A system dynamics modelling and analytical framework for imported dengue outbreak surveillance and risk mapping.

System Dynamics (SD) models have been used to understand complex, multi-faceted dengue transmission dynamics, but a gap persists between research and actionable public health tools for decision-making. Spain is an at-risk country of imported dengue outbreaks, but only qualitative assessments are available to guide public health action and control. We propose a modular SD model combining temperature-dependent vector population, transmission parameters, and epidemiological interactions to simulate outbreaks from imported cases accounting for heterogeneous local climate-related transmission patterns. Under our assumptions, 15 provinces sustain vector populations capable of generating outbreaks from imported cases, with heterogeneous risk profiles regarding seasonality, magnitude and risk window shifting from late Spring to early Autum. Results being relative to given vector-to-human populations allow flexibility when translating outcomes between geographic scales. The model and the framework are meant to serve public health by incorporating transmission dynamics and quantitative-qualitative input to the evidence-based decision-making chain. It is a flexible tool that can easily adapt to changing contexts, parametrizations and epidemiological settings thanks to the modular approach.

Spatiotemporal analysis of imported and local dengue virus and cases in a metropolis in Southwestern China, 2013-2022.

Dengue fever is a viral illness, mainly transmitted by Aedes aegypti and Aedes albopictus. With climate change and urbanisation, more urbanised areas are becoming suitable for the survival and reproduction of dengue vector, consequently are becoming suitable for dengue transmission in China. Chongqing, a metropolis in southwestern China, has recently been hit by imported and local dengue fever, experiencing its first local outbreak in 2019. However, the genetic evolution dynamics of dengue viruses and the spatiotemporal patterns of imported and local dengue cases have not yet been elucidated. Hence, this study implemented phylogenetic analyses using genomic data of dengue viruses in 2019 and 2023 and a spatiotemporal analysis of dengue cases collected from 2013 to 2022. We sequenced a total of 15 nucleotide sequences of E genes. The dengue viruses formed separate clusters and were genetically related to those from Guangdong Province, China, and countries in Southeast Asia, including Laos, Thailand, Myanmar and Cambodia. Chongqing experienced a dengue outbreak in 2019 when 168 imported and 1,243 local cases were reported, mainly in September and October. Few cases were reported in 2013-2018, and only six were imported from 2020 to 2022 due to the COVID-19 lockdowns. Our findings suggest that dengue prevention in Chongqing should focus on domestic and overseas population mobility, especially in the Yubei and Wanzhou districts, where airports and railway stations are located, and the period between August and October when dengue outbreaks occur in endemic regions. Moreover, continuous vector monitoring should be implemented, especially during August-October, which would be useful for controlling the Aedes mosquitoes. This study is significant for defining Chongqing's appropriate dengue prevention and control strategies.

Modelling the spatial risk of malaria through probability distribution of Anopheles maculipennis s.l. and imported cases.

Malaria remains one of the most important infectious diseases globally due to its high incidence and mortality rates. The influx of infected cases from endemic to non-endemic malaria regions like Europe has resulted in a public health concern over sporadic local outbreaks. This is facilitated by the continued presence of competent Anopheles vectors in non-endemic countries.We modelled the potential distribution of the main malaria vector across Spain using the ensemble of eight modelling techniques based on environmental parameters and the Anopheles maculipennis s.l. presence/absence data collected from 2000 to 2020. We then combined this map with the number of imported malaria cases in each municipality to detect the geographic hot spots with a higher risk of local malaria transmission.The malaria vector occurred preferentially in irrigated lands characterized by warm climate conditions and moderate annual precipitation. Some areas surrounding irrigated lands in northern Spain (e.g. Zaragoza, Logroño), mainland areas (e.g. Madrid, Toledo) and in the South (e.g. Huelva), presented a significant likelihood of A. maculipennis s.l. occurrence, with a large overlap with the presence of imported cases of malaria.While the risk of malaria re-emergence in Spain is low, it is not evenly distributed throughout the country. The four recorded local cases of mosquito-borne transmission occurred in areas with a high overlap of imported cases and mosquito presence. Integrating mosquito distribution with human incidence cases provides an effective tool for the quantification of large-scale geographic variation in transmission risk and pinpointing priority areas for targeted surveillance and prevention.

