Type and dose of radiotherapy used for initial treatment of non-metastatic prostate cancer
Wang D , Ho A , Hamilton AS , Wu XC , Lo M , Fleming S , Goodman M , Thompson T , Owen J . Radiat Oncol 2014 9 (1) 47 BACKGROUND: We sought to describe patterns of initial radiotherapy among non-metastatic prostate cancer (PC) patients by recurrence risk groups. METHODS: Medical records were abstracted for a sample of 9017 PC cases diagnosed in 2004 as a part of the Center for Disease Control and Prevention's Prostate and Breast Patterns of Care Study in seven states. Non-metastatic PC cases are categorized as low-risk (LR), intermediate-risk (IR) or high-risk (HR) groups based on pretreatment PSA, tumor stage, and Gleason score per 2002 NCCN guidelines. Univariate and multivariate analyses were employed to determine factors associated with the type and dose of radiotherapy by the risk groups. RESULTS: Of the 9,017 patients, 3153 who received definitive radiotherapy either alone or in combination with hormone therapy (HT) were selected for in-depth analysis. Multivariate models showed that LR patients were more likely to receive seed implant brachytherapy (BT) than those in higher risk groups. Those in the IR group were most likely to receive external beam radiotherapy (EBRT) combined with BT or high-dose radiotherapy. Use of HT in combination with radiotherapy was more common in the IR and HR groups than for LR patients. Intensity modulated radiation treatment (IMRT) was used to treat 32.6% of PC patients treated with EBRT, with the majority (60.6%) treated with high-dose radiotherapy. CONCLUSIONS: Radiotherapy types and dosage utilization varied by PC risk groups. Patients in IR were more likely than those in LR or HR to receive high-dose radiotherapy. IMRT was used in about one third of patients to deliver high-dose radiotherapy. |
Molecular surveillance of rotavirus infection in the Democratic Republic of the Congo August 2009 to June 2012.
Pukuta ES , Esona MD , Nkongolo A , Seheri M , Makasi M , Nyembwe M , Mondonge V , Dahl BA , Mphahlele MJ , Cavallaro K , Gentsch J , Bowen MD , Waku-Kouomou D , Muyembe JJ . Pediatr Infect Dis J 2014 33 (4) 355-9 BACKGROUND: Rotavirus is a major cause of severe diarrhea worldwide. It causes 453,000 deaths in children annually. In the Democratic Republic of the Congo, sentinel site surveillance of rotavirus gastroenteritis started in 2009 and aimed to document burden of rotavirus diarrhea and identify circulating rotavirus genotypes. METHODS: Between August 2009 to June 2012, stool samples were collected in Kinshasa and Lubumbashi, from children <5 years of age who met the WHO case definition for rotavirus gastroenteritis. Rotavirus antigen detection was performed using an enzyme immunoassay technique and rotavirus strains were characterized using a multiplex reverse transcription polymerase chain reaction assay. RESULTS: During the study period, 1614 stool samples were screened for rotavirus by enzyme immunoassay and 990 (61%) were positive. Of these, the genotype was determined in 330 (33%) samples. The most common genotypes found in the samples analyzed were G1P[8] in 2009 (28%) and 2012 (33%), G2P[4] (33%) in 2010 and G2P[6] (28%) in 2011. Uncommon strains like G8P[6] (5%), G6P[6] (5%), G12P[6] (3%), G12P[8] (3%) and G8P[8] (2%) were also detected. CONCLUSIONS: In Democratic Republic of the Congo, 61% of the diarrhea in children in <5 years of age was caused by rotavirus infection and a variety of rotavirus genotypes were detected. Implementation of rotavirus genotyping at the national level has improved the timely identification of rotavirus strains. These results will help decision makers in Democratic Republic of the Congo plan the implementation of a rotavirus vaccination program. |
Rapid influenza diagnostic test use and antiviral prescriptions in outpatient settings pre- and post-2009 H1N1 pandemic
Williams LO , Kupka NJ , Schmaltz SP , Barrett S , Uyeki TM , Jernigan DB . J Clin Virol 2014 60 (1) 27-33 BACKGROUND: Rapid influenza diagnostic tests (RIDTs) can be used at the point-of-care and are often the only influenza tests readily available in outpatient facilities. OBJECTIVES: To determine the use of RIDTs and antiviral prescription practices in outpatient facilities. STUDY DESIGN: Surveys were mailed to U.S. physician's offices, emergency departments, and community health centers in 2008 (pre-2009 H1N1 pandemic) and 2010 (post-2009 H1N1 pandemic). The 2010 survey included questions to evaluate changes in testing and treatment practices among various risk groups subsequent to the 2009 H1N1 pandemic. RESULTS: In both surveys, respondents using RIDTs relied on RIDT results to guide prescribing antiviral medications. Greater than two-thirds of these respondents reported prescribing antiviral medications both pre- and post-pandemic for patients within 48h of onset of flu-like symptoms with a positive RIDT (69% pre-pandemic; 67% post-pandemic). After the pandemic (2010 survey), outpatient providers also reported prescribing antivirals to those with flu-like symptoms for 31% of children <2 years, 23% of children 2-5 years, 37% of pregnant patients, and 74% of other patients at high risk; while these figures were higher than pre-pandemic, they represent a failure to use CDC guidelines to prescribe antivirals for patients with suspected influenza who are at higher risk for complications. CONCLUSIONS: Clinicians in outpatient facilities often relied on RIDT findings to aid in making antiviral treatment decisions; however their treatment practices were not always consistent with CDC guidelines. The use of RIDTs and antiviral medicines were influenced by the 2009 H1N1 pandemic. |
Trends in tuberculosis - United States, 2013
Alami NN , Yuen CM , Miramontes R , Pratt R , Price SF , Navin TR . MMWR Morb Mortal Wkly Rep 2014 63 (11) 229-33 In 2013, a total of 9,588 new tuberculosis (TB) cases were reported in the United States, with an incidence rate of 3.0 cases per 100,000 population, a decrease of 4.2% from 2012. This report summarizes provisional TB surveillance data reported to CDC in 2013. Although case counts and incidence rates continue to decline, certain populations are disproportionately affected. The TB incidence rate among foreign-born persons in 2013 was approximately 13 times greater than the incidence rate among U.S.-born persons, and the proportion of TB cases occurring in foreign-born persons continues to increase, reaching 64.6% in 2013. Racial/ethnic disparities in TB incidence persist, with TB rates among non-Hispanic Asians almost 26 times greater than among non-Hispanic whites. Four states (California, Texas, New York, and Florida), home to approximately one third of the U.S. population, accounted for approximately half the TB cases reported in 2013. The proportion of TB cases occurring in these four states increased from 49.9% in 2012 to 51.3% in 2013. Continued progress toward TB elimination in the United States will require focused TB control efforts among populations and in geographic areas with disproportionate burdens of TB. |
Prevalence and public health implications of state laws that criminalize potential HIV exposure in the United States
Lehman JS , Carr MH , Nichol AJ , Ruisanchez A , Knight DW , Langford AE , Gray SC , Mermin JH . AIDS Behav 2014 18 (6) 997-1006 For the past three decades, legislative approaches to prevent HIV transmission have been used at the national, state, and local levels. One punitive legislative approach has been enactment of laws that criminalize behaviors associated with HIV exposure (HIV-specific criminal laws). In the USA, HIV-specific criminal laws have largely been shaped by state laws. These laws impose criminal penalties on persons who know they have HIV and subsequently engage in certain behaviors, most commonly sexual activity without prior disclosure of HIV-positive serostatus. These laws have been subject to intense public debate. Using public health law research methods, data from the legal database WestlawNext(c) were analyzed to describe the prevalence and characteristics of laws that criminalize potential HIV exposure in the 50 states (plus the District of Columbia) and to examine the implications of these laws for public health practice. The first state laws were enacted in 1986; as of 2011 a total of 67 laws had been enacted in 33 states. By 1995, nearly two-thirds of all laws had been enacted; by 2000, 85 % of laws had been enacted; and since 2000, an additional 10 laws have been enacted. Twenty-four states require persons who are aware that they have HIV to disclose their status to sexual partners and 14 states require disclosure to needle-sharing partners. Twenty-five states criminalize one or more behaviors that pose a low or negligible risk for HIV transmission. Nearly two-thirds of states in the USA have legislation that criminalizes potential HIV exposure. Many of these laws criminalize behaviors that pose low or negligible risk for HIV transmission. The majority of laws were passed before studies showed that antiretroviral therapy (ART) reduces HIV transmission risk and most laws do not account for HIV prevention measures that reduce transmission risk, such as condom use, ART, or pre-exposure prophylaxis. States with HIV-specific criminal laws are encouraged to use the findings of this paper to re-examine those laws, assess the laws' alignment with current evidence regarding HIV transmission risk, and consider whether the laws are the best vehicle to achieve their intended purposes. |
Epidemiology of tuberculosis in young children in the United States
Pang J , Teeter LD , Katz DJ , Davidow AL , Miranda W , Wall K , Ghosh S , Stein-Hart T , Restrepo BI , Reves R , Graviss EA . Pediatrics 2014 133 (3) e494-504 OBJECTIVES: To estimate tuberculosis (TB) rates among young children in the United States by children's and parents' birth origins and describe the epidemiology of TB among young children who are foreign-born or have at least 1 foreign-born parent. METHODS: Study subjects were children <5 years old diagnosed with TB in 20 US jurisdictions during 2005-2006. TB rates were calculated from jurisdictions' TB case counts and American Community Survey population estimates. An observational study collected demographics, immigration and travel histories, and clinical and source case details from parental interviews and health department and TB surveillance records. RESULTS: Compared with TB rates among US-born children with US-born parents, rates were 32 times higher in foreign-born children and 6 times higher in US-born children with foreign-born parents. Most TB cases (53%) were among the 29% of children who were US born with foreign-born parents. In the observational study, US-born children with foreign-born parents were more likely than foreign-born children to be infants (30% vs 7%), Hispanic (73% vs 37%), diagnosed through contact tracing (40% vs 7%), and have an identified source case (61% vs 19%); two-thirds of children were exposed in the United States. CONCLUSIONS: Young children who are US born of foreign-born parents have relatively high rates of TB and account for most cases in this age group. Prompt diagnosis and treatment of adult source cases, effective contact investigations prioritizing young contacts, and targeted testing and treatment of latent TB infection are necessary to reduce TB morbidity in this population. |
Extragenital gonorrhea and chlamydia testing and infection among men who have sex with men - STD Surveillance Network, United States, 2010-2012
