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.

Tracing the international arrivals of SARS-CoV-2 Omicron variants after Aotearoa New Zealand reopened its border.

In the second quarter of 2022, there was a global surge of emergent SARS-CoV-2 lineages that had a distinct growth advantage over then-dominant Omicron BA.1 and BA.2 lineages. By generating 10,403 Omicron genomes, we show that Aotearoa New Zealand observed an influx of these immune-evasive variants (BA.2.12.1, BA.4, and BA.5) through the border. This is explained by the return to significant levels of international travel following the border's reopening in March 2022. We estimate one Omicron transmission event from the border to the community for every ~5,000 passenger arrivals at the current levels of travel and restriction. Although most of these introductions did not instigate any detected onward transmission, a small minority triggered large outbreaks. Genomic surveillance at the border provides a lens on the rate at which new variants might gain a foothold and trigger new waves of infection.

Genomic epidemiology of Delta SARS-CoV-2 during transition from elimination to suppression in Aotearoa New Zealand.

New Zealand's COVID-19 elimination strategy heavily relied on the use of genomics to inform contact tracing, linking cases to the border and to clusters during community outbreaks. In August 2021, New Zealand entered its second nationwide lockdown after the detection of a single community case with no immediately apparent epidemiological link to the border. This incursion resulted in the largest outbreak seen in New Zealand caused by the Delta Variant of Concern. Here we generated 3806 high quality SARS-CoV-2 genomes from cases reported in New Zealand between 17 August and 1 December 2021, representing 43% of reported cases. We detected wide geographical spread coupled with undetected community transmission, characterised by the apparent extinction and reappearance of genomically linked clusters. We also identified the emergence, and near replacement, of genomes possessing a 10-nucleotide frameshift deletion that caused the likely truncation of accessory protein ORF7a. By early October, New Zealand moved from an elimination strategy to a suppression strategy and the role of genomics changed markedly from being used to track and trace, towards population-level surveillance.

Invasive Pneumococcal Disease: Concerning Trends in Serotype 19A Notifications in New Zealand.

New Zealand (NZ) is one of few countries to shift from PCV13 to PCV10. The number of serotype 19A cases in young children and the proportions of isolates that are penicillin-resistant have been steadily increasing since. It is time for NZ to reconsider its choice of pneumococcal vaccine.

Airborne Transmission of SARS-CoV-2 Delta Variant within Tightly Monitored Isolation Facility, New Zealand (Aotearoa).

In New Zealand, international arrivals are quarantined and undergo severe acute respiratory syndrome coronavirus 2 screening; those who test positive are transferred to a managed isolation facility (MIF). Solo traveler A and person E from a 5-person travel group (BCDEF) tested positive. After transfer to the MIF, person A and group BCDEF occupied rooms >2 meters apart across a corridor. Persons B, C, and D subsequently tested positive; viral sequences matched A and were distinct from E. The MIF was the only shared location of persons A and B, C, and D, and they had no direct contact. Security camera footage revealed 4 brief episodes of simultaneous door opening during person A's infectious period. This public health investigation demonstrates transmission from A to B, C, and D while in the MIF, with airborne transmission the most plausible explanation. These findings are of global importance for coronavirus disease public health interventions and infection control practices.

Creating symptom-based criteria for diagnostic testing: a case study based on a multivariate analysis of data collected during the first wave of the COVID-19 pandemic in New Zealand.

BACKGROUND: Diagnostic testing using PCR is a fundamental component of COVID-19 pandemic control. Criteria for determining who should be tested by PCR vary between countries, and ultimately depend on resource constraints and public health objectives. Decisions are often based on sets of symptoms in individuals presenting to health services, as well as demographic variables, such as age, and travel history. The objective of this study was to determine the sensitivity and specificity of sets of symptoms used for triaging individuals for confirmatory testing, with the aim of optimising public health decision making under different scenarios. METHODS: Data from the first wave of COVID-19 in New Zealand were analysed; comprising 1153 PCR-confirmed and 4750 symptomatic PCR negative individuals. Data were analysed using Multiple Correspondence Analysis (MCA), automated search algorithms, Bayesian Latent Class Analysis, Decision Tree Analysis and Random Forest (RF) machine learning. RESULTS: Clinical criteria used to guide who should be tested by PCR were based on a set of mostly respiratory symptoms: a new or worsening cough, sore throat, shortness of breath, coryza, anosmia, with or without fever. This set has relatively high sensitivity (> 90%) but low specificity (< 10%), using PCR as a quasi-gold standard. In contrast, a group of mostly non-respiratory symptoms, including weakness, muscle pain, joint pain, headache, anosmia and ageusia, explained more variance in the MCA and were associated with higher specificity, at the cost of reduced sensitivity. Using RF models, the incorporation of 15 common symptoms, age, sex and prioritised ethnicity provided algorithms that were both sensitive and specific (> 85% for both) for predicting PCR outcomes. CONCLUSIONS:  If predominantly respiratory symptoms are used for test-triaging,  a large proportion of the individuals being tested may not have COVID-19. This could overwhelm testing capacity and hinder attempts to trace and eliminate infection. Specificity can be increased using alternative rules based on sets of symptoms informed by multivariate analysis and automated search algorithms, albeit at the cost of sensitivity. Both sensitivity and specificity can be improved through machine learning algorithms, incorporating symptom and demographic data, and hence may provide an alternative approach to test-triaging that can be optimised according to prevailing conditions.

