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1.
Braz. j. biol ; 83: e240118, 2023. tab, graf
Artículo en Inglés | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1278559

RESUMEN

Abstract For many centuries human populations have been suffering and trying to fight with disease-bearing mosquitoes. Emerging and reemerging diseases such as Dengue, Zika, and Chikungunya affect billions of people around the world and recently has been appealing to control with chemical pesticides. Malathion (MT) is one of the main pesticides used against mosquitoes, the vectors of these diseases. This study aimed to assess cytotoxicity and mutagenicity of the malathion for the bioindicator Allium cepa L. using a multivariate and integrative approach. Moreover, an appendix table was compiled with all available literature of insecticides assessed by the Allium cepa system to support our discussion. Exposures during 48h to 0.5 mg mL-1 and 1.0 mg mL-1 MT were compared to the negative control (distilled water) and positive control (MMS solution at 10 mg L-1). The presence of chromosomal aberrations, micronuclei frequency, and mitotic index abnormalities was evaluated. Anaphase bridges were the alterations with higher incidence and presented a significantly elevated rate in the concentration of 0.5 mg mL-1, including when compared to the positive control. The integrative discriminant analysis summarizes that MT in assessed concentrations presented effects like the positive control, corroborating its potential of toxicity to DNA. Therefore, it is concluded that MT in its pure composition and in realistic concentrations used, has genotoxic potential in the biological assessment of A. cepa cells. The multivariate integrative analysis was fundamental to show a whole response of all data, providing a global view of the effect of MT on DNA.


Resumo Por muitos séculos, as populações humanas sofrem e tentam combater os mosquitos transmissores de doenças. Doenças emergentes e reemergentes como Dengue, Zika e Chikungunya afetam bilhões de pessoas em todo o mundo e, recentemente, vem apelando ao controle com pesticidas químicos. O Malation (MT) é um dos principais pesticidas usados ​​contra mosquitos, vetores dessas doenças. O objetivo deste estudo foi avaliar a citotoxicidade e a mutagenicidade do MT para o bioindicador Allium cepa L. usando uma abordagem multivariada e integrativa. Além disso, uma tabela suplementar foi compilada com toda a literatura disponível de inseticidas avaliada pelo sistema Allium cepa para apoiar nossa discussão. Exposições ao MT durante 48h a 0,5 mg mL-1 e 1,0 mg mL-1 foram comparadas a um controle negativo (água destilada) e um controle positivo (10 mg L-1 de MMS). Foram avaliadas a presença de aberrações cromossômicas, frequência de micronúcleos e anormalidades no índice mitótico. As pontes anafásicas foram as alterações com maior incidência e apresentaram uma taxa significativamente elevada na concentração de 0,5 mg mL-1, inclusive quando comparadas ao controle positivo. A análise discriminante integrativa resume que o MT nas concentrações avaliadas apresentou efeitos semelhantes ao controle positivo, corroborando seu potencial de toxicidade para o DNA. Portanto, conclui-se que o MT, em sua composição pura e nas concentrações realistas utilizadas, possui potencial genotóxico na avaliação biológica de células de A. cepa. A análise integrativa multivariada foi fundamental para mostrar uma resposta completa de todos os dados, fornecendo uma visão global do efeito da MT no DNA.

