Sun protection to improve vaccine effectiveness in children in a high ambient ultraviolet radiation and rural environment: an intervention study.

BACKGROUND: Vaccination is a mainstay of preventive healthcare, reducing the incidence of serious childhood infections. Ecological studies have demonstrated an inverse association between markers of high ambient ultraviolet (UV) radiation exposure (e.g., sunny season, low latitude of residence) and reduction in the vaccination-associated immune response. Higher sun exposure on the day prior to and spanning the day of vaccination has been associated with a reduced antigen-specific immune response independent of skin pigmentation. The South African Department of Health's Expanded Programme on Immunisation provides free vaccinations in government primary health care clinics. In some areas, these clinics may have only a small waiting room and patients wait outside in full sun conditions. In rural areas, patients may walk several kilometres to and from the clinic. We hypothesised that providing sun protection advice and equipment to mothers of children (from 18 months) who were waiting to be vaccinated would result in a more robust immune response for those vaccinated. METHODS: We conducted an intervention study among 100 children receiving the booster measles vaccination. We randomised clinics to receive (or not) sun protection advice and equipment. At each clinic we recorded basic demographic data on the child and mother/carer participants, their sun exposure patterns, and the acceptability and uptake of the provided sun protection. At 3-4 weeks post-vaccination, we measured measles IgG levels in all children. DISCUSSION: This is the first intervention study to assess the effect of sun protection measures on vaccine effectiveness in a rural, real-world setting. The novel design and rural setting of the study can contribute much needed evidence to better understand sun exposure and protection, as well as factors determining vaccine effectiveness in rural Africa, and inform the design of immunisation programmes. (TRN PACTCR201611001881114, 24 November 2016, retrospective registration).

Comparing the effects of sun exposure and vitamin D supplementation on vitamin D insufficiency, and immune and cardio-metabolic function: the Sun Exposure and Vitamin D Supplementation (SEDS) Study.

BACKGROUND: Adults living in the sunny Australian climate are at high risk of skin cancer, but vitamin D deficiency (defined here as a serum 25-hydroxyvitamin D (25(OH)D) concentration of less than 50 nmol/L) is also common. Vitamin D deficiency may be a risk factor for a range of diseases. However, the optimal strategies to achieve and maintain vitamin D adequacy (sun exposure, vitamin D supplementation or both), and whether sun exposure itself has benefits over and above initiating synthesis of vitamin D, remain unclear. The Sun Exposure and Vitamin D Supplementation (SEDS) Study aims to compare the effectiveness of sun exposure and vitamin D supplementation for the management of vitamin D insufficiency, and to test whether these management strategies differentially affect markers of immune and cardio-metabolic function. METHODS/DESIGN: The SEDS Study is a multi-centre, randomised controlled trial of two different daily doses of vitamin D supplementation, and placebo, in conjunction with guidance on two different patterns of sun exposure. Participants recruited from across Australia are aged 18-64 years and have a recent vitamin D test result showing a serum 25(OH)D level of 40-60 nmol/L. DISCUSSION: This paper discusses the rationale behind the study design, and considers the challenges but necessity of data collection within a non-institutionalised adult population, in order to address the study aims. We also discuss the challenges of participant recruitment and retention, ongoing engagement of referring medical practitioners and address issues of compliance and participant retention. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry: ACTRN12613000290796 Registered 14 March 2013.

Keyhole limpet haemocyanin - a model antigen for human immunotoxicological studies.

