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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. Relevance of indirect protection of household members of vaccinees is unclear. Here, Tsang et al. quantify the direct and indirect protection of vaccination in a randomized controlled trial and show that benefits of individual vaccination remain important even when other household members are vaccinated.

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. 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. 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. 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. Hong Kong Research Grants Council.

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. Serological classification of influenza infection has classically been based on a four-fold or higher increase in antibody levels, but this approach may not be optimal. Here, the authors develop a Bayesian model to improve identification of infections in serological samples by accounting for individual antibody dynamics.

Pandemic 2009 influenza A (H1N1) virus has caused substantial disease around the world during the past year. In this study from Hong Kong, investigators show that the pandemic and seasonal influenza A viruses behave in a similar manner with respect to the pattern of illness, viral shedding, and secondary attack rates. In this study from Hong Kong, investigators show that the pandemic and seasonal influenza A viruses behave in a similar manner with respect to the pattern of illness, viral shedding, and secondary attack rates. Households are thought to play a major role in the community spread of influenza virus during annual epidemics and occasional pandemics. 1 – 4 As the pandemic 2009 influenza A (H1N1) virus (hereafter called pandemic virus) spread across the world, many countries implemented mitigation policies, including the recommendation that persons with confirmed or suspected infection be isolated at home. 5 – 7 The literature contains few data on viral-shedding patterns associated with naturally acquired influenza virus infections in community settings. Although data have been published on humoral antibody responses to the pandemic virus after vaccination against seasonal influenza, 8 little is known about antibody responses . . .

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. Plain language summary 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. Yuan et. al examine how parental vaccine hesitancy and the rollout of COVID-19 vaccination programs affected preferences for the type of childhood seasonal influenza vaccines. Results provide insights for future vaccination programs by examining reasoning behind parental decisions.

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.

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.

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.

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.