Controlling Drug Resistance

in Developing CountriesUSAID

Antimicrobial Resistance (AMR)Working Group*

ANE/E+E SOTA, October 2002*Includes: Neal Brandes, Tony Boni, Andrew Clements, Ruth Frischer, Marni Sommer, Cheri Vincent

Highlight the complexity of the drug resistance problem and its impact on controlling infectiousdiseases and USAID PHN programs.

Provide information on country-level approachesto control drug resistance and what assistance is available from USAID/W.

Objectives of Presentation

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

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

0

0.5

1

1.5

2

2.5

3

3.5

4

ARI HIV-AIDS DIARR.DISEASE

TB MALARIA

Millionsof deathsin 2000

Total infectious disease deaths: 14.4 million each year

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 Sectorand NGOs

Global Initiativese.g. RBM, GDF,

GFATM, Trachoma

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 problemBUT

Treatment failuredoesn’t always mean

drug resistance

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 sectorFills in where reach of public sector is limited

Producing/exporting antimicrobial drugs

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

Evidence that Treatment of Infectious Diseases Needs to be Improved

Sources: 2001 World Health Report and WHO reports

Total : 11,754,000

Outbreaks of Typhoid Fever (Salmonella typhi)

Year(s) ofOutbreak

Location Resistance Type

1989 Pakistan ACSSuTTm

1990-95 India ACSSuTTm

1990-95 Arabian Gulf ACSSuTTm

1990-93 Kuala Lumpur ACSSuTTm

1991 UK CSTTm1991 S. Africa ACSSuT1991-92 Egypt ACSSuTTm

1992-94 Vietnam ACSSuTTm

1993-94 Philippines CKSSuTTm1994 Bangladesh ACSSuTTm

1994-95 Pakistan ACSSuTTm1996-97 Tajikistan 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.

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 Malariafrom Cambodia (1960s)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 15April 11, 1996

Transmission of Multidrug-Resistant Mycobacterium

tuberculosis during a Long Airplane Flight

Drug Resistance: Everyone’s Problem Eventually

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

Cu

re R

ate

(%

)

$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)

0% 20% 40% 60% 80% 100%

ESTONIA 1999

CHINA (Henan Province)1996

RUSSIA (Ivanovo Oblast)1998

LATVIA 1998

RUSSIA (Tomsk Oblast) 1999

THAILAND 1997

SIERRA LEONE 1997 MDR-TB

Any drug resistanceother than MDRSusceptible

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

Consequences of not Addressing Contributing Factors: Cost of TB Drugs

Source of data: 2002 WHO Global Tuberculosis Control Report

Country(MDR rate innew cases)

Treatmentof:

NoMDR-TB

WithMDR-TB

Increased costdue to MDR-TB

NotifiedSS+ cases

$3.5million

$15.3million

$11.8 millionIndia(3.4%)

70% ofestimatedSS+ cases

$5.8million

$25.4million

$19.6 million

NotifiedSS+ cases

$0.3million

$1.8million

$1.5 millionRussia(6.0%)

70% ofestimatedSS+ cases

$0.6million

$4.2million

$3.6 million

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?

USAIDAMR

Activities

(http://www.who.int/emc/amr.html)

• 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?

Improved Procurement of TB Drugs: Example from Kazakhstan

Types of TB drugs procuredin 1998

Types of TB drugs procured after1999 tender with RPM assistance

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

• 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...

Accessibleto missionsthroughexisting GHagreements

USG Interagency Task Force on

Antimicrobial Resistance

Department ofDefense

Environmental Protection

AgencyAgency for Healthcare Research and Quality

Centers for Medicare and Medicaid Services

Health Resources and Services

Administration Department ofAgriculture

Department ofVeterans AffairsAgency for International

Development

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