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

Abstract

Summary 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 χ2 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.

Clinical features and outcome of 2009-influenza A (H1N1) after allogeneic hematopoietic SCT

“…H1N1-related LRTI developed in 50%, of patients, which is in the range of 31-68% of almost all other series. [14][15][16]18,19,26,27 The 30% mechanical ventilation and 20% case fatality rates observed in our study correspond to those found in other small series, 16,18,19,[27][28][29] but are higher than the frequencies reported in larger series (4.0-13.5% and 3.0-7.3%, respectively). 14,22,26 Although this may reflect a reporting bias if patients with more severe illness were more likely to come to medical attention, we believe that allo-HSCT recipients are at higher risk for severe complications, notably in case of development of H1N1 oseltamivir-resistant strains 15,19 or concomitant respiratory pathogens.…”

“…Notably in this study, 31% of patients had ill household contacts. 26 Taken together, these observations should alert physicians involved in the care of HSCT patients about the high risk of viral transmission through close contact with children, underlining the importance of education and vaccination of patients and their family households. Close contact with symptomatic children should be avoided whenever possible during periods of RVI epidemics.…”

“…14,22,26 Although this may reflect a reporting bias if patients with more severe illness were more likely to come to medical attention, we believe that allo-HSCT recipients are at higher risk for severe complications, notably in case of development of H1N1 oseltamivir-resistant strains 15,19 or concomitant respiratory pathogens. 16,19,26,27,[30][31][32] The average duration of H1N1 viral shedding in the general population was B6 days. [9][10][11] Redelman-Sidi et al 17 failed to demonstrate a significant prolonged viral shedding in HSCT patients.…”

“…1 Indeed, approximately one child in every three was infected with H1N1 in England, 24 whereas in the United States, the rate of secondary outbreaks in households was 13% with children at increased risk for infection by a factor of 4. 25 Similarly, Kumar et al 26 reported that pediatric solid organ transplant recipients were substantially more likely to have fever, rhinorrhoea, sore throat and headache at presentation than were adult patients. Notably in this study, 31% of patients had ill household contacts.…”

“…Interestingly, LRTI, prolonged viral shedding, hospitalization, longer antiviral treatment, ventilator requirement and H1N1 resistance were documented only in SID patients. Lymphopenia, which has been previously reported as a risk factor for LRTI, both for community-acquired RVI [1][2][3][4]33 and for H1N1 influenza 9,[14][15][16][17][18]26 was observed in six patients at the time of diagnosis. Chronic GvHD and its corollary of long-term immunosuppression has also been associated with the risk of developing RVI and LRTI.…”