Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 75 Records) |
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Association between per- and polyfluoroalkyl substances exposure and thyroid function biomarkers among females attending a fertility clinic
Zhang Y , Mustieles V , Korevaar TIM , Martin L , Sun Y , Bibi Z , Torres N , Coburn-Sanderson A , First O , Souter I , Petrozza JC , Broeren MAC , Botelho JC , Calafat AM , Wang YX , Messerlian C . Environ Pollut 2024 123513 Per- and polyfluoroalkyl substances (PFAS) exposure was associated with changes in thyroid function in pregnant mothers and the general population. Limited such evidence exists in other susceptible populations such as females with fertility problems. This cross-sectional study included 287 females seeking medically assisted reproduction at a fertility clinic in Massachusetts, United States, between 2005 and 2019. Six long-alkyl chain PFAS, thyroid hormones, and autoimmune antibodies were quantified in baseline serum samples. We used generalized linear models and quantile g-computation to evaluate associations of individual PFAS and their total mixture with thyroid biomarkers. Most females were White individuals (82.7%), had graduate degrees (57.8%), and nearly half had unexplained subfertility (45.9%). Serum concentrations of all examined PFAS and their mixture were significantly associated with 2.6%-5.6% lower total triiodothyronine (TT3) concentrations. Serum concentrations of perfluorononanoate (PFNA), perfluorodecanoate (PFDA), and perfluoroundecanoate (PFUnDA), and of the total mixture were associated with higher ratios of free thyroxine (FT4) to free triiodothyronine (FT3). No associations were found for PFAS and TSH or autoimmune antibodies. Our findings support the thyroid-disrupting effect of long alkyl-chain PFAS among a vulnerable population of subfertile females. |
Characterization of a monoclonal antibody specific to California serogroup orthobunyaviruses and development as a chimeric immunoglobulin M-positive control in human diagnostics
Powers JA , Boroughs KL , Mikula S , Goodman CH , Davis EH , Thrasher EM , Hughes HR , Biggerstaff BJ , Calvert AE . Microbiol Spectr 2023 11 (5) e0196623 California serogroup viruses (CSGVs) of medical importance in the United States include La Crosse virus, Jamestown Canyon virus (JCV), California encephalitis virus, and snowshoe hare virus. Current diagnosis of CSGVs relies heavily on serologic techniques for detecting immunoglobulin M (IgM), an indication of a recent CSGV infection. However, human-positive control sera reactive to viruses in the serogroup are scarce because detection of recent infections is rare. Here, we describe the development of new murine monoclonal antibodies (MAbs) reactive to CSGVs and the engineering of a human-murine chimeric antibody by combining the variable regions of the broadly CSGV cross-reactive murine MAb, 3-3B6/2-3B2 and the constant region of the human IgM. MAb 3-3B6/2-3B2 recognizes a tertiary epitope on the Gn/Gc heterodimer, and epitopes important in JCV neutralization were mapped to the Gc glycoprotein. This engineered human IgM constitutively expressed in a HEK-293 stable cell line can replace human-positive control sera in diagnostic serological techniques such as IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA). Compared to the parent murine MAbs, the human-chimeric IgM antibody had identical serological activity to CSGVs in ELISA and demonstrated equivalent reactivity compared to human immune sera in the MAC-ELISA.IMPORTANCEOrthobunyaviruses in the California serogroup cause severe neurological disease in children and adults. While these viruses are known to circulate widely in North America, their occurrence is rare. Serological testing for CSGVs is hindered by the limited availability and volumes of human-positive specimens needed as controls in serologic assays. Here, we described the development of a murine monoclonal antibody cross-reactive to CSGVs engineered to contain the variable regions of the murine antibody on the backbone of human IgM. The chimeric IgM produced from the stably expressing HEK293 cell line was evaluated for use as a surrogate human-positive control in a serologic diagnostic test. |
Comprehensive evaluation of differential serodiagnosis between Zika and dengue viral infection (preprint)
Chao DY , Whitney MT , Davis BS , Medina FA , Munoz JL , Chang GJ . bioRxiv 2018 421628 Diagnostic testing for Zika virus (ZIKV) or dengue virus (DENV) infection can be accomplished by a nucleic acid detection method; however, a negative result does not exclude infection due to the low virus titer during infection depending on the timing of sample collection. Therefore, a ZIKV- or DENV-specific serological assay is essential for the accurate diagnosis of patients and to prevent potential severe health outcomes. A retrospective study design with dual approaches of collecting human serum samples for testing was developed. All serum samples were extensively evaluated by using both non-infectious virus-like particles (VLPs) and soluble non-structural protein 1 (NS1) in the standard immunoglobulin M (IgM) antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). Both VLP- and NS1-MAC-ELISAs were found to have similar sensitivity for detecting anti-premembrane/envelope and NS1 antibodies from ZIKV-infected patient sera. Group cross reactive (GR)-antibody-ablated homologous fusion peptide-mutated (FP)-VLPs consistently showed higher P/N values than homologous wild-type VLPs. Therefore, FP-VLPs were used to develop the algorithm for differentiating ZIKV from DENV infection. Overall, the sensitivity and specificity of the FP-VLP-MAC-ELISA and the NS1-MAC-ELISA were each higher than 80% with no statistical significance. A novel approach to differentiate ZIKV from DENV infection serologically has been developed. The accuracy can reach up to 95% when combining both VLP and NS1 assays. In comparison to current guidelines using neutralization tests to measure ZIKV antibody, this approach can facilitate laboratory screening for ZIKV infection, especially in regions where DENV infection is endemic and capacity for neutralization testing does not exist. |
Vaccine effectiveness of CanSino (Adv5-nCoV) COVID-19 vaccine among childcare workers - Mexico, March-December 2021 (preprint)
