Matthew O. Gribble

An Updated Review of Ciguatera Fish Poisoning: Clinical, Epidemiological, Environmental, and Public Health Management

Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world. It causes substantial human health, social, and economic impacts. The illness produces a complex array of gastrointestinal, neurological and neuropsychological, and cardiovascular symptoms, which may last days, weeks, or months. This paper is a general review of CFP including the human health effects of exposure to ciguatoxins (CTXs), diagnosis, human pathophysiology of CFP, treatment, detection of CTXs in fish, epidemiology of the illness, global dimensions, prevention, future directions, and recommendations for clinicians and patients. It updates and expands upon the previous review of CFP published by Friedman et al. (2008) and addresses new insights and relevant emerging global themes such as climate and environmental change, international market issues, and socioeconomic impacts of CFP. It also provides a proposed universal case definition for CFP designed to account for the variability in symptom presentation across different geographic regions. Information that is important but unchanged since the previous review has been reiterated. This article is intended for a broad audience, including resource and fishery managers, commercial and recreational fishers, public health officials, medical professionals, and other interested parties.

Association of cardiometabolic genes with arsenic metabolism biomarkers in American Indian communities: The strong heart family study (SHFS)

Background: Metabolism of inorganic arsenic (iAs) is subject to inter-individual variability, which is explained partly by genetic determinants. Objectives: We investigated the association of genetic variants with arsenic species and principal components of arsenic species in the Strong Heart Family Study (SHFS). Methods: We examined variants previously associated with cardiometabolic traits (~ 200,000 from Illumina Cardio MetaboChip) or arsenic metabolism and toxicity (670) among 2,428 American Indian participants in the SHFS. Urine arsenic species were measured by high performance liquid chromatography–inductively coupled plasma mass spectrometry (HPLC-ICP-MS), and percent arsenic species [iAs, monomethylarsonate (MMA), and dimethylarsinate (DMA), divided by their sum × 100] were logit transformed. We created two orthogonal principal components that summarized iAs, MMA, and DMA and were also phenotypes for genetic analyses. Linear regression was performed for each phenotype, dependent on allele dosage of the variant. Models accounted for familial relatedness and were adjusted for age, sex, total arsenic levels, and population stratification. Single nucleotide polymorphism (SNP) associations were stratified by study site and were meta-analyzed. Bonferroni correction was used to account for multiple testing. Results: Variants at 10q24 were statistically significant for all percent arsenic species and principal components of arsenic species. The index SNP for iAs%, MMA%, and DMA% (rs12768205) and for the principal components (rs3740394, rs3740393) were located near AS3MT, whose gene product catalyzes methylation of iAs to MMA and DMA. Among the candidate arsenic variant associations, functional SNPs in AS3MT and 10q24 were most significant (p < 9.33 × 10–5). Conclusions: This hypothesis-driven association study supports the role of common variants in arsenic metabolism, particularly AS3MT and 10q24. Citation: Balakrishnan P, Vaidya D, Franceschini N, Voruganti VS, Gribble MO, Haack K, Laston S, Umans JG, Francesconi KA, Goessler W, North KE, Lee E, Yracheta J, Best LG, MacCluer JW, Kent J Jr., Cole SA, Navas-Acien A. 2017. Association of cardiometabolic genes with arsenic metabolism biomarkers in American Indian communities: the Strong Heart Family Study (SHFS). Environ Health Perspect 125:15–22; http://dx.doi.org/10.1289/EHP251

Arsenic-gene interactions and beta-cell function in the Strong Heart Family Study

ABSTRACT We explored arsenic‐gene interactions influencing pancreatic beta‐cell activity in the Strong Heart Family Study (SHFS). We considered 42 variants selected for associations with either beta‐cell function (31 variants) or arsenic metabolism (11 variants) in the SHFS. Beta‐cell function was calculated as homeostatic model ‐ beta corrected for insulin resistance (cHOMA‐B) by regressing homeostatic model – insulin resistance (HOMA‐IR) on HOMA‐B and adding mean HOMA‐B. Arsenic exposure was dichotomized at the median of the sum of creatinine‐corrected inorganic and organic arsenic species measured by high performance liquid chromatography‐inductively coupled plasma mass spectrometry (HPLC‐ICPMS). Additive GxE models for cHOMA‐B were adjusted for age and ancestry, and accounted for family relationships. Models were stratified by center (Arizona, Oklahoma, North Dakota and South Dakota) and meta‐analyzed. The two interactions between higher vs. lower arsenic and SNPs for cHOMA‐B that were nominally significant at P < 0.05 were with rs10738708 (SNP overall effect −3.91, P = 0.56; interaction effect with arsenic −31.14, P = 0.02) and rs4607517 (SNP overall effect +16.61, P = 0.03; interaction effect with arsenic +27.02, P = 0.03). The corresponding genes GCK and TUSC1 suggest oxidative stress and apoptosis as possible mechanisms for arsenic impacts on beta‐cell function. No interactions were Bonferroni‐significant (1.16 × 10−3). Our findings are suggestive of oligogenic moderation of arsenic impacts on pancreatic &bgr;‐cell endocrine function, but were not Bonferroni‐significant. HighlightsGenetic variants near tumor suppressor TUSC1 may alter arsenic pancreatic toxicity.Genetic variation near glucokinase GCK and secretory protein YKT6 genes may alter arsenic pancreatic toxicity.Additional research on apoptosis and oxidative stress mechanisms is warranted.

