This document discusses the life cycle and pathogenesis of Plasmodium vivax, the parasite that causes vivax malaria. P. vivax has a digenetic life cycle involving two hosts. In humans, it undergoes asexual reproduction in the liver and red blood cells. Mosquitoes ingest the parasite's gametocyte stages, where sexual reproduction occurs leading to sporozoite formation. Sporozoites are then transmitted to humans to continue the cycle, causing symptoms of malaria including fever and anemia. Diagnosis involves blood smear microscopy and treatment involves chloroquine and primaquine to prevent relapses.

2. Phylum
Sub phylum
Class
Sub class
Order
Genus

3.  Plasmodium is a genus of parasitic micro-organisms
known to cause malaria in humans.
 Parasites, like Plasmodium, are organisms that live in
or on other organisms (the hosts), to the detriment of
those organisms.
 Plasmodium can infect many different types of
animals, including reptiles, birds and mammals.
 These parasites are transmitted to vertebrate hosts
by insect (notably mosquito) vectors and cause
malaria in human.

4.  P. falciparum : Tropical and Subtropical areas of
Countries in S. America, Africa, and S.E. Asia.
 P. malariae : Tropical and subtropical areas of
Countries in S. America, Africa, and S.E. Asia
 P. ovale : Primarily in Sub-saharan Africa.
 P. vivax : Countries in S. America, India and S.E.
Asia.

7. Plasmodium vivax
 Plasmodium vivax lives as an intracellular parasite
in the red blood corpuscles (R.B.Cs) of man in the
form of its mature adult condition, called
trophozoite.

9. falciparum vivax ovale malariae
•numerous rings
•smaller rings
•No trophozoites
or schizonts
•cresent-shaped
gametocytes
•enlarged
erythrocyte
•Schüffner's
dots
•'ameboid'
trophozoite
•similar to P.
vivax
•compact
trophozoite
•fewer
merozoites in
schizont
•elongated
erythrocyte
•compact
parasite
•merozoites in
rosette

10.  Life cycle of Plasmodium vivax is digenetic i.e. they
complete their life cycle in two hosts:
1. Primary host or definitive host: Female
Anopheles mosquito is the primary host. The
organism which contains sexual phase of the
parasite and is regarded as definitive host.
2. Secondary host or intermediate host: human is
the secondary host. Human contains asexual phase
of the parasite and develops symptoms of disease
due to the presence of parasite and is termed as
secondary host.

11. Life cycle of Plasmodium vivax is divided into:
1. Asexual life cycle or schizogony in man
2. Sexual life cycle or sporogony in female
Anopheles mosquito

12.  Schizogony is the process of asexual reproduction by
which Plasmodium undergoes asexual multiplication
in liver cell and RBCs of man. It occus in human liver
cell (liver schizogony) and in RBC (erythrocytic
schizogony).
 When an infected female Anopheles mosquito bites a
healthy person, it injects thousands of sporozoites
along with saliva into the bloodstream. Inside liver
and RBC different form of sporozoite cause
infection.
Asexual cycle or Schizogony in man

13. Asexual cycle or schizogony in human is completed
in following phases:
1. Pre-erythrocytic schizogony
2. Exo-erythrocytic cycle
3. Erythrocytic cycle
4. Post-erythrocytic cycle
5. Formation of gametocytes

14.  When the sporozoites enters the blood it remains active
for about half an hour and disappears from the blood
circulation.
Then it enters into parenchymatous cell of liver (to
escape the phagocytic action of leucocytes) through
blood circulation by secreting lytic enzymes from the
apical cap.
 Sporozoites in liver cell grow in size and become
spherical in shape called schizonts. The nucleus of
schizont multiply asexually (multiple fission) and forms
thousands of merozoites. These gives pressure to the wall
of liver cell and liberated out in the form of cryptozoites
or cryptomerozoites through ruptured liver cell.

15.  It is completed in 8-10 days.
 The process of formation of many cryptozoites from
single sporozoites in liver cell is called pre-
erythrocytic schizogony.

16.  The cryptozoites are ready to infect the fresh liver cell
where they grow and become schizont. The same process
is repeated several times. The liberated merozoites in this
phase is called metacryptozoites.
 The process of formation of many metacryptozoites from
the cryptozoites in liver cell is called exo-erythrocytic
schizogony.
 Some metacryptozoites are smaller in size called micro
metacryptozoites and some are larger in size called
macro metacryptozoites.
 The micro metacryptozoites enter the red blood cells to
start the erythrocytic phase while the macro
metacryptozoites infects the fresh liver cells to continue
exo-erythrocytic phase.

17.  This cycle starts when the micro metacryptozoites enter
into erythrocytes. Single metacryptozoite enters into
single RBC and passes through trophozoite stage, signet
ring stage, amoeboid stage and schizont stage.
 When metacryptozoites invade the RBC it becomes
rounded with large nucleus and grows in size by
ingesting hemoglobin of corpusles. This stage of parasite
is called trophozoite stage.
 Inside the trophozoite, a large non-contractile vacuole
appears which pushes the nucleus towards periphery
and forms a ring like structure known as signet ring
stage.

