Positive detection of viral RNA in blood and other non-respiratory specimens occurs in severe human influenza A/H5N1 viral infection but is not known to occur commonly in seasonal human influenza ...infection. Recently, viral RNA was detected in the blood of patients suffering from severe pandemic influenza A/H1N1/2009 viral infection, although the significance of viremia had not been previously studied. Our study aims to explore the clinical and virological factors associated with pandemic influenza A/H1N1/2009 viremia and to determine its clinical significance.
Clinical data of patients admitted to hospitals in Hong Kong between May 2009 and April 2010 and tested positive for pandemic influenza A/H1N1/2009 was collected. Viral RNA was detected by reverse-transcription polymerase chain reactions (RT-PCR) targeting the matrix (M) and HA genes of pandemic influenza A/H1N1/2009 virus from the following specimens: nasopharyngeal aspirate (NPA), endotracheal aspirate (ETA), blood, stool and rectal swab. Stool and/ or rectal swab was obtained only if the patient complained of any gastrointestinal symptoms. A total of 139 patients were included in the study, with viral RNA being detected in the blood of 14 patients by RT-PCR. The occurrence of viremia was strongly associated with a severe clinical presentation and a higher mortality rate, although the latter association was not statistically significant. D222G/N quasispecies were observed in 90% of the blood samples.
Presence of pandemic influenza A/H1N1/2009 viremia is an indicator of disease severity and strongly associated with D222G/N mutation in the viral hemagglutinin protein.
Resuspension caused by human walking activities is an important source of indoor bioaerosols and has been associated with health effects such as allergies and asthma. However, it is unknown whether ...inhalation of resuspended bioaerosols is an important exposure pathway for airborne infection. Also, crucial factors influencing the resuspension of settled microbes have not been quantified. In this study, we experimentally investigated the resuspension of culturable bacteria from human-stepping on polyvinyl chloride (PVC) flooring under different conditions. We determined the bacterial resuspension emission factor (ER), a normalized resuspension parameter for the ratio of resuspended mass in the air to the mass of settled particles, for two common bacteria, Escherichia coli and Salmonella enterica. The investigation involved varying factors such as microbial surface-attached durations (0, 1, 2, and 3 days), the absence or presence of nutrients on flooring surfaces, and changes in relative humidity (RH) (35%, 65%, and 85%). The results showed that, in the absence of nutrients, the highest ER values for E. coli and S. enterica were 3.8 × 10−5 ± 5.2 × 10−6 and 5.3 × 10−5 ± 6.0 × 10−6, respectively, associated with surface-attached duration of 0 days. As the surface-attached duration increased from 0 to 3 days, ER values decreased by 92% and 84% for E. coli and S. enterica, respectively. In addition, we observed that ER values decreased with the increasing RH, which is consistent with particle adhesion theory. This research offers valuable insights into microbial resuspension during human walking activities and holds the potential for assisting in the assessment and estimation of risks related to human exposure to bioaerosols.
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•Bacterial resuspension from flooring during human walking was quantified.•Resuspensions of Escherichia coli and Salmonella enterica were measured.•Effects of microbial surface-attached durations, nutrients, and RH were studied.•Bacterial resuspension decreased with increasing RH and surface-attached durations.