Patton ME , Kidd S , Llata E , Stenger M , Braxton J , Asbel L , Bernstein K , Gratzer B , Jespersen M , Kerani R , Mettenbrink C , Mohamed M , Pathela P , Schumacher C , Stirland A , Stover J , Tabidze I , Kirkcaldy RD , Weinstock H . Clin Infect Dis 2014 58 (11) 1564-70 BACKGROUND: Gonorrhea (GC) and chlamydia (CT) are the most commonly reported notifiable diseases in the U.S. CDC recommends that men who have sex with men (MSM) be screened for urogenital GC/CT, rectal GC/CT, and pharyngeal GC. We describe extragenital GC/CT testing and positivity among MSM attending sexually transmitted disease (STD) clinics. METHODS: The STD Surveillance Network collects patient data from 42 STD clinics. We assessed the proportion of MSM attending these clinics during July 2011-June 2012 who were tested and positive for extragenital GC/CT at their most recent visit or in the preceding 12 months and the number of extragenital infections that would have remained undetected with urethral screening alone. RESULTS: Of 21,994 MSM, 83.9% were tested for urogenital GC, 65.9% for pharyngeal GC, 50.4% for rectal GC, 81.4% for urogenital CT, 31.7% for pharyngeal CT, and 45.9% for rectal CT. Of MSM tested, 11.1% tested positive for urogenital GC, 7.9% for pharyngeal GC, 10.2% for rectal GC, 8.4% for urogenital CT, 2.9% for pharyngeal CT, and 14.1% for rectal CT. Over 70% of extragenital GC infections and 85% of extragenital CT infections were associated with negative urethral tests at the same visit and would not have been detected with urethral screening alone. CONCLUSIONS: Extragenital GC/CT was common among MSM attending STD clinics, but many MSM were not tested. Most extragenital infections would not have been identified, and likely would have remained untreated, with urethral screening alone. Efforts are needed to facilitate implementation of extragenital GC/CT screening recommendations for MSM. |
Implementation of new TB screening requirements for U.S.-bound immigrants and refugees - 2007-2014
Posey DL , Naughton MP , Willacy EA , Russell M , Olson CK , Godwin CM , McSpadden PS , White ZA , Comans TW , Ortega LS , Guterbock M , Weinberg MS , Cetron MS . MMWR Morb Mortal Wkly Rep 2014 63 (11) 234-6 For more than two decades, as the number of tuberculosis (TB) cases overall in the United States has declined, the proportion of cases among foreign-born persons has increased. In 2013, the percentage of TB cases among those born outside the country was 64.6%. To address this trend, CDC has developed strategies to identify and treat TB in U.S.-bound immigrants and refugees overseas. Each year, approximately 450,000 persons are admitted to the United States on an immigrant visa, and 50,000-70,000 are admitted as refugees. Applicants for either an immigrant visa or refugee status are required to undergo a medical examination overseas before being allowed to travel to the United States. CDC is the federal agency with regulatory oversight of the overseas medical examination, and panel physicians appointed by the U.S. Department of State perform the examinations in accordance with Technical Instructions (TI) provided by CDC's Division of Global Migration and Quarantine (DGMQ). Beginning in 1991, the algorithm for TB TI relied on chest radiographs for applicants aged ≥15 years, followed by sputum smears for those with findings suggestive of TB; no additional diagnostics were used. In 2007, CDC issued enhanced standards for TB diagnosis and treatment, including the addition of sputum cultures (which are more sensitive than smears) as a diagnostic tool and treatment delivered as directly observed therapy (DOT). This report summarizes worldwide implementation of the new screening requirements since 2007. In 2012, the year for which the most recent data are available, 60% of the TB cases diagnosed were in persons with smear-negative, but culture-positive, test results. The results demonstrate that rigorous diagnostic and treatment programs can be implemented in areas with high TB incidence overseas. |
Child, household, and caregiver characteristics associated with hospitalization for influenza among children 6-59 months of age: an Emerging Infections Program study
Dharan NJ , Sokolow LZ , Cheng PY , Gargiullo P , Gershman K , Lynfield R , Morin C , Thomas A , Meek J , Farley MM , Arnold KE , Reingold A , Craig AS , Schaffner W , Bennett NM , Zansky S , Baumbach J , Lathrop S , Kamimoto L , Shay DK . Pediatr Infect Dis J 2014 33 (6) e141-50 BACKGROUND: Young children are at increased risk of severe outcomes from influenza illness, including hospitalization. We conducted a case-control study to identify risk factors for influenza-associated hospitalizations among children in U.S. Emerging Infections Program sites. METHODS: Cases were children 6-59 months of age hospitalized for laboratory-confirmed influenza infections during 2005-08. Age- and zip-code-matched controls were enrolled. Data on child, caregiver, and household characteristics were collected from parents and medical records. Conditional logistic regression was used to identify independent risk factors for hospitalization. RESULTS: We enrolled 290 (64%) of 454 eligible cases and 1,089 (49%) of 2,204 eligible controls. Risk for influenza hospitalization increased with maternal age <26 years (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1-2.9); household income below the poverty threshold (OR 2.2, CI 1.4-3.6); smoking by >50% of household members (OR 2.9, CI 1.4-6.6); lack of household influenza vaccination (OR 1.8, CI 1.2-2.5); and presence of chronic illnesses, including hematologic/oncologic (OR 11.8, CI 4.5-31.0), pulmonary (OR 2.9, CI 1.9-4.4), and neurologic (OR 3.8, CI 1.6-9.2) conditions. Full influenza immunization decreased the risk among children aged 6-23 months (OR 0.5, CI 0.3-0.9) but not among those 24-59 months of age (OR 1.5, CI 0.8-3.0; p-value for difference = 0.01). CONCLUSIONS: Chronic illnesses, young maternal age, poverty, household smoking, and lack of household influenza vaccination increased the risk of influenza hospitalization. These characteristics may help providers to identify young children who are at greatest risk for severe outcomes from influenza illness. |
Knowledge, attitudes, and practices of US practitioners who provide pre-travel advice
Kogelman L , Barnett ED , Chen LH , Quinn E , Yanni E , Wilson ME , Benoit C , Karchmer AW , Ooi WW , Jentes ES , Hamer DH . J Travel Med 2014 21 (2) 104-14 BACKGROUND: As international travel increases, many health care professionals are being asked to provide pre-travel advice. We designed an anonymous web-based survey to assess the extent to which primary care providers (PCPs) provide travel medicine advice and how their understanding and delivery of itinerary-specific advice and management compare with that of travel medicine specialists. METHODS: We surveyed randomly selected US PCPs registered in the Pri-Med Institute (now pmiCME) database and US travel medicine specialists from the International Society of Travel Medicine (ISTM), American Society of Tropical Medicine and Hygiene (ASTMH), and Centers for Disease Control and Prevention (CDC) yellow fever (YF) vaccine provider mailing lists. SAS software (SAS Institute, Cary, NC, USA) was used for all analyses. RESULTS: Of 14,932 e-mails sent to valid e-mail addresses, 902 yielded complete or partially completed surveys (6.0% response rate). Eighty percent of respondents personally provided pre-travel advice (95% of travel medicine specialists versus 73% of PCPs). About two thirds of PCPs (68%) providing pre-travel consultations saw <50 travelers per year whereas 30% of travel medicine specialists saw <50 travelers per year. More travel medicine specialists (59%) than PCPs (18%) saw >500 travelers per year. Familiarity with travel-specific vaccines (YF, Japanese encephalitis) and provision of written educational materials increased as volume of travelers increased. Familiarity with antimalarial side effects and malaria resistance patterns, and knowledge scores based on brief pre-travel scenarios were higher in travel medicine specialists, ASTMH or ISTM certificate holders, and respondents who saw more pre-travel patients. CONCLUSIONS: Many PCP survey participants provided pre-travel advice, but most saw few travelers. Volume of travelers and holding an ASTMH or ISTM certificate had the greatest influence on knowledge of travel medicine and provision of appropriate advice and recommendations. Creating easily accessible travel medicine education programs for US providers from a wide range of disciplines is needed to improve the management of travelers. |
Preparedness and health risks associated with Moulay Abdellah Amgharmoussem, Morocco, 2009-2010
Youbi M , Dghoughi N , Akrim M , Essolbi A , Barkia A , Azami AI , Fleischauer AT , Schneider D , Maaroufi A . East Mediterr Health J 2013 19 S19-S23 The objective of this study was to describe the risks and human health outcomes associated with attendance at the Moulay Abdellah Amghar moussem (a pre-planned mass gathering attracting more than 360 000 participants) for the purposes of public health prevention, planning, preparedness and response. We performed an environmental health risk assessment and retrospectively reviewed local health centre records before, during and after the event. In addition, standardized interviews with key stakeholders were performed to qualitatively evaluate local public health preparedness and response capacities. During the event, average daily health centre visits increased 5-fold. The sex ratio of health-care visits changed significantly from an average of 1.8:1 female:male visits per day to 1.2:1. The proportion of injuries varied from an average of 3.7% pre- and post-event to 14.8% (P < 0.01) during the event. A significant increase in digestive diseases was also observed during the event. Recommendations include increasing accessibility to free sanitation and hygiene facilities and improving health communications concerning hand washing and food and water safety. |
Reduction of the body burden of PCBs and DDE by dietary intervention in a randomized trial
Jandacek RJ , Heubi JE , Buckley DD , Khoury JC , Turner WE , Sjodin A , Olson JR , Shelton C , Helms K , Bailey TD , Carter S , Tso P , Pavuk M . J Nutr Biochem 2014 25 (4) 483-8 Serum polychlorinated biphenyls (PCBs) in Anniston, AL, residents have been associated with hypertension and diabetes. There have been no systematic interventions to reduce PCB body burdens in Anniston or other populations. Our objective was to determine the efficacy of 15 g/day of dietary olestra to reduce PCBs in Anniston residents. Blood PCBs and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene were measured at baseline and 4-month intervals in a double-blind, placebo-controlled, 1-year trial. Participants with elevated serum PCBs were randomized into two groups of 14 and received potato crisps made with olestra or vegetable oil (VO). Elimination rates during the study period were compared with 5-year prestudy rates. Eleven participants in the olestra group and 12 in the VO group completed the study. Except for one participant in the VO group, reasons for dropout were unrelated to treatments. The elimination rate of 37 non-coplanar PCB congeners during the 1-year trial was faster during olestra consumption compared to the pretrial period (-0.0829+/-0.0357 and -0.00864+/-0.0116 year(-1), respectively; P=.04), but not during VO consumption (-0.0413+/-0.0408 and -0.0283+/-0.0096 year(-1), respectively; P=.27). The concentration of PCBs in two olestra group participants decreased by 27% and 25% during the trial. There was no significant time by group interaction in change from baseline. However, group main effects for total PCBs and PCB 153 were of borderline significance. This pilot study has demonstrated that olestra can safely reduce body burdens of PCBs and supports a larger intervention trial that may also determine whether reduction in PCBs will reduce the risk of hypertension and diabetes. |
Residential traffic exposure and childhood leukemia: a systematic review and meta-analysis
