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Biomedical subjects

R Dagan

Publications and source records attributed to R Dagan.

At least 73 records · Page 4Linked to original sources
PubMed2000

Interleukin 8 in middle ear fluid during acute otitis media: correlation with aetiology and bacterial eradication.

OBJECTIVES: To study the concentration of interleukin 8 (IL-8) in the middle ear fluid of children with acute otitis media and the association between IL-8 concentrations, aetiology of acute otitis media, and bacteriological sterilisation. STUDY DESIGN: Middle ear fluid was obtained by tympanocentesis at enrollment (day 1) and on day 4-5 in 81 children aged 3-36 months with acute otitis media who received antibiotic treatment. IL-8 concentrations were measured by enzyme linked immunosorbent assay. RESULTS: 101 samples were obtained on day 1 and 47 samples on day 4-5. 94 pathogens were isolated in 79 of 101 samples obtained on day 1: 56 Haemophilus influenzae, 35 Streptococcus pneumoniae, 2 Moraxella catarrhalis, and 1 Streptococcus pyogenes. Among 40 paired, initially culture positive samples, sterilisation was achieved on day 4-5 in 22 but not in 18 (13 H influenzae, 2 S pneumoniae, and 3 H influenzae and S pneumoniae concomitantly). IL-8 was detected in 96 of 101 and 46 of 47 samples obtained on days 1 and 4-5, respectively. Mean (SD) IL-8 concentration on day 1 was significantly higher in culture positive than in negative samples (12,636 (23,317) v 5,920 (7,080) pg/ml). In paired samples, IL-8 concentration fell in 12 of 22 ears in which sterilisation was achieved and in 9 of 21 ears with persistent or new infection. Mean (SD) IL-8 concentrations on day 4-5 were significantly higher in culture positive than in negative samples (15,420 (15,418) v 6,695 (5,092) pg/ml). CONCLUSIONS: Higher IL-8 concentrations are found in culture positive middle ear fluid in acute otitis media. Bacterial eradication is associated with a fall in these concentrations.

Acute Disease↗
PubMed2000

The effect of endogenous dehydroepiandrosterone sulphate on antibody response to hepatitis B vaccine in neonates.

BACKGROUND: DHEAS, the most abundant steroid secreted by the adrenal cortex, is suggested to have an important role in the development of immune reaction by activating T cell function and increasing antibody response, and has been tried as a vaccine adjuvant in elderly people. OBJECTIVES: We examined the correlation between endogenous DHEAS and antibody response in the neonatal period by comparing the serum DHEAS levels with the amount of antibody response against hepatitis B vaccination in neonates. METHODS: Vaccine was administered to 12 healthy infants within 24 hours of birth (day 0), and blood specimens were obtained on days 0 and 30 for determination of anti-hepatitis B surface antibody concentration and DHEAS levels. RESULTS: DHEAS levels varied widely (range 0.38-3.70 micrograms/ml, mean +/- 1SD 2.14 +/- 0.98). While we could identify two groups of patients--those with high DHEAS levels (2.90 +/- 0.56) and those with lower levels (1.30 +/- 0.56)--there was no correlation between DHEAS levels and the antibody response to hepatitis B vaccine (r = -0.05). CONCLUSIONS: In neonates, antibody response to hepatitis B vaccine does not correlate with DHEAS serum levels. These results do not support the usage of DHEAS as a vaccine adjuvant in neonates.

Dehydroepiandrosterone Sulfate↗
PubMed1999

Combined vaccination of Haemophilus influenzae type b conjugate and diphtheria-tetanus-pertussis containing acellular pertussis.

After the introduction of effective Haemophilus influenzae type b (Hib) conjugate vaccines, clinical practice has driven the development of combination vaccines comprising Hib conjugates with the infant diphtheria-tetanus-pertussis (DTP) vaccines. However, when such combinations contain an acellular pertussis component (Pa), the antibody response to Hib is lower than that with separate injections and doubts have been raised about their efficacy. We believe that such concerns are unwarranted, since the serological correlates of efficacy previously applied for Hib polysaccharide vaccines seem inappropriate for Hib conjugates. Furthermore, our own studies have shown that the lower antibody responses are not associated with impaired function of the antibodies induced, nor, and possibly more importantly, with the induction of immune memory against Hib. Therefore, with the proviso that careful clinical surveillance of Hib disease is maintained, we encourage the introduction of DTPa-Hib combinations to facilitate the inclusion of Hib into the already crowded childhood immunisation schedule.

Bacterial Capsules↗
PubMed1999

The bacteriology of the nasopharynx in childhood.

