Beersma, M.F.C.

Unrecognized norovirus infections in health care institutions and their clinical impact (Article)

2012-09-01T00:00:00Z

Noroviruses (NoVs) have emerged as the leading cause of acute viral gastroenteritis (GE) in humans. Although diagnostic facilities have greatly improved, significant underdiagnosis of NoV in hospitals may still occur, thereby increasing clinical burden and nosocomial spread. We evaluated the underdiagnosis of sporadic NoV infections in a tertiary care hospital and estimated its clinical impact. From December 2008 until July 2009, fecal samples specifically referred for bacterial but not viral examination were retrospectively tested for NoV by real-time PCR. The clinical and virological data from patients with undiagnosed NoV infection (missed patients) were evaluated and compared with those from patients with recognized NoV. During the study period, 45 patients with undiagnosed NoV were detected, whereas 50 patients were regularly diagnosed. The missed NoV cases were more frequently adults than children (80% versus 46%; P < 0.001). The viral load levels did not differ between the diagnosed and missed patients, but missed patients more frequently presented without diarrhea (20% versus 4%; P < 0.07). The newly admitted missed NoV cases with GE underwent more diagnostic imaging (24% versus 4%; P < 0.01) and tended to be hospitalized longer. When missed-NoV patients were included, the number of nosocomial clusters doubled and missed patients were index cases in 5 of the 6 clusters. These data indicate that NoV infections are frequently missed despite routine laboratory testing and demonstrate that underdiagnosis of NoV patients is associated with costly abdominal imaging and nosocomial clustering. Awareness of NoV infection in adult patients and education about the importance of viral GE should be increased. Copyright

A case of rickettsialpox in Northern Europe (Article)

2012-03-01T00:00:00Z

We report the first case of rickettsialpox caused by Rickettsia akari in the Netherlands. The diagnosis was suspected based on clinical grounds and was confirmed by Western blot analysis with cross-adsorption. Because the arthropod vector (Liponyssoides sanguineus) is ubiquitous, we suspect that the disease is under-diagnosed in non-endemic areas.

Oseltamivir-resistant pandemic A(H1N1) 2009 influenza viruses detected through enhanced surveillance in the Netherlands, 2009-2010 (Article)

2011-10-01T00:00:00Z

Enhanced surveillance of infections due to the pandemic A(H1N1) influenza virus, which included monitoring for antiviral resistance, was carried out in the Netherlands from late April 2009 through late May 2010. More than 1100 instances of infection with the pandemic A(H1N1) influenza virus from 2009 and 2010 [A(H1N1) 2009] distributed across this period were analyzed. Of these, 19 cases of oseltamivir-resistant virus harboring the H275Y mutation in the neuraminidase (NA) were detected. The mean 50% inhibitory concentration (IC50) levels for oseltamivir- and zanamivir-susceptible A(H1N1) 2009 viruses were 1.4-fold and 2-fold, respectively, lower than for the seasonal A(H1N1) influenza viruses from 2007/2008; for oseltamivir-resistant A(H1N1) 2009 virus the IC50was 2.9-fold lower. Eighteen of the 19 patients with oseltamivir-resistant virus showed prolonged shedding of the virus and developed resistance while on oseltamivir therapy. Sixteen of these 18 patients had an immunodeficiency, of whom 11 had a hematologic disorder. The two other patients had another underlying disease. Six of the patients who had an underlying disease died; of these, five had received cytostatic or immunosuppressive therapy. No indications for onward transmission of resistant viruses were found. This study showed that the main association for the emergence of cases of oseltamivir-resistant A(H1N1) 2009 virus was receiving antiviral therapy and having drug-induced immunosuppression or an hematologic disorder. Except for a single case of a resistant virus not linked to oseltamivir therapy, the absence of detection of resistant variants in community specimens and in specimens from contacts of cases with resistant virus suggested that the spread of resistant A(H1N1) 2009 virus was limited. Containment may have been the cumulative result of impaired NA function, successful isolation of the patients, and prophylactic measures to limit exposure.

Evaluation of the antiviral response to zanamivir administered intravenously for treatment of critically ill patients with pandemic influenza A (H1N1) infection (Article)

2011-09-01T00:00:00Z

A retrospective nationwide study on the use of intravenous (IV) zanamivir in patients receiving intensive care who were pretreated with oseltamivir in the Netherlands was performed. In 6 of 13 patients with a sustained reduction of the viral load, the median time to start IV zanamivir was 9 days (range, 4-11 days) compared with 14 days (range, 6-21 days) in 7 patients without viral load reduction (P = .052). Viral load response did not influence mortality. We conclude that IV zanamivir as late add-on therapy has limited effectiveness. The effect of an immediate start with IV zanamivir monotherapy or in combination with other drugs need to be evaluated.

