3. INTRODUCTION
•Malaria is an acute and chronic disease caused
by obligate intracellular protozoa of the genus
Plasmodium.
•Malaria parasite belongs to Phylum:
Apicomplexa, Class: Haematozoea, Order:
Haemosporida, Genus: Plasmodium
4. AETIOLOGY
•Malaria`s causative factor is acquired but genetic
polymorphism/alterations can confer immunity or
succeptibility. This will be discussed later.
•Malaria is a protozoal disease caused by any one or
combination of five species of plasmodia:
Plasmodium vivax, Plasmodium falciparum,
Plasmodium ovale, Plasmodium malariae and
Plasmodium knowlesi.
6. •The most important of these is P. falciparum
because it can be rapidly fatal and is
responsible for the majority of malaria related
deaths
7. MODE OF TRANSMISSION
•There are 3 major means of malaria
transmission:
1. Primarily by Bite from female anopheles
mosquito.
2. Vertical transmission/Congenital.
3. Transfusion malaria/organ transplant.
8. EPIDEMIOLOGY
•The disease is endemic in several parts of the world,
especially in tropical Africa, parts of South and Central
America, India and South-East Asia.
•The highest transmission rates are found in countries
in subSaharan Africa
•It is a leading cause of disease and death among
children under five years, pregnant women and non-
immune travellers/immigrants.
9. •P falciparum is found in tropical regions and
causes the most severe and fatal disease.
• P ovale is the least common malarial species
and is endemic in Africa.
10. LIFE CYCLE/PATHOGENESIS
•The life cycles of the Plasmodium species are
similar, although P. falciparum differs in ways
that contribute to its greater virulence.
•The life cycle of Plasmodium species is simple,
as it involves only humans and mosquitoes, but
the development of the parasite is complex, as it
passes through several morphologically distinct
forms
11. •The life cycle can be divided into two phases:
1.Asexual phase in the intermediate
host(SCHIZOGONY): Human
a. Exoerythrocyctic phase
b.Erythrocytic phase
2. Sexual phase in the definitive host(SPOROGONY):
Anopheles mosquito
c. Gametocytic phase
12. HUMAN
•The infectious stage of Plasmodium, the
sporozoite, is found in the salivary glands of
female mosquitoes.
•During a blood meal, a malaria-infected female
Anopheles mosquito inoculates sporozoites
into the human host.
13. •These sporozoites disappears into the
hepatocytes within 30-60 minutes
•They attach to and invade liver cells by binding
to the hepatocyte receptor for the serum
protein thrombospondin and properdin.
•Important proteins on plasmodium are
CS(circumsporozoite protein) and TRAP
(Thrombospondin related anonymous protein
14. •Within liver cells, malaria parasites multiply,
forming mature schizonts which ruptures
releasing as many as 30,000 merozoites
(asexual, haploid forms).
•P. vivax and P. ovale form latent hypnozoites in
hepatocytes, which cause relapses of malaria
weeks to months after initial infection.
15. •The infection of the liver and development of
merozoites is the exoerythrocytic phase.
•NB: This stage is asymptomatic.
16. •Once released from the liver, Plasmodium
merozoites use a lectin-like molecule to bind to
sialic acid residues on glycophorin molecules on
the surface of red cells and invade by active
membrane penetration.
•Within the red cells the parasites grow in a
membrane-bound digestive vacuole, hydrolyzing
hemoglobin through secreted enzymes.
17. •The trophozoite is the frst stage of the parasite
in the red cell and is defned by the presence of
a single chromatin mass. The next stage, the
schizont, has multiple chromatin masses, each
of which develops into a merozoite.
•The ring-cell stage occurs when trophozoites
mature into schizonts in the red blood cells,
which rupture and release merozoites
20. •Upon lysis of the red cell, the new merozoites
infect additional red cells.
•Paroxysmal fever, chills, and rigors
characteristic of malaria occur when the
merozoites are released into the blood.
•This is the erythrocytic stage
21. •Some parasites differentiate into sexual
erythrocytic
stages (gametocytes).
