Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-29 (of 29 Records) |
Query Trace: Skinner B[original query] |
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Engaging transgender women in HIV research in South Africa
van der Merwe LLA , Cloete A , Savva H , Skinner D , November G , Fisher ZZ . BMC Public Health 2023 23 (1) 990 The Botshelo Ba Trans study was the first HIV bio-behavioral survey conducted with transgender women in South Africa. Engaging research with marginalized communities requires clear points of entry, reference points for understanding the internal culture, and establishing trust and understanding. The community-based participatory research approach guided the development and implementation of this study. We conducted a rapid qualitative and pre-surveillance formative assessment between August 2017 to January 2018 and a bio-behavioral survey between July 2018 and March 2019. At the start, a Steering Committee, comprising primarily of transgender women, was established and subsequently provided substantial input into the mixed methods study conducted in Buffalo City, Cape Town, and Johannesburg. Key to the study's success was building trust and establishing ownership of the survey by transgender women recognized as expert knowledge holders. Thus, a community-based participatory research-informed approach enhanced the validity of the data and ensured that we addressed relevant issues. |
Reply to Sayed
Choi Y , Zhang X , Skinner B . J Infect Dis 2019 220 (6) 1083-1084 We appreciate the comments made by Sayed [1] regarding our article [2]. We found that rhesus macaques with experimental hepatitis E virus (HEV) infection demonstrated clinical signs consistent with acute viral hepatitis, viral shedding in feces and serum, and development of antiviral antibody responses that are similar to the natural history of HEV infection in humans [3, 4]. Rhesus macaques are susceptible to infection by HEV genotypes 1–4 and have proved to be a reliable experimental model for studying HEV genotype 1 primary infection and reinfection [2, 5, 6]. As with 2 human volunteer inoculation studies [7, 8], HEV RNA was found in the serum and feces of infected rhesus macaques before the elevation of serum alanine transaminase (ALT) activity [3]. The onset of ALT elevation in the serum and histopathological changes in the liver correlated with immune responses marked by anti-HEV antibody responses and viral clearance from the stool of infected rhesus macaques [3, 5]. Other than nonhuman primates, the experimental studies of HEV infection in pigs, rabbits, and human liver chimeric mice showed no elevation in serum ALT activity [9–11]. |
The HIV care continuum for sexually active transgender women in three metropolitan municipalities in South Africa: findings from a biobehavioural survey 2018-19
Cloete A , Mabaso M , Savva H , van der Merwe LL , Naidoo D , Petersen Z , Kose Z , Mthembu J , Moyo S , Skinner D , Jooste S , Fellows IE , Shiraishi RW , Mwandingi SL , Simbayi LC . Lancet HIV 2023 10 (6) e375-e384 BACKGROUND: Despite high HIV prevalence in transgender women in sub-Saharan Africa, to our knowledge no study presents data across the HIV care continuum for this population in the region. The aim of this study was to estimate HIV prevalence and present data to develop the HIV care continuum indicators for transgender women in three South African metropolitan municipalities. METHODS: Biobehavioural survey data were collected among sexually active transgender women in the metropolitan municipalities of Johannesburg, Buffalo City, and Cape Town, South Africa. Transgender women (aged ≥18 years, self-reporting consensual sex with a man in the 6 months before the survey) were recruited using respondent-driven sampling (RDS). An interviewer-administered questionnaire was used to determine awareness of HIV status; blood specimens were collected on dried blood spots to test for HIV antibodies, antiretroviral treatment (ART) exposure, and viral load suppression. Population-based estimates of HIV 95-95-95 cascade indicators were derived by use of individualised RDS weights with RDS Analyst software. Multivariate stepwise backward logistic regression modelling was used to determine factors associated with each cascade indicator. All eligible participants were included in the final analysis. FINDINGS: Between July 26, 2018, and March 15, 2019, we enrolled 887 sexually active transgender women: 323 in Johannesburg, 305 in Buffalo City, and 259 in Cape Town. HIV prevalence was highest in Johannesburg where 229 (74·1%) of 309 tests were positive (weighted prevalence estimate 63·3%, 95% CI 55·5-70·5), followed by Buffalo City where 121 (43·7%) of 277 were positive (46·1%, 38·7-53·6), and then Cape Town where 122 (48·4%) of 252 were positive (45·6%, 36·7-54·7). In Johannesburg, an estimated 54·2% (95% CI 45·8-62·4) of transgender women with HIV knew their positive status, in Cape Town this was 24·2% (15·4-35·8), and in Buffalo City this was 39·5% (27·1-53·4). Among those who knew their status, 82·1% (73·3-88·5) in Johannesburg, 78·2% (57·9-90·3) in Cape Town, and 64·7% (45·2-80·2) in Buffalo City were on ART. Of those on ART, 34·4% (27·2-42·4) in Johannesburg, 41·2% (30·7-52·6) in Cape Town, and 55·0% (40·7-68·4) in Buffalo City were virally suppressed. INTERPRETATION: Innovative strategies are needed to inform efforts to diagnose and to treat transgender women living with HIV promptly to achieve viral load suppression. Differentiated HIV services tailored to transgender women of race groups other than Black South African, and those with low education attainment and low outreach exposure, innovative testing, and adherence strategies should be developed to improve the HIV cascade for South African transgender women. FUNDING: The US President's Emergency Plan For AIDS Relief and US Centers for Disease Control and Prevention. |
Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: research priorities in health services; diversity, equity, and inclusion; and implementation science
