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Keywords:

  • influenza A;
  • H1N1;
  • cancer;
  • solid tumors

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. FUNDING SOURCES
  9. REFERENCES

BACKGROUND:

Pandemic influenza A (hereafter 2009/H1N1) caused significant morbidity and mortality during the 2009 pandemia. Patients with chronic medical conditions and immunosuppressive diseases had a greater risk of complications. However, data regarding the characteristics and outcome of 2009/H1N1 infection in patients with solid tumors are nonexistent. Herein, the authors describe a series of influenza 2009/H1N1 in patients with solid malignancies at 3 major cancer hospitals worldwide.

METHODS:

The authors retrospectively reviewed the records of patients with solid organ malignancies and 2009/H1N1 from The University of Texas M. D. Anderson Cancer Center in Houston, Texas; the Mexican National Cancer Institute, Federal District of Mexico; and King Hussein Cancer Center in Amman, Jordan from the period of the 2009 H1N1 pandemia. Data on demographics, disease characteristics, and outcome were extracted.

RESULTS:

In total, 115 cases were identified during the pandemic influenza among the 3 institutions. High rates of hospitalization (50%), pneumonia (23%), and death (9.5%) were reported. Patients who developed pneumonia and those who died were moderately to severely immunocompromised (P = .001 and P = .006, respectively). A multivariate competing risk analysis demonstrated that a delay >48 hours in starting antiviral therapy was associated significantly with an increased risk of developing pneumonia (P = .013).

CONCLUSIONS:

The 2009/H1N1 pandemic caused severe illness in immunocompromised patients with cancer who had solid tumors, and heavily immunosuppressed patients were at greater risk of developing pneumonia and death. Early initiation of antiviral therapy is crucial in this patient population to decrease morbidity and probably mortality. Cancer 2012. © 2012 American Cancer Society.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. FUNDING SOURCES
  9. REFERENCES

Pandemic influenza A 2009/H1N1 was first reported causing illnesses in Mexico in March 2009. The virus then rapidly spread to the United States and worldwide. On April 17, 2009, the Centers for Disease Control and Prevention (CDC) reported the first 2 cases of this infection in 2 children in California.1 Two months later, the World Health Organization (WHO) declared it a global pandemic, and this pandemic concluded on June 23, 2010. The final H1N1 CDC statistics estimate that, between April 2009 and April 10, 2010, there were between 43 million and 89 million cases of 2009/H1N1 and between 195,000 and 403,000 2009/H1N1-related hospitalizations.2 Greater than half of patients who were admitted to the hospital with 2009/H1N1 infection were likely to have at least 1 underlying medical condition.3-5

Patients with chronic conditions, patients with immunosuppressant diseases like human immunodeficiency virus and cancer, transplantation recipients (solid organ and hematopoietic stem cell), pregnant women, obese individuals, and children all are reportedly at greater risk of complications.6-11 Data regarding the characteristics and outcome of 2009/H1N1 infection in patients with solid tumors are nonexistent. The objective of this report was to describe the results from a retrospective, multicenter study of the epidemic in cancer patients with solid tumors who presented with acute respiratory illnesses compatible with influenza infection and were recently infected with influenza A virus (probable and confirmed 2009/H1N1 virus) at 3 major comprehensive cancer centers worldwide.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. FUNDING SOURCES
  9. REFERENCES

We searched the microbiology databases for all patients with solid tumors who had influenza A infection diagnosed during the 2009/2010 H1N1 pandemia at 3 major cancer hospitals worldwide: The University of Texas M. D. Anderson Cancer Center (MDACC), Houston, Tex; the Mexican National Cancer Institute (Instituto Nacional de Cancerologia [INCan], Mexico Federal District; and the King Hussein Cancer Center (KHCC), Amman, Jordan.

We collected the following data from the electronic medical records for all patients: demographics (age, sex, and race), cancer type, comorbidities and concurrent coinfections, use of immunosuppressive therapy, use of antiviral prophylaxis, clinical presentation, radiologic characteristics, treatment, and outcome. All patients were followed until resolution of all signs and symptoms of infection or death. The median follow-up for patients who survived was 136 days (range, 1-472 days).

