Malaria pdf - د. إكرام الحسو

Parasitology

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Malaria Lec.3

Pathogenesis and Clinical Features

Clinical manifestations in malaria are caused by products of erythrocytic schizogony and

the host's reaction to them.

 The disease process in malaria occurs due to:

the local or systemic response of the host to parasite antigens.

II.

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

flow by the parasitized erythrocytes.

 Liver is enlarged and congested. Kupffer cells are

increased and filled with parasites.

 Spleen is soft, moderately enlarged and congested

in acute infection. In chronic cases, spleen is hard.

  Kidneys are enlarged and congested.
  The brain in P. falciparum infection is congested.
  Anemia: After few paroxysms of fever, normocytic

and normochromic anemia develops.

Clinical Features of Benign Malaria

 It is characterized by a triad of febrile paroxysm, anemia and splenomegaly.

Febrile paroxysm

❖ Fever comes intermittently depending on the species. It occurs every fourth day (72

hour cycle for P. malariae) and every third day (48 hour cycle for other three

species)

 Paroxysm corresponds to the release of the successive broods of merozoites into

the bloodstream, at the end of RBC cycle.

 The paroxysm usually begins in the early afternoon and lasts for 8-12 hours.
❖ Each paroxysm of fever is

comprised of three stages:

1. Cold stage: The patient feels intense cold with chill and rigor along with lassitude,

headache and nausea. This stage lasts for 15 minutes to 1 hour.

2. Hot stage: The patient feels intensely hot. The temperature mounts to 39

–41 °C or

higher. Headache persists but nausea commonly diminishes. This stage lasts for

2-6 hours.

3. Sweating stage: Fever comes down with profuse sweating. Skin becomes cold

and moist. Patient feels relieved and often asleep. This stage lasts for 2

–4 hours.

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Parasitology

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Anemia

 After a few paroxysms of fever,the patient develops a normocytic

normochromic anemia. Various factors can attribute to the development of

anemia such as:

1. Parasite induced RBC destruction

—Lysis of RBC due to release of merozoites.

2. Splenic removal of both infected RBC and uninfected RBC coated with immune

complexes.

3. Bone marrow suppression leading to decrease RBC production.

4. Increased fragility of RBCs.

5. Autoimmune lysis of coated RBCs.

Splenomegaly

 After a few weeks of febrile paroxysms, spleen gets enlarged and becomes

palpable. Splenomegaly is due to massive proliferation of macrophages that engulf

parasitized and non-parasitized coated RBCs.

Clinical Features of Malignant Tertian Malaria

 The most serious and fatal type of malaria is malignant tertian malaria caused by

P. falciparum. Falciparum malaria

if not treated timely or adequately, severe life-

threatening

complications may develop. In severe falciparum malaria, parasitic load

is very high. it invades erythrocytes of all ages (old and young).

Parasitology

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. Cerebral malaria:

 Occurs due to plugging of brain capillaries by the rosettes of sequestered

parasitized RBCs leading to vascular

occlusion and cerebral anoxia.

 Cerebral malaria manifests as diffuse symmetric encephalopathy characterized by

generalized convulsion

in 10% of adults and up to 50% of children.

 Other defects are retinal hemorrhages, neurologic sequelae, repeated seizures,

and rarely deep coma.

 High mortality rate 20% among adults. and more than 15% among children.
 Soon after invasion of the RBC, the trophozoite produce protein that is deposited

in the erythrocyte surface membrane to form knob-like deformities, This knob

produces specific adhesive proteins [Plasmodium falciparum erythrocyte

membrane protein-I (PfEMP-1)]. which promote aggregation of infected RBCs to

other noninfected RBCs and to capillary endothelial cells.

 These sequestrated RBCs cause capillary plugging of cerebral microvasculature,

which results in anoxia, ischemia and hemorrhage in brain.

2. Black-water fever (malarial hemoglobinuria) :

 this syndrome is sometimes seen in falciparum malaria, particularly in patients, who

have experienced repeated past infections and inadequate treatment with quinine.

 Clinical manifestations include: fever, hemoglobinuria (black colored urine),

bilious vomiting and prostration.

 The pathogenesis is believed to be massive

intravascular hemolysis caused by anti-

erythrocyte antibodies, leading to massive

absorption of hemoglobin by the renal

tubules. It may leads to renal failure and

collapse.