Non-typeable Haemophilus influenzae and Streptococcus pneumoniae (Pnc) are frequently isolated from the nasopharynx (NP) of young healthy children. Colonization of the NP may be detected in early infancy with peaks toward the second year of life. NP carriage of Pnc and especially of antibiotic-resistant Pnc is common and plays an important role in its spread in children, its prevalence increases in those coming into close contact, such as children attending day-care facilities. Several studies show that the presence of older siblings, antibiotic treatment during the month preceding the culture and the attendance at a large day-care center are associated with carriage of drug-resistant Pnc. Significant changes may occur early during antibiotic treatment, and these changes may vary with the use of different antibiotics. Also new strains of Pnc not detected initially emerge, and newly detected organisms are most often resistant to the administered drug. Nasopharyngeal colonization with resistant bacteria was shown to be associated with an increased incidence of acute otitis media with resistant organisms and growing incidence of unresolved otitis media. Preliminary studies show that conjugate pneumococcal vaccine might reduce the nasopharyngeal pneumococcal carriage in general, and of resistant organisms in particular.

Child↗
PubMed1999

Reactogenicity and immunogenicity of reduced antigen content diphtheria-tetanus-acellular pertussis vaccines as a booster in 4-7-year-old children primed with diphtheria-tetanus-whole cell pertussis vaccine before 2 years of age.

BACKGROUND: The recent introduction of acellular pertussis vaccines (Pa) offers the possibility of booster doses in older children and adults. This can be conveniently accomplished by combining acellular pertussis antigens with diphtheria and tetanus toxoids. However the optimal dosage for the booster injection has not yet been determined. OBJECTIVE: To compare the reactogenicity and immunogenicity of diphtheria-tetanus-acellular pertussis vaccines (DTPa) with lower antigen contents to a licensed DTPa vaccine when given at 4-7 years of age as a booster to DTPw-primed children. METHODS: Two hundred and twenty-six children primed with four doses of DTPw before 2 years of age were enrolled and allocated to three groups to receive one dose of either DTPa (Infanrix, SmithKline Beecham, Biologicals), a reduced antigen formulation of this vaccine (dtpa, SmithKline Beecham Biologicals), or an experimental low dose formulation (dtpa-exp; d and t, Michigan Biologic Products Institute). Reactogenicity was assessed using diary cards for 15 days. Immunogenicity was determined as antibody responses against the vaccine components in pre- and 1 month postvaccination sera. RESULTS: Of the 225 children who completed the study, 60.0-66.7% reported symptoms, with no significant differences in rates between groups. Local, systemic and unsolicited symptoms occurred with similar frequencies in all three groups, the vast majority (> 90%) being considered as mild or moderate. No serious adverse events related to vaccination were reported. After vaccination, all subjects displayed seroprotective concentrations against diphtheria and tetanus, and 98.7-100% had antibodies against the three pertussis component antigens. The group receiving the reduced dose of the licensed vaccine showed antibody concentrations comparable to those of the full dose group. However, the group receiving the experimental low dose formulation had statistically significantly lower antibody concentrations against both diphtheria and tetanus toxoids compared with the two other groups, as well as significantly lower anti FHA antibody concentrations. CONCLUSIONS: Reducing the antigen content of dtpa had no deleterious effect on the immunogenicity of the vaccine when given as a fifth dose at 4-7 years of age in DTPw-primed children. The reactogenicity profile of both the reduced antigen dtpa vaccines and DTPa were acceptable, the vast majority of local and systemic reactions being considered as mild to moderate, with no vaccine-related serious adverse events reported. The use of lower antigen content dtpa vaccine as a booster in children aged 4-7 is safe and immunogenic.

Antibodies, Bacterial↗
PubMed1999

Safety and immunogenicity of a new formulation of an inactivated hepatitis A vaccine.

The safety and immunogenicity of a new formulation of the inactivated hepatitis A vaccine, Avaxim, was evaluated in 189 children, aged 18 months to 15 years in a monocentric, open trial. Two vaccinations were given six months apart. Enrollment was balanced within three age groups: 18 months to 3 years, 4-8 years and 9-15 years. Antibody titers were measured blindly by an independent laboratory using a modified radioimmunoassay. Two weeks after the first dose, seroconversion was achieved by 94.6, 94.3 and 96.4% of initially HAV-seronegative subjects (antibody titre <20 mIU/ml) in each age group (youngest to oldest, respectively), with corresponding geometric mean titre concentrations (GMC) of 72.2, 54.3 and 47.1 mIU/ml. Just before the booster dose, the seroconversion rate was 100% in all groups, and the corresponding GMC values were 163, 169 and 111 mIU/ml. All groups included, a 22.6-fold rise in GMC from prebooster levels was observed four weeks after the booster dose. An explanatory analysis suggested a tendency for higher antibody levels in younger children at all vaccination time points. Local reactions were noted in 18.2% of the vaccinees after the first dose and in 8.5% after the booster dose. The rates of systemic reactions were 23.8% after the first dose and 11.4% after the booster dose. Overall, this trial demonstrated the good safety and immunogenicity profile of this vaccine in children aged 18 months to 15 years of age.

