MALARIA

Dr. Bonifacio

Note: Italicized text were taken directly from the old trans by Gabaldon

PLASMODIA
Class Sporozoa
Only organism under this class that has no organ for
motion
Basis of diagnosis: Any stage of parasite in
peripheral smear
Malaria: mal-bad; aria-air
Only caused by female Anopheles (feed on blood)

Epidemiology and Features

HUMAN STRAINS
I.
Plasmodium falciparum
a. Associated with MORTALITY
b. Fatal; 67-70%
II.
Plasmodium vivax
a. Associated with MORTALITY and
MORBIDITY
b. 30-35%
III.
Plasmodium malariae
a. 0.01-1%
b. BENIGN
c. Found only in some isolated places in
Mindanao and Palawan
IV.
Plasmodium ovale
a. Not common in the Philippines
b. Benign
c. Common in African countries
Examples (Ddx):

Patient from Visayas possible strains are Vivax

and Falciparum

Patient is soldier consider the 3 strains

Geographical Distribution
Tropics
Subtropics
Temperate
1/3 of world population (2.2 Billion)
Incidence: 280 million
10 million affected each year
2-3 million die each year
RP Prevalence
7.3/1000 population (1974)
67% to 70% due to P. falciparum (Patient must be
hospitalized for monitoring)
30-33% due to P. vivax
0.01% due to P. malariae

Mode of Transmission
Anopheles minimus flavirostris
Anopheles mangyanus
Bite of an infected female Anopheles mosquito
(night biter)
No transovarian transmission
Blood transfusion (100% transmission)
Accidental needle prick (IV drug users)
Mother to fetus (congenital malaria)

*Female utilize blood for progeny

VERTICAL TRANSMISSION

Mother to fetus
HORIZONTAL TRANSMISSION

Sexual contact

NON HUMAN STRAIN/SIMIAN STRAINS

Parasite of monkeyscan also infect human

P. knowlesi Palawan and Mindanao

P. cynamolgi

P. simium

Malaria Data 2000 Summary

Population at risk for malaria (11,337,000)
Incidence per 1000 population: 0.48
Number of malaria deaths: 536
Number of patient tested for malaria: 444,668
Number of confirmed cases

*Note:

Malaria Detection by Morphology

Thick and Thin Smear Gold Standard for
Diagnosis; 50-55% (+)
*low sensitivity
*THIN SMEAR
o
Morphology
o
Not to be used in light infection
*THICK SMEAR
o
If degree of parasitemia is too low
o
Density of Parasite
Red Staining substance: CHROMATIN DOTS
Bluish substance adjacent to red substance:
CYTOPLASM
Brown substance: HEMOZOIN

Stain used to identify Malarian Parasite:

Wright and Giemsa Stain: Routine procedure

Fields Stain: Mass Staining

Life Cycle
Infective Stage Transfer Stage
Pathogenic Stage Produce tissue alteration; signs and
symptoms
Diagnostic Stage Any stage seen by naked eye; Basis for
Diagnosis

Macrogametocyte
Macrogamete (1:1) inside body of mosquito

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MALARIA

Dr. Bonifacio

Note: Italicized text were taken directly from the old trans by Gabaldon

+
1 microgamete (1:6:12)
Differentiation/ Exflagellation
6-12 microgametes (only 1 is needed to fuse with
macrogamete; the rest will be destroyed)
Fertilization

1. young SCHIZONT
2. growing SCHIZONT
3. mature SCHIZONT
Burst
Release of Chromatin Dots

ZYGOTE (Product)

Infect another RBC

Ookinete

Vicious cycle

Oocyst

Differentiation of some merozoites to

macro/microgametocyte

Ripe/Mature
Sporozoite Inside (30,000 sporozoite)

ASEXUAL=SCHIZOGONY=Schizont=Intermediate Host=MAN
SEXUAL=SPOROGONY=Sporozoite=Definitve Host=MOSQUITO

Rupture
Sporozoite + Saliva of Mosquito
Night (night biter)
Sporozoites In the venous Circulation
Liver
Exo-erythrocytic
phase;
Pre-erythrocytic
Phase;
Liver Phase;
Tissue Phase

