Safety and Immunogenicity of Live Viral Vaccines in a Multicenter Cohort of Pediatric Transplant Recipients.

Importance: Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. Objective: To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. Design, Setting, and Participants: This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. Exposures: Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. Main Outcome and Measure: Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. Results: The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. Conclusions and Relevance: The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.

Oral Step-Down Therapy With Levofloxacin for Febrile Neutropenia in Children With Cancer.

BACKGROUND: Although febrile neutropenia (FN) is a frequent complication in children with cancer receiving chemotherapy, there remains significant variability in selection of route (intravenous [IV] vs oral) and length of therapy. We implemented a guideline with a goal to change practice from using IV antibiotics after hospital discharge to the use of step-down oral therapy with levofloxacin for most children with FN until absolute neutrophil count > 500. The objectives of this study were to determine the impact of this guideline on home IV antibiotic use, and to evaluate the safety of implementation of this guideline. METHODS: We performed a quasi-experimental, pre-post study of discharge FN treatment at a stand-alone children's hospital in patients without bacteremia discharged between January 2013 and October 2018. In January 2015, a multidisciplinary team created a guideline to switch most children with FN to oral levofloxacin, which was formally implemented as of September 2017. Discharges during the postintervention period (after September 2017) were compared to discharges in the preintervention period (between January 2013 and December 2014). RESULTS: In adjusted multivariable regression analyses, the postimplementation period was associated with a decrease in home IV antibiotics (adjusted risk ratio [aRR], 0.07 [95% confidence interval {CI}, .03-.13]) and fewer IV antibiotic initiations within 24 hours of a new healthcare encounter up to 7 days after discharge (aRR, 0.39 [95% CI, .17-.93]) compared to the preintervention time period. CONCLUSIONS: Step-down oral levofloxacin for children with FN who are afebrile with an ANC ≤ 500 at discharge is feasible and resulted in similar clinical outcomes compared to home IV antibiotics.

The First Case of Trypanosoma cruzi-Associated Retinitis in an Immunocompromised Host Diagnosed With Pan-Organism Polymerase Chain Reaction.

We report the first case of Trypanosoma cruzi-associated retinitis diagnosed using 28s ribosomal DNA sequencing. The case highlights the utility of broad-range molecular diagnostics for detecting rare and unsuspected ocular pathogens. Ocular involvement in Chagas disease is also discussed.

Risk of herpes zoster in children with asthma.

BACKGROUND: There is literature that indicates the association of asthma with an increased risk of common and serious microbial infections. We recently reported an increased risk of vaccine-preventable diseases, e.g., herpes zoster (HZ) among children with asthma, defined by predetermined asthma criteria. Little is known about whether this association is persistent if the asthma status is defined by different asthma criteria, e.g., the Asthma Predictive Index, given the heterogeneity of asthma. OBJECTIVE: To assess the consistency of the association between asthma and the risk of HZ in children. METHODS: This is a population-based case-control study based on all pediatric patients with HZ between 1996 and 2001 in Olmsted County, Minnesota, and 1:1 age- and sex-matched controls without a history of HZ who were enrolled in our previous study. The original Asthma Predictive Index criteria was operationalized by two or more wheezing episodes in a year for the first 3 years of life plus one of the major (physician-diagnosed asthma for a parent or physician-diagnosed eczema for a patient) or two of the minor criteria (physician-diagnosed allergic rhinitis for a patient, wheezing apart from cold, or eosinophilia [≥4%]). Data were fit to traditional logistic regression models to calculate odds ratios and 95% confident intervals. RESULTS: Of the original cohort (n = 554), 95 (17%) did not meet the enrollment criteria for this study, which left 459. Of the 221 patients, 53% were female, with a mean (standard deviation) age of 9.7 ± 4.2 years. The risk of HZ was increased in children with asthma defined by the API controlling for a varicella vaccine history and atopic status (adjusted odds ratio 2.56 [95% confidence interval, 1.08-6.56]). CONCLUSIONS: The association between asthma and increased risk of HZ in children and adolescents is consistent, independent of asthma definitions. Asthma might be an important clinical condition to be considered in HZ vaccine studies.

Atopic conditions other than asthma and risk of the 2009 novel H1N1 infection in children: a case-control study.

A recent study showed an increased risk of 2009 novel H1N1 influenza (H1N1) infection among asthmatic children. Little is known whether this is true for other atopic conditions. This study was designed to determine the association between atopic dermatitis and/or allergic rhinitis and the risk of H1N1 infection among children. We conducted a case-control study in Olmsted County, MN. We randomly selected children ≤18 years of age with a positive test for H1N1. Controls were randomly selected from a pool of residents with negative H1N1 tests and were matched to cases with regard to birthday, gender, clinic registration date, diagnostic test, and month of influenza testing using frequency matching. We compared the frequency of atopic conditions other than asthma between cases and their matched controls. We enrolled 168 cases and 172 controls. Among cases, 91 (54.2%) were male patients, and 106 (63.1%) were white. The median age of cases was 6.3 years (interquartile range, 3.1-11.5). Among cases, 79 (47.0%) had atopic dermatitis and/or allergic rhinitis diagnosed before or after the index date, whereas 54 (31.4%) controls had such conditions (odds ratio [OR], 1.89; 95% CI, 1.15-3.12; p = 0.012, adjusting for asthma status, 2008-2009 seasonal influenza vaccine, time of illness at index date, and other comorbid conditions). History of receiving 2008-2009 seasonal influenza vaccine was associated with H1N1 infection (adjusted OR, 2.06; 95% CI, 1.32-3.28; p = 0.002). Our results suggest an association between H1N1 infection and atopic conditions other than asthma. The association between 2008-2009 seasonal influenza vaccinations and the risk of H1N1 requires further investigation.

