Isolation and characterization of dengue virus serotype 2 from the large dengue outbreak in Guangdong,China in 2014

Dengue has been well recognized as a global public health threat,but only sporadic epidemics and imported cases were reported in recent decades in China.Since July 2014,an unexpected large dengue outbreak has occurred in Guangdong province,China,resulting in more than 40000 patients including six deaths.To clarify and characterize the causative agent of this outbreak,the acute phase serum from a patient diagnosed with severe dengue was subjected to virus isolation and high-throughput sequencing(HTS).Traditional real-time RT-PCR and HTS with Ion Torrent PGM detected the presence of dengue virus serotype 2(DENV-2).A clinical DENV-2 isolate GZ05/2014 was obtained by culturing the patient serum in mosquito C6/36 cells.The complete genome of GZ05/2014 was determined and deposited in Gen Bank under the access number KP012546.Phylogenetic analysis based on the complete envelope gene showed that the newly DENV-2 isolate belonged to Cosmopolitan genotype and clustered closely with other Guangdong strains isolated in the past decade.No amino acid mutations that are obviously known to increase virulence or replication were identified throughout the genome of GZ05/2014.The high homology of Guangdong DENV-2 strains indicated the possibility of establishment of local DENV-2 circulation in Guangdong,China.These results help clarify the origin of this epidemic and predict the future status of dengue in China.     

Quantifying the spatial dimension of dengue virus epidemic spread within a tropical urban environment

Background

Dengue infection spread in naive populations occurs in an explosive and widespread fashion primarily due to the absence of population herd immunity, the population dynamics and dispersal of Ae. aegypti, and the movement of individuals within the urban space. Knowledge on the relative contribution of such factors to the spatial dimension of dengue virus spread has been limited. In the present study we analyzed the spatio-temporal pattern of a large dengue virus-2 (DENV-2) outbreak that affected the Australian city of Cairns (north Queensland) in 2003, quantified the relationship between dengue transmission and distance to the epidemic''s index case (IC), evaluated the effects of indoor residual spraying (IRS) on the odds of dengue infection, and generated recommendations for city-wide dengue surveillance and control.

Methods and Findings

We retrospectively analyzed data from 383 DENV-2 confirmed cases and 1,163 IRS applications performed during the 25-week epidemic period. Spatial (local k-function, angular wavelets) and space-time (Knox test) analyses quantified the intensity and directionality of clustering of dengue cases, whereas a semi-parametric Bayesian space-time regression assessed the impact of IRS and spatial autocorrelation in the odds of weekly dengue infection. About 63% of the cases clustered up to 800 m around the IC''s house. Most cases were distributed in the NW-SE axis as a consequence of the spatial arrangement of blocks within the city and, possibly, the prevailing winds. Space-time analysis showed that DENV-2 infection spread rapidly, generating 18 clusters (comprising 65% of all cases), and that these clusters varied in extent as a function of their distance to the IC''s residence. IRS applications had a significant protective effect in the further occurrence of dengue cases, but only when they reached coverage of 60% or more of the neighboring premises of a house.

Conclusion

By applying sound statistical analysis to a very detailed dataset from one of the largest outbreaks that affected the city of Cairns in recent times, we not only described the spread of dengue virus with high detail but also quantified the spatio-temporal dimension of dengue virus transmission within this complex urban environment. In areas susceptible to non-periodic dengue epidemics, effective disease prevention and control would depend on the prompt response to introduced cases. We foresee that some of the results and recommendations derived from our study may also be applicable to other areas currently affected or potentially subject to dengue epidemics.     

