[An outbreak of respiratory tract infections in an institution: combating Mycoplasma pneumoniae in mentally disabled persons]. / Een uitbraak van Mycoplasma pneumoniae in een instelling voor mensen met een verstandelijke beperking.

BACKGROUND: In October 2013, the Municipal Health Service, Rotterdam, the Netherlands, was notified of an outbreak of Mycoplasma pneumoniae infections in an institution for mentally disabled persons. CASE DESCRIPTION: A total of 58 potential infections were identified, of which 12 were confirmed in the laboratory, 5 with PCR testing on throat swabs, 3 by an increased IgM value in the serum, 2 via IgM seroconversion and 2 with an increased IgG titer in consecutive serum samples. To combat the outbreak, measures were taken in collaboration with the municipal health service. Every patient who coughed with fever or malaise was considered to be potentially infected and immediately treated with antibiotics, with as much cohort nursing as possible. The staff made every effort to explain the more stringent hand and cough hygiene measures to the residents. CONCLUSION: An outbreak of Mycoplasma pneumonia in an institution for mentally disabled persons was controlled through active disease surveillance, treatment of potential cases and hygiene measures.

September through October 2010 multi-centre study in the Netherlands examining laboratory ability to detect enterovirus 68, an emerging respiratory pathogen.

During September and October 2010, the Dutch Public Health Institute detected an enterovirus (EV) 68 (EV68) epidemic in the Netherlands through general practitioner-based surveillance of acute respiratory infections. EV68 shares phenotypic and genotypic properties with human rhinovirus (HRV). Despite increased EV and HRV detections, Dutch clinical laboratories did not identify EV68. To assess the capability of Dutch clinical laboratories to detect EV68, ten laboratories with more than eight detected EV and HRV cases in September and October 2010 provided information about their detection algorithms and testing results for a 2010 Dutch EV68 strain. For EV detection mostly stool specimens (median 49%), respiratory specimens (median 27%) and cerebrospinal fluid (median 22%) were used. For HRV detection only respiratory specimens were used. Except for the Seeplex® RV15ACE EV-specific assay, all EV and 73% of HRV assays, including those of the Public Health Institute, were able to detect EV68. Two-step EV RT-PCR protocols were the most sensitive. Thus, laboratories might have misidentified EV68 as HRV. In addition, EV68 cases might have also been missed because patients with respiratory diseases are usually not tested for EV infection. Therefore, clinical laboratories should include EV detection in the differential diagnosis of patients presenting with respiratory symptoms.

Reciprocal changes of naïve and effector/memory CD8+ T lymphocytes in chronic hepatitis B virus infection.

Persistent viruses, such as cytomegalovirus or human immunodeficiency virus, cause major perturbations of CD8+ T-lymphocyte subpopulations. To test whether chronic infection with hepatitis B virus (HBV) could also be responsible for such modifications, we analyzed the expression of CD27, CD28, CCR7, and perforin in blood CD8+ T lymphocytes. In comparison to healthy subjects and patients recovering from acute hepatitis B, chronic hepatitis B patients showed higher percentages of naïve CD8+ T lymphocytes (CD45RA+CD27+CD28+), and lower percentages of intermediately-differentiated CD27+CD28⁻CD8+ T cells. The late differentiated CD45RA+CD27⁻CD28⁻ subset was also present in a large percentage in some patients, but no statistically significant difference with healthy controls was observed. Removal from the circulation of intermediately-differentiated CD8+ T lymphocytes may occur during chronic HBV infection, favoring the recruitment of naïve cells. This may result in impairment of the generation of functionally-competent memory cells, and an inability to achieve control of HBV replication.

In vitro use of autologous dendritic cells improves detection of T cell responses to hepatitis B virus (HBV) antigens.

