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MALARIA DIAGNOSIS AND TREATMENT IN BORDER AREAS: WHAT SHOULD WE PAY ATTENTION TO? Asep Purnama TC Hillers Hospital, Maumere, NTT
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Malaria border area

Jul 02, 2015

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Page 1: Malaria border area

MALARIA DIAGNOSIS AND

TREATMENT IN BORDER AREAS: WHAT SHOULD WE PAY ATTENTION TO?

Asep Purnama

TC Hillers Hospital, Maumere, NTT

Page 2: Malaria border area

STRATEGIES

Prevention

Vector control, Long Lasting Insecticide Net, Repellent etc

Accurate diagnosis

Prompt treatment with ACT

Partnership

Increase Coverage of Service

Erna Tresnaningsih, Direktur Pemberantasan Penyakit Bersumber Binatang, Depkes RI

Seminar Nasional Manajemen Malaria Terkini, Manhattan Hotel-Jakarta, 14 Juni 2008

Page 3: Malaria border area

MALARIA DIAGNOSISPROBLEMS

Page 4: Malaria border area

Clinical responses to malaria infection vary widely

Page 5: Malaria border area

CLINICAL MALARIA, BLOOD SAMPLE TAKEN & POSITIVE DIAGNOSIS IN INDONESIA

Not all Malaria cases are diagnosed by microscopist or RDT

Slide positive malaria cases don’t decrease significantly

0

500,000

1,000,000

1,500,000

2,000,000

2,500,000

3,000,000

3,500,000

2000

2001

2002

2003

2004

2005

2006

2007

J an-Mar'08

Page 6: Malaria border area

1475704

1210530

998791

756833

480048

0

200000

400000

600000

800000

1000000

1200000

1400000

1600000

2000 2001 2002 2003 2004

MALARIA KLINIS DAN PEMERIKSAAN SEDIAAN DARAH

MALARIA DI JAWA BALI TAHUN 2000-2004

Klinis Pem SD

0

200000

400000

600000

800000

1000000

1200000

1400000

1600000

1800000

2000000

2000 2001 2002 2003 2004

17025081522831

168617617325571974882

404714 389477 337583 348366479441

MALARIA KLINIS DAN PEMERIKSAAN SEDIAAN DARAH MALARIA DI

LUAR JAWA BALI TAHUN 2000-2004

Klinis Pem SD

Page 7: Malaria border area

0

20000

40000

60000

80000

100000

120000

2000 2001 2002 2003 2004

S EDI AAN DARAH M ALARI A P OS I TI F

DAN M ALARI A P f DAN M I X D I J AWA BALI

TAHUN 2 0 0 0 - 2 0 0 4

SD Posit if Pf + mix

155796181315

140769 148478132095

0

50000

100000

150000

200000

2000 2001 2002 2003 2004

SED IA A N D A R A H M A LA R IA POSIT IF D A N M A LA R IA Pf D A N

M IX D I LU A R JA W A B A LI

TA HU N 2 0 0 0 - 2 0 0 4

SD Posit if Pf + mix

Page 8: Malaria border area

MALARIA DIAGNOSISWhat should we pay attention to?

Prompt and accurate diagnosis is critical to the

effective management of malaria

Based on microscopic diagnosis/RDT

Capacity building

Equipment (microscope, RDT)

Cost

Quality Control

Page 9: Malaria border area

Survey of General Practitioner’s

Knowledge, Attitude and Practice on Malaria

in Sikka District, East Nusa Tenggara 2008

Jane Hidayat, Asep Purnama

Page 10: Malaria border area

MALARIA TREATMENT

PROBLEMS

Page 11: Malaria border area

P. falsiparum : chloroquine resistance

Countries with at least one study indicating chloroquine total failure rate > 20%

No recent data available

Countries with at least one study indicating chloroquine total failure rate > 10%

Page 12: Malaria border area

P. falsiparum:

Sulfadoxin-pyrimethamine resistance

Countries with at least one study indicating sulfadoxine-pyrimethamine total failure rate > 20%

