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1.
Nat Commun ; 12(1): 1102, 2021 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-33597521

RESUMEN

The four-dengue virus (DENV) serotypes infect several hundred million people annually. For the greatest safety and efficacy, tetravalent DENV vaccines are designed to stimulate balanced protective immunity to all four serotypes. However, this has been difficult to achieve. Clinical trials with a leading vaccine demonstrated that unbalanced replication and immunodominance of one vaccine component over others can lead to low efficacy and vaccine enhanced severe disease. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a live attenuated tetravalent DENV vaccine (TV003), which is currently being tested in phase 3 clinical trials. Here we report, our study to determine if TV003 stimulate balanced and serotype-specific (TS) neutralizing antibody (nAb) responses to each serotype. Serum samples from twenty-one dengue-naive individuals participated under study protocol CIR287 (ClinicalTrials.gov NCT02021968) are analyzed 6 months after vaccination. Most subjects (76%) develop TS nAbs to 3 or 4 DENV serotypes, indicating immunity is induced by each vaccine component. Vaccine-induced TS nAbs map to epitopes known to be targets of nAbs in people infected with wild type DENVs. Following challenge with a partially attenuated strain of DENV2, all 21 subjects are protected from the efficacy endpoints. However, some vaccinated individuals develop post challenge nAb boost, while others mount post-challenge antibody responses that are consistent with sterilizing immunity. TV003 vaccine induced DENV2 TS nAbs are associated with sterilizing immunity. Our results indicate that nAbs to TS epitopes on each serotype may be a better correlate than total levels of nAbs currently used for guiding DENV vaccine development.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Vacunas contra el Dengue/inmunología , Virus del Dengue/inmunología , Dengue/inmunología , Formación de Anticuerpos/inmunología , Especificidad de Anticuerpos/inmunología , Dengue/prevención & control , Dengue/virología , Vacunas contra el Dengue/administración & dosificación , Virus del Dengue/clasificación , Epítopos/inmunología , Humanos , Serotipificación , Especificidad de la Especie , Resultado del Tratamiento , Vacunación/métodos , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología
2.
Science ; 371(6525): 194-200, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33414220

RESUMEN

Medically important flaviviruses cause diverse disease pathologies and collectively are responsible for a major global disease burden. A contributing factor to pathogenesis is secreted flavivirus nonstructural protein 1 (NS1). Despite demonstrated protection by NS1-specific antibodies against lethal flavivirus challenge, the structural and mechanistic basis remains unknown. Here, we present three crystal structures of full-length dengue virus NS1 complexed with a flavivirus-cross-reactive, NS1-specific monoclonal antibody, 2B7, at resolutions between 2.89 and 3.96 angstroms. These structures reveal a protective mechanism by which two domains of NS1 are antagonized simultaneously. The NS1 wing domain mediates cell binding, whereas the ß-ladder triggers downstream events, both of which are required for dengue, Zika, and West Nile virus NS1-mediated endothelial dysfunction. These observations provide a mechanistic explanation for 2B7 protection against NS1-induced pathology and demonstrate the potential of one antibody to treat infections by multiple flaviviruses.


Asunto(s)
Anticuerpos Neutralizantes/química , Anticuerpos Antivirales/química , Virus del Dengue/inmunología , Proteínas no Estructurales Virales/inmunología , Virus del Nilo Occidental/inmunología , Virus Zika/inmunología , Animales , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Reacciones Cruzadas , Cristalografía por Rayos X , Dengue/prevención & control , Dengue/terapia , Endotelio/inmunología , Glicocálix/inmunología , Humanos , Ratones , Conformación Proteica en Lámina beta , Dominios Proteicos , Proteínas no Estructurales Virales/química , Fiebre del Nilo Occidental/prevención & control , Fiebre del Nilo Occidental/terapia , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/terapia
3.
Nat Commun ; 12(1): 151, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33420058

RESUMEN

Mosquito-borne viruses threaten the Caribbean due to the region's tropical climate and seasonal reception of international tourists. Outbreaks of chikungunya and Zika have demonstrated the rapidity with which these viruses can spread. Concurrently, dengue fever cases have climbed over the past decade. Sustainable disease control measures are urgently needed to quell virus transmission and prevent future outbreaks. Here, to improve upon current control methods, we analyze temporal and spatial patterns of chikungunya, Zika, and dengue outbreaks reported in the Dominican Republic between 2012 and 2018. The viruses that cause these outbreaks are transmitted by Aedes mosquitoes, which are sensitive to seasonal climatological variability. We evaluate whether climate and the spatio-temporal dynamics of dengue outbreaks could explain patterns of emerging disease outbreaks. We find that emerging disease outbreaks were robust to the climatological and spatio-temporal constraints defining seasonal dengue outbreak dynamics, indicating that constant surveillance is required to prevent future health crises.