Boothe VL , Boehmer TK , Wendel AM , Yip FY . Am J Prev Med 2014 46 (4) 413-22 CONTEXT: Exposure to elevated concentrations of traffic-related air pollutants in the near-road environment is associated with numerous adverse human health effects, including childhood cancer, which has been increasing since 1975. Results of individual epidemiologic studies have been inconsistent. Therefore, a meta-analysis was performed to examine the association between residential traffic exposure and childhood cancer. EVIDENCE ACQUISITION: Studies published between January 1980 and July 2011 were retrieved from a systematic search of 18 bibliographic databases. Nine studies meeting the inclusion criteria were identified. Weighted summary ORs were calculated using a random effects model for outcomes with four or more studies. Subgroup and sensitivity analyses were performed. EVIDENCE SYNTHESIS: Childhood leukemia was positively associated (summary OR=1.53, 95% CI=1.12, 2.10) with residential traffic exposure among seven studies using a postnatal exposure window (e.g., childhood period or diagnosis address) and there was no association (summary OR=0.92, 95% CI=0.78, 1.09) among four studies using a prenatal exposure window (e.g., pregnancy period or birth address). There were too few studies to analyze other childhood cancer outcomes. CONCLUSIONS: Current evidence suggests that childhood leukemia is associated with residential traffic exposure during the postnatal period, but not during the prenatal period. Additional well-designed epidemiologic studies that use complete residential history to estimate traffic exposure, examine leukemia subtypes, and control for potential confounding factors are needed to confirm these findings. As many people reside near busy roads, especially in urban areas, precautionary public health messages and interventions designed to reduce population exposure to traffic might be warranted. |
Predictors of blood trihalomethane concentrations in NHANES 1999-2006
Riederer AM , Dhingra R , Blount BC , Steenland K . Environ Health Perspect 2014 122 (7) 695-702 BACKGROUND: Trihalomethanes (THMs) are water disinfection by-products that have been associated with bladder cancer and adverse birth outcomes. Four (bromoform, chloroform, bromodichloromethane, dibromochloromethane) were measured in blood and tap water of U.S. adults in NHANES 1999-2006. THMs are metabolized to potentially toxic/mutagenic intermediates by cytochrome p450 (CYP) 2D6 and CYP2E1 enzymes. OBJECTIVES: We conducted exploratory analyses of blood THMs including factors affecting CYP2D6 and CYP2E1 activity. METHODS: We used weighted multivariable regression to evaluate associations between blood THMs and water concentrations, survey year, and other factors potentially affecting THM exposure or metabolism (e.g., prescription medications, cruciferous vegetables, diabetes, fasting, pregnancy, swimming). RESULTS: From 1999-2006, geometric mean blood and water THM levels dropped in parallel-32%-76% in blood and 38%-52% in water-likely resulting, in part, from the lowering of the total THM drinking water standard in 2002-2004. The strongest predictors of blood THM levels were survey year and water concentration (N=4,232 total THM; N=4,582 chloroform; N=4,080 bromoform; N=4,374 bromodichloromethane; N=4,464 dibromochloromethane). Statistically significant inverse associations were detected with diabetes and eating cruciferous vegetables in all but the bromoform model. Medications did not consistently predict blood levels. Afternoon/evening blood samples had lower THM concentrations than morning samples. In a sub-sample (n=230), air chloroform better predicted blood chloroform than water chloroform, suggesting showering/bathing was a more important source than drinking. CONCLUSIONS: We identified several factors associated with blood THMs which may be factors affecting their metabolism; potential health implications require further study. |
National surveillance for haemophilia inhibitors in the United States: summary report of an expert meeting
Soucie JM , Miller CH , Kelly FM , Aschman D , Dimichele D , Konkle BA , Kulkarni R , Monahan PE . Am J Hematol 2014 89 (6) 621-5 On March 12, 2012, the Centers for Disease Control and Prevention (CDC) held a meeting of its partners in haemophilia treatment, community-based organizations, industry, and government to review data and discuss implementation issues relevant to planned United States (U.S.) national inhibitor surveillance. Issues discussed included the current status of inhibitor surveillance in the United Kingdom (U.K.) and the U.S., the results of a U.S. inhibitor surveillance feasibility study, proposed national surveillance schemes, laboratory testing and reporting issues and potential opportunities for future inhibitor-related research. It was concluded that implementation of a national program of inhibitor surveillance using standardized testing through an established public health registry along with patient and care provider education and targeted research provide the best opportunity to inform efforts to develop and evaluate effective prevention strategies. |
Pattern of morbidity and mortality in Karbala hospitals during Ashura mass gathering at Karbala, Iraq, 2010
Al-Lami F , Al-Fatlawi A , Bloland P , Nawwar A , Jetheer A , Hantoosh H , Radhi F , Mohan B , Abbas M , Kamil A , Khayatt I , Baqir H . East Mediterr Health J 2013 19 S13-S18 Religious mass gatherings are increasingly common in Iraq and can harbour considerable public health risks. This study was aimed at determining morbidity and mortality patterns in hospitals in Karbala city, Iraq during the mass gathering for Ashura in 2010. We conducted a cross-sectional study on attendees at the 3 public hospitals in the city. The study period was divided into pre-event, event, and post-event phases. Morbidity and mortality data were obtained from hospital registry books and the coroners office. About 80% of the 18 415 consultations were at emergency rooms. Average daily emergency room attendance was higher during the event compared with pre- and post-event phases, while average daily admissions decreased. Compared with the pre-event phase, a 7-fold increase in febrile disorders and a 2-fold increase in chronic diseases and injuries were noted during the event phase. There was no difference between the 3 phases for average daily death rate,nor for cause of death. |
Recombinant viruses initiated the early HIV-1 epidemic in Burkina Faso.
Fonjungo PN , Kalish ML , Schaefer A , Rayfield M , Mika J , Rose LE , Heslop O , Soudre R , Pieniazek D . PLoS One 2014 9 (3) e92423 We analyzed genetic diversity and phylogenetic relationships among 124 HIV-1 and 19 HIV-2 strains in sera collected in 1986 from patients of the state hospital in Ouagadougou, Burkina Faso. Phylogenetic analysis of the HIV-1 env gp41 region of 65 sequences characterized 37 (56.9%) as CRF06_cpx strains, 25 (38.5%) as CRF02_AG, 2 (3.1%) as CRF09_cpx, and 1 (1.5%) as subtype A. Similarly, phylogenetic analysis of the protease (PR) gene region of 73 sequences identified 52 (71.2%) as CRF06_cpx, 15 (20.5%) as CRF02_AG, 5 (6.8%) as subtype A, and 1 (1.4%) was a unique strain that clustered along the B/D lineage but basal to the node connecting the two lineages. HIV-2 PR or integrase (INT) groups A (n = 17 [89.5%]) and B (n = 2 [10.5%]) were found in both monotypic (n = 11) and heterotypic HIV-1/HIV-2 (n = 8) infections, with few HIV-2 group B infections. Based on limited available sampling, evidence suggests two recombinant viruses, CRF06_cpx and CRF02_AG, appear to have driven the beginning of the mid-1980s HIV-1 epidemic in Burkina Faso. |
Clostridium botulinum strains producing BoNT/F4 or BoNT/F5.
Raphael BH , Bradshaw M , Kalb SR , Joseph LA , Luquez C , Barr JR , Johnson EA , Maslanka SE . Appl Environ Microbiol 2014 80 (10) 3250-7 Botulinum neurotoxin type F (BoNT/F) may be produced by Clostridium botulinum alone or in combination with another toxin type such as types A or B. Type F neurotoxin gene sequences have been further classified into 7 toxin subtypes. Recently, the genome sequence of one strain of C. botulinum (Af84) was shown to contain three neurotoxin genes (bont/F4, bont/F5, and bont/A2). In this study, a total of 8 strains containing bont/F4 and 7 strains containing bont/F5 were examined. Culture supernatants produced by these strains were incubated with BoNT/F-specific peptide substrates. Cleavage products of these peptides were subjected to mass spectral analysis allowing detection of the BoNT/F subtypes present in the culture supernatants. PCR analysis demonstrated that a plasmid-specific marker (PL-6) was observed only among strains containing bont/F5. Among these strains, Southern hybridization revealed the presence of an approximately 242-kb plasmid harboring bont/F5-. Genome sequencing of four of these strains revealed that the genomic backgrounds of strains harboring either bont/F4 or bont/F5 are diverse. None of the strains analyzed in this study were shown to produce BoNT/F4 and BoNT/F5 simultaneously suggesting that strain Af84 is unusual. Finally, these data support a role for the mobility of a bont/F5-encoding plasmid among strains of diverse genomic backgrounds. |
Notes from the field: a cluster of lymphocytic choriomeningitis virus infections transmitted through organ transplantation - Iowa, 2013
Schafer IJ , Miller R , Stroher U , Knust B , Nichol ST , Rollin PE . MMWR Morb Mortal Wkly Rep 2014 63 (11) 249 On April 26, 2013, the United Network for Organ Sharing reported to CDC a cluster of ill organ transplant recipients in Iowa with a common organ donor. Infection with lymphocytic choriomeningitis virus (LCMV) was suspected. LCMV is a rodent-borne virus that most commonly causes nonfatal, influenza-like illness and occasional aseptic meningitis, but when transmitted through organ transplantation or in utero can cause severe, life-threatening disease. |
Infection control and bloodstream infection prevention: the perspective of patients receiving hemodialysis
See I , Shugart A , Lamb C , Kallen AJ , Patel PR , Sinkowitz-Cochran RL . Nephrol Nurs J 2014 41 (1) 37-+ Patients on hemodialysis, particularly those dialyzed through central lines, are at risk of acquiring bloodstream infections. Strategies to prevent bloodstream infections in patients on dialysis include educating patients about infection prevention, although patients' perspectives on this topic are not known. During focus groups conducted to explore these issues, patients reported that education on infection prevention should begin early in the process of dialysis, and that patients should be actively engaged as partners in infection prevention. |
Risk of fever after pediatric trivalent inactivated influenza vaccine and 13-valent pneumococcal conjugate vaccine
Stockwell MS , Broder K , Larussa P , Lewis P , Fernandez N , Sharma D , Barrett A , Sosa J , Vellozzi C . JAMA Pediatr 2014 168 (3) 211-9 IMPORTANCE: An observational study found an increased risk of febrile seizure on the day of or 1 day after vaccination (days 0-1) with trivalent inactivated influenza vaccine (TIV) in the 2010-2011 season; risk was highest with simultaneous vaccination with TIV and 13-valent pneumococcal vaccine (PCV13) in children who were 6 to 23 months old. Text messaging is a novel method for surveillance of adverse events after immunization that has not been used for hypothesis-driven vaccine safety research. OBJECTIVE: To prospectively evaluate whether children receiving TIV and PCV13 simultaneously had higher rates of fever on days 0 to 1 than those receiving either product without the other. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational cohort study of parents of children 6 to 23 months old recruited from 3 medical center-affiliated clinics in New York City from November 1, 2011, through April 5, 2012. A total of 530 of 614 eligible participants (86.3%) were enrolled. Parents were texted on the night of vaccination (day 0) and the 7 subsequent nights (days 1-7) to report their child's temperature. We used log-binomial regression to calculate adjusted relative risks (aRRs) and excess risk for fever on days 0 to 1, adjusted for age group, past influenza vaccination and simultaneous receipt of selected inactivated vaccines. EXPOSURES: Receipt of TIV and/or PCV13. MAIN OUTCOME(S) AND MEASURE(S): Temperature of 38 degrees C or higher on days 0 to 1 after vaccination. RESULTS: On days 0 to 1, children receiving TIV and PCV13 simultaneously had higher rates (37.6%) of fever (temperature ≥38 degrees C) than those receiving TIV (7.5%; aRR, 2.69; 95% CI, 1.30-5.60) or PCV13 (9.5%; aRR, 2.67; 95% CI, 1.25-5.66). The excess risk of fever after TIV and PCV13 was 20 and 23 per 100 vaccinations compared with TIV without PCV13 and PCV13 without TIV, respectively. Fever rates for days 2 to 7 were similar across groups. For days 0 to 1, 74.8% of the text messages were confirmed delivered; for another 9.0%, delivery status was unknown. Response rates were 95.1% and 90.9% for days 0 and 1 for confirmed delivered messages, respectively. CONCLUSIONS AND RELEVANCE: Simultaneous TIV and PCV13 administration was associated with higher transient increased fever risk than administration of either vaccine without the other product. Text messaging to prospectively assess a specific vaccine adverse event has potential for enhancing prelicensure and postlicensure monitoring of adverse events after immunization and deserves further study. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01467934. |
