Global Antimalarial Drug Resistance Management and Containment Strategies Challenges & responses for malaria in Asia 15th RBM Partnership Board Meeting New Delhi, India, 10th November 2008 Dr Kamini Mendis WHO Global Malaria Programme 1

The situation today P.falciparum has developed a tolerance to artemisinins at the Cambodia-Thailand border – which will progress to resistance if not contained. Most of the antimalarials of the past have been lost to resistance Today the world is entirely dependent on artemisinins for the treatment of falciparum malaria

75 countries have adopted ACTs Countries which need ACT policy Countries which adopted ACT Countries Deploying ACTs Countries with ACTs at Community level Update: May 2008

The situation today P.falciparum has developed a tolerance to artemisinins at the Cambodia-Thailand border – which will progress to resistance if not contained. Almost all antimalarials of the past have been lost to resistance Today the world is entirely dependent on artemisinins for the treatment of falciparum malaria No replacements for artemisinins in the late pipeline of development

Pipeline of new antimalarial medicines up to 2010 AS-MQ 2010 2009 2008 2007 co-blistered products AS-AQ CD-AS (CDA) DHA-PPQ Paediatric Coartem™ Pyronaridine-AS Pyramax™ Art-Naphthoquine Art-PPQ < 2006 Fixed-dose combinations artemether-lumefantrine X Alternatives to artemisinin + ?

How best can we delay the onset and spread of drug resistance? Early detection of tolerance / resistance to artemisinins Routinely monitor therapeutic efficacy of ACTs In vivo studies on ACTs and artesunate WHO supported routine surveillance of drug resistance Standardized methodologies, tools and technical assistance To countries and regional and sub-regional networks

WHO/GMP has developed standardised methodologies 2007 2008 2003 2004 Updated 2008 New report in 2009 Planned: guidelines on pharmacokinetic and molecular markers for drug resistance

TET is important specially where SP and AQ are partner medicines Regional and sub-regional networks on monitoring drug efficacy Mekong TET is important specially where SP and AQ are partner medicines RAVREDA HANMAT

Strategies to prolong the life of Artemisinins Use of combination medicines – and prevent the use of AS by itself Withdraw oral artemisinin monotherapeis from market

January 2006

Steps to implement WHO recommendations 19 January 2006 – WHO Press Release Monitoring marketing practices and position of NDRA Dissemination of WHO position via WHO Offices, WHO staff briefings, inter-country and regional meetings with MOH officials 19 April 2006 – WHO technical briefing on malaria guidelines and artemisinin monotherapies Alignment of funding and procurement agencies 23 May 2007 - WHA Resolution 60.18 24 August 2007 – WHO informal consultation with manufacturers of artemisinin-based antimalarials WHO country meetings with pharmaceutical companies (India, China, Pakistan, Viet Nam) Monitoring system on http://malaria.who.int/

Manufacturers of oral artemisinin monotherapies: 12/67 (18%) withdrew their products 22/67 (33%) intend to comply with WHO ban Number of companies Substandard Medicines ?

National Drug Regulatory Authorities No. countries marketing oral artemisinin monotherapies Risk of developing resistance 2006 2007 2008

Strategies to prolong the life of Artemisinins Use of combination medicines – discontinue the use of AS alone Withdraw oral artemisinin monotherapeis from market

Access to medicines Availability of any antimalarial medicine and ACTs to children with fever, 2006–2007 (DHS, MICS, MIS surveys)

Strategies to prolong the life of Artemisinins Use of combination medicines – discontinue the use of AS alone Withdraw oral artemisinin monotherapeis from market Improve access to ACTs & parasitological confirmation of diagnosis Reducing transmission rates To lower the risk of spreading mutant resistant parasites

Main challenges Weak surveillance systems to monitor therapeutic efficacy of ACTs in countries Companies non responsive to request to withdraw marketting of monotherapies Poorly regulated pharmaceutical market in endemic countries Limited access to ACT: i) slow roll-out of ACTs in the public sector and ii) limited penetration of ACTs in the private sector Manufacturing of sub-standard products exploiting "niche market" left open by companies complying with WHO recommendations Need for multiple sources of information for monitoring

To avoid artemisinin resistance…. Correct policies in place Support implementation of strategies including with necessary funding Effective Government regulation Co-operation from the pharmaceutical sector Supportive action by all partners