Microbiology laboratory capacity building at a resource-poor setting in Bangladesh: Impact on child health policy

Transcription

1 Microbiology laboratory capacity building at a resource-poor setting in Bangladesh: Impact on child health policy Samir K Saha, Ph.D. Department of Microbiology Bangladesh

2 144 million people Bangladesh 7 th most populous country in the world Population density 1,002 persons/square kilometer (global mean 42) Per capita income - US$ 362 (?) ICDDR,B the state of the art International Centre Focused on diarrhoeal diseases Until recent past, other diseases were over shadowed, and.

3 Leading Killer of Children in Selection of Area of Work Bangladesh Other neonatal 7% Injury 4% Diarrhea 5% ARI+diarrhea 2% Birth asphyxia 12% ARI 21% Prematurity / LBW 7% Others? 7% Possible serious infection 31% Malnutrition 4%

4 Etiology of these deaths How much do we know about it? What do we need to explore this? Techniques and technologies Availability of technology Vs prevalence of diseases

5 Childhood mortality

6 Countries with technologies

7 Why are the microbiology laboratories resource poor? Resource poor labs may not be financially poor Annual budget Vs expenditure of public institutes How much do we know about these labs and what is the basis of our knowledge? ICDDR,B, AKU, MRC, etc. Do these state of the art institutes represent the laboratories of resource poor countries?

8 Budget and priority identification New system comes with lot of fanfare Policy makers get convinced Reference labs Vs Service labs Few examples Platelet separator Where blood bank can not ensure to provide safe blood Lying idle Automated blood culture machine Where labs still use human blood No budget to buy the culture bottles Laboratories bought automated machines never used.

9 Microbiology laboratories in Bangladesh Non existent at district level hospitals Leading Medical colleges While working for capacity building of microbiology laboratories in 6 large hospitals Staffs are highly qualified Teaching S. pneumoniae and H. influenzae for decades Log books showed almost no isolation of Hib or Pneumo Minimum or no resources and thus less or no specimen; or vice versa Least communication between clinicians and microbiologists

10 Poor microbiology lab: impact on policy decisions This if the 15 th year of Hib and 5 th year of Pneumo vaccine introduction in USA These vaccines are not available in the countries where 90% of the diseases occur GAVI fund could not be utilized by most of the eligible countries What is the main obstacle? Disease burden data We have medical colleges, hospitals, great academicians but no data! Non functional laboratories Why?

11 Hospital dynamics and laboratory capacity building Hospital management is the most complicated dynamics due to multi-disciplinary groups Administration, finance, clinicians, nurses, laboratory personal, other staffs Shishu is no exception from this How can we work within these complexities? Involved leading clinician with the lab related work Related that with their work

12 We The need Vicious to change Cycle it to of a Developing Virtuous Limited Resources Countries Cycle Lack of evidence Improper or inadequate use Adequate Limited resources Generation of evidence Optimum and rational use

13 Capacity building occurs when all 3 work collaboratively Policy maker/ Admin/Finance manager Researcher/ Lab personal Pediatrician/ Clinician

14 Largest Pediatric Hospital 470 beds in different disciplines 53% of the beds are free for poor Large out patient department - ~150,000 patients/year

15 Shishu Microbiology in 1989 Photo frame size space in the veranda of clinical pathology Arranged a bench, pressure cooker, incubator and few glass plates My teachers on those days

16 Why to present this at IUB? We want to see more functional microbiology laboratory Good laboratory practice Increased capacity Impact on child health policy

17 How things started rolling? Proactive laboratory Communicating results Volunteering to do additional diagnostic work Work was based on the need of the clinicians Indigenous Lysis direct-plating/centrifugation method Rapid and quantitative blood culture Rapid antimicrobial susceptibility test (RAST) Influence on clinical colleagues and administration

18 Lysis-direct plating/centrifugation method Mix Growth of Bacteria at hours Saha et al. 1991; Trans Royal Soc Trop Med Hyg Saha et al. 2001; J Clin Microbiol

19 Advantage of working in a pediatric hospital m 13-24m 25-36m 37-48m 5-9y 10-12y Saha et al Pediatr Infect Dis J, 2000; Saha et al. J Clin Microbiol, % <=67h <=54h 90% <=47h 80% Magnitude of 70% bacteremia is 60% indirectly 50% proportional to <=30h age. 40% 30% Implications in deciding blood 20% volume 10% 0% RAST; reduced turn around time

