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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 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. • Most common etiological agents involved with ARI S.pneumoniae and H.influenzae (~60%).
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 MICROBES • Hospital-acquired infections • Methicillin-resistant staphylococci • Vancomycin-resistant staphylococci • Vancomycin-resistant enterococci • ESC-resistant Gram-negative bacteria • Azole-resistant Candida
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 • 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 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)
Delhi Lucknow Nagpur § Mumbai CChennaihennaiChennai Vellor e Thiruvananthapuram IndiaCLEN IBIS & CAMR Study Sites Chennai
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 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 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
IBIS Phase II Update (2000 – Aug. 2001)Nasopharyngeal swabs from children without respiratory illnesses presenting at OPD
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 • 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) 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) 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) 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 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 • 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 • 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 • 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 • 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 • 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 • 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 • 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 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 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 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