
® Merozoites become the ring stage of trophozoites
Mature schizonts rupture releasing merozoites
® Via mitosis or binary fission
® Erythrocytic cycle repeats
Some trophozoites differentiate into sexual erythrocytic stages
(gametocytes)
Gametocytes are ingested by Anopheles mosquito during blood
meal
C. TARGETING OF RED BLOOD CELLS
WHY DOES PLASMODIUM TARGET THE RED BLOOD CELLS?
• Plasmodium targets red blood cells because of the proteins
found in hemoglobin
® The protein component of hemoglobin is Plasmodium’s
main source of energy
§ Globin is the protein component of hemoglobin
• It is important to understand how plasmodium degrades
hemoglobin for energy to understand the mechanism of anti-
malarial drugs
® When Plasmodium degrades hemoglobin for its protein
component, it produces a by-product called heme
§ It is the non-protein component of hemoglobin
§ It is toxic for Plasmodium which is why it needs to be
detoxified by converting heme to hemozoin
§ Most anti-malarial drugs target the synthesis of
hemozoin from heme in order to target Plasmodium
D. SIGNS & SYMPTOMS RELATED TO EACH CYCLE

Table 1. Major Signs and Symptoms Associated with Each Cycle

Cycle Signs and Symptoms
• Jaundice
• Elevated liver enzymes
Exo-Erythrocytic Cycle
• Abdominal, RUQ pain
• Abdominal tenderness
• Major sign: Anemia
Erythrocytic Cycle ® The major pathophysiology:
red blood cell bursting out

Figure 5. Ruptured schizont of P. vivax in a thin blood smear, showing POP QUIZ!
free merozoites and pigment (MCDI, 2009c). • What do you call the things that infect red blood cells?
• What do you call the things the mosquito injects in the body?
Gametogonic Cycle
• Not actually a cycle because it does not close Answers:
• Important because this “cycle” produces gametes which are Merozoites, Sporozoites
needed for the sexual cycle stage

7. Some trophozoites differentiate into gametocytes III. CAUSATIVE AGENTS OF MALARIA

• Some trophozoites opt to become gametocytes instead to be able
to fulfill the sporogonic cycle (refer to #6 on Figure 2) NOTE
• It needs to be the gametocyte stage which will propagate inside the • We opted to change the flow of the lecture because we feel it
mosquito then transmitted to another human beings would be easier to understand in this format
• It comprises very small percentage as most trophozoites mature
into schizonts

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• Protozoan parasites of the genus Plasmodium
® P. falciparum
® P. vivax
® P. ovale – a close relative of P. vivax
® P. malariae
® P. knowlesi – relatively new species officially included (5 to 6
years ago) in the list of human Plasmodium species
Figure 6. P. falciparum female gametophyte (Bousema, 2011)
A. PLASMODIUM FALCIPARUM
• Very notorious compared to the other Plasmodium species
® Shorter incubation period
® Unpredictable fever pattern
® Pathophysiology is generally more serious and complicated
§ Due to its variant surface antigens
• Incubation period: 9 to 14 days
® Shortest among all the Plasmodium species
• Only gametocytes and young trophozoites (ring stage) of P.
falciparum are seen in peripheral blood smears
® Trophozoites and schizonts are still there, but they are stuck
to the endothelium of blood vessels
® This can then be used in the diagnosis of falciparum malaria
and non-falciparum malaria
® If gametocytes and young trophozoites are seen in the
peripheral blood smear of a patient suspected of having
malaria, then it is possible that he/she has P. falciparum
malaria
® If late trophozoites and schizonts are seen in the peripheral
blood smear of a patient, then it is possible that he/she has
non-falciparum malaria
Variant Surface Antigens
NEED TO KNOW
• Doc said it’s important to remember these surface antigens,
especially PfEMP-1, which is the most important among the
four. He did not discuss the others; he just listed them.
• Types:
® PfEMP-1
§ Plasmodium falciparum erythrocyte membrane protein-1
§ The only surface antigen that is present only in P.
falciparum
o The other three are present in all Plasmodium
species
§ It is also the only surface antigen that can stick to the
endothelium of blood vessels
§ Becomes manifested on the plasma membrane of
parasitized RBCs at the trophozoite or schizont stage
during the late phase of the erythrocytic cycle
® HRP-2: Histidine-rich protein 2
® A/B RIFIN
4 Repetitive Interspersed Family of Polypeptides
® STEVOR
• Infected/Parasitized RBCs express these surface antigens
because of the P. falciparum infecting them
• Why are variant surface antigens important?
® They contribute to the stickiness of RBCs parasitized with
P. falciparum
Pathogenesis
• Parasitized cells tend to become “sticky”
• P. falciparum produces a lot of surface antigens, particularly
PfEMP-1
® They are then expressed on the plasma membrane of the
infected RBCs
® Thus, “para silang mga adhesion proteins” (Migriño, 2019)
® These surface antigens make parasitized RBCs sticky
® This means that they stick to:
YL6: 04.15 Basic Pathologies 2: Malaria
§ Each other
§ Parasitized RBCs, and
§ Non-parasitized RBCs
Parasitized RBCs and Endothelium of Blood Vessels
NEED TO KNOW
• Since P. falciparum is the only one among the Plasmodium
species that produces PfEMP-1, it is the only Plasmodium
species that is capable of sticking to the endothelium and
escaping destruction by the spleen.
® Remember: P. falciparum = PfEMP-1
• Remember this because Doc kept repeating this!
• Parasitized RBCs also stick to the endothelium of blood vessels
(see Figure 7)
® The evolutionary advantage of being sticky is that:
§ P. falciparum is able to develop an immune evasion
protocol
§ Because of this, they do not get destroyed as much
because of their stickiness
§ This stickiness is, again, produced by the variant surface
antigens, particularly PfEMP-1
® Sticking to the endothelium of blood vessels means that they
stay inside a certain region of the body
§ They don’t get transferred to the spleen
§ The job of the spleen is to destroy infected/parasitized
RBCs
§ Since the spleen is the one trying to kill these infected
RBCs, splenomegaly is common due to malaria
infection, especially in the middle to late stage
§ But since the RBCs parasitized with P. falciparum are not
transferred to the spleen, they are safe from this
splenic destruction
Figure 7. Pathogenesis of P. falciparum (Migriño, 2019)
NOTE
• There is no need to memorize everything in the figure above.
• Doc said that what we should just remember is that all four
surface antigens stick to RBCs, but only PfEMP-1 (encircled
yellow in the figure above) can stick to the endothelium of
blood vessels.
• Some of the symptoms of severe P. falciparum malaria are caused
by blockage of the circulatory system
® This is caused by the stickiness of parasitized RBCs that
allow them to adhere to the endothelium of blood vessels
® These involve organs with narrow microvasculature such as:
§ Brain
§ Kidney
§ Lungs
§ Liver
• CSA receptor (encircled orange in figure 7 above)
® Receptor in the endothelium of the fetus
® Important in the congenital transmission of malaria,
especially P. falciparum malaria
® This receptor enables the P. falciparum-infected RBCs to bind
to the fetus
® This is why pregnant women are at high risk for complications
of malaria, especially for P. falciparum malaria
4 of 15
 CLINICAL CORRELATE: CEREBRAL MALARIA
• Since P. falciparum causes stickiness of parasitized RBCs,
these RBCs, as well as non-parasitized RBCs clump together
• They then form rosettes in certain parts of the endothelium
• If they clump together in the narrow microvasculature of the
brain, they then block the circulation in these areas
• Emboli are formed, thereby causing cerebral malaria
• This is why cerebral malaria is only found in P. falciparum
infections
® Because remember: P. falciparum is the only one that
produces PfEMP-1, which causes parasitized RBCs to
stick to the endothelium

