Saturday, May 27, 2017

Plasmodium vivax: Life cycle

Plasmodium is an intracellular, endoparasite and pathogenic parasite. There are 92 known species of Plasmodium  out of which 4 are known to cause different types of malarial fever in man. The different 4 species of Plasmodium and malaria caused by them are as in the table below:


Species of Plasmodium
Type of malaria( Disease)
P. vivax
Benign tertian malaria
P. ovale
Benign sub-tertian malaria
P. malariae
Benign quartan malaria
P. flaciparum
Malignant tertian malaria or cerebral malaria

Distribution: - Plasmodium is wide spread in tropical and temperate countries. The P. vivax is most widely distributed. It prevails mainly in temperate regions of the world. The P. flaciparum is confined to the warmer parts only. The P. malariae is like P. vivax in distribution while P. ovale , though is wide spread is the rarest of the four type.

In 1880, Charles Laveran discovered Plasmodium in human RBC. In 1897, Ronald Ross identified the oocyst of plasmodium in the gut wall of mosquito and shown the relationship of malaria with mosquito.In 1898, Amigo Bignami and Giovanni Grassi described the digenetic life cycle of Plasmodium.

Systematic position
Phylum:                    Protozoa
Subphylum:              Sporozoa
Class:                       Telosporea
Genus:                      Plasmodium
Species:                    vivax
Life cycle of Plasmodium vivax
P. vivax is most common human infecting malaria fever parasite. It causes benign tertian or vivax malaria. This malaria is characterized by a 48 hour cycle between the first fever and subsequent recurrence of fever. It is digenetic parasite with man being intermediate host and female Anopheles mosquito is primary host. It is intracellular parasite in man and lives in RBCs and liver cells while it is extracellular in mosquito and lives in alimentary canal and salivary glands.
Life cycle of plasmodium is complicated with asexual cycle called as schizogony  in man and sexual cycle called as gametogony and sporogony in mosquito. As sexual cycle takes place in mosquito, it is called as primary host. However, in medical science man is regarded as primary host.

Asexual cycle in man: A healthy man gets infected when an infected female Anopheles mosquito with sporozoites in its salivary glands, bites him/er for sucking blood. The mosquito punctures the skin by proboscis and first introduces some amount of saliva into blood stream and along with saliva thousands of sporozoites are inoculated in blood. The saliva is poured to prevent clotting of blood as it contains anticoagulant (anophiline).



Asexual cycle in man consists of pre-erythrocytic cycle, exo-erythrocytic cycle and erytrocytic cycle. The pre-erythrocytic cycle and exo-erythrocytic cycle are called as liver schizogony.
pre-erythrocytic cycle:- The sporozoites in human blood circulates for half an hour and then they enter inside liver cells from blood capillaries. After entering inside liver cells the sporozoites are now called as cryptozoites.They feeds up on cytoplasm and after few days they become spherical and non-pigmented shizont. The schizont divides by multiple fission called as schizogony to form large number of uninucleated cells called as crypomerozoites. They are liberatd when liver cells brust. This is the end of pre-eryhrocytic phase.



Exo-erythrocyic cycle: -   The cryptomerozoites enter inside fresh liver cells and becomes metacryptomerozoites. They undergo schizogony as in previous cycle to form thousands of metacryptomerozoites. This may be repeated several times and each time infecting new liver cells. All these are called as exo-erythrocytic cycles.
It is found that the metacryptomerozoites are of two types; smaller and more numerous are micro-metacryptozoites and they enter inside RBC to start erythrocytic cycle. The other types are larger and less in number are called as macro- metacryptozoites and they enter inside fresh liver cells to continue exoerythrocytic schizogony.
Pre-patent and incubation period:- The time period from infection up to first appearance of parasite in blood is termed as pre-patent period  and it varies from species to species. In P. vivax it is about 8 days.
The time period from infection up to first appearance of symptoms of malaria is called as incubation period. It is 10-17 days (average 14 days) in P. vivax.
Erythrocytic cycle:-  The micrometacryptozoits after coming in blood stream enter inside RBC and the erythrocytic cycle begins. It consists of following stages;
Trophozoit stage: Inside RBC the micro-metacryptozoites becomes rounded and are called as trophozoite.



