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Biomedical subjects

Ron Dagan

Publications and source records attributed to Ron Dagan.

At least 19 recordsLinked to original sources
PubMed2007

Elimination of hepatitis a infection outbreaks in day care and school settings in southern Israel after introduction of the national universal toddler hepatitis a immunization program.

BACKGROUND: In 1999, Israel became the first country to begin universal toddler immunization against hepatitis A infection with a 2-dose schedule at 18 and 24 months. The effect of the Israeli program on outbreaks of Hepatitis A in day care and school settings was studied. METHODS: The records of all hepatitis A illness outbreaks in day care and school settings reported to the Ministry of Health in Southern Israel during 1993 through 2005 were reviewed. The number of exposed contacts for whom postexposure prophylaxis was administered was retrieved from records of epidemiologic investigations. Rates of immunization coverage were extracted from records of Maternal and Child Health Clinics. RESULTS: Three hundred nineteen cases of hepatitis A illness during the years 1993 through 2005 were associated with 113 outbreaks in day care and school settings of which 92% occurred before the institution of universal toddler immunization. Since 2000, no hepatitis A infection outbreaks have been reported in any day care and school settings in the region. An average of 732 children received immunoglobulin prophylaxis yearly because of exposure to an outbreak in an educational setting during the preimmunization period, 106 in 2000 and zero in the 5 years since 2001. The data showed marked herd immunity since school-aged children born before 1999 were not immunized, but elimination of outbreaks occurred equally in that age group. Immunization coverage was 86.4% for one dose of hepatitis A vaccine by age 3 years and 77.3% for 2 doses among the birth cohort of 2000. CONCLUSIONS: Universal hepatitis A immunization of toddlers was associated with disappearance of outbreaks in educational settings. This included cohorts of nonimmunized children representing marked herd immunity.

Adolescent↗
PubMed2006

The important role of nontypable Streptococcus pneumoniae international clones in acute conjunctivitis.

BACKGROUND: In a recent epidemiological study in southern Israel, nontypable Streptococcus pneumoniae isolates were found to be highly associated with sporadic cases of acute conjunctivitis (AC). The purpose of the present study was to evaluate the relative importance in causing AC of the absence of capsule versus genotype properties. METHODS: DNA typing by pulsed-field gel electrophoresis (PFGE) was performed on 148 nontypable organisms isolated from 3 sites: nasopharynx of healthy children, middle-ear fluid, and conjunctiva. RESULTS: Analysis of the PFGE patterns revealed the presence of 6 clusters; 2 clusters that included 44% of the isolates (65/148) were associated with AC, and the remaining 4 were frequently isolated from the nasopharynx. Multilocus sequence typing, performed on representative isolates of the 2 major clusters, confirmed that the organisms were pneumococci; one is a single-locus variant of sequence type (ST) 448, and the other is related to ST344. Both types appear to be members of pneumococcal lineages that have lost capsular loci. The nontypable isolates showed high rates of resistance to antimicrobial agents. CONCLUSIONS: Our data suggest that the absence of the capsule--along with other, yet-unidentified genetic characteristics--provide S. pneumoniae with a selective virulence advantage in conjunctivitis.

Bacterial Typing Techniques↗
PubMed2006

The contribution of smoking and exposure to tobacco smoke to Streptococcus pneumoniae and Haemophilus influenzae carriage in children and their mothers.

