Pandemic (H1N1) 2009 Encephalitis in Woman, Taiwan

We report an unusual case of pandemic (H1N1) 2009–related encephalitis in an immunocompetent woman. Although rare cases of pandemic (H1N1) 2009 associated with encephalitis have been reported previously, in this patient, direct viral invasion of the central nervous system was shown by simultaneous detection of viral RNA and pleocytosis

Invasive fungal sinusitis in patients with hematological malignancy: 15 years experience in a single university hospital in Taiwan

<p>Abstract</p> <p>Background</p> <p>Risk factors and outcomes in hematological patients who acquire invasive fungal sinusitis (IFS) are infrequently reported in the modern medical era.</p> <p>Method</p> <p>A retrospective study of hospitalized patients with hematological disease was conducted at National Taiwan University Hospital between January 1995 and December 2009.</p> <p>Results</p> <p>Clinical characteristics and outcomes with their associated radiographic and microbiological findings were analyzed. Forty-six patients with IFS and 64 patients with chronic non-invasive sinusitis were enrolled as comparsion. IFS developed more commonly in patients with acute myeloid leukemia (AML) and with prolonged neutropenia (absolute neutrophil count less than 500/mm³for more than 10 days) (<it>p </it>< 0.001). <it>Aspergillus flavus </it>was the most common pathogen isolated (44%). Serum <it>Aspergillus </it>galactomannan antigen was elevated in seven of eleven patients (64%) with IFS caused by aspergillosis but negative for all three patients with mucormycosis. Bony erosion and extra-sinus infiltration was found in 15 of 46 (33%) patients on imaging. Overall, 19 of 46 patients (41.3%) died within 6 weeks. Patients with disease subtype of AML (p = 0.044; Odds Ratio [OR], 5.84; 95% confidence interval [95% CI], 1.02-30.56) and refractory leukemia status (p = 0.05; OR, 4.27; 95% CI, 1.003-18.15) had worse prognosis. Multivariate analysis identified surgical debridement as an independent good prognostic factor (p = 0.047) in patients with IFS.</p> <p>Conclusions</p> <p>Patients of AML with prolonged neutropenia (> 10 days) had significantly higher risk of IFS. Early introduction of anti-fungal agent and aggressive surgical debridement potentially decrease morbidity and mortality in high risk patients with IFS.</p

Clinical characteristics and outcomes of Mycobacterium tuberculosis disease in adult patients with hematological malignancies

BACKGROUND: Diseases caused by Mycobacterium tuberculosis (TB) among adult patients with hematological malignancies have rarely been investigated. METHODS: Adult patients with hematological malignancies at National Taiwan University Hospital between 1996 and 2009 were retrospectively reviewed. Patients with positive serology for HIV were excluded. TB disease is diagnosed by positive culture(s) in the presence of compatible symptoms and signs. The demographics, laboratory and, microbiological features, were analyzed in the context of clinical outcomes. RESULTS: Fifty-three of 2984 patients (1.78%) were diagnosed with TB disease. The estimated incidence was 120 per 100,000 adult patients with hematological malignancies. Patients with acute myeloid leukemia had a significantly higher incidence of TB disease than other subtypes of hematological malignancies (2.87% vs. 1.21%, p = 0.002, odds ratio, 2.40; 95% confidence interval, 1.39-4.41). Thirty-eight patients (72%) with non-disseminated pulmonary TB disease presented typically with mediastinal lymphadenopathy (53%), pleural effusion (47%) and fibrocalcific lesions (43%) on chest imaging. The 15 (28%) patients with extra-pulmonary disease had lower rates of defervescence within 72 h of empirical antimicrobial therapy (13% vs 45%, p = 0.03) and a higher 30-day in-hospital mortality (20% vs. 0%, p = 0.004) compared to those with disease confined to the lungs. CONCLUSIONS: TB disease is not uncommon among patients with hematological malignancies in Taiwan. Patients who received a diagnosis of extra-pulmonary TB suffered higher mortality than those with pulmonary TB alone. Clinicians should consider TB in the differential diagnoses of prolonged fever in patients with hematological malignancies, particularly in regions of high endemicity

Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19

: Pediatric Coronavirus Disease 2019 (pCOVID-19) is rarely severe; however, a minority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might develop multisystem inflammatory syndrome in children (MIS-C), with substantial morbidity. In this longitudinal multi-institutional study, we applied multi-omics (analysis of soluble biomarkers, proteomics, single-cell gene expression and immune repertoire analysis) to profile children with COVID-19 (n = 110) and MIS-C (n = 76), along with pediatric healthy controls (pHCs; n = 76). pCOVID-19 was characterized by robust type I interferon (IFN) responses, whereas prominent type II IFN-dependent and NF-κB-dependent signatures, matrisome activation and increased levels of circulating spike protein were detected in MIS-C, with no correlation with SARS-CoV-2 PCR status around the time of admission. Transient expansion of TRBV11-2 T cell clonotypes in MIS-C was associated with signatures of inflammation and T cell activation. The association of MIS-C with the combination of HLA A*02, B*35 and C*04 alleles suggests genetic susceptibility. MIS-C B cells showed higher mutation load than pCOVID-19 and pHC. These results identify distinct immunopathological signatures in pCOVID-19 and MIS-C that might help better define the pathophysiology of these disorders and guide therapy

