Publications by authors named "Eric A F Simões"

142 Publications

Adult population coverage with influenza vaccine and influenza hospitalization rates-is there a role for active outreach to immunize at-risk neighborhoods?

Clin Infect Dis 2021 Mar 14. Epub 2021 Mar 14.

Colorado School of Public Health, Aurora, Colorado, USA.

We evaluated whether Denver neighborhoods with elevated rates of adult laboratory-confirmed influenza hospitalization had lower adult coverage with influenza vaccine. Overall vaccine coverage was low. Hospitalization rates were associated with demographic and socioeconomic characteristics. Active immunization of at-risk neighborhoods may be necessary to address disparities in influenza hospitalization rates.
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http://dx.doi.org/10.1093/cid/ciab231DOI Listing
March 2021

Risk Factors for Respiratory Syncytial Virus Lower Respiratory Tract Infections: Evidence from an Indonesian Cohort.

Viruses 2021 02 21;13(2). Epub 2021 Feb 21.

Department of Infectious Disease, University of Colorado School of Medicine & Children's Hospital Colorado, Aurora, CO 80045, USA.

Although risk factors for hospitalization from a respiratory syncytial virus (RSV) are well known, RSV lower respiratory tract infections (LRIs) in the community are much less studied or understood, especially in developing countries. In a prospective, cohort study we studied factors predisposing Indonesian infants and children under 5 years of age to developing RSV LRIs. Subjects were enrolled in two cohorts: a birth cohort and a cross-sectional cohort of children <48 months of age. Subjects were visited weekly at home to identify any LRI, using the World Health Organization's criteria. RSV etiology was determined through analysis of nasal washings by enzyme immunoassay and polymerase chain reaction. Risk factors for the development of the first documented RSV LRI were identified by multivariate analysis using logistic regression and Cox proportional hazard modeling. Of the 2014 children studied, 999 were enrolled within 30 days of birth. There were 149 first episodes of an RSV. Risk factors for an RSV LRI were poverty ( < 0.01), use of kerosene as a cooking fuel ( < 0.05), and household ownership of rabbits and chickens ( < 0.01). Our findings suggested that in a middle-income country such as Indonesia, with a substantial burden of RSV morbidity and mortality, lower socioeconomic status, environmental air quality, and animal exposure are predisposing factors for developing an RSV LRI.
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http://dx.doi.org/10.3390/v13020331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924644PMC
February 2021

Population-based otoscopic and audiometric assessment of a birth cohort recruited for a pneumococcal vaccine trial 15-18 years earlier: a protocol.

BMJ Open 2021 Feb 17;11(2):e042363. Epub 2021 Feb 17.

Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado, USA.

Introduction: A cohort of 12 000 children in the Philippines who had enrolled in a 2000-2004 (current ages 16 to 20 years) Phase 3 11-valent pneumococcal conjugate vaccine for the prevention of radiographically confirmed pneumonia are now being asked to participate in a separate study (expected completion date September 2021) to assess the cohort's current long-term audiometric and otologic status. This new study would allow assessments of the utility of the pneumococcal vaccine in conferring its protective effects on the long-term sequelae of otitis media (OM), if any. Lack of trained local healthcare providers in otolaryngology/audiology and testing equipment in Bohol, Philippines, necessitates the development of a distinct methodology that would lead to meaningful data analysis.

Methods And Analysis: Reliable data collection and transfer are achieved by a US otolaryngologist/audiologist team training local nurses on all procedures in a didactic and hands-on process. An assortment of portable otolaryngologic and audiologic equipment suitable for field testing has been acquired, including an operating otoscope (Welch-Allyn), a video-otoscope (JedMed), a tympanometer with distortion product otoacoustic emission measurements (Path Sentiero) and a screening audiometer (HearScreen). Data will then be uploaded to a Research Electronic Data Capture database in the USA.Tympanometric and audiologic data will be codified through separate conventional algorithms. A team of paediatric otolaryngology advanced practice providers (APPs) have been trained and validated in interpreting video otoscopy. The protocol for classification of diagnostic outcome variables based on video otoscopy and tympanometry has been developed and is being used by APPs to evaluate all otoscopy data.

Ethics And Dissemination: The study was approved by the Research Institute of Tropical Medicine, Alabang, Manila, Philippines, and the institutional review board and the Colorado Multiple Institutional Review Board of the University of Colorado School of Medicine, Aurora, Colorado, USA.Research results will be made available to children and their caregivers with abnormal audiologic outcomes, the funders and other researchers.

Trial Registration Number: ISRCTN 62323832; Post-results.
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http://dx.doi.org/10.1136/bmjopen-2020-042363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893663PMC
February 2021

Reopening Schools and the Dynamics of SARS-CoV-2 Infections in Israel: A Nationwide Study.

Clin Infect Dis 2021 Jan 18. Epub 2021 Jan 18.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: The benefits of school reopening must be weighed against the morbidity and mortality risks and the impact of enhancing spread of COVID-19. We investigated the effects of school reopening and easing of social distancing restrictions on the dynamics of SARS-CoV-2 infections in Israel, between March-July 2020.

Methods: We examined the nationwide agewise weekly incidence, prevalence, SARS-CoV-2 PCR tests, their positivity, COVID-19 hospitalizations and associated mortality. Temporal differences in these parameters following school reopening, school ending, and following easing of restrictions such as permission of large scale gatherings, were examined.

Results: The incidence of SARS-CoV-2 infections gradually increased following school reopening in all age groups, with a significantly higher increase in adults compared to children. Higher relative ratios (RRs) of sample positivity rates 21-27 days following school reopening relative to positivity rates prior to openings were found for the age groups 40-59 (RR: 4.72, 95% CI: 3.26 - 6.83) and 20-39 years (RR: 3.37 [2.51 - 4.53]), but not for children aged 0-9 (RR: 1.46 [0.85 - 2.51]) and 10-19 years (RR: 0.93 [0.65 - 1.34]).No increase was observed in COVID-19 associated hospitalizations and deaths following school reopening. In contrast, permission of large-scale gatherings was accompanied by increases in incidence and positivity rates of samples for all age groups, and increased hospitalizations and mortality.

Conclusions: This analysis does not support a major role of school reopening in the resurgence of the COVID-19 curve in Israel. Easing restrictions on large scale gatherings was the major influence on this resurgence.
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http://dx.doi.org/10.1093/cid/ciab035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929073PMC
January 2021

Respiratory Syncytial Virus-Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis.

J Infect Dis 2020 Dec 21. Epub 2020 Dec 21.

Pfizer Vaccines, Collegeville, PA.

Background: Although global reviews of infant RSV burden exist, none have summarized data from the United States or evaluated how RSV burden estimates are influenced by variations in study design.

