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Waterborne gastrointestinal (GI) illnesses demonstrate seasonal increases associated with water quality and meteorological characteristics. However, few studies have been conducted on the association of hydrological parameters, such as streamflow, and seasonality of GI illnesses. Streamflow is correlated with biological contamination and can be used as proxy for drinking water contamination. We compare seasonal patterns of GI illnesses in the elderly (65 years and older) along the Ohio River for a 14-year period (1991–2004) to seasonal patterns of streamflow. Focusing on six counties in close proximity to the river, we compiled weekly time series of hospitalizations for GI illnesses and streamflow data. Seasonal patterns were explored using Poisson annual harmonic regression with and without adjustment for streamflow. GI illnesses demonstrated significant seasonal patterns with peak timing preceding peak timing of streamflow for all six counties. Seasonal patterns of illness remain consistent after adjusting for streamflow. This study found that the time of peak GI illness precedes the peak of streamflow, suggesting either an indirect relationship or a more direct path whereby pathogens enter water supplies prior to the peak in streamflow. Such findings call for interdisciplinary research to better understand associations among streamflow, pathogen loading, and rates of gastrointestinal illnesses.

The frequency of hospitalization among the elderly in the United States caused by gastrointestinal diseases between 1991 and 2004 increased dramatically, especially hospitalization of elderly individuals with nonspecific diagnoses. We analyzed 6 640 304 gastrointestinal disease–associated hospitalization records in this 14-year period by comparing the peak times of nonspecific gastrointestinal diseases with those of specific diseases. We found that most nonspecific gastrointestinal diseases peak concurrently with viral enteritis, suggesting a lack of diagnostic testing for viruses, which may adversely affect the efficiency of prevention, surveillance, and treatment efforts.

The aging of T cell memory is often considered in terms of senescence, a process viewed as decay and loss of memory T cells. How senescence would affect memory is a function of the initial structure of the memory repertoire and whether the clonotypes that make up the repertoire decay at random. We examine this issue using the T cell memory generated to the conserved influenza A epitope M158–66, which induces a strong, focused, but polyclonal CD8 T cell response in HLA-A2 individuals. We analyzed the CD8 T cell memory repertoires in eight healthy middle-aged and eight healthy older blood donors representing an average age difference of ∼27 y. Although the repertoires show broadly similar clonotype distributions, the number of observable clonotypes decreases significantly. This decrease disproportionally affects low-frequency clonotypes. Rank frequency analysis shows the same two-component clonotype distribution described earlier for these repertoires. The first component includes lower frequency clonotypes for which distribution can be described by a power law. The slope of this first component is significantly steeper in the older cohort. Generating a representative repertoire for each healthy cohort allowed agent-based modeling of the aging process. Interestingly, simple senescence of middle-aged repertoires is insufficient to describe the older clonotype distribution. Rather, a selective clonotype expansion must be included to achieve the best fit. We propose that responses to periodic virus exposure may drive such expansion, ensuring that the remaining clonotypes are optimized for continued protection.

Cross-reactivity of T cells is defined as recognition of two or more peptide–MHC complexes by the same T cell. Although examples of cross-reactivity have been reported, a detailed examination of cross-reactivity has not been performed. In this study, we took advantage of the high degree of polyclonality in the BV19 T cell repertoire responding to influenza M158–66 in HLA-A2 individuals to obtain a measure of simple cross-reactivity. We used substitutions that incrementally change the structure of the M158–66 peptide to measure how the HLA-A2–restricted response adapts to these changes. In three HLA-A2 adult subjects, we identified the BV19 clonotypes in the recall response to the influenza epitope M158–66 and 12 M1 peptides substituted at TCR contact position 63 or 65. The fraction of cross-reactive clonotypes in the M158–66 repertoire varied from 45–58% in the three donors. The extent of cross-reactivity, which is the additional number of peptides recognized by a single clonotype, is as high as six. We summarized the data using graph theory, with the cross-reactive clonotypes connecting the different HLA-A2 peptides recognized. The cross-reactive clonotypes form a well-connected network that could provide protection from virus-escape variants. We predict that any new pathogen with an epitope whose shape corresponds to that of the peptides that we studied would find a pre-existing repertoire ready to respond to it. We propose that in adult memory repertoires, previously encountered epitopes may have generated similar cross-reactive repertoires.

The surface-associated glycopeptides gp40, one of the most polymorphicCryptosporidiumantigens, and gp15, one of the most immunodominantCryptosporidiumantigens, are putative vaccine candidates because they mediate infectionin vitroand induce immune responsesin vivo. We evaluated antibody responses to these antigens before and after the first episode of symptomatic cryptosporidiosis in 51 children from a birth cohort study in an area in South India whereCryptosporidiumis endemic and a major cause of parasitic diarrhea. IgG levels to gp15 and to homotypic and heterotypic gp40 antigens were measured in pre- and postdiarrheal sera by enzyme-linked immunosorbent assay (ELISA). There was a significant IgG response to gp15 (P< 0.001) following the first episode of cryptosporidial diarrhea. Using a general additive model, we determined the estimated time of the peak IgG response to gp15 to be 9.3 weeks (confidence interval, 5.2 to 13.4) following the diarrheal episode. In a subset of 30 children infected withCryptosporidium hominissubtype Ia, there was a significant difference in IgG responses to homotypicC. hominisIa and to heterotypicCryptosporidium parvumII gp40 antigens (P= 0.035). However, there was also a significant correlation (P= 0.001) in the responses to both antigens in individual children, suggesting that while responses are in part subtype specific, there is significant cross-reactivity to both antigens. This is the first report of the characterization of immune responses to cryptosporidiosis in Indian children and the first study to investigate human immune responses to the polymorphic gp40 antigen. However, further studies are needed to determine whether immune responses to these antigens are protective against subsequent infections.

