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EPIDEMIOLOGICAL INVESTIGATION OF S.PNEUMONIAE INVASIVE INFECTIONS IN ARGENTINIAN CHILDREN

EPIDEMIOLOGICAL INVESTIGATION OF S.PNEUMONIAE INVASIVE INFECTIONS IN ARGENTINIAN CHILDREN. PARTICIPANT INSTITUTIONS HOSPITAL CITY. SOR LUDOVICA CHILDREN HOSPITAL LA PLATA P. GARRAHAM CHILDREN HOSPITAL B. AIRES

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EPIDEMIOLOGICAL INVESTIGATION OF S.PNEUMONIAE INVASIVE INFECTIONS IN ARGENTINIAN CHILDREN

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  1. EPIDEMIOLOGICAL INVESTIGATION OF S.PNEUMONIAE INVASIVE INFECTIONS IN ARGENTINIAN CHILDREN PARTICIPANT INSTITUTIONS HOSPITAL CITY SOR LUDOVICA CHILDREN HOSPITAL LA PLATA P. GARRAHAM CHILDREN HOSPITAL B. AIRES R. GUTIERREZ CHILDREN HOSPITAL B. AIRES P. ELIZALDRE CHILDREN HOSPITAL B. AIRES NOTTI CHILDREN HOSPITAL MENDOZA S. JUSTO CHILDREN HOSPITAL SAN JUSTO (Bs.As.) INFANT CHILDREN HOSPITAL CORDOBA R. GUTIERREZ CHILDREN HOSPITAL SANTA FE MUNICIPAL ITURRASPE HOSPITAL SANTA FE NIÑOS JESUS CHILDREN HOSPITAL TUCUMAN MUNICIPAL CHILDREN HOSPITAL CORDOBA CHILDREN HOSPITAL :”VILELA” ROSARIO (S.FE) REGIONAL HOSPITAL NEUQUÉN C. DURAND MUNICIPAL HOSPITAL BUENOS AIRES REGIONAL HOSPITAL POSADAS (MISIONES)

  2. EPIDEMIOLOGICAL INVESTIGATION OF S.PNEUMONIAE INVASIVE INFECTIONS IN ARGENTINIAN CHILDREN STREPTOCOCCUS PNEUMONIAE WORKING GROUP ALTSCHULER M. YUDOWSKY S. FAVRE R. GONZALEZ AYALA S. TREGNAGHI M. DALAMON R. FERNANDEZ C. MAYORAL C. GRENON S. BOLOGNA R. BELTRAMINO J.C. RUBEGLIO E. CALAFELL M.C.L. de BAKIR J. GAITE J.P. de FERNANDEZ G.N. TREJO A.V. de GALANTERNIK L. CUZA N. FERRERO F. CARBAJAL L. ALARCON N. SILBERBERG R. APRA E. NORIEGA M. BALBI de AGUIRRE L. DIAZ N. MECCIA A. KREMER C. LOGARZO D.PEREZ C.

  3. EPIDEMIOLOGICAL INVESTIGACION OF S.PNEUMONIAE INVASIVE INFECTIONS IN ARGENTINIAN CHILDREN • RUVINSKY R., ROSSI A., REGUEIRA M., CORSO A., PACE J., • GENTILE A. AND S. PNEUMONIAE WORKING GROUP • MINISTERIO DE SALUD PUBLICA DE LA NACION. ACUTE • RESPIRATORY INFECTION (ARI) PROGRAM FOR ARGENTINA • INSTITUTO NACIONAL DE MICROBIOLOGIA Dr. C. MALBRAN,, • BACTERIOLOGY DEPARTMENT, Bs. As., ARGENTINA • HOSP. DE NIÑOS R. GUTIERREZ, EPIDEMIOLOGY UNIT. • PAHO (SIREVA GROUP) • LCDC, OTAWA, CANADA - • NAT. CENTRE FOR STREPT, ALBERTA,CANADA • 1996

  4. STREPTOCOCCUS PNEUMONIAE CONJUGATE VACCINES 1 - LEDERLE PRAXIS: 7 OR 9 - VALENT, CONJUGATED WITH CRM 197 USA AND FINLAND: FASE I AND II - GAMBIA: FASE III 2 - M.S.D.: 3 - 4 VALENT, CONJUGATED WITH OMP OF N.MENINGITIDIS. SEROGROUP B (TRANSPORT PROTEIN) 3 - MERIEUX INSTITUTE: 4-VALENT, CONJUGATED WITH TETANIC AND DIFTERIC TOXOID 4 - RIJS INSTITUT (HOLLAND): 6 OR 8 - VALENT, CONJUGATED WITH TETANIC TOXOID 5 - GENETICALLY INACTIVATED PNEUMOLYSIN (CLINICAL STUDIES NOT DEVELOPED)

