hMPV is a common cause of medically attended ARI (MA-ARI) in US children aged < 5 years, but few data are available on disease burden in AI/AN children. For respiratory syncytial virus (RSV), another common cause of pediatric respiratory illness, hospitalization rates in AI/AN children < 5 years historically have been higher than for the general US population < 5 years (17-40/1000 in some remote AI/AN communities versus 4-6/1000). We describe the epidemiology of medically attended hMPV-associated ARI in AI/AN children and estimate incidence rates of hMPV-associated hospitalizations. We conducted population-based surveillance for MA-ARI in hospitalized and outpatient AI/AN children aged < 5 years in the Southwest US (Navajo Nation and White Mountain Apache Tribal lands) and Alaska (Yukon Kuskokwim Delta and Anchorage) during November 2019-May 2024. Nasal swabs were tested by PCR for hMPV and RSV. We described the seasonality of hMPV and RSV detection and compared the clinical presentation of children with hMPV-positive versus hMPV-negative MA-ARI using Fisher’s exact test and Wilcoxon rank sum test. We used Poisson regression to estimate annual hMPV-associated hospitalization incidence per 1000 children stratified by age and site. hMPV seasonality varied regionally but circulation typically followed the onset of the RSV season; the COVID-19 pandemic disrupted circulation during 2021 (Fig). Among the 2561 (90%) of 2836 enrollees with hMPV testing, hMPV was detected in 14% (1373/1591) of swabs from inpatient children and 8% (79/970) of swabs from outpatient children (Table 1). Clinical characteristics were generally similar in children with hMPV-positive compared to hMPV-negative MA-ARI. The incidence of HMPV-associated ARI hospitalization among children < 5 years ranged from 0-16.0/1000 and age-group patterns varied by site and year (Table 2). hMPV-associated hospitalization incidence rates in AI/AN children < 5 years were lower than historical RSV-associated hospitalization rates in these same communities but similar to or greater than historical RSV rates in the general US child population. These findings provide a baseline for hMPV disease burden for assessments of future prevention products. All Authors: No reported disclosures

Nirsevimab is recommended to prevent severe respiratory syncytial virus (RSV)-associated illness among American Indian/Alaska Native (AI/AN) children <20 months of age. In a test-negative case-control analysis among 291 AI/AN children hospitalized during the 2023-2024 season, nirsevimab was 86.0% and 87.9% effective among children entering their first and second RSV seasons, respectively.

American Indian/Alaska Native (AI/AN) peoples experienced some of the highest rates of coronavirus disease 2019 (COVID-19) disease in the United States. However, there are limited data on COVID-19 vaccine effectiveness in this population. We performed a test-negative case‒control study using electronic health record data to evaluate the effectiveness of the original three FDA-authorised vaccines to prevent COVID-19-associated hospitalisations among AI/AN adults during 2021-2022. COVID-19 vaccines were effective in preventing COVID-19-associated hospitalisation, intensive care unit admission, mechanical ventilation and death in this population. However, vaccine effectiveness waned over time and during the post-Omicron variant time period. Booster vaccination proved effective during a period when the Omicron variant was circulating. Waning effectiveness with time and the introduction of new variants supports the need to stay up-to-date with SARS-CoV-2 vaccination. Evaluating vaccine effectiveness using electronic health records proved to be a useful tool during a pandemic.

COVID-19 causes significant morbidity in the USA, particularly among American Indian/Alaska Native (AI/AN) persons. Estimates of COVID-19 burden among AI/AN communities are needed to identify health outcome disparities and inform prevention strategies, but under-ascertainment of AI/AN status in national data may result in underestimation of COVID-19 disease burden. Surveillance for acute respiratory illness was conducted among AI/AN persons at eight healthcare facilities in Arizona and Alaska to identify COVID-19-associated hospitalizations and outpatient visits. Weekly and annual incidence rates of COVID-19-associated hospitalizations per 100,000 persons were calculated overall and by site and age. Risk factors for COVID-19-associated hospitalizations (versus outpatient visits) were assessed. From January 2021 to December 2022, 1159 COVID-19-associated hospitalizations were identified. Incidence rates were 439.8 per 100,000 in 2021 and 332.6 per 100,000 in 2022 and highest among adults ≥ 65 years at all sites. Compared to national estimates from 2021 to 2022, incidence rates by time and age were similar among older adults, whereas incidence rates among AI/AN children were over twice as high. Among adults, older age, chronic lung disease, chronic kidney disease, and diabetes increased the risk of hospitalization; frequent mask use outside the home and COVID-19 vaccination were protective, particularly if vaccinated within the past year. Among children, younger age and heart conditions increased the risk of hospitalization. The findings demonstrate a substantial burden of COVID-19 in AI/AN persons and provide critically needed data regarding the risks for severe outcomes. AI/AN children experience a disproportionate burden of COVID-19 disease.

