1

Local resistance management and containment response

Dr Wichai Satimai: Director, Bureau of Vector Borne Diseases, Department of Disease Control, Ministry of Public Health, Thailand

15th RBM Partnership Board Meeting

November 10-11, 2008

New Delhi, India

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Goal•To reduce malaria morbidity and mortality

Objectives

•To prevent transmission of drug resistance Malaria

•To develop the network of all partners for malaria control

3

Myanmar

Lao PDR

Cambodia

Malaysia

N

Source: Malaria Cluster, Department of Disease Control, MoPH

Integrated Provinces

Pre- integrated Provinces

Vertical Program

4

0

2

4

6

8

10

12

14

16

18API/1,000

API per 1,000 MMR per 100,000

Annual parasite incidence (per 1,000) and malaria mortality rate (per 100,000)

0.57

0.18

5

6

Fiscal Year

Malaria Cluster, Department of Disease Control, Ministry of Public Health.Fiscal Year :Oct - Sep * Preliminary data

91,703

57,883

67,749

58,846

47,948

33,983

38,902

32,38530,482

27,110

27,381

27,539

30,338

36,31335,587

27,767

25,700

25,368

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

90,000

100,000

2000 2001 2002 2003 2004 2005 2006 2007 2008

THAI Non-Thai

Fisc al Ye ar

Number of c ases

Thai and Non-Thai malaria casesFiscal Year 2000-2008

7

0

100,000

200,000

300,000

400,000

500,000

1965 1968 1971 1974 1977 1980 1983 1986 1989 1992 1995 1998 2001 2004 2007

no of cases

P. falciparum

P.vivax

Fiscal Year

Number of cases

Source: Malaria Cluster, Department of Disease Control, Thai MoPH

CQ ’45-‘73

SP’73-’82

QT’82-’85

MSP’85-’90

M, MSP’90-’95 M,

M+ATS (2 days)’95-’05

’05-07M+ATS2 days;

From ’08 3 days

No. of Malaria Cases by Parasite Species and 1st Line Drug Regimens for P. falciparum, Thailand, 1965-2008

8

Local resistance management

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MYANMAR

THAILAND

LAOSVIETNAM

VIETNAM

MALAYSIAINDONESIA

CAMBODIA

GULF OF THAILAND

ANDAMON

SEA

TUNGIA GULF1.Chiang Mai

2. Mae Hong Son

3. Tak

4. Kanchanaburi

5. Ratchaburi9. Trat

8. Chanthaburi

7. Ubonratchathani

6. Ranong

Activities

• Routine follow-up• In vivo testing• In vitro testing• Drug Quality Assurance

Monitoring Malaria Drug ResistanceMonitoring Malaria Drug Resistance in Thailand in Thailand

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Refs.Study site, Year

DoseSubjects (N)

Follow-up duration Efficacy

Mey Bouth et al, Siem Reap Conf.,2002.  

Pailin Cambodia

2002

AM4,AM3, AM2

3 days

Children and adults

(70)

28 days 87.0%(PCR-

corrected)

Vijaykadga et al, TMIH 2006.

Trat Thailand

2003

ATS (600

mg) + MFQ 1,250 mg) in 2 days

Mostly adults

(>=10 yrs) (44)

28 days 78.6%

Mey Bouth et al, TMIH 2006.

Pailin Cambodia

2004

ATS 12 mg/kg in 3 days + MFQ 25 mg/kg.

Children and adults

(81)

42 days 79.3%(PCR-

corrected)

Increasing Evidence of ATS-MFQ Failures on the Thai-Cambodian Border

1111

Mef 25 mg/kg + Art 12 mg/kg + Pri 30 mg; two days regimen

** PCR corrected

N ACPR% LPF% LCF% ETF%

MHS 2006: 28d 191 94.8 2.09 3.66 0

TAK 2006: 28d 46 89.1 2.17 8.7 0

KB 2005: 28d 29 96.7 0 3.3 0

RB 2006**: 42d 48 97.9 0 2.1 0

RN 2004: 28d 40 90 2.5 5.0 2.5

TR 2006: 28d 29 86.2 13.8 0 0

Treatment Efficacy of Mefloquine and Artesunate against falciparum malaria at seven areas in Thailand, 2004 - 2006

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Prevalence of parasitemia on D2 postRx has significantly increased over the past decade on Thai-Camb border, but not on Thai-Burmese border.

