Urinary naphthol metabolites and chromosomal aberrations in 5-year-old children.
Orjuela MA , Liu X , Miller RL , Warburton D , Tang D , Jobanputra V , Hoepner L , Suen IH , Diaz-Carreno S , Li Z , Sjodin A , Perera FP . Cancer Epidemiol Biomarkers Prev 2012 21 (7) 1191-202 BACKGROUND: Exposure to naphthalene, an International Agency for Research on Cancer (IARC)-classified possible carcinogen and polycyclic aromatic hydrocarbon (PAH), is widespread, though resulting health effects are poorly understood. Metabolites of naphthalene, 1- and 2-naphthol, are measurable in urine and are biomarkers of personal exposure. Chromosomal aberrations, including translocations, are established markers of cancer risk and a biodosimeter of clastogenic exposures. Although prenatal (maternal) PAH exposure predicts chromosomal aberrations in cord blood, few studies have examined chromosomal aberrations in school-age children and none has examined their association with metabolites of specific PAHs. METHODS: Using Whole Chromosome Paint Fluorescent in situ Hybridization, we documented chromosomal aberrations including translocations, in 113 five-year-old urban minority children and examined their association with concurrent concentrations of PAH metabolites measured in urine. RESULTS: We report that in lymphocytes, the occurrence and frequency of chromosomal aberrations including translocations are associated with levels of urinary 1- and 2-naphthol. When doubling the levels of urinary naphthols, gender-adjusted OR for chromosomal aberrations are 1.63 [95% confidence interval (CI), 1.21-2.19] and 1.44 (95% CI, 1.02-2.04) for 1- and 2-naphthol, respectively; and for translocations OR = 1.55 (95% CI, 1.11-2.17) and 1.92 (95% CI, 1.20-3.08) for 1- and 2-naphthol, respectively. CONCLUSION: Our results show that markers of exposure to naphthalene in children are associated with translocations in a dose-related manner, and that naphthalene may be a clastogen. IMPACT: Indoor exposure to elevated levels of naphthalene is prevalent in large regions of the world. This study is the first to present an association between a marker of naphthalene exposure and a precarcinogenic effect in humans. (Cancer Epidemiol Biomarkers Prev; 21(7); 1191-202. (c)2012 AACR.) |
Health utility scores for people with type 2 diabetes in U.S. managed care health plans: results from Translating Research Into Action for Diabetes (TRIAD)
Zhang P , Brown MB , Bilik D , Ackermann RT , Li R , Herman WH . Diabetes Care 2012 35 (11) 2250-6 OBJECTIVE: To estimate the health utility scores associated with type 2 diabetes, its treatments, complications, and comorbidities. RESEARCH DESIGN AND METHODS: We analyzed health-related quality-of-life data, collected at baseline during Translating Research Into Action for Diabetes, a multicenter, prospective, observational study of diabetes care in managed care, for 7,327 individuals with type 2 diabetes. We measured quality-of-life using the EuroQol (EQ)-5D, a standardized instrument for which 1.00 indicates perfect health. We used multivariable regression to estimate the independent impact of demographic characteristics, diabetes treatments, complications, and comorbidities on health-related quality-of-life. RESULTS: The mean EQ-5D-derived heath utility score for those individuals with diabetes was 0.80. The modeled utility score for a nonobese, non-insulin-treated, non-Asian, non-Hispanic man with type 2 diabetes, with an annual household income of more than $40,000, and with no diabetes complications, risk factors for cardiovascular disease, or comorbidities, was 0.92. Being a woman, being obese, smoking, and having a lower household income were associated with lower utility scores. Arranging complications from least to most severe according to the reduction in health utility scores resulted in the following order: peripheral vascular disease, other heart diseases, transient ischemic attack, cerebral vascular accident, nonpainful diabetic neuropathy, congestive heart failure, dialysis, hemiplegia, painful neuropathy, and amputation. CONCLUSIONS: Major diabetes complications and comorbidities are associated with decreased health-related quality-of-life. Utility estimates from our study can be used to assess the impact of diabetes on quality-of-life and conduct cost-utility analyses. |
Scale-up of isoniazid preventive therapy in PEPFAR-assisted clinical sites in South Africa
Bristow CC , Larson E , Vilakazi-Nhlapo AK , Wilson M , Klausner JD . Int J Tuberc Lung Dis 2012 16 (8) 1020-2 We reviewed the implementation of isoniazid preventive therapy (IPT) in South Africa from January 2010 to March 2011. The South African National Department of Health distributed revised IPT guidelines in May 2010 to increase IPT use in eligible human immunodeficiency virus (HIV) infected patients. We found a dramatic increase in the absolute numbers of patients reported to have been initiated on IPT (from 3309 in January-March 2010 to 49,130 in January-March 2011), representing an increase in the proportion (1.0-10.5%) of potentially eligible HIV-infected patients started on IPT. |
Lessons learned during tuberculosis screening in public medical clinics in Francistown, Botswana
Bloss E , Makombe R , Kip E , Smit M , Chirenda J , Gammino VM , Creek T , Oeltmann JE . Int J Tuberc Lung Dis 2012 16 (8) 1030-2 In Botswana, where one quarter of the adult population is infected with the human immunodeficiency virus and the annual tuberculosis (TB) incidence is among the highest globally, intensified TB case finding is needed in health care facilities to detect and treat TB cases early and prevent transmission. During August-December 2009, TB screening was implemented among adults at patient intake in five clinics in Francistown. Among 11,779 TB screenings at intake, 926 were positive. Nineteen patients were diagnosed with TB. Routine TB screening at intake was operationally feasible, but had low yield. Innovative case-finding strategies are needed in Botswana. |
Outcomes and follow-up of patients treated for multidrug-resistant tuberculosis in Orel, Russia, 2002-2005
