Long-term persistence of seroprotection against measles following measles-mumps-rubella vaccination administered before and after pediatric liver transplantation.

Liver transplant (LT) recipients are susceptible to infections, including measles. Concerns about the safety and efficacy of live-attenuated vaccines, such as the measles-mumps-rubella (MMR) vaccine, have led to hesitancy among providers in administering them to immunocompromised patients. This 9-year interventional study assessed seroprotection against measles following MMR vaccination in pediatric LT recipients. Of 119 participants enrolled, 60 (50%) were seroprotected against measles after transplantation. Among the 59 non-seroprotected participants, 56 fulfilled safety criteria and received MMR vaccination with a seroprotection rate of 90% (95%CI 73-98%) after a first dose, 95% (95%CI 85-99%) after primary vaccination with 1 to 3 doses, comparable to non-immunocompromised populations. However, measles antibodies declined over time, suggesting the need for regular monitoring, and booster doses. Half of the vaccinees (26/53, 49%) subsequently lost seroprotection. Among them, 23 received additional doses of MMR, with high seroconversion rate. At their last follow up (median 6.1 years, IQR 3.0-8.1 after inclusion), 63% (95%CI 49-75%) of all vaccinees were seroprotected against measles. In conclusion, MMR vaccination in pediatric LT recipients offers seroprotection against measles, but long-term immunity should be monitored closely. CLINICAL TRIAL REGISTRATION: The trial is registered at the US National Institutes of Health (Clinicaltrials.gov) number NCT01770119.

Risk of Vaccine-Preventable Infections in Swiss Adults with Inflammatory Bowel Disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have a higher risk of infection and are frequently not up to date with their immunizations. OBJECTIVES: This study aims to review vaccination status and evaluate whether age, disease type, or treatment regimen could predict the absence of seroprotection against selected vaccine-preventable infection in adults with IBD. METHODS: Cross-sectional study using questionnaire, immunization records review, and assessment of tetanus-specific, varicella-specific, and measles-specific immunoglobulin G concentrations. ClinicalTrials.gov: NCT01908283. RESULTS: Among the 306 adults assessed (median age 42.7 years old, 70% with Crohn's disease, 78% receiving immunosuppressive treatment), only 33% had an immunization record available. Absence of seroprotection against tetanus (6%) was associated with increasing age and absence of booster dose; absence of seroprotection against varicella (1%) or measles (3%) was exclusively observed in younger patients with Crohn's disease. There was no statistically significant difference in immunoglobulin concentrations among treatment groups. Although vaccinations are strongly recommended in IBD patients, the frequencies of participants with at least 1 dose of vaccine recorded were low for nearly all antigens: tetanus 94%, diphtheria 87%, pertussis 54%, poliovirus 22%, measles-mumps-rubella 47%, varicella-zoster 0%, Streptococcus pneumoniae 5%, Neisseria meningitidis 12%, hepatitis A 41%, hepatitis B 48%, human papillomavirus 5%, and tick-borne encephalitis 6%. CONCLUSIONS: Although many guidelines recommend the vaccination of IBD patients, disease prevention through immunization is still often overlooked, including in Switzerland, increasing their risk of vaccine-preventable diseases. Serological testing should be standardized to monitor patients' protection during follow-up as immunity may wane faster in this population.

Multimodal safety assessment of measles-mumps-rubella vaccination after pediatric liver transplantation.

Live-attenuated vaccines are currently contraindicated in solid-organ transplant recipients. However, the risk of vaccine-preventable infections is lifelong, and can be particularly severe after transplantation. In this prospective interventional national cohort study, 44 pediatric liver transplant recipients with measles IgG antibodies <150 IU/L (below seroprotection threshold) received measles-mumps-rubella vaccine (MMR) at a median of 6.3 years posttransplantation (interquartile range, 4.0 to 10.9). A maximum of two additional doses were administered in nonresponders or when seroprotection was lost. Vaccine responses occurred in 98% (95% confidence interval [CI], 88-100) of patients. Seroprotection at 1-, 2-, and 3-year follow-up reached 62% (95% CI, 45-78), 86% (95% CI, 70-95), and 89% (95% CI, 67-99), respectively. All patients responded appropriately to the booster dose(s). Vaccinations were well tolerated and no serious adverse event attributable to vaccination was identified during the 8-week follow-up period (or later), using a multimodal approach including standardized telephone interviews, diarized side effect reporting, and monitoring of vaccinal virus shedding. We conclude that live attenuated MMR vaccine can be administered in liver transplant recipients fulfilling specific eligibility criteria (>1 year posttransplantation, low immunosuppression, lymphocyte count ≥0.75 G/L), inducing seroprotection in most subjects. (Clinicaltrials.gov number NCT01770119).

