Malaria

Malaria is fatal disease caused by a

parasite that commonly infects a certain
What
Malaria
type ofis
mosquito
which feeds on humans
Four kinds of malaria parasites have long
been known to infect humans: Plasmodium

falciparum, P. vivax, P. ovale, and P. malariae (P.

knowlesi, a type of malaria causing malaria that is
transmitted from animal to human ("zoonotic"
malaria).

Although malaria can be a deadly disease,

illness and death from malaria can usually
be prevented.

How is malaria transmitted?

Usually, people get malaria by being bitten by an

infective female Anopheles mosquito.
Only Anopheles mosquitoes can transmit malaria
and they must have been infected through a
previous blood meal taken from an infected
person.
Because the malaria parasite is found in red blood
cells of an infected person, malaria can also be
transmitted through :
- blood transfusion,
- organ transplant, or
- the shared use of needles or syringes contaminated
with blood.
- Malaria may also be transmitted from a mother to
her unborn infant before or during delivery
("congenital" malaria).

Malaria Parasites

Malaria parasites are micro-organisms that belong

to the genus Plasmodium.
There are more than 100 species of Plasmodium,
which can infect many animal species such as
reptiles, birds, and various mammals.
Four species of Plasmodium have long been
recognized to infect humans in nature

Plasmodium falciparum, P. vivax, P. ovale , and P.

malariae (P. knowlesi, a type of malaria causing
malaria that is transmitted from animal to
human ("zoonotic" malaria).

Plasmodium falciparum

which is found worldwide in tropical and

subtropical areas.
P. falciparum can cause severe malaria (severe
anemia,cerebralmalaria and black water fever ).
36 48 hours cycle ( malaria tertiana maligna )
Infected all stage of RBC parasitemia level
50 %
Maurers dots ( single blue dots bigger than
Schoefner dots)
Cresent gametocyt
Trofozoit ring form,multiple ring form
Skizon is rarely seen in blood stream, mature
skizon contained 18 24 merozoites

Plasmodium falciparum

Plasmodium vivax

which is found mostly in Asia, Latin America, and in some parts

of Africa.
P. vivax (as well as P. ovale) has dormant liver stages
("hypnozoites") ("relapse).
Enlargement of erythrocyte
48 hours cycle ( malaria tertiana benigna )
Parasitemia 2 5 %
Schuffner dots
Trophozoites are ameboid
Mature skizon contains 12 24 merozoites
Infected reticulocytes
All development stadiums are found in blood stream

Plasmodium vivax

Plasmodium ovale

P. ovale is found mostly in Africa (especially West

Africa) and the islands of the western Pacific.
It is biologically and morphologically very similar
to P. vivax
Hipnozoite form relaps but rare than P.vivax
48 hours cycle ( malaria tertiana)
Infected reticulocytes parasitemia level 2 5
%
The shape of infected RBC oval shape and
bigger
The ring form < P.vivax
Trophozoites less amoeboid
Mature skizon contains 8 merozoites

Plasmodium ovale

Plasmodium malariae

found worldwide, is the only human malaria

parasite species that has a quartan cycle (threeday cycle). In some chronically infected patients
P. malariae can cause serious complications such
as the nephrotic syndrome.
Incubation period longer than P.vivax and P ovale
periode ( 27 40 days)
Infected old RBC
No enlargement of RBC
No dots
Mature skizons contain 12 merozoites
(rossette)
Trofozoites band form

Plasmodium malariae

Plasmodium knowlesi

is found throughout
Southeast Asia as a natural
pathogen of long-tailed and
pig-tailed macaques.
It has recently been shown to
be a significant cause of
zoonotic malaria in that
region, particularly in
Malaysia.
P. knowlesi has a 24-hour
replication cycle and so can
rapidly progress from an
uncomplicated to a severe
infection; fatal cases have
been reported.

Malaria is transmitted among humans by female mosquitoes

Anopheles
mosquitoes
of the genus Anopheles.
There are approximately 3,500

species of mosquitoes grouped into 41 genera, only 30-40

species transmit malaria (i.e., are "vectors") in nature.
Female mosquitoes take blood meals to carry out egg
production, and such blood meals are the link between the
human and the mosquito hosts in the parasite life cycle.
The successful development of the malaria parasite in the
mosquito (from the "gametocyte" stage to the "sporozoite"
stage) depends on several factors.
The most important is ambient temperature and humidity
(higher temperatures accelerate the parasite growth in the
mosquito) and whether the Anopheles survives long enough to
allow the parasite to complete its cycle in the mosquito host
("sporogonic" or "extrinsic" cycle, duration 10 to 18 days).
Differently from the human host, the mosquito host does not
suffer noticeably from the presence of the parasites.

