Cerebrospinal fluid CXCL13 as a diagnostic marker of neuroborreliosis in children: a retrospective case-control study.

BACKGROUND: Lyme neuroborreliosis (LNB) is a frequent manifestation of Lyme disease in children and its current diagnosis has limitations. The elevation of the chemokine CXCL13 in the cerebrospinal fluid (CSF) of adult patients with LNB has been demonstrated and suggested as a new diagnostic marker. Our aim was to evaluate this marker in the CSF of children with suspected LNB and to determine a CXCL13 cut-off concentration that would discriminate between LNB and other central nervous system (CNS) infections. METHODS: For this single-center retrospective case-control study we used a diagnostic-approved ELISA to measure CXCL13 concentrations in the CSF of 185 children with LNB suspicion at presentation. Patients were classified into definite LNB (cases), non-LNB (controls with other CNS affections), and possible LNB. A receiver-operating characteristic curve was generated by comparison of cases and controls. RESULTS: CXCL13 was significantly elevated in the CSF of 53 children with definite LNB (median 774.7 pg/ml) compared to 91 control patients (median 4.5 pg/ml, p < 0.001). A cut-off of 55 pg/ml resulted in a sensitivity of 96.7% and a specificity of 98.1% for the diagnosis of definite LNB and the test exhibited a diagnostic odds ratio of 1525.3. Elevated CSF CXCL13 levels were also detected in three controls with viral meningitis (enterovirus n = 1, varicella-zoster virus n = 2) while other CNS affections such as idiopathic facial palsy did not lead to CXCL13 elevation. Of the 41 patients with possible LNB, 27% had CXCL13 values above the cut-off of 55 pg/ml (median 16.7 pg/ml). CONCLUSIONS: CSF CXCL13 is highly elevated in children during early LNB as previously shown in adults. CXCL13 is a highly sensitive and specific marker that helps to differentiate LNB from other CNS affections in children.

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'.

Prospective population-based study of RSV-related intermediate care and intensive care unit admissions in Switzerland over a 4-year period (2001-2005).

OBJECTIVES: Respiratory syncytial virus (RSV) infections are a leading cause of hospital admissions in small children. A substantial proportion of these patients require medical and nursing care, which can only be provided in intermediate (IMC) or intensive care units (ICU). This article reports on all children aged < 3 years who required admission to IMC and/or ICU between October 1, 2001 and September 30, 2005 in Switzerland. PATIENTS AND METHODS: We prospectively collected data on all children aged < 3 years who were admitted to an IMC or ICU for an RSV-related illness. Using a detailed questionnaire, we collected information on risk factors, therapy requirements, length of stay in the IMC/ICU and hospital, and outcome. RESULTS: Of the 577 cases reported during the study period, 90 were excluded because the patients did not fulfill the inclusion criteria; data were incomplete in another 25 cases (5%). Therefore, a total of 462 verified cases were eligible for analysis. At the time of hospital admission, only 31 patients (11%) were older than 12 months. Since RSV infection was not the main reason for IMC/ICU admission in 52% of these patients, we chose to exclude this subgroup from further analyses. Among the 431 infants aged < 12 months, the majority (77%) were former near term or full term (NT/FT) infants with a gestational age > or = 35 weeks without additional risk factors who were hospitalized at a median age of 1.5 months. Gestational age (GA) < 32 weeks, moderate to severe bronchopulmonary dysplasia (BPD), and congenital heart disease (CHD) were all associated with a significant risk increase for IMC/ICU admission (relative risk 14, 56, and 10, for GA < or = 32 weeks, BPD, and CHD, respectively). Compared with NT/FT infants, high-risk infants were hospitalized at an older age (except for infants with CHD), required more invasive and longer respiratory support, and had longer stays in the IMC/ICU and hospital. CONCLUSIONS: In Switzerland, RSV infections lead to the IMC/ICU admission of approximately 1%-2% of each annual birth cohort. Although prematurity, BPD, and CHD are significant risk factors, non-pharmacological preventive strategies should not be restricted to these high-risk patients but also target young NT/FT infants since they constitute 77% of infants requiring IMC/ICU admission.

[Recurrent febrile episodes--normal, periodic fever syndrome or immunodeficiency?]. / Mein Kind ist immer krank--wann ist es wirklich krank? Vom periodischen Fiebersyndrom bis zum Immundefekt.

Fever is one of the main symptoms leading to medical evaluation. Not only infections cause fever but also inflammatory disorders. To distinguish one from another, a thorough medical history and clinical evaluation are needed. Sometimes, only the clinical course will reveal the diagnosis. PFAPA-Syndrome (periodic fever, aphthous stomatitis, pharyngitis, adenitis) is the most frequent periodic fever syndrome in Switzerland. No diagnostic test is available to support the diagnosis. Some important diseases have to be ruled out, such as Immunodeficiency, cyclic neutropenia, chronic viral infections and rheumatologic disorders. To know the diagnosis of the PFAPA-Syndrome can help avoiding antibiotic courses for febrile episodes in infants. There is a clinical overlap to hereditary periodic fever syndromes as familial Mediterranean fever (FMF), Hyper-IgD and fever syndrome (HIDS), Tumor-necrosis factor receptor associated periodic syndrome (TRAPS) and others, in which a genetic basis for the disease has already been found.

