[Travel vaccinations in rheumatic diseases : Specific considerations in children and adults]. / Reiseimpfungen bei rheumatischen Erkrankungen : Besonderheiten bei Kindern und Erwachsenen.

Children and adults with rheumatic diseases (RD) have a higher risk to contract infections due to the underlying disease and the frequently necessary immunosuppressive treatment (IT). The quality of life of the majority of patients with RD has remarkably improved due to IT-related reduction of inflammation. Therefore, RD patients usually have an international travel behavior similar to healthy individuals. An investigation indicated that patients with RD and IT have lower travel vaccination rates and are often less well-prepared for their trip in comparison to healthy travelers, even when visiting high risk destinations. As the risk for general and travel-acquired infections is increased for patients with RD with and without IT, pretravel consultations are important. These pretravel consultations should include recommendations addressing travel cancellation, travel modification and travel vaccinations depending on the patient's risk. Travel vaccinations include vaccinations against hepatitis A, typhoid fever, rabies, cholera, meningococcal diseases, tick-bone encephalitis, Japanese encephalitis, seasonal influenza, poliomyelitis and yellow fever. In patients with RD the indications for vaccination depend on the exposure risks, disease severity, individual travel behavior, and possible complications associated with vaccination. In the further evaluation process it is crucial to include the general health condition of the patient, the underlying RD (type and activity), duration and intensity of the IT. In general, live-attenuated vaccines are contraindicated under IT. In contrast, inactivated vaccines may be administered although reduced immunogenicity with the need for antibody measurement, special vaccine schedules or additional booster vaccinations should be considered under IT.

A systematic review of varicella seroprevalence in European countries before universal childhood immunization: deriving incidence from seroprevalence data.

Surveillance systems for varicella in Europe are highly heterogeneous or completely absent. We estimated the varicella incidence based on seroprevalence data, as these data are largely available and not biased by under-reporting or underascertainment. We conducted a systematic literature search for varicella serological data in Europe prior to introduction of universal varicella immunization. Age-specific serological data were pooled by country and serological profiles estimated using the catalytic model with piecewise constant force of infection. From the estimated profiles, we derived the annual incidence of varicella infection (/100·000) for six age groups (<5, 5-9, 10-14, 15-19, 20-39 and 40-65 years). In total, 43 studies from 16 countries were identified. By the age of 15 years, over 90% of the population has been infected by varicella in all countries except for Greece (86·6%) and Italy (85·3%). Substantial variability across countries exists in the age-specific annual incidence of varicella primary infection among the <5 years old (from 7052 to 16 122 per 100 000) and 5-9 years old (from 3292 to 11 798 per 100 000). The apparent validity and robustness of our estimates highlight the importance of serological data for the characterization of varicella epidemiology, even in the absence of sampling or assay standardization.

The Swiss National Registry for Primary Immunodeficiencies: report on the first 6 years' activity from 2008 to 2014.

The Swiss National Registry for Primary Immunodeficiency Disorders (PID) was established in 2008, constituting a nationwide network of paediatric and adult departments involved in the care of patients with PID at university medical centres, affiliated teaching hospitals and medical institutions. The registry collects anonymized clinical and genetic information on PID patients and is set up within the framework of the European database for PID, run by the European Society of Immunodeficiency Diseases. To date, a total of 348 patients are registered in Switzerland, indicating an estimated minimal prevalence of 4·2 patients per 100 000 inhabitants. Distribution of different PID categories, age and gender are similar to the European cohort of currently 19 091 registered patients: 'predominantly antibody disorders' are the most common diseases observed (n = 217/348, 62%), followed by 'phagocytic disorders' (n = 31/348, 9%). As expected, 'predominantly antibody disorders' are more prevalent in adults than in children (78 versus 31%). Within this category, 'common variable immunodeficiency disorder' (CVID) is the most prevalent PID (n = 98/217, 45%), followed by 'other hypogammaglobulinaemias' (i.e. a group of non-classified hypogammaglobulinaemias) (n = 54/217, 25%). Among 'phagocytic disorders', 'chronic granulomatous disease' is the most prevalent PID (n = 27/31, 87%). The diagnostic delay between onset of symptoms and diagnosis is high, with a median of 6 years for CVID and more than 3 years for 'other hypogammaglobulinaemias'.

Gastrointestinal pathogens detected by multiplex nucleic acid amplification testing in stools of pediatric patients and patients returning from the tropics.

