Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 87 Records) |
Query Trace: Nair P[original query] |
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Comprehensive Search for Novel Circulating miRNAs and Axon Guidance Pathway Proteins Associated with Risk of End Stage Kidney Disease in Diabetes.
Satake E , Saulnier PJ , Kobayashi H , Gupta MK , Looker HC , Wilson JM , Md Dom ZI , Ihara K , O'Neil K , Krolewski B , Pipino C , Pavkov ME , Nair V , Bitzer M , Niewczas MA , Kretzler M , Mauer M , Doria A , Najafian B , Kulkarni RN , Duffin KL , Pezzolesi MG , Kahn CR , Nelson RG , Krolewski AS . J Am Soc Nephrol 2021 32 (9) 2331-2351 BACKGROUND: Mechanisms underlying the pro gression of diabetic kidney disease to ESKD are not fully understood. METHODS: We performed global microRNA (miRNA) analysis on plasma from two cohorts consisting of 375 individuals with type 1 and type 2 diabetes with late diabetic kidney disease, and targeted proteomics analysis on plasma from four cohorts consisting of 746 individuals with late and early diabetic kidney disease. We examined structural lesions in kidney biopsy specimens from the 105 individuals with early diabetic kidney disease. Human umbilical vein endothelial cells were used to assess the effects of miRNA mimics or inhibitors on regulation of candidate proteins. RESULTS: In the late diabetic kidney disease cohorts, we identified 17 circulating miRNAs, represented by four exemplars (miR-1287-5p, miR-197-5p, miR-339-5p, and miR-328-3p), that were strongly associated with 10-year risk of ESKD. These miRNAs targeted proteins in the axon guidance pathway. Circulating levels of six of these proteins-most notably, EFNA4 and EPHA2-were strongly associated with 10-year risk of ESKD in all cohorts. Furthermore, circulating levels of these proteins correlated with severity of structural lesions in kidney biopsy specimens. In contrast, expression levels of genes encoding these proteins had no apparent effects on the lesions. In in vitro experiments, mimics of miR-1287-5p and miR-197-5p and inhibitors of miR-339-5p and miR-328-3p upregulated concentrations of EPHA2 in either cell lysate, supernatant, or both. CONCLUSIONS: This study reveals novel mechanisms involved in progression to ESKD and points to the importance of systemic factors in the development of diabetic kidney disease. Some circulating miRNAs and axon guidance pathway proteins represent potential targets for new therapies to prevent and treat this condition. |
An evaluation of the ecological niche of Orf virus (Poxviridae): Challenges of distinguishing broad niches from no niches
Nair RR , Nakazawa Y , Peterson AT . PLoS One 2024 19 (1) e0293312 Contagious ecthyma is a skin disease, caused by Orf virus, creating great economic threats to livestock farming worldwide. Zoonotic potential of this disease has gained recent attention owing to the re-emergence of disease in several parts of the world. Increased public health concern emphasizes the need for a predictive understanding of the geographic distributional potential of Orf virus. Here, we mapped the current distribution using occurrence records, and estimated the ecological niche in both geographical and environmental spaces. Twenty modeling experiments, resulting from two- and three-partition models, were performed to choose the candidate models that best represent the geographic distributional potential of Orf virus. For all of our models, it was possible to reject the null hypothesis of predictive performance no better than random expectations. However, statistical significance must be accompanied by sufficiently good predictive performance if a model is to be useful. In our case, omission of known distribution of the virus was noticed in all Maxent models, indicating inferior quality of our models. This conclusion was further confirmed by the independent final evaluation, using occurrence records sourced from the Centre for Agriculture and Bioscience International. Minimum volume ellipsoid (MVE) models indicated the broad range of environmental conditions under which Orf virus infections are found. The excluded climatic conditions from MVEs could not be considered as unsuitable owing to the broad distribution of Orf virus. These results suggest two possibilities: that the niche models fail to identify niche limits that constrain the virus, or that the virus has no detectable niche, as it can be found throughout the geographic distributions of its hosts. This potential limitation of component-based pathogen-only ENMs is discussed in detail. |
Burden of respiratory syncytial virus-associated acute respiratory infections during pregnancy
Kenmoe S , Chu HY , Dawood FS , Milucky J , Kittikraisak W , Matthewson H , Kulkarni D , Suntarattiwong P , Frivold C , Mohanty S , Havers F , Li Y , Nair H . J Infect Dis 2023 INTRODUCTION: With the licensure of maternal RSV vaccines in Europe and USA, data are needed to better characterize the burden of respiratory syncytial virus (RSV)-associated acute respiratory infections (ARI) in pregnancy. This study aims to determine among pregnant individuals the proportion of ARI testing positive for RSV and RSV incidence rate, RSV-associated hospitalizations, deaths, and perinatal outcomes. METHODS: We conducted a systematic review following PRISMA 2020 guidelines using five databases (Medline, Embase, Global Health, Web of Science and Global Index Medicus) and included additional unpublished data. Pregnant individuals with respiratory infections who had respiratory samples tested for RSV were included. We used a random-effects meta-analysis to generate overall proportions and rate estimates across studies. RESULTS: Eleven studies with pregnant individuals recruited between 2010 and 2022 were identified, most of which recruited pregnant individuals in community, inpatient and outpatient settings. Among 8126 pregnant individuals, the proportion with respiratory infections that tested positive for RSV ranged from 0.9% to 10.7%, with a meta-estimate of 3.4% (95% CI: 1.9; 54). The pooled incidence rate of RSV infection episodes among pregnant individuals was 26.0 (15.8; 36.2) per 1000 person-years. RSV hospitalization rates reported in two studies were 2.4 and 3.0 per 1000 person-years. Of five studies that ascertained RSV-associated deaths among 4708 pregnant individuals, no deaths were reported. Three studies comparing RSV-positive and RSV-negative pregnant individuals found no difference in odds of miscarriage, stillbirth, low birth weight, and small for gestational age. RSV-positive pregnant individuals had higher odds of preterm delivery (odds ratio 3.6 [1.3; 10.3]). CONCLUSION: Data on RSV-associated hospitalization incidence rates are limited but available estimates are lower than those reported in older adults and young children. As countries debate whether to include RSV vaccines in maternal vaccination programs, which are primarily intended to protect infants, this information could be useful in shaping vaccine policy decisions. |
Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes
Carey ME , Dyson ZA , Ingle DJ , Amir A , Aworh MK , Chattaway MA , Chew KL , Crump JA , Feasey NA , Howden BP , Keddy KH , Maes M , Parry CM , Van Puyvelde S , Webb HE , Afolayan AO , Alexander AP , Anandan S , Andrews JR , Ashton PM , Basnyat B , Bavdekar A , Bogoch II , Clemens JD , da Silva KE , De A , de Ligt J , Diaz Guevara PL , Dolecek C , Dutta S , Ehlers MM , Francois Watkins L , Garrett DO , Godbole G , Gordon MA , Greenhill AR , Griffin C , Gupta M , Hendriksen RS , Heyderman RS , Hooda Y , Hormazabal JC , Ikhimiukor OO , Iqbal J , Jacob JJ , Jenkins C , Jinka DR , John J , Kang G , Kanteh A , Kapil A , Karkey A , Kariuki S , Kingsley RA , Koshy RM , Lauer AC , Levine MM , Lingegowda RK , Luby SP , Mackenzie GA , Mashe T , Msefula C , Mutreja A , Nagaraj G , Nagaraj S , Nair S , Naseri TK , Nimarota-Brown S , Njamkepo E , Okeke IN , Perumal SPB , Pollard AJ , Pragasam AK , Qadri F , Qamar FN , Rahman SIA , Rambocus SD , Rasko DA , Ray P , Robins-Browne R , Rongsen-Chandola T , Rutanga JP , Saha SK , Saha S , Saigal K , Sajib MSI , Seidman JC , Shakya J , Shamanna V , Shastri J , Shrestha R , Sia S , Sikorski MJ , Singh A , Smith AM , Tagg KA , Tamrakar D , Tanmoy AM , Thomas M , Thomas MS , Thomsen R , Thomson NR , Tupua S , Vaidya K , Valcanis M , Veeraraghavan B , Weill FX , Wright J , Dougan G , Argimón S , Keane JA , Aanensen DM , Baker S , Holt KE . Elife 2023 12 BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]). | Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium’s analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps. | eng |