Figure 8. Ring-form trophozoites of P. falciparum (MCDI, 2009a)

P. falciparum is really just the crappiest of them all. -Dr. Migriño
Schizont
Distinguishing Characteristics
• Medium size
• Compact
NOTE • Numerous chromatin masses
• For the following sections (until Plasmodium knowlesi), • Coarse pigments
everything with the previous trans bullet under the • It is rarely seen in peripheral blood
“Distinguishing Characteristics” section came from the 2022 4 Irregularly shaped
summary table that was sent in the batch chat (see the 4 8-24 merozoites
Appendix)
• Upperclassmen said that these were the ones that were asked
in their exam, but please take this with a grain of salt and still
study the rest because they were discussed by Doc J
• Doc also said that questions about stippling (i.e., Maurer’s
clefts, Schuffner’s dots, etc.) will surely be included in the
exam!
• There is a complete summary table (Appendix Table 1) for the
distinguishing characteristics of all the Plasmodium species that
were discussed in the appendix J
® Feel free to skip this section (until Plasmodium Knowlesi)
and study the figures in the appendix if you prefer learning
in table format
® We also included IV. Summary of Plasmodia Species
Differences if tables and mnemonics help you remember J
® If you’ll skip, just make sure to read the definitions before
moving on box and the relapse vs. recrudescence box!
Figure 9. Schizont of P. falciparum (Kho, 2003)
Red Blood Cells Gametocyte
• Size: not enlarged • Crescent-, banana- and sausage-shaped
• Shape: round, sometimes crenated 4 Defining diagnostic feature of P. falciparum; ultimately
• Color: distinguishes it from P. vivax and P. malariae
® Normal, but may become darker • Larger and slender
® May have a purple rim • Central chromatin
4 Predilection: All ages, no predilection

Stippling
• Maurer’s spots/clefts
® Appear as large red spots, loops, and clefts
4 These are protein accumulations in the erythrocyte cytosol,
seen in the ring stage
• Up to 20 or fewer

Pigment
• Black or dark brown
• In asexual forms: as one or two masses
• In gametocytes: as about 12 rods

Early Trophozoite (Ring) Figure 10. Gametocytes of P. falciparum (MCDI, 2009d)

• Smallest, delicate
• Sometimes two chromatin dots Periodicity
• Multiple rings commonly found
4 3-5 in a single RBC
DEFINITIONS BEFORE MOVING ON
• Quartan fever patterns – fever spikes every 72 hours or every 3
days
• Tertian fever patterns – fever spikes every 48 hours or every 2
days
• Quotidian fever patterns – every 24 hours
• Benign fever patterns – can be predicted when fever will spike
next
• Malignant fever patterns – cannot predict when fever will spike
next

4 P. falciparum is malignant tertian

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 POP QUIZ!
• Which surface antigen produced by P. falciparum can stick to
the endothelium of blood vessels?
• What is the stippling pattern seen in P. falciparum smears?

