Perspectives on vaccination in adults.

In the Second Conference on Controversies in Vaccination in Adults, leading vaccine experts among manufacturers, physicians, microbiologists, virologists, immunologists and public health specialists came together to discuss recent approaches, developments and strategies in vaccination against worldwide pressing epidemic and endemic infectious diseases (pneumococcal, staphylococcal, influenza, papillomavirus-associated tumors, varicella-zoster, AIDS and tuberculosis), and noninfectious epidemics (atherosclerosis and smoking) outlining arguments surrounding the progress of vaccines.

Prevalence of herpes simplex virus type 2 in different risk groups: thirty years after the onset of HIV.

BACKGROUND: Herpes simplex virus type 2 (HSV2) is a sexually transmitted disease causing a lifelong persisting infection. OBJECTIVE: To determine the seroprevalence of anti-HSV2-IgG in a German collective. We evaluate the German serological status, point out trends in the chronological spread of HSV2 infection, and position our findings in a global context. METHODS: Serum samples from 29,694 patients at the University Hospital Frankfurt am Main, Germany, were screened for anti-HSV2-IgG using ELISA. We evaluated five defined groups containing patients from the departments of pediatrics (PED), gynecology (GYN), dermatology (DER), psychiatrics (PSY) and patients suffering from HIV/AIDS (HIV). RESULTS: We retrospectively evaluated an overall seropositivity to anti-HSV2-IgG of 13.6% (95% CI 13.1-14.1), with a significantly higher level in females (15.9%, 95% CI 15.4-16.5) than in males (11.4%, 95% CI 10.9-11.9). The highest seroprevalence was detected in HIV (34.7%, 95% CI 30.3-39.3). The lowest rate was observed in PED (9.9%, 95% CI 9.4-10.6) with an estimated number of 18 infections at delivery between 1/1/2000 and 1/1/2011. CONCLUSIONS: HSV2 infections are widespread in Germany with a tremendous health risk for newborns. Therefore, the public's perception of HSV2 should be strengthened and protected sexual intercourse should be propagated.

Chemotherapy-associated angiogenesis in neuroblastoma tumors.

The influences of cytotoxic drugs on endothelial cells remain incompletely understood. Herein, we examined the effects of chemotherapeutic agents in experimental angiogenesis models and analyzed vessel densities in clinical neuroblastoma tumor samples. Cisplatin (20 to 500 ng/mL), doxorubicin (4 to 100 ng/mL), and vincristine (0.5 to 4 ng/mL), drugs commonly involved in neuroblastoma therapy protocols, induced pro-angiogenic effects in different angiogenesis models. They enhanced endothelial cell tube formation, endothelial cell sprouting from spheroids, formation of tip cells in the sprouting assay, expression of αvß3 integrin, and vitronectin binding. All three drugs increased global cellular kinase phosphorylation levels, including the angiogenesis-relevant molecules protein kinase Cß and Akt. Pharmacological inhibition of protein kinase Cß or Akt upstream of phosphatidylinositol 3-kinase reduced chemotherapy-induced endothelial cell tube formation. Moreover, the investigated chemotherapeutics dose dependently induced vessel formation in the chick chorioallantoic membrane assay. Tumor samples from seven high-risk patients with neuroblastoma were analyzed for vessel density by IHC. Results revealed that neuroblastoma samples taken after chemotherapy consistently showed an enhanced microvessel density compared with the corresponding samples taken before chemotherapy. In conclusion, our data show that chemotherapy can activate endothelial cells by inducing multiple pro-angiogenic signaling pathways and exert pro-angiogenic effects in vitro and in vivo. Moreover, we report a previously unrecognized clinical phenomenon that might, in part, be explained by our experimental observations: chemotherapy-associated enhanced vessel formation in tumors from patients with neuroblastoma.

Deficiency of immunity to poliovirus type 3: a lurking danger?