Notes from the field: Safety monitoring of Novavax COVID-19 vaccine among persons aged 12 years - United States, July 13, 2022-March 13, 2023
Romanson B , Moro PL , Su JR , Marquez P , Nair N , Day B , DeSantis A , Shimabukuro TT . MMWR Morb Mortal Wkly Rep 2023 72 (31) 850-851 The NVX-CoV2373 (Novavax) COVID-19 vaccine is a recombinant spike protein nanoparticle vaccine with Matrix-M adjuvant. Novavax is authorized and recommended as a primary 2-dose monovalent vaccination series in persons aged ≥12 years to prevent COVID-19 and as a monovalent booster dose in persons aged ≥18 years who are unable to or unwilling to receive an mRNA COVID-19 bivalent vaccine (1). | | Top | | Investigation and Outcomes | During July 13, 2022–March 13, 2023, a total of 69,227 Novavax doses were administered to persons aged ≥12 years in the United States, and 230 reports of adverse events (AEs) after Novavax vaccination were received by the Vaccine Adverse Event Reporting System (VAERS) (2). The median age of patients in the reports was 45 years (IQR = 31–61 years); 152 (66.1%) reports concerned females, and 104 (45.2%) concerned non-Hispanic White persons (Table). Within the study period, VAERS received no reports concerning pregnant women. Most VAERS reports (211; 91.7%) were classified as nonserious.* The most commonly reported AEs included dizziness (33; 14.3%), fatigue (26; 11.3%), and headache (25; 10.9%). |
Demographic and co-morbidity characteristics of patients tested for SARS-CoV-2 from March 2020 to January 2022 in a national clinical research network: results from PCORnet (preprint)
Block JP , Marsolo KA , Nagavedu K , Bailey LC , Boehmer TK , Fearrington J , Harris AM , Garrett N , Goodman AB , Gundlapalli AV , Kaushal R , Kho A , McTigue KM , Nair VP , Puro J , Shenkman E , Weiner MG , Williams N , Carton TW . medRxiv 2023 18 Background: Prior studies have documented differences in the age, racial, and ethnic characteristics among patients with SARS-CoV-2 infection. However, little is known about how these characteristics changed over time during the pandemic and whether racial, ethnic, and age disparities evident early in the pandemic were persistent over time. This study reports on trends in SARS-CoV-2 infections among U.S. adults from March 1, 2020 to January, 31 2022, using data from electronic health records. Methods and Findings: We captured repeated cross-sectional information from 43 large healthcare systems in 52 U.S. States and territories, participating in PCORnet, the National Patient-Centered Clinical Research Network. Using distributed queries executed at each participating institution, we acquired information for all patients >= 20 years of age who were tested for SARS-CoV-2 (both positive and negative results), including care setting, age, sex, race, and ethnicity by month as well as comorbidities (assessed with diagnostic codes). During this time period, 1,325,563 patients had positive (13% inpatient) and 6,705,868 patients had negative (25% inpatient) viral tests for SARS-CoV-2. Disparities in testing positive were present across racial and ethnic groups, especially in the inpatient setting. Compared to White patients, Black or African American and other race patients had relative risks for testing positive of 1.5 or greater in the inpatient setting for 12 of the 23-month study period. Compared to non-Hispanic patients, Hispanic patients had relative risks for testing positive in the inpatient setting of 1.5 or greater for 16 of 23. Ethnic and racial differences were present in emergency department and ambulatory settings but were less common across time than in inpatient settings. Trends in infections by age group demonstrated higher test positivity for older patients in the inpatient setting only for most months, except for June and July of 2020, April to August 2021, and January 2022. Comorbidities were common, with much higher rates among those hospitalized; hypertension (38% of patients SARS-CoV-2 positive vs. 29% for those negative) and type 2 diabetes mellitus (22% vs. 13%) were the most common. Conclusion and Relevance: Racial and ethnic disparities changed over time among persons infected with SARS-CoV-2. These trends highlight potential underlying mechanisms, such as poor access to care and differential vaccination rates, that may have contributed to greater disparities, especially early in the pandemic. Monitoring data on characteristics of patients testing positive in real time could allow public health officials and policymakers to tailor interventions to ensure that patients and communities most in need are receiving adequate testing, mitigation strategies, and treatment. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Reporting Rates for VAERS Death Reports Following COVID-19 Vaccination, December 14, 2020-November 17, 2021 (preprint)
Day B , Menschik D , Thompson D , Jankosky C , Su J , Moro P , Zinderman C , Welsh K , Nair N . medRxiv 2022 07 Background: Despite widely available safety information for the COVID-19 vaccines, vaccine hesitancy remains a challenge. In some cases, vaccine hesitancy may be related to concerns about the number of reports of death to the Vaccine Adverse Event Reporting System (VAERS). Objective(s): To provide information and context about reports of death to VAERS following COVID-19 vaccination. Design(s): Descriptive study; reporting rates for VAERS death reports. Setting(s): United States; December 14, 2020, to November 17, 2021. Participant(s): COVID-19 vaccine recipients. Measurements: Reporting rates for death events per million persons vaccinated; adverse event counts; data mining signals of disproportionate reporting. Result(s): 9,201 death events were reported for COVID-19 vaccine recipients aged five years and older (or age unknown). Reporting rates for death events increased with increasing age, and males generally had higher reporting rates than females. For death events within seven days and 42 days of vaccination, respectively, observed reporting rates were lower than the expected all-cause death rates. Reporting rates for Ad26.COV2.S vaccine were generally higher than for mRNA COVID-19 vaccines, but still lower than the expected all-cause death rates. Reported adverse events were nonspecific or reflected the known leading causes of death. Limitation(s): VAERS data are subject to several limitations such as reporting bias (underreporting and stimulated reporting), missing or inaccurate information, and lack of a control group. Reported diagnoses, including deaths, are not causally verified diagnoses. Conclusion(s): Reporting rates for death events were lower than the expected all-cause mortality rates. Trends in reporting rates reflected known trends in background mortality rates. These findings do not suggest an association between vaccination and overall increased mortality. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Value profile for respiratory syncytial virus vaccines and monoclonal antibodies
