Efficacy and safety of ketamine for pediatric and adolescent super-refractory status epilepticus and the effect of cerebral inflammatory conditions.

OBJECTIVE: To investigate the short-term benefits and adverse effects of ketamine in the treatment of pediatric and adolescent super-refractory status epilepticus (SRSE), with a focus on the inflammatory etiology. METHODS: This retrospective observational cohort study included a consecutive series of 18 pediatric to adolescent patients with SRSE admitted between 2008 and 2023 and treated with ketamine. Seizure frequency per hour before and after ketamine administration and response rate were calculated. Neurological decline, catecholamine administration, and adverse effects were also assessed. The patients were divided into inflammatory and non-inflammatory etiology groups. RESULTS: The median age at SRSE onset was 1 year 5 months (range: 11 days-24 years), and 78% of the patients were male individuals. The median duration of treatment was 7.5 days (interquartile range: 2.8-15.5 days). Fifteen (83%) patients achieved >50% seizure reduction. The median seizure frequency before and after ketamine treatment was 5.9 and 0.9, respectively, showing a significant reduction in seizure frequency (p < 0.0001). Ten patients had inflammatory etiologies including bacterial meningitis (n = 2), viral encephalitis (n = 3), and febrile infection related epilepsy syndrome (n = 5). The inflammatory etiology group required a longer treatment duration (p = 0.0453) and showed lower seizure reduction (p = 0.0264), lower response rate (p = 0.0044), and higher neurological decline (p = 0.0003) than the non-inflammatory etiology group. Three (17%) patients experienced transient adverse events requiring intervention within 24 h of initiating ketamine administration. CONCLUSIONS: Ketamine administration was associated with fewer serious adverse events and a reduced seizure frequency. Additionally, inflammatory conditions may weaken the efficacy of ketamine in patients with SRSE.

Phase I Study to Assess the Safety and Immunogenicity of an Intradermal COVID-19 DNA Vaccine Administered Using a Pyro-Drive Jet Injector in Healthy Adults.

We conducted a nonrandomized, open-label phase I study to assess the safety and immunogenicity of an intradermal coronavirus disease 2019 (COVID-19) DNA vaccine (AG0302-COVID-19) administered using a pyro-drive jet injector at Osaka University Hospital between Yanagida November 2020 and December 2021. Twenty healthy volunteers, male or female, were enrolled in the low-dose (0.2 mg) or high-dose (0.4 mg) groups and administered AG0302-COVID19 twice at a 2-week interval. There were no adverse events that led to discontinuation of the study drug vaccination schedule. A serious adverse event (disc protrusion) was reported in one patient in the high-dose group, but the individual recovered, and the adverse event was not causally related to the study drug. In the analysis of the humoral immune response, the geometric mean titer (GMT) of serum anti-SARS-CoV-2 spike glycoprotein-specific antibody was low in both the low-dose and high-dose groups (246.2 (95% CI 176.2 to 344.1, 348.2 (95% CI 181.3 to 668.9)) at the 8 weeks after first vaccination. Regarding the analysis of the cellular immune, the number of IFN-γ-producing cells responsive to the SARS-CoV-2 spike glycoprotein increased with individual differences after the first dose and was sustained for several months. Overall, no notable safety issues were observed with the intradermal inoculations of AG0302-COVID19. Regarding immunogenicity, a cellular immune response was observed in some subjects after AG0302-COVID19 intradermal inoculation, but no significant antibody production was observed.

Characteristics and incidence of vaccine adverse events after Bacille Calmette-Guérin vaccination: A national surveillance study in Japan from 2013 to 2017.

BACKGROUND: Japan amended the recommended age for the Bacille Calmette-Guérin (BCG) vaccination to less than 6 months after 2005, but subsequently amended the recommended age to 5-8 months (latest amendment, <1 year) in April 2013 due to the increasing incidence of BCG-associated osteitis/osteomyelitis since 2005. METHODS: We collected data on BCG-associated vaccine adverse events (VAEs) in the population aged <1 year between April 2013 and March 2017. The incidence of BCG-associated VAE was analyzed using census and vaccine coverage data from the government website. We compared the incidence of VAEs in patients vaccinated at less than 6 months with those vaccinated at 6 months or older. RESULTS: Among the 581 BCG-associated VAEs recorded during the study period, 354 (61%) were male, and the average age at vaccination was 5.7 months. The incidence of VAEs per million population aged <1 year at vaccination was highest for suppurative lymphadenitis (63.7), followed by skin lesions (38.4), and BCG-associated osteitis/osteomyelitis (3.1). Disseminated BCG and anaphylaxis were rare (1.1 and 1.6%, respectively). The incidence of VAEs in the population vaccinated at <6 months of age was higher for BCG-associated osteitis/osteomyelitis (3.8) and disseminated BCG (1.3) than in the population vaccinated at ≥6 months. CONCLUSIONS: The population vaccinated at <6 months of age was more likely to develop BCG-associated osteitis/osteomyelitis than the population vaccinated at ≥6 months of age, indicating that the change in the recommended vaccination age in 2013 might have contributed to the subsequent decrease in the incidence of BCG-associated osteitis/osteomyelitis.