BACKGROUND: Europe was certified to be polio-free in 2002 by the WHO. However, wild polioviruses remain endemic in India, Pakistan, Afghanistan, and Nigeria, occasionally causing polio outbreaks, as in Tajikistan in 2010. Therefore, effective surveillance measures and vaccination campaigns remain important. To determine the poliovirus immune status of a German study population, we retrospectively evaluated the seroprevalence of neutralizing antibodies (NA) to the poliovirus types 1, 2 and 3 (PV1, 2, 3) in serum samples collected from 1,632 patients admitted the University Hospital of Frankfurt am Main, Germany, in 2001, 2005 and 2010. METHODS: Testing was done by using a standardized microneutralization assay. RESULTS: Level of immunity to PV1 ranged between 84.2% (95%CI: 80.3-87.5), 90.4% (88.3-92.3) and 87.5% (85.4-88.8) in 2001, 2005 and 2010. For PV2, we found 90.8% (87.5-90.6), 91.3% (89.3-93.1) and 89.8% (88.7-90.9), in the same period. Seroprevalence to PV3 was 76.6% (72.2-80.6), 69.8% (66.6-72.8) and 72.9% (67.8-77.5) in 2001 and 2005 and 2010, respectively. In 2005 and 2010 significant lower levels of immunity to PV3 in comparison to PV1 and 2 were observed. Since 2001, immunity to PV3 is gradually, but not significantly decreasing. CONCLUSION: Immunity to PV3 is insufficient in our cohort. Due to increasing globalization and worldwide tourism, the danger of polio-outbreaks is not averted - even not in developed countries, such as Germany. Therefore, vaccination remains necessary.

Prevalence of TMC278 (rilpivirine) associated mutations in the Frankfurt Resistance Database.

BACKGROUND: Analysis of the 3D structure of the HIV-1 reverse transcriptase led to the development of TMC278 (rilpivirine), a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), which proved to be effective against wild-type HIV-1 strains and NNRTI-resistant mutants emerging after failure of NNRTI-containing therapy regimens. Recently, rilpivirine associated mutations (e.g. at positions 138, 181 or 101) have been described in vitro and in vivo; however, some of these mutations have also been observed in the past. OBJECTIVE: Objective of our investigation was to determine the prevalence of mutations E138K, Y181I/V, and K101E/P before the approval of rilpivirine. STUDY DESIGN: The Frankfurt Resistance Database consists of 7295 samples which have been sent for resistance testing since 1995. RESULTS: The E138K, Y181I/V, and the K101E mutations were found in 0.4%, 0.9%, and 2.4% of the patients, respectively. CONCLUSIONS: Based on these findings we do not expect a broad cross-resistance to rilpivirine due to previous treatment failures of NNRTI-containing regimens.

Comparison of drug resistance scores for tipranavir in protease inhibitor-naive patients infected with HIV-1 B and non-B subtypes.

Genotypes of samples from protease inhibitor-naïve patients in Frankfurt's HIV Cohort were analyzed with five tipranavir resistance prediction algorithms. Mean scores were higher in non-B than in B subtypes. The proportion of non-B subtypes increased with increasing scores, except in weighted algorithms. Virtual and in vitro phenotype analyses of samples with increased scores showed no reduced tipranavir susceptibility. Current algorithms appear suboptimal for interpretation of resistance to tipranavir in non-B subtypes; increased scores might reflect algorithm bias rather than "natural resistance."

Immune response after two doses of the novel split virion, adjuvanted pandemic H1N1 influenza A vaccine in HIV-1-infected patients.