Asunto(s)
Fiebre Chikungunya/epidemiología , Enfermedades Transmisibles Emergentes/epidemiología , Dengue/epidemiología , Brotes de Enfermedades/estadística & datos numéricos , Enfermedades Endémicas/estadística & datos numéricos , Infección por el Virus Zika/epidemiología , Adolescente , Aedes/virología , Animales , Fiebre Chikungunya/prevención & control , Fiebre Chikungunya/transmisión , Fiebre Chikungunya/virología , Virus Chikungunya/aislamiento & purificación , Niño , Preescolar , Enfermedades Transmisibles Emergentes/prevención & control , Enfermedades Transmisibles Emergentes/transmisión , Enfermedades Transmisibles Emergentes/virología , Dengue/prevención & control , Dengue/transmisión , Dengue/virología , Virus del Dengue/aislamiento & purificación , Brotes de Enfermedades/prevención & control , República Dominicana/epidemiología , Enfermedades Endémicas/prevención & control , Monitoreo Epidemiológico , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Control de Mosquitos , Mosquitos Vectores/virología , Análisis Espacio-Temporal , Adulto Joven , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/transmisión , Infección por el Virus Zika/virología
4.
Parasit Vectors ; 14(1): 22, 2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33407778

RESUMEN

BACKGROUND: Due to an increase in mosquito habitats and the lack facilities to carry out basic mosquito control, construction sites in China are more likely to experience secondary dengue fever infection after importation of an initial infection, which may then increase the number of infections in the neighboring communities and the chance of community transmission. The aim of this study was to investigate how to effectively reduce the transmission of dengue fever at construction sites and the neighboring communities. METHODS: The Susceptible-Exposed-Infectious/Asymptomatic-Recovered (SEIAR) model of human and SEI model of mosquitoes were developed to estimate the transmission of dengue virus between humans and mosquitoes within the construction site and within a neighboring community, as well between each of these. With the calibrated model, we further estimated the effectiveness of different intervention scenarios targeting at reducing the transmissibility at different locations (i.e. construction sites and community) with the total attack rate (TAR) and the duration of the outbreak (DO). RESULTS: A total of 102 construction site-related and 131 community-related cases of dengue fever were reported in our area of study. Without intervention, the number of cases related to the construction site and the community rose to 156 (TAR: 31.25%) and 10,796 (TAR: 21.59%), respectively. When the transmission route from mosquitoes to humans in the community was cut off, the number of community cases decreased to a minimum of 33 compared with other simulated scenarios (TAR: 0.068%, DO: 60 days). If the transmission route from infectious mosquitoes in the community and that from the construction site to susceptible people on the site were cut off at the same time, the number of cases on the construction site dropped to a minimum of 74 (TAR: 14.88%, DO: 66 days). CONCLUSIONS: To control the outbreak of dengue fever effectively on both the construction site and in the community, interventions needed to be made both within the community and from the community to the construction site. If interventions only took place within the construction site, the number of cases on the construction site would not be reduced. Also, interventions implemented only within the construction site or between the construction site and the community would not lead to a reduction in the number of cases in the community.


