Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 231 Records) |
Query Trace: Kumar V[original query] |
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Neuroinvasive bacillus cereus infection in immunocompromised hosts: Epidemiologic investigation of 5 patients with acute myeloid leukemia
Little JS , Coughlin C , Hsieh C , Lanza M , Huang WY , Kumar A , Dandawate T , Tucker R , Gable P , Vazquez Deida AA , Moulton-Meissner H , Stevens V , McAllister G , Ewing T , Diaz M , Glowicz J , Winkler ML , Pecora N , Kubiak DW , Pearson JC , Luskin MR , Sherman AC , Woolley AE , Brandeburg C , Bolstorff B , McHale E , Fortes E , Doucette M , Smole S , Bunnell C , Gross A , Platt D , Desai S , Fiumara K , Issa NC , Baden LR , Rhee C , Klompas M , Baker MA . Open Forum Infect Dis 2024 11 (3) ofae048 BACKGROUND: Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia. METHODS: A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates. RESULTS: Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year. CONCLUSIONS: B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen. |
Clinical and laboratory findings of the first imported case of Middle East respiratory syndrome coronavirus to the United States.
Kapoor M , Pringle K , Kumar A , Dearth S , Liu L , Lovchik J , Perez O , Pontones P , Richards S , Yeadon-Fagbohun J , Breakwell L , Chea N , Cohen NJ , Schneider E , Erdman D , Haynes L , Pallansch M , Tao Y , Tong S , Gerber S , Swerdlow D , Feikin DR . Clin Infect Dis 2014 59 (11) 1511-8 BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) was discovered September 2012 in the Kingdom of Saudi Arabia (KSA). The first US case of MERS-CoV was confirmed on 2 May 2014. METHODS: We summarize the clinical symptoms and signs, laboratory and radiologic findings, and MERS-CoV-specific tests. RESULTS: The patient is a 65-year-old physician who worked in a hospital in KSA where MERS-CoV patients were treated. His illness onset included malaise, myalgias, and low-grade fever. He flew to the United States on day of illness (DOI) 7. His first respiratory symptom, a dry cough, developed on DOI 10. On DOI 11, he presented to an Indiana hospital as dyspneic, hypoxic, and with a right lower lobe infiltrate on chest radiography. On DOI 12, his serum tested positive by real-time reverse transcription polymerase chain reaction (rRT-PCR) for MERS-CoV and showed high MERS-CoV antibody titers, whereas his nasopharyngeal swab was rRT-PCR negative. Expectorated sputum was rRT-PCR positive the following day, with a high viral load (5.31 × 10(6) copies/mL). He was treated with antibiotics, intravenous immunoglobulin, and oxygen by nasal cannula. He was discharged on DOI 22. The genome sequence was similar (>99%) to other known MERS-CoV sequences, clustering with those from KSA from June to July 2013. CONCLUSIONS: This patient had a prolonged nonspecific prodromal illness before developing respiratory symptoms. Both sera and sputum were rRT-PCR positive when nasopharyngeal specimens were negative. US clinicians must be vigilant for MERS-CoV in patients with febrile and/or respiratory illness with recent travel to the Arabian Peninsula, especially among healthcare workers. |
Role of pre-farrow natural planned exposure of gilts in shaping the passive antibody response to rotavirus a in piglets
Kumar D , Anderson Reever AV , Pittman JS , Springer NL , Mallen K , Roman-Sosa G , Sangewar N , Casey-Moore MC , Bowen MD , Mwangi W , Marthaler DG . Vaccines (Basel) 2023 11 (12) Natural planned exposure (NPE) remains one of the most common methods in swine herds to boost lactogenic immunity against rotaviruses. However, the efficacy of NPE protocols in generating lactogenic immunity has not been investigated before. A longitudinal study was conducted to investigate the dynamics of genotype-specific antibody responses to different doses (3, 2 and 1) of Rotavirus A (RVA) NPE (genotypes G4, G5, P[7] and P[23]) in gilts and the transfer of lactogenic immunity to their piglets. Group 1 gilts received three doses of NPE at 5, 4 and 3 weeks pre-farrow (WPF), group 2 received two doses at 5 and 3 WPF, group 3 received one dose at 5 WPF, and group 4 received no NPE (control group). VP7 (G4 and G5) and truncated VP4* (P[7] and P[23]) antigens of RVA were expressed in mammalian and bacterial expression systems, respectively, and used to optimize indirect ELISAs to determine antibody levels against RVA in gilts and piglets. In day-0 colostrum samples, group 1 had significantly higher IgG titers compared to the control group for all four antigens, and either significantly or numerically higher IgG titers than groups 2 and 3. Group 1 also had significantly higher colostrum IgA levels than the control group for all antigens (except G4), and either significantly or numerically higher IgA levels compared to groups 2 and 3. In piglet serum, group 1 piglets had higher IgG titers for all four antigens at day 0 than the other groups. Importantly, RVA NPE stimulated antibodies in all groups regardless of the treatment doses and prevented G4, G5, P[7] and P[23] RVA fecal shedding prior to weaning in piglets in the absence of viral challenge. The G11 and P[34] RVA genotypes detected from pre-weaning piglets differed at multiple amino acid positions with parent NPE strains. In conclusion, the results of this study suggest that the group 1 NPE regimen (three doses of NPE) resulted in the highest anti-RVA antibody (IgG and IgA) levels in the colostrum/milk, and the highest IgG levels in piglet serum. |
Cost of acute respiratory illness episode and its determinants among community-dwelling older adults: a four-site cohort study from India
Krishnan A , Shekhawat K , Ortega-Sanchez IR , Kanungo S , Rajkumar P , Bhardwaj SD , Kumar R , Prabhakaran AO , Gopal G , Chakrabarti AK , Purushothaman GKC , Potdar V , Manna B , Gharpure R , Amarchand R , Choudekar A , Lafond KE , Dar L , Bhattacharjee U , Azziz-Baumgartner E , Saha S . BMJ Public Health 2023 1 (1) e000103 INTRODUCTION: Advocacy for the provision of public health resources, including vaccine for the prevention of acute respiratory illnesses (ARIs) among older adults in India, needs evidence on costs and benefits. Using a cohort of community-dwelling adults aged 60 years and older in India, we estimated the cost of ARI episode and its determinants. METHODS: We enrolled 6016 participants in Ballabgarh, Chennai, Kolkata and Pune from July 2018 to March 2020. They were followed up weekly to identify ARI and classified them as acute upper respiratory illness (AURI) or pneumonia based on clinical features based on British Thoracic Society guidelines. All pneumonia and 20% of AURI cases were asked about the cost incurred on medical consultation, investigation, medications, transportation, food and lodging. The cost of services at public facilities was supplemented by WHO-Choosing Interventions that are Cost-Effective(CHOICE) estimates for 2019. Indirect costs incurred by the affected participant and their caregivers were estimated using human capital approach. We used generalised linear model with log link and gamma family to identify the average marginal effect of key determinants of the total cost of ARI. RESULTS: We included 2648 AURI and 1081 pneumonia episodes. Only 47% (range 36%-60%) of the participants with pneumonia sought care. The mean cost of AURI episode was US$13.9, while that of pneumonia episode was US$25.6, with indirect costs comprising three-fourths of the total. The cost was higher among older men by US$3.4 (95% CI: 1.4 to 5.3), those with comorbidities by US$4.3 (95% CI: 2.8 to 5.7) and those who sought care by US$17.2 (95% CI: 15.1 to 19.2) but not by influenza status. The mean per capita annual cost of respiratory illness was US$29.5. CONCLUSION: Given the high community disease and cost burden of ARI, intensifying public health interventions to prevent and mitigate ARI among this fast-growing older adult population in India is warranted. |
Annual (2023) taxonomic update of RNA-directed RNA polymerase-encoding negative-sense RNA viruses (realm Riboviria: kingdom Orthornavirae: phylum Negarnaviricota)
