Epidemiology of nasopharyngeal carriage of respiratory bacterial pathogens in children and adults: cross-sectional surveys in a population with high rates of pneumococcal disease

<p>Abstract</p> <p>Background</p> <p>To determine the prevalence of carriage of respiratory bacterial pathogens, and the risk factors for and serotype distribution of pneumococcal carriage in an Australian Aboriginal population.</p> <p>Methods</p> <p>Surveys of nasopharyngeal carriage of <it>Streptococcus pneumoniae</it>, non-typeable <it>Haemophilus influenzae</it>, and <it>Moraxella catarrhalis </it>were conducted among adults (≥16 years) and children (2 to 15 years) in four rural communities in 2002 and 2004. Infant seven-valent pneumococcal conjugate vaccine (7PCV) with booster 23-valent pneumococcal polysaccharide vaccine was introduced in 2001. Standard microbiological methods were used.</p> <p>Results</p> <p>At the time of the 2002 survey, 94% of eligible children had received catch-up pneumococcal vaccination. 324 adults (538 examinations) and 218 children (350 examinations) were enrolled. Pneumococcal carriage prevalence was 26% (95% CI, 22-30) among adults and 67% (95% CI, 62-72) among children. Carriage of non-typeable <it>H. influenzae </it>among adults and children was 23% (95% CI, 19-27) and 57% (95% CI, 52-63) respectively and for <it>M. catarrhalis</it>, 17% (95% CI, 14-21) and 74% (95% CI, 69-78) respectively. Adult pneumococcal carriage was associated with increasing age (p = 0.0005 test of trend), concurrent carriage of non-typeable <it>H. influenzae </it>(Odds ratio [OR] 6.74; 95% CI, 4.06-11.2) or <it>M. catarrhalis </it>(OR 3.27; 95% CI, 1.97-5.45), male sex (OR 2.21; 95% CI, 1.31-3.73), rhinorrhoea (OR 1.66; 95% CI, 1.05-2.64), and frequent exposure to outside fires (OR 6.89; 95% CI, 1.87-25.4). Among children, pneumococcal carriage was associated with decreasing age (p < 0.0001 test of trend), and carriage of non-typeable <it>H. influenzae </it>(OR 9.34; 95% CI, 4.71-18.5) or <it>M. catarrhalis </it>(OR 2.67; 95% CI, 1.34-5.33). Excluding an outbreak of serotype 1 in children, the percentages of serotypes included in 7, 10, and 13PCV were 23%, 23%, and 29% (adults) and 22%, 24%, and 40% (2-15 years). Dominance of serotype 16F, and persistent 19F and 6B carriage three years after initiation of 7PCV is noteworthy.</p> <p>Conclusions</p> <p>Population-based carriage of <it>S. pneumoniae</it>, non-typeable <it>H. influenzae</it>, and <it>M. catarrhalis </it>was high in this Australian Aboriginal population. Reducing smoke exposure may reduce pneumococcal carriage. The indirect effects of 10 or 13PCV, above those of 7PCV, among adults in this population may be limited.</p

Compared to placebo, long-term antibiotics resolve otitis media with effusion (OME) and prevent acute otitis media with perforation (AOMwiP) in a high-risk population: A randomized controlled trial

© 2008 Leach et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background : For children at high risk of chronic suppurative otitis media (CSOM), strategies to prevent acute otitis media with perforation (AOMwiP) may reduce progression to CSOM. Methods : In a double blind study in northern Australia, 103 Aboriginal infants with first detection of OME were randomised to receive either amoxicillin (50 mg/kg/d BD) or placebo for 24 weeks, or until bilateral aerated middle ears were diagnosed at two successive monthly examinations (success). Standardised clinical assessments and international standards for microbiology were used. Results : Five of 52 infants in the amoxicillin group and none of 51 infants in the placebo group achieved success at the end of therapy (Risk Difference = 9.6% [95% confidence interval 1.6,17.6]). Amoxicillin significantly reduced the proportion of children with i) perforation at the end of therapy (27% to 12% RD = -16% [-31,-1]), ii) recurrent perforation during therapy (18% to 4% RD = -14% [-25,-2]), and iii) reduced the proportion of examinations with a diagnosis of perforation during therapy (20% to 8% adjusted risk ratio 0.36 [0.15,0.83] p = 0.017). During therapy, the proportion of examinations with penicillin non-susceptible (MIC > 0.1 microg/ml) pneumococci was not significantly different between the amoxicillin group (34%) and the placebo group (40%). Beta-lactamase positive non-capsular H. influenzae (NCHi) were uncommon during therapy but more frequent in the amoxicillin group (10%) than placebo (5%). Conclusion : Aboriginal infants receiving continuous amoxicillin had more normal ears, fewer perforations, and less pneumococcal carriage. There was no statistically significant increase in resistant pneumococci or NCHi in amoxicillin children compared to placebo children who received regular paediatric care and antibiotic treatment for symptomatic illnesses

