Klara M. Posfay-Barbe

Infection control in paediatrics

Infection control has a particularly important role in paediatric hospitals and must take into account the specificity of the needs and environment of the paediatric patient. Children are susceptible to infections that are prevented in older patients by vaccination or previous natural exposure. Consequently, the nosocomial pathogens and most common health-care-associated infection sites in children differ from those observed among adults. The immunological naivety of young children, especially neonates, translates into an enhanced susceptibility to many infections with important health consequences as well as higher rates and longer duration of microorganism shedding. In particular, respiratory virus infections, rotavirus, varicella zoster virus, and pertussis represent persistent challenges in childrens hospitals. Specific factors such as the use of breastmilk, toys, or therapy animals are associated with an increased risk for health-care-associated infections. We review the emergence of antimicrobial-resistant organisms and strategies to prevent health-care-associated infections in the paediatric setting.

Impact of synthetic and biologic disease‐modifying antirheumatic drugs on antibody responses to the AS03‐adjuvanted pandemic influenza vaccine: A prospective, open‐label, parallel‐cohort, single‐center study

OBJECTIVE To identify the determinants of antibody responses to adjuvanted split influenza A (H1N1) vaccines in patients with inflammatory rheumatic diseases. METHODS One hundred seventy-three patients (82 with rheumatoid arthritis, 45 with spondylarthritis, and 46 with other inflammatory rheumatic diseases) and 138 control subjects were enrolled in this prospective single-center study. Controls received 1 dose of adjuvanted influenza A/09/H1N1 vaccine, and patients received 2 doses of the vaccine. Antibody responses were measured by hemagglutination inhibition assay before and 3-4 weeks after each dose. Geometric mean titers (GMTs) and rates of seroprotection (GMT≥40) were calculated. A comprehensive medical questionnaire was used to identify the determinants of vaccine responses and adverse events. RESULTS Baseline influenza A/09/H1N1 antibody levels were low in patients and controls (seroprotection rates 14.8% and 14.2%, respectively). A significant response to dose 1 was observed in both groups. However, the GMT and the seroprotection rate remained significantly lower in patients (GMT 146 versus 340, seroprotection rate 74.6% versus 87%; both P<0.001). The second dose markedly increased antibody titers in patients, with achievement of a similar GMT and seroprotection rate as elicited with a single dose in healthy controls. By multivariate regression analysis, increasing age, use of disease-modifying antirheumatic drugs (DMARDs) (except hydroxychloroquine and sulfasalazine), and recent (within 3 months) B cell depletion treatment were identified as the main determinants of vaccine responses; tumor necrosis factor α antagonist treatment was not identified as a major determinant. Immunization was well tolerated, without any adverse effect on disease activity. CONCLUSION DMARDs exert distinct influences on influenza vaccine responses in patients with inflammatory rheumatic diseases. Two doses of adjuvanted vaccine were necessary and sufficient to elicit responses in patients similar to those achieved with 1 dose in healthy controls.

Development of a New Chlamydiales-Specific Real-Time PCR and Its Application to Respiratory Clinical Samples

ABSTRACT Originally composed of the single family Chlamydiaceae, the Chlamydiales order has extended considerably over the last several decades. Chlamydia-related bacteria were added and classified into six different families and family-level lineages: the Criblamydiaceae, Parachlamydiaceae, Piscichlamydiaceae, Rhabdochlamydiaceae, Simkaniaceae, and Waddliaceae. While several members of the Chlamydiaceae family are known pathogens, recent studies showed diverse associations of Chlamydia-related bacteria with human and animal infections. Some of these latter bacteria might be of medical importance since, given their ability to replicate in free-living amoebae, they may also replicate efficiently in other phagocytic cells, including cells of the innate immune system. Thus, a new Chlamydiales-specific real-time PCR targeting the conserved 16S rRNA gene was developed. This new molecular tool can detect at least five DNA copies and show very high specificity without cross-amplification from other bacterial clade DNA. The new PCR was validated with 128 clinical samples positive or negative for Chlamydia trachomatis or C. pneumoniae. Of 65 positive samples, 61 (93.8%) were found to be positive with the new PCR. The four discordant samples, retested with the original test, were determined to be negative or below detection limits. Then, the new PCR was applied to 422 nasopharyngeal swabs taken from children with or without pneumonia; a total of 48 (11.4%) samples were determined to be positive, and 45 of these were successfully sequenced. The majority of the sequences corresponded to Chlamydia-related bacteria and especially to members of the Parachlamydiaceae family.

Development of a real-time PCR for the specific detection of Waddlia chondrophila in clinical samples.

