Prevalence and measurement of dental caries in young children
Dye BA , Hsu KL , Afful J . Pediatr Dent 2015 37 (3) 200-16 PURPOSE: Dental caries in preschool children was historically considered to have a unique and more intense pattern of decay and was known by a variety of terms. In 1999, the term early childhood caries (ECC), along with a classification system, was proposed to facilitate epidemiologic research of dental caries in young children. The purpose of this study was to assess the impact of those early childhood caries recommendations on the prevalence and measurement of caries in preschool children. METHODS: A systematic search of the MEDLINE database was performed. Key search words included: ECC, dental decay, dental caries, carious dentin, baby bottle tooth decay, nursing caries, maxillary anterior caries, and labial caries. English language studies and studies on more than 100 children younger than six years old were eligible for selection. National Health and Nutrition Examination Survey data collected from 1988 to 1994, 1999 to 2004, and 2011 to 2012 were used to assess ECC prevalence using different operational definitions. RESULTS: There were 87 articles selected for this review. The term ECC was used in 55 percent of the selected articles as the primary outcome measure. The majority of studies used a cross-section study design, but diagnostic criteria varied greatly. Caries experience in young children may be shifting away from majority of untreated surfaces to a majority of restored surfaces. Little difference was observed by dental surface type in the distribution of decayed and filled surfaces in primary teeth. CONCLUSIONS: Although the term early childhood caries is widely used, varied use of diagnostic criteria and operational definitions continue to limit comparability across studies. Emerging changes in the proportion of decayed and filled surfaces in the United States also raises questions regarding the ECC case definition limiting our ability to understand the epidemiology of dental caries in preschool children. |
Gallbladder cancer incidence and mortality, United States 1999-2011
Henley SJ , Weir HK , Jim MA , Watson M , Richardson LC . Cancer Epidemiol Biomarkers Prev 2015 24 (9) 1319-26 BACKGROUND: Gallbladder cancer is a rare cancer with unusual distribution, and few population-based estimates for the United States have been published. METHODS: Using population-based cancer incidence and mortality data, we examined U.S. gallbladder cancer incidence and death rates for 2007-2011 and trends for 1999-2011. RESULTS: During 2007-2011, approximately 3,700 persons were diagnosed with primary gallbladder cancer (rate = 1.13 cases per 100,000) and 2,000 died from the disease (rate = 0.62 deaths per 100,000) each year in the United States. Two-thirds of gallbladder cancer cases and deaths occurred among women. Gallbladder cancer incidence and death rates were three times higher among American Indian and Alaska Native persons than non-Hispanic white persons. By state, gallbladder cancer incidence and death rates ranged by about two-fold. During 1999-2011 gallbladder cancer incidence rates decreased among women but remained level among men; death rates declined among women but stabilized among men after declining from 1999-2006. Gallbladder cancer incidence rates increased in some subgroups, notably among black persons, those aged <45 years and for endocrine tumors. CONCLUSIONS: Data from U.S. population-based cancer registries confirm that gallbladder cancer incidence and death rates are higher among women than men, highest among American Indian and Alaska Native persons, and differ by region. While overall incidence and death rates decreased during 1999-2011, incidence rates increased among some small subgroups. IMPACT: Surveillance of gallbladder cancer incidence and mortality, particularly to monitor increases in subgroups, may provide clues to etiology and stimulate further research. |
The role of heterogeneity in contact timing and duration in network models of influenza spread in schools
Toth DJ , Leecaster M , Pettey WB , Gundlapalli AV , Gao H , Rainey JJ , Uzicanin A , Samore MH . J R Soc Interface 2015 12 (108) 20150279 Influenza poses a significant health threat to children, and schools may play a critical role in community outbreaks. Mathematical outbreak models require assumptions about contact rates and patterns among students, but the level of temporal granularity required to produce reliable results is unclear. We collected objective contact data from students aged 5-14 at an elementary school and middle school in the state of Utah, USA, and paired those data with a novel, data-based model of influenza transmission in schools. Our simulations produced within-school transmission averages consistent with published estimates. We compared simulated outbreaks over the full resolution dynamic network with simulations on networks with averaged representations of contact timing and duration. For both schools, averaging the timing of contacts over one or two school days caused average outbreak sizes to increase by 1-8%. Averaging both contact timing and pairwise contact durations caused average outbreak sizes to increase by 10% at the middle school and 72% at the elementary school. Averaging contact durations separately across within-class and between-class contacts reduced the increase for the elementary school to 5%. Thus, the effect of ignoring details about contact timing and duration in school contact networks on outbreak size modelling can vary across different schools. |
Rotavirus-specific and overall diarrhea mortality in Chinese children younger than 5 years; 2003 to 2012
Zhang J , Duan Z , Payne DC , Yen C , Pan X , Chang Z , Liu N , Ye J , Ren X , Tate JE , Jiang B , Parashar UD . Pediatr Infect Dis J 2015 34 (10) e233-7 BACKGROUND: During the last decade, substantial declines in overall childhood mortality from diarrhea have been documented among Chinese children, but the last detailed assessment of rotavirus-specific mortality in China was conducted in 2002. To provide policy makers with up-to-date information, we examined rotavirus-related mortality in children >5 years of age in China during 2003-2012. METHODS: We obtained mortality rates for children <5 years of age from the Chinese Health Statistic Yearbook; these figures were multiplied by the proportion of deaths in this age group attributable to diarrhea from the Chinese Maternal and Child Mortality Surveillance (MCMS) to obtain estimates of diarrhea deaths in children <5 years of age. To estimate rotavirus deaths, diarrhea death estimates were multiplied by the detection rate of rotavirus in children hospitalized with diarrhea from the Viral Diarrhea Surveillance System (VDSS) in China and from peer-reviewed literature. FINDINGS: From 2003 to 2012, a total of 127,539 deaths from diarrhea were reported among Chinese children <5 years of age, of which an estimated 53,559 (42%) had illness attributable to rotavirus. Comparing 2003 to 2012, the annual number of deaths from rotavirus diarrhea decreased by 74% (from 10,531 to 2,791, respectively) and the mortality rate fell 74% (from 0.66 to 0.17 deaths per 1,000 live births, respectively). Ninety-three percent of all rotavirus deaths occurred in rural areas, where mortality rates (0.33 deaths per 1,000 live births in 2012) were 11 times greater than in urban areas (0.03 deaths per 1,000 live births in 2012). CONCLUSIONS: Rotavirus diarrhea mortality has substantially declined in the past decade in Chinese children. The vast majority of rotavirus deaths occurred in rural areas. There is potential value in using rotavirus vaccine interventions in rural areas to further reduce mortality from this disease. |
Sampling males who inject drugs in Haiphong, Vietnam: comparison of time-location and respondent-driven sampling methods
Tran HV , Le LV , Johnston LG , Nadol P , Van Do A , Tran HT , Nguyen TA . J Urban Health 2015 92 (4) 744-57 Accurate measurements of HIV prevalence and associated risk factors among hidden and high-risk groups are vital for program planning and implementation. However, only two sampling methods are purported to provide representative estimates for populations without sampling frames: time-location sampling (TLS) and respondent-driven sampling (RDS). Each method is subject to potential biases and questionable reliability. In this paper, we evaluate surveys designed to estimate HIV prevalence and associated risk factors among people who inject drugs (PWID) sampled through TLS versus RDS. In 2012, males aged ≥16 years who reported injecting drugs in the previous month and living in Haiphong, Vietnam, were sampled using TLS or RDS. Data from each survey were analyzed to compare HIV prevalence, related risk factors, socio-demographic characteristics, refusal estimates, and time and expenditures for field implementation. TLS (n = 432) and RDS (n = 415) produced similarly high estimates for HIV prevalence. Significantly lower proportions of PWID sampled through RDS received methadone treatment or met an outreach worker. Refusal estimates were lower for TLS than for RDS. Total expenditures per sample collected and number of person-days of staff effort were higher for TLS than for RDS. Both survey methods were successful in recruiting a diverse sample of PWID in Haiphong. In Vietnam, surveys of PWID are conducted throughout the country; although the refusal estimate was calculated to be much higher for RDS than TLS, RDS in Haiphong appeared to sample PWID with less exposure to services and required fewer financial and staff resources compared with TLS. |
Uptake of testing for HIV and syphilis among men who have sex with men in Baltimore, Maryland: 2004-2011
Said MA , German D , Flynn C , Linton SL , Blythe D , Cooley LA , Balaji AB , Oster AM . AIDS Behav 2015 19 (11) 2036-43 Men who have sex with men (MSM) in Baltimore are at disproportionately high risk for HIV and syphilis infection. Testing and diagnosis are important first steps in receiving treatment and reducing transmission. We analyzed cross-sectional data collected in 2004-2005, 2008, and 2011 among MSM not reporting a previous positive HIV test (n = 1268) in Baltimore, Maryland as part of the National HIV Behavioral Surveillance System to determine the proportion of men tested for HIV and/or syphilis within the previous 12 months and examine the extent to which opportunities for testing were being missed in health care settings. Within the previous 12 months, 54 % of men had received an HIV test; 31 % had received a syphilis test; and only 23 % of men had received testing for both. Among 979 men who did not receive both tests, 72 % had seen a health care provider in the past year, suggesting missed testing opportunities. |
Using syndromic surveillance to investigate tattoo-related skin infections in New York City
Kotzen M , Sell J , Mathes RW , Dentinger C , Lee L , Schiff C , Weiss D . PLoS One 2015 10 (6) e0130468 In response to two isolated cases of Mycobacterium chelonae infections in tattoo recipients where tap water was used to dilute ink, the New York City (NYC) Department of Health and Mental Hygiene conducted an investigation using Emergency Department (ED) syndromic surveillance to assess whether an outbreak was occuring. ED visits with chief complaints containing the key word "tattoo" from November 1, 2012 to March 18, 2013 were selected for study. NYC laboratories were also contacted and asked to report skin or soft tissue cultures in tattoo recipients that were positive for non-tuberculosis mycobacterial infection (NTM). Thirty-one TREDV were identified and 14 (45%) were interviewed to determine if a NTM was the cause for the visit. One ED visit met the case definition and was referred to a dermatologist. This individual was negative for NTM. No tattoo-associated NTM cases were reported by NYC laboratories. ED syndromic surveillance was utilized to investigate a non-reportable condition for which no other data source existed. The results were reassuring that an outbreak of NTM in tattoo recipients was not occurring. In response to concerns about potential NTM infections, the department sent a letter to all licensed tattoo artists advising them not to dilute tattoo ink with tap water. |
Potential impact of co-infections and co-morbidities prevalent in Africa on influenza severity and frequency: a systematic review
Cohen AL , McMorrow M , Walaza S , Cohen C , Tempia S , Alexander-Scott M , Widdowson MA . PLoS One 2015 10 (6) e0128580 Infectious diseases and underlying medical conditions common to Africa may affect influenza frequency and severity. We conducted a systematic review of published studies on influenza and the following co-infections or co-morbidities that are prevalent in Africa: dengue, malaria, measles, meningococcus, Pneumocystis jirovecii pneumonia (PCP), hemoglobinopathies, and malnutrition. Articles were identified except for influenza and PCP. Very few studies were from Africa. Sickle cell disease, dengue, and measles co-infection were found to increase the severity of influenza disease, though this is based on few studies of dengue and measles and the measles study was of low quality. The frequency of influenza was increased among patients with sickle cell disease. Influenza infection increased the frequency of meningococcal disease. Studies on malaria and malnutrition found mixed results. Age-adjusted morbidity and mortality from influenza may be more common in Africa because infections and diseases common in the region lead to more severe outcomes and increase the influenza burden. However, gaps exist in our knowledge about these interactions. |