2.
J Ethnopharmacol ; 282: 114627, 2022 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-34509603

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Dengue virus (DENV) is a re-emerging mosquito-borne flavivirus that has recently engendered large epidemics around the world. Consequently antivirals with effective anti-DENV therapeutic activity are urgently required. In the 18th century, Europeans, as well as native inhabitants of North America, were known to adapt the medicinal property of the common perennial plant Eupatorium perfoliatum L. to treat fever and infections. Previous studies have shown that Eupatorium perfoliatum L. possesses anti-inflammatory, anti-oxidative, anti-plasmodial, anti-bacterial and antiviral activities. However, to the best of our knowledge, no anti-DENV activity of E. perfoliatum L. has been investigated at the molecular level so far. AIM OF STUDY: Here, for the first time we have attempted to study the action of E. perfoliatum extract and its few bioactive components i.e., quercetin, caffeic acid and eupafolin against wild primary clinical isolate of DENV-2 infection in an in vitro model. MATERIALS AND METHODS: The presence of the bioactive components in the E. perfoliatum extract, were analyzed by HPLC- DAD. Then, CC50 as well as IC50 values of the extract and its bioactive components were measured against DENV in HepG2 cell line. After that, the antiviral activity was studied by Time of addition assay using qRT-PCR. Further, the downstream signalling action of E. perfoliatum extract, was studied by Human phosphorylation MAPK antibody array, followed by immunofluorescence microscopy. Moreover, a molecular docking analysis was done to study the binding affinity of bioactive components of E. perfoliatum extract with TIM-1 transmembrane receptor protein, which is known for viral internalization. RESULT: We found that E. perfoliatum extract has marked antiviral activity during pre-treatment against DENV infection in HepG2 cell line. The extract also significantly reduced the DENV induced autophagy in HepG2 cell line as detected by LC3 II localization. The presence of different bioactive compounds in E. perfoliatum extract were confirmed by HPLC-DAD. In the bioactive components, in parallel to earlier studies, quercetin showed the most significant preventive action against DENV infection. Further, in molecular docking analysis also, quercetin showed the strongest binding affinity towards DENV membrane receptor TIM-1 protein. CONCLUSION: Our findings suggests that E. perfoliatum extract has significant potential to be an anti-DENV therapeutic agent. Moreover, among the bioactive components, quercetin may have a prophylaxis role in executing the antiviral activity of E. perfoliatum extract against DENV infection.

3.
San Salvador; MINSAL; oct. 05, 2021. 23 p. ilus, graf, tab, mapas.
No convencional en Español | LILACS, BISSAL | ID: biblio-1293157

RESUMEN

Resumen de eventos de notificación hasta SE 38/2021. Alertas internacionales. Situación epidemiológica de dengue. Situación epidemiológica de zika y chikungunya. Infección respiratoria aguda. Neumonías. Situación mundial del 2019-nCov (OMS. Vigilancia centinela de influenza y otros virus respiratorios. Vigilancia centinela de rotavirus. Enfermedad diarreica aguda


Summary of notification events up to SE 38/2021. International alerts. Epidemiological situation of dengue. Epidemiological situation of Zika and Chikungunya. Acute respiratory infection. Pneumonia Global situation 2019-nCov (WHO. Sentinel surveillance of influenza and other respiratory viruses. Sentinel surveillance for rotavirus. Acute diarrheal Disease


Asunto(s)
Epidemiología , Publicaciones Electrónicas , COVID-19
4.
Sci Rep ; 11(1): 19707, 2021 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-34611250

RESUMEN

Dengue poses a global health threat, which will persist without therapeutic intervention. Immunity induced by exposure to one serotype does not confer long-term protection against secondary infection with other serotypes and is potentially capable of enhancing this infection. Although vaccination is believed to induce durable and protective responses against all the dengue virus (DENV) serotypes in order to reduce the burden posed by this virus, the development of a safe and efficacious vaccine remains a challenge. Immunoinformatics and computational vaccinology have been utilized in studies of infectious diseases to provide insight into the host-pathogen interactions thus justifying their use in vaccine development. Since vaccination is the best bet to reduce the burden posed by DENV, this study is aimed at developing a multi-epitope based vaccines for dengue control. Combined approaches of reverse vaccinology and immunoinformatics were utilized to design multi-epitope based vaccine from the sequence of DENV. Specifically, BCPreds and IEDB servers were used to predict the B-cell and T-cell epitopes, respectively. Molecular docking was carried out using Schrödinger, PATCHDOCK and FIREDOCK. Codon optimization and in silico cloning were done using JCAT and SnapGene respectively. Finally, the efficiency and stability of the designed vaccines were assessed by an in silico immune simulation and molecular dynamic simulation, respectively. The predicted epitopes were prioritized using in-house criteria. Four candidate vaccines (DV-1-4) were designed using suitable adjuvant and linkers in addition to the shortlisted epitopes. The binding interactions of these vaccines against the receptors TLR-2, TLR-4, MHC-1 and MHC-2 show that these candidate vaccines perfectly fit into the binding domains of the receptors. In addition, DV-1 has a better binding energies of - 60.07, - 63.40, - 69.89 kcal/mol against MHC-1, TLR-2, and TLR-4, with respect to the other vaccines. All the designed vaccines were highly antigenic, soluble, non-allergenic, non-toxic, flexible, and topologically assessable. The immune simulation analysis showed that DV-1 may elicit specific immune response against dengue virus. Moreover, codon optimization and in silico cloning validated the expressions of all the designed vaccines in E. coli. Finally, the molecular dynamic study shows that DV-1 is stable with minimum RMSF against TLR4. Immunoinformatics tools are now applied to screen genomes of interest for possible vaccine target. The designed vaccine candidates may be further experimentally investigated as potential vaccines capable of providing definitive preventive measure against dengue virus infection.