Methods: We performed a systematic literature review and meta-analysis of studies describing RSV-associated hospitalization rates among US infants and examined the impact of key study characteristics on these estimates.

Results: We reviewed 3328 articles through August 14, 2020 and identified 25 studies with 31 unique estimates of RSV-associated hospitalization rates. Among US infants <1 year of age, annual rates ranged from 8.4 to 40.8 per 1000 with a pooled rate= 19.4 (95%CI: 17.9-20.9). Study type influenced RSV-associated hospitalization rates (P=.003), with active surveillance studies having pooled rates (11.0; 95%CI: 9.8-12.2) that were half that of studies based on administrative claims (21.4; 95%CI: 19.5-23.3) or modeling approaches (23.2; 95%CI: 20.2-26.2).

Conclusions: Applying our pooled rates to the 2020 US birth cohort suggests that 79,850 (95%CI: 73,680-86,020) RSV-associated infant hospitalizations occur each year. The full range of RSV-associated hospitalization rates identified in our review can better inform future evaluations of RSV prevention strategies. More research is needed to better understand differences in estimated RSV burden across study design.
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http://dx.doi.org/10.1093/infdis/jiaa752DOI Listing
December 2020

Single-dose nirsevimab prevents RSV infection.

J Pediatr 2021 01;228:310-313

University of Colorado School of Medicine and Center for Global Health, Aurora, Colorado.

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http://dx.doi.org/10.1016/j.jpeds.2020.10.066DOI Listing
January 2021

Global burden of acute lower respiratory infection associated with human metapneumovirus in children under 5 years in 2018: a systematic review and modelling study.

Lancet Glob Health 2021 01 26;9(1):e33-e43. Epub 2020 Nov 26.

Centre for Global Health, Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, UK. Electronic address:

Background: Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years.

Methods: We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus-associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths.

Findings: In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries.

Interpretation: Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries.

Funding: Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S2214-109X(20)30393-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783516PMC
January 2021

Temporal airway microbiome changes related to ventilator-associated pneumonia in children.

Eur Respir J 2021 Mar 18;57(3). Epub 2021 Mar 18.

Biostatistics and Informatics, University of Colorado, Colorado School of Public Health, Aurora, CO, USA.

We sought to determine whether temporal changes in the lower airway microbiome are associated with ventilator-associated pneumonia (VAP) in children.Using a multicentre prospective study of children aged 31 days to 18 years requiring mechanical ventilation support for >72 h, daily tracheal aspirates were collected and analysed by sequencing of the 16S rRNA gene. VAP was assessed using 2008 Centers for Disease Control and Prevention paediatric criteria. The association between microbial factors and VAP was evaluated using joint longitudinal time-to-event modelling, matched case-control comparisons and unsupervised clustering.Out of 366 eligible subjects, 66 (15%) developed VAP at a median of 5 (interquartile range 3-5) days post intubation. At intubation, there was no difference in total bacterial load (TBL), but Shannon diversity and the relative abundance of , Lactobacillales and were lower for VAP subjects non-VAP subjects. However, higher TBL on each sequential day was associated with a lower hazard (hazard ratio 0.39, 95% CI 0.23-0.64) for developing VAP, but sequential values of diversity were not associated with VAP. Similar findings were observed from the matched analysis and unsupervised clustering. The most common dominant VAP pathogens included species (19%), (14%) and / (10%). and were also identified as dominant organisms in several subjects.In mechanically ventilated children, changes over time in microbial factors were marginally associated with VAP risk, although these changes were not suitable for predicting VAP in individual patients. These findings suggest that focusing exclusively on pathogen burden may not adequately inform VAP diagnosis.
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http://dx.doi.org/10.1183/13993003.01829-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979474PMC
March 2021

Suptavumab for the Prevention of Medically Attended Respiratory Syncytial Virus Infection in Preterm Infants.

Clin Infect Dis 2020 Sep 8. Epub 2020 Sep 8.

Regeneron Pharmaceuticals, Inc, Tarrytown, New York, USA.

Background: Respiratory syncytial virus (RSV) is a major cause of childhood medically attended respiratory infection (MARI).

Methods: We conducted a randomized, double-blind, placebo-controlled phase 3 trial in 1154 preterm infants of 1 or 2 doses of suptavumab, a human monoclonal antibody that can bind and block a conserved epitope on RSV A and B subtypes, for the prevention of RSV MARI. The primary endpoint was proportion of subjects with RSV-confirmed hospitalizations or outpatient lower respiratory tract infection (LRTI).

Results: There were no significant differences between primary endpoint rates (8.1%, placebo; 7.7%, 1-dose; 9.3%, 2-dose). Suptavumab prevented RSV A infections (relative risks, .38; 95% confidence interval [CI], .14-1.05 in the 1-dose group and .39 [95% CI, .14-1.07] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P = .0499), while increasing the rate of RSV B infections (relative risk 1.36 [95% CI, .73-2.56] in the 1-dose group and 1.69 [95% CI, .92-3.08] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P = .12). Sequenced RSV isolates demonstrated no suptavumab epitope changes in RSV A isolates, while all RSV B isolates had 2-amino acid substitution in the suptavumab epitope that led to loss of neutralization activity. Treatment emergent adverse events were balanced across treatment groups.

Conclusions: Suptavumab did not reduce overall RSV hospitalizations or outpatient LRTI because of a newly circulating mutant strain of RSV B. Genetic variation in circulating RSV strains will continue to challenge prevention efforts.

Clinical Trials Registration: NCT02325791. https://clinicaltrials.gov/ct2/show/NCT02325791.
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http://dx.doi.org/10.1093/cid/ciaa951DOI Listing
September 2020

Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants.