BACKGROUND: To determine the rate of seroconversion after 2 doses of a novel split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in human immunodeficiency virus type 1 (HIV-1)-infected patients (ClinicalTrials.gov NCT01017172). METHODS: Diagnostic study of adult HIV-1-infected patients scheduled for H1N1 influenza A vaccination. Blood samples where taken before and 21 days after the first dose and 21 days after the second dose of the vaccine. Antibody (AB) titers were determined by hemagglutination inhibition assay. Seroconversion was defined by either an AB titer ≤ 1:10 before and ≥ 1:40 after or ≥ 1:10 before and a ≥ 4-fold increase in AB titer 21 days after vaccination. RESULTS: One hundred thirty-five patients received 2 doses of the H1N1 vaccine and were analyzed. The rate of seroconversion was 68.2% (95% confidence interval, 59.6-75.9) after the first dose and 91.9% (95% confidence interval, 85.9-95.9) after the second dose. Patients who did not seroconvert had a lower mean nadir CD4 cell count (± standard deviation; 81 ± 99 vs 190 ± 148 cells/µL; P = .006), had a longer duration of HIV infection (± standard deviation; 13.1 ± 5.9 vs 8.8 ± 6.8 years; P = .04), and were more likely to have an AB titer ≥ 1:40 before vaccination (4% vs 55%; P < .001) when compared with patients with seroconversion. No other differences were found between the 2 groups, including AIDS status, highly active antiretroviral therapy status, HIV RNA - polymerase chain reaction load <50 copies/mL, CD4 cell count, sex, body mass index, and chronic hepatitis. CONCLUSION: Among HIV-infected patients, the rate of seroconversion after the first dose of an adjuvanted H1N1 influenza A vaccine was 68% and increased to 92% after a second doses.

Immunity status of adults and children against poliomyelitis virus type 1 strains CHAT and Sabin (LSc-2ab) in Germany.

BACKGROUND: In October 2007, the working group CEN/TC 216 of the European Committee for standardisation suggested that the Sabin oral poliovirus vaccine type 1 strain (LSc-2ab) presently used for virucidal tests should be replaced by another attenuated vaccine poliovirus type 1 strain, CHAT. Both strains were historically used as oral vaccines, but the Sabin type 1 strain was acknowledged to be more attenuated. In Germany, vaccination against poliomyelitis was introduced in 1962 using the oral polio vaccine (OPV) containing Sabin strain LSc-2ab. The vaccination schedule was changed from OPV to an inactivated polio vaccine (IPV) containing wild polio virus type 1 strain Mahoney in 1998. In the present study, we assessed potential differences in neutralising antibody titres to Sabin and CHAT in persons with a history of either OPV, IPV, or OPV with IPV booster. METHODS: Neutralisation poliovirus antibodies against CHAT and Sabin 1 were measured in sera of 41 adults vaccinated with OPV. Additionally, sera from 28 children less than 10 years of age and immunised with IPV only were analysed. The neutralisation assay against poliovirus was performed according to WHO guidelines. RESULTS: The neutralisation activity against CHAT in adults with OPV vaccination history was significantly lower than against Sabin poliovirus type 1 strains (Wilcoxon signed-rank test P < 0.025). In eight sera, the antibody titres measured against CHAT were less than 8, although the titre against Sabin 1 varied between 8 and 64. Following IPV booster, anti-CHAT antibodies increased rapidly in sera of CHAT-negative adults with OPV history. Sera from children with IPV history neutralised CHAT and Sabin 1 strains equally. CONCLUSION: The lack of neutralising antibodies against the CHAT strain in persons vaccinated with OPV might be associated with an increased risk of reinfection with the CHAT polio virus type 1, and this implies a putative risk of transmission of the virus to polio-free communities. We strongly suggest that laboratory workers who were immunised with OPV receive a booster vaccination with IPV before handling CHAT in the laboratory.

Low rate of seroconversion after vaccination with a split virion, adjuvanted pandemic H1N1 influenza vaccine in HIV-1-infected patients.

