Clinical aspect of

Malaria

Pugud Samodro
Bag/SMF Ilmu Penyakit Dalam
FKIK Unsoed/ RSUD Prof Margono Soekarjo
Purwokerto
 What is Malaria?
 Parasitic infection of human red blood cells
 4 species can infect humans
 Plasmodium falciparum
 Plasmodium vivax
 Plasmodium malariae
 Plasmodium ovale

Pictures of P. falciparum
 Etiology
 Causative organism: Plasmodia
 P. Vivax: tertian malaria
 P. Malariae: quartan malaria
 P. Falciparum: malignant malaria
 P. Ovale: tertian malaria

 Pathogenicity: merozoite, malarial pigment &

products of metabolism
 Plasmodium falciparum
 Most dangerous form of malaria
 Risk of cerebral malaria, renal failure, acute respiratory
distress syndrome, severe anemia
 Prompt treatment is essential
 Untreated infection in a non-immune person would
likely be fatal
 Once person is treated and cured, there is no risk of
relapse (but you can get infected again…)
 P. falciparum has no dormant liver stage (hypnozoite)
 P. vivax and P. ovale

 Less likely to be life threatening than P.

falciparum
 Symptoms (especially fever) can still be
dramatic
 Different drugs are used to treat blood and liver
stage parasites
 Etiology
 Two period:
 human - whole asexual reproduction
 mosquito - sexual parasitic stage
 Two host:
 human - intermediate host
 mosquito - final host
 notes:
 clinical symptoms: erythrocytic stage
 relapse: exerythrocytic stage
 infectivity: sporozoite
 Epidemiology
 Source of infection
Patient, parasite carrier
 Route of transmission
 female mosquito biting person
 blood transfusion
 Susceptibility:
 universal susceptibility
 no-cross-immunity
 re-infection
 Epidemic features:
 sporadic or endemic, tropic or subtropic
 What is the Malaria Vector?

 Spread by bite of infected female

Anopheles mosquitoes

 Night-biting mosquitoes

 Indoor-biting mosquitoes
 Pathogenesis
 Mechanism of attack
merozoite
RBC rupture malaria pigment
products of metabolism
blood stream allergy

 P. Falciparum: produce microvascular disease

 magnitude of the parasitemia & age of patient
 no specific Ab or cell -mediated response
Malaria Lifecycle
Human Liver Stages

Mosquito Stages
Exo-erythrocytic
(hepatic) Cycle:

Sporogonous Cycle: Human Blood Stages

P. falciparum

Erythrocytic Cycle:
Gametocytes
P. vivax
P. ovale
P. malariae
 Pathology
 Anemia:
 P. Vivax - retiform RBC
 P. Malariae - mature RBC
 P. Falciparum - every RBC
 Prolifeation of mononuclear phagocyte
 hepatomegaly
 splenomegaly
 Cerebral edema & congestion
Symptoms of Malaria

 Fever is by far the most common symptom, but

is by no means the only one

 Often can have constellation of symptoms

described as “flu-like”

 Other symptoms can include: chills, fatigue,

weakness, headache, nausea, vomiting,
diarrhea, muscle aches, mental status changes
 Clinical manifestation
Incubation period:
quartan malaria: 24-30 day
tertian malaria: 13~15 day
malignant malaria: 7~12 day
 Clinical manifestation
Typical attack
 Chill: abrupt onset, shivering, pale face,cyanosis. Last
10 min or 1~2hr.
 High fever: T rise to 40oC with malaise, myalgia, thirsty.
Last 2~6 Hr.
 Sweating: profuse sweating with restlessness
 regular 48 hr. or 72 hr. Cycle
 Clinical manifestation
Signs
 anemia
 splenomegaly
 hepatomegaly, ALT elevate
 Clinical manifestation
Perniciouse attack: cause by P. Falciparum
 cerebral malaria
high fever, headache, vomiting, convulsion delirum,
respiratory failure
 hyperpyrexia type
T> 420C, convulsion, delirium
 Relapse: early relapse - <3m,
later relapse - >6m
 Clinical manifestation
Malaria caused by transfusion
 incubation period: 7~10 day
 no exerythrogenic phase, no relapse
 Complications
 Black- water- fever:
 cause:1/inadequate G-6-PD
2/The toxin release by malarial parasite
3/Allergic reaction to anti-malarial drugs
 feature:1/chill & fever
2/dark red or black urine
3/severe hemolytic anemia
 Acute glomerulonephritis
 Malaria Mortality
2 main ways it kills:
 Anemia
 Parasites destroy red blood cells
 Associated with increased mortality
 Cerebral malaria
 Damages brain and other vital organs
 Fatality rate of 15% or more
 Laboratory Findings
 Blood picture: decrease in RBC & Hb
 blood film for parasite
 serological examination
 ELISA for P. antigen
 DNA hybridization
 Plasmodium vivax

