MALARIA: RECENT MANAGEMENT KURNIA FITRI JAMIL Divisi Penyakit Tropik & Infeksi Bagian/SMF. Ilmu Penyakit Dalam FK-UNSYIAH/RSUZA BANDA ACEH - 2011
MALARIA:RECENT MANAGEMENT
KURNIA FITRI JAMILDivisi Penyakit Tropik & Infeksi
Bagian/SMF. Ilmu Penyakit Dalam FK-UNSYIAH/RSUZA
BANDA ACEH - 2011
OutlineCase illustration
Severe malaria
Facts sheet Uncomplicated malaria
Malaria in pregnancy Prevention
Cases (per 1,000) by country, 2009
WHO. World Malaria Report 2010
Estimated 300-500 million clinical cases each year
Estimated 300-500 million clinical cases each year
Mortality (per 1,000) by country, 2009
Approximately 2.5 million die each year
Approximately 2.5 million die each year
WHO. World Malaria Report 2010
WHO. 2010
P. falciparum Resistance, 2009
Countries at risk of transmission, 2009
WHO. 2010
Insidence (per 1,000) Indonesia 2008ACEH 2,03
SUM-UT 8,15SUM-BAR 2,58RIAU 3,06JAMBI 18,08
SUM-SEL 5,46
BENGKULU 22,96LAMPUNG 2,79
BANGKA BELITUNG 40,58
RIAU 13,32DKI JAKARTA 0JAWA BARAT 0,58JAWA TENGAH 0,07D I YOGYAKARTA 0,03JAWA TIMUR 0,71BANTEN 0,03B A L I 0,17NTB 21,85
NTT 0
KAL-BAR 3,23
KAL-TENG 11,21
KAL-SEL 4,20
KAL-TIM 8,59
SUL-UTARA 16,48
SUL- TENGAH 17,81
SUL- SELATAN 1,51
SUL- TENGGARA 10,26
GORONTALO 13,94
SUL- BARAT 11,98
M A L U K U 39,65
MALUKU UTARA 51,42
IRIAN JAYA BARAT 84,74
PAPUA 167,47
Incidence rate tends to decrease, since Gebrak Malaria or Roll Back Malaria (RBM) initiative in 2000.
In 2008:
AMI decreased to 17.77
API remains in 0.16
In 2008:
AMI decreased to 17.77
API remains in 0.16
Indonesia, Malaria cases
Ministry of Health RI, 2008
API: Annual Parasite InsidenceAMI: Annual Malaria Insidence
Indonesia, Malaria Case Fatality Rate
National target by 2010: number of malaria sufferer would be 5 per 1000 population
Ministry of Health RI, 2008
New Species Case Human Malaria is caused by one of 4 protozoan parasites:
Plasmodium falciparum
Plasmodium vivax
Plasmodium ovale
Plasmodium malariae
Plasmodium knowlesi ?( sighh et al, 2008)
http://www.tulane.edu/-wiser/malaria/cmb.html
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
M A L A R I A
Many cases worldwide High mortality of severe malaria Resistance to drugs Serious effects in pregnancy
What can
we do?
T R E A T M E N T
AND
P R E V E N T I O N
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
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:
Uncomplicated malaria
Guidelines for the treatment of malaria in Indonesia, Ministry of Health RI, 2009
ACT (1st line) / non-ACT (2nd line) + Primaquine
Artemisinin derivatives Very short T½ should be given in a longer period to
avoid relaps
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.
