The relative effects of abciximab and tirofiban on platelet inhibition and C-reactive protein during coronary intervention
Saltzman AJ , Mehran R , Hooper WC , Moses JW , Weisz G , Collins MB , Lansky AJ , Kreps EM , Leon MB , Stone GW , Dangas G . J Invasive Cardiol 2010 22 (1) 2-6 BACKGROUND: We sought to compare the efficacy of tirofiban and abciximab on platelet inhibition as well as their effects of platelet inhibition on C-reactive protein levels during percutaneous coronary intervention (PCI). METHODS: Using a randomized, double-blind study design, 95 consecutively eligible patients were randomized to receive either tirofiban or abciximab before undergoing native coronary artery revascularization with a stent. Clinical endpoints were death, nonfatal MI, target vessel revascularization (TVR) with coronary artery bypass grafting or PCI within 30 days of the study procedure. The medications were compared for differences in platelet aggregation as measured by a rapid function platelet assay, as well as measurements of the inflammatory marker C-reactive protein (CRP) at frequent intervals following drug administration during PCI. RESULTS: A total of 95 patients were randomized to abciximab (n = 44) or tirofiban (n= 51). There was no significant difference in platelet aggregation documented throughout the procedure (10-, 20-, 30-, 45-minute time points). In diabetic patients abciximab had significantly lower platelet inhibition as compared to tirofiban at 10 minutes (84.17 +/- 8.28% vs. 90.40 +/- 5.79%; p = 0.0097). Using a Spearman correlation coefficient model, hs-CRP demonstrated an inverse relationship with platelet inhibition over time (-0.7307, p = 0.0002) in patients treated with abciximab. CONCLUSION: There is no major difference in platelet inhibition between tirofiban and abciximab during PCI. In this study, tirofiban showed a greater inhibition in diabetic subsets at the first time point within PCI. Platelet inhibition may be inversely related to the levels of CRP during PCI. |
The health and economic burden of chronic diseases in North Carolina
Easley C , Petersen R , Holmes M . N C Med J 2010 71 (1) 92-5 As with other states, North Carolina’s population experiences high rates of certain chronic diseases. | Because a comprehensive assessment of the impact of preventable conditions on North Carolina can | be lengthy, in this article we focus on the economic effects of selected preventable illnesses resulting in | increased hospitalization. | In North Carolina, the direct medical costs related to tobacco use, physical inactivity, and inadequate | nutrition alone are estimated to be at least $6 billion per year.1 These direct costs are potentially avoidable | with changes in tobacco use, physical activity, and nutrition. One specific portion of the economic burden | of chronic diseases in North Carolina is apparent in the crude hospitalization rates for the selected | diagnosis codes at discharge for persons over 65 years old (see Table 1). Such persons will experience | the largest effects from changes in behavior related to tobacco use, physical inactivity, and inadequate | nutrition because North Carolina adults are somewhat more likely to smoke, have sedentary lifestyles, | and be obese.2 |
High adiposity and high body mass index-for-age in US children and adolescents overall and by race-ethnic group
Flegal KM , Ogden CL , Yanovski JA , Freedman DS , Shepherd JA , Graubard BI , Borrud LG . Am J Clin Nutr 2010 91 (4) 1020-6 BACKGROUND: Body mass index (BMI)-for-age has been recommended as a screening test for excess adiposity in children and adolescents. OBJECTIVE: We quantified the performance of standard categories of BMI-for-age relative to the population prevalence of high adiposity in children and adolescents overall and by race-ethnic group in a nationally representative US population sample by using definitions of high adiposity that are consistent with expert committee recommendations. DESIGN: Percentage body fat in 8821 children and adolescents aged 8-19 y was measured by using dual-energy X-ray absorptiometry in 1999-2004 as part of a health examination survey. RESULTS: With the use of several different cutoffs for percentage fat to define high adiposity, most children with high BMI-for-age (> or = 95th percentile of the growth charts) had high adiposity, and few children with normal BMI-for-age (<85th percentile) had high adiposity. The prevalence of high adiposity in intermediate BMI categories varied from 45% to 15% depending on the cutoff. The prevalence of a high BMI was significantly higher in non-Hispanic black girls than in non-Hispanic white girls, but the prevalence of high adiposity was not significantly different. CONCLUSIONS: Current BMI cutoffs can identify a high prevalence of high adiposity in children with high BMI-for-age and a low prevalence of high adiposity in children with normal BMI-for-age. By these adiposity measures, less than one-half of children with intermediate BMIs-for-age (85th to <95th percentile) have high adiposity. Differences in high BMI ranges between race-ethnic groups do not necessarily indicate differences in high adiposity. |
