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Clinical Characteristics and Outcomes of Influenza A Infection in Kidney Transplant Recipients: A Single-Center Experience
Clinical Characteristics and Outcomes of Influenza A Infection in Kidney Transplant Recipients: A Single-Center Experience F.C.A. Odongoa,*, L.S. Azevedob, E.D. Netob, H. Yeh-Lia, H. Caiaffac, and L.C. Pierrottia a Department of Infectious and Parasitic Diseases, Clinical Hospital, University of São Paulo, São Paulo, Brazil; bDepartment of Urology and Renal Transplant, Clinical Hospital, University of São Paulo, São Paulo, Brazil; and cLaboratory of Molecular Biology, Clinical Hospital, University of São Paulo, São Paulo, Brazil
ABSTRACT Background. Influenza virus infection can cause severe illness in certain high-risk groups. Solid organ and hematopoietic stem cell transplant recipients have been shown to present a greater risk for severe influenza and complications than the general population. Methods. Retrospective descriptive cohort study of the features and outcomes of influenza infection in renal transplant recipients from July 2009 to May 2014. Results. Thirty-one patients were diagnosed with influenza A infection within the specified period. The incidence of influenza A was 26.5 cases/1,000 person-years. Hospital admission (68%), secondary bacterial pneumonia (68%), intensive care unit admission (14%), and mortality rate (14%) were higher than reported for immunocompetent patients. Conclusions. Influenza diagnosis and treatment should be prompt in immunocompromised patients to reduce the risk of complications. Patients who require intensive care owing to respiratory and hemodynamic complications present high mortality rates.
I
NFLUENZA is an acute, usually self-limited illness in healthy adults, but influenza virus infection can cause severe illness in certain high-risk groups. Individuals considered to be at high risk for severe disease include pregnant women, the very young or very old, immunocompromised people, and those with chronic underlying medical comorbidities [1]. One study found that 54.4% of the patients hospitalized during the 2009 H1N1 pandemic had at least one comorbid condition: chronic pulmonary disease, chronic heart disease, chronic renal failure, chronic liver failure, diabetes mellitus, immunosuppression, HIV/AIDS, transplant recipient, cancer, or obesity. Reported complications included viral pneumonia in 43.2% and secondary bacterial infection in 7.6%. Severe disease occurred in 12.8%, and 2.2% of those with severe illness required intensive care. Significant risk factors for severe illness were age <50 years, chronic comorbidities, morbid obesity, and bacterial coinfection. Early oseltamivir therapy was protective in 68% of the patients [2]. Solid organ and hematopoietic stem cell transplant recipients have been shown to present a greater risk for severe influenza and complications than the general population ª 2016 Published by Elsevier Inc. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 48, 2315e2318 (2016)
[3e6]. In these immunocompromised hosts, influenza virus infection more commonly caused asymptomatic viral shedding, antiviral resistance, and lower tract respiratory disease [6]. Multicenter studies have reported pneumonia rates ranging from 30% to 40% in solid organ transplant recipients with influenza. Hospital admissions as well as mortality rates are also substantially higher than in immunocompetent patients: 16%e17.5% and 7%, respectively [3,4]. Allograft rejection has been reported as a complication of influenza virus infection, with one of the first reports published in 1972 [7]. It is postulated that influenza virus causes a general stimulation of the host cell-mediated immunity [7,8]. Recent studies have shown allograft rejection in a variety of transplant patients even without reduction of the immunosuppressive treatment: lung, renal, liver, and pancreas transplants [9,10]. Shock and multiple organ
*Address correspondence to Fatuma Catherine Atieno Odongo, Av Dr Enéas de Carvalho Aguiar, 255, Divisão de Moléstias Infecciosase4 andar, CEP 05403-900, São PauloeSP, Brazil. E-mail: [email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.06.024
2315
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ODONGO, AZEVEDO, NETO ET AL
