Surveillance of Antimicrobial Resistance in India: from research capacity building to policy Child Health Research Project...
Background   <ul><li>3-5 million people die annually due to ARI worldwide. </li></ul><ul><li>Most of them are children fro...
INCREASING PREVALENCE OF ANTIMICROBIAL RESISTANT MICROBES <ul><li>Community-acquired infections </li></ul><ul><ul><li>Mult...
INCREASING PREVALENCE OF ANTIMICROBIAL RESISTANT MICROBES <ul><li>Hospital-acquired infections </li></ul><ul><ul><li>Methi...
Outline <ul><li>Invasive Bacterial Infections Surveillance (IBIS) in India </li></ul><ul><li>Other CHR activities on antim...
IndiaCLEN AMR Studies
IndiaCLEN IBIS Objectives <ul><li>To describe the epidemiology of invasive  S.pneumo- </li></ul><ul><li>niae  and  H. infl...
IndiaCLEN IBIS Study Team  1993-2002 <ul><li>Coordinators:  Dr.Kurien Thomas, Dr.M.K.Lalitha & </li></ul><ul><li>Dr. Mark ...
IndiaCLEN IBIS & CAMR  Study Sites Chennai Delhi Vellor e Lucknow Nagpur Thiruvananthapuram  Mumbai CChennaihennai Chennai
INCLUSION CRITERIA IBIS <ul><li>IBIS Phase I, 1993 - 1997 </li></ul><ul><li>All children fulfilling the WHO criteria for p...
Phase I & II  No.  recruited Phase I 1993 - 1998 5,798 Phase II 2000-Aug 01 Total 1,458 7,256* No. of  S. pneu- mo  isolat...
IBIS Phase II Update Meningitis & Lobar Pneumonia Cases 41 8 8 6 7 5 7 # QC tests 183 29 101 9 8 11 25 #  S. pneumo 72 26 ...
AMR  S.pneumoniae Time Trends
Newer AMR Studies <ul><li>Questions: </li></ul><ul><li>Do hospital AMR patterns reflect community AMR patterns? </li></ul>...
IBIS Phase II Update  (2000 – Aug. 2001) Nasopharyngeal swabs from children without respiratory illnesses presenting at OP...
Community AMR Study Group  2000-2001 <ul><li>Coordinators:   Dr.M.K.Lalitha, Dr.Kurien Thomas </li></ul><ul><li>& Dr. Mark...
CAMR Study Design <ul><li>2-year community-based study involving AMR surveillance through nasopharyngeal colonizing strain...
CAMR Update  (Aug. 28, 2000 – Sept. 31, 2001) Center Delhi Lucknow Nagpur Trivan- drum Vellore Total # tested 851  900  55...
Comparison of AMR Patterns: Invasive  S. pneumo  vs. IBIS NP & CAMR data   (Thomas K & IBIS, 2002) IBIS p = 0.32 CAMR p = ...
Comparison of AMR Patterns: Invasive  H. influenzae  vs. IBIS NP & CAMR data   (Thomas K & IBIS, 2002) IBIS p = 0.06 CAMR ...
Serotype/serogroup distributions Invasive  S. pneumo  vs. CAMR isolates Serotype/group  IBIS Invasive  CAMR Isolates (n = ...
Conclusions <ul><li>Pneumococcal resistance to penicillin is currently low in the Indian subcontinent. </li></ul><ul><li>E...
Policy <ul><li>We need to take steps to reduce the problem of emerging penicillin resistance. </li></ul><ul><ul><ul><li>De...
Other CHR Activities  Related to AMR
Expansion of AMR Surveillance <ul><li>IndiaCLEN surveillance of MDR-TB </li></ul><ul><li>IndiaCLEN IBIS is part of the Asi...
Clinical Studies <ul><li>PCN-resistant  S. pneumo  in severe pneumonia in children:  in vitro – in vivo  relationships (L....
Prescriber education and feedback <ul><li>Implementation of standard treatment guidelines for ARI through various methods ...
Economic Aspects of AMR <ul><li>WHO-Global Forum on HR collaboration: “Interventions against antimicrobial resistance: a r...