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.

Genomic Evidence of In-Flight Transmission of SARS-CoV-2 Despite Predeparture Testing.

Since the first wave of coronavirus disease in March 2020, citizens and permanent residents returning to New Zealand have been required to undergo managed isolation and quarantine (MIQ) for 14 days and mandatory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of October 20, 2020, of 62,698 arrivals, testing of persons in MIQ had identified 215 cases of SARS-CoV-2 infection. Among 86 passengers on a flight from Dubai, United Arab Emirates, that arrived in New Zealand on September 29, test results were positive for 7 persons in MIQ. These passengers originated from 5 different countries before a layover in Dubai; 5 had negative predeparture SARS-CoV-2 test results. To assess possible points of infection, we analyzed information about their journeys, disease progression, and virus genomic data. All 7 SARS-CoV-2 genomes were genetically identical, except for a single mutation in 1 sample. Despite predeparture testing, multiple instances of in-flight SARS-CoV-2 transmission are likely.

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.

COVID-19 in New Zealand and the impact of the national response: a descriptive epidemiological study.

BACKGROUND: In early 2020, during the COVID-19 pandemic, New Zealand implemented graduated, risk-informed national COVID-19 suppression measures aimed at disease elimination. We investigated their impacts on the epidemiology of the first wave of COVID-19 in the country and response performance measures. METHODS: We did a descriptive epidemiological study of all laboratory-confirmed and probable cases of COVID-19 and all patients tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in New Zealand from Feb 2 to May 13, 2020, after which time community transmission ceased. We extracted data from the national notifiable diseases database and the national SARS-CoV-2 test results repository. Demographic features and disease outcomes, transmission patterns (source of infection, outbreaks, household transmission), time-to-event intervals, and testing coverage were described over five phases of the response, capturing different levels of non-pharmaceutical interventions. Risk factors for severe outcomes (hospitalisation or death) were examined with multivariable logistic regression and time-to-event intervals were analysed by fitting parametric distributions using maximum likelihood estimation. FINDINGS: 1503 cases were detected over the study period, including 95 (6·3%) hospital admissions and 22 (1·5%) COVID-19 deaths. The estimated case infection rate per million people per day peaked at 8·5 (95% CI 7·6-9·4) during the 10-day period of rapid response escalation, declining to 3·2 (2·8-3·7) in the start of lockdown and progressively thereafter. 1034 (69%) cases were imported or import related, tending to be younger adults, of European ethnicity, and of higher socioeconomic status. 702 (47%) cases were linked to 34 outbreaks. Severe outcomes were associated with locally acquired infection (crude odds ratio [OR] 2·32 [95% CI 1·40-3·82] compared with imported), older age (adjusted OR ranging from 2·72 [1·40-5·30] for 50-64 year olds to 8·25 [2·59-26·31] for people aged ≥80 years compared with 20-34 year olds), aged residential care residency (adjusted OR 3·86 [1·59-9·35]), and Pacific peoples (adjusted OR 2·76 [1·14-6·68]) and Asian (2·15 [1·10-4·20]) ethnicities relative to European or other. Times from illness onset to notification and isolation progressively decreased and testing increased over the study period, with few disparities and increasing coverage of females, Maori, Pacific peoples, and lower socioeconomic groups. INTERPRETATION: New Zealand's response resulted in low relative burden of disease, low levels of population disease disparities, and the initial achievement of COVID-19 elimination. FUNDING: Ministry of Business Innovation and Employment Strategic Scientific Investment Fund, and Ministry of Health, New Zealand.

