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MALARIA

Indah Lestari
Cases (per 1,000) by country, 2009

Estimated 300-500 million


clinical cases each year

WHO. World Malaria Report 2010


Epidemiology
The impact of malaria

• The World Malaria Report of 2012  in 2010, approximately 3.3


billion people were at risk of malaria around the world and 219
million cases are estimated to have occurredkills
approximately 660,000 people annually,  reduced by 47%
between 2000 and 2013

• Africa accounted for an estimated 47% (103 million) of global


malaria cases

• In South-East Asia, the second most affected part of the world,


India has the highest malaria burden, followed by Indonesia and
Myanmar.
Insidence (per 1,000) Indonesia 2008
ACEH 2,03 NTT 0
SUM-UT 8,15
KAL-BAR 3,23
SUM-BAR 2,58
RIAU 3,06 KAL-TENG 11,21
JAMBI 18,08 KAL-SEL 4,20
SUM-SEL 5,46
KAL-TIM 8,59
BENGKULU 22,96
SUL-UTARA 16,48
LAMPUNG 2,79
SUL- TENGAH 17,81
BANGKA BELITUNG 40,58
RIAU 13,32 SUL- SELATAN 1,51
DKI JAKARTA 0 SUL- TENGGARA 10,26
JAWA BARAT 0,58 GORONTALO 13,94
JAWA TENGAH 0,07 SUL- BARAT 11,98
D I YOGYAKARTA 0,03
MALUKU 39,65
JAWA TIMUR 0,71
MALUKU UTARA 51,42
BANTEN 0,03
BALI 0,17 IRIAN JAYA BARAT 84,74
NTB 21,85 PAPUA 167,47
What is malaria ?

• Malaria is a potentially serious disease caused by


parasites called PLASMODIA
• Plasmodia parasites are transmitted between humans by
the bite of an infected female ANOPHELES mosquito,
which can carry the parasites
Basic factors in malaria
transmission
Components of the Malaria Life Cycle
Sporogonic
cycle

Infective
Period
Mosquito bites
uninfected
person Mosquito Vector

Parasites visible
Human Host
Mosquito bites
gametocytemic Prepatent
person Period Symptom onset
Recovery

Incubation Period
Clinical Illness

Adapted from:
CDC
Hosts of malaria

• Human  Gorilla
• Bird  Chimpanzee
• Bat  Crab Eating
• Antelope Macaque
• Lizard  Orangutan
• African Great  Mosquito
Ape
Hosts of malaria

 Factors Inherent in Man


 Race
 Immunity
 Age
 Sex

 More susceptible population


 Young children
 Pregnant women
 Non-immunes
Pregnant women at high risk

• Pregnant women have an increased susceptibility to


contracting malarial infection because of changes in
their immune system related to the pregnancy

• Pregnant women more susceptible to P. falciparum


specifically because of placenta provides a novel
intervillous space for cytoadherence
Agents of malaria

All agents come from the protozoan Plasmodium genus.


 P. vivax  tertiana malariae
 P. malariae  quartana malariae
 P. ovale  benigna malariae
 P. knowlesi
 P. falciparum maligna/tropica
malariae

Protozoan cell
Vectors of malaria

• Anopheles flavirostris
• Anopheles litoralis
• Anopheles maculatus
• Anopheles mangyanus
• Anopheles balabacensis
Transmission
Life cycle of malaria parasites
Major symptoms of malaria
Sign and symptoms

Mild Early Symptoms


• Cold Stage (1-2 hours)
• Fever, Shaking, Chills
• Hot stage (3-4 hours) DINGIN DEMAM
– High fever(41.70C),
Headache, Nausea, APIREKSI KERINGAT
Vomiting, Dizziness,
Pain Delirium
• Sweating Stage (2-4 DI-DE-RI-TA
hours)
• Sweating(diaphoresis),
fall in temp.
The attacks periodicity

