"Trivalent influenza vaccination of healthy adults 3 years after the onset of swine-origin H1N1 pandemic: restricted immunogenicity of the new A/H1N1v constituent?".

Influenza vaccination is advised annually to reduce the burden of influenza disease. For sufficient vaccine campaigns also a continuous adoption of influenza vaccines are necessary, due to particularly high genetic variability of influenza A virus. Therefore, we evaluate the effectiveness of the trivalent influenza vaccine 2010/2011, against influenza A (H1N1, H3N2) and influenza B. Immune response was investigated in paired sera from 92 healthcare workers with the hemagglutination inhibition assay (HI). Protective antibody levels (HI titer ≥40) were found after vaccination for influenza A/California/07/2009(H1N1): 84.71 % [GMT: 115.34]; for influenza A/Perth/16/2009(H3N2): 94.94 % [GMT: 268.47] and for influenza B/Brisbane/60/2008: 96.20 % [GMT: 176.83]; matching with the currently circulating virus strains. However, the highest seroprevalence rate was found against influenza B; pre- and post-vaccination titers as well, which may be due to comparatively high virus preservation. Remarkable, lowest seropositivity was seen against H1N1. Despite the significant titer rise, sufficient H1N1 herd immunity was still not achieved. It can be assumed that a high influenza A herd immunity may be a requirement for a successful booster vaccination.

[Measles: immunity and vaccination status in Greater Frankfurt on the Main]. / Masern: Immunität und Impfstatus im Grossraum Frankfurt am Main.

BACKGROUND AND OBJECTIVE: The elimination of measles is a goal of the WHO which has not been achieved in Europe yet. As measles is a vaccine-preventable disease and can be eliminated by immunization the Standing Committee on Vaccination (STIKO) has updated the recommendation of measles vaccination. The goal of this study was to evaluate the immune status by serological testing and by raising immunisation status. METHODS: Antibody-testing from the routine diagnostic of the Institute of Medical Virology (Frankfurt/Main) for patients, health care workers and medical students was investigated retrospectively. RESULTS: Overall all significant increase in seropositivity was shown from 64.8 to 86.2 %. Nevertheless immunity gaps still exist in population, especially in persons under 19 years of age. In 1999 80.7 % of the 5-9 year age group and 75.3 % of the 10-19 year age group were seropositive. In 2009 the percentage in these age groups has decreased to 68.2 % and 71.1 % respectively. By obtaining the immunity status of 230 travellers at our vaccination centre immunity gaps have been recognised as well. Only 29.6 % were completely immunized (at least two vaccination). 54.4 % have been vaccinated incomplete and in 16.1 % vaccination status was unknown. CONCLUSION: Our results indicated that measles immunization status and seroprevalence are still not sufficient to achieve the elimination of measles.

H1N1v at a seroepidemiological glance: is the nightmare over?

When the second wave of pandemic influenza A H1N1v 2009 (H1N1v) emerged in the winter of 2010/2011, public health authorities were afraid of dangerous implications and severe clinical courses again. As further H1N1v waves might appear, achievement of sufficient herd immunity is a matter of urgency. The objective of this study was to determine the seroprevalence of antibodies against H1N1v by hemagglutination-inhibition test (HI) after the second wave. We compared our recent findings with our data obtained after the first pandemic in 2009/2010. Between March and May 2011 we collected serum samples from 600 persons aged 1 to 84 years admitted to University Hospital Frankfurt/Main and analysed the titres of anti-H1N1v by HI. The overall seroprevalence of anti-H1N1v has risen from 36.9% (95% confidence interval (95%CI), 33-41) in unvaccinated persons after the first wave to 57.3% (95%CI, 53.1-61.2) in vaccinated and unvaccinated. The highest rate of seropositivity was detected in the age group of 10-19 years (66%; 95%CI, 55.8-75.2), whereas the lowest was found in the age group 40-59 years (51%; 95%CI, 40.8-61.1). Although seroprevalence has significantly increased, sufficient herd immunity is still not achieved. Therefore, general vaccination programs have to be propagated continuously by public health authorities.

[Comparison of seasonal influenza vaccines: composition and properties]. / Saisonale Influenza-Impfstoffe: Zusammensetzung und Eigenschaften.

