Eradication of measles: remaining challenges.

Measles virus (MeV) is an aerosol-borne and one of the most contagious pathogenic viruses known. Almost every MeV infection becomes clinically manifest and can lead to serious and even fatal complications, especially under conditions of malnutrition in developing countries, where still 115,000 to 160,000 patients die from measles every year. There is no specific antiviral treatment. In addition, MeV infections cause long-lasting memory B and T cell impairment, predisposing people susceptible to opportunistic infections for years. A rare, but fatal long-term consequence of measles is subacute sclerosing panencephalitis. Fifteen years ago (2001), WHO has launched a programme to eliminate measles by a worldwide vaccination strategy. This is promising, because MeV is a human-specific morbillivirus (i.e. without relevant animal reservoir), safe and potent vaccine viruses are sufficiently produced since decades for common application, and millions of vaccine doses have been used globally without any indications of safety and efficacy issues. Though the prevalence of wild-type MeV infection has decreased by >90 % in Europe, measles is still not eliminated and has even re-emerged with recurrent outbreaks in developed countries, in which effective vaccination programmes had been installed for decades. Here, we discuss the crucial factors for a worldwide elimination of MeV: (1) efficacy of current vaccines, (2) the extremely high contagiosity of MeV demanding a >95 % vaccination rate based on two doses to avoid primary vaccine failure as well as the installation of catch-up vaccination programmes to fill immunity gaps and to achieve herd immunity, (3) the implications of sporadic cases of secondary vaccine failure, (4) organisation, acceptance and drawbacks of modern vaccination campaigns, (5) waning public attention to measles, but increasing concerns from vaccine-associated adverse reactions in societies with high socio-economic standards and (6) clinical, epidemiological and virological surveillance by the use of modern laboratory diagnostics and reporting systems. By consequent implementation of carefully designed epidemiologic and prophylactic measures, it should be possible to eradicate MeV globally out of mankind, as the closely related morbillivirus of rinderpest could be successfully eliminated out of the cattle on a global scale.

Progress in VZV vaccination? Some concerns.

Since 1995, many countries have been aiming to replace the natural immunity against varicella by a vaccine-induced immunity to protect against varicella and herpes zoster. While the frequency of varicella in childhood has been significantly reduced, in future, herpes zoster morbidity might increase in the elderly due to the weaker immunity post-vaccination and the absence of immunity boosting silent reinfections. In countries, where less than 90 % of children are covered by universal vaccination, varicella zoster virus (VZV) infection is not completely eradicated, but might move from childhood to the age of young adults who suffer from more serious complications. A special VZV vaccine against herpes zoster in adults aged >60 years has proven to be effective in many cases, but not all vaccinees. This might lead to problems regarding the acceptance of vaccination and delay rapid antiviral therapy to prevent the post-zosteric neuralgia. An efficacious-inactivated VZV vaccine to protect immunocompromised patients is still missing. VZV vaccines and vaccination strategies have to be optimised to avoid that the quality of life and cost savings from varicella reduction in childhood are offset by more VZV diseases in adults.

Case report: risk of virus infection after accidental blood inoculation from a multi-infected AIDS patient.

Infections caused by blood-borne viruses such as hepatitis B and C and the human immunodeficiency virus (HIV) are associated commonly with needlestick injuries, especially in a hospital setting. A prospective investigation was conducted on a medical doctor who suffered an accidental needlestick injury during blood collection from a patient with AIDS. The patient's blood contained 195,000 copies of HIV RNA, 1 × 10(6) IU hepatitis C virus (HCV) RNA, and >10(7) copies of parvovirus B19 DNA per 1 ml plasma. It was positive for cytomegalovirus virus and evidence of a resolved hepatitis B virus (HBV) infection was found. HCV viremia was detected in the physician 15 days later and was not resolved by seroconversion after 57 days. HIV infection was not transmitted, possibly because of the immediate use of anti-HIV prophylactic drugs after exposure. Parvovirus B19 infection was presumably prevented by pre-existing specific antibodies in the patient. Considering that many HIV carriers are coinfected with hepatitis B and C viruses, this case report support the knowledge that the risk of HCV transmission from a patient with AIDS is greater than that of HIV.