OBJECTIVES: To assess how influenza vaccination coverage in children is related to pneumonia and influenza (PI an exponential acceleration in the P&I rates with age was observed for each influenza season. State- and season-specific P&I rate accelerations were regressed against the percentage of vaccinated children, older adults, or both using mixed effects models. SETTING: U.S. population, 2002 to 2006. PARTICIPANTS: U.S. population aged 65 and older. MEASUREMENTS: State-level influenza annual vaccination coverage data in children and older adults were obtained from the National Immunization Survey and the Behavioral Risk Factor Surveillance System, respectively. RESULTS: Child influenza vaccination coverage was negatively associated with age acceleration in P&I, whereas influenza vaccination in the older adults themselves was not significantly associated with P&I in older adults. CONCLUSION: Vaccination of children against influenza may induce herd immunity against influenza for older adults and has the potential to be more beneficial to older adults than the existing policy of preventing influenza by vaccinating older adults themselves.

Visual analytics is the science of analytical reasoning that facilitates research through the use of interactive visual interfaces. New techniques of visual analytics are designed to aid the understanding of complex systems versus traditional blind-context rules to explore massive volumes of interrelated data. Nowhere else is visualization more important in analysis than in the emerging fields of life sciences, where amounts of collected data grow increasingly in exponential rates.The complexity of the immune system in immunology makes visual analytics especially important for understanding how this system works. In this context, our effort should be focused on avoiding accurate but potentially misleading use of visual interfaces. The proposed approach of data compression and visualization that reveal structural and functional features of immune responses enhances systemic and comprehensive description and provides the platform for hypothesis generation. Further, this approach can evolve into a powerful visual-analytical tool for prospective and real-time monitoring and can provide an intuitive and interpretable illustration of vital dynamics that govern immune responses in an individual and populations.The undertaken explorations demonstrate the critical role of novel techniques of visual analytics in stimulating research in immunology and other life sciences and in leading us to understanding of complex biological systems and processes.

This analysis examines the potential for the elderly to receive indirect protection from pneumonia and influenza (P&I) from vaccination of children. Using data from the Centers for Medicare and Medicaid Services, the National Immunization Survey, and the Behavioral Risk Factor Surveillance System, mixed-effects models were used to assess associations between vaccination coverage and P&I on the state level overall and by urbanicity and income. As vaccination coverage in children increased, the state-level P&I rates in seniors decreased (beta=-0.040, -0.074 to 0.006), where beta represents the expected change in the logged age-associated rate of disease increase for a one-percentage point increase in vaccination coverage. Increasing vaccination coverage in the elderly was associated with an increase in P&I rates (beta=0.045, 0.011-0.077) in seniors. The degree of association was more prominent in urban and high income areas. The consistent associations between influenza in the elderly and vaccination coverage in children suggest that routine vaccination of children may impart some indirect protection to the elderly.

Please cite this paper as: Lofgren et al. (2010) Disproportional effects in populations of concern for pandemic influenza: insights from seasonal epidemics in Wisconsin, 1967–2004. Influenza and Other Respiratory Viruses 4(4), 205–212. Background Influenza infections pose a serious burden of illness in the United States. We explored age, influenza strains, and seasonal epidemic curves in relation to influenza-associated mortality. Methods The state of Wisconsin death records for the years 1967–2004 were analyzed for three distinct populations: children, general population, and elderly. Yearly parameters of duration, intensity, and peak timing were obtained from Annual Harmonic Regression coefficients. Results Overall, elderly had the highest rate and intensity of influenza mortality. The children and infant subpopulations showed an earlier and wider range in duration of peak timing than elderly. During A/Hong Kong/1/68 pandemic years, the elderly subpopulation showed no change in mortality rates while a sharp increase was observed for the children and infant subpopulations. In epidemic years such as 1966–1969, children and infants showed a dramatic decrease in the severity of influenza outbreaks over time. The elderly had increased baseline mortality in years (1986–1987) where predominant strain was characterized as A/Singapore/6/86. Conclusions Our findings indicate that the younger populations may have benefited from the lack of a major shift in viral strains for a number of decades. Furthermore, we demonstrate considerable heterogeneity in the spread of seasonal influenza across age categories, with implications both for the modeling of influenza seasonality, risk assessment, and effective distribution and timing of vaccine and prophylactic interventions.

Background Pneumonia and influenza (P&I) is a major cause of morbidity and mortality in the USA, particularly in elderly people. Recent research indicates that P&I may be linked to socioeconomic conditions associated with interactions of children with vulnerable elderly people that may proliferate the spread of disease. This study assessed the associations between four sociodemographic characteristics—median county income, Gini index, youth dependency ratio and proportion of co-residential caregiver grandparents—and P&I on the county level overall and by age group. Methods All hospitalisations due to P&I from 1991 to 2004 were abstracted from the Centers for Medicare and Medicaid Services database and categorised by influenza year (July–June) and age category. Using generalised estimating equations, associations between P&I rates and four sociodemographic variables were assessed and models were stratified by income to assess income as a potential effect modifier. Results P&I rates were higher in counties with lower median income. In low-income counties, high levels of live-in grandparental caregivers were associated with consistently higher levels of pneumonia and influenza rates. The Gini index was positively associated with disease rates, particularly in younger age groups. Discussion These results suggest complex relationships between sociodemographic characteristics and P&I outcomes for elderly people, particularly those related to children. The strength of the relationship between the proportion of grandparental caregivers and disease rates decreases with age, which may caregiving patterns, or may serve as a proxy for related sociodemographic characteristics. These findings merit further research to understand better how area-level factors affect P&I patterns in elderly people.

OBJECTIVES: To compare the demographic and geographic patterns of pneumonia and influenza (P&I) hospitalizations in older adults with dementia with those of the U.S. population and to examine the relationship between healthcare accessibility and P&I. DESIGN: Observational study using historical medical claims from the Centers for Medicare and Medicaid Services (CMS) and CMS records supplemented with information derived from other large national sources. SETTING: Retrospective analysis of medical records uniformly collected over a 5-year period with comprehensive national coverage. PARTICIPANTS: A study population representative of more than 95% of all people aged 65 and older residing in the continental United States. MEASUREMENTS: Six million two hundred seventy-seven thousand six hundred eighty-four records of P&I between 1998 and 2002 were abstracted, and county-specific outcomes for hospitalization rates of P&I, mean length of hospital stay, and percentage of deaths occurring in a hospital setting were estimated. Associations with county-specific elderly population density, percentage of nursing home residents, median household income per capita, and rurality index were assessed. RESULTS: Rural and poor counties had the highest rate of P&I and percentage of influenza. Patients with dementia had a lower frequency of influenza diagnosis, a shorter length of hospital stay, and 1.5 times as high a rate of death as the national average. CONCLUSION: The results suggest strong disparities in healthcare practices in rural locations and vulnerable populations; infrastructure, proximity, and access to healthcare are significant predictors of influenza morbidity and mortality. These findings have important implications for influenza vaccination, testing, and treatment policies and practices targeting the growing fraction of patients with cognitive impairment.

