The global spread of viruses highlights the need for timely and effective genomic surveillance to detect new variants and inform rapid public health responses. However, high costs and uneven sequencing capacity hinder equitable global implementation. Surveillance focused on international travelers at major travel hubs has been proposed as a way to complement robust local surveillance, but its potential benefits have not been fully quantified. Here, we develop and calibrate a multiple-strain metapopulation model of global SARS-CoV-2 transmission using extensive epidemiological, phylogenetic, and high-resolution air travel data. Retrospective analyses of the Omicron BA.1/BA.2 emergence and forward simulations for hypothetical novel variants show that targeted enhancement of traveler surveillance at key hubs can shorten variant detection delays, with reduced total surveillance efforts. Practical "non-disruptive" strategies, such as prioritizing a small number of highly connected hubs, consistently outperformed baseline approaches and remained effective across a range of variant transmissibility and vaccine effectiveness scenarios. These results provide a quantitative framework for strengthening global genomic surveillance through targeted, complementary strategies that preserve local capacity while improving preparedness for future pandemics.

Understanding host factors driving asymptomatic versus severe disease outcomes is of key importance if we are to control emerging and re-emerging viral infections. HLA-B*15:01 has been associated with asymptomatic SARS-CoV-2 infection in nonhospitalized individuals of European ancestry, with protective immunity attributed to preexisting cross-reactive CD8+ T-cells directed against HLA-B*15:01-restricted Spike-derived S919-927 peptide (B15/S919+CD8+ T-cells). However, fundamental questions remained on the abundance and clonotypic nature of CD8+ T-cell responses in HLA-B*15:01-positive patients who succumbed to life-threatening COVID-19. Here, we analyzed B15/S919+CD8+ T-cell responses in COVID-19 patients from independent HLA-typed COVID-19 patient cohorts across three continents, Australia, Asia and Europe. We assessed B15/S919+CD8+ T-cells in COVID-19 patients across disease outcomes ranging from asymptomatic to hospitalized critical illness. We found that severe/critical COVID-19 patients mounted B15/S919+CD8+ T-cell responses lacking a highly expanded key public B15/S919+CD8+ T-cell receptor (TCR; TRAV9-2/TRBV7-2) which recurred across multiple individuals in COVID-19 patients with a mild disease. Instead, B15/S919+CD8+ T-cell responses in life-threatening disease had a prevalence of an alternate TCR clonotypic motif (TRAV38-2/DV8/TRBV20-1), potentially contributing, at least in part, to why B15/S919+CD8+ T-cells in severe COVID-19 patients were less protective. Interestingly, the frequency, memory phenotype, and activation profiles of circulating B15/S919+CD8+ T-cells did not differ across disease severity. Moreover, B15/S919+CD8+ T-cells were better maintained into convalescence compared to other SARS-CoV-2-specificities. Our study thus provides evidence on the differential nature of the TCR clonal repertoire in 22.37% of HLA-B*15:01-positive COVID-19 patients who developed severe or critical disease in our cohorts, comparing to HLA-B*15:01-expressing individuals with mild COVID-19.

Vaccine hesitancy seriously compromised the COVID-19 vaccine roll-out across the Western Pacific with limited evidence-based recommendations for diverse populations across the region. This study investigates the profile of the vaccine-hesitant populations by using fixed-effect latent class analysis and multi-country survey data collected in 12 countries in 2021 and 2022: Cambodia, Viet Nam, Lao PDR, Japan, Republic of Korea, Malaysia, Philippines, Mongolia, Fiji, Solomon Islands, Tonga and Vanuatu. The analysis identified 9 latent classes: Stay-at-home mothers, High-school-educated employees, High-school-educated older adults, High-school-educated young adults, University-educated employees, University-educated older adults, University-educated young adults, Unemployed, Non-compliant employees. The probabilities of COVID-19 vaccine acceptance and booster uptake were significantly lower in most of these latent classes, compared to University-educated older adults, as the reference group. While each country had unique compositions of latent classes among vaccine-hesitant people, there were also some shared risk groups, such as High-school-educated employees and High-school-educated young adults, across the countries. The study findings demonstrate the benefits of subgroup analysis in unpacking the complex interplay of characteristics within vaccine-hesitant populations, highlighting the need for customised strategies tailored to each country’s unique profile of vaccine hesitancy.