Association of testosterone and sex hormone-binding globulin with metabolic syndrome and insulin resistance in men
Li C , Ford ES , Li B , Giles WH , Liu S . Diabetes Care 2010 33 (7) 1618-24 Objective - We sought to assess the associations of testosterones and sex hormone-binding globulin (SHBG) with metabolic syndrome and insulin resistance in men. Research Design and Methods - We defined metabolic syndrome according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Among men aged ≥20 years who participated in the Third National Health and Nutrition Examination Survey (n=1,226), the Cox proportional hazard model was used to estimate the prevalence ratio (PR) and 95% confidence interval (CI) of metabolic syndrome according to circulating concentrations of testosterones and SHBG. Results - After adjustment for age, race/ethnicity, smoking status, alcohol intake, physical activity level, low-density lipoprotein cholesterol, C-reactive protein, and insulin resistance, men in the first quartile (lowest) (PR, 2.16; 95% CI, 1.53-3.06) and second quartile of total testosterone (PR, 2.51; 95% CI, 1.86-3.37) were more likely to have metabolic syndrome than men in the fourth quartile (highest, reference group) (P <0.001 for linear trend). Similarly, men in the first quartile of SHBG (PR, 2.17; 95% CI, 1.32-3.56) were more likely to have metabolic syndrome than men in the fourth quartile (P=0.02 for linear trend). No significant associations of calculated free testosterone (P=0.31 for linear trend) and bioavailable testosterone (P=0.11 for linear trend) with metabolic syndrome were detected after adjustment for all possible confounders. Conclusions - Low concentrations of total testosterone and SHBG were strongly associated with increased likelihood of having metabolic syndrome, independent of traditional cardiovascular risk factors and insulin resistance. |
Treatment of hepatitis C virus (HCV) infection in patients coinfected with HIV in the HIV Outpatient Study (HOPS), 1999-2007
Vellozzi C , Buchacz K , Baker R , Spradling PR , Richardson J , Moorman A , Tedaldi E , Durham M , Ward J , Brooks JT . J Viral Hepat 2010 18 (5) 316-24 Liver disease due to hepatitis C virus (HCV) infection is a leading cause of non-AIDS-related morbidity and mortality in patients infected with HIV. We assessed the frequency of and predictors for initiation of treatment for HCV infection among patients coinfected with HCV/HIV enrolled in the HIV Outpatient Study (HOPS) during 1999-2007. We included patients with confirmed HCV infection, at least 1 year of subsequent follow-up, and no evidence of prior HCV treatment. We assessed predictors of HCV treatment initiation using Cox proportional hazards analyses. During 1999-2007, 103 (20%) HOPS patients coinfected with HCV/HIV initiated HCV treatment during a median of 4.3 years of follow-up (interquartile range: 2.7, 6.7). In multivariable analysis, non-Hispanic black race/ethnicity (hazard ratio HR] 0.3; 95% confidence interval [CI] = 0.2, 0.6) was independently associated with a lower likelihood of HCV treatment. Elevated alanine aminotransferase (ALT; HR 3.5; 95% CI = 2.2, 5.6) and CD4+ cell count ≥500 cells/mm(3) (HR 1.8; 95% CI = 1.2, 2.8) at the start of observation were independently associated with higher likelihood of HCV treatment. For patients starting observation in 1999-2001, 2002-2004 and 2005-2007, 5%, 11% and 21% of patients initiated treatment during the first year of follow-up, respectively. Between 1999 and 2007, despite a stable low fraction of patients coinfected with HCV/HIV initiating treatment for HCV infection, an increasing proportion initiated treatment within the first year after the infection was confirmed. Treatment of HCV infection in patients coinfected with HCV/HIV should be considered a priority, given the increased risk of accelerated end-stage liver disease. |
Recall errors in a weekly survey of diarrhoea in Guatemala: determining the optimal length of recall
