Interpreting Seroepidemiologic Studies of Influenza in a Context of Nonbracketing Sera

Background: In influenza epidemiology, analysis of paired sera collected from people before and after influenza seasons has been used for decades to study the cumulative incidence of influenza virus infections in populations. However, interpretation becomes challenging when sera are collected after the start or before the end of an epidemic, and do not neatly bracket the epidemic. Methods: Serum samples were collected longitudinally in a community-based study. Most participants provided their first serum after the start of circulation of influenza A(H1N1)pdm09 virus in 2009. We developed a Bayesian hierarchical model to correct for nonbracketing sera and estimate the cumulative incidence of infection from the serological data and surveillance data in Hong Kong. Results: We analyzed 4,843 sera from 2,097 unvaccinated participants in the study, collected from April 2009 to December 2010. After accounting for nonbracketing, we estimated that the cumulative incidence of H1N1pdm09 virus infection was 45% (95% credible interval [CI] = 40%, 49%), 17% (95% CI = 13%, 20%), and 11% (95% CI = 6%, 18%) for children ages 0–18 years, adults 19–50 years, and older adults >50 years, respectively. Including all available data substantially increased precision compared with a simpler analysis based only on sera collected at 6-month intervals in a subset of participants. Conclusions: We developed a framework for the analysis of antibody titers that accounted for the timing of sera collection with respect to influenza activity and permitted robust estimation of the cumulative incidence of infection during an epidemic.postprin

Variability in the immunogenicity of inactivated seasonal influenza vaccine in children due to age and recent previous influenza vaccination

Poster Session: VaccinesBackground: Annual receipt of trivalent inactivated influenza (TIV) vaccination is recommended for school-age children in some countries. However, there is little data on the variability of the immunogenicity of influenza vaccination in children and how this is affected by their age and recent influenza vaccination history. Materials and Methods: We used data on children in a Hong Kong community-based study who were randomized to receive TIV before the 2009-2010 influenza season. Antibody titers against seasonal and pandemic A(H1N1), seasonal A(H3N2), and two B influenza viruses (B/Brisbane and B/Florida) were measured by hemagglutination inhibition immediately before and 1 month after vaccination (Cowling et al. Clin Infect Dis. 2012). Multivariate regression models were fitted in a Bayesian framework to characterize the distribution of changes in antibody titers following vaccination and update previous findings by considering the correlation between virus strains (Ng et al. Pediatr Infect Dis J. 2013). Results: In 452 subjects, statistically significant rises in the geometric means of all antibody titers were observed, with those against the virus strains included in the TIV rising by geometric means of 7.95 to 13.36; those against pandemic A(H1N1) and B/Florida rose by 1.47 and 4.21, respectively. Geometric standard deviations were between 3.76 and 8.41 around the geometric means, with pandemic A(H1N1) showing the least variability in rises. The most closely correlated titer increases were those for the two influenza B viruses, while increases in pandemic A(H1N1) titers were unrelated to any other titer. Being vaccinated in either of the two previous years significantly reduced the increase in seasonal A(H1N1) and A(H3N2) antibody titers, while among children not vaccinated in the previous 2 years, those aged > 9 years experienced significantly higher increases in the influenza B titers than those aged 6-8 years. Conclusions: Increases in antibody titers following vaccination can vary depending on age and vaccination history. Results from our study suggest that humoral antibody response to TIV may be lower in children receiving repeated vaccination, but receipt of TIV induced seroprotection in most subjects.published_or_final_versio

Determinants of serum 25-hydroxyvitamin D in Hong Kong

Vitamin D plays an important role in skeletal health throughout life. Some studies have hypothesised that vitamin D may reduce the risk of other diseases. Our study aimed to estimate age-specific and sex-specific serum 25-hydroxyvitamin D (25(OH)D) status and to identify the determinants of serum 25(OH)D status in Hong Kong, a subtropical city in southern China. In 2009-2010, households in Hong Kong were followed up to identify acute respiratory illnesses, and sera from 2694 subjects were collected in three to four different study phases to permit measurement of 25(OH)D levels at different times of the year. A questionnaire survey on diet and lifestyle was conducted among children, with simultaneous serum collection in April and May 2010. The mean of serum 25(OH)D levels in age groups ranged from 39 to 63 nmol/l throughout the year with the mean values in all age groups in spring below 50 nmol/l. Children aged 6-17 years, and girls and women had significantly lower serum 25(OH)D levels than adults, and boys and men, respectively (all P< 0·001). We estimated that serum 25(OH)D levels in Hong Kong followed a lagged pattern relative to climatic season by 5 weeks with lowest observed levels in early spring (March). For children aged 6-17 years, reporting a suntan, having at least 1 servings of fish/week and having at least 1 serving of eggs/week were independently associated with higher serum 25(OH)D levels. Adequate sunlight exposure and increased intake of dietary vitamin D could improve vitamin D status, especially for children and females in the winter and spring.postprin

