○​ Associated with risk of

Plasmodium cardiac failure and adverse

perinatal outcomes.
Spp. ●​ Anemia from malaria is
exacerbated by helminth infections
●​ Malaria remains the leading in both children and pregnant
parasitic disease that causes women
mortality worldwide.
●​ 655,000 malaria-related deaths Millennium Development Goals (MDGs)
reported in 2010.
●​ 3.3 billion people are at risk for ●​ In 2000, the United Nations (UN)
infection. adopted the Millennium
●​ Identified by the World Health Declaration.
Organization (WHO) as one of the ●​ Blueprint for eradication of extreme
three major infectious disease poverty through eight quantifiable
threats along with: time-bound targets known as
○​ Human immunodeficiency Millennium Development Goals
virus/acquired immune (MDGs).
deficiency syndrome
(HIV/AIDS) MDG 6:
○​ Tuberculosis
●​ Reduce burden of HIV/AIDS,
○​ Together they cause more
malaria, and other diseases.
than 5 million deaths each
●​ Malaria component includes:
year.
○​ Reducing incidence and
mortality rates.
Impact
○​ Increasing
●​ Leads to decreased social and insecticide-treated bed net
economic productivity. coverage among children
●​ Contributes to a vicious cycle of below 5 years of age.
disease and poverty. ○​ Increasing anti-malarial
●​ Young children and pregnant coverage among children
women are the population groups below 5 years of age.
mostly affected.
Eight Millennium Development Goals
●​ Chronic malaria leads to anemia,
(2015):
associated with:
○​ Impaired physical and 1.​ Eradicate extreme poverty and
mental growth and hunger
development in children. 2.​ Achieve universal primary
○​ In pregnancy, anemia education
contributes to maternal 3.​ Promote gender equality and
morbidity and mortality.​ women empowerment
4.​ Reduce child mortality
5.​ Improve maternal health
 6.​ Combat HIV/AIDS, malaria, and ●​ Research Institute for Tropical
other diseases Medicine (RITM) reported nine
7.​ Ensure environmental cases of mixed malaria infection
sustainability (Plasmodium spp. positive for P.
8.​ Develop a global partnership for knowlesi).​
development

Causative Agent Life cycle of P. knowlesi:

●​ Disease is curable if promptly and ●​ Microscopically indistinguishable

adequately treated. from P. malariae.
●​ Parasites causing malaria belong to ●​ Differentiation achieved through
the genus Plasmodium. polymerase chain reaction (PCR)
●​ Transmitted by the bite of an assay and molecular
infected female Anopheles characterization.
mosquito.
●​ Medically important species to Morphology & Life Cycle
humans:
○​ Plasmodium falciparum ●​ Protozoans:
○​ Plasmodium vivax ○​ Pigment producers.
○​ Plasmodium ovale ○​ Ameboid in shape (some
○​ Plasmodium malariae more ameboid than others).
●​ Asexual cycle occurs in humans
P. falciparum and P. vivax (vertebrate, intermediate host).
●​ Sexual cycle occurs in Anopheles
●​ cause over 90% of all human mosquito (invertebrate, definitive
malaria cases. host)

Plasmodium knowlesi: Life Cycle Overview

●​ Described in humans in the ●​ Asexual cycle in humans:

Philippines and Southeast Asia. ○​ Schizogony → formation of
●​ Considered the fifth human malaria merozoites.
parasite. ○​ Gametogony → formation of
●​ Normally parasite of long-tailed gametocytes.
macaques (Macaca fascicularis). ●​ Sexual cycle in mosquito:
●​ Humans working in forest fringe ○​ Sporogony → formation of
→ great risk for infection. sporozoites.
●​ First naturally acquired human ●​ All human species of malaria have
infection: 1965, Sarawak, similar life cycles.
Malaysia.
●​ Other foci of infection: Thailand and
China (2008).
●​ Philippines first case: 2006.
Infection in Humans ●​ Erythrocytes rupture →
merozoites released into blood →
●​ Female Anopheles mosquito bites invade new red cells.
and sucks blood. ●​ Asexual cycle is synchronous,
●​ Salivary fluids containing periodic, and species-determined
sporozoites are injected.
●​ Sporozoites (infective stage): Sexual Cycle in Mosquito
○​ Immediately carried to the
liver. ●​ Some merozoites → develop into
○​ Enter parenchymal cells. gametocytes:
○​ Undergo exo-erythrocytic ○​ Microgametocytes (male).
schizogony → produce ○​ Macrogametocytes
merozoites. (female).
○​ Number and duration of ●​ Female mosquitoes ingest
merozoite production = gametocytes during blood meal.
species-dependent. ●​ In mosquito gut:
●​ Merozoites → enter erythrocytes ○​ Male gametocytes
(red blood cells). exflagellate → produce 8
●​ P. vivax and P. ovale: sperm-like microgametes.
○​ Some merozoites re-invade ○​ Microgametes fertilize
liver cells → form female macrogamete →
hypnozoites (dormant form zygote.
forms). ○​ Zygote becomes motile
○​ Remain quiet for years. ookinete → penetrates gut
wall.
Development in Red Blood Cells ○​ Ookinete develops into
oocyst.
●​ Merozoite grows into ring form → ○​ Oocyst grows → produces
develops into trophozoite. sporozoites.
●​ Trophozoite: ○​ Sporozoites enter
○​ Extended cytoplasm. mosquito salivary glands.
○​ Large chromatin mass → ○​ Sporozoites injected into
divides → produces more another human during the
merozoites within next blood meal.
schizonts. ●​ Cycle in mosquito: 8–35 days
●​ P. falciparum merozoites: (temperature-dependent).
○​ Develop in parasitophorous
vacuolar membrane (PVM). Morphology
○​ Modify structural and
antigenic properties of red ●​ Early trophozoite form:
cells. ○​ Ring-shaped.
●​ Parasites feed on hemoglobin → ○​ Red chromatin dot.​
produce pigment (hematin).​
 ○​ Scant blue cytoplasm ●​ Small threadlike blue cytoplasmic
(when stained with Giemsa circle
or Wright’s stain). ●​ One or two small red chromatin
●​ Trophozoite: dots
○​ Large chromatin mass. ●​ Double chromatin common
○​ Prominent ameboid ●​ Marginal forms common
cytoplasm spread in
erythrocyte. Growing trophozoite:
●​ Schizont:
○​ Chromatin divides into 2 or ●​ Remains in ring form
more masses. ●​ Grows resembling small
○​ Surrounded by merozoites. trophozoite of P. vivax
○​ Number of merozoites = ●​ Usually oldest asexual stage seen
species-dependent. in peripheral blood
○​ Clumps of pigment
Large trophozoite:
accumulate in mature
schizont. ●​ Seldom present
●​ Gametocyte stage:
○​ Fills the entire red blood Schizont (presegmenting):
cell.
○​ Large chromatin mass. ●​ Not present
○​ Blue cytoplasm with
pigment. Schizont (mature):
○​ Shape: round to
●​ Rarely present
banana-shaped.
●​ 8–24 merozoites
○​ Microgametocyte: lighter
●​ Smaller than other species
blue cytoplasm.
○​ Macrogametocyte: darker
Gametocyte:
blue cytoplasm.
●​ Species identification → based on ●​ Present in peripheral blood
morphological characteristics of stream
developmental stages ●​ similar to P. vivax
●​ crescent or sausage shape
Plasmodium falciparum (Malignant
tertian) Stages in peripheral blood:

Infected RBC: ●​ Ring forms

●​ Gametocytes
●​ Normal size ●​ Other stages rare
●​ Multiple infection very common
Length of asexual cycle:
Small trophozoite:
●​ 48 hours or less
●​ Similar to P. vivax​
Plasmodium vivax (Benign tertian) ○​ Parasite almost fills enlarged
cells
Infected RBC:
Gametocyte:
●​ Larger than normal, pale, often
bizarre ●​ Microgametocyte
●​ Schüffner’s dots often present ○​ Light red to pink chromatin
●​ Multiple infection not uncommon ○​ Diffuse, central
○​ Tint to light blue cytoplasm
Small trophozoite: ○​ Yellowish brown pigment
throughout cytoplasm
●​ Signet-ring form ○​ Round, size of normal RBC
●​ Heavy red dot with blue ●​ Macrogametocyte
cytoplasmic ring ○​ Small, compact
○​ Dark red eccentric
Growing trophozoite:
chromatin
●​ Similar to small trophozoite but with: ○​ Dark blue cytoplasm, no
○​ Increased cytoplasm vacuoles
○​ Ameboid activity ○​ Dark brown pigment
○​ Small yellowish-brown scattered
pigment granules that
Stages in peripheral blood:
increase with parasite age
●​ All stages present
Large trophozoite:
Length of asexual cycle:
○​ Large chromatin mass
○​ Loose, irregular, or ●​ 48 hours
compact cytoplasm
○​ Fine brown pigment Plasmodium ovale (Benign tertian)
increases with age
○​ Parasite fills cell in 30–40 Infected RBC:
hours
○​ Somewhat larger than
Schizont (presegmenting): normal
○​ Fringed or irregular edge,
○​ Chromatin divided oval in shape
○​ Cytoplasm separates into ○​ Schüffner’s dots appear
strands/particles even in younger stages​
○​ Pigment collects in parts of
parasite ●​ Stains more readily and deeply
than P. vivax
Schizont (mature):
Small trophozoite:
○​ 12–24 merozoites
○​ Pigment in 1–2 clumps ●​ Small, darker in color
 ●​ More solid than P. falciparum Plasmodium malariae (Quartan)
●​ Schüffner’s dots present in
almost 100% of infected cells Infected RBC:

Growing trophozoite: ●​ Larger than normal, pale, often

bizarre
●​ Resembles P. malariae but: ●​ Schüffner’s dots often present
○​ Considerably larger ●​ Multiple infection not uncommon
○​ Pigment lighter and less
conspicuous Small trophozoite:

Large trophozoite: ●​ Similar to P. vivax but with:

○​ Blue cytoplasmic circle
●​ Seldom present ○​ Smaller, thicker, and
heavier
Schizont (presegmenting):
Growing trophozoite:
●​ 25% of infected cells are
oval-shaped ●​ Chromatin rounded or elongated
●​ Round parasite in center of oval ●​ Cytoplasm compact or in narrow
cell band across cell
●​ Many cells with indefinite fringed ●​ Dark brown granules may have
outline peripheral arrangement
●​ Pigment lighter and less coarse
than P. malariae Large trophozoite:

Schizont (mature): ●​ Chromatin elongate, indefinite

outline
○​ Usually 8 merozoites ●​ Dense, compact cytoplasm
○​ Arranged around a central (rounded, oblong, or band forms)
block of pigment ●​ Pigment granules larger and
darker than P. vivax
Gametocyte: ●​ Parasite frequently fills cells

