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: Despite the disproportionate morbidity and mortality expeHealth Equity and Health Disparitiesrienced 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.

OBJECTIVES: In this study, we describe changes in LRTI rates from 1998-2014 among hospitalized AI/AN adults residing in Alaska and other Indian Health Service (IHS) regions. METHODS: We calculated age-adjusted hospital discharge rates and rate ratios from the IHS Direct and Contract Health Services Inpatient Dataset, IHS National Patient Information Reporting System for AI/AN adults ≥18 years, hospitalized at an IHS-operated, tribally operated or contract hospital with an LRTI-associated diagnosis during 1998-2014. RESULTS: Overall, there were 13,733 LRTI-associated hospitalizations in Alaska (1998-2014) with an age-adjusted rate of 13.7/1,000 adults. Among non-AK AI/AN, there were a total of 79,170 hospitalizations with a rate of 8.6/1,000 adults. In the pre-PCV7 and pre-PCV13 periods, LRTI rates were higher in AK AI/AN (12.4 and 14.1) compared to non-AK AI/AN (10.1 and 9.1, p<0.0001), respectively. In post-PCV7 and post-PCV13 periods, LRTI rates were also higher in AK (13.5 and 15.0) compared to non-AK (9.2 and 7.3, p<0.0001). CONCLUSIONS: Over the study period, we observed a 26% increase in rates of LRTI among adult AI/AN residing in Alaska compared with a 38% decrease in rates among AI/AN residing in non-AK. This disparity is likely due to a variety of factors such as tobacco use, crowding etc. Strategies to reduce LRTI in AI/AN adults are needed.

BACKGROUND: In Alaska, while introduction of 13-valent pneumococcal conjugate vaccine led to declines in invasive pneumococcal disease, carriage prevalence remained stable because of replacement with non-vaccine serotypes. We assessed antibiotic non-susceptibility of carried pneumococci during serotype redistribution, determined the contributions of within-serotype shifts, and assessed factors that could explain changes in non-susceptibility. METHODS: Each year from 2008 to 2015, at multiple sites in Alaska, we collected nasopharyngeal swabs and completed surveys for a convenience sample of participants. Pneumococcal serotyping and antimicrobial susceptibility testing for penicillin and erythromycin were performed. We described changes in non-susceptibility of isolates from 2008-2011 to 2012-2015, and assessed the contributions of serotype redistribution and within-serotype changes in non-susceptibility by comparing observed data to modeled data removing either factor. We used weighted logistic regression to assess whether reported risk factors could explain changes over time in non-susceptibility within serotypes. RESULTS: From 2008-2011 to 2012-2015, the overall proportion of isolates non-susceptible to penicillin or erythromycin increased by 3%, from 23% (n = 1,183) to 26% (n = 1,589; P < 0.05). However, a decrease of 3% would be expected if serotype redistribution occurred without within-serotype changes in non-susceptibility. Standardization by either factor produced hypothetical data significantly different to observed data. Within serotypes, the average annual increase in odds of non-susceptibility to penicillin or erythromycin was 1.08 (95% CI 1.05-1.11). Recent antibiotic exposure, urban residence and increased household size of participants predicted isolate non-susceptibility but did not explain the increase over time. DISCUSSION: An overall increase in non-susceptibility of carried pneumococcal isolates to penicillin or erythromycin resulted from increases in non-susceptibility within serotypes, which outweighed a protective effect of serotype redistribution. Characterization of emerging resistant clones within carried non-vaccine serotypes, including risk factors for colonization and disease, would support disease prevention efforts and inform vaccine strategies.

OBJECTIVE: The sole prospective longitudinal study of children with either chronic suppurative lung disease (CSLD) or bronchiectasis published in the current era was limited to a single center. We sought to extend this study by evaluating the longer-term clinical and lung function outcomes and their associated risk factors in Indigenous children of adolescents from Australia, Alaska, and New Zealand who participated in our previous CSLD or bronchiectasis studies during 2004-2010. METHODS: Between 2015 and 2018, we evaluated 131 out of 180 (72.8%) children of adolescents from the original studies at a single follow-up visit. We administered standardized questionnaires, reviewed medical records, undertook clinical examinations, performed spirometry, and scored available chest computed tomography scans. RESULTS: Participants were seen at a mean age of 12.3 years (standard deviation: 2.6) and a median of 9.0 years (range: 5.0-13.0) after their original recruitment. With increasing age, rates of acute lower respiratory infections (ALRI) declined, while lung function was mostly within population norms (median forced expiry volume in one-second = 90% predicted, interquartile range [IQR]: 81-105; forced vital capacity [FVC] = 98% predicted, IQR: 85-114). However, 43 out of 111 (38.7%) reported chronic cough episodes. Their overall global rating judged by symptoms, including ALRI frequency, examination findings, and spirometry was well (20.3%), stable (43.9%), or improved (35.8%). Multivariable regression identified household tobacco exposure and age at first ALRI-episode as independent risk factors associated with lower FVC% predicted values. CONCLUSION: Under our clinical care, the respiratory outcomes in late childhood or early adolescence are encouraging for these patient populations at high-risk of premature mortality. Prospective studies to further inform management throughout the life course into adulthood are now needed.