BACKGROUND: Gastrointestinal infections are caused by a broad spectrum of pathogens. Conventional diagnostic procedures are resource and time consuming due to single pathogen testing, often in different laboratories. METHOD: We analyzed 312 consecutive stool samples from pediatric patients (n = 127) with gastroenteritis or from adult travelers returning from the tropics with suspected parasite infestation (n = 185) using commercial multiplex nucleic acid amplification testing (NAT) (xTAG gastrointestinal pathogen panel, Luminex) covering 15 diarrhea-causing pathogens. The results of the positive samples and a representative number of negative samples were compared to standard methods, including NAT, direct antigen detection (DAD), bacterial culture and microscopy. RESULTS: Of the 185 samples from adult travelers, 21 (11 %) were multiplexNAT-positive, with enterotoxigenic Escherichia coli (4 %) being the predominant pathogen. Microscopic examination revealed Blastocystis hominis in 23 % not covered by the panel. MultiplexNAT scored positive in 66 pediatric samples (52 %), with rotavirus (27 %) being the most prevalent. All adenovirus-, rotavirus-, Clostridium difficile- and Cryptosporidium-positive samples were confirmed in external laboratories, but only 40 % of norovirus- and 29 % of Giardia-positive samples. Analysis of frozen specimens by bacterial culture showed the highest discrepancies with the multiplexNAT. CONCLUSION: Our study demonstrates broad detection of relevant gastroenteritis pathogens by multiplexNAT with a short turnaround time. This is important for diagnosis, infection control and empiric management of gastroenteritis patients, but may be selectively complemented by bacterial culture and resistance testing.

Rational diagnostic strategies for Lyme borreliosis in children and adolescents: recommendations by the Committee for Infectious Diseases and Vaccinations of the German Academy for Pediatrics and Adolescent Health.

The varying clinical manifestations of Lyme borreliosis, transmitted by Ixodes ricinus and caused by Borrelia burgdorferi, frequently pose diagnostic problems. Diagnostic strategies vary between early and late disease manifestations and usually include serological methods. Erythema migrans is pathognomonic and does not require any further laboratory investigations. In contrast, the diagnosis of neuroborreliosis requires the assessment of serum and cerebrospinal fluid. Lyme arthritis is diagnosed in the presence of newly recognized arthritis and high-titer serum IgG antibodies against B. burgdorferi. The committee concludes the following recommendations: Borrelial serology should only be ordered in case of well-founded clinical suspicion for Lyme borreliosis, i.e., manifestations compatible with the diagnosis. Tests for borrelial genomic sequences in ticks or lymphocyte proliferation assays should not be ordered. When results of such tests or of serological investigations that were not indicated are available, they should not influence therapeutic decisions. Laboratories should be cautious when interpreting results of serological tests and abstain from giving therapeutic recommendations and from proposing retesting after some time without intimate knowledge of patient's history and disease manifestations.

The respiratory pathology in infants with sudden unexpected deaths in whom respiratory specimens were initially PCR-positive or PCR-negative for Bordetella pertussis.

BACKGROUND: In a previous controlled study, we investigated the relationship between Bordetella pertussis infections and sudden unexpected deaths among German infants (sudden infant death syndrome, SIDS). In this present study, we investigated further the respiratory pathology in a subset of infants in the original study. METHODS: Originally, there were 234 infants with SIDS and, of these, 12 had either a nasopharyngeal swab (NPS) or a tracheal swab specimen (TS) that was positive for B. pertussis by polymerase chain reaction (PCR). Here, tissue specimens from eight infants who were originally PCR-positive were compared with tissue specimens from seven infants in whom the original PCR studies were negative. RESULTS: The histopathologic diagnoses were as follows: 14 of 15 had pulmonary edema and the remaining case had early diffuse alveolar damage. Although 14 of 15 cases had some histologic or clinical evidence suggesting respiratory tract infection, the features were more consistent with a viral etiology, and in none were the findings typical of respiratory disease attributable to B. pertussis. CONCLUSIONS: The findings in this present investigation do not support a direct role of B. pertussis at the site of infection (ciliated epithelium) in the causation of SIDS. The clinical aspects of this study were carried out in the 1990s when pertussis was widespread in Germany. Therefore, the original finding of some PCR-positive cases is not surprising. The possibility that B. pertussis infection could still be a factor in some SIDS cases, e.g., by a systemic release of toxins, cannot be definitely ruled out.

Assessment of varicella vaccine effectiveness in Germany: a time-series approach.

A multivariate time-series regression model was developed in order to describe the 2005-2008 age-specific time-course of varicella sentinel surveillance data following the introduction of a varicella childhood vaccination programme in Germany. This ecological approach allows the assessment of vaccine effectiveness under field conditions by relating vaccine coverage in cohorts of 24-month-old children to the mean number of cases per reporting unit in the sentinel network. For the 1-2 years age group, which is directly affected by the vaccination programme, a one-dose vaccine effectiveness of 83·2% (95% CI 80·2-85·7) was estimated which corresponds to previous approaches assessing varicella vaccine effectiveness in the field in the USA.

Lemierre syndrome and nosocomial transmission of Fusobacterium necrophorum from patient to physician.

BACKGROUND: Human-to-human transmission of Fusobacterium necrophorum has not been described before. CASE PRESENTATION: We present the case of a 15-year-old girl with Lemierre Syndrome and possible nosocomial transmission of F. necrophorum to her treating physician in hospital. CONCLUSION: Early diagnosis and treatment of anaerobic pharyngitis is critical to prevent Lemierre Syndrome. Respiratory precautions should be recommended to medical staff caring for patients with suspected Lemierre Syndrome to prevent nosocomial transmission.

Dose-dependent effectiveness of acellular pertussis vaccine in infants: A population-based case-control study.

BACKGROUND: Pertussis is a vaccine-preventable disease which is most severe in young infants. More than two decades after the introduction of acelluar pertussis vaccines (aPV) in national immunization programs in many countries worldwide, a resurgence of pertussis has been recognized. Suboptimal effectiveness of aPV has been blamed as one major reason but only few studies have evaluated dose-dependent vaccine effectiveness (VE) provided by aPV in current practice. METHODS: We performed a population-based retrospective case-control study by comparing pertussis immunization data of children 2.5 months to 2 years of age hospitalized for pertussis and residing in Switzerland with immunization data of a random control sample of children aged 2 years and residing in Switzerland. VE was defined as the percentage of hospitalizations avoided by number of aPV doses. It was calculated as 1-infection rate ratio (IRR)*100. IRR was calculated by dividing infection rates of vaccinated children and infection rates of unvaccinated children. To get dose specific VE,infection rates were stratified by number doses received. RESULTS: VE against hospitalization due to pertussis increased significantly with each consecutive aPV dose in a "3 + 1" primary course in infants: 42.1% (95% CI: 11.3-62.6), 83.9% (70.2-92.1), 98.2% (96.1-99.3), and 100% (97.9-100) after the 1st, 2nd, 3rd, and 4th dose, respectively. CONCLUSION: Acellular pertussis vaccines continue to demonstrate protection against hospitalization due to pertussis in infants and young children. Therefore, together with advancing immunization of pregnant women and household contacts, better control of severe pertussis in young infants can be achieved by timely initiation of immunization.

Child-parent immunization survey: How well are national immunization recommendations accepted by the target groups?

BACKGROUND: Pertussis disease rates are high in Switzerland, especially in infants and young infants. To protect newborns from this serious disease, EKIF, the Swiss National Immunization Technical Advisory Group, has recommended vaccination against pertussis during pregnancy (2nd or 3rd trimester) since 2013. Also, since 2009, EKIF has recommended vaccination against influenza during pregnancy.We conducted this study to assess acceptance and implementation of these recently introduced recommendations. METHODS: We performed standardized interviews with parents of children born on or after 01.01.2013, hospitalized at the University of Basel Children's Hospital, Switzerland, between January and June 2017. If participation was declined, partial consent was sought for four questions regarding age, education level, attitudes towards vaccinations in general and availability of vaccination records. RESULTS: In 193 of 398 eligible children the mother participated. Five (3%) of 172 mothers had received both pertussis and influenza vaccines during pregnancy, 15 (9%) only against pertussis and 12 (7%) only against influenza. Very few mothers had received vaccination recommendation during pregnancy: 17 (10%) for both pertussis and influenza and 15 (9%) each for pertussis and influenza only. Main reasons for refusal of vaccination despite recommendation were that they were not deemed useful (59% for influenza and 37% for pertussis) and safety concerns for the child (18% for influenza and 26% for pertussis). CONCLUSIONS: Recommendation for and immunization rates against pertussis and influenza during pregnancy are low and need to be improved. As recommendations from health care personnel have been shown to have the most significant impact on immunization rates, we propose to focus on improving awareness and acceptance for immunization in pregnancy among health care personnel involved in the care of pregnant women.

Prospective multinational serosurveillance study of Bordetella pertussis infection among 10- to 18-year-old Asian children and adolescents.

OBJECTIVES: Bordetella pertussis continues to cause outbreaks worldwide. To assess the role of children and adolescent in transmission of pertussis in Asia, we performed a multinational serosurveillance study. METHODS: From July 2013 to June 2016, individuals aged 10 to 18 years who had not received any pertussis-containing vaccine within the prior year were recruited in 10 centres in Asia. Serum anti-pertussis toxin (PT) IgG was measured by ELISA. Demographic data and medical histories were obtained. In the absence of pertussis immunization, anti-PT IgG ≥62.5 IU/mL was interpreted as B. pertussis infection within 12 months prior, among them levels ≥125 IU/mL were further identified as infection within 6 months. RESULTS: A total of 1802 individuals were enrolled. Anti-PT IgG geometric mean concentration was 4.5, and 87 (4.8%) individuals had levels ≥62.5 IU/mL; among them, 73 (83.9%) had received three or more doses of pertussis vaccine before age 6 years. Of 30 participants with persistent cough during the past 6 months, one (3.3%) had level ≥125 IU/mL. There was no significant difference in proportions with anti-PT IgG ≥62.5 IU/mL among age groups (13-15 vs. 10-12 years, 16-18 vs. 10-12 years), between types of diphtheria, pertussis and tetanus (DTP; whole cell vs. acellular), number of doses before age 6 years within the DTP whole-cell pertussis vaccine (five vs. four doses) or acellular pertussis vaccine (five vs. four doses) and history of persistent cough during the past 6 months (yes vs. no). CONCLUSIONS: There is significant circulation of B. pertussis amongst Asian children and adolescents, with one in 20 having serologic evidence of recent infection regardless of vaccination background.

[Influenza in children--an epidemiological problem]. / Influenza im Kindesalter--ein epidemiologisches Problem.

Influenza is an acute viral disease which mainly affects the respiratory tract and occurs in all age groups with yearly epidemics during the cold season. It is a frequent and occasionally severe disease in children, particularly in young infants and school age children with a high rate of complications (mainly secondary bacterial infections) which frequently require hospitalization. Children are usually the first victims of the yearly epidemics and effectively distribute the virus in the community and their families. These specific characteristics warrant discussions about modifications of the current immunization strategy in countries like Switzerland, where high risk individuals are the primary immunization targets. An universal influenza immunization strategy would be reasonable from an individual as well as epidemiological point of view. However, the need for repeated yearly vaccination as well as suboptimal acceptance of influenza immunization amongst physicians and the public are significant hurdles, which would need to be overcome.

Guide to active vaccine safety surveillance: Report of CIOMS working group on vaccine safety - executive summary.

In 2013, the Council for International Organizations of Medical Sciences (CIOMS) created a Working Group on Vaccine Safety (WG) to address unmet needs in the area of vaccine pharmacovigilance. Generating reliable data about specific vaccine safety concerns is becoming a priority due to recent progress in the development and deployment of new vaccines of global importance, as well as novel vaccines targeting diseases specifically endemic to many resource-limited countries (RLCs), e.g. malaria, dengue. The WG created a Guide to Active Vaccine Safety Surveillance (AVSS) to assist national regulatory authorities and national immunization program officers in RLCs in determining the best course of action with regards to non-routine pharmacovigilance activities, when confronted with a launch of a new vaccine or a vaccine that is new to their country. Here we summarize the results of the WG, further detailed in the Guide, which for the first time provides a structured approach to identifying and analyzing specific vaccines safety knowledge gaps, while considering all available sources of information, in order to determine whether AVSS is an appropriate solution. If AVSS is confirmed as being the appropriate tool, the Guide provides additional essential information on AVSS, a detailed overview of common types of AVSS and practical implementation considerations. It also provides a framework for a well-constructed and informative AVSS when needed, thus aiming to ensure the best possible safety of immunization in this new landscape.

Outbreak investigation for toxigenic Corynebacterium diphtheriae wound infections in refugees from Northeast Africa and Syria in Switzerland and Germany by whole genome sequencing.

