The shift in seasonality of legionellosis in the USA.

According to the Centers for Disease Control and Prevention (CDC), from 2000 to 2014, reported cases of legionellosis per 100 000 population increased by 300% in the USA, although reports on disease seasonality are inconsistent. Using two national databases, we assessed seasonal patterns of legionellosis in the USA. We created a monthly time series from 1993 to 2015 of reported cases of legionellosis from the CDC, and from 1997 to 2006 of medical claims of legionellosis-related hospitalisation in older adults from the Centers for Medicaid and Medicare Services (CMS). We split the study time interval into two segments (before and after 2003), and applied a Poisson harmonic regression model to each dataset and each segment. The time series of monthly counts exhibited a significant shift of seasonal peaks from mid-September (9.676 ± 0.164 months) before 2003 to mid-August (8.452 ± 0.042 months) after 2003, along with an alarming increase in the amplitude of seasonal peaks in both CDC and CMS data. The lowest monthly reported cases of legionellosis in 2015 (281) exceed the maximum value reported before 2003 (206). We also observed a discrepancy between CDC and CMS data, suggesting that not all cases of legionellosis diagnosed by hospital-based laboratories were reported to the CDC. Improved reporting of legionellosis is required to better inform the public and organise disease prevention.

Seasonality and within-subject clustering of rotavirus infections in an eight-site birth cohort study.

Improving understanding of the pathogen-specific seasonality of enteric infections is critical to informing policy on the timing of preventive measures and to forecast trends in the burden of diarrhoeal disease. Data obtained from active surveillance of cohorts can capture the underlying infection status as transmission occurs in the community. The purpose of this study was to characterise rotavirus seasonality in eight different locations while adjusting for age, calendar time and within-subject clustering of episodes by applying an adapted Serfling model approach to data from a multi-site cohort study. In the Bangladesh and Peru sites, within-subject clustering was high, with more than half of infants who experienced one rotavirus infection going on to experience a second and more than 20% experiencing a third. In the five sites that are in countries that had not introduced the rotavirus vaccine, the model predicted a primary peak in prevalence during the dry season and, in three of these, a secondary peak during the rainy season. The patterns predicted by this approach are broadly congruent with several emerging hypotheses about rotavirus transmission and are consistent for both symptomatic and asymptomatic rotavirus episodes. These findings have practical implications for programme design, but caution should be exercised in deriving inferences about the underlying pathways driving these trends, particularly when extending the approach to other pathogens.

Environmental predictors of diarrhoeal infection for rural and urban communities in south India in children and adults.

Diarrhoeal 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 (<5 years) residing in two semi-urban slums and three villages were visited weekly for 12-18 months to monitor gastrointestinal morbidity. Households were surveyed at baseline to obtain information on environmental and behavioural factors relevant to diarrhoea. There were 258 diarrhoeal episodes during the follow-up period, resulting in an overall incidence rate of 0·12 episodes/person-year. Incidence and longitudinal prevalence rates of diarrhoea were twofold higher in the slums compared to rural communities (P < 0·0002). Regardless of study site, diarrhoeal incidence was highest in infants (<1 year) at 1·07 episodes/person-year, and decreased gradually with increasing age. Increasing diarrhoeal rates were associated with presence of children (<5 years), domesticated animals and low socioeconomic status. In rural communities, open-field defecation was associated with diarrhoea in young children. This study demonstrates the contribution of site-specific environmental and behavioural factors in influencing endemic rates of urban and rural diarrhoea in a region with highly contaminated drinking water.

Pneumonia and influenza hospitalization in HIV-positive seniors.