Kuhn JH , Abe J , Adkins S , Alkhovsky SV , Avšič-Županc T , Ayllón MA , Bahl J , Balkema-Buschmann A , Ballinger MJ , Kumar Baranwal V , Beer M , Bejerman N , Bergeron É , Biedenkopf N , Blair CD , Blasdell KR , Blouin AG , Bradfute SB , Briese T , Brown PA , Buchholz UJ , Buchmeier MJ , Bukreyev A , Burt F , Büttner C , Calisher CH , Cao M , Casas I , Chandran K , Charrel RN , Kumar Chaturvedi K , Chooi KM , Crane A , Dal Bó E , Carlos de la Torre J , de Souza WM , de Swart RL , Debat H , Dheilly NM , Di Paola N , Di Serio F , Dietzgen RG , Digiaro M , Drexler JF , Duprex WP , Dürrwald R , Easton AJ , Elbeaino T , Ergünay K , Feng G , Firth AE , Fooks AR , Formenty PBH , Freitas-Astúa J , Gago-Zachert S , Laura García M , García-Sastre A , Garrison AR , Gaskin TR , Gong W , Gonzalez JJ , de Bellocq J , Griffiths A , Groschup MH , Günther I , Günther S , Hammond J , Hasegawa Y , Hayashi K , Hepojoki J , Higgins CM , Hongō S , Horie M , Hughes HR , Hume AJ , Hyndman TH , Ikeda K , Jiāng D , Jonson GB , Junglen S , Klempa B , Klingström J , Kondō H , Koonin EV , Krupovic M , Kubota K , Kurath G , Laenen L , Lambert AJ , Lǐ J , Li JM , Liu R , Lukashevich IS , MacDiarmid RM , Maes P , Marklewitz M , Marshall SH , Marzano SL , McCauley JW , Mirazimi A , Mühlberger E , Nabeshima T , Naidu R , Natsuaki T , Navarro B , Navarro JA , Neriya Y , Netesov SV , Neumann G , Nowotny N , Nunes MRT , Ochoa-Corona FM , Okada T , Palacios G , Pallás V , Papa A , Paraskevopoulou S , Parrish CR , Pauvolid-Corrêa A , Pawęska JT , Pérez DR , Pfaff F , Plemper RK , Postler TS , Rabbidge LO , Radoshitzky SR , Ramos-González PL , Rehanek M , Resende RO , Reyes CA , Rodrigues TCS , Romanowski V , Rubbenstroth D , Rubino L , Runstadler JA , Sabanadzovic S , Sadiq S , Salvato MS , Sasaya T , Schwemmle M , Sharpe SR , Shi M , Shimomoto Y , Kavi Sidharthan V , Sironi M , Smither S , Song JW , Spann KM , Spengler JR , Stenglein MD , Takada A , Takeyama S , Tatara A , Tesh RB , Thornburg NJ , Tian X , Tischler ND , Tomitaka Y , Tomonaga K , Tordo N , Tu C , Turina M , Tzanetakis IE , Maria Vaira A , van den Hoogen B , Vanmechelen B , Vasilakis N , Verbeek M , von Bargen S , Wada J , Wahl V , Walker PJ , Waltzek TB , Whitfield AE , Wolf YI , Xia H , Xylogianni E , Yanagisawa H , Yano K , Ye G , Yuan Z , Zerbini FM , Zhang G , Zhang S , Zhang YZ , Zhao L , Økland AL . J Gen Virol 2023 104 (8) In April 2023, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by one new family, 14 new genera, and 140 new species. Two genera and 538 species were renamed. One species was moved, and four were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV. |
High-level colonization with antibiotic-resistant enterobacterales among individuals in a semi-urban setting in South India: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study
Kumar CPG , Bhatnagar T , Sathya Narayanan G , Swathi SS , Sindhuja V , Siromany VA , VanderEnde D , Malpiedi P , Smith RM , Bollinger S , Babiker A , Styczynski A . Clin Infect Dis 2023 77 S111-7 BACKGROUND: Antimicrobial resistance poses a significant threat to public health globally. We studied the prevalence of colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE), carbapenem-resistant Enterobacterales (CRE), and colistin-resistant Enterobacterales (Col-RE) in hospitals and the surrounding community in South India. METHODS: Adults from 2 hospitals and the catchment community who consented to provide stool specimens were enrolled. Stools were plated on CHROMagar selective for ESCrE, CRE, and Col-RE. Bacterial identification and antibiotic susceptibility testing were done using Vitek 2 Compact and disc diffusion testing. Colistin broth microdilution was performed for a subset of isolates. Prevalence estimates were calculated with 95% confidence intervals (CIs), and differences were compared across populations using the Pearson χ(2) or Fisher exact test. RESULTS: Between November 2020 and March 2022, 757 adults in the community and 556 hospitalized adults were enrolled. ESCrE colonization prevalence was 71.5% (95% CI, 68.1%–74.6%) in the community and 81.8% (95% CI, 78.4%–84.8%) in the hospital, whereas CRE colonization prevalence was 15.1% (95% CI, 12.7%–17.8%) in the community and 22.7% (95% CI, 19.4%–26.3%) in the hospital. Col-RE colonization prevalence was estimated to be 1.1% (95% CI, .5%–2.1%) in the community and 0.5% (95% CI, .2%–1.6%) in the hospital. ESCrE and CRE colonization in hospital participants was significantly higher compared with community participants (P < .001 for both). CONCLUSIONS: High levels of colonization with antibiotic-resistant Enterobacterales were found in both community and hospital settings. This study highlights the importance of surveillance of colonization in these settings for understanding the burden of antimicrobial resistance. |
Improvement in infection prevention and control compliance at the three tertiary hospitals of Sierra Leone following an operational research study
Kamara RZ , Kamara IF , Moses F , Kanu JS , Kallon C , Kabba M , Moffett DB , Fofanah BD , Margao S , Kamara MN , Moiwo MM , Kpagoi Sstk , Tweya HM , Kumar AMV , Terry RF . Trop Med Infect Dis 2023 8 (7) Implementing infection prevention and control (IPC) programmes in line with the World Health Organization's (WHO) eight core components has been challenging in Sierra Leone. In 2021, a baseline study found that IPC compliance in three tertiary hospitals was sub-optimal. We aimed to measure the change in IPC compliance and describe recommended actions at these hospitals in 2023. This was a 'before and after' observational study using two routine cross-sectional assessments of IPC compliance using the WHO IPC Assessment Framework tool. IPC compliance was graded as inadequate (0-200), basic (201-400), intermediate (401-600), and advanced (601-800). The overall compliance scores for each hospital showed an improvement from 'Basic' in 2021 to 'Intermediate' in 2023, with a percentage increase in scores of 16.9%, 18.7%, and 26.9% in these hospitals. There was improved compliance in all core components, with the majority in the 'Intermediate' level for each hospital IPC programme. Recommended actions including the training of healthcare workers and revision of IPC guidelines were undertaken, but a dedicated IPC budget and healthcare-associated infection surveillance remained as gaps in 2023. Operational research is valuable in monitoring and improving IPC programme implementation. To reach the 'Advanced' level, these hospitals should establish a dedicated IPC budget and develop long-term implementation plans. |
Stable Flow-induced Expression of KLK10 Inhibits Endothelial Inflammation and Atherosclerosis (preprint)
Williams D , Mahmoud M , Liu R , Andueza A , Kumar S , Kang DW , Zhang J , Tamargo I , Villa-Roel N , Baek KI , Lee H , An Y , Zhang L , Tate EW , Bagchi P , Pohl J , Mosnier LO , Diamandis EP , Mihara K , Hollenberg MD , Dai Z , Jo H . bioRxiv 2021 2021.08.10.455857 Introduction Atherosclerosis preferentially occurs in arterial regions exposed to disturbed blood flow (d-flow), while regions exposed to stable flow (s-flow) are protected. The proatherogenic and atheroprotective effects of d-flow and s-flow are mediated in part by the global changes in endothelial cell gene expression, which regulates endothelial dysfunction, inflammation, and atherosclerosis. Previously, we identified Kallikrein-Related Peptidase 10 (KLK10, a secreted serine protease) as a flow-sensitive gene in arterial endothelial cells, but its role in endothelial biology and atherosclerosis was unknown.Methods and Results Here, we show that KLK10 is upregulated under s-flow conditions and downregulated under d-flow conditions using in vivo mouse models and in vitro studies with cultured endothelial cells (ECs). Single-cell RNA sequencing (scRNAseq) and scATAC sequencing (scATACseq) study using the partial carotid ligation mouse model showed flow-regulated KLK10 expression at the epigenomic and transcription levels. Functionally, KLK10 protected against d-flow-induced inflammation and permeability