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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Discipline Courses-I
Paper: Divesity and Evolution of Choradata-I
Lesson: Life Cycle, Pathogenicity and Prophylaxis of Plasmodium
Lesson Developer: Anubha Das
College/Department: Zakir Husain College, University of Delhi

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Table of Contents

Taxonomic position
Geographical distribution
Habit and habitat
Life cycle of P. vivax
The Human phase
Exoerthrocytic stage
Erythrocytic stage
The mosquito phase: Sporogony
Incubation period
Initial symptoms
Malarial paroxysm
Mode of infection
Infective stage
Source of infection
Transmission ways
Factors affecting transmission
Susceptible population

Institute of Life Long Learning, University of Delhi

Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Malaria parasites belongs to genus Plasmodium, are classified in the domain Eukarya, kingdom
Protista, Phylum Apicomplexa. All members of the phylum Apicomplexa are obligate
intracellular parasites of vertebrates (humans, birds, lizards, rodents, and primates) causing
considerable damage and even leading to death of the host.

Fig. 1. Cycle of Malaria

Source: ILLL in house
Life cycle of a typical sporozoan (class Sporozoea) includes 3 distinct stages: sporogony,
schizogony (or merogony) and gamogony (or gametogony) and there is alternation between
an invertebrate (mosquito) and a vertebrate (lizard, bird, mammal) host.
The disease is widespread in tropical and subtropical regions in a broad band around the
equator, including much of Sub-Saharan Africa, Asia, and the Americas. Plasmodium is an
ancient organism and it is been with us since long.

Value addition: Ronald Rosss poem!

Heading text: The heart of poet and brain of a scientist!
Body text: Ronald Ross penned an optimistic poem on August 21, 1897, shortly after
discovering malaria parasites in mosquitoes: The poem unfortunately overstated the prospects
for a victory over malaria as, we after 113 years, are still fighting to control the deadliest
This day relenting God

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Hath placed within my hand

A wondrous thing; and God
Be praised. At His command,
Seeking His secret deeds
With tears and toiling breath,
I find thy cunning seeds,
O million-murdering Death.
I know this little thing
A myriad man will save.
O Death, where is thy sting?
Thy victory, O Grave!

Source: http://www.pnas.org/content/104/29/11865.full.pdf
Value addition: Video
Heading text: No ordinary mosquito bite!
Body text: No ordinary mosquito bite!
Source: http://www.youtube.com/watch?v=IVbq2yQH52g
The genus Plasmodium was described in 1885 by Ettore Marchiafava and Angelo Celli. At
present, more than 200 species of this genus are identified. It is also known as the malarial
Out of the over 200 known species of Plasmodium, at least 11 species infect humans. Other
species infect other animals, including monkeys, rodents, birds, and reptiles. The parasite
always has two hosts in its life cycle: a vectorusually a mosquitoand a vertebrate host.
Plasmodium falciparum (Welch, 1897), Plasmodium vivax (Grassi e Feletti, 1890), Plasmodium
malariae (Laveran, 1881) and Plasmodium ovale (Stephens, 1922) are the four species of
Plasmodium known to cause malaria in human. The deadliest of the four species of the
parasite is Plasmodium falciparum.

Value addition: Did you know?

Heading text: A fifth species of Plasmodium hosted by man!
Body text: A new species of Plasmodium has been discovered in Malaysian Borneo
Plasmodium knowlesi, which jumps the species barrier, spreading from monkeys to humans.
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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

So there are now five species of malaria parasites that can be hosted by humans.
Source: http://www.parasitesandvectors.com/content/pdf/1756-3305-1-26.pdf

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Value addition: (Biographic sketch) An inspiring story.hard work

and consistent approach really pays off!
Heading text: Sir Ronald Ross and the Discovery that Mosquitoes Transmit
Malarial parasite.

Body text: Sir Ronald Ross was born to Sir C.C.G. Ross,
a General in the Indian Army and his wife Matilda in 1857
in Almora, India. He was sent to England for education at
the age of eight where he spent much of his childhood with
an aunt and uncle. During his early years he developed
interests in poetry, literature, music, and mathematics, all
of which he continued to engage in for the rest of his life.
In 1881, he returned to India, as medically qualified
(MRCS and LSA) and joined the Madras branch of the
Indian Medical Service.
In 1892, Ross became interested in malaria even though
originally he doubted the parasites existence. In 1894,
Patrick Manson, considered by many to be the father of
tropical medicine, showed him 'Laveran's bodies' (malaria parasites), and convinced him of
the possibility that mosquitoes carried malaria. Eventually he became an enthusiastic
convert to the belief that malaria parasites were in the blood stream. On returning to India,
Ross rejoined his regiments at Secunderabad, where he started breeding mosquitoes and
fed them on malaria patients in order to experimentally prove his theory.
At the end of May 1896, on the basis of his observation he wrote to Manson: "The belief is
growing on me that the disease is communicated by the bite of the mosquito... She always
injects a small quantity of fluid with her bite - what if the parasites get into the system in
this manner." Unfortunately, he could not prove his theory as he was using Culex
mosquitoes, which do not transmit malaria.
After his return to Secunderabad, Ross decided to continue his investigations with mosquito
species from a highly malarious area. He went to the notoriously malarious valley of Sigur
Ghat and three days later he contracted the disease, despite having slept under a mosquito
net and behind closed windows. After returning to the Ghat, he got interested in mosquito
species he had not seen before.
In mid-August 1897, unfamiliar larvae brought by his assistants hatched into similar
mosquitoes that Ross had found in Sigur Ghat. Ross could not find anything after dissecting
the mosquito. They were fed on a patient called Husein Khan but nothing was found when
they were dissected.
More mosquitoes hatched out and were fed, and by 20 August 1897 Ross was down to his
last two mosquitoes. He dissected one and found nothing - until he got to the stomach,
"when I saw a clear and almost perfectly circular outline before me of about 12 microns in
diameter. The outline was much too sharp, the cell too small to be an ordinary stomach-cell
of a mosquito. I looked a little further. Here was another, and another exactly similar cell."
The following day Ross killed his last mosquito and found similar but much larger cells. He
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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

wrote to Manson with his exciting news: "Now prick up your ears because the hunt is up
Ross got his work verified by a colleague, Surgeon-Major John Smyth and took ten days'
leave to write a paper, 'On some peculiar pigmented cells found in two mosquitoes fed on
malarial blood'. He sent this off immediately to the British Medical Journal, which took three
months to publish it.
By that time, Ross had been transferred to a small and isolated station called Kherwara in
Rajastan, which was conspicuously free of malaria. But he continued his research into
malaria in India, using birds as experimental model. By July 1898, he had demonstrated
that mosquitoes could serve as intermediate hosts for bird malaria. He found that the
malaria parasites in the mosquitoes migrate to the insects' salivary glands, which gets
transmitted to other birds by bite of infected mosquito.
He sent a copy of his report 'On the cultivation of Proteosoma labbe 1898' written for the
Director General of the Indian Medical Service to Patrick Manson. In the Annual Meeting of
the British Medical Association in Edinburgh, Manson presented report on Ross's work on
the oocysts in mosquitoes' stomach and also his telegraph, which stated that the parasite
was transferred through the vector's bite.
In 1902 he became the first Briton to win the Nobel Prize in Physiology and Medicine. He
died, after a long illness, at the Ross Institute on 16 September 1932.

