Publications by authors named "Hau Chi So"

12 Publications

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

Lancet Infect Dis 2021 Apr 12. Epub 2021 Apr 12.

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address:

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 (I ≥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.
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http://dx.doi.org/10.1016/S1473-3099(21)00146-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041361PMC
April 2021

Public perception and performance of different sampling approaches for the diagnosis of COVID-19.

Influenza Other Respir Viruses 2021 05 4;15(3):420-422. Epub 2021 Jan 4.

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

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http://dx.doi.org/10.1111/irv.12834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051699PMC
May 2021

Comparative Reactogenicity of Enhanced Influenza Vaccines in Older Adults.

J Infect Dis 2020 09;222(8):1383-1391

Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

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.
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http://dx.doi.org/10.1093/infdis/jiaa255DOI Listing
September 2020

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

J Infect Dis 2020 09;222(8):1329-1333

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.

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.
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http://dx.doi.org/10.1093/infdis/jiaa114DOI Listing
September 2020

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

Clin Infect Dis 2020 10;71(7):1704-1714

Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

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.
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http://dx.doi.org/10.1093/cid/ciz1034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289658PMC
October 2020

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

Vaccine 2020 01 24;38(3):690-698. Epub 2019 Oct 24.

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region; Division of Behavioural Sciences, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.

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 (β) 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 (β = 0.69), greater perceived susceptibility to influenza virus infection (β = 0.34), greater anticipated regret for not vaccinating (β = 0.31), and more cues to action (β = 0.29) were significantly associated with higher vaccination intention which directly predicted greater vaccination uptake (β = 0.82). Norms were found to have an indirect association with vaccination intention through the mediation of attitude towards influenza vaccination (β = 0.63). Self-efficacy was significantly associated with actual receipt of influenza vaccination (β = 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.
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http://dx.doi.org/10.1016/j.vaccine.2019.10.041DOI Listing
January 2020

Indirect protection from vaccinating children against influenza in households.

Nat Commun 2019 01 10;10(1):106. Epub 2019 Jan 10.

Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, 25-28 Rue du Docteur Roux, 75015, Paris, France.

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.
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http://dx.doi.org/10.1038/s41467-018-08036-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328591PMC
January 2019

A Smart Card-Based Electronic School Absenteeism System for Influenza-Like Illness Surveillance in Hong Kong: Design, Implementation, and Feasibility Assessment.

JMIR Public Health Surveill 2017 Oct 6;3(4):e67. Epub 2017 Oct 6.

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China (Hong Kong).

Background: School-aged children have the highest incidence of respiratory virus infections each year, and transmission of respiratory viruses such as influenza virus can be a major concern in school settings. School absenteeism data have been employed as a component of influenza surveillance systems in some locations. Data timeliness and system acceptance remain as key determinants affecting the usefulness of a prospective surveillance system.

Objective: The aim of this study was to assess the feasibility of implementing an electronic school absenteeism surveillance system using smart card-based technology for influenza-like illness (ILI) surveillance among a representative network of local primary and secondary schools in Hong Kong.

Methods: We designed and implemented a surveillance system according to the Protocol for a Standardized information infrastructure for Pandemic and Emerging infectious disease Response (PROSPER). We employed an existing smart card-based education and school administration platform for data capture, customized the user interface, and used additional back end systems built for other downstream surveillance steps. We invited local schools to participate and collected absenteeism data by the implemented system. We compared temporal trend of the absenteeism data with data from existing community sentinel and laboratory surveillance data.

Results: We designed and implemented an ILI surveillance system utilizing smart card-based attendance tracking approach for data capture. We implemented the surveillance system in a total of 107 schools (including 66 primary schools and 41 secondary schools), covering a total of 75,052 children. The system successfully captured information on absences for 2 consecutive academic years (2012-2013 and 2013-2014). The absenteeism data we collected from the system reflected ILI activity in the community, with an upsurge in disease activity detected up to 1 to 2 weeks preceding other existing surveillance systems.

Conclusions: We designed and implemented a novel smart card technology-based school absenteeism surveillance system. Our study demonstrated the feasibility of building a large-scale surveillance system riding on a routinely adopted data collection approach and the use of simple system enhancement to minimize workload implication and enhance system acceptability. Data from this system have potential value in supplementing existing sentinel influenza surveillance for situational awareness of influenza activity in the community.
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http://dx.doi.org/10.2196/publichealth.6810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650675PMC
October 2017

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

BMC Infect Dis 2015 Dec 29;15:586. Epub 2015 Dec 29.

Hong Kong Centre of Occupational Medicine, Hong Kong Special Administrative Region, Hong Kong, China.

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.
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http://dx.doi.org/10.1186/s12879-015-1316-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4696217PMC
December 2015

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

Clin Infect Dis 2014 Aug 13;59(4):517-24. Epub 2014 May 13.

Division of Community Medicine and Public Health Practice, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.

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.
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http://dx.doi.org/10.1093/cid/ciu356DOI Listing
August 2014

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

Clin Infect Dis 2012 Sep 5;55(5):695-702. Epub 2012 Jun 5.

School of Public Health.

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.
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http://dx.doi.org/10.1093/cid/cis518DOI Listing
September 2012

Comparative epidemiology of pandemic and seasonal influenza A in households.

N Engl J Med 2010 Jun;362(23):2175-2184

Infectious Disease Epidemiology Group, School of Public Health (B.J.C., V.J.F., L.L.H.L., H.C.S., R.O.P.F., G.M.L.), and the Department of Microbiology (K.H.C., E.S.K.M., J.S.M.P.), Li Ka Shing Faculty of Medicine, University of Hong Kong; Hospital Authority, Government of the Hong Kong Special Administrative Region (A.S.K.K., C.-W.C., W.W.S.T., H.-Y.N., D.W.S.C.); St. Paul's Hospital (P.W.Y.L.); St. Teresa's Hospital (M.-C.C.); and HKU-Pasteur Research Centre (J.S.M.P.) - all in Hong Kong.

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.
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http://dx.doi.org/10.1056/NEJMoa0911530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070281PMC
June 2010