Fleming JA , Baral R , Higgins D , Khan S , Kochar S , Li Y , Ortiz JR , Cherian T , Feikin D , Jit M , Karron RA , Limaye RJ , Marshall C , Munywoki PK , Nair H , Newhouse LC , Nyawanda BO , Pecenka C , Regan K , Srikantiah P , Wittenauer R , Zar HJ , Sparrow E . Vaccine 2023 41 Suppl 2 S7-S40 Respiratory syncytial virus (RSV) is the predominant cause of acute lower respiratory infection (ALRI) in young children worldwide, yet no licensed RSV vaccine exists to help prevent the millions of illnesses and hospitalizations and tens of thousands of young lives taken each year. Monoclonal antibody (mAb) prophylaxis exists for prevention of RSV in a small subset of very high-risk infants and young children, but the only currently licensed product is impractical, requiring multiple doses and expensive for the low-income settings where the RSV disease burden is greatest. A robust candidate pipeline exists to one day prevent RSV disease in infant and pediatric populations, and it focuses on two promising passive immunization approaches appropriate for low-income contexts: maternal RSV vaccines and long-acting infant mAbs. Licensure of one or more candidates is feasible over the next one to three years and, depending on final product characteristics, current economic models suggest both approaches are likely to be cost-effective. Strong coordination between maternal and child health programs and the Expanded Program on Immunization will be needed for effective, efficient, and equitable delivery of either intervention. This 'Vaccine Value Profile' (VVP) for RSV is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships and multi-lateral organizations, and in collaboration with stakeholders from the WHO headquarters. All contributors have extensive expertise on various elements of the RSV VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information. |
A global genomic analysis of Salmonella Concord reveals lineages with high antimicrobial resistance in Ethiopia
Cuypers WL , Meysman P , Weill FX , Hendriksen RS , Beyene G , Wain J , Nair S , Chattaway MA , Perez-Sepulveda BM , Ceyssens PJ , de Block T , Lee WWY , Pardos de la Gandara M , Kornschober C , Moran-Gilad J , Veldman KT , Cormican M , Torpdahl M , Fields PI , ÄŒerný T , Hardy L , Tack B , Mellor KC , Thomson N , Dougan G , Deborggraeve S , Jacobs J , Laukens K , Van Puyvelde S . Nat Commun 2023 14 (1) 3517 Antimicrobial resistant Salmonella enterica serovar Concord (S. Concord) is known to cause severe gastrointestinal and bloodstream infections in patients from Ethiopia and Ethiopian adoptees, and occasional records exist of S. Concord linked to other countries. The evolution and geographical distribution of S. Concord remained unclear. Here, we provide a genomic overview of the population structure and antimicrobial resistance (AMR) of S. Concord by analysing genomes from 284 historical and contemporary isolates obtained between 1944 and 2022 across the globe. We demonstrate that S. Concord is a polyphyletic serovar distributed among three Salmonella super-lineages. Super-lineage A is composed of eight S. Concord lineages, of which four are associated with multiple countries and low levels of AMR. Other lineages are restricted to Ethiopia and horizontally acquired resistance to most antimicrobials used for treating invasive Salmonella infections in low- and middle-income countries. By reconstructing complete genomes for 10 representative strains, we demonstrate the presence of AMR markers integrated in structurally diverse IncHI2 and IncA/C2 plasmids, and/or the chromosome. Molecular surveillance of pathogens such as S. Concord supports the understanding of AMR and the multi-sector response to the global AMR threat. This study provides a comprehensive baseline data set essential for future molecular surveillance. |
Evaluation of the impact of guideline communication from the Centers for Disease Control and Prevention and the Centers for Medicare and Medicaid Services among US healthcare providers: COVID-19 prevention counselling guidance
Taylor MM , Deb A , Frazier B , Lueken JR , Das M , Molke J , Fitzgerald E , Ullian T , Nair R , Couch M , Turbyfill C , Horter L , Joshi C , DeLuca N . Nurs Open 2023 10 (11) 7437-7445 AIM: To evaluate healthcare provider awareness and uptake of the Centers for Medicare & Medicaid Services (CMS) billing for coronavirus disease 2019 (COVID-19) prevention counselling and the delivery of prevention counselling to patients awaiting severe acute respiratory syndrome coronavirus 2 test results. DESIGN: Cross sectional survey of US-based healthcare providers in February 2021. METHODS: Analysis of associations with healthcare provider-reported awareness of CMS prevention counselling guidance and billing with provider type, specialty, and work setting. RESULTS: A total of 1919 healthcare providers responded to the survey. Overall, 38% (726/1919) of providers reported awareness of available CMS reimbursement for COVID-19 patient counselling and 29% (465/1614) of CMS billing-eligible providers reported billing for this counselling. Among physicians, those aware of CMS guidance were significantly more likely to bill (58%) versus those unaware (10%). Among RNSights respondents eligible for CMS billing (n = 114), 31% of those aware of the guidance reported billing as compared to 0% of those not aware. |
COVID-19 vaccine safety first year findings in adolescents
Hesse EM , Hause A , Myers T , Su JR , Marquez P , Zhang B , Cortese MM , Thames-Allen A , Curtis CR , Maloney SA , Thompson D , Nair N , Alimchandani M , Niu M , Gee J , Shay DK , Shimabukuro TT . Pediatrics 2023 151 (5) BACKGROUND AND OBJECTIVES: The Food and Drug Administration expanded Emergency Use Authorization for use of Pfizer-BioNTech (BNT-162b2) coronavirus disease 2019 vaccine to include people ages 12 years and older on May 10, 2021. We describe adverse events observed during the first full year of the US coronavirus disease 2019 vaccination program for adolescents ages 12 to 17 years. METHODS: We conducted descriptive analyses using data from 2 complementary US vaccine safety monitoring systems: v-safe, a voluntary smartphone-based system that monitors reactions and health impacts, and the Vaccine Adverse Event Reporting System (VAERS), the national spontaneous reporting system. We reviewed reports and calculated adverse event reporting rates using vaccine administration data. RESULTS: Among 172 032 adolescents ages 12 to 17 years enrolled in v-safe, most reported reactions following BNT-162b2 were mild to moderate, most frequently reported on the day after vaccination, and more common after dose 2. VAERS received 20 240 adverse event reports; 91.5% were nonserious. Among adverse events of interest, we verified 40 cases of multisystem inflammation syndrome in children (1.2 cases per million vaccinations), 34 (85%) of which had evidence of prior severe acute respiratory syndrome coronavirus 2 infection; and 570 cases of myocarditis (17.7 cases per million vaccinations), most of whom (77%) reported symptom resolution at the time of report. CONCLUSIONS: During the first year BNT-162b2 was administered to adolescents ages 12 to 17 years, most reported adverse events were mild and appeared self-limited. Rates of myocarditis were lower than earlier reports. No new serious safety concerns were identified. |
In-hospital mortality risk stratification in children under 5 years old with pneumonia with or without pulse oximetry: A secondary analysis of the Pneumonia REsearch Partnership To Assess WHO REcommendations (PREPARE) dataset
