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Pathogens (Basel, Switzerland) Jun 2024(OROV) is an arbovirus transmitted by midges that has been involved in outbreaks throughout Central and South America. In Brazil, human cases have been historically...
(OROV) is an arbovirus transmitted by midges that has been involved in outbreaks throughout Central and South America. In Brazil, human cases have been historically concentrated in the northern region of the country. Oropouche fever in humans range from mild clinical signs to rare neurological events, and is considered a neglected tropical disease in Brazil. Due to the clinical similarities to other arboviruses, such as chikungunya and dengue viruses, OROV infections are likely to be underreported. Chikungunya virus (CHIKV) cases in Brazil were first recognized in 2014 in the states of Amapá and Bahia in the north and northeast regions, respectively. Both OROV and CHIKV cause nonspecific symptoms, making clinical diagnosis difficult in a scenario of arbovirus cocirculation. Aiming to investigate OROV transmission during the CHIKV introduction in the state of Amapá located in the Brazilian Amazon, we conducted a retrospective molecular (RT-qPCR) and serological investigation in febrile cases (N = 166) collected between August 2014 and May 2015. All acute serum samples were negative for OROV RNA using RT-qPCR. However, neutralizing antibodies for OROV were detected using a plaque reduction neutralization test (PRNT) in 10.24% (17/166) of the patients, with neutralizing antibody titers ranging from 20 to ≥640, suggesting the previous exposure of patients to OROV. Regarding CHIKV, recent exposure was confirmed by the detection of CHIKV RNA in 20.25% (33/163) of the patients and by the detection of anti-CHIKV IgM in 28.57% (44/154) of the patients. The additional detection of anti-CHIKV IgG in 12.58% (19/151) of the febrile patients suggests that some individuals had been previously exposed to CHIKV. Whether the OROV exposure reported here occurred prior or during the CHIKV circulation in Amapá, is unknown, but because those arboviral infections share similar clinical signs and symptoms, a silent circulation of enzootic arboviruses during the introduction of exotic arboviruses may occur, and highlights the importance of syndromic cases' surveillance to arboviruses in Brazil.
PubMed: 38921767
DOI: 10.3390/pathogens13060469 -
Pathogens (Basel, Switzerland) May 2024The Chikungunya virus (CHIKV) presents global health challenges, with Brazil experiencing outbreaks since its introduction in 2014. In 2023, following a CHIKV outbreak...
The Chikungunya virus (CHIKV) presents global health challenges, with Brazil experiencing outbreaks since its introduction in 2014. In 2023, following a CHIKV outbreak in Minas Gerais (MG), social media was used to optimize an entomological survey aimed at identifying vectors and viral lineages and assessing insecticide resistance. Following Instagram posts, residents with suspected CHIKV infection were able to schedule mosquito aspirations. In total, 421 mosquitoes (165 and 256 ) were captured from 40 households in Salinas city (MG) and tested for the Dengue, Zika, and Chikungunya viruses through RT-qPCR. Twelve of 57 pools (10 and two ) tested positive for CHIKV RNA. Viral RNA was also detected in the heads of nine , indicating viral dissemination but not in . Genome sequencing yielded the first near-complete genome from the 2023 outbreak, unveiling that the CHIKV strain belonged to the East/Central/South African (ECSA) genotype. Additionally, genetic analyses revealed high frequencies of alleles, including in CHIKV-infected mosquitoes, suggesting resistance to pyrethroid insecticides in this population. Social media was important for guiding mosquito-capture efforts in CHIKV transmission hotspots, thus optimizing the opportunity for viral detection. These findings emphasize the urgent need for innovative vector studies and control strategies, as well as interdisciplinary approaches in public health interventions.
PubMed: 38921757
DOI: 10.3390/pathogens13060457 -
Insects Jun 2024The arbovirus West Nile virus (WNV) is a danger to global health. Spread primarily by mosquitoes, WNV causes about 2000 cases per year in the United States. The natural...
