The epidemiological characteristics of dengue in high-risk areas of China, 2013-2016.

INTRODUCTION: Dengue has become a more serious human health concern in China, with increased incidence and expanded outbreak regions. The knowledge of the cross-sectional and longitudinal epidemiological characteristics and the evolutionary dynamics of dengue in high-risk areas of China is limited. METHODS: Records of dengue cases from 2013 to 2016 were obtained from the China Notifiable Disease Surveillance System. Full envelope gene sequences of dengue viruses detected from the high-risk areas of China were collected. Maximum Likelihood tree and haplotype network analyses were conducted to explore the phylogenetic relationship of viruses from high-risk areas of China. RESULTS: A total of 56,520 cases was reported in China from 2013 to 2016. During this time, Yunnan, Guangdong and Fujian provinces were the high-risk areas. Imported cases occurred almost year-round, and were mainly introduced from Southeast Asia. The first indigenous case usually occurred in June to August, and the last one occurred before December in Yunnan and Fujian provinces but in December in Guangdong Province. Seven genotypes of DENV 1-3 were detected in the high-risk areas, with DENV 1-I the main genotype and DENV 2-Cosmopolitan the secondary one. The Maximum Likelihood trees show that almost all the indigenous viruses separated into different clusters. DENV 1-I viruses were found to be clustered in Guangdong Province, but not in Fujian and Yunnan, from 2013 to 2015. The ancestors of the Guangdong viruses in the cluster in 2013 and 2014 were most closely related to strains from Thailand or Singapore, and the Guangdong virus in 2015 was most closely related to the Guangdong virus of 2014. Based on closest phylogenetic relationships, viruses from Myanmar possibly initiated further indigenous cases in Yunnan, those from Indonesia in Fujian, while viruses from Thailand, Malaysia, Singapore and Indonesia were predominant in Guangdong Province. CONCLUSIONS: Dengue is still an imported disease in China, although some genotypes continued to circulate in successive years. Viral phylogenies based on the envelope gene suggested periodic introductions of dengue strains into China, primarily from Southeast Asia, with occasional sustained, multi-year transmission in some regions of China.

The burden of hand, foot, and mouth disease among children under different vaccination scenarios in China: a dynamic modelling study.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common illness in young children. A monovalent vaccine has been developed in China protecting against enterovirus-71, bivalent vaccines preventing HFMD caused by two viruses are under development. OBJECTIVE: To predict and compare the incidence of HFMD under different vaccination scenarios in China. METHODS: We developed a compartmental model to capture enterovirus transmission and the natural history of HFMD in children aged 0-5, and calibrated to reported cases in the same age-group from 2015 to 2018. We compared the following vaccination scenarios: different combinations of monovalent and bivalent vaccine; a program of constant vaccination to that of pulse vaccination prior to seasonal outbreaks. RESULTS: We estimate 1,982,819, 2,258,846, 1,948,522 and 2,398,566 cases from 2015 to 2018. Increased coverage of monovalent vaccine from 0 to 80% is predicted to decrease the cases by 797,262 (49.1%). Use of bivalent vaccine at an 80% coverage level would decrease the cases by 828,560. Use of a 2.0× pulse vaccination for the bivalent vaccine in addition to 80% coverage would reduce cases by over one million. The estimated R0 for HFMD in 2015-2018 was 1.08, 1.10, 1.35 and 1.17. CONCLUSIONS: Our results point to the benefit of bivalent vaccine and using a pulse vaccination in specific months over routine vaccination. Other ways to control HFMD include isolation of patients in the early stage of dissemination, more frequent hand-washing and ventilation, and better treatment options for patients.

Sámi traditional medicine: practices, usage, benefit, accessibility and relation to conventional medicine, a scoping review study.

The Sámi Indigenous populations, who live in the arctic Sápmi area across four countries - Norway, Sweden, Finland and the Kola Peninsula of Russia - have practiced traditional medicine (TM) for millennia. However, today Sámi TM is unknown within the Swedish health care services (HCS). The aim of this study is to describe the nature and scope of research conducted on Sámi TM among the four Sápmi countries. This study covers peer-reviewed research published in the English language up to 8 April 2020. From 15 databases, 240 abstracts were identified, and 19 publications met the inclusion criteria for full review. Seventeen studies were conducted in Norway, one in Finland and one in Sweden, none in Russia. In northern Norway, Sámi TM is actively used by the local communities, and is claimed to be effective, but is not accessible within HCS. Holistic worldviews, including spirituality, prevail in Sámi TM from practitioners' selection criteria to health care practices to illness responsibilities. An integration of Sámi TM into HCS is clearly the desire of local communities. Comparisons were made between Sámi TM and conventional medicine on worldviews, on perspectives towards each other, and on integration. More studies are needed in Sweden, Finland and Russia.

