Malaria

By:
Natnael
Rabia
Obsine
Nardos

Outlines
Introduction
Discovery

Parasite
Taxonomy
Vector

Epidemiology
Life cycle
Pathogenesis
Clinical Manifestation
Complication
Diagnosis
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Discovery
???

~ 6000 yrs.
before

2000y
rs
before

1880 G.C

Dr. Charles
Laveran
I am better than
all because I know
the cause
A Handbook of Prescriptions for
Emergenciesby Ge Hong (284346 CE).

1898 G.C

Carols Finlay
&
Sir Ronald
Ross
But knowing
the cause isn't
everything

Taxonomy
The malaria
parasites belong to
Phylum Protozoa.
Class - Sporozoa
OrderHalmosporidia
Genus
Plasmodium

Parasite
Plasmodium falciparum
(70% in Ethiopia, #1 in
Africa)
P. vivax (most widely
distributed)
P. ovale (limited to Africa)
P. malariae and
P. knowlesi (newly
recognized)

Vector/Definitive
host
An. arabiensis (family of An.
gambiae comlex) = primary
vector
An. funestus
An. phareonsis
An. nili

Transmission
By female anopheles
mosquitoes
Blood transfusion
Contaminated needles
Transplacental

Epidemiology
Prevalence

Global distribution
At risk 40% of the world
population
Prevalence 300-500
million/yr (7 %)
Death 1.5-2.7 million
death/yr
Primarily in Young African
Children (Eth.96/1000 IMR,
140/1000 U5M)

Epidemiology

Epidemiology
75% of Ethiopia is malarious (<2000m)
68% of the population (50 million) at risk
600,000 confirmed and >9 million clinical cases each year
70,000 deaths each year

Health and health related indicator (2005/06) of the

FMOH:
18% of OPD cases (1st)
14% of admission (2nd)
9% of hospital deaths (#1)

Malaria in Ethiopia is
Seasonal

Trend of an epidemic malaria in Adami Tulu District.

Microscopically confirmed malaria cases at Zeway MCL,
1999-2004.

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PATHOGENESIS OF
MALARIA

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Pathogenesis

The cytokines of the proinflammatory cascade like

TNF, ILs, INF-, and NO act as double-edged
swords in the pathogenesis of malaria.
Outcome of malaria infection is determined by
the balance between the pro- and antiinflammatory cytokines.
Excessive levels of cytokines can lead to:=decreased mitochondrial oxygen use and
enhanced
lactate production
= increased cytoadherence
= disturbed auto-regulation of local blood flow
leading to poor circulation and tissue hypoxia
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=dyserythropoiesis
=increased temprature
=reduced gluconeogenesis and hypoglycemia
=myocardial depression and cardiac insufficiency
=loss of endothelial integrity and vascular damage
= selective upregulation of vascular and
intercellular adhesion molecules (ICAMs)
=activation of leukocytes and platelets, promoting
procoagulant activity.

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decreased mitochondrial oxygen use and enhanced lactate

production
Increased RBC loss => decreased oxygen in the circulation
Decreased oxygen in the circulation => cells use other
mechanisms to form ATP

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dyserythropoiesis
Suppression of erythropoeisis by cytokines
Hemozoin-induced apoptosis in developing erythroid
cells

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reduced gluconeogenesis and hypoglycemia

The active moiety released during schizont rupture is

glycophosphatidyl inositol (GPI) moiety that anchors many

membrane proteins .
The purified GPI moieties have strong insulin-mimetic effects that
may be mediated through interference with normal host cell
signaling pathways

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fever
TNF induce production of IL-1
IL-1 is an endogenous pyrogen from macrophages and
fibroblasts.

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Fever cont.

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P falciparuminduced changes to the RBCs

The major parasite adhesin in P. falciparum is P
falciparum Erythrocyte Membrane Protein 1 (PfEMP1)
It results in cytoadherence, rosetting and sequestration.

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 Cytoadherence is believed to have been evolved by

the parasite for avoiding the circulation of trophozoites
and schizonts through the reticular cell filtration beds of
the spleen, where they can be trapped and destroyed
by the combined action of T cell derived cytokines and
phagocytic cells.

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 Cytoadherence leads to sequestration of the parasites

in various organs.
Sequestration of the growing P. falciparum parasites in
these deeper tissues provides them the microaerophilic
venous environment that is better suited for their
maturation and the adhesion to endothelium allows
them to escape clearance by the spleen and to hide
from the immune system.
brain>heart>liver, lungs and kidney>>blood
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 The infected red cells also adhere to the uninfected red

cells, resulting in the formation of red cell rosettes
(rosetting).

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 If the cytoadherence-rosetting-sequestration of infected

and uninfected erythrocytes in the vital organs goes on
uninhibited, it ultimately blocks blood flow, limits the
local oxygen supply, hampers mitochondrial ATP
synthesis, and stimulates cytokine production all these
factors contributing to the development of severe
disease.