Asunto(s)
Dengue/prevención & control , Dengue/transmisión , Infecciones Asintomáticas/epidemiología , China/epidemiología , Control de Enfermedades Transmisibles , Industria de la Construcción , Dengue/epidemiología , Dengue/virología , Virus del Dengue/fisiología , Brotes de Enfermedades/prevención & control , Susceptibilidad a Enfermedades/epidemiología , Susceptibilidad a Enfermedades/virología , Humanos , Incidencia , Modelos Teóricos , Control de Mosquitos , Mosquitos Vectores/crecimiento & desarrollo , Mosquitos Vectores/virología , Características de la Residencia , Lugar de Trabajo
5.
Science ; 371(6525): 190-194, 2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33414219

RESUMEN

There are no approved flaviviral therapies and the development of vaccines against flaviruses has the potential of being undermined by antibody-dependent enhancement (ADE). The flavivirus nonstructural protein 1 (NS1) is a promising vaccine antigen with low ADE risk but has yet to be explored as a broad-spectrum therapeutic antibody target. Here, we provide the structural basis of NS1 antibody cross-reactivity through cocrystallization of the antibody 1G5.3 with NS1 proteins from dengue and Zika viruses. The 1G5.3 antibody blocks multi-flavivirus NS1-mediated cell permeability in disease-relevant cell lines, and therapeutic application of 1G5.3 reduces viremia and improves survival in dengue, Zika, and West Nile virus murine models. Finally, we demonstrate that 1G5.3 protection is independent of effector function, identifying the 1G5.3 epitope as a key site for broad-spectrum antiviral development.


Asunto(s)
Anticuerpos Neutralizantes/química , Anticuerpos Antivirales/química , Virus del Dengue/inmunología , Proteínas no Estructurales Virales/inmunología , Virus del Nilo Occidental/inmunología , Virus Zika/inmunología , Animales , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/uso terapéutico , Células CHO , Línea Celular , Cricetulus , Reacciones Cruzadas , Dengue/prevención & control , Dengue/terapia , Modelos Animales de Enfermedad , Humanos , Ratones , Dominios Proteicos , Proteínas no Estructurales Virales/química , Viremia/terapia , Fiebre del Nilo Occidental/prevención & control , Fiebre del Nilo Occidental/terapia , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/terapia
9.
J UOEH ; 42(3): 231-236, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32879187

RESUMEN

To reach the target of ending the dengue epidemic by 2030, all effort shall be made to minimize the dengue transmission across the country through effective, efficient, low-cost and sustainable programs. In Indonesia, the evidence of community empowerment on dengue prevention is insufficient. The objective of this study is to explore the opinion of community and larva monitoring workers (Jumantik cadre) on dengue prevention. A structured free listing interview was conducted in April-May 2019 by targeting two groups: the community and larva workers in one village of Sleman, Yogyakarta. Door to door interviews were done until the quota and saturation were reached. Each group was asked four free listing questions. The analysis was performed in these stages: transcribing, coding, combining by the question, and calculating the salience score. The most salient score about vector control in the larva cadre was not hanging up dirty clothes; in the community it was cleaning the bathtub. Both groups cited themself as the salient motivator in joining the vector control. Protecting the environment and keeping healthy were the reasons for participating in the vector control. The larva cadre stated community refusal as the main challenge. The community cited the importance of larva cadre: to monitor the presence of larva. Community empowerment on dengue vector control has not been effortlessly executed at the bottom level.


Asunto(s)
Participación de la Comunidad , Dengue/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Adulto , Dengue/epidemiología , Femenino , Humanos , Indonesia/epidemiología , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Adulto Joven
10.
PLoS Negl Trop Dis ; 14(9): e0008716, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32966283

RESUMEN

The concurrent circulation of dengue and coronavirus disease 2019 (COVID-19) may produce many unfavourable outcomes-such as co-infections; delays in diagnosis, treatment, and mitigation measures; overwhelming of the healthcare system; underreporting of cases; deterioration in surveillance and control interventions; and exacerbation of social inequalities. Indeed, lockdown is greatly compromising the effectiveness of vector control, especially social mobilization campaigns and preventive insecticide spraying in private spaces (indoor and peridomestic spraying). Thus, failure to appropriately implement the full range of vector control interventions can lead to a reduction in their overall effectiveness and an increasing risk of vector-borne diseases circulating. Consequently, the health community and policy makers should develop proactive policies and allocate adequate resources to prevent and manage the resurgence of dengue and other vector-borne diseases in the new era of COVID-19.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Dengue/epidemiología , Dengue/prevención & control , Control de Mosquitos/métodos , Neumonía Viral/epidemiología , Prevención Primaria/métodos , Betacoronavirus , Prestación de Atención de Salud , Humanos , Pandemias , Control de Plagas/métodos , Salud Pública , Tiempo de Tratamiento
11.
PLoS Negl Trop Dis ; 14(9): e0008676, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32956362

