Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 38 Records) |
Query Trace: Jarrett J[original query] |
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Baseline characteristics including blood and urine metal levels in the Trial to Assess Chelation Therapy 2 (TACT2)
Navas-Acien A , Santella RM , Joubert BR , Huang Z , Lokhnygina Y , Ujueta F , Gurvich I , LoIacono NJ , Ravalli F , Ward CD , Jarrett JM , Salazar AL , Boineau R , Jones TLZ , Mark DB , Newman JD , Nathan DM , Anstrom KJ , Lamas GA . Am Heart J 2024 BACKGROUND: The reduction in cardiovascular disease (CVD) events with edetate disodium (EDTA) in the Trial to Assess Chelation Therapy (TACT) suggested that chelation of toxic metals might provide novel opportunities to reduce CVD in patients with diabetes. Lead and cadmium are vasculotoxic metals chelated by EDTA. We present baseline characteristics for participants in TACT2, a randomized, double-masked, placebo-controlled trial designed as a replication of the TACT trial limited to patients with diabetes. METHODS: TACT2 enrolled 1,000 participants with diabetes and prior myocardial infarction, age 50 years or older between September 2016 and December 2020. Among 959 participants with at least one infusion, 933 had blood and/or urine metals measured at the Centers for Diseases Control and Prevention using the same methodology as in the National Health and Nutrition Examination Survey (NHANES). We compared metal levels in TACT2 to a contemporaneous subset of NHANES participants with CVD, diabetes and other inclusion criteria similar to TACT2's participants. RESULTS: At baseline, the median (interquartile range, IQR) age was 67 (60, 72) years, 27% were women, 78% reported white race, mean (SD) BMI was 32.7 (6.6) kg/m(2), 4% reported type 1 diabetes, 46.8% were treated with insulin, 22.3% with GLP1-receptor agonists or SGLT-2 inhibitors, 90.2% with aspirin, warfarin or P2Y12 inhibitors, and 86.5% with statins. Blood lead was detectable in all participants; median (IQR) was 9.19 (6.30, 13.9) μg/L. Blood and urine cadmium were detectable in 97% and median (IQR) levels were 0.28 (0.18, 0.43) μg/L and 0.30 (0.18, 0.51) μg/g creatinine, respectively. Metal levels were largely similar to those in the contemporaneous NHANES subset. CONCLUSIONS: TACT2 participants were characterized by high use of medication to treat CVD and diabetes and similar baseline metal levels as in the general US population. TACT2 will determine whether chelation therapy reduces the occurrence of subsequent CVD events in this high-risk population. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov. Identifier: NCT02733185. https://clinicaltrials.gov/study/NCT02733185. |
The contribution of declines in blood lead levels to reductions in blood pressure levels: Longitudinal evidence in the Strong Heart Family Study
Lieberman-Cribbin W , Li Z , Lewin M , Ruiz P , Jarrett JM , Cole SA , Kupsco A , O'Leary M , Pichler G , Shimbo D , Devereux RB , Umans JG , Navas-Acien A , Nigra AE . J Am Heart Assoc 2024 13 (2) e031256 BACKGROUND: Chronic lead exposure is associated with both subclinical and clinical cardiovascular disease. We evaluated whether declines in blood lead were associated with changes in systolic and diastolic blood pressure in adult American Indian participants from the SHFS (Strong Heart Family Study). METHODS AND RESULTS: Lead in whole blood was measured in 285 SHFS participants in 1997 to 1999 and 2006 to 2009. Blood pressure and measures of cardiac geometry and function were obtained in 2001 to 2003 and 2006 to 2009. We used generalized estimating equations to evaluate the association of declines in blood lead with changes in blood pressure; cardiac function and geometry measures were considered secondary. Mean blood lead was 2.04 μg/dL at baseline. After ≈10 years, mean decline in blood lead was 0.67 μg/dL. In fully adjusted models, the mean difference in systolic blood pressure comparing the highest to lowest tertile of decline (>0.91 versus <0.27 μg/dL) in blood lead was -7.08 mm Hg (95% CI, -13.16 to -1.00). A significant nonlinear association between declines in blood lead and declines in systolic blood pressure was detected, with significant linear associations where blood lead decline was 0.1 μg/dL or higher. Declines in blood lead were nonsignificantly associated with declines in diastolic blood pressure and significantly associated with declines in interventricular septum thickness. CONCLUSIONS: Declines in blood lead levels in American Indian adults, even when small (0.1-1.0 μg/dL), were associated with reductions in systolic blood pressure. These findings suggest the need to further study the cardiovascular impacts of reducing lead exposures and the importance of lead exposure prevention. |
Influence of half-life and smoking/nonsmoking ratio on biomarker consistency between Waves 1 and 2 of the Population Assessment of Tobacco and Health Study
Ashley DL , Zhu W , Bhandari D , Wang L , Feng J , Wang Y , Meng L , Xia B , Jarrett JM , Chang CM , Kimmel HL , Blount BC . Cancer Epidemiol Biomarkers Prev 2023 33 (1) 80-87 BACKGROUND: Biomarkers of exposure are tools for understanding the impact of tobacco use on health outcomes if confounders like demographics, use behavior, biological half-life and other sources of exposure are accounted for in the analysis. METHODS: We performed multiple regression analysis of longitudinal measures of urinary biomarkers of alkaloids, tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, volatile organic compounds (VOC), and metals to examine the sample-to-sample consistency in Waves 1 and 2 of the Population Assessment of Tobacco and Health Study including demographic characteristics and use behavior variables of persons who smoked exclusively. Regression coefficients, within- and between-person variance, and intra-class correlation coefficients were compared to biomarker smoking-nonsmoking population mean ratios and biological half-lives. RESULTS: Most biomarkers were similarly associated with sex, age, race/ethnicity, and product use behavior. The biomarkers with larger smoking-nonsmoking population mean ratios had greater regression coefficients related to recency of exposure. For VOC and alkaloid metabolites, longer biological half-life was associated with lower within-person variance. For each chemical class studied, there were biomarkers that demonstrated good intra-class correlation coefficients. CONCLUSIONS: For most of the biomarkers of exposure reported in the PATH Study, for people who smoke cigarettes exclusively, associations are similar between urinary biomarkers of exposure and demographic and use behavior covariates. Biomarkers of exposure within-subject consistency is likely associated with non-tobacco sources of exposure and biological half-life. IMPACT: Biomarkers measured in the PATH Study provide consistent sample-to-sample measures from which to investigate the association of adverse health outcomes with the characteristics of cigarettes and their use. |
Blood cadmium, lead, manganese, mercury, and selenium levels in American Indian populations: The Strong Heart Study