5.
BMC Public Health ; 21(1): 1843, 2021 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-34641853

RESUMEN

BACKGROUND: Outbreaks 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. METHODS: This is a mixed method study of a cross-sectional design, in which qualitative in-depth interviews and quantitative household questionnaire surveys are included. RESULTS: Questionnaire 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. CONCLUSION: The 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.

6.
mSphere ; : e0055121, 2021 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-34643419

RESUMEN

Vector-borne diseases (VBDs) cause enormous health burden worldwide, as they account for more than 17% of all infectious diseases and over 700,000 deaths each year. A significant number of these VBDs are caused by RNA virus pathogens. Here, we used metagenomics and metabarcoding analysis to characterize RNA viruses and their insect hosts among biting midges from Kenya. We identified a total of 15 phylogenetically distinct insect-specific viruses. These viruses fall into six families, with one virus falling in the recently proposed negevirus taxon. The six virus families include Partitiviridae, Iflaviridae, Tombusviridae, Solemoviridae, Totiviridae, and Chuviridae. In addition, we identified many insect species that were possibly associated with the identified viruses. Ceratopogonidae was the most common family of midges identified. Others included Chironomidae and Cecidomyiidae. Our findings reveal a diverse RNA virome among Kenyan midges that includes previously unknown viruses. Further, metabarcoding analysis based on COI (cytochrome c oxidase subunit 1 mitochondrial gene) barcodes reveal a diverse array of midge species among the insects used in the study. Successful application of metagenomics and metabarcoding methods to characterize RNA viruses and their insect hosts in this study highlights a possible simultaneous application of these two methods as cost-effective approaches to virus surveillance and host characterization. IMPORTANCE The majority of the viruses that currently cause diseases in humans and animals are RNA viruses, and more specifically arthropod-transmitted viruses. They cause diseases such as dengue, West Nile infection, bluetongue disease, Schmallenberg disease, and yellow fever, among others. Several sequencing investigations have shown us that a diverse array of RNA viruses among insect vectors remain unknown. Some of these could be ancient lineages that could aid in comprehensive studies on RNA virus evolution. Such studies may provide us with insights into the evolution of the currently pathogenic viruses. Here, we applied metagenomics to field-collected midges and we managed to characterize several RNA viruses, where we recovered complete and nearly complete genomes of these viruses. We also characterized the insect host species that are associated with these viruses. These results add to the currently known diversity of RNA viruses among biting midges as well as their associated insect hosts.

