Acellular Pertussis Booster in Adolescents Induces Th1 and Memory CD8+ T Cell Immune Response

In a number of countries, whole cell pertussis vaccines (wcP) were replaced by acellular vaccines (aP) due to an improved reactogenicity profile. Pertussis immunization leads to specific antibody production with the help of CD4+ T cells. In earlier studies in infants and young children, wcP vaccines selectively induced a Th1 dominated immune response, whereas aP vaccines led to a Th2 biased response. To obtain data on Th1 or Th2 dominance of the immune response in adolescents receiving an aP booster immunization after a wcP or aP primary immunization, we analyzed the concentration of Th1 (IL-2, TNF-α, INF-γ) and Th2 (IL-4, IL-5, IL-10) cytokines in supernatants of lymphocyte cultures specifically stimulated with pertussis antigens. We also investigated the presence of cytotoxic T cell responses against the facultative intracellular bacterium Bordetella pertussis by quantifying pertussis-specific CD8+ T cell activation following the aP booster immunization. Here we show that the adolescent aP booster vaccination predominantly leads to a Th1 immune response based on IFNgamma secretion upon stimulation with pertussis antigen, irrespective of a prior whole cell or acellular primary vaccination. The vaccination also induces an increase in peripheral CD8+CD69+ activated pertussis-specific memory T cells four weeks after vaccination. The Th1 bias of this immune response could play a role for the decreased local reactogenicity of this adolescent aP booster immunization when compared to the preceding childhood acellular pertussis booster. Pertussis-specific CD8+ memory T cells may contribute to protection against clinical pertussis

Varicella-zoster virus infections in immunocompromised patients - a single centre 6-years analysis

Background: Infection with varicella-zoster virus (VZV) contemporaneously with malignant disease or immunosuppression represents a particular challenge and requires individualized decisions and treatment. Although the increasing use of varicella-vaccines in the general population and rapid initiation of VZVimmunoglobulins and acyclovir in case of exposure has been beneficial for some patients, immunocompromised individuals are still at risk for unfavourable courses. Methods: In this single center, 6-year analysis we review incidence, hospitalization and complication rates of VZVinfections in our center and compare them to published data. Furthermore, we report three instructive cases. Results: Hospitalization rate of referred children with VZV-infections was 45%, among these 17% with malignancies and 9% under immunosuppressive therapy. Rate of complications was not elevated in these two high-risk cohorts, but one ALL-patient died due to VZV-related complications. We report one 4-year old boy with initial diagnosis of acute lymphoblastic leukemia who showed a rapidly fatal outcome of his simultaneous varicella-infection, one 1.8-year old boy with an identical situation but a mild course of his disease, and an 8.5-year old boy with a steroiddependent nephrotic syndrome. This boy developed severe hepatic involvement during his varicella-infection but responded to immediate withdrawl of steroids and administration of acyclovir plus single-dose cidofovir after nonresponse to acyclovir after 48 h. Conclusion: Our data show that patients with malignant diseases or immunosuppressive therapy should be hospitalized and treated immediately with antiviral agents. Despite these measures the course of VZV-infections can be highly variable in these patients. We discuss aids to individual decision-making for these difficult situations

Live Attenuated B. pertussis as a Single-Dose Nasal Vaccine against Whooping Cough

Pertussis is still among the principal causes of death worldwide, and its incidence is increasing even in countries with high vaccine coverage. Although all age groups are susceptible, it is most severe in infants too young to be protected by currently available vaccines. To induce strong protective immunity in neonates, we have developed BPZE1, a live attenuated Bordetella pertussis strain to be given as a single-dose nasal vaccine in early life. BPZE1 was developed by the genetic inactivation or removal of three major toxins. In mice, BPZE1 was highly attenuated, yet able to colonize the respiratory tract and to induce strong protective immunity after a single nasal administration. Protection against B. pertussis was comparable to that induced by two injections of acellular vaccine (aPV) in adult mice, but was significantly better than two administrations of aPV in infant mice. Moreover, BPZE1 protected against Bordetella parapertussis infection, whereas aPV did not. BPZE1 is thus an attractive vaccine candidate to protect against whooping cough by nasal, needle-free administration early in life, possibly at birth

P67-phox (NCF2) Lacking Exons 11 and 12 Is Functionally Active and Leads to an Extremely Late Diagnosis of Chronic Granulomatous Disease (CGD)