Li Z , Lewin M , Ruiz P , Nigra AE , Henderson N , Jarrett JM , Ward C , Zhu J , Umans JG , O'Leary M , Zhang Y , Ragin-Wilson A , Navas-Acien A . Environ Res 2022 215 114101 BACKGROUND: Many American Indian (AI) communities are in areas affected by environmental contamination, such as toxic metals. However, studies assessing exposures in AI communities are limited. We measured blood metals in AI communities to assess historical exposure and identify participant characteristics associated with these levels in the Strong Heart Study (SHS) cohort. METHOD: Archived blood specimens collected from 2014 participants (all participants were 50 years of age and older) in Arizona, Oklahoma, and North and South Dakota during SHS Phase-III (1998-1999) were analyzed for cadmium, lead, manganese, mercury, and selenium using inductively coupled plasma triple quadrupole mass spectrometry. We conducted descriptive analyses for the entire cohort and stratified by selected subgroups, including selected demographics, health behaviors, income, waist circumference, and body mass index. Bivariate associations were conducted to examine associations between blood metal levels and selected socio-demographic and behavioral covariates. Finally, multivariate regression models were used to assess the best model fit that predicted blood metal levels. FINDINGS: All elements were detected in 100% of study participants, with the exception of mercury (detected in 73% of participants). The SHS population had higher levels of blood cadmium and manganese than the general U.S. population 50 years and older. The blood mercury median of the SHS population was at about 30% of the U.S. reference population, potentially due to low fish consumption. Participants in North and South Dakota had the highest blood cadmium, lead, manganese, and selenium, and the lowest total mercury levels, even after adjusting for covariates. In addition, each of the blood metals was associated with selected demographic, behavioral, income, and/or weight-related factors in multivariate models. These findings will help guide the tribes to develop education, outreach, and strategies to reduce harmful exposures and increase beneficial nutrient intake in these AI communities. |
The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis
Walker TM , Fowler PW , Knaggs J , Hunt M , Peto TE , Walker AS , Crook DW , Walker TM , Miotto P , Cirillo DM , Kser CU , Knaggs J , Iqbal Z , Hunt M , Chindelevitch L , Farhat MR , Comas I , Comas I , Posey J , Omar SV , Peto TE , Walker AS , Crook DW , Suresh A , Uplekar S , Laurent S , Colman RE , Rodwell TC , Nathanson CM , Zignol M , Ismail N , Rodwell TC , Walker AS , Steyn AJC , Lalvani A , Baulard A , Christoffels A , Mendoza-Ticona A , Trovato A , Skrahina A , Lachapelle AS , Brankin A , Piatek A , GibertoniCruz A , Koch A , Cabibbe AM , Spitaleri A , Brandao AP , Chaiprasert A , Suresh A , Barbova A , VanRie A , Ghodousi A , Bainomugisa A , Mandal A , Roohi A , Javid B , Zhu B , Letcher B , Rodrigues C , Nimmo C , Nathanson CM , Duncan C , Coulter C , Utpatel C , Liu C , Grazian C , Kong C , Kser CU , Wilson DJ , Cirillo DM , Matias D , Jorgensen D , Zimenkov D , Chetty D , Moore DA , Clifton DA , Crook DW , vanSoolingen D , Liu D , Kohlerschmidt D , Barreira D , Ngcamu D , SantosLazaro ED , Kelly E , Borroni E , Roycroft E , Andre E , Bttger EC , Robinson E , Menardo F , Mendes FF , Jamieson FB , Coll F , Gao GF , Kasule GW , Rossolini GM , Rodger G , Smith EG , Meintjes G , Thwaites G , Hoffmann H , Albert H , Cox H , Laurenson IF , Comas I , Arandjelovic I , Barilar I , Robledo J , Millard J , Johnston J , Posey J , Andrews JR , Knaggs J , Gardy J , Guthrie J , Taylor J , Werngren J , Metcalfe J , Coronel J , Shea J , Carter J , Pinhata JM , Kus JV , Todt K , Holt K , Nilgiriwala KS , Ghisi KT , Malone KM , Faksri K , Musser KA , Joseph L , Rigouts L , Chindelevitch L , Jarrett L , Grandjean L , Ferrazoli L , Rodrigues M , Farhat M , Schito M , Fitzgibbon MM , Loemb MM , Wijkander M , Ballif M , Rabodoarivelo MS , Mihalic M , Wilcox M , Hunt M , Zignol M , Merker M , Egger M , O'Donnell M , Caws M , Wu MH , Whitfield MG , Inouye M , Mansj M , DangThi MH , Joloba M , Kamal SM , Okozi N , Ismail N , Mistry N , Hoang NN , Rakotosamimanana N , Paton NI , Rancoita PMV , Miotto P , Lapierre P , Hall PJ , Tang P , Claxton P , Wintringer P , Keller PM , Thai PVK , Fowler PW , Supply P , Srilohasin P , Suriyaphol P , Rathod P , Kambli P , Groenheit R , Colman RE , Ong RTH , Warren RM , Wilkinson RJ , Diel R , Oliveira RS , Khot R , Jou R , Tahseen S , Laurent S , Gharbia S , Kouchaki S , Shah S , Plesnik S , Earle SG , Dunstan S , Hoosdally SJ , Mitarai S , Gagneux S , Omar SV , Yao SY , GrandjeanLapierre S , Battaglia S , Niemann S , Pandey S , Uplekar S , Halse TA , Cohen T , Cortes T , Prammananan T , Kohl TA , Thuong NTT , Teo TY , Peto TEA , Rodwell TC , William T , Walker TM , Rogers TR , Surve U , Mathys V , Furi V , Cook V , Vijay S , Escuyer V , Dreyer V , Sintchenko V , Saphonn V , Solano W , Lin WH , vanGemert W , He W , Yang Y , Zhao Y , Qin Y , Xiao YX , Hasan Z , Iqbal Z , Puyen ZM , CryPticConsortium theSeq , Treat Consortium . Lancet Microbe 2022 3 (4) e265-e273 Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (73%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (07%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (914%), moxifloxacin (916%) and ethambutol (933%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation. 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license |
Development and validation of a biomonitoring method to measure As, Cr, and Ni in human urine samples by ICP-UCT-MS
Jones DR , Jarrett JM , Stukes D , Baer A , McMichael M , Wallon K , Xiao G , Jones RL . Int J Hyg Environ Health 2021 234 113713 We developed an inductively coupled plasma mass spectrometry (ICP-MS) method using Universal Cell Technology (UCT) with a PerkinElmer NexION ICP-MS, to measure arsenic (As), chromium (Cr), and nickel (Ni) in human urine samples. The advancements of the UCT allowed us to expand the calibration range to make the method applicable for both low concentrations of biomonitoring applications and high concentrations that may be observed from acute exposures and emergency response. Our method analyzes As and Ni in kinetic energy discrimination (KED) mode with helium (He) gas, and Cr in dynamic reaction cell (DRC) mode with ammonia (NH(3)) gas. The combination of these elements is challenging because a carbon source, ethanol (EtOH), is required for normalization of As ionization in urine samples, which creates a spectral overlap ((40)Ar(12)C(+)) on (52)Cr. This method additionally improved lab efficiency by combining elements from two of our previously published methods(Jarrett et al., 2007; Quarles et al., 2014) allowing us to measure Cr and Ni concentrations in urine samples collected as part of the National Health and Nutrition Examination Survey (NHANES) beginning with the 2017-2018 survey cycle. We present our rigorous validation of the method selectivity and accuracy using National Institute of Standards and Technology (NIST) Standard Reference Materials (SRM), precision using in-house prepared quality control materials, and a discussion of the use of a modified UCT, a BioUCell, to address an ion transmission phenomenon we observed on the NexION 300 platform when using higher elemental concentrations and high cell gas pressures. The rugged method detection limits, calculated from measurements in more than 60 runs, for As, Cr, and Ni are 0.23 μg L-1, 0.19 μg L-1, and 0.31 μg L-1, respectively. |
Exposure to nicotine and toxicants among dual users of tobacco cigarettes and e-cigarettes: Population Assessment of Tobacco and Health (PATH) Study, 2013-2014