HIV-positive persons and the elderly have increased risk for influenza-related complications, including pneumonia. Using claims data for pneumonia and influenza (P&I) hospitalization in the USA, we described the temporo-demographic trends and in-patient case-fatality in persons aged ≥ 65 years by HIV status. Our results showed a near doubling in the fraction of P&I admissions representing HIV-positive persons between 1991 and 2004 [relative risk (RR) 1·95, 95% confidence interval (CI) 1·80-2·13]. HIV-positive adults were younger (70·3 vs. 79·9 years, P<0·001), and had higher case-fatality (18·0% vs. 12·6%, P<0·001). Adjusting for other variables, case-fatality decreased by 5·8% in HIV-positive persons with the availability of highly active antiretroviral therapy (P=0·032). However, HIV-positive seniors were still 51% more likely to die during hospitalization than HIV-negative persons in 2004 (OR 1·51, 95% CI 1·23-1·85). HIV-infected persons represent a growing fraction of the elderly population hospitalized with P&I. Additional measures are needed to reduce case-fatality associated with P&I in this population.

Recent diarrhea is associated with elevated salivary IgG responses to Cryptosporidium in residents of an eastern Massachusetts community.

BACKGROUND: Serological data suggest that Cryptosporidium infections are common but underreported. The invasiveness of blood sampling limits the application of serology in epidemiological surveillance. We pilot-tested a non-invasive salivary anti-Cryptosporidium antibody assay in a community survey involving children and adults. MATERIALS AND METHODS: Families with children were recruited in a Massachusetts community in July; symptoms data were collected at 3 monthly follow-up mail surveys. One saliva sample per person (n = 349) was collected via mail, with the last survey in October. Samples were analyzed for IgG and IgA responses to a recombinant C. hominis gp15 sporozoite protein using a time-resolved fluorometric immunoassay. Log-transformed assay results were regressed on age using penalized B-splines to account for the strong age-dependence of antibody reactions. Positive responses were defined as fluorescence values above the upper 99% prediction limit. RESULTS: Forty-seven (13.5%) individuals had diarrhea without concurrent respiratory symptoms during the 3-month-long follow-up; eight of them had these symptoms during the month prior to saliva sampling. Two individuals had positive IgG responses: an adult who had diarrhea during the prior month and a child who had episodes of diarrhea during each survey month (Fisher's exact test for an association between diarrhea and IgG response: p = 0.0005 for symptoms during the prior month and p = 0.02 for symptoms during the entire follow-up period). The child also had a positive IgA response, along with two asymptomatic individuals (an association between diarrhea and IgA was not significant). CONCLUSION: These results suggest that the salivary IgG specific to Cryptosporidium antigens warrants further evaluation as a potential indicator of recent infections.

Trends for influenza and pneumonia hospitalization in the older population: age, period, and cohort effects.

Birth cohort has been shown to be related to morbidity and mortality from other diseases and conditions, yet little is known about the potential for birth cohort in its relation to pneumonia and influenza (P&I) outcomes. This issue is particularly important in older adults, who experience the highest disease burden and most severe complications from these largely preventable diseases. The objective of this analysis is to assess P&I patterns in US seniors with respect to age, time, and birth cohort. All Medicare hospitalizations due to P&I (ICD-9CM codes 480-487) were abstracted and categorized by single-year of age and influenza year. These counts were then divided by intercensal estimates of age-specific population levels extracted from the US Census Bureau to obtain age- and season-specific rates. Rates were log-transformed and linear models were used to assess the relationships in P&I rates and age, influenza year, and cohort. The increase in disease rates with age accounted for most of the variability by age and influenza season. Consistent relationships between disease rates and birth cohorts remained, even after controlling for age. Seasonal associations were stronger for influenza than for pneumonia. These findings suggest that there may be a set of unmeasured characteristics or events people of certain ages experienced contemporaneously that may account for the observed differences in P&I rates in birth cohorts. Further understanding of these circumstances and those resulting age and cohort groups most vulnerable to P&I may help to target health services towards those most at risk of disease.

Lower extremity muscle mass predicts functional performance in mobility-limited elders.

OBJECTIVES: This study examined the influence of lower extremity body composition and muscle strength on the severity of mobility-disability in community-dwelling older adults. METHODS: Fifty-seven older males and females (age 74.2 +/- 7 yrs; BMI 28.9 +/- 6 kg/m2) underwent an objective assessment of lower extremity functional performance, the Short Physical Performance Battery test (SPPB). Participants were subsequently classified as having moderate (SPPB score 7: n = 38) or severe mobility impairments (SPPB score

CD4+ and CD8+ circulating alpha/beta T-cell repertoires are equally complex and are characterized by different levels of steady-state TCR expression.

