Plasmodium

Plasmodium falcifarum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
 Malaria is still considered
the most important
parasitic disease affecting
man.
 Transmitted by a bite of
an infected female
mosquito belonging to the
genus Anopheles.
 Their asexual cycle
occurs in man , while
sexual cycle occur is
Anopheles mosquito and
definitive host.
Parasite Biology
 The asexual cycle in humans consists of
schizogony, which leads to the formation of
merozoites , and gametogony, which leads to
the formation of gametocytes.
 The sexual cycle in the mosquito involves
sporogony, which leads to the sporozoites.
 The life cycle of all 4 human species of
malaria are similar.
 Life Cycle

Sexual
stage
(Sporogony)
Asexual stage
(Schizogony)
 Infected female Anopheles mosquito bites and
sucks blood from the human host.
 In the process, salivary fluids containing sporozoites
are also injected.
 These sporozoites , the infective stage of the
parasites, are immediately carried to the liver and
enter the parenchymal cells.
 The parasites then commence exoerythrocytic
schizogony, which produces the merozoites in
varying duration and amounts, depending on the
species.
 Merozoites proceed to the peripheral blood
to enter the erythrocytes,
 Some merozoites of P.vivax, and P. ovale,
re-invade the liver cells forming hypnozoites,
while other species do not.
 These dormant exo-erythrocytic forms may
remain dormant for years,
 Within rbc, the merozoite grows as a ring form
developing into a trophozoite.
 The trophozoite has an extended cytoplasm and a
large chromatin mass, which further subdivided to
form more merozoites,
 The parasitophorous vacuolar membranes (PVM)
within the mature red cells and modify the structural
and antigenic properties of these cells.
 The malarial parasite feed on hemoglobin resulting
in the production of pigment,
 Some merozoites develop into microgametocyte(male) and
macrogametocytes(female) which are picked up by female
mosquitoes for completion of the life cycle.
 In the gut of the mosquito, the male gametocytes exflagellate and
produce 8 sperm-like microgametocytes which may fertilize the
female macrogametocyte to form a zygote.
 The zygotes becomes motile and penetrates the mosquito gut as
ookinete, which then develops into an oocyst.
 The oocyst grows and produces sporozoites , which escape
Pathogenesis and Clinical
Manifestations
 The interval of time from sporozoite injection
to detection of parasites in the blood is
prepatent period.
 Depending on species involved, range from
11 days to 4 weeks.
Average prepatent period.
 P.falcifarum - 11 – 14 days
 P. vivax – 11-15 days
 P. ovale – 14 – 26 days
 P. malariae – 3 – 4 weeks
Incubation period
 The time between sporozoite injection and
the appearance of clinical symptoms .
 Typically 8 – 40 days depending on species
involved.
 P. falcifarum – 8 – 15 days
 P. vivax – 12-20 days
 P. ovale – 11-16 days
 P. malariae- 18 -40 days
 The incubation period may range from 9 days to 3
years, depending on :
 species strain
 dose of sporozoite inoculated
 Immune status of the host
 Host’s malaria chemoprophylaxis histtiory
 Partial or incomplete prophylaxis may prolong incubation
period several weeks after termination of medication.
 Any person who has traveled to a malaria-endemic area
must be considered at risk of developing malaria up to 2
years or longer after leaving the area.
 No absolute diagnostic clinical features of
malaria except for the regular paroxysms of
fever with asymptomatic intervals.
Prodromal symptoms:
 Feeling of weakness and exhaustion
 Desire to stretch and yawn
 Aching bones
 Limbs
 Loss of appetite
 Nausea
 Vomitting
 Sense of chilliness
At the onset, symptoms:
 Malaise
 Backache
 Diarrhea
 Epigastric discomfort
Classical malarial paroxysm
( stages)
 Cold stage – starts with a sudden inappropriate
feeling of coldness and apprehension
 Hot stage – Flush phase, patient becomes hot and
manifests with headache, palpitations, tachypnea,
epigastric discomfort, thirst, nausea and vomitting (
40-41oC or more).
 Sweating stage, defervescence or diaphroresis
ensues with the patient manifesting with profuse
sweating.
COMPLICATIONS (p. 89
Chapter 4 Markell and Voges’)
 Vivax, ovale, quartan malaraia – benign
 P. falcifarum – rapidly build up
 Chronic malariae infections- immune complex
deposition
Complications ( p. 89)
 Cerebral malaria
 Anemia
 Renal disease
 Blackwater fever
 Dysenteric malaria
 Algid malaria
 Pulmonary edema
 Tropical splenomegaly syndrome
 Hyperparasitemia
 Hypoglycemia
Cerebral malaria
The Classic periodicity of
attacks.
 Determined by length of erythrocytic cycle”
 P.falcifarum – 48 hours
 P. vivax and P.ovale – paroxysms occur on
alternate days
 P. malariae – occur every 72 hours, causing
paroxysms on days 1 and 4, (quartan malaria)
Erythrocytes infected
 The non-falcifarum species infect erythrocytes
only at a certain age:
 P. vivax and P.ovale – infect only young rbc
 P. malariae – infects only aging cells

