Arthritis restricts volunteer participation: prevalence and correlates of volunteer status among adults with arthritis
Theis KA , Murphy L , Hootman JM , Helmick CG , Sacks JJ . Arthritis Care Res (Hoboken) 2010 62 (7) 907-16 OBJECTIVE: To estimate, among adults ages > or = 45 years with arthritis, the prevalence and correlates of 1) volunteering, 2) arthritis-attributable restrictions among volunteers, and 3) arthritis as the main barrier to volunteering (AMBV) among non-volunteers. METHODS: Data were from the 2005-2006 Arthritis Conditions Health Effects Survey, a cross-sectional random-digit-dialed national telephone survey of noninstitutionalized US adults ages > or = 45 years with self-reported, doctor-diagnosed arthritis. Respondents (n = 1,793; weighted population 37.7 million) were asked if they currently volunteer (work outside the home without pay). Volunteers were asked if arthritis affects their amount or type of volunteering (arthritis-attributable volunteer limitation [AAVL]). Non-volunteers were asked if arthritis is the main reason they do not volunteer (AMBV). Univariable and multivariable-adjusted logistic regression analyses were performed to estimate associations between potential correlates and each outcome. RESULTS: One-third of the respondents reported volunteering. Among volunteers, 41% (4.9 million) reported AAVL. Among non-volunteers, 27% (6.8 million) reported AMBV. Fair/poor self-rated health was significantly associated with less volunteering (multivariable-adjusted odds ratio [OR] 0.5, 95% confidence interval [95% CI] 0.4-0.8) and greater AAVL (multivariable-adjusted OR 2.1, 95% CI 1.1-4.0) and AMBV (multivariable-adjusted OR 1.8, 95% CI 1.2-2.7). Poor physical function was the most strongly associated correlate of both AAVL and AMBV (multivariable-adjusted ORs 8.0 and 4.3, respectively). CONCLUSION: Volunteering is an important role with individual and societal benefits, but almost 12 million adults with arthritis are limited or do not participate in volunteering due to arthritis. Individuals with restrictions in volunteering reported a substantial burden of poor physical function and may benefit from effective, underused interventions designed to improve physical function, delay disability, and enhance arthritis self-management. |
Mycoplasma hominis infection of Trichomonas vaginalis is not associated with metronidazole-resistant trichomoniasis in clinical isolates from the United States
Butler SE , Augostini P , Secor WE . Parasitol Res 2010 107 (4) 1023-7 Trichomonas vaginalis is a protozoan parasite that is the cause of the most common non-viral sexually transmitted disease, trichomoniasis. Metronidazole and tinidazole are the only drugs approved for treatment of T. vaginalis infections in the USA. However, drug resistance exists and some patients are allergic to these medications. Furthermore, the exact mechanism of metronidazole resistance remains undefined and current testing methods require several weeks before results are available. Identification of the mechanism of drug resistance may lead to the development of molecular tools to detect drug resistance, and quicker results for clinical treatment. In a recent study, Chinese T. vaginalis isolates that were polymerase chain reaction (PCR) positive for Mycoplasma hominis DNA demonstrated greater in vitro resistance to metronidazole than isolates with no evidence of M. hominis infection. To evaluate this finding in isolates from a distinct epidemiologic setting, we tested 55 T. vaginalis isolates collected from patients in the USA through the Centers for Disease Control and Prevention metronidazole susceptibility testing service. One half of the isolates demonstrated resistance to metronidazole by an in vitro sensitivity assay. Of the metronidazole-resistant T. vaginalis isolates, 18% were PCR positive for M. hominis, as were 22% of the metronidazole-susceptible T. vaginalis isolates (p = 0.746). We also observed no change in metronidazole sensitivity of two infected T. vaginalis isolates after they were cleared of their M. hominis infection by culturing the isolates in antibiotics. Thus, M. hominis infection of USA T. vaginalis isolates did not correlate with in vitro resistance to metronidazole. |
Nevirapine-associated hepatotoxicity was not predicted by CD4 count ≥250 cells/muL among women in Zambia, Thailand and Kenya
Peters P , Stringer J , McConnell MS , Kiarie J , Ratanasuwan W , Intalapaporn P , Potter D , Mutsotso W , Zulu I , Borkowf CB , Bolu O , Brooks JT , Weidle PJ . HIV Med 2010 11 (10) 650-60 OBJECTIVE: The aim of the study was to determine risk factors for developing severe hepatotoxicity (grade 3 or 4 hepatotoxicity) and rash-associated hepatotoxicity (rash with ≥grade 2 hepatotoxicity) among women initiating nevirapine-based antiretroviral therapy (ART). METHODS: The Non-Nucleoside Reverse Transcriptase Inhibitor Response Study was a prospective cohort study carried out in Zambia, Thailand and Kenya. Between May 2005 and January 2007, we enrolled antiretroviral-naive HIV-infected women initiating nevirapine-based ART. At enrolment and at weeks 2, 4, 8, 16 and 24, participants had serum alanine transferase (ALT) and aspartate transaminase (AST) measured and were evaluated clinically for hepatitis and rash. RESULTS: Nevirapine-based ART was initiated in 820 women and baseline ALT or AST results were abnormal (≥grade 1) in 113 (14%) women. After initiating nevirapine-based ART, severe hepatotoxicity occurred in 41 (5%) women and rash-associated hepatotoxicity occurred in 27 (3%) women. In a multivariate logistic regression model, severe hepatotoxicity and rash-associated hepatotoxicity were both associated with baseline abnormal (≥grade 1) ALT or AST results, but not with a baseline CD4 cell count ≥250 cells/muL. Three participants (0.4%) died with symptoms suggestive of fatal hepatotoxicity; all three women had baseline CD4 count <100 cells/muL and were receiving anti-tuberculosis therapy. CONCLUSION: Among women taking nevirapine-based ART, severe hepatotoxicity and rash-associated hepatotoxicity were predicted by abnormal baseline ALT or AST results, but not by a CD4 count ≥250 cells/muL. In resource-limited settings where transaminase testing is available, testing should focus on early time-points and on women with abnormal baseline ALT or AST results. |
Preventing influenza coinfection among HIV-infected persons: a complex picture coming into focus
Reyes-Teran G , Butera ST . AIDS 2010 24 (14) 2283-5 The impact of seasonal influenza in patients with HIV infection has been debated in the medical literature and systematic clinical guidance on treatment and benefits of vaccination has yet to clearly emerge, in part owing to limited data. A significant excess mortality due to pneumonia or influenza has been found in this population [1], but a typical clinical presentation and a rate of secondary complications similar to those of non-HIV infected individuals have also been reported [2]. Without question, HAART has improved the clinical course of HIV-infected individuals and significantly decreased mortality [3], and hospitalization rates owing to cardiopulmonary disease [4]. Similar therapeutic benefit may be deduced from initial reports focused on HIV-infected persons with the pandemic influenza virus A (H1N1) during 2009. One such study involved 20 HIV patients on HAART (median CD4 cell count of 494 cells/μl; viral load of <400 copies/ml), the clinical presentation of influenza disease was not distinctive from that reported in HIV-negative individuals, and a favorable outcome was observed in the majority of individuals [5]. Another study included 56 individuals with controlled HIV infection (median CD4 cell count of 583 cells/μl; 95% had <50 copies/ml); HIV infection did not make influenza A (H1N1) more clinically severe and influenza A (H1N1) did not have a major effect on clinical measures of HIV infection [6]. In contrast, among patients with advanced HIV disease, H1N1 infection appeared more severe with clinical and radiographic symptoms masked by active opportunistic infections, thus delaying H1N1 antiviral treatment [7]. These initial studies clearly suggest that stage of HIV disease and accessibility of HAART must be considered when estimating the impact of influenza. |
High rate of pneumococcal bacteremia in a prospective cohort of older children and adults in an area of high HIV prevalence in rural western Kenya
Feikin DR , Jagero G , Aura B , Bigogo GM , Oundo J , Beall BW , Karani A , Morpeth S , Njenga MK , Breiman RF . BMC Infect Dis 2010 10 186 BACKGROUND: Although causing substantial morbidity, the burden of pneumococcal disease among older children and adults in Africa, particularly in rural settings, is not well-characterized. We evaluated pneumococcal bacteremia among 21,000 persons > or =5 years old in a prospective cohort as part of population-based infectious disease surveillance in rural western Kenya from October 2006-September 2008. METHODS: Blood cultures were done on patients meeting pre-defined criteria--severe acute respiratory illness (SARI), fever, and admission for any reason at a referral health facility within 5 kilometers of all 33 villages where surveillance took place. Serotyping of Streptococcus pneumoniae was done by latex agglutination and quellung reaction and antibiotic susceptibility testing was done using broth microdilution. We extrapolated incidence rates based on persons with compatible illnesses in the surveillance population who were not cultured. We estimated rates among HIV-infected persons based on community HIV prevalence. We projected the national burden of pneumococcal bacteremia cases based on these rates. RESULTS: Among 1,301 blood cultures among persons > or =5 years, 52 (4%) yielded pneumococcus, which was the most common bacteria isolated. The yield was higher among those > or =18 years than 5-17 years (6.9% versus 1.6%, p < 0.001). The highest yield was for inpatients with SARI (10%), compared with SARI outpatients (3%) and acute febrile outpatients (1%). Serotype 1 pneumococcus was most common (42% isolates) and 71% were serotypes included in the 10-valent pneumococcal conjugate vaccine (PCV10). Non-susceptibility to beta-lactam antibiotics was low (<5%), but to trimethoprim-sulfamethoxazole was high (>95%). The crude rate of pneumococcal bacteremia was 129/100,000 person-years, and the adjusted rate was 419/100,000 person-years. Nineteen (61%) of 31 patients with HIV results were HIV-positive. The adjusted rate among HIV-infected persons was 2,399/100,000 person-years (Rate ratio versus HIV-negative adults, 19.7, 95% CI 12.4-31.1). We project 58,483 cases of pneumococcal bacteremia will occur in Kenyan adults in 2010. CONCLUSIONS: Pneumococcal bacteremia rates were high among persons > or =5 years old, particularly among HIV-infected persons. Ongoing surveillance will document if expanded use of highly-active antiretroviral treatment for HIV and introduction of PCV10 for Kenyan children (anticipated in late 2010) result in substantial secondary benefits by reducing pneumococcal disease in adults. |
Increasing public health partner services for human immunodeficiency virus: results of a second national survey
