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Surveillance of Antimicrobial Resistance in India: from research capacity building to policy. Child Health Research Project Coordination Meeting January 2002. Background. 3-5 million people die annually due to ARI worldwide. Most of them are children from the developing world.

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surveillance of antimicrobial resistance in india from research capacity building to policy

Surveillance of Antimicrobial Resistance in India:from research capacity building to policy

Child Health Research Project Coordination Meeting

January 2002

slide2

Background

  • 3-5 million people die annually due to ARI worldwide.
  • Most of them are children from the developing world.
  • Most common etiological agents involved with ARI S.pneumoniae and H.influenzae (~60%).
increasing prevalence of antimicrobial resistant microbes
INCREASING PREVALENCE OF ANTIMICROBIAL RESISTANT MICROBES
  • Community-acquired infections
    • Multidrug resistant pneumococci
    • Drug-resistant H. influenzae
    • FQ- and ESC-resistant Salmonella
    • Multidrug resistant Shigella
    • FQ-resistant gonococci
    • Multidrug-resistant M. tuberculosis
    • Drug-resistant malaria
    • Drug-resistant HIV
increasing prevalence of antimicrobial resistant microbes1
INCREASING PREVALENCE OF ANTIMICROBIAL RESISTANT MICROBES
  • Hospital-acquired infections
    • Methicillin-resistant staphylococci
    • Vancomycin-resistant staphylococci
    • Vancomycin-resistant enterococci
    • ESC-resistant Gram-negative bacteria
    • Azole-resistant Candida
outline
Outline
  • Invasive Bacterial Infections Surveillance (IBIS) in India
  • Other CHR activities on antimicrobial resistance surveillance (AMR)
  • Integrating capacity building and policy recommendations into CHR’s research portfolio
indiaclen ibis objectives
IndiaCLEN IBIS Objectives
  • To describe the epidemiology of invasive S.pneumo-

niae and H. influenzae disease in India, specifically:

- Antimicrobial resistance patterns

    • - Serotype distribution
  • To identify alternative strategies for long-term surveil-

lance: to compare hospital surveillance on invasive

isolates to nasopharyngeal swabs from:

    • - Community-based surveillance data
    • - OPD pediatric cases with afebrile illnesses
  • Bank of isolates for future genotyping (in relation to

future vaccine strategies)

indiaclen ibis study team 1993 2002
IndiaCLEN IBIS Study Team 1993-2002

Coordinators: Dr.Kurien Thomas, Dr.M.K.Lalitha &

Dr. Mark Steinhoff

Co-investigators:

  • Dr.N.K.Arora, Dr.Bimal Das (New Delhi)
  • Dr.Shally Awasthi, Dr. Amita Jain (Lucknow)
  • Dr.Madhuri Kulkarni, Dr. Meenakshi Madhur (Mumbai)
  • Dr.Niswade, Dr.A.A.Pathak (Nagpur)
  • Dr.Thomas Cherian, Dr.L.Jeyaseelan (Vellore)
  • Dr.M.Narendranathan, Dr.Indira Kumari, Dr.Kavita Raja (Trivandrum)
indiaclen ibis camr study sites

Delhi

Lucknow

Nagpur

§

Mumbai

CChennaihennaiChennai

Vellor

e

Thiruvananthapuram

IndiaCLEN IBIS & CAMR Study Sites

Chennai

inclusion criteria ibis
INCLUSION CRITERIAIBIS

IBIS Phase I, 1993 - 1997

  • All children fulfilling the WHO criteria for pneumonia
  • X-ray evidence of pneumonia
  • Children suspected of pyogenic meningitis and undergoing LP showing polymorph leukocytosis.
  • Fever in children with malnutrition
  • Short duration fever
  • Subjects with laboratory isolation of S. pneumo or H. infl.

IBIS Extension Phase II, 1998 - 2002

  • All subjects with suspected pyogenic meningitis
  • X-ray evidence of lobar pneumonia
  • Subjects with suspected septicemia with hypotension
  • Subjects with laboratory isolation of S. pneumo or H.influenzae
phase i ii
Phase I & II

Phase I

1993 - 1998

Phase II

2000-Aug 01

Total

7,256*

5,798

1,458

No. recruited

No. of S. pneu-

mo isolates

307

183

490

* 58% < 2 y.o.; 92% children

newer amr studies
Newer AMR Studies

Questions:

  • Do hospital AMR patterns reflect community AMR patterns?
  • Are there alternative strategies for long-term AMR surveillance?

Studies to address these questions:

- Phase II IBIS: afebrile children in OPD

- CAMR: school children

slide15
IBIS Phase II Update (2000 – Aug. 2001)Nasopharyngeal swabs from children without respiratory illnesses presenting at OPD
community amr study group 2000 2001
Community AMR Study Group 2000-2001

Coordinators:Dr.M.K.Lalitha, Dr.Kurien Thomas

& Dr. Mark Steinhoff

Co-investigators:

  • Dr.N.K.Arora, Dr.Bimal Das (New Delhi)
  • Dr.Shally Awasthi, Dr. Amita Jain (Lucknow)
  • Dr. Dipty Jain, Dr Fule (Nagpur)
  • Dr.Indira Kumari, Dr Ramani Bai (Trivandrum)
camr study design
CAMR Study Design
  • 2-year community-based study involving AMR surveillance through nasopharyngeal colonizing strains of S. pneumoniae and H. influenzae
  • A total of 1,200 children per center per year
  • Cross-sectional surveys carried out at intervals of 3 months
  • August 2000 – July 2002
camr update aug 28 2000 sept 31 2001
CAMR Update (Aug. 28, 2000 – Sept. 31, 2001)

