The Mississippi Delta Cardiovascular Health Examination Survey: study design and methods
Short VL , Ivory-Walls T , Smith L , Loustalot F . Epidemiol Res Int 2014 2014 (861461) 861461 Assessment of cardiovascular disease (CVD) morbidity and mortality in subnational areas is limited. A model for regional CVD surveillance is needed, particularly among vulnerable populations underrepresented in current monitoring systems. The Mississippi Delta Cardiovascular Health Examination Survey (CHES) is a population-based, cross-sectional study on a representative sample of adults living in the 18-county Mississippi Delta region, a rural, impoverished area with high rates of poor health outcomes and marked health disparities. The primary objectives of Delta CHES are to (1) determine the prevalence and distribution of CVD and CVD risk factors using self-reported and directly measured health metrics and (2) to assess environmental perceptions and existing policies that support or deter healthy choices. An address-based sampling frame is used for household enumeration and participant recruitment and an in-home data collection model is used to collect survey data, anthropometric measures, and blood samples from participants. Data from all sources will be merged into one analytic dataset and sample weights developed to ensure data are representative of the Mississippi Delta region adult population. Information gathered will be used to assess the burden of CVD and guide the development, implementation, and evaluation of cardiovascular health promotion and risk factor control strategies. |
Mutations within the rplD Gene of Linezolid-Nonsusceptible Streptococcus pneumoniae Strains Isolated in the United States.
Dong W , Chochua S , McGee L , Jackson D , Klugman KP , Vidal JE . Antimicrob Agents Chemother 2014 58 (4) 2459-62 Three invasive Streptococcus pneumoniae strains nonsusceptible to linezolid were isolated in the United States between 2001 and 2012 from the CDC's Active Bacterial Core surveillance. Linezolid binds ribosomal proteins where structural changes within its target site may confer resistance. Our study identified mutations and deletions near the linezolid binding pocket of two of these strains within the rplD gene, which encodes ribosomal protein L4. Mutations in the 23S rRNA alleles or the rplV gene were not detected. |
Risk for HIV following a diagnosis of syphilis, gonorrhoea or chlamydia: 328,456 women in Florida, 2000-2011
Peterman TA , Newman DR , Maddox L , Schmitt K , Shiver S . Int J STD AIDS 2014 26 (2) 113-9 BACKGROUND: Several effective interventions are available for preventing HIV in women. Targeting interventions requires understanding their risk of acquiring HIV. METHODS: We used surveillance data to estimate risks of HIV acquisition for 13-59-year-old women following a diagnosis of syphilis, gonorrhoea or chlamydia in Florida during 2000-2009. We excluded women reported with HIV before their STI, and measured HIV reported subsequent to STI (through 2011). Rates were compared to women with no reported STI. RESULTS: A total of 328,456 women had: syphilis (3325), gonorrhoea (67,784) or chlamydia (257,347). During 2,221,944 person-years of follow-up, 2118 of them were diagnosed with HIV. For women with no STI reported, during 64,763,832 person-years, 19,531 were reported with HIV. The crude rate of subsequent HIV diagnosis (per 100,000 person-years) was higher for women diagnosed with syphilis (597.9), gonorrhoea (171.3) or chlamydia (66.3) than women with no STI (30.2). Annual rates of HIV decreased over-all by 61.8% between 2001 and 2011. CONCLUSION: Women with syphilis or gonorrhoea were at highest risk for HIV and therefore might benefit from intensive counselling. However, they represented only a small fraction of the women who acquired HIV. Most cases of HIV infection among women occurred among the large group of women who were not at highest risk. |
A systematic review of interventions for reducing HIV risk behaviors among people living with HIV in the United States, 1988-2012
Crepaz N , Tungol-Ashmon MV , Higa DH , Vosburgh W , Mullins MM , Barham T , Adegbite A , DeLuca JB , Sipe TA , White CM , Baack BN , Lyles CM . AIDS 2014 28 (5) 633-656 OBJECTIVE: To conduct a systematic review to examine interventions for reducing HIV risk behaviors among people living with HIV (PLWH) in the United States. METHODS: Systematic searches included electronic databases from 1988 to 2012, hand searches of journals, reference lists of articles, and HIV/AIDS Internet listservs. Each eligible study was evaluated against the established criteria on study design, implementation, analysis, and strength of findings to assess the risk of bias and intervention effects. RESULTS: Forty-eight studies were evaluated. Fourteen studies (29%) with both low risk of bias and significant positive intervention effects in reducing HIV transmission risk behaviors were classified as evidence-based interventions (EBIs). Thirty-four studies were classified as non-EBIs due to high risk of bias or nonsignificant positive intervention effects. EBIs varied in delivery from brief prevention messages to intensive multisession interventions. The key components of EBIs included addressing HIV risk reduction behaviors, motivation for behavioral change, misconception about HIV, and issues related to mental health, medication adherence, and HIV transmission risk behavior. CONCLUSION: Moving evidence-based prevention for PLWH into practice is an important step in making a greater impact on the HIV epidemic. Efficacious EBIs can serve as model programs for providers in healthcare and nonhealthcare settings looking to implement evidence-based HIV prevention. Clinics and public health agencies at the state, local, and federal levels can use the results of this review as a resource when making decisions that meet the needs of PLWH to achieve the greatest impact on the HIV epidemic. |
Unplanned pregnancies among HIV-infected women in care - United States
Sutton MY , Patel R , Frazier EL . J Acquir Immune Defic Syndr 2014 65 (3) 350-8 OBJECTIVE: To examine the prevalence of unplanned pregnancies among HIV-infected women in care in the United States. METHODS: We used the 2007-2008 cycles of the Medical Monitoring Project, which collected data on HIV-infected adults in care. Women were included if they had an HIV diagnosis before 45 years of age and responded to questions about pregnancies and pregnancy planning after HIV diagnosis. Logistic regression was used to calculate unadjusted and adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for correlates of unplanned pregnancies among women with ≥ 1 pregnancy at or after an HIV diagnosis. RESULTS: Of 1492 women, 382 (25.6%) reported ≥ 1 pregnancy after HIV diagnosis (median diagnosis age = 25.0 years; interquartile range = 21.0-30.0); 58% were non-Hispanic black, 22% Hispanic, and 15% non-Hispanic white. Of those, 326 (85.3%) reported ≥ 1 unplanned pregnancy; 124 (32.5%) reported recent unprotected vaginal and/or anal sex with a male partner with either negative or unknown HIV status. Unplanned pregnancies were more likely among women who reported nadir CD4 cell counts <200 cells/muL (AOR = 2.3; 95% CI: 1.2 to 4.8) or did not report nadir CD4 cell counts (AOR = 4.3; 95% CI: 1.9 to 10.5) compared with women who reported nadir CD4 cell counts ≥ 200 cells/muL; and who received public assistance in the most recent year before Medical Monitoring Project interview (AOR = 2.1; 95% CI: 1.1 to 3.8) compared with women who did not receive assistance. CONCLUSIONS: Unplanned pregnancies were prevalent among our sample. To avoid unplanned pregnancies, HIV-infected women need access to effective family planning services and risk reduction discussions during routine care visits. |
Using tuberculosis patient characteristics to predict future cases with matching genotype results
Oeltmann JE , Click ES , Moonan PK . Public Health Action 2014 4 (1) 47-52 BACKGROUND: It is unknown whether tuberculosis (TB) case or patient characteristics can predict the likelihood of future related TB cases. OBJECTIVE: To estimate the likelihood for future related cases, i.e., cases with matching TB genotypes within the same county diagnosed within the 2 years following the year of reporting of each included case. DESIGN: We considered all TB cases with genotyping results reported in the United States during 2004-2010. Predictive scores were calculated based on patient characteristics by dividing the number of patients who were not the last case in a county-level TB genotype cluster by the total number of patients. RESULTS: Overall, there was a 30.8% chance that a future related case would be detected during the 2 years following the report year of any given case. Future related cases were detected in 34.7% of instances following the diagnosis of smear-positive cases, 51.9% of instances following the diagnosis of a homeless patient and 45.2% of instances following the diagnosis of a patient who reported substance abuse. Predictive scores ranged by race (White 13.9%, Native Hawaiian 43.8%) and age group (>65 years 13.1%, 0-4 years 43%), and were higher for US-born patients. CONCLUSIONS: Behavioral and sociodemographic factors can help predict the likelihood of future related cases and can be used to prioritize contact investigations. |
Varicella zoster virus in American Samoa: seroprevalence and predictive value of varicella disease history in elementary and college students