Background: Haemophilus influenzae (Hi) can cause severe disease in children. This study aimed to identify risk factors related to invasive Hi disease in Alaska children and evaluate carriage in people around them. Methods: From 2005 to 2011, we investigated episodes of invasive, typeable Hi disease in Alaska children <10 years old. Three age-matched control children were enrolled for each case-patient. We evaluated oropharyngeal Hi carriage in people in close contact with Hi case-patients (contacts) as well as control children and their household members. Individual and household risk factors for illness and carriage were evaluated using questionnaires and chart reviews. Results: Thirty-eight of 44 (86%) children with invasive, typeable Hi disease were recruited: 20 Hi serotype a (53%), 13 serotype b (Hib) (34%) and 5 serotype f (13%). Children with the invasive Hi disease were more likely than controls to have underlying health problems (67% vs. 24%, P = 0.001), other carriers of any Hi in their household (61% vs. 15%, P < 0.001), and inadequate Hib vaccination (26% vs. 9%, P = 0.005). People who carried Hi were younger than noncarriers (mean 12.7 vs. 18.0 years, P = 0.008). The carriage was clustered within case-patient households, with carriage in 19% of household contacts, while only 6.3% of nonhousehold contacts and 5.5% of noncontacts carried the Hi serotype of interest (P < 0.001). Conclusions: Factors associated with invasive Hi disease in children included underlying health problems, household carriage and inadequate Hib vaccination. The high level of carriage in case-patient households is important to consider when evaluating treatment and prophylaxis strategies.

Background: Persistent human papillomavirus (HPV) infection can cause anogenital and oropharyngeal cancers. Many HPV infections and HPV-associated cancers are vaccine -preventable. Studies suggest long-term persistence of vaccine -induced antibodies. However, data are limited among Alaska Native people. Methods: During 2011-2014, we enrolled Alaska Native children aged 9-14 years who received a 3 -dose series of quadrivalent HPV vaccine (4vHPV). We collected sera at 1 month and 1, 2, 3, and 5 years post -vaccination to evaluate trends in type -specific immunoglobulin G antibody concentrations for the 4vHPV types (HPV 6/11/16/ 18). Results: All participants (N = 469) had detectable antibodies against all 4vHPV types at all timepoints postvaccination. For all 4vHPV types, antibody levels peaked by 1 month post -vaccination and gradually declined in subsequent years. At 5 years post -vaccination, antibody levels were higher among children who received 4vHPV at a younger age. Conclusions: Alaska Native children maintained antibodies against all 4vHPV types at 5 years post -vaccination.

Alaska Native and American Indian children experience frequent respiratory illness. Indoor air quality is associated with the severity and frequency of respiratory infections in children. High efficiency particulate air (HEPA) purifiers effectively improve indoor air quality and may protect respiratory health. In 2019, the Yukon-Kuskokwim Health Corporation implemented a pilot programme that provided education and HEPA purifiers to households of children with chronic lung conditions. The team evaluated HEPA purifier acceptability and use by interviewing representatives from 11 households that participated in the pilot programme. All interviewees reported improvement in their child's health, and some believed that the health of other household members was also improved because of the HEPA purifier. Interviewees reported that the HEPA purifiers were easy to use, quiet, and not expensive to run. Five of 11 households were still using the HEPA purifier at the time of the interview, which was about three years after receipt of the unit. The most common reasons for discontinuing use were equipment failure and lack of replacement filter, suggesting that programme support could increase sustainability. Our evaluation suggests that HEPA purifiers are acceptable and feasible for use in rural Alaska Native households.

Otitis media-associated outpatient visits among American Indians/Alaska Natives children <5 years old decreased by 52% (100 to 48 per 100 children per year) from 2003 to 2019. Otitis media visits decreased by another 50% from 2019 to 2020, but rebounded between 2020 and 2021 back to a rate similar to 2019.

Abstract Background Acute viral bronchiolitis is the most common reason for hospitalization of infants in the USA. Infants hospitalized for bronchiolitis are at high risk for recurrent respiratory symptoms and wheeze in the subsequent year, and longer-term adverse respiratory outcomes such as persistent childhood asthma. There are no effective secondary prevention strategies. Multiple factors, including air pollutant exposure, contribute to risk of adverse respiratory outcomes in these infants. Improvement in indoor air quality following hospitalization for bronchiolitis may be a prevention opportunity to reduce symptom burden. Use of stand-alone high efficiency particulate air (HEPA) filtration units is a simple method to reduce particulate matter ≤ 2.5 µm in diameter (PM2.5), a common component of household air pollution that is strongly linked to health effects. Methods BREATHE is a multi-center, parallel, double-blind, randomized controlled clinical trial. Two hundred twenty-eight children < 12 months of age hospitalized for the first time with bronchiolitis will participate. Children will be randomized 1:1 to receive a 24-week home intervention with filtration units containing HEPA and carbon filters (in the child’s sleep space and a common room) or to a control group with units that do not contain HEPA and carbon filters. The primary objective is to determine if use of HEPA filtration units reduces respiratory symptom burden for 24 weeks compared to use of control units. Secondary objectives are to assess the efficacy of the HEPA intervention relative to control on (1) number of unscheduled healthcare visits for respiratory complaints, (2) child quality of life, and (3) average PM2.5 levels in the home. Discussion We propose to test the use of HEPA filtration to improve indoor air quality as a strategy to reduce post-bronchiolitis respiratory symptom burden in at-risk infants with severe bronchiolitis. If the intervention proves successful, this trial will support use of HEPA filtration for children with bronchiolitis to reduce respiratory symptom burden following hospitalization. Trial registration NCT05615870. Registered on November 14, 2022.