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission.

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16-20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement.

Quantifying COVID-19 importation risk in a dynamic network of domestic cities and international countries.

Since its outbreak in December 2019, the novel coronavirus 2019 (COVID-19) has spread to 191 countries and caused millions of deaths. Many countries have experienced multiple epidemic waves and faced containment pressures from both domestic and international transmission. In this study, we conduct a multiscale geographic analysis of the spread of COVID-19 in a policy-influenced dynamic network to quantify COVID-19 importation risk under different policy scenarios using evidence from China. Our spatial dynamic panel data (SDPD) model explicitly distinguishes the effects of travel flows from the effects of transmissibility within cities, across cities, and across national borders. We find that within-city transmission was the dominant transmission mechanism in China at the beginning of the outbreak and that all domestic transmission mechanisms were muted or significantly weakened before importation posed a threat. We identify effective containment policies by matching the change points of domestic and importation transmissibility parameters to the timing of various interventions. Our simulations suggest that importation risk is limited when domestic transmission is under control, but that cumulative cases would have been almost 13 times higher if domestic transmissibility had resurged to its precontainment level after importation and 32 times higher if domestic transmissibility had remained at its precontainment level since the outbreak. Our findings provide practical insights into infectious disease containment and call for collaborative and coordinated global suppression efforts.

Sustainable border control policy in the COVID-19 pandemic: A math modeling study.

BACKGROUND: Imported COVID-19 cases, if unchecked, can jeopardize the effort of domestic containment. We aim to find out what sustainable border control options for different entities (e.g., countries, states) exist during the reopening phases, given their own choice of domestic control measures. METHODS: We propose a SUIHR model, which has built-in imported risk and (1-tier) contact tracing to study the cross-border spreading and control of COVID-19. Under plausible parameter assumptions, we examine the effectiveness of border control policies, in combination with internal measures, to confine the virus and avoid reverting back to more restrictive life styles again. RESULTS: When the basic reproduction number R0 of COVID-19 exceeds 2.5, even 100% effective contact tracing alone is not enough to contain the spreading. For an entity that has completely eliminated the virus domestically, and resumes "normal", without mandatory institutional quarantine, even very strict border control measures combined with effective contact tracing can only delay another outbreak by 6 months. For entities employing a confining domestic control policy, non-increasing net imported cases is sufficient to remain open. CONCLUSIONS: Extremely strict border control in entities, where domestic spreading is currently eliminated (e.g., China), is justifiable. However such harsh measure are not necessary for other places. Entities successfully confining the virus by internal measures can open up to similar entities without additional border controls so long as the imported risk stays non-increasing. Opening the borders to entities lacking sufficient internal control of the virus should be exercised in combination with pre-departure screening and tests upon arrival.

Outbreak of Health Care-associated Novel Coronavirus (SARS-coV-2) COVID-19 infections in the Spring of 2020.

As the Director General of Keio University Hospital, I hereby document the recent outbreak of health care-associated novel coronavirus (SARS-CoV-2) COVID-19 infections at our hospital in the spring of 2020.

Estimating the effect of selective border relaxation on COVID-19 in New Zealand.

AIMS: We developed a model, updated daily, to estimate undetected COVID-19 infections exiting quarantine following selectively opening New Zealand's borders to travellers from low-risk countries. METHODS: The prevalence of infectious COVID-19 cases by country was multiplied by expected monthly passenger volumes to predict the rate of arrivals. The rate of undetected infections entering the border following screening and quarantine was estimated. Level 1, Level 2 and Level 3 countries were defined as those with an active COVID-19 prevalence of up to 1/105, 10/105 and 100/105, respectively. RESULTS: With 65,272 travellers per month, the number of undetected COVID-19 infections exiting quarantine is 1 every 45, 15 and 31 months for Level 1, Level 2 and Level 3 countries, respectively. The overall rate of undetected active COVID-19 infections exiting quarantine is expected to increase from the current 0.40 to 0.50 per month, or an increase of one extra infection every 10 months. CONCLUSIONS: Loosening border restrictions results in a small increase in the rate of undetected COVID-19 infections exiting quarantine, which increases from the current baseline by one infection every 10 months. This information may be useful in guiding decision-making on selectively opening of borders in the COVID-19 era.