~ EVERY-DAY  FALCIPARUM
~ EVERY-OTHER-DAY  TERTIAN  PL. VIVAX & OVALE
~ EVERY-THIRD-DAY  QUARTIAN  PL. MALARIAE
~ TIRED BETWEEN ATTACKS, BUT FEELS WELL
~ AFTER THIS PRIMARY EPISODE, RECURRENCE ARE
COMMON, EACH SEPERATED BY A LATENT PERIOD
SUSTAINED FEVER
(KONTINYU)

< 1° C

SUHU NORMAL

JAM 6 12 18
GAMBARAN DEMAM TERTIANA

SUHU NORMAL

HARI 1 2 3
GAMBARAN DEMAM KUARTANA

SUHU NORMAL

HARI 1 2 3 4
Sign and symptoms

• Anemia • brain damage,


• Pallor, tiredness, coma (cerebral
shortness of malaria)
breath, fatigue • Hemoglobinuria
• Splenomegaly (black water fever)
• Hepatomegaly • hemolysis
• jaundice
Clinical diagnosis

Laboratory diagnosis: Parasite-based diagnosis


•Direct parasite demonstration
Microscopy - Blood smear
QBC method
•Antigen detection
RDTs: HRP-2, pLDH, Aldolase
Nucleic acid based methods – PCR, Real-time
PCR and LAMP…
•Indirect demonstration of parasite exposure
Antibody based methods: IFA, ELISA
Clinical diagnosis

• Rapid Diagnostic Tests


• Uses immunochromatographic methods to detect
Plasmodium specific antigens
Complication

1. CEREBRAL MALARIA:
- HEADACHE
- MENTAL DISTURBANCES
- NEUROLOGIC SIGNS
- RETINAL HEMORRHAGES
- CONVULSIONS
- DELIRIUM
- COMA
Complication

2. HYPERPYREXIA
3. HEMOLYTIC ANEMIA
4. NONCARDIOGENIC PULMONARY EDEMA
5. ACUTE TUBULAR NECROSIS & RENAL
FAILURE  BLACKWATER FEVER DUE TO
>QUININE TREATMENT
Complication

6. ACUTE HEPATOPATHY  MARKED


JAUNDICE, BUT NO LIVER FAILURE
7. HYPOGLYCEMIA
8. ADRENAL INSUFFICIENCY-LIKE SYNDROME
9. CARDIAC DYSRHYTHMIAS
10, GASTROINTESTINAL SYNDROMES
11. LACTIC ACIDOSIS & HYPOGLYCEMIA
12. PNEUMONIA
13. WATER & ELECTROLYTE IMBALANCE
Todays challenges

• Malaria is still a big concern in Indonesia


health problem
• Challenge of resistance in antimalarial drug
• Treatment policy to overcome the problem by
using artemisinine derivatives
• Clinical malaria diagnosis no longer used
• Malarial elimination program in Indonesia
What
MALAR IA
can

• Many cases worldwide


• High mortality of severe malaria
• Resistance to drugs
• Serious effects in pregnancy

we
do?
Treatment of malaria

• Ideally all patients should be treated in hospital


• Indications for hospital admission:
• All children ≤ 1 year (and consider admitting children up to 5
years where possible)
• All pregnant patients
• All patients ≥ 65 years
• Immuno-compromised patients where possible
• Severe malaria or danger signs

GUIDELINES FOR THE TREATMENT OF MALARIA IN SOUTH AFRICA, 2009


Uncomplicated malaria

• Symptomatic malaria without signs of severity or


evidence of vital organ dysfunction.
• Treatment objectives:
• eradicate the infection
• prevent the emergence and spread of drug resistance
• combination of two or more antimalarials with different
mechanisms of action
• Always give a full course of effective treatment

Guidelines for the treatment of malaria, WHO 2010


Uncomplicated malaria

• Treatment coverage:
• Treatment of P.vivax or P.ovale infection
• Treatment of mild/moderate P.falciparum infection,
P. falciparum and P.vivax mixed infection

• Antimalarial drugs:

ACT (1st line) / non-ACT (2nd line) + Primaquine

Guidelines for the treatment of malaria in Indonesia, Ministry of Health RI, 2009
Artemisinin derivatives
• Very short T½  should be given in a longer period 
to avoid relaps

Combination Artemisinin
& other antimalarial T½ > Duration
therapy <

Drug with different mechanism Prevent resistance


of antimalarial drug

Davis TME, Karunajeewa HA, Ilett KF. Artemisinin-based combination therapies for uncomplicated malaria. MJA 2005; 182
(4):181-5.
Yeung S, Pongtavornpinyo W, Hastings IM, Mills AJ, White NJ Am. J. Trop. Med. Hyg. 2004; 71(Suppl 2): 179–86.
McIntosh H,Olliaro P. Artemisinin derivatives for treating uncomplicated malaria. Cochrane Database of Systematic Reviews 1999.
Artemisinin derivatives
SHOULD NOT be used as monotherapies for
the treatment of uncomplicated malaria
as this will promote resistance to this
critically important class of antimalarials
Available ACT in 2010, WHO
(Arthemisinin-based Combination Therapy)

Drugs Composition Form


Artemether + 20 mg + 120 mg Fixed dose tablets
lumefantrine
Artesunate + 25 mg + 67,5 mg
amodiakuin
50 mg + 135 mg Fixed dose tablets
100 mg + 270 mg
50 mg + 150 mg (base) Co-blistered tablets
Artesunate + 200 mg + 250 mg Co-blistered tablets
meflokuin
Dihidroartemisinin 40 mg + 320 mg Fixed dose tablets
+ piperakuin
Artesunate + 50 mg + 500/25 mg Co-blistered tablets
sulfadoksin /
pyrimethamine
World Health Organization. Antimalarial medicines procured by WHO. 2010
WHO recommended ACTs
 Artemether (20 mg) - lumefantrine (120mg)
(Coarthem®) 2 x 4 tablet, in 3 days
 Artesunate (4mg/BW/day) + amodiaquine (10mg/BW/day)
(Artesdiaquine®, Artesuamoon®) once daily in 3days
 Artesunate (4mg/BW/day once daily in 3 days) + Mefloquine (25
mg/BW split over 2 or 3 days)
 Artesunate (4mg/BW/day once daily in 3 days) + Sulfadoxine-
pyrimethamine (25mg/1.25mg base/BW on 1st day)

Guidelines for the treatment of malaria, WHO 2010


Uncomplicated malaria
Treatment of P.vivax or P.ovale infection (1)
FIRST LINE : ACT + PRIMAQUINE

Artesunate (200mg/day, in 3 days) +


amodiaquine (600mg/day, in 3 days)

Artemether 20 mg +
lumefantrine 120 mg; 0.25 mg/BW/day
2x4 tablets for 3 days in 14 days
Dihydroartemisinin 40 mg + piperaquine
320 mg
2 tablets initial dose,
2 tablets in the next 8, 24, and 32 hours

Guidelines for the treatment of malaria Ministry of Health RI, 2009, WHO 2010
Uncomplicated malaria
Treatment of P.vivax or P.ovale infection (2)

SECOND LINE
QUININE SULFA + PRIMAQUINE
3 X 400-600 mg/day 0.25 mg/BW/day
in 7 days in 14 days

Guidelines for the treatment of malaria, Ministry of Health RI, 2009, WHO 2010
Uncomplicated malaria
Treatment of P.vivax or P.ovale infection (3)

CHLOROQUINE SENSITIVE
CHLOROQUINE BASE 150 MG + PRIMAQUINE

1st day : 4 + 2 tablets


2nd & 3rd day : 2 tablets
OR 1 X 15 mg
1st & 2nd day : 4 tablets in 14 days
3rd day : 2 tablets

Guidelines for the treatment of malaria, Ministry of Health RI, 2009, WHO 2010
Uncomplicated malaria
Treatment of mild/moderate P.falciparum infection,
P. falciparum and P.vivax mixed infection (1)

FIRST LINE P falciparum inf.


