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.     

The clinical outcome and toxicity of high-dose chemotherapy and autologous stem cell transplantation in patients with myeloma or amyloid and severe renal impairment: a British Society of Blood and Marrow Transplantation study

The outcome of high-dose chemotherapy (HDT) was evaluated retrospectively in 27 patients with myeloma and four patients with AL amyloidosis with severe renal impairment. Twenty-three patients were receiving dialysis and the rest had a creatinine clearance of <20 ml/min. The median melphalan dose was 140 mg/m2 (range: 60-200 mg/m2), but 10 patients (37%) received 200 mg/m2. Myeloid and platelet engraftment were similar to that seen in patients without renal failure. Five of 27 patients died of transplant-related toxicity before the day 100. Twenty of 27 patients had a response (70%). The median time to disease progression was 32 months (range: 6-54 months) and the median time to best response was 6.5 months. Four of 17 evaluable patients (24%) became dialysis-independent at a median of 5 months post-HDT/stem cell transplantation. At a median follow-up of 70 months, 7/23 patients with myeloma were alive but three of these seven patients had progressive disease. Two of the four patients with amyloidosis have survived. HDT is feasible in these patients and results in 5-year survival in about one-third of patients.     

Cytokine response in pediatric patients with pandemic influenza H1N1 2009 virus infection and pneumonia: comparison with pediatric pneumonia without H1N1 2009 infection

Objectives

We investigated serum cytokine levels in pediatric patients with pandemic influenza H1N1 2009 virus (H1N1) infection‐pneumonia and in pediatric patients with pneumonia but without H1N1 infection, and examined correlations between cytokine levels and clinical/laboratory findings.

Methods

Fifty‐seven cases of infection by H1N1 were confirmed by RT‐PCR and enrolled. Of these 57 cases, 26 had a severe H1N1 infection (group 1), and 31 had a mild H1N1 infection (group 2). Sera from 18 cases with pneumonia without H1N1 infection (group 3) were used as controls. The serum levels of 10 cytokines were determined by multiplex assay.

Results

The serum levels of IFN‐α, IL‐6, and IP‐10 were significantly higher in H1N1 infected cases than in group 3, and levels of IL‐6 and IP‐10 were significantly higher in group 1 than in group 2. The level of IL‐10 was significantly higher in groups 1 and 3 than in group 2. However, levels of IFN‐γ and IL‐17 were not significantly different between the three groups. IL‐1β, IL‐4, and MIP‐1α were not detectable in most patients. IP‐10 and IL‐6 levels were found to show negative correlations with lymphocyte count and oxygen saturation.

Conclusions

We found higher levels of cytokines (IFN‐α, IL‐6, IP‐10) of innate immunity than those of acquired immunity in pediatric H1N1 infection. Of the cytokines found to be increased in cases with H1N1 infection, IP‐10 and IL‐6 were found to be correlated with disease severity (lymphopenia and hypoxia). IP‐10 and IL‐6 may be important markers in pediatric H1N1 infection. Pediatr Pulmonol. 2011; 46: 1233–1239. © 2011 Wiley Periodicals, Inc.

     

新型甲型H1N1流感重症患者肺部影像学变化及临床特点

目的 探讨新型甲型H1N1流感(简称甲型流感)危重病例肺部影像学的变化及其临床特点. 方法 山西省太原市第四人民医院2009年10月20日至11月22日收治的10例重症甲型流感确诊患者,男6例,女4例,年龄5～41岁,平均19.3岁.采用常规技术检测血常规、血气指标、肝肾功能及心肌酶学变化,并行胸部X线及CT检查;给予奥司他韦、吸氧、呼吸支持、抗感染及对症支持等综合治疗. 结果 患者均以发热、咳嗽、呼吸困难为主要症状,肺部病灶表现多种多样,表现为磨玻璃影及实变影、肺不张、液气胸及胸腔积液等征象,进展快,同时存在急性肺炎和急性间质性肺炎的影像学改变,10例中5例发展为急性肺损伤,3例发展为ARDS;奥司他韦、呼吸支持及抗感染治疗有效. 结论 甲型流感危重病例的影像学表现为急性肺炎和急性间质性肺炎改变,临床表现为病情重、进展快,可发展为ARDS.     

新型甲型H1N1流感重症患者肺部影像学变化及临床特点

目的 探讨新型甲型H1N1流感(简称甲型流感)危重病例肺部影像学的变化及其临床特点. 方法 山西省太原市第四人民医院2009年10月20日至11月22日收治的10例重症甲型流感确诊患者,男6例,女4例,年龄5～41岁,平均19.3岁.采用常规技术检测血常规、血气指标、肝肾功能及心肌酶学变化,并行胸部X线及CT检查;给予奥司他韦、吸氧、呼吸支持、抗感染及对症支持等综合治疗. 结果 患者均以发热、咳嗽、呼吸困难为主要症状,肺部病灶表现多种多样,表现为磨玻璃影及实变影、肺不张、液气胸及胸腔积液等征象,进展快,同时存在急性肺炎和急性间质性肺炎的影像学改变,10例中5例发展为急性肺损伤,3例发展为ARDS;奥司他韦、呼吸支持及抗感染治疗有效. 结论 甲型流感危重病例的影像学表现为急性肺炎和急性间质性肺炎改变,临床表现为病情重、进展快,可发展为ARDS.     