Smith DM , Christensen C , van Bemmel D , Borek N , Ambrose B , Erives G , Niaura R , Edwards KC , Stanton CA , Blount BC , Wang L , Feng J , Jarrett JM , Ward CD , Hatsukami D , Hecht SS , Kimmel HL , Travers M , Hyland A , Goniewicz ML . Nicotine Tob Res 2021 23 (5) 790-797 INTRODUCTION: Concurrent use of tobacco cigarettes and e-cigarettes ("dual use") is common among tobacco users. Little is known about differences in demographics and toxicant exposure among subsets of dual users. AIMS AND METHODS: We analyzed data from adult dual users (current every/some day users of tobacco cigarettes and e-cigarettes, n = 792) included in the PATH Study Wave 1 (2013-2014) and provided urine samples. Samples were analyzed for biomarkers of exposure to nicotine and selected toxicants (tobacco-specific nitrosamine NNK [NNAL], lead, cadmium, naphthalene [2-naphthol], pyrene [1-hydroxypyrene], acrylonitrile [CYMA], acrolein [CEMA], and acrylamide [AAMA]). Subsets of dual users were compared on demographic, behavioral, and biomarker measures to exclusive cigarette smokers (n = 2411) and exclusive e-cigarette users (n = 247). RESULTS: Most dual users were predominant cigarette smokers (70%), followed by daily dual users (13%), non-daily concurrent dual users (10%), and predominant vapers (7%). Dual users who smoked daily showed significantly higher biomarker concentrations compared with those who did not smoke daily. Patterns of e-cigarette use had little effect on toxicant exposure. Dual users with high toxicant exposure were generally older, female, and smoked more cigarettes per day. Dual users who had low levels of biomarkers of exposure were generally younger, male, and smoked non-daily. CONCLUSIONS: In 2013-2014, most dual users smoked cigarettes daily and used e-cigarettes occasionally. Cigarette smoking appears to be the primary driver of toxicant exposure among dual users, with little-to-no effect of e-cigarette use on biomarker levels. Results reinforce the need for dual users to stop smoking tobacco cigarettes to reduce toxicant exposure. IMPLICATIONS: With considerable dual use of tobacco cigarettes and e-cigarettes in the United States, it is important to understand differences in toxicant exposure among subsets of dual users, and how these differences align with user demographics. Findings suggest most dual users smoke daily and use e-cigarettes intermittently. Low exposure to toxicants was most common among younger users, males, and intermittent smokers; high exposure to toxicants was most common among older users, females, and heavier cigarette smokers. Results underscore the heterogeneity occurring within dual users, and the need to quit smoking cigarettes completely in order to reduce toxicant exposure. |
Development of a pregnancy-specific referencematerial for thyroid biomarkers, vitaminD, and nutritional trace elements in serum
Boggs ASP , Kilpatrick LE , Burdette CQ , Tevis DS , Fultz ZA , Nelson MA , Jarrett JM , Kemp JV , Singh RJ , Grebe SKG , Wise SA , Kassim BL , Long SE . Clin Chem Lab Med 2020 59 (4) 671-679 Objectives Matrix differences among serum samples from non-pregnant and pregnant patients could bias measurements. Standard Reference Material 1949, Frozen Human Prenatal Serum, was developed to provide a quality assurance material for the measurement of hormones and nutritional elements throughout pregnancy. Methods Serum from non-pregnant women and women in each trimester were bottled into four levels based on pregnancy status and trimester. Liquid chromatography tandem mass spectrometry (LC-MS/MS) methods were developed and applied to the measurement of thyroid hormones, vitamin D metabolites, and vitamin D-binding protein (VDBP). Copper, selenium, and zinc measurements were conducted by inductively coupled plasma dynamic reaction cell MS. Thyroid stimulating hormone (TSH), thyroglobulin (Tg), and thyroglobulin antibody concentrations were analyzed using immunoassays and LC-MS/MS (Tg only). Results Certified values for thyroxine and triiodothyronine, reference values for vitamin D metabolites, VDBP, selenium, copper, and zinc, and information values for reverse triiodothyronine, TSH, Tg, and Tg antibodies were assigned. Significant differences in serum concentrations were evident for all analytes across the four levels (p≤0.003). TSH measurements were significantly different (p<0.0001) among research-only immunoassays. Tg concentrations were elevated in research-only immunoassays vs. Federal Drug Administration-approved automated immunoassay and LC-MS/MS. Presence of Tg antibodies increased differences between automated immunoassay and LC-MS/MS. Conclusions The analyte concentrations' changes consistent with the literature and the demonstration of matrix interferences in immunoassay Tg measurements indicate the functionality of this material by providing a relevant matrix-matched reference material for the different stages of pregnancy. |
Exposure to uranium and co-occurring metals among pregnant Navajo women
Hoover JH , Erdei E , Begay D , Gonzales M , Jarrett JM , Cheng PY , Lewis J . Environ Res 2020 190 109943 Navajo Nation residents are at risk for exposure to uranium and other co-occurring metals found in abandoned mine waste. The Navajo Birth Cohort Study (NBCS) was initiated in 2010 to address community concerns regarding the impact of chronic environmental exposure to metals on pregnancy and birth outcomes. The objectives of this paper were to 1) evaluate maternal urine concentrations of key metals at enrollment and delivery from a pregnancy cohort; and 2) compare the NBCS to the US general population by comparing representative summary statistical values. Pregnant Navajo women (N = 783, age range 14-45 years) were recruited from hospital facilities on the Navajo Nation during prenatal visits and urine samples were collected by trained staff in pre-screened containers. The U.S. Centers for Disease Control and Prevention (CDC), National Center for Environmental Health's (NCEH) Division of Laboratory Sciences (DLS) analyzed urine samples for metals. Creatinine-corrected urine concentrations of cadmium decreased between enrollment (1st or 2nd trimester) and delivery (3rd trimester) while urine uranium concentrations were not observed to change. Median and 95th percentile values of maternal NBCS urine concentrations of uranium, manganese, cadmium, and lead exceeded respective percentiles for National Health and Nutrition Evaluation Survey (NHANES) percentiles for women (ages 14-45 either pregnant or not pregnant.) Median NBCS maternal urine uranium concentrations were 2.67 (enrollment) and 2.8 (delivery) times greater than the NHANES median concentration, indicating that pregnant Navajo women are exposed to metal mixtures and have higher uranium exposure compared to NHANES data for women. This demonstrates support for community concerns about uranium exposure and suggests a need for additional analyses to evaluate the impact of maternal metal mixtures exposure on birth outcomes. |
Pregnancy outcomes among women receiving rVSVDelta-ZEBOV-GP Ebola vaccine during the Sierra Leone Trial to introduce a vaccine against Ebola