华南地区温度变化及其对登革热传播时间的影响

根据华南地区110个气象站1961—2012年的逐日气温资料,以及Reg CM4区域气候模式RCP情景下未来逐日气温预估数据,采用Ross-Macdonald疾病传播动力学模型、线性趋势分析、累积距平、五日滑动平均等方法和Arc GIS技术,研究了华南地区温度变化及其对登革热传播时间的影响。结果表明:21℃可作为适宜登革热传播的下限温度指标,1961—2012年华南地区年平均气温以0.14℃·10 a-1的速率显著上升,1997年发生了突变;与1981—2010年平均值相比,2020s、2050s和2080s华南地区温度增幅在RCP4.5情景下分别为0.8、1.3和1.7℃,RCP8.5情景下分别为0.9、1.7和2.9℃;气温突变后(1997—2012年)全年适于登革热传播的日数、终年流行区面积分别较突变前(1961—1996年)增加了10 d和408 km2;与1997—2012年平均值相比,2020s、2050s和2080s全年适于登革热传播的日数在RCP4.5情景下分别增加了10、15和20 d,RCP8.5情景下分别增加了15、25和40 d,终年流行区面积在RCP4.5情景下分别增加了3962、5436和8260 km2,RCP8.5情景下分别增加了4536、8780和20680 km2。     

Dynamics of the 2006/2007 dengue outbreak in Brazil

We analyzed dengue incidence in the period between October 2006-July 2007 of 146 cities around the country were Larval Index Rapid Assay (LIRA) surveillance was carried out in October 2006. Of these, we chosen 61 cities that had 500 or more cases reported during this period. We calculated the incidence coefficient, the force of infection (lambda) and the basic reproduction number (R0) of dengue in those 61 cities and correlated those variables with the LIRA. We concluded that lambda and R0 are more associated with the number of cases than LIRA. In addition, the average R0 for the 2006/2007 dengue season was almost as high as that calculated for the 2001/2002 season, the worst in Brazilian history.     

The effect of weather and climate on dengue outbreak risk in Peru, 2000-2018: A time-series analysis

BackgroundDengue fever is the most common arboviral disease in humans, with an estimated 50-100 million annual infections worldwide. Dengue fever cases have increased substantially in the past four decades, driven largely by anthropogenic factors including climate change. More than half the population of Peru is at risk of dengue infection and due to its geography, Peru is also particularly sensitive to the effects of El Niño Southern Oscillation (ENSO). Determining the effect of ENSO on the risk for dengue outbreaks is of particular public health relevance and may also be applicable to other Aedes-vectored viruses.MethodsWe conducted a time-series analysis at the level of the district-month, using surveillance data collected from January 2000 to September 2018 from all districts with a mean elevation suitable to survival of the mosquito vector (<2,500m), and ENSO and weather data from publicly-available datasets maintained by national and international agencies. We took a Bayesian hierarchical modeling approach to address correlation in space, and B-splines with four knots per year to address correlation in time. We furthermore conducted subgroup analyses by season and natural region.ResultsWe detected a positive and significant effect of temperature (°C, RR 1.14, 95% CI 1.13, 1.15, adjusted for precipitation) and ENSO (ICEN index: RR 1.17, 95% CI 1.15, 1.20; ONI index: RR 1.04, 95% CI 1.02, 1.07) on outbreak risk, but no evidence of a strong effect for precipitation after adjustment for temperature. Both natural region and season were found to be significant effect modifiers of the ENSO-dengue effect, with the effect of ENSO being stronger in the summer and the Selva Alta and Costa regions, compared with winter and Selva Baja and Sierra regions.ConclusionsOur results provide strong evidence that temperature and ENSO have significant effects on dengue outbreaks in Peru, however these results interact with region and season, and are stronger for local ENSO impacts than remote ENSO impacts. These findings support optimization of a dengue early warning system based on local weather and climate monitoring, including where and when to deploy such a system and parameterization of ENSO events, and provide high-precision effect estimates for future climate and dengue modeling efforts.     

