Reconstructing household transmission dynamics to estimate the infectiousness of asymptomatic influenza virus infections.

There has long been controversy over the potential for asymptomatic cases of the influenza virus to have the capacity for onward transmission, but recognition of asymptomatic transmission of COVID-19 stimulates further research into this topic. Here, we develop a Bayesian methodology to analyze detailed data from a large cohort of 727 households and 2515 individuals in the 2009 pandemic influenza A(H1N1) outbreak in Hong Kong to characterize household transmission dynamics and to estimate the relative infectiousness of asymptomatic versus symptomatic influenza cases. The posterior probability that asymptomatic cases [36% of cases; 95% credible interval (CrI): 32%, 40%] are less infectious than symptomatic cases is 0.82, with estimated relative infectiousness 0.57 (95% CrI: 0.11, 1.54). More data are required to strengthen our understanding of the contribution of asymptomatic cases to the spread of influenza.

Assessing the longitudinal effects of the continuation and discontinuation of the school-located influenza vaccination programme on parental vaccine hesitancy in Hong Kong.

BACKGROUND: School-located influenza vaccination programme (SIVP) can effectively promote childhood seasonal influenza vaccination (SIV). However, the longitudinal effects of continuation and discontinuation of the SIVP on parents' vaccine hesitancy remained unknown. METHODS: A two-wave longitudinal study recruited adult parents who had at least one child attending a kindergarten or primary school using random-digital-dialled telephone interviews. Generalized estimating equation and structural equation modelling were used to examine the impact of changes in schools' SIVP participation status on parents' vaccine-related attitudes, and childhood SIV acceptance over 2 years in Hong Kong. RESULTS: Children's SIV uptake varied by the schools' SIVP participation status. The highest SIV uptake was found in schools that consistently participated in SIVP (Consistent participation group) (2018/2019: 85.0%; 2019/2020: 83.0%) but lowest in the Consistent non-Participation group (2018/2019: 45.0%; 2019/2020: 39.0%). SIV uptake increased in the Late Initiation group but declined in the Discontinuation group. An increasing trend of parental vaccine-hesitant attitudes was observed in the Consistent non-Participation group. CONCLUSIONS: Initiation and continuation of the SIVP can reduce parental vaccine hesitancy to achieve a high childhood SIV uptake. Conversely, discontinuation of the SIVP or persistent resistance to the implementation of SIVP can increase parental vaccine hesitancy and reduce childhood SIV uptake.

Comparative Reactogenicity of Enhanced Influenza Vaccines in Older Adults.

BACKGROUND: We analyzed data from a randomized controlled trial on the reactogenicity of 3 enhanced influenza vaccines compared with standard-dose (SD) inactivated influenza vaccine. METHODS: We enrolled community-dwelling older adults in Hong Kong, and we randomly allocated them to receive 2017-2018 northern hemisphere formulations of SD vaccine (FluQuadri; Sanofi Pasteur), MF59-adjuvanted vaccine (FLUAD; Seqirus), high-dose (HD) vaccine (Fluzone High-Dose; Sanofi Pasteur), or recombinant hemagglutinin vaccine (Flublok; Sanofi Pasteur). Local and systemic reactions were evaluated at days 1, 3, 7, and 14 after vaccination. RESULTS: Reported reactions were generally mild and short-lived. Systemic reactions occurred in similar proportions of participants by vaccine. Some local reactions were slightly more frequently reported among recipients of the MF59-adjuvanted and HD vaccines than among SD vaccine recipients. Participants reporting feverishness 1 day after vaccination had mean fold rises in postvaccination hemagglutination inhibition titers that were 1.85-fold higher (95% confidence interval, 1.01-3.38) for A(H1N1) than in those who did not report feverishness. CONCLUSIONS: Some acute local reactions were more frequent after vaccination with MF59-adjuvanted and HD influenza vaccines, compared with SD inactivated influenza vaccine, whereas systemic symptoms occurred at similar frequencies in all groups. The association between feverishness and immunogenicity should be further investigated in a larger population. CLINICAL TRIALS REGISTRATION: NCT03330132.

Presence of Influenza Virus on Touch Surfaces in Kindergartens and Primary Schools.