The influenza virus isolation in embryonated chicken eggs was possible early in 1930er years and allowed the influenza vaccine production. Most influenza vaccines were derived from this, but actually new virus cell culture methods are established. For better tolerability, influenza vaccines include only antigen proportions (split- and subunit vaccines) but with the disadvantage of minor vaccine efficacy. This was compared with the addition of adjuvants. Aluminium salts are used for many decades and still in use to enhance the effect of vaccines. New formulations are MF59, AS03, AS04 or toll- like receptor-agonists. Also virosomal formulations and "ISCOMs"(Immune Stimulating Complexes) are newly designed and compromises enhanced immune reactions. Actually a broad range of various influenza vaccines exist and are available for a very different group of patients (which depends on physical conditions, age, immune status or allergies).

Assessment of mumps virus-specific antibodies by different serological assays: which test correlates best with mumps immunity?

Mumps is one of the vaccine-preventable childhood diseases and it has not yet been eradicated in Germany. This raises the question as to whether the available mumps vaccines are effective enough to prevent mumps and which antibody test system allows the authentic assigning of mumps-specific immunity. In an attempt to answer this question, we analysed 227 sera samples from medical students of the University Hospital Frankfurt/Main, Germany, using different test systems: indirect immune fluorescence, neutralisation assay, routine ELISA and newly developed immunoassays, which contain the mumps nucleoprotein and the wild-type strain Enders ATCC VR106, respectively. Mumps vaccination coverage of the screened collective amounted to 75.1%, which differs notably from the detected mumps-specific seropositivity rates in the literature (range 53.3% to 82.4%). In contrast, a small group of unvaccinated students had much higher seropositivity rates. Of course, assigned vaccination coverage and calculated seropositivity rates are not effective enough to interrupt the transmission of the mumps virus. The often-occurring mumps outbreaks, some in highly vaccinated populations, may not always demonstrate vaccine failure. The investigation of newly developed test systems and the occurrence of different mumps virus genotypes should also be considered.

Limited prevalence of influenza A/H1N1v antibodies: footprints of the pandemic of 2010.

BACKGROUND: The intention of our investigation was to determine the seroprevalence of H1N1v antibodies after a pandemic by the haemagglutination inhibition (HI) test. We included the serum samples of adults who had not received vaccination against H1N1v. By means of serological footprints, the spread of infection can be investigated. MATERIALS AND METHODS: Between December 2009 and May 2010, we collected 233 serum samples from healthy people aged 1-72 years and analysed the titres of H1N1v antibodies by the use of the HI test. RESULTS: After the pandemic, a seroprevalence of 36.9% was observed. The highest rate of seropositivity was detected in the age group of 10-19 years (60%) and the lowest rate was found in the age group of 30-39 years (22%). The seroprevalence of H1N1v antibodies in females exceeded the rate of positive men (41.5 vs. 31.8%). Almost 70% of the influenza A/H1N1v infections were passed inapparently.

Seroepidemiology of parvovirus B19 in the Frankfurt am Main area, Germany: evaluation of risk factors.

BACKGROUND: Parvovirus B 19 is a virus that is distributed by respiratory droplets. It is known to be an initiator of erythema infectiosum (children's fifth disease), with erythroblasts being the target cells of infection. In case of vertically transmission, hydrops fetalis has been documented. OBJECTIVE: Parvovirus B19 seroprevalence was investigated in serum samples routinely collected from patients who had been admitted to the University Hospital in Frankfurt a. M., Germany. Patients were classified in different groups in order to analyze parovirus B19 seroprevalences in terms of risk factors. MATERIALS AND METHODS: Between June 2007 and March 2010, a total of 2,197 serum samples were analyzed for parvovirus B19-immunoglobulin G using an enzyme-linked immunosorbent assay. The study population included six groups of patients, namely, patients suffering from haemophilia, malignant disease, immunodeficiency diseases, common gynecological ailments, pregnant women and children with malignant diseases. RESULTS: Of the 2,197 serum samples, 1,383 contained antibodies to parvovirus B19 (62.9%). The overall seroprevalence in adults (20 to ≥60 years of age) was 71%. Gradually rising prevalences were recorded in children/adolescents with increasing age. We found a positive serostatus in 54.9% of adult patients with malignant disease, in 64.2% of patients with haemophilia (1 to ≥60 years), in 66.7% of patients under immunosuppression with various drugs (1 to ≥60 years) and in 41.7% of oncological patients aged 1-19 years. Of the pregnant women (aged 15-49 years), 71.1% were seropositive. CONCLUSION: The seroprevalence of parvovirus B19 in patients admitted to the University Hospital in Frankfurt a.M. was, on average, lower than that among the general population in Germany. Infection among patients in specific risk groups did not spread more than that in age-matched non-selected patients, with the exception of the group of immunocompromised patients.

