Malaria

Malaria is fatal disease caused by a

parasite that commonly infects a certain
What
type ofis Malaria
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
Infected all stage of RBC
Maurers dots ( blue dots)
Cresent gametocyt
Trofozoit ring
form,multiple ring form
Skizon is rarely seen in
blood stream
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
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.
48 hours cycle
Infected reticulocytes
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 (three-day cycle). In
some chronically infected
patients P. malariae can cause
serious complications such as
the nephrotic syndrome.
Infected old RBC
No enlargement of RBC
No dots
Mature skizons contain 6 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.
Anopheles

mosquitoes
Malaria is transmitted among humans by female 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
Prevention
chloroquine , kina, hidroklorokuin, amodiakuin (only
destroy the parasites in blood not in liver )
Fansidar pirimetamin + sulfadoksin (chloroquin
resistance areas)
Radical Treatment
Primaquine or another aminokuinolon

In addition, primaquine is active against the dormant

parasite liver forms (hypnozoites) and prevents
relapses. Primaquine should not be taken by pregnant
women or by people who are deficient in G6PD (glucose-
6-phosphate dehydrogenase). Patients should not take
primaquine until a screening test has excluded G6PD
deficiency.
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 flu-
like illness while traveling, and up to 1 year after
returning home, should immediately seek
professional medical care.