PARASITOLOGY LECTURE

LE
01 - Malaria
Disraeli V. Europa, M.D. 03
TABLE OF CONTENTS I. INTRODUCTION
I. INTRODUCTION VI. STAGES OF MALARIAL ● Malaria is endemic in most tropics
A. Epidemiology PAROXYSMS → Accounts for 7.8% of the global disease burden
B. Anopheles minimus A. Recrudescence vs Relapse ● Emergence of Plasmodium falciparum resistance in Africa and
flavirostris VII. COMPLICATIONS
📋
Anopheles resistance to pyrethroid insecticides
C. Transmission A. P. knowlesi
Developing partial resistance to artemisinin, which is
D. Life Cycle B. P. malariae
1. Exoerythrocytic Stage C. P. falciparum supposed to be the most effective, is of great concern in

2. Erythrocytic Stage
3. Sporogonic Life Cycle
II. PLASMODIUM SPP.
A. Morphology
B. Ring-Form
C. Mature Trophozoite
D. Schizont
E. Gametocyte
III. MALARIAL PARASITE
A. Plasmodium vivax
B. Plasmodium ovale
C. Plasmodium malariae
D. Plasmodium falciparum
E. Plasmodium knowlesi
IV. PATHOGENICITY AND
VIRULENCE
A. Virulence
B. Pathogenicity
V. CLINICAL MANIFESTATIONS
A. Prepatent Period
B. Incubation Period
C. Prodromal Symptoms
1. Fever (blackwater)
2. Cerebral Malaria
3. Acute Renal Failure
4. Respiratory Findings
5. Anemia
6. Dysenteric Malaria
7. Algid Malaria
8. Poor Prognosis
D. Severe Malaria in Children
E. Other Complications
VIII. DIAGNOSIS OF MALARIA
A. Laboratory Tests
IX. TREATMENT OF MALARIA
A. Medications
1. Blood Schizonticides
2. Tissue Schizonticides
3. Gametocyticides
B. Uncomplicated P.
falciparum
C. Uncomplicated P. vivax or
P. ovale
D. Chemoprophylaxis
E. Malaria Prevention Tools
X. SAMPLE QUESTIONS
XI. REFERENCES
XII. APPENDIX
📋
Africa [2025]
So far, there has been no approved vaccine for malaria in any
country [2025]
A. EPIDEMIOLOGY
● Forty-nine out of 81 provinces are endemic for this disease
→ 73% in Luzon
→ 23% in Mindanao
→ 4% in Visayas
● As of 2013, Cagayan, Isabela, Palawan, Sulu and Tawi-Tawi have
the highest reported cases of malaria among provinces
→ In the same year, Rizal & Balabac (Palawan), Sitangkai,
South Ubian and Sapa-Sapa (Tawi-Tawi) have the highest
reported cases of malaria among municipalities
● Among blood smears examined from 2010 to 2013:
→ 68 - 79% had P. falciparum
→ 20 - 30% had P. vivax
→ 1 - 3% had mixed malarial infection
→ 1% had P. malariae
● Young children and pregnant women are mostly affected by
malaria
→ Those at risk include farmers, indigenous cultural groups,
miners, forest product gatherers and soldiers
● Transmission: Female Anopheles spp. mosquito bite

📖
LEGEND → Mainly between dusk and dawn

⭐ 💬 📖 📋
IMPORTANT LECTURE BOOK PREVIOUS TRANS Can also be transmitted through blood transfusion from infected
donors, use of contaminated needles and syringes and vertical
ABBREVIATIONS transmission before or during birth [Belizario, 2013]
ACTs Artemisinin-based combination therapies ● Falciparum and Ovale are primarily diseases of the Tropics
CXR Chest X-Ray ● Vivax malaria is the most common type in all endemic areas
DEET N,N-diethyl-m-toluamide ● The most common combination of mixed infection is P. vivax and
GP1 Glycoprotein 1 P. falciparum
HRP Histidine-rich Proteins
HRP II Histidine-rich Protein II
IFAT Indirect fluorescent antibody test
IHA Indirect hemagglutination
MDR Multidrug resistance
PfEMP1 P. falciparum erythrocyte membrane protein 1
pLDH Plasmodium lactate dehydrogenase
PMA Pan Malarial Antigen
TNF Tumor Necrosis Factor

LEARNING OBJECTIVES
● Differentiate the general characteristics of Plasmodium species
● Describe morphology of each individual Plasmodium species
● Analyze the Life cycle of Malaria
● Distinguish important epidemiological data and updates of
Malarial infection Figure 1. Population and epidemiological profile of Malaria [Lecturer’s PPT]
● Correlate clinical syndromes and complications of Malarial
infection to pathobiology of the parasite
● Recommend treatment and prevention plans

Malaria | Laguimun, Lam, Lama, Lao, A., Lao, M. AVPAA | Lecciones

PARA LEC | LE3 - 01 PAGE 1 of 22
VPAA | Maranan, Margallo TE | Ignacio
 Figure 4. Anopheles minimus flavirostris [Lecture PPT]
[Lecture PPT]
Figure 2. Graphical distribution of Malaria
C. TRANSMISSION
● Aside from mosquito bites, it can also be transmitted by
transfusion or use of shared syringes
● There are cases of vertical transmission
D. LIFE CYCLE

Figure 3. Malaria cases and deaths in the Philippines [Lecturer’s PPT]

B. ANOPHELES MINIMUS FLAVIROSTRIS
● Principal vector in the Philippines
● Night biter
● Usually reside in slow flowing streams, irrigation ditches,
ricefields, pools, and well
● Flight range: 1-2 kms
● Many are mildly exophagic, zoophilic and endophilic
→ Mosquito that tends to inhabit or rest indoors
● Temperature 16-34°C and >60% humidity favors breeding of
mosquitoes Figure 5. Life cycle of Plasmodium species [Lecturer’s PPT]
● Other Anopheles vectors: ● Asexual cycle: occurs in humans (vertebrate and intermediate
→ Anopheles litoralis host)
◼ Coastal areas of Mindanao and Sulu ● Sexual cycle: occurs in Anopheles mosquito (invertebrate and
◼ Saltwater breeder definitive host)
→ Anopheles maculatus
◼ Coexists with A. flavirostris in the portions of streams EXOERYTHROCYTIC STAGE
exposed to sunlight ● Occurs in the liver
◼ Higher altitudes 1. After a blood meal, sporozoites go to the liver
→ Anopheles mangyanus 2. These sporozoites are taken up by hepatocytes within 30
◼ Same breeding habitats and seasonal prevalence as A. minutes
flavirostris 3. In the liver, the parasite multiples, matures into schizonts
◼ Prefers habitants located in forest fringe (schizogony) and liver cells rupture producing merozoites
which is the infective stage for the RBC
● Schizonts are formed inside the hepatocytes
● Only P. vivax and P. ovale produce hypnozoites
→ Hypnozoites are latent form or dormant hepatic
schizonts
→ Remains dormant for years in the liver and later can
release merozoites causing relapses of the illness
4. Asexual cycle consisting of schizogony begins.
ERYTHROCYTIC STAGE
1. During this cycle, the RBCs are invaded by merozoites
2. Merozoites then transform into early ring trophozoites and then
become mature trophozoites
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3. From mature trophozoites, they develop into schizonts which
eventually rupture and release merozoites
4. After multiple merozoites have been produced, the circulating
erythrocytes may start to develop male (micro) and female
(macro) gametocytes which the feeding female mosquito may
take up
⭐Table 1. Plasmodium disease and periodicity
Species Disease Periodicity
P. vivax Benign tertian 48 hours
P. falciparum Malignant tertian 48 hours
P. ovale Ovale tertian 48 hours
P. malariae Quartian 72 hours
P. knowlesi Quotidian 24 hours

● Periodic release of merozoites causes typical recurrent symptoms

of chills, fever and sweating seen in malaria patients Figure 7. Life Cycle of Malarial Parasite in Mosquitoes [Lecturer’s PPT]
→ Merozoites invade and disrupts RBCs causing hemolysis II. PLASMODIUM SPP.
● P. falciparum is the deadliest A. MORPHOLOGY
● P. malariae is known for its chronicity
● P. ovale is NOT found in the Philippines
● P. knowlesi is relatively new with not much information about it yet

Figure 8. Morphological features [Lecturer’s PPT]

