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Update of Management
HENDRATA
Dvision of Infectious and Tropical Disease
Departement of Internal Medicine
UDAYANA School Medicine
Sanglah General Hospital
Denpasar BALI
Malaria Infection
• Agent
– P. Vivak
– P. Ovale
– P. malariae
– P. falciparum
– P. knowlesi
• Vector
– Anopheles sp
Malaria Endemicity in Indonesia
2008
Hypnozoites
Exo- (for P. vivax and
erythrocytic P. ovale)
H Gametocytes
(hepatic) cycle
U
M
A Erythrocytic
Cycle
N
Schizogony
Patogenesis
• Invasion of red cell
• Cytoadherence
– Process whereby mature infected cells specifically
bind to endothelial cells in postcapillary venule
• Rosetting
– Red cell containing the more mature stages of
parasite bind uninfected red cells to their surface
• Parasite toxin and cytokines
– TNF α, IF gamma, IL-1,IL-6
– GPI
Types of Infections
• Recrudescence
– exacerbation of persistent undetectable parasitemia,
due to survival of erythrocytic forms, no exo-
erythrocytic cycle (P.f., P.m.)
• Relapse
– reactivation of hypnozoites forms of parasite in liver,
separate from previous infection with same species
(P.v. and P.o.)
• Recurrence or reinfection
– exo-erythrocytic forms infect erythrocytes, separate
from previous infection (all species)
• Can not always differentiate recrudescence from
reinfection
Clinical presentation
Varies in severity and course:
• Parasite factors
– Species and strain of parasite
– Geographic origin of parasite
– Size of inoculum of parasite
• Host factors
– Age
– Immune status
– General health condition and nutritional status
– Chemoprophylaxis or chemotherapy use
• Mode of transmission
– Mosquito
– Blood borne, no hepatic phase (transplacental,
needle stick, transfusion, organ donation/transplant)
Clinical presentation
Symptoms and sign are non specific
• Early symptoms
– Headache
– Malaise
– Fatigue
– Nausea
– Muscular pains
– Slight diarrhea
– Slight fever, usually not intermittent
• Could mistake for influenza or gastrointestinal
infection
Clinical presentation
• Signs
– Anemia
– Thrombocytopenia
– Jaundice
– Hepatosplenomegaly
– respiratory distress syndrome
– renal dysfunction
– Hypoglycemia
– Mental status changes
– Tropical splenomegaly syndrome
Malarial Paroxysm
• Paroxysm
– Cold stage – rigors (15 minute – 1 hours)
– Hot stage – Max temp can reach 40-41o C,
splenomegaly easily palpable (≥ 2 hours)
– Sweating stage
– Lasts 8-12 hours, start between midnight and
midday
• Periodicity
– Days 1 and 3 for P.v., P.o., (and P.f.) - tertian
– Usually persistent fever or daily paroxyms for P.f.
– Days 1 and 4 for P.m. - quartian
Severe malaria (1)
• Cerebral malaria
– Coma with peripheral parasitemia and the other
cause of encephalopathy excluded
• Generalized convulsions
• Severe normocytic anemia
– Normocytic anemia with Hb < 5 g/dl, < 15 %
hematocrit, in presence of parasitemia > 10.000 /uL
• Hypoglycemia
– Whole blood glucose < 40 mg/dl (2.2 mmol/l)
• Metabolic acidosis with respiratory distress
– Acidosis (BE ≤ 12) or acidemia (pH < 7.3)
• Fluid and electrolyte disturbance
– Hypovolaemia dehydration
WHO,2006
Severe malaria (2)
• Acute renal failure
– Urine output less than 400 ml/24 h and a serum creatinine > 3.0
mg/dl
• Acute Respiratory Distress Syndrome
• Circulatory collapse, shock, septicaemia (“algid malaria”)
– Systolic blood pressure less than 70 mmHg or core skin
temperature difference > 10C
• Jaundice
– Icteric (serum bilirubin > 3 mg%)
• Haemoglobinuria (black water fever)
• High fever
– Rectal temperature > 400C
• Hyperparasitaemia
– High parasite densities (>5%) in non-immune subjects
WHO,2006
Severe Vivax malaria
• Although benign malaria, reported also
causing severe and debilitating illness.
• Severe vivax manifestation : cerebral
malaria, severe anaemia, severe
thrombocytopenia, pancytopenia,
jaundice, spleen rupture, acute renal
failure and acute respiratory distress
syndrome
Diagnosis
• Clinical presentations
• Microscopic examination
– Thick blood film
– Thin blood film
• MRDT (Rapid diagnostic test for Malaria)
– Serologic
• Antibody detected:
– indirect immunofluorescence test, haemaggutination/latex
agglutination test, enzyme linked immunoassay (ELISA)
• Antigen detected:
– radioimmunoassay, ELIZA
• PCR
Management
• Falciparum or
non Falciparum
• Uncomplicated or
Complicated/Severe
• Supportive
– Nutrition
– Fluid and electrolytes
balance
– Antipyretic, etc
• Causal (antimalarial)
– Chloroquine
– Primakuine
– Quinine
– Artemesinin derivat
• Treatment for complication
– Depend of kind of the
complication
Treatment of uncomplicated vivax
• Choice: Chloroquine 25 mg base/KgBW divided over 3
days, combined with Primaquine 0.25 mg base/KgBW,
taken with food once daily for 14 days (O,E)
• Amodiaquine (30 mg base/KgBW divided over 3 days as
10 mg/KgBW single daily doses) combined with
Primaquine should be given for chloroquine-resistant
vivax malaria (O,E)
• Where ACT has been adopted as the first-line treatment
for P.falciparum malaria, it may also be used for P vivax
in combination with primaquine.
AS + SP is the exception as it will not be effective
againts P. vivax (O,E)
ARTEMETER
•only I.M ,
•dose 1,6 mg/kg BW
Adjustment of dosing in organ
disfunction
• The dosage of artemisinin derivates does not
need adjustment in vital organ dysfunction
• The dosage of Quinine should be reduced by
one-third after 48 hours if:
– Acute kidney injury
– Hepatic dysfunction
– No clinical improvement after 48 hours of treatment
The dosage adjustments are not necessary if patients
are receiving either hemodialysis or hemofiltration
Follow on treatment
• After patient can tolerate oral therapy
change to oral antimalarial
• Continue with
– Same medicine orally as given parentrally to
complete a full 7 days of treatment
– Added with doxycycline for 7 days
– If pregnant and children: doxycycline
substituted by clindamycin
Treatment of severe falciparum malaria in
pregnant women
• Use the parentral antimalarial treatment
locally available for severe malaria in full
doses.
• First trimester, until more evidence
become available, both artesunate and
quinine may be considered as option
• Where available, artesunate is the first,
and artemether the second option in the
second and third trimester
Basis of decision:expert opinion (Level E)
Response of treatment
Response
Early Treatment Failure One or more
•Sign and symptoms severe
malaria
•Parasetemia at D2 ≥ D0
•Parasetemia at D3 ≥ 25% D0
Late Treatment Failure One or more condition at H4-
H28
•Sign and symptoms of severe
malaria after D3
•Parasetemia at D7/D14/D21/D28
(type of parasite = D0)
Adequte Clinical •No fullfill criteria for ETF and LTF
Respon
Pre-referral Treatment The risk
of death from severe malaria is greatest in the first 24
hours
Urgent Investigation:
Thick & Thin blood film and Malaria rapid antigen test, CBC,LFT, RFT, Blood
glucose
Blood tests show: