Pugud SamodroBag/SMF Ilmu Penyakit Dalam

FKIK Unsoed/ RSUD Prof Margono SoekarjoPurwokerto

What is Malaria? Parasitic infection of human red blood

cells 4 species can infect humans

Plasmodium falciparumPlasmodium vivaxPlasmodium malariaePlasmodium 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

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

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

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

Pathology

Anemia:P. Vivax - retiform RBCP. Malariae - mature RBCP. Falciparum - every RBC

Prolifeation of mononuclear phagocytehepatomegalysplenomegaly

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 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

Clinical manifestation

Signsanemiasplenomegalyhepatomegaly, 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, deliriumRelapse: 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 cellsAssociated with increased mortality

Cerebral malariaDamages brain and other vital organsFatality 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

Gametocyte

Trophozoite

Schizont

Plasmodium malariae

Ring stage

Gametocyte

Trophozoite

Schizont

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

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 )

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

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

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

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

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)

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

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

Prevention

Drug prophylaxischloroquine: 0.3g once a weekdoxycycline

Kill mosquito Vaccination

TOGETHER WE CAN BEAT MALARIA

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