Zafar SN , Luby SP , Mendoza C . Epidemiol Infect 2010 138 (2) 264-9 We measured the recall error, optimal recall length and factors associated with diarrhoea in a weekly survey. Data was taken from a year-long randomized controlled trial in which characteristics of diarrhoeal episodes were recorded weekly. We labelled the recall period as days 1-6; day 1 being the day before the visit. Recall error was the percentage difference between the number of episodes reported to begin on a particular day and the mean for days 1 and 2. Generalized estimating equations were used to determine associations. Recall error was 37% on day 3 and 51% on day 5. The error was less in younger children (by 10%), severe episodes (by 29%) and when blood was present in the stool (by 18%). Diarrhoea was underreported when the recall period extended beyond 2 days. Surveys that use longer recall periods risk underestimating diarrhoea incidence and selectively capturing more severe episodes. |
Estimating the disease burden of pandemic (H1N1) 2009 virus infection in Hunter New England, Northern New South Wales, Australia, 2009
Dawood FS , Hope KG , Durrheim DN , Givney R , Fry AM , Dalton CB . PLoS One 2010 5 (3) e9880 INTRODUCTION: On May 26, 2009, the first confirmed case of Pandemic (H1N1) 2009 virus (pH1N1) infection in Hunter New England (HNE), New South Wales (NSW), Australia (population 866,000) was identified. We used local surveillance data to estimate pH1N1-associated disease burden during the first wave of pH1N1 circulation in HNE. METHODS: Surveillance was established during June 1-August 30, 2009, for: 1) laboratory detection of pH1N1 at HNE and NSW laboratories, 2) pH1N1 community influenza-like illness (ILI) using an internet survey of HNE residents, and 3) pH1N1-associated hospitalizations and deaths using respiratory illness International Classification of Diseases 10 codes at 35 HNE hospitals and mandatory reporting of confirmed pH1N1-associated hospitalizations and deaths to the public health service. The proportion of pH1N1 positive specimens was applied to estimates of ILI, hospitalizations, and deaths to estimate disease burden. RESULTS: Of 34,177 specimens tested at NSW laboratories, 4,094 (12%) were pH1N1 positive. Of 1,881 specimens from patients evaluated in emergency departments and/or hospitalized, 524 (26%) were pH1N1 positive. The estimated number of persons with pH1N1-associated ILI in the HNE region was 53,383 (range 37,828-70,597) suggesting a 6.2% attack rate (range 4.4-8.2%). An estimated 509 pH1N1-associated hospitalizations (range 388-630) occurred (reported: 184), and up to 10 pH1N1-associated deaths (range 8-13) occurred (reported: 5). The estimated case hospitalization ratio was 1% and case fatality ratio was 0.02%. DISCUSSION: The first wave of pH1N1 activity in HNE resulted in symptomatic infection in a small proportion of the population, and the number of HNE pH1N1-associated hospitalizations and deaths is likely higher than officially reported. |
Influenza epidemiology and characterization of influenza viruses in patients seeking treatment for acute fever in Cambodia
Blair PJ , Wierzba TF , Touch S , Vonthanak S , Xu X , Garten RJ , Okomo-Adhiambo MA , Klimov AI , Kasper MR , Putnam SD . Epidemiol Infect 2010 138 (2) 199-209 The epidemiology, symptomology, and viral aetiology of endemic influenza remain largely uncharacterized in Cambodia. In December 2006, we established passive hospital-based surveillance to identify the causes of acute undifferentiated fever in patients seeking healthcare. Fever was defined as tympanic membrane temperature >38 degrees C. From December 2006 to December 2008, 4233 patients were screened for influenza virus by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). Of these patients, 1151 (27.2%) were positive for influenza. Cough (68.8% vs. 50.5%, P < 0.0001) and sore throat (55.0% vs. 41.9%, P < 0.0001) were more often associated with laboratory-confirmed influenza-infected patients compared to influenza-negative enrollees. A clear influenza season was evident between July and December with a peak during the rainy season. Influenza A and B viruses were identified in 768 (66.3%) and 388 (33.7%) of the influenza-positive population (n = 1153), respectively. In December 2008, passive surveillance identified infection of the avian influenza virus H5N1 in a 19-year-old farmer from Kandal province who subsequently recovered. From a subset of diagnostic samples submitted in 2007, 15 A(H1N1), seven A(H3N2) and seven B viruses were isolated. The predominant subtype tested was influenza A(H1N1), with the majority antigenically related to the A/Solomon Island/03/2006 vaccine strain. The influenza A(H3N2) isolates and influenza B viruses analysed were closely related to A/Brisbane/10/2007 or B/Ohio/01/2005 (B/Victoria/2/87-lineage) vaccine strains, respectively. Phylogenetic analysis of the HA1 region of the HA gene of influenza A(H1N1) viruses demonstrated that the Cambodian isolates belonged to clade 2C along with representative H1N1 viruses circulating in SE Asia at the time. These viruses remained sensitive to oseltamivir. In total, our data suggest that viral influenza infections contribute to nearly one-fifth of acute febrile illnesses and demonstrate the importance of influenza surveillance in Cambodia. |
