Takashi Kawashima

Factors Influencing the Effectiveness of Oseltamivir and Amantadine for the Treatment of Influenza: A Multicenter Study from Japan of the 2002—2003 Influenza Season

BACKGROUND To evaluate the effectiveness of oseltamivir and amantadine for the treatment of influenza with respect to various clinical factors, a prospective multicenter study of the influenza season of 2002-2003 was done with 2163 patients whose condition was diagnosed by an antigen-detection test kit. METHODS Oseltamivir was administered to 803 patients with influenza A (A+Os group) and 684 patients with influenza B (B+Os group). Amantadine was administered to 676 patients with influenza A (A+Am group). RESULTS For each group, the duration of fever (i.e., body temperature, > or = 37.5 degrees C) was significantly shorter in patients who received the drug within 12 h after the onset of symptoms than in patients who received the drug > 12 h after the onset. For all 3 groups, the duration of fever was shorter in patients with a highest temperature < 39 degrees C than in patients with temperatures > or = 39 degrees C. The duration of fever was significantly longer for the B+Os group than for the A+Os group. Multiple regression analysis found that the type of influenza, the highest body temperature, and the time between the onset of symptoms and the start of treatment are independent factor that influence the duration of fever. CONCLUSIONS Early administration increases the benefit of anti-influenza drugs--not only the benefit of oseltamivir treatment for influenza A, but also the benefit of amantadine treatment for influenza A and oseltamivir treatment for influenza B. Oseltamivir may be less effective as a treatment for influenza B than for influenza A. A highest body temperature of > or = 39 degrees C was an indicator of a longer duration of fever.

Clinical Effectiveness of Oseltamivir and Zanamivir for Treatment of Influenza A Virus Subtype H1N1 with the H274Y Mutation: A Japanese, Multicenter Study of the 2007–2008 and 2008–2009 Influenza Seasons

BACKGROUND Influenza A virus subtype H1N1 with the H274Y mutation emerged and spread worldwide. However, the clinical effectiveness of the neuraminidase inhibitors, oseltamivir and zanamivir, has not been adequately reevaluated. METHODS Data from 164 patients with H1N1 virus infection and 59 patients with H3N2 virus infection during the 2008-2009 influenza season and 68 patients with H1N1 virus infection during the 2007-2008 influenza season who received a neuraminidase inhibitor were analyzed. The duration of fever (body temperature 37.5 degrees C) after the first dose of oseltamivir or zanamivir and from onset of symptoms was calculated from patient reports. The influenza virus was isolated, and its subtype was determined by hemagglutinin inhibition assay and polymerase chain reaction. The H274Y neuraminidase mutation status was determined by sequencing the neuraminidase segment. RESULTS Of 68 patients with H1N1 virus infection during the 2007-2008 season, 41 were treated with oseltamivir, and 27 were treated with zanamivir. During the 2008-2009 season, 77 patients with H1N1 virus infection were treated with oseltamivir, and 87 were treated with zanamivir; 31 and 28 patients with H3N2 virus infection were treated with oseltamivir and zanamivir, respectively. All 49 analyzed H1N1 virus isolates obtained during the 2008-2009 season, but none of the isolates obtained during the 2007-2008 season, contained the H274Y mutation. The mean +/- standard deviation duration of fever after the start of oseltamivir therapy was significantly longer for patients with H1N1 virus infection (49.1+/-30.2 h) than it was for patients with H3N2 virus infection (33.7+/-20.1 h; P < .01) during the 2008-2009 season and patients with H1N1 virus infection during the 2007-2008 season (32.0+/-18.9 h; P < .001). The duration of fever was significantly longer after the first dose of oseltamivir than it was after the first dose of zanamivir for patients with H1N1 virus infection during the 2008-2009 season (P <.001). The duration of fever from onset of H1N1 virus infection was significantly longer for children 15 years of age during 2008-2009 (70.6+/-34.5 h) than it was for such children during 2007-2008 (48.4+/-21.2). CONCLUSION The effectiveness of oseltamivir, but not that of zanamivir, decreased significantly for H1N1 virus infection during the 2008-2009 season.