BACKGROUND: Exposure to tobacco smoke is associated with higher risk of Streptococcus pneumoniae and Haemophilus influenzae infection. The aim of this study was to determine the influence of smoking and exposure to tobacco smoke on S. pneumoniae and H. influenzae carriage rates in children and their mothers. PATIENTS AND METHODS: We performed a cross-sectional surveillance study of nasopharyngeal and oropharyngeal carriage of S. pneumoniae and H. influenzae in 208 children aged <60 months and their mothers. Smoking exposure and medical history were recorded. Carriage rates for children and their mothers in nasopharyngeal and oropharyngeal specimens were analyzed on the basis of smoking exposure. RESULTS: The S. pneumoniae carriage rate was higher among children exposed to smoking than among nonexposed children (76% vs. 60%; P=.016). Exposed children more frequently carried S. pneumoniae serotypes included in the conjugate 7-valent vaccine, compared with nonexposed children (49% vs. 30% of all S. pneumoniae-positive nasopharyngeal cultures; P=.02). Carriage rates of S. pneumoniae were higher among mothers who smoked than among mothers exposed to smoking and among nonexposed mothers (32%, 15%, and 12%, respectively; P=.03). There were no differences in H. influenzae carriage rates between children and mothers from smoking and nonsmoking families. CONCLUSIONS: Exposure to tobacco smoke increased S. pneumoniae carriage rates in general and for carriage of serotypes included in the conjugate 7-valent vaccine in particular in children. Smoking mothers had a higher S. pneumoniae carriage rate than did nonsmoking mothers. Smoking or exposure to smoking did not increase H. influenzae carriage rates in children and mothers.

Adult↗
PubMed2006

Community-acquired bloodstream infections in children > one month old in southern Israel (1992-2001): epidemiological, clinical and microbiological aspects.

We studied the epidemiology, microbiology, clinical picture and outcome of community-acquired bloodstream infections (CABI) in children in southern Israel during 1992-2001. Information was collected prospectively by daily surveillance. CABI was diagnosed when a positive blood culture was reported in a patient discharged from the emergency room or during <48 h since admission if hospitalized. There were 1439 CABI episodes in 1396 children aged 1 month to 14 y. CABI incidence was 100/100,000 children with no increase during the study period. Risk of CABI was 3.8 times higher in a Bedouin than in a Jewish child. 1561 bacteria (793, 50%, gram-positive and 768, 49% gram-negative organisms, respectively) and 13 fungi were recovered. Most frequent gram-positive organisms were Streptococcus pneumoniae (509 isolates, 32% of all isolates, 64% of all gram-positive), Staphylococcus aureus (137, 9%, 17%) and Streptococcus pyogenes (46, 3%, 6%). Enterobacteriaceae spp. were the most frequent gram-negative pathogens (279, 18%, 36%), followed by Brucella (205, 13%, 27%). S. pneumoniae was the most common pathogen in children <12 months and 1-5 y age; Brucella was the most frequent pathogen in children >5 y of age. Coverage of 7-valent pneumococcal conjugated vaccine for CABI was 38.5%. 38 (2.7%) patients died; 16 cases were caused by S. pneumoniae.

Adolescent↗
PubMed2006

A multicenter, open label, double tympanocentesis study of high dose cefdinir in children with acute otitis media at high risk of persistent or recurrent infection.

BACKGROUND: Given the relatively high prevalence of recurrent and persistent acute otitis media (AOM) and the prominent etiologic role of Streptococcus pneumoniae, especially penicillin-nonsusceptible strains in children with these conditions, new alternative treatments are desirable. METHODS: Children 6 months-4 years of age with AOM considered to be at risk for recurrent or persistent infection received large dosage cefdinir 25 mg/kg oral suspension once daily for 10 days. Children were evaluated pretreatment (day 1), on therapy (days 4-6), end of therapy (days 12-14) and at follow-up (days 25-28). All children had tympanocentesis at enrollment. In culture-positive children, tympanocentesis was repeated after 3-5 days (days 4-6) unless evidence of absence of middle ear effusion was documented. RESULTS: Of 447 children enrolled, 230 were clinically and bacteriologically evaluable (74% 2 years old or younger; 57% treated for AOM in previous 3 months). Bacteriologic eradication, based on repeat tympanocentesis on days 4-6, was achieved in 74% (170 of 230) of children; 76% (201 of 266) of AOM pathogens were eradicated. Eradication of penicillin-susceptible, -intermediate and -resistant S. pneumoniae was 91% (50 of 55), 67% (18 of 27) and 43% (10 of 23), respectively (P < 0.001); eradication of H. influenzae was 72% (90 of 125). Overall clinical response at days 12-14 was 83% (76 and 82% for children with S. pneumoniae and Haemophilus influenzae, respectively). Sustained clinical response at days 25-28 was 85%. Clinical response was 83% for culture-positive children versus 96% for culture-negative children at baseline tympanocentesis (P < 0.001). CONCLUSIONS: In this study of AOM among children at risk for persistent or recurrent infection, large dose cefdinir resulted in an overall successful clinical response at end of treatment of 83%. This regimen was efficacious against penicillin-susceptible S. pneumoniae, but effectiveness was markedly decreased against nonsusceptible strains and was moderate for H. influenzae strains.

