Análise da prevalência de internações por dengue no estado do Tocantins entre 2017 e 2022 / The prevalence of hospitalizations and deaths for dengue in the state of Tocantins between 2017 and 2022 / Prevalencia de hospitalizaciones y muertes por dengue en el estado de Tocantins entre 2017 y 2022

O Tocantins é um Estado endêmico para dengue devido aos elevados índices pluviométricos e do saneamento básico escasso. Esta pesquisa objetivou investigar o número de internações por dengue no Estado do Tocantins entre 2017 e 2022. O estudo consiste em um delineamento transversal retrospectivo quantitativo, realizado a partir de dados coletados no Tabnet/DataSUS. Os resultados encontrados foram compilados no programa Microsoft Excel®, e por meio de gráficos e tabelas, foram evidenciados 28.355 casos de dengue confirmados, dos quais apenas 1.798 (6%) necessitaram de hospitalizações, com maior incidência em 2019, tendo Palmas como município mais acometido. Conclui-se, portanto, que a dengue segue sendo uma doença prevalente no Estado, de modo a demandar atenção de gestores de saúde com vistas a reduzir os números altos de casos por meio de vigilância epidemiológica ativa como, também, fornecer o melhor cuidado para os pacientes diagnosticados com dengue, quer seja no âmbito ambulatorial quer no hospitalar.

Tocantins is an endemic state for dengue due to high rainfall rates and poor sanitation. This research aimed to investigate the number of dengue hospitalizations in the State of Tocantins between 2017 and 2022. The study consists of a retrospective quantitative cross-sectional design, performed from data collected in Tabnet/DataSUS. The results found were compiled in Microsoft Excel® program, and by means of graphs and tables, 28,355 confirmed dengue cases were evidenced, of which only 1,798 (6%) required hospitalizations, with a higher incidence in 2019, with Palmas as the most affected municipality. It is concluded, therefore, that dengue remains a prevalent disease in the state, so as to demand attention from health managers with a view to reducing the high numbers of cases through active epidemiological surveillance as well as providing the best care for patients diagnosed with dengue, whether in the outpatient or hospital setting.

Tocantins es un estado endémico para el dengue debido a las altas tasas de precipitación y al saneamiento deficiente. Esta investigación tuvo como objetivo investigar el número de hospitalizaciones por dengue en el Estado de Tocantins entre 2017 y 2022. El estudio consiste en un diseño cuantitativo transversal retrospectivo, realizado a partir de datos recogidos en Tabnet/DataSUS. Los resultados encontrados fueron compilados en el programa Microsoft Excel®, y por medio de gráficos y tablas, se evidenciaron 28.355 casos confirmados de dengue, de los cuales sólo 1.798 (6%) requirieron hospitalizaciones, con mayor incidencia en 2019, siendo Palmas el municipio más afectado. Se concluye, por lo tanto, que el dengue continúa siendo una enfermedad prevalente en el estado, por lo que demanda la atención de los gestores de salud con miras a reducir las altas cifras de casos a través de la vigilancia epidemiológica activa, así como brindar la mejor atención a los pacientes diagnosticados con dengue, ya sea en el ámbito ambulatorio u hospitalario.

RACK1 Associates with RNA-Binding Proteins Vigilin and SERBP1 to Facilitate Dengue Virus Replication.