Source: Thai MOPH

Thai NMCP’s ATS-MFQ in vivo monitoring of 1,267 Pf patients 1997-2007.

OR(adj.)* for each year: - Cambodian border 1.40 (95% CI: 1.2, 1.7, p<0.0001)* - Burmese border 0.98 (95% CI: 0.8, 1.2, p=0.83)

*The odds of D2 parasitemia increases, on average, 40% per year on the Cambodian border but not increasing on the Burmese border.

Sensitivity of P. falciparum to Artesunate?

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Tak

Ranong

KanchanaburiRatchabur

i Trat

Artesunate 12mg/kg + Mefloquine 25 mg/kg

Divided dose given

for 2 days

Antimalarial efficacy in the treatment of

falciparum malaria patients in the year 2007

Mae Hong Son

Antimalarial efficacy in the treatment offalciparum malaria in the Year 2007

ARS+MQ (1,250), 2D0

10

20

30

40

50

60

70

80

90

100

93.5

82.891.8

92.9

91.7

RN TK RN RB TR

15

Tak

Ranong

Ratchaburi

Yala

Artesunate 12mg/kg + Mefloquine 25 mg/kg

Divided dose given for 3 days

Efficacy of ARS-MQ in the treatment of falciparum malaria patients in the year 2008

Mae Hong Son

Ubonratchathani

Efficacy of ARS-MQ in the treatment offalciparum malaria in the Year 2008

0

10

20

30

40

50

60

70

80

90

10097.1

100

98.5

100 100

93.5

MH RB TK UB Yala RN

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Constraints and key challengesConstraints and key challenges

• Multi-drug resistant of falciparum malaria.

• High proportion of reported foreign malaria cases, thus scaling up the effective interventions in all endemic villages focusing on both Thai and Non-Thai population is essential.

• Increase of cases in the unrest areas along the southern border provinces, thus scaling up the effective interventions in this area is needed.

• The program is being decentralized resulting in decrease of specialized field staff, thus capacity building of local health personnel on malaria control is needed

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Why multi-drug resistance was constraint to

Malaria Control in Thailand? • A large number of migrant laborers coming from

different malarious areas import different strains/genotypes of P.falciparum and over a period of time mixed population of different strains/genotypes infect individuals.

• High population movement along the border still happened from both side, especially during harvesting and agriculture season.

• Unknown factors influence to multi drug resistance, more further research are needed.

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Containment response

Phase 1: Containment of artemisinin-tolerant Containment of artemisinin-tolerant P. falciparumP. falciparum parasitesparasites in 7 provinces in Thailand in 2009 – 2010. in 7 provinces in Thailand in 2009 – 2010. Request fund from Bill- Milinda Gate FoundationRequest fund from Bill- Milinda Gate Foundation

Phase 2: Containment of artemisinin-tolerant Phase 2: Containment of artemisinin-tolerant P. falciparumP. falciparum parasitesparasites in 7 provinces in Thailandin 7 provinces in Thailand Request fund from GFM R9Request fund from GFM R9

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GoalGoal

Containment of artemisinin-tolerant Containment of artemisinin-tolerant Plasmodium falciparumPlasmodium falciparum parasites parasites

in 7 provinces in Thailand in 7 provinces in Thailand

in 2009 - 2010in 2009 - 2010

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0

1000

2000

3000

4000

5000

6000

7000

8000Trat

Chanthaburi

Sakaeo

Surin

Srisaket

Ubonratchatani

Malaria cases in Thai-Cambodian Border, 1995-2007

No cases

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Containment Implementation

Areas in Zone 1 and Zone 1 and 22

Containment Implementation

Areas in Zone 1 and Zone 1 and 22

Myanmar

Lao PDR

Cambodia

Malaysia

N

1

5432

6 7 1. Trat

2. Chanthaburi

3. Sakaeo

4. Burirum

5. Surin

6. Srisaket

7. Ubonratchathani

2222

ChantaburiChantaburi

Containment Implementation Areas in Zone 1 (2008)

Tambon vill pop

PongNamron 5 45

38,652

Soidao 4 5262,634

Borai 2 1110,871

Total 11 108112,157

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Mass ScreeningPatients

Biometric Reader

Application

Disease Clinic Post

Vectorborne Disease Control Center VBDCOffice of Disease Prevention and Control ODPCVector Borne Disease Control Unit VBDUMinistry of Public Health MOPH

SMS Server

GIS Server

Malaria database Web Server

Server Farm at BioPHICSFac . of Trop . Med ., MAHIDOL Univ .

Remote Areas BIOPHICSMahidol University

Malaria Center

HealthVolunteers equipped with loaded Malaria Application

PDA

GIS MappingSMS Drug

Resistance Alert /FU treatment monitoring

Malaria Reports andWarning System

Internet

Internet

Drug Resistance Action Team

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1. To eliminate artemisinin tolerant parasites by detecting all malaria cases in target areas and ensuring effective treatment and gametocyte clearance using zone specific combination therapies.

• Change the first line treatment for uncomplicated falciparum malaria in Zone 1 to a non artemisinin containing combination

• Improve coverage of passive case detection: MC and MP

• Conduct active case detection: mass screening of migrants and focus investigation.

• Implement directly observed treatment and conduct 28 day follow up of all confirmed falciparum malaria cases.

• Establish management system for treatment failure cases

Objectives and activities

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Objectives and activities

2. To prevent transmission of artemisinin tolerant parasites by mosquito control and personal protection.

Increase coverage of LLINs to 1 per person (residents, migrants and military)

Distribute LLI hammock nets for personal protection for local residents, migrants and military spending nights in the forest

Distribute repellents for personal protection for plantation workers and soldiers patroling at night.

Conduct IRS in foci of transmission detected as a result of case investigation.

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Objectives and activities

3. To support containment/elimination of artemisinin tolerant parasites through comprehensive BCC, community mobilisation and advocacy

Review communication/BCC strategy and develop strategy for containment (harmonized with that of Cambodia) targeting all risk groups.

Implement BCC/IEC, including massive health promotion & community mobilization to ensure high turnout for ITN campaign and to promote appropriate use.

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Objectives and activities

4. To undertake basic and operational research to fill knowledge gaps and ensure that strategies are evidence-based

Characterization of artemisinin tolerant parasites through: clinical trials (including PK studies); development of an in vitro test and molecular markers

Mapping of artemisinin tolerant parasites in 8 sentinel sites using a simplified in vivo test and molecular markers; assessment of effectiveness of Malaria Posts.

Monitoring residual effect of LLIN/LLIHN in sentinel sites; acceptability of all net types; entomological study in areas of changing forest ecology; assess additional protection of using repellents.

Studies to characterize mobile/migrants population movement and behavior; Assessment of feasibility and impact of mass screening and treatment to eliminate artemisinin

Assess the effectiveness of mass screening and treatment of positive cases to detect and treat asymptomatic Pf. infections

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5. Provide effective management system to enable rapid and high quality implementation of the strategy

Establish and maintain comprehensive malaria surveillance and active case investigation system in 13 Provinces bordering with Cambodia and Myanmar.

Hold cross-border coordination meetings.

Establish migrant networks to improve information sharing on malaria in source, transit and destination communities and at work sites

Strengthen human resources at all levels for management and implementation related to containment efforts

Increase supervision capacity to cope with containment associated increase in workload.

Strengthen collection of routine M&E data.

Objectives and activities

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