Epidemiology and vector efficiency during a dengue fever outbreak in Cixi,Zhejiang Province,China

An emigrant worker returning from Southeast Asia triggered the outbreak of a DF epidemic in Zhejiang province, China, in October, 2004. Eighty‐three cases, mainly young and middle‐aged people between 20 and 50 (78.3%), were reported in the area of Cixi. There were no obvious occupational patterns. The majority of cases were female, with a sex ratio of 1:1.86 (m:f). The dengue virus (DENV) strains from the epidemic area were isolated and identified as DENV‐1, which belongs to Asian strain 1. According to the epidemiological investigation, the incidence of DF had no relationship to temperature, humidity, or precipitation, and the Breteau index of larvae showed a clear relationship only with the House Index and Container Index. Recent dengue problems in the town have been associated with the complex social factors and hygienic conditions for endemic villagers and immigrant workers. Some hygienic measures should be taken by the local government to reduce the risk of mosquito‐borne disease. These measures should aim to eliminate the breeding sites of the vector Aedes albopictus in indoor and outdoor containers filled with rainwater and thus reducing the risk of DF transmission.     

Molecular epidemiology demonstrates that imported and local strains circulated during the 2014 dengue outbreak in Guangzhou,China

The dengue virus(DENV) is a vital global public health issue. The 2014 dengue epidemic in Guangzhou, China, caused approximately 40,000 cases of infection and five deaths. We carried out a comprehensive investigation aimed at identifying the transmission sources in this dengue epidemic. To analyze the phylogenetics of the 2014 dengue strains, the envelope(E) gene sequences from 17 viral strains isolated from 168 dengue patient serum samples were sequenced and a phylogenetic tree was reconstructed. All 17 strains were serotype Ⅰ strains, including 8genotype Ⅰ and 9 genotype V strains. Additionally, 6 genotype Ⅰ strains that were probably introduced to China from Thailand before 2009 were widely transmitted in the 2013 and 2014 epidemics, and they continued to circulate until 2015, with one affinis strain being found in Singapore. The other 2 genotype Ⅰ strains were introduced from the Malaya Peninsula in 2014. The transmission source of the 9 genotype Ⅴ strains was from Malaysia in 2014. DENVs of different serotypes and genotypes co-circulated in the 2014 dengue outbreak in Guangzhou. Moreover, not only had DENV been imported to Guangzhou, but it had also been gradually exported, as the viruses exhibited an enzootic transmission cycle in Guangzhou.     

Assessing potential countermeasures against the dengue epidemic in non-tropical urban cities

Background

Dengue is a common mosquito-borne viral disease epidemic especially in tropical and sub-tropical regions where water sanitation is not substantially controlled. However, dengue epidemics sometimes occur in non-tropical urban cities with substantial water sanitary control. Using a mathematical model, we investigate what conditions can be important for a dengue epidemic to occur in an urban city such as Tokyo, where vectors are active only in summer and there are little number of vectors around hosts.

Methods

The model, which is a modified Ross-Macdonald model, consists of two sets of host-vector compartments. The two sets correspond to high-risk and low-risk areas, and only hosts can move between them. Assuming that mosquitoes have constant activity for only 90 days, we assess five potential countermeasures: (1) restricted movement between the two areas, (2) insecticide application, (3) use of repellents, (4) vector control, and (5) isolation of the infected.

Results

The basic reproduction number R ₀ and the cumulative number of infected hosts for 90 days are evaluated for each of the five countermeasures. In the cases of Measures 2–5, the cumulative number of the infected for 90 days can be reduced substantially for small R ₀ even if R ₀>1. Although R ₀ for Measure 1 monotonically decreases with the mobility rates, the cumulative number of the infected for 90 days has a maximum at a moderate mobility rate. If the mobility rate is sufficiently small, the restricted movement effectively increases the number density of vectors in the high-risk area, and the epidemic starts earlier in the high-risk area than in the low-risk one, while the growth of infections is slow.

Conclusions

Measures 2–5 are more or less effective. However, Measure 1 can have the opposite effect, depending on the mobility rates. The restricted movement results in the formation of a kind of core population, which can promote the epidemic in the entire population.