30 mins-1 hour

Develop into:
1. young trophozoite
2. growing trophozoite
3. mature trophozoite
Young Schizont
Growing Schizont

Mature Schizont
Rupture
(Chromatin Dots released in circulation)
Release of Merozoites
ERYTHROCYTIC PHASE
To become viable
Infect RBC
DEVELOPMENTAL STAGE
1. young trophozoite RING FORM
2. growing trophozoite
3. mature trophozoite single chromatin dot will split

*Young Trophozoite Source

Trophozoite

Merozoite in Eryhtrocytic Phase

Infective Stage to MAN
(Intermediate Host)
Infective Stage to MOSQUITO
(Definitive Host)

SPOROZOITE
GAMETOCYTE

MAN: Schizogony

Liver Phase / Tissue Phase / Exoerythrocytic /

Preerythrocytic Stage
o
Bite by mosquito (harboring of
sporozoite)
o
Takes only 30 min-1 hr to start first stage
o
All stages develop in the liver; hepatic
schizogony
o
Patient is asymptomatic

Erythrocytic Stage
o
Starts when mature schizont rupture and
releasethe merozoites in circulation
o
Vicious life cycle occurs
o
No secondary pre-erythrocytic stage
occurs (parasites will not go back to liver)
o
AS an alternative to schizogony, some of
the parasites will undergo a sexual cycle
and terminally differentiate into either
micro or macrogametocyte
o
Gametocytes do not cause pathology in
the human host and will disappear from
the circulation if not taken up by
mosquito
MOSQUITO: Sporogenic Phase

Gametogenesis ; formation of micro and

macrogametesinduced when the gametocytes
are ingested by a mosquito

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MALARIA

Dr. Bonifacio

Note: Italicized text were taken directly from the old trans by Gabaldon

Macrogametes (1:1)
Microgametes (1:6:12) 3 rounds of replication;
only 1 microgamete is utilized to fertilize
macrogamete
EXFLAGELLATION: process in which thrashing
flagella emerges from the microgametes
Gametes fuse to become a ZYGOTE which first
develops into an OOKINETE and then becomes an
OOCYST where SPOROGONY takes place
Oocyst undergo an ASEXUAL replication
(SPOROGONY), which culminates in the production
of several thousand SPOROZOITES. This generally
takes 10-28 days, depending on species and
temperature.
Upon maturation, the oocyst ruptures and releases
the sporozoites which cross the basal lamina into
the hemocoel of the mosquito
The sporozoites are motile and have an ability to
specifically recognize the SALIVARY GLANDS.
Sporozoites will then invade and transverse the
salivary gland epithelial cells and come to lie within
its lumen
Some sporozoites will be expelled into the
vertebrate host as the mosquito takes a blood meal,
thus reinitiate the infection in the vertebrate host

Plasmodium vivax
All stages seen in peripheral smear
Only strain that causes enlarged RBC
May have multiple infection
Young trophozoite
o
RING FORM; no enlargement; 1
chromatin dot
Growing trophozoite
o
1/3 occupied by blue cytoplasm; irregular
in shape; 1 chromatin dot; from this
stage onwards, there is RBC enlargement
Mature trophozoite
o
2/3 bluish cytoplasm occupied; 1
chromatin dot
Young Schizont
o
2 chromatin dots
Growing Schizont
o
2-12 chromatin dots
Mature schizont
o
12-24 chromatin dots in cluster; the one
that ruptures in vivo (circulation);
releases merozoites (chromatin dots)
invading other RBC
Gametocytes
o
being developed after several weeks;
INFECTIVE STGE; chromatin dots are now
called CHROMATIN GRANULES
o
Macrogametocyte

Female

Chromatin
granules
on
periphery

Compacted at edge
o
Microgametocyte

Male

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MALARIA

Dr. Bonifacio

Note: Italicized text were taken directly from the old trans by Gabaldon

Chromatin granules at the

center

Loose arrangement
The mosquito has to have both macrogametocyte
and microgametocyte to be able to infect

Has macerated area, fimbriated RBC

IRREGULAR PAROXYSM

Caused by P. falciparum but also with mixed

infection
COMPARISON:

Plasmodium malariae
All stages seen in peripheral smear
Normal size RBC
Same stages and development
Growing Schizont
o
2-6 chromatin dots
Mature Schizont
o
6-12 chromatin dots
o
Rosette arrangement/daisy-pattern
o
Peripheral arrangement
o
With brown substance: Hemozoint
pigment
product
of
parasite
pathognomonic
Young schizont: chromatin dots
Presence of BAND form
o
Growing trophozoite stage
o
Seen in 15% of parasite in growing
trophozoite
Plasmodium falciparum
Only ring form and gametocyte seen in peripheral
smear
Normal size RBC
Ring Form
o
Multiple infection (more than 1 parasite
in a single infected RBC)
o
2 chromatin dots
o
PLEOMORPHIC

assume
any
configuration;
exclamation
point,
comma, swallow or accole pattern
Gametocyte
o
Mature schizont not usually seen in
peripheral smear. If mature schizont is
seen serious complication worst
100,000/m3 degree of infection
18-24 chromatin dots
Banana-shaped/crescent-shaped presence of
chromatin granules
Mixed infection: more than 1 strain of parasite

PERIOD OF SCHIZOGONY

Period of height from 1 fever to next height of fever

MEROZOITE

Pathogenic stage of all plasmodian; released AFTER

height/peak of fever
STIPPLINGS

Cytoplasmic destruction in RBC

JAMES DOT

Stippling found in P. ovale

P. ovale

Incubation
period
Period of
Schizogony
(rupture of
mature
schizont)
Type of fever

Affected red
cells
Effect in red
cells
Stipplings
(cytoplasmic
destruction)
Stages seen in
PBS

Degree of
Parasitemia
# of Chromatin
Dots in Mature
Schizont Stage
Other
Diagnostic
features

P.
falciparum
2 weeks

P. vivax

P. malariae

2 weeks

30-40 days

36-48 hrs

48 hrs

72 hrs

Malignant
Tertian/
Subtertian
Irregular
Young and
Mature
Not
enlarged
Maurers /
Christofers
bodies
Young
trophozoite
and
Gametocyte
100,000/cu
mm
18-24 up to
32
cluster of
grapes
Crescent/
banana
shaped
gametocyte;
Knob
formation
at the
surface of
an infected
RBC

Benign
Tertian
Regular

Quartan
Regular

Young RBC
only
ENLARGED
Schuffners
dots

Mature
RBC only
Not
enlarged
Ziemmans
dots

All stages

All stages

50,000/cu
mm
12-24
Cluster of
grapes

15,000/cu
mm
6-12
Rosette
pattern
Presence of
Band Forms

Malaria Paroxysm
COLD STAGE
o
Feeling of intense cold
o
Vigorous shivering
o
Lasts for 15-60 minutes
HOT STAGE
o
Intense heat
o
Dry burning skin
o
Throbbing headache
o
Usually mid day
o
Lasts 2-6 hours
HYPERHYDROSIS STAGE (Sweating Stage)

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MALARIA

Dr. Bonifacio

Note: Italicized text were taken directly from the old trans by Gabaldon
o
o
o
o

Profuse sweating
Declining temperature
Exhausted and weak sleep
Lasts 2-4 hours

o
o

Figure. A typical pattern of temperature (fever) in

relation to blood-stage schizogony for the human

malarial parasites. The fever paroxysm corresponds
to the period of infected erythrocyte rupture and
merozoite invasion.

*Rupture of Schizont = increased temperature

= usually mid-day

Recurrence of Paroxysm
RECRUDISCENCE
(Recurrence)
RELAPSE

P. falciparum (1 year)
P. malariae (30-40 years)
P. ovale
P. vivax (2-3 years)

RECRUDISCENCE
o
P. falciparum and P. malariae
o
No hypnozoite
o
All schizonts rupture

Parasitemia falls below detectable levels

and then later increases to a patent
parasitemia
Hide in trophozoites stimulation by
parasites in trophozoites
Some of the parasites that rupture
another paroxysm