Byams VR , Baker JR , Bailey C , Connell NT , Creary MS , Curtis RG , Dinno A , Guelcher CJ , Kim M , Kulkarni R , Lattimore S , Norris KL , Ramirez L , Skinner MW , Symington S , Tobase P , Vázquez E , Warren BB , Wheat E , Buckner TW . Expert Rev Hematol 2023 16 87-106 BACKGROUND: The National Hemophilia Foundation (NHF) conducted extensive all-stakeholder inherited bleeding disorder (BD) community consultations to inform a blueprint for future research. Sustaining and expanding the specialized and comprehensive Hemophilia Treatment Center care model, to better serve all people with inherited BDs (PWIBD), and increasing equitable access to optimal health emerged as top priorities. RESEARCH DESIGN AND METHODS: NHF, with the American Thrombosis and Hemostasis Network (ATHN), convened multidisciplinary expert working groups (WG) to distill priority research initiatives from consultation findings. WG5 was charged with prioritizing health services research (HSR); diversity, equity, and inclusion (DEI); and implementation science (IS) research initiatives to advance community-identified priorities. RESULTS: WG5 identified multiple priority research themes and initiatives essential to capitalizing on this potential. Formative studies using qualitative and mixed methods approaches should be conducted to characterize issues and meaningfully investigate interventions. Investment in HSR, DEI and IS education, training, and workforce development are vital. CONCLUSIONS: An enormous amount of work is required in the areas of HSR, DEI, and IS, which have received inadequate attention in inherited BDs. This research has great potential to evolve the experiences of PWIBD, deliver transformational community-based care, and advance health equity. | Research into how people get their health care, called health services research, is important to understand if care is being delivered equitably and efficiently. This research figures out how to provide the best care at the lowest cost and finds out if everyone gets equally good care. Diversity and inclusion research focuses on whether all marginalized and minoritized populations (such as a given social standing, race, ethnicity, sex, gender identity, sexuality, age, income, disability status, language, culture, faith, geographic location, or country of birth) receive equitable care. This includes checking whether different populations are all getting the care they need and looking for ways to improve the care. Implementation science studies how to make a potential improvement work in the real world. The improvement could be a new way to diagnose or treat a health condition, a better way to deliver health care or do research, or a strategy to remove barriers preventing specific populations from getting the best available care. The National Hemophilia Foundation focuses on improving the lives of all people with bleeding disorders (BD). They brought BDs doctors, nurses, physical therapists, social workers, professors, and government and industry partners together with people and families living with BDs to discuss research in the areas described above. The group came up with important future research questions to address racism and other biases, and other changes to policies, procedures, and practices to make BD care equitable, efficient, and effective. | eng |
Executive summary: Clinical practice guideline for the evaluation and treatment of children and adolescents with obesity
Hampl SE , Hassink SG , Skinner AC , Armstrong SC , Barlow SE , Bolling CF , Avila Edwards KC , Eneli I , Hamre R , Joseph MM , Lunsford D , Mendonca E , Michalsky MP , Mirza N , Ochoa ER , Sharifi M , Staiano AE , Weedn AE , Flinn SK , Lindros J , Okechukwu K . Pediatrics 2023 151 (2) Obesity is a common, complex, and often persistent chronic disease associated with serious health and social consequences if not treated.1 Yet, despite the disease’s complexity, treatment of obesity can be successful.2–4 The current and long-term health of 14.4 million children and adolescents is affected by obesity,5,6 making it one of the most common pediatric chronic diseases in the United States.5,7,8 | | Obesity has long been stigmatized as a reversible consequence of personal choices but has, in reality, complex genetic, physiologic, socioeconomic, and environmental contributors. An increased understanding of the impact of social determinants of health (SDoHs) on the chronic disease of obesity—along with heightened appreciation of the impact of the chronicity and severity of obesity-related comorbidities—has enabled broader and deeper understanding of the complexity of both obesity risk and treatment.9,10 |
Clinical practice guideline for the evaluation and treatment of children and adolescents with obesity
Hampl SE , Hassink SG , Skinner AC , Armstrong SC , Barlow SE , Bolling CF , Avila Edwards KC , Eneli I , Hamre R , Joseph MM , Lunsford D , Mendonca E , Michalsky MP , Mirza N , Ochoa ER , Sharifi M , Staiano AE , Weedn AE , Flinn SK , Lindros J , Okechukwu K . Pediatrics 2023 151 (2) You have in your hands, or at your fingertips, the first edition of the American Academy of Pediatrics clinical practice guideline for evaluation and management of children and adolescents with overweight and obesity. Putting together this guideline was no small task, and the Academy is grateful to the efforts of all the professionals who contributed to the production of this document. This work is a true testament to their passion and dedication to combatting childhood and adolescent overweight and obesity. |
Development of HEK-293 cell lines constitutively expressing flaviviral antigens for use in diagnostics
Powers JA , Skinner B , Davis BS , Biggerstaff BJ , Robb L , Gordon E , Calvert AE , Chang GJ . Microbiol Spectr 2022 10 (3) e0059222 Flaviviruses are important human pathogens worldwide. Diagnostic testing for these viruses is difficult because many of the pathogens require specialized biocontainment. To address this issue, we generated 39 virus-like particle (VLP)- and nonstructural protein 1 (NS1)-secreting stable cell lines in HEK-293 cells of 13 different flaviviruses, including dengue, yellow fever, Japanese encephalitis, West Nile, St. Louis encephalitis, Zika, Rocio, Ilheus, Usutu, and Powassan viruses. Antigen secretion was stable for at least 10 cell passages, as measured by enzyme-linked immunosorbent assays and immunofluorescence assays. Thirty-five cell lines (90%) had stable antigen expression over 10 passages, with three of these cell lines (7%) increasing in antigen expression and one cell line (3%) decreasing in antigen expression. Antigen secretion in the HEK-293 cell lines was higher than in previously developed COS-1 cell line counterparts. These antigens can replace current antigens derived from live or inactivated virus for safer use in diagnostic testing. IMPORTANCE Serological diagnostic testing for flaviviral infections is hindered by the need for specialized biocontainment for preparation of reagents and assay implementation. The use of previously developed COS-1 cell lines secreting noninfectious recombinant viral antigen is limited due to diminished antigen secretion over time. Here, we describe the generation of 39 flaviviral virus-like particle (VLP)- and nonstructural protein 1 (NS1)-secreting stable cell lines in HEK-293 cells representing 13 medically important flaviviruses. Antigen production was more stable and statistically higher in these newly developed cell lines than in their COS-1 cell line counterparts. The use of these cell lines for production of flaviviral antigens will expand serological diagnostic testing of flaviviruses worldwide. |
Monoclonal antibodies to Cache Valley virus for serological diagnosis.