Update on vaccine-derived polioviruses - worldwide, July 2012-December 2013
Diop OM , Burns CC , Wassilak SG , Kew OM . MMWR Morb Mortal Wkly Rep 2014 63 (11) 242-8 In 1988, the World Health Assembly resolved to eradicate poliomyelitis worldwide. One of the main tools used in polio eradication efforts has been live, attenuated oral poliovirus vaccine (OPV), an inexpensive vaccine easily administered by trained volunteers. OPV might require several doses to induce immunity, but then it provides long-term protection against paralytic disease through durable humoral immunity. Rare cases of vaccine-associated paralytic poliomyelitis can occur among immunologically normal OPV recipients, their contacts, and persons who are immunodeficient. In addition, vaccine-derived polioviruses (VDPVs) can emerge in areas with low OPV coverage to cause polio outbreaks and can replicate for years in persons who have primary, B-cell immunodeficiencies. This report updates previous surveillance summaries and describes VDPVs detected worldwide during July 2012-December 2013. Those include a new circulating VDPV (cVDPV) outbreak identified in Pakistan in 2012, with spread to Afghanistan; an outbreak in Afghanistan previously identified in 2009 that continued into 2013; a new outbreak in Chad that spread to Cameroon, Niger, and northeastern Nigeria; and an outbreak that began in Somalia in 2008 that continued and spread to Kenya in 2013. A large outbreak in Nigeria that was identified in 2005 was nearly stopped by the end of 2013. Additionally, 10 newly identified persons in eight countries were found to excrete immunodeficiency-associated VDPVs (iVDPVs), and VDPVs were found among immunocompetent persons and environmental samples in 13 countries. Because the majority of VDPV isolates are type 2, the World Health Organization has developed a plan for coordinated worldwide replacement of trivalent OPV (tOPV) with bivalent OPV (bOPV; types 1 and 3) by 2016, preceded by introduction of at least 1 dose of inactivated poliovirus vaccine (IPV) containing all three poliovirus serotypes into routine immunization schedules worldwide to ensure high population immunity to all polioviruses. |
Prediction and characterization of helper T-cell epitopes from pneumococcal surface adhesin A
Singh R , Gupta P , Sharma PK , Ades EW , Hollingshead SK , Singh S , Lillard JW . Immunology 2014 141 (4) 514-530 Pneumococcal surface adhesin A (PsaA) is a multifunctional lipoprotein known to bind nasopharyngeal epithelial cells, and is significantly involved in bacterial adherence and virulence. Identification of PsaA peptides that optimally bind human leucocyte antigen (HLA) and elicit a potent immune response would be of great importance to vaccine development. However, this is hindered by the multitude of HLA polymorphisms in humans. To identify the conserved immunodominant epitopes, we used an experimental dataset of 28 PsaA synthetic peptides and in silico methods to predict specific peptide-binding to HLA and murine MHC class II molecules. We also characterized spleen and cervical lymph node (CLN) -derived T helper (Th) lymphocyte cytokine responses to these peptides after Streptococcus pneumoniae strain EF3030 challenge in mice. Individual, yet overlapping, peptides 15 amino acids in length revealed residues of PsaA that consistently caused the highest interferon-gamma, interleukin-2 (IL-2), IL-5 and IL-17 responses and proliferation as well as moderate IL-10 and IL-4 responses by ex vivo re-stimulated splenic and CLN CD4+ T cells isolated from S. pneumoniae strain EF3030-challenged F1 (B6 x BALB/c) mice. In silico analysis revealed that peptides from PsaA may interact with a broad range of HLA-DP, -DQ and -DR alleles, due in part to regions lacking beta-turns and asparagine endopeptidase sites. These data suggest that Th cell peptides (7, 19, 20, 22, 23 and 24) screened for secondary structures and MHC class II peptide-binding affinities can elicit T helper cytokine and proliferative responses to PsaA peptides. |
Evaluation of the antigenic relatedness and cross-protective immunity of the neuraminidase between human influenza A (H1N1) virus and highly pathogenic avian influenza A (H5N1) virus
Lu X , Liu F , Zeng H , Sheu T , Achenbach JE , Veguilla V , Gubareva LV , Garten R , Smith C , Yang H , Stevens J , Xu X , Katz JM , Tumpey TM . Virology 2014 454-455 (1) 169-175 To determine the genetic and antigenic relatedness as well as the cross-protective immunity of human H1N1 and avian H5N1 influenza virus neuraminidase (NA), we immunized rabbits with either a baculovirus-expressed recombinant NA from A/Beijing/262/95 (BJ/262) H1N1 or A/Hong Kong/483/97 (HK/483) H5N1 virus. Cross-reactive antibody responses were evaluated by multiple serological assays and cross-protection against H5N1 virus challenge was evaluated in mice. In a neuraminidase inhibition (NI) test, the antisera exhibited substantial inhibition of NA activity of the homologous virus, but failed to inhibit the NA activity of heterologous virus. However, these antisera exhibited low levels of cross-reactivity measured by plaque size reduction, replication inhibition, single radial hemolysis, and ELISA assays. Passive immunization with HK/483 NA-specific antisera significantly reduced virus replication and disease, and afforded almost complete protection against lethal homologous virus challenge in mice. However, passive immunization with BJ/262 (H1N1) NA-specific antisera was ineffective at providing cross-protection against lethal H5N1 virus challenge and only slightly reduced weight loss. Substantial amino acid variation among the NA antigenic sites was observed between BJ/262 and HK/483 virus, which was consistent with the lack of cross-reactive NI activity by the antibody and limited cross-protective immunity in mice. These results show a strong correlation between the lack of cross-protective immunity and low structural similarities of NA from a human seasonal H1N1 virus and an avian H5N1 influenza virus. |
116E rotavirus vaccine development: a successful alliance
Madhi SA , Parashar UD . Lancet 2014 383 (9935) 2106-7 In The Lancet, Nita Bhandari and colleagues’ study1 about the efficacy of the new 116E rotavirus vaccine in Indian infants offers an opportunity to address the substantial lag in translation of scientific progress for the benefit of the world’s most vulnerable population. Vaccination is considered to be second only to access to potable water in its potential cost-effectiveness as a health-care strategy for improving child health. Most childhood deaths from vaccine-preventable diseases, such as Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, and rotavirus, happen in low-income countries.2 However, introduction of lifesaving vaccines, such as Hib conjugate vaccine, into national immunisation programmes in low-income countries has lagged by as much as 20 years behind implementation in high-income settings.3 Of the many factors responsible, constraints around vaccine affordability and supply are key. | In the past decade, progress has been made in reducing the delay in the introduction of new childhood vaccines (eg, those against pneumococcus and rotavirus) into immunisation programmes between developed and developing countries. This progress is largely attributable to international donor funding coordinated under the auspices of the GAVI Alliance, which among other things provides cofinancing for vaccine procurement at discounted prices negotiated with manufacturers for countries that meet an income threshold for eligibility (presently a gross national income per person of =US$1550). However, the sustainability of the GAVI process, in which countries are expected to take over ownership of funding for vaccine procurement once their gross national income per person exceeds GAVI’s eligibility threshold, remains a concern. One way to address this challenge is to explore approaches to development of low-cost, safe, and effective vaccines that are affordable for low-income countries. | |
Combined use of inactivated and oral poliovirus vaccines in refugee camps and surrounding communities - Kenya, December 2013
Sheikh MA , Makokha F , Hussein AM , Mohamed G , Mach O , Humayun K , Okiror S , Abrar L , Nasibov O , Burton J , Unshur A , Wannemuehler K , Estivariz CF . MMWR Morb Mortal Wkly Rep 2014 63 (11) 237-41 Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988, circulation of indigenous wild poliovirus (WPV) has continued without interruption in only three countries: Afghanistan, Nigeria, and Pakistan. During April-December 2013, a polio outbreak caused by WPV type 1 (WPV1) of Nigerian origin resulted in 217 cases in or near the Horn of Africa, including 194 cases in Somalia, 14 cases in Kenya, and nine cases in Ethiopia (all cases were reported as of March 10, 2014). During December 14-18, 2013, Kenya conducted the first-ever campaign providing inactivated poliovirus vaccine (IPV) together with oral poliovirus vaccine (OPV) as part of its outbreak response. The campaign targeted 126,000 children aged ≤59 months who resided in Somali refugee camps and surrounding communities near the Kenya-Somalia border, where most WPV1 cases had been reported, with the aim of increasing population immunity levels to ensure interruption of any residual WPV transmission and prevent spread from potential new importations. A campaign evaluation and vaccination coverage survey demonstrated that combined administration of IPV and OPV in a mass campaign is feasible and can achieve coverage >90%, although combined IPV and OPV campaigns come at a higher cost than OPV-only campaigns and require particular attention to vaccinator training and supervision. Future operational studies could assess the impact on population immunity and the cost-effectiveness of combined IPV and OPV campaigns to accelerate interruption of poliovirus transmission during polio outbreaks and in certain areas in which WPV circulation is endemic. |
Clinical benefits of electronic health record use: national findings
King J , Patel V , Jamoom EW , Furukawa MF . Health Serv Res 2014 49 392-404 OBJECTIVE: To assess whether physicians' reported electronic health record (EHR) use provides clinical benefits and whether benefits depend on using an EHR meeting Meaningful Use criteria or length of EHR experience. DATA SOURCE: The 2011 Physician Workflow study, representative of U.S. office-based physicians. STUDY DESIGN: Cross-sectional data were used to examine the association of EHR use with enhanced patient care overall and nine specific clinical benefits. PRINCIPAL FINDINGS: Most physicians with EHRs reported EHR use enhanced patient care overall (78 percent), helped them access a patient's chart remotely (81 percent), and alerted them to a potential medication error (65 percent) and critical lab values (62 percent). Between 30 and 50 percent of physicians reported that EHR use was associated with clinical benefits related to providing recommended care, ordering appropriate tests, and facilitating patient communication. Using EHRs that met Meaningful Use criteria and having 2 or more years of EHR experience were independently associated with reported benefits. Physicians with EHRs meeting Meaningful Use criteria and longer EHR experience were most likely to report benefits across all 10 measures. CONCLUSIONS: Physicians reported EHR use enhanced patient care overall. Clinical benefits were most likely to be reported by physicians using EHRs meeting Meaningful Use criteria and longer EHR experience. |
Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID): an extension of the STROBE statement.