OBJECTIVE: To determine rates of seroconversion after single vaccination with a novel split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in HIV-1-infected patients (ClinicalTrials.gov Identifier: NCT01017172). DESIGN: Single center diagnostic study. SETTING: Institutional HIV outpatient department of an urban university clinic. PARTICIPANTS: Adult HIV-1-infected individuals. INTERVENTION: Serum samples were taken before and 21 days after vaccination. MAIN OUTCOME MEASURES: Antibody titers determined by hemagglutination inhibition assay. Seroconversion to vaccination was defined by either an antibody titer of 1: 10 or less before and of at least 1: 40 after or at least 1: 10 before and at least four-fold increase in antibody titer 21 days after single vaccination. RESULTS: One hundred and sixty patients (125 men/35 women) were analyzed. Before vaccination, 23 patients (14.4%) had a hemagglutination inhibition assay titer of at least 1: 40. A median of 22 +/- 3 days after vaccination, 110 (69%) patients seroconverted. Seroconverters were younger (45.1 +/- 10.0 vs. 48.8 +/- 11.3 years; P = 0.04), had a higher CD4 cell count (532 +/- 227 vs. 475 +/- 281 cells/microl; P = 0.03) and were more likely to have received a previous H5N1 vaccination in 2009 (25 vs. 8%; P = 0.02) when compared to nonresponders. No other significant differences were found comparing the two groups (prevaccination hemagglutination inhibition assay titer of > or =1: 40, AIDS, HAART, HIV RNA PCR <50 copies/ml or CD4 nadir, CD4 and CD8 percentage, sex, BMI, chronic hepatitis B or C). CONCLUSION: Seroconversion after one dose of a split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine of HIV-infected patients was 69%. Studies to investigate whether a second dose of the vaccine will increase seroconversion rate are needed.

Regional spread of HIV-1 M subtype B in middle-aged patients by random env-C2V4 region sequencing.

A transmission cluster of HIV-1 M:B was identified in 11 patients with a median age of 52 (range 26-65) in North-East Germany by C2V4 region sequencing of the env gene of HIV-1, who-except of one-were not aware of any risky behaviour. The 10 male and 1 female patients deteriorated immunologically, according to their information made available, within 4 years after a putative HIV acquisition. Nucleic acid sequence analysis showed a R5 virus in all patients and in 7 of 11 a crown motif of the V3 loop, GPGSALFTT, which is found rarely. Analysis of formation of this cluster showed that there is still a huge discrepancy between awareness and behaviour regarding HIV transmission in middle-aged patients, and that a local outbreak can be detected by nucleic acid analysis of the hypervariable env region.

Chemoresistance acquisition induces a global shift of expression of aniogenesis-associated genes and increased pro-angogenic activity in neuroblastoma cells.

BACKGROUND: Chemoresistance acquisition may influence cancer cell biology. Here, bioinformatics analysis of gene expression data was used to identify chemoresistance-associated changes in neuroblastoma biology. RESULTS: Bioinformatics analysis of gene expression data revealed that expression of angiogenesis-associated genes significantly differs between chemosensitive and chemoresistant neuroblastoma cells. A subsequent systematic analysis of a panel of 14 chemosensitive and chemoresistant neuroblastoma cell lines in vitro and in animal experiments indicated a consistent shift to a more pro-angiogenic phenotype in chemoresistant neuroblastoma cells. The molecular mechanisms underlying increased pro-angiogenic activity of neuroblastoma cells are individual and differ between the investigated chemoresistant cell lines. Treatment of animals carrying doxorubicin-resistant neuroblastoma xenografts with doxorubicin, a cytotoxic drug known to exert anti-angiogenic activity, resulted in decreased tumour vessel formation and growth indicating chemoresistance-associated enhanced pro-angiogenic activity to be relevant for tumour progression and to represent a potential therapeutic target. CONCLUSION: A bioinformatics approach allowed to identify a relevant chemoresistance-associated shift in neuroblastoma cell biology. The chemoresistance-associated enhanced pro-angiogenic activity observed in neuroblastoma cells is relevant for tumour progression and represents a potential therapeutic target.

Accelerated telomere shortening in leukocyte subpopulations of patients with coronary heart disease: role of cytomegalovirus seropositivity.

