How Drivers of Seasonality in Respiratory Infections May Impact Vaccine Strategy: A Case Study in How Coronavirus Disease 2019 (COVID-19) May Help Us Solve One of Influenza's Biggest Challenges.

Vaccines against seasonal infections like influenza offer a recurring testbed, encompassing challenges in design, implementation, and uptake to combat a both familiar and ever-shifting threat. One of the pervading mysteries of influenza epidemiology is what causes the distinctive seasonal outbreak pattern. Proposed theories each suggest different paths forward in being able to tailor precision vaccines and/or deploy them most effectively. One of the greatest challenges in contrasting and supporting these theories is, of course, that there is no means by which to actually test them. In this communication we revisit theories and explore how the ongoing coronavirus disease 2019 (COVID-19) pandemic might provide a unique opportunity to better understand the global circulation of respiratory infections. We discuss how vaccine strategies may be targeted and improved by both isolating drivers and understanding the immunological consequences of seasonality, and how these insights about influenza vaccines may generalize to vaccines for other seasonal respiratory infections.

Linear Growth Spurts are Preceded by Higher Weight Gain Velocity and Followed by Weight Slowdowns Among Rural Children in Burkina Faso: A Longitudinal Study.

BACKGROUND: The temporal relationship between length (linear) and weight (ponderal) growth in early life is important to support optimal nutrition program design. Studies based on measures of attained size have established that wasting often precedes stunting, but such studies do not capture responsiveness of growth to previous compared with current conditions. As a result, the temporality of linear and ponderal growth relationships remain unclear. OBJECTIVES: We used growth velocity indicators to assess the temporal bidirectional relationships between linear and ponderal growth in children. METHODS: Using monthly anthropometric measurements from 5039 Burkinabè children enrolled at 6 months of age and followed until 28 months from August 2014 to December 2016, we employed multilevel mixed-effects models to investigate concurrent and lagged associations between linear and ponderal growth velocity, controlling for time trends, seasonality, and morbidity. RESULTS: Faster ponderal growth is associated with faster concurrent and subsequent linear growth (0.21-0.72 increase in length velocity z-score per unit increase in weight velocity z-score), while faster linear growth is associated with slower future weight gain (0.009-0.02 decrease in weight velocity z-score per unit increase in length velocity z-score), especially among children 9-14 months. Ponderal growth slows around the same time as peaks in morbidity, followed roughly a month later by slower linear growth. CONCLUSIONS: Use of velocity measures to assess temporal dependencies between linear and ponderal growth demonstrate that the same growth-limiting conditions likely affect both length and weight velocity, that slow ponderal growth likely limits subsequent linear growth, and that linear growth spurts may not be accompanied by sufficient increases in dietary intake to avoid slowdowns in weight gain.

Investigating seasonal patterns in enteric infections: a systematic review of time series methods.

Foodborne and waterborne gastrointestinal infections and their associated outbreaks are preventable, yet still result in significant morbidity, mortality and revenue loss. Many enteric infections demonstrate seasonality, or annual systematic periodic fluctuations in incidence, associated with climatic and environmental factors. Public health professionals use statistical methods and time series models to describe, compare, explain and predict seasonal patterns. However, descriptions and estimates of seasonal features, such as peak timing, depend on how researchers define seasonality for research purposes and how they apply time series methods. In this review, we outline the advantages and limitations of common methods for estimating seasonal peak timing. We provide recommendations improving reporting requirements for disease surveillance systems. Greater attention to how seasonality is defined, modelled, interpreted and reported is necessary to promote reproducible research and strengthen proactive and targeted public health policies, intervention strategies and preparedness plans to dampen the intensity and impacts of seasonal illnesses.

Global seasonal and pandemic patterns in influenza: An application of longitudinal study designs.

The confluence of growing analytic capacities and global surveillance systems for seasonal infections has created new opportunities to further develop statistical methodology and advance the understanding of the global disease dynamics. We developed a framework to characterise the seasonality of infectious diseases for publicly available global health surveillance data. Specifically, we aimed to estimate the seasonal characteristics and their uncertainty using mixed effects models with harmonic components and the δ-method and develop multi-panel visualisations to present complex interplay of seasonal peaks across geographic locations. We compiled a set of 2 422 weekly time series of 14 reported outcomes for 173 Member States from the World Health Organization's (WHO) international influenza virological surveillance system, FluNet, from 02 January 1995 through 20 June 2021. We produced an analecta of data visualisations to describe global travelling waves of influenza while addressing issues of data completeness and credibility. Our results offer directions for further improvements in data collection, reporting, analysis and development of statistical methodology and predictive approaches.

