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……thy cunning seeds, Oh, million-thy cunning seeds, Oh, million-murdering Death.murdering Death.
……thy cunning seeds, Oh, million-thy cunning seeds, Oh, million-murdering Death.murdering Death.
Malaria…Malaria…Malaria…Malaria…
--Ronald RossRonald Ross
MalariaMalariaMalariaMalaria 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
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
TaxonomyTaxonomy
Kingdom: Animalia Phylum: Apicomplexa Class: Coccidia Order: Haemosporidia Genus: Plasmodium Species: vivax, falciparum, ovale &
malariae
Kingdom: Animalia Phylum: Apicomplexa Class: Coccidia Order: Haemosporidia Genus: Plasmodium Species: vivax, falciparum, ovale &
malariae
Parasitic Human MalariasParasitic 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
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 PlasmodiumHosts 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
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
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
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, cont’d
Reproduction and maturation in definitive host, cont’d
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
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 illustrationLife cycle illustration
Reproduction and maturation in the intermediate host
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) After a week, trophozoites are mature
At this point, trophozoites undergo schizogony
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) After a week, trophozoites are mature
At this point, trophozoites undergo schizogony
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Reproduction and maturation in the intermediate host,
cont’d
Reproduction and maturation in the intermediate host,
cont’d 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
After maturing in the RBC, trophozoites again form a 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
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
After maturing in the RBC, trophozoites again form a 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
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Human cycleHuman cycle
P. falciparumP. 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
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.vivaxP.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
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, cont’dP.vivax, cont’d
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.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. MalariaeP. 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
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. OvaleP. 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
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
SymptomsSymptoms 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
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
PathogenesisPathogenesis
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
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
ControlControl
DiagnosisDiagnosis 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
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
TreatmentTreatment 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
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 malariaImpact 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
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