BACKGROUND: The lower respiratory tract infection (LRTI)-associated hospitalization rate in American Indian and Alaska Native (AI/AN) children aged <5 years declined during 1998-2008, yet remained 1.6 times higher than the general US child population in 2006-2008. PURPOSE: Describe the change in LRTI-associated hospitalization rates for AI/AN children and for the general US child population aged <5 years. METHODS: A retrospective analysis of hospitalizations with discharge ICD-9-CM codes for LRTI for AI/AN children and for the general US child population <5 years during 2009-2011 was conducted using Indian Health Service direct and contract care inpatient data and the Nationwide Inpatient Sample, respectively. We calculated hospitalization rates and made comparisons to previously published 1998-1999 rates prior to pneumococcal conjugate vaccine introduction. RESULTS: The average annual LRTI-associated hospitalization rate declined from 1998-1999 to 2009-2011 in AI/AN (35%, p<0.01) and the general US child population (19%, SE: 4.5%, p<0.01). The 2009-2011 AI/AN child average annual LRTI-associated hospitalization rate was 20.7 per 1,000, 1.5 times higher than the US child rate (13.7 95% CI: 12.6-14.8). The Alaska (38.9) and Southwest regions (27.3) had the highest rates. The disparity was greatest for infant (<1 year) pneumonia-associated and 2009-2010 H1N1 influenza-associated hospitalizations. CONCLUSIONS: Although the LRTI-associated hospitalization rate declined, the 2009-2011 AI/AN child rate remained higher than the US child rate, especially in the Alaska and Southwest regions. The residual disparity is likely multi-factorial and partly related to household crowding, indoor smoke exposure, lack of piped water and poverty. Implementation of interventions proven to reduce LRTI is needed among AI/AN children.

BACKGROUND: Acute respiratory exacerbations (AREs) cause morbidity and lung function decline in children with chronic suppurative lung disease (CSLD) and bronchiectasis. In a prospective longitudinal cohort study, we determined the patterns of AREs and factors related to increased risks for AREs in children with CSLD/bronchiectasis. METHODS: Ninety-three indigenous children aged 0.5 to 8 years with CSLD/bronchiectasis in Australia (n = 57) and Alaska (n = 36) during 2004 to 2009 were followed for > 3 years. Standardized parent interviews, physical examinations, and medical record reviews were undertaken at enrollment and every 3 to 6 months thereafter. RESULTS: Ninety-three children experienced 280 AREs (median = 2, range = 0-11 per child) during the 3-year period; 91 (32%) were associated with pneumonia, and 43 (15%) resulted in hospitalization. Of the 93 children, 69 (74%) experienced more than two AREs over the 3-year period, and 28 (30%) had more than one ARE in each study year. The frequency of AREs declined significantly over each year of follow-up. Factors associated with recurrent (two or more) AREs included age < 3 years, ARE-related hospitalization in the first year of life, and pneumonia or hospitalization for ARE in the year preceding enrollment. Factors associated with hospitalizations for AREs in the first year of study included age < 3 years, female caregiver education, and regular use of bronchodilators. CONCLUSIONS: AREs are common in children with CSLD/bronchiectasis, but with clinical care and time AREs occur less frequently. All children with CSLD/bronchiectasis require comprehensive care; however, treatment strategies may differ for these patients based on their changing risks for AREs during each year of care.

BACKGROUND: Alaska Native infants experience high rates of respiratory syncytial virus (RSV) hospitalizations. Through 2008, Alaska administered a 7-dose (maximum) palivizumab regime to high-risk infants from October to May. In 2009, the maximum was reduced to 3 doses for 32- to 34-week preterm babies and 6 doses for other groups. METHODS: We used 11 years of data and regional Medicaid reimbursement rates to model the cost effectiveness of 4 palivizumab intervention strategies to reduce RSV hospitalizations among Alaskan infants including: current strategy, old strategy (1998-2008), and 2 hypothetical strategies using the current strategy plus 1 or 3 doses to all newborn infants during the RSV season. RESULTS: The current strategy represents 5 hospitalizations averted per year for the palivizumab cohort (~50-56 children) at ~$52 846 per hospitalization averted, compared with no intervention. Compared with the old strategy, the mean cost per hospitalization prevented for the current strategy was 63% lower, net program costs were 85% lower, and the mean hospitalizations prevented were 27% lower. Compared with current strategy only, the addition of 1 dose to all newborns during the RSV season could decrease the mean cost per hospitalization prevented by 23%, increase the number of hospitalizations prevented by 2.5-fold, and increase the net programmatic costs by 3.3-fold; administering up to 3 doses to infants further reduced hospitalizations and increased costs. CONCLUSIONS: The current palivizumab strategy improved the cost-effectiveness ratio compared with the old strategy. Further improvement could be obtained by adding doses for Alaskan Native newborns during the RSV season; however, programmatic costs would increase.