RESUMEN

Dengue virus (DENV)-associated disease is a growing threat to public health across the globe. Co-circulating as four different serotypes, DENV poses a unique challenge for vaccine design as immunity to one serotype predisposes a person to severe and potentially lethal disease upon infection from other serotypes. Recent experimental studies suggest that an effective vaccine against DENV should elicit a strong T cell response against all serotypes, which could be achieved by directing T cell responses toward cross-serotypically conserved epitopes while avoiding serotype-specific ones. Here, we used experimentally-determined DENV T cell epitopes and patient-derived DENV sequences to assess the cross-serotypic variability of the epitopes. We reveal a distinct near-binary pattern of epitope conservation across serotypes for a large number of DENV epitopes. Based on the conservation profile, we identify a set of 55 epitopes that are highly conserved in at least 3 serotypes. Most of the highly conserved epitopes lie in functionally important regions of DENV non-structural proteins. By considering the global distribution of human leukocyte antigen (HLA) alleles associated with these DENV epitopes, we identify a potentially robust subset of HLA class I and class II restricted epitopes that can serve as targets for a universal T cell-based vaccine against DENV while covering ~99% of the global population.


Asunto(s)
Reacciones Cruzadas/inmunología , Vacunas contra el Dengue/inmunología , Epítopos de Linfocito T/inmunología , Linfocitos T/inmunología , Dengue/prevención & control , Vacunas contra el Dengue/genética , Virus del Dengue/inmunología , Antígenos HLA/genética , Antígenos HLA/inmunología , Humanos , Modelos Moleculares , Estructura Terciaria de Proteína , Proteoma , Análisis de Secuencia de Proteína , Serogrupo
12.
PLoS Negl Trop Dis ; 14(8): e0008428, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32853197

RESUMEN

Vector-borne diseases are a major cause of morbidity and mortality worldwide. Aedes-borne diseases, in particular, including dengue, chikungunya, yellow fever, and Zika, are increasing at an alarming rate due to urbanisation, population movement, weak vector control programmes, and climate change. The World Health Organization calls for strengthening of vector control programmes in line with the Global Vector Control Response (GVCR) strategy, and many vector control programmes are transitioning to this new approach. The Singapore dengue control programme, situated within the country's larger vision of a clean, green, and sustainable environment for the health and well-being of its citizens, provides an excellent example of the GVCR approach in action. Since establishing vector control operations in the 1960s, the Singapore dengue control programme succeeded in reducing the dengue force of infection 10-fold by the 1990s and has maintained it at low levels ever since. Key to this success is consideration of dengue as an environmental disease, with a strong focus on source reduction and other environmental management methods as the dominant vector control strategy. The programme collaborates closely with other government ministries, as well as town councils, communities, the private sector, and academic and research institutions. Community engagement programmes encourage source reduction, and house-to-house inspections accompanied by a strong legislative framework with monetary penalties help to support compliance. Strong vector and epidemiological surveillance means that routine control activities can be heightened to specifically target dengue clusters. Despite its success, the programme continues to innovate to tackle challenges such as climate change, low herd immunity, and manpower constraints. Initiatives include development of novel vector controls such as Wolbachia-infected males and spatiotemporal models for dengue risk assessment. Lessons learnt from the Singapore programme can be applied to other settings, even those less well-resourced than Singapore, for more effective vector control.


Asunto(s)
Dengue/prevención & control , Control de Mosquitos/métodos , Control de Mosquitos/organización & administración , Aedes/virología , Animales , Participación de la Comunidad , Dengue/epidemiología , Humanos , Mosquitos Vectores/virología , Singapur/epidemiología
13.
Mem Inst Oswaldo Cruz ; 115: e200284, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32785481