The repertoire complexity of CD4+ and CD8+ T cells was measured in three healthy blood donors for a number of TCR BV gene families by TCR spectratyping. This method subdivides V family-specific PCR products based on CDR3 length. Genomic DNA was analyzed to determine the distribution of the cells bearing particular V-J rearrangements. cDNA was analyzed to measure the levels of transcripts arising from those same cells. The complexity and distribution of T cells in each lineage were equal for most BV families. Certain families showed frequent skewing in CD8 cells. Analysis of the intensity profiles of RNA versus DNA spectratypes indicated that in general, there is a constant ratio of transcript per cell for all rearranged sizes within a particular family. This ratio appeared higher in CD4 cells. Thus, steady state levels of TCR mRNA were measured and found to be higher in CD4+ than in CD8+ cells.

Carbon monoxide and hospital admissions for congestive heart failure: evidence of an increased effect at low temperatures.

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, <40 degrees, 40 degrees-75 degrees, and >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.

Tutorial in Biostatistics: Evaluating the impact of 'critical periods' in longitudinal studies of growth using piecewise mixed effects models.

Recent developments in modern multivariate methods provide applied researchers with the means to address many important research questions that arise in studies with repeated measures data collected on individuals over time. One such area of applied research is focused on studying change associated with some event or critical period in human development. This tutorial deals with the use of the general linear mixed model for regression analysis of correlated data with a two-piece linear function of time corresponding to the pre- and post-event trends. The model assumes a continuous outcome is linearly related to a set of explanatory variables, but allows for the trend after the event to be different from the trend before it. This task can be accomplished using a piecewise linear random effects model for longitudinal data where the response depends upon time of the event. A detailed example that examines the influence of menarche on changes in body fat accretion will be presented using data from a prospective study of 162 girls measured annually from approximately age 10 until 4 years post menarche.

Presence of HSV-1 DNA in semen and menstrual blood.

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.

Childhood asthma surveillance using computerized billing records: a pilot study.

OBJECTIVE: This paper describes a pilot project to develop and implement a low-cost system for ongoing surveillance of childhood asthma in Milwaukee County, Wisconsin. METHODS: The authors organized a planning workshop to solicit information and ideas for an asthma surveillance system, bringing together national experts with Milwaukee professionals and community representatives involved in the prevention and treatment of asthma. Based on recommendations from the workshop, a pilot surveillance project was implemented in Milwaukee County using records of emergency room visits and hospital admissions for asthma abstracted from the computerized billing records of the Children's Hospital of Wisconsin (CHW), retrospectively for 1993 and prospectively for 1994. Retrospective data were also sought from the other hospital emergency departments in Milwaukee County to evaluate the representativeness of the CHW data. Surveillance data were used to evaluate utilization of care by patient subgroups and to describe temporal patterns in emergency room visits. RESULTS: Of the emergency department visits for asthma in Milwaukee County in 1993, CHW accounted for 94% among infants less than 1 year of age, 89% among children ages 1 through 5 years, and only 59% among children between the ages of 6 and 18 years. In 1994, the 7% of asthmatic children with repeat hospital admissions accounted for 38% of all hospital admissions for asthma and the 20% with repeat emergency department visits accounted for 50% of all emergency visits. Emergency visits for asthma showed clear seasonality, with a peak in the fall and a smaller peak in the spring. CONCLUSIONS: Computerized medical billing data provide an opportunity for asthma surveillance at a relatively low cost. The data obtained are useful for tracking trends in exacerbations of asthma and the use of medical services for asthma care and should prove valuable in targeting interventions.

Use of passive surveillance data to study temporal and spatial variation in the incidence of giardiasis and cryptosporidiosis.