Katz DA , Hogben M , Dooley Jr SW , Golden MR . Sex Transm Dis 2010 37 (8) 469-75 BACKGROUND: Recent US national efforts taken to prevent human immunodeficiency virus (HIV) infection have emphasized HIV case-finding, including partner services (PS). METHODS: We collected data on HIV PS procedures and outcomes in 2006 from health departments in US metropolitan areas with the highest number of cases of acquired immunodeficiency syndrome, gonorrhea, chlamydial infection, and primary and secondary syphilis, and compared our results with the data collected through a similar study carried out in 2001. RESULTS: Of the 71 eligible jurisdictions, 51 (72%) participated in this study. In 2006, health departments interviewed 11,270 (43%) of the 26,185 persons with newly reported HIV, which was an increase from the 32% reported in 2001 (P < 0.01). Among 10,498 potentially exposed partners, 2228 (21%) had been previously diagnosed with HIV, 803 (8%) were newly HIV-diagnosed, 3337 (32%) tested HIV-negative, and 4130 (39%) were not successfully notified, were notified but refused HIV testing and denied previous diagnosis, or did not have an outcome recorded. Combining data from all jurisdictions, public health staff needed to interview 13.6 persons with HIV to identify one new case of infection; this number was unchanged from 2001 (13.8; P = 0.75). CONCLUSION: In the United States, the proportion of persons diagnosed with HIV receiving PS has increased since 2001, whereas HIV case-finding yields have remained stable. Despite this, most people newly diagnosed with HIV still do not receive PS. |
Coverage of nevirapine-based services to prevent mother-to-child HIV transmission in 4 African countries
Stringer EM , Ekouevi DK , Coetzee D , Tih PM , Creek TL , Stinson K , Giganti MJ , Welty TK , Chintu N , Chi BH , Wilfert CM , Shaffer N , Dabis F , Stringer JS . JAMA 2010 304 (3) 293-302 CONTEXT: Few studies have objectively evaluated the coverage of services to prevent transmission of human immunodeficiency virus (HIV) from mother to child. OBJECTIVE: To measure the coverage of services to prevent mother-to-child HIV transmission in 4 African countries. DESIGN, SETTING, AND PATIENTS: Cross-sectional surveillance study of mother-infant pairs using umbilical cord blood samples collected between June 10, 2007, and October 30, 2008, from 43 randomly selected facilities (grouped as 25 service clusters) providing delivery services in Cameroon, Cote d'Ivoire, South Africa, and Zambia. All sites used at least single-dose nevirapine to prevent mother-to-child HIV transmission and some sites used additional prophylaxis drugs. MAIN OUTCOME MEASURE: Population nevirapine coverage, defined as the proportion of HIV-exposed infants in the sample with both maternal nevirapine ingestion (confirmed by cord blood chromatography) and infant nevirapine ingestion (confirmed by direct observation). RESULTS: A total of 27,893 cord blood specimens were tested, of which 3324 were HIV seropositive (12%). Complete data for cord blood nevirapine results were available on 3196 HIV-seropositive mother-infant pairs. Nevirapine coverage varied significantly by site (range: 0%-82%). Adjusted for country, the overall coverage estimate was 51% (95% confidence interval [CI], 49%-53%). In multivariable analysis, failed coverage of nevirapine-based services was significantly associated with maternal age younger than 20 years (adjusted odds ratio [AOR], 1.44; 95% CI, 1.18-1.76) and maternal age between 20 and 25 years (AOR, 1.28; 95% CI, 1.07-1.54) vs maternal age of older than 30 years; 1 or fewer antenatal care visits (AOR, 2.91; 95% CI, 2.40-3.54), 2 or 3 antenatal care visits (AOR, 1.93; 95% CI, 1.60-2.33), and 4 or 5 antenatal care visits (AOR, 1.56; 95% CI, 1.34-1.80) vs 6 or more antenatal care visits; vaginal delivery (AOR, 1.22; 95% CI, 1.03-1.44) vs cesarean delivery; and infant birth weight of less than 2500 g (AOR, 1.34; 95% CI, 1.11-1.62) vs birth weight of 3500 g or greater. CONCLUSION: In this random sampling of sites with services to prevent mother-to-child HIV transmission, only 51% of HIV-exposed infants received the minimal regimen of single-dose nevirapine. |
Safety of contraceptive use among women with peripartum cardiomyopathy: a systematic review
Tepper NK , Paulen ME , Marchbanks PA , Curtis KM . Contraception 2010 82 (1) 95-101 STUDY DESIGN: Women with peripartum cardiomyopathy (PPCM) have significant health risks during subsequent pregnancies and therefore have a critical need for safe and effective contraception. This systematic review examines evidence regarding the safety of contraceptive use among women with PPCM. METHODS: We searched the PubMed database for all primary research articles published through February 2009 that addressed the safety of any contraceptive method among women with PPCM or other cardiomyopathy of any type. RESULTS: Of 110 articles that addressed contraceptive safety among women with cardiac disease, three met our inclusion criteria. In these three studies, which included a total of five women with cardiomyopathy, though not specifically PPCM, cases of hypertension, transient ischemic attack (TIA), thromboembolism or heart failure were found among women with cardiac disease who used hormonal methods of contraception including combined oral contraceptives, progestin-only pills and depot medroxyprogesterone acetate. None of the studies reported any cases of cardiovascular complications or infective endocarditis among women with cardiac disease who used intrauterine devices (IUDs). CONCLUSIONS: We found no data concerning the safety of contraceptive use among women with PPCM, though we did find limited evidence of hypertension, TIA, thromboembolism and heart failure among women with cardiac disease who used hormonal methods of contraception. None of the studies reported any cases of cardiovascular complications or infective endocarditis among women with cardiac disease who used IUDs. Published by Elsevier Inc. |
Contraceptive use among women with inflammatory bowel disease: A systematic review
Zapata LB , Paulen ME , Cansino C , Marchbanks PA , Curtis KM . Contraception 2010 82 (1) 72-85 BACKGROUND: There are theoretical concerns that use of hormonal contraceptives by women with inflammatory bowel disease (IBD) might increase disease relapse and risk of other adverse health outcomes, including thrombosis. In addition, there are concerns that IBD-related malabsorption might decrease the effectiveness of orally ingested contraceptives. The objective of this systematic review was to evaluate the evidence on the safety and effectiveness of contraceptive use among women with IBD. STUDY DESIGN: We searched the PubMed database for peer-reviewed articles relevant to contraceptive use and IBD that were published in any language from inception of the database through February 2009. We used standard abstract forms and grading systems to summarize and assess the quality of the evidence. RESULTS: From 207 articles, we identified 10 studies that met our inclusion criteria. Evidence from five cohort studies (Level II-2, fair to good) suggests no increased risk of IBD relapse with use of oral contraceptives. Evidence from two pharmacokinetic studies (not graded) suggests that women with mild ulcerative colitis and those with an ileostomy following a proctocolectomy with small deal resections have plasma concentrations of steroid hormones after oral ingestion of higher doses of combined oral contraceptives that are similar to the plasma concentrations among healthy volunteers. No studies were found that examined the risk of thrombosis among women with IBD who used hormonal contraceptives. CONCLUSIONS: Limited evidence suggests there is no increased risk of disease relapse among women with IBD who use oral contraceptives, and there seem to be no differences in the absorption of higher-dose combined oral contraceptives between women with mild ulcerative colitis and small Heal resections and healthy women. Published by Elsevier Inc. |
Detection of Dirofilaria immitis (Nematoda: Filarioidea) by polymerase chain reaction in Aedes albopictus, Anopheles punctipennis, and Anopheles crucians (Diptera: Culicidae) from Georgia, USA
Licitra B , Chambers EW , Kelly R , Burkot TR . J Med Entomol 2010 47 (4) 634-638 Potential mosquito vectors of Dirofilaria immitis (Leidy) (Nematoda: Filarioidea), the causative agent of dog heartworm in the southeastern region of the United States, were collected with CDC light traps and gravid traps in seven counties in the state of Georgia, USA. The presence of D. immitis in these mosquitoes was detected by polymerase chain reaction using species-specific primers for the D. immitis surface or cuticular antigen. Overall, 1,574 mosquitoes of 13 species in seven genera were collected; 92% of the specimens were Aedes albopictus (Skuse), Aedes vexans (Meigen), or Anopheles punctipennis (Say). Ae. albopictus, An. punctipennis, and Anopheles crucians Wiedemann were positive for D. immitis DNA. Ae. albopictus had the highest maximum likelihood rate of infection (2.30%; 95% confidence interval [CI] = 1.15-4.00%) followed by An. crucians (1.38%: 95% CI = 0.04-6.93%), and An. punctipennis (0.85%; 95% CI 0.03-4.29%). The detection of D. immitis DNA in the heads and thoraxes of Ae. albopictus (0.40%; 95% CI = 0.12-2.02%) indicates that these mosquitoes can support the development of D. immitis to the infective stage 3 larvae. |
The elderly as a sensitive population in environmental exposures: making the case
Risher JF , Todd GD , Meyer D , Zunker CL . Rev Environ Contam Toxicol 2010 207 95-157 The population of the United States is aging. A demographic shift of the average age in the United States is occurring rapidly and unavoidably. According to estimates, 20% of all Americans will be 65 or older by the year 2030 (CDC 2004), which is a serious concern for physicians and medical science (Geokas et al. 1990). Further, the average 75-year-old has three chronic medical conditions and uses five prescription drugs (CDC 2004; Qato et al. 2008). It is now recognized that infants and small children are not just miniature adults. Children have many unique anatomic, developmental, physiologic, immunologic, and psychological considerations (Milla 2002; WHO 2005; Williams et al. 2006). They have special nutritional and medical needs because of the immature state of their physiological and anatomical development. Similarly, the elderly are not just older adults with the same needs as healthy young adults. The US Centers for Disease Control and Prevention (CDC) recognizes this difference and states that older adults have unique challenges and different medical needs than younger adults (CDC 2004). |
Seroprevalence of antibody to mumps virus in the US population, 1999-2004
Kutty PK , Kruszon-Moran DM , Dayan GH , Alexander JP , Williams NJ , Garcia PE , Hickman CJ , McQuillan GM , Bellini WJ . J Infect Dis 2010 202 (5) 667-74 BACKGROUND: In 2006, the largest mumps outbreak in the United States in 20 years occurred. To understand prior mumps seroprevalence and factors associated with the presence of antibody to mumps virus, data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES) were analyzed. METHODS: A mumps virus-specific enzyme immunoassay was used to measure the seroprevalence of serum immunoglobulin G (IgG) antibody among NHANES participants aged 6-49 years. Participants were grouped on the basis of 10-year birth cohorts, 95% confidence intervals (CIs) were calculated using SUDAAN software, and logistic regression was used to identify independent predictors. RESULTS: The overall age-adjusted seroprevalence of IgG antibody to mumps virus during 1999-2004 was 90.0% (95% CI, 88.8%-91.1%). Seroprevalence was higher among US-born non-Hispanic blacks (96.4% [95% CI, 95.5%-97.2%]) and non-US-born Mexican Americans (93.7% [95% CI, 92.0%-95.2%]). Seroprevalence was significantly lower in the 1967-1976 birth cohort (85.7% [95% CI, 83.5%-87.8%]). The variables sex, education, and race/ethnicity/birthplace were independent predictors in at least 1 of the birth cohorts. CONCLUSIONS: The overall estimate of 90.0% is at the lower end of the estimated population immunity (90%-92%) needed to achieve herd immunity. Lower seroprevalence among groups suggest that they represent populations at an increased risk. For mumps control, high vaccine coverage and high population immunity must be achieved and maintained. |
Should people who have joint symptoms, but no diagnosis of arthritis from a doctor, be included in surveillance efforts?