Skinner B , Mikula S , Davis BS , Powers JA , Hughes HR , Calvert AE . PLoS Negl Trop Dis 2022 16 (1) e0010156 Cache Valley virus (CVV) is a mosquito-borne virus in the genus Orthobunyavirus, family Peribunyaviridae. It was first isolated from a Culiseta inorata mosquito in Cache Valley, Utah in 1956 and is known to circulate widely in the Americas. While only a handful of human cases have been reported since its discovery, it is the causative agent of fetal death and severe malformations in livestock. CVV has recently emerged as a potential viral pathogen causing severe disease in humans. Currently, the only serological assay available for diagnostic testing is plaque reduction neutralization test which takes several days to perform and requires biocontainment. To expand diagnostic capacity to detect CVV infections by immunoassays, 12 hybridoma clones secreting anti-CVV murine monoclonal antibodies (MAbs) were developed. All MAbs developed were found to be non-neutralizing and specific to the nucleoprotein of CVV. Cross-reactivity experiments with related orthobunyaviruses revealed several of the MAbs reacted with Tensaw, Fort Sherman, Tlacotalpan, Maguari, Playas, and Potosi viruses. Our data shows that MAbs CVV14, CVV15, CVV17, and CVV18 have high specific reactivity as a detector in an IgM antibody capture test with human sera. |
HIV outbreaks among people who inject drugs in Europe, North America, and Israel
Des Jarlais DC , Sypsa V , Feelemyer J , Abagiu AO , Arendt V , Broz D , Chemtob D , Seguin-Devaux C , Duwve JM , Fitzgerald M , Goldberg DJ , Hatzakis A , Jipa RE , Katchman E , Keenan E , Khan I , Konrad S , McAuley A , Skinner S , Wiessing L . Lancet HIV 2020 7 (6) e434-e442 During 2011-16, HIV outbreaks occurred among people who inject drugs (PWID) in Canada (southeastern Saskatchewan), Greece (Athens), Ireland (Dublin), Israel (Tel Aviv), Luxembourg, Romania (Bucharest), Scotland (Glasgow), and USA (Scott County, Indiana). Factors common to many of these outbreaks included community economic problems, homelessness, and changes in drug injection patterns. The outbreaks differed in size (from under 100 to over 1000 newly reported HIV cases among PWID) and in the extent to which combined prevention had been implemented before, during, and after the outbreaks. Countries need to ensure high coverage of HIV prevention services and coverage higher than the current UNAIDS recommendation might be needed in areas in which short acting drugs are injected. In addition, monitoring of PWID with special attention for changing drug use patterns, risk behaviours, and susceptible subgroups (eg, PWID experiencing homelessness) needs to be in place to prevent or rapidly detect and contain new HIV outbreaks. |
Unique clindamycin-resistant Clostridioides difficile strain related to fluoroquinolone-resistant epidemic BI/RT027 strain
Skinner AM , Petrella L , Siddiqui F , Sambol SP , Gulvik CA , Gerding DN , Donskey CJ , Johnson SC . Emerg Infect Dis 2020 26 (2) 247-254 During a surveillance study of patients in a long-term care facility and the affiliated acute care hospital in the United States, we identified a Clostridioides difficile strain related to the epidemic PCR ribotype (RT) 027 strain associated with hospital outbreaks of severe disease. Fifteen patients were infected with this strain, characterized as restriction endonuclease analysis group DQ and RT591. Like RT027, DQ/RT591 contained genes for toxin B and binary toxin CDT and a tcdC gene of identical sequence. Whole-genome sequencing and multilocus sequence typing showed that DQ/RT591 is a member of the same multilocus sequence typing clade 2 as RT027 but in a separate cluster. DQ/RT591 produced a similar cytopathic effect as RT027 but showed delayed toxin production in vitro. DQ/RT591 was susceptible to moxifloxacin but highly resistant to clindamycin. Continued surveillance is warranted for this clindamycin-resistant strain that is related to the fluoroquinolone-resistant epidemic RT027 strain. |
Analysis of IgG anti-HEV antibody protective levels during hepatitis E virus reinfection in experimentally infected rhesus macaques
Choi Y , Zhang X , Skinner B . J Infect Dis 2018 219 (6) 916-924 Background: Secondary spread of hepatitis E virus (HEV) infection occurs often in endemic settings in developing countries. The host immune signatures contributing to protection against subsequent HEV reinfection are unknown. Methods: Twelve seroconverted rhesus macaques were re-inoculated with homologous HEV genotype 1 (gt1, Sar-55) and followed for 115 days. HEV RNA, HEV-specific T-cell responses, IgG anti-HEV antibody, and the IgG anti-HEV avidity index were tested. Results: Four animals with baseline IgG anti-HEV levels from 1.5 to 13.4 WHO U/ml evidenced reinfection as determined by HEV RNA in stool, and increase in IgG anti-HEV levels between 63- and 285-fold (P= 0.003). Eight animals with baseline IgG anti-HEV levels from 2.8 to 90.7 WHO U/ml did not develop infection or shed virus in feces, and IgG anti-HEV antibody levels were unchanged (P= 0.017). The four reinfected animals showed a lower HEV-IgG avidity index (average 35.5%) than the 8 protected animals (average 62.1%). HEV-specific IFN- producing T cells were 2-fold higher in reinfected animals (P= 0.018). Conclusions: Pre-existing antibody and high IgG avidity index (>50%) are important factors for protection against HEV reinfection. HEV-specific T cell responses were elevated in reinfected animals after subsequent exposure to HEV. |
