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.

Use of US Public Health Travel Restrictions during COVID-19 Outbreak on Diamond Princess Ship, Japan, February-April 2020.

Public health travel restrictions (PHTR) are crucial measures during communicable disease outbreaks to prevent transmission during commercial airline travel and mitigate cross-border importation and spread. We evaluated PHTR implementation for US citizens on the Diamond Princess during its coronavirus disease (COVID-19) outbreak in Japan in February 2020 to explore how PHTR reduced importation of COVID-19 to the United States during the early phase of disease containment. Using PHTR required substantial collaboration among the US Centers for Disease Control and Prevention, other US government agencies, the cruise line, and public health authorities in Japan. Original US PHTR removal criteria were modified to reflect international testing protocols and enable removal of PHTR for persons who recovered from illness. The impact of PHTR on epidemic trajectory depends on the risk for transmission during travel and geographic spread of disease. Lessons learned from the Diamond Princess outbreak provide critical information for future PHTR use.

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.

Longitudinal study based on a safety registry for malaria patients treated with artenimol-piperaquine in six European countries.

BACKGROUND: European travellers to endemic countries are at risk of malaria and may be affected by a different range of co-morbidities than natives of endemic regions. The safety profile, especially cardiac issues, of artenimol (previously dihydroartemisinin)-piperaquine (APQ) Eurartesim® during treatment of uncomplicated imported falciparum malaria is not adequately described due to the lack of longitudinal studies in this population. The present study was conducted to partially fill this gap. METHODS: Participants were recruited through Health Care Provider's safety registry in 15 centres across 6 European countries in the period 2013-2016. Adverse events (AE) were collected, with a special focus on cardiovascular safety by including electrocardiogram QT intervals evaluated after correction with either Bazett's (QTcB) or Fridericia's (QTcF) methods, at baseline and after treatment. QTcB and/or QTcF prolongation were defined by a value > 450 ms for males and children and > 470 ms for females. RESULTS: Among 294 participants, 30.3% were women, 13.7% of Caucasian origin, 13.5% were current smoker, 13.6% current alcohol consumer and 42.2% declared at least one illness history. The mean (SD) age and body mass index were 39.8 years old (13.2) and 25.9 kg/m2 (4.7). Among them, 75 reported a total of 129 AE (27 serious), 46 being suspected to be related to APQ (11 serious) and mostly labelled as due to haematological, gastrointestinal, or infection. Women and Non-African participants had significantly (p < 0.05) more AEs. Among AEs, 21 were due to cardiotoxicity (7.1%), mostly QT prolongation, while 6 were due to neurotoxicity (2.0%), mostly dizziness. Using QTcF correction, QT prolongation was observed in 17/143 participants (11.9%), only 2 of them reporting QTcF > 500 ms (milliseconds) but no clinical symptoms. Using QTcB correction increases of > 60 ms were present in 9 participants (6.3%). A trend towards increased prolongation was observed in those over 65 years of age but only a few subjects were in this group. No new safety signal was reported. The overall efficacy rate was 255/257 (99.2%). CONCLUSIONS: APQ appears as an effective and well-tolerated drug for treatment of malaria in patients recruited in European countries. AEs and QT prolongation were in the range of those obtained in larger cohorts from endemic countries. Trial registration This study has been registered in EU Post-Authorization Studies Register as EUPAS6942.

International travel-related control measures to contain the COVID-19 pandemic: a rapid review.