Adolescent↗
PubMed1999

Effectiveness of a nationwide infant immunization program against Haemophilus influenzae b. The Israeli Pediatric Bacteremia and Meningitis Group.

An ongoing nationwide prospective surveillance program for invasive H. influenzae b (Hib) disease in Israel enabled us to study the effectiveness of a national infant Hib immunization program, which included all infants born since January 1994. The vaccine used was Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis b (PRP-OMPC). For the cohort born during the 3 years since January 1994, the vaccine effectiveness was 94.9% for all invasive Hib diseases and 96.6% for meningitis. The efficacy in fully immunized subjects was 98.7 and 99.5%, respectively. A herd immunity effect could be observed, since a reduction in cases also occurred among infants too young to be immunized. No increase in invasive cases caused by S. pneumoniae and N. meningitidis was observed during the study period. This is the first report outside North America and Western Europe that demonstrates a nationwide extensive reduction of invasive Hib disease within a short time of the introduction of Hib conjugate vaccines to the infant immunization program.

Bacterial Outer Membrane Proteins↗
PubMed1999

Nasopharyngeal carriage of multidrug-resistant Streptococcus pneumoniae in institutionalized HIV-infected and HIV-negative children in northeastern Romania.

OBJECTIVES: The study compared nasopharyngeal carriage of resistant pneumoniae in human immunodeficiency virus (HIV)-seropositive and -seronegative children. METHODS: Nasopharyngeal colonization with Streptococcus pneumoniae was investigated during May 1996 in 162 HIV-negative infants and children (age range, 1-38 mo) and 40 HIV-infected children (age range, 39-106 mo) living in an orphanage in Iasi, northeastern Romania. The HIV-infected children lived separated from the other children and were cared for by a different staff. Streptococcus pneumoniae was isolated from 12 of 40 (30%) HIV-infected and from 81 of 160 (50%) HIV-negative children. Antimicrobial susceptibility to penicillin and ceftriaxone was determined by E-test, and to another five antibiotics by disk diffusion. Serotyping was performed by the Quellung method on 81 of 93 (87%) isolates. RESULTS: Serotypes 6A, 6B, 19A, and 23F together represented 98% of all isolates. Ninety-nine percent of S. pneumoniae isolates were resistant to penicillin, and 74% were highly resistant to penicillin (minimum inhibitory concentration [MIC] > 1 mg/mL); MIC50 and MIC90 to penicillin of the isolates were 2 mg/mL and 8 mg/mL, respectively. Eighty-nine of ninety-one isolates were susceptible to ceftriaxone; 99%, 87%, 87%, 48%, and 21% of the isolates were resistant to trimethoprim-sulphamethoxazole, erythromycin, clindamycin, tetracycline, and chloramphenicol, respectively. Eighty-two (89%) isolates were multidrug resistant (resistant to =/>3 antibiotic classes); 37 of 92 (40%) isolates were resistant to 5 or more antibiotic classes, and 16 of these 37 (43%) belonged to serotype 19A. All serotype 19 isolates were highly resistant to penicillin. CONCLUSIONS: No significant differences were observed in the resistance rates of S. pneumoniae in HIV-infected children compared to HIV-negative children. Multidrug-resistant pneumococci were highly prevalent in this Romanian orphanage in both HIV-negative and older HIV-infected children. The observed high prevalence of multidrug-resistant pneumococci (coupled with high penicillin resistance) with a limited number of circulating serotypes emphasizes the need to further evaluate the conjugate vaccines in children at risk for invasive pneumococcal infection.

Anti-Bacterial Agents↗
PubMed1999

Marked differences in pneumococcal carriage and resistance patterns between day care centers located within a small area.