involvement similar to bacterial sepsis can occur in severe influenza [11]. Rare complications, such as fulminant myocarditis and encephalitis, have also been reported to occur in adults [11,12]. Neuraminidase inhibitors are the mainstay of influenza treatment in immunocompromised patients. Oseltamivir is well tolerated and has been shown to reduce disease duration and severity among patients [13]. Empirical antiviral treatment should be started on suspicion of influenza virus infection, regardless of symptom duration, to maximize benefits [3,14,15]. Nosocomial transmission of influenza virus has been shown to occur, so strict prevention measures must be followed by caregivers and relatives visiting transplant recipients [16]. Complete immunization is recommended for transplant candidates, their household contacts, and health care workers before transplantation. Annual inactivated influenza vaccine is recommended before and after transplantation for all patients [14,17]. The efficacy of the influenza vaccine is reduced in immunocompromised hosts compared with healthy adults [18]. Low rates of seroconversion and seroprotection have been demonstrated in renal transplant recipients, and this may predispose to influenza virus infection [18e21]. Some kidney transplant patients develop influenza infection despite annual vaccination [22]. Therefore, in addition to immunization of transplant recipients and their household contacts, chemoprophylaxis with the use of oseltamivir for 10 days is a valid preventive strategy in transplant recipients after exposure to a confirmed case [14]. The aim of the present study was to assess the clinical characteristics and outcomes of influenza A infection in renal transplant patients. METHODS This was a retrospective descriptive cohort study of the features and outcomes of influenza infection in renal transplant recipients
with influenza A infection from July 2009 to May 2014. All patients were followed at the Renal Transplant Unit of the Clinical Hospital of the University of São Paulo. We reviewed electronic medical records for data collection. Patients with incomplete medical data were excluded. Results were presented by means of descriptive parameters. Numeric variables were expressed as means, standard deviations, and ranges and categoric variables as percentage frequencies.
RESULTS
Thirty-one patients had influenza A virus infection within the specified period. Thirty patients had PCR-confirmed influenza A, and 1 patient was presumed to have pandemic H1N1 influenza disease. The incidence of influenza A was 26.5 cases/1,000 person-years. Three patients were excluded from the assessment owing to missing data. Two of the remaining 28 patients had 2 episodes of influenza A in the period. Infection was mainly acquired in autumn (75%) compared with winter (25%). Male patients were the majority (68%), and most patients (79%) were on triple immunosuppressive therapy with the use of tacrolimus, prednisone, and mycophenolate mofetil. The mean age at influenza diagnosis was 44.7 14.2 years. The mean period from transplantation to influenza virus infection was 4.5 4.5 years. Seven patients (25%) presented influenza within 90 days after transplantation, with the earliest infection occurring on the 6th day while the patient was still hospitalized, suggesting nosocomial transmission. Vaccination
Self-reported influenza vaccination in the previous year was higher (9/28, 32%) than confirmed vaccination (6/28, 21%). Vaccination status in the remaining patients was unknown. The mean time between vaccination and influenza virus infection was 14 9.4 days. Only 1 patient (4%) reported pneumococcal vaccination in the previous 5 years.
Table 1. Demographic and Clinical Characteristics of Deceased Patients
Sex
Symptom Duration
Time Between Hospital Admission and Death
3d
1d
7d
10 d
Prednisone, tacrolimus, mycophenolate
3d
10 d
Prednisone, tacrolimus, mycophenolate
7d
3d
Age (y)
Immunosuppressive Therapy
Male
24
Male
59
Prednisone, leflunomide, rapamycin Prednisone, tacrolimus, mycophenolate
Female
60
Female
66
Comorbidities
Chronic graft dysfunction, ectodermal dysplasia Hypertension, previous cerebral stroke Hypertension, type 2 diabetes mellitus, obesity, heart failure, hypothyroidism, nephrotic syndrome Hypertension, type 2 diabetes mellitus, previous acute myocardial infarction with myocardial revascularization
Complications
Septic shock. respiratory distress Respiratory distress, Klebsiella pneumoniae and streptococcus pneumoniae bacteremia Septic shock, respiratory distress
Alveolar hemorrhage
INFLUENZA A IN KIDNEY TRANSPLANT RECIPIENTS
2317
Nasopharyngeal swab and polymerase chain reaction (PCR) was the method of diagnosis. Influenza A was subtyped as pandemic H1N1 in 17 (63%) of the 27 patients with PCR confirmation. One patient with non-H1N1 influenza was diagnosed with Pneumocystis jirovecii and cytomegalovirus coinfections.
