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MALARIA

Dr. DWI HANDAYANI

MALARIA
Reference
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Parasitology Protozoology and Helmintology Basic Clinical Parsitology: Brown & Belding K.D. Chatterjee Clinical Parasitology: Paul Chester Beaver c.s. The immunology of Parasitic infection omar o. Barriga Faundation of Parasitology Gerald D. Schmidt & L.S. ROBERT Atlas of Medical Helmintology & Parasitology: Jeffrey & leach Modern Parasitology : Edited by F.E.G. Cox Medical Parasitology, Apractical Approach Edited by S. H. Gillespie and P. M. Hawkey Perubahan Radidkal dalam Pengobatan Malaria di Indonesia P.N. Harijanto. Cermin Dunia Kedokteran, 2006 Internet

Classification of malarial parasite


Phylum Subphylum Class Subclass Family Genes
Species

Protozoa Sporozoa Telosporidea Haemosporidia Plasmodiidae Plasmodium


P. vivax P. malariae P. falciparum P. ovale

Monkey plasmodium
P. cynomolgi

P. knowlesi

Morphology: - Chromatin - Cytoplasm - Pigment - Granula

Plasmodium vivax

Plasmodium falciparum

Plasmodium malariae Ring form; band form; schizont

Plasmodium ovale

Physiology
Latent period in the body : - P. falciparum : shortest - P. malariae : longest Plasmodium: Hb Iron porphyrin hematin + Globin Hematin= ferrihemic acid=pigment malaria

For survival the malarial parasites need: CHO; PROTEIN; FAT


Besides they also need: Methionin Riboflavin Para-aminobenzoic acid Panthotenic acid Vit C

Life cycle
- Intrinsic phase: in the vertebrate host, asexual schizogony
- Extrinsic phase:

in the female anopheles mosquito, sexual sporogony

Life cycle of malarial parasites

Life cycle of P. vivax or P.ovale


Man In the liver
Hypnozoite
Schizont
sporozoite

Female anopheles

merozoite

oocyst

in RBC

TROPHOZOITE

SCHIZONT

MEROZOITE

ookinete

MAKROGAMETOCYTE

makrogamete

zygote

MIKROGAMETOCYTE

mikrogamete

Epidemiology of malaria

60o

Equator 30o

2,770 m above sea level Cochabamba 400 m bellow Dead sea basin

Impact of malaria
Malaria causes about 350-500 million infections in humans and approximately one to three million deaths annually. The vast majority of cases occur in children under the age of 5. Pregnant women are also especially vulnerable.

(Epidemiology) anopheles mosquitoes


Vectors in indonesia: Anopheles annularis Anopheles vagus Anopheles barbirostris Anopheles aconitus Anopheles sundaicus Anopheles maculatus Anopheles balabacensis Anopheles punctularis Anopheles subpictus Ano;heles indefinitus

(Epidemiology)
Endemic : connotes natural transmission in an area so that there are autochthonous, locally contracted cases Imported malaria: is acquired outside the area Introduced malaria : cases derived from Imported malaria Sporadic : cases are few and scattered

Malaria endemicity:
The prevailing frequency and intensity of endemic malaria. Classification of endemicity: Based on spleen index (%) of children in age group 2-9, and the spleen rate of adult

(Epidemiology)
Classification of endemicity:
Hypoendemic malaria: spleen rate in age group 2-9 10% 2. Mesoendemic malaria : 2-9: 11-50% 3. Hyperendemic malaria : 2- 9 > 50% and adult spleen rate 4. Holoendemic malaria : spleen rate in age group 2-9 > 75% but adult tolerance high and adult spleen rate
1.

Mode of infections: 1. Bitten by female anopheles 2. Congenital 3. Transfusion 4. Organ transplantation


Pathology 1. Vascular blockade of vascular by parasistized rbc. 2. Anoxia (organ) 3. Deposition of pigments

Incubation period:
P malariae P. falciparum P. ovale P. vivax : 12-14 days : 10-12 days : 10-12 days : 14-17 days

Symptomatology
1.

The febrile paroxysm may be divided into 3 clinical stages: - cold stage (15-16 minutes) - host stage (about 2 hours: 39-40o C) - sweating stage (about 1 hour)

Secondary anemia 3. splenomegaly


2.

The attack of paroxysm


P. vivax and P. ovale : 48 hours P. falciparum : 24-48 (36-48) hours P. malariaae : 72 hours

Diagnosis
Thick film (DDR Thin film Q.B.C. (Quantitative Buffy Coat) I.R.M.A. (Immunoradiometric assay) Elisa for Ag p. falcliparum (HRP-2 = histidine Rich Protlein-2) 6. RNA probe 7. DNA Hybridization 8. Rapid Manuel test (P.falciparum)HRP-II also available for vivax
1. 2. 3. 4. 5.

(Diagnosis of malaria)
9. Indirect fluorescence Assay (IFA) 10. Polymerase Chain Reaction (PCR)

Pernicious manifestation
Warning signs: asexual parasitemia 5%, 10 % with multiple rings in red cells and schizonts in peripheral blood

Pernicious manifestation:
Cerebral malaria Malaria with jaundice Diarrhoea, dysentery Renal failure Pulmonary edema Black water fever Algid malaria, shock Hyperpyrexia

Algic malaria
A condition analogous to cerebral malaria, except that the gut and other abdominal viscera are involved. The skin is cold and clammy, but internal temperature is high.

