Beta-diversity metrics of the upper digestive tract microbiome are associated with body mass index.
Lin SW , Freedman ND , Shi J , Gail MH , Vogtmann E , Yu G , Klepac-Ceraj V , Paster BJ , Dye BA , Wang GQ , Wei WQ , Fan JH , Qiao YL , Dawsey SM , Abnet CC . Obesity (Silver Spring) 2015 23 (4) 862-9 OBJECTIVE: Studies of the fecal microbiome have implicated the gut microbiota in obesity, but few studies have examined the microbial diversity at other sites. The association between obesity and the upper gastrointestinal (UGI) microbial diversity was explored. METHODS: The UGI microbiome of 659 healthy Chinese adults with a measured body mass index (BMI) range of 15.0 to 35.7 was characterized using the 16S rRNA gene DNA microarray (HOMIM). RESULTS: In multivariate-adjusted models, alpha diversity was not associated with BMI. However, beta diversity, assessed by principal coordinate vectors generated from an unweighted UniFrac distance matrix of pairwise comparisons, was associated with BMI (third and fourth vectors, P = 0.01 and P = 0.03, respectively). Moreover, beta diversity, assessed by cluster membership (three clusters), was also associated with BMI; individuals in the first cluster [median BMI 22.35, odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.05-4.34] and second cluster [median BMI 22.55, OR = 0.26, 95% CI = 0.09-0.75] were significantly less likely to be obese (BMI ≥ 27.5) than those in the third cluster (median BMI 23.59). CONCLUSIONS: A beta-diversity metric of the UGI microbiome is associated with a four fold difference in obesity risk in this Asian population. Future studies should address whether the UGI microbiome plays a causal role in obesity. |
Predictors of poor mental and physical health status among patients with chronic hepatitis C infection: the Chronic Hepatitis Cohort Study (CHeCS)
Boscarino JA , Lu M , Moorman AC , Gordon SC , Rupp LB , Spradling PR , Teshale EH , Schmidt MA , Vijayadeva V , Holmberg SD . Hepatology 2015 61 (3) 802-11 Our objective was to assess the extent and risk factors for depression and poor physical health among patients with chronic hepatitis C virus (HCV) infection. We surveyed HCV-infected patients seen at four large healthcare systems participating in the Chronic Hepatitis Cohort Study (CHeCS). Survey data included demographics, depression and physical health measures, substance use history, current social support, recent stressor exposures, and, from the electronic medical record, treatment history, and Charlson Comorbidity Index scores. There were 4,781 respondents, who were a mean of 56.7 years old, 71% White, and 57% male. Altogether, 51.4% reported past injection drug use, 33.9% were current smokers, and 17.7% had abused alcohol in the previous year. Additionally, 47.4% had been previously treated for HCV and 14.8% had a 12-week sustained viral response (SVR) following HCV therapy. Overall, 29.7% of patients met criteria for current depression and 24.6% were in poor physical health. In multivariate analyses, significant predictors of depression and poor health included: male gender (versus female, odds ratios [ORs], 0.70 and 0.81), Black race (versus white, ORs, 0.60 and 0.61), having education less than high school (versus college, ORs, 1.81 and 1.54), being employed (versus not, ORs, 0.36 and 0.25), having high life stressors (versus low, ORs, 2.44 and 1.64), having low social support (versus high, ORs = 2.78 and 1.40), and having high Charlson scores (versus none, ORs = 1.58 and 2.12). Achieving a 12-week SVR was found to be protective for depression. CONCLUSION: This large survey of U.S. HCV patients indicates the extent of adverse health behaviors and mental and physical comorbidities among these patients. |
Preventing premature deaths from breast and cervical cancer among underserved women in the United States: insights gained from a national cancer screening program
White MC , Wong FL . Cancer Causes Control 2015 26 (5) 805-9 This commentary highlights some of the valuable insights gained from a special collection of papers that utilized data from the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) and appear in this special issue. The data and experiences of the NBCCEDP can inform the identification of new opportunities and directions for meeting the cancer screening needs of underserved women in a complex and changing health care environment. |
Factors associated with overall survival prostate cancer in Florida: a multilevel analysis
Xiao H , Tan F , Adunlin G , Ali AA , Goovaerts P , Gwede CK , Huang Y . J Health Care Poor Underserved 2015 26 (1) 266-77 OBJECTIVE: To investigate individual and contextual factors contributing to overall prostate cancer (PCa) survival in Florida. METHODS: A random sample of 6,457 PCa cases diagnosed between 10/1/2001 and 12/31/2007 was extracted from Florida Cancer Data System. Comorbidity was computed following Elixhauser Index. Survival probability curve was generated using Kaplan-Meier method. The Wei, Lin, and Weissfel model was used for the multivariate analysis. RESULTS: Older age at diagnosis was associated with shorter time to death. Current smokers had a higher hazard rate than non-current smokers. Higher hazard of overall mortality was associated with being diagnosed with advanced stage compared with localized stage and having poorly-differentiated tumor compared with well-moderately differentiated tumor. No definitive treatment, radiation alone, and hormone alone were significantly associated with elevated hazard rate compared with surgery. Fifteen comorbidities were significantly associated with shorter time-to-death. CONCLUSIONS: Effective control of comorbidity in PCa patients should help improve life expectancy and lead to prolonged survival. |
Filtration markers as predictors of ESRD and mortality in southwestern American Indians with type 2 diabetes
Foster MC , Inker LA , Hsu CY , Eckfeldt JH , Levey AS , Pavkov ME , Myers BD , Bennett PH , Kimmel PL , Vasan RS , Coresh J , Nelson RG . Am J Kidney Dis 2015 66 (1) 75-83 BACKGROUND: A growing number of serum filtration markers are associated with mortality and end-stage renal disease (ESRD) in adults. Whether beta-trace protein (BTP) and beta2-microglobulin (B2M) are associated with these outcomes in adults with type 2 diabetes is not known. STUDY DESIGN: Longitudinal cohort study. SETTING & PARTICIPANTS: 250 Pima Indians with type 2 diabetes (69% women; mean age, 42 years; mean diabetes duration, 11 years). PREDICTORS: Serum BTP, B2M, and glomerular filtration rate measured by iothalamate clearance (mGFR) or estimated using creatinine (eGFRcr) or cystatin C level (eGFRcys). OUTCOMES & MEASUREMENTS: Incident ESRD and all-cause mortality through December 2013. HRs were reported per interquartile range decrease of the inverse of BTP and B2M (1/BTP and 1/B2M) using Cox regression. Improvement in risk prediction with the addition of BTP or B2M level to established markers (eGFRcys with mGFR or eGFRcr) was evaluated using C statistics, continuous net reclassification improvement, and relative integrated discrimination improvement (RIDI). RESULTS: During a median follow-up of 14 years, 69 participants developed ESRD and 95 died. Both novel markers were associated with ESRD in multivariable models. BTP level remained statistically significant after further adjustment for mGFR (1/BTP, 1.53 [95% CI, 1.01-2.30]; 1/B2M, 1.54 [95% CI, 0.98-2.42]). B2M level was associated with mortality in multivariable models and after further adjustment for mGFR (HR, 2.12; 95% CI, 1.38-3.26). The addition of B2M level to established markers increased the C statistic for mortality but only weakly when assessed by either continuous net reclassification improvement or RIDI; none was improved for ESRD by the addition of these markers. LIMITATIONS: Small sample size, single measurements of markers. CONCLUSIONS: In Pima Indians with type 2 diabetes, BTP and, to a lesser extent, B2M levels were associated with ESRD. B2M level was associated with mortality after adjustment for traditional risk factors and established filtration markers. Further studies are warranted to confirm whether inclusion of B2M level in a multimarker approach leads to improved risk prediction for mortality in this population. |
Hip osteoarthritis and the risk of all-cause and disease-specific mortality in older women: population-based cohort study
Barbour KE , Lui LY , Nevitt MC , Murphy LB , Helmick CG , Theis KA , Hochberg MC , Lane NE , Hootman JM , Cauley JA . Arthritis Rheumatol 2015 67 (7) 1798-805 OBJECTIVES: Determine the risk of all-cause and disease-specific mortality among older women with hip OA and identify mediators in the causal pathway. METHODS: Data were from the Study of Osteoporotic Fractures, a US population-based cohort study of 9704 white women, aged ≥65 years. The analytic sample included women with hip radiographs at baseline (N=7,889) and year 8 (N=5,749). Mortality was confirmed through October 2013 by death certificates and hospital discharge summaries. Radiographic hip OA (RHOA) was defined as having Croft grade ≥2 in at least 1 hip (definite joint space narrowing or osteophytes plus 1 other radiographic feature). RESULTS: Mean follow-up time was 16.1 +/-6.2 years. Baseline and year 8 prevalence of RHOA was 8.0% and 11.0%, respectively. Cumulative incidence (proportion of deaths during study period) was 67.7% for all-cause mortality, 26.3% for cardiovascular disease (CVD) mortality, 11.7% for cancer mortality, 1.9% for gastrointestinal disease mortality, and 27.8% for all other mortality causes. RHOA was associated with an increased risk of all-cause (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.05-1.24), and CVD (HR, 1.24; 95% CI, 1.09-1.41) mortality adjusted for age, body mass index, education, smoking, health status, diabetes, and stroke. These associations were partially explained by physical function (mediating variable). CONCLUSION: RHOA was associated with an increased risk of all-cause and CVD mortality among older white women followed for 16 years. Dissemination of evidence-based physical activity and self-management interventions for hip OA in community and clinical settings can improve physical function and might also contribute to lower mortality. |
Incidence and prevalence of systemic lupus erythematosus among Arab and Chaldean Americans in southeastern Michigan: the Michigan Lupus Epidemiology and Surveillance Program
Housey M , DeGuire P , Lyon-Callo S , Wang L , Marder W , McCune WJ , Helmick CG , Gordon C , Dhar JP , Leisen J , Somers EC . Am J Public Health 2015 105 (5) e1-e6 OBJECTIVES: We assessed the burden of systemic lupus erythematosus (SLE) among Arab and Chaldean Americans residing in southeast Michigan. METHODS: For those meeting SLE criteria from the Michigan Lupus Epidemiology and Surveillance Registry, we determined Arab or Chaldean ethnicity by links with demographic data from birth certificates and with a database of Arab and Chaldean names. We compared prevalence and incidence of SLE for Arab and Chaldean Americans with estimates for non-Arab and non-Chaldean American Whites and Blacks. RESULTS: We classified 54 individuals with SLE as Arab and Chaldean Americans. The age-adjusted incidence and prevalence estimates for Arab and Chaldean Americans were 7.6 and 62.6 per 100 000, respectively. Arab and Chaldean Americans had a 2.1-fold excess SLE incidence compared with non-Arab and non-Chaldean American Whites. Arab and Chaldean American women had both significantly higher incidence rates (5.0-fold increase) and prevalence estimates (7.4-fold increase) than did Arab and Chaldean American men. CONCLUSIONS: Recognizing that Arab and Chaldean Americans experience different disease burdens from Whites is a first step toward earlier diagnosis and designing targeted interventions. Better methods of assigning ethnicity would improve research in this population. |
Assessment of training and technical assistance needs of Colorectal Cancer Control Program grantees in the U.S
Escoffery C , Hannon P , Maxwell AE , Vu T , Leeman J , Dwyer A , Mason C , Sowles S , Rice K , Gressard L . BMC Public Health 2015 15 (1) 49 BACKGROUND: Practitioners often require training and technical assistance to build their capacity to select, adapt, and implement evidence-based interventions (EBIs). The CDC Colorectal Cancer Control Program (CRCCP) aims to promote CRC screening to increase population-level screening. This study identified the training and technical assistance (TA) needs and preferences for training related to the implementation of EBIs among CRCCP grantees. METHODS: Twenty-nine CRCCP grantees completed an online survey about their screening activities, training and technical assistance in 2012. They rated desire for training on various evidence-based strategies to increase cancer screening, evidence-based competencies, and program management topics. They also reported preferences for training formats and facilitators and barriers to trainings. RESULTS: Many CRCCP grantees expressed the need for training with regards to specific EBIs, especially system-level and provider-directed EBIs to promote CRC screening. Grantees rated these EBIs as more difficult to implement than client-oriented EBIs. Grantees also reported a moderate need for training regarding finding EBIs, assessing organizational capacity, implementing selected EBIs, and conducting process and outcome evaluations. Other desired training topics reported with higher frequency were partnership development and data collection/evaluation. Grantees preferred training formats that were interactive such as on-site trainings, webinars or expert consultants. CONCLUSIONS: Public health organizations need greater supports for adopting evidence-based interventions, working with organizational-level change, partnership development and data management. Future capacity building efforts for the adoption of EBIs should focus on systems or provider level interventions and key processes for health promotion and should be delivered in a variety of ways to assist local organizations in cancer prevention and control. |
Attitudes toward management of sickle cell disease and its complications: a national survey of Academic Family Physicians
Mainous AG 3rd , Tanner RJ , Harle CA , Baker R , Shokar NK , Hulihan MM . Anemia 2015 2015 853835 OBJECTIVE: Sickle cell disease (SCD) is a disease that requires a significant degree of medical intervention, and family physicians are one potential provider of care for patients who do not have access to specialists. The extent to which family physicians are comfortable with the treatment of and concerned about potential complications of SCD among their patients is unclear. Our purpose was to examine family physician's attitudes toward SCD management. METHODS: Data was collected as part of the Council of Academic Family Medicine Educational Research Alliance (CERA) survey in the United States and Canada that targeted family physicians who were members of CERA-affiliated organizations. We examined attitudes regarding management of SCD. RESULTS: Overall, 20.4% of respondents felt comfortable with treatment of SCD. There were significant differences in comfort level for treatment of SCD patients depending on whether or not physicians had patients who had SCD, as well as physicians who had more than 10% African American patients. Physicians also felt that clinical decision support (CDS) tools would be useful for treatment (69.4%) and avoiding complications (72.6%) in managing SCD patients. CONCLUSIONS: Family physicians are generally uncomfortable with managing SCD patients and recognize the utility of CDS tools in managing patients. |
Celebrity appeal: reaching women to promote colorectal cancer screening
Cooper CP , Gelb CA , Lobb K . J Womens Health (Larchmt) 2015 24 (3) 169-73 The Centers for Disease Control and Prevention's Screen for Life: National Colorectal Cancer Action Campaign works with the Entertainment Industry Foundation's National Colorectal Cancer Research Alliance to develop public service announcements (PSAs) featuring celebrities. Selection of Screen for Life celebrity spokespersons is based on a variety of factors, including their general appeal and personal connection to colorectal cancer. Screen for Life PSAs featuring celebrities have been disseminated exclusively through donated media placements and have been formatted for television, radio, print, and out-of-home displays such as dioramas in airports, other transit stations, and shopping malls. A 2012 national survey with women aged 50-75 years (n=772) investigated reported exposure to Screen for Life PSAs featuring actor Terrence Howard. In total, 8.3% of women recalled exposure to the PSAs. Celebrity spokespersons can attract the attention of both target audiences and media gatekeepers who decide which PSAs will receive donated placements. |
Cervical cancer screening of underserved women in the United States: results from the National Breast and Cervical Cancer Early Detection Program, 1997-2012
Tangka FK , Howard DH , Royalty J , Dalzell LP , Miller J , O'Hara BJ , Sabatino SA , Joseph K , Kenney K , Guy GP Jr , Hall IJ . Cancer Causes Control 2015 26 (5) 671-86 OBJECTIVE: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides breast and cervical cancer screens to low-income, uninsured, and underinsured women. We describe the number and proportion of women eligible for cervical cancer screening services and the proportion of eligible women screened over the period 1997-2012. METHODS: Low-income, uninsured, and underinsured women aged 18-64 years who have not had a hysterectomy are eligible for cervical cancer screening through the NBCCEDP. We estimated the number of low-income, uninsured women using data from the US Census Bureau. We adjusted our estimates for hysterectomy status using the National Health Interview Survey and the Behavioral Risk Factor Surveillance System. We used data from the NBCCEDP to describe the number of women receiving NBCCEDP-funded screening and calculated the proportion of eligible women who received screening through the NBCCEDP at the national level (by age group, race/ethnicity) and at the state level by age group. We used the Medical Expenditure Panel Survey to estimate the proportion of NBCCEDP-eligible women who were screened outside the NBCCEDP and the proportion that are not screened. RESULTS: We estimate that in 2010-2012, 705,970 women aged 18-64 years, 6.5 % (705,970 of 9.8 million) of the eligible population, received NBCCEDP-funded Pap tests. We estimate that 60.2 % of eligible women aged 18-64 years were screened outside the NBCCEDP and 33.3 % were not screened. The NBCCEDP provided 623,603 screens to women aged 40-64 years, an estimated 16.5 % of the eligible population, and 83,660 screens to women aged 18-39 years, representing an estimated 1.2 % of the eligible population. The estimated proportions of eligible women screened in each state ranged from 1.5 to 32.7 % and 5 % to 73.2 % among the 18-64 and 40-64 years age groups, respectively. Changes in the proportion of eligible women screened over the study period were nonsignificant. CONCLUSIONS: Although the program provided cervical screening to over 700,000 women between 2010 and 2012, it served a small percent of those eligible. The proportion of women screened varied substantially across age groups, racial/ethnic groups, and states. Many low-income, uninsured women are not being screened. |
Molecular characterization of respiratory syncytial viruses infecting children reported to have received palivizumab immunoprophylaxis.