Recent publications in medical microbiology and immunology: a retrospective.

A look back is done to some clinical and basic research activities recently published in medical microbiology and immunology. The review covers clinical experiences and in vitro experiments to understand the emergency, pathogenicity, epidemic spread, and vaccine-based prevention of avian and swine-origin flu. Some new developments and concepts in diagnosis, (molecular) epidemiology, and therapy of AIDS, viral hepatitis C, and herpesvirus-associated diseases are outlined. Regulation of immune system has been discussed in a special issue 2010 including some aspects of CNS affections (measles). Mycobacterial infection and its prevention by modern recombinant vaccines have reached new interest, as well as new concepts of vaccination and prophylaxis against several other bacteria. Adaptation to host niches enables immune escape (example brucella) and determines virulence (example N. meningitidis). Chlamydia pneumoniae, previously considered to trigger atherosclerosis, is hypothetically associated to Alzheimer disease, while CMV, another putative trigger of atherosclerosis, gains evidence of oncomodulation in CNS tumor diseases. In terms of globalization, exotic virus infections are increasingly imported from southern countries.

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.

Hepatitis delta: on soft paws across Germany.

INTRODUCTION: Globally, more than 350 million people are considered to be chronic carriers of the hepatitis B virus (HBV) infection; thereof, 15-20 million of these individuals are thought to be coinfected with hepatitis delta virus (HDV). The clinical course depends on the mode of transmission; whereas coinfection commonly resolves, superinfection aggravates the disease and progresses to chronicity in over 90 % of the cases, which, again, results in cirrhosis. OBJECTIVE: Although many tests are performed in HBV carriers, data on the prevalence of anti-HDV-IgG in Germany are only rarely available and outdated. Therefore, we retrospectively evaluated the seroprevalence of anti-HDV-IgG from the results of our routine service. MATERIALS AND METHODS: Between January 2000 and October 2011, serum samples from 2,844 patients (carrying hepatitis B surface antigen) admitted to University Hospital Frankfurt am Main, Frankfurt, Germany, were tested for anti-HDV-IgG by enzyme-linked immunosorbent assay (ELISA). RESULTS: The overall seroprevalence of anti-HDV-IgG in the collective of Frankfurt (n = 2,844) is 7.4 % [95 % confidence interval (CI): 6.4-8.4]. The amount of seropositive men (8.3 %, 95 % CI: 6.9-10) significantly exceeds the female proportion (5.7 %, 95 % CI: 4.3-7.5). The rate of seropositivity to anti-HDV-IgG in this collective of Frankfurt reached a maximum in the year 2003 (10.1 %, 95 % CI: 8.9-11.1). The lowest rate was observable in 2004, where 5.4 % were positive to anti-HDV-IgG. CONCLUSION: Of the HBV carriers in Germany, 5-8 % reveal serologic evidence of coinfection with HDV. The vaccination against HBV is the key to prevent HDV infection; therefore, vaccination must strongly be propagated further on.

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.

[Diagnostic of neurotropic enteroviruses in children with CSF and/or stool: virus isolation by cell culture or PCR?]. / Enterovirusdiagnostik bei aseptischer Meningitis im Kindesalter mit Liquor und/oder Stuhl: Zellkulturgestützte Virusisolierung oder PCR?