● In the Erythrocytic cycle, merozoites are released from the liver
cells and go into the circulation to infect RBC.
→ It will differentiate into ring-shaped trophozoites and grow into
amoeboid-form trophozoites which will differentiate into
schizonts that are filled with merozoites. After release, they
will infect other erythrocytes
● Merozoites recognize a specific receptor site on the RBC and
expose several organelles for attachment
→ RBC will become deformed and merozoites enter through an
Figure 6. Life Cycle of Malarial Parasite [Lecturer’s PPT] invagination of the RBC membrane.
SPOROGONIC CYCLE ● P. vivax has a receptor site that is associated with the Duffy
● Occurs in the Female Anopheles mosquito Blood group antigen
→ In humans, some merozoites will differentiate into sexual → >90% of Black Africans are Duffy Negative and are resistant
erythrocytic stages known as gametocytes to Vivax malaria
→ Male (microgametocytes) and female (macrogametocytes) ● Sickle cell trait confers resistance to P. falciparum
are ingested by an Anopheles mosquito during a blood meal ● G6PD deficiency also limits parasitemia
→ Microgametocytes exflagellates
◼ Removes its tail and produce 8 sperm-like microgametes
that will fertilize the female macrogametocyte to form a
zygote
→ The zygotes will become motile and elongate (ookinetes)
→ Ookinetes invade the midgut wall of the mosquito where they
develop oocysts
→ The oocytes will grow, rupture and release sporozoites,
which makes their way to the mosquito’s salivary glands
→ Sporozoites enter the salivary glands (infective stage to
humans)

Figure 9. Life Cycle of Plasmodium spp. [Lecturer’s PPT]

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 B. RING-FORM/EARLY TROPHOZOITE ⭐ Sexual form ingested by the mosquito (infective stage for
mosquito)
→ Macrogametocyte (female) - nucleus is dense and compact
→ Microgametocyte (male) - nucleus is a pale, loose network
● Gametocyte of P. vivax, P. ovale, P. malariae, and P. knowlesi are
very similar in shape (round or oval) and size
→ Except P. malariae which is smaller in size and darker

⭐Figure 10. (L) P. vivax: signet ring trophozoite. (M) P. falciparum: ● P. falciparum is banana-shaped or spindle-shaped
III. MALARIAL PARASITE
headphone type with double chromatin dot. (R) P. malariae: bird’s

⭐
A. PLASMODIUM VIVAX
⭐
eye ring form [Lecturer’s PPT]

⭐
Earliest stage after the invasion of the RBC. Most common malaria in the Philippines
● The ring is a dot-like nucleus of red chromatin Benign Tertian Malaria
● P. falciparum and P. knowlesi: headphone type with a double → Tertian = 48 hours + 1 day without fever
chromatin dot → Erythrocytic cycle: 48 hours

⭐
● P. vivax: Signet-ring form ◼ There is hemolysis of infected RBC every 48 hours
● P. malariae: Bird’s eye ring form Has a persistent/dormant stage (Hypnozoite) in the liver which
is the cause of relapse
C. MATURE TROPHOZOITE ● The predominant malarial species in most parts of the world
● Infected RBC is enlarged since Vivax has an affinity for young

📋
RBCs or Reticulocytes
Mnemonics: Vivax = Vata/Vivi = Young RBCs [2025]
● A single infectious bite can trigger 6 or more relapses a year,
leaving sufferers more vulnerable to other diseases
→ Other infectious diseases, including Falciparum malaria,
appear to trigger relapses
Figure 11. (L) P. falciparum: Maurer’s dot (R) P. vivax and P. ovale:
Schuffner’s dot [Lecturer’s PPT]
⭐Table 2. Morphology of P. vivax
● Hemozoin: darkly staining pigment produced by metabolized RING FORM TROPHOZOITE
hemoglobin
→ Parasite nutrition is hemoglobin and the metabolite is
hemozoin or hematin.
● Maurer’s clefts: seen in P. falciparum infections containing
older-ring form trophozoites and asexual stage
● ​Schüffner’s dots: seen in P. vivax and P. ovale
D. SCHIZONT
Figure 14. P. vivax Ring-form Trophozoite [Lecturer’s PPT]

Rings ⭐ Signet or ring-shaped

● Rings may be difficult to distinguish from those
of P. ovale
Size of infected ● Infected RBCs are often larger than uninfected
RBC RBCs
Cytoplasm ● Has a thick cytoplasm with a single, large

⭐
Figure 12. Schizont [Lecturer’s PPT] chromatin dot
● Final pathway in the maturation of malarial parasites. The cytoplasm becomes amoeboid and
● Multiple masses of nuclear chromatin are seen when parasites Schüffner’s dots may appear as the
divide. trophozoites mature
● Mature schizonts contain merozoites. Other features ● Multiply-infected RBCs may be seen.
● Falciparum schizonts are rarely seen in peripheral blood, except → Similar with P. ovale, P. falciparum, P.
in severe cases. knowlesi
→ Falciparum schizonts stay in capillaries of organs and
muscles LATE TROPHOZOITES
→ When infection is severe, it can spill into the general
circulation which indicates a bad prognosis.
E. GAMETOCYTE

Figure 15. P. vivax Late Trophozoites [Lecturer’s PPT]

Size of infected ● Infected RBCs are usually larger than
RBC uninfected RBCs

Figure 13. (L) P. falciparum: banana-shaped. (R) P. vivax, P. ovale,

P. malariae (smaller and darker), P. knowlesi. [Lecturer’s PPT]
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Cytoplasm ● Developing trophozoites become amoeboid, ⭐Table 3. Morphology of P. vivax
with pseudopodial processes and large RING FORM TROPHOZOITE
vacuoles.
→ Schüffner’s dots are visible with proper
staining
→ Small-yellowish brown pigment granules in
the cytoplasm, increasing with the age of
parasite
● Band-form appearance of the trophozoite may
occur Figure 18. P. ovale Ring-form Trophozoite [Lecturer’s PPT]
→ May be mistaken for band-form trophozoite
Rings ● Contains a single chromatin dot. May be difficult
of P. malariae and P. knowlesi

⭐
to differentiate from P. vivax
SCHIZONTS As the trophozoites mature, they may exhibit
fimbriation and Schüffner’s dots
→ Schüffner's dots regularly present in almost
100% of infected cells
Other ● Multiply-infected RBCs may be seen
features ● Ring forms are not headphone type (unlike those
of P. falciparum)
Figure 16. P. vivax Schizonts [Lecturer’s PPT] ● Several ring forms may be seen in within single

📋
RBC
Size of infected ● Infected RBCs are usually larger than
RBC Infected RBC shows granules like Schüffner’s
uninfected RBCs and may be amoeboid.
dots and take a violet tinge [2025]
Other feature/s ● Mature schizonts contain 12-24 merozoites,
MATURE TROPHOZOITES
each of which contains a dot of chromatin
and a mass of cytoplasm
● Pigment is usually organized in one or two
clumps
● Parasite almost fills enlarged cells
GAMETOCYTES

Figure 19. P. ovale Mature Trophozoites [Lecturer’s PPT]

Size of ● Infected RBCs are often slightly enlarged
infected RBC
Cytoplasm ● Exhibit fimbriation and Schüffner’s dots
SCHIZONTS

Figure 17. P. vivax Gametocytes [Lecturer’s PPT]

Size of infected ● Infected RBCs are often larger than uninfected
RBC RBCs
Other feature/s ● Macrogametocytes are round to oval
● Cytoplasm is usually a darker blue and Figure 20. P. ovale Schizonts [Lecture PPT]

●
contains fine brown pigment throughout
Schüffner’s dots may be seen with proper
Feature/s ⭐ Schizonts of P. ovale can be similar to P. vivax,
although tend to contain fewer merozoites (4-16,
staining
💬
on average 8)
● Microgametocytes are usually the size of
Infected RBCs are normal to slightly enlarge,
uninfected RBC.
⭐
round to oval shape
→ Paler blue, pink, or gray cytoplasm
Elongation to an oval shape and fimbriation are
common
⭐ Ovale Malaria
B. PLASMODIUM OVALE
→ Schüffner’s dots can be observed with proper
⭐ Benign Tertian Malaria staining
→ Erythrocytic cycle: 48 hours GAMETOCYTES
● Has a persistent/dormant stage (Hypnozoite) in the liver which
is the cause of relapse
● Infected RBC is slightly enlarged compared with the normal
RBC
● Found in Tropical Africa, West Africa, South America and Asia

Figure 21. P. ovale Gametocytes [Lecturer’s PPT]

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Size of ● Difficult to distinguish from P. vivax SCHIZONTS
infected RBC ● Slight enlargement of the infected RBC
→ The mature macrogametocyte fills the host
RBC
→ The microgametocyte becomes smaller
Other ● Schüffner’s dots may be seen with proper
feature/s staining and fimbriation may occur
→ Important in Africa to identify P. ovale, because Figure 24. P. malariae Schizonts [Lecturer’s PPT]
in terms of treatment it is treated the same way
Feature/s ● 6-12 merozoites, often arranged in a

📋
as P. vivax, by giving Chloroquine
rosette or irregular cluster
Distinguished from P. malariae by size of infected
● Mature schizonts nearly fill the normal-sized
cells and by Schüffner’s dots; less easy to
host RBC
differentiate from P. vivax [2024]
GAMETOCYTES