Life Cycle in Human

The natural ecology of malaria involves malaria parasites

infecting successively two types of hosts: humans and
female Anopheles mosquitoes.
In humans, the parasites grow and multiply first in the liver
cells and then in the red cells of the blood.
In the blood, successive broods of parasites grow inside the
red cells and destroy them, releasing daughter parasites
("merozoites") that continue the cycle by invading other red
cells.
The blood stage parasites are those that cause the
symptoms of malaria.
When certain forms of blood stage parasites
("gametocytes") are picked up by a female Anopheles
mosquito during a blood meal, they start another, different
cycle of growth and multiplication in the mosquito.

Life Cycle in Mosquito

After 10-18 days, the parasites are found (as
"sporozoites") in the mosquito's salivary glands.
When the Anopheles mosquito takes a blood meal on
another human, the sporozoites are injected with the
mosquito's saliva and start another human infection
when they parasitize the liver cells.
Thus the mosquito carries the disease from one human
to another (acting as a "vector").
Differently from the human host, the mosquito vector
does not suffer from the presence of the parasites.

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, in P. 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.

Pathogenesis

Infection with malaria parasites may result in a

wide variety of symptoms, ranging from absent or
very mild symptoms to severe disease and even
death. Malaria disease can be categorized as
uncomplicated or severe (complicated).
In general, malaria is a curable disease if
diagnosed and treated promptly and correctly.
All the clinical symptoms associated with malaria
are caused by the asexual erythrocytic or blood
stage parasites.

Pathogenesis

When the parasite develops in the erythrocyte,

numerous known and unknown waste substances
such as hemozoin pigment and other toxic factors
accumulate in the infected red blood cell.
These are dumped into the bloodstream when the
infected cells lyse and release invasive merozoites.
The hemozoin and other toxic factors such as
glucose phosphate isomerase (GPI) stimulate
macrophages and other cells to produce cytokines
and other soluble factors which act to produce
fever and rigors and probably influence other
severe pathophysiology associated with malaria.

Incubation Periode

The incubation period in most cases varies from 7 to 30

days. The shorter periods are observed most frequently
with P. falciparum and the longer ones with P. malariae.
Antimalarial drugs taken for prophylaxis by travelers can
delay the appearance of malaria symptoms by weeks or
months, long after the traveler has left the malaria-endemic
area.
Returned travelers should always remind their health-care
providers of any travel in areas where malaria occurs during
the past 12 months.
In P. vivax and P. ovale infections, patients having recovered
from the first episode of illness may suffer several
additional attacks ("relapses") after months or even years
without symptoms. Relapses occur because P. vivax and P.
ovale have dormant liver stage parasites ("hypnozoites") that
may reactivate.

Uncomplicated Malaria

The classical (but rarely observed) malaria attack lasts 6-10

hours. It consists of
1. a cold stage (sensation of cold, shivering)
2. a hot stage (fever, headaches, vomiting; seizures in young
children)
3. and finally a sweating stage (sweats, return to normal
temperature, tiredness).
Classically (but infrequently observed) the attacks occur
every second day with the "tertian" parasites ( P. falciparum,
P. vivax, and P. ovale) and every third day with the "quartan"
parasite (P. malariae).
More commonly, the patient presents with a combination of
the following symptoms:
Fever , Chills , Sweats , Headaches , Nausea and vomiting Body
aches , and General malaise

Severe Malaria

Cerebral malaria, with abnormal behavior, impairment of

consciousness, seizures, coma, or other neurologic abnormalities
Severe anemia due to hemolysis (destruction of the red blood cells)
Hemoglobinuria (hemoglobin in the urine) due to hemolysis
Acute respiratory distress syndrome (ARDS), an inflammatory
reaction in the lungs that inhibits oxygen exchange, which may
occur even after the parasite counts have decreased in response to
treatment
Abnormalities in blood coagulation
Low blood pressure caused by cardiovascular collapse
Acute kidney failure
Hyperparasitemia, where more than 5% of the red blood cells are
infected by malaria parasites
Metabolic acidosis (excessive acidity in the blood and tissue fluids),
often in association with hypoglycemia
Hypoglycemia (low blood glucose). Hypoglycemia may also occur in
pregnant women with uncomplicated malaria, or after treatment
with quinine.

Diagnosis

Microscopic Diagnosis
Malaria parasites can be identified by examining
under the microscope a drop of the patient's blood,
spread out as a "blood smear" on a microscope
slide. Prior to examination, the specimen is stained
(most often with the Giemsa stain) to give the
parasites a distinctive appearance. This technique
remains the gold standard for laboratory
confirmation of malaria. However, it depends on
the quality of the reagents, of the microscope, and
on the experience of the laboratorian.
Antigen Detection
Molecular Diagnosis
Serology
Drug Resistance Tests

Treatment
Treatment a patient with malaria depends on:

The type (species) of the infecting parasite

The area where the infection was acquired and its
drug-resistancestatus
The clinical status of the patient
Any accompanying illness or condition
Pregnancy
Drug allergies, or other medications taken by the
patient

Treatment
Artemisinin (Artemisinin Combination
Therapy/ ACT) sebagai terapi lini pertama
dalam penanganan malaria tanpa komplikasi
di daerah yang telah dikonfirmasi multidrug
resistance untuk mencegah kegagalan terapi,
resistensi dan relaps.
Penggunaan ACT merupakan kombinasi dari
dua atau lebih obat anti malaria
Saat ini terdapat dua regimen ACT yang
digunakan dalam program malaria yaitu artesunat
amodiakuin (AAQ) dan dihidroartemisinin pip
erakuin (DHP).