Eighteen years of respiratory syncytial virus surveillance: changes in seasonality and hospitalization rates in southwestern Alaska native children
Bruden DJ , Singleton R , Hawk CS , Bulkow LR , Bentley S , Anderson LJ , Herrmann L , Chikoyak L , Hennessy TW . Pediatr Infect Dis J 2015 34 (9) 945-50 BACKGROUND: Alaska Native (AN) infants from the Yukon-Kuskokwim Delta (YKD) experienced respiratory syncytial virus (RSV) hospitalization rates five times higher and an RSV season twice as long as the general US infant population. We describe trends in hospitalization rates and seasonality during 18 years of continuous RSV surveillance in this population and explore contributions of climate and sociodemographic factors. METHODS: We abstracted clinical and RSV test information from computerized medical records at YKD Regional Hospital and Alaska Native Medical Center from 1994-2012 to determine hospitalization rates and RSV season timing. Descriptive village and weather data were acquired through the US Census and Alaska Climate Research Center, University of Alaska, Fairbanks, respectively. RESULTS: During 1994-2012, YKD infant RSV hospitalization rates declined nearly 3-fold, from 177/1,000 infants/year to 65. RSV season onset shifted later, from mid-October to late December, contributing to a significantly decreased season duration, from 30 weeks to 11 weeks. In a multivariate analysis, children from villages with more crowded households and lacking plumbed water had higher rates of RSV hospitalizations (RR 1.17, p=0.0005, and RR 1.45, p=0.0003). No association of temperature or dew point was found with the timing or severity of RSV season. CONCLUSIONS: Although the RSV hospitalization rate decreased 3-fold, YKD infants still experience a hospitalization rate 3-fold higher than the general US infant population. Overcrowding and lack of plumbed water were associated with RSV hospitalization. Dramatic changes occurred in RSV seasonality, not explained by changes in climate. |
Excess mortality associated with influenza among tuberculosis deaths in South Africa, 1999-2009
Walaza S , Cohen C , Nanoo A , Cohen AL , McAnerney J , von Mollendorf C , Moyes J , Tempia S . PLoS One 2015 10 (6) e0129173 BACKGROUND: Published data on the interaction between influenza and pulmonary tuberculosis (PTB) are limited. We aimed to estimate the influenza-associated mortality among individuals with PTB in South Africa from 1999-2009. METHODS: We modelled the excess influenza-associated mortality by applying Poisson regression models to monthly PTB and non-tuberculosis respiratory deaths, using laboratory-confirmed influenza as a covariate. RESULTS: PTB deaths increased each winter, coinciding with influenza virus circulation. Among individuals of any age, mean annual influenza-associated PTB mortality rate was 164/100,000 person-years (n = 439). The rate of non-tuberculosis respiratory deaths was 27/100,000 (n = 1125) for HIV-infected and 5/100,000 (n = 2367) for HIV-uninfected individuals of all ages. Among individuals aged <65 years, influenza-associated PTB mortality risk was elevated compared to influenza-associated non-tuberculosis respiratory deaths in HIV-infected (relative risk (RR): 5.2; 95% CI: 4.6-5.9) and HIV-uninfected individuals (RR: 61.0; CI: 41.4-91.0). Among individuals aged ≥65 years, influenza-associated PTB mortality risk was elevated compared to influenza-associated non-tuberculosis respiratory deaths in HIV-uninfected individuals (RR: 13.0; 95% CI: 12.0-14.0). CONCLUSION: We observed an increased risk of influenza-associated mortality in persons with PTB compared to non-tuberculosis respiratory deaths. If confirmed in other settings, our findings may support recommendations for active inclusion of patients with TB for influenza vaccination and empiric influenza anti-viral treatment of patients with TB during influenza epidemics. |
Hispanic men in the United States: acculturation and recent sexual behaviors with female partners, 2006-2010
Haderxhanaj LT , Rhodes SD , Romaguera RA , Bloom FR , Leichliter JS . Am J Public Health 2015 105 (8) e1-e8 OBJECTIVES: We examined Hispanic men's recent risky and protective sexual behaviors with female partners by acculturation. METHODS: Using the 2006-2010 National Survey of Family Growth, we performed bivariate analyses to compare acculturation groups (Hispanic Spanish-speaking immigrants, Hispanic English-speaking immigrants, Hispanic US natives, and non-Hispanic White men) by demographics and recent sexual behaviors with women. Multivariable logistic regression models for sexual behaviors by acculturation group were adjusted for demographics. RESULTS: Compared with Hispanic Spanish-speaking immigrants, non-Hispanic White men were less likely to report exchange of money or drugs for sex (adjusted odds ratio [AOR] = 0.3; 95% confidence interval [CI] = 0.1, 0.9), but were also less likely to report condom use at last vaginal (AOR = 0.6; 95% CI = 0.4, 0.8) and anal sex (AOR = 0.4; 95% CI = 0.3, 0.7). Hispanic US natives were less likely to report condom use at last vaginal sex than were Spanish-speaking immigrants (AOR = 0.6; 95% CI = 0.4, 0.8). English- and Spanish-speaking immigrants did not differ in risky or protective sexual behaviors. CONCLUSIONS: Our findings suggest that targeted interventions focusing on unique sexual risks and sociodemographic differences by acculturation level, particularly nativity, may be helpful for preventing sexually transmitted infections. |
Impact of and response to increased tuberculosis prevalence among Syrian refugees compared with Jordanian tuberculosis prevalence: case study of a tuberculosis public health strategy
Cookson ST , Abaza H , Clarke KR , Burton A , Sabrah NA , Rumman KA , Odeh N , Naoum M . Confl Health 2015 9 18 INTRODUCTION: By the summer of 2014, the Syrian crisis resulted in a regional humanitarian emergency with 2.9 million refugees, including 608,000 in Jordan. These refugees access United Nations High Commissioner for Refugees (UNHCR)-sponsored clinics or Jordan Ministry of Health clinics, including tuberculosis diagnosis and treatment. Tuberculosis care in Syria has deteriorated with destroyed health infrastructure and drug supply chain. Syrian refugees may have undiagnosed tuberculosis; therefore, the UNHCR, the International Organization for Migration (IOM), the National Tuberculosis Program (NTP), and the Centers for Disease Control and Prevention developed the Public Health Strategy for Tuberculosis among Syrian Refugees in Jordan. This case study presents that strategy, its impact, and recommendations for other neighboring countries. CASE DESCRIPTION: UNHCR determined that World Health Organization (WHO) criteria for implementing a tuberculosis program in an emergency were met for the Syrian refugees in Jordan. Jordan NTP assessed their tuberculosis program and found that access to Syrian refugees was the one component of their program missing. Therefore, a strategy for tuberculosis control among Syrian refugees was developed. Since that development through work with IOM, UNHCR, and NTP, tuberculosis case detection among Syrian refugees is almost 40 % greater (74 cases/12 months or 1.01/100,000 monthly through June 2014 vs. 56 cases/16 months or 0.73/100,000 monthly through June 2013) using estimated population figures; more than two fold the 2012 Jordan tuberculosis incidence. Additionally, the WHO objective of curing ≥85 % of newly identified infectious tuberculosis cases was met among Syrian refugees. DISCUSSION AND EVALUATION: Tuberculosis (TB) rates among displaced persons are high, but increased detection is possible. High TB rates were found among Syrian refugees through active screening and will probably persist as the Syrian crisis continues. Active screening can detect tuberculosis early and reduce risk for transmission. However, this strategy needs sustainable funding to continue and all activities have not been realized. CONCLUSIONS: Initial assessment found that tuberculosis among Syrian refugees was at a high incidence rate. Through partnership, a cohesive Jordanian tuberculosis strategy was developed for Syrian refugees and it has potential to inform treatment and control efforts for other regional countries impacted by the Syrian crisis. |
Impact of intensive handwashing promotion on secondary household influenza-like illness in rural Bangladesh: findings from a randomized controlled trial
Ram PK , DiVita MA , Khatun EJannat K , Islam M , Krytus K , Cercone E , Sohel BM , Ahmed M , Rahman AM , Rahman M , Yu J , Brooks WA , Azziz-Baumgartner E , Fry AM , Luby SP . PLoS One 2015 10 (6) e0125200 RATIONALE: There is little evidence for the efficacy of handwashing for prevention of influenza transmission in resource-poor settings. We tested the impact of intensive handwashing promotion on household transmission of influenza-like illness and influenza in rural Bangladesh. METHODS: In 2009-10, we identified index case-patients with influenza-like illness (fever with cough or sore throat) who were the only symptomatic person in their household. Household compounds of index case-patients were randomized to control or intervention (soap and daily handwashing promotion). We conducted daily surveillance and collected oropharyngeal specimens. Secondary attack ratios (SAR) were calculated for influenza and ILI in each arm. Among controls, we investigated individual risk factors for ILI among household contacts of index case-patients. RESULTS: Among 377 index case-patients, the mean number of days between fever onset and study enrollment was 2.1 (SD 1.7) among the 184 controls and 2.6 (SD 2.9) among 193 intervention case-patients. Influenza infection was confirmed in 20% of controls and 12% of intervention index case-patients. The SAR for influenza-like illness among household contacts was 9.5% among intervention (158/1661) and 7.7% among control households (115/1498) (SAR ratio 1.24, 95% CI 0.92-1.65). The SAR ratio for influenza was 2.40 (95% CI 0.68-8.47). In the control arm, susceptible contacts <2 years old (RRadj 5.51, 95% CI 3.43-8.85), those living with an index case-patient enrolled ≤24 hours after symptom onset (RRadj 1.91, 95% CI 1.18-3.10), and those who reported multiple daily interactions with the index case-patient (RRadj 1.94, 95% CI 1.71-3.26) were at increased risk of influenza-like illness. DISCUSSION: Handwashing promotion initiated after illness onset in a household member did not protect against influenza-like illness or influenza. Behavior may not have changed rapidly enough to curb transmission between household members. A reactive approach to reduce household influenza transmission through handwashing promotion may be ineffective in the context of rural Bangladesh. TRIAL REGISTRATION: ClinicalTrials.gov NCT00880659. |
Bacterial enteric infections among older adults in the United States: Foodborne Diseases Active Surveillance Network, 1996-2012
Scallan E , Crim SM , Runkle A , Henao OL , Mahon BE , Hoekstra RM , Griffin PM . Foodborne Pathog Dis 2015 12 (6) 492-9 BACKGROUND: A growing segment of the population-adults aged ≥65 years-is more susceptible than younger adults to certain enteric (including foodborne) infections and experience more severe disease. MATERIALS AND METHODS: Using data on laboratory-confirmed infections from the Foodborne Diseases Active Surveillance Network (FoodNet), we describe trends in the incidence of Campylobacter spp., Escherichia coli O157, Listeria monocytogenes, and nontyphoidal Salmonella infections in adults aged ≥65 years over time and by age group and sex. We used data from FoodNet and other sources to estimate the total number of illnesses, hospitalizations, and deaths in the United States caused by these infections each year using a statistical model to adjust for underdiagnosis (taking into account medical care-seeking, stool sample submission, laboratory practices, and test sensitivity). RESULTS: From 1996 to 2012, 4 pathogens caused 21,405 laboratory-confirmed infections among older adults residing in the FoodNet surveillance area; 49.3% were hospitalized, and 2.6% died. The average annual rate of infection was highest for Salmonella (12.8/100,000) and Campylobacter (12.1/100,000). Salmonella and Listeria led as causes of death. Among older adults, rates of laboratory-confirmed infection and the percentage of patients who were hospitalized and who died generally increased with age. A notable exception was the rate of Campylobacter infections, which decreased with increasing age. Adjusting for underdiagnosis, we estimated that these pathogens caused about 226,000 illnesses ( approximately 600/100,000) annually among U.S. adults aged ≥65 years, resulting in approximately 9700 hospitalizations and approximately 500 deaths. CONCLUSIONS: Campylobacter, E. coli O157, Listeria, and Salmonella are major contributors to illness in older adults, highlighting the value of effective and targeted intervention. |
Repeatedly high polycyclic aromatic hydrocarbon exposure and cockroach sensitization among inner-city children