 P. falcifarum – infect rbc of all ages

Recrudence or relapse
 Recrudence – renewal of parasitemia and/or
clinical features arising from persistent
undectable asexual parasitemia in the
absence of exo-erythrocytic cycle.
 Relapse – is the renewed asexual
parasitemia following a period in which blood
contains no detectable parasites
parasites.Occur with P.vivax and P. ovale
infections, results from the reactivation of
hypnotic ofrms of parasite in the liver.
Pathological process in
malaria (Erythrocytic cycle)
 The rbc reduce their deformability , in the course of
the invasion, electro-dense submembraneous
structures appear and enlarge (knobs), which are
important in cytoadhesion.
 Infected rbc also undergo altered membrane
transport mechanisms.
 The combination of altered red cell surface
membranes and the host’s immunological response
to the parasite antigens brings about pathologic
changes such as alteration in regional blood flow
and vascular epithelium.
 In severe form of malaria, impairment of
consciousness and other signs of cerebral
dysfunction, such as delirium and generalized
convulsions are commonly observed.
 Cerebral malaria generally manifest with diffuse
symmetric encelopathy.
 Respiratory findings are also major feature of severe
malaria.
 Incidence of acute renal failure( falcifarum malaria).
 Malaria in pregnancy increases the risk of
maternal death, maternal anemia, intrauterine
growth retardation, spontaneous abortion,
stillbirth, and low birth weight with associated
risk of neonatal death.
 Falcifarum malaria in a young child is
considered a medical emergency for it may
be rapidly fatal.
 Not everyone infected with malaria parasite
becomes seriously ill and dies. In areas
where endemicity is stable, repeated
exposures to the parasite lead to specific
immunity.
 Poor prognostic factors in falcifarum malaria
include hyperparasitemia, defined as
peripheral count more than 250,000/µl or
more tha 5% of the RBC’s infected.
Diagnosis
 Microscopic examination –
thick and thin blood smears
stained with Giemsa or
Wright’s stain (gold standard)
 Specimens may be taken ant
time and all blood stages of the
parasite may be found.
 In falcifarum malaria, only the
ring forms may be found, but
10 days after the symptoms
begin, gametocytes may be
found as well.
 Every 6-8 hours is usually
appropriate in obtaining
smear.
 Quantitative Buffy Coat (QBC) method uses a
specially prepared capillary tube coated with
acridine orange. Malaria parasite take up the stain
and appear bright green and yellow when viewed on
fluorescent microscope (screening)
 Malaria rapid diagnostic tests (malaria RDTs).
 Serological test but presently available method are
not capable of making a definite diagnosis of acute
malaria.
 Comparison of
Morphological features
of malaria parasites
Plasmodium falcifarum
(malignant tertian
 Infected rbc
 Normal ; multiple
infection of rbc very
common
Plasmodium falcifarum

Ring-form trophozoites of P. falciparum in a thick blood smear.

Plasmodium falcifarum

Ring-form trophozoites of P. falciparum in a thin blood smear.

Plasmodium falcifarum
(malignant tertian)
 Small trophozoite (early
ring)
 Growing trophozoite
 Large trophozoite
Plasmodium falcifarum
(malignant tertian)
 Schizont (mature)
 Rarely preseny; 8-24
merozoites; smaller
than other species
Plasmodium falcifarum
(malignant tertian)

Schizonts of P. falciparum in a thin blood smear.

 . A mature schizont
usually fills about 2/3 of
the infected RBC.
 Plasmodium falcifarum
(malignant tertian)
 Gametocyte
 Crescent or sausage
shape

Gametocytes of P. falciparum.
Figs. 27, 28: Mature macrogametocytes (female);
Figs. 29, 30: Mature microgametocytes (male).
Plasmodium falcifarum
(malignant tertian)

Gametocyte of P. falciparum in a thin blood smear. Also seen in this image are ring-form
trophozoites and an RBC exhibiting basophilic stippling (upper left).
Plasmodium vivax (benign
tertian)
 Infected rbc
 Larger than normal;
pale, often bizarre
 Schuffner’s dots are
often present
 Multiple infection of rbc
not uncommon
Plasmodium vivax (benign
tertian)
 Small trophozoite (early
rings)
 Signet-ring form with
heavy dot and blue
cytoplasmic ring
 Plasmodium vivax (benign
tertian)

Trophozoite of P. vivax in a thick blood smear.

