OBJECTIVE: Our objectives with this study were to describe the frequency of selected cooccurring health conditions and individualized education program (IEP) services and post-high school transition planning for adolescents with autism spectrum disorder and identify disparities by sex, intellectual ability, race or ethnicity, and geographic area. METHODS: The study sample included 1787 adolescents born in 2004 who were identified as having autism through a health and education record review through age 16 years in 2020. These adolescents were part of a longitudinal population-based surveillance birth cohort from the Autism and Developmental Disabilities Monitoring Network from 2004 to 2020 in 5 US catchment areas. RESULTS: Attention deficit hyperactivity disorder (47%) and anxiety (39%) were the most common cooccurring health conditions. Anxiety was less commonly identified for those with intellectual disability than those without. It was also less commonly identified among Black adolescents compared with White or Hispanic adolescents. There was wide variation across Autism and Developmental Disabilities Monitoring Network sites in the provision of school-based IEP services. Students with intellectual disability were less likely to receive school-based mental health services and more likely to have a goal for postsecondary independent living skills compared with those without intellectual disability. A total of 37% of students did not participate in standardized testing. CONCLUSIONS: We identified disparities in the identification of cooccurring conditions and school-based IEP services, practices, and transition planning. Working with pediatric health and education providers, families, and adolescents with autism will be important to identify contributing factors and to focus efforts to reduce disparities in the supports and services adolescents with autism have access to and receive.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2020. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years. In 2020, there were 11 ADDM Network sites across the United States (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin). To ascertain ASD among children aged 8 years, ADDM Network staff review and abstract developmental evaluations and records from community medical and educational service providers. A child met the case definition if their record documented 1) an ASD diagnostic statement in an evaluation, 2) a classification of ASD in special education, or 3) an ASD International Classification of Diseases (ICD) code. RESULTS: For 2020, across all 11 ADDM sites, ASD prevalence per 1,000 children aged 8 years ranged from 23.1 in Maryland to 44.9 in California. The overall ASD prevalence was 27.6 per 1,000 (one in 36) children aged 8 years and was 3.8 times as prevalent among boys as among girls (43.0 versus 11.4). Overall, ASD prevalence was lower among non-Hispanic White children (24.3) and children of two or more races (22.9) than among non-Hispanic Black or African American (Black), Hispanic, and non-Hispanic Asian or Pacific Islander (A/PI) children (29.3, 31.6, and 33.4 respectively). ASD prevalence among non-Hispanic American Indian or Alaska Native (AI/AN) children (26.5) was similar to that of other racial and ethnic groups. ASD prevalence was associated with lower household income at three sites, with no association at the other sites.Across sites, the ASD prevalence per 1,000 children aged 8 years based exclusively on documented ASD diagnostic statements was 20.6 (range = 17.1 in Wisconsin to 35.4 in California). Of the 6,245 children who met the ASD case definition, 74.7% had a documented diagnostic statement of ASD, 65.2% had a documented ASD special education classification, 71.6% had a documented ASD ICD code, and 37.4% had all three types of ASD indicators. The median age of earliest known ASD diagnosis was 49 months and ranged from 36 months in California to 59 months in Minnesota.Among the 4,165 (66.7%) children with ASD with information on cognitive ability, 37.9% were classified as having an intellectual disability. Intellectual disability was present among 50.8% of Black, 41.5% of A/PI, 37.8% of two or more races, 34.9% of Hispanic, 34.8% of AI/AN, and 31.8% of White children with ASD. Overall, children with intellectual disability had earlier median ages of ASD diagnosis (43 months) than those without intellectual disability (53 months). INTERPRETATION: For 2020, one in 36 children aged 8 years (approximately 4% of boys and 1% of girls) was estimated to have ASD. These estimates are higher than previous ADDM Network estimates during 2000-2018. For the first time among children aged 8 years, the