Immunization with a T-cell dependent antigen has been promoted as a reliable and sensitive tool for assessing the influence of putative immunotoxic exposures or agents on immune function. Keyhole limpet haemocyanin (KLH) is a very large, copper-containing protein molecule derived from the haemolymph of the inedible mollusc, Megathura crenulata. KLH is a highly immunogenic T-cell dependent antigen that is used increasingly in immunotoxicological studies, particularly in those involving animals. This report systematically reviews the human clinical studies that have used trans-cutaneous KLH immunization for assessment of the influence of various physiological and disease states and exposures on immune function over the last 20 years (1994-2013). These studies varied in their immunization protocols, formulation of KLH, dose, site and route of administration and immunoassay platforms developed to assess KLH-specific responses. KLH immunization has been well tolerated with only mild to moderate adverse effects reported. Though very promising as a model antigen candidate in immunotoxicology research, more work on standardizing immunization and immunoassay protocols is required.

Vitamin D deficiency and risk for rheumatic diseases: an update.

PURPOSE OF REVIEW: The role of vitamin D in situations other than calcium homeostasis and bone health has become very topical. It is apparent that vitamin D has significant effects on the immune system and as such may contribute to the pathogenesis of autoimmune disease. This review examines the evidence-to-date that vitamin D has a role in immune-mediated rheumatic disorders. RECENT FINDINGS: Low vitamin D status is reported in many inflammatory rheumatic conditions. In some this extends to an association with disease activity. Vitamin D acts on a number of cells involved in both innate and acquired immunity biasing the adaptive immune system away from Th17 and Th1, towards Th2 and Tregs. Deficiency accordingly could encourage autoimmunity. Direct evidence for this plausible mechanism in specific diseases remains largely to be demonstrated. To date, there is a dearth of controlled trials of vitamin D in prophylaxis or therapy. SUMMARY: Vitamin D deficiency may well be an important factor in autoimmune rheumatic disease, including initial disease development and worsening the disease once present. This is testable and there is a pressing need for therapeutic studies.

Physical and Mental Health Effects of Bushfire and Smoke in the Australian Capital Territory 2019-20.

The 2019-20 bushfire season in south-eastern Australia was one of the most severe in recorded history. Bushfire smoke-related air pollution reached hazardous levels in major metropolitan areas, including the Australian Capital Territory (ACT), for prolonged periods of time. Bushfire smoke directly challenges human health through effects on respiratory and cardiac function, but can also indirectly affect health, wellbeing and quality of life. Few studies have examined the specific health effects of bushfire smoke, separate from direct effects of fire, and looked beyond physical health symptoms to consider effects on mental health and lifestyle in Australian communities. This paper describes an assessment of the health impacts of this prolonged exposure to hazardous levels of bushfire smoke in the ACT and surrounding area during the 2019-20 bushfire season. An online survey captured information on demographics, health (physical and mental health, sleep) and medical advice seeking from 2,084 adult participants (40% male, median age 45 years). Almost all participants (97%) experienced at least one physical health symptom that they attributed to smoke, most commonly eye or throat irritation, and cough. Over half of responders self-reported symptoms of anxiety and/or feeling depressed and approximately half reported poorer sleep. Women reported all symptoms more frequently than men. Participants with existing medical conditions or poorer self-rated health, parents and those directly affected by fire (in either the current or previous fire seasons) also experienced poorer physical, mental health and/or sleep symptoms. Approximately 17% of people sought advice from a medical health practitioner, most commonly a general practitioner, to manage their symptoms. This study demonstrated that prolonged exposure to bushfire smoke can have substantial effects on health. Holistic approaches to understanding, preventing and mitigating the effects of smoke, not just on physical health but on mental health, and the intersection of these, is important. Improved public health messaging is needed to address uncertainty about how individuals can protect their and their families health for future events. This should be informed by identifying subgroups of the population, such as those with existing health conditions, parents, or those directly exposed to fire who may be at a greater risk.

Spatial clusters of Clostridium difficile infection and an association with neighbourhood socio-economic disadvantage in the Australian Capital Territory, 2004-2014.

