The pathogenesis of dengue in infants is poorly understood. We postulated that dengue severity in infants would be positively associated with markers of viral burden and that maternally derived, ...neutralizing anti-dengue antibody would have decayed before the age at which infants with dengue presented to the hospital. In 75 Vietnamese infants with primary dengue, we found significant heterogeneity in viremia and NS1 antigenemia at hospital presentation, and these factors were independent of disease grade or continuous measures of disease severity. Neutralizing antibody titers, predicted in each infant at the time of their illness, suggested that the majority of infants (65%) experienced dengue hemorrhagic fever when the maternally derived neutralizing antibody titer had declined to <1:20. Collectively, these data have important implications for dengue vaccine research because they suggest that viral burden may not solely explain severe dengue in infants and that neutralizing antibody is a reasonable but not absolute marker of protective immunity in infants.
Dengue hemorrhagic fever can occur in primary dengue virus (DENV) infection of infants. The decay of maternally derived DENV immunoglobulin (Ig) G and the incidence of DENV infection were determined ...in a prospectively studied cohort of 1244 Vietnamese infants. Higher concentrations of total IgG and DENV-reactive IgG were found in cord plasma relative to maternal plasma. Maternally derived DENV-neutralizing and E protein–reactive IgG titers declined to below measurable levels in >90% of infants by 6 months of age. In contrast, IgG reactive with whole DENV virions persisted until 12 months of age in 20% of infants. Serological surveillance identified 10 infants with asymptomatic DENV infection for an incidence of 1.7 cases per 100 person-years. DENV-neutralizing antibodies remained measurable for ⩾1 year after infection. These results suggest that whereas DENV infection in infants is frequently subclinical, there is a window between 4 and 12 months of age where virion-binding but nonneutralizing IgG could facilitate antibody-dependent enhancement
The pathogenesis of severe dengue is not well understood. Maternally derived subneutralizing levels of dengue virus-reactive IgG are postulated to be a critical risk factor for severe dengue during ...infancy. In this study, we found that, in healthy Vietnamese infants, there was a strong temporal association between the Fc-dependent, dengue virus infection-enhancing activity of neat plasma and the age-related epidemiology of severe dengue. We then postulated that disease severity in infants with primary infections would be associated with a robust immune response, possibly as a consequence of higher viral burdens in vivo. Accordingly, in infants hospitalized with acute dengue, the activation phenotype of peripheral-blood NK cells and CD8+ and CD4+ T cells correlated with overall disease severity, but HLA-A*1101-restricted NS3133–142-specific CD8+ T cells were not measurable until early convalescence. Plasma levels of cytokines/chemokines were generally higher in infants with dengue shock syndrome. Collectively, these data support a model of dengue pathogenesis in infants whereby antibody-dependent enhancement of infection explains the age-related case epidemiology and could account for antigen-driven immune activation and its association with disease severity. These results also highlight potential risks in the use of live attenuated dengue vaccines in infants in countries where dengue is endemic.
Hypovolemic shock (dengue shock syndrome (DSS)) is the most common life-threatening complication of dengue. We conducted a genome-wide association study of 2,008 pediatric cases treated for DSS and ...2,018 controls from Vietnam. Replication of the most significantly associated markers was carried out in an independent Vietnamese sample of 1,737 cases and 2,934 controls. SNPs at two loci showed genome-wide significant association with DSS. We identified a susceptibility locus at MICB (major histocompatibility complex (MHC) class I polypeptide-related sequence B), which was within the broad MHC region on chromosome 6 but outside the class I and class II HLA loci (rs3132468, Pmeta = 4.41 × 10−11, per-allele odds ratio (OR) = 1.34 (95% confidence interval: 1.23-1.46)). We identified associated variants within PLCE1 (phospholipase C, epsilon 1) on chromosome 10 (rs3765524, Pmeta = 3.08 × 10−10, per-allele OR = 0.80 (95% confidence interval: 0.75-0.86)). We identify two loci associated with susceptibility to DSS in people with dengue, suggesting possible mechanisms for this severe complication of dengue.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A prospective study of clinical and cytokine profiles of 107 infants with dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) was conducted. Fever, petechiae on the skin, and hepatomegaly were ...the most common clinical findings associated with DHF/DSS in infants. DSS occurred in 20.5% of the patients. Hemoconcentration and thrombocytopenia were observed in 91.5% and 92.5% of the patients, respectively. Serologic testing revealed that almost all of the patients (95.3%) had primary dengue virus infections. These data demonstrate that clinical and laboratory findings of DHF/DSS in infants are compatible with the World Health Organization’s clinical diagnostic criteria for pediatric DHF. The present study is the first to report evidence of production of cytokines in infants with DHF/DSS and to describe the difference between the cytokine profile of infants with primary dengue virus infections and children with secondary infections. Overproduction of both proinflammatory cytokines (interferon-γ and tumor necrosis factor–α) and anti-inflammatory cytokines (interleukin-10 and -6) may play a role in the pathogenesis of DHF/DSS in infants
Understanding trends in dengue disease burden and risk factors for severe disease can inform health service allocation, clinical management, and planning for vaccines and therapeutics. Dengue ...admissions at three tertiary hospitals in Ho Chi Minh City, Vietnam, increased between 1996 and 2009, peaking at 22,860 in 2008. Children aged 6-10 years had highest risk of dengue shock syndrome (DSS); however, mortality was highest in younger children and decreased with increasing age (odds ratio OR = 0.52, 95% confidence interval CI = 0.36-0.75 in 6- to 10- year-old children and OR = 0.27, 95% CI = 0.16-0.44 in 11- to 15-year-old children compared with 1- to 5-year-old children). Males were overrepresented among dengue cases; however, girls had higher risk of DSS (OR = 1.19, 95% CI = 1.14-1.24) and death (OR = 1.57, 95% CI = 1.14-2.17). Young children with dengue had greatest risk of death and should be targeted in dengue vaccine and drug trials. The increased risk of severe outcomes in girls warrants further attention in studies of pathogenesis, health-seeking behavior, and clinical care.