20 Rapid Diagnosis of Pneumococcal Meningitis Implications for Treatment and Measuring Disease Burden Samir K. Saha, PhD,* Gary L. Darmstadt, MD, Noboru Yamanaka, MD, PhD, Dewan S. Billal, MSc,* Tania Nasreen, MSc,* Maksuda Islam, BA,* and Davidson H. Ham MD Base line work impact on INVASIVE HAEMOPHILUS INFLUENZAE TYPE B DISEASES IN BANGLADESH, WITH INCREASED RESISTANCE TO ANTIBIOTICS SAMIR K. SAHA, PHD, ABDULLAH H. BAQUI,MBBS, MPH, DRPH, GARY L DARMSTADT, MD,MS,M. RUHULAMIN, MBBS, FCPS, MOHAMMED HANIF, MBBS, FRCP, FCPS, SHAMS policy Pneumonia, septicaemia and EL ARIFEEN, MBBS, MPH, KAZUNORI OISHI, MD,MATHURAM SANTOSHAM, MD,MPH, TSUYOSHI NAGATAKE, MD, PHD, AND ROBERT E. BLACK, MD,MPHO Septicemic Neonates Without Lumbar Puncture: What are we Missing? by Md. Mahbubul Hoque,a A.S.M. Nawshad Uddin Ahmed,a,d M.A.K. Azad Chowdhury,a Gary L. Darmstadt,b,c and Samir K. Sahaa,b Comparison of Antibiotic Resistance and Serotype Composition of Carriage and Invasive implications Pneumococci among treatment Bangladeshi Children: Implications for Treatment Policy and Vaccine Formulation Rapid Identification and Antibiotic Susceptibility Testing of Salmonella enterica Serovar Typhi Isolated from Blood: Implications for Therapy Samir K. Saha,1,2* Abdullah H. Baqui,2,3 Gary L. Darmstadt,2,4 M. Ruhulamin,1 Mohammed Hanif,1 Shams El Arifeen,3 Mathuram Santosham,2 Kazunori Oishi,5 Tsuyoshi Nagatake,5 and Robert E. Black2 SAMIR K. SAHA,1,2* GARY L. DARMSTADT,3,4 ABDULLAH H. BAQUI,3 M. HANIF,1,2 M. RUHULAMIN,1,2 MATHURAM SANTOSHAM,3 T. NAGATAKE,5 AND ROBERT E. BLACK3 Serotypes of Streptococcus pneumoniae Causing Invasive Childhood Infections in Bangladesh, 1992 to 1995 SAMIR K. SAHA,1* N. RIKITOMI,2 D. BISWAS,1 K. WATANABE,2 M. RUHULAMIN,3 K. AHMED,2 M. HANIF,3 K. MATSUMOTO,2 R. B. SACK,4 AND T. NAGATAKE2 Antimicrobial Resistance and Serot Streptococcus pneumoniae Strains C Infections in Bangladesh, 1993 to 19 SAMIR K. SAHA,1* N. RIKITOMI,2 M. RUHU MAKSUDA ISLAM,1 K. WATANABE,2 K. AH SACK,4 AND T. NAGATAKE1 Effect of topical treatment with skin barrier-enhancing emollients on nosocomial infections in preterm infants in Bangladesh: a randomised controlled trial Gary L Darmstadt, Samir K Saha, A S M Nawshad Uddin Ahmed, M A K Azad Chowdhury, Paul A Law, Saifuddin Ahmed, Muhammad Asif Alam, Robert E Black, Mathuram Santosham meningitis Always focused on public health issues Drug resistance Serotype distribution of S. pneumoniae and H. influenzae Implications on vaccine formulation Age group distribution implication on vaccination policy

21 % of Multidrug resistant strains Surveillance on drug resistance Progressive 80 increase in Hospital relative 71 Community 70 resistance to 56 Ciprofloxacin Delay in clinical response Higher dose Treatment failure 13 Recurrence Typhoid perspective No. of cases Decrease in drug 62 resistance Remarkable difference between hospital and community isolates. 22 Ideal practice in Bangladesh and. Hospital Vs community Saha et al. J Antimicrobiol Chemotherapy, 1995, 1997.

