Effects of surface-attached durations, nutrients, and relative humidity on the resuspension of bacteria during human walking.

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.

Pneumocystis jirovecii-related spontaneous pneumothorax, pneumomediastinum and subcutaneous emphysema in a liver transplant recipient: a case report.

BACKGROUND: 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%. CASE PRESENTATION: 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. CONCLUSION: 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.

Lipid metabolites as potential diagnostic and prognostic biomarkers for acute community acquired pneumonia.

Early diagnosis of acute community-acquired pneumonia (CAP) is important in patient triage and treatment decisions. To identify biomarkers that distinguish patients with CAP from non-CAP controls, we conducted an untargeted global metabolome analysis for plasma samples from 142 patients with CAP (CAP cases) and 97 without CAP (non-CAP controls). Thirteen lipid metabolites could discriminate between CAP cases and non-CAP controls with area-under-the-receiver-operating-characteristic curve of >0.8 (P ≤ 10(-9)). The levels of glycosphingolipids, sphingomyelins, lysophosphatidylcholines and L-palmitoylcarnitine were higher, while the levels of lysophosphatidylethanolamines were lower in the CAP cases than those in non-CAP controls. All 13 metabolites could distinguish CAP cases from the non-infection, extrapulmonary infection and non-CAP respiratory tract infection subgroups. The levels of trihexosylceramide (d18:1/16:0) were higher, while the levels of lysophosphatidylethanolamines were lower, in the fatal than those of non-fatal CAP cases. Our findings suggest that lipid metabolites are potential diagnostic and prognostic biomarkers for CAP.

Metabolomic Profiling of Plasma from Patients with Tuberculosis by Use of Untargeted Mass Spectrometry Reveals Novel Biomarkers for Diagnosis.

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-4ß-methyl-5α-cholesta-8-en-3ß-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-4ß-methyl-5α-cholesta-8-en-3ß-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-4ß-methyl-5α-cholesta-8-en-3ß-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.

Circulating cytomegalic cells in a patient with advanced HIV presenting with cytomegalovirus rhinosinusitis.

We report a patient with newly diagnosed late-stage HIV presenting with fever, rhinosinusitis and cognitive impairment. Analysis of cerebrospinal fluid and nasal turbinate tissue confirmed cytomegalovirus (CMV) infection. CMV pp65 antigen assay conducted on peripheral blood leukocytes revealed large CMV infected mononuclear cells (diameter ∼ 50 µm) with an unusual cytoplasmic pattern of pp65 staining. These large cells were also seen in buffy coat Wright's stained smears; their size, morphology and pp65 antigen uptake pattern were consistent with CMV infected cytomegalic endothelial cells. While CMV sinus infections are occasionally encountered in AIDS patients, this is the first report to document CMV infection of the nasal mucosa with secondary sinusitis and chronic suppurative otitis media. Furthermore, the detection of circulating cytomegalic cells is described--a rare finding with pathological and clinical significance in immunocompromised patients with CMV disease.

Fatal empyema thoracis caused by Schizophyllum commune with cross-reactive cryptococcal antigenemia.

We report a fatal case of Schizophyllum commune empyema thoracis with cross-reactive cryptococcal antigenemia. In vitro testing confirmed the ability of the fungus to cause a positive cryptococcal antigen latex agglutination system (CALAS) test result. Such a result may lead to delay in diagnosis and treatment, as most strains of S. commune are resistant to fluconazole.

Haemophagocytic lymphohistiocytosis: an uncommon clinical presentation of tuberculosis.

Secondary haemophagocytic lymphohistiocytosis is a rare but fatal complication of tuberculosis. We describe two cases, and review the local and international experience on the management of this clinical entity. Prompt treatment with anti-tuberculous drugs forms the cornerstone of therapeutic success.

High mortality associated with Catabacter hongkongensis bacteremia.