Cavanaugh JS , Kazennyy BY , Nguyen ML , Kiryanova EV , Vitek E , Khorosheva TM , Nemtsova E , Cegielski JP . Int J Tuberc Lung Dis 2012 16 (8) 1069-74 SETTING: Multidrug-resistant tuberculosis (MDR-TB) treatment facility, Orel Oblast, Russian Federation. OBJECTIVES: To determine factors associated with poor outcome and to document status of patients after recording of TB outcomes. DESIGN: Retrospective review of prospective single cohort. RESULTS: Among 192 patients, factors significantly associated with poor outcome in multivariate analysis include three or more treatment interruptions during the intensive phase of therapy and alcohol or drug addiction (adjusted OR [aOR] 2.1, 95%CI 1.0-4.3 and aOR 1.9, 95%CI 1.0-3.7). Previous treatment was associated with poor outcome, but only among smear-positive patients (aOR 3.1, 95%CI 1.3-7.3). Ten patients (5%) developed extensively drug-resistant TB (XDR-TB) during treatment; of 115 patients with at least 6 months of follow-up data after outcomes were recorded, 13 (11%) developed XDR-TB. CONCLUSION: Interventions focused on supporting patient adherence during the intensive phase of treatment; the management of drug and alcohol addiction should be developed and studied. A substantial proportion of patients developed XDR-TB during and after treatment. Longer term follow-up data of patients treated for MDR-TB are needed to better inform programmatic policy. |
Predictors of failure in timely tuberculosis treatment completion, United States
Mitruka K , Winston CA , Navin TR . Int J Tuberc Lung Dis 2012 16 (8) 1075-82 SETTING: The US tuberculosis (TB) surveillance system. OBJECTIVE: To examine failure in timely TB treatment completion to identify interventions toward achieving the national goal of ≥93% treatment completion in ≤12 months among patients eligible for 6-9 month regimens. DESIGN: We examined 1993-2006 trends in timely treatment completion; for 2006 cases, we used Poisson regression to assess predictors for failure in timely completion. RESULTS: Timely treatment completion improved from 64% in 1993 to 84% in 2006, with similar trends among foreign- and US-born persons and racial/ethnic subgroups. Annual increases in timely completion were ≤1 percentage point during 1998-2006. Subpopulations at highest risk for failure in timely completion were persons with combined pulmonary and extra-pulmonary disease (foreign-born adjusted RR [aRR] 3.25, 95%CI 2.47-4.28; US-born aRR 2.75, 95%CI 1.98-3.83) or incarceration (foreign-born aRR 2.30, 95%CI 1.80-2.93; US-born aRR 1.71, 95%CI 1.36-2.14). Homelessness and human immunodeficiency virus infection were other risk factors. CONCLUSIONS: Particular attention to timely completion is needed for subpopulations requiring strong medical expertise in TB management and those at risk for treatment non-adherence, especially if foreign-born. Understanding and addressing causes of delayed completion and improving documentation of treatment completion among all cases will be crucial to achieving the US goal. |
Q fever with unusual exposure history: a classic presentation of a commonly misdiagnosed disease
Nett RJ , Book E , Anderson AD . Case Rep Infect Dis 2012 2012 916142 We describe the case of a man presumptively diagnosed and treated for Rocky Mountain spotted fever following exposure to multiple ticks while riding horses. The laboratory testing of acute and convalescent serum specimens led to laboratory confirmation of acute Q fever as the etiology. This case represents a potential tickborne transmission of Coxiella burnetii and highlights the importance of considering Q fever as a possible diagnosis following tick exposures. |
Factors associated with delays in treatment initiation after tuberculosis diagnosis in two districts of India
Paul D , Busireddy A , Nagaraja SB , Satyanarayana S , Dewan PK , Nair SA , Sarkar S , Ahmed QT , Sarkar S , Shamrao SR , Harries AD , Oeltmann JE . PLoS One 2012 7 (7) e39040 BACKGROUND: Excessive time between diagnosis and initiation of tuberculosis (TB) treatment contributes to ongoing TB transmission and should be minimized. In India, Revised National TB Control Programme (RNTCP) focuses on indicator start of treatment within 7 days of diagnosis for patients with sputum smear-positive PTB for monitoring DOTS implementation. OBJECTIVES: To determine length of time between diagnosis and initiation of treatment and factors associated with delays of more than 7 days in smear-positive pulmonary TB. METHODS: Using existing programme records such as the TB Register, treatment cards, and the laboratory register, we conducted a retrospective cohort study of all patients with smear-positive pulmonary TB registered from July-September 2010 in two districts in India. A random sample of patients with pulmonary TB who experienced treatment delay of more than 7 days was interviewed using structured questionnaire. RESULTS: 2027 of 3411 patients registered with pulmonary TB were smear-positive. 711(35%) patients had >7 days between diagnosis and treatment and 262(13%) had delays >15 days. Mean duration between TB diagnosis and treatment initiation was 8 days (range = 0-128 days). Odds of treatment delay >7 days was 1.8 times more likely among those who had been previously treated (95% confidence interval [CI] 1.5-2.3) and 1.6 (95% CI 1.3-1.8) times more likely among those diagnosed in health facilities without microscopy centers. The main factors associated with a delay >7 days were: patient reluctance to start a re-treatment regimen, patients seeking second opinions, delay in transportation of drugs to the DOT centers and delay in initial home visits. To conclude, treatment delay >7 days was associated with a number of factors that included history of previous treatment and absence of TB diagnostic services in the local health facility. Decentralized diagnostic facilities and improved referral procedures may reduce such treatment delays. |
Factors related to increasing prevalence of resistance to ciprofloxacin and other antimicrobial drugs in Neisseria gonorrhoeae, United States
Goldstein E , Kirkcaldy RD , Reshef D , Berman S , Weinstock H , Sabeti P , Del Rio C , Hall G , Hook EW , Lipsitch M . Emerg Infect Dis 2012 18 (8) 1290-7 Using data from the Gonococcal Isolate Surveillance Project, we studied changes in ciprofloxacin resistance in Neisseria gonorrhoeae isolates in the United States during 2002-2007. Compared with prevalence in heterosexual men, prevalence of ciprofloxacin-resistant N. gonorrhoeae infections showed a more pronounced increase in men who have sex with men (MSM), particularly through an increase in prevalence of strains also resistant to tetracycline and penicillin. Moreover, that multidrug resistance profile among MSM was negatively associated with recent travel. Across the surveillance project sites, first appearance of ciprofloxacin resistance in heterosexual men was positively correlated with such resistance for MSM. The increase in prevalence of ciprofloxacin resistance may have been facilitated by use of fluoroquinolones for treating gonorrhea and other conditions. The prominence of multidrug resistance suggests that using other classes of antimicrobial drugs for purposes other than treating gonorrhea helped increase the prevalence of ciprofloxacin-resistant strains that are also resistant to those drugs. |
Frontiers in cancer epidemiology: a challenge to the research community from the Epidemiology and Genomics Research Program at the National Cancer Institute.
