Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Regional Framework for Artemisinin Resistance Containment A Working Document Charles Delacollette

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Roll Back Malaria Objectives Proposed in 1999 in the GMS - to reduce malaria mortality (50% reduction in 2010 as compared to 1998) - to significantly reduce malaria morbidity (no suggested % of reduction) - to attain or maintain acceptable level of parasite resistance to antimalarial medicines in all endemic falciparum malaria areas (ACPR of first line antimalarial medicines above 90%) Ho Chi Minh City, Viet Nam, 3-4 March 1999

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Malaria Mortality Trends (From MOH through WHO) Myanmar Cambodia Thailand Viet Nam Lao PDR China

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April Pf (%)2010Pf (%) Myanmar104,753 >80 420,808>90 Cambodia58,874>90 49,356>80 Thailand131,055>5032,502>50 Viet Nam72,091>7017,515>80 Lao PDR39,031>95 20,800>95 China (Yunnan)27,090<2013,055<20 Confirmed malaria cases in the Greater Mekong Subregion in 1998 and 2010 [MOH data through WHO]

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Control to elimination continuum

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Pailin Trat Ninh Thuan Preah Vihear Quang Tri Dak Nong Binh Phuoc Ranong Tak Luang Prabang Bago Menglian Kanchanaburi Kawthaung Kyaing Tone Yingjiang Mae Hong Son Kalay Sentinel Sites ( ) 1. Cambodia 1.1 Rattanakiri 1.2 Preah Vihear 1.3 Pailin 1.4 Pursat 1.5. Snoul 2. China 2.1 (Menglian, Yunnan) 2.2 Yingjiang, Yunnan 2.3 Tengchong, Yunnan 3. Lao PDR 3.1 Khammoune 3.2 Attapeu / Champassak 3.3 (Luang Namtha / L Prabang) 4. Myanmar 4.1 Myit Kin Nar, Kachin 4.2 Shwe Kyin, Bago 4.3 Kawthaung, Thanintharyi 4.4 Kalay, Sagaing 4.5 Myawaddy, Kayin 4.6 Tanphyuzayat, Mon 4.7 Kyauk Taw, Rakhine 4.8 Kyaing Tone, Eastern Shan 5. Thailand 5.1 Tak 5.2 Kanchanaburi 5.3 Mae Hong Son 5.4 Ranong 5.5 Chanthaburi 5.6 Yala 5.7 Ubon Ratchathani 5.8 Trat 6. Viet Nam 6.1 Quang Tri 6.2 Dak Nong 6.3 Binh Phuoc 6.4 Ninh Thuan 6.5 Gia Lai Rattanakiri Chantaburi Yala Attapeu Khammoune MEKONG TES NETWORK Pursat Myit Kin Nar Mon Myawaddy Rakhine Ubon Ratchathani Gia Lai Jiangsu New sites for Surin, Thailand - Bhamo, Kachin, MMR - Kayah, MMR Tengchong

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Definition of Early Treatment Failure (ETF) : Day 1-3  danger signs or severe malaria on day 1, 2 or 3 in the presence of parasitaemia;  parasitaemia on day 2 higher than on day 0, irrespective of axillary temperature;  parasitaemia on day 3 with axillary temperature ≥ 37.5 ºC;  parasitaemia on day 3 ≥ 25% of count on day 0. WHO. Susceptibility of Plasmodium falciparum to antimalarial drugs. Report on global monitoring 1996–2004. Geneva, World Health Organization, 2005 (WHO/HTM/MAL/ ) (

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Definition of Late Treatment Failure (LTF) : Day 7-28/42 Late clinical failure  danger signs or severe malaria in the presence of parasitaemia on any day between day 4 and day 28 (day 42) in patients who did not previously meet any of the criteria of early treatment failure;  presence of parasitaemia on any day between day 4 and day 28 (day 42) with axillary temperature ≥ 37.5 ºC (or history of fever) in patients who did not previously meet any of the criteria of early treatment failure Late parasitological failure  presence of parasitaemia on any day between day 7 and day 28 (day 42) with axillary temperature < 37.5 ºC in patients who did not previously meet any of the criteria of early treatment failure or late clinical failure WHO. Susceptibility of Plasmodium falciparum to antimalarial drugs. Report on global monitoring 1996–2004. Geneva, World Health Organization, 2005 (WHO/HTM/MAL/ ) (