  5. STREPTOCOCCUS PNEUMONIAE VACCINE 23-VALENT (#) A.C.I.P. RECOMENDATIONS • FUNCTIONAL OR ANATOMIC ASPLENIA • SICKLE -CELL DISEASE • NEPHROTIC SYNDROME • CHRONIC RENAL FAILLURE • CONDITIONS ASSOCIATED WITH IMMUNODEPRESSION • HODGKIN’S DISEASE (*) • ORGAN TRANSPLANTATION • CYTORREDUCTION THERAPY • C.S.F. LEAKS • H.I.V. INFECTION • (*) Two weeks before the initiation of chemotherapy or irradiation • (#) children more than 2 years of age .

  6. STREPTOCOCCUS PNEUMONIAE: INVASIVE INFECCIONS IN CHILDREN IN ARGENTINA: PENICILLIN RESISTANCE FACTORS TOTAL(n) R(%) p RR (CI 95%) TYPE 14 149 59.8 < 0.0001 6.66 (4.56 - 9.73) OTHER TYPES 310 9.0 PROCEDENCE METROPOL.(Bs.As.) 224 29.5 < 0.0001 1.43 (1.05 - 1.94) OTHER CITIES 281 20.6 NORT OF COUNTRY 23/281 26.1 CENTRE AREA 216/281 21.3 SOUTH 42/281 14.3 < 2 YEARS OLD 288 39.5 < 0.0009 1.99 (1.31 - 3.020) > 2 YEARS OLD 155 14.8 PNEUMONIA 273 27.5 < 0.008 2 (1.19 - 3.38) MENINGITIS 102 13.7 ( Rep. Argent. 1996 )

  7. RECOMMENDED CHEMOPROPHYLAXIS FOR HIGH RISK CONTACTS AND INDEX CASES OF INVASIVE MENINGOCOCCAL DISEASE ANTIBIOTICDOSE DURATION EFFICACY (%) RIFAMPIN * < 1 MONTH 5mg/Kg. b / d2d72 - 90 > 1 MONTH 10mg/Kg. b / d2d (Maximum 600mg/Kg.) or20mg / Kg./d (Maximum 600 mg/Kg e/24 hs 4 d CEFTRIAXONE < 12 Y 125 mg. IM Single dose 97 > 12 Y 250 mg. IM Single dose * Not for use in pregnant women American Academy of Pediatrics - Comm. of Infectious Diseases Pediatrics 1996, 97(3): 404-11

  8. RECOMMENDATIONS FOR ADMINISTRATION OF MENINGOCOCCAL VACCINE (A, C, Y, W 135) • FUNCTIONAL or ANATOMIC ASPLENIA • TERMINAL COMPLEMENT DEFFICIENCY (C5 - C8) • PROPERDINA DEFFICIENCY • TRAVELING or RESIDING IN COUNTRY WITH HYPEREN- • DEMIC OR EPIDEMIC MENINGOCCAL DISEASE • (CAUSED by A VACCINE PREVENIBLE SEROGROUP) * • CHILDREN ASSOCIATED WITH AN OUTBREAK or • CLUSTER OF CASES, IF ISOLATE OF INDEX CASE • BELONGS TO SEROGROUP A, C, Y or W-135 • *Recomended also for infants older than 3 months of age trave- • lling to an area with hyperendemic or epidemic serogroup A

  9. RECOMMENDED CHEMOPROPHYLAXIS FOR HIGH RISK CONTACTS AND INDEX CASES OF INVASIVE MENINGOCOCCAL DISEASE THE CASE INDEX SHOULD RECEIVE CHEMOPROPHYLAXIS BEFORE DISCHARGE (UNLESS TREATED WITH CEFTRIAXONE) CHEMOPROPHYLAXIS SHOULD BE GIVEN WITHIN 24 hs. OF CASE IDENTIFICATION (IDEALLY) CHEMOPROPHYLAXIS IS OF LESS VALUE IF MORE THAN 2 WEEKS HAVE LAPSED AFTER THE CONTACT OUTSIDE OF RIFAMPIN AND CEFTRIAXONE, SULFISOXASOLE (1) AND CIPROFLOXACIN (2) ARE RECOMMENDED IN SPECIAL CASES RIFAMPIN IS EFFECTIVE IN ERRADICATING NASOPHARING. CARRIAGE (1) If the organism is known to be susceptible (< 1 y of age: 500 mg/d: 2 d., 1 to 12 y.: 500 mg. e/12 hs. for 2 d., > 12 y.: 1 gm e/12 hs, for 2 d. (2) In > 18 y of age: 500 mg. orally: single dose (efficacy: 90-95%)

