Factores asociados con malaria y arboviriasis en pacientes con síndrome febril importado: estudio de cohortes retrospectivo / Factors associated with malaria and arboviral disease in patients with imported febrile syndrome: a retrospective cohort study

Objetivos: Definir variables predictoras de malaria y arboviriasis en pacientes que consultan por síndrome febril tras la vuelta de un viaje a zonas tropicales/subtropicales. Método: Estudio de cohortes retrospectivo. Se incluyeron variables demográficas, epidemiológicas, clínicas, analíticas y el diagnóstico final clínico y microbiológico. Se realizó un análisis multivariante y se calcularon los índices de exactitud diagnóstica (sensibilidad, especificidad, valores predictivos) y cocientes de probabilidad de la combinación de dichas variables. Resultados: Se incluyeron 291 pacientes con síndrome febril, 108 tenían malaria (37,1%), 28 arboviriasis (9,6%) y 155 otras causas de fiebre (53,3%). En el análisis multivariante, los pacientes con síndrome febril con más riesgo de padecer malaria fueron los que procedían de África subsahariana [odds ratio ajustado (ORa): 45,85; IC 95%: 9,45-222,49], eran inmigrantes que visitan a familiares y amigos (VFA) (ORa = 3,55; IC 95%: 1,21-10,46), presentaban cifras de plaquetas < 150.000/mm3 (ORa = 16,47; IC 95%: 5,46-49,70) o cefalea (ORa = 10,62; IC 95%: 3,20-35,28). La combinación de estas cuatro variables tiene un cociente de probabilidad positivo (CPP) de 23,72 (IC 95%: 5,76-97,62). Los pacientes con síndrome febril que tienen más riesgo de padecer arboviriasis eran los que procedían de Centroamérica y Sudamérica (OR = 5,07; IC 95%: 1,73-14,92), presentaban exantema (OR = 5,10; IC 95%: 1,72-17,02) o artromialgias (OR = 14,50; IC 95%: 3,05-68,80). La combinación de estas tres variables tiene un CPP de 20,66 (IC 95%: 7,74-55,21). Conclusiones: Los pacientes con síndrome febril que tienen más riesgo de padecer malaria son los que procedían de África subsahariana, eran VFA, presentaban cifras de plaquetas < 150.000/μl o cefalea, y tenían mayor riesgo de padecer arboviriasis si procedían de Centroamérica y Sudamérica, presentaban exantema o artromialgias. (AU)

Objective: To identify predictors of malaria and arboviral disease in patients with febrile syndrome who seek care after traveling from tropical or subtropical locations. Methods: Observational retrospective cohort study. We collected demographic, epidemiologic, and clinical data; laboratory findings; and the clinical and final microbiologic diagnoses. Multivariate analysis was used to calculate indices of diagnostic accuracy (sensitivity, specificity, and predictive values) and coefficients of probability of combinations of variables. Results: Data for 291 patients with febrile syndrome were included; 108 had malaria (37.1%), 28 had an arboviral disease (9.6%), and 155 had other causes of fever (53.3%). Multivariate analysis showed patients most likely to have malaria were those from sub-Saharan Africa, adjusted odds ratio (aOR) of 45.85 (95% CI, 9.45-222.49); immigrants who returned to visit friends and relatives (VFR), aOR of 3.55 (95% CI, 1.21-10.46); or had platelet concentrations <150 000/mm3, aORa of 16.47 (95% CI, 5.46-49.70) or headache, aOR of 10.62 (95% CI, 3.20-35.28). The combination of these 4 variables gave a positive probability coefficient (PPC) of 23.72 (95% CI, 5.76-97.62). Patients with febrile syndrome most likely to have an arboviral disease were those from Central or South America, OR 5.07 (95% CI, 1.73-14.92), and those who had exanthems, OR 5.10 (95% CI, 1.72-17.02) or joint pain, OR 14.50 (95% CI, 3.05-68.80). The combination of these 3 variables gave a PPC of 20.66 (95% CI, 7.74-55.21). Conclusions: Patients with febrile syndrome with the greatest probability of having malaria are those from sub-Saharan Africa, those who are VFR, and those with platelet concentrations under 150.000/μL or headache. Arboviral disease wasmore likely in patients from Central and South America who had exanthems or joint pain. (AU)

Intervenciones educativas para la prevención y control del dengue en adultos: una revisión integrativa / Educational interventions for the prevention and control of dengue in adults: An integrative review