From Research Capacity Building to Policy
The case of IndiaCLEN IBIS <ul><li>Long and short courses on research design, measurement and evaluation </li></ul><ul><li...
The Case of IndiaCLEN IBIS <ul><li>Generation of important scientific information. </li></ul><ul><li>Strengthening of the ...
The case of IndiaCLEN IBIS <ul><li>Establishment and improvement of Institutional Review Board </li></ul><ul><li>Promotion...
The case of IndiaCLEN IBIS <ul><li>Regular discussions and contacts with Ministry of Health & state officials on results a...
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  • Acute Respiratory infections has become the the most important cause of morbidity and mortality after the control of diarrheal diseases in the developing world. 3- 5 million people die anually due to ARI and most of them are children from the developing world. Most common etiological agents in community aquired ARI in children are S.pneumonia and H.infuenzae in ~60% and Respiroaty syncitial virus causing the bulk of the other infections. These are preventable infections at the present time.
  • It is really been indeed a team effort by the investigators from different parts of India. Even though CMC has taken the leadership in microbiology and clinical coordination of the program. The success of the program has been the effort of all the members of the team.
  • The inclusion criteria has changed over the last 7 years. In the first phase from 1993 to 1997 we laid a wide net to cast all the possible infections due to Pneumococci and H.influenzae. We noted that overall we had less than 3% prospective yeild from blood while there was about 15% yeild from CSF . While providing similar AMR and serotype data. So in the second phase of the study from 1998 we have concentrated more on meningitis as the source of our isolates. While keeping lobar pneumonia and frank septicemias also in the inclusion criteria. All subjects who had routine isolations in the laboratory from normaly sterile body fluids were also included in the study if they full filled in the clinical inclusion criteria.
  • It is really been indeed a team effort by the investigators from different parts of India. Even though CMC has taken the leadership in microbiology and clinical coordination of the program. The success of the program has been the effort of all the members of the team.
  • We can draw a number of important conclusions from the study: Pneumococcal resistance is currently low in the range of 3% in India. Emerging penicillin resistance is a cuase for concern and needs attention. ( referring to 6% intermediate resistance seen in 1999). Both the bacteria show very high levels of resistance to currently recommended drugs in the ARI program. Sero types included in the commercially available 9 or 11 valant vaccine give coverage for both adults and children.
  • There is need to take steps to reduce emerging penicillin resistance in India. Development of antibiotic guidelines and hospital antibiotic policy some of the ways forward. We also need to control drug availability including that used in vetinary practice. There is need to systematically continue AMR surveillance so that we can evaluate the effect of interventional programs. And also provide information to guide rational antibiotic policy in the treatment of patient. There is no doubt that preventive strategies of reducing infections also reducing the antibiotic use and AMR development. The cost effectiveness of these vaccines in EPI program and high risk population will need to be evaluated.
  • We are part of global AMR surveillance net work ANSOP We have initiated regional collaboration at South Asia level with ICDDRB
  • It has been a very rewarding experience : Both in generating important data for the country But in developing the infrastructure for long term monitoring Lab strengthening, Reference centers in microbiology and data management.