BACKGROUND: In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced a 7-valent vaccine (PCV7) that contained all PCV7 serotypes plus 6 additional serotypes (PCV6+). We conducted annual surveys from 2008 to 2012 to determine the effect of PCV13 on colonization by pneumococcal serotypes. METHODS: We obtained nasopharyngeal swabs for pneumococcal identification and serotyping from residents of all ages at 8 rural villages and children age <60 months at 2 urban clinics. We conducted interviews/medical records review for all participants. RESULTS: A total of 18 207 nasopharyngeal swabs (rural = 16 098; urban = 2109) were collected. From 2008 to 2012, 84% of rural and 90% of urban children age <5 years were age-appropriately vaccinated with a PCV. Overall pneumococcal colonization prevalence remained stable among rural (66%) and urban (35%) children age <5 years, and adults age ≥18 years (14%). Colonization by PCV6+ serotypes declined significantly among rural children age <5 years, urban children age <5, and adults age ≥18 over the course of the study (25%-5%, 22%-9%, 22%-6%, respectively). CONCLUSIONS: PCV13 was rapidly introduced into the Alaska childhood immunization schedule and reduced colonization by PCV6+ serotypes among children. Unvaccinated adults also experienced comparable reductions in vaccine serotype colonization indicating substantial indirect protection from PCV13.

OBJECTIVES: We described American Indian/Alaska Native (AI/AN) infant and pediatric death rates and leading causes of death. METHODS: We adjusted National Vital Statistics System mortality data for AI/AN racial misclassification by linkage with Indian Health Service (IHS) registration records. We determined average annual death rates and leading causes of death for 1999 to 2009 for AI/AN versus White infants and children. We limited the analysis to IHS Contract Health Service Delivery Area counties. RESULTS: The AI/AN infant death rate was 914 (rate ratio [RR] = 1.61; 95% confidence interval [CI] = 1.55, 1.67). Sudden infant death syndrome, unintentional injuries, and influenza or pneumonia were more common in AI/AN versus White infants. The overall AI/AN pediatric death rates were 69.6 for ages 1 to 4 years (RR = 2.56; 95% CI = 2.38, 2.75), 28.9 for ages 5 to 9 years (RR = 2.12; 95% CI = 1.92, 2.34), 37.3 for ages 10 to 14 years (RR = 2.22; 95% CI = 2.04, 2.40), and 158.4 for ages 15 to 19 years (RR = 2.71; 95% CI = 2.60, 2.82). Unintentional injuries and suicide occurred at higher rates among AI/AN youths versus White youths. CONCLUSIONS: Death rates for AI/AN infants and children were higher than for Whites, with regional disparities. Several leading causes of death in the AI/AN pediatric population are potentially preventable.

OBJECTIVES: We compared pneumonia and influenza death rates among American Indian/Alaska Native (AI/AN) people with rates among Whites and examined geographic differences in pneumonia and influenza death rates for AI/AN persons. METHODS: We adjusted National Vital Statistics Surveillance mortality data for racial misclassification of AI/AN people through linkages with Indian Health Service (IHS) registration records. Pneumonia and influenza deaths were defined as those who died from 1990 through 1998 and 1999 through 2009 according to codes for pneumonia and influenza from the International Classification of Diseases, 9th and 10th Revision, respectively. We limited the analysis to IHS Contract Health Service Delivery Area counties, and compared pneumonia and influenza death rates between AI/ANs and Whites by calculating rate ratios for the 2 periods. RESULTS: Compared with Whites, the pneumonia and influenza death rate for AI/AN persons in both periods was significantly higher. AI/AN populations in the Alaska, Northern Plains, and Southwest regions had rates more than 2 times higher than those of Whites. The pneumonia and influenza death rate for AI/AN populations decreased from 39.6 in 1999 to 2003 to 33.9 in 2004 to 2009. CONCLUSIONS: Although progress has been made in reducing pneumonia and influenza mortality, disparities between AI/AN persons and Whites persist. Strategies to improve vaccination coverage and address risk factors that contribute to pneumonia and influenza mortality are needed.