Prevention

Keeping mosquitoes from biting you, especially at

night
Taking antimalarial drugs to kill the parasites
Spraying insecticides on your home's walls to kill
adult mosquitoes that come inside
Sleeping under bed netsespecially effective if
they have been treated with insecticide, and
Using insect repellent and wearing long-sleeved
clothing if out of doors at night.
Any traveler who becomes ill with a fever or flulike illness while traveling, and up to 1 year after
returning home, should immediately seek
professional medical care.

P. FALCIPARUM
Parasit

ini menyerang eritrosit tua dan

muda
Manifestasi klinis : hiperparasitemia,
anemia, malaria serebral, ikterus,
splenomegali, gagal ginjal dan koma
Siklus : 36- 48jam

P.Falciparum
Trofozoit

Ciri morfologis
Inti

berwarna merah,
protoplasma bentuk
cincin atau seperti
garis biru pada tepi
eritrosit,
SDM tidak membesar
Bentuk cincin halus
dan kecil
Sering ada double dots
( 2 inti)

Morfologi
Makrogametosit (betina)

Ciri morfologis
Bentuk

khas seperti
pisang (banana form),
tampak pigmen coklat
tua di sekitar inti
Makrogametosit
berbentuk pisang
langsing, inti padat,
dikelilingi pigmen,
sitoplasma berwarna
biru:

Morfologi
Mikrogametosit(jantan)

Ciri morfologis
Mikrogametosit

berbentuk pisang,
agak gemuk,
ujungmya tumpul,
inti dikelilingi pigmen,
sitoplasma berwarna
merah pucat.

PLASMODIUM VIVAX
Cenderung

menginfeksi sel eritrosit yang muda

Sel eritrosit yang terinfeksi berukuran lebih besar
daripada eritrosit normal
Siklus 48 jam
Terdapat titik Schuffner setelah 8 10 jam
Gejala klinis : demam, menggigil, anemia,
splenomegali
Perjalanan penyakit relaps ( stadium hipnozoit
didalam hepar )

Morfologi P.vivax
Trofozoit

Ciri morfologis
Cincin

berukuran

1/3 sel
bentuknya tidak
teratur ( amoeboid )
Tampak Vakoula,
inti lebih besar

Morfologi
schizon

Ciri morfologis
Protoplasma

padat

( inti sudah
terbagi ) menjadi
merozoit
Merozoit berjumlah
12-24 buah

Morfologi
Gametosit

Ciri morfologis
Mengisi

seluruh

eritrosit,
Sitoplasma
homogen
Pigmen halus dan
difus

PLASMODIUM OVALE
Cenderung

menginfeksi sel eritrosit yang

muda
Sel eritrosit yang terinfeksi berukuran lebih
besar daripada eritrosit normal dan
berumbai (oval)
Siklus 48 jam
Terdapat titik Schuffner pada fase awal
infeksi
Perjalanan penyakit relaps ( stadium
hipnozoit didalam hepar ) namun jarang
Gejala klinis lebih ringan dari P.vivax

Morfologi P.ovale
Trofozoit

Ciri morfologis
Satu kromatin dot,

berbentuk cincin, inti

padat
Trofosoit dewasa
mempunyai pigmen
kasar
SDM berbentuk oval
dan berfimbriae

Morfologi
schizon

Ciri morfologis
Lebih

kecil dari
P.vivax
Jumlah merozoit
biasanya 8 buah
Masa kromatin
sedikit, pigmen
kasar

Morfologi
gametosit

Ciri morfologis
Bentuk

oval dengan
tepi berumbai
Sitoplasma
homogen
Pigmen difus
berwarna coklat
meliputi parasit

PLASMODIUM MALARIAE
Cenderung

menginfeksi sel eritrosit

yang tua
Sel eritrosit yang terinfeksi berukuran
normal
Siklus 72 jam
Tidak terdapat titik titik yang khas

Morfologi
Trofozoit

Ciri morfologis
Berbentuk

cincin
dan pita atau band
form
Pigmen kasar dan
berwarna coklat tua

Morfologi
schizon

Ciri morfologis
Plasma

dalam inti
sudah terbagi
Merozoit berjumlah 8-12
buah
Pigmen-pigmen kasar
berkumpul di tengah
dikelilingi oleh merozoit
yang letaknya teratur
disebut rosette

Morfologi
gametosit

Ciri morfologis
Sitoplasma

menjadi

homogen
dikelilingi pigmen
kasar berwarna
coklat