Jung KH , Lovinsky-Desir S , Perzanowski M , Liu X , Maher C , Gil E , Torrone D , Sjodin A , Li Z , Perera FP , Miller RL . Environ Res 2015 140 649-656 BACKGROUND: Exposures to traffic-related air pollutants including polycyclic aromatic hydrocarbons (PAH) have been associated with the development and exacerbation of asthma. However, there is limited evidence on whether these pollutants are associated with the development of cockroach sensitization, a strong risk factor for urban asthma. We hypothesized that repeatedly high PAH exposure during childhood would be associated with increased risk of new cockroach sensitization. METHODS: As part of the research being conducted by the Columbia Center for Children's Environmental Health (CCCEH) birth cohort study in New York, a spot urine sample was collected from children at age 5 years (2003-2008) and again at age 9-10 years (2008-2012; n=248) and analyzed for 10 PAH metabolites. Repeatedly high PAH (High-High) exposure was defined as measures above median for age 5 PAH metabolites at both time points. Child blood samples at age 5 and 9 years were analyzed for total, anti-cockroach, mouse, dust mite, cat and dog IgE. Relative risks (RR) were estimated with multivariable modified Poisson regression. RESULTS: Individual PAH metabolite levels, except for 1-naphthol (1-OH-NAP), increased by 10-60% from age 5 to age 9-10. The prevalence of cockroach sensitization increased from 17.6% (33/188) at age 5 to 33.0% (62/188) at 9 years (p=0.001). After controlling for potential covariates including cockroach sensitization at age 5 in regression analyses, positive associations were found between repeatedly high exposure (High-High) to 1-OH-NAP, 3-hydroxyphenanthrene (3-OH-PHEN), or 1-hydroxypyrene (1-OH-PYR) and cockroach sensitization at age 9 (p-values<0.05). Compared to Low-Low exposure, the relative risk (RR) [95% CI] with repeatedly high exposure was 1.83 [1.06-3.17] for 1-OH-NAP, 1.54 [1.06-2.23] for 3-OH-PHEN, and 1.59 [1.04-2.43] for 1-OH-PYR. CONCLUSIONS: Repeatedly high levels of urinary PAH metabolites during childhood may increase likelihood of sensitization to cockroach allergen in urban inner-city children at age 9 years. |
Polybrominated diphenyl ethers and thyroid cancer risk in the Prostate, Colorectal, Lung, and Ovarian Cancer Screening Trial cohort
Aschebrook-Kilfoy B , DellaValle CT , Purdue M , Kim C , Zhang Y , Sjodin A , Ward MH . Am J Epidemiol 2015 181 (11) 883-8 Polybrominated diphenyl ethers (PBDEs) alter thyroid hormone homeostasis, but their relationship with thyroid cancer is unknown. To investigate whether serum concentrations of PBDE were associated with thyroid cancer, we conducted a nested, case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a large multicenter clinical trial in the United States. Cases with thyroid cancer (n = 104) were recruited from 1992 to 2001 and diagnosed through 2009, and controls (n = 208) were individually matched (2:1) to cases by race, sex, birth date (within 1 year), center, and blood collection date (within 15 days). We used gas chromatography isotope dilution high-resolution mass spectrometry to measure 10 tri- to heptabrominated diphenyl eithers in serum samples. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression for lipid-adjusted PBDE levels detected in more than 50% of controls and for the sum of these BDEs ( summation operatorPBDEs). We observed no significant differences between cases and controls in lipid-adjusted concentrations of summation operatorPBDEs (for cases, median = 12.8 ng/g lipid (interquartile range, 6.2-42.1); for controls, median = 19.4 ng/g lipid (interquartile range, 7.6-50.2)) or for individual congeners. Increasing quartiles of summation operatorPBDEs and 4 BDE congeners were not associated with risk of thyroid cancer (for the fourth vs. first quartile of summation operatorPBDEs, adjusted odd ratio = 0.62, 95% confidence interval: 0.29, 1.30; P for trend = 0.56). Our study does not support an association between exposure to PBDEs and thyroid cancer. |
Considerations before establishing an environmental health registry
Antao VC , Muravov OI , Sapp J 2nd , Larson TC , Pallos LL , Sanchez ME , Williamson GD , Horton DK . Am J Public Health 2015 105 (8) e1-e8 Public health registries can provide valuable information when health consequences of environmental exposures are uncertain or will likely take long to develop. They can also aid research on diseases that may have environmental causes that are not completely well defined. We discuss factors to consider when deciding whether to create an environmental health registry. Those factors include public health significance, purpose and outcomes, duration and scope of data collection and availability of alternative data sources, timeliness, availability of funding and administrative capabilities, and whether the establishment of a registry can adequately address specific health concerns. We also discuss difficulties, limitations, and benefits of exposure and disease registries, based on the experience of the Agency for Toxic Substances and Disease Registry. |
A Novel Botulinum Toxin, Previously Reported as Serotype H, has a Hybrid Structure of Known Serotypes A and F that is Neutralized with Serotype A Antitoxin.
Maslanka SE , Luquez C , Dykes JK , Tepp WH , Pier CL , Pellett S , Raphael BH , Kalb SR , Barr JR , Rao A , Johnson EA . J Infect Dis 2015 213 (3) 379-85 Botulism is a potentially fatal paralytic disease caused by the action of botulinum neurotoxin (BoNT) on nerve cells. There are 7 known serotypes (A through G) of BoNT and up to 40 genetic variants. Clostridium botulinum strain IBCA10-7060 was recently reported to produce BoNT serotype B (BoNT/B) and a novel BoNT, designated by the authors as BoNT/H. The botulinum neurotoxin gene (bont) sequence of BoNT/H was analyzed against known related bont sequences. Genetic analysis suggested that BoNT/H has a hybrid-like structure containing regions of similarity to BoNT/A1 and /F5. This novel BoNT was serologically characterized by the mouse neutralization assay and a neuronal cell-based assay. The toxic effects of this hybrid-like BoNT were completely eliminated by existing serotype A antitoxin including those contained in multivalent therapeutic antitoxin products that are the mainstay for human botulism treatment. |
Phylodynamics of Enterovirus A71-Associated Hand, Foot and Mouth Disease in Viet Nam.
Geoghegan JL , Van Tan L , Kuhnert D , Halpin RA , Lin X , Simenauer A , Akopov A , Das SR , Stockwell TB , Shrivastava S , Ngoc NM , Uyen LT , Tuyen NT , Thanh TT , Hang VT , Qui PT , Hung NT , Khanh TH , Thinh LQ , Nhan LN , Van HM , Viet DC , Tuan HM , Viet HL , Hien TT , Chau NV , Thwaites G , Grenfell BT , Stadler T , Wentworth DE , Holmes EC , Van Doorn HR . J Virol 2015 89 (17) 8871-9 Enterovirus A71 (EV-A71) is a major cause of hand, foot and mouth disease (HFMD) and is particularly prevalent in parts of Southeast Asia, affecting thousands of children and infants each year. Revealing the evolutionary and epidemiological dynamics of EV-A71 through time and space is central to understanding its outbreak potential. We generated the full genome sequences of 200 EV-A71 strains sampled from various locations in Viet Nam between 2011-2013, and used these sequence data to determine the evolutionary history and phylodynamics of EV-A71 in Viet Nam, providing estimates of the effective reproduction number (Re) of the infection through time. In addition, we described the phylogeography of EV-A71 throughout Southeast Asia, documenting patterns of viral gene flow. Accordingly, our analysis reveals that a rapid genogroup switch from C4 to B5 likely took place during 2012 in Viet Nam. We show that the Re of subgenogroup C4 decreased during the time-frame of sampling, while that of B5 increased and remained >1 at the end of 2013, corresponding to a rise in B5 prevalence. Our study reveals that the subgenogroup B5 virus that emerged into Viet Nam is closely related to variants that were responsible for large epidemics in Malaysia and Taiwan and therefore extends our knowledge regarding its associated endemic area. Subgenogroup B5 evidently has the potential to cause more widespread outbreaks across Southeast Asia. IMPORTANCE: EV-A71 is one of many viruses that cause HFMD, a common syndrome that largely affects infants and children. HFMD usually causes only mild illness with no long-term consequences. Occasionally, however, severe infection may arise, especially in very young children, causing neurological complications and even death. EV-A71 is highly contagious and is associated with the most severe HFMD cases, with large and frequent epidemics of the virus recorded worldwide. Although major advances have been made in the development of a potential EV-A71 vaccine, there is no current prevention and little is known about the patterns and dynamics of EV-A71 spread. In this study we utilize full-length genome sequence data obtained from HFMD patients in Viet Nam, a geographical region where the disease has been endemic since 2003, to characterize the phylodynamics of this important emerging virus. |
Identification of Influenza A/PR/8/34 Donor Viruses Imparting High Hemagglutinin Yields to Candidate Vaccine Viruses in Eggs.
Johnson A , Chen LM , Winne E , Santana W , Metcalfe MG , Mateu-Petit G , Ridenour C , Hossain MJ , Villanueva J , Zaki SR , Williams TL , Cox NJ , Barr JR , Donis RO . PLoS One 2015 10 (6) e0128982 One of the important lessons learned from the 2009 H1N1 pandemic is that a high yield influenza vaccine virus is essential for efficient and timely production of pandemic vaccines in eggs. The current seasonal and pre-pandemic vaccine viruses are generated either by classical reassortment or reverse genetics. Both approaches utilize a high growth virus, generally A/Puerto Rico/8/1934 (PR8), as the donor of all or most of the internal genes, and the wild type virus recommended for inclusion in the vaccine to contribute the hemagglutinin (HA) and neuraminidase (NA) genes encoding the surface glycoproteins. As a result of extensive adaptation through sequential egg passaging, PR8 viruses with different gene sequences and high growth properties have been selected at different laboratories in past decades. The effect of these related but distinct internal PR8 genes on the growth of vaccine viruses in eggs has not been examined previously. Here, we use reverse genetics to analyze systematically the growth and HA antigen yield of reassortant viruses with 3 different PR8 backbones. A panel of 9 different HA/NA gene pairs in combination with each of the 3 different lineages of PR8 internal genes (27 reassortant viruses) was generated to evaluate their performance. Virus and HA yield assays showed that the PR8 internal genes influence HA yields in most subtypes. Although no single PR8 internal gene set outperformed the others in all candidate vaccine viruses, a combination of specific PR8 backbone with individual HA/NA pairs demonstrated improved HA yield and consequently the speed of vaccine production. These findings may be important both for production of seasonal vaccines and for a rapid global vaccine response during a pandemic. |
Prediction of complex human diseases from pathway-focused candidate markers by joint estimation of marker effects: case of chronic fatigue syndrome.
Bhattacharjee M , Rajeevan MS , Sillanpaa MJ . Hum Genomics 2015 9 (1) 8 BACKGROUND: The current practice of using only a few strongly associated genetic markers in regression models results in generally low power in prediction or accounting for heritability of complex human traits. PURPOSE: We illustrate here a Bayesian joint estimation of single nucleotide polymorphism (SNP) effects principle to improve prediction of phenotype status from pathway-focused sets of SNPs. Chronic fatigue syndrome (CFS), a complex disease of unknown etiology with no laboratory methods for diagnosis, was chosen to demonstrate the power of this Bayesian method. For CFS, such a genetic predictive model in combination with clinical evidence might lead to an earlier diagnosis than one based solely on clinical findings. METHODS: One of our goals is to model disease status using Bayesian statistics which perform variable selection and parameter estimation simultaneously and which can induce the sparseness and smoothness of the SNP effects. Smoothness of the SNP effects is obtained by explicit modeling of the covariance structure of the SNP effects. RESULTS: The Bayesian model achieved perfect goodness of fit when tested within the sampled data. Tenfold cross-validation resulted in 80 % accuracy, one of the best so far for CFS in comparison to previous prediction models. Model reduction aspects were investigated in a computationally feasible manner. Additionally, genetic variation estimates provided by the model identified specific genetic markers for their biological role in the disease pathophysiology. CONCLUSIONS: This proof-of-principle study provides a powerful approach combining Bayesian methods, SNPs representing multiple pathways and rigorous case ascertainment for accurate genetic risk prediction modeling of complex diseases like CFS and other chronic diseases. |
Sequence specificity for uridylylation of the viral peptide linked to the genome (VPg) of enteroviruses.