BACKGROUND: In late 2019, the first cases of coronavirus disease 2019 (COVID-19) were reported in Wuhan, China, followed by a worldwide spread. Numerous countries have implemented control measures related to international travel, including border closures, travel restrictions, screening at borders, and quarantine of travellers. OBJECTIVES: To assess the effectiveness of international travel-related control measures during the COVID-19 pandemic on infectious disease transmission and screening-related outcomes. SEARCH METHODS: We searched MEDLINE, Embase and COVID-19-specific databases, including the Cochrane COVID-19 Study Register and the WHO Global Database on COVID-19 Research to 13 November 2020. SELECTION CRITERIA: We considered experimental, quasi-experimental, observational and modelling studies assessing the effects of travel-related control measures affecting human travel across international borders during the COVID-19 pandemic. In the original review, we also considered evidence on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). In this version we decided to focus on COVID-19 evidence only. Primary outcome categories were (i) cases avoided, (ii) cases detected, and (iii) a shift in epidemic development. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts and subsequently full texts. For studies included in the analysis, one review author extracted data and appraised the study. At least one additional review author checked for correctness of data. To assess the risk of bias and quality of included studies, we used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool for observational studies concerned with screening, and a bespoke tool for modelling studies. We synthesised findings narratively. One review author assessed the certainty of evidence with GRADE, and several review authors discussed these GRADE judgements. MAIN RESULTS: Overall, we included 62 unique studies in the analysis; 49 were modelling studies and 13 were observational studies. Studies covered a variety of settings and levels of community transmission. Most studies compared travel-related control measures against a counterfactual scenario in which the measure was not implemented. However, some modelling studies described additional comparator scenarios, such as different levels of stringency of the measures (including relaxation of restrictions), or a combination of measures. Concerns with the quality of modelling studies related to potentially inappropriate assumptions about the structure and input parameters, and an inadequate assessment of model uncertainty. Concerns with risk of bias in observational studies related to the selection of travellers and the reference test, and unclear reporting of certain methodological aspects. Below we outline the results for each intervention category by illustrating the findings from selected outcomes. Travel restrictions reducing or stopping cross-border travel (31 modelling studies) The studies assessed cases avoided and shift in epidemic development. We found very low-certainty evidence for a reduction in COVID-19 cases in the community (13 studies) and cases exported or imported (9 studies). Most studies reported positive effects, with effect sizes varying widely; only a few studies showed no effect. There was very low-certainty evidence that cross-border travel controls can slow the spread of COVID-19. Most studies predicted positive effects, however, results from individual studies varied from a delay of less than one day to a delay of 85 days; very few studies predicted no effect of the measure. Screening at borders (13 modelling studies; 13 observational studies) Screening measures covered symptom/exposure-based screening or test-based screening (commonly specifying polymerase chain reaction (PCR) testing), or both, before departure or upon or within a few days of arrival. Studies assessed cases avoided, shift in epidemic development and cases detected. Studies generally predicted or observed some benefit from screening at borders, however these varied widely. For symptom/exposure-based screening, one modelling study reported that global implementation of screening measures would reduce the number of cases exported per day from another country by 82% (95% confidence interval (CI) 72% to 95%) (moderate-certainty evidence). Four modelling studies predicted delays in epidemic development, although there was wide variation in the results between the studies (very low-certainty evidence). Four modelling studies predicted that the proportion of cases detected would range from 1% to 53% (very low-certainty evidence). Nine observational studies observed the detected proportion to range from 0% to 100% (very low-certainty evidence), although all but one study observed this proportion to be less than 54%. For test-based screening, one modelling study provided very low-certainty evidence for the number of cases avoided. It reported that testing travellers reduced imported or exported cases as well as secondary cases. Five observational studies observed that the proportion of cases detected varied from 58% to 90% (very low-certainty evidence). Quarantine (12 modelling studies) The studies assessed cases avoided, shift in epidemic development and cases detected. All studies suggested some benefit of quarantine, however the magnitude of the effect ranged from small to large across the different outcomes (very low- to low-certainty evidence). Three modelling studies predicted that the reduction in the number of cases in the community ranged from 450 to over 64,000 fewer cases (very low-certainty evidence). The variation in effect was possibly related to the duration of quarantine and compliance. Quarantine and screening at borders (7 modelling studies; 4 observational studies) The studies assessed shift in epidemic development and cases detected. Most studies predicted positive effects for the combined measures with varying magnitudes (very low- to low-certainty evidence). Four observational studies observed that the proportion of cases detected for quarantine and screening at borders ranged from 68% to 92% (low-certainty evidence). The variation may depend on how the measures were combined, including the length of the quarantine period and days when the test was conducted in quarantine. AUTHORS' CONCLUSIONS: With much of the evidence derived from modelling studies, notably for travel restrictions reducing or stopping cross-border travel and quarantine of travellers, there is a lack of 'real-world' evidence. The certainty of the evidence for most travel-related control measures and outcomes is very low and the true effects are likely to be substantially different from those reported here. Broadly, travel restrictions may limit the spread of disease across national borders. Symptom/exposure-based screening measures at borders on their own are likely not effective; PCR testing at borders as a screening measure likely detects more cases than symptom/exposure-based screening at borders, although if performed only upon arrival this will likely also miss a meaningful proportion of cases. Quarantine, based on a sufficiently long quarantine period and high compliance is likely to largely avoid further transmission from travellers. Combining quarantine with PCR testing at borders will likely improve effectiveness. Many studies suggest that effects depend on factors, such as levels of community transmission, travel volumes and duration, other public health measures in place, and the exact specification and timing of the measure. Future research should be better reported, employ a range of designs beyond modelling and assess potential benefits and harms of the travel-related control measures from a societal perspective.