N Engl J Med 2020 07;383(5):426-439

From the Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, and the Department of Science and Technology-National Research Foundation, Vaccine Preventable Diseases, University of the Witwatersrand (S.A.M., C.L.C.), and Shandukani Research Centre, Wits Reproductive Health and HIV Institute (M.S.M.), Johannesburg, Setshaba Research Centre, Soshanguve (K.A., A.O.), and the Family Centre for Research with Ubuntu, Department of Paediatrics and Child Health, Stellenbosch University, Tygerberg Hospital (M.F.C.), and the Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, South African Medical Research Council Unit on Child and Adolescent Health, University of Cape Town (H.J.Z.), Cape Town - all in South Africa; Fundación INFANT (F.P.P., R.L.), Hospital Militar Central Dr. Cosme Argerich (G.P.M.), and the National Scientific and Technical Research Council (R.L.), Buenos Aires, and the Department of Pediatric Pulmonology, Hospital del Niño Jesús, Tucumán (C.J.L.) - both in Argentina; the Departments of Pediatrics and Molecular Virology and Microbiology, Baylor College of Medicine, Houston (P.A.P., F.M.M.); the University of Auckland, Middlemore Hospital, Auckland, New Zealand (A.A.T.); the Department of Pediatrics, University of Colorado School of Medicine, and the Children's Hospital Colorado, Center for Global Health, Colorado School of Public Health, Aurora (E.A.F.S.); the Department of Obstetrics and Gynecology, Duke University, Durham, NC (G.K.S.); Novavax (S.A., A.A., J.C., I.C., A.F., J.S.P., V.S., D.N.T., J.W., G.M.G., L.F.F.), Gaithersburg, and the Department of International Health, International Center for Maternal and Newborn Health (A.H.B.), and the Center for American Indian Health, Department of International Health (L.H.), Johns Hopkins Bloomberg School of Public Health, Baltimore - all in Maryland; the Vaccine Institute (A.C., P.T.H.) and the Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute (A.K.), St. George's, University of London, London, Paediatric Infectious Diseases, Clinical and Experimental Sciences, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton (C.E.J.), and the Oxford Vaccine Group, Department of Paediatrics, University of Oxford and National Institute for Health Research Oxford Biomedical Research Centre (M.D.S.), and the Nuffield Department of Women's and Reproductive Health, University of Oxford (M.V.), Oxford - all in the United Kingdom; the Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle (J.A.E.);the Department of Obstetrics and Gynecology, Wayne State University, Detroit (B.G.); the Research Institute for Tropical Medicine, Muntinlupa, Philippines (J.N.J., M.L.); the Department of Pediatrics (D.W.K.) and the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology and Center for Women's Reproductive Health (A.T.T.), University of Alabama, Birmingham; the Women's and Children's Hospital and Robinson Research Institute, University of Adelaide, Adelaide, SA (H.S.M.), the Melbourne School of Population and Global Health, University of Melbourne, and Murdoch Children's Research Institute, Parkville, VIC (T.M.N., K.P.P.), and Wesfarmers Center of Vaccines and Infectious Diseases, Telethon Kids Institute, Division of Paediatrics, School of Medicine, University of Western Australia, Perth Children's Hospital, Perth (P.C.R., T.S.) - all in Australia; Marshfield Clinic Research Institute, Marshfield, WI (J.K.M.); Pediatría Clínica, Infectología y Traslacional Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain (F.M.-T.); the Division of General Pediatrics, Department of Pediatrics, School of Medicine (J.H.S.), and the Department of Obstetrics and Gynecology (M.W.V.), University of Utah Health Sciences Center, Salt Lake City; Meridian Clinical Research, Norfolk, NE (K.V.); and the International Center for Diarrhoeal Disease Research Bangladesh, Dhaka (K.Z.).

Background: Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants.

Methods: Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%).

Results: A total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, -1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, -8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups.

Conclusions: RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.).
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http://dx.doi.org/10.1056/NEJMoa1908380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299433PMC
July 2020

Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants.

N Engl J Med 2020 07;383(5):415-425

From AstraZeneca, Gaithersburg, MD (M.P.G., Y.Y., T.T., M.T.E., A.A.K., F.D., T.V.); SUNY Upstate Medical University, Syracuse, NY (J.B.D.); Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, and Department of Science and Technology/National Research Foundation South African Research Chair, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg (S.A.M.); the Division of Pediatrics and Neonatology, Department of Maternal, Neonatal, and Infant Medicine, Nuovo Ospedale Degli Infermi, Biella, and Neonatology and NICU, Sant'Anna Hospital, AOU Città della Salute e della Scienza, Turin - both in Italy (P.M.); the University of Colorado School of Medicine, Aurora (E.A.F.S.); and the Children's Foundation Research Institute at Le Bonheur Children's Hospital, Memphis, TN (J.P.D.V.).

Background: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants, and a need exists for prevention of RSV in healthy infants. Nirsevimab is a monoclonal antibody with an extended half-life that is being developed to protect infants for an entire RSV season with a single intramuscular dose.

Methods: In this trial conducted in both northern and southern hemispheres, we evaluated nirsevimab for the prevention of RSV-associated lower respiratory tract infection in healthy infants who had been born preterm (29 weeks 0 days to 34 weeks 6 days of gestation). We randomly assigned the infants in a 2:1 ratio to receive nirsevimab, at a dose of 50 mg in a single intramuscular injection, or placebo at the start of an RSV season. The primary end point was medically attended RSV-associated lower respiratory tract infection through 150 days after administration of the dose. The secondary efficacy end point was hospitalization for RSV-associated lower respiratory tract infection through 150 days after administration of the dose.

Results: From November 2016 through November 2017, a total of 1453 infants were randomly assigned to receive nirsevimab (969 infants) or placebo (484 infants) at the start of the RSV season. The incidence of medically attended RSV-associated lower respiratory tract infection was 70.1% lower (95% confidence interval [CI], 52.3 to 81.2) with nirsevimab prophylaxis than with placebo (2.6% [25 infants] vs. 9.5% [46 infants]; P<0.001) and the incidence of hospitalization for RSV-associated lower respiratory tract infection was 78.4% lower (95% CI, 51.9 to 90.3) with nirsevimab than with placebo (0.8% [8 infants] vs. 4.1% [20 infants]; P<0.001). These differences were consistent throughout the 150-day period after the dose was administered and across geographic locations and RSV subtypes. Adverse events were similar in the two trial groups, with no notable hypersensitivity reactions.

Conclusions: A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout the RSV season in healthy preterm infants. (Funded by AstraZeneca and Sanofi Pasteur; ClinicalTrials.gov number, NCT02878330.).
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http://dx.doi.org/10.1056/NEJMoa1913556DOI Listing
July 2020

Evaluation of rates of laboratory-confirmed influenza hospitalization in rural and urban census tracts over eight influenza seasons.

Prev Med 2020 10 29;139:106184. Epub 2020 Jun 29.

Colorado School of Public Health, Aurora, CO 80045, USA; University of Colorado School of Medicine, 13001 E. 17th Pl., Aurora, CO 80045, USA.

The burden of influenza in rural areas is largely unstudied. Rural populations may be vulnerable yet isolated from circulating virus. Laboratory-confirmed influenza hospitalizations in rural Colorado census tracts over eight influenza seasons were inconsistently distributed across seasons. Rural rates were, on average, lower than urban rates. Race, ethnicity, poverty, health insurance coverage, and distance from a hospital accounted for rate differences. Our interpretation is: 1) influenza regularly circulates in urban areas and inconsistently spreads to rural areas, 2) demographic and socioeconomic factors drive morbidity in exposed populations, and 3) public health interventions targeting high-risk urban census tracts may be beneficial.
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http://dx.doi.org/10.1016/j.ypmed.2020.106184DOI Listing
October 2020

Efficacy, duration of protection, birth outcomes, and infant growth associated with influenza vaccination in pregnancy: a pooled analysis of three randomised controlled trials.