The time-dependent changes of human memory T cell repertoires are still poorly understood. We define a T cell memory repertoire as the pool of clonotypic lineages participating in a recall response to the influenza M158–66 epitope. In HLA-A2 individuals, this response predominantly uses BV19 chains with Arg-Ser (RS) in the CDR3 loop. We previously showed that the repertoire is polyclonal with a large fraction of clonotype that are only observed once. In this study, we perform longitudinal analyses of memory repertoires in three middle-aged individuals at times that spanned from 7 to 10 years. In these individuals, who are well into thymic involution, a substantial number of clonotypes were stable, e.g., detected at two times. The shape of the repertoire was stable over time as reflected by a number of repertoire characteristics, including singletons, i.e., the fraction of clonotypes observed only once, and repertoire diversity. However, the RS-clonotype subset showed a significant decline in the fraction of singletons and in clonotypic diversity. Thus, repertoire structure is maintained over time by a recruitment of non-RS-clonotypes and a shift of existing RS-clonotypes into higher frequencies. The recruitment of new clonotypes into the low-frequency component of the repertoire implies a role for these clonotypes.

Extreme weather affects the timing and intensity of infectious outbreaks, the resurgence and redistribution of infections, and it causes disturbances in human-environment interactions. Environmental stressors with high thermoregulatory demands require susceptible populations to undergo physiological adaptive processes potentially compromising immune function and increasing susceptibility to infection. In assessing associations between environmental exposures and infectious diseases, failure to account for a latent period between time of exposure and time of disease manifestation may lead to severe underestimation of the effects. In a population, health effects of an episode of exposure are distributed over a range of time lags. To consider such time-distributed lags is a challenging task given that the length of a latent period varies from hours to months and depends on the type of pathogen, individual susceptibility to the pathogen, dose of exposure, route of transmission, and many other factors. The two main objectives of this communication are to introduce an approach to modeling time-distributed effect of exposures to infection cases and to demonstrate this approach in an analysis of the association between high ambient temperature and daily incidence of enterically transmitted infections. The study is supplemented with extensive simulations to examine model sensitivity to response magnitude, exposure frequency, and extent of latent period.

We developed methodology for and conducted a meta-analysis to examine how seasonal patterns of cryptosporidiosis, a primarily waterborne diarrheal illness, relate to precipitation and temperature fluctuations worldwide.Monthly cryptosporidiosis data were abstracted from 61 published epidemiological studies that cover various climate regions based on the Köppen Climate Classification. Outcome data were supplemented with monthly aggregated ambient temperature and precipitation for each study location. We applied a linear mixed-effect model to relate the monthly normalized cryptosporidiosis incidence with normalized location-specific temperature and precipitation data. We also conducted a sub-analysis of associations between the Normalized Difference Vegetation Index (NDVI), a remote sensing measure for the combined effect of temperature and precipitation on vegetation, and cryptosporidiosis in Sub-Saharan Africa.Overall, and after adjusting for distance from the equator, increases in temperature and precipitation predict an increase in cryptosporidiosis; the strengths of relationship vary by climate subcategory. In moist tropical locations, precipitation is a strong seasonal driver for cryptosporidiosis whereas temperature is in mid-latitude and temperate climates. When assessing lagged relationships, temperature and precipitation remain strong predictors. In Sub-Saharan Africa, after adjusting for distance from the equator, low NDVI values are predictive of an increase in cryptosporidiosis in the following month.In this study we propose novel methodology to assess relationships between disease outcomes and meteorological data on a global scale. Our findings demonstrate that while climatic conditions typically define a pathogen habitat area, meteorological factors affect timing and intensity of seasonal outbreaks. Therefore, meteorological forecasts can be utilized to develop focused prevention programs for waterborne cryptosporidiosis.

We show that the microsporidian fungus Enterocytozoon bieneusi is associated with lower rates of weight gain in children in Uganda with persistent diarrhea. This relationship remained after controlling for HIV and concurrent cryptosporidiosis. Children with microsporidiosis were predicted to weigh 1.3 kg less than children without microsporidiosis at 5 years of age.

This communication provides an illustration for the use of computer simulations in human immunology. When traditional experiments are impossible, unethical, or unfeasible, in silico modeling procedures may help to fill the gaps in our knowledge of an immune system response to a pathogen. In our study, we define terms and properties of modeled entities: "a clonotype", its distribution, and rank-frequency summaries, and describe properties associated with each of these three clonotype-related entities. We simulate a multistage dynamic process of an immune memory response to influenza. We believe that illustrated properties of fractality and self-similarity might arise due to the following process. The memory T cells operate in a complex environment of shifting pathogen concentrations, increasing and then decreasing inflammatory signals, and multiple interactions with other immune cells and their infected targets. Therefore, a fractal structure to such a population would represent an optimization in terms of percolation into immune/inflammatory space.

Studies of DNA tumor viruses have provided important insights into fundamental cellular processes and oncogenic transformation. They have revealed, for example, that upon expression of virally encoded proteins, cellular pathways involved in DNA repair and cell cycle control are disrupted. Herein, evidence is presented that BRCT-related regions are present in the helicase domains of the viral initiators encoded by the Polyomaviridae and Papillomaviridae viral families. Of interest, BRCT domains in cellular proteins recruit factors involved in diverse pathways, including DNA repair and the regulation of cell cycle progression. Therefore, the viral BRCT-related regions may compete with host BRCT domains for particular cellular ligands, a process that would help to explain the pleiotropic effects associated with infections with many DNA tumor viruses.