OBJECTIVES:American Indian and Alaska Native (AI/AN) infants historically experienced a disproportionate burden of invasive Haemophilus influenzae type b (Hib) disease, especially early in life. PedvaxHIB vaccine is preferentially recommended for AI/AN infants because it elicits protective antibody levels postdose 1. Vaxelis, a hexavalent vaccine that contains the same Hib conjugate as PedvaxHIB but at lower concentration, is recommended for US children, but postdose 1 Hib immunogenicity data are needed to inform whether a preferential recommendation should be made for AI/AN infants. METHODS:We conducted a phase IV randomized, open-label, noninferiority trial comparing postdose 1 immunogenicity of Vaxelis to PedvaxHIB in AI/AN infants. Participants were randomized to receive a primary series of PedvaxHIB or Vaxelis. Serum samples collected 30 days postdose 1 were tested for anti-Hib immunoglobulin G antibody by enzyme-linked immunosorbent assay. The anti-Hib immunoglobulin G geometric mean concentration (GMC) ratio (Vaxelis/PedvaxHIB) was estimated by constrained longitudinal data analysis. Noninferiority was defined a priori as the lower bound of the 95% confidence interval (CI) of the GMC ratio ≥0.67. RESULTS:A total of 327 of the 333 infants enrolled in the study were included in the per-protocol analysis. The postdose 1 anti-Hib GMC was 0.41 µg/mL (95% CI 0.33-0.52) in the Vaxelis group (n = 152) and 0.39 µg/mL (95% CI 0.31-0.50) in the PedvaxHIB group (n = 146). The constrained longitudinal data analysis GMC ratio was 1.03 (95% CI 0.76-1.39). CONCLUSIONS:Postdose 1 immunogenicity of Vaxelis was noninferior to PedvaxHIB. Our findings support the use of Vaxelis in AI/AN children, a population with elevated risk of Hib disease.

Respiratory syncytial virus (RSV) is a leading cause of hospitalization among young children. Historically, American Indian and Alaska Native (AI/AN) children have experienced high rates of RSV-associated hospitalization. In August 2023, a preventive monoclonal antibody (nirsevimab) was recommended for all infants aged <8 months (born during or entering their first RSV season) and for children aged 8-19 months (entering their second RSV season) who have increased risk for severe RSV illness, including all AI/AN children. This evaluation in Alaska's Yukon-Kuskokwim Delta region estimated nirsevimab effectiveness among AI/AN children in their first or second RSV seasons during 2023-2024. Among 472 children with medically attended acute respiratory illness (ARI), 48% overall had received nirsevimab >= 7 days earlier (median = 91 days before the ARI-related visit). For children in their first RSV season (292), nirsevimab effectiveness was 76% (95% CI = 42%-90%) against medically attended RSV illness and 89% (95% CI = 32%-98%) against RSV hospitalization. For children in their second RSV season (180), effectiveness against medically attended RSV illness was 88% (95% CI = 48%-97%). Nirsevimab is effective for preventing severe RSV illness among infants entering their first RSV season and children entering their second season with increased risk for severe RSV, including all AI/AN children.