prevalence of ASD was lower among White children than among other racial and ethnic groups, reversing the direction of racial and ethnic differences in ASD prevalence observed in the past. Black children with ASD were still more likely than White children with ASD to have a co-occurring intellectual disability. PUBLIC HEALTH ACTION: The continued increase among children identified with ASD, particularly among non-White children and girls, highlights the need for enhanced infrastructure to provide equitable diagnostic, treatment, and support services for all children with ASD. Similar to previous reporting periods, findings varied considerably across network sites, indicating the need for additional research to understand the nature of such differences and potentially apply successful identification strategies across states.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2020. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring Network is an active surveillance program that estimates prevalence and characteristics of ASD and monitors timing of ASD identification among children aged 4 and 8 years. In 2020, a total of 11 sites (located in Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin) conducted surveillance of ASD among children aged 4 and 8 years and suspected ASD among children aged 4 years. Surveillance included children who lived in the surveillance area at any time during 2020. Children were classified as having ASD if they ever received 1) an ASD diagnostic statement in an evaluation, 2) a special education classification of autism (eligibility), or 3) an ASD International Classification of Diseases (ICD) code (revisions 9 or 10). Children aged 4 years were classified as having suspected ASD if they did not meet the case definition for ASD but had a documented qualified professional's statement indicating a suspicion of ASD. This report focuses on children aged 4 years in 2020 compared with children aged 8 years in 2020. RESULTS: For 2020, ASD prevalence among children aged 4 years varied across sites, from 12.7 per 1,000 children in Utah to 46.4 in California. The overall prevalence was 21.5 and was higher among boys than girls at every site. Compared with non-Hispanic White children, ASD prevalence was 1.8 times as high among Hispanic, 1.6 times as high among non-Hispanic Black, 1.4 times as high among Asian or Pacific Islander, and 1.2 times as high among multiracial children. Among the 58.3% of children aged 4 years with ASD and information on intellectual ability, 48.5% had an IQ score of ≤70 on their most recent IQ test or an examiner's statement of intellectual disability. Among children with a documented developmental evaluation, 78.0% were evaluated by age 36 months. Children aged 4 years had a higher cumulative incidence of ASD diagnosis or eligibility by age 48 months compared with children aged 8 years at all sites; risk ratios ranged from 1.3 in New Jersey and Utah to 2.0 in Tennessee. In the 6 months before the March 2020 COVID-19 pandemic declaration by the World Health Organization, there were 1,593 more evaluations and 1.89 more ASD identifications per 1,000 children aged 4 years than children aged 8 years received 4 years earlier. After the COVID-19 pandemic declaration, this pattern reversed: in the 6 months after pandemic onset, there were 217 fewer evaluations and 0.26 fewer identifications per 1,000 children aged 4 years than children aged 8 years received 4 years earlier. Patterns of evaluation and identification varied among sites, but there was not recovery to pre-COVID-19 pandemic levels by the end of 2020 at most sites or overall. For 2020, prevalence of suspected ASD ranged from 0.5 (California) to 10.4 (Arkansas) per 1,000 children aged 4 years, with an increase from 2018 at five sites (Arizona, Arkansas, Maryland, New Jersey, and Utah). Demographic and cognitive characteristics of children aged 4 years with suspected ASD were similar to children aged 4 years with ASD. INTERPRETATION: A wide range of prevalence of ASD by age 4 years was observed, suggesting differences in early ASD identification practices among communities. At all sites, cumulative incidence of ASD by age 48 months among children aged 4 years was higher compared with children aged 8 years in 2020, indicating improvements in early identification of ASD. Higher numbers of evaluations and rates of identification were evident among children aged 4 years until the COVID-19 pandemic onset in 2020. Sustained lower levels of ASD evaluations and identification seen at a majority of sites after the pandemic onset could indicate disruptions in typical practices in evaluations and identification for