Source: http://malaria.wellcome.ac.uk/doc_WTD023869.html and


Value addition: Interesting to know!

Heading text: An ordinary looking building with an extra-ordinary past!
Body text:

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Source: http://www.osmania.ac.in/srrip/photo%20gallary/RossAttributes.jpg and


Taxonomic position
Kingdom: Protista
Phylum: Apicomplexa
Class: Sporozoa
Genus: Plasmodium
NOTE: Vth ed. Barnes book has been consulted for classification

Geographical Distribution
Table 1. Geographical distribution of four species of Plasmodium
P. vivax

P. falciparum

Widespread in
tropical and
subtropical areas of
Central and South
America, India and
South East Asia.
Range extends into
temperate areas
Relatively uncommon
in Africa

Widespread in tropical
and subtropical areas of
Central and South
America, Africa and
South East Asia

P. malariae
Tropical and
subtropical areas of
Central and South
America, Africa and
South East Asia

P. ovale
tropical Africa,
especially Sub
Saharan Africa

Occurrence of malaria depends mainly on climatic factors such as temperature, humidity,

and rainfall. Malaria is more prevalent in tropical and subtropical areas, where

Anopheles mosquitoes get optimum condition for survival and propagation.

Malaria parasites can complete their growth cycle in the mosquitoes ("extrinsic
incubation period").

Temperature is particularly critical in case of malaria. In many malaria-endemic countries,

malaria transmission does not occur in all parts of the country and also may not occur
throughout the year. Transmission will not occur

At very high altitudes

During colder seasons in some areas
In deserts (excluding the oases)
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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

That is why in areas closer to the equator

Transmission is more intense
Malaria is transmitted year-round.
The highest transmission is found in Africa South of the Sahara and in parts of Oceania such
as Papua New Guinea.
In cooler regions, transmission will be less intense and more seasonal. There, P. vivax might
be more prevalent because it is more tolerant of lower ambient temperatures.
In many temperate areas, such as Western Europe and the United States, malaria has been
eradicated through economic development and public health measures. However, most of
these areas have Anopheles mosquitoes that can transmit malaria, and reintroduction of the
disease is a constant risk.

Fig.2. Malaria-endemic countries



The vertebrate host include human, monkeys, rodents, birds, and reptiles.

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

In the life cycle of Plasmodium, a female Anopheles mosquito (the definitive host) transmits a
motile infective form (called the sporozoite) to a vertebrate host such as a human (the
secondary host), thus acting as a transmission vector. All the Plasmodium species causing
malaria in humans are transmitted by mosquito species of the genus Anopheles. There are
seven species of Anopheles mosquito found to cause malaria in humans in India. These are:
A. culicifacies

A. stephensi

A. phillippinensis

A. sundaicus

A. fulviatilis

A. maculatus

A. minimus
Both sexes of mosquitoes live on nectar. Because nectar's protein content alone is
insufficient for oogenesis (egg production) one or more blood meals is needed by the female
so only female mosquitoes bites.

Value addition: Interesting fact

Heading text: Malarial vector
Body text: Species of the mosquito genera Aedes, Culex, Culiseta, Mansonia and
Theobaldia can also transmit malaria but not to humans. Bird malaria is commonly
carried by species belonging to the genus Culex. Ross who worked with species from
the genus Culex discovered the life cycle of Plasmodium.
Source: ILLL in house

Symptomatic as well as tolerant humans with high parasitemia count to infect mosquitoes. A
person with gametocytes in the circulation is a carrier or reservoir. Gametocytes do not
develop further or divide in the vertebrate host and unless taken up by the vector mosquito,
they die in a few days.

Life cycle and Morphology of Plasmodium vivax

Life cycle of Plasmodium is divided into two phases:

Asexual phase: occurs in humans (intermediate host of Plasmodium).

Sexual phase: occurs primarily in the female Anopheles mosquito (definitive host of

This alteration of generation i.e. alteration of asexual phase and sexual phase is in
complete synchronization with alteration of hosts. The asexual phase taking place in the
human is followed by the sexual phase in the mosquito. As the sexual phase is completed in
the mosquito, it is considered as the definitive host of Plasmodium parasite. Human
beings are the intermediate host as the asexual multiplication takes place here.

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Fig.3. Life cycle of Plasmodium

The malaria parasite life cycle involves two hosts: Anopheles mosquito and Human where the
parasite complete its sexual and asexual phase of lifecycle respectively. During a blood meal,
a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host
Sporozoites from the blood capillaries goes into hepatocytes

and mature into hepatic

schizonts through exoerythrocytic schizogony

, which rupture and release merozoites
. (In P. vivax and P. ovale a dormant stage [hypnozoites] can persist in the liver and
cause relapses by invading the bloodstream weeks, or even years later.) After this
initial replication in the liver (exo-erythrocytic schizogony

), the hepatic merozoites released

from liver cells invade RBC and undergo asexual multiplication (erythrocytic schizogony)
Merozoites infect red blood cells

. The ring stage trophozoites mature into erythrocytic

schizonts, which rupture releasing merozoites

. Some parasites differentiate into sexual

erythrocytic forms (gametocytes)

. Blood stage parasites are responsible for the clinical
manifestations of the disease. The gametocytes, male (microgametocytes) and female
(macrogametocytes), are ingested by an Anopheles mosquito during a blood meal
parasites multiplication in the mosquito is known as the sporogonic cycle

. The

. While in the

mosquito's stomach, the microgametes penetrate the macrogametes generating zygotes

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

The zygotes in turn become motile and elongated (ookinetes)

of the mosquito where they develop into oocysts

which invade the midgut wall

. The oocysts grow, rupture, and release

, which make their way to the mosquito's salivary glands. Inoculation of the

sporozoites into a new human host perpetuates the malaria life cycle

Table 2. Various morphological form of Plasmodium vivax













schizogony or





schizogony or

tic schizont
or meront






schizogony or





Relapse infections
of malaria

Signet ring




feeding stage







feeding stage




















Gut wall




Inoculated in
human during
blood meal from
where they
invade hepatocyte

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Source: ILLL in-house

The Human Phase

Blood meal acts as a protein source for egg production in female mosquitoes. In the female
mosquitoes, there is a continuous cycle of blood meal and oviposition. The female mosquito
repeatedly contacts the vertebrate host, ingests the malarial parasites, followed by the
multiplication and maturation of the parasites inside the mosquito, and their transmission to
other individual hosts during subsequent feedings.
Human infection comes through the bite of the infective female Anopheles mosquito. The
sporozoites, which are infective forms of the parasite, are present in the salivary glands of
the mosquito. They are injected into blood capillaries when the mosquito feeds on blood after
piercing the skin.