BACKGROUNDS: Influenza virus can survive on some surfaces, facilitating indirect person-to-person transmission. METHODS: We collected swab samples weekly from commonly touched surfaces in 7 kindergartens and primary schools during the 2017/2018 winter influenza season in Hong Kong. RESULTS: We detected influenza virus ribonucleic acid (RNA) in 12 of 1352 samples (<1%) collected from 7 of 11 classrooms (5 to 2 × 106 RNA copies/mL). Viral RNA was more frequently recovered from communal items inside classrooms such as bookshelves and doorknobs. CONCLUSIONS: Surface contamination indicates the potential role of fomites in influenza virus transmission in schools. Communal items inside classrooms may cause greater potential risks of transmission during influenza epidemics.

Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial.

BACKGROUND: Enhanced influenza vaccines may improve protection for older adults, but comparative immunogenicity data are limited. Our objective was to examine immune responses to enhanced influenza vaccines, compared to standard-dose vaccines, in community-dwelling older adults. METHODS: Community-dwelling older adults aged 65-82 years in Hong Kong were randomly allocated (October 2017-January 2018) to receive 2017-2018 Northern hemisphere formulations of a standard-dose quadrivalent vaccine, MF59-adjuvanted trivalent vaccine, high-dose trivalent vaccine, or recombinant-hemagglutinin (rHA) quadrivalent vaccine. Sera collected from 200 recipients of each vaccine before and at 30-days postvaccination were assessed for antibodies to egg-propagated vaccine strains by hemagglutination inhibition (HAI) and to cell-propagated A/Hong Kong/4801/2014(H3N2) virus by microneutralization (MN). Influenza-specific CD4+ and CD8+ T cell responses were assessed in 20 participants per group. RESULTS: Mean fold rises (MFR) in HAI titers to egg-propagated A(H1N1) and A(H3N2) and the MFR in MN to cell-propagated A(H3N2) were statistically significantly higher in the enhanced vaccine groups, compared to the standard-dose vaccine. The MFR in MN to cell-propagated A(H3N2) was highest among rHA recipients (4.7), followed by high-dose (3.4) and MF59-adjuvanted (2.9) recipients, compared to standard-dose recipients (2.3). Similarly, the ratio of postvaccination MN titers among rHA recipients to cell-propagated A(H3N2) recipients was 2.57-fold higher than the standard-dose vaccine, which was statistically higher than the high-dose (1.33-fold) and MF59-adjuvanted (1.43-fold) recipient ratios. Enhanced vaccines also resulted in the boosting of T-cell responses. CONCLUSIONS: In this head-to-head comparison, older adults receiving enhanced vaccines showed improved humoral and cell-mediated immune responses, compared to standard-dose vaccine recipients. CLINICAL TRIALS REGISTRATION: NCT03330132.

Increases in absenteeism among health care workers in Hong Kong during influenza epidemics, 2004-2009.

BACKGROUND: Acute respiratory infections (ARI) are a major cause of sickness absenteeism among health care workers (HCWs) and contribute significantly to overall productivity loss particularly during influenza epidemics. The purpose of this study is to quantify the increases in absenteeism during epidemics including the 2009 influenza A(H1N1)pdm09 pandemic. METHODS: We analysed administrative data to determine patterns of sickness absence among HCWs in Hong Kong from January 2004 through December 2009, and used multivariable linear regression model to estimate the excess all-cause and ARI-related sickness absenteeism rates during influenza epidemics. RESULTS: We found that influenza epidemics prior to the 2009 pandemic and during the 2009 pandemic were associated with 8.4 % (95 % CI: 5.6-11.2 %) and 57.7 % (95 % CI: 54.6-60.9 %) increases in overall sickness absence, and 26.5 % (95 % CI: 21.4-31.5 %) and 90.9 % (95 % CI: 85.2-96.6 %) increases in ARI-related sickness absence among HCWs in Hong Kong, respectively. Comparing different staff types, increases in overall absenteeism were highest among medical staff, during seasonal influenza epidemic periods (51.3 %, 95 % CI: 38.9-63.7 %) and the pandemic mitigation period (142.1 %, 95 % CI: 128.0-156.1 %). CONCLUSIONS: Influenza epidemics were associated with a substantial increase in sickness absence and productivity loss among HCWs in Hong Kong, and there was a much higher rate of absenteeism during the 2009 pandemic. These findings could inform better a more proactive workforce redistribution plans to allow for sufficient surge capacity in annual epidemics, and for pandemic preparedness.

