Using high-resolution contact networks to evaluate SARS-CoV-2 transmission and control in large-scale multi-day events

The emergence of the highly transmissible SARS-CoV-2 Delta variant has created a need to reassess the risk posed by increasing social contacts as countries resume pre-pandemic activities, particularly in the context of resuming large-scale events over multiple days. To examine how social contacts formed in different activity settings influences interventions required to control outbreaks, we combined high-resolution data on contacts among passengers and crew on cruise ships with network transmission models. We found passengers had a median of 20 (IQR 10-36) unique close contacts per day, and over 60% of their contact episodes were made in dining or sports areas where mask wearing is typically limited. In simulated outbreaks, we found that vaccination coverage and rapid antigen tests had a larger effect than mask mandates alone, indicating the importance of combined interventions against Delta to reduce event risk in the vaccine era.

Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine-breakthrough infections: a multi-center cohort study

ObjectivesHighly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns (VOCs) with mutations in the spike protein are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections. MethodsWe conducted a multi-centre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared the clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals. ResultsOf 218 individuals with B.1.617.2 infection, 84 had received a mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and 4 received a non-mRNA. Despite significantly older age in the vaccine breakthrough group, the odds of severe COVID-19 requiring oxygen supplementation was significantly lower following vaccination (adjusted odds ratio 0.07 95%CI: 0.015-0.335, p=0.001). PCR cycle threshold (Ct) values were similar between both vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients, however, these titers were significantly lower against B.1.617.2 as compared with the wildtype vaccine strain. ConclusionThe mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of COVID-19 pandemic.

Serial intervals observed in SARS-CoV-2 B.1.617.2 variant cases

Rapid growth of the SARS-CoV-2 variant B.1.617.2 has been observed in many countries. The factors driving the recent rapid growth of COVID-19 cases could be attributed to shorten generation intervals or higher transmissibility (effective reproduction number, R), or both. Establishing the reasons for the observed rapid growth is key for outbreak control. In this study, we analysed the serial interval of household transmission pairs infected with SARS-CoV-2 B.1.617.2 variant and compared with those who were infected prior to the occurrence of the major global SARS-CoV-2 variants. After controlling for confounding factors, our findings suggest no significant changes in the serial intervals for SARS-CoV-2 cases infected with the B.1.617.2 variant. This, in turn, lends support for the hypothesis of a higher R in B.1.617.2 cases.

Relative role of border restrictions, case finding and contact tracing in controlling SARS-CoV-2 in the presence of undetected transmission

BackgroundSeveral countries have controlled the spread of COVID-19 through varying combinations of border restrictions, case finding, contact tracing and careful calibration on the resumption of domestic activities. However, evaluating the effectiveness of these measures based on observed cases alone is challenging as it does not reflect the transmission dynamics of missed infections. MethodsCombining data on notified local COVID-19 cases with known and unknown sources of infections (i.e. linked and unlinked cases) in Singapore in 2020 with a transmission model, we reconstructed the incidence of missed infections and estimated the relative effectiveness of different types of outbreak control. We also examined implications for estimation of key real-time metrics -- the reproduction number and ratio of unlinked to linked cases, using observed data only as compared to accounting for missed infections. FindingsPrior to the partial lockdown in Singapore, initiated in April 2020, we estimated 89% (95%CI 75-99%) of the infections caused by notified cases were contact traced, but only 12.5% (95%CI 2-69%) of the infections caused by missed infectors were identified. We estimated that the reproduction number was 1.23 (95%CI 0.98-1.54) after accounting for missed infections but was 0.90 (95%CI 0.79-1.1) based on notified cases alone. At the height of the outbreak, the ratio of missed to notified infections was 34.1 (95%CI 26.0-46.6) but the ratio of unlinked to linked infections was 0.81 (95%CI 0.59-1.36). Our results suggest that when case finding and contact tracing identifies at least 50% and 20% of the infections caused by missed and notified cases respectively, the reproduction number could be reduced by more than 14%, rising to 20% when contact tracing is 80% effective. InterpretationDepending on the relative effectiveness of border restrictions, case finding and contact tracing, unobserved outbreak dynamics can vary greatly. Commonly used metrics to evaluate outbreak control -- typically based on notified data -- could therefore misrepresent the true underlying outbreak. FundingMinistry of Health, Singapore. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed, BioRxiv and MedRxiv for articles published in English up to Mar 20, 2021 using the terms: (2019-nCoV OR "novel coronavirus" OR COVID-19 OR SARS-CoV-2) AND (border OR travel OR restrict* OR import*) AND ("case finding" OR surveillance OR test*) AND (contact trac*) AND (model*). The majority of modelling studies evaluated the effectiveness of various combinations of interventions in the absence of outbreak data. For studies that reconstructed the initial spread of COVID-19 with outbreak data, they further simulated counterfactual scenarios in the presence or absence of these interventions to quantify the impact to the outbreak trajectory. None of the studies disentangled the effects of case finding, contact tracing, introduction of imported cases and the reproduction number, in order to reproduce an observed SARS-CoV-2 outbreak trajectory. Added value of this studyNotified COVID-19 cases with unknown and known sources of infection are identified through case finding and contact tracing respectively. Their respective daily incidence and the growth rate over time may differ. By capitalising on these differences in the outbreak data and the use of a mathematical model, we could identify the key drivers behind the growth and decline of both notified and missed COVID-19 infections in different time periods -- e.g. domestic transmission vs external introductions, relative role of case finding and contact tracing in domestic transmission. Estimating the incidence of missed cases also allows us to evaluate the usefulness of common surveillance metrics that rely on observed cases. Implications of all the available evidenceComprehensive outbreak investigation data integrated with mathematical modelling helps to quantify the strengths and weaknesses of each outbreak control intervention during different stages of the pandemic. This would allow countries to better allocate limited resources to strengthen outbreak control. Furthermore, the data and modelling approach allows us to estimate the extent of missed infections in the absence of population wide seroprevalence surveys. This allows us to compare the growth dynamics of notified and missed infections as reliance on the observed data alone may create the illusion of a controlled outbreak.

