Outcomes and toxicities in oligometastatic patients treated with stereotactic body radiotherapy for adrenal gland metastases: A multi-institutional retrospective study.

BACKGROUND: Studies reporting SBRT outcomes in oligometastatic patients with adrenal gland metastases (AGM) are limited. Herein, we present a multi-institutional analysis of oligometastatic patients treated with SBRT for AGM. MATERIAL/METHODS: The Consortium for Oligometastases Research (CORE) is among the largest retrospective series of patients with oligometastases. Among CORE patients, those treated with SBRT for AGM were included. Clinical and dosimetric data were collected. Adrenal metastatic burden (AMB) was defined as the sum of all adrenal GTV if more than one oligometastases is present.Competing risk analysis was used to estimate actuarial cumulative local recurrence (LR) and widespread progression (WP). Kaplan-Meier method was used to report overall survival (OS), local recurrence-free survival (LRFS), and progression-free survival (PFS). Treatment related toxicities were also reported. RESULTS: The analysis included 47 patients with 57 adrenal lesions. Median follow-up was 18.2 months. Median LRFS, PFS, and OS were 15.3, 5.3, and 19.1 months, respectively. A minimum PTV dose BED10 > 46 Gy was associated with an improved OS and LRFS. A prescribed BED10 > 70 Gy was an independent predictor of a lower LR probability. AMB>10 cc was an independent predictor of a lower risk for WP. Only one patient developed an acute Grade 3 toxicity consisting of abdominal pain. CONCLUSION: SBRT to AGM achieved a satisfactory local control and OS in oligometastatic patients. High minimum PTV dose and BED10 prescription doses were predictive of improved LR and OS, respectively. Prospective studies are needed to determine comprehensive criteria for patients SBRT eligibility and dosimetric planning.

Incidence of respiratory syncytial virus bronchiolitis in hospitalized infants born at 33-36 weeks of gestational age compared with those born at term: a retrospective cohort study.

OBJECTIVE: The aim was to compare incidences of respiratory syncytial virus (RSV) bronchiolitis in late preterm vs. term infants (33-36 vs. >36 weeks of gestational age (WGA)). METHODS: This was a population-based retrospective study including all infants <12 months hospitalized at Soroka medical centre with bronchiolitis between 2004 and 2012. Infants with comorbidities were excluded. RSV bronchiolitis rates were calculated by extrapolating the proportion of positive tests among tested infants. Population denominator for incidence rates was calculated from hospital records. RESULTS: During the study, 374 late preterm and 2948 term infants were hospitalized with bronchiolitis. Out of 229 (61.2%) late preterm infants and 1738 (59%) term infants tested for RSV, 164 (71.6%) and 1266 (72.8%) were positive for RSV respectively. The mean yearly incidences per 1000 children of RSV bronchiolitis hospitalizations of late preterm and term infants were 35.8 ± 13.0 and 19.6 ± 4.1 respectively (p 0.009). During RSV seasons the mean incidence rate ratio between groups was 1.82 (95% CI 1.60-2.08). Duration of hospitalization was 4.8 ± 7.0 and 3.9 ± 4.9 in late preterm and term infants, respectively (p 0.003). CONCLUSIONS: Late preterm-born infants (33-36 WGA) had a higher rate of hospitalization for overall and RSV bronchiolitis during the first year of life compared to those born at term.

Can CT imaging improve targeting accuracy in clip-based proton therapy of ocular melanoma?