Assessing a multilevel model of young children's oral health with national survey data
Bramlett MD , Soobader MJ , Fisher-Owens SA , Weintraub JA , Gansky SA , Platt LJ , Newacheck PW . Community Dent Oral Epidemiol 2010 38 (4) 287-98 Objectives: To empirically test a multilevel conceptual model of children's oral health incorporating 22 domains of children's oral health across four levels: child, family, neighborhood and state. Data source: The 2003 National Survey of Children's Health, a module of the State and Local Area Integrated Telephone Survey conducted by the Centers for Disease Control and Prevention's National Center for Health Statistics, is a nationally representative telephone survey of caregivers of children. Study design: We examined child-, family-, neighborhood-, and state-level factors influencing parent's report of children's oral health using a multilevel logistic regression model, estimated for 26 736 children ages 1-5 years. Principal findings: Factors operating at all four levels were associated with the likelihood that parents rated their children's oral health as fair or poor, although most significant correlates are represented at the child or family level. Of 22 domains identified in our conceptual model, 15 domains contained factors significantly associated with young children's oral health. At the state level, access to fluoridated water was significantly associated with favorable oral health for children. Conclusions: Our results suggest that efforts to understand or improve children's oral health should consider a multilevel approach that goes beyond solely child-level factors. |
Assessment of risk factors for infantile cataracts using a case-control study National Birth Defects Prevention Study, 2000-2004
Prakalapakorn SG , Rasmussen SA , Lambert SR , Honein MA . Ophthalmology 2010 117 (8) 1500-5 OBJECTIVE: To identify risk factors for infantile cataracts of unknown etiology. DESIGN: Case-control study. PARTICIPANTS: Case infants (n = 152) and control infants (n = 4205) enrolled in the National Birth Defects Prevention Study for birth years 2000-2004. METHODS: Multivariate analysis was performed exploring associations for risk factors for bilateral and unilateral infantile cataracts of unknown etiology. MAIN OUTCOME MEASURES: Infantile cataracts of unknown etiology. RESULTS: Maternal interviews were completed for 43 case infants with bilateral and 109 with unilateral infantile cataracts of unknown etiology. Very low birth weight (<1500 g) was associated with both unilateral (adjusted odds ratio [OR], 6.0; 95% confidence interval [CI], 2.2-16.3) and bilateral (OR, 13.2; 95% CI, 4.2-41.1) cataracts, whereas low birth weight (1500-2499 g) was only associated with bilateral cataracts (OR, 3.3; 95% CI, 1.3-8.1). Infants with unilateral cataracts were more likely to be born to primigravid women (OR, 1.6; 95% CI, 1.0-2.7) than women with ≥2 previous pregnancies, although this was of borderline significance. Although not significant, effect estimates were elevated suggesting a possible association between unilateral cataracts and maternal substance abuse during pregnancy, and between bilateral cataracts and urinary tract infection during pregnancy and aspirin use during pregnancy. CONCLUSIONS: Very low birth weight is associated with both bilateral and unilateral cataracts, whereas low birth weight is associated with bilateral cataracts and primigravidity with unilateral cataracts. Other associations, although not statistically significant, suggest risk factors that merit further research. FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any of the materials discussed in this article. |
Sporadic Salmonella enterica serotype Javiana infections in Georgia and Tennessee: a hypothesis-generating study