of adherence issues did not take the medication but recovered from the infection. Duration of antiviral treatment was registered for 25 patients. Based on follow-up PCR results and clinical evolution, treatment lasted 7 days in 10 (40%), 8e15 days in 11 (44%), and >15 days in 4 (16%). Empirical bacterial treatment was mainly levofloxacin in 7 (36.8%) and ceftriaxone plus clarithromycin in 5 (26.3%).
Clinical Characteristics
CONCLUSION
Symptoms were registered for 25 patients (89%). The most common symptoms were: cough (24, 96%), fever (19, 76%), shortness of breath (10, 40%), malaise (9, 36%), running nose (9, 36%), myalgia (8, 32%), sore throat (6, 24%), and headache (6, 24%). Gastrointestinal symptoms were reported by fewer patients: diarrhea (4, 16%), nausea and vomiting (3, 12%), and weight loss (2, 8%). Some patients complained of oliguria (12%), chills/excessive sweating (12%), and retro-orbital pain (4%).
The complication rates were higher than those reported for immunocompetent patients. Patients with severe disease who required intensive care due to respiratory and hemodynamic complications presented a 100% mortality rate. Advanced age and chronic diseases (present in 75% of the deceased) may have contributed to the severity of influenza. Influenza diagnosis and treatment should be prompt in immunocompromised patients to reduce the risk of complications. Influenza should be investigated in transplant recipients with respiratory symptoms irrespective of the vaccination history.
Influenza A Virus Infection
Radiologic Imaging
X-ray or computerized tomographic (CT) scan was available for 25 (89%) of the 28 patients. The most common CT scan abnormality was ground glass opacities in 90% (9/10), and 50% (5/10) also had micronodules. Pleural effusion and consolidation were reported for 16% (4/25) and 36% (9/25) of the x-rays and CT scans. X-ray abnormalities were rarely reported by the attending physicians. Laboratory Exams
Of the 28 patients, 26 (93%) underwent laboratory testing. Lymphopenia (<1,000 cells/m3) was present in 16 (62%) and leukocytosis or left shift in 15 (58%). Most patients had elevated C-reactive protein (88%). Creatinine levels were increased from baseline in 8 (31%). Clinical Outcomes/Complications
Secondary bacterial infection was diagnosed in 19 (68%) of the patients. Bacterial culture was not performed to identify bacterial pneumonia. Presumed diagnosis was based on clinical evolution, C-reactive protein levels, and white blood cell abnormalities. Hospital admission was necessary in 19 (68%). Both the incidence of admission to the intensive care unit and the general mortality rate were 14%. Respiratory distress was present in all of the patients admitted to the intensive care unit, where the mortality rate was 100% (Table 1). Only 1 deceased patient had confirmation of influenza vaccination in the previous year. One patient (4%) suffered acute graft failure and loss. Follow-up PCR was done for 16 patients. The mean viral elimination period was 9.2 days (range, 4e22 days). Treatment
Oseltamivir was prescribed for all 28 patients on presentation to the hospital. Of these, 27 patients (96%) followed the physician’s prescription, whereas 1 patient with a history