To evaluate the benefit of adding CT imaging to the simulation process of clip-based proton therapy of ocular melanomas. For thirty ocular melanoma cases, the clip position in the eye model was determined based on orthogonal radiographs as well as on a CT image set. The geometrical shift of the clips between the standard simulation process and standard simulation process with addition of CT imaging (CT-guided) was determined. The dosimetric impact was evaluated by developing treatment plans based on both the standard-process model and the CT-guided model. In 40% of the studied cases, the difference in clip position between eye models created with and without CT was less than 0.5 mm. This difference was more than 1 mm in 17% of cases. The dosimetric impact of shifts below 1 mm was low because these shifts did not exceed the planning margins. For the four cases with a shift of more than 1 mm a reduction in target coverage (ΔV99%) of -3% to -6% was observed. Changes in macula and optic-disc mean dose of up to 16% and 35% of the prescribed dose were seen when these structures abutted the target. Adding CT imaging to the simulation process is beneficial in select cases where discrepancies between the eye model and ophthalmology measurements occur or where a critical structure is located close to the target and improved localization accuracy is wanted. For the majority of patients, addition of CT imaging does not result in quantifiable changes in dosimetry. Nevertheless, CT imaging is a valuable tool in the quality control of the modeling and treatment-planning process of clip-based eye treatments.

Impact of PCV7/PCV13 introduction on invasive pneumococcal disease (IPD) in young children: Comparison between meningitis and non-meningitis IPD.

BACKGROUND: The worldwide introduction of pneumococcal conjugate vaccines (PCV) into National Immunization Programs resulted in rapid and substantial reduction of invasive pneumococcal disease (IPD) rates in children. However, the reduction of meningitis vs. non-meningitis IPD (nm-IPD) was not yet fully elucidated. We compared 7-valent and 13-valent PCV (PCV7 and PCV13) impact on pneumococcal-meningitis vs. nm-IPD in Israeli children <5years. METHODS: We conducted an ongoing nationwide, prospective, population-based, active surveillance. PCV7 and PCV13 were implemented in Israel in July 2009 and November 2010, respectively. All pneumococcal isolates (blood and/or CSF) from IPD episodes in children <5years from July 2000 through June 2015 were included. Extrapolation for missing serotypes (34.7% of all isolates) was conducted. RESULTS: 4163 IPD cases were identified; 3739nm-IPD (89.8%) and 424 meningitis (10.2%). During the pre-PCV period (2000-2008), children <12months constituted 52.1% and 33.7% of meningitis and nm-IPD, respectively (p<0.001). The respective proportions of non-PCV13 serotypes (non-VT) were 18.2% vs. 10.1%, (p<0.001). Comparing the last study year (2014-2015) to the mean of pre-PCV period, meningitis incidence in children <5years decreased non-significantly by 27%, while nm-IPD decreased significantly by 69%. Dynamic rates of meningitis and nm-IPD caused by PCV13 serotypes were similar, with 93% and 95% overall reductions, respectively. However, non-VT increased in meningitis relatively to nm-IPD, mainly in children <24months. Serotype 12F rose sharply and significantly since 2009-2010 through 2014-2015 (28.6% of all non-VT meningitis in children <24m). CONCLUSIONS: The overall impact of PCV7/PCV13 in children <5years in Israel was less prominent in meningitis than in nm-IPD. This could be attributed to the younger age of children with meningitis and differences in causative serotypes between the two groups, as the decline of the incidence of meningitis and nm-IPD caused by vaccine-serotypes is similar. Continuous monitoring of meningitis and nm-IPD is warranted.

Dynamics of childhood invasive meningococcal disease in Israel during a 22-year period (1989-2010).