Stunting or reduced linear growth is very prevalent in low-income countries. Recent studies have demonstrated a causal relationship between alterations in the gut microbiome and moderate or severe acute malnutrition in children in these countries. However, there have been no primary longitudinal studies comparing the intestinal microbiota of persistently stunted children to that of non-stunted children in the same community. In this pilot study, we characterized gut microbial community composition and diversity of the fecal microbiota of 10 children with low birth weight and persistent stunting (cases) and 10 children with normal birth weight and no stunting (controls) from a birth cohort every 3 months up to 2 years of age in a slum community in south India. There was an increase in diversity indices (P

To assess whether adolescent obesity is associated with risk for development of major depressive disorder (MDD) or anxiety disorder. Obesity has been linked to psychosocial difficulties among youth.Analysis of a prospective community-based cohort originally from upstate New York, assessed four times over 20 years. Participants (n = 776) were 9 to 18 years old in 1983; subsequent assessments took place in 1985 to 1986 (n = 775), 1991 to 1994 (n = 776), and 2001 to 2003 (n = 661). Using Cox proportional hazards analysis, we evaluated the association of adolescent (age range, 12-17.99 years) weight status with risk for subsequent MDD or anxiety disorder (assessed at each wave by structured diagnostic interviews) in males and females. A total of 701 participants were not missing data on adolescent weight status and hador = 1 subsequent assessments. MDD and anxiety disorder analyses included 674 and 559 participants (free of current or previous MDD or anxiety disorder), respectively. Adolescent obesity was defined as body mass index above the age- and gender-specific 95th percentile of the Centers for Disease Control and Prevention growth reference.Adolescent obesity in females predicted an increased risk for subsequent MDD (adjusted hazard ratio (HR) = 3.9; 95% confidence interval (CI) = 1.3, 11.8) and for anxiety disorder (HR = 3.8; CI = 1.3, 11.3). Adolescent obesity in males was not statistically significantly associated with risk for MDD (HR = 1.5; CI = 0.5, 3.5) or anxiety disorder (HR = 0.7; CI = 0.2, 2.9).Females obese as adolescents may be at increased risk for development of depression or anxiety disorders.

We propose an extension of the Harezlak and Heckman (J. Comput. Graph. Statist. 2001; 10(4): 713-729) test for detecting local extrema to the longitudinal data setting. We use penalized spline regression techniques (Statist. Sci. 1996; 11:89-102) to provide a computationally efficient method of testing for relatively large data sets. We estimate the p-values of our test, LongCriSP, with a smoothed bootstrap. Our simulation studies indicate that the test is generally conservative and has power exceeding 70 per cent at the alpha = 0.1 nominal level in most considered settings. Finally, we apply our testing procedure to the longitudinal measurements of body mass index of former prisoners of war in Vietnam and conclude that the mean population curve exhibits non-monotone behaviour.

Continuous access to adequate quantities of safe water is essential for human health and socioeconomic development. Piped water systems (PWSs) are an increasingly common type of water supply in rural African small towns. Despite providing the highest and most flexible level of service with better microbiological water quality to their users, these systems remain vulnerable to rural water sustainability challenges. We assessed temporal and spatial patterns in water consumption from public standpipes of four PWSs in Ghana in order to assess clean water demand relative to other available water sources. Low water consumption was evident in all study towns, which manifested temporally and spatially. Temporal variability in water consumption that is negatively correlated with rainfall is an indicator of rainwater preference when it is available. Furthermore, our findings show that standpipes in close proximity to alternative water sources such as streams and hand-dug wells suffer further reductions in water consumption. Qualitative data suggest that consumer demand in the study towns appears to be driven more by water quantity, accessibility, and perceived aesthetic water quality, as compared to microbiological water quality or price. In settings with chronic under-utilization of improved water sources, increasing water demand through household connections, improving water quality with respect to taste and appropriateness for laundry, and educating residents about health benefits of using piped water should be prioritized. Continued consumer demand and sufficient revenue generation are important attributes of a water service that ensure its function over time. Our findings suggest that analyzing water consumption of existing metered PWSs in combination with qualitative approaches may enable more efficient planning of community-based water supplies and support sustainable development.

Diarrhea causes significant morbidity and mortality in Indian children under 5 years of age. Flies carry enteric pathogens and may mediate foodborne infections. In this study, we characterized fly densities as a determinant of infectious diarrhea in a longitudinal cohort of 160 urban and 80 rural households with 1,274 individuals (27% under 5 years of age) in Vellore, India. Household questionnaires on living conditions were completed at enrollment. Fly abundance was measured during the wet and dry seasons using fly ribbons placed in kitchens. PCRs for enteric bacteria, viruses, and protozoa were performed on 60 fly samples. Forty-three (72%) fly samples were positive for the following pathogens: norovirus (50%), Salmonella spp. (46.7%), rotavirus (6.7%), and Escherichia coli (6.7%). Ninety-one episodes of diarrhea occurred (89% in children under 5 years of age). Stool pathogens isolated in 24 of 77 (31%) samples included E. coli , Shigella spp., Vibrio spp., Giardia , Cryptosporidium , and rotavirus. Multivariate log-linear models were used to explore the relationships between diarrhea and fly densities, controlling for demographics, hygiene, and human-animal interactions. Fly abundance was 6 times higher in rural than urban sites ( P < 0.0001). Disposal of garbage close to homes and rural living were significant risk factors for high fly densities. The presence of latrines was protective against high fly densities and diarrhea. The adjusted relative risks of diarrheal episodes and duration of diarrhea, associated with fly density at the 75th percentile, were 1.18 (95% confidence interval [CI], 1.03 to 1.34) and 1.15 (95% CI, 1.02 to 1.29), respectively. Flies harbored enteric pathogens, including norovirus, a poorly documented pathogen on flies.