dysfunction in human artery ECs (HAECs). Further, treatment of mice in vivo with rKLK10 decreased arterial endothelial inflammation in d-flow regions. Additionally, rKLK10 injection or ultrasound-mediated transfection of KLK10-expressing plasmids inhibited atherosclerosis in ApoE-/- mice. Studies using pharmacological inhibitors and siRNAs revealed that the anti-inflammatory effects of KLK10 were mediated by a Protease Activated Receptors (PAR1/2)-dependent manner. However, unexpectedly, KLK10 did not cleave the PARs. Through a proteomics study, we identified HTRA1 (High-temperature requirement A serine peptidase 1), which bound and cleaved KLK10. Further, siRNA knockdown of HTRA1 prevented KLK10’s anti-inflammatory and barrier protective function in HAECs, suggesting that HTRA1 regulates KLK10 function. Moreover, KLK10 expression was significantly reduced in human coronary arteries with advanced atherosclerotic plaques compared to those with less severe plaques.Conclusion KLK10 is a flow-sensitive endothelial protein and, in collaboration with HTRA1, serves as an anti-inflammatory, barrier-protective, and anti-atherogenic factor.Competing Interest StatementThe authors have declared no competing interest. |
Comparative genomics of the major parasitic worms (preprint)
International Helminth Genomes Consortium , Coghlan Avril , Tyagi Rahul , Cotton James A , Holroyd Nancy , Rosa Bruce A , Tsai Isheng Jason , Laetsch Dominik R , Beech Robin N , Day Tim A , Hallsworth-Pepin Kymberlie , Ke Huei-Mien , Kuo Tzu-Hao , Lee Tracy J , Martin John , Maizels Rick M , Mutowo Prudence , Ozersky Philip , Parkinson John , Reid Adam J , Rawlings Neil D , Ribeiro Diogo M , Seshadri Swapna Lakshmipuram , Stanley Eleanor , Taylor David W , Wheeler Nicolas J , Zamanian Mostafa , Zhang Xu , Allan Fiona , Allen Judith E , Asano Kazuhito , Babayan Simon A , Bah Germanus , Beasley Helen , Bennett Hayley M , Bisset Stewart A , Castillo Estela , Cook Joseph , Cooper Philip J , Cruz-Bustos Teresa , Cuéllar Carmen , Devaney Eileen , Doyle Stephen R , Eberhard Mark L , Emery Aidan , Eom Keeseon S , Gilleard John S , Gordon Daria , Harcus Yvonne , Harsha Bhavana , Hawdon John M , Hill Dolores E , Hodgkinson Jane , Horák Petr , Howe Kevin L , Huckvale Thomas , Kalbe Martin , Kaur Gaganjot , Kikuchi Taisei , Koutsovoulos Georgios , Kumar Sujai , Leach Andrew R , Lomax Jane , Makepeace Benjamin , Matthews Jacqueline B , Muro Antonio , O’Boyle Noel Michael , Olson Peter D , Osuna Antonio , Partono Felix , Pfarr Kenneth , Rinaldi Gabriel , Foronda Pilar , Rollinson David , Gomez Samblas Mercedes , Sato Hiroshi , Schnyder Manuela , Scholz Tomáš , Shafie Myriam , Tanya Vincent N , Toledo Rafael , Tracey Alan , Urban Joseph F , Wang Lian-Chen , Zarlenga Dante , Blaxter Mark L , Mitreva Makedonka , Berriman Matthew . bioRxiv 2017 236539 Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we compare the genomes of 81 nematode and platyhelminth species, including those of 76 parasites. From 1.4 million genes, we identify gene family births and hundreds of large expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We use a wide-ranging in silico screen to identify and prioritise new potential drug targets and compounds for testing. We also uncover lineage-specific differences in core metabolism and in protein families historically targeted for drug development. This is the broadest comparative study to date of the genomes of parasitic and non-parasitic worms. It provides a transformative new resource for the research community to understand and combat the diseases that parasitic worms cause. |
Social Contact Patterns and Implications for Infectious Disease Transmission: A Systematic Review and Meta-Analysis of Contact Surveys (preprint)
Mousa A , Winskill P , Watson OJ , Ratmann O , Monod M , Ajelli M , Diallo A , Dodd PJ , Grijalva CG , Kiti MC , Krishnan A , Kumar R , Kumar S , Kwok KO , Lanata CF , Le Polain de Waroux O , Leung K , Mahikul W , Melegaro A , Morrow CD , Mossong J , Neal EF , Nokes DJ , Pan-Ngum W , Potter GE , Russell FM , Saha S , Sugimoto JD , Wei WI , Wood RR , Wu JT , Zhang J , Walker PG , Whittaker C . medRxiv 2021 BACKGROUND: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. METHODS: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. RESULTS: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. CONCLUSIONS: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. FUNDING: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1). |
Editorial: Emerging SARS-CoV-2 variants: genomic variations, transmission, pathogenesis, clinical impact, and interventions, volume II
Yadav PD , Patil DY , Kumar S , Bergeron E , Rodriguez SE . Front Med (Lausanne) 2023 10 1215309 This Research Topic has focused on subjects such as tracking emerging SARS-CoV-2 variants, detection, isolation, and genomic characterization of emerging variants, transmission, pathogenesis, clinical effects of variants, assessment of COVID-19 vaccination and treatment effectiveness, comparative analysis of SARS-CoV-2 genomic data, and other public health intervention measures. The Research Topic featured 27 articles highlighting the emergence of Omicron variants and their sub-lineages across the globe and their clinical presentations, specifically asymptomatic infections, COVID-19-associated liver injury, and comorbidities such as hypertension, diabetes, and bronchitis. Additionally, a few studies have reported the efficacy of therapeutic drugs in reducing viral load and the significance of vaccination and a booster dose against Omicron variants. Furthermore, the studies on genomic surveillance and evolutionary analysis have demonstrated the emergence of Omicron and its sub-lineages and their characteristic mutations. All these in-depth studies have explored various elements of Omicron, resulting in a comprehensive understanding of this variant. |
Nasal shedding of vaccine viruses after immunization with a Russian-backbone live attenuated influenza vaccine in India
Dar L , Krishnan A , Kumar R , Dhakad S , Choudekar A , Bagga S , Sharma A , Kumar A , Jethani J , Saha S , Amarchand R , Kumar R , Choudhary A , Narayan VV , Gopal G , Lafond KE , Lindstrom S . Influenza Other Respir Viruses 2023 17 (6) e13149 BACKGROUND: We present post-vaccination nasal shedding findings from the phase IV, community-based, triple-blinded RCT conducted to assess efficacy of trivalent LAIV and inactivated influenza vaccines in rural north India. METHODS: Children aged 2-10 years received LAIV or intranasal placebo across 2015 and 2016, as per initial allocation. On days 2 and 4 post-vaccination, trained study nurses collected nasal swabs from randomly selected subset of trial participants based on operational feasibility, accounting for 10.0% and 11.4% of enrolled participants in 2015 and 2016, respectively. Swabs were collected in viral transport medium and transported under cold chain to laboratory for testing by reverse transcriptase real-time polymerase chain reaction. RESULTS: In year 1, on day 2 post-vaccination, 71.2% (74/104) of LAIV recipients shed at least one of vaccine virus strains compared to 42.3% (44/104) on day 4. During year 1, on day 2 post-vaccination, LAIV-A(H1N1)pdm09 was detected in nasal swabs of 12% LAIV recipients, LAIV-A(H3N2) in 41%, and LAIV-B in 59%. In year 2, virus shedding was substantially lower; 29.6% (32/108) of LAIV recipients shed one of the vaccine virus strains on day 2 compared to 21.3% on day 4 (23/108). CONCLUSION: At day 2 post-vaccination in year 1, two-thirds of LAIV recipients were shedding vaccine viruses. Shedding of vaccine viruses varied between strains and was lower in year 2. More research is needed to determine the reason for lower virus shedding and vaccine efficacy for LAIV-A(H1N1)pdm09. |
Illicitly manufactured fentanyl-involved overdose deaths with detected xylazine - United States, January 2019-June 2022
