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Malaria

Parasitology Department
Medical Faculty of USU
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Malaria

General
Caused by obligate intracellular protozoan of the
phylum Apicomplexa
Causative organisms are vectored primarily by
female Anopheles mosquito, belong to the genera
Plasmodium
Complex life cycle, involving both sexual and asexual
phases
Produces febrile hemolytic anemias, resembles to
babesiosis
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Malaria

Distribution
The agents are four species of the genus
Plasmodium: P. vivax, P. ovale, P. malariae, and P.
falciparum
P. vivax accounts for the vast majority of malarial
infection, because o/t wide distribution o/t parasite
P. vivax is the only one that extends through tropical,
subtropical, and temperate regions

Malaria

Distribution

P. falciparum, which causes falciparum malaria,


is confined to the tropics and subtropics, and is
probably the most lethal form of malaria
Pockets of P. malariae infection are distributed
throughout the tropics and subtropics
P. ovale is primarily confined to tropical West
Africa, South America, and Asia

Malaria

Epidemiology

Malaria remains the worlds most


notorious tropical parasitic disease,
threatening some 2,400 million people
40% of the world population
WHO estimates 300-500 million new
cases and over 1 million deaths each
year

Malaria

Epidemiology

The risk of infection is determined by the


number and species of mosquito present
in a given areas as well as the climate
and geography
Contributions come from: seasons,
agricultural activity, populations shifts,
urbanization, deforestation, and forced
irrigation
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Malaria

Pathology

In all cases, once acquired, the patient


remains asymptomatic for more than a
week while the parasite goes to the
exoerythrocytic cycle in the liver
The clinical incubation period varies by
species
The onset of clinical disease may be non
specific prodromal symptoms
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Malaria

Malarial paroxysm
The release of merozoits from ruptured RBCs
triggers the malarial paroxysm
Patients experience a period of shaking chills
or rigor for 10-15 minutes
Followed by 2-6 hours of fever, body aches and
disorientation
As the fever subsides, the patient starts to
sweat profusely and returns to normal until the
onset o/t next paroxysm
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Malaria

Malarial paroxysm

After several erythrocytic cycles, the


episodes become synchronous and
develop a 48 or 72 hour periodicity,
depending on the species of parasite

Malaria

Pathology

The principal clinical symptoms of


malaria are anemia and splenomegaly
Anemia is caused by the direct lysis of
infected RBCs during the erythrocytic
cycle or by splenic removal of infected
antibody-coated red cell. RBC production
may also be diminished because of bone
marrow suppression
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Malaria

Vivax Malaria

The incubation period ranges from 10-17


days and may be followed by a series of
prodromal, flu-like symptoms before the
organism is seen in the peripheral blood
In early infection, paroxysm may not be
synchronous. Later, the regular 48 hour
periodicity is established

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Malaria

Vivax Malaria

The three day interval between clinical


episodes gave P. vivax the name benign
tertian malaria
P. vivax only invades reticulocytes (young
RBCs) which constitute only about 2% of
RBC population
Untreated primary attacks may persist
for 3 wks to 2 months
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Malaria

Vivax Malaria

Hypnozoits that lay dormant in liver cells


are responsible for relapses months to
years following the initial infection
Vivax malaria generally subsides
spontaneously

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Malaria

Vivax Malaria

Prognosis may depend on the presence


of any intercurrent infections or the
patients prior state of health
Rapid diagnosis and treatment produces
excellent results
Complications are rare

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Malaria

Ovale Malaria

Widely distributed throughout tropical


Africa, heavy concentration in coastal
West Africa
Clinically is remarkably similar to P.
vivax, the asexual cycle approximates 48
hours (tertian)
The parasite only invades reticulocytes

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Malaria

Ovale Malaria

The initial attacks last 2-3 wks and often


end with spontaneous recovery within
12-20 months
Prone to relapse, but seldom occurs after
one year

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Malaria

Malariae Malaria

Clinical incubation period is 18-40 days


Asexual cycle takes 72 hour interval
(quartan malaria)
The merozoits predominantly invade
mature RBCs

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Malaria

Malariae Malaria

Untreated primary attack may last 3-24


wks
Hypnozoiites are not produced
The initial infection may end in
spontaneous recovery or patients may
experience chronic low-grade
parasitemia leading to recrudescence
(reoccurrence) for 20 years
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Malaria

Falciparum Malaria

It is now fairly limited to the tropics and


subtropics
Typically produces the greatest
morbidity and mortality of all the
Plasmodium species
It is so called malignant tertian malaria

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Malaria

Falciparum Malaria

Schizogony generally occurs In the


capillaries and blood sinuses of internal
organs (spleen, liver, bone marrow) rather
than in the peripheral blood
Infected RBCs plug small vessels, leading to
ischemia and complications
Only early trophozoits and gametocytes are
seen in peripheral blood smears
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Malaria

Falciparum Malaria

P. falciparum invades RBCs of all ages


without discrimination, and the parasitemia
affects a high percentage of available cells
The degree of anemia can be quite severe
Clinical incubation period is 8-12 days
Cyclic paroxysms are established at 36-48
hour intervals

