Dissection of antibody specificities induced by yellow fever vaccination.

The live attenuated yellow fever (YF) vaccine has an excellent record of efficacy and one dose provides long-lasting immunity, which in many cases may last a lifetime. Vaccination stimulates strong innate and adaptive immune responses, and neutralizing antibodies are considered to be the major effectors that correlate with protection from disease. Similar to other flaviviruses, such antibodies are primarily induced by the viral envelope protein E, which consists of three distinct domains (DI, II, and III) and is presented at the surface of mature flavivirions in an icosahedral arrangement. In general, the dominance and individual variation of antibodies to different domains of viral surface proteins and their impact on neutralizing activity are aspects of humoral immunity that are not well understood. To gain insight into these phenomena, we established a platform of immunoassays using recombinant proteins and protein domains that allowed us to dissect and quantify fine specificities of the polyclonal antibody response after YF vaccination in a panel of 51 vaccinees as well as determine their contribution to virus neutralization by serum depletion analyses. Our data revealed a high degree of individual variation in antibody specificities present in post-vaccination sera and differences in the contribution of different antibody subsets to virus neutralization. Irrespective of individual variation, a substantial proportion of neutralizing activity appeared to be due to antibodies directed to complex quaternary epitopes displayed on the virion surface only but not on monomeric E. On the other hand, DIII-specific antibodies (presumed to have the highest neutralizing activity) as well as broadly flavivirus cross-reactive antibodies were absent or present at very low titers. These data provide new information on the fine specificity as well as variability of antibody responses after YF vaccination that are consistent with a strong influence of individual-specific factors on immunodominance in humoral immune responses.

Nephropathy in illicit drug abusers: a postmortem analysis.

BACKGROUND: Illicit drug abuse is an independent risk factor for chronic kidney disease, but the pathogenic consequences of long-term exposure to illicit drugs and contaminants under unsterile conditions remains unclear. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: All deceased persons (n 5 129) who underwent forensic autopsy because of suspected connection with illicit drug abuse between January 1, 2009, and April 30, 2011, in Frankfurt/Main, Germany. PREDICTOR: Clinical characteristics and patterns of drug abuse. OUTCOMES: Histopathologic alterations of the kidney. MEASUREMENTS: Hematoxylin and eosin, periodic acid-Schiff, Sirius, and Congo Red stainings and immunoglobulin A immunohistochemistry of all cases; additional histochemical stainings or immunohistochemistry and electron microscopy in selected cases. RESULTS: Individuals were mostly white (99.2%), were male (82.2%), and had intravenous drug use (IVDU) (81.4%). Median age at death was 39 years and duration of drug abuse was 17 years. The majority (79.1%) took various drugs in parallel as assessed by toxicologic analysis. Despite a young age, the deceased had a high burden of comorbid conditions, especially cardiovascular disease, liver cirrhosis, and infections. Evaluation of the kidneys demonstrated a broad spectrum of pathologic alterations predominated by arteriosclerotic and ischemic damage, mild interstitial inflammation, calcification of renal parenchyma, and interstitial fibrosis and tubular atrophy, with hypertensive-ischemic nephropathy as the most common cause of nephropathy. Interstitial inflammation (OR, 16.59; 95% CI, 3.91-70.39) and renal calcification (OR, 2.43; 95% CI, 1.03- 5.75) were associated with severe IVDU, whereas hypertensive and ischemic damage were associated with cocaine abuse (OR, 6.00; 95% CI, 1.27-28.44). Neither specific glomerular damage indicative for heroin and hepatitis C virus-related disease nor signs of analgesic nephropathy were found. LIMITATIONS: White population, lack of a comparable control group, incomplete clinical data, and absence of routine immunohistochemistry and electron microscopy. CONCLUSIONS: Illicit drug abuse is associated with a broad but unspecific spectrum of pathologic alterations of the kidneys. Cocaine abuse has a deleterious role in this setting by promoting hypertensive and ischemic damage.

Low vitamin D serum concentration is associated with high levels of hepatitis B virus replication in chronically infected patients.

