Outbreak of Norovirus Illness Among Wildfire Evacuation Shelter Populations - Butte and Glenn Counties, California, November 2018.

The Camp Fire, California's deadliest wildfire, began November 8, 2018, and was extinguished November 25 (1). Approximately 1,100 evacuees from the fire sought emergency shelter. On November 10, acute gastroenteritis (AGE) was reported in two evacuation shelters; norovirus illness was suspected, because it is commonly detected in shelter-associated AGE outbreaks. Norovirus is highly contagious and resistant to several disinfectants. Butte County Public Health Department (BCPHD), assisted by the California Department of Public Health (CDPH), initiated active surveillance to identify cases, confirm the etiology, and assess shelter infection prevention and control (IPC) practices to guide recommendations. During November 8-30, a total of 292 patients with AGE were identified among nine evacuation shelters; norovirus was detected in 16 of 17 unique patient stool specimens. Shelter IPC assessments revealed gaps in illness surveillance, isolation practices, cleaning, disinfection, and handwashing. CDPH and BCPHD collaborated with partner agencies to implement AGE screening, institute isolation protocols and 24-hour cleaning services, and promote proper hand hygiene. During disasters with limited resources, damaged infrastructure, and involvement of multiple organizations, establishing shelter disease surveillance and IPC is difficult. However, prioritizing effective surveillance and IPC at shelter activation is necessary to prevent, identify, and contain outbreaks.

Headache Disorders May Be a Risk Factor for the Development of New Onset Hypothyroidism.

OBJECTIVE: To determine whether headache disorders are a risk factor for the development of new onset hypothyroidism. BACKGROUND: Past studies have reported associations between headache disorders and hypothyroidism, but the directionality of the association is unknown. METHODS: This was a longitudinal retrospective cohort study using data from the Fernald Medical Monitoring Program (FMMP). Residents received physical examinations and thyroid function testing every 3 years during the 20 year program. Residents were excluded from the cohort if there was evidence of past thyroid disease or abnormal thyroid function tests at the first office visit. A diagnosis of a headache disorder was established by self-report of "frequent headaches," use of any headache-specific medication, or a physician diagnosis of a headache disorder. The primary outcome measure was new onset hypothyroidism defined as the initiation of thyroid replacement therapy or TSH ≥ 10 without thyroid medication. A Cox survival analysis with time dependent variables were used for the model. Headache disorders, age, sex, body mass index, income, smoking, narcotic use, and hypothyroidism-producing medications were independent variables in the model. RESULTS: Data from 8412 residents enrolled in the FMMP were used in the current study. Headache disorders were present in about 26% of the residents and new onset hypothyroidism developed in ∼7%. The hazard ratio for the development of new onset hypothyroidism was 1.21 (95% CI = 1.001, 1.462) for those with headache disorders. CONCLUSIONS: Headache disorders may be associated with an increased risk for the development of new onset hypothyroidism.