⭐
C. PLASMODIUM MALARIAE
The plasmodium infection with long-standing nature

⭐
→ Can occur for years
Quartan Malaria
→ Erythrocytic cycle: 72 hours

⭐
● Found in subtropical and temperate areas
Infected cells are normal to smaller in size than most RBCs (old
Figure 25. P. malariae Gametocytes [Lecturer’s PPT]
📋
cells/senescent cells are preferentially infected)
Mnemonics: Malaria = Matanda = Old RBCs [2022] Size of infected ● Reduced size
RBC
Table 4. Morphology of P. malariae
Cytoplasm ● Stains blue; abundant dark pigment may be
RING FORM TROPHOZOITE scattered throughout the cytoplasm
Chromatin ● Pink to red
Other feature/s ● Gametocytes tend to fill the host RBC

⭐ Malignant Tertian or Subtertian or Aestivoautumnal Malaria

D. PLASMODIUM FALCIPARUM

⭐ Erythrocytic cycle: 48 hours

⭐ Deadliest species of Plasmodium
Figure 22. P. malariae Ring-form Trophozoite [Lecturer’s PPT] → Causes 50% of all malarial cases

⭐
Rings ● One chromatin dot and a cytoplasm ring → In the Philippines, causes 75% of severe malaria
thicker than P. falciparum Infects RBCs of ALL stages

📋
● “Bird’s eye” forms may appear → Why it causes the highest degree of parasitemia
Memory tip: Falciparum = walang Finifili [2024]
Size of infected ● Normal to smaller size
⭐
● Found in the tropics, subtropics and Sub Saharan Africa
RBC
Infected cell is the same size as a normal RBC
MATURE TROPHOZOITES → So there is no change in the diameter of the infected RBC vs
normal RBC
● Associated with the development of Burkitt’s lymphoma
Table 5. Morphology of P. falciparum
RING FORM TROPHOZOITE

Figure 26. P. falciparum Ring-form Trophozoite “Headphone type”

[Lecturer’s PPT]
Figure 23. P. malariae Mature Trophozoites [Lecturer’s PPT]
Cytoplasm ● Compact
● May elongate across the host RBC, forming
a “band-form”
● May be oval with a vacuole forming a
“basket-form”
Chromatin ● Rounded
Other feature/s ● Ziemann’s stippling may be present

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 → Presence of immature/mature schizont
in the peripheral blood suggests
hyperparasitemia and has poor
prognosis.
Number of ● 8-24 merozoites
merozoites
Size ● A mature schizont fills 2⁄3 of the infected
RBC
GAMETOCYTES
Figure 27. P. falciparum “Multiply infected RBC” [Lecturer’s PPT]

Figure 31. P. falciparum Gametocytes [Lecturer’s PPT]

Shape ● Crescent or sausage-shaped
Pigment ● Pigment is more coarse and concentrated
Figure 28. Maurer’s clefts in P. falciparum [Lecturer’s PPT]
in the macrogametocyte than the
Rings ● “Headphone type” microgametocytes
● May possess one or two chromatin dots ● Macro = female gametocytes
Size of infected ● No Enlargement ● Micro = male gametocytes
RBC Other features ● Laveran’s bib: remnants of the host RBC
Other features ● May be found on the periphery/edge of the

⭐ Knowlesi/Simian/Quotidian Malaria
RBC (accolé, appliqué) E. PLASMODIUM KNOWLESI
● Maurer’s clefts can be seen in P. falciparum
⭐ Erythrocytic cycle: 24 hours
infections
trophozoites
containing older ring-form
⭐ Quotidian pattern: due to this pattern, may have high levels
→ Resemble the Schuffner’s dots but are of parasitemia leading to severe and may be fatal disease
usually larger and more coarse ● Vector in the Philippines: Anopheles balabacensis and Anopheles
maculatus
DEVELOPING AND OLDER TROPHOZOITES
● Primary malaria of long-tailed macaques and pig-tailed macaques
in Southeast Asia

⭐
→ May affect humans working in the forest

⭐
Infects ALL stages of RBC → can cause severe malaria

⭐
Non-relapsing due to absence of hypnozoite stage
Microscopically indistinguishable from P. malariae
→ PCR can distinguish between them
● Anyone with a severe and rapidly deteriorating condition should
be treated aggressively and urgently

💬
● Responds to Chloroquine and Primaquine
Figure 29. P. falciparum developing & older trophozoites [Lecturer’s PPT] There is so much similarity between knowlesi and falciparum, so if
there is doubt, go ahead and treat as falciparum
Shape ● Remain in ring form, but may become
thicker and more compact Table 6. Morphology of P. knowlesi
Pigment and ● Amount of pigment and chromatin may also RING FORM TROPHOZOITE
chromatin increase
SCHIZONTS

Figure 30. P. falciparum Schizonts [Lecturer’s PPT] Figure 32. P. knowlesi Ring-form trophozoite [Lecturer’s PPT]
Location in the ● Schizogony does NOT take place in the Rings ● Rings may show double chromatin dots
body peripheral blood but in capillaries of ● Appliqué forms may be seen as well as
organs and muscles rectangular rings harboring one or more
accessory chromatin dots
Size ● 0.75x (smaller)
Other Features ● RBC may also be multiply infected

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 DEVELOPING AND OLDER TROPHOZOITES

Figure 33. P. knowlesi Developing and older trophozoites [Lecturer’s PPT]

Band forms ● Band forms may appear that are similar in
appearance to P. malariae
Stippling ● Stipplings appear called Sinton and Mulligan’s

⭐Figure 35. Malaria species in humans

stippling
[Lecturer’s PPT]
SCHIZONTS
📋MUST KNOW [2024]

● Mnemonics
→ Morphology
◼ RBC predilection:
– Vivax = Vata (Young)
– Malariae = Matanda (Old/Senescent)
– Falciparum = Walang Finifili (All stages)
◼ Effect to RBC: Opposite to the RBC predilection
Figure 33. P. knowlesi Schizonts[Lecture PPT]
– Vivax = Young RBCs = Enlarged
Number of ● Contains an average of 10 merozoites – Malariae = Old RBCs = Smaller (or normal)
Merozoites – Falciparum = All stages = Normal
Stippling ● Sinton and Mulligan’s stippling may be ◼ RBC stipplings
observed – Vilma Santos = Vivax: Schuffner’s dots
GAMETOCYTES – Orange Shake = Ovale: Schuffner’s dots
– Manila Zoo = Malariae: Ziemann’s dots
– Ferdinand Marcos = Falciparum: Maurer’s clefts/dots

IV. PATHOGENICITY AND VIRULENCE

Figure 34. P. knowlesi Gametocyte [Lecturer’s PPT]

Shape and SIze ● Macrogametocytes: spherical and fill the host
RBC
● Microgametocyte: smaller than the
macrogametocyte

Pigment ● Macrogametocytes: cytoplasm stains blue,

eccentric nucleus stains red
● Microgametocyte: cytoplasm usually stains
pale pink, nucleus stains darker red

Figure 36. Pathogenicity and virulence in malaria [Lecturer’s PPT]

● The pathological process in malaria is the result of the
erythrocytic cycle.
→ Produces the signs and symptoms of malaria

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 ● Hepatosplenomegaly
→ Develops due to the lysis of cells, phagocytosis of cell
remnants and debris, and congestion of the Kupffer cells of
the liver by hemozoin and can lead to tears of the splenic
capsule or spleen rupture due to trauma or coughing, and
may require surgery
→ Splenic enlargement in children 2-9 years old serve as a
useful index of the prevalence of malaria
◼ Largest spleen is found in P. vivax infection
◼ Smallest spleen is found in P. malariae
● Anemia

Figure 37. Erythrocytic cycle in malaria [Lecturer’s PPT]

