Differences in clinical outcomes after 2009 influenza A/H1N1 and seasonal influenza among hematopoietic cell transplant recipients

It is not known whether pandemic 2009 influenza A/H1N1 (2009 H1N1) leads to more serious disease than seasonal influenza in hematopoietic cell transplant (HCT) recipients. In a retrospective study in HCT recipients with virologically proven influenza virus infection, a total of 161 HCT recipients (18 2009 H1N1, 103 seasonal influenza A, and 40 seasonal influenza B) were analyzed. In multivariable analyses, more patients with 2009 H1N1 had lower respiratory tract disease (LRD), hypoxemia, and prolonged viral shedding compared with seasonal influenza A. Seasonal influenza A and B outcomes were similar. There was no difference in overall and influenza-associated mortality among influenza virus types. Both early and delayed administration of antiviral therapy was shown to be beneficial in terms of decreased rates of development of LRD, although earlier intervention appeared to be more effective. Profound lymphopenia and lack of early antiviral therapy were associated significantly with LRD, hypoxemia, and death. High-dose corticosteroid treatment (≥ 1 mg/kg) given at the time of influenza diagnosis was associated with a reduced risk for mechanical ventilation. Thus, our data suggest that infection with 2009 influenza A/H1N1 resulted in more severe respiratory disease in HCT recipients compared with seasonal influenza.     

Influenza A/H1N1 2009 pneumonia in kidney transplant recipients: characteristics and outcomes following high‐dose oseltamivir exposure

S.P. Watcharananan, T. Suwatanapongched, P. Wacharawanichkul, W. Chantratitaya, V. Mavichak, S.B. Mossad. Influenza A/H1N1 2009 pneumonia in kidney transplant recipients: characteristics and outcomes following high‐dose oseltamivir exposure.
Transpl Infect Dis 2010: 12: 127–131. All rights reserved Abstract: We report 2 cases of severe pneumonia due to the novel pandemic influenza A/H1N1 2009 in kidney transplant recipients. Our patients initially experienced influenza‐like illness that rapidly progressed to severe pneumonia within 48 h. The patients became hypoxic and required non‐invasive ventilation. The novel influenza A/H1N1 2009 was identified from their nasal swabs. These cases were treated successfully with a relatively high dose of oseltamivir, adjusted for their renal function. Clinical improvement was documented only after a week of antiviral therapy. Despite early antiviral treatment, we showed that morbidity following novel pandemic influenza A/H1N1 2009 infection is high among kidney transplant recipients.     

Outcome of pandemic H1N1 infections in hematopoietic stem cell transplant recipients

During 2009, a new strain of A/H1N1 influenza appeared and became pandemic. A prospective study was performed to collect data regarding risk factors and outcome of A/H1N1 in hematopoietic stem cell transplant recipients. Only verified pandemic A/H1N1 influenza strains were included: 286 patients were reported, 222 allogeneic and 64 autologous recipients. The median age was 38.3 years and the median time from transplant was 19.4 months. Oseltamivir was administered to 267 patients and 15 patients received zanamivir. One hundred and twenty-five patients (43.7%) were hospitalized. Ninety-three patients (32.5%) developed lower respiratory tract disease. In multivariate analysis, risk factors were age (OR 1.025; 1.01-1.04; P=0.002) and lymphopenia (OR 2.49; 1.33-4.67; P<0.001). Thirty-three patients (11.5%) required mechanical ventilation. Eighteen patients (6.3%) died from A/H1N1 infection or its complications. Neutropenia (P=0.03) and patient age (P=0.04) were significant risk factors for death. The 2009 A/H1N1 influenza pandemic caused severe complications in stem cell transplant recipients.     

