PLASMODIUM

Classification
Phylum: Protozoa
Class: Sporozoa
Genus: Plasmodium
Species: vivax

History of Plasmodium

· Plasmodium is a protozoan parasite that is the causative agent of malaria in man.
· Plasmodium was discovered by Charles Louis Alphonse Laveran in 1880 AD in the Red Blood Corpuscles of the man suffering from malaria.
· Ronald Ross discovered the oocyte stage of malarial parasite in the tissue of female Anopheles mosquito.
· Giovanni Grassi and Amigo Bignami described the life cycle of parasites in female Anopheles mosquitoes.
· H.C. Schott and P.C. Garnham discovered the exo-erythrocytic cycle of Plasmodium.
· Endoparasite, found in the blood of man.
· Intracellular in RBCs and parenchymal cells of the liver.
· Also found in the alimentary canal and salivary glands of female Anopheles mosquito.
· There are 4 main species of Plasmodium. They are:

P. vivax, P. falciparum, P. malariae and P. ovale.

Parasite name	Type of malaria	Incubation period	Granules
P. vivax	Benign Tertian Malaria	14 days	Schaffner's dots
P. falciparum	Malignant Tertian Malaria or Cerebral Malaria or Black Water Fever or Subtertian Malaria	12 days	Maurer's dots
P. malariae	Benign Quartan Malaria	28 days	Ziemann's dots
P. ovale	Benign Tertian Malaria	14 days	Jame's dots or Schaffner's dots

Life Cycle of Plasmodium

· Life cycle of Plasmodium is completed in two hosts i.e. digenetic.

i) Primary or Principal host or Definitive Host– Mosquito (Based on Life Cycle or Biology)
ii) Secondary or Intermediate host– Man (Based on Life Cycle or Biology)

Also,
i) Primary or Principal host or Definitive Host– Man (Based on Disease or Medically)
ii) Secondary or Intermediate host– Mosquito (Based on Disease or Medically)

· Asexual cycle is completed in the human body (Liver & RBCs) and the sexual cycle is completed in the Stomach of the female Anopheles mosquito.

· Its life cycle can be divided into 3 phases.
i) Asexual Schizogony (occurs in the human body in Liver & RBCs)
ii) Sexual Gametogony (occurs in female anopheles mosquito)
iii) Asexual Sporogony (occurs in female anopheles mosquito)

· Plasmodium enters a man when infected female Anopheles mosquito bites and injects sporozoites into the blood of a human.
· Sporozoite is the infective stage to man.
· Sporozoites escape through the capillaries and penetrate into liver cells by lytic action of the secretion of their secretory organelles.

1. Asexual schizogony
· Schizogony is the asexual phase of reproduction that completes in the human body.
· Schizogony is a type of multiple fissions.

· It can be studied into following phases:

i) Pre-erythrocytic Schizogony
· Sporozoites grow to form a large and round Schizont in Liver cells.
· Schizont divides by multiple fission to form several spindle-shaped Merozoites.
· Rupture of schizont causes the release of Merozoites in the circulation and they are also called cryptozoites.
· Cryptozoites are immune to the natural resistance of the host as well as to medicines.

Pre and exo-erythrocytic schizogony

Sporozoites → Schizont → Multiple fission → Cryptomerozoites.

ii) Exo-erythrocytic schizogony
· These cryptozoites again re-enter into the liver cells and grow into schizonts. Schizonts again divide into merozoites, the merozoites thus produced are called metacryptozoites.

Cryptomerozoites → Schizont → Multiple fission → Mtacryptomerozoites.

· Metacryptozoites are of two types:

A. Micro-metacryptozoites and

B. Macro-metacryptozoites.

Micrometacryptozoites enter the RBCs and start the Erythrocytic cycle and Macrometacryptozoites attack fresh liver cells and begin Exo-erythrocytic schizogony again.

Exo-erythrocytic schizogony
· Exo-erythrocytic cycle is absent in P. falciparum.

· Pre-patent period: It is the duration between the initial sporozoite infection and the first appearance of the parasites in the blood.

· Incubation period: It is the duration between initial sporozoite infection and the first appearance of the symptoms in the body.

iii) Erythrocytic schizogony
· Each merozoite enters RBC, becomes round and grows at the expense of haemoglobin of RBC and is now known as a trophozoite.
· Trophozoites consume erythrocytes, grow in size and soon a vacuole is formed in the cytoplasm which pushes the nucleus to one side. This ring-shaped trophozoite is known as the signet-ring stage.
· As a result of further growth vacuole disappears and pseudopodia extend and ingest the cytoplasm, and break Haemoglobin down into Haematin and Globin.

· Globin (protein) is used for food by trophozoite and Haematin (Fe) forms a toxic malarial pigment called Haemozoin which brings about periodic fever in malaria patients.

· In certain species cytoplasm of trophozoites contain orange or yellow particles known as Schuffner’s dots.