Managing borders during public health emergencies of international concern: a proposed typology of cross-border health measures.

BACKGROUND: The near universal adoption of cross-border health measures during the COVID-19 pandemic worldwide has prompted significant debate about their effectiveness and compliance with international law. The number of measures used, and the range of measures applied, have far exceeded previous public health emergencies of international concern. However, efforts to advance research, policy and practice to support their effective use has been hindered by a lack of clear and consistent definition. RESULTS: Based on a review of existing datasets for cross-border health measures, such as the Oxford Coronavirus Government Response Tracker and World Health Organization Public Health and Social Measures, along with analysis of secondary and grey literature, we propose six categories to define measures more clearly and consistently - policy goal, type of movement (travel and trade), adopted by public or private sector, level of jurisdiction applied, stage of journey, and degree of restrictiveness. These categories are then brought together into a proposed typology that can support research with generalizable findings and comparative analyses across jurisdictions. Addressing the current gaps in evidence about travel measures, including how different jurisdictions apply such measures with varying effects, in turn, enhances the potential for evidence-informed decision-making based on fuller understanding of policy trade-offs and externalities. Finally, through the adoption of standardized terminology and creation of an agreed evidentiary base recognized across jurisdictions, the typology can support efforts to strengthen coordinated global responses to outbreaks and inform future efforts to revise the WHO International Health Regulations (2005). CONCLUSIONS: The widespread use of cross-border health measures during the COVID-19 pandemic has prompted significant reflection on available evidence, previous practice and existing legal frameworks. The typology put forth in this paper aims to provide a starting point for strengthening research, policy and practice.

Study on the COVID-19 infection status, prevention and control strategies among people entering Shenzhen.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) confirmed cases overseas have continued to rise in the last months, and many people overseas have chosen to return to China. This increases the risk of a large number of imported cases which may cause a relapse of the COVID-19 outbreak. In order to prevent imported infection, the Shenzhen government has implemented a closed-loop management strategy using nucleic acid testing (NAT) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and requiring 14 days of medical observation for individuals with an overseas tour history (Hong Kong, Macao, Taiwan province and other countries). Our study aims to describe the status of COVID-19 infection among people entering Shenzhen, and to evaluate the effect of the closed-loop management strategy. METHODS: We undertook a descriptive study and risk analysis by the entry time, time of reporting, and local confirmed cases in countries of origin. The NAT were completed in Shenzhen Center for Disease Control and Prevention (CDC), ten district-level CDCs, and fever clinics. RESULTS: A total of 86,844 people from overseas entered Shenzhen from January 1 to April 18, 2020; there were 39 imported COVID cases and 293 close contacts. The infection rate of people entering was 4.49‰ [95% Confidence interval (CI): 3.26‰-6.05‰]. Fourteen imported cases (35.9%) came from the UK, and nine (23.08%) came from the USA. People entering from the USA since March 9 or from the UK since March 13 are the high-risk population. As of July 17, there have been no new confirmed cases in Shenzhen for 153 days, and the numbers of confirmed case, close contacts, and asymptomatic cases are 0. CONCLUSIONS: The closed-loop management has been effective in preventing imported infection and controlling domestic relapse. The distribution of entry time and report time for imported cases overseas was similar. This shows that it is important to implement closed-loop management at the port of entry.

Control of COVID-19 in Australia through quarantine: the role of special health accommodation (SHA) in New South Wales, Australia.

BACKGROUND: The first COVID-19 cases were diagnosed in Australia on 25 January 2020. Initial epidiemiology showed that the majority of cases were in returned travellers from overseas. One aspect of Public Health response was to introduce compulsory 14 day quarantine for all travellers returning to New South Wales (NSW) by air or sea in Special Health Accommodation (SHA). We aim to outline the establishment of a specialised health quarantine accommodation service in the context of the COVID-19 pandemic, and describe the first month of COVID-19 screening. METHODS: The SHA was established with a comprehensive governance structure, remote clinical management through Royal Prince Alfred Virtual Hospital (rpavirtual) and site management with health care workers, NSW Police and accommodation staff. RESULTS: From 29 March to 29 April 2020, 373 returning travellers were admitted to the SHA from Sydney Airport. 88 (26.1%) of those swabbed were positive for SARS-CoV 2. The day of diagnosis of COVID-19 varied from Day 1 to Day 13, with 63.6% (n = 56) of these in the first week of quarantine. 50% of the people in the SHA were referred to rpavirtual for ongoing clinical management. Seven people required admission to hospital for ongoing clinical care. CONCLUSION: The Public Health response to COVID-19 in Australia included early and increased case detection through testing, tracing of contacts of confirmed cases, social distancing and prohibition of gatherings. In addition to these measures, the introduction of mandated quarantine for travellers to Australia was integral to the successful containment of COVID-19 in NSW and Australia through the prevention of transmission locally and interstate from returning travellers.