AIM: To describe the dynamics in the incidence of childhood invasive meningococcal disease (IMD) in Israel during a 22-year period (1989-2010). METHODS: A longitudinal prospective surveillance in all 27 medical centers with pediatric services in Israel. All cases of children <15 years old with positive blood/cerebrospinal fluid (CSF) culture for Neisseria meningitidis were reported. Demographic, clinical, and bacteriological data were recorded. Meningococcal vaccine was not routinely given to Israeli children during the study period. RESULTS: The mean age ± standard deviation (SD) among the 743 cases was 40.7 ± 40.2 months. The mean yearly incidence/100,000 was 2.0 ± 0.8. Age-specific incidences were 8.7 ± 2.8, 2.9 ± 1.5, and 0.8 ± 0.5 for children <1, 1-4, and >4 years old, respectively. The overall incidence decreased significantly from 3.7 in 1989 to 1.5 in 2010. Meningitis constituted 69.2 % of all cases. The most common serogroups were: B (76.9 %), C (10.9 %), Y (8.0 %), and W(135) (2.9 %). 78.6 % of all serogroup B isolates were from children <5 years old (p < 0.01). Serogroup C was found mainly in children ≥5 years old (63.4 %). The case fatality rates (CFRs) for children <1, 1-4, >4 years old, and the total study population were 9.2, 12.3, 7.7, and 9.9 %, respectively. CFRs were higher for children without meningitis (14.9 %) compared to children with meningitis (7.9 %) (p < 0.01). CONCLUSIONS: Overall, and for serogroups B and W135, childhood IMD rates decreased significantly in Israel during the study period, without routine vaccine usage. The most common serogroup in all age groups was B, which was most prevalent in children <5 years old. No change in the trend of the overall CFR was noted during the study period.

Beta-lactamase production by Kingella kingae in Israel is clonal and common in carriage organisms but rare among invasive strains.

The purpose of this study was to investigate the prevalence of ß-lactamase and the genomic clonality of a large collection of Kingella kingae isolates from Israeli patients with a variety of invasive infections and asymptomatic pharyngeal carriers. ß-lactamase production was studied by the nitrocefin method and the minimum inhibitory concentrations (MICs) of penicillin and amoxicillin-clavulanate were determined by the epsilon (Etest) method. The genotypic clonality of isolates was investigated by pulsed-field electrophoresis (PFGE). ß-lactamase was found in 2 of 190 (1.1 %) invasive isolates and in 66 of 429 (15.4 %) randomly chosen carriage organisms (p < 0.001). Overall, 73 distinct PFGE clones were identified (33 among invasive organisms and 56 among carriage isolates). ß-lactamase production was found to be limited to four distinct PFGE clones, which were common among carriage strains but rare among invasive strains, and all organisms in the collection belonging to these four clones expressed ß-lactamase. The penicillin MIC of ß-lactamase-producing isolates ranged between 0.094 and 2 mcg/mL (MIC50: 0.25 mcg/mL; MIC90: 1.5 mcg/mL) and that of amoxicillin-clavulanate between 0.064 and 0.47 mcg/mL (MIC50: 0.125 mcg/mL; MIC90: 0.125 mcg/mL). The penicillin MIC of ß-lactamase non-producing isolates ranged between <0.002 and 0.064 mcg/mL (MIC50: 0.023 mcg/mL; MIC90: 0.047 mcg/mL). Although ß-lactamase production is prevalent among K. kingae organisms carried by healthy carriers, the low invasive potential of most colonizing clones results in infrequent detection of the enzyme in isolates from patients with clinical infections. The exceptional presence of ß-lactamase among invasive organisms correlates with the favorable response of K. kingae infections to the administration of ß-lactamase-susceptible antibiotics.

Pneumococcal acute otitis media in infants and children in central Romania, 2009-2011: microbiological characteristics and potential coverage by pneumococcal conjugate vaccines.