Bolen J , Helmick CG , Sacks JJ , Gizlice Z , Potter C . Arthritis Care Res (Hoboken) 2010 63 (1) 150-4 OBJECTIVE: In 2005, 27% of adults reported doctor-diagnosed arthritis (DrDx), and 14% reported chronic joint symptoms but no DrDx (i.e., possible arthritis [PA]). We evaluate the value of including persons classified as PA in surveillance of arthritis. METHODS: In 2005, Kansas, Oklahoma, North Carolina, and Utah added extra questions to their Behavioral Risk Factor Surveillance System (BRFSS) telephone survey targeted to a subsample of those classified as PA. RESULTS: Persons classified as PA (n = 2,884) were younger, more often male, and had less activity limitation than persons with DrDx. Of those classified as PA, half had seen a doctor for their symptoms, 12.5% reported arthritis; 61.9% gave other causes. Of the half who had not seen a doctor, most reported mild symptoms (64.8%). CONCLUSION: Only 6.3% of those classified as PA had what we considered arthritis. Most who did not see a doctor reported mild symptoms and, thus, would be unlikely to be amenable to medical and public health interventions for arthritis. Although including PA would slightly improve the sensitivity of detecting arthritis in the population, it would increase false positives that would interfere with targeting state intervention efforts and burden estimates. The ability to add back questions in BRFSS allows reintroduction of PA should national surveillance suggest it is warranted or studies document an increased rate at which PA turns into arthritis. Currently PA does not need to be included in state arthritis surveillance efforts, and limited question space on surveys is better spent on other arthritis issues. |
Progressive multifocal leukoencephalopathy deaths in the USA, 1979-2005
Yorita Christensen KL , Holman RC , Hammett TA , Belay ED , Schonberger LB . Neuroepidemiology 2010 35 (3) 178-184 BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a neurological disease most often seen among immunosuppressed patients. The incidence of PML increased with an increasing incidence of HIV/AIDS. We describe recent trends and the epidemiology of PML-associated death in the era of highly active antiretroviral therapy (HAART). METHODS: National multiple-cause-of-death data for the USA were used to identify records with PML listed as a cause of death during 1979-2005. Age-adjusted PML-associated death rates were calculated overall and by sex, race, region and HIV status. RESULTS: The PML-associated death rates peaked in the mid-1990s and decreased from 2.76 deaths per 1 million persons in 1992-1995 to 0.66 in 2002-2005. This decrease was mainly due to a decreasing death rate among PML decedents with HIV diagnosis, males and those aged 20-49 years at death. A decline in death rate was also seen among PML decedents without HIV diagnosis, although this trend was not significant. Decedents in the latter time period were more often female, and older. The proportion of HIV-associated deaths from PML decreased between 1992-1995 (1.4%) and 2002-2005 (1.0%). CONCLUSION: PML mortality has decreased significantly since 1996 when HAART became the standard of care in the USA. This decline likely reflects increased survival among HIV-positive persons who receive HAART. |
Epidemic history and evolutionary dynamics of hepatitis B virus infection in two remote communities in rural Nigeria
Forbi JC , Vaughan G , Purdy MA , Campo DS , Xia GL , Ganova-Raeva LM , Ramachandran S , Thai H , Khudyakov YE . PLoS One 2010 5 (7) e11615 BACKGROUND: In Nigeria, hepatitis B virus (HBV) infection has reached hyperendemic levels and its nature and origin have been described as a puzzle. In this study, we investigated the molecular epidemiology and epidemic history of HBV infection in two semi-isolated rural communities in North/Central Nigeria. It was expected that only a few, if any, HBV strains could have been introduced and effectively transmitted among these residents, reflecting limited contacts of these communities with the general population in the country. METHODS AND FINDINGS: Despite remoteness and isolation, approximately 11% of the entire population in these communities was HBV-DNA seropositive. Analyses of the S-gene sequences obtained from 55 HBV-seropositive individuals showed the circulation of 37 distinct HBV variants. These HBV isolates belong predominantly to genotype E (HBV/E) (n=53, 96.4%), with only 2 classified as sub-genotype A3 (HBV/A3). Phylogenetic analysis showed extensive intermixing between HBV/E variants identified in these communities and different countries in Africa. Quasispecies analysis of 22 HBV/E strains using end-point limiting-dilution real-time PCR, sequencing and median joining networks showed extensive intra-host heterogeneity and inter-host variant sharing. To investigate events that resulted in such remarkable HBV/E diversity, HBV full-size genome sequences were obtained from 47 HBV/E infected persons and P gene was subjected to Bayesian coalescent analysis. The time to the most recent common ancestor (tMRCA) for these HBV/E variants was estimated to be year 1952 (95% highest posterior density (95% HPD): 1927-1970). Using additional HBV/E sequences from other African countries, the tMRCA was estimated to be year 1948 (95% HPD: 1924-1966), indicating that HBV/E in these remote communities has a similar time of origin with multiple HBV/E variants broadly circulating in West/Central Africa. Phylogenetic analysis and statistical neutrality tests suggested rapid HBV/E population expansion. Additionally, skyline plot analysis showed an increase in the size of the HBV/E-infected population over the last approximately 30-40 years. CONCLUSIONS: Our data suggest a massive introduction and relatively recent HBV/E expansion in the human population in Africa. Collectively, these data show a significant shift in the HBV/E epidemic dynamics in Africa over the last century. |
How valid are the rates of Down syndrome internationally? Findings from the International Clearinghouse for Birth Defects Surveillance and Research
Leoncini E , Botto LD , Cocchi G , Anneren G , Bower C , Halliday J , Amar E , Bakker MK , Bianca S , Canessa Tapia MA , Castilla EE , Csaky-Szunyogh M , Dastgiri S , Feldkamp ML , Gatt M , Hirahara F , Landau D , Lowry RB , Marengo L , McDonnell R , Mathew TM , Morgan M , Mutchinick OM , Pierini A , Poetzsch S , Ritvanen A , Scarano G , Siffel C , Sipek A , Szabova E , Tagliabue G , Vollset SE , Wertelecki W , Zhuchenko L , Mastroiacovo P . Am J Med Genet A 2010 152A (7) 1670-80 Rates of Down syndrome (DS) show considerable international variation, but a systematic assessment of this variation is lacking. The goal of this study was to develop and test a method to assess the validity of DS rates in surveillance programs, as an indicator of quality of ascertainment. The proposed method compares the observed number of cases with DS (livebirths plus elective pregnancy terminations, adjusted for spontaneous fetal losses that would have occurred if the pregnancy had been allowed to continue) in each single year of maternal age, with the expected number of cases based on the best-published data on rates by year of maternal age. To test this method we used data from birth years 2000 to 2005 from 32 surveillance programs of the International Clearinghouse for Birth Defects Surveillance and Research. We computed the adjusted observed versus expected ratio (aOE) of DS birth prevalence among women 25-44 years old. The aOE ratio was close to unity in 13 programs (the 95% confidence interval included 1), above 1 in 2 programs and below 1 in 18 programs (P < 0.05). These findings suggest that DS rates internationally can be evaluated simply and systematically, and underscores how adjusting for spontaneous fetal loss is crucial and feasible. The aOE ratio can help better interpret and compare the reported rates, measure the degree of under- or over-registration, and promote quality improvement in surveillance programs that will ultimately provide better data for research, service planning, and public health programs. |
Contraception matters: two approaches to analyzing evidence of the abortion decline in Georgia
Serbanescu F , Stupp P , Westoff C . Int Perspect Sex Reprod Health 2010 36 (2) 99-110 CONTEXT: The abortion rate in the republic of Georgia is the highest documented in the world. Analyses using reliable data are needed to inform programs for preventing unintended pregnancy and abortion. METHODS: Data from two large national household surveys conducted in 1999 and 2005 were used to assess the relationship between contraceptive use and abortion. Two analytic approaches were used. First, abortion rates were estimated for three subgroups: users of modern contraceptives, users of traditional contraceptives and nonusers of contraceptives. A decomposition method was then used to estimate the proportions of change in abortion rates that were due to changes in contraceptive use and to changes in use- and nonuse-specific abortion rates. Second, a methodology developed by Westoff was used to examine abortion rates among contraceptive users and among nonusers with differing risks of unintended pregnancy. RESULTS: According to data from the 60 months before each survey, contraceptive prevalence among married women increased by 23% (from 39% to 48%) and the marital abortion rate declined by 15% (from 203 to 172 abortions per 1,000 woman-years) between 1999 and 2005. Both approaches showed that nonuse of any method was the principal determinant of the high unintended pregnancy rate and that the increase in use of modern contraceptives was a significant contributor to the recent drop in abortion (explaining 54% of the decline, according to the decomposition analysis). CONCLUSIONS: Efforts to increase availability and use of modern family planning methods in Georgia should lead to a direct and measurable decline in the abortion rate. |
Coverage bias in variances, associations, and total error from exclusion of the cell phone-only population in the United States
Peytchev A , Carley-Baxter LR , Black MC . Soc Sci Comput Rev 2010 28 (3) 287-302 Although landline telephone household surveys often draw inference about the general population, a proportion with only cell phones is excluded. In the United States, like in much of the world, this proportion is substantial and increasing, providing potential for coverage bias. Studies have looked at bias in means, but undercoverage can affect other essential statistics. The precision of point estimates can be biased, leading to erroneous conclusions. Research examining multivariate relationships will be further affected by bias in associations. A national landline telephone survey was conducted, followed by a survey of adults with only cell phones. In addition to estimates of means and proportions, differences were found for variances and associations. Bias in some point estimates was reduced through poststratification but became larger and in opposite direction for others. Different uses of survey data can be affected by omitting the cell-only population, and reliance on postsurvey adjustments can be misleading. |
Diagnostic X-ray examinations and increased chromosome translocations: evidence from three studies
Bhatti P , Yong LC , Doody MM , Preston DL , Kampa DM , Ramsey MJ , Ward EM , Edwards AA , Ron E , Tucker JD , Sigurdson AJ . Radiat Environ Biophys 2010 49 (4) 685-92 Controversy regarding potential health risks from increased use of medical diagnostic radiologic examinations has come to public attention. We evaluated whether chromosome damage, specifically translocations, which are a potentially intermediate biomarker for cancer risk, was increased after exposure to diagnostic X-rays, with particular interest in the ionizing radiation dose-response below the level of approximately 50 mGy. Chromosome translocation frequency data from three separately conducted occupational studies of ionizing radiation were pooled together. Studies 1 and 2 included 79 and 150 medical radiologic technologists, respectively, and study 3 included 83 airline pilots and 50 university faculty members (total = 155 women and 207 men; mean age = 62 years, range 34-90). Information on personal history of radiographic examinations was collected from a detailed questionnaire. We computed a cumulative red bone marrow (RBM) dose score based on the numbers and types of X-ray examinations reported with 1 unit approximating 1 mGy. Poisson regression analyses were adjusted for age and laboratory method. Mean RBM dose scores were 49, 42, and 11 for Studies 1-3, respectively (overall mean = 33.5, range 0-303). Translocation frequencies significantly increased with increasing dose score (P < 0.001). Restricting the analysis to the lowest dose scores of under 50 did not materially change these results. We conclude that chromosome damage is associated with low levels of radiation exposure from diagnostic X-ray examinations, including dose scores of approximately 50 and lower, suggesting the possibility of long-term adverse health effects. |
Genetic factors associated with elevated carbapenem resistance in KPC-producing Klebsiella pneumoniae
Kitchel B , Rasheed JK , Endimiani A , Hujer AM , Anderson KF , Bonomo RA , Patel JB . Antimicrob Agents Chemother 2010 54 (10) 4201-7 In the United States, the most prevalent mechanism of carbapenem resistance among Enterobacteriaceae is the production of a Klebsiella pneumoniae carbapenemase (KPC). KPC-producing isolates often exhibit a range of carbapenem MICs. To better understand the factors that contribute to overall carbapenem resistance, we analyzed 27 KPC-producing K. pneumoniae isolates with different levels of carbapenem resistance: 11 with low-level (i.e., meropenem or impenem MIC ≤ 4 mug/ml), 2 with intermediate-level (i.e., meropenem and imipenem MIC = 8 mug/ml), and 14 with high-level carbapenem resistance (i.e., imipenem or meropenem MIC ≥ 16 mug/ml) that were received from throughout the U.S. Among 14 isolates that exhibited high-level carbapenem resistance, Western blot analysis indicated that 10 produced an elevated amount of KPC. These isolates contained either an increased blaKPC gene copy number (n = 3) or the presence of deletions directly upstream of the blaKPC gene (n = 7). Four additional isolates lacked elevated KPC production but had high-level carbapenem resistance. Porin sequencing analysis identified 22 isolates potentially lacking a functional OmpK35, and three isolates potentially lacking a functional OmpK36. The highest carbapenem MICs were found in two isolates that lacked both functioning porins and contained elevated KPC production. The 11 isolates with low-level carbapenem resistance contained neither an upstream deletion nor increased blaKPC copy number. These results suggest that both blaKPC copy number and deletions in the upstream genetic environment affect the level of KPC production, and may contribute to high-level carbapenem resistance in KPC-producing K. pneumoniae, particularly when coupled with OmpK36 porin-loss. |
The epidemiology of stroke in the Middle East and North Africa
Tran J , Mirzaei M , Anderson L , Leeder SR . J Neurol Sci 2010 295 38-40 Stroke is the second leading cause of death in the world. In the Middle East and North Africa stroke is increasingly becoming a major health problem, with projections that deaths from it will nearly double by 2030. This systematic review aims to bring together age-adjusted epidemiological data of stroke in this region. A literature review of five databases was conducted. Twenty-three papers met the criteria. The incidence of stroke varied extensively among studies. Studies reported rates from 29.8 per 100000 people in Saudi Arabia to 57 per 100000 people in Bahrain. Furthermore, the 28-day case mortality rate also differed among studies, ranging from 10% in Kuwait to 31.5% in Iran. The rates are comparable with those in the Western world; however, the population of the region is younger. The Middle East and North Africa are lacking in data on the epidemiology of stroke. There is an urgent need to develop strategies to prevent and better care for stroke patients in the Middle East and North Africa. |
Prevention and management of obesity in nonpregnant women and adolescents: beliefs and practices of U.S. obstetricians and gynecologists
Cogswell ME , Power ML , Sharma AJ , Schulkin J . J Womens Health (Larchmt) 2010 19 (9) 1625-34 OBJECTIVE: To describe associations between dissemination of educational materials and U.S. obstetrician/gynecologists' prevention and management of obesity in nonpregnant patients. METHODS: Cross-sectional surveys mailed to 806 and 787 members of the American College of Obstetrician and Gynecologists (ACOG) Collaborative Ambulatory Research Network in February-April 2005 and March-May 2007, respectively, before and after dissemination of ACOG Committee Opinions. RESULTS: Compared with participants in 2005 (n = 437), the proportion of participants in 2007 (n = 433) who reported they would screen nonpregnant adult patients using body mass index (BMI), counsel patients most of the time about physical activity, and ever prescribed weight loss medications increased from 84% to 91%, 48% to 55%, and 40% to 48%, respectively (p < 0.05 for all comparisons). In contrast, reported frequencies of counseling or referring nonpregnant patients for weight control were not significantly different (p > 0.05). In 2007, 33% reported counseling most of the time, and 70% reported referral at least sometimes. A lower proportion of 2007 participants indicated it was likely or very likely that patients would follow advice about physical activity or diet or they can help patients lose weight (p < 0.01 for all comparisons). For adolescent patients, 43% and 24% of participants reported counseling most of the time about physical activity and sedentary activity, respectively. Reported frequency of counseling patients about activity, counseling adult patients about weight control, and prescribing medications was higher among obstetrician/gynecologists who reported reading the Committee Opinions. CONCLUSIONS: Despite decreased optimism about the likelihood of patients following advice, modest improvements occurred in some obstetrician/gynecologists' obesity prevention practices between 2005 and 2007. |
Follow-up of an elementary school intervention for asthma management: do gains last into middle school?
