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Frontiers in Immunology 2024The mitochondrial anti-viral signaling (MAVS) protein is an intermediary adaptor protein of retinoic acid-inducible gene-1 (RIG-I) like receptor (RLR) signaling, which...
MAVS disruption impairs downstream signaling and results in higher virus replication levels of salmonid alphavirus subtype 3 but not infectious pancreatic necrosis virus .
The mitochondrial anti-viral signaling (MAVS) protein is an intermediary adaptor protein of retinoic acid-inducible gene-1 (RIG-I) like receptor (RLR) signaling, which activates the transcription factor interferon (IFN) regulatory factor 3 (IRF3) and NF-kB to produce type I IFNs. MAVS expression has been reported in different fish species, but few studies have shown its functional role in anti-viral responses to fish viruses. In this study, we used the transcription activator-like effector nuclease (TALEN) as a gene editing tool to disrupt the function of MAVS in Chinook salmon () embryonic cells (CHSE) to understand its role in induction of interferon I responses to infections with the (+) RNA virus salmonid alphavirus subtype 3 (SAV-3), and the dsRNA virus infectious pancreatic necrosis virus (IPNV) infection. A MAVS-disrupted CHSE clone with a 7-aa polypeptide (GVFVSRV) deletion mutation at the N-terminal of the CARD domain infected with SAV-3 resulted in significantly lower expression of IRF3, IFNa, and ISGs and increased viral titer (1.5 log) compared to wild-type. In contrast, the IPNV titer in MAVS-disrupted cells was not different from the wild-type. Furthermore, overexpression of salmon MAVS in MAVS-disrupted CHSE cells rescued the impaired type I IFN-mediated anti-viral effect against SAV-3.
Topics: Animals; Infectious pancreatic necrosis virus; Alphavirus; Virus Replication; Signal Transduction; Adaptor Proteins, Signal Transducing; Fish Diseases; Alphavirus Infections; Salmon; Fish Proteins; Interferon Regulatory Factor-3; Birnaviridae Infections
PubMed: 38903507
DOI: 10.3389/fimmu.2024.1401086 -
Trials Jun 2024This trial is a parallel, two-arm, non-blinded cluster randomised controlled trial that is under way in Singapore, with the aim of measuring the efficacy of male...
BACKGROUND
This trial is a parallel, two-arm, non-blinded cluster randomised controlled trial that is under way in Singapore, with the aim of measuring the efficacy of male Wolbachia-infected Aedes aegypti deployments in reducing dengue incidence in an endemic setting with all four dengue serotypes in circulation. The trial commenced in July 2022 and is expected to conclude in September 2024. The original study protocol was published in December 2022. Here, we describe amendments that have been made to the study protocol since commencement of the trial.
METHODS
The key protocol amendments are (1) addition of an explicit definition of Wolbachia exposure for residents residing in intervention sites based on the duration of Wolbachia exposure at point of testing, (2) incorporation of a high-dimensional set of anthropogenic and environmental characteristics in the analysis plan to adjust for baseline risk factors of dengue transmission, and (3) addition of alternative statistical analyses for endpoints to control for post hoc imbalance in cluster-based environmental and anthropogenic characteristics.
DISCUSSION
The findings from this study will provide the first experimental evidence for the efficacy of releasing male-Wolbachia infected mosquitoes to reduce dengue incidence in a cluster-randomised controlled trial. The trial will conclude in 2024 and results will be reported shortly thereafter.
TRIAL REGISTRATION
ClinicalTrials.gov, identifier: NCT05505682. Registered on 16 August 2022. Retrospectively registered. Last updated 11 November 2023.
Topics: Dengue; Animals; Wolbachia; Singapore; Male; Aedes; Humans; Incidence; Mosquito Vectors; Randomized Controlled Trials as Topic; Mosquito Control; Female; Pest Control, Biological
PubMed: 38902790
DOI: 10.1186/s13063-024-08148-z -
Virology Journal Jun 2024Despite dengue virus (DENV) outbreak in Gabon a decade ago, less is known on the potential circulation of DENV serotypes in the country. Previous studies conducted in...