BACKGROUND: In Australia, rates of Clostridium difficile infection (CDI) in all States and Territories have increased significantly since mid-2011, with rates of infection increasing faster in the community setting than within hospitals. Knowledge about the risk factors for CDI is essential to determine the risk of community outbreaks of CDI and to design interventions that reduce those risks. METHODS: We examine the role of neighbourhood socio-economic disadvantage, demography and testing practices on spatial patterns in CDI incidence in the Australian Capital Territory (ACT). Data on all tests conducted for CDI, including postcode of residence, were obtained from January 2004-December 2014. Distribution of age groups and the neighbourhood Index of Relative Socio-economic Advantage Disadvantage (IRSAD) were obtained from the Australian Bureau of Statistics 2011 National Census data. A Bayesian spatial conditional autoregressive model was fitted at the postcode level to quantify the relationship between CDI and socio-demographic factors. To identify CDI hotspots, exceedance probabilities were set at a threshold of twice the estimated relative risk. RESULTS: After controlling for spatial patterns in testing practices, area-level socio-economic advantage (IRSAD) (RR = 0.74, 95% CI 0.57, 0.94) was inversely associated with CDI. Three postcodes had a high probability (0.8-1.0) of excess risk of diagnosed CDI. CONCLUSION: We demonstrate geographic variations in CDI in the ACT with a positive association of CDI with neighbourhood socioeconomic disadvantage and identify areas with a high probability of elevated risk compared with surrounding communities. These findings provide further evidence to inform a targeted response to reduce CDI risk.

Effect of A Sun Protection Intervention on the Immune Response to Measles Booster Vaccination in Infants in Rural South Africa.

The incidence of many serious childhood infections can be reduced by vaccination. High sun exposure at the time of vaccination has been associated with a reduced antigen-specific immune response. We hypothesized that providing sun protection advice and equipment to mothers of children who were waiting to be vaccinated would result in a more robust immunization response. We conducted a pilot study in 2015/2016 (data analyzed in 2017-2018) among 98 Black African children (~18 months of age) receiving the booster measles vaccination at two clinics in South Africa. Clinics were randomized to receive (or not) sun protection advice and equipment. We recorded demographic information on children and mothers and data on the child's usual sun exposure. At approximately 4 weeks' postmeasles vaccination, we measured measles immunoglobulin G levels in children. All children with blood results (n = 87, 89%) across both groups had antibody titers higher than 200 mIU mL-1 which was considered the protective antibody concentration. There was no statistically significant difference in titers between groups: geometric difference in mean titers 1.13 mIU mL-1 (95% CI 0.85, 1.51; P = 0.39) and 1.38 mIU mL-1 (95% CI 0.90, 2.11, P = 0.14) for unadjusted and adjusted analyses, respectively. This study demonstrated that a sun protection intervention study could be performed in a developing-world pediatric vaccination setting. Although the sun protection intervention around the time of vaccination was not associated with a higher antibody level, given the potential importance of such an effect, a larger study should be considered.

Exposure to Solar UVR Suppresses Cell-Mediated Immunization Responses in Humans: The Australian Ultraviolet Radiation and Immunity Study.

Animal and human studies show that exposure to solar-simulated UVR is immunomodulatory. Human studies that used natural sun exposure and controlled for confounding are rare. We immunized 217 healthy adults (age range = 18-40 years) with a T-cell-dependent antigen, keyhole limpet hemocyanin, and measured personal clothing-adjusted UVR exposure (for 5 days before and after immunization), lifetime cumulative UVR exposure, serum 25-hydroxyvitamin D concentration at immunization, and potential confounding factors. We tested cellular and humoral immune responses in relation to UVR exposure. The delayed-type hypersensitivity response to keyhole limpet hemocyanin recall challenge was lower in individuals with higher personal clothing-adjusted UVR exposure on the day before immunization (P = 0.015) and during intervals spanning the day before to 2-3 days after immunization. There was an incremental increase in T helper type 17 cells (as a proportion of CD4+ T cells) from preimmunization to postimmunization in the high, compared with the low, personal clothing-adjusted UVR exposure group (0.31% vs. -0.39%, P = 0.004). Keyhole limpet hemocyanin-specific antibody titers were not associated with acute or cumulative UVR exposure or serum 25-hydroxyvitamin D levels. Higher UVR exposure at antigen sensitization was associated with a reduced delayed-type hypersensitivity response and altered T helper type 17 kinetics. This has implications for the effectiveness of vaccinations and susceptibility to infections that rely on cell-mediated immune responses.