Prognostic value of the extent of lymphadenectomy for esophageal cancer-specific survival among T1 patients.

BACKGROUND: Clinically, there are no clear guidelines on the extent of lymphadenectomy in patients with T1 esophageal cancer. Studying the minimum number of lymph nodes for resection may increase cancer-specific survival. METHODS: Patients who underwent esophagectomy and lymphadenectomy at T1 stage were selected from the Surveillance, Epidemiology and End Results Program (United States, 1998-2014). Maximally selected rank and Cox proportional hazard models were used to examine three variables: the number of lymph nodes examined, the number of negative lymph nodes and the lymph node ratio. RESULTS: Approximately 18% had lymph node metastases, where the median values were 10, 10 and 0 for the number of lymph nodes examined, the number of negative lymph nodes and the lymph node ratio, respectively. All three examined variables were statistically associated with cancer-specific survival probability. Dividing patients into two groups shows a clear difference in cancer-specific survival compared to four or five groups for all three variables: there was a 29% decrease in the risk of death with the number of lymph nodes examined ≥14 vs < 14 (hazard ratio 0.71, 95% confidence interval: 0.57-0.89), a 35% decrease in the risk of death with the number of negative lymph nodes ≥13 vs < 13 (hazard ratio 0.65, 95% confidence interval: 0.52-0.81), and an increase of 1.21 times in the risk of death (hazard ratio 2.21, 95% confidence interval: 1.76-2.77) for the lymph node ratio > 0.05 vs ≤ 0.05. CONCLUSIONS: The extent of lymph node dissection is associated with cancer-specific survival, and the minimum number of lymph nodes that need to be removed is 14. The number of negative lymph nodes and the lymph node ratio also have prognostic value after lymphadenectomy among T1 stage patients.

The evolutionary dynamics of DENV 4 genotype I over a 60-year period.

Dengue virus serotype 4 (DENV 4) has had a relatively low prevalence worldwide for decades; however, likely due to data paucity, no study has investigated the epidemiology and evolutionary dynamics of DENV 4 genotype I (DENV 4-I). This study aims to understand the diversity, epidemiology and dynamics of DENV 4-I. We collected 404 full length DENV4-1 envelope (E) gene sequences from 14 countries using two sources: Yunnan Province in China (15 strains during 2013-2016) and GenBank (489 strains up to 2018-01-11). Conducting phylogenetic and phylogeographical analyses, we estimated the virus spread, population dynamics, and selection pressures using different statistical analysis methods (substitution saturation, likelihood mapping, Bayesian coalescent inference, and maximum likelihood estimation). Our results show that during the last 60 years (1956-2016), DENV 4-I was present in mainland and maritime Southeast Asia, the Indian subcontinent, the southern provinces of China, parts of Brazil and Australia. The recent spread of DENV 4-I likely originated in the Philippines and later spread to Thailand. From Thailand, it spread to adjacent countries and eventually the Indian subcontinent. Apparently diverging around years 1957, 1963, 1976 and 1990, the different Clades (Clade I-V) were defined. The mean overall evolution rate of DENV 4-I was 9.74 (95% HPD: 8.68-10.82) × 10-4 nucleotide substitutions/site/year. The most recent common ancestor for DENV 4-I traces back to 1956. While the demographic history of DENV 4-I fluctuated, peaks appeared around 1982 and 2006. While purifying selection dominated the majority of E-gene evolution of DENV 4-I, positive selection characterized Clade III (Vietnam). DENV 4-I evolved in situ in Southeast Asia and the Indian subcontinent. Thailand and Indian acted as the main and secondary virus distribution hubs globally and regionally. Our phylogenetic analysis highlights the need for strengthened regional cooperation on surveillance and sharing of sample sequences to improve global dengue control and cross-border transmission prevention efforts.

Estimating Past, Present, and Future Trends in the Global Distribution and Abundance of the Arbovirus Vector Aedes aegypti Under Climate Change Scenarios.

