High genetic diversity of the himalayan marmot relative to plague outbreaks in the Qinghai-Tibet Plateau, China.

Plague, as an ancient zoonotic disease caused by Yersinia pestis, has brought great disasters. The natural plague focus of Marmota himalayana in the Qinghai-Tibet Plateau is the largest, which has been constantly active and the leading source of human plague in China for decades. Understanding the population genetics of M. himalayana and relating that information to the biogeographic distribution of Yersinia pestis and plague outbreaks are greatly beneficial for the knowledge of plague spillover and arecrucial for pandemic prevention. In the present research, we assessed the population genetics of M. himalayana. We carried out a comparative study of plague outbreaks and the population genetics of M. himalayana on the Qinghai-Tibet Plateau. We found that M. himalayana populations are divided into two main clusters located in the south and north of the Qinghai-Tibet Plateau. Fourteen DFR genomovars of Y. pestis were found and exhibited a significant region-specific distribution. Additionally, the increased genetic diversity of plague hosts is positively associated with human plague outbreaks. This insight gained can improve our understanding of biodiversity for pathogen spillover and provide municipally directed targets for One Health surveillance development, which will be an informative next step toward increased monitoring of M. himalayana dynamics.

Clinical and Dosimetric Risk Factors Associated With Radiation-Induced Lung Toxicities After Multiple Courses of Lung Stereotactic Body Radiation Therapy.

Purpose: Data are limited on radiation-induced lung toxicities (RILT) after multiple courses of lung stereotactic body radiation therapy (SBRT). We herein analyze a large cohort of patients to explore the clinical and dosimetric risk factors associated with RILT in such settings. Methods and Materials: A single institutional database of patients treated with multiple courses of lung SBRT between January 2014 and December 2019 was analyzed. Grade 2 or higher (G2+) RILT after the last course of SBRT was the primary endpoint. Composite plans were generated with advanced algorithms including deformable registration and equivalent dose adjustment. Logistic regression analyses were performed to examine correlations between patient or treatment factors including dosimetry and G2+ RILT. Risk stratification of patients and lung constraints based on acceptable normal tissue complication probability were calculated based on risk factors identified. Results: Among 110 eligible patients (56 female and 54 male), there were 64 synchronous (58.2%; defined as 2 courses of SBRT delivered within 30 days) and 46 metachronous (41.8%) courses of SBRT. The composite median lung V20, lung V5, and mean lung dose were 9.9% (interquartile range [IQR], 7.3%-12.4%), 32.2% (IQR, 25.5%-40.1%), and 7.0 Gy (IQR, 5.5 Gy-8.6 Gy), respectively. With a median follow-up of 21.1 months, 30 patients (27.3%) experienced G2+ RILT. Five patients (4.5%) developed G3 RILT, and 1 patient (0.9%) developed G4 RILT, and no patients developed G5 RILT. On multivariable regression analysis, female sex (odds ratio [OR], 4.35; 95% CI, 1.49%-14.3%; P = .01), synchronous SBRT (OR, 8.78; 95% CI, 2.27%-47.8%; P = .004), prior G2+ RILT (OR, 29.8; 95% CI, 2.93%-437%; P = .007) and higher composite lung V20 (OR, 1.18; 95% CI, 1.02%-1.38%; P = .030) were associated with significantly higher likelihood of G2+ RILT. Conclusions: Our data suggest an acceptable incidence of G2+ RILT after multiple courses of lung SBRT. Female sex, synchronous SBRT, prior G2+ RILT, and higher composite lung V20 may be risk factors for G2+ RILT.

The epidemiology and evolutionary dynamics of massive dengue outbreak in China, 2019.