Waddlia chondrophila is considered as an emerging human pathogen likely involved in miscarriage and lower respiratory tract infections. Given the low sensitivity of cell culture to recover such an obligate intracellular bacteria, molecular-based diagnostic approaches are warranted. We thus developed a real-time PCR that amplifies Waddlia chondrophila DNA. Specific primers and probe were selected to target the 16S rRNA gene. The PCR specifically amplified W. chondrophila but did not amplify other related-bacteria such as Parachlamydia acanthamoebae, Simkania negevensis and Chlamydia pneumoniae. The PCR exhibited a good intra-run and inter-run reproducibility and a sensitivity of less than ten copies of the positive control. This real-time PCR was then applied to 32 nasopharyngeal aspirates taken from children with bronchiolitis not due to respiratory syncytial virus (RSV). Three samples revealed to be Waddlia positive, suggesting a possible role of this Chlamydia-related bacteria in this setting.

New Diagnostic Real-Time PCR for Specific Detection of Parachlamydia acanthamoebae DNA in Clinical Samples

ABSTRACT Given the low sensitivity of amoebal coculture, we developed a specific real-time PCR for the detection of Parachlamydia. The analytical sensitivity was high, and the inter- and intrarun variabilities were low. When the PCR was applied to nasopharyngeal aspirates, it was positive for six patients with bronchiolitis. Future studies should assess the role of Parachlamydia in bronchiolitis.

How Do Physicians Immunize Their Own Children? Differences Among Pediatricians and Nonpediatricians

Context. Immunization has an essential impact on public health worldwide. Numerous studies have shown the efficacy of different vaccines to protect individuals from various diseases. However, some parents choose not to vaccinate their children for reasons such as, among others, doubts regarding their usefulness, concerns over safety or efficacy, etc. Physicians are known to exert a direct influence on immunization rates by answering questions and clarifying misconceptions. Yet, it is unknown how they immunize their own children. Objective. We sought to assess how physicians interested in vaccination issues immunized, or would immunize, their own children. Design, Setting, and Participants. An 11-question, Web- based survey with a total of 102 discrete answers was sent to 2070 Swiss physicians in October 2004. All physicians were subscribers to a nonprofit, Web-based expert network (InfoVac, www.infovac.ch) that distributes monthly newsletters and answers question within 2 days on immunization issues. The InfoVac network reaches >95% of pediatricians in Switzerland but <20% of general practitioners. All responses were anonymous, and no identifier could be used to trace the participants of the survey. Questions were divided into 2 parts: (1) physicians who were parents were asked which vaccines they gave to their own children and at what age, and (2) all physicians were asked which vaccines they would give to their own child and at what age if they had a newborn child in 2004. Vaccines available in Switzerland at the time of the survey were offered as possible replies, and recommended vaccines were considered as those noted in the Swiss federal immunization schedule issued yearly. One question compared their immunization practice between their own children and their patients. Sociodemographics, qualifying year, membership in different professional groups, and their type of practice were also requested. Statistics. Standard descriptive statistics were used for sociodemographic characteristics. Univariate statistical analyses were performed for each variable to determine its relationship to the dependent variable, being a pediatrician or nonpediatrician. Logistic-regression analysis was used to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs), controlling for any statistically significant demographic variables that might function as confounders (gender, parenthood, workplace, year of diploma, and type of practice). For all statistical tests, differences were considered significant at P < .05. Main Outcome Measure. We performed a comparison of past and projected immunization rates in the children of pediatricians and nonpediatricians. Results. One thousand seventeen valid questionnaires were received (response rate: 49.1%; pediatricians: 53.3%). Nine hundred fifteen physicians (90%) had ≥1 child. All physicians reported immunizing children in their practice. Pediatricians were more likely to be women and to work in private practice than nonpediatricians but less likely to belong to a self-reported alternative medicine association. Among the nonpediatricians, 317 were general practitioners, 144 were internists, and 95 were other specialists. Ninety-two percent of pediatricians followed the official immunization recommendations for their own children. In contrast, after controlling for gender, workplace, type of practice, and year of diploma, nonpediatricians were more likely not to have immunized their children against measles, mumps, hepatitis B, or Haemophilus influenzae type b. They more frequently postponed diphtheria-tetanus-pertussis (DTP) (OR: 4.5; 95% CI: 2.0–10.19) and measles-mumps-rubella (MMR) vaccination. Although projected immunization rates were higher than effective rates, 10% of nonpediatricians would still not follow the official immunization recommendations in 2004. They would more frequently refrain from using combination vaccines and postpone DTP and MMR immunization to later in life. Several comparisons confirmed the weaker use of the more recently licensed vaccines by nonpediatricians. In addition to vaccines currently recommended in Switzerland, both groups of physicians added hepatitis A, influenza, and varicella vaccines to the vaccination schedule of their own children. Pediatricians were more likely to give pneumococcal (OR: 2.26; 95% CI: 1.004–4.68) and meningococcal C (OR: 2.26; 95% CI: 1.62–3.17) vaccines to their own children. In contrast, they were less likely to give tick-borne encephalitis virus vaccine (OR: 0.65; 95% CI: 0.44–0.95). Conclusions. Ninety-three percent of the surveyed physicians agree with the current official vaccination recommendations and would apply them to their own children. However, the observation that 5% of nonpediatricians would not use Haemophilus influenzae type b vaccine if they had a child born in 2004 is unexpected and concerning. In contrast, both groups gave additional vaccines than those recommended to their own children. Among physicians in Switzerland interested in immunization, a significant proportion of nonpediatricians decline or delay the immunization of their own children with the recommended MMR- or DTP-based combination vaccines, which indicates that clarification of misconceptions such as fear of “immune overload” has not yet reached important targets among health care providers who thus are unlikely to answer parental concerns adequately.