ACT 0.75 mg/BW
+ single dose
PRIMAQUINE
Mixed infection
Day 1-14: 0.25 mg/BW

Guidelines for the treatment of malaria, Ministry of Health RI, 2009, WHO 2010
Uncomplicated malaria
Treatment of mild/moderate P.falciparum infection,
P. falciparum and P.vivax mixed infection (2)

SECOND LINE
QUININE + DOXY/TETRA + PRIMAQUINE
• Quinine: 3x400-600 mg in 7 days
• Doxycycline: 2 x 2 mg/BW in 7 days
• Tetracycline:4 x 4-5 mg/BW in 7 days
• Primaquine:
• 0.25mg/BW in 14 days vivax /mixed
• 0.75mg/BW single dose P.F inf.
Key tools of prevention

• Be Aware: risk factor, incubation period, symptom

• Avoid being Bitten by mosquitoes

• Chemoprophylaxis

• Immediately seek Diagnosis & treatment: if fever occur 1


week – 3 months after arrival in endemic areas
Malaria Risk Prevention
TIPE I Transmission risk very low Bite avoidance

Risk of malaria vivax or Bite avoidance +


TIPE II falciparum which sensitive to Chemoprophylaxis
chloroquine (chloroquine)

Risk of malaria vivax


TIPE III /falciparum, + probability of Bite avoidance +
chloroquine resistance Chemoprophylaxis
 High risk of malaria (according drug
falciparum + drug resistance sensitivity in the area)
TIPE IV
 Moderate risk of malaria
falciparum + high resistance

WHO. International Travel & Health 2008


Avoid being Bitten by mosquitos

• Insecticide treated net (ITN): (conventional ITN or Long-


lasting insecticidal nets (LLINs)  prevent infectious
mosquito bites.

• Indoor Residual Spraying (IRS): indoor application of long-


lasting chemical insecticides (DDT)

• Other vector (mosquito) controls: larviciding and


environmental management, repellent, clothes, fogging,
domestic insectiside

WHO, The Roll Back Malaria Partnership 2008: Global Malaria Action Plan.
Chemoprophylaxis

Causal
Prophylaxis

SuppressiveP
rophylaxis

Guidelines for Malaria Prevention in Travellers from the United Kingdom. 2007
Chemoprophylaxis

• Recommended drugs:
• Chloroquine
• Proguanil
• Chloroquine + proguanil
• Mefloquine
• Doxicycline
• Atovaquone + proguanil

Guidelines for Malaria Prevention in Travellers from the United Kingdom. 2007
Chemoprophylaxis
Doxicycline

• Recommended by Ministry of Health RI, 2009


• Suppresive prophylaxis (effectivity ~ mefloquine)
• Adult dose: 100mg/day, start on 1st -2nd day before
arrival, until 4 weeks after leaving out the area
• Not recommended for > 3 month of using, children,
and pregnant woman. (Ministry of Health RI, 2009)
• !! Predisposition of Candidosis vagina

Ohrt, C, Richie TL, Widjaja H et al. Annals of Internal Medicine. 1997;126:963-72


Guidelines for the treatment of malaria in Indonesia, Ministry of Health RI, 2009
Chemoprophylaxis
In pregnant traveller

• Save: chloroquine and proguanil (+ folic acid


5mg/day) less protection to resistant strain
• Mefloquine:
• Few reported side effects
• Carefully use for 2nd & 3rd trimester pregnancy in area
with chloroquine resistance
• Doxicycline  CONTRA INDICATED

Guidelines for Malaria Prevention in Travellers from the United Kingdom. 2007
Chemoprophylaxis
In pregnant traveller in endemic area

• Intermittent Preventive Treatment (IPT, WHO


2007): Recommended Sulfadoxine-
pyrimethamine
• Single dose; minimum use is twice, since
trimester II until partus
• Prevalence of HIV in pregnancy > 10%  the 3rd
dose should be given on the last antenatal care