RESUMEN

The coronavirus disease of 2019 (COVID-19) pandemic challenges public health systems around the world. Tropical countries will face complex epidemiological scenarios involving the simultaneous transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with viruses transmitted by Aedes aegypti. The occurrence of arboviral diseases with COVID-19 in the Latin America and the Caribbean (LAC) region presents challenges and opportunities for strengthening health services, surveillance and control programs. Financing of training, equipment and reconversion of hospital spaces will have a negative effect on already the limited resource directed to the health sector. The strengthening of the diagnostic infrastructure reappears as an opportunity for the national reference laboratories. Sharing of epidemiological information for the modeling of epidemiological scenarios allows collaboration between health, academic and scientific institutions. The fear of contagion by COVID-19 is constraining people with arboviral diseases to search for care which can lead to an increase in serious cases and could disrupt the operation of vector-control programs due to the reluctance of residents to open their doors to health personnel. Promoting intense community participation along with the incorporation of long lasting innovations in vector control offers new opportunities for control. The COVID-19 pandemic offers challenges and opportunities that must provoke positive behavioral changes and encourage more permanent self-care actions.


Asunto(s)
Aedes/microbiología , Aedes/virología , Infecciones por Coronavirus , Coronavirus , Dengue/prevención & control , Pandemias , Neumonía Viral , Fiebre Amarilla/prevención & control , Américas , Animales , Betacoronavirus , Región del Caribe , Infecciones por Coronavirus/epidemiología , Humanos , Mosquitos Vectores , Neumonía Viral/epidemiología
14.
PLoS Pathog ; 16(8): e1008754, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32776975

RESUMEN

Arbovirus infection of Aedes aegypti salivary glands (SGs) determines transmission. However, there is a dearth of knowledge on SG immunity. Here, we characterized SG immune response to dengue, Zika and chikungunya viruses using high-throughput transcriptomics. We also describe a transcriptomic response associated to apoptosis, blood-feeding and lipid metabolism. The three viruses differentially regulate components of Toll, Immune deficiency (IMD) and c-Jun N- terminal Kinase (JNK) pathways. However, silencing of the Toll and IMD pathway components showed variable effects on SG infection by each virus. In contrast, regulation of the JNK pathway produced consistent responses in both SGs and midgut. Infection by the three viruses increased with depletion of the activator Kayak and decreased with depletion of the negative regulator Puckered. Virus-induced JNK pathway regulates the complement factor, Thioester containing protein-20 (TEP20), and the apoptosis activator, Dronc, in SGs. Individual and co-silencing of these genes demonstrate their antiviral effects and that both may function together. Co-silencing either TEP20 or Dronc with Puckered annihilates JNK pathway antiviral effect. Upon infection in SGs, TEP20 induces antimicrobial peptides (AMPs), while Dronc is required for apoptosis independently of TEP20. In conclusion, we revealed the broad antiviral function of JNK pathway in SGs and showed that it is mediated by a TEP20 complement and Dronc-induced apoptosis response. These results expand our understanding of the immune arsenal that blocks arbovirus transmission.


Asunto(s)
Aedes/inmunología , Apoptosis , Fiebre Chikungunya/inmunología , Proteínas del Sistema Complemento/inmunología , Dengue/inmunología , Sistema de Señalización de MAP Quinasas , Glándulas Salivales/inmunología , Infección por el Virus Zika/inmunología , Aedes/virología , Animales , Fiebre Chikungunya/metabolismo , Fiebre Chikungunya/prevención & control , Fiebre Chikungunya/virología , Virus Chikungunya/inmunología , Proteínas del Sistema Complemento/metabolismo , Dengue/metabolismo , Dengue/prevención & control , Dengue/virología , Virus del Dengue/inmunología , Femenino , Interacciones Huésped-Patógeno , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Insectos Vectores/inmunología , Insectos Vectores/virología , Glándulas Salivales/virología , Transcriptoma , Replicación Viral , Virus Zika/inmunología , Infección por el Virus Zika/metabolismo , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/virología
15.
PLoS Pathog ; 16(7): e1008410, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32726353

