Oseltamivir Therapy Research Articles

Persistence of pandemic influenza H1N1 virus in young patients after oseltamivir therapy in the 2009–2010 season: a comparison with seasonal H1N1 with or without H275Y mutation

Comparison of the viral persistence of pandemic H1N1 (H1N1pdm) and seasonal H1N1 with or without H275Y mutation after oseltamivir therapy has not been adequately done. Virus was isolated before and on days 4-6 from the start of oseltamivir treatment for 158 cases of seasonal (2007-2008 and 2008-2009 seasons) or pandemic (2009-2010 season) H1N1 influenza. Sequence analysis was done for each season and NA inhibition assay (IC(50)) was done in the 2009-2010 season. H275Y mutation before therapy was 0% in the 2007-2008 and 2009-2010 seasons, but 100% in the 2008-2009 season. Fever and other symptoms were noticeably prolonged after oseltamivir therapy for children with H275Y mutated seasonal H1N1 (2008-2009 season), but not in patients with seasonal H1N1 without mutation (2007-2008) or H1N1pdm (2009-2010). The viral persistence rate was significantly higher for patients 15 years or younger than for those 16 years and older with H275Y mutated seasonal H1N1 (46.2% and 10.5%, respectively) or with H1N1pdm (43.3% and 11.5%, respectively). The H275Y mutation emerged after oseltamivir treatment in 2.4% (2/82) of all patients with H1N1pdm. In two children, the H275Y mutation emerged after therapy and the IC(50) increased more than 200 fold; however, the prolongation of fever was not so prominent. In conclusion, oseltamivir was effective for fever and other clinical symptoms; however, the virus persisted longer than expected after treatment in H1N1pdm influenza-infected children in the 2009-2010 season, similar to seasonal H1N1 with H275Y mutation in the 2008-2009 season.

Relapse of minimal change disease following infection with the 2009 pandemic influenza (H1N1) virus

We report a case of relapse of minimal change disease following infection with the influenza A (H1N1) virus responsible for the 2009 pandemic. A 22-year-old man who had been diagnosed with minimal change disease presented with systemic edema. He had achieved complete remission with an oral steroid (prednisolone 1mg/kg/day) by the 17th day of administration. On the 27th day of prednisolone administration, he presented with a new onset of generalized edema after several days of productive coughing. His urine showed proteinuria (4+) with a protein/creatinine ratio (PCR) of 2852.1mg/g. His nasal swab sample was positive for the 2009 pandemic influenza (H1N1) virus by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). He received oseltamivir (150mg/day) for 5days. A day after completing the oseltamivir therapy, his proteinuria returned to a normal range; urinalysis was negative for protein with PCR 79.2mg/g. One month later, the patient remained normal with no proteinuria.

Oseltamivir overuse at a Chicago hospital during the 2009 influenza pandemic and the poor predictive value of influenza-like illness criteria

We report on the overuse of oseltamivir at Rush University Medical Center, Chicago during the 2009 H1N1 influenza pandemic. Of 210 patients with suspected influenza who underwent respiratory virus reverse transcription polymerase chain reaction (RT-PCR) testing, 113 (54%) received empiric oseltamivir therapy. However, only 50 treated patients (44%) had laboratory confirmed 2009 H1N1. Factors associated with oseltamivir use included a younger median age (including age < 5 y), subjective fever, cough, rhinorrhea, myalgias, higher median temperature, and fulfilment of the US Centers For Disease Control and Prevention (CDC) influenza-like illness (ILI) criteria. However, on multivariate analysis, only subjective fever (p = 0.006, odds ratio (OR) 3.1, 95% confidence interval (CI) 1.4-6.7) and fulfilment of CDC ILI criteria (p = 0.001, OR 3.6, 95% CI 1.7-7.5) were significantly associated with the receipt of oseltamivir. The CDC ILI criteria had a poor positive predictive value of 43% (95% CI 33.3-53.3) for 2009 H1N1. While the ILI criteria are a useful epidemiologic tool, it is too imprecise for direct patient care.