Incidence of influenza virus infections in children in Hong Kong in a 3-year randomized placebo-controlled vaccine study, 2009-2012.

BACKGROUND: School-aged children suffer high rates of influenza virus infections and associated illnesses each year, and are a major source of transmission in the community. However, information on the cumulative incidence of infection in specific epidemics is scarce, and there are limited studies with sufficient follow-up to identify the strength and duration of protection against reinfection. METHODS: We randomly allocated children 5-17 years of age to receive trivalent inactivated influenza vaccine (TIV) or placebo from September 2009 through January 2010, and then conducted follow-up for 3 years including regular collection of sera, symptom diaries, and collection of nose and throat swabs during illness episodes in participants or their household members. RESULTS: Of 796 children initially randomized, 484 continued to participate for all 3 years. In unvaccinated children, cumulative incidence of infection was estimated to be 59% in the first wave of H1N1pdm09 in 2009-2010, and 7%, 14%, 20%, and 31% in subsequent epidemics of H3N2 (2010), H1N1pdm09 (2011), B (2012), and H3N2 (2012), respectively. Infection with H1N1pdm09 in 2009-2010 and H3N2 in 2010 was associated with protection against infection with subsequent epidemics of the same subtype in 2011 and 2012, respectively, but we found no evidence of heterotypic or heterosubtypic protection against infection. CONCLUSIONS: We identified substantial incidence of influenza virus infections in children in Hong Kong in 5 major epidemics over a 3-year period, and evidence of homosubtypic but not heterosubtypic protection following infection. CLINICAL TRIALS REGISTRATION: NCT00792051.

Clinical profile analysis of SARS-CoV-2 community infections during periods with omicron BA.2, BA.4/5, and XBB dominance in Hong Kong: a prospective cohort study.

BACKGROUND: Existing studies on SARS-CoV-2 infection have mainly focused on severe clinical outcomes; understanding of the clinical severity profile of general community infections is poor. We aimed to assess and compare the clinical profiles of infections with SARS-CoV-2 omicron (B.1.1.529) subvariants in a representative community cohort in Hong Kong during periods of BA.2, BA.4/5, and XBB dominance. METHODS: In this prospective cohort study in Hong Kong, a representative community cohort of individuals aged at least 5 years were recruited by random-digit dialling and underwent weekly rapid antigen testing for SARS-CoV-2, irrespective of symptoms, during three periods from March 1, 2022, to Oct 31, 2023, in which the BA.2, BA.4/5, or XBB subvariants were dominant. We analysed the likelihood of symptoms, as well as the patterns, severity, and duration of symptoms and their associations with participant demographics and vaccination and infection histories. FINDINGS: 1126 (11·0%) of 10 279 participants in the BA.2 period, 830 (6·6%) of 12 588 in the BA.4/5 period, and 633 (11·1%) of 5690 during the XBB period tested positive for SARS-CoV-2 infection on rapid antigen tests. Community infections were generally mild, with asymptomatic infections comprising 22·0-25·0% of infections. No hospitalisations or deaths occurred as a direct result of SARS-CoV-2 infection during the study period. Compared with children aged 5-17 years, a higher likelihood of being symptomatic on infection was found for adults aged 18-59 years during the period of BA.2 dominance and adults aged 60 years or older during XBB dominance. Most (>90·0%) participants with symptomatic infections reported respiratory and systemic symptoms. Up-to-date vaccination with a regimen containing the BNT162b2 vaccine, compared with those without an up-to-date vaccine, was associated with a reduced likelihood of symptoms on infection during the period of BA.2 dominance and of severe symptoms causing substantial disturbance to daily life (grade 3 symptoms) during periods of BA.2 and BA.4/5 dominance, whereas no association was observed during the period of XBB dominance. Previous SARS-CoV-2 infection was associated with a reduced likelihood of symptoms on infection during BA.4/5 and XBB dominance and of severe symptoms during XBB dominance. Reports of severe symptoms increased over the three periods, from 236 (27·7%) of 852 symptomatic participants during BA.2 dominance to 176 (37·1%) of 475 during XBB dominance. The duration of symptoms was longest in the BA.2 period (median 10·0 days [95% CI 9·0-10·0]) and similar in the other two periods (8·0 [8·0-9·0] during BA.4/5 dominance and 8·0 [8·0-9·0] during XBB dominance). A symptom duration of 60 days or longer was reported only during the period of BA.2 dominance, in six (0·7%) of 824 infections. INTERPRETATION: SARS-CoV-2 infections were generally mild, but not increasingly so, along the evolution of omicron subvariants in this highly vaccinated population. About a third of participants with symptomatic infections reported that the symptoms severely affected daily life even if they were not admitted to hospital, resulting in morbidity, absence from work or school due to illness, productivity loss, and increased medicoeconomic burden. A gradual reduction in the association of vaccines and increase in the association of previous infection with the symptom profile, possibly reflecting the effects of immune escape and waning, were observed over the study period. FUNDING: Henry Fok Foundation and Hong Kong Health Bureau.