Objetivo: Revisar y sintetizar la producción científica de intervenciones educativas para la prevención y control del dengue en adultos. Método: Revisión integrativa de la literatura, protocolo registrado en INPLASY (202170038). La búsqueda fue realizada en MEDLINE, LILACS, Web of Science y EMBASE, sin fecha de inicio y hasta el 31 de marzo de 2021. Se incluyeron estudios de intervención: ensayos clínicos aleatorizados, estudios clúster y cuasiexperimentales. El desenlace evaluado fue la prevención y el control del dengue. Se realizó la evaluación de la calidad metodológica y del nivel de evidencia de los estudios incluidos. Resultados: Se incluyeron 10 estudios con niveles de evidencia entre 1c a 2dm, correspondiente a países de bajos y medianos ingresos de Asia y América. Se evidenció el uso de ayudas didácticas frente a procesos de educación mediante herramientas digitales y se observó un campo de acción por parte de enfermería desde la educación para la salud. Conclusiones: La educación para la salud en escenarios diferentes a los clínicos puede favorecer el empoderamiento por parte de la población para mejorar las conductas de salud. Por otro lado, la utilización de herramientas electrónicas resulta de gran ayuda para evaluar el efecto de una intervención.(AU)

Objective: To review and synthesize the scientific production of educational interventions for the prevention and control of dengue in adults. Method: Integrative literature review, protocol registered in INPLASY (202170038). The search was performed in MEDLINE, LILACS, Web of Science and EMBASE, with no start date until March 31, 2021. Intervention studies were included: randomized clinical trials, cluster and quasi-experimental studies. The outcome evaluated was dengue prevention and control. The evaluation of the methodological quality and the level of evidence of the included studies was carried out. Results: Ten studies were included with levels of evidence between 1c and 2dm, corresponding to low- and middle-income countries in Asia and America. The use of didactic aids was evidenced against educational processes, digital tools, and a field of action by nursing was observed, from health education. Conclusions: Health education in scenarios other than clinical ones can favor empowerment by the population to improve health behaviors. On the other hand, the use of electronic tools is of great help in evaluating the effect of an intervention.(AU)

The sex pheromone heptacosane enhances the mating competitiveness of sterile Aedes aegypti males.

BACKGROUND: Aedes aegypti is a vector that transmits various viral diseases, including dengue and Zika. The radiation-based sterile insect technique (SIT) has a limited effect on mosquito control because of the difficulty in irradiating males without reducing their mating competitiveness. In this study, the insect sex pheromone heptacosane was applied to Ae. aegypti males to investigate whether it could enhance the mating competitiveness of irradiated males. METHODS: Heptacosane was smeared on the abdomens of Ae. aegypti males that were allowed to mate with untreated virgin females. The insemination rate was used to assess the attractiveness of heptacosane-treated males to females. The pupae were irradiated with different doses of X-rays and γ-rays, and the emergence, survival time, egg number, and hatch rate were detected to find the optimal dose of X-ray and γ-ray radiation. The males irradiated at the optimal dose were smeared with heptacosane, released in different ratios with untreated males, and mated with females. The effect of heptacosane on the mating competitiveness of irradiated mosquitoes was then evaluated by the hatch rate, induced sterility, and mating competitiveness index. RESULTS: Applying heptacosane to Ae. aegypti males significantly increased the insemination rate of females by 20%. Pupal radiation did not affect egg number but significantly reduced survival time and hatch rate. The emergence of the pupae was not affected by X-ray radiation but was affected by γ-ray radiation. Pupae exposed to 60 Gy X-rays and 40 Gy γ-rays were selected for subsequent experiments. After 60 Gy X-ray irradiation or 40 Gy γ-ray irradiation, the average hatch rate was less than 0.1%, and the average survival time was more than 15 days. Moreover, at the same release ratio, the hatch rate of the irradiated group perfumed with heptacosane was lower than that of the group without heptacosane. Conversely, the male sterility and male mating competitiveness index were significantly increased due to the use of heptacosane. CONCLUSIONS: The sex pheromone heptacosane enhanced the interaction between Ae. aegypti males and females. Perfuming males irradiated by X-rays or γ-rays with heptacosane led to a significant increase in mating competitiveness. This study provided a new idea for improving the application effect of SIT.

Evaluating the mosquito host range of Getah virus and the vector competence of selected medically important mosquitoes in Getah virus transmission.