High Immunogenicity of the Pneumococcal Conjugated Vaccine in Immunocompromised Adults With Inflammatory Bowel Disease.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are predisposed to pneumococcal infections due to their underlying disease and iatrogenic immunosuppression. Vaccination with the 13-valent pneumococcal conjugated vaccine (PCV13) is recommended, but with poor take-up and few data available. We performed an open-label, phase IV, multicenter study to evaluate the safety and immunogenicity of PCV13 in adults with IBD and to analyze the influence of immunomodulating treatments on anti-pneumococcal seroresponses. METHODS: We enrolled 306 patients with IBD from March 2014 through February 2016, with the following exclusion criteria: current IBD flare, pregnancy, pneumococcal immunization in the previous 5 years, and influenza immunization in the previous 4 weeks. PCV13 was administered intramuscularly. Serotype-specific vaccine responses were evaluated using an opsonophagocytic assay. Adverse events were monitored by diary cards and standardized phone interviews. RESULTS: The median seroprotection rate increased significantly from 43.9% (95% confidence interval [CI], 42.3-45.5) at inclusion to 90.4% (95% CI, 89.5-91.3%; P < 0.001) after vaccination. Patients receiving anti-tumor necrosis factor agents achieved a slightly lower seroprotection rate (from 44.5% [95% CI, 42.3%-46.8%] to 86.6% [95% CI, 84.9%-88.1%]) than patients treated with other types of immunosuppressive regimens (thiopurine, methotrexate, oral corticosteroids; from 44.7% [95% CI, 41.7%-47.7%] to 93.8% [95% CI, 92.1%-95.2%]) or nonimmunosuppressive treatment (5-aminosalicylate, topical corticosteroids, vedolizumab; from 41.3% [95% CI, 37.9%-44.8%] to 95.2% [95% CI, 93.4%-96.6%]). There were no safety issues. DISCUSSION: Overall, the administration of PCV13 was highly immunogenic and well tolerated, irrespective of the baseline treatment, and should be encouraged in all adults with IBD.

Complications of indwelling central venous catheters in pediatric liver transplant recipients.

In pLT recipients, the advantages of ICVCs need to be weighed against the risk of complications. This single-center retrospective study aimed to review ICVC complications in our cohort of pLT recipients. We performed chart reviews of pLT patients having undergone transplant between 01/2000 and 03/2014 and who underwent ICVC placement either before or after LT. We identified 100 ICVC in 85 patients. Overall observation time was 90 470 catheter-days. There was no difference in catheter lifespan between those inserted pre- or post-transplant; 46% of ICVC presented a complication. Most frequent complications were MD and infection. The infection rate was 0.09 per 1000 catheter-days, and MD rate was 0.36 per 1000 catheter-days. Patients having received technical variant grafts were more at risk of complications. To the best of our knowledge, this is the first study examining ICVC complications in pLT recipients. We conclude that ICVC have a high rate of MD. Children receiving technical variants may be more at risk of complications. By removing ICVC in a select number of patients at six months post-insertion, we might avoid as much as 60% of complications.

[Antibiotics to treat streptococcal pharyngitis in Swiss children: is it still useful?]. / Antibiotiques pour traiter la pharyngite à streptocoque chez les enfants en Suisse: est-ce encore utile?

Group A Streptococcus (GAS) pharyngitis is a common pediatric infectious disease in school-aged children. After the detection of the bacteria in the pharynx, treatment with 10 days of antibiotics is recommended in Switzerland. The rationale to treat is based on studies from the 1950s, when the epidemiology of GAS strain was very different and the incidence of acute rheumatic fever significantly higher than today in developed countries. This article explores the current national recommendations, as well as the benefits of antibiotic treatment in the management of this infection. A reevaluation, as in other countries, of the management and treatment of GAS pharyngitis in Switzerland is considered.

Lipodystrophy among HIV-infected patients: a cross-sectional study on impact on quality of life and mental health disorders.