Introduction: In 2019, China experienced massive dengue outbreaks with high incidence and expanded outbreak areas. The study aims to depict dengue's epidemiology and evolutionary dynamics in China and explore the possible origin of these outbreaks. Methods: Records of confirmed dengue cases in 2019 were obtained from the China Notifiable Disease Surveillance System. The sequences of complete envelope gene detected from the outbreak provinces in China in 2019 were retrieved from GenBank. Maximum Likelihood trees were constructed to genotype the viruses. The median-joining network was used to visualize fine-scale genetic relationships. Four methods were used to estimate the selective pressure. Results: A total of 22,688 dengue cases were reported, 71.4% of which were indigenous cases and 28.6% were imported cases (including from abroad and from other domestic provinces). The abroad cases were predominantly imported from Southeast Asia countries (94.6%), with Cambodia (3,234 cases, 58.9%), and Myanmar (1,097 cases, 20.0%) ranked as the top two. A total of 11 provinces with dengue outbreaks were identified in the central-south of China, of which Yunnan and Guangdong provinces had the highest number of imported and indigenous cases. The primary source of imported cases in Yunnan was from Myanmar, while in the other ten provinces, the majority of imported cases were from Cambodia. Guangdong, Yunnan and Guangxi provinces were China's primary sources of domestically imported cases. Phylogenetic analysis of the viruses in outbreak provinces revealed three genotypes: (I, IV, and V) in DENV 1, Cosmopolitan and Asian I genotypes in DENV 2, and two genotypes (I and III) in DENV 3. Some genotypes concurrently circulated in different outbreak provinces. Most of the viruses were clustered with those from Southeast Asia. Haplotype network analysis showed that Southeast Asia, possibly Cambodia and Thailand, was the respective origin of the viruses in clade 1 and 4 for DENV 1. Positive selection was detected at codon 386 in clade 1. Conclusion: Dengue importation from abroad, especially from Southeast Asia, resulted in the dengue epidemic in China in 2019. Domestic transmission between provinces and positive selection on virus evolution may contribute to the massive dengue outbreaks.

The patterns and driving forces of dengue invasions in China.

BACKGROUND: Global connectivity and environmental change pose continuous threats to dengue invasions from worldwide to China. However, the intrinsic relationship on introduction and outbreak risks of dengue driven by the landscape features are still unknown. This study aimed to map the patterns on source-sink relation of dengue cases and assess the driving forces for dengue invasions in China. METHODS: We identified the local and imported cases (2006-2020) and assembled the datasets on environmental conditions. The vector auto-regression model was applied to detect the cross-relations of source-sink patterns. We selected the major environmental drivers via the Boruta algorithm to assess the driving forces in dengue outbreak dynamics by applying generalized additive models. We reconstructed the internal connections among imported cases, local cases, and external environmental drivers using the structural equation modeling. RESULTS: From 2006 to 2020, 81,652 local dengue cases and 12,701 imported dengue cases in China were reported. The hotspots of dengue introductions and outbreaks were in southeast and southwest China, originating from South and Southeast Asia. Oversea-imported dengue cases, as the Granger-cause, were the initial driver of the dengue dynamic; the suitable local bio-socioecological environment is the fundamental factor for dengue epidemics. The Bio8 [odds ratio (OR) = 2.11, 95% confidence interval (CI): 1.67-2.68], Bio9 (OR = 291.62, 95% CI: 125.63-676.89), Bio15 (OR = 4.15, 95% CI: 3.30-5.24), normalized difference vegetation index in March (OR = 1.27, 95% CI: 1.06-1.51) and July (OR = 1.04, 95% CI: 1.00-1.07), and the imported cases are the major drivers of dengue local transmissions (OR = 4.79, 95% CI: 4.34-5.28). The intermediary effect of an index on population and economic development to local cases via the path of imported cases was detected in the dengue dynamic system. CONCLUSIONS: Dengue outbreaks in China are triggered by introductions of imported cases and boosted by landscape features and connectivity. Our research will contribute to developing nature-based solutions for dengue surveillance, mitigation, and control from a socio-ecological perspective based on invasion ecology theories to control and prevent future dengue invasion and localization.

Dengue Fever in Mainland China, 2005-2020: A Descriptive Analysis of Dengue Cases and Aedes Data.