Regional impact of prophylaxis with the monoclonal antibody palivizumab on hospitalisations for respiratory syncytial virus in infants.

QUESTIONS: Palivizumab is approved in Switzerland for prevention of hospitalisation for RSV infection in children with one of the following risk factors: (1) history of prematurity < or = 35 weeks and age < or = 6 months or (2) chronic lung disease and age < or = 1 year. Regional data on the expected effectiveness of this monoclonal antibody are not available. METHODS: (1) Retrospective, descriptive, single-site study on the characteristics of RSV hospitalisations during two consecutive seasons. (2) Extrapolation of data to generate population-based estimates on the impact of palivizumb if used according to the approved indications. RESULTS: Of 242 RSV hospitalisations, 216 (89.3%) and 26 (10.7%) occurred in children without and with risk factors, respectively. Patients without and with risk factors had similar clinical courses with respect to ICU admission rate (11.6 vs. 11.5%) and rate of mechanical ventilation (3.2 vs. 3.8%). Of a total of 28 ICU admissions, 13 (46%) occurred among infants aged < or = 1 month without risk factors. Former premature infants were significantly older than patients with longer gestation (median age 7.5 vs. 3.7 months, p = 0.026). Applying the approved age criteria would have excluded 10 of 26 patients (38.5%) from eligibility for palivizumab. During the 1999/2000 RSV season, 36% of hospitalisations occurred after April 1, 2000. None of them may have been preventable had prophylaxis been started before November 1, 1999 and carried out for 5 months as recommended. In an annual birth cohort of 10,000, palivizumab as indicated would be expected to prevent between 5 and 7 RSV hospitalisations. CONCLUSIONS: The impact of palivizumab on the prevention of RSV hospitalisations in the Canton of Bern, Switerland, is expected to be small, and the approved indications may not target infants at greatest risk for severe disease.

[Viral encephalitis, early summer meningoencephalitis]. / Virale Enzephalitis, Frühsommer-Meningoenzephalitis (FSME).

Encephalitis is an unusual manifestation of viral infections. Encephalitis manifests with fever, headache and an altered level of consciousness. To identify an etiologic diagnosis, epidemiologic data (season, prevalent diseases, travel, exposure and animal contacts) may be helpful, whereas clinical findings mostly are nonspecific. The cerebrospinal fluid analysis shows a moderate pleocytosis with a slightly increased protein concentration. With PCR, the ability to diagnose CNS viral infections has improved, particularly for herpes simplex and enteroviral infections. Effective therapy is available only for a limited number of viral infections. Some cases of encephalitis can be reliably prevented by vaccination (measles, mumps, TBE, rabies). Tick-borne encephalitis (TBE), which is of particular interest in Switzerland, is described in detail.

[Antimicrobial resistance--consequences for ambulatory treatment of infections in children]. / Antimikrobielle Resistenzen--Konsequenzen für die ambulante Behandlung von Infektionskrankheiten bei Kindern.

Increasing antimicrobial resistance among clinical isolates of Streptococcus pneumoniae calls for a revision of treatment strategies for pediatric infections, particularly for acute otitis media. Restrictive use of antimicrobials is the key strategy for slowing the spread of resistances. Before initiation of antimicrobial therapy, suspected bacterial infections should be confirmed clinically (e.g. by observation of the natural evolution) or microbiologically. For acute otitis media, oral amoxicillin remains the drug of choice because of superior middle ear pharmacokinetics and pharmacodynamics. Treatment failure caused by resistance of the infecting pneumococcus can be overcome be increasing the dose, and not by switching to another class of antibiotics (e.g., cephalosporin, macrolide, cotrimoxazole), which is less likely to achieve middle ear eradication a priori. Widespread macrolide resistance among isolates of S. pneumoniae precludes the use of this class of antimicrobials for empiric therapy of community-acquired pneumonia in children. Aminopenicillins are preferred because of their rapidly bactericidal activity against the most common organisms causing potentially progressive pneumonia in children.

[Recurrent febrile episodes in childhood. From immunodeficiency to normality]. / Infektanfälligkeit im Kindesalter--wie weiter? Vom primären Immundefekt zum periodischen Fiebersyndrom.

Fever is one of the leading symptom in childhood diseases. If there are recurrent febrile episodes, one have to distinguish between recurrent infections in the normal age range, periodic fever syndromes or even a primary immunodeficiency. Diagnostic tools to distinguish one from another are reported. The warning signs for primary immunodeficiency are listed and discussed. For periodic fever syndromes, the PFAPA syndrome, the most frequent in Swiss children, is discussed in some detail.

Myopericarditis associated with central European tick-borne encephalitis.