Definitions

A case of influenza infection was defined as a patient with cancer who had a solid tumor, was cared for at any of the 3 institutions, and developed an acute respiratory illness confirmed by a positive viral culture, and/or a positive direct fluorescence antigen test, and/or a positive polymerase chain reaction (PCR) test for the influenza virus during the 2009/H1N1 pandemic. The infection was classified as community acquired if the onset of symptoms was before hospitalization, or within the first 2 days after admission, or as nosocomial if the symptoms developed anytime after that during hospitalization. Upper respiratory tract infection was defined as the onset of rhinorrhea, nasal/sinus congestion, otitis media, pharyngitis, or cough with or without expectoration and was confirmed by positive direct immunofluorescence (DFA), viral culture, or PCR from nasal wash with a clear chest x-ray or computed tomography (CT) scan of the chest. Lower respiratory infection was defined as new or changing pulmonary infiltrates by chest x-ray or CT scans suggestive of viral etiology (ie, interstitial infiltrates or ground-glass opacities) and a positive DFA, viral culture, or PCR from respiratory samples, including nasal wash, endotracheal tube aspirate, sputum, and bronchoalveolar lavage fluid. Clinical outcomes were classified as either complete recovery, progression to pneumonia/lower respiratory infection, or death within 60 days from the onset of symptoms. Recovery was defined as the resolution of all clinical manifestations of influenza infection irrespective of viral shedding. A concurrent coinfection was considered when another organism was isolated within 3 days of diagnosis of an influenza infection.

Neutropenia was defined as an absolute neutrophil count of <500 cells/mL, and severe lymphopenia was defined as an absolute lymphocyte count of ≤200 cells/mL. Obesity was defined as a body mass index (BMI) (calculated as the weight in kilograms divided by the square of the height in meters [kg/m2]) of ≥30 kg/m2 in adults aged ≥18 years or a BMI percentile of ≥95 in children between ages 2 years and 18 years. Severe immunodeficiency was defined as the presence of 2 or more of the following criteria: an absolute leukocyte count <200 cells/mL or an absolute neutrophil count <500 cells/mL, use of immunosuppressive therapy (cytotoxic chemotherapy, immunosuppressive drugs, immunomodulators, radiotherapy, or corticosteroids), all within 2 weeks before the diagnosis of influenza A infection. Moderate immunodeficiency was defined as the presence of only 1 criterion of severe immunodeficiency or when 2 or more of the following criteria were present: an a absolute lymphocyte count between 200 and 1000 cells/mL or an absolute neutrophil count between 500 and 1000 cells/mL within 2 weeks before the diagnosis of influenza A infection and immunosuppressive therapy (as defined above) within 1 month before the diagnosis of the infection. Mild immunodeficiency was defined as the presence of only 1 criterion of moderate immunodeficiency. If none of the criteria listed above were present, then the patient was considered to have no immunodeficiency. Although these criteria for immunodeficiency are not validated but are known as risk factors for different types of infections, we elected to use them for risk stratification in this patient population.

Statistical Considerations

Chi-square tests or Fisher exact tests were used for categorical data analysis. Continuous variables were compared by using Wilcoxon rank-sum tests. Survival analysis was performed on patients' pneumonia development and survival after symptom onset. First, a competing risk analysis with death as a competing event was performed to assess the cumulative incidence curves of pneumonia development for the patients who received antiviral treatment within 48 hours of their symptoms onset and those who did not. The curves also were compared between these 2 groups of patients. Then, a multiple competing risk analysis was performed to identify the independent risk factors for developing pneumonia. Similarly, Kaplan-Meier survival curves were assessed for the patients who received antiviral treatment within 48 hours of their symptoms onset and those who did not. A log-rank test was used to compare the survival of these 2 groups. Then, Cox proportional hazards regression was used to identify the independent risk factors for patients' mortality. All statistical analyses were performed using SAS version 9.1 software (SAS Institute Inc., Cary, NC). The institutional review boards at all 3 institutions approved the study, informed consent was waived, no patient contact was made, and patient confidentiality was protected.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. FUNDING SOURCES
  9. REFERENCES