Value addition: Did you know?

Heading text: Plasmodium and Nobel prize!
Body text: Charles Alphonse Laveran, a French military doctor, won Nobel Prize in
1907 for the discovery of the malarial parasite, Plasmodium, in human blood samples
(1880). He donated the prize money to the Pasteur Institute for the creation of a
laboratory devoted to tropical diseases. He died in Paris on May 18, 1922.
Source: http://www.cdc.gov/malaria/history/laveran.htm

Fig.4. Anopheles stephensi mosquito is obtaining a blood meal from a

human host through its pointed proboscis. Note the droplet of blood being
expelled from the abdomen after having engorged itself on its hosts blood. This mosquito is a
known malarial vector with a distribution that ranges from Egypt all the way to China.
Source: http://en.wikipedia.org/wiki/File:Anopheles_stephensi.jpeg

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Fig.5. A female mosquito inoculating the human host with sporozoites

Around 10-15 sporozoites are injected at a time but even hundreds may be introduced in case
of heavy infections. The sporozoites pass into blood stream, where many are destroyed by the
phagocytes, but some reach the liver and enter the hepatocytes (liver cells).

Exo-erythrocytic (Tissue) Stage

Fig.6. Process of Exo-erythrocytic Schizogony.

Source: ILLL in house
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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Fig.7. Sporozoites making an entry and developing in a hepatocyte

Source: http://www.nature.com/nrd/journal/v8/n11/images/nrd2960-f1.jpg
Here, it undergoes a process of asexual replication to give rise to a schizont. During this preerythrocytic schizogony or merogony the sporozoites that are elongated spindle-shaped
bodies change the shape and tend to become somewhat rounded inside the liver cells. The
parasite invades and develops in a nucleated liver cells of host. The sporozoites grow in size
and undergo repeated nuclear division to form several daughter nuclei, each of which is
surrounded by cytoplasm. This stage of the parasite is called the pre-erythrocytic or
exoerythrocytic schizont or meront. The hepatocyte is distended by the enlarging schizont
and the liver cell nucleus is pushed to the periphery and there are no pigments in liver
schizonts, unlike erythrocytic schizogony.

Fig.8. A developing schizont in hepatic cell

At the end of the pre-erythrocytic stage of 6-16 days (depending on the Plasmodium sp., after
the time of infection), the cell containing the schizont ruptures releasing the merozoites into

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

the surrounding tissue and blood circulation. While some are phagocytized,most of them
invade the red blood cells present in the sinusoids of the liver.

Fig.9. The exit from liver cells

The pre-erythrocytic phase is asymptomatic phase. Neither any clinical symptoms
nor any pathological damage is produced by the parasite in this pre-erythrocytic
phase. Blood is sterile and the parasite is not susceptible to drugs in the tissue
The size of mature schizont and the number of merozoites produced also vary with the species
of parasite. The merozoites enter the blood stream and infect erythrocytes by a process of
invagination. The interval between the entry of the sporozoites into the body and the time
when malaria parasites first appears in the blood is called pre-patent period. It is
different from the incubation period, which is the first appearance of clinical symptoms after
In the human malarial species, it was originally thought that there are two successive preerythrocytic cycles, but it is now known that in two species of human malarial parasite i.e.,
Plasmodium vivax and P. ovale some sporozoites multiply inside hepatocytes promptly to form
schizonts i.e., some of the liver sporozoites immediately start the exo-erythrocytic schizogonic
cycle, while others remain in the liver as hypnozoites (Greek hypnos-sleep; zoon= animal).
Hypnozoites can remain dormant in the liver for months to years developing into infective form
leading to relapse infections. This is called secondary exo-erythrocytic cycle.The triggers
that activate the hypnozoites to become schizonts and release merozoites are unknown.

Erythrocytic Stage
It was believed earlier that the merozoites released from a schizont directly penetrate the
membrane of a red blood cell and then develop but now it has been established that the
merozoites enter erythrocytes by endocytosis. This key event in the malarial life cycle has
been extensively examined, as the inhibition of this process can be regarded as a crucial goal
in the development of a malarial vaccine.
The invasion of erythrocyte involves recognition and attachment of the merozoites to the
erythrocyte membrane. If, on initial contact with an erythrocyte, the apical complex end of the
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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

parasite is not directed towards the blood cell surface, a re-orientation takes place. After reorientation, some deformation of the erythrocyte membrane may occur and invagination and
endocytosis follows.
Once merozoites invade red blood cells, they feed on the haemoglobin and divide mitotically to
form an erythrocytic schizont. The merozoites are pear-shaped bodies and enter the RBCs by
endocytosis by creating a pit on RBCs membrane. The process of entry into the RBC takes
about 30 seconds.

Value addition: Interesting to know!

Heading text: What is so special about the proteins present on
Red Blood Cells?
Body text: The receptor for merozoites is glycophorin, a major glycoprotein on
the red cell. The differences in the glycophorins of red cells of different species may
account for the species specificity of malaria parasites.
Source: Textbook of Medical Parasitology, Paniker, C.K.J 6TH ed. 2007
After making its entry into RBC the merozoites rounds up and looses its internal organelles
(especially apical complex). The feeding stage of parasite is called trophozoite (trophosgrowth). The parasite, inside RBC has a central vacuole and cytoplasm is pushed on the
periphery with nucleus situated at one pole. When stained with Giemsa stain, the cytoplasm is
stained blue and nucleus red while the central vacuole remains unstained giving the parasite
an annular or signet ring appearance. These young parasites are therefore called the ring
forms or early trophozoites. It grows at the expense of the erythrocyte.
The parasite feeds on the haemoglobin of the erythrocyte but doesnt metabolise it completely
leaving behind a haematin-globin pigment as residue called as the malarial pigment
(earlier known as haemozoin pigment). These iron containing pigments keep on accumulating
in the body of parasite as dark granules and becoming more prominent with time as the
parasite grows.

Fig.10. Signet ring forms Plasmodium vivax trophozoites inside a red

blood cell
Source: http://eol.org/pages/2908737/details
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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Fig.11. Cycles of asexual parasite replication inside red blood cells.

throcyte within seconds (1), initiating a new erythrocytic cycle.
Source: ILLL in house

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Value addition: Interesting to know!