Joint Associations of Multiple Dietary Components With Cardiovascular Disease Risk: A Machine-Learning Approach.

The human diet consists of a complex mixture of components. To realistically assess dietary impacts on health, new statistical tools that can better address nonlinear, collinear, and interactive relationships are necessary. Using data from 1,928 healthy participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort (1985-2006), we explored the association between 12 dietary factors and 10-year predicted risk of atherosclerotic cardiovascular disease (ASCVD) using an innovative approach, Bayesian kernel machine regression (BKMR). Employing BKMR, we found that among women, unprocessed red meat was most strongly related to the outcome: An interquartile range increase in unprocessed red meat consumption was associated with a 0.07-unit (95% credible interval: 0.01, 0.13) increase in ASCVD risk when intakes of other dietary components were fixed at their median values (similar results were obtained when other components were fixed at their 25th and 75th percentile values). Among men, fruits had the strongest association: An interquartile range increase in fruit consumption was associated with -0.09-unit (95% credible interval (CrI): -0.16, -0.02), -0.10-unit (95% CrI: -0.16, -0.03), and -0.11-unit (95% CrI: -0.18, -0.04) lower ASCVD risk when other dietary components were fixed at their 25th, 50th (median), and 75th percentile values, respectively. Using BKMR to explore the complex structure of the total diet, we found distinct sex-specific diet-ASCVD relationships and synergistic interaction between whole grain and fruit consumption.

The Seasonal Microbial Ecology of Plankton and Plankton-Associated Vibrio parahaemolyticus in the Northeast United States.

Microbial ecology studies have proven to be important resources for improving infectious disease response and outbreak prevention. Vibrio parahaemolyticus is an ongoing source of shellfish-borne food illness in the Northeast United States, and there is keen interest in understanding the environmental conditions that coincide with V. parahaemolyticus disease risk, in order to aid harvest management and prevent further illness. Zooplankton and chitinous phytoplankton are associated with V. parahaemolyticus dynamics elsewhere; however, this relationship is undetermined for the Great Bay estuary (GBE), an important emerging shellfish growing region in the Northeast United States. A comprehensive evaluation of the microbial ecology of V. parahaemolyticus associated with plankton was conducted in the GBE using 3 years of data regarding plankton community, nutrient concentration, water quality, and V. parahaemolyticus concentration in plankton. The concentrations of V. parahaemolyticus associated with plankton were highly seasonal, and the highest concentrations of V. parahaemolyticus cultured from zooplankton occurred approximately 1 month before the highest concentrations of V. parahaemolyticus from phytoplankton. The two V. parahaemolyticus peaks corresponded with different water quality variables and a few highly seasonal plankton taxa. Importantly, V. parahaemolyticus concentrations and plankton community dynamics were poorly associated with nutrient concentrations and chlorophyll a, commonly applied proxy variables for assessing ecological health risks and human health risks from harmful plankton and V. parahaemolyticus elsewhere. Together, these statistical associations (or lack thereof) provide valuable insights to characterize the plankton-V. parahaemolyticus dynamic and inform approaches for understanding the potential contribution of plankton to human health risks from V. parahaemolyticus for the Northeast United States. IMPORTANCE The Vibrio-plankton interaction is a focal relationship in Vibrio disease research; however, little is known about this dynamic in the Northeast United States, where V. parahaemolyticus is an established public health issue. We integrated phototactic plankton separation with seasonality analysis to determine the dynamics of the plankton community, water quality, and V. parahaemolyticus concentrations. Distinct bimodal peaks in the seasonal timing of V. parahaemolyticus abundance from phyto- versus zooplankton and differing associations with water quality variables and plankton taxa indicate that monitoring and forecasting approaches should consider the source of exposure when designing predictive methods for V. parahaemolyticus. Helicotheca tamensis has not been previously reported in the GBE. Its detection during this study provides evidence of the changes occurring in the ecology of regional estuaries and potential mechanisms for changes in V. parahaemolyticus populations. The Vibrio monitoring approaches can be translated to aid other areas facing similar public health challenges.