Schein CH , Ye M , Paul AV , Oberste MS , Chapman N , van der Heden van Noort GJ , Filippov DV , Choi K . Virology 2015 484 80-85 Enteroviruses (EV) uridylylate a peptide, VPg, as the first step in their replication. VPgpUpU, found free in infected cells, serves as the primer for RNA elongation. The abilities of four polymerases (3Dpol), from EV-species A-C, to uridylylate VPgs that varied by up to 60% of their residues were compared. Each 3Dpol was able to uridylylate all five VPgs using polyA RNA as template, while showing specificity for its own genome encoded peptide. All 3Dpol uridylylated a consensus VPg representing the physical chemical properties of 31 different VPgs. Thus the residues required for uridylylation and the enzymatic mechanism must be similar in diverse EV. As VPg-binding sites differ in co-crystal structures, the reaction is probably done by a second 3Dpol molecule. The conservation of polymerase residues whose mutation reduces uridylylation but not RNA elongation is compared. |
Bacterial factors associated with lethal outcome of enteropathogenic Escherichia coli infection: genomic case-control studies
Donnenberg MS , Hazen TH , Farag TH , Panchalingam S , Antonio M , Hossain A , Mandomando I , Ochieng JB , Ramamurthy T , Tamboura B , Zaidi A , Levine MM , Kotloff K , Rasko DA , Nataro JP . PLoS Negl Trop Dis 2015 9 (5) e0003791 BACKGROUND: Typical enteropathogenic Escherichia coli (tEPEC) strains were associated with mortality in the Global Enteric Multicenter Study (GEMS). Genetic differences in tEPEC strains could underlie some of the variability in clinical outcome. METHODS: We produced draft genome sequences of all available tEPEC strains from GEMS lethal infections (LIs) and of closely matched EPEC strains from GEMS subjects with non-lethal symptomatic infections (NSIs) and asymptomatic infections (AIs) to identify gene clusters (potential protein encoding sequences sharing ≥90% nucleotide sequence identity) associated with lethality. RESULTS: Among 14,412 gene clusters identified, the presence or absence of 392 was associated with clinical outcome. As expected, more gene clusters were associated with LI versus AI than LI versus NSI. The gene clusters more prevalent in strains from LI than those from NSI and AI included those encoding proteins involved in O-antigen biogenesis, while clusters encoding type 3 secretion effectors EspJ and OspB were among those more prevalent in strains from non-lethal infections. One gene cluster encoding a variant of an NleG ubiquitin ligase was associated with LI versus AI, while two other nleG clusters had the opposite association. Similar associations were found for two nleG gene clusters in an additional, larger sample of NSI and AI GEMS strains. CONCLUSIONS: Particular genes are associated with lethal tEPEC infections. Further study of these factors holds potential to unravel the mechanisms underlying severe disease and to prevent adverse outcomes. |
Healthcare laundry and textiles in the United States: review and commentary on contemporary infection prevention issues
Sehulster LM . Infect Control Hosp Epidemiol 2015 36 (9) 1-16 Healthcare professionals have questions about the infection prevention effectiveness of contemporary laundry processes for healthcare textiles (HCTs). Current industrial laundry processes achieve microbial reductions via physical, chemical, and thermal actions, all of which result in producing hygienically clean HCTs. European researchers have demonstrated that oxidative laundry additives have sufficient potency to meet US Environmental Protection Agency benchmarks for sanitizers and disinfectants. Outbreaks of infectious diseases associated with laundered HCTs are extremely rare; only 12 such outbreaks have been reported worldwide in the past 43 years. Root cause analyses have identified inadvertent exposure of clean HCTs to environmental contamination (including but not limited to exposure to dust in storage areas) or a process failure during laundering. To date, patient-to-patient transmission of infection has not been associated with hygienically clean HCTs laundered in accordance with industry process standards. Occupationally acquired infection involved mishandling of soiled HCTs and failure to use personal protective equipment properly. Laboratory studies of antimicrobial treatments for HCTs demonstrate a wide range of activity from 1 to 7 log10 reduction of pathogens under various experimental conditions. Clinical studies are needed to evaluate potential use of these treatments for infection prevention. Microbiological testing of clean HCTs for certification purposes is now available in the United States. Key features (eg, microbial sampling strategy, numbers of textiles sampled) and justification of the testing are discussed. |
Update on Vaccine-Derived Polioviruses - Worldwide, January 2014-March 2015.
Diop OM , Burns CC , Sutter RW , Wassilak SG , Kew OM . MMWR Morb Mortal Wkly Rep 2015 64 (23) 640-646 Since the World Health Assembly's 1988 resolution to eradicate poliomyelitis, one of the main tools of the World Health Organization (WHO) Global Polio Eradication Initiative (GPEI) has been the live, attenuated oral poliovirus vaccine (OPV). OPV might require several doses to induce immunity but provides long-term protection against paralytic disease. Through effective use of OPV, GPEI has brought polio to the threshold of eradication. Wild poliovirus type 2 (WPV2) was eliminated in 1999, WPV3 has not been detected since November 2012, and WPV1 circulation appears to be restricted to parts of Pakistan and Afghanistan. However, continued use of OPV carries two key risks. The first, vaccine-associated paralytic poliomyelitis (VAPP) has been recognized since the early 1960s. VAPP is a very rare event that occurs sporadically when an administered dose of OPV reverts to neurovirulence and causes paralysis in the vaccine recipient or a nonimmune contact. VAPP can occur among immunologically normal vaccine recipients and their contacts as well as among persons who have primary immunodeficiencies (PIDs) manifested by defects in antibody production; it is not associated with outbreaks. The second, the emergence of genetically divergent, neurovirulent vaccine-derived polioviruses (VDPVs) was recognized more recently. Circulating VDPVs (cVDPVs) resemble WPVs and, in areas with low OPV coverage, can cause polio outbreaks. Immunodeficiency-associated VDPVs (iVDPVs) can replicate and be excreted for years in some persons with PIDs; GPEI maintains a registry of iVDPV cases. Ambiguous VDPVs (aVDPVs) are isolates that cannot be classified definitively. This report updates previous surveillance summaries and describes VDPVs detected worldwide during January 2014-March 2015. Those include new cVDPV outbreaks in Madagascar and South Sudan, and sharply reduced type 2 cVDPV (cVDPV2) circulation in Nigeria and Pakistan during the latter half of 2014. Eight newly identified persons in six countries were found to excrete iVDPVs, and a patient in the United Kingdom was still excreting iVDPV2 in 2014 after more than 28 years. Ambiguous VDPVs were found among immunocompetent persons and environmental samples in 16 countries. Because the large majority of VDPV case-isolates are type 2, WHO has developed a plan for coordinated worldwide withdrawal of trivalent (types 1, 2, and 3) OPV (tOPV) and replacement with bivalent (types 1 and 3) OPV (bOPV) in April 2016, preceded by introduction of at least 1 dose of injectable inactivated poliovirus vaccine (IPV) into routine immunization schedules worldwide to maintain immunity to type 2 viruses. |
Substantial decline in hepatitis B virus infections following vaccine introduction in Tajikistan
Khetsuriani N , Tishkova F , Jabirov S , Wannemuehler K , Kamili S , Pirova Z , Mosina L , Gavrilin E , Ursu P , Drobeniuc J . Vaccine 2015 33 (32) 4019-24 BACKGROUND: Tajikistan, considered highly endemic area for hepatitis B virus (HBV) in a pre-vaccine era, introduced hepatitis B vaccine in 2002 and reported ≥80% coverage with three doses of hepatitis B vaccine (HepB3) since 2004. However, the impact of vaccine introduction has not been assessed. METHODS: We tested residual serum specimens from a 2010 national serosurvey for vaccine-preventable diseases in Tajikistan and assessed the prevalence of HBV infection across groups defined based on the birth cohorts' routine infant hepatitis B vaccination program implementation and HepB3 coverage achieved (≥80% versus <80%). Serosurvey participants were selected through stratified multi-stage cluster sampling among residents of all regions of Tajikistan aged 1-24 years. All specimens were tested for antibodies against HBV core antigen (anti-HBc) and those found positive were tested for HBV surface antigen (HBsAg). Seroprevalence and 95% confidence intervals were calculated and compared across subgroups using Satterthwaite-adjusted chi-square tests, accounting for the survey design and sampling weights. RESULTS: A total of 2188 samples were tested. Prevalence of HBV infection markers was lowest among cohorts with ≥80% HepB3 coverage (ages, 1-6 years), 2.1% (95% confidence interval, 1.1-4.3%) for anti-HBc, 0.4% (0.1-1.3%) for HBsAg, followed by 7.2% (4.1-12.4%) for anti-HBc and 2.1% (0.7-6.1%) for HBsAg among cohorts with <80% HepB3 coverage (ages, 7-8 years), by 12.0% (8.7-16.3%) for anti-HBc and 3.5% (2.2-5.6%) for HBsAg among children's cohorts not targeted for vaccination (ages, 9-14 years), and 28.9% (24.5-33.8%) for anti-HBc and 6.8% (4.5-10.1%) for HBsAg among unvaccinated adult cohorts (ages, 15-24 years). Differences across groups were significant (p<0.001, chi-square) for both markers. CONCLUSIONS: The present study demonstrates substantial impact of hepatitis B vaccine introduction on reducing HBV infections in Tajikistan. To achieve further progress in hepatitis B control, Tajikistan should maintain high routine coverage with hepatitis B vaccine, including birth dose. |
Yellow fever vaccine booster doses: recommendations of the Advisory Committee on Immunization Practices, 2015
Staples JE , Bocchini JA Jr , Rubin L , Fischer M . MMWR Morb Mortal Wkly Rep 2015 64 (23) 647-650 On February 26, 2015, the Advisory Committee on Immunization Practices (ACIP) voted that a single primary dose of yellow fever vaccine provides long-lasting protection and is adequate for most travelers. ACIP also approved recommendations for at-risk laboratory personnel and certain travelers to receive additional doses of yellow fever vaccine (Box). The ACIP Japanese Encephalitis and Yellow Fever Vaccines Workgroup evaluated published and unpublished data on yellow fever vaccine immunogenicity and safety. The evidence for benefits and risks associated with yellow fever vaccine booster doses was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This report summarizes the evidence considered by ACIP and provides the updated recommendations for yellow fever vaccine booster doses. |
Combinations of quality and frequency of immunization activities to stop and prevent poliovirus transmission in the high-risk area of Northwest Nigeria
Duintjer Tebbens RJ , Pallansch MA , Wassilak SG , Cochi SL , Thompson KM . PLoS One 2015 10 (6) e0130123 BACKGROUND: Frequent supplemental immunization activities (SIAs) with the oral poliovirus vaccine (OPV) represent the primary strategy to interrupt poliovirus transmission in the last endemic areas. MATERIALS AND METHODS: Using a differential-equation based poliovirus transmission model tailored to high-risk areas in Nigeria, we perform one-way and multi-way sensitivity analyses to demonstrate the impact of different assumptions about routine immunization (RI) and the frequency and quality of SIAs on population immunity to transmission and persistence or emergence of circulating vaccine-derived polioviruses (cVDPVs) after OPV cessation. RESULTS: More trivalent OPV use remains critical to avoid serotype 2 cVDPVs. RI schedules with or without inactivated polio vaccine (IPV) could significantly improve population immunity if coverage increases well above current levels in under-vaccinated subpopulations. Similarly, the impact of SIAs on overall population immunity and cVDPV risks depends on their ability to reach under-vaccinated groups (i.e., SIA quality). Lower SIA coverage in the under-vaccinated subpopulation results in a higher frequency of SIAs needed to maintain high enough population immunity to avoid cVDPVs after OPV cessation. CONCLUSIONS: National immunization program managers in northwest Nigeria should recognize the benefits of increasing RI and SIA quality. Sufficiently improving RI coverage and improving SIA quality will reduce the frequency of SIAs required to stop and prevent future poliovirus transmission. Better information about the incremental costs to identify and reach under-vaccinated children would help determine the optimal balance between spending to increase SIA and RI quality and spending to increase SIA frequency. |
Gender role attitudes and male adolescent dating violence perpetration: normative beliefs as moderators
Reyes HL , Foshee VA , Niolon PH , Reidy DE , Hall JE . J Youth Adolesc 2015 45 (2) 350-60 Commonly used dating violence prevention programs assume that promotion of more egalitarian gender role attitudes will prevent dating violence perpetration. Empirical research examining this assumption, however, is limited and inconsistent. The current study examined the longitudinal association between gender role attitudes and physical dating violence perpetration among adolescent boys (n = 577; 14 % Black, 5 % other race/ethnicity) and examined whether injunctive (i.e., acceptance of dating violence) and descriptive (i.e., beliefs about dating violence prevalence) normative beliefs moderated the association. As expected, the findings suggest that traditional gender role attitudes at T1 were associated with increased risk for dating violence perpetration 18 months later (T2) among boys who reported high, but not low, acceptance of dating violence (injunctive normative beliefs) at T1. Descriptive norms did not moderate the effect of gender role attitudes on dating violence perpetration. The results suggest that injunctive norms and gender role attitudes work synergistically to increase risk for dating violence perpetration among boys; as such, simultaneously targeting both of these constructs may be an effective prevention approach. |
Conflict, displacement, and IPV: findings from two Congolese refugee camps in Rwanda
Wako E , Elliott L , De Jesus S , Zotti ME , Swahn MH , Beltrami J . Violence Against Women 2015 21 (9) 1087-101 This study describes the prevalence and correlates of past-year intimate partner violence (IPV) among displaced women. We used bivariate and multivariate analyses to assess the relationships between IPV and select variables of interest. Multivariate logistic regression modeling revealed that women who had experienced outsider violence were 11 times as likely (adjusted odds ratio [AOR] = 11.21; confidence interval, CI [5.25, 23.96]) to have reported IPV than women who had not experienced outsider violence. IPV in conflict-affected settings is a major public health concern that requires effective interventions; our results suggest that women who had experienced outsider violence are at greater risk of IPV. |
Effects of Laser Printer-Emitted Engineered Nanoparticles on Cytotoxicity, Chemokine Expression, Reactive Oxygen Species, DNA Methylation, and DNA Damage: A Comprehensive in Vitro Analysis in Human Small Airway Epithelial Cells, Macrophages, and Lymphoblasts.