Lancet Respir Med 2020 06;8(6):597-608

Bill & Melinda Gates Foundation, Seattle, WA, USA; Vaccines For All, Pune, India.

Background: Maternal influenza immunisation can reduce morbidity and mortality associated with influenza infection in pregnant women and young infants. We aimed to determine the vaccine efficacy of maternal influenza immunisation against maternal and infant PCR-confirmed influenza, duration of protection, and the effect of gestational age at vaccination on vaccine efficacy, birth outcomes, and infant growth up to 6 months of age.

Methods: We did a pooled analysis of three randomised controlled trials done in Nepal (2011-2014), Mali (2011-2014), and South Africa (2011-2013). Pregnant women, gestational age 17-34 weeks in Nepal, 28 weeks or more in Mali, and 20-36 weeks in South Africa, were enrolled. Women were randomly assigned 1:1 to a study group, in which they received trivalent inactivated influenza vaccine (IIV) in all three trials, or a control group, in which they received saline placebo in Nepal and South Africa or quadrivalent meningococcal conjugate vaccine in Mali. Enrolment at all sites was complete by April 24, 2013. Infants and women were assessed for respiratory illness, and samples from those that met the case definition were tested for influenza by PCR testing. Growth measurements, including length and weight, were obtained at birth at all sites, at 24 weeks in South Africa, and at 6 months in Nepal and Mali. The three trials are registered with ClinicalTrials.gov, numbers NCT01430689, NCT01034254, and NCT02465190.

Findings: 10 002 women and 9800 liveborn infants were included. Pooled efficacy of maternal vaccination to prevent infant PCR-confirmed influenza up to 6 months of age was 35% (95% CI 19 to 47). The pooled estimate was 56% (28 to 73) within the first 2 months of life, 39% (11 to 58) between 2 and 4 months, and 19% (-9 to 40) between 4 and 6 months. In women, from enrolment during pregnancy to the end of follow-up at 6 months postpartum, the vaccine was 50% (95% CI 32-63) efficacious against PCR-confirmed influenza. Efficacy was 42% (12 to 61) during pregnancy and 60% (36 to 75) postpartum. In women vaccinated before 29 weeks gestational age, the estimated efficacy was 30% (-2 to 52), and in women vaccinated at or after 29 weeks, efficacy was 71% (50 to 83). Efficacy was similar in infants born to mothers vaccinated before or after 29 weeks gestation (34% [95% CI 12 to 51] vs 35% [11 to 52]). There was no overall association between maternal vaccination and low birthweight, stillbirth, preterm birth, and small for gestational age. At 6 months of age, the intervention and control groups were similar in terms of underweight (weight-for-age), stunted (length-for-age), and wasted (weight-for-length). Median centile change from birth to 6 months of age was similar between the intervention and the control groups for both weight and length.

Interpretation: The assessment of efficacy for women vaccinated before 29 weeks gestational age might have been underpowered, because the point estimate suggests that there might be efficacy despite wide CIs. Estimates of efficacy against PCR-confirmed influenza and safety in terms of adverse birth outcomes should be incorporated into any further consideration of maternal influenza immunisation recommendations.

Funding: Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S2213-2600(19)30479-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284303PMC
June 2020

Intent to obtain pediatric influenza vaccine among mothers in four middle income countries.

Vaccine 2020 06 6;38(27):4325-4335. Epub 2020 May 6.

Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Background: Despite a large burden of influenza in middle income countries, pediatric vaccination coverage remains low. The aims of this study were to (1) describe mothers' knowledge and attitudes about influenza illnesses and vaccination, and (2) identify characteristics associated with mothers' intent to vaccinate their child.

Methods: From 2015 to 2017, infants 0-11 months old in Nicaragua, Philippines, Jordan, and Albania were enrolled from community settings and hospitals. Interviewers administered a questionnaire to their mothers. Mothers of infants aged 6-11 months rated their intention (small-to-moderate vs. large chance) to accept pediatric vaccination if it was offered at no-cost. The importance of knowledge, attitudes, and sociodemographic characteristics in predicting influenza vaccination intention was measured as the mean decrease in Gini index when that factor was excluded from 1000 decision trees in a random forest analysis.

Results: In total, 1,308 mothers were enrolled from the community setting and 3,286 from the hospital setting. Prevalence of at least some knowledge of influenza illness ranged from 34% in Philippines to 88% in Albania (in the community sample), and between 23% in Philippines to 88% in Jordan (in the hospital sample). In the community sample, most mothers in Albania (69%) and Philippines (58%) would accept the influenza vaccine, and these proportions were higher in the hospital sample for all countries except Albania (48%) (P < 0.0001). Perceived vaccine safety (mean decrease in Gini index = 61) and effectiveness (55), and perceived knowledge of influenza vaccine (45) were the most important predictors of influenza vaccination intention in models that also included country and community versus hospital sample.

Conclusion: Intent to vaccinate infants aged 6-11 months in four middle income countries was tied primarily to knowledge of the vaccine and perceptions of vaccine safety and effectiveness. These findings were noted among mothers interviewed in the community and mothers of recently hospitalized infants.
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http://dx.doi.org/10.1016/j.vaccine.2020.04.028DOI Listing
June 2020

A prospective case-control study on the association of Rhinovirus nasopharyngeal viral load and viremia in South African children hospitalized with severe pneumonia.

J Clin Virol 2020 04 11;125:104288. Epub 2020 Feb 11.

Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases Chair, South Africa.

Rhinovirus (RV) role in pathogenesis of severe childhood disease remains controversial. We aimed to explore the association between RV molecular subtyping, nasopharyngeal viral loads and viremia with childhood pneumonia. Nasopharyngeal and blood samples from cases and controls were tested for RV and the 5' non-coding region sequenced. The cases compared to controls had a similar prevalence of RV detection in the nasopharynx (23 % vs. 22 %, P = 0.66), similar RV species distribution (A, B, C = 44 %, 8%, 44 % vs. 48 %, 7%, 38 %; respectively; P = 0.66) and similar viral load (4.0 and 3.7 log10 copies/mL, P = 0.062). However, RV-viremia was 4.01-fold (aOR 95 % CI: 1.26-12.78) more prevalent among cases (7%) than controls (2%), P = 0.019. Furthermore, among cases and controls RV-C was more commonly associated with viremia (14 % and 4%, P = 0.023), than RV-A (2% and 1%; P = 0.529). Thus RV-viremia could be used as a measure for attributing causality to RV in children hospitalized for pneumonia.
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http://dx.doi.org/10.1016/j.jcv.2020.104288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086148PMC
April 2020

Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma? Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting.

