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Learning objectives
•Define malaria and identify how important the disease is worldwide.

•Understand life cycle of malaria

•Describe its pathogenesis.

•Differentiate its types on the basis of clinical distinction

•Discuss and interpret investigations used in the diagnosis of malaria.

By •Describe preventive and prophylactic measures when going to endemic

areas.
Dr. Nihal Hanafy

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What is Malaria ? Plasmodium species which

infect humans
❑Malaria is a life-threatening mosquito-borne blood Plasmodium vivax
disease caused by a Plasmodium parasite which is
transmitted to humans through the bite of Plasmodium ovale
the female Anopheles mosquito. Plasmodium malariae

❑In Italian: mala aria — “ bad air“ Plasmodium falciparum

Plasmodium Knowlesi

❑The disease causes about 400–900 million cases

of fever and approximately one to three million ❖N.B: It has been found recently that P.knowlesi which
deaths annually. infects monkeys and apes can also infect man.

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▪ The presence of mosquito According to WHO Fact sheet Updated November 2017
vector controls the
presence of the parasite. ❑In 2016, there were an estimated 216 million cases of malaria in 91
countries, an increase of 5 million cases over 2015.
▪ P.Vivax is the predominate
in most of the world. ❑Malaria deaths reached 445 000 in 2016, a similar number (446 000)
to 2015.
▪ P.Falciparum and ovale
present in the tropical ❑The WHO African Region carries a disproportionately high share of
areas. the global malaria burden. In 2016, the region was home to 90% of
malaria cases and 91% of malaria deaths.
▪ Malariae present in mostly
in subtropics and ❑Total funding for malaria control and elimination reached an
temperate zones. estimated US$ 2.7 billion in 2016.

Source: WHO, 2003

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ACCORDING TO WHO UPDATES ON 2021
❑ In 2021, nearly half of the world's population was at risk of
malaria.
❑ That year, there were an estimated 247 million cases of malaria
worldwide.
❑ The estimated number of malaria deaths stood at 619 000 in
2021.
❑ The WHO African Region carries a disproportionately high share
of the global malaria burden. In 2021, the Region was home to
95% of malaria cases and 96% of malaria deaths. Children under
5 accounted for about 80% of all malaria deaths in the Region.
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❑As Malaysia accelerates efforts to eliminate malaria by
2020, zoonotic malaria caused by P. knowlesi has emerged
as a major public health challenge.
❑Starting 2008, the proportion and number of P. knowlesi
cases increased as malaria laboratories established PCR
facilities and P. knowlesi was made notifiable.
❑Reported P. knowlesi cases in Malaysia increased from
376 cases in 2008 to 1604 cases in 2016.
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Plasmodium knowlesi
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Malaria In Malaysia
❑Malaria was a major public health problem in
Malaysia, particularly in peninsular Malaysia and the
state of Sabah and Sarawak
❑However ,Year 2000 to 2015, there was a reduction
of 95% in Malaria cases.
❑ Malaysia was in the pre-elimination phase and the
number of indigenous cases has been steadily
decreasing from 3,147 in 2014 to 1,858 in 2016.
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Plasmodium knowlesi
❑P. knowlesi was first described by Robert Knowles In1931
❑Plasmodium knowlesi, a malaria parasite of long tailed macaque
monkeys, human transmission reported on 2004 in Sarawak and
Borneo. It was then confirmed also in Thailand, Myanmar,
and Philippines.
❑It is the leading cause of malaria in Malaysia, particularly in Sarawak
and Sabah and now well established as an important zoonotic human
pathogen.
❑70% of the malaria cases reported 2016 are attributed to this zoonotic
species.
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❑Populations that are particularly at risk are people who live in or travel
to forests where macaques and vectors are commonly
found.

❑In the early stages it resemble P. falciparum while in the mature blood
stages and gametocytes resemble those of P. malariae .

❑ Misdiagnosed as the relatively benign P. malariae; however,

infections with P knowlesi can be fatal.

❑It should be considered in patients with travel history to forested

areas of Southeast Asia, especially if P. malariae is diagnosed.

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How can we acquire Malaria ?

How does Plasmodium parasite develop in the
body of the patient?
• Only female Anopheles
mosquito feed on blood.