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.

Risk Assessment and Management of COVID-19 Among Travelers Arriving at Designated U.S. Airports, January 17-September 13, 2020.

In January 2020, with support from the U.S. Department of Homeland Security (DHS), CDC instituted an enhanced entry risk assessment and management (screening) program for air passengers arriving from certain countries with widespread, sustained transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). The objectives of the screening program were to reduce the importation of COVID-19 cases into the United States and slow subsequent spread within states. Screening aimed to identify travelers with COVID-19-like illness or who had a known exposure to a person with COVID-19 and separate them from others. Screening also aimed to inform all screened travelers about self-monitoring and other recommendations to prevent disease spread and obtain their contact information to share with public health authorities in destination states. CDC delegated postarrival management of crew members to airline occupational health programs by issuing joint guidance with the Federal Aviation Administration.* During January 17-September 13, 2020, a total of 766,044 travelers were screened, 298 (0.04%) of whom met criteria for public health assessment; 35 (0.005%) were tested for SARS-CoV-2, and nine (0.001%) had a positive test result. CDC shared contact information with states for approximately 68% of screened travelers because of data collection challenges and some states' opting out of receiving data. The low case detection rate of this resource-intensive program highlighted the need for fundamental change in the U.S. border health strategy. Because SARS-CoV-2 infection and transmission can occur in the absence of symptoms and because the symptoms of COVID-19 are nonspecific, symptom-based screening programs are ineffective for case detection. Since the screening program ended on September 14, 2020, efforts to reduce COVID-19 importation have focused on enhancing communications with travelers to promote recommended preventive measures, reinforcing mechanisms to refer overtly ill travelers to CDC, and enhancing public health response capacity at ports of entry. More efficient collection of contact information for international air passengers before arrival and real-time transfer of data to U.S. health departments would facilitate timely postarrival public health management, including contact tracing, when indicated. Incorporating health attestations, predeparture and postarrival testing, and a period of limited movement after higher-risk travel, might reduce risk for transmission during travel and translocation of SARS-CoV-2 between geographic areas and help guide more individualized postarrival recommendations.

Detection of remaining Plasmodium DNA and gametocytes during follow up after curative malaria treatment among returned travellers in Norway.

BACKGROUND: PCR can be positive weeks after effective malaria treatment, potentially leading to over diagnose of recrudescence and re-infections. The DNA detected by PCR post-treatment might stem from residuals of destroyed asexual parasites, or from live gametocytes. The objective of this clinical observational study was to describe the presence of positive PCR for Plasmodium falciparum and Plasmodium vivax in follow-up samples post-treatment from returned travellers, and the proportion of positive PCR due to gametocytes. METHODS: Whole blood was collected during hospitalization and outpatient routine follow-up from 13 patients with imported malaria. DNA was extracted applying QIAamp DNA Blood Mini Kit, while mRNA was collected and extracted applying PAXgene Blood RNA Tubes and Kit. All DNA samples (N = 25) were analysed with a genus-specific cytb real-time SYBR PCR, and P. falciparum DNA samples (N = 22) were also analysed with a falciparum-specific varATS real-time TaqMan PCR. All the mRNA samples (N = 18) were analysed with both a genus-specific 18S rRNA RT-PCR and a gametocyte-specific Pfs25 (P. falciparum)/Pvs25 (P. vivax) RT-PCR. RESULTS: Latest samples were collected at day 1 (n = 2) and from day 11-54 (n = 11) after treatment. Genus DNA cytb PCR was positive up to 49 days after effective treatment, and 18S rRNA transcripts from active P. falciparum parasites were detectable for at least 11 days. Gametocyte-specific mRNA was detected at latest only two days after treatment. Among six patients with late positive PCR for P. falciparum, four had high parasitaemia at admittance (6-30%), while two had parasitaemia < 2%. Late detection of P. vivax was not found by any of the PCR methods. CONCLUSIONS: DNA-based PCR can be positive up to at least seven weeks after curative malaria treatment, potentially leading to over-diagnose of recrudescence and re-infections. Based on the observations in this study, it is unclear if the DNA origins from residuals of destroyed parasites or live gametocytes, warranting further investigations.

Preventing the re-establishment of malaria in Sri Lanka amidst the COVID-19 pandemic.

