1. Bureau of Vector Borne Disease Control, Thailand. TES result in 2004-2015

2. 1. to report the evaluation of the current first-line treatment for uncomplicated P. falciparum, in Thailand( during 2004-2014) consisting: - artesunate-mefloquine, - Artemether-Lumefantrine [AL) 2. to report the evaluation of the current first-line treatment; chloroquine, for uncomplicated P. vivax, in Thailand. 3. To inform the extent of the resistance spread and to guide malaria treatment guidelines in Thailand. Objectives of presentation

3. Malaria morbidity rate per 1000 population during 2000-2015 Rate Fiscal year Eliminating Option Morbidity rate< 1/ 1000 population

4. Malaria elimination phase in Thailand 2017-2024 Informative source: BVBD 11 Feb 15 2 Ubonratchathani (4,411) 1 Tak (9,777) 3.Yala (1,795) 4.Kanchanaburi (1,281) 5.Mae Hong Son (1,217) 6.Srisaket (1,056) 24,850 cases Year 2015

5. Confirmed Malaria Cases and Deaths (FY 2000-2015) No. of Cases Fiscal year Thai death 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15

6. Percentage Fiscal Year Proportion of Malaria Parasites Species, 1965-2011 38.18 60.78 Source: BVBD

7. First-line treatment for falciparum malaria, National Malaria Control Program, Thailand, 1945-present 2 day regimen3 day regimen

8. 8 ATS-MQ TES sentinel sites, s in Thailand 2004-present Informative source: BVBD 11 Feb 15 AS/MQ

9. Parameters to determined Adequate Clinical and Parasitological Response (ACPR) Early Treatment Failure (ETF), 9

10. Summary of ACPR of ATS-MQ during 2004-2014

11. Summary of EFT ( D3 Pos) of ATS-MQ during 2004-2014

12. Efficacy of 2-day ARS-MQ in the treatment of falciparum malaria 20062004 90% and above 80-89% 50-79% 49% and lower Source: therapeutic efficacy monitoring 2007

13. Efficacy of 3-day ARS-MQ in the treatment of falciparum malaria 90% and above 80-89% 50-79% 49% and lower 2009 Trat, Ubonratchathani data from containment project 28 day FU 20082009 Source: therapeutic efficacy monitoring

14. Efficacy of 3-day ARS-MQ in the treatment of falciparum malaria 90% and above 80-89% 50-79% 49% and lower 20102011-12 Source: therapeutic efficacy monitoring

15. MH ACPR 100% (3) D3 Pos. 0% (0) TK ACPR 80% (10) D3 Pos. 10% (1) RB ACPR 100% (10) D3 Pos. 10% (1) ACPR and D3 positive 3-days ARS (12mg/kg)+MQ (25 mg/kg) Falciparum malaria 2013-2014 (preliminary results) 90% and above 80-89% 50-79% 49% and lower ACPR %

16. ACPR and D3 positive Chloroquine (CQ) Vivax malaria 2013-2014 (preliminary results) 90% and above 80-89% 50-79% 49% and lower ACPR % CB ACPR 100% (3) D3 Pos. 0% (0) RN ACPR 97.14% (35) D3 Pos. 5.71% (2) TK ACPR 100% (44) D3 Pos. 2.27% (1)

17. Efficacy of AL in the treatment of falciparum malaria 90% and above 80-89% 50-79% 49% and lower 2011-12 Source: therapeutic efficacy monitoring

18. P. falciparumTakRanongRatchaburiYalaTotal Enrolled 37522751167 Lost follow up or excluded 480214 Analyzed 33442749153 Treatment outcome: ETF00000 LCF09.1% (4)000 LPF9.1% (3)03.7% (1)2% (1)5.9% (9) ACPR90.9% (31)90.9% (40)96.3% (26)98% (48)94.1% (144) % slide positive on day D160.6% (20)52.3% (23)59.3% (16)2% (1)39.2% (60) D221.2% (7)15.9% (7)22.2% (6)2% (1)13.7% (21) D39.1% (3)4.5% (2)3.7% (1)2% (1)4.6% (7) Therapeutic efficacy of 3-day ARS-MQ in Tak, Ranong, Ratchaburi, and Yala, 2010