Catabacter hongkongensis is a recently described catalase-positive, motile, anaerobic, nonsporulating, Gram-positive coccobacillus that was first isolated from blood cultures of four patients from Hong Kong and Canada. Although DNA sequences representing C. hongkongensis have been detected in environmental sources, only one additional case of human infection has been reported, in France. We describe five cases of C. hongkongensis bacteremia in Hong Kong, two presenting with sepsis, one with acute gangrenous perforated appendicitis, one with acute calculous cholecystitis, and one with infected carcinoma of colon. Three patients, with gastrointestinal malignancy, died during admission. All five isolates were catalase positive, motile, and negative for indole production and nitrate reduction and produced acid from arabinose, glucose, mannose, and xylose. They were unambiguously identified as C. hongkongensis by 16S rRNA gene analysis. Of the total of 10 reported cases of C. hongkongensis bacteremia in the literature and this study, most patients had underlying diseases, while two cases occurred in healthy young individuals with acute appendicitis. Six patients presented with infections associated with either the gastrointestinal or biliary tract, supporting the gastrointestinal tract as the source of bacteremia. C. hongkongensis bacteremia is associated with a poor prognosis, with a high mortality of 50% among reported cases, especially in patients with advanced malignancies. All reported isolates were susceptible to metronidazole. Identification of more C. hongkongensis isolates by 16S rRNA gene sequencing will help better define its epidemiology and pathogenesis.

Clinical and virological factors associated with viremia in pandemic influenza A/H1N1/2009 virus infection.

BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION: 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.

Prevention of nosocomial transmission of norovirus by strategic infection control measures.

BACKGROUND: Nosocomial outbreaks of norovirus infection pose a great challenge to the infection control team. METHODS: Between November 1, 2009, and February 28, 2010, strategic infection control measures were implemented in a hospital network. In addition to timely staff education and promotion of directly observed hand hygiene, reverse-transcription polymerase chain reaction for norovirus was performed as an added test by the microbiology laboratory for all fecal specimens irrespective of the request for testing. Laboratory-confirmed cases were followed up by the infection control team for timely intervention. The incidence of hospital-acquired norovirus infection per 1,000 potentially infectious patient-days was compared with the corresponding period in the preceding 12 months, and the incidence in the other 6 hospital networks in Hong Kong was chosen as the concurrent control. Phylogenetic analysis of norovirus isolates was performed. RESULTS: Of the 988 patients who were tested, 242 (25%) were positive for norovirus; 114 (47%) of those 242 patients had norovirus detected by our added test. Compared with the corresponding period in the preceding 12 months, the incidence of hospital-acquired norovirus infection decreased from 131 to 16 cases per 1,000 potentially infectious patient-days (P < .001), although the number of hospital-acquired infections was low in both the study period (n = 8) and the historical control periods (n = 11). The incidence of hospital-acquired norovirus infection in our hospital network (0.03 cases per 1,000 patient-days) was significantly lower than that of the concurrent control (0.06 cases per 1,000 patient-days) (P = .015). Forty-three (93%) of 46 norovirus isolates sequenced belonged to the genogroup II.4 variant. CONCLUSIONS: Strategic infection control measures with an added test may be useful in controlling nosocomial transmission of norovirus.

Pneumococcal native aortic valve endocarditis with mycotic abdominal aortic aneurysm, paraspinal and iliopsoas abscesses and pneumonia revealing a multiple myeloma.

We report a rare case of multiple myeloma presenting with native aortic valve endocarditis with secondary embolic mycotic abdominal aortic aneurysm, contiguous paraspinal and iliopsoas abscesses, and pneumonia due to Streptococcus pneumoniae in a Chinese man. He was treated with aortic valve replacement, endovascular stenting of aneurysm, image-guided drainage of abscesses, and a 6-week course of endocarditic antibiotic therapy followed by chronic suppressive antibiotic therapy. Cases of multiple myeloma presenting with invasive pneumococcal infection were reviewed.

Sequential introduction of single room isolation and hand hygiene campaign in the control of methicillin-resistant Staphylococcus aureus in intensive care unit.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Concurrent comparison of epidemiology, clinical presentation and outcome between adult patients suffering from the pandemic influenza A (H1N1) 2009 virus and the seasonal influenza A virus infection.