Heterogeneity in influenza seasonality and vaccine effectiveness in Australia, Chile, New Zealand and South Africa: early estimates of the 2019 influenza season.

We compared 2019 influenza seasonality and vaccine effectiveness (VE) in four southern hemisphere countries: Australia, Chile, New Zealand and South Africa. Influenza seasons differed in timing, duration, intensity and predominant circulating viruses. VE estimates were also heterogeneous, with all-ages point estimates ranging from 7-70% (I2: 33%) for A(H1N1)pdm09, 4-57% (I2: 49%) for A(H3N2) and 29-66% (I2: 0%) for B. Caution should be applied when attempting to use southern hemisphere data to predict the northern hemisphere influenza season.

Cadmium intake and systemic exposure in postmenopausal women and age-matched men who smoke cigarettes.

Mean blood cadmium (B-Cd) concentrations are two- to threefold higher in smokers than in nonsmokers. The basis for this phenomenon is not well understood. We conducted a detailed, multifaceted study of cadmium exposure in smokers. Groups were older smokers (62±4 years, n = 25, 20% male) and nonsmokers (62±3 years, n = 16, 31% male). Each subject's cigarettes were machine smoked, generating individually paired measures of inhaled cadmium (I-Cd) versus B-Cd; I-Cd and B-Cd were each evaluated three times, at monthly intervals. Urine cadmium (U-Cd) was analyzed for comparison. In four smokers, a duplicate-diet study was conducted, along with a kinetic study of plasma cadmium versus B-Cd. Female smokers had a mean B-Cd of 1.21ng Cd/ml, with a nearly 10-fold range (0.29-2.74ng Cd/ml); nonsmokers had a lower mean B-Cd, 0.35ng Cd/ml (p < 0.05), and narrower range (0.20-0.61ng Cd/ml). Means and ranges for males were similar. Estimates of cadmium amounts inhaled daily for our subjects smoking ≥ 20 cigarettes/day were far less than the 15 µg Cd reported to be ingested daily via diet. This I-Cd amount was too low to alone explain the 3.5-fold elevation of B-Cd in our smokers, even assuming greater cadmium absorption via lungs than gastrointestinal tract; cadmium accumulated in smokers' lungs may provide the added cadmium. Finally, B-Cd appeared to be linearly related to I-Cd values in 75% of smokers, whereas 25% had far higher B-Cd, implying a possible heterogeneity among smokers regarding circulating cadmium concentrations and potentially cadmium toxicity.

Critical role of preproenkephalin in experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an organ-specific autoimmune disease model used to investigate mechanisms involved in the activation of self-reactive T cells. Preproenkephalin (PPNK) is the gene that encodes the protein proenkephalin A that has been detected in the brain, adrenal cells and cells of the immune system. In this paper, whether PPNK plays a role in the development of EAE was investigated. PPNK-deficient and wild-type mice were immunized with the MOG(35-55) peptide and the development of EAE observed. Our results show that PPNK-deficient mice developed less severe clinical signs of disease than wild-type mice, and with lower incidence. MOG(35-55)-specific T cells from PPNK-deficient and wild-type mice produced IFNgamma and TNFalpha but no IL-4 or IL-10, indicative of a Th1 phenotype. However, the numbers of MOG(35-55)-specific IFNgamma-producing cells from immunized PPNK-deficient mice were largely reduced at early stages of disease. Interestingly, there was no difference in clinical signs or infiltrating mononuclear cells in the CNS between wild-type and PPNK-deficient mice at the later stage of disease. Our results suggest that PPNK accelerates the generation of autoimmune IFNgamma-producing T cells and MOG(35-55)-induced EAE.

Fcgamma receptor-ligating complexes improve the course of experimental autoimmune encephalomyelitis by enhancing basal Th2 responses.

IL-12p40 and macrophages are essential for the induction of disease in the mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis. In this paper, we show that treatment of mice with opsonized erythrocytes, which have been shown to ligate Fcgamma receptors on macrophages and alter their cytokine profile, significantly delayed the onset of experimental autoimmune encephalomyelitis. This protection correlated to the induction of Th2 responses by autoreactive T cells, enhanced basal systemic responses and a significant downregulation of IL-12p40 and nitric oxide synthase-2, but not IFN-gamma expression. IL-4 was essential for the protection by opsonized erythrocytes as the effects of treatment were eliminated in IL-4-deficient mice. Together these studies suggest that the ligation of Fcgamma receptors can modify the development of autoimmune disease by altering macrophage activation and enhancing Th2 responses.