BACKGROUND: Routine childhood varicella vaccination, implemented in 1995, has resulted in significant declines in varicella-related hospitalizations in the United States. Varicella hospitalization rates among the American Indian and Alaska Native (AI/AN) population have not been previously documented. METHODS: We selected varicella-related hospitalizations, based on a published definition, from the Indian Health Service inpatient database for AI/ANs in the Alaska, Southwest and Northern Plains regions (1995-2010) and from the Nationwide Inpatient Sample for the general US population (2007-2010). We analyzed average annual hospitalization rates pre-vaccine (1995-1998) and post-vaccine (2007-2010) for the AI/AN population, and post-vaccine for the general US population. RESULTS: From 1995-1998 to 2007-2010, the average annual varicella-related hospitalization rate for AI/ANs in the three regions decreased 95% (0.66 to 0.03/10,000 persons); the post-vaccine rate appears lower than the general US rate (0.06, 95% CI 0.05-0.06). The rate declined in all AI/AN pediatric age groups. Infants experienced the highest pre-vaccine (14.07) and post-vaccine (0.83) hospitalization rates. Adults experienced low rates in both time periods. Varicella vaccination rates in 19-35 month old AI/AN children during fiscal years 2008-2010 were 88.1% to 91.0%. CONCLUSIONS: Widespread use of varicella vaccine in AI/AN children was accompanied by substantial declines in varicella-related hospitalizations consistent with high varicella vaccine effectiveness in preventing severe varicella outcomes.

BACKGROUND: Indigenous children in Australia and Alaska have very high rates of chronic suppurative lung disease (CSLD)/bronchiectasis. Antibiotics, including frequent or long-term azithromycin in Australia and short-term beta-lactam therapy in both countries, are often prescribed to treat these patients. In the Bronchiectasis Observational Study we examined over several years the nasopharyngeal carriage and antibiotic resistance of respiratory bacteria in these two PCV7-vaccinated populations. METHODS: Indigenous children aged 0.5-8.9 years with CSLD/bronchiectasis from remote Australia (n = 79) and Alaska (n = 41) were enrolled in a prospective cohort study during 2004-8. At scheduled study visits until 2010 antibiotic use in the preceding 2-weeks was recorded and nasopharyngeal swabs collected for culture and antimicrobial susceptibility testing. Analysis of respiratory bacterial carriage and antibiotic resistance was by baseline and final swabs, and total swabs by year. RESULTS: Streptococcus pneumoniae carriage changed little over time. In contrast, carriage of Haemophilus influenzae declined and Staphylococcus aureus increased (from 0% in 2005-6 to 23% in 2010 in Alaskan children); these changes were associated with increasing age. Moraxella catarrhalis carriage declined significantly in Australian, but not Alaskan, children (from 64% in 2004-6 to 11% in 2010). While beta-lactam antibiotic use was similar in the two cohorts, Australian children received more azithromycin. Macrolide resistance was significantly higher in Australian compared to Alaskan children, while H. influenzae beta-lactam resistance was higher in Alaskan children. Azithromycin use coincided significantly with reduced carriage of S. pneumoniae, H. influenzae and M. catarrhalis, but increased carriage of S. aureus and macrolide-resistant strains of S. pneumoniae and S. aureus (proportion of carriers and all swabs), in a 'cumulative dose-response' relationship. CONCLUSIONS: Over time, similar (possibly age-related) changes in nasopharyngeal bacterial carriage were observed in Australian and Alaskan children with CSLD/bronchiectasis. However, there were also significant frequency-dependent differences in carriage and antibiotic resistance that coincided with azithromycin use.

BACKGROUND: The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown. We aimed to estimate the incidence of admissions and deaths for such infections in children younger than 5 years in 2010. METHODS: We estimated the incidence of admissions for severe and very severe ALRI in children younger than 5 years, stratified by age and region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies. We applied these incidence estimates to population estimates for 2010, to calculate the global and regional burden in children admitted with severe ALRI in that year. We estimated in-hospital mortality due to severe and very severe ALRI by combining incidence estimates with case fatality ratios from hospital-based studies. FINDINGS: We identified 89 eligible studies and estimated that in 2010, 11.9 million (95% CI 10.3-13.9 million) episodes of severe and 3.0 million (2.1-4.2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide. Incidence was higher in boys than in girls, the sex disparity being greatest in South Asian studies. On the basis of data from 37 hospital studies reporting case fatality ratios for severe ALRI, we estimated that roughly 265,000 (95% CI 160,000-450,000) in-hospital deaths took place in young children, with 99% of these deaths in developing countries. Therefore, the data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals. INTERPRETATION: Severe ALRI is a substantial burden on health services worldwide and a major cause of hospital referral and admission in young children. Improved hospital access and reduced inequities, such as those related to sex and rural status, could substantially decrease mortality related to such infection. Community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities. FUNDING: WHO.

