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EPIDEMIOLOGY AND PATHOLOGY OF MALARIA
OBJECTIVES
At the end of the session the student should be able to:
Define Malaria and list the types of plasmodium species causing malaria
Describe the pathogenesis with relevant lab tests
PARASITE CAUSING MALARIA
Parasites causing malaria belong to the class coccidia and genus ‘plasmodium’
Plasmodium is classified as follows:
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P.falciparum: (most deadly)Causes malignant tertian fever
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P.vivax: Causes benign tertian fever
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P.malariae: Causes quartan fever
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P.Ovale: Causes ovale tertian fever
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GEOGRAPHICAL DISTRIBUTION
Malaria is the most clinically important and widespread parasitic infection. It is
prevalent in developing tropical countries.
P.falciparum is found mainly in hot and humid climate. It is the main species found
in tropical and subtropical Africa, Bangladesh, Pakistan, Afghanistan, Nepal, Sri
Lanka, South East Asia, Indonesia, Philippines, Papua New Guinea and many
parts of India.
LIFE CYCLE IN MAN
When a female Anopheles mosquito bites a human being it injects the parasite in
the form of ‘Sporozoites’
while taking the blood meal.
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PRE-ERYTHROCYTIC SCHIZOGONY
The sporozoites enter the liver cells. These are thread like curved parasites
with tapering ends, and an elongated nucleus. Inside the hepatocytes the
sporozoites develop into ‘Merozoites’. In P. falciparum preerythrocyticSchizogony completes in 6 days, in P. Ovale, 9 days, in P. Vivax 8
days and in P. Malariae 15 days.
Merozoites are liberated as the hepatocytes filled with the parasites rupture.
The liberated parasites attack red blood cells. (The blood remains sterile
during pre-erythrocytic stage and there are no clinical manifestations or
pathological damage).
ERYTHROCYTIC SCHIZOGONY
During this stage, the parasites invade the RBC
TROPHOZOITES
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It looks like a blue cytoplasmic ring like structure with a red nuclear mass and an
unstained area the ‘nutrient vacuole’.
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This form shows active amoeboid movements, and is active metabolically.
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After some time pigment granules start to appear, which represent
metabolic products of the parasite.
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In P. falciparum infection, the trophozoite is attached to the periphery of the
host red blood cell. The pigment granules are dark brown or black in colour
known as Maurer’s dots
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In P. vivax, the RBC becomes distorted and double of its original size. The
pigments resemble basophillic stippling are yellow or brown in colour and
known as Schuffner’s dots
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In P. Malariae, the trophozoite stretches like a band across the infected RBC.
Pigment granules are coarse, black and known as Ziemanon’s dots
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SCHIZONT
Schizont is a fully grown trophozoite.
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In P. falciparum the nucleus of schizont divides several times and forms round
masses called merozoites.
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In P. Vivax the merozoites formed from schizont are arranged in a rosette form,
with the pigmented mass in the centre.
SCHIZONT: HEPATIC STAGE
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EXOERYTHROCYTIC SCHIZOGONY
After establishment of blood infection the pre erythrocytic phase disappears
completely in P. falciparum.
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But in P. Vivax, P. Ovale and P. malariae, it persists in the form of local schizogony
in the liver.
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This is responsible for the relapses in these species. The merozoites liberated in
this schizogony are called ‘Hypnozoites’.
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LIFE CYCLE IN MOSQUITO
The sexual cycle starts in the human host with the formation of ‘Gametocytes’,
which further develop inside the female anopheles mosquito.
Only the mature sexual forms develop inside the mosquito.
In order to infect the mosquito the human blood per mm3 must contain at least 12
and the number of female gametocytes should be in excess.
From one micro gametocyte (male gametocyte) 5-8 microgametes are developed
in the mid-gut. This is called ‘Ex-flagellation’.
ZYGOTE
The macrogametocyte (female) gives rise to only one macrogamete.
Fusion of male and female gametes results in the formation of a ‘Zygote’.
The Zygote is converted into ‘Ookinite’ which further develops into ‘Oocyst’, inside
the gut cells of mosquito.
SPOROZOITES
The oocyte matures and forms a large number of Sporozoites.
On the 10th day of infection the oocyte ruptures liberating sporozoites in the body
cavity of mosquito.
The sporozoites migrate towards the salivary glands where they concentrate in the
ducts.
At this stage the mosquito is able to transmit the infection to man. A single bite of
mosquito is sufficient for this purpose.
INFECTION
Different species of plasmodium can develop in the same mosquito and it can
transmit ‘mixed’ type of infection. The most common combination is that of P.
falciparum and P. Vivax.
Infection with plasmodium causes intermittent fever known as ‘Malaria’. The word
is derived from two Latin words ‘mala (bad) and aria (air).
Marshy places are the most suitable breeding sites for mosquitos.
STAGES OF MALARIA
Cold Stage – Characterized by rigors and headache. Patient feels cold and
shivers. This condition occurs due to release of toxic metabolites from the
ruptured RBC in the blood, after erythrocyticschizogony.