Answers:
PfEMP-1, Maurer’s spots/clefts

B. PLASMODIUM VIVAX
• All asexual stages can be seen in smears
® Thus, you should expect to see schizonts, trophozoites,
gametocytes
• Most important differentiating characteristic: its ability to remain
dormant in the hepatocytes as hypnozoites Figure 11. Ring-form trophozoites of P. vivax (CDC, n.d.)
® This causes malarial relapse
® Thus, it is important to kill the dormant hypnozoites in the liver Schizont
as well in order to prevent relapse • Large
• Incubation period: 12 to 18 days • Amoeboid
• Numerous chromatin masses
RELAPSE VS. RECRUDESCENCE • Fine pigments
• Malarial relapse – caused by P. vivax or P. ovale 4 12-24 merozoites (approximately, 16)
® You have malaria
® You get treated
® There are no more malaria parasites in your blood upon
testing
® After a long period of time, you get malaria again even
though you did not go to places where malaria is endemic
® This is because of the dormant hypnozoites in the liver
relapsing to give you another round of malaria
® It is a true relapse only when it is caused by P. vivax or P.
ovale
• Malarial recrudescence – caused by P. falciparum
® “Fake relapse” (Migriño, 2019)
® You have malaria
® You get treated
® You feel better already Figure 12. Schizont of P. vivax (MCDI, 2009)
® But suddenly, you have malaria again after a few weeks
® Unlike malarial relapse, this is due to P. falciparum Gametocyte
infection • Spherical, ovoid
• Compact
Distinguishing Characteristics
Red Blood Cells
• Size: enlarged
• Shape: round or oval, frequently bizarre
• Color: normal to pale
4 Predilection: reticulocytes

Stippling
• Schuffner’s dots
® Appear as small red dots
® Numerous
4 This is a peculiar stippling pattern observed from an enlarged
red cell as a trophozoite grows inside it

Pigment Figure 13. Gametocytes of P. vivax (MCDI, 2009)

• Haze of fine golden-brown granules scattered through the
cytoplasm Periodicity
4 Benign tertian: 1st and 3rd day
Early Trophozoite (Ring)
• Relatively large POP QUIZ!
• One chromatin dot, sometimes two • Malarial recrudescence is caused by P. ovale. True or False?
• Often two rings in one cell • What is the stippling pattern seen in P. vivax smears?
4 Big ring stage
4 Compact Answers:
False, it is caused by P. falciparum; Schuffner’s dots

C. PLASMODIUM OVALE
• P. vivax and P. ovale are similar to each other in almost all aspects
• All asexual stages can be seen in smears
• Most important differentiating characteristic: its ability to remain
dormant in the hepatocytes as hypnozoites
® This causes malarial relapse
• Incubation period: 12 to 18 days

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 Distinguishing Characteristics
Red Blood Cells
• Size: enlarged
• Shape: round or oval, often fimbriated
• Color: normal
4 Predilection: enlarged younger reticulocytes

Stippling
• James’ dots
® Numerous small red dots
4 Larger and darker dots than those found in P. vivax

Pigment
• Intermediate between P. vivax and P. malariae

Early Trophozoite (Ring)

Figure 16. Gametocytes of P. ovale (CDC, n.d.)
• Compact
• One chromatin dot
! One to two rings POP QUIZ!
! Two rings are rare • The incubation period of P. ovale is ______.
4 Big ring stage • The stippling pattern seen in P. ovale smears is Schuffner’s
4 Compact dots.

Answers:
12-18 days; False, it has James’ dots

D. PLASMODIUM MALARIAE
• Incubation period: 18 to 40 days
• All asexual stages can be seen in the smear

Distinguishing Characteristics
• Every 72 hours (quartan fever) – fever spikes
• Compact parasite
• Infects smaller, more mature RBCs
• Trophozoite ring has basket/band forms
• Schizonts are small and compact, contain 6-12 merozoites in a
rosette pattern (average of 9)
• Gametocytes are ovoid, like P. vivax, but smaller and less
numerous
Figure 14. Ring-form trophozoites of P. ovale (MCDI, 2009)
• Stippling: Ziemann’s dots
® Few tiny dots, characteristic of P. malariae
Schizont
• Medium size E. PLASMODIUM KNOWLESI
• Compact
• Causes Simian malaria
• Few chromatin masses
® Infects long-tailed Macaques (a genus of old-world monkeys)
• Coarse pigments
® Still considered as a zoonotic infection
4 6-14 merozoites (approximately, 9)
• Cases have been seen in Malaysia, Myanmar, Thailand, Vietnam,
Philippines, and Indonesia
• Current treatment protocols not yet established
• Incubation period: 11 to 12 days

Distinguishing Characteristics
Similarities with other Plasmodium spp.
• Morphologically similar to P. malariae
® Affects old, smaller red blood cells
® Stippling pattern: Sinton and Mulligan
® Can have band forms
• Clinically similar to P. falciparum
® Quotidian fever
§ Peak every 24 hours
® Causes anemia and thrombocytopenia
Figure 15. Schizont of P. ovale (MCDI, 2009) ® Also causes Acute Respiratory Distress Syndrome (ARDS)
® Does NOT have unarousable coma
Gametocyte
• Like P. vivax (ovoid) but smaller IV. SUMMARY OF PLASMODIA SPECIES DIFFERENCES
A. DIFFERENT CHARACTERISTICS
• Correlation between red blood cell size and age
® Big cell size corresponds to young age
§ E.g. immature red blood cells are usually bigger than
normal red blood cells
® Small cell size corresponds to older age
• Number of trophozoites per red blood cell
• Number of merozoites per schizont
• Number of chromatic dot/s per trophozoite
• Shape of gametocyte
® It is usually circular
• Stippling