Ultra-long-acting removable drug delivery system for HIV treatment and prevention
Kovarova M , Benhabbour SR , Massud I , Spagnuolo RA , Skinner B , Baker CE , Sykes C , Mollan KR , Kashuba ADM , Garcia-Lerma JG , Mumper RJ , Garcia JV . Nat Commun 2018 9 (1) 4156 Non-adherence to medication is an important health care problem, especially in the treatment of chronic conditions. Injectable long-acting (LA) formulations of antiretrovirals (ARVs) represent a viable alternative to improve adherence to HIV/AIDS treatment and prevention. However, the LA-ARV formulations currently in clinical trials cannot be removed after administration even if adverse events occur. Here we show an ultra-LA removable system that delivers drug for up to 9 months and can be safely removed to stop drug delivery. We use two pre-clinical models for HIV transmission and treatment, non-human primates (NHP) and humanized BLT (bone marrow/liver/thymus) mice and show a single dose of subcutaneously administered ultra-LA dolutegravir effectively delivers the drug in both models and show suppression of viremia and protection from multiple high-dose vaginal HIV challenges in BLT mice. This approach represents a potentially effective strategy for the ultra-LA drug delivery with multiple possible therapeutic applications. |
Expression profiles of host immune response-related genes against HEV genotype 3 and genotype 1 infections in rhesus macaques.
Choi YH , Zhang X , Tran C , Skinner B . J Viral Hepat 2018 25 (8) 986-995 Hepatitis E virus (HEV) genotype (gt) 3 infection is food-borne causing sporadic infections in older individuals and gt1 infection is water-borne, often causing epidemics affecting primarily young adults. Although HEV infection causes self-limited disease, gt3 induces chronic infection in immunocompromised individuals. Hepatic host gene expression against gt3 infection remains unknown. Host gene expression profiles for HEV gt1 (n=3) and gt3 (n=7) infections were analyzed in the livers of experimentally infected rhesus macaques. HEV RNA was detected from 2 to 24 days after inoculation (DAI) in stool and serum, elevated alanine aminotransferase (ALT) activity was detected from 7 to 31 DAI, and anti-HEV antibody became detectable between 12 and 42 DAI. All 10 animals cleared the infection between 34 to 68 DAI. We found that 24%, 48%, and 41% of hepatic immune response genes against gt3 infection were upregulated during the early, peak, and decline phases of HEV RNA replication. For gt1 infection, 25% of hepatic immune response-related genes were downregulated during early viremia, but 6%, 34%, and 37% of genes were upregulated at the early, peak and during decline of HEV RNA replication, respectively. Our study demonstrated distinct differences in the expression profiles of host immune response-related genes of HEV gt3 and gt1 infections in experimentally infected rhesus macaques. This article is protected by copyright. All rights reserved. |
Assessment of the immunogenicity of rabies vaccine preserved by vaporization and delivered to the duodenal mucosa of gray foxes (Urocyon cinereoargenteus)
Smith TG , Wu X , Ellison JA , Wadhwa A , Franka R , Langham GL , Skinner BL , Hanlon CA , Bronshtein VL . Am J Vet Res 2017 78 (6) 752-756 OBJECTIVE To assess the immunogenicity of thermostable live-attenuated rabies virus (RABV) preserved by vaporization (PBV) and delivered to the duodenal mucosa of a wildlife species targeted for an oral vaccination program. ANIMALS 8 gray foxes (Urocyon cinereoargenteus). PROCEDURES Endoscopy was used to place RABV PBV (n = 3 foxes), alginate-encapsulated RABV PBV (3 foxes), or nonpreserved RABV (2 foxes) vaccine into the duodenum of foxes. Blood samples were collected weekly to monitor the immune response. Saliva samples were collected weekly and tested for virus shedding by use of a conventional reverse-transcriptase PCR assay. Foxes were euthanized 28 days after vaccine administration, and relevant tissues were collected and tested for presence of RABV. RESULTS 2 of 3 foxes that received RABV PBV and 1 of 2 foxes that received nonpreserved RABV seroconverted by day 28. None of the 3 foxes receiving alginate-encapsulated RABV PBV seroconverted. No RABV RNA was detected in saliva at any of the time points, and RABV antigen or RNA was not detected in any of the tissues obtained on day 28. None of the foxes displayed any clinical signs of rabies. CONCLUSIONS AND CLINICAL RELEVANCE Results for this study indicated that a live-attenuated RABV vaccine delivered to the duodenal mucosa can induce an immune response in gray foxes. A safe, potent, thermostable RABV vaccine that could be delivered orally to wildlife or domestic animals would enhance current rabies control and prevention efforts. |
Juxtaarticular myxoma in a pigtail macaque (Macaca nemestrina)
Skinner BL , Johnson CH , Lacy SH . Comp Med 2016 66 (5) 420-423 A 10-y-old pigtail macaque presented with a subcutaneous, soft-tissue mass overlying the right stifle joint. Here we describe the clinical case and histopathologic and immunohistochemical analysis of this lesion. This case represents the first published report of juxtaarticular myxoma in a pigtail macaque. |
NHF-McMaster guideline on care models for haemophilia management