Clarkson LS , Tobin-D'Angelo M , Shuler C , Hanna S , Benson J , Voetsch AC . Epidemiol Infect 2010 138 (3) 340-6 From 1996 to 2004, the incidence of Salmonella Javiana infections increased in FoodNet, the U.S. national active foodborne disease surveillance programme. Contact with amphibians and consumption of tomatoes have been associated with outbreaks of S. Javiana infection. To generate and test hypotheses about risk factors associated with sporadic S. Javiana infections, we interviewed patients with laboratory-confirmed S. Javiana infection identified in Georgia and Tennessee during August-October 2004. We collected data on food and water consumption, animal contact, and environmental exposure from cases. Responses were compared with population-based survey exposure data. Seventy-two of 117 identified S. Javiana case-patients were interviewed. Consumption of well water [adjusted odds ratio (aOR) 4.3, 95% confidence interval (CI) 1.6-11.2] and reptile or amphibian contact (aOR 2.6, 95% CI 0.9-7.1) were associated with infection. Consumption of tomatoes (aOR 0.5, 95% CI 0.3-0.9) and poultry (aOR 0.5, 95% CI 0.2-1.0) were protective. Our study suggests that environmental factors are associated with S. Javiana infections in Georgia and Tennessee. |
Epidemiology of seafood-associated infections in the United States
Iwamoto M , Ayers T , Mahon BE , Swerdlow DL . Clin Microbiol Rev 2010 23 (2) 399-411 Seafood is part of a healthful diet, but seafood consumption is not risk-free. Seafood is responsible for an important proportion of food-borne illnesses and outbreaks in the United States. Seafood-associated infections are caused by a variety of bacteria, viruses, and parasites; this diverse group of pathogens results in a wide variety of clinical syndromes, each with its own epidemiology. Some seafood commodities are inherently more risky than others, owing to many factors, including the nature of the environment from which they come, their mode of feeding, the season during which they are harvested, and how they are prepared and served. Prevention of seafood-associated infections requires an understanding not only of the etiologic agents and seafood commodities associated with illness but also of the mechanisms of contamination that are amenable to control. Defining these problem areas, which relies on surveillance of seafood-associated infections through outbreak and case reporting, can lead to targeted research and help to guide control efforts. Coordinated efforts are necessary to further reduce the risk of seafood-associated illnesses. Continued surveillance will be important to assess the effectiveness of current and future prevention strategies. |
Surveillance of transmitted HIV type 1 drug resistance in newly diagnosed HIV type 1-infected patients in Shandong Province, China
Zhang J , Kang D , Fu J , Sun X , Lin B , Bi Z , Nkengasong JN , Yang C . AIDS Res Hum Retroviruses 2010 26 (1) 99-103 A survey to measure transmitted HIV-1 drug resistance (DR) was conducted in 2006 following the World Health Organization threshold survey protocol. Dried blood spots (DBS) were prepared from 53 newly HIV-1-diagnosed patients. Protease and reverse transcriptase (RT) gene regions were sequenced using a broadly sensitive genotyping assay and analyses to identify DR mutations and determine phylogeny of the HIV-1 strains were conducted. Forty-six of the 47 successfully genotyped DBS had no transmitted DR mutations; one had an NNRTI mutation (K101E) in the RT region. Phylogenetic analyses revealed 21 (44.7%) were CRF01_AE, 9 (19.1%) B, 6 (12.8%) CRF07_BC, 3 (6.4%) each of CRF08_BC and C, and 2 (4.3%) B/C unique recombinant forms (URF). The remaining three were one each of A/B, A/C, and unclassifiable. Our analyses indicate that the prevalence of transmitted DR in this population is low and the HIV-1 epidemic in the area was characterized by multiple subtypes and recombinant forms. |
Multiple genetic backgrounds of the amplified Plasmodium falciparum multidrug resistance (pfmdr1) gene and selective sweep of 184F mutation in Cambodia
Vinayak S , Alam MT , Sem R , Shah NK , Susanti AI , Lim P , Muth S , Maguire JD , Rogers WO , Fandeur T , Barnwell JW , Escalante AA , Wongsrichanalai C , Ariey F , Meshnick SR , Udhayakumar V . J Infect Dis 2010 201 (10) 1551-60 BACKGROUND: The emergence of artesunate-mefloquine (AS+MQ)-resistant Plasmodium falciparum in the Thailand-Cambodia region is a major concern for malaria control. Studies indicate that copy number increase and key alleles in the pfmdr1 gene are associated with AS+MQ resistance. In the present study, we investigated evidence for a selective sweep around pfmdr1 because of the spread of adaptive mutation and/or multiple copies of this gene in the P. falciparum population in Cambodia. METHODS: We characterized 13 microsatellite loci flanking (+/-99 kb) pfmdr1 in 93 single-clone P. falciparum infections, of which 31 had multiple copies and 62 had a single copy of the pfmdr1 gene. RESULTS: Genetic analysis revealed no difference in the mean (+/- standard deviation) expected heterozygosity (H(e)) at loci around single ([Formula: see text]) and multiple ([Formula: see text]) copies of pfmdr1. Evidence of genetic hitchhiking with the selective sweep of certain haplotypes was seen around mutant (184F) pfmdr1 allele, irrespective of the copy number. There was an overall reduction of 28% in mean H(e) (+/-SD) around mutant allele ([Formula: see text]), compared with wild-type allele ([Formula: see text]). Significant linkage disequilibrium was also observed between the loci flanking mutant pfmdr1 allele. CONCLUSION: The 184F mutant allele is under selection, whereas amplification of pfmdr1 gene in this population occurs on multiple genetic backgrounds. |