Hooli S , King C , McCollum ED , Colbourn T , Lufesi N , Mwansambo C , Gregory CJ , Thamthitiwat S , Cutland C , Madhi SA , Nunes MC , Gessner BD , Hazir T , Mathew JL , Addo-Yobo E , Chisaka N , Hassan M , Hibberd PL , Jeena P , Lozano JM , MacLeod WB , Patel A , Thea DM , Nguyen NTV , Zaman SM , Ruvinsky RO , Lucero M , Kartasasmita CB , Turner C , Asghar R , Banajeh S , Iqbal I , Maulen-Radovan I , Mino-Leon G , Saha SK , Santosham M , Singhi S , Awasthi S , Bavdekar A , Chou M , Nymadawa P , Pape JW , Paranhos-Baccala G , Picot VS , Rakoto-Andrianarivelo M , Rouzier V , Russomando G , Sylla M , Vanhems P , Wang J , Basnet S , Strand TA , Neuman MI , Arroyo LM , Echavarria M , Bhatnagar S , Wadhwa N , Lodha R , Aneja S , Gentile A , Chadha M , Hirve S , O'Grady KF , Clara AW , Rees CA , Campbell H , Nair H , Falconer J , Williams LJ , Horne M , Qazi SA , Nisar YB . Int J Infect Dis 2023 129 240-250 OBJECTIVES: We determined pulse oximetry benefit in pediatric pneumonia mortality-risk stratification and chest indrawing pneumonia in-hospital mortality risk factors. METHODS: We report characteristics and in-hospital pneumonia-related mortality of children 2-59-months-old included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest indrawing pneumonia to identify mortality risk factors. RESULTS: Among 285,839 children, 164,244 (57·5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5·8%, 95% CI 5·6-5·9% vs 2·1%, 95% CI 1·9-2·4%). One in five children with chest indrawing pneumonia was hypoxemic (19·7%, 95% CI 19·0-20·4%) and the hypoxemic CFR was 10·3% (95% CI 9·1%-11·5%). Other mortality risk factors were younger age (either 2-5 months (aOR 9·94, 95% CI 6·67-14·84) or 6-11 months (aOR 2·67, 95% CI 1·71-4·16)), moderate malnutrition (aOR 2·41, 95% CI 1·87-3·09), and female sex (aOR 1·82, 95% CI 1·43-2·32). CONCLUSIONS: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest indrawing pneumonia were hypoxemic and one in ten died. Young age and moderate malnutrition were risk factors for in-hospital chest indrawing pneumonia-related mortality. Pulse oximetry should be integrated in under-five pneumonia hospital care. |
Reporting rates for VAERS death reports following COVID-19 vaccination, December 14, 2020-November 17, 2021
Day B , Menschik D , Thompson D , Jankosky C , Su J , Moro P , Zinderman C , Welsh K , Dimova RB , Nair N . Pharmacoepidemiol Drug Saf 2023 32 (7) 763-772 PURPOSE: Despite widely available safety information for the COVID-19 vaccines, vaccine hesitancy remains a challenge. In some cases, vaccine hesitancy may be related to concerns about the number of reports of death to the Vaccine Adverse Event Reporting System (VAERS). We aimed to provide information and context about reports of death to VAERS following COVID-19 vaccination. METHODS: This is a descriptive study evaluating reporting rates for VAERS death reports for COVID-19 vaccine recipients in the United States between December 14, 2020, and November 17, 2021. Reporting rates were calculated as death events per million persons vaccinated and compared to expected all-cause (background) death rates. RESULTS: 9,201 death events were reported for COVID-19 vaccine recipients aged five years and older (or age unknown). Reporting rates for death events increased with increasing age, and males generally had higher reporting rates than females. For death events within seven days and 42 days of vaccination, respectively, observed reporting rates were lower than the expected all-cause death rates. Reporting rates for Ad26.COV2.S vaccine were generally higher than for mRNA COVID-19 vaccines, but still lower than the expected all-cause death rates. Limitations of VAERS data include potential reporting bias, missing or inaccurate information, lack of a control group, and reported diagnoses, including deaths, are not causally verified diagnoses. CONCLUSIONS: Reporting rates for death events were lower than the all-cause death rates expected in the general population. Trends in reporting rates reflected known trends in background death rates. These findings do not suggest an association between vaccination and overall increased mortality. This article is protected by copyright. All rights reserved. |
Results from the second WHO external quality assessment for the molecular detection of respiratory syncytial virus, 2019-2020.
Williams T , Jackson S , Barr I , Bi S , Bhiman J , Ellis J , von Gottberg A , Lindstrom S , Peret T , Rughooputh S , Viegas M , Hirve S , Zambon M , Zhang W , Dia N , Razanazatovo N , Al-Nabet Admh , Abubakar A , Tivane A , Barakat A , Naguib A , Aziz A , Vicari A , Moen A , Govindakarnavar A , Hall A , Darmaa B , Nathalie B , Herring B , Caetano BC , Whittaker B , Baumeister E , Nakouné E , Guthrie E , Inbanathan F , Nair H , Campbell H , Kadjo HA , Oumzil H , Heraud JM , Mott JA , Namulondo J , Leite J , Nahapetyan K , Al Ariqi L , Gazo MHI , Chadha M , Pisareva M , Venter M , Siqueira MM , Lumandas M , Niang M , Albuaini M , Salman M , Oberste S , Srikantiah P , Tang P , Couto P , Smith P , Coyle PV , Dussart P , Nguyen PN , Okada PA , Wijesinghe PR , Samuel R , Brown R , Pebody R , Fasce R , Jha R , Lindstrom S , Gerber S , Potdar V , Dong X , Deng YM . Influenza Other Respir Viruses 2023 17 (1) e13073 Background: External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable results. The Phase II, 2019–2020 World Health Organization (WHO) RSV EQA included 28 laboratories in 26 countries. The EQA panel evaluated performance in the molecular detection and subtyping of RSV-A and RSV-B. This manuscript describes the preparation, distribution, and analysis of the 2019–2020 WHO RSV EQA. Methods: Panel isolates underwent whole genome sequencing and in silico primer matching. The final panel included nine contemporary, one historical virus and two negative controls. The EQA panel was manufactured and distributed by the UK National External Quality Assessment Service (UK NEQAS). National laboratories used WHO reference assays developed by the United States Centers for Disease Control and Prevention, an RSV subtyping assay developed by the Victorian Infectious Diseases Reference Laboratory (Australia), or other in-house or commercial assays already in use at their laboratories. Results: An in silico analysis of isolates showed a good match to assay primer/probes. The panel was distributed to 28 laboratories. Isolates were correctly identified in 98% of samples for detection and 99.6% for subtyping. Conclusions: The WHO RSV EQA 2019–2020 showed that laboratories performed at high standards. Updating the composition of RSV molecular EQAs with contemporary strains to ensure representation of circulating strains, and ensuring primer matching with EQA panel viruses, is advantageous in assessing diagnostic competencies of laboratories. Ongoing EQAs are recommended because of continued evolution of mismatches between current circulating strains and existing primer sets. © 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd. |
Reports of Guillain-Barr Syndrome after COVID-19 vaccination in the United States
Abara WE , Gee J , Marquez P , Woo J , Myers TR , DeSantis A , Baumblatt JAG , Woo EJ , Thompson D , Nair N , Su JR , Shimabukuro TT , Shay DK . JAMA Netw Open 2023 6 (2) e2253845 IMPORTANCE: Because of historical associations between vaccines and Guillain-Barré syndrome (GBS), the condition was a prespecified adverse event of special interest for COVID-19 vaccine monitoring. OBJECTIVE: To evaluate GBS reports to the Vaccine Adverse Event Reporting System (VAERS) and compare reporting patterns within 21 and 42 days after vaccination with Ad26.COV2.S (Janssen), BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) COVID-19 vaccines. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted using US VAERS reports submitted during December 2020 to January 2022. GBS case reports verified as meeting the Brighton Collaboration case definition for GBS in US adults after COVID-19 vaccination were included. EXPOSURES: Receipt of the Ad26.COV2.S, BNT162b2, or mRNA-1273 COVID-19 vaccine. MAIN OUTCOMES AND MEASURES: Descriptive analyses of GBS case were conducted. GBS reporting rates within 21 and 42 days after Ad26.COV2.S, BNT162b2, or mRNA-1273 vaccination based on doses administered were calculated. Reporting rate ratios (RRRs) after receipt of Ad26.COV2.S vs BNT162b2 or mRNA-1273 within 21- and 42-day postvaccination intervals were calculated. Observed-to-expected (OE) ratios were estimated using published GBS background rates. RESULTS: Among 4 651 785 COVID-19 vaccine doses, 17 944 515 doses (3.7%) were Ad26.COV2.S, 266 859 784 doses (54.7%) were BNT162b2, and 202 847 486 doses (41.6%) were mRNA-1273. Of 295 verified reports of individuals with GBS identified after COVID-19 vaccination (12 Asian [4.1%], 18 Black [6.1%], and 193 White [65.4%]; 17 Hispanic [5.8%]; 169 males [57.3%]; median [IQR] age, 59.0 [46.0-68.0] years), 275 reports (93.2%) documented hospitalization. There were 209 and 253 reports of GBS that occurred within 21 days and 42 days of vaccination, respectively. Within 21 days of vaccination, GBS reporting rates per 1 000 000 doses were 3.29 for Ad26.COV.2, 0.29 for BNT162b2, and 0.35 for mRNA-1273 administered; within 42 days of vaccination, they were 4.07 for Ad26.COV.2, 0.34 for BNT162b2, and 0.44 for mRNA-1273. GBS was more frequently reported within 21 days after Ad26.COV2.S than after BNT162b2 (RRR = 11.40; 95% CI, 8.11-15.99) or mRNA-1273 (RRR = 9.26; 95% CI, 6.57-13.07) vaccination; similar findings were observed within 42 days after vaccination (BNT162b2: RRR = 12.06; 95% CI, 8.86-16.43; mRNA-1273: RRR = 9.27; 95% CI, 6.80-12.63). OE ratios were 3.79 (95% CI, 2.88-4.88) for 21-day and 2.34 (95% CI, 1.83-2.94) for 42-day intervals after Ad26.COV2.S vaccination and less than 1 (not significant) after BNT162b2 and mRNA-1273 vaccination within both postvaccination periods. CONCLUSIONS AND RELEVANCE: This study found disproportionate reporting and imbalances after Ad26.COV2.S vaccination, suggesting that Ad26.COV2.S vaccination was associated with increased risk for GBS. No associations between mRNA COVID-19 vaccines and risk of GBS were observed. |
Risk factors for melioidosis in Udupi district, Karnataka, India, January 2017-July 2018
Akhileshwar Singh , Ashok Talyan , Ramesh Chandra , Anubhav Srivastav , Vasudeva Upadhya , Chiranjay Mukhopadhyay , Shyamsundar Shreedhar , Deepak Sudhakaran , Suma Nair , Papanna M , Yadav R , Singh SK , Tanzin Dikid . PLoS Glob Public Health 2022 2 (12) e0000865 We initiated an epidemiological investigation following the death of a previously healthy 17 year-old boy with neuro-melioidosis. A case was defined as a culture-confirmed melioidosis patient from Udupi district admitted to hospital A from January 2013-July 2018. For the case control study, we enrolled a subset of cases admitted to hospital A from January 2017- July 2018. A control was resident of Udupi district admitted to hospital A in July 2018 with a non-infectious condition. Using a matched case-control design, we compared each case to 3 controls using age and sex groups. We assessed for risk factors related to water storage, activities of daily living, injuries and environmental exposures (three months prior to hospitalization), using conditional regression analysis. We identified 50 cases with case fatality rate 16%. Uncontrolled diabetes mellitus was present in 84% cases and 66% of cases occurred between May and October (rainy season). Percutaneous inoculation through exposure to stagnant water and injury leading to breakage in the skin were identified as an important mode of transmission. We used these findings to develop a surveillance case definition and initiated training of the district laboratory for melioidosis diagnosis. |
Needs for shelter or housing assistance among people with diagnosed HIV by jurisdiction: United States, 2015-2020
Dasgupta S , Beer L , Lu JF , Weiser J , Yuan X , Nair P , Banks L , Marcus R . AIDS 2023 37 (3) 535-540 OBJECTIVE: To describe the landscape of needs for housing assistance among people with HIV (PWH) and availability of Housing Opportunities for People with AIDS (HOPWA) funding with respect to housing service needs, nationally and for 17 US jurisdictions. DESIGN: The CDC Medical Monitoring Project (MMP) is an annual, cross-sectional survey designed to report nationally and locally representative estimates of characteristics and outcomes among adults with diagnosed HIV in the United States. METHODS: We analyzed 2015-2020 data from MMP and 2019 funding data from HOPWA. Weighted percentages and 95% confidence intervals (CIs) for national and jurisdiction-level estimates were reported. RESULTS: Nationally, 1 in 4 (27.7%) PWH had shelter or housing service needs. Among those who needed housing services, 2 in 5 (40.4%) did not receive them (range: 21.3% in New York to 62.3% in Georgia). Reasons for unmet needs were multifactorial and varied by jurisdiction. Available 2019 HOPWA funding per person in need would cover up to 1.24 months of rent per person nationally (range: 0.53 months in Virginia to 9.54 months in Puerto Rico), and may not have matched housing assistance needs among PWH in certain jurisdictions. CONCLUSION: Addressing housing service needs necessitates a multipronged approach at the provider, jurisdiction, and national level. Locally, jurisdictions should work with their partners to understand and address housing service needs among PWH. Nationally, distribution of HOPWA funding for housing services should be aligned according to local needs; the funding formula could be modified to improve access to housing services among PWH. |
Assembling a global database of child pneumonia studies to inform WHO pneumonia management algorithm: Methodology and applications
Martin H , Falconer J , Addo-Yobo E , Aneja S , Arroyo LM , Asghar R , Awasthi S , Banajeh S , Bari A , Basnet S , Bavdekar A , Bhandari N , Bhatnagar S , Bhutta ZA , Brooks A , Chadha M , Chisaka N , Chou M , Clara AW , Colbourn T , Cutland C , D'Acremont V , Echavarria M , Gentile A , Gessner B , Gregory CJ , Hazir T , Hibberd PL , Hirve S , Hooli S , Iqbal I , Jeena P , Kartasasmita CB , King C , Libster R , Lodha R , Lozano JM , Lucero M , Lufesi N , MacLeod WB , Madhi SA , Mathew JL , Maulen-Radovan I , McCollum ED , Mino G , Mwansambo C , Neuman MI , Nguyen NTV , Nunes MC , Nymadawa P , O'Grady KF , Pape JW , Paranhos-Baccala G , Patel A , Picot VS , Rakoto-Andrianarivelo M , Rasmussen Z , Rouzier V , Russomando G , Ruvinsky RO , Sadruddin S , Saha SK , Santosham M , Singhi S , Soofi S , Strand TA , Sylla M , Thamthitiwat S , Thea DM , Turner C , Vanhems P , Wadhwa N , Wang J , Zaman SM , Campbell H , Nair H , Qazi SA , Nisar YB . J Glob Health 2022 12 04075 BACKGROUND: The existing World Health Organization (WHO) pneumonia case management guidelines rely on clinical symptoms and signs for identifying, classifying, and treating pneumonia in children up to 5 years old. We aimed to collate an individual patient-level data set from large, high-quality pre-existing studies on pneumonia in children to identify a set of signs and symptoms with greater validity in the diagnosis, prognosis, and possible treatment of childhood pneumonia for the improvement of current pneumonia case management guidelines. METHODS: Using data from a published systematic review and expert knowledge, we identified studies meeting our eligibility criteria and invited investigators to share individual-level patient data. We collected data on demographic information, general medical history, and current illness episode, including history, clinical presentation, chest radiograph findings when available, treatment, and outcome. Data were gathered separately from hospital-based and community-based cases. We performed a narrative synthesis to describe the final data set. RESULTS: Forty-one separate data sets were included in the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) database, 26 of which were hospital-based and 15 were community-based. The PREPARE database includes 285839 children with pneumonia (244323 in the hospital and 41516 in the community), with detailed descriptions of clinical presentation, clinical progression, and outcome. Of 9185 pneumonia-related deaths, 6836 (74%) occurred in children <1 year of age and 1317 (14%) in children aged 1-2 years. Of the 285839 episodes, 280998 occurred in children 0-59 months old, of which 129584 (46%) were 2-11 months of age and 152730 (54%) were males. CONCLUSIONS: This data set could identify an improved specific, sensitive set of criteria for diagnosing clinical pneumonia and help identify sick children in need of referral to a higher level of care or a change of therapy. Field studies could be designed based on insights from PREPARE analyses to validate a potential revised pneumonia algorithm. The PREPARE methodology can also act as a model for disease database assembly. |