A comparison of two assays for quantification of Hepatitis B surface Antigen in patients with chronic hepatitis B (Article)

2011-07-01T00:00:00Z

Background and objectives: Serum Hepatitis B surface Antigen (HBsAg) levels correlate with hepatitis B virus intrahepatic covalently closed circular DNA and may predict response to treatment. Currently, 2 commercial platforms are available for HBsAg quantification in clinical practice, the Architect HBsAg QT and the Elecsys HBsAg. We aimed to directly compare the results of these assays. Study design: HBsAg levels were measured in 1427 serum samples from HBeAg-positive chronic hepatitis B patients who participated in a randomized trial of peginterferon alfa-2b ± lamivudine. Samples were extracted from our serum bank, thawed, and subsequently analysed for HBsAg levels using both assays. Results: Of 1427 samples, 242 (17%) were taken before and 1185 during the treatment phase of the study. Distribution of HBV genotypes was 447 (31%) genotype A, 125 (9%) B, 210 (15%) C and 534 (37%) D. Correlation between Architect and Elecsys results was high (r = 0.96, p< 0.001). By Bland-Altman analysis, agreement between the two assays was close (mean difference between Architect and Elecsys: -0.01. log. IU/mL, 95% CI: -0.55-0.52. log. IU/mL), also when analysed separately for HBV genotypes A-D. Additionally, the performance of our recently published stopping rule for HBeAg-positive patients treated with peginterferon was comparable: the negative predictive values were 96% and 98% for Elecsys and Architect, respectively. Conclusions: There is a high correlation and close agreement between quantitative HBsAg measurements conducted with the Architect and the Elecsys. Clinical prediction rules derived from data from one platform can be applied on the other; both can therefore be used in clinical practice.

Quantification of viral DNA and liver enzymes in plasma improves early diagnosis and management of herpes simplex virus hepatitis (Article)

2011-04-01T00:00:00Z

Herpes simplex virus (HSV) hepatitis is a rare and potential life-threatening disease. The diagnosis of HSV hepatitis is hampered by its indifferent clinical presentation, which necessitates confirmatory laboratory data to identify HSV in the affected liver. However, liver biopsies are often contraindicated in the context of coagulopathy, are prone to sampling errors and have low sensitivity in mild HSV hepatitis cases. There is an unmet need for less invasive diagnostic tools. The diagnostic and therapeutic value of HSV DNA load and liver enzyme level kinetics was determined in five patients with HSV hepatitis and twenty disease controls with HSV-DNAemia without hepatitis. At time of hospitalization, patients with HSV hepatitis had a higher median (± interquartile range) HSV DNA load (6.0 × 106± 1.2 × 109) compared to disease controls (171 ± 2845). Viral DNA load correlated with liver transaminase levels and disease severity. Antiviral treatment led to rapid decline of HSV DNA load and improvement of liver function of patients with HSV hepatitis. The data advocate the prompt and consecutive quantification of the HSV DNA load and liver enzyme levels in plasma of patients suspected of HSV hepatitis as well as those under antiviral treatment.

Using molecular epidemiology to trace transmission of nosocomial norovirus infection (Article)

2011-02-01T00:00:00Z

Nosocomial norovirus (NoV) infection is common and may lead to complications in vulnerable hospitalized patients. Understanding sources and modes of transmission of noroviruses within health care settings will support the design of evidence-based strategies for reducing introduction and further spread. We sequenced a highly variable segment of the genome to identify possible clusters in patients with and without acute gastroenteritis who were hospitalized in the period 2002-2007. Admission and sampling dates were used to separate patients with nosocomial infection from those without nosocomial infection. Epidemiological clustering retrieved 22 clusters, defined as ≥2 patients with nosocomial infection on the same ward within 5 days. In total, 264 patients (of 2,458 tested) were diagnosed with NoV infection, and 61% of the patient strains could be genotyped. Of those, 51% (n = 82) belonged to GII.4, 34% (n = 54) belonged to GII.3, and 15% (n = 24) belonged to other genotypes (GI.6B, GII.17, GII.7, and GII.2). In children's wards, GII.3 strains were associated with nosocomial spread more often than other viruses were, whereas in adults this was the case for GII.4 strains. Sequence alignment recognized 11 new clusters based on identical P2 domains (4 GII.3 and 7 GII.4 clusters), involving patients in different wards. This increased the total number of recognized clusters by 50%. Five of these clusters involved at least one outpatient, providing a possible target for improvement of infection control. We concluded that the use of sequence-based typing should be considered for identifying hidden nosocomial clusters of NoV infections within health care settings.