Erythrocytic schizogony

· The trophozoite after this stage is ready for reproduction and is called Schizont.
· The nucleus of schizont divides by multiple fission, the haemozoin granules at the centre of the schizont and some protoplasm encircling each nucleus gives the schizont petal of rose flower-like structure i.e. Rosette stage.
· Release of Haemozoin into the blood causes fever.
· Incubation period is the duration between the initial sporozoite infection and the first appearance of malarial symptoms.
· Thus the schizont undergoes multiple fission to form merozoites called Micromerozoites.

Micrometacryptomerozoites → Trophozoites → Signet-ring stage → Amoeboid stage → Schizont → Rosette stage → Merozoites.

iv) Post-erythrocytic schizogony
· Micromerozoites produced in erythrocytic schizogony may enter into new liver cells to increase the number of merozoites rapidly.

2. Sexual Life cycle of Plasmodium
· Gametocytes of the malarial parasite are developed from merozoites in the RBCs of man.
· Sexual phase in the life cycle of Plasmodium occurs in the gut of the mosquito.
· Merozoites divide rapidly into two types of gametocytes e.g. Macrogametocytes and Microgametocytes.

· Gametocytes appear in the peripheral blood of man and when the female Anopheles mosquito bites the infected person again gametocytes enter into the alimentary canal of the mosquito.
· Microgametocytes are regarded as male gametes with a large central nucleus and clear cytoplasm.
· The process of forming whip-like sperms or Microgamates is known as ex-flagellation.
· The Macrogametocytes regarded as the Female nucleus, which is round with a small eccentric nucleus and large food-laden cytoplasm.
· The Macrogametocytes show very little change and they become mature Macrogametes or ova.

The sexual Life cycle of Plasmodium

Fertilization

· Microgamate attaches itself to the macrogamete and fuses to form a round zygote which is called Anisogamy (fusion of two dissimilar gametes).
· The zygote nucleus of Plasmodium is motile.
· The zygote remains inactive for sometimes but eventually it puts out a clear cytoplasm and it becomes long, vermiform and motile known as Ookinete.
· Ookinete penetrates the stomach wall of mosquitoes and comes to lie in sub-epithelial tissue which is enclosed by a cyst derived partly from the zygote and partly from the stomach tissue known as Oocyst or Sporont.

3. Asexual sporogony
· The Oocyst now grows about five times by absorbing nourishment, the nucleus of which divides many times and the cytoplasm develops vacuole which is called Sporoblast.
· Sporozoites are developed into the zygote. These sporozoites through the outer surface of the stomach reach into the Haemocoel of mosquitoes and swim to find their way into the salivary gland.
· Sporozoites are transmitted along with the saliva of mosquitoes when it bites a man.
· Pre and exo-erythrocytic phase of Plasmodium remains immune to the resistance of host and Antimicrobial drug.
· During the course of the disease spleen gets enlarged and it secretes Lysolecithin.

Malaria

The causative agent of malaria is Plasmodium vivax and its vector is the female (♀) Anopheles mosquito.

Symptoms of malaria
· Symptoms of malaria appear after the incubation period. This time is used by the parasites to increase their number. For malarial symptoms, a large number of parasites must continue the erythrocytic cycle at a time.

Malarial fever shows the following three successive stages.
a. Cold stage: At the onset of malarial fever, the patient suffers from a severe shaking chill. The patient feels so cold that his teeth chatter though he may be covered with a huge pile of blankets. The cold stage lasts for 20 minutes to 1 hour.

b. Hot stage: After the cold stage, the temperature of the body rises up to 41°C or 106 F. The patient feels very hot with a terrible headache. It lasts for 1-4 hours.

c. Sweating stage: When the temperature lowers down, the patient sweats profusely. Finally, fever comes down, temperature becomes normal and the patient feels comfortable till the next attack that occurs after 48 hours in case of vivax malaria.

· Malarial fever is due to malarial pigment haemozoin. This occurs when schizonts in RBCs burst and set free their contained merozoites and haemozoin in plasma.

Toxic haemozoin induces high fever and shivering.

Control of Malaria

Mosquito control

A. Physical control
· Using Door nets, Nets, Gauze etc.
· By the elimination of breeding grounds.
· Management of proper water drainage system.
· Use of petroleum substances and oil on water surfaces.

B. Chemical control
· By spraying insecticides like DDT, BHC etc

.
C. Biological control
· Using antilarval parasites like Bacillus thuringenesis, rearing Gambusia fish.

(Gambusia fish feeds mosquito larva.)

Treatment
· Quinine (a drug obtained from the bark of Cinchona tree) is used as an Antimalarial drug.
· Peludrine, Atabrin, Camoquinine, Chloroquinine are other drugs effective against malaria.
· Mefloquine (Larium) is used to treat multidrug resistance (MDR) for P. falciparum.
· 20th August is the Mosquito day whereas 25th April is the Malarial day.