Corticosteroid injection for tennis elbow or lateral epicondylitis: a review of the literature

Lateral epicondylitis or tennis elbow is a painful and functionally limiting entity affecting the upperextremity and is frequently treated by hand surgeons. Corticosteroid injection is one of the most common interventions for lateral epicondylitis or tennis elbow. Here, a review of the medical literature on this treatment is presented

Repeatability and sensitivity of T2* measurements in patients with head and neck squamous cell carcinoma at 3T.

Purpose To determine whether quantitation of T2* is sufficiently repeatable and sensitive to detect clinically relevant oxygenation levels in head and neck squamous cell carcinoma (HNSCC) at 3T.Materials and methods Ten patients with newly diagnosed locally advanced HNSCC underwent two magnetic resonance imaging (MRI) scans between 24 and 168 hours apart prior to chemoradiotherapy treatment. A multiple gradient echo sequence was used to calculate T2* maps. A quadratic function was used to model the blood transverse relaxation rate as a function of blood oxygenation. A set of published coefficients measured at 3T were incorporated to account for tissue hematocrit levels and used to plot the dependence of fractional blood oxygenation (Y) on T2* values, together with the corresponding repeatability range. Repeatability of T2* using Bland-Altman analysis, and calculation of limits of agreement (LoA), was used to assess the sensitivity, defined as the minimum difference in fractional blood oxygenation that can be confidently detected.Results T2* LoA for 22 outlined tumor volumes were 13%. The T2* dependence of fractional blood oxygenation increases monotonically, resulting in increasing sensitivity of the method with increasing blood oxygenation. For fractional blood oxygenation values above 0.11, changes in T2* were sufficient to detect differences in blood oxygenation greater than 10% (Δ T2* > LoA for ΔY > 0.1).Conclusion Quantitation of T2* at 3T can detect clinically relevant changes in tumor oxygenation within a wide range of blood volumes and oxygen tensions, including levels reported in HNSCC. J. Magn. Reson. Imaging 2016;44:72-80

Inhibition of tyrosine kinase receptors by SU6668 promotes abnormal stromal development at the periphery of carcinomas

Dynamic contrast-enhanced (albumin-Gd-DTPA) magnetic resonance imaging, performed during 2 weeks of daily administration of an inhibitor of tyrosine kinase receptors (SU6668) in an HT-29 colon carcinoma model, revealed the onset of a hyper-enhancing rim, not observed in untreated tumours. To account for tissue heterogeneity in the quantitative analysis, we segmented tumours into three subunits automatically identified by cluster analysis of the enhancement curves using a k-means algorithm. Transendothelial permeability (Kps) and fractional plasma volume (fPV) were calculated in each subunit. An avascular and necrotic region, an intermediate zone and a well-vascularised periphery were reliably identified. During untreated tumour growth, the identified sub-regions did not substantially change their enhancement pattern. Treatment with SU6668 induced major changes at tumour periphery where a significant increase of Kps and fPV was observed with respect to control tumours. Histology revealed a sub-capsular layer composed of hyper-dense viable tumour cells in the periphery of untreated tumours. The rim of viable neoplastic cells was reduced in treated tumours, and replaced by loose connective tissue characterised by numerous vessels, which explains the observed hyper-enhancement. The present data show a peripheral abnormal development of cancer-associated stroma, indicative of an adaptive response to anti-angiogenic treatment

Area-level deprivation and adiposity in children: is the relationship linear?

OBJECTIVE: It has been suggested that childhood obesity is inversely associated with deprivation, such that the prevalence is higher in more deprived groups. However, comparatively few studies actually use an area-level measure of deprivation, limiting the scope to assess trends in the association with obesity for this indicator. Furthermore, most assume a linear relationship. Therefore, the aim of this study was to investigate associations between area-level deprivation and three measures of adiposity in children: body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). DESIGN: This is a cross-sectional study in which data were collected on three occasions a year apart (2005-2007). SUBJECTS: Data were available for 13,333 children, typically aged 11-12 years, from 37 schools and 542 lower super-output areas (LSOAs). MEASURES: Stature, mass and WC. Obesity was defined as a BMI and WC exceeding the 95th centile according to British reference data. WHtR exceeding 0.5 defined obesity. The Index of Multiple Deprivation affecting children (IDACI) was used to determine area-level deprivation. RESULTS: Considerable differences in the prevalence of obesity exist between the three different measures. However, for all measures of adiposity the highest probability of being classified as obese is in the middle of the IDACI range. This relationship is more marked in girls, such that the probability of being obese for girls living in areas at the two extremes of deprivation is around half that at the peak, occurring in the middle. CONCLUSION: These data confirm the high prevalence of obesity in children and suggest that the relationship between obesity and residential area-level deprivation is not linear. This is contrary to the 'deprivation theory' and questions the current understanding and interpretation of the relationship between obesity and deprivation in children. These results could help make informed decisions at the local level