Clinical Features, Oseltamivir Treatment and Outcome in Infants Aged &lt;12 Months with Laboratory-Confirmed Influenza a in 2009

Data on the use of oseltamivir in infants is limited. We documented the clinical presentations of infants aged <12 months hospitalized with laboratory-confirmed influenza A in the southern hemisphere winter of 2009 and compared outcomes in relation to oseltamivir therapy. Data were extracted from prospectively collected and collated influenza case reports (June-September 2009) ascertained through Paediatric Active Enhanced Disease Surveillance, an in-patient surveillance system operating at the Children's Hospital at Westmead (CHW), Sydney, NSW, Australia. Nosocomial cases were excluded. Of 56 infants with definite influenza (35 pandemic H1N1 2009) admitted to the CHW, 20 were treated with oseltamivir. Overall, 12 (60%) of those treated with oseltamivir were aged <6 months. Cough, fever and coryza were the most common clinical features (≥70%). Vomiting was present on admission in 31.4%. All 7 cases presenting with vomiting then given antiviral treatment had reduction of vomiting and the other 13 did not develop vomiting on treatment. There were three infants with hypoxaemia (oxygen saturation ≤93%) on presentation in the treatment group compared with none in the control group (P=0.04). The median duration of hospital stay was the same in both groups (2.5 days). The use of oseltamivir was well tolerated in hospitalized infants. Vomiting, one of the widely reported side effects of oseltamivir, was found to be more a presenting symptom of influenza than a side effect of oseltamivir. Based on pulse oximetry, oseltamivir-treated cases may have been more severe on presentation, but there was no significant difference in length of hospital stay.

Pneumonia Complicating Pandemic (H1N1) 2009

We performed an observational analysis of a prospective cohort of adults hospitalized for pandemic (H1N1) 2009 at 13 Spanish hospitals, from June to November 2009, to determine the risk factors, clinical features, and outcomes of pneumonia. Of 585 patients requiring hospitalization, chest radiography was obtained in 542. A total of 234 (43.1%) patients had pneumonia, of whom 210 underwent bacterial microbiologic studies. Of these patients, 174 (82.8%) had primary viral pneumonia and 36 (17.2%) had concomitant/secondary bacterial pneumonia. Bilateral pneumonia occurred in 48.3% of patients. Streptococcus pneumoniae was the most frequent pathogen among patients with bacterial pneumonia (26 of 36 patients). None of them had received pneumococcal vaccine. Compared with patients without pneumonia, those with pneumonia more frequently had shock during hospitalization (9.8% vs. 1%; p < 0.001), required intensive care unit admission (22.6% vs. 5.8%; p < 0.001), underwent mechanical ventilation (17.9% vs. 3.2%; p < 0.001), and had longer length of hospital stay (median, 7 d vs. 5 d; p < 0.001). In-hospital mortality was higher in patients with pneumonia than in the others (5.2% vs. 0%; p < 0.001). Absence of comorbid conditions (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.32-3.24) was found to be an independent risk factor for pneumonia, whereas early (≤ 48 h) oseltamivir therapy (OR, 0.29; 95% CI, 0.19-0.46) was a protective factor. In conclusion, pneumonia is a frequent complication among adults hospitalized for pandemic (H1N1) 2009 and causes significant morbidity. Mortality in pandemic (H1N1) 2009 is low, but occurs mainly in patients with pneumonia. Early oseltamivir therapy is a protective factor for this complication.

Acute immune thrombocytopenic purpura in an adolescent with 2009 novel H1N1 influenza A virus infection

Although both leukopenia and thrombocytopenia are not uncommon hematological findings among patients with novel 2009 H1N1 influenza virus infection, immune thrombocytopenic purpura has rarely been shown to be associated with this novel influenza A infection. Here, we describe a previously healthy adolescent who presented with fever, influenza-like symptoms and acute onset of generalized petechiae and active oral mucosa bleeding on the third day of his illness. Severe leukopenia and thrombocytopenia were found. There was neither malignancy nor blast cells found by bone marrow aspiration. Real-time reverse transcriptase polymerase chain reaction was positive for novel 2009 H1N1 influenza infection. Novel influenza-associated atypical immune thrombocytopenic purpura was diagnosed. The patient recovered uneventfully after oseltamivir and methylprednisolone therapy.