Chronic shedders as reservoir for nosocomial transmission of norovirus (Article)

2010-11-01T00:00:00Z

Norovirus (NoV) infection in immunocompromised patients may lead to prolonged norovirus shedding. Here, we demonstrate the involvement of three chronic shedders in hospital outbreaks. Combined epidemiological and molecular evidence suggests that in one case, NoV transmission occurred at least 17 days after the first diagnosis.

BK virus nephropathy in an immunodeficient patient with chronic lymphocytic leukemia (Article)

2009-08-01T00:00:00Z

Background: BK virus, genus polyomavirus, is known as an important cause of nephropathy (BKVN) in renal transplant patients. Cases of BKVN in native kidneys are rare. Objectives: To report a case of BKVN in a patient with chronic lymphocytic leukemia (CLL) and to examine viral and immune parameters. Study design: Quantitative BK virus DNA in plasma and relevant immune parameters were recorded in one CLL patient with BKVN and ten consecutive CLL patients without BKVN. Results: BKVN in the native kidneys of a CLL patient was histologically confirmed. The presence of BKVN correlated with immunologic parameters as well as factors known to cause renal tissue injury. BK viral load levels in the patient steadily increased and exceeded those of the control CLL patients. Conclusions: The results document a pathogenic role for BK virus in native kidneys of immuno-compromised CLL patients and indicate a role for quantitative BK virus DNA detection for early management of BKVN in native kidneys.

Norovirus in a Dutch tertiary care hospital (2002-2007): frequent nosocomial transmission and dominance of GIIb strains in young children (Article)

2009-03-01T00:00:00Z

We report a retrospective analysis of norovirus (NoV) infections occurring in patients of a tertiary care hospital during five winter seasons (2002/03 to 2006/07). Data were compared with national surveillance data and with corresponding data for rotavirus. Between July 2002 and June 2007, faecal specimens from 221 (9.0%) of 2458 hospital patients with diarrhoea tested positive for NoV. The incidence in children varied from 2.52 per 1000 admissions in 2004/05 (when testing began to be performed routinely) to 11.9 per 1000 admissions in 2006/07, while the incidence in adults remained stable (mean: 1.49 per 1000 admissions). Two genotypes predominated during the study period: GIIb strains occurred mainly in children below the age of two-and-a-half years [odds ratio (OR): 14.7; P < 0.0001] whereas GII.4 strains affected all age groups. Compared with rotavirus infections, NoV infections in children were more often hospital-acquired (59% vs 39%, OR: 2.29; P < 0.01). Among these cases we identified 22 clusters of NoV infection among inpatients. Twelve of 53 patients from whom follow-up samples were available demonstrated long-term virus shedding. We report a dynamic pattern of sporadic NoV infections in large hospitals, with frequent nosocomial transmission and with the predominance of GIIb-related strains in children. Effective prevention strategies are required to reduce the impact of sporadic NoV infection in vulnerable patients.

High prevalence of prolonged norovirus shedding and illness among hospitalized patients: A model for in vivo molecular evolution (Article)

2008-10-01T00:00:00Z

During a 2-year survey in an academic hospital, 8 (8.4%) of all norovirus (NoV)-positive patients showed prolonged norovirus illness and shedding (duration, 21-182 days). All patients had underlying illnesses, resulting in some level of immunodeficiency in 5. Four patients were admitted to the hospital with gastroenteritis, 2 acquired norovirus while hospitalized, and 2 were outpatients. Genotypes GII.4 and GIIb-GII.3 were found. Reinfection occurred in 3 patients. Full capsid sequences were determined from strains detected in sequentially collected stool specimens to study evolution. The greatest number of amino acid mutations in a given patient was 11; they were detected in NoV isolates recovered over a 119-day period and were mapped to positions at or near putative antigenic sites. In the patient with most severe immune dysfunction, only 5 amino acids mutated over 182 days, suggesting immune-driven selection. The severe impact on patients and hospitals and the potential role of prolonged shedders as a reservoir for viral antigenic variants lead us to stress the importance of confinement of outbreaks of NoV infection that occur in hospitals.

The value of Chlamydia trachomatis-specific IgG antibody testing and hysterosalpingography for predicting tubal pathology and occurrence of pregnancy (Article)

2007-07-01T00:00:00Z

We assessed two diagnostic methods, Chlamydia trachomatis-specific IgG and hysterosalpingography (HSG), as a screening test for the likelihood of tubal damage or occurrence of pregnancy before laparoscopy in 178 subfertile women who were randomly assigned to HSG followed by laparoscopy or immediate laparoscopy. The diagnostic accuracy and prognostic value of both C. trachomatis-specific IgG antibody testing and HSG are comparable but show poor performance.