Dengue fever occurs throughout mainland China, except in the Tibet Autonomous Region. During 2005-2020, there were 12,701 imported cases and 81,653 indigenous cases recorded. The indigenous cases were mainly clustered in Guangdong (74.0%) and Yunnan provinces (13.7%). Indigenous dengue fever is a seasonal illness in mainland China, manifesting predominantly in summer and autumn. Indigenous dengue fever cases tend to peak every 5years and have shown a substantial increase during the period 2005-2020. During the study period, indigenous dengue fever occurred more than ten times in each of the seven counties of Guangdong Province. Indigenous dengue fever has spread from low to high latitudes; that is, from the southwestern, southern, and southeastern areas to the central and northern regions, and from border ports and cities to rural areas. Aedes aegypti has become widespread in Yunnan Province but has diminished in Guangxi, Guangdong, and Hainan provinces in recent years. Aedes albopictus is distributed throughout mainland China, spanning 25 provinces and municipalities. To maintain effective public health prevention and control, it is important to monitor dengue occurrence, provide dengue classification guidance, and ensure sustainable vector management of Aedes.

Horizontal Transmission of Cytomegalovirus in a Rhesus Model Despite High-Level, Vaccine-Elicited Neutralizing Antibody and T-Cell Responses.

The development of a vaccine to prevent congenital human cytomegalovirus (HCMV) disease is a public health priority. We tested rhesus CMV (RhCMV) prototypes of HCMV vaccine candidates in a seronegative macaque oral challenge model. Immunogens included a recombinant pentameric complex (PC; gH/gL/pUL128/pUL130/pUL131A), a postfusion gB ectodomain, and a DNA plasmid that encodes pp65-2. Immunization with QS21-adjuvanted PC alone or with the other immunogens elicited neutralizing titers comparable to those elicited by RhCMV infection. Similarly, immunization with all 3 immunogens elicited pp65-specific cytotoxic T-cell responses comparable to those elicited by RhCMV infection. RhCMV readily infected immunized animals and was detected in saliva, blood, and urine after challenge in quantities similar to those in placebo-immunized animals. If HCMV evades vaccine-elicited immunity in humans as RhCMV evaded immunity in macaques, a HCMV vaccine must elicit immunity superior to, or different from, that elicited by the prototype RhCMV vaccine to block horizontal transmission.

A Descriptive Analysis of Human Rabies in Mainland China, 2005-2020.

Epidemiological characteristics of human rabies in mainland China, 2005-2020 were analyzed to evaluate the effect of rabies control in China in recent years. A total of 24,319 human rabies cases were recorded in 2097 counties in 321 cities of 31 provinces in mainland China. Only 202 cases, located in 143 counties, were recorded in 2020, compared with 3305 cases in 992 counties in 2007; however, rabies was still relatively severe in Hunan Province even in 2020. Peak periods occurred in July-November; August was often the month with the most cases. Guizhou, Hunan, Guangdong, and Guangxi Provinces, in the central and southern regions, accounted for 50.0% of the cases in 2005-2020. Cases occurred almost exclusively in rural areas with 96.7% versus 3.3% in urban areas. A paradoxical relative expansion from southern, eastern, and central towards southwestern, northwestern, northern, and northeastern regions was observed along with the overall reduction of cases. Some regions witnessed complete elimination. The male-to-female ratio was 2.33:1; 66.8% of all cases were reported in the 0-10 (13.8%) and 41-70 (53.0%) age groups. Farmers (68.3%), followed by students (12.2), and diaspora children (6.5%) were most frequently involved. Our results provide objective information for the improvement of rabies prevention and control efforts. This will aid policymakers in China and elsewhere achieve the "Zero human deaths from dog-mediated rabies by 2030" global goal.

Pathogenesis of Wild-Type-Like Rhesus Cytomegalovirus Strains following Oral Exposure of Immune-Competent Rhesus Macaques.