     

Evolutionary relationships of endemic/epidemic and sylvatic dengue viruses

Endemic/epidemic dengue viruses (DEN) that are transmitted among humans by the mosquito vectors Aedes aegypti and Aedes albopictus are hypothesized to have evolved from sylvatic DEN strains that are transmitted among nonhuman primates in West Africa and Malaysia by other Aedes mosquitoes. We tested this hypothesis with phylogenetic studies using envelope protein gene sequences of both endemic/epidemic and sylvatic strains. The basal position of sylvatic lineages of DEN-1, -2, and -4 suggested that the endemic/epidemic lineages of these three DEN serotypes evolved independently from sylvatic progenitors. Time estimates for evolution of the endemic/epidemic forms ranged from 100 to 1,500 years ago, and the evolution of endemic/epidemic forms represents relatively recent events in the history of DEN evolution. Analysis of envelope protein amino acid changes predicted to have accompanied endemic/epidemic emergence suggested a role for domain III in adaptation to new mosquito and/or human hosts.     

Polygenic evolution drives species divergence and climate adaptation in corals

Closely related species often show substantial differences in ecological traits that allow them to occupy different environmental niches. For few of these systems is it clear what the genomic basis of adaptation is and whether a few loci of major effect or many genome‐wide differences drive species divergence. Four cryptic species of the tabletop coral Acropora hyacinthus are broadly sympatric in American Samoa; here we show that two common species have differences in key environmental traits such as microhabitat distributions and thermal stress tolerance. We compared gene expression patterns and genetic polymorphism between these two species using RNA‐Seq. The vast majority of polymorphisms are shared between species, but the two species show widespread differences in allele frequencies and gene expression, and tend to host different symbiont types. We find that changes in gene expression are related to changes in the frequencies of many gene regulatory variants, but that many of these differences are consistent with the action of genetic drift. However, we observe greater genetic divergence between species in amino acid replacement polymorphisms compared to synonymous variants. These findings suggest that polygenic evolution plays a major role in driving species differences in ecology and resilience to climate change.     

From re-emergence to hyperendemicity: the natural history of the dengue epidemic in Brazil

Background

Dengue virus (DENV) was reintroduced into Brazil in 1986 and by 1995 it had spread throughout the country. In 2007 the number of dengue hemorrhagic fever (DHF) cases more than doubled and a shift in the age distribution was reported. While previously the majority of DHF cases occurred among adults, in 2007 53% of cases occurred in children under 15 years old. The reasons for this shift have not been determined.

Methods and Findings

Age stratified cross-sectional seroepidemiologic survey conducted in Recife, Brazil in 2006. Serostatus was determined by ELISA based detection of Dengue IgG. We estimated time-constant and time-varying forces of infection of DENV between 1986 and 2006. We used discrete-time simulation to estimate the accumulation of monotypic and multitypic immunity over time in a population previously completely susceptible to DENV. We projected the age distribution of population immunity to dengue assuming similar hazards of infection in future years. The overall prevalence of DENV IgG was 0.80 (n = 1427). The time-constant force of infection for the period was estimated to be 0.052 (95% CI 0.041, 0.063), corresponding to 5.2% of susceptible individuals becoming infected each year by each serotype. Simulations show that as time since re-emergence of dengue goes by, multitypic immunity accumulates in adults while an increasing proportion of susceptible individuals and those with monotypic immunity are among young age groups. The median age of those monotypically immune can be expected to shift from 24 years, 10 years after introduction, to 13 years, 50 years after introduction. Of those monotypically immune, the proportion under 15 years old shifts from 27% to 58%. These results are consistent with the dengue notification records from the same region since 1995.

Interpretation

Assuming that persons who have been monotypically exposed are at highest risk for severe dengue, the shift towards younger patient ages observed in Brazil can be partially explained by the accumulation of multitypic immunity against DENV-1, 2, and 3 in older age groups, 22 years after the re-introduction of these viruses. Serotype specific seroepidemiologic studies are necessary to accurately estimate the serotype specific forces of infection.     