Parental vaccine hesitancy and influenza vaccine type preferences during and after the COVID-19 Pandemic.

BACKGROUND: Seasonal influenza vaccine (SIV) greatly reduces disease burden among school-aged children, yet parental vaccine hesitancy remains a persistent challenge. Two types of SIV are available for children in Hong Kong and other locations: inactivated influenza vaccine (IIV), administered through intramuscular injection, and live attenuated influenza vaccine (LAIV), administered via nasal spray. We aimed to understand how vaccine hesitancy shaped parental preference for LAIV versus IIV, particularly amidst important public health events, such as the COVID-19 pandemic and the massive rollout of COVID-19 vaccination campaigns. METHODS: We employed a concurrent mixed-methods design. The quantitative part involves longitudinal surveys spanning three years, from pre-pandemic to post-pandemic periods, tracking parental vaccine hesitancy and preference for SIV types. The qualitative part involves 48 in-depth interviews, providing insights into parental preference for SIV types, underlying reasons, and related values. RESULTS: Our quantitative analyses show an overall increase in parental vaccine hesitancy and preference for LAIV over IIV after the onset of the COVID-19 pandemic and especially after the rollout of the COVID-19 vaccination campaign. Further logistic regression modelling based on the cohort data shows that higher vaccine hesitancy, coupled with the COVID-19 vaccination campaign rollout, predicts a greater preference for LAIV over IIV. The qualitative analysis complements these results, highlighting that LAIV's non-invasive nature aligns with parental values of prioritizing natural immunity and concerns about overmedication, leading to a more acceptable attitude towards LAIV. CONCLUSIONS: Leveraging the higher acceptability of LAIV compared to IIV among parents with high vaccine hesitancy could promote childhood vaccination uptake.

We examined how parents' concerns about vaccines and major public health events affected their preference for different types of seasonal influenza vaccines for children. Currently, children can receive either an injected vaccine or a nasal-spray vaccine. We tracked parental vaccine hesitancy and their preferences for different types of vaccines over three years covering a period before the COVID-19 pandemic and a period during the pandemic. Parents became more hesitant about seasonal influenza vaccines for children after the start of the COVID-19 pandemic and the rollout of COVID-19 vaccines. Higher vaccine hesitancy and the rollout of COVID-19 vaccines predicted a greater preference for nasal-spray vaccines for children among parents. Parents preferred the non-invasive nature of the nasal-spray vaccines and were concerned about overmedication, particularly vaccines that were administered via injection. We suggest that the nasal-spray vaccines could be one option offered to address high parental vaccine hesitancy.

Comparative epidemiology of pandemic and seasonal influenza A in households.