7.
J Virol ; : JVI0166521, 2021 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-34643435

RESUMEN

Zinc-finger protein 36, CCCH type-like 1 (ZFP36L1), containing tandem CCCH-type zinc-finger motifs with an RNA-binding property, plays an important role in cellular RNA metabolism mainly via RNA decay pathways. Recently, we demonstrated that human ZFP36L1 has potent antiviral activity against influenza A virus infection. However, its role in the host defense response against flaviviruses has not been addressed. Here, we demonstrate that ZFP36L1 functions as a host innate defender against flaviviruses, including Japanese encephalitis virus (JEV) and dengue virus (DENV). Overexpression of ZFP36L1 reduced JEV and DENV infection, and ZFP36L1 knockdown enhanced viral replication. ZFP36L1 destabilized the JEV genome by targeting and degrading viral RNA mediated by both 5'-3' XRN1 and 3'-5' RNA-exosome RNA decay pathways. Mutation in both zinc-finger motifs of ZFP36L1 disrupted RNA-binding and antiviral activity. Furthermore, the viral RNA sequences specifically recognized by ZFP36L1 were mapped to the 3'-untranslated region of the JEV genome with the AU-rich element (AUUUA) motif. We extend the function of ZFP36L1 to host antiviral defense by directly binding and destabilizing the viral genome via recruiting cellular mRNA decay machineries. Importance Cellular RNA-binding proteins are among the first lines of defense against various viruses, particularly RNA viruses. ZFP36L1 belongs to the CCCH-type zinc-finger protein family and has RNA-binding activity; it has been reported to directly bind to the AU-rich elements (AREs) of a subset of cellular mRNAs and then lead to mRNA decay by recruiting mRNA degrading enzymes. However, the antiviral potential of ZFP36L1 against flaviviruses has not yet been fully demonstrated. Here, we reveal the antiviral potential of human ZFP36L1 against Japanese encephalitis virus (JEV) and dengue virus (DENV). ZFP36L1 specifically targeted the ARE motif within viral RNA and triggered the degradation of viral RNA transcripts via cellular degrading enzymes, 5'-3' XRN1 and 3'-5' RNA exosome. These findings provide mechanistic insights into how human ZFP36L1 serves as a host antiviral factor to restrict flavivirus replication.

8.
Bioorg Med Chem ; 49: 116415, 2021 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-34601454

RESUMEN

Dengue remains a disease of significant concern, responsible for nearly half of all arthropod-borne disease cases across the globe. Due to the lack of potent and targeted therapeutics, palliative treatment and the adoption of preventive measures remain the only available options. Compounding the problem further, the failure of the only dengue vaccine, Dengvaxia®, also delivered a significant blow to any hopes for the treatment of dengue fever. However, the success of Human Immuno-deficiency Virus (HIV) and Hepatitis C Virus (HCV) protease inhibitors in the past have continued to encourage researchers to investigate other viral protease targets. Dengue virus (DENV) NS2B-NS3 protease is an attractive target partly due to its role in polyprotein processing and also for being the most conserved domain in the viral genome. During the early days of the COVID-19 pandemic, a few cases of Dengue-COVID 19 co-infection were reported. In this review, we compared the substrate-peptide residue preferences and the residues lining the sub-pockets of the proteases of these two viruses and analyzed the significance of this similarity. Also, we attempted to abridge the developments in anti-dengue drug discovery in the last six years (2015-2020), focusing on critical discoveries that influenced the research.

10.
PLoS One ; 16(10): e0258388, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34624062

RESUMEN

INTRODUCTION: The cost in managing hospitalised dengue patients varies across countries depending on access to healthcare, management guidelines, and state sponsored subsidies. For health budget planning, locally relevant, accurate costing data from prospective studies, is essential. OBJECTIVE: To characterise the direct costs of managing hospitalised patients with suspected dengue infection in Sri Lanka. METHODS: Colombo Dengue Study is a prospective single centre cohort study in Sri Lanka recruiting suspected hospitalised dengue fever patients in the first three days of fever and following them up until discharge. The diagnosis of dengue is retrospectively confirmed and the cohort therefore has a group of non-dengue fever patients with a phenotypically similar illness, managed as dengue while in hospital. The direct costs of hospital admission (base and investigation costs, excluding medication) were calculated for all recruited patients and compared between dengue and non-dengue categories as well as across subgroups (demographic, clinical or temporal) within each of these categories. We also explored if excluding dengue upfront, would lead to an overall cost saving in several hypothetical scenarios. RESULTS: From October 2017 to February 2020, 431 adult dengue patients and 256 non-dengue fever patients were recruited. The hospitalisation costs were USD 18.02 (SD: 4.42) and USD 17.55 (SD: 4.09) per patient per day for dengue and non-dengue patients respectively (p>0.05). Laboratory investigations (haematological, biochemical and imaging) accounted for more than 50% of the total cost. The costs were largely homogenous in all subgroups within or across dengue and non-dengue categories. Excluding dengue upfront by subsidised viral genomic testing may yield overall cost savings for non-dengue patients. CONCLUSION: As non-dengue patients incur a similar cost per day as the dengue patients, confirming dengue diagnosis using subsidised tests for patients presenting in the first three days of fever may be cost-efficient.