新型甲型H1N1流感重症患者肺部影像学变化及临床特点

目的 探讨新型甲型H1N1流感(简称甲型流感)危重病例肺部影像学的变化及其临床特点. 方法 山西省太原市第四人民医院2009年10月20日至11月22日收治的10例重症甲型流感确诊患者,男6例,女4例,年龄5～41岁,平均19.3岁.采用常规技术检测血常规、血气指标、肝肾功能及心肌酶学变化,并行胸部X线及CT检查;给予奥司他韦、吸氧、呼吸支持、抗感染及对症支持等综合治疗. 结果 患者均以发热、咳嗽、呼吸困难为主要症状,肺部病灶表现多种多样,表现为磨玻璃影及实变影、肺不张、液气胸及胸腔积液等征象,进展快,同时存在急性肺炎和急性间质性肺炎的影像学改变,10例中5例发展为急性肺损伤,3例发展为ARDS;奥司他韦、呼吸支持及抗感染治疗有效. 结论 甲型流感危重病例的影像学表现为急性肺炎和急性间质性肺炎改变,临床表现为病情重、进展快,可发展为ARDS.     

Isolation of Aspergillus in three 2009 H1N1 influenza patients

OBJECTIVES: To describe the association of Aspergillus with influenza. DESIGN/SETTING/SAMPLE: Three case reports of ICU patients with influenza complicated by the isolation of Aspergillus species are described and a review of the literature on the topic was performed. CONCLUSIONS: Severe influenza cases can be complicated by Aspergillus infection.     

Asthma and severity of the 2009 novel H1N1 influenza: a case-control study

Objective: Previous studies reported that the most common chronic condition found among hospitalized patients due to the novel 2009 H1N1 influenza was asthma. However, these studies did not include a concurrent control group. Thus, we investigated the association of asthma status and severity of H1N1 influenza in adults. Methods: The study was designed as a multi-site case-control study. Cases were patients who had positive PCR for H1N1 influenza and were admitted to the ICU or general ward with a diagnosis of H1N1 influenza from 1 January 2009 to 31 December 2009. Controls were patients who had positive PCR for H1N1 influenza, but were not admitted to hospitals. Results: There were 91 H1N1 cases admitted to either ICU (n?=?41) or general hospital ward (n?=?50), and 56 controls who met the matching criteria were available. Of the 91 cases, the mean age was 47.3 years, 59% were female, and 38% had comorbid conditions. Of the 91 cases, 12 (13%) had asthma. Stratified analysis by comorbid conditions showed that among those without any comorbid conditions, 8 of 56 cases (14%) and 2 of 49 controls (4%) had asthma, (OR: 3.92, 95% CI: 0.79–19.42, p?=?0.095) whereas, among the 39 subjects with one or more comorbid conditions, one of 7 controls (14%) had asthma and 4 of 35 (11%) cases had asthma (p?=?0.83). Conclusions: Asthma may be associated with severity of H1N1 influenza among those without any non-asthma comorbid conditions. However, the limited sample size did not allow this study to fully establish statistical significance. We still recommend asthmatics as a priority group for influenza vaccination and treatment.     

Course of pandemic influenza A(H1N1) 2009 virus infection in Dutch patients

The clinical dynamics of influenza A(H1N1) 2009 infections in 61 laboratory-confirmed Dutch cases were examined. An episode lasted a median of 7·5 days of which 2 days included fever. Respiratory symptoms resolved slowly, while systemic symptoms peaked early in the episode and disappeared quickly. Severity of each symptom was rated highest in the first few days. Furthermore, diarrhoea was negatively associated with viral load, but not with faecal excretion of influenza virus. Cases with comorbidities appeared to have higher viral loads than the cases without, suggesting a less effective immune response. These results complement information obtained through traditional surveillance.     

Systematic review of clinical and epidemiological features of the pandemic influenza A (H1N1) 2009

The aim of this systematic review was to summarise the clinical and epidemiological features of the pandemic influenza A (H1N1) 2009. We did a systematic search of published literature reporting clinical features of laboratory-confirmed pandemic influenza A (H1N1) 2009 from 1 April 2009 to 31 January 2010. Forty-four articles met our inclusion criteria for the review. The calculated weighted mean age of confirmed cases was 18·1 years, with the median ranging from 12 to 44 years. Cough (84·9%), fever (84·7%), headache (66·5%), runny nose (60·1%) and muscle pain (58·1%) were the most common symptoms of confirmed cases. One or more pre-existing chronic medical conditions were found in 18·4% of cases. Almost two-thirds (64%) of cases were aged between 10 and 29 years, 5·1% were aged over 50 years and only 1·1% were aged over 60 years. The confirmed case fatality ratio was 2·9% (95% CI 0·0-6·7%), an extracted average from 12 of 42 studies reporting fatal cases (937 fatal cases among 31,980 confirmed cases), which gives an overall estimated infected case fatality ratio of 0·02%. Early in the pandemic, disease occurred overwhelmingly in children and younger adults, with cough and fever as the most prevalent clinical symptoms of the confirmed cases. A high infection rate in children and young adults, with sparing of the elderly population, has implications for pandemic influenza management and control policies.     

