COVID-19 prevention measures reduce dengue spread in Yunnan Province, China, but do not reduce established outbreak.
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ABSTRACT: ABSTRACTThe COVID-19 pandemic and measures against it provided a unique opportunity to understand the transmission of other infectious diseases and to evaluate the efficacy of COVID-19 prevention measures on them. Here we show a dengue epidemic in Yunnan, China, during the pandemic of COVID-19 was dramatically reduced compared to non-pandemic years and, importantly, spread was confined to only one city, Ruili. Three key features characterized this dengue outbreak: (i) the urban-to-suburban spread was efficiently blocked; (ii) the scale of epidemic in urban region was less affected; (iii) co-circulation of multiple strains was attenuated. These results suggested that countermeasures taken during COVID-19 pandemic are efficient to prevent dengue transmission between cities and from urban to suburban, as well to reduce the co-circulation of multiple serotypes or genotypes. Nevertheless, as revealed by the spatial analysis, once the dengue outbreak was established, its distribution was very stable and resistant to measures against COVID-19, implying the possibility to develop a precise prediction method.
Project description:Yunnan Province, China is thought to be the original source of biovar Orientalis of Yersinia pestis, the causative agent of the third plague pandemic that has spread globally since the end of the 19th century. Although encompassing a large area of natural plague foci, Y. pestis strains have rarely been found in live rodents during surveillance in Yunnan, and most isolates are from rodent corpses and their fleas. In 2017, 10 Y. pestis strains were isolated from seven live rodents and three fleas in Heqing County (HQ) of Yunnan. These strains were supposed to have low virulence to local rodents Eothenomys miletus and Apodemus chevrieri because the rodents were healthy and no dead animals were found in surrounding areas, as had occurred in previous epizootic disease. We performed microscopic and biochemical examinations of the isolates,and compared their whole-genome sequences and transcriptome with those of 10 high virulence Y. pestis strains that were isolated from the adjacent city (Lijiang). We analyzed the phenotypic, genomic, and transcriptomic characteristics of live rodent isolates. The isolates formed a previously undefined monophyletic branch of Y. pestis that was named 1.IN5. Six SNPs, two indels, and one copy number variation were detected between live rodent isolates and the high virulence neighbors. No obvious functional consequence of these variations was found according to the known annotation information. Among the genes that were differentially expressed between the live rodent isolates and their high virulence neighbors, we detected five iron transfer-related genes that were significantly up-regulated in live rodent isolates compared with high virulence isolates (|log2 (FC) | >1, p.adjust <0.05), indicating these genes may be related to the low-virulence phenotype. The novel genotype of Y. pestis reported here provides further insights into the evolution and spread of plague as well as clues that may help to decipher the virulence mechanism of this notorious pathogen.
Project description:In August 2013, Xishuangbanna, Yunnan Province, China, had its first dengue outbreak. Dengue virus (DENV) RNA detection in sera or viral isolates revealed that all 222 autochthonous patients detected and three Chinese travelers from Laos (imported cases) were positive for DENV-3 serotype, while DENV-1 and DENV-4 were detected in travelers from Myanmar and Thailand during the outbreak. For 33 suspected dengue cases collected before the outbreak, two imported cases from Laos and nine residents living in Laos (Laotian cases) were positive for DENV-3. Further, a random subset of 33 positive cases for DENV-3 was sequenced for the full envelope gene of DENV. Phylogenetic analysis showed that all of the 25 autochthonous cases sequenced were grouped into the same clade, genotype II of DENV-3, with imported cases from Laos and Laotian cases. These results suggest that the genotype II of DENV-3 was associated with the outbreak and may have originated from the virus circulating in Laos.
Project description:In 2015, a dengue outbreak with 1,067 reported cases occurred in Xishuangbanna, a city in China that borders Burma and Laos. To characterize the virus, the complete genome sequence was obtained and phylogenetic, mutation, substitution and recombinant analyses were performed. DENV-NS1 positive serum samples were collected from dengue fever patients, and complete genome sequences were obtained through RT-qPCR from these serum samples. Phylogenetic trees were then constructed by maximum likelihood phylogeny test (MEGA7.0), followed by analysis of nucleotide mutation and amino acid substitution. The recombination events among DENVs were also analyzed by RDP4 package. The diversity analysis of secondary structure for translated viral proteins was also performed. The complete genome sequences of four amplified viruses (YNXJ10, YNXJ12, YNXJ13, and YNXJ16) were 10,742, 10,742, 10,741, and 10,734 nucleotides in length, and phylogenetic analysis classified the viruses as cosmopolitan genotype of DENV-2. All viruses were close to DENV Singapore 2013 (KX380828.1) and the DENV China 2013 (KF479233.1). In comparison to DENV-2SS (M29095), the total numbers of base substitutions were 712 nt (YNXJ10), 809 nt (YNXJ12), 772 nt (YNXJ13), and 841 nt (YNXJ16), resulting in 109, 171, 130, and 180 amino acid substitutions in translated regions, respectively. In addition, compared with KX380828.1, there were 44, 105, 64, and 116 amino acid substitutions in translated regions, respectively. The highest mutation rate occurred in the prM region, and the lowest mutation rate occurred in the NS4B region. Most of the recombination events occurred in the prM, E and NS2B/3 regions, which corresponded with the mutation frequency of the related portion. Secondary structure prediction within the 3,391 amino acids of DENV structural proteins showed there were 7 new possible nucleotide-binding sites and 6 lost sites compared to DENV-2SS. In addition, 41 distinct amino acid changes were found in the helix regions, although the distribution of the exposed and buried regions changed only slightly. Our findings may help to understand the intrinsic geographical relatedness of DENV-2 and contributes to the understanding of viral evolution and its impact on the epidemic potential and pathogenicity of DENV.