OBJECTIVE: To assess the epidemiological and microbiological characteristics of pneumococcal acute otitis media (AOM) in children in Brasov, Central Romania, before the introduction of pneumococcal conjugate vaccine (PCV) into the routine national immunization program. METHODS: All AOM patients aged <5 years who underwent tympanocentesis or presented with purulent otorrhea of ≤24h duration during 2009-2011 were enrolled. RESULTS: Two hundred and twelve consecutive AOM patients had a middle ear fluid (MEF) culture performed; 99 (46.6%) episodes occurred in patients <12 months of age. One hundred and eleven (52.4%) episodes were culture-positive. Tympanocentesis was performed in 142 patients and spontaneous otorrhea cultures in 70 patients. Overall, 114 pathogens were recovered: Streptococcus pneumoniae was the most common isolate (81 isolates, 70.3% of all culture-positive episodes), followed by non-typeable Haemophilus influenzae (26, 20.7%), Streptococcus pyogenes (5, 4.5%), and Moraxella catarrhalis (2, 1.8%). Antibiotic susceptibility and serotyping were performed for 48 (59.3%) S. pneumoniae isolates: 45 (93.8%) were non-susceptible to penicillin (minimal inhibitory concentration (MIC) ≥2.0µg/ml in 24, 53.3%) and 37 (77.1%) isolates had ceftriaxone MIC values ≥0.5µg/ml (16 with MIC >2.0µg/ml). S. pneumoniae non-susceptibility rates to trimethoprim-sulfamethoxazole, erythromycin, and clindamycin were 75.0%, 58.3%, and 35.4%, respectively. All isolates were susceptible to chloramphenicol. Multidrug resistance was found in 33 (68.7%) isolates. The most common S. pneumoniae serotypes were 19F (14, 29.2%), 6B (8, 16.7%), 23F (8, 16.7%), and 14 (6, 12.5%). Serotype 19A was found in three (6.2%) patients and 6A in two (4.1%). Non-PCV13 serotypes represented six (12.6%) of all serotypes (four of them non-susceptible to penicillin). Thirty-six (75.0%) isolates were potentially covered by PCV7, 37 (77.0%) by PCV10, and 42 (87.5%) by PCV13. CONCLUSIONS: (1) S. pneumoniae was the most prevalent pathogen, with frequent antibiotic resistance and multi-resistance patterns; (2) most pneumococcal AOM and multidrug-resistant episodes could be prevented by PCVs.

Influence of age, social patterns and nasopharyngeal carriage on antibodies to three conserved pneumococcal surface proteins (PhtD, PcpA and PrtA) in healthy young children.

The acquisition of specific antibodies is paramount to protect children against pneumococcal diseases, and a better understanding of how age, ethnicity and/or Streptococcus pneumoniae (Spn) nasopharyngeal carriage influence the acquisition of antibodies to pneumococcal surface proteins (PSP) is important for the development of novel serodiagnostic and immunisation strategies. IgG antibody titres against three conserved PSP (PhtD, PcpA and PrtA) in the sera of 451 healthy children aged 1 to 24 months from Israel [Jewish (50.1 %) and Bedouin (49.9 %)] were measured by enzyme-linked immunosorbent assay (ELISA), while nasopharyngeal swabs from these children were assessed for the presence of Spn. Globally, anti-PhtD and anti-PrtA geometric mean concentrations (GMC; EU/ml) were high at <2.5 months of age [PhtD: 35.3, 95 % confidence interval (CI) 30.6-40.6; PrtA: 71.2, 95 % CI 60-84.5], was lower at 5-7 months of age (PhtD: 10, 95 % CI 8-12.4; PrtA: 17.9, 95 % CI 14.4-22.1) and only increased after 11 months of age. In contrast, an increase in anti-PcpA was observed at 5-7 months of age. Anti-PcpA and anti-PrtA, but not anti-PhtD, were significantly higher in Bedouin children (PcpA: 361.6 vs. 226.3, p = 0.02; PrtA: 67.2 vs. 29.5, p < 0.001) in whom Spn nasopharyngeal carriage was identified earlier (60 % vs. 38 % of carriers <6 months of age, p = 0.002). Spn carriage was associated with significantly higher anti-PSP concentrations in carriers than in non-carriers (p < 0.001 for each PSP). Thus, age, ethnicity and, essentially, nasopharyngeal carriage exert distinct cumulative influences on infant responses to PSP. These specific characteristics are worthwhile to include in the evaluation of pneumococcal seroresponses and the development of new PSP-based vaccines.

Rapid reduction in invasive pneumococcal disease after introduction of PCV7 into the National Immunization Plan in Israel.