● The following event happens:
→ Hemolysis
→ Liberation of metabolites
◼ Stimulation of cytokines resulting from the immune
response to the antigen of the malarial parasite
→ Immunologic response of the host to the antigenic
material
→ Formation of malarial pigment
A. VIRULENCE Figure 38. Anemia in malaria [Lecturer’s PPT]
● Erythrocytic cycle → Repeated attacks of malaria produces anemia because
→ RBC invasion by merozoites induces changes in cytoskeleton non-infected RBCs are also sensitized and destroyed due to
and decreases deformability of RBC antibodies to the RBC
→ Hemozoin formation depletes iron stores-anemia
⭐
● Knobs develop for adhesion
Most adhesive protein: P. falciparum erythrocyte ● Immune complexes are formed and may be deposited in the
membrane protein 1 (PfEMP1) kidney
◼ Seen in P. falciparum infections ● Severity of complications and mortality increase as the level of
→ Histidine-rich proteins (HRP) − Localize to the parasitemia increases
→ P. vivax and P. ovale invade reticulocytes & P. malariae
⭐
cytoadherence ligands making the adhesion more effective
Rosetting cytoadherence by P. falciparum causes plugging invade senescent cells
of small vessels by large number of parasitized RBCs and → Infection with these 3 parasites (Vivax, Ovale, and Malariae)
RBCs sticking to the endothelium of vessels limits the number of RBCs that can be parasitized to less than
◼ This causes ischemia of organs including the brain, 3% of all erythrocytes.
→ P. falciparum and P. knowlesi invade all ages of RBC
⭐
kidney, heart, lungs, and GIT
Antigens of P. falciparum induces cytokines which stimulate the ◼ Infection by this parasites result in early considerable
release of Tumor Necrosis Factor (TNF) or Cachexin responsible anemia
in the development of fever, paroxysms, hemagglutination, ◼ P. falciparum alters RBC viscosity, causing
pains, and prostration obstruction and end-organ ischemia.
→ TNF also produces neurologic symptoms which play a role ● Severity of complications and mortality increase as the level

📖
in cerebral malaria of parasitemia increases
Malaria in pregnancy increases the risk of: [Belizario, 2013]
B. PATHOGENICITY
→ Maternal death
● Increased capillary permeability allows fluid to leak into → Maternal anemia
surrounding tissues and cause congestion resulting to tissue → Intrauterine growth retardation
infarction and necrosis causing obstruction or sludging of RBCs → Spontaneous abortion
in the capillaries → Stillbirth
● Hemozoin formation
📖
→ Low birth weight
→ Comes from the digestion of hemoglobin in the infected RBC Non-immune pregnant women are susceptible to all complications
and gets deposited to various organs causing depletion of associated with severe malaria such as cerebral malaria,
iron stores and anemia
📖
hypoglycemia, and pulmonary edema [Belizario, 2013]
● Rupture of RBCs causing malarial paroxysms In severe forms of malaria, impairment of consciousness and
→ Released hemosiderin granules that accumulates in the liver, other signs of cerebral dysfunction, such as delirium and
spleen, and other organs resulting to black discoloration
📖
generalized convulsions, are commonly observed. [Belizario, 2013]
→ Lysis of cells and phagocytosis of cell remnants, debris, and Other signs and symptoms [Belizario, 2013]
hemozoin congests the Kupffer cells of the liver resulting in → Cerebral malaria with diffuse symmetric encephalopathy
hepatosplenomegaly. → Retinal hemorrhage
→ Bruxism (fixed jaw closure and teeth grinding)
→ Mild neck stiffness
PARA LEC | LE3 - 01 Malaria PAGE 9 of 22
📖 Pouting or a pout reflex may be elicited by stroking the sides of ● Ranges from 9 days to 3 years depending on the dose of

📖 Respiratory findings are also a major feature of severe malaria.

[Belizario, 2013]
the mouth
Altered pulmonary function is common, and it includes airflow
obstruction, impaired ventilation and gas transfer, and increased
sporozoites inoculated, the parasite strain, the immune status of
the host, and host malaria chemoprophylaxis history
→ Those coming from endemic areas have partial immunity,
they can be bitten by infected mosquitoes but they don't

📖
pulmonary phagocytic activity. [Belizario, 2013]
In African children, pneumonitis from sequestered,
parasitized RBC and inflammatory cells are seen in
postmortem pulmonary vasculature, while in adults,
non-cardiogenic pulmonary edema and acute pulmonary
manifest any clinical symptoms.
◼ However, uprooting this individual to an endemic area to
Manila, the individual loses the immunity due to immunity
resulting from the every so often biting of the infected
female mosquito

📖
distress syndrome (ARDS) may be observed. [Belizario, 2013] ● There are no absolute clinical features of malaria except for
The cytoadherence, rosette formation, and sequestration of regular paroxysms of fever with associated asymptomatic
parasitized erythrocytes lead to a decrease in tissue perfusion intervals.

📖
resulting in decreased renal blood flow. [Belizario, 2013]

⭐ Seen in all species

C. PRODROMAL SYMPTOMS
The increase of TNF in tubular epithelial cells leads to
inflammatory cell infiltration in the interstitium and altered tubular
● Period after incubation
transport, which result in tubular damage and dysfunction.
● Weakness, exhaustion, body pains, loss of appetite, nausea,
📖 The presence of GP1 and other Falciparum malaria antigens
[Belizario, 2013]
vomiting, and chills
● Symptoms are malaise, backache, diarrhea, and abdominal
lead to release of cytokines and mediators that decrease the

📋
discomfort
systemic vascular resistance and increase renal vascular
Be cautious in establishing a diagnosis and consider this in
resistance. All these changes eventually lead to acute tubular
making a differential diagnosis with acute viral hepatitis every
📖
necrosis causing acute renal failure. [Belizario, 2013]

📋
time to not miss a possible case of malaria. [2024]
The most common complications of severe malaria in children
Make sure you do not treat acute viral hepatitis as the
are cerebral malaria, severe anemia, respiratory distress, and
definitive diagnosis in cases of malaria. This is called a red
hypoglycemia. [Belizario, 2013]
herring, when you mistake a diagnosis for a specific
→ Children with severe malaria, most commonly present with
diagnosis. [2024]
seizures. These convulsions are common before or after the
onset of coma and are significantly associated with VI. STAGES OF MALARIA PAROXYSMS

📖
neurologic sequelae. Table 9. Stages of Malaria Paroxysms
The clinical indicators of poor prognosis include deep coma, Stage Symptoms Duration
absence of corneal light reflex, respiratory distress (acidosis),
● Sudden feeling of coldness,
circulatory collapse, decerebrate or decorticate rigidity,
shivering, intense peripheral Rigors last from
opisthotonos, and age below 3 years. [Belizario, 2013]
vasoconstriction 15-60 minutes
V. CLINICAL MANIFESTATIONS OF MALARIA Cold stage
● Patients may vomit and febrile then shivering
A. PREPATENT PERIOD convulsions may ensue in stops
● Clinical manifestations will start with non-specific symptoms like young children
headache, muscle pains, nausea, vomiting, loss of appetite, and
● Fever, headache, palpitations,
fever
thirst, nausea, and vomiting
● Time between sporozoite injection to detection of parasites in the
Hots stage ● Temperature may reach up to

⭐
blood
/ Flush 41°C or more 2-6 hours
2-4 weeks in general
stage ● The patient may become
Table 7. Pre-patent period of Malaria
delirious and confused
Parasite Duration ● Skin is flushed and hot
P. falciparum 11-14 days ● Defervescence, diaphoresis, Temperature
Sweating
P. vivax 11-15 days profuse sweating ensues goes down 2-4
stage
● Other symptoms diminish hours
P. ovale 14-26 days
● The total duration of an attack is 8-12 hours
P. malariae 3-4 weeks ● The classic periodicity of attacks occurs only if the patient is left
P. knowlesi 9-12 days untreated until such time when the life cycle phases become
synchronized and sufficient numbers of RBC containing schizonts
B. INCUBATION PERIOD rupture at about the same time
● Time between sporozoite injection and the appearance of clinical → Initially, fever may be irregular before developing periodicity

⭐
symptoms
8-40 days typically
Table 8. Incubation period of Malaria
Parasite Duration
P. falciparum 8-15 days
P. vivax 12-20 days
P. ovale 11-16 days
P. malariae 18-40 days
P. knowlesi 5 days - few week

PARA LEC | LE3 - 01 Malaria PAGE 10 of 22

 VII. COMPLICATIONS OF MALARIA INFECTION
● P. vivax, P. ovale, and Quartan Malaria are relatively benign
→ P. vivax and P. ovale only infect young RBCs
→ P. malariae infects the aging cells which limit the RBCs that
they can parasitize to less than 3% of all RBCs
● The complications that arise are due to pre-existing debilitating

⭐
illnesses or intercurrent diseases
P. falciparum and P. knowlesi Malaria are more complicated
because all stages of RBCs are infected.
→ Also, the erythrocytic cycle of P. knowlesi is 24 hours
(frequent malarial paroxysms)
● The course of the severity of the attack of malaria depends on
the species and the strain of the infecting parasite
→ It also depends on depends on the age, genetic constitution,
immunity, general health, and use of chemoprophylaxis
● Initial symptoms of malaria are atypical and difficult to recognize,
but within hours life-threatening complications may start to occur