BACKGROUND: Shortening of mean telomere length (TL) in white blood cells is correlated with the development of coronary heart disease (CHD) and with increased mortality due to infectious disease. The goal of the present study was to investigate whether telomere shortening in CHD is restricted to specific peripheral blood lymphocyte and/or myeloid cell subpopulations. Results were correlated to TL in CD34+ hematopoietic peripheral blood stem cells and progenitor cells obtained from the same individual patients. METHODS AND RESULTS: TL was measured by multicolor flow cytometry-fluorescent in situ hybridization in 12 leukocyte subpopulations after immunomagnetic bead sorting. We investigated TL in 14 young (mean age 25 years) and 13 older (mean age 65 years) healthy male volunteers and in 25 age-matched patients with CHD (mean age 65 years). We show that TL in granulocytes and monocytes mirrors TL of CD34+ peripheral blood stem cells and progenitor cells extremely well (r=0.95, P<0.0001) in patients and in healthy adults. TL was approximately 0.5 kilobases (kb) shorter in leukocytes from patients with CHD than in their age-matched control subjects. This difference was identical for CD34+ peripheral blood stem cells and progenitor cells, monocytes, granulocytes, B lymphocytes, and CD4+ T cells, including their memory and naïve subpopulations. Surprisingly, only in cytotoxic CD8+ T lymphocytes, we found a substantially increased TL deficit of 1.0 kb in CHD patients as opposed to control subjects. Further analysis revealed that TL shortening was particularly pronounced in CD8+CD28(-) T cells obtained from cytomegalovirus-seropositive CHD patients, whereas such a difference was not observed in healthy cytomegalovirus-positive as opposed to cytomegalovirus-negative control subjects. Finally, TL shortening of CD8+CD45(RA+) T cells was correlated with the decrease in left ventricular function in CHD patients (r=0.629, P=0.001). CONCLUSIONS: Telomere shortening in patients with CHD could potentially be attributed to either inherited TL shortening or acquired accelerated telomere shortening restricted to the hematopoietic system, which affects the baseline TL of all peripheral blood cell populations, including peripheral blood stem cells and progenitor cells. In addition, cytomegalovirus-seropositive patients but not healthy control subjects exhibited further shortening of their cytotoxic T lymphocytes. Surprisingly, TL shortening of CD8+ T lymphocytes in CHD patients demonstrated a very strong correlation with cardiac dysfunction, which suggests a mechanistic link between CHD and immunosenescence.

Screening for infectious diseases at international airports: the Frankfurt model.

Historically, ships brought infectious diseases to the continents of the world, but in this modern era, infectious diseases and pandemics are primarily spread through aviation as a mode of travel. This is a significant issue in the realm of infection control because of the increased potential for the rapid worldwide transmission and spread of disease. Although the transmission of infectious diseases to airline passengers inside an aircraft is a rare occurrence, it is essential to implement entry and exit screening procedures at airports within the context of the International Health Regulations (IHR) in order to slow down the spread of infection, especially during the early phases of a pandemic event. Currently, there are no standardized procedures for health screening at airports, thus allowing individual regional authorities to determine what they deem to be appropriate screening measures for implementation. In this paper, we will discuss a new pragmatic approach for entry and exit screening procedures at international airports, propose a new classification system for contacts within the aircraft, and discuss changing the fixed enforcement of standardized community mitigation measures to the implementation of measures that correspond to specific characteristics of individual pathogenic agents. The proposed catalog of screening measures is aimed at attaining the goals of the IHR, which states that the measures should be reasonable while avoiding inconvenience or harm to passengers and should not be any more disruptive to the smooth handling of passenger traffic than is necessary.

The story of human cytomegalovirus and cancer: increasing evidence and open questions.