The arbovirus West Nile virus (WNV) is a danger to global health. Spread primarily by mosquitoes, WNV causes about 2000 cases per year in the United States. The natural mosquito immune response controls viral replication so that the host survives but can still transmit the virus. Using the genetically malleable model, we previously dissected innate immune pathways used to control WNV infection. Specifically, we showed that insulin/IGF-1 signaling (IIS) activates a JAK/STAT-mediated immune response that reduces WNV. However, how factors that regulate IIS in insects control infection has not been identified. () encodes a peptide hormone that suppresses insulin secretion. Its mammalian ortholog, Neuromedin U (NMU), is a peptide that regulates the production and secretion of insulin from pancreatic beta cells. In this study, we used and human cell culture models to investigate the roles of these insulin regulators in immune signaling. We found that mutants, which have elevated insulin-like peptide expression, are less susceptible to WNV infection. Increased levels of insulin-like peptides in these flies result in upregulated JAK/STAT activity, leading to protection from infection. Treatment of human cells with the insulin regulator NMU results in increased WNV replication. Further investigation of methods to target Lst in mosquitoes or NMU in mammals can improve vector control methods and may lead to improved therapeutics for human and animal infection.
PubMed: 38921161
DOI: 10.3390/insects15060446 -
Parasites & Vectors Jun 2024Ticks are obligate hematophagous ectoparasites involved in transmitting viruses of public health importance. The objective of this work was to identify the Jingmen tick...
BACKGROUND
Ticks are obligate hematophagous ectoparasites involved in transmitting viruses of public health importance. The objective of this work was to identify the Jingmen tick virus in hard ticks from the Colombian Caribbean, an arbovirus of importance for public health.
METHODS
Ticks were collected in rural areas of Córdoba and Cesar, Colombia. Taxonomic identification of ticks was carried out, and pools of 13 individuals were formed. RNA extraction was performed. Library preparation was performed with the MGIEasy kit, and next-generation sequencing (NGS) with MGI equipment. Bioinformatic analyses and taxonomic assignments were performed using the Galaxy platform, and phylogenetic analyses were done using IQ-TREE2.
RESULTS
A total of 766 ticks were collected, of which 87.33% (669/766) were Rhipicephalus microplus, 5.4% (42/766) Dermacentor nitens, 4.2% (32/766) Rhipicephalus linnaei, and 3.0% (23/766) Amblyomma dissimile. Complete and partial segments 1, 2, 3, and 4 of Jingmen tick virus (JMTV) were detected in the metatranscriptome of the species R. microplus, D. nitens, and A. dissimile. The JMTVs detected are phylogenetically related to JMTVs detected in Aedes albopictus in France, JMTVs detected in R. microplus in Trinidad and Tobago, JMTVs in R. microplus and A. variegatum in the French Antilles, and JMTVs detected in R. microplus in Colombia. Interestingly, our sequences clustered closely with JMTV detected in humans from Kosovo.
CONCLUSIONS
JMTV was detected in R. microplus, D. nitens, and A. dissimile. JMTV could pose a risk to humans. Therefore, it is vital to establish epidemiological surveillance measures to better understand the possible role of JMTV in tropical diseases.
Topics: Animals; Colombia; Phylogeny; Ixodidae; Arboviruses; Caribbean Region; Female; Male; Public Health; High-Throughput Nucleotide Sequencing; Rhipicephalus; Humans; Amblyomma; Dermacentor
PubMed: 38918818
DOI: 10.1186/s13071-024-06362-x -
Neotropical Entomology Jun 2024Mosquitoes (Diptera: Culicidae) pose a significant threat to public health worldwide, especially in tropical and subtropical regions, where they act as primary vectors...
Description of New Morphological Variation of Culex (Culex) coronator Dyar and Knab, 1906 and First Report of Culex (Carrollia) bonnei Dyar, 1921 Found in the Central Region of Peru.
Mosquitoes (Diptera: Culicidae) pose a significant threat to public health worldwide, especially in tropical and subtropical regions, where they act as primary vectors in transmission of infectious agents. In Peru, 182 culicid species have been identified and several species of the genus Culex are known to transmit arboviruses. However, knowledge of mosquito diversity and distribution remains limited, with many studies focusing on specific regions only. Here, we describe a new morphological variation of Cx. (Culex) coronator Dyar and Knab, 1906, and report the presence of Culex (Carrollia) bonnei Dyar, 1921 in the central region of Peru, Huanuco. Specimens were obtained through larvae collections and identified through morphologic characterization, including dissection of male genitalia, and molecular analyses. In total, 17 mosquitoes were analyzed, and the genitalia of the male specimens allowed the identification of Cx. coronator and Cx. bonnei. Partial sequences of the CoxI gene corresponding to these two species were obtained (N = 10). Phylogenetic analysis revealed that the sequences of Cx. coronator grouped in a monophyletic clade with sequences ascribed to other species corresponding to the subgenus Carrollia, while Cx. bonnei specimens formed a monophyletic clade with homologous sequences from GenBank. This study underscores the importance of continued efforts to study the diversity and distribution of mosquitoes in Peru, including their potential role as vectors of human pathogens, to underpin effective disease control and prevention strategies, highlighting the importance of a complemented morphological and molecular analysis.