Inferring Influenza Infection Attack Rate from Seroprevalence Data

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A longitudinal study of infection attack rates among hospital outpatients in Hong Kong during the epidemic of the human swine influenza A/H1N1 virus in 2009 by tracking temporal changes in age-specific seroprevalence rates

Poster Presentations: Emerging / Infectious Diseases: abstract no. P110-Ab0092Conference Theme: Translating Health Research into Policy and Practice for Health of the Populationpublished_or_final_versio

Training simulated patients: evaluation of a training approach using self-assessment and peer/tutor feedback to improve performance

<p>Abstract</p> <p>Background</p> <p>Most medical schools use simulated patients (SPs) for teaching. In this context the authenticity of role play and quality of feedback provided by SPs is of paramount importance. The available literature on SP training mostly addresses instructor led training where the SPs are given direction on their roles. This study focuses on the use of peer and self evaluation as a tool to train SPs.</p> <p>Methods</p> <p>SPs at the medical school participated in a staff development and training programme which included a) self-assessment of their performance while observing video-tapes of their role play using a structured guide and b) peer group assessment of their performance under tutor guidance. The pre and post training performance in relation to authenticity of role play and quality of feedback was blindly assessed by students and tutors using a validated instrument and the scores were compared. A focus group discussion and a questionnaire assessed acceptability of the training programme by the SPs.</p> <p>Results</p> <p>The post-training performance assessment scores were significantly higher (p < 0.05) than the pre-training scores. The degree of improvement in the quality of feedback provided to students was more when compared to the improvement of role play. The acceptability of the training by the SPs was very satisfactory scoring an average of 7.6 out of 10. The majority of the SPs requested the new method of training to be included in their current training programme as a regular feature.</p> <p>Conclusion</p> <p>Use of structured self-reflective and peer-interactive, practice based methods of SP training is recommended to improve SP performance. More studies on these methods of training may further refine SP training and lead to improvement of SP performance which in turn may positively impact medical education.</p

Protein-coding and non-coding gene expression analysis in differentiating human keratinocytes using a three-dimensional epidermal equivalent

The epidermal compartment is complex and organized into several strata composed of keratinocytes (KCs), including basal, spinous, granular, and corniWed layers. The continuous process of self-renewal and barrier formation is dependent on a homeostatic balance achieved amongst KCs involving proliferation, diVerentiation, and cell death. To determine genes responsible for initiating and maintaining a corniWed epidermis, organotypic cultures comprised entirely of stratiWed KCs creating epidermal equivalents (EE) were raised from a submerged state to an air/liquid (A/L) interface. Compared to the array proWle of submerged cultures containing KCs predominantly in a proliferative (relatively undiVerentiated) state, EEs raised to an A/L interface displayed a remarkably consistent and distinct proWle of mRNAs. Cultures lifted to an A/L interface triggered the induction of gene groups that regulate proliferation, diVerentiation, and cell death. Next, diVerentially expressed microRNAs (miRNAs) and long noncoding (lncRNA) RNAs were identiWed in EEs. Several diVerentially expressed miRNAs were validated by qRT-PCR and Northern blots. miRNAs 203, 205 and Let-7b were up-regulated at early time points (6, 18 and 24 h) but downregulated by 120 h. To study the lncRNA regulation in EEs, we proWled lncRNA expression by microarray and validated the results by qRT-PCR. Although the diVerential expression of several lncRNAs is suggestive of a role in epidermal diVerentiation, their biological functions remain to be elucidated. The current studies lay the foundation for relevant model systems to address such fundamentally important biological aspects of epidermal structure and function in normal and diseased human skin