BACKGROUND: Lipodystrophy (LD) is a frequent adverse event of combination antiretroviral therapy (ART) and occurs mainly in patients exposed to first-generation antiretroviral drugs. The aim of this study was to explore and measure the interaction between LD, mental health, and quality of life of human immunodeficiency virus (HIV) positive individuals seen in a metabolic clinic. METHODS: We conducted a single-site cross-sectional study including all HIV-infected patients attending the LIPO group and metabolism day clinic at the University Hospitals of Geneva, Switzerland between January 31, 2008 and November 28, 2013. Data on LD were prospectively collected using the HIV Outpatient Study (HOPS) score, the Lipodystrophy Case Definition (LDCD), ART regimens, anthropometric measures, imaging, and standardized questionnaires. Quality of life was evaluated using a visual analog scale of 0-100. Depression and anxiety were assessed using the Beck Depression Inventory and the State Trait Anxiety Inventory scales, respectively. RESULTS: One hundred ninety-four patients (54.6% male; 45.4% female; median age, 50 years) on successful ART (median CD4 cell count, 569.0 cells/mm(3); median viral load, 20 copies/mL) were evaluated. Among these, 62.7, 63.5 and 35.5% of patients reported at least one body site affected by fat hypertrophy, atrophy or both, respectively. Using the LDCD score conservative definition, including imaging and biological values, 57.8% were diagnosed with LD. Of these, 39.7% suffered from severe/very severe LD. Depression was reported by 35.6% of individuals; 51.9% had anxiety symptoms and 49.5% reported poor quality of life (defined as being inferior to 50% on a scale from 0 to 100%). LD (odds ratio (OR = 5.22, 95% confidence interval (CI) 1.07-25.37, p-value: 0.040), depression (OR = 4.67, 95% CI 1.08-20.31, p-value 0.040), and anxiety (OR = 7.83, 95% CI 1.91-32.03, p-value 0.004) all affected significantly the quality of life. CONCLUSIONS: LD, depression and anxiety were frequent features among HIV-infected individuals seen in the metabolic clinic and significantly impacted on their quality of life.

Long-term Seroprotection of Varicella-zoster Immunization in Pediatric Liver Transplant Recipients.

BACKGROUND: Chickenpox is a highly contagious vaccine-preventable disease that can lead to severe complications, especially in immunocompromised patients. Varicella-zoster virus (VZV) vaccine appears to be safe and immunogenic in pediatric solid organ transplant recipients, but there are few data on the long-term vaccine-induced seroprotection. METHODS: In this prospective interventional study, we offered 2 doses of VZV vaccine to all eligible and nonseroprotected children seen 1 year after liver transplant. Vaccine responses were measured 1 month later and yearly thereafter. Vaccine safety was closely monitored. A supplementary dose was administered if protective levels were not reached/maintained. RESULTS: Among 121 enrolled patients, 49 were vaccinated and followed during 5.5 years (interquartile range, 3.7-8.0). Their seroconversion rate reached 100% (97.5% confidence interval [CI], 92.7-100). Low VZV-antibody concentration (≤400 UI/L) after the first 1-2 dose/s was associated with the need for a supplementary dose (odds ratio, 15.0; 95% CI, 3.4-67.0, P = 0.001) and was given to 31% (15/47) of children at 1.1 year (interquartile range, 0.9-3.9). Although antibody concentrations declined during follow-up, 96% (95% CI, 86.0-99.5) of patients maintained protective antibody concentrations at a median of 5.5 years after vaccination. One breakthrough disease was identified. CONCLUSIONS: VZV immunization of pediatric solid organ transplant recipients confers sustained seroprotection.

Toll-Interleukin 1 Receptor Domain-Containing Adaptor Protein 180L Single-Nucleotide Polymorphism Is Associated With Susceptibility to Recurrent Pneumococcal Lower Respiratory Tract Infections in Children.