Background. Experience from treating patients with Spanish influenza and influenza A(H5N1) suggested that convalescent plasma therapy might be beneficial. However, its efficacy in patients with ...severe pandemic influenza A(H1N1) 2009 virus (H1N1 2009) infection remained unknown. Methods. During the period from 1 September 2009 through 30 June 2010, we conducted a prospective cohort study by recruiting patients aged ≥ 18 years with severe H1N1 2009 infection requiring intensive care. Patients were offered treatment with convalescent plasma with a neutralizing antibody titer of ≥1:160, harvested by apheresis from patients recovering from H1N1 2009 infection. Clinical outcome was compared with that of patients who declined plasma treatment as the untreated controls. Results. Ninety-three patients with severe H1N1 2009 infection requiring intensive care were recruited. Twenty patients (21.5%) received plasma treatment. The treatment and control groups were matched by age, sex, and disease severity scores. Mortality in the treatment group was significantly lower than in the nontreatment group (20.0% vs 54.8%; P = .01). Multivariate analysis showed that plasma treatment reduced mortality (odds ratio OR, .20; 95% confidence interval CI, .06-.69; P = .011), whereas complication of acute renal failure was independently associated with death (OR, 3.79; 95% CI, 1.15-12.4; P = .028). Subgroup analysis of 44 patients with serial respiratory tract viral load and cytokine level demonstrated that plasma treatment was associated with significantly lower day 3, 5, and 7 viral load, compared with the control group (P < .05). The corresponding temporal levels of interleukin 6, interleukin 10, and tumor necrosis factor α (P < .05) were also lower in the treatment group. Conclusions. Treatment of severe H1N1 2009 infection with convalescent plasma reduced respiratory tract viral load, serum cytokine response, and mortality.
Viral shedding profile of infections caused by the pandemic H1N1 2009 influenza A virus has not been reported. The aim of this study was to determine the viral load in different body sites. Viral ...loads of pandemic H1N1 virus in respiratory specimens, stool, urine, and serum were determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Respiratory specimens from patients with seasonal influenza were used as historical controls. Initial pre-treatment viral load were compared between these two groups. Serial respiratory specimens from patients with pandemic H1N1 virus infection were obtained for analysis of viral dynamics. Twenty-two pandemic H1N1 cases and 44 seasonal influenza historical controls were included. The mean initial viral load before oseltamivir therapy was 1.84 x 10⁸ copies/ml for pandemic H1N1 virus compared with 3.28 x 10⁸ copies/ml in seasonal influenza historical controls (P = 0.085). Among patients with pandemic H1N1 virus infection, peak viral load occurred on the day of onset of symptoms, and declined gradually afterwards, with no virus being detectable in respiratory specimens by RT-PCR 8 days and by culture 5 days after the onset of symptoms respectively, except in one patient. Pandemic H1N1 virus was detected in stool and in urine from 4/9 and 1/14 patients, respectively. Viral culture was also positive from the stool sample with the highest viral load. Younger age was associated with prolonged shedding in the respiratory tract and higher viral load in the stool. Data from this quantitative analysis of viral shedding may have implications for formulating infection control measures. J. Med. Virol. 82:1-7, 2010.
Pneumocystis pneumonia (PCP) is a common opportunistic infection caused by Pneumocystis jirovecii. Its incidence at 2 years or more after liver transplant (LT) is < 0.1%. PCP-related spontaneous ...pneumothorax and/or pneumomediastinum is rare in patients without the human immunodeficiency virus, with an incidence of 0.4-4%.
A 65-year-old woman who had split-graft deceased-donor LT for primary biliary cirrhosis developed fever, dyspnea and dry coughing at 25 months after transplant. Her immunosuppressants included tacrolimus, mycophenolate mofetil, and prednisolone. PCP infection was confirmed by molecular detection of Pneumocystis jirovecii,in bronchoalveolar lavage. On day-10 trimethoprim-sulphamethoxazole, her chest X-ray showed subcutaneous emphysema bilaterally, right pneumothorax and pneumomediastinum. Computed tomography of the thorax confirmed the presence of right pneumothorax, pneumomediastinum and subcutaneous emphysema. She was managed with 7-day right-sided chest drain and a 21-day course of trimethoprim-sulphamethoxazole before discharge.
Longer period of PCP prophylaxis should be considered in patients who have a higher risk compared to general LT patients. High index of clinical suspicion, prompt diagnosis and treatment with ongoing patient reassessment to detect and exclude rare, potentially fatal but treatable complications are essential, especially when clinical deterioration has developed.
Background. Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological ...profile of different clinical severity are lacking. Methods. We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-without-ARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. Results. Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. Conclusions. The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death.