HIV stigma and health care discrimination experienced by Hispanic or Latino persons with HIV - United States, 2018-2020
Padilla M , Patel D , Beer L , Tie Y , Nair P , Salabarría-Peña Y , Henny KD , Thomas D , Dasgupta S . MMWR Morb Mortal Wkly Rep 2022 71 (41) 1293-1300 Hispanic or Latino (Hispanic) persons with HIV experience disparities in HIV health outcomes compared with some other racial and ethnic groups. A previous report found that the percentages of Hispanic persons who received HIV care, were retained in care, and were virally suppressed were lower than those among non-Hispanic White persons with HIV (1). HIV stigma and discrimination are human rights issues associated with adverse HIV outcomes; eliminating stigma and discrimination among persons with HIV is a national priority*(,)(†)(,)(§) (2,3). CDC analyzed data from the Medical Monitoring Project (MMP), an annual, cross-sectional study designed to report nationally representative estimates of experiences and outcomes among adults with diagnosed HIV. Data from the 2018-2020 cycles were analyzed to assess self-reported stigma and health care discrimination using adapted versions of validated multi-component scales among 2,690 adult Hispanic persons with HIV in the United States overall and by six characteristics.(¶) The median HIV stigma score on a scale of 0-100 was 31.7, with women (35.6) and American Indian or Alaska Native (AI/AN) persons (38.9) reporting the highest scores among Hispanic persons with HIV. HIV stigma was primarily attributed to disclosure concerns (e.g., fearing others will disclose one's HIV status and being careful about who one tells about one's HIV status). Nearly one in four (23%) Hispanic persons with HIV experienced health care discrimination. Health care discrimination was experienced more frequently by Hispanic men (23%) than by Hispanic women (18%) and by Black or African American (Black) Hispanic persons (28%) than by White Hispanic persons (21%). Understanding disparities in experiences of stigma and discrimination is important when designing culturally appropriate interventions to reduce stigma and discrimination. |
Antihypertensive and statin medication adherence among Medicare beneficiaries
Jackson SL , Nair PR , Chang A , Schieb L , Loustalot F , Wall HK , Sperling LS , Ritchey MD . Am J Prev Med 2022 63 (3) 313-323 Introduction: Medication adherence is important for optimal management of chronic conditions, including hypertension and hypercholesterolemia. This study describes adherence to antihypertensive and statin medications, individually and collectively, and examines variation in adherence by demographic and geographic characteristics. Methods: The 2017 prescription drug event data for beneficiaries with Medicare Part D coverage were assessed. Beneficiaries with a proportion of days covered 80% were considered adherent. Adjusted prevalence ratios were estimated to quantify the associations between demographic and geographic characteristics and adherence. Adherence estimates were mapped by county of residence using a spatial empirical Bayesian smoothing technique to enhance stability. Analyses were conducted in 20192021. Results: Among the 22.5 million beneficiaries prescribed antihypertensive medications, 77.1% were adherent; among the 16.1 million prescribed statin medications, 81.9% were adherent; and among the 13.5 million prescribed antihypertensive and statin medications, 70.3% were adherent to both. Adherence varied by race/ethnicity: American Indian/Alaska Native (adjusted prevalence ratio=0.83, 95% confidence limit=0.82, 0.842), Hispanic (adjusted prevalence ratio=0.90, 95% confidence limit=0.90, 0.91), and non-Hispanic Black (adjusted prevalence ratio=0.87, 95% confidence limit=0.86, 0.87) beneficiaries were less likely to be adherent than non-Hispanic White beneficiaries. County-level adherence ranged across the U.S. from 25.7% to 88.5% for antihypertensive medications, from 36.0% to 93.8% for statin medications, and from 20.8% to 92.9% for both medications combined and tended to be the lowest in the southern U.S. Conclusions: This study highlights opportunities for efforts to remove barriers and support medication adherence, especially among racial/ethnic minority groups and within the regions at greatest risk for adverse cardiovascular outcomes. 2022 |
Industry-specific prevalence of elevated blood lead levels among Pennsylvania workers, 2007-2018
Tsai RJ , Lu JW , Henn SA , Hasanali SH , Harduar-Morano L , Nair A . Occup Environ Med 2022 OBJECTIVES: To use industry-specific denominators to more accurately examine trends in prevalence rates for occupational cases of elevated blood lead levels (eBLLs) in Pennsylvania. METHODS: We used adult (aged ≥16 years) blood lead level data from Pennsylvania (2007-2018) and industry-specific denominator data from the US Census Bureau's County Business Patterns to calculate prevalence rates for eBLLs, defined as ≥25 µg/dL. RESULTS: Of the 19 904 cases with eBLLs, 92% were due to occupational lead exposure, with 83% from workers in the battery manufacturing industry. In 2018, the prevalence rate of eBLLs for battery manufacturing (8036.4 cases per 100 000 employed battery manufacturing workers) was 543 times the overall Pennsylvania prevalence rate. The prevalence rate for battery manufacturing steeply declined 71% from 2007 to 2018. CONCLUSIONS: The battery manufacturing industry had the highest burden of occupational lead exposure in Pennsylvania, illustrating the importance of using industry-specific denominators to accurately identify sources of lead exposure. Although the prevalence rate of eBLLs declined over time, lead exposure remains a major concern among battery manufacturing workers. |
Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis
Li Y , Wang X , Blau DM , Caballero MT , Feikin DR , Gill CJ , Madhi SA , Omer SB , Simões EAF , Campbell H , Pariente AB , Bardach D , Bassat Q , Casalegno JS , Chakhunashvili G , Crawford N , Danilenko D , Do LAH , Echavarria M , Gentile A , Gordon A , Heikkinen T , Huang QS , Jullien S , Krishnan A , Lopez EL , Markić J , Mira-Iglesias A , Moore HC , Moyes J , Mwananyanda L , Nokes DJ , Noordeen F , Obodai E , Palani N , Romero C , Salimi V , Satav A , Seo E , Shchomak Z , Singleton R , Stolyarov K , Stoszek SK , von Gottberg A , Wurzel D , Yoshida LM , Yung CF , Zar HJ , Nair H . Lancet 2022 399 (10340) 2047-2064 BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. METHODS: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). FINDINGS: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). INTERPRETATION: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU). |
Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries
Rees CA , Colbourn T , Hooli S , King C , Lufesi N , McCollum ED , Mwansambo C , Cutland C , Madhi SA , Nunes M , Matthew JL , Addo-Yobo E , Chisaka N , Hassan M , Hibberd PL , Jeena PM , Lozano JM , MacLeod WB , Patel A , Thea DM , Nguyen NTV , Kartasasmita CB , Lucero M , Awasthi S , Bavdekar A , Chou M , Nymadawa P , Pape JW , Paranhos-Baccala G , Picot VS , Rakoto-Andrianarivelo M , Rouzier V , Russomando G , Sylla M , Vanhems P , Wang J , Asghar R , Banajeh S , Iqbal I , Maulen-Radovan I , Mino-Leon G , Saha SK , Santosham M , Singhi S , Basnet S , Strand TA , Bhatnagar S , Wadhwa N , Lodha R , Aneja S , Clara AW , Campbell H , Nair H , Falconer J , Qazi SA , Nisar YB , Neuman MI . BMJ Glob Health 2022 7 (4) INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings. METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool. RESULTS: A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84). CONCLUSIONS: The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality. |
Defining the risk of SARS-CoV-2 variants on immune protection.