Summary Background Childhood vaccination remains the focus of heated public debate. Parents struggle to understand the potential risks associated with vaccination but both parents and physicians assume that they understand the risks associated with infection. This study was done to characterise how modern vaccination practices have altered patient risks from infection. Methods In this modelling study, we use mathematical analysis to explore how modern-era vaccination practices have changed the risks of severe outcomes for some infections by changing the landscape for disease transmission. We show these effects using published data from outbreaks in the USA for measles, chickenpox, and rubella. Calculation of risk estimation was the main outcome of this study. Findings Our calculations show that negative outcomes are 4·5 times worse for measles, 2·2 times worse for chickenpox, and 5·8 times worse for rubella than would be expected in a pre-vaccine era in which the average age at infection would have been lower. Interpretation As vaccination makes preventable illness rarer, for some diseases, it also increases the expected severity of each case. Because estimates of case risks rely on data for severity generated during a pre-vaccine era they underestimate negative outcomes in the modern post-vaccine epidemiological landscape. Physicians and parents should understand when making decisions about their children's health and safety that remaining unvaccinated in a predominantly vaccine-protected community exposes their children to the most severe possible outcomes for many preventable diseases. Funding None.

Climate change and increasing urbanization have intensified scientific interest in understanding the impact of vegetation cover on human health. While the elderly population (persons 65+y.o.) continues to grow, environmental determinants for asthma in this group remain poorly understood. Using spatial and time series analysis we investigated the effect of vegetation cover as measured by the Normalized Difference Vegetation Index (NDVI) on asthma hospitalization rates (AHR)(ICD-9 codes 493.0-9) among Medicare recipients in seven northeastern United States. We considered potential confounders, including income, land cover category, seasonal influenza activity, and population density, classified as urban, suburban, and rural. Time-series analysis identified seasonal patterns in elderly asthma hospitalizations as counter-phase with NDVI: when vegetation vigor increases, AHR decreases (R 2 =0.59, p=0.001). Winter peaks of influenza correlated with an increase in AHR (R 2 =0.43, p=0.001). Spatial multivariate analysis found HRs increased significantly (RR=1.048, 95% CI:1.072-1.086, p=0.001) as population density increased. Regardless of location, living in poverty increased AHR (RR=1.014, 95% CI:1.026-1.018, p=0.001). After adjusting for income and percent elderly population, evergreen vegetation in urban areas demonstrated a small, yet protective effect (RR=0.998, 95% CI:0.993-0.997, p=0.02). These results suggest that urban evergreen vegetation cover could be an important factor for reducing the risk of elderly asthma hospitalizations.

SUMMARYDiarrhoeal diseases are major causes of morbidity and mortality in developing countries. This longitudinal study aimed to identify controllable environmental drivers of intestinal infections amidst a highly contaminated drinking water supply in urban slums and villages of Vellore, Tamil Nadu in southern India. Three hundred households with children (P

Arguably one of the most important effects of climate change is the potential impact on human health. While this is likely to take many forms, the implications for future transmission of vector-borne diseases (VBDs), given their ongoing contribution to global disease burden, are both extremely important and highly uncertain. In part, this is owing not only to data limitations and methodological challenges when integrating climate-driven VBD models and climate change projections, but also, perhaps most crucially, to the multitude of epidemiological, ecological and socio-economic factors that drive VBD transmission, and this complexity has generated considerable debate over the past 10–15 years. In this review, we seek to elucidate current knowledge around this topic, identify key themes and uncertainties, evaluate ongoing challenges and open research questions and, crucially, offer some solutions for the field. Although many of these challenges are ubiquitous across multiple VBDs, more specific issues also arise in different vector–pathogen systems.

The session will explore past collaborations between the statistician panelists and public health departments to highlight approaches that have and have not been effective and to recommend effective, sustainable relationship strategies for mutual advancement of practical disease surveillance and relevant academic research. Panelists will describe experiences working with health departments, including actual applications as examples. Issues discussed will include requirements analysis, scoping technical problems for health department utility, adaptation of traditional statistical methods, and management of changing data environments. Panelists will derive advice for public health practitioners seeking help in forming relationships, framing problems, communicating results, and seeking funding.

Influenza (or “flu”) leads to the hospitalization of more than 200,000 people yearly and results in 36,000 deaths from flu or flu-related complications in the United States ([15][1]), striking both the elderly and infant populations particularly hard ([24][2]). Two members of the

We use mathematically rigorous definitions of epidemiological concepts in order to derive a sequential combinatorial model of disease outbreak decomposition. We define the idea of a population specific ‘disease signature’ and use this in order to decompose and further understand outbreaks as incidents of spatial and temporal spread of disease exposure both in, and across, populations. This allows us to differentiate between different disease spread scenarios with a level of sensitivity that previous models were unable to provide. This perspective leads us to propose a new practical definition for ‘outbreak’. In addition, we are able to use this model to understand, estimate, and, in some cases, correct for, the likely instances of reporting error inherent in disease surveillance. We demonstrate our model first with a hypothetical outbreak scenario and then in an analysis of suspected outbreaks of waterborne diseases in Massachusetts (MA) in 1995.

We propose an analytical and conceptual framework for a systematic and comprehensive assessment of disease seasonality to detect changes and to quantify and compare temporal patterns. To demonstrate the proposed technique, we examined seasonal patterns of six enterically transmitted reportable diseases (EDs) in Massachusetts collected over a 10-year period (1992–2001). We quantified the timing and intensity of seasonal peaks of ED incidence and examined the synchronization in timing of these peaks with respect to ambient temperature. All EDs, except hepatitis A, exhibited well-defined seasonal patterns which clustered into two groups. The peak in daily incidence of Campylobacter and Salmonella closely followed the peak in ambient temperature with the lag of 2–14 days. Cryptosporidium, Shigella, and Giardia exhibited significant delays relative to the peak in temperature (~40 days, P

Seasonality, a systematic periodic occurrence of events over the course of a year, is a well-known phenomenon in life and health sciences. Understanding seasonal fluctuations in diseases patterns presents us with a major challenge. To develop efficient strategies for disease prevention and control, we need to grasp the main determinants of temporal variations and their interactions. This paper will introduce the notion of seasonality by outlining several of its factors, using as illustrations respiratory and enteric water- or food-borne infections.