Cough is the most common complaint among primary healthcare visits in pediatrics.1Irwin R.S. Richardson N.D. Patient-focused care: using the right tools.Chest. 2006; 130: 73S-82SAbstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar,2Goldsobel A.B. Chipps B.E. Cough in the pediatric population.J Pediatr. 2010; 156: 352-358Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar Chronic cough in young children typically is defined as cough lasting 4 weeks.3Marchant J.M. Newcombe P.A. Juniper E.F. Sheffield J.K. Stathis S.L. Chang A.B. What is the burden of chronic cough for families?.Chest. 2008; 134: 303-309Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar,4Bailey E.J. Morris P.S. Kruske S.G. Chang A.B. 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Cough quality in children: a comparison of subjective vs. bronchoscopic findings.Respir Res. 2005; 6: 3Crossref PubMed Scopus (119) Google Scholar Research varies on how good parents are at noting dry vs wet cough.7Chang A.B. Gaffney J.T. Eastburn M.M. Faoagali J. Cox N.C. Masters I.B. Cough quality in children: a comparison of subjective vs. bronchoscopic findings.Respir Res. 2005; 6: 3Crossref PubMed Scopus (119) Google Scholar,8Donnelly D. Everard M.L. 'Dry' and 'wet' cough: how reliable is parental reporting?.BMJ Open Respir Res. 2019; 6e000375Crossref PubMed Scopus (11) Google Scholar Guidelines recommend treating chronic wet cough of 4 weeks or longer with antibiotics.5Chang A.B. Oppenheimer J.J. Weinberger M.M. Rubin B.K. Grant C.C. Weir K. et al.Management of children with chronic wet cough and protracted bacterial bronchitis: CHEST guideline and expert panel report.Chest. 2017; 151: 884-890Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar,9Chang A.B. Oppenheimer J.J. Irwin R.S. Managing chronic cough as a symptom in children and management algorithms: CHEST guideline and expert panel report.Chest. 2020; 158: 303-329Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar A common cause of chronic wet cough is protracted bacterial bronchitis (PBB), a bacterial infection of the lower airways leading to a chronic wet cough.10Chang A.B. Robertson C.F. Van Asperen P.P. Glasgow N.J. Mellis C.M. Masters I.B. et al.A multicenter study on chronic cough in children : burden and etiologies based on a standardized management pathway.Chest. 2012; 142: 943-950Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar, 11Marchant J. Masters I.B. Champion A. Petsky H. Chang A.B. Randomised controlled trial of amoxycillin clavulanate in children with chronic wet cough.Thorax. 2012; 67: 689-693Crossref PubMed Scopus (117) Google Scholar, 12Lewis T.C. Stout J.W. Martinez P. Morray B. White L.C. Heckbert S.R. et al.Prevalence of asthma and chronic respiratory symptoms among Alaska Native children.Chest. 2004; 125: 1665-1673Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar, 13Lau G.T.Y. Laird P. Stevenson P.G. Schultz A. Frequency of protracted bacterial bronchitis and management pre-respiratory referral.J Paediatr Child Health. 2022; 58: 97-103Crossref PubMed Scopus (7) Google Scholar The gold standard for diagnosis of PBB is flexible bronchoscopy with lavage to demonstrate inflammation and bacterial overgrowth (laboratory PBB), but this procedure is invasive and requires travel to specialty centers.14Marchant J.M. Masters I.B. Taylor S.M. Cox N.C. Seymour G.J. Chang A.B. Evaluation and outcome of young children with chronic cough.Chest. 2006; 129: 1132-1141Abstract Full Text Full Text PDF PubMed Scopus (301) Google Scholar Accordingly, guidelines supported by clinical trials from specialty centers in Australia recommend empiric antibiotics without bronchoscopy and lavage if there is no evidence for other causes of cough for treatment.5Chang A.B. Oppenheimer J.J. Weinberger M.M. Rubin B.K. Grant C.C. Weir K. et al.Management of children with chronic wet cough and protracted bacterial bronchitis: CHEST guideline and expert panel report.Chest. 2017; 151: 884-890Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar,6Kantar A. Chang A.B. Shields M.D. Marchant J.M. Grimwood K. Grigg J. et al.ERS statement on protracted bacterial bronchitis in children.Eur Respir J. 2017; 501602139Crossref PubMed Scopus (104) Google Scholar,15Paul S.P. Sanapala S. Bhatt J.M. Recognition and management of children with protracted bacterial bronchitis.Br J Hosp Med. 2015; 76: 398-404Crossref PubMed Scopus (5) Google Scholar,16Chang A.B. Upham J.W. Masters I.B. Redding G.R. Gibson P.G. Marchant J.M. et al.Protracted bacterial bronchitis: the last decade and the road ahead.Pediatr Pulmonol. 2016; 51: 225-242Crossref PubMed Scopus (118) Google Scholar Other causes of chronic cough that vary by region around the globe include asthma, sinusitis, upper airway cough syndrome, gastroesophageal reflux disease, infection including tuberculosis, aberrant innominate artery, and pulmonary eosinophilia.17Chang A.B. Oppenheimer J.J. Weinberger M. Grant C.C. Rubin B.K. Irwin R.S. et al.Etiologies of chronic cough in pediatric cohorts: CHEST guideline and expert panel report.Chest. 2017; 152: 607-617Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar Clinical improvement after 2 weeks of antibiotics supports a diagnosis of clinical PBB. Effective empiric antibiotics obviate the need for referral to a subspecialty center and flexible bronchoscopy with lavage, hastening care and decreasing health care costs. In contrast, overdiagnosis of PBB and overuse of antibiotics have attendant negative impacts. PBB is often unrecognized, but has been found to be more common than asthma in some case series.10Chang A.B. Robertson C.F. Van Asperen P.P. Glasgow N.J. Mellis C.M. Masters I.B. et al.A multicenter study on chronic cough in children : burden and etiologies based on a standardized management pathway.Chest. 2012; 142: 943-950Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar PBB is more common in the setting of other conditions, notably airway malacia.18Kompare M. Weinberger M. Protracted bacterial bronchitis in young children: association with airway malacia.J Pediatr. 2012; 160: 88-92Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar PBB seems to be especially common in populations with high rates of respiratory infections associated with crowding and indoor air pollution, and in some indigenous populations.10Chang A.B. Robertson C.F. Van Asperen P.P. Glasgow N.J. Mellis C.M. Masters I.B. et al.A multicenter study on chronic cough in children : burden and etiologies based on a standardized management pathway.Chest. 2012; 142: 943-950Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar,19Laird P. Totterdell J. Walker R. Chang A.B. Schultz A. Prevalence of chronic wet cough and protracted bacterial bronchitis in aboriginal children.ERJ Open Res. 2019; 500248-2019Crossref PubMed Scopus (13) Google Scholar Failure to diagnose and treat PBB is associated with long-term impairment of lung function, suppurative lung disease, and bronchiectasis.20Wurzel D.F. Marchant J.M. Yerkovich S.T. Upham J.W. Petsky H.L. Smith-Vaughan H. et al.Protracted bacterial bronchitis in children: natural history and risk factors for bronchiectasis.Chest. 2016; 150: 1101-1108Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar The incidence of bronchiectasis is as high as 20 per 1000 children in some indigenous populations in high-income countries.21Singleton R. Morris A. Redding G. Poll J. Holck P. Martinez P. et al.Bronchiectasis in Alaska Native children: causes and clinical courses.Pediatr Pulmonol. 2000; 29: 182-187Crossref PubMed Scopus (216) Google Scholar Conversely, young children, especially those in daycare, commonly develop recurrent respiratory infections.22Schuez-Havupalo L. Toivonen L. Karppinen S. Kaljonen A. Peltola V. Daycare attendance and respiratory tract infections: a prospective birth cohort study.BMJ Open. 2017; 7e014635Crossref PubMed Scopus (40) Google Scholar,23Dales R.E. Cakmak S. Brand K. Judek S. Respiratory illness in children attending daycare.Pediatr Pulmonol. 2004; 38: 64-69Crossref PubMed Scopus (36) Google Scholar Each respiratory infection has the potential to cause a wet cough that lasts for 2-6 weeks; the child then can become infected with a new virus before resolution of the previous symptoms. This cycle can lead to a chronic cough that lasts for months. Concerns about antibiotic overuse include cost, effects on the microbiome, increased risk of developing obesity, Clostridioides difficile infection, and antibiotic resistance.24Ramirez J. Guarner F. Bustos Fernandez L. Maruy A. Sdepanian V.L. Cohen H. Antibiotics as major disruptors of gut microbiota.Front Cell Infect Microbiol. 