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Heliyon May 2024In recent years, research on exosomal miRNAs has provided new insights into exploring the mechanism of viral infection and disease prevention. This study aimed to...
BACKGROUND
In recent years, research on exosomal miRNAs has provided new insights into exploring the mechanism of viral infection and disease prevention. This study aimed to investigate the serum exosomal miRNA expression profile of dengue-infected individuals through a community survey of dengue virus (DENV) infection.
METHODS
A seroprevalence study of 1253 healthy persons was first conducted to ascertain the DENV infection status in Baiyun District, Guangzhou. A total of 18 serum samples, including 6 healthy controls (HC), 6 asymptomatic DENV infections (AsymptDI), and 6 confirmed dengue fever patients (AcuteDI), were collected for exosome isolation and then sRNA sequencing. Through bioinformatics analysis, we discovered distinct serum exosomal miRNA profiles among the different groups and identified differentially expressed miRNAs (DEMs). These findings were further validated by qRT-PCR.
RESULTS
The community survey of DENV infection indicated that the DENV IgG antibody positivity rate among the population was 11.97 % in the study area, with asymptomatic infected individuals accounting for 93.06 % of the anti-DENV IgG positives. The age and Guangzhou household registration were associated with DENV IgG antibody positivity by logistic regression analysis. Distinct miRNA profiles were observed between healthy individuals and DENV infections. A total of 1854 miRNAs were identified in 18 serum exosome samples from the initial analysis of the sequencing data. Comparative analysis revealed 23 DEMs comprising 5 upregulated and 18 downregulated miRNAs in the DENV-infected group (mergedDI). In comparison to AcuteDI, 18 upregulated miRNAs were identified in AsymptDI. Moreover, functional enrichment of the predicted target genes of DEMs indicated that these miRNAs were involved in biological processes and pathways related to cell adhesion, focal adhesion, endocytosis, and ECM-receptor interaction. Eight DEMs were validated by qRT-PCR.
CONCLUSION
The Baiyun District of Guangzhou exhibits a notable proportion of asymptomatic DENV infections as suggested in other research, highlighting the need for enhanced monitoring and screening of asymptomatic persons and the elderly. Differential miRNA expression among healthy, symptomatic and asymptomatic DENV-infected individuals suggests their potential as biomarkers for distinguishing DENV infection and offers new avenues of investigating the mechanisms underlying DENV asymptomatic infections.
PubMed: 38807894
DOI: 10.1016/j.heliyon.2024.e31546 -
Scientific Reports May 2024The Ae. albopictus mosquito has gained global attention due to its ability to transmit viruses, including the dengue and zika. Mosquito control is the only effective way...
Resistance to pyrethroids and the relationship between adult resistance and knockdown resistance (kdr) mutations in Aedes albopictus in dengue surveillance areas of Guizhou Province, China.
The Ae. albopictus mosquito has gained global attention due to its ability to transmit viruses, including the dengue and zika. Mosquito control is the only effective way to manage dengue fever, as no effective treatments or vaccines are available. Insecticides are highly effective in controlling mosquito densities, which reduces the chances of virus transmission. However, Ae. albopictus has developed resistance to pyrethroids in several provinces in China. Pyrethroids target the voltage-gated sodium channel gene (VGSC), and mutations in this gene may result in knockdown resistance (kdr). Correlation studies between resistance and mutations can assist viruses in managing Ae. albopictus, which has not been studied in Guizhou province. Nine field populations of Ae. albopictus at the larval stage were collected from Guizhou Province in 2022 and reared to F1 to F2 generations. Resistance bioassays were conducted against permethrin, beta-cypermethrin, and deltamethrin for both larvae and adults of Ae. albopictus. Kdr mutations were characterized by PCR and sequencing. Additionally, the correlation between the kdr allele and pyrethroid resistance was analyzed. All nine populations of Ae. albopictus larvae and adults were found to be resistant to three pyrethroid insecticides. One kdr mutant allele at codon 1016, one at 1532 and three at 1534 were identified with frequencies of 13.86% (V1016G), 0.53% (I1532T), 58.02% (F1534S), 11.69% (F1534C), 0.06% (F1534L) and 0.99% (F1534P), respectively. Both V1016G and F1534S mutation mosquitoes were found in all populations. The kdr mutation F1534S was positively correlated with three pyrethroid resistance phenotypes (OR > 1, P < 0.05), V1016G with deltamethrin and beta-cypermethrin resistance (OR > 1, P < 0.05) and F1534C only with beta-cypermethrin resistance (OR > 1, P < 0.05). Current susceptibility status of wild populations of Ae. albopictus to insecticides and a higher frequency of kdr mutations from dengue-monitored areas in Guizhou Province are reported in this paper. Outcomes of this study can serve as data support for further research and development of effective insecticidal interventions against Ae. albopictus populations in Guizhou Province.