Khoury MJ , Freedman AN , Gillanders EM , Harvey CE , Kaefer C , Reid BC , Rogers S , Schully SD , Seminara D , Verma M . Cancer Epidemiol Biomarkers Prev 2012 21 (7) 999-1001 The Epidemiology and Genomics Research Program (EGRP) at the National Cancer Institute (NCI) is developing scientific priorities for cancer epidemiology research in the next decade. We would like to engage the research community and other stakeholders in a planning effort that will include a workshop in December 2012 to help shape new foci for cancer epidemiology research. To facilitate the process of defining the future of cancer epidemiology, we invite the research community to join in an ongoing web-based conversation at http://blog-epi.grants.cancer.gov/ to develop priorities and the next generation of high-impact studies. (Cancer Epidemiol Biomarkers Prev; 21(7); 999-1001. (c)2012 AACR.) |
Unexplained death due to possible infectious diseases in infants-United States, 2006
Taylor CA , Holman RC , Callinan LS , Zaki SR , Blau DM . J Pediatr 2012 162 (1) 195-201 e3 OBJECTIVES: To quantify and examine factors related to unexplained death due to possible infectious causes (UDPIC) in infants and to analyze the associations between these factors in unexplained deaths and infants with fatal and nonfatal outcomes. STUDY DESIGN: Infant deaths meeting the International Classification of Diseases, Tenth Revision code inclusion and exclusion criteria for UDPIC were selected from the 2006 US Linked Birth and Infant Death data set. Two control groups of surviving and nonsurviving infants were selected and compared with the infants with UDPIC using a case-control study design with multivariate logistic regression models stratified by birth weight category. Comparisons with infants with identified infectious causes of death were also made. RESULTS: During 2006, 3570 infant deaths (12.5% of all US infant deaths) were categorized as a UDPIC. The highest rates for these unexplained infants deaths were found in blacks and American Indians/Alaska Natives. Infants of black mothers were more likely to experience UDPIC. Birth weight was a significant effect modifier in these models. CONCLUSIONS: Many factors may contribute to an infant's death being classified as a UDPIC, including race and marital status. Other factors, such as Hispanic ethnicity and maternal age, also may play a role. Infant characteristics, such as birth weight, may be related to factors that influence the decision not to conduct a postmortem examination in infant death cases. Additional research is needed to determine the true extent of infectious disease and its relationship to UDPIC in infants. |
Use of lung cancer screening tests in the United States: results from the 2010 National Health Interview Survey
Doria-Rose VP , White MC , Klabunde CN , Nadel MR , Richards TB , McNeel TS , Rodriguez JL , Marcus PM . Cancer Epidemiol Biomarkers Prev 2012 21 (7) 1049-59 BACKGROUND: Before evidence of efficacy, lung cancer screening was being ordered by many physicians. The National Lung Screening Trial (NLST), which showed a 20% reduction in lung cancer mortality among those randomized to receive low-dose computed tomography (LDCT), will likely lead to increased screening use. METHODS: We estimated the prevalence of chest X-ray and CT use in the United States using data from the 2010 National Health Interview Survey (NHIS). Subjects included 15,537 NHIS respondents aged ≥40 years without prior diagnosis of lung cancer. Estimates of the size of the U. S. population by age and smoking status were calculated. Multivariate logistic regression examined predictors of test use adjusting for potential confounders. RESULTS: Twenty-three percent of adults reported chest X-ray in the previous year and 2.5% reported chest X-ray specifically to check for lung cancer; corresponding numbers for chest CT were 7.5% and 1.3%. Older age, black race, male gender, smoking, respiratory disease, personal history of cancer, and having health insurance were associated with test use. Approximately, 8.7 million adults in the United States would be eligible for LDCT screening according to NLST eligibility criteria. CONCLUSIONS AND IMPACT: Monitoring of trends in the use of lung screening tests will be vital to assess the impact of NLST and possible changes in lung cancer screening recommendations and insurance coverage in the future. Education of patients by their physicians, and of the general public, may help ensure that screening is used appropriately, in those most likely to benefit. (Cancer Epidemiol Biomarkers Prev; 21(7); 1049-59. (c)2012 AACR.) |
Development of a new platform for neglected tropical disease surveillance
Lammie PJ , Moss DM , Brook Goodhew E , Hamlin K , Krolewiecki A , West SK , Priest JW . Int J Parasitol 2012 42 (9) 797-800 An expanded global focus on the control and elimination of neglected tropical diseases (NTDs) has called attention to the need to develop and validate surveillance strategies that are cost effective and can be integrated across diseases. Here, we describe a multiplex tool for the sensitive detection of antibody responses to NTDs as well as vaccine preventable diseases, malaria, and waterborne and zoonotic infections. The assay platform is robust, can be performed with either serum or dried blood spots and can be adapted to local epidemiological conditions and public health priorities. Multiplex assays open the door to conducting routine serosurveillance for NTDs through demographic health surveillance or malaria indicator surveys. |
Drug coverage surveys for neglected tropical diseases: 10 years of field experience
Worrell C , Mathieu E . Am J Trop Med Hyg 2012 87 (2) 216-22 Mass drug administration is one of the public health strategies recommended by the World Health Organization for the control and elimination of seven neglected tropical diseases (NTDs). Because adequate coverage is vital to achieve program goals, periodically conducting surveys to validate reported coverage to guide NTD programs is recommended. Over the past decade, the Centers for Disease Control and Prevention (CDC) and collaborators conducted more than 30 two-stage cluster household surveys across three continents. The questionnaires gathered coverage data and information relevant to improving NTD programs including NTD-related attitudes and practices. From the 37 coverage survey estimates obtained in those surveys, 73.3% indicated an over reporting of coverage, including all three that assessed school-based distributions. It took an average of 1 week to conduct a survey. Our experiences led us to conclude that coverage surveys are useful and feasible tools to ensure NTD elimination and control goals are reached. |
Outbreak of human trichinellosis in Northern California caused by Trichinella murrelli
Hall RL , Lindsay A , Hammond C , Montgomery SP , Wilkins PP , da Silva AJ , McAuliffe I , de Almeida M , Bishop H , Mathison B , Sun B , Largusa R , Jones JL . Am J Trop Med Hyg 2012 87 (2) 297-302 In October of 2008, an outbreak of trichinellosis occurred in northern California that sickened 30 of 38 attendees of an event at which meat from a black bear was served. Morphologic and molecular testing of muscle from the leftover portion of bear meat revealed that the bear was infected with Trichinella murrelli, a sylvatic species of Trichinella found in temperate North America. Clinical records revealed a high attack rate for this outbreak: 78% for persons consuming any bear meat and 100% for persons consuming raw or undercooked bear meat. To our knowledge, this report is the first published report of a human trichinellosis outbreak in the United States attributed to T. murrelli, and it is the second such outbreak reported worldwide. |
A hybrid approach for the automated finishing of bacterial genomes.