Personal protective equipment and antiviral drug use during hospitalization for suspected avian or pandemic influenza.

For pandemic influenza planning, realistic estimates of personal protective equipment (PPE) and antiviral medication required for hospital healthcare workers (HCWs) are vital. In this simulation study, a patient with suspected avian or pandemic influenza (API) sought treatment at 9 Australian hospital emergency departments where patient-staff interactions during the first 6 hours of hospitalization were observed. Based on World Health Organization definitions and guidelines, the mean number of "close contacts" of the API patient was 12.3 (range 6-17; 85% HCWs); mean "exposures" were 19.3 (range 15-26). Overall, 20-25 PPE sets were required per patient, with variable HCW compliance for wearing these items (93% N95 masks, 77% gowns, 83% gloves, and 73% eye protection). Up to 41% of HCW close contacts would have qualified for postexposure antiviral prophylaxis. These data indicate that many current national stockpiles of PPE and antiviral medication are likely inadequate for a pandemic.

Validation of Sun Exposure Reported Annually Against Interim Self-report and Daily Sun Diaries.

Data on personal sun exposure over a period exceeding the immediate past days or weeks are typically self-reported in brief questionnaire items. The validity of such self-reporting of longer term personal sun exposure, for example over a year, including detail on variation across seasons, has not previously been investigated. In a volunteer sample (n = 331) of Australian adults aged 18 years and over, we assessed the 12-month reliability of sun exposure reported separately for each season, and its accuracy compared to a daily sun diary in the same season. Seasonal time outdoors displayed fair-to-good reliability between baseline and end of study (12 months), with responses showing higher agreement at lower levels of time outdoors. There was good agreement for ranking of individuals' time outdoors with the daily sun diary data, although the actual diary time outdoors was typically considerably lower than the self-reported questionnaire data. Place of residence, education, being a smoker, day of the week (i.e. working day vs nonworking day) and working mainly outdoors were significant predictors of agreement. While participants overestimated their actual time outdoors, the self-report questionnaire provided a valid ranking of long-term sun exposure against others in the study that was reliable over time.

Measuring sun exposure in epidemiological studies: Matching the method to the research question.

Sun exposure has risks and benefits for health. Testing these associations requires tools for measuring sun exposure that are feasible and relevant to the time-course of the health outcome. Recent sun exposure, e.g. the last week, is best captured by dosimeters and sun diaries. These can also be used for medium-term sun exposure e.g. over several weeks, but incur a high participant burden. Self-reported data on "typical time outdoors" for working and non-working days, is less detailed and not influenced by day-to-day variation. Over a longer period, e.g. the lifetime, or for particular life stages, proxies of sun exposure, such as latitude of residence or ambient ultraviolet (UV) radiation levels (from satellites or ground-level monitoring) can be used, with additional detail provided by lifetime sun exposure calendars that include locations of residence, usual time outdoors, and detail of sunburn episodes. Objective measures of lifetime sun exposure include microtopography of sun-exposed skin (e.g. using silicone casts) or conjunctival UV autofluorescence. Potential modifiers of the association between sun exposure and the health outcome, such as clothing coverage and skin colour, may also need to be measured. We provide a systematic approach to selecting sun exposure measures for use in epidemiological health research.

Tribute to Professor Anthony J. McMichael.