Resonance of the epidemic threshold in a periodic environment

Resonance between some natural period of an endemic disease and a seasonal periodic contact rate has been the subject of intensive study. This paper does not focus on resonance for endemic diseases but on resonance for emerging diseases. Periodicity can have an important impact on the initial growth rate and therefore on the epidemic threshold. Resonance occurs when the Euler-Lotka equation has a complex root with an imaginary part (i.e., a natural frequency) close to the angular frequency of the contact rate and a real part not too far from the Malthusian parameter. This is a kind of continuous-time analogue of work by Tuljapurkar on discrete-time population models, which in turn was motivated by the work by Coale on continuous-time demographic models with a periodic birth. We illustrate this resonance phenomenon on several simple epidemic models with contacts varying periodically on a weekly basis, and explain some surprising differences, e.g., between a periodic SEIR model with an exponentially distributed latency and the same model but with a fixed latency.     

气候变暖可能对东北三省农业生态环境的影响及其对策

随着未来气候变暖,我国东北三省农业生态环境可能发生较大的变化,其变化趋势为,热量条件变好,作物生育期延长,冷害频率降低,积雪期缩短,湿润条件变差,干旱频率增大,蒸发量增加。未来气候变暖,若平均气温升高2℃,那时东北三省粮食产量可增加36%左右,农业地带将大幅度地向北推移,并且提出相应的农业对策。     

Monitoring and prediction of an epidemic outbreak using syndromic observations

The paper presents a method for syndromic surveillance of an epidemic outbreak due to an emerging disease, formulated in the context of stochastic nonlinear filtering. The dynamics of the epidemic is modeled using a stochastic compartmental epidemiological model with inhomogeneous mixing. The syndromic (typically non-medical) observations of the number of infected people (e.g. visits to pharmacies, sale of certain products, absenteeism from work/study, etc.) are assumed available for monitoring and prediction of the epidemic. The state of the epidemic, including the number of infected people and the unknown parameters of the model, are estimated via a particle filter. The numerical results indicate that the proposed framework can provide useful early prediction of the epidemic peak if the uncertainty in prior knowledge of model parameters is not excessive.     

Estimation of the reproduction number of dengue fever from spatial epidemic data

Dengue, a vector-borne disease, thrives in tropical and subtropical regions worldwide. A retrospective analysis of the 2002 dengue epidemic in Colima located on the Mexican central Pacific coast is carried out. We estimate the reproduction number from spatial epidemic data at the level of municipalities using two different methods: (1) Using a standard dengue epidemic model and assuming pure exponential initial epidemic growth and (2) Fitting a more realistic epidemic model to the initial phase of the dengue epidemic curve. Using Method I, we estimate an overall mean reproduction number of 3.09 (95% CI: 2.34,3.84) as well as local reproduction numbers whose values range from 1.24 (1.15,1.33) to 4.22 (2.90,5.54). Using Method II, the overall mean reproduction number is estimated to be 2.0 (1.75,2.23) and local reproduction numbers ranging from 0.49 (0.0,1.0) to 3.30 (1.63,4.97). Method I systematically overestimates the reproduction number relative to the refined Method II, and hence it would overestimate the intensity of interventions required for containment. Moreover, optimal intervention with defined resources demands different levels of locally tailored mitigation. Local epidemic peaks occur between the 24th and 35th week of the year, and correlate positively with the final local epidemic sizes (rho=0.92, P-value<0.001). Moreover, final local epidemic sizes are found to be linearly related to the local population size (P-value<0.001). This observation supports a roughly constant number of female mosquitoes per person across urban and rural regions.     

Molecular and epidemiologic characteristics of HIV-infection outbreak in the Irkutsk region

The genetic analysis of the variants of human immunodeficiency virus of type 1 (HIV-I) circulating among drug addicts in the Irkutsk region was carried out. The results of serological tests and comparative evaluation of electrophoretic mobility of heteroduplexes (HMA) revealed that all 74 samples under study belonged to subtype A. Genetic differences between these viruses did not exceed 2%. Thus, it was the variant of subtype A prevalent in CIS countries which caused the outbreak of HIV infection among drug addicts in the Irkutsk region, but not viruses of subtypes B, C or A/E typical for this risk group in relatively nearby China.