Combination Artemisinin& other antimalarial
Drug with different mechanism
Duration therapy <
T½ >
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
Drugs Composition Form
Artemether + lumefantrine
20 mg + 120 mg Fixed dose tablets
Artesunate + amodiakuin
25 mg + 67,5 mg
Fixed dose tablets50 mg + 135 mg
100 mg + 270 mg
50 mg + 150 mg (base) Co-blistered tablets
Artesunate + meflokuin
200 mg + 250 mg Co-blistered tablets
Dihidroartemisinin + piperakuin
40 mg + 320 mg Fixed dose tablets
Artesunate + sulfadoksin / pyrimethamine
50 mg + 500/25 mg Co-blistered tablets
World Health Organization. Antimalarial medicines procured by WHO. 2010
Available ACT in 2010, WHO (Arthemisinin-based Combination Therapy)
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
Guidelines for the treatment of malaria Ministry of Health RI, 2009, WHO 2010
Uncomplicated malaria
FIRST LINE : ACT + PRIMAQUINE
Treatment of P.vivax or P.ovale infection (1)
Artesunate (200mg/day, in 3 days) + amodiaquine (600mg/day, in 3 days)
Artemether 20 mg + lumefantrine 120 mg; 2x4 tablets for 3 days
Dihydroartemisinin 40 mg + piperaquine 320 mg2 tablets initial dose, 2 tablets in the next 8, 24, and 32 hours
0.25 mg/BW/day in 14 days
SECOND LINE
QUININE SULFA + PRIMAQUINE
Uncomplicated malaria Treatment of P.vivax or P.ovale infection (2)
3 X 400-600 mg/day in 7 days
0.25 mg/BW/day 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)
1st day : 4 + 2 tablets2nd & 3rd day : 2 tablets
OR1st & 2nd day : 4 tablets3rd day : 2 tablets
CHLOROQUINE SENSITIVE
CHLOROQUINE BASE 150 MG + PRIMAQUINE
1 X 15 mg in 14 days
Guidelines for the treatment of malaria, Ministry of Health RI, 2009, WHO 2010
FIRST LINEACT +
PRIMAQUINE
Uncomplicated malaria Treatment of mild/moderate P.falciparum infection, P. falciparum and P.vivax mixed infection (1)
P falciparum inf.0.75 mg/BW single dose
Mixed infectionDay 1-14: 0.25 mg/BW
Guidelines for the treatment of malaria, Ministry of Health RI, 2009, WHO 2010
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.
Uncomplicated malaria Treatment of mild/moderate P.falciparum infection, P. falciparum and P.vivax mixed infection (2)
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
Key tools of prevention
Malaria Risk PreventionTIPE I Transmission risk very low Bite avoidance
TIPE IIRisk of malaria vivax or falciparum which sensitive to chloroquine
Bite avoidance + Chemoprophylaxis (chloroquine)
TIPE IIIRisk of malaria vivax /falciparum, + probability of chloroquine resistance
Bite avoidance + Chemoprophylaxis (according drug sensitivity in the area)
TIPE IV
High risk of malaria falciparum + drug resistance
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.
Causal Prophylaxis
SuppressiveProphylaxis
Guidelines for Malaria Prevention in Travellers from the United Kingdom. 2007
Chemoprophylaxis
Recommended drugs: Chloroquine Proguanil Chloroquine + proguanil Mefloquine Doxicycline Atovaquone + proguanil
Chemoprophylaxis
Guidelines for Malaria Prevention in Travellers from the United Kingdom. 2007
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
ChemoprophylaxisDoxicycline
Ohrt, C, Richie TL, Widjaja H et al. Annals of Internal Medicine. 1997;126:963-72Guidelines for the treatment of malaria in Indonesia, Ministry of Health RI, 2009
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
ChemoprophylaxisIn pregnant traveller
Guidelines for Malaria Prevention in Travellers from the United Kingdom. 2007
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
?
ChemoprophylaxisIn pregnant traveller in endemic area
• 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 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)
ChemoprophylaxisFor long term
Guidelines for the treatment of malaria in Indonesia, Ministry of Health RI, 2009
Severe malaria
Clinical manifestation: Prostration Impaired consciousness Respiratory distress Multiple convulsions Circulatory collapse Pulmonary oedema Abnormal bleeding Haemoglobinuria Jaundice
Laboratory test: Severe anaemia Hypoglycaemia Acidosis Renal impairment Hyperlactataemia Hyperparasitaemia
The presence of one or more of these features:
Guidelines for the treatment of malaria, WHO 2010
Treatment objectives: Prevent death Prevention of recrudescence, transmission or
emergence of resistance Prevention of disabilities
Principal treatment: Supportive therapy Antimalarial drug Complication management
Severe malaria
Guidelines for the treatment of malaria, WHO 2010
Fluid, acid-base, and electrolyte balance Antipyretic Anti convulsants:
Diazepam 10 mg, IV
Severe malariaSupportive therapy
Guidelines for the treatment of malaria, WHO 2010 Guidelines for the treatment of malaria in Indonesia, Ministry of Health RI, 2009
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
Severe malariaAntimalarial drugs (1)
Guidelines for the treatment of malaria, WHO 2010
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.