RELAPSE
o
P. ovale and P. vivax
o
Some of the sporozoites do not
immediately undergo asexual
reproduction but enter a dormant phase
known as HYPNOZOITE
o
Hypnozoite can reactivate and undergo
schizogony at a later time resulting in
relapse
o
Reactivation of infection via hypnozoites
o
Mature schizont: some may remain
dormant in the LIVER via antigenic
stimulation release of chromatin
dots/merozoites rupture and release
Diagnosis
Thin and Thick Smear (Gold Standard)
o
Low sensitivity/parasitemia
o
Parasite density
Quantitative Buffy Coat (Use of Acridine orange)
affinity to DNA
o
Definitve diagnosis
Fluorescent Ab Technique
o
More sensitive
Immunochromatography
o
Malarial strips
o
Rapid test but NOT reliable; sensitivity
only 30-65%
ELISA
o
Used to those who are already exposed
o
For centralized screening and antibody
screening
Serologic: Antigen and Antibody Screening
o
Best screening for volunteer donor

**BEST TIME TO COLLECT BLOOD: BEFORE height of

temperature different stages can be seen
*If blood is collected AFTER height of fever: Ring forms only
*If blood is collected at the height of fever: Rupture of
schizontmerozoitesmistaken as platelets

Treatment
CQ + SP
Artemethen Lumefantrine (AL)
Quinine (QN) in combination with either
Tetracycline or Doxycycline or Clindamycin
Artesunate (AS) suppository
ACT (Artemisinin) usedfor all P. species; mixed
infection

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MALARIA

Dr. Bonifacio

Note: Italicized text were taken directly from the old trans by Gabaldon

Regimen A: Chloroquine, DOC

Regimen B: Quinine (can only be administered
parenterally)
Liver parasite:Primaquine (AE: triggers hemolysis)
o
P. vivax
o
P. ovale
Complete Drug: Regimen A + Primaquine
Chemoprophylaxis
NON IMMUNE
o Persons travelling to an endemic area
SEMI IMMUNE
o
Those who came in an endemic area but
have been away for more than 5 years
PRIMIGRAVID
o
Living in an endemic area for malaria; 1st
time pregnancy
Patients Suspected of Malaria
History of Chills, Fever, Sweating
History of Blood transfusion within the past
6months
History of living in an endemic area for the past 2
years
Patients who should be Hospitalized
(+) for the asexual stage of P. falciparum;
mandatory
Patient showing complication/life-threatening
malaria
Children regardless of the strain of Plasmodia seen
in the PBS
Immunocompromised
Pregnant women (common complication is
hypoglycemia) + existing infection

Conatal or Neonatal Malaria

During active labor only
Parasitemia documented after 7 days but not more
than 28 days of life
Manifestations observed in the later course of the
disease
Malaria in Pregnancy
Avoid primaquine since the drug may compromise
the fetus
Palpate liver and spleen for organomegaly
Paper-white conjunctiva
Yellow sclera
Black urine
Life-Threatening Malaria
Parasites more than 100,000 cu mm or multiple
infection <5% in PBS; presence of mature schizont
stage in PBS
Hemolysis where Hgb is >7gms; Hct > 20%
immediate blood transfusion
Jaundice
Hemorrhage DIC
Hypoglycemia with blood sugar level of 60 mg/dL or
less seizure
Clinical shock; kidney failure
Hyperthermia (40-42 C) accompanied by seizure
Prevention
Health education
Eradication of mosquitoes
o
Insecticide
o
Repellent
o
Mosquito nets

Complicated Malaria
(+) for P. falciparum + drug resistance (R2 or R3)
Life threatening condition
G6PD in Malaria
There are drugs that may trigger hemolysis in
patients with G-6PD deficiency
Peripheral Blood smear 20% Heinz bodies (red
staining dots in the PBS) significant for the diagnosis
of G-6PD
G-6PD prevalent in Visayas, Panay Island, and Iloilo
Primaquine destroys parasites in the liver,
however it also triggers hemolysis in G-6PD patients
Congenital Malaria
Parasitemia documented within 7 days of life
Manifestations observed several weeks after prepatent period

Page 6 of 7
palindrome.2012

MALARIA

Dr. Bonifacio

Note: Italicized text were taken directly from the old trans by Gabaldon

**P. malariae = NEPHROTIC SYNDROME = better prognosis

than nephritic syndrome
**P. falciparum = NEPHRITIC SYNDROME (immune complex
nephritis) bad prognosis

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