Pirela SV , Miousse IR , Lu X , Castranova V , Thomas T , Qian Y , Bello D , Kobzik L , Koturbash I , Demokritou P . Environ Health Perspect 2015 124 (2) 210-9 BACKGROUND: Engineered nanomaterials (ENMs) incorporated into toner formulations of printing equipment become airborne during their consumer use. Although information on the complex physicochemical and toxicological properties of both toner powders and printer-emitted particles (PEPs) continues to grow, most toxicological studies have primarily used raw toner powders rather than the actual PEPs, which are not representative of current exposures experienced at the consumer level during printing. OBJECTIVES: To assess the biological responses of a panel of human cell lines to PEPs. METHODS: Three physiologically relevant cell lines-small airway epithelial cells (SAEC), macrophages (THP-1 cells) and lymphoblasts (TK6 cells)-were exposed to PEPs at a wide range of doses (0.5-100 mug/mL) that correspond to human inhalation exposure durations at the consumer level of ~ 8 hours and higher. Following treatment, toxicological parameters reflecting distinct mechanisms were evaluated. RESULTS: PEPs caused significant membrane integrity damage, an increase in reactive oxygen species (ROS) production as well as a rise in pro-inflammatory cytokine release in different cell lines at doses relevant to exposure durations from 7.8 to 1500 hours. Furthermore, there were differences in methylation patterns that although statistically insignificant, demonstrate the potential PEPs can have on the overall epigenome following exposure. CONCLUSIONS: The in vitro findings here suggest that laser printer-emitted engineered nanoparticles may be deleterious to lung cells, and provide preliminary evidence of epigenetic modifications that might translate to pulmonary disorders. |
Macaque models of enhanced susceptibility to HIV
Henning TR , McNicholl JM , Vishwanathan SA , Kersh EN . Virol J 2015 12 (1) 90 There are few nonhuman primate models of enhanced HIV susceptibility. Such models can improve comprehension of HIV acquisition risk factors and provide rigorous testing platforms for preclinical prevention strategies. This paper reviews past, current, and proposed research on macaque HIV acquisition risk models and identifies areas where modeling is significantly lacking. We compare different experimental approaches and provide practical considerations for designing macaque susceptibility studies. Modifiable (mucosal and systemic coinfections, hormonal contraception, and rectal lubricants) and non-modifiable (hormonal fluctuations) risk factors are highlighted. Risk acquisition models via vaginal, rectal, and penile challenge routes are discussed. There is no consensus on the best statistical model for evaluating increased susceptibility, and additional research is required. The use of enhanced susceptibility macaque models would benefit multiple facets of the HIV research field, including basic acquisition and pathogenesis studies as well as the vaccine and other biomedical preventions pipeline. |
A Newly Emerged Swine-Origin Influenza A(H3N2) Variant Dampens Host Antiviral Immunity but Induces Potent Inflammasome Activation
Cao W , Mishina M , Ranjan P , De La Cruz JA , Kim JH , Garten R , Kumar A , Garcia-Sastre A , Katz JM , Gangappa S , Sambhara S . J Infect Dis 2015 212 (12) 1923-9 We compared the innate immune response to newly emerged swine origin H3N2 influenza A variant virus containing the M gene from A(H1N1)pdm09 virus (A(H3N2)vpm), with 2010 swine-origin A(H3N2)v and seasonal A(H3N2) viruses. Our results demonstrated that A(H3N2)vpM virus-induced myeloid dendritic cells secreted significantly lower levels of type I interferon (IFN) but produced significantly higher levels of pro-inflammatory cytokines and induced potent inflammasome activation. The reduction in antiviral immunity with increased inflammatory responses upon A(H3N2)vpM virus infection suggest that these viruses have the potential for increased disease severity in susceptible hosts. |
Protection Against Rectal Chimeric Simian/Human Immunodeficiency Virus Transmission in Macaques by Rectal-Specific Gel Formulations of Maraviroc and Tenofovir
Dobard CW , Taylor A , Sharma S , Anderson PL , Bushman LR , Chuong D , Pau CP , Hanson D , Wang L , Garcia-Lerma JG , McGowan I , Rohan L , Heneine W . J Infect Dis 2015 212 (12) 1988-95 BACKGROUND: Rectal HIV transmission is an important driver of the HIV epidemic. Optimally formulated gels of antiretroviral drugs are under development for preventing rectally acquired HIV. We investigated in a macaque model the pharmacokinetics and efficacy of three rectal gel formulations METHODS: Single-dose pharmacokinetics of low-osmolar 1% maraviroc (MVC), 1% tenofovir (TFV), or 1%MVC/1%TFV combination gel were evaluated in blood, rectal fluids, colorectal biopsies, and rectal lymphocytes. Efficacy was evaluated over 10 twice-weekly rectal SHIV162p3 challenges in rhesus macaques that received either placebo (n=7), MVC (n=6), TFV (n=6), or MVC/TFV (n=6) gel 30 minutes before each challenge. RESULTS: MVC and TFV were detected in plasma 30 minutes after gel application and remained above IC95 levels in rectal fluids at 24h. MVC, TFV, and TFV-DP concentrations in colorectal tissues collected up to 30 cm from the anal margin were all high at 2h, demonstrating rapid and extended tissue dosing. TFV-DP concentrations in tissue homogenates and rectal lymphocytes were highly correlated (r2=0.82). All three gel formulations were highly protective (82% efficacy; log-rank test; p≤0.02). CONCLUSION: Desirable pharmacokinetic profiles and high efficacy in this macaque model support the clinical development of these gel formulations for preventing rectal HIV infection. |
Enhanced stability of blood matrices using a dried sample spot assay to measure human butyrylcholinesterase activity and nerve agent adducts
Perez JW , Pantazides BG , Watson CM , Thomas JD , Blake TA , Johnson RC . Anal Chem 2015 87 (11) 5723-9 Dried matrix spots are safer to handle and easier to store than wet blood products, but factors such as intraspot variability and unknown sample volumes have limited their appeal as a sampling format for quantitative analyses. In this work, we introduce a dried spot activity assay for quantifying butyrylcholinesterase (BChE) specific activity which is BChE activity normalized to the total protein content in a sample spot. The method was demonstrated with blood, serum, and plasma spotted on specimen collection devices (cards) which were extracted to measure total protein and BChE activity using a modified Ellman assay. Activity recovered from dried spots was approximately 80% of the initial spotted activity for blood and >90% for plasma and serum. Measuring total protein in the sample and calculating specific activity substantially improved quantification and reduced intraspot variability. Analyte stability of nerve agent adducts was also evaluated, and the results obtained via BChE-specific activity measurements were confirmed by quantification of BChE adducts using a previously established LC-MS/MS method. The spotted samples were up to 10 times more resistant to degradation compared to unspotted control samples when measuring BChE inhibition by the nerve agents sarin and VX. Using this method, both BChE activity and adducts can be accurately measured from a dried sample spot. This use of a dried sample spot with normalization to total protein is robust, demonstrates decreased intraspot variability without the need to control for initial sample volume, and enhances analyte stability. |
Evaluation of Borrelia burgdorferi BbHtrA protease as a vaccine candidate for Lyme borreliosis in mice
Ullmann AJ , Russell TM , Dolan MC , Williams M , Hojgaard A , Weiner ZP , Johnson BJ . PLoS One 2015 10 (6) e0128868 Borrelia burgdorferi synthesizes an HtrA protease (BbHtrA) which is a surface-exposed, conserved protein within Lyme disease spirochetes with activity toward CheX and BmpD of Borrelia spp, as well as aggrecan, fibronectin and proteoglycans found in skin, joints and neural tissues of vertebrates. An antibody response against BbHtrA is observed in Lyme disease patients and in experimentally infected laboratory mice and rabbits. Given the surface location of BbHtrA on B. burgdorferi and its ability to elicit an antibody response in infected hosts, we explored recombinant BbHtrA as a potential vaccine candidate in a mouse model of tick-transmitted Lyme disease. We immunized mice with two forms of BbHtrA: the proteolytically active native form and BbHtrA ablated of activity by a serine to alanine mutation at amino acid 226 (BbHtrAS226A). Although inoculation with either BbHtrA or BbHtrAS226A produced high-titer antibody responses in C3H/HeJ mice, neither antigen was successful in protecting mice from B. burgdorferi challenge. These results indicate that the search for novel vaccine candidates against Lyme borreliosis remains a challenge. |
Bridging non-human primate correlates of protection to reassess the anthrax vaccine adsorbed booster schedule in humans
Schiffer JM , Chen L , Dalton S , Niemuth NA , Sabourin CL , Quinn CP . Vaccine 2015 33 (31) 3709-16 Anthrax vaccine adsorbed (AVA, BioThrax(R)) is approved for use in humans as a priming series of 3 intramuscular (i.m.) injections (0, 1, 6 months; 3-IM) with boosters at 12 and 18 months, and annually thereafter for those at continued risk of infection. A reduction in AVA booster frequency would lessen the burden of vaccination, reduce the cumulative frequency of vaccine associated adverse events and potentially expand vaccine coverage by requiring fewer doses per schedule. Because human inhalation anthrax studies are neither feasible nor ethical, AVA efficacy estimates are determined using cross-species bridging of immune correlates of protection (COP) identified in animal models. We have previously reported that the AVA 3-IM priming series provided high levels of protection in non-human primates (NHP) against inhalation anthrax for up to 4 years after the first vaccination. Penalized logistic regressions of those NHP immunological data identified that anti-protective antigen (anti-PA) IgG concentration measured just prior to infectious challenge was the most accurate single COP. In the present analysis, cross-species logistic regression models of this COP were used to predict probability of survival during a 43 month study in humans receiving the current 3-dose priming and 4 boosters (12, 18, 30 and 42 months; 7-IM) and reduced schedules with boosters at months 18 and 42 only (5-IM), or at month 42 only (4-IM). All models predicted high survival probabilities for the reduced schedules from 7 to 43 months. The predicted survival probabilities for the reduced schedules were 86.8% (4-IM) and 95.8% (5-IM) at month 42 when antibody levels were lowest. The data indicated that 4-IM and 5-IM are both viable alternatives to the current AVA pre-exposure prophylaxis schedule. |
Comparative dissolution of electrospun Al2O3 nanofibres in artificial human lung fluids
Shin HU , Stefaniak AB , Stojilovic N , Chase GG . Environ Sci Nano 2015 2 (3) 251-261 Sub-micron sized alumina fibres were fabricated by electrospinning and calcination of a polymer template fibre. In the calcination step, different controlled temperature heating cycles were conducted to obtain fibres of different crystalline structures. Their biodurabilities were tested at pH 7.4 with lung airway epithelial lining fluid or serum ultrafiltrate (SUF) and at pH 4.5 with macrophage phagolysosomal simulant fluid (PSF). Potential to generate free radicals was tested in vitro. Through the variation in the soak temperature from 650 [degree]C to 950 [degree]C (experiments S650-S950), the heating protocol affected the morphological characteristics, crystal structure, surface area, and density of the alumina fibres while their dissolution half-times were not significantly affected in SUF or PSF. Fibre samples formed at different heating ramp rates (experiments R93-R600) showed significant variation in the dissolution rates with the highest ramp rate corresponding to the highest dissolution rate. Thus, by increasing the calcination temperature ramp rate the alumina fibres may be produced that have reduced biodurability and lower inflammogenic potential. The fibres with the highest dissolution rated had the least aluminium content. The solubility half-times of the alumina fibres were shortest for fibres calcined at the fastest temperature ramp rate (though soak temperature did not have an effect). The ramp rates also affected the aluminium content of the fibres suggesting that the content may affect the structural strength of the fibres and control the dissolution. |
Development and characterization of mouse monoclonal antibodies against monomeric dengue virus non-structural glycoprotein 1 (NS1)
Gelanew T , Poole-Smith BK , Hunsperger E . J Virol Methods 2015 222 214-23 Dengue virus (DENV) nonstructural-1 (NS1) glycoprotein is useful for diagnosis of DENV infections in the first 8 days of illness with any of the four serotypes (DENV-1, DENV-2, DENV-3 and DENV-4). However, NS1 diagnostics are less sensitive for secondary DENV infections so the utility of NS1 diagnostics in dengue endemic countries where there is predominantly secondary infections is being questioned. Heat-mediated immunecomplex dissociation (ICD) prior to testing serum samples can significantly improve NS1 test sensitivity in secondary infections but requires monoclonal antibodies (MAbs) reactive to heat-denatured NS1. In order to incorporate a simple heat-mediated ICD step, a crucial step was to develop new MAbs with high affinity and specificity to heat-denatured DENV NS1 protein. In the present study, six new MAbs were isolated from BALB/c mice immunized with recombinant monomeric NS1 of DENV-1 and DENV-2. Characterization using three different methods: indirect ELISA, fixed cell ELISA and western blot revealed that all six MAbs are serotype-cross-reactive and capable of recognizing dimeric and hexameric isoforms as well as heat-denatured NS1 from all four DENV serotypes. No cross-reactivity to NS1 of West Nile virus and Yellow fever virus was observed on western blot and indirect ELISA. Five of the six MAbs mapped to the DENV NS1 region of 105-119 amino acids. The remaining MAb mapped to DENV NS1 region of 25-39 amino acids. These two NS1 regions were found to be highly conserved among all four DENV serotypes by sequences analysis and database comparison. These MAbs were used to develop an NS1 capture ELISA and tested using a small panel of clinical specimens. The results from the NS1 capture ELISA indicated at least a three-fold increase in NS1 antigen detection in heat-denatured samples compared to untreated specimens. Furthermore, artificial immunecomplexed results also demonstrated the binding efficiency of these MAbs to heat denatured NS1. Taken together, these MAbs allow for the incorporation of a heat dissociation step to improve the sensitivity of DENV NS1 antigen detection in secondary infections. |