Vaccine 2020 03 20;38(11):2435-2448. Epub 2020 Jan 20.

Department of Immunizations, Vaccines and Biologicals, World Health Organization, 20 Avenue Appia, Geneva, Switzerland.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) and hospitalization in infants and children globally. Many observational studies have found an association between RSV LRTI in early life and subsequent respiratory morbidity, including recurrent wheeze of early childhood (RWEC) and asthma. Conversely, two randomized placebo-controlled trials of efficacious anti-RSV monoclonal antibodies (mAbs) in heterogenous infant populations found no difference in physician-diagnosed RWEC or asthma by treatment group. If a causal association exists and RSV vaccines and mAbs can prevent a substantial fraction of RWEC/asthma, the full public health value of these interventions would markedly increase. The primary alternative interpretation of the observational data is that RSV LRTI in early life is a marker of an underlying predisposition for the development of RWEC and asthma. If this is the case, RSV vaccines and mAbs would not necessarily be expected to impact these outcomes. To evaluate whether the available evidence supports a causal association between RSV LRTI and RWEC/asthma and to provide guidance for future studies, the World Health Organization convened a meeting of subject matter experts on February 12-13, 2019 in Geneva, Switzerland. After discussing relevant background information and reviewing the current epidemiologic evidence, the group determined that: (i) the evidence is inconclusive in establishing a causal association between RSV LRTI and RWEC/asthma, (ii) the evidence does not establish that RSV mAbs (and, by extension, future vaccines) will have a substantial effect on these outcomes and (iii) regardless of the association with long-term childhood respiratory morbidity, severe acute RSV disease in young children poses a substantial public health burden and should continue to be the primary consideration for policy-setting bodies deliberating on RSV vaccine and mAb recommendations. Nonetheless, the group recognized the public health importance of resolving this question and suggested good practice guidelines for future studies.
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http://dx.doi.org/10.1016/j.vaccine.2020.01.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049900PMC
March 2020

Immunogenicity and safety of different dosing schedules of trivalent inactivated influenza vaccine in pregnant women with HIV: a randomised controlled trial.

Lancet HIV 2020 02 3;7(2):e91-e103. Epub 2020 Jan 3.

Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, School of Pathology, Faculty of Health Sciences, Johannesburg, South Africa; Department of Science and Technology/National Research Foundation, SARCHI: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa.

Background: Standard-dose, seasonal, trivalent, inactivated influenza vaccine induces moderate-to-low haemagglutination-inhibition antibody responses in people living with HIV. This study assessed the immunogenicity and safety of different dosing schedules of inactivated influenza vaccine in pregnant women living with HIV in South Africa.

Methods: In this double-blind, randomised, controlled trial, we recruited pregnant women with HIV from seven antenatal clinics in Soweto, South Africa. Pregnant women were eligible if they were aged 18-38 years, infected with HIV, and had an estimated gestational age of 12-36 weeks. Women were randomly assigned (1:1:1), using a computer-generated randomisation list, to receive inactivated influenza vaccine containing 15 μg of each of the three seasonal influenza strains for that year, as a single dose, a double dose, or two single doses 1 month apart. Participants and study personnel were masked to group allocation. Haemagglutination-inhibition antibody responses were measured for all groups in the mothers at enrolment and at 1 month after each vaccine dose, and in the single-dose and double-dose groups within 7 days of birth in the neonates. Immunogenicity analyses only included women with visits 28-35 days apart and infants who were born at least 28 days after maternal immunisation. The primary was seroconversion rate to each of the vaccine strains in the mothers 1 month after completion of the dosing schedule, and the primary safety outcomes were frequency of local and systemic reactions. Safety was assessed in mothers and infants until 24 weeks post partum and analysed in all participants who received at least one dose of vaccine. This study is registered with ClinicalTrials.gov, NCT01527825, and is closed to accrual.

Findings: Between Feb 11, and June 6, 2013, 800 pregnant women living with HIV were enrolled and randomly assigned to the single-dose (n=266), double-dose (n=265), or two-single-doses (n=269) group. In the analysable population, seroconversion rates in mothers 1 month after the final vaccine dose were significantly higher in the double-dose group (n=230; ranging from 29% to 65% for the three vaccine strains) than in the single-dose group (n=230; ranging from 18% to 49%; p≤0·019 for the three vaccine strains), but were similar between the two-single-doses group (n=220; ranging from 23% to 52%) and the single-dose group (p≥0·20 for the three vaccine strains). Safety outcomes were similar in the three groups, except for more injection-site reactions in recipients in the double-dose group.

Interpretation: A regimen of double-dose inactivated influenza vaccine gave slightly greater immunogenicity than did a single-dose regimen in pregnant women living with HIV. However, immunogenicity in the double-dose group was still lower than historical data from the same setting in pregnant women without HIV. More immunogenic vaccines are needed for pregnant women living with HIV to enhance transplacental transfer of vaccine-induced protective antibodies to their newborn infants.

Funding: Bill & Melinda Gates Foundation.
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http://dx.doi.org/10.1016/S2352-3018(19)30322-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7167514PMC
February 2020

Laboratory-Confirmed Avian Influenza A(H9N2) Virus Infection, India, 2019.

Emerg Infect Dis 2019 12;25(12):2328-2330

A 17-month-old boy in India with severe acute respiratory infection was laboratory confirmed to have avian influenza A(H9N2) virus infection. Complete genome analysis of the strain indicated a mixed lineage of G1 and H7N3. The strain also was found to be susceptible to adamantanes and neuraminidase inhibitors.
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http://dx.doi.org/10.3201/eid2512.190636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874269PMC
December 2019

State-level estimates of excess hospitalizations and deaths associated with influenza.

Influenza Other Respir Viruses 2020 03 7;14(2):111-121. Epub 2019 Nov 7.

Colorado School of Public Health, Aurora, CO, USA.

Background: National estimates of influenza burden may not reflect state-level influenza activity, and local surveillance may not capture the full burden of influenza.

Methods: To provide state-level information about influenza burden, we estimated excess pneumonia and influenza (P&I) and respiratory and circulatory (R&C) hospitalizations and deaths in Colorado from local hospital discharge records, death certificates, and influenza virus surveillance using negative binomial models.

Results: From July 2007 to June 2016, influenza was associated with an excess of 17 911 P&I hospitalizations (95%CI: 15 227, 20 354), 30 811 R&C hospitalizations (95%CI: 24 344, 37 176), 1,064 P&I deaths (95%CI: 757, 1298), and 3828 R&C deaths (95%CI: 2060, 5433). There was a large burden of influenza A(H1N1) among persons aged 0-64 years, with high median seasonal rates of excess hospitalization among persons aged 0-4 years. Persons aged ≥65 years experienced the largest numbers and highest median seasonal rates of excess hospitalization and death associated with influenza A (H3N2). The burden of influenza B was generally lower, with elevated median seasonal rates of excess hospitalization among persons aged 0-4 years and ≥65 years.