BACKGROUND: The 7-valent conjugated vaccine (PCV7) was introduced into the Israeli National Immunization Program (NIP) in July 2009 (2, 4, 12 months schedule; 2 dose catch-up in second year of life). Nationwide active prospective surveillance on invasive pneumococcal disease (IPD) has been conducted in children since 1989. In the current study, IPD epidemiology in children <5 years during the 20 years before and 18 months after PCV7 NIP initiation, is reported. METHODS: All 27 centers performing blood/cerebrospinal fluid (CSF) cultures in children reported monthly IPD cases. Capture-recapture approach was used for completeness. RESULTS: During 1989-2010, 6022 IPD cases were reported in children <5 years; PCV7 serotypes (7VST) caused ∼50% of all episodes. In 2009 and 2010, 7VST IPD incidences <5 years of age (per 100,000) were 15.9 and 5.4, respectively (a 43% and 81% decrease, respectively) compared to 2003-2007 (mean incidence 27.8). Serotype 6A dynamics resembled those of 7VST. The respective overall IPD incidence decreases were 23% and 42%. The incidence dynamics of serotypes 1, 3, 5, 7F and 19A IPD were characterized by considerable fluctuations over the study period without any upwards or downwards trend in any of the age groups. The overall incidence of serotypes not included in the 13-valent pneumococcal conjugate vaccine (PCV13) did not vary significantly during the study period. By the end of 2010, 72% of the remaining IPD was caused by pneumococcal serotypes included in PCV13. CONCLUSIONS: An active prospective long-term surveillance, showed a rapid and sharp decline in IPD in children <5 years following initiation of NIP with PCV7. No serotype replacement has been observed so far. The transition from PCV7 to PCV13 initiated in October 2010 may lead to a further substantial decrease in IPD. Follow-up is needed to better determine the long-term PCV effects.

Failure to elicit seroresponses to pneumococcal surface proteins (pneumococcal histidine triad D, pneumococcal choline-binding protein A, and serine proteinase precursor A) in children with pneumococcal bacteraemia.

Pneumococcal surface proteins (PSPs) elicit antibody responses in infants and young children exposed to Streptococcus pneumoniae. These seroresponses could contribute to the aetiological diagnosis of pneumococcal disease, e.g. during the clinical development of novel PSP-based vaccines. In this study, we assessed the kinetics of antibody responses to three highly conserved and immunogenic PSPs (pneumococcal histidine triad D (PhtD), pneumococcal choline-binding protein A (PcpA), and serine proteinase precursor A (PrtA)) in 106 children (median age, 21.3 months; males, 58.5%) admitted for pneumococcal bacteraemia. Anti-PhtD, anti-PcpA and anti-PrtA antibodies were measured by ELISA, and compared in 61 pairs of acute (≤7 days) and convalescent (>14 days of admission) serum samples. Acute serum titres were similar to those observed in healthy children, and were unaffected by the acid dissociation of circulating immune complexes. Despite proven bacteraemia, seroresponses (≥2-fold increase in anti-PSP antibody concentrations) were only identified in 31 of 61 children (50.8%), directed against PrtA (n = 23, 37.7%), PcpA (n = 19, 31.1%), and PhtD (n = 16, 26.2%), or several PSPs (two PSPs, n = 13, 21.3%; three PSPs, n = 7, 11.5%). Certain seroresponses were very strong (maximal fold-increases: PhtD, 26; PcpA, 72; PrtA, 12). However, anti-PSP antibody concentrations failed to increase in the convalescent sera of 30 of 61 (49.2%) bacteraemic children, and even declined (≥2 fold) in 13 of 61 (21.3%), mostly infants aged <6 months (8/13, 61.5%), possibly through consumption of maternal antibodies. Thus, pneumococcal bacteraemia may fail to elicit antibody responses, and may even have an antibody-depleting effect in infants. This novel observation identifies an important limitation of serology-based studies for the identification of bacteraemic children.

Transmission of Streptococcus pneumoniae in adults may occur through saliva.

