Developmental Neurotoxicity of Domoic Acid: Evidence for a Critical Window of Exposure

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Harmful algal blooms are a growing worldwide problem.1 Toxins produced by some of these algae, including the neurotoxin domoic acid (DomA), may reach humans through contaminated seafood consumption.2^,3 Because acute high-level exposure may cause amnesic shellfish poisoning,4 countries around the world limit DomA to 20μg/g of shellfish tissue.5^,6^,7 However, relatively little is known about the health effects of chronic low-level exposure such as that experienced by people who regularly eat shellfish.8^,9^,10 In a recent study11 in Environmental Health Perspectives investigators based at the Woods Hole Oceanographic Institution (WHOI) in Massachusetts analyzed the developmental neurotoxic effects of DomA in zebrafish to help fill this gap.Open in a separate windowDomoic acid is produced by algal species including members of the Pseudo-nitzschia genus (shown). It causes amnesic shellfish poisoning, a potentially fatal illness that can strike people who eat contaminated seafood, such as clams, mussels, and crab. The disease was only discovered in 1987.3 Image: Pseudo-nitzschia: Vera Trainer/NOAA; razor clams: © iStockphoto/jack looney.The researchers exposed zebrafish embryos and larvae to DomA doses that were 3- to 260-fold lower than exposures tested in earlier studies.12^,13 Even the lowest nominal dose of 0.09ng during a defined developmental window caused behavioral deficits in the larvae. The researchers causally linked these deficits to disrupted myelination processes and altered gene expression.Zebrafish have distinct advantages as a model organism. Embryos are transparent during early development, and their nervous system structures are similar to those of humans. However, in zebrafish these structures develop externally rather than hidden inside a uterus. Thus, real-time imaging can reveal changes in labeled cells of interest during very early stages of development.Instead of the usual method of adding the agent of interest to the fish tanks, the researchers used microinjection into a cardinal vein to deliver a single dose of 0.09–0.18ng of DomA to the embryos and larvae. They administered doses at specific developmental periods between 1 and 4 days postfertilization (dpf). “Microinjection ensured that the desired dose reached the embryo and let us precisely time exposures throughout development to home in on a critical window,” says first author Jennifer M. Panlilio, who performed the research as a doctoral student in a joint program between WHOI and Massachusetts Institute of Technology.Following the injection, fluorescence time-lapse microscopy was used to track the movement of specialized cells in the spinal cord and the formation of protective myelin sheaths around axons, the part of the neuron that transmits electrical signals. Larval RNA was sequenced at 3 and 7 dpf, and myelin structure was assessed at 5–7 dpf. At 7 dpf, the researchers measured the larvae’s startle behavior in response to acoustic/vibrational stimuli. Well-known neural circuits and cell types drive this behavior.14^,15Exposure to 0.09ng DomA at 2 dpf had effects that were not observed at 1 or 4 dpf. It reduced the expression of genes required for maintaining axon and myelin structure, it produced structural deficits in myelin sheaths, and it delayed and changed typical motion features of the larvae’s startle response. However, it had no appreciable effects on mortality or gross morphology.“Our novel finding is a narrow critical window of development when DomA exposure disrupts the initial myelination of axons,” says Panlilio. “This is a potential molecular basis for an observable behavior, which provides an important functional end point for future research.” Even if the end point is similar in other organisms, she adds, the critical window may be different. The myelination process in humans, for example, starts in utero and continues throughout adolescence.For Rebekah Petroff, who was not involved in the new study, the results are consistent with observations in rodents,16^,17^,18^,19 marine mammals,20^,21 and nonhuman primates.22^,23 Petroff, a postdoctoral fellow at the University of Michigan, has studied DomA neurotoxicity in adult crab-eating macaques after low-level exposure.“Disrupted myelination pathways are a plausible mechanism for developmental end points that have been observed consistently across species,” says Petroff. “However, it will be difficult to translate how important these effects are until we know more about human exposure levels.” For example, the DomA exposure of fetuses and infants whose mothers consume contaminated shellfish is currently unknown.Jennifer Freeman, an associate professor of toxicology at Purdue University, appreciates the study’s precise targeting of different developmental stages. “I think we need to do more of that in developmental toxicology,” says Freeman, who also was not involved in the project. “If you don’t capture the susceptible period, you may completely miss an adverse health outcome.”Freeman finds the alignment of multiple pieces of evidence for the critical window of 2 dpf—namely, structural imaging, gene expression analysis, and functional outcome—compelling and considers it critical for regulating other environmental chemicals.Although researchers have identified several algal genes that produce DomA,24 we have only a limited understanding of the environmental stressors that trigger production of the toxin.25 Rising sea surface temperatures are predicted to increase the frequency of harmful algal blooms, including those with DomA-producing Pseudo-nitzschia species.26 DomA may persist in shellfish tissue long after the blooms dissipate, although substantial between- and within-species variation complicates predictions.27 “It’s a complex problem that’s challenging but important to regulate,” concludes Petroff.     

BPS and Cell Fusion in the Human Placenta: A Separate Mechanism of Action?

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During the past decade, the plasticizer bisphenol S (BPS) has been replacing the endocrine-disrupting chemical bisphenol A (BPA) in numerous consumer products.1^,2 As an example of its prevalence, a survey conducted in the United States and seven Asian countries found BPS in 81% of human urine samples collected.3 Despite the two chemicals’ general similarity, some of their biochemical properties differ.4^,5^,6 This raises the possibility that BPS may affect endocrine organs—including the human placenta—differently than BPA does. Researchers led by Almudena Veiga-Lopez, a visiting associate professor in the Department of Pathology at the University of Illinois at Chicago, explored one such mechanism in a recent in vitro study published in Environmental Health Perspectives.7Open in a separate windowBPS is used in thermal receipt paper and linings of food and beverage cans. It has been found in canned foods, indoor dust, sewage sludge, groundwater, and river sediment. Image: © Robert Hoetink/Shutterstock.Veiga-Lopez and colleagues studied cell fusion processes human placentas collected at the end of healthy pregnancies. The results of their analyses suggest that BPS may interfere with the formation of the syncytiotrophoblast (STB), a layer of epithelial cells in the placenta. The STB prevents the rejection of fetal cells by the maternal immune system, enables the exchange of nutrients and gases between mother and fetus, protects the fetus from some (although not all) harmful chemicals in maternal blood, and secretes its own hormones, such as hCG and progesterone.8The STB is composed of trophoblasts, which are the first cells to differentiate after an egg is fertilized. The authors proposed that BPS interferes with the fusion of trophoblasts into the STB by competing with the epidermal growth factor (EGF) for binding to the EGF receptor (EGFR). EGF is a protein that stimulates cell growth and differentiation throughout the body.9 The researchers analyzed trophoblasts from six term placentas and found that 200ng/mL of BPS blocked EGF-mediated cell fusion in vitro by binding to EGFR. That concentration is at the upper end of the reported urinary range for the U.S. general population.10Importantly, spontaneous cell fusion was not blocked by this dose, suggesting alternative mechanisms may be involved in the interference with STB formation. “Even if BPS were to block all of the cell fusion events that are induced by EGF, cells that were to fuse spontaneously—not through EGF—could still do so,” Veiga-Lopez explains.Although human trophoblasts from term placentas still fuse in vitro, they no longer divide.11^,12 So the researchers also analyzed proliferating breast cancer cells, which are an established model for testing the EGFR-binding activity of environmental chemicals. The results provided additional evidence that BPS acts as an EGFR antagonist.The study raises the possibility that BPS may adversely affect fetal development or increase the risk of pregnancy complications. However, those possibilities hinge on the role of EGF in the cell fusion process in vivo.“The placenta has one of the body’s highest EGFR expression levels, and EGF is among the dominant factors regulating the proliferation, uterine [attachment], and fusion of human trophoblasts,” says Veiga-Lopez. “But other factors are involved as well. Our understanding of these processes is limited, as they are very difficult to study.”EGF likely plays a variety of roles throughout pregnancy.13^,14^,15 In the first trimester, EGF helps the developing placenta attach to the uterus. To nourish the rapidly growing fetus in later pregnancy stages, EGF and other factors primarily control the cell fusion process to keep up with the increasing complexity the villi—the finger-like structures that maximize the embryo’s contact with maternal blood.Any role of BPS in that fusion process is currently uncertain, says R. Michael Roberts, a professor emeritus of reproductive biology at the University of Missouri, who was not involved in the study. “The researchers proposed a new mechanism of action for BPS that is different from alterations of the classical steroid receptor pathway,” he says. “Although intriguing, I think it remains a hypothesis until confirmed by other studies at environmentally relevant doses.”Graham Burton, a professor emeritus of reproductive physiology at the University of Cambridge, United Kingdom, who also was not involved in the study, agrees with the authors’ conclusion that BPS blocks EGF-mediated cell fusion in vitro. However, extrapolating that finding to human pregnancies is difficult, he notes.“BPS may affect trophoblast proliferation early in the course of placental development, but I think it is less likely to affect in vivo syncytialization, as spontaneous fusion was not blocked in their experiments,” says Burton. “At the end of the day, we just don’t know enough about the role of EGF in regulating this complex process.”Recently generated organoid trophoblast cultures16^,17 form structures similar to villi, differentiate into the STB and other cell types, and secrete placenta-specific peptides and hormones. These cultures closely resemble first-trimester placentas and may help clarify the regulation of cell fusion, says Burton.     