Oliveira DB , Iwane MK , Prill MM , Weinberg GA , Williams JV , Griffin MR , Szilagyi PG , Edwards KM , Staat MA , Hall CB , Durigon EL , Erdman DD . J Clin Virol 2015 65 26-31 BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of respiratory infections in children. Palivizumab (PZ) is the only RSV-specific immunoprophylaxis approved by the U.S. Food and Drug Administration. Mutations leading to amino acid substitutions in the PZ binding site of the RSV F protein have been associated with breakthrough RSV infections in patients receiving PZ. OBJECTIVE: To detect PZ resistance conferring mutations in RSV strains from children who received PZ. STUDY DESIGN: Children aged ≤24 months on October 31 who were hospitalized or had outpatient visits for respiratory illness and/or fever during October-May 2001-2008 in 3 US counties were included. PZ receipt was obtained from parent interviews and medical records among children subsequently infected with RSV. Archived nasal/throat swab specimens were tested for RSV by real-time RT-PCR. The coding region of the PZ binding site of the RSV F protein was sequenced using both Sanger and pyrosequencing methods. RESULTS: Of 8762 enrolled children, 375 (4.3%) were tested for RSV and had a history of PZ receipt, of which 56 (14.9%) were RSV-positive and 45 of these had available archived specimens. Molecular typing identified 42 partial F gene sequences in specimens from 39 children: 19 single RSV subgroup A, 17 subgroup B and 3 mixed infections. Nucleotide substitutions were identified in 12/42 (28.6%) RSV strains. PZ resistance mutations were identified in 4 (10.2%) of the 39 children, of which one had documented PZ receipt. CONCLUSIONS: Although RSV PZ resistance mutations were infrequent, most RSV-associated illnesses in children with a history of PZ receipt were not due to strain resistance. |
Retention and risk factors for loss to follow-up of female and male sex workers on antiretroviral treatment in Ivory Coast: a retrospective cohort analysis
Vuylsteke B , Semde G , Auld AF , Sabatier J , Kouakou J , Ettiegne-Traore V , Buve A , Laga M . J Acquir Immune Defic Syndr 2015 68 Suppl 2 S99-s106 BACKGROUND: Antiretroviral therapy (ART) for HIV-infected sex workers is an important HIV prevention strategy. However, sex workers may have additional challenges for retention in ART care. The objectives of this study were to assess retention of sex workers on ART in a routine setting in Ivory Coast and identify risk factors for loss to follow-up (LTFU). METHODS: The design was a retrospective cohort study. An analysis of clinic files was conducted in 2 sites providing ART services to sex workers in Ivory Coast. Demographic, behavior, and clinical data of female and male sex workers on ART were abstracted onto a standardized anonymous data collection form. Data collection took place between May 11 and 28, 2010. RESULTS: A total of 376 female and 38 male sex workers were included in the analysis. The retention probability was 75% at 6 months, 68% at 12 months, 55% at 24 months, and 47% at 36 months. Attrition was mainly because of LTFU. Factors significantly associated with LTFU in bivariate analysis were lower schooling level, later calendar year of starting ART, and not receiving initial adherence counseling. Later year of starting ART and not receiving adherence counseling at ART initiation remained significantly associated with LTFU in a multivariate Cox regression model. CONCLUSIONS: To improve the retention of sex workers on ART, there is a need for more in-depth investigation of the role of pre-ART counseling and the increasing rates of LTFU with each calendar year. |
Short communication: the Veterans Aging Cohort Study Index is an effective tool to assess baseline frailty status in a contemporary cohort of HIV-infected persons
Escota GV , Patel P , Brooks JT , Bush T , Conley L , Baker J , Kojic EM , Hammer J , Onen NF . AIDS Res Hum Retroviruses 2015 31 (3) 313-7 The Veterans Aging Cohort Study (VACS) Index has previously been used to identify frail HIV-infected persons. However, data demonstrating the independent association between the VACS Index and baseline frailty status is lacking. Furthermore, the ability of the VACS Index to also reflect transitions in frailty status over time is unknown. We used data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study) to determine independent association of baseline frailty status with the VACS Index. We also evaluated VACS Index changes with frailty status transitions over time. We included 303 participants (median age 48 years, 76% men, 57% non-Hispanic white, 91% with plasma HIV RNA <400 copies/ml, and median CD4(+) cell count 595 cells/ml) with baseline and follow-up frailty assessments and used the Fried's criteria to define frailty status. There were 184 (61%) nonfrail, 112 (37%) prefrail, and seven (2%) frail participants at baseline. Prefrail/frail participants had significantly higher median VACS Index scores compared with nonfrail participants (18 versus 10, p<0.001). In multivariable analysis, prefrailty/frailty was independently associated with a higher VACS Index score (odds ratio 1.025, p=0.019). After a median follow-up of 12 months, participants who remained prefrail/frail compared to those who remained nonfrail continued to have higher median VACS Index scores. The VACS Index score did not significantly change with transitions in frailty status over time. Our study highlights the potential utility of the VACS Index in frailty assessment within the clinical setting. |
A systematic review of the effects of visual inspection with acetic acid, cryotherapy, and loop electrosurgical excision procedures for cervical dysplasia in HIV-infected women in low- and middle-income countries
Forhan SE , Godfrey CC , Watts DH , Langley CL . J Acquir Immune Defic Syndr 2015 68 Suppl 3 S350-6 BACKGROUND: Cervical cancer, almost all of which is caused by human papillomavirus, accounts for 12% of female cancers worldwide and is more common among HIV-infected women. Nine of 10 deaths from cervical cancer occur in low- and middle-income countries (LMICs). Simple screening methods and outpatient treatment of precursor lesions save lives but the benefit of these interventions among HIV-infected women is uncertain. OBJECTIVE: We reviewed evidence of the effects of screening with visual inspection with acetic acid (VIA), and outpatient treatment for cervical precancer among HIV-infected women in LMIC. METHODS: A systematic review of articles published from January 1995 through July 2013 was conducted using key terms for VIA cervical screening, cervical precancer treatment with cryotherapy or loop electrosurgical excision procedure, HIV-infected women, low-resource settings, and outcomes, including morbidity and mortality. RESULTS: Of 2159 articles screened, 14 met inclusion criteria; all considered only morbidity outcomes. No articles dealt with the long-term impact of screening/treatment on cervical cancer incidence or mortality among HIV-infected women. Articles reported on performance of VIA, prevalence of cervical dysplasia, and complications and rates of recurrent dysplasia after treatment. CONCLUSIONS: Dysplasia prevalence and recurrence were higher among HIV-infected compared with HIV-uninfected women but morbidity from treatment was similar. Few data exist on long-term outcomes of VIA, cryotherapy, or loop electrosurgical excision procedure interventions among HIV-infected women in LMIC; longer-term outcomes research is needed to assess the effects of VIA or other screening modalities and outpatient treatment on prevention of cervical cancer among HIV-infected women. |
TB screening among people living with HIV/AIDS in resource-limited settings
Date A , Modi S . J Acquir Immune Defic Syndr 2015 68 Suppl 3 S270-3 Tuberculosis (TB) continues to be the leading cause of morbidity and mortality among people living with HIV (PLHIV), making improved prevention and treatment of HIV-associated TB critical to ensuring long-term survival of PLHIV. TB screening among PLHIV is central to implementation of the World Health Organization's 3 I's interventions for reducing the impact of the TB and HIV syndemics. Effective TB screening will result in the identification of PLHIV with presumptive TB disease (ie, those with a positive symptom screen who require appropriate evaluation, including the use of diagnostic tools such as the Xpert MTB/RIF assay) and those eligible for isoniazid preventive therapy (ie, those who have a negative clinical symptom screen or who have a positive screen but are found not to have TB disease). Identification of PLHIV with presumptive TB also facilitates implementation of basic administrative measures for TB infection control, including fast tracking of coughing patients and separation from noncoughing PLHIV to reduce TB transmission. By contributing to the early diagnosis of TB disease among PLHIV, TB screening is also critical to facilitate early initiation of antiretroviral treatment among PLHIV diagnosed with TB disease who might not otherwise be eligible for antiretroviral treatment based on CD4 count or clinical staging. TB screening thus serves as a gateway for multiple TB/HIV interventions and is an integral part of routine clinical services for PLHIV at each clinic visit. |
Time above 1500 copies: a viral load measure for assessing transmission risk of HIV-positive patients in care
Marks G , Gardner LI , Rose CE , Zinski A , Moore RD , Holman S , Rodriguez AE , Sullivan M , Giordano TP . AIDS 2015 29 (8) 947-54 OBJECTIVE: We examined HIV transmission potential of patients in care by analyzing the amount of person-time spent above a viral load threshold that increases risk for transmission. DESIGN: Observational cohort and supplemental data. METHODS: The cohort included HIV patients who received care at six HIV clinics in the United States, from 1 April 2009 to 31 March 2013, and had two or more viral load tests during this interval. Person-time (in days) above a viral load of 1500 copies/ml out of the total observation time was determined by inspecting consecutive pairs of viral load results and the time intervals between those pairs. The person-time rate ratios comparing demographic and clinical subgroups were estimated with Poisson regression. RESULTS: The cohort included 14 532 patients observed for a median of 1073 days with a median of 9 viral load records. Ninety per cent of the patients had been prescribed antiretroviral therapy. On average, viral load exceeded 1500 copies/ml during 23% of the patients' observation time (average of 84 days per year, per patient). Percentage of person-time above the threshold was higher among patients who had more than a fourth of their viral load pairs exceeding a 6-month interval (34% of observation time), patients not on antiretroviral therapy (58% of time), new/re-engaging patients (34% of time), patients 16-39 years of age (32% of time), and patients of black race (26% of time). CONCLUSION: HIV patients in care spent an average of nearly a quarter of their time with viral loads above 1500 copies/ml, higher among some subgroups, placing them at risk for potentially transmitting HIV to others. |
Tuberculosis trends - United States, 2014
Scott C , Kirking HL , Jeffries C , Price SF , Pratt R . MMWR Morb Mortal Wkly Rep 2015 64 (10) 265-9 In 2014, a total of 9,412 new tuberculosis (TB) cases were reported in the United States, with an incidence rate of 3.0* cases per 100,000 persons, a decrease of 2.2% from 2013. Although overall numbers of TB cases and rates continue to decline, the percentage decrease in rate is the smallest decrease in over a decade. This report summarizes provisional TB surveillance data reported to CDC's National Tuberculosis Surveillance System for 2014. TB cases and rates decreased among U.S.-born persons, and although the case rate also decreased among foreign-born persons,dagger there was an increase in total number of cases among foreign-born persons. The rate among foreign-born persons in the United States in 2014 was 13.4 times higher than among U.S.-born persons. Racial/ethnic minorities continue to be disproportionately affected by TB within the United States. Asians continue to be the racial/ethnic group with the largest number of TB cases. Compared with non-Hispanic whites, the TB rate among Asians was 28.5 times higher, whereas rates among non-Hispanic blacks and Hispanics were each eight times higher. Four states (California, Texas, New York, and Florida), representing approximately one third of the U.S. population, accounted for half of all TB cases reported in 2014. Continued progress toward TB elimination in the United States will require focused TB control efforts among populations and in geographic areas with disproportionate burdens of TB. |
Use of isoniazid preventive therapy for tuberculosis prophylaxis among people living with HIV/AIDS: a review of the literature
Briggs MA , Emerson C , Modi S , Taylor NK , Date A . J Acquir Immune Defic Syndr 2015 68 Suppl 3 S297-305 BACKGROUND: Tuberculosis (TB) is the leading preventable cause of death in persons living with HIV (PLHIV), accounting for over a quarter of all HIV-associated deaths in 2012. Isoniazid preventive therapy (IPT) has the potential to decrease TB-related cases and deaths in PLHIV; however, implementation of this has been slow in many high HIV- and TB-burden settings. METHODOLOGY: We performed an assessment of the evidence for the use of IPT in adults living with HIV based on a review of the literature published from 1995 to 2013. Eligible articles included data on mortality, morbidity, or retention in care related to the provision of IPT to adults with HIV in low- or middle-income countries. Cost-effectiveness information was also abstracted. RESULTS: We identified 41 articles involving over 45,000 PLHIV. While there was little evidence to demonstrate that IPT reduced mortality in PLHIV, there was substantial evidence that IPT reduced TB incidence. While these findings were consistent irrespective of CD4 or antiretroviral therapy status, studies frequently demonstrated a greater benefit among patients with a positive TB skin test (TST). Duration of effectiveness and benefits of prolonged therapy varied across settings. CONCLUSIONS: This analysis supports World Health Organization recommendations for the provision of IPT to PLHIV to reduce TB-associated morbidity and serves to highlight the need to strengthen IPT implementation. While there appears to be a greater benefit of IPT among PLHIV who are TST positive, IPT should be provided to all PLHIV without presumptive TB when TST is not available. |
Mortality amongst patients with influenza-associated severe acute respiratory illness, South Africa, 2009-2013
Cohen C , Moyes J , Tempia S , Groome M , Walaza S , Pretorius M , Dawood H , Chhagan M , Haffejee S , Variava E , Kahn K , von Gottberg A , Wolter N , Cohen AL , Malope-Kgokong B , Venter M , Madhi SA . PLoS One 2015 10 (3) e0118884 INTRODUCTION: Data on the burden and risk groups for influenza-associated mortality from Africa are limited. We aimed to estimate the incidence and risk-factors for in-hospital influenza-associated severe acute respiratory illness (SARI) deaths. METHODS: Hospitalised patients with SARI were enrolled prospectively in four provinces of South Africa from 2009-2013. Using polymerase chain reaction, respiratory samples were tested for ten respiratory viruses and blood for pneumococcal DNA. The incidence of influenza-associated SARI deaths was estimated at one urban hospital with a defined catchment population. RESULTS: We enrolled 1376 patients with influenza-associated SARI and 3% (41 of 1358 with available outcome data) died. In patients with available HIV-status, the case-fatality proportion (CFP) was higher in HIV-infected (5%, 22/419) than HIV-uninfected individuals (2%, 13/620; p = 0.006). CFPs varied by age group, and generally increased with increasing age amongst individuals >5 years (p<0.001). On multivariable analysis, factors associated with death were age-group 45-64 years (odds ratio (OR) 4.0, 95% confidence interval (CI) 1.01-16.3) and ≥65 years (OR 6.5, 95%CI 1.2-34.3) compared to 1-4 year age-group who had the lowest CFP, HIV-infection (OR 2.9, 95%CI 1.1-7.8), underlying medical conditions other than HIV (OR 2.9, 95%CI 1.2-7.3) and pneumococcal co-infection (OR 4.1, 95%CI 1.5-11.2). The estimated incidence of influenza-associated SARI deaths per 100,000 population was highest in children <1 year (20.1, 95%CI 12.1-31.3) and adults aged 45-64 years (10.4, 95%CI 8.4-12.9). Adjusting for age, the rate of death was 20-fold (95%CI 15.0-27.8) higher in HIV-infected individuals than HIV-uninfected individuals. CONCLUSION: Influenza causes substantial mortality in urban South Africa, particularly in infants aged <1 year and HIV-infected individuals. More widespread access to antiretroviral treatment and influenza vaccination may reduce this burden. |
Mortality hazard and survival after tuberculosis treatment
Miller TL , Wilson FA , Pang JW , Beavers S , Hoger S , Sharnprapai S , Pagaoa M , Katz DJ , Weis SE . Am J Public Health 2015 105 (5) e1-e8 OBJECTIVES: We compared mortality among tuberculosis (TB) survivors and a similar population. METHODS: We used local health authority records from 3 US sites to identify 3853 persons who completed adequate treatment of TB and 7282 individuals diagnosed with latent TB infection 1993 to 2002. We then retrospectively observed mortality after 6 to 16 years of observation. We ascertained vital status as of December 31, 2008, using the Centers for Disease Control and Prevention's National Death Index. We analyzed mortality rates, hazards, and associations using Cox regression. RESULTS: We traced 11 135 individuals over 119 772 person-years of observation. We found more all-cause deaths (20.7% vs 3.1%) among posttreatment TB patients than among the comparison group, an adjusted average excess of 7.6 deaths per 1000 person-years (8.8 vs 1.2; P < .001). Mortality among posttreatment TB patients varied with observable factors such as race, site of disease, HIV status, and birth country. CONCLUSIONS: Fully treated TB is still associated with substantial mortality risk. Cure as currently understood may be insufficient protection against TB-associated mortality in the years after treatment, and TB prevention may be a valuable opportunity to modify this risk. |
Pregnancy and severe influenza infection in the 2013-2014 influenza season
Louie JK , Salibay CJ , Kang M , Glenn-Finer RE , Murray EL , Jamieson DJ . Obstet Gynecol 2015 125 (1) 184-92 OBJECTIVE: To describe the epidemiologic and clinical characteristics of critically ill pregnant and postpartum women with influenza infection reported in the 2013-2014 season. METHODS: The California Department of Public Health conducts surveillance for patients with laboratory-confirmed influenza who die or require hospitalization in intensive care units. For this case series, we reviewed data on pregnant and postpartum (6 weeks or less from delivery) women reported in the 2013-2014 influenza season. RESULTS: From September 29, 2013, through May 17, 2014, 17 pregnant women with severe influenza were reported. The median age was 29 years (range 17-44 years). Sixteen (94%) were in the second or third trimester. Fifteen (88%) patients were hospitalized, nine (53%) required mechanical ventilation, five (29%) required emergent cesarean delivery, and four (24%) died. Of 14 patients with available information, only two (14%) received influenza vaccination during pregnancy. Seven patients who tested positive by polymerase chain reaction also had rapid influenza diagnostic testing performed; only one (14%) had a positive rapid influenza diagnostic test results. Fifteen patients received antiviral treatment; four (27%) began treatment within 48 hours of symptom onset. One additional patient was 36 days postpartum and required intensive care unit admission and mechanical ventilation for influenza-associated acute respiratory distress syndrome. CONCLUSION: Influenza remains a significant cause of morbidity and mortality in pregnant and postpartum women; in our series, a majority were not vaccinated. During the influenza season, pregnant women with suspected influenza should receive prompt empiric antiviral therapy, regardless of rapid influenza diagnostic test results or vaccination status. LEVEL OF EVIDENCE: III. |
Prevalence of HIV and hepatitis B virus co-infection in sub-Saharan Africa and the potential impact and program feasibility of hepatitis B surface antigen screening in resource-limited settings