11.
Parasit Vectors ; 14(1): 520, 2021 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-34625096

RESUMEN

BACKGROUND: Sugar feeding is a fundamental behaviour of many mosquito species. For Aedes albopictus, an important vector of dengue virus and chikungunya virus, little is known about its sugar-feeding behaviour, and no studies have been conducted on this in the southern hemisphere. This knowledge is pivotal for determining the potential of attractive targeted sugar baits (ATSBs) to control this important vector. METHODS: The prevalence of sugar was assessed in 1808 Ae. albopictus from Masig Island, Torres Strait, Australia collected between 13 and 25 March 2020. Fructose presence and content in field-collected Ae. albopictus were quantified using the cold anthrone assay. RESULTS: Significantly more male (35.8%) than female (28.4%) Ae. albopictus were sugar fed. There was a significant interaction between sex and time of day on the probability of capturing sugar-fed Ae. albopictus. For both sexes, fructose prevalence and content were higher in mosquitoes caught in the morning than in the afternoon. Female Ae. albopictus collected in the residential habitat were significantly more likely to be sugar fed than those collected in the woodland habitat. CONCLUSIONS: These findings provide baseline information about the sugar-feeding patterns of Ae. albopictus and provide essential information to enable an assessment of the potential of ATSBs for vector suppression and control on Masig Island, with relevance to other locations where this species occurs.

12.
Infect Dis Poverty ; 10(1): 123, 2021 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-34627388

RESUMEN

BACKGROUND: Severe dengue is a life-threatening complication; rapid identification of these cases, followed by adequate management is crucial to improve the clinical prognosis. Therefore, this study aimed to identify risk factors and predictors of severe dengue. METHODS: A literature search for studies reporting risk factors of severe dengue among individuals with dengue virus infection was conducted in PubMed, Scopus and Web of Science database from inception to December 31, 2020. Pooled odds ratios (ORs) for patients' demographic characteristics, co-morbidities, and warning signs were estimated using an inverse variance heterogeneity model. RESULTS: We included 143 articles in the meta-analysis from a total of 13 090 articles retrieved from the literature search. The risk factors of severe dengue were: being a child [OR = 1.96; 95% confidence interval (CI): 1.22-3.13], secondary infection (OR = 3.23; 95% CI: 2.28-4.57), and patients with pre-existing diabetes (OR = 2.88; 95% CI: 1.72-4.81) and renal disease (OR = 4.54; 95% CI: 1.55-13.31). Warning signs strongly associated with severe disease were increased haematocrit with a concurrent decrease in platelet count (OR = 5.13; 95% CI: 1.61-16.34), abdominal pain (OR = 2.00; 95% CI: 1.49-2.68), lethargy (OR = 2.73; 95% CI: 1.05-7.10), vomiting (OR = 1.80; 95% CI: 1.43-2.26), hepatomegaly (OR = 5.92; 95% CI: 3.29-10.66), ascites (OR = 6.30; 95% CI: 3.75-10.60), pleural effusion (OR = 5.72; 95% CI: 3.24-10.10) and melena (OR = 4.05; 95% CI: 1.64-10.00). CONCLUSIONS: Our meta-analysis identified children, secondary infection, diabetes and renal disease(s) as important predictors of severe dengue. Our finding also supports the predictive ability of the WHO warning signs to identify severe dengue. These findings are useful for clinicians to identify severe dengue for management and timely interventions.