2020; 10572912Crossref Scopus (273) Google Scholar, 25Sabtu N. Enoch D.A. Brown N.M. Antibiotic resistance: what, why, where, when and how?.Br Med Bull. 2015; 116: 105-113PubMed Google Scholar, 26Azad M.B. Owora A. Is early-life antibiotic exposure associated with obesity in children?.JAMA Netw Open. 2020; 3e1919694Crossref Scopus (2) Google Scholar, 27Meng X. Zhu Y. Di H. Zhang M. Feng J. Xu M. et al.Dose-response association of early-life antibiotic exposure and subsequent overweight or obesity in children: a meta-analysis of prospective studies.Obes Rev. 2021; 22e13321Crossref PubMed Scopus (8) Google Scholar Other concerns about antibiotics include hypersensitivity reactions or even more rare side effects, such as blood dyscrasias. One study noted that each additional day of antibiotics is associated with a 7% increase in odds of an adverse event.28Same R.G. Hsu A.J. Cosgrove S.E. Klein E.Y. Amoah J. Hersh A.L. et al.Antibiotic-associated adverse events in hospitalized children.J Pediatric Infect Dis Soc. 2021; 10: 622-628Crossref PubMed Scopus (14) Google Scholar This risk-benefit assessment has been calculated for the use of penicillin in cases of streptococcal pharyngitis to prevent rhematic heart disease.29McMurray K. Garber M. Taking chances with strep Throat.Hosp Pediatr. 2015; 5: 552-554Crossref PubMed Scopus (7) Google Scholar Antimicrobial stewardship programs seek to optimize antibiotic prescribing for infections, including antibiotic agent, dose, and duration for treatment, thereby decreasing the risk of promoting antimicrobial resistance or other adverse effects.30Donà D. Barbieri E. Daverio M. Lundin R. Giaquinto C. Zaoutis T. et al.Implementation and impact of pediatric antimicrobial stewardship programs: a systematic scoping review.Antimicrob Resist Infect Control. 2020; 9: 3Crossref PubMed Scopus (69) Google Scholar,31Zembles T.N. Nakra N. Parker S.K. Extending the reach of antimicrobial stewardship to pediatric patients.Infect Dis Ther. 2022; 11: 101-110Crossref PubMed Scopus (2) Google Scholar Empiric treatment of chronic wet cough per the guidelines leads to faster resolution of PBB, prevents long-term complications, and saves families financial and time burdens, as well as the risks of travel to a specialty center. However, following the guidelines in low-risk populations may lead to antibiotic overuse and serious complications. Adding to the uncertainty, the research supporting the use of antibiotics in chronic wet cough has not been evaluated in primary care settings in North America. Moreover, many antibiotics induce potent immunomodulatory responses, and it is uncertain to what extent these effects may impact the clinical course of chronic wet cough.32Tauber S.C. Nau R. Immunomodulatory properties of antibiotics.Curr Mol Pharmacol. 2008; 1: 68-79Crossref PubMed Google Scholar To identify the optimal treatment for chronic wet cough, prospective clinical trials of patients in North America are needed. In addition to controlled trials comparing outcomes of antibiotic- and placebo-treated groups, research is needed to differentiate more accurately children with recurrent viral respiratory infections from those with cough from other distinct etiologies. Cough frequency, duration, and qualitative features historically have relied on patient/family report. More objective measures of cough duration and characteristics would be useful to determine which patients to treat with antibiotics. Validated reports exist on cough and quality of life, but there is a lack of widely accepted cough sensors that could track children's cough.33Newcombe P.A. Sheffield J.K. Juniper E.F. Marchant J.M. Halsted R.A. Masters I.B. et al.Development of a parent-proxy quality-of-life chronic cough-specific questionnaire: clinical impact vs psychometric evaluations.Chest. 2008; 133: 386-395Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar,34Newcombe P.A. Sheffield J.K. Petsky H.L. Marchant J.M. Willis C. Chang A.B. A child chronic cough-specific quality of life measure: development and validation.Thorax. 2016; 71: 695-700Crossref PubMed Scopus (25) Google Scholar Multiple cough sensors currently are being evaluated but still are in early stages of development.35Rudd M. Song W.J. Small P.M. The statistics of counting coughs: easy as 1, 2, 3?.Lung. 2022; 200: 531-537Crossref PubMed Scopus (6) Google Scholar, 36Barata F. Cleres D. Tinschert P. Iris Shih C.H. Rassouli F. Boesch M. et al.Nighttime continuous contactless smartphone-based cough monitoring for the ward: validation study.JMIR Form Res. 2023; 7e38439Crossref PubMed Scopus (4) Google Scholar, 37Kruizinga M.D. Zhuparris A. Dessing E. Krol F.J. Sprij A.J. Doll R.J. et al.Development and technical validation of a smartphone-based pediatric cough detection algorithm.Pediatr Pulmonol. 2022; 57: 761-767Crossref PubMed Scopus (6) Google Scholar Development of technology capable of more reliably differentiating wet from dry cough would ensure that physicians are appropriately applying guidelines to patients. These sensors could potentially provide invaluable data differentiating the specific sound waves of coughs owing to PBB, gastroesophageal reflux, viral respiratory infections, and asthma. Future studies that identify noninvasive biomarkers (sputum or serum) for the diagnosis of PBB could guide care and reduce unnecessary antibiotic usage. We originally proposed a placebo-controlled research study within our National Institutes of Health-funded Environmental influences on Child Health Outcomes IDeA States Pediatric Trials Network. Our proposal was to treat children 6 months to 5 years of age with wet cough lasting more than 4 weeks with empiric antibiotics vs placebo. We proposed 2 weeks of amoxicillin-clavulanate vs placebo followed by 2 weeks of antibiotics for anyone still coughing as well as a 6-month follow up to determine recurrence rate between the groups. The reviewers within the network had strong opinions about the study, one way or the other. Some felt it was unethical to treat with antibiotics for potential viral illnesses. Some felt it was unethical not to treat with antibiotics given the risk of bronchiectasis. Given these strong opinions, the proposal did not move forward into a placebo-controlled trial. However, we believe that is exactly why this trial needs to be performed—to answer these questions better. The duration of antibiotics in PBB is another important question. Is 2 weeks necessary? Does 4 weeks decrease the recurrence rate? A better understanding of each individual host could guide these questions and aid in the determination of which child could benefit from a longer duration of antibiotics. In cystic fibrosis, a well-studied disease but with a completely different pathophysiology, there are no randomized controlled trials evaluating antibiotic duration.38Abbott L. Plummer A. Hoo Z.H. Wildman M. Duration of intravenous antibiotic therapy in people with cystic fibrosis.Cochrane Database Syst Rev. 2019; 9: CD006682PubMed Google Scholar In nonrandomized controlled studies, longer duration of antibiotics (13-15 days) is not superior to shorter duration (10-12 days), at least in terms of serum biomarkers of inflammation and lung function.39Nicholson T.T. Smith A. McKone E.F. Gallagher C.G. Duration of intravenous antibiotic treatment for acute exacerbations of cystic fibrosis: a systematic review.J Cyst Fibros. 2022; 21: 562-573Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Shorter courses of antibiotics for treatment of pneumonia recently have been demonstrated to be noninferior compared with longer courses.40Kuitunen I. Jääskeläinen J. Korppi M. Renko M. Antibiotic treatment duration for community acquired pneumonia in outpatient children in high-income countries - a systematic review and meta-analysis.Clin Infect Dis. 2023; 76: e1123-e1128Crossref PubMed Scopus (10) Google Scholar,41R Marques I. P Calvi I. A Cruz S. M F Sanchez L. F Baroni I. Oommen C. et al.Shorter versus longer duration of Amoxicillin-based treatment for pediatric patients with community-acquired pneumonia: a systematic review and meta-analysis.Eur J Pediatr. 2022; 181: 3795-3804Crossref PubMed Scopus (4) Google Scholar Because chronic cough is common, costly, and associated with decreased quality of life, multiple healthcare visits, and missed school, priority should be given to conducting trials that measure cough frequency and quality objectively as well as risk-benefit and cost-effectiveness of empiric antibiotic use for chronic wet cough.20Wurzel D.F. Marchant J.M. Yerkovich S.T. Upham J.W. Petsky H.L. Smith-Vaughan H. et al.Protracted bacterial bronchitis in children: natural history and risk factors for bronchiectasis.Chest. 2016; 150: 1101-1108Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar,42Prime S.J. Carter H.E. McPhail S.M. Petsky H.L. Chang A.B. Graves N. et al.Chronic wet cough in Australian children: societal costs and quality of life.Pediatr Pulmonol. 2021; 56: 2707-2716Crossref PubMed Scopus (6) Google Scholar,43Ruffles T.J.C. Marchant J.M. Masters I.B. Yerkovich S.T. Wurzel D.F. Gibson P.G. et al.Outcomes of protracted bacterial bronchitis in children: a 5-year prospective cohort study.Respirology. 2021; 26: 241-248Crossref PubMed Scopus (23) Google Scholar All authors are funded through the ECHO ISPCN NIH network. R.M. also receives funding from Merck for vaccine communication research. There are no real or perceived conflicts of interest in this commentary including the design, writing, or decision to submit.

