1. Controlling Drug Resistance in Developing Countries USAID Antimicrobial Resistance (AMR) Working Group* ANE/E+E SOTA, October 2002 *Includes: Neal Brandes, Tony Boni, Andrew Clements, Ruth Frischer, Marni Sommer, Cheri Vincent

2. Highlight the complexity of the drug resistance problem and its impact on controlling infectious diseases and USAID PHN programs. Provide information on country-level approaches to control drug resistance and what assistance is available from USAID/W. Objectives of Presentation

3. Antimicrobial Drugs Specifically kill or inhibit growth of microbes: viruses, bacteria, fungi, parasites Key tools for treating infectious diseases: humans, animals, plants Lose efficacy over time if used inappropriately

4. Burden of Infectious Diseases in Humans and Need for Antimicrobial Drugs Estimated number of infections: TB -- 2 billion total (9 million new cases per year) Malaria -- 300-500 million new cases per year HIV/AIDS -- 40 million total (5 million new cases per year) Sources: 2001 World Health Report, 2002 UNAIDS Report, 2002 Global TB Control Report, and other WHO reports Millions of deaths in 2000 Total infectious disease deaths: 14.4 million each year

5. Ideal Response to Infectious Diseases Prevention immunizations hygiene, safe water/food infection control in hospitals insecticide-treated materials and/or vector control condoms other behavior changes Treatment rational use of high-quality antimicrobial drugs Public Sector Private Sector and NGOs Global Initiatives e.g. RBM, GDF, GFATM, Trachoma

6. Ideal Treatment of Infectious Diseases with Antimicrobial Drugs Infected patient Cured patient 1. Trained health provider consulted 2. Specific diagnosis made 3. Correct drug prescribed in correct dose 4. High-quality drug and treatment information obtained 5. Treatment regimen followed Treatment failure or drug resistance indicate a problem BUT Treatment failure doesnt always mean drug resistance

7. Challenges to Treating Infectious Diseases with Correct Dose of Appropriate Drug Poor drug use Poor drug quality Fake Artesunate in Southeast Asia Lancet, Vol. 357, June 16, 2001 Shops in Burma, Cambodia, Laos, Thailand, Vietnam: 38% of artesunate samples contained no drug Private sector Fills in where reach of public sector is limited Producing/exporting antimicrobial drugs

8. The Treatment vs. Drug Resistance Dilemma Health Provider Priority Client: patient (individual) Objective: cure disease fast Possible consequence: more poor drug use Public Health Priority Client: MoH (society) Objective: cure, limit AMR Possible consequence: limited access to drugs

9. Evidence that Treatment of Infectious Diseases Needs to be Improved Sources: 2001 World Health Report and WHO reports Total : 11,754,000

10. Outbreaks of Typhoid Fever (Salmonella typhi) A=Ampicillin; C=Chloramphenicol; S=Streptomycin; Su=Sulphonamide; T=Tetracycline; Tm=Trimethoprim. Reference: Rowe et al. Clin Infect Dis 1997, 24(Suppl 1):S106-9.

11. Since 1960: 6-fold increase in global trade 17-fold increase in number of people travelling in airplanes Since 1980: 9-fold increase in number of refugees/displaced people Spread of Chloroquine-Resistant Pf Malaria from Cambodia National Institutes of Health HEALTH & FITNESS Tuesday May 7, 2002 Section F, Page 5, Column 1 New Resistant Gonorrhea Migrating to Mainland U.S. Volume 334:933-938, Number 15 April 11, 1996 Transmission of Multidrug- Resistant Mycobacterium tuberculosis during a Long Airplane Flight Drug Resistance: Everyones Problem Eventually

12. Common Approach to Drug Resistance: Switch Drugs and Ignore Contributing Factors Source: SE Asia J Trop Med Public Health 1999; 30: 68 Treating P. falciparum malaria in Thailand Year Cure Rate (%) $0.10 $0.89 Current treatment: Mefloquine + artesunate Cost: $ 3.59 per patient Total Pf cases: 62,000 Total M/A treatment cost: $222,000 (34X greater than CQ)