13.
Braz J Infect Dis ; : 101629, 2021 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-34627783

RESUMEN

BACKGROUND: The recognition of the causal association between Zika virus (ZIKV) infection during pregnancy and congenital abnormalities including microcephaly underlines the importance of preventing this disease in pregnant women (PW) and women of childbearing age (WCA). Although Brazil and other Latin American countries reported a significant reduction in the number of ZIKV infections in recent years, epidemic waves can recur in settings with previous outbreaks as conditions for transmission remain optimal and susceptible populations are continuously replenished. METHODS: In this cross-sectional study, we enrolled 64 PW and 260 non-pregnant WCA attending routine medical appointments in two primary care units in Sao Paulo, Brazil, and assessed knowledge and attitudes about ZIKV infection and prevention. RESULTS: Most women reported knowing that ZIKV is transmitted through the bite of Aedes mosquitos, and most knew that acute symptoms are similar to those seen in Dengue infection. Furthermore, most participants correctly described that ZIKV infection during pregnancy may cause detrimental outcomes for the newborn. However, most ignored that ZIKV infection can be asymptomatic, and only 15% knew about the risk of ZIKV sexual transmission. We found no statistically significant differences between PW and WCA regarding knowledge about ZIKV sexual transmission. Knowledge about ZIKV sexual transmission was significantly associated with education; among participants with ≤12 schooling years, only 9.0% (95%CI 3.4-18.5%) correctly answered that ZIKV can be sexually transmitted, compared to 12.9% (95%CI 8.2-18.8%) among participants with 12-14 schooling years, and to 24.4% (95%CI 15.9-34.9%) of participants with ≥15 schooling years (p = 0.015). Education remained independently associated with knowledge about sexual transmission of ZIKV in a multivariate logistic regression model adjusted for age, race and pregnancy status (p = 0.022). CONCLUSION: Our findings underscore the urgent need of educational and family planning programs that may help prevent detrimental outcomes of ZIKV infection in an endemic area of Brazil.

14.
Cell Host Microbe ; 2021 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-34610295

RESUMEN

Although divergent dengue viruses (DENVs) have been isolated in insects, nonhuman primates, and humans, their relationships to the four canonical serotypes (DENV 1-4) are poorly understood. One virus isolated from a dengue patient, DKE-121, falls between genotype and serotype levels of sequence divergence to DENV-4. To examine its antigenic relationship to DENV-4, we assessed serum neutralizing and protective activity. Whereas DENV-4-immune mouse sera neutralize DKE-121 infection, DKE-121-immune sera inhibit DENV-4 less efficiently. Passive transfer of DENV-4 or DKE-121-immune sera protects mice against homologous, but not heterologous, DENV-4 or DKE-121 challenge. Antigenic cartography suggests that DENV-4 and DKE-121 are related but antigenically distinct. However, DENV-4 vaccination confers protection against DKE-121 in nonhuman primates, and serum from humans immunized with a tetravalent vaccine neutralize DENV-4 and DKE-121 infection equivalently. As divergent DENV strains, such as DKE-121, may meet criteria for serotype distinction, monitoring their capacity to impact dengue disease and vaccine efficacy appears warranted.

15.
PLoS Negl Trop Dis ; 15(10): e0009873, 2021 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-34634046

RESUMEN

A dysregulated or exacerbated inflammatory response is thought to be the key driver of the pathogenesis of severe disease caused by the mosquito-borne dengue virus (DENV). Compounds that restrict virus replication and modulate the inflammatory response could thus serve as promising therapeutics mitigating the disease pathogenesis. We and others have previously shown that macrophages, which are important cellular targets for DENV replication, differentiated in the presence of bioactive vitamin D (VitD3) are less permissive to viral replication, and produce lower levels of pro-inflammatory cytokines. Therefore, we here evaluated the extent and kinetics of innate immune responses of DENV-2 infected monocytes differentiated into macrophages in the presence (D3-MDMs) or absence of VitD3 (MDMs). We found that D3-MDMs expressed lower levels of RIG I, Toll-like receptor (TLR)3, and TLR7, as well as higher levels of SOCS-1 in response to DENV-2 infection. D3-MDMs produced lower levels of reactive oxygen species, related to a lower expression of TLR9. Moreover, although VitD3 treatment did not modulate either the expression of IFN-α or IFN-ß, higher expression of protein kinase R (PKR) and 2'-5'-oligoadenylate synthetase 1 (OAS1) mRNA were found in D3-MDMs. Importantly, the observed effects were independent of reduced infection, highlighting the intrinsic differences between D3-MDMs and MDMs. Taken together, our results suggest that differentiation of MDMs in the presence of VitD3 modulates innate immunity in responses to DENV-2 infection.