State legislation, regulations, and hospital guidelines for newborn screening for critical congenital heart defects - United States, 2011-2014
Glidewell J , Olney RS , Hinton C , Pawelski J , Sontag M , Wood T , Kucik JE , Daskalov R , Hudson J . MMWR Morb Mortal Wkly Rep 2015 64 (23) 625-630 Critical congenital heart defects (CCHD) occur in approximately two of every 1,000 live births. Newborn screening provides an opportunity for reducing infant morbidity and mortality. In September 2011, the U.S. Department of Health and Human Services (HHS) Secretary endorsed the recommendation that critical congenital heart defects be added to the Recommended Uniform Screening Panel (RUSP) for all newborns. In 2014, CDC collaborated with the American Academy of Pediatrics (AAP) Division of State Government Affairs and the Newborn Screening Technical Assistance and Evaluation Program (NewSTEPs) to assess states' actions for adopting newborn screening for CCHD. Forty-three states have taken action toward newborn screening for CCHD through legislation, regulations, or hospital guidelines. Among those 43, 32 (74%) are collecting or planning to collect CCHD screening data; however, the type of data collected by CCHD newborn screening programs varies by state. State mandates for newborn screening for CCHD will likely increase the number of newborns screened, allowing for the possibility of early identification and prevention of morbidity and mortality. Data collection at the state level is important for surveillance, monitoring of outcomes, and evaluation of state CCHD newborn screening programs. |
Toward a systematic approach to generating demand for voluntary medical male circumcision: insights and results from field studies
Sgaier SK , Baer J , Rutz DC , Njeuhmeli E , Seifert-Ahanda K , Basinga P , Parkyn R , Laube C . Glob Health Sci Pract 2015 3 (2) 209-29 By the end of 2014, an estimated 8.5 million men had undergone voluntary medical male circumcision (VMMC) for HIV prevention in 14 priority countries in eastern and southern Africa, representing more than 40% of the global target. However, demand, especially among men most at risk for HIV infection, remains a barrier to realizing the program's full scale and potential impact. We analyzed current demand generation interventions for VMMC by reviewing the available literature and reporting on field visits to programs in 7 priority countries. We present our findings and recommendations using a framework with 4 components: insight development; intervention design; implementation and coordination to achieve scale; and measurement, learning, and evaluation. Most program strategies lacked comprehensive insight development; formative research usually comprised general acceptability studies. Demand generation interventions varied across the countries, from advocacy with community leaders and community mobilization to use of interpersonal communication, mid- and mass media, and new technologies. Some shortcomings in intervention design included using general instead of tailored messaging, focusing solely on the HIV preventive benefits of VMMC, and rolling out individual interventions to address specific barriers rather than a holistic package. Interventions have often been scaled-up without first being evaluated for effectiveness and cost-effectiveness. We recommend national programs create coordinated demand generation interventions, based on insights from multiple disciplines, tailored to the needs and aspirations of defined subsets of the target population, rather than focused exclusively on HIV prevention goals. Programs should implement a comprehensive intervention package with multiple messages and channels, strengthened through continuous monitoring. These insights may be broadly applicable to other programs where voluntary behavior change is essential to achieving public health benefits. |
Perspectives from the founding CDC leadership of the National Birth Defects Prevention study
Moore CA , Yoon PW , Edmonds LD , Erickson JD . Birth Defects Res A Clin Mol Teratol 2015 103 (8) 649-51 The Centers for Disease Control and Prevention (CDC) conducted its first formal case-control study to better understand the causes of major birth defects in the early 1980s (Erickson et al., 1984). The primary purpose of the study was to evaluate the possible causal contribution of paternal experiences during military service in Vietnam, with particular emphasis on exposures to the herbicide known as “Agent Orange.” The cases and controls were drawn from births that occurred in the Atlanta, Georgia area, where CDC has operated a birth defects surveillance program since 1967. The case-control design permitted evaluation of a wide array of potential maternal exposures that might cause birth defects, as well as additional paternal influences (Erickson, 1991). For example, the study identified a neural tube defect preventive benefit of periconceptional multivitamin use which paved the way for folic acid intervention to prevent neural tube defects (Mulinare et al., 1988). | Building on this experience, the CDC launched the multicenter National Birth Defects Prevention Study (NBDPS) in 1997 to advance understanding of the causes of birth defects. Because the causes of most birth defects are unknown and might be preventable if risk factors are identified, the NBDPS focused on birth defects of unknown etiology (Holmes, 1989). These included neural tube defects, congenital heart defects, orofacial clefts, limb deficiencies, abdominal wall defects, intestinal atresias, and other major birth defects that can be reliably ascertained in early infancy. One unique aspect of the NBDPS addressed the variability of birth defects classification across previous epidemiologic studies. In an effort to increase homogeneity within analytic groups of defects, clinical geneticists collaborated to develop classification guidelines that were applied across the study sites (Rasmussen et al., 2003). This and other efforts to coordinate work and maintain consistent methodology across participating Centers in multiple states, improved the power of NBDPS to identify potential causes of specific birth defects despite the relatively low prevalence of each individual defect type. This is particularly important for studying the epidemiology of birth defects because to date, exposures identified as causing birth defects have a relatively specific impact on one or a few types of birth defects rather than increasing the risk of all birth defects (Tinker, Gilboa, et al., 2015). The NBDPS methods and final counts of data collected are summarized by Reefhuis et al. in this issue (Reefhuis et al., 2015), and the strengths and weaknesses of the NBDPS have been assessed (Dolk, 2015). |
Emergency department and inpatient hospitalizations for young people with fragile X syndrome
McDermott S , Hardin JW , Royer JA , Mann JR , Tong X , Ozturk OD , Ouyang L . Am J Intellect Dev Disabil 2015 120 (3) 230-43 We compared hospital encounters between adolescents and young adults with fragile X syndrome (FXS) to peers with intellectual disability (ID) from other causes, autism spectrum disorder (ASD), and a comparison group without these conditions matched by gender, age, and insurance coverage. Those with FXS, ASD, or ID were more likely to have had hospital encounters. In terms of age groups, we found mental illness hospitalizations decreased during adulthood as compared to adolescence for those with FXS, and we found that for conditions unrelated to FXS (e.g., respiratory, genitourinary, gastroenteritis, and pneumonia) adolescents had higher rates of hospitalization compared to their peers with FXS, ID, or ASD. We analyzed epilepsy, common among people with FXS and designated as an ambulatory care sensitive condition that can be treated outside the hospital, and found that people with FXS, ID, and ASD had higher odds of hospitalization due to epilepsy in both age groups than did the comparison group. |
Congenital rubella syndrome (CRS) in Vietnam 2011-2012-CRS epidemic after rubella epidemic in 2010-2011
Toda K , Reef S , Tsuruoka M , Iijima M , Huyen DT , Hong DT , Van Cuong N , Hien NT . Vaccine 2015 33 (31) 3673-7 BACKGROUND: Rubella is endemic in Vietnam with epidemics occurring every 4-5 years. In 2011, Vietnam experienced the large nationwide rubella epidemic. During the rubella epidemic, many infants born with congenital rubella syndrome (CRS) were identified and reported from the neonatal units or cardiology departments of the national hospitals. To understand the burden of CRS, National Expanded Program on Immunization (NEPI) established sentinel CRS surveillance system. METHOD: Three national paediatric hospitals in Hanoi and Ho Chi Minh City (HCMC) were selected as CRS sentinel surveillance sites. Blood specimens from the infants were collected for rubella specific IgM and ELISA testing was performed at the national measles and rubella laboratory. RESULTS: From January 2011 to December 2012, 424 infants with suspected CRS were identified and reported. Among them 406 (96%) had specimens obtained, 284 (70%) cases were IgM positive including 279 laboratory confirmed CRS and 5 Congenital Rubella Infection (CRI). 13 cases were clinically confirmed and 127 (30%) were discarded. Total 292 infants were confirmed as CRS. Of the 292 infants with CRS, 69% of mothers had a history of "fever and rash" during pregnancy, of which 85% was in the first trimester. The most common clinical defects were congenital heart disease and cataract(s). However, 81.9% of the infants had a combination of major and minor signs and symptoms. Low birth weight in full term infants with confirmed CRS was observed in 114 infants (39%). CONCLUSIONS: The newly established CRS sentinel surveillance system documented the significant burden of CRS in Vietnam and provided evidence to the policy makers for the introduction of rubella containing vaccine (RCV) into Vietnam. This report highlights the importance of countries with rubella epidemic to establish CRS surveillance rapidly in order to support the introduction of RCV into the routine Expanded Programme on Immunization (EPI) immunization. |
Prevalence and trends in psychotropic medication use among US male veterans, 1999-2010
Frenk SM , Sautter JM , Paulose-Ram R . Pharmacoepidemiol Drug Saf 2015 24 (11) 1215-9 PURPOSE: Prior studies of psychotropic medication use among US veterans are limited in their ability to generalize estimates to the full veteran population and make comparisons with non-veterans. This study estimated the prevalence of psychotropic medication use and trends over time among male US veterans, compared their use of psychotropic medications with non-veteran males, and examined differences among veteran subpopulations. METHODS: The data for our analysis came from the National Health and Nutrition Examination Survey (1999-2010), a cross-sectional, nationally representative study of the civilian, non-institutionalized US population. RESULTS: The percentage of male veterans who used any psychotropic medication increased from 10.4% in 1999-2002 to 14.3% in 2003-2006, then remained stable in 2007-2010 (14.0%). During the same time period, the percentage of non-veteran males who used psychotropic medications remained relatively stable (7.0%, 8.3%, and 9.2%, respectively). Veterans were more likely to use psychotropic medication, specifically antidepressants, than non-veterans. The percentage of non-Hispanic white veterans and veterans aged 60 years and over who used psychotropic medications increased between 1999-2002 and 2003-2006, but the percentages remained stable between 2003-2006 and 2007-2010. In 2003-2006 and 2007-2010, a higher percentage of non-Hispanic white veterans used psychotropic medications than non-Hispanic black veterans. CONCLUSIONS: This study found that the use of psychotropic medications and antidepressants was higher among male veterans than male non-veterans, and that prevalence of use increased between 1999-2002 and 2007-2010 for male veterans but remained relatively stable for non-veterans. There were significant variations in the use of psychotropic medications among veteran subpopulations. |
The scientific basis of uncertainty factors used in setting occupational exposure limits