Abstract Background Despite the disproportionate morbidity and mortality experienced by American Indian and Alaska Native (AI/AN) persons during the coronavirus disease 2019 (COVID-19) pandemic, few studies have reported vaccine effectiveness (VE) estimates among these communities. Methods We conducted a test-negative case-control analysis among AI/AN persons aged ≥12 years presenting for care from January 1, 2021, through November 30, 2021, to evaluate the effectiveness of mRNA COVID-19 vaccines against COVID-19-associated outpatient visits and hospitalizations. Cases and controls were patients with ≥1 symptom consistent with COVID-19-like illness; cases were defined as those test-positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and controls were defined as those test-negative for SARS-CoV-2. We used unconditional multivariable logistic regression to estimate VE, defined as 1 minus the adjusted odds ratio for vaccination among cases vs controls. Results The analysis included 207 cases and 267 test-negative controls. Forty-four percent of cases and 78% of controls received 2 doses of either BNT162b2 or mRNA-1273 vaccine. VE point estimates for 2 doses of mRNA vaccine were higher for hospitalized participants (94.6%; 95% CI, 88.0–97.6) than outpatient participants (86.5%; 95% CI, 63.0–95.0), but confidence intervals overlapped. Conclusions Among AI/AN persons, mRNA COVID-19 vaccines were highly effective in preventing COVID-associated outpatient visits and hospitalizations. Maintaining high vaccine coverage, including booster doses, will reduce the burden of disease in this population.