Delhi

Lucknow

Nagpur

Trivan-

drum

Vellore

Total

Center

851 900 550 472 1,220 3,993

# tested

# S. pneumo 211 157 117 83 352 920

# H. infl. 94 54 51 64 47 310

# + both 181 26 26 107 285 625

Colonization

rates (%) 57.1 31.6 35.3 53.8 56.1 48.3

comparison of amr patterns invasive s pneumo vs ibis np camr data thomas k ibis 2002
Comparison of AMR Patterns:Invasive S. pneumo vs. IBIS NP & CAMR data(Thomas K & IBIS, 2002)

IBIS p = 0.32

CAMR p = 0.08

IBIS p = 0.3

CAMR p = 0.005

IBIS p = 0.2

CAMR = 0.001

IBIS p = 0.9

CAMR p = 0.3

98 100 100

99 100 100

91 97

94

93 95 97

IBIS p = 0.07

CAMR p = 0.001

47

32 32

comparison of amr patterns invasive h influenzae vs ibis np camr data thomas k ibis 2002
Comparison of AMR Patterns:Invasive H. influenzae vs. IBIS NP & CAMR data(Thomas K & IBIS, 2002)

IBIS p = 1.0

IBIS p = 0.06

CAMR p = 0.001

IBIS p = 0.001

CAMR p = 0.001

IBIS p = 0.04

CAMR p = 0.001

100 100

93

87

87 86

IBIS p = 0.3

CAMR p = 0.2

80

72

65

57

53

45 46

36

serotype serogroup distributions invasive s pneumo vs camr isolates
Serotype/serogroup distributionsInvasive S. pneumo vs. CAMR isolates

Serotype/group IBIS Invasive CAMR Isolates

(n = 407) (n = 1,064)

1 24.6% -

6 10.8% 7.3%

19 6.3% 10.2%

7 5.2% -

5 4.2% -

14 3.7% -

4 2.9% 2.9%

18 2.9% -

3 1.5% 4.0%

conclusions
Conclusions
  • Pneumococcal resistance to penicillin is currently low in the Indian subcontinent.
  • Emerging penicillin resistance is a cause for concern and needs attention (0%-6% in last 7 Years)
  • Both H.influenzae and S.pneumoniae show high levels of resistance to co-trimoxazole which is the drug currently recommended by the ARI program.
  • Currently available 9- or 11- Valent vaccines provide ~70% coverage for the under 5 year age group
  • Nasopharyngeal swabs have potential as alternative strategy for AMR surveillance
policy
Policy
  • We need to take steps to reduce the problem of emerging penicillin resistance.
      • Development guidelines in use of antibiotics by the health profession.
      • Control of drug availability including veterinary use
  • There is need to systematically continue monitoring antimicrobial resistance.
      • to evaluate interventional policies
      • to guide rational treatment in individuals
  • The cost-effectiveness of introducing pneumo vaccine as part of EPI program in children and in the high risk population should be evaluated in India.
expansion of amr surveillance
Expansion of AMR Surveillance
  • IndiaCLEN surveillance of MDR-TB
  • IndiaCLEN IBIS is part of the Asian Network for Surveillance of Resistant Pathogens (ANSORP) study group with the work on S.pneumoniae and H.influenzae
  • IndiaCLEN IBIS has initiated regional collaboration in South Asia with ICDDR,B on antimicrobial resistance
clinical studies
Clinical Studies
  • PCN-resistant S. pneumo in severe pneumonia in children: in vitro – in vivo relationships (L. America-WHO)
  • Using clinical treatment failures to monitor AMR (Pakistan-WHO)
  • Efficacy of various antibiotic options (drugs, duration) for pneumonia and bacterial meningitis (WHO, IndiaCLEN/ISCAP)
  • Improvement of diagnosis and treatment guidelines for ARI (WHO, INCLEN)
prescriber education and feedback
Prescriber education and feedback
  • Implementation of standard treatment guidelines for ARI through various methods of dissemination (Vietnam, Indonesia-ARCH)
  • Education of private physicians, drugstore clerks, paramedics (Philippines, Nepal-ARCH)
economic aspects of amr
Economic Aspects of AMR
  • WHO-Global Forum on HR collaboration: “Interventions against antimicrobial resistance: a review of the literature and exploration of modelling cost-effectiveness”, RD Smith et al. 2002
  • Educational interventions that include cost considerations in decision-making and treatment (ARCH)
the case of indiaclen ibis
The case of IndiaCLEN IBIS
  • Long and short courses on research design, measurement and evaluation
  • Long-term collaboration with U.S. investigators—technical (esp. laboratory techniques and QC), procurement of supplies, analysis and writing
  • “Learning by doing”—research management, continuous quality improvement (epidemiology, laboratory, multicenter data management)
the case of indiaclen ibis1
The Case of IndiaCLEN IBIS
  • Generation of important scientific information.
  • Strengthening of the Network for research
  • Infrastructure development for continuing long-term AMR surveillance in the country.
      • Laboratory strengthening.
      • Reference center development
      • Data management and quality control
the case of indiaclen ibis2
The case of IndiaCLEN IBIS
  • Establishment and improvement of Institutional Review Board
  • Promotion of partnerships and linkages (USAID CHR partners, ANSORP, GAVI)
  • Discussions with Indian Council on Medical Research for sustained support for AMR surveillance
  • The birth of INCLEN ChildNET
the case of indiaclen ibis3
The case of IndiaCLEN IBIS
  • Regular discussions and contacts with Ministry of Health & state officials on results and implications of research findings
    • Treatment guidelines for ARI
    • Disease surveillance in India
    • Vaccination strategies