Malaria di sabang 2011 (terapi malaria)

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:


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 Ministry of Health RI, 2009, WHO 2010


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


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


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


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


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:


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


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)


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)


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


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


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


Principal treatment: Supportive therapy Antimalarial drug Management of complication Management of labour


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.


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


• 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


• 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


• 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

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

Thank YouThank You

Malaria di sabang 2011 (terapi malaria)

Health & Medicine

Transcript of Malaria di sabang 2011 (terapi malaria)