Project description:Dengue fever is a severe public heath challenge in south China. A dengue outbreak was reported in Chaozhou city, China in 2015. Intensified interventions were implemented by the government to control the epidemic. However, it is still unknown the degree to which intensified control measures reduced the size of the epidemics, and when should such measures be initiated to reduce the risk of large dengue outbreaks developing?We selected Xiangqiao district as study setting because the majority of the indigenous cases (90.6%) in Chaozhou city were from this district. The numbers of daily indigenous dengue cases in 2015 were collected through the national infectious diseases and vectors surveillance system, and daily Breteau Index (BI) data were reported by local public health department. We used a compartmental dynamic SEIR (Susceptible, Exposed, Infected and Removed) model to assess the effectiveness of control interventions, and evaluate the control effect of intervention timing on dengue epidemic.A total of 1250 indigenous dengue cases was reported from Xiangqiao district. The results of SEIR modeling using BI as an indicator of actual control interventions showed a total of 1255 dengue cases, which is close to the reported number (n = 1250). The size and duration of the outbreak were highly sensitive to the intensity and timing of interventions. The more rigorous and earlier the control interventions implemented, the more effective it yielded. Even if the interventions were initiated several weeks after the onset of the dengue outbreak, the interventions were shown to greatly impact the prevalence and duration of dengue outbreak.This study suggests that early implementation of rigorous dengue interventions can effectively reduce the epidemic size and shorten the epidemic duration.
Project description:A total of 1067 serum samples were collected from febrile patients in Xishuangbanna, Yunnan, 2015. Of these, 852 cases were confirmed to be dengue NS1-positive. 76 structural protein genes were sequenced through RT-PCR based on the viral RNAs extracted from serum samples. Phylogenetic analysis revealed that all strains were classified as cosmopolitan genotype of DENV-2. After comparing with the DENV-2SS, 173 base substitutions were found in 76 sequences, resulting in 43 nonsynonymous mutations, of which 22 mutations existed among all samples. According to secondary structure prediction, 8 new possible nucelotide/protein binding sites were found and another 4 sites were lost among the 775 amino acids of DENV structural proteins as compared with DENV-2SS. Meanwhile, 6 distinct amino acid changes were found in the helix and strand regions, and the distribution of the exposed and buried regions was slightly altered. The results indicated that the epidemic dengue strains of Xishuangbanna in 2015 are most similar to the Indian strain in 2001 and the Sri Lankan strain in 2004. Moreover, it also show a very strong similarity to the epidemic strains of Fujian province in 1999 and 2010, which show that there is an internal recycling epidemic trend of DENV in China.
Project description:Rabies is an important but underestimated threat to public health, with most cases reported in Asia. Since 2000, a new epidemic wave of rabies has emerged in Yunnan Province, southwestern China, which borders three countries in Southeast Asia.We estimated gene-specific evolutionary rates for rabies virus using available data in GenBank, then used this information to calibrate the timescale of rabies virus (RABV) spread in Asia. We used 452 publicly available geo-referenced complete nucleoprotein (N) gene sequences, including 52 RABV sequences that were recently generated from samples collected in Yunnan between 2008 and 2012.The RABV N gene evolutionary rate was estimated to be 1.88?×?10-4 (1.37-2.41?×?10-4, 95% Bayesian credible interval, BCI) substitutions per site per year. Phylogenetic reconstructions show that the currently circulating RABV lineages in Yunnan result from at least seven independent introductions (95% BCI: 6-9 introductions) and represent each of the three main Asian RABV lineages, SEA-1, -2 and -3. We find that Yunnan is a sink location for the domestic spread of RABV and connects RABV epidemics in North China, South China, and Southeast Asia. Cross-border spread from southeast Asia (SEA) into South China, and intermixing of the North and South China epidemics is also well supported. The influx of RABV into Yunnan from SEA was not well-supported, likely due to the poor sampling of SEA RABV diversity. We found evidence for a lineage displacement of the Yunnan SEA-2 and -3 lineages by Yunnan SEA-1 strains, and considered whether this could be attributed to fitness differences.Overall, our study contributes to a better understanding of the spread of RABV that could facilitate future rabies virus control and prevention efforts.