The recent adoption of electronic technologies for use in management of personal health data have been accompanied by a commensurate level of concern about privacy. Public health authorities have been able to continue their full access to personal information, while restricting the information given to academic health researchers through the practice of aggregation. Through this band-aid strategy, there is a very real potential that critical pieces of information are missing for the purposes of research. While this might be a logical sacrifice in order to preserve individual privacy, quantitative analysis of the privacy gained through this method of aggregation shows that little, if any, benefit is achieved. If aggregation were the sole available means to reach the aims of both privacy and research, then further analysis of the practice of aggregation would be unnecessary. Yet suitable privacy protection techniques abound, enabling academic research to progress while adding true protection to individual health information.

Outdoor carbon monoxide comes mainly from vehicular emissions, and high concentrations occur in areas with heavy traffic congestion. CO binds to hemoglobin, forming carboxyhemoglobin (COHb), and reduces oxygen delivery. We investigated the link between the adverse effects of CO on the respiratory system using COHb as a marker for chronic CO exposure. We examined the relationship between acute respiratory infections (ARIs) and COHb concentrations in school-age children living in urban and suburban areas of Quito, Ecuador. We selected three schools located in areas with different traffic intensities and enrolled 960 children. To adjust for potential confounders we conducted a detailed survey. In a random subsample of 295 children, we determined that average COHb concentrations were significantly higher in children attending schools in areas with high and moderate traffic, compared with the low-traffic area. The percentage of children with COHb concentrations above the safe level of 2.5% were 1, 43, and 92% in low-, moderate-, and high-traffic areas, respectively. Children with COHb above the safe level are 3.25 [95% confidence interval (CI), 1.65–6.38] times more likely to have ARI than children with COHb < 2.5%. Furthermore, with each percent increase in COHb above the safety level, children are 1.15 (95% CI, 1.03–1.28) times more likely to have an additional case of ARI. Our findings provide strong evidence of the relation between CO exposure and susceptibility to respiratory infections.

Russia has the world's second highest incarceration rate after the USA. These two countries have less than 7% of the world population, but they harbor approximately one-third of all prisoners (i). Although the issues of morbidity and mortality in its penitentiaries are of great consequence, there is little literature on prison health in Russia. The review of mortality and morbidity in Russian penitentiaries by Bobrik et al. fills this gap and produces a surprising conclusion: prisoners in Russia (who are mostly males) have a substantially lower risk of death than free-living Russian males.

Daily disease monitoring via a public health surveillance system provides valuable information on population risks. Efficient statistical tools for early detection of rapid changes in the disease incidence are a must for modern surveillance. The need for statistical tools for early detection of outbreaks that are not based on historical information is apparent. A system is discussed for monitoring cases of infections with a view to early detection of outbreaks and to forecasting the extent of detected outbreaks. We propose a set of adaptive algorithms for early outbreak detection that does not rely on extensive historical recording. We also include knowledge of infection disease epidemiology into forecasts. To demonstrate this system we use data from the largest water-borne outbreak of cryptosporidiosis, which occurred in Milwaukee in 1993. Historical data are smoothed using a loess-type smoother. Upon receipt of a new datum, the smoothing is updated and estimates are made of the first two derivatives of the smooth curve, and these are used for near-term forecasting. Recent data and the near-term forecasts are used to compute a color-coded warning index, which quantify the level of concern. The algorithms for computing the warning index have been designed to balance Type I errors (false prediction of an epidemic) and Type II errors (failure to correctly predict an epidemic). If the warning index signals a sufficiently high probability of an epidemic, then a forecast of the possible size of the outbreak is made. This longer term forecast is made by fitting a ‘signature’ curve to the available data. The effectiveness of the forecast depends upon the extent to which the signature curve captures the shape of outbreaks of the infection under consideration.

Individuals of lower socioeconomic position smoke at higher rates than those of higher socioeconomic position. Because of this disparity, the National Cancer Institute has called for studies of targeted tobacco marketing to clarify mechanisms contributing to higher tobacco use among low-income Americans and other high-risk populations.We observed tobacco industry marketing in six Boston area communities (two of high socioeconomic position and four of low position; total of 41 observations) and in selected print publications that circulated in those communities during a 22-month period in 2000-2002.On average, there were fewer tobacco advertisements in the higher socioeconomic communities, compared to the lower socioeconomic communities (P0.001). In the low socioeconomic communities, there were more than three times as many brand advertisements as youth access signs (P = 0.0012). Although brand advertisements outnumbered smoke-free signs, on average, there was no difference in the ratio of brand advertisements to smoke-free signs in low and high socioeconomic communities (P = 0.06).The tobacco industry is actively present in community settings, particularly in communities with a low socioeconomic profile (SEP). Tobacco control researchers and advocates need to continue to monitor the tobacco industry's behavior at the community level and develop strategies to counter this behavior.

Objective: The longitudinal relationship between the consumption of energy-dense snack (EDS) foods and relative weight change during adolescence is uncertain. Using data from the Massachusetts Institute of Technology Growth and Development Study, the current analysis was undertaken to examine the longitudinal relationship of EDS food intake with relative weight status and percentage body fat and to examine how EDS food consumption is related to television viewing. Research Methods and Procedures: One hundred ninety-six nonobese premenarcheal girls 8 to 12 years old were enrolled between 1990 and 1993 and followed until 4 years after menarche. At each annual follow-up visit, data were collected on percentage body fat (%BF), BMI z score, and dietary intake. Categories of EDS foods considered were baked goods, ice cream, chips, sugar-sweetened soda, and candy. Results: At study entry, girls had a mean ± SD BMI z score of −0.27 ± 0.89, consumed 2.3 ± 1.7 servings of EDS foods per day, and consumed 15.7 ± 8.1% of daily calories from EDS foods. Linear mixed effects modeling indicated no relationship between BMI z score or %BF and total EDS food consumption. Soda was the only EDS food that was significantly related to BMI z score over the 10-year study period, but it was not related to %BF. In addition, a significant, positive relationship was observed between EDS food consumption and television viewing. Discussion: In this cohort of initially nonobese girls, overall EDS food consumption does not seem to influence weight status or fatness change over the adolescent period.