OBJECTIVE: Indigenous children in developed countries are at increased risk of chronic suppurative lung disease (CSLD), including bronchiectasis. We evaluated sociodemographic and medical factors in indigenous children with CSLD/bronchiectasis from Australia, United States (US), and New Zealand (NZ). METHODS: Indigenous children aged 0.5-8 years with CSLD/bronchiectasis were enrolled from specialist clinics in Australia (n = 97), Alaska (n = 41), and NZ (n = 42) during 2004-2009, and followed for 1-5 years. Research staff administered standardized parent interviews, reviewed medical histories and performed physical examinations at enrollment. RESULTS: Study children in all three countries had poor housing and sociodemographic circumstances at enrollment. Except for increased household crowding, most poverty indices in study participants were similar to those reported for their respective local indigenous populations. However, compared to their local indigenous populations, study children were more often born prematurely and had both an increased frequency and earlier onset of acute lower respiratory infections (ALRIs). Most (95%) study participants had prior ALRI hospitalizations and 77% reported a chronic cough in the past year. Significant differences (wheeze, ear disease and plumbed water) between countries were present. DISCUSSION: Indigenous children with CSLD/bronchiectasis from three developed countries experience significant disparities in poverty indices in common with their respective indigenous population; however, household crowding, prematurity and early ALRIs were more common in study children than their local indigenous population. Addressing equity, especially by preventing prematurity and ALRIs, should reduce risk of CSLD/bronchiectasis in indigenous children. (Pediatr Pulmonol. (c) 2013 Wiley Periodicals, Inc.)

Outbreaks of invasive pneumococcal disease (IPD) caused by serotype 12F Streptococcus pneumoniae were observed in two neighboring regions of rural Alaska in 2003-2006 and 2006-2008. IPD surveillance data from 1986-2009 and carriage survey data from 1998-2004 and 2008-2009 were reviewed to identify patterns of 12F transmission. Pulsed field gel electrophoresis was performed on all available isolates, and selected isolates were characterized by additional genetic subtyping methods. Serotype 12F IPD occurred in two waves in Alaska between 1986 and 2008. While cases of disease occurred nearly every year in Anchorage, in rural regions 12F IPD occurred with rates 10 to 20-fold higher than in Anchorage, often with many years between disease peaks, and generally caused by a single predominant genetic clone. Carriage occurred predominantly in adults, except early in rural outbreaks when most carriage was in persons <18 years old. In rural regions, carriage of 12F disappeared completely after outbreaks. Different 12F clones appear to have been introduced episodically into rural populations, spread widely in young, immunologically naive populations, leading to outbreaks of IPD lasting 1-3 years, then rapidly disappeared from the population. Larger population centers may have been the reservoir for these clones. This epidemiologic pattern is consistent with a highly virulent, but immunogenic, form of pneumococcus.

OBJECTIVE: Beginning in 2006, the Indian Health Service (IHS) began rotavirus vaccination of American Indian and Alaska Native (AI/AN) infants. To assess vaccine impact, we examined trends in IHS diarrhea-associated hospitalization and outpatient visits among AI/AN children in the pre- and postrotavirus vaccine era. METHODS: Diarrhea-associated hospitalizations and outpatient visits among AI/AN children <5 years of age during 2001 through 2010 were examined by gender, age group, and region for prevaccine years 2001-2006 and postvaccine years 2008, 2009, and 2010. To account for secular declining trends observed in prevaccine years, expected diarrhea-associated hospitalization and outpatient rates for postvaccine years were generated by using Poisson regression analysis of the 2001-2006 annual rates. RESULTS: Coverage with at least 1 dose of rotavirus vaccine among AI/AN infants aged 3 to 5 months in the first half of 2008, 2009, and 2010 ranged from 48% to 80% in various IHS regions. The prevaccine average annual diarrhea-associated hospitalization rates among AI/AN children <5 years of age was 63 per 10,000 persons (range: 57-75 per 10,000), and declined to 39, 31, and 27 per 10,000 in 2008, 2009, and 2010, respectively. Observed 2008, 2009, and 2010 rates were 24%, 37%, and 44% lower than expected rates, respectively. Decreases in diarrhea-associated hospitalizations and outpatient visits were observed in all IHS regions. CONCLUSIONS: Diarrhea-associated hospitalization and outpatient visit rates among AI/AN children have declined after implementation of rotavirus vaccination in AI/AN populations.