• The female Anopheles

mosquito prefer to feed at How does Plasmodium parasite develop in the
night. body of female Anopheles mosquito?

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Malaria Life Sporogony Pathogenesis of malaria

Cycle Oocyst
Sporozoites

Mosquito Salivary
❑Decrease fragility of RBCs leading to hemolysis.
Zygote Gland

❑Haemolysis of infected and non infected RBCs .

Hypnozoites
Exo- (for P. vivax

Gametogony erythrocytic
(hepatic) cycle
and P. ovale)
❑Liberation of toxic metabolites of the parasite
Gametocytes
leading to toxicity and pyrogen-induced fever .

Merozoites
Schizont
pre- ❑Immunologic response of the host to antigenic
erythrocytic
Erythrocytic
Cycle schizogony material.
Schizont
Merozoites Schizogony
Trophozoites

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What are the patient’s symptoms?

- Infection incubation period

- Prodromal Symptoms : flu-like illness with fever, chills,

- muscle aches, joint pain, vomiting, anemia, and
headache.

- Malaria paroxysm (clinical attack)

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Malaria paroxysm: 3 consecutive stages:

1- Cold stage (15 min):

Chills, cold.

2- Hot stage (2-6 hours) What is the cause of the patient’s symptoms?

Headache, high fever & hot flushed dry skin

3- Sweating stage (hours)

Profuse sweating, temperature falls & feels
weak & exhausted

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Symptoms coincide with: Malaria paroxysms

Repeated as follows:
- Rupture of infected RBC’s. – Every 48 hours in P.v. and P.o. (tertian)
– Every 72 hours in P.m. (quartan)
- Release of parasite metabolites. – Every 36-48 hours in P.f.(sub tertian or irregular )
– Every 24 hours in P.knowelsi
Haemozoin • Paroxysms repeated over a period of
- Host immunologic response. 2 weeks or more with decreasing
Metabolites
intensity then stops.
• Termination of paroxysms indicate elimination of
This is the Pathogenesis of clinical attack infection.

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Anaemia occurring in Plasmodium infected human

If the clinical presentation is repeated after a period
▪ Type of Anaemia: Haemolytic anaemia of clinical cure, How can we verify the recurrence of
clinical presentation in this case?
Plasmodium parasite invades:

- Reticulocytes only (in P.vivax and P.ovale). Restricted

anaemia Relapse
- Old RBCs only (in P.malariae).

- RBCs of any age (in P.falciparum). Severe

anaemia Recrudescence
-Hepatosplenomegaly as a result of enhanced phagocytosis
of RBC’s remnants and other debris produced by schizogony

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Life cycle of P.vivax & P.ovale

Invades Plasmodium sporozoite
patient’s
liver cell Relapse means
recurrence of clinical attack
due to reactivation of
hypnozoites in patient’s liver
parynchymal cell
Continue development

Relapse
Occurs in P.vivax & P.ovale infection

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Recrudescence means Complications:

Recurrence of clinical attack due to
presence of low-grade parasitaemia
when the patient is debilitated
- P.vivax, P.ovale and P.malariae are relatively benign.
-Chronic P.malariae infection immune- complex deposition
on the glomerular walls leading to nephrotic syndrome.

Recrudescence

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P.falciparum
parasite antigens are expressed on the surface of
infected red cells containing trophozoites
and schizont stages and is called knobs
-P.falciparum infection is usually severe and fatal due
to Partial occlusion of Capillaries .
Knobs
Parasitized RBC’s develop knobs on their surface
Knobs adhere to receptors found on endothelium of adhere to each other and to specific receptors on the
blood capillaries blood supply epithelial cells of blood capillaries of internal organs
anoxia and necrosis of tissue occlusion leading to blockage of blood supply and
therefore anoxia and necrosis of tissue.
Partial occlusion of
Normal RBC blood capillary

Infected RBC Blood capillary

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Example: - Dysenteric Malaria

- Cerebral malaria
▪ This is the most serious complication leading to death
▪ It is due to brain hypoxia resulting from local capillary
obstruction leading to poor blood flow.
• Not common but extremely serious.
• Due to focal ischemic changes in the intestinal wall capillary
bed.
• The condition is referred to as choleraic malaria.
- Algid Malaria

▪ Patients present with severe headache, drowsiness, Involving the adrenal glands include circulatory collapse
confusion and coma. Rapid development of hypotension

▪ Might be the first sign of infection impaired vascular perfusion.