Oseltamivir-resistant pandemic A(H1N1) 2009 influenza viruses detected through enhanced surveillance in the Netherlands, 2009–2010

Enhanced surveillance of infections due to the pandemic A(H1N1) influenza virus, which included monitoring for antiviral resistance, was carried out in the Netherlands from late April 2009 through late May 2010. More than 1100 instances of infection with the pandemic A(H1N1) influenza virus from 2009 and 2010 [A(H1N1) 2009] distributed across this period were analyzed. Of these, 19 cases of oseltamivir-resistant virus harboring the H275Y mutation in the neuraminidase (NA) were detected. The mean 50% inhibitory concentration (IC50) levels for oseltamivir- and zanamivir-susceptible A(H1N1) 2009 viruses were 1.4-fold and 2-fold, respectively, lower than for the seasonal A(H1N1) influenza viruses from 2007/2008; for oseltamivir-resistant A(H1N1) 2009 virus the IC50 was 2.9-fold lower. Eighteen of the 19 patients with oseltamivir-resistant virus showed prolonged shedding of the virus and developed resistance while on oseltamivir therapy. Sixteen of these 18 patients had an immunodeficiency, of whom 11 had a hematologic disorder. The two other patients had another underlying disease. Six of the patients who had an underlying disease died; of these, five had received cytostatic or immunosuppressive therapy. No indications for onward transmission of resistant viruses were found. This study showed that the main association for the emergence of cases of oseltamivir-resistant A(H1N1) 2009 virus was receiving antiviral therapy and having drug-induced immunosuppression or an hematologic disorder. Except for a single case of a resistant virus not linked to oseltamivir therapy, the absence of detection of resistant variants in community specimens and in specimens from contacts of cases with resistant virus suggested that the spread of resistant A(H1N1) 2009 virus was limited. Containment may have been the cumulative result of impaired NA function, successful isolation of the patients, and prophylactic measures to limit exposure.

Risk factors for prolonged shedding of 2009 H1N1 influenza virus

This retrospective study was conducted to estimate the shedding of 2009 H1N1 virus and the risk analysis by review of medical charts, laboratory and radiological findings of all inpatients with confirmed pandemic influenza A (H1N1) at a provincial pediatric hospital. A total of 41 cases attending the inpatient department between 15 November, 2009 to 14 December, 2009 were included. Prolonged and discontinuous shedding of 2009 H1N1 virus (median, 10 days; range, 2 to 24 days) were detected by real-time RT-PCR. The interval from onset of symptom to the start of oseltamivir therapy was an independent risk factor for prolonged virus shedding.

Clinical Features of Pneumonia Caused by 2009 Influenza A(H1N1) Virus in Beijing, China

BackgroundData on symptoms and radiographic changes in patients with pandemic 2009 influenza A(H1N1) (A[H1N1]) pneumonia during convalescence have not been reported.MethodsDuring October 26, 2009, and January 23, 2010, adult patients with pneumonia with laboratory-confirmed or clinically suspected A(H1N1) infections were observed for clinical characteristics, high-resolution chest CT scan, and lung function test changes during acute and 3-month convalescent phases.ResultsOf the 65 case subjects, the median age was 41 (interquartile range [IQR], 28-57) years, 60.0% were men, and 55.4% had at least one underlying medical condition. Sixty-two patients started oseltamivir therapy within a median of 5 (IQR, 4-6) days from the onset of illness, and 31 received IV corticosteroids. ARDS developed in 33 patients, and 24 were treated initially with noninvasive positive pressure ventilation (NPPV). In this group, NPPV was successful in 13 patients (54.2%). Nine patients died at a median of 16 (IQR, 10-24) days after onset of illness. Multivariate Cox regression identified two independent risk factors for death: progressive dyspnea after resolution of fever (relative risk, 5.852; 95% CI, 1.395-24.541; P = .016) and a higher APACHE (Acute Physiology and Chronic Health Evaluation) II score on presentation (relative risk for each point, 1.312; 95% CI, 1.140-1.511; P < .001). At 3-month follow-up of survivors with A(H1N1), ground-glass opacities were still present, although diminished, in 85.7%, and diffusing capacity for carbon monoxide was mildly reduced in 61.5%.ConclusionsGround-glass opacities and decreased diffusing capacity were the main abnormalities observed at 3-month follow-up of survivors of A(H1N1).