Heading text: The sickle cell trait provides advantage in malaria
endemic regions
Body text: In areas where malaria is endemic, sickle cell trait provides a survival
advantage over people with normal hemoglobin. People particularly children infected with P.
falciparum are more likely to survive the acute illness if they have a sickle cell trait. The
reason for resistance seems to be that as plasmodium parasites grow in the erythrocytes,
they lower the intracellular pH and generate hydrogen peroxide. The lower pH promotes
sickling of the erythrocytes and the hydrogen peroxide damages cell membranes, which
become more permeable to K+. the resulting intracellular decrease in K+ kills the parasite.
Source: Ahmed,N., Dawson, M., Smith, C and Wood, Ed ., Biology of Disease.

The malarial pigment is released when the parasitized cells rupture and is taken up by the
reticuloendothelial cells. The ring form becomes irregular in shape as it develops further and
enlarges in size. This is called the amoeboid form or late trophozoite. On the inner surface of
the erythrocyte the membrane of developing parasite starts accumulating and gives the
appearance of clefts on the erythrocyte surface.
After a period of growth, the trophozoite divides asexually by process of erythrocytic schizogony.
Division of nucleus 3-5 times produces a variable number of small nuclei. This stage of parasite is
called the schizont or meront (formerly known as segmenter or rosette forms). Initially, the
nucleus divides but the cytoplasm remains undivided, this stage is referred to as early schizont.
This is followed by the division of cytoplasm, surrounding each daughter nucleus and forming a
late schizont. The mature schizont is the fully-grown form, in which a number of small merozoites
are seen, each having a nucleus with surrounding cytoplasm. After the completion of schizogony,
the red cell bursts and the merozoites are released into the blood stream.

Value addition: Activity

Heading text: Identifying the various stages of malarial parasite.
Body text: In the laboratory, try to locate and identify the various stages of
malarial parasite present in a blood film from a person infected with Plasmodium sp.

Source: self created (author)

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Fig.12. Structure of a merozoite (showing various antigens)

Source: http://www.microbiologybytes.com/introduction/malaria/Malaria.gif
The merozoites then invade fresh red cells to produce another generation of parasites. This
repeated erythrocytic cycle of schizogony leads to a progressive increase of parasitaemia
until immune system of the host body slows down this process.

Value addition: Interesting facts

Heading text: Merozoites show a distinct preference for
erythrocytes of a certain age
Body text: In some species, merozoites show a distinct preference for erythrocytes of
a certain age. Many avian species attack almost exclusively the young erythrocytes. In
the human plasmodia, the merozoites of P. vivax attack young immature corpuscles
(reticulocytes) whereas those of P. malariae attack older ones, and those of P. falciparum
indiscriminately enter any available. This partly explains the virulence of P. falciparum
infections in which 10 percent or more of the erythrocytes may be attacked, whereas P.
vivax seldom occurs in even 1 percent of the corpuscles and P. malariae seldom in more
than 0.2 percent.

Source: Author

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

All schizonts release their merozoites within a period of several hours together with a pigment
and other waste products, and there is a sudden paroxysm of fever in the host, characterised
by a marked rise in temperature. This periodicity is one of the most remarkable features of
malarial organisms.The length of cycle is of 48 hours in P. vivax.
After a few cycles of erythrocytic schizogony, some merozoites that infect red blood cells do
not proceed to become schizonts, but instead develop into sexually differentiated forms, the
gametocytes. The precise mechanism for this differentiation remains unknown but it is
thought that the development of host antibodies may play a large part in the process, other
factors include stress due to rising parasitaemia, the effects of drug suppression, and nutrient
depletion. The gametocytes grow in size till they almost fill the red blood cell, but the nucleus
remains undivided. Development of gametocytes generally takes place within the internal
organs such as spleen and bone marrow, and only the mature forms appear in circulation. The
mature gametocytes are round in shape and female gametocyte is always larger
(macrogametocyte) than male gametocyte (microgametocyte). A person with gametocytes
in the circulation is a carrier or reservoir.
Gametocytes do not develop further or divide in the vertebrate host and unless taken up by
the vector mosquito, they die in a few days. The process of differentiation of gametocytes is
called gametocytogenesis.

Value addition: Video

Heading text: Plasmodium Life cycle in Human
Body text:
Life cycle of Plasmodium in Human host
Source: http://www.youtube.com/watch?v=1UTJ38D0ukw
The Mosquito Phase
During blood meals taken from persons infected with malarial parasites, the mosquitoes pick
up both the asexual and sexual forms of parasite. The asexual forms are digested, but the
gametocytes are set free in the stomach and undergo further development. The cells rapidly
undergo gamete production. This marks the beginning of gametogenesis and sexual cycle.
A reorganization in the macrogametocyte results in the formation of the female gamete. The
formation of male gametes is however an explosive phenomenon and the ultrastructural
changes are rapid and stunning. A complex cytoplasmic reorganization takes place, involving
rapid nuclear divisions, which result in the production of 8 motile haploid gametes each
provided with an actively motile, whip-like filament (flagella). These flagella, which are male
gametes (microgametes) lash about for sometime and then break free. This process of male
gamete formation from gametocyte is called exflagellation.

Value addition: common misconception

Heading text: There is a difference between Gametocytogenesis
and Gametogenesis
Body text: It is not unusual to get confused between the two terms though there
exists a huge difference between the two. The
formation of gametocytes or cells
which give rise to gametes is known as gametocytogenesis and in case of the
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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

malarial parasite the process takes place inside the human body while the formation
of gametes from gamete producing cells is known as gametogenesis and in case of
malarial parasite this happens inside the body of mosquito host.
Source: http://encyclopedia.thefreedictionary.com

Fig.13. Ultrastructure of exflagellated Plasmodium

Source: http://www.impactmalaria.com/web/malaria_training/sexual_stages/gametogenesis
A change from a warm blooded animal to a cold blooded animal, pH and redox potential are
the factors which are responsible for the gametogenesis to take place.
Once a microgamete fertilises a macrogamete (which happens in half to two hours after the
blood meal), the resulting zygote develops into a motile elongated ookinete and develops
an apical complex, anteriorly.
The ookinete penetrates the gut wall of the mosquito and develops as an oocyst between
the epithelium and the basement membrane. It changes the shape and becomes round
with an elastic membrane. This stage is called oocyst. Ronald Ross discovered these
pigmented oocysts in the stomach of mosquito for the first time, a discovery that
established the mosquito transmission of malaria.

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Fig.14. Oocysts on the stomach wall of a mosquito

Source: http://ipmworld.umn.edu/chapters/curtiscf.htm
The oocyst matures in 10- 20 days depending upon temperature and species. The chromatin
divides repeatedly. This sporogony leads to the development within the oocyst of about a
thousand sporozoites, each with a central nucleus and an anterior apical complex.