Rhesus cytomegalovirus (RhCMV) infection of rhesus macaques (Macaca mulatta) is a valuable nonhuman primate model of human CMV (HCMV) persistence and pathogenesis. In vivo studies predominantly use tissue culture-adapted variants of RhCMV that contain multiple genetic mutations compared to wild-type (WT) RhCMV. In many studies, animals have been inoculated by nonnatural routes (e.g., subcutaneous, intravenous) that do not recapitulate disease progression via the normative route of mucosal exposure. Accordingly, the natural history of RhCMV would be more accurately reproduced by infecting macaques with strains of RhCMV that reflect the WT genome using natural routes of mucosal transmission. Here, we tested two WT-like RhCMV strains, UCD52 and UCD59, and demonstrated that systemic infection and frequent, high-titer viral shedding in bodily fluids occurred following oral inoculation. RhCMV disseminated to a broad range of tissues, including the central nervous system and reproductive organs. Commonly infected tissues included the thymus, spleen, lymph nodes, kidneys, bladder, and salivary glands. Histological examination revealed prominent nodular hyperplasia in spleens and variable levels of lymphoid lymphofollicular hyperplasia in lymph nodes. One of six inoculated animals had limited viral dissemination and shedding, with commensurately weak antibody responses to RhCMV antigens. These data suggest that long-term RhCMV infection parameters might be restricted by local innate factors and/or de novo host immune responses in a minority of primary infections. Together, we have established an oral RhCMV infection model that mimics natural HCMV infection. The virological and immunological parameters characterized in this study will greatly inform HCMV vaccine designs for human immunization. IMPORTANCE Human cytomegalovirus (HCMV) is globally ubiquitous with high seroprevalence rates in all communities. HCMV infections can occur vertically following mother-to-fetus transmission across the placenta and horizontally following shedding of virus in bodily fluids in HCMV-infected hosts and subsequent exposure of susceptible individuals to virus-laden fluids. Intrauterine HCMV has long been recognized as an infectious threat to fetal growth and development. Since vertical HCMV infections occur following horizontal HCMV transmission to the pregnant mother, the nonhuman primate model of HCMV pathogenesis was used to characterize the virological and immunological parameters of infection following primary mucosal exposures to rhesus cytomegalovirus.

A Systematic Review of the Development and Validation of the Heat Vulnerability Index: Major Factors, Methods, and Spatial Units.

PURPOSE OF REVIEW: This review aims to identify the key factors, methods, and spatial units used in the development and validation of the heat vulnerability index (HVI) and discuss the underlying limitations of the data and methods by evaluating the performance of the HVI. RECENT FINDINGS: Thirteen studies characterizing the factors of the HVI development and relating the index with validation data were identified. Five types of factors (i.e., hazard exposure, demographic characteristics, socioeconomic conditions, built environment, and underlying health) of the HVI development were identified, and the top five were social cohesion, race, and/or ethnicity, landscape, age, and economic status. The principal component analysis/factor analysis (PCA/FA) was often used in index development, and four types of spatial units (i.e., census tracts, administrative area, postal code, grid) were used for establishing the relationship between factors and the HVI. Moreover, although most studies showed that a higher HVI was often associated with the increase in health risk, the strength of the relationship was weak. SUMMARY: This review provides a retrospect of the major factors, methods, and spatial units used in development and validation of the HVI and helps to define the framework for future studies. In the future, more information on the hazard exposure, underlying health, governance, and protection awareness should be considered in the HVI development, and the duration and location of validation data should be strengthened to verify the reliability of HVI. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40641-021-00173-3.

Comparative analyses on epidemiological characteristics of dengue fever in Guangdong and Yunnan, China, 2004-2018.