⭐
(within 12 hours)
Falciparum malaria in young children is considered a
medical emergency for it can be rapidly fatal
● Children with severe malaria commonly experiences seizures
→ These convulsions are common before or the after the onset
of coma and are commonly associated with neurologic
sequelae
Figure 39. Typical temperature charts of different Plasmodium ● Children from Sub-saharan Africa
species [Lecturer’s PPT] ● Other common complications of severe malaria in children
● The interval between attacks is determined by the length of the include:
erythrocytic cycle → Severe anemia
→ P. falciparum, P. ovale, P. vivax - 48 hours (every two days) → Respiratory distress
→ P. malariae - 72 hours (Every three days) → Hypoglycemia
→ P. knowlesi - 24 hours (Quotidian pattern / non-relapsing)
(Everyday) 📋A. COMPLICATIONS OF P. KNOWLESI [2024]

◼ Does not have an exoerythrocytic stage ● Severe thrombocytopenia, jaundice, deranged liver enzymes
● Acute respiratory distress syndrome with tachypnea, hypoxemia,
A. RECRUDESCENCE VS RELAPSE and pulmonary infiltrates on CXR
● Recrudescence ● Acute Renal Failure with elevated serum creatinine
→ The renewal of parasitemia or clinical features arising from
⭐
● Hypotension
persistent undetectable asexual parasitemia in the absence Acidosis
of exoerythrocytic cycle → Occurs due to lactate in the circulation, compounded by an
● Relapse acute renal failure
→ Renewed asexual parasitemia following a period in which the → Lactate gets converted to lactic acid so the patient can go into
blood contains no detectable parasites lactic acidosis
→ Occur with Vivax and Ovale malaria from reactivation of
📋B. COMPLICATIONS OF P. MALARIAE
⭐ Nephrotic syndrome
[2024]
hypnozoite forms of the parasite in the liver
◼ Cold, fatigue, trauma, pregnancy, and intercurrent
falciparum malaria may precipitate reactivation → Chronic P. malariae infections in children may result in
immune-complex deposition on the glomerular walls

💬 Mnemonic: “FALCIPARUM”
C. COMPLICATIONS OF P. FALCIPARUM

● Fever (Blackwater fever)

● ARDS
● Low blood sugar / hypoglycemia
→ Consumption of the patient’s blood sugar by the parasite
→ Especially if the patient is on Quinidine
● Cerebral malaria
Figure 40. Recrudescence and Relapse [Lecturer’s PPT]
● Infections / secondary infections / sepsis
📋CONCEPT CHECKPOINT [2025] → Gram-negative infections because of the lower resistance
and medical procedures that you do to patients with
1. T/F. Histidine-Rich Pr (HRP) is the most adhesive protein among
Falciparum malaria that predisposes them to infections such
the knobs.
as pneumonia, pulmonary congestion, and bacteremia
2. What do you call the pigment that forms when hemoglobin is
● Pulmonary edema
digested? How is this pathogenic?
Answers:
● Anemia
1. F. Most adhesive is PfEMP1 → Because of the hemolysis
2. Hemozoin ● Renal failure secondary to Acute Tubular Necrosis or Acute
Kidney Injury

PARA LEC | LE3 - 01 Malaria PAGE 11 of 22

 → Emergency dialysis must be done to restore normal renal ● At times, the liver is enlarged and tender, the skin is icteric, and
function the urine contains bile
●
●
Urine output would decrease secondary to AKI
Metabolic acidosis
📋
ALGID MALARIA [2024]
● Falciparum malaria attacks characterized by the rapid
→ Due to increase in hydrogen ions, especially in lactic acidosis
development of hypotension and impairment of vascular

💬 Massive hemolysis of RBCs and release of free hemoglobin

FEVER (BLACKWATER)
which finds its way to the urine leading to hemoglobinuria
● Can lead to renal insufficiency or renal failure
● Occurs almost exclusively in patients suffering from severe
falciparum malaria but has been reported in P. vivax and quartan
malaria as well
● Can also be due to Quinine therapy and malaria during
pregnancy
● Quinine therapy should NOT be discontinued if blackwater fever
perfusion
● Temperature falls rapidly, and the patient may become delirious
● Symptoms of generalized vascular collapse and shock develop
quickly
● May be the result of gram-negative septicemia, pulmonary
edema, massive gastrointestinal hemorrhage, splenic rupture, or
uncorrected dehydration
● Initial therapy involves correction of the hemodynamic problems
and administration of antibiotics

⭐Table 10. Poor Prognosis of Falciparum Malaria

POOR PROGNOSIS OF FALCIPARUM MALARIA
develops

💬 Anoxia of the brain because of the obstruction of the tiny blood

CEREBRAL MALARIA Laboratory Findings Clinical Findings
● Hyperparasitemia
vessels which supply blood to the brain
→ >250,000/ μL or >5% of ● Deep coma
● In severe malaria, impairment of consciousness and other
infected RBCs using the ● (-) corneal light reflex
signs of cerebral dysfunction such as delirium, and generalized
malaria blood smear ● Respiratory distress that
💬
convulsions are commonly observed
The neurological symptoms once promptly and adequately ● (+) Mature & immature leads to Acidosis
treated are reversible, and the majority of the patients make a schizonts in PBS ● Circulatory collapse
complete recovery → Phenomenal observation (hypotension)
● It is essential to do a lumbar puncture on the patient in Falciparum malaria ● Opisthotonos
● Cerebral malaria generally manifests with diffuse symmetric → Should not be seen in ● Age < 3 years old
encephalopathy. Symptoms may also include retinal PBS
hemorrhage, bruxism, and mild neck stiffness

📖 Falciparum malaria in young children is considered a medical

● If left untreated, may progress to persistent coma and death
ACUTE RENAL FAILURE
● Occurs in 60% of patients with severe malaria
● Acute tubular necrosis and Acute renal failure results from tubular
damage and dysfunction by inflammatory cell infiltration, and
decreased tissue perfusion from plugging of parasitized RBCs to
D. SEVERE MALARIA IN CHILDREN
emergency for it can be rapidly fatal [Belizario, 2013]
● Initial symptoms may be typical and difficult to recognize. But
within hours, life threatening complications may start to occur
→ Expect that within 12 hours, Falciparum malaria may already
deteriorate and develop the complications

💬
renal blood flow ● Most common complications of severe malaria in children
Urine output decreases → Cerebral malaria
● Patients present with elevated creatinine levels → Severe anemia
● Treatment: hemodialysis and exchange blood transfusion → Respiratory distress

💬
RESPIRATORY FINDINGS IN MALARIA → Hypoglycemia
Children with malaria commonly experience seizures
💬
● Respiratory findings are also a major feature of Severe Malaria
→ Convulsion is common before or after the onset of coma and
Altered pulmonary function is common with airflow obstruction;

💬
are significantly associated with neurologic sequelae
the lungs are affected with their blood supply

📖
2 million children died due to malaria from Sub-saharan Africa
● There is impaired gas exchange
10% of children who survive cerebral malaria will develop
● Children - pneumonitis from sequestered parasitized RBC and
sequelae such as hemiparesis, cerebellar ataxia, speech
inflammatory cells
disorders, generalized spasticity, or some behavioral disturbances
💬
● Adults - pulmonary edema and ARDS (>80% mortality rate) [Belizario, 2013]
Factors that predispose to pulmonary edema include
hyperparasitemia, renal failure, and pregnancy
ANEMIA
● Consequence of the heavy parasite load
● Should be treated with transfusion to correct hemoglobin and
hematocrit because the patient can go into congestive heart
failure if not
● Should be treated with due care to prevent fluid overload and
overt pulmonary edema
📋
DYSENTERIC MALARIA [2024]
● Described as abdominal pain, nausea, vomiting, and upper
gastrointestinal bleeding, which may be related to focal ischemic
changes in the intestinal wall capillary bed
Figure 41. Comparison of signs and symptoms of severe malaria in
● Seen in patients from endemic areas
adults and children [Belizario, 2013]

PARA LEC | LE3 - 01 Malaria PAGE 12 of 22

 E. OTHER COMPLICATIONS IN SEVERE MALARIA → Specimens can be taken anytime since infections are not so
highly synchronized
● Late development of stages of parasite can be demonstrated in
repeated smears every 4-6 hours if a high degree of synchrony
exists (Note: In Belizario and upper trans: every 4-6 hours while in

💬
the asynchronous lecture: every 6-8 hours is usually appropriate.)
Late stages cannot be seen in Falciparum malaria
● Repeated testing for several days is recommended if parasites

💬
are not found initially
High index of suspicion that there is a malarial infection, then
given an empiric therapy for malaria

💬
Figure 42. Other complications of severe malaria [Belizario, 2013] ● Blood smears can also be used to monitor response to treatment.
● Hemolytic anemia Follow up blood smears are needed to detect if there is a

💬
● Hypoglycemia reduction of parasitemia in subsequent blood smears
● Hemoglobinuria Continued monitoring should be implied until there is a

📖
● Blackwater fever clearance of parasitemia

⭐
→ Secondary to massive intravascular hemolysis In individuals who are not seriously ill, monitoring once daily
5 species that are medically important to humans: is sufficient. Seriously ill patients should be monitored two to