RESUMEN

The bacterial endosymbiont Wolbachia is a biocontrol tool that inhibits the ability of the Aedes aegypti mosquito to transmit positive-sense RNA viruses such as dengue and Zika. Growing evidence indicates that when Wolbachia strains wMel or wAlbB are introduced into local mosquito populations, human dengue incidence is reduced. Despite the success of this novel intervention, we still do not fully understand how Wolbachia protects mosquitoes from viral infection. Here, we demonstrate that the Wolbachia strain wPip does not inhibit virus infection in Ae. aegypti. We have leveraged this novel finding, and a panel of Ae. aegypti lines carrying virus-inhibitory (wMel and wAlbB) and non-inhibitory (wPip) strains in a common genetic background, to rigorously test a number of hypotheses about the mechanism of Wolbachia-mediated virus inhibition. We demonstrate that, contrary to previous suggestions, there is no association between a strain's ability to inhibit dengue infection in the mosquito and either its typical density in the midgut or salivary glands, or the degree to which it elevates innate immune response pathways in the mosquito. These findings, and the experimental platform provided by this panel of genetically comparable mosquito lines, clear the way for future investigations to define how Wolbachia prevents Ae. aegypti from transmitting viruses.


Asunto(s)
Aedes/microbiología , Virus del Dengue , Interacciones Microbianas/fisiología , Mosquitos Vectores/microbiología , Wolbachia , Animales , Dengue/prevención & control , Dengue/transmisión , Infecciones por Bacterias Gramnegativas , Control Biológico de Vectores/métodos , Fenotipo
17.
PLoS Negl Trop Dis ; 14(7): e0007278, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32614855

RESUMEN

BACKGROUND: The frequency and magnitude of dengue epidemics has increased dramatically throughout the tropics in the past 40 years due to unplanned urbanization, globalization and lack of effective mosquito control. The commercial capital of Tanzania, Dar es Salaam, is now experiencing regular dengue outbreaks. Three dengue serotypes have been detected in Dar es Salaam (DNV 1, 2 and 3). Without adequate vector monitoring and control, further outbreaks will certainly occur. METHODS/FINDINGS: A case series study followed 97 individuals with confirmed dengue fever (NS1 and/or IgM on rapid diagnostic test and/or PCR positive) to their households in Kinondoni, Dar es Salaam during the 2014 outbreak from a random sample of 202 confirmed cases at Mwananyamala Hospital. Kinondoni wards of Manzese, Mwananyamala, Tandale and Mabibo had the highest number of confirmed cases: 18, 13, 13 and 9 respectively. Individuals were interviewed by questionnaire on dengue prevention practices and houses were inspected for mosquito breeding sites to validate a Habitat Suitability Score (HSS). This is a tool devised to predict the productivity of any potential breeding habitats (PBHs) before the rains begin. There were 12 /312 positive Aedes breeding habitats. Drums/barrels, flowerpots and tyres were the most common breeding habitats. The HSS correctly identified 9/12 of Aedes breeding habitats. Larviciding is already conducted in urban Tanzania for malaria control and the HSS may be a useful means to train individuals on productive Aedes aegypti breeding sites should this program be extended to include dengue control. The population remains poorly informed about dengue transmission and prevention: 22% of respondents said dengue is spread from one person to another and 60% first heard about dengue when already sick. Less than 20% of respondents used personal protection and >80% thought bednets protected against dengue. Mobile phones were owned by almost all individuals followed up and have the potential of being the prime medium for dissemination of information on dengue prevention.


Asunto(s)
Aedes , Dengue/prevención & control , Ecosistema , Conocimientos, Actitudes y Práctica en Salud , Control de Mosquitos , Adolescente , Adulto , Aedes/fisiología , Anciano , Anciano de 80 o más Años , Animales , Cruzamiento , Dengue/epidemiología , Dengue/inmunología , Composición Familiar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tanzanía/epidemiología , Adulto Joven
18.
J Virol ; 94(18)2020 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-32611757

