It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that ...cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection.
49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001), 28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized following recovery. B cell counts were not significantly associated with severity. CD8 activation peaked 6-8 days after mild influenza onset, when 13% (6-22%) were HLADR+CD38+, and was accompanied by a significant loss of resting/CD27+CD28+ cells without accumulation of CD27+CD28- or CD27-CD28- cells. In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was excessive (30-90% HLADR+CD38+) in association with accumulation of CD27+CD28- cells and maintenance of CD8 counts.
Severe influenza is associated with transient T and NK cell deficiency. CD8 phenotype changes during mild influenza are consistent with a rapidly resolving memory response whereas in severe influenza activation is either delayed or excessive, and partially differentiated cells accumulate within blood indicating that recruitment of effector cells to the lung could be impaired.
Klebsiella pneumoniae is now recognized as an urgent threat to human health because of the emergence of multidrug-resistant strains associated with hospital outbreaks and hypervirulent strains ...associated with severe community-acquired infections. K. pneumoniae is ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure of K. pneumoniae, so it is difficult to recognize or understand the emergence of clinically important clones within this highly genetically diverse species. Here we present a detailed genomic framework for K. pneumoniae based on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting of K. pneumoniae into three distinct species, KpI (K. pneumoniae), KpII (K. quasipneumoniae), and KpIII (K. variicola). Further, for K. pneumoniae (KpI), the entity most frequently associated with human infection, we show the existence of >150 deeply branching lineages including numerous multidrug-resistant or hypervirulent clones. We show K. pneumoniae has a large accessory genome approaching 30,000 protein-coding genes, including a number of virulence functions that are significantly associated with invasive community-acquired disease in humans. In our dataset, antimicrobial resistance genes were common among human carriage isolates and hospital-acquired infections, which generally lacked the genes associated with invasive disease. The convergence of virulence and resistance genes potentially could lead to the emergence of untreatable invasive K. pneumoniae infections; our data provide the whole-genome framework against which to track the emergence of such threats.
Scrub typhus has been documented since 1932 in Vietnam, however, the disease burden of scrub typhus remains poorly understood in the country. We conducted this study to describe the phylogenetic ...analysis of the 56-kDa type-specific antigen (TSA) gene of Orientia tsutsugamushi associated with PCR positive cases of scrub typhus. Of 116 positive samples, 65 type-specific antigen gene sequences were obtained and classified into 3 genogroups: Karp, Kato and Gilliam. The Karp genogroup was the most frequently detected phylogenetic cluster in the study with 30 samples (46%), followed by Kato and Gilliam with 20 (31%) and 15 (23%), respectively. All sequences showed 94-100% nucleotide similarity to reference sequences collected in the central part of Vietnam in 2017. Patients infected with Karp genogroup were more likely to have significant thrombocytopenia than the other genogroups. These results suggest that any scrub typhus vaccine considered for use in Vietnam should provide protection against each of these 3 genogroups.
The selective expression of CD137 on cells of the immune system (e.g., T and DC cells) and oncogenic cells in several types of cancer leads this molecule to be an attractive target to discover cancer ...immunotherapy. Therefore, specific antibodies against CD137 are being studied and developed aiming to activate and enhance anti-cancer immune responses as well as suppress oncogenic cells. Accumulating evidence suggests that anti-CD137 antibodies can be used separately to prevent tumor in some cases, while in other cases, these antibodies need to be co-administered with other antibodies or drugs/vaccines/regents for a better performance. Thus, in this work, we aim to update and discuss current knowledge about anti-cancer effects of anti-CD137 antibodies as mono- and combined-immunotherapies.
Abstract
Background
An endotracheal tube cuff pressure between 20 and 30 cmH2O is recommended to prevent ventilator-associated respiratory infection (VARI). We aimed to evaluate whether continuous ...cuff pressure control (CPC) was associated with reduced VARI incidence compared with intermittent CPC.
Methods
We conducted a multicenter open-label randomized controlled trial in intensive care unit (ICU) patients within 24 hours of intubation in Vietnam. Patients were randomly assigned 1:1 to receive either continuous CPC using an automated electronic device or intermittent CPC using a manually hand-held manometer. The primary endpoint was the occurrence of VARI, evaluated by an independent reviewer blinded to the CPC allocation.
Results
We randomized 600 patients; 597 received the intervention or control and were included in the intention to treat analysis. Compared with intermittent CPC, continuous CPC did not reduce the proportion of patients with at least one episode of VARI (74/296 25% vs 69/301 23%; odds ratio OR 1.13; 95% confidence interval CI .77–1.67. There were no significant differences between continuous and intermittent CPC concerning the proportion of microbiologically confirmed VARI (OR 1.40; 95% CI .94–2.10), the proportion of intubated days without antimicrobials (relative proportion RP 0.99; 95% CI .87–1.12), rate of ICU discharge (cause-specific hazard ratio HR 0.95; 95% CI .78–1.16), cost of ICU stay (difference in transformed mean DTM 0.02; 95% CI −.05 to .08, cost of ICU antimicrobials (DTM 0.02; 95% CI −.25 to .28), cost of hospital stay (DTM 0.02; 95% CI −.04 to .08), and ICU mortality risk (OR 0.96; 95% CI .67–1.38).