BACKGROUND: The Getah virus (GETV) is a mosquito-borne Alphavirus (family Togaviridae) that is of significant importance in veterinary medicine. It has been associated with major polyarthritis outbreaks in animals, but there are insufficient data on its clinical symptoms in humans. Serological evidence of GETV exposure and the risk of zoonotic transmission makes GETV a potentially medically relevant arbovirus. However, minimal emphasis has been placed on investigating GETV vector transmission, which limits current knowledge of the factors facilitating the spread and outbreaks of GETV. METHODS: To examine the range of the mosquito hosts of GETV, we selected medically important mosquitoes, assessed them in vitro and in vivo and determined their relative competence in virus transmission. The susceptibility and growth kinetics of GETVs in various mosquito-derived cell lines were also determined and quantified using plaque assays. Vector competency assays were also conducted, and quantitative reverse transcription-PCR and plaque assays were used to determine the susceptibility and transmission capacity of each mosquito species evaluated in this study. RESULTS: GETV infection in all of the investigated mosquito cell lines resulted in detectable cytopathic effects. GETV reproduced the fastest in Culex tritaeniorhynchus- and Aedes albopictus-derived cell lines, as evidenced by the highest exponential titers we observed. Regarding viral RNA copy numbers, mosquito susceptibility to infection, spread, and transmission varied significantly between species. The highest vector competency indices for infection, dissemination and transmission were obtained for Cx. tritaeniorhynchus. This is the first study to investigate the ability of Ae. albopictus and Anopheles stephensi to transmit GETV, and the results emphasize the role and capacity of other mosquito species to transmit GETV upon exposure to GETV, in addition to the perceived vectors from which GETV has been isolated in nature. CONCLUSIONS: This study highlights the importance of GETV vector competency studies to determine all possible transmission vectors, especially in endemic regions.

The stability analysis of a co-circulation model for COVID-19, dengue, and zika with nonlinear incidence rates and vaccination strategies.

This paper aims to study the impacts of COVID-19 and dengue vaccinations on the dynamics of zika transmission by developing a vaccination model with the incorporation of saturated incidence rates. Analyses are performed to assess the qualitative behavior of the model. Carrying out bifurcation analysis of the model, it was concluded that co-infection, super-infection and also re-infection with same or different disease could trigger backward bifurcation. Employing well-formulated Lyapunov functions, the model's equilibria are shown to be globally stable for a certain scenario. Moreover, global sensitivity analyses are performed out to assess the impact of dominant parameters that drive each disease's dynamics and its co-infection. Model fitting is performed on the actual data for the state of Amazonas in Brazil. The fittings reveal that our model behaves very well with the data. The significance of saturated incidence rates on the dynamics of three diseases is also highlighted. Based on the numerical investigation of the model, it was observed that increased vaccination efforts against COVID-19 and dengue could positively impact zika dynamics and the co-spread of triple infections.

Insecticidal activity of Simparica and Simparica Trio against Aedes aegypti in dogs.

BACKGROUND: Aedes aegypti is one of the main species responsible for the transmission of mosquito-borne pathogens worldwide. The isoxazoline Sarolaner has excellent efficacy as an acaricide against ticks and mites and as an insecticide against fleas, and potential efficacy against other insects. METHODS: In each of two laboratory studies, 24 dogs were randomly allocated (n = 8/group) to an untreated control group, a Simparica-treated group (at the minimum dose of 2.0 mg/kg sarolaner), or a Simparica Trio-treated group (at the minimum dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel), based on pre-treatment mosquito counts. Treatments were administered orally once on day 0. Each dog was exposed to 50 unfed female adult A. aegypti mosquitoes for 1 h on days 1, 7, 14, 21, 28 and 35. After each exposure, mosquitoes were counted for each dog and characterized as live, moribund or dead, and as fed or unfed. Dead mosquitoes were counted and removed at 12, 24 and 48 h post-exposure in study 1 and at 24, 48, 72, 96 and 120 h post-exposure in study 2. In study 2, mosquito eggs were collected from 72 h post-exposure until 120 h post-exposure. Insecticidal efficacy was calculated based on the reduction of the arithmetic mean live fed-mosquito counts in each of the treated groups versus the untreated control group for every timepoint post-exposure. RESULTS: Adequate challenge was demonstrated in both studies, with arithmetic mean live fed-mosquito counts ranging from 35.5 to 45.0 for the untreated group. Mean mosquito counts for dogs treated with Simparica and Simparica Trio were significantly (P < 0.0001) reduced within 48 h after exposure on all study days. In study 1, Simparica treatment provided ≥ 96.8% reduction in the arithmetic mean live fed-mosquito counts for 28 days, and Simparica Trio treatment provided ≥ 90.3% reduction for 21 days. In study 2, Simparica treatment provided ≥ 99.4% reduction for 35 days (from 48 h onwards), and Simparica Trio treatment provided ≥ 97.8% reduction for 28 days (from 72 h onwards). CONCLUSIONS: Both studies demonstrated that a single oral dose of Simparica or Simparica Trio provides high efficacy against mosquitoes in dogs within 24-72 h after exposure for an entire month.