Long-term immune responses and comparative effectiveness of one or two doses of 7-valent pneumococcal conjugate vaccine (PCV7) in HIV-positive adults in the era of combination antiretroviral therapy

Introduction: HIV infection impairs maintenance of immunological memory, yet few studies of HIV-positive adults receiving 7-valent pneumococcal conjugate vaccine (PCV7) have followed them beyond the first year. We determined and compared the durability of serological responses and the clinical outcomes of HIV-positive adults annually for five years following vaccination with one or two doses of PCV7. ;Methods: In this non-randomized clinical trial, 221 pneumococcal vaccine-naive HIV-positive adults receiving one (n = 109) or two doses four weeks apart (n = 112) of PCV7 between 2008 and 2010 were longitudinally followed for evaluation of significant serological response and for episodes of pneumonia and invasive pneumococcal disease. ;Results: At the time of vaccination, the two groups were well matched for age, risk factors, combination antiretroviral therapy (cART) coverage, CD4 count and plasma HIV RNA load (PVL). At the end of five years, the CD4 counts for the one-and two-dose groups had increased from 407 and 406 to 550 and 592 cells/mL, respectively, and 82.4 and 81.6% of the participants had fully suppressed PVL. Significant immune responses to &gt;= 2 serotypes persisted for 67.9 vs 78.6%, 64.2 vs 71.4%, 66.1 vs 71.4%, 57.8 vs 69.6% in the second, third, fourth and fifth years after one and two doses of PCV7 in the intention-to-treat analysis, respectively. In multivariate analysis, immunization with two doses of PCV7 (odds ratio (OR) 1.71, 95% confidence interval (CI) 1.10 to 2.65, p = 0.016), concurrent cART (OR 2.16, 95% CI 1.16 to 4.00, p = 0.015) and CD4 proliferation (OR 1.12, 95% CI 1.01 to 1.27, p = 0.031) were predictive of persistent serological responses in the fifth year. Only one patient in the one-dose group had documented pneumococcal pneumonia (non-bacteraemic) and none had invasive pneumococcal disease in the 6.5 years of follow-up. ;Conclusions: One or two doses of PCV7 achieve durable seroprotective responses in HIV-treated participants; however, two doses may be more robust than one dose in a larger study population or in real-world populations with less cART coverage

Bacteremia caused by Pantoea agglomerans at a medical center in Taiwan, 2000-2010

Background/Purpose: There are only three case reports of adult patients with spontaneous Pantoea agglomerans bacteremia in the English literature. The aim of this study was to investigate clinical and microbiologic characteristics patients of P agglomerans bacteremia. Methods: We studied all adult patients with P agglomerans bacteremia at a medical center from 2000 to 2010. The isolates were identified using two commercial identification systems. Results: Of the 18 patients identified, 72% (n = 13) had active gastroesophageal disease treated with antacids. Two-thirds of patients had indwelling central lines and advanced cancers. None of the removed catheter tips yielded P agglomerans and line persistence was not associated with adverse outcomes. Initial disease severity was low, hypotension was uncommon and no patient died of bacteremia. Recurrence of bacteremia occurred in one patient with deep-seated infection. 16srRNA gene sequencing identified only half of the isolates as P agglomerans. The remaining nine isolates were Enterobacter species for six, Pantoea ananatis for two, and Exiguobacterium profundum for one. There were no significant differences between the characteristics of the subgroup molecularly identified as P agglomernas and the overall group characteristics. Eleven (61%) of the 18 isolates were susceptible to cefazolin, six (33%) susceptible to fosfomycin (MIC &lt;= 64 mg/ml). Two isolates had colistin MICs &gt;= 4 mg/ml. Conclusion: Bacteremia caused by P agglomerans is associated with gastroesophageal reflux disease and receipt of antacids. 16srRNA gene sequencing should not be used as the sole basis for its identification and we have highlighted the need for another molecular-based technique to conclusively characterize P agglomerans. Copyright (C) 2012, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. All rights reserved

Survival of septic adults compared with nonseptic adults receiving extracorporeal membrane oxygenation for cardiopulmonary failure: A propensity-matched analysis

