Malaria

Lambok Siahaan
Spesies Plasmodium

 Plasmodium falciparum
 Plasmodium vivax
 Plasmodium malariae
 Plasmodium ovale
 Plasmodium knowlesi

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 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

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 Alteration of Host Cells

• A variety of structural changes, which alter its function,

appearance or antigenicity.
• These alterations are a consequence of parasite growth
• Advantage to the parasite (e.g. increased membrane
permeability, increased selective intake of nutrients, or
escape from immunity by sequestration).
• The nature of the alterations induced are variable from
one species to another.
 Alteration of Host Cells
1. A visible change of shape and
reduced deformability
2. The presence of electron-
dense protrusions or 'knobs‘
3. The presence of small
depressions, or "caveolae", at
the surface of the red cell,
connected by a network of
small vesicles and clefts in P.
vivax and P. ovale
 Alteration of Host Cells
4. The cytoadherence to endothelial cells
5. The adherence to normal erythrocytes
("rosetting") or to other infected
erythrocytes ("auto-agglutination“ or
clumping)
6. The presence of new metabolic
channels; evidence of new parasite-
specific antigens associated with the red
cell membrane
Pathogenesis

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Hill, Nature Reviews/Immunology, 2006.
Hemozoin

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 Parameter epidemiologi
–Parasite rate (PR): persentase penduduk yang
darahnya megandung parasit malaria pada saat
tertentu
–Spleen rate (SR): ditentukan berdasarkan klasifikasi
Hacket

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 Parameter epidemiologi
–Derajat endemisitas malaria pada suatu daerah
tertentu dapat diukur dengan mengetahui spleen
rate dari anak dan orang dewasa, yaitu:
– Hipoendemik : SR (anak 2-9 th) 0-10%
– Mesoendemik : SR (anak 2-9 th) 11-50%
– Hiperendemik : SR (anak 2-9 th) menetap di atas 50%
– Holoendemik : SR (anak 2-9 th) menetap di atas 75% (dewasa
25%)

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 Pathogenesis
Pathogenesis
Inflammatory
Chill, fever, sweat
responses
Toxic mediators
metabolic hypoglycaemia
disturbances

Bone Marrow Supression Anemia

Hemolysis
Phagocytosis renal failure
Splenomegaly Black water fever
Adhere to
+ Rosseting hepatomegaly
blood vessels
Cerebral malaria
Tissue hypoxia
Obstruct
Pulmonary edema
blood flow
Impaired
microcirculation DIC
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 Pathogenesis
• Related to erythrocytic infection by the asexual stages
• Gametocytes not involve in pathogenesis
• Pathology is associated with:
Haemolysis
- Direct invasion & rupture of RBC during erythrocytic cycle
- Increased osmotic fragility of RBC

increased adhesiveness of infected RBC

- Increases with the maturity of the parasite (schizont > trophozoite)
- Knob theory

release of pyrogens, toxin and cytokines

immunological responses
capillary permeability
tissue hypoxia
Severe anaemia - pathogenesis
• Erythrocyte destruction
during schizogony

• Erythrophagocytosis in
spleen
• Hypersplenism
• Immune mediated

Spleen
• Bone marrow suppression
• TNF/IL-10 ratio
• Reversible
 Immunologi Reaction

• Immunity is poorly understood , incomplete and is species

specific.

• Anti-disease immunity (parasitemia in the absence of fever and

other symptoms) is common, while anti-infection immunity
(ability to completely clear parasites after challenge
inoculation) is less common.

• Both antibody (against blood stages) and cell-mediated

immunity (against liver stages and blood stages) develop after
repeated infection.
 Immunity
Influenced by
– Genetics
– Age
– Health condition
– Pregnancy status
– Intensity of transmission in region
– Length of exposure
– Maintenance of exposure
 Immunity
Innate
– Red cell polymorphisms associated with some
protection
• Hemoglobin S sickle cell trait or disease
• Hemoglobin C and hemoglobin E
• Thalessemia – α and β
• Glucose – 6 – phosphate dehydrogenase deficiency
(G6PD)
– Red cell membrane changes
• Absence of certain Duffy coat antigens improves
resistance to P.v.
 Immunity
Acquired
– Transferred from mother to child
• 3-6 months protection
• Then children have increased susceptibility
– Increased susceptibility during early childhood
• Hyper- and holoendemic areas
– By age 5 attacks usually < frequent and severe
– Can have > parasite densities with fewer symptoms
• Meso- or hypoendemic areas
– Less transmission and repeated attacks
– May acquire partial immunity and be at higher risk
for symptomatic disease as adults
 Immunity
Acquired
– No complete immunity
• Can be parasitemic without clinical disease
– Need long period of exposure for induction
– May need continued exposure for maintenance
– Immunity can be unstable
• Can wane as one spends time outside endemic area
• Can change with movement to area with different
endemicity
• Decreases during pregnancy, risk improves with
increasing gravidity
Diagnosa Malaria

Laboratory Dx

Clinical Dx

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 Diagnosa Malaria
Tanda dan Gejala Klinis

• Anamnesis:
– Main symptoms: triad (not always found)
– Might be coincide with headache, nausea,
vomiting, diarrhea, myalgia
– History of visiting endemic area (1-4 weeks prior
to symptom)
– History of living in endemic area
– History of having malaria
– History of taking anti-malarial drugs
– History of blood transfussion
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 Diagnosa Malaria
Tanda dan Gejala Klinis

• Physical examination:
– Fever
– Anemic
– Hepatomegaly
– Splenomegaly
– With or without organ dysfunction in severe
malaria or malaria with complication
 Diagnosa Malaria
Laboratorium

