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Background. Most deaths in the 1918 influenza pandemic were caused by secondary bacterial pneumonia. Methods. We performed a systematic review and reanalysis of studies of bacterial vaccine efficacy (VE) in preventing pneumonia an...
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Background. Most deaths in the 1918 influenza pandemic were caused by secondary bacterial pneumonia. Methods. We performed a systematic review and reanalysis of studies of bacterial vaccine efficacy (VE) in preventing pneumonia and mortality among patients with influenza during the 1918 pandemic.
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Although cases of acute cholecystitis, acute pancreatitis, and acute appendicitis following dengue virus infections have been documented, very few large-scale studies have investigated the postdengue risk of these acute abdominal ...
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Although cases of acute cholecystitis, acute pancreatitis, and acute appendicitis following dengue virus infections have been documented, very few large-scale studies have investigated the postdengue risk of these acute abdominal conditions.This retrospective population-based cohort study included all patients with laboratory-confirmed dengue from 2002 to 2015 in Taiwan and 1:4 nondengue individuals matched by age, sex, area of residence, and symptom onset time. Multivariate Cox proportional hazards regression models were used to investigate the short-term (≤ 30 days), medium-term (31–365 days), and long-term (> 1 year) risks of acute cholecystitis, pancreatitis, and appendicitis after dengue infection, adjusted for age, sex, area of residence, urbanization level, monthly income level, and comorbidities. Bonferroni correction was used for multiple testing; E-values were used to assess the robustness of the results to unmeasured confounding.This study included 65,694 individuals with dengue and 262,776 individuals without dengue. Patients with dengue had a significantly increased risk of acute cholecystitis (adjusted hazard ratio (aHR) 60.21; 95% CI 29.11–124.54; P < 0.0001, E-value = 119.92) and acute pancreatitis (aHR 17.13; 95% CI 7.66–38.29; P < 0.0001, E-value = 33.75) within the first 30 days postinfection compared to those without dengue, but this increased risk was not present after that. The incidence rates of acute cholecystitis and pancreatitis in the first 30 days were 18.79 and 5.27 per 10,000, respectively. No increased risk of acute appendicitis was observed among patients with acute dengue infection.This study was the first large epidemiological study to show a significantly increased risk of acute cholecystitis and pancreatitis among patients with dengue during the acute phase of dengue infection, while no such association was observed for acute appendicitis. Early identification of acute cholecystitis and pancreatitis in patients with dengue is crucial for preventing fatal complications.
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ABSTRACT Dengue poses a significant global public health threat, with diverse clinical manifestations due to complex interactions between the host and the pathogen. Recent reports have highlighted elevated serum-free light chain (...
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ABSTRACT Dengue poses a significant global public health threat, with diverse clinical manifestations due to complex interactions between the host and the pathogen. Recent reports have highlighted elevated serum-free light chain (FLC) levels in viral infectious diseases. Hence, our study aimed to investigate serum FLC levels in dengue patients. The findings revealed elevated serum λ FLCs, which were associated with the severity of dengue. Receiver operating characteristic curve (ROC) analysis demonstrated that λ FLCs may serve as a serum marker for identifying dengue disease (AUC: 0.7825, sensitivity: 80, specificity: 71.43) and classifying severe dengue (AUC: 0.8102, sensitivity: 75, specificity: 79.52). The viral protease, Dengue virus (DENV) nonstructural protein 3 (NS3), acts as a protease that cleaves viral polyproteins as well as host substrates. Therefore, we proposed that antibodies might be potential targets of NS3 protease, leading to an increase in FLCs. LC/MS-MS analysis confirmed that λ FLCs were the predominant products after antibody degradation by NS3 protease. Additionally, purified NS3 protease cleaved both human IgG and DENV2-neutralizing antibodies, resulting in the presence of λ FLCs. Moreover, NS3 protease administration in vitro led to a reduction in the neutralizing efficacy of DENV2-neutralizing antibodies. In summary, the elevated serum λ FLC levels effectively differentiate dengue patients from healthy individuals and identify severe dengue. Furthermore, the elevation of serum λ FLCs is, at least in part, mediated through NS3 protease-mediated antibody cleavage. These findings provide new insights for developing diagnostic tools and understanding the pathogenesis of DENV infection.
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The cardinal feature of adaptive immunity is its ability to form memory responses that can be rapidly recalled to contain pathogens upon reencountering. Conferring a robust memory immune response to an infection is a key feature f...
