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  • 1. Lillepold, Kate
    et al.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Liu-Helmersson, Jing
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Sewe, Maquins
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Semenza, Jan C.
    More arboviral disease outbreaks in continental Europe due to the warming climate?2019In: Journal of Travel Medicine, ISSN 1195-1982, E-ISSN 1708-8305Article in journal (Refereed)
  • 2.
    Liu-Helmersson, Jing
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Climate Change, Dengue and Aedes Mosquitoes: Past Trends and Future Scenarios2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background Climate change, global travel and trade have facilitated the spread of Aedes mosquitoes and have consequently enabled the diseases they transmit (dengue fever, Chikungunya, Zika and yellow fever) to emerge and re-emerge in uninfected areas. Large dengue outbreaks occurred in Athens in 1927 and in Portuguese island, Madeira in 2012, but there are almost no recent reports of Aedes aegypti, the principal vector, in Europe. A dengue outbreak needs four conditions: sufficient susceptible humans, abundant Aedes vector, dengue virus introduction, and conducive climate. Can Aedes aegypti establish themselves again in Europe in the near future if they are introduced? How do the current and future climate affect dengue transmission globally, and regionally as in Europe? This thesis tries to answer these questions.

    Methods Two process-based mathematical models were developed in this thesis. Model 1 describes a vector’s ability to transmit dengue – vectorial capacity – based on temperature and diurnal temperature range (DTR). Model 2 describes vector population dynamics based on the lifecycle of Aedes aegypti. From this model, vector abundance was estimated using both climate as a single driver, and climate together with human population and GDP as multiple drivers; vector population growth rate was derived as a threshold condition to estimate the vector’s invasion to a new place.

    Results Using vectorial capacity, we estimate dengue epidemic potential globally for Aedes aegypti and in Europe for Aedes aegypti and Aedes albopictus. We show that mean temperature and DTR are both important in modelling dengue transmission, especially in a temperate climate zone like Europe. Currently, South Europe is over the threshold for dengue epidemics if sufficient dengue vectors are present. Aedes aegypti is on the borderline of invasion into the southern tip of Europe. However, by end of this century, the invasion of Aedes aegypti may reach as far north as the middle of Europe under the business-as-usual climate scenario. Or it may be restricted to the south Europe from the middle of the century if the low carbon emission – Paris Agreement – is implemented to limit global warming to below 2°C.

    Conclusion Climate change will increase the area and time window for Aedes aegypti’s invasion and consequently the dengue epidemic potential globally, and in Europe in particular. Successfully achieving the Paris Agreement would considerably change the future risk scenario of a highly competent vector – Aedes aegypti’s – invasion into Europe. Therefore, the risk of transmission of dengue and other infectious diseases to the mainland of Europe depends largely on human efforts to mitigate climate change.

  • 3.
    Liu-Helmersson, Jing
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Brännström, Åke
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Evolution and Ecology Program, International Institute for Applied Systems Analysis, Laxenburg, Austria.
    Sewe, Maquins
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Estimating past, present and future trends in the global distribution and abundance of the arbovirus vector Aedes aegypti2019In: Frontiers In Public Health, ISSN 2296-2565, Vol. 7, article id 148Article in journal (Other academic)
    Abstract [en]

    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.

  • 4.
    Liu-Helmersson, Jing
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Quam, Mikkel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Stenlund, Hans
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Wilder-Smith, Annelies
    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
    Ebi, K
    Massad, E
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Seasonality of dengue epidemic potential in Europe - based on vectorial capacity for Aedes mosquitoes2015In: Tropical medicine & international health, ISSN 1360-2276, E-ISSN 1365-3156, Vol. 20, no Suppl. 1, p. 113-113Article in journal (Other academic)
    Abstract [en]

    Introduction: Dengue is a mosquito-borne viral infection that has become a major public health concern. About 390 million people are infected yearly. Increased global connectivity and population movement as well as climate change affect the global distribution of both dengue vectors and the virus, facilitating the spread of dengue to new geographic areas. Weather is an important factor determining mosquito behaviour and effectiveness of dengue virus transmission. Dengue epidemic potential depends on vectorial capacity of Aedes mosquitoes, which depend on climate, such as, temperature and diurnal temperature range. This study aims at identifying high-risk areas and high-risk time windows in Europe based on temperature, in order for timely vector surveillance and control.

