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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. 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

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  1. Surveillance of Antimicrobial Resistance in India:from research capacity building to policy Child Health Research Project Coordination Meeting January 2002

  2. 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%).

  3. 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

  4. 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

  5. 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

  6. IndiaCLEN AMR Studies

  7. 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)

  8. 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)

  9. Delhi Lucknow Nagpur § Mumbai CChennaihennaiChennai Vellor e Thiruvananthapuram IndiaCLEN IBIS & CAMR Study Sites Chennai

  10. 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

  11. 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

  12. IBIS Phase II UpdateMeningitis & Lobar Pneumonia Cases

  13. AMR S.pneumoniaeTime Trends

  14. 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

  15. IBIS Phase II Update (2000 – Aug. 2001)Nasopharyngeal swabs from children without respiratory illnesses presenting at OPD

  16. 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)

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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%

  22. 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

  23. 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.

  24. Other CHR Activities Related to AMR

  25. 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

  26. 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)

  27. 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)

  28. 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)

  29. From Research Capacity Building to Policy

  30. 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)

  31. 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

  32. 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

  33. 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

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