MALARIA Assignment on BCH 514 Clinical Biochemistry - Description
Submitted by Selma Abdul Samad BCH100502 S3 MScBiochemistry What is Malaria An infectious tropical Disease caused by the parasite Plasmodium sp in humans The name malaria derived from the Italian ID: 775355 Download Presentation
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Resistance of mosquitoes to insecticide and increasing prevalence of chloroquine resistance has led to an increase in complicated malaria in different part s of India Malaria especially falciparum malaria can cause various complications involving va
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MALARIA Assignment on BCH 514 Clinical Biochemistry
Submitted by. Selma Abdul . Samad. BCH-10-05-02. S3 . MSc.Biochemistry. What is Malaria ??. An infectious tropical Disease caused by the parasite Plasmodium sp. in . humans. The name malaria derived from the Italian .
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MALARIA Assignment on BCH 514 Clinical Biochemistry
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BCH 514 Clinical Biochemistry
What is Malaria ??
An infectious tropical Disease caused by the parasite Plasmodium sp. in
The name malaria derived from the Italian
Fifth cause of death from infectious diseases worldwide (after respiratory infections, HIV/AIDS, diarrhoeal diseases, and tuberculosis) and the second in Africa, after HIV/AIDS
It is a disease that can be treated in just 48 hours, yet it can cause fatal complications if the diagnosis and treatment are delayed.
#1 priority tropical disease of WHO
Prevalent in 108 countries of the tropical and semitropical world (
home to half of the world
Every year, malaria is reported to cause more than 250-660 million infections and more than a million deaths (
mostly among African children
There has been a sharp decline in the incidence of malaria in South-East Asia since 1977 reflecting a rapid fall in India and Sri Lanka but . there has been a slow increase in South and Central America.
In India ..
Orissa, Chhattisgarh, West Bengal, Jharkhand and Karnataka contribute the most number of cases of malaria in India
HISTORY OF MALARIA
One of the oldest diseases known to mankind
Wars , kings , dynasties etc influenced
Malaria was linked with poisonous vapours of swamps or stagnant water on the ground since time immemorial.
The word was introduced to English by Horace Walpole, who wrote in 1740 about a “horrid thing called
, that comes to Rome every summer and kills one.” The term malaria, without the apostrophe, evolved into the name of the disease only in the 20th . century.
Man and Malaria seem to have evolved together
It is believed that most, if not all, of today's populations of human malaria may have had their origin in West Africa (P.
) and West and Central Africa (P.
) on the basis of the presence of homozygous alleles for
C and RBC Duffy negativity that confer protection against P.
Different studies have suggested that P.
malaria probably jumped from great apes to man, probably by a single host transfer by vector mosquitoes
, and P.
diverged over 100 million years ago along the lineage of the mammalian malaria parasites
sole known surviving representative of its line and causes infection only in humans
Famous victims of malaria
Alexander the Great is believed to have died of malaria in 323 BC, on the route to India beyond MesopotamiaGeorge Washington, (1st President of US, 1789-1797): Developed his first bout with malaria in Virginia in 1749 at age 17. He had periodic attacks, recorded in 1752, 1761, 1784, and 1798.Abraham Lincoln (16th President, 1861-1865) had periodic bouts of malaria when growing upJohn F. Kennedy (35th President, 1961-1963) acquired malaria during World War II, about 1943Mother Teresa was hospitalized with malaria in 1993, ……………….and many many others………………..
Hippocrates was probably the the first malariologist The Hippocratic corpus was the first document to mention about splenic change in malaria and also it attributed malaria to ingestion of stagnant water
Time Line For Scientific Discoveries
Ancient Times - Early man attributed the fevers to evil spirits, angered deities, demons, or the black magic of sorcerers
thousand years ago - Babylonian cuneiform script attributes malaria to a god, pictured as a mosquito-like insect
800 BC - Indian sage
wrote that bites of mosquitoes could causes diseases, fever, shivering etc.
400 BC - Hippocrates described the various malaria fevers of man; distinguished the intermittent malarial fever from the other continuous fevers; noted the daily, every-other-day, and every-third-day temperature rise; mentioned about
change in malaria; attributed malaria to ingestion of stagnant water; also related the fever to the time of the year and to where the patients lived
Several theories and hypotheses came for years
It was finally in 1884 that Plasmodium was discovered by Russian Scientists and their link with malaria was confirmed by Louis Pasteur.In 1897 Ronald Ross demonstrated oocysts in the gut of anopheline mosquito at Secunderabad, India, proving that mosquito was the vector for malaria
Nobel Prizes for Malaria Related Research
Ronald Ross, 1902: "For his work on malaria, by which he has shown how it enters the organism and thereby has laid the foundation for successful research on this disease and methods of combating it". Ronald Ross demonstrated the oocyst of malarial parasite in the gut wall of a mosquito on August 20, 1897 in Secunderabad, India.Alphonse Laveran, 1907: "In recognition of his work on the role played by protozoa in causing diseases". Laveran was the first to notice parasites in the blood of a patient suffering from malaria on November 6, 1880 at Constantine, Algeria.