Factors associated with severe disease in hospitalized adults with pandemic (H1N1) 2009 in Spain

The risk factors for complications in patients with influenza A (H1N1)v virus infection have not been fully elucidated. We performed an observational analysis of a prospective cohort of hospitalized adults with confirmed pandemic influenza A (H1N1)v virus infection at 13 hospitals in Spain, between June 12 and November 10, 2009, to identify factors associated with severe disease. Severe disease was defined as the composite outcome of intensive‐care unit (ICU) admission or in‐hospital mortality. During the study period, 585 adult patients (median age 40 years) required hospitalization because of pandemic (H1N1) 2009. At least one comorbid condition was present in 318 (54.4%) patients. Pneumonia was diagnosed in 234 (43.2%) patients and bacterial co‐infection in 45 (7.6%). Severe disease occurred in 75 (12.8%) patients, of whom 71 required ICU admission and 13 (2.2%) died. Independent factors for severe disease were age <50 years (OR, 2.39; 95% CI, 1.05–5.47), chronic comorbid conditions (OR, 2.93; 95% CI, 1.41–6.09), morbid obesity (OR, 6.7; 95% CI, 2.25–20.19), concomitant and secondary bacterial co‐infection (OR, 2.78; 95% CI, 1.11–7) and early oseltamivir therapy (OR, 0.32; 95% CI 0.16–0.63). In conclusion, although adults hospitalized for pandemic (H1N1) 2009 suffer from significant morbidity, mortality is lower than that reported in the earliest studies. Younger age, chronic comorbid conditions, morbid obesity and bacterial co‐infection are independent risk factors for severe disease, whereas early oseltamivir therapy is a protective factor.

Oseltamivir-resistant Influenza A and B Viruses Pre- and Postantiviral Therapy in Children and Young Adults With Cancer

Immunocompromised patients are highly susceptible to influenza infection and can have prolonged viral shedding, which is a risk factor for the development of antiviral resistance. We investigated the emergence of oseltamivir-resistant influenza variants in children and young adults with cancer during the 2002-2008 influenza seasons. The demographic and clinical features of influenza infections in 12 patients who had viral isolates obtained before and after oseltamivir therapy was initiated were studied. Antiviral susceptibilities were determined by the fluorescence-based neuraminidase (NA) enzyme inhibition assay and by sequencing genes encoding NA and matrix M2 proteins. The mean age of patients was 10.5 (range, 1.1-23.0) years. Ten patients had hematologic malignancies, 4 were recipients of hematopoietic stem cell transplants, and all patients were receiving immunosuppressive therapy. Eleven patients had prolonged respiratory symptoms and 8 had prolonged viral shedding. Serial viral isolates were available for 8 of 12 patients. Oseltamivir-resistant influenza viruses were isolated from 4 children (3 influenza A [H3N2] and 1 influenza B virus): before the initiation of antiviral therapy in 2 patients and during therapy in the other 2 patients. Three resistant influenza A (H3N2) viruses shared a common E119V NA mutation. One patient was infected with oseltamivir-resistant influenza B virus (IC50, 731.86 ± 155.12 nM) that harbored a N294S NA mutation, the first report of this mutation in influenza B viruses. Oseltamivir-resistant influenza viruses can exist before or rapidly emerge during antiviral therapy in immunocompromised individuals, and this has important implications for therapy and infection control.

Acute respiratory distress syndrome due to influenza virus A/H1N1v in a patient with HIV/HCV co-infection

The clinical severity of human infection with the novel influenza virus A/H1N1v has not been completely defined, especially in HIV/hepatitis C virus (HCV) infected patients. Although most patients develop mild to moderate symptoms, severe disease may occur in a limited proportion of cases. We report the case of a 44-year-old man infected with HIV and HCV with a high CD4 cell count who developed acute respiratory distress syndrome associated with influenza virus A/H1N1v infection. The patient recovered completely after oseltamivir therapy and mechanical ventilation.