Novel H1N1 influenza A virus infection in a patient with acute rejection after liver transplantation

BACKGROUND:The 2009 H1N1 influenza A virus was first identified in April 2009 and rapidly evolved into a pandemic. Recipients of solid-organ transplants have a higher risk for severe infection because of immunosuppression.There are limited reports of 2009 H1N1 influenza in liver transplant recipients,especially in China. METHODS:We present a case of a 48-year-old male liver transplant recipient with 2009 H1N1 influenza A virus.He received therapy for acute rejection after transplantation and was confirmed with H1N1 virus infection. RESULTS:The patient was started on oseltamivir(75 mg, orally twice daily)and had a benign hospital course,with defervescence and resolution of symptoms within 72 hours. The follow-up chest radiograph after discharge was normal. CONCLUSIONS:The 2009 H1N1 influenza in this hospitalized transplant recipient was relatively mild,and prolonged viral shedding was not noted.Oseltamivir can be a valid measure in immunocompromised individuals.     

Pandemic (H1N1) 2009 influenza in Canadian pediatric cancer and hematopoietic stem cell transplant patients

Please cite this paper as: Tran et al. (2012) Pandemic (H1N1) 2009 influenza in Canadian pediatric cancer and hematopoietic stem cell transplant patients. Influenza and Other Respiratory Viruses 6(601), e105–e113. Background The impact of pandemic H1N1 influenza (pH1N1) virus in pediatric cancer is uncertain. The objectives of this study were to characterize the clinical course of pH1N1 and identify factors associated with severe outcomes. Methods We conducted a Canadian multicenter retrospective review of children with cancer and stem cell transplant (SCT) recipients who were diagnosed with laboratory‐confirmed pH1N1 infection between May 1, 2009 and January 31, 2010. Results We identified 100 (19 in wave 1 and 81 in wave 2) cases of pH1N1 infection. Median age was 8·7 years. 71% had a hematologic malignancy, and 20% received SCT. Median duration of fever and illness was 2 and 12·5 days, respectively. 51 (51·5%) were hospitalized for a median of 5 days, with no deaths and only 1 requiring admission to the intensive care unit. Radiologically confirmed pneumonia was diagnosed in 10 (10%). Interruption of chemotherapy or conditioning occurred in 43 patients. In multivariable analyses, age <5 years (relative to ≥10 years) and neutropenia were associated with hospitalization while neutropenia was associated with pneumonia. Despite oseltamivir use in 89%, viral shedding was prolonged (median, 46 days) and often persisted after symptom resolution. However, an extended treatment course (>5 days) correlated with shortened duration of viral shedding (P = 0·041). Conclusions pH1N1 infection in pediatric cancer and SCT patients infrequently caused complications but commonly interrupted cancer treatment. Persistent shedding of virus after illness resolution was common. Further research is needed to verify this finding as it could have implications for treatment guidelines and infection control practices.     

Outbreak of pandemic 2009 influenza A/H1N1 infection in the hematology ward: fatal clinical outcome of hematopoietic stem cell transplant recipients and emergence of the H275Y neuraminidase mutation

We report an outbreak of pandemic 2009 influenza A/H1N1 virus (2009 H1N1) infection that occurred in the hematology ward of our institution during the 2010-2011 influenza season. A total of seven hospitalized patients with hematologic tumors, including five recipients of hematopoietic stem cell transplantation (HSCT), successively developed rapid influenza detection test (RIDT)-positive influenza A; four patients had laboratory-confirmed 2009 H1N1 infection. Three HSCT recipients required mechanical ventilation support and two were admitted to the intensive care unit; they died of progressive respiratory failure despite receiving available anti-viral drugs. We implemented outbreak-control measures including transferal of RIDT-positive patients to a single-patient room and chemoprophylaxis with oseltamivir. We note that the H275Y neuraminidase mutation was detected in respiratory specimens from three patients, who were administered therapeutic or prophylactic dosages of oseltamivir. The present report demonstrates that the nosocomial 2009 H1N1 outbreak in the hematology ward led to fatal clinical outcomes and the emergence of a resistant virus at a markedly high rate.     