Potential Mechanisms behind Air Pollution Toxicity: Findings from Real-World Chronic Exposures

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Traffic is one of the major contributors to air pollution in urban areas; the dynamic mixture of gases and particles that results from vehicle exhaust and noncombustion emissions such as road and tire wear is known as traffic-related air pollution (TRAP).1 The impact of TRAP exposure on human health has been the subject of epidemiological studies for two decades, but the mechanisms by which TRAP-associated particulate matter (PM) alters heart and lung function remain to be elucidated. In a recent pilot study reported in Environmental Health Perspectives, investigators sought to address this issue using a real-world model of TRAP exposure in rats.2Worldwide, ambient air pollution is estimated to cause 3.8 million premature deaths per year due to cardiovascular and respiratory diseases.3^,4 Several studies have reported an association between acute exposure to highly concentrated PM and development of cardiopulmonary dysfunction in humans and animals.5^,6^,7^,8^,9Open in a separate windowThe confined air found in highway tunnels contains levels of TRAP comparable to daily exposures for people who commute or live near busy roads. Image: © ddisq/Shutterstock.Tunnel traffic has been used before to characterize single or well-defined mixtures of TRAP pollutants as well as associated health effects in humans and animals.5^,6^,7^,8^,10 The new study, in contrast, examined health effects of chronic exposure to environmentally relevant doses of real-world TRAP. The animals’ average exposures to fine PM roughly approximated the primary National Ambient Air Quality Standard of 12 μg/m3 per day per year set by the U.S. Environmental Protection Agency (EPA).11David Diaz-Sanchez, director of the Public Health and Integrated Toxicology Division at the EPA Center for Public Health and Environmental Assessment, says the inclusion of both males and females is another unique feature of this study. “Some epidemiological studies have looked at [sex-dependent differences on TRAP exposure effects], but their results are often confounded by lifestyle differences between men and women,” notes Diaz-Sanchez, who was not involved in the study. “The majority of animal models and preclinical studies look at male data, so there is a real need to try to understand the differences between male and female responses.”For the new study, researchers created a vivarium beside a heavily traveled tunnel in Northern California, which allowed for collection and delivery of TRAP into chambers housing male and female rats. Starting at 4 weeks of age, animals were exposed continuously to either tunnel air or filtered air. After about 14 months, the investigators performed histological and biochemical assays to evaluate oxidative stress, inflammation, and fibrosis as markers of cardiopulmonary function.Surprisingly, although lungs exposed to TRAP showed formation of black nodules, markers of pulmonary function were not affected. In contrast, cardiac dysfunction markers were elevated in hearts from both males and females exposed to TRAP. “The most important takeaway is that we see pathologic changes in the cardiorespiratory system after chronic exposure to levels of TRAP that are considered safe by the EPA,” says senior author Pamela Lein, a professor in the Department of Molecular Biosciences at the University of California, Davis.Moreover, there were strong sex differences in this response, with female hearts showing greater effects than male hearts. These findings are consistent with emerging epidemiologic data12 that suggest women may be more susceptible to TRAP-related health effects and further support the relevance of this model to the human condition, Lein says.Even though the study presented limitations such as small sample size and lack of direct assessment of cardiopulmonary function, it could open the door for mechanistic studies aimed at understanding the basis for the sex differences observed. Lein concludes that identifying the TRAP constituent that is driving these changes is the logical next step, as it will likely inform necessary changes to air quality regulatory guidelines.     

Uptake of Chemicals through the Skin: An Important Role of Filaggrin Gene Variants

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Environmental chemicals can enter the human body through oral consumption, inhalation, or skin absorption. The latter exposure route may have been underappreciated, according to Karin Broberg, a professor of environmental medicine at the Karolinska Institute and Lund University, Sweden. That is one reason she decided to study the genetic effects on skin permeability for selected chemicals. Broberg and her colleagues recently published the results of their research in Environmental Health Perspectives.1 They reported that common variants of the filaggrin-expressing gene, FLG, were associated with an increased uptake of chemicals through the skin of human volunteers.The variants studied included the four most common “loss of function” (LOF) mutations in northern Europeans, mutations that prevent the proper assembly of filaggrin.2 The researchers also quantified copy number variants (CNVs), or nearly identical repeat sequences (high versus low), in one part of the FLG gene. CNVs may influence filaggrin function even in people who do not carry LOF mutations.3Open in a separate windowFilament-aggregating protein—or filaggrin—plays an important role in the skin’s ability to maintain a strong barrier. Loss-of-function gene mutations can make carriers vulnerable to the transfer of allergens through the skin.4 The same may hold true for the transfer of environmental chemicals. Image: © zefart/Shutterstock.Filaggrin is a large structural protein that contributes to the skin’s barrier role. Its smaller constituent amino acids act as skin softeners and moisturizers and regulate pH levels and water resistance.4 An effect of the FLG gene on dermal uptake of chemicals is supported by observational studies. For example, cross-sectional studies of Danish men have associated LOF mutations in FLG with higher urinary concentrations of phthalates5 and of phenols, parabens, and ultraviolet filters.6 A case–control study of Swedish chimney sweeps associated high CNVs with lower urinary levels of polycyclic aromatic hydrocarbons (PAHs) from soot.7In the new study, 6.5% of 432 genotyped volunteers carried an LOF mutation and were invited to participate in the dermal exposure experiment, along with age-matched controls. The researchers collected preexposure blood and urine samples from 54 individuals (23 FLG mutation carriers, 31 “typical” wild-type carriers). Next, they applied solutions of three chemicals of interest to different areas of the volunteers’ arms. These chemicals were pyrene (a PAH formed by the combustion of organic material8^,9), pyrimethanil (a fungicide commonly used in fruit farming10), and oxybenzone (an ultraviolet light absorber found in many sunscreen products11^,12). After 4 hours of exposure, the participants again provided blood samples and were asked to collect all urine excreted for 48 hours.Wild-type carriers were distinguished by whether they had low or high CNVs. Urinary biomarkers of the three chemicals were analyzed by liquid chromatography–mass spectrometry. The three genotype groups differed widely in the lag time between absorption of each chemical via the skin and excretion in urine. In both mutation and wild-type/low CNV carriers, the lag time was shorter than in wild-type/high CNV carriers.“Our results show that FLG genotypes influence the levels of chemicals that [enter] our body,” says Broberg. “This example of gene–environment interaction requires validation in independent studies but suggests that low CNV carriers may be as susceptible as mutation carriers to a higher uptake.”With up to 10% of European individuals carrying an FLG LOF mutation13 and 30% having low CNVs,3 this is a surprisingly powerful result, says Sara Brown, a professor of dermatology at the University of Edinburgh, United Kingdom, who was not involved in the study.“This is a high-quality, carefully conducted study,” says Brown. The finding is especially compelling, she says, because not only LOF mutations but also the CNV appears to affect uptake of chemicals through the skin. She adds that important next steps include studying non-White ethnicities and testing whether other genes that control the skin’s also affect the penetration of chemicals.Jacob Pontoppidan Thyssen, a professor of dermatology at the University of Copenhagen, Denmark, agrees with Brown on the high quality of the work, although he notes the lack of measured filaggrin levels in the skin. “Future risk assessment should take into account that individuals with genetically impaired skin barriers are more susceptible to the effects of environmental chemicals,” says Thyssen, who also was not involved in the research. “We should also study if and how FLG mutations affect the penetration of topical drugs.”FLG mutations are powerful risk factors for atopic dermatitis3^,14 and related systemic atopic diseases, such as asthma,15 hay fever,16 and food allergies.17 If this gene also modulates the uptake of environmental chemicals during years of exposure, its potentially even broader systemic effects deserve further study, says Brown. She concludes, “This new research provides convincing evidence that common differences in [skin barrier function] affect the absorption of chemicals that are all around us.”     

Reframing the Question: Does Mitochondrial Damage Set the Stage for Future Inflammation?