Effectiveness of Containment Measures Against COVID-19 in Singapore: Implications for Other National Containment Efforts.

BACKGROUND: We hypothesize that comprehensive surveillance of COVID-19 in Singapore has facilitated early case detection and prompt contact tracing and, with community-based measures, contained spread. We assessed the effectiveness of containment measures by estimating transmissibility (effective reproduction number, (Equation is included in full-text article.)) over the course of the outbreak. METHODS: We used a Bayesian data augmentation framework to allocate infectors to infectees with no known infectors and determine serial interval distribution parameters via Markov chain Monte Carlo sampling. We fitted a smoothing spline to the number of secondary cases generated by each infector by respective onset dates to estimate (Equation is included in full-text article.)and evaluated increase in mean number of secondary cases per individual for each day's delay in starting isolation or quarantine. RESULTS: As of April 1, 2020, 1000 COVID-19 cases were reported in Singapore. We estimated a mean serial interval of 4.6 days [95% credible interval (CI) = 4.2, 5.1] with a SD of 3.5 days (95% CI = 3.1, 4.0). The posterior mean (Equation is included in full-text article.)was below one for most of the time, peaking at 1.1 (95% CI = 1.0, 1.3) on week 9 of 2020 due to a spreading event in one of the clusters. Eight hundred twenty-seven (82.7%) of cases infected less than one person on average. Over an interval of 7 days, the incremental mean number of cases generated per individual for each day's delay in starting isolation or quarantine was 0.03 cases (95% CI = 0.02, 0.05). CONCLUSIONS: We estimate that robust surveillance, active case detection, prompt contact tracing, and quarantine of close contacts kept (Equation is included in full-text article.)below one.

Limited Secondary Transmission of the Novel Coronavirus (SARS-CoV-2) by Asymptomatic and Mild COVID-19 Patients in Bhutan.

As the COVID-19 pandemic continues, there is growing concordance and persisting conflicts on the virus and the disease process. We discuss limited transmissibility of the virus by asymptomatic and mild cases of COVID-19 patients in Bhutan. We followed up the secondary transmission of SARS-CoV-2 in the contacts of asymptomatic and mild COVID-19 patients in Bhutan. Bhutan had 33 confirmed COVID-19 cases in the country as of May 29, 2020. Of these, 22 (67%) were females. Except the first two cases (American tourists), the rest were Bhutanese living outside the country. The mean age of the Bhutanese patients was 26.3 (range 16-33) years. Close contacts of 27 of the 33 cases were followed up for signs and symptoms and COVID-19 positivity. The first two cases had 73 and 97 primary contacts, respectively, and equal number of secondary contacts (224). From the third case, a mandatory 21-day facility quarantine was instituted, all primary contacts were facility quarantined, and there were no secondary contacts. In total, the 27 cases had 1,095 primary contacts and 448 secondary contacts. Of these, 75 individuals were categorized as definite high-risk contacts. Secondary transmission occurred in seven high-risk contacts. Therefore, the overall secondary transmission was 9.0% (7/75) and 0.6% (7/1,095) among the high-risk and primary contacts, respectively. No transmission occurred in the secondary contacts. In contrast to several reports indicating high transmissibility of SARS-CoV-2 in contacts of confirmed cases, the mostly young, asymptomatic, and mild cases of COVID-19 in Bhutan showed limited secondary transmission.

Molecular epidemiological surveillance of Africa and Asia imported malaria in Wuhan, Central China: comparison of diagnostic tools during 2011-2018.