Fig.15. Sporozoites after dissection of an infected mosquito

Source: http://www.impact-malaria.com/web/malaria_training/sexual_stages/sporogony_
The mature oocyst bulges into the body cavity of the mosquito, and when it ruptures the
sporozoites enter the haemocoel. The sporozoites reach the salivary glands of the mosquito
and enter the salivary duct. The time taken to complete sporogony in mosquito is about 1-4
weeks; depending on the temperature and the species. The mosquito is now infective and
when it feeds on humans, the sporozoites are injected into the skin to initiate human infection
and a new cycle begins.
Period of time required for the development of the parasite from the gametocyte to sporozoite
stage in the body of the mosquito is called extrinsic incubation period. The morphological
cycle of maturation of gametocytes somewhat corresponds to the period of infectivity to
mosquitoes. A single mosquito may remain infective throughout its life.
Such a
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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

synchronization of gametocyte and mosquito cycles have a marked selective advantage
making sure that the parasite is transferred to the vertebrate host and the life cycle continues.

Value addition: Video

Heading text: Plasmodium Life cycle
Body text:
Life cycle of Plasmodium

Source: http://www.youtube.com/watch?v=I_qSrFPjtQw
Value addition: Activity (choose the correct option)
Heading text: Lets check our understanding about the life cycle
of malarial parasite.
Body text:

Source: self created (author)

All of the pathology of malaria is due to erythrocyte destruction by multiplying parasites.
The disease process in malaria occurs due to:

Local and systemic response of the host to parasitic antigens.

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Tissue hypoxia caused by reduced oxygen delivery because of obstruction of blood

flow by the parasitized erythrocytes.
Anemia caused by destruction of large number of red cells.

Incubation period: The symptoms do not appear immediately after humans get
infected with Plasmodium sporozoites. The time interval between the infective bite of
mosquito and onset of clinical symptoms is called the incubation period.
During this period, sporozoites reach liver for exoerothrocytic schizogony followed by
erythrocytic schizogony in RBC to produce sufficient erythrocytic merozoites to cause clinical
symptoms. The incubation period in P.vivax varies from 8-31 days.

Initial clinical symptoms: The initial signs and symptoms of include: headache,
fever, shivering, joint pain, vomiting, hemolytic anemia, low blood pressure, jaundice,
anorexia, hemoglobin in the urine, retinal damage and convulsions. The initial symptoms of
malaria are flu-like and can resemble other conditions such as septicemia, gastroenteritis,
and viral diseases and it is for this reason that malaria is frequently called The Great

Fig.16. Symptoms of Malaria

Source: http://en.wikipedia.org/wiki/File:Symptoms_of_Malaria.png

Main clinical manifestations:


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Malarial paroxysm: It is the classical manifestation of acute malaria characterized by

fever, chill, and rigor. Fever is the key clinical manifestation caused by the release of
merozoites (asexual schizogonic developmental cycle) by rupture of schizont-infected red
blood cell. Fever is irregular and does not show any distinct periodicity pattern. It lasts for 2
hrs to 6 hrs. High fever reaching 40.6 degree C (105 0 F), dry skin and often headache,
nausea and vomiting are present in this stage.
High Fever (HYPERPYREXIA) may also be characterized by incontinence of urine and feces
mental disorientation, delirium and coma.The timing of fever cycle is 48 hours (tertian
fever) in P. vivax and P. ovale infections.
Each paroxysm shows a succession of three stages:
1.COLD STAGE: This is characterized by sudden onset of fever with rigor and sensation of
extreme cold. Patient desires to be covered with blankets. This stage lasts for 15 minute
and one hour.
2.HOT STAGE: Temperature may rise to 41 degree C (106 degree F). Patient feels burning
hot and casts off his clothes. There is intense headache. This stage lasts from 2 to 6 hours.
Chill subsides.
3.SWEATING STAGE: Fever comes down with profuse sweating. This stage lasts from 2 to
4 hours. Temperature drops rapidly to normal and skin is cool and moist. The classical 3
stages (cold, hot and sweating) may not always be observed due to maturation of
generations of the parasite at different times.

Value addition: Did you know?

Heading text: Types of Malaria
Body text:
1.TERTIAN, BENIGN TERTIAN OR VIVAX MALARIA: The causative agent of this
type of Malaria is P. vivax. It is characterized by the recurrence of fever every third
day, i.e., after 48 hours. This type of malaria does not result in death of the patient.
The incidence of the disease is worldwide, mainly in temperate regions.
2.QUARTAN MALARIA: P. malariae is the causative organism of quartan malaria,
which is characterized by the recurrence of fever every fourth day, i.e., at intervals
of 72 hours. It is well known for its longevity, 40 years or more in untreated persons.
Though it ordinarily does not prove fatal to the patient, the chronic infections
sometimes give rise to lethal kidney conditions. The disease is of worldwide
occurrence, but it is mainly confined to tropical and subtropical regions.
3.OVALE OR MILD TERTIAN MALARIA: This type of malaria resembles very much
to the tertian malaria and is caused by P. ovale. The fever recurs every third day or
at a intervals of 48 hours. Ovale malaria is not greatly harmful and is mainly
confined to tropical Africa.
P. falciparum. In this also the fever cycle is of 48 hours. The fever is often fatal to
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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

the patient as it affects the brain. Its incidence follows that of P. vivax.
5.QUOTIDIAN MALARIA: When more than one species of plasmodium infect the
patient, or when 2 or 3 generations of parasites mature on successive days, the
fever is repeated daily with an interval of 24 hours.

Fig.Tertian and Quatran fever patterns in Malaria


Source: http://en.wikipedia.org/wiki/File:Malaria_fever.svg
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Anemia: It is the most immediate pathologic consequence of malaria.Reasons for origin of

anemia are:
Destruction of erythrocytes on liberation of merozoites.
Suppression of red cell production in the bone marrow.
Infected erythrocytes become more fragile, rupture easily and are destroyed.
The enlarged spleen due to malarial infection releases a lytic substance, lysolecithin,
which destroys erythrocytes.
Malarial parasites produce haemolysin (an antibody), which brings about haemolysis
of some normal erythrocytes.
Hepatosplenomegaly: Liver becomes enlarged as kupffer cells increases in number and
their cytoplasm is filled with parasites, malarial pigment and cellular debris.
Spleen is markedly enlarged (SPLENOMEGALY). In acute infection, spleen is soft with a thin
capsule moderately enlarged and the splenic substance is congested. But in chronic disease,
spleen is enlarged, hard with thick capsule. Red cell debris and leucocytic debris are found
in spleen. There is an increase in the number of splenic macrophages (MACROPHAGES
In chronic cases, spleen becomes enlarged and fibrosed so much that it ruptures under the
influence of trauma. In chronic infections the spleen continues to enlarge (splenomegaly),
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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

becoming hard and blackened in color due to the accumulation of malaria pigment,

Relapse: In P. vivax and P.ovale malaria has the capacity to relapse, that is, there can be
a reappearance of parasites in the blood after the patient has been treated and seemingly
recovered. This type of relapse, called recurrence, is due to the delayed liberation of
merozoites from exo-erythrocytic schizonts in the liver, called hypnozoites. It may also
occur due to secondary exo-erythrocytic cycle.
Relapse commonly occurs between 824 weeks and is commonly seen with P. vivax and P.
ovale infections. It mainly occurs in temperate and tropical areas of Central and South
America, southern Asia and the Indian subcontinent. It accounts for about 45% of all
malaria cases. Parasites are often difficult to demonstrate in the peripheral blood film during

Value addition: Did you know?