BACKGROUND: There are few data on the comparative epidemiology and virology of the pandemic 2009 influenza A (H1N1) virus and cocirculating seasonal influenza A viruses in community settings. METHODS: We recruited 348 index patients with acute respiratory illness from 14 outpatient clinics in Hong Kong in July and August 2009. We then prospectively followed household members of 99 patients who tested positive for influenza A virus on rapid diagnostic testing. We collected nasal and throat swabs from all household members at three home visits within 7 days for testing by means of quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay and viral culture. Using hemagglutination-inhibition and viral-neutralization assays, we tested baseline and convalescent serum samples from a subgroup of patients for antibody responses to the pandemic and seasonal influenza A viruses. RESULTS: Secondary attack rates (as confirmed on RT-PCR assay) among household contacts of index patients were similar for the pandemic influenza virus (8%; 95% confidence interval [CI], 3 to 14) and seasonal influenza viruses (9%; 95% CI, 5 to 15). The patterns of viral shedding and the course of illness among index patients were also similar for the pandemic and seasonal influenza viruses. In a subgroup of patients for whom baseline and convalescent serum samples were available, 36% of household contacts who had serologic evidence of pandemic influenza virus infection did not shed detectable virus or report illness. CONCLUSIONS: Pandemic 2009 H1N1 virus has characteristics that are broadly similar to those of seasonal influenza A viruses in terms of rates of viral shedding, clinical illness, and transmissibility in the household setting.

Effectiveness of BNT162b2 and CoronaVac COVID-19 vaccination against asymptomatic and symptomatic infection of SARS-CoV-2 omicron BA.2 in Hong Kong: a prospective cohort study.

BACKGROUND: COVID-19 vaccines provide protection against symptomatic infection that might require medical attention and against severe outcomes; however, there is a paucity of evidence regarding the effectiveness of the BNT162b2 and CoronaVac vaccines and their booster regimens against asymptomatic or mild omicron infections in the community. We aimed to measure the effectiveness of BNT162b2 and CoronaVac vaccines against asymptomatic and symptomatic SARS-CoV-2 omicron infections, during a period of omicron BA.2 predominance in Hong Kong. METHODS: In this prospective cohort study in a population that was generally infection-naive before the large omicron BA.2 wave between January and late May, 2022, we established a public health surveillance platform to monitor the evolving activity of SARS-CoV-2 infections in the community. We recruited a cohort of individuals aged 5 years and older between March 1 and March 7, 2022, from the general population. Individuals were enrolled from all 18 districts of Hong Kong, according to a predefined age-stratified quota, primarily by random digit dialing (generating suitable eight-digit local telephone numbers by randomly picking sets of the first four digits from a sampling frame, and randomly generating the last four digits), and supplemented by our existing cohorts (which included cohorts for studying influenza vaccination from school-based vaccination programmes and cohorts for SARS-CoV-2 seroprevalence from the community), to ensure representativeness of the population in Hong Kong. Participants did weekly rapid antigen testing with a self-collected pooled nasal and throat swab, regardless of symptom and exposure status, from March 1 to April 15, 2022. Individuals reporting a history of SARS-CoV-2 infection confirmed by laboratory PCR testing before enrolment were excluded from the vaccine effectiveness analysis to avoid potential bias due to infection-induced immunity. The primary outcomes of the study were the incidence of SARS-CoV-2 infection, including asymptomatic and symptomatic infections, and the vaccine effectiveness of BNT162b2 and CoronaVac vaccines. The effectiveness of one, two, and three doses of vaccination was estimated with a Cox proportional hazards regression model with time-dependent covariates, allowing for changes in vaccination status over time, after adjustment for demographic factors and pre-existing medical conditions. FINDINGS: Of the 8636 individuals included in the analysis, 7233 (84%) received at least two doses of vaccine, 3993 (46%) received booster doses, and 903 (10%) reported SARS-CoV-2 infection. Among these infections 589 (65·2%) were symptomatic and 314 (34·8%) were asymptomatic at the time of testing. Statistically significant protection against asymptomatic and symptomatic SARS-CoV-2 omicron infection was found only for those who received a BNT162b2 or CoronaVac booster dose, with a vaccine effectiveness of 41·4% (23·2 to 55·2; p=0·0001) and 32·4% (9·0 to 49·8; p=0·0098), respectively. The vaccine effectiveness of BNT162b2 and CoronaVac boosters was further increased to 50·9% (95% CI 31·0-65·0; p<0·0001) and 41·6% (15·0-59·8; p=0·0049), respectively, for symptomatic omicron infections. A similar pattern of vaccine effectiveness (55·8%, 22·9-74·6; p=0·0040) was also conferred after receipt of a BNT162b2 booster by individuals who received a CoronaVac primary vaccination series. INTERPRETATION: Two doses of either vaccine did not provide significant protection against COVID-19 infection. However, receipt of a BNT162b2 booster or CoronaVac booster was associated with a significantly lower risk of omicron BA.2 infection and symptomatic infection. Our findings confirm the effectiveness of booster doses to protect against mild and asymptomatic infection. FUNDING: Henry Fok Foundation and Hong Kong Health Bureau.

