Combining wastewater surveillance and case data in estimating the time-varying effective reproduction number.

Wastewater surveillance has been increasingly acknowledged as a useful tool for monitoring transmission dynamics of infections of public health concern, including the coronavirus disease (COVID-19). While a range of models have been proposed to estimate the time-varying effective reproduction number (Rt) utilizing clinical data, few have harnessed the viral concentration in wastewater samples to do so, leaving uncertainties about the potential precision gains with its use. In this study, we developed a Bayesian hierarchical model which simultaneously reconstructed the latent infection trajectory and estimated Rt. Focusing on the 2022 and early 2023 COVID-19 transmission trends in Singapore, where mass community wastewater surveillance has become routine, we performed estimations using a spectrum of data sources, including reported case counts, hospital admissions, deaths, and wastewater viral loads. We further explored the performance of our wastewater model across various scenarios with different sampling strategies. The results showed consistent estimates derived from models employing diverse data streams, while models incorporating more wastewater samples exhibited greater uncertainty and variation in the inferred Rts. Additionally, our analysis revealed prominent day-of-the-week effect in reported case counts and substantial temporal variations in ascertainment rates. In response to these findings, we advocate for a hybrid approach leveraging both clinical and wastewater surveillance data to account for changes in case-ascertainment rates. Furthermore, our study demonstrates the possibility of reducing sampling frequency or sample size without compromising estimation accuracy for Rt, highlighting the potential for optimizing resource allocation in surveillance efforts while maintaining robust insights into the transmission dynamics of infectious diseases.

Feasibility of wastewater-based detection of emergent pandemics through a global network of airports.

Wastewater-based surveillance has been put into practice during the pandemic. Persistence of SARS-CoV-2 in faeces of infected individuals, and high volume of passengers travelling by air, make it possible to detect virus from aircraft wastewater, lending itself to the potential identification of a novel pathogen prior to clinical diagnosis. In this study, we estimated the likelihood of detecting the virus through aircraft wastewater from the probabilities of air travel, viral shedding, defecation, testing sensitivity, and sampling. We considered various hypothetical scenarios, with diverse sampling proportions of inbound flights, surveillance airports, and sources of outbreaks. Our calculations showed that the probability of detecting SARS-CoV-2 would increase exponentially against time in the early phase of the pandemic, and would be much higher if the 20 major airports in Asia, Europe, and North America cooperated to perform aircraft wastewater surveillance. We also found other contributors to early detection, including high sampling proportion of inbound flight at destination airports, small population size of the epicentre relative to the travel volume, and large volume of outbound travelers to major airports around the globe. We concluded that routine aircraft wastewater monitoring could be a feasible approach for early identification and tracking of an emerging pathogen with high faecal shedding rates, particularly when implemented through a global surveillance network of major airports.

COVID-19 vaccine acceptance and its associated factors in the Western Pacific Region.

Background: COVID-19 vaccines effectively reduced the severity of the pandemic, but the mass rollout was challenged by vaccine hesitancy, which was related to heterogenous factors-such as religiosity, mistrust, and a lack of scientific knowledge-around the globe. Distinguishing these potential influencers and quantifying their impacts would help authorities to tailor strategies that boost vaccine confidence and acceptance. Methods: We conducted a large-scale, data-driven analysis on vaccine acceptance and actual uptake in eight Western Pacific countries before (2021) and after (2022) the mass COVID-19 vaccine rollouts. We compared vaccine acceptance or uptake rates between different subpopulations using Bootstrap methods and further constructed a logistic model to investigate the relationship between vaccine endorsement and diverse socio-demographic or trust-related determinants at these two time points. Findings: Substantial between-country differences in vaccine acceptance and uptake were observed across the Western Pacific, with Mongolia, Vietnam, Laos, Cambodia, and Malaysia being more pro-vaccine than the other three countries (Japan, South Korea, and the Philippines). Actual vaccination rates in 2022 were all higher than predicted from the 2021 responses. Influencers for vaccine endorsement were country-specific, but generally, groups susceptible to vaccine hesitancy included females, the less-educated, and those distrusting vaccines or health care providers. Interpretation: Our findings demonstrate the successful translation of vaccine intent to actual uptake with the deployment of COVID-19 vaccination in the Western Pacific. Increasing vaccine confidence and supressing dissemination of misinformation may play an essential role in reducing vaccine hesitancy and ramping up immunisation. Funding: AIR@InnoHK.

Comparison of percutaneous balloon compression and microvascular decompression in the treatment of trigeminal neuralgia.