Exposure to Perfluoroalkyl Substances and Associations with Pubertal Onset and Serum Reproductive Hormones in a Longitudinal Study of Young Girls in Greater Cincinnati and the San Francisco Bay Area.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS), endocrine disrupting chemicals with worldwide exposure, cause changes in mammary gland development in rodents. A few human studies report delay in pubertal events with increasing perfluorooctanoic acid (PFOA) exposure, but to our knowledge none have examined reproductive hormone levels at thelarche. METHODS: In a cohort of Greater Cincinnati (GC) and San Francisco Bay Area (SFBA) girls recruited at 6-8 years of age, clinical examinations were conducted annually or semiannually with sequential Tanner staging. PFAS concentrations were measured in the first serum sample of 704 girls. In 304 GC girls, estradiol (E2), estrone (E1), testosterone (T), and dihydroepiandrosterone sulfate (DHEAS) were measured in serum at four time points around puberty. Relationships between PFAS and age at thelarche, pubarche, and menarche were analyzed using survival and structural equation models. The association between PFAS and reproductive hormones was assessed using linear regression models. RESULTS: Median PFOA serum concentrations in GC (N=353, 7.3 ng/mL) and the SFBA (N=351, 5.8 ng/mL) were higher than in the U.S. POPULATION: In multivariable Cox proportional hazard models [adjusted for race, body mass index (BMI)], increasing serum log-transformed PFOA was associated with a delay in pubarche [hazard ratio (HR)=0.83; 95% CI: 0.70, 0.99] and menarche (HR=0.04; 95% CI: 0.01, 0.25). Structural equation models indicated a triangular relationship between PFOA, BMI percentile, and the age at the pubertal milestone. Increased PFOA had a statistically significant direct effect of delay on all three milestones, as did BMI. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (Me-PFOSA-AcOH) also were associated with later thelarche, and Me-PFOSA-AcOH also with later pubarche. PFOA was inversely associated with DHEAS (p<0.01), E1 (p=0.04), and T (p=0.03) concentrations at 6 months prior to puberty. CONCLUSIONS: PFAS may delay pubertal onset through the intervening effects on BMI and reproductive hormones. The decreases in DHEAS and E1 associated with PFOA represent biological biomarkers of effect consistent with the delay in onset of puberty. https://doi.org/10.1289/EHP11811.

A Markov model to estimate Salmonella morbidity, mortality, illness duration, and cost.

Approximately 690000-1790000 Salmonella cases, 20000 hospitalizations, and 400 deaths occur in the USA annually, costing approximately $2.6bn. Existing models estimate morbidity, mortality, and cost solely from incidence. They do not estimate illness duration or use time as an independent cost predictor. Existing models may underestimate physician visits, hospitalizations, deaths, and associated costs. We developed a Markov chain Monte Carlo model to estimate illness duration, physician/emergency room visits, inpatient hospitalizations, mortality, and resultant costs for a given Salmonella incidence. Interested parties include society, third-party payers, health providers, federal, state and local governments, businesses, and individual patients and their families. The marginal approach estimates individual disease behavior for every patient, explicitly estimates disease duration and calculates separate time-dependent costs. The aggregate approach is a Markov equivalent of the existing models; it assumes average disease behavior and cost for a given morbidity/mortality. Transition probabilities were drawn from a meta-analysis of 53 Salmonella studies. Both approaches were tested using the 1993 Salmonella typhimurium outbreak in Gideon, Missouri. This protocol can be applied to estimate morbidity, mortality and cost of specific outbreaks, provide better national Salmonella burden estimates, and estimate the benefits of reducing Salmonella risk.

Comprehension and perceptions of study participants upon receiving perfluoroalkyl substance exposure biomarker results.

BACKGROUND: Measurement of environmental biomarkers in biomedia is increasingly used as a method of exposure characterization in human population studies. Reporting the results of biomarker measurements back to study participants has been controversial, including questions of ethics and whether the study participants would want to receive and would understand the results. METHODS: Recently we mailed individual measurements of two serum biomarkers, perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) to participants in three exposure studies of persons living in the Ohio River Valley, of whom 60 were parents of children who had been sampled. Many had serum concentrations of PFOA above the US population 95th percentile value. Reporting forms used in the three studies were somewhat different (either tables or charts for comparison to US population values) and varied in complexity. With all reports, we included information about concentrations of PFOA and PFOS in the general population, and a survey designed to ascertain the opinions of the study participants about the information they received. RESULTS: Approximately 33% (273/821) returned the survey, and of those, 96% reported that they were pleased that we had sent them the report. Most (86%) responded that the results were easy to understand and the enclosed fact sheet was helpful in answering questions (87%). Regarding the amount of information, most felt that we provided the "right amount" (78%) but some "too much" (7%) and some "too little" (15%). The majority (53%) were surprised at their serum concentrations. Of those with serum values > 13.0 ng/mL, 74% responded that they thought their serum concentration was "high", but only 22% of those with serum concentrations ≤5.6 responded that their concentration was "low". Surprisingly, many talked to no one about their levels; those who did were most likely to discuss the report with family members. CONCLUSIONS: Reporting back individual environmental biomarker results is generally well received by study participants, and those with high concentrations perceived them to be high. Questions remain as to why study participants did not discuss their results with others.