Dengue virus (DENV) is a mosquito-borne flavivirus responsible for dengue disease, a major human health concern for which no effective treatment is available. DENV relies heavily on the host cellular machinery for productive infection. Here, we show that the scaffold protein RACK1, which is part of the DENV replication complex, mediates infection by binding to the 40S ribosomal subunit. Mass spectrometry analysis of RACK1 partners coupled to an RNA interference screen-identified Vigilin and SERBP1 as DENV host-dependency factors. Both are RNA-binding proteins that interact with the DENV genome. Genetic ablation of Vigilin or SERBP1 rendered cells poorly susceptible to DENV, as well as related flaviviruses, by hampering the translation and replication steps. Finally, we established that a Vigilin or SERBP1 mutant lacking RACK1 binding but still interacting with the viral RNA is unable to mediate DENV infection. We propose that RACK1 recruits Vigilin and SERBP1, linking the DENV genome to the translation machinery for efficient infection. IMPORTANCE We recently identified the scaffolding RACK1 protein as an important host-dependency factor for dengue virus (DENV), a positive-stranded RNA virus responsible for the most prevalent mosquito-borne viral disease worldwide. Here, we have performed the first RACK1 interactome in human cells and identified Vigilin and SERBP1 as DENV host-dependency factors. Both are RNA-binding proteins that interact with the DENV RNA to regulate viral replication. Importantly, Vigilin and SERBP1 interact with RACK1 and the DENV viral RNA (vRNA) to mediate viral replication. Overall, our results suggest that RACK1 acts as a binding platform at the surface of the 40S ribosomal subunit to recruit Vigilin and SERBP1, which may therefore function as linkers between the viral RNA and the translation machinery to facilitate infection.

Manifestaciones oftalmológicas del dengue, el zika y el chikungunya / Ophthalmic manifestations of dengue, zika and chikungunya

Las infecciones por arbovirus constituyen un reto significativo para los sistemas de salud. Cada vez se incrementa el reconocimiento de complicaciones del sistema nervioso central secundarias a ellas, lo que puede ser un dilema para su diagnóstico y tratamiento. Los arbovirus pueden alterar los mecanismos de inmunidad innatos del ojo al dañar las barreras óculo-hemáticas. En esta revisión nos propusimos caracterizar los principales hallazgos oftalmológicos de las enfermedades transmitidas por mosquito, como el dengue, el zika y el chikungunya, y su posible fisiopatología. Se realizó una búsqueda de la literatura sobre el tema en la base de datos de PubMED. En los pacientes con zika y chikungunya se reconocieron frecuentemente la conjuntivitis no purulenta y la queratitis. En los casos de dengue el edema macular y las hemorragias retinianas maculares fueron frecuentes; causaron disminución de la visión y defectos campimétricos; la vasculitis y coriorretinitis periférica podía ser asintomática si la mácula no estaba comprometida. Estuvieron implicados la trombocitopenia y otros procesos fisiopatológicos. En las enfermedades estudiadas se reportaron casos raros con parálisis de nervios oculomotores o neuritis óptica como respuesta autoinmune tardía. Recientemente se reportó el síndrome de zika congénito que incluyó múltiples anomalías del desarrollo. En los neonatos afectados se describió la atrofia macular, así como la pigmentación macular bilateral, la hipoplasia del nervio óptico, la catarata, entre otros. Existen diversas lesiones oculares secundarias a infecciones por dengue, zika y chikungunya que merecen reconocimiento, pues deterioran la función visual temporal o permanentemente(AU)

Arbovirus infections pose a significant challenge to health systems. Awareness of the secondary central nervous system complications caused by these infections is on the increase, which may be a dilemma for their diagnosis and treatment. Arboviruses may alter the innate immunity mechanisms of the eye by damaging blood-retinal barriers. The objective of this review was to characterize the main ophthalmological findings of mosquito-borne diseases, such as dengue, zika and chikungunya, and their possible physiopathology. A bibliographic search about the topic was conducted in the database PubMed. Non-purulent conjunctivitis and keratitis were frequently found in zika and chikungunya patients. Dengue cases often presented macular edema and macular retinal hemorrhage, which caused vision reduction, as well as campimetric defects. Vasculitis and peripheral chorioretinitis could be asymptomatic if the macula was not involved. Thrombocytopenia and other physiopathological processes were also present. Oculomotor nerve palsy and optic neuritis as a late autoimmune response were rarely reported in the diseases studied. Recent reports refer to congenital zika syndrome, which causes multiple developmental abnormalities. Macular atrophy, bilateral macular pigmentation, optic nerve hypoplasia and cataract, among other disorders, were described in affected neonates. A variety of ocular lesions secondary to dengue, zika and chikungunya infection deserve recognition, for they damage visual function either temporarily or permanently(AU)