Protective efficacy against pandemic influenza of seasonal influenza vaccination in children in Hong Kong: a randomized controlled trial.

BACKGROUND: The efficacy of seasonal influenza vaccination against 2009 pandemic influenza A(H1N1) remains unclear. METHODS: One child aged 6-17 years in each of 796 households was randomized to receive 2009-2010 seasonal trivalent inactivated influenza vaccine (TIV) or saline placebo between August 2009 and February 2010. Households were followed up with serology, symptom diaries, and collection of respiratory specimens during illnesses. The primary outcomes were influenza infection confirmed by reverse-transcription polymerase chain reaction (RT-PCR) or a ≥4-fold rise in serum antibody titer measured by hemagglutination inhibition assay. RESULTS: Receipt of TIV led to 8-13-fold mean geometric rises in antibody titers against seasonal A and B viruses, but only 1.5-fold mean geometric rises against the pandemic A(H1N1) virus that was not included in the vaccine. Children who received TIV had a reduced risk of seasonal influenza B confirmed by RT-PCR, with a vaccine efficacy estimate of 66% (95% confidence interval [CI], 31%-83%). Children who received TIV also a had reduced risk of pandemic influenza A(H1N1) indicated by serology, with a vaccine efficacy estimate of 47% (95% CI, 15%-67%). CONCLUSIONS: Seasonal TIV prevented pandemic influenza A(H1N1) and influenza B infections in children. Pandemic A(H1N1) circulated at the time of vaccination and for a short time afterward with no substantial seasonal influenza activity during that period. The potential mechanism for seasonal TIV to provide protection, possibly short lived, for children against pandemic A(H1N1) infection despite poor cross-reactive serologic response deserves further investigation. Clinical Trials Registration. NCT00792051.

Performance of saline and water gargling for SARS-CoV-2 reverse transcriptase PCR testing: a systematic review and meta-analysis.

The performance of gargling for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase (RT)-PCR testing has not been previously reviewed. This review systematically assessed the performance of saline and water gargling for SARS-CoV-2 RT-PCR testing in the settings of diagnosing and monitoring viral shedding.We included original studies comparing the performance of gargling and (oropharyngeal-)nasopharyngeal swabs for SARS-CoV-2 RT-PCR testing. Studies conducted in either suspected individuals or confirmed cases were included and analysed separately. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were examined using random-effects models.Gargles achieved a high overall sensitivity (91%), specificity (97%), PPV (95%) and NPV (91%) for SARS-CoV-2 RT-PCR testing. Studies using saline gargle and water gargle have an overall sensitivity of 97% and 86%, respectively. The sensitivity values were largely maintained for saline and water gargling on stratified analysis, for both diagnosis (96% and 92%) and viral shedding monitoring (98% and 78%). A higher sensitivity was also reported by studies using sterile saline (100%), a smaller amount of gargling solution (92% versus 87%) and a longer gargling duration (95% versus 86%).Our results supported the use of gargling as a sampling approach for SARS-CoV-2 RT-PCR testing, which achieved a high sensitivity for both diagnosis and viral shedding monitoring purposes. Further investigation on the comparative performance of different gargling mediums is needed to draw a definitive conclusion.

Indirect Protection from Vaccinating Children against Influenza A Virus Infection in Households.

Influenza vaccination is an important intervention to prevent influenza virus infection. Our previous analysis suggested that indirect protection is limited in an influenza B epidemic in Hong Kong. We further analyzed six influenza A epidemics to determine such potential. We applied a statistical model to estimate household transmission dynamics in the 3 influenza A(H3N2) and 3 pandemic influenza A(H1N1) epidemics. Then, we estimated the reduction in infection risk among unvaccinated household members when all children in households are vaccinated, with different assumptions on vaccine efficacy (VE). In the optimal scenario that VE was 70%, the reduction to the total probability of infection was only marginal, with relative probabilities ranged from 0.91-0.94 when all children in households were vaccinated because community was by far the main source of infection during the six epidemics in our study. The proportion of cases attributed to household transmission was 10% (95% CrI: 7%, 13%). Individual influenza vaccination is important even when other household members are vaccinated, given the degree of indirect protection is small.