PURPOSE OF STUDY: The demographics, clinical features and outcome of patients with pandemic influenza A (H1N1) 2009 infection were compared with a concurrent cohort of patients with seasonal influenza A infection. STUDY DESIGN: The clinical and microbiological data of hospitalised adult patients admitted between 29 June and 28 October 2009, with pandemic A (H1N1) 2009 or seasonal influenza A infection, were analysed. RESULTS: A total of 186 patients including 69 pandemic A (H1N1) and 117 seasonal influenza were analysed. The majority (75%) under 50 years of age had pandemic A (H1N1). Compared with seasonal influenza, pandemic A (H1N1) patients were younger (median age 47 years vs 76 years, p<0.001), less likely to have lower respiratory tract symptoms (46.4% vs 66.7%, p=0.007), but more likely to be obese (5.8% vs 0%, p=0.018), pregnant (7.2% vs 0.9%, p=0.027) or have no underlying predisposing factors (24.6% vs 5.1%, p<0.001). Patients with pandemic A (H1N1) were more likely to receive oseltamivir (91.3% vs 40.2%, p<0.001), but less likely to receive antibiotics (75.4% vs 90.6%, p=0.005). Respiratory failure was the reason for intensive care unit admission for all four patients with pandemic A (H1N1), but only for one of three patients with seasonal influenza. There were no statistical significant differences in the rate of intensive care unit admission or death. CONCLUSIONS: In addition to age, several clinical parameters were different between pandemic A (H1N1) and seasonal influenza. However, since both seasonal and pandemic influenza can lead to significant morbidity and mortality, the impact of pre-existing seasonal influenza should not be underestimated during the pandemic period.

Capnocytophaga sputigena primary iliopsoas abscess.

Iliopsoas abscess is usually secondary to the spread of infection from a contiguous focus. Primary disease is uncommon, except in children where Staphylococcus aureus is the main pathogen. We report a 60-year-old woman who developed a primary iliopsoas abscess as a result of haematogenous spread of Capnocytophaga sputigena from a palatal fistula and chronic sinusitis due to previous treatment for nasopharyngeal carcinoma. Pyomyositis due to unusual and fastidious Gram-negative bacilli should be considered in patients with head and neck tumours who have previously received radiotherapy.

Epidemiology and clinical features of Shewanella infection over an eight-year period.

Shewanella is a rare human pathogen that can lead to fatal infections. However, clinical information about this bacterium remains scarce. In this study, we retrospectively reviewed all patients with laboratory isolates of Shewanella over an 8-y period to assess risk factors, clinical manifestations and outcome. Twenty-nine patients were identified. Shewanella was most commonly isolated from intra-abdominal specimens (48.2%), followed by skin and soft tissue specimens (27.6%), blood (13.8%) and sputum (10.3%). Malignancy, hepatobiliary disease and diabetes mellitus were common underlying diseases. The overall 30-day mortality rate was 20.6%. Shewanella was considered a definite causative pathogen in 7 patients, and a recurrent infection occurred in 2 patients. Colonization of the biliary tract was common. Among co-isolated pathogens, the enteric flora was most represented. All isolates were susceptible to ceftazidime and aminoglycosides, but 1 isolate was resistant to imipenem. In conclusion, Shewanella may become a colonizing bacterium, subsequently causing invasive diseases in patients with an underlying disease.

Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection.

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.

Viral load in patients infected with pandemic H1N1 2009 influenza A virus.

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 10(8) copies/ml for pandemic H1N1 virus compared with 3.28 x 10(8) 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.

Coccidioidomycosis as a rare cause of pneumonia in non-endemic areas: a short exposure history should not be ignored.

Coccidioidomycosis is endemic in the south-western USA. Two cases of infection in travellers returning to Hong Kong are described. A previously healthy patient who had travelled to an endemic area for a short time was successfully treated with fluconazole. A second patient with comorbidities and more prolonged exposure had disseminated and eventually fatal disease, despite prolonged administration of anti-fungal agents. Although coccidioidomycosis is a rare disease in Hong Kong, it should always be considered when there is a relevant travel history. Even a short period of travel to an endemic area should alert clinicians to this possibility when managing patients with severe pneumonia, especially those with multi-organ involvement. On the other hand, in patients with comorbidities, even aggressive and prolonged anti-fungal therapy may not guarantee a successful outcome.