PubMed: 38918340
DOI: 10.1007/s13744-024-01160-7 -
The American Journal of Tropical... Jun 2024Phleboviruses are an emerging threat to public health. Recent surveillance efforts in Kenya have unveiled novel phleboviruses. Despite these efforts, there remain...
Phleboviruses are an emerging threat to public health. Recent surveillance efforts in Kenya have unveiled novel phleboviruses. Despite these efforts, there remain knowledge gaps. This study tested female sandflies from diverse ecological settings in Kenya for arboviruses. Sandfly pools were cultured in Vero-CCL cells. Pools showing reproducible cytopathic effects were subjected to next-generation sequencing, followed by phylogenetic analysis. In vitro, cell kinetics analysis was performed using both Vero-E6 cells and C6/36 mosquito cells. One pool from Baringo, Kenya, tested positive for Bogoria virus (BOGV). The BOGV genome clustered in a single clade with previously obtained BOGV genomes. No significant differences were observed between Vero and C6/36 cell growth kinetics. This study has confirmed the presence of BOGV among sandflies in Baringo Kenya and demonstrated growth in mosquito cells.
PubMed: 38917821
DOI: 10.4269/ajtmh.24-0032 -
PLoS Pathogens Jun 2024COVID-associated coagulopathy seemly plays a key role in post-acute sequelae of SARS- CoV-2 infection. However, the underlying pathophysiological mechanisms are poorly...
COVID-associated coagulopathy seemly plays a key role in post-acute sequelae of SARS- CoV-2 infection. However, the underlying pathophysiological mechanisms are poorly understood, largely due to the lack of suitable animal models that recapitulate key clinical and pathological symptoms. Here, we fully characterized AC70 line of human ACE2 transgenic (AC70 hACE2 Tg) mice for SARS-CoV-2 infection. We noted that this model is highly permissive to SARS-CoV-2 with values of 50% lethal dose and infectious dose as ~ 3 and ~ 0.5 TCID50 of SARS-CoV-2, respectively. Mice infected with 105 TCID50 of SARS-CoV-2 rapidly succumbed to infection with 100% mortality within 5 days. Lung and brain were the prime tissues harboring high viral titers, accompanied by histopathology. However, viral RNA and inflammatory mediators could be detectable in other organs, suggesting the nature of a systemic infection. Lethal challenge of AC70 hACE2 Tg mice caused acute onset of leukopenia, lymphopenia, along with an increased neutrophil-to-lymphocyte ratio (NLR). Importantly, infected animals recapitulated key features of COVID-19-associated coagulopathy. SARS-CoV-2 could induce the release of circulating neutrophil extracellular traps (NETs), along with activated platelet/endothelium marker. Immunohistochemical staining with anti-platelet factor-4 (PF4) antibody revealed profound platelet aggregates especially within blocked veins of the lungs. We showed that acute SARS-CoV-2 infection triggered a hypercoagulable state coexisting with ill-regulated fibrinolysis. Finally, we highlighted the potential role of Annexin A2 (ANXA2) in fibrinolytic failure. ANXA2 is a calcium-dependent phospholipid-binding protein that forms a heterotertrameric complexes localized at the extracellular membranes with two S100A10 small molecules acting as a co-receptor for tissue-plasminogen activator (t-PA), tightly involved in cell surface fibrinolysis. Thus, our results revealing elevated IgG type anti-ANXA2 antibody production, downregulated de novo ANXA2/S100A10 synthesis, and reduced ANXA2/S100A10 association in infected mice, this protein might serve as druggable targets for development of antithrombotic and/or anti-fibrinolytic agents to attenuate pathogenesis of COVID-19.
PubMed: 38913740
DOI: 10.1371/journal.ppat.1011777 -
Lancet Regional Health. Americas Jul 2024Dengue virus (DENV) is an arbovirus transmitted by mosquitoes, which can cause severe conditions such as hemorrhagic fever and dengue shock syndrome. These conditions...