UNLABELLED: Vitamin D is an important immune modulator that plays an emerging role in inflammatory and metabolic liver diseases, including infection with hepatitis C virus (HCV). In contrast, the relationship between vitamin D metabolism and chronic hepatitis B (CHB) is less well characterized. Therefore, we quantified 25(OH)D3 serum levels in a cohort of 203 treatment-naïve patients with chronic hepatitis B virus (HBV) infection and tested for their association with clinical parameters of CHB. Of 203 patients, 69 (34%), 95 (47%), and 39 (19%) had severe vitamin D deficiency (25(OH)D3 <10 ng/mL), vitamin D insufficiency (25(OH)D3 ≥10 and <20 ng/mL), or adequate vitamin D serum levels (25(OH)D3 ≥20 ng/mL), respectively. In both uni- and multivariate analyses, HBV DNA viral load (log10 IU/mL) was a strong predictor of low 25(OH)D3 serum levels (P = 0.0007 and P = 0.000048, respectively) and vice versa. Mean 25(OH)D3 serum concentrations in patients with HBV DNA <2,000 versus ≥2,000 IU/mL were 17 versus 11 ng/mL, respectively (P < 0.00001). In addition, hepatitis B early antigen (HBeAg)-positive patients had lower 25(OH)D3 serum levels than HBeAg-negative patients (P = 0.0013). Finally, 25(OH)D3 and HBV DNA serum levels showed inverse seasonal fluctuations. CONCLUSION: Low 25(OH)D3 serum levels are associated with high levels of HBV replication in patients with CHB. This represents a major difference from chronic hepatitis C, where numerous previous studies have shown a lack of correlation between HCV viral load and vitamin D serum levels. Inverse seasonal fluctuations of 25(OH)D3 and HBV DNA serum levels are suggestive of a functional relationship between both variables.

Durability of protective antibody titres is not enhanced by a two-dose schedule of an ASO3-adjuvanted pandemic H1N1 influenza vaccine in adult HIV-1-infected patients.

The immune response after influenza vaccination is impaired in HIV-infected individuals and can be enhanced by a second dose. The durability of the antibody protection and its clinical benefit is not known. We investigated clinical symptoms and antibody titres against H1N1 influenza A following no dose, 1 dose, or 2 doses of an ASO3-adjuvanted H1N1 vaccine in HIV-infected patients. Seroprotection was found in 7.9%, 52.2%, and 57.3% of patients who received no dose, 1 dose, and 2 doses of the vaccine, respectively (p-value for group comparison < 0.001), after a median of 8.2 ± 1.6 months. Clinical symptoms suggestive of an influenza-like illness were slightly more frequently reported in the unvaccinated group. Vaccinated HIV-infected patients were more likely to be seroprotected at follow-up, but there was no difference comparing those who had received 1 or 2 doses of the vaccine.

Immune response after a single dose of the 2010/11 trivalent, seasonal influenza vaccine in HIV-1-infected patients and healthy controls.

BACKGROUND: Immune response rates following influenza vaccination are often lower in HIV-infected individuals. Low vitamin D levels were correlated with weak immune response in cancer patients and are known to be lower in HIV-infected patients. METHODS: Diagnostic study to determine immune response against the H1N1v component after a single, intramuscular dose of the 2010/11 seasonal, trivalent influenza vaccine (TIV) in adult HIV-infected and healthy controls scheduled for influenza vaccination (ClinicalTrials.gov Identifier: NCT01017172). Influenza A/H1N1 antibody titers (AB) were determined before and 21 days after vaccination by hemagglutination inhibition assay. RESULTS: Immune response was not different between HIV-infected patients (n = 36) and healthy controls (n = 42) who were previously naïve to the H1N1v component of the TIV. Comparing HIV-infected patients (n = 55) and healthy controls (n = 63) who had received 1 or 2 doses of an AS03 adjuvanted H1N1 vaccine in the previous winter season (2009/10), seroconversion rate and the geometric mean AB titer after TIV of the HIV-infected patients were more than twice as high compared to healthy controls. This difference was mainly driven by the 2-dose schedule for HIV patients in 2009/10. Vitamin D levels were lower in HIV patients but did not correlate with immune response. CONCLUSION: HIV-infected patients who had received 1 or 2 doses of an adjuvanted H1N1 vaccine in the previous year (2009/10) had a significant higher seroconversion rate following TIV as compared to healthy controls, indicating a stronger memory cell response due to the 2-dose schedule.