Of 742 army recruits tested for pneumococcal nasopharyngeal/oropharyngeal carriage, 6·6% were positive. Frequent sharing of a drinking glass/bottle was a common, strong and independent risk factor for pneumococcal carriage. Our findings strongly suggest, for the first time, that in young adults, transmission of pneumococci may occur via saliva and this should be considered when conducting an outbreak investigation and carriage studies.

Hepatitis A disease following the implementation of universal vaccination: who is at risk?

The incidence of acute hepatitis A in Israel has decreased 25 folds in less than a decade, following the introduction of a two-dose universal toddler's hepatitis A immunization in July 1999. This retrospective study describes demographic data and behavioural determinants of hepatitis A patients following the implementation of a vaccination programme. All records of hepatitis A patients reported to the Ministry of Health during the years 2003 through 2005 were reviewed, and an epidemiological investigation was conducted. During the study period, 420 hepatitis A patients were reported, representing an average annual incidence of two per 100,000 population. Case fatality rate was 0.5%. The majority of the patients were younger than 15 years of age, males and non-Jewish. The highest incidence was recorded in east Jerusalem, where vaccine coverage is relatively low. After exclusion of 165 east Jerusalem patients, 133 (52.2%) patients were available for an interview. Of those, 16 (6%) had possible occupational exposure, 37 (27.8%) travelled to endemic areas, 44 (17%) were contacts of hepatitis A cases, and 3 male patients had sex with men. No known risk determinant was identified in 33 (24.8%) patients. Four patients (3%) were previously immunized with one dose, and none had two doses. The introduction of universal toddler hepatitis A vaccination decreased morbidity. Most of the patients who were detected 4-6 years after the implementation of the vaccination programme could be classified into one of the known risk groups for hepatitis A infection or living in a partly vaccinated community.

Prevalence of pilus-encoding islets among acute otitis media Streptococcus pneumoniae isolates from Israel.

We evaluated the distribution of the two known Streptococcus pneumoniae pilus encoding islets (PI-1 and PI-2) among a panel of 113 acute otitis media clinical isolates from Israel. PI-1 was present in 30.1% (n = 34) of the isolates tested, and PI-2 was present in 7% (n = 8). In addition, we found that: (i) the PI positive isolates, 50% of which belong to the international clones Spain(9V)-3 (ST156) and Taiwan(19F)-14 (ST236), correlate with the genotype (as determined by multilocus sequence typing) but not with the serotype; (ii) PI-2 was not present in the absence of Pl-1; and (iii) the frequency of PI-1 was higher among antibiotic-resistant isolates.

Haemophilus influenzae serotype b conjugate vaccine failure in twelve countries with established national childhood immunization programmes.

The present study describes the clinical and immunological features of children with Hib vaccine failure, who were identified through national surveillance between 1996 and 2001 in Europe, Israel and Australia. True vaccine failure was defined as invasive Hib disease occurring ≥2 weeks after one dose, given after the first birthday, or ≥1 week after ≥2 doses, given at <1 year of age. Of the 423 cases (representing 0.2 cases per 100,000 child-years at risk) reported, 330 (78%) had received three doses in the first year of life and developed disease at a median age of 28 months. Of the remaining 93, 48 had received two doses in infancy, 34 had received four doses including a booster, and 11 had received a single dose after 12 months of age. These children developed disease at a median age of 12, 33 and 71 months, respectively. In total, 47 out of 258 children (18%) with available information had an underlying medical problem (including prematurity) and 53 out of 161 (33%) had immunoglobulin deficiency. Convalescent Hib antibody concentrations were above the putative protective concentration of 1.0 mg/L in 147/194 (76%) children; low concentrations were associated with both the presence of an underlying medical problem and young age at the time of Hib disease. Almost all children who received an additional vaccine dose developed antibodies at protective concentrations. Thus, Hib vaccine failure is rare, but can occur with any immunization schedule. Children with Hib vaccine failure should have immunoglobulin and convalescent Hib antibody concentrations measured after infection and receive additional vaccination, if required.