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Malaria

Falciparum Malaria

Hipnozoites are not produced and true


relapses do not occur
Untreated primary attack may last 2-3
wks, but may be marked by a variety of
complications, coma, or even death
Recrudescence can occur, but is seldom
seen after a year

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Malaria

Falciparum Malaria

Complications are generally caused by


the obstruction of capillaries by
parasitized RBCs and/ RBC debris
The symptoms vary with the level of
hypoxia and the organ involved
Anemia is a common and often severe
consequence of heavy parasitemia

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Malaria

Falciparum Malaria
Renal complications, e.g. glomerulonephritis,
nephrotic syndrome, and renal failure
Cerebral malaria is the most serious
complication, may lead to coma and death
Blackwater fever is rare, but it is brought on by
sudden intravascular hemolysis, marked with
hemoglobinuria

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Malaria

Diagnosis

Thick and thin Giemsa stained peripheral


blood smears are the specimens of
choice
The smear has 85-95% sensitivity and
95-100% specificity compares to PCR
test, but it requires longer time and well
experienced analysts

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Malaria

Diagnosis

All asexual stages, including


gametocytes, may be found in the
peripheral blood smears of P. vivax, P.
ovale, and P. malariae
In P. falciparum infections, only ring
forms and gametocytes are found

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Malaria

Diagnosis

QBC malaria test gives faster result than


the conventional, only the sensitivity and
specificity are lower, and it requires
particular tools (e.g. fluorescent
microscope, capillary tubes, and
centrifuge machine)

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Malaria

Diagnosis
Rapid tests are available now to detect
parasite protein in peripheral vessels
(histidine rich protein II)
Immunochromatographic test to detect
plasmodium lactate dehydrogenase (pLDH)
The two latest test have equal sensitivity and
specificity with the conventional, only the
results will drop to 30-70% if parasitemia is
below 100/l blood
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Malaria

Treatment
Classification of antimalarial drugs is based on
the antimalaria activities and pharmacological
structure
Due to antimalaria activities:
1.
Tissue schizontocides for causal prophylaxis:
theoretically not practical; pyrimethamine and
primaquine
2.
Tissue schizontocides for preventing relaps:
works in hypnozoit phase; pyrimethamine and
primaquine
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Malaria

Treatment
3. Blood schizontocides, which are the most important:
chloroquine, quinine, mefloquine, halofantrine,
pyrimethamine, sulfadoxine, sulfones, tetracycline,
etc
4. Gametocides: chloroquine and quinine is effective
for P. vivax and P. malariae, primaquine is effective
for all species
5. Sporontocides: inhibit the development of oocyst in
mosquito; primaquine and chloroguanide
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Malaria
Treatment

The used of ACT ( Aretemisinin Combination


Therapy) as the 1st line therapy for all region in
Indonesia & ART (Artesunate) for severe
malaria.

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1995-2000 Mono therapy


2001-2003 Combo Therapy with
Old Drugs
2005

Combo Therapy with


New Drugs (ACT)
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Kegagalan Pengobatan Dini


( ETF = Early Treatment Failure)

-Berkembangnya menjadi malaria berat pada hari H1,


H2, H3 disertai parasitemia
-Parasitemia pada H3 dengan temperatur
aksiler>37.5C
-Parasitemia H2 > H0
-Parasitemia H3 25% H0

Kegagalan Pengobatan Kasep


(LCF = Late Clinical &
Parasitological Failure)

- Berkembangnya tanda bahaya malaria berat setelah


H3 dan parasitemia ( jenis parasit = H0)
-Parasitemia dan temp. aksiler >37.5C pada H4 - H28

(LPF = Late Parasitological Failure) - Parasitemia H7, H14, H21, dan H28 ( Parasit = H0)

Respon Klinis & Parasitologis


Adekuat
(ACPR = Adequte Clinical &
Parasitological Response)

- Tidak ada parasitemia sampai H28 dengan abaikan


temp. aksiler, tidak sesuai dengan kriteria ETF/
LCF/LPF.
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-Klinis memburuk
-- Parasit > 25 %
-- Parasit +, Temp > 37.5
Klinis
Memburuk

Hasil
Mal +
H-2

H0
H-1

Datang
RS/Dr

- Klinis
- memburuk
-- Parasit +

H14

H4
H3

H5

H6

-Klinis memburuk

H21

H7

Mulai
Obat

E.T.F = G.O.Dini

- memburuk
-- Parasit +

-Klinis memburuk
-- Parasit +,
-Temp > 37.5

H2
H1

- Klinis

H28

- Klinis
-Klinis memburuk
-- Parasit +, Temp > 37.5

- memburuk
-- Parasit +

- Klinis
- memburuk
-- Parasit +

L.T.F = G.O. Lambat

MONITORING RESPONS DI POLI/ DOKTER


PRAKTEK

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Kombinasi ACT

Resisten obat pasangan belum terjadi


Pasangan obat mempunyai half-life panjang (> 4 hr)
Artemisinin membunuh bentuk asexual dgn cepat;
pasangan obat membersihkan parasit lainnya
Ditolerensi baik, toksisitas rendah
Artemisinin memiliki efek spectrum luas ( termasuk
membunuh gametosit)
Bila mungkin dosis tetap (Fixed dose )
Diproduksi secara standar Good Manufacturing
Practice (GMP)
Murah
Supply obat cukup
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Current ACT options I