Jauregg, 1927: "For his discovery of the therapeutic value of malaria inoculation in the treatment of dementia paralytica".Paul Hermann Müller, 1948: "For his discovery of the high efficiency of DDT as a contact poison against several arthropods".
5 species of malaria parasites that infect man identified
Principal mode of spread of malaria is by the bites of female
Of more than 480 species
, only about 50 species transmit malaria
The habits of most of the
mosquitoes have been characterised as
(prefer human blood meal),
(bite indoors), and nocturnal (bite at night) with peak biting at midnight, between 11 pm and 2 am.
The blood meal from a vertebrate host is essential for the female mosquitoes to nourish their eggs.
The mosquitoes find their host by seeking visual, thermal, and olfactory stimuli and of these, carbon dioxide, lactic acid, skin temperature, and moisture are more important mosquito attractantsWhen a mosquito bites an infected individual, it sucks the gametocytes, the sexual forms of the parasite, along with blood. These gametocytes continue the sexual phase of the cycle within the mosquito gut and the sporozoites that develop then fill the salivary glands of the infested mosquito. When this female mosquito bites another man for a blood meal, the sporozoites are inoculated into the blood stream of the fresh victim, thus spreading the infection.
Malaria is transmitted from man to man by the female anopheles mosquito
Nearly 45 species of the mosquito have been found in IndiaHow does a mosquito bite?
Other modes of transmission
Mother to the growing
(Congenital malaria) -
transmitted by transfusion of blood from infected donors.
Needle stick injury:
accidentally among health care or due to needle sharing among drug addicts
The malaria parasite has a complex, multistage life cycle occurring within two living beings, the vector mosquitoes and the vertebrate hosts.
of two phases
Sexual phase (
) – in female anopheles mosquito
Asexual phase (
) – in man
The parasite passes through several stages of development such as the
= seeds; the infectious form injected by the mosquito)
= piece; the stage invading the erythrocytes)
= nourishment; the form multiplying in erythrocytes) and
gametocytes (sexual stages)
all these stages have their own unique shapes and structures and protein complements.
The surface proteins and metabolic pathways keep changing during these different stages, that help the parasite to evade the immune clearance, while also creating problems for the development of drugs and vaccines
Sporogony Within the Mosquitoes
Mosquitoes are the definitive hosts for the malaria parasites, wherein the sexual phase(
) of the parasite's life cycle occurs
Results in the development of innumerable infecting forms of the parasite within the mosquito that induce disease in the human host following their injection with the mosquito bite
mosquito draws blood
the male and female gametocytes of the parasite find their way into the gut of the mosquito
; Males form microgamete
The male and female gametes fuse in the mosquito gut to form zygotes, which subsequently develop into actively moving
that burrow into the mosquito
wall to develop into
Growth and division of each
produces thousands of active haploid forms called
phase of 8–15 days, the
bursts and releases
into the body cavity of the mosquito, from where they travel to and invade the mosquito salivary glands.
When the mosquito thus loaded with
takes another blood meal, the
get injected from its salivary glands into the human bloodstream, causing malaria infection in the human host.
It has been found that the infected mosquito and the parasite mutually benefit each other and thereby promote transmission of the infection. The
-infected mosquitoes have a better survival and show an increased rate of blood-feeding, particularly from an infected host.
The duration of the cycle in the mosquito is known as the external incubation period and varies from 8-10 days (28`C) to 16 days (20`C)
on stomach of mosquito
Schizogony in the Human Host
Man is the intermediate host for malaria, wherein the asexual phase of the life cycle occurs.
inoculated by the infested mosquito initiate this phase of the cycle from the liver, and the latter part continues within the red blood cells, which results in the various clinical manifestations of the disease.
in the Liver:
With the mosquito bite, tens to a few hundred invasive
are introduced into the skin.
are destroyed by the local macrophages, some enter the
, and some others find a blood vessel.
that enter a lymphatic vessel reach the draining lymph node wherein some of the
partially develop into
stages and may also prime the T cells to mount a protective immune response
that find a blood vessel reach the liver within a few hours
then negotiate through the liver sinusoids, and migrate into a few
, and then multiply and grow within
develop into a
(or more in case of
The growth and development of the parasite in the liver cells is facilitated by a
environment created by the
protein of the parasite.
The entire pre-
phase lasts about 5–16 days depending on the parasite species:
on an average 5-6 days for
9 days for
13 days for
8-9 days for
phase remains a “silent” phase, with little pathology and no symptoms, as only a few
are affected. This phase is also a single cycle, unlike the next,
stage, which occurs repeatedly.
that develop within the
are contained inside host cell-derived vesicles called
that exit the liver intact, thereby protecting the
are eventually released into the blood stream at the lung capillaries and initiate the blood stage of infection thereon.
malaria, some of the
may remain dormant for months within the liver. Termed as
, these forms develop into
after some latent period, usually of a few weeks to months.
- Centre Stage in Red Cells
Red blood cells are the 'centre stage' for the asexual development of the malaria parasite.