    Methods: Relative vectorial capacity (rVc) was used to estimate dengue epidemic potential. Using historical and projected temperature data over two centuries (1901–2099) and temperature dependent vector parameters for Aedes vectors, rVc was calculated for 10 selected European cities from Stockholm in the North to Malaga in the South.

    Results: Compared to dengue endemic areas, rVc in Europe was lower and showed more prominent seasonality. The peak and width of the seasonal windows in rVc were generally higher in the South than the North. Currently, only South and Central-East Europe and the summer season corresponds to rVc that is over the threshold for possible dengue transmission. By the end of this century, in the best case scenario, all the Central and Southern European cities would be at risk for dengue transmission during the warmer months; in the worst case scenario, this risk would extend to Northern European to include Stockholm if dengue vectors were established and virus introduced.

    Conclusion: As travel and globalization become more frequent channels for dengue vector and virus introduction, Europe may face the reality of more frequent dengue outbreaks in their warmer months. Madeira's outbreak in 2012 underlines this concern. The future's high risk area and time window depend sensitively on climate scenarios. Therefore, it is important to emphasize climate change mitigation and enhance vector surveillance and control in Europe.

    Acknowledgement: This research was funded by the European Union 7th Framework Programme through 'DengueTools' (www.denguetools.net).

    Disclosure: Nothing to disclose.

  • 5.
    Liu-Helmersson, Jing
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Quam, Mikkel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Ebi, Kristie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. University of Washington, Seattle, Washington, USA.
    Massad, Eduardo
    School of Medicine, University of Sao Paulo, Brazil.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Climate change and Aedes vectors: 21st century projections for dengue transmission in Europe2016In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 7, p. 267-277Article in journal (Refereed)
    Abstract [en]

    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.

  • 6.
    Liu-Helmersson, Jing
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health. Heidelberg University Medical School, Institute of Public Health, Heidelberg, Germany.
    Sewe, Maquins
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Sustainable Health.
    Brännström, Åke
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Evolution and Ecology Program, International Institute for Applied Systems Analysis, Laxenburg, Austria.
    Climate change may enable Aedes aegypti infestation in major European cities by 21002019In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 172, p. 693-699Article in journal (Refereed)
    Abstract [en]

    Background: Climate change allows Aedes aegyptito 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 aidin 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.

  • 7.
    Liu-Helmersson, Jing
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Sewe, Maquins
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Brännström, Å
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Predictions on the global abundance of Aedes aegypti vector population based on climate, human population and GDPIn: Article in journal (Refereed)
  • 8.
    Liu-Helmersson, Jing
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Vectorial capacity of Aedes aegypti: Effects of temperature and implications for global dengue epidemic potential2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 3, article id e89783Article in journal (Refereed)
    Abstract [en]

    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.

  • 9. Massad, Eduardo
    et al.
    Amaku, Marcos
    Coutinho, Francisco Antonio Bezerra
    Struchiner, Claudio José
    Burattini, Marcelo Nascimento
    Khan, Kamran
    Liu-Helmersson, Jing
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Kraemer, Moritz U. G.
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Institute of Public Health, University of Heidelberg, Germany; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
    Estimating the probability of dengue virus introduction and secondary autochthonous cases in Europe2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, no 1, article id 4629Article in journal (Refereed)
    Abstract [en]

    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.