In total, 115 cases were identified during the pandemic influenza among the 3 institutions (26 at INCan in Mexico, 69 at KHCC in Jordan, and 20 at MDACC in the United States). Table 1 indicates that the median patient age was 40 years (age range, 1-79 years). The most common underlying malignancies were breast cancer (24%) followed by central nervous system malignancies (11%), sarcoma (8%), and bone cancer (7%). All patients presented with influenza-like symptoms: 90% had fever, 85% had cough, 57% had rhinorrhea or nasal congestion, 37% had a sore throat, 31% had myalgia, and 29% had dyspnea (Table 2). Fifty-eight patients required hospital admission, and their median length of stay was 5 days (range, 1-33 days). Eighty-one patients (70%) received chemotherapy within 1 month of acquiring the infection, and 18 patients (16%) were receiving steroids. It is noteworthy that 32 patients (28%) were considered obese.

Table 1. Baseline Characteristics of Cancer Patients With Pandemic Influenza A (2009/H1N1) Infection (n = 115)
CharacteristicNo. of Patients/Total (%)
  • Abbreviations: BMI, body mass index; WHO, World Health Organization; y, years.

  • a

    BMI was measured in patients aged ≥18 years (n = 73).

  • b

    Obesity was defined as a BMI ≥30 kg/m2 in adults aged ≥18 years or a BMI percentile of 95 to 100 in children between ages 1 year and 18 years.

Age, y 
 Median [range]40 [1-79]
 Age group, y 
  0-519 (17)
  6-1825 (22)
  19-5035 (30)
  >5028 (24)
  >648 (7)
Sex 
 Male47 (41)
 Female68 (59)
Ethnic group 
 Non-Hispanic white9 (8)
 Black3 (3)
 Hispanic30 (26)
 Middle Eastern71 (62)
 Other2 (2)
Immunodeficiency status 
 None42 (37)
 Mild30 (26)
 Moderate29 (25)
 Severe14 (12)
Cancer status 
 Active52 (45)
 Remission59 (51)
 Relapse4 (4)
Immunosuppressive therapy at time of diagnosis86 (75)
 Systemic chemotherapy81 (70)
 Radiation therapy28 (24)
 Corticosteroids16 (14)
BMI, kg/m2a 
 Median [range]28.0 [15.0-54.0]
 WHO classification, kg/m2 
  Underweight: ≤18.52/73 (3)
  Normal range: 18.5-24.9920/73 (27)
  Overweight: 25-29.9922/73 (30)
  Obese: ≥3029/73 (40)
 Obesityb32 (28)
Table 2. Clinical Manifestations, Treatment, and Outcome of Pandemic Influenza A (2009/H1N1) Infection in Patients With Cancer (n = 115)
CharacteristicNo. of Patients/Total No. (%)
  1. Abbreviations: ANC, absolute neutrophil count; d, days; ICU, intensive care unit; WBC white blood cell count.

Symptoms 
 Fever102/113 (90)
 Cough98 (85)
 Nasal congestion65 (57)
 Sore throat42 (37)
 Myalgias36 (31)
 Shortness of breath33 (29)
 Nausea/vomiting11 (10)
 Diarrhea16 (14)
 Weakness29 (25)
Duration of symptoms before presentation: Median [range], d2 [1-21]
Infection type 
 Upper respiratory tract infection88 (77)
 Pneumonia27 (23)
Laboratory abnormalities on presentation 
 Leukocytosis: WBC >11,000/mm311/105 (10)
 Severe neutropenia: ANC <500 cells/mL10/105 (10)
 Severe lymphopenia: Absolute lymphocyte count <200 cells/mL7/105 (7)
 Elevated creatinine: >1.3 mg/dL10/91 (11)
 Decreased albumin: <3.5 g/dL48/83 (58)
Admission to the hospital58 (50)
Length of stay: Median [range], d5 [1-33]
ICU admission 
 On admission7 (6)
 Later2/114 (2)
Mechanical ventilation9 (8)
Treatmenta 
 Oseltamivir100 (87)
 None15 (13)
Mortality11 (9.5)

Table 3 provides a comparison among the patients at the 3 institutions. Other than ethnicity, there were no significant differences between them. However, patients at KHCC in Jordan were less immunocompromised and had lower mortality.