Emeritus Professor A. J. "Tony" McMichael (1942-2014) was an internationally renowned and pioneering Australian academic and advocate in epidemiology, who was passionate about understanding the influences of the environment on human health. In an illustrious career spanning more than four decades, he made significant contributions to the scientific community and policy discourse-including ground-breaking research related to the health of children. McMichael was a prolific academic writer with over 300 peer-reviewed papers; 160 book chapters and two sole-authored books. However, his outstanding talent was for integrating complex and seemingly unrelated strands from the environmental and health sciences into a cohesive narrative-and highlighting its relevance to lay persons, scientists and governments alike. He was instrumental in validating this nascent field of research and inspiring many others to follow his lead.

Will Global Climate Change Alter Fundamental Human Immune Reactivity: Implications for Child Health?

The human immune system is an interface across which many climate change sensitive exposures can affect health outcomes. Gaining an understanding of the range of potential effects that climate change could have on immune function will be of considerable importance, particularly for child health, but has, as yet, received minimal research attention. We postulate several mechanisms whereby climate change sensitive exposures and conditions will subtly impair aspects of the human immune response, thereby altering the distribution of vulnerability within populations-particularly for children-to infection and disease. Key climate change-sensitive pathways include under-nutrition, psychological stress and exposure to ambient ultraviolet radiation, with effects on susceptibility to infection, allergy and autoimmune diseases. Other climate change sensitive exposures may also be important and interact, either additively or synergistically, to alter health risks. Conducting directed research in this area is imperative as the potential public health implications of climate change-induced weakening of the immune system at both individual and population levels are profound. This is particularly relevant for the already vulnerable children of the developing world, who will bear a disproportionate burden of future adverse environmental and geopolitical consequences of climate change.

A 16-year prospective study of community-onset bacteremic Acinetobacter pneumonia: low mortality with appropriate initial empirical antibiotic protocols.

BACKGROUND: The genus Acinetobacter, well known as a nosocomial pathogen, can also cause severe community-onset pneumonia. Previous small case series have suggested fulminant disease and a pooled hospital mortality of > 60%. METHODS: We conducted a prospective observational study of all episodes of bacteremic, community-onset, and radiologically confirmed pneumonia due to Acinetobacter species at a tertiary referral hospital in tropical Australia from 1997 to 2012 following the introduction of routine empirical treatment protocols covering Acinetobacter. Demographic, clinical, microbiologic, and outcome data were collected. RESULTS: There were 41 episodes of bacteremic community-onset Acinetobacter pneumonia, of which 36 had no indicators suggesting health-care-associated infection. Of these, 38 (93%) were Indigenous Australians, one-half were men, the average age was 44.1 years, and 36 episodes (88%) occurred during the rainy season. All patients had at least one risk factor, with hazardous alcohol intake in 82%. Of the 37 isolates available for molecular speciation, 35 were Acinetobacter baumannii and two were Acinetobacter nosocomialis. All isolates were susceptible in vitro to gentamicin, meropenem, and ciprofloxacin, but only one was fully susceptible to ceftriaxone. ICU admission was required in 80%. All 41 patients received appropriate antibiotics within the first 24 h of admission, and 28- and 90-day mortality were both low at 11%. CONCLUSIONS: Community-acquired Acinetobacter pneumonia is a severe disease, with the majority of patients requiring ICU admission. Most patients have risk factors, particularly hazardous alcohol use. Despite this severity, correct initial empirical antibiotic therapy in all patients was associated with low mortality.

Validation of brief questionnaire measures of sun exposure and skin pigmentation against detailed and objective measures including vitamin D status.