health service providers and schools through the end of 2020. Sites with more recovery could indicate successful strategies to mitigate service interruption, such as pivoting to telehealth approaches for evaluation. PUBLIC HEALTH ACTION: From 2016 through February of 2020, ASD evaluation and identification among the cohort of children aged 4 years was outpacing ASD evaluation and identification 4 years earlier (from 2012 until March 2016) among the cohort of children aged 8 years in 2020 . From 2016 to March 2020, ASD evaluation and identification among the cohort of children aged 4 years was outpacing that among children aged 8 years in 2020 from 2012 until March 2016. The disruptions in evaluation that coincided with the start of the COVID-19 pandemic and the increase in prevalence of suspected ASD in 2020 could have led to delays in ASD identification and interventions. Communities could evaluate the impact of these disruptions as children in affected cohorts age and consider strategies to mitigate service disruptions caused by future public health emergencies.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2018. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring (ADDM) Network conducts active surveillance of ASD. This report focuses on the prevalence and characteristics of ASD among children aged 8 years in 2018 whose parents or guardians lived in 11 ADDM Network sites in the United States (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin). To ascertain ASD among children aged 8 years, ADDM Network staff review and abstract developmental evaluations and records from community medical and educational service providers. In 2018, children met the case definition if their records documented 1) an ASD diagnostic statement in an evaluation (diagnosis), 2) a special education classification of ASD (eligibility), or 3) an ASD International Classification of Diseases (ICD) code. RESULTS: For 2018, across all 11 ADDM sites, ASD prevalence per 1,000 children aged 8 years ranged from 16.5 in Missouri to 38.9 in California. The overall ASD prevalence was 23.0 per 1,000 (one in 44) children aged 8 years, and ASD was 4.2 times as prevalent among boys as among girls. Overall ASD prevalence was similar across racial and ethnic groups, except American Indian/Alaska Native children had higher ASD prevalence than non-Hispanic White (White) children (29.0 versus 21.2 per 1,000 children aged 8 years). At multiple sites, Hispanic children had lower ASD prevalence than White children (Arizona, Arkansas, Georgia, and Utah), and non-Hispanic Black (Black) children (Georgia and Minnesota). The associations between ASD prevalence and neighborhood-level median household income varied by site. Among the 5,058 children who met the ASD case definition, 75.8% had a diagnostic statement of ASD in an evaluation, 18.8% had an ASD special education classification or eligibility and no ASD diagnostic statement, and 5.4% had an ASD ICD code only. ASD prevalence per 1,000 children aged 8 years that was based exclusively on documented ASD diagnostic statements was 17.4 overall (range: 11.2 in Maryland to 29.9 in California). The median age of earliest known ASD diagnosis ranged from 36 months in California to 63 months in Minnesota. Among the 3,007 children with ASD and data on cognitive ability, 35.2% were classified as having an intelligence quotient (IQ) score ≤70. The percentages of children with ASD with IQ scores ≤70 were 49.8%, 33.1%, and 29.7% among Black, Hispanic, and White children, respectively. Overall, children with ASD and IQ scores ≤70 had earlier median ages of ASD diagnosis than children with ASD and IQ scores >70 (44 versus 53 months). INTERPRETATION: In 2018, one in 44 children aged 8 years was estimated to have ASD, and prevalence and median age of identification varied widely across sites. Whereas overall ASD prevalence was similar by race and ethnicity, at certain sites Hispanic children were less likely to be identified as having ASD than White or Black children. The higher proportion of Black children compared with White and Hispanic children classified as having intellectual disability was consistent with previous findings. PUBLIC HEALTH ACTION: The variability in ASD prevalence and community ASD identification practices among children with different racial, ethnic, and geographical characteristics highlights the importance of research into the causes of that variability and strategies to provide equitable access to developmental evaluations and services. These findings also underscore the need for enhanced infrastructure for diagnostic, treatment, and support services to meet the needs of all children.

