Local spread of influenza A (H1N1) viruses without a mutation for the maximum duration of an epidemic season in Japan.

Close observation of the local transmission of influenza A(H1N1) viruses enabled an estimate of the length of time the virus was transmitted without a mutation. Of 4,448 isolates from 11 consecutive years, 237 isolates could be categorized into 57 strain groups with identical hemagglutinin genes, which were monitored for the entire duration of an epidemic season. In addition, 35 isolates with identical sequences were identified at the study site and in other countries within 147 days. Consequently, it can be postulated that once an influenza virus enters a temperate region, the strain rarely mutates before the end of the season.

Growth capability of epidemic influenza viruses in Japan since the 2009 H1N1 pandemic.

The correlation of viral growth capability (n = 156) with the viral load in nasopharyngeal swabs (n = 76) was assessed. Epidemic influenza A/H1N1, A/H3N2, and B viruses showed a wide range of growth capability (104-1011 copies/mL) in Madin-Darby canine kidney cells. The growth was correlated with the nasopharyngeal viral load (r = 0.53). Six selected strains showed growth-dependent cell death (r = 0.96) in a growth kinetics assay. Epidemic influenza viruses exhibit a wide range of growth capability. Growth capability should be considered one of the key factors in disease prognosis.

Reduced replication capacity of influenza A(H1N1)pdm09 virus during the 2010-2011 winter season in Tottori, Japan.

A novel swine-origin influenza A(H1N1)pdm09 virus has been circulating in humans since March-April, 2009. The 2009-2010 epidemic involved predominantly a single subtype of A(H1N1)pdm09 (at 96%, 46/48) in the sentinel sites of this study. However, A(H1N1)pdm09 started to circulate together with other type/subtype (49%, 33/68) at the first peak in the next epidemic season in 2010-2011: A(H1N1)pdm09/A(H3N2) (9%, 6/68), A(H1N1)pdm09/B (35%, 24/68), and A(H1N1)pdm09/A(H3N2)/B (4%, 3/68). Single infection of A(H1N1)pdm09 became a rare event (8%, 5/65) at the second peak of the same season in 2010-2011 compared with that at the first peak (50%, 34/68). Concurrently with this decline, single infections of others, A(H3N2) or B, became evident (6%, 4/65; 14%, 9/65, respectively). Triple infections were more common (29%, 19/65) at the second peak than at the first peak (4%). The A(H1N1)pdm09 detected in 2010-2011 produced less virus upon 72 hr of incubation in vitro after the inoculations at 10(4) and 3,300 copies/ml (2.3 × 10(9) and 2.3 × 10(9) copies/ml on average) than that in 2009-2010 (3.7 × 10(9) and 1.3 × 10(10) copies/ml on average; P<0.05 by ANOVA test), respectively. As described above, the replication capacity of A(H1N1)pdm09 seems to have deteriorated in the 2010-2011 season presumably due to substantial herd immunity and allowed the existence of other type/subtype. These results suggest that assessment of replication capacity is indispensable for analysis of influenza epidemics.

[Successful management of sigmoidectomy with sildenafil citrate in a patient with acute exacerbation of chronic thromboembolic pulmonary hypertension].

An 84-year-old woman with pulmonary hypertension (PH) secondary to chronic pulmonary thromboembolism suffered from continuous warfarin dependent bleeding from sigmoid colon cancer. Sigmoidectomy was scheduled to control continuous bleeding. Six hours after discontinuation of anticoagulant therapy for elective sigmoidectomy, the patient showed hypoxia, pulmonary thromboembolism and pulmonary hypertension with right ventricular systolic pressure (RVSP) of 81 mmHg. The operation was postponed and heparin was infused. Since two-day heparinization therapy did not improve PH, oral administration of sildenafil citrate 60 mg daily was initiated. Seven days after initiation of sildenafil administration, RVSP decreased to 49 mmHg without improvement of hypoxia. Sigmoidectomy was performed under general anesthesia. The patient showed severe hypotension managed with noradrenaline and dopamine infusion during and after surgery, resulting from interaction between sildenafil and vasodilators. The patient was discharged 36 days after the operation without complications.

Prevalence and clinical characteristics of children with medical complexity in Tottori Prefecture, Japan: A population-based longitudinal study.