BACKGROUND
Despite dengue virus (DENV) outbreak in Gabon a decade ago, less is known on the potential circulation of DENV serotypes in the country. Previous studies conducted in some areas of the country, are limited to hospital-based surveys which reported the presence of some cases of serotype 2 and 3 seven years ago and more recently the serotype 1. As further investigation, we extend the survey to the community of Moyen Ogooué region with the aim to assess the presence of the dengue virus serotypes, additionally to characterize chikungunya (CHIKV) infection and describe the symptomatology associated with infections.
METHOD
A cross-sectional survey was conducted from April 2020 to March 2021. The study included participants of both sexes and any age one year and above, with fever or history of fever in the past seven days until blood collection. Eligible volunteers were clinically examined, and blood sample was collected for the detection of DENV and CHIKV using RT-qPCR. Positive samples were selected for the target sequencing.
RESULTS
A total of 579 volunteers were included. Their mean age (SD) was 20 (20) years with 55% of them being female. Four cases of DENV infection were diagnosed giving a prevalence of 0.7% (95%CI: 0.2-1.8) in our cohort while no case of CHIKV was detected. The common symptoms and signs presented by the DENV cases included fatigue, arthralgia myalgia, cough, and loss of appetite. DENV-1was the only virus detected by RT-qPCR.
CONCLUSION
Our results confirm the presence of active dengue infection in the region, particularly DENV-1, and could suggest the decline of DENV-2 and DENV-3. Continuous surveillance remains paramount to comprehensively describe the extent of dengue serotypes distribution in the Moyen-Ogooué region of Gabon.
Topics: Humans; Gabon; Dengue Virus; Female; Male; Dengue; Serogroup; Cross-Sectional Studies; Adult; Young Adult; Adolescent; Child, Preschool; Child; Middle Aged; Infant; Chikungunya Fever; Aged; Prevalence; Chikungunya virus
PubMed: 38902719
DOI: 10.1186/s12985-024-02406-x -
BMC Public Health Jun 2024Aedes mosquitoes are the main vector of dengue infection, a global health threat affecting millions of people annually. Conventional prevention and control methods...
BACKGROUND
Aedes mosquitoes are the main vector of dengue infection, a global health threat affecting millions of people annually. Conventional prevention and control methods against dengue outbreaks have only achieved marginal success. Recognizing the complex issue at hand, a multilevel participatory approach is crucial. Thus, alternative strategies that involve community engagement are increasingly being considered and attempted. While community-based vector control programs have been conducted, sustaining behavioral changes among the population remains a challenge. This study aimed to identify the specific community needs in combating Aedes mosquitoes and dengue fever as a basis to guide the development of community-driven initiatives and foster a deeper sense of ownership in the fight against dengue.
METHODS
Between 1 August 2022 and 30 November 2022, we conducted a study in Hulu Langat district, Selangor, using a mixed-method design. All participants consented to the study, which comprised 27 participants (FGDs) and 15 participants (IDIs). The IDIs included two participants with a history of dengue fever, one community leader, one faith leader, seven local authorities, and four district health officers. Semi-structured interviews and discussions were performed among stakeholders and community members recruited via purposive and snowball sampling techniques. All interviews were audio-recorded before being analyzed using reflexive thematic analysis.
RESULTS
These results derived from qualitative data explored the perspectives and needs of communities in combating Aedes mosquitoes and dengue fever. Interviews were conducted with various stakeholders, including community members, leaders, and health officers. The study identified the necessity of decisive actions by authorities to address the impact of the dengue epidemic, the importance of community engagement through partnerships and participatory approaches, the potential benefits of incentives and rewards to enhance community participation, and the need for sustained community engagement and education, especially via the involvement of young people in prevention efforts. These findings provide valuable insights into the design of effective strategies against Aedes mosquitoes and dengue fever.