OBJECTIVE: Early identification can improve outcomes for children with autism spectrum disorder (ASD). We sought to assess changes in early ASD identification over time and by co-occurring intellectual disability (ID) and race/ethnicity. METHOD: Using data for 2002 through 2016 from a biennial population-based ASD surveillance program among 8-year-old children in the United States, we defined identification as a child's earliest recorded ASD diagnosis or special education eligibility. Unidentified children had characteristics meeting the ASD surveillance case definition but no recorded identification by age 8 years. We calculated median age at identification among identified children, median age at identification including unidentified children, and cumulative incidence of identification by age 48 months. RESULTS: ASD identification by age 48 months was four times (95% CI: 3.6-4.3) as likely in 2016 as 2002, with the largest increases among children without ID. Median age at ASD identification among identified children decreased 3 months during this time. Children of every race/ethnicity were more likely to be identified over time. There were racial disparities stratified by ID: in 2016, Black and Hispanic children without ID were less likely to be identified with ASD than White children (both groups risk ratio: 0.7; 95% CI: 0.5-0.8), but Black children were 1.5 times (95% CI:1.3-1.9) as likely as White children to be identified with ASD and ID. CONCLUSION: Substantial progress has been made to identify more children with ASD early, despite minimal decrease in median age at diagnosis. Considerable disparities remain in early ASD identification by race/ethnicity and co-occurring intellectual disability.

The failure to mount an antibody response following viral infection or seroconversion failure is a largely underappreciated and poorly understood phenomenon. Here, we identified immunologic markers associated with robust antibody responses after influenza virus infection in two independent human cohorts, SHIVERS and FLU09, based in Auckland, New Zealand and Memphis, Tennessee, USA, respectively. In the SHIVERS cohort, seroconversion significantly associates with (1) hospitalization, (2) greater numbers of proliferating, activated CD4+ T cells, but not CD8+ T cells, in the periphery during the acute phase of illness, and (3) fewer inflammatory monocytes (CD14hiCD16+) by convalescence. In the FLU09 cohort, fewer CD14hiCD16+ monocytes during early illness in the nasal mucosa were also associated with the generation of influenza-specific mucosal immunoglobulin A (IgA) and IgG antibodies. Our study demonstrates that seroconversion failure after infection is a definable immunological phenomenon, associated with quantifiable cellular markers that can be used to improve diagnostics, vaccine efficacy, and epidemiologic efforts.

BACKGROUND: Respiratory syncytial virus (RSV) is increasingly recognized as an important cause of illness in adults; however, data on RSV disease and economic burden in this age group remain limited. We aimed to provide comprehensive estimates of RSV disease burden among adults aged ≥18 years. METHODS: During 2012-2015, population-based, active surveillance of acute respiratory infection (ARI) hospitalizations enabled estimation of the seasonal incidence of RSV hospitalizations and direct health costs in adults aged ≥18 years in Auckland, New Zealand. RESULTS: Of 4,600 ARI hospitalizations tested for RSV, 348 (7.6%) were RSV positive. The median (interquartile range) length of hospital stay for RSV positive patients was 4 (2-6) days. The seasonal incidence rate (IR) of RSV hospitalizations, corrected for non-testing, was 23.6 (95% confidence intervals [CI] 21.0-26.1) per 100,000 adults aged ≥18 years. Hospitalization risk increased with age with the highest incidence among adults aged ≥80 years (IR 190.8 per 100,000, 95% CI 137.6-244.0). Being of Māori or Pacific ethnicity or living in a neighborhood with low socioeconomic status (SES) were independently associated with increased RSV hospitalization rates. We estimate RSV-associated hospitalizations among adults aged ≥18 years to cost on average NZD $4,758 per event. CONCLUSIONS: RSV infection is associated with considerable disease and economic cost in adults. RSV disproportionally affects adult sub-groups defined by age, ethnicity, and neighborhood SES. An effective RSV vaccine or RSV treatment may offer benefits for older adults.

Vaccination has transformed public health, most notably including the eradication of smallpox. Despite its profound historical importance, little is known of the origins and diversity of the viruses used in smallpox vaccination. Prior to the twentieth century, the method, source and origin of smallpox vaccinations remained unstandardised and opaque. We reconstruct and analyse viral vaccine genomes associated with smallpox vaccination from historical artefacts. Significantly, we recover viral molecules through non-destructive sampling of historical materials lacking signs of biological residues. We use the authenticated ancient genomes to reveal the evolutionary relationships of smallpox vaccination viruses within the poxviruses as a whole.