  • 10.
    Quam, Mikkel B
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Liu-Helmersson, Jing
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Massad, E
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore City, Singapore.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Madeira's dengue outbreak in 2012: could it happen again in the near future?2015In: Tropical medicine & international health, ISSN 1360-2276, E-ISSN 1365-3156, Vol. 20, no Suppl. 1, p. 408-409Article in journal (Other academic)
    Abstract [en]

    Introduction: A dengue outbreak in 2012 having 2000 + reported cases, followed vector introduction to the Portuguese island of Madeira in 2005. We describe contributing factors for the 2012 outbreak through modeling of temperature dependent vectorial capacity, meteorological observations of environmental factors pertinent to vector lifecycle, and dynamics of travellers arriving from dengue endemic areas. In combination with reported vector and human surveillance, the temporal onset of the 2012 outbreak and factors setting 2012 apart from other years were used to generate a predictive model for potential re- emergence of dengue in Madeira.

    Methods: Relative Vectorial capacity (rVC) was calculated with previously published methods for Madeira (Island) and Funchal (City) from 2005 to 2014 based on both remotely sensed satellite data and observation stations. We also estimated potentially imported dengue infections using previously published methods. Epidemiological features of the 2012 outbreak combined with generated data to inform a predictive model. Projected travel and seasonal weather forecasting inputs for the predictive model described the dengue importation-driven transmission likelihood for Madeira in 2015.

    Results: Longitudinal comparisons of available data were displayed simultaneously to show periods of greatest potential for dengue emergence in Madeira, historically. The modeled outputs especially during the months before the outbreak provide more precise quantification and visualization of the temporal coincidence, which may have primed Madeira for emergence of dengue in late summer 2012. When seasonal forecast information is applied to the historically informed model for spring and summer 2015, potential for local dengue

    transmission in Madeira was determined. Conclusions Local transmission of dengue in Madeira may re occur given the environmental envelope and continuous importation of the dengue virus via travelers, even with strengthened vector control efforts; however, the severity of the 2012 outbreak will hopefully remain the highest. Our results clearly display the coalescence of multiple factors necessary for initial emergence of a dengue epidemic in a naïve population. Descriptive modeling of a known outbreak can better inform the development of predictive modeling of dengue emergence in Madeira and other areas of Europe.

    Acknowledgment: European Union 7th Framework Programme through DengueTools (www.denguetools.net) funded this research.

    Disclosure: Nothing to disclose.

  • 11.
    Quam, Mikkel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Sessions, O
    Liu-Helmersson, Jing
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Dissecting the origin of the 2014 dengue outbreak in Japan2015In: Tropical medicine & international health, ISSN 1360-2276, E-ISSN 1365-3156, Vol. 20, no Suppl. 1, p. 408-408Article in journal (Other academic)
    Abstract [en]

    Introduction: Endemic in at least 100 countries, dengue is currently regarded as world's most important mosquito borne viral disease. While most of the disease burden is limited to areas with tropical and sub-tropical climates, evidence suggests that temperate areas may be increasingly at risk as the geographic distribution of relevant vectors expands. Japan, a country with a temperate climate, reported the first major dengue outbreak in 2014. We examined the factors that may have facilitated the dengue outbreak in Tokyo during 2014.

    Methods: Multiple sequence alignment of the dengue virus 1 (DENV1) sequence from the 2014 dengue outbreak in Tokyo was carried out using a fast Fourier transformation method in MAFFT v6.940b. We collected the Japan National Tourism Organization’s data on inbound travelers between January and September 2014 from dengue endemic countries in Asia to Japan. Daily observations of temperature (minimum, maximum, and mean) and precipitation were obtained from the MIDAS dataset for Tokyo. We calculated the relative vectorial capacity (rVc) for Aedes vectors to quantify the dengue epidemic potential based on temperature dependent parameters, by applying a modified Ross-McDonald model.

    Findings: Tourist arrivals into Japan in 2014 coincided by 70% with its warm summer months suitable for dengue transmission, The phylogenetic similarity of DENV-1 isolated from the 2014 outbreak in Japan with viruses from China, Indonesia, Singapore, and Vietnam renders any of these four countries a likely source of importation. Several conducive climate factors converged preceding and during the time of the dengue outbreak in Tokyo, August until October 2014. Climate conditions, in particular mean temperature and precipitation, were favorable for the amplification of Aedes vectors. Furthermore, the ability for the vector to transmit dengue, as measured by the relative vectorial capacity, was highest at the time of the 2014 outbreak.