Purpose Assess the relative frequency of Cryptosporidium infections and risk factors for infection in Cherepovets, Russia. Methods In June 1999, data on demographic, socioeconomic, hygienic characteristics, and recent gastrointestinal illness were collected on 50 community-recruited adults and 50 blood donors. The community group then maintained daily diaries of exposures and gastrointestinal symptoms for 5 months. Sera samples at the inception and conclusion of the study were tested for antibody responses to the 15/17 kDa and 27 kDa Cryptosporidium antigens using mini-immunoblots. Results At the inception, 68% and 88% of study participants had detectable serological responses to 15/17 kDa and 27 kDa antigens. Older age was associated with stronger antibody responses to both antigens. Attendance at swimming pools was associated with stronger responses to both antigens in predominantly male blood donors. Over the follow-up period, drinking non-boiled water from shallow draw-wells was associated with an increase in serological response to the 27 kDa antigen. Self-reported gastrointestinal illness was not associated with an increase in serological response. Conclusions The prevalence of positive serological responses in Cherepovets was higher than in most prior Cryptosporidium serosurveys in non-outbreak communities. Drinking water is an important pathway for infection.

Dairy food consumption and body weight and fatness studied longitudinally over the adolescent period

Background: This report describes the prevalence of overweight and obesity and estimates the disease burden associated with excess weight in ambulatory Veterans Affairs (VA) patients. Methods: Height and weight were measured, and self-reported age and self-reported morbidities were obtained for 1,731 patients. Prevalence odds ratios explain the association of self-reported disease on increasing weight status category using body mass index. Results: Seventy-five percent of the participants were overweight or obese. Obesity was significantly higher in the younger patients. Graded increases in odds ratios were observed with increasing severity of overweight and obesity for all morbidities, except heart disease. Conclusion: Overweight, obesity, and associated disease burden are prevalent in the VA health care system, particularly in younger VA patients, which may contribute to the higher prevalence of certain morbidities observed in VA populations compared with private sector outpatients. Department of Veterans Affairs should emphasize obesity prevention and treatment during the design and implementation of ambulatory care services.

The risk factors for acquisition of cryptosporidial infection in resource-poor settings are poorly understood. A nested case-control study was conducted to assess factors associated with childhood cryptosporidiosis (detected by stool polymerase chain reaction) in an endemic, Indian slum community using data from two community-based studies with 580 children followed prospectively until their second birthday. Factors were assessed for overall cryptosporidiosis (N = 406), and for multiple (N = 208), asymptomatic (N = 243), and symptomatic (N = 163) infections, respectively. Presence of older siblings (odds ratio [OR] = 1.88, P = 0.002) and stunting at 6 months of age (OR = 1.74, P = 0.019) were important risk factors for childhood cryptosporidiosis. Always boiling drinking water before consumption, the use of a toilet by all members of the family, and maternal age ≥ 23 years were protective. These results provide insights into acquisition of childhood cryptosporidiosis in settings with poor environmental sanitation, contaminated public water supply systems, and close human-animal contact. Disease control strategies will require a multifaceted approach.

Objective To estimate the burden and assess prenatal and postnatal determinants of illnesses experienced by children residing in a semiurban slum, during the first 1000 days of life. Design Community-based birth cohort Setting Southern India Participants Four hundred and ninety-seven children of 561 pregnant women recruited and followed for 2 years with surveillance and anthropometry. Main outcome measure Incidence rates of illness; rates of clinic visits and hospitalisations; factors associated with low birth weight, various illnesses and growth. Results Data on 10 377.7 child-months of follow-up estimated an average rate of 14.8 illnesses/child-year. Gastrointestinal and respiratory illnesses were 20.6% and 47.8% of the total disease burden, respectively. The hospitalisation rate reduced from 46/100 child-years during infancy to 19/100 child-years in the second year. Anaemia during pregnancy (OR=2.3, 95% CI=1.08 to 5.18), less than four antenatal visits (OR=6.8, 95% CI=2.1 to 22.5) and preterm birth (OR=3.3, 95% CI=1.1 to 9.7) were independent prenatal risk factors for low birth weight. Female gender (HR=0.88, 95% CI=0.79 to 0.99) and 6 months of exclusive breast feeding (HR=0.76, 95% CI=0.66 to 0.88) offered protection against all morbidity. Average monthly height and weight gain were lower in female child and children exclusively breast fed for 6 months. Conclusions The high morbidity in Indian slum children in the first 1000 days of life was mainly due to prenatal factors and gastrointestinal and respiratory illness. Policymakers need disease prevalence and pathways to target high-risk groups with appropriate interventions in the community.

Background Parkinson’s disease affects facial, vocal and trunk muscles. As symptoms progress, facial expression becomes masked, limiting the person’s ability to communicate emotions and intentions to others. As people with the disease live and reside in their homes longer, the burden of caregiving is unmitigated by social and emotional rewards provided by an expressive individual. Little is known about how adults living with Parkinson’s disease manage their social lives and how an inability to be emotionally expressive can affect social connections and health. Because social networks have been shown to be crucial to the overall well-being of people living with chronic diseases, research is needed on how expressive capacity affects life trajectories and health. Methods/Design The overall objective is to understand the emergence and evolution of the trajectories of the self-management of the social lives of people living with Parkinson’s disease. The central hypothesis is that expressive capacity predicts systematic change in the pattern of social self-management and quality of life outcomes. The specific aims of this 3-year longitudinal study of 120 people with the disease and a maximum of 120 care partners are: 1) characterize social self-management trajectories over a 3-year period; 2) estimate the degree to which expressive nonverbal capacity predicts the trajectory; and 3) determine the moderating effect of gender on the association between expressive capacity and change in social self-management. Each participant will be assessed 14 times to detect rapid and non-linear changes in social participation and management of social activities; social network; and social comfort, general health and well-being. Discussion This project will provide evidence to guide the development of interventions for supporting social integration of those living with Parkinson’s disease, thus leading to improved overall health. It focuses on the novel construct of social self-management and known factors—expressive capacity and gender—that contribute to stigmatization. The repeated measures design detects triggers of rapid changes in social and health outcomes.