Richardson VL , Franco MAC , Marquez AB , Valdez LM , Ceronio LEC , Cruz VC , Gharpure R , Lafond KE , Yau TS , Azziz-Baumgartner E , Avila MH . medRxiv 2022 17 Background: Beginning in March 2021, Mexico vaccinated childcare workers with a single-dose CanSino Biologics (Adv5-nCoV) COVID-19 vaccine. Although CanSino is currently approved for use in 10 Latin American, Asian, and European countries, little information is available about its vaccine effectiveness (VE). Method(s): We evaluated CanSino VE within a childcare worker cohort that included 1,408 childcare facilities. Participants were followed during March-December 2021 and tested through SARS-CoV-2 RT-PCR or rapid antigen test if they developed any symptom compatible with COVID-19. Vaccination status was obtained through worker registries. VE was calculated as 100% x (1-hazard ratio for SARS-CoV-2 infection in fully vaccinated vs. unvaccinated participants), using an Andersen-Gill model adjusted for age, sex, state, and local viral circulation. Result(s): The cohort included 43,925 persons who were mostly (96%) female with a median age of 32 years; 37,646 (86%) were vaccinated with CanSino. During March-December 2021, 2,250 (5%) participants had laboratory-confirmed COVID-19, of whom 25 were hospitalized and 6 died. Adjusted VE was 20% (95% CI = 10-29%) against illness, 76% (42-90%) against hospitalization, and 94% (66-99%) against death. VE against illness declined from 48% (95% CI = 33-61) after 14-60 days following full vaccination to 20% (95% CI = 9-31) after 61-120 days. Conclusion(s): CanSino vaccine was effective at preventing COVID-19 illness and highly effective at preventing hospitalization and death. It will be useful to further evaluate duration of protection and assess the value of booster doses to prevent COVID-19 and severe outcomes. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Notes from the Field: Legionnaires disease in a U.S. traveler after staying in a private vacation rental house in the U.S. Virgin Islands - United States, February 2022
Mac VV , Labgold K , Moline HL , Smith JC , Carroll J , Clemmons N , Edens C , Ellis B , Harrison C , Henderson KC , Ishaq MK , Kozak-Muiznieks NA , Kunz J , Lawrence M , Lucas CE , Walker HL , Willby MJ , Ellis EM . MMWR Morb Mortal Wkly Rep 2023 72 (20) 564-565 On February 1, 2022, the U.S. Virgin Islands (USVI) Department of Health (VIDOH) was notified of a confirmed case of Legionnaires disease in an adult U.S. resident (Figure). The patient, a man aged 55 years, returned to his U.S. state of residence from leisure travel in USVI on January 22 and developed a cough, shortness of breath, and fatigue on January 23. On January 29, he was hospitalized for shortness of breath and received a positive SARS-CoV-2 test result at admission. The combination of the patient’s symptoms and recent travel history prompted administration of a urinary antigen test (UAT) for Legionnaires disease specific to Legionella pneumophila serogroup 1 (Lp1); a positive result was returned on January 31. Inpatient treatment administered for COVID-19 pneumonia and Legionnaires disease included remdesivir, oral levofloxacin, oral and intravenous steroid therapy, and as-needed use of a bronchodilator inhaler and an expectorant. Remdesivir was discontinued during inpatient treatment because of elevated liver enzymes. The patient recovered and was discharged on February 2. |
Notes from the field: Prevalence of previous dengue virus infection among children and adolescents - U.S. Virgin Islands, 2022
Mac VV , Wong JM , Volkman HR , Perez-Padilla J , Wakeman B , Delorey M , Biggerstaff BJ , Fagre A , Gumbs A , Drummond A , Zimmerman B , Lettsome B , Medina FA , Paz-Bailey G , Lawrence M , Ellis B , Rosenblum HG , Carroll J , Roth J , Rossington J , Meeker JR , Joseph J , Janssen J , Ekpo LL , Carrillo M , Hernandez N , Charles P , Tosado R , Soto R , Battle S , Bart SM , Wanga V , Valentin W , Powell W , Battiste Z , Ellis EM , Adams LE . MMWR Morb Mortal Wkly Rep 2023 72 (11) 288-289 In May 2019, the Food and Drug Administration issued approval for Dengvaxia (Sanofi Pasteur), a live-attenuated, chimeric tetravalent dengue vaccine (1). In June 2021, the Advisory Committee on Immunization Practices (ACIP) recommended vaccination with Dengvaxia for children and adolescents aged 9–16 years with laboratory confirmation of previous dengue virus infection and who live in areas with endemic dengue transmission, such as the U.S. Virgin Islands (USVI)† (2). Confirming previous dengue virus infection before vaccine administration (prevaccination screening) is important because 1) although Dengvaxia decreases hospitalization and severe disease from dengue among persons with a previous infection, it increases the risk for these outcomes among persons without a previous infection; 2) many dengue virus infections are asymptomatic; and 3) many patients with symptomatic infections do not seek medical attention or receive appropriate testing (3). Sufficient laboratory evidence of previous dengue virus infection includes a history of laboratory-confirmed dengue§ or a positive serologic test result that meets ACIP-recommended performance standards for prevaccination screening, defined as high specificity (≥98%) and sensitivity (≥75%). A seroprevalence of 20% in the vaccine-eligible population (corresponding to a positive predictive value of ≥90% for a test with minimum sensitivity of 75% and minimum specificity of 98%) is recommended to maximize vaccine safety and minimize the risk for vaccinating persons without a previous dengue virus infection (2). |
A qualitative evaluation and conceptual framework on the use of the Birth weight and Age-at-death Boxes for Intervention and Evaluation System (BABIES) matrix for perinatal health in Uganda
Dynes MM , Daniel GA , Mac V , Picho B , Asiimwe A , Nalutaaya A , Opio G , Kamara V , Kaharuza F , Serbanescu F . BMC Pregnancy Childbirth 2023 23 (1) 86 BACKGROUND: Perinatal mortality (newborn deaths in the first week of life and stillbirths) continues to be a significant global health threat, particularly in resource-constrained settings. Low-tech, innovative solutions that close the quality-of-care gap may contribute to progress toward the Sustainable Development Goals for health by 2030. From 2012 to 2018, the Saving Mothers, Giving Life Initiative (SMGL) implemented the Birth weight and Age-at-Death Boxes for Intervention and Evaluation System (BABIES) matrix in Western Uganda. The BABIES matrix provides a simple, standardized way to track perinatal health outcomes to inform evidence-based quality improvement strategies. METHODS: In November 2017, a facility-based qualitative evaluation was conducted using in-depth interviews with 29 health workers in 16 health facilities implementing BABIES in Uganda. Data were analyzed using directed content analysis across five domains: 1) perceived ease of use, 2) how the matrix was used, 3) changes in behavior or standard operating procedures after introduction, 4) perceived value of the matrix, and 5) program sustainability. RESULTS: Values in the matrix were easy to calculate, but training was required to ensure correct data placement and interpretation. Displaying the matrix on a highly visible board in the maternity ward fostered a sense of accountability for health outcomes. BABIES matrix reports were compiled, reviewed, and responded to monthly by interprofessional teams, prompting collaboration across units to fill data gaps and support perinatal death reviews. Respondents reported improved staff communication and performance appraisal, community engagement, and ability to track and link clinical outcomes with actions. Midwives felt empowered to participate in the problem-solving process. Respondents were motivated to continue using BABIES, although sustainability concerns were raised due to funding and staff shortages. CONCLUSIONS: District-level health systems can use data compiled from the BABIES matrix to inform policy and guide implementation of community-centered health practices to improve perinatal heath. Future work may consider using the Conceptual Framework on Use of the BABIES Matrix for Perinatal Health as a model to operationalize concepts and test the impact of the tool over time. |
Vaccine effectiveness of CanSino (Adv5-nCoV) COVID-19 vaccine among childcare workers - Mexico, March-December 2021.