Greenberg C , Luna P , Simmons G , Huhman M , Merkle S , Robin L , Keener D . J Asthma 2010 47 (5) 587-93 OBJECTIVE: Albuquerque Public Schools (APS), in collaboration with the Centers for Disease Control and Prevention, conducted an evaluation to examine whether students who were exposed to the APS asthma program in elementary school retained benefits into middle school. METHODS: APS middle school students who participated in the APS asthma program in elementary school, including the Open Airways for Schools (OAS) education curriculum, responded to a follow-up questionnaire (N = 121) and participated in student focus groups (N = 40). Asthma management self-efficacy scores from the follow-up questionnaire were compared to scores obtained before and after the OAS education component. Additional items assessed students' asthma symptoms, management skills, avoidance of asthma triggers, and school impact. RESULTS: Although asthma management self-efficacy scores declined in middle school among students exposed to the asthma program in elementary school, they remained significantly higher than scores obtained during elementary school prior to the OAS intervention. CONCLUSION: The results indicate that although students benefited from the asthma program delivered in elementary school, they need booster sessions and continued school support in middle school. |
Knowledge of malaria and its association with malaria-related behaviors--results from the Malaria Indicator Survey, Ethiopia, 2007
Hwang J , Graves PM , Jima D , Reithinger R , Kachur SP . PLoS One 2010 5 (7) e11692 BACKGROUND: In 2005, the Ministry of Health in Ethiopia launched a major effort to distribute over 20 million long-lasting insecticidal nets, provide universal access to artemisinin-based combination therapy (ACTs), and train 30,000 village-based health extension workers. METHODS AND FINDINGS: A cross-sectional, nationally representative Malaria Indicator Survey was conducted during the malaria transmission season in 2007. Multivariate logistic regression analyses were performed to assess the effect of women's malaria knowledge on household ITN ownership and women's ITN use. In addition, we investigated the effect of mothers' malaria knowledge on their children under 5 years of age's (U5) ITN use and their access to fever treatment on behalf of their child U5. Malaria knowledge was based on a composite index about the causes, symptoms, danger signs and prevention of malaria. Approximately 67% of women (n=5,949) and mothers of children U5 (n=3,447) reported some knowledge of malaria. Women's knowledge of malaria was significantly associated with household ITN ownership (adjusted Odds Ratio [aOR]=2.1; 95% confidence interval [CI] 1.6-2.7) and with increased ITN use for themselves (aOR=1.8; 95% CI 1.3-2.5). Knowledge of malaria amongst mothers of children U5 was associated with ITN use for their children U5 (aOR=1.6; 95% CI 1.1-2.4), but not significantly associated with their children U5 seeking care for a fever. School attendance was a significant factor in women's ITN use (aOR=2.0; 95% CI 1.1-3.9), their children U5's ITN use (aOR=4.4; 95% CI 1.6-12.1), and their children U5 having sought treatment for a fever (aOR=6.5; 95% CI 1.9-22.9). CONCLUSIONS: Along with mass free distribution of ITNs and universal access to ACTs, delivery of targeted malaria educational information to women could improve ITN ownership and use. Efforts to control malaria could be influenced by progress towards broader goals of improving access to education, especially for women. |
Communication as an essential component of environmental health science
Beato RR , Telfer J . J Environ Health 2010 73 (1) 24-25 The science of health communication | is becoming as central to the field of | environmental health as the science of | epidemiology. Within the 21st century, such | events as Hurricane Katrina, H1N1 influenza, | and concerns about chemical exposure in imported drywall have demonstrated the value | of communication as a means of protecting public health. When such events occur, health | professionals must seek disease control interventions but also address audiences’ information needs. Health communication science is | an essential underpinning for such activities. |
Recombinant H1N1 virus-like particle vaccine elicits protective immunity in ferrets against the 2009 pandemic H1N1 influenza virus
Pushko P , Kort T , Nathan M , Pearce MB , Smith G , Tumpey TM . Vaccine 2010 28 (30) 4771-6 The pandemic virus of 2009 (2009 H1N1) continues to cause illness worldwide, especially in younger age groups. The widespread H1N1 virus infection further emphasizes the need for vaccine strategies that are effective against emerging pandemic viruses and are not dependent on the limitations of traditional egg-based technology. This report describes a recombinant influenza virus-like particle (VLP) vaccine consisting of hemagglutinin (HA), neuraminidase (NA), and matrix (M1) proteins of influenza A/California/04/2009 (H1N1) virus. Influenza H1N1 VLPs with a diameter of approximately 120nm were released into the culture medium from Sf9 insect cells infected with recombinant baculovirus coexpressing HA, NA, and M1 proteins. Purified recombinant H1N1 VLPs morphologically resembled influenza virions and exhibited biological characteristics of influenza virus, including HA and NA activities. In the ferret challenge model, 2009 influenza H1N1 VLPs elicited high-titer serum hemagglutination inhibition (HI) antibodies specific for the 2009 H1N1 virus and inhibited replication of the influenza virus in the upper and lower respiratory tract tissues following A/Mexico/4482/09 (H1N1) virus challenge. Moreover, a single 15mug dose of H1N1 VLPs resulted in complete virus clearance in the ferret lung. These results provide support for the use of recombinant influenza VLP vaccine as an effective strategy against pandemic H1N1 virus. |
Supporting new vaccine introduction decisions: Lessons learned from the Hib Initiative experience
Hajjeh RA , Privor-Dumm L , Edmond K , O'Loughlin R , Shetty S , Griffiths UK , Bear AP , Cohen AL , Chandran A , Schuchat A , Mulholland EK , Santosham M . Vaccine 2010 28 (43) 7123-9 The introduction of Haemophilus influenzae type b (Hib) vaccine in developing countries has suffered from a long delay. Between 2005 and 2009, a surge in Hib vaccine adoption took place, particularly among GAVI-eligible countries. Several factors contributed to the increase in Hib vaccine adoption, including support provided by the Hib Initiative, a project funded by the GAVI Alliance in 2005 to accelerate evidence-informed decisions for use of Hib vaccine. This paper reviews the strategy adopted by the Hib Initiative and the lessons learned in the process, which provide a useful model to accelerate uptake of other new vaccines. |
Varicella vaccine safety and immunogenicity in patients with juvenile rheumatic diseases receiving methotrexate and corticosteroids
Frenck Jr RW , Seward JF . Arthritis Care Res (Hoboken) 2010 62 (7) 903-6 Varicella has been a common rite of passage among children and is typically considered to be a mild disease. However, even among healthy individuals, varicella can cause significant morbidity related to secondary bacterial infections of the excoriated lesions, complications of bacterial sepsis, and virally mediated complications, including pneumonia, encephalitis, and hemorrhagic conditions, that may result in death (1, 2). In 1995, this led to the addition of varicella vaccine (Varivax; Merck) into the routine immunization schedule for children in the US (3). Varicella vaccines are now available throughout the world in both single-antigen and combination (measles, mumps, rubella, and varicella [MMRV]) vaccine formulations, and a number of other countries, including Taiwan, Australia, Canada, Germany, and Uruguay, include varicella vaccine in their routine childhood vaccination program. Globally distributed varicella vaccines, all using the Oka vaccine strain, include Varivax, which is the only varicella vaccine licensed in the US, Okavax (Biken; Sanofi Pasteur), and Varilrix (GlaxoSmithKline). | Varicella-zoster virus (VZV) is a highly cell-associated virus. Because of this, cellular immunity is critical for host defense and recovery from wild-type infection and is also likely to be important in the immune response to vaccination. Therefore, people with altered immune systems, particularly conditions affecting lymphocytes, are at increased risk of severe varicella disease. The prototypical group is children with acute lymphocytic leukemia receiving chemotherapeutic agents. The high morbidity and substantial mortality of varicella among immunocompromised children was the impetus to the development of varicella vaccine in Japan in the 1970s (4). Japanese researchers initially demonstrated the safety and efficacy of the live attenuated varicella vaccine in children with underlying diseases, including nephrotic syndrome and asthma, and then extended their studies to children with leukemia (5). In a large multisite study in the US and Canada, varicella vaccine was administered to children with leukemia in remission. Among the children, 511 had maintenance chemotherapy suspended 2 weeks prior to vaccination and 64 children had completed chemotherapy. A concern raised about the study was that nearly 50% of children in the maintenance chemotherapy group developed a rash postvaccination, some severe enough to require intravenous acyclovir. However, the advantages of avoiding severe, and possibly fatal, wild-type disease were thought to be worth the risk (6). Initial experience showed that approximately 15% of the children with leukemia did not develop antibodies (as measured by the fluorescent antibody to membrane antigen [FAMA] test) after a single dose of vaccine. Therefore, subsequent studies administered 2 doses of varicella vaccine with children receiving the second dose 3 months after the first, resulting in 95% developing antibodies after the second dose. These children were followed closely for varicella exposures and varicella disease over the next 10 years. Of the 123 children who reported a household varicella exposure after receiving 2 doses of varicella vaccine, approximately 85% were protected against developing varicella disease. Based on these studies, although varicella vaccine is not licensed in the US for use in children with leukemia, the vaccine was originally available for use in children with acute lymphocytic leukemia under a special protocol. Current recommendations in the US permit the use of live attenuated vaccines, including varicella vaccine (Varivax), in patients with leukemia, lymphoma, or other malignancies whose disease is in remission, providing their chemotherapy has been terminated for at least 3 months (3). Okavax and Varilrix vaccines are both licensed for use in children with acute lymphocytic leukemia, provided that they are in remission and meet other clinical criteria for vaccination. |
Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures
Klein NP , Fireman B , Yih WK , Lewis E , Kulldorff M , Ray P , Baxter R , Hambidge S , Nordin J , Naleway A , Belongia EA , Lieu T , Baggs J , Weintraub E . Pediatrics 2010 126 (1) e1-8 OBJECTIVE: In February 2008, we alerted the Advisory Committee on Immunization Practices to preliminary evidence of a twofold increased risk of febrile seizures after the combination measles-mumps-rubella-varicella (MMRV) vaccine when compared with separate measles-mumps-rubella (MMR) and varicella vaccines. Now with data on twice as many vaccine recipients, our goal was to reexamine seizure risk after MMRV vaccine. METHODS: Using 2000-2008 Vaccine Safety Datalink data, we assessed seizures and fever visits among children aged 12 to 23 months after MMRV and separate MMR + varicella vaccines. We compared seizure risk after MMRV vaccine to that after MMR + varicella vaccines by using Poisson regression as well as with supplementary regressions that incorporated chart-review results and self-controlled analyses. RESULTS: MMRV vaccine recipients (83,107) were compared with recipients of MMR + varicella vaccines (376,354). Seizure and fever significantly clustered 7 to 10 days after vaccination with all measles-containing vaccines but not after varicella vaccination alone. Seizure risk during days 7 to 10 was higher after MMRV than after MMR + varicella vaccination (relative risk: 1.98 [95% confidence interval: 1.43-2.73]). Supplementary analyses yielded similar results. The excess risk for febrile seizures 7 to 10 days after MMRV compared with separate MMR + varicella vaccination was 4.3 per 10,000 doses (95% confidence interval: 2.6-5.6). CONCLUSIONS: Among 12- to 23-month-olds who received their first dose of measles-containing vaccine, fever and seizure were elevated 7 to 10 days after vaccination. Vaccination with MMRV results in 1 additional febrile seizure for every 2300 doses given instead of separate MMR + varicella vaccines. Providers who recommend MMRV should communicate to parents that it increases the risk of fever and seizure over that already associated with measles-containing vaccines. |
Estimating the vaccine-preventable burden of hospitalized pneumonia among young Mozambican children
Roca A , Sigauque B , Quinto L , Morais L , Berenguera A , Corachan M , Ribo JL , Naniche D , Bassat Q , Sacoor Ch , Nhalungo D , Macete E , Schuchat A , Soriano-Gabarro M , Flannery B , Alonso PL . Vaccine 2010 28 (30) 4851-7 Polysaccharide-protein conjugate vaccines against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae have proven efficacy against radiologically confirmed pneumonia. Measurement of pneumonia incidence provides a platform to estimate of the vaccine-preventable burden. Over 24 months, we conducted surveillance for radiologically confirmed severe pneumonia episodes among children <2 years of age admitted to a rural hospital in Manhica, southern Mozambique. Study children were tested for HIV during the second year of surveillance. Severe pneumonia accounted for 15% of 5132 hospital admissions and 32% of in-hospital mortality among children <2 years of age. Also, 43% of chest radiographs were interpreted as radiologically confirmed pneumonia. HIV-infection was associated with 81% of fatal pneumonia episodes among children tested for HIV. The minimum incidence rate of radiologically confirmed pneumonia requiring hospitalization was 19 episodes/1000 child-years. Incidence rates among HIV-infected children were 9.3-19.0-fold higher than HIV-uninfected. Introduction of Hib and pneumococcal conjugate vaccines would have a substantial impact on pneumonia hospitalizations among African children if vaccine effects are similar to those observed in clinical trials. |