Influenza vaccination compliance among health care workers in a German university hospital.

BACKGROUND: Since 1988, the Standing Committee on Vaccination (STIKO) at the Robert Koch-Institute, Berlin, has explicitly recommended that health-care workers (HCWs) should be vaccinated against seasonal influenza. However, acceptance of the influenza vaccination by medical personnel is low. METHODS: This study analyzes factors associated with the compliance of HCWs with the seasonal influenza vaccination on the basis of three different anonymized questionnaires during two consecutive influenza seasons: 2006/2007 and 2007/2008. The questionnaires covered details of demographics, frequency of previous vaccinations, reasons for accepting or declining the vaccination, and the HCW's knowledge of the influenza vaccine and influenza itself. RESULTS: Our study showed that physicians were significantly more likely to have been vaccinated than nurses (38.8% vs 17.4%; p < 0.0001). The main reasons for noncompliance included: supposition of a low risk of infection, fear of side effects, the belief that the influenza vaccine might trigger the influenza virus infection, and scepticism about the effectiveness of the influenza vaccination. CONCLUSION: Our findings confirm the importance of a comprehensive approach to the vaccination, ensuring that HCWs are correctly informed about the vaccine and that it is convenient to receive it.

[Influenza: acceptance of vaccination by healthcare personnel. Evaluation of the influenza season 2006/2007]. / Influenza: Akzeptanz der Schutzimpfung bei medizinischem Personal. Auswertung zur Influenzasaison 2006/2007.

BACKGROUND AND OBJECTIVE: Since 1988 the recommendations of the Standing Committee on Vaccination (STIKO) at the Robert Koch Institute has explicitly designated healthcare workers (HCW) as persons that should be vaccinated against influenza. However, the acceptance rate of influenza vaccination within medical personnel is low. This account describes reasons why the vaccination rate remains inadequate and how it could be improved. METHODS: At the University Hospital Frankfurt an anonymized questionnaire regarding the attitude towards influenza vaccination was distributed in the course of a vaccination campaign in 2006/2007. 1,052 healthcare workers among 4,080 healthcare workers (2,715 females/ [66.5%]; 1,365 males [ 33.5%] were vaccinated against influenza (35.8%), 628 females and 419 males, while gender was not recorded for five. Most of the participants (76.2%) were between 20 and 49 years old. RESULTS: An extensive information campaign achieved an increase in the influenza vaccination rate. Nevertheless significant vaccination gaps still exist. A mere 25.8% of personnel participated in the influenza vaccination campaign. CONCLUSION: In spite of an extensive vaccination campaign and a significantly increased vaccination rate of the personnel (3.5% in 2001/2002; 25.8% in 2006/2007), the acceptance of influenza vaccination remains low. Long-term measures are required to obtain better rates for preventive vaccine protection against influenza.

Loss of varicella zoster virus antibodies despite detectable cell mediated immunity after vaccination.

BACKGROUND: Vaccination of children against VZV has been included in the recommendations of the "permanent committee of vaccination" (STIKO; Ständige Impfkommission of the Robert Koch Institute, Berlin, Germany) in July 2004. Due to this recommendation the medical practitioner and the laboratories will be confronted with the problem of serologic non-responders or loss of humoral immunity more frequently. PATIENTS AND METHODS: Here we report the case of a Varicella Zoster Virus (VZV) vaccinee, who lost detectable VZV antibodies although she had a persisting VZV specific CD4 cellular immune response. We compare these parameters to the VZV specific CD4 T cell responses of VZV seronegative and seropositive healthy persons, as well as patients with VZV disease. RESULTS: VZV specific CD4 frequencies of VZV antibody seronegative persons remained on the average below 0.1% (median 0.04%, +/- SD 0.03, range 0.01-0.08%) and were significantly lower than VZV specific frequencies of seropositive healthy persons (median 0.3%, +/- SD 0.24, range 0.06-0.81%; Mann-Whitney U-test p = 0.001). The samples of patients with VZV associated disease showed an even higher median level of VZV specific CD4 cell response than the VZV seropositive healthy persons (median 1.04%, +/- SD 1.06, range 0.51-2.92%, Mann-Whitney U-test p = 0.008). The VZV specific immune response of the health care worker directly after vaccination was comparable to the VZV specific immunity in VZV seropositive healthy adults. Despite serological reconversion 1.5 years later the VZV specific CD4 response still remained measurable and positive. CONCLUSION: The new general VZV vaccination recommendation for children in Germany will probably increase the number of persons that will be seronegative after vaccination. To gain more information concerning the absence of seroconversion or the loss of immunity, it will be necessary to focus future post-VZV vaccination immunity studies not only on serologic testing but also on the measuring of the cell mediated immunity.