16.
Am J Trop Med Hyg ; 2021 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-34634779

RESUMEN

The mosquito Aedes aegypti transmits arboviral diseases at extraordinary rates. Dengue alone afflicts 50 to 100 million people each year, with more than 3 billion at risk globally. This indicates that current approaches to prevention and control are inadequate, and that a paradigm shift from one that largely promotes vertical chemical-based control and vaccine development to one that also concentrates on eliminating the mosquito through actions by the communities it plagues is necessary. We have developed a new social and software platform, DengueChat (denguechat.org), to advance community interventions in arbovirus vector control. It is an interactive platform combining open-source digital communication technologies with face-to-face assemblies. It promotes resident participation in evidence collection, reporting, and analysis, and it incorporates pedagogic information, key messaging, and game concepts to motivate communities to implement vector reduction strategies. Using DengueChat, we conducted a 19-month pilot study in five neighborhoods of Managua, Nicaragua. The results strongly suggest that using the software produced value-added features that enhance community engagement. We measured the entomological and behavioral impacts at different time points and relative risk reduction of entomological indices at the end of the study. The entomological results showed significant risk reductions in disease transmission: Ae. aegypti larvae and pupae indices were reduced by approximately 44% in neighborhoods using DengueChat during one epidemic year, whereas control neighborhoods experienced an increase of more than 500%. A cluster permutation test determined that the probability of household positivity was significantly reduced in neighborhoods that participated in DengueChat compared with the reference neighborhoods (P = 0.0265). Therefore, DengueChat is a promising resource for vector control.

17.
mBio ; : e0253121, 2021 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-34634943

RESUMEN

Insect odorant-binding proteins (OBPs) are small soluble proteins that have been assigned roles in olfaction, but their other potential functions have not been extensively explored. Using CRISPR/Cas9-mediated disruption of Aedes aegypti Obp10 and Obp22, we demonstrate the pleiotropic contribution of these proteins to multiple processes that are essential for vectorial capacity. Mutant mosquitoes have impaired host-seeking and oviposition behavior, reproduction, and arbovirus transmission. Here, we show that Obp22 is linked to the male-determining sex locus (M) on chromosome 1 and is involved in male reproduction, likely by mediating the development of spermatozoa. Although OBP10 and OBP22 are not involved in flavivirus replication, abolition of these proteins significantly reduces transmission of dengue and Zika viruses through a mechanism affecting secretion of viral particles into the saliva. These results extend our current understanding of the role of insect OBPs in insect reproduction and transmission of human pathogens, making them essential determinants of vectorial capacity. IMPORTANCE Aedes aegypti is the major vector for many arthropod-borne viral diseases, such as dengue, Zika, and chikungunya viruses. Previous studies suggested that odorant-binding proteins (OBPs) may have diverse physiological functions beyond the olfactory system in mosquitoes; however, these hypothesized functions have not yet been demonstrated. Here, we have used CRISPR/Cas9-based genome editing to functionally delete (knock out) Obp10 and Obp22 in Aedes aegypti. We showed that disruption of Obp10 or Obp22 significantly impairs female and male reproductive capacity by adversely affecting blood feeding, oviposition, fecundity and fertility, and the development of spermatozoa. We also showed that disruption of Obp10 or Obp22 significantly reduces the transmission of dengue and Zika viruses through a mechanism affecting secretion of viral particles into the saliva. Thus, our study is not only significant in understanding the functions of OBPs in mosquito biology, but also shows that OBPs may represent potent flavivirus transmission-blocking targets. Our study is in this regard particularly timely and important from a translational and public health perspective.