Acute Disease↗
PubMed2006

Comparison of human metapneumovirus, respiratory syncytial virus and influenza A virus lower respiratory tract infections in hospitalized young children.

BACKGROUND: We compared the clinical and demographic features of children with lower respiratory tract infection (LRI) caused by human metapneumovirus (HMPV), respiratory syncytial virus (RSV) and influenza A virus and sought to determine whether coinfection by HMPV and other respiratory viruses leads to increased disease severity. METHODS: Nasal wash specimens were prospectively obtained from 516 children hospitalized for LRI during a 1-year period and tested for the presence of HMPV by reverse transcription-polymerase chain reaction and for RSV and influenza A by direct immunofluorescence. RESULTS: HMPV was detected in 68 (13%) patients and was the third most common viral pathogen; 16 of 68 HMPV-positive children (24%) had coinfection with other respiratory viruses (HMPVco).HMPV patients were older than RSV patients (17.6 +/- 16.8 months versus 10.5 +/- 11.8 months, P = 0.02). HMPV was associated with wheezing and hypoxemia at a rate similar to that of RSV and higher than that of influenza A. Atelectasis was more common among HMPV (40%) than among RSV and influenza patients (13%, P < 0.05 for each). HMPV infection was more often associated with a diagnosis of pneumonia than RSV and influenza A and was more often associated with a diagnosis of asthma and less often associated with a diagnosis of bronchiolitis than RSV infection (P < 0.05 for each), even when corrected for age. Children with HMPVco had a higher rate of gastrointestinal symptoms but did not show a more severe respiratory picture. CONCLUSIONS: The clinical pattern of HMPV more closely resembles that of RSV than that of influenza A LRI, yet the differences in age, radiographic findings and clinical diagnosis suggest that HMPV pathogenesis may differ from that of RSV.

Animals↗
PubMed2006

Site-specific disease potential of individual Streptococcus pneumoniae serotypes in pediatric invasive disease, acute otitis media and acute conjunctivitis.

BACKGROUND: Recent studies have shown that some Streptococcus pneumoniae serotypes possess a higher potential to cause invasive disease than others. However, it is unknown whether disease potential for specific serotypes is similar for mucosal disease. Our objective was to assess the disease potential of individual S. pneumoniae serotypes causing invasive pneumococcal disease (IPD), acute otitis media (AOM) and acute conjunctivitis (AC) in children. METHODS: Serotypes of pneumococcal isolates from children with IPD, AOM and AC were compared with those carried by healthy children aged <3 years. All children resided in the same area and were studied during the same period. Odds ratios for disease were calculated for each diagnosis following multivariate analysis, including gender, age, ethnic group, previous antibiotic treatment and year variability. RESULTS: A total of 5,500 isolates were collected: 189 from blood or cerebrospinal fluid, 3,200 from middle ear fluid, 348 from conjunctiva and 1,763 from nasopharynx of healthy children. A significant positive association with IPD was demonstrated for serotypes 1, 5 and 12F; with AOM for serotypes 1, 3, 5, 12F, 19A and 19F; and with AC for serotype 3 and nontypeable S. pneumoniae. A significant negative association with IPD was demonstrated for nontypeable S. pneumoniae and with AOM for serotypes 6A, 6B, 15A and nontypeable S. pneumoniae. CONCLUSIONS: Our results reflect the importance of the polysaccharide capsule in site-specific disease potential and provide useful information regarding disease potential of nonvaccine serotypes shown to be involved in carriage replacement after vaccination with the 7-valent conjugate vaccine.

Acute Disease↗
PubMed2006

Will reduction of antibiotic use reduce antibiotic resistance?: The pneumococcus paradigm.