The COVID-19 pandemic has had a considerable impact on other health programmes in countries, including on malaria, and is currently under much discussion. As many countries are accelerating efforts to eliminate malaria or to prevent the re-establishment of malaria from recently eliminated countries, the COVID-19 pandemic has the potential to cause major interruptions to ongoing anti-malaria operations and risk jeopardizing the gains that have been made so far. Sri Lanka, having eliminated malaria in 2012, was certified by the World Health Organization as a malaria-free country in 2016 and now implements a rigorous programme to prevent its re-establishment owing to the high receptivity and vulnerability of the country to malaria. Sri Lanka has also dealt with the COVID-19 epidemic quite successfully limiting the cumulative number of infections and deaths through co-ordinated efforts between the health sector and other relevant sectors, namely the military, the Police Department, Departments of Airport and Aviation and Foreign Affairs, all of which have been deployed for the COVID-19 epidemic under the umbrella of a Presidential Task Force. The relevance of imported infections and the need for a multi-sectoral response are features common to both the control of the COVID-19 epidemic and the Prevention of Re-establishment (POR) programme for malaria. Sri Lanka's malaria POR programme has, therefore, creatively integrated its activities with those of the COVID-19 control programme. Through highly coordinated operations the return to the country of Sri Lankan nationals stranded overseas by the COVID-19 pandemic, many from malaria endemic countries, are being monitored for malaria as well as COVID-19 in an integrated case surveillance system under quarantine conditions, to the success of both programmes. Twenty-three imported malaria cases were detected from February to October through 2773 microscopic blood examinations performed for malaria in quarantine centres, this number being not much different to the incidence of imported malaria during the same period last year. This experience highlights the importance of integrated case surveillance and the need for a highly coordinated multi-sectoral approach in dealing with emerging new infections. It also suggests that synergies between the COVID-19 epidemic control programme and other health programmes may be found and developed to the advantage of both.

Travel-related control measures to contain the COVID-19 pandemic: a rapid review.