Risk factors for the initial symptomatic giardia infection in a cohort of young Arab-Bedouin children.

BACKGROUND: Giardiasis is a common protozoan infection with clinical manifestations in children ranging from asymptomatic carriage to persistent diarrhoea with malabsorption. It can lead to growth and developmental retardation. AIM: The study evaluated risk factors for the initial symptomatic giardiasis (SG) episode among Arab-Bedouin children in Israel. METHODS: A community-based, prospective cohort study was conducted in Rahat, a Bedouin township in southern Israel. Infants (n=238) were followed by weekly visits from birth to age 18 months. Giardia infection was identified by antigen detection in faecal specimens. RESULTS: Approximately 26% of children experienced one or more SG episode. Mean (SD) age for first SG episode was 12.3 (3.3) months, with 95% of episodes occurring in children >6 months of age. Risk for the first SG in children >6 months of age was associated with it being spring or summer [odds ratio (OR) 6.16, p<0.001], exposure to livestock (OR 4.89, p=0.002) and prior infection with entero-aggregative Escherichia coli (EAEC) (OR 1.12 for each additional percentage in stool prevalence, p=0.02). Weight-for-age Z-scores at age 6 months were inversely related to SG risk (OR 0.62 for each unit increase in Z-score, p=0.029). CONCLUSIONS: Giardiasis is an important cause of diarrhoea in Bedouin children. Increased risk of SG in spring/summer might be linked to environmental conditions or seasonal dietary practices which increase virulence or transmission. SG in those exposed to livestock suggests that there are zoonotic risk factors or that hygiene is a causal factor. The association between EAEC infection and SG warrants further investigation.

Estimating the direct impact of new conjugate vaccines against invasive pneumococcal disease.

New pneumococcal conjugate vaccines (PCVs) are now becoming available. These formulations differ from the heptavalent diphtheria toxin variant conjugate vaccine (7vCRM, Prevenar/Prevnar) both in the number of serotypes and in serotype-specific immunogenicity. This review proposes an algorithm that attempts to predict the overall impact of these differences in vaccine formulation and immunogenicity on invasive pneumococcal disease (IPD) effectiveness. It builds on the principles underlying WHO licensure criteria for new PCVs, that serotype-specific anti-polysaccharide immunogenicity is potentially predictive of effectiveness. The algorithm used three sources of information: serotype-specific effectiveness data for 7vCRM, serotype-specific head-to-head immunogenicity data with 7vCRM and a recently licensed 10-valent pneumococcal non-typeable H. influenzae protein D-conjugate vaccine (PHiD-CV, Synflorix), and epidemiological information regarding the serotypes causing IPD in young children. Based on this algorithm, PHiD-CV and 7vCRM are predicted to prevent approximately 60-80% and 45-80%, respectively of IPD in young children worldwide, with significant variability by country and region.

Impact of pneumococcal conjugate vaccine on infections caused by antibiotic-resistant Streptococcus pneumoniae.

Studies have shown that vaccination with seven-valent pneumococcal conjugate vaccine (PCV7) results in a decline in nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae, in carriage of vaccine-type pneumococci, and in replacement by non-vaccine serotypes. Vaccines can reduce pneumococcal resistance in vaccinated and unvaccinated populations by reducing the carriage of antibiotic-resistant serotypes, which protects the vaccinated population and prevents spread of disease to others, and by decreasing antibiotic resistance through overall reduction in antibiotic use. However, while reducing the level of vaccine serotypes and drug-resistant serotypes in the nasopharynx, PCV7 also causes non-vaccine pneumococci replacement. The impact of serotype replacement on disease is not clearly understood. Pelton et al. surveyed two communities shortly after the introduction of the PCV7 immunization programme and found that while colonization with vaccine serotypes declined from 22% to 2% from 2000 to 2003, prevalence of non-vaccine serotypes increased from 7% to 16%. Although penicillin-resistant colonizing S. pneumoniae isolates initially declined, penicillin-intermediate isolates increased 2 years following PCV7 introduction. The change was primarily accounted for by an increase in penicillin-intermediate serotype 19A. Serotype 19A is the only serotype not affected by PCV7 that is prevalent worldwide, clinically important, and highly multidrug-resistant. A study by Hicks et al. established serotype 19A as the predominant post-PCV7 cause of invasive pneumococcal disease (IPD) in children and the elderly. An increase in IPD rates caused by antibiotic-resistant serotype 19A isolates can also occur without vaccination; reports indicate increases in regions characterized by extensive antibiotic use, underscoring the importance of strategies to contain antibiotic resistance.