Sustained nutrition impact of a multisectoral intervention program two years after completion.

Progress on the nutrition Sustainable Development Goals has been slow. More attention is needed on the 'sustainable' part, focused on impact lasting beyond programme implementation. To determine sustained impact of a multisectoral nutrition intervention that provided water, sanitation, hygiene, livelihood, health and nutrition support (2013-2015) in eastern Chad, we utilize longitudinal household data collected 2 years (2017) after the intervention ended. Between 2013 and 2015, children (6-59 months) in the multisectoral intervention were less likely to be severely wasted, underweight and had a higher weight-for-height z-score (WHZ) compared with the control. To measure sustained programme impact, we use data on six nutrition indicators from 517 children between 2015 and 2017. We ran three models: a generalized linear model on cross-sectional child cohorts; a mixed-effects model on household panel data; and a mixed-effects model on child panel data. For children who were born during the programme, we saw significant improvement in underweight, weight for age z-scores (WAZs) and height-for-age z-scores (HAZs). Boys 6-23 months born after the end of the programme, on the other hand, were significantly more likely to be underweight or wasted and had lower WHZ and WAZ compared with boys born during the programme and girls born during and after the programme. Corresponding to the literature from sub-Saharan Africa, boys appear to be more vulnerable to malnutrition, which might be why they are more sensitive to programme cessation. Future monitoring, evaluations and research need to consider impact sustainability and that it might not be homogeneous across age and gender.

Ultrafine Particle Number Concentration Model for Estimating Retrospective and Prospective Long-Term Ambient Exposures in Urban Neighborhoods.

Short-term exposure to ultrafine particles (UFP; <100 nm in diameter), which are present at high concentrations near busy roadways, is associated with markers of cardiovascular and respiratory disease risk. To date, few long-term studies (months to years) have been conducted due to the challenges of long-term exposure assignment. To address this, we modified hybrid land-use regression models of particle number concentrations (PNCs; a proxy for UFP) for two study areas in Boston (MA) by replacing the measured PNC term with an hourly model and adjusting for overprediction. The hourly PNC models used covariates for meteorology, traffic, and sulfur dioxide concentrations (a marker of secondary particle formation). We compared model performance against long-term PNC data collected continuously from 9 years before and up to 3 years after the model-development period. Model predictions captured the major temporal variations in the data and model performance remained relatively stable retrospectively and prospectively. The Pearson correlation of modeled versus measured hourly log-transformed PNC at a long-term monitoring site for 9 years prior was 0.74. Our results demonstrate that highly resolved spatial-temporal PNC models are capable of estimating ambient concentrations retrospectively and prospectively with generally good accuracy, giving us confidence in using these models in epidemiological studies.

Beat osteoporosis - nourish and exercise skeletons (BONES): a group randomized controlled trial in children.

BACKGROUND: Lifelong healthy habits developed during childhood may prevent chronic diseases in adulthood. Interventions to promote these habits must begin early. The BONES (Beat Osteoporosis - Nourish and Exercise Skeletons) project assessed whether early elementary school children participating in a multifaceted health behavior change, after-school based intervention would improve bone quality and muscular strength and engage in more bone-strengthening behaviors. METHODS: The 2-year BONES (B) intervention included bone-strengthening physical activity (85 min/week), educational materials (2 days/week), and daily calcium-rich snacks (380 mg calcium/day) delivered by after-school program leaders. BONES plus Parent (B + P) included an additional parent education component. From 1999 to 2004, n = 83 after-school programs (N = 1434 children aged 6-9 years) in Massachusetts and Rhode Island participated in a group randomized trial with two intervention arms (B only, n = 25 programs; B + P, n = 33) and a control arm (C, n = 25). Outcome measures (primary: bone quality (stiffness index of the calcaneus) and muscular strength (grip strength and vertical jump); secondary: bone-strengthening behaviors (calcium-rich food knowledge, preference, and intake; and physical activity level (metabolic equivalent time (MET) score, and weight-bearing factor (WBF) score)) were recorded at baseline, and after years one and two. Analyses followed an intent-to-treat protocol, and focused on individual subjects' trajectories along the three time points adjusting for baseline age and race via a mixed-effects regression framework. Analyses were performed with and without sex stratification. RESULTS: Children in B + P increased bone stiffness compared to C (p = 0.05); No significant changes were observed in muscle strength, food knowledge, or vertical jump. Children in B + P showed significant improvement in their MET and WBF scores compared to C (p < 0.01) with a stronger effect in boys in both B and B + P (all p < 0.01). CONCLUSION: After-school programs, coupled with parental engagement, serving early elementary school children are a potentially feasible platform to deliver bone-strengthening behaviors to prevent osteoporosis in adulthood, with some encouraging bone and physical activity outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00065247. Retrospectively registered. First posted July 22, 2003.