Signet ring stage: The trphozoite  grows in size and a central vacuole appears in it and the nucleus is pushed into one side in peripheral region. This stage is called as signet ring stage as it looks like signet ring. It feeds upon cytoplasm of RBC and a food vacuole is formed in which digestive enzymes are formed. These enzymes begin proteolysis of haemoglobin which breaks down into protein (globin) and hematin. The protein is used as food by the parasite while hematin forms toxic malarial pigment haemozoin.
Amoeboid stage: A number of pseudopodial processes develop in the signet ring stage trophozoite and extends in cytoplasm of blood corpuscles. Now the trophozoite is called as amoeboid trophozoite.At this time a number of small red eosinophilic granules appear in the cytoplasm of RBC which are known as schuffner's granules or dots.
Schizont: The amoeboid trophozoit feeds actively for sometime and after that gets changed into rounded schizont and its size also increases. It now undergoes schizogony. Its nucleus divides into 12-24 nuclei and they get arranged at the periphery and cytoplasm surrounds them. Each nucleus with cytoplasm surrounding it forms an oval merozoite. The haemozoin gets accumulated at centre.  At this time the small merozoites remain arranged like the petals of rose flower so it is also called as rosette stage. The RBC ruptures and merozoites are released in plasma. The haemozoin is also released in plasma which causes the attack of malarial fever. These merozoites enter inside fresh RBC to repeat the erythrocytic cycle. The ruptured RBC and schizont(ghost) left behind are destroyed in spleen. The spleen is storehouse of malarial parasite in human body. One complete erythrocytic cycle takes 48 hours in P. vivax.
* Post –erythrocytic schizogony:- Sometimes some merozoites produced in erythrocytic schizogony enter inside liver cells and repeat schizogonic cycle in liver called as post-erythrocyic  schizogony.
*Formation of gametocytes:-  After repeated erythrocytic schizogony the merozoites loss the power of schizogony and after entering inside RBCs grow into rounded gametocytes. The gametocytes show sexual diamorphism and are of two types; smaller male or microgametocytes with large nucleus and larger female or megagametocytes with small peripheral nucleus. These gametocytes donot divide and remain as intracellular parasite within host's RBC until they die or are ingested by vector in which they continue their growth. For the growth of gametocytes low temperature is required.

Sexual cycle in mosquito:- When a female Anopheles mosquito sucks blood of the infected person containing  gametocytes in RBC. Any other stages of parasites and RBCs are digested but the gametocytes survive and they remain in stomach of mosquito. In mosquito sexual cycle is followed by asexual sporogony. The gametogony , fertilization and sporogony takes place in mosquito.
Gametogony:- The process of formation of gametes from gametocytes is called as gametogony or gametogenesis. The gametes are of two types; micro-gametes and mega-gametes.
According to Bano-1959, in Plasmodium reduction division takes place in the first division of zygote. Thus, only zygote is diploid while gametes and all other stages of life cycle are haploid as in higher plants. However, in other animals and most protozoan's, reduction division occurs during formation of gametes. Thus, only gametes are haploid while zygote and other stages are diploid.
Micro-gametes:-The male or micro-gametocytes undergo a process called as exflagellation in the midgut of mosquito. The nucleus of micro-gametocytes divides by mitosis to form about 6-8 haploid nuclei and they get arranged at periphery. The cytoplasm outgrows into long thin and flagella like projections and a daughter nucleus enters in each one of them. These projections break away as mature male or micro-gametes.
Mega-gametes: - The female or mega-gametocyte undergoes some reorganization and becomes a female or mega-gamete.
Fertilization:- A small cytoplasmic projection , called as cone of reception or cone of fertilization is formed in the posterior part of mega-gamete. The micro-gamete comes and enters inside mega-gamete through cone of reception and fertilization takes place. A complete fusion of nuclei and cytoplasm of two gametes occurs to form zygote with dipoloid nucleus or synkaryon.
Ookinete:- the zygote remain rounded and motionless for some time but soon it becomes elongated, motile and vermiform. It shows gliding movement and is known as vermicule or ookinete.
Under high power of magnification, a central irregular nucleus, dense cytoplasm, brown pigments, many mitochondria and ribosomes are present in ookinete. The motile nature of okinete is due to the presence of microtubules.
Encystment:- The ookinete penetrate the wall of stomach and remain just under the thin membrane which separates stomach from haemocoel. The ookinete becomes spherical and begins to encyst. The cyst wall is thin, membranous and elastic. It is partly secreted by ookinete and partly by wall of stomach of mosquito. The encysted zygote is called as oocyst or sporont. These oocysts grow in size and are seen outside of stomach as transparent rounded structures.
Sporogony:- The nucleus of oocyst  divides first by meiosis and subsequently by mitosis forming an enormous number of small haploid nuclei. At this time, the cytoplasm develops large vacuoles and numerous cytoplasmic masses are formed. Each daughter nucleus get arranged in the margin of cytoplasmic mass and later, slender and finger like projections are given out from these cytoplasmic masses and a daughter  nucleus move in to each of them. By this way about 10000 minute sickle shaped and slender sporozoites are formed. These sporozoites are released in the haemocoel of mosquito when mature oocyst ruptures. The sporozoites are motile and move to different organs and finally they penetrate salivary glands and remain there. It takes about 10-20 days for completion of sexual cycle. However, it depends up on temperature. About 200,000 sporozoites are present in the salivary glands of infected mosquito.