Although human cytomegalovirus (HCMV) is generally not regarded to be an oncogenic virus, HCMV infection has been implicated in malignant diseases from different cancer entities. On the basis of our experimental findings, we developed the concept of "oncomodulation" to better explain the role of HCMV in cancer. Oncomodulation means that HCMV infects tumor cells and increases their malignancy. By this concept, HCMV was proposed to be a therapeutic target in a fraction of cancer patients. However, the clinical relevance of HCMV-induced oncomodulation remains to be clarified. One central question that has to be definitively answered is if HCMV establishes persistent virus replication in tumor cells or not. In our eyes, recent clinical findings from different groups in glioblastoma patients and especially the detection of a correlation between the numbers of HCMV-infected glioblastoma cells and tumor stage (malignancy) strongly increase the evidence that HCMV may exert oncomodulatory effects. Here, we summarize the currently available knowledge about the molecular mechanisms that may contribute to oncomodulation by HCMV as well as the clinical findings that suggest that a fraction of tumors from different entities is indeed infected with HCMV.

Incidence and clinical outcome of cytomegalovirus transmission via breast milk in preterm infants

AIM: To evaluate incidence, timing and clinical relevance of acquired human cytomegalovirus (HCMV) infection in preterm infants. METHODS: The prospective longitudinal study included preterm infants

Short communication: Different mutation patterns in subtype CRF06_cpx after mother-to-child transmission.

Abstract Development of drug resistance mutation patterns (DRMP) in HIV after treatment failure depends on the drugs used in the failing regimen. However, selected patterns may not be unique; there is evidence that selection of DRMP for nelfinavir is dependent on subtype and/or background polymorphisms. Here we describe the selection of DRMP in a mother and son infected with subtype CRF06_cpx by mother-to-child transmission. Four years after delivery the mother received stavudine/lamivudine/nelfinavir as first-line therapy. Genotypic resistance tests (GRT) during follow-up showed selection of M184V/L283I in reverse transcriptase (RT) and H63Q/A71V/L90M in protease (PR). The child started treatment 8 months after birth with stavudine/didanosine/nelfinavir followed by an intensification period with efavirenz. Due to toxicity, efavirenz was removed from the regimen again. GRT during follow-up showed selection of L74V/K103N/M184V/M230L in RT and M46I/H63Q/N88S in PR. The viral load (VL) of the mother was initially undetectable followed by intermediate replication (1000-21,000 copies/ml), whereas the child had both periods of undetectable VL and low-level replication. Although both patients were infected with the same virus and treated with the same protease inhibitor, different DRMPs were selected. Whether the nucleoside backbone, course of antiretroviral therapy, or different host environment is responsible for this variability must be determined in larger studies.

Cisplatin-resistant neuroblastoma cells express enhanced levels of epidermal growth factor receptor (EGFR) and are sensitive to treatment with EGFR-specific toxins.

PURPOSE: Neuroblastomas frequently show expression of the epidermal growth factor receptor (EGFR) and may therefore be susceptible to EGFR-targeted therapies. Here, EGFR expression and functionality was investigated in parental chemosensitive neuroblastoma cell lines (UKF-NB-3, IMR-32, NLF, SH-SY5Y) and their cisplatin-resistant sublines (UKF-NB-3(r)CDDP(1000), IMR-32(r)CDDP(1000), NLF(r)CDDP(1000), and SH-SY5Y(r)CDDP(500)). Moreover, the EGFR antibody cetuximab, the EGFR tyrosine kinase inhibitor Tyrphostin B46, and recombinant EGFR-targeted toxins were investigated for their influence on the viability and growth of neuroblastoma cells. EXPERIMENTAL DESIGN: EGFR expression and function was measured by flow cytometry or Western blot. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was examined by immunostaining for active caspase-3 or cleaved poly(ADP-ribose) polymerase. Cellular binding of FITC-labeled immunotoxins was studied by flow cytometry, and cellular uptake was studied by confocal laser scanning microscopy. RESULTS: The EGFR-targeted antibody and growth factor toxins scFv(14E1)- Pseudomonas exotoxin A (ETA) and TGF-alpha-ETA exerted anti-cancer effects in neuroblastoma cell lines that were insensitive to cetuximab or EGFR tyrosine kinase inhibitors. Furthermore, adaptation of chemosensitive neuroblastoma cells to cisplatin increased EGFR expression and sensitivity to both recombinant toxins. Treatment of chemosensitive neuroblastoma cells with cisplatin reversibly increased EGFR expression, whereas cisplatin-resistant cells showed enhanced EGFR expression independent of the presence of cisplatin. Combination treatment with scFv(14E1)-ETA or TGF-alpha-ETA and cisplatin exerted significantly improved anticancer effects compared with either single treatment in parental neuroblastoma cells, cisplatin-resistant sublines, and primary cultures. CONCLUSIONS: EGFR-targeted cytotoxic reagents such as scFv(14E1)-ETA and TGF-alpha-ETA represent promising candidates for further development as antineuroblastoma agents, especially in combination with cisplatin.