  10. CHEMOPROPHYLAXIS RECOMMENDED FOR CONTACTS OF INDEX CASES OF INVASIVE MENINGOCOCCAL DISEASE • HIGH RISK • CHILD CARE SCHOOL CONTACT IN PREVIOUS.7 DAYS • DIRECT EXPOSURE TO INDEX PATIENT’S SECRETIONS • HOUSEHOLD CONTACT • MOUTH TO MOUTH RESUSCITATION, UNPROTECTED • CONTACT DURING ENDOTR. INTUBAT.(7 DAYS BEFORE) • FREQUENTLY SLEEPS OR EATS IN SAME DWELLING • IN OUTBREAK: OTHER THAN HIGH RISK ONLY AFTER • CONSULTATION WITH LOCAL HEALTH AUTHORITIES • R.O.R. Durand Hosp. 1996

  11. CHEMOPROPHYLAXIS NOT RECOMMENDED FOR CONTACTS OF INDEX CASES OF INVASIVE MENINGOCOCCAL DISEASE • LOW RISK: • CASUAL CONTACT: NOT DIRECT EXPOSITION TO • INDEX PATIENT’S ORAL SECRETIONS (SCHOOLMATE) • INDIRECT CONTACT: CONTACT ONLY WITH HIGH • RISK CONTACT • HEALTH WORKING GROUP WITHOUT DIRECT • EXPOSITION TO PATIENT’S ORAL SECRETIONS • R.O.R. Durand Hosp. 1996

  12. CHEMOPROPHYLAXIS RECOMMENDED FOR CONTACT OF INDEX CASES OF INVASIVE H. INFLUENZAE TYPE b DISEASE • RIFAMPIN: • ALL HOUSEHOLD CONTACTS, IRRESPECTIVE • OF AGE, IN THOSE HOUSEHOLD WHIT AT LEAST ONE • CONTACT YOUNGER THAN 48 MONTH • DAY CARE: WHEN CHILDREN • HOUSEHOLD CONTACTS: • RIFAMPIN: WHEN THERE ARE AT LESS ONE CONTACT • WITHOUT Hi b CONJUGATE VACCINE LESS THAN 48 • MONTH OF AGE • R.O.R. Durand Hosp. 1996

  13. RIFAMPIN PROPHYLAXIS RECOMMENDED FOR CONTACT OF INDEX CASES OF INVASIVE H. INFLUENZAE TYPE b DISEASE • DAY CARE and NURSERY SCHOOL: • CHILDREN < THAN 2 Y. IN WICH CONTACT IS > 25 HS PER WEEK • WHEN 2 or MORE CASES HAVE OCURRED WITHIN 60 DAYS, RIFAMPIN • TO ALL ATTENDEES AND PERSONNEL IS RECOMMENDED • CHILDREN WITHOUT COMPLETE VACCINE SHOULD BE • RECEIVE CONJUGATE VACCINE • Dose:: 20 mg./Kg., e / 24 hs., maximum: 600 mg. e / d. (4 days) • < 1 month of age: 10 mg./ Kg., e / d. • (pregnant women: ceftriaxone prophylaxis: 250 mg. single dose) • Rep. of the Commit.on Infect. Dis, Amer. Acad. Ped. 1994

  14. RIFAMPIN PROPHYLAXIS RECOMMENDED FOR CONTACT OF INDEX CASES OF INVASIVE H. INFLUENZAE TYPE b DISEASE • HOUSEHOLD CONTACTS: • IRRESPECTIVE OF AGE, WITH AT LEAST ONE CONTACT YOUNGER • THAN 48 MONTHS WITHOUT COMPLETE CONJUGATE VACCINE • (Erradicates H.i.b from the pharynx in 95% of the carriers) • CONTACT YOUNGER THAN 12 MONTH VACCINATED, BUT WITHOUT • THE ADDITIONAL DOSE) • IRRESPECTIVE OF AGE, IMMUNOCOMPROMISSED CHILDREN WITH • or WITHOUT COMPLETE CONJUGATE VACCINE • “The index case treated with ceftriaxone don’t need Rifampin • prophylaxis” • Report of the Committee on Infectious Diseases, • American Academy of Pediatrics, 23* Ed., 1994

