MALARIA Dr.T.V.Rao, MD Professor of Microbiology
Ancient History of Malaria • Malaria parasites have been with us since the dawn of time. They probably originated in Africa (along with mankind), and fossils of mosquitoes up to 30 million years old, show that the malaria vector, the malaria mosquito, was present well before the earliest history.
Hippocrates and Malaria • Hippocrates, a physician born in ancient Greece, today regarded as the "Father of Medicine", was the first to describe the manifestations of the disease, and relate them to the time of year and to where the patients lived.
Malaria • Name is derived from Italian Mal’ aria or bad air Malaria continues to be most important cause of fever and morbidity in the Tropical world Malaria has been eradicated from Europe, Most of North America, USA South America Korea and Japan,
History – Events on Malaria • 1880 - Charles Louis Alphose Lavern discovered malarial parasite in wet mount • 1883 - Methylene blue stain - Marchafava • 1891 - Polychrome stain- Romanowsky • 1898 - Roland Ross - Life cycle of parasite transmission, wins Nobel Prize in 1902 • 1948 - Site of Exoerythrocytic development in Liver by Shortt and Garnham
Major Developments in 20th Century • 1955 - WHO starts world wide malaria eradication programme using DDT • 1970 – Mosquitos develop resistance to DDT Programme fails • 1976 – Trager and Jensen in vitro cultivation of parasite • 1948 - Site of E1948 - Site of Exoerythrocytic dev in Liver by Shortt and Garnham • xoerythrocytic dev in Liver by Shortt and Garnham
Nobel Prizes in Malaria • The discovery of this parasite in mosquitoes earned the British scientist Ronald Ross the Nobel Prize in Physiology or Medicine in 1902. In 1907, Alphonse Lavern received the Nobel prize for his findings that the parasite was present in human blood.
Introduction • Malaria is probably one of the oldest diseases known to mankind that has had profound impact on our history. • It is a huge social, economical and health problem, particularly in the tropical countries. • Malaria is a vector-borne infectious disease caused by single-celled protozoan parasites of the genus Plasmodium. • Malaria is transmitted from person to person by the bite of female mosquitoes.
What causes Malaria • Malaria is caused by a parasite called Plasmodium, which is transmitted via the bites of infected mosquitoes. In the human body, the parasites multiply in the liver, and then infect red blood cells. • Transmission of Malaria do not occur <160c and >330c • Do not occur > 2000 meters altitude.
Parasites Cause of Malaria • Malaria is caused by an infection by one of four single celled Plasmodia species, they are: falciparum, vivax,malariae, and ovale. The most dangerous of the four is.P.falciparum
Falciparum most Dangerous • Falciparum accounts for 90% of deaths due to malaria and vivax is the most widely spread species because it exists in both temperate and tropical climates (Encarta). The malaria life cycle is a complex system with both sexual and asexual aspects .
Why it is important in Medicine • Malaria remains the world's most devastating human parasitic infection. Malaria affects over 40% of the world's population. WHO, estimates that there are 350 - 500 million cases of malaria worldwide, of which 270 - 400 million are Falciparum malaria, the most severe form of the disease.
Malaria Kills more people than AIDS • Malaria kills in one year what AIDS kills in 15 years. For every death due to HIV/AIDS there are about 50 deaths due to malaria. To add to the problem is the increasing drug resistance to the established drug.
Etiology of Malaria • Four Species known to infect Man • 1 Plasmodium vivax – Benign Tertian, Tertian Malaria • 2 P.ovale - Ovale tertian Malaria • 3 P.malariae – Quartan malaria • 4 P.falciparum – Falciparum malaria or Malignant Tertian malaria.
Events in Humans start with Bite of Mosquito • Man – Intermediate host. • Mosquito – Definitive host – Sporozoites are infective forms • Present in the salivary gland of female anopheles mosquito • After bite of infected mosquito sporozoites are introduced into blood circulation.
