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
RBC rupture
merozoite
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 malariaafflicted 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
artemisinin + piperaquine
mefloquine
artemether + lumefantrine
sulfadoxine-pyrimaethaminine
mefloquine
proguanil-dapsone
artesunate +
mefloquine
dihydroartemisinin + piperaquine
naphthoquine
chlorproguanil-dapsone
atovaquone-proguanil
clindamycin
tetracycline
doxycycline
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
• Artesunate + SP
• Artesunate + mefloquine
ACTs
Prevention
 Drug prophylaxis
 chloroquine: 0.3g once a week
 doxycycline
 Kill mosquito
 Vaccination
TOGETHER WE CAN BEAT MALARIA
THANK YOU FOR LISTENING