Chikungunya Outbreak in Country with Multiple Vectorborne Diseases, Djibouti, 2019-2020.

During 2019-2020, a chikungunya outbreak occurred in Djibouti City, Djibouti, while dengue virus and malaria parasites were cocirculating. We used blotting paper to detect arbovirus emergence and confirm that it is a robust method for detecting and monitoring arbovirus outbreaks remotely.

Boletin Epidemiologico Semana 08 (del 19 al 25 de febrero de 2023) / Epidemiological Bulletin Week 08 (from February 19 to 25, 2023)

Resumen de eventos de notificación hasta SE 08/2023. Alertas internacionales. Situación epidemiológica de dengue. Situación epidemiológica de zika y chikungunya. Situación epidemiológica de Infección respiratoria aguda. Situación epidemiológica de Neumonías. Vigilancia centinela de virus respiratorios. Vigilancia centinela de rotavirus. Situación epidemiológica de Enfermedad diarreica aguda

Summary of notification events up to SE 08/2023. International alerts. Epidemiological situation of dengue. Zika and chikungunya epidemiological situation. Epidemiological situation of acute respiratory infection. Epidemiological situation of pneumonias. Sentinel surveillance of respiratory viruses. Rotavirus sentinel surveillance. Epidemiological situation of acute diarrheal disease

[Kawasaki disease cytokine release syndrome and Kawasaki disease shock syndrome: A case report]. / Síndrome de tormenta de citocinas y síndrome de choque por enfermedad de Kawasaki: reporte de un caso.

BACKGROUND: Kawasaki disease is a vasculitis of small and medium vessels, with a high prevalence throughout the world. In addition to coronary aneurysms, this vasculitis can lead to a number of systemic complications, including Kawasaki disease shock syndrome and Kawasaki disease cytokine storm syndrome. CASE REPORT: : Case report: A 12-year-old male patient, who began his condition with heartburn, sudden fever of 40 ºC and jaundice, for which he was prescribed treatment with antipyretics and bismuth subsalicylate, without satisfactory reaction. Gastroalimentary content was added three times, and centripetal maculopapular dermatosis. After 12 hospital stays, he was evaluated by personnel from the Pediatric Immunology service, who reported data on hemodynamic instability due to persistent tachycardia for hours, immediate capillary refill, intense pulse, oliguria of 0.3 mL/kg/h of partial urinary output with condensed urine; the systolic blood pressure figures were below the 50% percentile, and there was polypnea and limit saturation in 93%. In the paraclinical studies, the rapid decrease in platelet count (from 297,000 to 59,000 in 24 hours), as well as a neutrophil-lymphocyte index of 12, drew attention. The concentrations of NS1 size, IgM and IgG for dengue and PCR for SARS virus were determined. -CoV-2, which were negative. The definitive diagnosis of Kawasaki disease was established with Kawasaki disease shock syndrome. The evolution of the patient was satisfactory, with a decrease in fever after the administration of gamma globulin on the tenth day of hospitalization, and a new protocol with prednisone (50 mg/day) was started, when the cytokine storm syndrome due to illness was integrated. Kawasaki syndrome simultaneous with pre-existing disorders, that is, Kawasaki disease and Kawasaki disease shock syndrome due to thrombocytopenia, hepatosplenomegaly, fever, lymphadenopathy; in addition, ferritin of 605 mg/dL and transaminasemia. The control echocardiogram did not show coronary abnormalities and hospital discharge was granted 48 hours after starting treatment with the corticosteroid, with a 14-day follow-up plan. CONCLUSIONS: Kawasaki disease is an autoimmune vasculitis that can worsen with simultaneous syndromes associated with high mortality. It is important to know this type of alterations and their differences to properly discern and implement effective and timely treatment.