Topics: Animals; Pyrethrins; Aedes; Insecticide Resistance; China; Dengue; Mutation; Insecticides; Mosquito Vectors; Larva; Voltage-Gated Sodium Channels; Mosquito Control; Nitriles
PubMed: 38806622
DOI: 10.1038/s41598-024-63138-0 -
Nature Communications May 2024Understanding how emerging infectious diseases spread within and between countries is essential to contain future pandemics. Spread to new areas requires connectivity...
Understanding how emerging infectious diseases spread within and between countries is essential to contain future pandemics. Spread to new areas requires connectivity between one or more sources and a suitable local environment, but how these two factors interact at different stages of disease emergence remains largely unknown. Further, no analytical framework exists to examine their roles. Here we develop a dynamic modelling approach for infectious diseases that explicitly models both connectivity via human movement and environmental suitability interactions. We apply it to better understand recently observed (1995-2019) patterns as well as predict past unobserved (1983-2000) and future (2020-2039) spread of dengue in Mexico and Brazil. We find that these models can accurately reconstruct long-term spread pathways, determine historical origins, and identify specific routes of invasion. We find early dengue invasion is more heavily influenced by environmental factors, resulting in patchy non-contiguous spread, while short and long-distance connectivity becomes more important in later stages. Our results have immediate practical applications for forecasting and containing the spread of dengue and emergence of new serotypes. Given current and future trends in human mobility, climate, and zoonotic spillover, understanding the interplay between connectivity and environmental suitability will be increasingly necessary to contain emerging and re-emerging pathogens.
Topics: Dengue; Humans; Brazil; Mexico; Animals; Dengue Virus; Communicable Diseases, Emerging; Environment; Human Migration; Aedes
PubMed: 38806460
DOI: 10.1038/s41467-024-48465-0 -
Morbidity and Mortality Weekly Report.... May 2024Dengue is the most prevalent mosquitoborne viral illness worldwide and is endemic in Puerto Rico. Dengue's clinical spectrum can range from mild, undifferentiated...
PROBLEM/CONDITION
Dengue is the most prevalent mosquitoborne viral illness worldwide and is endemic in Puerto Rico. Dengue's clinical spectrum can range from mild, undifferentiated febrile illness to hemorrhagic manifestations, shock, multiorgan failure, and death in severe cases. The disease presentation is nonspecific; therefore, various other illnesses (e.g., arboviral and respiratory pathogens) can cause similar clinical symptoms. Enhanced surveillance is necessary to determine disease prevalence, to characterize the epidemiology of severe disease, and to evaluate diagnostic and treatment practices to improve patient outcomes. The Sentinel Enhanced Dengue Surveillance System (SEDSS) was established to monitor trends of dengue and dengue-like acute febrile illnesses (AFIs), characterize the clinical course of disease, and serve as an early warning system for viral infections with epidemic potential.
REPORTING PERIOD
May 2012-December 2022.
DESCRIPTION OF SYSTEM
SEDSS conducts enhanced surveillance for dengue and other relevant AFIs in Puerto Rico. This report includes aggregated data collected from May 2012 through December 2022. SEDSS was launched in May 2012 with patients with AFIs from five health care facilities enrolled. The facilities included two emergency departments in tertiary acute care hospitals in the San Juan-Caguas-Guaynabo metropolitan area and Ponce, two secondary acute care hospitals in Carolina and Guayama, and one outpatient acute care clinic in Ponce. Patients arriving at any SEDSS site were eligible for enrollment if they reported having fever within the past 7 days. During the Zika epidemic (June 2016-June 2018), patients were eligible for enrollment if they had either rash and conjunctivitis, rash and arthralgia, or fever. Eligibility was expanded in April 2020 to include reported cough or shortness of breath within the past 14 days. Blood, urine, nasopharyngeal, and oropharyngeal specimens were collected at enrollment from all participants who consented. Diagnostic testing for dengue virus (DENV) serotypes 1-4, chikungunya virus, Zika virus, influenza A and B viruses, SARS-CoV-2, and five other respiratory viruses was performed by the CDC laboratory in San Juan.