Field N , Cohen T , Struelens MJ , Palm D , Cookson B , Glynn JR , Gallo V , Ramsay M , Sonnenberg P , Maccannell D , Charlett A , Egger M , Green J , Vineis P , Abubakar I . Lancet Infect Dis 2014 14 (4) 341-52 Molecular data are now widely used in epidemiological studies to investigate the transmission, distribution, biology, and diversity of pathogens. Our objective was to establish recommendations to support good scientific reporting of molecular epidemiological studies to encourage authors to consider specific threats to valid inference. The statement Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID) builds upon the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative. The STROME-ID statement was developed by a working group of epidemiologists, statisticians, bioinformaticians, virologists, and microbiologists with expertise in control of infection and communicable diseases. The statement focuses on issues relating to the reporting of epidemiological studies of infectious diseases using molecular data that were not addressed by STROBE. STROME-ID addresses terminology, measures of genetic diversity within pathogen populations, laboratory methods, sample collection, use of molecular markers, molecular clocks, timeframe, multiple-strain infections, non-independence of infectious-disease data, missing data, ascertainment bias, consistency between molecular and epidemiological data, and ethical considerations with respect to infectious-disease research. In total, 20 items were added to the 22 item STROBE checklist. When used, the STROME-ID recommendations should advance the quality and transparency of scientific reporting, with clear benefits for evidence reviews and health-policy decision making. |
Characterization of reverse genetics-derived cold-adapted master donor virus A/Leningrad/134/17/57 (H2N2) and reassortants with H5N1 surface genes in a mouse model.
Isakova-Sivak I , Chen LM , Bourgeois M , Matsuoka Y , Voeten JT , Heldens JG , van den Bosch H , Klimov A , Rudenko L , Cox NJ , Donis RO . Clin Vaccine Immunol 2014 21 (5) 722-31 Live attenuated influenza vaccines offer significant advantages over subunit or split inactivated vaccines to mitigate an eventual influenza pandemic, including simpler manufacturing process and more cross-protective immune responses. Using an established reverse genetics (rg) system for wild type A/Leningrad/134/1957 and cold-adapted (ca) A/Leningrad/134/17/1957 (Len17) master donor virus (MDV) we produced and characterized three rg H5N1 reassortant viruses carrying modified HA and intact NA genes from either A/Vietnam/1203/2004 (H5N1, VN1203, clade 1) or A/Egypt/321/2007 (H5N1, EG321, clade 2) viruses. A mouse model of infection was used to determine the infectivity and tissue tropism of the parent wt viruses as compared to the ca master donor viruses as well as the H5N1 resassortants. All ca viruses showed reduced replication in lungs and enhanced replication in nasal epithelium. In addition, the H5N1 HA and NA enhanced replication in lungs unless it was restricted by the internal genes of the ca MDV. Mice inoculated twice four weeks apart with the H5N1 reassortant LAIV candidate viruses developed serum HI and IgA antibody titers to the homologous and heterologous viruses consistent with protective immunity. These animals remained healthy after challenge inoculation with a lethal dose with homologous or heterologous wt H5N1 HPAI. The profiles of viral replication in respiratory tissues, immunogenicity and protective efficacy characteristics of the two ca H5N1 candidate LAIV warrant further development into a vaccine for human use. |
Real-time PCR assays for detection of Brucella spp. and the identification of genotype ST27 in bottlenose dolphins (Tursiops truncatus).
Wu Q , McFee WE , Goldstein T , Tiller RV , Schwacke L . J Microbiol Methods 2014 100 99-104 Rapid detection of Brucella spp. in marine mammals is challenging. Microbiologic culture is used for definitive diagnosis of brucellosis, but is time consuming, has low sensitivity and can be hazardous to laboratory personnel. Serological methods can aid in diagnosis, but may not differentiate prior exposure versus current active infection and may cross-react with unrelated gram-negative bacteria. This study reports a real-time PCR assay for the detection of Brucella spp. and application to screen clinical samples from bottlenose dolphins stranded along the coast of South Carolina, USA. The assay was found to be 100% sensitive for the Brucella strains tested, and the limit of detection was 0.27fg of genomic DNA from B. ceti B1/94 per PCR volume. No amplification was detected for the non-Brucella pathogens tested. Brucella DNA was detected in 31% (55/178) of clinical samples tested. These studies indicate that the real-time PCR assay is highly sensitive and specific for the detection of Brucella spp. in bottlenose dolphins. We also developed a second real-time PCR assay for rapid identification of Brucella ST27, a genotype that is associated with human zoonotic infection. Positive results were obtained for Brucella strains which had been identified as ST27 by multilocus sequence typing. No amplification was found for other Brucella strains included in this study. ST27 was identified in 33% (18/54) of Brucella spp. DNA-positive clinical samples. To our knowledge, this is the first report on the use of a real-time PCR assay for identification of Brucella genotype ST27 in marine mammals. |
Concordance between molecular and phenotypic testing of Mycobacterium tuberculosis complex isolates for resistance to rifampin and isoniazid in the United States.
Yakrus MA , Driscoll J , Lentz AJ , Sikes D , Hartline D , Metchock B , Starks AM . J Clin Microbiol 2014 52 (6) 1932-7 Multidrug-resistant (MDR) isolates of Mycobacterium tuberculosis complex (MTBC) are defined by resistance to at least rifampin (RMP) and isoniazid (INH). Rapid and accurate detection of multidrug resistance is essential for effective treatment and interruption of disease transmission of tuberculosis (TB). Over-diagnosis of MDR TB may result in treatment with second-line drugs that are more costly, less effective, and more poorly tolerated than first-line drugs. CDC offers rapid confirmation of MDR TB by molecular detection of mutations associated with resistance (MDDR) to RMP and INH along with analysis for resistance to other first-line and second-line drugs. Simultaneously, CDC does growth-based phenotypic drug susceptibility testing (DST) by the indirect agar proportion method for a panel of first-line and second-line antituberculous drugs. We reviewed discordance between molecular and phenotypic DST for INH and RMP for 285 isolates submitted as MTBC to CDC September 2009-February 2011. We compared CDC's results with those from the submitting public health laboratories (PHL). Concordance between molecular and phenotypic testing at CDC was 97.4% for RMP and 92.5% for INH resistance. Concordance between CDC's molecular testing and PHL DST results was 93.9% for RMP and 90.0% for INH. Overall concordance between CDC molecular and PHL DST results was 91.7% for RMP and INH collectively. Discordance was primarily attributable to absence of known INH-resistance mutations in isolates INH resistant by DST and detection of mutations associated with low-level RMP resistance in isolates that were RMP susceptible by phenotypic DST. Both molecular and phenotypic test results should be considered for diagnosis of MDR TB. |
Quantitation of five organophosphorus nerve agent metabolites in serum using hydrophilic interaction liquid chromatography and tandem mass spectrometry
Hamelin EI , Schulze ND , Shaner RL , Coleman RM , Lawrence RJ , Crow BS , Jakubowski EM , Johnson RC . Anal Bioanal Chem 2014 406 (21) 5195-202 Although nerve agent use is prohibited, concerns remain for human exposure to nerve agents during decommissioning, research, and warfare. Exposure can be detected through the analysis of hydrolysis products in urine as well as blood. An analytical method to detect exposure to five nerve agents, including VX, VR (Russian VX), GB (sarin), GD (soman), and GF (cyclosarin), through the analysis of the hydrolysis products, which are the primary metabolites, in serum has been developed and characterized. This method uses solid-phase extraction coupled with high-performance liquid chromatography for separation and isotopic dilution tandem mass spectrometry for detection. An uncommon buffer of ammonium fluoride was used to enhance ionization and improve sensitivity when coupled with hydrophilic interaction liquid chromatography resulting in detection limits from 0.3 to 0.5 ng/mL. The assessment of two quality control samples demonstrated high accuracy (101-105 %) and high precision (5-8 %) for the detection of these five nerve agent hydrolysis products in serum. |
Fluoroquinolone susceptibility testing of Salmonella enterica: detection of acquired resistance and selection of zone diameter breakpoints for levofloxacin and ofloxacin
Sjolund-Karlsson M , Howie RL , Crump JA , Whichard JM . J Clin Microbiol 2014 52 (3) 877-84 Fluoroquinolones (e.g., ciprofloxacin) have become a mainstay for treating severe Salmonella infections in adults. Fluoroquinolone resistance in Salmonella is mostly due to mutations in the topoisomerase genes, but plasmid-mediated quinolone resistance (PMQR) mechanisms have also been described. In 2012, the Clinical and Laboratory Standards Institute (CLSI) revised the ciprofloxacin interpretive criteria (breakpoints) for disk diffusion and MIC test methods for Salmonella. In 2013, the CLSI published MIC breakpoints for Salmonella to levofloxacin and ofloxacin, but breakpoints for assigning disk diffusion results to susceptible (S), intermediate (I), and resistant (R) categories are still needed. In this study, the MICs and inhibition zone diameters for nalidixic acid, ciprofloxacin, levofloxacin, and ofloxacin were determined for 100 clinical isolates of nontyphi Salmonella with or without resistance mechanisms. We confirmed that the new levofloxacin MIC breakpoints resulted in the highest category agreement (94%) when plotted against the ciprofloxacin MICs and that the new ofloxacin MIC breakpoints resulted in 92% category agreement between ofloxacin and ciprofloxacin. By applying the new MIC breakpoints in the MIC zone scattergrams for levofloxacin and ofloxacin, the following disk diffusion breakpoints generated the least number of errors: ≥28 mm (S), 19 to 27 mm (I), and ≤18 mm (R) for levofloxacin and ≥25 mm (S), 16 to 24 mm (I), and ≤15 mm (R) for ofloxacin. Neither the levofloxacin nor the ofloxacin disk yielded good separation of isolates with and without resistance mechanisms. Further studies will be needed to develop a disk diffusion assay that efficiently detects all isolates with acquired resistance to fluoroquinolones. |
Advances in mechanisms of anti-oxidation
Ma Q . Discov Med 2014 17 (93) 121-30 Reactive oxygen species (ROS) are a family of molecules that are continuously produced from oxygen consumption in aerobic cells. Controlled generation of ROS in normal cells serves useful purposes to regulate important cellular processes such as cell proliferation, inflammation, and immune response, but overproduction of ROS causes oxidative stress that contributes to the development of cancer, chronic disease, and aging. These hugely different consequences of ROS exposure demand a carefully balanced control of ROS production and disposition, which is largely achieved through the body's elaborate antioxidant system. The human antioxidant system consists of small antioxidants, antioxidant proteins, ROS-metabolizing enzymes, as well as many regulator proteins that mediate adaptive responses to oxidant stress. How such a complex system reacts with oxidants and achieves the required specificity and sensitivity for proper anti-oxidation is incompletely understood. In this respect, new advances in the understanding of the chemistry that determines the reaction of a given oxidant or antioxidant with a protein target provide considerable insights into these and related questions. The findings hold certain promise for new drug development for preventing and treating diseases associated with oxidant tissue damage. |
Aptamer-based proteomic signature of intensive phase treatment response in pulmonary tuberculosis