Pai M , Key NS , Skinner M , Curtis R , Feinstein M , Kessler C , Lane SJ , Makris M , Riker E , Santesso N , Soucie JM , Yeung CH , Iorio A , Schunemann HJ . Haemophilia 2016 22 Suppl 3 6-16 This guideline was developed to identify evidence-based best practices in haemophilia care delivery, and discuss the range of care providers and services that are most important to optimize outcomes for persons with haemophilia (PWH) across the United States. The guideline was developed following specific methods described in detail in this supplement and based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation approach). Direct evidence from published literature and the haemophilia community, as well as indirect evidence from other chronic diseases, were reviewed, synthesized and applied to create evidence-based recommendations. The Guideline panel suggests that the integrated care model be used over non-integrated care models for PWH (conditional recommendation, moderate certainty in the evidence). For PWH with inhibitors and those at high risk for inhibitor development, the same recommendation was graded as strong, with moderate certainty in the evidence. The panel suggests that a haematologist, a specialized haemophilia nurse, a physical therapist, a social worker and round-the-clock access to a specialized coagulation laboratory be part of the integrated care team, over an integrated care team that does not include all of these components (conditional recommendation, very low certainty in the evidence). Based on available evidence, the integrated model of care in its current structure, is suggested for optimal care of PWH. There is a need for further appropriately designed studies that address unanswered questions about specific outcomes and the optimal structure of the integrated care delivery model in haemophilia. |
The prevalence and validity of high, biologically implausible values of weight, height, and BMI among 8.8 million children
Freedman DS , Lawman HG , Pan L , Skinner AC , Allison DB , McGuire LC , Blanck HM . Obesity (Silver Spring) 2016 24 (5) 1132-9 OBJECTIVE: This study assessed the prevalence and consistency of high values of weight, height, and BMI considered to be biologically implausible (BIV) using cut points proposed by WHO among 8.8 million low-income children (13.7 million observations). METHODS: Cross-sectional and longitudinal analyses were performed among 2- to 4-year-olds who were examined from 2008 through 2011. RESULTS: Overall, 2.7% of the body size measurements were classified as BIVs; 95% of these BIVs were very high. Among the subset of children (3.6 million) examined more than once, most of those who initially had a high weight or BMI BIV also had a high BIV at the second examination; odds ratios were >250. Based on several alternative classifications of BIVs, the current cut points likely underestimate the prevalence of obesity by about 1%. CONCLUSIONS: Many of the extremely high values of body size currently flagged as BIVs are unlikely to be errors. Increasing the z-score cut points or using a percentage of the maximum values in the National Health and Nutrition Examination Survey, could improve the balance between removing probable errors and retaining those that are likely correct. |
Viral loads among HIV-infected persons diagnosed with primary and secondary syphilis in 4 US cities: New York City, Philadelphia, PA, Washington, DC, and Phoenix, AZ
Taylor MM , Newman DR , Schillinger JA , Lewis FMT , Furness B , Braunstein S , Mickey T , Skinner J , Eberhart M , Opoku J , Blank S , Peterman TA . J Acquir Immune Defic Syndr 2015 70 (2) 179-185 BACKGROUND: Incident syphilis among HIV-infected persons indicates the ongoing behavioral risk for HIV transmission. Detectable viral loads (VLs) among coinfected cases may amplify this risk. METHODS: Primary and secondary cases reported during 2009-2010 from 4 US sites were crossmatched with local HIV surveillance registries to identify syphilis case-persons infected with HIV before or shortly after the syphilis diagnosis. We examined HIV VL and CD4 results collected within 6 months before or after syphilis diagnosis for the coinfected cases identified. Independent correlates of detectable VLs (≥200 copies/mL) were determined. RESULTS: We identified 1675 cases of incident primary or secondary syphilis among persons with HIV. Median age was 37 years; 99.5% were men, 41.1% were African American, 24.5% were Hispanics, and 79.9% of the HIV diagnoses were made at least 1 year before syphilis diagnosis. Among those coinfected, there were no VL results reported for 188 (11.2%); of the 1487 (88.8%) with reported VL results, 809 (54.4%) had a detectable VL (median, 25,101 copies/mL; range, 206-3,590,000 copies/mL). Detectable VLs independently correlated with syphilis diagnosed at younger age, at an sexually transmitted disease clinic, and closer in time to HIV diagnosis. CONCLUSIONS: More than half of syphilis case-persons identified with HIV had a detectable VL collected within 6 months of the syphilis diagnosis. This suggests virologic and active behavioral risk for transmitting HIV. |
Validity of the WHO cutoffs for biologically implausible values of weight, height, and BMI in children and adolescents in NHANES from 1999 through 2012