Measuring nasal bacterial load and its association with otitis media

BACKGROUND: Nasal colonisation with otitis media (OM) pathogens, particularly Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, is a precursor to the onset of OM. Many children experience asymptomatic nasal carriage of these pathogens whereas others will progress to otitis media with effusion (OME) or suppurative OM. We observed a disparity in the prevalence of suppurative OM between Aboriginal children living in remote communities and non-Aboriginal children attending child-care centres; up to 60% and <1%, respectively. This could not be explained by the less dramatic difference in rates of carriage of respiratory bacterial pathogens (80% vs 50%, respectively). In this study, we measured nasal bacterial load to help explain the different propensity for suppurative OM in these two populations. METHODS: Quantitative measures (colony counts and real-time quantitative PCR) of the respiratory pathogens S. pneumoniae, H. influenzae and M. catarrhalis, and total bacterial load were analysed in nasal swabs from Aboriginal children from remote communities, and non-Aboriginal children attending urban child-care centres. RESULTS: In both populations nearly all swabs were positive for at least one of these respiratory pathogens. Using either quantification method, positive correlations between bacterial load and ear state (no OM, OME, or suppurative OM) were observed. This relationship held for single and combined bacterial respiratory pathogens, total bacterial load, and the proportion of respiratory pathogens to total bacterial load. Comparison of Aboriginal and non-Aboriginal children, all with a diagnosis of OME, demonstrated significantly higher loads of S. pneumoniae and M. catarrhalis in the Aboriginal group. The increased bacterial load despite similar clinical condition may predict persistence of middle ear effusions and progression to suppurative OM in the Aboriginal population. Our data also demonstrated the presence of PCR-detectable non-cultivable respiratory pathogens in 36% of nasal swabs. This may have implications for the pathogenesis of OM including persistence of infection despite aggressive therapies. CONCLUSION: Nasal bacterial load was significantly higher among Aboriginal children and may explain their increased risk of suppurative OM. It was also positively correlated with ear state. We believe that a reduction in bacterial load in high-risk populations may be required before dramatic reductions in OM can be achieved

Dynamics of pneumococcal nasopharyngeal carriage in healthy children attending a day care center in northern Spain. influence of detection techniques on the results

<p>Abstract</p> <p>Background</p> <p>Pneumococcal nasopharyngeal carriage precedes invasive infection and is the source for dissemination of the disease. Differences in sampling methodology, isolation or identification techniques, as well as the period (pre -or post-vaccination) when the study was performed, can influence the reported rates of colonization and the distribution of serotypes carried.</p> <p>Objectives</p> <p>To evaluate the prevalence and dynamics of pneumococcal nasopharyngeal colonization in healthy children aged 6-34 months attending a day care center with a high level of hygiene and no overcrowding. The study was performed 3-4 years after the 7-valent pneumococcal vaccine was introduced, using multiple methodologies to detect and characterize the isolates.</p> <p>Methods</p> <p>Over 12 months, 25 children were sampled three times, 53 children twice and 27 children once. Three <it>Streptococcus pneumoniae </it>typing techniques were used: Quellung, Pneumotest-Latex-kit and multiplex-polymerase chain reaction (PCR). The similarity of isolates of the same serotype was established by pulsed field gel electrophoresis (PFGE) and occasionally the multilocus sequence type (ST) was also determined.</p> <p>Results</p> <p>Overall pneumococcal carriage and multiple colonization rates were 89.5% (94/105) and 39%, respectively. Among 218 pneumococci detected, 21 different serotypes and 13 non-typeable isolates were found. The most prevalent serotypes were 19A, 16F and 15B. Serotypes 15B, 19A and 21 were mainly found as single carriage; in contrast serotypes 6B, 11A and 20, as well as infrequent serotypes, were isolated mainly as part of multiple carriage. Most 19A isolates were ST193 but most serotypes showed high genetic heterogeneity. Changes in the pneumococci colonizing each child were frequent and the same serotype detected on two occasions frequently showed a different genotype. By multiplex-PCR, 100% of pneumococci could be detected and 94% could be serotyped versus 80.3% by the Quellung reaction and Pneumotest-Latex in combination (p < 0.001).</p> <p>Conclusions</p> <p>Rates of <it>S. pneumoniae </it>carriage and multiple colonization were very high. Prevalent serotypes differed from those found in similar studies in the pre-vaccination period. In the same child, clearance of a pneumococcal strain and acquisition of a new one was frequent in a short period of time. The most effective technique for detecting pneumococcal nasopharyngeal carriers was multiplex-PCR.</p