A review of unintentional injuries in adolescents
Sleet DA , Ballesteros MF , Borse NN . Annu Rev Public Health 2010 31 195-212 Unintentional injuries are the largest source of premature morbidity and mortality and the leading cause of death among adolescents 10-19 years of age. Fatal injury rates of males are twice those of females, and racial disparities in injury are pronounced. Transportation is the largest source of these injuries, principally as drivers and passengers, but also as cyclists and pedestrians. Other major causes involve drowning, poisonings, fires, sports and recreation, and work-related injuries. Implementing known and effective prevention strategies such as using seat belts and bicycle and motorcycle helmets, installing residential smoke alarms, reducing misuse of alcohol, strengthening graduated driver licensing laws, promoting policy change, using safety equipment in sports and leisure, and protecting adolescents at work will all contribute to reducing injuries. The frequency, severity, potential for death and disability, and costs of these injuries, together with the high success potential of prevention strategies, make injury prevention a key public health goal to improve adolescent health in the future. |
Lost in translation: Translating injury research into effective interventions
Sleet DA , Baldwin G . J Australas Coll Road Saf 2010 21 (2) 9-12 Despite the existence of many effective interventions, more than1.3 million people worldwide die from road traffic injuries. Another 20 to 50 million suffer serious injuries. Many, if not most of these injuries are preventable. While effective interventions exist to prevent many traffic-related injuries, they are often not available or are simply not used to save lives. This is a problem of translation. |
Ecological approaches to the prevention of unintentional injuries
Allegrante JP , Hanson DW , Sleet DA , Marks R . Ital J Public Health 2010 7 (2) 24-31 BACKGROUND: Injury as a cause of significant morbidity and mortality has remained fairly stable in countries with developed economies. Although injury prevention often is conceptualised as a biomedical construct, such a reductionist perspective overlooks the importance of the psychological, environmental, and sociocultural conditions as contributing factors to injury and its consequences. This paper describes the potential of the ecological model for understanding the antecedent causes of unintentional injuries and guiding injury prevention approaches. We review the origins and conceptualise the elements of the ecological model and conclude with some examples of applications of ecological approaches to the prevention of unintentional injury and promotion of community safety. METHODS: A review of the English-language literature on the conceptualization of ecological models in public health and injury prevention, including the application of the ecological model in the prevention of falls and road traffic injuries and in the community safety promotion movement. RESULTS: Three dimensions are important in social-ecological systems that comprise key determinants of injuries: 1) the individual and his or her behaviour, 2) the physical environment, and 3) the social environment. Social and environmental determinants have profound impact on population health and in the causation of injuries. | CONCLUSIONS: Social and environmental determinants of injury should be studied with the same energy, urgency, and intellectual rigor as physical determinants. Application of the ecological model in injury prevention shows the most promise in falls injury prevention, road traffic injury prevention, and community safety promotion. |
Injury prevention and public health
Sleet DA . Ital J Public Health 2010 7 (2) 3-5 Injuries are one of the most under-recognized public health problems facing the world today. With more than 5 million deaths every year, violence and injuries account for 9% of global mortality, as many deaths as from HIV, Malaria and Tuberculosis combined. Eight of the 15 leading causes of death for people ages 15 to 29 years are injury-related: road traffic injuries, suicides, homicides, drowning, burns, war injuries, poisonings and falls. For every death due to war, there are three deaths due to homicide and five deaths due to suicide. However, most violence happens to people behind closed doors and results not in death, but often in years of physical and emotional suffering [1]. Injuries can be classified by intent: unintentional or intentional. Traffic injuries, fire-related injuries, falls, drowning, and poisonings are most often classified as unintentional injuries; injuries due to assault, selfinflicted violence such as suicide, and war are classified as intentional injuries, or violence. Worldwide, governments and public and private partners are increasingly aware of the strains that unintentional injuries and violence place on societies. In response they are strengthening data collection systems, improving services for victims and survivors, and increasing prevention efforts [1]. |
Drowning in Alaska: progress and persistent problems
Strayer HD , Lucas DL , Hull-Jilly DC , Lincoln JM . Int J Circumpolar Health 2010 69 (3) 253-64 OBJECTIVES: The purpose of this study is to evaluate and describe the current problem of drowning in Alaska, measure changes in the rates since earlier studies have been done and compare occupational and non-occupational drowning characteristics. STUDY DESIGN: This is a descriptive observational study, using existing records obtained from several sources to describe and compare drowning victims and event characteristics. METHODS: Drowning fatality data were collected from death certificates, law-enforcement reports and news articles. Descriptive statistics and risk ratios were calculated to compare levels of risk based on incident and victim characteristics. RESULTS: During 2000-2006, 402 unintentional drowning deaths, 108 of them occupational, occurred in Alaska, with an average annual fatality rate of 8.9 deaths per 100,000 Alaskans. The victim population was 86% male and 44% Alaska Native; 40% drowned in the south-west region of Alaska. For non-occupational cases with alcohol use documented, 33% were associated with alcohol consumption, as were 78% of those involved with all-terrain vehicle crashes. Only 17% of non-occupational victims who drowned while boating wore a Personal Flotation Device (PFD). CONCLUSIONS: The drowning rate in Alaska during 2000-2006 was 8.9 drowning deaths per 100,000 population. This shows a decrease from the rate reported in a 1996 study, but several problems persist. Males and Alaska Natives had elevated risks for drowning. A substantial portion of fatalities were associated with alcohol consumption. PFD use remains low, and child drowning rates were unchanged from earlier studies. Increased data on water temperature and immersion time may help demonstrate the benefits of PFD use to those at risk. Social marketing efforts should be adapted for at-risk populations. |
Two new diterpene phenols from Calocedrus decurrans
Veluthoor S , Li SJ , Kelsey RG , Dolan MC , Panella NA , Karchesy J . Nat Prod Commun 2010 5 (4) 519-522 Two new p-cymene based diphenols (1-2) were isolated from the heartwood of Calocedrus decurrans. Structures were elucidated by ID and 2D NMR techniques and HRMS. Libocedroquinone (3) was also isolated as a natural product for the first time. A new system of nomenclature is proposed for description of such oligomeric p-cymene derivatives. |
Use of monoclonal antibodies against Hendra and Nipah viruses in an antigen capture ELISA
Chiang CF , Lo MK , Rota PA , Spiropoulou CF , Rollin PE . Virol J 2010 7 115 BACKGROUND: Outbreaks of Hendra (HeV) and Nipah (NiV) viruses have been reported starting in 1994 and 1998, respectively. Both viruses are capable of causing fatal disease in humans and effecting great economical loss in the livestock industry. RESULTS: Through screening of hybridomas derived from mice immunized with gamma-irradiated Nipah virus, we identified two secreted antibodies; one reactive with the nucleocapsid (N) protein and the other, the phosphoprotein (P) of henipaviruses. Epitope mapping and protein sequence alignments between NiV and HeV suggest the last 14 amino acids of the carboxyl terminus of the N protein is the target of the anti-N antibody. The anti-P antibody recognizes an epitope in the amino-terminal half of P protein. These monoclonal antibodies were used to develop two antigen capture ELISAs, one for virus detection and the other for differentiation between NiV and HeV. The lower limit of detection of the capture assay with both monoclonal antibodies was 400 pfu. The anti-N antibody was used to successfully detect NiV in a lung tissue suspension from an infected pig. CONCLUSION: The antigen capture ELISA developed is potentially affordable tool to provide rapid detection and differentiation between the henipaviruses. |
Validation of the GenoType MTBDRplus assay for detection of MDR-TB in a public health laboratory in Thailand
Anek-Vorapong R , Sinthuwattanawibool C , Podewils LJ , McCarthy K , Ngamlert K , Promsarin B , Varma JK . BMC Infect Dis 2010 10 123 BACKGROUND: Over the past several years, new diagnostic techniques have been developed to allow for the rapid detection of multidrug resistant tuberculosis. The GenoType MTBDRplus test is a deoxyribonucleic acid (DNA) strip assay which uses polymerase chain reaction (PCR) and hybridization to detect genetic mutations in the genes that confer isoniazid (INH) and rifampn (RIF) resistance. This assay has demonstrated good performance and a rapid time to results, making this a promising tool to accelerate MDR-TB diagnosis and improve MDR-TB control. Validation of rapid tests for MDR-TB detection in different settings is needed to ensure acceptable performance, particularly in Asia, which has the largest number of MDR-TB cases in the world but only one previous report, in Vietnam, about the performance of the GenoType MDRplus assay. Thailand is ranked 18th of 22 "high-burden" TB countries in the world, and there is evidence to suggest that rates of MDR-TB are increasing in Thailand. We compared the performance of the GenoType MTBDRplus assay to Mycobacterial Growth Indicator Tube for Antimycobacterial Susceptibility Testing (MGIT AST) for detection INH resistance, RIF resistance, and MDR-TB in stored acid-fast bacilli (AFB)-positive sputum specimens and isolates at a Public TB laboratory in Bangkok, Thailand. METHODS: 50 stored isolates and 164 stored AFB-positive sputum specimens were tested using both the MGIT AST and the GenoType MTBDRplus assay. RESULTS: The GenoType MTBDRplus assay had a sensitivity of 95.3%, 100%, and 94.4% for INH resistance, RIF resistance, and MDR-TB, respectively. The difference in sensitivity between sputum specimens (93%) and isolates (100%) for INH resistance was not statistically significant (p = 0.08). Specificity was 100% for all resistance patterns and for both specimens and isolates. The laboratory processing time was a median of 25 days for MGIT AST and 5 days for the GenoType MTBDRplus (p < 0.01). CONCLUSION: The GenoType MTBDRplus assay has been validated as a rapid and reliable first-line diagnostic test on AFB-positive sputum or MTB isolates for INH resistance, RIF resistance, and MDR-TB in Bangkok, Thailand. Further studies are needed to evaluate its impact on treatment outcome and the feasibility and cost associated with widespread implementation. |
Optimal swab processing recovery method for detection of bioterrorism-related Francisella tularensis by real-time PCR
Walker RE , Petersen JM , Stephens KW , Dauphin LA . J Microbiol Methods 2010 83 (1) 42-7 Francisella tularensis, the etiological agent of tularemia, is regarded as a potential bioterrorism agent. The advent of bioterrorism has heightened awareness of the need for validated methods for processing environmental samples. In this study we determined the optimal method for processing environmental swabs for the recovery and subsequent detection of F. tularensis by the use of real-time PCR assays. Four swab processing recovery methods were compared: heat, sonication, vortexing, and the Swab Extraction Tube System (SETS). These methods were evaluated using cotton, foam, polyester and rayon swabs spiked with six pathogenic strains of F. tularensis. Real-time PCR analysis using a multi-target 5'nuclease assay for F. tularensis showed that the use of the SETS method resulted in the best limit of detection when evaluated using multiple strains of F. tularensis. We demonstrated also that the efficiency of F. tularensis recovery from swab specimens was not equivalent for all swab processing methodologies and, thus, that this variable can affect real-time PCR assay sensitivity. The effectiveness of the SETS method was independent of the automated DNA extraction method and real-time PCR platforms used. In conclusion, diagnostic laboratories can now potentially incorporate the SETS method into specimen processing protocols for the rapid and efficient detection of F. tularensis by real-time PCR during laboratory bioterrorism-related investigations. |
Porous silicon-based optical microsensors for volatile organic analytes: effect of surface chemistry on stability and specificity