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Definition of Adequate Clinical and Parasitological Response (ACPR)  absence of parasitaemia on day 28 (day 42), irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure WHO. Susceptibility of Plasmodium falciparum to antimalarial drugs. Report on global monitoring 1996–2004. Geneva, World Health Organization, 2005 (WHO/HTM/MAL/ ) (

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Working definition of As R The working definition of artemisinin resistance is based on clinical and parasitological outcomes observed during routine therapeutic efficacy studies of ACTs and clinical trials of artesunate monotherapy:  an increase in parasite clearance time, as evidenced by  10% of cases with parasites detectable on day 3 after treatment with an ACT (suspected resistance)  Or  treatment failure after treatment with an oral artemisinin-based monotherapy with adequate antimalarial blood concentration, as evidenced by the persistence of parasites for 7 days, or the presence of parasites at day 3 and recrudescence within 28/42 days (confirmed resistance).

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Percentage of treatment failure of different ACTs in Greater Mekong Sub-region, Global Malaria Report 2010 Trat Updates: June 2011 Pailin DHA-PIP Trat A+M (containment zone)

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Percentage of positive cases on Day 3 after ACT in the Greater Mekong Sub-region, Global Malaria Report 2010 Binh Phuoc Updates, June 2011 Viet Nam Binh Phuoc: DHA-PIP Myanmar Mon DHA-PIP Tanintharyi DHA-PIP Cambodia Pailin DHA-PIP Thailand Trat A+M Trat Updates: Dec 2011 Pailin A+M * Surin/Sisaket A+M (containment Zone 2)

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Phuoc Long Eastern Shan

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Qinghaosu - Artemisinins Rapid action, broad stage specificity, safe, gametocytocidal

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012  Limited access to (and use of) quality diagnosis and quality medicines including adherence to Treatment by vulnerable population (mobile pop and migrants, ethnic groups … ) or due to occupational risk situations (development projects, forest, …)  Marketing and Use of Monotherapies, Counterfeits and Substandard Medicines  Private Sector Engagement to adhere to best practices  Lack of direction and coordination to boost harmonized activities  Lack of support to operational research (alongside with programmes)  Declining interest of Governments and Donors (competing priorities) Potential Contributing Factors to As resistance and impacting on Malaria Elimination Possibly better addressed through a Regional Response

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Cross-border Migration in GMS India Bangladesh Malaysia Cambodia China Vietnam Indonesia Myanmar Thailand Laos

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Definition of tiers Tier I: Areas for which there is credible evidence of artemisinin resistance 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 limited contact with tier I areas

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 What to do? Summary of recommendations by Tier. Tier III Good Control More routine monitoring Eliminate monotherapies & poor-quality drugs Tier II Intensified & accelerated control Intensified monitoring, esp. on border near foci Actively eliminate monotherapies & poor-quality drugs Lower transmission; focus on mobile & migrant populations Tier I Intensified & accelerated control to universal coverage Intensified monitoring, esp. around foci Aggressively eliminate monotherapies & poor-quality drugs Lower transmission; focus on mobile & migrant populations Consider ACD, MSAT, FSAT or MDA

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Goal of the Regional Framework The goal of the Regional Framework is to contribute to the global effort to protect ACTs as an effective treatment for falciparum malaria and contribute to the health of the population in the Greater Mekong Subregion.

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Objectives DRAFT

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April Coordination of an intensified containment effort 2.Raise awareness at every level, build political support and secure adequate financial resources 3.Support mapping of the extent of the artemisinin resistance problem, and expand and strengthen monitoring and evaluation 4.Promote access to and rational use of quality assured, safe, effective antimalarials and diagnostics, including support for intensive action against oral artemisinin-based monotherapies and substandard and counterfeit antimalarial medicines 5.Increase the use of appropriate vector control measures 6.Support rapid implementation of special measures for high- risk occupational groups and migrant/mobile populations 7.Support and coordinate containment specific research and development of new tools

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Main activities by regional objective Indicators M&E plan Budget

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012 Group work a)to endorse the joint strategic assessment of the Response to AR in the GMS and b)to provide with inputs in the draft Regional Framework for Artemisinin Resistance Containment.

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, April 2012