Pandemic 2009 H1N1 Influenza in Patients with Hematopoietic Stem Cell Transplantation and Hematologic Malignancy: Single Center Experience

Although valuable information on many aspects of the pandemic 2009 H1N1 influenza came to light in a relatively short period of time, the disease course among immunocompromised patients is largely unknown. In this study, we present the results of active H1N1 surveillance in 32 patients who were treated at our hematology/stem cell transplantation clinic between December 2009 and January 2010. We also report the clinical and laboratory features of patients with laboratory-proven disease and try to define the impact of novel H1N1 disease on their outcome. Eight patients in the hematology clinic and 7 patients in the hematology/stem cell transplantation unit tested positive for pandemic H1N1 infection. Patients were treated with oral oseltamivir for 5–15 days. In 10 patients the infection was limited to the upper respiratory tract. But in 5 patients it was complicated with lower respiratory diseases. Three of them required intensive care support with mechanic ventilation and all died during follow-up. As the clinical and radiological findings of H1N1 infection are nonspecific in nature, we should have a high index of suspicion in immunocompromised patients. Therefore, beginning empiric oseltamivir therapy while waiting for laboratory results and increasing the dose/duration of therapy in laboratory-confirmed cases could be life saving.

Management of the 2009 A/H1N1 Influenza Pandemic in Patients with Hematologic Diseases: A Prospective Experience at an Italian Center

Data derived from epidemiologic surveillance adopted at our center in hematologic and stem cell transplant patients during the 2009 influenza A (H1N1)v pandemic are reported. Of the 52 patients with influenza-like disease we observed, 37 underwent a real-time PCR evaluation and 21 had a confirmed diagnosis. Of the RT-PCR-confirmed cases, 23.8% were children (age <18 years) and 9.5% were >65 years; 47.6% presented with a pulmonary infiltrate and 33.3% with respiratory failure. Pulmonary involvement was observed more frequently in patients with comorbidities. All patients received a course of oseltamivir therapy starting an average of 1 day (range <1–2) after the onset of symptoms. No patient was transferred to the intensive care unit. The viral disease had a generally favorable outcome despite the high frequency of pulmonary involvement. A prompt clinical evaluation with an early antiviral and supportive therapy may have played a beneficial role in the outcome.

The impact of the 2009 H1N1 influenza pandemic on pediatric patients with sickle cell disease

Respiratory infections are associated with clinically significant illness in patients with sickle cell disease (SCD). The 2009 H1N1 pandemic was perceived as a significant threat to this population. We undertook a chart review of all patients with SCD followed at our institution to identify those with confirmed H1N1 infection. Further chart and laboratory data was collected on affected patients to analyze clinical courses and the factors that correlated with disease severity. Approximately half of the patients with confirmed H1N1 infection were managed successfully on an outpatient basis with oseltamivir therapy. Among the patients admitted, the most common diagnosis was acute chest syndrome (ACS). Most admitted patients had uncomplicated clinical courses, with a median length of admission of 3 days and no mortality or requirement for mechanical ventilation. A past history of ACS or reactive airway disease correlated with a higher rate of admission and of ACS incidence during the acute illness. Chronic transfusion therapy or hydroxyurea therapy with high hemoglobin F levels had a strong inverse correlation with incidence of ACS. Our results indicate that that in general the impact of the H1N1 influenza pandemic on patients with SCD was mild but that past clinical history correlated with the severity of illness. Additionally, effective hydroxyurea therapy and chronic transfusion therapy appeared to be protective against the incidence of ACS. Our results suggest guidelines for the management of patients with SCD during future influenza pandemics as well as during seasonal influenza epidemics.

Influenza A (H1N1) virus‐induced hepatocellular injury in a kidney transplant patient

The swine-origin influenza A (H1N1) virus is mainly responsible for flu. No hepatitis attributable to H1N1 virus has been previously documented. Herein, we report on a kidney transplant patient who developed influenza H1N1 virus-induced hepatocellular injury. The patient's body temperature was only somewhat elevated, and pulmonary and flu symptoms were mild. H1N1 virus was detected by polymerase chain reaction assay in nasopharyngeal and bronchoalveolar swabs, as well as in the serum. The hepatocellular injury episode resolved after the patient had been placed on oseltamivir therapy. This observation suggests that acute hepatocellular injury could be linked to the influenza H1N1 virus.

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.