BACKGROUND: In China, Guangdong and Yunnan are the two most dengue-affected provinces. This study aimed to compare the epidemiological characteristics of dengue fever in Guangdong and Yunnan during 2004-2018. METHODS: Descriptive analyses were used to explore the temporal, spatial, and demographic distribution of dengue fever. RESULTS: Of the 73,761 dengue cases reported in mainland China during 2004-2018, 93.7% indigenous and 65.9% imported cases occurred in Guangdong and Yunnan, respectively. A total of 55,970 and 5938 indigenous cases occurred in 108 Guangdong and 8 Yunnan counties, respectively during 2004-2018. Whereas 1146 and 3050 imported cases occurred in 84 Guangdong and 72 Yunnan counties, respectively during 2004-2018. Guangdong had a much higher average yearly indigenous incidence rate (3.65 (1/100000) vs 0.86 (1/100000)), but a much lower average yearly imported incidence rate (0.07 (1/100000) vs 0.44(1/100000)) compared with Yunnan in 2004-2018. Furthermore, dengue fever occurred more widely in space and more frequently in time in Guangdong. Guangdong and Yunnan had similar seasonal characteristics for dengue fever, but Guangdong had a longer peak period. Most dengue cases were clustered in the south-western border of Yunnan and the Pearl River Delta region in Guangdong. Most of the imported cases (93.9%) in Guangdong and Yunnan were from 9 Southeast Asian countries. Thailand, Cambodia, and Malaysia imported mainly into Guangdong while Myanmar and Laos imported into Yunnan. There was a strong male predominance among imported cases and an almost equal gender distribution among indigenous cases. Most dengue cases occurred in individuals aged 21-50 years, accounting for 57.3% (Guangdong) vs. 62.8% (Yunnan) of indigenous and 83.2% (Guangdong) vs. 62.6% (Yunnan) of imported cases. The associated major occupations (house worker or unemployed, retiree, and businessman, for indigenous cases; and businessman, for imported cases), were similar. However, farmers accounted for a larger proportion of dengue cases in Yunnan. CONCLUSIONS: Identifying the different epidemiological characteristics of dengue fever in Guangdong and Yunnan can be helpful to formulate targeted, strategic plans, and implement effective public health prevention measures in China.

Entomological and Molecular Surveillance of Anopheles Mosquitoes in Freetown, Sierra Leone, 2019.

Background: Malaria is endemic in Sierra Leone, with stable and perennial transmission in all parts of the country. At present, the main prevention and control measures for mosquito vectors here involve insecticide treated nets (ITN) and indoor residual spraying (IRS). The most recent entomological surveillance was conducted prior to the civil war, between 1990 and 1994. Therefore, a new entomological surveillance required to support targeted malaria control strategies. Methods:Anopheles mosquitoes were collected between June and December 2019 using the light trap method. On these, we conducted species identification, analyzed seasonal fluctuation and Plasmodium infection rate, and monitored insecticide resistance. Results: Surveillance of seasonal fluctuation showed that there were two peak of Anopheles density in July (mean 13.67 mosquitoes/trap/night) and October (mean 13.00 mosquitoes/trap/night). Meanwhile, the lowest Anopheles density was seen in early September. Ninety-one representatives of Anopheles gambiae s.l. were selected and identified as An. coluzzii (n = 35) and An. gambiae s.s. (n = 56) using PCR. An. coluzzii and An. gambiae s.s. were found to be heterozygous resistant to the knockdown resistance (kdr) L1014F mutation (100%). Meanwhile, the East African mutation (kdr L1014S) was absent in the tested mosquitoes. Three mosquitoes that tested positive for the parasite, had an individual Plasmodium falciparum infection rate of 12.50, 16.67, and 14.29%. The sampling dates of positive mosquitoes were distributed in the two periods of peak Anopheles mosquito density. Conclusion: This study identified the dominant Anopheles species in Freetown as An. gambiae while the predominant species within the An. gambiae complex was An. gambiae sensu stricto. Surveillance of seasonal fluctuations and high P. falciparum infection rates in Anopheles indicate that the alternation of drought and rainy seasons from June to July, and from October to November, are the key periods for malaria control and prevention in Freetown, Sierra Leone. The high frequency of kdr allele mutations in An. gambiae calls for close monitoring of vector susceptibility to insecticides and tracing of resistance mechanisms in order to develop more effective vector control measures and strategies.

Spatial Dynamics of Dengue Fever in Mainland China, 2019.