(Algic malaria)
Two types: Gastric Dysenteric : with persistent vomiting : with bloody, diarrheic stools containing enormous numbers of parasites.

Definition of severe malaria (WH0)


One or more of the following criteria + the presence of asexual parasitaemia defines severe malaria
1. 2. 3. 4.

Cerebral malaria/unarousable coma Severe anaemia Renal failure Pulmonary oedema/adult respiratory distress syndrome (ARDS)

[Definition of severe malaria (WH0)]


5

6
7 8 9

10

Hypoglycaemia Hypotension/shock Bleeding/disseminated intravascular coagulation (DIC) Convulsion Acidosis/ Acidaemia Macroscopic haemoglobinuria

Pathophysiology of Cerebral malaria:


It is exactly not known Proposed hypotheses: 1. Permeability hypothesis (Maegraith and fletcher) 2. Toxic/cytokine hypothesis 3. Mechanical hypothesis

Black water fever


Haemoglobinuria fever Nausia & vomitus Icterus Pamaquine quinine (qinghousu) Death due to Renal failure

Treatment
1. Non-specific

treatment:

symptomatic and supportive measures according to the clinical manifestation 2. Specific treatment: Blood schizontocide: - Chloroquine - sulfadoxine & pyrimethamine (SP) - quinine; Mefloquine - Artemisinin/Qinghausu (artesunate; artemeter; dihidroartemisinin) - Artemisinin based combination therapy (ACT): e.g.: Artesdiaquine (Artesunate 50 mg + amodiaquine 200 mg). - Non Artemisinin based bcombination therapy (NON-ACT): e.g. Quinine + SP Chloroquine + teteracycline /doxicycline Gametocytocide : Primaquine

Chemoprophylaxis
Chloroquine: 300 mg base weekly Sulfadoxine 1 g + Pyrimethamine 50 mg every two weeks Sulfadoxine .1.5 g + Pyrimethamine 70 mg every four weeks

Mefloquine: 5 mg/kg BB/weekly


(250 mg/tablet base)

Suppressive treatment:
Chloroquine: 0.5 g weekly

Early treatment failure:


One or two condition occur as bellow within the first 3 days of treatment Parasitemia with complication of severe malaria on day 1, 2 and 3. Parasitemia on day 2 > that on day 0 Parasit count on day 3 > 25% of day 0 Or the axial temperature: > 37.5

Late treatment failure:


if the following conditions occur on day 4 28, divided into 2 sub group:
1.

Late Clinical (and parasitological) Failure (LCF) - Parasitemia (the same species with that of day 0) complicated with severe malaria after day 3. - The axial temperature > 37 C with parasitemia between day 4 - 28.

Late treatment failure


Late Parasitological Failure (LPF) Parasitemia (the same species with day 0) on day 7, 14 or 28 without rising of the axial temperature (< 37 C)

Resistance: The ability of a parasite strain to survive and /or to multiply despite the administration and absorption of a drug given in doses equal to or higher than those usually recommended but within the limits of tolerance of the subject.

Resistance of asexual parasites (P. falciparum) to schizontocidal drugs (4-aminoquinolines)

Immunologi of malaria
innate Plasmodium: host specific
In the liver of man:
Well developed

P. vivax
In liver of chimpanse:
Not develop

The liver of mouse: 1%

P. berghei
In the liver of a tree rodent: 50%

The immunity of malaria


The combination of those mechanisms which: 1. Prevent infection 2. Prevent reinfection 3. Prevent super infection With the outcome of: Destruction of the malarial parasites Hindrance of their multiplication, Modification of their effects and Helping specifically for the repairing of tissues.

(Immunity)
P. falciparum : infection disappears within a year P. vivax P. Malariae years : 1-1 years. : infection persists until 20-30

(Immunity of malaria)
1. innate:

Such as: - G6PD deficiency - Duffy factor negative - Sickle cell anemia - Thallasemia Hb & Hb E - Hb foetus of human - ATP deficiency

(immunity of malaria)
2. Acquired

- Passive - Active: 1. concomitant 2. residual

(Immunity of malaria):
Non specific R ES 2. Specific: Gamma globulin lysin Agglutinin Precipitin Opsonin Ablastin Complement-fixing Cytoplasm-modifying
1.

In high endemic area of malaria:


infant<4 month
Relative resistant to malaria

4 months- 3 10 -15 years adult years High Low parasite Low parasite parasite rate rate rate

Receptor : glycoprotein
Merozoite

Duffy factor Genotype: Fy, Fy


a b

RBC

Premunision: a specific immune response clinical recovery & resistant to super infection.
Tolerant Immunities: - species specific - strain specific

Macrophage

P. falciparum

Low level High level

TNF
Patologi
Protection Inhibition of parasites in: The liver & -Dyserythropoisis Cytoadherence --Erythro phagocytosis Adherence of parasitized rbc to vascular Anemia endothelium Clinical manfestations: Such as:

RBC

- Headache
- Fever - Chill etc.