Nahid P , Bliven-Sizemore E , Jarlsberg LG , De Groote MA , Johnson JL , Muzanyi G , Engle M , Weiner M , Janjic N , Sterling DG , Ochsner UA . Tuberculosis (Edinb) 2014 94 (3) 187-96 BACKGROUND: New drug regimens of greater efficacy and shorter duration are needed for tuberculosis (TB) treatment. The identification of accurate, quantitative, non-culture based markers of treatment response would improve the efficiency of Phase 2 TB drug testing. METHODS: In an unbiased biomarker discovery approach, we applied a highly multiplexed, aptamer-based, proteomic technology to analyze serum samples collected at baseline and after 8 weeks of treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in a Centers for Disease Control and Prevention (CDC) TB Trials Consortium Phase 2B treatment trial. RESULTS: We identified protein expression differences associated with 8-week culture status, including Coagulation Factor V, SAA, XPNPEP1, PSME1, IL-11 Ralpha, HSP70, Galectin-8, alpha2-Antiplasmin, ECM1, YES, IGFBP-1, CATZ, BGN, LYNB, and IL-7. Markers noted to have differential changes between responders and slow-responders included nectin-like protein 2, EphA1 (Ephrin type-A receptor 1), gp130, CNDP1, TGF-b RIII, MRC2, ADAM9, and CDON. A logistic regression model combining markers associated with 8-week culture status revealed an ROC curve with AUC = 0.96, sensitivity = 0.95 and specificity = 0.90. Additional markers showed differential changes between responders and slow-responders (nectin-like protein), or correlated with time-to-culture-conversion (KLRK1). CONCLUSIONS: Serum proteins involved in the coagulation cascade, neutrophil activity, immunity, inflammation, and tissue remodeling were found to be associated with TB treatment response. A quantitative, non-culture based, five-marker signature predictive of 8-week culture status was identified in this pilot study. |
Certification of total arsenic in blood and urine standard reference materials by radiochemical neutron activation analysis and inductively coupled plasma-mass spectrometry
Paul RL , Davis WC , Yu L , Murphy KE , Guthrie WF , Leber DD , Bryan CE , Vetter TW , Shakirova G , Mitchell G , Kyle DJ , Jarrett JM , Caldwell KL , Jones RL , Eckdahl S , Wermers M , Maras M , Palmer CD , Verostek MF , Geraghty CM , Steuerwald AJ , Parsons PJ . J Radioanal Nucl Chem 2014 299 (3) 1555-1563 Radiochemical neutron activation analysis (RNAA) was used to measure arsenic at four levels in standard reference material (SRM) 955c Toxic Elements in Caprine Blood and at two levels in SRM 2668 Toxic Elements in Frozen Human Urine for the purpose of providing mass concentration values for certification. Samples were freeze-dried prior to analysis followed by neutron irradiation for 3 h at a fluence rate of 1 × 10^14 cm^−2 s^−1. After sample dissolution in perchloric and nitric acids, arsenic was separated from the matrix either by retention on hydrated manganese dioxide (urine) or by extraction into zinc diethyldithiocarbamate in chloroform (blood). ^76As was quantified by gamma-ray spectroscopy. Differences in chemical yield and counting geometry between samples and standards were monitored by measuring the count rate of a ^77As tracer added before sample dissolution. RNAA results were combined with inductively coupled plasma-mass spectrometry values from National Institute of Standards and Technology and collaborating laboratories to provide certified values of 10.81 ± 0.54 and 213.1 ± 0.73 μg/L for SRM 2668 Levels I and II, and certified values of 21.66 ± 0.73, 52.7 ± 1.1, and 78.8 ± 4.9 μg/L for SRM 955c Levels II–IV, respectively. Because of discrepancies between values obtained by different methods for SRM 955c Level I, an information value of <5 μg/L was assigned for this material. |
Comparison of creatinine and specific gravity for hydration corrections on measurement of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine
Xia Y , Wong LY , Bunker BC , Bernert JT . J Clin Lab Anal 2014 28 (5) 353-63 BACKGROUND: Tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was measured in all participants aged 6 years and older from the Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey 2007-2008. The suitability of using creatinine or specific gravity for urinary NNAL correction in exposure assessment is examined in this study. METHODS: Effects of both specific gravity and creatinine correction on urinary NNAL among smokers were investigated with multiple linear regression models using either normalization or the fitting of creatinine and specific gravity in the model as covariates. RESULTS: When log-scaled NNAL was normalized by either creatinine or specific gravity, R2 was slightly higher for creatinine than for specific gravity (R2 = 0.1694 and 0.1439, for creatinine and specific gravity, respectively). When log-scaled NNAL was normalized by both factors, the R2 was improved (R2 = 0.2068). When specific gravity or creatinine was included as a covariate separately in the models, they were highly significant factors (P < 0.001, R2 = 0.2226 and 0.1681 for creatinine and specific gravity, respectively). However, when both were included in the model as covariates, creatinine remained highly significant (P < 0.001), whereas the significance of specific gravity was eliminated (P = 0.4294). CONCLUSION: This study confirms significant relationships between NNAL concentrations and both urine creatinine and specific gravity. We conclude that creatinine is the more influential and preferred variable to account for urine dilution in tobacco-specific nitrosamine exposure assessment. |
Development of a prototype lateral flow immunoassay (LFI) for the rapid diagnosis of melioidosis
Houghton RL , Reed DE , Hubbard MA , Dillon MJ , Chen H , Currie BJ , Mayo M , Sarovich DS , Theobald V , Limmathurotsakul D , Wongsuvan G , Chantratita N , Peacock SJ , Hoffmaster AR , Duval B , Brett PJ , Burtnick MN , Aucoin DP . PLoS Negl Trop Dis 2014 8 (3) e2727 Burkholderia pseudomallei is a soil-dwelling bacterium and the causative agent of melioidosis. Isolation of B. pseudomallei from clinical samples is the "gold standard" for the diagnosis of melioidosis; results can take 3-7 days to produce. Alternatively, antibody-based tests have low specificity due to a high percentage of seropositive individuals in endemic areas. There is a clear need to develop a rapid point-of-care antigen detection assay for the diagnosis of melioidosis. Previously, we employed In vivo Microbial Antigen Discovery (InMAD) to identify potential B. pseudomallei diagnostic biomarkers. The B. pseudomallei capsular polysaccharide (CPS) and numerous protein antigens were identified as potential candidates. Here, we describe the development of a diagnostic immunoassay based on the detection of CPS. Following production of a CPS-specific monoclonal antibody (mAb), an antigen-capture immunoassay was developed to determine the concentration of CPS within a panel of melioidosis patient serum and urine samples. The same mAb was used to produce a prototype Active Melioidosis Detect Lateral Flow Immunoassay (AMD LFI); the limit of detection of the LFI for CPS is comparable to the antigen-capture immunoassay ( approximately 0.2 ng/ml). The analytical reactivity (inclusivity) of the AMD LFI was 98.7% (76/77) when tested against a large panel of B. pseudomallei isolates. Analytical specificity (cross-reactivity) testing determined that 97.2% of B. pseudomallei near neighbor species (35/36) were not reactive. The non-reactive B. pseudomallei strain and the reactive near neighbor strain can be explained through genetic sequence analysis. Importantly, we show the AMD LFI is capable of detecting CPS in a variety of patient samples. The LFI is currently being evaluated in Thailand and Australia; the focus is to optimize and validate testing procedures on melioidosis patient samples prior to initiation of a large, multisite pre-clinical evaluation. |
Systematic review of the birth prevalence of congenital cytomegalovirus infection in developing countries
Lanzieri TM , Dollard SC , Bialek SR , Grosse SD . Int J Infect Dis 2014 22 44-8 BACKGROUND: Congenital cytomegalovirus (CMV) infection is the leading infectious cause of congenital hearing loss and neurodevelopmental disability in developed countries. Information on congenital CMV infection in developing countries appears to be lacking. METHODS: We conducted a systematic literature review to identify studies from developing countries with population-based samples of at least 300 infants that used laboratory methods established as reliable for the diagnosis of congenital CMV infection. RESULTS: Most studies were excluded due to biased samples or inadequate diagnostic methods; consequently the search identified just 11 studies that were from Africa, Asia, and Latin America. The number of newborns tested ranged from 317 to 12 195. Maternal CMV seroprevalence ranged from 84% to 100%. CMV birth prevalence varied from 0.6% to 6.1%. CMV-associated impairments were not documented in most studies. CONCLUSIONS: Birth prevalence ranges were higher than for Europe and North America, as expected based on the higher maternal CMV seroprevalence. With very limited data available on sequelae, the disease burden of congenital CMV in developing countries remains largely unknown at this time. |
Nutritional status of young children with inherited blood disorders in western Kenya
Tsang BL , Sullivan KM , Ruth LJ , Williams TN , Suchdev PS . Am J Trop Med Hyg 2014 90 (5) 955-962 To determine the association between a range of inherited blood disorders and indicators of poor nutrition, we analyzed data from a population-based, cross-sectional survey of 882 children 6-35 months of age in western Kenya. Of children with valid measurements, 71.7% were anemic (hemoglobin < 11 g/dL), 19.1% had ferritin levels < 12 mug/L, and 30.9% had retinol binding protein (RBP) levels < 0.7 mumol/L. Unadjusted analyses showed that compared with normal children, alpha+-thalassemia trait individuals had a higher prevalence of anemia (82.3% versus 66.8%, P = 0.001), but a lower prevalence of low RBP (20.5% versus 31.4%, P = 0.024). In multivariable analysis, alpha+-thalassemia trait remained associated with anemia (adjusted odds ratio [aOR] = 1.8, P = 0.004) but not with low RBP (aOR = 0.6, P = 0.065). Among young Kenyan children, alpha+-thalassemia is associated with anemia, whereas G6PD deficiency, haptoglobin 2-2, and HbS are not; none of these blood disorders are associated with iron deficiency, vitamin A deficiency, or poor growth. |
Vibration induced white-feet: overview and field study of vibration exposure and reported symptoms in workers
Eger T , Thompson A , Leduc M , Krajnak K , Groggins K , Goodwin A , House R . Work 2014 47 (1) 101-110 BACKGROUND: Workers who stand on platforms or equipment that vibrate are exposed to foot-transmitted vibration (FTV). Exposure to FTV can lead to vibration white feet/toes resulting in blanching of the toes, and tingling and numbness in the feet and toes. OBJECTIVES: The objectives are 1) to review the current state of knowledge of the health risks associated with foot-transmitted vibration (FTV), and 2) to identify the characteristics of FTV and discuss the associated risk of vibration-induced injury. PARTICIPANTS: Workers who operated locomotives (n = 3), bolting platforms (n = 10), jumbo drills (n = 7), raise drilling platforms (n = 4), and crushers (n = 3), participated. METHODS: A tri-axial accelerometer was used to measure FTV in accordance with ISO 2631-1 guidelines. Frequency-weighted root-mean-square acceleration and the dominant frequency are reported. Participants were also asked to report pain/ache/discomfort in the hands and/or feet. RESULTS: Reports of pain/discomfort/ache were highest in raise platform workers and jumbo drill operators who were exposed to FTV in the 40 Hz and 28 Hz range respectively. Reports of discomfort/ache/pain were lowest in the locomotive and crusher operators who were exposed to FTV below 10 Hz. These findings are consistent with animal studies that have shown vascular and neural damage in exposed appendages occurs at frequencies above 40 Hz. CONCLUSIONS: Operators exposed to FTV at 40 Hz appear to be at greater risk of experiencing vibration induced injury. Future research is required to document the characteristics of FTV and epidemiological evidence is required to link exposure with injury. |