Background: Aedes aegypti is the principal vector for several important arbovirus diseases, including dengue, chikungunya, yellow fever, and Zika. While recent empirical research has attempted to identify the current global distribution of the vector, the seasonal, and longer-term dynamics of the mosquito in response to trends in climate, population, and economic development over the twentieth and the twenty-first century remains to be elucidated. Methods: In this study, we use a process-based mathematical model to estimate global vector distribution and abundance. The model is based on the lifecycle of the vector and its dependence on climate, and the model sensitivity to socio-economic development is tested. Model parameters were generally empirically based, and the model was calibrated to global databases and time series of occurrence and abundance records. Climate data on temperature and rainfall were taken from CRU TS3.25 (1901-2015) and five global circulation models (CMIP5; 2006-2099) forced by a high-end (RCP8.5) and a low-end (RCP2.6) emission scenario. Socio-economic data on global GDP and human population density were from ISIMIP (1950-2099). Findings: The change in the potential of global abundance in A. aegypti over the last century up to today is estimated to be an increase of 9.5% globally and a further increase of 20 or 30% by the end of this century under a low compared to a high carbon emission future, respectively. The largest increase has occurred in the last two decades, indicating a tipping point in climate-driven global abundance which will be stabilized at the earliest in the mid-twenty-first century. The realized abundance is estimated to be sensitive to socioeconomic development. Interpretation: Our data indicate that climate change mitigation, i.e., following the Paris Agreement, could considerably help in suppressing risks of increased abundance and emergence of A. aegypti globally in the second half of the twenty-first century.

Climate change may enable Aedes aegypti infestation in major European cities by 2100.

BACKGROUND: Climate change allows Aedes aegypti to infest new areas. Consequently, it enables the arboviruses the mosquito transmits -- e.g., dengue, chikungunya, Zika and yellow fever - to emerge in previously uninfected areas. An example is the Portuguese island of Madeira during 2012-13. OBJECTIVE: We aim to understand how climate change will affect the future spread of this potent vector, as an aid in assessing the risk of disease outbreaks and effectively allocating resources for vector control. METHODS: We used an empirically-informed, process-based mathematical model to study the feasibility of Aedes aegypti infestation into continental Europe. Based on established global climate-change scenario data, we assess the potential of Aedes aegypti to establish in Europe over the 21st century by estimating the vector population growth rate for five climate models (GCM5). RESULTS: In a low carbon emission future (RCP2.6), we find minimal change to the current situation throughout the whole of the 21st century. In a high carbon future (RCP8.5), a large parts of southern Europe risks being invaded by Aedes aegypti. CONCLUSION: Our results show that successfully enforcing the Paris Agreement by limiting global warming to below 2 °C significantly lowers the risk for infestation of Aedes aegypti and consequently of potential large-scale arboviral disease outbreaks in Europe within the 21st century.

Prognostic Value of Tumor Length for Cause-Specific Death in Resectable Esophageal Cancer.

BACKGROUND: The current esophageal cancer American Joint Committee on Cancer TNM staging system may not capture the full prognostic implications of the primary tumor. A study is needed to explore the prognostic value of tumor size on esophageal cancer-specific death. METHODS: Patients who underwent surgical resection for non-metastatic esophageal cancer were selected from the Surveillance, Epidemiology and End Results Program database (United States, 1988 to 2014). With the use of statistics methods, maximally selected rank and two hazard models (Cox model and Fine-Gray model), the optimum cutoff point for tumor length in each T classification was estimated and the prognostic value of tumor size on esophageal cancer-specific death was analyzed. RESULTS: A total of 4,447 patients were identified. The median tumor size was significantly correlated with T classification, with the correlation coefficient of 0.43 (p < 0.001). Patients in the T1 to T3 classifications who had larger tumor size showed a larger probability of cancer-specific death. The multivariate Cox model showed that tumor size was significantly associated with an increase in cancer-specific death in T1 (2.15, 95% confidence interval [CI]: 1.72 to 2.69) and T2 (1.31, 95% CI: 1.06 to 1.62) but was marginally significantly associated in T3 (1.12, 95% CI: 1.00 to 1.27) and insignificantly associated in T4 classification (p > 0.1). Similar results were found by using the multivariate Fine-Gray model. CONCLUSIONS: We have found that combining T classification with tumor size can increase the precision in identifying the high-risk groups in T1 to T2 classifications. On the basis of esophageal cancer-specific death our study explores the prognostic cutoff point of tumor size by T classification.

Estimating the probability of dengue virus introduction and secondary autochthonous cases in Europe.

Given the speed of air travel, diseases even with a short viremia such as dengue can be easily exported to dengue naïve areas within 24 hours. We set out to estimate the risk of dengue virus introductions via travelers into Europe and number of secondary autochthonous cases as a result of the introduction. We applied mathematical modeling to estimate the number of dengue-viremic air passengers from 16 dengue-endemic countries to 27 European countries, taking into account the incidence of dengue in the exporting countries, travel volume and the probability of being viremic at the time of travel. Our models estimate a range from zero to 167 air passengers who are dengue-viremic at the time of travel from dengue endemic countries to each of the 27 receiving countries in one year. Germany receives the highest number of imported dengue-viremic air passengers followed by France and the United Kingdom. Our findings estimate 10 autochthonous secondary asymptomatic and symptomatic dengue infections, caused by the expected 124 infected travelers who arrived in Italy in 2012. The risk of onward transmission in Europe is reassuringly low, except where Aedes aegypti is present.