RESULTS
During May 2012-December 2022, a total of 43,608 participants with diagnosed AFI were enrolled in SEDSS; a majority of participants (45.0%) were from Ponce. During the surveillance period, there were 1,432 confirmed or probable cases of dengue, 2,293 confirmed or probable cases of chikungunya, and 1,918 confirmed or probable cases of Zika. The epidemic curves of the three arboviruses indicate dengue is endemic; outbreaks of chikungunya and Zika were sporadic, with case counts peaking in late 2014 and 2016, respectively. The majority of commonly identified respiratory pathogens were influenza A virus (3,756), SARS-CoV-2 (1,586), human adenovirus (1,550), respiratory syncytial virus (1,489), influenza B virus (1,430), and human parainfluenza virus type 1 or 3 (1,401). A total of 5,502 participants had confirmed or probable arbovirus infection, 11,922 had confirmed respiratory virus infection, and 26,503 had AFI without any of the arboviruses or respiratory viruses examined.
INTERPRETATION
Dengue is endemic in Puerto Rico; however, incidence rates varied widely during the reporting period, with the last notable outbreak occurring during 2012-2013. DENV-1 was the predominant virus during the surveillance period; sporadic cases of DENV-4 also were reported. Puerto Rico experienced large outbreaks of chikungunya that peaked in 2014 and of Zika that peaked in 2016; few cases of both viruses have been reported since. Influenza A and respiratory syncytial virus seasonality patterns are distinct, with respiratory syncytial virus incidence typically reaching its annual peak a few weeks before influenza A. The emergence of SARS-CoV-2 led to a reduction in the circulation of other acute respiratory viruses.
PUBLIC HEALTH ACTION
SEDSS is the only site-based enhanced surveillance system designed to gather information on AFI cases in Puerto Rico. This report illustrates that SEDSS can be adapted to detect dengue, Zika, chikungunya, COVID-19, and influenza outbreaks, along with other seasonal acute respiratory viruses, underscoring the importance of recognizing signs and symptoms of relevant diseases and understanding transmission dynamics among these viruses. This report also describes fluctuations in disease incidence, highlighting the value of active surveillance, testing for a panel of acute respiratory viruses, and the importance of flexible and responsive surveillance systems in addressing evolving public health challenges. Various vector control strategies and vaccines are being considered or implemented in Puerto Rico, and data from ongoing trials and SEDSS might be integrated to better understand epidemiologic factors underlying transmission and risk mitigation approaches. Data from SEDSS might guide sampling strategies and implementation of future trials to prevent arbovirus transmission, particularly during the expansion of SEDSS throughout the island to improve geographic representation.
Topics: Puerto Rico; Humans; Dengue; Sentinel Surveillance; Adult; Female; Adolescent; Middle Aged; Child; Male; Child, Preschool; Young Adult; Aged; Infant
PubMed: 38805389
DOI: 10.15585/mmwr.ss7303a1 -
Heliyon May 2024In endemic areas, the genetic diversity among co-circulating dengue virus (DENV) strains is considerable and new, highly divergent strains are identified on a regular...
In endemic areas, the genetic diversity among co-circulating dengue virus (DENV) strains is considerable and new, highly divergent strains are identified on a regular basis. It is thus critical to ensure that molecular diagnostic tools effectively detect virus genomes even in case of important genetic variation. Here, we tested both the pan-DENV detection capacity and the limit of detection of two real-time RT-PCR assays: (i) the commercial RealStar Altona 3.0 system and (ii) a laboratory developed test (LDT) combining two RT-PCR systems in a single reaction tube (DenAllDUO). We used a panel of DENV strains representative of the genetic diversity within DENV species, combined with three transcribed RNAs as surrogates for unavailable strains corresponding to recently discovered strains with substantial genetic divergence: DENV serotype 1 (DENV-1) Brun2014, DENV-2 QML22 and DENV-4 DKE121. Both systems (i) targeted the genome 3' untranslated region, (ii) displayed a broad detection spectrum, encompassing most of DENV species diversity, and (iii) detected the three aforementioned divergent strains. DenAllDUO detected all the strains tested, whereas the RealStar system failed to detect strains from DENV-4 genotype III. Altogether, our findings support the value of these two RT-PCR systems as part of the Dengue diagnostic arsenal.