Bashir A , Klammer AA , Robins WP , Chin CS , Webster D , Paxinos E , Hsu D , Ashby M , Wang S , Peluso P , Sebra R , Sorenson J , Bullard J , Yen J , Valdovino M , Mollova E , Luong K , Lin S , Lamay B , Joshi A , Rowe L , Frace M , Tarr CL , Turnsek M , Davis BM , Kasarskis A , Mekalanos JJ , Waldor MK , Schadt EE . Nat Biotechnol 2012 30 (7) 701-707 Advances in DNA sequencing technology have improved our ability to characterize most genomic diversity. However, accurate resolution of large structural events is challenging because of the short read lengths of second-generation technologies. Third-generation sequencing technologies, which can yield longer multikilobase reads, have the potential to address limitations associated with genome assembly. Here we combine sequencing data from second- and third-generation DNA sequencing technologies to assemble the two-chromosome genome of a recent Haitian cholera outbreak strain into two nearly finished contigs at >99.9% accuracy. Complex regions with clinically relevant structure were completely resolved. In separate control assemblies on experimental and simulated data for the canonical N16961 cholera reference strain, we obtained 14 scaffolds of greater than 1 kb for the experimental data and 8 scaffolds of greater than 1 kb for the simulated data, which allowed us to correct several errors in contigs assembled from the short-read data alone. This work provides a blueprint for the next generation of rapid microbial identification and full-genome assembly. |
Reverse genetics recovery of Lujo virus and role of virus RNA secondary structures in efficient virus growth.
Bergeron E , Chakrabarti AK , Bird BH , Dodd KA , McMullan LK , Spiropoulou CF , Nichol ST , Albarino CG . J Virol 2012 86 (19) 10759-65 Arenaviruses are rodent-borne viruses with a bisegmented RNA genome. A genetically unique arenavirus, Lujo virus, was recently discovered as the causal agent of a nosocomial outbreak of acute febrile illness with hemorrhagic manifestations in Zambia and South Africa. The outbreak had a case fatality of 80%. A reverse genetics system to rescue infectious Lujo virus from cDNA was established to investigate the biological properties of this virus. Sequencing the genomic termini showed unique nucleotides at the 3' terminus of the S segment promoter element. While developing this system, we discovered that reconstructing infectious Lujo virus using the previously reported L segment intergenic region (IGR), comprising the arenaviral transcription termination signal, yielded an attenuated Lujo virus. Resequencing revealed that the correct L segment IGR was 36 nucleotide longer, and incorporating it into the reconstructed Lujo virus restored growth rate to that of the authentic clinical virus isolate. These additional nucleotides were predicted to more than double the free energy of the IGR main stem-loop structure. In addition, incorporating the newly determined L-IGR into a replicon reporter system enhanced the expression of a luciferase reporter L segment. Overall, these results imply that an extremely stable secondary structure within the L-IGR is critical for Lujo virus propagation and viral protein production. The technology for producing recombinant Lujo virus now provides a method to precisely investigate the molecular determinants of virulence of this newly identified pathogen. |
Ethnicity interacts with the OPRM1 gene in experimental pain sensitivity
Hastie BA , Riley JL 3rd , Kaplan L , Herrera DG , Campbell CM , Virtusio K , Mogil JS , Wallace MR , Fillingim RB . Pain 2012 153 (8) 1610-9 Robust interindividual variation in pain sensitivity has been observed, and recent evidence suggests that some of the variability may be genetically mediated. Our previous data revealed significantly higher pressure pain thresholds among individuals possessing the minor G allele of the A118G SNP of the mu-opioid receptor gene (OPRM1) compared with those with 2 consensus alleles. Moreover, ethnic differences in pain sensitivity have been widely reported. Yet, little is known about the potential interactive associations of ethnicity and genotype with pain perception. This study aimed to identify ethnic differences in OPRM1 allelic associations with experimental pain responses. A total of 247 healthy young adults from three ethnic groups (81 African Americans; 79 non-white Hispanics; and 87 non-Hispanic whites) underwent multiple experimental pain modalities (thermal, pressure, ischemic, cold pressor). Few African Americans (7.4%) expressed the rare allele of OPRM1 compared to non-Hispanic whites and Hispanics (28.7% vs. 27.8%, respectively). Across the entire sample, OPRM1 genotype did not significantly affect pain sensitivity. However, analysis in each ethnic group separately revealed significant genotype effects for most pain modalities among non-Hispanic-whites (P<.05) but not Hispanics or African Americans. The G allele was associated with decreased pain sensitivity among whites only; a trend in the opposite direction emerged in Hispanics. The reasons for this dichotomy are unclear; they may involve ethnic differences in haplotypic structure, or A118G may be a tag-SNP linked to other functional polymorphisms. These findings demonstrate an ethnicity-dependent association of OPRM1 genotype with pain sensitivity. Additional research is warranted to uncover the mechanisms influencing these relationships. |
Solid organ transplant-associated lymphocytic choriomeningitis, United States, 2011
MacNeil A , Stroher U , Farnon E , Campbell S , Cannon D , Paddock CD , Drew CP , Kuehnert M , Knust B , Gruenenfelder R , Zaki SR , Rollin PE , Nichol ST . Emerg Infect Dis 2012 18 (8) 1256-1262 Three clusters of organ transplant-associated lymphocytic choriomeningitis virus (LCMV) transmissions have been identified in the United States; 9 of 10 recipients died. In February 2011, we identified a fourth cluster of organ transplant-associated LCMV infections. Diabetic ketoacidosis developed in the organ donor in December 2010; she died with generalized brain edema after a short hospitalization. Both kidneys, liver, and lung were transplanted to 4 recipients; in all 4, severe posttransplant illness developed; 2 recipients died. Through multiple diagnostic methods, we identified LCMV infection in all persons, including in at least 1 sample from the donor and 4 recipients by reverse transcription PCR, and sequences of a 396-bp fragment of the large segment of the virus from all 5 persons were identical. In this cluster, all recipients developed severe illness, but 2 survived. LCMV infection should be considered as a possible cause of severe posttransplant illness. |