Table 3. Comparison of Clinical Characteristics and Outcome Among the 3 Institutions
 No. of Patients (%)
CharacteristicMDACC, n = 20KHCC, n = 69INCan, n = 26
  • Abbreviations: d, days; ICU, intensive care unit; INCan, National Cancer Institute (Federal District of Mexico, Mexico); KHCC, King Hussein Cancer Center (Amman, Jordan); MDACC, The University of Texas M. D. Anderson Cancer Center (Houston, Tex); y, years.

  • a

    Obesity was defined as a body mass index (BMI) ≥30 kg/m2 in adults aged ≥18 years or a BMI percentile of 95 to 100 in children between ages 1 year and 18 years.

Age: Median [range], y31 [3-79]18 [1-67]55 [38-77]
Sex   
 Male9 (45)34 (49)4 (15)
 Female11 (55)35 (51)22 (85)
Ethnic group   
 Non-Hispanic white9 (45)0 (0)0 (0)
 Black3 (15)0 (0)0 (0)
 Hispanic4 (20)0 (0)26 (100)
 Middle Eastern2 (10)69 (100)0 (0)
 Asiatic2 (10)0 (0)0 (0)
Immunodeficiency status   
 None4 (20)30 (43)8 (31)
 Mild6 (30)18 (26)6 (23)
 Moderate7 (35)13 (19)9 (35)
 Severe3 (15)8 (12)3 (11)
Cancer status   
 Active14 (70)20 (29)18 (69)
 Remission3 (15)48 (70)8 (31)
 Relapse3 (15)1 (1)0 (0)
Immunosuppressive therapy at time of diagnosis
 Systemic chemotherapy10 (20)57 (83)14 (54)
 Radiation therapy1 (5)24 (35)3 (12)
 Corticosteroids3 (15)11 (16)2 (8)
Obesitya6 (30)17 (25)9 (35)
Duration of symptoms before presentation: Median [range], d2 [1-7]2 [1-21]2 [1-8]
Infection type   
 Upper respiratory tract  infection16 (80)58 (84)14 (54)
 Pneumonia4 (20)11 (16)12 (46)
Admission to the hospital10 (50)31 (45)17 (65)
Length of stay: Median [range], d5 [1-11]4 [1-23]6 [2-32]
ICU admission2 (10)5 (7)2 (8)
Mechanical ventilation2 (10)5 (7)2 (8)
Treatment   
 Oseltamivir13 (65)68 (99)19 (73)
 None7 (35)1 (1)7 (27)
Mortality2 (10)4 (6)5 (19)

Pneumonia

Twenty-seven patients (23%) developed pneumonia, including 25 on presentation (Table 4). The median age of these 27 patients was 46 years (age range, 1-77 years). Compared with patients who had influenza infection limited to the upper respiratory tract, patients who had pneumonia were older (median age, 46 years vs 35 years), were moderately to severely immunosuppressed (70% vs 27%), presented significantly later to the hospital after symptom onset (median, 3 days [range, 1-21 days] vs 2 days [range 1-21 days]; P < .001), and subsequently had a significantly longer time from symptom onset to the initiation of antiviral therapy (median, 3 days [range, 1-24 days] vs 2 days [range, 1-21 days]; P < .001). Furthermore, patients who began antiviral therapy more than 48 hours after symptom onset had a greater risk of developing pneumonia (Table 4).

Table 4. Risk Factors for Progression to Pneumonia or Death in Patients With Cancer and Pandemic Influenza A (2009/H1N1) Infection
 PneumoniaDeath
 No. of Patients (%)PNo. of Patients (%)P
CharacteristicYes, n = 27No, n = 88Univariate AnalysisMultiple Competing Risk AnalysisYes, n = 11No, n = 104Univariate AnalysisCox Regression Analysis
Age, y        
 Median [range], y46 [1-77]35 [1-79]  45 [5-77]38 [1-79]  
 Age group  .022   .1 
  0-51 (4)18 (20)  1 (9)18 (17)  
  6-185 (19)20 (23)  1 (9)24 (23).6 
  19-5010 (37)25 (28).16 4 (36)31 (30)  
  >5011 (41)25 (28)  5 (45)31 (30)  
Immunodeficiency status        
 None-mild8 (30)64 (73)<.0001.0011 (9)71 (68)<.001.006
 Moderate-severe19 (70)24 (27)  10 (91)33 (32)  
Immunosuppressive therapy at the time of diagnosis22 (81)64 (73).36 10 (91)76 (73).29 
Obesity7 (26)25 (28).8 1 (9)31 (30).29 
Time from start of symptoms to presentation: Median [range], d3 [1-21]2 [0-21]<.001 2 [1-8]2 [0-21].23 
Time from onset of symptoms to initiation of therapy: Median [range], d3 [1-24]2 [0-21]<.0001 3 [1-11]2 [0-24].03 
Treatment within 48 h of symptoms7/25 (28)59/81 (73)<.0001.0134/11 (36)62/95 (65).1 