Ruminski AM , King BH , Salonen J , Snyder JL , Sailor MJ . Adv Funct Mater 2010 20 (17) 2874-2883 Sensing of the volatile organic compounds (VOCs) isopropyl alcohol (IPA) and heptane in air using sub-millimeter porous silicon-based sensor elements is demonstrated in the concentration range 50-800 ppm. The sensor elements are prepared as one-dimensional photonic crystals (rugate filters) by programmed electrochemical etch of p++ silicon, and analyte sensing is achieved by measurement of the wavelength shift of the photonic resonance. The sensors are studied as a function of surface chemistry: ozone oxidation, thermal oxidation, hydrosilylation (1-dodecene), electrochemical methylation, reaction with dicholorodimethylsilane and thermal carbonization with acetylene. The thermally oxidized and the dichlorodimethylsilane-modified materials show the greatest stability under atmospheric conditions. Optical microsensors are prepared by attachment of the porous Si layer to the distal end of optical fibers. The acetylated porous Si microsensor displays a greater response to heptane than to IPA, whereas the other chemical modifications display a greater response to IPA than to heptane. The thermal oxide sensor displays a strong response to water vapor, while the acetylated material shows a relatively weak response. The results suggest that a combination of optical fiber sensors with different surface chemistries can be used to classify VOC analytes. Application of the miniature sensors to the detection of VOC breakthrough in a full-scale activated carbon respirator cartridge simulator is demonstrated. |
The effects of tuberculosis, race and human gene SLCO1B1 polymorphisms on rifampin concentrations
Weiner M , Peloquin C , Burman W , Luo CC , Engle M , Prihoda TJ , MacKenzie WR , Bliven-Sizemore E , Johnson JL , Vernon A . Antimicrob Agents Chemother 2010 54 (10) 4192-200 BACKGROUND: Rifampin has concentration-dependent activity against Mycobacterium tuberculosis. However marked inter-subject variation of rifampin concentrations occur. In this study, we evaluated rifampin pharmacokinetics in relation to tuberculosis, geographic region, race, and single nucleotide polymorphisms of human transporter genes SLCO1B1, SLCO1B3 and MDR1. MATERIALS & METHODS: Seventy-two adults with pulmonary tuberculosis from Africa, North America and Spain were evaluated during multi-drug intensive-phase therapy, and compared to 16 healthy controls from North America. RESULTS: Rifampin pharmacokinetics values were similar between tuberculosis patients versus controls (geometric mean [GM] area under the concentration-time curve (AUC0-24) 40.2 vs. 40.9 mcg*h/ml, P=.9). However in multivariable analyses, rifampin AUC0-24 was significantly affected by rifampin dosage (mg/kg), polymorphisms in the SLCO1B1 gene, and presence of tuberculosis by geographic region. Adjusted rifampin AUC0-24 was lowest in patients with tuberculosis from Africa compared to non-African patients or control subjects. Adjusted rifampin AUC0-24 was also 36% lower among participants with SLCO1B1 c.463CA versus c.463CC genotype (adjusted GM 29.8 vs. 46.7 mcg*h/ml, P=.001). Polymorphisms in the SLCO1B1 gene associated with lower rifampin exposure were more frequent among subjects of Black race. CONCLUSIONS: Marked inter-subject variation of rifampin AUC0-24 was observed, but means of AUC0-24 did not significantly vary between patients with tuberculosis and healthy controls. Lower rifampin exposure was associated with the polymorphism of the SLCO1B1 c.463C>A gene. When adjusted for patient mg/kg dosage and transporter gene polymorphisms, rifampin exposure was lower in patients with tuberculosis which suggests that additional absorption or metabolic processes affect rifampin exposure with tuberculosis disease. |
Extrapulmonary tissue responses in cynomolgus macaques (Macaca fascicularis) infected with highly pathogenic avian influenza A (H5N1) virus
Tolnay AE , Baskin CR , Tumpey TM , Sabourin PJ , Sabourin CL , Long JP , Pyles JA , Albrecht RA , Garcia-Sastre A , Katze MG , Bielefeldt-Ohmann H . Arch Virol 2010 155 (6) 905-14 The mechanisms responsible for virulence of influenza viruses in humans remain poorly understood. A prevailing hypothesis is that the highly pathogenic virus isolates cause a severe cytokinemia precipitating acute respiratory distress syndrome and multiple organ dysfunction syndrome. Cynomolgus macaques (Macaca fascicularis) infected with a human highly pathogenic avian influenza (HPAI) H5N1 virus isolate (A/Vietnam/1203/2004) or reassortants of human influenza virus A/Texas/36/91 (H1N1) containing genes from the 1918 pandemic influenza A (H1N1) virus developed severe pneumonia within 24 h postinfection. However, virus spread beyond the lungs was only detected in the H5N1 group, and signs of extrapulmonary tissue reactions, including microglia activation and sustained up-regulation of inflammatory markers, most notably hypoxia inducible factor-1alpha (HIF-1alpha), were largely limited to this group. Extrapulmonary pathology may thus contribute to the morbidities induced by H5N1 viruses. |
Flexible label-free quantitative assay for antibodies to influenza virus hemagglutinins
Carney PJ , Lipatov AS , Monto AS , Donis RO , Stevens J . Clin Vaccine Immunol 2010 17 (9) 1407-16 During the initial pandemic influenza H1N1 virus outbreak, assays such as hemagglutination inhibition and microneutralization, provided important information on the relative protection afforded by the population's cross-reactivity from prior infections and immunizations with seasonal vaccines. However, these assays continue to be limited in that they are difficult to automate for high throughput, such as in pandemic situations, as well as to standardize between labs. Thus, new technologies are being sought to improve standardization, reliability and throughput by using chemically defined reagents rather than whole cells and virions. We now report the use of a cell-free and label-free flu antibody biosensor assay (f-AbBA) for influenza research and diagnostics that utilizes recombinant hemagglutinin (HA) in conjunction with label-free biolayer interferometry technology to measure biomolecular interactions between the HA and specific anti-HA antibodies or sialylated ligands. We evaluated f-AbBA to determine anti-HA antibody binding activity in serum or plasma to assess vaccine-induced humoral responses. This assay can reveal the impact of antigenic difference on antibody binding to HA and also measure binding to different subtypes of HA. We also show that the biosensor assay can measure the ability of HA to bind a model sialylated receptor-like ligand. F-AbBA could be used in global surveillance laboratories since preliminary tests on desiccated HA probes showed no loss of activity after >2 months in storage at room temperature indicating that the same reagent lots could be used in different laboratories to minimize inter-laboratory assay fluctuation. Future development of such reagents and similar technologies may offer a robust platform for future influenza surveillance activities. |
An immunofiltration device for the simultaneous detection of non-treponemal and treponemal antibodies in patients with syphilis
Castro AR , Mody HC , Parab SY , Patel MT , Kikkert SE , Park MM , Ballard RC . Sex Transm Infect 2010 86 (7) 532-6 OBJECTIVE: The development of a rapid immunofiltration (flow-through) test for the simultaneous detection of non-treponemal and treponemal antibodies in the serum of patients with syphilis. METHODS: The assay is rapid, inexpensive, and requires limited expertise in interpreting the results. The test is based on the principle of immunofiltration, with two antigens and control material spotted on the membrane of a through-flow device. A positive test is characterised by the appearance of three red/magenta spots within 2-10 min. RESULTS: A total of 376 banked serum samples obtained from the Georgia Public Health Laboratory was examined by the flow-through test, the rapid plasma reagin (RPR) test and the Treponema pallidum passive particle agglutination assay (TPPA). The sensitivity and specificity of the non-treponemal spot were 96.5% and 97.7%, respectively, when compared with the RPR test, and the sensitivity and specificity of the treponemal test spot were 97.3% and 99.1% when compared with the TPPA test. In addition, the test yielded equivalent results to those obtained in comparator tests when 104 sera from cases of syphilis of known stage, 49 sera from diseases other than syphilis and 23 sera known to exhibit biological false-positive reactions were tested in parallel. CONCLUSIONS: These results indicate that the dual treponemal and non-treponemal assay could be used as a screen and confirmatory test for the serological diagnosis of syphilis in remote or resource-poor settings where there is a need to provide counselling and treatment at the initial consultation. |
Analysis of 4-aminobiphenyl hemoglobin adducts in smokers and nonsmokers by pseudo capillary on-column gas chromatography- tandem mass spectrometry
Seyler TH , Reyes LR , Bernert JT . J Anal Toxicol 2010 34 (6) 304-11 We describe here a hemoglobin adduct assay applied to an analysis of samples from smokers and nonsmokers. The assay includes a sensitive method for quantification of orthotoluidine 2-aminonaphthylene, and 3- and 4-aminobiphenyl hemoglobin adducts in human blood using capillary gas chromatography-tandem mass spectrometry. Basic hydrolysis and derivatization with pentafluoropropionic acid anhydride are followed by programmable temperature vaporization and pseudo on-column capillary gas chromatography with positive electron ionization tandem mass spectrometry analysis. Standard deviation of calibration curves (n = 6) shows that the limits of detection for o-toluidine, 2-aminonaphthylene, and 3- and 4-aminobiphenyl were 0.23, 0.39, 0.30, and 0.24 pg total on-column, respectively. The effective working limit of detection is estimated at approximately 5.22 pg/g Hb and 18.73 pg/g Hb for 4-aminobiphenyl and 2-aminonaphthylene, respectively. In a group that was predominately male and African-American, the level of 4-aminobiphenyl Hb adducts was significantly different between smokers and nonsmokers. Among 93 nonsmokers with serum cotinine concentrations less than 10 ng/mL, the geometric mean (95% CI) concentration of 4-aminobiphenyl was 29.9 pg/g hemoglobin (Hb; 29.4 to 30.4). Conversely, in 100 smokers the 4-aminobiphenyl adducts geometric mean concentration was significantly greater at 73.0 pg/g Hb (72.6 to 73.4). 4-Aminobiphenyl hemoglobin adduct and serum cotinine concentrations were correlated (r = 0.496; p < 0.0001; n = 193). In 15% of smokers, 3-aminobiphenyl was detected at low concentration. Adduct levels of 2-aminonaphthylene and ortho-toluidine were not significantly different between the smoker and nonsmoker participants. Our study shows that 4-aminobiphenyl Hb adducts remain the preferred biomarker for identifying people exposed to aromatic amines from tobacco smoke. |
Comparative evaluation of Taqman real-time PCR and semi-nested VP1 PCR for detection of enteroviruses in clinical specimens
Oberste MS , Penaranda S , Rogers SL , Henderson E , Nix WA . J Clin Virol 2010 49 (1) 73-4 BACKGROUND: Molecular diagnostic tests to detect enterovirus in clinical specimens usually target highly conserved sites in the 5'-non-translated region, allowing detection of all members of the genus. The sequences in the 5'-NTR do not correlate with serotype, but PCR and sequencing of the VP1 region can be used for typing; this system has largely replaced traditional antigenic typing. OBJECTIVE: To investigate the relative performance of two common enterovirus assays. STUDY DESIGN: We compared the relative sensitivities of Taqman((R)) real-time RT-PCR (rRT-PCR) and a VP1 semi-nested PCR (RT-snPCR) assay in which sequencing the VP1 amplicon also provides typing information. RESULTS: There was 89% concordance between the two methods among the 371 clinical specimens tested (74 positive in both assays and 257 negative in both assays). Twenty-seven rRT-PCR-negative/VP1-positive specimens were confirmed positive by sequencing; 13 specimens were rRT-PCR-positive/VP1-negative. CONCLUSIONS: The results suggest that either assay can produce satisfactory results, but that using both assays in parallel should provide the highest sensitivity for clinical diagnostic testing. |
Development and application of a broadly-sensitive dried blood spots-based genotyping assay for global surveillance of HIV-1 drug resistance
Yang C , McNulty A , Diallo K , Zhang J , Titanji B , Kassim S , Wadonda-Kabondo N , Aberle-Grasse J , Kibuka T , Ndumbe PM , Vedapuri S , Zhou Z , Chilima B , Nkengasong JN . J Clin Microbiol 2010 48 (9) 3158-64 As antiretroviral therapy (ART) is scale-up in resource-limited countries, surveillance for HIV drug resistance (DR) is vital to ensure sustained effectiveness of first line ARV. We have developed and applied a broadly-sensitive dried blood spot (DBS)-based genotyping assay for surveillance of HIV-1 DR in international settings. In 2005 and 2006, 171 DBS were collected under field conditions from newly diagnosed HIV-1-infected individuals from Malawi (N=58), Tanzania (N=60), and China (53). In addition, 30 DBS and 40 plasma specimens collected from ART-patients in China and Cameroon, respectively, were also tested. Of the 171 DBS analyzed on the protease and RT regions, 149 (87.1%) were genotyped including 49 (81.7%) from Tanzania, 47 (88.7%) from China, and 53 (91.4%) from Malawi. Among the 70 ART-patient samples analyzed, 100% (30/30) Chinese DBS and 90% (36/40) Cameroonian plasma specimens were genotyped, including 8 samples with viral load <400 copies/ml. Phylogenetic analyses indicated that subtype distributions were as follows: C (34%, 73), B (17.2%, 37), CRF01_AE and CRF02_AG (11.2%, 24 each), A1 (10.2%, 22), unclassifiable (UC) (4.2%, 9). The remaining strains were minor strains comprised of CRF07_BC (2.8%, 6), CRF10_CD (2.3%, 5), URF_A1C and CRF08_BC (1.4%, 3 each), G, URF_BC and D/UC (0.9%, 2 each), and F1, F2 and URF_A1D (0.5%, 1 each). Our results indicate that this broadly-sensitive genotyping assay can be used to genotype DBS collected from areas with diverse HIV-1 group M subtypes and CRFs. Thus, the assay is likely to become a useful screening tool in the global resistance surveillance and monitoring of HIV-1 where multiple subtypes and CRFs are found. |
