Last data update: Sep 23, 2024. (Total: 47723 publications since 2009)
Records 1-30 (of 105 Records) |
Query Trace: Becker M [original query] |
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Epidemiology of pediatric astrovirus gastroenteritis in a Nicaraguan Birth Cohort
Rubinstein RJ , Gutiérrez L , Toval-Ruíz C , Hammond K , Bode L , Vinjé J , Vilchez S , Becker-Dreps S , Bucardo F , Vielot NA , Reyes Y . Open Forum Infect Dis 2024 11 (9) ofae465 BACKGROUND: Astrovirus is a leading cause of acute gastroenteritis in children worldwide. However, few prospective studies have analyzed astrovirus in community-dwelling pediatric populations in low- and middle-income countries. METHODS: We assessed the incidence, risk factors, clinical characteristics, genotypes, viral coinfections, and time distribution of astrovirus gastroenteritis in 443 healthy Nicaraguan children born in 2017 to 2018 who were followed for 36 months. Children were recruited from hospitals and birth records in an economically diverse neighborhood of León city. Astrovirus-positive episodes and genotypes were identified from stool with reverse transcription quantitative polymerase chain reaction and Sanger sequencing. RESULTS: Of 1708 total specimens tested, 80 children (18%) experienced at least 1 astrovirus episode, and 9 experienced repeat episodes, mostly during the rainy season (May-October). Initial astrovirus episodes were not associated with a lowered risk against future episodes. In exploratory analyses, home toilets were associated with a lower risk of future astrovirus episodes (hazard ratio, 0.19; 95% CI, .04-.91). Human astrovirus 5 episodes, representing 15% of all typed episodes, were associated with longer diarrhea and more symptomatic rotavirus coinfections. CONCLUSIONS: Astrovirus was a common cause of gastroenteritis in this cohort, and future studies should clarify the role of astrovirus genotype in clinical infection severity. |
Charting the impact of maternal antibodies and repeat exposures on sapovirus immunity in early childhood from a Nicaraguan birth cohort
Bucardo F , Mallory ML , González F , Reyes Y , Vielot NA , Yount BL , Sims AC , Nguyen C , Cross K , Toval-Ruíz C , Gutiérrez L , Vinjé J , Baric RS , Lindesmith LC , Becker-Dreps S . J Infect Dis 2024 BACKGROUND: Sapovirus is an important cause of acute gastroenteritis in childhood. While vaccines against sapovirus may reduce gastroenteritis burden, a major challenge to their development is a lack of information about natural immunity. METHODS: We measured sapovirus-specific IgG in serum collected, between 2017 and 2020, of mothers soon after delivery and at 6 time points in Nicaraguan children until 3 years of age (n=112 dyads) using virus-like particles representing three sapovirus genotypes (GI.1, GI.2, GV.1). RESULTS: Sixteen (14.3%) of the 112 children experienced at least one sapovirus gastroenteritis episode, of which GI.1 was the most common genotype. Seroconversion to GI.1 and GI.2 was most common between 5 and 12 months of age, while seroconversion to GV.1 peaked at 18 to 24 months of age. All children who experienced sapovirus GI.1 gastroenteritis seroconverted and developed genotype-specific IgG. The impact of sapovirus exposure on population immunity was determined using antigenic cartography: newborns share their mothers' broadly binding IgG responses, which declined at 5 months of age and then increased as infants experienced natural sapovirus infections. CONCLUSION: By tracking humoral immunity to sapovirus over the first 3 years of life, this study provides important insights for the design and timing of future pediatric sapovirus vaccines. |
Programme Science: a route to transformative change to improve population-level impact for global HIV and sexually transmitted infections
Becker ML , Shahmanesh M , Aral SO . J Int AIDS Soc 2024 27 Suppl 2 e26300 |
Correction and Republication: Symptoms of Depression, Anxiety, Post-Traumatic Stress Disorder, and Suicidal Ideation Among State, Tribal, Local, and Territorial Public Health Workers During the COVID-19 Pandemic - United States, March-April 2021
Bryant-Genevier J , Rao CY , Lopes-Cardozo B , Kone A , Rose C , Thomas I , Orquiola D , Lynfield R , Shah D , Freeman L , Becker S , Williams A , Gould DW , Tiesman H , Lloyd G , Hill L , Byrkit R . MMWR Morb Mortal Wkly Rep 12/28/2021 70 (48) 1679 On July 2, 2021, MMWR published “Symptoms of Depression, Anxiety, Post-Traumatic Stress Disorder, and Suicidal Ideation Among State, Tribal, Local, and Territorial Public Health Workers During the COVID-19 Pandemic — United States, March–April 2021” (1). On October 12, 2021, the authors informed MMWR that some data were inaccurate because 420 incomplete participant responses were incorrectly assigned scores for depression. This error resulted in a change in overall depression prevalence from 32.0% to 30.8%, and other similar changes in stratified prevalences of depression, prevalence ratios of depression, and the overall proportion of respondents who reported at least one mental health condition. The authors have corrected the MMWR report by excluding the 420 records from the depression analysis and confirmed that the interpretation and the conclusions of the original report were not affected by these corrections. MMWR has republished the report (2), which includes the original report with clearly marked corrections in supplementary materials. |
HIV preexposure prophylaxis with emtricitabine and tenofovir disoproxil fumarate among cisgender women
Marrazzo J , Tao L , Becker M , Leech AA , Taylor AW , Ussery F , Kiragu M , Reza-Paul S , Myers J , Bekker LG , Yang J , Carter C , de Boer M , Das M , Baeten JM , Celum C . Jama 2024 IMPORTANCE: Emtricitabine and tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP) is highly effective in cisgender men who have sex with men (MSM) when adherence is high (>4 doses/week). Real-world effectiveness and adherence with F/TDF for PrEP in cisgender women is less well characterized. OBJECTIVE: To characterize the effectiveness of F/TDF for PrEP and its relationship with adherence in cisgender women. DESIGN, SETTING, AND PARTICIPANTS: Data were pooled from 11 F/TDF PrEP postapproval studies conducted in 6 countries that included 6296 cisgender women aged 15 to 69 years conducted from 2012 to 2020. HIV incidence was evaluated according to adherence level measured objectively (tenofovir diphosphate concentration in dried blood spots or tenofovir concentration in plasma; n = 288) and subjectively (electronic pill cap monitoring, pill counts, self-report, and study-reported adherence scale; n = 2954) using group-based