A varicella outbreak in a school with high one-dose vaccination coverage, Beijing, China
Lu L , Suo L , Li J , Zhai L , Zheng Q , Pang X , Bialek SR , Wang C . Vaccine 2012 30 (34) 5094-8 BACKGROUND: Varicella vaccine is available in the private sector in China, with a single dose currently recommended for children aged ≥12 months. We investigated a varicella outbreak in a school in Beijing with high varicella vaccination coverage to describe the outbreak, examine risk factors for vaccine failure, and calculate vaccine effectiveness. METHODS: A varicella case was defined as an acute generalized maculopapular rash without other apparent cause in a student without prior varicella attending the elementary school during August 30-December 28, 2010. Varicella among vaccinated students (breakthrough varicella) was defined as varicella occurring >42 days after vaccination. Students' vaccination status was verified with immunization records and clinical presentations were collected from health care practitioners. RESULTS: Of the 951 students, 934 (98%) had no prior varicella history. Among these students, 916 had received 1 dose of varicella vaccine and 2 had received 2 doses (98% vaccination coverage) before the outbreak. A total of 87 cases occurred during the outbreak; most had breakthrough varicella (86/87, 99%) and mild disease (83/87, 95%). Age at vaccination (<15 months vs. ≥15 months) and time since vaccination before outbreak (<5 years vs. ≥5 years) were not associated with development of breakthrough varicella. Single-dose varicella vaccination was 89% effective in preventing any varicella and 99% in preventing moderate/severe varicella. CONCLUSION: Single-dose varicella vaccination is highly effective in reducing varicella incidence and mitigating disease severity, but not high enough to prevent outbreak. A two-dose program might help to prevent varicella outbreaks in Beijing. |
Antibody persistence in mothers one year after pneumococcal immunization in pregnancy
Schlaudecker EP , Steinhoff MC , Omer SB , Roy E , Arifeen SE , Dodd CN , Altaye M , Raqib R , Breiman RF , Zaman K . Vaccine 2012 30 (34) 5063-6 BACKGROUND: Pneumococcal infections are a significant cause of morbidity and mortality, and young infants are particularly vulnerable to infection. Maternal immunization can protect infants, but there are limited data on the duration of pneumococcal vaccine antibody in pregnant women. We report on maternal antibody concentrations one year after immunization with 23-valent pneumococcal polysaccharide (23vPPS) vaccine. METHOD: The Mother's Gift study randomly assigned 340 pregnant Bangladeshi mothers between ages 18 and 36 to receive either inactivated influenza vaccine (Fluarix((R))) or the 23vPPS vaccine (Pneumovax((R))) during the third trimester. Sera were collected before immunization, at delivery, and at one year post-delivery. We determined anti-capsular IgG antibody to 9 pneumococcal serotypes by a multiplex Luminex ELISA. We report antibody geometric mean concentrations (GMCs) for 9 serotypes, 12 month/delivery geometric mean ratios (GMRs) and proportions seroprotected (>0.35mcg/mL) in 23vPPS vaccine recipients and controls at delivery and at 12 months. RESULTS: Among pneumococcal vaccinees, GMCs remained stable, with an overall 12 month/delivery GMR of 0.83 (95% CI, 0.75-0.92). In the control group, GMCs increased with a mean ratio of 1.98 (95% CI, 1.81-2.17; P<0.0001). GMCs in these vaccinees did not decline significantly in the 12 months after antenatal immunization. CONCLUSION: GMCs in these adult vaccinees and controls did not decline significantly in the 12 months after antenatal immunization. Interestingly, mothers who did not receive 23vPPS in pregnancy show a substantial increase of GMC for most serotypes in the first year after immunization. Further studies are needed to determine the need for repeat doses of 23vPPS vaccine in subsequent pregnancies more than a year later. |
Rapid differentiation of monocytes into type I IFN-producing myeloid dendritic cells as an antiviral strategy against influenza virus infection
Cao W , Taylor AK , Biber RE , Davis WG , Kim JH , Reber AJ , Chirkova T , De La Cruz JA , Pandey A , Ranjan P , Katz JM , Gangappa S , Sambhara S . J Immunol 2012 189 (5) 2257-65 Myeloid dendritic cells (mDCs) have long been thought to function as classical APCs for T cell responses. However, we demonstrate that influenza viruses induce rapid differentiation of human monocytes into mDCs. Unlike the classic mDCs, the virus-induced mDCs failed to upregulate DC maturation markers and were unable to induce allogeneic lymphoproliferation. Virus-induced mDCs secreted little, if any, proinflammatory cytokines; however, they secreted a substantial amount of chemoattractants for monocytes (MCP-1 and IP-10). Interestingly, the differentiated mDCs secreted type I IFN and upregulated the expression of IFN-stimulated genes (tetherin, IFITM3, and viperin), as well as cytosolic viral RNA sensors (RIG-I and MDA5). Additionally, culture supernatants from virus-induced mDCs suppressed the replication of virus in vitro. Furthermore, depletion of monocytes in a mouse model of influenza infection caused significant reduction of lung mDC numbers, as well as type I IFN production in the lung. Consequently, increased lung virus titer and higher mortality were observed. Taken together, our results demonstrate that the host responds to influenza virus infection by initiating rapid differentiation of circulating monocytes into IFN-producing mDCs, which contribute to innate antiviral immune responses. |
TLR7 recognition is dispensable for influenza virus A infection, but important for the induction of hemagglutinin-specific antibodies in response to the 2009 pandemic split vaccine in mice