Purpose: Limited data on the outcomes of adults with active sepsis undergoing extracorporeal membrane oxygenation (ECMO) exist. Materials and Methods: We analyzed our prospective database for adults undergoing their first ECMO from 2001 to 2009. Patients with preexisting sepsis had newly emerging or uncontrolled infections precipitating refractory respiratory and/or circulatory failure within 7 days preceding ECMO. Propensity score matching was performed to equalize potential prognostic factors between patients with and patients without sepsis. Results: Of the 514 adults receiving their first ECMO, 108 with preexisting sepsis were matched with 108 without sepsis by propensity score. Overall survival to discharge did not differ between those with (28.7%) and those without sepsis (37.0%; P = .192). When venovenous ECMO and venoarterial ECMO were considered separately, survival tended to be worse for septic patients on venoarterial ECMO (24.4%) compared with nonseptic adults on venoarterial ECMO (34.9%; P = .147). After adjustments for age, stroke, acutemyocarditis, inter-extracorporeal cardiopulmonary resuscitation, and post-ECMO renal and neurologic deficits by multivariate analysis, the increased risk of mortality persisted for septic adults receiving venoarterial ECMO (hazard ratio, 2.54; 95% confidence intervals, 1.75-3.70; P &lt; .01). Patients on venovenous ECMO had similar outcomes regardless of preexisting sepsis. Conclusions: Preexisting sepsis is not a contraindication for ECMO. However, venoarterial ECMO should be used with caution, given active sepsis. (c) 2013 Elsevier Inc. All rights reserved

Predictors of survival in adults undergoing extracorporeal membrane oxygenation with severe infections

Background: To identify novel factors associated with the survival of septic adults receiving extracorporeal membrane oxygenation (ECMO) to improve patient selection and outcomes. ;Methods: Cases were identified from our ECMO registry from 2001 to 2011 if they were &gt;= 16 years and received ECMO for life-threatening sepsis. ;Results: A total of 151 adults with a median (25th-75th percentile) age of 51 (3763) years were analyzed. Pneumonia (50%), myocarditis (20%), and primary bloodstream infections (15%) were the main types of infection, caused by predominantly nonfermentative Gram-negative bacteria (NFGNB) (26%), Enterobacteriaceae (24%), and Gram-positive cocci (21%). The in-hospital mortality of patients with NFGNB, enteric, and Gram-positive bacterial pneumonias were 100%, 68%, and 14%, respectively. Using the Cox-proportional hazards model, we found that age&gt;75 years (hazard ratio [HR], 1.98, 95% confidence interval [95% CI], 1.30-3.02), pre-ECMO dialysis (HR, 3.20, 95% CI, 1.34-7.63), longer door-to-ECMO intervals (HR, 1.01, 95% CI, 1.00-1.02), venoarterial mode (HR, 2.58, 95% CI, 1.55-4.21), and fungal (HR, 2.83, 95% CI, 1.36-5.88) and NFGNB sepsis (HR, 2.48, 95% CI, 1.44-4.27) were associated with mortality. Gram-positive sepsis (HR, 0.20, 95% CI, 0.08-0.57), myocarditis (HR, 0.12, 95% CI, 0.06-0.27), pneumonia (HR, 0.54, 95% CI, 0.30-0.90), and effective empirical antimicrobial therapy were predictive of survival (HR, 0.57, 95% CI, 0.37-0.89); all P&lt;.05. Excluding the 67 heavily premorbid patients, we found that 54% survived ECMO and 42% survived to discharge, with significantly more survivors with door-to-ECMO times of &lt;= 96 hours than &gt;96 hours (59% vs 15%, P&lt;.0001). ;Conclusions: Better outcomes were associated with door-to ECMO times of 96 hours or less, for Gram-positive rather than Gram-negative sepsis, and for pneumonia rather than primary bloodstream infections

A Phase I, randomized, open-label study to evaluate the safety and immunogenicity of an enterovirus 71 vaccine

Background: Large-scale outbreaks of enterovirus 71 (EV71) infections have occurred in Asia-Pacific regions. Severe complications include encephalitis and poliomyelitis-like paralysis, cardiopulmonary collapse, and death, necessitating an effective vaccine against EV71. Methods: In this randomized Phase I study, we evaluated the safety and immunogenicity of an inactivated alum-adjuvanted EV71 whole-virus vaccine produced on Vero cell cultures. Sixty healthy volunteers aged 20-60 years received two doses of vaccine, administered 21 days apart. Each dose contained either 5 mu g of EV71 antigen with 150 mu g of adjuvant (Group A05) or 10 mu g of EV71 antigen with 300 mu g of adjuvant (Group B10). Serologic analysis was performed at baseline, day 21, and day 42. Results: There were no serious adverse events. Mild injection site pain and myalgia were the most common adverse events with either vaccine formulation. The immunogenicity data showed that 90% of vaccine recipients have a 4-fold or greater increase in neutralization antibody titers (NT) after the first dose, without a further increase in NT after the second dose. The seroconversion rates on day 21 and day 42 were 86.7% and 93.1% respectively, in Group A05, and 92.9% and 96.3%, respectively, in Group B10. Thus, 5 mu g and 10 mu g of the EV71 vaccine can induce a remarkable immune response in healthy adults after only the first vaccination. Conclusion: The 5 mu g and 10 mu g adjuvanted EV71 vaccines are generally safe and immunogenic in healthy adults. (c) 2013 Elsevier Ltd. All rights reserved