INTRODUCCIÓN: La enfermedad de Kawasaki es una vasculitis de pequeños y medianos vasos, con elevada prevalencia en todo el mundo. Además de los aneurismas coronarios, esta vasculitis puede generar diversas complicaciones sistémicas, como el síndrome de choque por enfermedad de Kawasaki y el síndrome de tormenta de citocinas por enfermedad de Kawasaki. REPORTE DE CASO: Paciente masculino de 12 años de edad, que inició su padecimiento con pirosis, fiebre súbita de 40 ºC e ictericia, por lo que se le prescribió tratamiento con antipiréticos y subsalicilato de bismuto, sin reacción satisfactoria. Se agregó vómito de contenido gastroalimentario en tres ocasiones y dermatosis maculopapular centrípeta. Después de 12 horas de estancia intrahospitalaria fue valorado por personal del servicio de Inmunología Pediátrica, quienes informaron datos de inestabilidad hemodinámica por taquicardia persistente, llenado capilar inmediato, pulso intenso, oliguria de 0.3 mL/kg/h de gasto urinario parcial con orina condensada; las cifras de tensión arterial sistólica se encontraban debajo del percentil 50%, y había polipnea y saturación limítrofe en 93%. En los estudios paraclínicos llamó la atención el rápido descenso del conteo plaquetario (de 297,000 a 59,000 en 24 horas), así como el índice neutrófilo-linfocito de 12. Se determinaron las concentraciones de antígeno NS1, IgM e IgG para dengue y PCR para virus SARS-CoV-2, que resultaron negativas. Se estableció el diagnóstico definitivo de enfermedad de Kawasaki con síndrome de choque por enfermedad de Kawasaki. La evolución del paciente fue satisfactoria, con disminución de la fiebre luego de la administración de gammaglobulina en el décimo día de hospitalización, y se inició un nuevo protocolo con prednisona (50 mg/día), al integrarse el síndrome de tormenta de citocinas por enfermedad de Kawasaki simultáneo con las alteraciones preexistentes, es decir: enfermedad de Kawasaki y síndrome de choque por enfermedad de Kawasaki por trombocitopenia, hepatoesplenomegalia, fiebre, adenopatías; además, ferritina de 605 mg/dL y transaminasemia. El ecocardiograma de control no mostró modificaciones coronarias y se otorgó el alta hospitalaria después de 48 horas de iniciar el tratamiento con el corticosteroide, con plan de seguimiento en 14 días. CONCLUSIONES: La enfermedad de Kawasaki es una vasculitis autoinmunitaria que puede agravarse con síndromes simultáneos asociados y generar elevada mortalidad. Es importante conocer este tipo de alteraciones y sus diferencias para discernir de forma adecuada e implementar el tratamiento eficaz y oportuno.

Association of Hematological and Biochemical Parameters with Serological Markers of Acute Dengue Infection during the 2022 Dengue Outbreak in Nepal.

Background: Nepal faced a major dengue outbreak in 2022. The majority of hospitals and laboratories had limited resources for dengue confirmation and had to rely on rapid dengue diagnostic tests. The purpose of the study is to find the predictive hematological and biochemical parameters in each serological phase of dengue infection (NS1 and IgM) that may assist in dengue diagnosis, severity assessment, and patient management via the use of rapid serological tests. Method: A laboratory-based cross-sectional study was conducted among dengue patients. Rapid antigen (NS1) and serological test (IgM/IgG) was performed to diagnose positive dengue cases. Furthermore, hematological and biochemical investigations were carried out and compared between NS1 and/or IgM-positive participants. A logistic regression analysis was used to identify the validity of the hematological and biochemical characteristics for dengue diagnosis as well as patient management. Receiver-operating characteristic (ROC) curve analysis was used to define the best cut-off, sensitivity, and specificity. Result: Multiple logistic regression showed thrombocytopenia (ORA = 1.000; p = 0.006), leukopenia (ORA = 0.999; p < 0.001), glucose level (ORA = 1.028; p = 0.029), aspartate aminotransferase (ORA = 1.131; p = 0.001), and monocytosis (ORA = 2.332; p = 0.020) as significant parameters in the NS1-only positive group. Similarly, thrombocytopenia (ORA = 1.000; p = 0.001), glucose level (ORA = 1.037; p = 0.004), and aspartate aminotransferase (ORA = 1.141; p < 0.001) were significant in IgM-only positive patients. Moreover, thrombocytopenia (ORA = 1.000; p < 0.001), leukopenia (ORA = 0.999; p < 0.001), glucose (ORA = 1.031; p = 0.017), aspartate aminotransferase (ORA = 1.136; p < 0.001), and lymphopenia (ORA = 0.520; p = 0.067) were independent predictors in both NS1 + IgM positive groups. Platelets consistently demonstrated a higher area under the curve with increased sensitivity and specificity throughout all models, while aspartate aminotransferase (AUC = 0.811) and glucose (AUC = 0.712) demonstrated better results when single IgM positivity was observed. The total leukocyte count performed better when both NS1 + IgM were positive (AUC = 0.814). Conclusion: Hence, thrombocytopenia, elevated AST, high glucose level, leukopenia with monocytosis, and leukopenia with lymphopenia may predict dengue diagnosis and its severity during an active infection. Therefore, these laboratory parameters can be used to complement less sensitive rapid tests, improve dengue diagnosis, and help with proper patient management.