Richardson VL , Franco MAC , Márquez AB , Valdez LM , Ceronio LEC , Cruz VC , Gharpure R , Lafond KE , Yau TS , Azziz-Baumgartner E , Ávila MH . Clin Infect Dis 2022 75 S167-S173 BACKGROUND: Beginning in March 2021, Mexico vaccinated childcare workers with a single-dose CanSino Biologics (Adv5-nCoV) COVID-19 vaccine. Although CanSino is currently approved for use in 10 Latin American, Asian, and European countries, little information is available about its vaccine effectiveness (VE). METHODS: We evaluated CanSino VE within a childcare worker cohort that included 1,408 childcare facilities. Participants were followed during March-December 2021 and tested through SARS-CoV-2 RT-PCR or rapid antigen test if they developed any symptom compatible with COVID-19. Vaccination status was obtained through worker registries. VE was calculated as 100% × (1-hazard ratio for SARS-CoV-2 infection in fully vaccinated vs. unvaccinated participants), using an Andersen-Gill model adjusted for age, sex, state, and local viral circulation. RESULTS: The cohort included 43,925 persons who were mostly (96%) female with a median age of 32 years; 37,646 (86%) were vaccinated with CanSino. During March-December 2021, 2,250 (5%) participants had laboratory-confirmed COVID-19, of whom 25 were hospitalized and 6 died. Adjusted VE was 20% (95% CI = 10-29%) against illness, 76% (42-90%) against hospitalization, and 94% (66-99%) against death. VE against illness declined from 48% (95% CI = 33-61) after 14-60 days following full vaccination to 20% (95% CI = 9-31) after 61-120 days. CONCLUSIONS: CanSino vaccine was effective at preventing COVID-19 illness and highly effective at preventing hospitalization and death. It will be useful to further evaluate duration of protection and assess the value of booster doses to prevent COVID-19 and severe outcomes. |
Risk factors for infection with chikungunya and Zika viruses in southern Puerto Rico: A community-based cross-sectional seroprevalence survey
Adams LE , Sánchez-González L , Rodriguez DM , Ryff K , Major C , Lorenzi O , Delorey M , Medina FA , Muñoz-Jordán JL , Brown G , Ortiz M , Waterman SH , Rivera-Amill V , Paz-Bailey G . PLoS Negl Trop Dis 2022 16 (6) e0010416 Chikungunya virus (CHIKV) caused a large outbreak in Puerto Rico in 2014, followed by a Zika virus (ZIKV) outbreak in 2016. Communities Organized for the Prevention of Arboviruses (COPA) is a cohort study in southern Puerto Rico, initiated in 2018 to measure arboviral disease risk and provide a platform to evaluate interventions. To identify risk factors for infection, we assessed prevalence of previous CHIKV infection and recent ZIKV and DENV infection in a cross-sectional study among COPA participants. Participants aged 1-50 years (y) were recruited from randomly selected households in study clusters. Each participant completed an interview and provided a blood specimen, which was tested by anti-CHIKV IgG ELISA assay and anti-ZIKV and anti-DENV IgM MAC-ELISA assays. We assessed individual, household, and community factors associated with a positive result for CHIKV or ZIKV after adjusting for confounders. During 2018-2019, 4,090 participants were enrolled; 61% were female and median age was 28y (interquartile range [IQR]: 16-41). Among 4,035 participants tested for CHIKV, 1,268 (31.4%) had evidence of previous infection. CHIKV infection prevalence was lower among children 1-10 years old compared to people 11 and older (adjusted odds ratio [aOR] 2.30; 95% CI 1.71-3.08). Lower CHIKV infection prevalence was associated with home screens (aOR 0.51; 95% CI 0.42-0.61) and air conditioning (aOR 0.64; 95% CI 0.54-0.77). CHIKV infection prevalence also varied by study cluster of residence and insurance type. Few participants (16; 0.4%) had evidence of recent DENV infection by IgM. Among 4,035 participants tested for ZIKV, 651 (16%) had evidence of recent infection. Infection prevalence increased with older age, from 7% among 1-10y olds up to 19% among 41-50y olds (aOR 3.23; 95% CI 2.16-4.84). Males had an increased risk of Zika infection prevalence compared with females (aOR 1.31; 95% CI 1.09-1.57). ZIKV infection prevalence also decreased with the presence of home screens (aOR 0.66; 95% CI 0.54-0.82) and air conditioning (aOR 0.69; 95% CI 0.57-0.84). Similar infection patterns were observed for recent ZIKV infection prevalence and previous CHIKV infection prevalence by age, and the presence of screens and air conditioners in the home decreased infection risk from both viruses by as much as 50%. |
Capacity of a multiplex IgM antibody capture ELISA to differentiate Zika and dengue virus infections in areas of concurrent endemic transmission
Medina FA , Vila F , Premkumar L , Lorenzi O , Paz-Bailey G , Alvarado LI , Rivera-Amill V , de Silva A , Waterman S , Muñoz-Jordán J . Am J Trop Med Hyg 2021 106 (2) 585-592 Serological cross-reactivity has proved to be a challenge to diagnose Zika virus (ZIKV) infections in dengue virus (DENV) endemic countries. Confirmatory testing of ZIKV IgM positive results by plaque reduction neutralization tests (PRNTs) provides clarification in only a minority of cases because most individuals infected with ZIKV were previously exposed to DENV. The goal of this study was to evaluate the performance of a ZIKV/DENV DUO IgM antibody capture ELISA (MAC-ELISA) for discriminating between DENV and ZIKV infections in endemic regions. Our performance evaluation included acute and convalescent specimens from patients with real-time reverse transcription polymerase chain reaction (RT-PCR)-confirmed DENV or ZIKV from the Sentinel Enhanced Dengue Surveillance System in Ponce, Puerto Rico. The ZIKV/DENV DUO MAC-ELISA specificity was 100% for DENV (N = 127) and 98.4% for ZIKV (N = 275) when specimens were tested during the optimal testing window (days post-onset of illness [DPO] 6-120). The ZIKV/DENV DUO MAC-ELISA sensitivity of RT-PCR confirmed specimens reached 100% for DENV by DPO 6 and for ZIKV by DPO 9. Our new ZIKV/DENV DUO MAC-ELISA was also able to distinguish ZIKV and DENV regardless of previous DENV exposure. We conclude this novel serologic diagnostic assay can accurately discriminate ZIKV and DENV infections. This can potentially be useful considering that the more labor-intensive and expensive PRNT assay may not be an option for confirmatory diagnosis in areas that lack PRNT capacity, but experience circulation of both DENV and ZIKV. |
Delayed lactose utilization among Shiga toxin-producing Escherichia coli of serogroup O121.
Gill A , McMahon T , Dussault F , Jinneman K , Lindsey R , Martin H , Stoneburg D , Strockbine N , Wetherington J , Feng P . Food Microbiol 2022 102 103903 Two outbreaks of Shiga toxin-producing Escherichia coli O121:H19 associated with wheat flour, in the United States of America and Canada, involved strains with an unusual phenotype, delayed lactose utilization (DLU). These strains do not ferment lactose when initially cultured on MacConkey agar (MAC), but lactose fermentation occurs following subculture to a second plate of MAC. The prevalence of DLU was determined by examining the -galactosidase activity of 49 strains of E. coli O121, and of 37 other strains of E. coli. Twenty four of forty three O121:H19 and one O121:NM displayed DLU. Two strains (O121:NM and O145:H34) did not have detectable -galactosidase activity. -glucuronidase activity of O121 strains was also determined. All but six DLU strains had normal -glucuronidase activity. -glucuronidase activity was suppressed on MAC for 17 of 23 O121 non-DLU strains. Genomic analysis found that DLU strains possessed an insertion sequence, IS600 (1267 bp), between lacZ (-galactosidase) and lacY (-galactoside permease), that was not present in strains exhibiting normal lactose utilization. The insert might reduce the expression of -galactoside permease, delaying import of lactose, resulting in the DLU phenotype. The high probability of DLU should be considered when using lactose-containing media for the isolation of STEC O121. 2021 |
A Longitudinal Model-Based Biomarker Analysis of Exposure Response in Adults with Pulmonary Tuberculosis
Gewitz AD , Solans BP , Mac Kenzie WR , Heilig C , Whitworth WC , Johnson JL , Nsubuga P , Dorman S , Weiner M , Savic RM . Antimicrob Agents Chemother 2021 65 (10) Aac0179420 The identification of sensitive, specific and reliable biomarkers that can be quantified in the early phases of tuberculosis treatment and predictive of long-term outcome is key for the development of an effective short-course treatment regimen. Time-to-positivity (TTP), a biomarker of treatment outcome against Mycobacterium tuberculosis, measures longitudinal bacterial growth in Mycobacteria Growth Indicator Tube broth culture and may be predictive of standard time-to-stable-culture-conversion (TSCC). In two randomized phase 2b trials investigating dose-ranging rifapentine (Study 29 and 29x), 662 participants had sputum collected over six months where TTP, TSCC and time-to-culture-conversion were quantified. The goals of this post hoc study were to characterize longitudinal TTP profiles and to identify individual patient characteristics associated with delayed time to culture conversion. In order to do so, a nonlinear mixed-effects model describing longitudinal TTP was built. Independent variables associated with increased bacterial clearance (increased TTP), assessed by subject-specific and population-level trajectories, were higher rifapentine exposure, lower baseline grade of sputum acid-fast bacilli smear, absence of productive cough, and lower extent of lung infiltrates on radiographs. Importantly, sensitivity analysis revealed that major learning milestones in phase 2b trials, such as significant exposure-response and covariate relationships, could be detected using truncated TTP data as early as 6 weeks from start of treatment, suggesting alternative phase 2B study designs. The TTP model built depicts a novel phase 2B surrogate endpoint that can inform early assessment of experimental treatment efficacy and treatment failure or relapse in patients treated with shorter and novel TB treatment regimens, improving efficiency of phase 2 clinical trials. |
Underlying Medical Conditions and Severe Illness Among 540,667 Adults Hospitalized With COVID-19, March 2020-March 2021.