Kariisa M , O'Donnell J , Kumar S , Mattson CL , Goldberger BA . MMWR Morb Mortal Wkly Rep 2023 72 (26) 721-727 In 2022, provisional data indicated that more than two thirds (68%) of the reported 107,081 drug overdose deaths in the United States involved synthetic opioids other than methadone, principally illicitly manufactured fentanyls (IMFs) (1). Xylazine, a nonopioid sedative not approved for human use and with no known antidote, has been increasingly detected in IMF products in the U.S. drug supply* and in IMF-involved overdose deaths (2). Limited studies suggest xylazine can cause central nervous system depression, respiratory depression, bradycardia, and hypotension in humans (3,4); chronic use might lead to severe withdrawal symptoms(†) as well as skin ulcerations (4). This report uses data from CDC's State Unintentional Drug Overdose Reporting System (SUDORS) to describe IMF-involved(§) overdose deaths with and without xylazine detected that occurred during January 2019-June 2022. Among 21 jurisdictions, which included 20 states and the District of Columbia, the monthly percentage of IMF-involved deaths with xylazine detected increased 276%, from 2.9% to 10.9%. Among IMF-involved deaths during January 2021-June 2022 in 32 jurisdictions, xylazine was detected in a higher percentage of jurisdictions in the Northeast U.S. Census Bureau region; listing detected xylazine as a cause of death varied across jurisdictions. Expanded postmortem and illicit drug product testing for xylazine is needed to clarify prevalence in drug supplies; further investigation of xylazine's effects on humans is necessary to characterize morbidity and overdose risk. It is important for overdose prevention and response messages to highlight the potential presence of xylazine in IMF products and emphasize the need for respiratory and cardiovascular support to address the sedative effects of xylazine. |
Body mass index and associated medical expenditures in the US among privately insured individuals aged 2 to 19 years in 2018
Kumar A , Kompaniyets L , Belay B , Pierce SL , Grosse SD , Goodman AB . JAMA Pediatr 2023 IMPORTANCE: Nearly 40% of US youth aged 2 to 19 years do not have a body mass index (BMI) in the healthy weight category. However, there are no recent estimates for BMI-associated expenditures using clinical or claims data. OBJECTIVE: To estimate medical expenditures among US youth across all BMI categories along with sex and age groups. DESIGN, SETTING, PARTICIPANTS: This cross-sectional study used IQVIA's ambulatory electronic medical records (AEMR) data set linked with IQVIA's PharMetrics Plus Claims database from January 2018 through December 2018. Analysis was performed from March 25, 2022, through June 20, 2022. It included a convenience sample of a geographically diverse patient population from AEMR and PharMetrics Plus. The study sample included privately insured individuals with a BMI measurement in 2018 and excluded patients with pregnancy-related visits. EXPOSURE: BMI categories. MAIN OUTCOMES AND MEASURES: Total medical expenditures were estimated using generalized linear model regression with γ distribution and log-link function. For out-of-pocket (OOP) expenditures, a 2-part model was used that included logistic regression to estimate the probability of positive expenditures followed by generalized linear model. Estimates were shown with and without accounting for sex, race and ethnicity, payer type, geographic region, age interacted with sex and BMI categories, and confounding conditions. RESULTS: The sample included 20 876 individuals aged 2 to 19 years; 104 066 were male (50.5%) and the median age was 12 years. Compared with those with healthy weight, total and OOP expenditures were higher for all other BMI categories. Differences in total expenditures were highest for those with severe obesity ($909; 95% CI, $600-$1218) followed by underweight ($671; 95% CI, $286-$1055) compared with healthy weight. Differences in OOP expenditures were highest for those with severe obesity ($121; 95% CI, $86-$155) followed by underweight ($117; 95% CI, $78-$157) compared with healthy weight. Having underweight was associated with higher total expenditures at ages 2 to 5 years and 6 to 11 years by $679 (95% CI, $228-$1129) and $1166 (95% CI, $632-$1700), respectively; having severe obesity was associated with higher total expenditures at ages 2 to 5 years, 6 to 11 years, and 12 to 17 years by $1035 (95% CI, $208-$1863), $821 (95% CI, $414-$1227), and $1088 (95% CI, $594-$1582), respectively. CONCLUSIONS AND RELEVANCE: The study team found medical expenditures to be higher for all BMI categories when compared with those with healthy weight. These findings may indicate potential economic value of interventions or treatments aimed at reducing BMI-associated health risks. |
Implementation of an antibiotic stewardship initiative in a large urgent care network
Stenehjem E , Wallin A , Willis P , Kumar N , Seibert AM , Buckel WR , Stanfield V , Brunisholz KD , Fino N , Samore MH , Srivastava R , Hicks LA , Hersh AL . JAMA Netw Open 2023 6 (5) e2313011 IMPORTANCE: Urgent Care (UC) encounters result in more inappropriate antibiotic prescriptions than other outpatient setting. Few stewardship interventions have focused on UC. OBJECTIVE: To evaluate the effectiveness of an antibiotic stewardship initiative to reduce antibiotic prescribing for respiratory conditions in a UC network. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study conducted in a UC network with 38 UC clinics and 1 telemedicine clinic included 493 724 total UC encounters. The study compared the antibiotic prescribing rates of all UC clinicians who encountered respiratory conditions for a 12-month baseline period (July 1, 2018, through June 30, 2019) with an intervention period (July 1, 2019, through June 30, 2020). A sustainability period (July 1, 2020, through June 30, 2021) was added post hoc. INTERVENTIONS: Stewardship interventions included (1) education for clinicians and patients, (2) electronic health record (EHR) tools, (3) a transparent clinician benchmarking dashboard, and (4) media. Occurring independently but concurrent with the interventions, a stewardship measure was introduced by UC leadership into the quality measures, including a financial incentive. MAIN OUTCOMES AND MEASURES: The primary outcome was the percentage of UC encounters with an antibiotic prescription for a respiratory condition. Secondary outcomes included antibiotic prescribing when antibiotics were not indicated (tier 3 encounters) and first-line antibiotics for acute otitis media, sinusitis, and pharyngitis. Interrupted time series with binomial generalized estimating equations were used to compare periods. RESULTS: The baseline period included 207 047 UC encounters for respiratory conditions (56.8% female; mean [SD] age, 30.0 [21.4] years; 92.0% White race); the intervention period included 183 893 UC encounters (56.4% female; mean [SD] age, 30.7 [20.8] years; 91.2% White race). Antibiotic prescribing for respiratory conditions decreased from 47.8% (baseline) to 33.3% (intervention). During the initial intervention month, a 22% reduction in antibiotic prescribing occurred (odds ratio [OR], 0.78; 95% CI, 0.71-0.86). Antibiotic prescriptions decreased by 5% monthly during the intervention (OR, 0.95; 95% CI, 0.94-0.96). Antibiotic prescribing for tier 3 encounters decreased by 47% (OR, 0.53; 95% CI, 0.44-63), and first-line antibiotic prescriptions increased by 18% (OR, 1.18; 95% CI, 1.09-1.29) during the initial intervention month. Antibiotic prescriptions for tier 3 encounters decreased by an additional 4% each month (OR, 0.96; 95% CI, 0.94-0.98), whereas first-line antibiotic prescriptions did not change (OR, 1.00; 95% CI, 0.99-1.01). Antibiotic prescribing for respiratory conditions remained stable in the sustainability period. CONCLUSIONS AND RELEVANCE: The findings of this quality improvement study indicated that a UC antibiotic stewardship initiative was associated with decreased antibiotic prescribing for respiratory conditions. This study provides a model for UC antibiotic stewardship. |
Initial public health response and interim clinical guidance for the 2019 novel coronavirus outbreak - United States, December 31, 2019-February 4, 2020.
