EPIDEMIOLOGICAL INVESTIGATION OF S.PNEUMONIAE INVASIVE INFECTIONS IN ARGENTINIAN CHILDREN

PARTICIPANT INSTITUTIONS HOSPITAL CITY

SOR LUDOVICA CHILDREN HOSPITAL LA PLATAP. GARRAHAM CHILDREN HOSPITAL B. AIRESR. GUTIERREZ CHILDREN HOSPITAL B. AIRESP. ELIZALDRE CHILDREN HOSPITAL B. AIRESNOTTI CHILDREN HOSPITAL MENDOZAS. JUSTO CHILDREN HOSPITAL SAN JUSTO (Bs.As.)INFANT CHILDREN HOSPITAL CORDOBAR. GUTIERREZ CHILDREN HOSPITAL SANTA FEMUNICIPAL ITURRASPE HOSPITAL SANTA FENIÑOS JESUS CHILDREN HOSPITAL TUCUMANMUNICIPAL CHILDREN HOSPITAL CORDOBACHILDREN HOSPITAL :”VILELA” ROSARIO (S.FE)REGIONAL HOSPITAL NEUQUÉNC. DURAND MUNICIPAL HOSPITAL BUENOS AIRES

REGIONAL HOSPITAL POSADAS (MISIONES)

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. deBAKIR J. GAITE J.P. deFERNANDEZ G.N. TREJO A.V. deGALANTERNIK 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.

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

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)

.

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 IMMUNODEPRESSIONHODGKIN’S DISEASE (*)ORGAN TRANSPLANTATIONCYTORREDUCTION THERAPYC.S.F. LEAKSH.I.V. INFECTION

(*) Two weeks before the initiation of chemotherapy or irradiation(#) children more than 2 years of age

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 21.3SOUTH 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 )

RECOMMENDED CHEMOPROPHYLAXIS FOR HIGH RISK CONTACTS AND INDEX CASES OF INVASIVE MENINGOCOCCAL DISEASE

ANTIBIOTIC DOSE DURATION EFFICACY

(%)RIFAMPIN *

< 1 MONTH 5 mg/Kg. b / d 2 d 72 - 90> 1 MONTH 10 mg/Kg. b / d 2 d

(Maximum 600 mg/Kg.)

or 20 mg / 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

RECOMMENDATIONS FOR ADMINISTRATION OFMENINGOCOCCAL 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

RECOMMENDED CHEMOPROPHYLAXIS FOR HIGH RISK CONTACTS AND INDEX CASES OF INVASIVE MENINGOCOCCAL DISEASE

THE CASE INDEX SHOULD RECEIVE CHEMOPROPHYLAXIS BEFOREDISCHARGE (UNLESS TREATED WITH CEFTRIAXONE)

CHEMOPROPHYLAXIS SHOULD BE GIVEN WITHIN 24 hs. OF CASEIDENTIFICATION (IDEALLY)

CHEMOPROPHYLAXIS IS OF LESS VALUE IF MORE THAN 2 WEEKSHAVE LAPSED AFTER THE CONTACT

OUTSIDE OF RIFAMPIN AND CEFTRIAXONE, SULFISOXASOLE (1) ANDCIPROFLOXACIN (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%)

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

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

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

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, RIFAMPINTO 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

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

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

INVASIVE MENINGOCCAL DISEASE: VACCINES IN DEVELOPPMENT

MENINGOCOCCAL B:15:P1.15 OMP VACCINE COMPLEXEDWITH GROUP C POLYSACCHARIDE (Iquique, Chile: 51% efficacy)

B:4:P1.15 OMP VACCINE and HIGH m.w. PROTEIN COMPLEXEDWITH THE GROUP C POLYS. IN CUBA: 83% EFFICACY INSTUDENTS 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

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 CHILDREN1988-9 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

23 - VALENT PNEUMOCCAL VACCINEA.C.I.P. RECOMMENDATIONS

� FUNCTIONAL OR ANATOMIC ASPLENIA �NEPHROTIC SYNDROME or C.R.F.

� SICKLE CELL DISDEASE

� IMMUNOSUPPRESSION CONDITIONSLYMPHOMAS ORGAN TRANSPLANTATIONCYTOREDUCTION THERAPYCSF LEAKSAIDS

R.O.R. Durand Hosp. 1996

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 LABORATORYSEROTYPING

SENSITIVITY TO ANTIBIOTICS

•DATA ENTRY TO EPIINFO AND WHONET PROGRAMS

•INTERNATIONAL REFERENCE LAB. (QUALITY CONTROLS)