Stabinski L , O'Connor S , Barnhart M , Kahn RJ , Hamm TE . J Acquir Immune Defic Syndr 2015 68 Suppl 3 S274-85 BACKGROUND: Screening people living with HIV for hepatitis B virus (HBV) co-infection is recommended in resource-rich settings to optimize HIV antiretroviral therapy (ART) and mitigate HBV-related liver disease. This review examines the need, feasibility, and impact of screening for HBV in resource-limited settings (RLS). METHODS: We searched 6 databases to identify peer-reviewed publications between 2007 and 2013 addressing (1) HIV/HBV co-infection frequency in sub-Saharan Africa (SSA); (2) performance of hepatitis B surface antigen (HBsAg) rapid strip assays (RSAs) in RLS; (3) impact of HBV co-infection on morbidity, mortality, or liver disease progression; and/or (4) impact of HBV-suppressive antiretroviral medications as part of ART on at least one of 5 outcomes (mortality, morbidity, HIV transmission, retention in HIV care, or quality of life). We rated the quality of individual articles and summarized the body of evidence and expected impact of each intervention per outcome addressed. RESULTS: Of 3940 identified studies, 85 were included in the review: 55 addressed HIV/HBV co-infection frequency; 6 described HBsAg RSA performance; and 24 addressed the impact of HIV/HBV co-infection and ART. HIV/HBV frequency in sub-Saharan Africa varied from 0% to >28.4%. RSA performance in RLS showed good, although variable, sensitivity and specificity. Quality of studies ranged from strong to weak. Overall quality of evidence for the impact of HIV/HBV co-infection and ART on morbidity and mortality was fair and good to fair, respectively. CONCLUSIONS: Combined, the body of evidence reviewed suggests that HBsAg screening among people living with HIV could have substantial impact on preventing morbidity and mortality among HIV/HBV co-infected individuals in RLS. |
Prevalence of tuberculosis in adolescents, western Kenya; implications for control programs
Nduba V , Hoog AH , Mitchell E , Onyango P , Laserson K , Borgdorff M . Int J Infect Dis 2015 35 11-7 OBJECTIVE: The aim was to determine the prevalence of tuberculosis in adolescents in Western Kenya. METHODS: We conducted a cohort study of 5004 adolescents aged 12-18 years. Adolescents were screened for prevalent tuberculosis using clinical criteria, history of TB contact, and a mantoux test. TB suspects were investigated through 2 sputum examinations (microscopy and liquid culture), and chest radiography. RESULTS: Out of 5004 adolescents enrolled, 1960 (39.2%) were identified as a TB suspect including 1544 with a positive mantoux (prevalence 1544/4808 32.1%), 515 having symptoms suggestive of TB (10.3%) and 144 (2.9%) with household TB contact. Sixteen culture-confirmed (definite) and 18 probable pulmonary TB (PTB) cases were identified reflecting a prevalence estimate of 3.2/1,000 (definite) and 6.8/1,000 all PTB respectively. Only one smear-positive case was detected. The case notification rate among 12-18 year old adolescents for all TB was 101/100,000 yielding a patient diagnostic rate of 0.13 (95% CI 0.03,3.7) cases detected per person-year for all TB. CONCLUSION: The prevalence of PTB among adolescents is high with the majority of cases not detected routinely. Innovative active case finding including wider use of Xpert MTB/RIF is needed, to detect smear-negative TB among adolescents. |
Prioritizing HIV care and support interventions - moving from evidence to policy
Langley CL , Lapidos-Salaiz I , Hamm TE , Bateganya MH , Firth J , Wilson M , Martin J , Dierberg K . J Acquir Immune Defic Syndr 2015 68 Suppl 3 S375-8 Over the past decade, tremendous progress has been made in addressing the HIV epidemic in low- and middle-income countries, with expanded access to antiretroviral therapy (ART) in many countries, and advances in key areas, such as prevention of mother-to-child transmission and voluntary medical male circumcision.1 However, many gaps remain, with limited coverage for care and treatment in many countries1 and ongoing challenges for epidemic control. As countries and donors work to expand access to critical HIV prevention, care and treatment services in an era of declining funding and multiple competing needs, programs will need to determine strategic priorities, identifying and implementing interventions that demonstrate the greatest impact on key outcomes. | The US President's Emergency Plan for AIDS Relief (PEPFAR), which supports HIV programs in 36 countries and regions in Africa, Asia, Eastern Europe, Central America, and the Caribbean, is currently engaged in such a process, re-examining overall priorities with the goal of controlling the epidemic and achieving an AIDS-free generation. As outlined in PEPFAR 3.0: Controlling the epidemic: Delivering on the promise of an AIDS-free generation,2 PEPFAR is in the process of realigning geographic and programmatic focus, emphasizing strategic investments to scale up effective evidence-based interventions in high HIV prevalence areas and populations to maximize impact on the epidemic. As part of this focus on impact, efficiency, and sustainability, PEPFAR is reassessing programmatic priorities both within and across program areas. PEPFAR-supported programs are engaged in a similar prioritization process at the country/regional level. |
Effects of oseltamivir treatment of index patients with influenza on secondary household illness in an urban setting in Bangladesh: secondary analysis of a randomised, placebo-controlled trial
Fry AM , Goswami D , Nahar K , Sharmin AT , Rahman M , Gubareva L , Trujillo A , Barnes J , Azim T , Bresee J , Luby SP , Brooks WA . Lancet Infect Dis 2015 15 (6) 654-62 BACKGROUND: Antiviral drugs are a proposed medical intervention to reduce household transmission of influenza viruses. In a previously described randomised, placebo-controlled trial in Dhaka, Bangladesh, we showed that oseltamivir treatment of index patients was able to reduce influenza symptom duration and virus shedding. In a further analysis that is part of the same study, we aimed to assess efficacy of oseltamivir to reduce secondary household illnesses in the same cohort. METHODS: In this double-blind oseltamivir efficacy trial, we identified index patients aged older than 1 year through surveillance of households in Dhaka, Bangladesh. We randomly allocated eligible patients (1:1) to receive oseltamivir or placebo twice-daily for 5 days, and we stratified them by enrolment 48 h versus 48-120 h since illness onset. Participants provided nasal wash specimens at enrolment and 2, 4, and 7 days after enrolment and were visited daily by a research assistant to record symptoms, both in index patients and in household members. For this part of the study, household members were asked to give respiratory specimens for influenza PCR testing. Our primary outcomes were household secondary illness and PCR-confirmed influenza virus infection, assessed in household members of all randomly allocated index patients. This trial is registered with ClinicalTrials.gov, number NCT00707941. FINDINGS: From May 11, 2008, to Dec 31, 2010, we enrolled 1190 index patients with 4694 household members. 592 patients were allocated to placebo (2292 household members) and 598 to oseltamivir (2402 household members). Household secondary illness was lower in the oseltamivir group (196 [8%] influenza cases) than in the placebo group (233 [10%]; odds ratio [OR] 0.77, 95% CI 0.60-0.98, p=0.031). PCR-confirmed influenza virus infection did not differ between the placebo (103 [5%]) and oseltamivir groups (92 [4%]; 0.84, 0.59-1.19, p=0.319); however, only 243 (57%) of ill household members gave a specimen for analysis. INTERPRETATION: In a crowded, low income setting, oseltamivir treatment of index patients resulted in a small reduction of secondary influenza in their households. Even this slight reduction, in the setting of widespread antiviral use during a community influenza outbreak, might result in reductions in overall disease burden. FUNDING: Centers for Disease Control and Prevention (in an agreement with the International Centre for Diarrhoeal Disease Research, Bangladesh). |
HIV infection and HIV-associated behaviors among persons who inject drugs - 20 cities, United States, 2012
Spiller MW , Broz D , Wejnert C , Nerlander L , Paz-Bailey G . MMWR Morb Mortal Wkly Rep 2015 64 (10) 270-5 In the United States, an estimated 7% of new diagnoses of human immunodeficiency virus (HIV) infection in 2012 were attributed to injection drug use, and an additional 3% to male-to-male sexual contact and injection drug use. To monitor HIV prevalence and behaviors associated with HIV risk and prevention among persons who inject drugs (PWID), CDC's National HIV Behavioral Surveillance (NHBS) system conducts interviews and HIV testing in selected cities. This report summarizes HIV prevalence and behaviors among PWID interviewed and tested in 20 cities in 2012. Of the 10,002 PWID tested, 11% had a positive HIV test result. Among 9,425 PWID included in the behavioral analysis, 30% receptively shared syringes, 70% had vaginal sex without a condom, 25% had heterosexual anal sex without a condom, and 5% of males had male-to-male sexual contact without a condom in the previous 12 months. Fifty-one percent of PWID included in the behavioral analysis had been tested for HIV, 25% participated in an HIV behavioral intervention, and 39% participated in substance abuse treatment in the previous 12 months. Additional efforts are needed to reduce risk behaviors and increase access to HIV testing, drug treatment, and other HIV prevention programs to further reduce HIV infections among PWID. |
HIV knowledge among a longitudinal cohort of juvenile detainees in an urban setting
Bcheraoui CE , Zhang X , Welty LJ , Abram KM , Teplin LA , Sutton MY . J Correct Health Care 2015 21 (2) 112-24 The authors investigated HIV knowledge change among a cohort of juvenile detainees. Participants completed an HIV knowledge survey at baseline and up to 4 more times over 6 years. The authors calculated knowledge scores; the time serial trend of scores was modeled using generalized estimating equations. A baseline survey was completed by 798 participants, ages 14 to 18 years; mean HIV knowledge scores ranged from 11.4 to 14.1 (maximum score = 18). Males had significantly lower HIV knowledge scores than females at baseline only. Over time, Hispanic participants had significantly lower scores than non-Hispanic Black and non-Hispanic White participants. Overall, HIV knowledge increased but was still suboptimal 5 years after baseline. These findings suggest the need to develop and strengthen HIV prevention education programs in youth detention settings. |
HIV stigma experienced by young men who have sex with men (MSM) living with HIV infection
Jeffries WL , Townsend ES , Gelaude DJ , Torrone EA , Gasiorowicz M , Bertolli J . AIDS Educ Prev 2015 27 (1) 58-71 Stigma can compromise the health of persons living with HIV. Although HIV is increasingly affecting young men who have sex with men (MSM), little is known about their experiences with HIV stigma. We used narrative data to examine HIV stigma experienced by young MSM living with HIV. Data came from 28 qualitative interviews with young MSM. We used inductive content analysis to identify themes across these interviews. Participants commonly discussed negative perceptions and treatment of persons living with HIV. Stigma could result in nondisclosure of HIV status, internalized stigma, and avoidance of HIV-related things. Some men discussed strategies that might combat stigma. Findings suggest that HIV stigma might challenge young MSM's health by undermining health-conducive resources (e.g., social support) and contributing to HIV vulnerability. Interventions that counteract HIV stigma may help to create environments that promote well-being among young MSM living with HIV. |
Human Ebola virus infection results in substantial immune activation
McElroy AK , Akondy RS , Davis CW , Ellebedy AH , Mehta AK , Kraft CS , Lyon GM , Ribner BS , Varkey J , Sidney J , Sette A , Campbell S , Stroher U , Damon I , Nichol ST , Spiropoulou CF , Ahmed R . Proc Natl Acad Sci U S A 2015 112 (15) 4719-24 Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus. |
Impact of cotrimoxazole and insecticide-treated nets for malaria prevention on key outcomes among HIV-infected adults in low- and middle-income countries: a systematic review
Saadani Hassani A , Marston BJ . J Acquir Immune Defic Syndr 2015 68 Suppl 3 S306-17 BACKGROUND: HIV-infected adults are at increased risk of severe malaria and death. Malaria prevention in people living with HIV (PLHIV) consists of several interventions, including cotrimoxazole (CTX) prophylaxis and insecticide-treated nets (ITNs). We conducted a systematic review of the available evidence. METHODS: MEDLINE, EmBase, Global Health, CINAHL, SOCA, and African Index Medicus were used to identify articles relevant to the CTX prophylaxis and ITNs interventions from 1995 to July 2014. For each individual study, we assessed the quality of evidence and the impact of the 2 interventions on the outcomes of mortality, morbidity, retention in care, quality of life, and/or prevention of ongoing HIV transmission. For each outcome, we summarized the quality of the overall body of evidence, the expected impact, and costing and cost-effectiveness (CE). FINDINGS: The overall quality of evidence regarding malaria-related morbidity was rated as "good" for CTX prophylaxis and "fair" for ITN use; the expected "impact" of these interventions on morbidity was rated "high" and "uncertain," respectively. Three studies that addressed the costing and CE of ITN provision for malaria prevention in PLHIV consisted of 2 full "level 1" and 1 partial "level 2" economic evaluations. CONCLUSIONS: CTX prophylaxis is effective in reducing malaria-related morbidity among PLHIV. Limited evidence is available with respect to the impact and the CE of ITN use and/or provision in this population. |
The impact of HIV care and support interventions on key outcomes in low- and middle-income countries: a literature review - introduction
Kaplan JE , Hamm TE , Forhan S , Saadani Hassani A , Bang G , Weyant E , Tchuenche M , Langley C , Lapidos-Salaiz I , Bateganya MH . J Acquir Immune Defic Syndr 2015 68 Suppl 3 S253-6 As of December 2012, an estimated 35.3 million persons were living with HIV; approximately two thirds of these people were living in sub-Saharan Africa.1 The response to the HIV pandemic in Africa and in other low-and middle-income regions of the world has consisted of a variety of bilateral and multi-lateral support from donor agencies, as well as local support from countries that have been able to afford it. A majority of the support has been directed towards HIV care and treatment. | Accordingly, the past ten years have witnessed a remarkable increase in the number of HIV-infected persons receiving antiretroviral therapy (ART) in low- and middle-income countries--from 300,000 in 2003 to 9.7 million in 20121,2. Expanded access to ART in these countries has led to significant proportions of eligible persons enrolled on ART, reaching coverage rates as high as 61% based on the World Health Organization (WHO) treatment guidelines eligibility criteria of CD4 <350 cells/uL) in 2012.1 In 2013, WHO revised its guidelines to indicate eligibility at CD4 <500 cells/uL; under these criteria, only 34% of eligible persons were on ART in 2013.1 Nevertheless, these changes in access to ART were estimated to have averted 4.2 million deaths through 20122.1 | HIV treatment programs in low- and middle-income countries have been supported by a variety of sources, including over $50 billion through the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) from 2004 to 20133. PEPFAR programs are coordinated by the U.S. Department of State’s Office of the U.S. Global AIDS Coordinator (OGAC) in Washington, D.C.,; oversight of in-country expenditures is supported by additional U.S. government(USG) agencies with the majority of funds concentrated in 36 countries and regions 4 in sub-Saharan Africa, South and Central Asia, Eastern Europe, Central America and the Caribbean. PEPFAR supports a range of HIV care and treatment services besides ART including clinical (e.g. monitoring to determine eligibility for ART and prevention and treatment of opportunistic infections) and non-clinical services (e.g. psychological, social, and preventive)4. Services implemented through PEPFAR support in each country are determined through a dialogue between the USG, and host governments. PEPFAR country operating plans and budgets are submitted annually and reviewed by USG staff. |
The impact of social services interventions in developing countries: a review of the evidence of impact on clinical outcomes in people living with HIV
Bateganya MH , Dong M , Oguntomilade J , Suraratdecha C . J Acquir Immune Defic Syndr 2015 68 Suppl 3 S357-67 BACKGROUND: Social service interventions have been implemented in many countries to help people living with HIV (PLHIV) and household members cope with economic burden as a result of reduced earning or increased spending on health care. However, the evidence for specific interventions-economic strengthening and legal services-on key health outcomes has not been appraised. METHODS: We searched electronic databases from January 1995 to May 2014 and reviewed relevant literature from resource-limited settings on the impact of social service interventions on mortality, morbidity, retention in HIV care, quality of life, and ongoing HIV transmission and their cost-effectiveness. RESULTS: Of 1685 citations, 8 articles reported the health impact of economic strengthening interventions among PLHIV in resource-limited settings. None reported on legal services. Six of the 8 studies were conducted in sub-Saharan Africa: 1 reported on all 5 outcomes and 2 reported on 4 and 2 outcomes, respectively. The remaining 5 reported on 1 outcome each. Seven studies reported on quality of life. Although all studies reported some association between economic strengthening interventions and HIV care outcomes, the quality of evidence was rated fair or poor because studies were of low research rigor (observational or qualitative), had small sample size, or had other limitations. The expected impact of economic strengthening interventions was rated as high for quality of life but uncertain for all the other outcomes. CONCLUSIONS: Implementation of economic strengthening interventions is expected to have a high impact on the quality of life for PLHIV but uncertain impact on mortality, morbidity, retention in care, and HIV transmission. More rigorous research is needed to explore the impact of more targeted intervention components on health outcomes. |
Impact of support groups for people living with HIV on clinical outcomes: a systematic review of the literature
Bateganya MH , Amanyeiwe U , Roxo U , Dong M . J Acquir Immune Defic Syndr 2015 68 Suppl 3 S368-74 BACKGROUND: Support groups for people living with HIV are integrated into HIV care and treatment programs as a modality for increasing patient literacy and as an intervention to address the psychosocial needs of patients. However, the impact of support groups on key health outcomes has not been fully determined. METHODS: We searched electronic databases from January 1995 through May 2014 and reviewed relevant literature on the impact of support groups on mortality, morbidity, retention in HIV care, quality of life (QOL), and ongoing HIV transmission, as well as their cost-effectiveness. RESULTS: Of 1809 citations identified, 20 met the inclusion criteria. One reported on mortality, 7 on morbidity, 5 on retention in care, 7 on QOL, and 7 on ongoing HIV transmission. Eighteen (90%) of the articles reported largely positive results on the impact of support group interventions on key outcomes. Support groups were associated with reduced mortality and morbidity, increased retention in care, and improved QOL. Because of study limitations, the overall quality of evidence was rated as fair for mortality, morbidity, retention in care, and QOL, and poor for HIV transmission. CONCLUSIONS: Implementing support groups as an intervention is expected to have a high impact on morbidity and retention in care and a moderate impact on mortality and QOL of people living with HIV. Support groups improve disclosure with potential prevention benefits but the impact on ongoing transmission is uncertain. It is unclear whether this intervention is cost-effective given the paucity of studies in this area. |
The impact of water, sanitation, and hygiene interventions on the health and well-being of people living with HIV: a systematic review
Yates T , Lantagne D , Mintz E , Quick R . J Acquir Immune Defic Syndr 2015 68 Suppl 3 S318-30 BACKGROUND: Access to improved water supply and sanitation is poor in low-income and middle-income countries. Persons living with HIV/AIDS (PLHIV) experience more severe diarrhea, hospitalizations, and deaths from diarrhea because of waterborne pathogens than immunocompetent populations, even when on antiretroviral therapy (ART). METHODS: We examined the existing literature on the impact of water, sanitation, and hygiene (WASH) interventions on PLHIV for these outcomes: (1) mortality, (2) morbidity, (3) retention in HIV care, (4) quality of life, and (5) prevention of ongoing HIV transmission. Cost-effectiveness was also assessed. Relevant abstracts and articles were gathered, reviewed, and prioritized by thematic outcomes of interest. Articles meeting inclusion criteria were summarized in a grid for comparison. RESULTS: We reviewed 3355 citations, evaluated 132 abstracts, and read 33 articles. The majority of the 16 included articles focused on morbidity, with less emphasis on mortality. Contaminated water, lack of sanitation, and poor hygienic practices in homes of PLHIV increase the risk of diarrhea, which can result in increased viral load, decreased CD4 counts, and reduced absorption of nutrients and antiretroviral medication. We found WASH programming, particularly water supply, household water treatment, and hygiene interventions, reduced morbidity. Data were inconclusive on mortality. Research gaps remain in retention in care, quality of life, and prevention of ongoing HIV transmission. Compared with the standard threshold of 3 times GDP per capita, WASH interventions were cost-effective, particularly when incorporated into complementary programs. CONCLUSIONS: Although research is required to address behavioral aspects, evidence supports that WASH programming is beneficial for PLHIV. |