Kompaniyets L , Pennington AF , Goodman AB , Rosenblum HG , Belay B , Ko JY , Chevinsky JR , Schieber LZ , Summers AD , Lavery AM , Preston LE , Danielson ML , Cui Z , Namulanda G , Yusuf H , Mac Kenzie WR , Wong KK , Baggs J , Boehmer TK , Gundlapalli AV . Prev Chronic Dis 2021 18 E66 INTRODUCTION: Severe COVID-19 illness in adults has been linked to underlying medical conditions. This study identified frequent underlying conditions and their attributable risk of severe COVID-19 illness. METHODS: We used data from more than 800 US hospitals in the Premier Healthcare Database Special COVID-19 Release (PHD-SR) to describe hospitalized patients aged 18 years or older with COVID-19 from March 2020 through March 2021. We used multivariable generalized linear models to estimate adjusted risk of intensive care unit admission, invasive mechanical ventilation, and death associated with frequent conditions and total number of conditions. RESULTS: Among 4,899,447 hospitalized adults in PHD-SR, 540,667 (11.0%) were patients with COVID-19, of whom 94.9% had at least 1 underlying medical condition. Essential hypertension (50.4%), disorders of lipid metabolism (49.4%), and obesity (33.0%) were the most common. The strongest risk factors for death were obesity (adjusted risk ratio [aRR] = 1.30; 95% CI, 1.27-1.33), anxiety and fear-related disorders (aRR = 1.28; 95% CI, 1.25-1.31), and diabetes with complication (aRR = 1.26; 95% CI, 1.24-1.28), as well as the total number of conditions, with aRRs of death ranging from 1.53 (95% CI, 1.41-1.67) for patients with 1 condition to 3.82 (95% CI, 3.45-4.23) for patients with more than 10 conditions (compared with patients with no conditions). CONCLUSION: Certain underlying conditions and the number of conditions were associated with severe COVID-19 illness. Hypertension and disorders of lipid metabolism were the most frequent, whereas obesity, diabetes with complication, and anxiety disorders were the strongest risk factors for severe COVID-19 illness. Careful evaluation and management of underlying conditions among patients with COVID-19 can help stratify risk for severe illness. |
Underlying Medical Conditions Associated With Severe COVID-19 Illness Among Children.
Kompaniyets L , Agathis NT , Nelson JM , Preston LE , Ko JY , Belay B , Pennington AF , Danielson ML , DeSisto CL , Chevinsky JR , Schieber LZ , Yusuf H , Baggs J , Mac Kenzie WR , Wong KK , Boehmer TK , Gundlapalli AV , Goodman AB . JAMA Netw Open 2021 4 (6) e2111182 IMPORTANCE: Information on underlying conditions and severe COVID-19 illness among children is limited. OBJECTIVE: To examine the risk of severe COVID-19 illness among children associated with underlying medical conditions and medical complexity. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included patients aged 18 years and younger with International Statistical Classification of Diseases, Tenth Revision, Clinical Modification code U07.1 (COVID-19) or B97.29 (other coronavirus) during an emergency department or inpatient encounter from March 2020 through January 2021. Data were collected from the Premier Healthcare Database Special COVID-19 Release, which included data from more than 800 US hospitals. Multivariable generalized linear models, controlling for patient and hospital characteristics, were used to estimate adjusted risk of severe COVID-19 illness associated with underlying medical conditions and medical complexity. EXPOSURES: Underlying medical conditions and medical complexity (ie, presence of complex or noncomplex chronic disease). MAIN OUTCOMES AND MEASURES: Hospitalization and severe illness when hospitalized (ie, combined outcome of intensive care unit admission, invasive mechanical ventilation, or death). RESULTS: Among 43 465 patients with COVID-19 aged 18 years or younger, the median (interquartile range) age was 12 (4-16) years, 22 943 (52.8%) were female patients, and 12 491 (28.7%) had underlying medical conditions. The most common diagnosed conditions were asthma (4416 [10.2%]), neurodevelopmental disorders (1690 [3.9%]), anxiety and fear-related disorders (1374 [3.2%]), depressive disorders (1209 [2.8%]), and obesity (1071 [2.5%]). The strongest risk factors for hospitalization were type 1 diabetes (adjusted risk ratio [aRR], 4.60; 95% CI, 3.91-5.42) and obesity (aRR, 3.07; 95% CI, 2.66-3.54), and the strongest risk factors for severe COVID-19 illness were type 1 diabetes (aRR, 2.38; 95% CI, 2.06-2.76) and cardiac and circulatory congenital anomalies (aRR, 1.72; 95% CI, 1.48-1.99). Prematurity was a risk factor for severe COVID-19 illness among children younger than 2 years (aRR, 1.83; 95% CI, 1.47-2.29). Chronic and complex chronic disease were risk factors for hospitalization, with aRRs of 2.91 (95% CI, 2.63-3.23) and 7.86 (95% CI, 6.91-8.95), respectively, as well as for severe COVID-19 illness, with aRRs of 1.95 (95% CI, 1.69-2.26) and 2.86 (95% CI, 2.47-3.32), respectively. CONCLUSIONS AND RELEVANCE: This cross-sectional study found a higher risk of severe COVID-19 illness among children with medical complexity and certain underlying conditions, such as type 1 diabetes, cardiac and circulatory congenital anomalies, and obesity. Health care practitioners could consider the potential need for close observation and cautious clinical management of children with these conditions and COVID-19. |
Technical viability of the YF MAC-HD ELISA kit for use in yellow fever-endemic regions
Goodman CH , Demanou M , Mulders M , Mendez-Rico J , Basile AJ . PLoS Negl Trop Dis 2021 15 (6) e0009417 Yellow fever (YF), an arboviral disease, affects an estimated 200,000 people and causes 30,000 deaths per year and recently has caused major epidemics in Africa and South America. Timely and accurate diagnosis of YF is critical for managing outbreaks and implementing vaccination campaigns. A YF immunoglobulin M (IgM) antibody-capture (MAC) enzyme-linked immunosorbent assay (ELISA) kit, the YF MAC-HD, was successfully introduced starting in 2018 to laboratories in Africa and South America. The YF MAC-HD kit can be performed in 3.5 hours, test up to 24 samples, and includes all reagents necessary to perform the test, except for water used to dilute wash buffer. In 2018 and 2019, a total of 56 laboratory personnel from 39 countries in Africa and South America were trained to use the kit during workshops, followed by take-home YF IgM proficiency testing (PT) exercises. Participants received either a 10- or 20-sample YF PT panel and performed testing using the YF MAC-HD kit. All countries obtained 90% or higher correct results. These results verified the technical viability and transferability of YF MAC-HD kit use for laboratories in YF-endemic countries. |
COVID-19 response by the Hopi Tribe: impact of systems improvement during the first wave on the second wave of the pandemic.