CONCLUSIONS
In short, there is an urgent need for a comprehensive approach involving multiple stakeholders in the fight against Aedes mosquitoes and dengue fever. The approach should incorporate efforts to raise awareness, provide practical resources, and foster community responsibility. The active involvement of teenagers as volunteers can contribute to long-term prevention efforts. Collaboration, resource allocation, and community engagement are crucial for effective dengue control and a healthier environment.
Topics: Humans; Aedes; Dengue; Animals; Female; Male; Adult; Mosquito Control; Community Participation; Urban Population; Middle Aged; Mosquito Vectors; Indonesia; Qualitative Research; Needs Assessment; Health Knowledge, Attitudes, Practice; Young Adult
PubMed: 38902692
DOI: 10.1186/s12889-024-18965-1 -
Revista Da Sociedade Brasileira de... 2024Dengue is a disease that accounts for a major morbidity and mortality in Honduras.
BACKGROUND
Dengue is a disease that accounts for a major morbidity and mortality in Honduras.
METHODS
This descriptive study used an analytical component based on the data from the National Virology Laboratory between 2016-2022. Ordinal logistic regression was used to identify the factors associated with the classification of dengue without warning signs (DWOS), dengue with warning signs (DWS), and severe dengue (SD).
RESULTS
Overall, 14,687 dengue cases were included; 50.1% had DWOS, 36.5% had DWS, and 13.4% had SD. Patients that were more associated with a higher probability of DWS and SD were patients in the age groups 1-4 years (DWS OR 1.61; 95%CI:1.33-1.94), (SD OR 1.52; 95% CI:1.26-1.84), 5-9 years (DWS OR 2.01; 95% CI:1.68-2.40), (SD OR 2.00; 95% CI:1.67-2.40), and 10-19 years (DWS OR 1.55; 95% CI:1.30-1.85) (SD OR 1.57; 95% CI:1.31-1.88). The departments that were associated with a higher probability of DWS and SD were La Paz (OR 6.35; 95% CI:3.53-11.42), (OR 10.94; 95% CI:5.96-20.08), Copán (OR 6.94; 95% CI:5.05-9.53) (OR 7.33; 95% CI: 5.35-10.03), Valle (OR 5.22; 95% CI:1.25-21.82) (OR 10.71; 95% CI:2.21-51.88).
CONCLUSIONS
During the study period, dengue presented endemic behavior, with peaks consistent with the last two epidemics in Honduras in 2015 and 2019. The main factors associated with dengue severity were age< 19 years, male sex, and being from La Paz, Copán, or Valle.
Topics: Humans; Honduras; Male; Adolescent; Child; Female; Dengue; Adult; Young Adult; Child, Preschool; Severity of Illness Index; Infant; Middle Aged; Risk Factors; Severe Dengue
PubMed: 38896654
DOI: 10.1590/0037-8682-0594-2023 -
Revista Brasileira de Epidemiologia =... 2024To estimate the cost of illness of Chikungunya in the municipality of Rio de Janeiro, Brazil, in 2019.
OBJECTIVE
To estimate the cost of illness of Chikungunya in the municipality of Rio de Janeiro, Brazil, in 2019.
METHODS
The study is a partial economic evaluation carried out with secondary data with free and unrestricted access. Direct outpatient and indirect costs of the acute, post-acute, and chronic phases of Chikungunya fever were estimated, in addition to hospital costs. The estimate of direct costs was performed using the notified cases and the standard treatment flowchart in the state of Rio de Janeiro. The indirect ones consist of loss of productivity and disability, using the burden of disease indicator (Disability-adjusted life year - DALY).
RESULTS
The total number of reported cases was 38,830. Total costs were calculated at BRL 279,807,318, with 97% related to indirect costs.
CONCLUSION
The chronic phase and indirect costs were the most expensive. The inability and permanence of Chikungunya differentiate the disease and increase the costs of its treatment.