Objective: To compare the effect of percutaneous balloon compression (PBC) and microvascular decompression (MVD) in the treatment of trigeminal neuralgia (TN). Methods: Data of 98 patients with TN, admitted to Chenzhou First People's Hospital from May 2020 to May 2022, were retrospectively collected. Patients were divided into two groups based on the surgical method. A total of 53 patients treated with PBC comprised the PBC-group and 45 patients treated with MVD comprised the MVD-group. The immediate pain relief, long-term efficacy, surgical complications, and masticatory muscle strength of the two groups were compared and analyzed. Results: There was no significant difference in the immediate pain relief and long-term e efficacy, between the two groups (P>0.05). Complication rate in the PBC-group was significantly lower than that in the MVD-group (3.77% vs 17.78%, P<0.05). Medical records within 14 days after the operation showed that the incidence of facial numbness and masticatory muscle weakness in the PBC-group were 37.74% and 28.30% respectively, significantly higher than those in MVD-group (4.44% and 2.22%) (P<0.05). These symptoms gradually improved three months after the surgery, and were almost completely resolved after six months. Conclusions: Compared with MVD, PBC has the same effect in the treatment of TN. PBC is a minimally invasive, safe, and effective method with a low complication rate. Although masticatory muscle strength is slightly impacted by PBC, it gradually recovers within six months after the operation.

EpiMix: A novel method to estimate effective reproduction number.

Transmission potential of a pathogen, often quantified by the time-varying reproduction number Rt, provides the current pace of infection for a disease and indicates whether an emerging epidemic is under control. In this study, we proposed a novel method, EpiMix, for Rt estimation, wherein we incorporated the impacts of exogenous factors and random effects under a Bayesian regression framework. Using Integrated Nested Laplace Approximation, EpiMix is able to efficiently generate reliable, deterministic Rt estimates. In the simulations and case studies performed, we further demonstrated the method's robustness in low-incidence scenarios, together with other merits, including its flexibility in selecting variables and tolerance of varying reporting rates. All these make EpiMix a potentially useful tool for real-time Rt estimation provided that the serial interval distribution, time series of case counts and external influencing factors are available.

The impact of earlier reopening to travel in the Western Pacific on SARS-CoV-2 transmission.

Background: The COVID-19 pandemic has led to a fall of over 70% in international travel, resulting in substantial economic damages. The impact is especially pronounced in the Asia-Pacific region, where governments have been slow to relax border restrictions. Methods: A retrospective approach was used to construct notional epidemic trajectories for eight Asia-Pacific countries or regions, from June to November 2021, under hypothetical scenarios of earlier resumption of international travel and selective border reopening. The numbers of local infections and deaths over the prediction window were calculated accordingly. Results: Had quarantine-free entry been permitted for all travellers from all the regions investigated, and travel volumes recovered to the 2019 levels, Australia, New Zealand, and Singapore would have been the three most severely affected regions, with at least doubled number of deaths, while infections would have increased marginally (< 5%) for Japan, Malaysia, and Thailand. Conclusions: Earlier resumption of travel in Asia-Pacific, while maintaining a controlled degree of importation risk, could have been implemented through selective border-reopening strategies and on-arrival testing. Once countries had experienced large, localized COVID-19 outbreaks, earlier relaxation of border containment measures would not have resulted in a great increase in morbidity and mortality.

EpiRegress: A Method to Estimate and Predict the Time-Varying Effective Reproduction Number.

The time-varying reproduction (Rt) provides a real-time estimate of pathogen transmissibility and may be influenced by exogenous factors such as mobility and mitigation measures which are not directly related to epidemiology parameters and observations. Meanwhile, evaluating the impacts of these factors is vital for policy makers to propose and adjust containment strategies. Here, we developed a Bayesian regression framework, EpiRegress, to provide Rt estimates and assess impacts of diverse factors on virus transmission, utilising daily case counts, mobility, and policy data. To demonstrate the method's utility, we used simulations as well as data in four regions from the Western Pacific with periods of low COVID-19 incidence, namely: New South Wales, Australia; New Zealand; Singapore; and Taiwan, China. We found that imported cases had a limited contribution on the overall epidemic dynamics but may degrade the quality of the Rt estimate if not explicitly accounted for. We additionally demonstrated EpiRegress's capability in nowcasting disease transmissibility before contemporaneous cases diagnosis. The approach was proved flexible enough to respond to periods of atypical local transmission during epidemic lulls and to periods of mass community transmission. Furthermore, in epidemics where travel restrictions are present, it is able to distinguish the influence of imported cases.