Temperature drops suddenly and patient become Shocked.

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Black Water Fever

Are certain humans naturally resistant to
▪ High rate of parasitemia in P.falciparum infection Malaria infection?

▪ Massive intravascular hemolysis due to autoantibodies

(both parasitized and non parasitized) with consequent
hemoglobinuria (Black Urine), intense jaundice and
anuria (passing less than 50 milliliters of urine in a
day) X NO

▪ Quinine drug was once thought to be the cause. YES

The most probable explanation for blackwater fever is
an autoimmune reaction apparently caused by the interaction
of the malaria parasite and the use of quinine.

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Several host factors determine the outcome of

exposure to malaria:
- Absence of Duffy antigen. Absent Duffy Duffy Ag helps
Duffy antigen X
•Naturally-acquired immunity. People in endemic areas. Resistant to P.vivax infection. antigen P. vivax
merozoite to
Antibodies block merozoites resulting in low level of enter patient’s
Parasitemia and low grade symptoms – (Concomitant red blood cell
immunity). - Haemoglobin S (in sickle-cell disease)
Shape of RBC and type of Hb are not
•Infants are also relatively immune to malarial infections suitable for P.falciparum parasite growth.
during the first months of life due to % HbF & passive
immunity from maternal antibodies.
- Deficiency of G6PD enzyme.
P.falciparum parasite needs this enzyme for its growth.

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Malaria Lab Diagnosis

Blood smears

• Thin and thick stained blood films

How can we diagnose Malaria?
• Remains the GOLD STANDARD for
diagnosis
• Thin blood film can distinguishes between
species.

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What can the lab doctor see by microscopic examination

of these Giemsa stained blood films? Ring form

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P.vivax
Trophozoite

Can Plasmodium infection be diagnosed by

laboratory methods other than blood film
examination?
Ring form Trophozoite

P.Malariae trophozoite
Gametocyte

ring X NO
Schizont Gametocytes
YES

P.ovale
trophozoite P. falciparum ring & gametocyte

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Buffy Coat Method

A technique used for collection of parasite from blood sample Malaria Diagnosis
• Clinical Diagnosis
Plasma
• Antigen Detection by Rapid diagnostic test
WBCs, platelets, parasite
(RDT detects LDH/HRPS2)
Buffy coat

RBCs • Serology IF & ELISA (Serology does not

detect current infection but rather
measures past exposure.
Centrifugation of • Polymerase Chain Reaction(18S rDNA)
blood sample
Patient’s
blood

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Malaria Antigen Detection TREATMENT

• Treatment should be as soon as possible.

• The WHO recommends that those in endemic areas,

• Immunologic assays to detect
treatment should be started within 24 hours after the
specific antigens
first symptoms appear.
• Commercial kits now available
as immunochromatographic
rapid diagnostic tests (RDTs), • Patients with severe malaria should be hospitalized if
used with blood possible.

• In areas where malaria is not endemic, all patients with

• Cannot detect mixed infections malaria (uncomplicated or severe) should be kept under
• Cross reactivity with rheumatoid factor clinical observation.
reportedly corrected

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There are three main factors in determining treatment

1. - The infecting species of Plasmodium parasites. Available drugs are classified into:

2. - The clinical situation of the patient.

• Mild malaria oral medication. 1. Tissue schizonticides i.e.Drugs that destroy parasite
• Severe malaria. (IV) treatment and fluids. stages in the liver
• Malaria a serious threat to pregnant women and her pregnancy.

2. Blood schizonticides i.e.Drugs that destroy parasite

3. - The drug susceptibility of the infecting parasites. stages in the blood
• Different areas have malaria types that are resistant
to certain medications.

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MALARIA PREVENTION &CONTROL

Treatment of severe Malaria (WHO) states the so-called

‘‘ABCDE of malaria’’ as a basis for protection:
Antimalarial drugs, Consider ICU referral, IV fluids,
O2 A = awareness
Blood transfusion, Dialysis, Vital signs monitoring B = bite prevention
C = chemoprophylaxis
D = diagnosis.
E = emergency stand-by treatment.

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