Humeyestewa D , Burke RM , Kaur H , Vicenti D , Jenkins R , Yatabe G , Hirschman J , Hamilton J , Fazekas K , Leslie G , Sehongva G , Honanie K , Tu'tsi E , Mayer O , Rose MA , Diallo Y , Damon S , Zilversmit Pao L , McCraw HM , Talawyma B , Herne M , Nuvangyaoma TL , Welch S , Balajee SA . BMJ Glob Health 2021 6 (5) The Hopi Tribe is a sovereign nation home to ~7500 Hopi persons living primarily in 12 remote villages. The Hopi Tribe, like many other American Indian nations, has been disproportionately affected by COVID-19. On 18 May 2020, a team from the US Centers for Disease Control and Prevention (CDC) was deployed on the request of the tribe in response to increases in COVID-19 cases. Collaborating with Hopi Health Care Center (the reservation's federally run Indian Health Service health facility) and CDC, the Hopi strengthened public health systems and response capacity from May to August including: (1) implementing routine COVID-19 surveillance reporting; (2) establishing the Hopi Incident Management Authority for rapid coordination and implementation of response activities across partners; (3) implementing a community surveillance programme to facilitate early case detection and educate communities on COVID-19 prevention; and (4) applying innovative communication strategies to encourage mask wearing, hand hygiene and physical distancing. These efforts, as well as community adherence to mitigation measures, helped to drive down cases in August. As cases increased in September-November, the improved capacity gained during the first wave of the pandemic enabled the Hopi leadership to have real-time awareness of the changing epidemiological landscape. This prompted rapid response coordination, swift scale up of health communications and redeployment of the community surveillance programme. The Hopi experience in strengthening their public health systems to better confront COVID-19 may be informative to other indigenous peoples as they also respond to COVID-19 within the context of disproportionate burden. |
Late conditions diagnosed 1-4 months following an initial COVID-19 encounter: a matched cohort study using inpatient and outpatient administrative data - United States, March 1-June 30, 2020.
Chevinsky JR , Tao G , Lavery AM , Kukielka EA , Click ES , Malec D , Kompaniyets L , Bruce BB , Yusuf H , Goodman AB , Dixon MG , Nakao JH , Datta SD , Mac Kenzie WR , Kadri S , Saydah S , Giovanni JE , Gundlapalli AV . Clin Infect Dis 2021 73 S5-S16 BACKGROUND: Late sequelae of COVID-19 have been reported; however, few studies have investigated the time-course or incidence of late new COVID-19-related health conditions (post-COVID conditions) after COVID-19 diagnosis. Studies distinguishing post-COVID conditions from late conditions caused by other etiologies are lacking. Using data from a large administrative all-payer database, we assessed the type, association, and timing of post-COVID conditions following COVID-19 diagnosis. METHODS: Using the Premier Healthcare Database Special COVID-19 Release (PHD-SR) (release date, October 20, 2020) data, during March-June 2020, 27,589 inpatients and 46,857 outpatients diagnosed with COVID-19 (case-patients) were 1:1 matched with patients without COVID-19 through the 4-month follow-up period (control-patients) by using propensity score matching. In this matched-cohort study, adjusted odds ratios were calculated to assess for late conditions that were more common in case-patients compared with control-patients. Incidence proportion was calculated for conditions that were more common in case-patients than control-patients during 31-120 days following a COVID-19 encounter. RESULTS: During 31-120 days after an initial COVID-19 inpatient hospitalization, 7.0% of adults experienced at least one of five post-COVID conditions. Among adult outpatients with COVID-19, 7.7% experienced at least one of ten post-COVID conditions. During 31-60 days after an initial outpatient encounter, adults with COVID-19 were 2.8 times as likely to experience acute pulmonary embolism as outpatient control-patients and were also more likely to experience a range of conditions affecting multiple body systems (e.g. nonspecific chest pain, fatigue, headache, and respiratory, nervous, circulatory, and gastrointestinal system symptoms) than outpatient control-patients. Children with COVID-19 were not more likely to experience late conditions than children without COVID-19. CONCLUSIONS: These findings add to the evidence of late health conditions possibly related to COVID-19 in adults following COVID-19 diagnosis and can inform health care practice and resource planning for follow-up COVID-19 care. |
Risk of Clinical Severity by Age and Race/Ethnicity Among Adults Hospitalized for COVID-19-United States, March-September 2020.
Pennington AF , Kompaniyets L , Summers AD , Danielson ML , Goodman AB , Chevinsky JR , Preston LE , Schieber LZ , Namulanda G , Courtney J , Strosnider HM , Boehmer TK , Mac Kenzie WR , Baggs J , Gundlapalli AV . Open Forum Infect Dis 2021 8 (2) ofaa638 BACKGROUND: Older adults and people from certain racial and ethnic groups are disproportionately represented in coronavirus disease 2019 (COVID-19) hospitalizations and deaths. METHODS: Using data from the Premier Healthcare Database on 181( )813 hospitalized adults diagnosed with COVID-19 during March-September 2020, we applied multivariable log-binomial regression to assess the associations between age and race/ethnicity and COVID-19 clinical severity (intensive care unit [ICU] admission, invasive mechanical ventilation [IMV], and death) and to determine whether the impact of age on clinical severity differs by race/ethnicity. RESULTS: Overall, 84( )497 (47%) patients were admitted to the ICU, 29( )078 (16%) received IMV, and 27( )864 (15%) died in the hospital. Increased age was strongly associated with clinical severity when controlling for underlying medical conditions and other covariates; the strength of this association differed by race/ethnicity. Compared with non-Hispanic White patients, risk of death was lower among non-Hispanic Black patients (adjusted risk ratio, 0.96; 95% CI, 0.92-0.99) and higher among Hispanic/Latino patients (risk ratio [RR], 1.15; 95% CI, 1.09-1.20), non-Hispanic Asian patients (RR, 1.16; 95% CI, 1.09-1.23), and patients of other racial and ethnic groups (RR, 1.13; 95% CI, 1.06-1.21). Risk of ICU admission and risk of IMV were elevated among some racial and ethnic groups. CONCLUSIONS: These results indicate that age is a driver of poor outcomes among hospitalized persons with COVID-19. Additionally, clinical severity may be elevated among patients of some racial and ethnic minority groups. Public health strategies to reduce severe acute respiratory syndrome coronavirus 2 infection rates among older adults and racial and ethnic minorities are essential to reduce poor outcomes. |
Optimising pyrazinamide for the treatment of tuberculosis
Zhang N , Savic RM , Boeree MJ , Peloquin C , Weiner M , Heinrich N , Bliven-Sizemore E , Phillips PP , Hoelscher M , Whitworth W , Morlock G , Posey J , Stout JE , Mac Kenzie W , Aarnoutse R , Dooley KE . Eur Respir J 2021 58 (1) Pyrazinamide is a potent sterilising agent that shortens the treatment duration needed to cure tuberculosis. It is synergistic with novel and existing drugs for tuberculosis. The dose of pyrazinamide that optimises efficacy while remaining safe is uncertain, as is its potential role in shortening treatment duration further.Pharmacokinetic data, sputum culture, and safety laboratory results were compiled from TBTC Studies 27 and 28 and PanACEA MAMS-TB, multi-center Phase 2 trials in which participants received rifampicin (range 10-35 mg·kg(-1)), pyrazinamide (range 20-30 mg·kg(-1)), plus two companion drugs. Pyrazinamide pharmacokinetic-pharmacodynamic (PK/PD) and PK-toxicity analyses were performed.In TBTC studies (n=77), higher pyrazinamide maximum concentration (Cmax) was associated with shorter time to culture conversion (TTCC) and higher probability of two-month culture conversion (p-value<0.001). Parametric survival analyses showed that relationships varied geographically, with steeper PK-PD relationships seen among non-African than African participants. In PanACEA MAMS-TB (n=363), TTCC decreased as pyrazinamide Cmax increased and varied by rifampicin Cmax (p-value<0.01). Modeling and simulation suggested that very high doses of pyrazinamide (>4500 mg) or increasing both pyrazinamide and rifampicin would be required to reach targets associated with treatment shortening. Combining all trials, liver toxicity was rare (3.9% with Grade 3 or higher liver function tests, LFT), and no relationship was seen between pyrazinamide Cmax and LFT levels.Pyrazinamide's microbiologic efficacy increases with increasing drug concentrations. Optimising pyrazinamide alone, though, is unlikely to be sufficient to allow tuberculosis treatment shortening; rather, rifampicin dose would need to be increased in parallel. |
Persistence of IgM antibodies after vaccination with live attenuated Japanese encephalitis vaccine
Hills S , Van Keulen A , Feser J , Panella A , Letson B , Staples E , Marfin T , Brault A . Am J Trop Med Hyg 2020 104 (2) 576-579 Japanese encephalitis (JE) is a vaccine-preventable, mosquito-borne disease. Substantial progress with JE control in Asia has been made during the past decade, with most endemic countries now having JE vaccination programs, commonly using live attenuated SA14-14-2 JE vaccine (CD-JEV). If a child develops encephalitis during the weeks to months following CD-JEV vaccination and anti-JE virus IgM (JE IgM) antibody is detected in serum, the question arises if this is JE virus infection indicating vaccine failure, or persistent JE IgM antibody postvaccination. To better understand JE IgM seropositivity following vaccination, sera from 268 children from a previous CD-JEV study were tested by two different JE IgM assays to determine JE IgM antibody frequency on days 28, 180, and 365 postvaccination. With the CDC JE IgM antibody capture ELISA (MAC-ELISA), 110 children (41%) had JE IgM positive or equivocal results on their day 28 sample, and eight (3%) and two (1%) had positive or equivocal results on day 180 and day 365 samples, respectively. With the Inbios JE Detect™ MAC-ELISA, 118 (44%) children had positive or equivocal results on day 28 sample, and three (1%) and one (0.4%) had positive or equivocal results on day 180 and day 365 samples, respectively. Our results indicate that more than 40% children vaccinated with CD-JEV can have JE IgM antibodies in their serum at 1 month postvaccination but JE IgM antibody is rare by 6 months. These data will help healthcare workers assess the likelihood that JE IgM antibodies in the serum of a child with encephalitis after vaccination are vaccine related. |
Characteristics of Hospitalized COVID-19 Patients Discharged and Experiencing Same-Hospital Readmission - United States, March-August 2020.