Legardy-Williams JK , Carter RJ , Goldstein ST , Jarrett OD , Szefer E , Fombah AE , Tinker SC , Samai M , Mahon BE . Emerg Infect Dis 2020 26 (3) 541-548 Little information exists regarding Ebola vaccine rVSVDeltaG-ZEBOV-GP and pregnancy. The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) randomized participants without blinding to immediate or deferred (18-24 weeks postenrollment) vaccination. Pregnancy was an exclusion criterion, but 84 women were inadvertently vaccinated in early pregnancy or became pregnant <60 days after vaccination or enrollment. Among immediate vaccinated women, 45% (14/31) reported pregnancy loss, compared with 33% (11/33) of unvaccinated women with contemporaneous pregnancies (relative risk 1.35, 95% CI 0.73-2.52). Pregnancy loss was similar among women with higher risk for vaccine viremia (conception before or <14 days after vaccination) (44% [4/9]) and women with lower risk (conception >15 days after vaccination) (45% [10/22]). No congenital anomalies were detected among 44 live-born infants examined. These data highlight the need for Ebola vaccination decisions to balance the possible risk for an adverse pregnancy outcome with the risk for Ebola exposure. |
Konzo outbreak in the Western Province of Zambia
Siddiqi OK , Kapina M , Kumar R , Ngomah Moraes A , Kabwe P , Mazaba ML , Hachaambwa L , Ng'uni NM , Chikoti PC , Morel-Espinosa M , Jarrett JM , Baggett HC , Chizema-Kawesha E . Neurology 2020 94 (14) e1495-e1501 OBJECTIVE: To identify the etiology of an outbreak of spastic paraparesis among women and children in the Western Province of Zambia suspected to be konzo. METHODS: We conducted an outbreak investigation of individuals from Mongu District, Western Province, Zambia, who previously developed lower extremity weakness. Cases were classified with the World Health Organization definition of konzo. Active case finding was conducted through door-to-door evaluation in affected villages and sensitization at local health clinics. Demographic, medical, and dietary history was used to identify common exposures in all cases. Urine and blood specimens were taken to evaluate for konzo and alternative etiologies. RESULTS: We identified 32 cases of konzo exclusively affecting children 6 to 14 years of age and predominantly females >14 years of age. Fourteen of 15 (93%) cases >/=15 years of age were female, 11 (73%) of whom were breastfeeding at the time of symptom onset. Cassava was the most commonly consumed food (median [range] 14 [4-21] times per week), while protein-rich foods were consumed <1 time per week for all cases. Of the 30 patients providing urine specimens, median thiocyanate level was 281 (interquartile range 149-522) mumol/L, and 73% of urine samples had thiocyanate levels >136 mumol/L, the 95th percentile of the US population in 2013 to 2014. CONCLUSION: This investigation revealed the first documented cases of konzo in Zambia, occurring in poor communities with diets high in cassava and low in protein, consistent with previous descriptions from neighboring countries. |
Characterization of trace elements exposure in pregnant women in the United States, NHANES 1999-2016
Watson CV , Lewin M , Ragin-Wilson A , Jones R , Jarrett JM , Wallon K , Ward C , Hilliard N , Irvin-Barnwell E . Environ Res 2020 183 109208 OBJECTIVE: The objective of the current study is to report on urine, blood and serum metal concentrations to characterize exposures to trace elements and micronutrient levels in both pregnant women and women of child-bearing age in the U.S. National Health and Nutrition Examination Survey (NHANES) years 1999-2016. METHODS: Urine and blood samples taken from NHANES participants were analyzed for thirteen urine metals, three blood metals, three serum metals, speciated mercury in blood and speciated arsenic in urine. Adjusted and unadjusted least squares geometric means and 95% confidence intervals were calculated for all participants among women aged 15-44 years. Changes in exposure levels over time were also examined. Serum cotinine levels were used to adjust for smoke exposure, as smoking is a source of metal exposure. RESULTS: Detection rates for four urine metals from the ATSDR Substance Priority List: arsenic, lead, mercury and cadmium were ~83-99% for both pregnant and non-pregnant women of child bearing age. A majority of metal concentrations were higher in pregnant women compared to non-pregnant women. Pregnant women had higher mean urine total arsenic, urine mercury, and urine lead; however, blood lead and mercury were higher in non-pregnant women. Blood lead, cadmium, mercury, as well as urine antimony, cadmium and lead in women of childbearing age decreased over time, while urine cobalt increased over time. CONCLUSIONS: Pregnant women in the US have been exposed to several trace metals, with observed concentrations for some trace elements decreasing since 1999. |
Biomarkers of exposure among adult smokeless tobacco users in the population assessment of Tobacco and Health Study (Wave 1, 2013-14)
Cheng YC , Reyes-Guzman CM , Christensen CH , Rostron BL , Edwards KC , Wang L , Feng J , Jarrett JM , Ward CD , Xia B , Kimmel HL , Conway K , Leggett C , Taylor K , Lawrence C , Niaura R , Travers MJ , Hyland A , Hecht SS , Hatsukami DK , Goniewicz ML , Borek N , Blount BC , van Bemmel DM . Cancer Epidemiol Biomarkers Prev 2020 29 (3) 659-667 BACKGROUND: Monitoring population-level toxicant exposures from smokeless tobacco (SLT) use is important for assessing population health risks due to product use. In this study, we assessed tobacco biomarkers of exposure (BOEs) among SLT users from the Wave 1 (2013-14) of the Population Assessment of Tobacco and Health (PATH) Study. METHODS: Urinary biospecimens were collected from adults aged 18 and older. Biomarkers of nicotine, tobacco-specific nitrosamines (TSNAs), polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), metals, and inorganic arsenic were analyzed and reported among exclusive current established SLT users in comparison to exclusive current established cigarette smokers, dual SLT and cigarette users, and never tobacco users. RESULTS: In general, SLT users (n=448) have significantly higher concentrations of biomarkers of exposure to nicotine, TSNAs and PAHs compared to never tobacco users; significant dose-response relationships between frequency of SLT use and biomarker concentrations were also reported among exclusive SLT daily users. Exclusive SLT daily users have higher geometric mean concentrations of total nicotine equivalent-2 (TNE2) and TSNAs than exclusive cigarette daily smokers. In contrast, geometric mean concentrations of PAHs and VOCs were substantially lower among exclusive SLT daily users than exclusive cigarette daily smokers. CONCLUSIONS: Our study produced a comprehensive assessment of SLT product use and 52 biomarkers of tobacco exposure. Compared to cigarette smokers, SLT users experience greater concentrations of some tobacco toxicants, including nicotine and TSNAs. IMPACT: Our data add information on the risk assessment of exposure to SLT-related toxicants. High levels of harmful constituents in SLT remain a health concern. |
Notes from the field: Methylmercury toxicity from a skin lightening cream obtained from Mexico - California, 2019