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In the 1970s, evidence emerged that environmental exposures could damage mitochondria, the primary regulators of cellular energetics.1^,2 More recently, researchers are studying how stressed mitochondria may initiate a signaling cascade that culminates in inflammation. At the center of this increased investigation is a multiprotein complex called the NLRP3 inflammasome.3^,4 The elusive link between environmentally induced mitotoxicity and inflammasome activation is the subject of a new study published in Environmental Health Perspectives.5Inflammation is a vital physiological response to invading agents or stressors, and inflammasomes are major players in this response. These multiprotein complexes sense pathogen- or damage-associated molecular patterns and trigger the release of proinflammatory cytokines that enhance and sustain inflammation.3 Most inflammasomes contain proteins in the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family; among these, the NLRP3 inflammasome is sensitive to the broadest variety of stimuli and has therefore sparked the most research interest.6 Abnormal activation of NLRP3 has been implicated in disorders such as Alzheimer’s and Parkinson’s diseases, diabetes, and atherosclerosis,4 raising huge clinical interest as a drug development target.7Open in a separate windowAn inflammasome is a complex molecule made up of different proteins. Inflammasomes are activated by sensing the presence of viruses, bacteria, particulate matter, and molecules produced by tissue stress. On activation, they mediate the release of proinflammatory cytokines, which help the body clear foreign substances and repair tissue. Abnormal activation of inflammasomes is implicated in a variety of human diseases. Image: © RAMON ANDRADE 3DCIENCIA/Science Source.“This study may lay the foundation for new directions in research examining agents that contribute to disease via mitochondrial function and inflammasome modulation,” says EHP deputy editor B. Paige Lawrence, a professor at the University of Rochester Medical Center. “Being able to connect exposures with specific, measurable molecular pathways helps to inform our understanding of pathways that lead from exposure to disease.”Previous research has linked inflammasome activation to by-products of mitochondrial damage, such as production of reactive oxygen species (ROS) and loss of membrane potential.8^,9^,10 However, it remains unclear whether pollutant exposures directly alter mitochondria or indirectly affect them by other injury to the cell.11National Institute of Environmental Health Sciences (NIEHS) neurotoxicologist Jean Harry, senior author of the present report, says her team set out to clarify this link. “We wanted to separate biological responses from toxicological ones by looking at a specific shift in the ability of the cell to respond to a secondary hit,” she says. To do this, the investigators exposed specialized immune cells called macrophages to tri-organotins, which are prevalent environmental contaminants that have been shown to alter mitochondrial function.12^,13^,14^,15^,16^,17One group of macrophages was activated, or primed, by exposure to bacterial lipopolysaccharide (LPS), and then both primed and unprimed groups were treated with tri-organotin compounds. Two known neurotoxicants, triethyltin bromide (TETBr) and trimethyltin hydroxide (TMTOH), enhanced formation of inflammasome aggregates and release of proinflammatory cytokines in LPS-primed macrophages. These compounds suppressed mitochondrial bioenergetics but did not alter ROS production, demonstrating that inflammasome activation can occur independently of ROS release. In the reverse scenario, however, pre-exposure to TETBr and TMTOH blunted the appropriate macrophage response to proinflammatory LPS.“Overall, I think the study demonstrates that, rather than looking at apical end points, we should reframe the environmental and public health question: How does an exposure modify the system such that we may change a relative risk to something else coming down the pike later?” says Harry. The environmental toxicants were tested at sublethal levels—not high enough to elicit cell death, but sufficient to change the cells’ responses to a secondary insult. Harry says such changes could manifest as an earlier onset of disease, progression of a disease process, or—of particular interest in the context of the current global pandemic—reduced vaccine response. These effects may be seen as two sides of the same coin.“On the one hand, having an underlying chronic inflammatory condition might change my susceptibility to [any] environmental exposures that might act upon the immune system,” Harry says. “On the other hand, a low-level environmental exposure could change how I respond to an immune challenge later.”Matthew Havrda, an assistant professor at the Geisel School of Medicine at Dartmouth, cautions that the generalized suppression of metabolism observed in exposed macrophages may suggest general distress due to lack of adenosine triphosphate (ATP; the energy currency of the cell) and that inflammasome activation could therefore be part of a bigger stress response. Havrda, who was not involved in the current study, suggests that to find the direct link—the molecular smoking gun—scientists should look at whether the response elicited by tri-organotin exposure is specific to NLRP3. “[NLRP3] drugs and biomarker assays are out there, so if [NLRP3 activation is] specific for this type of toxic exposure, you could potentially screen and treat people to circumvent the deleterious effects,” he says.Harry agrees, noting that inflammasome-blocking drugs currently in development may simply be blocking ATP release and that the specificity of the inflammasome response calls for further studies. She adds that the role of inflammasome aggregate formation should also be clarified. “These aggregates are very sticky and hard to break up, and they have a major stimulatory effect on [surrounding] macrophages, so the acute inflammatory response elicited by environmental exposures may have long-term consequences through the release of those aggregates,” she says. Recent studies18 have proposed these aggregates may act as scaffolds in the formation of plaques in Alzheimer’s disease, supporting the need for further investigation.     

The P-Sufficient Approach: A Strategy for Regulating PFAS as a Class

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Because of concerns about their persistence and potential toxicity, certain per- and polyfluoroalkyl substances (PFAS) have been targeted for regulation or removal from commerce.1^,2 Yet experts worry that regulations aimed at specific PFAS will lead to problems with “regrettable substitutions” in which a regulated chemical is replaced with an unregulated one that may be equally or even more toxic.1 In a commentary published in Environmental Health Perspectives, members of the Safer Consumer Products Program at the California Department of Toxic Substances Control (DTSC) elucidated the scientific rationale for a novel regulatory approach—regulating PFAS chemicals as a class.3PFAS are a group of manmade chemicals that have been used widely over the past several decades in industrial applications, commercial household products, and food packaging.4 Numerous studies suggest that exposure to certain PFAS may be harmful to human health and the health of other organisms, although much remains to be learned.5 “There are six thousand or so PFAS chemicals,6 and the majority have not been thoroughly evaluated for ecological and human toxicity,” says André Algazi, senior study author and chief of the DTSC Chemical-Product Evaluation Section.Open in a separate windowGreaseproof paper food packaging can expose people to PFAS if the chemicals migrate into the packaged food. But discarded products present other exposure opportunities. For instance, depending on the disposal method, packaging can release PFAS into compost, landfill leachate, or (if incinerated) the air. In addition, recycled products made from PFAS-treated paper can be a source of PFAS exposure.10 Image: © onajourney/Shutterstock.PFAS are an extremely diverse group of substances with a wide range of properties and applications, but they all have one thing in common: Somewhere in their chemical structure, each contains at least one carbon chain that is fully fluorinated, meaning it contains only carbon–fluorine bonds. A carbon–fluorine bond is one of the strongest chemical bonds known and thus one of the hardest to break. It is what makes PFAS so resistant to degradation in the environment, explains Ian Cousins, an environmental chemist at Stockholm University in Sweden, who was not involved in the new commentary.Cousins and other environmental scientists have advocated for a persistence-sufficient, or “P-sufficient,” approach to regulating PFAS.7 The idea behind the P-sufficient approach is that the persistence of PFAS is a sufficient basis to warrant regulation regardless of, say, the chemicals’ bioaccumulation potential or toxicity.7 That is different from most chemical regulatory approaches, which tend to focus on hazard traits, such as whether a chemical is suspected or known to cause adverse health effects, Cousins explains. “We know that if we keep emitting PFAS, their concentrations in the environment will increase, because they do not degrade, and ultimately some known or unknown ‘effects threshold’ will be breached. But because there are thousands of PFAS chemicals and we have inadequate toxicity data on most of them, we do not know what the long-term effects will be,” he says.Lead commentary author Simona Bălan, senior environmental scientist at the DTSC, says the California agency is the first in the world to adopt a P-sufficient approach to PFAS. The DTSC has proposed using this new approach to regulate PFAS specifically in food packaging, carpets and rugs, and stain-proofing treatments used on clothing, upholstery, and other consumer textiles.8 Bălan explains these product categories represent some of the biggest sources of documented PFAS exposure. The regulations are expected to be finalized by July 2021. Industry trade groups, including the American Chemistry Council (ACC), argue against a class approach to regulation. Although the total number of PFAS may be large, only a “small fraction” of these substances are actually used in a given application, such as textile treatment products, wrote ACC representative Renée M. Lani in comments to the DTSC on the proposed regulations.9Under the new regulations, manufacturers selling those products on the California market will notify the DTSC of any PFAS used in the product. If a product contains PFAS, the manufacturer will perform an alternatives analysis to determine if a non-PFAS chemical could serve the same function in the product. If a suitable alternative does not exist, the product may continue to be sold, but it will carry a warning label for consumers. “The purpose of the new regulations is to [help] prevent regrettable substitutions, not to put an immediate ban on PFAS in those products,” Bălan says.She and Algazi say these state regulations are just one small step to moving the consumer products market away from persistent chemicals. A P-sufficient approach to PFAS could also be feasible in regulations of drinking water and other environmental media, Algazi adds—for instance, by setting a limit for total allowable PFAS in drinking water. In addition, the authors wrote that other chemical classes may lend themselves to the P-sufficient approach, including nonylphenol ethoxylates in laundry detergents and microplastics.3Although many environmental scientists believe a P-sufficient approach is a step in the right direction when it comes to PFAS,7 it does not completely solve the problem of regrettable substitutions. “Just because something is nonpersistent, doesn’t mean that it is safe,” Cousins says. “A lot more research is needed to determine whether alternatives are better and safer, and what ‘better and safer’ means.”     