Estimating transmission dynamics of SARS-CoV-2 at different intraspatial levels in an institutional outbreak.

INTRODUCTION: Large, localised outbreaks of COVID-19 have been repeatedly reported in high-density residential institutions. Understanding the transmission dynamics will inform outbreak response and the design of living environments that are more resilient to future outbreaks. METHODS: We developed an individual-based, multilevel transmission dynamics model using case, serology and symptom data from a 60-day cluster randomised trial of prophylaxes in a densely populated foreign worker dormitory in Singapore. Using Bayesian data augmentation, we estimated the basic reproduction number and the contribution that within-room, between-level and across-block transmission made to it, and the prevalence of infection over the study period across different spatial levels. We then simulated the impact of changing the building layouts in terms of floors and blocks on outbreak size. RESULTS: We found that the basic reproduction number was 2.76 averaged over the different putative prophylaxes, with substantial contributions due to transmission beyond the residents' rooms. By the end of ~60 days of follow up, prevalence was 64.4 % (95 % credible interval 64.2-64.6 %). Future outbreak sizes could feasibly be halved by reducing the density to include additional housing blocks, or taller buildings, while retaining the overall number of men in the complex. DISCUSSION: The methods discussed can potentially be utilised to estimate transmission dynamics at any high-density accommodation site with the availability of case and serology data. The restructuring of infrastructure to reduce the number of residents per room can dramatically slow down epidemics, and therefore should be considered by policymakers as a long-term intervention.

Scoping review of the medicinal effects of Eupolyphaga sinensis Walker and the underlying mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Eupolyphaga sinensis Walker (ES) is an insect widely used in traditional East Asian medicine known to exhibit clinical effects on various pathological conditions. Overall, ES is a useful medicinal insect that can treat various diseases, including cancer and immune diseases. However, further mechanistic studies based on its therapeutic effects in clinical settings are required. AIM OF THE STUDY: We aimed to evaluate the current research landscape and diseases associated with ES to synthesize the clinical value of ES based on the associated diseases and underlying therapeutic mechanisms. MATERIALS AND METHODS: Embase and PubMed databases were searched for experimental studies that evaluated the therapeutic efficacy or underlying mechanisms of ES until May 2021. The evidence for each study was summarized using a narrative synthesis approach. Studies on extracted or dried whole ES and ES-derived compounds were quantitatively analyzed by year and disease type. Meanwhile, the overall research trend was confirmed for studies on ES-containing prescriptions by visualizing the disease type analysis. RESULTS: A total of 151 studies were identified, of which 51 were included in our review. There were 14 studies on extracted or dried whole ES, 15 on ES-derived compounds, and 22 on ES-containing prescriptions. ES was most commonly used for cancer-related diseases, followed by those related to endocrine function and immunity. ES regulates the cell cycle, tumor suppressor genes and proteins, immune-related biomarkers, and antioxidant molecules. CONCLUSIONS: Overall, ES is a beneficial medicinal insect that can treat various diseases, including cancer and immune diseases. However, further mechanistic studies based on its therapeutic effects in clinical settings are required.

Testing strategies to contain COVID-19 in migrant worker dormitories.

INTRODUCTION: COVID-19 transmission within overcrowded migrant worker dormitories is an ongoing global issue. Many countries have implemented extensive control measures to prevent the entire migrant worker population from becoming infected. Here, we explore case count outcomes when utilizing lockdown and testing under different testing measures and transmissibility settings. METHODS: We built a mathematical model which estimates transmission across 10 different blocks with 1000 individuals per block under different parameter combinations and testing conditions over the period of 1 month. We vary parameters including differences in block connectivity, underlying recovered proportions at the time of intervention, case importation rates and testing protocols using either PCR or rapid antigen testing. RESULTS: We estimate that a relatively transmissible environment with fortnightly PCR testing at a relatively low initial recovered proportion of 40%, low connectivity where 10% of contacts occurred outside of the infected individuals' block and a high importation rate of 1 100 000 per day, results in an average of 39 (95%Interval: 9-121) new COVID-19 cases after one month of observation. Similar results were observed for weekly rapid antigen testing at 33 (9-95) cases. INTERPRETATION: Our findings support the need for either fortnightly PCR testing or weekly rapid antigen testing in high population density environments such as migrant worker dormitories. Repeated mass testing is highly effective, preventing localized site outbreaks and reducing the need for site wide lockdowns or other extensive social distancing measures within and outside of dormitories.