Topics: Chikungunya Fever; Brazil; Humans; Cost of Illness; Adult; Male; Female; Adolescent; Middle Aged; Young Adult; Child; Child, Preschool; Health Care Costs; Infant; Aged
PubMed: 38896647
DOI: 10.1590/1980-549720240026 -
Revista Brasileira de Epidemiologia =... 2024To analyze the transmission dynamics of dengue, a public health problem in Brazil and the Metropolitan Region of Belo Horizonte (MRBH).
OBJECTIVE
To analyze the transmission dynamics of dengue, a public health problem in Brazil and the Metropolitan Region of Belo Horizonte (MRBH).
METHODS
The spatiotemporal evolution of the occurrence of dengue in the municipality of Contagem, state of Minas Gerais, a region with high arbovirus transmission, was analyzed. Furthermore, epidemic and non-epidemic periods were analyzed, based on probable cases of dengue. This is an ecological study that used the Notifiable Diseases Information System (SINAN) national database. The analyses were carried out considering the period from epidemiological week (EW) 40 of 2011 to 39 of 2017. Spatial analysis tools (crude and smoothed incidence rate, directional distribution ellipse, global Moran index and local Moran index, and spatial scanning time with definition of epidemiological risk) were used.
RESULTS
The 2012 to 2013 and 2015 to 2016 epidemic cycles presented high incidence rates. The disease was concentrated in more urbanized areas, with a small increase in cases throughout the municipality. Seven statistically significant local clusters and areas with a high rate of cases and accentuated transmission in epidemic cycles were observed throughout the municipality. Spatial autocorrelation of the incidence rate was observed in all periods.
CONCLUSION
The results of the present study highlight a significant and heterogeneous increase in dengue notifications in Contagem over the years, revealing distinct spatial patterns during epidemic and non-epidemic periods. Geoprocessing analysis identified high-risk areas, a piece of knowledge that can optimize the allocation of resources in the prevention and treatment of the disease for that municipality.
Topics: Humans; Dengue; Brazil; Incidence; Epidemics; Spatio-Temporal Analysis; Cities; Time Factors; Disease Notification
PubMed: 38896646
DOI: 10.1590/1980-549720240023 -
Frontiers in Cellular and Infection... 2024Chikungunya virus (CHIKV), which causes chikungunya fever, is an arbovirus of public health concern with no approved antiviral therapies. A significant proportion of...
BACKGROUND
Chikungunya virus (CHIKV), which causes chikungunya fever, is an arbovirus of public health concern with no approved antiviral therapies. A significant proportion of patients develop chronic arthritis after an infection. Zinc and magnesium salts help the immune system respond effectively against viral infections. This study explored the antiviral potential of zinc sulphate, zinc acetate, and magnesium sulphate against CHIKV infection.
METHODS
The highest non-toxic concentration of the salts (100 µM) was used to assess the prophylactic, virucidal, and therapeutic anti-CHIKV activities. Dose-dependent antiviral effects were investigated to find out the 50% inhibitory concentration of the salts. Entry bypass assay was conducted to find out whether the salts affect virus entry or post entry stages. Virus output in all these experiments was estimated using a focus-forming unit assay, real-time RT-PCR, and immunofluorescence assay.
RESULTS
Different time- and temperature-dependent assays revealed the therapeutic antiviral activity of zinc and magnesium salts against CHIKV. A minimum exposure of 4 hours and treatment initiation within 1 to 2 hours of infection are required for inhibition of CHIKV. Entry assays revealed that zinc salt affected virus-entry. Entry bypass assays suggested that both salts affected post-entry stages of CHIKV. In infected C57BL6 mice orally fed with zinc and magnesium salts, a reduction in viral RNA copy number was observed.
