The Importance of Secretor-Status in Norovirus Infection Following Allogeneic Hematopoietic Stem Cell Transplantation.

Background. Human secretor-status is a strong susceptibility factor for norovirus infection in immunocompetent people. The predominant norovirus genotype GII.4 almost exclusively infects secretors and is also associated with more severe symptoms. However, it is not known to what extent this also applies to immunocompromised individuals. Our objective was to determine the importance of secretor-status and norovirus genotype for the susceptibility and/or the clinical course of norovirus infection in allogeneic hematopoietic stem cell transplant (HCT) patients. Methods: This was a retrospective study of 89 HCT patients diagnosed with norovirus infection. Secretor-status and norovirus genotype were determined using stored extracted DNA or blood (n = 89) and fecal samples (n = 22), respectively. Results: Seven of eighty-nine (8%) of the patients were secretor-negative, a small proportion compared to the expected rate of at least 20% non-secretors in the general Swedish population. Among the genotyped samples, norovirus genotype GII.4 was predominant (n = 12) and only detected in secretor-positive individuals. Patients with norovirus GII.4 had a median symptom duration of 36 (3-681) days compared to 15 (1-94) days in patients infected with other norovirus genotypes (n = 10, p = 0.1). Conclusions: The results suggest that secretor-status affects the susceptibility to norovirus infection even when the immune system is severely compromised. The norovirus genotype may also be a risk factor for chronic norovirus symptoms in immunocompromised patients.

Hepatitis E virus is an infrequent but potentially serious infection in allogeneic hematopoietic stem cell transplant recipients.

Hepatitis E virus (HEV) can cause chronic infection and liver cirrhosis in immunocompromised individuals. The frequency and clinical importance of HEV was studied retrospectively in a cohort of 236 Swedish allogeneic hematopoietic stem cell transplantation (HSCT) recipients. In blood samples collected at 6 months after HSCT, HEV RNA was identified in 8/236 (3.4%) patients, and 11/236 (4.7%) patients had detectable anti-HEV IgG and/or IgM, eight of whom were HEV RNA negative. Two of the patients with positive HEV RNA died with ongoing signs of hepatitis: one of acute liver and multiple organ failure, the other of unrelated causes. The remaining six patients with HEV RNA had cleared the infection at 7-24 (median 8.5) months after HSCT. HEV infection was associated with elevated alanine aminotransferase at 6 months after HSCT (OR 15, 1.3-174, p = 0.03). Active graft-versus-host disease of the liver at 6 months after HSCT was present in 3/8 (38%) patients with HEV RNA, but was not significantly associated with HEV infection. In conclusion, HEV infection is an important differential diagnosis in patients with elevated liver enzymes after HSCT. Although spontaneous clearance was common, the clinical course may be severe.

Norovirus causing severe gastrointestinal disease following allogeneic hematopoietic stem cell transplantation: A retrospective analysis.

BACKGROUND: Norovirus (NV) can cause chronic and severe gastroenteritis with possible lethal outcome in immunocompromised patients. The knowledge of NV infections in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is limited. The aim of this study was to clarify the clinical importance of NV in a large cohort of HSCT recipients. METHODS: All patients undergoing HSCT and diagnosed with NV at Karolinska University Hospital from 2006-2012 were included in the study (63 patients). Clinical data were collected from medical records, and statistics were performed using the logistic regression method. RESULTS: The majority of patients (70%) had short-term symptoms (≤14 days). However, 54% of all patients required admission or prolonged hospitalization owing to the infection. In 16% of the patients the symptoms were chronic (>30 days), and in all but one of these patients the clinical picture also was severe, with malnutrition requiring long-term TPN, or serious dehydration. Severe combined immune deficiency (SCID) diagnosis was associated with chronic symptoms of NV infection (OR 30.3, CI 2.5-368). CONCLUSION: NV is an important pathogen in the HSCT setting, although the infection seems to be mild in most patients. Increased knowledge is needed to further identify risk factors for a severe course of NV infection in HSCT patients.

Detection of healthcare-associated urinary tract infection in Swedish electronic health records.

The prevalence of healthcare-associated infections (HAI) stresses the need for automatic surveillance in order to follow the effect of preventive measures. A number of detection systems have been set up for several languages, but none is known for Swedish hospitals. We plan a series of infection type specific programs for detection of HAI in electronic health records at a Swedish university hospital. Also, we aim at detecting HAI for patients entering hospital with HAI from previous care, a task that is not often addressed. This first study aims at surveillance of healthcare-associated urinary tract infections. The created rule-based system depends on acquiring the essential clinical information, and a combination of data and text mining is used. The wide range of diverse clinics with different traditions of documentation poses difficulties for detection. Results from evaluation on 1,867 care episodes from Oncology and Surgery show high precision (0.98), specificity (0.99) and negative predictive value (0.99), but an intermediate recall (0.60). An error analysis of the evaluation is presented and discussed.

["Bacterial scouting" to reduce healthcare associated infections. New method can identify and address risk factors for disease transmission]. / Bakterie-spaning« för att minska vårdrelaterade infektioner - Ny metod kan identifiera och åtgärda riskfaktorer för smittspridning.