Epidemiology of Congenital Rubella Syndrome Related to the 2012-2013 Rubella Epidemic in Japan.

This study assessed the epidemiological characteristics of 45 congenital rubella syndrome cases in Japan following the 2012-2013 rubella epidemic. Rubella still poses significant health burdens and the uptake of rubella-containing vaccines among women of childbearing age should be improved.

Impact of Refutational Two-Sided Messages on Attitudes Toward Novel Vaccines Against Emerging Infectious Diseases During the COVID-19 Pandemic.

Two-sided messages that include two perspectives (i.e., risks and benefits) are more effective than one-sided messages that convey only one perspective (usually only the benefits). Refutational two-sided messages are effective for communicating risks regarding vaccines. To examine the effectiveness of refutational two-sided messages in risk communication regarding novel vaccines against emerging infectious diseases, we conducted the randomized controlled study based on a 3 × 3 × 2 mixed design (Intervention 1: vaccines against subcutaneous influenza, "novel severe infectious disease," or intranasal influenza; intervention 2: one-sided, non-refutational two-sided, or refutational two-sided messages; two questionnaires) using a Japanese online panel. Participants completed questionnaires before and after receiving an attack message (negative information). We evaluated the impact of attack messages on the willingness to be vaccinated, and the anticipated regret of inaction (ARI). Among 1,184 participants, there was a significant difference in the willingness to be vaccinated among the message groups (p < 0.01). After receiving the attack message, willingness to be vaccinated decreased in the one-sided message group and increased in the non-refutational two-sided and refutational two-sided message groups. Additionally, ARI in the refutational two-sided message groups was significantly higher than in the one-sided groups (p = 0.03). In conclusion, two-sided messages are more effective than one-sided messages in terms of willingness to be vaccinated. Furthermore, the high ARI in the refutational two-sided message group indicated that refutational two-sided messages were more effective than one-sided messages for communicating the risks of vaccines, especially those against emerging infectious diseases.

Effects of message order and active participation on vaccine risk communication.

BACKGROUND: "Message order" and "active participation" could be effective as risk communication methods. "Anticipated regret" (AR) has also been recognized as affecting risk perception and vaccine uptake in vaccination risk communication. We aimed to evaluate the effects of message order and active participation and the interactions between these two interventions on AR for vaccination. METHODS: We conducted a 2 (message order: positive-negative or negative-positive) × 2 (message calendar: with or without planning) factorial design study among 81 study participants. The effects of message order and active participation of mothers, using a message calendar, were evaluated on mothers' decision-making regarding vaccination with Haemophilus influenzae type b vaccine and pneumococcal conjugate vaccine for their children. Participants completed questionnaires to evaluate the AR of infection if unvaccinated (anticipated regret of inaction) and of side effects if vaccinated (anticipated regret of action, ARA) twice: immediately after interventions and 1 month later. RESULTS: An interaction between message order and active participation was significant with regard to anticipated regret of inaction immediately after interventions (P = 0.01), but this effect disappeared 1 month after interventions. The message order showed no main effect with regard to ARA. However, the main effect of active participation was marginally significant with regard to ARA 1 month after intervention (P = 0.09); AR over vaccine side effects was lower when vaccination was planned than in the condition without planning. CONCLUSIONS: The effect of message order was hardly detectable in a clinical setting. However, active participation induced by planning may affect AR. Further studies are needed to evaluate the effect of active participation in decision-making for vaccination.

The characteristics and clinical course of patients with COVID-19 who received invasive mechanical ventilation in Osaka, Japan.