  • Antimicro

    1. 1. Surveillance of Antimicrobial Resistance in India: from research capacity building to policy Child Health Research Project Coordination Meeting January 2002
    2. 2. Background <ul><li>3-5 million people die annually due to ARI worldwide. </li></ul><ul><li>Most of them are children from the developing world. </li></ul><ul><li>Most common etiological agents involved with ARI S.pneumoniae and H.influenzae (~60%). </li></ul>
    3. 3. INCREASING PREVALENCE OF ANTIMICROBIAL RESISTANT MICROBES <ul><li>Community-acquired infections </li></ul><ul><ul><li>Multidrug resistant pneumococci </li></ul></ul><ul><ul><li>Drug-resistant H. influenzae </li></ul></ul><ul><ul><li>FQ- and ESC-resistant Salmonella </li></ul></ul><ul><ul><li>Multidrug resistant Shigella </li></ul></ul><ul><ul><li>FQ-resistant gonococci </li></ul></ul><ul><ul><li>Multidrug-resistant M. tuberculosis </li></ul></ul><ul><ul><li>Drug-resistant malaria </li></ul></ul><ul><ul><li>Drug-resistant HIV </li></ul></ul>
    4. 4. INCREASING PREVALENCE OF ANTIMICROBIAL RESISTANT MICROBES <ul><li>Hospital-acquired infections </li></ul><ul><ul><li>Methicillin-resistant staphylococci </li></ul></ul><ul><ul><li>Vancomycin-resistant staphylococci </li></ul></ul><ul><ul><li>Vancomycin-resistant enterococci </li></ul></ul><ul><ul><li>ESC-resistant Gram-negative bacteria </li></ul></ul><ul><ul><li>Azole-resistant Candida </li></ul></ul>
    5. 5. Outline <ul><li>Invasive Bacterial Infections Surveillance (IBIS) in India </li></ul><ul><li>Other CHR activities on antimicrobial resistance surveillance (AMR) </li></ul><ul><li>Integrating capacity building and policy recommendations into CHR’s research portfolio </li></ul>
    6. 6. IndiaCLEN AMR Studies
    7. 7. IndiaCLEN IBIS Objectives <ul><li>To describe the epidemiology of invasive S.pneumo- </li></ul><ul><li>niae and H. influenzae disease in India, specifically: </li></ul><ul><ul><li>- Antimicrobial resistance patterns </li></ul></ul><ul><ul><li>- Serotype distribution </li></ul></ul><ul><li>To identify alternative strategies for long-term surveil- </li></ul><ul><li>lance: to compare hospital surveillance on invasive </li></ul><ul><li>isolates to nasopharyngeal swabs from: </li></ul><ul><ul><li>- Community-based surveillance data </li></ul></ul><ul><ul><li>- OPD pediatric cases with afebrile illnesses </li></ul></ul><ul><li>Bank of isolates for future genotyping (in relation to </li></ul><ul><li>future vaccine strategies) </li></ul>
    8. 8. IndiaCLEN IBIS Study Team 1993-2002 <ul><li>Coordinators: Dr.Kurien Thomas, Dr.M.K.Lalitha & </li></ul><ul><li>Dr. Mark Steinhoff </li></ul><ul><li>Co-investigators: </li></ul><ul><li>Dr.N.K.Arora, Dr.Bimal Das (New Delhi) </li></ul><ul><li>Dr.Shally Awasthi, Dr. Amita Jain (Lucknow) </li></ul><ul><li>Dr.Madhuri Kulkarni, Dr. Meenakshi Madhur (Mumbai) </li></ul><ul><li>Dr.Niswade, Dr.A.A.Pathak (Nagpur) </li></ul><ul><li>Dr.Thomas Cherian, Dr.L.Jeyaseelan (Vellore) </li></ul><ul><li>Dr.M.Narendranathan, Dr.Indira Kumari, Dr.Kavita Raja (Trivandrum) </li></ul>
    9. 9. IndiaCLEN IBIS & CAMR Study Sites Chennai Delhi Vellor e Lucknow Nagpur Thiruvananthapuram  Mumbai CChennaihennai Chennai
    10. 10. INCLUSION CRITERIA IBIS <ul><li>IBIS Phase I, 1993 - 1997 </li></ul><ul><li>All children fulfilling the WHO criteria for pneumonia </li></ul><ul><li>X-ray evidence of pneumonia </li></ul><ul><li>Children suspected of pyogenic meningitis and undergoing LP showing polymorph leukocytosis. </li></ul><ul><li>Fever in children with malnutrition </li></ul><ul><li>Short duration fever </li></ul><ul><li>Subjects with laboratory isolation of S. pneumo or H. infl. </li></ul><ul><li>IBIS Extension Phase II, 1998 - 2002 </li></ul><ul><li>All subjects with suspected pyogenic meningitis </li></ul><ul><li>X-ray evidence of lobar pneumonia </li></ul><ul><li>Subjects with suspected septicemia with hypotension </li></ul><ul><li>Subjects with laboratory isolation of S. pneumo or H.influenzae </li></ul>