Reconstructing antibody dynamics to estimate the risk of influenza virus infection.

For >70 years, a 4-fold or greater rise in antibody titer has been used to confirm influenza virus infections in paired sera, despite recognition that this heuristic can lack sensitivity. Here we analyze with a novel Bayesian model a large cohort of 2353 individuals followed for up to 5 years in Hong Kong to characterize influenza antibody dynamics and develop an algorithm to improve the identification of influenza virus infections. After infection, we estimate that hemagglutination-inhibiting (HAI) titers were boosted by 16-fold on average and subsequently decrease by 14% per year. In six epidemics, the infection risks for adults were 3%-19% while the infection risks for children were 1.6-4.4 times higher than that of younger adults. Every two-fold increase in pre-epidemic HAI titer was associated with 19%-58% protection against infection. Our inferential framework clarifies the contributions of age and pre-epidemic HAI titers to characterize individual infection risk.

A Mixed-Methods Study to Evaluate Elementary School Staff's Acceptability, Delivery Challenges, and Communication Regarding the Implementation of School-Located Influenza Vaccination Program in Hong Kong.

This was a mixed-methods study comprising a questionnaire-based survey, a qualitative study, and analysis of school newsletters to evaluate elementary school staff's acceptability, delivery challenges and communication about school-located influenza vaccination program (SIVP) in Hong Kong. We found that school staff with lower intention to implement SIVP perceived greater logistical difficulties in arranging SIVP. Challenges regarding program delivery included schools' limited infrastructure, the burden of paperwork, the fear of being overwhelmed by multiple school-based vaccination schedules, lacking confidence in communicating with parents about influenza vaccines, and the difficulties in managing vaccination-related anxiety among children with intellectual disability. School staff were generally passive in communicating with parents and students about influenza vaccines. We also found that schools may use the school newsletters as a substitute of the formal informed consent forms. Good partnerships among government, service providers and schools should be established to minimize the burden of paperwork for school staff, facilitate early planning of SIVP, and support schools with limited infrastructure and the vaccination of children with intellectual disabilities. Training is needed to enhance school staff's confidence in communicating with parents and students about influenza vaccines and improve information delivery to support parents' informed decisions for children's vaccination.

Diagnostic performance of different sampling approaches for SARS-CoV-2 RT-PCR testing: a systematic review and meta-analysis.

BACKGROUND: The comparative performance of different clinical sampling methods for diagnosis of SARS-CoV-2 infection by RT-PCR among populations with suspected infection remains unclear. This meta-analysis aims to systematically compare the diagnostic performance of different clinical specimen collection methods. METHODS: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, MEDLINE, Web of Science, medRxiv, bioRxiv, SSRN, and Research Square from Jan 1, 2000, to Nov 16, 2020. We included original clinical studies that examined the performance of nasopharyngeal swabs and any additional respiratory specimens for the diagnosis of SARS-CoV-2 infection among individuals presenting in ambulatory care. Studies without data on paired samples, or those that only examined different samples from confirmed SARS-CoV-2 cases were not useful for examining diagnostic performance of a test and were excluded. Diagnostic performance, including sensitivity, specificity, positive predictive value, and negative predictive value, was examined using random effects models and double arcsine transformation. FINDINGS: Of the 5577 studies identified in our search, 23 studies including 7973 participants with 16 762 respiratory samples were included. Respiratory specimens examined in these studies included 7973 nasopharyngeal swabs, 1622 nasal swabs, 6110 saliva samples, 338 throat swabs, and 719 pooled nasal and throat swabs. Using nasopharyngeal swabs as the gold standard, pooled nasal and throat swabs gave the highest sensitivity of 97% (95% CI 93-100), whereas lower sensitivities were achieved by saliva (85%, 75-93) and nasal swabs (86%, 77-93) and a much lower sensitivity by throat swabs (68%, 35-94). A comparably high positive predictive value was obtained by pooled nasal and throat (97%, 90-100) and nasal swabs (96%, 87-100) and a slightly lower positive predictive value by saliva (93%, 88-97). Throat swabs have the lowest positive predictive value of 75% (95% CI 45-96). Comparably high specificities (range 97-99%) and negative predictive value (range 95-99%) were observed among different clinical specimens. Comparison between health-care-worker collection and self-collection for pooled nasal and throat swabs and nasal swabs showed comparable diagnostic performance. No significant heterogeneity was observed in the analysis of pooled nasal and throat swabs and throat swabs, whereas moderate to substantial heterogeneity (I2 ≥30%) was observed in studies on saliva and nasal swabs. INTERPRETATION: Our review suggests that, compared with the gold standard of nasopharyngeal swabs, pooled nasal and throat swabs offered the best diagnostic performance of the alternative sampling approaches for diagnosis of SARS-CoV-2 infection in ambulatory care. Saliva and nasal swabs gave comparable and very good diagnostic performance and are clinically acceptable alternative specimen collection methods. Throat swabs gave a much lower sensitivity and positive predictive value and should not be recommended. Self-collection for pooled nasal and throat swabs and nasal swabs was not associated with any significant impairment of diagnostic accuracy. Our results also provide a useful reference framework for the proper interpretation of SARS-CoV-2 testing results using different clinical specimens. FUNDING: Hong Kong Research Grants Council.