Introduction Antibiotic pressure contributes to rising antibiotic resistance. Policy guidelines encourage rational prescribing behavior, but effectiveness in containing antibiotic use needs further assessment. This study therefore assessed the patterns of antibiotic use over a decade and analyzed the impact of different modes of guideline development and dissemination on inpatient antibiotic use. Methods Antibiotic use was calculated monthly as defined daily doses (DDD) per 100 bed days for nine antibiotic groups and overall. This time series compared trends in antibiotic use in five adjacent time periods identified as ‘Segments,’ divided based on differing modes of guideline development and implementation: Segment 1– Baseline prior to antibiotic guidelines development; Segment 2– During preparation of guidelines and booklet dissemination; Segment 3– Dormant period with no guidelines dissemination; Segment 4– Booklet dissemination of revised guidelines; Segment 5– Booklet dissemination of revised guidelines with intranet access. Regression analysis adapted for segmented time series and adjusted for seasonality assessed changes in antibiotic use trend. Results Overall antibiotic use increased at a monthly rate of 0.95 (SE = 0.18), 0.21 (SE = 0.08) and 0.31 (SE = 0.06) for Segments 1, 2 and 3, stabilized in Segment 4 (0.05; SE = 0.10) and declined in Segment 5 (−0.37; SE = 0.11). Segments 1, 2 and 4 exhibited seasonal fluctuations. Pairwise segmented regression adjusted for seasonality revealed a significant drop in monthly antibiotic use of 0.401 (SE = 0.089; p

Using a specifically designed diagnostic PCR assay with nested primers the following could be achieved: (1) a group of 22 clinically indistinguishable women attending an infertility clinic, 18 with repeated embryo transfer failure, and asymptomatic for HSV-1 could be divided into two subgroups after testing their menstrual blood. An HSV-DNA positive (50%) and HSV-DNA negative group (50%) could be distinguished. None of the four controls were positive; (2) semen from 154 infertile and 24 fertile men was tested in relation to infertility. In the group of infertile men 37 (24%) were HSV-DNA positive but none of the fertile control (0%) was positive; (3) treatment of both partners with an antiviral drug resulted in two pregnancies; (4) HLA data on four of the couples in which the wife's menstrual blood was HSV positive was compared to seven HSV negative couples and 22 infertile, as well as 22 fertile couples. Clustering of class I HLA (B61 and Cw3) was found with a significant increase in Cw3 in both partners.

The combined effects of carbon monoxide and low temperature on daily variation in hospital admissions for congestive heart failure (CHF) were examined for a 4-year period in Chicago, Illinois. Medicare hospital admissions for CHF were analyzed as a function of the maximum hourly temperature, maximum hourly levels of carbon monoxide (CO), and other criteria pollutants in Chicago for each day of the 4-year period (1986-1989). The regression analyses for the time series were conducted using single and multipollutant models with interaction terms and adjustments for weather, weekly cycles, seasonal effects, and secular trend. The data were also grouped into three temperature ranges, 75 degrees F, and the relationship between CO and CHF admissions was evaluated for each range. For the 4-year time series, the CO level was positively associated with hospital admissions for CHF in the single pollutant and multipollutant models after adjustment for seasonal effects and weather pattern. The relative risks of hospital admissions for CHF in Chicago associated with the 75th percentile of exposure to CO in the high, medium, and low temperature ranges were 1.02 [95% confidence interval (CI), 0.95-1.10], 1.09 (CI, 1.04-1.14), and 1.15 (CI, 1.09-1.22), respectively. In these data, the effect of CO on hospital admissions for CHF was temperature dependent, with the magnitude of the effect increasing with decreasing temperature. This synergy may help to explain the association between ambient CO and CHF admissions demonstrated in other studies. Images Figure 1 Figure 2 Figure 3

In this study, we analyze the recall response to influenza A matrix peptide M1(58-66) restricted by HLA-A2 in one individual and find a strict CDR3 selection as well as a high degree of polyclonality. The TCR β-chain repertoire of memory T cells specific for this Ag system has been shown previously to be constrained by the use of the BV17 family and the I/sRSA/S amino acid motif in the CDR3 region. Our sequence analysis of BV17 TCR from a CTL line showed the repertoire to be highly polyclonal, as 95 distinct CDR3 sequences (clonotypes) were identified expressing this CDR3 motif. The clonotype frequencies showed a power law distribution with an extensive low-frequency tail. The clonotypes present in the high-frequency component of the distribution could be measured directly in the PBMC. This measurement showed that the relative frequencies of these clonotypes before stimulation were similar to their frequencies after culturing. Analysis of short-term cultures showed that the responding clonotypes have a similar ability to proliferate, which is independent of TCR β-chain CDR3 sequence or precursor frequency. These data indicate that the memory T cell repertoire is composed of a surprisingly diverse set of T cell clonotypes with a limited potential for expansion. We propose that the high-frequency component represents T cells that have existed the longest. In keeping with this hypothesis, these clonotypes were measured over a 2-year period, during which their precursor frequency did not change.

All instances of the names of the three major rotavirus strains, G1P[8], G2P[4] and G1P[4] are incorrectly marked with references. The number in brackets should not be separate from the rest of the rotavirus strain, and refers to the rotavirus P type, not a reference number. In the "Compilation of Time Series" under the methods section, a part of the first sentence is missing. The first sentence should read, "To create a time series of counts, we used the date corresponding to the first day of the diarrheal event as the time stamp or the time referencing variable."

Objective: To determine a possible link between herpes simplex virus 1 (HSV) and infertility. Method: A specifically designed polymerase chain reaction with nested primers, was developed and used to test for HSV in 153 men and 20 women attending an infertility clinic. Results: HSV DNA was detected in 37 (24%) out of 153 semen samples and in 11 (55%) out of 20 menstrual blood samples. However, HSV DNA (0%) was not detected in the semen of 16 males with children. A significant association between the evidence for infertility and an HSV positive test was observed in men (Fisher's exact test, p = 0.024), and a stronger effect was found in females after failed in vitro fertilization (Fisher's exact test p = 0.0086). Conclusion: This is the first report of the detection of herpes simplex virus DNA in semen and menstrual blood. Encouraging preliminary results justify antiviral therapy in case of a positive test.