BACKGROUND: Malaria remains a serious public health problem globally. As the elimination of indigenous malaria continues in China, imported malaria has gradually become a major health hazard. Well-timed and accurate diagnoses could support the timely implementation of therapeutic schedules, reveal the prevalence of imported malaria and avoid transmission of the disease. METHODS: Blood samples were collected in Wuhan, China, from August 2011 to December 2018. All patients accepted microscopy and rapid diagnosis test (RDT) examinations. Subsequently, each of the positive or suspected positive cases was tested for four human-infectious Plasmodium species by using 18S rRNA-based nested PCR and Taqman probe-based real-time PCR. The results of the microscopy and the two molecular diagnostic methods were analysed. Importation origins were traced by country, and the prevalence of Plasmodium species was analysed by year. RESULTS: A total of 296 blood samples, including 288 that were microscopy and RDT positive, 7 RDT and Plasmodium falciparum positive, and 1 suspected case, were collected and reanalysed. After application of the two molecular methods and sequencing, 291 cases including 245 P. falciparum, 15 Plasmodium vivax, 20 Plasmodium ovale, 6 Plasmodium malariae and 5 mixed infections (3 P. falciparum + P. ovale, 2 P. vivax + P. ovale) were confirmed. These patients had returned from Africa (95.53%) and Asia (4.47%). Although the prevalence displayed a small-scale fluctuation, the overall trend of the imported cases increased yearly. CONCLUSIONS: These results emphasize the necessity of combined utilization of the four tools for malaria diagnosis in clinic and in field surveys of potential risk regions worldwide including Wuhan.

Use of a rapid electronic survey methodology to estimate blood donors' potential exposure to emerging infectious diseases: Application of a statistically representative sampling methodology to assess risk in US blood centers.

Risk assessments of transfusion-transmitted emerging infectious diseases (EIDs) are complicated by the fact that blood donors' demographics and behaviors can be different from the general population. Therefore, when assessing potential blood donor exposure to EIDs, the use of general population characteristics, such as U.S. travel statistics, may invoke uncertainties that result in inaccurate estimates of blood donor exposure. This may, in turn, lead to the creation of donor deferral policies that do not match actual risk. STUDY DESIGN AND METHODS: This article reports on the development of a system to rapidly assess EID risks for a nationally representative portion of the U.S. blood donor population. To assess the effectiveness of this system, a test survey was developed and deployed to a statistically representative sample frame of blood donors from five blood collecting organizations. Donors were directed to an online survey to ascertain their recent travel and potential exposure to Middle East respiratory syndrome coronavirus (MERS-CoV). RESULTS: A total of 7128 responses were received from 54 256 invitations. The age-adjusted estimated total number of blood donors potentially exposed to MERS-CoV was approximately 15 640 blood donors compared to a lower U.S. general population-based estimate of 9610 blood donors. CONCLUSION: The structured donor demographic sample-based data provided an assessment of blood donors' potential exposure to an emerging pathogen that was 63% larger than the U.S. population-based estimate. This illustrates the need for tailored blood donor-based EID risk assessments that provide more specific demographic risk intelligence and can inform appropriate regulatory decision making.

Molecular and epidemiological characterization of imported malaria cases in Chile.

BACKGROUND: Chile is one of the South American countries certified as malaria-free since 1945. However, the recent increase of imported malaria cases and the presence of the vector Anopheles pseudopunctipennis in previously endemic areas in Chile require an active malaria surveillance programme. METHODS: Specimens from 268 suspected malaria cases-all imported-collected between 2015 and 2018 at the Public Health Institute of Chile (ISP), were diagnosed by microscopy and positive cases were included for epidemiological analysis. A photo-induced electron transfer fluorogenic primer real-time PCR (PET-PCR) was used to confirm the presence of malaria parasites in available blood samples. Sanger sequencing of drug resistance molecular markers (pfk13, pfcrt and pfmdr1) and microsatellite (MS) analysis were performed in confirmed Plasmodium falciparum samples and results were related to origin of infection. RESULTS: Out of the 268 suspected cases, 65 were Plasmodium spp. positive by microscopy. A total of 63% of the malaria patients were male and 37% were female; 43/65 of the patients acquired infections in South American endemic countries. Species confirmation of available blood samples by PET-PCR revealed that 15 samples were positive for P. falciparum, 27 for Plasmodium vivax and 4 were mixed infections. The P. falciparum samples sequenced contained four mutant pfcrt genotypes (CVMNT, CVMET, CVIET and SVMNT) and three mutant pfmdr1 genotypes (Y184F/S1034C/N1042D/D1246Y, Y184F/N1042D/D1246Y and Y184F). MS analysis confirmed that all P. falciparum samples presented different haplotypes according to the suspected country of origin. Four patients with P. vivax infection returned to the health facilities due to relapses. CONCLUSION: The timely detection of polymorphisms associated with drug resistance will contribute to understanding if current drug policies in the country are appropriate for treatment of imported malaria cases and provide information about the most frequent resistant genotypes entering Chile.