Patel A , Jernigan DB , 2019-nCOV CDC Response Team , Abdirizak Fatuma , Abedi Glen , Aggarwal Sharad , Albina Denise , Allen Elizabeth , Andersen Lauren , Anderson Jade , Anderson Megan , Anderson Tara , Anderson Kayla , Bardossy Ana Cecilia , Barry Vaughn , Beer Karlyn , Bell Michael , Berger Sherri , Bertulfo Joseph , Biggs Holly , Bornemann Jennifer , Bornstein Josh , Bower Willie , Bresee Joseph , Brown Clive , Budd Alicia , Buigut Jennifer , Burke Stephen , Burke Rachel , Burns Erin , Butler Jay , Cantrell Russell , Cardemil Cristina , Cates Jordan , Cetron Marty , Chatham-Stephens Kevin , Chatham-Stevens Kevin , Chea Nora , Christensen Bryan , Chu Victoria , Clarke Kevin , Cleveland Angela , Cohen Nicole , Cohen Max , Cohn Amanda , Collins Jennifer , Conners Erin , Curns Aaron , Dahl Rebecca , Daley Walter , Dasari Vishal , Davlantes Elizabeth , Dawson Patrick , Delaney Lisa , Donahue Matthew , Dowell Chad , Dyal Jonathan , Edens William , Eidex Rachel , Epstein Lauren , Evans Mary , Fagan Ryan , Farris Kevin , Feldstein Leora , Fox LeAnne , Frank Mark , Freeman Brandi , Fry Alicia , Fuller James , Galang Romeo , Gerber Sue , Gokhale Runa , Goldstein Sue , Gorman Sue , Gregg William , Greim William , Grube Steven , Hall Aron , Haynes Amber , Hill Sherrasa , Hornsby-Myers Jennifer , Hunter Jennifer , Ionta Christopher , Isenhour Cheryl , Jacobs Max , Jacobs Slifka Kara , Jernigan Daniel , Jhung Michael , Jones-Wormley Jamie , Kambhampati Anita , Kamili Shifaq , Kennedy Pamela , Kent Charlotte , Killerby Marie , Kim Lindsay , Kirking Hannah , Koonin Lisa , Koppaka Ram , Kosmos Christine , Kuhar David , Kuhnert-Tallman Wendi , Kujawski Stephanie , Kumar Archana , Landon Alexander , Lee Leslie , Leung Jessica , Lindstrom Stephen , Link-Gelles Ruth , Lively Joana , Lu Xiaoyan , Lynch Brian , Malapati Lakshmi , Mandel Samantha , Manns Brian , Marano Nina , Marlow Mariel , Marston Barbara , McClung Nancy , McClure Liz , McDonald Emily , McGovern Oliva , Messonnier Nancy , Midgley Claire , Moulia Danielle , Murray Janna , Noelte Kate , Noonan-Smith Michelle , Nordlund Kristen , Norton Emily , Oliver Sara , Pallansch Mark , Parashar Umesh , Patel Anita , Patel Manisha , Pettrone Kristen , Pierce Taran , Pietz Harald , Pillai Satish , Radonovich Lewis , Reagan-Steiner Sarah , Reel Amy , Reese Heather , Rha Brian , Ricks Philip , Rolfes Melissa , Roohi Shahrokh , Roper Lauren , Rotz Lisa , Routh Janell , Sakthivel Senthil Kumar Sarmiento Luisa , Schindelar Jessica , Schneider Eileen , Schuchat Anne , Scott Sarah , Shetty Varun , Shockey Caitlin , Shugart Jill , Stenger Mark , Stuckey Matthew , Sunshine Brittany , Sykes Tamara , Trapp Jonathan , Uyeki Timothy , Vahey Grace , Valderrama Amy , Villanueva Julie , Walker Tunicia , Wallace Megan , Wang Lijuan , Watson John , Weber Angie , Weinbaum Cindy , Weldon William , Westnedge Caroline , Whitaker Brett , Whitaker Michael , Williams Alcia , Williams Holly , Willams Ian , Wong Karen , Xie Amy , Yousef Anna . Am J Transplant 2020 20 (3) 889-895 This article summarizes what is currently known about the 2019 novel coronavirus and offers interim guidance. |
Use of Nucleic Acid Amplification Testing for Rapid Detection of Mycobacterium tuberculosis Complex Among US Tuberculosis Patients, 2011‒2017.