Respiratory syncytial virus (RSV) is the leading viral cause of acute lower respiratory tract infections, including bronchiolitis and pneumonia, in children under 5 years of age globally.1 Historically, RSV-associated hospitalization rates among American Indian and Alaska Native (AI/AN) children have been among the highest in the world.2-7 Contemporary estimates of RSV-acute respiratory infection (ARI) are needed to inform RSV prevention strategies for AI/AN children.

BACKGROUND:The COVID-19 pandemic is reported to have affected the epidemiology of respiratory syncytial virus (RSV), which could have important implications for RSV prevention and control strategies. We aimed to assess the hospitalisation burden of RSV-associated acute lower respiratory infection (ALRI) in children younger than 5 years during the pandemic period and the possible changes in RSV epidemiology from a global perspective. METHODS:We conducted a systematic literature search for studies published between Jan 1, 2020, and June 30, 2022, in MEDLINE, Embase, Global Health, Web of Science, the WHO COVID-19 Research Database, CINAHL, LILACS, OpenGrey, CNKI, WanFang, and CqVip. We included unpublished data on RSV epidemiology shared by international collaborators. Eligible studies reported data on at least one of the following measures for children (aged <5 years) hospitalised with RSV-associated ALRI: hospital admission rates, in-hospital case fatality ratio, and the proportion of hospitalised children requiring supplemental oxygen or requiring mechanical ventilation or admission to intensive care. We used a generalised linear mixed-effects model for data synthesis to measure the changes in the incidence, age distribution, and disease severity of children hospitalised with RSV-associated ALRI during the pandemic, compared with the year 2019. FINDINGS:We included 61 studies from 19 countries, of which 14 (23%) studies were from the published literature (4052 identified records) and 47 (77%) were from unpublished datasets. Most (51 [84%]) studies were from high-income countries; nine (15%) were from upper-middle-income countries, one (2%) was from a lower-middle-income country (Kenya), and none were from a low-income country. 15 studies contributed to the estimates of hospitalisation rate and 57 studies contributed to the severity analyses. Compared with 2019, the rates of RSV-associated ALRI hospitalisation in all children (aged 0-60 months) in 2020 decreased by 79·7% (325 000 cases vs 66 000 cases) in high-income countries, 13·8% (581 000 cases vs 501 000 cases) in upper-middle-income countries, and 42·3% (1 378 000 cases vs 795 000 cases) in Kenya. In high-income countries, annualised rates started to rise in 2021, and by March, 2022, had returned to a level similar to 2019 (6·0 cases per 1000 children [95% uncertainty interval 5·4-6·8] in April, 2021, to March, 2022, vs 5·0 cases per 1000 children [3·6-6·8] in 2019). By contrast, in middle-income countries, rates remained lower in the latest period with data available than in 2019 (for upper-middle-income countries, 2·1 cases [0·7-6·1] in April, 2021, to March, 2022, vs 3·4 [1·2-9·7] in 2019; for Kenya, 2·2 cases [1·8-2·7] in 2021 vs 4·1 [3·5-4·7] in 2019). Across all time periods and income regions, hospitalisation rates peaked in younger infants (aged 0 to <3 months) and decreased with increasing age. A significantly higher proportion of children aged 12-24 months were hospitalised with RSV-associated ALRI in high-income and upper-middle-income countries during the pandemic years than in 2019, with odds ratios ranging from 1·30 (95% uncertainty interval 1·07-1·59) to 2·05 (1·66-2·54). No consistent changes in disease severity were observed. INTERPRETATION:The hospitalisation burden of RSV-associated ALRI in children younger than 5 years was significantly reduced during the first year of the COVID-19 pandemic. The rebound in hospitalisation rates to pre-pandemic rates observed in the high-income region but not in the middle-income region by March, 2022, suggests a persistent negative impact of the pandemic on health-care systems and health-care access in the middle-income region. RSV surveillance needs to be established (or re-established) to monitor changes in RSV epidemiology, particularly in low-income and lower-middle-income countries. FUNDING:EU Innovative Medicines Initiative Preparing for RSV Immunisation and Surveillance in Europe (PROMISE), Bill & Melinda Gates Foundation, and WHO.