OBJECTIVE: Lower respiratory tract infections (LRTIs) are a major cause of morbidity for children worldwide and particularly for children from developing and indigenous populations. In this study, we evaluated risk factors for hospitalization with LRTI in a region in southwest Alaska. METHODS: The study was conducted from October 1, 2006, to September 30, 2007, in the Yukon Kuskokwim Delta region of Alaska. Cases were recruited from children <3 years of age hospitalized with LRTI. Controls were recruited during visits to the surrounding communities in the region and matched posthoc to cases on the basis of subregion, season, and age. Parents were interviewed for potential risk factors, and medical records were reviewed. Participants had a nasopharyngeal swab sample taken for polymerase chain reaction (PCR) testing for a panel of respiratory viruses. Samples positive for respiratory syncytial virus, human metapneumovirus, or parainfluenza type 3 were quantitated by reverse transcriptase real-time quantitative PCR. RESULTS: One hundred twenty-eight cases were matched to 186 controls. In a multivariable conditional logistic regression model, significantly (P < .05) increased risk of hospitalization was associated with medically high-risk status, having a woodstove in the house, being bottle fed, and vomiting after feeding; living in a house that had 2 or more rooms with sinks was a protective factor. Viral loads in hospitalized cases were significantly higher than those in controls, but a strict cutoff level was not observed. CONCLUSIONS: Several risk factors for LRTI hospitalization were identified in this high risk population. Some factors are amenable to environmental and behavioral interventions.

OBJECTIVE: To describe trends in the rate of hospitalization for lower respiratory tract infection (LRTI) among American Indian/Alaska Native (AI/AN) children and the general US population of children aged <5 years. STUDY DESIGN: This was a retrospective analysis of trends and hospitalization rates for LRTI-associated hospitalizations in 1998-2008 among AI/AN children aged <5 years using the Indian Health Service direct/contract inpatient data, and also among the general population of US children aged <5 years using the Nationwide Inpatient Sample. RESULTS: The 2006-2008 LRTI-associated hospitalization rate for AI/AN children aged <5 years (21.8 per 1000/year) was 32% lower than the 1998-1999 rate, and 1.6-fold higher than the general US children rate (13.8 per 1000/year; 95% CI, 12.8-14.8). Higher rates were seen in AI/AN children aged <5 years in the Alaska and the Southwest regions of the United States (41.2 and 28.0 per 1000/year, respectively). In infants, these rates were 136.4 and 82.4 per 1000/year, respectively, exceeding the rate in the general US infant population (37.1 per 1000/year; 95% CI, 34.3-40.0). The greatest disparity in the LRTI-associated hospitalization rate between AI/AN infants and the general US infant population was seen for pneumonia, with a 3-fold higher rate in AI/AN infants (36.2 per 1000/year vs 12.7 per 1000/year; 95% CI, 11.8-13.6). CONCLUSION: The LRTI-associated hospitalization rate is higher in AI/AN children, particularly infants from Alaska and the American Southwest, compared with the general US child population. Closing this gap will require addressing housing and sanitation inequities and ensuring high immunization rates and access to care.

OBJECTIVES: We described disparities in infectious disease (ID) hospitalizations for American Indian/Alaska Native (AI/AN) people. METHODS: We analyzed hospitalizations with an ID listed as the first discharge diagnosis in 1998-2006 for AI/AN people from the Indian Health Service National Patient Information Reporting System and compared them with records for the general U.S. population from the Nationwide Inpatient Survey. RESULTS: The ID hospitalization rate for AI/AN people declined during the study period. The 2004-2006 mean annual age-adjusted ID hospitalization rate for AI/AN people (1,708 per 100,000 populiation) was slightly higher than that for the U.S. population (1,610 per 100,000 population). The rate for AI/AN people was highest in the Southwest (2,314 per 100,000 population), Alaska (2,063 per 100,000 population), and Northern Plains West (1,957 per 100,000 population) regions, and among infants (9,315 per 100,000 population). ID hospitalizations accounted for approximately 22% of all AI/AN hospitalizations. Lower-respiratory-tract infections accounted for the largest proportion of ID hospitalizations among AI/AN people (35%) followed by skin and soft tissue infections (19%), and infections of the kidney, urinary tract, and bladder (11%). CONCLUSIONS: Although the ID hospitalization rate for AI/AN people has declined, it remains higher than that for the U.S. general population, and is highest in the Southwest, Northern Plains West, and Alaska regions. Lower-respiratory-tract infections; skin and soft tissue infections; and kidney, urinary tract, and bladder infections contributed most to these health disparities. Future prevention strategies should focus on high-risk regions and age groups, along with illnesses contributing to health disparities.