Community-acquired respiratory infections in general, and those caused by S. pneumoniae in particular, are the main reason for prescribing antimicrobials in young children. Antibiotic drug abuse is common. This is the basis for the initiative for the reduction in antibiotic use. However, failure to consider that not all antibiotics are similar in their effect on promotion of resistance has led to continuous emerging resistance. In the present article, the trends in prescribing antibiotics in young children and their interrelation with antibiotic resistance among clinical respiratory isolates of S. pneumoniae in children will be reviewed, along with theoretical considerations and research evidence that led to concluding that among antibiotics, the least resistance-promoting drug for S. pneumoniae is amoxicillin (+/- clavulanate), whereas oral cephalosporins and azithromycin demonstrate a higher resistance-promotion potential in the individual population in the community. Although antibiotics differ in their resistant-promotion potential, all still do promote resistance.

Anti-Bacterial Agents↗
PubMed2006

An open-label, double tympanocentesis study of levofloxacin therapy in children with, or at high risk for, recurrent or persistent acute otitis media.

BACKGROUND: Levofloxacin has excellent activity against common respiratory pathogens and therefore is likely to be effective in treating children with persistent or recurrent otitis media. OBJECTIVE: The objective of this study was to assess the efficacy and safety of levofloxacin treatment in the eradication of bacterial pathogens from the middle ear fluid (MEF) of children with, or at high risk for, persistent or recurrent otitis media. METHODS: An open-label multicenter trial was conducted that involved tympanocentesis at entry and selectively 3 to 5 days after starting levofloxacin (10 mg/kg twice a day for 10 days). RESULTS: : Two hundred five children (80% < or =2 years) were enrolled. One child did not have a confirmed diagnosis of acute otitis media and did not return for follow-up visits. Of the remaining 204 children, 94 (46%) had bilateral infection and 63 (31%) were receiving antimicrobials immediately before entry. One hundred five isolates of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus. pyogenes were recovered in pure or mixed cultures. All isolates were susceptible to levofloxacin. During-treatment bacterial eradication from MEF occurred in 88% (78 of 89) of bacteriologically evaluable patients, including 90% (65 of 72) of children < or =24 months of age. Bacteria initially isolated from MEF were eradicated in 31 of 37 (84%) children infected with S. pneumoniae and in 54 of 54 (100%) children infected with H. influenzae. Overall, clinical success rate after therapy was 94% for the total study population and 92% for the bacteriologically evaluable population. Levofloxacin was well tolerated. Vomiting (4%) was the most common treatment-limiting adverse event. CONCLUSIONS: Levofloxacin was safe and effective in treating and eradicating common bacterial pathogens from MEF in children with, or at risk for, recurrent or persistent otitis media.

Acute Disease↗
PubMed2006

Nasopharyngeal colonization: a target for pneumococcal vaccination.

The pneumococcal conjugate vaccine (PCV), licensed in 2000, is highly efficient in preventing serious disease caused by serotypes in the vaccine and also prevents symptomless colonization of the nasopharynx. Prevention of this first step in the infection cycle has important consequences: it reduces chances of spread of the infection and indirectly protects from disease. Through these indirect effects, the protection afforded by the vaccine extends to the whole population, including those not vaccinated (herd immunity). Already now, after 5 years of wide use of PCV for infant immunization in the USA, more cases are prevented through the indirect effects than by vaccine-induced immunity in those vaccinated. The extended protection increases the cost-effectiveness of PCV and should clearly encourage its use in poorly resourced countries. However, the accumulated experience also shows that the herd immunity, due to PCV, is partly offset by replacement of the vaccine serotypes by other, nonvaccine serotypes. Owing to the general reduced virulence of the latter, this has only had a modest effect on disease, but the possibility of more virulent nonvaccine serotypes arising cannot be ignored and should be the focus of continued surveillance.

Animals↗
PubMed2005

The vaccine potential of Streptococcus pneumoniae surface lectin- and non-lectin proteins.

