Malarial Pathogenesis

By: Kareem Waleed Hamimy

6th Year Medical Student
Kasr Al Ainy - Cairo University
A short introduction
 Malaria
Why?
What?
How?
Who?
Where?
 Pathogenesis
 Clinical picture
Why Malaria ?
 One of the most common infectious
diseases & an enormous public-health
problem.
 Each year, it causes disease in
approximately 650 million people & kills
1-3 million, most of them young children
in Africa.
 At least one death every 30 seconds.
What is Malaria ?
 Malaria is a vector-borne infectious
disease caused by protozoan parasites
of the genus plasmodium.
 The most serious forms of the disease
are caused by Plasmodium falciparum
and Plasmodium vivax.
How?
Who?
 Malaria is a disease which
can be transmitted to
people of all ages, bitten
by a vector
 Young children and
pregnant women in high
transmission areas are at
a large risk.
Where?
Malarial Pathogenesis
 Hepatic phase
Sporozoites infect hepatocytes, multiplying
asexually & asymptomatically for a period of
6–15 days.
Then they differentiate into merozoites 
rupture the hepatocytes  escape to blood
stream undetected (wrapping itself in the cell
membrane of the infected host liver cell).
Malarial Pathogenesis
 Erythrocytic phase
Within the red blood cells the parasites
multiply further, again asexually, periodically
breaking out of their hosts to invade fresh
red blood cells.
 p.vivax and p.ovale
 do not immediately develop into merozoites
They develop first to Hypnozoites (dormant
form) for 6-12 month leading to long
incubation and late relapses
Malarial Pathogenesis
 PfEMP1
Plasmodium falciparum erythrocyte membrane
protein 1
Adhesion (protective) protein produced by
p.falciparum expressed on surface of RBCs
causing it to stick to the walls slowing its lysis in
spleen.
Block endothelial venules cerebral &
placental malaria.
Extreme diversity  not a good immune
targets.
Pathogenesis of clinical picture
 Prodromal symptoms (influenza like)
Hepatic phase where the parasite asexually
and asymtomatically multiply.
 Malarial paroxysms
Decreased osmotic fragility  rupture of
RBCs
Release of metabolites & toxins
Release of cytokines such as TNF and
interleukin-1 from macrophages, resulting in
chills and high grade fever.
Pathogenesis of clinical picture
 Anemia
Febrile paroxysmal hemolysis
Immune & Non Immune hemolysis
Increased splenic clearance
Dyserythropoeisis in BM
Drug induced hemolysis
 Bone marrow
Iron sequestration  Dyserythropoeisis
Dysthrombopoeisis
Pathogenesis of clinical picture
 Spleen
Splenomegaly
○ Edema of the pulp
○ RES hyperplasia
○ Increased phagocytic function
○ New guinea “Tropical splenomegaly syndrome”
 Liver
Hepatomegaly (hepatic phase)
Malarial pigments  greyish black
Falciparum  malarial hepatitis
Pathogenesis of clinical picture
 Due to adherence factor of falciparum
 blocking of venules of organs lead to
a lot of manifestations as
Cerebral malaria (severe headache,
drowsiness, confusion, coma)
 Placental malaria (premature delivery,
intrauterine growth retardation iURD)
Dysenteric malaria (abdominal pain,
vomiting, GIT bleeding )
Pathogenesis of clinical picture
 CVS
Anemia leads to
○ Hypotension
○ Tachycardia
○ Muffled heart sounds
 Kidney
Immune complexes  Nephrotic syndrome
○ Albuminuria
○ Edema
○ hypertension
 Malarial
Infections

High
Secondary Clinical Grade
Infection
Picture Fever

Anti
Malarial
Drugs
Any Questions ?
THANK YOU