DeGrace MM , Ghedin E , Frieman MB , Krammer F , Grifoni A , Alisoltani A , Alter G , Amara RR , Baric RS , Barouch DH , Bloom JD , Bloyet LM , Bonenfant G , Boon ACM , Boritz EA , Bratt DL , Bricker TL , Brown L , Buchser WJ , Carreo JM , Cohen-Lavi L , Darling TL , Davis-Gardner ME , Dearlove BL , Di H , Dittmann M , Doria-Rose NA , Douek DC , Drosten C , Edara VV , Ellebedy A , Fabrizio TP , Ferrari G , Florence WC , Fouchier RAM , Franks J , Garca-Sastre A , Godzik A , Gonzalez-Reiche AS , Gordon A , Haagmans BL , Halfmann PJ , Ho DD , Holbrook MR , Huang Y , James SL , Jaroszewski L , Jeevan T , Johnson RM , Jones TC , Joshi A , Kawaoka Y , Kercher L , Koopmans MPG , Korber B , Koren E , Koup RA , LeGresley EB , Lemieux JE , Liebeskind MJ , Liu Z , Livingston B , Logue JP , Luo Y , McDermott AB , McElrath MJ , Meliopoulos VA , Menachery VD , Montefiori DC , Mhlemann B , Munster VJ , Munt JE , Nair MS , Netzl A , Niewiadomska AM , O'Dell S , Pekosz A , Perlman S , Pontelli MC , Rockx B , Rolland M , Rothlauf PW , Sacharen S , Scheuermann RH , Schmidt SD , Schotsaert M , Schultz-Cherry S , Seder RA , Sedova M , Sette A , Shabman RS , Shen X , Shi PY , Shukla M , Simon V , Stumpf S , Sullivan NJ , Thackray LB , Theiler J , Thomas PG , Trifkovic S , Treli S , Turner SA , Vakaki MA , vanBakel H , VanBlargan LA , Vincent LR , Wallace ZS , Wang L , Wang M , Wang P , Wang W , Weaver SC , Webby RJ , Weiss CD , Wentworth DE , Weston SM , Whelan SPJ , Whitener BM , Wilks SH , Xie X , Ying B , Yoon H , Zhou B , Hertz T , Smith DJ , Diamond MS , Post DJ , Suthar MS . Nature 2022 605 (7911) 640-652 The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced following infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases (NIAID) within the National Institutes of Health (NIH) established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants potentially impacting transmission, virulence, and resistance to convalescent and vaccine-induced immunity. The SAVE program serves as a critical data-generating component of the United States Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines, and therapeutics and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity, and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models, and pivotal findings facilitated by this collaborative approach and identify future challenges. This program serves as a template for the response against rapidly evolving pandemic pathogens by monitoring viral evolution in the human population to identify variants that could erode the effectiveness of countermeasures. |
Transmission of SARS-CoV-2 from humans to a 16-year-old domestic cat with comorbidities in Pennsylvania, USA.
Tewari D , Boger L , Brady S , Livengood J , Killian ML , Nair MS , Thirumalapura N , Kuchipudi SV , Zellers C , Schroder B , Torchetti M , Carpenter A , Kunkel A , Brightbill K . Vet Med Sci 2021 8 (2) 899-906 BACKGROUND AND OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), besides causing human infection, has been shown to naturally infect several susceptible animal species including large cats (tigers, lions, pumas, spotted leopards), dogs, cats, ferrets, gorillas and minks. Cats and minks are continuing to be the most reported species with SARS-CoV-2 infections among animals but it needs to be investigated further. METHODS AND RESULTS: We report the detection of SARS-CoV-2 from a domestic cat that exhibited respiratory disease after being exposed to SARS-CoV-2 virus from humans in the same household. SARS-CoV-2 RNA was detected in two oropharyngeal swabs collected at two time points, 11 days apart; the first, when the cat was reported to be sick and the second, before euthanasia due to poor prognosis. The viral nucleic acid detected at two time points showed no genomic variation and resembled the clade GH circulating in humans in the United States. Clinical and pathological findings noted in this 16-year-old cat were consistent with respiratory and cardiac insufficiency. CONCLUSIONS: SARS-CoV-2 viral infection was likely an incidental clinical finding, as the virus was not detected in fixed lungs, heart, or kidney tissues. Only fresh lung tissue collected at necropsy showed the presence of viral nucleic acid, albeit at a very low level. Further research is needed to clarify the clinical course of SARS-CoV-2 in companion animals of advanced age and underlying cardiac disease. |
Strategies and Patterns of Codon Bias in Molluscum Contagiosum Virus.
Nair RR , Mohan M , Rudramurthy GR , Vivekanandam R , Satheshkumar PS . Pathogens 2021 10 (12) Trends associated with codon usage in molluscum contagiosum virus (MCV) and factors governing the evolution of codon usage have not been investigated so far. In this study, attempts were made to decipher the codon usage trends and discover the major evolutionary forces that influence the patterns of codon usage in MCV with special reference to sub-types 1 and 2, MCV-1 and MCV-2, respectively. Three hypotheses were tested: (1) codon usage patterns of MCV-1 and MCV-2 are identical; (2) SCUB (synonymous codon usage bias) patterns of MCV-1 and MCV-2 slightly deviate from that of human host to avoid affecting the fitness of host; and (3) translational selection predominantly shapes the SCUB of MCV-1 and MCV-2. Various codon usage indices viz. relative codon usage value, effective number of codons and codon adaptation index were calculated to infer the nature of codon usage. Correspondence analysis and correlation analysis were performed to assess the relative contribution of silent base contents and significance of codon usage indices in defining bias in codon usage. Among the tested hypotheses, only the second and third hypotheses were accepted. |
Fatal Multisystem Inflammatory Syndrome in Adult after SARS-CoV-2 Natural Infection and COVID-19 Vaccination.
Grome HN , Threlkeld M , Threlkeld S , Newman C , Martines RB , Reagan-Steiner S , Whitt MA , Gomes-Solecki M , Nair N , Fill MM , Jones TF , Schaffner W , Dunn J . Emerg Infect Dis 2021 27 (11) 2914-2918 We describe a fatal case of multisystem inflammatory syndrome in an adult with onset 22 days after a second dose of mRNA coronavirus disease vaccine. Serologic and clinical findings indicated severe acute respiratory syndrome coronavirus 2 infection occurred before vaccination. The immunopathology of this syndrome, regardless of vaccination status, remains poorly understood. |
Use of COVID-19 Vaccines After Reports of Adverse Events Among Adult Recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 Vaccines (Pfizer-BioNTech and Moderna): Update from the Advisory Committee on Immunization Practices - United States, July 2021.