[Is avian influenza a risk for humans?]. / Ist die Vogelgrippe eine Gefahr für den Menschen?

Avian influenza is an infectious disease of birds, caused by type A strains of the influenza virus. The disease, which was first identified in Italy more than 100 years ago, occurs worldwide. Avian influenza viruses are mainly distributed by migratory birds. Different mammals like swine, horse and finally humans are susceptible for avian influenza viruses. The high possibility of genomic changes like gene shift and drift is caused by the segmented RNA genome. During the avian flu outbreak in East Asia at the end of 2003 the virus also killed several humans in Vietnam and Thailand. That avian influenza could also infect humans has been known since 1997. The H5N1 flu outbreak seemed successfully controlled, but currently new cases in poultry and humans in Vietnam, Thailand, China and Indonesia are recognized. Also another avian influenza A strain type H9N2 was prevalent in chickens of local markets in Hong Kong. Because of the natural virus reservoir like wild and/ or domesticated ducks and others, actually there is little chance of eradicating avian influenza. Furthermore the virus could mutate and jump to humans with the threat of a global influenza pandemic.

Viral zoonoses - a threat under control?

Despite intensive research and considerable effort to eradicate infectious diseases, modern medicine has failed to control many infectious diseases which have been thought to be easy to overcome with advances in medical science and technology. In fact, infectious diseases remain a dominant feature in public health considerations for the 21st century. Some infectious agents already known to be pathogenic have gained increasing importance in recent decades due to changes in disease patterns. Furthermore, many new, previously unknown infectious agents with a high pathogenic potential have been identified. Nearly all of these emergent disease episodes have involved zoonotic or species-jumping infectious agents. The complex interaction of factors like environmental and ecological changes, social factors, decline of health care, human demographics and behaviour influences the emergence of re-emergence of such diseases. Viruses, especially RNA viruses with their ability to adapt quickly to changing environmental conditions, are among the most prominent examples of emerging pathogens. In this review, we present the important examples of zoonotic viruses and discuss the factors playing a key role in the emergence and resurgence of these diseases.

Laboratory diagnosis of influenza--virology or serology?

Although classical influenza is a clinically typical illness ("unchanging disease due to a changing agent"), laboratory investigations are essential at the beginning of each influenza epidemic. They should confirm suspected influenza cases and exclude "flu-like illnesses" which may be caused by numerous other viral and bacterial agents. Different virological as well as serological methods are available. For early diagnosis of acute influenza virus infections, virus detection using rapid procedures for virus isolation or antigen staining and molecular biological techniques have been developed. The determination of specific antibodies (IgG, IgM) has traditionally been widely used diagnostically. Conventional serological diagnosis is possible by means of the complement fixation and hemagglutination inhibition tests and allows the detection of type- and subtype-specific antibodies, respectively. As part of an automated serology, immunofluorescence test and enzyme-linked immunosorbent assay are the mostly widely available methods. In comparison, virus detection is clearly superior to antibody determination for diagnosis of influenza virus infections. However, antibody testing may be useful as a complementary tool to confirm the diagnosis retrospectively.

The "influenza vaccine"--benefit, risk, costs.