New spatial characteristics of dengue fever in mainland China during 2019 were analyzed. There was a dengue fever outbreak in mainland China in 2019, with 15,187 indigenous cases in 13 provinces, 1281 domestic imported cases from 12 provinces and 5778 overseas imported cases from 47 countries, more than the previous cases during the period 2005-2018, except for in 2014. Indigenous cases occurred in Sichuan, Hubei and Chongqing in 2019. There have been big changes in the spatial distribution and proportion of dengue cases. Indigenous cases were not only located in the southwestern border and southeastern coastal provinces of Yunnan, Guangdong, Guangxi and Fujian but also in the central provinces of Jiangxi and Chongqing. Domestic imported cases were not only from Guangdong, but also from Yunnan. There were five new sources of importation of cases. Overseas imported cases were mainly from Cambodia and Myanmar in 2019. Understanding the new spatial characteristics of dengue fever in China helps to formulate targeted, strategic plans and implement effective public health prevention and control measures.

In vitro and in vivo characterization of a recombinant rhesus cytomegalovirus containing a complete genome.

Cytomegaloviruses (CMVs) are highly adapted to their host species resulting in strict species specificity. Hence, in vivo examination of all aspects of CMV biology employs animal models using host-specific CMVs. Infection of rhesus macaques (RM) with rhesus CMV (RhCMV) has been established as a representative model for infection of humans with HCMV due to the close evolutionary relationships of both host and virus. However, the only available RhCMV clone that permits genetic modifications is based on the 68-1 strain which has been passaged in fibroblasts for decades resulting in multiple genomic changes due to tissue culture adaptations. As a result, 68-1 displays reduced viremia in RhCMV-naïve animals and limited shedding compared to non-clonal, low passage isolates. To overcome this limitation, we used sequence information from primary RhCMV isolates to construct a full-length (FL) RhCMV by repairing all mutations affecting open reading frames (ORFs) in the 68-1 bacterial artificial chromosome (BAC). Inoculation of adult, immunocompetent, RhCMV-naïve RM with the reconstituted virus resulted in significant viremia in the blood similar to primary isolates of RhCMV and furthermore led to high viral genome copy numbers in many tissues at day 14 post infection. In contrast, viral dissemination was greatly reduced upon deletion of genes also lacking in 68-1. Transcriptome analysis of infected tissues further revealed that chemokine-like genes deleted in 68-1 are among the most highly expressed viral transcripts both in vitro and in vivo consistent with an important immunomodulatory function of the respective proteins. We conclude that FL-RhCMV displays in vitro and in vivo characteristics of a wildtype virus while being amenable to genetic modifications through BAC recombineering techniques.

Spatiotemporal dynamics of hemorrhagic fever with renal syndrome in Jiangxi province, China.

Historically, Jiangxi province has had the largest HFRS burden in China. However, thus far, the comprehensive understanding of the spatiotemporal distributions of HFRS is limited in Jiangxi. In this study, seasonal decomposition analysis, spatial autocorrelation analysis, and space-time scan statistic analyses were performed to detect the spatiotemporal dynamics distribution of HFRS cases from 2005 to 2018 in Jiangxi at the county scale. The epidemic of HFRS showed the characteristic of bi-peak seasonality, the primary peak in winter (November to January) and the second peak in early summer (May to June), and the amplitude and the magnitude of HFRS outbreaks have been increasing. The results of global and local spatial autocorrelation analysis showed that the HFRS epidemic exhibited the characteristic of highly spatially heterogeneous, and Anyi, Fengxin, Yifeng, Shanggao, Jing'an and Gao'an county were hot spots areas. A most likely cluster, and two secondary likely clusters were detected in 14-years duration. The higher risk areas of the HFRS outbreak were mainly located in Jiangxi northern hilly state, spreading to Wuyi mountain hilly state as time advanced. This study provided valuable information for local public health authorities to design and implement effective measures for the control and prevention of HFRS.

Climate factors driven typhus group rickettsiosis incidence dynamics in Xishuangbanna Dai autonomous prefecture of Yunnan province in China, 2005-2017.