Clinical/otologic score before and during treatment of acute otitis media.

OBJECTIVES: To determine clinical characteristics of AOM at presentation and during therapy according to specific etiologies. PATIENTS AND METHODS: 1003 patients studied during 1996-2001 in antibiotic efficacy studies underwent tympanocentesis and middle ear fluid culture at enrollment and on Day 4-6 (in initially culture-positive patients only). We used a clinical/otologic (CO) score for evaluating severity of fever, irritability and tympanic membrane redness and bulging (0-3 each parameter, maximal score=12). RESULTS: Seven hundred sixty-three patients had positive cultures with 392 (39%) Haemophilus influenzae, 198 (20%) Streptococcus pneumoniae and 173 (17%) mixed H. influenzae and S. pneumoniae infection. Mean CO score was higher in culture-positive versus culture-negative patients (8.21+/-2.17 vs. 7.73+/-2.32, p=0.003) regardless of isolated organism. A marked improvement in CO score was observed on Day 4-6 in all patients: 1.83+/-2.18 in children initially culture-positive and 0.9+/-1.67 in those initially culture-negative (p<0.001). The improvement was greater in patients with eradication versus those with bacteriological failure (CO score 1.52+/-1.82 vs. 2.77+/-2.85, p<0.001). CONCLUSIONS: CO score before treatment, after bacterial eradication or in bacteriologic failures are similar in bacterial AOM and are not predictive of the etiology of the disease.

Socioeconomic correlates of antibody levels to enteric pathogens among Israeli adolescents.

We examined the association between socioeconomic status and the level of serum antibodies to selected faeco-orally transmitted pathogens among Israeli adolescents. Random samples of eighty volunteers aged 12-15 years from high (HSL), medium (MSL) and low (LSL) standard of living towns were included in the study. Serum samples were examined by radioimmunoassay for HAV and by in-house-developed ELISA systems for IgA and IgG antibody levels against Shigella sonnei, S. flexneri, E. coli O157:H7 lipopolysacchride and Cryptosporidium parvum antigens. Seropositivity to HAV was highest (98.8%) in the LSL towns and lowest (25%) in the HSL towns, showing a statistically significant linear trend. Antibody levels to the other enteropathogens had gender variation, with higher titres in females. Significantly lower titres in the HSL towns were found for: IgA anti-S. sonnei in females (P<0.001); IgG anti-S. sonnei in females (P=0.024) and males (P=0.033); IgG anti-S. flexneri in females (P=0.016). Inverse linear association with socioeconomic status was found for IgA anti-C. parvum in females (P<0.001); IgA anti-E. coli O157:H7 in females (P<0.001) and males (P=0.024). A statistically significant association between HAV seropositivity and higher titres of IgA anti-S. sonnei and E. coli O157:H7 was shown. In conclusion, exposure to enteropathogens transmitted via the faecal-oral route in communities of lower socioeconomic status is reflected in a higher prevalence of lifelong lasting antibodies to HAV, and higher levels of antibodies to bacterial and protozoan enteropathogens. Among females, the levels of specific serum antibodies are higher and more strongly associated with low socioeconomic status.