?
• World Health Organization. Malaria in pregnancy: guidelines for measuring key monitoring and evaluation indicators. 2007.
• Gamble C, Ekwaru JP, ter Kuile FO. Insecticide-treated nets for preventing malaria in pregnancy. Cochrane Database Syst Rev 2006;2:
CD003755.
Chemoprophylaxis
For long term

• Chemoprophylaxis is pointed for people who traveling not


in a long period
• Not recommended for long term use (3 months)
• Consider of using personal protection (net, repellent,
etc)

Guidelines for the treatment of malaria in Indonesia, Ministry of Health RI, 2009
Severe malaria
The presence of one or more of these features:
• Clinical manifestation: • Laboratory test:
• Prostration • Severe anaemia
• Impaired consciousness • Hypoglycaemia
• Respiratory distress • Acidosis
• Multiple convulsions • Renal impairment
• Circulatory collapse • Hyperlactataemia
• Pulmonary oedema • Hyperparasitaemia
• Abnormal bleeding
• Haemoglobinuria
• Jaundice

Guidelines for the treatment of malaria, WHO 2010


Severe malaria

• Treatment objectives:
• Prevent death
• Prevention of recrudescence, transmission or emergence of resistance
• Prevention of disabilities
• Principal treatment:
• Supportive therapy
• Antimalarial drug
• Complication management

Guidelines for the treatment of malaria, WHO 2010


Severe malaria
Supportive therapy

• Fluid, acid-base, and electrolyte balance


• Antipyretic
• Anti convulsants:
• Diazepam 10 mg, IV

Guidelines for the treatment of malaria in Indonesia, Ministry of Health RI, 2009
Guidelines for the treatment of malaria, WHO 2010
Severe malaria
Antimalarial drugs (1)

Artemisinin
• Artemether
• Day 1 : 3,2mg/BW/12hours (2 x 1,6mg/BW/12hours;im)
• Day 2 - 4 : 1,6mg/BW/day, im
• Artesunate
• Day 1 : 2,4mg/BW, iv in 1st hour,  2,4mg/BW/iv in hour 12 &
24
• Day 2 - 7 : 2,4mg/BW/hr, iv

After conscious continue with


• Artesunate + amodiaquine OR
• Quinine + Tetracycline / doxycycline / clindamycin
Guidelines for the treatment of malaria, WHO 2010
Severe malaria
Antimalarial drugs (2)

Quinine HCl 25%


• Diluted in 500cc dextrose 5% or NaCl 0.9%, give
during the first 4 hours, then rest in the next 4
hours:
• Loading dose: 20 mg/BW (single dose)
• Maintenance dose: 10 mg/BW, repeat until the
patient able to receive oral medication
• After conscious, continue by oral quinine 10mg/BW
every 8 hours, + tetracycline / doxicycline /
clindamycin until day 7.

Guidelines for the treatment of malaria, WHO 2010


Severe malaria
Complication management

 Hypoglycaemia
 Dextrose 40%, IV bolus 25-50 cc, then dextrose 10%, drip
500 cc every 4-6 hours
 Keep the nutrition intake (NGT)
 Acute kidney failure
 Keep the fluid & electrolyte balance
 Dyalisis (if there is an indication)
 Lung oedema / ARDS
 Fluid & electrolyte balance (max 1500 cc/24 hours)
 Diuretic
 Ventilator

Guidelines for the treatment of malaria, WHO 2010


Severe malaria

Exchange blood transfusion

Indication:
• Parasitaemia> 30% without severe complication
• Parasitaemia> 10%:
• With severe complication
• With treatment failure after 12-24 hours optimal antimalarial
• With bad prognosis (old age, late stage parasites/skizon in blood)
Malaria in pregnancy

• More common
• More atypical
• More severe
• More fatal
• Selective treatment
• Various complication
Malaria in pregnancy

• 2nd and 3rd trimesters of pregnancy are more likely to


develop severe malaria
• Complication: anemia, pulmonary oedema, hypoglycaemia
• Maternal mortality is approximately 50%
• Fetal death & premature labour are common