18.
Parasit Vectors ; 14(1): 527, 2021 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-34635176

RESUMEN

The expansion of mosquito-borne diseases such as dengue, yellow fever, and chikungunya in the past 15 years has ignited the need for active surveillance of common and neglected mosquito-borne infectious diseases. The surveillance should be designed to detect diseases and to provide relevant field-based data for developing and implementing effective control measures to prevent outbreaks before significant public health consequences can occur. Mosquitoes are important vectors of human and animal pathogens, and knowledge on their biodiversity and distribution in the Afrotropical region is needed for the development of evidence-based vector control strategies. Following a comprehensive literature search, an inventory of the diversity and distribution of mosquitoes as well as the different mosquito-borne diseases found in Cameroon was made. A total of 290 publications/reports and the mosquito catalogue website were consulted for the review. To date, about 307 species, four subspecies and one putative new species of Culicidae, comprising 60 species and one putative new species of Anopheles, 67 species and two subspecies of Culex, 77 species and one subspecies of Aedes, 31 species and one subspecies of Eretmapodites, two Mansonia, eight Coquillettidia, and 62 species with unknown medical and veterinary importance (Toxorhynchites, Uranotaenia, Mimomyia, Malaya, Hodgesia, Ficalbia, Orthopodomyia, Aedeomyia, and Culiseta and Lutzia) have been collected in Cameroon. Multiple mosquito species implicated in the transmission of pathogens within Anopheles, Culex, Aedes, Eretmapodites, Mansonia, and Coquillettidia have been reported in Cameroon. Furthermore, the presence of 26 human and zoonotic arboviral diseases, one helminthic disease, and two protozoal diseases has been reported. Information on the bionomics, taxonomy, and distribution of mosquito species will be useful for the development of integrated vector management programmes for the surveillance and elimination of mosquito-borne diseases in Cameroon.

19.
Hum Immunol ; 2021 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-34635391

RESUMEN

The recombinant, live, attenuated, tetravalent dengue vaccine CYD-TDV has shown efficacy against all four dengue serotypes. In this exploratory study (CYD59, NCT02827162), we evaluated potential associations of host human leukocyte antigen (HLA) alleles with dengue antibody responses, CYD-TDV vaccine efficacy, and virologically-confirmed dengue (VCD) cases. Children 4-11 years old, who previously completed a phase 2b efficacy study of CYD-TDV in a single center in Thailand, were included in the study. Genotyping of HLA class I and II loci was performed by next-generation sequencing from DNA obtained from 335 saliva samples. Dengue neutralizing antibody titers (NAb) were assessed as a correlate of risk and protection. Regression analyses were used to assess associations between HLA alleles and NAb responses, vaccine efficacy, and dengue outcomes. Month 13 NAb log geometric mean titers (GMTs) were associated with decreased risk of VCD. In the vaccine group, HLA-DRB1*11 was significantly associated with higher NAb log GMT levels (beta: 0.76; p = 0.002, q = 0.13). Additionally, in the absence of vaccination, HLA associations were observed between the presence of DPB1*03:01 and increased NAb log GMT levels (beta: 1.24; p = 0.005, q = 0.17), and between DPB1*05:01 and reduced NAb log GMT levels (beta: -1.1; p = 0.001, q = 0.07). This study suggests associations of HLA alleles with NAb titers in the context of dengue outcomes. This study was registered with clinicaltrials.gov: NCT02827162.

20.
Artículo en Inglés | MEDLINE | ID: mdl-34636011

RESUMEN

Aegle marmelos (L.) Correa belongs to the family Rutaceae is generally known as "bael fruit tree" occuring across the south Asian countries. The current investigation screened the main derivatives from crude ethanolic extracts of the Bael tree leaf and evaluated activity effects on the larvae and adults of Aedes aegypti (L.) Dengue vector mosquito and a non-target aquatic predator. The GC-MS results showed that the peak area was found to be profound in N-methyl-1-adamantaneacetamide (N-M 1a) followed by oleic acid (OA) with 63.08 and 11.43% respectively. The larvicidal activity against the fourth instar larvae and the crude Ex-Am showed prominent mortality rate (93.60%) at the maximum dosage of 100 ppm. The mortality rate of N-M 1a and OA was occurred at 10 ppm (97.73%) and 12 ppm (95.4%). The repellent activity was found to be prominent at crude Ex-Am (50 ppm) as compared to the pure compounds (N-m 1a and OA) with maximum protection time up to 210 min. The non-target screening of Ex-Am, N-M 1a, and OA on mosquito predator Tx. splendens showed that they are scarcely toxic even at the maximum dosage of 1000 ppm (34.13%), 100 ppm (27.3%), and 120 ppm (31.3%) respectively. Thus, the present investigation clearly proved that the crude Ex-Am and their major derivatives Nm 1-a and OA showed their acute larval toxicity as well as potential mosquito repellent against the dengue mosquito and eco-safety against the mosquito predator.

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