2.

1
25 JULY
malaria 2014
Dra. Malijan
“I can’t change the direction of the wind, but I can adjust my sails to always reach my destination.”
—Jimmy Dean

 Prefers to breed in a slow, flowing, partly shaded

streams that abound in foot hill areas
TOPIC OUTLINE ― Paulo Coelho
 Occasionally, they utilize new habitats such as irrigation,
ditches, rice fields, pools and wells
I. Taxonomic classification
II. Geographical Distribution
 Horizontal flight: 1-2 km
A. Epidemiology in the Philippines o Anopheles litoralis
B. Prevalence in the Philippines  In coastal areas of Mindanao, particularly, Sulu
III. Genus Plasmodium o Anopheles maculates
IV. Transmission  A. flavirostris in the portion of the streams that is
A. Vector exposed to light
V. Life Cycle  Appears to be responsible for the malaria in high
VI. Pathogenesis and Clinical Manifestations
A. Clinical Manifestations
altitudes
a. Three Stages of Classical Malarial o Anopheles mangyanus
Paroxysms  Has same breeding habitat and seasonal prevalence as
b. Classical S/Sx A. flavirostris
B. Pathogenesis  Prefers habitat located in forest fringes
VIII. Malarial Infection LIFE CYCLE
IX. Recrudiscence vs. Relapse
 Asexual cycle
X. Complications
XI. Diagnosis o In humans
XII. Treatment o Consists of Schizogony, which leads into the formation of
XIII. Prevention and Control merozoites and gametogony which leads to the formation
XIV APPENDIX of gametocytes
xv. SAMPLE QUESTIONS  Sexual cycle
o In mosquitoes
Texts in blue were from the book or other sources o Involves schizogony which leads into the formation of
TAXONOMIC CLASSIFICATION sporozoites
 KINGDOM PROTISTA  All four human species of malaria have similar life cycle
o SUBKINGDOM PROTOZOA (Belizario).
 PHYLUM APICOMPLEXA  Except for the presence of hypnozoites (in human liver) for
 CLASS SPOROZOA the species P. ovale and P. vivax (accdg to Dr. Malijan).
o Plasmodium spp.  Hypnozoites are dormant forms in the life cycle of certain
parasitic protozoa that belong to the Phylum Apicomplexa
(Sporozoa) and are best known for their probable
GEOGRAPHICAL DISTRIBUTION
association in the latency and relapse in human malarial
 Tropics
infections caused by P. ovale and P. vivax (pubmed). (so in
 Subtropics
short, they’re just sleeping and waiting for “reawakening”)
 Temperate
 For the diagram, please see appendix…
 1/3 world population (2.2 billion)
PATHOGENESIS and CLINICAL MANIFESTATIONS
 Incidence: 280 million
 10 million affected each year  Once the parasite has invaded the RBCs, cells reduce
 2-3 million die each year deformability.
 Identified by the WHO as one of the three major infectious  In the course of invasion, electron dense submembranous
disease threats, along with HIV and TB (Belizario). structures appear and enlarge and become “knobs”
(important in cell adhesion.
EPIDEMIOLOGY IN THE PHILIPPINES
 Hemoglobin is digested forming Hematin and variant strain-
 65/78 provinces are endemic
specific neoantigens are expressed.
 11.3M Filipinos at risk (14.8%)
 Soluble antigens of P. falciparum are potent inducers of pro-
o Farmers, indigenous groups, miners, forest product
inflammatory cytokines which stimulates the release of TNF
gatherers and soldiers.
or cachexin which causes malarial fever.
 Rank as one of the ten (10) leading causes of morbidity
CLINICAL MANIFESTATIONS
 Highly endemic provinces
o Palawan, Kalinga, Apayao, Ifugao, and Agusan del Sur  INCUBATION PERIOD
o Davao and Compostela Valley o The time between the sporozoite injection and the
appearance of symptoms
MALARIA PREVALENCE: PHILIPPINES
 Typically 8-40 days depending on the species(9days-3years)
 7.3/1000 (1974)
o Plasmodium falciparum
 67-70% due to Plasmodium falciparum
o P. vivax
 30-33% due to P. vivax
o P. ovale
 0.01% due to P. malariae
o P. malariae
Genus Plasmodium
 Depends on the parasite strain, dose of sporozoites
 Group of parasite that causes malaria
inoculated, immune status of the host malariae
 Four species are important to man
chemoprophylaxis history.
o Plasmodium falciparum
 There are no absolute diagnostic clinical features EXCEPT for
o Plasmodium vivax
irregular paroxysms of fever with asymptomatic intervals
o Plasmodium ovale
 PRODROMAL SYMPTOMS
o Plasmodium malariae
o Feeling of weakness and exhaustion, a desire to stretch
 These are pigment producers and are ameboid in shape,
and yawn, aching bones and limbs, loss of appetite,
some being more ameboid than others.
nausea and vomiting a sense of chilliness.
 Asexual stages occur in man, the vertebrate and
3 STAGES OF CLASSICAL MALARIA PAROXYSMS
intermediate host
 Cold Stage
 Sexual stages occur in mosquito, the invertebrate and the
o Starts with a sudden inappropriate feeling of coldness and
definitive host.
apprehension.
TRANSMISSION
o Violent teeth chattering and shaking of the whole body.
 Bite of the female Anopheles mosquito (Why female?
o Intense peripheral vasoconstriction despite increased core
Because males are vegetarian)
temperature.
 Blood transfusion
o These rigors last 15 to 60 minutes
 Accidental needle prick
 Hot Stage
 Mother to fetus
o Flush phase (2-6 hours)
VECTOR o Patient becomes hot and manifests with headache,
 In the Philippines: palpitations, tachypnea, epigastric discomfort, thirst,
o Anopheles minimus var. flavirostris nausea and vomiting, confused and delirious, skin is
 Night biter flushed or h0t