Workplace hazards and prevention options from a nonrandom sample of retail trade businesses
Anderson VP , Chun H . Int J Occup Saf Ergon 2014 20 (1) 181-95 Employer commitment is a key factor in an effective safety program, yet limited research has focused on the safety priorities of retail store managers. To address this, the U.S. National Institute for Occupational Safety and Health recruited 4 experienced ergonomists, who met and interviewed 9 retailers in different parts of the eastern USA. The reports from the 9 interviews were used to document the hazards facing retailers and the interventions they attempted. Those interviewed were managers/owners of establishments that ranged from a small bakery with 11 employees to a supermarket with 85 or more employees. The main hazards across all establishments included overexertion, contact-with-objects, and falls-to-the-same-level. We also compared the retailers' perceptions of safety hazards with injuries from actual hazards as supplied by the U.S. Bureau of Labor Statistics. This report provides insight into the retailers' perceptions of safety hazards as well as their commitment to the prevention of workplace injuries. |
Methods and feasibility of collecting occupational data for a large population-based cohort study in the United States: the reasons for geographic and racial differences in stroke study
MacDonald LA , Pulley L , Hein MJ , Howard VJ . BMC Public Health 2014 14 (1) 142 BACKGROUND: Coronary heart disease and stroke are major contributors to preventable mortality. Evidence links work conditions to these diseases; however, occupational data are perceived to be difficult to collect for large population-based cohorts. We report methodological details and the feasibility of conducting an occupational ancillary study for a large U.S. prospective cohort being followed longitudinally for cardiovascular disease and stroke. METHODS: Current and historical occupational information were collected from active participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study. A survey was designed to gather quality occupational data among this national cohort of black and white men and women aged 45 years and older (enrolled 2003-2007). Trained staff conducted Computer-Assisted Telephone Interviews (CATI). After a brief pilot period, interviewers received additional training in the collection of narrative industry and occupation data before administering the survey to remaining cohort members. Trained coders used a computer-assisted coding system to assign U.S. Census codes for industry and occupation. All data were double coded; discrepant codes were independently resolved. RESULTS: Over a 2-year period, 17,648 participants provided consent and completed the occupational survey (87% response rate). A total of 20,427 jobs were assigned Census codes. Inter-rater reliability was 80% for industry and 74% for occupation. Less than 0.5% of the industry and occupation data were uncodable, compared with 12% during the pilot period. Concordance between the current and longest-held jobs was moderately high. The median time to collect employment status plus narrative and descriptive job information by CATI was 1.6 to 2.3 minutes per job. Median time to assign Census codes was 1.3 minutes per rater. CONCLUSIONS: The feasibility of conducting high-quality occupational data collection and coding for a large heterogeneous population-based sample was demonstrated. We found that training for interview staff was important in ensuring that narrative responses for industry and occupation were adequately specified for coding. Estimates of survey administration time and coding from digital records provide an objective basis for planning future studies. The social and environmental conditions of work are important understudied risk factors that can be feasibly integrated into large population-based health studies. |
Psychophysical basis for maximum pushing and pulling forces: a review and recommendations
Garg A , Waters T , Kapellusch J , Karwowski W . Int J Ind Ergon 2014 44 (2) 281-291 The objective of this paper was to perform a comprehensive review of psychophysically determined maximum acceptable pushing and pulling forces. Factors affecting pushing and pulling forces are identified and discussed. Recent studies show a significant decrease (compared to previous studies) in maximum acceptable forces for males but not for females when pushing and pulling on a treadmill. A comparison of pushing and pulling forces measured using a high inertia cart with those measured on a treadmill shows that the pushing and pulling forces using high inertia cart are higher for males but are about the same for females. It is concluded that the recommendations of Snook and Ciriello (1991) for pushing and pulling forces are still valid and provide reasonable recommendations for ergonomics practitioners. Regression equations as a function of handle height, frequency of exertion and pushing/pulling distance are provided to estimate maximum initial and sustained forces for pushing and pulling acceptable to 75% male and female workers.At present it is not clear whether pushing or pulling should be favored. Similarly, it is not clear what handle heights would be optimal for pushing and pulling. Epidemiological studies are needed to determine relationships between psychophysically determined maximum acceptable pushing and pulling forces and risk of musculoskeletal injuries, in particular to low back and shoulders. Relevance to industry: This article provides a concise discussion of important factors relevant to designing and analyzing pushing/pulling tasks. Regression equations to estimate initial and sustained pushing and pulling forces acceptable to 75% male and female workers are provided and can be used to design and analyze pushing and pulling tasks common in industry. |
Evaluation of engineering controls for the mixing of flavorings containing diacetyl and other volatile ingredients
Hirst DV , Dunn KH , Shulman SA , Hammond DR , Sestito N . J Occup Environ Hyg 2014 11 (10) 680-7 Exposures to diacetyl, a primary ingredient of butter flavoring, have been shown to cause respiratory disease among workers who mix flavorings. This study focused on evaluating ventilation controls designed to reduce emissions from the flavor mixing tanks, the major source of diacetyl in the plants. Five exhaust hood configurations were evaluated in the laboratory: standard hinged lid-opened, standard hinged lid-closed, hinged lid-slotted, dome with 38-mm gap, and dome with 114-mm gap. Tracer gas tests were performed to evaluate quantitative capture efficiency for each hood. A perforated copper coil was used to simulate an area source within the 1.2-meter diameter mixing tank. Capture efficiencies were measured at four hood exhaust flow rates (2.83, 5.66, 11.3, and 17.0 cubic meters per minute) and three cross draft velocities (0, 30, and 60 meters per minute). All hoods evaluated performed well with capture efficiencies above 90% for most combinations of exhaust volume and cross drafts. The standard hinged lid was the least expensive to manufacture and had the best average capture efficiency (over 99%) in the closed configuration for all exhaust flow rates and cross drafts. The hinged lid-slotted hood had some of the lowest capture efficiencies at the low exhaust flow rates compared to the other hood designs. The standard hinged lid performed well, even in the open position, and it provided a flexible approach to controlling emissions from mixing tanks. The dome hood gave results comparable to the standard hinged lid but it is more expensive to manufacture. The results of the study indicate that emissions from mixing tanks used in the production of flavorings can be controlled using simple inexpensive exhaust hoods. |
Fleet safety: developing & sustaining an effective program with ANSI/ASSE Z15.1
Hammer BS , Pratt SG , Ross P . Prof Saf 2014 59 (3) 47-56 The risk of work-related motor vehicle crashes cuts across all industries and occupations. Between 2003 and 2008, workers employed by truck transportation companies had the highest risk of work-related fatality due to vehicle crashes while driving or riding in a motor vehicle on a public roadway. This article discusses how ANSI/ASSE Z15.1-2012 provides comprehensive guidance on fleet safety program elements and can be used as a foundation for auditing an existing program. |
Genotoxicity of multi-walled carbon nanotubes at occupationally relevant doses
Siegrist KJ , Reynolds SH , Kashon ML , Lowry DT , Dong C , Hubbs AF , Young SH , Salisbury JL , Porter DW , Benkovic SA , McCawley M , Keane MJ , Mastovich JT , Bunker KL , Cena LG , Sparrow MC , Sturgeon JL , Dinu CZ , Sargent LM . Part Fibre Toxicol 2014 11 6 Carbon nanotubes are commercially-important products of nanotechnology; however, their low density and small size makes carbon nanotube respiratory exposures likely during their production or processing. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to single-walled carbon nanotubes (SWCNT). In this study, we examined whether multi-walled carbon nanotubes (MWCNT) cause mitotic spindle damage in cultured cells at doses equivalent to 34 years of exposure at the NIOSH Recommended Exposure Limit (REL). MWCNT induced a dose responsive increase in disrupted centrosomes, abnormal mitotic spindles and aneuploid chromosome number 24 hours after exposure to 0.024, 0.24, 2.4 and 24 mug/cm(2) MWCNT. Monopolar mitotic spindles comprised 95% of disrupted mitoses. Three-dimensional reconstructions of 0.1 mum optical sections showed carbon nanotubes integrated with microtubules, DNA and within the centrosome structure. Cell cycle analysis demonstrated a greater number of cells in S-phase and fewer cells in the G2 phase in MWCNT-treated compared to diluent control, indicating a G1/S block in the cell cycle. The monopolar phenotype of the disrupted mitotic spindles and the G1/S block in the cell cycle is in sharp contrast to the multi-polar spindle and G2 block in the cell cycle previously observed following exposure to SWCNT. One month following exposure to MWCNT there was a dramatic increase in both size and number of colonies compared to diluent control cultures, indicating a potential to pass the genetic damage to daughter cells. Our results demonstrate significant disruption of the mitotic spindle by MWCNT at occupationally relevant exposure levels. |
Health risks, travel preparation, and illness among public health professionals during international travel
Balaban V , Warnock E , Ramana Dhara V , Jean-Louis LA , Sotir MJ , Kozarsky P . Travel Med Infect Dis 2014 12 (4) 349-54 BACKGROUND: Few data currently exist on health risks faced by public health professionals (PHP) during international travel. We conducted pre- and post-travel health surveys to assess knowledge, attitudes, and practices (KAP), and illnesses among PHP international travelers. METHOD: Anonymous surveys were completed by PHP from a large American public health agency who sought a pre-travel medical consult from September 1, 2009, to September 30, 2010. RESULTS: Surveys were completed by 122 participants; travelers went to 163 countries. Of the 122 respondents, 97 (80%) reported at least one planned health risk activity (visiting rural areas, handling animals, contact with blood or body fluids, visiting malarious areas), and 50 (41%) reported exposure to unanticipated health risks. Of the 62 travelers who visited malarious areas, 14 (23%) reported inconsistent or no use of malaria prophylaxis. Illness during travel was reported by 33 (27%) respondents. CONCLUSIONS: Most of the PHP travelers in our study reported at least one planned health risk activity, and almost half reported exposure to unanticipated health risks, and one-quarter of travelers to malarious areas reported inconsistent or no use of malaria chemoprophylaxis. Our findings highlight that communication and education outreach for PHP to prevent travel-associated illnesses can be improved. |
Interventions to prevent occupational noise-induced hearing loss: a Cochrane systematic review
