Antimicrobial Drugs and Infectious Disease Initiatives: Increasing Drug Access while Containing Drug Resistance MAQ M

1. Antimicrobial Drugs and Infectious Disease Initiatives: Increasing Drug Access while Containing Drug Resistance MAQ Mini-University May 12, 2003

2. Burden of Infectious Diseases in Humans: Deaths (14.9 million in 2001) All Others 17% ARI 27% Which six diseases cause 83% of all infectious disease deaths worldwide? Measles 5% Malaria 8% TB 11% HIV/AIDS 19% Diarrheal Disease 13% Source: 2002 World Health Report

3. Burden of Infectious Diseases in Humans: Deaths (14.9 million in 2001) Geographic Distribution Americas, Europe, Eurasia 7% Why do almost all infectious disease deaths occur in developing countries? Africa, Middle East, South/Southeast Asia, Pacific 93% Source: 2002 World Health Report

4. Burden of Infectious Diseases in Humans: Infections Implications for disease control and development? Sources: 2002 World Health Report, 2002 UNAIDS Report, 2002 Global TB Control Report, and other WHO reports

5. Lessons Learned from the U.S. Infectious Disease Death Rate* 1900-1996+ What lessons apply to the control of infectious diseases worldwide? • 75% decrease (1900-1940) before widespread antibiotic, vaccine use. •  Need more than tools, technology (e.g. public health, education, etc.) • Increase (1980-1996) due to HIV/AIDS and drug-resistant TB. •  New tools need to be generated.

6. Concern about ID Burden and Availability of Effective Tools has led to Creation of GLOBAL INITIATIVES including: • Global Fund to Fight AIDS, TB, and Malaria • STOP TB/Global Drug Facility • Roll Back Malaria • PMTCT • A key component of each is increasing access toantimicrobial drugs for treatment.

7. Antimicrobial Drugs • Specifically kill or inhibit growth of microbes: • Illustrative examples: • viruses: HIV, hepatitis • bacteria: tuberculosis, some pneumonia and • diarrheal disease • parasites: malaria • fungi: thrush (yeast) • Key tools for treating infectious diseases: • humans, animals, plants • Lose efficacy over time if used inappropriately

8. Other Tools and Technologies Available to Control Infectious Diseases • Prevention • immunizations • hygiene, safe water/food • infection control in hospitals • insecticide-treated materials and/or insect control • condoms • other behavior changes • Treatment • diagnostics • antimicrobial drugs What tools are currently available? For most of these tools, failure to use properly does not have any negative consequences on long-term efficacy….

9. For essential medicines, we want to improve ACCESS,but… we also want to make sure these medicines are USED PROPERLY to avoid the development of drug resistance • so that medicines will remain effective to: • benefit more people over the long term • avoid toxicity, higher cost, complexity of • secondary drug regimens.

10. Failure to Use Drugs Properly: Treating P. falciparum Malaria in Thailand $0.89 Original treatment: Chloroquine, $0.10 per patient Current treatment: Mefloquine + artesunate, $3.59 per patient Higher treatment cost can limit access Cure Rate (%) $0.10 Year Source: SE Asia J Trop Med Public Health 1999; 30: 68

11. Failure to Use Drug Properly: Treating Drug-Resistant Tuberculosis 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 Source: Anti-tuberculosis Drug Resistance in the World Report No.2. WHO 2000

12. Predictions for HIV/AIDS and Potential for Drug Resistance • In 2002, 40 million HIV infections (UNAIDS) • In 2010, 50-75 million HIV infections predicted for 5 countries: China, Ethiopia, India, Nigeria, and Russia (National Intelligence Council) “Drug-resistant strains are likely to spread because of the inconsistent use of antiretroviral therapies and the manufacture overseas of unregulated, substandard drugs.“

13. Drug Resistance is a Global Phenomenon 12-55% ??? 5-95% 2-39% 30-50% Up to 98% Total : 11,604,000 Sources: 2002 World Health Report and WHO reports • Indicates that: • appropriate use of antimicrobial drugs is a challenge; • containment of drug resistance is difficult

14. Here Today, There Tomorrow HEALTH & FITNESS Tuesday May 7, 2002 Section F, Page 5, Column 1 New Resistant Gonorrhea Migrating to Mainland U.S. Spread of Chloroquine-Resistant Pf Malaria from Cambodia National Institutes of Health Volume 334:933-938, Number 15 April 11, 1996 Transmission of Multidrug-Resistant Mycobacterium tuberculosis during a Long Airplane Flight

15. Increasing access to drugs while preventing resistance requires a balancing act between: Patient Good: Increasing Access to Cure/Treat Public Health: Containing Resistance To Preserve Drug Efficacy

16. Are we trying to save lives, save drugs, or both? How many deaths are we willing to accept in order to prevent resistance? How much future drug resistance (and future deaths) are we willing to risk in order to prevent deaths now? What are the implications of finding ourselves in some middle ground?

17. Why is appropriate use of antimicrobial drugs such a challenge in developing countries?

18. Treating Malaria in Southeast Asia Conditions: Consequences: Malaria common in poor, rural, border Care seeking mostly in private sector, areas (government services limited) households paying for most services Substantial population movement Limited access to health care, limited driven by conflict ability to follow up to ensure cure Poorly regulated sales of antimalarial Incorrect drug or dosing contribute drugs in private sector to drug resistance Self-medication and poor patient Incorrect drug or dosing contribute compliance with treatment regimen to drug resistance Poor regulation and quality of locally- Incorrect dosing contributes to drug produced antimalarial drugs resistance Note: most of these conditions also affect other countries and infectious diseases

19. So when increasing access to drugs to treat infectious diseases Also need to consider….

20. Other Essential Investments in Health Systems to Complement Increased Access of Medicines 1. Patient education to improve care seeking behavior and treatment compliance. 2. Provider education to improve diagnosis and prescription of correct drug in correct dose and follow up to confirm cure. 3. Drug management and regulation to ensure high-quality drugs and treatment information available to both providers and patients. 4. Public health measures to prevent disease transmission. 5. Monitoring drug resistance to ensure only efficacious drugs recommended for treatment. Infected patient Cured patient

21. Increasing the availability of an efficacious drug is NOT the whole answer to controlling infectious diseases

22. Programmatic Effectiveness, Burkina Faso, 1994 7 steps for fully “effective” case management of malaria: • 1. Patient seeks help at clinic 21% • 2. Complete history taken 31% • 3. Physical exam done 69% • 4. Correct drug at correct dose recommended 81% • 5. Correct drug at correct dose bought by patient 91% • 6. Complete dose taken by patient 68% • 7. Efficacy of drug 85% Overall programmatic effectiveness = 3% Krause & Sauerborn, Annals Trop Paeds, 2000

23. Distribution challenges Drug resistance Wastage Drug toxicity Provider misuse Patient misuse What are some potential negative consequences of increasing the amount of drugs without simultaneously strengthening the health system? Illustrative

24. Things to Remember about Access to Antimicrobial Drugs and Drug Resistance 1. Drug resistance a constant threat as long as infectious diseases present and treated with antimicrobial drugs. 2. Rate of emergence of drug resistance faster in places where volume of drug use is greater and where drug use/quality are poor. Spread of drug resistance to other countries/regions will follow. 3.Increased access to antimicrobial drugs needs to be complemented by other programmatic interventions, e.g. monitoring drug resistance, drug use practices, and drug quality, use of tools for prevention of disease