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 malaria

o Temperature is 40-41°C o Abnormal bleeding

 Sweating Phase o Jaundice
o Defervescence or diaphoresis ensues with profuse o Hemoglobinuria
sweating o High fever
o The temperature lowers within the next 2-4 hour sand o hyperparasitemia
symptoms diminish OTHER SIGNS OF SEVERE MALARIA
Note: the typical duration of the typical attack is 8-12hours.  Severe anemia
 Thrombocytopenia
CLASSICAL SIGNS AND SYMPTOMS  Renal failure
 TRIAD OF  Pulmonary edema
o Anemia  Hypoglycemia
o Fever and chills  Circulatory collapse/ shock
o Splenomegaly COMPARISON OF SIGNS AND SYMPTOMS OF SEVERE
PATHOGENESIS MALARIA IN ADULTS AND CHILDREN
 Altered RBC surface + Host’s immunological response Signs and Adults Children
alteration in the regional blood flow and vascular epithelium, Symptoms
altered biochemistry, anemia, hypoxia History of cough uncommon Common
 Please see appendix for pathophysiology… Convulsions common Very common
MALARIAL INFECTION Duration of 5-7 days 1-2 days
 Plasmodium falciparum illness
 Plasmodium vivax Resolution of 2-4 days 1-2 days
 Plasmodium ovale coma
 Plasmodium malariae Neurological <5% >10%
 Simian strain sequelae
o Plasmodium Knowles Jaundice common Uncommon
o Plasmodium cynamolgi Pretreatment uncommon common
o Plasmodium simium hypoglycemia
 Is there difference in the patterns of illness among the Pulmonary uncommon Rare
species? edema
P. P. P. P. Renal failure common Uncommon
falciparum vivax ovale malariae CSF opening Usually normal Usually raised
INCUBATION 2 weeks 2 2 30-40 pressure
PERIOD (8-15 days) weeks weeks days (18- Respiratory sometimes Common
(12-20 (11-16 40days) distress(acidosis)
days) days) Bleeding/clotting Upto 10% Rare
PERIOD OF 36-48 48 48 72 hours disturbances
SCHIZOGONY hours hours hours Abnormality of rare More common
TYPE OF Malignant Benign Benign quartan brain
FEVER tertian/ tertian tertian
subtertian
TYPES OF Both young young young Mature, PATIENTS SUSPECTED OF MALARIA
RBC and old old  History of chills, fever and sweating
INFECTED (at least hindi  History of blood transfusion within the past 6 months
siya choosy)
 History of living in endemic areas for malaria for the past
 Please see appendix for the types of fever… two years.
RECRUDESCENCE VS RELAPSE DIAGNOSIS
 RECRUDESCENCE
 Microscopic identification of the malarial parasites in
o The renewal of parasitemia and/or clinical features arising thick and thin blood smears stained in with Giemsa or
from persistent undetectable asexual parasitemia in the
Wright’s stain: Gold stain.
absence of an exo-erythrocytic cycle o OBTAIN SMEARS EVERY 6-8 HOURS.
o P. falciparum (1 year)
 Quantitative Buffy Coat (QBC)
o P. malariae (30-40 days) o Uses a specially prepared capillary tube coated with
o Accdg. To Dra. Malijan, P. vivax and P. ovale may also acridine orange: only to screens the presence of malarial
have this. parasites
 RELAPSE  Rapid Malaria Diagnostic (tests RDTs)
o Renewed asexual parasitemia in the following a period in
TREATMENT
which the blood contains no detectable parasites
 Main uses of antimalarial drugs
o This occurs in P. vivax and P. ovale infections, as a result
o Protective (prophylactic
of the reactivation of hypnozoites of the parasite in the
o Curative (therapeutic)
liver
o preventive
o P. vivax (2-3 years)
 Chloroquine has been the mainstay of antimalaria treatment.
o P. ovale (usually the same with P. vivax) (idol niya si vivax
ginagaya niya kaya madalas pareho sila!!!)
 Sulfadoxine-pyrimethamine combination or quinine-areas
COMPLICATIONS with high levels of chloroquine resistance.
 CEREBRAL MALARIA: complication of severe P. falciparum  Quinine Is the drug of choice for malaria in PREGNANCY.
malaria.  Artimisinin and its derivatives (Qinghaosu derivatives)
o A diffuse encephalopathy with loss of consciousness  Parenteral
 Consciousness ranges from stupor to coma  Multidrug-resistant malaria is treated by combination of
 Onset can be gradual or rapid, unresponsive to pain, mefloquine and sulfadoxine-pyrimethamine, halofantrine or
visual and verbal stimuli any Qinghaosu derivatives.
o Associated with sequestration in cerebral vasculature. PATIENTS WHO SHOULD BE HOSPITALIZED
SYMPTOMS OF SEVERE P. falciparum malaria  Positive for the asexual stage of Plasmodium falciparum
 The first probable symptom is prostration a condition  Patients with complications or life-threatening malaria
characterized by confusion, or drowsiness with extreme  Children regardless of the strain of Plasmodia seen in
weakness then one or any combination of the following: peripheral blood smear
o Cerebral malaria  Pregnant women.
o Generalized convulsions PREVENTION AND CONTROL
o Severe normocytic anemia  Early diagnosis and prompt treatment of malaria is essential
o Metabolic acidosis with respiratory distress for control
o Fluid and electrolyte disturbances  Personal protective measures against mosquito bites are
o Acute renal failure also helpful.
o Acute pulmonary edema and adult respiratory distress o Staying in well screened areas
syndrome (ARDS) o Use of mosquito nets tucked under mattress
o Circulatory collapse, shock, septicemia, also called algid o Use of insect repellants
malaria  Chemoprophylaxis may be protective in travelers