Climate Change and Aedes Vectors: 21st Century Projections for Dengue Transmission in Europe.

Warming temperatures may increase the geographic spread of vector-borne diseases into temperate areas. Although a tropical mosquito-borne viral disease, a dengue outbreak occurred in Madeira, Portugal, in 2012; the first in Europe since 1920s. This outbreak emphasizes the potential for dengue re-emergence in Europe given changing climates. We present estimates of dengue epidemic potential using vectorial capacity (VC) based on historic and projected temperature (1901-2099). VC indicates the vectors' ability to spread disease among humans. We calculated temperature-dependent VC for Europe, highlighting 10 European cities and three non-European reference cities. Compared with the tropics, Europe shows pronounced seasonality and geographical heterogeneity. Although low, VC during summer is currently sufficient for dengue outbreaks in Southern Europe to commence-if sufficient vector populations (either Ae. aegypti and Ae. albopictus) were active and virus were introduced. Under various climate change scenarios, the seasonal peak and time window for dengue epidemic potential increases during the 21st century. Our study maps dengue epidemic potential in Europe and identifies seasonal time windows when major cities are most conducive for dengue transmission from 1901 to 2099. Our findings illustrate, that besides vector control, mitigating greenhouse gas emissions crucially reduces the future epidemic potential of dengue in Europe.

Assessing Seasonal Risks for the Introduction and Mosquito-borne Spread of Zika Virus in Europe.

The explosive Zika virus epidemic in the Americas is amplifying spread of this emerging pathogen into previously unaffected regions of the world, including Europe (Gulland, 2016), where local populations are immunologically naïve. As summertime approaches in the northern hemisphere, Aedes mosquitoes in Europe may find suitable climatic conditions to acquire and subsequently transmit Zika virus from viremic travellers to local populations. While Aedes albopictus has proven to be a vector for the transmission of dengue and chikungunya viruses in Europe (Delisle et al., 2015; ECDC, n.d.) there is growing experimental and ecological evidence to suggest that it may also be competent for Zika virus(Chouin-Carneiro et al., 2016; Grard et al., 2014; Li et al., 2012; Wong et al., 2013). Here we analyze and overlay the monthly flows of airline travellers arriving into European cities from Zika affected areas across the Americas, the predicted monthly estimates of the basic reproduction number of Zika virus in areas where Aedes mosquito populations reside in Europe (Aedes aegypti in Madeira, Portugal and Ae. albopictus in continental Europe), and human populations living within areas where mosquito-borne transmission of Zika virus may be possible. We highlight specific geographic areas and timing of risk for Zika virus introduction and possible spread within Europe to inform the efficient use of human disease surveillance, vector surveillance and control, and public education resources.

Vectorial capacity of Aedes aegypti: effects of temperature and implications for global dengue epidemic potential.

Dengue is a mosquito-borne viral disease that occurs mainly in the tropics and subtropics but has a high potential to spread to new areas. Dengue infections are climate sensitive, so it is important to better understand how changing climate factors affect the potential for geographic spread and future dengue epidemics. Vectorial capacity (VC) describes a vector's propensity to transmit dengue taking into account human, virus, and vector interactions. VC is highly temperature dependent, but most dengue models only take mean temperature values into account. Recent evidence shows that diurnal temperature range (DTR) plays an important role in influencing the behavior of the primary dengue vector Aedes aegypti. In this study, we used relative VC to estimate dengue epidemic potential (DEP) based on the temperature and DTR dependence of the parameters of A. aegypti. We found a strong temperature dependence of DEP; it peaked at a mean temperature of 29.3°C when DTR was 0°C and at 20°C when DTR was 20°C. Increasing average temperatures up to 29°C led to an increased DEP, but temperatures above 29°C reduced DEP. In tropical areas where the mean temperatures are close to 29°C, a small DTR increased DEP while a large DTR reduced it. In cold to temperate or extremely hot climates where the mean temperatures are far from 29°C, increasing DTR was associated with increasing DEP. Incorporating these findings using historical and predicted temperature and DTR over a two hundred year period (1901-2099), we found an increasing trend of global DEP in temperate regions. Small increases in DEP were observed over the last 100 years and large increases are expected by the end of this century in temperate Northern Hemisphere regions using climate change projections. These findings illustrate the importance of including DTR when mapping DEP based on VC.