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 ® These are the pigments in the infected red blood cell POP QUIZ!
® It can be due to either the by-products or proteins produced • Which Plasmodium has banana shaped gametocytes?
by the infective species
• Which Plasmodium has the smallest red blood cells?
Red Blood Cell Size and Age
Answers:
Table 2. Red blood cell size and age
P. falciparum; P. mallariae
Red Blood Cell Size
Species Size Mnemonics
V. SYMPTOMS
P. falciparum Normal-sized - • The incubation time for most plasmodium species is usually around
P. vivax Enlarged VIg (big) 2 weeks
P. ovale Enlarged ® Exception
-vale (big yung eyes & § Plasmodium malariae incubation time is more than 3
mouth niya) weeks
P. malariae Smaller MALiit si Kristin MALLARIae § Remember: MAtagaLariae
Red Blood Cell Age ® Incubation time: time between sporozoite injection and the
appearance of clinical symptoms
Species Age Mnemonics (Bernos, 2019) • No absolute clinical features of malaria except for febrile
P. falciparum All ages F*ck you all paroxysm
P. vivax Young Vavy/ Vata (bata, young) ® Febrile: feverish
® Paroxysm: a sequence of symptoms
P. ovale Young Offspring (young) • There are different symptoms for uncomplicated malaria and
P. malariae Old Matanda severe malaria
® Note: this will be discussed later in the trans
Number of Trophozoites
Table 3. Number of Trophozoites per Red Blood Cell A. STAGES OF FEBRILE PAROXYSM
Number of Memory technique • Fever patterns can help differentiate the Plasmodium species from
Species each other
Trophozoites
P. falciparum Multiple rings in a Always remember that • Overall paroxysm duration lasts 6-10 hours
single red blood cell falciparum is the most • Febrile paroxysm has three stages:
P. vivax Usually 1, rarely 2 in a malala! So, it has the ® Chills
single red blood cell most number. Everyone ® Fever
P. ovale Usually 1, rarely 2 in a else is more chill with ® Profuse Sweating
single red blood cell their 1-2 rings. ® Mnemonic: “CHoS” – Cold, Hot, Sweating
P. malariae Only 1 ring in a single
red blood cell

Number of Merozoites per Schizont

Table 4. Average Number of Merozoites per Schizont
Average Number of Mnemonics
Species
Merozoites
P. falciparum Around 24

P. vivax Around 16 -
P. ovale Around 9 Om9!!! (omg haha)
P. malariae Around 9 Om9!!! (omg haha) Figure 17. Febrile paroxysm of the Plasmodium species. (See bigger
P. knowlesi Still undecided I don’t Know picture in the appendix) (Migriño, 2019)

Shape of Gametocyte Chills (Cold Stage)

Table 5. Shape of Gametocyte • Usually happens midday
Species RBC Gametocyte Mnemonics • Occurs 15 minutes to 1 hour long
P. falciparum Banana/sausage/cigar- (Sorry for the R-18 • Coincides with the synchronized rupture of schizonts happen
shaped mnemonic) Falciparum ® There is a release of cell contents and by-products
f*cks most people over. § The release of these products triggers a huge cytokine
Bananas and sausages surge
do too. § The release floods the blood stream with the cytokines
P. vivax OVoid theM!!! (avoid from the inflammatory mediators
them) o Which then produces the initial chills
P. ovale OVoid theM!!! (avoid o Body will fight the release of these merozoites by
Ovoid -shaped releasing inflammatory cells (macrophages, white
them)
P. malariae OVoid theM!!! (avoid blood cells) which will then trigger the fever
them) response

Stippling Fever (Hot Stage)

Table 6. Stippling Pattern • Presents with high grade fever
Species Pattern • Usually lasts from 2-6 hours, depending on plasmodium species
P. falciparum Maurer’s dots/cleft ® P. malariae: benign quartan fever
P. vivax Schauffner’s dots § Fever spikes every 72 hours or every 3 days
P. ovale James’ dots ® P. vivax and P. ovale: benign tertian fever
P. malariae Ziemman’s dots § Fever spikes every 48 hours or every 2 days
P. knowlesi Sinton and Mulligan ® P. falciparum: on the average, every 24 to 48 hours
* Note: Doc said he might ask about Schauffner’s dots § Fever spikes are not consistent
§ Considered tertian because it’s every 48 hours however
it’s not routinely 48 hours (can be 24 hours or 36 hours)
§ Malignant tertian – temperature does not follow a routine
of 48 hours
• When the body has managed to clean up all the debris in the blood
stream and when the merozoites are able to go back in new red
blood cells, the body temperature center in the brain resets
® This would then trigger the profuse sweating stage

YL6: 04.15 Basic Pathologies 2: Malaria 8 of 15

 Profuse Sweating (Sweating Stage) ® Hyperparasitemia
• Lasts 2-4 hours after fever ® Hyperpyrexia
• Occurs right after fever spike ® Hyperbilirubinemia
• Diaphoresis or excessive sweating occurs
NICE TO KNOW
B. UNCOMPLICATED AND SEVERE MALARIA Subsets of Severe Malaria
• Malaria disease can be categorized as uncomplicated or severe
• Cerebral Malaria was mentioned by doc to be one of the subsets
(CDC, 2015)
of severe malaria. He just reiterated that we should be aware
• Febrile paroxysm the most common and important symptom for that severe malaria has a variety of subtypes
both categories

Uncomplicated Malaria Table 7. Summary of Major Differential Symptoms for Malaria

• To definitively differentiate for uncomplicated malaria, look for Uncomplicated Severe
these four symptoms: Chills* Hypoglycemia
® Chills, Fever, Sweating, Headaches Fever (on and off)* Acidemia
® NOTE: Headaches are not part of the markers for febrile Excessive Sweating* Acidosis
paroxysm (“CHoS”), but has been included in consistent Headaches Hyperparasitemia
symptoms for malaria *part of febrile paroxysm