Comfort and exertion while using filtering facepiece respirators with exhalation valve and an active venting system among male military personnel

<p><b>INTRODUCTION</b>This study aimed to determine if disposable filtering facepiece respirators (FFRs) that come with an exhalation valve (EV) and a novel active venting system (AVS) provided greater perceived comfort and exertion when compared to standard N95 FFRs without these features among male military personnel performing prolonged essential outdoor duties.</p><p><b>METHODS</b>We used a randomised open-label controlled crossover study design to compare three FFR options: (a) standard FFR; (b) FFR with EV; and (c) FFR with EV+AVS. Male military personnel aged between 18 and 20 years completed a questionnaire at the start of outdoor duty (baseline), after two hours of standardised non-strenuous outdoor duty and after 12 hours of duty divided into two-hour work-rest cycles. Participants rated the degree of discomfort, exertion and symptoms using a five-point Likert scale. The association between outcomes and types of FFR was assessed using a multivariate ordered probit mixed-effects model.</p><p><b>RESULTS</b>For a majority of the symptoms, study participants gave FFR with EV and FFR EV+AVS significantly better scores than standard FFR. Both FFR with EV and FFR with EV+AVS had significantly less discomfort (FFR with EV+AVS: 91.1%; FFR with EV: 57.6%) and exertion (FFR with EV+AVS: 83.5%; FFR with EV: 34.4%) than standard FFR. FFR with EV+AVS also had significantly better scores for exertion (53.4%) and comfort (39.4%) when compared to FFR with EV.</p><p><b>CONCLUSION</b>Usage of FFR with EV+AVS resulted in significantly reduced symptoms, discomfort and exertion when compared to FFR with EV and standard FFR.</p>

Utility of COX1 phylogenetics to differentiate between locally acquired and imported Plasmodium knowlesi infections in Singapore

<p><b>INTRODUCTION</b>Although there have been several phylogenetic studies on Plasmodium knowlesi (P. knowlesi), only cytochrome c oxidase subunit 1 (COX1) gene analysis has shown some geographical differentiation between the isolates of different countries.</p><p><b>METHODS</b>Phylogenetic analysis of locally acquired P. knowlesi infections, based on circumsporozoite, small subunit ribosomal ribonucleic acid (SSU rRNA), merozoite surface protein 1 and COX1 gene targets, was performed. The results were compared with the published sequences of regional isolates from Malaysia and Thailand.</p><p><b>RESULTS</b>Phylogenetic analysis of the circumsporozoite, SSU rRNA and merozoite surface protein 1 gene sequences for regional P. knowlesi isolates showed no obvious differentiation that could be attributed to their geographical origin. However, COX1 gene analysis showed that it was possible to differentiate between Singapore-acquired P. knowlesi infections and P. knowlesi infections from Peninsular Malaysia and Sarawak, Borneo, Malaysia.</p><p><b>CONCLUSION</b>The ability to differentiate between locally acquired P. knowlesi infections and imported P. knowlesi infections has important utility for the monitoring of P. knowlesi malaria control programmes in Singapore.</p>

Outbreak of acute norovirus gastroenteritis in a military facility in Singapore: a public health perspective

<p><b>INTRODUCTION</b>Norovirus gastrointestinal disease (GID) outbreaks occur frequently in closed settings, with high attack rates. On October 16, 2008, a norovirus GID outbreak occurred at a Singapore military camp. This study describes the epidemiological investigations conducted to determine the cause of outbreak and the efficacy of the public health measures implemented.</p><p><b>METHODS</b>Epidemiologic investigations included a case-control study of exposure to different food items and an environmental exposure survey. Stool samplings of patients and food handlers for common pathogens, and microbiologic testing of food and water samples were performed. Inspection of dining facilities and health screening of all food-handlers were also conducted.</p><p><b>RESULTS</b>A total of 156 GID cases were reported on October 15-31, 2008. 24 (15.4%) personnel were positive for norovirus. The predominant symptoms were diarrhoea (76.3%) and abdominal pain (69.2%). There was no clinical correlation between any food item and the affected personnel. Testing of food and water samples, dining facility inspections and health screening of food handlers showed satisfactory results. The environmental exposure survey indicated possible transmission due to environmental contamination by vomitus in common areas. Comprehensive environmental decontamination was performed with hypochlorite solution, and personal hygiene measures were enforced. The outbreak lasted 17 days, with a decline in cases post intervention.</p><p><b>CONCLUSION</b>Timely notification and prompt response can curtail disease transmission. Swift implementation of public health measures, such as emphasis on personal hygiene, isolation of affected cases and comprehensive disinfection of the environment, effectively stopped norovirus transmission and may be adapted for future GID outbreaks.</p>