Heading text: Recrudescence
Body text:
Recrudescence: Typically observed in P. falciparum and in P.malariae infection. It is
the renewed appearance of observable symptoms in the host due to persistence of
erythrocytic forms into the circulation.
After a number of paroxysms, primary attack subsides with the development of
partial immunity in the host. This is followed by a period of LATENCY during which
there is no clinical illness or sometimes-even PARASITAEMIA. The parasites are
not, however, eliminated at this stage, but persist in some erythrocytes, though the
level of parasitaemia is below the fever threshold, or even below the microscopic
threshold at times. Erythrocytic schizogony continues in the body at low levels and
gradually the number of parasites increases in number to cross the fever threshold.
Fresh malarial attacks then develop. These new malarial attacks that appear after a
period of latency, usually within 8 weeks after the culmination of primary attack, and
resulting from persistence of the erythrocytic cycle of the parasite are called
Recrudescence may be due to (1) Waning immunity of host, (2) Possibly to antigenic
variations in the parasite evading themselves from the immune responses of host (3)
An inadequate treatment with anti-malarial drugs. (4) Drug resistant persons There
may be several such recrudescenes, which are milder than the primary attack. After
varying number of such attacks, infection is eliminated in P. falciparum and P.
malariae infections.

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Malaria is endemic throughout most of the tropics and subtropics of the world. Out of the
approximately three billion people living in 106 countries who are exposed to malarial
parasite, approximately 243 million will develop symptomatic malaria annually.
P. vivax is most prevalent in 95 countries in tropical, sub-tropical and temperate
regions,(Guerra et al., 2009) except where there is a natural absence of anopheline
mosquitoes (east of Vanuatu in the South Pacific) or among populations lacking the Duffy
receptor on red cells (in much of Africa)(Baird 2008). It is only vivax malaria that occurs in
the temperate latitudes up to the Korean peninsula and across the southern temperate
latitudes of Asia to the Mediterranean Sea (Baird 2008).
Approximately 2.6 billion people are at risk of infection with P. vivax malaria, and the ten
a.( Guerra et al., 2009; Baird 2008) Estimates of annual infections range from 70 to 390
million, with about 80% occurring in South and Southeast Asia.( Baird 2008; Price et al.,
2007) Approximately 10-20% of the world's cases of P. vivax infection occur in Africa, south
of the Sahara.(Price et al., 2007) In eastern and southern Africa, 10% of malaria cases are
due to P. vivax, whereas it accounts for <1% of cases in western and central Africa.( Mendis
et al., 2001) Outside of Africa, P. vivax accounts for >50% of all malaria cases and about
80-90% of P. vivax outside of Africa occurs in the Middle East, Asia, and the Western Pacific
and 10-15% in Central and South America.( Mendis et al., 2001).

Value addition: Did you know?

Heading text: Malaria Endemicity
Body text:

Holoendemic: transmission occurs all year long

Hyperendemic: intense, but with periods of no transmission during dry season.
Mesoendemic: regular seasonal transmission
Hypoendemic: very intermittent transmission.

Source: ocw.jhsph.edu/courses/malariology/PDFs/lecture3.pdf

Mode of transmission
Infective stage

Sporozoites produced by sporogony in gut of female Anopheles mosquito.

Merozoites produced by schizogony in humans.

Source of infection
Sporozoites are introduced into the vertebrate host during the blood meal of infected female
Anopheles mosquito.

Transmission ways

The bite of a female Anopheles spp mosquito, which occurs mainly between dusk and
dawn introduces the parasite in human leading to malaria.
Congenital malaria caused by transmission of erythrocytic asexual forms of parasite
to foetus via placenta (rare mechanism mainly found in endemic areas).
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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Transfusion malaria occurs by blood transfusion, sharing of contaminated needles,

and organ transplant.

Factors Affecting Transmission

Distribution and abundance of the mosquito vector.

Temperature and extent of water for larval breeding.
Seasonal fluctuation of mosquito populations.
Duration of conditions suitable for mosquito survival

Susceptible population
Susceptible populations are the ones with no or little immunity against the disease. In areas
with high transmission (such as Africa south of the Sahara), the most vulnerable groups

Young children, who are yet to develop immunity to malarial parasite.

Pregnant women with decreased immunity.
Travelers or migrants from areas free from malaria.
In areas with lower transmission (such as Latin America and Asia), residents are less
frequently infected hence with low immunity.

A. Treatment of infected individuals
Individuals infected with malarial parasite should be treated with appropriate anti-malarial
drugs (depending on the type of infection).

B. Vector control
1. Destruction of adult mosquitoes.
Adult mosquitoes can be most effectively combated in dwellings. The following methods
can be employed to kill them:
(a) KILLING BY HANDS. The mosquitoes, which approach or bite, may be killed by hands
to save one as well as others.
(b) TRAPS. These are small boxes made of wire gauze and internally lined by black
paper or cloth. The mosquitoes tend to enter the boxes and then can be killed by closing
(c) FUMIGATION. Mosquitoes can be driven out of the houses or killed by fumigation.
sulphur, pyrethrum, cresol, tarcamphor or other derivaties of naphtha are burnt to
produce poisonous fumes. Smoke of garlic is now considered to be effective in driving
the mosquitoes out.
(d) SPRAYING. Mosquitoes can be killed inside human dwellings by using mosquitobombs or by spraying DDT, flit, pyrethrum and other insecticides.
(e) STERILIZATION. Sterilization of mosquitoes is now being achieved in some parts of
the world, particularly Japan. This method is very effective in controlling mosquito
2. Source Reduction

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

It involves permanent destruction of mosquito breeding sites: Swampy areas,

marshes and stagnant waters, such as pools, ponds, pits and ditches must be
drained off as they are breeding places of mosquitoes. If possible, the breeding
grounds may be filled up with earth or stones, etc. Eliminating receptacles that hold
water, such as tincans, buckets, cisterns, barrels, etc., can largely control domestic
species. Bushes and shrubs should be cleared off. Open drains should be closed or
made underground. Removing or covering standing water in vessels and rain barrels
around houses.
Removing or changing water from air coolers.
3. Chemical larviciding