Four deep learning frameworks consisting of Yolov5m and Yolov5m combined with ResNet50, ResNet-101, and EfficientNet-B0, respectively, are proposed for classifying tomato fruit on the vine into three ...categories: ripe, immature, and damaged. For a training dataset consisting of 4500 images and a training process with 200 epochs, a batch size of 128, and an image size of 224 × 224 pixels, the prediction accuracy for ripe and immature tomatoes is found to be 100% when combining Yolo5m with ResNet-101. Meanwhile, the prediction accuracy for damaged tomatoes is 94% when using Yolo5m with the Efficient-B0 model. The ResNet-50, EfficientNet-B0, Yolov5m, and ResNet-101 networks have testing accuracies of 98%, 98%, 97%, and 97%, respectively. Thus, all four frameworks have the potential for tomato fruit classification in automated tomato fruit harvesting applications in agriculture.
BACKGROUND:Understanding viral etiology and age-specific incidence of acute respiratory infections in infants can help identify risk groups and inform vaccine delivery, but community-based data is ...lacking from tropical settings.
METHODS:One thousand four hundred and seventy-eight infants in urban Ho Chi Minh City and 981 infants in a semi-rural district in southern Vietnam were enrolled at birth and followed to 1 year of age. Acute respiratory infection (ARI) episodes were identified through clinic-based illness surveillance, hospital admissions and self-reports. Nasopharyngeal swabs were collected from infants with respiratory symptoms and tested for 14 respiratory pathogens using multiplex reverse transcription-polymerase chain reaction.
RESULTS:Estimated incidence of ARI was 542 and 2691 per 1000 infant-years, and hospitalization rates for ARI were 81 and 138 per 1000 infant-years, in urban and semi-rural cohorts, respectively, from clinic- and hospital-based surveillance. However self-reported ARI episodes were just 1.5-fold higher in the semi-rural versus urban cohort, indicating that part of the urban–rural difference was explained by under-ascertainment in the urban cohort. Incidence was higher in infants ≥6 months of age than <6 months, but this was pathogen-specific. One or more viruses were detected in 53% (urban) and 64% (semi-rural) of samples from outpatients with ARI and in 78% and 66% of samples from hospitalized ARI patients, respectively. The most frequently detected viruses were rhinovirus, respiratory syncytial virus, influenza virus A and bocavirus. ARI-associated hospitalizations were associated with longer stays and more frequent ICU admission than other infections.
CONCLUSIONS:ARI is a significant cause of morbidity in Vietnamese infants and influenza virus A is an under-appreciated cause of vaccine-preventable disease and hospitalizations in this tropical setting. Public health strategies to reduce infant ARI incidence and hospitalization rates are needed.
Infants account for a small proportion of the overall dengue case burden in endemic countries but can be clinically more difficult to manage. The clinical and laboratory features in infants with ...dengue have not been extensively characterised.
This prospective, cross-sectional descriptive study of infants hospitalized with dengue was conducted in Vietnam from November 2004 to December 2007. More than two-thirds of 303 infants enrolled on clinical suspicion of dengue had a serologically confirmed dengue virus (DENV) infection. Almost all were primary dengue infections and 80% of the infants developed DHF/DSS. At the time of presentation and during hospitalization, the clinical signs and symptoms in infants with dengue were difficult to distinguish from those with other febrile illnesses, suggesting that in infants early laboratory confirmation could assist appropriate management. Detection of plasma NS1 antigen was found to be a sensitive marker of acute dengue in infants with primary infection, especially in the first few days of illness.
Collectively, these results provide a systematic description of the clinical features of dengue in infants and highlight the value of NS1 detection for diagnosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights • The diarrhoeal disease burden in a large, prospective infant cohort in Vietnam is defined. • Minimum incidence of clinic-based diarrhoea in infants: 271/1000 infant-years. • Rotavirus ...was most commonly identified, followed by norovirus and bacterial pathogens. • Frequent repeat infections with the same pathogen within 1 year. • Inclusion of rotavirus in the immunization schedule for Vietnam is warranted.
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