Mudan A , Copan L , Wang R , Pugh A , Lebin J , Barreau T , Jones RL , Ghosal S , Lee M , Albertson T , Jarrett JM , Lee J , Betting D , Ward CD , De Leon Salazar A , Smollin CG , Blanc PD . MMWR Morb Mortal Wkly Rep 2019 68 (50) 1166-1167 In July 2019, a Mexican-American woman aged 47 years in Sacramento, California, sought medical care for dysesthesias and weakness of her upper extremities. Over the ensuing 2 weeks of outpatient follow-up, her condition progressed to dysarthria, blurry vision, and gait unsteadiness, leading to hospital admission. While hospitalized, her condition declined rapidly to an agitated delirium. Two weeks into the hospitalization, screening blood and urine tests detected mercury concentrations exceeding the upper limit (UL) of quantification, indicative of abnormally high values of mercury (>160 μg/L [blood] and >80 μg/L [urine]). The hospital notified the California Poison Control System (CPCS) and the California Department of Public Health (CDPH). CPCS recommended oral dimercaptosuccinic acid, 10 mg/kg every 8 hours, which was administered via feeding tube. CDPH interviewed the patient’s family and learned that the patient was a long-term user of skin lightening creams obtained from Mexico (applied to the face twice daily for the past 7 years); the cream was analyzed and found to contain 12,000 ppm mercury. Mercury levels from the hospital specimens that initially implicated mercury were 2,620 μg/L blood mercury (reference population UL <1.81 μg/L)* and 110 μg/L urine mercury (UL <0.90 μg/L). A second blood specimen collected 11 days after the hospital initiation of ongoing dimercaptosuccinic acid chelation therapy detected 1,114 μg/L mercury. |
Knowledge, attitudes, and practices among veterinarians during an outbreak of canine leptospirosis-Maricopa County, Arizona, 2017
LaFerla Jenni M , Woodward P , Yaglom H , Levy C , Iverson SA , Kretschmer M , Jarrett N , Dooley E , Narang J , Venkat H . Prev Vet Med 2019 172 104779 Leptospirosis, caused by Leptospira spp., is a zoonotic bacterial disease important to both human and animal health. Six pathogenic serovars are currently known to commonly infect and cause disease in dogs in the United States. While canine leptospirosis infection is historically rare in Arizona (</=5 cases reported annually) (ADHS unpublished data) several clusters were reported in Maricopa County (MC) during February 2016-January 2017. Public health initiated an outbreak response and developed a knowledge, attitudes, and practices survey for veterinarians. The goals were to determine awareness and general attitudes about canine leptospirosis and to identify gaps in veterinarians' knowledge in treatment and prevention. We distributed a 40-question self-administered online survey to 1058 Arizona Veterinary Medical Association members, made available during February 9-May 15, 2017. We analyzed the results using Pearson's Chi-squared or Fisher's exact test; a P-value <0.05 was considered statistically significant. We analyzed 202 complete responses. Veterinarians from 10 (66%) of 15 Arizona counties were represented. MC practices were more likely to stock leptospirosis vaccine (80%) than other counties combined (58%) (P=0.004). The average composite knowledge score was 24.4 out of 38 (range 12-37, median 24); 49% of respondents demonstrated higher knowledge as defined by authors, largely in identification of leptospirosis risk factors (86%) and routes of exposure (73%). Fewer than half (45%) of respondents correctly identified the length of time bacteria can be shed in dogs' urine. Eighty-one percent of respondents demonstrated lower knowledge about clinical signs associated with leptospirosis; only 47% of respondents identified eight clinical signs commonly associated with leptospirosis. Sixty-one percent of MC respondents agreed that leptospirosis is an important canine disease in their geographic area, while only 40% of other county respondents agreed (P=0.03). Seventy percent of respondents identified diagnostic testing options. The majority correctly selected infection-control practices in line with recommendations from 2 national clinical guidelines. More respondents would recommend leptospirosis vaccination if dogs traveled or lived in rural areas (87-96%) than if dogs attended day care or were boarded (63%). We identified opportunities for education, including the local epidemiology of leptospirosis, transmission prevention strategies, vaccine safety, testing, clinical identification, and emerging risk factors. Our findings will help guide the design of educational materials for small animal veterinarians in Arizona regarding recommendations for prevention of animal and human leptospirosis infections; these efforts could also shift the culture of reporting companion animal diseases to improve future One Health collaborations. |
Vagococcus bubulae sp. nov., isolated from ground beef, and Vagococcus vulneris sp. nov., isolated from a human foot wound.
Shewmaker PL , Whitney AM , Gulvik CA , Humrighouse BW , Gartin J , Moura H , Barr JR , Moore ERB , Karlsson R , Pinto TCA , Teixeira LM . Int J Syst Evol Microbiol 2019 69 (8) 2268-2276 ![]() Two unusual catalase-negative, Gram-stain-positive, Vagococcus-like isolates that were referred to the CDC Streptococcus Laboratory for identification are described. Strain SS1994(T) was isolated from ground beef and strain SS1995(T) was isolated from a human foot wound. Comparative 16S rRNA gene sequence analysis of isolates SS1994(T) and SS1995(T) against Vagococcus type strain sequences supported their inclusion in the genus Vagococcus. Strain SS1994(T) showed high sequence similarity (>97.0 %) to the two most recently proposed species, Vagococcus martis (99.2 %) and Vagococcus teuberi (99.0 %) followed by Vagococcus penaei (98.8 %), strain SS1995(T) (98.6 %), Vagococcus carniphilus (98.0 %), Vagococcus acidifermentans (98.0 %) and Vagococcus fluvialis (97.9 %). The 16S rRNA gene sequence of strain SS1995(T) was most similar to V. penaei (99.1 %), followed by SS1994(T) (98.6 %), V. martis (98.4 %), V. teuberi (98.1 %), V. acidifermentans (97.8 %), and both V. carniphilus and V. fluvialis (97.5 %). A polyphasic taxonomic study using conventional biochemical and the rapid ID 32 STREP system, MALDI-TOF MS, cell fatty acid analysis, pairwise sequence comparisons of the 16S rRNA, rpoA, rpoB, pheS and groL genes, and comparative core and whole genome sequence analyses revealed that strains SS1994(T) and SS1995(T) were two novel Vagococcus species. The novel taxonomic status of the two isolates was confirmed with core genome phylogeny, average nucleotide identity <84 % and in silico DNA-DNA hybridization <28 % to any other Vagococcus species. The names Vagococcusbubulae SS1994(T)=(CCUG 70831(T)=LMG 30164(T)) and Vagococcusvulneris SS1995(T)=(CCUG 70832(T)=LMG 30165(T)) are proposed. |
LAMP: A CDC program to ensure the quality of blood-lead laboratory measurements