Background: In 2019, 5 cases of invasive Haemophilus influenzae serotype b (Hib) occurred in the Anchorage region of Alaska over a period of 16 days. No cases had occurred in Alaska in the preceding 26 months. Methods: Alaska Hib isolates from 2005 through 2019 were analyzed using whole-genome sequencing (WGS). Rates were compared with the CDC’s Active Bacterial Core surveillance (ABCs) data. Results: A total of 33 cases of invasive Hib occurred in Alaska from 2005 through 2019. Of the 5 cases associated with the cluster, 2 (40%) occurred in adults and all occurred in the Anchorage region. In contrast, only 14% (4/28) of the noncluster cases occurred in this region (P < 0.01). Two cluster cases were linked epidemiologically and the bacteria were nearly identical. The other 3 cluster cases were caused by 3 genetically distinct bacteria. When the full period was evaluated, the unadjusted rate of invasive Hib disease in Alaska was 15.5 times higher in Alaska Native (AN) people than non-AN people [1.3/100,000 vs. 0.07/100,000, 95% confidence intervals (CI): 10.2–22.5). The age-adjusted rate of invasive Hib disease in Alaska was 9.4 times higher than the ABCs rate (95% CI: 6.3–14.1). Conclusions: While clustered in time and space, the 5 cases in 2019 were not due to a single bacterial strain. AN people continue to have elevated rates of invasive Hib infection compared with both non-AN people in Alaska and the ABCs population.

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 (15100-49 100), 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. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

Objectives The number of women with opioid-related diagnoses in the United States has significantly increased in recent decades, resulting in concomitantly higher rates of infants born with neonatal opioid withdrawal syndrome (NOWS). Addressing prenatal opioid exposure is a priority for Alaska health systems. The objectives of this study were to: (1) identify maternal and neonatal factors associated with receipt of Medication for opioid use disorder (MOUD) and (2) determine the impact of prenatal MOUD on discharge to parents among infants with NOWS in 3 Alaska hospitals. Methods A retrospective chart review using a standard abstraction form was conducted to collect data on neonatal and maternal characteristics, neonatal treatment, and infant discharge disposition for infants with NOWS born at the 3 hospitals between July 2016 and December 2019. A multivariable logistic regression model was used to determine factors associated with discharge to parents. Results There were 10,719 births at the 3 hospitals during the study period, including 193 infants (1.8%) with NOWS. Among the 193 mothers, 91 (47.2%) received MOUD during pregnancy. Among infants with NOWS, 136 (70.5%) were discharged to parents, 51 (26.4%) were discharged to a relative or foster care. Infants were significantly (odds ratio 3.9) more likely to be discharged to parents if the mother had received prenatal MOUD. Conclusions MOUD among pregnant women with opioid use disorder furthers the goal of keeping families together and is a critical step towards reducing the impact of the ongoing opioid epidemic on Alaska families, communities, and the child welfare system.

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This paper presents estimates of the potential health-related economic benefits of providing universal access to in-home water and sanitation services to households in rural Alaska. In particular, we use data on disease incidence rates, health care costs, and local estimates of the impact of piped water on disease reduction to estimate the potential health-related economic benefits of providing universal access to piped water in the Yukon Kuskokwim (Y.K.) Delta region of Alaska. We include estimates of avoided treatment and diagnosis costs as well as private benefits associated with reduced morbidity and mortality associated with improved access to in-home piped water. To our knowledge, these are the first estimates of the economic benefits of improved access to water and sanitation in rural Alaska and the Arctic. Our analysis suggests increased access to in-home piped water in the region may yield substantial reductions in direct medical expenses incurred by public agencies and families, as well as reductions in time and travel costs associated with improved health outcomes. These benefits, along with the array of health and non-health-related benefits not included in our analysis, may provide new impetus to expanding access to high-quality water and sanitation services in the region.