    Conclusions: Taking into account the travel volume into Japan, China appears the most probable source of dengue virus introduction that triggered Tokyo's outbreak. Despite Japan's temperate climate, dengue epidemic potential already exists. Under scenarios of changing climate and increasing regional travel, Japan will likely face more dengue outbreaks in the future.

    Acknowledgements: The study was financially supported by the European Union's Seventh Framework Programme- DengueTools (www.denguetools.net).

    Disclosure: Nothing to disclose.

  • 12.
    Rocklöv, Joacim
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Quam, Mikkel Brandon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Sudre, Bertrand
    German, Matthew
    Kraemer, Moritz U.G.
    Brady, Oliver
    Bogoch, Isaac I.
    Liu-Helmersson, Jing
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
    Semenza, Jan C.
    Ong, Mark
    Aaslav, Kaja Kaasik
    Khan, Kamran
    Assessing Seasonal Risks for the Introduction and Mosquito-borne Spread of Zika Virus in Europe2016In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 9, p. 250-256Article in journal (Refereed)
    Abstract [en]

    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.

  • 13. Sang, Shaowei
    et al.
    Liu-Helmersson, Jing
    Umeå University, Faculty of Medicine, Department of Epidemiology and Global Health.
    Quam, Mikkel B. M.
    Zhou, Hongning
    Guo, Xiaofang
    Wu, Haixia
    Liu, Qiyong
    The evolutionary dynamics of DENV 4 genotype I over a 60-year period2019In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 13, no 7, article id e0007592Article in journal (Refereed)
    Abstract [en]

    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) x 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. Author summary Dengue virus (DENV) can be classified into four serotypes, DENV 1, 2, 3 and 4. Although DENV 4 is the first dengue serotype to diverge in phylogenetic analyses of the genus Flavivirus, this serotype occurs at a low prevalence worldwide and spreads the least rapidly. Similar to other serotypes, DENV 4 can also cause severe dengue (SD) disease manifestations, such as dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS). To date, no study has investigated the epidemiology and dynamics of DENV 4 genotype I comprehensively. In this study, we seek to address this gap. Our study shows that the distribution of DENV 4-I is mainly restricted to Southeast Asia and the Indian subcontinent. The most recent spread of DENV 4-I likely originated from Southeast Asia-initially circulating in the Philippines, then Thailand and later on the Indian subcontinent. Viruses evolved in situ in Southeast Asia and the Indian subcontinent, respectively. Although DENV 4-I occasionally spread elsewhere, this genotype did not become widely established. The overall evolution rate of DENV 4-I was comparable with that of DENV 2-4. The nucleotide sequences indicates that the demographic history of DENV 4-I fluctuated with peaks apparent during parts of the 1980s and 2000s. Although a weak positive selection existed in Clade III -predominately in Vietnam, purifying selection dominated the E-gene evolution of DENV 4-I.

  • 14.
    Wilder-Smith, Annelies
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
    Quam, Mikkel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Sessions, O.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Liu-Helmersson, Jing
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Franco, L.
    Khan, K.
    The 2012 dengue outbreak in Madeira: exploring the origins2014In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 19, no 8, p. 20718-Article in journal (Refereed)
    Abstract [en]

    In 2012, Madeira reported its first major outbreak of dengue. To identify the origin of the imported dengue virus, we investigated the interconnectivity via air travel between dengue-endemic countries and Madeira, and compared available sequences against GenBank. There were 22,948 air travellers to Madeira in 2012, originating from twenty-nine dengue-endemic countries; 89.6% of these international travellers originated from Venezuela and Brazil. We developed an importation index that takes into account both travel volume and the extent of dengue incidence in the country of origin. Venezuela and Brazil had by far the highest importation indices compared with all other dengue-endemic countries. The importation index for Venezuela was twice as high as that for Brazil. When taking into account seasonality in the months preceding the onset of the Madeira outbreak, this index was even seven times higher for Venezuela than for Brazil during this time. Dengue sequencing shows that the virus responsible for the Madeira outbreak was most closely related to viruses circulating in Venezuela, Brazil and Columbia. Applying the importation index, Venezuela was identified as the most likely origin of importation of dengue virus via travellers to Madeira. We propose that the importation index is a new additional tool that can help to identify and anticipate the most probable country of origin for importation of dengue into currently non-endemic countries.