BACKGROUND
Dengue virus (DENV) is an arbovirus transmitted by mosquitoes, which can cause severe conditions such as hemorrhagic fever and dengue shock syndrome. These conditions are associated with adverse social, clinical, and economic consequences in Brazil. Herein, the Wolbachia mosquito replacement method is a promising dengue control strategy.
METHODS
We estimated the economic impact of implementing the mosquito replacement method in seven Brazilian cities. A mathematical microsimulation model tracked nearly 23 million inhabitants over a 20-year period, considering the transitions between five different health states (susceptible, inapparent, outpatient, hospitalised and death). Direct costs included local dengue control programs, Wolbachia implementation and dengue care. Indirect costs related to death and productivity loss, as well as disability-adjusted life-years (DALY) averted were also considered.
FINDINGS
Without Wolbachia, the model projected 1,762,688 reported dengue cases over 20 years. Implementing the Wolbachia method would avert at least 1,295,566 dengue cases, resulting in lower costs and greater effectiveness in all simulated cities. On average, for every 1000 inhabitants followed for 20 years, the Wolbachia method yielded a cost difference of USD 538,233.68 (BRL 2,691,168.40) and averted 5.56 DALYs. Net monetary benefits (NMB) were positive in all seven cities, ranging from USD 110.72 (BRL 553.59) to USD 1399.19 (BRL 6995.95) per inhabitant. Alternative scenarios have also shown a favourable return on investment with a positive benefit-cost ratio (BCR).
INTERPRETATION
Wolbachia is likely a cost-effective strategy in the Brazilian context, consistent with international studies. Sensitivity analysis and alternative scenarios confirmed the robustness of the results.
FUNDING
This study was funded by the Wellcome Trust under a grant (224459/Z/21/Z).
PubMed: 38911346
DOI: 10.1016/j.lana.2024.100783 -
Infection, Genetics and Evolution :... Jun 2024Hainan Island and the Leizhou Peninsula, the southernmost part of mainland China, are areas where Aedes aegypti and Ae. albopictus are sympatric and are also...
BACKGROUND
Hainan Island and the Leizhou Peninsula, the southernmost part of mainland China, are areas where Aedes aegypti and Ae. albopictus are sympatric and are also high-incidence areas of dengue outbreaks in China. Many studies have suggested that Aedes endogenous viral components (EVEs) are enriched in piRNA clusters which can silence incoming viral genomes. Investigation the EVEs present in the piRNA clusters associated with viral infection of Aedes mosquitoes in these regions may provide a theoretical basis for novel transmission-blocking vector control strategies.
METHODS
In this study, specific primers for endogenous Flaviviridae elements (EFVEs) and endogenous Rhabdoviridae elements (ERVEs) were used to detect the distribution of Zika virus infection associated EVEs in the genomes of individuals of the two Aedes mosquitoes. Genetic diversity of EVEs with a high detection rate was also analyzed.
RESULTS
The results showed that many EVEs associated with Zika virus infection were detected in both Aedes species, with the detection rates were 47.68% to 100% in Ae. aegypti and 36.15% to 92.31% in sympatric Ae. albopictus populations. EVEs detection rates in another 17 Ae. albopictus populations ranged from 29.39% to 89.85%. Genetic diversity analyses of the four EVEs (AaFlavi53, AaRha61, AaRha91 and AaRha100) of Ae. aegypti showed that each had high haplotype diversity and low nucleotide diversity. The number of haplotypes in AaFlavi53 was 8, with the dominant haplotype being Hap_1 and the other 7 haplotypes being further mutated from Hap_1 in a lineage direction. In contrast, the haplotype diversity of the other three ERVEs (AaRha61, AaRha91 and AaRha100) was more diverse and richer, with the haplotype numbers were 9, 15 and 19 respectively. In addition, these EVEs all showed inconsistent patterns of both population differentiation and dispersal compared to neutral evolutionary genes such as the Mitochondrial COI gene.
CONCLUSION
The EFVEs and ERVEs tested were present at high frequencies in the field Aedes mosquito populations. The haplotype diversity of the EFVE AaFlavi53 was relatively lower and the three ERVEs (AaRha61, AaRha91, AaRha100) were higher. None of the four EVEs could be indicative of the genetic diversity of the Ae. aegypti population. This study provided theoretical support for the use of EVEs to block arbovirus transmission, but further research is needed into the mechanisms by which these EVEs are antiviral to Aedes mosquitoes.
PubMed: 38909667
DOI: 10.1016/j.meegid.2024.105627 -
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