Verbeek JH , Kateman E , Morata TC , Dreschler WA , Mischke C . Int J Audiol 2014 53 Suppl 2 S84-96 OBJECTIVE: To assess the effectiveness of interventions for preventing occupational noise exposure or hearing loss compared to no intervention or alternative interventions. DESIGN: We searched biomedical databases up to 25 January 2012 for randomized controlled trials (RCT), controlled before-after studies and interrupted time-series of hearing loss prevention among workers exposed to noise. STUDY SAMPLE: We included 19 studies with 82 794 participants evaluating effects of hearing loss prevention programs (HLPP). The overall quality of studies was low to very low, as rated using the GRADE approach. RESULTS: One study of stricter legislation showed a favorable effect on noise levels. Three studies, of which two RCTs, did not find an effect of a HLPP. Four studies showed that better use of hearing protection devices in HLPPs decreased the risk of hearing loss. In four other studies, workers in a HLPP still had a 0.5 dB greater hearing loss at 4 kHz (95% CI - 0.5 to 1.7) than non-exposed workers. In two similar studies there was a substantial risk of hearing loss in spite of a HLPP. CONCLUSIONS: Stricter enforcement of legislation and better implementation of HLPPs can reduce noise levels in workplaces. Better evaluations of technical interventions and long-term effects are needed. |
Chemotherapy: biomarkers of exposure, effect, reproductive hazards, and cancer
Roussel C , Connor TH . Oncol Pharm 2014 7 (1) 1,10-13,18 This article discusses approaches that have been used to examine potentially adverse outcomes in healthcare professionals who work with or are exposed to chemotherapy drugs: (1) the use of biomarkers to evaluate genotoxic damage; (2) adverse reproductive outcomes; and (3) the association of cancer with exposure to chemotherapy drugs. Biomarkers of exposure and effect have been used extensively to monitor both healthcare professionals who work with antineoplastic(3-5) and other hazardous drugs, and workers in other occupational settings who may be exposed to genotoxic chemicals. In general, biomarkers are based on mutagenic or other end points of genotoxicity of the drugs. As most of the first generation of antineoplastic drugs were genotoxic in one test system or another, they were ideal candidates for use in exposed worker populations. However, these end points are typically nonspecific in nature and can result from exposure to any genotoxic compound, certain types of radiation, and possibly viral infections. Therefore, studies of worker populations must be carefully designed to rule out extraneous factors such as smoking history, diet, age, and other variables that may compromise test results. Nevertheless, more than half of the 100-plus published studies in the literature have reported a statistically significant association between exposure to antineoplastic drugs and the end point being investigated. Most of these studies have originated outside the United States, and they often have been conducted in countries where safety precautions may not be as rigorous as in the United States. |
Considerations for recommending extended use and limited reuse of filtering facepiece respirators in healthcare settings
Fisher EM , Shaffer RE . J Occup Environ Hyg 2014 11 (8) D115-28 Public health organizations, such as the Centers for Disease Control and Prevention (CDC), are increasingly recommending the use of N95 filtering facepiece respirators (FFRs) in healthcare settings. For infection control purposes, the usual practice is to discard FFRs after close contact with a patient ("single use"). However, in some situations, such as during contact with tuberculosis patients, limited FFR reuse (i.e., repeated donning and doffing of the same FFR by the same person) is practiced. A related practice, extended use, involves wearing the same FFR for multiple patient encounters without doffing. Extended use and limited FFR reuse have been recommended during infectious disease outbreaks and pandemics to conserve FFR supplies. This commentary examines CDC recommendations related to FFR extended use and limited reuse and analyzes available data from the literature to provide a relative estimate of the risks of these practices compared to single use. |
Using mitochondrial genome sequences to track the origin of imported Plasmodium vivax infections diagnosed in the United States.
Rodrigues PT , Alves JM , Santamaria AM , Calzada JE , Xayavong M , Parise M , da Silva AJ , Ferreira MU . Am J Trop Med Hyg 2014 90 (6) 1102-8 Although the geographic origin of malaria cases imported into the United States can often be inferred from travel histories, these histories may be lacking or incomplete. We hypothesized that mitochondrial haplotypes could provide region-specific molecular barcodes for tracing the origin of imported Plasmodium vivax infections. An analysis of 348 mitochondrial genomes from worldwide parasites and new sequences from 69 imported malaria cases diagnosed across the United States allowed for a geographic assignment of most infections originating from the Americas, southeast Asia, east Asia, and Melanesia. However, mitochondrial lineages from Africa, south Asia, central Asia, and the Middle East, which altogether contribute the vast majority of imported malaria cases in the United States, were closely related to each other and could not be reliably assigned to their geographic origins. More mitochondrial genomes are required to characterize molecular barcodes of P. vivax from these regions. |
Patient-, health worker-, and health facility-level determinants of correct malaria case management at publicly funded health facilities in Malawi: results from a nationally representative health facility survey
Steinhardt LC , Chinkhumba J , Wolkon A , Luka M , Luhanga M , Sande J , Oyugi J , Ali D , Mathanga D , Skarbinski J . Malar J 2014 13 (1) 64 BACKGROUND: Prompt and effective case management is needed to reduce malaria morbidity and mortality. However, malaria diagnosis and treatment is a multistep process that remains problematic in many settings, resulting in missed opportunities for effective treatment as well as overtreatment of patients without malaria. METHODS: Prior to the widespread roll-out of malaria rapid diagnostic tests (RDTs) in late 2011, a national, cross-sectional, complex-sample, health facility survey was conducted in Malawi to assess patient-, health worker-, and health facility-level factors associated with malaria case management quality using multivariate Poisson regression models. RESULTS: Among the 2,019 patients surveyed, 34% had confirmed malaria defined as presence of fever and parasitaemia on a reference blood smear. Sixty-seven per cent of patients with confirmed malaria were correctly prescribed the first-line anti-malarial, with most cases of incorrect treatment due to missed diagnosis; 31% of patients without confirmed malaria were overtreated with an anti-malarial. More than one-quarter of patients were not assessed for fever or history of fever by health workers. The most important determinants of correct malaria case management were patient-level clinical symptoms, such as spontaneous complaint of fever to health workers, which increased both correct treatment and overtreatment by 72 and 210%, respectively (p < 0.0001). Complaint of cough was associated with a 27% decreased likelihood of correct malaria treatment (p = 0.001). Lower-level cadres of health workers were more likely to prescribe anti-malarials for patients, increasing the likelihood of both correct treatment and overtreatment, but no other health worker or health facility-level factors were significantly associated with case management quality. CONCLUSIONS: Introduction of RDTs holds potential to improve malaria case management in Malawi, but health workers must systematically assess all patients for fever, and then test and treat accordingly, otherwise, malaria control programmes might miss an opportunity to dramatically improve malaria case management, despite better diagnostic tools. |
Scaling up of physical activity interventions in Brazil: how partnerships and research evidence contributed to policy action
Parra DC , Hoehner CM , Hallal PC , Reis RS , Simoes EJ , Malta DC , Pratt M , Brownson RC . Glob Health Promot 2013 20 (4) 5-12 The global health burden due to physical inactivity is enormous and growing. There is a need to consider new ways of generating evidence and to identify the role of government in promoting physical activity at the population level. In this paper, we summarize key findings from a large-scale cross-national collaboration to understand physical activity promotion in Brazil. We describe the main aspects of the partnership of Project GUIA (Guide for Useful Interventions for Activity in Brazil and Latin America) that sustained the collaborative effort for eight years and describe how the evidence gathered from the collaboration triggered political action in Brazil to scale up a physical activity intervention at the national level. Project GUIA is a cross-national multidisciplinary research partnership designed to understand and evaluate current efforts for physical activity promotion at the community level in Latin America. This example of scaling up is unprecedented for promoting health in the region and is an example that must be followed and evaluated. |
Substance use and drinking outcomes in Personalized Cognitive Counseling randomized trial for episodic substance-using men who have sex with men
Santos GM , Coffin PO , Vittinghoff E , Demicco E , Das M , Matheson T , Raiford JL , Carry M , Colfax G , Herbst JH , Dilley JW . Drug Alcohol Depend 2014 138 234-9 BACKGROUND: Non-dependent alcohol and substance use patterns are prevalent among men who have sex with men (MSM), yet few effective interventions to reduce their substance use are available for these men. We evaluated whether an adapted brief counseling intervention aimed at reducing HIV risk behavior was associated with secondary benefits of reducing substance use among episodic substance-using MSM (SUMSM). METHODS: 326 episodic SUMSM were randomized to brief Personalized Cognitive Counseling (PCC) intervention with rapid HIV testing or to rapid HIV testing only control. Both arms followed over 6 months. Trends in substance use were examined using GEE Poisson models with robust standard errors by arm. Reductions in frequency of use were examined using ordered logistic regression. RESULTS: In intent-to-treat analyses, compared to men who received rapid HIV testing only, we found men randomized to PCC with rapid HIV testing were more likely to report abstaining from alcohol consumption (RR=0.93; 95% CI=0.89-0.97), marijuana use (RR=0.84; 95% CI=0.73-0.98), and erectile dysfunction drug use (EDD; RR=0.51; 95% CI=0.33-0.79) over the 6-month follow-up. PCC was also significantly associated with reductions in frequency of alcohol intoxication (OR=0.58; 95% CI=0.36-0.90) over follow-up. Furthermore, we found PCC was associated with significant reductions in number of unprotected anal intercourse events while under the influence of methamphetamine (RR=0.26; 95% CI=0.08-0.84). CONCLUSION: The addition of adapted PCC to rapid HIV testing may have benefits in increasing abstinence from certain classes of substances previously associated with HIV risk, including alcohol and EDD; and reducing alcohol intoxication frequency and high-risk sexual behaviors concurrent with methamphetamine use. |
Confronting the emerging epidemic of HCV infection among young injection drug users
Valdiserri R , Khalsa J , Dan C , Holmberg S , Zibbell J , Holtzman D , Lubran R , Compton W . Am J Public Health 2014 104 (5) 816-21 Hepatitis C virus infection is a significant public health problem in the United States and an important cause of morbidity and mortality. Recent reports document HCV infection increases among young injection drug users in several US regions, associated with America's prescription opioid abuse epidemic. Incident HCV infection increases among young injectors who have recently transitioned from oral opioid abuse present an important public health challenge requiring a comprehensive, community-based response. We summarize recommendations from a 2013 Office of HIV/AIDS and Infectious Disease Policy convening of experts in epidemiology, behavioral science, drug prevention and treatment, and other research; community service providers; and federal, state, and local government representatives. Their observations highlight gaps in our surveillance, program, and research portfolios and advocate a syndemic approach to this emerging public health problem. |
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