U.S. national and state population-based estimates of adults living with autism spectrum disorder (ASD) are nonexistent due to the lack of existing surveillance systems funded to address this need. Therefore, we estimated national and state prevalence of adults 18-84 years living with ASD using simulation in conjunction with Bayesian hierarchal models. In 2017, we estimated that approximately 2.21% (95% simulation interval (SI) 1.95%, 2.45%) or 5,437,988 U.S. adults aged 18 and older have ASD, with state prevalence ranging from 1.97% (95% SI 1.55%, 2.45%) in Louisiana to 2.42% (95% SI 1.93%, 2.99%) in Massachusetts. Prevalence and case estimates of adults living with ASD (diagnosed and undiagnosed) can help states estimate the need for diagnosing and providing services to those unidentified.

Contaminants such as heavy metals may contribute to the dissemination of antimicrobial resistance (AMR) by enriching resistance gene determinants via co-selection mechanisms. In the present study, a survey was performed on soils collected from four areas at the Savannah River Site (SRS), South Carolina, USA, with varying contaminant profiles: relatively pristine (Upper Three Runs), heavy metals (Ash Basins), radionuclides (Pond B) and heavy metal and radionuclides (Tim's Branch). Using 16S rRNA gene amplicon sequencing, we explored the structure and diversity of soil bacterial communities. Sites with legacies of metal and/or radionuclide contamination displayed significantly lower bacterial diversity compared to the reference site. Metagenomic analysis indicated that multidrug and vancomycin antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) including those associated with copper, arsenic, iron, nickel and zinc were prominent in all soils including the reference site. However, significant differences were found in the relative abundance and diversity of certain ARGs and MRGs in soils with metal/radionuclide contaminated soils compared to the reference site. Co-occurrence patterns revealed significant ARG/MRG subtypes in predominant soil taxa including Acidobacteriaceae, Bradyrhizobium, Mycobacterium, Streptomyces, Verrumicrobium, Actinomadura and Solirubacterales. Overall, the study emphasizes the potential risk of human activities on the dissemination of AMR in the environment.

BACKGROUND: Severe influenza illness is presumed more common in adults with chronic medical conditions (CMC), but evidence is sparse and often combined into broad CMC categories. METHODS: Residents (aged 18-80 years) of Central and South Auckland hospitalized for WHO-defined severe acute respiratory illness (SARI) (2012-2015) underwent influenza virus PCR testing. CMC statuses for Auckland residents were modelled using hospitalization ICD-10 codes, pharmaceutical claims, and laboratory results. Population-level influenza rates in adults with congestive heart failure (CHF), coronary artery disease (CAD), cerebrovascular accidents (CVA), chronic obstructive pulmonary disease (COPD), asthma, diabetes mellitus (DM), and end-stage renal disease (ESRD) were calculated by Poisson regression stratified by age and adjusted for ethnicity. RESULTS: Among 891,276 adults, 2,435 influenza-associated SARI hospitalizations occurred. Rates were significantly higher in those with CMCs compared with those without the respective CMC except older adults with DM or those aged <65 years with CVA. The largest effects occurred with CHF (Incidence Rate Ratio [IRR] range: 4.84-13.4 across age strata), ESRD (IRR range: 3.30-9.02), CAD (IRR range= 2.77-10.7), and COPD (IRR range: 5.89-8.78) and tapered with age. CONCLUSIONS: Our findings support the increased risk of severe, laboratory-confirmed influenza disease among adults with specific CMCs compared those without these conditions.

