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.

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.

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

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.

Leptin, body composition and bone mineral density in premenopausal women.

Body weight is known to be associated with bone mass, however, it is unclear whether body composition, as reflected by the percent of total weight that is fat tissue (%fat), is associated with bone mass independently of weight. Fat tissue is metabolically active, and hormonal factors may mediate an association of %fat with bone mass. Leptin, a hormone produced in fat tissue, has recently been shown to be inversely related to bone mass in mice, but whether it is related to human bone mass is uncertain. We sought to investigate the associations of %fat and of serum leptin concentration with bone mineral density (BMD) in a cohort of 153 premenopausal women. BMD measurements of the total hip, lumbar spine and total body as well as body composition were measured by dual energy X-ray absorptiometry (DXA). Serum leptin levels were established using a commercial competitive binding assay. Individually, body weight, %fat and leptin were each positively associated with BMD at all three sites. However, when we examined BMD either as a function of both body weight and %fat together, or as a function of both body weight and leptin together, we found that for a given body weight, BMD appeared to be inversely associated with %fat and similarly appeared to be inversely associated with leptin. When BMD was examined as a function of %fat and leptin together, we found that for a given %fat, leptin appeared to be inversely associated with BMD. In summary, the results of this study suggest that for a given body weight, a higher proportion of fat and a higher serum leptin concentration have negative associations with bone mass in premenopausal women.

Expert opinion on body mass index percentiles for figure drawings at menarche.

We contacted clinicians and researchers who work in the area of childhood obesity to obtain a reasonable estimate of body mass index (BMI) percentile at menarche associated with a series of widely used figure drawings. Forty of 108 subscribers to the electronic listserv of the Pediatric Obesity Interest Group of the North American Association for the Study of Obesity responded to a request to estimate the BMI percentile at menarche for each of seven drawings. Median BMI percentile values ranged from three to 98 and means from 4.0 to 97.6, with the greatest agreement at the high end and the poorest agreement in the central part of the range. This approach may be useful in situations where weight and height are not readily recalled.

Recall of early menstrual history and menarcheal body size: after 30 years, how well do women remember?

The validity of recall of early menstrual characteristics is of interest because of their putative role in the etiology of breast cancer and other diseases. A retrospective follow-up of the Newton Girls Study (1965-1975) provided an opportunity to assess the accuracy and precision of recall of several early menstrual characteristics. In 1998-1999, 57 percent of the original 793 Newton Girls Study participants completed a mailed questionnaire to assess the accuracy of recall for age and body size at menarche, usual cycle length during the first 2 years, and age at regularity. Recalled and original age at menarche were highly correlated (r = 0.79, p < 0.001). The body mass index percentile at menarche was well correlated with recalled body size at menarche (r = 0.61, p < 0.001), but with some evidence of systematic bias. Overall, a woman's recall of menarcheal age and body size was better than recall of cycle length and occurrence of regularity. The failure to identify certain menstrual characteristics as exposures for subsequent disease may reflect limitations in the accuracy and precision of the recalled measures.

Possible undetected outbreaks of cryptosporidiosis in areas of the north west of England supplied by an unfiltered surface water source.

We report a ten-year retrospective analysis of laboratory reports of cryptosporidium infection in the North West of England. Weekly report data from six health authorities known to have been affected by outbreaks associated with a single supply were compared with data from other health authorities in the North West. Following graphical representation of report rates, it would appear that outbreaks in the six health authorities were considerably more common than the average recorded in the national outbreak surveillance system.

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.

[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.

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.

Survival and failure to thrive in the SIV-infected juvenile rhesus monkey.

In AIDS patients, wasting in adults and failure to thrive in children are common and devastating problems. Weight loss in rhesus macaques infected with simian immunodeficiency virus (SIV) has not been well characterized. The purpose of this study was to determine growth curves in SIV-infected juvenile macaques to determine the effects of SIV infection on body weight and growth. Medical records of seven juvenile male SIV-infected macaques were retrospectively reviewed to determine body weights, survival time, CD4 count, and viral load. Mean age and body weight at the time of inoculation were 63.3 weeks and 2.4 kg, respectively. Mean survival was 73.7 weeks, and mean body weight at the time of death was 3.0 kg, whereas the published mean body weight for this age of male rhesus macaque is 4.1 kg. Compared with the linear growth pattern of normal animals, the growth pattern for the SIV-infected animals exhibited strong nonlinearity with an inflection point at the mean survival of 74 weeks. After this time point, the discrepancy between growth curves for infected and healthy animals increased at a greater rate. Body weight correlated inversely with viral load (r = -0.368; p = .003) but there was no correlation between body weight and CD4 count. The results of this study suggest that failure to thrive is a consequence of SIV infection and may be related to severity of infection.