Project description:BackgroundOutbreaks of dengue fever are often found among Dai ethnical communities along China-Myanmar border. The objective of this study was: 1) to investigate residents' health perceptions, knowledge and control willingness to participate in dengue control and 2) to identify factors associated with control willingness among the Dai ethnic community.MethodsThis is a mixed method study of a cross-sectional design, in which qualitative in-depth interviews and quantitative household questionnaire surveys are included.ResultsQuestionnaire was administered to 261 household heads, and in-depth interview was conducted with 18 key informants. Of them, many participants (70%, 182/259) and 12 key informants (66.7%) from the two rural communities believed that the Lord Buddha would protect the good people. Majority of the participants (81.4%, 206/253) knew that fever was one of dengue fever symptoms and most of them (82.2%, 213/259) indicated that mosquitoes could transmit dengue fever. However, only one third of the participants (30.1%, 78/259) indicated the perceived susceptibility of dengue fever, and only a half of them (50.2%, 130/259) indicated the perceived severity of dengue fever. Multivariate logistic analysis (MLA) indicated that the participants with family wealth index (FWI) 4-5 (OR: 22.9728; 95%CI: 2.4257-217.5688, p = 0.0063) were more likely to turn containers upside down (TCUD) compared to those with FWI 1-3; and the participants in the urban community (OR: 0.0239; 95%CI: 0.0019-0.3032, p = 0.004) were less likely to TCUD compared to those in the two rural communities. Around one third of the participants (36.8%, 96/239) reported that they were willing to seek treatment first for dengue fever from public health facilities. The MLA identified that the participants with the perceived severity of dengue fever (OR: 5.0564; 95%CI: 2.0672-12.3683, p = 0.0004), and with beliefs of sound hygiene helpful to people's health (OR: 11.5671; 95%CI: 2.0505-65.2502, p = 0.0055) were more likely to seek treatment first for dengue fever from the public health facilities.ConclusionThe study finds that most of Dai people have sound knowledge. However, health educational interventions should target to promote the perceived susceptibility and the perceived severity of dengue fever among Dai people.
Project description:BackgroundThe paradigm shift in hepatitis C virus (HCV) treatment options in the last five years has raised the prospect of eliminating the disease as a global health threat. This will require a step-change in the number being treated with the new direct-acting antivirals (DAAs). Given constrained budgets and competing priorities, policy makers need information on how to scale-up access to HCV treatment. To inform such decisions, we examined the cost effectiveness of screening and treatment interventions in Yunnan, China.Methods and findingsWe simulated the HCV epidemic using a previously published model of HCV transmission and disease progression, calibrated to Yunnan data, and implemented a range of treatment and screening interventions from 2019. We incorporated treatment, diagnosis, and medical costs (expressed in 2019 US Dollars, USD) to estimate the lifetime benefits and costs of interventions. Using this model, we asked: is introducing DAAs cost effective from a healthcare sector perspective; what is the optimal combination of screening interventions; and what is the societal return on investment of intervention? The incremental cost-effectiveness ratio (ICER) of switching to DAAs with a median cost of 7,400 USD (50,000 Chinese Yuan) per course is 500 USD/disability adjusted life year (DALY) averted; at a threshold of 50% of Yunnan gross domestic product (2,600 USD), switching to DAAs is cost effective 94% of the time. At this threshold, the optimal, cost-effective intervention comprises screening people who inject drugs, those in HIV care, men who have sex with men, and ensuring access to DAAs for all those newly diagnosed with HCV. For each USD invested in this intervention, there is an additional 0·80 USD (95% credible interval: 0·17-1·91) returned through reduced costs of disease or increased productivity. Returns on investment are lower (and potentially negative) if a sufficiently long-term horizon, encompassing the full stream of future benefits, is not adopted. The study had two key limitations: costing data were not always specific to Yunnan province but were taken from China-level studies; and modelled interventions may require more operational research to ensure they can be effectively and efficiently rolled-out to the entire province.ConclusionsIntroducing DAAs is cost effective, the optimal package of screening measures is focussed on higher risk groups, and there are likely to be positive returns from investing in such HCV interventions. Our analysis shows that targeted investment in HCV interventions will have net benefits to society; these benefits will only increase as DAA costs fall.
Project description:Poverty and malaria appear to have an intertwined link. This paper aims to define the relationship between poverty and malaria in Yunnan, China, and to make recommendations for future research in this important area. Data on malaria prevalence and the population's income in each county between 2005 and 2010 were obtained from the Yunnan Center for Disease Control and Prevention and the Yunnan Bureau of Statistics, respectively. Geographic mapping shows an apparent spatial convergence of poverty and the incidence of malaria at a county level, and suggests that poverty may be one of the drivers of malaria transmission in Yunnan. Future research should focus on: 1. measuring and quantifying the relationship between poverty and the malaria burden at the individual, community, county and regional level in Yunnan; and 2. developing the GIS-based spatial decision support system (SDSS) framework in malaria endemic areas, particularly along the border areas in Yunnan.
Project description:To limit the spread of severe acute respiratory syndrome coronavirus 2, the government of China has been monitoring infected travelers and minimizing cold-chain contamination. However, other factors might contribute to recurring outbreaks. We analyze the role of undocumented migrants as potential transmitters of severe acute respiratory syndrome coronavirus 2 in China.