RESUMEN

Dengue virus (DENV) is responsible for the most prevalent and significant arthropod-borne viral infection of humans. The leading DENV vaccines are based on tetravalent live-attenuated virus platforms. In practice, it has been challenging to induce balanced and effective responses to each of the four DENV serotypes because of differences in the replication efficiency and immunogenicity of individual vaccine components. Unlike live vaccines, tetravalent DENV envelope (E) protein subunit vaccines are likely to stimulate balanced immune responses, because immunogenicity is replication independent. However, E protein subunit vaccines have historically performed poorly, in part because the antigens utilized were mainly monomers that did not display quaternary-structure epitopes found on E dimers and higher-order structures that form the viral envelope. In this study, we compared the immunogenicity of DENV2 E homodimers and DENV2 E monomers. The stabilized DENV2 homodimers, but not monomers, were efficiently recognized by virus-specific and flavivirus cross-reactive potently neutralizing antibodies that have been mapped to quaternary-structure epitopes displayed on the viral surface. In mice, the dimers stimulated 3-fold-higher levels of virus-specific neutralizing IgG that recognized epitopes different from those recognized by lower-level neutralizing antibodies induced by monomers. The dimer induced a stronger E domain I (EDI)- and EDII-targeted response, while the monomer antigens stimulated an EDIII epitope response and induced fusion loop epitope antibodies that are known to facilitate antibody-dependent enhancement (ADE). This study shows that DENV E subunit antigens that have been designed to mimic the structural organization of the viral surface are better vaccine antigens than E protein monomers.IMPORTANCE Dengue virus vaccine development is particularly challenging because vaccines have to provide protection against four different dengue virus stereotypes. The leading dengue virus vaccine candidates in clinical testing are all based on live-virus vaccine platforms and struggle to induce balanced immunity. Envelope subunit antigens have the potential to overcome these limitations but have historically performed poorly as vaccine antigens, because the versions tested previously were presented as monomers and not in their natural dimer configuration. This study shows that the authentic presentation of DENV2 E-based subunits has a strong impact on antibody responses, underscoring the importance of mimicking the complex protein structures that are found on DENV particle surfaces when designing subunit vaccines.


Asunto(s)
Anticuerpos Monoclonales/biosíntesis , Anticuerpos Antivirales/biosíntesis , Vacunas contra el Dengue/administración & dosificación , Dengue/prevención & control , Epítopos/inmunología , Vacunación/métodos , Proteínas del Envoltorio Viral/inmunología , Animales , Acrecentamiento Dependiente de Anticuerpo , Chlorocebus aethiops , Reacciones Cruzadas , Dengue/inmunología , Dengue/patología , Dengue/virología , Vacunas contra el Dengue/genética , Vacunas contra el Dengue/inmunología , Virus del Dengue/efectos de los fármacos , Virus del Dengue/genética , Virus del Dengue/inmunología , Modelos Animales de Enfermedad , Epítopos/química , Epítopos/genética , Femenino , Células HEK293 , Humanos , Inmunogenicidad Vacunal , Ratones , Ratones Endogámicos BALB C , Isoformas de Proteínas/administración & dosificación , Isoformas de Proteínas/genética , Isoformas de Proteínas/inmunología , Multimerización de Proteína/efectos de los fármacos , Vacunas de Subunidad , Células Vero , Proteínas del Envoltorio Viral/administración & dosificación , Proteínas del Envoltorio Viral/genética
20.
BMC Public Health ; 20(1): 905, 2020 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-32527239

RESUMEN

BACKGROUND: Controlling sites where mosquitos breed is a key strategy in breaking the cycle of infectious transmission of the dengue virus. Preventive behaviors, such as covering water containers with lids and adding temephos (commercially named Abate sand) in water containers are needed to reduce and control mosquito breeding sites. This study aimed to investigate the impact of dengue-preventive behaviors on Aedes immature production. METHODS: This cross-sectional study used in-person interviews to record occurrence of dengue-preventive behaviors in Bang Kachao, Samut Prakan Province, Thailand. Larval mosquitos in and around houses were observed and recorded, and covered 208 households. RESULTS: It was found that 50% of these households had containers for drinking water and 94% used water containers. Covering water containers with effective lids showed the best success among dengue-preventive behaviors for reducing Aedes immature production. Adding temephos in water containers also was effective. CONCLUSIONS: Such behaviors substantively affected development of Aedes immatures in and around households.


Asunto(s)
Aedes/crecimiento & desarrollo , Dengue/prevención & control , Composición Familiar , Larva/crecimiento & desarrollo , Control de Mosquitos/métodos , Abastecimiento de Agua , Agua , Aedes/virología , Animales , Estudios Transversales , Dengue/virología , Virus del Dengue/crecimiento & desarrollo , Humanos , Larva/virología , Temefós , Tailandia , Agua/química
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