Within the red cells, repeated cycles of parasitic development occur with precise periodicity, and at the end of each cycle, hundreds of fresh daughter parasites are released that invade more number of red cells.
released from the liver recognize, attach, and enter the red blood cells (RBCs) by multiple receptor–
interactions in as little as 60 seconds. This quick disappearance from the circulation into the red cells minimises the exposure of the antigens on the surface of the parasite, thereby . protecting these parasite forms from the host immune response.
The invasion of the
into the red cells is facilitated by molecular interactions between distinct
and host receptors on the erythrocyte membrane.
, the major
glycoprotein is involved in
The more virulent
uses several different receptor families and alternate invasion pathways that are highly redundant and hence can invade any red cell while others like
can invade using one type of receptor.
The process of attachment, invasion, and establishment of the
into the red cell is made possible by the specialized apical
organelles of the
, called the
, and dense granules.
The initial interaction between the parasite and the red cell stimulates a rapid “wave” of deformation across the red cell membrane, leading to the formation of a stable parasite–host cell junction.
Following this, the parasite pushes its way through the erythrocyte
with the help of the
–myosin motor, proteins of the
-related anonymous protein family (TRAP) and
, and creates a
vacuole to seal itself from the host-cell cytoplasm, thus creating a hospitable environment for its development within the red cell.
At this stage, the parasite appears as an intracellular “ring”.
The ring forms grow in size to
. Meanwhile, they
., the amino acids are
and the toxic
is detoxified by
polymerase and sequestered as
The parasite depends on anaerobic
dividing into a number of small
varying with the species to form a mature
phase is called
At the end of the
are released by rupture of the red cell membrane and enter new red cells, particularly young red cells.
cycle occurs every
24 hours in case of
48 h in cases of
72 h in case of
During each cycle, each
grows and divides within the vacuole into 8–32 (average 10) fresh
, through the stages of ring,
A small proportion of asexual parasites do not undergo
but differentiate into the sexual stage gametocytes.
These male or female gametocytes are extracellular and
and help in transmission of the infection to others through the female
mosquitoes, wherein they continue the sexual phase of the parasite's life cycle.
develop soon after the release of
from the liver, whereas in case of
, the gametocytes develop much later with peak densities of the sexual stages typically occurring 1 week after peak asexual stage densities.
The most pronounced changes related to malaria involve the blood and the blood-forming system, the spleen and the liver.
Secondary changes can occur in all the other major organs, depending on the type and severity of the infection.
The pathological changes are more profound and severe in case of
malaria. Severe malaria is a complex multisystem disorder with many similarities to sepsis syndromes.
RBC rupture ;
Thrombocytopenia ; Clotting defects
Bone marrow may show evidence of
, iron sequestration and
in the acute phase of
Malarial hepatitis ;
cardiovascular function abnormalities
GI irritation, ischemia, ulcers , necrosis
; kidney failure ; edema
CNS manifestations ( in
All pathological manifestations increased and severe in case of
All the clinical features of malaria are caused by the
in the blood
It includes three stages viz. Cold stage, Hot stage and Sweating stage
The febrile episode starts with shaking chills, usually at mid-day between 11 a.m. to 12 noon, and this lasts from 15 minutes to 1 hour (the cold stage)
Followed by high grade fever, even reaching above 106
F, which lasts 2 to 6 hours (the hot stage).
This is followed by profuse sweating and the fever gradually subsides over 2-4 hours. These typical features are seen after the infection gets established for about a week.
malaria, this typical pattern of fever recurs once every 48 hours and this is called as
Benign Tertian malaria.
Similar pattern may be seen in
this pattern may not be seen often and the paroxysms tend to be more frequent
infection, the relapses occur once every 72 hours and it is called
In an endemic area, malaria often presents with atypical manifestations
Body ache, back ache and joint pains
Altered behaviour, acute psychosis
Vomiting and diarrhoea
Puffiness of lids
Combinations of the above
Clinical features suggesting
Presence of any of the complications of
malaria viz. altered
; convulsions; coma; jaundice; severe
; hypotension; prostration; hyperpyrexia; renal failure etc.
Not responding to
therapy within 48 hours
Recurrence within 2 weeks
Involves identification of malaria parasite or its antigens/products in the blood of the patient
The efficacy of the diagnosis is subject to many factors
The different forms of the four malaria species;
The different stages of
of different species;
The inter-relation between the levels of transmission, immunity,
, and the symptom
The problems of recurrent malaria, drug resistance, persisting viable or non-viable
The diagnosis of malaria is confirmed by blood tests and can be divided into
The microscopic tests involve staining and direct visualization of the parasite under the microscope.
1. Peripheral smear study
2. Quantitative Buffy Coat (QBC) test
- Rapid Diagnostic tests , PCR assays ,
for detection of plasmodia , ELISA for malaria antigens , Western blotting etc.
Malaria can be offered as a differential diagnosis for a big list of diseases.
All other causes of fever, migraine, sinusitis, tension headache etc.