Dengue y sus manifestaciones atípicas en el departamento de Arauca, Colombia 2010-2015. Revisión de la literatura / Dengue and its atypical manifestations in the department of Arauca, Colombia 2010-2015. Literature review

Objetivo: El propósito de este trabajo ha sido describir las manifestaciones clínicas atípicas del dengue que se han reportado desde una mirada global hasta la situación actual de Colombia, principalmente en el Departamento de Arauca. Método: Se realizó una búsqueda de literatura científica en las bases de datos PubMed y Scielo Public Health, se eligieron los descriptores o palabras relacionadas con la enfermedad y se realizó búsqueda para la descripción de reportes de casos de manifestaciones inusuales producidas por la infección por dengue. Finalmente se buscaron reportes de casos en Colombia por la base de datos SciELO Public Health de manifestaciones atípicas producidas por dengue, así como los reportes del Instituto Nacional de Salud de Colombia. Resultados: De la exploración de 80 revisiones, la búsqueda identificó 26 artículos, se revisaron los resúmenes y se seleccionaron 18 por ajustarse al objetivo de la revisión. Se excluyeron 8 ya que no correspondían directamente a un episodio de complicación directa por dengue. Así mismo de las referencias de los casos reportados en la búsqueda inicial, se tomaron en cuenta para enriquecer el contexto de esta revisión. Conclusiones: Las manifestaciones atípicas resultados de la infección por el virus del dengue, cada vez son más frecuentemente en todo el mundo. Es notorio en esta revisión que la población infantil es blanco de esta infección viral y que la prevención debe estar enfocada a disminuir la transmisión vectorial con el fin de proteger la población en riesgo, además cabe resaltar que las manifestaciones clínicas más prevalentes encontradas fueron las neurológicas y gastrointestinales afectando a la población infantil en su mayoría.(AU)

Objective: The purpose of this work has been to describe the atypical clinical manifestations of dengue that have been reported from a global perspective to the current situation in Colombia, mainly in the Department of Arauca. Method: A scientific literature search was carried out in the PubMed and Scielo Public Health databases, the descriptors or words related to the disease were chosen and a search was carried out for the description of case reports of unusual manifestations produced by dengue infection. Finally, reports of cases in Colombia were searched through the Scielo Public Health database of atypical manifestations produced by dengue, as well as reports from the National Institute of Health of Colombia. Results: From the exploration of 80 reviews, the search identified 26 articles, the abstracts were reviewed, and 18 were selected to fit the purpose of the review. 8 of them were excluded because, they did not correspond directly to an episode of complication from dengue. Likewise, the references of the cases reported in the initial search were taken into account to enrich the context of this review. Conclusions: Atypical manifestations resulting from dengue virus infection are becoming more and more frequent throughout the world. It is well known in this review that the child population is the target of this viral infection and that prevention should be focused on reducing vector transmission in order to protect the population at risk, it should also be noted that the most prevalent clinical manifestations found were neurological and gastrointestinal, affecting the majority of the child population.(AU)

Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2.

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.

Antibody fucosylation predicts disease severity in secondary dengue infection.

Although antiviral antibodies generally confer protective functions, antibodies against dengue virus (DENV) are associated with enhanced disease susceptibility. Antibodies can mediate DENV infection of leukocytes via Fcγ receptors, likely contributing to dengue disease pathogenesis. To determine if this mechanism accounts for variable disease severity, we examined Fab and Fc structures of anti-DENV antibodies from patients before and after infection and with variable disease outcomes. Neither antibody titers nor neutralizing activity correlated with disease severity in DENV-infected populations. Rather, DENV infection induced a specific increase in immunoglobulin G1 (IgG1) afucosylation, and the levels of afucosylated IgG1 were predictive of dengue disease severity. Thus, the IgG1 fucosylation status represents a robust prognostic tool for dengue disease, highlighting the key role of the Fc glycan structure in dengue pathogenesis.