Caldwell KL , Cheng PY , Vance KA , Makhmudov A , Jarrett JM , Caudill SP , Ho DP , Jones RL . J Public Health Manag Pract 2019 25 S23-s30 CONTEXT: The Lead and Multielement Proficiency (LAMP) program is an external quality assurance program promoting high-quality blood-lead measurements. OBJECTIVES: To investigate the ability of US laboratories, participating in the Centers for Disease Control and Prevention (CDC) LAMP program to accurately measure blood-lead levels (BLL) 0.70 to 47.5 mug/dL using evaluation criteria of +/-2 mug/dL or 10%, whichever is greater. METHODS: The CDC distributes bovine blood specimens to participating laboratories 4 times per year. We evaluated participant performance over 5 challenges on samples with BLL between 0.70 and 47.5 mug/dL. The CDC sent 15 pooled samples (3 samples shipped in 5 rounds) to US laboratories. The LAMP laboratories used 3 primary technologies to analyze lead in blood: inductively coupled plasma mass spectrometry, graphite furnace atomic absorption spectroscopy, and LeadCare technologies based on anodic stripping voltammetry. Laboratories reported their BLL analytical results to the CDC. The LAMP uses these results to provide performance feedback to the laboratories. SETTING: The CDC sent blood samples to approximately 50 US laboratories for lead analysis. PARTICIPANTS: Of the approximately 200 laboratories enrolled in LAMP, 38 to 46 US laboratories provided data used in this report (January 2017 to March 2018). RESULTS: Laboratory precision ranged from 0.26 mug/dL for inductively coupled plasma mass spectrometry to 1.50 mug/dL for LeadCare instruments. All participating US LAMP laboratories reported accurate BLL for 89% of challenge samples, using the +/-2 mug/dL or 10% evaluation criteria. CONCLUSIONS: Laboratories participating in the CDC's LAMP program can accurately measure blood lead using the current Clinical Laboratory Improvement Amendments of 1988 guidance of +/-4 mug/dL or +/-10%, with a success rate of 96%. However, when we apply limits of +/-2 mug/dL or +/-10%, the success rate drops to 89%. When challenged with samples that have target values between 3 and 5 mug/dL, nearly 100% of reported results fall within +/-4 mug/dL, while 5% of the results fall outside of the acceptability criteria used by the CDC's LAMP program. As public health focuses on lower blood lead levels, laboratories must evaluate their ability to successfully meet these analytical challenges surrounding successfully measuring blood lead. In addition proposed CLIA guidelines (+/-2 mug/dL or 10%) would be achievable performance by a majority of US laboratories participating in the LAMP program. |
Waterpipe tobacco smoke: Characterization of toxicants and exposure biomarkers in a cross-sectional study of waterpipe employees
Kaplan B , Sussan T , Rule A , Moon K , Grau-Perez M , Olmedo P , Chen R , Carkoglu A , Levshin V , Wang L , Watson C , Blount B , Calafat AM , Jarrett J , Caldwell K , Wang Y , Breysse P , Strickland P , Cohen J , Biswal S , Navas-Acien A . Environ Int 2019 127 495-502 INTRODUCTION: Few studies have comprehensively characterized toxic chemicals related to waterpipe use and secondhand waterpipe exposure. This cross-sectional study investigated biomarkers of toxicants associated with waterpipe use and passive waterpipe exposure among employees at waterpipe venues. METHOD: We collected urine specimens from employees in waterpipe venues from Istanbul, Turkey and Moscow, Russia, and identified waterpipe and cigarette smoking status based on self-report. The final sample included 110 employees. Biomarkers of exposure to sixty chemicals (metals, volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), nicotine, and heterocyclic aromatic amines (HCAAs)) were quantified in the participants' urine. RESULTS: Participants who reported using waterpipe had higher urinary manganese (geometric mean ratio (GMR): 2.42, 95% confidence interval (CI): 1.16, 5.07) than never/former waterpipe or cigarette smokers. Being exposed to more hours of secondhand smoke from waterpipes was associated with higher concentrations of cobalt (GMR: 1.38, 95% CI: 1.10, 1.75). Participants involved in lighting waterpipes had higher urinary cobalt (GMR: 1.43, 95% CI: 1.10, 1.86), cesium (GMR: 1.21, 95% CI: 1.00, 1.48), molybdenum (GMR: 1.45, 95% CI: 1.08, 1.93), 1-hydroxypyrene (GMR: 1.36, 95% CI: 1.03, 1.80), and several VOC metabolites. CONCLUSION: Waterpipe tobacco users and nonsmoking employees of waterpipe venues had higher urinary concentrations of several toxic metals including manganese and cobalt as well as of VOCs, in a distinct signature compared to cigarette smoke. Employees involved in lighting waterpipes may have higher exposure to multiple toxic chemicals compared to other employees. |
Lead exposure during childhood and subsequent anthropometry through adolescence in girls
Deierlein AL , Teitelbaum SL , Windham GC , Pinney SM , Galvez MP , Caldwell KL , Jarrett JM , Gajek R , Kushi LH , Biro F , Wolff MS . Environ Int 2018 122 310-315 INTRODUCTION: Cross-sectional studies suggest that postnatal blood lead (PbB) concentrations are negatively associated with child growth. Few studies prospectively examined this association in populations with lower PbB concentrations. We investigated longitudinal associations of childhood PbB concentrations and subsequent anthropometric measurements in a multi-ethnic cohort of girls. METHODS: Data were from The Breast Cancer and the Environment Research Program at three sites in the United States (U.S.): New York City, Cincinnati, and San Francisco Bay Area. Girls were enrolled at ages 6-8years in 2004-2007. Girls with PbB concentrations collected at </=10years old (mean 7.8years, standard deviation (SD) 0.82) and anthropometry collected at >/=3 follow-up visits were included (n=683). The median PbB concentration was 0.99mug/d (10th percentile=0.59mug/dL and 90th percentile=2.00mug/dL) and the geometric mean was 1.03mug/dL (95% Confidence Interval (CI): 0.99, 1.06). For analyses, PbB concentrations were dichotomized as <1mug/dL (n=342) and >/=1mug/dL (n=341). Anthropometric measurements of height, body mass index (BMI), waist circumference (WC), and percent body fat (%BF) were collected at enrollment and follow-up visits through 2015. Linear mixed effects regression estimated how PbB concentrations related to changes in girls' measurements from ages 7-14years. RESULTS: At 7years, mean difference in height was -2.0cm (95% CI: -3.0, -1.0) for girls with >/=1mug/dL versus <1mug/dL PbB concentrations; differences persisted, but were attenuated, with age to -1.5cm (95% CI: -2.5, -0.4) at 14years. Mean differences for BMI, WC, and BF% at 7years between girls with >/=1mug/dL versus <1mug/dL PbB concentrations were -0.7kg/m(2) (95% CI: -1.2, -0.2), -2.2cm (95% CI: -3.8, -0.6), and -1.8% (95% CI: -3.2, -0.4), respectively. Overall, these differences generally persisted with advancing age and at 14years, differences were -0.8kg/m(2) (95% CI: -1.5, -0.02), -2.9cm (95% CI: -4.8, -0.9), and -1.7% (95% CI: -3.1, -0.4) for BMI, WC, and BF%, respectively. CONCLUSIONS: These findings suggest that higher concentrations of PbB during childhood, even though relatively low by screening standards, may be inversely associated with anthropometric measurements in girls. |
Availability and use of contraceptive implants in Jamaica: Results of a review of medical records and a survey of reproductive healthcare providers in six public health centres
Chevalier MS , King CC , Jarrett S , Sutherland S , Hill SM , Kourtis AP . West Indian Med J 2018 67 (2) 114-121 Objective: The prevalence of sub-dermal contraceptive implant use in Jamaica is low, despite growing international acceptance of long-acting reversible contraception. This study assessed the availability, effectiveness, side-effects and utilization of sub-dermal contraceptive implants and described the characteristics of users over a one-year period. Methods: We reviewed the medical records of women aged 15-45 years who utilized contraceptive implant-related services at any of the six included public health centres in Jamaica during 2013, and surveyed 20 available reproductive healthcare providers. Results: In 2013, 738 women attended a Jamaican public health centre for contraceptive implant services: 493 (66.8%) for insertion, 202 (27.4%) for removal and 53 (7.2%) for follow- up visits (10 women had the same implant inserted and removed in 2013). The women's median age was 26.0 years, 24.3% were <= 18 years, and 85.9% had >= 1 child. Most women (68.5%) did not have documented side-effects; irregular bleeding, the most commonly documented side-effect, was recorded for 24%. Of the 493 women who had implants inserted, three (0.6%) were identified to be pregnant within three months of insertion. Among the 202 women who had implants removed, 11 (5.4%) experienced complications with removal. Reproductive healthcare providers highlighted the need for an expansion of contraceptive implant availability and provider training. Conclusion: Sub-dermal implants have few insertion complications and side-effects and are effective, but were underutilized in Jamaica. Increased implant availability and enhanced reproductive healthcare provider training may improve implant utilization and reduce unintended pregnancy rates in Jamaica. |
