Impact of the COVID-19 related border restrictions on influenza and other common respiratory viral infections in New Zealand.

BACKGROUND: New Zealand's (NZ) complete absence of community transmission of influenza and respiratory syncytial virus (RSV) after May 2020, likely due to COVID-19 elimination measures, provided a rare opportunity to assess the impact of border restrictions on common respiratory viral infections over the ensuing 2 years. METHODS: We collected the data from multiple surveillance systems, including hospital-based severe acute respiratory infection surveillance, SHIVERS-II, -III and -IV community cohorts for acute respiratory infection (ARI) surveillance, HealthStat sentinel general practice (GP) based influenza-like illness surveillance and SHIVERS-V sentinel GP-based ARI surveillance, SHIVERS-V traveller ARI surveillance and laboratory-based surveillance. We described the data on influenza, RSV and other respiratory viral infections in NZ before, during and after various stages of the COVID related border restrictions. RESULTS: We observed that border closure to most people, and mandatory government-managed isolation and quarantine on arrival for those allowed to enter, appeared to be effective in keeping influenza and RSV infections out of the NZ community. Border restrictions did not affect community transmission of other respiratory viruses such as rhinovirus and parainfluenza virus type-1. Partial border relaxations through quarantine-free travel with Australia and other countries were quickly followed by importation of RSV in 2021 and influenza in 2022. CONCLUSION: Our findings inform future pandemic preparedness and strategies to model and manage the impact of influenza and other respiratory viral threats.

Circulation of influenza and other respiratory viruses during the COVID-19 pandemic in Australia and New Zealand, 2020-2021.

Objective: Circulation patterns of influenza and other respiratory viruses have been globally disrupted since the emergence of coronavirus disease (COVID-19) and the introduction of public health and social measures (PHSMs) aimed at reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Methods: We reviewed respiratory virus laboratory data, Google mobility data and PHSMs in five geographically diverse regions in Australia and New Zealand. We also described respiratory virus activity from January 2017 to August 2021. Results: We observed a change in the prevalence of circulating respiratory viruses following the emergence of SARS-CoV-2 in early 2020. Influenza activity levels were very low in all regions, lower than those recorded in 2017-2019, with less than 1% of laboratory samples testing positive for influenza virus. In contrast, rates of human rhinovirus infection were increased. Respiratory syncytial virus (RSV) activity was delayed; however, once it returned, most regions experienced activity levels well above those seen in 2017-2019. The timing of the resurgence in the circulation of both rhinovirus and RSV differed within and between the two countries. Discussion: The findings of this study suggest that as domestic and international borders are opened up and other COVID-19 PHSMs are lifted, clinicians and public health professionals should be prepared for resurgences in influenza and other respiratory viruses. Recent patterns in RSV activity suggest that these resurgences in non-COVID-19 viruses have the potential to occur out of season and with increased impact.

Sensitivity and specificity of surveillance case definitions in detection of influenza and respiratory syncytial virus among hospitalized patients, New Zealand, 2012-2016.

BACKGROUND: The WHO is exploring the value of adding RSV testing to existing influenza surveillance systems to inform RSV control programs. We evaluate the usefulness of four commonly used influenza surveillance case-definitions for influenza and RSV surveillance. METHODS: SHIVERS, a multi-institutional collaboration, conducted surveillance for influenza and RSV in four New Zealand hospitals. Nurses reviewed admission logs, enrolled patients with suspected acute respiratory infections (ARI), and obtained nasopharyngeal swabs for RT-PCR. We compared the performance characteristics for identifying laboratory-confirmed influenza and RSV severe acute respiratory infection (SARI), defined as persons admitted with measured or reported fever and cough within 10 days of illness, to three other case definitions: 1. reported fever and cough or shortness of breath, 2. cough and shortness of breath, or 3. cough. RESULTS: During April-September 2012-2016, SHIVERS identified 16,055 admissions with ARI; of 6374 cases consented and tested for influenza or RSV, 5437 (85%) had SARI and 937 (15%) did not. SARI had the highest specificity in detecting influenza (40.6%) and RSV (40.8%) but the lowest sensitivity (influenza 78.8%, RSV 60.3%) among patients of all ages. Cough or shortness of breath had the highest sensitivity (influenza 99.3%, RSV 99.9%) but the lowest specificity (influenza 1.6%, RSV 1.9%). SARI sensitivity among children aged <3 months was 60.8% for influenza and 43.6% for RSV-both lower than in other age groups. CONCLUSIONS: While SARI had the highest specificity, its sensitivity was limited, especially among children aged <3 months. Cough or shortness of breath was the most sensitive.

