The global challenge of antimalarial drug resistance MMV Stakeholders Meeting New Delhi, India 8 November 2012 Robert D. Newman, MD, MPH Director, Global Malaria Programme newmanr@who.int
AR Situation Response Risks Conclusions
AR Situation
Artemisinin Resistance: day-3 positivity post-act Eastern Shan WHO 2010 Phuoc Long from 2010 report new data
Day-3 positivity post-act, Cambodia & Viet Nam 2006-2011 THAILAND LAOS Ubon Rachathani AM Battambang AM AM AM DP Preah Vihear Ratanakiri AM DP Gai Lai DP DP AL: artesunate-lumefantrine; AM: artesunate-mefloquine; DP: dihydroartemisinin-piperaquine DP AM DP DP Pailin DP Pursat Kampot AM CAMBODIA Kratie AM AM Dak Nong DP Binh Phouc DP VIET NAM > 3 Percentage of positive cases on day 3 3 9.9 10 19.9 20 39.9 40
Day-3 positivity post-act, Myanmar & Thailand, 2007-2011 MYANMAR Bago DP AL Mae Hong Son AM THAILAND Kayin Tak AL AL AM AM AA Mon AL DP Kanchanaburi AM Ratchaburi AM AM Percentage of positive cases on day 3 > 3 3 9.9 10 19.9 20 39.9 40 AA: artesunate-amodiaquine; AL: artesunate-lumefantrine; AM: artesunate-mefloquine; DP: dihydroartemisinin-piperaquine Tanintharyi AL AL DP DP Ranong AM AM
Response
Number of symptomatic Pf cases decreasing in Pailin, but... ARCE interventions begin 2008 2009 2010 2011 2012
Global Plan for Artemisinin Resistance Containment (GPARC): January 2011 Contain or eliminate artemisinin resistance where it already exists Prevent artemisinin resistance where it has not yet appeared 1 2 3 4 Stop the spread of resistant parasites Increase monitoring & surveillance to evaluate the AR threat Improve access to diagnostics & rational treatment with ACTs Invest in artemisinin resistancerelated research 5 Motivate action and mobilize resources
"One of the major threats to sustained malaria control and elimination is the emergence of malaria parasites that are resistant to artemisinins." Dr. Margaret Chan, Director-General World Health Organization 11 January, 2011
Scope of AR containment activities Myanmar Viet Nam Thailand Cambodia Tier I Tier I (inactive) Tier II Tier II (inactive)
Cambodian Justice Police, western Cambodia
Focused Screening and Treatment, Western Cambodia
Map of Myanmar townships by Tier 1-3
Myanmar Artemisinin Resistance Containment Plan (MARC) Objective 1: Improve access to and use of early diagnosis & quality treatment according to national treatment guidelines Objective 2: Decrease drug pressure for selection of artemisinin resistant malaria parasites by stopping use of artemisinin mono-therapies & sub-standard/fake drugs Objective 3: Limit transmission of malaria by vector control and personal protection Objective 4: Increase migrant/mobile populations access to and use of malaria diagnosis, treatment and vector control measures including personal protection Objective 5: Support containment of artemisinin resistant parasites through advocacy and BCC/IEC Objective 6: Conduct studies, especially operational research to support development of evidence-based containment policies and strategies Objective 7: Provide effective management and coordination to enable rapid & high quality implementation of the containment strategy
Focused Screening and Treatment, Western Cambodia Sub-clinic of Palm Oil Company Clinic in Kawthung, Myanmar
Cambodian Justice Police, western Cambodia Therapeutic Efficacy Training, West Africa 2010
TEG on Drug Resistance & Containment has called for development of GMS Emergency Response Plan for Artemisinin Resistance; Polio Emergency Action Plan a potential model
Malaria Policy Advisory Committee ERG a Evidence Review Groups ERG c Standing TEG on Malaria Vector Control ERG b Standing TEG on Chemotherapy Standing TEG on Drug Resistance & Containment WHO COs SAGE MPAC WHO DG WHO malaria policy recommendations and guidelines MoH and NMCPs Other WHO departments JTEG (with IVB) WHO GMP Secretariat WHO ROs RBM: Secretariat, WGs and SRNs VCAG (with NTD)
WHO recommendation on primaquine In: 1) areas threatened by artemisinin resistance where single dose primaquine as a gametocytocide for P. falciparum malaria is not being implemented, and 2) elimination areas which have not yet adopted primaquine as a gametocytocide for falciparum malaria: A single 0.25 mg base/kg primaquine dose should be given to all patients with parasitologically-confirmed falciparum malaria on the first day of treatment in addition to an ACT, except for pregnant women and infants <1 year of age
Research priorities for AR New drugs Molecular marker(s) for AR Mass drug administration for elimination of AR parasites Personal protection for special population groups Diagnostics for low density parasitemia Multiple first-line therapies Modeling: impact of AR; effect of containment efforts including new tools
Risks
Partner drugs artemether-lumefantrine artesunate-amodiquine artesunate-sp artesunate-mefloquine dihydroartemisinin-piperaquine artesunate-pyronaridine
MPAC recommendations on malaria case management in the private sector Access to affordable and quality assured malaria diagnostic testing, notably RDTs, should be an integral part of all initiatives aiming at improving access to ACTs in both the private and the public sectors In designing new initiatives on malaria case management in the private sector, the increased risk of selection and spread of antimalarial drug resistance (to both artemisinins and partner medicines) should be considered, and measures put in place to ensure targeting of ACTs to true malaria patients in need The priority for access to subsidized medicines and diagnostics should be given to children All future initiatives including subsidies for ACTs and RDTs should be designed with careful attention to mechanisms to ensure sustainability
Spread of chloroquine resistant Pf
What is at stake? Annual deaths (M) 4 Treatment: Quinine only 3 2 Americas Heavy use of DDT spraying Growing drug resistance S. Asia & Middle East Increase in control efforts 1 China & NE Asia? 0 1900 Africa 1920 1940 1960 1980 2000 Source: R. Carter and K. Mendis (2002). Evolutionary and historical aspects of the burden of malaria. Clinical Microbiological Reviews, 15(4): 564 594 ; Malaria R&D Alliance; WHO World Health Report (2004); WHO The Global Burden of Disease (2004); WHO World Malaria Report (2008); WHO World Malaria Report (2009)
Conclusions
Artemisinin Resistance, 2012 Current situation represents major threat to global malaria control & elimination efforts Should not overshadow tremendous overall success Urgent need to fully fund a GMS Emergency Response Plan for Artemisinin Resistance Need data on new approaches, e.g. MDA No evidence of artemisinin resistance in Africa Not an excuse for complacency Global implementation of T3: Test. Treat. Track. essential to preventing spread of antimalarial drug resistance
Focused Screening and Treatment, Western Cambodia