Jeisy-Scott V , Kim JH , Davis WG , Cao W , Katz JM , Sambhara S . J Virol 2012 86 (20) 10988-98 Recognition of pathogen associated molecular patterns by pattern recognition receptors of the innate immune system is crucial for the initiation of innate and adaptive responses and for immunological memory. We investigated the role of TLR7 in the induction of adaptive immunity and long-term memory following influenza virus infection and vaccination in C57Bl/6 mice. During infection with influenza A/PR8/34 virus, the absence of either TLR7 or MyD88 leads to reduced serum IgM and fewer IgM secreting B-cells in their secondary lymphoid organs, particularly in bone marrow. In spite of this, the absence of TLR7/MyD88 signaling did not impair the production of protective antibodies. Following immunization with the 2009 pandemic inactivated split vaccine, TLR7(-/-) mice had significantly lower levels of germinal center formation, antibody secreting cells and circulating influenza-specific antibodies than control animals. Consequently, TLR7(-/-) mice failed to develop protective immunological memory upon challenge. Furthermore, the immunogenicity of the split vaccine was likely due to TLR7 recognition of virion RNA, as its removal from the split vaccine significantly reduced the levels of influenza-specific antibodies, and compromised the vaccine protective efficacy in mice. Taken together, our data demonstrate that TLR7 plays an important role in vaccine-induced humoral immune responses to influenza through the interaction with viral RNA present in the split vaccine. |
Population diversity among Bordetella pertussis isolates, United States, 1935-2009
Schmidtke AJ , Boney KO , Martin SW , Skoff TH , Tondella ML , Tatti KM . Emerg Infect Dis 2012 18 (8) 1248-55 Since the 1980s, pertussis notifications in the United States have been increasing. To determine the types of Bordetella pertussis responsible for these increases, we divided 661 B. pertussis isolates collected in the United States during 1935-2009 into 8 periods related to the introduction of novel vaccines or changes in vaccination schedule. B. pertussis diversity was highest from 1970-1990 (94%) but declined to approximately 70% after 1991 and has remained constant. During 2006-2009, 81.6% of the strains encoded multilocus sequence type prn2-ptxP3-ptxS1A-fim3B, and 64% were multilocus variable number tandem repeat analysis type 27. US trends were consistent with those seen internationally; emergence and predominance of the fim3B allele was the only molecular characteristic associated with the increase in pertussis notifications. Changes in the vaccine composition and schedule were not the direct selection pressures that resulted in the allele changes present in the current B. pertussis population. |
Prediction of acute mammalian toxicity using QSAR methods: a case study of sulfur mustard and its breakdown products
Ruiz P , Begluitti G , Tincher T , Wheeler J , Mumtaz M . Molecules 2012 17 (8) 8982-9001 Predicting toxicity quantitatively, using Quantitative Structure Activity Relationships (QSAR), has matured over recent years to the point that the predictions can be used to help identify missing comparison values in a substance's database. In this manuscript we investigate using the lethal dose that kills fifty percent of a test population (the LD50) for determining relative toxicity of a number of substances. In general, the smaller the LD50 value, the more toxic the chemical, and the larger the LD50 value, the lower the toxicity. When systemic toxicity and other specific toxicity data are unavailable for the chemical(s) of interest, during emergency responses, LD50 values may be employed to determine the relative toxicity of a series of chemicals. In the present study, a group of chemical warfare agents and their breakdown products have been evaluated using four available rat oral QSAR LD50 models. The QSAR analysis shows that the breakdown products of Sulfur Mustard (HD) are predicted to be less toxic than the parent compound as well as other known breakdown products that have known toxicities. The QSAR estimated break down products LD50 values ranged from 299 mg/kg to 5,764 mg/kg. This evaluation allows for the ranking and toxicity estimation of compounds for which little toxicity information existed; thus leading to better risk decision making in the field. |
Preliminary studies on the use of acid-soluble cellulose acetate internal capsules for workplace metals sampling and analysis
Harper M , Ashley K . J Occup Environ Hyg 2012 9 (7) D125-D129 Particles entering filter cassettes used to collect samples of aerosol can deposit elsewhere than on the filter. One suggested procedure for ensuring that those deposits are included in the analysis is to collect them within an internal capsule that can subsequently be digested along with the filter. An inter-laboratory evaluation was carried out to evaluate the use of cellulosic capsule inserts for their suitability in the determination of trace elements in workplace air samples. The inter-laboratory study (ILS) was performed in accordance with an applicable ASTM International standard practice, ASTM E691, which describes statistical procedures for investigating inter-laboratory precision. Performance evaluation materials consisted of prototype cellulose acetate capsules attached to mixed-cellulose ester filters, which were spiked with lead-containing materials (aqueous salt solutions, certified reference soil and paint) at ≈ 20 and ≈ 50 µg Pb per sample. Triplicates of each spiked capsule plus media blanks were conveyed to each volunteer laboratory; spiking levels were unknown to the participants. The laboratories were asked to prepare the samples by acid digestion and analyze aliquots of extracted samples by atomic spectrometry procedures described in applicable ASTM International standard test methods D7035 and/or D7439. Participants were then asked to report their data in units of µg per sample. Preliminary inter-laboratory precision and recovery estimates from six participating laboratories demonstrated the utility of the cellulosic capsule inserts for the measurement of sampled trace elements. |
Probability of negative Mycobacterium tuberculosis complex cultures based on time-to-detection of positive cultures: a multi-center evaluation of commercial broth-based culture systems
