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Pugud SamodroBag/SMF Ilmu Penyakit Dalam
FKIK Unsoed/ RSUD Prof Margono SoekarjoPurwokerto
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What is Malaria? Parasitic infection of human red blood
cells 4 species can infect humans
Plasmodium falciparumPlasmodium vivaxPlasmodium malariaePlasmodium ovale
Pictures of P. falciparum
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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
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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)
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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
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EtiologyTwo period:
human - whole asexual reproductionmosquito - sexual parasitic stage
Two host:human - intermediate hostmosquito - final host
notes:clinical symptoms: erythrocytic stagerelapse: exerythrocytic stage infectivity: sporozoite
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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
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What is the Malaria Vector?
Spread by bite of infected female Anopheles mosquitoes
Night-biting mosquitoes
Indoor-biting mosquitoes
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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
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Sporogonous Cycle:
Mosquito Stages
Gametocytes
P. falciparum
P. vivaxP. ovaleP. malariae
Human Liver Stages
Exo-erythrocytic(hepatic) Cycle:
Human Blood Stages
Erythrocytic Cycle:
Malaria Lifecycle
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Pathology
Anemia:P. Vivax - retiform RBCP. Malariae - mature RBCP. Falciparum - every RBC
Prolifeation of mononuclear phagocytehepatomegalysplenomegaly
Cerebral edema & congestion
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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
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Clinical manifestation
Incubation period: quartan malaria: 24-30 day
tertian malaria: 13~15 day
malignant malaria: 7~12 day
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Clinical manifestation
Typical attackChill: 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 restlessnessregular 48 hr. or 72 hr. Cycle
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Clinical manifestation
Signsanemiasplenomegalyhepatomegaly, ALT elevate
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Clinical manifestation
Perniciouse attack: cause by P. Falciparum
cerebral malaria high fever, headache, vomiting, convulsion delirum,
respiratory failure
hyperpyrexia type T> 420C, convulsion, deliriumRelapse: early relapse - <3m, later relapse - >6m
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Clinical manifestation
Malaria caused by transfusion incubation period: 7~10 day no exerythrogenic phase, no relapse
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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
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Malaria Mortality 2 main ways it kills: Anemia
Parasites destroy red blood cellsAssociated with increased mortality
Cerebral malariaDamages brain and other vital organsFatality rate of 15% or more
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Laboratory Findings
Blood picture: decrease in RBC & Hb blood film for parasite serological examination
ELISA for P. antigen DNA hybridization
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Plasmodium vivax
Ring stage
Gametocyte
Trophozoite
Schizont
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Plasmodium malariae
Ring stage
Gametocyte
Trophozoite
Schizont
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Plasmodium ovale
Ring
Trophozoite
Schizont
Gametocyte
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Diagnosis Epidemiological data
endemic zone blood transfusion
Clinical manifestation Laboratory findings Diagnostic treatment:
chloroqunine for 3 days
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Differential Diagnosis Typhoid fever Septicemia Leptospirosis Encephalitis B
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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
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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
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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.
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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
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TreatmentPernicious 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 )
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Countries with at least one study indicating chloroquine total failure rate > 10%
No failure reported
Chloroquine total failure rate < 10%
No recent data available
P- falciparum resistance to chloroquine Source: WHO global database on drug resistance 1996-2004
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Countries with at least one study indicating pyrimethamine-sulfadoxine total failure rate > 10%
No failure reported
P yrimethamine-sulfadoxine total failure rate < 10%
No recent data available
P. falciparum resistance to sulfadoxine/pyrimethamine Source: WHO global database on drug resistance 1996-2004
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Countries with at least one study indicating mefloquine total failure rate > 20%
No failure reported
Mefloquine total failure rate < 10%
No recent data available
Countries with at least one study indicating mefloquine total failure rate > 10%
P. falciparum resistance to mefloquine Source: WHO global database on drug resistance 1996-2004
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P.vivaxP.vivax malaria distribution malaria distribution and and Reported Treatment or Prophylaxis Failures or True Reported Treatment or Prophylaxis Failures or True
Resistance, 2004Resistance, 2004
Source: WHO RBM Department, 2004
Vivax resistance to CQ confirmed inGuyana, Indonesia and Peru
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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
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The choice of artemisinin combination therapy (ACT)
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.
Combinations which have been evaluated:
piperaquineartemisinin +mefloquine
artesunate +
piperaquinedihydroartemisinin +mefloquine
lumefantrineartemether +mefloquine
naphthoquine
chloroquine
amodiaquine
sulfadoxine-pyrimaethaminine
mefloquine
proguanil-dapsone
chlorproguanil-dapsone
atovaquone-proguanil
clindamycin
tetracycline
doxycycline
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Response to increasing resistance Combination therapies recommended by WHO
• Artesunate + amodiaquine
• Artemether/lumefantrine
• Artesunate + SP
• Artesunate + mefloquine
FDC
WHO Technical Consultation on “Antimalarial Combination Therapy” – April 2001
ACTs
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Prevention
Drug prophylaxischloroquine: 0.3g once a weekdoxycycline
Kill mosquito Vaccination
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TOGETHER WE CAN BEAT MALARIA
THANK YOU FOR LISTENING