Two brothers in their fifties presented with a medical history of suspected fungal allergy, allergic bronchopulmonary aspergillosis, alveolitis, and invasive aspergillosis and pulmonary fistula, respectively. Eventually, after a delay of 50 years, chronic granulomatous disease (CGD) was diagnosed in the index patient. We found a new splice mutation in the NCF2 (p67-phox) gene, c.1000+2T→G, that led to several splice products one of which lacked exons 11 and 12. This deletion was in frame and allowed for remarkable residual NADPH oxidase activity as determined by transduction experiments using a retroviral vector. We conclude that p67-phox which lacks the 34 amino acids encoded by the two exons can still exert considerable functional activity. This activity can partially explain the long-term survival of the patients without adequate diagnosis and treatment, but could not prevent progressing lung damage

Hospitalization due to varicella in the Netherlands

<p>Abstract</p> <p>Background</p> <p>In the Netherlands, incidence of physician's consultations and hospitalizations for varicella is low compared to other countries. Better knowledge about the severity of varicella among Dutch hospitalized patients is needed. Therefore, a medical record research was conducted among hospitalized patients with diagnosis varicella.</p> <p>Methods</p> <p>Hospital admissions due to varicella in 2003-2006 were obtained from the National Medical Register. Retrospectively, additional data were retrieved from the medical record of patients hospitalized with varicella in 23 Dutch hospitals using a standardized form. Analyses were performed using descriptive statistics.</p> <p>Results</p> <p>The study population (N = 296) was representative for all varicella admissions in the Netherlands (N = 1,658) regarding age, sex, duration of admission and type of diagnosis. Complications were recorded in 76% of the patients (37% had at least one relatively severe complication). Bacterial super infections of skin lesions (28%), (imminent) dehydration (19%), febrile convulsions (7%), pneumonia (7%) and gastroenteritis (7%) were most frequently reported. No varicella-related death occurred within the study population and 3% of the patients had serious rest symptoms.</p> <p>Conclusions</p> <p>It is not likely that the severity of varicella among hospitalized patients in the Netherlands differs from other countries. A considerable part of the varicella complications among hospitalized patients was rather moderate and can be treated effectively, although in a third of the hospitalized cases with complications, severe complications occurred. These data are relevant in the decision-making process regarding whether or not to introduce routine varicella vaccination in the Netherlands.</p

Defining the timing of respiratory syncytial virus (RSV) outbreaks: an epidemiological study

BACKGROUND: Seasonal RSV infections occur every year and affect particularly children under six months of age. Passive immunoprophylaxis with monoclonal antibody Palivizumab is recommended in the period with high risk of RSV infection. This study aims to define the period for the southern part of Germany (Stuttgart area). METHODS: Epidemiological analysis of the RSV situation in southern Germany from 1996 to 2004 and comparison of results with literature was made. The respiratory tract specimens were sent in for the detection of RSV mainly by paediatric clinics. Detection of RSV was carried out mainly by real-time RT-PCR or by ELISA "Pathfinder". RSV outbreaks were depicted as an absolute number and as a percentage of RSV diagnoses in a month. Onsets, offsets, peaks, duration and severity of RSV seasons were defined and analysed. RESULTS: An early season with strong RSV activity (early-high phase) was followed by a weaker late season (late-low phase) in a regular biennial rhythm. However, onsets, offsets and durations of outbreaks varied significantly from year to year. RSV epidemics in southern Germany were found to oscillate in an antiphase with RSV epidemics in Finland and Sweden. CONCLUSION: The long-term regular biennial rhythm allows predicting whether the next outbreak will be late or early and whether RSV activity will be strong or weak. Not foreseeable, however, is the precise time of increase and decrease of RSV activity. Moreover, the regular seasonal pattern may be disrupted by irregular outbreaks. Thus, activity of RSV has to be monitored every year to define the period with high risk of infection

An unusual cause of granulomatous disease

BACKGROUND: Chronic granulomatous disease (CGD) is an inherited disorder of phagocytic cells caused by an inability to generate active microbicidal oxygen species required kill certain types of fungi and bacteria. This leads to recurrent life-threatening bacterial and fungal infections with tissue granuloma formation. CASE PRESENTATION: We describe a case of X-linked Chronic granulomatous disease (CGD) diagnosed in an 18-year-old male. He initially presented with granulomatous disease mimicking sarcoidosis and was treated with corticosteroids. He subsequently developed Burkholderia cepacia complex pneumonia and further investigation confirmed a diagnosis of CGD. CONCLUSION: Milder phenotypes of CGD are now being recognised. CGD should be considered in patients of any age with granulomatous diseases, especially if there is a history of recurrent or atypical infection

Frequency of medically attended adverse events following tetanus and diphtheria toxoid vaccine in adolescents and young adults: a Vaccine Safety Datalink study