BACKGROUND: Aseptic meningitis in children is most frequently caused by enteroviruses. In clinical setting there arises the question, whether stool samples or cerebrospinal fluid (CSF) are better suited for laboratory diagnosis. METHODS: Between 06/2006 and 03/2010 a total number of 613 specimens (376 CSF [61.4%] and 237 stool [38.6%]) of 613 children (270 female [44.1%] and 343 [55.9%] male) aged 22 days to 15 years were collected and investigated by enterovirus-PCR and by virus isolation in cell culture, respectively. RESULTS: Enterovirus was detected in 35.4% (217/613) of the samples by cell culture and/or PCR. In total, specimens of CSF were significantly (p<0.001) more often positive (59.4%, n=129) for enterovirus than stool (40.6%; n=88). Concerning stool, PCR gained no significant advantage when compared to cell culture (35.4% vs. 27.8%; p=0.08), However, virus isolation in cell culture using CSF samples succeeded significantly PCR (30.1% vs. 13.8%; p<0.001). DISCUSSION: Because of its not-invasive sampling, stool is the preferred specimen in suspicion of aseptic meningitis in pediatric clinic. If only stool is available, PCR as well as cell culture are valuable; on contrary, if CSF is available cell culture is significantly superior to PCR in attaining a positive result.

Determination of serum antibodies against swine-origin influenza A virus H1N1/09 by immunofluorescence, haemagglutination inhibition, and by neutralization tests: how is the prevalence rate of protecting antibodies in humans?

In April 2009, a new variant of influenza A virus, subtype H1N1v emerged in Mexico and spread all over the world producing the H1N1 pandemic in mankind after 1918-1920 and 1978/1979. Obviously there was no herd immunity against this new virus variant. Mainly young people, but less elderly were affected and presented severe and even lethal courses of disease. Since virus-specific antibodies are commonly regarded as markers of partial or complete immunoprotection, we performed antibody determinations in serum samples obtained from people before and after the pandemic has arrived in our region (Frankfurt/M., Germany). The assays were done by indirect immunofluorescence, by neutralization test, and by a haemagglutination inhibition test (HI), which was established in a practical modification for general and easy use. Among 145 individuals, of whom serum specimens had been drawn before the onset of pandemic, 19 revealed humoral immunity, i.e. titres of H1N1v neutralizing antibodies (at least 1:64). Eleven were older than 60 years, one belonged to the age group 40-59 years, three to the age group 20-39 years, and two to the age group 15-19 years. After the onset of pandemic in Frankfurt, serum specimens drawn from n = 225 randomly selected patients of our local university hospital were investigated for antibodies against H1N1v by HI, which is generally recommended for routine check of immunity. Twenty-eight individuals revealed the protecting antibody titre of at least 1:40. The age distribution had moved to mean age groups. The results fit to the incidence of influenza A/H1N1(09) disease, as confirmed by RT-PCR in patients admitted to our hospital, peaking in the younger age groups up to 30 years (second affected group: 30-40 years). While commonly used solid-phase antibody tests (like immunofluorescence) are not suitable to diagnose passed H1N1(09) infection and acquired immunity, this can be easily done by HI. Expecting the next waves of influenza A/H1N1v infections, HI testing may avoid vaccinations under special risk of severe or hidden adverse reactions.

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.

Mutations in the C-terminal region of the HIV-1 reverse transcriptase and their correlation with drug resistance associated mutations and antiviral treatment.