Testing an integrative theory of health behavioural change for predicting seasonal influenza vaccination uptake among healthcare workers.

BACKGROUND: Although annual seasonal influenza vaccination is recommended for healthcare personnel (HCPs), their vaccination uptake has been suboptimal. This study aimed to examine the psychosocial determinants of influenza vaccination among HCPs in Hong Kong using a longitudinal study design based on behavioral change theories. METHODS: Participants were invited to complete a baseline survey before the 2017/18 influenza vaccination campaign to measure their baseline perceptions and vaccination intention, and followed up for 9 months to measure actual vaccination uptake. The survey used a theoretical framework combining the Health Belief Model and Theory of Planned Behaviour with extended psychosocial factors for predicting HCPs' vaccination uptake. Structural equation modelling was used to test the theoretical model and estimate path coefficients (ß) to infer associations of psychosocial factors with HCPs' influenza vaccination uptake. RESULTS: Of the 845 participants who completed follow-up, 43.0% indicated intending to take vaccination and 30.8% reported actual receipt of the vaccination. The structural equation modeling analysis showed that positive attitude towards influenza vaccination (ß = 0.69), greater perceived susceptibility to influenza virus infection (ß = 0.34), greater anticipated regret for not vaccinating (ß = 0.31), and more cues to action (ß = 0.29) were significantly associated with higher vaccination intention which directly predicted greater vaccination uptake (ß = 0.82). Norms were found to have an indirect association with vaccination intention through the mediation of attitude towards influenza vaccination (ß = 0.63). Self-efficacy was significantly associated with actual receipt of influenza vaccination (ß = 0.13) but not vaccination intention. The structural equation model explained 84.7% and 69.6% of the variance, respectively, in HCPs' intention to receive and actual receipt of influenza vaccination. CONCLUSIONS: Attitude towards influenza vaccination was the strongest predictor of HCPs' intention and actual receipt of influenza vaccination. Social norm approach may be an intervention strategy to shape HCPs' attitude towards influenza vaccination and their subsequent decision-making for influenza vaccination.

Indirect protection from vaccinating children against influenza in households.

Vaccination is an important intervention to prevent influenza virus infection, but indirect protection of household members of vaccinees is not fully known. Here, we analyze a cluster household randomized controlled trial, with one child in each household randomized to receive influenza vaccine or placebo, for an influenza B epidemic in Hong Kong. We apply statistical models to estimate household transmission dynamics and quantify the direct and indirect protection of vaccination. Direct vaccine efficacy was 71%. The infection probability of unvaccinated household members in vaccinated households was only 5% lower than in control households, because only 10% of infections are attributed to household transmission. Even when that proportion rises to 30% and all children are vaccinated, we predict that the infection probability for unvaccinated household members would only be reduced by 20%. This suggests that benefits of individual vaccination remain important even when other household members are vaccinated.