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 15 th RBM Partnership Board Meeting November 10-11, 2008 New Delhi, India

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

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6 Fiscal Year Malaria Cluster, Department of Disease Control, Ministry of Public Health. Fiscal Year :Oct - Sep * Preliminary data Thai and Non-Thai malaria cases Fiscal Year

7 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 ’05-07 M+ATS 2 days; From ’08 3 days No. of Malaria Cases by Parasite Species and 1 st Line Drug Regimens for P. falciparum, Thailand,

8 Local resistance management

9 MYANMAR THAILAND LAOS VIETNAM MALAYSIA INDONESIA CAMBODIA GULF OF THAILAND ANDAMON SEA TUNGIA GULF 1.Chiang Mai 2. Mae Hong Son 3. Tak 4. Kanchanaburi 5. Ratchaburi 9. Trat 8. Chanthaburi 7. Ubonratchathani 6. Ranong Activities Routine follow- up In vivo testing In vitro testing Drug Quality Assurance Monitoring Malaria Drug Resistance in Thailand

10 Refs. Study site, YearDose Subjects (N) Follow-up durationEfficacy Mey Bouth et al, Siem Reap Conf., Pailin Cambodia 2002 AM4, AM3, AM2 3 days Children and adults (70) 28 days87.0% (PCR- corrected) Vijaykadga et al, TMIH Trat Thailand 2003 ATS (600 mg) + MFQ 1,250 mg) in 2 days Mostly adults (>=10 yrs) (44) 28 days78.6% Mey Bouth et al, TMIH Pailin Cambodia 2004 ATS 12 mg/kg in 3 days + MFQ 25 mg/kg. Children and adults (81) 42 days79.3% (PCR- corrected) Increasing Evidence of ATS-MFQ Failures on the Thai-Cambodian Border

11 Mef 25 mg/kg + Art 12 mg/kg + Pri 30 mg; two days regimen ** PCR corrected N ACPR% LPF% LCF% ETF% MHS 2006: 28d TAK 2006: 28d KB 2005: 28d RB 2006**: 42d RN 2004: 28d TR 2006: 28d Treatment Efficacy of Mefloquine and Artesunate against falciparum malaria at seven areas in Thailand,

12 D2 parasitemia is strongly associated with ATS-MFQ Rx failure (28-day FU): OR adj. = 4.15 (95%CI: , p 1,200). in vivo monitoring of ATS-MFQ therapeutic efficacy conducted by the Thai NMCP, Source: in vivo monitoring of ATS-MFQ therapeutic efficacy conducted by the Thai NMCP, (S Vijaykadga & AP Alker, ASTMH 2008 presentation). [ Since MFQ is more slow-acting, ATS is the major determinant of parasite clearance on D2/D3 in ATS-MFQ Rx, given D0 = day of Rx initiation. Presence of D2/D3 parasitemia indicates Delayed Parasite Clearance.] Sensitivity of P. falciparum to Artesunate?

13 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 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?

14 Tak Ran ong Kanchana buri Ratchabur 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

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16 Constraints 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

17 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.

18 Containment response Containment of artemisinin-tolerant P. falciparum parasites in 7 provinces in Thailand in 2009 – Phase 1: Containment of artemisinin-tolerant P. falciparum parasites in 7 provinces in Thailand in 2009 – Request fund from Bill- Milinda Gate Foundation Request fund from Bill- Milinda Gate Foundation Phase 2: Containment of artemisinin-tolerant P. falciparum parasites in 7 provinces in Thailand Request fund from GFM R9

19 Goal Containment of artemisinin-tolerant Plasmodium falciparum parasites in 7 provinces in Thailand in

20 Malaria cases in Thai-Cambodian Border, No cases

21 Zone 1 and 2 Containment Implementation Areas in Zone 1 and 2 Myanmar Lao PDR Cambodia Malaysia N Trat 2.Chanthaburi 3.Sakaeo 4.Burirum 5.Surin 6.Srisaket 7.Ubonratchathani

22 Chantaburi Containment Implementation Areas in Zone 1 (2008) Tamb onvillpop PongNamr on , 652 Soidao , 634 Borai , 871 Total , 157

23 Mass Screening Patients Vectorborne Disease Control Center VBDC Office of Disease Prevention and Control ODPC Vector Borne Disease Control Unit VBDU Ministry of Public Health MOPH Remote Areas BIOPHICS Mahidol University Malaria Center Health Volunteers equipped with loaded Malaria Application PDA GIS Mapping SMS Drug Resistance Alert / FU treatment monitoring Malaria Reports and Warning System Internet Drug Resistance Action Team

24 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

25 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.

26 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.

27 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

28 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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