trajectory modeling. EXPOSURES: F/TDF prescribed orally once a day. HIV incidence was analyzed in subgroups based on adherence trajectory. MAIN OUTCOMES AND MEASURES: HIV incidence. RESULTS: Of the 6296 participants, 46% were from Kenya, 28% were from South Africa, 21% were from India, 2.9% were from Uganda, 1.6% were from Botswana, and 0.8% were from the US. The mean (SD) age at PrEP initiation across all studies was 25 (7) years, with 61% of participants being younger than 25 years. The overall HIV incidence was 0.72 per 100 person-years (95% CI, 0.51-1.01; 32 incident HIV diagnoses among 6296 participants). Four distinct groups of adherence trajectories were identified: consistently daily (7 doses/week), consistently high (4-6 doses/week), high but declining (from a mean of 4-6 doses/week and then declining), and consistently low (less than 2 doses/week). None of the 498 women with consistently daily adherence acquired HIV. Only 1 of the 658 women with consistently high adherence acquired HIV (incidence rate, 0.13/100 person-years [95% CI, 0.02-0.92]). The incidence rate was 0.49 per 100 person-years (95% CI, 0.22-1.08) in the high but declining adherence group (n = 1166) and 1.27 per 100 person-years (95% CI, 0.53-3.04) in the consistently low adherence group (n = 632). CONCLUSIONS AND RELEVANCE: In a pooled analysis of 11 postapproval studies of F/TDF for PrEP among cisgender women, overall HIV incidence was 0.72 per 100 person-years; individuals with consistently daily or consistently high adherence (4-6 doses/week) to PrEP experienced very low HIV incidence. |
Programme science: a route to effective coverage and population-level impact for HIV and sexually transmitted infection prevention
McClarty LM , Becker ML , García PJ , Garnett GP , Dallabetta GA , Ward H , Aral SO , Blanchard JF . Lancet HIV 2023 10 (12) e825-e834 Improvements in context-specific programming are essential to address HIV and other sexually transmitted and blood-borne infection epidemics globally. A programme science approach emphasises the need for context-specific evidence and knowledge, generated on an ongoing basis, to inform timely and appropriate programmatic decisions. We aim to accelerate and improve the use of embedded research, inquiry, and learning to optimise population-level impact of public health programmes and to introduce an effective programme coverage framework as one tool to facilitate this goal. The framework was developed in partnership with public health experts in HIV and sexually transmitted and blood-borne infections through several workshops and meetings. The framework is a practice-based tool that centres on the use of data from iterative cycles of programme-embedded research and learning, as well as routine programme monitoring, to refine the strategy and implementation of a programme. This programme science approach aims to reduce programme coverage gaps, to optimise impact at the population level, and to achieve effective coverage. This framework should facilitate the generation of programme-embedded research and learning agendas to inform resource allocation, optimise population-level impact, and achieve equitable and effective programme coverage. |
Impact of SARS-CoV-2 infection on the association between laboratory tests and severe outcomes among hospitalized children
Xie J , Kuppermann N , Florin TA , Tancredi DJ , Funk AL , Kim K , Salvadori MI , Yock-Corrales A , Shah NP , Breslin KA , Chaudhari PP , Bergmann KR , Ahmad FA , Nebhrajani JR , Mintegi S , Gangoiti I , Plint AC , Avva UR , Gardiner MA , Malley R , Finkelstein Y , Dalziel SR , Bhatt M , Kannikeswaran N , Caperell K , Campos C , Sabhaney VJ , Chong SL , Lunoe MM , Rogers AJ , Becker SM , Borland ML , Sartori LF , Pavlicich V , Rino PB , Morrison AK , Neuman MI , Poonai N , Simon NE , Kam AJ , Kwok MY , Morris CR , Palumbo L , Ambroggio L , Navanandan N , Eckerle M , Klassen TP , Payne DC , Cherry JC , Waseem M , Dixon AC , Ferre IB , Freedman SB . Open Forum Infect Dis 2023 10 (10) ofad485 BACKGROUND: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations. METHODS: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations. RESULTS: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 10(9)/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 10(9)/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts. CONCLUSIONS: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative. |
Gut microbiome perturbation, antibiotic resistance, and Escherichia coli strain dynamics associated with international travel: a metagenomic analysis
Worby CJ , Sridhar S , Turbett SE , Becker MV , Kogut L , Sanchez V , Bronson RA , Rao SR , Oliver E , Walker AT , Walters MS , Kelly P , Leung DT , Knouse MC , Hagmann SHF , Harris JB , Ryan ET , Earl AM , LaRocque RC . Lancet Microbe 2023 4 (10) e790-e799 BACKGROUND: Culture-based studies have shown that acquisition of extended-spectrum β-lactamase-producing Enterobacterales is common during international travel; however, little is known about the role of the gut microbiome before and during travel, nor about acquisition of other antimicrobial-resistant organisms. We aimed to identify (1) whether the gut microbiome provided colonisation resistance against antimicrobial-resistant organism acquisition, (2) the effect of travel and travel behaviours on the gut microbiome, and (3) the scale and global heterogeneity of antimicrobial-resistant organism acquisition. METHODS: In this metagenomic analysis, participants were recruited at three US travel clinics (Boston, MA; New York, NY; and Salt Lake City, UT) before international travel. Participants had to travel internationally between Dec 8, 2017, and April 30, 2019, and have DNA extractions for stool samples both before and after travel for inclusion. Participants were excluded if they had at least one low coverage sample (<1 million read pairs). Stool samples were collected at home before and after travel, sent to a clinical microbiology laboratory to be screened for three target antimicrobial-resistant organisms (extended-spectrum β-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, and mcr-mediated colistin-resistant Enterobacterales), and underwent DNA extraction and shotgun metagenomic sequencing. We profiled metagenomes for taxonomic composition, antibiotic-resistant gene content, and characterised the Escherichia coli population at the strain level. We analysed pre-travel samples to identify the gut microbiome risk factors associated with acquisition of the three targeted antimicrobial resistant organisms. Pre-travel and post-travel samples were compared to identify microbiome and resistome perturbation and E coli strain acquisition associated with travel. FINDINGS: A total of 368 individuals travelled between the required dates, and 296 had DNA extractions available for both before and after travel. 