Malaria

thy cunning seeds, Oh, million-

murdering Death.
-Ronald Ross
 Malaria
From the Italian mal aria - Bad Air
Also known as ague, marsh disease
Descriptions of malaria go as far back as
3550 B.C.
Caused by species of the genus
Plasmodium.
There are nine sub-genera.
Three occur in mammals
Four occur in birds
Two occur in lizards
 Taxonomy

Kingdom: Animalia
Phylum: Apicomplexa
Class: Coccidia
Order: Haemosporidia
Genus: Plasmodium
Species: vivax, falciparum, ovale &
malariae
 Parasitic Human Malarias
Of the nine sub-genera, there are four
that are typically parasitic to humans
P. falciparum
P. vivax
P. malariae
P. ovale
Each is more closely related to other Plasmodium
lineages than each other
 Hosts of Plasmodium

Plasmodium requires two types of

host
Vertebrate and Invertebrate
Definitive host is the invertebrate
(Anopheles spp.)
Sexual reproduction occurs
Intermediate host is the vertebrate
(Humans)
Asexual reproduction occurs
 Reproduction and
maturation in definitive
host
Anopheles spp. ingest erythrocytes containing
Plasmodium gametocytes
If an unsuitable species of mosquito ingests Plasmodium
gametocytes, they are digested
Macrogametocytes and Microgametocytes are
released from erythrocytes
Macrogametocyte matures into macrogamete (Nucleus shift)
Microgametocyte matures into microgamete (exflagellation)
Microgametes fertilize macrogametes
Diploid zygote becomes a motile ookinete
Reproduction and maturation in
definitive host, contd

The motile ookinete penetrates the stomach lining of

the mosquito
Once there, the ookinete begins to form an oocyst
Sporoblasts begin to form within the oocyst
Sporoblasts divide repeatedly to form sporozoites
Sporozoites break out of the oocyst and migrate
throughout the body of the mosquito
This entire process (from ookinete to sporozite) can take from
10-21 days
Some sporozoites end up in the salivary gland of
Anopheles, where they are transmitted when the
mosquito takes a blood meal
Life cycle illustration
Reproduction and maturation
in the intermediate host
Sporozoites injected by Anopheles
migrate to liver from the bloodstream
Covered in a protein that aids in access to
hepatocytes
Entry into hepatocytes is the beginning
of the pre-erythrocytic cycle
Upon entry into hepatocytes, sporozoites
become feeding trophozoites
Some sporozoites go dormant indefinitely
(depending on Plasmodium spp) QuickTime and a
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After a week, trophozoites are mature

At this point, trophozoites undergo schizogony
 Reproduction and maturation
in the intermediate host, contd
Merozoites re-enter the blood from the liver and
penetrate red blood cells
Upon entry, merozoites become trophozoites again
At this stage, trophozoites display distinctive
signet-ring appearance, feed on hemoglobin Quic kTime and a
TIFF (Unc ompres s ed) dec ompres s or

After maturing in the RBC, trophozoites again form a are needed to s ee this pic ture .