Objectives: This study aimed to assess the long-term persistence of neutralizing antibodies (nAb) titres and seroprotection proportions after the fourth and fifth doses of inactivated polio vaccine (IPV). Methods: Serum samples from 299 children in Hong Kong were collected and used to estimate the persistence of nAb titres and seroprotection proportions by neutralisation test. Results: The mean nAb titres against poliovirus types 1, 2, and 3 (PV1, PV2, and PV3) 1 month after receiving the fourth dose of IPV at 19 months of age were 2068 (95% credible interval, 1517-2864); 4705 (3439-6436); and 2758 (1894-4086); respectively, but declined substantially in 4 years to 268 (222 -325), 751 (630-90 0), and 411 (323-521), respectively. Administration of the fifth dose of IPV restored nAb titres among children aged 6 to 7 years, and the decline in nAb titres was slightly slower with the estimated mean titres of 355 (272-462), 538 (427-681), and 548 (378-786) against PV1, PV2, and PV3 at 4 years post the fifth dose. We estimated that the proportion of children who were seroprotected against PV1, PV2, and PV3 would drop below 90%: (i) 8.2, 10.8, and 8.7 years after the fourth dose; and (ii) 11.6, 11.2, and 11.0 years after the fifth dose. Discussion: The results revealed the immuno-persistence after the fourth and fifth doses of IPV and highlighted the importance of completing immunization series to ensure high vaccination coverage, particularly among children in the developing countries affected by the COVID-19 pandemic. Kathy Leung, Clin Microbiol Infect 2025;31:625 (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

Sustainable Development Goal (SDG) adopted in 2015 aim to reduce inequalities and achieve universal health coverage, including access to essential vaccines for all. Using data from WHO, the Vaccine Confidence Project™, World Bank, and UNDP, we analyzed between-country inequalities in coverage of four vaccines (DTP1, DTP3, MCV1, and POL3), vaccine stock-outs, and vaccine confidence. Economic- and education-related inequalities in coverage (measured by the concentration index) declined from 2015 to 2019, increased in 2020, peaked in 2021, and have declined again since 2022. Inequalities increased continuously in the Region of the Americas. Over 2015–2022, 94 countries/territories reported at least one national level DTP-containing vaccine stock-out. Countries/territories with higher income or education attainment showed lower vaccine confidence. Our study underscores the decrease of inequalities in vaccination coverage following the SDG adoption in most regions, and emphasizes the need to address vaccine stock-outs and strength the vaccine confidence.

BACKGROUND:In Japan, human papillomavirus (HPV) vaccine uptake has been hindered by public distrust and misinformation. Understanding which message components can effectively influence mothers' vaccine decision-making is critical for restoring confidence and improving coverage. OBJECTIVE:To assess the impact of different message components on mothers' willingness to vaccinate their daughters against HPV. METHODS:This study employed an online 2 × 2 × 2 × 2 between-person factorial randomized controlled trial with a nationally representative sample of 1439 Japanese mothers of daughters aged 11-18. Participants were randomly assigned to view one of 16 digital text-based messages varying by four components: messenger (individual or organization), content (effectiveness or safety), style (storytelling or scientific data), and misinformation (misinformation or factual information). Outcomes were willingness to vaccinate, confidence in vaccine safety and effectiveness, message trust, and concern about HPV-related diseases. Logistic regression and model fit statistics were used to assess the impact of components. RESULTS:Among 1324 mothers analyzed, messages with factual information significantly increased willingness to vaccinate daughters compared to misinformation (25.9 % vs. 11.3 %; OR = 2.75; 95 % CI = 2.02-3.74), while trust was higher for organizational messages (91.6 %; OR = 1.58; 95 % CI = 1.10-2.27). Storytelling messages increased concerns about HPV-related diseases more than scientific data (40.4 % vs. 31.9 %, OR = 1.45; 95 % CI = 1.15-1.82). Although factual information and trusted sources positively influenced attitudes, a single digital message was insufficient to significantly increase vaccination uptake. Furthermore, misinformation reduced confidence in vaccine safety and effectiveness. CONCLUSIONS:Digital messages containing factual information and delivered by organizations positively influence mothers' intentions to vaccinate their daughters against HPV in Japan. These findings support strategies that emphasize trusted sources and factual content while countering misinformation to improve vaccine confidence and uptake. The study was registered at Clinicaltrials.gov (NCT06347627).