29 travellers were excluded as they had at least one low coverage sample, leaving a final group of 267 participants. We observed a perturbation of the gut microbiota, characterised by a significant depletion of microbial diversity and enrichment of the Enterobacteriaceae family. Metagenomic strain tracking confirmed that 67% of travellers acquired new strains of E coli during travel that were phylogenetically distinct from their pre-travel strains. We observed widespread enrichment of antibiotic-resistant genes in the gut, with a median 15% (95% CI 10-20, p<1 × 10(-10)) increase in burden (reads per kilobase per million reads). This increase included antibiotic-resistant genes previously classified as threats to public health, which were 56% (95% CI 36-91, p=2 × 10(-11)) higher in abundance after travel than before. Fluoroquinolone antibiotic-resistant genes were aquired by 97 (54%) of 181 travellers with no detected pre-travel carriage. Although we found that visiting friends or relatives, travel to south Asia, and eating uncooked vegetables were risk factors for acquisition of the three targeted antimicrobial resistant organisms, we did not observe an association between the pre-travel microbiome structure and travel-related antimicrobial-resistant organism acquisition. INTERPRETATION: This work highlights a scale of E coli and antimicrobial-resistant organism acquisition by US travellers not apparent from previous culture-based studies, and suggests that strategies to control antimicrobial-resistant organisms addressing international traveller behaviour, rather than modulating the gut microbiome, could be worthwhile. FUNDING: US Centers for Disease Control and Prevention and National Institute of Allergy and Infectious Diseases. |
Infant antibody and B-cell responses following confirmed pediatric GII.17 norovirus infections functionally distinguish GII.17 genetic clusters
Strother CA , Brewer-Jensen PD , Becker-Dreps S , Zepeda O , May S , Gonzalez F , Reyes Y , McElvany BD , Averill AM , Mallory ML , Montmayeur AM , Costantini VP , Vinjé J , Baric RS , Bucardo F , Lindesmith LC , Diehl SA . Front Immunol 2023 14 1229724 Genogroup II (GII) noroviruses are a major cause of diarrheal disease burden in children in both high- and low-income countries. GII.17 noroviruses are composed of distinct genetic clusters (I, II, IIIa, and IIIb) and have shown potential for replacing historically more prevalent GII.4 strains, but the serological basis for GII.17 antigenic diversity has not been studied in children. Utilizing samples from a birth cohort, we investigated antibody and B-cell responses to GII.17 cluster variants in confirmed GII.17 infections in young children as well as demonstrated that the distinct genetic clusters co-circulate. Polyclonal serum antibodies bound multiple clusters but showed cluster-specific blockade activity in a surrogate virus neutralization assay. Antibodies secreted by immortalized memory B cells (MBCs) from an infant GII.17 case were highly specific to GII.17 and exhibited blockade activity against this genotype. We isolated an MBC-derived GII.17-specific Immunoglobulin A (IgA) monoclonal antibody called NVA.1 that potently and selectively blocked GII.17 cluster IIIb and recognized an epitope targeted in serum from cluster IIIb-infected children. These data indicate that multiple antigenically distinct GII.17 variants co-circulate in young children, suggesting retention of cluster diversity alongside potential for immune escape given the existence of antibody-defined cluster-specific epitopes elicited during infection. |
Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission (preprint)
Karthikeyan S , Levy JI , De Hoff P , Humphrey G , Birmingham A , Jepsen K , Farmer S , Tubb HM , Valles T , Tribelhorn CE , Tsai R , Aigner S , Sathe S , Moshiri N , Henson B , Mark AM , Hakim A , Baer NA , Barber T , Belda-Ferre P , Chacón M , Cheung W , Cresini ES , Eisner ER , Lastrella AL , Lawrence ES , Marotz CA , Ngo TT , Ostrander T , Plascencia A , Salido RA , Seaver P , Smoot EW , McDonald D , Neuhard RM , Scioscia AL , Satterlund AM , Simmons EH , Abelman DB , Brenner D , Bruner JC , Buckley A , Ellison M , Gattas J , Gonias SL , Hale M , Hawkins F , Ikeda L , Jhaveri H , Johnson T , Kellen V , Kremer B , Matthews G , McLawhon RW , Ouillet P , Park D , Pradenas A , Reed S , Riggs L , Sanders A , Sollenberger B , Song A , White B , Winbush T , Aceves CM , Anderson C , Gangavarapu K , Hufbauer E , Kurzban E , Lee J , Matteson NL , Parker E , Perkins SA , Ramesh KS , Robles-Sikisaka R , Schwab MA , Spencer E , Wohl S , Nicholson L , McHardy IH , Dimmock DP , Hobbs CA , Bakhtar O , Harding A , Mendoza A , Bolze A , Becker D , Cirulli ET , Isaksson M , Barrett KMS , Washington NL , Malone JD , Schafer AM , Gurfield N , Stous S , Fielding-Miller R , Garfein RS , Gaines T , Anderson C , Martin NK , Schooley R , Austin B , MacCannell DR , Kingsmore SF , Lee W , Shah S , McDonald E , Yu AT , Zeller M , Fisch KM , Longhurst C , Maysent P , Pride D , Khosla PK , Laurent LC , Yeo GW , Andersen KG , Knight R . medRxiv 2022 As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. |
Non-secretor phenotype is associated with less risk of rotavirus-associated acute gastroenteritis in a vaccinated Nicaraguan birth cohort
Reyes Y , St Jean DT , Bowman NM , González F , Mijatovic-Rustempasic S , Becker-Dreps S , Svensson L , Nordgren J , Bucardo F , Vielot NA . J Infect Dis 2023 228 (12) 1739-1747 BACKGROUND: Histo-blood group antigens (HBGAs) have been associated with rotavirus vaccine take; but the effect of these HBGAs on rotavirus incidence and risk remains poorly explored in vaccinated populations. METHODS: Rotavirus-associated acute gastroenteritis (AGE) was assessed in 444 Nicaraguan children followed from birth until 3 years of age. AGE episodes were tested for rotavirus by RT-qPCR and saliva or blood were used to determine the HBGAs phenotypes. Cox proportional hazards models were used to estimate the relative hazard of rotavirus AGE by HBGA phenotypes. RESULTS: Rotavirus was detected in 109 (7%) stool samples from 1,689 AGE episodes over 36 months of observation between June 2017 and July 2021. Forty-six samples were successfully genotyped. Of these, 15 (35%) were rotavirus vaccine strain G1P[8], followed by G8P[8] or G8P[nt] (11, 24%) and equine-like G3P[8] (11, 24%). The overall incidence of rotavirus-associated AGE was 9.2/100 child-years, and was significantly higher in secretor compared to non-secretor children (9.8 vs. 3.5/100 child-years, P = 0.002). CONCLUSION: The non-secretor phenotype was associated with decreased risk of clinical rotavirus vaccine failure in a vaccinated Nicaraguan birth cohort. These results show the importance of secretor status on rotavirus risk, even in vaccinated children. |