Global impact of rotavirus vaccines
Tate JE , Patel MM , Steele AD , Gentsch JR , Payne DC , Cortese MM , Nakagomi O , Cunliffe NA , Jiang B , Neuzil KM , de Oliveira LH , Glass RI , Parashar UD . Expert Rev Vaccines 2010 9 (4) 395-407 The WHO has recently recommended the inclusion of rotavirus vaccine in the national immunization programs of all countries. In countries in the Americas, Europe and Australia that have adopted routine childhood immunization against rotavirus, significant reductions in the burden of severe childhood diarrhea have been observed. Besides protecting vaccinated children, disease rates also appear to be reduced in unvaccinated children, suggesting indirect benefits from vaccination (i.e., herd protection). Early clinical trial data from Africa and Asia are promising, and further efforts are needed to optimize the benefits of vaccination in developing countries where vaccines are likely to have their greatest impact. |
Serotype specific antisera for pneumococcal serogroup 6 serotypes 6A, 6B and 6C
Melnick N , Thompson TA , Beall BW . J Clin Microbiol 2010 48 (6) 2311-2 Streptococcus pneumoniae strains can express one of at least 92 capsular serotypes. To our knowledge, our laboratory is one of two that maintain antisera for resolution of the first 90 discovered pneumococcal serotypes (4; unpublished data). Recently, the evaluation of serogroup 6 isolates using monoclonal antibodies led to the discovery of the 91st serotype, 6C (7), which has become the prevalent invasive serogroup 6 serotype within the United States (2, 9). The pneumococcal 7-valent conjugate vaccine (PCV7) does not protect against it, and it is not included within the newly licensed 13-valent conjugate vaccine. In addition, serotype 6C carriage may also be common within PCV7-vaccinated populations (3). Prior to the discovery of serotype 6C, serotypes 6A and 6B were the 2 known serogroup 6 serotypes. CDC antisera for quellung-based resolution of serotypes 6A and 6B are designated as Danish factors 6b and 6c (DF-6b and DF-6c), respectively. Our original DF-6b antiserum was positive for both 6A and 6C serotypes, preventing their resolution (Table (Table11). |
Population structure of a hybrid clonal group of methicillin-resistant Staphylococcus aureus, ST239-MRSA-III
Smyth DS , McDougal LK , Gran FW , Manoharan A , Enright MC , Song JH , de Lencastre H , Robinson DA . PLoS One 2010 5 (1) e8582 The methicillin-resistant Staphylococcus aureus (MRSA) clonal group known as ST239-MRSA-III is notable for its hybrid origin and for causing sustained hospital epidemics worldwide since the late 1970s. We studied the population structure of this MRSA clonal group using a sample of 111 isolates that were collected over 34 years from 29 countries. Genetic variation was assessed using typing methods and novel ascertainment methods, resulting in approximately 15 kb of sequence from 32 loci for all isolates. A single most parsimonious tree, free of homoplasy, partitioned 28 haplotypes into geographically-associated clades, including prominent European, Asian, and South American clades. The rate of evolution was estimated to be approximately 100x faster than standard estimates for bacteria, and dated the most recent common ancestor of these isolates to the mid-20th century. Associations were discovered between the ST239 phylogeny and the ccrB and dru loci of the methicillin resistance genetic element, SCCmec type III, but not with the accessory components of the element that are targeted by multiplex PCR subtyping tools. In summary, the evolutionary history of ST239 can be characterized by rapid clonal diversification that has left strong evidence of geographic and temporal population structure. SCCmec type III has remained linked to the ST239 chromosome during clonal diversification, but it has undergone homoplasious losses of accessory components. These results provide a population genetics framework for the precise identification of emerging ST239 variants, and invite a re-evaluation of the markers used for subtyping SCCmec. |
Effect of body mass index and total blood volume on serum cotinine levels among cigarette smokers: NHANES 1999-2008