We have fractionated S. pneumoniae surface proteins into lectin and non-lectin fractions and tested their ability to elicit protective immune responses in the mouse model system. The total cell wall protein fraction (CW-T) was separated into lectin (CW-L), and non-lectin (CW-NL) fractions and used for immunization of mice. Immunized mice were challenged intranasally or intraperitoneally with S. pneumoniae strain WU2 (serotype 3). CW-T, CW-NL and CW-L and adjuvant only vaccination protected 55%, 43%, 44% and 0% of the intranasally challenged mice, respectively and 67%, 86%, 11% and 0% of mice challenged intraperitoneally, respectively. Immunogenic proteins in each fraction were sequenced and identified using MALDI-TOF. CW-L proteins provided a significantly better protection against intranasal inoculation and CW-NL proteins provided a significantly better protection from intraperitoneal inoculation. Proteins identified by sera from mice immunized with the cell-wall derived fractions may constitute candidates for future development of anti S. pneumoniae vaccines.

Animals↗
PubMed2005

Immunogenicity of an inactivated hepatitis A pediatric vaccine: three-year post-booster follow-up.

The persistence of anti-hepatitis A virus antibody concentrations was followed over 3 years in 177 healthy children following primary and booster vaccination with an inactivated hepatitis A vaccine, Avaxim 80 pediatric. Seroconversion rates (post-immunization anti-HAV antibody concentration >or=20 mIU/mL) and geometric mean concentrations (GMC) were estimated for each of three age groups: 18 month--3 years, 4--8 years, and 9--15 years. Only subjects who were initially HAV-seronegative at inclusion (<20 mIU/mL) were analyzed. Follow-up visits at years 1, 2, and 3 involved 177, 149, and 135 children, respectively. A decline in GMCs of about 74% occurred during the first year, from 3,060 to 814 mIU/mL overall, but did not continue during years 2 and 3. All subjects remained seropositive (antibody concentration >or=20 mIU/mL), with overall GMCs of 814, 891, and 924 mIU/mL in years 1--3, respectively. The inactivated hepatitis A study-vaccine resulted in sustained seroprotective antibody concentrations in 100% of these children, without a significant decline in antibiotic concentrations over the 3 years following booster injection, thus demonstrating the long-term protection expected with this vaccine.

Adolescent↗
PubMed2005

Nutritional status and diarrheal illness as independent risk factors for alveolar pneumonia.

Community-acquired alveolar pneumonia (CAAP) is typically associated with bacterial infections and is especially prevalent in vulnerable populations worldwide. The authors studied nutritional status and diarrheal history as risk factors for CAAP in Bedouin children <5 years of age living in Israel. In this prospective case-control study (2001-2002), 334 children with radiographically confirmed CAAP were compared with 529 controls without pneumonia with regard to nutritional status and diarrhea history. Controls were frequency matched to cases on age and enrollment month. Logistic regression models were used to evaluate associations of CAAP with nutritional status and recent diarrhea experience. Anemia (adjusted odds ratio (AOR) = 3.32, 95% confidence interval (CI): 2.24, 4.94; p < 0.001), low birth weight (AOR = 2.16, 95% CI: 1.32, 3.54; p = 0.002), stunting (AOR = 2.22, 95% CI: 1.31, 3.78; p = 0.004), serum retinol concentration (AOR = 1.03 per microg/dl, 95% CI: 1.02, 1.05; p < 0.001), and having > or =1 diarrhea episodes within 31 days prior to enrollment (AOR = 2.30, 95% CI: 1.26, 4.19; p = 0.007) were identified as risk factors for CAAP. Results suggest that improving antenatal care and the nutritional status of infants may reduce the risk of CAAP in Bedouin children. Furthermore, they suggest that vaccines developed to prevent diarrhea may also lower the risk of CAAP.

Anemia↗
PubMed2005

Functional activity of antibodies after immunization of Finnish and Israeli infants with an 11-valent pneumococcal conjugate vaccine.

Finnish and Israeli infants received an 11-valent mixed carrier pneumococcal conjugate vaccine (11PCV) with or without aluminum adjuvant at the age of 2, 4, 6, and 12 months. We measured opsonophagocytic activity (OPA) of antibodies to pneumococcal strains of serotypes 4, 6B, 14, 19F, and 23F. At 7 months, OPA was clearly detected for all the serotypes. At 13 months, OPAs increased further and the proportion of individuals with a positive OPA ranged between 81 and 100%. The adjuvant improved functional activity of antibodies to serotype 6B pneumococci. In conclusion, immunization of infants with the 11PCV induced functionally active antibodies.