Non-specific Symptoms VI. DIAGNOSIS

• All of these symptoms are seen in patients suffering from • Malaria should be included in diagnosing fever of unknown origin,
uncomplicated malaria, but are not consistently seen: regardless of travel history
® Headaches • There is a need to differentiate the 5 different species (discussed
® Jaundice in section III) based on:
§ This is because of increased liver enzymes ® Morphology
(hyperbilirubinemia) ® Pathogenesis
® Pallor ® Symptoms, Severity, Complications
§ This is because of thrombocytopenia or anemia ® Epidemiology
® Hepatomegaly/splenomegaly • Administrative Order 2009-0001: “Revised Policy and Guidelines
® Nausea, Vomiting on the Diagnosis and Treatment for Malaria” (Jan 13, 2009)
® Abdominal pain, diarrhea ® Note: Doc just mentioned this Administrative Order. He did not
® Dry cough talk about any of the details anymore
® Tachycardia
® Malaise/weakness A. METHODS
® Myalgia Microscopy
• Gold standard
Common Lab Findings ® “If you have the means to do this, do this!”
• CBC • Blood thick and thin smears
® Decreased hematocrit, hemoglobin, RBCs ® Every 6-12 hours for 48-72 hours
• General bloodwork ® GIEMSA/Wright-stained (take note of this!)
® Increase in liver enzymes and hyperbilirubinemia (associated • Thick smear:
with jaundice) ® Screening for the presence of infection
® Anemia and thrombocytopenia (associated with pallor) • Thin smear:
® Parasite density quantification
Malaria and Acidosis § Estimates the number of RBCs affected
• Almost all of the symptoms above are indicative of acidosis § If more than 5% of RBCs are infected, then it is most
® Plasmodium prefer an acidic environment likely already severe malaria
® Plasmodium utilize glucose from the human body which ® Species identification
leads to the host running out of glucose stores ® Visualize schizonts/gametes
® This triggers a compensatory gluconeogenesis response,
wherein lactate (an acid) is one of the major substrates
released
® Plasmodium utilizes this lactate by converting it to pyruvate
(and vice versa) via pLDH (plasmodium lactate
dehydrogenase)
® This conversion process is important for plasmodium’s life
cycle
® Thus, maintaining an acidic environment (acidosis) provides
plasmodium with a lot of lactate to utilize for maintenance of
their life cycle

Complicated/Severe Malaria
• When the disease is allowed to progress towards more life-
threatening conditions
Symptoms
• Hypoglycemia Figure 18. Sample Thick and Thin Blood Smear
• Acidemia/acidosis/hyperlactatemia
• Severe anemia Antigen/Enzyme Determination
• Renal failure • Dipstick (more common) or Cassette format
• Pulmonary edema/ARDS • Also called Rapid Diagnostic Test (RDT)
• Circulatory collapse • This is performed as a supplement to microscopy
• Abnormal bleeding/DIC ® You need to do this together with microscopy
• Repeated convulsions ® This test can work independently only in some special cases
• Macroscopic hemoglobinuria § There are some WHO approved rapid diagnostic test
• The following symptoms were recently added by WHO to help kits, which are accepted by some countries
differentiate uncomplicated vs severe anemia:
® Impaired consciousness
® Prostration/weakness

YL6: 04.15 Basic Pathologies 2: Malaria 9 of 15

Table 8. Common Enzymes/Proteins used for RDT Summary Table 1: Life cycle of Plasmodium
Enzyme/Protein Characteristics Life stage RBC Size
HRP-2 • Used in Parasight-F, ICT Malaria (specific Exo-erythrocytic cycle
RDTs) 1. Mosquito • Sporozoite: The infective stage of
• Falciparum-specific takes a blood Plasmodium
pLDH • Used in OptiMal (specific RDT) meal ® The one being injected by the
• Falciparum, vivax, and pan-specific female Anopheles mosquito into the
Aldolase • Pan-specific (common to all plasmodium human host
species) 2. Sporozoites • The liver cells are the first stop in
*Note that enzyme/protein specificity for species (i.e. vivax-specific) will infect liver primary infection of the exo-erythrocytic
not be asked according to doc. cells cycle
• This is the initial staging ground of
• PfEMP-1 Plasmodium where they plan their
® Not used in RDTs because this mutates very rapidly, so it is invasion
very hard to catch