19. P. falciparumMHKNUBSUTotal Enrolled 15548279 Lost follow up or excluded 7110018 Analyzed 8438261 Treatment outcome: ETF00000 LCF018.6%(8)0013.11%(8) LPF06.98%(3)12.5% (1)06.56%(4) ACPR100%(8)72.42%(32)87.5%(7)100% (2)80.33% (49) % slide positive on day D175%(6)97.67%(42)100%(8)100% (2)95.08%(58) D212.5%(1)83.72%(36)37.50%(2)065.57%(40) D3055.81%(24)12.5%(1)040.98%(25) Therapeutic efficacy of 3-day ARS-MQ in Mae Hong Son (MH), Kanchanaburi (KN), Ubonratchathani (UB) and Surin (SU), 2011-12

20. P. falciparumRNTKTotal Enrolled 553792 Lost follow up or excluded 11617 Analyzed 443175 Treatment outcome: ETF2.27%(1)01.33%(1) LCF2.27%(1)6.45%(2)4.00%(3) LPF4.55%(2)02.67%(2) ACPR90.91%(40)93.55%(29)92.00%(69) % slide positive on day D186.36%(38)87.10%(27)86.67%(65) D247.73%(21)41.94%(13)45.33%(34) D313.64%(6)6.45%(2)10.67%(8) Therapeutic efficacy of Artemether-Lumefantrine [AL] in Ranong (RN) and Tak (TK), 2011-12

21. Therapeutic Efficacy Studies (TES) in Thailand supported USAID and eleven sentinel sites P. falciparum – AS/MQ : Sisaket, Prachuap Khiri Khan, Chumporn, *Surat Thani, Songkhla and *Yala – DHA/PPQ : Kanchanaburi (till Dec 2015), Ranong, Ubon Ratchathani – PYR/AS : Tak – AL: Tak and Ranong P. vivax – Chloroquine : Chantaburi, Tak, Ranong(TES ended July 2015), Kanchanaburi, and Sisaket * Supported by Regional Artemisinin Containment Initiative Project ( RAI)

22. TES sentinel sites in Thailand 2014-2016 Informative source: BVBD 11 Feb 15 AS/MQ DHA/piq PYR/AS CHL

25. Antimalaria drug resistance in Thailand Plasmodium falciparum 1: ปี 2008 2: ปี 2009 3: ปี 2010 4: ปี 2011- 12 % ACPR

26. Antimalaria drug resistance in Thailand Plasmodium vivax 1: ปี 2009- 2010 2: ปี 2011- 2012 % ACPR

27. The Current Policy on Diagnosis and Treatment(1) Prompt and universal access to efficacious diagnosis and treatment services Provide diagnosis to all suspected cases free of charge Provide treatment to all test-confirmed cases RDT and microscopy are use as the confirmatory test Ensure laboratory quality assurance for confirmatory test G6PD testing performed where available Provide appropriate weight-adjusted ACT DOT 3 d for P.f DOT 14 d for P.v 27

28. ClassificationP.fP.vHealth Facilities UncomplicatedDHA+PIP 3 d Primaquine 1 d Chloroquine 3 d Primaquine 14 d MP, BMP, Health Center, MC Uncomplicated with high risks DHA+PIP 3 d Primaquine 1 d Chloroquine 3 d Primaquine 14 d District Hospital SevereIV Artesunate followed by DHA+PIP IV Artesunate followed by Chloroquine Primaquine District Hospital with facilities Children < 1 yrDHA+PIP 3 dChloroquine 14 dDistrict Hospital Pregnant womenDHA+PIP or QN+Clindamycin Chloroquine 14 dDistrict Hospital 28 The Current Policy on Diagnosis and Treatment(2)

29. 2 nd Line Regimens for Treatment Failures P.f o A. Artemether/Lumifantrine o B. Artesunate + ( Clindamycin or Doxycycline) o C. Atovaquone/Proquanil P.v o DHA+PIP 29