OBJECTIVE: The goal of this study was to evaluate temporal and spatial variations in the reporting of cases of giardiasis and cryptosporidiosis to a passive surveillance system, and to assess the relationship of those variations to source of drinking water, adjusting for socioeconomic variables. METHODS: The authors analyzed temporal and spatial patterns for 4,058 cases of giardiasis and 230 cases of cryptosporidiosis reported to the Massachusetts Department of Public Health for 1993-1996. They linked each reported case to a database containing information on source of residential water supply and socioeconomic characteristics and evaluated the association between these factors and reporting rates using regression techniques. RESULTS: Reports of giardiasis and cryptosporidiosis were highest for the mixed unfiltered drinking water supply category. Reports of giardiasis were associated with income levels. Increases in reporting for both giardiasis and cryptosporidiosis were seen in summer to early fall. During a suspected outbreak of cryptosporidiosis n the city of Worcester in 1995, a significant increase in reported cases was also observed in the Boston metropolitan area. Following the suspected outbreak, weekly giardiasis rates increased slightly in Worcester and the Boston metropolitan area, while reporting of cryptosporidiosis increased dramatically. CONCLUSIONS: Consistently collected passive surveillance data have the potential to provide valuable information on the temporal variation of disease incidence as well as geographic factors. However, passive surveillance data, particularly in the initial period of surveillance, may be highly sensitive to patterns of diagnosis and reporting and should be interpreted with caution.

[Effect of population density on ecological characteristics of the grass moth Loxostege sticticalis L. (Lepidoptera: Pyralidae) in the gradation cycle]. / Deistvie plotnosti populiatsii na ékologicheskie kharakteristiki lugovogo motyl'ka Loxostege sticticalis L. (Lepidoptera: Pyralidae) v gradatsionnom tsikle.

We continued to study the diversity of responses of the grass moth Loxostege sticticalis L. to variations of density. We estimated the dynamics of the internal state of individuals and considered the influence of the population prehistory on ecological characteristics of the phytophage. In experiments on studying the structure of flower forms of the larval stage, we showed the dependence of the parameters of the internal state of individuals on prehistory, specifically on the conditions of life and type of individuals of the preceding generation. At the same time, comparison of the experimental results of 1991 and 1994 revealed a drift of the parameters of the reaction to variations in the grass moth population density by the structure of the larval flower forms and actual fertility of the imago. On the whole, the data obtained suggests that the studied species is characterized by a complex system of endogenous mechanisms underlying the regulation of numbers. The dynamics of environmental parameters is mediated by a cascade of endogenous rearrangements, as a result of which transition from depression to mass reproduction is realized through succession of the types of individuals in the population, when instead of a single phase, the flock phase starts to dominate.

Deviations in influenza seasonality: odd coincidence or obscure consequence?

In temperate regions, influenza typically arrives with the onset of colder weather. Seasonal waves travel over large spaces covering many climatic zones in a relatively short period of time. The precise mechanism for this striking seasonal pattern is still not well understood, and the interplay of factors that influence the spread of infection and the emergence of new strains is largely unknown. The study of influenza seasonality has been fraught with problems. One of these is the ever-shifting description of illness resulting from influenza and the use of both the historical definitions and new definitions based on actual isolation of the virus. The compilation of records describing influenza oscillations on a local and global scale is massive, but the value of these data is a function of the definitions used. In this review, we argue that observations of both seasonality and deviation from the expected pattern stem from the nature of this disease. Heterogeneity in seasonal patterns may arise from differences in the behaviour of specific strains, the emergence of a novel strain, or cross-protection from previously observed strains. Most likely, the seasonal patterns emerge from interactions of individual factors behaving as coupled resonators. We emphasize that both seasonality and deviations from it may merely be reflections of our inability to disentangle signal from noise, because of ambiguity in measurement and/or terminology. We conclude the review with suggestions for new promising and realistic directions with tangible consequences for the modelling of complex influenza dynamics in order to effectively control infection.

Change in leptin, body composition and other hormones around menarche--a visual representation.