Jain RB , Bernert JT . Clin Chim Acta 2010 411 1063-8 INTRODUCTION: Body mass index (BMI) and total blood volume are not always considered as variables that affect serum cotinine concentrations. METHOD: We used data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999-2008 and fitted regression models for smokers. In addition to traditionally used covariates like age, race, gender, and average number of cigarettes smoked daily, we used BMI and total blood volume (TBV) as continuous variables to evaluate the impact of these variables on serum cotinine levels. RESULTS: Adjusted serum cotinine levels increased statistically significantly with increase in age (p<0.001). Serum cotinine levels increased statistically significantly (p<0.001) with average number of cigarettes smoked daily. Levels of adjusted serum concentrations from high to low by race/ethnicity were: non-Hispanic blacks, non-Hispanic whites, other race/ethnicity, and Mexican-Americans; and all differences were statistically significant. A model of serum cotinine including BMI without TBV found BMI to be a significant predictor (p<0.001) and similarly a model including TBV without BMI found TBV to be a significant predictor (p<0.001). When BMI and TBV were both included in the model, the significance of BMI changed markedly (p=0.93) with substantive changes in the BMI coefficient and the significance of TBV changed also (p=.024) with small change in the TBV coefficient. DISCUSSION: TBV and BMI are significant predictors of serum cotinine concentrations. TBV or BMI, but not both, should be included in predictive models of serum cotinine concentrations. |
Adipose tissue serves as a reservoir for recrudescent Rickettsia prowazekii infection in a mouse model
Bechah Y , Paddock CD , Capo C , Mege JL , Raoult D . PLoS One 2010 5 (1) e8547 Brill-Zinsser disease, the relapsing form of epidemic typhus, typically occurs in a susceptible host years or decades after the primary infection; however, the mechanisms of reactivation and the cellular reservoir during latency are poorly understood. Herein we describe a murine model for Brill-Zinsser disease, and use PCR and cell culture to show transient rickettsemia in mice treated with dexamethasone >3 months after clinical recovery from the primary infection. Treatment of similarly infected mice with cyclosporine failed to produce recrudescent bacteremia. Therapy with doxycycline for the primary infection prevented recrudescent bacteremia in most of these mice following treatment with dexamethasone. Rickettsia prowazekii (the etiologic agent of epidemic typhus) was detected by PCR, cell culture, and immunostaining methods in murine adipose tissue, but not in liver, spleen, lung, or central nervous system tissues of mice 4 months after recovery from the primary infection. The lungs of dexamethasone-treated mice showed impaired expression of beta-defensin transcripts that may be involved in the pathogenesis of pulmonary lesions. In vitro, R. prowazekii rickettsiae infected and replicated in the murine adipocyte cell line 3T3-L1. Collectively these data suggest a role for adipose tissue as a potential reservoir for dormant infections with R. prowazekii. |
Bifunctional polymeric inhibitors of human influenza A viruses
Haldar J , Alvarez de Cienfuegos L , Tumpey TM , Gubareva LV , Chen J , Klibanov AM . Pharm Res 2010 27 (2) 259-63 PURPOSE: New antiviral agents were prepared by attaching derivatives of sialic acid (1) and of the drug zanamivir (2) to poly(isobutylene-alt-maleic anhydride) (poly-(1 + 2)) or by mixing poly-1 and poly-2, followed by assaying them against wild-type and drug-resistant influenza A Wuhan viruses. METHODS: Individually or together, 1 and 2 were covalently bonded to the polymer. The antiviral potencies of the resultant poly-1, poly-2, poly-(1 + 2), and poly-1 + poly-2, as well as 1 and 2, were assessed using plaque reduction assay. RESULTS: Attaching 1 to the polymer improved at best millimolar IC(50) values over three orders of magnitude. While 2 exhibited micromolar IC(50) values, poly-2 was >100-fold even more potent. The IC(50) of poly-(1 + 2) against the wild-type strain was >300-fold and approximately 17-fold better than of poly-1 and poly-2, respectively. In contrast, the potency of poly-(1 + 2) vs. poly-2 against the mutant strain merely doubled. The mixture of poly-1 + poly-2 inhibited both viral strains similarly to poly-2. CONCLUSIONS: The bifunctional poly-(1 + 2) acts synergistically against the wild-type influenza virus, but not against its drug-resistant mutant, as compared to a physical mixture of the monofunctional poly-1 and poly-2. |
Dosage comparison of Congo Basin and West African strains of monkeypox virus using a prairie dog animal model of systemic orthopoxvirus disease