Pandemic influenza A/H1N1 and organ donation

R. Lattes, N. Jacob, J. de la Fuente, G. Fragale, P. Massari. Pandemic influenza A/H1N1 and organ donation.
Transpl Infect Dis 2010: 12: 169–172. All rights reserved Abstract: One of the concerns regarding the pandemic of novel influenza A/H1N1 virus is its potential to hamper transplant programs if the decision is made that organs from donors with influenza A/H1N1 should not be used. Evidence of transmissibility through organ transplantation is speculative at best. We report the outcome of 2 kidney transplant recipients who received kidneys from the same deceased donor, in whom the diagnosis of infection by the novel virus became available only after engraftment. The donor also had received a complete course of antiviral treatment before donation. The recipients were transplanted at 2 different facilities and were managed differently. Neither recipient developed flu syndrome, and both had an uneventful outcome. It is possible to speculate that kidneys from donors who have had confirmed influenza A/H1N1 and who have received antiviral treatment can be safely used in transplantation.     

H1N1 (2009) influenza A infection in transplant recipient patients: a comparative study versus non-transplanted patients

Objective

To compare H1N1 (2009) influenza A infection characteristics between transplant recipient patients and non-transplanted patients. To assess the evolution of transplanted patients up to 6 months following infection.

Methods

Patients diagnosed with confirmed influenza A infection from three Parisian transplant centers between September 1st, 2009 and February 15th, 2010. Clinical symptoms, biological, and radiological findings, and management were analysed and retrospectively compared between transplanted (T) and non-transplanted patients (NT). The evolution was assessed by a follow-up questionnaire, CT results 1 to 3 months after influenza infection and FEV1 variation.

Results

Seventy patients were included. Thirteen patients had an allograft (lung: eight, kidney: four, stem cells: one): (1) hospitalization: 100% (13 out of 13) in group T, 54% (31 out of 57) in group NT (P = 0.0013); (2) pneumonia: 62% (eight out of 13) in group T, 26% (eight out of 57) in group NT (P = 0.004); (3) mortality rate among hospitalized patients: 7.7% (one out of 13) in the group T, 9.7% (three out of 57) in group NT (P = NS); (4) chest CT scan abnormalities remained in four lung transplanted patients; (5) a minimum 10% decrease in FEV1 was detected in four lung transplant recipients.

Conclusion

Our results suggest that H1N1(2009) influenza A infection in transplant recipient patients compared to non-transplanted patients: (1) more often leads to hospitalization; (2) is more frequently associated with pneumonia; (3) is responsible for a persistent graft functional impairment in lung transplant recipients; (4) has a low mortality rate similar to admitted non-transplanted patients.     

Efficient control of pandemic 2009 H1N1 virus infection with intravenous zanamivir despite the lack of immune function

A teenager who acquired 2009 H1N1 influenza A lower respiratory tract infection during total bone marrow and lymphoid aplasia, in the setting of human leukocyte antigen‐haploidentical hematopoietic stem cell transplantation, was successfully treated with intravenous zanamivir. This case demonstrates efficient control of pandemic influenza infection by intravenous zanamivir in the absence of any functional immune system, thus suggesting profound antiviral activity.     

Six adult cases of respiratory complications caused by pandemic 2009 influenza A (H1N1) compared to seasonal influenza

The first case in Japan of 2009 pandemic influenza A (H1N1) was reported in May, with pediatric hospitalization exceeding that of adults. We evaluated six adults hospitalized for 2009 H1N1 respiratory complications and compared the pandemic to seasonal influenza. Hospitalization was due to aggravated asthma in four of the six, two of whom had simultaneous pneumonia probably virus-caused, and two cases of bacterial pneumonia. Among the three seasons examined, the number of adults increased slightly but the hospitalization rate was low in 2009-2010. Respiratory complications such as viral pneumonia were not seen outside of 2009-2010. Attention should therefore be paid to respiratory complications in adults with pandemic 2009 influenza A (H1N1) virus.     