CONCLUSION
The study results suggest zinc salts exert anti-CHIKV activity at entry and post entry stages of the virus life cycle, while magnesium salt affect CHIKV at post entry stages. Overall, the study highlights the significant antiviral potential of zinc sulphate, zinc acetate, and magnesium sulphate against CHIKV, which can be exploited in designing potential therapeutic strategies for early treatment of chikungunya patients, thereby reducing the virus-associated persistent arthritis.
Topics: Chikungunya virus; Animals; Antiviral Agents; Chikungunya Fever; Zinc Acetate; Zinc Sulfate; Chlorocebus aethiops; Vero Cells; Virus Internalization; Mice; Zinc; Humans; Magnesium Sulfate; Magnesium; Virus Replication; Inhibitory Concentration 50; Salts; Cell Line
PubMed: 38895735
DOI: 10.3389/fcimb.2024.1335189 -
Molecules (Basel, Switzerland) May 2024Within the fields of infectious disease diagnostics, microfluidic-based integrated technology systems have become a vital technology in enhancing the rapidity, accuracy,... (Review)
Review
Within the fields of infectious disease diagnostics, microfluidic-based integrated technology systems have become a vital technology in enhancing the rapidity, accuracy, and portability of pathogen detection. These systems synergize microfluidic techniques with advanced molecular biology methods, including reverse transcription polymerase chain reaction (RT-PCR), loop-mediated isothermal amplification (LAMP), and clustered regularly interspaced short palindromic repeats (CRISPR), have been successfully used to identify a diverse array of pathogens, including COVID-19, Ebola, Zika, and dengue fever. This review outlines the advances in pathogen detection, attributing them to the integration of microfluidic technology with traditional molecular biology methods and smartphone- and paper-based diagnostic assays. The cutting-edge diagnostic technologies are of critical importance for disease prevention and epidemic surveillance. Looking ahead, research is expected to focus on increasing detection sensitivity, streamlining testing processes, reducing costs, and enhancing the capability for remote data sharing. These improvements aim to achieve broader coverage and quicker response mechanisms, thereby constructing a more robust defense for global public health security.
Topics: Humans; Nucleic Acid Amplification Techniques; Molecular Diagnostic Techniques; Microfluidics; Communicable Diseases; COVID-19; SARS-CoV-2; Microfluidic Analytical Techniques; Dengue; Zika Virus Infection; Zika Virus
PubMed: 38893293
DOI: 10.3390/molecules29112417 -
Nature Communications Jun 2024Zika virus (ZikV) infection during pregnancy can cause congenital Zika syndrome (CZS) and neurodevelopmental delay in infants, of which the pathogenesis remains poorly...
Zika virus (ZikV) infection during pregnancy can cause congenital Zika syndrome (CZS) and neurodevelopmental delay in infants, of which the pathogenesis remains poorly understood. We utilize an established female pigtail macaque maternal-to-fetal ZikV infection/exposure model to study fetal brain pathophysiology of CZS manifesting from ZikV exposure in utero. We find prenatal ZikV exposure leads to profound disruption of fetal myelin, with extensive downregulation in gene expression for key components of oligodendrocyte maturation and myelin production. Immunohistochemical analyses reveal marked decreases in myelin basic protein intensity and myelinated fiber density in ZikV-exposed animals. At the ultrastructural level, the myelin sheath in ZikV-exposed animals shows multi-focal decompaction, occurring concomitant with dysregulation of oligodendrocyte gene expression and maturation. These findings define fetal neuropathological profiles of ZikV-linked brain injury underlying CZS resulting from ZikV exposure in utero. Because myelin is critical for cortical development, ZikV-related perturbations in oligodendrocyte function may have long-term consequences on childhood neurodevelopment, even in the absence of overt microcephaly.
Topics: Animals; Zika Virus Infection; Oligodendroglia; Female; Myelin Sheath; Pregnancy; Zika Virus; Disease Models, Animal; Pregnancy Complications, Infectious; Macaca nemestrina; Brain; Humans; Myelin Basic Protein
PubMed: 38890352
DOI: 10.1038/s41467-024-49524-2