Integrating prevention interventions for people living with HIV into care and treatment programs: a systematic review of the evidence
Medley A , Bachanas P , Grillo M , Hasen N , Amanyeiwe U . J Acquir Immune Defic Syndr 2015 68 Suppl 3 S286-96 INTRODUCTION: This review assesses the impact of prevention interventions for people living with HIV on HIV-related mortality, morbidity, retention in care, quality of life, and prevention of ongoing HIV transmission in resource-limited settings (RLSs). METHODS: We conducted a systematic review of studies reporting the results of prevention interventions for people living with HIV in RLS published between January 2000 and August 2014. Standardized methods of searching and data abstraction were used. RESULTS: Ninety-two studies met the eligibility criteria: 24 articles related to adherence counseling and support, 13 on risk reduction education and condom provision, 19 on partner HIV testing and counseling, 14 on provision of family planning services, and 22 on assessment and treatment of other sexually transmitted infections. Findings indicate good evidence that adherence counseling and sexually transmitted infection treatment can have a high impact on morbidity, whereas risk reduction education, partner HIV testing and counseling, and family planning counseling can prevent transmission of HIV. More limited evidence was found to support the impact of these interventions on retention in care and quality of life. Most studies did not report cost information, making it difficult to draw conclusions about the cost-effectiveness of these interventions. CONCLUSIONS: This evidence suggests that these prevention interventions, if brought to sufficient scale and coverage, can help support and optimize the impact of core treatment and prevention interventions in RLS. Further operational research with more rigorous study designs, and ideally with biomarkers and costing information, is needed to determine the best model for providing these interventions in RLS. |
Acceptability, feasibility and challenges of implementing an HIV prevention intervention for people living with HIV/AIDS among healthcare providers in Mozambique: results of a qualitative study
Jaiantilal P , Gutin SA , Cummings B , Mbofana F , Rose CD . SAHARA J 2015 12 (1) 2-9 Despite the Mozambique government's efforts to curb human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), national prevalence is 11.5% and support is needed to expand HIV-related services and improve program quality. Positive prevention (PP) programs, which prioritize HIV prevention with people living with HIV and AIDS (PLHIV), have been recognized as an important intervention for preventing new HIV infections. To address this, an evidence-based PP training intervention was implemented with HIV healthcare providers in Mozambique. This study focuses on the acceptability and feasibility of a PP intervention in HIV clinics from the healthcare provider perspective. In-depth interviews were conducted with 31 healthcare providers from three provinces who participated in PP trainings in Mozambique. Interview data were coded using content analysis. Study data suggest that healthcare providers found PP acceptable, feasible to implement in their HIV work in clinic settings, and valued this strategy to improve HIV prevention. The PP training also led providers to feel more comfortable counseling their patients about prevention, with a more holistic approach that included HIV testing, treatment and encouraging PLHIV to live positively. While overall acceptance of the PP training was positive, several barriers to feasibility surfaced in the data. Patient-level barriers included resistance to disclosing HIV status due to fear of stigma and discrimination, difficulty negotiating for condom use, difficulty engaging men in testing and treatment, and the effects of poverty on accessing care. Providers also identified work environment barriers including high patient load, time constraints, and frequent staff turnover. Recognizing PP as an important intervention, healthcare providers should be trained to provide comprehensive prevention, care and treatment for PLHIV. Further work is needed to explore the complex social dynamics and cultural challenges such as gender inequalities, stigma and discrimination which hinder the full impact of PP interventions in this context. |
Assessment of the impact of cotrimoxazole prophylaxis on key outcomes among HIV-infected adults in low- and middle-income countries: a systematic review
Saadani Hassani A , Marston BJ , Kaplan JE . J Acquir Immune Defic Syndr 2015 68 Suppl 3 S257-69 BACKGROUND: Cotrimoxazole (CTX) prophylaxis is among the key interventions provided to HIV-infected individuals in resource-limited settings. We conducted a systematic review of the available evidence. METHODS: MEDLINE, Embase, Global Health, CINAHL, SOCA, and African Index Medicus (AIM) were used to identify articles relevant to the CTX prophylaxis intervention from 1995 to 2014. Included articles addressed impact of CTX prophylaxis on the outcomes of mortality, morbidity, retention in care, quality of life, and/or prevention of ongoing HIV transmission. We rated the quality of evidence in individual articles and assessed the overall quality of the body of evidence, the expected impact, and the cost effectiveness (CE) for each outcome. RESULTS: Of the initial 1418 identified articles, 42 met all inclusion criteria. These included 9 randomized controlled trials, 26 observational studies, 2 systematic reviews with meta-analysis, 1 other systematic review, and 4 CE studies. The overall quality of evidence was rated as "good" and the expected impact "high" for both mortality and morbidity. The overall quality of evidence from the 4 studies addressing retention in care was rated as "poor," and the expected impact on retention was rated as "uncertain." The 4 assessed CE studies showed that provision of CTX prophylaxis is cost effective and sometimes cost saving. No studies addressed impact on quality of life or HIV transmission. CONCLUSIONS: CTX prophylaxis is a cost-effective intervention with expected high impact on morbidity and mortality reduction in HIV-infected adults in resource-limited settings. Benefits are seen in both pre-antiretroviral therapy and antiretroviral therapy populations. |
Comparison of rates of death having any death-certificate mention of heart, kidney, or liver disease among persons diagnosed with HIV infection with those in the general US population, 2009-2011
Whiteside YO , Selik R , An Q , Huang T , Karch D , Hernandez AL , Hall HI . Open AIDS J 2015 9 14-22 OBJECTIVE: Compare age-adjusted rates of death due to liver, kidney, and heart diseases during 2009-2011 among US residents diagnosed with HIV infection with those in the general population. METHODS: Numerators were numbers of records of multiple-cause mortality data from the national vital statistics system with an ICD-10 code for the disease of interest (any mention, not necessarily the underlying cause), divided into those 1) with and 2) without an additional code for HIV infection. Denominators were 1) estimates of persons living with diagnosed HIV infection from national HIV surveillance system data and 2) general population estimates from the US Census Bureau. We compared age-adjusted rates overall (unstratified by sex, race/ethnicity, or region of residence) and stratified by demographic group. RESULTS: Overall, compared with the general population, persons diagnosed with HIV infection had higher age-adjusted rates of death reported with hepatitis B (rate ratio [RR]=42.6; 95% CI: 34.7-50.7), hepatitis C (RR=19.4; 95% CI: 18.1-20.8), liver disease excluding hepatitis B or C (RR=2.1; 95% CI: 1.8-2.3), kidney disease (RR=2.4; 95% CI: 2.2-2.6), and cardiomyopathy (RR=1.9; 95% CI: 1.6-2.3), but lower rates of death reported with ischemic heart disease (RR=0.6; 95% CI: 0.6-0.7) and heart failure (RR=0.8; 95% CI: 0.6-0.9). However, the differences in rates of death reported with the heart diseases were insignificant in some demographic groups. CONCLUSION: Persons with HIV infection have a higher risk of death with liver and kidney diseases reported as causes than the general population. |
Correlates of HIV infection among female sex workers in Vietnam: injection drug use remains a key risk factor
Le LV , Nguyen TA , Tran HV , Gupta N , Duong TC , Tran HT , Nadol P , Sabin K , Maher L , Kaldor JM . Drug Alcohol Depend 2015 150 46-53 OBJECTIVE: Women who sell sex and use drugs have dual risks for HIV infection. Despite increasing reports of drug use among female sex workers (FSW) in Vietnam, FSW HIV interventions remain focused mainly on sexual risk reduction. We assessed the impact of drug use and inconsistent condom use on HIV infection among FSW in Vietnam, which few studies have quantified. METHODS: We surveyed 5298 women aged ≥18 years who had sold sex in the past month from ten geographically dispersed provinces. We performed multivariate logistic regression on data from provinces with high (≥10%) or low (<10%) HIV prevalence among FSW. RESULTS: Compared to FSW who never used illicit drugs, the odds of HIV infection among FSW who had ever injected drugs and those who reported non-injection drug use were 3.44 (CI 2.32-5.09) and 1.76 (CI 1.14-2.71), respectively, in high-prevalence provinces. FSW who always used condoms with clients had lower odds of HIV infection than those who did not (AOR=0.71; CI 0.52-0.98). In low-prevalence provinces lifetime injection drug use (AOR 22.05, CI 12.00-40.49), but not non-injecting drug use or inconsistent condom use, was significantly associated with HIV infection. CONCLUSIONS: Because injection drug use and inconsistent condom use were key risk factors for HIV infection in high-prevalence provinces, drug injection risk reduction should be as much a focus of HIV prevention as sexual risk reduction. Where HIV prevalence remains low in FSW, a more general emphasis on harm reduction for all drug users will benefit FSW. |
Cryptococcal antigen screening and early antifungal treatment to prevent cryptococcal meningitis: a review of the literature
Kaplan JE , Vallabhaneni S , Smith RM , Chideya-Chihota S , Chehab J , Park B . J Acquir Immune Defic Syndr 2015 68 Suppl 3 S331-9 BACKGROUND: Screening individuals with AIDS for serum cryptococcal antigen (CrAg), followed by treatment of CrAg positives with antifungals, may prevent cryptococcal meningitis. This review examined data on CrAg screening and treatment in resource-limited settings. METHODS: We searched articles published during 2007-2014 on the effectiveness and cost-effectiveness of CrAg screening and treatment on the outcomes of mortality, morbidity, retention in care, quality of life, and/or prevention of ongoing HIV transmission. We rated overall quality of individual articles, summarized the body of evidence, the expected impact, and cost-effectiveness for each outcome. RESULTS: We identified 2613 articles. Eight met all inclusion criteria. Five studies addressed mortality and/or morbidity outcomes; all were observational and had small sample sizes; 3 lacked a comparison group. Ratings of study quality ranged from "medium" to "weak," and the quality of the overall body of evidence for mortality and morbidity outcomes was rated as "fair." The intervention's expected impact on mortality and morbidity was rated as "moderate." The 4 cost-effectiveness studies included in the analysis showed that CrAg screening and treatment interventions are highly cost-effective. No studies addressed retention in care, quality of life, or HIV transmission. CONCLUSIONS: Although limited, the body of evidence regarding CrAg screening and treatment suggests that the intervention may have an impact on preventing cryptococcal meningitis and death in persons with AIDS. Additional research is needed to quantify the intervention's effectiveness and identify optimal treatment dosing and implementation best practices. |
Hospitalizations associated with influenza and respiratory syncytial virus among patients attending a network of private hospitals in South Africa, 2007-2012
Kyeyagalire R , Tempia S , Cohen AL , Smith AD , McAnerney JM , Dermaux-Msimang V , Cohen C . BMC Infect Dis 2014 14 (1) 694 BACKGROUND: Influenza and respiratory syncytial virus (RSV) infection are common causes of lower respiratory tract illness. Data on their burden in low and middle-income settings and from Africa are scarce. We aimed to estimate age-specific rates of hospitalization attributable to influenza and RSV among patients attending private hospitals in South Africa during 2007-2012. METHODS: We estimated annual age-specific rates of influenza- and RSV-associated hospitalization (that is respiratory hospitalizations likely due to influenza or RSV infection) by applying regression models to monthly administrative hospitalization data from a national private hospital group, using influenza and RSV surveillance data as covariates. RESULTS: Estimated mean hospitalization rates associated with seasonal influenza were 75 (95% confidence interval (CI), 41-108) and 3 (95% CI, 2-5) per 100,000 person-years for all-respiratory and all-circulatory causes, respectively. Children <1 year and adults ≥ 75 years were the most affected, with influenza-associated all-respiratory hospitalization rates estimated at 255 (95% CI, 143-358) and 380 (95% CI, 227-506) per 100,000 person-years, respectively. Excess all-circulatory hospitalizations associated with seasonal influenza were only observed in adults ≥ 65 years. Annual hospitalization rates associated with RSV averaged an estimate of 223 (95% CI, 128-317) per 100,000 person-years for all-respiratory causes. Among children <1 year, RSV-associated all-respiratory hospitalization rate of 7,601 (95% CI, 4,312-10,817) per 100,000 person-years was estimated. CONCLUSIONS: Influenza and RSV substantially contributed to hospitalizations over the study period. |
Neglected tropical disease control and elimination: is human displacement an achilles heel?
Errecaborde KM , Stauffer W , Cetron M . PLoS Negl Trop Dis 2015 9 (3) e0003535 The United Nations High Commission for Refugees (UNHCR) has estimated that over 40 million people [1] are currently displaced and have variable access to health care in the country in which they reside. Populations displaced by conflict are largely disenfranchised, and high prevalence of neglected tropical diseases (NTDs) has been documented [2]. NTDs generally affect the least advantaged people in poor societies—populations with little voice or representation. These already susceptible people become even more vulnerable when forced from their communities as internally displaced persons (IDPs), refugees, or forced migrants. To further complicate matters, many of these people of concern are under 18 years old. Children experience the greatest risk and suffer the most consequences of NTDs. As marginalized populations flee from conflict or environmental catastrophe, they are often burdened with insidious NTDs ranging from asymptomatic to overt and debilitating disease. Many suffer from chronic consequences such as malnutrition, growth stunting and developmental delays, inhibiting chances for sustainable livelihoods and making it less likely that they will successfully overcome the adversity of displacement. | The World Health Organization (WHO) has defined 17 key neglected diseases, but several others exist [3]. These diseases are highlighted in Millennium Development Goal (MDG) 6, which aims to combat HIV/AIDS and “other diseases,” of which the NTDs are discussed at length [4,5]. It is the intent of these authors to raise the awareness of readers, and argue that inclusion of these displaced populations in preventive chemotherapy (PCT) programs and multi-model community-based interventions is not only necessary for sustained success of NTD control but is also a moral imperative. |
Prescription practices involving opioid analgesics among Americans with Medicaid, 2010
Mack KA , Zhang K , Paulozzi L , Jones C . J Health Care Poor Underserved 2015 26 (1) 182-98 Recent state-based studies have shown an increased risk of opioid overdose death in Medicaid populations. To explore one side of risk, this study examines indicators of potential opioid inappropriate use or prescribing among Medicaid enrollees. We examined claims from enrollees aged 18-64 years in the 2010 Truven Health MarketScan(R) Multi-State Medicaid database, which consisted of weighted and nationally representative data from 12 states. Pharmaceutical claims were used to identify enrollees (n=359,368) with opioid prescriptions. Indicators of potential inappropriate use or prescribing included overlapping opioid prescriptions, overlapping opioid and benzodiazepine prescriptions, long acting/extended release opioids for acute pain, and high daily doses. In 2010, Medicaid enrollees with opioid prescriptions obtained an average 6.3 opioid prescriptions, and 40% had at least one indicator of potential inappropriate use or prescribing. These indicators have been linked to opioid-related adverse health outcomes, and methods exist to detect and deter inappropriate use and prescribing of opioids. |
Notes from the field: listeriosis associated with stone fruit - United States, 2014
Jackson BR , Salter M , Tarr C , Conrad A , Harvey E , Steinbock L , Saupe A , Sorenson A , Katz L , Stroika S , Jackson KA , Carleton H , Kucerova Z , Melka D , Strain E , Parish M , Mody RK . MMWR Morb Mortal Wkly Rep 2015 64 (10) 282-3 On July 19, 2014, a packing company in California (company A) voluntarily recalled certain lots of stone fruits, including whole peaches, nectarines, plums, and pluots, because of concern about contamination with Listeria monocytogenes based on internal company testing. On July 31, the recall was expanded to cover all fruit packed at their facility during June 1-July 17. After the initial recall, clinicians, state and local health departments, CDC, and the Food and Drug Administration (FDA) received many inquiries about listeriosis from concerned consumers, many of whom had received automated telephone calls informing them that they had purchased recalled fruit. During July 19-31, the CDC Listeria website received >500,000 page views, more than seven times the views received during the previous 52 weeks. However, no molecular information from L. monocytogenes isolates was available to assess whether human illnesses might be linked to these products. |
Estimating the attack rate of pregnancy-associated listeriosis during a large outbreak
Imanishi M , Routh JA , Klaber M , Gu W , Vanselow MS , Jackson KA , Sullivan-Chang L , Heinrichs G , Jain N , Albanese B , Callaghan WM , Mahon BE , Silk BJ . Infect Dis Obstet Gynecol 2015 2015 201479 BACKGROUND: In 2011, a multistate outbreak of listeriosis linked to contaminated cantaloupes raised concerns that many pregnant women might have been exposed to Listeria monocytogenes. Listeriosis during pregnancy can cause fetal death, premature delivery, and neonatal sepsis and meningitis. Little information is available to guide healthcare providers who care for asymptomatic pregnant women with suspected L. monocytogenes exposure. METHODS: We tracked pregnancy-associated listeriosis cases using reportable diseases surveillance and enhanced surveillance for fetal death using vital records and inpatient fetal deaths data in Colorado. We surveyed 1,060 pregnant women about symptoms and exposures. We developed three methods to estimate how many pregnant women in Colorado ate the implicated cantaloupes, and we calculated attack rates. RESULTS: One laboratory-confirmed case of listeriosis was associated with pregnancy. The fetal death rate did not increase significantly compared to preoutbreak periods. Approximately 6,500-12,000 pregnant women in Colorado might have eaten the contaminated cantaloupes, an attack rate of ~1 per 10,000 exposed pregnant women. CONCLUSIONS: Despite many exposures, the risk of pregnancy-associated listeriosis was low. Our methods for estimating attack rates may help during future outbreaks and product recalls. Our findings offer relevant considerations for management of asymptomatic pregnant women with possible L. monocytogenes exposure. |
Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations.