Predictors and Outcomes of Dengue-Associated Acute Kidney Injury.

Dengue viral infections present with a wide clinical spectrum ranging from asymptomatic to severe manifestations with organ involvement. The term "expanded dengue syndrome" has been commonly used to illustrate the unusual or atypical manifestations; acute kidney injury (AKI) is one of the atypical manifestations of this syndrome. The use of heterogeneous criteria to determine the presence of AKI in dengue patients due to the vast diversity in populations led to difficulties in assessing the true incidence of dengue-associated AKI. This review presents a variable, but often high, frequency of dengue-associated AKI among vastly diverse populations with various disease severities. Dengue-associated AKI is not an uncommon complication, and its importance has often been neglected during the management of dengue patients. The risk factors and certain clinical and laboratory findings commonly reported among dengue patients with AKI should be considered to support a timely diagnosis and case management. This review highlights the need for clinicians to be aware of dengue-associated AKI to reduce the morbidity and mortality associated with this common and important tropical disease.

Blood Levels of Galectin-9, an Immuno-Regulating Molecule, Reflect the Severity for the Acute and Chronic Infectious Diseases.

Galectin-9 (Gal-9) is a ß-galactoside-binding lectin capable of promoting or suppressing the progression of infectious diseases. This protein is susceptible to cleavage of its linker-peptides by several proteases, and the resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) and C-terminal CRD, bind to various glycans. It has been suggested that full-length (FL)-Gal-9 and the truncated (Tr)-Gal-9s could exert different functions from one another via their different glycan-binding activities. We propose that FL-Gal-9 regulates the pathogenesis of infectious diseases, including human immunodeficiency virus (HIV) infection, HIV co-infected with opportunistic infection (HIV/OI), dengue, malaria, leptospirosis, and tuberculosis (TB). We also suggest that the blood levels of FL-Gal-9 reflect the severity of dengue, malaria, and HIV/OI, and those of Tr-Gal-9 markedly reflect the severity of HIV/OI. Recently, matrix metallopeptidase-9 (MMP-9) was suggested to be an indicator of respiratory failure from coronavirus disease 2019 (COVID-19) as well as useful for differentiating pulmonary from extrapulmonary TB. The protease cleavage of FL-Gal-9 may lead to uncontrolled hyper-immune activation, including a cytokine storm. In summary, Gal-9 has potential to reflect the disease severity for the acute and chronic infectious diseases.

Distinguishing non severe cases of dengue from COVID-19 in the context of co-epidemics: A cohort study in a SARS-CoV-2 testing center on Reunion island.

BACKGROUND: As coronavirus 2019 (COVID-19) is spreading globally, several countries are handling dengue epidemics. As both infections are deemed to share similarities at presentation, it would be useful to distinguish COVID-19 from dengue in the context of co-epidemics. Hence, we performed a retrospective cohort study to identify predictors of both infections. METHODOLOGY/PRINCIPAL FINDINGS: All the subjects suspected of COVID-19 between March 23 and May 10, 2020, were screened for COVID-19 within the testing center of the University hospital of Saint-Pierre, Reunion island. The screening consisted in a questionnaire surveyed in face-to-face, a nasopharyngeal swab specimen for the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) reverse transcription polymerase chain-reaction and a rapid diagnostic orientation test for dengue. Factors independently associated with COVID-19 or with dengue were sought using multinomial logistic regression models, taking other febrile illnesses (OFIs) as controls. Adjusted Odds ratios (OR) and 95% Confidence Intervals (95%CI) were assessed. Over a two-month study period, we diagnosed 80 COVID-19, 61 non-severe dengue and 872 OFIs cases eligible to multivariate analysis. Among these, we identified delayed presentation (>3 days) since symptom onset (Odds ratio 1.91, 95% confidence interval 1.07-3.39), contact with a COVID-19 positive case (OR 3.81, 95%CI 2.21-6.55) and anosmia (OR 7.80, 95%CI 4.20-14.49) as independent predictors of COVID-19, body ache (OR 6.17, 95%CI 2.69-14.14), headache (OR 5.03, 95%CI 1.88-13.44) and retro-orbital pain (OR 5.55, 95%CI 2.51-12.28) as independent predictors of dengue, while smoking was less likely observed with COVID-19 (OR 0.27, 95%CI 0.09-0.79) and upper respiratory tract infection symptoms were associated with OFIs. CONCLUSIONS/SIGNIFICANCE: Although prone to potential biases, these data suggest that non-severe dengue may be more symptomatic than COVID-19 in a co-epidemic setting with higher dengue attack rates. At clinical presentation, nine basic clinical and epidemiological indicators may help to distinguish COVID-19 or dengue from each other and other febrile illnesses.