• The gametocytes, male (microgametocytes)
and female (macrogametocytes), are ingested
by an Anopheles mosquito during a blood meal
22. RECRUDESCENCE
•This simply means relapse/recurrence.
•Recrudescence of malaria can occur via 2
mechanisms:
•1. Sequestration of Schizont in RBC
•2. Formation of hypnozoites in certain
Plasmodium species (P. vivax and P. ovale)
23.
24. MOSQUITO
•While in the mosquito’s stomach, the
microgametes penetrate the macrogametes
generating zygotes.
• The zygotes in turn become motile and
elongated (ookinetes), which invade the midgut
wall of the mosquito where they develop into
oocysts.
25. •The oocysts grow, rupture, and release
sporozoites which make their way to the
mosquito’s salivary glands.
• Inoculation of the sporozoites into a new
human host allows the malaria life cycle to
continue
26.
27.
28.
29. •Plasmodium falciparum causes more severe disease
than the other Plasmodium species do because of the
following features which account for its greater
pathogenicity:
1. P. falciparum is able to infect red blood cells of any
age, whereas other species infect only young red cells
(such as P. vivax and P. ovale) or old red cells (such as
P. malariae) which are a smaller fraction of the red cell
pool.
30. 2. P. falciparum causes infected red cells to
clump together (rosette) and to stick to
endothelial cells lining small blood vessels
(sequestration), causing obstruction of small
blood vessels by thrombi formation.
Several proteins, including P. falciparum
erythrocyte membrane protein 1 (PfEMP1),
associate and form knobs on the surface of red
cells (Fig. 8-46). PfEMP1 binds to ligands on
endothelial cells, including CD36,
31. 3. Red cell sequestration decreases tissue
perfusion and leads to ischemia, which is
responsible for the manifestations of cerebral
malaria, the major cause of death in children
with malaria.
4. It does not have exo-erythrocytic stage.
5. One red cell may contain more than one
parasite.
32. HOST RESISTANCE
•Host resistance to Plasmodium can be intrinsic or
acquired.
•Intrinsic resistance stems from inherited
alterations that reduce the susceptibility of red
cells to productive Plasmodium infections.
•Most of these are caused by mutations which are
deleterious in homozygous form, suggesting that
they are maintained in populations due to a
selective advantage for heterozygous carriers
33. 1. Mutations in globin genes - sickle cell disease
(HbS, HbC disease (hemoglobinopathies))
2. Mutations leading to globin defciencies—α-
andβ-thalassemia.
3. Mutations affecting red cell enzymes—glucose-
6-phosphate dehydrogenase (G6PD) deficiency
34. The mechanisms of the protective effects of the above
three types of mutations are less well understood, but
likely involve a favorable shift in the balance between the
growth of intraerythrocytic parasites and their clearance
by host phagocytes.
4. Mutations causing red cell membrane defects—
absence of DARC (Duffy surface blood group), band 3,
spectrin.
35. •P. vivax enters red cells by binding to the Duffy
blood group antigen, and most of the population
Africa is not susceptible to infection by P. vivax
because. as most Africans are Duffy blood group
negative i.e. they do not have the Duffy antigen
5. Foetal haemoglobin (HbF): High levels of HbF
occur in neonates, and in some people with
inherited haemoglobin variants, protect against
36. • Resistance may also be acquired following repeated or prolonged
exposure to Plasmodium species, which stimulates a partially
protective immune response.
• Individuals living where Plasmodium is endemic often gain partial
immune-mediated resistance to malaria, evidenced by reduced
illness despite infection. Antibodies and T lymphocytes specifc
for Plasmodium reduce disease manifestations, although the
parasite has developed strategies to evade the host immune
response.
• P. falciparum uses antigenic variation to escape from antibody
responses to
PfEMP1. Each haploid P. falciparum genome has about 50 var
38. SPLEEN
•Insertion of parasite proteins into the red cell
membrane leads to recognition by macrophages
particularly in the spleen leading to phagocytosis
and destruction. Macrophages with engulfed
parasitized red cells are also numerous.