Addressing Reemergence of Diphtheria among Adolescents through Program Integration in India

We report a diphtheria outbreak mostly among children (median 12 years; range 4–26 years) of a religious minority in urban India. Case-fatality rate (15%, 19/124) was higher among unimmunized patients (relative risk 4.1, 95% CI 1.5–11.7). We recommend mandating and integrating immunization into school health programs to prevent reemergence. Key words: adolescents, bacteria, children, Corynebacterium diphtheriae, diphtheria, disease outbreaks, evidence-based recommendations, immunization, vaccine-preventable diseases, zoonoses, vaccines

Diphtheria is a vaccine-preventable disease of the upper respiratory system caused by toxigenic strains of Corynebacterium diphtheriae. Global case-fatality rate (CFR) is estimated at 5%–10%; higher CFRs of up to 20% are reported in children <5 years of age (1). In 2016, with 78% national coverage for third-dose diphtheria-tetanus-pertussis (DTP) vaccine, India reported 48% of diphtheria cases and half of 350 deaths worldwide (2,3). In India, the 3 primary DTP doses are administered at 6, 10, and 14 weeks of age, and booster doses are given at 16–24 months and 5–6 years of age. Numerous states across India have reported diphtheria outbreaks, including Assam in 2010, Karnataka in 2011, and Andhra Pradesh in 2014 (4). In December 2017, the Integrated Disease Surveillance Program of Telangana state reported a rise in diphtheria cases. We investigated to describe the epidemiology of the outbreak, identify risk factors, assess trends in immunization coverage, and provide evidence-based recommendations.     

From the Ground up: Assessing Bacterial Diversity in the Air Space of an Urban Park

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Emerging research has linked exposure to diverse airborne microbial communities to healthy human immune systems.1 But few studies have examined how communities of airborne microbes (aerobiomes) vary over time and space2; none are known to have investigated whether these communities change with height from the ground. A recent proof-of-concept study in Environmental Health Perspectives described how the diversity of airborne bacterial communities decreased from ground level to 2m in height in an urban park, noting that the makeup of the communities also varied, depending on height.3“Exposure to a diverse set of microbes from our environment trains our immune systems to respond appropriately to pathogens,” says Graham Rook, a professor of medical microbiology at University College London who was not involved in the study. Lack of exposure to bacterial diversity has been associated with autoimmune diseases,4 allergies,5 Alzheimer’s disease,6 and inflammatory bowel disease.7Open in a separate windowVertical stratification sampling stations captured a snapshot of bacterial diversity at different heights from the ground. Image: Robinson et al. (2020); DOI: 10.1289/EHP7807.Airborne microbial communities are important for human health because our skin and mucous membranes are exposed to them every day.8 Yet the community structure of the aerobiome remains little known, says lead study author Jake Robinson, a doctoral student in microbial ecology at England’s University of Sheffield. An earlier study comparing forest and grassland areas found that elements of the local environment likely drive aerobiome structure.9 “But we wanted to know how the airborne bacterial communities varied over vertical space because, due to height differences, children may be exposed to different microbes than adults,” Robinson says.He and his team chose an urban park in Adelaide, Australia, that consists of about 700 hectares of gardens, woodlands, and playing fields. The researchers set up sampling stations in three randomly selected plots of scrub habitat, defined as parkland with semi-mature trees. At each station, they constructed a stand resembling a hat rack with petri dishes mounted at ground level and at 0.5, 1, and 2m above the ground. These levels were chosen to roughly represent the height of a jogging stroller, a 4-year-old child, and an adult, respectively.On three different days the team left the petri dishes open for 6–8 hours to passively sample the aerobiome. They also collected soil samples. The environmental conditions during the sampling were warm and dry.Back in the lab, the researchers extracted DNA from the samples and amplified the region coding for the 16S rRNA gene. This gene is present across all bacteria and can be used to distinguish between different organisms.10 Software tools clustered the millions of gene sequences and taxonomically identified sequences down to the level of bacterial genus. To quantify bacterial diversity, the team used the Shannon Diversity Index, which uses both species richness (the number of species in a population) and species evenness (the abundance of each species in a population).11The index scores declined by roughly one-third from soil level to 2m above ground. The highest score was found in one of the soil samples. Genera that occurred in both air and soil tended to decline with height above ground. Approximately 84% of taxa in the lower air samples and 76% of upper air taxa were also found in soil. In addition, the community composition of bacterial genera varied widely at different heights. The investigators estimated that sampling height explained 22% of the variation in aerobiome makeup in the study.Notably, this study sampled a small area for only 3 days and did not analyze bacterial DNA down to the level of species and strain. That information would be important “in order to determine whether the organisms they were looking at are the ones that might end up in our guts,” Rook says. In addition, aerobiomes vary across habitat types, different weather conditions (e.g., windy vs. calm days), and concurrent activity levels (e.g., kicking a ball vs. sitting).“The finding that microbial communities vary with height is important because we breathe hundreds of millions of microbes every day,” says Emily Flies, a research fellow in health ecology at the University of Tasmania in Australia. “That exposure during early development is crucial to children’s immune systems. But most aerobiome sampling is done at two meters above ground, so this study indicates that if we want to research what kids are breathing, we need to be sampling at half a meter above ground.”Flies adds that, with more research on how microbial exposure translates to health, investigators may find ways to optimize human exposure to health-promoting biodiverse microbes in greenspaces. This study suggests that greenspaces where people can sit or lie on the ground might facilitate more biodiverse microbial exposures, she says, but further research is needed to confirm these findings and to determine whether and how those microbial exposures affect human health.     

A Right-to-Health Lens on Perinatal Mental Health Care in South Africa

South African women experience some of the highest rates of depression and anxiety globally. Despite South Africa’s laudable human rights commitments to mental health in law, perinatal women are at high risk of common mental disorders due to socioeconomic factors, and they may lack access to mental health services. We used a right to mental health framework, paired with qualitative methods, to investigate barriers to accessing perinatal mental health care. Based on in-depth interviews with 14 key informants in South Africa, we found that (1) physical health was prioritized over mental health at the clinic level; (2) there were insufficient numbers of antenatal and mental health providers to ensure minimum essential levels of perinatal mental health services; (3) the implementation of human rights-based mental health policy has been inadequate; (4) the social determinants were absent from the clinic-level approach to mental health; and (5) a lack of context-specific provider training and support has undermined the quality of mental health promotion and care. We offer recommendations to address these barriers and improve approaches to perinatal mental health screening and care, guided by the following elements of the right to mental health: progressive realization; availability and accessibility; and acceptability and quality.

The Sustainable Development Goals (SDGs), adopted by the United Nations General Assembly in 2015, included the promotion of mental health on the global development agenda for the first time, signaling the rise of mental health as a policy priority for the global community.¹ Mental health remains a significant human rights concern that negatively affects a large number of women globally. Depression, for example, is a leading cause of disability worldwide; approximately 264 million people live with depression, and more women than men are affected.²Common perinatal mental disorders, including depression and anxiety, during and after pregnancy affect an estimated 10%–13% of women in high-income countries and 15.6%–19.8% of women in low- and middle-income countries.³ Prevalence estimates vary greatly across contexts, in part because they depend on how researchers define the perinatal period and whether they use screening or diagnostic data to estimate prevalence.⁴ Mental illness, especially in perinatal women, affects women’s capacity to work, interact with family, fulfill social and community roles, and achieve overall well-being, with detrimental effects for women and their families.⁵ Poor mental health in pregnancy, if untreated, also undermines the health of infants, in part through higher risk of prematurity and low birth weight; and, exposure to maternal depression in utero can have lasting negative effects on the developing brain.⁶ Postpartum depression has been linked to poorer emotional regulation in children through less responsive and attuned relationships between mother and child.⁷ There is less attention in the literature to the impacts of maternal anxiety on the child, but research suggests that maternal depression, anxiety, and stress during pregnancy have potential long-term impacts on the baby and mother.⁸Effectively addressing mental health requires a multisectoral approach that includes attention to the social determinants and lived experience of mental health. In his 2019 report, Danius Pūras, United Nations Special Rapporteur on the right of everyone to the highest attainable standard of physical and mental health (right to health), highlights the critical role of the social determinants of mental health—especially relationships and social connection—to realizing the right to mental health.⁹ In addition, the World Health Organization launched QualityRights training and guidance in 2019, which promotes the active engagement of and support for civil society to build capacity among all stakeholders to improve mental health systems and services.¹⁰ Both the Special Rapporteur’s report and the QualityRights initiative emphasize that transforming mental health requires person-centered, human rights-based approaches within and outside the health care sector. For many people, quality mental health care is not available or accessible; and mental disorders, when left untreated, can have significant consequences for one’s quality of life, physical health, and even risk of suicide.South Africa is a highly relevant context for an investigation of perinatal mental health and human rights because South African women experience some of the world’s highest rates of common perinatal mental disorders. Relative to women in high-income countries, they are almost three times as likely to experience mood and anxiety disorders during the perinatal period. The prevalence of women living with or at high risk of depression in South Africa is an estimated 21%–39%, and the prevalence of postnatal depression is an estimated 16%–32%.¹¹ And, according to one recent study, the prevalence of anxiety disorders among South African pregnant women is 23%.¹² Complex biological and social determinants position South African women uniquely for risks of adverse mental health during the perinatal period. The post-apartheid socioeconomic and cultural context, combined with 30% HIV prevalence in pregnant women, high prevalence of food insecurity, and an increasing non-communicable disease burden, increase the risk of poor mental health.¹³ Importantly, the prevalence of intimate partner violence during pregnancy ranges from 15% to 38%. Research in South Africa shows an association between such violence and an increased risk of antenatal anxiety and depression; and an increase in the severity of intimate partner violence is associated with increased depression symptom severity for pregnant and postpartum women.¹⁴ These and other risk factors combine to substantially increase the risk of perinatal mental illness—especially in the absence of rights-based, holistic mental health promotion and access to mental health services.The traditional, still dominant, model for understanding mental disorders is biomedical in orientation, viewing mental disorders as diseases of the brain and rooted in biology, which largely ignores the underlying social determinants of mental health.¹⁵ There is growing evidence, however, to explain the ways in which social determinants shape mental health and how action to promote population mental health, using a rights-based approach at all stages of the life course, could significantly improve physical and mental health.¹⁶ Audrey Chapman stresses the need for more attention to the social determinants of health when focusing on the right to health:

If the human rights community wants to improve the health status and health outcomes throughout the society, as well as to protect the interests of vulnerable and disadvantaged groups, it will need to pay more attention to differences in social, economic, and political status and their underlying causes and mechanisms.¹⁷

South Africa has embraced a human rights approach to mental health in law and established a mental health policy framework, yet struggles to build a “culture of human rights.”¹⁸ Antenatal care attendance in South Africa is high, serving as an entry point to connect women to an array of supports within and outside the health sector, with a focus on comprehensively addressing mental health and well-being.¹⁹ The National Department of Health periodically issues a manual that provides guidance on maternity care in South Africa; the most recent version provides for routine postnatal care, including postnatal visits at 3–6 days and 6 weeks postpartum to assess women’s mood and general well-being.²⁰ Despite these advances, a complex set of mental health determinants persists, contributing to perinatal mental illness among South African women. To address perinatal mental health as a health and human rights concern, we identify the core obligations of the South African government concerning the right to mental health, with a focus on the perinatal period (Table 1). Guided by these core obligations, we then present findings concerning the obstacles to accessing perinatal mental health care based on in-depth interviews with 14 key informants with expertise in perinatal mental health in South Africa. To address the obstacles identified, we recommend a shift toward a more holistic, human rights-based approach that would better realize the right to mental health for perinatal women in South Africa. To that end, we present brief recommendations, communicated by key informants, to advance this shift (Table 2).Table 1Elements of the right to mental health

Tropical Cyclone Exposures and Health: A New Data Set to Assess Associations over Time

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When a tropical cyclone strikes a region, some deaths and injuries may be directly tied to the storm. Drownings may be caused by flooding, and crushing injuries can result from high winds. However, disasters may also impact health through less apparent routes. For example, the psychological stress of losing one’s home could trigger a heart attack in a person with traditional cardiovascular risk factors, says Brooke Anderson, an associate professor of epidemiology at Colorado State University. In a recent paper published in Environmental Health Perspectives, Anderson and colleagues presented an open-source data set to help epidemiologists understand the health risks associated with tropical cyclones across the eastern half of the United States.1Open in a separate windowA new open-source data set will help epidemiologists better estimate excess mortality and morbidity related to cyclone-related hazards, including flooding, high winds, heavy rains, and tornadoes. Image: © iStockphoto/Shmenny50.Forecasting technologies developed over the last several decades have led to better warning and evacuation systems. These systems have dramatically lowered deaths and injuries from direct causes when a terrible storm hits, Anderson says. “What’s been harder to study is how those disasters might affect health through an indirect path, especially when looking at health outcomes—such as a heart attack—that are pretty common outside of the storm,” she says.Some investigators have already begun to study the indirect health impacts of specific tropical cyclones, including Hurricane Maria,2 which struck Puerto Rico and several Caribbean islands in 2017, and Hurricane Sandy,3 which caused damage in the Caribbean and along the U.S. and Canadian coasts in 2012. Similar data sets have been developed for heat waves to compare how community-wide rates of health outcomes change during or after a heat event.4 “We know a fraction of the health impacts of single large hurricanes,” says Marianthi-Anna Kioumourtzoglou, an epidemiologist at Columbia University, “[but] what is the impact on the health of the cumulative exposure to smaller storms for people living in coastal communities?” Kioumourtzoglou was not involved in the study.To create the new cyclone-specific data set, Anderson and colleagues compiled county-level exposure data for four tropical cyclone hazards: peak sustained wind, rainfall, flooding, and tornadoes. The data cover all counties in the eastern half of the United States for all land-falling or near-land Atlantic basin storms between 1988 and 2018. The researchers chose to aggregate exposure data at the county level to facilitate joining them with other county-level health data such as deaths, hospitalizations, and birth outcomes. The county level is also where decisions and policies around disaster preparation and response are often undertaken.As part of a separate research team, Anderson used the open-source package to assess whether tropical cyclone exposures are linked to adverse birth outcomes5 and is currently studying hospitalization risk among the elderly. Kioumourtzoglou is using the data set to study whether health outcomes such as hospitalizations for asthma attacks, heart attacks, or infections go up or down with exposure to tropical cyclone hazards. “There is the potential to take tropical cyclone epidemiology in a powerful new direction,” Kioumourtzoglou says.Yet, there are certain limitations. Some tropical cyclone exposures may be more consistent over large areas than others.6 High winds and rainfall totals, for instance, may be consistent across a county, tornadoes or flooding may be much more localized.1 If a county is very large, maybe only one part of it experiences flooding. Maybe houses in only a few neighborhoods are destroyed by a tornado. “This could lead to issues with exposure misclassification,” Kioumourtzoglou says.This type of big data approach also may not fully account for social vulnerability, says Jennifer Horney, a disaster epidemiologist at the University of Delaware who was not involved in the study. She explains that factors such as people’s housing, their ability to understand warnings and alerts, and access to vehicles should be part of the equation. “Even at the county level,” she says, “disasters impact different groups differently.”     

A Different Kind of Storm: Natech Events in Houston’s Fenceline Communities

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Puffy plumes of steam rise from the Valero refinery in the Houston community of Manchester, merging into the cloudy August sky. An older Hispanic couple sit in their front yard just across from the refinery, eating their lunch, while two scientists sample the air and soil nearby. It is August 2020, one week after Category 4 Hurricane Laura veered right, sparing Houston, the “Energy Capital of the World,” from the devastation Hurricane Harvey wrought 3 years before. But the residents are perpetually in the path of a different kind of storm.Garett Sansom, a research assistant professor of epidemiology at Texas A&M University (TAMU), is here with graduate student Leanne Fawkes. Working closely with local partner Texas Environmental Justice Advocacy Services, their goal is to find out what chemicals the residents of this community are exposed to and how exposures change before and after storm events. “Most of the visual stuff is steam,” Sansom says of Valero’s smokestacks. “It’s the invisible stuff that’s a problem.”Open in a separate windowIn the days following Hurricane Laura, Garett Sansom and Leanne Fawkes of TAMU collected air and soil samples along the streets of Manchester, across the street from Valero’s Houston Refinery. TAMU investigators are working closely with local partner Texas Environmental Justice Advocacy Services to study chemical exposures in the community. All images: © Wendee Nicole.Manchester is one of several majority Hispanic and Black “fenceline” communities along the Houston Ship Channel, home to one-fourth of the world’s refining capacity.1 Fenceline communities lie adjacent to industrial facilities and live with excess pollution levels, health disparities, and often lower-than-average incomes.2 A history of redlining and segregation, along with a lack of zoning laws, has led many people of color to live in the shadow of industry.3^,4^,5Proximity to industrial neighbors puts fenceline communities in a double bind. They not only deal with daily exposure to potentially toxic emissions but also face increased risk of experiencing a so-called natech (“nay-teck”) event.6 Natech events—short for natural hazard–triggered technological disasters—occur when a natural occurrence such as a hurricane or flood leads to infrastructural failures such as a chemical spill or nuclear reactor meltdown.7 Experts interviewed for this story say neither government regulations nor companies’ planning documents are protecting public health from natech events.The TAMU investigators frequently detect benzene—rare in a typical neighborhood—when they sample in Manchester. Today Fawkes gets a benzene reading of 0.036 ppm along with a total volatile organic compound (VOC) reading of 0.5 ppm. VOC levels rise and fall—these chemicals are volatile, after all—but 0.5 ppm “is weird in neighborhoods,” says Sansom.Most of the available health data for benzene have come from occupational settings, Sansom says, where workers are typically healthy, have access to personal protective equipment, and stay on site for a maximum of 8 hours per workday. On the other hand, he says, “If you live in Manchester, you’re a child, and you’re exposed to it twenty-four seven, what does that mean? The truth is, there are no good toxicological models that can totally explain this situation.”Before Laura, chemical facilities in the Greater Houston area had released an estimated 4,400 tons of air pollutants8 beyond what their Clean Air Act permits allow during normal operations. Such “excess emissions” routinely occur as facilities shut down and start back up before and after major weather events.9 And during storms—whether a hurricane or Texas’s February 2021 historic winter storm—fenceline communities stand a greater chance of suffering the harmful consequences of a natech event due to their proximity.Dealing with hazardous emissions and the fear of leaks and explosions are par for the course for Manchester and other fenceline neighborhoods.10 “Do we get scared sometimes? Of course we do. We live next to a refinery,” Cesareo Torres, the older man sitting in the front yard with his wife, says in Spanish. “But what are you going to do? We have a lifetime here. You kind of get acclimated to it.”Open in a separate windowOne of several fenceline communities along the Houston Ship Channel, Manchester is home to 19 facilities representing numerous industries. However, only 7 of these facilities are required to report potential or actual hazardous releases to the U.S. EPA—the others do not reach the reporting threshold set by the agency, although they are very likely emitting hazardous pollutants. Image: Courtesy Union of Concerned Scientists.     