Modelling the impact of respiratory syncytial virus (RSV) vaccine and immunoprophylaxis strategies in New Zealand.

BACKGROUND: Mathematical models of respiratory syncytial virus (RSV) transmission can help describe seasonal epidemics and assess the impact of potential vaccines and immunoprophylaxis with monoclonal antibodies (mAb). METHODS: We developed a deterministic, compartmental model for RSV transmission, which was fitted to population-based RSV hospital surveillance data from Auckland, New Zealand. The model simulated the introduction of either a maternal vaccine or a seasonal mAb among infants aged less than 6 months and estimated the reduction in RSV hospitalizations for a range of effectiveness and coverage values. RESULTS: The model accurately reproduced the annual seasonality of RSV epidemics in Auckland. We found that a maternal vaccine with effectiveness of 30-40% in the first 90 days and 15-20% for the next 90 days could reduce RSV hospitalizations by 18-24% in children younger than 3 months, by 11-14% in children aged 3-5 months, and by 2-3% in children aged 6-23 months. A seasonal infant mAb with 40-60% effectiveness for 150 days could reduce RSV hospitalizations by 30-43%, 34-48% and by 14-21% in children aged 0-2 months, 3-5 months and 6-23 months, respectively. CONCLUSIONS: Our results suggest that either a maternal RSV vaccine or mAb would effectively reduce RSV hospitalization disease burden in New Zealand. Overall, a seasonal mAb resulted in a larger disease prevention impact than a maternal vaccine.

Impact of the COVID-19 nonpharmaceutical interventions on influenza and other respiratory viral infections in New Zealand.

Stringent nonpharmaceutical interventions (NPIs) such as lockdowns and border closures are not currently recommended for pandemic influenza control. New Zealand used these NPIs to eliminate coronavirus disease 2019 during its first wave. Using multiple surveillance systems, we observed a parallel and unprecedented reduction of influenza and other respiratory viral infections in 2020. This finding supports the use of these NPIs for controlling pandemic influenza and other severe respiratory viral threats.

Respiratory Syncytial Virus-Associated Hospitalizations Among Adults With Chronic Medical Conditions.

BACKGROUND: In contrast with respiratory disease caused by influenza, information on the risk of respiratory syncytial virus (RSV) disease among adults with chronic medical conditions (CMCs) is limited. METHODS: We linked population-based surveillance of acute respiratory illness hospitalizations to national administrative data to estimate seasonal RSV hospitalization rates among adults aged 18-80 years with the following preexisting CMCs: chronic obstructive pulmonary disease (COPD), asthma, congestive heart failure (CHF), coronary artery disease (CAD), cerebrovascular accidents (CVA), diabetes mellitus (DM), and end-stage renal disease (ESRD). Age- and ethnicity-adjusted rates stratified by age group were estimated. RESULTS: Among 883 999 adult residents aged 18-80 years, 281 RSV-positive hospitalizations were detected during 2012-2015 winter seasons. Across all ages, RSV hospitalization rates were significantly higher among adults with COPD, asthma, CHF, and CAD compared with those without each corresponding condition. RSV hospitalization rates were significantly higher among adults with ESRD aged 50-64 years and adults with DM aged 18-49 years and 65-80 years compared with adults in each age group without these conditions. No increased risk was seen for adults with CVA. The CMC with the highest risk of RSV hospitalization was CHF (incidence rate ratio [IRR] range, 4.6-36.5 across age strata) and COPD (IRR range, 9.6-9.7). Among RSV-positive adults, CHF and COPD were independently associated with increased length of hospital stay. CONCLUSIONS: Adults with specific CMCs are at increased risk of RSV hospitalizations. Age affects this relationship for some CMCs. Such populations maybe relevant for future RSV prevention strategies.