REFERENCES [1] World Health Organization. Influenza virus infections in humans. February 2014. Available at: http://www.who.int/influenza/human_ animal_interface/virology_laboratories_and_vaccines/influenza_virus_ infections_humans_feb14.pdf. Accessed December 14, 2015. [2] Viasus D, Pano-Pardo JR, Pachón J, et al. Factors associated with severe disease in hospitalized adults with pandemic (H1N1) 2009 in Spain. Clin Microbiol Infect 2011;17:738e46. [3] Kumar D, Michaels MG, Morris MI, et al. Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study. Lancet Infect Dis 2010;10: 521e6. [4] Vilchez RA, McCurry K, Dauber J, et al. S. Influenza virus infection in adult solid organ transplant recipients. Am J Transplant 2002;2:287e91. [5] Nichols WG, Guthrie KA, Corey L, Boeckh M. Influenza infections after hematopoietic stem cell transplantation: risk factors, mortality, and the effect of antiviral therapy. Clin Infect Dis 2004;39:1300e6. [6] Memoli MJ, Athota R, Reed S, et al. The natural history of influenza infection in the severely immunocompromised vs immunocompromised hosts. Clin Infect Dis 2014;58:214e24. [7] Briggs JD, Timbury MC, Paton AM, et al. Viral infection and transplant rejection. BMJ 1972;4:520. [8] Katerinis I, Hadaya K, Duquesnoy R, et al. De novo antiHLA antibody after pandemic H1N1 and seasonal influenza immunization in kidney transplant recipients. Am J Transplant 2011;11:1727e33. [9] Low CY, Kee T, Chan KP, et al. Pandemic (H1N1) 2009 infections in adult solid organ transplant recipients in Singapore. Transplantation 2010;90:1016e20. [10] Cordero E, Perez-Romero P, Moreno A, et al. Pandemic influenza A (H1N1) virus infection in solid organ transplant recipients: impact of viral and nonviral co-infection. Clin Microbiol Infect 2012;18:67e73. [11] Liao YC, Hsieh YC, Chang WC, et al. Fulminant myocarditis in an adult with 2009 pandemic influenza A (H1N1 influenza) infection. J Chin Med Assoc 2011;74:130e3. [12] Asadi-Pooya AA, Yaghoubi E, Nikseresht A, et al. The neurological manifestations of H1N1 influenza infection; diagnostic challenges and recommendations. Iran J Med Soc 2011;36: 36e9.
2318 [13] Treanor JJ, Hayden FD, Vrooman SP, et al. Efficacy and safety of the neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. JAMA 2000;283: 1016e24. [14] Kumar D, Morris MI, Kotton SN, et al. Guidance on novel influenza A/H1N1 in solid organ transplant recipients. Am J Transplant 2010;10:18e25. [15] Aoki FY, Macleod MD, Paggiaro P, et al. Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother 2003;51:123e9. [16] Zapata R, Uribe M, Martínez W, et al. Severe novel H1N1 influenza A infection in the immediate postoperative period of a liver transplant patient. Liver Transpl 2010;16: 447e52. [17] Danziger-Isakov L, Kumar D. AST Infectious Diseases Community of Practice. Vaccination in solid organ transplantation. Am J Transplant 2013;13:311e7.
ODONGO, AZEVEDO, NETO ET AL [18] Miraglia JL, Abdala E, Hoff PM, et al. Immunogenicity and reactogenicity of 2009 influenza A(H1N1)pdm09 inactivated monovalent nonadjuvanted vaccine in elderly and immunocompromised patients. PLoS One 2011;6:e27214. [19] Azevedo LS, Gerhard J, Miraglia JL, et al. Seroconversion of 2009 pandemic influenza A(H1N1)pdm09 vaccination in kidney transplant patients and the influence of different risk factors. Transpl Infect Dis 2013;15:612e8. [20] Fairhead T, Hendren E, Tinckam K, et al. Poor seroprotection but allosensitization after adjuvanted pandemic influenza H1N1 vaccine in kidney transplant recipients. Transpl Infect Dis 2012;14:575e83. [21] Smith KGC, Isbel NM, Catton MG, et al. Suppression of the humoral immune response by mycophenolate mofetil. Nephrol Dial Transplant 1998;13:160e4. [22] Freitas TVS, Ono G, Correa L, et al. Clinical manifestations and evolution of infection by influenza A (H1N1) in kidney transplant recipients. J Bras Nefrol 2011;33:136e41.