Polyfluoroalkyl substance exposure in the Mid-Ohio River Valley, 1991-2012.

BACKGROUND: Industrial discharges of perfluorooctanoic acid (PFOA) to the Ohio River, contaminating water systems near Parkersburg, WV, were previously associated with nearby residents' serum PFOA concentrations above US general population medians. Ohio River PFOA concentrations downstream are elevated, suggesting Mid-Ohio River Valley residents are exposed through drinking water. OBJECTIVES: Quantify PFOA and 10 other per- and polyfluoroalkyl substances (PFAS) in Mid-Ohio River Valley resident sera collected between 1991 and 2013 and determine whether the Ohio River and Ohio River Aquifer are exposure sources. METHODS: We measured eleven PFAS in 1608 sera from 931 participants. Serum PFOA concentration and water source associations were assessed using linear mixed-effects models. We estimated between-sample serum PFOA using one-compartment pharmacokinetics for participants with multiple samples. RESULTS: In serum samples collected as early as 1991, PFOA (median = 7.6 ng/mL) was detected in 99.9% of sera; 47% had concentrations greater than US population 95th percentiles. Five other PFAS were detected in greater than 82% of samples; median other PFAS concentrations were similar to the US general population. Serum PFOA was significantly associated with water source, sampling year, age at sampling, tap water consumption, pregnancy, gravidity and breastfeeding. Serum PFOA was 40-60% lower with granular activated carbon (GAC) use. Repeated measurements and pharmacokinetics suggest serum PFOA peaked 2000-2006 for participants using water without GAC treatment; where GAC was used, serum PFOA concentrations decreased from 1991 to 2012. CONCLUSIONS: Mid-Ohio River Valley residents appear to have PFOA, but not other PFAS, serum concentrations above US population levels. Drinking water from the Ohio River and Ohio River Aquifer, primarily contaminated by industrial discharges 209-666 km upstream, is likely the primary exposure source. GAC treatment of drinking water mitigates, but does not eliminate, PFOA exposure.

Hypercholesterolemia with consumption of PFOA-laced Western diets is dependent on strain and sex of mice.

Perfluorooctanoic acid (PFOA) is a man-made surfactant with a number of industrial applications. It has a long half-life environmentally and biologically. Past studies suggest a direct relationship between plasma cholesterol and PFOA serum concentrations in humans and an inverse one in rodents fed standard rodent chow, making it difficult to examine mechanisms responsible for the potential PFOA-induced hypercholesterolemia and altered sterol metabolism. To examine dietary modification of PFOA-induced effects, C57BL/6 and BALB/c mice were fed PFOA in a fat- and cholesterol-containing diet. When fed these high fat diets, PFOA ingestion resulted in marked hypercholesterolemia in male and female C57BL/6 mice and less robust hypercholesterolemia in male BALB/c mice. The PFOA-induced hypercholesterolemia appeared to be the result of increased liver masses and altered expression of genes associated with hepatic sterol output, specifically bile acid production. mRNA levels of genes associated with sterol input were reduced only in C57BL/6 females, the mice with the greatest increase in plasma cholesterol levels. Strain-specific PFOA-induced changes in cholesterol concentrations in mammary tissues and ovaries paralleled changes in plasma cholesterol levels. mRNA levels of sterol-related genes were reduced in ovaries of C57BL/6 but not in BALB/c mice and not in mammary tissues. Our data suggest that PFOA ingestion leads to hypercholesterolemia in mice fed fat and cholesterol and effects are dependent upon the genetic background and gender of the mice with C57BL/6 female mice being most responsive to PFOA.