COVID-19 and Infant Hospitalizations for Seasonal Respiratory Virus Infections, New Zealand, 2020.

In March 2020, a national elimination strategy for coronavirus disease was introduced in New Zealand. Since then, hospitalizations for lower respiratory tract infection among infants <2 years of age and cases of respiratory syncytial or influenza virus infection have dramatically decreased. These findings indicate additional benefits of coronavirus disease control strategies.

Impact of oral corticosteroids on respiratory outcomes in acute preschool wheeze: a randomised clinical trial.

OBJECTIVE: To determine if administration of oral prednisolone to preschool children with acute wheeze alters respiratory outcomes. DESIGN: Double-blind, randomised, placebo-controlled equivalence trial. SETTING: Three hospitals in New Zealand. PATIENTS: 477 children aged 24-59 months with acute wheeze associated with respiratory illness. INTERVENTIONS: 2 mg/kg (maximum 40 mg) oral prednisolone or similar placebo, once daily for 3 days. MAIN OUTCOME MEASURES: Primary outcome was change in Preschool Respiratory Assessment Measure (PRAM) score 24 hours after intervention. Secondary outcomes included PRAM score at 4 hours, length of emergency department and inpatient stays, admission and representation rates, time to return to normal activities and use of additional oral prednisolone or intravenous medications. Analysis was by intention-to-treat. RESULTS: There was no difference between groups for change in PRAM score at 24 hours (difference between means -0.39, 95% CI -0.84 to 0.06, p=0.09). Absolute PRAM score was lower in the prednisolone group at 4 hours (median (IQR) 1 (0-2) vs 2 (0-3), p=0.01) and 24 hours (0 (0-1) vs 0 (0-1), p=0.01), when symptoms had resolved for most children regardless of initial treatment. Admission rate, requirement for additional oral prednisolone and use of intravenous medication were lower in the prednisolone group, although there were no differences between groups for time taken to return to normal activities or rates of representation within 7 days. CONCLUSION: Oral prednisolone does not alter respiratory outcomes at 24 hours or beyond in preschool children presenting with acute wheeze.

Impact of the COVID-19 nonpharmaceutical interventions on influenza and other respiratory viral infections in New Zealand.

Stringent nonpharmaceutical interventions (NPIs) such as lockdowns and border closures are not currently recommended for pandemic influenza control. New Zealand used these NPIs to eliminate coronavirus disease 2019 during its first wave. Using multiple surveillance systems, we observed a parallel and unprecedented reduction of influenza and other respiratory viral infections in 2020. This finding supports the use of these NPIs for controlling pandemic influenza and other severe respiratory viral threats.

Respiratory Health of Pacific Youth: An Observational Study of Associated Risk and Protective Factors Throughout Childhood.

BACKGROUND: Respiratory disease is the third most common cause of death in New Zealand, with Pacific people living in New Zealand bearing the greatest burden of this type of disease. Although some epidemiological outcomes are known, we lack the specifics required to formulate targeted and effective public health interventions. The Pacific Islands Families (PIF) birth cohort study is a study that provides a unique source of data to assess lung function and current respiratory health among participants entering early adulthood and to examine associations with early life events during critical periods of growth. OBJECTIVE: This paper aims to provide an overview of the design, methods, and scope of the Respiratory Health of Pacific Youth Study, which uses the overall PIF study cohort aged 18-19 years. METHODS: From 2000-2019, the PIF study has followed, from birth, the growth, and the development of 1398 Pacific children born in Auckland, New Zealand. Participants were nested within the overall PIF study (at ages 18-19 years) from June 2018, and assessments were undertaken until mid-November 2019. The assessments included respiratory and general medical histories, a general physical examination, assessment of lung function (forced expiratory volume and forced vital capacity), self-completed questionnaires (St George's Respiratory Questionnaire, European Quality of Life 5 Dimensions-3 Level, Epworth Sleepiness Scale for Children and Adolescents, and Leicester Cough Questionnaire), blood tests (eosinophils, Immunoglobulin E, Immunoglobulin G, Immunoglobulin A, Immunoglobulin M, and C-reactive protein), and chest x-rays. Noninferential analyses will be carried out on dimensionally reduced risk and protective factors and confounders. RESULTS: Data collection began in June 2018 and ended in November 2019, with a total of 466 participants recruited for submission of the paper. Collection and collation of chest x-ray data is still underway, and data analysis and expected results will be published by November 2020. CONCLUSIONS: This is the first longitudinal observational study to address the burden of respiratory disease among Pacific youth by determining factors in early life that impose long-term detriments in lung function and are associated with the presence of respiratory illness. Identifying risk factors and the magnitude of their effects will help in adopting preventative measures, establishing whether any avoidable risks can be modified by later resilient behaviors, and provide baseline measurements for the development of respiratory disease in later adult life. The study results can be translated into practice guidelines and inform health strategies with immediate national and international impact. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18916.

Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants. METHODS: Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%). RESULTS: A total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, -1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, -8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups. CONCLUSIONS: RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.).

Respiratory Virus-related Emergency Department Visits and Hospitalizations Among Infants in New Zealand.

BACKGROUND: Estimates of the contribution of respiratory viruses to emergency department (ED) utilization remain limited. METHODS: We conducted surveillance of infants with acute respiratory infection (ARI) associated ED visits, which then resulted in either hospital admission or discharge home. Seasonal rates of specific viruses stratified by age, ethnicity, and socioeconomic status were estimated for both visits discharged directly from ED and hospitalizations using rates of positivity for each virus. RESULTS: During the 2014-2016 winter seasons, 3585 (66%) of the 5412 ARI ED visits were discharged home directly and 1827 (34%) were admitted to hospital. Among visits tested for all respiratory viruses, 601/1111 (54.1%) of ED-only and 639/870 (73.4%) of the hospital-admission groups were positive for at least one respiratory virus. Overall, respiratory virus-associated ED visit rates were almost twice as high as hospitalizations. Respiratory syncytial virus was associated with the highest ED (34.4 per 1000) and hospitalization rates (24.6 per 1000) among infants. ED visit and hospitalization rates varied significantly by age and virus. Maori and Pacific children had significantly higher ED visit and hospitalization rates for all viruses compared with children of other ethnicities. CONCLUSIONS: Many infants with acute respiratory virus infections are managed in the ED rather than admitted to the hospital. Higher rates of ED-only versus admitted acute respiratory virus infections occur among infants living in lower socioeconomic households, older infants and infants of Maori or Pacific versus European ethnicity. Respiratory virus infections resulting in ED visits should be included in measurements of ARI disease burden.

The health and economic burden of respiratory syncytial virus associated hospitalizations in adults.

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 Maori 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.

Prospective community programme versus parent-driven care to prevent respiratory morbidity in children following hospitalisation with severe bronchiolitis or pneumonia.

BACKGROUND: Hospitalisation with severe lower respiratory tract infection (LRTI) in early childhood is associated with ongoing respiratory symptoms and possible later development of bronchiectasis. We aimed to reduce this intermediate respiratory morbidity with a community intervention programme at time of discharge. METHODS: This randomised, controlled, single-blind trial enrolled children aged <2 years hospitalised for severe LRTI to 'intervention' or 'control'. Intervention was three monthly community clinics treating wet cough with prolonged antibiotics referring non-responders. All other health issues were addressed, and health resilience behaviours were encouraged, with referrals for housing or smoking concerns. Controls followed the usual pathway of parent-initiated healthcare access. After 24 months, all children were assessed by a paediatrician blinded to randomisation for primary outcomes of wet cough, abnormal examination (crackles or clubbing) or chest X-ray Brasfield score ≤22. FINDINGS: 400 children (203 intervention, 197 control) were enrolled in 2011-2012; mean age 6.9 months, 230 boys, 87% Maori/Pasifika ethnicity and 83% from the most deprived quintile. Final assessment of 321/400 (80.3%) showed no differences in presence of wet cough (33.9% intervention, 36.5% controls, relative risk (RR) 0.93, 95% CI 0.69 to 1.25), abnormal examination (21.7% intervention, 23.9% controls, RR 0.92, 95% CI 0.61 to 1.38) or Brasfield score ≤22 (32.4% intervention, 37.9% control, RR 0.85, 95% CI 0.63 to 1.17). Twelve (all intervention) were diagnosed with bronchiectasis within this timeframe. INTERPRETATION: We have identified children at high risk of ongoing respiratory disease following hospital admission with severe LRTI in whom this intervention programme did not change outcomes over 2 years. TRIAL REGISTRATION NUMBER: ACTRN12610001095055.