18.  Trophozoites enlarges and vacuole starts disappearing
and develops pseudopodial processes in the cytoplasm
and changed into amoeboid stage. This stage is called
amoeboid stage.
 The amoeboid feeds completely the component of
corpuscles in the form of hemoglobin.
 The amoeboid trophozoites after feeding, becomes
rounded, grows in size and becomes erythrocytic
schizont. Asexual multiplication takes place in schizont
and forms merozoites which give pressure to the wall of
weak RBC and liberated out in the form of erythrocytic
merozoites.
 The merozoites are arranged towards the periphery due
to the presence of hemozoin at the center. The
arrangement is just like the arrangement of petals in rose
flowers. So this stage is called rosette stage.

19.  Numerous yellowish eosinophilic granules appear in
the cytoplasm of the host corpuscles which are called
schuffner’s granules. These dot are believed to be the
antigen excreted by the parasites.
 The process of formation of merozoites in the RBCs
from the metacryptozoites is called erythrocytic
schizogony.
 It completes about 48 hours.
 Many merozoites enter the fresh RBC and repeat the
erythrocytic cycle.

21.  Sometimes, some merozoites produced after
erythrocytic cycle invade the liver cell and undergo
another schizogonic development in the liver cell.
This is called post-erythrocytic cycle.

22.  After some generation of erythrocytic cycle, some of the
merozoites invade the new RBC. They grow in size but do not
develop into schizonts instead they develop into gametocytes.
 The gametocytes are of two types:
i. Macrogametocytes or female gametocytes: These are large
(10-12µ) and numerous in number. They have small compact
peripheral nucleus. They have reserved food materials and the
cytoplasm is dark in color.
ii. Microgametocytes or male gametocytes: These are smaller
(9-10 µ) motile and few in number. They have large centrally
placed nuclei. They lack reserved food and stains faintly hence
the cytoplasm is light in color and clear.

23.  Further development of gametocyte stop in man and
only possible in mosquito due to its low
temperature.
Inoculation
When an infected female Anopheles mosquito bites a
healthy person it suck his/her blood for meal, she
injects saliva containing sporozoites into the wound
through its needle like mouth parts. This is called
inoculation.

24. Pre patent period
The interval between inoculation and initiation of
erythrocytic cycle is called pre-patent period.
Incubation period
The period between the entry of parasite and
appearance of first symptoms is called incubation
period. It is about 14 days in P. vivax and P. ovale, 12
days in P. falciparum and 28 days in P. malariae.

25.  When female Anopheles mosquito bites an infected
persons, they suck the gametocytes and other stages
of erythrocytic cycle (e.g. erythrocytic merozoite)
along with blood. They reach the stomach where all
the stages along with RBCs are digested except
gametocytes.
 Now, the life cycle is continued towards the
completion by following processes:

27.  Process of formation of gametes from the gametocytes
is called gametogenesis.
 Formation of microgametes
Microgametocytes undergo ex-flagellation process in
the mid-gut of mosquito. The nucleus of
microgametocytes divides to form 6-8 daughter nuclei,
first division is meiotic. These nuclei move to periphery
along with cytoplasm, forming flagella like structure.
Thus 6-8 flagella like male gametes are formed from
each microgametocytes. The elongated structure are
called microgametes or sperms. The movement of
flagella causes the gametes to separate and move
actively in the stomach of mosquito in search of female
gametes.

28.  Formation of macrogametes
Macrogametocyte undergo some reorganization and
become female gametes or macrogametes or
megagametes.
The female gamete is non-motile and develops a
cytoplasmic projections called cone of reception or
fertilization cone on one side.

29.  One microgamete penetrates into macrogamete
through the cone of reception and fertilization takes
place known as syngamy.
A complete fusion of nuclei and cytoplasm of the
two gametes occurs, resulting in the formation of
diploid zygote or synkaryon.
Zygote form in stomach of mosquito about 9 to 10
days after the blood meal.
 NOTE: The process of fusion of male and female gametes
is called syngamy. Syngamy is anisogamous due to the
dissimilar structure of gametes. Hence, their fusion is
called anisogamy.

30. 3. Formation of ookinete
 After fertilization, the zygote remains rounded and non-
motile for some time. Then it becomes elongated and
vermiform known as ookinete.
Ookinete is motile and has pointed ends. It penetrates the
wall of stomach with the help of lytic secretion. It settles
into the inner portion of stomach wall.
4. Formation of Oocysts
 The ookinete changes into spherical shape, take nutrition
from the wall of stomach and get enclosed in a thin,
elastic and permeable cyst wall, such stage is called
oocyst stage or sporont.
 The cyst wall is secreted partly by ookinete and partly derived
from the stomach tissue of mosquito. Many oocysts (<500) are
seen on the stomach wall of infected mosquito. The ookinetes
fail to penetrate the stomach wall pass out from mosquito’s
body with faecal matter.