Trophozoite of P. vivax in a thin blood smear. Note the amoeboid appearance,
enlarged infected RBC and Schüffner's dots.
Plasmodium vivax (benign
tertian)

: Trophozoites of P. vivax in a thin blood smear. Note the amoeboid

appearance and Schüffner's dots
Plasmodium vivax (benign
tertian)
 Schizont
 12-24 merozoites
 Pigments in 1-2
clumpds
 Parasite almost fills
enlarged cells
Plasmodium vivax (benign
tertian)

Schizonts of P. vivax in thick blood smears.

Plasmodium vivax (benign
tertian)

Schizonts of P. vivax in thin blood smears.

Plasmodium vivax (benign
tertian)
 Gametocyte
 Microgametocyte - light red
to pink chromatin, diffuse,
central , gives tint to light
blue cytoplasm; yellowish
brown pigment
 Macrogametocyte- small,
Gametocytes of P. vivax in thin
compact, dark red eccentric
blood smears.
chromatin, cytoplasm dark Fig. 28 and 29: Nearly mature and
blue, no vacuoles, abundant mature macrogametocyte
dark brown pigment (female);
scattered throughout the Fig. 30: Microgametocyte (male).
cytoplasm
Plasmodium vivax (benign
tertian)

Macrogametocytes of P. vivax in a thin blood smear.

Note the enlargement of the gametocytes compared to uninfected RBCs.
Plasmodium vivax (benign
tertian)

Macrogametocytes of P. vivax in thin blood smears.

Plasmodium ovale (benign
tertian
 Infected rbc
 Somewhat larger than normal, often with
fringed or irregular edge, and oval in shape

Ring-form trophozoites of P. ovale in thin blood smears. Fig. 1: Normal red

cell; Figs. 2-5: Ring-form trophozoites.
Plasmodium ovale (benign
tertian

Ring-form trophozoites of P. ovale in thick blood smears.

 Plasmodium ovale (benign
tertian

Note the multiply-infected RBC

Ring-form trophozoites of P. ovale in thin blood smears.

Plasmodium ovale (benign
tertian

Trophozoite of P. ovale in a thick blood smear.

Plasmodium ovale (benign
tertian)
 Schizont (presegmenting)
 About 25% of infected rbc are definitely oval
shaped; usual picture is that of a round
parasite in the center of an oval cell
 Many cells with indefinite fringed outline
Plasmodium ovale (benign
tertian)

Schizonts of P. ovale in thick blood smears.

Plasmodium ovale (benign
tertian)

Schizonts of P. ovale in thin blood smears.

Plasmodium ovale (benign
tertian)

Gametocyte of P ovale in a thick blood smear.

Gametocyte of P. ovale (red arrow) nestled between two white blood cells
in a thick blood smear.
 Plasmodium ovale (benign
tertian)
Microgametocyte Macrogametocyte

Microgametocyte of P. ovale in a thin blood smear. Note the elongated, oval

shape and the Schüffner's dots.
Macrogametocyte of P. ovale in a thin blood smear. Note the fimbriation.
Plasmodium ovale (benign
tertian)

Macrogametocytes of P. ovale in thin blood smears, showing Schüffner's

dots.
Plasmodium malariae
( quartan)
 Infected rbc
 Normal or slightly smaller
 Sometimes darker in early stages
 Multiple infection of rbc are rare
Plasmodium malariae
( quartan)

Ring-form (lower right) and

developing (upper left) "Birds-eye" trophozoite of P. malariae
trophozoites of P. malariae in a thin blood smear.
in a thick blood smear.
Plasmodium malariae
( quartan)

Ring-form trophozoites of P. malariae in thin blood smears

Plasmodium malariae
( quartan)

Developing trophozoites of P. malariae.

Figs. 6-13: Increasingly mature trophozoites;
Figs. 10 and 13 are "band forms."
Plasmodium malariae
( quartan)

Trophozoites of P. malariae in thick blood smears

Plasmodium malariae
( quartan)

Band-form trophozoites of P. malariae in a thin blood smear.

Plasmodium malariae
( quartan)

: Basket-form trophozoites of P. malariae in a thin blood smear.

