Upton Allen

Updated International Consensus Guidelines on the Management of Cytomegalovirus in Solid-Organ Transplantation

Cytomegalovirus (CMV) remains one of the most common infections after solid organ transplantation, resulting in significant morbidity, graft loss, and occasional mortality. Management of CMV varies considerably among transplant centers. A panel of experts on CMV and solid organ transplant was convened by The Infectious Diseases Section of The Transplantation Society to develop evidence and expert opinion-based consensus guidelines on CMV management including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues.

Canadian Society of Transplantation Consensus Workshop on Cytomegalovirus Management in Solid Organ Transplantation Final Report

The Canadian Society of Transplantation sponsored a Cytomegalovirus (CMV) Consensus Working Group that met on March 19, 2003. The objectives of this group were to determine the current burden of CMV‐associated disease in the setting of solid organ transplantation in Canada, make recommendations regarding optimal strategies for the diagnosis, treatment and prevention of CMV infection and disease, highlight gaps in knowledge and outline priorities for research and other initiatives that might further reduce the burden of CMV‐associated effects in this setting. This report summarizes the recommendations of the working group including ratings of the strength of evidence supporting the recommendations.

Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study

BACKGROUND There are few data on the epidemiology and outcomes of influenza infection in recipients of solid-organ transplants. We aimed to establish the outcomes of pandemic influenza A H1N1 and factors leading to severe disease in a cohort of patients who had received transplants. METHODS We did a multicentre cohort study of adults and children who had received organ transplants with microbiological confirmation of influenza A infection from April to December, 2009. Centres were identified through the American Society of Transplantation Influenza Collaborative Study Group. Demographics, clinical presentation, treatment, and outcomes were assessed. Severity of disease was measured by admission to hospital and intensive care units (ICUs). The data were analysed with descriptive statistics. Proportions were compared by use of chi(2) tests. We used univariate analysis to identify factors leading to pneumonia, admission to hospital, and admission to an ICU. Multivariate analysis was done by use of a stepwise logistic regression model. We analysed deaths with Kaplan-Meier survival analysis. FINDINGS We assessed 237 cases of medically attended influenza A H1N1 reported from 26 transplant centres during the study period. Transplant types included kidney, liver, heart, lung, and others. Both adults (154 patients; median age 47 years) and children (83; 9 years) were assessed. Median time from transplant was 3.6 years. 167 (71%) of 237 patients were admitted to hospital. Data on complications were available for 230 patients; 73 (32%) had pneumonia, 37 (16%) were admitted to ICUs, and ten (4%) died. Antiviral treatment was used in 223 (94%) patients (primarily oseltamivir monotherapy). Seven (8%) patients given antiviral drugs within 48 h of symptom onset were admitted to an ICU compared with 28 (22.4%) given antivirals later (p=0.007). Children who received transplants were less likely to present with pneumonia than adults, but rates of admission to hospital and ICU were similar. INTERPRETATION Influenza A H1N1 caused substantial morbidity in recipients of solid-organ transplants during the 2009-10 pandemic. Starting antiviral therapy early is associated with clinical benefit as measured by need for ICU admission and mechanical ventilation. FUNDING None.

Risk factors and outcomes among children admitted to hospital with pandemic H1N1 influenza

Background: Limited data are available on disease characteristics and outcomes of children with 2009 pandemic influenza A(H1N1) virus infection (pandemic H1N1 influenza) who have required hospital admission. Methods: We reviewed the charts of 58 children with pandemic H1N1 influenza admitted to a large pediatric hospital in Ontario, Canada, between May 8 and July 22, 2009. We compared risk factors, severity indicators and outcomes of these children with those of 200 children admitted with seasonal influenza A during the previous 5 years (2004/05 to 2008/09). Results: Children with pandemic H1N1 influenza were significantly older than those with seasonal influenza (median age 6.4 years v. 3.3 years). Forty-six (79%) of the children with pandemic H1N1 influenza had underlying medical conditions; of the other 12 who were previously healthy, 42% were under 2 years of age. Children admitted with pandemic H1N1 influenza were significantly more likely to have asthma than those with seasonal influenza (22% v. 6%). Two children had poorly controlled asthma, and 6 used inhaled medications only intermittently. The median length of stay in hospital was 4 days in both groups of children. Similar proportions of children required admission to the intensive care unit (21% of those with pandemic H1N1 influenza and 14% of those with seasonal influenza) and mechanical ventilation (12% and 10% respectively). None of the children admitted with pandemic H1N1 influenza died, as compared with 1 (0.4%) of those admitted with seasonal influenza. Interpretation: Pandemic H1N1 influenza did not appear to cause more severe disease than seasonal influenza A. Asthma appears to be a significant risk factor for severe disease, with no clear relation to severity of asthma. This finding should influence strategies for vaccination and pre-emptive antiviral therapy.