Hutson CL , Carroll DS , Self J , Weiss S , Hughes CM , Braden Z , Olson VA , Smith SK , Karem KL , Regnery RL , Damon IK . Virology 2010 402 (1) 72-82 The prairie dog is valuable for the study of monkeypox virus (MPXV) virulence and closely resembles human systemic orthopoxvirus disease. Herein, we utilize a variable dose intranasal challenge with approximately 10(3), 10(4), 10(5), and 10(6)PFU for each clade to further characterize virulence differences between the two MPXV clades. A trend of increased morbidity and mortality as well as greater viral shedding was observed with increasing viral challenge dose. Additionally, there appeared to be a delay in onset of disease for animals challenged with lower dosages of virus. Mathematical calculations were used to determine LD(50) values and based on these calculations, Congo Basin MPXV had approximately a hundred times lower LD(50) value than the West African clade (5.9x10(3) and 1.29x10(5) respectively); reinforcing previous findings that Congo Basin MPXV is more virulent. |
Intermittent preventive treatment in infants for the prevention of malaria in rural Western Kenya: a randomized, double-blind placebo-controlled trial
Odhiambo FO , Hamel MJ , Williamson J , Lindblade K , ter Kuile FO , Peterson E , Otieno P , Kariuki S , Vulule J , Slutsker L , Newman RD . PLoS One 2010 5 (4) e10016 BACKGROUND: Intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) for the prevention of malaria has shown promising results in six trials. However, resistance to SP is rising and alternative drug combinations need to be evaluated to better understand the role of treatment versus prophylactic effects. METHODS: Between March 2004 and March 2008, in an area of western Kenya with year round malaria transmission with high seasonal intensity and high usage of insecticide-treated nets, we conducted a randomized, double-blind placebo-controlled trial with SP plus 3 days of artesunate (SP-AS3), 3 days of amodiaquine-artesunate (AQ3-AS3), or 3 days of short-acting chlorproguanil-dapsone (CD3) administered at routine expanded programme of immunization visits (10 weeks, 14 weeks and 9 months). PRINCIPAL FINDINGS: 1,365 subjects were included in the analysis. The incidence of first or only episode of clinical malaria during the first year of life (primary endpoint) was 0.98 episodes/person-year in the placebo group, 0.74 in the SP-AS3 group, 0.76 in the AQ3-AS3 group, and 0.82 in the CD3 group. The protective efficacy (PE) and 95% confidence intervals against the primary endpoint were: 25.7% (6.3, 41.1); 25.9% (6.8, 41.0); and 16.3% (-5.2, 33.5) in the SP-AS3, AQ3-AS3, and CD3 groups, respectively. The PEs for moderate-to-severe anaemia were: 27.5% (-6.9, 50.8); 23.1% (-11.9, 47.2); and 11.4% (-28.6, 39.0). The duration of the protective effect remained significant for up to 5 to 8 weeks for SP-AS3 and AQ3-AS3. There was no evidence for a sustained beneficial or rebound effect in the second year of life. All regimens were well tolerated. CONCLUSIONS: These results support the view that IPTi with long-acting regimens provide protection against clinical malaria for up to 8 weeks even in the presence of high ITN coverage, and that the prophylactic rather than the treatment effect of IPTi appears central to its protective efficacy. |
A proposal for a common nomenclature for viral clades that form the species varicella-zoster virus: summary of VZV Nomenclature Meeting 2008, Barts and the London School of Medicine and Dentistry, 24-25 July 2008
Breuer J , Grose C , Norberg P , Tipples G , Schmid DS . J Gen Virol 2010 91 821-8 Varicella-zoster virus (VZV), the cause of chickenpox and zoster, was the first human herpesvirus to be sequenced fully and the first for which vaccines have been licensed and widely used. Three groups have published genotyping schemes based on single nucleotide polymorphisms (SNPs) and, between them, have identified five distinct phylogenetic clades, with an additional two putative clades. Sequencing of over 23 whole VZV genomes from around the world further refined the phylogenetic distinctions between SNP genotypes. Widespread surveillance in countries in which the varicella vaccine is now in use and the difficulties posed by three unique genotyping approaches prompted an international meeting, at which a common nomenclature based on phylogenetic clades was agreed upon. In this paper, we review the original genotyping schemes and discuss the basis for a novel common nomenclature for VZV strains. We propose a minimum set of SNPs that we recommend should be used to genotype these viruses. Finally, we suggest criteria by which novel clades can be recognized. |
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