Malaria What is malaria n Name means bad

Malaria

What is malaria? n Name means “bad air”- n Malaria is a serious and sometimes fatal disease caused by a parasite. Patients with malaria typically are very sick with high fevers, shaking chills, and flulike illness.

History n One of the oldest known diseases- 50, 000 years. n n n First advances in malaria were made in 1880 by a French army doctor named Charles Laveran. He looked into infected red blood cells and discovered the parasite was a protist. This was the first time a protist was discovered to cause a disease. Alphonse Laveran

History n n n Ronald Ross discovered that mosquitoes transmitted malaria in 1898. First effective medicine was discovered by Pierre Pelletier and Joseph Caventou. This medicine is called quinine, which comes from the bark of cinchona trees in Peru. No effective vaccine: only immunity is a result of multiple infections. Sir Ronald Ross

AGENT n n Malaria is caused by species of Plasmodium. The genus Plasmodium contains 172 species n only four species are known to infect humans. n n n Plasmodium falciparum Plasmodium malariae Plasmodium ovale Plasmodium vivax Plasmodium parasites are highly specific with female Anopheles mosquitoes

Salient features n n n Plasmodium species belong to phylum Apicomplexa. Resistant stage called spore is present. Hence also called Sporozoa. They live intracellularly at least during part of their life cycle. Alteration of generations: sexual phase and asexual phase. Alteration of hosts: Definitive host and intermediate host.

Types of Malaria n Falciparum: Almost 80% of cases and 90% of malaria deaths. Primarily found in South America and Africa. n Ovale: Rarest form. Found in West Africa. n Malariae: Found in Africa and SE Asia: Can infect other mammals n Vivax: 20% of infections. Widest geographic distribution.

Malaria Transmission n n Transmitted from one person to another by the bite of a female anopheles mosquito. The female mosquito bites during dusk and dawn and needs a blood meal to feed her eggs. Male mosquitoes do not transmit malaria as they feed on plant juices and not blood. About 380 species of anopheles mosquito, but only 60 are able to transmit malaria.

Life cycle n Parasite completes its life cycle in two hosts– MAN & MOSQUITO n n The asexual cycle occurs in MAN (Intermediate host) The sexual cycle occurs in MOSQUITO (definitive host) Exo – erythrocytic stage ASEXUAL CYCLE (Schizogony) SEXUAL CYCLE (Gametogony) Erythrocytic stage

Exo-erythrocytic cycle n Developmental stage in the liver cells. n The sporozoites enter the hepatocytes through the Kupffer cells with the help of the apical complex. n Within the hepatocytes, the parasites undergo multiple rounds of nuclear division without cytoplasmic division followed by budding or segmentation to form progeny called MEROZOITES.

Exo-erythrocytic cycle n The merozoites are released into the circulatory system followed by the rupture of hepatocytes. n The number of merozoites differ from spp to spp n Neither clinical manifestations nor any pathological changes are seen during this stage.

Persistence of malaria n Persistence of dormant asexual parasitic forms seen in some spp (P. vivax & P. ovale) – HYPNOZOITES CAUSES FOR PERSISTANCE: 2 theories put forward 1. Cyclic Theory 2. Hypnozoite Theory n n Once the host immunity fails these hypnozoites can reactivate & undergo schizogony at a later time resulting in Relapse & Recrudescence In P. falciparum there is no relapse as all the intrahepatic schizonts rupture almost simultaneously.

Hepatic Schizont

Erythrocytic cycle n n Merozoites released from the hepatocytes invade the RBC The merozoites recognize specific proteins on the surface of the RBC & actively invade the cell. After entering the RBC the parasite undergoes a trophic period followed by an asexual replication.

Erythrocytic cycle contd… § After the parasite enters the RBC, it grows rapidly utilizing host nutrients. § As it grows, the parasite takes on different shapes & sizes. The nucleus then divides into several portions to form multinucleated Schizont

Erythrocytic cycle contd… n n 1. 2. 3. The RBC becomes more spherical and finally ruptures releasing newly formed merozoites into the blood stream. These merozoites have 3 fates: They invade fresh RBC to initiate a new erythrocytic cycle. They die due to inactivation by Igs or by phagocytosis. After a few erythrocytic cycle, some merozoites develop into sexual forms – male and female gametocytes.

Erythrocytic cycle contd… n n The duration of Erythrocytic cycle is constant for each spp of malarial parasite. P. falciparum – 48 hrs P. vivax - 48 hrs P. ovale - 48 hrs P. malariae - 72 hrs The newly formed merozoites do not invade the liver cells again.

Gametogony n n n As an alternative to schizogony some of the merozoites develop into sexual forms – male & female gametocytes The immature gametocytes develop in the blood vessels of spleen, bone marrow & enter the blood after attaining maturity (4 days) P. vivax gametocytes grow in the peripheral blood unlike P. falciparum, which grow in capillaries of internal organs and thus are found in circulation before they are completely developed.

