Bureau of Vector Borne Disease Control, Thailand. TES result in

1. to report the evaluation of the current first-line treatment for uncomplicated P. falciparum, in Thailand( during ) 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

Malaria morbidity rate per 1000 population during Rate Fiscal year Eliminating Option Morbidity rate< 1/ 1000 population

Malaria elimination phase in Thailand 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

Confirmed Malaria Cases and Deaths (FY ) No. of Cases Fiscal year Thai death

Percentage Fiscal Year Proportion of Malaria Parasites Species, Source: BVBD

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

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

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

Summary of ACPR of ATS-MQ during

Summary of EFT ( D3 Pos) of ATS-MQ during

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

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 Source: therapeutic efficacy monitoring

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

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 (preliminary results) 90% and above 80-89% 50-79% 49% and lower ACPR %

ACPR and D3 positive Chloroquine (CQ) Vivax malaria (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)

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

P. falciparumTakRanongRatchaburiYalaTotal Enrolled Lost follow up or excluded Analyzed 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

P. falciparumMHKNUBSUTotal Enrolled Lost follow up or excluded Analyzed Treatment outcome: ETF00000 LCF018.6%(8) %(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) D %(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),

P. falciparumRNTKTotal Enrolled Lost follow up or excluded Analyzed 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),

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)

TES sentinel sites in Thailand Informative source: BVBD 11 Feb 15 AS/MQ DHA/piq PYR/AS CHL

Antimalaria drug resistance in Thailand Plasmodium falciparum 1: ปี : ปี : ปี : ปี % ACPR

Antimalaria drug resistance in Thailand Plasmodium vivax 1: ปี : ปี % ACPR

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

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)

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

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

Antimalarial Drugs Adverse Reactions,as of Nov 2014 YearArtesunateNon- Artesunate Total Source : Thai FDA

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

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

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

Cambodia n 42-day ACPR-PCR Day Pailin49100%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% 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 Mae 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% Mae Hong Sonon-going Tak“ Ratchaburi“ DHA-PIP Kanchanaburi“

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

1. TES studied during 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

Thank you