Oils may be applied to the water surface, suffocating the larvae and pupae.
Oil solutions or emulsions of DDT, DDD and benzene hexachloride are effective
larvicides. Dusts containing Paris green, DDT or BHC are effective in the control of
surface feeding Anopheles larvae. Larger bodies of water can be sprayed with these
poisonous substances by aeroplanes.
Extracts of aquatic weed Ceratophyllum demensum control mosquito larvae in ponds.
When tulsi (Oscimum sanctum) seeds are introduced in water they swell and the
mucilage coating attracts and traps the mosquito larvae, which eventually die.
Toxins from the bacterium Bacillus thuringiensis var. israelensis (Bti) can be applied
in the same way as chemical insecticides. They are very specific, affecting only
mosquitoes, black flies, and midges.
Insect growth regulators such as methroprene are specific to mosquitoes and can be
applied in the same way as chemical insecticides.
4. Biological control

Larvicidal fishes, like stickle-backs, minnows (Gambusia) and trouts, etc., ducks and
aquatic nymphs and adult insects like dragon-flies, which are natural enemies of
mosquito, may be introduced in ornamental fountains, ditches, ponds, lakes, canals,
tanks, etc. They feed upon mosquito larvae and pupae.
Potential biological control agents, such as fungi (e.g., Laegenidium giganteum) or
mermithid nematodes (e.g., Romanomermis culicivorax), parasitize and kill larval
mosquitoes but they are not efficient for mosquito control and are not widely used.

C. Prevention from mosquito bite

Wearing protective light-colored long clothes that cover as much of the skin as
Use of mosquito net or Insecticide-treated bed nets while sleeping.
Use of mosquito repellant. Use of anti-mosquito creams (repellents) on exposed
parts of the bod
Building houses on high grounds.
Screening of doors, windows and ventilators.

Treatment of vivax malaria

Blood infection stage: Chloroquine remains the treatment of choice for vivax

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Liver infection stage: At least a 14-day course of primaquine is required for the
radical treatment (elimination of hypnozoites) of P.vivax. Eradication of the liver
stages is achieved by giving primaquine, after checking the patients G6PD (lucose-6phosphate dehydrogenase deficiency) status to reduce the risk of haemolysis.
Chloroquine resistance vivax malaria: Amodiaquine, mefloquine and quinine are
effective in the treatment of chloroquine-resistant P.vivax malaria. ACTs based on
either amodiaquine, mefloquine or piperaquine, rather than monotherapy, are the
recommended treatment of choice. These may also be used for P. vivax malaria in
combination with primaquine for radical cure.

Value addition: Did you know?

Heading text: Classification of Antimalarial drugs
Body text:
The currently available antimalarials fall into 4 broad groups:
1. Quinoline-related: quinine, chloroquine, amodiaquine, halofantrine, mefloquine
and primaquine, as well as the newer aryl amino-alcohol, lumefantrine
2. Anti-fols : pyrimethamine proguanil or Lapudrine , chlorproguanil, trimethoprim
and dapsone
3. Ubiquinone analogs: atovaquone
4. Artemisinin compounds: artemisinin, artemether, arteether and artesunate
Anti-malarial drugs can be classified on the basis of type of action:
1. Suppressive - effective on asexual blood stages and limits clinical symptoms.
2. Therapeutic - effective on asexual blood stages in the acute stage.
3. Radical cure - effective on extra-erythrocytic forms.
4. Gametocidal - effective on the gametes.
5. Sporonticidal - effective on the sporozoites in the mosquito and makes them
noninfective to the vertebrate host.

Value addition: Did you know?

Heading text: The oldest yet least understood antimalarial drug!
Body text: Primaquine is one of the oldest of currently used anti-malarial drugs and
is the least well understood. This drug was first deployed to prevent P. vivax relapses in
US soldiers returning to the United States from World War II. Primaquine destroys the
liver forms of all plasmodium species but toxicity considerations preclude its widespread
use in the control of malaria. Primaquine can also precipitate acute and dangerous
intravascular haemolysis in subjects with glucose-6-phosphate dehydrogenase (G6PD)
deficiencies, who are most frequently found in malaria-endemic countries.
Source: http://www.nature.com/nrd/journal/v8/n11/images/nrd2960-f1.jpg

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax


There are three distinct asexual replicative stages of malaria parasites - exoerythrocytic
schizogony, blood stage schizogony, and sporogony, which results in the production of
invasive, forms -merozoites and sporozoites.

All invasive stages have apical organelles, which is typical characteristic of apicomplexan

Different invasive stages invade different types of cells or tissues and their motility also varies.

After the successful invasion of host, a few of these invasive forms show high multiplication to
establish the infection in the new host.

During the blood meal, sporozoites are injected with the saliva of a feeding mosquito into the
host thus initiating the infection.

The circulatory system of the host carries the sporozoites to the liver and where they invade

Within the hepatocyte, the intracellular parasite replicates asexually called exoerythrocytic

Exoerythrocytic schizogony results in the production of merozoites, which are released into the

In case of P. vivax, a proportion of the liver-stage parasites remain in a dormant period inside
the liver cells instead of immediately undergoing asexual replication. They are called

Hypnozoites, which are responsible for, relapses, reactivates after several weeks to months
(or years) after the primary infection. Merozoites invade erythrocytes and undergo a trophic
period in which the parasite enlarges.

Due to ring like appearance, the early trophozoite is often referred to as 'ring form'.

Trophozoite enlargement occurs by an active metabolism inside host cell, which includes the
ingestion of host cytoplasm and the proteolysis of hemoglobin into amino acids.

A schizont is formed at the end of the trophic period by multiple rounds of nuclear division
without cytokinesis.

Merozoites also called a segmenter bud out of the mature schizont, which are then released
following rupture of the infected erythrocyte.
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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

These merozoites now enter fresh erythrocytes thus reinitiates another round of the bloodstage replicative cycle.

Periodic onset of fevers in malaria is due to the synchronous rupture of infected erythrocytes
and release of merozoites.

The parasite can also differentiate into sexual forms known as macro- or microgametocytes
instead of undergoing asexual replicative cycle.

A sexual reproduction occurs as the parasite switches from vertebrate to invertebrate host
resulting in invasive ookinete.

Ingestion of gametocytes by the mosquito vector sets in gametogenesis (i.e., the production of
gametes) thus they escape from the host erythrocyte.

A drop in temperature, an increase in carbon dioxide, and mosquito metabolites may induce

Microgametes are flagellated forms, formed by the process of exflagellation, which fertilizes
the macrogamete leading to the formation of a zygote.

The zygote develops into a motile ookinete, which penetrates the gut epithelial cells of
mosquito and develops into an oocyst.

Multiple rounds of asexual replication of the oocyst results in the production of sporozoites.