●​ Distinguished from P. malariae by Schizont (presegmenting):

size of infected cells
●​ Presence of Schüffner’s dots ●​ Similar to P. vivax but with:
●​ Difficult to differentiate from P. vivax ○​ Smaller parasite
○​ Less chromatin division
Stages in peripheral blood: ○​ Delayed clumping of
pigment
●​ All stages present
Schizont (mature):
Length of asexual cycle:
○​ 6–12 merozoites (average
●​ 48 hours 8–10)
 ○​ Arranged in rosette form
○​ Parasite almost fills cell
Clinical Features
Gametocyte:
●​ No absolute signs → only regular
●​ Same as P. vivax paroxysms of fever with
●​ Smaller asymptomatic intervals.
●​ Fills or almost fills cells ●​ Prodromal symptoms:
○​ Weakness, exhaustion
Stages in peripheral blood: ○​ Desire to stretch & yawn
○​ Aching bones, limbs, back
●​ All stages present
○​ Loss of appetite
Length of asexual cycle: ○​ Nausea & vomiting
○​ Chilling sensation
●​ 72 hours ●​ Early onset symptoms:
○​ Malaise
○​ Backache
Pathogenesis and Clinical
○​ Diarrhea
Manifestations
○​ Epigastric discomfort
Pre-patent period (sporozoite injection →
parasites detectable in blood): Classical Malaria Paroxysms (3 Stages)

●​ P. falciparum: 11–14 days 1.​ Cold Stage (15–60 mins)

●​ P. vivax: 11–15 days ○​ Sudden feeling of coldness
●​ P. ovale: 14–26 days & apprehension
●​ P. malariae: 3–4 weeks ○​ Mild shivering → violent
teeth chattering & body
Incubation period (sporozoite injection → shaking
clinical symptoms): ○​ High/rising core
temperature but intense
●​ P. falciparum: 8–15 days vasoconstriction
●​ P. vivax: 12–20 days ○​ Vomiting may occur
●​ P. ovale: 11–16 days ○​ Febrile convulsions
●​ P. malariae: 18–40 days possible in children
●​ Overall range: 9 days to 3 years 2.​ Hot Stage (2–6 hrs)
(depends on strain, sporozoite dose, ○​ Patient becomes hot,
immune status, chemoprophylaxis) flushed
○​ Symptoms: headache,
Risk duration: palpitations, tachypnea,
epigastric discomfort,
●​ Any person who has traveled to
thirst, nausea, vomiting
malaria-endemic areas remains at
○​ Temperature up to 41°C+
risk for up to 2 years or longer after
○​ May develop confusion or
leaving
delirium
○​ Skin flushed & hot
 ●​ Medication history:
chemoprophylaxis or chemotherapy
3.​ Sweating Stage (2–4 hrs) used before infection
○​ Profuse sweating ●​ Geographical origin of infection
(diaphoresis) also influences disease distribution
○​ Temperature lowers
○​ Symptoms diminish Recrudescence vs Relapse
○​ Total attack duration: 8–12
hours ●​ Recrudescence → renewal of
parasitemia/clinical symptoms from
Periodicity of Attacks persistent asexual parasitemia (no
exo-erythrocytic cycle)
●​ P. falciparum: 48 hrs (paroxysms ●​ Relapse → renewed parasitemia
every 2nd day) after blood is parasite-free, due to
●​ P. vivax: 48 hrs (alternate days) reactivation of hypnozoites in the
●​ P. ovale: 48 hrs (alternate days) liver
●​ P. malariae: 72 hrs (paroxysms on ○​ Occurs in P. vivax and P.
days 1 & 4) → “quartan malaria” ovale
●​ P. knowlesi: Quotidian (daily) ○​ Triggers: cold, fatigue,
fever, non-relapsing (no trauma, pregnancy,
exoerythrocytic stage infections (including
falciparum malaria)
Differences in Erythrocyte Infection
Pathological Processes in Malaria
●​ P. vivax and P. ovale → infect only
young red blood cells ●​ Caused by the erythrocytic cycle
●​ P. malariae → infects only aging ●​ P. falciparum merozoite invasion
red blood cells → reduces RBC deformability (due
●​ P. falciparum and P. knowlesi → to cytoskeleton changes, increased
infect erythrocytes of all ages stiffness & viscosity)
●​ This difference limits parasitemia in ●​ Invasion produces electron-dense
non-falciparum species (<3%), submembranous structures →
while P. falciparum can reach much enlarge to form “knobs”
higher levels → leads to greater
severity and mortality Knobs & Cytoadhesion

Factors Affecting Course and Severity ●​ Knobs contain proteins:

○​ Rosettins
●​ Parasite factors: species and strain ○​ Riffins
●​ Host factors: ○​ Histidine-rich proteins
○​ Age (HRP)
○​ Genetic constitution ○​ PfEMP-1 (Plasmodium
○​ Immunity falciparum erythrocyte
○​ General health membrane protein 1) →
○​ Nutritional status most adhesive protein
 ●​ PfEMP-1: Cytokine Effects & Acute Symptoms
○​ Encoded by var gene family
○​ Clonally variant → allows ●​ Cytokine release at schizont
immune evasion rupture → causes:
○​ Main ligand for ○​ Fever & febrile paroxysms
cytoadherence (binds to ○​ Headache
parasitized and ○​ General body aches &
non-parasitized RBCs & prostration
platelets) ●​ Host immune response + altered
●​ Rosettins + PfEMP-1 → form RBC surface membranes → leads
rosettes to:
●​ HRP → strengthens adhesion by ○​ Altered regional blood flow
localizing to cytoadherence ligands (vascular endothelium)
●​ Febrile temperature enhances ○​ Biochemical changes
PfEMP-1–mediated cytoadherence ○​ Anemia
even in ring stages ○​ Tissue & organ hypoxia
○​ Increased capillary
Altered Erythrocytes & Antigenic permeability → fluid leakage
Changes ○​ Vascular congestion →
tissue infarction & necrosis
●​ Infected erythrocytes undergo
altered membrane transport Severe Malaria – Neurological
mechanisms Manifestations
●​ Hemoglobin digestion → forms
pigment hematin ●​ Impairment of consciousness
●​ Strain-specific neoantigens ●​ Delirium & generalized
expressed on RBC membrane convulsions
●​ Soluble antigens of P. falciparum ●​ Severe hemolytic anemia:
→ induce pro-inflammatory & ○​ Hematocrit <20%
anti-inflammatory cytokines (from ○​ Hemoglobin <7 g/dL
monocytes & macrophages) ○​ Hyperbilirubinemia >50
●​ Glycosylphosphatidyl inositol mmol/L
(GPI) moieties: ●​ Cerebral malaria:
○​ Covalently linked to surface ○​ Diffuse symmetric
antigens encephalopathy
○​ Act like lipopolysaccharide ○​ Retinal hemorrhage
(LPS) of gram-negative ○​ Bruxism (fixed jaw closure,
bacteria teeth grinding)
○​ Stimulate monocytes → ○​ Mild neck stiffness
release TNF/cachexin → ○​ Pouting reflex (elicited by
causes malarial fever stroking sides of mouth)
●​ Lumbar tap findings:
○​ Normal–elevated opening
pressure
○​ Clear CSF
 ○​ <10 leukocytes/mL ○​ Definition:
○​ Slightly elevated protein & ■​ Serum creatinine
CSF lactic acid >265 mmol/L (3
●​ If untreated → progresses to mg/dL)
persistent coma & death ■​ 24-hour urine output
●​ Reversibility: With prompt <1 mL/kg/hr despite
treatment → neurological rehydration
complications are reversible, ■​ Asexual forms of
majority fully recover parasite present in
peripheral blood
Severe Malaria – Respiratory smear
Manifestations ○​ Early findings:
Hyperkalemia &
●​ Altered pulmonary function Hyperuricemia
common: ●​ Pathogenesis of
○​ Airflow obstruction Malaria-Associated ARF
○​ Impaired ventilation & gas ○​ Cytoadherence, rosette
transfer formation, sequestration of
○​ ↑ Pulmonary phagocytic parasitized RBCs → ↓ tissue
activity perfusion → ↓ renal blood
●​ African children (postmortem flow
findings): ○​ TNF increase in tubular
○​ Pneumonitis from epithelial cells →
sequestered parasitized inflammatory infiltration +
RBCs + inflammatory cells altered tubular transport →
●​ Adults: tubular damage &
○​ Non-cardiogenic dysfunction
pulmonary edema ○​ GPI & falciparum antigens
○​ Acute Respiratory Distress → cytokine release → ↓
Syndrome (ARDS) systemic vascular
●​ High mortality (>80%) with resistance + ↑ renal
pulmonary edema vascular resistance
●​ Predisposing factors for ○​ Final result: Acute tubular
pulmonary edema: necrosis → Acute renal
○​ Hyperparasitemia failure
○​ Renal failure
○​ Pregnancy Malaria in Pregnancy

Severe Malaria – Renal Manifestations ●​ Increased maternal risks:

○​ Maternal death
●​ Acute Renal Failure (ARF) ○​ Maternal anemia
○​ Incidence: up to 60% of ●​ Adverse fetal outcomes:
patients with severe ○​ Intrauterine growth
falciparum malaria retardation (IUGR)
○​ More common in males
 ○​ Spontaneous abortion ○​ Hemiparesis
○​ Stillbirth ○​ Cerebellar ataxia
○​ Low birth weight → higher ○​ Speech disorders
neonatal death risk ○​ Generalized spasticity
●​ Non-immune pregnant women → ○​ Behavioral disturbance
especially susceptible to severe
malaria complications: Immunity & Resistance
○​ Cerebral malaria
○​ Hypoglycemia ●​ Not all infected individuals
○​ Pulmonary edema develop severe illness or die
●​ Stable endemic areas: repeated
Malaria in Pregnancy (Partially Immune exposure → specific immunity
Women) ○​ Protects against severe
complications in young
●​ Partially immune pregnant women children
(esp. primigravid) ○​ Older patients → only mild
○​ Severe anemia may develop febrile illness
○​ Other severe malaria ●​ First-time exposure → outcomes
complications unlikely vary:
●​ Falciparum malaria effects: ○​ From apparent resistance
○​ Can induce uterine → death
contractions → premature ●​ Resistance:
labor ○​ Nonspecific
○​ In severe malaria, fetal ○​ May be acquired or innate
prognosis is poor ○​ Does not necessarily
depend on prior exposure
Malaria in Children
Poor Prognostic Factors in Falciparum
●​ Medical emergency → can be Malaria
rapidly fatal
●​ Initial symptoms may be atypical ●​ Parasitological indicators:
& difficult to recognize ○​ Hyperparasitemia =
●​ Within hours → life-threatening >250,000/µL OR >5% RBCs
complications infected
●​ Most common complications: ○​ Presence of schizonts
○​ Cerebral malaria (mature/immature) in
○​ Severe anemia peripheral smear
○​ Respiratory distress ○​ ≥10% RBCs infected →
○​ Hypoglycemia 50% mortality rate, esp. in
●​ Seizures common (before or after non-immune cases despite
coma) → strongly linked to treatment
neurologic sequelae ●​ Clinical indicators:
●​ Opisthotonos may occur ○​ Deep coma
●​ Sequelae (10% of survivors of ○​ Absence of corneal light
cerebral malaria): reflex
 ○​ Respiratory distress ●​ Specimens: may be taken any time;
(acidosis) all blood stages of the parasite may
○​ Circulatory collapse be found.
○​ Decerebrate or decorticate ●​ Falciparum malaria: usually only
rigidity ring forms are found; gametocytes
○​ Opisthotonos appear about 10 days after
○​ Age <3 years symptoms begin.
●​ Laboratory indicators: ●​ Blood smears frequency:
○​ Blood glucose <2.2 mmol/L ○​ Obtaining smears every 6–8
○​ Venous lactic acid >5 hours is usually appropriate.
mmol/L ○​ Continue until malaria is
○​ Serum enzymes diagnosed or confidently
(aminotransferases) → ruled out.
>3-fold increase ○​ Repeated testing may be
○​ Hemoglobin <5 g/dL needed for several days.
○​ Blood urea >60 mg/dL ●​ Monitoring after diagnosis:
○​ Serum creatinine >265 ○​ Smears still needed to
mmol/L monitor treatment
○​ PMNs with visible malaria response.
pigment >5% ○​ Non-seriously ill patients:
○​ Low antithrombin III monitor once daily.
○​ Very high plasma TNF ○​ Seriously ill patients:
monitor 2–3 times daily until
Diagnosis of Malaria significant improvement.
○​ Monitoring continues until
●​ Prompt and adequate diagnosis is parasitemia is cleared.
necessary to manage malaria
effectively and prevent Rapid Diagnostic Tests (RDTs)
life-threatening complications.
●​ Classic paroxysms of fever may ●​ Introduced due to limitations in
occur, but initial symptoms are microscopy (technical & personnel
non-specific → not reliable for constraints).
diagnosis. ●​ Use immunochromatographic
●​ Treatment based on clinical methods to detect
findings alone often results in Plasmodium-specific antigens in
unnecessary and irrational drug finger prick blood.
use. ●​ Target antigens:
○​ Histidine-rich protein II
Microscopic Diagnosis (Gold Standard) (HRP II): produced by
trophozoites & young
●​ Microscopic identification of gametocytes of P.
parasites in thick and thin blood falciparum.
smears stained with Giemsa or ○​ Plasmodium lactate
Wright’s stain remains the gold dehydrogenase (pLDH):
standard. produced by both sexual &
 asexual stages; distinguishes Serologic Diagnosis
P. falciparum vs. non-P.
falciparum, but not among ●​ Available methods (e.g., IHA, IFAT,
non-falciparum species. ELISA) cannot make a definitive
○​ Plasmodium aldolase: diagnosis of acute malaria.
glycolytic enzyme, present in ●​ Cannot distinguish between
all species (panmalarial current and past infection.
antigen, PMA). ●​ More useful in epidemiologic
●​ Performance: studies.
○​ Done in 15–30 minutes; no
electricity/equipment needed. Molecular Diagnosis
○​ Most kits: >90% specificity.
●​ PCR enhances microscopic
○​ HRP II kits: sensitivity
diagnosis:
92.5%, specificity 98.3%.
○​ Useful for low parasitemia.
○​ pLDH kits: sensitivity 88.5%,
○​ Helps detect mixed
specificity 99.4%.
infections
●​ Advantages: simple, quick, usable
by village health workers.
Treatment of Malaria
●​ Disadvantages:
○​ Lower sensitivity at low ●​ Antimalarial drugs act on different
parasitemia. phases of the parasite life cycle.
○​ Cannot quantify parasite ●​ Drug classifications:
density. ○​ Causal prophylactic drugs
○​ Cannot distinguish P. vivax, – prevent parasite
P. ovale, P. malariae. establishment in the liver.
○​ Cannot differentiate sexual ○​ Blood schizonticidal drugs
vs. asexual stages. – attack parasite in red
○​ May stay positive after blood cells, preventing or
parasite clearance. terminating clinical attacks.
○​ Higher cost than ○​ Tissue schizonticides – act
microscopy. on pre-erythrocytic forms
●​ Philippines studies: in the liver.
○​ Sensitivity & specificity ○​ Gametocytocidal drugs –
below WHO ideal (95% / destroy sexual forms of the
90%). parasite in the blood.
○​ Causes: manufacturer ○​ Hypnozoitocidal
issues, instability to (antirelapse) drugs – kill
temperature/humidity, user dormant liver forms.
errors. ○​ Sporonticidal drugs –
○​ Quality assurance is inhibit oocyst development
necessary before large-scale in the mosquito gut,
deployment. preventing transmission.​

●​ Main uses of antimalarial drugs:

 ○​ Protective (prophylactic): ○​ Recommends
■​ Used before artemisinin-based
infection occurs or combination therapies
before it becomes (ACTs).
evident. ○​ Replaces chloroquine +
■​ Prevents infection or sulfadoxine-pyrimethamine
its symptoms. ○​ Recommended drug
■​ Example: a blood combinations:
schizonticidal drug ■​ Artemether +
present in the blood lumefantrine
when merozoites ■​ Artesunate +
leave the liver can amodiaquine
prevent symptomatic ■​ Artesunate +
malaria. mefloquine
○​ Curative (therapeutic): ■​ Artesunate +
■​ Action on sulfadoxine-pyrimet
established hamine
infection. ●​ Severe malaria treatment:
■​ Involves blood ○​ Start parenteral treatment
schizonticidal drugs immediately after rapid
for acute attack. clinical assessment and
■​ Includes radical confirmed diagnosis.
treatment for ○​ Recommended drugs:
relapsing malaria ■​ Artesunate IV/IM
(dormant liver forms). ■​ Quinine IV/IM
○​ Preventive (transmission ■​ Artemether IM
blocking): ○​ Special case:
■​ Prevents mosquito ■​ If oral, IM, or IV
infection using treatments
gametocytocidal unavailable → a
drugs. single artesunate
■​ Interrupts suppository at
sporogonic phase in referral reduced risk
the mosquito gut. of death or
●​ Chloroquine permanent disability
○​ Former mainstay of (based on
treatment for 50 years. placebo-controlled
○​ Now ineffective against trial)
multidrug-resistant (MDR)
falciparum malaria.