ABSTRACT Background. Influenza virus infection can cause severe illness in certain high-risk groups. Solid organ and hematopoietic stem cell transplant recipients have been shown to present a greater risk for severe influenza and complications than the general population. Methods. Retrospective descriptive cohort study of the features and outcomes of influenza infection in renal transplant recipients from July 2009 to May 2014. Results. Thirty-one patients were diagnosed with influenza A infection within the specified period. The incidence of influenza A was 26.5 cases/1,000 person-years. Hospital admission (68%), secondary bacterial pneumonia (68%), intensive care unit admission (14%), and mortality rate (14%) were higher than reported for immunocompetent patients. Conclusions. Influenza diagnosis and treatment should be prompt in immunocompromised patients to reduce the risk of complications. Patients who require intensive care owing to respiratory and hemodynamic complications present high mortality rates.
I
NFLUENZA is an acute, usually self-limited illness in healthy adults, but influenza virus infection can cause severe illness in certain high-risk groups. Individuals considered to be at high risk for severe disease include pregnant women, the very young or very old, immunocompromised people, and those with chronic underlying medical comorbidities [1]. One study found that 54.4% of the patients hospitalized during the 2009 H1N1 pandemic had at least one comorbid condition: chronic pulmonary disease, chronic heart disease, chronic renal failure, chronic liver failure, diabetes mellitus, immunosuppression, HIV/AIDS, transplant recipient, cancer, or obesity. Reported complications included viral pneumonia in 43.2% and secondary bacterial infection in 7.6%. Severe disease occurred in 12.8%, and 2.2% of those with severe illness required intensive care. Significant risk factors for severe illness were age <50 years, chronic comorbidities, morbid obesity, and bacterial coinfection. Early oseltamivir therapy was protective in 68% of the patients [2]. Solid organ and hematopoietic stem cell transplant recipients have been shown to present a greater risk for severe influenza and complications than the general population ª 2016 Published by Elsevier Inc. 230 Park Avenue, New York, NY 10169
Transplantation Proceedings, 48, 2315e2318 (2016)
[3e6]. In these immunocompromised hosts, influenza virus infection more commonly caused asymptomatic viral shedding, antiviral resistance, and lower tract respiratory disease [6]. Multicenter studies have reported pneumonia rates ranging from 30% to 40% in solid organ transplant recipients with influenza. Hospital admissions as well as mortality rates are also substantially higher than in immunocompetent patients: 16%e17.5% and 7%, respectively [3,4]. Allograft rejection has been reported as a complication of influenza virus infection, with one of the first reports published in 1972 [7]. It is postulated that influenza virus causes a general stimulation of the host cell-mediated immunity [7,8]. Recent studies have shown allograft rejection in a variety of transplant patients even without reduction of the immunosuppressive treatment: lung, renal, liver, and pancreas transplants [9,10]. Shock and multiple organ
*Address correspondence to Fatuma Catherine Atieno Odongo, Av Dr Enéas de Carvalho Aguiar, 255, Divisão de Moléstias Infecciosase4 andar, CEP 05403-900, São PauloeSP, Brazil. E-mail: [email protected] 0041-1345/16 http://dx.doi.org/10.1016/j.transproceed.2016.06.024
2315
2316
ODONGO, AZEVEDO, NETO ET AL
involvement similar to bacterial sepsis can occur in severe influenza [11]. Rare complications, such as fulminant myocarditis and encephalitis, have also been reported to occur in adults [11,12]. Neuraminidase inhibitors are the mainstay of influenza treatment in immunocompromised patients. Oseltamivir is well tolerated and has been shown to reduce disease duration and severity among patients [13]. Empirical antiviral treatment should be started on suspicion of influenza virus infection, regardless of symptom duration, to maximize benefits [3,14,15]. Nosocomial transmission of influenza virus has been shown to occur, so strict prevention measures must be