Conclusions: These findings complement existing influenza surveillance. Periodic state-level estimates of influenza disease burden may be useful for setting state public health priorities and planning prevention and control initiatives.
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http://dx.doi.org/10.1111/irv.12700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040963PMC
March 2020

Approaches to use the WHO respiratory syncytial virus surveillance platform to estimate disease burden.

Influenza Other Respir Viruses 2020 11 8;14(6):615-621. Epub 2019 Oct 8.

Global Influenza Program, World Health Organization, Geneva, Switzerland.

The World Health Organization (WHO) recently completed the first phase of a RSV surveillance pilot study in fourteen countries (two to three in each WHO region) building on the Global Influenza Surveillance and Response System (GISRS). This active surveillance strategy had several objectives including understanding RSV-related health burden in a variety of settings. A range of approaches can be used to estimate disease burden; most approaches could not be applied by participating countries in the WHO surveillance pilot. This article provides the recommendations made by WHO for strengthening and expanding the scope of the RSV surveillance in the next phase to enable burden estimation.
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http://dx.doi.org/10.1111/irv.12667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578280PMC
November 2020

Underdetection of laboratory-confirmed influenza-associated hospital admissions among infants: a multicentre, prospective study.

Lancet Child Adolesc Health 2019 11 3;3(11):781-794. Epub 2019 Sep 3.

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.

Background: Since influenza often presents non-specifically in infancy, we aimed to assess the extent to which existing respiratory surveillance platforms might underestimate the frequency of severe influenza disease among infants.

Methods: The Influenza and Respiratory Syncytial Virus in Infants (IRIS) study was a prospective observational study done at four hospitals in Albania, Jordan, Nicaragua, and the Philippines. We included acutely ill infants aged younger than 1 year admitted to hospital within 10 days or less of illness onset during two influenza seasons (2015-16 and 2016-17) in Albania, Jordan, and Nicaragua, and over a continuous 34 week period (2015-16) in the Philippines. We assessed the frequency of influenza virus infections by real-time RT-PCR (rRT-PCR) and serology. The main study outcome was seroconversion, defined as convalescent antibody titres more than or equal to four-fold higher than acute sera antibody titres, and convalescent antibody titres of 40 or higher. Seroconverison was confirmed by haemagglutination inhibition assay for influenza A viruses, and by hemagglutination inhibition assay and microneutralisation for influenza B viruses.

Findings: Between June 27, 2015, and April 21, 2017, 3634 acutely ill infants were enrolled, of whom 1943 were enrolled during influenza seasons and had complete acute-convalescent pairs and thus were included in the final analytical sample. Of the 1943 infants, 94 (5%) were influenza-positive by both rRT-PCR and serology, 58 (3%) were positive by rRT-PCR-only, and 102 (5%) were positive by serology only. Seroconversion to at least one of the influenza A or B viruses was observed among 196 (77%) of 254 influenza-positive infants. Of the 254 infants with influenza virus, 84 (33%) only had non-respiratory clinical discharge diagnoses (eg, sepsis, febrile seizures, dehydration, or other non-respiratory viral illness). A focus on respiratory diagnoses and rRT-PCR-confirmed influenza underdetects influenza-associated hospital admissions among infants by a factor of 2·6 (95% CI 2·0-3·6). Findings were unchanged when syndromic severe acute respiratory infection criteria were applied instead of clinical diagnosis.

Interpretation: If the true incidence of laboratory-confirmed influenza-associated hospital admissions among infants is at least twice that of previous estimates, this substantially increases the global burden of severe influenza and expands our estimates of the preventive value of maternal and infant influenza vaccination programmes.

Funding: US Centers for Disease Control and Prevention.
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http://dx.doi.org/10.1016/S2352-4642(19)30246-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029431PMC
November 2019

Trivalent influenza vaccination randomized control trial of pregnant women and adverse fetal outcomes.

Vaccine 2019 08 19;37(36):5397-5403. Epub 2019 Jul 19.

Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand, York Road, Parktown, Johannesburg 2193, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, York Road, Parktown, Johannesburg 2193, South Africa; National Institute for Communicable Diseases: a division of National Health Laboratory Service, Centre for Vaccines and Immunology, 1 Modderfontein Road, Sandringham, Johannesburg, South Africa.

Introduction: The purpose of this study was to evaluate the association of influenza vaccine during pregnancy and adverse fetal outcomes. Preventing fetal death, low birth weight, small for gestational age birth and preterm birth are important potential effects of antenatal maternal influenza immunization for which there are conflicting data.

Materials And Methods: A double-blind, randomized, placebo-controlled clinical trial of trivalent inactivated influenza vaccine was conducted in South Africa from March 2011 until after the 2012 influenza season when the infants born had reached the age of 24 weeks. Mothers were administered the vaccine or placebo during pregnancy at a gestation of 20 to 36 weeks. A comparison of rates of fetal death, low birth weight, small for gestational age birth, and preterm birth, between vaccinated and placebo groups was made. Fetal outcome differences between the groups were measured using Student's t-tests, vaccine efficacy with 95% confidence intervals, and Poisson regression for incidence rates. All analyses except fetal death excluded mothers who were administered vaccine or placebo after 34 weeks gestational age.

Results: There were 2116 HIV-uninfected pregnant women age 18 to 38 years in the trial; 2005 infants were born to mothers where vaccine or placebo had been administered ≥ 14 days prior to delivery, and there were 6 miscarriages and 23 stillbirths. There was no significant vaccine efficacy (with [95% confidence interval]) on fetal death (-21.2% [-150.8, 41.4]), low birth weight (-11.1% [-42.3, 12.5]), small for gestational age birth (-9.9% [-35.6, 11.0]), or preterm birth (-21.3% [-60.5, 8.3]). Neither was vaccine efficacy demonstrated when the analysis was restricted to infants of mothers who were exposed to an influenza season (1832 outcomes available).

Conclusion: We did not find a beneficial effect of trivalent inactivated influenza vaccine during pregnancy on adverse fetal outcomes.
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http://dx.doi.org/10.1016/j.vaccine.2019.07.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6694200PMC
August 2019

Molecular Subtyping of Human Rhinovirus in Children from Three Sub-Saharan African Countries.

J Clin Microbiol 2019 09 26;57(9). Epub 2019 Aug 26.

Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases Chair, Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa.