No failure reported

Sulfadoxine-pyrimethamine total failure rate < 10%

No recent data available

Countries with at least one study indicating sulfadoxine-pyrimethamine total failure rate > 10%

Page 13: Malaria border area

P. vivax

prophylactic or treatment failure

P. vivax prophylactic or treatment failure

Page 14: Malaria border area

Anti Malaria Drug Resistance In Indonesia,

1978 - 2003

RESISTANCE OF PLASMODIUM TO

MALARIA DRUGS IN INDONESIA

Page 15: Malaria border area

SAFE & EFFECTIVE DRUGS

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COMPLIANCE

Page 17: Malaria border area

COST

Page 18: Malaria border area

MALARIA TREATMENTWhat should we pay attention to?

Artemisinin based Combination Treatment

Radical treatment is essential

Outcome focus on clinical cure, parasitological

clearance, and blocking transmission

Monitoring therapeutic efficacy of antimalarial drugs

based on clinical and parasitological responses (in-

vivo 28 days)

Page 19: Malaria border area

74 countries have adopted ACTsContinent Countries Drug Line

AFRICA

Burundi, Cameroon, Congo, Côte d'Ivoire, Democratic Republic of Congo, Eq.

Guinea, Gabon, Ghana, Guinea, Liberia, Madagascar, Eritrea, Mali, Mauritania,

Senegal, Sao Tomé & Principe (ST&P), Sierra Leone, Sudan (S),

Tchad, Zanzibar

AS + AQ 1st

Angola, Benin, Botswana, Burkina Faso, Central African Republic, Comoros,

Ethiopia, Gambia, Guinea Bissau, Kenya, Malawi, Mozambique, Namibia, Niger,

Nigeria, Rwanda, Uganda, S. Africa, Tanzania, Togo, Zambia, Zimbabwe

AL 1st

Côte d'Ivoire, Djibouti, Gabon, Sudan (N), ST&P, Zanzibar AL 2nd

Djibouti, Somalia, Sudan (N) AS + SP 1st

ASIA

Cambodia, Malaysia, Myanmar, Thailand AS +

MQ

1st

Bangladesh, Bhutan, Laos, Philippines, Solomon Islands, Sri Lanka, Vanuatu AL 1st

Indonesia AS + AQ 1st

Afghanistan, India, Iran, Pakistan, Saudi Arabia, Tajikistan, Yemen AS + SP 1st

Viet Nam, China DP 1st

Papua New Guinea AS + SP 2nd

Iran, Saudi Arabia, AL 2nd

SOUTH

AMERICA

Ecuador, Peru AS + SP 1st

Bolivia, Colombia, Peru, Venezuela AS +

MQ

1st

Brazil, Colombia, Guyana, Suriname AL 1st

Updated

1 Oct 2007

Page 20: Malaria border area

INDONESIA’S TREATMENT POLICY

Uncomplicated Pf

ATS3+AQ3+PQ

DHP3+PQ

QN7+DX7/Clin7+PQ

Uncomplicated Pv

ATS3+AQ3+PQ14

DHP3+PQ14

QN7+PQ14

Complicated Pf

QN parenteral-oral7+Dx7/Clin7

Artemether im-AQ3+ATS3

Artesunate iv-AQ3+ATS3

Prophylaxis

Doxycycline

Outbreak containment (MFS)

AQ3+ATS3+PQ1

Page 21: Malaria border area

Since 2004 Artesunate-amodiaquine as the first line ACT for P.falciparum malaria (based on the African study Adjuik M et al, Lancet 2002).

Efficacy of Artesunate-amodiaquine varied between study sites 78-96% (Gasem H et al, 2004 ; Tjitra E et al, 2004; and

Sutanto I et al, 2004; Setyoningrum E et al, 2005; Hasugian et al, CID 2006 ).