followed by caregivers and relatives visiting transplant recipients [16]. Complete immunization is recommended for transplant candidates, their household contacts, and health care workers before transplantation. Annual inactivated influenza vaccine is recommended before and after transplantation for all patients [14,17]. The efficacy of the influenza vaccine is reduced in immunocompromised hosts compared with healthy adults [18]. Low rates of seroconversion and seroprotection have been demonstrated in renal transplant recipients, and this may predispose to influenza virus infection [18e21]. Some kidney transplant patients develop influenza infection despite annual vaccination [22]. Therefore, in addition to immunization of transplant recipients and their household contacts, chemoprophylaxis with the use of oseltamivir for 10 days is a valid preventive strategy in transplant recipients after exposure to a confirmed case [14]. The aim of the present study was to assess the clinical characteristics and outcomes of influenza A infection in renal transplant patients. METHODS This was a retrospective descriptive cohort study of the features and outcomes of influenza infection in renal transplant recipients
with influenza A infection from July 2009 to May 2014. All patients were followed at the Renal Transplant Unit of the Clinical Hospital of the University of São Paulo. We reviewed electronic medical records for data collection. Patients with incomplete medical data were excluded. Results were presented by means of descriptive parameters. Numeric variables were expressed as means, standard deviations, and ranges and categoric variables as percentage frequencies.
RESULTS
Thirty-one patients had influenza A virus infection within the specified period. Thirty patients had PCR-confirmed influenza A, and 1 patient was presumed to have pandemic H1N1 influenza disease. The incidence of influenza A was 26.5 cases/1,000 person-years. Three patients were excluded from the assessment owing to missing data. Two of the remaining 28 patients had 2 episodes of influenza A in the period. Infection was mainly acquired in autumn (75%) compared with winter (25%). Male patients were the majority (68%), and most patients (79%) were on triple immunosuppressive therapy with the use of tacrolimus, prednisone, and mycophenolate mofetil. The mean age at influenza diagnosis was 44.7 14.2 years. The mean period from transplantation to influenza virus infection was 4.5 4.5 years. Seven patients (25%) presented influenza within 90 days after transplantation, with the earliest infection occurring on the 6th day while the patient was still hospitalized, suggesting nosocomial transmission. Vaccination
Self-reported influenza vaccination in the previous year was higher (9/28, 32%) than confirmed vaccination (6/28, 21%). Vaccination status in the remaining patients was unknown. The mean time between vaccination and influenza virus infection was 14 9.4 days. Only 1 patient (4%) reported pneumococcal vaccination in the previous 5 years.
Table 1. Demographic and Clinical Characteristics of Deceased Patients
Sex
Symptom Duration
Time Between Hospital Admission and Death
3d
1d
7d
10 d
Prednisone, tacrolimus, mycophenolate
3d
10 d
Prednisone, tacrolimus, mycophenolate
7d
3d
Age (y)
Immunosuppressive Therapy
Male
24
Male
59
Prednisone, leflunomide, rapamycin Prednisone, tacrolimus, mycophenolate
Female
60
Female
66
Comorbidities
Chronic graft dysfunction, ectodermal dysplasia Hypertension, previous cerebral stroke Hypertension, type 2 diabetes mellitus, obesity, heart failure, hypothyroidism, nephrotic syndrome Hypertension, type 2 diabetes mellitus, previous acute myocardial infarction with myocardial revascularization
Complications
Septic shock. respiratory distress Respiratory distress, Klebsiella pneumoniae and streptococcus pneumoniae bacteremia Septic shock, respiratory distress
Alveolar hemorrhage
INFLUENZA A IN KIDNEY TRANSPLANT RECIPIENTS
2317
Nasopharyngeal swab and polymerase chain reaction (PCR) was the method of diagnosis. Influenza A was subtyped as pandemic H1N1 in 17 (63%) of the 27 patients with PCR confirmation. One patient with non-H1N1 influenza was diagnosed with Pneumocystis jirovecii and cytomegalovirus coinfections.