Hepatitis E: are psychiatric patients on special risk?

Hepatitis E virus (HEV) is largely confined to travelers returning from endemic areas, but the number of autochthonous cases of acute HEV infections in developed countries is increasing. Reservoirs for HEV are surface water, wild boar meat, and raw or undercooked pork meat. Usually, hepatitis E is a self-limiting disease presenting with acute hepatitis as a major clinical symptom. The seroprevalence of anti-HEV-IgG was investigated in 833 serum samples routinely collected from patients admitted to the university hospital in Frankfurt a. M., Germany (FFM) between 01.06.2008 and 31.12.2010. After determination of overall seroprevalence, we tested serum samples from patients diagnosed with acute elevation of liver enzymes (AELE), psychiatric (PSYCH), infectiological patients and serum samples from the red-cross blood donor service in FFM for anti-HEV-IgG using an ELISA. Between 01.06.2008 and 31.12.2010, 833 serum samples were analyzed for anti-HEV-IgG using an ELISA. We observed an overall seroprevalence of anti-HEV-IgG of 11.2% (95%CI: 9.6-13.2). Significantly higher rate of seropositivity was found in the group of PSYCH (26.0%; 95%CI: 14.63-40.34) and AELE (30.0%; 95%CI: 17.86-44.61). Overall seroprevalence of anti-HEV-IgG in FFM is higher than in Germany on average. The group of AELE and PSYCH shows significantly more often marker of HEV infections than other groups in our collective.

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.

Enhanced immune response after a second dose of an AS03-adjuvanted H1N1 influenza A vaccine in patients after hematopoietic stem cell transplantation.

Seroconversion rates following influenza vaccination in patients with hematologic malignancies after hematopoietic stem cell transplantation (HSCT) are known to be lower compared to healthy adults. The aim of our diagnostic study was to determine the rate of seroconversion after 1 or 2 doses of a novel split virion, inactivated, AS03-adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in HSCT recipients (ClinicalTrials.gov Identifier: NCT01017172). Blood samples were taken before and 21 days after a first dose and 21 days after a second dose of the vaccine. Antibody (AB) titers were determined by hemagglutination inhibition assay. Seroconversion was defined by either an AB titer of ≤ 1:10 before and ≥ 1:40 after or ≥ 1:10 before and ≥ 4-fold increase in AB titer 21 days after vaccination. Seventeen patients (14 allogeneic, 3 autologous HSCT) received 1 dose and 11 of these patients 2 doses of the vaccine. The rate of seroconversion was 41.2% (95% confidence interval [CI] 18.4-67.1) after the first and 81.8% (95% CI 48.2-97.7) after the second dose. Patients who failed to seroconvert after 1 dose of the vaccine were more likely to receive any immunosuppressive agent (P = .003), but time elapsed after or type of HSCT, age, sex, or chronic graft-versus-host disease was not different when compared to patients with seroconversion. In patients with hematologic malignancies after HSCT the rate of seroconversion after a first dose of an adjuvanted H1N1 influenza A vaccine was poor, but increased after a second dose.

Revaccination of children after completion of standard chemotherapy for acute lymphoblastic leukaemia: a pilot study comparing different schedules.

Given that a significant proportion of children with acute lymphoblastic leukaemia (ALL) lose immune protection to tetanus, diphtheria, and poliomyelitis, revaccination is indicated after chemotherapy. Our randomized pilot study comparing different revaccination schedules suggests that children with ALL might be revaccinated with non-live vaccines as early as 3 months after chemotherapy.

Significant increase in travel-associated dengue fever in Germany.