Health Care Transition Experiences of Males with Childhood-onset Duchenne and Becker Muscular Dystrophy: Findings from the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) Health Care Transitions and Other Life Experiences Survey
Paramsothy P , Herron AR , Lamb M , Kinnett K , Wolff J , Yang Ml , Oleszek J , Pandya S , Kennedy A , Cooney D , Fox D , Sheehan D . PLoS Curr 2018 10 Introduction: As the proportion of males with Duchenne muscular dystrophy (DMD) surviving into adulthood increases, more information is needed regarding their health care transition planning, an essential process for adolescents and young adults with DMD. The objective of this study was to describe the health care transition experiences of a population of males living with Duchenne or Becker muscular dystrophy (DBMD). Methods: The eligible participants, identified through the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) surveillance project, were 16-31 years old and lived in Arizona, Colorado, Georgia, Iowa, or western New York (n=258). The MD STARnet Health Care Transitions and Other Life Experiences Survey was conducted in 2013 and administered online or in a telephone interview. Sixty-five males (25%) completed the survey. Among non-ambulatory males, response differences were compared by age group. Statistical comparisons were conducted using Fisher's exact test, or when appropriate, the Chisquare test. Results: Twenty-one percent of non-ambulatory males aged 16-18 years, 28% of non-ambulatory males aged 19-23 years, 25% of non-ambulatory males aged 24-30 years, and 18 ambulatory males had a written transition plan. Nineteen percent of non-ambulatory males aged 24-30 years had delayed or gone without needed health care in the past 12 months. Among non-ambulatory males aged 24-30 years, 75% had cardiology providers and 69% had pulmonology providers involved in their care in the past 12 months. Twentyeight percent of non-ambulatory males aged 19-23 years and 25% of non-ambulatory males aged 24-30 years reported that they did not receive health care or other services at least once because they were unable to leave their home. Non-ambulatory males aged 16-18 years (29%) were less likely to have ever discussed how to obtain or keep health insurance as they get older compared to non-ambulatory males aged 24-30 years (69%) (p <0.01). Discussion: This study identified potential barriers to the successful health care transition of males with DBMD. The results of this study may indicate a lack of targeted informational resources and education focused on supporting the transition of young men with DBMD as they age from adolescence into adulthood within the healthcare system. Future studies could determine the reasons for the potential barriers to health care and identify the optimal transition programs for males with DBMD. There are a few online resources on transition available to adolescents and young adults with special health care needs. |
New Lineage of Lassa Virus, Togo, 2016.
Whitmer SLM , Strecker T , Cadar D , Dienes HP , Faber K , Patel K , Brown SM , Davis WG , Klena JD , Rollin PE , Schmidt-Chanasit J , Fichet-Calvet E , Noack B , Emmerich P , Rieger T , Wolff S , Fehling SK , Eickmann M , Mengel JP , Schultze T , Hain T , Ampofo W , Bonney K , Aryeequaye JND , Ribner B , Varkey JB , Mehta AK , Lyon GM 3rd , Kann G , De Leuw P , Schuettfort G , Stephan C , Wieland U , Fries JWU , Kochanek M , Kraft CS , Wolf T , Nichol ST , Becker S , Ströher U , Günther S . Emerg Infect Dis 2018 24 (3) 599-602 We describe a strain of Lassa virus representing a putative new lineage that was isolated from a cluster of human infections with an epidemiologic link to Togo. This finding extends the known range of Lassa virus to Togo. |
Symptoms of Depression, Anxiety, Post-Traumatic Stress Disorder, and Suicidal Ideation Among State, Tribal, Local, and Territorial Public Health Workers During the COVID-19 Pandemic - United States, March-April 2021.
Bryant-Genevier J , Rao CY , Lopes-Cardozo B , Kone A , Rose C , Thomas I , Orquiola D , Lynfield R , Shah D , Freeman L , Becker S , Williams A , Gould DW , Tiesman H , Lloyd G , Hill L , Byrkit R . MMWR Morb Mortal Wkly Rep 2021 70 (48) 1680-1685 Increases in mental health conditions have been documented among the general population and health care workers since the start of the COVID-19 pandemic (1-3). Public health workers might be at similar risk for negative mental health consequences because of the prolonged demand for responding to the pandemic and for implementing an unprecedented vaccination campaign. The extent of mental health conditions among public health workers during the COVID-19 pandemic, however, is uncertain. A 2014 survey estimated that there were nearly 250,000 state and local public health workers in the United States (4). To evaluate mental health conditions among these workers, a nonprobability-based online survey was conducted during March 29-April 16, 2021, to assess symptoms of depression, anxiety, post-traumatic stress disorder (PTSD), and suicidal ideation among public health workers in state, tribal, local, and territorial public health departments. Among 26,174 respondents, 52.8% reported symptoms of at least one mental health condition in the preceding 2 weeks, including depression (30.8%), anxiety (30.3%), PTSD (36.8%), or suicidal ideation (8.4%). The highest prevalence of symptoms of a mental health condition was among respondents aged ≤29 years (range = 13.6%-47.4%) and transgender or nonbinary persons (i.e., those who identified as neither male nor female) of all ages (range = 30.4%-65.5%). Public health workers who reported being unable to take time off from work were more likely to report adverse mental health symptoms. Severity of symptoms increased with increasing weekly work hours and percentage of work time dedicated to COVID-19 response activities. Implementing prevention and control practices that eliminate, reduce, and manage factors that cause or contribute to public health workers' poor mental health might improve mental health outcomes during emergencies. |
Household Surveillance for Norovirus Gastroenteritis in a Nicaraguan Birth Cohort: A Nested Case-Control Analysis of Norovirus Risk Factors.