Sporozoites are released into the hemocoel (body cavity) of the mosquito by rupturing of the
mature oocyst. The sporozoites then migrate to and invade the salivary glands of the
mosquito, thus completing the life cycle.

Summary of prevention and control:

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Fig. 17.Summarized steps for control of Malaria

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

1. Fill in the Blanks:
a. Malaria is caused by a protozoan of the genus ___________ and requires two hosts,
________ and ________, to complete its life cycle.
b. The infective stage of Plasmodium is ____________.
c. The replication of the sporozoite within the hepatocyte is called ___________.
d. The male and female gametocytes of Plasmodium are known as ____________ and
__________ respectively.
e. __________ are introduced into the vertebrate host during the blood meal of infected
female Anopheles mosquito.

A person is infected with Plasmodium vivax undergoes chills and fever about every
________ hours. This event corresponds to the ________.

2. Very short answer type questions:

a. Name the disease caused by Plasmodium.
b. Name the different species of Plasmodium hosted by man.
c. Name the vector associated with the transmission of the disease caused by the
organism Plasmodium in human beings.
d. Name the definitive and intermediate host for the parasite Plasmodium, to complete its
life cycle.
e. Name the seven species of Anopheles mosquito found to cause malaria in humans in

Name the different vertebrate host of malarial parasite.

g. Name the cells where you can find the ring trophozoite form of Plasmodium in people
infected with malaria.
3. Differentiate between:

Definitive and intermediate host

Sporozoite and merozoite
Erythrocytic schizogony and exoerythrocytic schizogony
Gametogenesis and gametocytogenesis
Relapse and Recrudescence

4. Briefly describe the characteristic features of various morphological forms of Plasmodium.

5. Describe the salient features of life cycle of Plasmodium that takes place in human.
6. Describe the sporogonic cycle of malarial parasite.
7. Draw a labeled diagram of lifecycle of malarial parasite.
8. Briefly describe malarial paroxysm.
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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

9. Briefly describe the prophylaxis for malaria.
10. Describe the main clinical manifestations of malaria.
11. Describe the salient features of erythrocytic schizogony.
12. What are various transmission ways for malaria? Describe the factors affecting the
transmission of malaria.

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Definitive host: The host harbouring either the adult stage of the parasite or the parasite
reproduces sexually.
Erythrocyte: A red blood cell.
Erythrocytic stage: As the malarial parasites are found in the red blood cells, it is called
erythrocytic stage. It causes the symptoms of malaria in the host.
Exoerythrocytic stage: Exoerythrocytic stage malarial parasites are found in liver cells
(hepatocytes) and they do not cause symptoms.
Gametocyte: Gametocyte is the sexual stage of malaria parasites. Male gametocytes
(microgametocytes) and female gametocytes (macrogametocytes) are inside red blood cells in
the circulation.
Gametocytogenesis: The process of differentiation of gametocytes in the red blood cells of
humans is called gametocytogenesis.
Hepatocytes: Liver cells.
Hypnozoite: Dormant form of malaria parasites, found in liver
with Plasmodium vivax and P. ovale. After sporozoites invade
develop into dormant forms (the hypnozoites), which do
Hypnozoites can become activated months or years after the

cells. Hypnozoites occur only

liver cells, some sporozoites
not cause any symptoms.
initial infection, producing a

Incubation period: It is the time gap between the introduction of malarial parasites in the
host by mosquito bite and the first appearance of clinical symptoms.
Intermediate host: The host harbouring the juvenile stages of the parasite or where the
parasite divides asexually.
Merozoite: Asexually produced daughter cell in the life cycle of malarial parasites. Schizonts
developed from liver-stage and blood-stage malarial parasites contain many merozoites, which
are released when the schizonts mature and rupture.
Oocyst: Oocysts are rounded structures located in the outer wall of the stomach of
mosquitoes. Inside the oocysts, the infective stage of malarial parasite develops which are
released when oocysts mature and rupture.
Parasitaemia: It is a condition in which parasites are present in the blood
Prepatent period: It is defined the time gap between the introduction of malarial parasites in
the host by mosquito bite and the first appearance of the trophozoites in erythrocytes.
Relapse: Typically observed in P.vivax and P.ovale infection, when treated with drugs that are
ineffective on the parasitic liver stages. It is a renewed appearance of clinical symptoms due to
exo-erythocytic cycle started by persistent liver merozoites (hypnozoites) months after the
invasion of the hepatocyte.

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Life Cycle, Pathogenicity and Prophylaxis of Plasmodium vivax

Schizogony: Asexual reproductive stage of malarial parasites. Schizogony causes
development of a single trophozoite into numerous merozoites in erythrocytes and infected
Schizont: A developmental form of the malarial parasite containing many merozoites. They
are seen in the liver and blood parasitic stage.
Sporozoite: It is the infective stage in the life cycle of the malarial parasites that are
produced in the mosquitos gut and migrate to the mosquito's salivary glands. They can be
transmitted during blood meal on the human.
Trophozoite: A developmental form during the blood stage of malaria parasites developed
from merozites, which invade the red blood cell.
Vector: An organism that transmits an infectious agent from one host to the other.

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Works Cited
Krotoski WA.( 1985) Discovery of the hypnozoite and a new theory of malarial relapse. Trans R
Soc Trop Med Hyg.,79: 1-11
Paniker, C.K. J., Textbook of Medical Parasitology, 6th edition, 2007.
Guerra CA, Howes RE, Patil AP, Gething PW, Van Boeckel TP, et al. The International Limits and
Population at Risk of Plasmodium vivax Transmission in 2009. PLoS Negl Trop Dis. 2010; 4(8):
e774. doi: 10.1371/journal.pntd.0000774
Baird JK. Real-World Therapies and the Problem of Vivax Malaria. N Engl J Med 2008;359:26012603. Available at http://www.nejm.org/doi/full/10.1056/NEJMe0808729#t=article
Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, Anstey NM. Vivax malaria: neglected and not
benign. Am J Trop Med Hyg 2007;77:79-87.
Mendis K, Sina BJ, Marchesini P, Carter R. The neglected burden of Plasmodium vivax malaria.
Am J Trop Med Hyg 2001;64(1):suppl 97-106. Available at

Suggested Readings
Ahmed,N., Dawson, M., Smith, C and Wood, Ed.,(2007) Biology of Disease. Published by
Taylor and Francis Group
Chatterjee, K. D., Parasitology in relation to clinical medicine
Kreier, J.P. and Baker, J.R. Parasitic Protozoa.Allen and Unwin publishers ltd.
Paniker, C.K. J., Textbook of Medical Parasitology, 6th edition, 2007.
Smyth, J.D., (2004) Animal Parasitology, 3rd edition . Cambridge University Press.
Ruppert, Fox and Barnes (2006) Invertebrate Zoology. A Functional Evolutionary Approach 7th
edition. Thomson Books/ Cole.

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