Dankovic DA , Naumann BD , Maier A , Dourson ML , Levy LS . J Occup Environ Hyg 2015 12 Suppl 1 0 The uncertainty factor concept is integrated into health risk assessments for all aspects of public health practice, including by most organizations that derive occupational exposure limits. The use of uncertainty factors is predicated on the assumption that a sufficient reduction in exposure from those at the boundary for the onset of adverse effects will yield a safe exposure level for at least the great majority of the exposed population, including vulnerable subgroups. There are differences in the application of the uncertainty factor approach among groups that conduct occupational assessments; however, there are common areas of uncertainty which are considered by all or nearly all occupational exposure limit-setting organizations. Five key uncertainties that are often examined include interspecies variability in response when extrapolating from animal studies to humans, response variability in humans, uncertainty in estimating a no-effect level from a dose where effects were observed, extrapolation from shorter duration studies to a full life-time exposure, and other insufficiencies in the overall health effects database indicating that the most sensitive adverse effect may not have been evaluated. In addition, a modifying factor is used by some organizations to account for other remaining uncertainties - typically related to exposure scenarios or accounting for the interplay among the five areas noted above. Consideration of uncertainties in occupational exposure limit derivation is a systematic process whereby the factors applied are not arbitrary, although they are mathematically imprecise. As the scientific basis for uncertainty factor application has improved, default uncertainty factors are now used only in the absence of chemical-specific data, and the trend is to replace them with chemical-specific adjustment factors whenever possible. The increased application of scientific data in the development of uncertainty factors for individual chemicals also has the benefit of increasing the transparency of occupational exposure limit derivation. Improved characterization of the scientific basis for uncertainty factors has led to increasing rigor and transparency in their application as part of the overall occupational exposure limit derivation process. |
Notes from the field: update: silicosis mortality - United States, 1999-2013
Mazurek JM , Schleiff PL , Wood JM , Hendricks SA , Weston A . MMWR Morb Mortal Wkly Rep 2015 64 (23) 653-654 Silicosis is a potentially fatal but preventable occupational lung disease caused by inhaling respirable crystalline silica (silica). Chronic silicosis, the most common form, occurs after exposure to relatively low silica concentrations for >10 years. Accelerated silicosis occurs after 5-10 years of exposure to higher silica levels, and acute silicosis can occur after only weeks or months of exposure to extremely high silica concentrations. New national mortality data for silicosis have become available since a previous report on silicosis surveillance was published earlier this year. CDC reviewed multiple cause-of-death mortality files from the National Center for Health Statistics to analyze deaths from silicosis (International Classification of Diseases, 10th Revision diagnosis code J62: a pneumoconiosis due to dust containing silica) reported during 1999-2013. Each record lists one underlying cause of death (the disease or injury that initiated the chain of events that led directly and inevitably to death), and up to 20 contributing causes of death (other significant conditions contributing to death but not resulting in underlying cause). Available death certificates from 35 states were reviewed for the period 2004-2006 to identify occupations associated with silicosis among decedents aged 15-44 years. Results indicate that despite substantial progress in eliminating silicosis, silicosis deaths continue to occur. Of particular concern are silicosis deaths in young adults (aged 15-44 years). These young deaths likely reflect higher exposures than those causing chronic silicosis mortality in older persons, some of sufficient magnitude to cause severe disease and death after relatively short periods of exposure. A total of 12 such deaths occurred during 2011-2013, with nine that had silicosis listed as the underlying cause of death. |
The global landscape of occupational exposure limits-implementation of harmonization principles to guide limit selection
Deveau M , Chen CP , Johanson G , Krewski D , Maier A , Niven KJ , Ripple S , Schulte PA , Silk J , Urbanus JH , Zalk DM , Niemeier RW . J Occup Environ Hyg 2015 12 Suppl 1 0 Occupational exposure limits (OELs) serve as health-based benchmarks against which measured or estimated workplace exposures can be compared. In the years since the introduction of OELs to public health practice, both developed and developing countries have established processes for deriving, setting, and using OELs to protect workers exposed to hazardous chemicals. These processes vary widely, however, and have thus resulted in a confusing international landscape for identifying and applying such limits in workplaces. The occupational hygienist will encounter significant overlap in coverage among organizations for many chemicals, while other important chemicals have OELs developed by few, if any, organizations. Where multiple organizations have published an OEL, the derived value often varies considerably-reflecting differences in both risk policy and risk assessment methodology as well as access to available pertinent data. This paper explores the underlying reasons for variability in OELs, and recommends the harmonization of risk-based methods used by OEL-deriving organizations. A framework is also proposed for the identification and systematic evaluation of OEL resources, which occupational hygienists can use to support risk characterization and risk management decisions in situations where multiple potentially relevant OELs exist. |
Identification of noise sources and design of noise reduction measures for a pneumatic nail gun
Jayakumar V , Kim J , Zechmann E . Noise Control Eng J 2015 63 (2) 159-168 An experimental-analytical procedure was implemented to reduce the operating noise level of a nail gun, a commonly found power tool in a construction site. The procedure is comprised of preliminary measurements, identification and ranking of major noise sources and application of noise controls. Preliminary measurements show that the impact noise transmitted through the structure and the exhaust related noise were found to be the first and second major contributors. Applying a noise absorbing foam on the outside of the nail gun body was found to be an effective noise reduction technique. One- and two-volume small mufflers were designed and applied to the exhaust side of the nail gun which reduced not only the exhaust noise but also the impact noise. It was shown that the overall noise level could be reduced by as much as 3.5 dB, suggesting that significant noise reduction is possible in construction power tools without any significant increase of the cost. |
Assessed occupational exposure to chlorinated, aromatic and Stoddard solvents during pregnancy and risk of fetal growth restriction
Desrosiers TA , Lawson CC , Meyer RE , Stewart PA , Waters MA , Correa A , Olshan AF . Occup Environ Med 2015 72 (8) 587-93 OBJECTIVES: Previous experimental and epidemiological research suggests that maternal exposure to some organic solvents during pregnancy may increase the risk of fetal growth restriction (FGR). We evaluated the association between expert-assessed occupational solvent exposure and risk of small for gestational age (SGA) infants in a population-based sample of women in the National Birth Defects Prevention Study. METHODS: We analysed data from 2886 mothers and their infants born between 1997 and 2002. Job histories were self-reported. Probability of exposure to six chlorinated, three aromatic and one petroleum solvent was assessed by industrial hygienists. SGA was defined as birthweight<10th centile of birthweight-by-gestational age in a national reference. Logistic regression was used to estimate ORs and 95% CIs to assess the association between SGA and exposure to any solvent(s) or specific solvent classes, adjusting for maternal age and education. RESULTS: Approximately 8% of infants were SGA. Exposure prevalence to any solvent was 10% and 8% among mothers of SGA and non-SGA infants, respectively. Among women with ≥50% probability of exposure, we observed elevated but imprecise associations between SGA and exposure to any solvent(s) (1.71; 0.86 to 3.40), chlorinated solvents (1.70; 0.69 to 4.01) and aromatic solvents (1.87; 0.78 to 4.50). CONCLUSIONS: This is the first population-based study in the USA to investigate the potential association between FGR and assessed maternal occupational exposure to distinct classes of organic solvents during pregnancy. The potential associations observed between SGA and exposure to chlorinated and aromatic solvents are based on small numbers and merit further investigation. |
Considerations for incorporating "well-being" in public policy for workers and workplaces
Schulte PA , Guerin RJ , Schill AL , Bhattacharya A , Cunningham TR , Pandalai SP , Eggerth D , Stephenson CM . Am J Public Health 2015 105 (8) e1-e14 Action to address workforce functioning and productivity requires a broader approach than the traditional scope of occupational safety and health. Focus on "well-being" may be one way to develop a more encompassing objective. Well-being is widely cited in public policy pronouncements, but often as ". . . and well-being" (e.g., health and well-being). It is generally not defined in policy and rarely operationalized for functional use. Many definitions of well-being exist in the occupational realm. Generally, it is a synonym for health and a summative term to describe a flourishing worker who benefits from a safe, supportive workplace, engages in satisfying work, and enjoys a fulfilling work life. We identified issues for considering well-being in public policy related to workers and the workplace. |
Six years of experience in entomological surveillance of indoor residual spraying against malaria transmission in Benin: lessons learned, challenges and outlooks
Akogbeto MC , Aikpon RY , Azondekon R , Padonou GG , Osse RA , Agossa FR , Beach R , Sezonlin M . Malar J 2015 14 (1) 242 BACKGROUND: From 2008 to 2013, a prevention intervention against malaria based on indoor residual spraying (IRS) was implemented in Benin. From 2008 to 2012, Ficam M(R), a bendiocarb-containing product was used for house spraying, in association with pirimiphos methyl EC (Actellic EC) in 2013. This operation aimed to strengthen the effectiveness of treated nets so as to expedite the achievement of Millennium Development Goals (MDGs): the reduction of morbidity and mortality due to malaria by 75 % from 2000 to 2015. METHODS: Monitoring and evaluation (M&E) was implemented in order to evaluate the impact of IRS intervention on malaria transmission. Anopheles gambiae s.l. populations were sampled by human landing catch. In addition, window exit traps and pyrethrum spray catches were performed to assess exophagic behaviour of Anopheles vectors the main malaria vector in the treated areas. The residual activity of insecticide in the treated walls was also assessed using WHO bioassay test. RESULTS: The purpose of this project was to draw attention to new challenges and future prospects for the success of IRS in Benin. The main strength of the intervention was a large-scale operation in which more than 80 % of the houses were treated due to the strong adhesion of population. In addition, a significant reduction of the EIR in areas under IRS were observed. However, there were many challenges including the high cost of IRS implementation and the identification of suitable areas to implement IRS. This was because of the low and short residual effect of the insecticides recommended for IRS and the management strategy for vector resistance to insecticides. This indicated that challenges are accompanied by suggested solutions. For the cost of IRS to be accessible to states, then local organizations need to be created in partnership with the National Malaria Control Programme (NMCP) in order to ensure relevant planning and implementation of IRS. CONCLUSION: As an anticipatory measure against vector resistance, this paper proposes various methods, such as periodic IRS based on a combination of two or three insecticides of different classes used in rotation every two or three years. |
Applications and limitations of Centers for Disease Control and Prevention miniature light traps for measuring biting densities of African malaria vector populations: a pooled-analysis of 13 comparisons with human landing catches
Briet OJ , Huho BJ , Gimnig JE , Bayoh N , Seyoum A , Sikaala CH , Govella N , Diallo DA , Abdullah S , Smith TA , Killeen GF . Malar J 2015 14 247 BACKGROUND: Measurement of densities of host-seeking malaria vectors is important for estimating levels of disease transmission, for appropriately allocating interventions, and for quantifying their impact. The gold standard for estimating mosquito-human contact rates is the human landing catch (HLC), where human volunteers catch mosquitoes that land on their exposed body parts. This approach necessitates exposure to potentially infectious mosquitoes, and is very labour intensive. There are several safer and less labour-intensive methods, with Centers for Disease Control light traps (LT) placed indoors near occupied bed nets being the most widely used. METHODS: This paper presents analyses of 13 studies with paired mosquito collections of LT and HLC to evaluate these methods for their consistency in sampling indoor-feeding mosquitoes belonging to the two major taxa of malaria vectors across Africa, the Anopheles gambiae sensu lato complex and the Anopheles funestus s.l. group. Both overall and study-specific sampling efficiencies of LT compared with HLC were computed, and regression methods that allow for the substantial variations in mosquito counts made by either method were used to test whether the sampling efficacy varies with mosquito density. RESULTS: Generally, LT were able to collect similar numbers of mosquitoes to the HLC indoors, although the relative sampling efficacy, measured by the ratio of LT:HLC varied considerably between studies. The overall best estimate for An. gambiae s.l. was 1.06 (95% credible interval: 0.68-1.64) and for An. funestus s.l. was 1.37 (0.70-2.68). Local calibration exercises are not reproducible, since only in a few studies did LT sample proportionally to HLC, and there was no geographical pattern or consistent trend with average density in the tendency for LT to either under- or over-sample. CONCLUSIONS: LT are a crude tool at best, but are relatively easy to deploy on a large scale. Spatial and temporal variation in mosquito densities and human malaria transmission exposure span several orders of magnitude, compared to which the inconsistencies of LT are relatively small. LT, therefore, remain an invaluable and safe alternative to HLC for measuring indoor malaria transmission exposure in Africa. |