T lymphocyte responses to hepatitis B virus (HBV) core antigen (HBcAg) are vigorous and easily detectable in vitro during recovery from acute hepatitis B but significantly weaker in patients with chronic HBV infection. In contrast, T cell responses to hepatitis B surface antigen (HBsAg) are almost undetectable during infection and even in a substantial fraction of subjects receiving vaccination with HBsAg. The aim of this study was to investigate whether the use of dendritic cells (DCs) in an in vitro assay could increase the detection of HBV-specific T cells in these conditions. Autologous monocyte-derived DCs, compared to direct HBsAg addition to the cultures, increased the stimulation of HBs- specific T cells. These were detected in 73% of healthy subjects who had recently received hepatitis B vaccine and in 43% of patients recovering from acute hepatitis B. Likewise, proliferation in response to DC-presented HBcAg was detected in both CD4(+) and CD8(+) T cells from the majority of chronic hepatitis B patients. A longitudinal evaluation of HBc-specific T cell responses during and after a 1-year treatment with pegylated interferon (IFN)-alpha showed that HBc-specific CD4(+) T cell responses had no correlation with sustained virus suppression whereas CD8(+) T cell responses were more frequently detected in patients able to control HBV replication after therapy interruption. The use of autologous DCs as antigen-presenting cells appears applicable to clinically relevant in vitro evaluation of T cell responses, particularly in those conditions characterized by low frequency of circulating antigen-specific cells and suboptimal in vivo activation.

Antiviral treatment with alpha interferon up-regulates CD14 on liver macrophages and its soluble form in patients with chronic hepatitis B.

To investigate whether therapy with alpha interferon (IFN-alpha) induces changes in intrahepatic antigen-presenting cells (APCs), we obtained liver biopsy specimens before, during, and after therapy with IFN-alpha from chronic hepatitis B patients whose viral load had already been reduced by at least 8 weeks of treatment with lamivudine. HLA-DR, CD1a, and CD83 were not modified by the therapy. The intralobular expression of CD68 on Kupffer cells remained stable, denoting no changes in the number of resident macrophages during IFN-alpha treatment. In contrast, CD14 was weakly expressed in the absence of IFN-alpha and was significantly up-regulated during therapy. At the same time, the levels of soluble CD14 and interleukin-10 in plasma increased significantly. In vitro, monocytes maintained in the presence of IFN-alpha differentiated into macrophages or dendritic cells with higher levels of expression of CD14 than that for the control cultures. During therapy with IFN-alpha, T-cell infiltration in the portal spaces was reduced, mainly due to a significant decrease in the number of CD8(+) T cells. These findings show that IFN-alpha is biologically active on APCs in vivo and in vitro and suggest that this newly described regulatory function, together with the already known inhibitory effects on lymphocytes, may cooperate to reduce inflammation and consequent tissue damage in patients with chronic viral hepatitis.

Hepatitis B virus-specific T cell response in chronic hepatitis B patients treated with lamivudine and interferon-alpha.

AIMS: The goal of the present study was to assess the impact combination antiviral therapy has on immune responses in chronic hepatitis B. MATERIALS AND METHODS: T cell responses were studied in 16 chronically hepatitis B virus (HBV)-infected patients treated with sequential, partially overlapping, lamivudine-interferon (IFN)-alpha combination therapy. RESULTS: HBcAg-specific lymphoproliferative response (LPR) was transiently detected in four of five patients who achieved virus suppression (HBV DNA < 10(4) genome equivalents/ml) at end of dual therapy, and then reverted to pre-treatment viral load after therapy discontinuation. In contrast, no significant HBcAg-specific LPR was detected in 8 patients who did not attain profound HBV suppression, as well as in three patients who experienced no HBV DNA rebound after therapy discontinuation. CONCLUSIONS: This pilot study suggests that restored viral replication after pharmacological suppression drives the immune response to HBV in chronically infected patients. Further characterization of the adaptive immunity and its regulatory mechanisms at time of therapy discontinuation appears therefore necessary in controlled trials.