OBJECTIVE: To describe the detailed clinical course of patients with coronavirus disease 2019 (COVID-19) who received invasive mechanical ventilation. METHODS: We conducted a case series of patients with COVID-19 who received invasive mechanical ventilation in Osaka, Japan, between January 29 and May 28, 2020. We describe the patient characteristics and clinical course from onset. Additionally, we fitted logistic regression models to investigate the associations between patient characteristics and the 30-day mortality rate. RESULTS: A total of 125 patients who received invasive mechanical ventilation (median age [interquartile range], 68 [57-73] years; male, 77.6%) were enrolled. Overall, the 30-day mortality was 24.0%, and the median (interquartile range) length of ICU stay and length of invasive mechanical ventilation use were 16 (12-29) days and 13 (9-26) days, respectively. From clinical onset, 121 patients (96.8%) were intubated within 14 days. In multivariable logistic regression analysis, age of 65 years or older (odds ratio, 3.56; 95% confidence interval, 1.21-10.49; P = 0.02) and male sex (odds ratio, 3.75; 95% confidence interval, 1.00-11.24, P = 0.04) were significantly associated with a higher 30-day mortality rate. CONCLUSIONS: In this case series of patients with COVID-19 who received invasive mechanical ventilation in Japan, the 30-day mortality rate was 24.0%, and age 65 years or older and male sex were associated with higher 30-day mortality rate.

Rubella outbreak among workers in three small- and medium-size business establishments associated with imported genotype 1E rubella virus-Shizuoka, Japan, 2015.

On 12 February 2015, a local health department (LHD) in Shizuoka prefecture identified two reported rubella cases in its jurisdiction as employees of the same company. As other employees at the company resided both inside and outside of the health department's jurisdiction, it began collaborating with two additional LHDs and the National Institute of Infectious Diseases to investigate and respond to the outbreak, which subsequently identified cases in two additional companies. We obtained epidemiological, clinical, and outbreak response information from the national epidemiological surveillance of infectious disease system's database, the local health departments, and the associated companies. One specimen for genetic sequencing was collected from each of the three companies. The outbreak included a total of twenty-five cases, with seventeen confirmed and eight probable cases from three companies. Among them, 24 (96%) were male, 22 (88%) were employees of one company (Company X), and none had rubella vaccination history. The median age was 45 years (interquartile range: 40-51). Epidemiological information did not reveal the source of infection nor transmission route. All rubella viruses sequenced from the three specimens were classified into genotype 1E. The nucleotide sequences in the 739 bp-window region were completely identical in two specimens, with only one nucleotide difference in the third specimen. According to phylogenetic analysis, these strains were closely related to the Southeast and East Asian lineage. This rubella outbreak at three companies, ranging in size from small- to medium-size, in Japan occurred among unvaccinated employees aged at least 30 years, most of whom were male. Virologic analyses suggest all cases were infected with the same viral strain imported from Southeast Asia. Similar to these companies, most employees at small- and medium-size businesses in Japan are males with no vaccination history for rubella, which poses a serious risk for associated cases of congenital rubella syndrome (CRS).

Epidemiology of a workplace measles outbreak dominated by modified measles cases at Kansai international airport, Japan, during august-september 2016.

OBJECTIVES: In August 2016, a measles outbreak at Kansai International Airport was the first workplace measles outbreak since Japan was verified as having achieved measles-elimination status in March 2015. We investigated this outbreak with a focus on evaluating the ability of vaccinated individuals to transmit measles virus (MV). METHODS: We considered a case of laboratory-confirmed measles with onset between August 9 and September 29, 2016, among workers of Kansai International Airport. History of vaccination status with measles-containing vaccine (MCV) was confirmed by reviewing records. The potential sources of each MV infection were assessed by interviewing each infected worker about the clinical course of their infection and their behavioral history. RESULTS: Of 30 affected ground crews identified, 16 (53%) were vaccinated with ≥ 1 dose of MCV, 2 (7%) were unvaccinated, and 12 (40%) had an unknown vaccination status. The index case, a patient with classical measles with unknown vaccination status, presumably transmitted MV to all the subsequent 29 cases. The majority of patients (23, 77%; 15 vaccinated, 8 in unknown vaccination status) were diagnosed with modified measles due to mild illness. Modified measles were characterized clinically by signs of catarrh (4/23, 17%) in a few cases, with a median incubation period of 16 (range, 11-21) days. No onward transmission from vaccinated cases was suggested. An overseas traveler who visited the airport with measles symptoms was identified as the possible primary source of this outbreak. CONCLUSIONS: The low MV transmission ability of vaccinated individuals was reaffirmed. Contact tracing of vaccinated modified measles cases can be limited to a person at high risk of infection (e.g., households, person with immunosuppression). To maintain measles-elimination status, completing two doses of MCV should be ensured, especially for international travelers and for those who are frequently exposed to these travelers, such as airport workers.