Dexamethasone in salbutamol-treated inpatients with acute bronchiolitis: a randomized, controlled trial.

OBJECTIVE To determine the clinical benefit of oral dexamethasone in children admitted to the hospital with bronchiolitis treated with nebulized salbutamol. METHODS Randomized, double-blind, placebo-controlled trial in the inpatient wards of a pediatric tertiary care hospital. The participants, children aged 6 weeks to 15 months, admitted with first-time wheezing, were eligible if their oxygen saturation was less than 95% on admission to the hospital and their Respiratory Distress Assessment Instrument (RDAI) score was greater than 6. Patients were excluded if they had any one of the following: an underlying disease that might affect cardiopulmonary status, asthma, recent treatment with steroids (within 2 weeks), or any history of adverse reaction to steroids. Patients were randomly assigned to receive either orally administered dexamethasone with 0.5 mg/kg as the first dose and 0.3 mg/kg for the next 2 mornings, or an equal volume of an orally administered placebo with an identical appearance. All patients received nebulized salbutamol at 0.15 mg/kg every 4 hours for the first 24 hours. The primary outcome measure was the change from baseline in the RDAI score at 24 hours. Secondary outcome measures were oxygen saturation, respiratory rate, RDAI measurement twice daily for the first 4 days, and the length of hospitalization. RESULTS At 24 hours the mean change (SD) from baseline in the RDAI score was 1.6 (2.3) in the placebo group (n = 28) and 1.4 (2.0) in the dexamethasone group (n = 33; p = 0.74). There were no significant differences between the two groups in change in oxygen saturation, respiratory rate, and RDAI score at any assessment period. The median length of stay (95% confidence interval) for the placebo group was 48 (42, 54) hours compared with 57 (38, 76) hours in the dexamethasone group (p = 0.19). CONCLUSIONS Oral dexamethasone therapy does not affect the clinical course of children hospitalized with bronchiolitis and therefore cannot be recommended in this clinical situation.

Epstein-barr virus and posttransplant lymphoproliferative disorder in solid organ transplant recipients.

Posttransplant lymphoproliferative disorder (PTLD) is recognized as potentially one of the most devastating complications of organ transplantation. Epstein-Barr virus (EBV) is associated with the majority of PTLD cases. The entity referred to as EBV-associated PTLD encompasses a wide spectrum of clinical conditions characterized by lymphoproliferation after transplantation. These syndromes range from uncomplicated infectious mononucleosis to true malignancies (1–3). Disease may be nodal or extranodal, localized, often in the allograft, or widely disseminated. Patients may be symptomatic or asymptomatic. PTLD may resemble a self-limited infection or be indistinguishable from non-Hodgkin’s lymphoma. Lesions may be localized and progress slowly or the patient may present with a fulminant multisystem sepsis-like syndrome.

Guidance on novel influenza A/H1N1 in solid organ transplant recipients.

Novel influenza A/H1N1 virus has caused significant illness worldwide. In response to this global crisis, the American Society of Transplantation (AST) Infectious Diseases Community of Practice and the Transplant Infectious Diseases section of The Transplantation Society (TTS) developed a guidance document for novel H1N1. In this paper, we discuss current guidance for H1N1 as it relates to solid organ transplantation. We include discussion around clinical presentation, diagnosis, therapy and prevention specifically addressing areas such as chemoprophylaxis, immunization and donor‐derived infection. Although this document addresses conditions specific to novel H1N1, many principles could be applied to future pandemics. As new information emerges about novel H1N1, updates will be made to the electronic version of the document posted on the websites of the AST and TTS.