Mahamud A , Leung J , Masunu-Faleafaga Y , Teshale E , Williams R , Dulski T , Thieme M , Garcia P , Schmid DS , Bialek SR . Epidemiol Infect 2014 142 (5) 1002-7 The epidemiology of varicella is believed to differ between temperate and tropical countries. We conducted a varicella seroprevalence study in elementary and college students in the US territory of American Samoa before introduction of a routine varicella vaccination programme. Sera from 515 elementary and 208 college students were tested for the presence of varicella-zoster virus (VZV) IgG antibodies. VZV seroprevalence increased with age from 76.0% in the 4-6 years group to 97.7% in those aged 23 years. Reported history of varicella disease for elementary students was significantly associated with VZV seropositivity. The positive and negative predictive values of varicella disease history were 93.4% and 36.4%, respectively, in elementary students and 97.6% and 3.0%, respectively, in college students. VZV seroprevalence in this Pacific island appears to be similar to that in temperate countries and suggests endemic VZV circulation. |
Measles outbreak associated with adopted children from China - Missouri, Minnesota, and Washington, July 2013
Nyangoma EN , Olson CK , Benoit SR , Bos J , Debolt C , Kay M , Rietberg K , Tasslimi A , Baker D , Feng X , Lippold S , Blumensaadt S , Schembri C , Vang A , Burke H , Wallace G , Zhou W . MMWR Morb Mortal Wkly Rep 2014 63 (14) 301-4 On July 5, 2013, CDC was notified of two cases of laboratory-confirmed measles in recently adopted children from an orphanage in Henan Province, China. To find potentially exposed persons, CDC collaborated with state and local health departments, the children's adoption agency, and airlines that carried the adoptees. Two additional measles cases were identified, one in a family member of an adoptee and one in a third adopted child from China. To prevent further importation of measles, CDC worked with health officials in China, including "panel physicians" contracted by the U.S. Department of State to conduct the overseas medical examinations required for all immigrants and refugees bound for the United States. The following measures were recommended: 1) all adoptees examined at panel physician facilities should be screened for fever and rash illness, 2) measles immunity should be ensured among all adoptees from Henan Province who are scheduled for imminent departure to the United States, and 3) all children at the orphanage in Henan Province should be evaluated for measles. This report summarizes the results of the outbreak investigation and underscores the importance of timely routine vaccination for all international adoptees. |
Optimism and education buffer the effects of syndemic conditions on HIV status among African American men who have sex with men
O'Leary A , Jemmott JB 3rd , Stevens R , Rutledge SE , Icard LD . AIDS Behav 2014 18 (11) 2080-8 The present study sought to replicate effects of the number of syndemic psychosocial health conditions on sexual risk behavior and HIV infection among a sample of high-risk African American men who have sex with men (MSM) and to identify resilience factors that may buffer these effects. We used baseline data from an HIV risk-reduction trial to examine whether a higher number of syndemic conditions was associated with higher rates of self-reported sexual risk behavior and HIV infection. Using logistic regression models, we tested for interactions between number of syndemic conditions and several potential resilience factors to identify buffering effects. Replicating previous studies, we found significant associations between numbers of syndemic conditions and higher rates of sexual risk behavior and HIV infection. Surprisingly, we also replicated a previous finding (Stall et al., Am J Public Health, 93(6):939-942, 2003) that the effects of syndemic burden on HIV status fell off at the highest levels of syndemic conditions. Among a variety of potential resilience factors, two-optimism and education-buffered the syndemic effect on HIV prevalence. This is, to our knowledge, the first paper to identify resilience factors buffering against syndemic effects among MSM. It also constitutes a significant contribution to the literature regarding prevention among black MSM. These results point to the need to identify HIV-positive black MSM and provide effective treatment for them and to develop interventions addressing both syndemic and resilience factors. |
Estimating number of diagnosed persons living with HIV in the United States engaged in unprotected serodiscordant risk behavior with unsuppressed viral load
Holtgrave DR , Hall HI , Des Jarlais DC , Mizuno Y , Purcell DW . J Acquir Immune Defic Syndr 2014 65 (3) e125-8 HIV is transmitted primarily through unprotected risk behavior (ie, parenteral or sexual transmission of HIV) in a serostatus discordant partnership with unsuppressed viral load.1,2 Index persons living with HIV (PLWH) may or may not be aware of their HIV seropositivity. Hence, there are 2 key subpopulations of PLWH in the United States who might potentially transmit HIV: undiagnosed PLWH and diagnosed PLWH with unsuppressed virus engaged in unprotected serostatus discordant risk behavior.1–3 It has recently been estimated that as of 2009, there are roughly 50,125 incident infections per year in the United States (this figure is an average over the years 2006 through 2009) and just over 1.148 million PLWH (thereby reflecting an overall transmission rate of 4.4 transmission per 100 PLWH per year).3 Furthermore, it was estimated that 22,364 transmissions are from the 207,824 undiagnosed PLWH (implying a transmission rate of 10.8) and 27,761 from the 95,994 diagnosed PLWH with unsuppressed virus engaged in unprotected serodiscordant risk behavior (resulting in a transmission rate of 28.9).3 This prior analysis assumed that with suppressed viral load and/or the absence of unprotected serodiscordant risk behavior, extremely low levels would occur with a transmission rate approaching 0.3 | Because these 2 subpopulations of PLWH are critical to the transmission of HIV, continually updating estimates of the size and characteristics of the populations is critical. Here, we refine the estimate of the number of diagnosed PLWH with unsuppressed viral load engaged in unprotected serodiscordant risk behavior and provide further information about the characteristics of this key population. In prior analyses, an assumption was made that the level of such risk behavior was similar among persons engaged in sexual risk behavior and persons who inject drugs (this assumption was made due to the lack of information about such risk behavior among persons who inject drugs).3 Now, however, data are available to inform this assumption thereby allowing for a more detailed analysis. |
Factors associated with uptake of HIV test results in a nationally representative population-based AIDS indicator survey
Mwangi M , Kellogg TA , Dadabhai SS , Bunnell R , Baltazar G , Ngare C , K'Opiyo G , Mburu M , Kim AA . Open AIDS J 2014 8 7-16 Population-based surveys with HIV testing in settings with low testing coverage provide opportunities for participants to learn their HIV status. Survey participants (15-64 years) in a 2007 nationally representative population-based HIV serologic survey in Kenya received a voucher to collect HIV test results at health facilities 6 weeks after blood draw. Logistic regression models were fitted to identify predictors of individual and couple collection of results. Of 15,853 adults consenting to blood draw, 7,222 (46.7%) collected HIV test results (46.5% men, 46.8% women). A third (39.5%) of HIV-infected adults who were unaware of their infection and 48.2% of those who had never been tested learned their HIV status during KAIS. Individual collection of HIV results was associated with older age, with the highest odds among adults aged 60-64 years (adjusted odds ratio [AOR], 1.6, 95% confidence interval [CI] 1.2-2.1); rural residence (AOR 1.8, 95%CI 1.2-2.6); and residence outside Nairobi, with the highest odds in the sparsely populated North Eastern province (AOR 8.0, 95%CI 2.9-21.8). Of 2,685 married/cohabiting couples, 18.5% collected results as a couple. Couples in Eastern province and in the second and middle wealth quintiles were more likely to collect results than those in Nairobi (AOR 3.2, 95%CI 1.1-9.4) and the lowest wealth quintile (second AOR 1.5, 95%CI 1.1-2.3; middle AOR 1.6, 95% CI 1.2-2.3, respectively. Many participants including those living with HIV learned their HIV status in KAIS. Future surveys need to address low uptake of results among youth, urban residents, couples and those with undiagnosed HIV infection. |
Hepatitis B virus (HBV) infection, immunity and susceptibility among nen who have sex with men (MSM), Los Angeles County, USA
Pitasi MA , Bingham TA , Sey EK , Smith AJ , Teshale EH . AIDS Behav 2014 18 Suppl 3 248-55 Men who have sex with men (MSM) bear a disproportionate burden of hepatitis B virus (HBV) infections. We used serologic data from the National HIV Behavioral Surveillance (NHBS) system to determine the prevalence and correlates of HBV infection, immunization, and susceptibility in a sample of Los Angeles County MSM. Approximately 19 % (95 % CI 15-24 %) had serologic evidence of current or past infection, while 35 % (95 % CI 30-40 %) were susceptible. Compared with the youngest age group, MSM ages 40-49 years had a lower prevalence of immunization (aPR 0.28, 95 % CI 0.17-0.45) and a higher prevalence of infection (aPR 8.53, 95 % CI 3.95-18.4) and susceptibility (aPR 2.02, 95 % CI 1.13-3.63). We also observed poor concordance between self-reported and serologic measures of vaccination. Our results indicate the possibility of missed opportunities to vaccinate MSM. Gaps in implementing existing vaccination strategies must be addressed to increase hepatitis B vaccination coverage for MSM, especially in older age groups. |