Plasma Response to Deuterium-Labeled Vitamin K Intake Varies by TG Response, but Not Age or Vitamin K Status, in Older and Younger Adults.

Background: Phylloquinone is the primary form of vitamin K in the diet and circulation. Large intra- and interindividual variances in circulating phylloquinone have been partially attributed to age. However, little is known about the nondietary factors that influence phylloquinone absorption and metabolism. Similarly, it is not known if phylloquinone absorption is altered by the individual's existing vitamin K status. Objective: The purpose of this secondary substudy was to compare plasma response with deuterium-labeled phylloquinone intake in older and younger adults after dietary phylloquinone depletion and repletion. Methods: Forty-two older [mean ± SD age: 67.2 ± 8.0 y; body mass index (BMI; in kg/m2): 25.4 ± 4.6; n = 12 men, 9 women] and younger (mean ± SEM age: 31.8 ± 6.6 y; BMI: 25.5 ± 3.3; n = 9 men, 12 women) adults were maintained on sequential 28-d phylloquinone depletion (∼10 µg phylloquinone/d) and 28-d phylloquinone repletion (∼500 µg phylloquinone/d) diets. On the 23rd d of each diet phase, participants consumed deuterated phylloquinone-rich collard greens (2H-phylloquinone). Plasma and urinary outcome measures over 72 h were compared by age group, sex, and dietary phase via 2-factor repeated-measures ANOVA. Results: The plasma 2H-phylloquinone area under the curve (AUC) did not differ in response to phylloquinone depletion or repletion, but was 34% higher in older than in younger adults (P = 0.02). However, plasma 2H-phylloquinone AUC was highly correlated with the serum triglyceride (TG) AUC (r2 = 0.45). After adjustment for serum TG response, the age effect on the plasma 2H-phylloquinone AUC was no longer significant. Conclusions: Plasma 2H-phylloquinone response did not differ between phylloquinone depletion and repletion in older and younger adults. The age effect observed was explained by the serum TG response and was completely attenuated after adjustment. Plasma response to phylloquinone intake, therefore, seems to be a predominantly lipid-driven effect and not dependent on existing vitamin K status. More research is required to differentiate the effect of endogenous compared with exogenous lipids on phylloquinone absorption. This trial was registered at clinicaltrials.gov as NCT00336232.

Incorporating calendar effects to predict influenza seasonality in Milwaukee, Wisconsin.

Social outings can trigger influenza transmission, especially in children and elderly. In contrast, school closures are associated with reduced influenza incidence in school-aged children. While influenza surveillance modelling studies typically account for holidays and mass gatherings, age-specific effects of school breaks, sporting events and commonly celebrated observances are not fully explored. We examined the impact of school holidays, social events and religious observances for six age groups (all ages, ⩽4, 5-24, 25-44, 45-64, ⩾65 years) on four influenza outcomes (tests, positives, influenza A and influenza B) as reported by the City of Milwaukee Health Department Laboratory, Milwaukee, Wisconsin from 2004 to 2009. We characterised holiday effects by analysing average weekly counts in negative binomial regression models controlling for weather and seasonal incidence fluctuations. We estimated age-specific annual peak timing and compared influenza outcomes before, during and after school breaks. During the 118 university holiday weeks, average weekly tests were lower than in 140 school term weeks (5.93 vs. 11.99 cases/week, P < 0.005). The dampening of tests during Winter Break was evident in all ages and in those 5-24 years (RR = 0.31; 95% CI 0.22-0.41 vs. RR = 0.14; 95% CI 0.09-0.22, respectively). A significant increase in tests was observed during Spring Break in 45-64 years old adults (RR = 2.12; 95% CI 1.14-3.96). Milwaukee Public Schools holiday breaks showed similar amplification and dampening effects. Overall, calendar effects depend on the proximity and alignment of an individual holiday to age-specific and influenza outcome-specific peak timing. Better quantification of individual holiday effects, tailored to specific age groups, should improve influenza prevention measures.