Increasing numbers of dengue fever (DF) cases reflect the increasing travel mobility together with the expanding geographical distribution of the vector Aedes aegypti. Compared with earlier surveys in Germany, higher incidences occur and correlate well with ongoing outbreaks. Therefore, we investigated 767 serum samples from 594 returning travellers with suspected DF between 2005 and 2010, which where sent from different hospitals in the drainage area Frankfurt/Main. Established diagnostic assays were ELISA, immunofluorescence and chromatographic tests. We obtained 112 dengue-seropositive serum samples from totally 60 patients: the detection rate was 10.1% (60 out of 594). A significant increase was found in 2010. Most patients were aged between 40 and 49, and indirect immunofluorescence technique indicated mainly DF serotype 2. Actual data reveal a significant rise in imported DF cases in 2010 according to an increasing risk to acquire DF virus infection. Nevertheless, dengue haemorrhagic fever and dengue shock syndrome are still rare in travellers, but those with a history of dengue should be tested for DF serotypes and advised to protect themselves well from mosquitoes when travelling to endemic areas.

Do fewer cases of Kaposi's sarcoma in HIV-infected patients reflect a decrease in HHV8 seroprevalence?

Infection with human herpes virus 8 (HHV8) is associated with development of Kaposi's sarcoma (KS); therefore also known as KS-associated herpes virus. KS is closely associated with human immunodeficiency virus (HIV) infection, and consequently HHV8 seroprevalence is higher in HIV-infected compared to HIV-negative patients. Currently, KS is rarely seen in clinical practice, which might be a consequence of an optimized anti-HIV treatment leading to an improved immunological status, or alternatively of a decrease in HHV8 prevalence. To determine the prevalence of HHV8 antibodies in HIV-positive compared to HIV-negative patients from the University Hospital Frankfurt/Main, Germany, and to compare our results with previously published data to illustrate trends in the spread of infection. Hundred serum samples each of HIV-positive and HIV-negative patients were analyzed for HHV8 antibodies by using an IgG immunofluorescence test. The overall HHV8 seroprevalence was 16% with no statistically significant gender-specific differences; however, the distribution between the HIV-infected patients and the HIV-negative control group was significantly different (30 and 2%, respectively). The highest rate of seroprevalence in HIV-infected patients was detected at the age of 40-49 (42%) and the lowest rate at the age of 20-29 years (16.6%). In comparison with formerly conducted studies, our data clearly showed an increase in the HHV8 seroprevalence in HIV-infected patients, both in men and women. Therefore, we conclude that the low rate of clinical KS is associated with an improved immunological status due to an optimized anti-HIV therapy.

Prevalence- and gender-specific immune response to opportunistic infections in HIV-infected patients in Lesotho.

BACKGROUND: The objective of this study was to assess the seroprevalence of coinfecting viruses and Treponema pallidum (T. pallidum) in a cohort of 205 antiretrovirally treated HIV-infected individuals (152 females and 53 males, aged: 19-71 years) in rural Lesotho. Furthermore agent-specific immune responses were investigated by analyzing antibody titers against herpes simplex virus type 2 (HSV-2) and against T. pallidum. METHODS: Serum samples were tested by enzyme-linked immunosorbent assay for antibodies against HSV-2, cytomegalovirus, hepatitis A, B, and C viruses, and T. pallidum. RESULTS: Seroprevalences (95% confidence intervals) were found to be 100% (98.5%-100%) for anti-cytomegalovirus, 98.5% (95.7%-99.7%) for anti-hepatitis A virus, 35.5% (28.9%-42.6%) for anti-HBc, 5.5% (2.8%-9.6%) for hepatitis B surface antigen, and 0.5% (0.0%-2.8%) for anti-hepatitis C virus. Only 78.5% (72.2%-84.0%) were anti-HSV-2 positive and 29.0% (22.8%-35.8%) had antibodies against T. pallidum. Only anti-HSV-2 titers showed gender- and CD4 cell-count dependent differences: females with >500 CD4 cells/microL had an average anti-HSV-2 titer of 446 compared with males of 398 AU/mL (not significant), but in those with 250 to 500 CD4 cells/microL, there was a significant difference with a mean titer of 467 compared to 302 AU/mL in males (P = 0.001). CONCLUSIONS: A high seroprevalence of CMV, HAV, and HBV was found in both genders. One-third of the patients had been exposed to HBV and T. pallidum. The generally high HSV-2 prevalence showed gender- and CD4 cell count-dependent differences in HSV-2 antibody titer.