💬
→ Plasmodium falciparum: Causes most serious disease ; three times daily [Belizario, 2013]
disease of the tropics Some of the medical personnel in the Philippines do not
→ Plasmodium vivax: Most widely distributed; most common follow up after giving a treatment
type in all endemic areas ● Malaria Rapid Diagnostic Test
→ Plasmodium ovale: disease of the tropics → Uses immunochromatography to detect Plasmodium

📖
→ Plasmodium malariae specific antigens in a finger-prick blood sample
→ Plasmodium knowlesi Can be easily taught to village health workers and the results

📖
◼ Still not very well studied
◼ Recently been discovered in humans in the Philippines
and most Southeast Asia
◼ This is normally a monkey parasite, long tailed macaques
have apparently found its way to infect humans.
◼ Life cycle is microscopically
● Most common combination is P. vivax and P. falciparum
VIII. DIAGNOSIS OF MALARIA
● Prompt and adequate diagnosis of malaria is necessary to
→ Not locally available
prevent life-threatening complications
● Important to suspect malaria at the onset and history of travel to
can likewise be easily interpreted [Belizario, 2013]
Main disadvantages compared to microscopy [Belizario, 2013]
◼ Lack of sensitivity at low parasitemia
◼ Inability to quantify parasite density
◼ Inability to distinguish among P. vivax, P. ovale, and P.
malariae, as well as sexual and asexual stages
◼ Persistent positive test despite parasite clearance
following chemotherapy
◼ Higher cost
◼ Mainly for research purposes

📖
→ Antigens detected: Histidine Rich Protein II (HRP II)
an endemic area
Water soluble protein that is produced by trophozoites
● Initial symptoms are nonspecific and not reliable in clinching the
and young gametocytes of P. falciparum [Belizario, 2013]
diagnosis, even if malaria can present with classic paroxysmal
● Plasmodium Lactate Dehydrogenase (pLDH)
fever and symptomatic intervals
→ Do not disregard as flu or as viral hepatitis
A. LABORATORY TESTS
● Thin or thick blood smears with Giemsa and Wright stain

⭐
→ Perform both thick and thin blood smear
Thick film
◼ Reveal parasites if present

⭐
◼ The most efficient method of detecting malarial parasites
Thin film
◼ Identification of species
◼ Stages found in thin smears:
– Ring forms (Early trophozoites)
– Late trophozoites (older ring stage)
– Schizont
– Gametocytes (macrogametocytes = female; Figure 43. Principle of Plasmodium Lactate Dehydrogenase Testing
[Lecturer’s PPT]

📖
microgametocytes = male)

Obtaining smears every 6 to 8 hours is usually appropriate.
This may have to be continued until a diagnosis of malaria is
made or until malaria can be confidently ruled out [Belizario, 2013]
→ Used for microscopic identification of malarial parasites
→ GOLD STANDARD in making the definitive diagnosis
→ Presence of ring forms or the trophozoites developing inside
💬
infected RBCs
Giemsa stain allows the visualization of certain structures
like Maurer’s cleft
PARA LEC | LE3 - 01 Malaria
📖
→ Produced by sexual and asexual stages
Can be used to distinguish between Falciparum and
Non-Falciparum but not among the non-P. falciparum[Belizario,
2013]
→ Highly sensitive for the diagnosis of severe malaria
→ A major target in the diagnosis of erythrocytic stages of
malarial parasites because it is highly expressed during
blood-stage parasites and highly distinguishable from human
LDH
→ Not readily available
PAGE 13 of 22
● Plasmodium Aldolase
→ Aldolase: a major enzyme involved the glycolytic cycle of
Plasmodium and is released into the blood during infection
→ Expressed by all stages of all Plasmodium species
→ PMA (Pan Malarial Antigen)
◼ Aldolase combined with HRP II in a single kit with >90%
specificity can be performed in 30 minutes without the
use of electricity or special equipment
→ Not readily available
📖
● Serologic tests:
Cannot differentiate between current and past infections and
are therefore helpful in epidemiologic studies [Belizario, 2013]
→ Indirect Hemagglutination (IHA) & Indirect Fluorescent
Antibody test (IFAT)
◼ Can be used for patients with chronic malaria or patients
with hepatosplenomegaly that cannot be explained by
other causes
◼ No longer available
→ ELISA
◼ Cannot differentiate between past infection from current
infection
◼ Most helpful in epidemiologic studies
● PCR in Malaria:
→ Used in cases of low parasitemia or in mixed infections
→ Can be used to differentiate P. malaria from P. knowlesi
📖
IX. TREATMENT OF MALARIA
Classification of drugs: [Belizario, 2013]
→ Causal prophylactic drugs
◼ Prevent the establishment of the parasite in the liver
→ Blood schizonticidal drugs
◼ Attack the parasite in the RBC, preventing or terminating
📖
the clinical attack
The main uses of antimalarial drugs are: [Belizario, 2013]
→ Protective (prophylactic)
◼ Used before the infection occurs or before it becomes
evident
◼ Aims to prevent either the occurrence of the infection or
any of its symptoms
→ Curative (Therapeutic)
◼ Action on the established infection, which involves the
use of blood schizonticidal drugs for the treatment of
the acute attack and in the case of relapsing malaria,
radical treatment of the dormant liver forms
→ Preventive
◼ Prevention of transmission
◼ Use of gametocytocidal drugs to attack the
gametocytes in the blood of the human host
● Chloroquine is no longer of use in the treatment of P. falciparum
→ In certain areas, there is also resistance to chloroquine by P.
vivax
[Lecturer’s PPT]
Figure 44. Antimalarial Agents and Targeted Phases
PARA LEC | LE3 - 01 Malaria
● Antimalarial drugs have selected actions on the different phases
of the life cycle of the malarial parasites.
→ There are certain antimalarial drugs which can be
schizonticides and others.
A. MEDICATIONS IN TREATING MALARIA
Figure 45. Antimalarial Drugs with Classifications [Lecturer’s PPT]
● Multidrug-resistant malaria is considered when treatment failure
occurs with three or more malarial drugs
● Chloroquine was the mainstay of malarial treatment for the last 50
years
● The DOH Malaria Program recommends the use of
Artemisinin-based combination therapies (ACTs) for severe and
uncomplicated Falciparum malaria because of the emergence of
multidrug resistance (MDR) strains
BLOOD SCHIZONTICIDES
● Used for clinical cure of acute attack of malaria
● Most have no effect on either pre-erythrocytic stages of the
parasite or gametocytes
→ Important to hit on the erythrocytic stage so that the
schizonticides destroy the developmental stages in the liver
● More effective and life-saving compared to tissue schizonticides
● Examples:
→ Quinine
◼ Effective against all five species of human malarial
parasite
◼ Effective but difficult to obtain
◼ SEs: Tinnitus, headache and vertigo
→ Quinidine
◼ May be an alternative to quinine if it is not available
◼ Should be instituted with proper dosage and patients
should be in electrocardiographic monitoring because of
QT prolongation
◼ More effective than Quinine
→ Chloroquine
◼ Useful for non-Falciparum species of malaria
◼ In treating malaria with Chloroquine, it is important to
determine the area where there is chloroquine resistance
or sensitivity
◼ It is still effective in the Philippines against P. vivax
→ Amodiaquine
◼ Not extensively used because of certain SEs
→ Mefloquine
◼ Effective against both chloroquine-sensitive and
chloroquine-resistant strains of P. falciparum and P.
vivax
– There have been a series of reports in Thailand to have
shown resistance against Mefloquine
◼ Also used as a chemoprophylaxis against malaria
PAGE 14 of 22
 – There are still second thoughts in giving mefloquine as ◼ Primaquine is used as a prophylaxis for the development
a chemoprophylactic drug due to the reports of of gametocytes
resistance
C. UNCOMPLICATED P. VIVAX OR P. OVALE
◼ Also effective against P. malariae and P. ovale and used
● Children and Adult
as a prophylactic agent
→ 1st line: Chloroquine + Primaquine
→ Doxycycline
→ 2nd line: AL + Primaquine
◼ Good chemoprophylactic drug on a short term notice
● Primaquine is always a present medication because we would
◼ E.g: If you go to an endemic area (Palawan, Quezon,
want to destroy the development of schizoids in the liver
etc.) and you’re leaving in 1 - 2 days, you are given
Doxycycline 100 mg OD on a full stomach D. CHEMOPROPHYLAXIS
– You are advised to continue taking the drug as you
arrive in the endemic area and as you leave, extend
taking it for 4 weeks / 1 month
◼ SEs: Photophobia and vaginitis in women
→ Proguanil
◼ Prevents the development of oocyst in the mosquito
(Sporonticidal)
→ Halofantrine
◼ Eradicated and withdrawn from the market because of
certain cardiac SEs
→ Artemisinin
◼ Relatively new and is derived from Qinghaosu, a Chinese
discovery
◼ Effective against P. falciparum, P. knowlesi, P. vivax and
in patients with cerebral malaria Figure 46. Medication Guide for Chemoprophylaxis [Lecture PPT]
◼ Available in the Philippines as Artemether-lumefantrine ● May be protective to travelers who have no immunity to malaria
(Coartem) in oral form → Can only suppress the symptoms of malaria
– 4 tablets for 6 doses every day for each course → Travelers are advised to carry Sulfadoxine and
◼ IV form is not yet available but is better than the oral form Pyrimethamine (Fansidar)
– Useful for patients who may be vomiting and may not → Prophylactic drugs should be taken with good compliance for
be able to tolerate oral tablets the duration of the stay and contingent 4 weeks after
◼ If this is not available, resort to Quinine infusion for a exposure to infection since parasites can still emerge from
certain period of days with appropriate dosage and the liver after this period
intervals until such time that the patient is able to tolerate ◼ Exception: Atovaquone + Proguanil can be stopped after
oral tablets
📖
one week (replacement for mefloquine)
TISSUE SCHIZONTICIDES Those traveling to areas with exclusive P. vivax malaria or with
● Destroys the pre-erythrocytic stages in the liver low-risk of Chloroquine resistance [Belizario, 2013]
● Primaquine → Chloroquine
→ Effective against hypnozoites of P. vivax and P. ovale ● Those traveling to areas with high-risk of Chloroquine resistance
(hypnozoitocidal or antirelapse drugs) should use the following:
● Recall that P. vivax and P. ovale have hypnozoite stages (latent → Mefloquine
stages) in the liver, so for the completion of therapy (after giving → Doxycycline