Minimizing disease spread on a quarantined cruise ship: A model of COVID-19 with asymptomatic infections.

On February 5 the Japanese government ordered the passengers and crew on the Diamond Princess to start a two week quarantine after a former passenger tested positive for COVID-19. During the quarantine the virus spread rapidly throughout the ship. By February 20, there were 651 cases. We model this quarantine with a SEIR model including asymptomatic infections with differentiated shipboard roles for crew and passengers. The study includes the derivation of the basic reproduction number and simulation studies showing the effect of quarantine with COVID-19 or influenza on the total infection numbers. We show that quarantine on a ship with COVID-19 will lead to significant disease spread if asymptomatic infections are not identified. However, if the majority of the crew and passengers are immune or vaccinated to COVID-19, then quarantine would slow the spread. We also show that a disease similar to influenza, even with a ship with a fully susceptible crew and passengers, could be contained through quarantine measures.

Large SARS-CoV-2 Outbreak Caused by Asymptomatic Traveler, China.

An asymptomatic person infected with severe acute respiratory syndrome coronavirus 2 returned to Heilongjiang Province, China, after international travel. The traveler's neighbor became infected and generated a cluster of >71 cases, including cases in 2 hospitals. Genome sequences of the virus were distinct from viral genomes previously circulating in China.

Confirmation of the absence of local transmission and geographic assignment of imported falciparum malaria cases to China using microsatellite panel.

BACKGROUND: Current methods to classify local and imported malaria infections depend primarily on patient travel history, which can have limited accuracy. Genotyping has been investigated as a complementary approach to track the spread of malaria and identify the origin of imported infections. METHODS: An extended panel of 26 microsatellites (16 new microsatellites) for Plasmodium falciparum was evaluated in 602 imported infections from 26 sub-Saharan African countries to the Jiangsu Province of People's Republic of China. The potential of the 26 microsatellite markers to assign imported parasites to their geographic origin was assessed using a Bayesian method with Markov Chain Monte Carlo (MCMC) as implemented in the program Smoothed and Continuous Assignments (SCAT) with a modification to incorporate haploid genotype data. RESULTS: The newly designed microsatellites were polymorphic and are not in linkage disequilibrium with the existing microsatellites, supporting previous findings of high rate of recombination in sub-Saharan Africa. Consistent with epidemiology inferred from patients' travel history, no evidence for local transmission was found; nearly all genetically related infections were identified in people who travelled to the same country near the same time. The smoothing assignment method assigned imported cases to their likely geographic origin with an accuracy (Angola: 59%; Nigeria: 51%; Equatorial Guinea: 40%) higher than would be achieved at random, reaching statistical significance for Angola and Equatorial Guinea. CONCLUSIONS: Genotyping using an extended microsatellite panel is valuable for malaria case classification and programme evaluation in an elimination setting. A Bayesian method for assigning geographic origin of mammals based on genetic data was adapted for malaria and showed potential for identification of the origin of imported infections.

Antibody Responses after Classroom Exposure to Teacher with Coronavirus Disease, March 2020.

After returning from Europe to the United States, on March 1, 2020, a symptomatic teacher received positive test results for severe acute respiratory syndrome coronavirus 2. Of the 21 students exposed to the teacher in the classroom, serologic results suggested past infection for 2. Classroom contact may result in virus transmission.