A.A. van der Eijk

Reduced risk of relapse after long-term nucleos(t)ide analogue consolidation therapy for chronic hepatitis B

Before stopping nucleos(t)ide analogue (NA) treatment in chronic hepatitis B (CHB), 6–12 months of consolidation therapy is recommended.

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

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.

Middle east respiratory syndrome coronavirus (MERS-CoV) infections in two returning travellers in the Netherlands, May 2014

Two patients, returning to the Netherlands from pilgrimage in Medina and Mecca, Kingdom of Saudi Arabia, were diagnosed with Middle East respiratory syndrome coronavirus (MERS-CoV) infection in May 2014. The source and mode of transmission have not yet been determined. Hospital-acquired infection and community-acquired infection are both possible.

Viral dynamics during tenofovir therapy in patients infected with lamivudine-resistant hepatitis B virus mutants

Summary.  Tenofovir, an antihuman immunodeficiency virus (HIV) drug, has activity against lamivudine‐resistant hepatitis B virus (HBV) mutants. To describe the efficacy of tenofovir in patients with lamivudine‐resistant hepatitis B we applied two investigative approaches based on mathematical models of viral dynamics: the individual nonlinear fitting and the mixed‐effect group fitting approaches.

Human bocavirus infection as a cause of severe acute respiratory tract infection in children

Abstract In 2005 human bocavirus (HBoV) was discovered in respiratory tract samples of children. The role of HBoV as the single causative agent for respiratory tract infections remains unclear. Detection of HBoV in children with respiratory disease is frequently in combination with other viruses or bacteria. We set up an algorithm to study whether HBoV alone can cause severe acute respiratory tract infection (SARI) in children. The algorithm was developed to exclude cases with no other likely cause than HBoV for the need for admission to the paediatric intensive care unit (PICU) with SARI. We searched for other viruses by next-generation sequencing (NGS) in these cases and studied their HBoV viral loads. To benchmark our algorithm, the same was applied to respiratory syncytial virus (RSV)-positive patients. From our total group of 990 patients who tested positive for a respiratory virus by means of RT-PCR, HBoV and RSV were detected in 178 and 366 children admitted to our hospital. Forty-nine HBoV-positive patients and 72 RSV-positive patients were admitted to the PICU. We found seven single HBoV-infected cases with SARI admitted to PICU (7/49, 14%). They had no other detectable virus by NGS. They had much higher HBoV loads than other patients positive for HBoV. We identified 14 RSV-infected SARI patients with a single RSV infection (14/72, 19%). We conclude that our study provides strong support that HBoV can cause SARI in children in the absence of viral and bacterial co-infections.

Rapid Genotyping of Cytomegalovirus in Dried Blood Spots by Multiplex Real-Time PCR Assays Targeting the Envelope Glycoprotein gB and gH Genes

ABSTRACT Genotyping of cytomegalovirus (CMV) is useful to examine potential differences in the pathogenicity of strains and to demonstrate coinfection with multiple strains involved in CMV disease in adults and congenitally infected newborns. Studies on genotyping of CMV in dried blood spots (DBS) are rare and have been hampered by the small amount of dried blood available. In this study, two multiplex real-time PCR assays for rapid gB and gH genotyping of CMV in DBS were developed. Validation of the assays with 39 CMV-positive plasma samples of transplant recipients and 21 urine specimens of congenitally infected newborns was successful in genotyping 100% of the samples, with gB1 and gB3 being the most prevalent genotypes. Multiple gB and gH genotypes were detected in 36% and 33% of the plasma samples, respectively. One urine sample from a newborn with symptomatic congenital CMV was positive for gB1 and gB2. DBS of congenitally infected newborns (n = 41) were tested using 9 μl of dried blood, and genotypes were detected in 81% (gB) and 73% (gH) of the samples, with gB3 being the most prevalent genotype. No clear association of specific genotypes with clinical outcome was observed. In conclusion, the CMV gB and gH PCR assays were found to be rapid, sensitive for detecting mixed infections, and suitable for direct usage on DBS. These assays are efficient tools for genotyping of CMV in DBS of congenitally infected newborns.