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The cardinal feature of adaptive immunity is its ability to form memory responses that can be rapidly recalled to contain pathogens upon reencountering. Conferring a robust memory immune response to an infection is a key feature for a successful vaccination program. The plasmablasts are cells that not only can secret non-neutralizing antibodies but also can secrete the specific antibodies essential to neutralize and inactivate the invading pathogens. Dengue has been recognized as one of the most important vector-borne human viral diseases globally. Currently, supportive care with vigilant monitoring is the standard practice since there is as yet no approved therapeutic modality to treat dengue. Even though the approved vaccine has become available, its low efficacy with the potential to cause harm is the major hurdle to promote the widespread usage of the vaccine. Despite the decades of research on dengue, the major challenge in dengue vaccine development is the absence of suitable experimental animal models that reflect the pathological features and clinical symptoms, as seen in humans. Dengue is transmitted by the bite of mosquitoes carrying infectious dengue virus (DENV), which has four distinct serotypes. Recently, cases resulting from unconventional transmission routes, such as blood transfusion, organs as well as stem cells and bone marrow transplantations, and mother-to-infant vertical transmission, have been reported, suggesting an alternate route of DENV transmission exists in nature. This review discusses issues and challenges needing to be resolved to develop an effective dengue vaccine. Development of a robust and reliable dengue animal model that can reflect not only dynamic human clinical symptoms but also can answer around why preexisting neutralizing antibodies do not confer protection upon re-infection and immune protection marker for dengue vaccine efficacy evaluation.
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Background Tainan experienced the most severe dengue epidemic in Taiwan in 2015. This study investigates the association between the signs and symptoms at the time of reporting with the adverse dengue prognoses.
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Previous studies suggested that dengue was associated with an increased risk of several autoimmune diseases. However, this association still needs to be explored due to the limitations of these studies. A population-based cohort s...
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Previous studies suggested that dengue was associated with an increased risk of several autoimmune diseases. However, this association still needs to be explored due to the limitations of these studies. A population-based cohort study was conducted using national health databases in Taiwan and included 63,814 newly diagnosed, laboratory-confirmed dengue patients between 2002 and 2015 and 1:4 controls (n = 255,256) matched by age, sex, area of residence and symptom onset time. Multivariate Cox proportional hazard regression models were used to investigate the risk of autoimmune diseases after dengue infection. Dengue patients had a slightly higher risk of overall autoimmune diseases than non-dengue controls (aHR 1.16; P = 0.0002). Stratified analyses by specific autoimmune diseases showed that only autoimmune encephalomyelitis remained statistically significant after Bonferroni correction for multiple testing (aHR 2.72; P < 0.0001). Sixteen (0.025%) dengue patients and no (0%) controls developed autoimmune encephalomyelitis in the first month of follow-up (HR >9999, P < 0.0001), but the risk between groups was not significantly different thereafter. Contrary to previous studies, our findings showed that dengue was associated with an increased short-term risk of a rare complication, autoimmune encephalomyelitis, but not associated with other autoimmune diseases.
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Dengue infection can affect the central nervous system and cause various neurological complications. Previous studies also suggest dengue was associated with a significantly increased long-term risk of dementia. A population-based...
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Dengue infection can affect the central nervous system and cause various neurological complications. Previous studies also suggest dengue was associated with a significantly increased long-term risk of dementia. A population-based cohort study was conducted using national health databases in Taiwan and included 37,928 laboratory-confirmed dengue patients aged ≥ 45 years between 2002 and 2015, along with 151,712 matched nondengue individuals. Subdistribution hazard regression models showed a slightly increased risk of Alzheimer’s disease, and unspecified dementia, non-vascular dementia, and overall dementia in dengue patients than the nondengue group, adjusted for age, sex, area of residence, urbanization level, income, comorbidities, and all-cause clinical visits within one year before the index date. After considering multiple comparisons using Bonferroni correction, only overall dementia and non-vascular dementia remained statistically significant (adjusted SHR 1.13, 95% CI 1.05–1.21, p = 0.0009; E-value 1.51, 95% CI 1.28-NA). Sensitivity analyses in which dementia cases occurring in the first three or five years after the index dates were excluded revealed no association between dengue and dementia. In conclusion, this study found dengue patients had a slightly increased risk of non-vascular dementia and total dementia than those without dengue. However, the small corresponding E-values and sensitivity analyses suggest the association between dengue and dementia may not be causal.
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Background Health advocates and the media often use the rankings of the leading causes of death (CODs) to draw attention to health issues with relatively high mortality burdens in a population. The National Center for Health Stati...