Conclusions
Maintaining CPC through an automated electronic device did not reduce VARI incidence.
Clinical Trial Registration
NCT02966392.
The results of this randomised controlled trial demonstrate that continuous endotracheal cuff pressure control using an electronic automated device does not reduce the occurrence of ventilator-associated respiratory infection (VARI) in intubated patients compared with intermittent control.
Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent ...variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening.
Community acquired bloodstream infection (CABSI) in low- and middle income countries is associated with a high mortality. This study describes the clinical manifestations, laboratory findings and ...correlation of SOFA and qSOFA with mortality in patients with CABSI in northern Vietnam.
This was a retrospective study of 393 patients with at least one positive blood culture with not more than one bacterium taken within 48 h of hospitalisation. Clinical characteristic and laboratory results from the first 24 h in hospital were collected. SOFA and qSOFA scores were calculated and their validity in this setting was evaluated.
Among 393 patients with bacterial CABSI, approximately 80% (307/393) of patients had dysfunction of one or more organ on admission to the study hospital with the most common being that of coagulation (57.1% or 226/393). SOFA performed well in prediction of mortality in those patients initially admitted to the critical care unit (AUC 0.858, 95%CI 0.793-0.922) but poor in those admitted to medical wards (AUC 0.667, 95%CI 0.577-0.758). In contrast qSOFA had poor predictive validity in both settings (AUC 0.692, 95%CI 0.605-0.780 and AUC 0.527, 95%CI 0.424-0.630, respectively). The overall case fatality rate was 28%. HIV infection (HR = 3.145, p = 0.001), neutropenia (HR = 2.442, p = 0.002), SOFA score 1-point increment (HR = 1.19, p < 0.001) and infection with Enterobacteriaceae (HR = 1.722, p = 0.037) were independent risk factors for in-hospital mortality.
Organ dysfunction was common among Vietnamese patients with CABSI and associated with high case fatality. SOFA and qSOFA both need to be further validated in this setting.
Trichinellosis in Vietnam Van De, Nguyen; Thi Nga, Vu; Dorny, Pierre ...
The American journal of tropical medicine and hygiene,
06/2015, Volume:
92, Issue:
6
Journal Article
Peer reviewed
Open access
Trichinellosis is a zoonotic parasitic disease with a worldwide distribution. The aim of this work was to describe the epidemiological and clinical data of five outbreaks of trichinellosis, which ...affected ethnic minorities living in remote mountainous areas of northwestern Vietnam from 1970 to 2012. Trichinellosis was diagnosed in 126 patients, of which 11 (8.7%) were hospitalized and 8 (6.3%) died. All infected people had consumed raw pork from backyard and roaming pigs or wild boar at wedding, funeral, or New Year parties. The short incubation period (average of 9.5 days), the severity of the symptoms, which were characterized by diarrhea, abdominal pain, fever, myalgia, edema, weight loss, itch, and lisping, and the high mortality, suggest that patients had ingested a high number of larvae. The larval burden in pigs examined in one of the outbreaks ranged from 70 to 879 larvae/g. These larvae and those collected from a muscle biopsy taken from a patient from the 2012 outbreak were identified as Trichinella spiralis. Data presented in this work show that the northern regions of Vietnam are endemic areas for Trichinella infections in domestic pigs and humans.
We aimed to evaluate the microbiological characteristics and risk factors for mortality of infective endocarditis in two tertiary hospitals in Ho Chi Minh City, south Vietnam.
A retrospective study ...of 189 patients (120 men, 69 women; mean age 38 ± 18 years) with the diagnosis of probable or definite infective endocarditis (IE) according to the modified Duke Criteria admitted to The Heart Institute or Tam Duc Hospital between January 2005 and December 2014.
IE was related to a native valve in 165 patients (87.3%), and prosthetic valve in 24 (12.7%). Of the 189 patients in our series, the culture positive rate was 70.4%. The most common isolated pathogens were Streptococci (75.2%), Staphylococci (9.8%) followed by gram negative organism (4.5%). The sensitivity rate of Streptococci to ampicillin, ceftriaxone or vancomycin was 100%. The rate of methicillin resistant Staphylococcus aureus was 40%. There was a decrease in penicillin sensitivity for Streptococci over three eras: 2005-2007 (100%), 2008-2010 (94%) and 2010-2014 (84%). The in-hospital mortality rate was 6.9%. Logistic regression analysis found prosthetic valve and NYHA grade 3 or 4 heart failure and vegetation size of more than 15 mm as strong predictors of in-hospital mortality.
Streptococcal species were the major pathogen of IE in the recent years with low rates of antimicrobial resistance. Prosthetic valve involvement, moderate or severe heart failure and vegetation size of more than 15 mm were independent predictors for in-hospital mortality in IE.
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