  • 15. Zhang, Xiangwei
    et al.
    Wang, Yang
    Li, Cheng
    Helmersson, Jing
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Jiang, Yuanzhu
    Ma, Guoyuan
    Wang, Guanghui
    Dong, Wei
    Sang, Shaowei
    Du, Jiajun
    The prognostic value of tumor length to resectable esophageal squamous cell carcinoma: a retrospective study2017In: PeerJ, ISSN 2167-8359, E-ISSN 2167-8359, Vol. 5, article id e2943Article in journal (Refereed)
    Abstract [en]

    Background: The current TNM classification system does not consider tumor length for patients with esophageal carcinoma (EC). This study explored the effect of tumor length, in addition to tumor depth and lymph node involvement, on survival in patients with esophageal squamous cell carcinoma (ESCC).

    Methods: A total of 498 ESCC patients who underwent surgical resection as the primary treatment were selected in the retrospective study. Pathological details were collected, which included tumor type, TNM stage, differentiation. Other collected information were: the types of esophageal resection, ABO blood group, family history and demographic and lifestyle factors. A time-dependent receiver operating characteristic (ROC) curve and a regression tree for survival were used to identify the cut-off point of tumor length, which was 3 cm. Univariate and multivariate Cox proportional hazard regression models were used to identify the prognostic factors to ESCC.

    Results & Discussion: The 1-, 3-, 5-year overall survival rates were found to be 82.5%, 55.6%, and 35.1%, respectively. Patients who had larger tumor length (>3 cm) had a higher risk for death than the rest patients. From the univariate Cox proportional hazards regression model, the overall survival rate was significantly influenced by the depth of the tumor and lymph node involvement (either as dummy or continuous variables), Sex, and tumor length. Using these four variables in the multivariate Cox proportional hazard regression model, we found that the overall survival was significantly influenced by all variables except Sex. Therefore, in addition to the depth of the tumor and lymph node involvement (as either dummy or continuous variables), the tumor length is also an independent prognostic factor for ESCC. The overall survival rate was higher in a group with smaller tumor length (≤3 cm) than those patients with larger tumor length (>3 cm), no matter what the tumor stage was.

    Conclusion: The tumor length was found to be an important prognostic factor for ESCC patients without receiving neoadjuvant therapy. The modification of EC staging system may consider tumor length to better predict ESCC survival and identify higher risk patients for postoperative therapy.

  • 16. Zhang, Xiangwei
    et al.
    Wang, Yang
    Qu, Pengfei
    Liu-Helmersson, Jing
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Zhao, Linping
    Zhang, Lin
    Sang, Shaowei
    The Prognostic Value of Tumor Length for Cause-Specific Mortality in Resectable Esophageal Cancer.2018In: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 106, no 4, p. 1038-1046Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The current esophageal cancer AJCC-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 mortality.

    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 - 2014). Using 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 mortality was analyzed.

    RESULTS: 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-T3 classifications who had larger tumor size showed a larger probability of cancer-specific mortality. The multivariate Cox model showed that tumor size was significantly associated with an increase in cancer-specific mortality in T1 (2.15, 95% CI [1.72, 2.69]) and T2 (1.31, 95% CI [1.06, 1.62]), but marginally significantly in T3 (1.12, 95% CI [1.00, 1.27]) and insignificantly in T4 classification (p > 0.1). Similar results were found 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-T2 classification. Based on esophageal cancer-specific mortality our study is the first to explore the prognostic cutoff point of tumor size by T classification.

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