Outbreak of intestinal infection due to Rhizopus microsporus.

Sinopulmonary and rhinocerebral zygomycosis has been increasingly found in patients with hematological malignancies and bone marrow transplantation, but intestinal zygomycosis remains very rare in the literature. We investigated an outbreak of intestinal infection due to Rhizopus microsporus in 12 patients on treatment for hematological malignancies over a period of 6 months in a teaching hospital. The intake of allopurinol during hospitalization (P < 0.001) and that of commercially packaged ready-to-eat food items in the preceding 2 weeks (P < 0.001) were found to be independently significant risk factors for the development of intestinal zygomycosis. A total of 709 specimens, including 378 environmental and air samples, 181 food samples, and 150 drug samples, were taken for fungal culture. Among them, 16 samples of allopurinol tablets, 3 prepackaged ready-to-eat food items, and 1 pair of wooden chopsticks were positive for Rhizopus microsporus, which was confirmed by ITS1-5.8S-ITS2 rRNA gene cluster (internal transcribed spacer [ITS]) sequencing. The mean viable fungal counts of allopurinol obtained from wards and pharmacy were 4.22 x 10(3) CFU/g of tablet (range, 3.07 x 10(3) to 5.48 x 10(3)) and 3.24 x 10(3) CFU/g of tablet (range, 2.68 x 10(3) to 3.72 x 10(3)), respectively, which were much higher than the mean count of 2 x 10(2) CFU/g of food. Phylogenetic analysis by ITS sequencing showed multiple clones from isolates of contaminated allopurinol tablets and ready-to-eat food, of which some were identical to patients' isolates, and with one isolate in the cornstarch used as an excipient for manufacture of this drug. We attempted to type the isolates by random amplification of polymorphic DNA analysis, with limited evidence of clonal distribution. The primary source of the contaminating fungus was likely to be the cornstarch used in the manufacturing of allopurinol tablets or ready-to-eat food. Rhizopus microsporus is thermotolerant and can multiply even at 50 degrees C. The long holding time of the intermediates during the manufacturing process of allopurinol amplified the fungal load. Microbiological monitoring of drugs manufactured for highly immunosuppressed patients should be considered.

Retracted: outcome and immune reconstitution of HBV-specific immunity in patients with reactivation of occult HBV infection after alemtuzumab-containing chemotherapy regimen.

UNLABELLED: Whether preemptive anti- hepatitis B virus (HBV) therapy should be considered in all hepatitis B surface antigen (HBsAg)-negative patients with occult HBV infection receiving alemtuzumab containing chemotherapy is uncertain. We determined the outcome and effect on HBV-specific immunity of an alemtuzumab-containing chemotherapy regimen in occult HBV-infected patients. Twenty-one consecutive occult HBV-infected patients treated with an alemtuzumab containing chemotherapy regimen were studied. T cell reactivity to HBV antigens and -peptides were quantified by ELISpot and the T cell subset by flow cytometry. Six of the 21 patients (28.6%) developed HBsAg seroreversion. The median (range) time to development of HBsAg seroreversion after the end of chemotherapy was 1.8 months (0.2-2.3 months). Direct sequencing showed that the occult HBV infection of all six patients (100%) was reactivated. These six patients developed severe HBV-related hepatitis. At the end of follow-up, four of these six patients (66.7%) had become negative for HBsAg again. Recovery of CD4+ T cell count and CD4+T cell reactivity against hepatitis B core antigen (HBcAg) occurred 9 months after the end of chemotherapy. Loss of HBsAg occurred after recovery of the CD4+T cell count and increased CD4+T cell reactivity against HBcAg 9 months after the end of chemotherapy. CONCLUSION: An alemtuzumab-containing chemotherapy regimen is associated with a high risk of reactivation of occult HBV infection. Suppression of HBV immunity by an alemtuzumab-containing chemotherapy regimen would persist until 9 months after the end of chemotherapy. In occult HBV-infected patients receiving an alemtuzumab-containing chemotherapy regimen, preemptive anti-HBV therapy should be continued until 9 months after the end of chemotherapy, when recovery of HBV immunity has occurred.