Background: The epidemiology and natural history of colorectal cancer (CRC) is poorly understood across many populations, hindering effective disease prevention. We hypothesize that quantitative fecal immunochemical test (FIT) data from CRC screening programs can be used to characterize the prevalence and disease progression of CRC. Methods: We developed an inferential framework to characterize the epidemiology of CRC using quantitative FIT data from 248,692 first-time screenees of the Hong Kong CRC Screening Program during 2016- 2021 (aged 49-77; 56.4% female). Each screenee submitted two fecal samples and was referred for colonoscopy if one or both FIT values exceeded 100 ng/ml (13.1% FIT-positivity). A natural history model, comprising both the conventional adenoma and serrated pathways, was embedded to infer unobserved disease stages in FIT-negative screenees. Findings: We estimated that without screening, 41.1% (95% credible interval = 39.4%-44.0%) of males and 31.0% (29.7%-32.4%) of females would have colorectal neoplastic diseases at age 50. Among them, approximately 7-8% would have advanced colorectal neoplasia (advanced adenoma, serrated lesions, or CRC). The prevalence of advanced neoplasia increases with age, approximately by 0.5% per year after age 50. The annual progression rate to CRC was around 4% for advanced adenoma and 1-2% for serrated lesions. Males with advanced neoplasia generally had higher FIT concentrations than females. In detecting advanced neoplasia, the negative predictive value of FIT was above 99% across all ages, while the positive predictive value was 15-20% at age 50, increasing by around 1% each subsequent year. FIT demonstrates high sensitivity in detecting CRC, ranging from 83% to 98% in both genders. Interpretation: Quantitative FIT-based CRC screening data can be used to effectively characterize the epidemiology and natural history of colorectal cancer. Our novel framework provides a solid foundation for optimizing the effectiveness and cost-effectiveness of screening programs. Funding: Health and Medical Research Fund (HMRF), Hong Kong Special Administrative Region, China.

Conversational artificial intelligence, in the form of chatbots powered by large language models, offers a new approach to facilitating human-like interactions, yet its efficacy in enhancing vaccination uptake remains under-investigated. This study assesses the effectiveness of a vaccine chatbot in improving human papillomavirus (HPV) vaccination among female middle school students aged 12-15 years across diverse socioeconomic settings in China, where HPV vaccination is primarily paid out-of-pocket. A school-based cluster randomized trial was conducted from 18 January to 31 May 2024. The study included 2,671 parents from 180 middle school classes stratified by socioeconomic setting, school and grade level in Shanghai megacity, and urban and rural regions of Anhui Province. Participants were randomly assigned to either the intervention group (90 classes, 1,294 parents), which engaged with the chatbot for two weeks, or the control group (90 classes, 1,377 parents), which received usual care. The primary outcome was the receipt or scheduled appointment of the HPV vaccine for participants' daughters. In intention-to-treat analyses, 7.1% of the intervention group met this outcome versus 1.8% of the control group (P < 0.001) over a two-week intervention period. In addition, there was a statistically significant increase in HPV vaccination-specific consultations with health professionals (49.1% versus 17.6%, P < 0.001), along with enhanced vaccine literacy (P < 0.001) and rumor discernment (P < 0.001) among participants using the chatbot. These findings indicate that the chatbot effectively increased vaccination and improved parental vaccine literacy, although further research is necessary to scale and sustain these gains. Clinical trial registration: NCT06227689.

Data availabilityAll data included in the analyses are available in the main text or supplementary materials.

The SARS-CoV-2 Omicron variant has demonstrated enhanced transmissibility and escape of vaccine-derived immunity. Although first-generation vaccines remain effective against severe disease and death, robust evidence on vaccine effectiveness (VE) against all Omicron infections, irrespective of symptoms, remains sparse. We used a community-wide serosurvey with 5,310 subjects to estimate how vaccination histories modulated risk of infection in infection-naive Hong Kong during a large wave of Omicron BA.2 epidemic in January-July 2022. We estimated that Omicron infected 45% (41-48%) of the local population. Three and four doses of BNT162b2 or CoronaVac were effective against Omicron infection 7 days after vaccination (VE of 48% (95% credible interval 34-64%) and 69% (46-98%) for three and four doses of BNT162b2, respectively; VE of 30% (1-66%) and 56% (6-97%) for three and four doses of CoronaVac, respectively). At 100 days after immunization, VE waned to 26% (7-41%) and 35% (10-71%) for three and four doses of BNT162b2, and to 6% (0-29%) and 11% (0-54%) for three and four doses of CoronaVac. The rapid waning of VE against infection conferred by first-generation vaccines and an increasingly complex viral evolutionary landscape highlight the necessity for rapidly deploying updated vaccines followed by vigilant monitoring of VE.