This is a report of a multidisciplinary project conducted at Karolinska University Hospital in Stockholm. The aim was to study and reduce potential risk factors for the spread of health-care associated infections in the near-patient environment. A process beginning with an observation study conducted by two observers of which one was an industrial designer or a psychologist was used. Bacterial screenings were used to verify factors identified during the observations. The main focus of activities to reduce the identified risks was mainly to improve the cleaning. Improved cleaning routines reduced the microbiological level significantly.

Artemether-lumefantrine treatment failure despite adequate lumefantrine day 7 concentration in a traveller with Plasmodium falciparum malaria after returning from Tanzania.

Artemether-lumefantrine is currently first-line therapy of Plasmodium falciparum malaria in many countries. This report describes a treatment failure despite adequate drug concentrations in a traveller returning from sub-Saharan Africa. Genotyping confirmed recrudescence and suggested reduced sensitivity. Potential sub-optimal effect of artemether-lumefantrine highlights the need to follow non-immune individuals the weeks after treatment.

Respiratory syncytial virus infection in recipients of allogeneic stem-cell transplantation: a retrospective study of the incidence, clinical features, and outcome.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of serious respiratory infections in hematopoietic stem-cell transplant (HSCT) recipients. We aimed to determine the frequency, risk factors, and outcome of RSV infection in allo-HSCT recipients. DESIGN AND METHODS: Data were collected from 275 allo-HSCT recipients and identified 32 patients (11.6%, 26 adults and 6 children) RSV infection. A control group was selected matched for age, conditioning intensity and regimens, year of transplant. RESULTS: Eighteen patients had upper and 14 had lower respiratory tract infection (LRTI). The duration of viral shedding was long (20 days; 7-84). Twenty-eight patients received ribavirin (6 received intravenously, 11 orally, 9 both, 1 oral +aerosolized, and 1 received all three forms). The median duration of therapy was 22.5 days (7-54 days). Three (1.1% of entire cohort, 9.4% of infected patients; 21.4% of patients with LRTI) patients died from the RSV (attributable mortality), whereas two patients died from other subsequent infections 38 days to 5 months after diagnosis of RSV. Seven patients died from progression of underlying disease. Long-term respiratory function was assessed in 14 patients. Two patients died from respiratory failure. Three of 14 patients developed marked respiratory dysfunction after SCT. Three of 16 patients in the RSV group had normal respiratory function compared with 18 of 26 in the control group (P<0.01). CONCLUSION: RSV infection results in a low overall attributable mortality after allo-HSCT, but progression of the infection to LRTI is associated with increased risk for death. Late respiratory dysfunction is more common among patients, experienced RSV infection compared with controls.

Risk factors for the development of cytomegalovirus disease after allogeneic stem cell transplantation.

BACKGROUND AND OBJECTIVES: Cytomegalovirus (CMV) disease remains an important complication of allogeneic stem cell transplantation (SCT). We studied viral load kinetics and correlated the viral load and other transplant factors with the development of CMV disease. DESIGN AND METHODS: We studied 162 consecutive patients who were CMV seropositive or had CMV seropositive donors. Quantification of CMV DNA was performed by real-time polymerase chain reaction. RESULTS: CMV DNA detected was detected in 105 of the 162 patients. The mean peak viral loads were similar at first and subsequent reactivations. The serologic status of the donors and recipients prior to SCT significantly influenced the viral load. The cumulative incidence of CMV disease was 1.8% at 100 days and 6.3% at 365 days after SCT. The peak viral load were higher in patients who developed CMV disease than in patients without CMV disease (log10 3.5; SE +/- 0.26/200,000 cells vs. log10 2.7; SE +/- 0.09/200,000 cells; p=0.02). However, in multivariate analysis, only acute graft-versus-host disease (GVHD) grade II-IV and a graft from a CMV-negative donor to a CMV-positive patient were significant risk factors for CMV disease. In patients who required more than one course of pre-emptive therapy, acute GVHD and the rate of decrease in viral load during first pre-emptive therapy were significant risk factors for subsequent development of CMV disease. INTERPRETATION AND CONCLUSIONS: A decrease in viral load during pre-emptive therapy is an important factor for later development of CMV disease.

The value of CMV and fungal PCR for monitoring for acute leukaemia and autologous stem cell transplant patients.

Both CMV and fungal infections have been suggested to be causes of fever of unknown origin (FUO) in neutropenic patients. The aim of this prospective, blinded study was to use nucleic acid techniques for monitoring of 20 acute leukemia and 15 autologous stem cell transplant (SCT) patients. Blood samples were taken weekly and examined for fungal and CMV DNA by PCR and CMV mRNA by NASBA. 387 samples were analysed. Fungal DNA was detected in 9 samples. Four samples were positive for Aspergillus and 6 for Candida DNA (1 sample positive for both). Candida PCR was positive in 2 patients with FUO, 1 patient with a bacterial infection, 1 patient with fungaemia, and in 1 afebrile patient. Three patients had verified Candida infections. One was PCR positive and 2 were negative. Three patients with positive Aspergillus PCR had pneumonias and 1 patient had a FUO. CMV DNA was found in 19 samples from 15 CMV seropositive patients. CMV mRNA was detected in 1 sample. Two patients had infections possibly caused by CMV. No antiviral therapy was give and both recovered. PCR for Aspergillus might be helpful for the diagnosis of pneumonia while neither CMV nor Candida PCR conferred diagnostic benefits in this study.