Freedman DS , Lawman HG , Skinner AC , McGuire LC , Allison DB , Ogden CL . Am J Clin Nutr 2015 102 (5) 1000-6 BACKGROUND: The WHO cutoffs to classify biologically implausible values (BIVs) for weight, height, and weight-for-height in children and adolescents are widely used in data cleaning. OBJECTIVES: We assess 1) the prevalence of these BIVs, 2) whether they were consistent with information on waist circumference, arm circumference, and leg lengths, and 3) the effect of their exclusion on the estimated prevalence of obesity in 2- to 19-y-olds in the NHANES, which is a study in which extreme values were verified when recorded. DESIGN: We conducted cross-sectional analyses in 26,480 children and adolescents in the NHANES from 1999-2000 through 2011-2012. RESULTS: The overall prevalence for a BIV for any body-size measure was 0.9% (n = 277), and almost all BIVs were due to extremely high, rather than low, values. Of 186 subjects who had a high BIV for weight or body mass index (BMI), all but one subject had both arm and waist circumferences that were greater than the sex- and age-specific 95th percentiles; 75% of subjects had circumferences greater than the 99th percentile. Of 63 subjects with a high height BIV, 75% of them had a leg length that was greater than the 95th percentile. The exclusion of children and adolescents with a BIV reduced the overall prevalence of obesity by approximately 0.5 percentage points and by 1.7% in non-Hispanic blacks. CONCLUSIONS: Most of the extremely high values of weight, height, and BMI flagged as BIVs in the NHANES are very likely correct. The increase of z score cutoffs or the use of an alternative method to detect possible errors could improve the balance between removing incorrect values and retaining extremely high, but accurate, values in other data sets. |
Novel serologic biomarkers provide accurate estimates of recent Plasmodium falciparum exposure for individuals and communities
Helb DA , Tetteh KK , Felgner PL , Skinner J , Hubbard A , Arinaitwe E , Mayanja-Kizza H , Ssewanyana I , Kamya MR , Beeson JG , Tappero J , Smith DL , Crompton PD , Rosenthal PJ , Dorsey G , Drakeley CJ , Greenhouse B . Proc Natl Acad Sci U S A 2015 112 (32) E4438-47 Tools to reliably measure Plasmodium falciparum (Pf) exposure in individuals and communities are needed to guide and evaluate malaria control interventions. Serologic assays can potentially produce precise exposure estimates at low cost; however, current approaches based on responses to a few characterized antigens are not designed to estimate exposure in individuals. Pf-specific antibody responses differ by antigen, suggesting that selection of antigens with defined kinetic profiles will improve estimates of Pf exposure. To identify novel serologic biomarkers of malaria exposure, we evaluated responses to 856 Pf antigens by protein microarray in 186 Ugandan children, for whom detailed Pf exposure data were available. Using data-adaptive statistical methods, we identified combinations of antibody responses that maximized information on an individual's recent exposure. Responses to three novel Pf antigens accurately classified whether an individual had been infected within the last 30, 90, or 365 d (cross-validated area under the curve = 0.86-0.93), whereas responses to six antigens accurately estimated an individual's malaria incidence in the prior year. Cross-validated incidence predictions for individuals in different communities provided accurate stratification of exposure between populations and suggest that precise estimates of community exposure can be obtained from sampling a small subset of that community. In addition, serologic incidence predictions from cross-sectional samples characterized heterogeneity within a community similarly to 1 y of continuous passive surveillance. Development of simple ELISA-based assays derived from the successful selection strategy outlined here offers the potential to generate rich epidemiologic surveillance data that will be widely accessible to malaria control programs. |
HIV status and viral loads among men testing positive for rectal gonorrhoea and chlamydia, Maricopa County, Arizona, USA, 2011-2013
Taylor M , Newman D , Gonzalez J , Skinner J , Khurana R , Mickey T . HIV Med 2014 16 (4) 249-54 OBJECTIVES: Men diagnosed with rectal gonorrhoea (GC) and chlamydia (CT) have engaged in unprotected receptive anal intercourse. We reviewed the HIV positivity and HIV viral loads (VLs) of men who had rectal GC and CT testing to evaluate potential HIV acquisition and transmission risk. METHODS: Rectal GC and CT testing data for men attending the Maricopa County STD clinic during the period from 1 October 2011 to 30 September 2013 were cross-matched with HIV surveillance data to identify men with HIV coinfection. We examined HIV status, HIV diagnosis date, and the values of VL collected nearest to the date of reported rectal infection. RESULTS: During the 2-year time period, 1591 men were tested for rectal GC and CT. Of the men tested, 506 (31.8%) were positive for GC (13.2%), CT (12.2%) or both (6.4%); 119 (23.5%) of those with rectal GC or CT were coinfected with HIV. Among the 275 men with HIV at the time of rectal testing, 54 (19.6%) had no reported VL; 63 (22.9%) had an undetectable VL (< 20 HIV-1 RNA copies/mL) and 158 (57.4%) had a detectable VL collected within 1 year of rectal diagnosis. Mean VL was higher among HIV and rectal GC/CT coinfected cases compared with men with HIV alone (174 316 vs. 57 717 copies/mL, respectively; P = 0.04). CONCLUSIONS: Approximately one-third of men undergoing rectal testing were positive for GC or CT and one-quarter of men with rectal GC or CT also had HIV infection. Of the HIV-infected men tested for rectal GC or CT, more than half had a detectable VL collected near the time of rectal testing, demonstrating a risk for transmitting HIV. |
Identification and genetic characterization of Clostridium botulinum serotype A strains from commercially pasteurized carrot juice.