Antiviral susceptibility of variant influenza A(H3N2)v viruses isolated in the United States from 2011 to 2013
Sleeman K , Mishin VP , Guo Z , Garten RJ , Balish A , Fry AM , Villanueva J , Stevens J , Gubareva LV . Antimicrob Agents Chemother 2014 58 (4) 2045-51 Since 2011, outbreaks caused by influenza A(H3N2) variant [A(H3N2)v] viruses have become a public health concern in the United States. The A(H3N2)v viruses share the A(H1N1)pdm09 M gene containing the marker of M2 blocker resistance, S31N, but do not contain any known molecular markers associated with resistance to neuraminidase (NA) inhibitors (NAIs). Using a fluorescent NA inhibition (NI) assay, the susceptibilities of recovered A(H3N2)v viruses (n = 168) to FDA-approved (oseltamivir and zanamivir) and other (peramivir, laninamivir, and A-315675) NAIs were assessed. All A(H3N2)v viruses tested, with the exception of a single virus strain, A/Ohio/88/2012, isolated from an untreated patient, were susceptible to the NAIs tested. The A/Ohio/88/2012 virus contained two rare substitutions, S245N and S247P, in the NA and demonstrated reduced inhibition by oseltamivir (31-fold) and zanamivir (66-fold) in the NI assay. Using recombinant NA (recNA) proteins, S247P was shown to be responsible for the observed altered NAI susceptibility, in addition to an approximately 60% reduction in NA enzymatic activity. The S247P substitution has not been previously reported as a molecular marker of reduced susceptibility to the NAIs. Using cell culture assays, the investigational antiviral drugs nitazoxanide, favipiravir, and fludase were shown to inhibit the replication of A(H3N2)v viruses, including the virus with the S247P substitution in the NA. This report demonstrates the importance of continuous monitoring of susceptibility of zoonotic influenza viruses to available and investigational antiviral drugs. |
Characterization of chronic hepatitis B cases among foreign-born persons in six population-based surveillance sites, United States 2001-2010
Liu SJ , Iqbal K , Shallow S , Speers S , Rizzo E , Gerard K , Poissant T , Klevens RM . J Immigr Minor Health 2014 17 (1) 7-12 National surveys indicate prevalence of chronic hepatitis B among foreign-born persons in the USA is 5.6 times higher than US-born. Centers for Disease Control and Prevention funded chronic hepatitis B surveillance in Emerging Infections Program sites. A case was any chronic hepatitis B case reported to participating sites from 2001 to 2010. Sites collected standardized demographic data on all cases. We tested differences between foreign- and US-born cases by age, sex, and pregnancy using Chi square tests. We examined trends by birth country during 2005-2010. Of 36,008 cases, 21,355 (59.3 %) reported birth in a country outside the USA, 2,323 (6.5 %) were US-born. Compared with US-born, foreign-born persons were 9.2 times more frequent among chronic hepatitis B cases. Foreign-born were more frequently female, younger, ever pregnant, and born in China. Percentages of cases among foreign-born persons were constant during 2005-2010. Our findings support information from US surveillance for Hepatitis B screening and vaccination efforts. |
Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010
Denniston MM , Jiles RB , Drobeniuc J , Klevens RM , Ward JW , McQuillan GM , Holmberg SD . Ann Intern Med 2014 160 (5) 293-+ BACKGROUND: Knowledge of the number of persons with chronic hepatitis C virus (HCV) infection in the United States is critical for public health and policy planning. OBJECTIVE: To estimate the prevalence of chronic HCV infection between 2003 and 2010 and to identify factors associated with this condition. DESIGN: Nationally representative household survey. SETTING: U.S. noninstitutionalized civilian population. PARTICIPANTS: 30 074 NHANES (National Health and Nutrition Examination Survey) participants between 2003 and 2010. MEASUREMENTS: Interviews to ascertain demographic characteristics and possible risks and exposures for HCV infection. Serum samples from participants aged 6 years or older were tested for antibody to HCV; if results were positive or indeterminate, the samples were tested for HCV RNA, which indicates current chronic infection. RESULTS: Based on 273 participants who tested positive for HCV RNA, the estimated prevalence of HCV infection was 1.0% (95% CI, 0.8% to 1.2%), corresponding to 2.7 million chronically infected persons (CI, 2.2 to 3.2 million persons) in the U. S. noninstitutionalized civilian population. Infected persons were more likely to be aged 40 to 59 years, male, and non-Hispanic black and to have less education and lower family income. Factors significantly associated with chronic HCV infection were illicit drug use (including injection drugs) and receipt of a blood transfusion before 1992; 49% of persons with HCV infection did not report either risk factor. LIMITATION: Incarcerated and homeless persons were not surveyed. CONCLUSION: This analysis estimated that approximately 2.7 million U. S. residents in the population sampled by NHANES have chronic HCV infection, about 500 000 fewer than estimated in a similar analysis between 1999 and 2002. These data underscore the urgency of identifying the millions of persons who remain infected and linking them to appropriate care and treatment. |
Cumulative risk of chlamydial infection among young women in Florida, 2000-2011
Peterman TA , Newman DR , Torrone E , Schmitt K , Shiver S . J Adolesc Health 2014 55 (2) 241-6 PURPOSE: Chlamydia trachomatis is a very common infection among young women in the United States; information on cumulative risk of infection is limited. We sought to estimate the cumulative risk of chlamydial infection for young women. METHODS: We measured cumulative risk of reported chlamydial infection for 14- to 34-year-old women in Florida between 2000 and 2011 using surveillance records and census estimates. We calculated reported infections per woman, analyzed first infections to get cumulative risk, and calculated risk of repeat infection over the 12-year period. RESULTS: There were 457,595 infections reported among 15- to 34-year-old women. Reports increased annually from 25,390 to 51,536. Nineteen-year-olds were at highest risk with 5.1 infections reported per 100 women in 2011. There were 341,671 different women infected. Among women aged 14-17 years in 2000, over 20% had at least one infection reported within 12 years, and among blacks, this risk was over 36%, and that underestimates risk because 18% of cases were missing race/ethnicity information. Repeat infections were common. Among 53,109 with chlamydia at the age of 15-20 years during 2000-2003, 36.7% had additional infections reported by 2011. CONCLUSIONS: More than one out of five women in Florida was reported as having chlamydia during her young-adult years; risk was highest for black women. True infection risks were likely much higher because many infections were not diagnosed or reported. Young women who had chlamydia were very likely to get reinfected. Rates of infection remain high despite years of screening. More information is needed on how to prevent chlamydial infection. |
Decline in tuberculosis among Mexico-born persons in the United States, 2000-2010
Baker BJ , Jeffries CD , Moonan PK . Ann Am Thorac Soc 2014 11 (4) 480-8 BACKGROUND: In 2010, Mexico was the most common (22.9%) country of origin for foreign-born persons with tuberculosis in the United States, and overall trends in tuberculosis morbidity are substantially influenced by the Mexico-born population. OBJECTIVES: To determine the risk of tuberculosis disease in the United States among the Mexico-born population. METHODS: Utilizing data from the United States National Tuberculosis Surveillance System and American Community Survey, we examined tuberculosis case counts and case rates stratified by years since United States entry and geographic proximity to the United States-Mexico border. We calculated trends in case rates over time measured by average annual percent change. RESULTS: The total tuberculosis case count (-14.5%) and annual tuberculosis case rate (average annual percent change -5.1%) declined among Mexico-born persons. Among newly arrived persons (tuberculosis diagnosis <1 year since United States entry), there was a decrease in tuberculosis cases (-60.4%), no change in tuberculosis case rate (average annual percent change 0.0%), and a decrease in population (-60.7%). Among non-recently arrived persons (>5 years since United States entry), there was an increase in tuberculosis cases (+3.4%), a decrease in tuberculosis case rate (average annual percent change -4.9%), and an increase in population (+62.7%). In 2010, 66.7% of Mexico-born cases were among non-recently arrived persons, compared to 51.1% in 2000. While border states reported the highest proportions (>15%) of tuberculosis cases that were Mexico-born, the highest Mexico-born-specific tuberculosis case rates (>20 per 100,000 population) were in states in the eastern and southeastern regions of the United States. CONCLUSIONS: The decline in tuberculosis cases among Mexico-born persons may be attributed to a decline in newly arrived persons from Mexico and a decreased tuberculosis case rate among non-recently arrived persons; the extent of the decline was dampened by an unchanged tuberculosis case rate among newly arrived persons from Mexico and a large increase in the non-recently arrived Mexico-born population. If current trends continue, tuberculosis morbidity among Mexico-born persons in the United States will be increasingly driven by the non-recently arrived population. |
Sunguru virus: a novel virus in the family Rhabdoviridae isolated from a chicken in north-western Uganda.