📖
your Chloroquine) it is important to follow this up with Primaquine → Atovaquone + Proguanil
to destroy the tissue schizonticides that develop within the liver Those who are pregnant: [Belizario, 2013]
due to the presence of latent P. vivax or P. ovale → Use of insecticide treated nets
→ Application of intermittent preventive treatment
GAMETOCYTICIDES ◼ Providing at least two preventive treatments of an
● Current guidelines also recommend the use of gametocyticides to effective antimalarial drug
reduce transmission
● Primaquine E. MALARIA PREVENTION TOOLS
→ Gametocytocidal for all five species of malaria parasites ● Screens in windows and air-conditioned housing are less likely to

📖
→ Acts to render the patient noninfectious to mosquitos be exposed to malaria
● Derivatives from Artemisinins Use of insecticide treated nets with Permethrin or Deltamethrin
[Belizario, 2013]
→ Artemether
→ Sodium artesunate → Major vector control strategy paired with indoor residual
spraying
B. UNCOMPLICATED P. FALCIPARUM OR P. MALARIAE ◼ The latter being used in epidemics, areas with stable
● Children and Adult transmission but without reduction of malaria incidence,
→ 1st line: Artemether-lumefantrine (AL) + Primaquine and areas of displaced populations
● Adult:
📖
● Use light-colored clothes that cover most of the body
→ 2nd line: Quinine sulfate + Clindamycin (for pregnant Use of insect repellents with any of the ff: [Belizario, 2013]
patients) → 35% DEET (N,N-diethyl-m-toluamide) as lotion
→ 2nd line: Tetracycline or Doxycycline + Primaquine (for → Pyrethrum as insect spray
non-pregnant patients) → Permethrin as repellant spray
◼ Doxycycline is contraindicated to pregnant women (SE: ● Going home before dusk take place
yellowing of the teeth of the fetus)

PARA LEC | LE3 - 01 Malaria PAGE 15 of 22

 X. SAMPLE QUESTIONS b) Age <3 years
1. Along with the appropriate anti-falciparum drug, why is c) Pregnancy in endemic area
Primaquine given to patients with P. falciparum? d) Low serum bicarbonate (HCO3)
a) To destroy the gametocytes to restrain initiation of life cycle of
the parasite 12. Which of the following conditions in severe malaria may
b) To prevent asexual reproduction in the RBC develop shock from supervening bacterial septicemia?
c) To stop cytoadherence a) Acute Respiratory Distress Syndrome
d) To eradicate the repeated Exoerythrocytic phase b) Acute tubular necrosis
c) Algid malaria
2. Which of the following blood smear findings is the BEST d) Blackwater fever
indicator for diagnosis of Falciparum malaria?
a) Absence of mature trophozoites 13. What type of cycle does P. malariae produce?
b) Parasitemia of >5% of RBCs a) Benign Tertian
c) Presence of gametocytes b) Quotidian
d) Appearance of early ring forms c) Malignant Tertian
d) Quartan
3. Which of the following populations is MOST vulnerable to the
severe disease of malaria? 14. Which of the following cytokines is responsible for fever and
a) Non-immune individuals paroxysms and plays a role in cerebral malaria caused by P.
b) People living on malaria endemic areas falciparum?
c) Pregnant patients a) Interferon alpha
d) Children b) Interleukin 12 (IL 12)
c) Tumor necrosis factor (TNF)
4. Which of the following cases of malaria requires in-patient d) Interleukin 6 (IL 6)
care?
a) P. vivax 15. What developmental stage of P. vivax is responsible for
b) P. ovale relapse?
c) P. falciparum a) Sporozoite
d) P. malariae b) Hypnozoite
c) Merozoite
5. Which of the following reasons justifies the use of d) Gametocyte
maintenance IV Fluids with glucose in Falciparum malaria?
a) Parasitemia, malaria 1. A. Primaquine is a gametocidal agent in falciparum malaria. Gametocytocidal for
all five species of malaria parasites. Acts to render the patient noninfectious to
b) Pulmonary edema mosquitoes.
c) Hypoglycemia 2. B. Hyperparasitemia: >250,00/μL or >5% of infected RBCs using the malaria
d) Cerebral malaria blood smear indicates poor prognosis of falciparum malaria
3. A. Individuals with little to no immunity against the disease are the most
vulnerable to the severe disease of malaria compared to those coming from
6. In which of the following malarial infections is it essential to
endemic areas who have partial immunity because they can be bitten by infected
have early identification and aggressive treatment, mosquitoes but don’t manifest any clinical symptoms. However, uprooting this
particularly in a non-immune person? individual from an endemic area to a non-endemic area will allow them to lose
a) P. malariae their immunity.
4. C. Among all the malarial species, P. falciparum remains to be the most fatal thus
b) P. falciparum
requires intensive in-patient care.
c) P. vivax 5. C. Hypoglycemia or low blood sugar can develop in infections caused by P.
falciparum since the parasite consumes the patient’s blood sugar. Thus,
7. [T/F] The initial symptoms of malaria are non-specific. replacement via IV fluids with glucose is necessary.
6. B. Among all the malarial species, P. falciparum remains to be the most fatal thus
initial identification and prompt aggressive treatment is necessary particularly in a
8. [T/F] Thin film is COMMONLY used to determine the species non-immune person.
of malarial parasite. 7. T. The initial Cold Stage starts with a sudden feeling of coldness, shivering,
intense peripheral vasoconstriction. Patients may vomit; Febrile convulsions may
9. What is the microscopic appearance on stained blood smear ensue in young children
8. T. Thick film, on the other hand, is used to detect the presence of a malarial
of this pathognomonic characteristic of Falciparum malaria?
parasite.
a) Ring trophozoites 9. B. Seen only in P. falciparum.
b) Banana-shaped gametocytes 10. C. Anopheles transmits malaria.
c) Band-shaped trophozoites 11. C. In low transmission areas, severe malaria is particularly likely and dangerous
in pregnancy.
d) Schuffner’s dot in infected RBC
12. C. Algid malaria may be a result of gram-negative septicemia. Its presentation
manifests as delirium, hypotension from generalized vascular collapse, and
10. Which of the following vectors transmits malaria? shock.
a) Aedes 13. D. Recall. The plasmodium infection with long-standing nature.
b) Mansonia 14. C. Antigens of P. falciparum induces cytokines which stimulate the release of
Tumor Necrosis Factor (TNF) or Cachexin responsible in the development of
c) Anopheles fever, paroxysms, hemagglutination, pains, and prostration.
d) Culex 15. B. P. vivax has a persistent/dormant stage (Hypnozoite) in the liver which is the
cause of relapse.
11. The following are poor prognostic signs of severe
Falciparum malaria EXCEPT: XI. REFERENCES
a) Respiratory distress [1] Europa, D. (2023). Malarial Parasites [Lecture PPT]

PARA LEC | LE3 - 01 Malaria PAGE 16 of 22

[2] Belizario, V.Y., & De Leon, W.U. (2013). Medical Parasitology in
the Philippines. Diliman, Quezon City: The University of the Philippine
Press. Pp. 85-106
[3] 2025 Trans
[4] 2024 Trans