Wastewater surveillance can leverage its wide coverage, population-based sampling, and high monitoring frequency to capture citywide pandemic trends independent of clinical surveillance. Here we conducted a 9-month daily wastewater surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 12 wastewater treatment plants (WWTPs), covering approximately 80% of the population, to monitor infection dynamics in Hong Kong. We found that the SARS-CoV-2 virus concentration in wastewater was correlated with the daily number of reported cases and reached two pandemic peaks three days earlier during the study period. In addition, two different methods were established to estimate the prevalence/incidence rates from wastewater measurements. The estimated results from wastewater were consistent with findings from two independent citywide clinical surveillance programmes (rapid antigen test (RAT) surveillance and serology surveillance), but higher than the cases number reported by the Centre for Health Protection (CHP) of Hong Kong. Moreover, the effective reproductive number (Rt) was estimated from wastewater measurements to reflect both citywide and regional transmission dynamics. Our findings demonstrate that large-scale intensive wastewater surveillance from WWTPs provides cost-effective and timely public health information, especially when the clinical surveillance is inadequate and costly. This approach also provides insights into pandemic dynamics at higher spatiotemporal resolutions, facilitating the formulation of effective control policies and targeted resource allocation.

BackgroundNovel coronaviruses have emerged and caused major epidemics and pandemics in the past 2 decades, including SARS-CoV-1, MERS-CoV, and SARS-CoV-2, which led to the current COVID-19 pandemic. These coronaviruses are marked by their potential to produce disproportionally large transmission clusters from superspreading events (SSEs). As prompt action is crucial to contain and mitigate SSEs, real-time epidemic size estimation could characterize the transmission heterogeneity and inform timely implementation of control measures. ObjectiveThis study aimed to estimate the epidemic size of SSEs to inform effective surveillance and rapid mitigation responses. MethodsWe developed a statistical framework based on back-calculation to estimate the epidemic size of ongoing coronavirus SSEs. We first validated the framework in simulated scenarios with the epidemiological characteristics of SARS, MERS, and COVID-19 SSEs. As case studies, we retrospectively applied the framework to the Amoy Gardens SARS outbreak in Hong Kong in 2003, a series of nosocomial MERS outbreaks in South Korea in 2015, and 2 COVID-19 outbreaks originating from restaurants in Hong Kong in 2020. ResultsThe accuracy and precision of the estimation of epidemic size of SSEs improved with longer observation time; larger SSE size; and more accurate prior information about the epidemiological characteristics, such as the distribution of the incubation period and the distribution of the onset-to-confirmation delay. By retrospectively applying the framework, we found that the 95% credible interval of the estimates contained the true epidemic size after 37% of cases were reported in the Amoy Garden SARS SSE in Hong Kong, 41% to 62% of cases were observed in the 3 nosocomial MERS SSEs in South Korea, and 76% to 86% of cases were confirmed in the 2 COVID-19 SSEs in Hong Kong. ConclusionsOur framework can be readily integrated into coronavirus surveillance systems to enhance situation awareness of ongoing SSEs.

Massive sequencing of SARS-CoV-2 genomes has urged novel methods that employ existing phylogenies to add new samples efficiently instead of de novo inference. 'TIPars' was developed for such challenge integrating parsimony analysis with pre-computed ancestral sequences. It took about 21 seconds to insert 100 SARS-CoV-2 genomes into a 100k-taxa reference tree using 1.4 gigabytes. Benchmarking on four datasets, TIPars achieved the highest accuracy for phylogenies of moderately similar sequences. For highly similar and divergent scenarios, fully parsimony-based and likelihood-based phylogenetic placement methods performed the best respectively while TIPars was the second best. TIPars accomplished efficient and accurate expansion of phylogenies of both similar and divergent sequences, which would have broad biological applications beyond SARS-CoV-2. TIPars is accessible from https://tipars.hku.hk/ and source codes are available at https://github.com/id-bioinfo/TIPars.