Immune thrombocytopenic purpura risk by live, inactivated and simultaneous vaccinations among Japanese adults, children and infants: a matched case-control study.

This case-control study investigated immune thrombocytopenic purpura (ITP) risk following live, inactivated, and simultaneous vaccination, with a focus on infants aged < 2 years. We matched case patients with ITP to one or two control patients with other diseases by institution, hospital visit timing, sex, and age. We calculated McNemar's pairwise odds ratios (ORs [95% confidence interval]) with 114 case-control pairs. The case group had 27 (44%) males and 22 (35%) infants, and the control group included 49 (43%) males and 42 (37%) infants. For all age groups, the McNemar's OR for ITP occurrence was 1.80 (0.54-6.84, p = 0.64) for all vaccines. Among infants, these were 1.50 (0.17-18.0, p = 0.50) for all vaccines, 2.00 (0.29-22.1, p = 0.67) for live vaccines, and 1.00 (0.01-78.5, p = 0.50) for inactivated vaccines. Sex-adjusted common ORs for simultaneous vaccination were 1.52 (0.45-5.21, p = 0.71) for all vaccines, 1.83 (0.44-7.59, p = 0.40) for inactivated vaccines only, and 1.36 (0.29-6.30, p = 0.69) for mixed live and inactivated vaccines. In infants, these were 1.95 (0.44-8.72, p = 0.38), 1.41 (0.29-6.94, p = 0.67) and 2.85 (0.43-18.9, p = 0.28), respectively. These limited data suggest no significant ITP risk following vaccinations or simultaneous vaccination in any age group, including infants.

Comparison of Haemophilus influenzae Seroprevalence in Serum Samples Collected from 0- to 5-Year-Old Japanese Children in 1980, 1995, 2010, and 2012.

Haemophilus influenzae type b (Hib) causes several invasive infections such as meningitis, septic arthritis, and pneumonia, especially in children below 5 years old. Despite the availability of Hib vaccines against Hib infection, seroepidemiological surveys of Hib infections have not yet been systematically conducted in Japan. We analyzed 1,338 serum samples, provided by the National Serum Reference Bank of the National Institute of Infectious Diseases (Tokyo, Japan), from 0- to 5-year-old children. Anti-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) antibody levels against Hib were determined using an anti-H. influenzae IgG enzyme immunoassay kit. In a total of 1,168 (87.3%) serum samples from children, anti-PRP IgG antibody levels were ≥ 0.15 µg/mL, providing natural immunity. Titers expected to provide long-term protection (≥ 1 µg/mL) were increased from 2.7% to 51.6% in children < 1 year old after the introduction of Hib vaccine (1980, 5.3%; 1995, 2.7%; 2010, 22%; 2012, 51.6%). Our data confirmed that the introduction of Hib vaccination in children below 5 years old increased the proportion of children having high anti-PRP IgG antibody levels, ensuring long-term protection against Hib.

Mycobacterium kansasii arthritis of the elbow in an immunocompetent patient with a suspected soft-tissue tumor.

Mycobacterium kansasii is one of the major non-tuberculous mycobacteria species that typically cause pulmonary diseases. M. kansasii is known to cause septic arthritis as an extrapulmonary disease in immunosuppressed patients or chronic skin disease. Herein, we present a case of M. kansasii arthritis involving the elbow of an immunocompetent patient, which was initially suspected to be a soft-tissue tumor. A 70-year-old man presented with a swollen left elbow that had progressed for 18 months with deteriorating arthralgia and limited range of motion. Magnetic resonance imaging revealed filling of the intra-articular space of the elbow and surrounding of the radial head with a soft tissue mass with mixed signal intensity. Initial incisional biopsy was performed via the lateral approach to the elbow joint, and pathological examination of the mass did not reveal any evidence of malignancy. One year after the first operation, arthroscopic surgery was performed to excise the mass following the recurrence of swelling and limited function of the elbow. Pathological examination of the resected synovium revealed epithelioid granulomas containing a multinucleated giant cell and inflammatory cell infiltration, characteristic of mycobacterial infection. M. kansasii was cultured after 2 weeks of incubation of the synovial sample. He experienced full resolution of the swelling and limited function following a combination of synovectomy and multidrug antimycobacterial treatment (rifampin 600 mg/day, clarithromycin 800 mg/day, and ethambutol 750 mg/day). This case highlights the need to consider this rare infection in the differential diagnosis of intra-articular soft tissue tumor-like lesions even in immunocompetent patients.