An outbreak of Salmonella gastrointestinal illness in a military camp

<p><b>INTRODUCTION</b>Non-typhoidal Salmonellae are important causes of bacterial food-borne infection, especially in institutional settings. An outbreak of gastrointestinal infection occurred in a military camp in January 2007, and an epidemiological outbreak investigation was conducted.</p><p><b>MATERIALS AND METHODS</b>A survey was conducted on soldiers in the camp on their clinical symptoms, and recent meals consumed. After determining the affected meal, a subsequent survey was conducted on those who had eaten the meal. A case-control study was then performed to determine the outbreak's likely food source. Laboratory tests were also conducted to determine the bacteriological cause.</p><p><b>RESULTS</b>Of the 94 responders, 55 (58.5%) met our case definition of gastrointestinal illness. The dinner on 9 January was the most likely affected meal, with the onset of symptoms occurring within 6 to 36 hours. The mashed potato was the most likely food source with an attack rate of 80.7% for those who consumed it versus 32.7% for those who did not (P <0.01). From the multivariate analysis, the mashed potato remained the only food item independently and significantly associated with infection, with a relative risk of infection 9.49 times those who did not consume it (95% CI, 2.73-32.97). Salmonella group E was cultured from 4 individuals. Although no specific contamination was identified, the mashed potato was stored for more than 5 hours before the last serving.</p><p><b>CONCLUSION</b>Risk during preparation of large quantities of food should be identified a priori, and measures taken to reduce them, to prevent outbreaks.</p>

Twentieth century influenza pandemics in Singapore

<p><b>INTRODUCTION</b>Singapore was substantially affected by three 20th Century pandemics. This study describes the course of the pandemics, and the preventive measures adopted.</p><p><b>MATERIALS AND METHODS</b>We reviewed and researched a wide range of material including peer-reviewed journal articles, Ministry of Health reports, Straits Settlements reports and newspaper articles. Monthly mortality data were obtained from various official sources in Singapore.</p><p><b>RESULTS</b>The 1918 epidemic in Singapore occurred in 2 waves--June to July, and October to November--resulting in up to 3500 deaths. The 1957 epidemic occurred in May, and resulted in widespread morbidity, with 77,000 outpatient attendances in government clinics alone. The 1968 epidemic occurred in August and lasted a few weeks, with outpatient attendances increasing by more than 65%. The preventive measures instituted by the Singapore government during the pandemics included the closure of schools, promulgation of public health messages, setting up of influenza treatment centres, and screening at ports. Students, businessmen and healthcare workers were all severely affected by the pandemics.</p><p><b>CONCLUSIONS</b>Tropical cities should be prepared in case of a future pandemic. Some of the preventive measures used in previous pandemics may be applicable during the next pandemic.</p>

Travel characteristics and health practices among travellers at the travellers' health and vaccination clinic in Singapore

<p><b>INTRODUCTION</b>Singapore has a fast-growing travel industry, but few studies have been done on travel characteristics and travel health practices. This study describes the profile and healthseeking behaviour of travellers attending a travel health clinic in Singapore.</p><p><b>MATERIALS AND METHODS</b>A cross-sectional survey was conducted on travellers attending the Traveller's Health and Vaccination Centre (THVC) between September and November 2002 using a standardised questionnaire. Information obtained included individual demographic and medical information, travel patterns, vaccination status and travel health practices.</p><p><b>RESULTS</b>Four hundred and ninetyfive (74%) eligible travellers seen at THVC responded to the questionnaire. Their mean age was 36 years; 77% were professionals, managers, executives, and businessmen, students, and white collar workers. Asia was the main travel destination, and most travelled for leisure and resided in hotels or hostels. The median duration of travel was 16 days. Although >90% had previously travelled overseas, only 20% had previously sought pre-travel advice. Malays were significantly underrepresented (P < 0.01); and Caucasians and Eurasians were significantly more likely (P < 0.01) to have previously sought pre-travel advice compared with Chinese, Indians and Malays. Factors associated with seeking pre-travel advice included travel outside of Asia, especially Africa and South America.</p><p><b>CONCLUSION</b>Singaporean travellers travel more often to cities rather than rural areas, compared with non-Asian travellers. Asia is the preferred destination, and travel outside of Asia is perceived as more risky and is associated with seeking pre-travel advice and vaccinations. Travel patterns and behaviours need to be taken into account when developing evidence-based travel medicine in Asia.</p>