<p>Abstract</p> <p>Background</p> <p>Local reactions are the most commonly reported adverse events following tetanus and diphtheria toxoid (Td) vaccine and the risk of local reactions may increase with number of prior Td vaccinations.</p> <p>Methods</p> <p>To estimate the risk of medically attended local reactions following Td vaccination in adolescents and young adults we conducted a six-year retrospective cohort study assessing 436,828 Td vaccinations given to persons 9 through 25 years of age in the Vaccine Safety Datalink population from 1999 through 2004.</p> <p>Results</p> <p>Overall, the estimated risk of a medically attended local reaction was 3.6 events per 10,000 Td vaccinations. The lowest risk (2.8 events per 10,000 vaccinations) was found in the 11 to 15 year old age group. In comparison with that group, the event risks were significantly higher in both the 9 to 10 and 21 to 25 year old age groups. The risk of a local reaction was significantly higher in persons who had received another tetanus and diphtheria toxoid containing vaccine (TDCV) in the previous five years (incidence rate ratio, 2.9; 95% confidence interval, 1.2 to 7.2). Twenty-eight percent of persons with a local reaction to Td vaccine were prescribed antibiotics.</p> <p>Conclusion</p> <p>Medically attended local reactions were uncommon following Td vaccination. The risk of those reactions varied by age and by prior receipt of TDCVs. These findings provide a point of reference for future evaluations of the safety profile of newer vaccines containing tetanus or diphtheria toxoid.</p

Higher Doses of Subcutaneous IgG Reduce Resource Utilization in Patients with Primary Immunodeficiency

The recommended dose of IgG in primary immunodeficiency (PID) has been increasing since its first use. This study aimed to determine if higher subcutaneous IgG doses resulted in improved patient outcomes by comparing results from two parallel clinical studies with similar design. One patient cohort received subcutaneous IgG doses that were 1.5 times higher than their previous intravenous doses (mean 213 mg/kg/week), whereas the other cohort received doses identical to previous subcutaneous or intravenous doses (mean 120 mg/kg/week). While neither cohort had any serious infections, the cohort maintained on higher mean IgG dose had significantly lower rates of non-serious infections (2.76 vs. 5.18 episodes/year, P < 0.0001), hospitalization (0.20 vs. 3.48 days/year, P < 0.0001), antibiotic use (48.50 vs. 72.75 days/year, P < 0.001), and missed work/school activity (2.10 vs. 8.00 days/year, P < 0.001). The higher-dose cohort had lower health care utilization and improved indices of well being compared to the cohort treated with traditional IgG doses

The burden of varicella from a parent's perspective and its societal impact in The Netherlands: an Internet survey

<p>Abstract</p> <p>Background</p> <p>Varicella is a common childhood disease. Only 5% of first varicella-zoster-virus infections occur asymptomatically. Most data on the burden of varicella stem from health service databases. This study aims to provide insight in the burden of varicella from a parent's perspective including cases outside the healthcare system.</p> <p>Methods</p> <p>An internet questionnaire was developed for parents in the Netherlands to report health care resource use and productivity losses during the varicella episode in their child younger than 6 years. 11,367 invitations were sent out to members with children of an internet panel of a market research agency. 4,168 (37%) parents started the questionnaire (response rate), of which 360 (9%) stopped before completion and 1,838 (44%) were out of the target group. In total 1,970 parents completed the questionnaire. The questionnaire provided a symptom list ranging from common symptoms, such as skin vesicles, itching to fits or convulsions. A posteriori, in the analyses, the symptoms 'skin infections', 'fits/convulsions', 'unconsciousness', and 'balance and movement disorders' were labelled as complications. There was no restriction to time since the varicella episode for inclusion in the analyses.</p> <p>Results</p> <p>The 1,970 respondents had in total 2,899 children aged younger than six years, of which 2,564 (88%) children had had varicella. In 62% of the episodes the parent did not seek medical help. In 18% of all episodes symptoms labelled as complications were reported; in 11% of all episodes parents visited a medical doctor (MD) for a complication. Reporting of complications did not differ (X²; p = 0.964) between children with a recent (≤ 12 months ago) or a more distant (> 12 months) history of varicella. Prescription drugs were used in 12% of the children with varicella; OTC drugs in 72%. Parents reported work loss in 17% of the varicella-episodes (23% when MD visit; 14% when no MD-visit) for on average 14 hours, which equals to 2.5 hours of work loss for any given varicella-episode.</p> <p>Conclusions</p> <p>This study shows the full spectrum of varicella-episodes and associated healthcare use, including the large proportion of cases not seeking medical care and the societal impact associated with those cases.</p