Coronavirus disease 2019 and dengue: two case reports.

BACKGROUND: The pandemic of this century has overwhelmed the healthcare systems of affected countries, and all resources have been diverted to coronavirus disease 2019. At the onset, coronavirus disease 2019 can present as any other acute febrile undifferentiated illness. In tropical regions, clinicians are increasingly challenged to differentiate these febrile illnesses without the use of diagnostics. With this pandemic, many of these tropical diseases are neglected and go underreported. Dengue is holoendemic in the Maldives, and dengue viruses circulate throughout the year. Reports about coinfections with dengue virus and severe acute respiratory syndrome coronavirus 2 are scarce, and the outcome and the dynamics of the disease may be altered in the presence of coinfection. We have described the clinical manifestation and serial laboratory profile, and highlighted the atypical findings uncommon in dengue infection. CASE PRESENTATION: Case 1 was a 39-year old Asian male, presented on day 6 of dengue infection with warning signs. Reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 that was done as per hospital protocol was found to be positive. Case 2 was a 38-year old Asian male, was admitted on day 5 of illness with symptoms of acute respiratory infection with positive reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2. Evaluation of progressive leukopenia and thrombocytopenia showed positive dengue serology. CONCLUSION: Clinicians must be conscientious when working on the differential diagnosis of possible tropical diseases in cases of coronavirus disease 2019, specifically, when patients develop hemoconcentration, thrombocytopenia, and transaminitis with elevated expression of aspartate higher than alanine transaminase, which is frequently observed in dengue infection. Caution must be taken during the administration of intravenous fluids when treating patients with coronavirus disease 2019 and dengue coinfection, as coronavirus disease 2019 patients are more prone to develop pulmonary edema. Timely diagnosis and appropriate management are essential to avoid the devastating complications of severe forms of dengue infection. It is important to repeat and reconfirm the dengue serology in coronavirus disease 2019 patients to avoid false positivity. Diligence and care must be taken not to neglect other endemic tropical diseases in the region during the present pandemic.

Effect of IFN-Y +874 T/A polymorphism on clinical manifestations of dengue: a meta-analysis.

Dengue virus (DENV) is a mosquito-borne RNA virus, which infects nearly 3.97 billion people every year in the tropical and subtropical regions of the world. DENV infections can range from unrecognizable illnesses to a spectrum of clinical manifestations such as dengue fever (DF), and more severe and potentially lethal dengue hemorrhagic fever (DHF). The variability of clinical manifestations induced by DENV can be attributed to a variety of extrinsic and intrinsic factors including virulence of the DENV strains and host genetic factors influencing the immune response. Interferon gamma (IFN-Y) is one of the critical immunomodulators implicated in DENV infection, and recent case-control association studies examined the role of +874 T/A polymorphism (rs2430561) of the IFN-Y gene in dengue clinical outcomes. Since the results of the association studies on DENV infection and IFN-Y +874 T/A polymorphism were inconsistent, we performed a meta-analysis to derive a more precise estimate of the association. Searching the databases until 15 March 2020, we identified five studies with a total of 1412 subjects (582 cases and 830 controls), which were included in this meta-analysis. The pooled odds ratio (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Pooled data indicated significant association of the TT genotype with DENV infection (DI), DF, and DHF in the recessive model TT vs AT+AA: OR (DI) = 1.47, 95% CI (1.10-1.97), P = 0.01; OR (DF) = 1.40, 95% CI (1.00-1.94), P = 0.04, OR (DHF) = 1.73, 95% CI (1.05-2.86), P = 0.03, and the genotype contrast TT vs AT: OR (DI) = 1.70, 95% CI (1.18-2.47); P = 0.005, OR (DF) = 1.72, 95% CI (1.12-2.66), P = 0.014, OR (DHF) = 1.76, 95% CI (1.01-3.06), P = 0.046. The genotype contrast AA vs AT showed significant association with the milder form of dengue (DF), OR (DF) = 1.60, 95% CI (1.07-2.41), P = 0.023, but not with the severe form (DHF). Taken together, this meta-analysis indicated that both the homozygous genotypes conferred risk to dengue, albeit with varied clinical outcomes, and revealed a protective role of the heterozygous genotype against DENV infection.