Carriage rates of Streptococcus pneumoniae and their antibiotic resistance, capsular types, and genetic patterns were studied among 264 children aged 12-35 months attending 8 day care centers located within a 2.5-mile radius in the same city. Nasopharyngeal cultures were obtained within a 2-month interval from all 264 children. Significant differences in each of the studied characteristics were found between day care centers, and each day care center had a unique pattern of the carried pneumococci. Our findings show that day care centers are independent microenvironments and emphasize their role in the transmission and augmentation of antibiotic-resistant S. pneumoniae in the community.

Carrier State↗
PubMed1999

Safety and immunogenicity of Shigella sonnei and Shigella flexneri 2a O-specific polysaccharide conjugates in children.

O-specific polysaccharide conjugates of shigellae were safe and immunogenic in young adults, and a Shigella sonnei conjugate conferred protection [1-3]. Shigellosis is primarily a disease of children; therefore, the safety and immunogenicity of S. sonnei and Shigella flexneri 2a conjugates were studied in 4- to 7-year-old children. Local and systemic reactions were minimal. The first injection of both conjugates elicited significant rises in geometric mean levels of serum IgG only to the homologous lipopolysaccharide (LPS) (S. sonnei, 0.32-8.25 ELISA units [EU]; S. flexneri 2a, 1.15-20.5 EU; P<.0001). Revaccination at 6 weeks induced a booster response to S. flexneri 2a LPS (20.5-30.5 EU, P=.003). Six months later, the geometric mean levels of IgG anti-LPS for both groups were higher than the prevaccination levels (P<.0001). Similar, but lesser, rises were observed for IgM and IgA anti-LPS. The investigational Shigella conjugates were safe and immunogenic in children and merit evaluation of their efficacy.

Antibodies, Bacterial↗
PubMed1999

Interference of antibody production to hepatitis B surface antigen in a combination hepatitis A/hepatitis B vaccine.

A randomized trial comparing 3 manufacturing consistency lots of a combination hepatitis A/hepatitis B vaccine to each other and to hepatitis A vaccine and hepatitis B vaccine given separately and concurrently was done to evaluate safety, tolerability, and immunogenicity. Healthy volunteers >/=11 years of age were divided into 4 groups. Each of 3 groups received a separate consistency lot of the combination vaccine, and 1 group received separate but concurrent injections of hepatitis A and hepatitis B vaccines. Injections were given at weeks 0 and 24. The combination vaccine was generally well tolerated. The hepatitis A portion of the combination vaccine produced clinically acceptable high seropositivity rates 4 and 52 weeks after the first injection. The hepatitis B portion of the vaccine did not produce clinically acceptable seropositivity rates 4 weeks after the second injection. Lack of antibody production may be attributed, at least in part, to immunologic interference.

Adolescent↗
PubMed1999

Evaluation of screening for hepatitis B surface antigen during pregnancy in a population with a high prevalence of hepatitis B surface antigen-positive/hepatitis B e antigen-negative carriers.

BACKGROUND: Universal hepatitis B vaccination in infancy was implemented in Israel in 1992. The program consists of active vaccination at birth and at 1 and 6 months of age, without hepatitis B surface antigen (HBsAg) screening during pregnancy. Infants of HBsAg carrier mothers do not receive specific hepatitis B immunoglobulin in addition to vaccine at birth. The recently arrived Jewish immigrants from Ethiopia are the group with the highest rate of HBsAg carriage (approximately 10%) in Israel. AIM: The objective of this study was to evaluate whether the present policy is effective against perinatal HBV transmission from mothers of Ethiopian origin to their infants. METHODS: The study group included 411 Israeli born children, offspring of mothers of Ethiopian origin. All infants were fully vaccinated starting at birth. Sera were collected from the children at the age of 9 to 36 months and from their mothers. Tests for HBsAg, antibodies to HBsAg (anti-HBs) and antibodies to hepatitis B core antigen (anti-HBc) were performed. RESULTS: Eighty-nine percent of the children had detectable anti-HBs, including 82.2% with protective anti-HBs concentrations (> or =10 mIU/ ml). Although 24 mothers (6.2%) were HBsAg carriers, none of the children was HBsAg-positive. Seven of 394 infants (1.7%) tested positive for anti-HBc. This test became negative in 5 of 6 who were followed for 12 months. The percentage of infants with protective anti-HBs concentrations decreased significantly from 91.4% at 9 to 12 months to 70.1% at 31 to 36 months of age. The mother's infection status was not associated with the infant's response to vaccine. Calculation based on the above data suggests that screening for HBsAg in pregnancy in that group is not cost-effective. CONCLUSIONS: Our results suggest that the Israeli vaccination program against HBV infection is effective, even in a high risk population, and additional measures are not cost-effective.