Boylan B , Rice AS , De Staercke C , Eyster ME , Yaish HM , Knoll CM , Bean CJ , Miller CH . J Thromb Haemost 2015 13 (6) 1036-42 BACKGROUND: Hemophilia A (HA) is an X-linked bleeding disorder caused by a deficiency in Factor VIII (FVIII). von Willebrand disease (VWD) is characterized by a quantitative or qualitative defect in von Willebrand Factor (VWF). Patients with VWD with severely low VWF or VWD Type 2N (VWD2N), a VWD subtype distinguished by defective VWF binding to FVIII, may have reduced FVIII levels secondary to their VWD. These patients superficially resemble patients with HA, and pose a potential for misdiagnosis. OBJECTIVES: Investigate the unexplained cause of bleeding in HA patients without known FVIII mutations by assessing plasma VWF antigen (VWF:Ag), FVIII binding capacities, and VWF genotypes. PATIENTS/METHODS: Thirty-seven of 1027 patients with HA studied as part of the Hemophilia Inhibitor Research Study lacked identifiable F8 mutations. These patients (cases) and 73 patients with identified F8 mutations (controls) were evaluated for VWF:Ag, patient's VWF capacity to bind FVIII (VWF:FVIIIB), and VWF sequence. RESULTS: Four cases had VWF:Ag <3 IU/dL and VWF mutations consistent with Type3 VWD. Six cases and one control were heterozygous for mutations previously reported to cause Type1 VWD (VWD1) (n=5 cases and 1 control) or predicted to be deleterious by Polyphen2 and SIFT prediction tools (n=1 case). One control had VWF:Ag <30 IU/dl, and seven patients (4 cases and 3 controls), including two cases who were heterozygous for a known VWD2N mutation, had reduced VWF:FVIIIB. CONCLUSIONS: These data emphasize that some patients diagnosed with HA require VWF assessments in order to achieve a comprehensive diagnosis and an optimal treatment strategy. |
Comparative analysis of field-isolate and monkey-adapted Plasmodium vivax genomes.
Chan ER , Barnwell JW , Zimmerman PA , Serre D . PLoS Negl Trop Dis 2015 9 (3) e0003566 Significant insights into the biology of Plasmodium vivax have been gained from the ability to successfully adapt human infections to non-human primates. P. vivax strains grown in monkeys serve as a renewable source of parasites for in vitro and ex vivo experimental studies and functional assays, or for studying in vivo the relapse characteristics, mosquito species compatibilities, drug susceptibility profiles or immune responses towards potential vaccine candidates. Despite the importance of these studies, little is known as to how adaptation to a different host species may influence the genome of P. vivax. In addition, it is unclear whether these monkey-adapted strains consist of a single clonal population of parasites or if they retain the multiclonal complexity commonly observed in field isolates. Here we compare the genome sequences of seven P. vivax strains adapted to New World monkeys with those of six human clinical isolates collected directly in the field. We show that the adaptation of P. vivax parasites to monkey hosts, and their subsequent propagation, did not result in significant modifications of their genome sequence and that these monkey-adapted strains recapitulate the genomic diversity of field isolates. Our analyses also reveal that these strains are not always genetically homogeneous and should be analyzed cautiously. Overall, our study provides a framework to better leverage this important research material and fully utilize this resource for improving our understanding of P. vivax biology. |
Emergence of Highly Pathogenic Avian Influenza A(H5N1) Virus PB1-F2 Variants and Their Virulence in BALB/c Mice.
Kamal RP , Kumar A , Davis CT , Tzeng WP , Nguyen T , Donis RO , Katz JM , York IA . J Virol 2015 89 (11) 5835-46 Influenza A viruses (IAV) express the PB1-F2 protein from an alternate reading frame within the PB1 gene segment. The roles of PB1-F2 are not well understood, but appear to involve modulation of host cell responses. As shown in previous studies, we find that PB1-F2 of mammalian IAV frequently have premature stop codons that are expected to cause truncations of the protein, whereas avian IAV usually express a full-length 90 amino acid PB1-F2. However, in contrast to other avian IAV, recent isolates of highly pathogenic H5N1 influenza viruses had a high proportion of PB1-F2 truncations (15% since 2010; 61% of isolates in 2013) due to several independent mutations that have persisted and expanded in circulating viruses. One natural H5N1 IAV containing a mutated PB1-F2 start codon (i.e., lacking ATG) was 1000-fold more virulent for BALB/c mice than a closely-related H5N1 containing intact PB1-F2. In vitro, we detected expression of an in-frame protein (C-terminal PB1-F2) from downstream ATGs in PB1-F2 plasmids lacking the well-conserved ATG start codon. Transient expression of full-length, truncated (25 amino acids), and PB1-F2 lacking the initiating ATG in mammalian and avian cells had no effect on cell apoptosis or interferon expression in human lung epithelial cells. Full length and C-terminal PB1-F2 mutants co-localized with mitochondria in A549 cells. Close monitoring of alterations of PB1-F2 and their frequency in contemporary avian H5N1 viruses should continue, as such changes may be markers for mammalian virulence. IMPORTANCE: Although most avian influenza viruses are harmless for humans, some (such as highly pathogenic H5N1 avian influenza viruses) are capable of infecting humans and causing severe disease with a high mortality rate. A number of risk factors potentially associated with adaptation to mammalian infection have been noted. Here we demonstrate that the protein PB1-F2 is frequently truncated in recent isolates of highly pathogenic H5N1 viruses. Truncation of PB1-F2 has been proposed to act as an adaptation to mammalian infection. We show that some forms of truncation of PB1-F2 may be associated with increased virulence in mammals. Our data support the assessment of PB1-F2 truncations for genomic surveillance of influenza viruses. |
Complete genomic sequence for an avian group G rotavirus from South Africa.
Stucker KM , Stockwell TB , Nyaga MM , Halpin RA , Fedorova N , Akopov A , Ngoveni H , Peenze I , Seheri ML , Mphahlele MJ , Wentworth DE . Genome Announc 2015 3 (2) We report the first complete sequence for an avian group G rotavirus (RVG) genome from Africa, which is the third publically available RVG genome. These RVG genomes are highly diverse, especially in their VP4, VP7, NSP4, and NSP3 segments, indicating that RVG diversity is comparable to that of rotavirus A. |
Religiosity, spirituality, and HIV risk behaviors among African American women from four rural counties in the southeastern U.S
Ludema C , Doherty IA , White BL , Simpson CA , Villar-Loubet O , McLellan-Lemal E , O'Daniels CM , Adimora AA . J Health Care Poor Underserved 2015 26 (1) 168-81 In a cross-sectional survey of 1,013 African American women from rural Alabama and North Carolina, we examined the relationship of (1) organizational religiosity (i.e., religious service attendance), (2) non-organizational religiosity (e.g., reading religious materials), and (3) spirituality with these outcomes: women's reports of their sexual behaviors and perceptions of their partners' risk characteristics. Women with high non-organizational religiosity, compared with low, had fewer sex partners in the past 12 months (adjusted prevalence ratio (aPR): 0.58, 95% confidence interval (CI): 0.42, 0.80) and were less likely to have concurrent partnerships (aPR: 0.47, 95% CI: 0.30, 0.73). Similar results were observed for spirituality, and protective but weaker associations were observed for organizational religiosity. Weak associations were observed between organizational religiosity, non-organizational religiosity, and spirituality with partners' risk characteristics. Further exploration of how religiosity and spirituality are associated with protective sexual behaviors is needed to promote safe sex for African American women. |
Regional infection control assessment of antibiotic resistance knowledge and practice
Black SR , Weaver KN , Weinstein RA , Hayden MK , Lin MY , Lavin MA , Gerber SI . Infect Control Hosp Epidemiol 2015 36 (4) 381-6 OBJECTIVE: Multidrug-resistant organisms (MDROs) are an increasing burden among healthcare facilities. We assessed facility-level perceived importance of and responses to various MDROs. DESIGN: A pilot survey to assess staffing, knowledge, and the perceived importance of and response to various multidrug resistant organisms (MDROs). SETTING: Acute care and long-term healthcare facilities METHODS: In 2012, a survey was distributed to infection preventionists at ~300 healthcare facilities. Pathogens assessed were Clostridium difficile, carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, multidrug-resistant (defined as bacterial resistance to ≥3 antibiotic classes) Pseudomonas, and extended-spectrum beta-lactamase-producing Escherichia coli. RESULTS: A total of 74 unique facilities responded, including 44 skilled nursing facilities (SNFs) and 30 acute care facilities (ACFs). While ACFs consistently isolated patients with active infections or colonization due to these MDROs, SNFs had more variable responses. SNFs had more multi-occupancy rooms and reported less specialized training in infection control and prevention than did ACFs. Of all facilities with multi-occupancy rooms, 86% employed a cohorting practice for patients, compared with 50% of those without multi-occupancy rooms; 20% of ACFs and 7% of SNFs cohorted staff while caring for patients with the same MDRO. MRSA and C. difficile were identified as important pathogens in ACFs and SNFs, while CRE importance was unknown or was considered important in <50% of SNFs. CONCLUSION: We identified stark differences in human resources, knowledge, policy, and practice between ACFs and SNFs. For regional control of emerging MDROs like CRE, there is an opportunity for public health officials to provide targeted education and interventions. Education campaigns must account for differences in audience resources and baseline knowledge. |
Revisiting standard precautions to reduce antimicrobial resistance in nursing homes
Stone ND . JAMA Intern Med 2015 175 (5) 723-4 The need to address transmission of multidrug-resistant organisms (MDROs) has never been more critical for nursing homes. Nursing home care is increasing in complexity as growing proportions of residents are entering homes directly from acute care hospitals. The post–acute care population experiences health care exposures such as invasive medical devices, wounds, and antibiotic use that are well-established risk factors for MDRO acquisition, colonization, and infection. In this issue of JAMA Internal Medicine, Mody and colleagues1 describe a new approach to reduce MDRO prevalence and incidence of infections in nursing homes through a multifaceted, targeted infection prevention (TIP) intervention. The TIP intervention incorporates an extensive educational curriculum for nursing staff, active surveillance for MDRO colonization and infections, and the preemptive use of gown and gloves during daily care of all residents with indwelling medical devices (eg, urinary catheters, feeding tubes). Using cluster randomization at the facility level, implementation of the TIP intervention resulted in a 23% reduction in MDRO prevalence among residents with indwelling devices in 6 intervention homes compared with 6 usual care homes. In addition, residents in the intervention homes had a significantly lower risk of methicillin-resistant Staphylococcus aureus acquisition (hazard ratio, 0.78; P = .01) and fewer clinically diagnosed catheter-associated urinary tract infections (hazard ratio, 0.54; P = .04). |
Overtreatment of asymptomatic bacteriuria: identifying targets for improvement
Hartley S , Valley S , Kuhn L , Washer LL , Gandhi T , Meddings J , Chenoweth C , Malani AN , Saint S , Srinivasan A , Flanders SA . Infect Control Hosp Epidemiol 2015 36 (4) 470-3 Treatment of asymptomatic bacteriuria contributes to antimicrobial overuse in hospitalized patients. Indications for urine culture, treatment, and targets for improvement were evaluated in 153 patients. Drivers of antimicrobial overuse included fever with an alternative source, altered mental status, and leukocytosis, which led 435 excess days of antimicrobial therapy. |
Risk factors associated with children missing the fourth dose of DTaP vaccination
Zhao Z . Br J Med Med Res 2015 7 (3) 169-179 BACKGROUND: In 2012, reported pertussis reached the highest number of cases (48,277) in the United States since 1955. OBJECTIVES: Estimate the prevalence of children who missed the fourth dose of DTaP (Diphtheria and Tetanus toxoids and acellular Pertussis vaccine) by parents' confidences in vaccines and influences from providers, the timeliness of the first through the third dose of DTaP, and selected socio-demographic characteristics; identify the significant risk factors for non-receipt of the fourth dose of DTaP; and evaluate the unadjusted and adjusted risk ratios for missing the fourth dose of DTaP. METHODS: Data from 16,919 children 19-35 months living in the United States included in the 2011 National Immunization Survey were analyzed. Weighted categorical data analysis and multivariable regression in the context of complex sample survey were applied to assess the prevalence and to determine the independent risk factors. Results: Overall, 14.7% of children missed the fourth dose of DTaP. Children who were late in receiving the third dose of DTaP had significantly higher risk of missing the fourth dose of DTaP than children who were on-time in receiving the third dose of DTaP (adjusted risk ratio (RR) 2.48; 95%CI (1.92, 3.20)). The risk of missing the fourth dose of DTaP was 62% higher among children whose parents reported they didn't have a good relationship with their child's health-care providers than children whose parents reported having good relationship. Compared with the risk of missing the fourth dose of DTaP among children whose parents were confident in the value of vaccines, the risk was significantly higher for the children whose parents lacked confidence (adjusted RR 1.41; 95%CI (1.05, 1.89)). CONCLUSIONS: Timeliness in receiving the first through the third dose of DTaP, influences from providers, and parents' confidence in the value of vaccines are the five significant risk factors for missing the fourth dose of DTaP vaccination. They are all modifiable. Future interventions to improve parental relationships with providers and attitudes toward vaccines could help improve pertussis vaccination coverage. |
Zoster vaccination increases the breadth of CD4+ T cells responsive to varicella zoster virus
Laing KJ , Russell RM , Dong L , Schmid DS , Stern M , Magaret A , Haas JG , Johnston C , Wald A , Koelle DM . J Infect Dis 2015 212 (7) 1022-31 BACKGROUND: The live, attenuated varicella vaccine strain (vOka) is the only licensed therapeutic vaccine. Boost of VZV-specific cellular immunity is a likely mechanism of action. We examined memory CD4+ T-cell responses to each VZV protein at baseline and after zoster vaccination. METHODS: Serial blood samples were collected from 12 subjects vaccinated with Zostavax and immunogenicity confirmed by direct ex vivo VZV-specific T-cell and antibody assays. CD4+ T-cell lines enriched for VZV-specificity were generated and probed for proliferative responses to every VZV protein and selected peptide sets. RESULTS: Zoster vaccination increased the median magnitude (2.3-fold one month after vaccination) and breadth (4.2-fold one month after vaccination) of VZV-specific CD4+ T-cells. Both measures declined by 6 months. The most prevalent responses at baseline included (highest first) VZV ORFs 68, 4, 37, and 63. After vaccination, responses to ORFs 40, 67, 9, 59, 12, 62, and 18 were also prevalent. The immunogenicity of ORF9 and ORF18 were confirmed using peptides, defining a large number of discrete viral CD4 T-cell epitopes. CONCLUSIONS: The breadth and magnitude of the VZV-specific CD4+ T-cell response increases after zoster vaccination. In addition to glycoprotein E (ORF68), we identified antigenic ORFs that may be useful components of subunit vaccines. |
Making hepatitis E a vaccine-preventable disease
Teshale E , Ward JW . N Engl J Med 2015 372 (10) 899-901 A hepatitis E vaccine could become a powerful new tool in the prevention and control of hepatitis E virus transmission and disease. Most immediately, it can have a role in curbing outbreaks of hepatitis E in humanitarian crises. |
Notes from the field: fatal yellow fever vaccine-associated viscerotropic disease - Oregon, September 2014
DeSilva M , Sharma A , Staples E , Arndt B , Shieh WJ , Shames J , Cieslak P . MMWR Morb Mortal Wkly Rep 2015 64 (10) 279-81 In September 2014, a previously healthy Oregon woman in her 60s went to a hospital emergency department with malaise, dyspnea, vomiting, and diarrhea of 3-5 days' duration. She reported no recent travel, ill contacts, or dietary changes. Six days earlier, she had received a single dose of yellow fever vaccine and typhoid vaccine before planned travel to South America. |
The novel adjuvant dmLT promotes dose sparing, mucosal immunity and longevity of antibody responses to the inactivated polio vaccine in a murine model
Norton EB , Bauer DL , Weldon WC , Oberste MS , Lawson LB , Clements JD . Vaccine 2015 33 (16) 1909-15 One option for achieving global polio eradication is to replace the oral poliovirus vaccine (OPV), which has the risk of reversion to wild-type virulence, with the inactivated poliovirus vaccine (IPV) vaccine. Adjuvants and alternate routes of immunization are promising options that may reduce antigen dose in IPV vaccinations, potentially allowing dose sparing and cost savings. Use of adjuvants and alternate routes of immunization could also help promote mucosal immunity, potentially mimicking the protection against intestinal virus shedding seen with OPV. In the current study, we examined the impact of combining the novel adjuvant dmLT with trivalent IPV for dose sparing, induction of mucosal immunity and increasing longevity of anti-poliovirus (PV) responses in a mouse model following either intradermal (ID) or intramuscular (IM) delivery. We found that non-adjuvanted ID delivery was not superior to IM delivery for fractional dose sparing, but was associated with development of mucosal immunity. Vaccination with IPV+dmLT promoted serum anti-PV neutralizing antibodies with fractional IPV doses by either IM or ID delivery, achieving at least five-fold dose sparing above non-adjuvanted fractional doses. These responses were most noticeable with the PV1 component of the trivalent vaccine. dmLT also promoted germinal center formation and longevity of serum anti-PV neutralizing titers. Lastly, dmLT enhanced mucosal immunity, as defined by fecal and intestinal anti-PV IgA secretion, when included in IPV immunization by ID or IM delivery. These studies demonstrate that dmLT is an effective adjuvant for either IM or ID delivery of IPV. Inclusion of dmLT in IPV immunizations allows antigen dose sparing and enhances mucosal immunity and longevity of anti-PV responses. |
Impact of 10-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children up to two years of age in Brazil
Grando IM , Moraes Cd , Flannery B , Ramalho WM , Horta MA , Pinho DL , Nascimento GL . Cad Saude Publica 2015 31 (2) 276-84 The objective of this study was to analyze the impact of vaccination against Streptococcus pneumoniae on the morbidity and mortality from pneumococcal meningitis in children ≤ 2 years in Brazil, from 2007 to 2012. This is a descriptive study and ecological analysis using data from the Information System on Notifiable Diseases. Pre-vaccination (2007-2009) and post-vaccination (2011-2012) periods were defined to compare incidence rates and mortality. A total of 1,311 cases and 430 deaths were reported during the study period. Incidence decreased from 3.70/100,000 in 2007 to 1.84/100,000 in 2012, and mortality decreased from 1.30/100,000 to 0.40/100,000, or 50% and 69% respectively, with the greatest impact in the 6-11 month age group. This decrease in Pneumococcal meningitis morbidity and mortality rates two years after introduction of the 10-valent pneumococcal conjugate vaccine suggests its effectiveness. |
Accelerating measles elimination and strengthening routine immunization services in Guizhou Province, China, 2003-2009
Zuo S , Cairns L , Hutin Y , Liang X , Tong Y , Zhu Q , Zhang D , Lee LA , Strebel P , Quick L . Vaccine 2015 33 (17) 2050-5 BACKGROUND: To develop a successful model for accelerating measles elimination in poor areas of China, we initiated a seven-year project in Guizhou, one of the poorest provinces, with reported highest measles incidence of 360 per million population in 2002. METHODS: Project strategies consisted of strengthening routine immunization services, enforcement of school entry immunization requirements at kindergarten and school, conducting supplemental measles immunization activities (SIAs), and enhancing measles surveillance. We measured coverage of measles containing vaccines (MCV) by administrative reporting and population-based sample surveys, systematic random sampling surveys, and convenience sampling surveys for routine immunization services, school entry immunization, and SIAs respectively. We measured impact using surveillance based measles incidence. RESULTS: Routine immunization coverage of the 1st dose of MCV (MCV1) increased from 82% to 93%, while 2nd dose of MCV (MCV2) coverage increased from 78% to 91%. Enforcement of school entry immunization requirements led to an increase in MCV2 coverage from 36% on primary school entry in 2004 to 93% in 2009. Province-wide SIAs achieved coverage greater than 90%. The reported annual incidence of measles dropped from 200 to 300 per million in 2003 to 6 per million in 2009, and sustained at 0.9-2.2 per million in 2010-2013. CONCLUSIONS: This project found that a package of strategies including periodic SIAs, strengthened routine immunization, and enforcing school entry immunization requirements, was an effective approach toward achieving and sustaining measles elimination in less-developed area of China. |
Spot the difference-development of a syndrome based protein microarray for specific serological detection of multiple flavivirus infections in travelers.