•Malarial pigment liberated by destroyed red cells
accumulates in the phagocytic cells of the
reticuloendothelial system resulting in enlargement
39. •Plasmodium falciparum infection also leads to
splenomegaly, due to both congestion and
hyperplasia of the red pulp and the spleen may
eventually exceed 1000 gm in weight.
•Haemorrhages and infarcts may be present
•In chronic infections, the spleen becomes
increasingly fibrotic and brittle, with a thick
capsule and fibrous trabeculae. The parenchyma is
gray or black because the phagocytes contain
granular, brown-black, faintly birefringent
41. LIVER
•Malarial pigment liberated by destroyed red cells
accumulates in the phagocytic cells of the
reticuloendothelial system resulting in enlargement
of and liver. (hepatomegaly)
•With progression of malaria, the liver becomes
enlarged and
pigmented. Kupffer cells are heavily laden with
malarial pigment, parasites, and cellular debris,
44. KIDNEY
•The kidneys are often enlarged and congested with
a dusting of pigment (malaria pigment) in the
glomeruli and haemoglobin casts in the tubules.
•The cortico-medullary capillaries show parasitized
RBCs and haemoglobin in tubules.
•Acute tubular necrosis and Acute renal failure.
•In falciparum malaria, there is massive absorption
of haemoglobin by the renal tubules producing
blackwater fever (haemoglobinuric nephrosis).
45. BRAIN
• In cerebral malaria caused by P. falciparum, brain vessels are
plugged with parasitized red cells. Around the vessels there
are ring hemorrhages that are probably related to local
hypoxia incident to the vascular stasis and small focal
inflammatory reactions (called malarial or Dürck
granulomata).
• Parasitised erythrocytes in falciparum malaria are sticky and
get attached to endothelial cells resulting in obstruction of
capillaries of deep organs such as of the brain leading to
hypoxia and death. If the patient lives, microhaemorrhages
46. •With more severe hypoxia, there is
degeneration of neurons, focal ischemic
softening, and occasionally scant inflamatory
infltrates in the meninges.
•At autopsy, cerebral malaria is characterised by
congestion and petechiae on the white matter.
•Cerebral oedema/congestion with pink
appearance of the brain.
47.
48.
49. HEART
•Nonspecific focal hypoxic lesions in the heart
may be induced by the progressive anemia
and circulatory stasis in chronically infected
people.
• In some, the myocardium shows focal
interstitial infiltrates.
50. CARDIOVASCULAR SYSTEM/BLOOD
• Hemglobinemia
• Parasitemia
• Hyperbilirubinemia
• Thrombi formation/DIC
• RBC Hemolysis leading to low level RBC in blood
• Inflammation in small capillaries
• Ring necrosis
53. •Finally, in the non-immune patient, pulmonary
edema or shock with disseminated
intravascular coagulation may cause death,
sometimes in the absence of other
characteristic lesions.
54. CLINICAL MANIFESTATION
Malaria is a multisystem disease. The main clinical
features of malaria are cyclic peaks of high fever
accompanied by chills, anaemia and splenomegaly.
Common clinical features are:
•Vomiting
•Diarrhoea – more commonly seen in young children
and, when vomiting also occurs, may be misdiagnosed
as viral gastroenteritis.
•Convulsions – commonly seen in young children.
55. •Pallor – resulting mainly from the lysis of red
blood cells. Malaria also reduces the synthesis
of red blood cells in the bone marrow
•Jaundice – mainly due to haemolysis.
•Marked diaphoresis
•Anorexia
•Cough
•Headache
•Malaise
56. DIAGNOSIS
•Gold standard for diagnosis of malaria is blood
film examination both Thick/thin blood film
•Others are
•Antigen detection
•Antibody detection
•FBC
•PCR
57. REFERENCES
•Robbins and Cotran Pathologic Basis of Disease 9e -
Kumar Abbas Aster (Elsevier 2015)
•Harsh Mohan - Textbook of Pathology, 6th Edition
•the big picture MEDICAL MICROBIOLOGY Neal R.
Chamberlain, PhD
•Malaria presentation by Prof A.O. Aboderin
•Protozoal infections presentation by Dr B.O. Olopade
•The free online search engine. Google www.google.com