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.

Evaluation of the new ARCHITECT anti-HCV screening test under routine laboratory conditions.

BACKGROUND: An improved test version of the Abbott ARCHITECT anti-hepatitis C virus (HCV) test became available at the end of 2005. STUDY DESIGN: We compared the new test version with the Ortho Vitros anti-HCV test by evaluating 2034 serum samples in parallel on both systems under routine laboratory conditions. Discordant samples were tested in the Inno-LIA HCV Score assay as well as in the RIBA HCV 3.0. RESULTS: Of the 2034 samples 140 (6.9%) yielded positive and 1856 (91.2%) negative results in both assays. We observed discordant results in 38 samples (1.9%). All discrepant samples showed a low S/CO ratio of 1.0-6.9 (mean 2.8) in the Ortho assay and of 1.3-3.0 (mean 1.96) in the ARCHITECT assay. As expected, most of them could not be confirmed by immunoblot testing. Comparison of the results of the two immunoblots (Inno-LIA and RIBA) revealed a great variability in test results. CONCLUSIONS: This study represents the first comparative evaluation of the modified version of the Abbott ARCHITECT anti-HCV assay in comparison with the Ortho Vitros anti-HCV test. Under routine laboratory testing, we observed good overall concordance between the two assays and no evidence that one assay shows more false-reactive or negative results than the other.

Dengue in travellers is still underestimated.

BACKGROUND: Dengue fever (DF), one of the main emerging virus diseases, also increases in German travellers, due to the increasing number of travellers to tropical regions. METHODS: We determined antibodies against DF virus in a group (n = 149) of long-distance travellers in order to evaluate the risk of acquiring DF. Serum samples were collected at the travel vaccination centre in Frankfurt/Main and DF seroprevalence in serum samples was determined using different antibody assays with particular attention to flavivirus cross-reactivity. So, antibodies against tick-borne encephalitis and previous flavivirus vaccination of the travellers were checked. RESULTS: Depending on the test system, 8.7-19.5% of the screened travellers were found to be DF virus IgG antibody positive, significantly more than in previous investigations. Remarkably, younger adults and women are more often affected. CONCLUSIONS: These data imply that the risk for travellers to acquire DF has been underestimated. Nevertheless, dengue haemorrhagic fever and dengue shock syndrome are still rare in travellers, but those with a history of dengue should be advised to protect themselves well from mosquitoes when travelling to endemic areas.

Reliability of medical students' vaccination histories for immunisable diseases.

BACKGROUND: Medical students come into contact with infectious diseases early on their career. Immunity against vaccine-preventable diseases is therefore vital for both medical students and the patients with whom they come into contact. METHODS: The purpose of this study was to compare the medical history and serological status of selected vaccine-preventable diseases of medical students in Germany. RESULTS: The overall correlation between self-reported medical history statements and serological findings among the 150 students studied was 86.7 %, 66.7 %, 78 % and 93.3 % for measles, mumps, rubella and varicella, conditional on sufficient immunity being achieved after one vaccination. Although 81.2 % of the students' medical history data correlated with serological findings, significant gaps in immunity were found. CONCLUSION: Our findings indicate that medical history alone is not a reliable screening tool for immunity against the vaccine-preventable diseases studied.

[Viral gastroenteritis. An epidemiologic investigation between the period 2001-2006]. / Virale Gastroenteritiden. Eine epidemiologische Beobachtungsstudie im Zeitraum 2001-2006.