Target animal safety and tolerance study of pyrantel pamoate paste (19.13% w/w pyrantel base) administered orally to horses.

Pyrantel pamoate paste (19.13% w/w pyrantel base) for the treatment of tapeworm, Anoplocephala spp was evaluated for target animal safety and tolerance in horses treated orally at 0, 1, 3, 5, and 10 times the clinical dose of 13.2 mg pyrantel base/kg body weight administered daily for six consecutive days. Parameters evaluated included clinical signs, food and water consumption, body weights, physical examinations, clinical pathology (hematology, coagulation, serum chemistry, urinalyses, and fecal examinations), complete necropsy, organ weights, and histopathology. No adverse events or test article-related effects were observed in any treatment group during daily clinical observations of the test animals. Statistically significant changes (P < .05) lacked a dose- and/or time-dependent trend and were considered incidental. Administration of pyrantel pamoate paste did not produce any macroscopic or microscopic tissue effects in any dose group of either sex. The no-observed-effect-level (NOEL) for pyrantel pamoate paste, when administered orally to horses once daily for 6 consecutive days, was determined to be 132 mg/kg/day. Pyrantel pamoate paste (19.13% w/w pyrantel base) can be safely administered orally to horses at 13.2 mg of pyrantel base/kg for the treatment of Anoplocephala infestations.

Serum biomarkers of polyfluoroalkyl compound exposure in young girls in Greater Cincinnati and the San Francisco Bay Area, USA.

PFC serum concentrations were measured in 6-8 year-old girls in Greater Cincinnati (GC) (N = 353) and the San Francisco Bay Area (SFBA) (N = 351). PFOA median concentration was lower in the SFBA than GC (5.8 vs. 7.3 ng/mL). In GC, 48/51 girls living in one area had PFOA concentrations above the NHANES 95th percentile for children 12-19 years (8.4 ng/mL), median 22.0 ng/mL. The duration of being breast fed was associated with higher serum PFOA at both sites and with higher PFOS, PFHxS and Me-PFOSA-AcOH concentrations in GC. Correlations of the PFC analytes with each other suggest that a source upriver from GC may have contributed to exposures through drinking water, and water treatment with granular activated carbon filtration resulted in less exposure for SWO girls compared to those in NKY. PFOA has been characterized as a drinking water contaminant, and water treatment systems effective in removing PFCs will reduce body burdens.

Onset of breast development in a longitudinal cohort.

BACKGROUND AND OBJECTIVES: There is growing evidence of pubertal maturation occurring at earlier ages, with many studies based on cross-sectional observations. This study examined age at onset of breast development (thelarche), and the impact of BMI and race/ethnicity, in the 3 puberty study sites of the Breast Cancer and the Environment Research Program, a prospective cohort of >1200 girls. METHODS: Girls, 6 to 8 years at enrollment, were followed longitudinally at regular intervals from 2004 to 2011 in 3 geographic areas: the San Francisco Bay Area, Greater Cincinnati, and New York City. Sexual maturity assessment using Tanner staging was conducted by using standardized observation and palpation methods by trained and certified staff. Kaplan-Meier analyses were used to describe age at onset of breast maturation by covariates. RESULTS: The age at onset of breast stage 2 varied by race/ethnicity, BMI at baseline, and site. Median age at onset of breast stage 2 was 8.8, 9.3, 9.7, and 9.7 years for African American, Hispanic, white non-Hispanic, and Asian participants, respectively. Girls with greater BMI reached breast stage 2 at younger ages. Age-specific and standardized prevalence of breast maturation was contrasted to observations in 2 large cross-sectional studies conducted 10 to 20 years earlier (Pediatric Research in Office Settings and National Health and Nutrition Examination Survey III) and found to have occurred earlier among white, non-Hispanic, but not African American girls. CONCLUSIONS: We observed the onset of thelarche at younger ages than previously documented, with important differences associated with race/ethnicity and BMI, confirming and extending patterns seen previously. These findings are consistent with temporal changes in BMI.