Current DOH Malaria Control Additional Antimalarial Treatment Notes

Program (MCP):
●​ Gametocytocidal drugs ■​ Risk of relapse
○​ Reduce transmission. decreases with
○​ Primaquine: higher primaquine
■​ 0.75 mg base/kg dose (mg/kg).
body weight, single ■​ Repeated relapses =
oral dose. debilitating at any
■​ Provides added age → prevention is
benefit to essential.
artemisinins in ●​ Plasmodium malariae &
eliminating Plasmodium ovale
gametocytes. ○​ Still sensitive to
■​ Recommended as an chloroquine.
addition to ACTs. ○​ P. ovale treatment (for
■​ Contraindications: relapsing fever): same as P.
■​ Risk of vivax → chloroquine +
hemolysis in primaquine.
G6PD-deficie ○​ Mixed infections:
nt patients. ■​ ACTs remain
■​ Pregnancy. mainstay treatment.
■​ Children < 4 ■​ Artemisinin-based
years old. compound + long
●​ Plasmodium vivax malaria half-life partner drug
○​ Remains generally sensitive effective:
to chloroquine, but ■​ Artesunate +
resistance increasing (esp. amodiaquine.
Indonesia, Peru, Oceania). ■​ Dihydroartem
○​ Sensitive to other isinin +
antimalarial drugs, but less piperaquine.
sensitive to artesunate + ■​ Radical treatment
sulfadoxine-pyrimethamine with primaquine for
○​ Primaquine: confirmed P. vivax
■​ Effective against and P. ovale
asexual stages and infections.
liver stages. ●​ Artemisinin and derivatives
■​ Combination: (Qinghaosu derivatives):
Chloroquine (blood ○​ Artesunate, Artemether.
stage) + Primaquine ○​ Produce rapid clearance of
(liver stage) → parasitemia and rapid
radical treatment. symptom resolution.​
■​ Prevents relapse.
■​ 14-day course of ○​ Elimination: rapidly cleared
primaquine required from the body.
for radical cure. ○​ Treatment duration
depends on partner drug:
 ■​ Partnered with ●​ Contraindications & Special
short-acting drugs Cases
(tetracyclines, ○​ Tetracycline: contraindicated
clindamycin) → 7-day in
course. ■​ Pregnant women.
■​ Partnered with ■​ Children < 8 years
long-acting drugs old (risk of
(mefloquine, congenital defects).
amodiaquine) → ○​ Preferred in pregnancy:
3-day course. ■​ Quinine +
○​ Additional advantage: clindamycin, 7-day
reduce gametocyte carriage course.
→ lowers transmission. ●​ Drug Resistance
○​ Especially useful in ●​ Involves mainly chloroquine
low-to-moderate +sulfadoxine-pyrimethamine.
endemicity areas ●​ Certain strains of P. falciparum
are MDR (multidrug resistant).
Quinine and Drug Resistance in Malaria ○​ Parasite clearance:
■​ Normally cleared from
●​ Quinine sulfate + doxycycline / blood within 3 days
clindamycin after start of
○​ Second-line drug when: treatment.
■​ Artemisinins ■​ Definitely cleared in
unavailable (e.g., IV 6–7 days.
artesunate). ●​ Resistance Grading (Asexual
■​ Failure to respond Parasitemia Patterns)
to artemisinin therapy. ○​ RI (mildest form):
○​ Tetracyclines and ■​ Initial clearance, but
clindamycin: effective but recrudescence
slow-acting antimalarials. within 1 month.
●​ Disadvantages of Quinine ■​ Early RI: clearance in
○​ Toxic side effects: first 48 hours,
○​ Cardiotoxicity. recrudescence within
○​ Cinchonism → tinnitus, 14 days.
headache, blurring of ■​ Late RI: clearance in
vision. first 48 hours,
○​ Rapid administration is recrudescence day
unsafe. 14–28
○​ Must be given as slow
rate-controlled infusion. Drug Resistance & Treatment
○​ Requires ECG monitoring + Classification in Malaria
frequent vital signs check.​
●​ Resistance Grading​
 ○​ RII resistance: ○​ Late Clinical Failure (LCF):
■​ Initial reduction in ■​ Intense
parasitemia after transmission areas:
treatment. ■​ (a) Danger
■​ Failure to clear signs/severe
asexual parasites. malaria after
■​ Parasitemia Day 3 with
increases again parasitemia
soon after. (not ETF).
○​ RIII resistance (severest ■​ (b)
form): Parasitemia +
■​ No significant axillary temp
change in ≥ 37.5°C, Day
parasitemia with 4–14 (not
treatment. ETF).
■​ Or parasitemia will ■​ Low–moderate
eventually increase. transmission areas:
●​ Multidrug-resistant (MDR) malaria ■​ (a) Danger
○​ Defined as treatment failure signs/severe
with ≥3 antimalarial agents. malaria after
○​ Combination of artesunate Day 3 with
+ mefloquine: now first-line parasitemia
regimen in some Southeast (not ETF).
Asian countries. ■​ (b)
Parasitemia +
Classification of Response to Malaria axillary temp
Treatment ≥ 37.5°C (or
fever
●​ Early Treatment Failure (ETF) history), Day
(applies to both intense and 4–28 (not
low–moderate transmission areas): ETF).
○​ (a) Development of danger ○​ Late Parasitological Failure
signs/severe malaria on (LPF):
Day 1–3 with parasitemia. ■​ Intense
○​ (b) Parasitemia on Day 2 transmission areas:
higher than Day 0, ■​ Parasitemia
regardless of temperature. on Day 14 +
○​ (c) Parasitemia on Day 3 axillary temp
with axillary temp ≥ 37.5°C. ≥ 37.5°C, not
○​ (d) Parasitemia on Day 3 = meeting ETF
25% of Day 0 count.​ or LCF.
■​ Low–moderate
●​ Late Treatment Failure (LTF) → transmission areas:
subdivided:
 ■​ Parasitemia ●​ Not recommended in cerebral
Day 7–28 + malaria:​
axillary temp
≥ 37.5°C, not ○​ Corticosteroids.​
meeting ETF
or LCF.​ ○​ Other anti-inflammatory
agents.​
●​ Adequate Clinical &
Parasitological Response (ACPR): ○​ Low molecular weight
○​ Intense transmission dextran.​
areas: No parasitemia by
Day 14, regardless of temp, ○​ Epinephrine.​
without ETF/LTF.
○​ Low–moderate ○​ Heparin.
transmission areas: No
parasitemia by Day 28, Proper Management of Malaria
regardless of temp, without
ETF/LTF. ●​ Proper management includes
general and supportive measures,
Management of Complications in Severe especially in P. falciparum
Malaria infections.​