Self-reported sun exposure is commonly used in research, but how well this represents actual sun exposure is poorly understood. From February to July 2011, a volunteer sample (n = 47) of older adults (≥45 years) in Canberra, Australia, answered brief questions on time outdoors (weekdays and weekends) and natural skin color. They subsequently maintained a sun diary and wore an ultraviolet radiation (UVR) digital dosimeter for 7 days. Melanin density was estimated using reflectance spectrophotometry; lifetime sun damage was assessed using silicone casts of the back of the hand; and serum 25-hydroxyvitamin D (25(OH)D) concentration was assayed. Questionnaire-reported time outdoors correlated significantly with diary-recorded time outdoors (Spearman correlation r(s) = 0.66; 95% CI 0.46, 0.80; P < 0.001) and UVR dosimeter dose (r(s ) = 0.46; 95% CI 0.18, 0.68; P = 0.003), but not 25(OH)D concentration (r(s) = 0.24; 95% CI -0.05, 0.50; P = 0.10). Questionnaire-reported untanned skin color correlated significantly with measured melanin density at the inner upper arm (r(s) = 0.49; 95% CI 0.24, 0.68; P < 0.001). In a multiple linear regression model, statistically significant predictors of 25(OH)D concentration were self-reported frequency of physical activity, skin color and recent osteoporosis treatment (R(2) = 0.54). In this study, brief questionnaire items provided valid rankings of sun exposure and skin color, and enabled the development of a predictive model for 25(OH)D concentration.

Climate change and infectious diseases in Australia: future prospects, adaptation options, and research priorities.

Climate change will have significant and diverse impacts on human health. These impacts will include changes in infectious disease incidence. In this article, the authors review the current situation and potential future climate change impacts for respiratory, diarrheal, and vector-borne diseases in Australia. Based on this review, the authors suggest adaptive strategies within the health sector and also recommend future research priorities.

A global study of pathogens and host risk factors associated with infectious gastrointestinal disease in returned international travellers.

OBJECTIVES: Infectious gastrointestinal disease (IGD) is a significant cause of morbidity in returned international travellers. This study aims to elucidate host and travel characteristics associated with IGD presentation, and describe the broad spectrum of aetiological pathogens responsible by geographic region of acquisition and reason for travel. METHODS: We analyzed demographic, clinical and microbiological data recorded for ill, returned international travellers presenting to GeoSentinel Surveillance Network sites globally during the period September 1996-December 2005. RESULTS: A total of 25,867 returned travellers were analyzed, of whom 7442 (29%) patients had a total of 8273 IGD diagnoses. Multivariate analysis demonstrated that IGD presentation was associated significantly with female sex (OR: 1.11; p=0.001); younger age group; attending a pre-travel medical appointment (OR: 1.28; p<0.0001); and travelling for the reason of tourism. Travelling for longer periods (>28 days) was associated with lower risk (OR: 0.93; p=0.04). Of the 2902 clinically significant pathogens isolated, 65% were parasitic, 31% bacterial and 3% viral. Presentation of IGD by specific pathogen varied markedly dependent on geographic region of recent travel, and reason for travel. CONCLUSIONS: Host characteristics, region of travel and category of traveller, significantly impact on the relative likelihood of presenting with a broad range of pathogen-specific IGD.

Chikungunya virus infection in travellers to Australia.

We report eight recent cases of Chikungunya virus infection in travellers to Australia. Patients presented with fevers, rigors, headaches, arthralgia, and rash. The current Indian Ocean epidemic and Italian outbreak have featured prominently on Internet infectious disease bulletins, and Chikungunya virus infection had been anticipated in travellers from the outbreak areas. Diagnosis was by a generic alphavirus reverse transcriptase polymerase chain reaction with confirmatory sequencing. Prompt diagnosis of Chikungunya virus infections is of public health significance as the mosquito vectors for transmission exist in Australia. There is potential for this infection to spread in the largely naïve Australian population.

Adaptation of the NegEx algorithm to Veterans Affairs electronic text notes for detection of influenza-like illness (ILI).

We tested automated detection of influenza-like illness (ILI) from free-text clinician notes extracted from the VA electronic medical record using a simple negation algorithm coupled with string matching for relevant ILI symptoms mapped to UMLS concepts. Additionally, we documented negation problems encountered and adaptations made to the negation algorithm when applied to the full texts of a diverse array of VA note types and templates.