13. Consequences of not Addressing Contributing Factors: Drug-Resistant TB Source: Anti-tuberculosis Drug Resistance in the World Report No.2. WHO 2000 1. Treatment 12-18 months (vs. 6 months) 2. Alternative drugs more toxic 3. Drug costs >$1,000 (vs. $10) Prevalence of Drug Resistance in New TB Cases

14. Consequences of not Addressing Contributing Factors: Cost of TB Drugs Source of data: 2002 WHO Global Tuberculosis Control Report

15. WHO Strategy 1. Support prevention programs to reduce the need for antimicrobial drugs 2. Improve treatment of infectious diseases to reduce emergence of drug resistance Approach: promote rational use of drugs assure good-quality drugs are available when and where needed What Can Be Done to Address Drug Resistance in Developing Countries? USAID AMR Activities (http://www.who.int/emc/amr.html)

16. Promote rational drug use through strategies such as IMCI and DOTS Monitor drug resistance, drug-use practices, drug quality to assess PHN program performance and follow trends Support advocacy/communications to mobilize resources and coordinate efforts Develop/target interventions based on monitoring data to: -- train health and lab staff: drug use and quality, infection control, surveillance (see above) -- educate consumers: care-seeking, treatment compliance -- improve drug policy/regulation/management: use, quality, access What Can Be Done to Improve Treatment in Developing Countries?

17. Improved Procurement of TB Drugs: Example from Kazakhstan Types of TB drugs procured in 1998 Types of TB drugs procured after 1999 tender with RPM assistance

18. Integrated Response to Drug Resistance: An Example from Cambodia Malaria prevention and treatment for at-risk populations: Bednets Rapid diagnostics Pre-packaged combination therapy (public and private sector) Surveillance of drug resistance, drug quality, drug-use practices Patient/provider education (bednets, therapy, drug quality) Partnerships: Funded by GH, ANE Bureau, Cambodia mission, EU, Japan Implemented by WHO/Cambodia, National Malaria Centre Additional training, technical assistance from WHO/WPRO, ACTMalaria, CDC, RPMPlus, USPDQI Note: some parallel activities in Thailand, other Mekong countries

19. USAID/GH Support for a Country-Level Pilot Program to Contain Drug Resistance Objective: Develop and implement a rational, prioritized, and coordinated action plan to control drug resistance in developing countries Proposed approach (GH to fund pilot in 1-2 countries): Assess resistance problem, available resources/partners/capacity Prioritize areas for action (diseases, PHC, hospitals, consumers, providers, public sector/private sector) Monitor and evaluate interventions Disseminate findings

20. Other Illustrative USAID Activities (Global/Regional/Country) Advocacy and communication: Development of WHO Global AMR Strategy Increasing awareness of drug resistance problem,impact of new global initiatives (e.g. GFATM) Surveillance: Improving monitoring of resistance, drug quality, and drug use Drug management/use/quality/etc.: Training on rational drug use, drug procurement Collecting information on drug quality in ANE region Research: Improving drug-use behaviors, drug regimens Developing new tools for monitoring drug quality, drug use For more details see: h ttp://www.usaid.gov/pop_health/id/amr/publications/docs/amrstrategies.doc

21. Academy for Educational Development Alliance for the Prudent Use of Antibiotics Boston University Centers for Disease Control and Prevention ICDDR,B International Clinical Epidemiology Network Johns Hopkins University Management Sciences for Health U.S. Pharmacopeia World Health Organization Other global/regional/national/local organizations USAID AMR Partners Include... Accessible to missions through existing GH agreements

22. USG Interagency Task Force on Antimicrobial Resistance Department of Defense Environmental Protection Agency Agency for Healthcare Research and Quality Centers for Medicare and Medicaid Services Health Resources and Services Administration Department of Agriculture Department of Veterans Affairs Agency for International Development

23. 1. Drug resistance will be a constant threat as long as infectious diseases are present and treated with antimicrobial drugs. Rate of emergence will be faster with poor drug use/ quality. 2. Monitoring drug resistance, drug use practices, and drug quality through existing disease-treatment programs provides valuable feedback on program performance. 3. USAID/W is available to provide technical assistance (and some funding) to support missions in addressing drug resistance. Things to Remember about Drug Resistance