3. Infected liver • Schizonts

cells mature ® Due to infection of sporozoites in
into schizonts liver cells then maturation
® Multiply via binary fission to
produce and contain multiple
merozoites
• Infection of liver cells is not that active
® When ready, they would then infect
red blood cells
Figure 19. Sample for RDT
4. Rupture of • The mature schizont ruptures and
schizont releases merozoites
POP QUIZ! • Needs thousands to attack
• Is acidosis more evident in complicated or uncomplicated simultaneously
Malaria?
• What is the gold standard method for diagnosis? Erythrocytic Cycle
5. Merozoites • Merozoites: From the liver cells, it enters
Answers: infect RBCs the bloodstream and infect red blood cell
Complicated; Microscopy • Young trophozoites: Comprised of a
“diamond” and a “ring”
® Formation of Food Cup
QUICK REVIEW
• Mature trophozoites: These will mature
SUMMARY OF TERMS into schizonts
• Terminology: • Schizonts: These will divide asexually
• Exo-Erythrocytic (EE) Schizogony by binary fission to form multiple
® Schizonts: Transformed from sporozoite upon liver cell merozoites
infection
® Merozoites: From the liver cell which infect the red blood 1. Mature • The rupture of schizonts releasing
cells schizonts multiple merozoites happens when the
• Erythrocytic Schizogony rupture red blood cells are too full and eventually
® Ring-stage: Important for the “food cup” which is used releasing loses energy
for digestion of the hemoglobin for its nutrition merozoites • Each merozoite will then look for
® Trophozoites: uninfected red blood cell
§ May differentiate into: • Erythrocytic cycle repeats
o Schizonts: Continue erythrocytic cycle inside
human Gametogenic cycle
o Gametocyte: Enter sexual cycle inside 7.Some • Some trophozoites become gametocytes
mosquito trophozoites to fulfill the sporogonic cycle
® Schizonts: Carrier of multiple merozoites via mitosis by differentiate • This stage needs gametocytes to
binary fission into sexual propagate inside the mosquito then
® Merozoites: Will look for uninfected red blood cells erythrocytic transmitted to another human beings
which will then repeat the erythrocytic cycle stages
• Gametocytes (Gametocytes)
® Microgametocytes: Male gametocyte
® Macrogametocytes: Female gametocyte 8. Gametocytes • Gametocytes differentiate into either
• Sporogonic Cycle are ingested macrogametocytes or microgametocytes
• Zygote by Anopheles • Ingested gametocytes unite to form an
• Ookinetes mosquito oocyst, which ruptures to release
• Oocysts during a blood sporozoites within the vector
• Sporocytes meal
• Sporozoites: Infective stage of Plasmodium
• Vector: Anopheles mosquito
• Incubation Periods: The amount of time Plasmodium stays • Causative agents of malaria
in the liver; period varies depending on species (avg. 1 ½ to ® Protozoan parasites of the genus Plasmodium
4 weeks) § P. falciparum
• Overview of the Plasmodium CDC Cycle § P. vivax
® Reproductive stages: § P. ovale
§ Sexual stage: Happens inside the mosquito § P. malariae
involving microgametes and macrogametes § P. knowlesi
§ Asexual stage: Happens inside humans • Plasmodium falciparum: Very notorious compared to the other
® Vector hosts: Plasmodium species, unpredictable fever pattern
§ Definitive host: Mosquito ® Variant Surface Antigens: Contributes to the stickiness of
§ Intermediate host: Humans RBCs parasitized with P. falciparum

YL6: 04.15 Basic Pathologies 2: Malaria 10 of 15

 § PfEMP-1: Plasmodium falciparum erythrocyte people over. Bananas
membrane protein-1 and sausages do too.
§ The only surface antigen that is present only in P. P. vivax OVoid theM!!! (avoid
falciparum. Found on the plasma membrane of them)
parasitized RBCs P. ovale OVoid theM!!! (avoid
§ HRP-2: Histidine-rich protein 2 Ovoid -shaped
them)
§ A/B RIFIN: Repetitive Interspersed Family of P. malariae OVoid theM!!! (avoid
Polypeptides them)
§ STEVOR
® Pathogenesis: Summary table 6. Stippling Pattern
§ Parasitized cells tend to become “sticky” Species Pattern
§ P. falciparum produces a lot of surface antigens, P. falciparum Maurer’s dots/cleft
particularly PfEMP-1 P. vivax Schauffner’s dots
o Which is expressed on the plasma membrane of P. ovale James’ dots
the infected RBCs
P. malariae Ziemman’s dots
§ Causes parasitized erythrocytes to become sticky to
P. knowlesi Sinton and Mulligan
each other, parasitized erythrocytes and non-parasitized
erythrocytes
® Parasitized cells and endothelium of blood vessels: • Symptoms:
§ P. falciparum can evade immune response ® Incubation time: time between sporozoite injection and the
§ Parasitized cells can stay in one part of the body, appearance of clinical symptoms
avoiding the spleen ® Varied incubation times (about 2 weeks, P. malariae ~3
§ Severe symptoms may involve the following systems weeks)
due to their microvasculature: ® Clinical features of malaria: febrile paroxysm
o Brain § Febrile: Feverish
o Kidney § Paroxysm: A sequence of symptoms
o Lungs ® Stages of febrile paroxysm
o Liver § Overall paroxysm duration lasts 6-10 hours
® CSA receptor: Important for congenital transfer of malaria § Febrile paroxysm has three stages:
• Defining/Distinguishing characteristics: For this section, please o Chills: Occurs 15 minutes to 1 hour long; coincides
refer to the appendix, Appendix Table 1 Summary Table for with the synchronized rupture of schizonts happen
Distinguishing Characteristics of Plasmodium species o Fever: Presents with high grade fever, lasts from 2-
6 hours, depending on plasmodium species (refer
Summary table 2. Red blood cell size and age to summary table x)
Red Blood Cell Size o Profuse Sweating: Lasts 2-4 hours after fever,
occurs right after fever spike, diaphoresis or
Species Size Mnemonics excessive sweating occurs
P. falciparum Normal-sized -
Summary table 2. Presentation of fever on Plasmodium species
P. vivax Enlarged VIg (big) Species Characteristics
P. ovale Enlarged -vale (big yung eyes & • Benign quartan fever
mouth niya) P. malariae • Fever spikes: every 72 hours or
P. malariae Smaller MALiit si Kristin MALLARIae every 3 days
• Benign tertian fever
Red Blood Cell Age
P. vivax and P. ovale • Fever spikes: every 48 hours or
Species Age Mnemonics (Bernos, 2019) every 2 days
P. falciparum All ages F*ck you all • Malignant tertian: Temperature
does not follow a routine of 48
P. vivax Young Vavy/ Vata (bata, young) hours
P. ovale Young Offspring (young) P. falciparum:
• Fever spikes are not consistent
P. malariae Old Matanda ® May occur every 24 to 48
hours
Summary table 3. Number of Trophozoites per Red Blood Cell
• Quartan fever patterns: Fever spikes every 72 hours or every 3
Number of Memory technique days
Species
Trophozoites
• Tertian fever patterns: Fever spikes every 48 hours or every 2
P. falciparum Multiple rings in a Always remember that days
single red blood cell falciparum is the most • Quotidian fever patterns: Every 24 hours
P. vivax Usually 1, rarely 2 in a malala! So, it has the
• Benign fever patterns: Can be predicted when fever will spike
single red blood cell most number. Everyone next
P. ovale Usually 1, rarely 2 in a else is more chill with
• Malignant fever patterns: Cannot predict when fever will spike
single red blood cell their 1-2 rings. next
P. malariae Only 1 ring in a single
• Uncomplicated and severe malaria: Malaria disease can be
red blood cell
categorized as uncomplicated or severe
® Febrile paroxysm is a common and the most important
Summary table 4. Average Number of Merozoites per Schizont
symptom for both categories
Average Number of Mnemonics
Species • Uncomplicated Malaria: Will have these four symptoms:
Merozoites
® Chills, Fever, Sweating, Headaches
P. falciparum Around 24
® Non-specific Symptoms:
P. vivax Around 16 - § Jaundice
§ Pallor
P. ovale Around 9 Om9!!! (omg haha)
§ Hepatomegaly/splenomegaly
P. malariae Around 9 Om9!!! (omg haha)
§ Nausea, Vomiting
P. knowlesi Still undecided I don’t Know § Abdominal pain, diarrhea
§ Dry cough
Summary table 5. Shape of Gametocyte § Tachycardia*
Species RBC Gametocyte Mnemonics § Malaise/weakness
P. falciparum Banana/sausage/cigar- (Sorry for the R-18 § Myalgia
shaped mnemonic) Falciparum ® Common Lab Findings
is the one the f*cks most § CBC: Decreased hematocrit, hemoglobin, RBCs