BACKGROUND: Typhus group rickettsiosis (TGR), which is a neglected vector-borne infectious disease, including epidemic typhus and endemic typhus. We explored the lag effects and nonlinear association between meteorological factors and TGR incidence in Xishuangbanna Dai autonomous prefecture from 2005 to 2017, China. METHODS: A Poisson regression with a distributed lag nonlinear model (DLNM) was utilized to analyze TGR cases data and the contemporaneous meteorological data. RESULTS: A J-shaped nonlinear association between weekly mean temperature and TGR incidence was found. The cumulative exposure to weekly mean temperature indicated that the RR increased with the increment of temperature. Taking the median value as the reference, lower temperatures could decrease the risk of TGR incidence, while higher temperatures could increase the risk of TGR incidence and last for 21 weeks. We also found a reversed U-shaped nonlinear association between weekly mean precipitation and TGR incidence. Precipitation between 5 mm and 13 mm could increase the risk of TGR incidence. Taking the median value as the reference, no precipitation and lower precipitation could decrease the risk of TGR incidence, while higher precipitation could increase the risk of TGR incidence and last for 18 weeks. CONCLUSIONS: The prevention and control measures of TGR should be implemented according to climatic conditions by the local government and health departments in order to improve the efficiency.

Cytomegalovirus-vectored vaccines for HIV and other pathogens.

: The use of cytomegalovirus (CMV) as a vaccine vector to express antigens against multiple infectious diseases, including simian immunodeficiency virus, Ebola virus, plasmodium, and mycobacterium tuberculosis, in rhesus macaques has generated extraordinary levels of protective immunity against subsequent pathogenic challenge. Moreover, the mechanisms of immune protection have altered paradigms about viral vector-mediated immunity against ectopically expressed vaccine antigens. Further optimization of CMV-vectored vaccines, particularly as this approach moves to human clinical trials will be augmented by a more complete understanding of how CMV engenders mechanisms of immune protection. This review summarizes the particulars of the specific CMV vaccine vector that has been used to date (rhesus CMV strain 68-1) in relation to CMV natural history.

Epidemiological characteristics and spatiotemporal patterns of typhus group rickettsiosis at the county level in China, 2005-2017.

OBJECTIVE: To explore the epidemiological characteristics and spatiotemporal patterns of typhus group rickettsiosis (TGR) in mainland China. METHODS: A chi-squared test was used to compare the differences in the age and occupation distributions across the different years. Time-series analyses, spatial clustering analyses, and spatiotemporal scan statistics were used to detect the spatiotemporal patterns of the TGR incidence. RESULTS: A total of 29,211 TGR cases were collected. Of these cases, 63.1% occurred from May to October, and 88.4% occurred in individuals between 0 and 59 years old. There was a significant spatial TGR heterogeneity from 2005 to 2017. The hotspots were located mainly in the southwestern, southern, and circum-Bohai Sea regions of northern China. Eighteen spatiotemporal clusters were observed using Kulldorff's space-time scan statistic, and the primary cluster included three counties, Jinghong city, Menghai county, and Mengla county. CONCLUSIONS: TGR is widely distributed in China, and it is a serious threat to public health. The hotspots were located mainly in the southwestern, southern, and circum-Bohai Sea regions of northern China, and the primary spatiotemporal cluster showed a trend shifting from circum-Bohai Sea regions to the southwestern regions. Targeted interventions should be executed in high-risk regions for precise prevention and control.

Determination of Factors Affecting Dengue Occurrence in Representative Areas of China: A Principal Component Regression Analysis.