Dissemination of an enterococcus Inc18-like vanA plasmid, associated with vancomycin-resistant Staphylococcus aureus
Zhu W , Murray PR , Huskins WC , Jernigan JA , McDonald LC , Clark NC , Anderson KF , McDougal LK , Hageman JC , Olsen-Rasmussen M , Frace M , Alangaden GJ , Chenoweth C , Zervos MJ , Robinson-Dunn B , Schreckenberger PC , Reller LB , Rudrik JT , Patel JB . Antimicrob Agents Chemother 2010 54 (10) 4314-20 Of the 9 vancomycin-resistant Staphylococcus aureus (VRSA) cases reported to date in the literature, 7 occurred in Michigan (MI). In 5 out of 7 of the Michigan VRSA cases, an Inc18-like vanA plasmid was identified in the VRSA isolate and/or an associated vancomycin-resistant Enterococcus (VRE) isolate from the same patient. This plasmid may play a critical role in the emergence of VRSA and analysis of the geographical distribution of VRE containing this plasmid may explain the observed prevalence of VRSA in MI. A total of 1,641 VRE from three separate collections were tested for the Inc18-like vanA plasmid by PCR for traA, repR, and vanA. All VRE from 2 MI institutions (N= 386), and between 60 to 70 VRE (N=883) from 17 institutions in 13 other states were tested. Fifteen isolates (3.9%) from MI were positive for an Inc18-like vanA plasmid (9 E. faecalis [12.5%], 3 E. faecium [1.0%], 2 E. avium, and 1 E. raffinosus). Six isolates (0.6%) from outside of MI were positive (3 E. faecalis [2.7%] and 3 E. faecium [0.4%]). Fourteen of the 15 plasmid-positive isolates from MI had the same Tn1546 insertion site location as those of the VRSA-associated Inc18 plasmid whereas 5 out of 6 plasmid-positive isolates from outside of MI differed in this characteristic. The one exception was an E. faecium isolate with a pulsed-field gel electrophoresis (PFGE) pattern that was indistinguishable from a plasmid-positive isolate from MI. Most plasmid-positive E. faecalis demonstrated diverse patterns by PFGE, with the exception of three pairs with indistinguishable patterns, suggesting the plasmid is mobile. Although VRE with the VRSA-associated Inc18-like vanA plasmid were more common in MI, they remain rare. Periodic surveillance of VRE for the plasmid may be useful in predicting occurrence of VRSA. |
Progestogen-only contraceptive use among breastfeeding women: a systematic review
Kapp N , Curtis K , Nanda K . Contraception 2010 82 (1) 17-37 BACKGROUND: The use of progestogen-only contraceptives by breastfeeding women raises theoretical concerns regarding possible adverse effects on breastfeeding success, and infant health or growth. This review was conducted to determine from the literature whether use of progestogen-only contraceptives by breastfeeding women leads to adverse effects on lactation, or infant growth or health when compared to nonuse. STUDY DESIGN: We searched the Medline, Popline, Cochrane and LILACS databases for all articles published from database inception through May 2009. Studies were included if they investigated the use of progestogen-only methods in breastfeeding women and reported on clinical outcomes in either women or their infants. Standard data abstraction templates were used to systematically assess and summarize. Summary odds ratios were not calculated, given the heterogeneity of interventions, results and non-quantifiable outcomes reported. RESULTS: We identified 43 articles for this review. Overall, five randomized trials and 38 observational studies demonstrated no adverse effects of various progestogen-only methods of contraception on multiple measures of breastfeeding performance through 12 months in women using these methods in the postpartum period. Many of these studies also demonstrated no adverse effects of progestogen-only methods on infant growth, health or development from 6 months to 6 years of age. Additional studies demonstrated no effects on infant immunoglobulins or sex hormones of exposed male infants. A single study of a desogestrel pill reported two cases of gynecomastia in exposed infants. CONCLUSIONS: Evidence suggests that progestogen-only methods of contraception do not adversely affect breastfeeding performance when used during lactation. Evidence that progestogen-only contraception does not adversely affect infant growth, health, or development when used by breastfeeding women is consistent but methodologically limited. (C) 2010 Elsevier Inc. All rights reserved. |
Combined oral contraceptive use among breastfeeding women: a systematic review
Kapp N , Curtis KM . Contraception 2010 82 (1) 10-16 BACKGROUND: Postpartum women need effective contraception, but using hormonal contraceptives may affect breastfeeding performance and infant health outcomes. STUDY DESIGN: We searched the MEDLINE and Cochrane databases for all articles published through May 2009 for primary research studies that investigated clinical outcomes among breastfeeding women who used hormonal contraception or their infants. RESULTS: Three randomized controlled trials reported decreased mean duration of breastfeeding and higher rates of supplemental feeding among combined oral contraceptive (COC) users than among nonusers, while one multicountry trial found no differences in these parameters. Only one study demonstrated lower average weights during the first year of life for infants whose mothers used COCs while breastfeeding. None of the eight studies, four of which were observational, included in this review documented adverse infant health outcomes. CONCLUSIONS: Limited evidence demonstrates an inconsistent effect of COC on breastfeeding duration and success. The evidence is inadequate to determine whether a mother's use of these drugs affects breastfeeding duration or the infant's health. (C) 2010 Elsevier Inc. All rights reserved. |
Reservations concerning second-hand fentanyl exposure in the operating room
Law BF , Hettick JM , Hornsby-Myers J , Siegel PD . J Addict Dis 2010 29 (3) 282-3 We are aware of the controversy that Dr. Gold's report of trace levels of fentanyl and propofol in the air of surgical rooms has evoked.Citation1 , Citation2 , Citation3 , Citation4 Drug dependence among surgical and anesthesiology staff is a serious and complex issue, and we acknowledge the potential for generation of bioaerosol containing narcotics during surgery. Our study was an examination of room air during cardiovascular surgeries in a local hospital to quantify the level of “second hand” fentanyl,Citation 5 a similar setting to that previously reported.Citation 6 | Our findings are relevant to fentanyl only; we did not study or attempt to measure propofol. Our manuscript carefully detailed our sampling and analytical methodologies. We sampled an approximate 780-fold greater air volume and used instrumentation of equal sensitivity and better specificity to that reported by Dr. Gold. We are confident that if fentanyl-containing bioaerosol were present in the vicinity of the anesthesiology station at levels previously reported,Citation 5 we would have been able to quantify it. |
Laboratory evaluation of a physiologic sampling pump (PSP)
Lin MI , Groves WA , Freivalds A , Lee L , Lee EG , Slaven JE , Harper M . J Environ Monit 2010 12 (7) 1415-21 Recently, physiologic sampling pumps (PSPs), which can adjust their sampling rates in proportion to wearers' minute ventilation, have been proposed to better estimate exposure to airborne contaminants in the workplace. A laboratory evaluation was conducted to compare the performance of a new PSP with a traditional sampling pump (TSP) in an exposure chamber. Fifteen subjects (aged 19-36 years) performed two replicate sessions of step-tests for correlated and uncorrelated exposure scenarios on four separate days. When exposed to a scenario in which subject is highly correlated with m-xylene concentration over the sampling period (r = 0.93), the PSP-measured time-weighted average (TWA) concentrations are higher than TSP-measured concentrations (average ratio of PSP to TSP = 1.18). The ratio of PSP- and TSP-measured TWA concentrations for the uncorrelated scenario (r = 0.02) is closer to one, as expected, with an average value of 0.94. The test results of the linear mixed model further indicate that the performance of the PSP is unaffected by the anthropometric and physiological characteristics of the wearer. Potential differences in exposure estimates resulting from the use of the two instruments were examined in light of various schemes which can potentially occur in the field. With the capability of estimating the total volume of air inhaled over the sampling period with improved accuracy, PSPs show promise in reducing the inherent uncertainty in current risk assessment approaches that entail constant-flow (TSP) sampling approaches. |
Occupational exposure limits for nanomaterials: state of the art
Schulte P , Murashov V , Zumwalde R , Kuempel E , Geraci C . J Nanopart Res 2010 12 (6) 1971-1987 Assessing the need for and effectiveness of controlling airborne exposures to engineered nanomaterials in the workplace is difficult in the absence of occupational exposure limits (OELs). At present, there are practically no OELs specific to nanomaterials that have been adopted or promulgated by authoritative standards and guidance organizations. The vast heterogeneity of nanomaterials limits the number of specific OELs that are likely to be developed in the near future, but OELs could be developed more expeditiously for nanomaterials by applying dose–response data generated from animal studies for specific nanoparticles across categories of nanomaterials with similar properties and modes of action. This article reviews the history, context, and approaches for developing OELs for particles in general and nanoparticles in particular. Examples of approaches for developing OELs for titanium dioxide and carbon nanotubes are presented and interim OELs from various organizations for some nanomaterials are discussed. When adequate dose–response data are available in animals or humans, quantitative risk assessment methods can provide estimates of adverse health risk of nanomaterials in workers and, in conjunction with workplace exposure and control data, provide a basis for determining appropriate exposure limits. In the absence of adequate quantitative data, qualitative approaches to hazard assessment, exposure control, and safe work practices are prudent measures to reduce hazards in workers. |
Performance of high flow rate samplers for respirable particle collection
Lee T , Kim SW , Chisholm WP , Slaven J , Harper M . Ann Occup Hyg 2010 54 (6) 697-709 The American Conference of Governmental Industrial hygienists (ACGIH) lowered the threshold limit value (TLV) for respirable crystalline silica (RCS) exposure from 0.05 to 0.025 mg m(-3) in 2006. For a working environment with an airborne dust concentration near this lowered TLV, the sample collected with current standard respirable aerosol samplers might not provide enough RCS for quantitative analysis. Adopting high flow rate sampling devices for respirable dust containing silica may provide a sufficient amount of RCS to be above the limit of quantification even for samples collected for less than full shift. The performances of three high flow rate respirable samplers (CIP10-R, GK2.69, and FSP10) have been evaluated in this study. Eleven different sizes of monodisperse aerosols of ammonium fluorescein were generated with a vibrating orifice aerosol generator in a calm air chamber in order to determine the sampling efficiency of each sampler. Aluminum oxide particles generated by a fluidized bed aerosol generator were used to test (i) the uniformity of a modified calm air chamber, (ii) the effect of loading on the sampling efficiency, and (iii) the performance of dust collection compared to lower flow rate cyclones in common use in the USA (10-mm nylon and Higgins-Dewell cyclones). The coefficient of variation for eight simultaneous samples in the modified calm air chamber ranged from 1.9 to 6.1% for triplicate measures of three different aerosols. The 50% cutoff size ((50)d(ae)) of the high flow rate samplers operated at the flow rates recommended by manufacturers were determined as 4.7, 4.1, and 4.8 mum for CIP10-R, GK2.69, and FSP10, respectively. The mass concentration ratio of the high flow rate samplers to the low flow rate cyclones decreased with decreasing mass median aerodynamic diameter (MMAD) and high flow rate samplers collected more dust than low flow rate samplers by a range of 2-11 times based on gravimetric analysis. Dust loading inside the high flow rate samplers does not appear to affect the particle separation in either FSP10 or GK2.69. The high flow rate samplers overestimated compared to the International Standards Organization/Comite Europeen de Normalisation/ACGIH respirable convention [up to 40% at large MMAD (27.5 mum)] and could provide overestimated exposure data with the current flow rates. However, both cyclones appeared to be able to provide relatively unbiased assessments of RCS when their flow rates were adjusted. |
Preventing heat-related illness among agricultural workers