Clinical, laboratory and radiologic characteristics of 2009 pandemic influenza A/H1N1 pneumonia: primary influenza pneumonia versus concomitant/secondary bacterial pneumonia

Please cite this paper as: Song et al. (2011). Clinical, laboratory and radiologic characteristics of 2009 pandemic influenza A/H1N1 pneumonia: primary influenza pneumonia versus concomitant/secondary bacterial pneumonia. Influenza and Other Respiratory Viruses 5(6), e535–e543. Background Although influenza virus usually involves the upper respiratory tract, pneumonia was seen more frequently with the 2009 pandemic influenza A/H1N1 than with seasonal influenza. Methods From September 1, 2009, to January 31, 2010, a specialized clinic for patients (aged ≥15 years) with ILI was operated in Korea University Guro Hospital. RT‐PCR assay was performed to diagnose 2009 pandemic influenza A/H1N1. A retrospective case–case–control study was performed to determine the predictive factors for influenza pneumonia and to discriminate concomitant/secondary bacterial pneumonia from primary influenza pneumonia during the 2009–2010 pandemic. Results During the study period, the proportions of fatal cases and pneumonia development were 0·12% and 1·59%, respectively. Patients with pneumonic influenza were less likely to have nasal symptoms and extra‐pulmonary symptoms (myalgia, headache, and diarrhea) compared to patients with non‐pneumonic influenza. Crackle was audible in just about half of the patients with pneumonic influenza (38·5% of patients with primary influenza pneumonia and 53·3% of patients with concomitant/secondary bacterial pneumonia). Procalcitonin, C‐reactive protein (CRP), and lactate dehydrogenase were markedly increased in patients with influenza pneumonia. Furthermore, procalcitonin (cutoff value 0·35 ng/ml, sensitivity 81·8%, and specificity 66·7%) and CRP (cutoff value 86·5 mg/IU, sensitivity 81·8%, and specificity 59·3%) were discriminative between patients with concomitant/secondary bacterial pneumonia and patients with primary influenza pneumonia. Conclusions Considering the subtle manifestations of 2009 pandemic influenza A/H1N1 pneumonia in the early stage, high clinical suspicion is required to detect this condition. Both procalcitonin and CRP would be helpful to differentiate primary influenza pneumonia from concomitant/secondary bacterial pneumonia.     

Prior infection with classical swine H1N1 influenza viruses is associated with protective immunity to the 2009 pandemic H1N1 virus

Please cite this paper as: Kash et al. (2010) Prior infection with classical swine H1N1 influenza viruses is associated with protective immunity to the 2009 pandemic H1N1 virus. Influenza and Other Respiratory Viruses 4(3), 121–127. Background  The 2009 H1N1 pandemic emerged even though seasonal H1N1 viruses have circulated for decades. Epidemio‐logical evidence suggested that the current seasonal vaccine did not offer significant protection from the novel pandemic, and that people over the age of 50 might were less susceptible to infection. Objectives  In a mouse challenge study with the 2009 pandemic H1N1 virus, we evaluated protective immune responses elicited by prior infection with human and swine influenza A viruses. Results  Mice infected with A/Mexico/4108/2009 (Mex09) showed significant weight loss and 40% mortality. Prior infection with a 1976 classical swine H1N1 virus resulted in complete protection from Mex09 challenge. Prior infection with either a 2009 or a 1940 seasonal H1N1 influenza virus provided partial protection and a >100‐fold reduction in viral lung titers at day 4 post‐infection. Conclusions  These findings indicate that in experimental animals recently induced immunity to 1918‐derived H1N1 seasonal influenza viruses, and to a 1976 swine influenza virus, afford a degree of protection against the 2009 pandemic virus. Implications of these findings are discussed in the context of accumulating data suggesting partial protection of older persons during the 2009 pandemic.     