Vielot NA , Zepeda O , Reyes Y , González F , Vinjé J , Becker-Dreps S , Bucardo F . Pathogens 2023 12 (3) Norovirus causes a large proportion of pediatric acute gastroenteritis (AGE) worldwide, and no vaccines are currently available. To inform public health measures against norovirus gastroenteritis, we assessed risk factors in a case-control study nested in a birth cohort study in Nicaragua. Between June 2017 and January 2022, we followed children weekly for AGE episodes, and collected stool specimens from symptomatic children. Risk factors for AGE were collected during routine weekly visits. Norovirus was detected in stools using real-time reverse transcriptase polymerase chain reaction and positive specimens were genotyped using Sanger sequencing. We included 40 norovirus-positive AGE children matched 1:2 to controls and conducted bivariate and multivariable analyses of norovirus AGE risk factors. Among typeable norovirus infections, GII.4 were more severe than non-GII.4 (four/twenty-one vs. one/nine) and accounted for all emergency visits and hospitalizations. Adjusted conditional logistic regression found that female sex and higher length-for-age Z score were protective against norovirus AGE; a dirt floor in the home, sharing cups or bottles, and recent contact with someone with AGE symptoms were associated with norovirus AGE, though estimates were highly imprecise. Reducing contact with symptomatic persons and with saliva or other bodily fluids on cups or floors could reduce infant norovirus incidence. |
Sources of variation in estimates of Duchenne and Becker muscular dystrophy prevalence in the United States
Whitehead N , Erickson SW , Cai B , McDermott S , Peay H , Howard JF , Ouyang L . Orphanet J Rare Dis 2023 18 (1) 65 BACKGROUND: Direct estimates of rare disease prevalence from public health surveillance may only be available in a few catchment areas. Understanding variation among observed prevalence can inform estimates of prevalence in other locations. The Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) conducts population-based surveillance of major muscular dystrophies in selected areas of the United States. We identified sources of variation in prevalence estimates of Duchenne and Becker muscular dystrophy (DBMD) within MD STARnet from published literature and a survey of MD STARnet investigators, then developed a logic model of the relationships between the sources of variation and estimated prevalence. RESULTS: The 17 identified sources of variability fell into four categories: (1) inherent in surveillance systems, (2) particular to rare diseases, (3) particular to medical-records-based surveillance, and (4) resulting from extrapolation. For the sources of uncertainty measured by MD STARnet, we estimated each source's contribution to the total variance in DBMD prevalence. Based on the logic model we fit a multivariable Poisson regression model to 96 age-site-race/ethnicity strata. Age accounted for 74% of the variation between strata, surveillance site for 6%, race/ethnicity for 3%, and 17% remained unexplained. CONCLUSION: Variation in estimates derived from a non-random sample of states or counties may not be explained by demographic differences alone. Applying these estimates to other populations requires caution. |
Timing and genotype distribution of symptomatic and asymptomatic sapovirus infections and re-infections in a Nicaraguan birth cohort.
González F , Diez-Valcarce M , Reyes Y , Vielot NA , Toval C , Gutiérrez L , Zepeda O , Cuadra EC , Blandón P , Browne H , Bowman NM , Víchez S , Vinjé J , Becker-Dreps S , Bucardo F . Clin Microbiol Infect 2022 29 (4) 540 e9-540 e15 OBJECTIVES: To characterize the timing and genotype distribution of symptomatic and asymptomatic sapovirus infections and re-infections in a Nicaraguan birth cohort. METHODS: Infants (n = 444) were enrolled at 10-14 days of life and followed weekly until 2 years of age. Stool were collected for each acute gastroenteritis (AGE) episode and routine stool were collected monthly. Stools were tested for sapovirus by RT-qPCR and positive samples were genotyped. RESULTS: A total of 348 children completes 2 years of AGE weekly surveillance, 93 (26.7%) of them experienced sapovirus AGE. Most infections occurred after 5 months of age and mainly the second year of life (62.4%, 58/93) and early in the rainy season. Sapovirus screening in all stools from a subset of 67 children, that consistently provided samples, show sapovirus infections in 27.6% (91/330) of the AGE episode and in 2.9% (39/1350) of the routine stool. In this subset, the median age at the first sapovirus AGE was 11.2 month (95%CI; 9.3 - 15.9), 57% (38/67) experienced re-infections, 19 symptomatic and 19 asymptomatic; on average, sapovirus re-infections were reported 7.2 months after symptomatic and 5.3 after asymptomatic infections. Genogroups GI (64%, 69/108) was the most common detected. Sapovirus GI.1 was more frequently detected in AGE than in routine stools (47.2%, 43/91 vs 25.6%, 10/39; p = 0.005) and re-infection with the same genotype was uncommon. CONCLUSION: The first sapovirus infections occurred around 11 months of age, whereas the median time to symptomatic re-infection was 7.2 months. Re-infections with the same sapovirus genotype were rare during 2 years of life suggesting genotype-specific protection following natural infection. |
An introduction to the Marburg virus vaccine consortium, MARVAC
Cross RW , Longini IM , Becker S , Bok K , Boucher D , Carroll MW , Díaz JV , Dowling WE , Draghia-Akli R , Duworko JT , Dye JM , Egan MA , Fast P , Finan A , Finch C , Fleming TR , Fusco J , Geisbert TW , Griffiths A , Günther S , Hensley LE , Honko A , Hunegnaw R , Jakubik J , Ledgerwood J , Luhn K , Matassov D , Meshulam J , Nelson EV , Parks CL , Rustomjee R , Safronetz D , Schwartz LM , Smith D , Smock P , Sow Y , Spiropoulou CF , Sullivan NJ , Warfield KL , Wolfe D , Woolsey C , Zahn R , Henao-Restrepo AM , Muñoz-Fontela C , Marzi A . PLoS Pathog 2022 18 (10) e1010805 The emergence of Marburg virus (MARV) in Guinea and Ghana triggered the assembly of the MARV vaccine "MARVAC" consortium representing leaders in the field of vaccine research and development aiming to facilitate a rapid response to this infectious disease threat. Here, we discuss current progress, challenges, and future directions for MARV vaccines. |
Association between breastfeeding, host genetic factors, and calicivirus gastroenteritis in a Nicaraguan birth cohort.
Vielot NA , Franois R , Huseynova E , Gonzlez F , Reyes Y , Gutierrez L , Nordgren J , Toval-Ruiz C , Vilchez S , Vinj J , Becker-Dreps S , Bucardo F . PLoS One 2022 17 (10) e0267689 BACKGROUND: Norovirus and sapovirus are important causes of childhood acute gastroenteritis (AGE). Breastfeeding prevents AGE generally; however, it is unknown if breastfeeding prevents AGE caused specifically by norovirus and sapovirus. METHODS: We investigated the association between breastfeeding and norovirus or sapovirus AGE episodes in a birth cohort. Weekly data on breastfeeding and AGE episodes were captured during the first year of life. Stools were collected from children with AGE and tested by RT-qPCR for norovirus and sapovirus. Time-dependent Cox models estimated associations between weekly breastfeeding and time to first norovirus or sapovirus AGE. FINDINGS: From June 2017 to July 2018, 444 newborns were enrolled in the study. In the first year of life, 69 and 34 children experienced a norovirus and a sapovirus episode, respectively. Exclusive breastfeeding lasted a median of 2 weeks, and any breastfeeding lasted a median of 43 weeks. Breastfeeding in the last week did not prevent norovirus (HR: 1.09, 95% CI: 0.62, 1.92) or sapovirus (HR: 1.00, 95% CI: 0.82, 1.21) AGE in a given week, adjusting for household sanitation, consumption of high-risk foods, and mother's and child's histo-blood group phenotypes. Maternal secretor-positive phenotype was protective against norovirus AGE, whereas child's secretor-positive phenotype was a risk factor for norovirus AGE. INTERPRETATION: Exclusive breastfeeding in this population was short-lived, and no conclusions could be drawn about its potential to prevent norovirus or sapovirus AGE. Non-exclusive breastfeeding did not prevent norovirus or sapovirus AGE in the first year of life. However, maternal secretor-positive phenotype was associated with a reduced hazard of norovirus AGE. |
Norovirus Infection in Young Nicaraguan Children Induces Durable and Genotype-Specific Antibody Immunity.