3. Algid malaria:

This syndrome is characterized by peripheral circulatory failure, rapid thready pulse with

low blood pressure and cold clammy skin.

Parasitology

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4. Septicemic malaria:

It is characterized by high continuous fever with dissemination of the parasite to various

organs, leading to multiorgan failure. Death occurs in 80% of the cases.

Chronic Complications of Malaria:

Tropical Splenomegaly Syndrome (hyper-reactive malarial splenomegaly):

condition seen in people of malaria in endemic areas, it happens from abnormal

immunological response to

repeated malaria infection.

Tropical splenomegaly syndrome is characterized by high level of immunoglobulin M

(IgM), decreased C3 and massive splenomegaly.

Quartan malarial nephropathy

It is a chronic complication seen with P. malariae (and possibly with other malarial

species). It occurs due to injury to the renal glomeruli by the immune complexes, resulting

in nephrotic syndrome.

Merozoite-induced Malaria

Natural malaria is sporozoite-induced, the infection being transmitted by sporozoites

introduced through the bite of vector mosquitoes. Injection of merozoites can lead to direct

infection of red cells and erythrocytic schizogony with clinical illness. Such merozoite-

induced malaria may occur in the following situations:

A. Transfusion malaria: Blood transfusion can accidentally transmit malaria; if the

donor is infected with malaria. The parasites may remain viable in blood bank for

1-2 weeks. Pre-erythrocytic schizogony and hypnozoites are absent. Relapse

does not occur and incubation period is short.

B. Congenital malaria: where the parasite is transmitted transplacentally from mother

to fetus.

C. Renal transplantation may lead to malaria if the donor had parasitemia.

D. Shared syringes among drug addicts may be responsible.

Mixed Infections Pathogenesis

In endemic areas it is not uncommon to find mixed infections with two or more species

of malaria parasites in the same individual. Mixed infection with P. vivax and P.

falciparum is the most common combination with a tendency for one or the other to

predominate. The clinical picture may be atypical with bouts of fever occurring daily.

Parasitology

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Laboratory Diagnosis

1. Microscopic examination

Peripheral Blood Smear: the simple and gold standard confirmatory test for the

detection of malarial parasites.

Thin smears:

The amount of blood in thin smear is about 1-

1.5 μL and spread over the

slide by a second slide held at an angle of 45° such that a tail is formed. Thins smears

are stained by Leishman, Giemsa, or Field’s stain. They are used for determining the

species of plasmodium.

Thick smears:

In a thick film, usually three drops of blood are spread over a small area.

The amount of blood in a thick smear is 3-

4 μL. Thick film is more suitable for rapid

detection of malarial parasite, particularly when they are few. thick film is more sensitive

than thin film because it concentrates 20- 30 layers of blood cells in a small area.

• Thin film is examined first at the tail end and if parasites are found, there is no need

for examining thick film.

• It is recommended that 200 oil immersion fields should be examined before the smears

are considered as negative.

2. Quantitative Buffy Coat, and immuno-Fluorescence microscope:

The nucleus of the parasite is detected by acridin-orange stains and appears as

fluorescing greenish-yellow against red back ground.

 The advantage of this test is that it is faster. The disadvantage is that it is less

sensitive than thick film and is expensive.

Parasitology

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3. Serodiagnosis

it is not helpful in clinical diagnosis because it will not differentiate between an active and

past infection. The tests used are indirect hemagglutination (IHA), indirect fluorescent

antibody (IFA) test and enzyme-linked immunosorbent assay (ELISA).

4. Rapid antigen detection tests (RDTS) :

Rapid diagnostic test are based on the detection of antigens using

immunochromatographic methods.

5. Parasite-F test:

This test is based on detection of histidine rich protein-2 (HRP-2) antigen produced by the

asexual stages of P. falciparum expressed on the surface of red cells.

6. Culture of malaria parasite:

RPMl1640 Culture of plasmodia provides a source of the parasites for study of their

antigenic structure, in seroepidemiologic surveys, drug sensitivity tests .

7. Molecular Diagnosis:

nucleic acid probe and PCR.

Summary

 Benign Malaria characterized by a triad of febrile paroxysm, anemia and

splenomegaly.

 Cerebral malaria and Black-water fever are complication of P. falciparum malaria.
 Thin and thick blood smears are the simplest and gold slandered methods for the

diagnosis of malaria.