schizont, creating more merozoites

RBC ruptures, releasing merozoites, and parasite
metabolic wastes, which causes many of the
symptoms of malaria
One of these, hemozoin, a byproduct of parasitic
consumption of hemoglobin, is toxic, and causes
inhibition of macrophages
After a number of generations, some merozoites
become macro and microgametocytes
Ingestion of gametes causes infection in
Anopheles
If not ingested, gametes are phagocytized
Human cycle
 P. falciparum
Is the most dangerous of the malaria parasites
Accounts for 50 % of all malaria cases
Causes malignant tertian malaria
Symptoms appear 9 to 14 days after initial infection
Parasitemia levels are extremely high
Up to 65% of erythrocytes infected
Schizonts grow in liver cells
Schizont ruptures in 5 1/2 days, releasing 30,000
merozoites
Schizonts are more asymmetrical than other Plasmodium
spp.
Infected RBCs can attach to uninfected RBCs, forming rosettes
Rosettes can clog venules
Falciparum trophozoites secrete proteins that cause
deformations of erythrocytes
Falciparum trophozoites extend pseudopodia, but are not as
active as P.vivax trophozoites
Falciparum gametocytes are crescent shaped
 P.vivax
Trophozoites of P.vivax are much more motile than other
plasmodium spp.
This motility caused Italian researchers to nickname it vivace,
Italian for quick and lively
P.vivax flourishes in temperate zones
Most cases of P.vivax malaria now occur in Asia
P.vivax is common in North Africa, but not in tropical Africa
Africans have a natural resistance to this form of malaria
Schizonts are formed in the liver parenchyma and release 10,000
merozoites upon maturation
Trophozoites cannot penetrate mature red cells
In addition, merozoites can only penetrate RBCs with mediated
receptor sites
Receptor sites are genetically determined, conferring
resistance
A defining characteristic of P.vivax is the development of
hypnozoites
Hypnozoites cause relapse of malarial infection
 P.vivax, contd
P.vivax gametocytes are rounded
It appears that P.vivax gametocytes do not require
several generations to appear
Causes benign tertian malaria
Symptoms appear between 12 and 18 days after
initial infection
 P. Malariae
Causes quartan malaria
Causes paroxysms every 72 hours
Is cosmopolitan, but does not have continuous
distribution
Is found in many regions of tropical Africa, Asia,
South America, and even Europe
Is thought to be the only Plasmodium organism
that lives in wild animals
Parasitemia levels are low
One parasite per 20,000 red cells
Symptoms appear between 18 and 40 days
after initial infection
 P. Ovale
Rarest of the four malaria parasites
Causes tertian malaria
Symptoms appear between 12 and 18 days after initial
infection
Common to western coastal Africa, also found in India,
the Philippines, New Guinea, and Vietnam
Difficult to diagnose due to its similarity to P.vivax
Gametocytes take longer to appear in blood than those
of other species
 Symptoms
Common symptoms
Fever
Chills
Headache
Sweats
Fatigue
Nausea and vomiting
P.falciparum
Causes Cerebral Malaria, which accounts for 10 % of hospital admitted
malaria cases and 80%
Mild jaundince
Enlarged liver
Increased respiratory rate
Pulmonary edema
P.vivax
P.ovale
P.malariae
 Pathogenesis
Clinical signs of malaria can be attributed
to two factors
Host inflammatory response
Produces chills and fever
Correlated with maturation of merozoites, rupture
of RBCs
Toxins released from burst RBCs can stimulate
secretion of TNF by macrophages
TNF overproduction and toxicity can cause most or
all of malaria symptoms
Anemia
Caused by destruction of RBCs
Control
 Diagnosis
Diagnosis of malaria can be difficult, because
many symptoms are general
Demonstration of the parasites in peripheral
blood is important to a diagnosis
Individuals with very low parasitemias can
often be overlooked
Several effective methods for diagnosis have
been developed
Fluorescent dye staining
DNA probe specific for P.falciparum
PCR diagnostics
ELISA detection of P.falciparum antigen
 Treatment
Treatment of malaria focuses on eradication of the
blood parasites
Several drugs can be administered, such as
Chloroquine
Quinine
Doxycycline
Malarone
Lariam
Fansidar
Treatment is dependent on several factors, including:
Type of malaria
Drug-resistance
Nearly all strains of P.falciparum are now chloroquine
resistant, in addition to developing resistance to nearly all
other currently available antimalarial drugs
P.vivax has also developed resistance to chloroquine and
primaquine, though they are not as widespread as
P.falciparum
 Impact of malaria
According to the WHO - World Malaria Report 2005:
At the end of 2004, some 3.2 billion people lived in areas
at risk of malaria transmission in 107 countries and
territories.
Between 350 and 500 million clinical episodes of malaria
occur every year.
At least one million deaths occur every year due to
malaria.
About 60% of the cases of malaria worldwide and more
than 80% of the malaria deaths worldwide occur in Africa
south of the Sahara.
In 1995, 990,000 deaths reported in some African countries where
malaria infection is high (2,700 deaths per day)
In 2000, 84% of the blood transfusion given in Kinshasa, Congo
were for anemia caused by malaria