of adherence issues did not take the medication but recovered from the infection. Duration of antiviral treatment was registered for 25 patients. Based on follow-up PCR results and clinical evolution, treatment lasted 7 days in 10 (40%), 8e15 days in 11 (44%), and >15 days in 4 (16%). Empirical bacterial treatment was mainly levofloxacin in 7 (36.8%) and ceftriaxone plus clarithromycin in 5 (26.3%).
Clinical Characteristics
CONCLUSION
Symptoms were registered for 25 patients (89%). The most common symptoms were: cough (24, 96%), fever (19, 76%), shortness of breath (10, 40%), malaise (9, 36%), running nose (9, 36%), myalgia (8, 32%), sore throat (6, 24%), and headache (6, 24%). Gastrointestinal symptoms were reported by fewer patients: diarrhea (4, 16%), nausea and vomiting (3, 12%), and weight loss (2, 8%). Some patients complained of oliguria (12%), chills/excessive sweating (12%), and retro-orbital pain (4%).
The complication rates were higher than those reported for immunocompetent patients. Patients with severe disease who required intensive care due to respiratory and hemodynamic complications presented a 100% mortality rate. Advanced age and chronic diseases (present in 75% of the deceased) may have contributed to the severity of influenza. Influenza diagnosis and treatment should be prompt in immunocompromised patients to reduce the risk of complications. Influenza should be investigated in transplant recipients with respiratory symptoms irrespective of the vaccination history.
Influenza A Virus Infection
Radiologic Imaging
X-ray or computerized tomographic (CT) scan was available for 25 (89%) of the 28 patients. The most common CT scan abnormality was ground glass opacities in 90% (9/10), and 50% (5/10) also had micronodules. Pleural effusion and consolidation were reported for 16% (4/25) and 36% (9/25) of the x-rays and CT scans. X-ray abnormalities were rarely reported by the attending physicians. Laboratory Exams
Of the 28 patients, 26 (93%) underwent laboratory testing. Lymphopenia (<1,000 cells/m3) was present in 16 (62%) and leukocytosis or left shift in 15 (58%). Most patients had elevated C-reactive protein (88%). Creatinine levels were increased from baseline in 8 (31%). Clinical Outcomes/Complications
Secondary bacterial infection was diagnosed in 19 (68%) of the patients. Bacterial culture was not performed to identify bacterial pneumonia. Presumed diagnosis was based on clinical evolution, C-reactive protein levels, and white blood cell abnormalities. Hospital admission was necessary in 19 (68%). Both the incidence of admission to the intensive care unit and the general mortality rate were 14%. Respiratory distress was present in all of the patients admitted to the intensive care unit, where the mortality rate was 100% (Table 1). Only 1 deceased patient had confirmation of influenza vaccination in the previous year. One patient (4%) suffered acute graft failure and loss. Follow-up PCR was done for 16 patients. The mean viral elimination period was 9.2 days (range, 4e22 days). Treatment
Oseltamivir was prescribed for all 28 patients on presentation to the hospital. Of these, 27 patients (96%) followed the physician’s prescription, whereas 1 patient with a history