31. 5. Sporogony
 It is a phase of asexual multiplication.
 It is the process of formation of sporozoites from the
zygote nucleus by asexual multiple fission.
Oocysts matures and develops. The nucleus of oocyst
divides first by meiosis and then by mitosis, forming
large number of haploid nuclei (2-3 days) and forms
sporozoites forming cell known as sporoblasts.
 The nuclei of sporoblast again multiply and cytoplasm
gets constricted around them.
Thus the resultant structures in the sporoblasts elongate
to form slender or sickle shaped sporozoites.
Therefore, each oocyst fills with numerous sporozoites.
Now, these give pressure to the oocyst and due to which
the oocyst burst or rupture and thousands of sporozoites
are released in the body cavity (hemocoel) of mosquito.

32.  The sporozoites are very active and motile, then they
reach to the salivary glands of the mosquito.
Then the sporozoites are ready to infect the healthy
person after each bite. So when the infected mosquito
bites a healthy man, thousands of sporozoites are injected
into his blood along with saliva.

36.  Cause benign tertian malaria, a moderately severe
disease with high parasitaemia as species
preferentially infect young erythrocytes.
 Symptoms appear 7-10 days after infection and are
vague for 3-4 days ,developing to steady or irregular
low-grade fever then paroxysms with a regular 48
hour cycle.
 Splenomegaly is evident during the first few weeks
of infection and leukopenia is usually present.

37.  Severe complications are rare but P. vivax infections can
sometimes include cerebral malaria with neurological
signs, haemolytic anaemia, renal failure and pulmonary
failure.

38.  shaking chills that can range from moderate to severe
 high fever
 profuse sweating
 headache
 nausea
 vomiting
 abdominal pain
 diarrhea
 anemia
 muscle pain
 Convulsions
 bloody stools

39. 1. Demonstration of parasites by microscopy
 Diagnosis of malaria can be made by demonstration of
malarial parasite in the blood.
 Two types of smears are prepared from the peripheral
blood. One is called thin smear and the other is called
thick smear.
a. Thin smears: They are prepared from capillary
blood of finger tip.
 A properly made thin film will consist of an
unbroken smear of a single layer of red cells.
 Thins smears are air dried rapidly, fixed in alcohol
and stained by one of the Romanowsky stains such
as Leishman, Giemsa, Field's, or JSB stain

40. b. Thick smears :
 In a thick film, usually three drops of blood are spread
over a small area (about 10 mm).
 The amount of blood in thin smear is about 1- 1.5 μL,
while in a thick smear it is 3-4 μL.
 The thick film is dried and kept in a Koplin jar for 5-10
minutes for dehemoglobinization.
2. Fluorescence microscopy:
Kawamoto technique:
 Fluorescent dyes like acridine orange or
benzothiocarboxy purine are used, which stain the
parasites entering the RBCs but not white blood cells
(WBCs).
 This is a method of differential staining.

41. Positive P. vivax, P. ovate and P malariae cases are
treated with chloroquine 25 mg/kg divided over 3
days.
Vivax malaria relapses due to the presence of
hypnozoites in the liver.
For prevention of relapse, primaquine is given in a
dose of 0.25 mg/ kg daily for 14 days under
supervision.
Note: In case of chloroquine resistance: Quinine is
given in a dose of 600 mg 8 hourly for 7 days along
with doxycycline 100 mg/ day.

42. Chemoprophylaxis
o It is recommended for travelers going to endemic
areas as short-term measure.
o Chloroquine (300 mg) or mefloquine (400 mg)
weekly should be given 1 week and 2 weeks before
travel to endemic area respectively.
o Alternatively doxycycline (100 mg) daily can be
given from day l before travel.

43. Personal protection measures against mosquito bites
 Because of the nocturnal feeding habits of most
of Anopheles mosquitoes, malaria transmission occurs
primarily at night.
 Protection against mosquito bites include the use of
mosquito bed nets, the wearing of clothes that cover most
of the body, and use of insect repellent on exposed skin.
 The destruction of larvae by environmental management
and the use of larvicides or mosquito larvae predators,
and destruction of adult mosquitoes by indoor residual
spraying and insecticide-treated bed nets.

44.  As referred to, the parasite, in its mature adult
condition, is called trophozoite. The trophozoite is
amoeboid, uninucleated having vacuolated and
granular cytoplasm
 The ultra structure of Plasmodium vivax has been
revealed by the electron microscope. According to
electron microscopic studies, the Plasmodium in a
red blood corpuscle possesses a double membrane,
the plasma lemma closely applied to the cytoplasm.
The cytoplasm of Plasmodium vivax contains small
dense particles probably containing
ribonucleoproteins.