S-Adenosyl-l-Homocysteine Exhibits Potential Antiviral Activity Against Dengue Virus Serotype-3 (DENV-3) in Bangladesh: A Viroinformatics-Based Approach.

Dengue outbreak is one of the concerning issues in Bangladesh due to the annual outbreak with the alarming number of death and infection. However, there is no effective antiviral drug available to treat dengue-infected patients. This study evaluated and screened antiviral drug candidates against dengue virus serotype 3 (DENV-3) through viroinformatics-based analyses. Since 2017, DENV-3 has been the predominant serotype in Bangladesh. We selected 3 non-structural proteins of DENV-3, named NS3, NS4A, and NS5, as antiviral targets. Protein modeling and validation were performed with VERIFY-3D, Ramachandran plotting, MolProbity, and PROCHECK. We found 4 drug-like compounds from DRUGBANK that can interact with these non-structural proteins of DENV-3. Then, the ADMET profile of these compounds was determined by admetSAR2, and molecular docking was performed with AutoDock, SWISSDOCK, PatchDock, and FireDock. Furthermore, they were subjected to molecular dynamics (MD) simulation study using the DESMOND module of MAESTRO academic version 2021-4 (force field OPLS_2005) to determine their solution's stability in a predefined body environment. Two drug-like compounds named Guanosine-5'-Triphosphate (DB04137) and S-adenosyl-l-homocysteine (DB01752) were found to have an effective binding with these 3 proteins (binding energy > 33.47 KJ/mole). We found NS5 protein was stable and equilibrated in a 100 ns simulation run along with a negligible (<3Å) root-mean-square fluctuation value. The root-mean-square deviation value of the S-adenosyl-l-homocysteine-NS5 complex was less than 3Å, indicating stable binding between them. The global binding energy of S-adenosyl-l-homocysteine with NS5 was -40.52 KJ/mole as ∆G. Moreover, these 2 compounds mentioned above are non-carcinogenic according to their ADMET (chemical absorption, distribution, metabolism, excretion, and toxicity) profile (in silico). These outcomes suggest the suitability of S-adenosyl-l-homocysteine as a potential drug candidate for dengue drug discovery research.

Virulence network of interacting domains of influenza a and mouse proteins.

There exist several databases that provide virus-host protein interactions. While most provide curated records of interacting virus-host protein pairs, information on the strain-specific virulence factors or protein domains involved, is lacking. Some databases offer incomplete coverage of influenza strains because of the need to sift through vast amounts of literature (including those of major viruses including HIV and Dengue, besides others). None have offered complete, strain specific protein-protein interaction records for the influenza A group of viruses. In this paper, we present a comprehensive network of predicted domain-domain interaction(s) (DDI) between influenza A virus (IAV) and mouse host proteins, that will allow the systematic study of disease factors by taking the virulence information (lethal dose) into account. From a previously published dataset of lethal dose studies of IAV infection in mice, we constructed an interacting domain network of mouse and viral protein domains as nodes with weighted edges. The edges were scored with the Domain Interaction Statistical Potential (DISPOT) to indicate putative DDI. The virulence network can be easily navigated via a web browser, with the associated virulence information (LD50 values) prominently displayed. The network will aid influenza A disease modeling by providing strain-specific virulence levels with interacting protein domains. It can possibly contribute to computational methods for uncovering influenza infection mechanisms mediated through protein domain interactions between viral and host proteins. It is available at https://iav-ppi.onrender.com/home.

Complex network analysis of arboviruses in the same geographic domain: Differences and similarities.