AIM: To present a visual representation of changes in body composition, leptin, insulin, estradiol and follicular stimulating hormone (FSH) levels in relation to menarche in girls. METHODS: Participants were a subset of healthy girls (n = 108) enrolled in a longitudinal study of growth and development conducted at the General Clinical Research Center at the Massachusetts Institute of Technology (MIT). Participants were seen annually from before menarche until 4 years postmenarche for measures of body composition and serum levels of leptin, insulin, estradiol and FSH. Body composition was determined by bioelectrical impedance. Standardized body composition and hormone levels were smoothed and plotted relative to menarche to visualize patterns of change. RESULTS: At menarche, the mean percentage body fat (%BF) of girls was 24.6% (SD = 4.1%) after menarche %BF was approximately 27%. Leptin levels averaged 8.4 ng/mL (SD = 4.6) at menarche and were approximately 12 ng/mL after menarche. Changes in leptin levels closely paralleled changes in %BF. Insulin, estradiol and FSH levels followed expected patterns relative to menarche. Leptin began rising closer to menarche than did insulin or the other sex hormones. CONCLUSION: We provide a visual presentation of hormonal and body composition changes occurring throughout the pubertal period in girls which may be useful in generating new hypotheses related to the timing of menarche.

Precision of Lunar Achilles+ bone quality measurements: time dependency and multiple machine use in field studies.

Qualitative ultrasound (QUS) is a portable, safe and relatively inexpensive technique used to obtain information on bone mineral quality in adults and children. QUS measures bone stiffness index (SI) through the incorporation of speed of sound (SOS) and broadband ultrasound attenuation (BUA). QUS technology may prove to be extremely useful in field research where more than one machine is used over different periods of time. 13 adults (27.6+/-4.6 years old) were recruited to determine the internal stability of two Lunar Achilles+ QUS machines (Lunar1, Lunar2), as well as the repeatability in bone stiffness measures between the two machines over time. Triplicate measurements of the calcaneus were taken within the same day (n = 258) and at 1 week (n = 120), 6 months (n = 54) and 1 year (n = 18) apart to determine the time-dependent repeatability. Using paired t-tests and separate mixed effects models, there were no differences reported in SI, SOS or BUA values within one machine, or between two machines over these short- and long-term time-frames. These results indicate that QUS machines are internally consistent and different machines may be used over time to provide reliable measurements of changes in bone quality.

Seasonality in six enterically transmitted diseases and ambient temperature.

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 (approximately 40 days, P<0.02). The proposed approach provides a detailed quantification of seasonality that enabled us to detect significant differences in the seasonal peaks of enteric infections which would have been lost in an analysis using monthly or weekly cumulative information. This highly relevant to disease surveillance approach can be used to generate and test hypotheses related to disease seasonality and potential routes of transmission with respect to environmental factors.

Ambient air pollution and hospitalization for congestive heart failure among elderly people in seven large US cities.

OBJECTIVES: Preexisting data sets were used to investigate the association between hospital admissions for congestive heart failure and air pollutants. METHODS: Medicare hospital admissions data, ambient air pollution monitoring data, and meteorological data were used to create daily values of hospital admissions for congestive heart failure, maximum hourly temperature, and maximum hourly levels of carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone. Data were compiled for each of seven cities (Chicago, Detroit, Houston, Los Angeles, Milwaukee, New York, and Philadelphia) for 1986 through 1989. Single-pollutant and multipollutant models with adjustments for temperature, seasonal effects, and weekly cycles were used in conducting negative binomial regression analyses. RESULTS: Ambient carbon monoxide levels were positively associated with hospital admissions for congestive heart failure in the single-pollutant and multipollutant models for each of the seven cities. The relative risk of hospital admission for congestive heart failure associated with an increase of 10 ppm in carbon monoxide ranged from 1.10 in New York to 1.37 in Los Angeles. CONCLUSIONS: Hospital admissions for congestive heart failure exhibited a consistent association with daily variations in ambient carbon monoxide. This association was independent of season, temperature, and other major gaseous pollutants.