30. Approved Anti-malarial drugs Chloroquine 150 mg tab(27 local manufacturers including GPO, 1 importer) Primaquine 5,15 mg tab ( GPO ) Quinine sulphate 300 mg tab (17 local manufacturers including GPO) Quinine dihydrochloride 600 mg amp. Mefloquine 250 mg tab (4 importers) Artesunate 50 mg tab, 60 mg vial. (1 importer) Atovaquone-Proguanil 250/100 mg tab(2 importers including GSK) Artemether/Lumefantrine 20/120 mg tab( 1 importer : Novatis ) DHA-PIP 40/320, 20/160 mg tab ( 1 importer: Macrophar ) 30

31. Antimalarial Drugs Adverse Reactions,as of Nov 2014 YearArtesunateNon- Artesunate Total 2012114354 2013124961 201452328 Source : Thai FDA

32. Investigations and Treatment Outcomes 2013 FY Number of indigenous cases 21,799 Cases % of Pf confirmed malaria cases investigated o (8911)* 100.00 / (10496) = 84.90 % % P.f confirmed cases received ACT o (8643) * 100.00 / (10496) = 82.35 % % DOT of ACT o (3418) * 100.00 / (8643) = 39.55 % 32

33. Investigations and Treatment Outcomes 2013 FY % Day3 slide positive after ACT by DOT o (75) * 100.00 / (32750) = 0.23 % % of P.v received treatment according to national guideline o (12181) * 100.00 / (14391) = 84.64 % 33

34. Artemisinin resistance Tiers in the GMS, as of June 2014 Tier I:  Areas for which there is credible evidence for artemisinin resistance  Surin, Srisaket, Trat, Ranong, Kanchanaburi, Tak Tier II:  Areas with significant inflows of mobile and migrant populations from tier I areas or shared borders with tier I areas, Tier III:  P. falciparum endemic areas which have no evidence of artemisinin resistance and have limited contact with tier I areas

35. Cambodia n 42-day ACPR-PCR Day 3 2008Pailin49100%26% VV, Pursat76100%8% 2009Pailin3892%33% Preah Vihear60100%5% Rattanakiri57100%0 2010Pailin2976%45% VV, Pursat5789%7% Rattanakiri60100%0 2011Snoul5696%20% Preah Vihear5997%8% VV, Pursat4283%36% 2012Battambang4069%15% VV, Pursat 2491%54% Kamp Thom 60100%27% Kamp Speu 22100%17% 2013-14 Kampot 1794% 44 Preah Vihear 1694%43.8% Kratie 22100%31.8% Rattanakiri 60100%13.3% DHA-PIPASU+MEF Thailand Total n 42-day PCR-ACPR Day 3 2008Mae Hong Son44100%5% Tak6597%0 Ratchaburi50100%0 Ranong4797%0 Ubonratchathani45100%0 Yala54100%0 2009MaeHongSon3392%9% Tak5690%14% Kanchanaburi5693%25% Ranong5287%17% 2010Tak3992%9% Ranong5291%5% Yala4998%0 Ratchaburi27100%5% 2012MaeHongSon1592%0% Kanchanaburi5475%48% Ubonratchathani888%13% 2013-2014Mae Hong Sonon-going Tak“ Ratchaburi“ DHA-PIP Kanchanaburi“

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40. Key technical partners WHO GF ATM US PMI/USAID, US CDC ACTmalaria APMEN Universities, e.g. Mahidol, Kasetsart Malaria Consortium Malaria Association of Thailand

41. 1. TES studied during 2004-2014 showed ATS-MQ somewhat decline dramatically in some province. 2. the First line treatment for Pf. has been changed to DHA-PIQ and Primaquine 3. Second line treatment is elucidative configured 4. Chloroquine is still effective to non-falciparum malaria ( Pv, Po, Pm.) 5. Drug policies are developed for uncomplicated, complicated, children and pregnant women. 5. Study of TES against malaria drugs is still going on periodically. Summary of Thailand-TES presentation

42. Thank you