The pathogenesis of human rhinovirus (HRV) during severe respiratory disease remains undefined; thus, we aimed to explore the relationship between the HRV molecular subtyping results obtained during severe and asymptomatic childhood infections. Nasopharyngeal/oropharyngeal swabs from children (1 to 59 months of age) hospitalized with pneumonia and from age-frequency-matched controls were collected between August 2011 and August 2013. Swabs were tested for respiratory pathogens, including HRV, using quantitative real-time PCR assays. HRV-positive samples were sequenced for phylogenetic analysis by targeting the 5' noncoding region (5'NCR). Our data showed that there were no differences in the prevalence of HRV detection among cases and controls (21% versus 20%, 0.693); however, among children 13 to 59 months old, HRV detection was more often case associated (21% versus 16%; 0.009), with the results mainly driven by HRV-C (12% versus 7%; 0.001). Overall, there were no differences in the results of molecular subtyping of the HRV species prevalence among cases (for HRV-A, 48%; for HRV-B, 7%; for HRV-C, 45%) and controls (for HRV-A, 45%; for HRV-B, 10%; for HRV-C, 45% [0.496]). Those with pneumonia and HRV-C were older (12.1 versus 9.4 months, 0.033) and more likely to present with wheeze (35% versus 25%, 0.031) than those with HRV-A cases. Thus, the rate of HRV detection was high, with similar degrees of genetic diversity among cases and controls, confounding the interpretation of the presence of HRV in nasopharyngeal samples for attribution of a causal role in the pathogenesis of severe pneumonia in infants. However, among children 13 to 59 months of age, HRV detection, in particular, HRV-C detection, was associated with case status, especially among children with wheezing disease.
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http://dx.doi.org/10.1128/JCM.00723-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711929PMC
September 2019

Otitis media related hearing loss in Indonesian school children.

Int J Pediatr Otorhinolaryngol 2019 Oct 19;125:44-50. Epub 2019 Jun 19.

University of Colorado School of Medicine, Aurora, CO, USA; Colorado School of Public Health, Aurora, CO, USA. Electronic address:

Objective: There are scant recent studies from low middle-income countries that investigate the impact of otitis media (OM) on hearing loss (HL) in school children.

Methods: This was a prospective epidemiological survey conducted by otorhinolaryngologists and audiologists in a sample of 7005 public school children (6-15 years) from 6 urban and rural sub-districts, in Indonesia. Children with otoscopic abnormalities or who failed a hearing-screening test conducted at school, underwent diagnostic audiometry and tympanometry.

Results: OM was detected in 172 children (2.5%), acute otitis media - AOM (17%), otitis media with effusion - OME (15%), and chronic suppurative otitis media - CSOM (67%). The overall rate of HL in the school children was 181/10,000, which was almost three-fold higher in rural (273/10,000) than urban areas 92.6/10,000. OME accounted for much of the mild HL, while CSOM accounted for most of the moderate HL. There was a significantly higher rate of OM related HL in rural areas (116.2/10,000), than in urban areas (47.4/10,000), p = 0.002. OM related disabling HL was found at a rate of 44.2/10,000, mostly due to CSOM (37.1/10,000).

Conclusion: Otitis media contributed to 57% of all HL in school children, and posed a significant burden on Indonesian school children. Most of the disabling HL was due to CSOM. Efforts to find these children and offer ear and hearing care are important.
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http://dx.doi.org/10.1016/j.ijporl.2019.06.019DOI Listing
October 2019

Long-term Assessment of Healthcare Utilization 5 Years After Respiratory Syncytial Virus Infection in US Infants.

J Infect Dis 2020 03;221(8):1256-1270

Regeneron, Tarrytown, New York.

Background: Respiratory syncytial virus (RSV) is the primary cause of respiratory tract infections in infants; however, current burden estimates report only the short-term effects of acute infection.

Methods: Infants with RSV infection and ≥24 months of continuous enrollment were retrospectively identified from the Truven MarketScan database (1 January 2004-30 September 2015). Exposed infants (n = 38 473) were propensity score matched to nonexposed controls (n = 76 825) by baseline characteristics and gestational age. Five-year cumulative all-cause, asthma/wheezing, and respiratory event-related hospitalization rates and physician and emergency department healthcare-resource utilization rates were assessed.

Results: During follow-up, RSV-infected cohorts had higher average all-cause cumulative hospitalization rates, compared with controls, with values of 79.9 hospitalizations/100 patient-years (95% confidence interval [CI], 41.7-118.2) for 213 early premature infants (P < .001), 18.2 hospitalizations/100 patient-years (95% CI, .8-35.7) for 397 premature infants (P = .04), 34.2 hospitalizations/100 patient-years (95% CI, 29.1-39.2) for 4446 late premature infants (P < .001), and 16.1 hospitalizations/100 patient-years (95% CI, 14.9-17.4) for 33 417 full-term infants (P < .001). Cumulative rates of physician and emergency department visits were also higher for RSV-infected infants. Asthma/wheezing accounted for 10%-18% of total 5-year physician visits.

Conclusions: Infant RSV infection has a significant long-term healthcare-resource utilization impact across gestational ages for at least 5 years after infection, most of it in the first 2 years. Systematically collecting healthcare-resource utilization data will be important for cost-effectiveness evaluations of RSV interventions in planned or ongoing trials.
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http://dx.doi.org/10.1093/infdis/jiz278DOI Listing
March 2020

SENTINEL1: Two-Season Study of Respiratory Syncytial Virus Hospitalizations among U.S. Infants Born at 29 to 35 Weeks' Gestational Age Not Receiving Immunoprophylaxis.

Am J Perinatol 2020 03 16;37(4):421-429. Epub 2019 Apr 16.

AstraZeneca, Gaithersburg, Maryland.

Objective: The SENTINEL1 observational study characterized confirmed respiratory syncytial virus hospitalizations (RSVH) among U.S. preterm infants born at 29 to 35 weeks' gestational age (wGA) not receiving respiratory syncytial virus (RSV) immunoprophylaxis (IP) during the 2014 to 2015 and 2015 to 2016 RSV seasons.

Study Design: All laboratory-confirmed RSVH at participating sites during the 2014 to 2015 and 2015 to 2016 RSV seasons (October 1-April 30) lasting ≥24 hours among preterm infants 29 to 35 wGA and aged <12 months who did not receive RSV IP within 35 days before onset of symptoms were identified and characterized.

Results: Results were similar across the two seasons. Among infants with community-acquired RSVH ( = 1,378), 45% were admitted to the intensive care unit (ICU) and 19% required invasive mechanical ventilation (IMV). There were two deaths. Infants aged <6 months accounted for 78% of RSVH observed, 84% of ICU admissions, and 91% requiring IMV. Among infants who were discharged from their birth hospitalization during the RSV season, 82% of RSVH occurred within 60 days of birth hospitalization discharge.