A multiple competing risk analysis indicated that the degree of immunosuppression (moderate to severe) at the time of diagnosis and antiviral therapy received >48 hours after symptom onset were associated independently with the development of pneumonia in cancer patients with solid tumors (P = .001 and P = .013, respectively).

Treatment

Most patients received a neuraminidase inhibitor, mainly oseltamivir. Patients who did not receive antiviral therapy were considered to have mild infection, and all of these latter patients completely recovered.

A univariate competing risk analysis (Fig. 1) indicated that patients who received treatment within 48 hours of symptom onset had less risk of developing pneumonia (P < .001), which was confirmed by a multiple competing risk analysis. A log-rank test (Fig. 2) indicated that patients had a trend toward increased mortality if therapy was initiated >48 hours after symptom onset (P = .06). However, a Cox proportional hazards regression analysis indicated that this factor was not associated independently with mortality.

thumbnail image

Figure 1. These are cumulative incidence curves for the development of pneumonia in patients who did and did not receive antiviral therapy within 48 hours of symptom onset in a competing risk analysis using death as a competing event (P < .001).

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thumbnail image

Figure 2. These are Kaplan-Meier survival curves for patients who did and did not receive antiviral therapy within 48 hours of symptom onset (P = .06; log-rank test).

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Outcome

The mortality rate from 2009/H1N1 infection in these cancer patients was 9.5% (11 of 115 patients) for all patients. For patients with pneumonia, the mortality rate was 30% (8 of 27 patients), and the median time to death was 12.5 days (range, 9-31 days) after presentation to the hospital (data not shown). All fatalities were secondary to respiratory failure. Compared with patients who survived 2009/H1N1 infection, those who died were moderately to severely immunosuppressed (P < .01) and had a significantly longer time from the onset of symptoms to the initiation of antiviral therapy (median, 3 days [range, 1-11 days] vs 2 days [range, 0-2 days]; P < .03). A Cox proportional hazards regression indicated that the degree of immunosuppression (moderate to severe) at the time of diagnosis was the only independent factor associated with mortality among cancer patients with solid tumors (P = .006).

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. FUNDING SOURCES
  9. REFERENCES

The 2009/H1N1 pandemic concluded on June 23, 2010. Although the majority of infected patients recovered without complications, patients with pre-existing medical conditions, such as immunosuppressed cancer patients, usually are included in reports as hospitalized and critically ill and are believed to be at greater risk of complications.11-13

Several important conclusions can be drawn from our study, which, to our knowledge, is the first multicenter study to date describing 2009/H1N1 infection in patients with solid tumors during the pandemic. First, this virus caused severe illness in immunocompromised cancer patients with solid tumors, resulting in relatively high rates of hospitalization (50%), pneumonia (23%), and death (9.5%). Second, the majority of infected cancer patients were aged <50 years and were either moderately or severely immunosuppressed. Finally, a 48-hour delay in receiving antiviral therapy was associated with an increased risk of developing pneumonia and a trend toward greater mortality.

An initial distinctive epidemiologic feature of the 2009/H1N1 pandemic was the shift in the age distribution to a younger population.11, 14 One of the first studies indicated that 60% of the cases occurred in patients aged <18 years.13 Conversely, age has been identified as a risk factor for the development of severe disease in hematopoietic stem cell transplantation (HSCT) recipients.8 In our study, we observed that 38.2% of the cases occurred in individuals aged ≤18 years, only 7% occurred in individuals aged ≥65 years, and age was not correlated with a worse prognosis. Although, in general, most patients with cancer belong to an older population, there was a low rate of infection in the elderly population, as expected, because they may have partial immunity from former infections with H1N1 influenza viruses.13, 15, 16

Obesity has been reported as a new risk factor for adverse outcomes after infection with pandemic2009/H1N1 viruses.11, 14 We observed a high percentage of obese cancer patients with influenza A infection (36%) and with a trend toward developing pneumonia (P = .08). This finding is surprising, because unintentional weight loss is a particularly common problem in cancer patients on active chemotherapy.