Respiratory syncytial virus hospitalisations among young children: a data linkage study.

We aimed to provide comprehensive estimates of laboratory-confirmed respiratory syncytial virus (RSV)-associated hospitalisations. Between 2012 and 2015, active surveillance of acute respiratory infection (ARI) hospitalisations during winter seasons was used to estimate the seasonal incidence of laboratory-confirmed RSV hospitalisations in children aged <5 years in Auckland, New Zealand (NZ). Incidence rates were estimated by fine age group, ethnicity and socio-economic status (SES) strata. Additionally, RSV disease estimates determined through active surveillance were compared to rates estimated from hospital discharge codes. There were 5309 ARI hospitalisations among children during the study period, of which 3923 (73.9%) were tested for RSV and 1597 (40.7%) were RSV-positive. The seasonal incidence of RSV-associated ARI hospitalisations, once corrected for non-testing, was 6.1 (95% confidence intervals 5.8-6.4) per 1000 children <5 years old. The highest incidence was among children aged <3 months. Being of indigenous Maori or Pacific ethnicity or living in a neighbourhood with low SES independently increased the risk of an RSV-associated hospitalisation. RSV hospital discharge codes had a sensitivity of 71% for identifying laboratory-confirmed RSV cases. RSV infection is a leading cause of hospitalisation among children in NZ, with significant disparities by ethnicity and SES. Our findings highlight the need for effective RSV vaccines and therapies.

Risk Factors and Attack Rates of Seasonal Influenza Infection: Results of the Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) Seroepidemiologic Cohort Study.

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 antihemagglutinin antibody responses have been described previously, studies examining both antihemagglutinin and antineuraminidase antibodies are lacking. Methods: In 2015, we conducted a seroepidemiologic cohort study of individuals randomly selected from a population in New Zealand. We tested paired sera for hemagglutination inhibition (HAI) or neuraminidase inhibition (NAI) titers for seroconversion. We followed participants weekly and performed influenza polymerase chain reaction (PCR) for those reporting influenza-like illness (ILI). Results: Influenza infection (either HAI or NAI seroconversion) was found in 321 (35% [95% confidence interval, 32%-38%]) of 911 unvaccinated participants, of whom 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 < .001) and among those with influenza B vs A(H3N2) virus infections (7% vs 0.3%; P < .001). Conclusions: Measurement of antineuraminidase antibodies in addition to antihemagglutinin antibodies may be important in capturing the true influenza infection rates.

Evaluation of a sudden unexpected death in infancy intervention programme aimed at improving parental awareness of risk factors and protective infant care practices.

AIM: Sudden unexpected death in infancy (SUDI) rates for Maori and Pacific infants remain higher than for other ethnic groups in New Zealand and bed-sharing is a major risk factor when there is smoking exposure in pregnancy. Sleep space programmes of education and Pepi-Pod baby beds require evaluation. METHODS: Two hundred and forty Maori and Pacific women and infants were randomised 1:1, to the Pepi-Pod sleep space programme, or to a control group with 'usual care'. When infants were under 2 weeks of age, baseline interviews occurred, followed up by interviews at 2 and 4 months of age to assess safe sleep knowledge, infant care practices and Pepi-Pod use and acceptability. All participants were offered a New Zealand Standard approved portable cot. RESULTS: At baseline, 25% of babies did not have a baby bed. Knowledge of smoking and bed-sharing as SUDI risks improved at follow-up in both groups. One quarter regularly bed-shared at follow-up in both groups. Intention to bed-share was a strong predictor of subsequent behaviour. Pepi-Pods were regularly used by 46% at 2 months and 16% at 4 months follow-up. CONCLUSIONS: Bed-sharing and knowledge improvement were similar irrespective of group. It is likely that the impact of the intervention was reduced because the control group received better support than 'usual care' and all participants had a baby bed. New Zealand SUDI rates have declined since sleep space programmes have been available. Sleep space programmes should be prioritised for those with modifiable SUDI risk.