Rosenblum HG , Hadler SC , Moulia D , Shimabukuro TT , Su JR , Tepper NK , Ess KC , Woo EJ , Mba-Jonas A , Alimchandani M , Nair N , Klein NP , Hanson KE , Markowitz LE , Wharton M , McNally VV , Romero JR , Talbot HK , Lee GM , Daley MF , Mbaeyi SA , Oliver SE . MMWR Morb Mortal Wkly Rep 2021 70 (32) 1094-1099 In December 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for Pfizer-BioNTech and Moderna COVID-19 vaccines, and in February 2021, FDA issued an EUA for the Janssen (Johnson & Johnson) COVID-19 vaccine. After each EUA, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for vaccine use; currently Pfizer-BioNTech is authorized and recommended for persons aged ≥12 years and Moderna and Janssen for persons aged ≥18 years (1-3). Both Pfizer-BioNTech and Moderna vaccines, administered as 2-dose series, are mRNA-based COVID-19 vaccines, whereas the Janssen COVID-19 vaccine, administered as a single dose, is a recombinant replication-incompetent adenovirus-vector vaccine. As of July 22, 2021, 187 million persons in the United States had received at least 1 dose of COVID-19 vaccine (4); close monitoring of safety surveillance has demonstrated that serious adverse events after COVID-19 vaccination are rare (5,6). Three medical conditions have been reported in temporal association with receipt of COVID-19 vaccines. Two of these (thrombosis with thrombocytopenia syndrome [TTS], a rare syndrome characterized by venous or arterial thrombosis and thrombocytopenia, and Guillain-Barré syndrome [GBS], a rare autoimmune neurologic disorder characterized by ascending weakness and paralysis) have been reported after Janssen COVID-19 vaccination. One (myocarditis, cardiac inflammation) has been reported after Pfizer-BioNTech COVID-19 vaccination or Moderna COVID-19 vaccination, particularly after the second dose; these were reviewed together and will hereafter be referred to as mRNA COVID-19 vaccination. ACIP has met three times to review the data associated with these reports of serious adverse events and has comprehensively assessed the benefits and risks associated with receipt of these vaccines. During the most recent meeting in July 2021, ACIP determined that, overall, the benefits of COVID-19 vaccination in preventing COVID-19 morbidity and mortality outweigh the risks for these rare serious adverse events in adults aged ≥18 years; this balance of benefits and risks varied by age and sex. ACIP continues to recommend COVID-19 vaccination in all persons aged ≥12 years. CDC and FDA continue to closely monitor reports of serious adverse events and will present any additional data to ACIP for consideration. Information regarding risks and how they vary by age and sex and type of vaccine should be disseminated to providers, vaccine recipients, and the public. |
Global burden of acute lower respiratory infection associated with human parainfluenza virus in children younger than 5 years for 2018: a systematic review and meta-analysis
Wang X , Li Y , Deloria-Knoll M , Madhi SA , Cohen C , Arguelles VL , Basnet S , Bassat Q , Brooks WA , Echavarria M , Fasce RA , Gentile A , Goswami D , Homaira N , Howie SRC , Kotloff KL , Khuri-Bulos N , Krishnan A , Lucero MG , Lupisan S , Mathisen M , McLean KA , Mira-Iglesias A , Moraleda C , Okamoto M , Oshitani H , O'Brien KL , Owor BE , Rasmussen ZA , Rath BA , Salimi V , Sawatwong P , Scott JAG , Simões EAF , Sotomayor V , Thea DM , Treurnicht FK , Yoshida LM , Zar HJ , Campbell H , Nair H . Lancet Glob Health 2021 9 (8) e1077-e1087 BACKGROUND: Human parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global burden of hPIV in childhood ALRI. We aimed to estimate the global and regional hPIV-associated and hPIV-attributable ALRI incidence, hospital admissions, and mortality for children younger than 5 years and stratified by 0-5 months, 6-11 months, and 12-59 months of age. METHODS: We did a systematic review of hPIV-associated ALRI burden studies published between Jan 1, 1995, and Dec 31, 2020, found in MEDLINE, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Global Health Library, three Chinese databases, and Google search, and also identified a further 41 high-quality unpublished studies through an international research network. We included studies reporting community incidence of ALRI with laboratory-confirmed hPIV; hospital admission rates of ALRI or ALRI with hypoxaemia in children with laboratory-confirmed hPIV; proportions of patients with ALRI admitted to hospital with laboratory-confirmed hPIV; or in-hospital case-fatality ratios (hCFRs) of ALRI with laboratory-confirmed hPIV. We used a modified Newcastle-Ottawa Scale to assess risk of bias. We analysed incidence, hospital admission rates, and hCFRs of hPIV-associated ALRI using a generalised linear mixed model. Adjustment was made to account for the non-detection of hPIV-4. We estimated hPIV-associated ALRI cases, hospital admissions, and in-hospital deaths using adjusted incidence, hospital admission rates, and hCFRs. We estimated the overall hPIV-associated ALRI mortality (both in-hospital and out-hospital mortality) on the basis of the number of in-hospital deaths and care-seeking for child pneumonia. We estimated hPIV-attributable ALRI burden by accounting for attributable fractions for hPIV in laboratory-confirmed hPIV cases and deaths. Sensitivity analyses were done to validate the estimates of overall hPIV-associated ALRI mortality and hPIV-attributable ALRI mortality. The systematic review protocol was registered on PROSPERO (CRD42019148570). FINDINGS: 203 studies were identified, including 162 hPIV-associated ALRI burden studies and a further 41 high-quality unpublished studies. Globally in 2018, an estimated 18·8 million (uncertainty range 12·8-28·9) ALRI cases, 725 000 (433 000-1 260 000) ALRI hospital admissions, and 34 400 (16 400-73 800) ALRI deaths were attributable to hPIVs among children younger than 5 years. The age-stratified and region-stratified analyses suggested that about 61% (35% for infants aged 0-5 months and 26% for 6-11 months) of the hospital admissions and 66% (42% for infants aged 0-5 months and 24% for 6-11 months) of the in-hospital deaths were in infants, and 70% of the in-hospital deaths were in low-income and lower-middle-income countries. Between 73% and 100% (varying by outcome) of the data had a low risk in study design; the proportion was 46-65% for the adjustment for health-care use, 59-77% for patient groups excluded, 54-93% for case definition, 42-93% for sampling strategy, and 67-77% for test methods. Heterogeneity in estimates was found between studies for each outcome. INTERPRETATION: We report the first global burden estimates of hPIV-associated and hPIV-attributable ALRI in young children. Globally, approximately 13% of ALRI cases, 4-14% of ALRI hospital admissions, and 4% of childhood ALRI mortality were attributable to hPIV. These numbers indicate a potentially notable burden of hPIV in ALRI morbidity and mortality in young children. These estimates should encourage and inform investment to accelerate the development of targeted interventions. FUNDING: Bill & Melinda Gates Foundation. |
US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021.
See I , Su JR , Lale A , Woo EJ , Guh AY , Shimabukuro TT , Streiff MB , Rao AK , Wheeler AP , Beavers SF , Durbin AP , Edwards K , Miller E , Harrington TA , Mba-Jonas A , Nair N , Nguyen DT , Talaat KR , Urrutia VC , Walker SC , Creech CB , Clark TA , DeStefano F , Broder KR . JAMA 2021 325 (24) 2448-2456 IMPORTANCE: Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021. OBJECTIVE: To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt. DESIGN, SETTING, AND PARTICIPANTS: Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021). EXPOSURES: Receipt of Ad26.COV2.S vaccine. MAIN OUTCOMES AND MEASURES: Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians. RESULTS: Patients' ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 ×103/µL to 127 ×103/µL. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4). CONCLUSIONS AND RELEVANCE: The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia. |
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