Guidelines for the treatment of malaria, WHO 2010


Malaria in pregnancy

• Principal treatment:
• Supportive therapy
• Antimalarial drug
• Management of complication
• Management of labour
Malaria in pregnancy
Supportive therapy

• Supplementation of Fe & folic acid


• Blood transfusion in severe anemia (Hb<7g/dl)
• Adequate nutrition

Nosten F, McGready R, Mutabingwa T. Case management of malaria in pregnancy. Lancet


Infect Dis 2007; 7:118-25.
Malaria in pregnancy
Antimalarial drugs (1)

• Uncomplicated malaria falciparum (trimester I)


Quinine 3 x 10 mg/BW/day
1st Episode + + 7 days
Clindamycin 3 x 5 mg/BW/day

 Repeat Quinine
+ Clindamycin
Failure
 ACT
of
 Artesunate 2 mg/BW/day
7 days
treatment
+ +
Clindamycin 3 x 5 mg/BW/day

• World Health organization. Guideline for the treatment of Malaria 2010.


Geneva.
• Case management of malaria in pregnancy. Lancet Infect Dis 2007; 7:118-25.
Malaria in pregnancy
Antimalarial drugs (2)
• Uncomplicated malaria falciparum (trimester II & III)

 ACT Dose
1st Episode
 Artesunate + Clindamycin above

Failure  Other ACT


Dose
of Artesunate + Clindamycin above
7 days
treatment  Quinine + Clindamycin

• World Health organization. Guideline for the treatment of Malaria 2006.


Geneva.
• Case management of malaria in pregnancy. Lancet Infect Dis 2007; 7:118-25.
Malaria in pregnancy
Antimalarial drugs (3)
• Choices of ACT
Artemether (20 mg) +
2 x 4 tablets/ day 3 days
lumefantrine (120 mg)
Artesunate (50 mg) +
Amodiaquine (153 mg) 1 x 4 tablets/ day 3 days

Artesunate (50 mg) + 1 x 4 tablets/ day


Sulfadoxine-pyrimethamine + 3 days
(500/25 mg) 3 tablets only at day I
1 x 4 tablets/ day
3 days
Artesunate (50 mg) + +
+
Mefloquine (250 mg) 1 x 4 tablets/ day in day I,
2 days
1 x 2 tablets/ day in day II
• Case management of malaria in pregnancy. Lancet Infect Dis 2007; 7:118-25.,WHO 2010
Malaria in pregnancy
Antimalarial drugs (4)
• Severe malaria
Until able
2 – 4 mg/BW at hour 0, 12
Early fase Artesunate of oral Parenteral
& 24; then every 24 hours drug

Artesunate+ 2 mg/BW/day
Late fase 7 day oral
Clindamycin 3 x 5 mg/BW/day

Alternative 20 mg/BW (loading dose);


for Quinine then 10 mg/BW every 8 7 day Parenteral
early fase hours

Alternative Quinine + 3 x 10 mg/BW/day


7 day oral
for late fase Clindamycin 3 x 5 mg/BW/day.

• Case management of malaria in pregnancy. Lancet Infect Dis 2007; 7:118-25, WHO 2010.
Malaria in pregnancy
Antimalarial drugs (5)

• Malaria non-falciparum
• Chloroquine (25 mg base /BW); except for P. vivax in south Asia
(around Indonesia) with high resistance, choose quinine.
• Alternative: Amodiaquine  very limited data about effectivity &
safety in pregnancy

• Case management of malaria in pregnancy. Lancet Infect Dis 2007; 7:118-25, WHO 2010.
Prognosis

Uncomplicated & untreated primary attack of


p. Vivax, p. Ovale, or p. Falciparum malaria usually
Lasts 2-4 weeks; p. Malariae about twice as long.
- With prompt antimalarial therapy, the prognosis
Is generally good, but in p. Falciparum infections,
When severe complications develop, the prognosis
Is poor even with treatment