Making It Count: How to Achieve Structural Change with Community-Based Participatory Research Projects

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Low-income communities of color are inequitably burdened with pollution and its related health effects.1 Environmental health researchers sometimes conduct community-based participatory research projects in which residents help design research questions, collect data, and interpret results.2 Such collaboration often improves the academic rigor of these studies3 and helps inform residents of health risks.4 But does it actually bring about systemic change to economic, social, and political structures? The authors of a review in Environmental Health Perspectives sought to answer that question.5Open in a separate windowThe authors of the new review discussed examples of community-based participatory research projects that successfully effected change. In one, members of the Crow Environmental Health Steering Committee at Little Big Horn College partnered with Montana State University to study contaminants in well water on the Apsaálooke (Crow) Reservation. Crow members of the team (including graduate student Emery Three Irons, shown sampling tap water) used culturally appropriate methods to collect samples and educate fellow Tribal members about the risks of drinking contaminated water. Ultimately, says investigator Margaret Eggers, the best intervention has been to provide free home water coolers that dispense safe drinking water from 5-gallon refillable jugs. Image: Courtesy John Doyle (Apsaálooke)/Little Big Horn College.“I was interviewing community members, and some of their stories just kind of got to me,” says Leona Davis, the lead author of the review. A graduate student in environmental education, Davis was helping Mónica Ramírez-Andreotta, an environmental health science professor and one of her advisors at the University of Arizona, evaluate learning and outcomes of a cocreated citizen science program with disadvantaged communities in Arizona. One of these was Hayden, Arizona, a majority Latino town that is home to a copper smelter and piles of mine tailings.6 Although Davis recognized the residents’ environmental science literacy, she was struck by the glaring injustice of their situation. “I just remember … reflecting that this is a bigger issue than a lack of understanding of science,” says Davis.Davis and Ramírez-Andreotta reviewed the literature to investigate which specific study design elements prompt structural change to benefit overburdened communities. They found that 26 of the 154 case studies they examined resulted in structural change, which they defined as “affecting macro- or meso-level determinants of health, such as zoning policy, economic policy, political power, built environment, public service provision, or environmental policy enforcement.”Within those successful case studies, they found policy change was rarely a clear win, Davis says. For instance, in one case study,7 residents were unable to prevent a new waste facility from being built in their neighborhood. Still, they were able to negotiate a reduction in how much waste the facility handled and the removal of a diesel fueling station from the project. They also obtained guarantees that fleet vehicles would run on alternative fuels.The investigators also found that successful projects shared certain characteristics. During initial planning, these projects examined the structures already in place. They were community-directed, and they adopted governance models where community members held formal leadership roles. Hiring community members to serve as project leaders whenever possible is critical, says Ramírez-Andreotta. She explains that by providing a salary and funding for expenses, financial support for grassroots leadership makes it easier for residents—who are often grappling with poverty, illness, and other stressors—to work toward the changes they want to see.In projects that managed to bring about structural change, investigators had also valued the local knowledge and the lived experience of the community residents. They carefully translated the resulting data into a form that was understandable and useful for community members and other stakeholders. They also set policy change as a goal from the outset. Another key characteristic was commitment to a long-term presence in the community, which the authors defined as longer than 4 years. One case study8 examined the Detroit Community–Academic Urban Research Center, which has existed for more than 25 years and engaged in partnerships to address asthma, air quality, heart health, and other environmental health issues.9Those long-term commitments help build trust, something that can be sorely lacking between community members and academics, says Yanna Lambrinidou, co-organizer of the Engineering Ethics and Community Rights Collaborative, a national initiative to institute community rights in participatory research. “I think [the review] holds a mirror up to academics, asking us to reflect on our trustworthiness—on whether our educational, research, and funding structures are adequately designed to support community-led, systemic solutions or if they may at times even stand in the way,” says Lambrinidou, who was not involved with the review. “Environmental justice communities have been voicing concerns for a long time about academics who show up to help,” she continues. “Yet to this day, academia provides no space for these communities to report problems and no mechanism for protecting them from harm.”Davis and Ramírez-Andreotta hope their work will inform a new generation of investigators while acknowledging the steep systemic barriers to structural change. They point to one case study that involved the Aamjiwnaang First Nation community in Canada. For years, the group has collected data and filed numerous complaints about the dozens of surrounding petrochemical and polymer industrial facilities.10 Yet “despite years of formal complaints supported by empirical evidence,” the authors wrote, “the Canadian Ministry of the Environment continues to approve permits for local polluting industries.”Looking at such cases, the two researchers say, raises a deeply troubling reality: “[Injustice] isn’t because [these communities] lack understanding or education or resources,” says Davis. “It’s the belief that … some people deserve to be the dumping grounds of others. And so even the most robust data set or the snazziest data communication campaign is not going to shake that. You need additional tools.” The authors conclude that project designs that include decision makers and policy goals, as well as increased hiring of faculty of color who can potentially serve as “cultural knowledge brokers,” may be just such tools.     

Walking on a Redline: Did Discriminatory U.S. Housing Policies Affect Greenspace Development?

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Nearly a century ago, a New Deal–era U.S. federal agency developed a color-coding method for mortgage lenders to evaluate the worthiness of neighborhoods across the country. The Home Owners’ Loan Corporation (HOLC) considered characteristics such as racial/ethnic makeup of neighborhoods, age and condition of housing, and access to public services when they evaluated the possible risk to lenders.1 People were systematically denied loans to buy homes or businesses in high-risk “redlined” neighborhoods, and what followed were decades of neglect and disinvestment. Even though redlining as a policy was outlawed in the late 1960s,2 it continues to have not only a social and economic impact on communities, but also an environmental health one.3 A recent study in Environmental Health Perspectives offers new data about the legacy of redlining in American cities and its relationship to greenspace development.4Open in a separate windowThis 1933 map of Birmingham, Alabama, demonstrates the color-coding system10 used by the HOLC to determine the riskiness of making loans for properties in certain neighborhoods. Wealthy White neighborhoods were marked in green and given an A (“best”) grade as the safest investments. Blue B neighborhoods were deemed “still desirable,” although less so, whereas neighborhoods with a lot of recent immigrants might get a yellow C (“declining”) grade. Low-income, ethnically diverse neighborhoods were outlined in red and rated D (“hazardous” to lenders). This particular map includes an additional designation separate from the HOLC system: solid gray for areas with a “Negro concentration.” Cross-hatching indicates industrial and commercial areas, and diagonal lines indicate undeveloped property. Image: Courtesy U.S. National Archives.Anthony Nardone, lead author of the new study and a student in the Joint Medical Program at the University of California, Berkeley, and University of California, San Francisco, says the paper emerged from research that he and his colleagues were conducting on asthma5 and birth outcomes6 in historically redlined communities. “When we were hypothesizing the reasons as to why current outcomes are worse in these places today, one of the things that kept coming up was just the actual physical built environment,” says Nardone. In many of the historically redlined areas, the land was more often covered by impervious surfaces like asphalt and sidewalks, and the neighborhoods had a dearth of parks and trees.7Nardone and his colleagues knew they could simply overlay the original HOLC maps with more recent satellite imagery of neighborhood vegetation, but they wanted to probe any potential associations more deeply by controlling for other sociodemographic factors, such as the racial composition of neighborhoods, median home values, and number of employed people. They mined demographic data from the 1940 U.S. Census and used machine learning to calculate multiple propensity scores to estimate the likelihood that a neighborhood would have been assigned a particular grade.“We tried to compare groups that were similar like you would in a randomized controlled trial, where you try to take two groups that are essentially identical in every which way except for the treatment,” says Nardone. In this way, they could compare C neighborhoods that could have just as well been graded D, or B neighborhoods that might have been graded A.The results showed that neighborhoods that had lower HOLC grades in the past tended to have fewer green resources like parks and trees in the present day. This was true even when controlling for historical demographic factors. Nardone says the results help quantify how the federal government and the banking industry were “able to use their power to funnel well-being and health-generating resources to predominantly White neighborhoods.”That argument piques the interest of Lonnie Hannon, an associate professor of sociology at Tuskegee University who was not involved in the new study. He says this new study is useful in making a case that past discriminatory policies are still having a deleterious impact on Black communities decades later. “If we start with the premise that greenspace enhances health behavior,” he says, “this historical racism that has occurred over the years also leads to deficits in health behavior among current residents of these areas.” In other words, people with reduced access to greenspaces today are typically from the same racial/ethnic groups that experienced redlining. He concludes, “These ‘consequences of place’ manifest as poor health outcomes.”Vivek Shandas, a professor of urban studies and planning at Portland State University who coauthored a study8 on redlining and urban heat in 2020, says that although we have long known that there is a general association between redlining and greenspace, this study offers more proof. “This paper helps us validate and more explicitly articulate the impacts of HOLC redlining policies on the presence of greenspace across these grades,” says Shandas, who was not involved in the new work. “It has the kind of systematic analysis that would help anybody make a clear case that redlining had an effect on the presence of anything green in those specific neighborhoods.”Mixed evidence suggests associations between access to greenspace and improvements in mental health, cardiovascular health, birth outcomes, and child development.9 For Nardone, the issue of greenspace access is a key part of his other health-related research. “We know there are racial health disparities here in the United States, some quite drastic,” he says. He hopes that as policy makers see more evidence for how historical policies of discrimination contributed to these problems, they will be more willing to find solutions.     