BACKGROUND: In late 2019, first cases of coronavirus disease 2019, or COVID-19, caused by the novel coronavirus SARS-CoV-2, were reported in Wuhan, China. Subsequently COVID-19 spread rapidly around the world. To contain the ensuing pandemic, numerous countries have implemented control measures related to international travel, including border closures, partial travel restrictions, entry or exit screening, and quarantine of travellers. OBJECTIVES: To assess the effectiveness of travel-related control measures during the COVID-19 pandemic on infectious disease and screening-related outcomes. SEARCH METHODS: We searched MEDLINE, Embase and COVID-19-specific databases, including the WHO Global Database on COVID-19 Research, the Cochrane COVID-19 Study Register, and the CDC COVID-19 Research Database on 26 June 2020. We also conducted backward-citation searches with existing reviews. SELECTION CRITERIA: We considered experimental, quasi-experimental, observational and modelling studies assessing the effects of travel-related control measures affecting human travel across national borders during the COVID-19 pandemic. We also included studies concerned with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) as indirect evidence. Primary outcomes were cases avoided, cases detected and a shift in epidemic development due to the measures. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome. DATA COLLECTION AND ANALYSIS: One review author screened titles and abstracts; all excluded abstracts were screened in duplicate. Two review authors independently screened full texts. One review author extracted data, assessed risk of bias and appraised study quality. At least one additional review author checked for correctness of all data reported in the 'Risk of bias' assessment, quality appraisal and data synthesis. For assessing the risk of bias and quality of included studies, we used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool for observational studies concerned with screening, ROBINS-I for observational ecological studies and a bespoke tool for modelling studies. We synthesised findings narratively. One review author assessed certainty of evidence with GRADE, and the review author team discussed ratings. MAIN RESULTS: We included 40 records reporting on 36 unique studies. We found 17 modelling studies, 7 observational screening studies and one observational ecological study on COVID-19, four modelling and six observational studies on SARS, and one modelling study on SARS and MERS, covering a variety of settings and epidemic stages. Most studies compared travel-related control measures against a counterfactual scenario in which the intervention measure was not implemented. However, some modelling studies described additional comparator scenarios, such as different levels of travel restrictions, or a combination of measures. There were concerns with the quality of many modelling studies and the risk of bias of observational studies. Many modelling studies used potentially inappropriate assumptions about the structure and input parameters of models, and failed to adequately assess uncertainty. Concerns with observational screening studies commonly related to the reference test and the flow of the screening process. Studies on COVID-19 Travel restrictions reducing cross-border travel Eleven studies employed models to simulate a reduction in travel volume; one observational ecological study assessed travel restrictions in response to the COVID-19 pandemic. Very low-certainty evidence from modelling studies suggests that when implemented at the beginning of the outbreak, cross-border travel restrictions may lead to a reduction in the number of new cases of between 26% to 90% (4 studies), the number of deaths (1 study), the time to outbreak of between 2 and 26 days (2 studies), the risk of outbreak of between 1% to 37% (2 studies), and the effective reproduction number (1 modelling and 1 observational ecological study). Low-certainty evidence from modelling studies suggests a reduction in the number of imported or exported cases of between 70% to 81% (5 studies), and in the growth acceleration of epidemic progression (1 study). Screening at borders with or without quarantine Evidence from three modelling studies of entry and exit symptom screening without quarantine suggests delays in the time to outbreak of between 1 to 183 days (very low-certainty evidence) and a detection rate of infected travellers of between 10% to 53% (low-certainty evidence). Six observational studies of entry and exit screening were conducted in specific settings such as evacuation flights and cruise ship outbreaks. Screening approaches varied but followed a similar structure, involving symptom screening of all individuals at departure or upon arrival, followed by quarantine, and different procedures for observation and PCR testing over a period of at least 14 days. The proportion of cases detected ranged from 0% to 91% (depending on the screening approach), and the positive predictive value ranged from 0% to 100% (very low-certainty evidence). The outcomes, however, should be interpreted in relation to both the screening approach used and the prevalence of infection among the travellers screened; for example, symptom-based screening alone generally performed worse than a combination of symptom-based and PCR screening with subsequent observation during quarantine. Quarantine of travellers Evidence from one modelling study simulating a 14-day quarantine suggests a reduction in the number of cases seeded by imported cases; larger reductions were seen with increasing levels of quarantine compliance ranging from 277 to 19 cases with rates of compliance modelled between 70% to 100% (very low-certainty evidence). AUTHORS' CONCLUSIONS: With much of the evidence deriving from modelling studies, notably for travel restrictions reducing cross-border travel and quarantine of travellers, there is a lack of 'real-life' evidence for many of these measures. The certainty of the evidence for most travel-related control measures is very low and the true effects may be substantially different from those reported here. Nevertheless, some travel-related control measures during the COVID-19 pandemic may have a positive impact on infectious disease outcomes. Broadly, travel restrictions may limit the spread of disease across national borders. Entry and exit symptom screening measures on their own are not likely to be effective in detecting a meaningful proportion of cases to prevent seeding new cases within the protected region; combined with subsequent quarantine, observation and PCR testing, the effectiveness is likely to improve. There was insufficient evidence to draw firm conclusions about the effectiveness of travel-related quarantine on its own. Some of the included studies suggest that effects are likely to depend on factors such as the stage of the epidemic, the interconnectedness of countries, local measures undertaken to contain community transmission, and the extent of implementation and adherence.

Implications for border containment strategies when COVID-19 presents atypically.

OBJECTIVES: For a large part of the coronavirus disease 2019 (COVID-19) pandemic, Singapore had managed to keep local cases in the single digits daily, with decisive measures. Yet, we saw this critical time point when the imported cases surged through our borders. The gaps which we can and have efficiently closed, using a public health approach and global border containment strategies, are aptly illustrated through this case. This critical point of imported case surge has resulted in a large spike of daily local cases sustained through community transmission, up to 120/day within a very short time frame. We were able to rapidly bring this under control. STUDY DESIGN: This is a case study of a patient who passed through our borders, with COVID-19 masquerading as a resolved sore throat. METHODS: The events were prospectively documented. RESULTS: We present a case of a 21-year-old student returning from Nottingham. He presented with sore throat as the only symptom the few days prior his return, and on arrival at our border (day 7 from initial symptoms), his sore throat had already resolved. The events leading up to his COVID-19 diagnosis highlight the gaps of the international screening processes at the global border entry and the potential consequences of community chain transmission through imported COVID-19 cases. CONCLUSIONS: An important global border control measure to implement quickly will be to expand the symptom list to isolated sore throat and/or a prior history of recent symptoms (resolved). This may capture a larger proportion of imported cases at border entry point for more effective containment. This piece will be equally relevant to the general physicians, emergency care physicians, otolaryngologists and anaesthetists, who are at higher risk of encountering a throat visualization during intubation and routine examination. This information can be useful to countries with low resources or insufficient COVID-19 testing kits.

[Imported infections of the central nervous system : Migration and travel neurology]. / Importierte Infektionen des Zentralnervensystems : Migrations- und Reise-Neurologie.