Kumar V , Dalton TL , Armstrong LR , Whitesell A , Li R , Starks AM . Open Forum Infect Dis 2021 8 (11) ofab528 BACKGROUND: Nucleic acid amplification (NAA) tests rapidly detect Mycobacterium tuberculosis complex directly from clinical specimens, providing valuable results for those evaluated for tuberculosis. METHODS: We analyzed characteristics of cases with NAA testing performed, compared cases with positive and negative NAA test results, and calculated turnaround time and time to treatment for all verified cases reported to the National Tuberculosis Surveillance System in the United States during 2011-2017. RESULTS: Among 67082 verified tuberculosis cases with NAA testing information, 30820 (45.9%) were reported as not having an NAA test performed; the proportion without NAA testing declined annually, from 60.5% in 2011 to 33.6% in 2017. Of 67082 verified cases, 27912 (41.6%) had positive, 8215 (12.2%) had negative, and 135 (0.2%) had indeterminate NAA test results. Among the 33937 cases with an acid-fast bacilli (AFB) smear-positive result, 24093 (70.9%) had an NAA test performed; 11490 of the 30244 (38.0%) with an AFB smear-negative result had an NAA test performed. Although sputum was the most common specimen type tested, 79.8% (7023/8804) of nonsputum specimen types had a positive NAA test result. Overall, 63.7% of cases with laboratory testing had NAA test results reported <6 days following specimen collection; for 13891 cases not yet on treatment, median time to treatment after the laboratory report date was 2 days. CONCLUSIONS: Our analyses demonstrate increased NAA test utilization between 2011 and 2017. However, a large proportion of cases did not have an NAA test performed, reflecting challenges in broader uptake, suggesting an opportunity to expand use of this diagnostic methodology. |
Malaria outbreak investigation in a tribal area of Pratapgarh district, Rajasthan, India, 2016; Proceedings of 'FETP-ICON 2020' Conference : Chennai, India. 3-5 March 2020
Vaisakh T P , Kumar Rajeev , Mishra Abhishek , Babu Binoy S , Patel Purvi , Dikid Tanzin , Chandra Ramesh , Yadav Rajesh , Papanna Mohan , Velayudhan Anoop , Goel Saurabh , Dhandore Suhas , Shewale Ajit , Ponnaiah Manickam , Murhekar Manoj , Prasad Ravindra , Jain SK , Singh Sujeet . BMC Proc 2021 15 17 Acute encephalopathy syndrome (AES) is characterized by sudden onset of seizures and altered sensorium of infectious or non-infectious origin. Seasonal outbreaks of fatal hypoglycaemic AES in children, associated with eating fruit from the Sapindaceae family (e.g., ackee, litchi), have been reported globally [1,2]. Since 1995, AES outbreaks have been reported during the litchi-harvesting season from May–July in Muzaffarpur, the largest commercial litchi-producing district of Bihar, India [3]. An AES outbreak investigation in Muzaffarpur in 2014 linked known toxins hypoglycin A and α-methylene cyclopropyl glycine (MCPG) in litchi fruit to hypoglycaemic AES in children [3]. Following the 2014 outbreak, the Government of Bihar implemented community-based interventions to prevent hypoglycemia in children. They also strengthened the clinical management of hypoglycaemic seizures in public health facilities [4]. The number of AES cases and deaths declined from 2015–18, suggesting that the interventions were effective. However, in May–June 2019, AES cases increased. We conducted a descriptive epidemiological analysis of the AES cases. | | Methods | | We identified AES cases from established hospital-based surveillance in the two tertiary referral hospitals in Muzaffarpur. We defined a suspected AES case as seizures or altered sensorium in a child aged ≤15 years admitted from 1 May to 2nd July 2019. We excluded patients aged six months to 6 years who were admitted for fever and a single generalized convulsion of <15 minutes in duration and recovered consciousness within 60 minutes of seizure. We conducted a review of medical records and abstracted data using a structured tool for socio-demographics, clinical history, duration of hospitalization, treatment, and laboratory profile. We also assembled a prospective cohort of probable cases admitted to the hospital during the investigation. We defined a probable AES case as new-onset seizures or altered sensorium of <7 days duration in a child aged ≤15 years admitted t from 1 May to 2 July 2019. For the cohort of probable cases, we interviewed the caregivers using a structured clinical-epidemiological questionnaire for socio-demographics, anthropometry, illness characteristics, treatment-seeking behavior, meal assessment, exposure to litchi fruit, and exposure to health messages. For anthropometry, we calculated Z-scores using the World Health Organization 2006 standardized growth tables [5]. | | Results | | Of the 655 suspected and probable AES cases identified, the case fatality rate (CFR) was 21% (139 deaths). The median age was four years (interquartile range: 3 months–14 years), and 58% (378) were females. The first case was reported on 5 May 2019, cases peaked on 15 June, and the last case on 2 July (Figure 1). Among cases with available data, 75% (389/518) had blood glucose levels of <70 mg/dL upon hospital admission, and 75% (476/638) were residents of Muzaffarpur district. We identified cases from 15 (94%) of 16 blocks in the Muzaffarpur district and calculated a district incidence of 22 per 100,000 children ≤15 years old. | | The prospective cohort comprised 94 probable AES cases; CFR was 26%. Among probable cases, 63% (49/78) of caregivers were wage workers, and 34% (31/91) were of low socioeconomic status. Symptoms were reported in the early morning (3 am to 8 am) for 67% (62/93) of cases, and 97% (90/93) presented with seizures. Among probable cases with anthropometry data, 62% (43/69) were underweight (i.e., weight-for-age Z score <-2), 44% (25/57) stunted (i.e., height-for-age Z score <-2), and 43% (10/23) wasted (i.e., weight-for-height Z score <-2). Primary health facilities referred 46% (43/93) of probable cases to the two tertiary hospitals for admission. Among cases referred, only 30% (13/43) received hypoglycemia and seizure management at the primary health facility. | | Eating litchis in the 24 hours and seven days before illness onset was reported by 57% (54/94) and 87% (59/68) of caregivers, respectively. Skipping any meal and skipping the evening meal in the 24 hours before illness onset was reported by 55% (48/88) and 44% (28/63) of caregivers, respectively. Among probable cases, 45% (27/60) of caregivers reported Government Supplementary Nutrition (GSN) programme enrollment. Sixty percent (50/83) of caregivers said a visit by health workers in the week before illness. Still, only 8% (7/83) reported receiving messages on AES prevention and early treatment by health workers in the past month. | | Conclusions | | The 2019 AES outbreak in Muzaffarpur district, Bihar, occurred among young children with hypoglycemia upon hospital admission and had high associated mortality. Although the Government of Bihar implemented community and clinical measures to prevent AES cases after the 2014 outbreak, a large proportion of the AES cases did not benefit from the prevention measures based on our investigation [4]. New state and district health leadership, turnover of community and facility-level healthcare workers, lack of ongoing training and focused community outreach, and competing health priorities might have been factors responsible for the resurgence. To prevent future AES cases, we recommended prompt emergency management of hypoglycemia and seizures at primary health facilities before referral. We recommend enrollment of all eligible children to GSN and enhanced community health communications to reinforce the importance of an evening meal for children and limiting the eating of litchi fruit during the harvesting season from May to July |
Estimating the Direct Medical Costs and Productivity Loss of Outpatient Chlamydia and Gonorrhea Treatment
Kumar S , Chesson H , Gift TL . Sex Transm Dis 2021 48 (2) e18-e21 We used 2016-2017 administrative claims data to calculate the direct medical cost and productivity loss per diagnosed case of chlamydia and gonorrhea treatment. In 2018 US dollars, the direct cost per diagnosed case was $151 for chlamydia (n = 9180) and $85 for gonorrhea (n = 3048); productivity loss was $206 (n = 31) and $246 (n = 7), respectively, among those missing work seeking care. |
Estimating the Direct Medical Outpatient Costs of Diagnosis and Treatment of Trichomoniasis Among Commercially Insured Patients in the United States, 2016 to 2018