Severe malariaAntimalarial drugs (2)
Guidelines for the treatment of malaria, WHO 2010
Severe malariaComplication 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
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)
Severe malariaExchange blood transfusion
More common More atypical More severe More fatal Selective treatment Various complication
Malaria in pregnancy
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
Principal treatment: Supportive therapy Antimalarial drug Management of complication Management of labour
Malaria in pregnancy
Supplementation of Fe & folic acid Blood transfusion in severe anemia (Hb<7g/dl) Adequate nutrition
Malaria in pregnancySupportive therapy
Nosten F, McGready R, Mutabingwa T. Case management of malaria in pregnancy. Lancet Infect Dis 2007; 7:118-25.
Uncomplicated malaria falciparum (trimester I)
Malaria in pregnancyAntimalarial drugs (1)
1st EpisodeQuinine
+Clindamycin
3 x 10 mg/BW/day+
3 x 5 mg/BW/day7 days
Failure of
treatment
Repeat Quinine + Clindamycin
ACT Artesunate +
Clindamycin
2 mg/BW/day+
3 x 5 mg/BW/day
7 days
• World Health organization. Guideline for the treatment of Malaria 2010. Geneva.• Case management of malaria in pregnancy. Lancet Infect Dis 2007; 7:118-25.
Uncomplicated malaria falciparum (trimester II & III)
1st Episode ACT Artesunate + Clindamycin
Dose above
Failure of
treatment
Other ACTArtesunate + Clindamycin Quinine + Clindamycin
Dose above 7 days
• 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 pregnancyAntimalarial drugs (2)
Choices of ACTArtemether (20 mg) +lumefantrine (120 mg) 2 x 4 tablets/ day 3 days
Artesunate (50 mg) +Amodiaquine (153 mg) 1 x 4 tablets/ day 3 days
Artesunate (50 mg) +Sulfadoxine-pyrimethamine
(500/25 mg)
1 x 4 tablets/ day+
3 tablets only at day I3 days
Artesunate (50 mg) +Mefloquine (250 mg)
1 x 4 tablets/ day+
1 x 4 tablets/ day in day I,1 x 2 tablets/ day in day II
3 days+
2 days
Malaria in pregnancyAntimalarial drugs (3)
• Case management of malaria in pregnancy. Lancet Infect Dis 2007; 7:118-25.,WHO 2010
Severe malaria
Early fase Artesunate 2 – 4 mg/BW at hour 0, 12 & 24; then every 24 hours
Until able of oral drug
Parenteral
Late fase Artesunate+Clindamycin
2 mg/BW/day3 x 5 mg/BW/day 7 day oral
Alternative for
early faseQuinine
20 mg/BW (loading dose); then 10 mg/BW every 8
hours7 day Parenteral
Alternative for late fase
Quinine + Clindamycin
3 x 10 mg/BW/day3 x 5 mg/BW/day.
7 day oral
Malaria in pregnancyAntimalarial drugs (4)
• Case management of malaria in pregnancy. Lancet Infect Dis 2007; 7:118-25, WHO 2010.
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
Malaria in pregnancyAntimalarial drugs (5)
• Case management of malaria in pregnancy. Lancet Infect Dis 2007; 7:118-25, WHO 2010.
Outcomes
WHO standard protocol classification: Early treatment failure Late treatment failure
Late clinical failure Late parasitological failure
Adequate clinical and parasitological response.
Early treatment failure Day 1-3 occurrence of severe clinical sign Day-2 parasite count > day o Day-3 parasite count >25% day o Day-3 (+) finding of asexual parasite & also fever
Late treatment failure Late clinical and parasitological failure:
▪ Day 4-28: occurrence of severe clinical sign▪ Asexual parasite still existing & also fever
Late parasitological failure:Occurrence of asexual parasite on day 7, 14, 21, and 28 without fever.
Outcomes
Guidelines for the treatment of malaria, WHO 2010
Conclusions Reported number of malaria cases & deaths remains high
Recommended use of ACT + Primaquine for uncomplicated malaria
Recommended use of parenteral artemisinin derivative or quinine for severe malaria
Recommended use of quinine + clindamycin (1st trimester) OR
ACT (2nd & 3rd trimester or failure to quinine in 1st trimester), for malaria in pregnancy
Prevention by mosquito control, avoidance of mosquitos bite and chemoprophylaxis
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