OBJECTIVE: replication of HIV-1 after cell entry is essentially dependent on the reverse transcriptase (RT). Antiretroviral drugs impairing the function of the RT currently aim at the polymerase subunit. One reason for failure of antiretroviral treatment is the evolvement of resistance-associated mutations in the viral genome. For RT inhibitors, almost all identified mutations are located within the polymerase; therefore, general genotyping confines to investigate this subunit. Recently several studies have shown that substitutions within the RNase H and the connection domain increase antiviral drug-resistance in vitro, and some of them are present in patient isolates. AIM: the aim of the present study was to investigate the prevalence of these substitutions and their association with mutations in the polymerase domain arising during antiretroviral treatment. MATERIAL AND METHODS: we performed genotypic analyzes on seventy-four virus isolates derived from treated and untreated patients, followed at the HIV Centre of the Johann Wolfgang Goethe University Hospital (Frankfurt/Main, Germany). We subsequently ana?lysed the different substitutions in the c-terminal region to evaluate whether there were associations with each other, n-terminal substitutions or with antiretroviral treatment. RESULTS: We identified several primer grip substitutions, but almost all of them were located in the connection domain. This is consistent with other in-vivo studies, in which especially the primer grip residues located in the RNase H were unvaried. Furthermore, we identified other substitutions in the connection domain and in the RNase H. Especially E399D seemed to be associated with an antiretroviral treatment and N-terminal resistance-delivering mutations. CONCLUSION: some of the identified substitutions were associated with antiviral treatment and drug resistance-associated mutations. Due to the low prevalence of C-terminal mutations and as only a few of them could be associated with antiviral treatment and N-terminal resistance-delivering mutations, we would not recommend routinely testing of the C-terminal RT region.

An influenza A H1N1 virus revival - pandemic H1N1/09 virus.

In April 2009, a novel H1N1 influenza A virus, the so-called pandemic H1N1/09 virus (former designations include swine influenza, novel influenza, swine-origin influenza A [H1N1] virus [S-OIV], Mexican flu, North American Flu) was identified in Mexico. The virus has since spread throughout the world and caused an influenza pandemic as defined by the criteria of the World Health Organization. This represents the first influenza A virus pandemic since the emergence of H3N2 (''Hong Kong'' Flu) in 1968. Vaccine production has started, and vaccines are expected to become available during the course of 2009. Although the pandemic H1N1/09 virus originates from the triple-reassortant swine influenza (H1) virus circulating in North American pigs, it is not epidemic in pigs. Although the H1N1/09 virus pandemic is currently mild, concerns remain that it may become more aggressive during spreading. The distribution of proper information to the public on the status of the H1N1/09 virus pandemic will be important to achieve a broad awareness of the potential risks and the optimum code of behavior during the pandemic. Here, the features of pandemic H1N1/09 virus are discussed within the framework of knowledge gained from previous influenza A virus pandemics.

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.

[Genital herpes and HSV transmission in HIV patients]. / Genitaler Herpes und HSV-Transmission bei HIV-Patienten.

There is a bidirectional relationship between HSV-2 and HIV-1, both at the cellular level, as well as regarding transmission and even progression of HIV-1 infection. There is clear evidence that anti-herpetic therapy reduces the plasma and mucosal HIV-1 viral load, as well as transmission. Serologic testing for HSV-2 in patients with an increased HIV-1 risk, coupled with a better understanding of the interaction between the viruses and appropriate anti-herpetic suppression therapy could both reduce the HIV-1 transmission rate and help the individual with an HIV infection.

Valproic acid induces extracellular signal-regulated kinase 1/2 activation and inhibits apoptosis in endothelial cells.

The histone deacetylase (HDAC) inhibitor valproic acid (VPA) was recently shown to inhibit angiogenesis, but displays no toxicity in endothelial cells. Here, we demonstrate that VPA increases extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation in human umbilical vein endothelial cells (HUVEC). The investigation of structurally modified VPA derivatives revealed that the induction of ERK 1/2 phosphorylation is not correlated to HDAC inhibition. PD98059, a pharmacological inhibitor of the mitogen-activated protein kinase kinase 1/2, prevented the VPA-induced ERK 1/2 phosphorylation. In endothelial cells, ERK 1/2 phosphorylation is known to promote cell survival and angiogenesis. Our results showed that VPA-induced ERK 1/2 phosphorylation in turn causes phosphorylation of the antiapoptotic protein Bcl-2 and inhibits serum starvation-induced HUVEC apoptosis and cytochrome c release from the mitochondria. Moreover, the combination of VPA with PD98059 synergistically inhibited angiogenesis in vitro and in vivo.