YL6: 04.15 Basic Pathologies 2: Malaria 11 of 15

 § General bloodwork: Increase in liver enzymes and 2. Plasmodium interacts with ____ in the food cup which enables the
hyperbilirubinemia, anemia and thrombocytopenia parasite to digest hemoglobin without being toxic to the parasites.
® Malaria and Acidosis: Plasmodium prefer an acidic The byproduct of this process is called______
environment a) Iron, Ferrous sulfate
§ Plasmodium utilize glucose from the human body b) Oxygen, water
o Results to host running out of glucose stores c) Water, carbon dioxide
§ Compensatory gluconeogenesis occurs where lactate d) Heme; hemozoin
is released 3. This triggers a massive release of inflammatory response, causing
§ Plasmodium utilizes this lactate by converting it to the chills and eventually the fever response.
pyruvate (and vice versa) via pLDH (plasmodium lactate a) Infection of hepatocytes
dehydrogenase) b) Maturation of trophozoites into gametocytes
• Complicated/Severe Malaria: When the disease is allowed to c) Rupture of schizonts
progress towards more life-threatening conditions d) NOTA
® Symptoms: 4. Bob Uy comes in the ER complaining of unexplained fever. You
§ Hypoglycemia suspect he has malaria. To confirm your diagnosis, you requested
§ Acidemia/Acidosis/Hyperlactatemia for his blood tests. What would you expect to see in his blood test?
§ Severe Anemia a) Hyperbilirubinemia, Anemia, Thrombocytopenia, Acidosis
§ Renal Failure b) Increased hemagglutination time
§ Pumonary Edema/ARDS c) Decreased insulin levels
§ Circulatory collapse d) Increased hematocrit, leukocytosis, alkalosis
§ Abnormal bleeding/DIC 5. Following up on Bob Uy’s case, histological findings include the
§ Repeated convulsions following descriptions:
§ Macroscopic hemoglobinuria RBC: Enlarged
§ The following symptoms were recently added by WHO Shape: Round/oval
to help differentiate uncomplicated vs severe anemia: Stippling: Numerous small red dots; Schuffner’s Dots
o Impaired consciousness Presence of a large ring
o Prostration/weakness What is the most likely plasmodium species that caused Bob’s
o Hyperparasitemia illness?
§ Hyperpyrexia a) P. falciparum
§ Hyperbilirubinemia b) P. malariae
c) P.vivax/ovale
• Diagnosis: Should be included in diagnosing fever of unknown d) NOTA
origin, regardless of travel history 6. This surface antigen is only seen in P. falciparum which causes the
• Differentiation of the 5 different species (discussed in section III) infected erythrocytes to become sticky?
based on: a) HRP-2
® Morphology b) A/B-RIFIN
® Pathogenesis c) PfEMP-1
d) NOTA
® Symptoms, Severity, Complications
7. Relapse of malaria can occur in malaria by P. vivax and P. ovale
® Epidemiology
due to persistence of a dormant stage called
• Gold standard: Blood smear a) Hypnozoites
® Blood thick and thin smears; done every 6-12 hours for 48-72 b) Merozoites
hours 8. True or false: one of the common enzymes/proteins used for rapid
® GIEMSA/Wright-stained blood to see plasmodium diagnostic tests is the HRP-2 which is Vivax-specific
® Thick smear: Screening for the presence of infection a) True
® Thin smear: Parasite density quantification and species b) False
identification 9. Microscopy is the gold standard for diagnosing malaria. The _____
• Antigen/Enzyme Determination/Rapid Diagnostic Tests (RDT): smear is used for parasite density quantification whereas the
Adjunct to microscopy, either in dipstick or cassette format _____ smear is used for confirming presence of infection
a) Thick, Thin
Summary Table 3. RDT Enzymes/proteins and their characteristics b) Thin, Thick
Enzyme/Protein Characteristics c) Big, Small
HRP-2 • Used in Parasight-F, ICT Malaria (specific d) Small, Big
RDTs) 10. At the erythrocytic stage of the life cycle of plasmodium, young
• Falciparum-specific trophozoites mature to and may become either mature trophozoites
pLDH • Used in OptiMal (specific RDT) or become ______ and enter the gametogenic cycle.
• Falciparum, vivax, and pan-specific a) Schizonts
Aldolase • Pan-specific (common to all plasmodium b) Merozoites
species) c) Hypnozoites
d) Sporozoites
e) Gametocytes
• Differentiation of Plasmodia species:
® Characteristics: Answers (if self-explanatory)
§ Correlation between red blood cell size and age
1. B
o Big cell size corresponds to young age of the cell,
2. D
small means older cells 3. C
§ Number of trophozoites per red blood cell
4. A
§ Number of merozoites per schizont
5. C
§ Number of chromatic dot/s per trophozoite 6. C
§ Shape of gametocyte
7. A
® Stippling: Pigments in the infected red blood cell which are 8. B
either the by-products or proteins produced by the infective 9. B
species 10. E