Is transmission of HIV-1 in non-viraemic serodiscordant couples possible?

Several studies have shown that HIV-1 transmission in serodiscordant couples is significantly reduced when the plasma viral load (pVL) in the infected partner is low or undetectable. However, residual infectivity in the seminal compartment despite undetectable pVL has also been shown. Here we report HIV-1 transmission in a serodiscordant couple despite successful antiretroviral therapy of the HIV-infected partner. The newly infected partner had a negative HIV-1 screening ELISA when his HIV-1-positive partner was already on antiretroviral treatment with undetectable pVL, which remained undetectable beyond the time of seroconversion in the initially negative partner. Frozen blood samples were analyzed phylogenetically from the HIV-1-positive patient and the newly infected partner before treatment and shortly after seroconversion, respectively; they showed a true relationship. On the basis of these data, the present report suggests that transmission of HIV-1 can occur despite undetectable pVL. This should be added to the discussion of prevention strategies, which should not advise the abandonment of safer-sex practices without referring to the relatively low but not impossible risk of HIV-1 transmission in this context.

Determination of risk of infection with blood-borne pathogens following a needlestick injury in hospital workers.

OBJECTIVES: Our paper measures the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in patients at the University Hospital of Frankfurt/Main, and correlates the prevalence with risk factors for exposure to and infection of healthcare workers (HCWs). Individual risk assessments were calculated for exposed HCWs. METHODS: Survey of patients admitted to a German University Hospital. Markers for HBV, HCV and HIV were studied and evaluated statistically. Data on needlestick injuries (NSIs) among HCWs were correlated with the prevalence of infectious patients. RESULTS: The HBV, HCV and HIV prevalence among patients at the University Hospital were 5.3% (n = 709/13 358), 5.8% (n = 1167/20 163) and 4.1% (n = 552/13 381), respectively. Our results indicate that the prevalence of blood-borne infections in patients was about nine times higher for HBV, approximately 15 times higher for HCV and approximately 82 times higher for HIV than in the overall German population. The highest risk of acquiring a blood-borne infection via NSI was found in the department of internal medicine due to increased prevalence of blood-borne pathogens in patients under treatment. CONCLUSIONS: While accidental NSIs were most frequent in surgery, the nominal risk of blood-borne virus infection was greatest in the field of internal medicine. The study underlines the importance of HBV vaccinations and access to HIV-post-exposure prophylaxis for HCWs as well as the use of anti-needlestick devices.

The threat of avian influenza A (H5N1). Part IV: Development of vaccines.

Among emerging and re-emerging infectious diseases, influenza constitutes one of the major threats to mankind. In this review series epidemiologic, virologic and pathologic concerns raised by infections of humans with avian influenza virus A/H5N1 are discussed. This fourth part focuses on vaccine development. Several phase I clinical studies with vaccines against H5 viruses have demonstrated limited efficacy compared to seasonal influenza vaccines. To induce protective immunity two immunisations with increased amounts of H5N1 vaccine were required. Novel vaccination strategies that are egg- and adjuvant-independent, broadly cross-reactive and long-lasting are highly desirable.