18F-fluorodeoxyglucose positron emission tomography as a window into human dengue pathophysiology.

In mouse models of dengue virus (DENV) infection, 18F-FDG PET is able to sensitively detect tissue-specific sites of inflammation and disease activity, as well as track therapeutic response to anti- DENV agents. However, the use of 18F-FDG PET to study the pathogenesis of inflammation and disease activity in DENV infection in humans, has not been clinically validated. Here we report the 18F-FDG PET imaging results of two patients during the febrile phase of acute DENV infection, paired with serial serum viral load, NS1 and proinflammatory cytokine measurements. Our findings demonstrate that 18F-FDG PET is able to sensitively detect and quantify organ-specific inflammation in the lymph nodes and spleen, in classic acute dengue fever. This raises the potential for 18F-FDG PET to be used as a research tool that may provide further insights into disease pathogenesis.

Atypical neurological manifestations of dengue fever: a case series and mini review.

BACKGROUND: In this mini review, we discuss some of the atypical neurological manifestations of dengue virus and attempt to bring them to attention to highlight the neurotropic property of the dengue virus. METHODS: Cases were chosen from retrospective hospital and outpatient records of all patients seropositive for dengue who attended the neurology referral. Seven patients have been chosen as illustrative examples of dengue-associated neurological involvement. We discuss the various central and peripheral nervous system involvement of patients and discuss the relevant findings in them. CONCLUSION: Through this case series, we wish to highlight that the dengue virus can affect the nervous system at various targets, using multiple mechanisms of pathogenesis to generate a plethora of presentations. Hence, it is vital to be aware of its presentations to be able to diagnose dengue and treat it accordingly.

Impact of Nutritional Status on the Severity of Dengue Infection Among Pediatric Patients in Southern Thailand.

BACKGROUND: Given the lack of specific antiviral drugs and effective vaccine for dengue infection, factors such as host nutritional status that may alter disease progression require investigation. This study examined the relationship between baseline nutritional status and severity of dengue infection in pediatric patients. METHODS: Data from dengue patients 1-14 years of age treated at four hospitals in southern Thailand (2017-2018) were reviewed. Dengue infection was classified as dengue fever, dengue hemorrhagic fever and dengue shock syndrome. Children's nutritional status was assessed based on international and national growth charts. Binary logistic regression was used to identify factors associated with dengue severity and malnutrition. RESULTS: Overall, 248, 281 and 43 patients had dengue fever, dengue hemorrhagic fever and dengue shock syndrome, respectively. Overweight was associated with increased risk of dengue severity [odds ratio (OR) = 1.76, 95% confidence interval (CI): 1.13-2.75, P = 0.012; OR = 1.84, 95% CI: 1.09-3.09, P = 0.022, per international and national growth criteria, respectively). Stunting was associated with decreased risk of dengue severity (OR = 0.54, 95% CI: 0.33-0.88, P = 0.013; OR = 0.61, 95% CI: 0.39-0.95, P = 0.030, per international and national growth criteria, respectively). Being overweight was significantly and positively associated with levels of hemoglobin >14 g/dL, hematocrit >42%, hemoconcentration ≥20% and platelet count ≤50,000/mm, whereas being stunted was significantly and negatively associated with levels of hemoglobin >14 g/dL and hematocrit >42%. CONCLUSIONS: These findings support a hypothesis that malnutrition might influence the severity of dengue infection through host immune response. Overweight children with dengue infections should be closely observed for early signs of severe dengue infection.