Kumar S , Chesson H , Gift TL . Sex Transm Dis 2021 48 (3) e45-e47 We used 2016-2018 outpatient claims data to calculate direct outpatient medical costs per case of trichomoniasis in 2019 US dollars. The outpatient, drug, and total costs per treated case of trichomoniasis were $174, $39, and $213, respectively. Total costs were higher for female patients ($220) than for male patients ($158). |
Comparative genomics of the major parasitic worms
International Helminth Genomes Consortium , Coghlan Avril , Tyagi Rahul , Cotton James A , Holroyd Nancy , Rosa Bruce A , Tsai Isheng Jason , Laetsch Dominik R , Beech Robin N , Day Tim A , Hallsworth-Pepin Kymberlie , Ke Huei-Mien , Kuo Tzu-Hao , Lee Tracy J , Martin John , Maizels Rick M , Mutowo Prudence , Ozersky Philip , Parkinson John , Reid Adam J , Rawlings Neil D , Ribeiro Diogo M , Seshadri Swapna Lakshmipuram , Stanley Eleanor , Taylor David W , Wheeler Nicolas J , Zamanian Mostafa , Zhang Xu , Allan Fiona , Allen Judith E , Asano Kazuhito , Babayan Simon A , Bah Germanus , Beasley Helen , Bennett Hayley M , Bisset Stewart A , Castillo Estela , Cook Joseph , Cooper Philip J , Cruz-Bustos Teresa , Cuéllar Carmen , Devaney Eileen , Doyle Stephen R , Eberhard Mark L , Emery Aidan , Eom Keeseon S , Gilleard John S , Gordon Daria , Harcus Yvonne , Harsha Bhavana , Hawdon John M , Hill Dolores E , Hodgkinson Jane , Horák Petr , Howe Kevin L , Huckvale Thomas , Kalbe Martin , Kaur Gaganjot , Kikuchi Taisei , Koutsovoulos Georgios , Kumar Sujai , Leach Andrew R , Lomax Jane , Makepeace Benjamin , Matthews Jacqueline B , Muro Antonio , O’Boyle Noel Michael , Olson Peter D , Osuna Antonio , Partono Felix , Pfarr Kenneth , Rinaldi Gabriel , Foronda Pilar , Rollinson David , Gomez Samblas Mercedes , Sato Hiroshi , Schnyder Manuela , Scholz Tomáš , Shafie Myriam , Tanya Vincent N , Toledo Rafael , Tracey Alan , Urban Joseph F , Wang Lian-Chen , Zarlenga Dante , Blaxter Mark L , Mitreva Makedonka , Berriman Matthew . Nat Genet 2019 51 (1) 163-174 Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms. |
Editorial: Emerging SARS-CoV-2 variants: Genomic variations, transmission, pathogenesis, clinical impact and interventions
Yadav PD , Kumar S , Bergeron É , Flora MS . Front Med (Lausanne) 2023 10 1178696 Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) originated in Wuhan in December 2019 and rapidly spread across the globe, with the World Health Organization (WHO) declaring it a pandemic in March 2020. Since early 2021, multiple SARS-CoV-2 variants have emerged in various countries around the world (1). Among these, the “Variant of Concern” has been reported to be highly transmissible, infectious, and capable of evading the natural or vaccine-induced immune response. The rapid spread of these variants has resulted in a daily increase in SARS-CoV-2 cases, which are associated with severe morbidity and mortality, exacerbating the pandemic situation (2). The newly emerged variants have become a serious threat to the global COVID-19 vaccination program due to their reduced susceptibility to currently available vaccines (3). It is critical to conduct active genomic surveillance of SARS-CoV-2 variants in order to better understand their transmission, pathogenesis, and the efficacy of vaccines and other therapeutics against these variants. |
Retaining patients with drug-resistant tuberculosis on treatment during the COVID-19 pandemic - Dharavi, Mumbai, India, 2020-2022
Gomare MD , Bhide S , Deshmukh R , Kaipilyawar S , Puri V , Moonan PK , Khetade DK , Nyendak M , Yeldandi V , Smith JP , Tobias JL , Date A , Joshi R , Kumar R , Ho CS . MMWR Morb Mortal Wkly Rep 2023 72 (12) 304-308 Mumbai, India's second largest city, has one of the highest prevalences of drug-resistant tuberculosis* (DRTB) in the world. Treatment for DRTB takes longer and is more complicated than treatment for drug-susceptible tuberculosis (TB). Approximately 300 persons receive a new DRTB diagnosis each year in Mumbai's Dharavi slum(†); historically, fewer than one half of these patients complete DRTB treatment. As nationwide restrictions to mitigate the COVID-19 pandemic were implemented, a program to facilitate uninterrupted DRTB care for patients receiving treatment was also implemented. A comprehensive tool and risk assessment provided support to DRTB patients and linked those who relocated outside of Dharavi during the pandemic to DRTB care at their destination. During May 2020-September 2022, a total of 973 persons received DRTB treatment in Dharavi, including 255 (26%) who relocated during treatment. Overall, 25 (3%) DRTB patients were lost to follow-up, a rate substantially lower than the rate before the pandemic (18%). Proactive planning and implementation of simple tools retained patients on treatment during periods of travel restrictions and relocations, improving programmatic outcomes. This approach might aid public health programs serving migrant populations or patients receiving treatment for DRTB during public health emergencies. |
Perceived Hospital Stress, Severe Acute Respiratory Syndrome Coronavirus 2 Activity, and Care Process Temporal Variance During the COVID-19 Pandemic.
Anesi GL , Andrews A , Bai HJ , Bhatraju PK , Brett-Major DM , Broadhurst MJ , Campbell ES , Cobb JP , Gonzalez M , Homami S , Hypes CD , Irwin A , Kratochvil CJ , Krolikowski K , Kumar VK , Landsittel DP , Lee RA , Liebler JM , Lutrick K , Marts LT , Mosier JM , Mukherjee V , Postelnicu R , Rodina V , Segal LN , Sevransky JE , Spainhour C , Srivastava A , Uyeki TM , Wurfel MM , Wyles D , Evans L . Crit Care Med 2023 51 (4) 445-459 OBJECTIVES: The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity. DESIGN: Prospective weekly hospital stress survey, November 2020-June 2022. SETTING: Society of Critical Care Medicine's Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study. SUBJECTS: Thirteen hospitals across seven U.S. health systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% (sd, 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82; p < 0.0001) but only moderately correlated with ED stress (ρ = 0.52; p < 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5-12%), 7% (3-10%), and 4% (2-6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9-14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6-14 wk] after local case peak; p = 0.59) while the resolution of ED stress (median 6 wk [5-6 wk] after local case peak; p = 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge. CONCLUSIONS: During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked. |
Leveraging PEPFAR-supported health information systems for COVID-19 pandemic response
Mirza M , Grant-Greene Y , Valles Mpjs , Joseph P , Juin S , Brice S , Dely P , Clement MGR , Kumar M , Silver M , Wambugu S , Seebregts C , Futerman D , Weissglas F , Muthee V , Blumenthal W , Wuhib T , Yoon S , Rosen DH . Emerg Infect Dis 2022 28 (13) S49-s58 Since 2003, the US President's Emergency Plan for AIDS Relief (PEPFAR) has supported implementation and maintenance of health information systems for HIV/AIDS and related diseases, such as tuberculosis, in numerous countries. As the COVID-19 pandemic emerged, several countries conducted rapid assessments and enhanced existing PEPFAR-funded HIV and national health information systems to support COVID-19 surveillance data collection, analysis, visualization, and reporting needs. We describe efforts at the US Centers for Disease Control and Prevention (CDC) headquarters in Atlanta, Georgia, USA, and CDC country offices that enhanced existing health information systems in support COVID-19 pandemic response. We describe CDC activities in Haiti as an illustration of efforts in PEPFAR countries. We also describe how investments used to establish and maintain standards-based health information systems in resource-constrained settings can have positive effects on health systems beyond their original scope. |
CDC's COVID-19 international vaccine implementation and evaluation program and lessons from earlier vaccine introductions
Soeters HM , Doshi RH , Fleming M , Adegoke OJ , Ajene U , Aksnes BN , Bennett S , Blau EF , Carlton JG , Clements S , Conklin L , Dahlke M , Duca LM , Feldstein LR , Gidudu JF , Grant G , Hercules M , Igboh LS , Ishizumi A , Jacenko S , Kerr Y , Konne NM , Kulkarni S , Kumar A , Lafond KE , Lam E , Longley AT , McCarron M , Namageyo-Funa A , Ortiz N , Patel JC , Perry RT , Prybylski D , Reddi P , Salman O , Sciarratta CN , Shragai T , Siddula A , Sikare E , Tchoualeu DD , Traicoff D , Tuttle A , Victory KR , Wallace A , Ward K , Wong MKA , Zhou W , Schluter WW , Fitter DL , Mounts A , Bresee JS , Hyde TB . Emerg Infect Dis 2022 28 (13) S208-s216 The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions. |
Antiviral Approaches against Influenza Virus.