• Blood film (microscopic) • RDT (Rapid Diagnostic Test)

– Gold standard – Dipstick
– Sensitivity 40 parasites/μl – Antigen detection:
• HRP-2 detection
• pLDH Ag
• PCR
• Pan-malaria Ag
– Sensitivity up to 4
parasites/μl – Sensitivity ±100 parasites/μl
Diagnosa Malaria
Mikroskopis

Thick blood film: 10μl

blood (3 drops)

Blood smear: 2μl blood

(1 drop)

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Prinsip Pengobatan Malaria
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

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 Pendekatan Terapi
• Terapi diberikan atas dasar hasil pemeriksaan
mikroskopis ataupun RDT
• Terapi kombinasi
• Terapi radikal
• Titik berat hasil adalah: kesembuhan klinis, parasite
clearance, dan tidak adanya penularan

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 STANDARD
PENGOBATAN MALARIA

Pf Malaria tanpa komplikasi: Prophylaxis

1. DHP + PQ1  Doxycycline
2. AMO3+ASU3+PQ1
3. QN7+DX7 +PQ1 Penanggulangan KLB(MBS/MFS)
 Pf Malaria:
Pvivax Malaria: DHP + PQ1
1. DHP + PQ14 AMO3+ASU3+PQ1
2. AMO3+ASU3+PQ14  Pv Malaria:
3. QN7+PQ14 DHP + PQ14
AMO3+ASU3+PQ14
 STANDARD
PENGOBATAN MALARIA
ANAK BALITA:
IBU HAMIL:
Pf Malaria tanpa komplikasi:
Pf Malaria tanpa komplikasi: 1. DHP + PQ1
 Trimester 1 : QN7. 2. ASU3 + AMO3 + PQ1.
 Trimester 2,3: AMO3+ASU3 3. QN7 + PQ.

Pvivax Malaria tanpa komplikasi: Pvivax Malaria tanpa komplikasi :

1. Trimester 1 : QN7 1. DHP + PQ14
2. Trimester 2&3 : ACT3 2. ACT3+PQ14
3. QN7+PQ14
BUMIL TAK DIBERI PQ dan DOXY
BAYI TAK DIBERI PQ.
BALITA TAK DIBERIKAN DOXY
 Faktor Yang Berpengaruh Terhadap
Kejadian Malaria

Endemicity
Resitency
Antimalaria
Spesies
Species
Insect Bite
Virulence
Mixed Infection

Immnunity
Genetic
Nutrient
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 STRATEGIES
Endemicity level Transmission Parasite rate Comment
(%)a
Hypoendemic Usually Mosquito population
Low: subperiodic or unstable; usually difficult to
malaria sporadic < 10% detect; serious epidemic may
occur
Mesoendemic Seasonal or periodic 11-50, Mosquito populations
depending fluctuate, detectable;
malaria following good rains
seasonal outbreaks occur;
on survey
some detectable immunity in
timing the population
Hyperendemic Intense transmission 51-75 Seasonal fluctuation in
(seasonal )each year malaria cases; severe
malaria sequelae in young children;
some immunity in adults
Holoendemic Transmission may >75 Mosquitoes detectable
occur throughout the throughout the year although
malaria
year with periods of with seasonal peaks; high
levels of anemia in very
high transmission
young children; immunity
seen in adults
 REFERENCE
Beaver, P.C., Jung, R.C. 1984. Clinical parasitology. 9th ed.
Philadelphia, Lea & Febringer. p.292-294; 345
Gillespie, S., Pearson, R.D. 2001. Principle and practice
of clinical parasitology.John Wiley & Son Ltd. p.124
Heelan, J. S., Ingersoll, F. W. 2002, Blood and Tissue
Sporozoa in Essentials of Human Parasitology,Delmar
Thomson Learning, US,
Peters, W., Pasvol, G. 2001, Arthropod-borne Infections
in Tropical Medicine and Parasitology, 5th ed., Mosby,
London
Schimidt, G.D., Roberts, L.S. 2005. Foundation of
parasitology. 7th ed. Mc Graw Hill. p. 118-119;136-137;
427-428; 458; 468-471
 Antidisease Antiparasite
immnunity immnunity

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 Daftar Penyakit Berdasarkan SKDI
• Malaria 4A
• Malaria serebral 3B
• Anemia hemolitik 3A
• Pneumonia, bronkopneumonia 4A
• Gastroenteritis (termasuk kolera, giardiasis) 4A
• Gangguan pembekuan darah (trombositopenia) 2

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 Daftar Masalah Berdasarkan SKDI
• Sakit kepala
• Pusing
• Kesemutan
• Batuk dan sesak
• Nyeri perut dan ulu hati
• Perut kembung
• Mual dan muntah
• Diare
• Lemah/letih/lesu
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 Daftar Masalah Berdasarkan SKDI
• Nafsu makan hilang
• Kelelahan
• Pucat
• Demam
• Mata kuning

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 Daftar Ketrampilan Klinis
Berdasarkan SKDI
• Identifikasi parasit 4A
• Persiapan dan pemeriksaan hitung jenis leukosit 4A
• Finger prick 4A
• Pemeriksaan darah rutin (Hb, Ht, Leukosit,
Trombosit) 4A
• Permintaan pemeriksaan imunologi berdasarkan
indikasi

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 Daftar Ketrampilan Klinis
Berdasarkan SKDI
• Pemeriksaan profil pembekuan (bleeding time,
clotting time) 4A
• Pemeriksaan Laju endap darah/kecepatan endap
darah (LED/KED) 4A
• Pengukuran suhu 4A
• Konsultasi terapi 4A

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