Ledermann JP , Zeidner N , Borland EM , Mutebi JP , Lanciotti RS , Miller BR , Lutwama JJ , Tendo JM , Andama V , Powers AM . J Gen Virol 2014 95 1436-1443 Sunguru virus (SUNV), a novel virus belonging to the highly diverse Rhabdoviridae family, was isolated from a domestic chicken in the district of Arua, Uganda in 2011. This is the first documented isolation of a rhabdovirus from a chicken. SUNV is related to, but distinct from, Boteke virus and other members of the unclassified Sandjimba group. The genome is 11,056 kb in length and contains the five core rhabdovirus genes plus an additional C gene (within the open reading frame of the phosphoprotein gene) and a small hydrophobic protein (between the matrix and glycoprotein genes). Inoculation of vertebrate cells resulted in significant growth, with a peak titer of 7.8 log10 PFU/mL observed in baby hamster kidney cells. Little to no growth was observed in invertebrate cells and in live mosquitoes, with Anopheles gambiae mosquitoes demonstrating a 47.4% infection rate in the body but no dissemination to the salivary glands; this suggests that this novel virus is not arthropod-borne like some other members of the family Rhabdoviridae. |
Time trends of polycyclic aromatic hydrocarbon exposure in New York city from 2001 to 2012: assessed by repeat air and urine samples
Jung KH , Liu B , Lovinsky-Desir S , Yan B , Camann D , Sjodin A , Li Z , Perera F , Kinney P , Chillrud S , Miller RL . Environ Res 2014 131c 95-103 BACKGROUND: Exposure to air pollutants including polycyclic aromatic hydrocarbons (PAH), and specifically pyrene from combustion of fuel oil, coal, traffic and indoor sources, has been associated with adverse respiratory health outcomes. However, time trends of airborne PAH and metabolite levels detected via repeat measures over time have not yet been characterized. We hypothesized that PAH levels, measured repeatedly from residential indoor and outdoor monitors, and childrens urinary concentrations of PAH metabolites, would decrease following policy interventions to reduce traffic-related air pollution. METHODS: Indoor PAH (particle- and gas-phase) were collected for two weeks prenatally (n=98), at age 5/6 years (n=397) and age 9/10 years (n=198) since 2001 and at all three age-points (n=27). Other traffic-related air pollutants (black carbon and PM2.5) were monitored indoors simultaneous with PAH monitoring at ages 5/6 (n=403) and 9/10 (n=257) between 2005 and 2012. One third of the homes were selected across seasons for outdoor PAH, BC and PM2.5 sampling. Using the same sampling method, ambient PAH, BC and PM2.5 also were monitored every two weeks at a central site between 2007 and 2012. PAH were analyzed as semivolatile PAH (e.g., pyrene; MW 178-206) ( summation operator8PAHsemivolatile: Including pyrene (PYR), phenanthrene (PHEN), 1-methylphenanthrene (1-MEPH), 2-methylphenanthrene (2-MEPH), 3-methylphenanthrene (3-MEPH), 9-methylphenanthrene (9-MEPH), 1,7-dimethylphenanthrene (1,7-DMEPH), and 3,6-dimethylphenanthrene (3,6-DMEPH)) and the sum of eight nonvolatile PAH ( summation operator8PAHnonvolatile: Including benzo[a]anthracene (BaA), chrysene/iso-chrysene (Chry), benzo[b]fluoranthene (BbFA), benzo[k]fluoranthene (BkFA), benzo[a]pyrene (BaP), indeno[1,2,3-c,d]pyrene (IP), dibenzo[a,h]anthracene (DahA), and benzo[g,h,i]perylene (BghiP); MW 228-278). A spot urine sample was collected from children at child ages 3, 5, 7 and 9 between 2001 and 2012 and analyzed for 10 PAH metabolites. RESULTS: Modest declines were detected in indoor BC and PM2.5 levels between 2005 and 2012 (Annual percent change [APC]=-2.08% [p=0.010] and -2.18% [p=0.059] for BC and PM2.5, respectively), while a trend of increasing pyrene levels was observed in indoor and outdoor samples, and at the central site during the comparable time periods (APC=4.81%, 3.77% and 7.90%, respectively; p<0.05 for all). No significant time trend was observed in indoor summation operator8PAHnonvolatile levels between 2005 and 2012; however, significant opposite trends were detected when analyzed seasonally (APC=-8.06% [p<0.01], 3.87% [p<0.05] for nonheating and heating season, respectively). Similarly, heating season also affected the annual trends (2005-2012) of other air pollutants: the decreasing BC trend (in indoor/outdoor air) was observed only in the nonheating season, consistent with dominating traffic sources that decreased with time; the increasing pyrene trend was more apparent in the heating season. Outdoor PM2.5 levels persistently decreased over time across the seasons. With the analyses of data collected over a longer period of time (2001-2012), a decreasing trend was observed in pyrene (APC=-2.76%; p<0.01), mostly driven by measures from the nonheating season (APC=-3.54%; p<0.01). In contrast, levels of pyrene and naphthalene metabolites, 1-hydroxypyrene and 2-naphthol, increased from 2001 to 2012 (APC=6.29% and 7.90% for 1-hydroxypyrene and 2-naphthol, respectively; p<0.01 for both). CONCLUSIONS: Multiple NYC legislative regulations targeting traffic-related air pollution may have led to decreases in summation operator8PAHnonvolatile and BC, especially in the nonheating season. Despite the overall decrease in pyrene over the 2001-2012 periods, a rise in pyrene levels in recent years (2005-2012), that was particularly evident for measures collected during the heating season, and 2-naphthol, indicates the contribution of heating oil combustion and other indoor sources to airborne pyrene and urinary 2-naphthol. |
Plasma polychlorinated biphenyl concentrations and immune function in postmenopausal women
Spector JT , De Roos AJ , Ulrich CM , Sheppard L , Sjodin A , Wener MH , Wood B , McTiernan A . Environ Res 2014 131c 174-180 BACKGROUND: Polychlorinated biphenyl (PCB) exposure has been associated with non-Hodgkin lymphoma in several studies, and the immune system is a potential mediator. OBJECTIVES: We analyzed associations of plasma PCBs with immune function measures. We hypothesized that higher plasma PCB concentrations are associated with lower immune function cross-sectionally, and that increases in PCB concentrations over a one year period are associated with decreases in immune function. METHODS: Plasma PCB concentrations and immune function [natural killer (NK) cell cytotoxicity and PHA-induced T-lymphocyte proliferation (PHA-TLP)] were measured at baseline and one year in 109 postmenopausal overweight women participating in an exercise intervention study in the Seattle, Washington (USA) area. Mixed models, with adjustment for body mass index and other potential confounders, were used to estimate associations of PCBs with immune function cross-sectionally and longitudinally. RESULTS: Associations of PCBs with immune function measures differed across groups of PCBs (e.g., medium- and high-chlorinated and dioxin-like [mono-ortho-substituted]) and by the time frame for the comparison (cross-sectional vs. longitudinal). Higher concentrations of medium- and high-chlorinated PCBs were associated with higher PHA-TLP cross-sectionally but not longitudinally. The mean decrease in 0.5microg/mL PHA-TLP/50.0pmol/g-lipid increase in dioxin-like PCBs over one year was 51.6 (95% confidence interval 2.7, 100.5; P=0.039). There was no association between plasma PCBs and NK cytotoxicity. CONCLUSIONS: These results do not provide strong evidence of impaired cellular immunity from PCB exposure. Larger longitudinal studies with greater variability in PCB exposures are needed to further examine temporal associations of PCBs with immune function. |
Revised surveillance case definition for HIV infection - United States, 2014
Selik RM , Mokotoff ED , Branson B , Owen SM , Whitmore S , Hall HI . MMWR Recomm Rep 2014 63 1-10 Following extensive consultation and peer review, CDC and the Council of State and Territorial Epidemiologists have revised and combined the surveillance case definitions for human immunodeficiency virus (HIV) infection into a single case definition for persons of all ages (i.e., adults and adolescents aged ≥13 years and children aged <13 years). The revisions were made to address multiple issues, the most important of which was the need to adapt to recent changes in diagnostic criteria. Laboratory criteria for defining a confirmed case now accommodate new multitest algorithms, including criteria for differentiating between HIV-1 and HIV-2 infection and for recognizing early HIV infection. A confirmed case can be classified in one of five HIV infection stages (0, 1, 2, 3, or unknown); early infection, recognized by a negative HIV test within 6 months of HIV diagnosis, is classified as stage 0, and acquired immunodeficiency syndrome (AIDS) is classified as stage 3. Criteria for stage 3 have been simplified by eliminating the need to differentiate between definitive and presumptive diagnoses of opportunistic illnesses. Clinical (nonlaboratory) criteria for defining a case for surveillance purposes have been made more practical by eliminating the requirement for information about laboratory tests. The surveillance case definition is intended primarily for monitoring the HIV infection burden and planning for prevention and care on a population level, not as a basis for clinical decisions for individual patients. CDC and the Council of State and Territorial Epidemiologists recommend that all states and territories conduct case surveillance of HIV infection using this revised surveillance case definition. |
Comparing study populations of men who have sex with men: evaluating consistency within repeat studies and across studies in the Seattle area using different recruitment methodologies
Burt RD , Oster AM , Golden MR , Thiede H . AIDS Behav 2014 18 Suppl 3 370-81 There is no gold standard for recruiting unbiased samples of men who have sex with men (MSM). To assess differing recruitment methods, we compared Seattle-area MSM samples from: venue-day-time sampling-based National HIV Behavioral Surveillance (NHBS) surveys in 2008 and 2011, random-digit-dialed (RDD) surveys in 2003 and 2006, and STD clinic patient data 2001-2011. We compared sociodemographics, sexual and drug-associated behavior, and HIV status and testing. There was generally good consistency between the two NHBS surveys and within STD clinic data across time. NHBS participants reported higher levels of drug-associated and lower levels of sexual risk than STD clinic patients. RDD participants differed from the other study populations in sociodemographics and some risk behaviors. While neither NHBS nor the STD clinic study populations may be representative of all MSM, both appear to provide consistent samples of MSM subpopulations across time that can provide useful information to guide HIV prevention. |
Clostridium difficile infection among children across diverse US geographic locations