PubMed: 38803933
DOI: 10.1016/j.heliyon.2024.e31252 -
The Brazilian Journal of Infectious... 2024The last five decades have seen a surge in viral outbreaks, particularly in tropical and subtropical regions like Brazil, where endemic arboviruses such as Dengue... (Review)
Review
BACKGROUND
The last five decades have seen a surge in viral outbreaks, particularly in tropical and subtropical regions like Brazil, where endemic arboviruses such as Dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV) pose significant threats. However, current diagnostic strategies exhibit limitations, leading to gaps in infection screening, arbovirus differential diagnoses, DENV serotyping, and life-long infection tracking. This deficiency impedes critical information availability regarding an individual's current infection and past infection history, disease risk assessment, vaccination needs, and policy formulation. Additionally, the availability of point-of-care diagnostics and knowledge regarding immune profiles at the time of infection are crucial considerations.
OBJECTIVES
This review underscores the urgent need to strengthen diagnostic methods for arboviruses in Brazil and emphasizes the importance of data collection to inform public health policies for improved diagnostics, surveillance, and policy formulation.
METHODS
We evaluated the diagnostic landscape for arboviral infections in Brazil, focusing on tailored, validated methods. We assessed diagnostic methods available for sensitivity and specificity metrics in the context of Brazil.
RESULTS
Our review identifies high-sensitivity, high-specificity diagnostic methods for arboviruses and co-infections. Grifols transcription-mediated amplification assays are recommended for DENV, CHIKV, and ZIKV screening, while IgG/IgM ELISA assays outperform Rapid Diagnostic Tests (RDTs). The Triplex real-time RT-PCR assay is recommended for molecular screening due to its sensitivity and specificity.
CONCLUSION
Enhanced diagnostic methods, on-going screening, and tracking are urgently needed in Brazil to capture the complex landscape of arboviral infections in the country. Recommendations include nationwide arbovirus differential diagnosis for DENV, ZIKV, and CHIKV, along with increased DENV serotyping, and lifelong infection tracking to combat enduring viral threats and reduce severe presentations.
Topics: Humans; Brazil; Arbovirus Infections; Arboviruses; Sensitivity and Specificity; Public Health; Data Collection; Dengue; Zika Virus Infection
PubMed: 38802065
DOI: 10.1016/j.bjid.2024.103766 -
Narra J Apr 2024Recent studies have demonstrated that cytokine dysregulation has a critical role in the pathogenesis of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS)....
Recent studies have demonstrated that cytokine dysregulation has a critical role in the pathogenesis of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The aim of this study was to investigate the association between tumor necrosis factor (TNF- α), interleukin 6 (IL-6), interleukin 10 (IL-10), and interleukin 17 (IL-17) with infection status, and severity of dengue. A prospective cross-sectional study was conducted at three hospitals in Gianyar regency and Denpasar municipality, Bali, Indonesia, from June to December 2022. Sixty-four dengue infected patients were involved. Patients' serum was tested for dengue infection using NS1 antigen rapid test, dengue virus immunoglobulin M (IgM) and immunoglobulin G (IgG) test, and reverse transcription polymerase chain reaction (RT-PCR). Cytokine levels (TNF-α, IL-6, IL-10, and IL-17) were measured using enzyme-linked immunosorbent assay (ELISA). Infection status was determined by combining serological and RT-PCR results, categorizing patients into primary and secondary infections. The present study found that DF patients had lower TNF-α, IL-6, and IL-17 but higher IL-10 levels compared to DHF patients (<0.001). Elevated TNF-α, IL-6, and IL-17 levels were higher in secondary infection, while IL-10 level was higher in primary infection (<0.001). In conclusion, cytokines play a crucial role in the interplay between cytokine dysregulation and dengue infection dynamics.