REFERENCES [1] World Health Organization. Influenza virus infections in humans. February 2014. Available at: http://www.who.int/influenza/human_ animal_interface/virology_laboratories_and_vaccines/influenza_virus_ infections_humans_feb14.pdf. Accessed December 14, 2015. [2] Viasus D, Pano-Pardo JR, Pachón J, et al. Factors associated with severe disease in hospitalized adults with pandemic (H1N1) 2009 in Spain. Clin Microbiol Infect 2011;17:738e46. [3] Kumar D, Michaels MG, Morris MI, et al. Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study. Lancet Infect Dis 2010;10: 521e6. [4] Vilchez RA, McCurry K, Dauber J, et al. S. Influenza virus infection in adult solid organ transplant recipients. Am J Transplant 2002;2:287e91. [5] Nichols WG, Guthrie KA, Corey L, Boeckh M. Influenza infections after hematopoietic stem cell transplantation: risk factors, mortality, and the effect of antiviral therapy. Clin Infect Dis 2004;39:1300e6. [6] Memoli MJ, Athota R, Reed S, et al. The natural history of influenza infection in the severely immunocompromised vs immunocompromised hosts. Clin Infect Dis 2014;58:214e24. [7] Briggs JD, Timbury MC, Paton AM, et al. Viral infection and transplant rejection. BMJ 1972;4:520. [8] Katerinis I, Hadaya K, Duquesnoy R, et al. De novo antiHLA antibody after pandemic H1N1 and seasonal influenza immunization in kidney transplant recipients. Am J Transplant 2011;11:1727e33. [9] Low CY, Kee T, Chan KP, et al. Pandemic (H1N1) 2009 infections in adult solid organ transplant recipients in Singapore. Transplantation 2010;90:1016e20. [10] Cordero E, Perez-Romero P, Moreno A, et al. Pandemic influenza A (H1N1) virus infection in solid organ transplant recipients: impact of viral and nonviral co-infection. Clin Microbiol Infect 2012;18:67e73. [11] Liao YC, Hsieh YC, Chang WC, et al. Fulminant myocarditis in an adult with 2009 pandemic influenza A (H1N1 influenza) infection. J Chin Med Assoc 2011;74:130e3. [12] Asadi-Pooya AA, Yaghoubi E, Nikseresht A, et al. The neurological manifestations of H1N1 influenza infection; diagnostic challenges and recommendations. Iran J Med Soc 2011;36: 36e9.
2318 [13] Treanor JJ, Hayden FD, Vrooman SP, et al. Efficacy and safety of the neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. JAMA 2000;283: 1016e24. [14] Kumar D, Morris MI, Kotton SN, et al. Guidance on novel influenza A/H1N1 in solid organ transplant recipients. Am J Transplant 2010;10:18e25. [15] Aoki FY, Macleod MD, Paggiaro P, et al. Early administration of oral oseltamivir increases the benefits of influenza treatment. J Antimicrob Chemother 2003;51:123e9. [16] Zapata R, Uribe M, Martínez W, et al. Severe novel H1N1 influenza A infection in the immediate postoperative period of a liver transplant patient. Liver Transpl 2010;16: 447e52. [17] Danziger-Isakov L, Kumar D. AST Infectious Diseases Community of Practice. Vaccination in solid organ transplantation. Am J Transplant 2013;13:311e7.
ODONGO, AZEVEDO, NETO ET AL [18] Miraglia JL, Abdala E, Hoff PM, et al. Immunogenicity and reactogenicity of 2009 influenza A(H1N1)pdm09 inactivated monovalent nonadjuvanted vaccine in elderly and immunocompromised patients. PLoS One 2011;6:e27214. [19] Azevedo LS, Gerhard J, Miraglia JL, et al. Seroconversion of 2009 pandemic influenza A(H1N1)pdm09 vaccination in kidney transplant patients and the influence of different risk factors. Transpl Infect Dis 2013;15:612e8. [20] Fairhead T, Hendren E, Tinckam K, et al. Poor seroprotection but allosensitization after adjuvanted pandemic influenza H1N1 vaccine in kidney transplant recipients. Transpl Infect Dis 2012;14:575e83. [21] Smith KGC, Isbel NM, Catton MG, et al. Suppression of the humoral immune response by mycophenolate mofetil. Nephrol Dial Transplant 1998;13:160e4. [22] Freitas TVS, Ono G, Correa L, et al. Clinical manifestations and evolution of infection by influenza A (H1N1) in kidney transplant recipients. J Bras Nefrol 2011;33:136e41.