UNLABELLED: The case of an 11-year-old child with acute myopericarditis associated with central European tick-borne encephalitis is presented. Cardiac involvement was demonstrated by pericardial effusion, elevated serum concentration of troponin-I and cardiac arrhythmia. Co-infections with enteroviruses, Borrelia burgdorferi or the agent of human granulocytic ehrlichiosis were excluded. Recovery was uneventful. CONCLUSION: Central European tick-borne encephalitis can be complicated by cardiac involvement.

Two-year periodicity of respiratory syncytial virus epidemics in Switzerland.

BACKGROUND: The annual respiratory syncytial virus (RSV) epidemics vary in time and severity. The aims of this study were (1) to describe the time-related pattern of RSV epidemics in Switzerland and (2) to deduce the most effective time period for administration of prophylactic measures to high-risk patients. PATIENTS AND METHODS: Descriptive study of (1) RSV hospitalizations between 1997 and 2001 at a pediatric hospital serving a population of 1 million and (2) of national RSV detection rates reported by diagnostic laboratories between 1988 and 1999. RESULTS: 497 RSV hospitalizations and 8,574 reported RSV detections occurring during four and 12 epidemics, respectively, were analyzed. There was fixed alternation of minor and major epidemics differing in the number of RSV infections (two to fourfold), evolution (median interval from onset to peak 13 weeks, range 4-13 weeks vs 8 weeks, range 7-10 weeks; p = 0.065) and median duration (26 weeks, range 24-29 weeks vs 19.5 weeks, range 18-21 weeks; p = 0.005). For minor epidemics it was estimated that a maximum of 85.6% (range, 79.4-86.6%) of annual RSV infections could be covered by a standard five-dose regimen of the monoclonal anti-RSV antibody palivizumab, if initiated in week 50. During major epidemics the most effective time of initiation would be week 43 (88.7%; range 81.9-94.6%). CONCLUSION: RSV epidemiology in Switzerland is characterized by fixed biannual variation. In the absence of active RSV surveillance, such periodicity is useful for scheduling RSV prophylaxis and for hospital resources management.

Influenza-associated myositis in children.

BACKGROUND: Influenza-associated myositis (IAM) is an infrequent and poorly known complication of influenza virus infection in children. The aim of this study was to describe five cases of IAM and to review the literature on IAM in children. PATIENTS AND METHODS: We conducted a retrospective analysis of cases of IAM diagnosed at two university children's hospitals in Switzerland during two consecutive influenza seasons. Findings were compared with 39 individual case reports and five publications summarizing an additional 272 cases identified by a medical online library (MEDLINE) search. RESULTS: Overall, 316 cases were analyzed. IAM typically occurred in school-aged children with a 2:1 male predominance. Influenza B and A viruses were identified in 76% and 24% of cases, respectively. The median interval between onset of influenza and onset of IAM was 3 days (range 0-18). The calf muscles were involved alone or together with other muscle groups in 69% and 31% of cases, respectively. Blood creatine phosphokinase (CPK) concentration was invariably elevated. Median duration to clinical recovery was 3 days (range 1-30). Rhabdomyolysis occurred in ten of 316 patients (3%), was more common in girls (80%), more often associated with influenza A (86%), and led to renal failure in eight patients (80%). CONCLUSION: Clinical and laboratory findings of IAM are highly characteristic and allow a rapid diagnosis during the influenza season.

Low incidence of respiratory syncytial virus hospitalisations in haemodynamically significant congenital heart disease.

BACKGROUND: Haemodynamically significant congenital heart disease (CHD) is a risk factor for severe respiratory syncytial virus (RSV) disease in young children. Population based data on the incidence of RSV hospitalisations in CHD patients are needed to estimate the potential usefulness of RSV immunoprophylaxis using palivizumab. AIMS: (1) To obtain population based RSV hospitalisation rates in children <24 months of age with CHD. (2) To compare these rates with non-CHD patients and with previous studies. (3) To determine the number of patients needed to treat (NNT) with palivizumab to prevent one RSV hospitalisation. METHODS: Six year, longitudinal, population based study at an institution, which is the sole provider of primary to tertiary in-patient care for a precisely defined paediatric population. RESULTS: RSV hospitalisation rates (per 100 child-years) in CHD patients aged <6, <12, 12-24, and <24 months of age were 2.5 (95% CI 0.8 to 5.6), 2.0 (0.8 to 3.8), 0.5 (0.1 to 1.8), and 1.3 (0.6 to 2.3), respectively, and the relative risk (RR) in comparison with non-CHD patients was 1.4 (0.6 to 3.1), 1.6 (0.8 to 3.2), 2.7 (0.7 to 9.7), and 1.8 (1.0 to 3.3), respectively. NNT was between 80 (35 to 245) and 259 (72 to 2140) for various age groups. CONCLUSION: RSV hospitalisation rates in CHD patients were fourfold lower than reported from the USA. Based on these low rates and RR, unrestricted use of palivizumab does not appear to be justified in this study area.