Adjuvants, Immunologic↗
PubMed2005

Incidence of hepatitis A in Israel following universal immunization of toddlers.

CONTEXT: In Israel, the mean annual incidence of hepatitis A disease was 50.4 per 100 000 during 1993-1998. A 2-dose universal hepatitis A immunization program aimed at children aged 18 and 24 months (without a catch-up campaign) was started in 1999. OBJECTIVE: To observe the impact of toddlers-only universal vaccination on hepatitis A virus disease in Israel. DESIGN AND SETTING: Ongoing passive national surveillance of hepatitis A cases in Israel has been conducted since 1993 by the Ministry of Health. An active surveillance program in the Jerusalem district in 1999-2003 provided validation for the passive program. MAIN OUTCOME MEASURE: Incidence of reported hepatitis A disease, 1993-2004. RESULTS: Overall vaccine coverage in Israel in 2001-2002 was 90% for the first dose and 85% for the second dose. A decline in disease rates was observed before 1999 among the Jewish but not the non-Jewish population. After initiation of the program, a sharp decrease in disease rates was observed in both populations. The annual incidence of 2.2 to 2.5 per 100 000 during 2002-2004 represents a 95% or greater reduction for each year with respect to the mean incidence during 1993-1998 (P<.001). For children aged 1 through 4 years, a 98.2% reduction in disease was observed in 2002-2004, compared with the prevaccination period (P<.001). However, a sharp decline was also observed in all other age groups (84.3% [<1 year], 96.5% [5-9 years], 95.2% [10-14 years], 91.3% [15-44 years], 90.6% [45-64 years], and 77.3% [>or=65 years]). Among the Jewish population in the Jerusalem district, in whom the active surveillance program was successfully conducted, a more than 90% reduction of disease was demonstrated. Of the 433 cases reported nationwide in 2002-2004 in whom vaccination status could be ascertained, 424 (97.9%) received no vaccine and none received 2 doses. CONCLUSION: This universal toddlers-only immunization program in Israel demonstrated not only high effectiveness of hepatitis A vaccination but also marked herd protection, challenging the need for catch-up hepatitis A vaccination programs.

Adolescent↗
PubMed2005

Safety and efficacy of gatifloxacin therapy for children with recurrent acute otitis media (AOM) and/or AOM treatment failure.

BACKGROUND: Because of concerns about arthrotoxicity, fluoroquinolones are restricted for use in children. This study describes the safety and efficacy of gatifloxacin when used for treatment of children with recurrent acute otitis media (ROM) or acute otitis media (AOM) treatment failure (AOMTF). METHODS: We performed an analysis of 867 children included in 4 clinical trials who had ROM and/or AOMTF and were treated with gatifloxacin (10 mg/kg once daily for 10 days). RESULTS: Gatifloxacin had adverse event rates that were similar overall to those of a comparator antibiotic (amoxicillin-clavulanate), except for increased diarrhea in children <2 years old receiving amoxicillin-clavulanate. There was no evidence of arthrotoxicity, hepatotoxicity, alteration of glucose homeostasis, or central nervous system toxicity acutely or during 1 year follow-up in any child. Regarding efficacy, in 2 noncomparative trials, the gatifloxacin cure rate of AOM was 89% (95% confidence interval [CI], 83%-95%) at the test of cure (TOC) visit, 3-10 days after completion of therapy. In 2 comparative trials of gatifloxacin versus amoxicillin-clavulanate, the efficacy of gatifloxacin was 88% (95% CI, 82%-94%). Gatifloxacin led to better clinical outcomes than amoxicillin-clavulanate for AOMTF (91% vs. 81%; P=.029), for AOMTF and age <2 years old (89% vs. 69%; P=.009), and for severe AOM in children <2 years old (90% vs. 75%; P=.012). Among children with AOMTF previously treated with amoxicillin-clavulanate or ceftriaxone injections, gatifloxacin cure rates were high (88% and 75%, respectively). CONCLUSIONS: Gatifloxacin appears to be safe for children, with no evidence of producing arthrotoxicity in 867 children exposed to the antibiotic when used as treatment for ROM and AOMTF.

Anti-Infective Agents↗