Tyrrell FC , Budnick GE , Elliott T , Gillim-Ross L , Hildred MV , Mahlmeister P , Parrish N , Pentella M , Vanneste J , Wang YF , Starks AM . J Clin Microbiol 2012 50 (10) 3275-82 We conducted a multicenter study to determine whether Mycobacterium tuberculosis complex (MTBC) cultures in automated broth-based systems could reliably be considered as negative sooner than six weeks. Laboratory sites used MGIT or BacT/ALERT and tracked results of time to detection of mycobacteria (TTD-all, n = 1547) and MTBC (TTD-MTBC, n = 466) over six-month periods from primarily (93%) respiratory specimens. Cumulative percentages by day detected and median TTD of initial and follow-up specimens were analyzed. The median TTD-MTBC for MGIT (n = 6 sites) was 14 days. For laboratories using standard processing procedures, 100% of MTBC were detected from initial and follow-up specimens in 28 and 35 days, respectively, and no yield of MTBC on solid or MGIT liquid media was observed after five weeks. The median TTD-MTBC for BacT/ALERT (n = 3 sites) was 18 days, with 95% and 100% detected within 37 and 42 days respectively. Analysis of TTD of positive MTBC cultures in broth can predict the probability of culture negativity at defined time points. Receipt of interim negative reports earlier than six weeks could assist clinicians in considering alternative diagnoses, and could alter timing and prioritization of public health interventions. Laboratories should analyze their own TTD data to inform protocol decisions. Laboratories using MGIT could issue no growth of MTBC reports on initial specimens as early as four weeks and on patients undergoing treatment as early as five weeks post-inoculation. |
Chemical and biochemical approaches in the study of histone methylation and demethylation
Li KK , Luo C , Wang D , Jiang H , Zheng YG . Med Res Rev 2012 32 (4) 815-67 Histone methylation represents one of the most critical epigenetic events in DNA function regulation in eukaryotic organisms. Classic molecular biology and genetics tools provide significant knowledge about mechanisms and physiological roles of histone methyltransferases and demethylases in various cellular processes. In addition to this stream line, development and application of chemistry and chemistry-related techniques are increasingly involved in biological study, and offer information otherwise difficult to obtain by standard molecular biology methods. Herein, we review recent achievements and progress in developing and applying chemical and biochemical approaches in the study of histone methylation, including chromatin immunoprecipitation, chemical ligation, mass spectrometry, biochemical methylation and demethylation assays, and inhibitor development. These technological advances allow histone methylation to be studied from genome-wide level to molecular and atomic levels. With ChIP technology, information can be obtained about precise mapping of histone methylation patterns at specific promoters, genes, or other genomic regions. MS is particularly useful in detecting and analyzing methylation marks in histone and nonhistone protein substrates. Chemical approaches that permit site-specific incorporation of methyl groups into histone proteins greatly facilitate the investigation of biological impacts of methylation at individual modification sites. Discovery and design of selective organic inhibitors of histone methyltransferases and demethylases provide chemical probes to interrogate methylation-mediated cellular pathways. Overall, these chemistry-related technological advances have greatly improved our understanding of the biological functions of histone methylation in normal physiology and diseased states, and also are of great potential to translate basic epigenetics research into diagnostic and therapeutic applications in the clinic. ((c) 2010 Wiley Periodicals, Inc. Med Res Rev., 32, No. 4, 815-867, 2012.) |
Health care utilization in the first year of life among small- and large- for-gestational age term infants
Dietz PM , Rizzo JH , England LJ , Callaghan WM , Vesco KK , Bruce FC , Bulkley JE , Sharma AJ , Hornbrook MC . Matern Child Health J 2012 17 (6) 1016-24 The objective of the study was to assess if small- and large-for gestational age term infants have greater health care utilization during the first year of life. The sample included 28,215 singleton term infants (37-42 weeks) without major birth defects delivered from 1998 through 2007 and continuously enrolled at Kaiser Permanente Northwest for 12 months after delivery. Birth weight for gestational age was categorized into 3 levels: <10th percentile (SGA), 10-90th percentile (AGA), >90th percentile (LGA). Length of delivery hospitalization, re-hospitalizations and sick/emergency room visits were obtained from electronic records. Logistic regression models estimated associations between birth weight category and re-hospitalization. Generalized linear models estimated adjusted mean number of sick/emergency visits. Among term infants, 6.2 % were SGA and 13.9 % were LGA. Of infants born by cesarean section, SGA infants had 2.7 higher odds [95 % 1.9, 3.8] than AGA infants of staying ≥5 nights during the delivery hospitalization; of those born vaginally, SGA infants had 1.5 higher adjusted odds [95 % 1.1, 2.1] of staying ≥4 nights. LGA compared to AGA infants had higher odds of re-hospitalization within 2 weeks of delivery [OR 1.25, 95 % CI 0.99, 1.58] and of a length of stay ≥4 days during that hospitalization [OR 2.6, 95 % CI 1.3, 5.0]. The adjusted mean number of sick/emergency room visits was slightly higher in SGA (7.8) than AGA (7.5) infants (P < .05). Term infants born SGA or LGA had greater health care utilization than their counterparts, although the increase in utilization beyond the initial delivery hospitalization was small. |
Sodium and potassium intakes among US adults: NHANES 2003-2008
Cogswell ME , Zhang Z , Carriquiry AL , Gunn JP , Kuklina EV , Saydah SH , Yang Q , Moshfegh AJ . Am J Clin Nutr 2012 96 (3) 647-57 BACKGROUND: The American Heart Association (AHA), Institute of Medicine (IOM), and US Departments of Health and Human Services and Agriculture (USDA) Dietary Guidelines for Americans all recommend that Americans limit sodium intake and choose foods that contain potassium to decrease the risk of hypertension and other adverse health outcomes. OBJECTIVE: We estimated the distributions of usual daily sodium and potassium intakes by sociodemographic and health characteristics relative to current recommendations. DESIGN: We used 24-h dietary recalls and other data from 12,581 adults aged ≥20 y who participated in NHANES in 2003-2008. Estimates of sodium and potassium intakes were adjusted for within-individual day-to-day variation by using measurement error models. SEs and 95% CIs were assessed by using jackknife replicate weights. RESULTS: Overall, 99.4% (95% CI: 99.3%, 99.5%) of US adults consumed more sodium daily than recommended by the AHA (<1500 mg), and 90.7% (89.6%, 91.8%) consumed more than the IOM Tolerable Upper Intake Level (2300 mg). In US adults, who are recommended by the Dietary Guidelines to further reduce sodium intake to 1500 mg/d (ie, African Americans aged ≥51 y or persons with hypertension, diabetes, or chronic kidney disease), 98.8% (98.4%, 99.2%) overall consumed >1500 mg/d and 60.4% consumed >3000 mg/d-more than double the recommendation. Overall, <2% of US adults and approximately 5% of US men consumed ≥4700 mg K/d (ie, met recommendations for potassium). CONCLUSION: Regardless of recommendations or sociodemographic or health characteristics, the vast majority of US adults consume too much sodium and too little potassium. |