Background: Determination of the key factors affecting dengue occurrence is of significant importance for the successful response to its outbreak. Yunnan and Guangdong Provinces in China are hotspots of dengue outbreak during recent years. However, few studies focused on the drive of multi-dimensional factors on dengue occurrence failing to consider the possible multicollinearity of the studied factors, which may bias the results. Methods: In this study, multiple linear regression analysis was utilized to explore the effect of multicollinearity among dengue occurrences and related natural and social factors. A principal component regression (PCR) analysis was utilized to determine the key dengue-driven factors in Guangzhou city of Guangdong Province and Xishuangbanna prefecture of Yunnan Province, respectively. Results: The effect of multicollinearity existed in both Guangzhou city and Xishuangbanna prefecture, respectively. PCR model revealed that the top three contributing factors to dengue occurrence in Guangzhou were Breteau Index (BI) (positive correlation), the number of imported dengue cases lagged by 1 month (positive correlation), and monthly average of maximum temperature lagged by 1 month (negative correlation). In contrast, the top three factors contributing to dengue occurrence in Xishuangbanna included monthly average of minimum temperature lagged by 1 month (positive correlation), monthly average of maximum temperature (positive correlation), monthly average of relative humidity (positive correlation), respectively. Conclusion: Meteorological factors presented stronger impacts on dengue occurrence in Xishuangbanna, Yunnan, while BI and the number of imported cases lagged by 1 month played important roles on dengue transmission in Guangzhou, Guangdong. Our findings could help to facilitate the formulation of tailored dengue response mechanism in representative areas of China in the future.

Spatio-temporal patterns of scrub typhus in mainland China, 2006-2017.

BACKGROUND: Scrub typhus, a serious public health problem in the Asia-Pacific area, is endemic in the "tsutsugamushi triangle" area. Scrub typhus has been widespread and has become a significant health concern in China. However, spatiotemporal patterns need to be investigated further. OBJECTIVE: This study aims to explore spatiotemporal patterns, diffusion characteristics and regional distribution differences of scrub typhus cases in mainland China from January 2006 to December 2017. METHOD: Monthly cases of scrub typhus reported at the county level during 2006-2017 were obtained. Time-series analyses, spatial distribution analyses, spatial diffusion analyses, spatial autocorrelation analyses and space-time scan statistic analyses were used to explore spatiotemporal characteristics of scrub typhus. RESULTS: A total of 121 251 scrub typhus cases were reported in 30 provinces (or municipalities) of mainland China during 2006-2017, which rose exponentially. There were seasonal characteristics from June to November for scrub typhus. Scrub typhus had been diffused from south, southwest, southeast and eastern coasts to center, north, northeast and northwest in mainland China. Scrub typhus occurrences were from point to surrounding regions, and from south to north every year. The peak periods of scrub typhus became longer and longer from north to southwest to south in mainland China. There existed a single peak in Southwest region and North region, respectively, but existed a bimodal peak for South region. Scrub typhus cases were clustered in Yunnan, Guangdong, Guangxi, Fujian and Anhui among June to November. The scrub typhus epidemics in Guangdong and Yunnan were the most serious. CONCLUSIONS: The results in this study can be guide targeted public health interventions against scrub typhus at the county level.

Exploring Epidemiological Characteristics of Domestic Imported Dengue Fever in Mainland China, 2014-2018.

Epidemiological characteristics of domestic imported dengue fever in mainland China, 2014-2018, including time-series, spatial mobility and crowd features, were analyzed. There existed seasonal characteristics from August to November. The 872 domestic imported cases from 8 provinces, located in the southeastern, southwestern and southern coastal or border areas, were imported to 267 counties in 20 provinces of mainland China, located in the outer areas along the southwest-northeast line. The 628 domestic imported cases were still imported to the adjacent counties in the provinces themselves, 234 domestic imported cases were imported to 12 other provinces except the 8 original exported provinces, 493 cases in 2014 reached the peak, and 816 domestic imported cases were from Guangdong (675) and Yunnan (141). Domestic imported cases from Guangdong were imported to 218 counties, and 475 cases from Guangdong were imported to the adjacent counties in Guangdong itself. There were more male cases than female cases except in 2016. Domestic imported cases were clustered from 21 to 50 years old. The top three cases were from farmer, worker and housework or unemployed. The findings are helpful to formulate targeted, strategic plans and implement effective public health prevention and control measures.