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Hot Stage – During this stage the temperature rises to maximum with severe
headache. There is pain in joints and back ache associated with vomiting.
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Wet Stage – During this stage the patient perspires, temperature falls and pain
is relieved until the next attack.
SYMPTOMS
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Fever
Chills
Sweating
Headaches
Muscle pains
Severe complications:
Cerebral malaria
Anemia
Kidney failure
Severe complications can result in death.
FEVER
In P. falciparum attacks of fever recur on alternate days. The fever may be
continuous or be irregular.
In P. vivaxfever recurs after 48 hours. Relapses are a feature of P. vivax infection.
They may occur 8-10 weeks after a previous attack or even about 30-40 weeks
later.
In P. ovalethe fever recurs after 48-50 hours. There are fewer relapses as
compared to P. vivax.
In P. malariaeinfection, malarial attack occurs regularly about every 72 hours.
ANAEMIA
After a few paroxysms, a microcytic or normocytic, normochromic anemia develops
as a result of breaking of RBC.
Changes on the surface of parasitized RBC cause cells to adhere to one another
and to the cells lining the walls of capillaries.
This results in sequestration of infected RBC, in the capillaries of internal organs.
It leads to congestion, hypoxia, blockage and sometimes rupture of small blood
vessels
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CEREBRAL MALARIA
This is usually a fatal and a serious complication of falciparum malaria.
This occurs due to blockage of blood capillaries and venules in the brain, by the
parasitized RBC and fibrin.
The major life threatening complications of P.falciparum in African children are
cerebral malaria and anemia associated with metabolic acidosis and respiratory
distress.
BLACK WATER FEVER
This is another complication of falciparum malaria.
It is a rare but acute condition, in which massive intravascular haemolysis of
parasitized RBCs occurs.
It results in severe haemoglobinuria, and fall in haemoglobin.
Urine appears brown to black (hence the name Black water fever).
It is accompanied by high fever, vomiting jaundice and is often fatal due to renal
failure.
Probably Black water fever occurs as a result of an autoimmune factor in the host
which develops after repeated attacks of falciparum malaria.
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SPLENOMEGALY: Splenomegaly is one of the important physical signs and
complications. Spleen acts as a filter to remove the parasites and their toxic
metabolites, from the blood stream.
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PERNICIOUS MALARIA: Pernicious malaria is a condition which occurs in severe
falciparum infection and the condition threatens the life of the patient within 1-3
days.
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ALGID MALARIA: This occurs due to severe dehydration and haemorrhagic
shock due to splenic rupture. The patient becomes susceptible to bacterial
infections due to a transient immuno-suppression.
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NEEDLE STICK MALARIA: This is transfusion malaria which is transmitted to the
recipient from an infected blood donor.
RELAPSES
Relapses are a common feature of malaria caused by P. vivax and probably in
ovale and malariae also.
Due to inadequate drug therapy, resistance develops along with the patient’s
reduced natural acquired immunity e.g. during pregnancy.
Relapses occur due to delayed development of parasites in the liver. These forms
are termed as ‘Hypnozoites’
RECRUDESCENCE
Relapse does not occur in P. falciparum but a condition termed as
‘Recrudescence’ may occur which results from persistence of blood parasites.
In falciparum species there is no true relapse as there is no hypnozoite stage in
this species.
BLOOD STAINING
This is done by staining thin and thick blood films of peripheral blood.
Thick film is useful for rapid detection of parasites
Thin film is used to see the morphology and species can also be identified.
P. Falciparum infection:
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Trophozoites and gametocytes are seen in the peripheral blood film, as
erythrocyticschizogony takes place in the internal organs only.
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If Schizonts are seen, it indicates a heavy parasitaemia and a serious falciparum
infection.
P. Ovale infection:
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Young RBCs are more affected.
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Trophozoites, schizonts and gametocytes can be seen.
P. Vivax infection:
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Rarely more than 2% RBC become infected and young cells are preferentially
parasitized.
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Trophozoites, schizonts and gametocytes can be seen on a peripheral blood film.
P. Malariae infection:
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less than 1% RBCs are infected. Parasitaemia is lowest as compared to other
species.
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Trophozoites, schizonts and gametocytes can be detected on peripheral blood film.
GAMETOCYTE
SEROLOGICAL TESTS
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Complement fixation test.
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Becton – Dickinson’s QBC method (Quantative buffy coat) is effective. In this
method blood is spun in small capillaries in which parasite DNA is stained with
acridine orange and the RBC are examined by ultraviolet microscopy.
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Immunofluorescent test.
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DNA probes using PCR (Polymerase chain reaction) and chemo- luminescence for
detection are useful to detect infection as well as parasite species.
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A rapid test is also designed in which dipstick method is used to detect antigen by
a monoclonal antibody against histidine rich protein antigen of P. falciparum.
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Passive haemagglutination test.
BLOOD PHASE: RINGS
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