Wendt JM , Cohen JA , Mu Y , Dumyati GK , Dunn JR , Holzbauer SM , Winston LG , Johnston HL , Meek JI , Farley MM , Wilson LE , Phipps EC , Beldavs ZG , Gerding DN , McDonald LC , Gould CV , Lessa FC . Pediatrics 2014 133 (4) 651-8 OBJECTIVE: Little is known about the epidemiology of Clostridium difficile infection (CDI) among children, particularly children ≤3 years of age in whom colonization is common but pathogenicity uncertain. We sought to describe pediatric CDI incidence, clinical presentation, and outcomes across age groups. METHODS: Data from an active population- and laboratory-based CDI surveillance in 10 US geographic areas during 2010-2011 were used to identify cases (ie, residents with C difficile-positive stool without a positive test in the previous 8 weeks). Community-associated (CA) cases had stool collected as outpatients or ≤3 days after hospital admission and no overnight health care facility stay in the previous 12 weeks. A convenience sample of CA cases were interviewed. Demographic, exposure, and clinical data for cases aged 1 to 17 years were compared across 4 age groups: 1 year, 2 to 3 years, 4 to 9 years, and 10 to 17 years. RESULTS: Of 944 pediatric CDI cases identified, 71% were CA. CDI incidence per 100 000 children was highest among 1-year-old (66.3) and white (23.9) cases. The proportion of cases with documented diarrhea (72%) or severe disease (8%) was similar across age groups; no cases died. Among the 84 cases interviewed who reported diarrhea on the day of stool collection, 73% received antibiotics during the previous 12 weeks. CONCLUSIONS: Similar disease severity across age groups suggests an etiologic role for C difficile in the high rates of CDI observed in younger children. Prevention efforts to reduce unnecessary antimicrobial use among young children in outpatient settings should be prioritized. |
Safety and immunogenicity of a plant-produced recombinant monomer hemagglutinin-based influenza vaccine derived from influenza A (H1N1)pdm09 virus: a Phase 1 dose-escalation study in healthy adults
Cummings JF , Guerrero ML , Moon JE , Waterman P , Nielsen RK , Jefferson S , Gross FL , Hancock K , Katz JM , Yusibov V . Vaccine 2014 32 (19) 2251-9 BACKGROUND: Novel influenza viruses continue to pose a potential pandemic threat worldwide. In recent years, plants have been used to produce recombinant proteins, including subunit vaccines. A subunit influenza vaccine, HAC1, based on recombinant hemagglutinin from the 2009 pandemic A/California/04/2009 (H1N1) strain of influenza virus, has been manufactured using a plant virus-based transient expression technology in Nicotiana benthamiana plants and demonstrated to be immunogenic and safe in pre-clinical studies (Shoji et al., 2011). METHODS: A first-in-human, Phase 1, single-center, randomized, placebo-controlled, single-blind, dose escalation study was conducted to investigate safety, reactogenicity and immunogenicity of an HAC1 formulation at three escalating dose levels (15mug, 45mug and 90mug) with and without Alhydrogel((R)), in healthy adults 18-50 years of age (inclusive). Eighty participants were randomized into six study vaccine groups, a saline placebo group and an approved monovalent H1N1 vaccine group. Recipients received two doses of vaccine or placebo (except for the monovalent H1N1 vaccine cohort, which received a single dose of vaccine, later followed by a dose of placebo). RESULTS: The experimental vaccine was safe and well tolerated, and comparable to placebo and the approved monovalent H1N1 vaccine. Pain and tenderness at the injection site were the only local solicited reactions reported following vaccinations. Nearly all adverse events were mild to moderate in severity. The HAC1 vaccine was also immunogenic, with the highest seroconversion rates, based on serum hemagglutination-inhibition and virus microneutralization antibody titers, in the 90mug non-adjuvanted HAC1 vaccine group after the second vaccine dose (78% and 100%, respectively). CONCLUSIONS: This is the first study demonstrating the safety and immunogenicity of a plant-produced subunit H1N1 influenza vaccine in healthy adults. The results support further clinical investigation of the HAC1 vaccine as well as demonstrate the feasibility of the plant-based technology for vaccine antigen production. |
Military healthcare providers reporting of adverse events following immunizations to the vaccine adverse event reporting system
Li R , McNeil MM , Pickering S , Pemberton MR , Duran LL , Collins LC , Nelson MR , Engler RJ . Mil Med 2014 179 (4) 435-41 OBJECTIVES: We studied military health care provider (HCP) practices regarding reporting of adverse events following immunization (AEFI). METHODS: A convenience sample of HCP was surveyed to assess familiarity with Vaccine Adverse Event Reporting System (VAERS), AEFI they were likely to report, methods used and preferred for reporting, and perceived barriers to reporting. We analyzed factors associated with HCP reporting AEFI to VAERS. RESULTS: A total of 547 surveys were distributed with 487 completed and returned for an 89% response rate. The percentage of HCP aware of VAERS (54%) varied by occupation. 47% of respondents identified knowledge of at least one AEFI with only 34% of these indicating that they had ever reported to VAERS. More serious events were more likely to be reported. Factors associated with HCP reporting AEFIs in bivariate analysis included HCP familiarity with filing a paper VAERS report, HCP familiarity with filing an electronic VAERS report, HCP familiarity with VAERS, and time spent on immunization tasks. In a multivariable analysis, only HCP familiarity with filing a paper VAERS report was statistically significant (Odds ratio = 115.3; p < 0.001). CONCLUSIONS: Specific educational interventions targeted to military HCP likely to see AEFIs but not currently filing VAERS reports may improve vaccine safety reporting practices. |
Economic evaluation of the routine childhood immunization program in the United States, 2009
Zhou F , Shefer A , Wenger J , Messonnier M , Wang LY , Lopez A , Moore M , Murphy TV , Cortese M , Rodewald L . Pediatrics 2014 133 (4) 577-85 OBJECTIVES: To evaluate the economic impact of the 2009 routine US childhood immunization schedule, including diphtheria and tetanus toxoids and acellular pertussis, Haemophilus influenzae type b conjugate, inactivated poliovirus, measles/mumps/rubella, hepatitis B, varicella, 7-valent pneumococcal conjugate, hepatitis A, and rotavirus vaccines; influenza vaccine was not included. METHODS: Decision analysis was conducted using population-based vaccination coverage, published vaccine efficacies, historical data on disease incidence before vaccination, and disease incidence reported during 2005 to 2009. Costs were estimated using the direct cost and societal (direct and indirect costs) perspectives. Program costs included vaccine, administration, vaccine-associated adverse events, and parent travel and work time lost. All costs were inflated to 2009 dollars, and all costs and benefits in the future were discounted at a 3% annual rate. A hypothetical 2009 US birth cohort of 4 261 494 infants over their lifetime was followed up from birth through death. Net present value (net savings) and benefit-cost ratios of routine childhood immunization were calculated. RESULTS: Analyses showed that routine childhood immunization among members of the 2009 US birth cohort will prevent approximately 42 000 early deaths and 20 million cases of disease, with net savings of $13.5 billion in direct costs and $68.8 billion in total societal costs, respectively. The direct and societal benefit-cost ratios for routine childhood vaccination with these 9 vaccines were 3.0 and 10.1. CONCLUSIONS: From both direct cost and societal perspectives, vaccinating children as recommended with these vaccines results in substantial cost savings. |
Impact of a targeted typhoid vaccination campaign following Cyclone Tomas, Republic of Fiji, 2010
Scobie HM , Nilles E , Kama M , Kool JL , Mintz E , Wannemuehler KA , Hyde TB , Dawainavesi A , Singh S , Korovou S , Jenkins K , Date K . Am J Trop Med Hyg 2014 90 (6) 1031-8 After a category 4 cyclone that caused extensive population displacement and damage to water and sanitation infrastructure in Fiji in March 2010, a typhoid vaccination campaign was conducted as part of the post-disaster response. During June-December 2010, 64,015 doses of typhoid Vi polysaccharide vaccine were administered to person's ≥ 2 years of age, primarily in cyclone-affected areas that were typhoid endemic. Annual typhoid fever incidence decreased during the post-campaign year (2011) relative to preceding years (2008-2009) in three subdivisions where a large proportion of the population was vaccinated (incidence rate ratios and 95% confidence intervals: 0.23, 0.13-0.41; 0.24, 0.14-0.41; 0.58, 0.40-0.86), and increased or remained unchanged in 12 subdivisions where little to no vaccination occurred. Vaccination played a role in reducing typhoid fever incidence in high-incidence areas after a disaster and should be considered in endemic settings, along with comprehensive control measures, as recommended by the World Health Organization. |
Reducing communication delays and improving quality of care with a tuberculosis laboratory information system in resource poor environments: a cluster randomized controlled trial
Blaya JA , Shin SS , Yagui M , Contreras C , Cegielski P , Yale G , Suarez C , Asencios L , Bayona J , Kim J , Fraser HS . PLoS One 2014 9 (4) e90110 BACKGROUND: Lost, delayed or incorrect laboratory results are associated with delays in initiating treatment. Delays in treatment for Multi-Drug Resistant Tuberculosis (MDR-TB) can worsen patient outcomes and increase transmission. The objective of this study was to evaluate the impact of a laboratory information system in reducing delays and the time for MDR-TB patients to culture convert (stop transmitting). METHODS: Setting: 78 primary Health Centers (HCs) in Lima, Peru. Participants lived within the catchment area of participating HCs and had at least one MDR-TB risk factor. The study design was a cluster randomized controlled trial with baseline data. The intervention was the e-Chasqui web-based laboratory information system. Main outcome measures were: times to communicate a result; to start or change a patient's treatment; and for that patient to culture convert. RESULTS: 1671 patients were enrolled. Intervention HCs took significantly less time to receive drug susceptibility test (DST) (median 11 vs. 17 days, Hazard Ratio 0.67 [0.62-0.72]) and culture (5 vs. 8 days, 0.68 [0.65-0.72]) results. The time to treatment was not significantly different, but patients in intervention HCs took 16 days (20%) less time to culture convert (p = 0.047). CONCLUSIONS: The eChasqui system reduced the time to communicate results between laboratories and HCs and time to culture conversion. It is now used in over 259 HCs covering 4.1 million people. This is the first randomized controlled trial of a laboratory information system in a developing country for any disease and the only study worldwide to show clinical impact of such a system. TRIAL REGISTRATION: ClinicalTrials.gov NCT01201941. |
High-throughput, luciferase-based reverse genetics systems for identifying inhibitors of Marburg and Ebola viruses.