Kumari R , Sharma SD , Kumar A , Ende Z , Mishina M , Wang Y , Falls Z , Samudrala R , Pohl J , Knight PR , Sambhara S . Clin Microbiol Rev 2023 36 (1) e0004022 Preventing and controlling influenza virus infection remains a global public health challenge, as it causes seasonal epidemics to unexpected pandemics. These infections are responsible for high morbidity, mortality, and substantial economic impact. Vaccines are the prophylaxis mainstay in the fight against influenza. However, vaccination fails to confer complete protection due to inadequate vaccination coverages, vaccine shortages, and mismatches with circulating strains. Antivirals represent an important prophylactic and therapeutic measure to reduce influenza-associated morbidity and mortality, particularly in high-risk populations. Here, we review current FDA-approved influenza antivirals with their mechanisms of action, and different viral- and host-directed influenza antiviral approaches, including immunomodulatory interventions in clinical development. Furthermore, we also illustrate the potential utility of machine learning in developing next-generation antivirals against influenza. |
Angiopoietin-Like4 Is a Novel Marker of COVID-19 Severity.
Bhatraju PK , Morrell ED , Stanaway IB , Sathe NA , Srivastava A , Postelnicu R , Green R , Andrews A , Gonzalez M , Kratochvil CJ , Kumar VK , Hsiang TY , Gale M Jr , Anesi GL , Wyles D , Broadhurst MJ , Brett-Major D , Mukherjee V , Sevransky JE , Landsittel D , Hung C , Altemeier WA , Gharib SA , Uyeki TM , Cobb JP , Liebler JM , Crosslin DR , Jarvik GP , Segal LN , Evans L , Mikacenic C , Wurfel MM . Crit Care Explor 2023 5 (1) e0827 Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak. OBJECTIVES: To assess the role of ANGPTL4 in COVID-19-related outcomes. DESIGN SETTING AND PARTICIPANTS: Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University. MAIN OUTCOMES AND MEASURES: Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4. RESULTS: Higher plasma ANGPTL4 concentrations were significantly associated with worse hospital mortality (adjusted odds ratio per log(2) increase, 1.53; 95% CI, 1.17-2.00; p = 0.002). Higher ANGPTL4 concentrations were also associated with higher proportions of venous thromboembolism and acute respiratory distress syndrome. Longitudinal ANGPTL4 concentrations were significantly different during the first 2 weeks of hospitalization in patients who subsequently died compared with survivors (p for interaction = 8.1 × 10(-5)). Proteomics analysis demonstrated abundance of ANGPTL4 in lung tissue compared with other organs in COVID-19. ANGPTL4 single-nuclear RNA gene expression was significantly increased in pulmonary alveolar type 2 epithelial cells and fibroblasts in COVID-19 lung tissue compared with controls. CONCLUSIONS AND RELEVANCE: ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients. |
Building communities of practice through case-based e-learning to prevent and manage TB among people living with HIV-India
Agarwal R , Agarwal U , Das C , Reddy RA , Pant R , Ho C , Kumar BR , Dabla V , Moonan PK , Nyendak M , Anand S , Puri AK , Mattoo SK , Sachdeva KS , Yeldandi VV , Sarin R . BMC Infect Dis 2022 22 (1) 967 BACKGROUND: Co-management of HIV-TB coinfection remains a challenge globally. Addressing TB among people living with HIV (PLHIV) is a key priority for the Government of India (GoI). In 2016, GoI implemented single-window services to prevent and manage TB in PLHIV. To strengthen HIV-TB service delivery, case-based e-learning was introduced to health care providers at Antiretroviral Therapy centres (ARTc). METHODS: We implemented a hub and spoke model to deliver biweekly, virtual, case-based e-learning at select ARTc (n=115), from four states of India-Delhi, Uttar Pradesh, Andhra Pradesh and Tamil Nadu. We evaluated feasibility and acceptability of case-based e-learning and its impact on professional satisfaction, self-efficacy, knowledge retention using baseline and completion surveys, session feedback, pre-and post-session assessments. We reviewed routine programmatic data and patient outcomes to assess practices among participating ARTc. RESULTS: Between May 2018 and September 2020, 59 sessions were conducted with mean participation of 55 spokes and 152 participants. For 95% and 88% of sessions80% of respondents agreed that topics were clear and relevant to practice, and duration of session was appropriate, respectively. Session participants significantly improved in perceived knowledge, skills and competencies (+8.6%; p=0.025), and technical knowledge (+18.3%; p=0.04) from baseline. Participating ARTc increased TB screening (+4.2%, p<0.0001), TB diagnosis (+2.7%, p<0.0001), ART initiation (+4.3%, p<0.0001) and TB preventive treatment completion (+5.2%, p<0.0001). CONCLUSION: Case-based e-learning is an acceptable and effective modus of capacity building and developing communities of practice to strengthen integrated care. E-learning could address demand for accessible and sustainable continuing professional education to manage complex diseases, and thereby enhance health equity. We recommend expansion of this initiative across the country for management of co-morbidities as well as other communicable and non-communicable diseases to augment the existing capacity building interventions by provide continued learning and routine mentorship through communities of practice. |
Interpreting biomonitoring data: Introducing the international human biomonitoring (i-HBM) working group's health-based guidance value (HB2GV) dashboard.
Nakayama SF , St-Amand A , Pollock T , Apel P , Bamai YA , Barr DB , Bessems J , Calafat AM , Castaño A , Covaci A , Duca RC , Faure S , Galea KS , Hays S , Hopf NB , Ito Y , Jeddi MZ , Kolossa-Gehring M , Kumar E , LaKind JS , López ME , Louro H , Macey K , Makris KC , Melnyk L , Murawski A , Naiman J , Nassif J , Noisel N , Poddalgoda D , Quirós-Alcalá L , Rafiee A , Rambaud L , Silva MJ , Ueyama J , Verner MA , Waras MN , Werry K . Int J Hyg Environ Health 2022 247 114046 Human biomonitoring (HBM) data measured in specific contexts or populations provide information for comparing population exposures. There are numerous health-based biomonitoring guidance values, but to locate these values, interested parties need to seek them out individually from publications, governmental reports, websites and other sources. Until now, there has been no central, international repository for this information. Thus, a tool is needed to help researchers, public health professionals, risk assessors, and regulatory decision makers to quickly locate relevant values on numerous environmental chemicals. A free, on-line repository for international health-based guidance values to facilitate the interpretation of HBM data is now available. The repository is referred to as the "Human Biomonitoring Health-Based Guidance Value (HB2GV) Dashboard". The Dashboard represents the efforts of the International Human Biomonitoring Working Group (i-HBM), affiliated with the International Society of Exposure Science. The i-HBM's mission is to promote the use of population-level HBM data to inform public health decision-making by developing harmonized resources to facilitate the interpretation of HBM data in a health-based context. This paper describes the methods used to compile the human biomonitoring health-based guidance values, how the values can be accessed and used, and caveats with using the Dashboard for interpreting HBM data. To our knowledge, the HB2GV Dashboard is the first open-access, curated database of HBM guidance values developed for use in interpreting HBM data. This new resource can assist global HBM data users such as risk assessors, risk managers and biomonitoring programs with a readily available compilation of guidance values. |
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