Pneumonia is a major complication from influenza A infection. Among hospitalized patients in Mexico, the reported rate of pneumonia among patients with 2009/H1N1 infections was 18%,9 which was similar to the rate reported for pregnant women with 2009/H1N1 in the United States.17 Among immunocompromised patients, rates reportedly are higher in HSCT recipients and solid organ transplantation (SOT) recipients (range, 32%-55%).6, 8, 18, 19 We observed a 23% incidence of pneumonia among our patients with solid tumors.5 The majority of these cancer patients needed critical care support, and almost one-third died (30%). Most patients who developed pneumonia were receiving immunosuppressive therapy at the time of diagnosis, and they sought medical care later, with a subsequent delay in initiating antiviral therapy. This latter factor contributed significantly to morbidity and possibly to mortality.

The CDC estimates that, during the pandemic, approximately 12,470 2009/H1N1-related deaths occurred from a total of 61 million cases in the United States. Only 1670 deaths occurred in individuals aged >65 years, confirming epidemiologic data indicating that this infection affects the younger population more frequently and more severely. We observed a high mortality rate (9.5%) from this infection in patients with solid tumors, higher than that reported for SOT recipients (4%) and similar to that reported for HSCT recipients (between 6% and 16%).6, 8, 18

Antiviral therapy, mainly neuraminidase inhibitors, started within 48 hours of illness onset reduces the duration of symptoms and improves outcome for healthy individuals with influenza A.20 Patients with severe 2009/H1N1 infection who were admitted to an intensive care unit in Michigan had an estimated median delay of 8 days (range, 5-12 days) from illness onset to the initiation of antiviral therapy.13 Risk factors for pneumonia that have been identified in immunosuppressed populations are a delay in early initiation of antiviral therapy in HSCT and SOT recipients6, 8 and lymphopenia in HSCT recipients.6 In our patients with solid organ malignancies, we observed that the degree of immunosuppression and a delay >48 hours in the start of neuraminidase inhibitors were associated with progression to pneumonia and a trend toward increased mortality. These data underscore the importance of early diagnosis and the institution of empiric antiviral therapy pending microbiologic confirmation of influenza infection in immunocompromised patients.

Our study has several limitations. First, because it was a retrospective, observational study, no control group was available. Second, some of the cases were not confirmed as secondary to 2009/H1N1 virus by PCR (mainly cases from MDACC), but the CDC reports that 90% of the influenza infection cases during the 2009 influenza season were identified as involving the 2009/H1N1 influenza A virus.9, 21, 22 Unlike small case series, however, our study included patients from different geographic locations, giving us a worldwide perspective of the disease in this population and providing a better basis for the subsequent generalization of our findings.

In summary, during a pandemic, influenza A infection may present as a severe disease in patients with solid tumors, as it does in other immunocompromised patients (HSCT recipients and SOT recipients). Heavily immunosuppressed patients are at greater risk of developing pneumonia with subsequent high mortality. A delay in the initiation of antiviral therapy is associated with a greater risk of developing of pneumonia. Early suspicion and initiation of therapy within 48 hours are crucial in this patient population to decrease morbidity.

Acknowledgements

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. FUNDING SOURCES
  9. REFERENCES

We thank to Ms. Cheryl Perego, Sherry Cantu, Polly Williams, Cindy Good, Linda Graviss, Kim Nguyen, and Susan Conley for their invaluable work during the 2009/H1N1 pandemia and Michael Worley for his editorial support.

FUNDING SOURCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. FUNDING SOURCES
  9. REFERENCES

No specific funding was disclosed.

CONFLICT OF INTEREST DISCLOSURES

Roy F. Chemaly has received financial research funding from Roche and GSK. Dr. Karen J. Vigil has received financial research funding from Merck.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. Acknowledgements
  8. FUNDING SOURCES
  9. REFERENCES
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