First-Trimester Working Conditions and Birthweight: A Prospective Cohort Study

Objectives. We investigated the relationship between women''s first-trimester working conditions and infant birthweight.Methods. Pregnant women (N = 8266) participating in the Amsterdam Born Children and Their Development study completed a questionnaire gathering information on employment and working conditions. After exclusions, 7135 women remained in our analyses. Low birthweight and delivery of a small-for-gestational-age (SGA) infant were the main outcome measures.Results. After adjustment, a workweek of 32 hours or more (mean birthweight decrease of 43 g) and high job strain (mean birthweight decrease of 72 g) were significantly associated with birthweight. Only high job strain increased the risk of delivering an SGA infant (odds ratio [OR] = 1.5; 95% confidence interval [CI] = 1.1, 2.2). After adjustment, the combination of high job strain and a long workweek resulted in the largest birthweight reduction (150 g) and the highest risk of delivering an SGA infant (OR = 2.0; 95% CI = 1.2, 3.2).Conclusions. High levels of job strain during early pregnancy are associated with reduced birthweight and an increased risk of delivering an SGA infant, particularly if mothers work 32 or more hours per week.Delivery of a low-birthweight or small-for-gestational-age (SGA) infant as a result of fetal growth restriction is one of the principal adverse pregnancy outcomes. In the short term, low birthweight and small size for gestational age are major determinants of infant mortality and morbidity¹ and impaired neonatal development.² In the long term, they increase metabolic and cardiovascular disease risk.^3–5 Prevention of fetal growth restriction is therefore of undisputed clinical and economic importance.Maternal factors, obstetric factors (e.g., placental dynamics), and social factors,⁵ including employment-related factors, can all play a role in fetal growth impairment.^6–24 Although employment in general is associated with enhanced outcomes,^6,20,21 certain working conditions represent potential risk factors for the mother and child. Increased levels of risk resulting from long working hours,^{12,13,17,18,24} high physical workloads,^13–16 prolonged standing,^13,18 and psychosocial job strain^7,9,10,24 have been suggested, but the findings in this area are not unequivocal.^8,11,22,23 So far, 2 reviews have been conducted that focused on physical workload and delivery of an SGA infant. Mozurkewich et al.¹⁶ concluded from their review of 29 studies that physically demanding work is associated with SGA births (pooled odds ratio [OR] = 1.37; 95% confidence interval [CI] = 1.30, 1.44). Bonzini et al.¹⁹ reached the same conclusion in their study. To our knowledge, job strain has not been considered in any published review.Limitations in research designs,^6,8,19–21 variability in definitions and measurement of work-related factors,^6,18–20 and true variability across countries and cultures may account for the inconsistent results observed to date. Another important limitation of occupational hazard research is the focus on third-trimester exposures.^11,13 Experimental data and emerging theory point to the first rather than the second or third trimester as a crucial period for regulating the relevant fetal hormonal set points, in particular the hypothalamic pituitary axis (HPA).^25–27 Stress-dependent dysregulation of the HPA affects birthweight and a child''s subsequent growth and development.^25–31 From this perspective, employment during pregnancy is perhaps the most prevalent potential stress factor, given that few working women quit their jobs early in pregnancy.In an effort to overcome the limitations of previous studies, we explored the association between infant birthweight and employment-related conditions (e.g., hours worked per week, hours standing or walking, physical demands of work, and job strain) in an unselected urban cohort of pregnant women. We hypothesized that after adjustment for all known major cofactors, first-trimester work-related effects on birthweight would exceed the third-trimester effects reported in previous research.     

Bacterial Bloodstream Infections in HIV-infected Adults Attending a Lagos Teaching Hospital

An investigation was carried out during October 2005–September 2006 to determine the prevalence of bloodstream infections in patients attending the outpatient department of the HIV/AIDS clinic at the Lagos University Teaching Hospital in Nigeria. Two hundred and one patients—86 males and 115 females—aged 14-65 years were recruited for the study. Serological diagnosis was carried out on them to confirm their HIV status. Their CD4 counts were done using the micromagnetic bead method. Twenty mL of venous blood sample collected from each patient was inoculated into a pair of Oxoid Signal blood culture bottles for 2-14 days. Thereafter, 0.1 mL of the sample was plated in duplicates on MacConkey, blood and chocolate agar media and incubated at 37 °C for 18-24 hours. The CD4+ counts were generally low as 67% of 140 patients sampled had <200 cells/μL of blood. Twenty-six bacterial isolates were obtained from the blood samples and comprised 15 (58%) coagulase-negative staphylococci as follows: Staphylococcus epidermidis (7), S. cohnii cohnii (1), S. cohnii urealyticum (2), S. chromogenes (1), S. warneri (2), S. scuri (1), and S. xylosus (1). Others were 6 (23%) Gram-negative non-typhoid Salmonella spp., S. Typhimurium (4), S. Enteritidis (2); Pseudomonas fluorescens (1), Escherichia coli (1), Ochrobactrum anthropi (1), Moraxella sp. (1), and Chryseobacterium meningosepticum. Results of antimicrobial susceptibility tests showed that coagulase-negative staphylococci had good sensitivities to vancomycin and most other antibiotics screened but were resistant mainly to ampicilin and tetracycline. The Gram-negative organisms isolated also showed resistance to ampicillin, tetracycline, chloramphenicol, and septrin. This study demonstrates that co-agulase-negative staphylococci and non-typhoidal Salmonellae are the most common aetiological agents of bacteraemia among HIV-infected adults attending the Lagos University Teaching Hospital, Nigeria. The organisms were resistant to older-generation antibiotics often prescribed in this environment but were sensitive to vancomycin, cefotaxime, cefuroxime, and other new-generation antibiotics.Key words: Bacteraemia, Bacterial infections, HIV, HIV infections, Nigeria     

Racial/ethnic differences in the development of disability among older adults

Objectives. We investigated differences in the development of disability in activities of daily living among non-Hispanic Whites, African Americans, Hispanics interviewed in Spanish, and Hispanics interviewed in English.Methods. We estimated 6-year risk for disability development among 8161 participants 65 years or older and free of baseline disability. We evaluated mediating factors amenable to clinical and public health intervention on racial/ethnic difference.Results. The risk for developing disability among Hispanics interviewed in English was similar to that among Whites (hazard ratio [HR]=0.99; 95% confidence interval [CI] = 0.6, 1.4) but was substantially higher among African Americans (HR=1.6; 95% CI=1.3, 1.9) and Hispanics interviewed in Spanish (HR=1.8; 95% CI=1.4, 2.1). Adjustment for demographics, health, and socioeconomic status reduced a large portion of those disparities (African American adjusted HR=1.1, Spanish-interviewed Hispanic adjusted HR=1.2).Conclusions. Higher risks for developing disability among older African Americans, and Hispanics interviewed in Spanish compared with Whites were largely attenuated by health and socioeconomic differences. Language- and culture-specific programs to increase physical activity and promote weight maintenance may reduce rates of disability in activities of daily living and reduce racial/ethnic disparities in disability.Disability among older adults (those 65 years or older) is a major health issue involving high personal and economic costs. The number of Americans 65 years or older with chronic disability exceeds 7 million.1 Maintaining the quality of life for older adults by delaying disability may be as important as prolonging life.2^,3 Disability is more strongly associated with medical spending than with life expectancy.4^,5 Long-term care expenditures for older people are projected to reach $161 billion per year by 2010, of which two thirds will be paid by government programs.6The composition of the US population is changing. In 2000, 18% of people in the United States spoke a language at home other than English, up from 11% in 1980.7 The fastest-growing part of the older US population comprises minority groups, particularly African Americans and Hispanics.8 As the number of older people belonging to minority groups increases, there are growing public health concerns about racial/ethnic disparities in health outcomes.9 Although overall rates of disability among older Americans have declined over time, racial/ethnic disparities persist.1^,10^–13 The literature on racial/ethnic disparities in disability mostly focuses on African Americans; national studies investigating disability among Hispanics are limited.1^,12^,14^,15Despite the common practice of conducting interviews in languages other than English to allow respondents to participate in their primary language, few national studies have considered the influence of language differences on health outcomes.16 There are known differences in health and mortality related to immigration and acculturation.16^–19 Use of an interview language other than that of the host culture may be a proxy for acculturation and a predictor of future poor health.20^–23 Insight from a broader investigation of risk factors that includes language differences in relation to disparities in the development of disability is essential to the development of population-based public health programs to help maintain independence among older adults.We investigated racial/ethnic differences in disability among people 65 years and older using 6 years of data from the Health and Retirement Study (HRS),24 Finally, we investigated whether factors amenable to public health and policy intervention mediate minority differences in the development of disability among these Medicare-aged adults.     