Bacteremia due to high-level daptomycin-resistant Corynebacterium striatum: A case report with genetic investigation.

Corynebacterium striatum, generally considered an opportunistic organism in humans, has recently been known to develop high-level daptomycin resistance (HLDR) shortly after drug exposure. To date, however, only several such clinical isolates have been described in the literature and clinical background of the resistant pathogen remains to be elucidated. Here, we report a case involving a C. striatum strain with HLDR harboring novel nucleotide mutations, together with a review of the relevant literature. To the best of our knowledge, this is the first well-investigated clinical report from Japan including a genetic investigation. Considering the rapid emergence of HLDR C. striatum in vitro experiment, there could be a number of underreporting cases. Scrupulous attention is required when administering daptomycin for the treatment of C. striatum infections, even if the organism has initially exhibited susceptibility.

Association of Adverse Drug Events with Broad-spectrum Antibiotic Use in Hospitalized Patients: A Single-center Study.

Objective The importance of antimicrobial stewardship is increasingly highlighted in this age of antimicrobial resistance. A better comprehension of adverse drug events (ADEs) can promote the appropriate use of antibiotics. We aimed to quantify the incidence of ADEs associated with broad-spectrum systemic antibiotics in a hospital setting. Methods We conducted a six-month prospective, observational study at Osaka University Hospital to describe the incidence of ADEs in patients hospitalized in general wards undergoing treatment with broad-spectrum antibiotics [carbapenems, piperacillin/tazobactam (PIPC/TAZ), and anti-methicillin-resistant Staphylococcus aureus agents]. The occurrence of ADE was defined as any cardiac, gastrointestinal, hepatobiliary, renal, neurologic, hematologic, dermatologic, or musculoskeletal manifestation after 48 hours or more of systemic antibiotic therapy. Results The 3 most frequently prescribed antibiotics were PIPC/TAZ (242 cases), meropenem (181 cases), and vancomycin (92 cases). Of 689 patients, 118 (17.1%) experienced ADEs, including gastrointestinal (6.4%), hepatobiliary (4.2%), dermatologic (2.5%), and renal (2.3%) manifestations. Patients treated with PIPC/TAZ, meropenem, doripenem, vancomycin, daptomycin, and teicoplanin developed ADEs at rates of 20.7%, 16.0%, 15.4%, 19.6%, 11.8%, and 10.9%, respectively. Conclusion Our study provides a quantitative value for the incidence of ADEs associated with broad-spectrum antibiotics in clinical practice. To optimize patient safety, clinicians need to be aware of the risks associated with antibiotic administration.

Polio vaccination coverage and seroprevalence of poliovirus antibodies after the introduction of inactivated poliovirus vaccines for routine immunization in Japan.

In Japan, the oral poliovirus vaccine (OPV) was changed to 2 types of inactivated poliovirus vaccine (IPV), the standalone conventional IPV (cIPV) and the Sabin-derived IPV combined with diphtheria-tetanus-acellular pertussis vaccine (DTaP-sIPV), for routine immunization in 2012. We evaluated polio vaccination coverage and the seroprevalence of poliovirus antibodies using data from the National Epidemiological Surveillance of Vaccine-Preventable Diseases (NESVPD) from 2011 to 2015. Several years before the introduction of IPV in 2012, OPV administration for children was refused by some parents because of concerns about the risk of vaccine-associated paralytic poliomyelitis. Consequently, in children aged <1 years who were surveyed in 2011-2012, polio vaccination coverage (45.0-48.8%) and seropositivity rates for poliovirus (type 1: 51.7-65.9%, type 2: 48.3-53.7%, and type 3: 15.0-29.3%) were decreased compared to those surveyed in 2009. However, after IPV introduction, the vaccination coverage (95.5-100%) and seropositivity rates (type 1: 93.2-96.6%, type 2: 93.1-100%, and type 3: 88.6-93.9%) increased among children aged <1 years in 2013-2015. In particular, seropositivity rates and geometric mean titers (GMTs) for poliovirus type 3 in <5-year-old children who received 4 doses of IPV (98.5% and 247.4, respectively) were significantly higher than in those who received 2 doses of OPV (72.5% and 22.9, respectively). Furthermore, in <5-year-old children who received 4 doses of either DTaP-sIPV or cIPV, the seropositivity rates and the GMTs for all 3 types of poliovirus were similarly high (96.5-100% and 170.3-368.8, respectively). Our findings from the NESVPD demonstrate that both the vaccination coverage and seropositivity rates for polio remained high in children after IPV introduction.

Nationwide survey of influenza-associated acute encephalopathy in Japanese adults.

BACKGROUND: Knowledge of adult patients with influenza-associated acute encephalopathy (IAE) is limited. We conducted a detailed survey to investigate the prevalence, clinical features, associated outcomes, and prognostic factors in adult IAE patients. METHOD: A nationwide questionnaire on IAE patients was sent to the departments of Internal Medicine, Neurology, Neurosurgery, and Emergency and Critical Care at all hospitals with ≥200 beds in Japan. RESULTS: 118 patients were diagnosed with IAE during the 2013/14 to 2015/16 influenza seasons, and the estimated annual incidence of IAE in Japanese adults was 0.98/1000,000 population. 44 patients were subsequently enrolled in the detailed study. 93% of patients exhibited disturbance of consciousness. Convulsions and delirious behavior were present in 26% and 40% of patients, respectively. 65% of patients received pulse corticosteroid therapy with methylprednisolone and 21% of patients received intravenous gamma-globulin therapy. 63% of patients achieved a good recovery, but 7% died. Multiple logistic regression analysis revealed that plasma glucose level demonstrated a statistically significant association with poor outcome. CONCLUSION: This nationwide survey provided data for the annual incidence and clinical features of IAE in Japanese adults. Hyperglycemia was indicated as an independent predictor of poor prognosis in IAE patients and reflected systemic hypercytokinemia in IAE pathogenesis.

Antibiotic-associated adverse drug events at a Japanese academic hospital.

INTRODUCTION: To promote antimicrobial stewardship activity, an understanding of the incidence of antibiotic-associated adverse drug events (ADEs) is essential. In this study, we aimed to describe the occurrence of antibiotic-associated ADEs at our hospital. METHODS: We retrospectively searched the ADE registration system in Osaka University Hospital between 2010 and 2017. Registrations of ADEs were dependent on the patients' drug history and clinical course after hospitalization. We classified the data according to types of ADEs (gastrointestinal, hepatobiliary, renal, cardiac, respiratory, hematologic, neurologic, dermatologic, and musculoskeletal) and antibiotic class. RESULTS: During the study period, we found 707 cases of antibiotic-associated ADEs, accounting for 22.3% of all the cases. Beta-lactam antibiotics constitute more than half of the cases (51.3%). The most common ADE was dermatologic abnormalities (53.4%), followed by liver dysfunction (9.7%) and gastrointestinal symptoms (8.9%). Among all antibiotics, oral third-generation cephalosporins were frequently reported as offending drugs (107 cases), accounting for 29.5% of beta-lactam ADEs and 46.3% of cephem ADEs. CONCLUSION: Antibiotic-associated ADEs covered approximately 20% of all the ADEs at our hospital. We believe that the data would be helpful in ensuring patient safety by promoting antimicrobial stewardship in hospitals.

Respiratory Syncytial Virus Surveillance System in Japan: Assessment of Recent Trends, 2008-2015.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract illness in infants and young children. In Japan, surveillance for RSV infection started in 2003 based on approximately 3,000 pediatric sentinel sites. In recent years, RSV notifications have increased, but the interpretation of trends has been challenging due to a suspected increase in testing frequency and the expansion of the insurance coverage for RSV testing to include certain outpatients in late 2011. Therefore, we evaluated RSV surveillance data during 2008-2015, considering the number of sites that reported at least one RSV case during a surveillance year and restricting to sites that had continuous reporting status since 2008. While annual RSV notifications had increased, the number of sites reporting also increased. And the same magnitude of increase was not observed when the number of cases reported was restricted to the 1,372 sites that had continuous reporting status since 2008. Additionally, in the year following the insurance expansion, RSV notifications increased more remarkably for clinics than for hospitals. These results suggested that some of the recent increases in notifications might be due to an increase in testing frequency.