More than 20 million people died during the pandemic 'flu season 1918/1919, the largest influenza pandemic of the 20th century. Since then, influenza A virus infections have been known as a serious cause of morbidity and mortality in the whole world population. Although specific and effective antiviral therapeutics (neuraminidase inhibitors) are available, vaccinating against influenza is the first preventative measure. In Germany, influenza immunization has been yearly recommended by the current vaccination committee of the Robert Koch Institute (STIKO). Vaccinations have a special indication in elderly persons >60 years, patients with chronic diseases and persons with higher risk of influenza infections. In general, inactivated vaccines are well tolerated by recipients. The cost effectiveness of influenza vaccination has been well established. Although the benefit of annual influenza vaccination especially for the elderly and risk groups is beyond doubt, a low acceptance of vaccine recommendations has been noticed in Germany to date.

Travel-acquired dengue infection: clinical spectrum and diagnostic aspects.

BACKGROUND: Dengue fever is increasingly recognized in travelers returning from endemic areas with acute febrile illness; however, its true burden in nonendemic countries is unknown. Only few studies focus on clinical manifestations and serological findings in primarily nonimmune individuals. PATIENTS AND METHODS: We analyzed the epidemiology, clinical manifestations and virological results in patients with imported acute dengue infection who presented at our travel clinic in Frankfurt am Main, Germany, between September 1998 and November 2000. An immunochromatographic test and an immunofluorescence assay were used for antibody testing. RESULTS: Dengue fever was confirmed in 13 patients, thus being the second commonest tropical infection after malaria in patients with fever and a travel history to a tropical country (18 cases per 1,000 patient visits per year). Most patients had only spent a short time abroad, either in South Central or South East Asia or in the Caribbean. CONCLUSION: The clinical features considered typical for dengue were not always present. Antibody assays were typically negative early in the course of disease, with seroconversion occurring only after cessation of clinical symptoms. A high index of suspicion is needed in these patients who often present without typical features of dengue and whose early antibody tests may be negative.

Cross-reactivity in flavivirus serology: new implications of an old finding?

To investigate the influence of pre-existing antibodies against tick-borne encephalitis (TBE) or yellow fever (YF) viruses on dengue virus antibody test results, we examined sera from vaccinees and from individuals with previous TBE virus infection. Distinct IgG antibody cross-reactivity was found in about 15.1% in the YF-vaccinated group and in about 9.5% in the TBE-vaccinated group. Altogether 15 out of a total of 80 samples tested (18.8%) had detectable dengue virus IgG antibody titres. The serum samples from patients with acute TBE virus infection not only had the highest anti-TBE virus antibodies but were also highly cross-reactive against dengue virus antigens. The high cross-reactivity rate of YF and TBE antibody-positive sera in dengue virus antibody assays should be taken into account in the interpretation of laboratory tests for the diagnosis of flavivirus infections and when undertaking seroepidemiological surveys.

[Epidemiological analysis of immunity against vaccine-preventable diseases: rubella, measles, mumps and chickenpox]. / Untersuchungen zur Immunitätslage der impfpräventablen Kinderkrankheiten Röteln, Masern, Mumps und Windpocken.

BACKGROUND AND OBJECTIVE: Measles, mumps, rubella and varicella zoster virus (VZV) infections are regarded as typical diseases of childhood: They are normally clinically mild and result in lifelong immunity. Severe clinical disease is known in immunocompromised patients; rubella virus infections during pregnancy often result in congenital rubella syndrome. All these diseases are preventable by vaccination which is recommended in Germany, recently vaccination against VZV for teenager without immunity since July 2001. In the following study we screened for immunity against the four viruses. PATIENTS AND METHODS: Serum samples were obtained at the Institute of Medical Virology Frankfurt/Main from January 1999 until December 2000. We tested for specific antibodies against measles (n = 915), against mumps (n = 857), against rubella (n = 1886) and against VZV (n = 2291). Seroprevalences were determined in different age groups. RESULTS: Altogether the highest rate of seronegatives is detected in younger children. VZV-seronegativity rates decrease from 74 % to 32 % in younger children. Against rubella also in this age group rate of seronegatives is found in 40 % and less than 10 % by teenagers. From this age group also immunity against rubella is found approximately in 80 % of seropositives. CONCLUSIONS: The following study shows that high seronegative rates are detectable, and here specially against VZV-specific antibodies. For seronegative teenagers, vaccination against VZV is now recommended in Germany. Immunization rates of at least 95 % in childhood would be effective in avoiding severe courses of disease and giving protection in pregnancy.