Gametogony n n n Gametocytes do not cause any clinical symptoms They disappear from the circulation if not taken up by appropriate vector. The individuals who harbor the gametocytes are known as CARRIERS

Gametocyte - Plasmodium falciparum: The gametocytes of P. falciparum have a crescent or banana shape Gametocyte - Plasmodium malariae: The gametocytes of P. malariae have a round shape about the size of red blood cells. They have a fine granular appearance Gametocyte - Plasmodium ovale: A round gametocyte that is larger than normal red blood cells. It has a granular appearance as well as Schuffner's dots

Sexual life cycle n Occurs in the Definitive host – the Female Anopheles mosquito. n n When a female anopheles mosquito bites an infected host, both asexual & sexual forms enter. In the stomach of the mosquito, the asexual forms are destroyed but the gametocytes survive & undergo further development.

n n The microgametocyte undergoes 3 rounds of nuclear replication to form 8 nuclei which then becomes associated with flagella that emerge from the body of microgametocyte. This process is called as EX-FLAGELLATION. And the micro gametocytes are matured into micro-gametes.

§ The female gametocyte undergoes reduction division to get converted into single MACROGAMETE. § By chemotaxis, the highly motile microgamete fertilizes the macrogamete to form the ZYGOTE. § The zygote then lengthens first to a banana-shaped form & later matures into vermiform OOKINETE , which is motile and invasive.

n n The ookinite matures to form oocyst Oocyst later develops to form sporocyst which contains large number of sporozoites. Sporozoites have predilection for salivary glands, hence migrate to get concentrated in salivary glands of mosquito. These sporozoites during a blood meal are injected into a new host

Comparative Features of Plasmodium spp: Duration of asexual phase P. vivax P. falciparum P. malariae P. ovale 48 hrs 72 hrs 48 hrs Duration of sporogony in mosquito 10 – 12 days 10 days at 25 25 – 28 days at 27˚C - 30˚C at 22 - 27˚C Forms found in blood smear Ring forms & Trophozoites, gametocytes schizonts & gametocytes Trophozoites – Ring forms Cytoplasm opp the nucleus is thicker Cytoplasm fine & regular in outline. Often with 2 nuclei. Form vacuole. Same as P. vivax 14 days at 27˚C Same as P. vivax

P. vivax P. ovale • Assumes a compact form. • Pigment collects into a single mass. • Band like. • Slightly amoeboid • Vacuole disappears early • No ribbon shape. • Slightly amoeboid. Schizonts Regular, (Mature) almost completely fills an enlarged RBC Fills two-thirds of a red cell which is not enlarged. Regular , almost fills a normal sized red blood cell. Fills about threequarters of a red blood cell , which is enlarged. Merozoite Arranged in s an irregular grape like cluster Arranged in a grape like cluster Arranged Irregularly around a arranged. central mass of pigment like a “daisy” or a ”rosette” Growing forms • Irregular with vacuole. • Actively amoeboid. P. falciparum P. malariae

P. vivax P. falciparu m Dark brown or blackish; one or two solid blocks Malarial pigments Yellowish brown; fine granules Infected RBC’s Enlarged pale Crenated, Schuffner’s reddish violet dots present color and Maurer’s dots Gametocytes Spherical or globular. Much larger than a RBC. Host cell enlarged with Schuffner’s Crescenteric. Larger than a RBC. Host cell hardly recognizable P. malariae P. ovale Dark brown. Coarse granules Dark yellowish brown. Coarser than P. vivax Not much change. Zeimann’s dots on prolonged staining Slightly enlarged, oval shape, fimbriated. James’s dots appear early Round or oval. Size of a RBC. Host cell not enlarged. Oval. Size of a RBC. Host cell slightly enlarged with James’s dots

1. Malaria is transmitted to humans by the Anopheles mosquito, which injects the _______ stage of the organism Plasmodium. A) Oocyst B) Gametocyte C) Schizont D) Merozoite E) Sporozoite

2. Arrange the following in the proper order in which they occur during the human-phase of the Plasmodium life cycle. 1. Formation of schizont 2. Invasion of the liver 3. Invasion of red blood cells A)1, 2, 3 B)2, 1, 3 C)2, 3, 1 D)3, 2, 1 E)3, 1, 23.

3. Arrange the following in the proper order in which they occur during the mosquito-phase of the Plasmodium life cycle. 1. Formation of zygote 2. Formation of oocyst 3. Formation of sporozoites A)1, 2, 3 B)2, 1, 3 C)2, 3, 1 D)3, 2, 1 E)3, 1, 2

4. Plasmodium gametocytes are capable of producing gametes in mosquitoes, but not in human hosts. A) True B) False

5. The liver cells of people infected with malaria contain the ring trophozoite form of Plasmodium A) True B) False