Asthma and severity of 2009 novel H1N1 influenza: a population-based case-control study.

BACKGROUND: Asthma has been shown to be associated with an increased risk of the 2009 novel H1N1 influenza (H1N1) infection among children. However, little is known about the role of asthma in severity of H1N1 infection. OBJECTIVE: To determine the association between asthma and other atopic conditions and severity of H1N1 infection. PATIENTS AND METHODS: We conducted a population-based case-control study. Cases were all Olmsted County, MN residents admitted to the hospital within a week of a positive test for H1N1. Controls who had a positive H1N1 but were not admitted to hospital were individually matched to cases with regard to birth day, gender, clinic registration date, diagnostic method, and calendar month of influenza testing. Asthma was ascertained using predetermined criteria. Data were fit to conditional logistic regression models. RESULTS: There were 46 eligible individuals admitted to hospitals with H1N1 infection during the study period. Ninety-seven controls were individually matched to their corresponding cases. Among cases, 23 (50%) were male and 29 (63.0%) were Caucasians. The median age at hospitalization was 20.7 years. Twenty-five (54.4%) cases had asthma before the date of hospitalization, compared to 33 (34.0%) controls (matched OR: 2.31; 95% CI, 1.13-4.73; p = 0.02). This association approached statistical significance after adjusting for all pertinent covariates (adjusted matched OR: 2.55; 95% CI, 0.98-6.64; p = 0.055). CONCLUSION: Asthma may be associated with severe H1N1 infection. In addition to timely influenza vaccination for asthmatics, consideration for prophylactic treatment for unimmunized asthmatics with significant exposure to influenza and immunized asthmatics with early flu-like symptoms should be given.

Increased risk of herpes zoster in children with asthma: a population-based case-control study.

OBJECTIVE: To determine the risk of herpes zoster (HZ) in children with and without asthma. STUDY DESIGN: This study was designed as a population-based case-control study. We examined all children (aged <18 years) with possible HZ in Olmsted County, Minnesota, between 1996 and 2001 (n = 306; identified by International Classification of Diseases, Eighth Revision codes and predetermined criteria for HZ) to identify true cases. To determine the association between asthma and HZ, we compared the frequency of asthma among children with HZ with that among age- and sex-matched corresponding controls (1:1 matching) who resided in Olmsted County, Minnesota, during the study period. Asthma was ascertained based on predetermined criteria. A conditional logistic regression model was used to calculate ORs and 95% CIs. RESULTS: We identified 277 eligible patients with HZ, 63 (23%) of whom had a history of asthma before the index date of HZ, compared with 35 of 277 (12.6%) matched controls (aOR, 2.09; 95% CI, 1.24-3.52; P = .006), adjusting for varicella vaccination and atopy status. The population-attributable risk percentage was 12%. Controlling for asthma and atopy status, varicella vaccination was associated with reduced risk of HZ (aOR, 0.44; 95% CI, 0.21-0.92; P = .028). CONCLUSION: Asthma may be an unrecognized risk factor for reactivation of a non-airway-related latent infection such as HZ in children.

Hypereosinophilia: more than meets the eye.

INTRODUCTION: Eosinophilia has myriad causes and is occaisonally seen in association with malignancies. Acute myeloid leukemia presenting with eosinophilia has rarely been reported in children. CASE: Authors herein present a case of a 5-year-old boy who presented with marked peripheral eosinophilia with symptoms of organ infiltration. Extensive work-up was needed before the diagnosis was established in this patient. DISCUSSION: Through this case report, we want to emphasize that peripheral eosinophilia could be a dilemma challenging clinical skills and often needing vigorous perusal for the diagnosis.

Spice route movement: forum for young and future family physicians / primary care physicians of South Asia.

The past 6 years have seen the worldwide emergence of movements lead by New and Future Family/General Practitioners. The main aim of these movements is the promotion of excellence in the field of family medicine/general practice to respond the challenges pertaining to Global Health. This article will discuss some of the work being done worldwide, and in particularly in South Asia, in the context of The Spice Route movement. At the end of the article, details of the next steps to be taken and of ways in which interested parties can get involved are given.

Approach to polyarthritis.

A child with polyarthritis is always a diagnostic challenge for the treating physician. By definition, polyarthritis, taken in context as a subgroup of juvenile idiopathic arthritis, is defined as inflammation of more than 4 joints on physical examination. Though the exact incidence and prevalence of polyarthritis in childhood is not known, it is not uncommon in pediatric practice. Polyarthritis can be a clinical manifestation of diverse disease processes and the differential diagnosis is understandably very broad. It can be caused directly by an infectious agent or indirectly by immune mechanisms, may be a component of a systemic disease process or may be idiopathic. The presentation can be acute or chronic. It can represent a benign self limiting illness requiring no specific treatment or may be a severely disabling condition with significant morbidity and, in some cases, even mortality. While in some situations it may be possible to arrive at a provisional clinical diagnosis right at the outset, in others the diagnosis gradually evolves over a period of time. As in most other arthritides, the most important aspects of the diagnosis are a thorough history and a detailed clinical examination. Relevant laboratory investigations can help in facilitating the diagnosis but can often also mislead the treating physician. Hereby we present a clinical approach to a child with polyarthritis.