Brewer-Jensen PD , Reyes Y , Becker-Dreps S , González F , Mallory ML , Gutiérrez L , Zepeda O , Centeno E , Vielot N , Diez-Valcarce M , Vinjé J , Baric R , Lindesmith LC , Bucardo F . Viruses 2022 14 (9) There are significant challenges to the development of a pediatric norovirus vaccine, mainly due to the antigenic diversity among strains infecting young children. Characterizing human norovirus serotypes and understanding norovirus immunity in naïve children would provide key information for designing rational vaccine platforms. In this study, 26 Nicaraguan children experiencing their first norovirus acute gastroenteritis (AGE) episode during the first 18 months of life were investigated. We used a surrogate neutralization assay that measured antibodies blocking the binding of 13 different norovirus virus-like particles (VLPs) to histo-blood group antigens (HBGAs) in pre- and post-infection sera. To assess for asymptomatic norovirus infections, stools from asymptomatic children were collected monthly, screened for norovirus by RT-qPCR and genotyped by sequencing. Seroconversion of an HBGA-blocking antibody matched the infecting genotype in 25 (96%) of the 26 children. A subset of 13 (50%) and 4 (15%) of the 26 children experienced monotypic GII and GI seroconversion, respectively, strongly suggesting a type-specific response in naïve children, and 9 (35%) showed multitypic seroconversion. The most frequent pairing in multitypic seroconversion (8/12) were GII.4 Sydney and GII.12 noroviruses, both co-circulating at the time. Blocking antibody titers to these two genotypes did not correlate with each other, suggesting multiple exposure rather than cross-reactivity between genotypes. In addition, GII titers remained consistent for at least 19 months post-infection, demonstrating durable immunity. In conclusion, the first natural norovirus gastroenteritis episodes in these young children were dominated by a limited number of genotypes and induced responses of antibodies blocking binding of norovirus VLPs in a genotype-specific manner, suggesting that an effective pediatric norovirus vaccine likely needs to be multivalent and include globally dominant genotypes. The duration of protection from natural infections provides optimism for pediatric norovirus vaccines administered early in life. |
Immune Imprinting Drives Human Norovirus Potential for Global Spread.
Lindesmith LC , Boshier FAT , Brewer-Jensen PD , Roy S , Costantini V , Mallory ML , Zweigart M , May SR , Conrad H , O'Reilly KM , Kelly D , Celma CC , Beard S , Williams R , Tutill HJ , Becker Dreps S , Bucardo F , Allen DJ , Vinjé J , Goldstein RA , Breuer J , Baric RS . mBio 2022 13 (5) e0186122 Understanding the complex interactions between virus and host that drive new strain evolution is key to predicting the emergence potential of variants and informing vaccine development. Under our hypothesis, future dominant human norovirus GII.4 variants with critical antigenic properties that allow them to spread are currently circulating undetected, having diverged years earlier. Through large-scale sequencing of GII.4 surveillance samples, we identified two variants with extensive divergence within domains that mediate neutralizing antibody binding. Subsequent serological characterization of these strains using temporally resolved adult and child sera suggests that neither candidate could spread globally in adults with multiple GII.4 exposures, yet young children with minimal GII.4 exposure appear susceptible. Antigenic cartography of surveillance and outbreak sera indicates that continued population exposure to GII.4 Sydney 2012 and antigenically related variants over a 6-year period resulted in a broadening of immunity to heterogeneous GII.4 variants, including those identified here. We show that the strongest antibody responses in adults exposed to GII.4 Sydney 2012 are directed to previously circulating GII.4 viruses. Our data suggest that the broadening of antibody responses compromises establishment of strong GII.4 Sydney 2012 immunity, thereby allowing the continued persistence of GII.4 Sydney 2012 and modulating the cycle of norovirus GII.4 variant replacement. Our results indicate a cycle of norovirus GII.4 variant replacement dependent upon population immunity. Young children are susceptible to divergent variants; therefore, emergence of these strains worldwide is driven proximally by changes in adult serological immunity and distally by viral evolution that confers fitness in the context of immunity. IMPORTANCE In our model, preepidemic human norovirus variants harbor genetic diversification that translates into novel antigenic features without compromising viral fitness. Through surveillance, we identified two viruses fitting this profile, forming long branches on a phylogenetic tree. Neither evades current adult immunity, yet young children are likely susceptible. By comparing serological responses, we demonstrate that population immunity varies by age/exposure, impacting predicted susceptibility to variants. Repeat exposure to antigenically similar variants broadens antibody responses, providing immunological coverage of diverse variants but compromising response to the infecting variant, allowing continued circulation. These data indicate norovirus GII.4 variant replacement is driven distally by virus evolution and proximally by immunity in adults. |
First Episodes of Norovirus and Sapovirus Gastroenteritis Protect Against Subsequent Episodes in a Nicaraguan Birth Cohort.
Vielot NA , Reyes Y , Blette B , González F , Toval-Ruiz C , Gutiérrez L , Vilchez S , Diez-Valcarce M , Vinjé J , Becker-Dreps S , Bucardo F . Epidemiology 2022 33 (5) 650-653 BACKGROUND: Norovirus and sapovirus cause a large burden of acute gastroenteritis (AGE) in young children. We assessed protection conferred by norovirus and sapovirus AGE episodes against future episodes. METHODS: Between June 2017 and July 2018, we recruited 444 newborns in León, Nicaragua. Weekly household surveys identified AGE episodes over 36 months, and AGE stools were tested by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) for norovirus genogroup (G)I/GII and sapovirus. We used recurrent-event Cox models and negative control methods to estimate protection conferred by first episodes, controlling for observed and unobserved risk factors, respectively. RESULTS: Sapovirus episodes conferred a 69% reduced hazard of subsequent episodes using the negative control method. Norovirus GI (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.31, 1.3) and GII (HR = 0.20; 95% CI = 0.04, 0.44) episodes also appeared highly protective. Protection against norovirus GII was enhanced following two episodes. CONCLUSIONS: Evidence of natural immunity in early childhood provides optimism for the future success of pediatric norovirus and sapovirus vaccines. |
Post-COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection.