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Background Health advocates and the media often use the rankings of the leading causes of death (CODs) to draw attention to health issues with relatively high mortality burdens in a population. The National Center for Health Statistics (NCHS) publishes “Deaths: leading causes” annually. The ranking list used by the NCHS and statistical offices in several countries includes broad categories such as cancer, heart disease, and accidents. However, the list used by the World Health Organization (WHO) subdivides broad categories (17 for cancer, 8 for heart disease, and 6 for accidents) and classifies Alzheimer disease and related dementias and hypertensive diseases more comprehensively compared to the NCHS list. Regarding the data visualization of the rankings of leading CODs, the bar chart is the most commonly used graph; nevertheless, bar charts may not effectively reveal the changes in the rankings over time. Objective The aim of this study is to use a dashboard with bump charts to visualize the changes in the rankings of the leading CODs in the United States by sex and age from 1999 to 2021, according to 2 lists (NCHS vs WHO). Methods Data on the number of deaths in each category from each list for each year were obtained from the Wide-ranging Online Data for Epidemiologic Research system, maintained by the Center for Disease Control and Prevention. Rankings were based on the absolute number of deaths. The dashboard enables users to filter by list (NCHS or WHO) and demographic characteristics (sex and age) and highlight a particular COD. Results Several CODs that were only on the WHO list, including brain, breast, colon, hematopoietic, lung, pancreas, prostate, and uterus cancer (all classified as cancer on the NCHS list); unintentional transport injury; poisoning; drowning; and falls (all classified as accidents on the NCHS list), were among the 10 leading CODs in several sex and age subgroups. In contrast, several CODs that appeared among the 10 leading CODs according to the NCHS list, such as pneumonia, kidney disease, cirrhosis, and sepsis, were excluded from the 10 leading CODs if the WHO list was used. The rank of Alzheimer disease and related dementias and hypertensive diseases according to the WHO list was higher than their ranks according to the NCHS list. A marked increase in the ranking of unintentional poisoning among men aged 45-64 years was noted from 2008 to 2021. Conclusions A dashboard with bump charts can be used to improve the visualization of the changes in the rankings of leading CODs according to the WHO and NCHS lists as well as demographic characteristics; the visualization can help users make informed decisions regarding the most appropriate ranking list for their needs.
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Background Recent studies have shown that dengue virus (DENV) can efficiently infect bone marrow hematopoietic stem cells (HSCs) as well as the placenta of pregnant women. Although mother-to-infant vertical transmission of DENV th...
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Background Recent studies have shown that dengue virus (DENV) can efficiently infect bone marrow hematopoietic stem cells (HSCs) as well as the placenta of pregnant women. Although mother-to-infant vertical transmission of DENV through the placenta has been well documented, the evidence of cell-associated vertical transmission is still unknown. Whether DENV can infect umbilical cord blood (UCB) cells before reaching the fetus remains to be explored. Here, we proposed that human UCB cells were permissive to the DENV infection and DENV infected CD133+ and CD34+ HSCs are reservoir of the virus that could be reactivated upon re-culturing in suitable cells. Methods Human UCB cells were freshly obtained and subjected to DENV infection. Multicolor flow cytometry (MFCM) was used to demonstrate the phenotypes of the infected HSC populations. Immunofluorescence analysis (IFA) and T-distributed Stochastic Neighbor Embedding (t-SNE) were used to show the association of the DENV antigen, non-structural protein1 (NS1) with HSCs. Key findings UCB cells were highly permissive to DENV infection. DENV altered the phenotype of the infected HSC population, increased the expression of HSCs, and affected the balance of transcription factors (TFs, GATA1/2/3). IFA revealed the association of the DENV antigen, non-structural protein1 (NS1), with CD34+ and CD133+ cells. T-distributed Stochastic Neighbor Embedding (t-SNE) analysis revealed heterogeneity in the distribution of CD133+NS1+, and CD34+ NS1+ cells. DENV particles were recovered from CD133+ and CD34+ cells even when virus production in the supernatant was negligible. Significance We predict that infection of CD133+ and CD34+ cells in the UCB serve as reservoirs for the amplification of DENV in UCB prior to the virus reaching the fetus and facilitate vertical transmission.
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A severe dengue epidemic occurred in 2015 which resulted in over 22,000 laboratory-confirmed cases. A cross-sectional seroprevalence study was conducted during the ending phase of this epidemic to evaluate the true incidence of de...
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A severe dengue epidemic occurred in 2015 which resulted in over 22,000 laboratory-confirmed cases. A cross-sectional seroprevalence study was conducted during the ending phase of this epidemic to evaluate the true incidence of dengue virus (DENV) infection and the level of herd immunity. Adult residents in three administrative districts with high dengue incidence were recruited; workers in two districts with intermediate dengue incidence were also recruited for comparison. DENV-specific IgM and IgG were tested using commercial enzyme-linked immunosorbent assays. DENV RNA was detected using commercial quantitative real-time reverse transcriptase polymerase chain reaction assay. Univariate and multivariate logistic regressions were performed to identify risk factors for recent and past DENV infection. The overall seroprevalence of anti-DENV IgM and IgG in 1391 participants was 6.8 and 17.4%, respectively. The risk of recent DENV infection increased with age, with the elderly having the highest risk of infection. Living in areas with high incidence of reported dengue cases and having family members being diagnosed with dengue in 2015 were also independent risk factors for recent DENV infection. One sample was found to have asymptomatic viremia with viral load as high as 105 PFU/ml. Comparing the seroprevalence of anti-DENV IgM with the incidence of reported dengue cases in 2015, we estimated that 1 out of 3.7 dengue infections were reported to the surveillance system; widespread use of rapid diagnostic tests might contribute to this high reporting rate. The results also indicate that the overall herd immunity remains low and the current approved Dengvaxia? is not quite suitable for vaccination in Taiwan.
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