A multistate examination of partnership activity among local public health systems using the National Public Health Performance Standards
Barnes PA , Curtis AB , Hall-Downey L , Moonesinghe R . J Public Health Manag Pract 2012 18 (5) E14-23 This study examines whether partnership-related measures in the second version of the National Public Health Performance Standards (NPHPS) are useful in evaluating level of activity as well as identifying latent constructs that exist among local public health systems (LPHSs). In a sample of 110 LPHSs, descriptive analysis was conducted to determine frequency and percentage of 18 partnership-related NPHPS measures. Principal components factor analysis was conducted to identify unobserved characteristics that promote effective partnerships among LPHSs. Results revealed that 13 of the 18 measures were most frequently reported at the minimal-moderate level (conducted 1%-49% of the time). Coordination of personal health and social services to optimize access (74.6%) was the most frequently reported measure at minimal-moderate levels. Optimal levels (conducted >75% of the time) were reported most frequently in 2 activities: participation in emergency preparedness coalitions and local health departments ensuring service provision by working with state health departments (67% and 61% of respondents, respectively) and the least optimally reported activity was review partnership effectiveness (4% of respondents). Factor analysis revealed categories of partnership-related measures in 4 domains: resources and activities contributing to relationship building, evaluating community leadership activities, research, and state and local linkages to support public health activities. System-oriented public health assessments may have questions that serve as proxy measures to examine levels of interorganizational partnerships. Several measures from the NPHPS were useful in establishing a national baseline of minimal and optimal activity levels as well as identifying factors to enhance the delivery of the 10 essential public health services among organizations and individuals in public health systems. |
Functions of environmental epidemiology and surveillance in state health departments
Stanbury M , Anderson H , Blackmore C , Fagliano J , Heumann M , Kass D , McGeehin M . J Public Health Manag Pract 2012 18 (5) 453-460 Public health surveillance and epidemiology are the foundations for disease prevention because they provide the factual basis from which agencies can set priorities, plan programs, and take actions to protect the public's health. Surveillance for noninfectious diseases associated with exposure to agents in the environment like lead and pesticides has been a function of state health departments for more than 3 decades, but many state programs do not have adequate funding or staff for this function. Following the efforts to identify core public health epidemiology functions in chronic diseases, injury, and occupational health and safety, a workgroup of public health environmental epidemiologists operating within the organizational structure of the Council of State and Territorial Epidemiologists has defined the essential core functions of noninfectious disease environmental epidemiology that should be present in every state health department and additional functions of a comprehensive program. These functions are described in terms of the "10 Essential Environmental Public Health Services" and their associated performance standards. Application of these consensus core and expanded functions should help state and large metropolitan health departments allocate resources and prioritize activities of their environmental epidemiologists, thus improving the delivery of environmental health services to the public. |
A hierarchical Bayesian nonresponse model for two-way categorical data from small areas with uncertainty about ignorability
Nandram B , Katzoff M . Surv Methodol 2012 38 (1) 81-93 We study the problem of nonignorable nonresponse in a two dimensional contingency table which can be constructed for each of several small areas when there is both item and unit nonresponse. In general, the provision for both types of nonresponse with small areas introduces significant additional complexity in the estimation of model parameters. For this paper, we conceptualize the full data array for each area to consist of a table for complete data and three supplemental tables for missing row data, missing column data, and missing row and column data. For nonignorable nonresponse, the total cell probabilities are allowed to vary by area, cell and these three types of "missingness". The underlying cell probabilities (i.e., those which would apply if full classification were always possible) for each area are generated from a common distribution and their similarity across the areas is parametrically quantified. Our approach is an extension of the selection approach for nonignorable nonresponse investigated by Nandram and Choi (2002a, b) for binary data; this extension creates additional complexity because of the multivariate nature of the data coupled with the small area structure. As in that earlier work, the extension is an expansion model centered on an ignorable nonresponse model so that the total cell probability is dependent upon which of the categories is the response. Our investigation employs hierarchical Bayesian models and Markov chain Monte Carlo methods for posterior inference. The models and methods are illustrated with data from the third National Health and Nutrition Examination Survey. |
Content Index (Achived Edition)
- Chronic Diseases and Conditions
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- Epidemiology and Surveillance
- Food Safety
- Genetics and Genomics
- Healthcare Associated Infections
- Immunity and Immunization
- Laboratory Sciences
- Maternal and Child Health
- Nutritional Sciences
- Public Health Leadership and Management
- Statistics as Topic
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