Alaska Native people experienced the highest rates of acute and chronic hepatitis B virus (HBV) infection, and hepatocellular carcinoma (HCC) in the United States. We examine the effect of a universal newborn immunization with hepatitis B vaccine and mass population screening immunization program initiated in 1984 on rates of HBV and HCC in children 25 years later. During this time period, the population of Alaska Native people grew from an estimated 75,000 to 130,000 persons. A surveillance system to detect acute HBV infection in Alaska Native facilities was established in 1981. Cases of HCC in children under 20 years of age were identified using a National Cancer Institute (NCI) funded Cancer Registry established in 1969 coupled with an active surveillance program of screening persons with chronic HBV semiannually for alpha-fetoprotein since 1982. The incidence of acute symptomatic HBV infection in persons < 20 years of age fell from cases 19/100,000 in 1981-1982 to 0/100,000 in 1993-94, respectively. No cases of acute HBV have occurred in children since 1992. The incidence of HCC in persons < 20 years decreased from 3/100,000 in 1984-1988 to zero in 1995-1999 and no cases have occurred since 1999. The number of identified HBsAg-positive children < 20 years in the Alaska Native Population declined from 657 in 1987 to two in 2008. Universal newborn vaccination coupled with mass screening and immunization of susceptible Alaska Native has eliminated HCC and acute symptomatic HBV infection among Alaska Native children and this approach is the best way to prevent HBV related disease in children. (HEPATOLOGY 2011.).

BACKGROUND: Older adults are at highest risk of invasive pneumococcal disease (IPD) and are recommended to receive vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23). Antibody concentrations decline following vaccination. We evaluated the immunogenicity and reactogenicity of revaccination and repeat revaccination. METHODS: Adults aged 55-74 years were vaccinated with a 1st to 4th dose of PPV23. Participants were eligible for revaccination if a minimum of 6 years had passed since their last dose of PPV23. Blood collected on the day of vaccination and 30 days later was analyzed by ELISA for IgG to five serotypes. Functional antibody activity was measured using an opsonophagocytic killing (OPK) assay. Reactions to vaccination were documented. RESULTS: Subjects were vaccinated with a 1st dose (n=123), 2nd dose (n=121), or 3rd or 4th dose (n=71) of PPV23. The post-vaccination IgG geometric mean concentrations (GMCs) were similar among first-time vaccinees and re-vaccinees for all serotypes with the exception of a lower GMC for serotype 1 in re-vaccinees. The post-vaccination OPK geometric mean titers (GMTs) were similar among first-time vaccinees and re-vaccinees with the exception of a higher GMT for serotype 6B in re-vaccinees. Compared to first-time vaccinees, re-vaccinees reported more joint pain (p=0.003), fatigue (p=0.027), headache (p=0.011), swelling (p=0.009), and moderate limitation in arm movement (p=0.015). CONCLUSIONS: Repeat revaccination with PPV23, administered 6 or more years after the prior dose, was immunogenic and generally well tolerated.

We analyzed hospitalizations for empyema among Alaska Native (AN) children and the general population of US children <10 years during the years 1998 to 2007. We also analyzed invasive pneumococcal disease in AN children. Between 1998 and 2000, the average annual hospitalization rate for empyema was higher for AN children (51.8 per 100,000/yr) than that for US children (24.2 [95% confidence interval: 20.4, 27.9] per 100,000/yr), and had increased in 2004-2007 in both populations (59.6 and 36.0 [95% confidence interval: 30.1, 41.8], respectively). Pneumococcal empyema increased in AN children despite a decrease in invasive pneumococcal disease pneumonia.

Historically, Alaska experienced cyclic hepatitis A virus (HAV) epidemics, and the HAV rate among Alaska Native people was significantly higher than among other racial/ethnic groups. We evaluated the impact of universal childhood vaccination, initiated in 1996, on HAV epidemiology in Alaska by analyzing HAV cases reported to the State of Alaska. HAV incidence in all age groups declined 98.6% from 60.0/100,000 in 1972-1995 to 0.9/100,000 in 2002-2007. The largest decrease (99.9%) was in Alaska Native people, whose incidence (0.3) in 2002-2007 was lower than the overall US 2007 rate (1.0). Among age groups, the decrease (99.8%) among children aged 0-14 years was the largest. Routine childhood vaccination has nearly eliminated HAV infection in Alaska.