The numbers of migrants, refugees and asylum seekers reached an unprecedented high in Europe in 2015 and 2016 but in 2019 they are back to the average numbers of the last 30 years. In contrast, frequencies of international and intercontinental travelers have continuously increased over the past decades and will continue to do so in the coming years. In 2018 more than 1.35 billion incoming travelers were reported worldwide by international organizations. Detailed knowledge of the epidemiology, transmission types, risk behavior and clinical presentation of acute and chronic central nervous system (CNS) infections enables timely diagnosis and initiation of potentially life-saving emergency treatment. Acute infections of the CNS, e.g. cerebral Plasmodium falciparum malaria or arboviral encephalitis, are seen most frequently and almost exclusively in travelers returning from tropical countries, whereas chronic CNS infections, e.g. tuberculous meningitis or neurocysticercosis, are typically seen in migrants and refugees. Beside CNS infections genetic diseases, environment-associated, nutrition-related, metabolic or cerebrovascular diseases also need to be considered when discussing differential diagnostic possibilities.

International Importations of Measles Virus into the United States During the Postelimination Era, 2001-2016.

BACKGROUND: Although measles was declared eliminated from the United States in 2000, measles cases and outbreaks continue to occur, resulting from importations of the disease from countries where it remains endemic. METHODS: We describe the epidemiology of international importations of measles virus into the United States during the postelimination era. RESULTS: From 2001 to 2016, 553 imported measles cases were reported to the Centers for Disease Control and Prevention. A median of 28 importations occurred each year (range: 18-80). The median age of imported case-patients was 18 years (range: 3 months-75 years); 87% were unvaccinated or had an unknown vaccination status. US residents (as opposed to foreign visitors) accounted for 62% of imported measles cases. Overall, 62% of all imported case-patients reported travel to countries in the Western Pacific and European Regions of the World Health Organization during their exposure periods. The number of measles importations from specific countries was related to the incidence of measles in and the volume of travel to and from the source country. CONCLUSIONS: Our findings emphasize the importance of measles vaccination of US residents aged ≥6 months before international travel according to the Advisory Committee on Immunization Practices recommendations and supporting global measles elimination efforts.

The Clinical Impact and Cost-effectiveness of Measles-Mumps-Rubella Vaccination to Prevent Measles Importations Among International Travelers From the United States.

BACKGROUND: Measles importations and the subsequent spread from US travelers returning from abroad are responsible for most measles cases in the United States. Increasing measles-mumps-rubella (MMR) vaccination among departing US travelers could reduce the clinical impact and costs of measles in the United States. METHODS: We designed a decision tree to evaluate MMR vaccination at a pretravel health encounter (PHE), compared with no encounter. We derived input parameters from Global TravEpiNet data and literature. We quantified Riskexposure to measles while traveling and the average number of US-acquired cases and contacts due to a measles importation. In sensitivity analyses, we examined the impact of destination-specific Riskexposure, including hot spots with active measles outbreaks; the percentage of previously-unvaccinated travelers; and the percentage of travelers returning to US communities with heterogeneous MMR coverage. RESULTS: The no-encounter strategy projected 22 imported and 66 US-acquired measles cases, costing $14.8M per 10M travelers. The PHE strategy projected 15 imported and 35 US-acquired cases at $190.3M per 10M travelers. PHE was not cost effective for all international travelers (incremental cost-effectiveness ratio [ICER] $4.6M/measles case averted), but offered better value (ICER <$100 000/measles case averted) or was even cost saving for travelers to hot spots, especially if travelers were previously unvaccinated or returning to US communities with heterogeneous MMR coverage. CONCLUSIONS: PHEs that improve MMR vaccination among US international travelers could reduce measles cases, but are costly. The best value is for travelers with a high likelihood of measles exposure, especially if the travelers are previously unvaccinated or will return to US communities with heterogeneous MMR coverage.

Mucosal Leishmaniasis in Travelers with Leishmania braziliensis Complex Returning to Israel.

Mucosal leishmaniasis (ML) is a complication of New World cutaneous leishmaniasis (CL) caused mainly by Leishmania (Viannia) braziliensis. This retrospective study investigated all cases of ML caused by L. (V.) braziliensis in a tertiary medical center in Israel, evaluating the risk factors, clinical presentations, diagnosis, treatment, and outcome of mucosal involvement in ML caused by L. (V.) braziliensis in travelers returning to Israel. During 1993-2015, a total of 145 New World CL cases were seen in travelers returning from Bolivia; among them, 17 (11.7%) developed ML. Nasopharyngeal symptoms developed 0-3 years (median 8 months) after exposure. The only significant risk factor for developing ML was the absence of previous systemic treatment. Among untreated patients, 41% developed ML, compared with only 3% of treated patients (p = 0.005). Systemic treatment for CL seems to be a protective factor against developing ML.