Human cycle 1 Pre erythrocytic schizogony 2 Erythrocytic Schizogony 3 Gametogony 4 Exoerythrocytic schizogony
Pre erythrocytic cycle • Sprozoites undergo developemtnal phase in the liver cell • Sprozoites are elongated and spindle shaped become rounded inside the liver parenchyma • Multiple nuclear divisions develop to Schozonts • A Schizont contains 20,000 – 50,000 merozoites.
Period of Pre erythrocytic cycle • 1 P.vivax 8 days • 2 P.falciparum – 6 days • 3 P.malariae - 13 – 16 days, • 4 P.ovale 9 days On maturation Liver cells ruputure Liberate Merozoites into blood stream
Affinity of Parasite to Erythrocytes • P.vivax • P.malariaeInfectes only young or • P.ovale Old Erythocytes • P.falciparum Infects all age groups Also adhere to the endothelial lining of Blood vessesl Causes the obstruction, Thrombosis and Local Ischemias
Erythrocytic Schizogony • Liberated Merozoites penetrate RBC • Three stages occur 1 Trophozoites 2 Schizont 3 Merozoite
Erythrocytic cycle • Ruptured red cells release Merozoites which attack new red cells • Continue with Schizogony • Repeated cycles will continue • In P.falciparum - infected erythrocytes with Schizonts aggregate in the capillaries of brain and other internal organs • Only ring forms are seen in the blood smears
Trophozoites • After invasion grow and feed on hemoglobin • Blue cytoplasm and red nucleus, Called as Signet ring appearance • Hence called ring form
Schizont • When the Trophozoite is fully developed becomes compact. • Malarial pigments are scattered through the cytoplasm • The Nucleus is large and lies at the periphery starts dividing. • Becomes Schizont
Exo Erythrocytic Schizogony • Some Sprozoites do not undergo sporogony in the first instance • But go into resting stage called as Hypnozoites,( hibernation ) • Within 2 years reactivate to form Schizonts release Merozoites and attack red cell and produce relapses • Absent in P falciparum
Gametogony • Merozoites differentiate into Male and female gametocytes • Macrogametocytes also called female gametocytes • Microgametocyte also called as male gametocytes • They develop in the red cells • Found in the peripheral blood smears • Microgametocyte of all species are similar in size • Macro gametocytes are larger in size.
Mosquito cycleSexual cycle • Sexual cycle will be initiated in the Humans by the formation of Gametocytes • Develop further in the female Anopheles Mosquito • Only mature sexual forms are capable of further development in Mosquito • In midgut one Microgametocyte develops into 4-8 thread like filamentous structures named Micro gametes • From one macrogametocyte only one macrogamete is formed
Events in Mosquitos • Fertilization occurs when a Microgametocyte penetrate into Macrogametocyte • Fertilized macrogametocyte is known as ZYGOTE • ZYGOTE matures into OOKINETE • OOKINETE to OOCYST
Formation of Sporozoites in Mosquitos. • OOCYST matures with large number of Sporozoites ( A few hundred to thousands.) • OOCYST ruptures and release SPOROZOITES in the body cavity of Mosquito • There is a specific predilection for salivary glands • Now capable to transmit the infection to new Host
Pathology and Pathogenesis • Sporozoites result from sexaul and sporogenic cycle of development in mosquitoes and injected into human blood serum. • Events start with bite of Infected Anopheles Mosquitoes • Sporoozoites enter liver, in 1 hour infect the parenchymal cell.
Pathogenesis in Pre Erythrocyte cycle • Numerous asexual progeny – Merozoites ruputure and leave from liver cells • Enter the Blood and invade Erythrocytes • Erythrocytic cycle starts – Multiply in species specific fashion • Broods of Merozoites appearing at 48 hour interval in P.ovale, P.vivax , P.falciparum • P.malariae appear in 72 hour cycles,
Erythrocyte cycle • Merozoites released invade red cells • P.vivax infects young erythrocytes • P.malariae Infects old erythrocytes • P.falciparum infects RBC of all ages • The Merozoites are pear shaped 1-5 microns in length • The receptors for Merozoites are on red cells in the glycoprotein
Chooses to enter the RBC • Specific for each species • They pit on red cells • By endocytosis enters the RBC • Becomes a Trophozoites