Malaria… …thy cunning seeds, Oh, million-murdering Death
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Malaria… 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 hostVertebrate 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 gametocytesIf an unsuitable species of mosquito ingests Plasmodium gametocytes, they are digested 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 P.vivax gametocytes are roundedIt 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 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 Dostları ilə paylaş:
