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Large scale investigation of the clinical effectiveness of neuraminidase inhibitors for circulating influenza viruses are important along with the surveillance of virus susceptibility in vitro.The duration of fever and other influenza symptoms as markers of the clinical effectiveness of laninamivir octanoate hydrate (laninamivir) were investigated in the Japanese 2017/18 and 2018/19 influenza seasons and compared with the results of the previous six seasons.Influenza A(H1N1)pdm09, A(H3N2), and B were found in 14, 45, and 52 patients in the 2017/18 season and in 22, 62, and 0 in the 2018/19 season, respectively. The median duration of fever for B was significantly longer than for A(H1N1)pdm09 and A(H3N2) in the 2017/18 season (p = 0.0461) and for A(H3N2) than for A(H1N1)pdm09 in the 2018/19 season (p = 0.0290). However, the differences were subtle in both seasons for other symptoms, with no significant differences in their median duration in comparison of the circulating types/subtypes. Over the eight seasons with the previous six seasons added, the median durations of fever were consistently longer for B than for A, but the relation between the A subtypes was inconsistent. The median durations of fever were comparable over the eight seasons for the virus types/subtypes, as were the median durations of other symptoms. The percentage of febrile patients decreased in a similar pattern over the eight seasons for each type/subtype.The results confirmed that laninamivir has continued to be clinically effective against all types/subtypes of influenza viruses, with no safety issues.

Although the virological and clinical efficacies of baloxavir for influenza and the post-treatment emergence of variant viruses have been reported in clinical trials, its efficacies have not been fully investigated in clinical settings. This prospective, observational investigator-initiated study was conducted during the 2019–2020 Japanese influenza season. In outpatients receiving baloxavir or oseltamivir, nasopharyngeal samples were obtained on day 1 before treatment and on the scheduled days 5 and 10 after treatment. RT-PCR and sequencing were performed to detect polymerase acidic protein (PA) E23X/I38X and neuraminidase (NA) H275Y variants in clinical and cultivated samples. Fever and illness-related symptoms were recorded using self-reporting diaries. Overall, 116 outpatients, 76 treated with baloxavir (34 under 12 years) and 40 with oseltamivir (32 under 12 years), were eligible. Of these, 91 were infected with A (H1N1)pdm09 (78.4%), of which 58 received baloxavir and 33 received oseltamivir. PA variants were detected in clinical (1.7%, 1/58; 3.8%, 1/26 for children under 12 years) and isolated (3.4%, 2/58; 3.8%, 1/26 for children under 12 years) samples obtained on day 5 after baloxavir treatment, but not on day 10. The isolation frequencies of A (H1N1)pdm09 on days 5 and 10 after baloxavir treatment were 5.2% (3/58) and 0.0% (0/58), respectively. Of the three viruses isolated on day 5, two (66.7%, 2/3) were PA I38 T/F variants with reduced baloxavir susceptibility. The isolation frequencies of A (H1N1)pdm09 on days 5 and 10 after oseltamivir treatment were 30.3% (10/33) and 6.1% (2/33), respectively. Only the two viruses isolated on day 10 were NA H275Y variants. The median duration of fever in baloxavir and oseltamivir recipients was 22.3 and 27.5 h, respectively. No patients with PA or NA variants showed prolonged durations of fever. Baloxavir was virologically effective for influenza in the clinical setting of the 2019–2020 Japanese season. Variant emergence after baloxavir treatment was limited to the early post-treatment stage.

Four pediatric clinics in Fukuoka, Japan, collected 822 cases of nasopharyngeal specimens from patients with influenza-like symptoms from 1 October 2002 to 31 March 2003. Age distribution of these cases was 6 months to 15 years old and mean age was 5.98 years old. Two hundred seventy-eight cases were positive for influenza type A(H3N2) and 176 cases for type B. When compared with virus culture, the sensitivity of the rapid detection kits for type A(H3N2) was 89.4% by nasal swab and 78.8% by throat swab, while type B testing revealed 75.7% positive by nasal swab and 78.3% by throat swab. Comparison of sensitivity of rapid detection kits to virus culture from the onset of influenza-like illness showed testing at 6 h from onset yielded the highest sensitivity (89.3%) in A(H3N2) (p

Antigenicity of all the A(H3) viruses which we isolated from specimens collected in Sendai and Fukuoka, Japan in 2002–2003 influenza season was examined by hemagglutination inhibition test (HI) using the ferret antiserum against A/Panama/2007/99 (H3N2), the vaccine strain for the past three influenza seasons, provided by WHO Influenza Collaborating Center, Japan. All the viruses were isolated in MDCK cell system. From the beginning of the epidemic, we found that many isolated virus strains reacted with the standard antiserum more than 4- to 16-fold less than its homologous titer, in both cities. The number of isolation of such antigenic drifted viruses increased and dominated the isolates in this season. We show here the chronological appearance of such variants in this season. Furthermore, we performed genetic analyses on the HA genes of the isolates along with those of previous two consecutive seasons. Thus it was revealed that the isolates of this season make a clear cluster different from the cluster in the previous seasons, and the variants of 2002–2003 season make a different cluster from those of previous two seasons. Moreover, no difference was found in clusters which could explain the difference between these variants and nonvariants, and among variants isolated in four cities.

A series of studies were performed to investigate the ability of rapid antigen-detection kits in diagnosis of influenza. Clinical specimens were collected from a total of more than 3000 cases of influenza-like illness who visited out-patient clinics in Sendai and Fukuoka, Japan, during the 2001–2002 and 2002–2003 influenza seasons. Each clinical specimen was examined with a kit and virus isolation, and results were analyzed retrospectively by several points of interest: sensitivity of the kits based on the virus isolation and the sensitivity by type and subtype of influenza, kinds of specimens, the time course of influenza, and variation of sources of the specimens. Thus, the sensitivities of a kit were 83%, 52% and 58% in general for influenza A(H3N2), A(H1N1), and B, respectively, and those of another kit were 76%, 71%, and 62%, respectively, in 2001–2002 influenza season. The sensitivity using nasal swabs was better than that using throat swab, though only 5% up. Specimens tended to be less sensitive when collected shortly after the onset of illness, and the sensitivity seemed quite varied (17–92%) by source of specimens: staff who collect the specimens, and/or by population of the patients.