Lavery AM , Preston LE , Ko JY , Chevinsky JR , DeSisto CL , Pennington AF , Kompaniyets L , Datta SD , Click ES , Golden T , Goodman AB , Mac Kenzie WR , Boehmer TK , Gundlapalli AV . MMWR Morb Mortal Wkly Rep 2020 69 (45) 1695-1699 Coronavirus disease 2019 (COVID-19) is a complex clinical illness with potential complications that might require ongoing clinical care (1-3). Few studies have investigated discharge patterns and hospital readmissions among large groups of patients after an initial COVID-19 hospitalization (4-7). Using electronic health record and administrative data from the Premier Healthcare Database,* CDC assessed patterns of hospital discharge, readmission, and demographic and clinical characteristics associated with hospital readmission after a patient's initial COVID-19 hospitalization (index hospitalization). Among 126,137 unique patients with an index COVID-19 admission during March-July 2020, 15% died during the index hospitalization. Among the 106,543 (85%) surviving patients, 9% (9,504) were readmitted to the same hospital within 2 months of discharge through August 2020. More than a single readmission occurred among 1.6% of patients discharged after the index hospitalization. Readmissions occurred more often among patients discharged to a skilled nursing facility (SNF) (15%) or those needing home health care (12%) than among patients discharged to home or self-care (7%). The odds of hospital readmission increased with age among persons aged ≥65 years, presence of certain chronic conditions, hospitalization within the 3 months preceding the index hospitalization, and if discharge from the index hospitalization was to a SNF or to home with health care assistance. These results support recent analyses that found chronic conditions to be significantly associated with hospital readmission (6,7) and could be explained by the complications of underlying conditions in the presence of COVID-19 (8), COVID-19 sequelae (3), or indirect effects of the COVID-19 pandemic (9). Understanding the frequency of, and risk factors for, readmission can inform clinical practice, discharge disposition decisions, and public health priorities such as health care planning to ensure availability of resources needed for acute and follow-up care of COVID-19 patients. With the recent increases in cases nationwide, hospital planning can account for these increasing numbers along with the potential for at least 9% of patients to be readmitted, requiring additional beds and resources. |
Comparison of Zika virus inactivation methods for reagent production and disinfection methods
Chida AS , Goldstein JM , Lee J , Tang X , Bedi K , Herzegh O , Moon JL , Petway D , Bagarozzi DAJr , Hughes LJ . J Virol Methods 2020 287 114004 Zika virus (ZIKV) infection remains a public health concern necessitating demand for long-term virus production for diagnostic assays and R&D activities. Inactivated virus constitutes an important component of the Trioplex rRT-PCR assay and serological IgM assay (MAC-ELISA). The aim of our study is to establish standard methods of ZIKV inactivation while maintaining antigenicity and RNA integrity. We tested viral supernatants by four different inactivation methods: 1. Heat inactivation at 56 °C and 60 °C; 2. Gamma-Irradiation; 3. Chemical inactivation by Beta-propiolactone (BPL) and 4. Fast-acting commercial disinfecting agents. Effectivity was measured by cytopathic effect (CPE) and plaque assay. RNA stability and antigenicity were measured by RT-PCR and MAC-ELISA, respectively. Results: Heat inactivation: Low titer samples, incubated at 56 °C for 2 hrs, showed neither CPE or plaques compared to high titer supernatants that required 2.5 hrs. Inactivation occurred at 60 °C for 60 min with all virus titers. Gamma irradiation: Samples irradiated at ≥3 Mrad for low virus concentrations and ≥5Mrad for high virus titer completely inactivated virus. Chemical Inactivation: Neither CPE nor plaques were observed with ≥0.045% BPL inactivation of ZIKV. Disinfectant: Treatment of viral supernatants with Micro-Chem Plus(TM), inactivated virus in 2 min, whereas, Ethanol (70%) and STERIS Coverage® Spray TB inactivated the virus in 5 min. |
Hydroxychloroquine and Chloroquine Prescribing Patterns by Provider Specialty Following Initial Reports of Potential Benefit for COVID-19 Treatment - United States, January-June 2020.