Uebelhoer LS , Albarino CG , McMullan LK , Chakrabarti AK , Vincent JP , Nichol ST , Towner JS . Antiviral Res 2014 106 86-94 Marburg virus (MARV) and Ebola virus (EBOV), members of the family Filoviridae, represent a significant challenge to global public health. Currently, no licensed therapies exist to treat filovirus infections, which cause up to 90% mortality in human cases. To facilitate development of antivirals against these viruses, we established two distinct screening platforms based on MARV and EBOV reverse genetics systems that express secreted Gaussia luciferase (gLuc). The first platform is a mini-genome replicon to screen viral replication inhibitors using gLuc quantification in a BSL-2 setting. The second platform is complementary to the first and expresses gLuc as a reporter gene product encoded in recombinant infectious MARV and EBOV, thereby allowing for rapid quantification of viral growth during treatment with antiviral compounds. We characterized these viruses by comparing luciferase activity to virus production, and validated luciferase activity as an authentic real-time measure of viral growth. As proof of concept, we adapt both mini-genome and infectious virus platforms to high-throughput formats, and demonstrate efficacy of several antiviral compounds. We anticipate that both approaches will prove highly useful in the development of anti-filovirus therapies, as well as in basic research on the filovirus life cycle. |
Multilaboratory study of epidemiological cutoff values for detection of resistance in eight Candida species to fluconazole, posaconazole, and voriconazole
Espinel-Ingroff A , Pfaller MA , Bustamante B , Canton E , Fothergill A , Fuller J , Gonzalez GM , Lass-Florl C , Lockhart SR , Martin-Mazuelos E , Meis JF , Melhem MS , Ostrosky-Zeichner L , Pelaez T , Szeszs MW , St-Germain G , Bonfietti LX , Guarro J , Turnidge J . Antimicrob Agents Chemother 2014 58 (4) 2006-12 Although epidemiological cutoff values (ECVs) have been established for Candida spp. and the triazoles, they are based on MIC data from a single laboratory. We have established ECVs for eight Candida species and fluconazole, posaconazole, and voriconazole based on wild-type (WT) MIC distributions for isolates of C. albicans (n = 11,241 isolates), C. glabrata (7,538), C. parapsilosis (6,023), C. tropicalis (3,748), C. krusei (1,073), C. lusitaniae (574), C. guilliermondii (373), and C. dubliniensis (162). The 24-h CLSI broth microdilution MICs were collated from multiple laboratories (in Canada, Brazil, Europe, Mexico, Peru, and the United States). The ECVs for distributions originating from ≥6 laboratories, which included ≥95% of the modeled WT population, for fluconazole, posaconazole, and voriconazole were, respectively, 0.5, 0.06 and 0.03 mug/ml for C. albicans, 0.5, 0.25, and 0.03 mug/ml for C. dubliniensis, 8, 1, and 0.25 mug/ml for C. glabrata, 8, 0.5, and 0.12 mug/ml for C. guilliermondii, 32, 0.5, and 0.25 mug/ml for C. krusei, 1, 0.06, and 0.06 mug/ml for C. lusitaniae, 1, 0.25, and 0.03 mug/ml for C. parapsilosis, and 1, 0.12, and 0.06 mug/ml for C. tropicalis. The low number of MICs (<100) for other less prevalent species (C. famata, C. kefyr, C. orthopsilosis, C. rugosa) precluded ECV definition, but their MIC distributions are documented. Evaluation of our ECVs for some species/agent combinations using published individual MICs for 136 isolates (harboring mutations in or upregulation of ERG11, MDR1, CDR1, or CDR2) and 64 WT isolates indicated that our ECVs may be useful in distinguishing WT from non-WT isolates. |
Non-human primate models of hormonal contraception and HIV
McNicholl JM , Henning TC , Vishwanathan SA , Kersh EN . Am J Reprod Immunol 2014 71 (6) 513-22 PROBLEM: Recent concerns that hormonal contraception (HC) may increase risk of HIV acquisition has led to keen interest in using non-human primates (NHP) to understand the underlying mechanism and the magnitude of the risk. This is, in part, because some experiments which would be difficult or logistically impossible in women are more easily conducted in NHP. METHOD OF STUDY: NHP models of HIV can inform HIV acquisition and pathogenesis research and identify and evaluate biomedical preventions and treatments for HIV/AIDS. Widely used species include rhesus, pigtail, and cynomolgous macaques. RESULTS: This paper reviews past, current and proposed NHP research around the intersection of HIV and HC. CONCLUSION: NHP research may lead to the identification of hormonally regulated biomarkers that correlate with HIV-acquisition risk, to a ranking of existing or next-generation HC along an HIV-acquisition risk profile, and inform research around new biomedical preventions for HIV. |
Normal laboratory reference intervals among healthy adults screened for a HIV pre-exposure prophylaxis clinical trial in Botswana
Segolodi TM , Henderson FL , Rose CE , Turner KT , Zeh C , Fonjungo PN , Niska R , Hart C , Paxton LA . PLoS One 2014 9 (4) e93034 INTRODUCTION: Accurate clinical laboratory reference values derived from a local or regional population base are required to correctly interpret laboratory results. In Botswana, most reference intervals used to date are not standardized across clinical laboratories and are based on values derived from populations in the United States or Western Europe. METHODS: We measured 14 hematologic and biochemical parameters of healthy young adults screened for participation in the Botswana HIV Pre-exposure Prophylaxis Study using tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) (TDF2 Study). Reference intervals were calculated using standard methods, stratified by gender, and compared with the site-derived reference values used for the TDF2 study (BOTUSA ranges), the Division of AIDS (DAIDS) Grading Table for Adverse Events, the Botswana public health laboratories, and other regional references. RESULTS: Out of 2533 screened participants, 1786 met eligibility criteria for participation in study and were included in the analysis. Our reference values were comparable to those of the Botswana public health system except for amylase, blood urea nitrogen (BUN), phosphate, total and direct bilirubin. Compared to our reference values, BOTUSA reference ranges would have classified participants as out of range for some analytes, with amylase (50.8%) and creatinine (32.0%) producing the highest out of range values. Applying the DAIDS toxicity grading system to the values would have resulted in 45 and 18 participants as having severe or life threatening values for amylase and hemoglobin, respectively. CONCLUSION: Our reference values illustrate the differences in hematological and biochemical analyte ranges between African and Western populations. Thus, the use of western-derived reference laboratory values to screen a group of Batswana adults resulted in many healthy people being classified as having out-of-range blood analytes. The need to establish accurate local or regional reference values is apparent and we hope our results can be used to that end in Botswana. |
Quantification of 21 metabolites of methylnaphthalenes and polycyclic aromatic hydrocarbons in human urine
Li Z , Romanoff LC , Trinidad DA , Pittman EN , Hilton D , Hubbard K , Carmichael H , Parker J , Calafat AM , Sjodin A . Anal Bioanal Chem 2014 406 (13) 3119-29 Polycyclic aromatic hydrocarbons (PAHs) and their alkylated derivatives, such as methylnaphthalenes (MeNs), are harmful pollutants ubiquitously present in the environment. Exposure to PAHs has been linked to a variety of adverse health effects and outcomes, including cancer. Alkyl PAHs have been proposed as petrogenic source indicators because of their relatively high abundance in unburned petroleum products. We report a method to quantify 11 urinary methylnaphthols (Me-OHNs), metabolites of 1- and 2-methylnaphthalenes, and 10 monohydroxy PAH metabolites (OH-PAHs), using automated liquid-liquid extraction and isotope dilution gas chromatography tandem mass spectrometry (GC-MS/MS). After spiking urine (1 mL) with 13C-labeled internal standards, the conjugated target analytes were hydrolyzed enzymatically in the presence of ascorbic acid. Then, their free species were preconcentrated into 20 % toluene in pentane, derivatized and quantified by GC-MS/MS. The 11 Me-OHNs eluted as 6 distinct chromatographic peaks, each representing 1 - 3 isomers. Method detection limits were 1.0- 41 pg/mL and the coefficients of variation in quality control materials were 4.7 - 19 %. The method was used to analyze two National Institute of Standards and Technology's Standard Reference Materials(R) and samples from 30 smokers and 30 non-smokers. Geometric mean concentrations were on average 37 (Me-OHNs) and 9.0 (OH-PAHs) fold higher in smokers than in non-smokers. These findings support the usefulness of Me-OHNs as potential biomarkers of non-occupational exposure to MeNs and sources containing MeNs. |
Evaluation of a latex agglutination assay for the identification of Burkholderia pseudomallei and Burkholderia mallei
Duval BD , Elrod MG , Gee JE , Chantratita N , Tandhavanant S , Limmathurotsakul D , Hoffmaster AR . Am J Trop Med Hyg 2014 90 (6) 1043-6 Cases of melioidosis and glanders are rare in the United States, but the etiologic agents of each disease (Burkholderia pseudomallei and Burkholderia mallei, respectively) are classified as Tier 1 select agents because of concerns about their potential use as bioterrorism agents. A rapid, highly sensitive, and portable assay for clinical laboratories and field use is required. Our laboratory has further evaluated a latex agglutination assay for its ability to identify B. pseudomallei and B. mallei isolates. This assay uses a monoclonal antibody that specifically recognizes the capsular polysaccharide produced by B. pseudomallei and B. mallei, but is absent in closely related Burkholderia species. A total of 110 B. pseudomallei and B. mallei were tested, and 36 closely related Burkholderia species. The latex agglutination assay was positive for 109 of 110 (99.1% sensitivity) B. pseudomallei and B. mallei isolates tested. |
Alternative splice forms of CTLA-4 induced by antisense mediated splice-switching influences autoimmune diabetes susceptibility in NOD mice