Utility of Artesunate-amodiaquine reported low (<50%) due to poor compliance and adherent events because of need to take large number of pills (personal

communication)

Page 22: Malaria border area

ASSESMENT OF CHLOROQUINE AND ARTESUNATE-

AMODIAQUINE COMBINATION EFFICACY FOR THE

TREATMENT OF UNCOMPLICATED FALCIPARUM MALARIA

IN BELU DISTRICT, EAST NUSA TENGGARA

Asep Purnama et al, IJIM 2006:38;327-31

Page 23: Malaria border area

RESULTS

Due to an increase in the chloroquine treatment failure rate

to 47,62%, recruitment was terminated prematurely

A total of 95 of the originally recruited 203 patients were

enrolled in the study

Artesunate-amodiaquine showed superior 28-day cure rate

Chloroquine versus artesunate-amodiaquine was 22/42

[52,38%] versus 49/53 [92,45%]; p<0,01

However , efficacy of As+Aq was <95%, below than WHO

standard

Page 24: Malaria border area

ARTESUNATE - AMODIAQUINE VERSUS CHLOROQUINE

FOR THE TREATMENT OF VIVAX MALARIA

IN MAUMERE, EAST NUSA TENGGARA

National Institute of Health Research and

Development, MOH, Jakarta

Page 25: Malaria border area

RESULTS

A prospective comparative clinical trial of efficacy, safety

and tolerability of As+Aq versus chloroquine for treatment

of uncomplicated vivax malaria with a 28-day follow up

Of a total 105 enrolled patients there were 100 patients

could be analysed

The efficacies of As+Aq and Chloroquine were 88% and

40,8% on day 28 by ITT and 93,2% and 47,2% by

PP, respectively

However , efficacy of As+Aq was <95%, below than WHO

standard

Page 26: Malaria border area

NEED ALTERNATIVE ACTs

ATS3+AQ3

Efficacy <95% (Papua 70-87%)

AR: nausea and vomiting

Compliance? (no of pills)

Cost and accessibility?

QN7+Dx7/Clind

Efficacy ?

AR: dizziness, tinnitus

Poor compliance

Page 27: Malaria border area

IMPROVING ACT

COMPLIANCE

Tolerate: tasteless

Safe: risk groups (infancy

and pregnancy)

adverse events

Simple: fixed-dose regimen

all age groups

single daily dose/

single dose only

CURE RATE

Effective: rapid

broad spectrum

Practice : all species

single dose only

Page 28: Malaria border area

CLINICAL TRIALS ON ACTs

ATS3+AQ3 VS

(ART+PPQ)2

(ATS+PD)3

(ATM+LMF)3 VS

(DHA+PP)Q3

ATS3+AQ3 VS

(DHA+PPQ)3

(ART+NTQ)1 VS

(DHA+PPQ)3

(ART+NTQ)1 VS

(DHA+PPQ)3

(ATS+PD)3 vs

((ATM+LMF)3

(ATS+PD)3 vs

((ATM+LMF)3

(ATS+PD)3 vs

((CQ)3

CQ3 vs (CQ3+SP1) vs AQ3

IV ART vs QN

Parentral ATM vs QN

Page 29: Malaria border area

EFFICACY COMBO VS FIXED REGIMEN

0

0.5

1

1.5

2

2.5

3

3.5

4

Day 0 Day 1 Day 2 Day 3 Day 7 Day 14 Day 21 Day 28

ATS3+AQ3 ART2+PPQ2

0

1

2

3

4

5

6

7

Day 0 Day 1 Day 2 Day 3 Day 7 Day 14 Day 21 Day 28

ATS3+AQ3 ART2+PPQ2

N=352

Artesunate+amodiaquine (ATS3+AQ3) vs Artemisinin+piperaquine (ART+PPQ)2

Pf: 93.8% vs 96.5% Pv:96.5% vs 100% (Tjitra E et al, 2005)

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Artemisinin/naphtoquine P. vivax, P. falciparum, P.mix phase III trial