OBJECTIVE:China has a substantial disease burden of cervical cancer. To further understand preventive measures for reducing cervical cancer in China, this study aimed to correlate screening attendance and regular screening with human papillomavirus (HPV) vaccination among Chinese females. METHODS:This prospective questionnaire-based survey recruited Chinese females aged 25 or above in Hong Kong by random digit dialing telephone interviews in 2022. The survey studied women's practice of cervical screening and adherence to regular screening. Variables including HPV vaccination status and attendance of physical check-ups were involved in the questionnaire. Screening uptake and screening adherence were the main outcomes, which were measured as the proportion of women who reported having attended a cervical screening and screened regularly, respectively. RESULTS:Out of 906 valid respondents, the reported cervical screening uptake was over 70% among females aged 30 or above and particularly over 80% among women aged 35-59; however, the uptake was only 46% among those aged 25-29. Adherence to regular screening was 50%-60% across ages 25-59 years and dropped to approximately 40% for women older than 60 years. Both screening uptake and adherence were associated with HPV vaccination, with adjusted odds ratios of 2.37 and 2.23, respectively. A large proportion of regularly screened women may be overscreened for screening more frequently than recommended. CONCLUSION:Responded Chinese females showed good cervical screening uptake but were moderately adherent to regular screening. Policymakers should emphasize the importance of regular screening and the recommended screening frequency by HPV vaccination status for better healthcare resource use.

The wastewater surveillance network successfully established for COVID-19 showed great potential to monitor other infectious viruses, such as norovirus, rotavirus and mpox virus. In this study, we established and validated detection methods for these viruses in wastewater. We developed a supernatant-based method to detect RNA viruses from wastewater samples and applied it to the monthly diarrhea viruses (norovirus genogroup I & II, and rotavirus) surveillance in wastewater treatment plants (WWTPs) at a city-wide level for 16 months. Significant correlations were observed between the diarrhea viruses concentrations in wastewater and detection rates in faecal specimens by clinical surveillance. The highest norovirus concentration in wastewater was obtained in winter, consistent with the seasonal pattern of norovirus outbreak in Hong Kong. Additionally, we established a pellet-based method to monitor DNA viruses in wastewater and detected weak signals for mpox virus in wastewater from a WWTP serving approximately 16,700 people, when the first mpox patient in Hong Kong was admitted to the hospital within the catchment area. Genomic sequencing provided confirmatory evidence for the validity of the results. Our findings emphasized the efficacy of the wastewater surveillance network in WWTPs as a cost-effective tool to track the transmission trend of diarrhea viruses and to provide sensitive detection of novel emerging viruses such as mpox virus in low-prevalence areas. The developed methods and surveillance results provide confidence for establishing robust wastewater surveillance programs to control infectious diseases in the post-pandemic era.

We detected high titers of cross-reactive neuraminidase inhibition antibodies to influenza A(H5N1) virus clade 2.3.4.4b in 96.8% (61/63) of serum samples from healthy adults in Hong Kong in 2020. In contrast, antibodies at low titers were detected in 42% (21/50) of serum samples collected in 2009. Influenza A(H1N1)pdm09 and A(H5N1) titers were correlated.

The unprecedentedly large size of the global SARS-CoV-2 phylogeny makes any computation on the tree difficult. Lineage identification (e.g. the PANGO nomenclature for SARS-CoV-2) and assignment are key to track the virus evolution. It requires annotating clade roots of lineages to unlabeled ancestral nodes in a phylogenetic tree. Then the lineage labels of descendant samples under these clade roots can be inferred to be the corresponding lineages. This is the ancestral lineage annotation problem, and matUtils (a package in pUShER) and PastML are commonly used methods. However, their computational tractability is a challenge and their accuracy needs further exploration in huge SARS-CoV-2 phylogenies. We have developed an efficient and accurate method, called "F1ALA", that utilizes the F1-score to evaluate the confidence with which a specific ancestral node can be annotated as the clade root of a lineage, given the lineage labels of a set of taxa in a rooted tree. Compared to these methods, F1ALA achieved roughly an order of magnitude faster yet with ∼12% of their memory usage when annotating 2277 PANGO lineages in a phylogeny of 5.26 million taxa. F1ALA allows real-time lineage tracking to be performed on a laptop computer. F1ALA outperformed matUtils (pUShER) with statistical significance, and had comparable accuracy to PastML in tests on empirical and simulated data. F1ALA enables a tree refinement by pruning taxa with inconsistent labels to their closest annotation nodes and re-inserting them back to the pruned tree to improve a SARS-CoV-2 phylogeny with both higher log-likelihood and lower parsimony score. Given the ultrafast speed and high accuracy, we anticipated that F1ALA will also be useful for large phylogenies of other viruses. Codes and benchmark datasets are publicly available at https://github.com/id-bioinfo/F1ALA.