Cleton NB , Godeke GJ , Reimerink J , Beersma MF , Doorn HR , Franco L , Goeijenbier M , Jimenez-Clavero MA , Johnson BW , Niedrig M , Papa A , Sambri V , Tami A , Velasco-Salas ZI , Koopmans MP , Reusken CB . PLoS Negl Trop Dis 2015 9 (3) e0003580 BACKGROUND: The family Flaviviridae, genus Flavivirus, holds many of the world's most prevalent arboviral diseases that are also considered the most important travel related arboviral infections. In most cases, flavivirus diagnosis in travelers is primarily based on serology as viremia is often low and typically has already been reduced to undetectable levels when symptoms set in and patients seek medical attention. Serological differentiation between flaviviruses and the false-positive results caused by vaccination and cross-reactivity among the different species, are problematic for surveillance and diagnostics of flaviviruses. Their partially overlapping geographic distribution and symptoms, combined with increase in travel, and preexisting antibodies due to flavivirus vaccinations, expand the need for rapid and reliable multiplex diagnostic tests to supplement currently used methods. GOAL: We describe the development of a multiplex serological protein microarray using recombinant NS1 proteins for detection of medically important viruses within the genus Flavivirus. Sera from clinical flavivirus patients were used for primary development of the protein microarray. RESULTS: Results show a high IgG and IgM sensitivity and specificity for individual NS1 antigens, and limited cross reactivity, even within serocomplexes. In addition, the serology based on this array allows for discrimination between infection and vaccination response for JEV vaccine, and no cross-reactivity with TBEV and YFV vaccine induced antibodies when testing for antibodies to other flaviviruses. CONCLUSION: Based on these data, multiplex NS1-based protein microarray is a promising tool for surveillance and diagnosis of flaviviruses. |
Nucleic acid testing by public health referral laboratories for public health laboratories using the U.S. HIV diagnostic testing algorithm.
Wesolowski LG , Wroblewski K , Bennett SB , Parker MM , Hagan C , Ethridge SF , Rhodes J , Sullivan TJ , Ignacio-Hernando I , Werner BG , Owen SM . J Clin Virol 2015 65 6-10 BACKGROUND: Many public health laboratories adopting the U.S. HIV laboratory testing algorithm do not have a nucleic acid test (NAT), which is needed when the third- or fourth-generation HIV screening immunoassay is reactive and the antibody-based supplemental test is non-reactive or indeterminate. OBJECTIVES: Among public health laboratories utilizing public health referral laboratories for NAT conducted as part of the algorithm, we evaluated the percentage of screening immunoassays needing NAT, the number of specimens not meeting APTIMA (NAT) specifications, time to APTIMA result, the proportion of acute infections (i.e., reactive APTIMA) among total infections, and screening immunoassay specificity. STUDY DESIGN: From August 2012 to April 2013, 22 laboratories enrolled to receive free APTIMA (NAT) at New York or Florida public health referral laboratories. Data were analyzed for testing conducted until June 2013. RESULTS: Submitting laboratories conducted a median of 4778 screening immunoassays; 0-1.3% (median 0.2%) needed NAT. Of 140 specimens received, 9 (6.4%) did not meet NAT specifications. The median time from specimen collection to reporting the 11 reactive NAT results was ten days, including six days from receipt in the submitting laboratory to shipment to the referral laboratory. Acute infections ranged from 0 to 12.5% (median 0%) of total infections. Third- and fourth-generation immunoassays met package insert specificity values. CONCLUSIONS: Public health referral laboratories provide a feasible option for conducting NAT. Reducing the time from specimen collection to submission of specimens for NAT is an important step toward maximizing the public health impact of identifying acute infections. |
A microneedle patch containing measles vaccine is immunogenic in non-human primates
Edens C , Collins ML , Goodson JL , Rota PA , Prausnitz MR . Vaccine 2015 33 (37) 4712-8 Very high vaccination coverage is required to eliminate measles, but achieving high coverage can be constrained by the logistical challenges associated with subcutaneous injection. To simplify logistics of vaccine delivery, a patch containing micron-scale polymeric needles was formulated to encapsulate the standard dose of measles vaccine (1000 TCID50) and the immunogenicity of the microneedle patch was compared with subcutaneous injection in rhesus macaques. The microneedle patch was administered without reconstitution with diluent, dissolved in skin within 10min, and caused only mild, transient skin erythema. Both groups of rhesus macaques generated neutralizing antibody responses to measles that were consistent with protection and the neutralizing antibody titers were equivalent. In addition, the microneedle patches maintained an acceptable level of potency after storage at elevated temperature suggesting improved thermostability compared to standard lyophilized vaccine. In conclusion, a measles microneedle patch vaccine was immunogenic in non-human primates, and this approach offers a promising delivery method that could help increase vaccination coverage. |
The effect of cerium oxide nanoparticle valence state on reactive oxygen species and toxicity
Dunnick KM , Pillai R , Pisane KL , Stefaniak AB , Sabolsky EM , Leonard SS . Biol Trace Elem Res 2015 166 (1) 96-107 Cerium oxide (CeO2) nanoparticles, which are used in a variety of products including solar cells, gas sensors, and catalysts, are expected to increase in industrial use. This will subsequently lead to additional occupational exposures, making toxicology screenings crucial. Previous toxicology studies have presented conflicting results as to the extent of CeO2 toxicity, which is hypothesized to be due to the ability of Ce to exist in both a +3 and +4 valence state. Thus, to study whether valence state and oxygen vacancy concentration are important in CeO2 toxicity, CeO2 nanoparticles were doped with gadolinium to adjust the cation (Ce, Gd) and anion (O) defect states. The hypothesis that doping would increase toxicity and decrease antioxidant abilities as a result of increased oxygen vacancies and inhibition of +3 to +4 transition was tested. Differences in toxicity and reactivity based on valence state were determined in RLE-6TN rat alveolar epithelial and NR8383 rat alveolar macrophage cells using enhanced dark field microscopy, electron paramagnetic resonance (EPR), and annexin V/propidium iodide cell viability stain. Results from EPR indicated that as doping increased, antioxidant potential decreased. Alternatively, doping had no effect on toxicity at 24 h. The present results imply that as doping increases, thus subsequently increasing the Ce3+/Ce4+ ratio, antioxidant potential decreases, suggesting that differences in reactivity of CeO2 are due to the ability of Ce to transition between the two valence states and the presence of increased oxygen vacancies, rather than dependent on a specific valence state. |
Effect of external airflow resistive load on postural and exercise-associated cardiovascular and pulmonary responses in pregnancy: a case control study
Kim JH , Roberge RJ , Powell JB . BMC Pregnancy Childbirth 2015 15 45 BACKGROUND: Facial coverings (e.g., balaclavas, niqabs, medical/surgical masks, respirators, etc.), that impose low levels of airflow resistive loads, are worn by millions of pregnant women worldwide, but little data exist addressing their impact on pregnancy-associated cardiovascular and pulmonary responses. METHODS: 16 pregnant and 16 non-pregnant women were monitored physiologically (heart rate, blood pressure, mean arterial pressure, total peripheral resistance, stroke volume, cardiac output, oxygen saturation, transcutaneous carbon dioxide, fetal heart rate) and subjectively (exertion) for 1 h of mixed sedentary postural activity (sitting, standing) and moderate exercise (bicycle ergometer) with and without wearing N95 filtering facepiece respirators with filter resistive loads of 94.1 Pa (9.6 mm H2O) - 119.6 Pa (12.2 mm H2O) pressure. RESULTS: The external airflow resistive loads were associated with increases in diastolic pressure (p = 0.004), mean arterial pressure (p = 0.01), and subjective exertion score (p < 0.001) of all study subjects. No significant differences were noted with the external resistive loads between the pregnant and non-pregnant groups for any cardiovascular, pulmonary and subjective variable over 1 h. CONCLUSIONS: Low external airflow resistive loads, during combined sedentary postural activity and moderate exercise over 1 h, were associated with increases in the diastolic and mean arterial pressures of all study subjects, but pregnancy itself was not associated with any significant differences in physiologic or subjective responses to the external airway resistive loads utilized in the study. |
Evaluation of treponemal serum tests performed on cerebrospinal fluid for diagnosis of neurosyphilis
Guarner J , Jost H , Pillay A , Sun Y , Cox D , Notenboom R , Workowski K . Am J Clin Pathol 2015 143 (4) 479-84 OBJECTIVES: We evaluated the use of treponemal serum tests in cerebrospinal fluid (CSF) to diagnose neurosyphilis since CSF-Venereal Disease Research Laboratory (VDRL) is specific but lacks sensitivity. METHODS: We tested CSF specimens using the following treponemal serum tests: INNO-LIA, Treponema pallidum particle agglutination (TP-PA), Trep-Sure, and Maxi-Syph. The reference standard to calculate sensitivity and specificity was having two or more reactive/positive tests on CSF. RESULTS: The reference standard group included 11 cases that fulfilled the definition of neurosyphilis (reactive CSF-VDRL plus symptoms) and three cases that did not fulfill the definition: two cases had neurologic symptoms but a nonreactive CSF-VDRL, and one had several positive CSF syphilis tests (reactive VDRL and positive treponemal and syphilis polymerase chain reaction) but no history (referred sample). Controls included 18 patients in whom a CSF-VDRL was performed the same week as patients in the reference group. The sensitivity was 85.7% (12/14) for CSF-VDRL, 92.9% (13/14) for Trep-Sure, 100% (10/10) for Maxi-Syph, 92.3% (12/13) for INNO-LIA, and 83.3% (10/12) for TP-PA. Specificity was 100% for all tests. CONCLUSIONS: Treponemal serum tests performed on CSF were useful in identifying two patients with nonreactive CSF-VDRL. |
An ex vivo avian leukocyte culture model for West Nile virus infection
Dietrich EA , Bowen RA , Brault AC . J Virol Methods 2015 218 19-22 West Nile virus (WNV) replicates in a wide variety of avian species, which act as amplification hosts. In particular, WNV generates high titers and elicits severe pathology in American crows (AMCRs; Corvus brachyrhynchos), a species that has been used as a sentinel for WNV transmission. Although the specific cellular targets of WNV replication in AMCRs are not well defined, preliminary evidence suggests that leukocytes may be an important target of early replication. Therefore, development of a protocol for ex vivo culture of AMCR leukocytes as a model for assessing differential avian host susceptibility is described herein. WNV growth in these cultures mirrored in vivo viremia profiles. These data indicate that ex vivo leukocyte cultures can be used for preliminary pathological assessment of novel WNV strains and potentially of other flaviviruses that use avian reservoir hosts. |
Hatchery spray cabinet administration does not damage avian coronavirus infectious bronchitis virus vaccine based on analysis by electron microscopy and virus titration
Roh HJ , Jordan BJ , Hilt DA , Ard MB , Jackwood MW . Avian Dis 2015 59 (1) 149-152 Previous studies in our laboratory showed that the Arkansas-Delmarva Poultry Industry (Ark-DPI) vaccine given to 1-day-old chickens by hatchery spray cabinet replicated poorly and failed to adequately protect broilers against homologous virus challenge, whereas the same vaccine given by eye-drop did replicate and the birds were protected following homologous virus challenge. To determine if mechanical damage following spray application plays a role in failure of the Ark-DPI vaccine, we examined the morphology of three Ark-DPI vaccines from different manufacturers using an electron microscope and included a Massachusetts (Mass) vaccine as control. One of the Ark-DPI vaccines (vaccine A) and the Mass vaccine had significantly (P < 0.005) fewer spikes than the other two Ark-DPI vaccines. We also found that the Ark-DPI and Mass vaccines had significantly (P < 0.005) fewer spike proteins per virus particle when compared to their respective challenge viruses. This observation is interesting and may provide some insight into the mechanism behind infectious bronchitis virus attenuation. No obvious differences were observed in virus morphology and no consistent trend in the number of spikes per virion was found in before-and after-spray samples. We also determined the vaccine titer before and after spray in embryonated eggs and found that both Ark-DPI and Mass vaccines had a similar drop in titer, 0.40 log10 and 0.36 log10, respectively. Based on these data, it appears that mechanical damage to the Ark-DPI vaccine is not occurring when delivered by a hatchery spray cabinet, suggesting that some other factor is contributing to the failure of that vaccine when given by that method. |
CD4 enumeration technologies: a systematic review of test performance for determining eligibility for antiretroviral therapy
Peeling RW , Sollis KA , Glover S , Crowe SM , Landay AL , Cheng B , Barnett D , Denny TN , Spira TJ , Stevens WS , Crowley S , Essajee S , Vitoria M , Ford N . PLoS One 2015 10 (3) e0115019 BACKGROUND: Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. METHODS AND FINDINGS: Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/mul over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/mul, bias ranged from -35.2 to +13.1 cells/mul while at counts >350 cells/mul, bias ranged from -70.7 to +47 cells/mul, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/mul ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. CONCLUSIONS: A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed. |
Clinical laboratory analytics: challenges and promise for an emerging discipline
Shirts BH , Jackson BR , Baird GS , Baron JM , Clements B , Grisson R , Hauser RG , Taylor JR , Terrazas E , Brimhall B . J Pathol Inform 2015 6 9 The clinical laboratory is a major source of health care data. Increasingly these data are being integrated with other data to inform health system-wide actions meant to improve diagnostic test utilization, service efficiency, and "meaningful use." The Academy of Clinical Laboratory Physicians and Scientists hosted a satellite meeting on clinical laboratory analytics in conjunction with their annual meeting on May 29, 2014 in San Francisco. There were 80 registrants for the clinical laboratory analytics meeting. The meeting featured short presentations on current trends in clinical laboratory analytics and several panel discussions on data science in laboratory medicine, laboratory data and its role in the larger healthcare system, integrating laboratory analytics, and data sharing for collaborative analytics. One main goal of meeting was to have an open forum of leaders that work with the "big data" clinical laboratories produce. This article summarizes the proceedings of the meeting and content discussed. |
Comparison of traditional intranasal and aerosol inhalation inoculation of mice with influenza A viruses
Belser JA , Gustin KM , Katz JM , Maines TR , Tumpey TM . Virology 2015 481 107-112 Intranasal instillation of virus in a liquid suspension (IN) is the most frequently employed method to inoculate small mammalian models with influenza virus, but does not reflect a natural route of exposure. In contrast, inoculation via aerosol inhalation (AR) more closely resembles human exposure to influenza virus. Studies in mice have yielded conflicting results regarding virulence induced by virus inoculated by these routes, and have not controlled for potential strain-specific differences, or examined contemporary influenza viruses and avian viruses with pandemic potential. We used a whole-body AR inoculation method to compare infectivity and disease progression of a highly pathogenic H5N1, a low pathogenic H7N9, and a 2009 H1N1 virus with traditional IN inoculation in the mouse model. Generally comparable levels of morbidity and mortality were observed with all viruses examined using either inoculation route, indicating that both IN and AR delivery are appropriate for murine studies investigating influenza virus pathogenicity. |
Defining the needs for next generation assays for tuberculosis
Denkinger CM , Kik SV , Cirillo DM , Casenghi M , Shinnick T , Weyer K , Gilpin C , Boehme CC , Schito M , Kimerling M , Pai M . J Infect Dis 2015 211 S29-s38 To accelerate the fight against tuberculosis, major diagnostic challenges need to be addressed urgently. Post-2015 targets are unlikely to be met without the use of novel diagnostics that are more accurate and can be used closer to where patients first seek care in affordable diagnostic algorithms. This article describes the efforts by the stakeholder community that led to the identification of the high-priority diagnostic needs in tuberculosis. Subsequently target product profiles for the high-priority diagnostic needs were developed and reviewed in a World Health Organization (WHO)-led consensus meeting. The high-priority diagnostic needs included (1) a sputum-based replacement test for smear-microscopy; (2) a non-sputum-based biomarker test for all forms of tuberculosis, ideally suitable for use at levels below microscopy centers; (3) a simple, low cost triage test for use by first-contact care providers as a rule-out test, ideally suitable for use by community health workers; and (4) a rapid drug susceptibility test for use at the microscopy center level. The developed target product profiles, along with complimentary work presented in this supplement, will help to facilitate the interaction between the tuberculosis community and the diagnostics industry with the goal to lead the way toward the post-2015 global tuberculosis targets. |
Differences in type I interferon signaling antagonism by dengue viruses in human and non-human primate cell lines
Medina FA , Torres-Malave G , Chase AJ , Santiago GA , Medina JF , Santiago LM , Munoz-Jordan JL . PLoS Negl Trop Dis 2015 9 (3) e0003468 BACKGROUND/OBJECTIVES: In vitro studies have shown that dengue virus (DENV) can thwart the actions of interferon (IFN)-alpha/beta and prevent the development of an antiviral state in infected cells. Clinical studies looking at gene expression in patients with severe dengue show a reduced expression of interferon stimulated genes compared to patients with dengue fever. Interestingly, there are conflicting reports as to the ability of DENV or other flaviviruses to inhibit IFN-alpha/beta signaling. METHODOLOGY/PRINCIPAL FINDINGS: In order to determine the relative inhibition of IFN-alpha/beta signaling by DENVs, a method combining flow cytometry and a four-parameter logistic regression model was established. A representative isolate from DENV-1, -3 and -4 and seventeen representative isolates encompassing all DENV-2 genotypes were evaluated. All of the DENVs evaluated in this study were capable of inhibiting IFN-alpha/beta signaling. Most of the strains were able to inhibit IFN-alpha/beta to a degree similar to DENV strain 16681; however, DENV-2 sylvatic strains demonstrated an increased inhibition of phosphorylated signal transducer and activator of transcription (pSTAT1). Surprisingly, we were unable to observe inhibition of pSTAT1 by DENV-2 sylvatic strains or the Asian strain 16681 in non-human primate (NHP) cell lines. Analysis in primary Rhesus macaque dendritic cells suggests that DENVs are capable of inhibiting IFN signaling in these cells. However, contrary to human dendritic cells, production of IFN-alpha was detected in the supernatant of DENV-infected Rhesus macaque dendritic cells. CONCLUSIONS: The ability of DENVs to inhibit IFN-alpha/beta signaling is conserved. Although some variation in the inhibition was observed, the moderate differences may be difficult to correlate with clinical outcomes. DENVs were unable to inhibit pSTAT1 in NHP cell lines, but their ability to inhibit pSTAT1 in primary Rhesus macaque dendritic cells suggests that this may be a cell specific phenomena or due to the transformed nature of the cell lines. |
Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism and blood folate concentrations: a systematic review and meta-analysis of trials and observational studies.