OBJECTIVES: To investigate the prevalence and background of children with medical complexity (CMC) and its secular trend in Japan. METHODS: CMC were defined as patients under the age of 20 years requiring medical care and devices. The patients were enrolled using the national health insurance claims data of three hospitals and two rehabilitation centers in Tottori Prefecture. The study period was divided into three periods: Period 1, 2007-2010; Period 2, 2011-2014; and Period 3, 2015-2018. RESULTS: A total of 378 CMC were enrolled. The prevalence of CMC was 1.88 per 1000 population among subjects aged <20 years in 2018, and it increased by approximately 1.9 times during the study period. The number of CMC who presented with severe motor and intellectual disabilities did not change from Period 1 to Period 3. Meanwhile, the number of CMC who had relatively preserved motor and intellectual abilities increased from 58 to 98. The proportion of CMC who required respiratory management and oxygen therapy increased by 1.3 and 1.8 times, respectively. By contrast, the proportion of CMC who need tube feeding decreased significantly between periods 1 and 3 (P < 0.05). CONCLUSIONS: The prevalence of CMC increased almost twice during the 12-year study period; however, the increase in the number of patients with relatively preserved motor and intellectual abilities was pronounced. This study showed that the need for medical care and devices differed based on the underlying disorders and severity of CMC; therefore, individualized medical, welfare, and administrative services and education about the various types of CMC must be provided.

Frequent Isolations of Influenza A Viruses (H1N1)pdm09 with Identical Hemagglutinin Sequences for More Than Three Months in Japan.

BACKGROUND: Although it has been suggested that antigenic drift does not occur in a single epidemic season in temperate countries, there is not enough evidence on the circulation period of influenza virus with identical nucleotide sequences. Therefore, strains of influenza virus were isolated sequentially during five consecutive epidemic seasons in Japan and their nucleotide sequences were determined. METHODS: Nasal swabs or aspirated nasal discharges were collected from influenza A virus antigen-positive individuals living in Tottori Prefecture, Japan for five consecutive winters starting in 2009-2010, and subjected to viral isolation, determination of hemagglutinin nucleotide sequence and phylogenic analyses. The nucleotide sequences were compared with each other and also with those of foreign strains in the International Nucleotide Sequence Database. RESULTS: Totally 288 A(H1N1)pdm09 strains were tested and those composed 38 clusters with identical ones displaying 100% nucleotide homology. One strain showed sequential infections more than three months without any detectable mutation, and a maximum interval of two detection timings of strains was 94 days. This implies that influenza viruses mutate rarely in an epidemic season in Japan if they can be hypothesized, mutation frequency of influenza viruses being mostly the same among strains. Among these identical strains, two strains were not only identical to other Japanese isolates, but also to those isolated in Mongolia and Thailand in the same epidemic season. CONCLUSION: These results suggest that genetic drift has occurred infrequently in Japan as shown in some other countries. The drifted strains may have generated somewhere else and entered into Japan. These results support the proposed 'sink-source' model of viral ecology in which new lineages are seeded from a persistent influenza reservoir in tropical countries to 'sink' populations in temperate regions including Japan.

Early predictors of status epilepticus-associated mortality and morbidity in children.

BACKGROUND: Early predictors of status epilepticus (SE)-associated mortality and morbidity have not been systematically studied in children, considerably impeding the identification of patients at risk. OBJECTIVES: To determine reliable early predictors of SE-associated mortality and morbidity and identify the etiology of SE-associated sequelae in Japanese children. METHODS: We conducted a prospective multicenter study of clinical findings and initial laboratory data acquired at SE onset, and assessed outcomes at the last follow-up examination. In-hospital death during the acute period and neurological sequelae were classified as poor outcomes. RESULTS: Of the 201 children who experienced their first SE episode, 16 exhibited poor outcome that was most commonly associated with acute encephalopathy. Univariate analysis revealed that the following were associated with poor outcomes: young age (⩽24 months); seizure duration >90 min; seizure intractability (failure of the second anticonvulsive drug); biphasic seizures; abnormal blood glucose levels (<61 or >250 mg/dL); serum aspartate aminotransferase (AST) ⩾56 U/L; and C-reactive protein (CRP) levels >2.00 mg/dL. Multivariate analysis revealed that young age, seizure intractability, abnormal blood glucose levels, and elevated AST and CRP levels were statistically significant. CONCLUSIONS: Young age and seizure intractability were highly predictive of poor outcomes in pediatric SE. Moreover, abnormal blood glucose levels and elevated AST and CRP levels were predictors that might be closely associated with the etiology, especially acute encephalopathy and severe bacterial infection (sepsis and meningitis) in Japanese children.