Marshall KM , Nowaczyk L 2nd , Raphael BH , Skinner GE , Rukma Reddy N . Food Microbiol 2014 44 149-55 Clostridium botulinum is an important foodborne pathogen capable of forming heat resistant endospores and producing deadly botulinum neurotoxins (BoNTs). In 2006, C. botulinum was responsible for an international outbreak of botulism attributed to the consumption of commercially pasteurized carrot juice. The purpose of this study was to isolate and characterize strains of C. botulinum from the adulterated product. Carrot juice bottles retrieved from the manufacturing facility were analyzed for the presence of BoNT and BoNT-producing isolates using DIG-ELISA. Toxigenic isolates from the carrot juice were analyzed using pulsed-field gel electrophoresis (PFGE) and DNA microarray analysis to determine their genetic relatedness to the original outbreak strains CDC51348 and CDC51303. PFGE revealed that isolates CJ4-1 and CJ10-1 shared an identical pulsotype with strain CDC51303, whereas isolate CJ5-1 displayed a unique restriction banding pattern. DNA microarray analysis identified several phage related genes unique to strain CJ5-1, and Southern hybridization analysis of XhoI digested and nondigested DNA showed their chromosomal location, while a homolog to pCLI_A009 of plasmid pCLI of C. botulinum serotype Langeland F, was located on a small plasmid. The acquisition or loss of bacteriophages and other mobile genetic elements among C. botulinum strains has epidemiological and evolutionary implications. |
The national haemophilia program standards, evaluation and oversight systems in the United States of America
Skinner MW , Soucie JM , McLaughlin K . Blood Transfus 2014 12 Suppl 3 e542-8 The US National Hemophilia Program (NHP) is a collaborative relationship between the Maternal and Child Health Bureau (MCHB) of the Health Resources and Services Administration (HRSA), the Centers for Disease Control and Prevention (CDC) and the Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation (NHF). This article is written in three parts outlining the roles, collaborative and integrated working relationships of the three core entities (MCHB, CDC, NHF). We will discuss the birth and evolution of the modern day NHP and haemophilia treatment center (HTC) network, the evolution and role of surveillance programs, treatment guideline and standard setting, the impact of health care reform on access to comprehensive care and on-going initiatives to improve health outcomes for those living with haemophilia and related bleeding disorders. | Although there is, at present, no formal HTC accreditation system in the US, we will describe a number of programs and systems that are already in place to promote and measure adherence to best practices, monitor patient outcomes and encourage continual operational and clinical improvement according to established standards. Finally, we will describe various initiatives that are underway to further develop evidence-based guidelines, which may lay the foundation for a future, formalised HTC self-audit evaluation or accreditation system. |
Viral loads among young HIV-infected men with early syphilis
Taylor MM , Li WY , Skinner J , Mickey T . J Int Assoc Provid AIDS Care 2014 13 (6) 501-5 High rates of HIV coinfection among men with syphilis suggest HIV transmission opportunities due to biologic and behavioral risk synergy. We abstracted HIV viral loads for HIV-infected males aged 24 years or younger with a diagnosis of early syphilis (ES) in Maricopa County, Arizona, in order to evaluate HIV infectivity. During 2009 to 2012, there were 56 HIV-infected, ES cases meeting the age criteria, of whom 32 (57%) had a detectable viral load performed within 1 year of syphilis diagnosis (median 21 000 copies/mL, range 130-302 844 copies/mL). Only 4 (7%) of the 56 patients had an undetectable viral load (<100 copies/mL) reported within a year of syphilis diagnosis. Twenty (36%) had no reported viral load or a viral load collected after 1 year of syphilis diagnosis. Among this group of young men coinfected with HIV and ES, many had detectable viral loads collected near the time of syphilis diagnosis, suggesting the potential for HIV transmission. |
Natural infection of Burkholderia pseudomallei in an imported pigtail macaque (Macaca nemestrina) and management of the exposed colony
Johnson CH , Skinner BL , Dietz SM , Blaney D , Engel RM , Lathrop GW , Hoffmaster AR , Gee JE , Elrod MG , Powell N , Walke H . Comp Med 2013 63 (6) 528-35 Identification of the select agent Burkholderia pseudomallei in macaques imported into the United States is rare. A purpose-bred, 4.5-y-old pigtail macaque (Macaca nemestrina) imported from Southeast Asia was received from a commercial vendor at our facility in March 2012. After the initial acclimation period of 5 to 7 d, physical examination of the macaque revealed a subcutaneous abscess that surrounded the right stifle joint. The wound was treated and resolved over 3 mo. In August 2012, 2 mo after the stifle joint wound resolved, the macaque exhibited neurologic clinical signs. Postmortem microbiologic analysis revealed that the macaque was infected with B. pseudomallei. This case report describes the clinical evaluation of a B. pseudomallei-infected macaque, management and care of the potentially exposed colony of animals, and protocols established for the animal care staff that worked with the infected macaque and potentially exposed colony. This article also provides relevant information on addressing matters related to regulatory issues and risk management of potentially exposed animals and animal care staff. |
Trends in reported syphilis and gonorrhea among HIV-infected people in Arizona: implications for prevention and control