Clinical effectiveness of oseltamivir for influenza A(H1N1) virus with H274Y neuraminidase mutation

OBJECTIVE To evaluate the clinical effectiveness of oseltamivir therapy started within 48h of the onset for influenza A(H1N1) virus with H274Y neuraminidase (NA) mutation. METHODS Virus was isolated before and four to six days after starting oseltamivir treatment from 73 outpatients with influenza A(H1N1) virus in the 2007-2008 and 2008-2009 seasons. NA inhibition assays (IC(50)) and sequence analyses were done using influenza viruses isolated from these patients. Body temperature was evaluated before and on the second, third, and fourth days after starting treatment. RESULTS H274Y mutation was not shown in the 2007-2008 season (44 patients) and shown in all 29 patients in the 2008-2009 season by NA sequence analyses. The mean IC(50) before oseltamivir treatment was significantly higher in 2008-2009 (319.3+/-185.4 nM) than in 2007-2008 (1.5+/-0.8 nM; p<.001). Patients < or =15 years with oseltamivir-resistant virus infection had a higher ratio of patients persisted virus after oseltamivir treatment than patients >15 years (50% and 11.8%, respectively, p=0.038), and a significant higher body temperature during oseltamivir treatment, compared to patients < or =15 years treated for oseltamivir-sensitive virus infection. CONCLUSION The clinical effectiveness of oseltamivir for the A(H1N1) virus was reduced in the 2008-2009 season compared with the previous season, especially in children, probably due to the H274Y mutation. Oseltamivir seems to be not recommended for children and patients with high-risk underlying diseases infected with H274Y mutated A(H1N1) virus.

Increased symptom severity but unchanged neuraminidase inhibitor effectiveness for A(H1N1)pdm09 in the 2010–2011 season: comparison with the previous season and with seasonal A(H3N2) and B

Background  No studies of the clinical symptoms before starting therapy or of the effectiveness of neuraminidase inhibitors (NAIs) have been carried out of the 2009–2010 and 2010–2011 seasons that compare A(H1N1)pdm09 or the three circulating types of influenza virus.

2002/2003年のインフルエンザ流行状況とA, B型の複数回感染例の検討

A total of 2,320 cases of influenza A (1,517 cases) and B (803 cases) in the 2002-2003 influenza season were analyzed. Influenza infection was confirmed by a rapid diagnosis kit, based on the immunochromatography method, at 24 clinics in 18 of the 47 prefectures of Japan. Influenza A/H3N2 was reported between November 22 and April 12 (the median at January 21), and influenza B was reported between December 24 and April 20 (the median at February 16). The mean age of type B patients (16.7 years old) was significantly younger than that of type A patients (26.7 years old) (p < 0.001). Pneumonia was more frequently a complication of type A (0.63%) than of type B (0%, p < 0.05). Although 5 type A patients needed hospitalization, neither hospitalization nor death was associated with type B. Of the 2,293 cases, 27 (1.2%) were infected with both influenza of A and B. The age of these 27 patients ranged from 2 to 51 years (mean of 11.2 years), but 20 of the 27 patients were 9 years of age or under. Type B followed type A in 25 patients. The median date of these 25 type A patients was January 22, similar to that of all cases of type A, January 21. However, the median date of type B infection was March 3, 15 days later than that of all patients with type B, February 16. The mean age of the 27 cases was significantly younger than that of all cases of type A (p < 0.001) and type B (p < 0.05). In epidemics consisting of multiple types of influenza viruses, patients may be infected by more than one virus. This is especially true for children.

Mycobacterium chelonae subsp. abscessusによる肺感染症の2症例

Two cases of lung infection due to Mycobacterium chelonae subsp. abscessus are reported. Case 1, a 50-year-old female, was a secondary infection-type, and case 2, a 53-year-old female, was a primary infection-type. The 16 cases reported, between the ages of 29 and 76 years, there were 6 males and 10 females. The roentgenographic examinations, revealed that the ratio of the primary and secondary infection-type was 3:1. Effective agents for this organism has not been yet confirmed. In the present study, we treated two patients with AMK and IPM/CS, and obtained negative conversion of the sputum culture as well as improvement of roentgenographic features.