Respiratory syncytial virus (RSV) in Alaska Native children from the Yukon Kuskokwim (YK) Delta is associated with a hospitalization rate five times higher than that reported for the general US child population. The role of other viral respiratory pathogens has not been studied in this population. YK Delta children <3 years of age hospitalized with respiratory infections and same aged community control children were prospectively enrolled between October 2005 and September 2007. Polymerase chain reaction detection of viruses was performed on nasopharyngeal samples. Characteristics of hospitalized and asymptomatic control children were analyzed. From October 2005 to September 2007, 440 hospitalized and 425 control children were analyzed. Respiratory viruses were detected in 90% (395) of hospitalized children: 194 (44%) rhinovirus, 131 (30%) adenovirus, 102 (23%) RSV, 77 (18%) para influenza viruses (PIV), 66 (15%) human metapneumovirus (hMPV), 23 (5%) influenza, and 25 (6%) coronavirus. Fifty-two percent (221) of control children had a virus detected, most commonly rhinovirus (33%), and adenovirus (16%). RSV, PIV, hMPV, and influenza were significantly more common in hospitalized cases than control children, but rhinovirus, adenovirus, and coronavirus were not. RSV and hMPV were associated with higher severity of illness. In this study, RSV remains the most important virus associated with respiratory hospitalization, although hMPV and PIV were also common. RSV and hMPV were associated with more severe illness. Rhinovirus and adenovirus were detected in two-thirds of hospitalized children, but their frequent detection in control children made their role in respiratory hospitalization uncertain.

There are many similarities regarding the health status of Indigenous people in the 4 English-speaking developed countries of North America and the Pacific (United States, Canada, Australia, New Zealand), where they are all now minority populations. Although vaccines have contributed to the reduction or elimination of disease disparities for many infections, Indigenous people continue to have higher morbidity and mortality from many chronic and infectious diseases compared with the general populations in their countries. This review summarizes the available data on the epidemiology of vaccine-preventable diseases in Indigenous populations in these 4 countries in the context of the vaccination strategies used and their impact, with the aim of identifying successful strategies with the potential for wider implementation.

OBJECTIVE: To describe maternal and birth-related risk factors associated with lower respiratory tract infection (LRTI) deaths among infants. METHODS: Records for infants with LRTI as a cause of death were examined by using the linked birth/infant death database for 1999-2004. Singleton infants dying with LRTI and a random sample of surviving singleton infants were compared for selected characteristics. RESULTS: A total of 5420 LRTI-associated infant deaths were documented in the United States during 1999-2004, for an LRTI-associated infant mortality rate of 22.3 per 100,000 live births. Rates varied according to race; the rate for American Indian/Alaska Native (AI/AN) infants was highest (53.2), followed by black (44.1), white (18.7), and Asian/Pacific Islander infants (12.3). Singleton infants with low birth weight (<2500 g) were at increased risk of dying with LRTI after controlling for other characteristics, especially black infants. Both AI/AN and black infants born with a birth weight of > or =2500 g were more likely to have died with LRTI than other infants of the same birth weight. Other risk factors associated with LRTI infant death included male gender, the third or more live birth, an Apgar score of <8, unmarried mother, mother with <12 years of education, mother <25 years of age, and mother using tobacco during pregnancy. CONCLUSIONS: Low birth weight was associated with markedly increased risk for LRTI-associated death among all of the racial groups. Among infants with a birth weight of > or =2500 g, AI/AN and black infants were at higher risk of LRTI-associated death, even after controlling for maternal and birth-related factors. Additional studies and strategies should focus on the prevention of maternal and birth-related risk factors for postneonatal LRTI and on identifying additional risk factors that contribute to elevated mortality among AI/AN and black infants.

BACKGROUND: Vaccination with conjugate vaccines stimulates T cell-dependent immunity, whereas vaccination with polysaccharide vaccines does not. Thus, vaccination with the 7-valent pneumococcal conjugate vaccine (PCV7) followed by the 23-valent pneumococcal polysaccharide vaccine (PPV23) may offer better protection against invasive pneumococcal disease for older adults than does vaccination with PPV23 alone, which is what is currently recommended. METHODS: Alaska Native adults 55-70 years of age with no previous pneumococcal vaccination were randomized to receive (1) PPV23, (2) PCV7 followed 2 months later by PPV23, or (3) PCV7 followed 6 months later by PPV23. Participants recorded reactions after each vaccination. Serum samples collected during the period from May 2002 through February 2003 were tested for serotype-specific immunoglobulin G (IgG) and for opsonophagocytic activity (OPA) against serotypes 1, 4, 6B, 14, and 19F. RESULTS: Vaccination with PCV7 was well tolerated, but persons receiving PCV7 followed by PPV23 reported more local reactions than those receiving only PPV23. All reactions resolved spontaneously within 72 h of receiving vaccine. The geometric mean IgG concentrations of and the median OPA titers to serotypes 4, 6B, 14, and 19F increased in all groups after 1 dose of either PCV7 or PPV23. Serotype-specific geometric mean IgG concentrations and median OPA titers did not differ between any of the groups after vaccination with PPV23, regardless of whether they had previously received PCV7. CONCLUSIONS: In this study, PCV7 given 2 or 6 months before PPV23 was well tolerated but did not improve immune response to PPV23 in older Alaska Native adults.