Fetal Window of Vulnerability to Airborne Polycyclic Aromatic Hydrocarbons on Proportional Intrauterine Growth Restriction

Background: Although the entire duration of fetal development is generally considered a highly susceptible period, it is of public health interest to determine a narrower window of heightened vulnerability to polycyclic aromatic hydrocarbons (PAHs) in humans. We posited that exposure to PAHs during the first trimester impairs fetal growth more severely than a similar level of exposure during the subsequent trimesters. Methods: In a group of healthy, non-smoking pregnant women with no known risks of adverse birth outcomes, personal exposure to eight airborne PAHs was monitored once during the second trimester for the entire cohort (n = 344), and once each trimester within a subset (n = 77). Both air monitoring and self-reported PAH exposure data were used in order to statistically estimate PAH exposure during the entire gestational period for each individual newborn. Results: One natural-log unit increase in prenatal exposure to the eight summed PAHs during the first trimester was associated with the largest decrement in the Fetal Growth Ratio (FGR) (23%, 95 % Confidence Interval (CI), 25 to20%), birthweight (2105 g, 95 % CI, 2188 to 222 g), and birth length (20.78 cm, 95 % CI, 21.30 to 20.26 cm), compared to the unit effects of PAHs during the subsequent trimesters, after accounting for confounders. Furthermore, a unit exposure during the first trimester was associated with the largest elevation in Cephalization Index (head to weight ratio) (3 mm/g, 95 % CI, 1 to 5 mm/g). PAH exposure was not associated with evidence of asymmetric growth restriction in this cohort

Presence of Helicobacter pylori in betel chewers and non betel chewers with and without oral cancers

<p>Abstract</p> <p>Background</p> <p>Betel chewing has been shown to predispose to periodontal disease and oral cancer. Studies show that people with gum disease are more likely to test positive for <it>Helicobacter pylori (H. pylori)</it>. It is not known if the lesions produced by betel quid and the resulting, chemical changes predispose to colonization by <it>H. pylori</it>. Further the role of this organism in oral cancer is not known. Our objective was to determine the presence of <it>H. pylori </it>in oral lesions of thirty oral cancer patients and to determine the presence of IgG antibodies to <it>H. pylori </it>in oral cancer patients who are betel chewers and non betel chewers, healthy betel chewers and healthy non-betel chewers and to compare the presence of <it>H</it>. <it>pylori </it>in these four groups. This case control study was conducted at the Cancer Institute Maharagama and the Department of Microbiology, Faculty of Medical Sciences, University of Sri Jayewardenepura.</p> <p>Methods</p> <p>One hundred and seventy three subjects, of whom fifty three were patients presenting with oral cancer to the Cancer Institute Maharagama, sixty healthy betel chewers and sixty healthy non-betel chewers from the Religious and Welfare Service Centre Maharagama were tested for <it>H. pylori </it>by serology. Thirty oral biopsies from oral cancer patients were cultured under microaerophilic condition to isolate <it>H. pylori</it>. The statistic used was Chi-square test.</p> <p>Results</p> <p>Of the fifty-three oral cancer patients, forty-four were betel chewers. Among the 53 oral cancer patients examined, ten of forty-four (10/44 = 22.7%) patients who are betel chewers and four of nine (4/9 = 44.4%) patients who are non-betel chewers were detected positive for IgG antibody against <it>H. pylori</it>. In the healthy group (betel chewers and non betel chewers) ten (16.7%) of the healthy betel chewers tested positive for <it>H. pylori </it>by serology. None of the healthy non-betel chewers tested positive for <it>H. pylori</it></p> <p>Fourteen [26.4%] of oral cancer patients tested positive for <it>H. pylori </it>by serology, of which two were also culture positive (Only thirty samples were cultured). The presence of <it>H. pylori </it>in betel chewers (with or without cancer) compared to non-betel chewers was statistically significant. (Chi-square test p < 0.05) The use of tobacco and areca nut in betel chewers was significant with the presence of <it>H. pylori </it>(p < 0.05).</p> <p>Conclusion</p> <p>There is a significant higher proportion of <it>H. pylori </it>in betel chewers compared to non-betel chewers but not between oral cancer patients compared to patients without oral cancer. Hence Betel chewing may predispose to colonisation with <it>H. pylori </it>in the digestive tract through swallowing the quid or during betel chewing.</p