XII. APPENDIX

Figure 47. Human Malaria Types [Lecture PPT]

PARA LEC | LE3 - 01 Malaria PAGE 17 of 22

 Figure 48. P. Falciparum blood stage parasite [Lecture PPT]

[Lecture PPT]
Figure 49. Summary of Malarial Life Cycle and Clinical Manifestations

PARA LEC | LE3 - 01 Malaria PAGE 18 of 22

Table 11. Formative Quiz
Note: Lecturer mentioned to answer FQ on Canvas, but there was no FQ published. FQ was lifted from 2025 Trans
# QUESTION
1. Where does sexual
multiplication of Malarial
parasites take place?
2. What is the most common
presentation of Plasmodium
falciparum malaria?
3. What is the vector of
Plasmodium malariae?
4. Plasmodium vivax infects
which of the following red
blood cell types?
5. Which one of the following
are NOT antimalarial
compounds?
PARA LEC | LE3 - 01 Malaria
CHOICES ANSWER KEY & RATIONALE
A. Mosquito gut 📋 The sexual cycle in the mosquito involves sporogony,
B. Mosquito spleen which leads to the formation of sporozoites.
→ In the gut of the mosquito, the male gametocytes
C. Human RBC A
exflagellate and produce eight sperm-like
D. Human liver microgametes which may fertilize the female
macrogamete to form a zygote.
A. Headache 📋 There are no absolute clinical features of malaria except for
B. Fever the regular paroxysms of fever with associated
asymptomatic intervals. The classical malaria paroxysms
C. Convulsion have three stages:
D. Jaundice → Cold stage - mild shivering quickly turning to violent
teeth chattering and shaking of the entire body due to
B intense peripheral vasoconstriction; lasts for 15 to 60
mins
→ Hot stage - temperature may reach a peak of 41°C or
more; lasts from 2 to 6 hours
→ Sweating stage - defervescence and diaphoresis or
profuse sweating; temperature lowers over the next 2 to
4 hours
A. Phlebotomus sandfly 📋 Vector for Leishmania spp.
B. Anopheles female mosquito 📋 Vector for Plasmodium spp.
C. Glossina tsetse fly
B
📋 Vector for Trypanosoma brucei
D. Reduviid triatomid bug 📋 Vector for Trypanosoma cruzi
A. RBCs of all ages 📋 Plasmodium vivax and Plasmodium ovale infect
📋 Plasmodium malariae infect mature or senescent RBCs
B. Reticulocytes reticulocytes or young RBCs
C. Mature RBCs
B
📋 Plasmodium falciparum and Plasmodium knowlesi
D. Senescent RBCs infect ALL stages of RBCs
A. Doxophylline 📋 For severe malaria, parenteral antimalarial treatment
B. Mefloquine should be started without delay after rapid clinical
assessment and confirmation of the diagnosis.
C. Quinine → The following antimalarial drugs are recommended:
D. Chloroquine A artesunate intravenous (IV) injection or intramuscular
(IM) injection, quinine IV or IM, or artemether IM.
E. Artemisinin
(Belizario p. 96)
→ Chloroquine was the mainstay of antimalarial treatment
for the last 50 years (Belizario p. 96)
PAGE 19 of 22
 📋SUMMARY TABLE [2025]

Table 12. Malarial Parasite

Plasmodium vivax
● Benign Tertian Malaria
● Erythrocytic Cycle: 48 Hours
Plasmodium ovale Plasmodium malariae Plasmodium falciparum Plasmodium knowlesi
● Quartan Malaria ● Malignant Tertian or Subtertian or ● Knowlesi Malaria
Aestivoautumnal Malaria ● Responds to Chloroquine and
● Associated with Burkitt’s lymphoma Primaquine
● Erythrocytic Cycle: 72 Hours ● Erythrocytic Cycle: 48 Hours ● Erythrocytic Cycle: Quotidian Patt

G ● Hypnozoite in the liver → relapse

E
● Infected RBC is enlarged ● Infected RBC is slightly ● Infected cells are normal to ● Infected RBC is the same size ● Infected RBC is 0.75x (smaller)
N
enlarged smaller in size
C ● Affinity for young RBCs or Reticulocytes ● Preference for old RBCs ● Infected RBCs of ALL stages ● Infect RBCs of ALL stages
H ● Absent in Black Africans since ● Found in Tropical Africa, ● Found in Subtropical and ● Found in the tropics, subtropics, and
A there is no reservoir host and West Africa, South America, Temperate areas sub-Saharan Africa
most Africans lack the duffy and Asia
antigen
● The predominant malarial ● Deadliest sp of Plasmodium ● Vector in RP is A. balabacensis &
species in most parts of the → 50% of all malaria cases A. maculatus
world

E
A
R
L
Y
/
R
I
N
G

F
O
R
M
● Signet or ring-shaped ● Single chromatin dot rings ● Single chromatin dot and a ● One of two chromatin dots ● Rings may show double
T ● Thick cytoplasm with a ● Exhibit fimbriation and cytoplasm ring; thicker than P. (Headphone Type) chromatin dots
R single, large chromatin dot Schüffner’s dots falciparum ● Found in the periphery of the RBC ● Appliqué forms may be seen as
O ● Cytoplasm: becomes → Infected RBC shows ● ‘Bird’s-eye’ forms may appear (accolé, appliqué) well as rectangular rings
P amoeboid and Schüffner’s granules like Schüffner’s ● Maurer’s clefts can be seen containing harboring one or more accessory
H dots may appear dots and take a violet older ring-form trophozoites chromatin dots
● Multiply-infected RBCs tinge ● Resemble the Schüffner’s dots but are ● Multiply-infected RBCs
● Multiply-infected RBCs usually larger and more coarse

PARA LEC | LE3 - 01 Malaria PAGE 20 of 22

 L
A
T
E

T
R
O
P
H
● Becomes amoeboid and ● Infected RBCs are often ● Compact ● Remain in ring form, but may become ● Band forms may appear that are
Schüffner’s dots are visible slightly enlarged ● May elongate across the host thicker and more compact similar in appearance to P.
with proper staining ● Exhibit fimbriation and RBC, forming a ‘band-form’ ● Amount of pigment and chromatin may malariae
→ Small-yellowish brown Schüffner’s dots ● May be oval with a vacuole also increase ● Stipplings appear called Sinton
pigment granules in forming a ‘basket-form’ and Mulligan’s stippling
cytoplasm ● Rounded chromatin
● Band-form appearance ● Ziemann’s stippling may be
→ Vivax band forms are present
larger than a normal RBC

S
C
H
I
Z
O
N
T
S

PARA LEC | LE3 - 01 Malaria PAGE 21 of 22

 ● 12-24 merozoites, each of ● 4-16, merozoites; ave: 8 ● 6-12 merozoites, often ● 8-24 merozoites ● 16 (average 10) merozoites
which contains a dot of (fewer merozoites) arranged in a rosette or ● Fills 2⁄3 of the infected RBC ● Sinton and Mulligan’s stippling
chromatin and a mass of ● Elongation to an oval shape irregular cluster ● Schizogony does NOT take place in the may be observed
cytoplasm and fimbriation are common peripheral blood but in capillaries of
● Schüffner’s dots organs and muscles
● The only stages seen in peripheral
blood are rings and gametocytes

G
A
M
E
T
O
C ● Cytoplasm is usually a darker ● Difficult to distinguish from P. ● Reduced size ● Crescent or sausage-shaped Shape and size:
Y blue and contains fine brown vivax ● Stains blue; abundant dark ● Pigment is more coarse and ● Macrogametocytes
T pigment throughout ● Slight enlargement of the pigment may be scattered concentrated in the macrogametocyte → spherical and fill the host
E → Schüffner’s dots may be infected RBC throughout the cytoplasm than the microgametocytes RBC
S seen with proper staining → The mature ● Pink to red ● Laveran’s bib: remnants of the host ● Microgametocyte
● Macrogametocytes are round macrogametocyte fills RBC → smaller than the
to oval and usually fill the host the host RBC macrogametocyte
cell → The microgametocyte Pigment:
● Microgametocytes are becomes smaller ● Macrogametocytes
usually the size of an ● Schüffner’s dots may be → Cytoplasm stains blue
uninfected RBC and have a seen with proper staining → Eccentric nucleus stains red
paler blue, pink or gray and fimbriation may occur ● Microgametocyte
cytoplasm ● Distinguished from P. → Cytoplasm usually stains
malariae by size of infected pale pink
cells and by Schüffner’s dots; → Nucleus stains darker red
less easy to differentiate from
P. vivax

PARA LEC | LE3 - 01 Malaria PAGE 22 of 22