Oseltamivir-resistant influenza A 2009 H1N1 virus in immunocompromised patients

Please cite this paper as: Couturier et al. (2010). Oseltamivir-resistant influenza A 2009 H1N1 virus in immunocompromised patients. Influenza and Other Respiratory Viruses 4(4), 199–204. Background First-line treatment of influenza A 2009 H1N1 relies on neuraminidase inhibitors such as oseltamivir. Resistance conferred by the H275Y neuraminidase gene mutation is concerning and likely to increase. Objectives To characterize oseltamivir resistance in a hospital-based patient population. Patients and Methods All available respiratory specimens positive for influenza A by direct fluorescent antibody, RT-PCR, or culture from patients at the University of Utah 5/09-12/09 were collected. Specimens were confirmed as 2009 H1N1 by the Utah Department of Health. RT-PCR and pyrosequencing were used to test for the H275Y mutation (CDC protocol). Pyro Mark Q24 AQ software (Qiagen, Valencia, CA, USA) was used to allow for quantitative H275Y mutation analysis. Medical records of patients with resistant virus were reviewed. Results We tested 191 influenza A virus-positive samples from 187 unique patients. Fifty (27%) patients were hospitalized. Four patient specimens (2·1%) were found to carry the H275Y mutation. Three patients were hospitalized, representing 6% of inpatient samples tested. Three patients had undergone hematopoietic stem cell transplant in the past year. Two patients died. Their influenza viruses were confirmed to be oseltamivir-resistant at an independent reference laboratory and through the Center for Disease Control and Prevention (CDC). One patient reported no history of prior oseltamivir exposure. Conclusions Widespread oseltamivir resistance among 2009 H1N1 remains a potential threat. Rapid techniques, such as pyrosequencing, which has the additional benefit of identifying mixed mutant populations of virus, may play a key role in identifying at-risk individuals and potentially unsuspected cases. Targeted surveillance of immunocompromised patients will be critical toward improving future influenza planning and therapy.     

Comparison of a live attenuated 2009 H1N1 vaccine with seasonal influenza vaccines against 2009 pandemic H1N1 virus infection in mice and ferrets

The role of seasonal influenza vaccination in pandemic influenza A H1N1 disease is important to address, because a large segment of the population is vaccinated annually. We administered 1 or 2 doses of pandemic H1N1 vaccine (CA/7 ca), a seasonal trivalent inactivated (s-TIV), or live attenuated influenza vaccine (s-LAIV) to mice and ferrets and subsequently challenged them with a pandemic H1N1 virus. In both species, CA/7 ca was immunogenic and conferred complete protection against challenge. s-TIV did not confer protection in either animal model, and s-LAIV did not confer any protection in ferrets. In mice, 2 doses of s-LAIV led to complete protection in the upper respiratory tract and partial protection in the lungs. Our data indicate that vaccination with the seasonal influenza vaccines did not confer complete protection in the lower respiratory tract in either animal model, whereas the CA/7 ca vaccine conferred complete protection in both animal models.     

The outcome of haemopoietic stem cell transplantation in the treatment of lymphoplasmacytic lymphoma in the UK: a British Society Bone Marrow Transplantation study

Lymphoplasmacytic lymphoma (LL) is incurable by standard therapy (median survival: 60 months). UK transplant registry data 1984-2003 identified 18 cases of histologically verified LL (median age: 50 years, range: 38-58 years). Nine patients received high dose chemotherapy [plus total body irradiation (TBI) in 1/9] and autologous peripheral blood stem cells (PBSC). Disease status at transplant was complete remission (2), partial remission (5), primary refractory (1) or relapse (1). Transplant related mortality (TRM) at 12 months was 0%. Median follow-up is 44 months with 4 year disease free survival 43% and overall survival 73%. Karnofsky performance status (KPS) is 80-100%. The nine allografted patients (median age: 49 years, range: 39-56 years) were conditioned with standard TBI (2), BEAM (2) or FLU-MEL (5) and received PBSC from HLA-matched sibling (8) or unrelated (1) donors. Disease status at transplant was partial remission (7) or primary refractory (2). TRM at 12 months was 44%. Complications included graft failure (2), grades I-II acute graft versus host disease (aGVHD) (2), grades III-IV aGVHD (3) and chronic GVHD (4). Median follow-up is 32 months with 4 year disease free survival 44% and overall survival 56%. KPS is 70-100%.