Prolonged antiviral therapy for hepatitis B virus-infected health care workers: A feasible option to prevent work restriction without jeopardizing patient safety

Summary.  To prevent transmission of hepatitis B virus (HBV) from health care workers (HCWs) to patients, highly viraemic HCWs are often advised to restrict performing exposure prone procedures (EPPs). To prevent loss of highly qualified medical personnel and simultaneously minimize transmission risk to patients, we offered highly viraemic HCWs antiviral therapy and evaluated the effects of this strategy. Eighteen chronic HBV‐infected HCWs have been monitored every 3–6 months for a median period of 5.6 years (range 1.1–12.5 years). Antiviral therapy was offered if HBV DNA was above 105 copies/mL and EPPs were performed or active liver disease was present. Median HBV DNA levels, the percentage of days with HBV DNA above 103, 104 and 105 copies/mL, and reduction of HBV DNA during antiviral treatment have been analysed for hepatitis B e antigen (HBeAg)‐positive and HBeAg‐negative HCWs separately. Prolonged viral suppression was achieved in both HBeAg‐positive, as well as HBeAg‐negative HCWs. In HBeAg‐negative HCWs treatment with interferon or lamivudine maintained HBV DNA levels below 105 copies/mL. For HBeAg‐positive HCWs continuous treatment with tenofovir or entecavir was essential for reaching low viraemia persistently. In 2004, median HBV DNA levels in both HBeAg‐negative and HBeAg‐positive HCWs were below 103 copies/mL and all HCWs executed their professional work full‐range. For both HBeAg‐positive and HBeAg‐negative HCWs, antiviral treatment is effective in persistent suppression of virus levels below 105 copies/mL. This observation supports antiviral therapy as a viable management option instead of work restriction, with the provision of regular expert monitoring including quantification of HBV DNA.

Hepatitis E prevalence among HIV infected patients with elevated liver enzymes in the Netherlands.

BACKGROUND In recent years chronic hepatitis E virus (HEV) infections have been reported in immunosuppressed patients, including HIV-positive patients with low CD4 cell counts. Because of delayed anti-HEV seroconversion in patients with CD4 cell count<200 cells/ml it is difficult to draw firm conclusions on HEV-seroprevalence in a population of HIV positive patients. OBJECTIVES To determine the HEV seroprevalence in a population of HIV infected patients. STUDY DESIGN We retrospectively analysed the HEV prevalence in a population of 256 HIV infected patients with liver enzyme elevations (LEEs), using HEV specific antibody testing and HEV-RNA detection. RESULTS Within this cohort we observed a HEV-seroprevalence of 11.7%, without any anti-HEV IgM positive or HEV-RNA positive cases. HEV seropositivity was equally prevalent among different CD4(+) cell count groups. CONCLUSION Although HIV infected patients in the Netherlands are at risk of acquiring HEV, the number of acute infections is low and no chronic cases were found.

Doctor-to-patient transmission of Hepatitis B virus: the potential of antiviral therapy for prevention

Hepatitis B virus (HBV)-infected health-care workers (HCWs) have infected patients during medical procedures. In many countries HBV-infected HCWs are restricted in performing exposure prone procedures based on either HBeAg status or serum HBV DNA level. To prevent loss of skilled HCWs and to minimize transmission risk, highly viraemic HCWs can be offered antiviral therapy. Nucleoside analogues have proven to be effective in reducing transmission of HIV and HBV in the setting of vertical mother-to-infant transmission. Following the same rationale, suppression of viral load in HBV-infected HCWs could minimize the risk of doctor-to-patient transmission to such an extent that job modifications are no longer indicated. To limit the risk of drug resistance, the use of combination therapy is advocated. We describe two chronic HBV-infected HCWs treated with antiviral therapy, eventually leading to well-tolerated and highly effective combination therapy with lamivudine and tenofovir, with continuation of medical practice.

Hepatitis B virus (HBV) DNA levels and the management of HBV-infected health care workers

Summary.  Different guidelines exist for the management of hepatitis B virus (HBV)‐infected health care workers (HCWs). Various HBV DNA levels are used as a cutoff level to determine whether an HBV‐infected HCW is allowed to perform exposure‐prone procedures (EPPs) or not. In this paper we discuss the factors that determine HBV DNA levels and the implications of different HBV DNA cutoff levels for EPP performing HCWs. If the level of HBV DNA in the serum of HCWs is used to determine acceptability for the conduct of EPPs, it is necessary to take into account the variability in time of HBV DNA levels in HBV carriers and the reliability and reproducibility of the molecular diagnostic test involved. The issue of standardization has to be addressed, before a universal, maximum level of viraemia for EPP performing HCWs can be introduced.