Background: Pregnant women are prioritised for seasonal influenza vaccination however, evidence on influenza risk during pregnancy used to inform these policies is limited. Methods: Individual-level administrative datasets and active surveillance data were joined to estimate influenza-associated hospitalisation and outpatient visit rates by pregnancy, post-partum and trimester status. Results: During 2012-2015, 46 (17.7%) of 260 influenza-confirmed acute respiratory hospitalisations and 13 (4.4%) of 294 influenza-confirmed outpatient visits were among pregnant and post-partum women. Pregnant and post-partum women experienced higher rates of influenza hospitalisation compared with non-pregnant women overall (Rate Ratio [RR] 3.4; 95% Confidence Interval [CI] 2.5-4.7) and by trimester (1st: 2.5; 95%CI 1.2-5.4; 2nd: 3.9; 95%CI 2.4-6.3; 3rd: 4.8; 95%CI 3.0-7.7; post-partum: 0.7; 95%CI 3.0-7.7). Influenza A viruses were associated with increased risk (A(H1N1)pdm09: 5.3; 95%CI 3.2-8.7 and A(H3N2): 3.0; 95%CI 1.8-5.0), but not influenza B (1.8; 95%CI 0.7-4.6). Influenza hospitalisation rates in pregnancy were significantly higher for Maori women (RR 3.2; 95% CI 1.3-8.4) compared with women of European/Other ethnicity. Similar risks for influenza-confirmed outpatient visits were not observed. Conclusion: Seasonal influenza poses higher risks of hospitalisation on pregnant women in all trimesters when compared with non-pregnant women. Hospitalisation rates vary by influenza type and ethnicity among pregnant women.

BACKGROUND: Little is known about inactivated influenza vaccine effectiveness (IVE) in preventing very severe disease, including influenza-associated intensive care unit (ICU) admissions. METHODS: The Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) project enrolled adults (aged>/=18years) with acute respiratory illness (ARI) in general ward (GW) hospital settings (n=3034) and ICUs (n=101) during 2012-2015. IVE was assessed using a test-negative design comparing the odds of influenza vaccination among influenza positives vs. negatives (confirmed by real-time reverse transcription polymerase chain reaction). All models were adjusted for season, weeks from season peak, and a vaccination propensity score. RESULTS: Influenza virus infection was confirmed in 28% of GW hospital and 41% of ICU patients; influenza vaccination was documented for 56% and 41%, respectively. Across seasons, IVE was 37% (95% confidence intervals [CI]=23-48%) among GW patients and 82% (95% CI=45-94%) among ICU patients. IVE point estimates were>70% against ICU influenza and consistently higher than IVE against GW influenza when stratified by season, by virus (sub)types, and for adults with or without chronic medical conditions and for both adults aged <65 and >/=65years old. Among hospitalized influenza positives, influenza vaccination was associated with a 59% reduction in the odds of ICU admission (aOR=0.41, 95% CI=0.18-0.96) and with shorter ICU lengths of stay (LOS), but not with radiograph-confirmed pneumonia or GW hospital LOS. CONCLUSION: Inactivated influenza vaccines prevented influenza-associated ICU admissions, may have higher effectiveness in ICU than GW hospital settings, and appeared to reduce the risk of severe disease among those who are infected despite vaccination.

Background: Understanding the attack rate of influenza infection and the proportion who become ill by risk group is key to implementing prevention measures. While population-based studies of anti-haemagglutinin antibody responses have been described previously, studies examining both anti-haemagglutinin and anti-neuraminidase antibodies are lacking. Methods: In 2015, we conducted a sero-epidemiologic cohort study of individuals randomly selected from a population in New Zealand. We tested paired sera for haemagglutinin-inhibition (HAI) or neuraminidase-inhibition (NAI) titres for seroconversion . We followed participants weekly and performed influenza PCR for those reporting influenza-like illness (ILI). Results: Influenza infection (either HAI or NAI seroconversion) was found in 321 (35%; 95%CI:32-38%) of 911 unvaccinated participants, of which 100 (31%) seroconverted to NAI alone. Young children and Pacific peoples experienced the highest influenza infection attack rates, but overall only a quarter of all infected reported influenza-PCR-confirmed ILI and one-quarter of these sought medical attention. Seroconversion to NAI alone was higher among children aged <5 years vs. those aged >/=5 years (14% vs 4%; p<0.001) and among those with influenza B vs A(H3N2) virus infections (7% vs 0.3%; p<0.001). Conclusions: Measurement of anti-neuraminidase antibodies in addition to anti- hemagglutinin antibodies may be important in capturing the true influenza infection rates.

