ARTEMISININ BASED COMBINATION THERAPY FOR MALARIA IN CAMBODIA:HOW WELL IS IT BEING IMPLEMENTED?

1. ARTEMISININ BASED COMBINATION THERAPY FOR MALARIA IN CAMBODIA:HOW WELL IS IT BEING IMPLEMENTED? Yeung SM1,2, Socheat D3, Van Damme W4, Mills AM1, White NJ21. Health Policy Unit, London School of Hygiene and Tropical Medicine2. Wellcome Trust-Mahidol University, Oxford Tropical Medicine Research Programme3. National Malaria Centre, Cambodia4. MSF Cambodia

2. Overview • Background - Malaria in Cambodia • Study questions • Drug usage survey • Method • Summary of results • Modelling the effect on the development of resistance • Policy implications • Recommendations for research

3. Changed policy to artesunate and mefloquine (2001) Blister packaging Rapid diagnostic tests (RDTs) Village Malaria Volunteers /malaria outreach teams Social marketing of drug and RDTs Publicity campaign Cambodia STRATEGIES PROBLEMS • Multi-drug resistance • Poor provider and patient adherence • Inaccurate diagnosis • Informal sector • Fake drugs • Inaccessibility

4. Study questions How effectively has the policy of early diagnosis and treatment with ACTs been implemented in Cambodia? • Biological diagnosis prior to treatment? • Coverage with first line drug? • Provider compliance and patient adherence? • Improved access with village malaria workers and outreach? • What does this mean in terms of the development of drug resistance? • What are the costs to the patient and provider?

5. Methods • Qualitative study (in-depth interviews) • Household x-sectional survey • Inclusion criteria: • Anyone who took antimalarials or had symptoms of malaria in last 3 weeks • Questions: • Treatment seeking, diagnosis, drug usage (type, dose and duration), costs, socio-economic status • Blood tests: • Paracheck, Blood smear +/- Mefloquine level • Mathematical modelling of antimalarial drug resistance

6. Anlong Veng Sotnikum Malai Thmar Bang Chik Phat Selection Anlong Veng district – biweekly MSF “Malaria Outreach Teams” (MOTs) 4 other “typical districts” with no malaria-specific intervention Thmar Beng district – Village Malaria volunteers (VMVs) • Villages in each district stratified by accessibility and randomly selected

7. Summary of results The good news • High levels of patient adherence to the blister packaged artesunate and mefloquine (>80%) • Higher rates of biological confirmation prior to treatment with the first line drug than with other antimalarials (34% versus 5%) • Village malaria worker and malaria outreach teams greatly improved case management and reduced mean household cost per treatment episode (<10X).

8. The bad news • Low usage of formal sector (<12% of treatments) • Low rates of biological diagnosis prior to antimalarials (<20%) • The usual treatment from the informal sector • Most common antimalarial • Artemisinin “monotherapy” (25%) or Chloroquine (20%) • Only 5% of antimalarial treatments contained artesunate and mefloquine

9. …….. (continued!) • Most antimalarials taken for inadequate duration • 45% for chloroquine (3 days) and • 9% for artemisinin alone (7 days) and Quinine (7 days) • Most antimalarials not taken for malaria • Risk groups particularly poorly managed (ie children, pregnant women, complicated cases) • Leakage of drugs from public sector to private sector • Fake artesunate found

10. Implications for the development of drug resistance? • Results will be input into bio-economic model of antimalarial drug resistance along with other parameters: • Vectorial (anopheles density, biting rate ….) • Epidemiology and immunity (age stratified prevalence, parasite density, severity ….) • Drug (level of drug resistance, effect on transmission) • Behavioural (treatment seeking, drug choice, drug usage) • Economic (cost of treatment, cost of failure)

11. R=resistant to drug A S=sensitive to drug A Fail Not treated (ntr) Behaviour factors Asymptomatic Costs Cure Adherence Cost of diagnosis and treatment of “false positives” Access to treatment and treatment seeking behaviour Fail Cost of failures Cost of failures Infected Not infected Monotherapy (trA) Cure Inoculation rate Fail Symptomatic Parasite density Combination therapy (trAB) Vector factors Cost of first line treatments Cost of first line treatments Cure “Infectiousness”

12. Implications for policy and practice • Expansion of VMV scheme as means of improving case management  • Urgent reduction in the amount of artemisinin monotherapy use in informal sector: • “Stick” – regulation and enforcement ? • “Carrot” • Improve “behaviour change communication” () • Provide artemisinin combinations cheaper than monotherapy () • Switch to co-formulated product at earliest opportunity (probably Dihydroartemisinin-Piperaquine) ?

13. Increase uptake of biological diagnosis • More emphasis on RDTs during social marketing in communication and training • Reduce cost to patient compared to the drugs? • Single packets for RDTs? • Risk groups • Children – add guidelines for oral medication • Migrant workers - targeted strategy? • Formal sector

14. Recommendations for research Cambodia • Qualitative studies of informal sector and community to establish the “hows”, “whys” and “how to make it better?” • Evaluate the effect of current interventions (scaling up of VMV scheme and social marketing project) in Cambodia with pre- and post intervention drug usage studies Methods • Possible to assess which patients actually had malaria or not • Antigen testing or antibody testing on random subset of interviewees at time of interview in low prevalence areas • Improve validity of self-reported drug usage behaviour • Explore use of drug assays from urine/blood/saliva • Triangulate with data from exit interviews or “dummy patients”

15. Korp khun maak ka !

16. 100% Patient with PF malaria goes to health center 100 % Patient has a blood test 100% Provider prescribes A+M 100% The drug is correctly prescribed The patient takes the drug as prescribed 100% 100% The drug is good quality 100% The prescribed regime is effective

17. Patient with PF malaria goes to private sector 38% Patient has blood test 10% Provider prescribes A+M 80% The drug is correctly prescribed 80% The patient takes the drug as prescribed The drug is good quality 90% 95% The prescribed regime is effective 2 % receive “perfect management