 Plasmodium malariae
( quartan)

Schizonts of P. malariae have 6-12 (usually 8-10) merozoites, often arranged in a

rosette or irregular cluster. Mature schizonts nearly fill the normal-sized host
RBC. Pigment if course and often peripheral. Schizonts can be common in
peripheral blood circulation.
Plasmodium malariae
( quartan)

: Schizonts of P. malariae in thick blood smears.

Plasmodium malariae
( quartan)

Schizonts of P. malariae in thin blood smears.

Plasmodium malariae
( quartan)

Schizonts of P. malariae in thin blood smears.

Plasmodium malariae
( quartan)

Gametocytes of P. malariae in thin blood smears.

Plasmodium malariae
( quartan)

Developing gametocytes of P. malariae in thin blood smears.

Treatment and Management
 Antimalarial drugs have selected action on the different phases
of the life cycle of malaria:
 Causal prophylactic drugs – prevents the establishment of
parasite in the liver
 Blood schizonticidal drugs – which attack the parasite in the
rbc
 Tissue schizoticides – act on the pre-erythrocytic forms in the
liver
 Gametocidal drugs – destroy the sexual form of parasite in the
blood.
 Hypnozoiticidal or anti relapse drug – which kill the dormant
forms in the liver
 Sporonticidal drugs – inhibit the developmen of the oocyst on
the gut wall of the mosquito, which fed on a gametocyte carrier,
so that the mosquito cannot transmit an infection.
Main uses of anti-malarial drugs
:
1. Protective (prophylactic)
2. Curative (therapeutic
3. Preventive
Prophylaxis
 Used before the infection occurs or before it
become evident, with the aim of preventing
either the occurrence of the infection or any
of its symptoms.
Curative or therapeutic
 Refers to the action on the established
infection, which involves the use of blood
schizonticidal drugs for the treatment of the
acute attack and the case of relapsing
malaria, radical treatment of the dormant
liver forms.
Prevention
 Deterrence of infection in mosquitos with the
use of gametocytocidal drugs to attack the
gametocytes in the blood of the host.
 Chloroquine
 Sulfadoxine –pyrimethamine combination or
quinine
 Artemissin and its derivatives
 New antimalarial drugs
Epidemiology
 World’s most important
tropical parasitic disease
 IN the Philippines, there
is relatively high
endemicity in provinces of
Palawan, Kalinga
Apayao, Ifugao abd
Agusan del Sur.
 Multidrug resistant
falcifarum malaria –
Davao del Norte,
Compostella Valley, and
Palawan.
 70% of malaria in the Phil. – caused by
P.falcifarum less than 30% P. vivax
 P. malariae – 1%
 P. ovale – reproted in Palawan in 1960.
Vector

A.litoralis
Vector
 Anopheles minimus var, flavirostris – night biter,
which prefer to breed in slow flowing , partly shaded
streams that abound the foothill areas.
 Anopheles litoralis –associated with malarial
transmission in the coastal areas of Mindanao
(Sulu).
 Anopheles maculates – co-exist with A. flavirostris in
the portion streams exposed to sunlight.
 Anopheles mangyanus – has the same beeding
habitats and seasonal prevalence as A. flavirostris
but appears to prefer habitats located in forest
fringes.
 Can be transmitted through blood transfusion
from infected donors.
 Infected mothers transmit parasites to their
child before or during birth (Congenital
malaria).
Prevention and control
 Early diagnosis and prompt treatment of
malaria are essential for control.
 Epidemics should be detected early and
contained.
 Personal protection measures against
mosquito bites are also helpful such as
staying in a well-screened areas, using
mosquito nets tucked under the mattress and
preferably treated with permethrin or
deltamethrin.
 Wearing appropriate
clothing which cover most
of the body and which are
light colored (since dark
color attracts the
mosquitoes).
 Using insect repellant
containing DEET (
N,N-diethyl-m-
toluamide)on exposed
part of the body .
 Using flying insect spray
containing pyrrethrum in
living areas, and use of
permethrim insecticide as
a repellant spray for
clothing.
 Chemoprophylaxis may be
protective to travellers who
have no immunity to
malaria, although no
chemoprophylatic regimens
ensures 100% protection .
 Strategies implemented to
control malaria in
pregnancy include the use
of insecticide treated nets
(ITNs) and intermettent
preventive treatment.
 Work is going on for
development of an effective
malaria vaccine. Treatment of mosquito net by community
 Malaria control also 
includes proper vector
control.
 In the field of molecular
entomology, stable
germ line
transformation of the
 Applying expanded
Anopheles mosquito is polystyrene beads to control
being investigated. mosquito breeding.
Control program

Releasing larviv

orous fishes in a pond

Releasing larvivorous fishes in a pond Fogging

The end