BACKGROUND: The term severe acute respiratory infection (SARI) encompasses a heterogeneous group of respiratory illnesses. Grading the severity of SARI is currently reliant on indirect disease severity measures such as respiratory and heart rate, and the need for oxygen or intensive care. With the lungs being the primary organ system involved in SARI, chest radiographs (CXRs) are potentially useful for describing disease severity. Our objective was to develop and validate a SARI CXR severity scoring system. METHODS: We completed validation within an active SARI surveillance project, with SARI defined using the World Health Organization case definition of an acute respiratory infection with a history of fever, or measured fever of ≥ 38 degrees C; and cough; and with onset within the last 10 days; and requiring hospital admission. We randomly selected 250 SARI cases. Admission CXR findings were categorized as: 1 = normal; 2 = patchy atelectasis and/or hyperinflation and/or bronchial wall thickening; 3 = focal consolidation; 4 = multifocal consolidation; and 5 = diffuse alveolar changes. Initially, four radiologists scored CXRs independently. Subsequently, a pediatrician, physician, two residents, two medical students, and a research nurse independently scored CXR reports. Inter-observer reliability was determined using a weighted Kappa (kappa) for comparisons between radiologists; radiologists and clinicians; and clinicians. Agreement was defined as moderate (kappa > 0.4-0.6), good (kappa > 0.6-0.8) and very good (kappa > 0.8-1.0). RESULTS: Agreement between the two pediatric radiologists was very good (kappa = 0.83, 95 % CI 0.65-1.00) and between the two adult radiologists was good (kappa = 0.75, 95 % CI 0.57-0. 93). Agreement of the clinicians with the radiologists was moderate-to-good (pediatrician:kappa = 0.65; pediatric resident:kappa = 0.69; physician:kappa = 0.68; resident:kappa = 0.67; research nurse:kappa = 0.49, medical students: kappa = 0.53 and kappa = 0.56). Agreement between clinicians was good-to-very good (pediatrician vs. physician:kappa = 0.85; vs. pediatric resident:kappa = 0.81; vs. medicine resident:kappa = 0.76; vs. research nurse:kappa = 0.75; vs. medical students:kappa = 0.63 and 0.66). Following review of discrepant CXR report scores by clinician pairs, kappa values for radiologist-clinician agreement ranged from 0.59 to 0.70 and for clinician-clinician agreement from 0.97 to 0.99. CONCLUSIONS: This five-point CXR scoring tool, suitable for use in poorly- and well-resourced settings and by clinicians of varying experience levels, reliably describes SARI severity. The resulting numerical data enables epidemiological comparisons of SARI severity between different countries and settings.

INTRODUCTION AND SETTING: Our analysis compares the most comprehensive epidemiologic and virologic surveillance data compiled to date for laboratory-confirmed H1N1pdm patients between 1 April 2009 - 31 January 2010 from five temperate countries in the Southern Hemisphere-Argentina, Australia, Chile, New Zealand, and South Africa. OBJECTIVE: We evaluate transmission dynamics, indicators of severity, and describe the co-circulation of H1N1pdm with seasonal influenza viruses. RESULTS: In the five countries, H1N1pdm became the predominant influenza strain within weeks of initial detection. South Africa was unique, first experiencing a seasonal H3N2 wave, followed by a distinct H1N1pdm wave. Compared with the 2007 and 2008 influenza seasons, the peak of influenza-like illness (ILI) activity in four of the five countries was 3-6 times higher with peak ILI consultation rates ranging from 35/1,000 consultations/week in Australia to 275/100,000 population/week in New Zealand. Transmission was similar in all countries with the reproductive rate ranging from 1.2-1.6. The median age of patients in all countries increased with increasing severity of disease, 4-14% of all hospitalized cases required critical care, and 26-68% of fatal patients were reported to have ≥1 chronic medical condition. Compared with seasonal influenza, there was a notable downward shift in age among severe cases with the highest population-based hospitalization rates among children <5 years old. National population-based mortality rates ranged from 0.8-1.5/100,000. CONCLUSIONS: The difficulty experienced in tracking the progress of the pandemic globally, estimating its severity early on, and comparing information across countries argues for improved routine surveillance and standardization of investigative approaches and data reporting methods.