Jackson LL , Rosenberg HR . J Agromedicine 2010 15 (3) 200-15 Hyperthermia from exertion and environmental conditions during agricultural work manifests itself by various symptoms and may lead to death. From 1992 through 2006, 68 workers employed in crop production and related services died from heat-related illness. The crop worker fatality rate averaged 4 heat-related deaths per one million workers per year-20 times higher than the 0.2 rate for US civilian workers overall. Many of the agricultural workers who died were foreign-born. Foreign-born workers tend to have limited English language skills and often are not acclimatized to exertion in hot weather when beginning seasonal jobs. Increased recognition of heat hazards to agricultural workers, in particular, has stimulated concern among employers, workers, and public policy makers. California and Washington have led the nation in adopting workplace safety standards designed to prevent heat-related illnesses. These state regulations include new specific requirements for employer provision of drinking water, shade for rest or other sufficient means to recover from heat, worker and supervisor training, and written heat safety plans. Agricultural employers face practical challenges in fulfilling the purpose and complying with these standards. By their very nature the standards impose generic requirements in a broad range of circumstances and may not be equally protective in all agricultural work settings. It is vital that employers and supervisors have a thorough knowledge of heat illness prevention to devise and implement safety measures that suit local conditions. Ongoing risk-based assessment of current heat conditions by employers is important to this safety effort. Workers need training to avoid heat illness and recognize the symptoms in themselves and coworkers. Innovative management practices are joining time-honored approaches to controlling heat stress and strain. Research targeted to answer questions about heat accumulation and dissipation during agricultural work and audience-sensitive education to promote understanding of basic physiology and recognition of hyperthermia symptoms can aid in heat illness prevention. This review was prepared for the Agricultural Safety and Health Council of America/ National Institute for Occupational Safety and Health conference, "Be Safe, Be Profitable: Protecting Workers in Agriculture," Dallas/Fort Worth, Texas, January 27-28, 2010. |
Bridging gaps in agricultural safety and health
Conway GA . J Agromedicine 2010 15 (3) 180-3 This special issue consists of 11 papers documenting scientific and industry interactions from the first joint Agricultural Safety and Health Council of America/National Institute for Occupational Safety and Health conference, “Be Safe, Be Profitable: Protecting Workers in Agriculture,” held January 27–28, 2010, in Dallas/Fort Worth, Texas. These articles cover topics that were selected by the conference organizers as being of compelling interest to the community of public health, safety professionals, and agricultural producers with a shared interest in the safety and health of America's farmers and agricultural workers. | This innovative conference focused on uniting agricultural leaders, safety practitioners, researchers and farm workers in determining the best practices to improve health and safety of the agriculture workforce. The program featured eight expert panels and six plenary speakers to identify research gaps and promising interventions, and an interactive research networking reception to help plant seeds of collaboration among attendees. Reducing occupational injuries and illness in agriculture will be most effective with active cooperation among producers, researchers, and farm health and safety advocates. This conference represents an important step forward in fostering relationships among these groups. It is our hope that this pattern of cooperation and collaboration will continue beyond the length of the conference. What follows is a synopsis of some of the highpoints mentioned by speakers and panels, offered in hopes of stimulating your interest in reading each of the articles in toto. As space available for each article in this issue was limited, the reader may also want to follow along or refer to some of the speaker's slide set and video, posted at: http://www.ashca.com/, then browsing via the “2010 Conference” option. |
Proficiency testing of human leukocyte antigen-DR and human leukocyte antigen-DQ genetic risk assessment for type 1 diabetes using dried blood spots
Dantonio P , Meredith-Molloy N , Hagopian WA , She JX , Akolkar B , Cordovado SK , Hendrix M , Henderson LO , Hannon WH , Vogt RF . J Diabetes Sci Technol 2010 4 (4) 929-941 BACKGROUND: The plurality of genetic risk for developing type 1 diabetes mellitus (T1DM) lies within the genes that code for the human leukocyte antigens (HLAs). Many T1DM studies use HLA genetic risk assessment to identify higher risk individuals, and they often conduct these tests on dried blood spots (DBSs) like those used for newborn bloodspot screening. One such study is The Environmental Determinants of Diabetes in the Young (TEDDY), a long-term prospective study of environmental risk factors. To provide quality assurance for T1DM studies that employ HLA genetic risk assessment, the Centers for Disease Control and Prevention (CDC) conducts both a voluntary quarterly proficiency testing (VQPT) program available to any laboratory and a mandatory annual proficiency testing (PT) challenge for TEDDY laboratories. METHODS: Whole blood and DBS samples with a wide range of validated HLA-DR and HLA-DQ genotypes were sent to the participating laboratories. Results were evaluated on the basis of both the reported haplotypes and the HLA genetic risk assessment. RESULTS: Of the reported results from 24 panels sent out over six years in the VQPT, 94.7% (857/905) were correctly identified with respect to the relevant HLA-DR or HLA-DQ alleles, and 96.4% (241/250) were correctly categorized for risk assessment. Significant improvement was seen over the duration of this program, usually reaching 100% correct categorization during the last three years. Of 1154 reported results in four TEDDY PT challenges, 1153 (99.9%) were correctly identified for TEDDY eligibility. CONCLUSIONS: The different analytical methods used by T1DM research centers all provided accurate (>99%) results for genetic risk assessment. The two CDC PT programs documented the validity of the various approaches to screening and contributed to overall quality assurance. |
Commentary: The quest for weight standards
Flegal KM . Int J Epidemiol 2010 39 (4) 963-7 Symonds’ article1 presents a table of standard weights for height for men that were derived from 1897 life insurance data from the USA and Canada. As has been the case with other life insurance height–weight tables,2–8 it is not completely clear how Symonds’ table was derived and exactly what his standards represent. As noted by Rothstein,9 the goals of life insurance companies tend to be somewhat different to those of health researchers and include finding accurately and inexpensively measured factors with good predictive values rather than looking for causal factors. Characteristics such as sex, age, occupation and possibly even body weight, may be good predictors without being in themselves causes of mortality. For purposes of assessing causality in health research, life insurance data tend to have many limitations, including that they represent policies, not individuals (one individual may have more than one policy), that the data on weight and height are collected unsystematically, show some digit preference and may be self-reported rather than measured, and that the sample is highly selected. |
Personality features and personality disorders in chronic fatigue syndrome: A population-based study
Nater UM , Jones JF , Lin JM , Maloney E , Reeves WC , Heim C . Psychother Psychosom 2010 79 (5) 312-318 BACKGROUND: Chronic fatigue syndrome (CFS) presents unique diagnostic and management challenges. Personality may be a risk factor for CFS and may contribute to the maintenance of the illness. METHODS: 501 study participants were identified from the general population of Georgia: 113 people with CFS, 264 with unexplained unwellness but not CFS (insufficient fatigue, ISF) and 124 well controls. We used the Personality Diagnostic Questionnaire, 4th edition, to evaluate DSM-IV personality disorders. We used the NEO Five-Factor Inventory to assess personality features (neuroticism, extraversion, openness, agreeableness and conscientiousness). The Multidimensional Fatigue Inventory measured 5 dimensions of fatigue, and the Medical Outcomes Survey Short Form 36 measured 8 dimensions of functional impairment. RESULTS: Twenty-nine percent of the CFS cases had at least 1 personality disorder, compared to 28% of the ISF cases and 7% of the well controls. The prevalence of paranoid, schizoid, avoidant, obsessive-compulsive and depressive personality disorders were significantly higher in CFS and ISF compared to the well controls. The CFS cases had significantly higher scores on neuroticism, and significantly lower scores on extraversion than those with ISF or the well controls. Personality features were correlated with selected composite characteristics of fatigue. CONCLUSIONS: Our results suggest that CFS is associated with an increased prevalence of maladaptive personality features and personality disorders. This might be associated with being noncompliant with treatment suggestions, displaying unhealthy behavioral strategies and lacking a stable social environment. Since maladaptive personality is not specific to CFS, it might be associated with illness per se rather than with a specific condition. |
A Bayesian network model for biomarker-based dose response
Hack CE , Haber LT , Maier A , Shulte P , Fowler B , Lotz WG , Savage Jr RE . Risk Anal 2010 30 (7) 1037-51 A Bayesian network model was developed to integrate diverse types of data to conduct an exposure-dose-response assessment for benzene-induced acute myeloid leukemia (AML). The network approach was used to evaluate and compare individual biomarkers and quantitatively link the biomarkers along the exposure-disease continuum. The network was used to perform the biomarker-based dose-response analysis, and various other approaches to the dose-response analysis were conducted for comparison. The network-derived benchmark concentration was approximately an order of magnitude lower than that from the usual exposure concentration versus response approach, which suggests that the presence of more information in the low-dose region (where changes in biomarkers are detectable but effects on AML mortality are not) helps inform the description of the AML response at lower exposures. This work provides a quantitative approach for linking changes in biomarkers of effect both to exposure information and to changes in disease response. Such linkage can provide a scientifically valid point of departure that incorporates precursor dose-response information without being dependent on the difficult issue of a definition of adversity for precursors. |
Route of administration and dose escalation assessment of an adenovirus-based influenza A (H5N1) vaccine in chickens
Steitz J , Wagner RA , Bristol T , Gao W , Donis RO , Gambotto A . Clin Vaccine Immunol 2010 17 (9) 1467-72 Highly-pathogenic avian influenza virus (HPAI) causes one of the most economically devastating poultry diseases. A HPAI vaccine to prevent the disease in commercial and backyard birds must be effective, safe and inexpensive. Recently, we demonstrated the efficacy of an adenovirus-based influenza H5N1 HPAI vaccine (Ad5.HA) in chickens. To further evaluate the potential of the Ad5.HA vaccine and its cost-effectiveness, studies were performed to determine the minimal effective dose and optimal route of administration in chickens. A dose as low as 10(7)vp/chicken of adenovirus-based H5N1 vaccine was sufficient to generate a robust humoral immune response, which correlated with the previously reported level of protection. Several routes of administration were evaluated for optimal vaccine administration, including: intratracheal, conjunctival, subcutaneous and in ovo. However, only the subcutaneous route of immunization induced a satisfactory level of influenza specific antibodies. Importantly, these studies established that vaccine-induced immunity was cross-reactive against an H5N1 strain from a different clade, emphasizing the potential of cross-protection. Our results suggest that the Ad5.HA HPAI vaccine is safe and effective with the potential of cross-clade protection. The ease of manufacturing and cost-effectiveness makes Ad5.HA an excellent avian influenza vaccine candidate with the ability to protect poultry from HPAI infection. Considering the limitations of the influenza vaccine technology currently used for poultry applications, any effort aimed to overcome those limitations is highly significant. |
Surgical extraction of an intraocular infection of Parelaphostrongylus tenuis in a horse
Reinstein SL , Lucio-Forster A , Bowman DD , Eberhard ML , Hoberg EP , Pot SA , Miller PE . J Am Vet Med Assoc 2010 237 (2) 196-199 CASE DESCRIPTION: A 4-year-old Hanoverian gelding was evaluated because of a mobile worm-like structure in the right eye. CLINICAL FINDINGS: Ophthalmologic examination of the right eye revealed a white, thin, coiled, mobile parasite, which was presumed to be a nematode, located in the ventral portion of the anterior chamber of the eye; there also were vitreal strands located temporally and inferiorly near the margin of the pupil. Results of ophthalmologic examination of the left eye were unremarkable. TREATMENT AND OUTCOME: The horse was treated with a neomycin-polymyxin B-dexamethasone ophthalmic solution applied topically (1 drop, q 8 h) to the right eye and penicillin V potassium (22,000 U/kg [10,000 U/lb], IV, q 6 h). The horse was anesthetized. A stab incision was made in the cornea, and a viscoelastic agent was infused around the parasite. The parasite was extracted via the incision by use of an iris hook and tying forceps. The horse had an uncomplicated recovery from the procedure and retained vision in the right eye. Gross and microscopic examination was used to identify the parasite as an adult meta-strongyloid nematode consistent with a fully developed male Parelaphostrongylus tenuis. CLINICAL RELEVANCE: To the authors' knowledge, this is the first report of intraocular parelaphostrongylosis in a horse. This report provided evidence that vision could be retained after treatment for intraocular P tenuis infection in a horse. (J Am Vet Med Assoc 2010;237:196-199) |
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