Funk AL , Kuppermann N , Florin TA , Tancredi DJ , Xie J , Kim K , Finkelstein Y , Neuman MI , Salvadori MI , Yock-Corrales A , Breslin KA , Ambroggio L , Chaudhari PP , Bergmann KR , Gardiner MA , Nebhrajani JR , Campos C , Ahmad FA , Sartori LF , Navanandan N , Kannikeswaran N , Caperell K , Morris CR , Mintegi S , Gangoiti I , Sabhaney VJ , Plint AC , Klassen TP , Avva UR , Shah NP , Dixon AC , Lunoe MM , Becker SM , Rogers AJ , Pavlicich V , Dalziel SR , Payne DC , Malley R , Borland ML , Morrison AK , Bhatt M , Rino PB , Beneyto Ferre I , Eckerle M , Kam AJ , Chong SL , Palumbo L , Kwok MY , Cherry JC , Poonai N , Wassem M , Simon NJ , Freedman SB . JAMA Netw Open 2022 5 (7) e2223253 IMPORTANCE: Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children. OBJECTIVES: To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls. EXPOSURE: SARS-CoV-2 detected via nucleic acid testing. MAIN OUTCOMES AND MEASURES: Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. RESULTS: Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]). CONCLUSIONS AND RELEVANCE: In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older. |
Preexisting Heterotypic Ligand-blocking Antibody Does Not Protect Against Genogroup II Norovirus Episodes in Young Children.
Becker-Dreps S , Brewer-Jensen PD , González F , Reyes Y , Mallory ML , Gutiérrez L , Vielot NA , Diez-Valcarce M , Vinjé J , Baric RS , Lindesmith LC , Bucardo F . J Pediatric Infect Dis Soc 2022 11 (10) 459-462 A birth cohort design was used to understand whether heterotypic ligand-blocking norovirus antibodies provide cross-protection within the GII genogroup. We found that almost one-half of children who experienced a norovirus GII episode had preexisting antibodies heterotypic to the infecting genotype; therefore, these antibodies did not provide cross-protection. |
Gut Microbiome Changes Occurring with Norovirus Infection and Recovery in Infants Enrolled in a Longitudinal Birth Cohort in Leon, Nicaragua.
Cannon JL , Seabolt MH , Xu R , Montmayeur A , Suh SH , Diez-Valcarce M , Bucardo F , Becker-Dreps S , Vinjé J . Viruses 2022 14 (7) Noroviruses are associated with one fifth of diarrheal illnesses globally and are not yet preventable with vaccines. Little is known about the effects of norovirus infection on infant gut microbiome health, which has a demonstrated role in protecting hosts from pathogens and a possible role in oral vaccine performance. In this study, we characterized infant gut microbiome changes occurring with norovirus-associated acute gastroenteritis (AGE) and the extent of recovery. Metage-nomic sequencing was performed on the stools of five infants participating in a longitudinal birth cohort study conducted in León, Nicaragua. Taxonomic and functional diversities of gut micro-biomes were profiled at time points before, during, and after norovirus infection. Initially, the gut microbiomes resembled those of breastfeeding infants, rich in probiotic species. When disturbed by AGE, Gammaproteobacteria dominated, particularly Pseudomonas species. Alpha diversity in-creased but the genes involved in carbohydrate metabolism and glycan biosynthesis decreased. After the symptoms subsided, the gut microbiomes rebounded with their taxonomic and functional communities resembling those of the pre-infection microbiomes. In this study, during disruptive norovirus-associated AGE, the gut microbiome was temporarily altered, returning to a pre-infection composition a median of 58 days later. Our study provides new insights for developing probiotic treatments and furthering our understanding of the role that episodes of AGE have in shaping the infant gut microbiome, their long-term outcomes, and implications for oral vaccine effectiveness. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. |
Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission.
Karthikeyan S , Levy JI , De Hoff P , Humphrey G , Birmingham A , Jepsen K , Farmer S , Tubb HM , Valles T , Tribelhorn CE , Tsai R , Aigner S , Sathe S , Moshiri N , Henson B , Mark AM , Hakim A , Baer NA , Barber T , Belda-Ferre P , Chacón M , Cheung W , Cresini ES , Eisner ER , Lastrella AL , Lawrence ES , Marotz CA , Ngo TT , Ostrander T , Plascencia A , Salido RA , Seaver P , Smoot EW , McDonald D , Neuhard RM , Scioscia AL , Satterlund AM , Simmons EH , Abelman DB , Brenner D , Bruner JC , Buckley A , Ellison M , Gattas J , Gonias SL , Hale M , Hawkins F , Ikeda L , Jhaveri H , Johnson T , Kellen V , Kremer B , Matthews G , McLawhon RW , Ouillet P , Park D , Pradenas A , Reed S , Riggs L , Sanders A , Sollenberger B , Song A , White B , Winbush T , Aceves CM , Anderson C , Gangavarapu K , Hufbauer E , Kurzban E , Lee J , Matteson NL , Parker E , Perkins SA , Ramesh KS , Robles-Sikisaka R , Schwab MA , Spencer E , Wohl S , Nicholson L , McHardy IH , Dimmock DP , Hobbs CA , Bakhtar O , Harding A , Mendoza A , Bolze A , Becker D , Cirulli ET , Isaksson M , Schiabor Barrett KM , Washington NL , Malone JD , Schafer AM , Gurfield N , Stous S , Fielding-Miller R , Garfein RS , Gaines T , Anderson C , Martin NK , Schooley R , Austin B , MacCannell DR , Kingsmore SF , Lee W , Shah S , McDonald E , Yu AT , Zeller M , Fisch KM , Longhurst C , Maysent P , Pride D , Khosla PK , Laurent LC , Yeo GW , Andersen KG , Knight R . Nature 2022 609 (7925) 101-108 As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases(1-3). SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing(4,5). Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. |
Role Attainment in Emerging Adulthood: Subjective Evaluation by Male Adolescents and Adults with Duchenne and Becker Muscular Dystrophy1.