●​ Renal failure: ●​ Fluid replacement or blood

○​ Dopamine: 3–5 μg/kg/min. transfusion must be administered
○​ If no response despite with care to avoid pulmonary
rehydration & management, edema.​
and blood urea/creatinine
rising → dialysis indicated. ●​ Antipyretics and sponging for high
●​ Seizure control: fever are important, especially in
○​ Diazepam: children, to prevent convulsions.​
■​ Adults: 10 mg IV.
■​ Pediatrics: 0.3 mg/kg ●​ Blood sugar monitoring is
IV, up to 10 mg. essential, especially in severe
○​ Status epilepticus → malaria.​
Phenytoin:
■​ Loading dose: 13–18 ●​ If hypoglycemia develops:​
mg/kg (peds: 15–20
mg/kg slow IV). ○​ Give 50 mL of 50%
■​ Maintenance dose: dextrose (1.0 mL/kg for
3–5 mg/kg/day children), diluted in equal
(peds: 5 mg/kg/day, volume of infusion fluid.​
divided into 2 doses).​
○​ Infuse over 5 minutes,
followed by continuous IV
 infusion of 5–10% ○​ 2.1 billion at low risk (<1
dextrose. case/1,000 population) →
94% live outside WHO
Epidemiology of Malaria African Region.
○​ 1.2 billion at high risk (>1
●​ Malaria is the world’s most case/1,000 population):
important tropical parasitic ■​ 47% in WHO African
disease. Region
●​ It kills more people than any other ■​ 37% in Southeast
communicable disease except Asian Region
tuberculosis. ●​ 2010 WHO Report:
●​ In many developing countries, ○​ Estimated 216 million cases
especially in Africa, malaria causes: of malaria.
○​ High mortality ○​ 81% (171 million) in African
○​ Increased medical costs Region.
○​ Loss of labor days ○​ 13% in Southeast Asian
●​ Geographical areas affected by Region.
malaria have shrunk over the past ○​ 655,000 deaths reported.
50 years, but control is becoming ○​ 91% of deaths in Africa.
harder. ○​ 86% of deaths were
●​ Spread of malaria linked to: children under 5 years.
○​ Road building
○​ Mining Trends
○​ Logging
○​ New agricultural and ●​ 2000–2010: global malaria incidence
irrigation projects decreased by 17%.
(especially in “frontier” areas ●​ Mortality decreased by 25% during
like forest fringes, mountain the same period.
valleys, reclaimed areas) ●​ Regional reductions:
●​ Other factors worsening malaria ○​ European Region → 99.5%
situation: reduction
○​ Disintegration of health ○​ American Region → 60%
services reduction
○​ Armed conflict ○​ Western Pacific Region →
○​ Mass movements of 86% reduction
refugees
Western Pacific Region
Global Burden
●​ World Malaria Report 2011:
●​ Malaria remains a public health ○​ >50% decrease in cases in:
problem in 90+ countries, affecting China, Philippines,
3.3 billion people. Republic of Korea,
●​ At risk population:​ Solomon Islands, Vietnam.​
 ○​ 25–50% decrease in cases ●​ The mortality rate for malaria
in: Lao PDR, Malaysia, decreased by 88.2% from 2005 to
Vanuatu. 2009.
○​ No notable change in: ●​ Morbidity rate decreased by 58.3%,
Cambodia, Papua New with 18,781 malaria cases reported
Guinea. in 2009.
●​ Blood smear results (2005–2009):
Philippines ○​ 69.4–80% → P. falciparum
○​ 17.0–23.4% → P. vivax
●​ Malaria has not been among the 10 ○​ ~1% → P. malariae
leading causes of morbidity since ○​ 0.5% → mixed infection
2006. (usually falciparum + vivax)
●​ Cases decreasing (notable in
2009). Macrostratification of malaria endemic
●​ High prevalence areas (2010 areas
DOH-MCP report):
○​ Regions IV-B, Caraga, III, ●​ Purpose: classify provinces based
XII, II​ on annual incidence, helps in
planning, policy-making, resource
●​ At-risk population: ~10.8 million allocation for Malaria Control
people, mostly: Program (MCP).
○​ Farmers ●​ Category A: ≥1000 cases
○​ Indigenous cultural groups ●​ Category B: 100–<1000 cases
○​ Miners ●​ Category C: <100 cases
○​ Forest product gatherers ●​ Category D: No documented
○​ Soldiers indigenous case in past 5 years
●​ 59 out of 80 provinces endemic for
malaria: Trends (2000–2009):
○​ 60.4% in Luzon
○​ 39.5% in Mindanao ●​ Category A: reduced from 26 (2000)
○​ 0.1% in Visayas → 9 (2005) → 5 (2008)
●​ Top 5 provinces with highest ●​ Category B: 22 (2000) → 31 (2005)
malaria cases (2009): → 27 (2008)
○​ Cagayan ●​ Malaria-free provinces: 13 (2000)