Carrier State↗
PubMed1999

Short course therapy with cefuroxime axetil for acute otitis media: results of a randomized multicenter comparison with amoxicillin/clavulanate.

BACKGROUND: Otitis media is a common infection of childhood. Increasing antibiotic resistance rates among the principal causative pathogens, Streptococcus pneumoniae and Haemophilus influenzae, are associated with failure of first line agents. OBJECTIVE: This open, randomized, multicenter study compared the clinical efficacy of a short 5-day course of cefuroxime axetil (CAE) suspension with that of amoxicillin/clavulanate (A/CA) suspension for 8 or 10 days. METHODS: Children age 6 to 36 months with acute otitis media with effusion, diagnosed by tympanocentesis and microbiologic culture, were randomized to receive CAE (30 mg/kg/day in two divided doses for 5 days) or A/CA 40 mg/kg/day in three divided doses for 10 days (A/CA-10). In French centers A/CA was given at 80 mg/kg/day in three divided doses for 8 days (A/CA-8). Patients were assessed 1 to 4 days after completing the course (posttreatment) and followed up at 21 to 28 days after completing the course. RESULTS: Of the 716 patients randomized, 252 were treated with CAE, 255 with A/CA-10 and 209 with A/CA-8. In the clinically evaluable population, the proportions of patients with clinical cure at posttreatment were 175 of 203 (86%), 181 of 205 (88%) and 145 of 164 (88%) in the CAE, A/CA-10 and A/CA-8 groups, respectively, demonstrating equivalence among the three treatments. For patients <18 months old, clinical cures were 111 of 134 (83%), 116 of 131 (89%) and 83 of 99 (84%) in the CAE, A/CA-10 and A/CA-8 groups, respectively; equivalence was also demonstrated. At follow-up, 130 of 175 (74%) CAE, 121 of 172 (70%) A/CA-10, and 112 of 142 (79%) A/CA-8 had maintained cure. A total of 837 pretreatment pathogens were isolated from middle ear fluid in 73% (522 of 716) patients, the majority of isolates were S. pneumoniae (30%) and H. influenzae (27%). The most common adverse events were gastrointestinal, the incidence of drug-related diarrhea being higher in the A/CA-10 group (18%) than in either the CAE or A/CA-8 groups (10%). CONCLUSIONS: A 5-day course of CAE, given twice daily, was shown to be equivalent to the two regimens of A/CA for treatment of acute otitis media with effusion in children.

Acute Disease↗
PubMed1998

Outpatient management of acute mastoiditis with periosteitis in children.

Children with acute mastoiditis with periosteitis are conventionally hospitalized for parenteral antibiotics and/or surgical treatment. However, if possible, effective and safe outpatient treatment is desirable. During a 36-month period, outpatient parenteral antibiotic therapy (once daily i.m. ceftriaxone) was evaluated in 32 children with acute mastoiditis, with clinical evidence of periosteitis. Inclusion criteria included otomicroscopic evidence of acute otitis media (AOM), displacement of the pinna, retroauricular swelling, erythema and tenderness. The treatment consisted of wide myringotomy and administration of i.m. antibiotics. Daily visits, by a combined team of an otolaryngologist and pediatric infectious disease specialist, were considered essential. Fourteen children (43%) were treated initially in the hospital (and subsequently as outpatients) and 18 (57%) children were treated entirely as outpatients. Mean duration of outpatient treatment was 7 days (range: 4-10). The overall clinical cure rate was 96.8%. One child underwent simple mastoidectomy. No serious side effects were observed. Our data suggests that many children with acute mastoiditis with periosteitis can be managed successfully and safely as outpatients by a combined team of otolaryngologists and infectious disease specialists.

Acute Disease↗
PubMed1998

Antibiotic resistance pattern of enterotoxigenic Escherichia coli isolated from infants and young adults in Israel.

The aim of this study was to describe antibiotic resistance rates of enterotoxigenic Escherichia coli in Israel in order to facilitate the empirical choice of antibiotic treatment or prophylaxis for traveler's diarrhea and infantile diarrhea in our region. A total of 281 enterotoxigenic Escherichia coli isolates were tested: 144 from Bedouin infants and 137 from Israeli soldiers. Antibiotic-resistant isolates were prevalent in both groups, but higher resistance rates were found in the pediatric group. Strains producing heat-labile toxin showed higher resistance rates than strains producing heat-stable toxin. The results obtained in Israel preclude the use of many commonly used antibiotics for the treatment of traveler's diarrhea. Quinolones, however, are still effective.

Adolescent↗