A Niche for Infectious Disease in Environmental Health: Rethinking the Toxicological Paradigm

Objective

In this review we highlight the need to expand the scope of environmental health research, which now focuses largely on the study of toxicants, to incorporate infectious agents. We provide evidence that environmental health research would be strengthened through finding common ground with the tools and approaches of infectious disease research.

Data sources and extraction

We conducted a literature review for examples of interactions between toxic agents and infectious diseases, as well as the role of these interactions as risk factors in classic “environmental” diseases. We investigated existing funding sources and research mandates in the United States from the National Science Foundation and the National Institutes of Health, particularly the National Institute of Environmental Health Sciences.

Data synthesis

We adapted the toxicological paradigm to guide reintegration of infectious disease into environmental health research and to identify common ground between these two fields as well as opportunities for improving public health through interdisciplinary research.

Conclusions

Environmental health encompasses complex disease processes, many of which involve interactions among multiple risk factors, including toxicant exposures, pathogens, and susceptibility. Funding and program mandates for environmental health studies should be expanded to include pathogens in order to capture the true scope of these overlapping risks, thus creating more effective research investments with greater relevance to the complexity of real-world exposures and multifactorial health outcomes. We propose a new model that integrates the toxicology and infectious disease paradigms to facilitate improved collaboration and communication by providing a framework for interdisciplinary research. Pathogens should be part of environmental health research planning and funding allocation, as well as applications such as surveillance and policy development.     

Environmental Exposure,Obesity, and Parkinson’s Disease: Lessons from Fat and Old Worms

Background

A common link has been exposed, namely, that metal exposure plays a role in obesity and in Parkinson’s disease (PD). This link may help to elucidate mechanisms of neurotoxicity.

Objective

We reviewed the utility of the nematode, Caenorhabditis elegans, as a model organism to study neurodegeneration in obesity and Parkinson’s disease (PD), with an emphasis on the neurotransmitter, dopamine (DA).

Data sources

A PubMed literature search was performed using the terms “obesity” and any of the following: “C. elegans,” “central nervous system,” “neurodegeneration,” “heavy metals,” “dopamine” or “Parkinson’s disease.” We reviewed the identified studies, including others cited therein, to summarize the current evidence of neurodegeneration in obesity and PD, with an emphasis on studies carried out in C. elegans and environmental toxins in the etiology of both diseases.

Data extraction and data synthesis

Heavy metals and DA have both been linked to diet-induced obesity, which has led to the notion that the mechanism of environmentally induced neurodegeneration in PD may also apply to obesity. C. elegans has been instrumental in expanding our mechanism-based knowledge of PD, and this species is emerging as a good model of obesity. With well-established toxicity and neurogenetic assays, it is now feasible to explore the putative link between metal-and chemical-induced neurodegeneration.

Conclusions

One side effect of an aging population is an increase in the prevalence of obesity, metabolic disorders, and neurodegenerative orders, diseases that are likely to co-occur. Environmental toxins, especially heavy metals, may prove to be a previously neglected part of the puzzle.     

Low-Dose Arsenic Compromises the Immune Response to Influenza A Infection in Vivo

Background

Arsenic exposure is a significant worldwide environmental health concern. We recently reported that 5-week exposure to environmentally relevant levels (10 and 100 ppb) of As in drinking water significantly altered components of the innate immune response in mouse lung, which we hypothesize is an important contributor to the increased risk of lung disease in exposed human populations.

Objectives

We investigated the effects of As exposure on respiratory influenza A (H1N1) virus infection, a common and potentially fatal disease.

Methods

In this study, we exposed C57BL/6J mice to 100 ppb As in drinking water for 5 weeks, followed by intranasal inoculation with a sub lethal dose of influenza A/PuertoRico/8/34 (H1N1) virus. Multiple end points were assessed postinfection.

Results

Arsenic was associated with a number of significant changes in response to influenza, including an increase in morbidity and higher pulmonary influenza virus titers on day 7 post-infection. We also found many alterations in the immune response relative to As-unexposed controls, including a decrease in the number of dendritic cells in the mediastinal lymph nodes early in the course of infection.

Conclusions

Our data indicate that chronic As exposure significantly compromises the immune response to infection. Alterations in response to repeated lung infection may also contribute to other chronic illnesses, such as bronchiectasis, which is elevated by As exposure in epidemiology studies.     

Meeting Report: Moving Upstream—Evaluating Adverse Upstream End Points for Improved Risk Assessment and Decision-Making

Background

Assessing adverse effects from environmental chemical exposure is integral to public health policies. Toxicology assays identifying early biological changes from chemical exposure are increasing our ability to evaluate links between early biological disturbances and subsequent overt downstream effects. A workshop was held to consider how the resulting data inform consideration of an “adverse effect” in the context of hazard identification and risk assessment.

Objectives

Our objective here is to review what is known about the relationships between chemical exposure, early biological effects (upstream events), and later overt effects (downstream events) through three case studies (thyroid hormone disruption, antiandrogen effects, immune system disruption) and to consider how to evaluate hazard and risk when early biological effect data are available.

Discussion

Each case study presents data on the toxicity pathways linking early biological perturbations with downstream overt effects. Case studies also emphasize several factors that can influence risk of overt disease as a result from early biological perturbations, including background chemical exposures, underlying individual biological processes, and disease susceptibility. Certain effects resulting from exposure during periods of sensitivity may be irreversible. A chemical can act through multiple modes of action, resulting in similar or different overt effects.

Conclusions

For certain classes of early perturbations, sufficient information on the disease process is known, so hazard and quantitative risk assessment can proceed using information on upstream biological perturbations. Upstream data will support improved approaches for considering developmental stage, background exposures, disease status, and other factors important to assessing hazard and risk for the whole population.     

Sustainable Control of Water-Related Infectious Diseases: A Review and Proposal for Interdisciplinary Health-Based Systems Research

Objective

Even when initially successful, many interventions aimed at reducing the toll of water-related infectious disease have not been sustainable over longer periods of time. Here we review historical practices in water-related infectious disease research and propose an interdisciplinary public health oriented systems approach to research and intervention design.

Data sources

On the basis of the literature and the authors’ experiences, we summarize contributions from key disciplines and identify common problems and trends. Practices in developing countries, where the disease burden is the most severe, are emphasized.

Data extraction

We define waterborne and water-associated vectorborne diseases and identify disciplinary themes and conceptual needs by drawing from ecologic, anthropologic, engineering, political/economic, and public health fields. A case study examines one of the classes of water-related infectious disease.

Data synthesis

The limited success in designing sustainable interventions is attributable to factors that include the complexity and interactions among the social, ecologic, engineering, political/economic, and public health domains; incomplete data; a lack of relevant indicators; and most important, an inadequate understanding of the proximal and distal factors that cause water-related infectious disease. Fundamental change is needed for research on water-related infectious diseases, and we advocate a systems approach framework using an ongoing evidence-based health outcomes focus with an extended time horizon. The examples and case study in the review show many opportunities for interdisciplinary collaborations, data fusion techniques, and other advances.

Conclusions

The proposed framework will facilitate research by addressing the complexity and divergent scales of problems and by engaging scientists in the disciplines needed to tackle these difficult problems. Such research can enhance the prevention and control of water-related infectious diseases in a manner that is sustainable and focused on public health outcomes.     

Do TETRA (Airwave) Base Station Signals Have a Short-Term Impact on Health and Well-Being? A Randomized Double-Blind Provocation Study

Background

“Airwave” is the new communication system currently being rolled out across the United Kingdom for the police and emergency services, based on the Terrestrial Trunked Radio Telecommunications System (TETRA). Some police officers have complained about skin rashes, nausea, headaches, and depression as a consequence of using their Airwave handsets. In addition, a small subgroup in the population self-report being sensitive to electromagnetic fields (EMFs) in general.

Objectives

We conducted a randomized double-blind provocation study to establish whether short-term exposure to a TETRA base station signal has an impact on the health and well-being of individuals with self-reported “electrosensitivity” and of participants who served as controls.

Methods

Fifty-one individuals with self-reported electrosensitivity and 132 age- and sex-matched controls participated in an open provocation test; 48 sensitive and 132 control participants went on to complete double-blind tests in a fully screened semianechoic chamber. Heart rate, skin conductance, and blood pressure readings provided objective indices of short-term physiological response. Visual analog scales and symptom scales provided subjective indices of well-being.

Results

We found no differences on any measure between TETRA and sham (no signal) under double-blind conditions for either controls or electrosensitive participants, and neither group could detect the presence of a TETRA signal at rates greater than chance (50%). When conditions were not double blind, however, the self-reported electrosensitive individuals did report feeling worse and experienced more severe symptoms during TETRA compared with sham.

Conclusions

Our findings suggest that the adverse symptoms experienced by electrosensitive individuals are due to the belief of harm from TETRA base stations rather than to the low-level EMF exposure itself.     

Thyroid-Disrupting Chemicals: Interpreting Upstream Biomarkers of Adverse Outcomes

Background

There is increasing evidence in humans and in experimental animals for a relationship between exposure to specific environmental chemicals and perturbations in levels of critically important thyroid hormones (THs). Identification and proper interpretation of these relationships are required for accurate assessment of risk to public health.

Objectives

We review the role of TH in nervous system development and specific outcomes in adults, the impact of xenobiotics on thyroid signaling, the relationship between adverse outcomes of thyroid disruption and upstream causal biomarkers, and the societal implications of perturbations in thyroid signaling by xenobiotic chemicals.

Data sources

We drew on an extensive body of epidemiologic, toxicologic, and mechanistic studies.

Data synthesis

THs are critical for normal nervous system development, and decreased maternal TH levels are associated with adverse neuropsychological development in children. In adult humans, increased thyroid-stimulating hormone is associated with increased blood pressure and poorer blood lipid profiles, both risk factors for cardiovascular disease and death. These effects of thyroid suppression are observed even within the “normal” range for the population. Environmental chemicals may affect thyroid homeostasis by a number of mechanisms, and multiple chemicals have been identified that interfere with thyroid function by each of the identified mechanisms.

Conclusions

Individuals are potentially vulnerable to adverse effects as a consequence of exposure to thyroid-disrupting chemicals. Any degree of thyroid disruption that affects TH levels on a population basis should be considered a biomarker of adverse outcomes, which may have important societal outcomes.     

From Good Intentions to Proven Interventions: Effectiveness of Actions to Reduce the Health Impacts of Air Pollution

Background

Associations between air pollution and a multitude of health effects are now well established. Given ubiquitous exposure to some level of air pollution, the attributable health burden can be high, particularly for susceptible populations.

Objectives

An international multidisciplinary workshop was convened to discuss evidence of the effectiveness of actions to reduce health impacts of air pollution at both the community and individual level. The overall aim was to summarize current knowledge regarding air pollution exposure and health impacts leading to public health recommendations.

Discussion

During the workshop, experts reviewed the biological mechanisms of action of air pollution in the initiation and progression of disease, as well as the state of the science regarding community and individual-level interventions. The workshop highlighted strategies to reduce individual baseline risk of conditions associated with increased susceptibility to the effects of air pollution and the need to better understand the role of exposure duration in disease progression, reversal, and adaptation.

Conclusion

We have identified two promising and largely unexplored strategies to address and mitigate air pollution–related health impacts: reducing individual baseline risk of cardiovascular disease and incorporating air pollution–related health impacts into land-use decisions.     

Biological Monitoring for Depleted Uranium Exposure in U.S. Veterans

Background

As part of an ongoing medical surveillance program for U.S. veterans exposed to depleted uranium (DU), biological monitoring of urine uranium (U) concentrations is offered to any veteran of the Gulf War and those serving in more recent conflicts (post-Gulf War veterans).

Objectives

Since a previous report of surveillance findings in 2004, an improved methodology for determination of the isotopic ratio of U in urine (²³⁵U:²³⁸U) has been developed and allows for more definitive evaluation of DU exposure. This report updates previous findings.

Methods

Veterans provide a 24-hr urine specimen and complete a DU exposure questionnaire. Specimens are sent to the Baltimore Veterans Affairs Medical Center for processing. Uranium concentration and isotopic ratio are measured using ICP-MS at the Armed Forces Institute of Pathology.

Results

Between January 2003 and June 2008, we received 1,769 urine specimens for U analysis. The mean urine U measure was 0.009 μg U/g creatinine. Mean urine U concentrations for Gulf War and post-Gulf War veterans were 0.008 and 0.009 μg U/g creatinine, respectively. Only 3 of the 1,700 (0.01%) specimens for which we completed isotopic determination showed evidence of DU. Exposure histories confirmed that these three individuals had been involved in “friendly fire” incidents involving DU munitions or armored vehicles.

Conclusions

No urine U measure with a “depleted” isotopic signature has been detected in U.S. veterans without a history of retained DU embedded fragments from previous injury. These findings suggest that future DU-related health harm is unlikely in veterans without DU fragments.     

Global Association of Cold Spells and Adverse Health Effects: A Systematic Review and Meta-Analysis

Background

There is substantial evidence that mortality increases in low temperatures. Less is known about the role of prolonged cold periods denoted as cold spells.

Objective

We conducted the first systematic review and meta-analysis to summarize the evidence on the adverse health effects of cold spells in varying climates.

Data sources and extraction

Four databases (Ovid Medline, PubMed, Scopus, Web of Science) were searched for all years and languages available. “Cold spell” was defined as an event below a temperature threshold lasting for a minimum duration of 2 days. Of 1,527 identified articles, 26 satisfied our eligibility criteria for the systematic review, and 9 were eligible for meta-analyses. The articles were grouped by the three main study questions into Overall-effect Group, Added-effect Group, and Temperature-change-effect Group.

Data synthesis

Based on random-effects models in the meta-analyses, cold spells were associated with increased mortality from all or all nonaccidental causes (summary rate ratio = 1.10; 95% CI: 1.04, 1.17 based on 9 estimates from five studies), cardiovascular diseases (1.11; 95% CI: 1.03, 1.19; 12 estimates from eight studies), and respiratory diseases (1.21; 95% CI: 0.97, 1.51; 8 estimates from four studies). Estimated associations were stronger for people ≥ 65 years of age (1.06; 95% CI: 1.00, 1.12) than for people 0–64 years of age (1.01; 95% CI: 1.00, 1.03). Study-specific effect estimates from a limited number of studies suggested an increased morbidity related to cold spells, but it was not possible to quantitatively summarize the evidence.

Conclusions

Cold spells are associated with increased mortality rates in populations around the world. The body of evidence suggests that cold spells also have other adverse health effects. There was substantial heterogeneity among the studies, which should be taken into account in the interpretation of the results.

Citation

Ryti NR, Guo Y, Jaakkola JJ. 2016. Global association of cold spells and adverse health effects: a systematic review and meta-analysis. Environ Health Perspect 124:12–22; http://dx.doi.org/10.1289/ehp.1408104     

A Clash of Old and New Scientific Concepts in Toxicity,with Important Implications for Public Health

Background

A core assumption of current toxicologic procedures used to establish health standards for chemical exposures is that testing the safety of chemicals at high doses can be used to predict the effects of low-dose exposures, such as those common in the general population. This assumption is based on the precept that “the dose makes the poison”: higher doses will cause greater effects.

Objectives

We challenge the validity of assuming that high-dose testing can be used to predict low-dose effects for contaminants that behave like hormones. We review data from endocrinology and toxicology that falsify this assumption and summarize current mechanistic understanding of how low doses can lead to effects unpredictable from high-dose experiments.

Discussion

Falsification of this assumption raises profound issues for regulatory toxicology. Many exposure standards are based on this assumption. Rejecting the assumption will require that these standards be reevaluated and that procedures employed to set health standards be changed. The consequences of these changes may be significant for public health because of the range of health conditions now plausibly linked to exposure to endocrine-disrupting contaminants.

Conclusions

We recommend that procedures to establish acceptable exposure levels for endocrine-disrupting compounds incorporate the inability for high-dose tests to predict low-dose results. Setting acceptable levels of exposure must include testing for health consequences at prevalent levels of human exposure, not extrapolations from the effects observed in high-dose experiments. Scientists trained in endocrinology must be engaged systematically in standard setting for endocrine-disrupting compounds.     

Perturbation of Defense Pathways by Low-Dose Arsenic Exposure in Zebrafish Embryos

Background

Exposure to arsenic is a critical risk factor in the complex interplay among genetics, the environment, and human disease. Despite the potential for in utero exposure, the mechanism of arsenic action on vertebrate development and disease is unknown.

Objectives

The objective of this study was to identify genes and gene networks perturbed by arsenic during development in order to enhance understanding of the molecular mechanisms of arsenic action.

Methods

We exposed zebrafish embryos at 0.25–1.25 hr postfertilization to 10 or 100 ppb arsenic for 24 or 48 hr. We then used total RNA to interrogate genome microarrays and to test levels of gene expression changes by quantitative real-time polymerase chain reaction (QPCR). Computational analysis was used to identify gene expression networks perturbed by arsenic during vertebrate development.

Results

We identified a set of 99 genes that responded to low levels of arsenic. Nineteen of these genes were predicted to function in a common regulatory network that was significantly associated with immune response and cancer (p < 10⁻⁴¹). Arsenic-mediated expression changes were validated by QPCR.

Conclusions

In this study we demonstrated that arsenic significantly down-regulates expression levels of multiple genes potentially critical for regulating the establishment of an immune response. The data also provide molecular evidence consistent with phenotypic observations reported in other model systems. Additional mechanistic studies will help explain molecular events regulating early stages of the immune system and long-term consequences of arsenic-mediated perturbation of this system during development.     

Computational Toxicology: Realizing the Promise of the Toxicity Testing in the 21st Century

Background

The National Academies’ Standing Committee on Use of Emerging Science for Environmental Health Decisions held a meeting (21–22 September 2009 in Washington, DC) titled “Computational Toxicology: From Data to Analyses to Applications.” This commentary reflects on the presentations and roundtable discussions from the meeting that were designed to review the state of the art in the field and the practical applications of the new science and to provide focus to the field.

Objectives

The meeting considered two topics: the emerging data streams amenable to computational modeling and data mining, and the emerging data analysis and modeling tools.

Discussion

Computational toxicology is a subdiscipline of toxicology that aims to use the mathematical, statistical, modeling, and computer science tools to better understand the mechanisms through which a given chemical induces harm and, ultimately, to be able to predict adverse effects of the toxicants on human health and/or the environment. The participants stressed the importance of computational toxicology to the future of environmental health sciences and regulatory decisions in public health; however, many challenges remain to be addressed before the findings from high-throughput screens and in silico models may be considered sufficiently robust and informative.

Conclusions

Many scientists, regulators, and the general public believe that new and better ways to assess human toxicity are now needed, and technological breakthroughs are empowering the field of toxicity assessment. Even though the application of computational toxicology to environmental health decisions requires additional efforts, the merger of the power of computers with biological information is poised to deliver new tools and knowledge.     

Disruption of MicroRNA Expression in Human Airway Cells by Diesel Exhaust Particles Is Linked to Tumorigenesis-Associated Pathways

Background

Particulate matter (PM) is associated with adverse airway health effects; however, the underlying mechanism in disease initiation is still largely unknown. Recently, microRNAs (miRNAs; small noncoding RNAs) have been suggested to be important in maintaining the lung in a disease-free state through regulation of gene expression. Although many studies have shown aberrant miRNA expression patterns in diseased versus healthy tissue, little is known regarding whether environmental agents can induce such changes.

Objectives

We used diesel exhaust particles (DEP), the largest source of emitted airborne PM, to investigate pollutant-induced changes in miRNA expression in airway epithelial cells. We hypothesized that DEP exposure can lead to disruption of normal miRNA expression patterns, representing a plausible novel mechanism through which DEP can mediate disease initiation.

Methods

Human bronchial epithelial cells were grown at air–liquid interface until they reached mucociliary differentiation. After treating the cells with 10 μg/cm² DEP for 24 hr, we analyzed total RNA for miRNA expression using microarray profile analysis and quantitative real-time polymerase chain reaction.

Results

DEP exposure changed the miRNA expression profile in human airway epithelial cells. Specifically, 197 of 313 detectable miRNAs (62.9%) were either up-regulated or down-regulated by 1.5-fold. Molecular network analysis of putative targets of the 12 most altered miRNAs indicated that DEP exposure is associated with inflammatory responses pathways and a strong tumorigenic disease signature.

Conclusions

Alteration of miRNA expression profiles by environmental pollutants such as DEP can modify cellular processes by regulation of gene expression, which may lead to disease pathogenesis.     

Human Neurospheres as Three-Dimensional Cellular Systems for Developmental Neurotoxicity Testing

Background

Developmental neurotoxicity (DNT) of environmental chemicals is a serious threat to human health. Current DNT testing guidelines propose investigations in rodents, which require large numbers of animals. With regard to the “3 Rs” (reduction, replacement, and refinement) of animal testing and the European regulation of chemicals [Registration, Evaluation, and Authorisation of Chemicals (REACH)], alternative testing strategies are needed in order to refine and reduce animal experiments and allow faster and less expensive screening.

Objectives

The goal of this study was to establish a three-dimensional test system for DNT screening based on human fetal brain cells.

Methods

We established assays suitable for detecting disturbances in basic processes of brain development by employing human neural progenitor cells (hNPCs), which grow as neurospheres. Furthermore, we assessed effects of mercury and oxidative stress on these cells.

Results

We found that human neurospheres imitate proliferation, differentiation, and migration in vitro. Exposure to the proapoptotic agent staurosporine further suggests that human neurospheres possess functioning apoptosis machinery. The developmental neurotoxicants methylmercury chloride and mercury chloride decreased migration distance and number of neuronal-like cells in differentiated hNPCs. Furthermore, hNPCs undergo caspase-independent apoptosis when exposed toward high amounts of oxidative stress.

Conclusions

Human neurospheres are likely to imitate basic processes of brain development, and these processes can be modulated by developmental neurotoxicants. Thus, this three-dimensional cell system is a promising approach for DNT testing.     

U.S. Funding Is Insufficient to Address the Human Health Impacts of and Public Health Responses to Climate Variability and Change

Background

The need to identify and try to prevent adverse health impacts of climate change has risen to the forefront of climate change policy debates and become a top priority of the public health community. Given the observed and projected changes in climate and weather patterns, their current and anticipated health impacts, and the significant degree of regulatory discussion underway in the U.S. government, it is reasonable to determine the extent of federal investment in research to understand, avoid, prepare for, and respond to the human health impacts of climate change in the United States.

Objective

In this commentary we summarize the health risks of climate change in the United States and examine the extent of federal funding devoted to understanding, avoiding, preparing for, and responding to the human health risks of climate change.

Discussion

Future climate change is projected to exacerbate various current health problems, including heat-related mortality, diarrheal diseases, and diseases associated with exposure to ozone and aeroallergens. Demographic trends and geophysical and socioeconomic factors could increase overall vulnerability. Despite these risks, extramural federal funding of climate change and health research is estimated to be < $3 million per year.

Conclusions

Given the real risks that climate change poses for U.S. populations, the National Institutes of Health, Centers for Disease Control and Prevention, U.S. Environmental Protection Agency, and other agencies need to have robust intramural and extramural programs, with funding of > $200 million annually. Oversight of the size and priorities of these programs could be provided by a standing committee within the National Academy of Sciences.     

The 2006 California Heat Wave: Impacts on Hospitalizations and Emergency Department Visits

Background

Climate models project that heat waves will increase in frequency and severity. Despite many studies of mortality from heat waves, few studies have examined morbidity.

Objectives

In this study we investigated whether any age or race/ethnicity groups experienced increased hospitalizations and emergency department (ED) visits overall or for selected illnesses during the 2006 California heat wave.

Methods

We aggregated county-level hospitalizations and ED visits for all causes and for 10 cause groups into six geographic regions of California. We calculated excess morbidity and rate ratios (RRs) during the heat wave (15 July to 1 August 2006) and compared these data with those of a reference period (8–14 July and 12–22 August 2006).

Results

During the heat wave, 16,166 excess ED visits and 1,182 excess hospitalizations occurred statewide. ED visits for heat-related causes increased across the state [RR = 6.30; 95% confidence interval (CI), 5.67–7.01], especially in the Central Coast region, which includes San Francisco. Children (0–4 years of age) and the elderly (≥ 65 years of age) were at greatest risk. ED visits also showed significant increases for acute renal failure, cardiovascular diseases, diabetes, electrolyte imbalance, and nephritis. We observed significantly elevated RRs for hospitalizations for heat-related illnesses (RR = 10.15; 95% CI, 7.79–13.43), acute renal failure, electrolyte imbalance, and nephritis.

Conclusions

The 2006 California heat wave had a substantial effect on morbidity, including regions with relatively modest temperatures. This suggests that population acclimatization and adaptive capacity influenced risk. By better understanding these impacts and population vulnerabilities, local communities can improve heat wave preparedness to cope with a globally warming future.     

Global climate change and children's health: threats and strategies for prevention

Background

Global climate change will have multiple effects on human health. Vulnerable populations—children, the elderly, and the poor—will be disproportionately affected.

Objective

We reviewed projected impacts of climate change on children’s health, the pathways involved in these effects, and prevention strategies.

Data sources

We assessed primary studies, review articles, and organizational reports.

Data synthesis

Climate change is increasing the global burden of disease and in the year 2000 was responsible for > 150,000 deaths worldwide. Of this disease burden, 88% fell upon children. Documented health effects include changing ranges of vector-borne diseases such as malaria and dengue; increased diarrheal and respiratory disease; increased morbidity and mortality from extreme weather; changed exposures to toxic chemicals; worsened poverty; food and physical insecurity; and threats to human habitation. Heat-related health effects for which research is emerging include diminished school performance, increased rates of pregnancy complications, and renal effects. Stark variation in these outcomes is evident by geographic region and socioeconomic status, and these impacts will exacerbate health disparities. Prevention strategies to reduce health impacts of climate change include reduction of greenhouse gas emissions and adaptation through multiple public health interventions.

Conclusions

Further quantification of the effects of climate change on children’s health is needed globally and also at regional and local levels through enhanced monitoring of children’s environmental health and by tracking selected indicators. Climate change preparedness strategies need to be incorporated into public health programs.