Conclusion: Among U.S. preterm infants 29 to 35 wGA not receiving RSV IP, RSVH are often severe with almost one-half requiring ICU admission and about one in five needing IMV.
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http://dx.doi.org/10.1055/s-0039-1681014DOI Listing
March 2020

Economic-Burden Trajectories in Commercially Insured US Infants With Respiratory Syncytial Virus Infection.

J Infect Dis 2020 03;221(8):1244-1255

Real World Evidence, Pharmerit International, Bethesda, Maryland.

Background: This study evaluates the long-term respiratory syncytial virus (RSV) burden among preterm and full-term infants in the United States.

Methods: Infants with birth hospitalization claims and ≥24 months of continuous enrollment were retrospectively identified in the Truven MarketScan Commercial Claims and Encounters database for the period 1 January 2004-30 September 2015. Infants with RSV infection in the first year of life (n = 38 473) were matched to controls (n = 76 825), and remaining imbalances in the number of individuals in each group were adjusted using propensity score methods. All-cause, respiratory-related, and asthma/wheezing-related 5-year average cumulative costs were measured.

Results: Early premature (n = 213), premature (n = 397), late premature (n = 4446), and full-term (n = 33 417) RSV-infected infants were matched to 424, 791, 8875, and 66 735 controls, respectively. After 2 years since RSV diagnosis, all-cause cumulative costs for RSV-infected infants as compared to those for controls increased by $22 081 (95% confidence interval [CI], -$5800-$42 543) for early premature infants, by $14 034 (95% CI, $5095- $22 973) for premature infants, by $10 164 (95% CI, $8835-$11 493) for late premature infants, and by $5404 (95% CI, $5110-$5698) for full-term infants. The 5-year RSV burden increased to $39 490 (95% CI, $18 217-$60 764), $23 160 (95% CI, $13 002-$33 317),$13 755 (95% CI, $12 097-$15 414), and $6631 (95% CI, $6060-$7202), respectively. The RSV burden was higher when stratified by inpatient and outpatient setting and respiratory-related and asthma/wheezing-related costs.

Conclusions: The RSV burden extends across cost domains and prematurity, with the greatest burden incurred by the second year of follow-up. Findings are useful in determining the cost-effectiveness of RSV therapies in development.
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http://dx.doi.org/10.1093/infdis/jiz160DOI Listing
March 2020

Lay Field-worker-Led School Health Program for Primary Schools in Low- and Middle-Income Countries.

Pediatrics 2019 04 14;143(4). Epub 2019 Mar 14.

Center for Global Health, Colorado School of Public Health, Aurora, Colorado.

Background And Objectives: School health programs are frequently attempted in low- and/or middle-income countries; however, programmatic scope and reach is limited by human resource constraints. We sought to determine if trained community members could implement a school health program that improved outcomes in rural primary schools in India.

Methods: This was a mixed-methods, stepped-wedge, cluster-controlled study of schools pragmatically assigned to receive a multicomponent, comprehensive school health program delivered by lay field-workers.

Results: All students in 22 primary schools (9 government schools and 13 low-cost private schools) participated in this study. A total of 3033 student-years were included in the analysis (2100 student-years in the intervention period and 933 student-years in the control period). Qualitative feedback was collected from 38 teachers, 49 parents, and 4 field-workers. In low-cost private schools, the diarrhea incidence was lower in students receiving the intervention (incidence rate ratio 0.58; 95% confidence interval [CI] 0.47 to 0.71; < .001). There was no difference in diarrhea incidence for students in government schools (incidence rate ratio 0.87; 95% CI 0.68 to 1.12; = .29). Health-knowledge acquisition was higher in intervention schools (mean difference 12.6%; 95% CI 8.8 to 16.4; < .001) and similar in both school types. Intervention coverage rates were high (mean 93.9%; SD 2.0%), and performance assessment scores indicated fidelity (mean 3.45; SD 0.69). Stakeholders revealed favorable perceptions of the field-workers and high levels of perceived impact.

Conclusions: Lay field-worker-led school health programs offer a promising alternative for improving school health delivery in resource-constrained settings.
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http://dx.doi.org/10.1542/peds.2018-0975DOI Listing
April 2019

Impaired Transplacental Transfer of Respiratory Syncytial Virus-neutralizing Antibodies in Human Immunodeficiency Virus-infected Versus -uninfected Pregnant Women.

Clin Infect Dis 2019 06;69(1):151-154

Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, Johannesburg, South Africa.

Human immunodeficiency virus (HIV)-exposed, uninfected infants have higher risks of respiratory syncytial virus-associated hospitalization than HIV-unexposed infants. Despite similar neutralizing antibody titers between HIV-infected and -uninfected women, maternal HIV infection and hypergammaglobulinemia were independently associated with lower titers in newborns. Maternal hypergammaglobulinemia was associated with lower cord-to-maternal antibody ratio.
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http://dx.doi.org/10.1093/cid/ciy1071DOI Listing
June 2019

Detection of parvovirus B19 in selected high-risk patient groups & their phylogenetic & selection analysis.

Indian J Med Res 2018 04;147(4):391-399

Sri Sakthi Amma Institute of Biomedical Research, Sri Narayani Hospital & Research Centre, Vellore, India.

Background & Objectives: Human parvovirus B19V (B19V) is known to be associated with erythema infectiosum commonly in children, aplastic crisis, especially in persons with underlying haemolytic disorders, hydrops fetalis in pregnancies and arthritis. This cross-sectional study was aimed to determine the presence of B19V infection in childhood febrile illnesses, association of B19V with arthropathies and in adult patients with end-stage renal disease (ESRD) on dialysis. The genetic diversity among the sequences was also analysed.

Methods: A nested polymerase chain reaction (nPCR) assay was used for B19V DNA targeting VP1/VP2 region and used for testing 618 patients and 100 healthy controls. Phylogenetic analysis on nucleotide and amino acid sequences was carried out to compare our sequences with other Indian strains and global strains.

Results: Among 618 samples tested, seven (1.13%) were found positive. The phylogenetic analysis revealed that all the seven sequences belonged to genotype 1 and showed low genetic diversity. The clustering pattern of seven sequences was similar both by nucleotide and by predicted amino acid sequences. The fixed effects likelihood analysis showed no positive or negatively selected sites.

Interpretation & Conclusions: Seven samples (4 from non-traumatic arthropathies, 2 from patients with ESRD and 1 from febrile illness patient) were found positive by nPCR. When our seven sequences were compared with global strains, the closest neighbour was other Indian strains followed by the Tunisian strains.
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Source
http://dx.doi.org/10.4103/ijmr.IJMR_241_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057248PMC
April 2018