Arbovirus can cause diseases with a broad spectrum from mild to severe and long-lasting symptoms, affecting humans worldwide and therefore considered a public health problem with global and diverse socio-economic impacts. Understanding how they spread within and across different regions is necessary to devise strategies to control and prevent new outbreaks. Complex network approaches have widespread use to get important insights on several phenomena, as the spread of these viruses within a given region. This work uses the motif-synchronization methodology to build time varying complex networks based on data of registered infections caused by Zika, chikungunya, and dengue virus from 2014 to 2020, in 417 cities of the state of Bahia, Brazil. The resulting network sets capture new information on the spread of the diseases that are related to the time delay in the synchronization of the time series among different municipalities. Thus the work adds new and important network-based insights to previous results based on dengue dataset in the period 2001-2016. The most frequent synchronization delay time between time series in different cities, which control the insertion of edges in the networks, ranges 7 to 14 days, a period that is compatible with the time of the individual-mosquito-individual transmission cycle of these diseases. As the used data covers the initial periods of the first Zika and chikungunya outbreaks, our analyses reveal an increasing monotonic dependence between distance among cities and the time delay for synchronization between the corresponding time series. The same behavior was not observed for dengue, first reported in the region back in 1986, either in the previously 2001-2016 based results or in the current work. These results show that, as the number of outbreaks accumulates, different strategies must be adopted to combat the dissemination of arbovirus infections.

Effect of the Tetravalent Dengue Vaccine TAK-003 on Sequential Episodes of Symptomatic Dengue.

In the pivotal phase 3 efficacy trial (NCT02747927) of the TAK-003 dengue vaccine, 5 of 13,380 TAK-003 recipients and 13 of 6,687 placebo recipients experienced two episodes of symptomatic dengue between the first dose and the end of the study, ∼57 months later (patients received the second dose 3 months after the first dose). Two of these participants experienced repeat infection with the same serotype (i.e., homotypic reinfection). In comparison with placebo, the relative risk of a subsequent episode of symptomatic dengue was 0.19 (95% CI, 0.07-0.54) in TAK-003 recipients. Based on the small number of subsequent episodes, these data suggest a potential incremental effect of TAK-003 beyond prevention of the first episode of symptomatic dengue after vaccination.

RNA interference is essential to modulating the pathogenesis of mosquito-borne viruses in the yellow fever mosquito Aedes aegypti.

While it has long been known that the transmission of mosquito-borne viruses depends on the establishment of persistent and nonlethal infections in the invertebrate host, specific roles for the insects' antiviral immune pathways in modulating the pathogenesis of viral infections is the subject of speculation and debate. Here, we show that a loss-of-function mutation in the Aedes aegypti Dicer-2 (Dcr-2) gene renders the insect acutely susceptible to a disease phenotype upon infection with pathogens in multiple virus families associated with important human diseases. Additional interrogation of the disease phenotype demonstrated that the virus-induced pathology is controlled through a canonical RNA interference (RNAi) pathway, which functions as a resistance mechanism. These results suggest comparatively modest contributions of proposed tolerance mechanisms to the fitness of A. aegypti infected with these pathogens. Similarly, the production of virus-derived piwi-interacting RNAs (vpiRNAs) was not sufficient to prevent the pathology associated with viral infections in Dcr-2 null mutants, also suggesting a less critical, or potentially secondary, role for vpiRNAs in antiviral immunity. These findings have important implications for understanding the ecological and evolutionary interactions occurring between A. aegypti and the pathogens they transmit to human and animal hosts.

Bioactivity of brassica seed meals and its compounds as ecofriendly larvicides against mosquitoes.

Strategic, sustainable, and ecofriendly alternatives to chemical pesticides are needed to effectively control mosquitoes and reduce the incidence of their vectored diseases. We evaluated several Brassicaceae (mustard family) seed meals as sources of plant derived isothiocyanates produced from the enzymatic hydrolysis of biologically inactive glucosinolates for the control of Aedes aegypti (L., 1762). Five defatted seed meals (Brassica juncea (L) Czern., 1859, Lepidium sativum L., 1753, Sinapis alba L., 1753, Thlaspi arvense L., 1753, and Thlaspi arvense-heat inactivated and three major chemical products of enzymatic degradation (allyl isothiocyanate, benzyl isothiocyanate and 4-hydroxybenzyl isothiocyanate) were assayed to determine toxicity (LC50) to Ae. aegypti larvae. All seed meals except the heat inactivated T. arvense were toxic to mosquito larvae. L. sativum seed meal was the most toxic treatment to larvae (LC50 = 0.04 g/120 mL dH2O) at the 24-h exposure. At the 72-h evaluation, the LC50 values for B. juncea, S. alba and T. arvense seed meals were 0.05, 0.08 and 0.1 g/120 mL dH2O, respectively. Synthetic benzyl isothiocyanate was more toxic to larvae 24-h post treatment (LC50 = 5.29 ppm) compared with allyl isothiocyanate (LC50 = 19.35 ppm) and 4-hydroxybenzyl isothiocyanate (LC50 = 55.41 ppm). These results were consistent with the higher performance of the benzyl isothiocyanate producing L. sativum seed meal. Isothiocyanates produced from seed meals were more effective than the pure chemical compounds, based on calculated LC50 rates. Using seed meal may provide an effective method of delivery for mosquito control. This is the first report evaluating the efficacy of five Brassicaceae seed meals and their major chemical constituent against mosquito larvae and demonstrates how natural compounds from Brassicaceae seed meals can serve as a promising ecofriendly larvicides to control mosquitoes.