    11. 11. Phase I & II No. recruited Phase I 1993 - 1998 5,798 Phase II 2000-Aug 01 Total 1,458 7,256* No. of S. pneu- mo isolates 307 183 490 * 58% < 2 y.o.; 92% children
    12. 12. IBIS Phase II Update Meningitis & Lobar Pneumonia Cases 41 8 8 6 7 5 7 # QC tests 183 29 101 9 8 11 25 # S. pneumo 72 26 26 1 16 2 1 # H. influenz. 308 3 152 38 9 0 106 # other fluids 1,117 355 168 102 199 196 97 # CSF samples 1,458 385 398 141 209 196 129 # re-cruited TOTAL Trivan-drum Vellore Nag-pur Mum-bai Luck-now Delhi
    13. 13. AMR S.pneumoniae Time Trends
    14. 14. Newer AMR Studies <ul><li>Questions: </li></ul><ul><li>Do hospital AMR patterns reflect community AMR patterns? </li></ul><ul><li>Are there alternative strategies for long-term AMR surveillance? </li></ul>Studies to address these questions: - Phase II IBIS: afebrile children in OPD - CAMR: school children
    15. 15. IBIS Phase II Update (2000 – Aug. 2001) Nasopharyngeal swabs from children without respiratory illnesses presenting at OPD 159 (20%) 32 45 0 5 48 29 # S. pneumo 106 (13.4%) 38 16 0 6 31 15 # H. influenz. 793 100 164 3 140 166 220 # of NP swabs TOTAL Trivan-drum Vellore Nag-pur Mum-bai Luck-now Delhi
    16. 16. Community AMR Study Group 2000-2001 <ul><li>Coordinators: Dr.M.K.Lalitha, Dr.Kurien Thomas </li></ul><ul><li>& Dr. Mark Steinhoff </li></ul><ul><li>Co-investigators: </li></ul><ul><li>Dr.N.K.Arora, Dr.Bimal Das (New Delhi) </li></ul><ul><li>Dr.Shally Awasthi, Dr. Amita Jain (Lucknow) </li></ul><ul><li>Dr. Dipty Jain, Dr Fule (Nagpur) </li></ul><ul><li>Dr.Indira Kumari, Dr Ramani Bai (Trivandrum) </li></ul>
    17. 17. CAMR Study Design <ul><li>2-year community-based study involving AMR surveillance through nasopharyngeal colonizing strains of S. pneumoniae and H. influenzae </li></ul><ul><li>A total of 1,200 children per center per year </li></ul><ul><li>Cross-sectional surveys carried out at intervals of 3 months </li></ul><ul><li>August 2000 – July 2002 </li></ul>
    18. 18. CAMR Update (Aug. 28, 2000 – Sept. 31, 2001) Center Delhi Lucknow Nagpur Trivan- drum Vellore Total # tested 851 900 550 472 1,220 3,993 # 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. 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 = 0.07 CAMR p = 0.001 IBIS p = 0.3 CAMR p = 0.005 IBIS p = 0.2 CAMR = 0.001 IBIS p = 0.9 CAMR p = 0.3 94 91 97 47 32 32 93 95 97 98 100 100 99 100 100
    20. 20. Comparison of AMR Patterns: Invasive H. influenzae vs. IBIS NP & CAMR data (Thomas K & IBIS, 2002) IBIS p = 0.06 CAMR p = 0.001 IBIS p = 0.3 CAMR p = 0.2 IBIS p = 0.001 CAMR p = 0.001 IBIS p = 0.04 CAMR p = 0.001 IBIS p = 1.0 72 87 93 45 46 57 53 87 86 80 65 36 100 100
    21. 21. Serotype/serogroup distributions Invasive 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. 22. Conclusions <ul><li>Pneumococcal resistance to penicillin is currently low in the Indian subcontinent. </li></ul><ul><li>Emerging penicillin resistance is a cause for concern and needs attention (0%-6% in last 7 Years) </li></ul><ul><li>Both H.influenzae and S.pneumoniae show high levels of resistance to co-trimoxazole which is the drug currently recommended by the ARI program. </li></ul><ul><li>Currently available 9- or 11- Valent vaccines provide ~70% coverage for the under 5 year age group </li></ul><ul><li>Nasopharyngeal swabs have potential as alternative strategy for AMR surveillance </li></ul>