Bull-Otterson L , Gray EB , Budnitz DS , Strosnider HM , Schieber LZ , Courtney J , García MC , Brooks JT , Mac Kenzie WR , Gundlapalli AV . MMWR Morb Mortal Wkly Rep 2020 69 (35) 1210-1215 Hydroxychloroquine and chloroquine, primarily used to treat autoimmune diseases and to prevent and treat malaria, received national attention in early March 2020, as potential treatment and prophylaxis for coronavirus disease 2019 (COVID-19) (1). On March 20, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for chloroquine phosphate and hydroxychloroquine sulfate in the Strategic National Stockpile to be used by licensed health care providers to treat patients hospitalized with COVID-19 when the providers determine the potential benefit outweighs the potential risk to the patient.* Following reports of cardiac and other adverse events in patients receiving hydroxychloroquine for COVID-19 (2), on April 24, 2020, FDA issued a caution against its use(†) and on June 15, rescinded its EUA for hydroxychloroquine from the Strategic National Stockpile.(§) Following the FDA's issuance of caution and EUA rescindment, on May 12 and June 16, the federal COVID-19 Treatment Guidelines Panel issued recommendations against the use of hydroxychloroquine or chloroquine to treat COVID-19; the panel also noted that at that time no medication could be recommended for COVID-19 pre- or postexposure prophylaxis outside the setting of a clinical trial (3). However, public discussion concerning the effectiveness of these drugs on outcomes of COVID-19 (4,5), and clinical trials of hydroxychloroquine for prophylaxis of COVID-19 continue.(¶) In response to recent reports of notable increases in prescriptions for hydroxychloroquine or chloroquine (6), CDC analyzed outpatient retail pharmacy transaction data to identify potential differences in prescriptions dispensed by provider type during January-June 2020 compared with the same period in 2019. Before 2020, primary care providers and specialists who routinely prescribed hydroxychloroquine, such as rheumatologists and dermatologists, accounted for approximately 97% of new prescriptions. New prescriptions by specialists who did not typically prescribe these medications (defined as specialties accounting for ≤2% of new prescriptions before 2020) increased from 1,143 prescriptions in February 2020 to 75,569 in March 2020, an 80-fold increase from March 2019. Although dispensing trends are returning to prepandemic levels, continued adherence to current clinical guidelines for the indicated use of these medications will ensure their availability and benefit to patients for whom their use is indicated (3,4), because current data on treatment and pre- or postexposure prophylaxis for COVID-19 indicate that the potential benefits of these drugs do not appear to outweigh their risks. |
Single oral dose for HIV pre or post-exposure prophylaxis: user desirability and biological efficacy in macaques
Massud I , Ruone S , Zlotorzynska M , Haaland R , Mills P , Cong ME , Kelley K , Johnson R , Holder A , Dinh C , Khalil G , Pan Y , Kelley CF , Sanchez T , Heneine W , Garcia-Lerma JG . EBioMedicine 2020 58 102894 BACKGROUND: Daily oral pre- or post-exposure prophylaxis (PrEP or PEP) is highly effective in preventing HIV infection. However, many people find it challenging to adhere to a daily oral regimen. Chemoprophylaxis with single oral doses of antiretroviral drugs taken before or after sex may better adapt to changing or unanticipated sexual practices and be a desirable alternative to daily PrEP or PEP. We investigated willingness to use a single oral pill before or after sex among men who have sex with men (MSM) and assessed the biological efficacy of a potent antiretroviral combination containing elvitegravir (EVG), emtricitabine (FTC), and tenofovir alafenamide (TAF). METHODS: Data on willingness to use single-dose PrEP or PEP were obtained from the 2017 cycle of the American Men's Internet Survey (AMIS), an annual online behavioral surveillance survey of MSM in the United States. Antiretroviral drug levels were measured in humans and macaques to define drug distribution in rectal tissue and identify clinically relevant doses for macaque modeling studies. The biological efficacy of a single dose of FTC/TAF/EVG as PrEP or PEP was investigated using a repeat-challenge macaque model of rectal HIV infection. FINDINGS: Through pharmacokinetic assessment in humans and macaques we found that EVG penetrates and concentrates in rectal tissues supporting its addition to FTC/TAF to boost and extend chemoprophylactic activity. Efficacy estimates for a single oral dose given to macaques 4h before or 2h after SHIV exposure was 91•7%[35•7%-98•9%] and 100%, respectively, compared to 80•1%[13•9%-95•4%] and 64•6%[-19•4%-89•5%] when single doses were given 6 and 24h post challenge, respectively. A two-dose regimen at 24h and 48h after exposure was also protective [77•1%[1•7%-94•7%]. INTERPRETATION: Informed by user willingness, human and macaque pharmacokinetic data, and preclinical efficacy we show that single-dose prophylaxis before or after sex is a promising HIV prevention strategy. Carefully designed clinical trials are needed to determine if any of these strategies will be effective in humans. FUNDING: Funded by CDC intramural funds, CDC contract HCVJCG2-2016-03948 (to CFK), and a grant from the MAC AIDS Fund and by the National Institutes of Health [P30AI050409] - the Emory Center for AIDS Research (to MZ and TS). |
Reporting and assessing the quality of diagnostic accuracy studies for cervical cancer screening and management
Clarke MA , Darragh TM , Nelson E , Unger ER , Zuna R , Cremer M , Stockdale CK , Einstein MH , Wentzensen N . J Low Genit Tract Dis 2020 24 (2) 157-166 OBJECTIVE: We adapted the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool for studies of cervical cancer screening and management and used the adapted tool to evaluate the quality of studies included in a systematic review supporting the 2019 Risk-Based Management Consensus Guidelines. METHODS: We evaluated the quality of all studies included in our systematic review for postcolposcopy (n = 5) and posttreatment (n = 23) surveillance using QUADAS-2 criteria. Subsequently, we adapted signaling questions to indications of cervical cancer screening and management. An iterative process was carried out to evaluate interrater agreement between 2 study authors (M.A.C. and N.W.). Discrepant ratings were discussed, and criteria were adapted accordingly. We also evaluated the influence of study quality on risk estimates and between study variation using stratified subgroup meta-analyses. RESULTS: Twelve signaling questions for bias assessment that were adapted to or newly developed for cervical cancer screening and management are described here. Interrater agreement on bias assessment increased from 70% to 83% during the adaptation process. Detailed assessment of bias and applicability showed that all studies on postcolposcopy management and 90% of studies on posttreatment management had high risk of bias in at least 1 domain. Most commonly, high risk of bias was observed for the patient selection domain, indicating the heterogeneity of study designs and clinical practice in reported studies. CONCLUSIONS: The adapted QUADAS-2 will have broad application for researchers, evidence evaluators, and journals who are interested in designing, conducting, evaluating, and publishing studies for cervical cancer screening and management. |
Comprehensive evaluation of differential serodiagnosis between Zika and dengue viral infections
Chao DY , Whitney MT , Davis BS , Medina FA , Munoz JL , Chang GJ . J Clin Microbiol 2019 57 (3) Diagnostic testing for Zika virus (ZIKV) or dengue virus (DENV) infection can be accomplished by a nucleic acid detection method; however, a negative result does not exclude infection due to the low virus titer during infection depending on the timing of sample collection. Therefore, a ZIKV- or DENV-specific serological assay is essential for the accurate diagnosis of patients and to mitigate potential severe health outcomes. A retrospective study design with dual approaches of collecting human serum samples for testing was developed. All serum samples were extensively evaluated by using both noninfectious wild-type (wt) virus-like particles (VLPs) and soluble nonstructural protein 1 (NS1) in the standard immunoglobulin M (IgM) antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA). Both ZIKV-derived wt-VLP- and NS1-MAC-ELISAs were found to have similar sensitivities for detecting anti-premembrane/envelope and NS1 antibodies from ZIKV-infected patient sera, although lower cross-reactivity to DENV2/3-NS1 was observed. Furthermore, group cross-reactive (GR)-antibody-ablated homologous fusion peptide-mutated (FP)-VLPs consistently showed higher positive-to-negative values than homologous wt-VLPs. Therefore, we used DENV-2/3 and ZIKV FP-VLPs to develop a novel, serological algorithm for differentiating ZIKV from DENV infection. Overall, the sensitivity and specificity of the FP-VLP-MAC-ELISA and the NS1-MAC-ELISA were each higher than 80%, with no statistical significance. The accuracy can reach up to 95% with the combination of FP-VLP and NS1 assays. In comparison to current guidelines using neutralization tests to measure ZIKV antibody, this approach can facilitate laboratory screening for ZIKV infection, especially in regions where DENV infection is endemic and capacity for neutralization testing does not exist. |
Bacterial factors that predict relapse after tuberculosis therapy
Colangeli R , Jedrey H , Kim S , Connell R , Ma S , Chippada Venkata UD , Chakravorty S , Gupta A , Sizemore EE , Diem L , Sherman DR , Okwera A , Dietze R , Boom WH , Johnson JL , Mac Kenzie WR , Alland D . N Engl J Med 2018 379 (9) 823-833 BACKGROUND: Approximately 5% of patients with drug-susceptible tuberculosis have a relapse after 6 months of first-line therapy, as do approximately 20% of patients after 4 months of short-course therapy. We postulated that by analyzing pretreatment isolates of Mycobacterium tuberculosis obtained from patients who subsequently had a relapse or were cured, we could determine any correlations between the minimum inhibitory concentration (MIC) of a drug below the standard resistance breakpoint and the relapse risk after treatment. METHODS: Using data from the Tuberculosis Trials Consortium Study 22 (development cohort), we assessed relapse and cure isolates to determine the MIC values of isoniazid and rifampin that were below the standard resistance breakpoint (0.1 mug per milliliter for isoniazid and 1.0 mug per milliliter for rifampin). We combined this analysis with clinical, radiologic, and laboratory data to generate predictive relapse models, which we validated by analyzing data from the DMID 01-009 study (validation cohort). RESULTS: In the development cohort, the mean (+/-SD) MIC of isoniazid below the breakpoint was 0.0334+/-0.0085 mug per milliliter in the relapse group and 0.0286+/-0.0092 mug per milliliter in the cure group, which represented a higher value in the relapse group by a factor of 1.17 (P=0.02). The corresponding MIC values of rifampin were 0.0695+/-0.0276 and 0.0453+/-0.0223 mug per milliliter, respectively, which represented a higher value in the relapse group by a factor of 1.53 (P<0.001). Higher MIC values remained associated with relapse in a multivariable analysis that included other significant between-group differences. In an analysis of receiver-operating-characteristic curves of relapse based on these MIC values, the area under the curve (AUC) was 0.779. In the development cohort, the AUC in a multivariable model that included MIC values was 0.875. In the validation cohort, the MIC values either alone or combined with other patient characteristics were also predictive of relapse, with AUC values of 0.964 and 0.929, respectively. The use of a model score for the MIC values of isoniazid and rifampin to achieve 75.0% sensitivity in cross-validation analysis predicted relapse with a specificity of 76.5% in the development cohort and a sensitivity of 70.0% and a specificity of 100% in the validation cohort. CONCLUSIONS: In pretreatment isolates of M. tuberculosis with decrements of MIC values of isoniazid or rifampin below standard resistance breakpoints, higher MIC values were associated with a greater risk of relapse than lower MIC values. (Funded by the National Institute of Allergy and Infectious Diseases.). |
Elevated Plasma Moxifloxacin Concentrations and SLCO1B1 g.-11187G>A Polymorphism in Adults with Pulmonary Tuberculosis.