Critically Ill Patients with Pandemic Influenza A/H1N1 2009 at a Medical Center in Korea

Results: 27 patients with confirmed pandemic Influenza A/H1N1 2009 were admitted to the intensive care unit (ICU) at the Asan Medical Center (AMC). The median age (IQR) was 59 years (41∼67), and 66.7% of the patients were older than 51 years. A total of 81.5% of the patients had 2 or more co-morbidities. The median time (IQR) from symptom onset to presentation was 2 days (1∼4), and the median time from presentation to ICU admission was 0 days (0∼1.5). All patients received oseltamivir (300 mg/day) and 13 patients received triple combination therapy (oseltamivir, amantadine, ribavirin). Twelve patients required mechanical ventilation on the first day of ICU admission. A total of 6 patients (22.2%) died within 28 days of admission. The patients who died had significantly higher acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores at presentation. There were no significant differences in age, co-morbidities, or antiviral regimens between survivors and non-survivors. Conclusion: Critical illness related to pandemic Influenza A/H1N1 2009 was common in elderly patients with chronic co-morbidities. All patients were given high-dose oseltamivir or triple combination antiviral therapy. Nonetheless, patients with critical illnesses associated with pandemic Influenza A/H1N1 2009 had a death rate of 22.2%.

Características clínicas de pacientes con infección por Influenza A (H1N1) 2009 y patología crítica

Objective Retrospective, observational study in children hospitalized due to Influenza A (H1N1) between October 2009 and February 2010, emphasizing on those who required intensive therapy. Material and methods Risk factors, symptoms, course, complications, mortality, time of disappearance of RT-PCR Influenza A (H1N1), average length of stay and duration of treatment with oseltamivir, were studied, comparing critically ill patients (group I) with the rest of hospitalized patients (group II). Results A total of 38 children, with a mean age of 5.03 ± 4.6 years were admitted during the study period. Six patients required intensive care, 83.3% had risk factors for influenza A (H1N1) compared with 62.5% in group II. Fever > 38 °C was the predominant symptom (92.1%). Respiratory symptoms were significantly more frequent in group I (83.3% vs. 33.6; P < .01). Two critically ill patients required mechanical ventilation due to ARDS (acute respiratory distress syndrome). One patient with exacerbation of chronic respiratory failure responded favourably to high-flow oxygen. One patient developed fulminant myocarditis and required ECMO (Extracorporeal Membrane Oxygenation) because of secondary cardiogenic shock, which developed into multiple organ dysfunction and brain death. Oseltamivir therapy was given for an average of 8.6 days in group I and 4.5 days in group II ( P < .05), checking the negativity of RT-PCR Influenza A (H1N1) in 7 ± 2 days. The average stay was significantly higher in group I. Two patients admitted to PICU died. Conclusions The presence of risk factors increases the likelihood of unfavourable outcome: high mortality among patients requiring intensive care. Monitoring of RT-PCR Influenza A (H1N1) could help establish the duration of isolation measures.

Comparison of the clinical symptoms and the effectiveness of neuraminidase inhibitors for patients with pandemic influenza H1N1 2009 or seasonal H1N1 influenza in the 2007–2008 and 2008–2009 seasons

The clinical symptoms and effectiveness of neuraminidase inhibitors (NAI) have not been adequately compared among pandemic H1N1 2009 patients, seasonal H1N1 patients, and patients with H1N1 with the H275Y mutation. The data of 68 seasonal H1N1 patients in 2007-2008, 193 seasonal H1N1 patients in 2008-2009, and 361 pandemic H1N1 2009 patients diagnosed by PCR who received an NAI were analyzed. The duration of fever (body temperature ≥ 37.5 ºC) after the first dose of NAI and from onset was calculated. The H275Y neuraminidase mutation status was determined for 166 patients. Significantly lower mean age (18.4 ± 13.2 years) and a higher percentage of teenagers (53.7%) were found for pandemic 2009 influenza than for seasonal influenza (P < 0.001). The peak body temperature was equivalent (mean, 39.0 ºC) in the three seasons, and the frequency of symptoms was the same or lower for pandemic influenza compared with seasonal H1N1. None of the 34 analyzed pandemic H1N1 virus isolates contained the H275Y mutation, which was commonly detected in the 2008-2009 season. The duration of fever after the start of oseltamivir therapy was significantly shorter for patients with pandemic (23.0 ± 11.6 h) than with seasonal H1N1 in both the 2008-2009 (49.7 ± 32.3 h) and 2007-2008 seasons (32.0 ± 18.9 h). The mean duration of fever after the first dose of zanamivir was not different among the three seasons (26.9-31.5 h). Clinical symptoms were the same or somewhat milder, and oseltamivir was more effective, for pandemic 2009 than for seasonal H1N1 influenza with or without H275Y mutation.