Tsang BL , Devine OJ , Cordero AM , Marchetta CM , Mulinare J , Mersereau P , Guo J , Qi YP , Berry RJ , Rosenthal J , Crider KS , Hamner HC . Am J Clin Nutr 2015 101 (6) 1286-94 BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism is a risk factor for neural tube defects. The T allele produces an enzyme with reduced folate-processing capacity, which has been associated with lower blood folate concentrations. OBJECTIVE: We assessed the association between MTHFR C677T genotypes and blood folate concentrations among healthy women aged 12-49 y. DESIGN: We conducted a systematic review of the literature published from January 1992 to March 2014 to identify trials and observational studies that reported serum, plasma, or red blood cell (RBC) folate concentrations and MTHFR C677T genotype. We conducted a meta-analysis for estimates of percentage differences in blood folate concentrations between genotypes. RESULTS: Forty studies met the inclusion criteria. Of the 6 studies that used the microbiologic assay (MA) to measure serum or plasma (S/P) and RBC folate concentrations, the percentage difference between genotypes showed a clear pattern of CC > CT > TT. The percentage difference was greatest for CC > TT [S/P: 13%; 95% credible interval (CrI): 7%, 18%; RBC: 16%; 95% CrI: 12%, 20%] followed by CC > CT (S/P: 7%; 95% CrI: 1%, 12%; RBC: 8%; 95% CrI: 4%, 12%) and CT > TT (S/P: 6%; 95% CrI: 1%, 11%; RBC: 9%; 95% CrI: 5%, 13%). S/P folate concentrations measured by using protein-binding assays (PBAs) also showed this pattern but to a greater extent (e.g., CC > TT: 20%; 95% CrI: 17%, 22%). In contrast, RBC folate concentrations measured by using PBAs did not show the same pattern and are presented in the Supplemental Material only. CONCLUSIONS: Meta-analysis results (limited to the MA, the recommended population assessment method) indicated a consistent percentage difference in S/P and RBC folate concentrations across MTHFR C677T genotypes. Lower blood folate concentrations associated with this polymorphism could have implications for a population-level risk of neural tube defects. |
Sociodemographic attributes and spina bifida outcomes
Schechter MS , Liu T , Soe M , Swanson M , Ward E , Thibadeau J . Pediatrics 2015 135 (4) e957-64 BACKGROUND: A National Spina Bifida Patient Registry (NSBPR) was begun in 2009 to help understand the natural history of spina bifida (SB) and the effects of treatments provided by SB clinics. We used the NSBPR to explore the relationship of sociodemographic characteristics with SB outcomes. METHODS: Using NSBPR data collected in 2009 to 2012, we examined the unadjusted association between demographic characteristics and 4 SB outcomes: bowel continence, bladder continence, mobility, and presence of pressure sores. We then developed multivariable logistic models to explore these relationships while controlling for SB clinic, SB type, and level of lesion. RESULTS: Data were available on 2054 patients <22 years of age from 10 SB clinics. In the multivariable models, older age groups were more likely to have continence and pressure sores and less likely to be community ambulatory. Males and patients without private insurance were less likely to be continent and community ambulatory. Non-Hispanic blacks were less likely to be continent. Level of lesion was associated with all outcomes; SB type was associated with all but pressure sores; and all outcomes except community ambulation showed significant variation across clinic sites. CONCLUSIONS: Sociodemographic attributes are associated with SB outcomes. In particular, males, non-Hispanic blacks, and patients without private insurance have less favorable outcomes, and age has an impact as well. These characteristics need to be considered by clinicians who care for this patient population and factored into case-mix adjustment when evaluating variation in clinical and functional outcomes among different SB clinics. |
Hypertensive disorders and pregnancy-related stroke: frequency, trends, risk factors, and outcomes
Leffert LR , Clancy CR , Bateman BT , Bryant AS , Kuklina EV . Obstet Gynecol 2015 125 (1) 124-31 OBJECTIVE: To evaluate trends and associations of hypertensive disorders of pregnancy with stroke risk and test the hypothesis that hypertensive disorders of pregnancy-associated stroke results in higher rates of stroke-related complications than pregnancy-associated stroke without hypertensive disorders. METHODS: A cross-sectional study was performed using 81,983,216 pregnancy hospitalizations from the 1994-2011 Nationwide Inpatient Sample. Rates of stroke hospitalizations with and without these hypertensive disorders were reported per 10,000 pregnancy hospitalizations. Using logistic regression, adjusted odds ratios (OR) with 95% confidence intervals were obtained. RESULTS: Between 1994-1995 and 2010-2011, the nationwide rate of stroke with hypertensive disorders of pregnancy increased from 0.8 to 1.6 per 10,000 pregnancy hospitalizations (103%), whereas the rate without these disorders increased from 2.2 to 3.2 per 10,000 pregnancy hospitalizations (47%). Women with hypertensive disorders of pregnancy were 5.2 times more likely to have a stroke than those without. Having traditional stroke risk factors (eg, congenital heart disease, atrial fibrillation, sickle cell anemia, congenital coagulation defects) substantially increased the stroke risk among hypertensive disorders of pregnancy hospitalizations: from adjusted OR 2.68 for congenital coagulation defects to adjusted OR 13.1 for congenital heart disease. Stroke-related complications were increased in stroke with hypertensive disorders of pregnancy compared with without (from adjusted OR 1.23 for nonroutine discharge to adjusted OR 1.93 for mechanical ventilation). CONCLUSION: Having traditional stroke risk factors substantially increased the stroke risk among hypertensive disorders of pregnancy hospitalizations. Stroke with hypertensive disorders in pregnancy had two distinctive characteristics: a greater increase in frequency since the mid-1990s and significantly higher stroke-related complication rates. LEVEL OF EVIDENCE: III. |
Brief report: independent validation of autism spectrum disorder case status in the Utah Autism and Developmental Disabilities Monitoring (ADDM) Network site
Bakian AV , Bilder DA , Carbone PS , Hunt TD , Petersen B , Rice CE . J Autism Dev Disord 2015 45 (3) 873-80 An independent validation was conducted of the Utah Autism and Developmental Disabilities Monitoring Network's (UT-ADDM) classification of children with autism spectrum disorder (ASD). UT-ADDM final case status (n = 90) was compared with final case status as determined by independent external expert reviewers (EERs). Inter-rater reliability (ICC = 0.84), specificity [0.83 (95 % CI 0.74-0.90)], and sensitivity [0.99 (95 % CI 0.96-1.00)] were high for ASD case versus non-case classification between UT-ADDM and EER. At least one EER disagreed with UT-ADDM on ASD final case status on nine out of 30 records; however, all three EERs disagreed with UT-ADDM for only one record. Findings based on limited data suggest that children with ASD as identified by UT-ADDM are consistently classified as ASD cases by independent autism experts. |
Healthful food availability in stores and restaurants - American Samoa, 2014
Lee-Kwan SH , Kumar G , Ayscue P , Santos M , McGuire LC , Blanck HM , Nua MT . MMWR Morb Mortal Wkly Rep 2015 64 (10) 276-8 American Samoa, one of the U.S.-affiliated Pacific Islands, has documented the highest prevalence of adults with obesity (75%) in the world. The nutritionally poor food and beverage environment of food retail venues has been suspected to be a contributing factor, although an evaluation of these venues in American Samoa has not been conducted. In January 2014, American Samoa established an Obesity Task Force to develop policies and strategies to combat obesity. To inform the efforts of the task force, the American Samoa Department of Health and CDC conducted a baseline assessment of the availability, pricing, and promotion of healthful foods at retail food venues. Previously validated food environment assessment tools were modified to incorporate American Samoa foods and administered in a geographically representative sample of 70 stores (nine grocery stores and 61 convenience stores) and 20 restaurants. In convenience stores, healthful items were not found as available as less healthful counterparts, and some healthful items were more expensive than their less healthful counterparts. For restaurants, 70% offered at least one healthful entree, whereas only 30% had healthful side dishes, such as vegetables. Actions to promote healthy eating, such as providing calorie information, were rare among restaurants. Improving availability, affordability, and the promotion of healthful foods in American Samoa stores and restaurants could support healthy eating among American Samoa residents. |
A church-based pilot study designed to improve dietary quality for rural, lower Mississippi Delta, African American adults
Tussing-Humphreys LM , Thomson JL , Onufrak SJ . J Relig Health 2015 54 (2) 455-69 We piloted a 6-month, church-based, behavioral intervention, Delta Body and Soul (DBS), for African American (AA) adults in the Lower Mississippi Delta (LMD). DBS was designed to improve overall dietary quality in LMD AA adults. The intervention included six once monthly group-based educational sessions implemented by trained church members. Program implementation, session attendance, congregational feedback, and baseline and post-intervention, demographic, health, behavioral, and clinical parameters were assessed. Participants were predominately AA, female, and overweight or obese. Retention rate was 79 %. High adherence, defined as attendance at four or more educational sessions, was associated with dietary quality improvement and reduced blood glucose. Implementation of the DBS pilot intervention was feasible and may result in dietary quality and clinical improvements. |
Suicide in U.S workplaces, 2003-2010: a comparison with non-workplace suicides
Tiesman HM , Konda S , Hartley D , Menendez CC , Ridenour M , Hendricks S . Am J Prev Med 2015 48 (6) 674-82 INTRODUCTION: Suicide rates have risen considerably in recent years. National workplace suicide trends have not been well documented. The aim of this study is to describe suicides occurring in U.S. workplaces and compare them to suicides occurring outside of the workplace between 2003 and 2010. METHODS: Suicide data originated from the Census of Fatal Occupational Injury database and the Web-Based Injury Statistics Query and Reporting System. Suicide rates were calculated using denominators from the 2013 Current Population Survey and 2000 U.S. population census. Suicide rates were compared among demographic groups with rate ratios and 95% CIs. Suicide rates were calculated and compared among occupations. Linear regression, adjusting for serial correlation, was used to analyze temporal trends. Analyses were conducted in 2013-2014. RESULTS: Between 2003 and 2010, a total of 1,719 people died by suicide in the workplace. Workplace suicide rates generally decreased until 2007 and then sharply increased (p=0.035). This is in contrast with non-workplace suicides, which increased over the study period (p=0.025). Workplace suicide rates were highest for men (2.7 per 1,000,000); workers aged 65-74 years (2.4 per 1,000,000); those in protective service occupations (5.3 per 1,000,000); and those in farming, fishing, and forestry (5.1 per 1,000,000). CONCLUSIONS: The upward trend of suicides in the workplace underscores the need for additional research to understand occupation-specific risk factors and develop evidence-based programs that can be implemented in the workplace. |
General population job exposure matrix applied to a pooled study of prevalent carpal tunnel syndrome
Dale AM , Zeringue A , Harris-Adamson C , Rempel D , Bao S , Thiese MS , Merlino L , Burt S , Kapellusch J , Garg A , Gerr F , Hegmann KT , Eisen EA , Evanoff B . Am J Epidemiol 2015 181 (6) 431-9 A job exposure matrix may be useful for the study of biomechanical workplace risk factors when individual-level exposure data are unavailable. We used job title-based exposure data from a public data source to construct a job exposure matrix and test exposure-response relationships with prevalent carpal tunnel syndrome (CTS). Exposures of repetitive motion and force from the Occupational Information Network were assigned to 3,452 active workers from several industries, enrolled between 2001 and 2008 from 6 studies. Repetitive motion and force exposures were combined into high/high, high/low, and low/low exposure groupings in each of 4 multivariable logistic regression models, adjusted for personal factors. Although force measures alone were not independent predictors of CTS in these data, strong associations between combined physical exposures of force and repetition and CTS were observed in all models. Consistent with previous literature, this report shows that workers with high force/high repetition jobs had the highest prevalence of CTS (odds ratio = 2.14-2.95) followed by intermediate values (odds ratio = 1.09-2.27) in mixed exposed jobs relative to the lowest exposed workers. This study supports the use of a general population job exposure matrix to estimate workplace physical exposures in epidemiologic studies of musculoskeletal disorders when measures of individual exposures are unavailable. |
Assessing occupational exposure to sea lamprey pesticides
Ceballos DM , Beaucham CC , Kurtz K , Musolin K . Int J Occup Environ Health 2015 21 (2) 151-60 BACKGROUND: Sea lampreys are parasitic fish found in lakes of the United States and Canada. Sea lamprey is controlled through manual application of the pesticides 3-trifluoromethyl-4-nitrophenol (TFM) and BayluscideTM into streams and tributaries. 3-Trifluoromethyl-4-nitrophenol may cause irritation and central nervous system depression and Bayluscide may cause irritation, dermatitis, blisters, cracking, edema, and allergic skin reactions. OBJECTIVES: To assess occupational exposures to sea lamprey pesticides. METHODS: We developed a wipe method for evaluating surface and skin contamination with these pesticides. This method was field tested at a biological field station and at a pesticide river application. We also evaluated exposures using control banding tools. RESULTS: We verified TFM surface contamination at the biological station. At the river application, we found surfaces and worker's skin contaminated with pesticides. CONCLUSION: We recommended minimizing exposures by implementing engineering controls and improved use of personal protective equipment. |
Cleaning and disinfecting environmental surfaces in health care: toward an integrated framework for infection and occupational illness prevention
Quinn MM , Henneberger PK , Braun B , Delclos GL , Fagan K , Huang V , Knaack JL , Kusek L , Lee SJ , Le Moual N , Maher KA , McCrone SH , Mitchell AH , Pechter E , Rosenman K , Sehulster L , Stephens AC , Wilburn S , Zock JP . Am J Infect Control 2015 43 (5) 424-34 BACKGROUND: The Cleaning and Disinfecting in Healthcare Working Group of the National Institute for Occupational Safety and Health, National Occupational Research Agenda, is a collaboration of infection prevention and occupational health researchers and practitioners with the objective of providing a more integrated approach to effective environmental surface cleaning and disinfection (C&D) while protecting the respiratory health of health care personnel. METHODS: The Working Group, comprised of >40 members from 4 countries, reviewed current knowledge and identified knowledge gaps and future needs for research and practice. RESULTS: An integrated framework was developed to guide more comprehensive efforts to minimize harmful C&D exposures without reducing the effectiveness of infection prevention. Gaps in basic knowledge and practice that are barriers to an integrated approach were grouped in 2 broad areas related to the need for improved understanding of the (1) effectiveness of environmental surface C&D to reduce the incidence of infectious diseases and colonization in health care workers and patients and (2) adverse health impacts of C&D on health care workers and patients. Specific needs identified within each area relate to basic knowledge, improved selection and use of products and practices, effective hazard communication and training, and safer alternatives. CONCLUSION: A more integrated approach can support multidisciplinary teams with the capacity to maximize effective and safe C&D in health care. |
Assessment of molecular markers for anti-malarial drug resistance after the introduction and scale-up of malaria control interventions in western Kenya.