Taking steps to a healthier nation: increasing physical activity through walking
Collins JL , Fulton JE . J Phys Act Health 2015 12 S1-S2 Physical activity offers many benefits to health, whether it be | preventing disease, contributing to emotional and cognitive health, | or helping to maintain independence later in life. 1,2 Many consider | it the “wonder drug” of health promotion. And while the benefits | are multiple, the behavior is simple. People only need to be active | for at least 150 minutes a week for adults and 60 minutes a day for | school-age youth. 2 It can even occur in short bouts, lasting at least | 10 minutes. Unfortunately, only one-half of adults3 and about one- | quarter of high school students4 are sufficiently active to realize the | health benefits of physical activity. To improve population levels | of physical activity, an increase in walking may be an important | place to start. In this supplement, titled “Walking and Walkability: | Approaches to Increase Physical Activity and Improve Health,” | the selected authors turn their attention to walking as the most | common and preferred activity for many teens and adults. Watson | et al report that 54% of US women and 41% of men cite walking as | their most common activity during the past month. 5 Similarly, Song | et al report that walking was the most frequently reported physical | activity among US high school students |
Park access among school-age youth in the United States
Harris CD , Paul P , Young R , Zhang X , Fulton JE . J Phys Act Health 2015 12 S94-S101 BACKGROUND: Fewer than 30% of U.S. youth meet the recommendation to be active ≥ 60 minutes/day. Access to parks may encourage higher levels of physical activity. PURPOSE: To examine differences in park access among U.S. school-age youth, by demographic characteristics and urbanicity of block group. METHODS: Park data from 2012 were obtained from TomTom, Incorporated. Population data were obtained from the 2010 U.S. Census and American Community Survey 2006-2010. Using a park access score for each block group based on the number of national, state or local parks within one-half mile, we examined park access among youth by majority race/ethnicity, median household income, median education, and urbanicity of block groups. RESULTS: Overall, 61.3% of school-age youth had park access-64.3% in urban, 36.5% in large rural, 37.8% in small rural, and 35.8% in isolated block groups. Park access was higher among youth in block groups with higher median household income and higher median education. CONCLUSION: Urban youth are more likely to have park access. However, park access also varies by race/ethnicity, median education, and median household. Considering both the demographics and urbanicity may lead to better characterization of park access and its association with physical activity among youth. |
Participation in types of physical activities among US adults - National Health and Nutrition Examination Survey 1999-2006
Dai S , Carroll DD , Watson KB , Paul P , Carlson SA , Fulton JE . J Phys Act Health 2015 12 S128-S140 BACKGROUND: Information on specific types of physical activities in which US adults participate is important for community and program development to promote physical activity. METHODS: Prevalence of participation and average time spent for 33 leisure-time aerobic activities and 10 activity categories were calculated using self-reported data from 22,545 participants aged ≥ 18 years in the National Health and Nutrition Examination Survey 1999-2006. RESULTS: Overall, 38% of US adults reported no leisure-time physical activities, and 43% reported 1 or 2 activities in the past 30 days. Walking was the most frequently reported activity for both men (29%) and women (38%). Among walkers, the average time spent walking was 198 minutes/week for men and 152 minutes/week for women. The most reported activities for men after walking were bicycling and yard work, and for women were aerobics and dance. For most activity categories, participation was lower among adults aged ≥ 65 years than among younger adults, and among Mexican Americans and non-Hispanic blacks than among non-Hispanic whites. Participation in most categories increased with increasing educational attainment. CONCLUSIONS: Participation in physical activity differs by types of activities and demographic characteristics. Physical activity promotion programs should take these differences into account when developing intervention strategies. |
Disparities in physical activity resource availability in six US regions
Jones SA , Moore LV , Moore K , Zagorski M , Brines SJ , Diez Roux AV , Evenson KR . Prev Med 2015 78 17-22 We conducted an ecologic study to determine physical activity resource availability overall and by sociodemographic groups in parts of six states (CA, IL, MD, MN, NC, NY). Data on parks and recreational facilities were collected from 3 sources in 2009-2012. Three measures characterized park and recreational facility availability at the census tract level: presence of ≥1 resource, number of resources, and resource kernel density. Associations between resource availability and census tract characteristics (predominant racial/ethnic group, median income, and proportion of children and older adults) were estimated using linear, binomial, and zero-inflated negative binomial regression in 2014. Pooled and stratified analyses were conducted. The study included 7,139 census tracts, comprising 9.5% of the 2010 US population. Overall the availability of parks and recreational facilities was lower in predominantly minority relative to non-Hispanic white census tracts. Low-income census tracts and those with a higher proportion of children had an equal or greater availability of park resources but fewer recreational facilities. Stratification revealed substantial variation in resource availability by state. The availability of physical activity resources varied by sociodemographic characteristics and across regions. Improved knowledge of resource distribution can inform strategies to provide equitable access to parks and recreational facilities. |
Effects of initiating a contraceptive implant on subsequent condom use: a randomized controlled trial
Rattray C , Wiener J , Legardy-Williams J , Costenbader E , Pazol K , Medley-Singh N , Snead MC , Steiner MJ , Jamieson DJ , Warner L , Gallo MF , Hylton-Kong T , Kourtis AP . Contraception 2015 92 (6) 560-6 OBJECTIVE: To evaluate whether initiation of a contraceptive implant, a method of long-acting reversible contraception (LARC), reduces condom use, as measured by a biomarker of recent semen exposure (prostate-specific antigen (PSA)). STUDY DESIGN: We conducted a randomized controlled clinical trial in which 414 Jamaican women at high risk for sexually transmitted infections (STIs) attending family planning clinics received the contraceptive implant at baseline ("immediate" insertion arm, N=208) or at the end ("delayed" insertion arm, N=206) of a three-month study period. Participants were tested for PSA at baseline and two follow-up study visits, and asked about their sexual activity and condom use. RESULTS: At baseline, 24.9% of women tested positive for PSA. At both follow-up visits, the prevalence of PSA detection did not significantly differ between the immediate versus delayed insertion arm (1-month: 26.1% vs. 20.2%; prevalence ratio (PR) = 1.3; (95% confidence interval (CI) = 0.9-1.9); 3-month: 25.6% vs. 23.1%; PR= 1.1; (95% CI = 0.8-1.6)). The change in PSA positivity over the 3 study visits was not significantly larger in the immediate arm compared to the delayed arm (1-sided p-value=0.15). CONCLUSIONS: Contraceptive implants can be successfully introduced into a population at high risk of unintended pregnancy and STIs without a biologically detectable difference in unprotected sex in the short-term. This information strengthens the evidence to support promotion of implants in such populations and can help refine counseling for promoting and maintaining use of condoms among women who choose to use implants. IMPLICATIONS: Sex unprotected by a condom was not higher over 3 months in women receiving a contraceptive implant, compared with those not receiving the implant. |
Smokeless tobacco use in India: role of prices and advertising
Kostova D , Dave D . Soc Sci Med 2015 138 82-90 Although the primary form of tobacco use worldwide is cigarette smoking, the large majority of users in India consume smokeless forms of tobacco. There is little evidence on the role of policy-related factors in shaping the demand for smokeless tobacco (ST) in India. This study evaluates the relationship between two such factors, prices and advertising, and ST use in India, using data on 67,737 individuals from the Global Adult Tobacco Survey (GATS) India 2009. We find that ST advertising is more likely to influence ST consumption in women than men, while men are more likely to respond to changes in ST price. We estimate that among adult males in India, the total price elasticity of ST demand is -0.212, which is close to estimates reported for males in the U.S. We do not find strong direct evidence on the economic substitutability or complementarity of smoked and smokeless products. However, the positive association between former smoking and current smokeless use may point to temporal substitutability at the individual level. The findings have implications on the relative effectiveness of policy tools across genders in India - increasing the prices of ST products may discourage ST use particularly among men, and advertising restrictions may play a relatively larger role in the consumption behavior of women in India. |
National and state treatment need and capacity for opioid agonist medication-assisted treatment
Jones CM , Campopiano M , Baldwin G , McCance-Katz E . Am J Public Health 2015 105 (8) e1-e9 OBJECTIVES: We estimated national and state trends in opioid agonist medication-assisted treatment (OA-MAT) need and capacity to identify gaps and inform policy decisions. METHODS: We generated national and state rates of past-year opioid abuse or dependence, maximum potential buprenorphine treatment capacity, number of patients receiving methadone from opioid treatment programs (OTPs), and the percentage of OTPs operating at 80% capacity or more using Substance Abuse and Mental Health Services Administration data. RESULTS: Nationally, in 2012, the rate of opioid abuse or dependence was 891.8 per 100 000 people aged 12 years or older compared with national rates of maximum potential buprenorphine treatment capacity and patients receiving methadone in OTPs of, respectively, 420.3 and 119.9. Among states and the District of Columbia, 96% had opioid abuse or dependence rates higher than their buprenorphine treatment capacity rates; 37% had a gap of at least 5 per 1000 people. Thirty-eight states (77.6%) reported at least 75% of their OTPs were operating at 80% capacity or more. CONCLUSIONS: Significant gaps between treatment need and capacity exist at the state and national levels. Strategies to increase the number of OA-MAT providers are needed. |
Verbal autopsy: evaluation of methods to certify causes of death in Uganda
Mpimbaza A , Filler S , Katureebe A , Quick L , Chandramohan D , Staedke SG . PLoS One 2015 10 (6) e0128801 To assess different methods for determining cause of death from verbal autopsy (VA) questionnaire data, the intra-rater reliability of Physician-Certified Verbal Autopsy (PCVA) and the accuracy of PCVA, expert-derived (non-hierarchical) and data-driven (hierarchal) algorithms were assessed for determining common causes of death in Ugandan children. A verbal autopsy validation study was conducted from 2008-2009 in three different sites in Uganda. The dataset included 104 neonatal deaths (0-27 days) and 615 childhood deaths (1-59 months) with the cause(s) of death classified by PCVA and physician review of hospital medical records (the 'reference standard'). Of the original 719 questionnaires, 141 (20%) were selected for a second review by the same physicians; the repeat cause(s) of death were compared to the original,and agreement assessed using the Kappa statistic.Physician reviewers' refined non-hierarchical algorithms for common causes of death from existing expert algorithms, from which, hierarchal algorithms were developed. The accuracy of PCVA, non-hierarchical, and hierarchical algorithms for determining cause(s) of death from all 719 VA questionnaires was determined using the reference standard. Overall, intra-rater repeatability was high (83% agreement, Kappa 0.79 [95% CI 0.76-0.82]). PCVA performed well, with high specificity for determining cause of neonatal (>67%), and childhood (>83%) deaths, resulting in fairly accurate cause-specific mortality fraction (CSMF) estimates. For most causes of death in children, non-hierarchical algorithms had higher sensitivity, but correspondingly lower specificity, than PCVA and hierarchical algorithms, resulting in inaccurate CSMF estimates. Hierarchical algorithms were specific for most causes of death, and CSMF estimates were comparable to the reference standard and PCVA. Inter-rater reliability of PCVA was high, and overall PCVA performed well. Hierarchical algorithms performed better than non-hierarchical algorithms due to higher specificity and more accurate CSMF estimates. Use of PCVA to determine cause of death from VA questionnaire data is reasonable while automated data-driven algorithms are improved. |
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