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o Prophylactic drugs should be taken with good compliance
for the duration of stay and should be continued for 4
weeks after the last possible exposure.
o An exception would be treatment with atovaquone or
proguanil which can be stopped 1 week after return
o Chloroquine is only recommended for areas where
malaria is exclusively due to P. vivax or where there is a
low risk of chloroquine-resistant P. falciparum.
o Travelers going to areas with high level of resistance to
chloroquine may use mefloquine, doxycycline or
atovaquone/proguanil.
 Work is on going for the development of an effective malaria
vaccine. Among the vaccine types being developed are the
sporozoite vaccines, asexual vaccines, and the altruistic or
transmission-blocking vaccines. Combination vaccines
derived from multiple parasite life stages are also being
developed.

APPENDIX

The malaria parasite life cycle involves two hosts. During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host .

Sporozoites infect liver cells and mature into schizonts , which rupture and release merozoites . (Of note, inP. vivax and P. ovale a dormant stage

[hypnozoites] can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later.) After this initial replication in the liver (exo-

erythrocytic schizogony ), the parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogony ). Merozoites infect red blood cells .

The ring stage trophozoites mature into schizonts, which rupture releasing merozoites . Some parasites differentiate into sexual erythrocytic stages

(gametocytes) . Blood stage parasites are responsible for the clinical manifestations of the disease.
The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal . The parasites’
multiplication in the mosquito is known as the sporogonic cycle . While in the mosquito's stomach, the microgametes penetrate the macrogametes generating
zygotes . The zygotes in turn become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop into oocysts .
The oocysts grow, rupture, and release sporozoites , which make their way to the mosquito's salivary glands. Inoculation of the sporozoites into a new human
host perpetuates the malaria life cycle

NOTE: SINCE THERE IS NO HYPNOZOITE SHOWN IN THE DIAGRAM ABOVE, LET US JUST REMEMBER THAT THIS STAGE IS SEEN ONLY IN P. vivax and
P. ovale AND THAT THIS USUALLY COMES FROM THE SPOROZOITES IN THE LIVER (SPOROZOITES IN THE LIVER MAY DEVELOP INTO HYPNOZOITES
AND SCHIZONTS).

