Post-pandemic seroprevalence of pandemic influenza A (H1N1) 2009 infection (swine flu) among children <18 years in Germany.

BACKGROUND: We determined antibodies to the pandemic influenza A (H1N1) 2009 virus in children to assess: the incidence of (H1N1) 2009 infections in the 2009/2010 season in Germany, the proportion of subclinical infections and to compare titers in vaccinated and infected children. METHODOLOGY/PRINCIPAL FINDINGS: Eight pediatric hospitals distributed over Germany prospectively provided sera from in- or outpatients aged 1 to 17 years from April 1(st) to July 31(st) 2010. Vaccination history, recall of infections and sociodemographic factors were ascertained. Antibody titers were measured with a sensitive and specific in-house hemagglutination inhibition test (HIT) and compared to age-matched sera collected during 6 months before the onset of the pandemic in Germany. We analyzed 1420 post-pandemic and 300 pre-pandemic sera. Among unvaccinated children aged 1-4 and 5-17 years the prevalence of HI titers (≥1∶10) was 27.1% (95% CI: 23.5-31.3) and 53.5% (95% CI: 50.9-56.2) compared to 1.7% and 5.5%, respectively, for pre-pandemic sera, accounting for a serologically determined incidence of influenza A (H1N1) 2009 during the season 2009/2010 of 25,4% (95% CI : 19.3-30.5) in children aged 1-4 years and 48.0% (95% CI: 42.6-52.0) in 5-17 year old children. Of children with HI titers ≥1∶10, 25.5% (95% CI: 22.5-28.8) reported no history of any infectious disease since June 2009. Among vaccinated children, 92% (95%-CI: 87.0-96.6) of the 5-17 year old but only 47.8% (95%-CI: 33.5-66.5) of the 1-4 year old children exhibited HI titers against influenza A virus (H1N1) 2009. CONCLUSION: Serologically determined incidence of influenza A (H1N1) 2009 infections in children indicates high infection rates with older children (5-17 years) infected twice as often as younger children. In about a quarter of the children with HI titers after the season 2009/2010 subclinical infections must be assumed. Low HI titers in young children after vaccination with the AS03(B)-adjuvanted split virion vaccine need further scrutiny.

Cellular immunity and active human cytomegalovirus infection in patients with septic shock.

BACKGROUND: Human cytomegalovirus (CMV) is an important opportunistic pathogen after transplantations. In the present study, monitoring of CMV in patients with septic shock was used to discover whether T helper cell type 1 (Th1) cell and natural killer (NK) cell functions interact with CMV reactivation in patients not undergoing immunosuppressive therapy. METHODS: Thirty-eight patients with septic shock were monitored, and the 23 CMV-seropositive patients were included in this prospective study. RESULTS: Seven patients (30.4%) developed an active CMV infection despite the detection of CMV-reactive Th1 cells. After active CMV infection, the frequency of CMV-reactive Th1 cells increased from a median of 0.52% to 5.04% (P=.009). Active CMV infections were terminated without antiviral therapy within 2 weeks. In parallel, the frequency of staphylococcal enterotoxin B (SEB; superantigen)-reactive Th1 cells increased from a median of 1.11% to 8.48% (P=.027). In patients without active CMV infection, the frequency of CMV-reactive (median, 0.39%) and SEB-reactive (median, 1.11%) Th1 cells did not increase. Cytotoxic NK cell activity was persistently suppressed despite the presence of CD56(+)CD16(+) NK cells. Moreover, interleukin-2 application in vitro did not restore NK cell activity. CONCLUSIONS: A proinflammatory immune response may contribute to CMV reactivation in patients with septic shock. Adaptive T cell immunity, more likely than NK cell immunity, may contribute to termination of active CMV infection without antiviral therapy in these patients.

Active cytomegalovirus infection in patients with septic shock.

Cytomegalovirus (CMV) is a pathogen of emerging importance for patients with septic shock. In this prospective study, 25 immunocompetent CMV-seropositive patients with septic shock and an intensive care unit stay of > or =7 days were monitored by using quantitative pp65-antigenemia assay, shell vial culture, and virus isolation. Within 2 weeks, active CMV infection with low-level pp65-antigenemia (median 3 positive/5x10(5) leukocytes) developed in 8 (32%) patients. Infection was controlled within a few weeks (median 26 days) without use of antiviral therapy. Duration of intensive care and mechanical ventilation were significantly prolonged in patients with active CMV infection. CMV reactivation was associated with concomitant herpes simplex virus reactivation (p = 0.004). The association between active CMV infection and increased illness could open new therapeutic options for patients with septic shock. Future interventional studies are required.

Severe graft rejection, increased immunosuppression, and active CMV infection in renal transplantation.

Associations between active cytomegalovirus (CMV) infection, graft rejection, rejection therapy, and clinical signs and symptoms have been shown repeatedly. However, the causes and the sequence of events remain an area of debate. Two hundred twenty five patients with cadaveric renal transplant were included in the present study. Clinical signs and symptoms, and the development of active CMV infections were recorded during the first 3 months after renal transplantation. CMV monitoring by pp65-antigenemia was performed followed by preemptive antiviral therapy. Delayed graft function and severe graft rejection followed by anti T-cell antibody therapy was associated with the development of active CMV infection. In contrast, the induction therapy with anti-T-cell antibodies was not associated with more active CMV infections. Post-transplant morbidity determined by fever, pneumonia, and duration of hospital stay was increased significantly in patients with active CMV infection. However, in times of preemptive antiviral therapy an increased morbidity occurred in association with severe graft rejection and not with active CMV infection alone. In patients with renal transplantation and preemptive antiviral therapy, the morbidity was no more influenced by the CMV serostatus although the prevalence of active CMV infection was obviously different between CMV exposed (D+/R+,D+/R-, D-/R+) and unexposed (D-/R-) patients. Severe graft rejection and increased immunosuppression could stimulate cooperatively active CMV infections whereas immunosuppression alone may not be as effective. Prevention of severe graft rejection may be important to decrease early post-transplant morbidity and also the development of active CMV infections after renal transplantation.

Thrombocytopenia and acute renal failure in Puumala hantavirus infections.

Nephropathia epidemica, caused by Puumala virus (PUUV) infection, is a form of hemorrhagic fever with renal syndrome of variable severity. Early prognostic markers for the severity of renal failure have not been established. We evaluated clinical and laboratory parameters of 15 consecutive patients with acute PUUV infection, which is endemic in the Alb-Danube region, South Germany. Severe renal failure (serum creatinine >620 micromol/L) was observed in seven patients; four required hemodialysis treatment. Low platelet count (<60 x 109/L), but not leukocyte count, C-reactive protein, or other parameters obtained at the initial evaluation, was significantly associated with subsequent severe renal failure (p = 0.004). Maximum serum creatinine was preceded by platelet count nadirs by a median of 4 days. Thrombocytopenia <60 x 109/L appears predictive of a severe course of acute renal failure in nephropathia epidemica, with potential value for risk-adapted clinical disease management.

High variability between results of different in-house tests for cytomegalovirus (CMV) monitoring and a standardized quantitative plasma CMV PCR assay.

A total of 2,718 blood samples were analyzed in five virological laboratories for the presence of cytomegalovirus (CMV) by in-house tests and one standardized plasma PCR assay. Results from in-house tests showed remarkable variability. Detection of CMV pp65 antigen or DNA from cells was more sensitive than that by plasma CMV PCR assay.