Lower respiratory tract infections (LRTI) are often caused by Streptococcus pneumoniae (Spn) and can be recurrent in 8% of children older than 2 years of age. Spn is recognized by pattern-recognition receptors (PRRs) of the innate immune system, in particular toll-like receptors (TLRs) 2 and 4. To assess whether a defect somewhere along this TLR signaling pathway increases susceptibility to recurrent pneumococcal LRTI, we conducted a prospective case-control study with 88 healthy individuals and 45 children with recurrent LRTI aged 2-5 years old. We examined cell surface expression of TLR2 and TLR4, as well as eight genetic variants of these receptors or associated co-receptors TLR1 and TLR6. Interleukin-6 production was measured after whole blood stimulation assays with specific agonists and heat-killed Spn. Our findings reveal that single-nucleotide polymorphisms within toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP) alone or in combination with TLR1 N248S, TLR1 I602S, or TLR6 S249P polymorphisms contributes to various degree of susceptibility to recurrent pneumococcal LRTI in children by modulating the inflammatory response. In that respect, carriage of the TIRAP S180L heterozygous trait increases the likelihood to protect against pneumococcal LRTI, whereas children carrying the mutant homozygous TIRAP 180L polymorphism might be more likely susceptible to recurrent pneumococcal LRTI.

Live virus vaccines in transplantation: friend or foe?

Solid organ and hematopoietic stem cell transplant recipients may be exposed to diseases which may be prevented through live attenuated virus vaccines (LAVV). Because of their immunosuppression, these diseases can lead to severe complications in transplant recipients. Despite increasing evidence regarding the safety and effectiveness of certain LAVV, these vaccines are still contraindicated for immunocompromised patients, such as transplant recipients. We review the available studies on LAVV, such as varicella zoster, measles-mumps-rubella, influenza, yellow fever, polio, and Japanese encephalitis vaccines in transplant patients. We discuss the current recommendations and the potential risks, as well as the expected benefits of LAVV immunization in this population.

Lipohypertrophy and metabolic disorders in HIV patients on antiretroviral therapy: a systematic multidisciplinary clinical approach.

INTRODUCTION: Morphological and metabolic complications in HIV patients on antiretroviral therapy remain a challenge. While new cases of lipoatrophy (LA) disappear, irreducible central lipohypertrophy (LH) and metabolic complications require highly specialized management. We described a day hospital dedicated to lipodystrophy (LD) and metabolic disorders in HIV patients on treatment in Geneva, Switzerland, with a focus on LH. MATERIALS AND METHODS: The "Groupe Lipo & Metabolism" is a multidisciplinary consultation where patients undergo a standard evaluation including questionnaire, physical examination, dual-energy x-ray absorptiometry (DEXA) and L5-level CT scans, blood tests and consultations with various specialists. Based on prospectively maintained data, we describe clinical, biological and radiological characteristics of patients ≥18 years who attended the consultation between 2008 and 2013. We defined LH by CT scan, the gold standard method, as abdominal visceral adipose tissue (VAT) ≥130 cm(2), value associated with increased risk of cardiovascular event. RESULTS: A total of 195 patients attended the consultation during study period. Reasons for referral included LH in 28.3%, LA in 25% and mixed syndrome in 15.5% of cases. Metabolic disorders accounted for 19% of referrals with or without LD features. Among patients with a CT scan performed (n=183), 46 (25%) had LH with a VAT ≥130 cm(2). In this population, mean age was 49.1 years and 53.6% were male. HIV viral load was <50 cp/ml in 87% of patients. Mean body mass index was 24.6 kg/m(2). Mean waist to hip ratio (WHR) was 0.98 for males and 0.89 for females. A total of 9.8%, 29.5% and 35% of patients had abnormal levels of total cholesterol (≥6.5 mmol/L), triglycerides (≥2.0 mmol/L) and HDL cholesterol (≤1.0 mmol/L), respectively. Mean fasting glycaemia was 5.7 mmol/L and HbA1c was >6% in 10.5% of patients. Vitamin-D level was <75 nmol/L in 70.7% of patients. Respectively 31.2% and 12.1% of patients had osteopenia and osteoporosis on the spine and 44.8% and 6.6% on the hip neck. Factors associated with a VAT≥130 cm(2) included male gender (OR 3.7 [95% CI 1.7-8.2] p<0.001), triglycerides ≥2 mmol/L (OR 2.6 [95% CI 1.3-5.4] P<0.01) and increase in BMI category (OR 1.8 [95% CI 1.2-2.8] p<0.01). CONCLUSIONS: Lipohypertrophy is a prevalent feature of fat redistribution among HIV patients on treatment. Risk factors for LH include male gender, dyslipidemia and overweight. Glucose impairment and bone disorders are also common. A multidisciplinary approach is important to identify and promptly address these disorders. Acknowledgments: The "Groupe Lipo & Metabolism" team.