Management of imported malaria cases and healthcare institutions in central China, 2012-2017: application of decision tree analysis.

BACKGROUND: Imported malaria has been an important challenge for China. Fatality rates from malaria increased in China, particularly in Henan Province, primarily due to malpractice and misdiagnoses in healthcare institutions, and the level of imported malaria. This study aims to investigate the relationship between the state of diagnosis and subsequent complications among imported malaria cases at healthcare institutions, based on malaria surveillance data in Henan Province from 2012 to 2017. METHODS: A retrospective descriptive analysis was performed using data from the Centre for Disease Control and Prevention, Zhengzhou City, the capital of Henan Province. A decision tree method was exploited to provide valuable insight into the correlation between imported malaria cases and healthcare institutions. RESULTS: From 2012 to 2017, there were 371 imported malaria cases, mostly in males aged between 20 and 50 years, including 319 Plasmodium falciparum cases. First visits of 32.3%, 19.9% and 15.9% malaria cases for treatment were to provincial, municipal and county healthcare institutions, respectively. The time interval between onset and initial diagnosis of 284 cases (76.5%) and the time interval between initial diagnosis and final diagnosis of 197 cases (53.1%) was no more than 72 h. An apparent trend was found that there were notably fewer patients misdiagnosed at first visit to healthcare institutions of a higher administrative level; 12.5% of cases were misdiagnosed in provincial healthcare institutions compared to 98.2% in private clinics, leading to fewer complications at healthcare institutions of higher administrative level due to correct initial diagnosis. In the tree model, the rank of healthcare facilities for initial diagnosis, and number of days between onset and initial diagnosis, made a major contribution to the classification of initial diagnosis, which subsequently became the most significant factor influencing complications developed in the second tree model. The classification accuracy were 82.2 and 74.1%, respectively for the tree models of initial diagnosis and complications developed. CONCLUSION: Inadequate seeking medical care by imported malaria patients, and insufficient capacity to diagnose malaria by healthcare institutions of lower administrative level were identified as major factors influencing complications of imported malaria cases in Henan Province. The lack of connection between uncommon imported malaria cases and superior medical resources was found to be the crucial challenge. A web-based system combined with WeChat to target imported malaria cases was proposed to cope with the challenge.

A comparison of two PCR protocols for the differentiation of Plasmodium ovale species and implications for clinical management in travellers returning to Germany: a 10-year cross-sectional study.

BACKGROUND: To assess the occurrence of Plasmodium ovale wallikeri and Plasmodium ovale curtisi species in travellers returning to Germany, two real-time PCR protocols for the detection and differentiation of the two P. ovale species were compared. Results of parasite differentiation were correlated with patient data. METHODS: Residual nucleic acid extractions from EDTA blood samples of patients with P. ovale spp. malaria, collected between 2010 and 2019 at the National Reference Centre for Tropical Pathogens in Germany, were subjected to further parasite discrimination in a retrospective assessment. All samples had been analysed by microscopy and by P. ovale spp.-specific real-time PCR without discrimination on species level. Two different real-time PCR protocols for species discrimination of P. o. curtisi and P. o. wallikeri were carried out. Results were correlated with patient data on gender, age, travel destination, thrombocyte count, and duration of parasite latency. RESULTS: Samples from 77 P. ovale spp. malaria patients were assessed, with a male:female ratio of about 2:1 and a median age of 30 years. Parasitaemia was low, ranging from few visible parasites up to 1% infected erythrocytes. Discriminative real-time PCRs revealed 41 cases of P. o. curtisi and 36 cases of P. o. wallikeri infections. Concordance of results by the two PCR approaches was 100%. Assessment of travel destinations confirmed co-existence of P. o. curtisi and P. o. wallikeri over a wide range of countries in sub-Saharan Africa. Latency periods for the two P. ovale species were similar, with median values of 56.0 days for P. o. curtisi and 58.0 days for P. o. wallikeri; likewise, there was no statistically significant difference in thrombocyte count with median values of 138.5/µL for patients with P. o. curtisi and 152.0/µL for P. o. wallikeri-infected patients. CONCLUSIONS: Two different real-time PCR protocols were found to be suitable for the discrimination of P. o. curtisi and P. o. wallikeri with only minor differences in sensitivity. Due to the overall low parasitaemia and the lack of differences in severity-related aspects like parasite latency periods or thrombocyte counts, this study supports the use of P. ovale spp. PCR without discrimination on species level to confirm the diagnosis and to inform clinical management of malaria in these patients.