Assessing the stability of Cd, Mn, Pb, Se, and total Hg in whole human blood by ICP-DRC-MS as a function of temperature and time
Tevis DS , Jarrett JM , Jones DR , Cheng PY , Franklin M , Mullinex N , Caldwell KL , Jones RL . Clin Chim Acta 2018 485 1-6 BACKGROUND: Comprehensive information on the effect of time and temperature storage on the measurement of elements in human, whole blood (WB) by inductively coupled plasma-dynamic reaction cell-mass spectrometry (ICP-DRC-MS) is lacking, particularly for Mn and Se. METHODS: Human WB was spiked at 3 concentration levels, dispensed, and then stored at 5 different temperatures: -70 degrees C, -20 degrees C, 4 degrees C, 23 degrees C, and 37 degrees C. At 3 and 5weeks, and at 2, 4, 6, 8, 10, 12, 36months, samples were analyzed for Pb, Cd, Mn, Se and total Hg, using ICP-DRC-MS. We used a multiple linear regression model including time and temperature as covariates to fit the data with the measurement value as the outcome. We used an equivalence test using ratios to determine if results from the test storage conditions, warmer temperature and longer time, were comparable to the reference storage condition of 3weeks storage time at -70 degrees C. RESULTS: Model estimates for all elements in human WB samples stored in polypropylene cryovials at -70 degrees C were equivalent to estimates from samples stored at 37 degrees C for up to 2months, 23 degrees C up to 10months, and -20 degrees C and 4 degrees C for up to 36months. Model estimates for samples stored for 3weeks at -70 degrees C were equivalent to estimates from samples stored for 2months at -20 degrees C, 4 degrees C, 23 degrees C and 37 degrees C; 10months at -20 degrees C, 4 degrees C, and 23 degrees C; and 36months at -20 degrees C and 4 degrees C. This equivalence was true for all elements and pools except for the low concentration blood pool for Cd. CONCLUSIONS: Storage temperatures of -20 degrees C and 4 degrees C are equivalent to -70 degrees C for stability of Cd, Mn, Pb, Se, and Hg in human whole blood for at least 36months when blood is stored in sealed polypropylene vials. Increasing the sample storage temperature from -70 degrees C to -20 degrees C or 4 degrees C can lead to large energy savings. The best analytical results are obtained when storage time at higher temperature conditions (e.g. 23 degrees C and 37 degrees C) is minimized because recovery of Se and Hg is reduced. Blood samples stored in polypropylene vials also lose volume over time and develop clots at higher temperature conditions (e.g., 23 degrees C and 37 degrees C), making them unacceptable for elemental testing after 10months and 2months, respectively. |
Health conditions in an adult population in Sierra Leone: Data reported from the Sierra Leone Trial to Introduce a Vaccine Against Ebola (STRIVE)
Fombah AE , Goldstein ST , Jarrett OD , Jalloh MI , El-Khorazaty J , Lisk DR , Legardy-Williams J , Pratt DA , George PM , Russell JBW , Schrag SJ , Dawson P , Deen GF , Carr W , Lindblad R , James F , Bah MM , Yillia JF , Sandy JD , Turay PE , Conteh MA , Slutsker L , Mahon BE , Samai M , Seward JF . J Infect Dis 2018 217 S75-s80 Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. |
Monitoring serious adverse events in the Sierra Leone Trial to Introduce a Vaccine Against Ebola
Jarrett OD , Seward JF , Fombah AE , Lindblad R , Jalloh MI , El-Khorazaty J , Dawson P , Burton D , Zucker J , Carr W , Bah MM , Deen GF , George PM , James F , Lisk DR , Pratt D , Russell JBW , Sandy JD , Turay P , Hamel MJ , Schrag SJ , Walker RE , Samai M , Goldstein ST . J Infect Dis 2018 217 S24-s32 Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. |
The Sierra Leone Trial to Introduce a Vaccine Against Ebola: An evaluation of rVSVG-ZEBOV-GP vaccine tolerability and safety during the West Africa Ebola outbreak
Samai M , Seward JF , Goldstein ST , Mahon BE , Lisk DR , Widdowson MA , Jalloh MI , Schrag SJ , Idriss A , Carter RJ , Dawson P , Kargbo SAS , Leigh B , Bawoh M , Legardy-Williams J , Deen G , Carr W , Callis A , Lindblad R , Russell JBW , Petrie CR , Fombah AE , Kargbo B , McDonald W , Jarrett OD , Walker RE , Gargiullo P , Bash-Taqi D , Gibson L , Fofanah AB , Schuchat A . J Infect Dis 2018 217 S6-s15 Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. |
Revisiting the taxonomy of the genus Elizabethkingia using whole-genome sequencing, optical mapping, and MALDI-TOF, along with proposal of three novel Elizabethkingia species: Elizabethkingia bruuniana sp. nov., Elizabethkingia ursingii sp. nov., and Elizabethkingia occulta sp. nov.
Nicholson AC , Gulvik CA , Whitney AM , Humrighouse BW , Graziano J , Emery B , Bell M , Loparev V , Juieng P , Gartin J , Bizet C , Clermont D , Criscuolo A , Brisse S , McQuiston JR . Antonie Van Leeuwenhoek 2017 111 (1) 55-72 ![]() ![]() The genus Elizabethkingia is genetically heterogeneous, and the phenotypic similarities between recognized species pose challenges in correct identification of clinically derived isolates. In addition to the type species Elizabethkingia meningoseptica, and more recently proposed Elizabethkingia miricola, Elizabethkingia anophelis and Elizabethkingia endophytica, four genomospecies have long been recognized. By comparing historic DNA-DNA hybridization results with whole genome sequences, optical maps, and MALDI-TOF mass spectra on a large and diverse set of strains, we propose a comprehensive taxonomic revision of this genus. Genomospecies 1 and 2 contain the type strains E. anophelis and E. miricola, respectively. Genomospecies 3 and 4 are herein proposed as novel species named as Elizabethkingia bruuniana sp. nov. (type strain, G0146T = DSM 2975T = CCUG 69503T = CIP 111191T) and Elizabethkingia ursingii sp. nov. (type strain, G4122T = DSM 2974T = CCUG 69496T = CIP 111192T), respectively. Finally, the new species Elizabethkingia occulta sp. nov. (type strain G4070T = DSM 2976T = CCUG 69505T = CIP 111193T), is proposed. |
Measurement challenges at low blood lead levels