Open Defecation Sites, Unmet Sanitation Needs, and Potential Sanitary Risks in Atlanta, Georgia, 2017–2018

Objectives To survey the spatial distribution and enteric pathogen profile of discarded human feces in the city of Atlanta, Georgia. Methods After defining priority search areas in central Atlanta, we conducted 5 searches of open defecation sites totaling 15 hours during the period from October 2017 to January 2018. We collected fresh stools for analysis via multiplex reverse-transcription polymerase chain reaction to identify presence of 15 common parasitic, bacterial, and viral enteric pathogens. Results We identified and mapped 39 open defecation sites containing 118 presumptive human stools; 23% of the 26 collected fresh stools tested positive for 1 or more pathogens. An estimated 12% of stools were positive for enterotoxigenic Escherichia coli, 7.7% for Giardia spp., 3.8% for norovirus, and 3.8% for Salmonella spp. The majority (92%) of identified open defecation sites were within 400 meters of a shelter or soup kitchen. Conclusions Though this study was constrained by a small sample size, results suggest that open defecation in Atlanta is common and may pose risks to public health. Public Health Implications Open defecation may pose health risks to people experiencing homelessness and the general public.

The Sequential Probability Ratio Test: An efficient alternative to exact binomial testing for Clean Water Act 303(d) evaluation

The United Statess Clean Water Act stipulates in section 303(d) that states must identify impaired water bodies for which total maximum daily loads (TMDLs) of pollution inputs into water bodies are developed. Decision-making procedures about how to list, or delist, water bodies as impaired, or not, per Clean Water Act 303(d) differ across states. In states such as California, whether or not a particular monitoring sample suggests that water quality is impaired can be regarded as a binary outcome variable, and Californias current regulatory framework invokes a version of the exact binomial test to consolidate evidence across samples and assess whether the overall water body complies with the Clean Water Act. Here, we contrast the performance of Californias exact binomial test with one potential alternative, the Sequential Probability Ratio Test (SPRT). The SPRT uses a sequential testing framework, testing samples as they become available and evaluating evidence as it emerges, rather than measuring all the samples and calculating a test statistic at the end of the data collection process. Through simulations and theoretical derivations, we demonstrate that the SPRT on average requires fewer samples to be measured to have comparable Type I and Type II error rates as the current fixed-sample binomial test. Policymakers might consider efficient alternatives such as SPRT to current procedure.

Calls to Florida Poison Control Centers about mercury: Trends over 2003–2013

Objective: The aim of this analysis was to contrast trends in exposure‐report calls and informational queries (a measure of public interest) about mercury to the Florida Poison Control Centers over 2003–2013. Materials and methods: Poison‐control specialists coded calls to Florida Poison Control Centers by substance of concern, caller demographics, and whether the call pertained to an exposure event or was an informational query. For the present study, call records regarding mercury were de‐identified and provided along with daily total number of calls for statistical analysis. We fit Poisson models using generalized estimating equations to summarize changes across years in counts of daily calls to Florida Poison Control Centers, adjusting for month. In a second stage of analysis, we further adjusted for the total number of calls each day. We also conducted analyses stratified by age of the exposed. Results: There was an overall decrease over 2003–2013 in the number of total calls about mercury [Ratio per year: 0.89, 95% CI: (0.88, 0.90)], and calls about mercury exposure [Ratio per year: 0.84, 95% CI: (0.83, 0.85)], but the number of informational queries about mercury increased over this time [Ratio per year: 1.15 (95% CI: 1.12, 1.18)]. After adjusting for the number of calls of that type each day (e.g., call volume), the associations remained similar: a ratio of 0.88 (95% CI: 0.87, 0.89) per year for total calls, 0.85 (0.83, 0.86) for exposure‐related calls, and 1.17 (1.14, 1.21) for informational queries. Conclusion: Although, the number of exposure‐related calls decreased, informational queries increased over 2003–2013. This might suggest an increased public interest in mercury health risks despite a decrease in reported exposures over this time period. HighlightsInformational queries about mercury to the Florida Poison Control Centers increased over 2003–2013.Exposure‐related calls about mercury to the Florida Poison Control Centers decreased over 2003–2013.Decreases in exposure‐related calls over 2003–2013 were most pronounced among persons ≥ 60 years old.

Stepped-wedge cluster-randomised controlled trial to assess the cardiovascular health effects of a managed aquifer recharge initiative to reduce drinking water salinity in southwest coastal Bangladesh: study design and rationale

Introduction Saltwater intrusion and salinisation have contributed to drinking water scarcity in many coastal regions globally, leading to dependence on alternative sources for water supply. In southwest coastal Bangladesh, communities have few options but to drink brackish groundwater which has been associated with high blood pressure among the adult population, and pre-eclampsia and gestational hypertension among pregnant women. Managed aquifer recharge (MAR), the purposeful recharge of surface water or rainwater to aquifers to bring hydrological equilibrium, is a potential solution for salinity problem in southwest coastal Bangladesh by creating a freshwater lens within the brackish aquifer. Our study aims to evaluate whether consumption of MAR water improves human health, particularly by reducing blood pressure among communities in coastal Bangladesh. Methods and analysis The study employs a stepped-wedge cluster-randomised controlled community trial design in 16 communities over five monthly visits. During each visit, we will collect data on participants’ source of drinking and cooking water and measure the salinity level and electrical conductivity of household stored water. At each visit, we will also measure the blood pressure of participants ≥20 years of age and pregnant women and collect urine samples for urinary sodium and protein measurements. We will use generalised linear mixed models to determine the association of access to MAR water on blood pressure of the participants. Ethics and dissemination The study protocol has been reviewed and approved by the Institutional Review Boards of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). Informed written consent will be taken from all the participants. This study is funded by Wellcome Trust, UK. The study findings will be disseminated to the government partners, at research conferences and in peer-reviewed journals. Trial registration number NCT02746003; Pre-results.