Last year’s pandemic H1N1 infection was especially dangerous for solid organ transplant recipients, although individuals who received early antiviral therapy experienced less morbidity and better outcomes compared with those who did not, according to a study reported online July 9 in the Lancet Infectious Diseases.
More than two-thirds of the solid organ transplant recipients infected with the influenza A strain who were included in a multicenter cohort investigation required hospital admission and 4% died from flu-related complications, wrote Dr. Deepali Kumar of the University of Alberta, Edmonton, Canada, and her colleagues.
Those individuals who received antiviral therapy within 48 hours of symptom onset were less likely to require hospitalization or ventilation support, they wrote (Lancet Infect. Dis. 2010 July 9 [doi:10.1016/S1473-3099(10)70133-X]).
The investigators reviewed medical charts from 26 transplant centers in the United States and Canada for patients who had microbiologically confirmed infection with influenza A(H1N1) from April to December 2009. Of the 237 cases assessed – including 154 adults, median age 47 years, and 83 children, median age 9 years – 87 were kidney transplants, 47 were liver transplants, 33 were lung transplants, 45 were heart transplants, 5 were intestinal transplants, and 20 involved other organs, they stated.
The median time of H1N1 symptom onset after transplantation was 3.6 years, and the most common presenting symptoms were cough, fever, myalgias, rhinorrhea, sore throat, and headache, the authors reported.
Imaging findings in 73 of the 230 patients for whom chest radiograph or CT data were available were consistent with pneumonia, and bacterial pathogens were identified from sputum or bronchoalveolar lavage fluid in 13 of the 237 patients. Other complications included concomitant cytomegalovirus viremia in 8 patients, 4 cases of otitis media, 2 cases of sinusitis, and 1 case of encephalitis.
Vaccination data were not available for the full cohort, the authors wrote, noting that, before symptom onset, “55 [40%] of 139 patients had received the 2009-2010 seasonal influenza vaccination and 20 [11%] of 177 patients had been immunized with pandemic H1N1 vaccine.”
Of the 237 patients, all but 14 received antiviral therapy, primarily oseltamivir. Antiviral therapy was initiated within 48 hours in 42% of the patients, between 48 and 96 hours in 29%, and after 96 hours in 29%, they wrote.
In all, 70% of the patients were hospitalized at a median of 2 days after symptom onset and 16% were admitted to the intensive care unit (ICU) at a median of 5 days after symptom onset. Of the 37 patients requiring ICU admission, 21 needed mechanical ventilation for a median of 12 days.
In a univariate analysis of factors associated with ICU admission, early antiviral treatment was associated with a lower likelihood of this outcome (8%), compared with those who had received antivirals after 48 hours (22%). Early antiviral treatment also was associated with lower rates of hospital admission and the need for mechanical ventilation, the authors reported.
In a multivariate analysis model, delayed antiviral treatment was independently associated with increased risk of ICU admission (odds ratio 3.03), as was presence of diabetes (OR 2.18).
Of the 237 patients, 10 (4%) died at a median of 15 days after symptom onset, including 8 who received delayed antiviral treatment, according to the findings. Neither transplant type nor specific immunosuppressive regimen was associated with poor outcome, the authors wrote.
“The most important finding was that starting antiviral treatment within 48 hours of symptom onset was associated with a decrease in admission to hospital and ICU, need for mechanical ventilation, and death,” the authors wrote. “This finding was consistent across many related outcome measures and reinforces the importance of early treatment with antiviral drugs in this susceptible population.”
In an accompanying editorial, Dr. Per Ljungman of Karolinska University Hospital, Stockholm, discussed “one important limitation” to the conclusion regarding early antiviral therapy in this and other at-risk, immunocompromised populations: the development of resistance.
“Although the rates of oseltamivir resistance have, until now, been low with the pandemic H1N1 strain, the development of new anti-influenza drugs should be a priority.” Additionally, he stressed, “Vaccination is the key preventive measure against influenza and is recommended to immunocompromised patients both by health authorities and scientific organizations.” He acknowledged, however, the difficulties inherent in the production and distribution of vaccine to risk groups early enough, as well as the uptake of vaccination in high-risk populations (Lancet Infect. Dis. 2010 July 9 [doi:10.1016/S1473-3099(10)70136-5]).
Several authors of the study reported having received research grants from or been consultants to Roche, Adamas Pharmaceuticals, and Bristol-Myers Squibb. Dr. Ljungman reported having no conflicts.
Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
7月9日，《柳叶刀传染病》(Lancet Infectious Diseases)在线发表的一篇研究报告称，去年大流行性H1N1感染对于实体器官移植受者而言尤其凶险，尽管接受了早期抗病毒治疗的患者相对于没有接受这种治疗的患者，其病情更轻，预后也更好。
加拿大埃德蒙顿阿尔伯塔大学的Deepali Kumar博士及其同事写道，在一项多中心队列研究所纳入的受试者中，感染了这种甲型流感菌株的2/3以上的实体器官移植受者都需要住院治疗，并且有4%死于与流感相关的并发症。
研究者写道，对于在症状发作后48 h内即接受了抗病毒治疗的患者，其需要住院治疗或通气支持的可能性更低(Lancet Infect. Dis. 2010 July 9 [doi:10.1016/S1473-3099(10)70133-X])。
研究者分析了美国和加拿大26家移植中心在2009年4~12月经微生物学检查确诊的甲型流感病毒(H1N1)感染者的病历。研究者称，在所评价的237例病例中，有154例成年人，中位年龄47岁，以及83例儿童，中位年龄9岁。其中87例为肾移植患者，47例为肝移植患者，33例为肺移植患者，45例为心脏移植患者，5例为肠移植患者，其余20例则涉及其他器官。
作者报告称，器官移植后H1N1症状发作的中位时间为3.6年，所表现出来的最常见症状是咳嗽、发热、肌痛、流鼻涕、咽喉痛和头痛。
在有胸片或CT数据的230例患者中，73例的影像学检查结果符合肺炎的表现。在所有237例患者中，13例的痰液或支气管肺泡灌洗液中检出了细菌性病原体。其他并发症包括：8例患者并发了巨细胞病毒血症、4例中耳炎、2例鼻窦炎以及1例脑炎。
作者写道，整个患者队列的疫苗接种数据并不完整。他们指出，症状发作前“有记录的139例患者中有55例(40%)接种了2009~2010年季节性流感疫苗，177例患者中有20例(11%)接受了大流行性H1N1疫苗。”
作者写道，在这237例患者中，除14例外其余所有患者均接受了抗病毒治疗，以奥司他韦(oseltamivir)为主。有42%的患者是在症状发作后48 h内即接受了抗病毒治疗，29%是在48~96 h内开始接受抗病毒治疗，29%则在96 h后才开始治疗。
总共有70%的患者在症状发作后2天(中位时间)住院，16%在症状发作后5天(中位时间)被收治到重症监护室(ICU)。在需要收治到ICU的37例患者中，21例需要机械通气，通气支持的中位持续时间为12天。
作者报告称，对与入住ICU相关的因素进行单因素分析，结果显示，早期接受了抗病毒治疗的患者出现入住ICU这一结果的几率 (8%)低于那些在48 h后才开始接受抗病毒治疗的患者(22%)。早期抗病毒治疗还与住院率的降低以及机械通气需求的减少相关。
在多因素分析模型中，抗病毒治疗延迟与入住ICU的风险增加独立相关(比值比OR 3.03)，糖尿病也是一样(OR 2.18)。
结果显示，在这237例患者中，10例(4%)在症状发作后15天(中位时间)死亡，其中包括8例抗病毒治疗延迟的患者。作者写道，移植类型或特定的免疫抑制方案均与转归不良无关。
作者写道：“最重要的发现是，在症状发作后48 h内即开始抗病毒治疗与住院、入住ICU、需要机械通气以及死亡的发生率减少相关。这一发现与许多相关的结局指标相符，也进一步强调了早期使用抗病毒药物对于该易感人群的重要意义。”
瑞典斯德哥尔摩Karolinska大学医院的Per Ljungman博士在随刊编者按中讨论道，关于早期抗病毒治疗用于这一人群以及其他存在风险的免疫受损人群的结论存在“一个重要的局限性”：耐药的出现。
Ljungman博士说：“虽然到目前为止大流行性H1N1菌株对奥司他韦耐药的发生率还比较低，但目前最重要的任务是研制出新的抗流感药物。”此外，Ljungman博士还强调道：“接种疫苗是最主要的流感预防措施，卫生当局和科学组织均应建议免疫受损患者接种流感疫苗。”不过，他也承认，要及早对危险人群进行接种在疫苗的生产和发放上尚存在着固有的困难，而且高危人群中疫苗的使用也是一大问题(Lancet Infect. Dis. 2010 July 9 [doi:10.1016/S1473-3099(10)70136-5])。
该研究的数名作者声明接受了罗氏、Adamas制药公司和百时美-施贵宝提供的研究经费或担任其顾问。Ljungman博士声明无相关利益冲突。
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