Heatwaves and hospitalizations due to hyperthermia in defined climate regions in the conterminous USA.

Heatwaves are one of the deadliest natural disasters that occur annually with thousands of people seeking medical attention. The spatio-temporal synchronization between peaks in disease manifestation and high temperature provides important insights into the seasonal timing of the heatwave and the response it may cause with respect to emergence, severity, and duration. The objectives of this study are to examine the association between hospitalizations due to heat stroke in older adults and heat in the United States (US) and explore synchronization with respect to heatwave sequence, time of arrival, and regional climate. Three large data sets were utilized: daily hospitalization records of the US elderly between 1991 and 2006, annual demographic summaries on Medicare beneficiaries maintained by the Centers for Medicare and Medicaid Services (CMS), and nationwide daily meteorological observations. We modeled seasonal fluctuations in health outcomes, such as the timing and intensity of the seasonal peak in hospitalizations using refined harmonic GLM for eight climatically similar regions. During the 16-year study period, there were 40,019 heat-related hospitalizations (HRH) in the conterminous  US. The rates of HRH varied substantially across eight climatic regions: with the highest rate of 7.05 cases per million residents observed in areas with temperate arid summers and winters (TaTa) and the lowest rate of 0.67-in areas with cold moderately dry summers and arid winters (CdCa), where summer temperatures are about  18.3 °C and 12.1 °C, respectively. We detected 400 heatwaves defined as any day when the night time temperature is above its 90th percentile for the current and previous nights. The first seasonal heatwave in a season resulted in 4274 hospitalizations over 342 heatwave-days: 34.3% of 12,442 hospitalizations occurred in 26% of 1308 heatwave-days. The relative risks of increased HRH associated with the first and second heatwaves were 10.4 (95%CI: 8.5; 12.3) and 11.4 (95%CI: 9.6; 13.3), respectively, indicating the disproportional effects of early heatwave arrivals. The seasonal spike in heat stroke hospitalizations in regions with relatively similar annual temperatures, e.g. in areas with temperate moderately dry summers and winters (TdTa: 12.8 °C) and (TaTa: 11.1 °C) ranged between 4.5 (95%CI: 3.3; 5.5) and 11.0 (95%CI: 8.2; 14.9) cases per million residents, respectively, indicating substantial regional differences. The differences in heat-related hospitalizations and response to heatwaves are substantial among older adults residing in different climate regions of the conterminous US. The disproportionally high response to the early seasonal heatwave deserves special attention, especially in the context of prevention and decision support frameworks.

The use of remotely sensed environmental parameters for spatial and temporal schistosomiasis prediction across climate zones in Ghana.

Schistosomiasis control in sub-Saharan Africa is enacted primarily through preventive chemotherapy. Predictive models can play an important role in filling knowledge gaps in the distribution of the disease and help guide the allocation of limited resources. Previous modeling approaches have used localized cross-sectional survey data and environmental data typically collected at a discrete point in time. In this analysis, 8 years (2008-2015) of monthly schistosomiasis cases reported into Ghana's national surveillance system were used to assess temporal and spatial relationships between disease rates and three remotely sensed environmental variables: land surface temperature (LST), normalized difference vegetation index (NDVI), and accumulated precipitation (AP). Furthermore, the analysis was stratified by three major and nine minor climate zones, defined using a new climate classification method. Results showed a downward trend in reported disease rates (~ 1% per month) for all climate zones. Seasonality was present in the north with two peaks (March and September), and in the middle of the country with a single peak (July). Lowest disease rates were observed in December/January across climate zones. Seasonal patterns in the environmental variables and their associations with reported schistosomiasis infection rates varied across climate zones. Precipitation consistently demonstrated a positive association with disease outcome, with a 1-cm increase in rainfall contributing a 0.3-1.6% increase in monthly reported schistosomiasis infection rates. Generally, surveillance of neglected tropical diseases (NTDs) in low-income countries continues to suffer from data quality issues. However, with systematic improvements, our approach demonstrates a way for health departments to use routine surveillance data in combination with publicly available remote sensing data to analyze disease patterns with wide geographic coverage and varying levels of spatial and temporal aggregation.