  15. INVASIVE MENINGOCCAL DISEASE: VACCINES IN DEVELOPPMENT • CROSS-REACTIVITY BETWEEN A MONOCLONAL Ab. TO THE GROUP B • POLYSACCHARIDE VS. FETAL TISSUE GLYCOPROTEINS (Finne) • N-PROPIONYLATED GROUP B POLYS. CONJUGATED TO • THE TETANUS-TOXOID, INDUCED B.A. IN MICE (Jennings) • POLYS. FROM E.COLI K 92 CONJUGATED TO A CARRIER • PROTEIN TO ELICIT Ab VS. GROUP B POLYSACCHARIDE • (de Moraes - Perkins, 1992) • NON-CAPSULAR Ags:OMP’s of SEROTYPES 6, 2, 2a, 2b INDUCED • IMMUNOGENICITY IN HUMANS • 2b and 15 complexed with A, C, Y and W-135 POLYS. PRODUCED • SEROTYPE-SPECIFIC Ab. IN HUMAN VOLUNTEERS • Riedo F et al. Pediatr. Infect. Dis. 1995,14:643-57 • R.O.R. Durand Hosp. 1996

  16. INVASIVE MENINGOCCAL DISEASE: VACCINES IN DEVELOPPMENT • MENINGOCOCCAL B:15:P1.15 OMP VACCINE COMPLEXED • WITH GROUP C POLYSACCHARIDE (Iquique, Chile: 51% efficacy) • B:4:P1.15 OMP VACCINE and HIGH m.w. PROTEIN COMPLEXED • WITH THE GROUP C POLYS. IN CUBA: 83% EFFICACY IN • STUDENTS 10-14 YEARS OF AGE • CASE-CONTROL STUDY (S.Paulo): > 48 m. to 6 Y.: 74% efficacy • b:15:p1.7,16 N.meningitidis strain (Norwegians): low efficacy • Riedo F et al. Pediatr. Infect. Dis. 1995,14:643-57 • R.O.R. Durand Hosp. 1996

  17. RAPID DISAPPEARANCE OF Hi TYPE b MENINGITIS AFTER ROUTINE CHILDHOOD IMMUNIZATION WITH CONJUGATE VACCINES • HI b CONJUGATE VACCINES ADMINISTERED IN HELSINKI • 1986-7 PRP-D TO 50% OF CHILDREN • 1988-9 PRP-D (50%) and CRM197 (50%) • 1990 PRP-T ROUTINELY ADMINISTERED TO ALL INFANTS • THE NUMBER OF CASES OF Hi b MENINGITIS IN CHILDREN AGED 0-4 Y • DECREASED FROM 30 IN 1986 TO 0 IN 1991 • CONCLUSION: • PEAK INCIDENCE IN CHILDREN YOUNGER THAN 4 YEARS OF AGE: • 43/100.000 IN 1970 • 0 IN 1991 • Source: Peltola H et al. Lancet 1992,340:592-4

  18. 23 - VALENT PNEUMOCCAL VACCINE A.C.I.P. RECOMMENDATIONS • FUNCTIONAL OR ANATOMIC ASPLENIA • NEPHROTIC SYNDROME or C.R.F. • SICKLE CELL DISDEASE • IMMUNOSUPPRESSION CONDITIONS • LYMPHOMAS • ORGAN TRANSPLANTATION • CYTOREDUCTION THERAPY • CSF LEAKS • AIDS • R.O.R. Durand Hosp. 1996

  19. EPIDEMIOLOGY OF INVASIVE S.PNEUMONIAE IN ARGENTINIAN CHILDREN • HOSPITAL LABORATORIES • QUALITY CONTROL OF CULTURE MEDIA • CULTURE AND ISOLATION OF S.PNEUMONIAE • ISOLATES ARE SENT TO THE REFERENCE LAB. (INM) • EPIDEMIOLOGICAL AND LAB. INFORMATION ARE • SENT TO CLINICAL AND LAB. COORDINATORS • REFERENCE LABORATORY • SEROTYPING • SENSITIVITY TO ANTIBIOTICS • DATA ENTRY TO EPIINFO AND WHONET PROGRAMS • INTERNATIONAL REFERENCE LAB. (QUALITY CONTROLS)

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