1. Caroline Lynch & Jim Tulloch June 2014 Synthesis of current evidence on the multiple causes of malaria drug resistance

2. Overview 1.Why do drugs stop working? 2.What actions are potentially accelerating antimalarial resistance? 3.Update on artemisinin resistance. 4.Policy options.

3. Accidents during reproduction Mutations Helps parasite Hinders parasite No effect Susceptible parasite Parasite with mutations 1. Why do drugs stop working?

4. Treatment Drug selection for resistant parasites If parasites have a mutation which protects them from treatment they will survive. Susceptible parasites are eliminated - the drug has ‘selected’ resistant parasites. Resistant parasites will produce gametocytes which can be transmitted to mosquito. Susceptible and resistant parasites

5. Imagine a malaria-endemic village Drug pressure Antimalarial treatment Susceptible parasite Resistant parasite

6. What could contribute to drug pressure? A high proportion of the population with variable amounts of antimalarials in their bloodstream – how? o High malaria transmission o Too much treatment (overtreatment) o Too little treatment (undertreatment/ partial treatment).

7. Why too much treatment? Why too little treatment? Supply side 2. What actions are potentially accelerating antimalarial resistance? Supply side Treatment without diagnosis Demand side Patients seek treatment without diagnosis Availability of monotherapy (direct selection) and substandard antimalarials Partial treatment provided to patients Patients take partial treatment Demand side

8. Demographic factors Migration Chloroquine resistance Sulfadoxine-Pyrimethamine resistance Previously resistance emerged in GMS and spread. High mobility in GMS Increased ties with Africa High potential for spread of AR

9. 3. Update on artemisinin resistance Artemisinin resistance has been detected in all GMS countries. GPARC and regional containment strategies in place. In 2013; o Emergency Response to Artemisinin Resistance (ERAR). o Funds for artemisinin resistance containment. o Molecular marker (Kelch 13) identified.

10. 4. Policy options

11. Ban monotherapy and eliminate substandard antimalarials o Part of broader recommendation to improve regulatory capacity Facilitate cross-border surveillance & multisectoral collaboration. Establish agile and aggressive field team to support ERAR. Ensure immediate implementation of primaquine policy. Create flexible fund for specific, answerable questions around interim antimalarial dosing and treatment o Part of broader recommendation on funding for Operational Research Develop strong regional mechanisms for rapid response

12. Track and respond to artemisinin resistance Track : Immediately begin monitoring 1-2 artemisinin resistance indicators updated monthly by secretariat. Respond: Where countries are not on track – taskforce identify bottlenecks and provide immediate support to countries to find solutions. Ensure accountability & transparency

13. Advocate to the DG/WHO for AR to be reviewed - Public Health Emergency of International Health.  All avenues of advocacy Continue advocacy at regional level to ensure political support for technical frameworks for artemisinin resistance elimination o Part of broader recommendation for ongoing advocacy in support of malaria elimination High level collective advocacy

14. “A regional public health disaster which could have severe global consequences” (WHO, 2014) There is a window of opportunity if we act now