BACKGROUND: The most common causes for diarrhea both in children and adults are of viral genesis. Thereby rota-, noro-, adeno-, and astroviruses are mentioned in descending order. The diagnosis of these frequently nosocomial infections can easily result from virus antigen detection of stool samples. MATERIAL AND METHODS: In this retrospective epidemiologic survey of the number of annual stool samples of patients with gastroenteritis, the frequency scale of each virus as well as seasonal aspects, the genital arrangement, and age distribution of mainly patients of the University Hospital Frankfurt/Main and some other health institutions in the closer surrounding were analyzed during the period 2001-2006. RESULTS: The proficiency rate of viral investigations amounts to about 10-20%. Similar to previous years, the rotavirus infection poles the most frequent cause of infantile gastroenteritis in Germany. The second place is taken by another adeno- or by norovirus. Astrovirus infections have been seen more rarely in the last 3 years. CONCLUSION: In accordance with recent surveys in other regions it is shown that nowadays the main part of infectious gastroenteritis is caused by norovirus type 2 and--in opposition to rotavirus--elderly people are preferentially affected.

[How dangerous is avian flu for mankind?]. / Wie gefährlich ist die Vogelgrippe für den Menschen?

BACKGROUND: Avian influenza, an infectious disease of birds, is caused by type A strain 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. Various animals like birds, pigs, horses, sea mammals and, finally, humans are susceptible to influenza A viruses. The high possibility of genomic changes like gene shift and drift are caused by the segmented RNA genome. EPIDEMIOLOGY: Since December 2003 a total of eleven countries (Vietnam, Thailand, Indonesia, Cambodia, China, Laos, Japan, Malaysia, South Korea, Russia, Kazakhstan) have reported outbreaks of highly pathogenic avian influenza A (H5N1) virus affecting poultry. Mongolia reported detection of H5N1 virus in migratory birds in August 2005, and actually also Romania and Turkey. During the avian flu outbreak approximately 150 million birds have died or been culled. The virus also jumped to humans; a total of 117 H5N1 cases in humans have been reported to the WHO, in four countries (Vietnam, Thailand, Indonesia, and Cambodia), 60 patients of them died. That avian influenza could also be a threat to humans has been known since 1997. OUTLOOK: Because of the natural virus reservoir like wild and/or domesticated ducks and others, actually there is rarely no chance to eradicate influenza. Furthermore, the virus could mutate and jump to humans with the threat of a global influenza pandemic. However, this is a statistically rare event.

Differential loss of humoral immunity against measles, mumps, rubella and varicella-zoster virus in children treated for cancer.

BACKGROUND: Intensive chemotherapy in children with cancer results in long-term impairment of humoral immunity. Whereas most studies to date focused on children with acute lymphoblastic leukemia (ALL), little data have been published on patients suffering from Hodgkin disease or from solid tumors. We therefore analyzed the loss of protective immunity (defined as immunity at the time of diagnosis and lack of immunity after completion of therapy) against vaccine-preventable diseases in children treated for various malignancies. METHODS: Children and adolescents <21 years of age at diagnosis and treated between 2001 and 2010 for various malignancies in the Department of Pediatric Hematology and Oncology, University of Frankfurt, were included in the retrospective chart review. Antibody levels against measles, mumps, rubella and varicella-zoster-virus (VZV) were routinely assessed at the time of diagnosis and within 12 months after completion of therapy. RESULTS: The study population consisted of 195 children (122 male); 80 patients had ALL, 15 acute myelogenous leukemia (AML), 18 non-Hodgkin lymphoma (NHL), 22 Hodgkin disease, and 60 various solid tumors. Overall, 27%, 47%, 19%, and 17% of the patients lost their humoral immunity against measles, mumps, rubella, and VZV, respectively. The risk of losing protective antibody titers depended on age with a higher risk in younger children. The loss of protective humoral immunity occurred significantly more often in patients with ALL compared to patients with any other underlying malignant disease (hematological malignancies such AML and NHL, Hodgkin disease or solid tumors). CONCLUSIONS: Our data demonstrate that a significant number of children lose pre-existing humoral immunity against measles, mumps, rubella, and VZV after completion of chemotherapy. This loss occurs more often in children with ALL than in children with AML, solid tumors and Hodgkin disease. Our results underline the need for post-chemotherapy revaccination of childhood cancer survivors.