Crocetin Improves Dengue Virus-Induced Liver Injury.

Dengue virus (DENV) infection is one of the most widespread mosquito-borne viral infections. Liver injury is commonly observed in severe DENV infection, and the present study aimed to examine the efficacy of crocetin treatment in an immunocompetent mouse model of DENV infection exhibiting liver injury. The efficacy of crocetin treatment in DENV-induced liver injury was assessed via both transaminase levels and histopathology analysis. A real-time polymerase chain reaction array was then used to describe the expression of 84 apoptosis-related genes. Using real-time RT-PCR and Western blot analysis, the gene expressions of host factors were investigated. Additionally, the effect of crocetin in NF-kB signaling during DENV infection was studied. We did not observe any significant reduction in virus production when DENV-infected mice were treated with crocetin. However, DENV-infected mice treated with crocetin showed reduced DENV-induced apoptosis. The real-time polymerase chain reaction array revealed pro-inflammatory cytokine expressions to be significantly reduced in the crocetin-treated DENV-infected mice. We also found that crocetin could effectively modulate antioxidant status in DENV-infected mice. Moreover, crocetin demonstrated the ability to reduce the nuclear translocation of NF-kB in DENV-infected mice. Our results suggest that crocetin treatment does not inhibit DENV replication in the liver of DENV-infected mice; however, we did find that crocetin improves host responses that reduce liver injury.

Nutritional status impacts dengue virus infection in mice.

BACKGROUND: Dengue virus (DENV) is estimated to infect 390 million people annually. However, few host factors that alter disease severity are known. Malnutrition, defined as both over- and undernutrition, is a growing problem worldwide and has long been linked to dengue disease severity by epidemiological and anecdotal observations. Accordingly, we sought to establish a mouse model to assess the impact of nutritional status on DENV disease severity. RESULTS: Using transiently immunocompromised mice, we established a model of mild dengue disease with measurable viremia. We then applied it to study the effects of healthy weight, obese, and low-protein diets representing normal, over-, and undernutrition, respectively. Upon infection with DENV serotype 2, obese mice experienced more severe morbidity in the form of weight loss and thrombocytopenia compared to healthy weight groups. Additionally, obesity altered cytokine expression following DENV infection. Although low protein-fed mice did not lose significant weight after DENV2 infection, they also experienced a reduction in platelets as well as increased spleen pathology and viral titers. CONCLUSIONS: Our results indicate that obese or undernourished mice incur greater disease severity after DENV infection. These studies establish a role for nutritional status in DENV disease severity.

Vaso-occlusive crisis in a sickle cell patient after transfusion-transmitted dengue infection.

CASE REPORT: A 26-year-old woman with sickle cell disease (SCD) on chronic transfusion therapy complained of severe arthralgia, myalgia, abdominal pain, headache, and fever 24 hours after transfusion of a red blood cells (RBCs). Dengue virus (DENV) infection was suspected and the patient was hospitalized for clinical support and RBC transfusion, to lower the hemoglobin S to less than 30%. The patient's clinical condition improved approximately 8 days after the onset of symptoms. RESULTS: DENV type 2 (DENV-2) TaqMan real-time polymerase chain reaction was negative in the patient's pretransfusion sample while the posttransfusion sample was positive (Ct, 27.8), suggesting a high viral load and an acute infection. To investigate DENV transfusion transmission (TT-DENV) the stored donor serum was tested and was also positive (Ct, 25.8). Molecular typing confirmed the presence of DENV-2. The phylogenetic analysis of the DENV-2 strains obtained from both donor and patient samples were classified as the Southeast Asia-American genotype (Genotype III) and demonstrated 100% genomic identity, indicating TT-DENV. CONCLUSION: This is the first description of TT-DENV in a SCD patient. A presumed high viral load in the transfused RBC unit probably determined the early clinical manifestation. In endemic regions dengue fever should be considered as differential diagnosis in SCD patients with fever and acute pain crisis, mainly during DENV outbreaks.