Skinner JM , Distefano J , Warrington J , Bailey SR , Winscott M , Taylor MM . Public Health Rep 2014 129 85-94 OBJECTIVE: HIV and sexually transmitted disease (STD) surveillance patterns in Arizona suggested the need for integrated data analyses to identify trends. METHODS: We compiled all HIV/AIDS cases diagnosed from 1998 to 2008 that were reported in Arizona and syphilis or gonorrhea cases diagnosed from 1998 to 2008 in Arizona. We used deterministic matching to identify individuals who were diagnosed with HIV and one or more STDs, and calculated time intervals between diagnoses. RESULTS: Of 23,940 people with HIV/AIDS reported from 1998 to 2008, 1,899 (2.6%) had at least one syphilis or gonorrhea diagnosis from 1998 to 2008. Approximately 85% of these cases reported male-to-male sexual contact. Among males with syphilis, HIV coinfection increased from 0.5% in 1998 to 29.1% in 2008. Among males with gonorrhea, HIV coinfection increased from 2.0% in 1998 to 3.1% in 2008. Among HIV cases diagnosed from 2004 to 2008 and reported with at least one syphilis or gonorrhea diagnosis, the majority of syphilis cases (76.1%) were diagnosed at or after HIV diagnosis, whereas a majority of gonorrhea cases (54.9%) were diagnosed prior to HIV diagnosis. CONCLUSION: Use of the deterministic matching method identified increases in STD infections among HIV-infected people. The routine performance of this cross-matching method may be a useful tool in identifying these high-risk individuals so that targeted partner services and appropriate care referrals may be used in a timely fashion. |
Gonorrhea infections diagnosed among persons living with HIV/AIDS: identifying opportunities for integrated prevention services in New York City, Washington, DC, Miami/Dade County, and Arizona
Taylor MM , Schillinger JA , Furness BW , Brewer T , Newman DR , Pathela P , Skinner J , Braunstein S , Shepard C , Ahmed T , Griffin A , Blank S , Peterman TA . J Acquir Immune Defic Syndr 2013 64 (1) 115-20 Persons living with HIV/AIDS who acquire new sexually transmitted diseases (STDs) pose a risk for enhanced transmission of both HIV and STDs. To describe the frequency of HIV coinfection among gonorrhea cases (GC), HIV and GC surveillance databases (2000-2008) were cross-matched in New York City (NYC), Washington, DC (DC), Miami/Dade County (MDC), and Arizona (AZ). During 2000-2008, 4.6% (9471/205,689) of reported GCs occurred among persons with previously diagnosed HIV: NYC (5.5%), DC (7.3%), MDC (4%), and AZ (2%). The overall HIV-GC coinfection rates increased over the study period in all 4 sites. Real-time data integration could allow for enhanced prevention among persons with HIV infection and acute STDs. |
Prophage induction is enhanced and required for renal disease and lethality in an EHEC mouse model
Tyler JS , Beeri K , Reynolds JL , Alteri CJ , Skinner KG , Friedman JH , Eaton KA , Friedman DI . PLoS Pathog 2013 9 (3) e1003236 Enterohemorrhagic Escherichia coli (EHEC), particularly serotype O157:H7, causes hemorrhagic colitis, hemolytic uremic syndrome, and even death. In vitro studies showed that Shiga toxin 2 (Stx2), the primary virulence factor expressed by EDL933 (an O157:H7 strain), is encoded by the 933W prophage. And the bacterial subpopulation in which the 933W prophage is induced is the producer of Stx2. Using the germ-free mouse, we show the essential role 933W induction plays in the virulence of EDL933 infection. An EDL933 derivative with a single mutation in its 933W prophage, resulting specifically in that phage being uninducible, colonizes the intestines, but fails to cause any of the pathological changes seen with the parent strain. Hence, induction of the 933W prophage is the primary event leading to disease from EDL933 infection. We constructed a derivative of EDL933, SIVET, with a biosensor that specifically measures induction of the 933W prophage. Using this biosensor to measure 933W induction in germ-free mice, we found an increase three logs greater than was expected from in vitro results. Since the induced population produces and releases Stx2, this result indicates that an activity in the intestine increases Stx2 production. |
HIV-1 protease inhibitors and clinical malaria: a secondary analysis of the AIDS Clinical Trials Group A5208 study
Porter KA , Cole SR , Eron JJ Jr , Zheng Y , Hughes MD , Lockman S , Poole C , Skinner-Adams TS , Hosseinipour M , Shaffer D , D'Amico R , Sawe FK , Siika A , Stringer E , Currier JS , Chipato T , Salata R , McCarthy JS , Meshnick SR . Antimicrob Agents Chemother 2012 56 (2) 995-1000 HIV-1 protease inhibitors (PIs) have antimalarial activity in vitro and in murine models. The potential beneficial effect of HIV-1 PIs on malaria has not been studied in clinical settings. We used data from Adult AIDS Clinical Trials Group A5208 sites where malaria is endemic to compare the incidence of clinically diagnosed malaria among HIV-infected adult women randomized to either lopinavir/ritonavir (LPV/r)-based antiretroviral therapy (ART) or to nevirapine (NVP)-based ART. We calculated hazard ratios and 95% confidence intervals. We conducted a recurrent events analysis that included both first and second clinical malarial episodes and also conducted analyses to assess the sensitivity of results to outcome misclassification. Among the 445 women in this analysis, 137 (31%) received a clinical diagnosis of malaria at least once during follow-up. Of these 137, 72 (53%) were randomized to LPV/r-based ART. Assignment to the LPV/r treatment group (n = 226) was not consistent with a large decrease in the hazard of first clinical malarial episode (hazard ratio = 1.11 [0.79 to 1.56]). The results were similar in the recurrent events analysis. Sensitivity analyses indicated the results were robust to reasonable levels of outcome misclassification. In this study, the treatment with LPV/r compared to NVP had no apparent beneficial effect on the incidence of clinical malaria among HIV-infected adult women. Additional research concerning the effects of PI-based therapy on the incidence of malaria diagnosed by more specific criteria and among groups at a higher risk for severe disease is warranted. |
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