A Longitudinal Study of Streptococcus pneumoniae Carriage in a Cohort of Infants and Their Mothers on the Thailand-Myanmar Border

Background Pneumococcal disease is a major cause of childhood death. Almost a third of the world's children live in Southeast Asia, but there are few data from the region on pneumococcal colonization or disease. Our aim was to document the dynamics of pneumococcal carriage in a rural SE Asian birth cohort. Methods We studied 234 Karen mother-infant pairs in Northwestern Thailand. Infants were followed from birth and nasopharyngeal swabs were taken from mother and infant at monthly intervals until 24 months old. Results 8,386 swabs were cultured and 4,396 pneumococci characterized. Infants became colonized early (median 45.5 days; 95% confidence interval [CI] 44.5-46.0) and by 24 months had a median of seven (range 0–15) carriage episodes. Maternal smoking and young children in the house were associated with earlier colonization (hazard ratio [HR] 1.5 (95% CI 1.1–2.1) and 1.4 (95% CI 1.0–1.9)). For the four commonest serotypes and non-typeable pneumococci, previous exposure to homologous or heterologous serotypes resulted in an extended interval to reacquisition of the same serotype. Previous colonization by serotypes 14 and 19F was also associated with reduced carriage duration if subsequently reacquired (HR [first reacquisition] 4.1 (95% CI 1.4–12.6) and 2.6 (1.5–4.7)). Mothers acquired pneumococci less frequently, and carried them for shorter periods, than infants (acquisition rate 0.5 vs. 1.1 /100 person-days, p<0.001; median duration 31.0 vs. 60.5 days, p = 0.001). 55.8% of pneumococci from infants were vaccine serotypes (13-valent pneumococcal conjugate vaccine, PCV13), compared with 27.5% from mothers (p<0.001). Non-typeable pneumococcal carriage was common, being carried at least once by 55.1% of infants and 32.0% of mothers. Conclusions Pneumococcal carriage frequency and duration are influenced by previous exposure to both homologous and heterologous serotypes. These data will inform vaccination strategies in this population

Immuno-Therapy with Anti-CTLA4 Antibodies in Tolerized and Non-Tolerized Mouse Tumor Models

Monoclonal antibodies specific for cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA4) are a novel form of cancer immunotherapy. While preclinical studies in mouse tumor models have shown anti-tumor efficacy of anti-CTLA4 injection or expression, anti-CTLA4 treatment in patients with advanced cancers had disappointing therapeutic benefit. These discrepancies have to be addressed in more adequate pre-clinical models. We employed two tumor models. The first model is based on C57Bl/6 mice and syngeneic TC-1 tumors expressing HPV16 E6/E7. In this model, the HPV antigens are neo-antigens, against which no central tolerance exists. The second model involves mice transgenic for the proto-oncogen neu and syngeneic mouse mammary carcinoma (MMC) cells. In this model tolerance to Neu involves both central and peripheral mechanisms. Anti-CTLA4 delivery as a protein or expression from gene-modified tumor cells were therapeutically efficacious in the non-tolerized TC-1 tumor model, but had no effect in the MMC-model. We also used the two tumor models to test an immuno-gene therapy approach for anti-CTLA4. Recently, we used an approach based on hematopoietic stem cells (HSC) to deliver the relaxin gene to tumors and showed that this approach facilitates pre-existing anti-tumor T-cells to control tumor growth in the MMC tumor model. However, unexpectedly, when used for anti-CTLA4 gene delivery in this study, the HSC-based approach was therapeutically detrimental in both the TC-1 and MMC models. Anti-CTLA4 expression in these models resulted in an increase in the number of intratumoral CD1d+ NKT cells and in the expression of TGF-β1. At the same time, levels of pro-inflammatory cytokines and chemokines, which potentially can support anti-tumor T-cell responses, were lower in tumors of mice that received anti-CTLA4-HSC therapy. The differences in outcomes between the tolerized and non-tolerized models also provide a potential explanation for the low efficacy of CTLA4 blockage approaches in cancer immunotherapy trials