Ring stage
Trophozoite
Schizont
Gametocyte
 Plasmodium malariae

Ring stage
Trophozoite
Schizont
Gametocyte
 Plasmodium ovale

Ring
Trophozoite
Schizont
Gametocyte
 Diagnosis
Epidemiological data
 endemic zone
 blood transfusion
Clinical manifestation
Laboratory findings
Diagnostic treatment:
 chloroqunine for 3 days
 Differential Diagnosis
Typhoid fever
Septicemia
Leptospirosis
Encephalitis B
 Roll Back Malaria (RBM)
 Founded by:
World Health Organization (WHO),
United Nations Development Program (UNDP),
United Nations Children's Fund (UNICEF)
and World Bank
 Includes national governments, civil society and
non-governmental organizations, etc.
 Provides framework for coordination between
Ministries of Health and various organizations
 Roll Back Malaria (RBM)
 The goal of Roll Back Malaria, established as a
health initiative by WHO and its partners in 1998, is
to halve the world's malaria burden by 2010.
 At the Africa Summit on RBM, April 2000, Heads of
State or senior representatives from 44 malaria-
afflicted countries in Africa agreed to a series of
interim goals to be attained by 2005.
 Global program with clear strategies
 Provides framework for Action
 Touts prevention and treatment
 Roll Back Malaria (RBM)
Goals - At least 60%
 At least 60% of those with malaria should be able to
access and use correct, affordable and appropriate
treatment within 24 hours.
• At least 60% of those at risk of malaria, particularly
children under five years of age and pregnant women
should use insecticide treated mosquito nets.
 At least 60% of pregnant women at risk of malaria
should have access to chemoprophylaxis or intermittent
presumptive treatment.
 Treatment
Anti-malarial drugs
Chloroquine-susceptable infection
 chloroquine : 1g /d, for 3 day, p.o.
 primaquine: for 8day, p.o.
Chloroquine-resistant infection
 mefloguine:
 artemisinine
 Treatment
 Pernicious attack
 Chloroquine: 10mg/kg iv drop in 4 hr. Then
5mg/kg, iv drop in 2 hr.
 Quinine: 500mg iv drop in 4 hr.
 Radical therapy
Chloroquine (3 day) + primaquine ( 8 day )
P- falciparum resistance to chloroquine
Source: WHO global database on drug resistance 1996-2004

Countries with at least one study indicating chloroquine total failure rate > 10%
Chloroquine total failure rate < 10%
No failure reported
No recent data available
P. falciparum resistance to sulfadoxine/pyrimethamine
Source: WHO global database on drug resistance 1996-2004

Countries with at least one study indicating pyrimethamine-sulfadoxine total failure rate > 10%
P yrimethamine-sulfadoxine total failure rate < 10%
No failure reported
No recent data available
 P. falciparum resistance to mefloquine
Source: WHO global database on drug resistance 1996-2004

Countries with at least one study indicating mefloquine total failure rate > 20%
Countries with at least one study indicating mefloquine total failure rate > 10%
Mefloquine total failure rate < 10%
No failure reported
No recent data available
 P.vivax malaria distribution and
Reported Treatment or Prophylaxis Failures or True
Resistance, 2004

Vivax resistance to CQ confirmed in

Guyana, Indonesia and Peru

Source: WHO RBM Department, 2004

 Rationale for
antimalarial combination therapy

 Advantages of combining two or more antimalarial drugs:

 First cure rates are usually increased.
 Second, in the rare event that a mutant parasite which is resistant to
one of the drugs arises de-novo during the course of the infection, it will
be killed by the other drug. This mutual protection prevents the
emergence of resistance.
 Both partner drugs in a combination must be independently effective.
 Risks: Increased costs and increased side effects
 The choice of
artemisinin combination therapy (ACT)

Combinations which have been evaluated:

chloroquine
amodiaquine
mefloquine sulfadoxine-pyrimaethaminine
artemisinin + piperaquine
mefloquine
proguanil-dapsone
mefloquine artesunate + chlorproguanil-dapsone
artemether + lumefantrine
atovaquone-proguanil
clindamycin
mefloquine tetracycline
dihydroartemisinin + piperaquine doxycycline
naphthoquine

There are now more trials involving artemisinin and its derivatives than
other antimalarial drugs, so although there are still gaps in our
knowledge, there is a reasonable evidence base on safety and efficacy
from which to base recommendations.
 Response to increasing resistance
Combination therapies
recommended by WHO
WHO Technical Consultation on
“Antimalarial Combination Therapy” – April 2001

FDC
• Artemether/lumefantrine
• Artesunate + amodiaquine
ACTs
• Artesunate + SP
• Artesunate + mefloquine
 Prevention
 Drug prophylaxis
 chloroquine: 0.3g once a week
 doxycycline
 Kill mosquito
 Vaccination
TOGETHER WE CAN BEAT MALARIA
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