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
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)
After a week, trophozoites are mature
At this point, trophozoites undergo schizogony
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
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, 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. 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