Shah M , Omosun Y , Lal A , Odero C , Gatei W , Otieno K , Gimnig JE , Kuile Fter , Hawley WA , Nahlen B , Kariuki S , Walker E , Slutsker L , Hamel M , Shi YP . Malar J 2015 14 (75) 75 BACKGROUND: Although it is well known that drug pressure selects for drug-resistant parasites, the role of transmission reduction by insecticide-treated bed nets (ITNs) on drug resistance remains unclear. In this study, the drug resistance profile of current and previous first-line anti-malarials in Kenya was assessed within the context of drug policy change and scale-up of ITNs. National first-line treatment changed from chloroquine (CQ) to sulphadoxine-pyrimethamine (SP) in 1998 and to artemether-lumefantrine (AL) in 2004. ITN use was scaled-up in the Asembo, Gem and Karemo areas of western Kenya in 1997, 1999 and 2006, respectively. METHODS: Smear-positive samples (N=253) collected from a 2007 cross-sectional survey among children in Asembo, Gem and Karemo were genotyped for mutations in pfcrt and pfmdr1 (CQ), dhfr and dhps (SP), and at pfmdr-N86 and the gene copy number in pfmdr1 (lumefantrine). Results were compared among the three geographic areas in 2007 and to retrospective molecular data from children in Asembo in 2001. RESULTS: In 2007, 69 and 85% of samples harboured the pfmdr1-86Y mutation and dhfr/dhps quintuple mutant, respectively, with no significant differences by study area. However, the prevalence of the pfcrt-76T mutation differed significantly among areas (p <0.02), between 76 and 94%, with the highest prevalence in Asembo. Several 2007 samples carried mutations at dhfr-164 L, dhps-436A, or dhps-613T. From 2001 to 2007, there were significant increases in the pfcrt-76T mutation from 82 to 94% (p <0.03), dhfr/dhps quintuple mutant from 62 to 82% (p <0.03), and an increase in the septuple CQ and SP combined mutant haplotype, K76Y86I51R59N108G437E540, from 28 to 39%. The prevalence of the pfmdr1-86Y mutation remained unchanged. All samples were single copy for pfmdr1. CONCLUSIONS: Molecular markers associated with lumefantrine resistance were not detected in 2007. More recent samples will be needed to detect any selective effects by AL. The prevalence of CQ and SP resistance markers increased from 2001 to 2007 in the absence of changes in transmission intensity. In 2007, only the prevalence of pfcrt-76T mutation differed among study areas of varying transmission intensity. Resistant parasites were most likely selected by sustained drug pressure from the continued use of CQ, SP, and mechanistically similar drugs, such as amodiaquine and cotrimoxazole. There was no clear evidence that differences in transmission intensity, as a result of ITN scale-up, influenced the prevalence of drug resistance molecular markers. |
Evaluation of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy: a retrospective birth outcomes study in Mansa, Zambia
Mace KE , Chalwe V , Katalenich BL , Nambozi M , Mubikayi L , Mulele CK , Wiegand RE , Filler SJ , Kamuliwo M , Craig AS , Tan KR . Malar J 2015 14 (69) 69 BACKGROUND: Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) decreases placental parasitaemia, thus improving birth outcomes. Zambian policy recommends monthly SP-IPTp doses given presumptively during pregnancy at each antenatal examination, spaced one month apart after 16 weeks of gestation. The effectiveness of SP-IPTp was evaluated in Zambia where a recent study showed moderate prevalence of Plasmodium falciparum parasites with genetic mutations that confer SP resistance. METHODS: HIV-negative women were enrolled at the time of delivery at two facilities in Mansa, Zambia, an area of high malaria transmission. Women were interviewed and SP exposure was determined by antenatal card documentation or self-reports. Using Poisson regression modelling, the effectiveness of SP-IPTp was evaluated for outcomes of parasitaemia (microscopic examination of maternal peripheral, cord, and placental blood films), maternal anaemia (Hb<11 g/dl), placental infection (histopathology), and infant outcomes (low birth weight (LBW), preterm delivery, and small for gestational age) in women who took 0-4 doses of SP-IPTp. RESULTS: Participants included 435 women, with a median age of 23 years (range 16-44). Thirty-four women took zero doses of SP-IPTp, while 115, 142 and 144 women took one, two, or >=three doses, respectively. Multivariate Poisson regression models considering age, mosquito net usage, indoor residual spraying, urban home, gravidity, facility, wet season delivery, and marital status showed that among paucigravid women >=two doses of SP-ITPp compared to one or less doses was associated with a protective effect on LBW (prevalence ratio (PR) 0.33, 95% confidence interval (CI) 0.12-0.91) and any infection (PR 0.76, CI 0.58-0.99). Multivariate models considering SP-IPTp as a continuous variable showed a protective dose-response association with LBW (paucigravid women: PR 0.54, CI 0.33-0.90, multigravid women: PR 0.63, CI 0.41-0.97). CONCLUSIONS: In Mansa, Zambia, an area of moderate SP resistance, >= two doses of SP-IPTp were associated with a protective effect from malaria in pregnancy, especially among paucigravid women. Each dose of SP-IPTp contributed to a 46 and 37% decrease in the frequency of LBW among paucigravid and multigravid women, respectively. SP-IPTp remains a viable strategy in this context. |
Repeat abortions in New York City, 2010
Toprani A . J Urban Health 2015 92 (3) 593-603 This study aims to describe factors associated with the number of past abortions obtained by New York City (NYC) abortion patients in 2010. We calculated rates of first and repeat abortion by age, race/ethnicity, and neighborhood-level poverty and the mean number of self-reported past abortions by age, race/ethnicity, neighborhood-level poverty, number of living children, education, payment method, marital status, and nativity. We used negative binomial regression to predict number of past abortions by patient characteristics. Of the 76,614 abortions reported for NYC residents in 2010, 57 % were repeat abortions. Repeat abortions comprised >50 % of total abortions among the majority of sociodemographic groups we examined. Overall, mean number of past abortions was 1.3. Mean number of past abortions was higher for women aged 30-34 years (1.77), women with ≥5 children (2.50), and black non-Hispanic women (1.52). After multivariable regression, age, race/ethnicity, and number of children were the strongest predictors of number of past abortions. This analysis demonstrates that, although socioeconomic disparities exist, all abortion patients are at high risk for repeat unintended pregnancy and abortion. |
Risk of ectopic pregnancy associated with assisted reproductive technology in the United States, 2001-2011
Perkins KM , Boulet SL , Kissin DM , Jamieson DJ . Obstet Gynecol 2015 125 (1) 70-8 OBJECTIVE: To assess national trends in ectopic pregnancy incidence among assisted reproductive technology users and identify risk factors associated with ectopic pregnancy. METHODS: We identified 553,577 pregnancies reported to the National ART Surveillance System between 2001 and 2011. Of those, 9,480 were ectopic, of which 485 were heterotopic. As a result of small numbers, ectopic and heterotopic pregnancies were combined for analysis. We assessed temporal trends in annual ectopic pregnancy rates using Poisson regression. We used log-binomial regression models with generalized estimating equations for correlated outcomes within clinics to calculate unadjusted and adjusted risk ratios for the association between ectopic pregnancy and selected patient characteristics and treatment factors. RESULTS: The rate of ectopic pregnancy declined from 2.0% (n=735, 95% confidence interval [CI] 1.9-2.2) in 2001 to 1.6% (n=968, 95% CI 1.5-1.7) in 2011 (P for trend <.001). The ectopic pregnancy rate ranged from 2.0% (n=7,469, 95% CI 1.9-2.0) for fresh, nondonor cycles to 1.0% (n=641, 95% CI 0.9-1.1) for fresh, donor cycles. Among fresh, nondonor cycles, the rate of ectopic pregnancy was 1.6% (95% CI 1.4-1.7) when one embryo was transferred compared with 1.7% (95% CI 1.7-1.8), 2.2% (95% CI 2.1-2.3), and 2.5% (95% CI 2.4-2.6) when two, three, or four or more embryos were transferred, respectively (adjusted risk ratios 1.11, 95% CI 0.94-0.30; 1.33, 95% CI 1.12-1.56; and 1.49, 95% CI 1.25-1.78). CONCLUSION: Ectopic pregnancy incidence after assisted reproductive technology has decreased over time, but factors such as multiple embryo transfer increase the risk of ectopic pregnancy. LEVEL OF EVIDENCE: II. |
Trends and correlates of monozygotic twinning after single embryo transfer
Kanter JR , Boulet SL , Kawwass JF , Jamieson DJ , Kissin DM . Obstet Gynecol 2015 125 (1) 111-7 OBJECTIVE: To evaluate trends of monozygotic twinning after single embryo transfer and its association with patient and treatment factors. METHODS: Our retrospective cohort study included 28,596 pregnancies after fresh, nondonor single embryo transfer during 2003-2012 reported to the National ART Surveillance System. We examined trends of monozygotic twin pregnancies (number of fetal heart tones on first-trimester ultrasonography more than one or number of neonates born more than one) and assessed patient and treatment factors for monozygotic twin compared with singleton pregnancies. Modified Poisson regression models were used to estimate adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for association between monozygotic twinning and selected factors stratified by day 2-3 and day 5-6 transfer. RESULTS: During 2003-2012, the incidence of monozygotic twinning after single embryo transfer was lower for day 2-3 transfers than for day 5-6 transfers (1.71%, 95% CI 1.45-1.98, n=162 compared with 2.50%, 95% CI 2.28-2.73, n=472); the incidence did not change significantly over the study period. Among day 2-3 transfers, assisted hatching increased the risk for monozygotic twinning compared with singletons (adjusted RR 2.16, 95% CI 1.53-3.06); use of intracytoplasmic sperm injection decreased the risk (adjusted RR 0.60, 95% CI 0.42-0.85). Having one or more prior pregnancies increased the risk for monozygotic twinning among day 5-6 transfers (adjusted RR 1.26, 95% CI 1.03-1.53). CONCLUSION: Monozygotic twinning after single embryo transfers was more common among day 5-6 embryo transfers than day 2-3 transfers. Use of assisted hatching was associated with increased risk for monozygotic twinning for day 2-3 transfers. LEVEL OF EVIDENCE: II. |
Association between assisted reproductive technology conception and autism in California, 1997-2007
Fountain C , Zhang Y , Kissin DM , Schieve LA , Jamieson DJ , Rice C , Bearman P . Am J Public Health 2015 105 (5) e1-e9 OBJECTIVES: We assessed the association between assisted reproductive technology (ART) and diagnosed autistic disorder in a population-based sample of California births. METHODS: We performed an observational cohort study using linked records from the California Birth Master Files for 1997 through 2007, the California Department of Developmental Services autism caseload for 1997 through 2011, and the Centers for Disease Control and Prevention's National ART Surveillance System for live births in 1997 through 2007. Participants were all 5 926 251 live births, including 48 865 ART-originated infants and 32 922 cases of autism diagnosed by the Department of Developmental Services. We compared births originated using ART with births originated without ART for incidence of autism. RESULTS: In the full population, the incidence of diagnosed autism was twice as high for ART as non-ART births. The association was diminished by excluding mothers unlikely to use ART; adjustment for demographic and adverse prenatal and perinatal outcomes reduced the association substantially, although statistical significance persisted for mothers aged 20 to 34 years. CONCLUSIONS: The association between ART and autism is primarily explained by adverse prenatal and perinatal outcomes and multiple births. |
Regression analysis for differentially misclassified correlated binary outcomes
Tang L , Lyles RH , King CC , Hogan JW , Lo Y . J R Stat Soc Ser C Appl Stat 2015 64 (3) 433-449 In many epidemiological and clinical studies, misclassification may arise in one or several variables, resulting in potentially invalid analytic results (e.g. estimates of odds ratios of interest) when no correction is made. Here we consider the situation in which correlated binary response variables are subject to misclassification. Building on prior work, we provide an approach to adjust for potentially complex differential misclassification via internal validation sampling applied at multiple study time points. We seek to estimate the parameters of a primary generalized linear mixed model that accounts for baseline and/or time-dependent covariates. The misclassification process is modelled via a second generalized linear model that captures variations in sensitivity and specificity parameters according to time and a set of subject-specific covariates that may or may not overlap with those in the primary model. Simulation studies demonstrate the precision and validity of the method proposed. An application is presented based on longitudinal assessments of bacterial vaginosis conducted in the 'HIV epidemiology research' study. |
Approximate model spaces for model-robust experiment design
Smucker BJ , Drew NM . Technometrics 2015 57 (1) 54-63 Optimal designs depend upon a prespecified model form. A popular and effective model-robust alternative is to design with respect to a set of models instead of just one. However, model spaces associated with experiments of interest are often prohibitively large and so algorithmically generated designs are infeasible. Here, we present a simple method that largely eliminates this problem by choosing a small set of models that approximates the full set and finding designs that are explicitly robust for this small set. We build our procedure on a restricted columnwise-pairwise algorithm, and explore its effectiveness for two model spaces in the literature. For smaller full model spaces, we find that the designs constructed with the new method compare favorably with robust designs that use the full model space, with construction times reduced by orders of magnitude. We also construct designs that heretofore have been unobtainable due to the size of their model spaces. Supplementary material (available online) includes code, designs, and additional results. |
Comparing methods of measuring geographic patterns in temporal trends: an application to county-level heart disease mortality in the United States, 1973 to 2010
Vaughan AS , Kramer MR , Waller LA , Schieb LJ , Greer S , Casper M . Ann Epidemiol 2015 25 (5) 329-335 e3 PURPOSE: To demonstrate the implications of choosing analytical methods for quantifying spatiotemporal trends, we compare the assumptions, implementation, and outcomes of popular methods using county-level heart disease mortality in the United States between 1973 and 2010. METHODS: We applied four regression-based approaches (joinpoint regression, both aspatial and spatial generalized linear mixed models, and Bayesian space-time model) and compared resulting inferences for geographic patterns of local estimates of annual percent change and associated uncertainty. RESULTS: The average local percent change in heart disease mortality from each method was -4.5%, with the Bayesian model having the smallest range of values. The associated uncertainty in percent change differed markedly across the methods, with the Bayesian space-time model producing the narrowest range of variance (0.0-0.8). The geographic pattern of percent change was consistent across methods with smaller declines in the South Central United States and larger declines in the Northeast and Midwest. However, the geographic patterns of uncertainty differed markedly between methods. CONCLUSIONS: The similarity of results, including geographic patterns, for magnitude of percent change across these methods validates the underlying spatial pattern of declines in heart disease mortality. However, marked differences in degree of uncertainty indicate that Bayesian modeling offers substantially more precise estimates. |
Prevalence and patterns of marijuana use among pregnant and non-pregnant women of reproductive age
Ko JY , Farr SL , Tong VT , Creanga AA , Callaghan WM . Am J Obstet Gynecol 2015 213 (2) 201.e1-201.e10 OBJECTIVES: To provide national prevalence, patterns, and correlates of marijuana use in the past month and past 2-12 months among women of reproductive age by pregnancy status. STUDY DESIGN: Data from 2007-2012 National Surveys on Drug Use and Health, a cross-sectional nationally representative survey, identified pregnant (n=4,971) and non-pregnant (n=88,402) women 18-44 years of age. Women self-reported marijuana use in the past month and past 2-12 months (use in the past year, but not in the past month). Chi-square statistics and adjusted prevalence ratios were estimated using a weighting variable to account for the complex survey design and probability of sampling. RESULTS: Among pregnant women and non-pregnant women, respectively, 3.9% (95%CI: [3.2, 4.7]) and 7.6% (95%CI: [7.3, 7.9]) used marijuana in the past month and 7.0% (95%CI:[6.0, 8.2]) and 6.4% (95%CI:[6.2, 6.6]) used in the past 2-12 months. Among past-year marijuana users (n=17,934), use almost daily was reported by 16.2% of pregnant and 12.8% of non-pregnant women; and 18.1% of pregnant and 11.4% of non-pregnant women met criteria for abuse and/or dependence. Approximately 70% of both pregnant and non-pregnant women believe there is slight or no risk of harm from using marijuana once or twice a week. Smokers of tobacco, alcohol users, and other illicit drug users were 2-3 times more likely to use marijuana in the past-year than respective non-users, adjusting for sociodemographic characteristics. CONCLUSION: Over one in ten pregnant and non-pregnant women reported using marijuana in the past 12 months. A considerable percentage of women who used marijuana in the past year were daily users, met abuse and/or dependence criteria, and were poly-substance users. Comprehensive screening, treatment for use of multiple substances, and additional research and patient education on the possible harms of marijuana use are needed for all women of reproductive age. |
Exposure to secondhand tobacco smoke and interventions among pregnant women in China: a systematic review
Zhang L , Hsia J , Tu X , Xia Y , Zhang L , Bi Z , Liu H , Li X , Stanton B . Prev Chronic Dis 2015 12 E35 INTRODUCTION: Smoking prevalence is high among men in China. One result is that a large number of nonsmoking Chinese women may be exposed daily to secondhand smoke (SHS). Exposure is particularly problematic for pregnant women because of potential adverse reproductive effects. To determine the extent of this exposure and to summarize existing intervention studies designed to reduce SHS exposure in China, a systematic review of the literature published from 1995 through 2012 was conducted. METHODS: We searched the PubMed and Wanfang databases for studies published from 1995 through 2012 using various search terms including SHS, pregnant women, and China. Only articles on prevalence of SHS exposure and interventions to reduce exposure to SHS were selected. RESULTS: We identified 132 studies during the initial searches. Eight of 13 eligible studies reported the prevalence of SHS exposure among pregnant women; estimates ranged from 38.9% to 75.1%. Few SHS prevention interventions among pregnant women in China have been studied; we found only 5 such studies. The interventions primarily focused on changing husbands' smoking behaviors; some interventions focused on women's avoidance behaviors. CONCLUSION: Prevalence of exposure to SHS among pregnant women is high in China. Information is limited on effective interventions to protect pregnant women from exposure. The results of this review can provide the basis for the design and evaluation of interventions to help pregnant women avoid SHS exposure. |
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