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 malaria

DIAGRAM THAT SHOWS THE PATTERNS OF FEVER OF THE PLASMODIUM SPECIES

COMPARISON OF THE MORPHOLOGICAL FEATURES OF MALARIAL PARASITE

PARAMETERS P. falciparum P. vivax P. ovale P. malariae

(malignant tertian) (benign tertian) (benign tertian) (quartan

Infected RBCs Normal; multiple Larger than normal, Somewhat larger Normal or slightly
infection of RBC very pale, often bizarre; than normal, often smaller; sometimes
common schuffner’s dots are with fringed or darker in early
often present; multiple irregular edge, and stages; multiple
infection of RBC not oval in shape; infection of RBCs are
uncommon schuffner’s dots rare.
appear even with
younger stages;
stains more readily
and deeply than in
P. vivax
Small trophozoite (early Same as P. vivax but Signet-ring form Small, darker in Same as P. vivax but
rings) with small threadlike with heavy red dot color and generally with blue cytoplasmic
blue cytoplasmic and blue cytoplasmic more solid than circle, smaller, thicker
circle with 1 or 2 small ring those of P. and heavier.
red chromatin dots; falciparum;
double chromatin schuffner’s dots
common; marginal regularly present in
forms common almost 100% of
infected cells
Growing trophozoite Remains in ring form but Like small trophozoite, Resembles closely Chromatin rounded,
grows resembling small as above, with same stages of P. or elongated;
trophozoite of P. vivax in increased cytoplasm malariae but is cytoplasm compact or
size; usually oldest and ameboid activity; considerably larger; in narrow band across
asexual stage seen in small yellowish brown pigment is lighter cell; dark brown
peripheral blood pigment granules in and less granules may have
cytoplasm, increasing conspicuous peripheral
with age of parasite arrangement
Large trophozoite Seldom present Large mass of Seldom present Chromatin often
chromatin; loose elongate, indefinite in
irregular or close outline; cytoplasm
compact cytoplasm dense, compact, in
with increasing rounded oblong or
amount of fine brown band forms; pigment
pigment; parasite granules larger,
parasite fills cells in darker than P. vivax;
30-40hours. parasite fills cells
frequently.
Schizont (pre-segmenting) Not present Chromatin divided; About 25% of Same as P. vivax
cytoplasm shows infected cells are except the parasite is
varying degrees of definitely oval smaller, shows less
separation into shaped; usual chromatin division,
strands and particles; picture is that of a more delayed
pigment collects in round parasite in clumping of pigment
parts of the parasite the center of an
oval cell; many
cells with indefinite
fringed outline;

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 malaria

pigment is lighter
and less coarse
than in P.
malariae
Schizont (mature) Rarely present: 8-24 12-24 merozoites; Usually 8 6-12 (average 8-10)
merozoites; smaller than pigment in 1-2 clumps merozoites merozoites in rosette
other species parasite almost fills arranged around a form; parasite
enlarged cells central block of almost fills the cells.
pigment
Gametocyte Present in peripheral Microgametocyte: light Distinguished form Same as P. vivax
blood stream; similar to red to pink chromatin, P. malariae by size except smaller; fills
P. vivax; crescent or diffuse, central; gives of infected cells and or almost fills cell
sausage shape tint to light blue by schuffner’s dots;
cytoplasm; yellowish less easy to
brown pigment differentiate from
throughout cytoplasm; P. vivax;
usually round and
about the size of
normal RBC
Macrogametocyte:
small, compact, dark
red eccentric
chromatin; cytoplasm
dark blue, no
vacuoles, abundant
dark brown pigment
scattered throughout
the cytoplasm
Stages In peripheral blood Ring forms All stages are present All stages are All stages are present
gametocytes; other present
stages rare
Length of asexual cycle 48 hours or less 48 hours 48 hours 72 hours

SAMPLE QUESTIONS
1. What species of mosquito is the vector of malaria in
Mindanao, particularly in Sulu?
2. What stage in the Plasmodium life cycle occurs in
man? In mosquito/vector?
3. What is the dormant form in the life cycle of certain
species of Plasmodium which is responsible for
RELAPSE?
4. What are the species that exhibit the dormant form in
question no. 3?
5. What stage in the classical malarial paroxysms is
characterized by having a temperature of 40-41
degrees celcius?
6. What is the drug of choice for pregnant malarial
patient?
7. What stage in the classical malarial paroxysms starts
with sudden inappropriate feeling of cold and
apprehension?
8. In this phase of classical malarial paroxysm,
defervescence and diaphoresis ensues with profuse
sweating.
9. This is the renewal of parasitemia and/or clinical
features arising from persistent undetectable asexual
parasitemia in the absence of an exo-erythrocytic
cycle.
10. The complication of severe P. falciparum malaria.

ANSWERS: Anopheles littoralis; asexual/sexual;hypnozoite; P.

vivax and P. ovale; hot phase; quinine; cold phase; sweating
phase; recrudescence; cerebral malaria

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