LYMPHOPROLIFERATIVE DISORDERS AFTER ORGAN TRANSPLANTATION IN CHILDREN

BACKGROUND After organ transplant, patients are at risk of posttransplant lymphoproliferative disorders (PTLD). The purpose of this study was to analyze 26 pediatric cases of PTLD observed at our institution between 1988 and 1996, and to evaluate the validity of the Society for Hematopathology Workshop (SHPW) 1997 classification in our patient population. METHODS Charts were reviewed for analysis of incidence, clinical course, and outcome. Tissue samples were classified by a pathologist according to SHPW recommendations. RESULTS By morphology, 20 were monomorphic, 5 polymorphic, and 1 hyperplastic. Assessment of lineage by morphology, molecular studies, and immunophenotyping did not correlate in six cases. By immunophenotyping, 12 were B cell, 4 T cell, 8 mixed B/T cells, and 2 undetermined. The 20 patients evaluable for treatment efficacy were treated with various therapeutic combinations, including immunosuppressive drug reduction, acyclovir/ganciclovir, interferon-alpha, immunoglobulins, surgery, and local irradiation. No patient received systemic chemotherapy. Thirteen patients achieved complete remission and 3, partial; 1 died 5 days after starting therapy, and 3 of progressive disease. Adverse prognostic factors included low platelet or neutrophil counts; stage III-IV and SHPW morphology were marginally significant. CONCLUSIONS The majority of patients eligible for treatment can be cured with immunosuppressive drug reduction and antiviral drugs, along with surgery and irradiation when indicated. Systemic chemotherapy or innovative approaches may have a role in unresponsive cases. Morphologic SHPW grouping is feasible and seems to have clinical relevance. However, correlation with clonality and immunophenotyping is not always possible, necessitating modifications including segregation of descriptive morphology from clonality and cell origin.

Influenza Vaccination in the Organ Transplant Recipient: Review and Summary Recommendations

Influenza virus causes a spectrum of illness in transplant recipients with a high rate of lower respiratory disease. Seasonal influenza vaccination is an important public health measure recommended for transplant recipients and their close contacts. Vaccine has been shown to be safe and generally well tolerated in both adult and pediatric transplant recipients. However, responses to vaccine are variable and are dependent on various factors including time from transplantation and specific immunosuppressive medication. Seasonal influenza vaccine has demonstrated safety and no conclusive evidence exists for a link between vaccination and allograft dysfunction. Annually updated trivalent inactivated influenza vaccines have been available and routinely used for several decades, although newer influenza vaccination formulations including high‐dose vaccine, adjuvanted vaccine, quadrivalent inactivated vaccine and vaccine by intradermal delivery system are now available or will be available in the near future. Safety and immunogenicity data of these new formulations in transplant recipients requires investigation. In this document, we review the current state of knowledge on influenza vaccines in transplant recipients and make recommendations on the use of vaccine in both adult and pediatric organ transplant recipients.

Evaluation of the Utility of Radiography in Acute Bronchiolitis

Objectives To determine the proportion of radiographs inconsistent with bronchiolitis in children with typical presentation of bronchiolitis and to compare rates of intended antibiotic therapy before radiography versus those given antibiotics after radiography. Study design We conducted a prospective cohort study in a pediatric emergency department of 265 infants aged 2 to 23 months with radiographs showing either airway disease only (simple bronchiolitis), airway and airspace disease (complex bronchiolitis), and inconsistent diagnoses (eg, lobar consolidation). Results The rate of inconsistent radiographs was 2 of 265 cases (0.75%; 95% CI 0-1.8). A total of 246 children (92.8%) had simple radiographs, and 17 radiographs (6.9%) were complex. To identify 1 inconsistent and 1 complex radiograph requires imaging 133 and 15 children, respectively. Of 148 infants with oxygen saturation >92% and a respiratory disease assessment score <10 of 17 points, 143 (96.6%) had a simple radiograph, compared with 102 of 117 infants (87.2%) with higher scores or lower saturation (odds ratio, 3.9; 95% CI, 1.3-14.3). Seven infants (2.6%) were identified for antibiotics pre-radiography; 39 infants (14.7%) received antibiotics post-radiography (95% CI, 8-16). Conclusions Infants with typical bronchiolitis do not need imaging because it is almost always consistent with bronchiolitis. Risk of airspace disease appears particularly low in children with saturation higher than 92% and mild to moderate distress.