    23. 23. Policy <ul><li>We need to take steps to reduce the problem of emerging penicillin resistance. </li></ul><ul><ul><ul><li>Development guidelines in use of antibiotics by the health profession. </li></ul></ul></ul><ul><ul><ul><li>Control of drug availability including veterinary use </li></ul></ul></ul><ul><li>There is need to systematically continue monitoring antimicrobial resistance. </li></ul><ul><ul><ul><li>to evaluate interventional policies </li></ul></ul></ul><ul><ul><ul><li>to guide rational treatment in individuals </li></ul></ul></ul><ul><li>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. </li></ul>
    24. 24. Other CHR Activities Related to AMR
    25. 25. Expansion of AMR Surveillance <ul><li>IndiaCLEN surveillance of MDR-TB </li></ul><ul><li>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 </li></ul><ul><li>IndiaCLEN IBIS has initiated regional collaboration in South Asia with ICDDR,B on antimicrobial resistance </li></ul>
    26. 26. Clinical Studies <ul><li>PCN-resistant S. pneumo in severe pneumonia in children: in vitro – in vivo relationships (L. America-WHO) </li></ul><ul><li>Using clinical treatment failures to monitor AMR (Pakistan-WHO) </li></ul><ul><li>Efficacy of various antibiotic options (drugs, duration) for pneumonia and bacterial meningitis (WHO, IndiaCLEN/ISCAP) </li></ul><ul><li>Improvement of diagnosis and treatment guidelines for ARI (WHO, INCLEN) </li></ul>
    27. 27. Prescriber education and feedback <ul><li>Implementation of standard treatment guidelines for ARI through various methods of dissemination (Vietnam, Indonesia-ARCH) </li></ul><ul><li>Education of private physicians, drugstore clerks, paramedics (Philippines, Nepal-ARCH) </li></ul>
    28. 28. Economic Aspects of AMR <ul><li>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 </li></ul><ul><li>Educational interventions that include cost considerations in decision-making and treatment (ARCH) </li></ul>
    29. 29. From Research Capacity Building to Policy
    30. 30. The case of IndiaCLEN IBIS <ul><li>Long and short courses on research design, measurement and evaluation </li></ul><ul><li>Long-term collaboration with U.S. investigators—technical (esp. laboratory techniques and QC), procurement of supplies, analysis and writing </li></ul><ul><li>“ Learning by doing”—research management, continuous quality improvement (epidemiology, laboratory, multicenter data management) </li></ul>
    31. 31. The Case of IndiaCLEN IBIS <ul><li>Generation of important scientific information. </li></ul><ul><li>Strengthening of the Network for research </li></ul><ul><li>Infrastructure development for continuing long-term AMR surveillance in the country. </li></ul><ul><ul><ul><li>Laboratory strengthening. </li></ul></ul></ul><ul><ul><ul><li>Reference center development </li></ul></ul></ul><ul><ul><ul><li>Data management and quality control </li></ul></ul></ul>
    32. 32. The case of IndiaCLEN IBIS <ul><li>Establishment and improvement of Institutional Review Board </li></ul><ul><li>Promotion of partnerships and linkages (USAID CHR partners, ANSORP, GAVI) </li></ul><ul><li>Discussions with Indian Council on Medical Research for sustained support for AMR surveillance </li></ul><ul><li>The birth of INCLEN ChildNET </li></ul>
    33. 33. The case of IndiaCLEN IBIS <ul><li>Regular discussions and contacts with Ministry of Health & state officials on results and implications of research findings </li></ul><ul><ul><li>Treatment guidelines for ARI </li></ul></ul><ul><ul><li>Disease surveillance in India </li></ul></ul><ul><ul><li>Vaccination strategies </li></ul></ul>

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