Diagnosis of Dengue Virus Infections Imported to Hungary and Phylogenetic Analysis of Virus Isolates.

BACKGROUND: Dengue virus is one of the most important arbovirus infections of public health concern. Between 2017 and June 2022, 75 imported dengue infections were confirmed by laboratory diagnostic methods in Hungary. Our study aimed to isolate the imported Dengue strains and characterize them by whole-genome sequencing. METHODS: Laboratory diagnosis of imported infections was carried out using both serological and molecular methods. Virus isolation was attempted on Vero E6 cell lines. An in-house amplicon-based whole-genome sequencing method was applied for the detailed molecular characterization of the isolated virus strains. RESULTS: From 75 confirmed Dengue infected patients, 68 samples were used for virus isolation. Isolation and whole-genome sequencing were successful in the case of eleven specimens. Isolated strains belonged to Dengue-1,-2,-3 serotypes. DISCUSSION: The isolated strains corresponded to the circulating genotypes of the visited geographic area, and some of the genotypes were linked with more severe DENV cases in the literature. We found that multiple factors, including viral load, specimen type, and patient antibody status, influence the isolation efficacy. CONCLUSIONS: Analysis of imported DENV strains can help estimate the outcomes of a possible local DENV transmission in Hungary, a threat from the near future.

Effectiveness of Dengue Awareness Calendar on Indigenous Population: Impact on Knowledge, Belief and Practice.

BACKGROUND: Dengue is prevalent among the indigenous community due to impoverished living conditions near the forest fringe areas and lack of health awareness. The study aims to determine the effect of a dengue awareness calendar on knowledge, belief, and practices (KBP) among the indigenous population. METHOD: A cross-sectional study was conducted in nine selected indigenous villages in Selangor, Malaysia. A dengue awareness calendar was distributed to the indigenous communities after pre-intervention. The KBP scores were compared between the pre-and post-intervention. RESULT: A total of 609 paired responses were obtained. Knowledge, perceived severity, cues to action, self-efficacy, and prevention practices were significantly improved after the intervention (p > 0.00). Participants with primary (Odds Ratio (OR) 2.627; 95% CI 1.338-5.160) and secondary level education (OR 2.263; 95% Cl 1.126-4.550) reported a high increment in practices score. High increments in dengue knowledge scores (OR 2.190; 95% CI 1.521-3.757, p < 0.00) were significantly more likely to report a high increment in practices score. Housewives (OR 0.535; 95% Cl 0.289-0.950), perceived severity (OR 0.349; 95% CI 0.184-0.662), and perceived susceptibility (OR 0.474; 95% CI 0.286-0.785) were significantly less likely to report an increment in prevention practices score. CONCLUSION: Findings inferred that the dengue awareness calendar significantly improved knowledge and practices. Our findings revealed the effectiveness of the dengue awareness calendar in dengue prevention among indigenous communities.

Climate change and the displaced person: how vectors and climate are changing the landscape of infectious diseases among displaced and migrant populations.

BACKGROUND: As the climate crisis grows, so does the global burden of displacement. Displacement, whether a direct or indirect consequence of natural disaster, can lead to dire health sequelae. Skin health is no exception to this, with dermatologic disease being a leading concern reported by those who care for displaced persons. Health professionals who provide dermatologic care for displaced persons benefit from understanding how climate change impacts the global profile of infectious agents. METHODS: This review was performed using PubMed and Google Scholar. Search terms included climate change, displaced person, internally displaced person, and refugee, as well as searches of infectious disease dermatology and the specific diseases of interest. Case reports, case series, reviews, and original research articles were included in this review. Non-English studies were not included. RESULTS: In this manuscript several key infectious agents were identified, and we discuss the skin manifestations and impact of climate change on cutaneous leishmaniasis, dengue, chikungunya, zika, malaria, pediculosis, cutaneous larva migrans, cholera, and varicella zoster. CONCLUSIONS: Climate change plays a significant role in the challenges faced by displaced persons, including their skin health. Among the many consequences of climate change is its altering of the ecological profile of infectious agents and vectors that impact displaced persons. Being familiar with this impact can improve dermatologic care for this vulnerable population.