Topics: Humans; Indonesia; Severe Dengue; Male; Female; Cytokines; Cross-Sectional Studies; Prospective Studies; Adult; Dengue; Middle Aged; Interleukin-6; Enzyme-Linked Immunosorbent Assay; Adolescent; Interleukin-10; Tumor Necrosis Factor-alpha; Young Adult
PubMed: 38798833
DOI: 10.52225/narra.v4i1.309 -
MedRxiv : the Preprint Server For... May 2024Dengue virus (DENV) is currently causing epidemics of unprecedented scope in endemic settings and expanding to new geographical areas. It is therefore critical to track...
Dengue virus (DENV) is currently causing epidemics of unprecedented scope in endemic settings and expanding to new geographical areas. It is therefore critical to track this virus using genomic surveillance. However, the complex patterns of viral genomic diversity make it challenging to use the existing genotype classification system. Here we propose adding two sub-genotypic levels of virus classification, named major and minor lineages. These lineages have high thresholds for phylogenetic distance and clade size, rendering them stable between phylogenetic studies. We present an assignment tool to show that the proposed lineages are useful for regional, national and sub-national discussions of relevant DENV diversity. Moreover, the proposed lineages are robust to classification using partial genome sequences. We provide a standardized neutral descriptor of DENV diversity with which we can identify and track lineages of potential epidemiological and/or clinical importance. Information about our lineage system, including methods to assign lineages to sequence data and propose new lineages, can be found at: dengue-lineages.org.
PubMed: 38798319
DOI: 10.1101/2024.05.16.24307504 -
RNA Biology Jan 2024As positive-sense RNA viruses, the genomes of flaviviruses serve as the template for all stages of the viral life cycle, including translation, replication, and... (Review)
Review
As positive-sense RNA viruses, the genomes of flaviviruses serve as the template for all stages of the viral life cycle, including translation, replication, and infectious particle production. Yet, they encode just 10 proteins, suggesting that the structure and dynamics of the viral RNA itself helps shepherd the viral genome through these stages. Herein, we highlight advances in our understanding of flavivirus RNA structural elements through the lens of their impact on the viral life cycle. We highlight how RNA structures impact translation, the switch from translation to replication, negative- and positive-strand RNA synthesis, and virion assembly. Consequently, we describe three major themes regarding the roles of RNA structure in flavivirus infections: 1) providing a layer of specificity; 2) increasing the functional capacity; and 3) providing a mechanism to support genome compaction. While the interactions described herein are specific to flaviviruses, these themes appear to extend more broadly across RNA viruses.
Topics: Flavivirus; RNA, Viral; Virus Replication; Genome, Viral; Nucleic Acid Conformation; Humans; Flavivirus Infections; Virus Assembly; Animals; Protein Biosynthesis
PubMed: 38797925
DOI: 10.1080/15476286.2024.2357857 -
Scientific Reports May 2024A comprehensive mathematical model is proposed to study two strains of dengue virus with saturated incidence rates and quarantine measures. Imperfect dengue vaccination...
A comprehensive mathematical model is proposed to study two strains of dengue virus with saturated incidence rates and quarantine measures. Imperfect dengue vaccination is also assumed in the model. Existence, uniqueness and stability of the proposed model are proved using the results from fixed point and degree theory. Additionally, well constructed Lyapunov function candidates are also applied to prove the global stability of infection-free equilibria. It is also demonstrated that the model is generalized Ulam-Hyers stable under some appropriate conditions. The model is fitted to the real data of dengue epidemic taken from the city of Espirito Santo in Brazil. For the approximate solution of the model, a non-standard finite difference(NSFD) approach is applied. Sensitivity analysis is also carried out to show the influence of different parameters involved in the model. The behaviour of the NSFD is also assessed under different denominator functions and it is observed that the choice of the denominator function could influence the solution trajectories. Different scenario analysis are also assessed when the reproduction number is below or above one. Furthermore, simulations are also presented to assess the epidemiological impact of dengue vaccination and quarantine measures for infected individuals.
Topics: Dengue; Humans; Quarantine; Vaccination; Brazil; Dengue Virus; Models, Theoretical; Dengue Vaccines
PubMed: 38796642
DOI: 10.1038/s41598-024-62767-9