Caldwell KL , Cheng PY , Jarrett JM , Makhmudov A , Vance K , Ward CD , Jones RL , Mortensen ME . Pediatrics 2017 140 (2) In 2012, the Centers for Disease Control and Prevention (CDC) adopted its Advisory Committee on Childhood Lead Poisoning Prevention recommendation to use a population-based reference value to identify children and environments associated with lead hazards. The current reference value of 5 mug/dL is calculated as the 97.5th percentile of the distribution of blood lead levels (BLLs) in children 1 to 5 years old from 2007 to 2010 NHANES data. We calculated and updated selected percentiles, including the 97.5th percentile, by using NHANES 2011 to 2014 blood lead data and examined demographic characteristics of children whose blood lead was ≥90th percentile value. The 97.5th percentile BLL of 3.48 microg/dL highlighted analytical laboratory and clinical interpretation challenges of blood lead measurements ≤5 mug/dL. Review of 5 years of results for target blood lead values <11 microg/dL for US clinical laboratories participating in the CDC's voluntary Lead and Multi-Element Proficiency quality assurance program showed 40% unable to quantify and reported a nondetectable result at a target blood lead value of 1.48 microg/dL, compared with 5.5% at a target BLL of 4.60 microg/dL. We describe actions taken at the CDC's Environmental Health Laboratory in the National Center for Environmental Health, which measures blood lead for NHANES, to improve analytical accuracy and precision and to reduce external lead contamination during blood collection and analysis. |
Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study
Shrivastava A , Kumar A , Thomas JD , Laserson KF , Bhushan G , Carter MD , Chhabra M , Mittal V , Khare S , Sejvar JJ , Dwivedi M , Isenberg SL , Johnson R , Pirkle JL , Sharer JD , Hall PL , Yadav R , Velayudhan A , Papanna M , Singh P , Somashekar D , Pradhan A , Goel K , Pandey R , Kumar M , Kumar S , Chakrabarti A , Sivaperumal P , Kumar AR , Schier JG , Chang A , Graham LA , Mathews TP , Johnson D , Valentin L , Caldwell KL , Jarrett JM , Harden LA , Takeoka GR , Tong S , Queen K , Paden C , Whitney A , Haberling DL , Singh R , Singh RS , Earhart KC , Dhariwal AC , Chauhan LS , Venkatesh S , Srikantiah P . Lancet Glob Health 2017 5 (4) e458-e466 BACKGROUND: Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country's largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. METHODS: In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). FINDINGS: Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9.6 [95% CI 3.6 - 24]) and absence of an evening meal (2.2 [1.2-4.3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7.8 [95% CI 3.3-18.8], without evening meal; OR 3.6 [1.1-11.1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12.4 mug/g to 152.0 mug/g and MCPG ranged from 44.9 mug/g to 220.0 mug/g. INTERPRETATION: Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. FUNDING: US Centers for Disease Control and Prevention. |
Analysis of whole human blood for Pb, Cd, Hg, Se, and Mn by ICP-DRC-MS for biomonitoring and acute exposures
Jones DR , Jarrett JM , Tevis DS , Franklin M , Mullinix NJ , Wallon KL , Derrick Quarles C Jr , Caldwell KL , Jones RL . Talanta 2017 162 114-122 We improved our inductively coupled plasma mass spectrometry (ICP-MS) whole blood method [1] for determination of lead (Pb), cadmium (Cd), and mercury (Hg) by including manganese (Mn) and selenium (Se), and expanding the calibration range of all analytes. The method is validated on a PerkinElmer (PE) ELAN® DRC II ICP-MS (ICP-DRC-MS) and uses the Dynamic Reaction Cell (DRC) technology to attenuate interfering background ion signals via ion-molecule reactions. Methane gas (CH4) eliminates background signal from 40Ar2 + to permit determination of 80Se+, and oxygen gas (O2) eliminates several polyatomic interferences (e.g. 40Ar15N+, 54Fe1H+) on 55Mn+. Hg sensitivity in DRC mode is a factor of two higher than vented mode when measured under the same DRC conditions as Mn due to collisional focusing of the ion beam. To compensate for the expanded method's longer analysis time (due to DRC mode pause delays), we implemented an SC4-FAST autosampler (ESI Scientific, Omaha, NE), which vacuum loads the sample onto a loop, to keep the sample-to-sample measurement time to less than 5 min, allowing for preparation and analysis of 60 samples in an 8-h work shift. The longer analysis time also resulted in faster breakdown of the hydrocarbon oil in the interface roughing pump. The replacement of the standard roughing pump with a pump using a fluorinated lubricant, Fomblin®, extended the time between pump maintenance. We optimized the diluent and rinse solution components to reduce carryover from high concentration samples and prevent the formation of precipitates. We performed a robust calculation to determine the following limits of detection (LOD) in whole blood: 0.07 µg dL−1 for Pb, 0.10 µg L−1 for Cd, 0.28 μg L−1 for Hg, 0.99 µg L−1 for Mn, and 24.5 µg L−1 for Se. © 2016 |
Complete Genome Sequences of Four Strains from the 2015-2016 Elizabethkingia anophelis Outbreak.
Nicholson AC , Whitney AM , Emery BD , Bell ME , Gartin JT , Humrighouse BW , Loparev VN , Batra D , Sheth M , Rowe LA , Juieng P , Knipe K , Gulvik C , McQuiston JR . Genome Announc 2016 4 (3) ![]() The complete circularized genome sequences of selected specimens from the largest known Elizabethkingia anophelis outbreak to date are described here. Genomic rearrangements observed among the outbreak strains are discussed. |
Cord blood methylmercury and fetal growth outcomes in Baltimore newborns: Potential confounding and effect modification by omega-3 fatty acids, selenium, and sex
Wells EM , Herbstman JB , Lin YH , Jarrett J , Verdon CP , Ward C , Caldwell KL , Hibbeln JR , Witter FR , Halden RU , Goldman LR . Environ Health Perspect 2016 124 (3) 373-9 BACKGROUND: Methylmercury (MeHg) may affect fetal growth; however, prior research often lacked assessment of mercury speciation, confounders, and interactions. OBJECTIVE: Our objective was to assess the relationship between MeHg and fetal growth as well as the potential for confounding or interaction of this relationship from speciated mercury, fatty acids, selenium, and sex. METHODS: This cross-sectional study includes 271 singletons born in Baltimore, Maryland, 2004-2005. Umbilical cord blood was analyzed for speciated mercury, serum omega-3 highly unsaturated fatty acids (n-3 HUFAs), and selenium. Multivariable linear regression models controlled for gestational age, birth weight, maternal age, parity, prepregnancy body mass index, smoking, hypertension, diabetes, selenium, n-3 HUFAs, and inorganic mercury (IHg). RESULTS: Geometric mean cord blood MeHg was 0.94 mug/L (95% CI: 0.84, 1.07). In adjusted models for ponderal index, betaln(MeHg) = -0.045 (g/cm3) x 100 (95% CI: -0.084, -0.005). There was no evidence of a MeHg x sex interaction with ponderal index. Contrastingly, there was evidence of a MeHg x n-3 HUFAs interaction with birth length [among low n-3 HUFAs, betaln(MeHg) = 0.40 cm, 95% CI: -0.02, 0.81; among high n-3 HUFAs, betaln(MeHg) = -0.15, 95% CI: -0.54, 0.25; p-interaction = 0.048] and head circumference [among low n-3 HUFAs, betaln(MeHg) = 0.01 cm, 95% CI: -0.27, 0.29; among high n-3 HUFAs, betaln(MeHg) = -0.37, 95% CI: -0.63, -0.10; p-interaction = 0.042]. The association of MeHg with birth weight and ponderal index was affected by n-3 HUFAs, selenium, and IHg. For birth weight, betaln(MeHg) without these variables was -16.8 g (95% CI: -75.0, 41.3) versus -29.7 (95% CI: -93.9, 34.6) with all covariates. Corresponding values for ponderal index were -0.030 (g/cm3) x 100 (95% CI: -0.065, 0.005) and -0.045 (95% CI: -0.084, -0005). CONCLUSION: We observed an association of increased MeHg with decreased ponderal index. There is evidence for interaction between MeHg and n-3 HUFAs; infants with higher MeHg and n-3 HUFAs had lower birth length and head circumference. These results should be verified with additional studies. |
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