Artesunate + Amodiaquine

Keuntungan :

Kemasan terpisah untuk program Depkes


Kemasan Blister tersedia di apotik
Ditolerensi baik
Tidak terlalu mahal ( Rp. 40.000/ treatment )

Kerugian:
Tablet banyak selama 3 hari : masalah kepatuhan
Fixed dose combination diperkirakan 2006-07
Diwaspadai cross-resistance terhadap chloroquine

28 day efficacy of AQ/ATS3 in African studies only 68-85%


28 day efficacy of AQ/ATS3 in Lampung only 76% (Setyaningrum
et al)

Supply: program depkes dan jual bebas

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ARTESDIAQUINE

ARSUAMOON

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INDIKASI A.C.T

Slide harus positif/ tes cepat +


Malaria Falciparum tanpa komplikasi
dari daerah terbukti resisten CQ3
Malaria setelah pengobatan terbukti
resisten obat

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DOSIS ARTESDIAQUINE
Obat/Umur

Hari

H1
H2
H3
Total tablet
Amodiaquine
H1
(200mg)
H2
H3
Total tablet
Artesunate
( 50 mg)

1-5 th

5-10th

10-15th

>15th

1
1
1
3
1

2
2
2
6
1
1
1
4

3
3
3
9
2
2
1
6

4
4
4
12
3
3
1
7-8
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PENGOBATAN MALARIA KLINIS


( tanpa hasil parasitologik )

OBAT NON-ACT
Monoterapi ( CQ3/ SP1/ Q7 )
Kombinasi :
SP + CQ
Quinine + Doxy/ Tetrasiklin
Qunine + Clindamycin
Quinine + SP
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Malaria

Treatment
The treatment of chloroquine-sensitive P. falciparum

No

Drug

Single dose tablet due to age of patient

Chlor

<1

Prim

2.

Chlor

3.

Chlor

1.

1-4

5-9

10-14

>15

3-4

2-3

3-4

2
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Malaria

Treatment
Primaquine
Causal prophylaxis activity, destroys preerythtocytic
parasites
Dose 0.5mg/kg base (max 30mg) since 1-2 days
before entering the area to 2-7 days after leaving
Artemisinin
Rapid onset in all malaria cases
Available in Indonesia with the name Maltron
(artemether), each tablet contains 50mg base
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Malaria

Treatment
Mefloquine
Drug of choice to prevent malaria in chloroquine
resistant areas
Contraindication: heart arrhythmia, history of
psychic disorder (psychotic, anxiety)
Doxycycline
To prevent malaria in chloroquine resistant areas
Contraindication: children < 8 yrs, pregnant and
gestation women
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Malaria

Treatment
The treatment of chloroquine-resistant patients:
Quinine sulfate
Malarone (combination of atovaquone and
proguanil)
Combination of atovaquone and doxycycline
Mefloquine
Halofantrine
Artemisinin
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Malaria

Treatment
The treatment of P. vivax, P. ovale, and P. malariae:
No.
1.

Drugs
Chlor
Prim

2.

Chlor
Prim

Single dose tablet according to age


<1

1-4

5-9

10-14

>15

3-4

3-4

Chlor

Prim

4.

Prim

5.

Prim

3.

1
1

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Malaria

Treatment

Treatment of malaria in pregnant women:


Chloroquine, and quinine or quinindine with
clindamycin are safe
Doxycyclin, primaquine, mefloquine,
halofantrin are prohibited
Artemisinin is only safe in the 2 nd and 3rd
trimester
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Malaria

Prevention

The key to the control and prevention of


malaria:

Long-term mosquito abatement


Human treatment
Prophylaxis

Early diagnosis and treatment of existing


cases is fundamental to breaking the humanmosquito-human cycle
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Malaria

Prevention

To reduce the risk of infection:


Wearing long-sleeve protective clothing and
using repellant (with DEET)
Mosquito nets soaked in pyrethrum/permethrin
1%
Insecticides and larvicides
Not wearing dark-color clothes and perfumes at
night

Screen and protect the donor blood supply


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Malaria

References
Heelan, J. S., Ingersoll, F. W.: Blood and Tissue Sporozoa
in Essentials of Human Parasitology, Delmar Thomson
Learning, US, 2002
Pasaribu, S.: Malaria Pencegahan dan Pengobatan
Terkini, Nusantara 37 (I) 2004, Balai Penerbitan FK USU
Peters, W., Pasvol, G.: Arthropod-borne Infections in
Tropical Medicine and Parasitology, 5th ed., Mosby,
London, 2001
Harijanto, Paul.: Tata Laksana Malaria Baru 2005
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Thank you

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