Peay HL , Do BT , Khosla N , Paramsothy P , Erickson SW , Lamb MM , Whitehead N , Fox DJ , Pandya S , Kinnett K , Wolff J , Howard JF . J Neuromuscul Dis 2022 9 (3) 447-456 BACKGROUND: Youth with Duchenne and Becker muscular dystrophy (DBMD) experience challenges in attaining adult roles, which may impact quality of life. New interventions and treatments may facilitate adult role attainment through improved function. Historical data on adult role attainment is important to assess the impact of new interventions on teens and young adults with DBMD. This study assesses medical knowledge, independence and employment, and relationships among adolescents and young adults with DBMD. METHODS: This study uses data from a 2013 Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) survey on adult transition. Males with DBMD aged 16-30 years were included. RESULTS: Sixty-five of 258 eligible males participated; we report results on 60 participants with an MD STARnet case definition of DMD or BMD. Individuals with BMD reported higher rates than those with DMD of frequently staying home without supervision (50% BMD; 14% DMD), independently performing daily physical needs (93% BMD; 7% DMD) and being employed full or part time (33% BMD; 4% DMD). Most participants understood medication and physical therapy goals; less than half indicated being often or always responsible for scheduling DMBD-related management and refilling medications. Most had not been in a romantic relationship but reported desiring such relationships. CONCLUSIONS: Our data reinforce the impact of DMD (and to a lesser extent, BMD) on transition to adult roles. These results provide an important historical comparator for teen and adult patients who are trying new interventions and therapies. Such data are important for assessing the quality-of-life impact of new treatments and to inform support and training programs for people with DBMD as they transition to new adult roles and responsibilities. |
Outcomes of SARS-CoV-2-Positive Youths Tested in Emergency Departments: The Global PERN-COVID-19 Study.
Funk AL , Florin TA , Kuppermann N , Tancredi DJ , Xie J , Kim K , Neuman MI , Ambroggio L , Plint AC , Mintegi S , Klassen TP , Salvadori MI , Malley R , Payne DC , Simon NJ , Yock-Corrales A , Nebhrajani JR , Chaudhari PP , Breslin KA , Finkelstein Y , Campos C , Bergmann KR , Bhatt M , Ahmad FA , Gardiner MA , Avva UR , Shah NP , Sartori LF , Sabhaney VJ , Caperell K , Navanandan N , Borland ML , Morris CR , Gangoiti I , Pavlicich V , Kannikeswaran N , Lunoe MM , Rino PB , Kam AJ , Cherry JC , Rogers AJ , Chong SL , Palumbo L , Angelats CM , Morrison AK , Kwok MY , Becker SM , Dixon AC , Poonai N , Eckerle M , Wassem M , Dalziel SR , Freedman SB . JAMA Netw Open 2022 5 (1) e2142322 IMPORTANCE: Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized. OBJECTIVE: To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED). DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021. EXPOSURES: Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing. MAIN OUTCOMES AND MEASURES: Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death. RESULTS: Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (>99.9%) had index visit outcome data available, 2007 (62.3%) were from the United States, 1694 (52.6%) were male, and 484 (15.0%) had a self-reported chronic illness; the median (IQR) age was 3 (0-10) years. After 14 days of follow-up, 735 children (22.8% [95% CI, 21.4%-24.3%]) were hospitalized, 107 (3.3% [95% CI, 2.7%-4.0%]) had severe outcomes, and 4 children (0.12% [95% CI, 0.03%-0.32%]) died. Characteristics associated with severe outcomes included being aged 5 to 18 years (age 5 to <10 years vs <1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to <18 years vs <1 year: OR, 2.39 [95% CI 1.38-4.14]), having a self-reported chronic illness (OR, 2.34 [95% CI, 1.59-3.44]), prior episode of pneumonia (OR, 3.15 [95% CI, 1.83-5.42]), symptoms starting 4 to 7 days prior to seeking ED care (vs starting 0-3 days before seeking care: OR, 2.22 [95% CI, 1.29-3.82]), and country (eg, Canada vs US: OR, 0.11 [95% CI, 0.05-0.23]; Costa Rica vs US: OR, 1.76 [95% CI, 1.05-2.96]; Spain vs US: OR, 0.51 [95% CI, 0.27-0.98]). Among a subgroup of 2510 participants discharged home from the ED after initial testing and who had complete follow-up, 50 (2.0%; 95% CI, 1.5%-2.6%) were eventually hospitalized and 12 (0.5%; 95% CI, 0.3%-0.8%) had severe outcomes. Compared with hospitalized SARS-CoV-2-negative youths, the risk of severe outcomes was higher among hospitalized SARS-CoV-2-positive youths (risk difference, 3.9%; 95% CI, 1.1%-6.9%). CONCLUSIONS AND RELEVANCE: In this study, approximately 3% of SARS-CoV-2-positive youths tested in EDs experienced severe outcomes within 2 weeks of their ED visit. Among children discharged home from the ED, the risk was much lower. Risk factors such as age, underlying chronic illness, and symptom duration may be useful to consider when making clinical care decisions. |
Evaluation of Candida auris acquisition in U.S. international travelers using a culture-based screening protocol
Turbett SE , Becker M , Belford B , Kelly M , Desrosiers L , Oliver E , Branda JA , Walters M , Walker AT , LaRocque R , Ryan ET . J Travel Med 2021 29 (1) We establish the feasibility of evaluating U.S. international travelers for Candida auris acquisition using a culture-based screening protocol. Corynebacterium auris was not identified in any of the travelers in this small cohort; further study is needed to determine the overall risk and risk factors for travel-associated acquisition. |
Differentiation of Pediatric-Onset Duchenne and Becker Muscular Dystrophy Subphenotypes Using the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet)
Andrews JG , Lamb M , Conway K , Street N , Westfield C , Ciafaloni E , Matthews D , Pandya S . J Neuromuscul Dis 2021 9 (1) 171-178 Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) phenotypes are used to describe disease progression in affected individuals. However, considerable heterogeneity has been observed across and within these two phenotypes, suggesting a spectrum of severity rather than distinct conditions. Characterizing the phenotypes and subphenotypes aids researchers in the design of clinical studies and clinicians in providing anticipatory guidance to affected individuals and their families. Using data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), we used K-means cluster analysis to group phenotypically similar males with pediatric-onset dystrophinopathy. We identified four dystrophinopathy clusters: Classical BMD, Classical DMD, late ambulatory DMD, and severe DMD. The clusters that we identified align with both 'classical' and 'non-classical' dystrophinopathy described in the literature. Individuals with dystrophinopathies have heterogenous clinical presentations that cluster into phenotypically similar groups. Use of clinically-derived phenotyping may provide a clearer understanding of disease trajectories, reduce variability in study results, and prevent exclusion of certain cohorts from analysis. Findings from studying subphenotypes may ultimately improve our ability to predict disease progression. |
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