○​ Isabela → 22 (2009)
○​ Palawan ●​ From 2005 to 2009:
○​ Sulu ○​ 4 provinces (A), 8
○​ Tawi-Tawi provinces (B), 8 provinces
●​ In areas of low malaria endemicity, (C) → reclassified to lower
there is a clustering of cases, categories
resulting in pockets of high ○​ Nueva Ecija → shifted to
endemicity.​ higher category
Transmission ●​ Purpose: evaluate amount &
conditions of transmission in a
●​ Peak transmission: beginning & locality → basis for control efforts.
end of rainy season. ●​ Includes:
●​ Principal malaria vector ○​ Epidemiologic data
(Philippines): Anopheles minimus (mortality & morbidity)
var. flavirostris ○​ Human host investigations:
○​ Night biter, breeds in blood exam, spleen exam
slow-flowing, shaded ○​ Vector investigations:
streams in foothills identification of mosquito
○​ Can adapt to irrigation species, breeding sites,
ditches, rice fields, pools, mosquito density
wells
○​ Mildly exophagic (feeds Prevention and Control of Malaria
outdoors) & zoophilic (feeds
on animals) in Palawan ●​ Early diagnosis and prompt
○​ Flight range: ~1–2 km treatment are essential for malaria
●​ Other vectors: control.
○​ Anopheles litoralis → ●​ Vector control (Anopheles
coastal Mindanao (esp. flavirostris):
Sulu) ○​ Breeding sites should be
○​ Anopheles maculatus → detected early and
coexists with A. flavirostris, contained.
prefers sunlit streams, ○​ Personal protection
higher altitudes measures are helpful and
○​ Anopheles mangyanus → cost-effective.
same habitats as A. ●​ Insecticide-treated measures:
flavirostris, prefers forest ○​ Use of insecticide-treated
fringe nets (ITNs) with permethrin
●​ Other transmission routes: or deltamethrin.
○​ Blood transfusion from ○​ Long-lasting
infected donors (even insecticide-treated nets
semi-immune, asymptomatic) (LLINs) remain the major
○​ Contaminated needles & vector control strategy.
syringes ○​ Indoor residual spraying
○​ Congenital malaria: (IRS) is used in:
parasites passed ■​ Epidemic situations.
before/during birth from ■​ Areas with stable
infected mother to child​ transmission but
without reduction of
incidence.
■​ Areas with displaced
populations.
Malaria Survey
●​ Personal protection measures:​ ■​ Mefloquine,
doxycycline, or
○​ Wearing light-colored atovaquone/progua
clothing that covers most of nil → for areas with
the body (dark colors attract high chloroquine
mosquitoes). resistance.
○​ Using insect repellents with ●​ Malaria in pregnancy:
DEET ○​ Strategies include:
(N,N-diethyl-m-toluamide, ■​ Use of ITNs.
35% concentration lotion) on ■​ Intermittent
exposed body parts. preventive
○​ Using insect sprays treatment (IPT): at
containing pyrethrum in least 2 preventive
living areas. treatments with an
○​ Using permethrin effective antimalarial
insecticide spray for drug.
clothing. ●​ Vaccine development (ongoing):
●​ Chemoprophylaxis:​ ○​ Sporozoite vaccines.
Protective for travelers with no ○​ Asexual vaccines.
malaria immunity (not 100% ○​ Altruistic /
effective). transmission-blocking
○​ Bite precautions are still vaccines.
necessary even with ○​ Combination vaccines from
antimalarial use. multiple parasite life stages.
○​ Prophylactic drugs must be ●​ Vector control strategies:
taken: ○​ Environmental
■​ For the entire modification.
duration of stay. ○​ Biological control:
■​ Continued 4 weeks ■​ Use of larvivorous
after last possible fish in streams and
exposure (due to rice fields.
possible liver-stage ■​ Bacterial insecticide
emergence). (PG-14 Bacillus
■​ Exception: thuringiensis).
Atovaquone/proguanil ○​ Chemical control:
→ can be stopped 1 ■​ Mosquito repellents.
week after return. ■​ Insecticide-treated
○​ Drug choices: mosquito nets.
■​ Chloroquine → only ●​ Molecular entomology research:
in areas with P. vivax ○​ Stable germline
or low risk of transformation of
chloroquine-resistant Anopheles mosquitoes is
P. falciparum.​ under investigation.​
○​ Genes (e.g., immune
response genes) are inserted
to inhibit parasite
development in mosquitoes.
○​ With the sequencing of
Plasmodium falciparum
and Anopheles genomes,
new research areas for
malaria treatment and
prevention are being
explored