Types of malaria
There are 4 different types of malaria recognized on the basis of period of recurrence of fever.
* Tertian, benign or vivax malaria:- The causative agent is P. vivax. It remains characterized by the recurrence of fever in every 48 hrs or 3rd days. It is found worldwide, mainly in temperate areas. It does not result in the death of patient.
* Ovale or mild tertian malaria:- The causative agent is P. ovale. The fever recurs in every third day or 48 hrs. It is mainly found in tropical Africa. It is not so harmful.
* Quartan mlaria:- The causative agent is P. malariae. The fever recurs in every 4th day or 72hrs.Though it ordinarily does not prove fatal, chronic infections may give lethal kidney conditions. It is worldwide in occurrence. However, is confined to tropical and sub-tropical regions.
*Aestivo-autumnal, malignant tertian, cerebral malaria or pernicious malaria:- The causative agent is P. falciparum. The fever recurs in every 48 hrs. The fever is often fatal to the patient as it affects brain of patient. It is worldwide in occurrence mainly in temperate areas.
Quotidian malaria: - when mere than one species of Plasmodium infect patient the fever is repeated daily with an interval of 24 hrs.

Symptoms
The malaria is a dramatic disease with fever showing three successive stages;
Cold stage:-  At the onset of malaria fever the patient suffers from a sever shaking chill and feels very cold. This lasts for about 20 minutes to one hour.
Hot sage:-  As the chill subsides, body temperature increases to about 410C. The patient feels very hot with terrible headache. It lasts for one to four hours.
Sweating stage:- As the temperature lowers down, the patient sweats profusely. The fever comes down and the patient feels normal until next attack which takes at regular interval of 48 hrs in vivax malaria. The total duration of paroxysm is about 6-10 hours.
 The malarial fever occur when the schizonts in RBCs burst and the merozoites and haemozoin are released in blood plasma. The haemozoin is toxic and causes high fever and shivering.
Control of malaria
* Destruction of Anopheles mosquitoes:- Following methods can be used to kill them;
Killing by hands:- Mosquitoes which bite may be killed by hands.
Traps: - small boxes of wire gauze are used as trapper. Mosquitoes which enter inside the trapper are killed by closing them.
Fumigation:- Mosquitoes are killed and driven out by burning sulphur, tarcamphor, derivatives of naphtha, cresol etc. for fumigation.
Spraying:- Mosquitoes can de killed by spraying insecticides.
* Elimination of breeding places:-Water is drained off from areas with stagnant water like pools ponds, ditches, pits etc as they are breeding places of mosquito. If possible these breeding grounds may be filled with soil.
*Destruction of larvae and pupa of mosquitoes:- The aquatic larvae and pupa are killed by
Oil screens:- Water surface is covered by spraying petroleum, paraffin oil, or  kerosene oil. The thin surface of oil film prevents the larvae and pupa from normal respiration and they die.
Chemical larvicides:- The dusts containing Paris green, DDT or BHC are effective to kill larvae of mosquitoes.
Biological methods:- The larvicidal fishes like stickle-backs, minnows( Gambusia) and trouts feed upon larva of mosquitoes. The ducks, tadpole larva, insects like adult dragonfly etc fed upon larva and pupa of mosquitoes.
Prevention of infection
  The mosquitoes bite can be prevented by screening windows, doors and ventilations, using mosquitoes net, using anti-mosquito creams on exposed parts of body or by fumigation etc.
Treatment

  The medicines used for treatment of malaria are Quinine, Camoquin, chloroquinine, Daraprim, Paludrine, pentaquine etc. The Quinine is extracted from the bark of Cinchona tree. The Daraprim  (generic name Pyrimidine) is the most potent and effective.