Role of procalcitonin and C-reactive protein in differentiation of mixed bacterial infection from 2009 H1N1 viral pneumonia

Please cite this paper as: Ahn et al. (2011) Role of procalcitonin and C‐reactive protein in differentiation of mixed bacterial infection from 2009 H1N1 viral pneumonia. Influenza and Other Respiratory Viruses 5(6), 398–403. Background Mixed bacterial infection is an important contributor to morbidity and mortality during influenza pandemics. We evaluated procalcitonin (PCT) and C‐reactive protein (CRP) in differentiating pneumonia caused by mixed bacterial and 2009 H1N1 influenza infection from 2009 H1N1 influenza infection alone. Methods Data were collected retrospectively over a 7‐month period during the 2009 H1N1 influenza pandemic. Patients visiting emergency department and diagnosed as community‐acquired pneumonia caused by 2009 H1N1 infection were included (n = 60). Results Mixed bacterial and viral infection pneumonia (n = 16) had significantly higher PCT and CRP levels than pneumonia caused by 2009 H1N1 influenza alone (n = 44, P = 0·019, 0·022 respectively). The sensitivity and specificity for detection of mixed bacterial infection pneumonia was 56% and 84% for PCT > 1·5 ng/ml, and 69% and 63% for CRP > 10 mg/dl. Using PCT and CRP in combination, the sensitivity and specificity were 50% and 93%, respectively. Conclusion Procalcitonin and CRP alone and their combination had a moderate ability to detect pneumonia of mixed bacterial infection during the 2009 H1N1 pandemic. Considering high specificity, combination of low CRP and PCT result may suggest that pneumonia is unlikely to be caused by mixed bacterial infection.     

Comparison of the patients with pandemic (H1N1) influenza A virus pneumonia and community-acquired pneumonia

Prognosis of pandemic influenza A (H1N1) virus pneumonia is worse than community-acquired pneumonia (CAP), therefore it is important to know distinctive clinical features of both pneumonias. The aims of this study were to compare clinical features and prognosis of patients with pandemic influenza A (H1N1) pneumonia and CAP due to other agents. Demographic features, symptoms and findings of 20 pandemic influenza A (H1N1) pneumonia and 18 CAP patients hospitalized between October 1st and December 30th, 2009 were evaluated. One patient (5.0%) with pandemic Influenza A (H1N1) pneumonia and 55.6% of CAP patients were over 65 years (p= 0.001). Symptoms of fever, dyspnea, fatigue, muscle and joint pain, nausea, vomiting and headache were more frequent (p< 0.05), platelet count (p= 0.024) and PaO(2)/FiO(2) ratio (p= 0.006) were lower, number of thrombocytopenic patients (p= 0.024) and LDH levels (p= 0.016) were higher, duration of hospitalization was longer (p= 0.038) in patients with pandemic influenza A (H1N1) pneumonia. There was no difference in terms of radiological findings between two groups. None of the CAP patients were followed-up in the intensive care, whereas five pandemic influenza A (H1N1) pneumonia patients (25.0%) required intensive care and three of them died despite invasive mechanical ventilation. In conclusion, in the presence of fever, dyspnea with non-pulmonary symptoms and accompanying radiological alveolar opacities should be considered as pandemic influenza A (H1N1) pneumonia should be suspected in patients admitted with findings of pneumonia during influenza season. Admission to the intensive care unit and mechanical ventilation should be considered in patients with dyspnea and diffuse radiological findings.     

Antiviral resistance during the 2009 influenza A H1N1 pandemic: public health, laboratory, and clinical perspectives

Influenza A H1N1 2009 virus caused the first pandemic in an era when neuraminidase inhibitor antiviral drugs were available in many countries. The experiences of detecting and responding to resistance during the pandemic provided important lessons for public health, laboratory testing, and clinical management. We propose recommendations for antiviral susceptibility testing, reporting results, and management of patients infected with 2009 pandemic influenza A H1N1. Sustained global monitoring for antiviral resistance among circulating influenza viruses is crucial to inform public health and clinical recommendations for antiviral use, especially since community spread of oseltamivir-resistant A H1N1 2009 virus remains a concern. Further studies are needed to better understand influenza management in specific patient groups, such as severely immunocompromised hosts, including optimisation of antiviral treatment, rapid sample testing, and timely reporting of susceptibility results.     