Obesity Prevention and Diabetes Screening at Local Health Departments

Objectives. We assessed whether local health departments (LHDs) were conducting obesity prevention programs and diabetes screening programs, and we examined associations between LHD characteristics and whether they conducted these programs.Methods. We used the 2005 National Profile of Local Health Departments to conduct a cross-sectional analysis of 2300 LHDs nationwide. We used multivariate logistic regressions to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Results. Approximately 56% of LHDs had obesity prevention programs, 51% had diabetes screening programs, and 34% had both. After controlling for other factors, we found that employing health educators was significantly associated with LHDs conducting obesity prevention programs (OR = 2.08; 95% CI = 1.54, 2.81) and diabetes screening programs (OR = 1.63; 95% CI = 1.23, 2.17). We also found that conducting chronic disease surveillance was significantly associated with LHDs conducting obesity prevention programs (OR = 1.66; 95% CI = 1.26, 2.20) and diabetes screening programs (OR = 2.44; 95% CI = 1.90, 3.15). LHDs with a higher burden of diabetes prevalence were more likely to conduct diabetes screening programs (OR = 1.20; 95% CI = 1.11, 1.31) but not obesity prevention programs.Conclusions. The presence of obesity prevention and diabetes screening programs was significantly associated with LHD structural capacity and general performance. However, the effectiveness and cost-effectiveness of both types of programs remain unknown.The prevalence of obesity among US adults doubled between 1980 and 2004, and the 2005–2006 National Health and Nutrition Examination Survey found that more than 72 million US adults were obese.^1–3 Obesity contributes to many chronic conditions, including type 2 diabetes, hypertension, stroke, heart disease, certain cancers, and arthritis.¹ Of these conditions, type 2 diabetes, the sixth-leading cause of death in the United States,⁴ may be most closely linked to obesity.⁵ The prevalence of diagnosed diabetes among Americans increased from 2.5% in 1980 to 5.5% in 2005.⁶ In 2007, approximately 17.9 million Americans had diagnosed diabetes, and approximately 5.7 million had undiagnosed diabetes.⁷The public health system has traditionally focused on the prevention and control of infectious diseases. However, improved sanitation and hygiene and the wide adoption of antibiotic use and vaccination have made infectious diseases less common. Conversely, chronic diseases, such as heart disease, cancer, and diabetes, have become more prevalent.^8,9 Chronic diseases now account for 7 of 10 US deaths.¹⁰ Thus, public health agencies, including local health departments (LHDs), may be expected to play an expanded role in chronic disease prevention and control, in addition to their traditional role in infectious disease prevention and their recently enhanced role in disaster and emergency response.¹¹ For example, New York City has started a mandatory registry of glycosylated hemoglobin values.¹²There is a need to better understand the public health system''s responses to chronic diseases (e.g., obesity and diabetes). Although many studies have examined characteristics of LHDs and their public health practices,^13–21 little is known about these departments'' obesity and diabetes prevention activities.²² To fill this gap, we assessed whether LHDs in the United States were conducting obesity prevention programs and diabetes screening programs. We used a conceptual framework developed by an expert panel and the Public Health Practice Program Office of the Centers for Disease Control and Prevention²³ to examine the characteristics of LHDs that conducted these programs and to discover associations between those characteristics and whether LHDs conducted the programs.     

Disseminated Infections with Talaromyces marneffei in Non-AIDS Patients Given Monoclonal Antibodies against CD20 and Kinase Inhibitors

Infections with the fungus Talaromyces (formerly Penicillium) marneffei are rare in patients who do not have AIDS. We report disseminated T. marneffei infection in 4 hematology patients without AIDS who received targeted therapy with monoclonal antibodies against CD20 or kinase inhibitors during the past 2 years. Clinicians should be aware of this emerging complication, especially in patients from disease-endemic regions.Talaromyces (formerly Penicillium) marneffei is a pathogenic, thermal dimorphic fungus that causes systemic mycosis in Southeast Asia. T. marneffei infection is characterized by fungal invasion of multiple organ systems, especially blood, bone marrow, skin, lungs, and reticuloendothelial tissues, and is highly fatal, especially when diagnosis and treatment are delayed (1,2). This disease is found predominantly in AIDS patients and occasionally those with cell-mediated immunodeficiencies involving the interleukin-12/interferon-γ (IFN-γ) signaling pathway, such as congenital STAT1 mutations or acquired autoantibodies against IFN-γ (1,3–6). The infection has rarely been reported among hematology patients, including those from disease-endemic regions (7,8). At Queen Mary Hospital in Hong Kong, a 1,600-bed university teaching hospital that has a hematopoietic stem cell transplantation service, where a wide range of invasive fungal infections have been observed (9,10), only 3 cases of T. marneffei infection were encountered in >2,000 hematology patients in the past 20 years, despite the long-standing availability of mycologic culture and serologic testing (7,8,11,12). In contrast, the infection was commonly reported among AIDS patients (13).In the past 2 years, we have been alerted by 4 unprecedented cases of disseminated T. marneffei infection among non-AIDS hematology patients given targeted therapies, including monoclonal antibodies (mAbs) against CD20 and kinase inhibitors, which are being increasingly used in recent years. We report details for these 4 hematology case-patients. The study was approved by the institutional review board of The University of Hong Kong/Hospital Authority Hong Kong West Cluster in Hong Kong.     

The Impact of School Building Conditions on Student Absenteeism in Upstate New York

Objectives. We investigated Upstate New York school building conditions and examined the associations between school absenteeism and building condition problems.Methods. We merged data from the 2005 Building Condition Survey of Upstate New York schools with 2005 New York State Education Department student absenteeism data at the individual school level and evaluated associations between building conditions and absenteeism at or above the 90th percentile.Results. After adjustment for confounders, student absenteeism was associated with visible mold (odds ratio [OR] = 2.22; 95% confidence interval [CI] = 1.34, 3.68), humidity (OR = 3.07; 95% CI = 1.37, 6.89), poor ventilation (OR = 3.10; 95% CI = 1.79, 5.37), vermin (OR = 2.23; 95% CI = 1.32, 3.76), 6 or more individual building condition problems (OR = 2.97; 95% CI = 1.84, 4.79), and building system or structural problems related to these conditions. Schools in lower socioeconomic districts and schools attended by younger students showed the strongest associations between poor building conditions and absenteeism.Conclusions. We found associations between student absenteeism and adverse school building conditions. Future studies should confirm these findings and prioritize strategies for school condition improvements.School building conditions^1–3 and school absenteeism^4–7 have been associated with student health. Asthma is one of the leading causes of student absenteeism,^4,8 and respiratory infections likely account for a substantial fraction of short-term illness-related absenteeism⁸ among children with⁹ and without asthma. Poor building conditions may contribute to these respiratory problems, resulting in greater school absenteeism or poorer performance.^4,8 However, few studies^8,10–14 have evaluated associations between school building conditions and student absenteeism.Several studies have found associations between parent- or caregiver-reported school absenteeism and exposures to adverse environmental conditions at home.^15,16 Although existing literature has suggested associations between building conditions and school absenteeism, few studies have looked specifically at students'' exposures to adverse school building conditions reported by an objective observer, and these were limited to 1 or 2 exposures.^10–14 Furthermore, some prior studies relied on parental report of student absenteeism rather than using objective school records.^10,14Our goal was to build on the knowledge from previous studies by using objective records of students'' exposures to adverse school building conditions and student absenteeism. We had access to information on a broad range of building conditions from many schools and were able to evaluate cumulative effects of exposure to multiple building conditions. Because we sampled from all Upstate New York schools, our results should be generalizable to a wide range of schools. Our specific aim was to evaluate the associations between school absenteeism and poor building conditions among Upstate New York schools.