22 VNTR Pattern of Ciprofloxacin Resistant S. Typhi Compared to Sensitive Strains 600 bp 500 bp 400 bp 300 bp 200 bp 100 bp Lane 1: 100 bp marker; Lane 2-4: Ciprofloxacin resistant strains (MIC 512µg/ml), Lane 5-7, Ciprofloxacin sensitive strains, MIC 0.032, 0.064, 0.25 µg/ml respectively. Identical clone Encountering many other strains Possible reason Saha et al. J Clin Microbiol 2006 Misleading definition of Ciprofloxacin resistance >2.0 ug/ml

23 Age group distribution of Typhoid cases impact on impact on typhoid vaccination policy Existing vaccine will not Conjugate be effective vaccine 23% needed of for cases this group 97% coverage 7 1 1st 2nd 3rd 4th 5th 6th 7th 8th 9th 10th 11th 12th >12th 0-6m 0-12m 0-24m 0-36m 0-48m 0-60m 0-9y 0-19y All age With effective 12 conjugate vaccine Recommended New age recommendation of vaccination for vaccination Saha et al Pediatric Infectious Diseases Journal, 2000

24 Progressive increase in MDR of Hib: impact on outcome of meningitis 60 57% MDR Sensitive 50 % of resistant strains % 31% 31% 12% 24% Cured Disability Death Saha et al. Journal of Pediatrics 2005

25 Outcome of Hib meningitis cases in relation to drug resistance (n=425) % of resistant strains Progressive increase of MDR MDR is directly related to disability and dealth Most deaths occur before antibiotic can do anything % MDR Sensitive 36% 31% 31% 24% 12% Cured Disability Death Saha et al. J Pediatrics, 2005

26 Application of molecular techniques: definitive therapy in culture negative cases MDR Plasmid genome of H. influenzae Used as a tool to see phylogenetic evolution of MDR strains How are we using that? Detecting the genome in culture negative CSF specimens Contributing in treatment policy

27 70 Application of molecular techniques: definitive therapy in culture negative cases 60 ICT, LP +ve, 43% Latex, 33 Latex, 29 LP 30 LP -ve, 57% Bex Culture, 19 Culture, 23 0 H. influenzae (52) S. pneumoniae (62)

28 Serotype and drug resistance of S. pneumoniae: implications in treatment of vaccination policy Low penicillin resistance High resistance to Cotromoxazole Blood CSF Pen Cotrim Chloram Serotypes Diverse and different from developed part of the world Low coverage by existing vaccine type 25-30% Our serotypes are considered for inclusion in upcoming vaccine formulation Saha et al 1991, 1997, 1999, 2000

29 Validation of BinaxNow to diagnose pneumococcal meningitis BinaxNow - developed to detect Pneumococcal antigen in urine Not useful We used the largest series of meningitis cases Gold standard PCR 100% sensitive and specific Implications in measuring disease burden Treatment policy ICT, 10 Latex, 29 Culture, 23 S. pneumoniae (62) Saha et al 2005 Pediatric Infectious Diseases POSITIVE NEGATIVE

30 70 Limitation of Pneumococcal antigen detection 60 ICT, A 18B 18C NC B 5 12F 12A 15B 45 NC Latex, CPS Culture, 23 S. pneumoniae (62) Importance to public health and donors New serotypes More output within short time Cost effective

31 Most significant impact of our work in country policy decision BBC film on Hib World Bank, WHO, UNICEF and our Government prepared MYP Applying to GAVI and introduce Hib vaccine in EPI by 2008 It all based on the data generated from Shishu microbiology

32 We The need Vicious to change Cycle it to of a Developing Virtuous Limited Resources Countries Cycle Lack of evidence Improper or inadequate use Adequate Limited resources Generation of evidence Optimum and rational use

33 The team is getting bigger

34 Our mentors Prof. T. Nagatake, Nagasaki University, Japan Prof. Mathuram Santosham, Johns Hopkins University Prof. Robert Black, Johns Hopkins University

35 Largest Pediatric Hospital 387 beds in different disciplines 53% of the beds are free for poor Large out patient department - ~150,000 patients/year Adequate Laboratory Facilities Research (Public Health) Clinical trial Vaccine trial Surveillance for invasive diseases Collaborating with JHU Nagasaki University Oxford University WHO ICDDR,B Save the Children, USA GAVI s PneumoADIP GlaxoSmithKline

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