Varicella‐Zoster Immunization in Pediatric Liver Transplant Recipients: Safe and Immunogenic

Varicella can have a severe course in immunosuppressed patients. Although prevention is fundamental, live‐attenuated varicella‐zoster (VZV) vaccine is not currently recommended in transplant recipients. Our aims were to (1) evaluate VZV immunity in pediatric liver transplant (LT) recipients; (2) immunize (two doses) seronegative patients post‐LT; (3) monitor vaccine safety, (4) assess B and T cell vaccine responses. All patients followed at the Swiss National Pediatric LT Center were approached and 77/79 (97.5%) were enrolled (median age 7.8 years). Vaccine safety was monitored by standardized diary cards and phone calls. VZV‐specific serology and CD4+ T cells were assessed before and after immunization. Thirty‐nine patients (51.1%) were seronegative including 14 children immunized pre‐LT. Thirty‐six of 39 seronegative patients were immunized post‐LT (median 3.0 years post LT). Local (54.8%) and systemic (64.5%) reactions were mild and transient. The frequency of VZV‐specific CD4+ T cells and antibody titers increased significantly (respectively from 0.085% to 0.16%, p = 0.04 and 21.0 to 1134.5 IU/L, p < 0.001). All children reached seroprotective titers and 31/32 (97%) patients assessed remained seroprotected at follow‐up (median 1.7 years). No breakthrough disease was reported during follow‐up (median 4.1 years). Thereby, VZV vaccine appears to be safe, immunogenic and provide protection against disease in pediatric LT patients.

Prevalence of nosocomial infections in Swiss children's hospitals

OBJECTIVE To acquire data on pediatric nosocomial infections (NIs), which are associated with substantial morbidity and mortality and for which data are scarce. DESIGN Prevalence survey and evaluation of a new comorbidity index. SETTING Seven Swiss pediatric hospitals. PATIENTS Those hospitalized for at least 24 hours in a medical, surgical, intensive care, or intermediate care ward. RESULTS Thirty-five NIs were observed among 520 patients (6.7%; range per hospital, 1.4% to 11.8%). Bacteremia was most frequent (2.5 per 100 patients), followed by urinary tract infection (1.3 per 100 patients) and surgical-site infection (1.1 per 100 patients; 3.2 per 100 patients undergoing surgery). The median duration until the onset of infection was 19 days. Independent risk factors for NI were age between 1 and 12 months, a comorbidity score of 2 or greater, and a urinary catheter. Among surgical patients, an American Society of Anesthesiologists (ASA) score of 2 or greater was associated with any type of NI (P = .03). Enterobacteriaceae were the most frequent cause of NI, followed by coagulase-negative staphylococci; viruses were rarely the cause. CONCLUSIONS This national prevalence survey yielded valuable information about the rate and risk factors of pediatric NI. A new comorbidity score showed promising performance. ASA score may be a predictor of NI. The season in which a prevalence survey is conducted must be considered, as this determines whether seasonal viral infections are observed. Periodic prevalence surveys are a simple and cost-effective method for assessing NI and comparing rates among pediatric hospitals.

Food poisoning as a cause of acute liver failure.

We report a 9-year-old girl with cereulide-producing Bacillus cereus food poisoning, who developed fulminant hepatitis, renal and pancreatic insufficiency, shock, and prolonged seizures. She was transferred to our institution for hepatic transplantation before her diagnosis was established. As a result of rapid identification of the microorganism and supportive care, liver transplantation was avoided, and she recovered fully.

Bordetella holmesii: an under-recognised Bordetella species

Bordetella holmesii, first described in 1995, is believed to cause both invasive infections (bacteraemia, meningitis, endocarditis, pericarditis, pneumonia, and arthritis) and pertussis-like symptoms. Infection with B holmesii is frequently misidentified as being with B pertussis, the cause of whooping cough, because routine diagnostic tests for pertussis are not species-specific. In this Review, we summarise knowledge about B holmesii diagnosis and treatment, and assess research needs. Although no fatal cases of B holmesii have been reported, associated invasive infections can cause substantial morbidities, even in previously healthy individuals. Antimicrobial treatment can be problematic because B holmesiis susceptibility to macrolides (used empirically to treat B pertussis) and third-generation cephalosporins (often used to treat invasive infections) is lower than would be expected. B holmesiis adaptation to human beings is continuing, and virulence might increase, causing the need for better diagnostic assays and epidemiological surveillance.