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summary

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Clinical manifestations of malaria

Relapse hypnozytes stay in liver as long as 5 yrs *p.vivax & ovale*
Recrudescence short time relapse b/c of partially survival of
erythrocytic stage
* immunity after infection is partial preventing only severe
diseases
Clinical manifestations depend on the parasitic species, the host
*Incubation period of malaria
pa.falciparum 9-14dys
pa.vivax 12-17dys
pa.ovale 16-18dys & pa.malariae 18-40dys

Forms of malaria Infection

asymptomatic infection - subacute or chronic
symptoms
Uncomplicated malaria
Severe malaria-p.falciparum,p.knowleski

Uncomplicated malaria
febrile paroxysms :
fever- high-grade&periodic
sweats, chills,headaches,drowsiness
Anorexia
vomiting, diarrhea
back pain
signs
pallor
hepatosplenomegaly

Severe Malaria: WHO Criteria One or more of the

following plus parasitemia
Unarousable coma or Impaired consciousness
Hypoglycemia (blood glucose < 2.2 mmol/l or < 40 mg/dl)
Severe normocytic anaemia (Hb < 5 g/dl, packed cell volume
< 15%)
Seizures >2/24hrs
Failure to feed
Circulatory collapse
Clinical jaundice plus evidence of other vital organ dysfunction
Gross hemoglobinuria
Abnormal spontaneous bleeding

 Hyperparasitaemia (> 2%/100 000/l in low intensity

transmission areas or > 5% or 250 000/l in areas of
high stable malaria transmission intensity)
Hyperlactatemia (lactate > 5 mmol/l)
Renal impairment (UO<12ml/kg or serum creatinine >
3mg/dl)
Respiratory distress

Congenital Malaria
perinatal or Prenatal transmission
- causes abortions, stillbirths, premature births,
intrauterine growth retardation & neonatal deaths
- symptoms usually appear b/n 10-30 dys

COMPLICATIONS

complications
P. Falciparum
Cerebral coma
Anemia
Pulmonary edema
Shock
Lactic acidosis
Hypoglycemia
Tropical splenomegaly
Pregnancy
nephro
Maternal Death
Stillbirth
Low birth weight
Anemia

P. vivax(P. ovale)
Splenic rupture
anemia(mild)
debilitating fevers

P.malariae
glomerulonephritis leading to
tic syndome

Cerebral malaria/unarousable
coma
definition: unarousable coma with P. falciparum infection
and other causes excluded

confirmed

fatality rate of 2040%

The most serious complication
More likely in patients with parasitemia greater than 5%
Decreased level of consciousness and range in severity
from drowsiness and severe headache to confusion,
delirium, hallucinations, or deep coma

CONTD

sequestration theory
- vascular obstruction by parasitised erythrocytes
The infected red cells stick to endothelium
Infected red cells are more rigid than normal cells
High parasitemia (P. flaciparum infect red cells of all age)

8/13/16

Rosetting

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TK

CONTD
Complete recovery occurs in 50% cases, partial
recovery occurs in 25%, and no recovery in 25%.
Hemiplegia, cerebral palsy, cortical blindness/deafness,
Impaired cognition and learning

Severe anemia
Commonest complication of malaria in children
Peak incident is from 6mo to 2 years
Depend on the severity and duration of parasitemia.
Destruction of both infected and uninfected RBC.
Bone marrow suppression

Hypoglycemia
Occurs in 30% of children
morality rate as high as 40%.
Due to
Diminished hepatic gluconeogenesis
Increase in the consumption of glucose

CONTD
Renal failure
Sequestration in glomerular capillaries
immunoglobulin deposits may be seen
Algid(cold) malaria
overwhelming infection
hypothermia
hypotension

Tropical Splenomegaly Syndrome

Progressive, massive, splenic enlargement
Abdominal distention
vulnerable to trauma
pancytopenia and increased susceptibility to infection

DIAGNOSIS

Clinical Diagnosis
Most prominent is fever, accompanied by chills,
perspiration, anorexia, headaches, vomiting and
malaise
Has traveled or had residence in a malaria-endemic
area within the previous year

Differential diagnosis
Meningitis
Appendicitis
Gastro enteritis
Hepatitis
septicemia

Investigations
Microscopy
Rapid diagnostic test
Serologic tests
- Hb, Hct count
-CBC
Random blood sugar level

Microscopy
Giemsa stain is used
Gold standard
Thick film

Thin film

To detect parasites

Species identification

To measure parasite
density

Quantification e.g.
Percentage of infected
red cell

To monitor response to
treatment

Characteristics of thick and thin

blood films
Thick blood film

Thin blood film

Lysed RBCs

Fixed RBCs

Many layers

Single layer

Large volume

Smaller volume

Good screening test

Good species differentiation

Low density infection can be

detected
More difficult to diagnose species

Low density infection can be missed

Requires more time to read
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Species differentiation on thin films

Feature

P. falciparum

Enlarged infected RBC

Infected RBC shape

Stippling infected RBC

Trophozoite shape
Chromatin dot
Mature schizont
Gametocyte

P. vivax
+

P. ovale

P. malariae

Round

Round, distorted

Oval, fimbriated

Round

Mauer clefts

Schuffner spots

Schuffner spots

none

Large ring, compact

Small ring,
compact

Small ring, appliqu Large ring, amoeboid

Often double

Single

Single

Single

Rare, 12-30
merozoites

12-24 merozoites

4-12 merozoites

6-12 merzoites

Crescent shape

large, round

large, round

compact, round
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8/13/16

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8/13/16

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Rapid diagnostic tests

Detection of antigens derived from malaria
parasites in lysed blood
Antibodies directed against the target
parasite antigens
Performed in about 15 mins

reference
Nelson_Textbook_of_Pediatrics_19th_Ed_2011
Molecular basis for evasion of host immunity and
pathogenesis in malaria
Pathogenesis of Malaria in Tissues and Blood (Beatric
Autino,Yolanda Corbett, Francesco Castelli and
Donatella Taramelli)

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