A Phase III randomized, open label, non-inferiority trial

of artemisinin plus naphtoquine (ARCO) versus dihydroartemisinin

plus piperaquine in adult uncomplicated malaria patients: A Multi-

centre study in Indonesia

Page 39: Malaria border area

Artemisinin/naphtoquine phase III trial Study outline

401 patients randomized

Study duration: April 2007 – August 2008

Treatment : single dose, F/U to 42 days

: Multicentre: 2 sites, 4 hospital

Page 40: Malaria border area

Artemisinin/naphtoquine phase III trialConclusions

The trial demonstrated non inferiority treatment study

Arco vs Duocotecxin

P. vivax 98,7% vs 97,3%

P. falciparum 98,7% vs 97,1%

Both new fixed-dose ACTs are confirmed very

effective, safe and tolerate for treatment of any malaria in

adults, and meet with the recent WHO recommendation for

replacing ineffective drugs

Page 41: Malaria border area

ARTEMISININ FOR SEVERE MALARIA

ARTEMETHER

FCT= 35.5 hours

PCT= 38.9 hours

Regain consciousness= 32 hours

CFR cerebral mal = 37.5%

Overall CFR= 13%

QUININE DIHYDROCHLORIDE

FCT= 37.4 hours

PCT= 41.8 hours

Regain consciousness = 62.8 hours

CFR cerebral mal = 71.4%

Overall CFR= 23%

Tjitra E et al, MJI, 1996

Page 42: Malaria border area

SEAQUAMAT TRIAL

Study design: Open label, multi centre,

randomised, comparison of artesunate

and quinine in severe falciparum

malaria

Study sites: 2003-2005

Bangladesh

Indonesia (Timika Hospital, Timika)

India

Myanmar Target sample size: 2,000 patients 1400 enrolled as at February 2005

Coordination: Wellcome Unit, Bangkok

Page 43: Malaria border area

RESULTS (SEAQUAMAT Group, Lancet, 2005)

Trial stopped early (n=1461) by Safety Monitoring committee because clear benefit with artesunate

Overall reduction in mortality with artesunate 34.7% (95%CI 19-48%) p=0.0002

mortality quinine: 164/731 (22%)

mortality artesunate: 107/730 (15%)

Indonesian national policy change before the results published

Australian policy change 2006

Page 44: Malaria border area

THE IMPORTANCE OF COOPERATION BETWEEN

NEIGHBOURING COUNTRIES

Many health problems are cross border

(malaria, rabies, filaria, DHF etc)

Limited resource: mutual cooperation important

Potential for inefficiency if countries work alone

Sharing expertise and facilities

Cooperation on research projects

Share results of individual research

Cooperation to develop guidelines or policy

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MASS BLOOD SURVEY-YASPEM

Target 45.454 [3 kecamatan]

Blood sample taken 37.974 83,48 %

Results F 351 0,9 %

V 517 1,4 %

Mix 71 0,2 %

Total 939 2,5 %

Page 53: Malaria border area

DROP OUT

Adverse event 18 [1,9%]

Hospitalized 6 [0,6%]

Loss of follow up 8 [0,8%]

Reject to take medicine 12 [1,3%]

Page 54: Malaria border area

SOME EXAMPLES OF POOR PRACTICE

• Giving SP to patients with fever even though blood smear negative

• Treating uncomplicated malaria with parenteral quinine or arthemeter im

• Treating complicated malaria with chloroquine or ACT

• Giving SP for P vivax malaria

• Giving Primaquine 15 mg for 14 days for P falciparummalaria

• Giving all available forms of treatment to the one patient

Page 55: Malaria border area

SOME EXAMPLES OF POOR PRACTICE (contd)

• Using RDT to evaluate response to treatment

• Giving transfusion to malaria patients with mild anaemia

• Using steroids to treat cerebral malaria

• Inadequate fluid for complicated malaria

• Postponing haemodialysis for complicated malaria with acute renal failure

• Unawareness of hypoglycemia in complicated malaria

• Not giving ACT for 3 days

• Giving inadequate doses of artesunate or arthemeter