Toxigenic Corynebacterium diphtheriae is an important and potentially fatal threat to patients and public health. During the current dramatic influx of refugees into Europe, our objective was to use whole genome sequencing for the characterization of a suspected outbreak of C. diphtheriae wound infections among refugees. After conventional culture, we identified C. diphtheriae using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and investigated toxigenicity by PCR. Whole genome sequencing was performed on a MiSeq Illumina with >70×coverage, 2×250 bp read length, and mapping against a reference genome. Twenty cases of cutaneous C. diphtheriae in refugees from East African countries and Syria identified between April and August 2015 were included. Patients presented with wound infections shortly after arrival in Switzerland and Germany. Toxin production was detected in 9/20 (45%) isolates. Whole genome sequencing-based typing revealed relatedness between isolates using neighbour-joining algorithms. We detected three separate clusters among epidemiologically related refugees. Although the isolates within a cluster showed strong relatedness, isolates differed by >50 nucleotide polymorphisms. Toxigenic C. diphtheriae associated wound infections are currently observed more frequently in Europe, due to refugees travelling under poor hygienic conditions. Close genetic relatedness of C. diphtheriae isolates from 20 refugees with wound infections indicates likely transmission between patients. However, the diversity within each cluster and phylogenetic time-tree analysis suggest that transmissions happened several months ago, most likely outside Europe. Whole genome sequencing offers the potential to describe outbreaks at very high resolution and is a helpful tool in infection tracking and identification of transmission routes.

Hepatitis B Postexposure Prophylaxis in Preterm and Low-Birth-Weight Infants.

Objective Recommendations for immunoprophylaxis in low-birth-weight (LBW) infants born to hepatitis B surface antigen (HBsAg)-positive mothers vary. We successfully immunized an HBsAg-exposed infant (birth weight: 400 g) and performed a literature review on the outcome of postexposure immunoprophylaxis in HBsAg-exposed preterm and LBW infants. Methods By use of PubMed we identified articles relevant to the topic. Studies were included if the intended vaccine schedule was completed and follow-up data were reported. Results Antibody response was reported in 31 LBW infants (birth weight < 2,500 g) and 49 infants with gestational age of < 38 weeks. Low anti-HBs antibody levels (< 100 IU/L) were found in 9 (29%) of the 31 LBW infants. Overall, 2 of 20 (10%) preterm infants and 2 of 17 (12%) LBW were HBsAg-positive on follow-up. In one study, none of the 26 exposed very LBW infants became infected. Conclusion Due to heterogeneity in immunization schedules, lack of information on transmission rates, and the small number of included subjects, no firm conclusions can be drawn regarding the optimal postexposure prophylaxis in LBW infants. We propose that active and passive immunization at birth should be completed by three further active doses (0-1-2-12 month schedule) until further prospective studies are available.

The effect of investigator compliance (observer bias) on calculated efficacy in a pertussis vaccine trial.

BACKGROUND: In the course of a large pertussis vaccine efficacy trial we realized that investigator compliance could have a major impact on calculated vaccine efficacy. DESIGN: In our pertussis vaccine efficacy trial, the study investigators were to monitor illness in study families by telephone every 2 weeks. If a cough illness of >/=7 days duration was noted, the study child was to be evaluated. If the cough illness persisted for >/=14 days, the child was to be referred to a central investigator. For this report we analyzed study physician evaluation rates and rates of referral to the central investigators. Physician practices were separated into three compliance categories: high, intermediate, and low. We analyzed vaccine efficacy of an acellular pertussis component DTP vaccine (DTaP) and a whole cell pertussis component DTP vaccine (DTP) by compliance category. Bordetella pertussis infection was documented by culture of the organism in the study child or in a household contact or by a significant antibody response to pertussis toxin determined by enzyme-linked immunosorbent assay. RESULTS: Using a clinical case definition that included both mild and typical pertussis (cough illness >/=7 days duration) efficacy of DTaP vaccine was 40% (95% confidence interval [CI] = -3-65) in the high compliance category and 78% (95% CI = 65-86) and 75% (95% CI = 53-87) in the intermediate and low compliance groups, respectively. Similar, but less marked, differences in efficacy were noted with DTP vaccine recipients. Using a clinical case definition that required >/=21 days of cough with paroxysms, whoop, or vomiting (typical pertussis) the efficacy of DTaP vaccine was 69% (95% CI = 41-83) in the high compliance category and 86% (95% CI = 76-92) and 84% (95% CI = 64-93) in the intermediate and low compliance groups, respectively. In contrast, the efficacy of DTP vaccine did not vary by compliance category using this case definition. The attack rate in children vaccinated with diphtheria and tetanus toxoids vaccine (DT) was twofold less in low compliance physician practices when compared with the rates in high and intermediate groups. The DT/DTaP and DT/DTP fold-change differences were less in the high compliance group compared with the intermediate and low compliance groups. CONCLUSIONS: Our data suggest that observer compliance (observer bias), can significantly inflate calculated vaccine efficacy. It is likely that all recently completed efficacy trials have been effected by this type of observer bias and all vaccines have considerably less efficacy against mild disease than published data suggest.