REVIEW QUESTIONS REFERENCES

1. One of the most significant life cycle stages, known as the infective
REQUIRED
stage of the plasmodium in its vector. It is the stage where the
(1) Cdc.Gov, 2019,
plasmodium gets injected from the vector to the host.
https://www.cdc.gov/dpdx/resources/pdf/benchaids/malaria/malari
a) Merozoites
a_comparison_p1-2.pdf. Accessed 9 Oct 2019.
b) Sporozoites
(2) Cdc.Gov, 2019,
c) Schizonts
https://www.cdc.gov/dpdx/resources/pdf/benchAids/malaria/Pviva
d) Trophozoites
x_benchaidV2.pdf.

YL6: 04.15 Basic Pathologies 2: Malaria 12 of 15

(3) Cdc.Gov, 2019, (10) "Malaria - Plasmodium Vivax: Schizonts". Mcdinternational.Org,
https://www.cdc.gov/dpdx/resources/pdf/benchAids/malaria/Poval 2019,
e_benchaidV2.pdf. https://www.mcdinternational.org/trainings/malaria/english/DPDx5
(4) "Atlas". Atlas.Or.Kr, 2019, /HTML/Frames/M-R/Malaria/vivax/body_malariadfvivschiz.
http://atlas.or.kr/atlas/alphabet_view.php?my_codeName=Plasmo Accessed 9 Oct 2019.
dium%20falciparum. (11) "Malaria - Plasmodium Vivax: Schizonts". Mcdinternational.Org,
(5) "CDC - Malaria - About Malaria - Biology". Cdc.Gov, 2019, 2019,
https://www.cdc.gov/malaria/about/biology/. Accessed 9 Oct https://www.mcdinternational.org/trainings/malaria/english/DPDx5
2019. /HTML/Frames/M-R/Malaria/vivax/body_malariadfvivschiz.
(6) "Malaria - Plasmodium Falciparum: Gametocytes". (12) Bousema, T., and C. Drakeley. "Epidemiology And Infectivity Of
Mcdinternational.Org, 2019, Plasmodium Falciparum And Plasmodium Vivax Gametocytes In
https://www.mcdinternational.org/trainings/malaria/english/DPDx5 Relation To Malaria Control And Elimination". Clinical
/HTML/Frames/M-R/Malaria/falciparum/body_malariadffalcgame. Microbiology Reviews, vol 24, no. 2, 2011, pp. 377-410. American
(7) "Malaria - Plasmodium Falciparum: Ring Stage Parasites". Society For Microbiology, doi:10.1128/cmr.00051-10. Accessed 9
Mcdinternational.Org, 2019, Oct 2019.
https://www.mcdinternational.org/trainings/malaria/english/DPDx5 (13) ASMPH Batch 2022. 2018, Malaria
/HTML/Frames/M-R/Malaria/falciparum/body_malariadffalcring.
Accessed 9 Oct 2019.
IMPORTANT LINKS
(8) "Malaria - Plasmodium Ovale: Trophozoites".
Mcdinternational.Org, 2019,
Trans feedback: https://tinyurl.com/AcadsTransFeedback
https://www.mcdinternational.org/trainings/malaria/english/DPDx5
Errata submission: https://tinyurl.com/ContentErrataSubmission
/HTML/Frames/M-R/Malaria/ovale/body_malariadfovatroph.
Errata tracker: https://tinyurl.com/ErrataTracker
(9) "Malaria - Plasmodium Vivax: Gametocytes".
Mcdinternational.Org, 2019,
https://www.mcdinternational.org/trainings/malaria/english/DPDx5
/HTML/Frames/M-R/Malaria/vivax/body_malariadfvivgame.

APPENDIX

Appendix Figure 1. Life cycle of Plasmodium species. Boxed figures are the ones emphasized during the lecture. Red Box: Important life cycle in
human disease. Green Box: Exo-erythrocytic cycle. Blue Box: Erythrocytic Cycle. Yellow Box: Gametocytes (Product of Gametogenic cycle/stage)

YL6: 04.15 Basic Pathologies 2: Malaria 13 of 15

Appendix Figure 2. Febrile paroxysm of the Plasmodium species. (Migriño, 2019)

Appendix Figure 3. Pathogenesis of Malaria. Boxed figures were emphasized in the lecture: Fever, Anemia, Acidosis

YL6: 04.15 Basic Pathologies 2: Malaria 14 of 15

Appendix Table 1. Summary Table for Distinguishing Characteristics of Plasmodium species (Migriño, 2019)

Appendix Table 2. Notes from 2022 (Recio, 2018)

Corrections on the table above:

*malarial relapse and hypnozoites are also seen in /P. ovale/ infections
**correction: /P. malariae/ schizont size is small not large

YL6: 04.15 Basic Pathologies 2: Malaria 15 of 15