Although tuberculosis (TB) is a reemerging disease that affects people in developing countries and immunocompromised populations in developed countries, the current diagnostic methods are far from ...optimal. Metabolomics is increasingly being used for studies on infectious diseases. We performed metabolome profiling of plasma samples to identify potential biomarkers for diagnosing TB. We compared the plasma metabolome profiles of TB patients (n = 46) with those of community-acquired pneumonia (CAP) patients (n = 30) and controls without active infection (n = 30) using ultrahigh-performance liquid chromatography-electrospray ionization-quadrupole time of flight mass spectrometry (UHPLC-ESI-QTOFMS). Using multivariate and univariate analyses, four metabolites, 12R-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid 12(R)-HETE, ceramide (d18:1/16:0), cholesterol sulfate, and 4α-formyl-4β-methyl-5α-cholesta-8-en-3β-ol, were identified and found to have significantly higher levels in TB patients than those in CAP patients and controls. In a comparison of TB patients and controls, the four metabolites demonstrated area under the receiver operating characteristic curve (AUC) values of 0.914, 0.912, 0.905, and 0.856, sensitivities of 84.8%, 84.8%, 87.0%, and 89.1%, specificities of 90.0%, 86.7%, 86.7%, and 80.0%, and fold changes of 4.19, 26.15, 6.09, and 1.83, respectively. In a comparison of TB and CAP patients, the four metabolites demonstrated AUC values of 0.793, 0.717, 0.802, and 0.894, sensitivities of 89.1%, 71.7%, 80.4%, and 84.8%, specificities of 63.3%, 66.7%, 70.0%, and 83.3%, and fold changes of 4.69, 3.82, 3.75, and 2.16, respectively. 4α-Formyl-4β-methyl-5α-cholesta-8-en-3β-ol combined with 12(R)-HETE or cholesterol sulfate offered ≥70% sensitivity and ≥90% specificity for differentiating TB patients from controls or CAP patients. These novel plasma biomarkers, especially 12(R)-HETE and 4α-formyl-4β-methyl-5α-cholesta-8-en-3β-ol, alone or in combination, are potentially useful for rapid and noninvasive diagnosis of TB. The present findings may offer insights into the pathogenesis and host response in TB.
After renovation of the adult intensive care unit (ICU) with installation of ten single rooms, an enhanced infection control program was conducted to control the spread of methicillin-resistant ...Staphylococcus aureus (MRSA) in our hospital.
Since the ICU renovation, all patients colonized or infected with MRSA were nursed in single rooms with contact precautions. The incidence of MRSA infection in the ICU was monitored during 3 different phases: the baseline period (phase 1); after ICU renovation (phase 2) and after implementation of a hand hygiene campaign with alcohol-based hand rub (phase 3). Patients infected with extended spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella species were chosen as controls because they were managed in open cubicles with standard precautions.
Without a major change in bed occupancy rate, nursing workforce, or the protocol of environmental cleansing throughout the study period, a stepwise reduction in ICU onset nonbacteraemic MRSA infection was observed: from 3.54 (phase 1) to 2.26 (phase 2, p = 0.042) and 1.02 (phase 3, p = 0.006) per 1000-patient-days. ICU onset bacteraemic MRSA infection was significantly reduced from 1.94 (phase 1) to 0.9 (phase 2, p = 0.005) and 0.28 (phase 3, p = 0.021) per 1000-patient-days. Infection due to ESBL-producing organisms did not show a corresponding reduction. The usage density of broad-spectrum antibiotics and fluoroquinolones increased from phase 1 to 3. However a significant trend improvement of ICU onset MRSA infection by segmented regression analysis can only be demonstrated when comparison was made before and after the severe acute respiratory syndrome (SARS) epidemic. This suggests that the deaths of fellow healthcare workers from an occupational acquired infection had an overwhelming effect on their compliance with infection control measures.
Provision of single room isolation facilities and promotion of hand hygiene practice are important. However compliance with infection control measures relies largely on a personal commitment, which may increase when personal safety is threatened.
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