Mourich DV , Oda SK , Schnell FJ , Crumley SL , Hauck LL , Moentenich CA , Marshall NB , Hinrichs DJ , Iversen PL . Nucleic Acid Ther 2014 24 (2) 114-26 Activated and regulatory T cells express the negative co-stimulatory molecule cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) that binds B7 on antigen-presenting cells to mediate cellular responses. Single nucleotide polymorphisms in the CTLA-4 gene have been found to affect alternative splicing and are linked to autoimmune disease susceptibility or resistance. Increased expression of a soluble splice form (sCTLA-4), lacking the transmembrane domain encoded by exon 3, has been shown to accelerate autoimmune pathology. In contrast, an exon 2-deficient form lacking the B7 ligand binding domain (liCTLA-4), expressed by diabetes resistant mouse strains has been shown to be protective when expressed as a transgene in diabetes susceptible non-obese diabetic (NOD) mice. We sought to employ an antisense-targeted splice-switching approach to independently produce these CTLA-4 splice forms in NOD mouse T cells and observe their relative impact on spontaneous autoimmune diabetes susceptibility. In vitro antisense targeting of the splice acceptor site for exon 2 produced liCTLA-4 while targeting exon 3 produced the sCTLA-4 form in NOD T cells. The liCTLA-4 expressing T cells exhibited reduced activation, proliferation and increased adhesion to intercellular adhesion molecule-1 (ICAM-1) similar to treatment with agonist alpha-CTLA-4. Mice treated to produce liCTLA-4 at the time of elevated blood glucose levels exhibited a significant reduction in the incidence of insulitis and diabetes, whereas a marked increase in the incidence of both was observed in animals treated to produce sCTLA-4. These findings provide further support that alternative splice forms of CTLA-4 affects diabetes susceptibility in NOD mice and demonstrates the therapeutic utility of antisense mediated splice-switching for modulating immune responses. |
Comparison of fecal occult blood tests for colorectal cancer screening in an Alaska Native population with high prevalence of Helicobacter pylori infection, 2008-2012
Redwood D , Provost E , Asay E , Roberts D , Haverkamp D , Perdue D , Bruce MG , Sacco F , Espey D . Prev Chronic Dis 2014 11 E56 INTRODUCTION: Alaska Native colorectal cancer (CRC) incidence and mortality rates are the highest of any ethnic/racial group in the United States. CRC screening using guaiac-based fecal occult blood tests (gFOBT) are not recommended for Alaska Native people because of false-positive results associated with a high prevalence of Helicobacter pylori-associated hemorrhagic gastritis. This study evaluated whether the newer immunochemical FOBT (iFOBT) resulted in a lower false-positive rate and higher specificity for detecting advanced colorectal neoplasia than gFOBT in a population with elevated prevalence of H. pylori infection. METHODS: We used a population-based sample of 304 asymptomatic Alaska Native adults aged 40 years or older undergoing screening or surveillance colonoscopy (April 2008-January 2012). RESULTS: Specificity differed significantly (P < .001) between gFOBT (76%; 95% CI, 71%-81%) and iFOBT (92%; 95% CI, 89%-96%). Among H. pylori-positive participants (54%), specificity of iFOBT was even higher (93% vs 69%). Overall, sensitivity did not differ significantly (P = .73) between gFOBT (29%) and iFOBT (36%). Positive predictive value was 11% for gFOBT and 32% for iFOBT. CONCLUSION: The iFOBT had a significantly higher specificity than gFOBT, especially in participants with current H. pylori infection. The iFOBT represents a potential strategy for expanding CRC screening among Alaska Native and other populations with elevated prevalence of H. pylori, especially where access to screening endoscopy is limited. |
Continuous sequential boundaries for vaccine safety surveillance
Li R , Stewart B , Weintraub E , McNeil MM . Stat Med 2014 33 (19) 3387-97 Various recently developed sequential methods have been used to detect signals for post-marketing surveillance in drug and vaccine safety. Among these, the maximized sequential probability ratio test (MaxSPRT) has been used to detect elevated risks of adverse events following vaccination using large healthcare databases. However, a limitation of MaxSPRT is that it only provides a time-invariant flat boundary. In this study, we propose the use of time-varying boundaries for controlling how type I error is distributed throughout the surveillance period. This is especially useful in two scenarios: (i) when we desire generally larger sample sizes before a signal is generated, for example, when early adopters are not representative of the larger population; and (ii) when it is desired for a signal to be generated as early as possible, for example, when the adverse event is considered rare but serious. We consider four specific time-varying boundaries (which we call critical value functions), and we study their statistical power and average time to signal detection. The methodology we present here can be viewed as a generalization or flexible extension of MaxSPRT. |
Vital Signs: births to teens aged 15-17 years - United States, 1991-2012
Cox S , Pazol K , Warner L , Romero L , Spitz A , Gavin L , Barfield W . MMWR Morb Mortal Wkly Rep 2014 63 (14) 312-8 BACKGROUND: Teens who give birth at age 15-17 years are at increased risk for adverse medical and social outcomes of teen pregnancy. METHODS: To examine trends in the rate and proportion of births to teens aged 15-19 years that were to teens aged 15-17 years, CDC analyzed 1991-2012 National Vital Statistics System data. National Survey of Family Growth (NSFG) data from 2006-2010 were used to examine sexual experience, contraceptive use, and receipt of prevention opportunities among female teens aged 15-17 years. RESULTS: During 1991-2012, the rate of births per 1,000 teens declined from 17.9 to 5.4 for teens aged 15 years, 36.9 to 12.9 for those aged 16 years, and 60.6 to 23.7 for those aged 17 years. In 2012, the birth rate per 1,000 teens aged 15-17 years was higher for Hispanics (25.5), non-Hispanic blacks (21.9), and American Indians/Alaska Natives (17.0) compared with non-Hispanic whites (8.4) and Asians/Pacific Islanders (4.1). The rate also varied by state, ranging from 6.2 per 1,000 teens aged 15-17 years in New Hampshire to 29.0 in the District of Columbia. In 2012, there were 86,423 births to teens aged 15-17 years, accounting for 28% of all births to teens aged 15-19 years. This percentage declined from 36% in 1991 to 28% in 2012 (p<0.001). NSFG data for 2006-2010 indicate that although 91% of female teens aged 15-17 years received formal sex education on birth control or how to say no to sex, 24% had not spoken with parents about either topic; among sexually experienced female teens, 83% reported no formal sex education before first sex. Among currently sexually active female teens (those who had sex within 3 months of the survey) aged 15-17 years, 58% used clinical birth control services in the past 12 months, and 92% used contraception at last sex; however, only 1% used the most effective reversible contraceptive methods. CONCLUSIONS: Births to teens aged 15-17 years have declined but still account for approximately one quarter of births to teens aged 15-19 years. Implications for public health practice: These data highlight opportunities to increase younger teens exposure to interventions that delay initiation of sex and provide contraceptive services for those who are sexually active; these strategies include support for evidence-based programs that reach youths before they initiate sex, resources for parents in talking to teens about sex and contraception, and access to reproductive health-care services. |
Brief interventions for illicit drug use among peripartum women
Farr SL , Hutchings YL , Ondersma SJ , Creanga AA . Am J Obstet Gynecol 2014 211 (4) 336-43 We review the evidence and identify limitations of the current literature on the effectiveness of brief interventions (≤5 intervention sessions) on illicit drug use, treatment enrollment/retention, and pregnancy outcomes among pregnant and postpartum women; and consider this evidence in the context of the broader brief intervention literature. Among four published studies identified via systematic review and meeting a priori quality criteria, we found limited, yet promising evidence of the benefit of brief interventions to reduce illicit drug use among postpartum women. Two of the four randomized controlled trials (RCTs) tested similar computer-delivered single-session interventions; both demonstrate effects on postpartum drug use. Neither of the two RCTs that assessed treatment utilization found differences between intervention and control groups. Studies examining brief interventions for smoking and alcohol use among pregnant women, and for illicit drug use in the general adult population, have shown small but statistically significant results of the effectiveness of such intervention. Larger studies, those that examine the effect of assessment alone on illicit drug use, and those that use technology-delivered brief interventions are needed to assess the effectiveness of brief interventions for drug use in the peripartum period. |
Emergency department predictors of posttraumatic stress reduction for trauma-exposed individuals with and without an early intervention
Price M , Kearns M , Houry D , Rothbaum BO . J Consult Clin Psychol 2014 82 (2) 336-41 OBJECTIVE: Recent data have supported the use of an early exposure intervention to promote a reduction in acute stress and posttraumatic stress disorder (PTSD) symptoms after trauma exposure. The present study explored a comprehensive predictive model that included history of trauma exposure, dissociation at the time of the trauma and early intervention, and physiological responses (cortisol and heart rate) to determine which variables were most indicative of reduced PTSD symptoms for an early intervention or treatment as usual. METHOD: Participants (n = 137) were randomly assigned to the early intervention condition (n = 68) or assessment-only condition (n = 69) while receiving care at the emergency department of a Level 1 trauma center. Follow-up assessments occurred at 4 and 12 weeks posttrauma. RESULTS: Findings suggested that dissociation at the time of the 1st treatment session was associated with reduced response to the early intervention. No other predictors were associated with treatment response. For treatment as usual, cortisol levels at the time of acute care and dissociation at the time of the traumatic event were positively associated with PTSD symptoms. CONCLUSIONS: Dissociation at the time at which treatment starts may indicate poorer response to early intervention for PTSD. Similarly, dissociation at the time of the event was positively related to PTSD symptoms in those who received treatment as usual. |
Genetic variants in the major histocompatibility complex class I and class II genes are associated with diisocyanate-induced Asthma.