Weiner M , Gelfond J , Johnson-Pais TL , Engle M , Peloquin CA , Johnson JL , Sizemore EE , Mac Kenzie WR . Antimicrob Agents Chemother 2018 62 (5) Moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals and bactericidal activity against Mycobacterium tuberculosis However, moxifloxacin plasma concentrations are variable between patients. We evaluated whether human gene polymorphisms affect moxifloxacin plasma concentrations in tuberculosis patients from two geographic regions. We enrolled a convenience sample of 49 adults with drug-sensitive pulmonary tuberculosis from Africa and the United State s enrolled in two treatment trials of moxifloxacin as part of multidrug therapy. Pharmacokinetic parameters were evaluated by noncompartmental techniques. Human single-nucleotide polymorphisms of transporter genes were evaluated with analysis of covariance on moxifloxacin exposure and peak concentration (Cmax). Moxifloxacin area under the concentration-time curve from 0 to 24 h (AUC0-24) and Cmax were significantly increased by drug mg/kg dosage and genotype of variant g.-11187G>A in the SLCO1B1 gene (rs4149015), but not by geographic region. Median moxifloxacin AUC0-24 was 46% higher and Cmax 30% higher in 4 (8% of) participants who had the SLCO1B1 g.-11187 AG genotype compared with 45 participants who had the wild type GG genotype (median from model, AUC0-24 34.4 vs. 23.6 mug*h/mL, P =.005; Cmax 3.5 vs. 2.7 mug/mL, P =.009, ANCOVA). Because moxifloxacin exhibits concentration-dependent prolongation of human QTc intervals, and prolonged QTc intervals are associated with cardiac arrhythmia, further study is needed to evaluate risk associated with the SLCO1B1 g.-11187G>A variant. |
An assessment of information exchange practices, challenges, and opportunities to support US disease surveillance in 3 states
Garcia MC , Garrett NY , Singletary V , Brown S , Hennessy-Burt T , Haney G , Link K , Tripp J , Mac Kenzie WR , Yoon P . J Public Health Manag Pract 2017 24 (6) 546-553 BACKGROUND: State and local public health agencies collect and use surveillance data to identify outbreaks, track cases, investigate causes, and implement measures to protect the public-s health through various surveillance systems and data exchange practices. PURPOSE: The purpose of this assessment was to better understand current practices at state and local public health agencies for collecting, managing, processing, reporting, and exchanging notifiable disease surveillance information. METHODS: Over an 18-month period (January 2014-June 2015), we evaluated the process of data exchange between surveillance systems, reporting burdens, and challenges within 3 states (California, Idaho, and Massachusetts) that were using 3 different reporting systems. RESULTS: All 3 states use a combination of paper-based and electronic information systems for managing and exchanging data on reportable conditions within the state. The flow of data from local jurisdictions to the state health departments varies considerably. When state and local information systems are not interoperable, manual duplicative data entry and other work-arounds are often required. The results of the assessment show the complexity of disease reporting at the state and local levels and the multiple systems, processes, and resources engaged in preparing, processing, and transmitting data that limit interoperability and decrease efficiency. CONCLUSIONS: Through this structured assessment, the Centers for Disease Control and Prevention (CDC) has a better understanding of the complexities for surveillance of using commercial off-the-shelf data systems (California and Massachusetts), and CDC-developed National Electronic Disease Surveillance System Base System. More efficient data exchange and use of data will help facilitate interoperability between National Notifiable Diseases Surveillance Systems. |
Evaluation of syndromic surveillance systems in 6 US state and local health departments
Thomas MJ , Yoon PW , Collins JM , Davidson AJ , Mac Kenzie WR . J Public Health Manag Pract 2017 24 (3) 235-240 OBJECTIVE: Evaluating public health surveillance systems is critical to ensuring that conditions of public health importance are appropriately monitored. Our objectives were to qualitatively evaluate 6 state and local health departments that were early adopters of syndromic surveillance in order to (1) understand the characteristics and current uses, (2) identify the most and least useful syndromes to monitor, (3) gauge the utility for early warning and outbreak detection, and (4) assess how syndromic surveillance impacted their daily decision making. DESIGN: We adapted evaluation guidelines from the Centers for Disease Control and Prevention and gathered input from the Centers for Disease Control and Prevention subject matter experts in public health surveillance to develop a questionnaire. PARTICIPANTS: We interviewed staff members from a convenience sample of 6 local and state health departments with syndromic surveillance programs that had been in operation for more than 10 years. RESULTS: Three of the 6 interviewees provided an example of using syndromic surveillance to identify an outbreak (ie, cluster of foodborne illness in 1 jurisdiction) or detect a surge in cases for seasonal conditions (eg, influenza in 2 jurisdictions) prior to traditional, disease-specific systems. Although all interviewees noted that syndromic surveillance has not been routinely useful or efficient for early outbreak detection or case finding in their jurisdictions, all agreed that the information can be used to improve their understanding of dynamic disease control environments and conditions (eg, situational awareness) in their communities. CONCLUSION: In the jurisdictions studied, syndromic surveillance may be useful for monitoring the spread and intensity of large outbreaks of disease, especially influenza; enhancing public health awareness of mass gatherings and natural disasters; and assessing new, otherwise unmonitored conditions when real-time alternatives are unavailable. Future studies should explore opportunities to strengthen syndromic surveillance by including broader access to and enhanced analysis of text-related data from electronic health records. Health departments may accelerate the development and use of syndromic surveillance systems, including the improvement of the predictive value and strengthening the early outbreak detection capability of these systems. These efforts support getting the right information to the right people at the right time, which is the overarching goal of CDC's Surveillance Strategy. |
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