Blood pressure trend in hospitalized adult dengue patients.

BACKGROUND: Monitoring of blood pressure is an important part of management of dengue illness. Large scale studies of temporal trend of blood pressure in adult dengue are lacking. In this study, we examined the differences in time trend of systolic (SBP) and diastolic blood pressure (DBP) in patients with and without severe dengue (SD), dengue hemorrhagic fever (DHF) and pre-existing hypertension, and elderly versus non-elderly patients. METHODS: We studied a retrospective cohort from 2005 to 2008 of 6,070 hospitalized adult dengue patients confirmed by polymerase chain reaction or clinical criteria plus positive dengue serology. Dengue severity was defined according to World Health Organization 1997 and 2009 guidelines. We used Bayesian hierarchical Markov models to compare the daily mean SBP and DBP between different subgroups. Analysis was conducted by day of defervescence (denoted as day 0), and day of illness onset (denoted as day 1) respectively. RESULTS: SBP decreased to a nadir during the critical phase before defervescence and was significantly lower for patients with SD or DHF, compared with patients without SD or DHF. DBP increased marginally more for patients with SD or DHF in the critical phase before defervescence. By day of defervescence, comparison of patients with and without SD showed significant difference in SBP from day -6 to day +6, except days +1, +3 and +5, and similarly in DBP except days 0, and +4 to +6. Comparison of patients with and without DHF showed significant difference in SBP from day -6 to day -1, but for DBP, significant difference was noted from day -6 to day +6, except day -2 to day 0. By day of illness, SBP differed significantly between patients with and without SD from illness days 1 to 10, and DBP from illness days 7 to 12. Between patients with and without DHF, SBP differed significantly on illness days 1, 2, 4 to 7, while DBP from days 7 to 12. On analysis by days of defervescence or by days of illness, elderly patients and those with hypertension showed consistently higher SBP and DBP throughout their hospitalization, as compared with their younger and non-hypertensive counterparts. CONCLUSION: In SD or DHF, SBP decreased to a nadir around the day of defervescence, and recovered to a level exceeding that in febrile phase by days 2 or 3 post-defervescence. Elderly patients and patients with pre-existing hypertension maintained higher SBP and DBP throughout the duration of dengue infection.

Case report: An unusual presentation of acute promyelocytic leukemia in a middle aged female mimicking dengue infection.

RATIONALE: Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myeloid leukemia (AML). M3v phenotype is a less common presentation of APL and these patients usually present with leukocytosis and abnormal promyelocytes that are characterized by sparse granulation and are less likely to have faggot cells with multiple Auer rods. Distinguishing M3v phenotype from acute febrile illness can be challenging as the diagnosis relies on examination of peripheral smear. PATIENT CONCERNS: Fifty-seven-year-old female who presented after recent trip to Dominican Republic for high grade fever and gum bleeding. She was exposed to patients with Dengue fever during her stay. At presentation, patient had leukocytosis, thrombocytopenia, and urinalysis showing bacteria and white cell. She was started on treatment for urinary tract infection. Patient remained febrile and thrombocytopenia worsened. On day 2, flow cytometry of the peripheral smear showed 43% medium sized blasts. Fluorescence in situ hybridization was positive for promyelocytic leukemia/retinoic acid receptor alpha. DIAGNOSES: The patient was diagnosed with APL. INTERVENTIONS: Patient was started on treatment with all-trans retinoic acid and arsenic trioxide along with supportive care OUTCOMES:: Patient had a favorable clinical response and her symptoms subsided. LESSONS: Flow cytometry of the peripheral smear is key to diagnosis of suspected APL. One must maintain high suspicion for this life-threatening condition as early diagnosis saves lives.