Bronchoscopic findings in a child with pandemic novel H1N1 influenza A and methicillin-resistant Staphylococcus aureus

The spectrum of disease with pandemic novel H1N1 influenza A (2009) virus ranges from non-febrile, mild upper respiratory tract infection to severe or fatal pneumonia. We report the bronchoscopic findings associated with a fatal case of H1N1 influenza A associated with co-infection with methicillin-resistant Staphylococcus aureus (MRSA) in a previously healthy child, which were more severe than those previously described as associated with seasonal influenza infection alone. The severity of the airway pathology seen on bronchoscopy in this patient may be due to a unique effect of the H1N1 influenza A virus or may be as a result of a destructive synergism between this virus and bacteria such as MRSA.     

Viral infections in immunocompromised patients: what's new with respiratory viruses?

PURPOSE OF REVIEW: The leading cause of death in solid organ and hematopoietic stem cell transplant recipients is infection. The respiratory viruses, particularly respiratory syncytial virus, influenza, parainfluenza, adenovirus, and picornaviruses, are increasingly recognized as significant pathogens in these populations. RECENT FINDINGS: Respiratory syncytial virus has again been found to be the most common of the respiratory viruses causing severe infections in transplant recipients. Advances in prevention, particularly with regard to infection control practices, and to lesser extent treatment have had a substantial impact on the frequency and outcomes of this infection. New studies have clarified the impact of influenza in the hematopoietic stem cell transplant recipients and have provided evidence to support the use of M2 and neuraminidase inhibitors for early treatment. The epidemiology of parainfluenza and adenovirus in transplant recipients has been clarified, although therapeutic modalities are still limited and understudied. New antiviral medications may bring improved outcomes of picornavirus infections in this population. Finally, a new virus, the human metapneumovirus, has recently been described and may be a significant respiratory pathogen in immunocompromised transplant recipients. SUMMARY: Studies published over the past year have documented a new respiratory pathogen. They have also resulted in improved understanding of the epidemiology of all of the respiratory virus pathogens, and have contributed to improve management of respiratory syncytial virus and influenza infection in hematopoietic stem cell transplant and solid organ transplant recipients.     

Prolonged lymphopenia in a patient with lymphoma and severe Pandemic influenza A H1N1 2009 virus infection

Please cite this paper as:Ñamendys‐Silva et al. (2011) Prolonged lymphopenia in a patient with lymphoma and severe Pandemic influenza A H1N1 2009 virus infection. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2010.00193.x. Objective To describe the clinical course of a confirmed influenza A Pandemic (H1N1) 2009 virus infection in a patient with lymphoblastic lymphoma on chemotherapy. Design Case report. Setting Instituto Nacional de Cancerología located in Mexico City, a national referral center for cancer patients. Patient and results A 15‐year‐old boy, with lymphoblastic lymphoma on chemotherapy. Oseltamivir 75 mg BID was started within 24 hour of first symptoms. The patient developed respiratory failure despite oseltamivir therapy; he presented a prolonged clinical course with severe lymphopenia and deteriorated every time oseltamivir was stopped while lymphopenia persisted. Oseltamivir was reassumed twice; in the second course, rimatadine was added. Genetic study of the virus showed 100% identity for AH1N1SW, and no H274Y mutation for oseltamivir resistance was found. Clinical recovery was apparent until he presented lymphocyte reconstitution after 35 days of disease while still on antiviral therapy. Conclusion This case exemplifies the need to sustain antiviral therapy while patient continues with severe lymphopenia. Lymphocyte count could be used as a surrogate marker to prolong antiviral therapy in patients with severe lymphopenia and clinically symptomatic Pandemic (H1N1) 2009 infection. This case also highlights the importance of treating patients based on clinical grounds and the variability of rRt‐PCR test for H1N1.