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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 Objectives of Presentation 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. 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 Burden of Infectious Diseases in Humans and Need for Antimicrobial Drugs 4 Total infectious disease deaths: 14.4 million each year 3.5 3 Millions of deaths in 2000 2.5 2 1.5 1 0.5 0 ARI HIV-AIDS DIARR. DISEASE TB MALARIA 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 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 Ideal Treatment of Infectious Diseases with Antimicrobial Drugs Infected patient 1. Trained health provider consulted Treatment failure or drug resistance 2. Specific diagnosis made 3. Correct drug prescribed in correct dose indicate a problem BUT 4. High-quality drug and treatment Treatment failure information obtained doesn’t always mean 5. Treatment regimen followed drug resistance Cured patient 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 The Treatment vs. Drug Resistance Dilemma Health Provider Priority Public Health Priority Client: patient (individual) Client: MoH (society) Objective: cure disease fast Objective: cure, limit AMR Possible consequence: more poor drug use Possible consequence: limited access to drugs Evidence that Treatment of Infectious Diseases Needs to be Improved Total : 11,754,000 Sources: 2001 World Health Report and WHO reports Outbreaks of Typhoid Fever (Salmonella typhi) Year(s) of Outbreak 1989 1990-95 1990-95 1990-93 1991 1991 1991-92 1992-94 1993-94 1994 1994-95 1996-97 Location Resistance Type Pakistan India Arabian Gulf Kuala Lumpur UK S. Africa Egypt Vietnam Philippines Bangladesh Pakistan Tajikistan ACSSuTTm ACSSuTTm ACSSuTTm ACSSuTTm CSTTm ACSSuT ACSSuTTm ACSSuTTm CKSSuTTm ACSSuTTm ACSSuTTm ACSuCi 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. Drug Resistance: Everyone’sSpread Problem Eventually of Chloroquine-Resistant Malaria from Cambodia (1960s) Spread of Chloroquine-Resistant Pf Malaria from Cambodia HEALTH & FITNESS Tuesday May 7, 2002 Section F, Page 5, Column 1 Since 1960: New Resistant • 6-fold increaseGonorrhea in global trade Migrating to Mainland U.S. National Institutes of Health • 17-fold increase in number of people travelling in airplanes Since 1980: Volume 334:933-938, Number 15 April 11, 1996 • 9-fold increase in number of refugees/displaced Transmissionpeople of MultidrugResistant Mycobacterium tuberculosis during a Long Airplane Flight Common Approach to Drug Resistance: Switch Drugs and Ignore Contributing Factors Cure Rate % 120 Treating P. falciparum malaria in Thailand $0.89 100 Mefloquine Current treatment: Mefloquine + artesunate 80 Quinine 60 40 Sulphadoxine- Cost: $ 3.59 per patient Total Pf cases: 62,000 Pyrimethamine 20 $0.10 0 Chloroquine 1975 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 Year Year Source: SE Asia J Trop Med Public Health 1999; 30: 68 Total M/A treatment cost: $222,000 (34X greater than CQ) Consequences of not Addressing Contributing Factors: Drug-Resistant TB MDR-TB SIERRA LEONE 1997 Any drug resistance other than MDR Susceptible THAILAND 1997 RUSSIA (Tomsk Oblast) 1999 1. Treatment 12-18 months (vs. 6 months) 2. Alternative drugs more toxic LATVIA 1998 3. Drug costs >$1,000 (vs. $10) RUSSIA (Ivanovo Oblast)1998 CHINA (Henan Province)1996 ESTONIA 1999 0% 20% 40% 60% 80% 100% Prevalence of Drug Resistance in New TB Cases Source: Anti-tuberculosis Drug Resistance in the World Report No.2. WHO 2000 Consequences of not Addressing Contributing Factors: Cost of TB Drugs Country Treatment (MDR rate in of: new cases) India (3.4%) Russia (6.0%) Notified SS+ cases 70% of estimated SS+ cases Notified SS+ cases 70% of estimated SS+ cases No With Increased cost MDR-TB MDR-TB due to MDR-TB $3.5 million $5.8 million $15.3 million $25.4 million $11.8 million $0.3 million $0.6 million $1.8 million $4.2 million $1.5 million Source of data: 2002 WHO Global Tuberculosis Control Report $19.6 million $3.6 million What Can Be Done to Address Drug Resistance in Developing Countries? WHO Strategy (http://www.who.int/emc/amr.html) 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 USAID AMR Activities What Can Be Done to Improve Treatment in Developing Countries? • 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 Improved Procurement of TB Drugs: Example from Kazakhstan Types of TB drugs procured in 1998 non-DOTS 73% DOTS 27% Types of TB drugs procured after 1999 tender with RPM assistance DOTS+ (MDR) 17% DOTS 83% 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 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 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: http://www.usaid.gov/pop_health/id/amr/publications/docs/amrstrategies.doc USAID AMR Partners Include... • 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 Accessible to missions through existing GH agreements USG Interagency Task Force on Antimicrobial Resistance Agency for Healthcare Research and Quality Centers for Medicare and Medicaid Services Health Resources and Services Administration Agency for International Development Department of Defense Department of Agriculture Environmental Protection Agency Department of Veterans Affairs Things to Remember about Drug Resistance 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.