Yucesoy B , Johnson VJ , Lummus ZL , Kashon ML , Rao M , Bannerman-Thompson H , Frye B , Wang W , Gautrin D , Cartier A , Boulet LP , Sastre J , Quirce S , Tarlo SM , Germolec DR , Luster MI , Bernstein DI . J Occup Environ Med 2014 56 (4) 382-7 OBJECTIVE: To investigate the association between single nucleotide polymorphisms (SNPs) located across the major histocompatibility complex and susceptibility to diisocyanate-induced asthma (DA). METHODS: The study population consisted of 140 diisocyanate-exposed workers. Genotyping was performed using the Illumina GoldenGate major histocompatibility complex panels. RESULTS: The HLA-E rs1573294 and HLA-DPB1 rs928976 SNPs were associated with an increased risk of DA under dominant (odds ratio [OR], 6.27; 95% confidence interval [CI], 2.37 to 16.6; OR, 2.79, 95% CI, 0.99 to 7.81, respectively) and recessive genetic models (OR, 6.27, 95% CI, 1.63 to 24.13; OR, 10.10, 95% CI, 3.16 to 32.33, respectively). The HLA-B rs1811197, HLA-DOA rs3128935, and HLA-DQA2 rs7773955 SNPs conferred an increased risk of DA in a dominant model (OR, 7.64, 95% CI, 2.25 to 26.00; OR, 19.69, 95% CI, 2.89 to 135.25; OR, 8.43, 95% CI, 3.03 to 23.48, respectively). CONCLUSION: These results suggest that genetic variations within HLA genes play a role in DA risk. |
Respiratory manganese particle size, time-course and neurobehavioral outcomes in workers at a manganese alloy production plant
Park RM , Bouchard MF , Baldwin M , Bowler R , Mergler D . Neurotoxicology 2014 45 276-84 The progression of manganism with chronic exposure to airborne manganese (Mn) is not well understood. Here, we further investigate the findings on exposure and neurobehavioral outcomes of workers from a silico- and ferromanganese production plant and non-exposed workers from the same community in 1990 and 2004, using a variety of exposure metrics that distinguish particle size and origin within the range of respirable airborne exposures. Mn exposure matrices for large respirable particulate (Mn-LRP, dust) and small respirable particulate (Mn-SRP, fume), based on process origins, were used together with detailed work histories since 1973 (plant opening), to construct exposure metrics including burdens and cumulative burdens with various clearance half-lives. For three out of eight 1990 neurobehavioral tests analyzed with linear regression models, duration of Mn exposure was the best predictor: Luria-Nebraska Neuropsychological Battery - Motor Scale, Trail-Making B and Finger Tapping. The Luria-Nebraska Motor Scale had the strongest association (t approximately 5.0, p<10-6). For outcomes on three other tests, the duration and Mn-SRP metrics were comparable: Trail Making Test A, Cancellation H and Stroop Color-Word Test (color/word subtest). Delayed Word Recall was best predicted by Mn-SRP (based on square root or truncated air-concentrations). The Word score on the Stroop Color-Word Test was the only outcome for which Mn-LRP was the leading predictor (t=-2.92, p=0.003), while performance on the WAIS-R Digit Span Test was not significantly predicted by any metric. For outcomes evaluated in both 1990 and 2004, a mixed-effect linear regression model was used to examine estimates of within-individual trends. Duration and Mn-SRP were associated with performance on the Luria-Nebraska Motor Scale, as well as with other outcomes that appeared to have both reversible and progressive features, including Trail Making A and B, Cancellation H and Delayed Word Recall. With the mixed-effect model, Digit Span exhibited a significant irreversible association with exposure duration (t=-2.34, p=0.021) and Mn-SRP (square root; t=-2.38, p=0.019) metrics. The strong prediction using duration of exposure is consistent with effective homeostatic regulation of tissue-level Mn in the observed exposure range of respirable Mn (< 0.2mg/m3). |
Regional variation in the correlation of antibody and T-cell responses to Trypanosoma cruzi
Martin DL , Marks M , Galdos-Cardenas G , Gilman RH , Goodhew B , Ferrufino L , Halperin A , Sanchez G , Verastegui M , Escalante P , Naquira C , Levy MZ , Bern C . Am J Trop Med Hyg 2014 90 (6) 1074-81 Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major cause of morbidity and mortality in Central and South America. Geographic variations in the sensitivity of serologic diagnostic assays to T. cruzi may reflect differences in T. cruzi exposure. We measured parasite-specific T-cell responses among seropositive individuals in two populations from South America with widely varying antibody titers against T. cruzi. Antibody titers among seropositive individuals were significantly lower in Arequipa, Peru compared with Santa Cruz, Bolivia. Similarly, the proportion of seropositive individuals with positive T-cell responses was lower in Peru than Bolivia, resulting in overall lower frequencies of interferon-gamma (IFNgamma) -secreting cells from Peruvian samples. However, the magnitude of the IFNgamma response was similar among the IFNgamma responders in both locations. These data indicate that immunological discrepancies based on geographic region are reflected in T-cell responses as well as antibody responses. |
Toxoplasma gondii seroprevalence in the United States 2009-2010 and comparison with the past two decades
Jones JL , Kruszon-Moran D , Rivera H , Price C , Wilkins PP . Am J Trop Med Hyg 2014 90 (6) 1135-9 Toxoplasma gondii is a ubiquitous parasite that can cause neurologic and ocular disease. We tested sera from 7,072 people ≥ 6 years of age in the 2009-2010 National Health and Nutrition Examination Survey (NHANES) for immunoglobulin G antibodies and compared these results with two previous NHANES surveys. The overall T. gondii antibody seroprevalence among persons ≥ 6 years of age in 2009-2010 was 13.2% (95% confidence limit [CL] 11.8%, 14.5%) and age-adjusted seroprevalence was 12.4% (95% CL 11.1%, 13.7%); age-adjusted seroprevalence among women 15-44 years of age was 9.1% (95% CL 7.2%, 11.1%). In U.S. born persons 12-49 years of age, the age-adjusted T. gondii seroprevalence decreased from 14.1% (95% CL 12.7%, 15.5%) in NHANES III (1988-1994) to 9.0% (95% CL 7.6%, 10.5%) in NHANES 1999-2004 to 6.7% (95% CL 5.3%, 8.2%) in NHANES 2009-2010 (P < 0.001 linear trend). Although T. gondii antibody presence is still relatively common, the prevalence in the United States has continued to decline. |
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