Genetic Comparison of Human Parainfluenza Virus Type 3 Detected in Respiratory Samples from Patients with Encephalopathy and Airway Inflammation in Aichi Prefecture, Japan.

Human parainfluenza virus type 3 (HPIV-3, human respirovirus 3) is the second most frequently detected virus in lower respiratory tract infections in children after human respiratory syncytial virus (HRSV). HPIV-3, similar to related respiratory viruses such as HRSV and influenza virus, may cause encephalopathy; however, the relevance of HPIV-3 as a pathogenic factor in encephalopathy is unknown. We attempted to detect HPIV-1, HPIV-2, HPIV-3, HPIV-4, HRSV, and human metapneumovirus (HMPV) in 136 patients with encephalitis/encephalopathy or suspected encephalitis/encephalopathy during a 6-year period from 2014 to 2019. HPIV-3 was detected in 6 patients, followed by HRSV in 3 patients. The HPIV-3 strains detected were closely related to those detected in a patient with respiratory disease during the same period. Although HPIV-3 is less widely recognized than HRSV as a triggering virus of encephalopathy, our results suggest that HPIV-3 is as important as HRSV. Surveillance of the causative viruses of encephalopathy, including HPIV-3, would help clarify the causes of encephalopathy in Japan, as the cause is currently reported in less than half of cases in Japan.

Assessing Definitions and Incentives Adopted for Innovation for Pharmaceutical Products in Five High-Income Countries: A Systematic Literature Review.

BACKGROUND: The concept of health care innovation varies across organizations and countries. Harmonizing the definitions of innovation can augment the discovery of new therapies, minimize costs, and streamline drug development and approval processes. A systematic literature review (SLR) was conducted to gather insights surrounding different elements of innovation in the USA, the UK, France, Germany, and Japan. The SLR identified studies that have defined innovation and captured the types of incentives provided to promote innovation. METHODS: The MEDLINE, Embase, and EconLit databases were searched via the OVID SP platform on October 22, 2020. A secondary desk search literature review was performed to identify additional information of interest in regional languages: French, German, and Japanese. All the relevant literature in English was screened using the Linguamatics natural language processing (NLP) tool, except for articles from EconLit, which were screened manually using structured search strategies. Articles that describe a definition of innovation or refer to a definition of innovation published were included. All full-text articles were reviewed manually, and two reviewers independently screened the full texts for eligibility. RESULTS: After screening, 90 articles were considered to meet the SLR objectives. The most common dimension of innovation identified was therapeutic benefit as a measure of innovation, followed by newness and novelty aspects of innovations. Incentives around exclusivities were found to be the most prevalent in the data set, followed by rewards and premiums. Among the different therapy areas, the largest number of innovations was targeted at oncology. CONCLUSIONS: This SLR highlights the lack of a unified definition of innovation among regulatory authorities and health technology assessment bodies in five countries, and variation in the types of incentives associated with innovation. The targeted countries cover different dimensions of definition and incentives of innovation at varying levels, with a few focused on specific therapy areas. Harmonization and consensus for innovation would be needed across countries because drug development is a global undertaking. This SLR envisages a more holistic approach to evaluation, wherein the value provided to patients and health systems is accounted for. The results of this SLR will help to promote broader discussion among different stakeholders and decision makers across countries to identify gaps in policies and develop sustainable strategies to promote innovation for pharmaceutical products.

Cost-effectiveness analysis for PCV13 in adults 60 years and over with underlying medical conditions which put them at an elevated risk of pneumococcal disease in Japan.

Background: The objective of this study was to conduct a cost-effectiveness analysis of PCV13 vs. PPV23 and no vaccination and PPV23 vs. no vaccination in adults aged ≥ 60 years with underlying medical conditions which put them at an elevated risk of pneumococcal disease in a Japanese healthcare setting.Research design and methods: A natural history model was developed with a life-long time horizon and 1-year cycle length, with microsimulation as a modeling technique. The expected costs from a public payer's and societal perspective, quality-adjusted life-years (QALYs), and prevented cases and deaths caused by IPD (invasive pneumococcal disease) and NBP (non-bacteremic pneumococcal pneumonia) were estimated.Results: In the base-case scenario, the cost per QALY gained from a public payer's perspective for PCV13 vs, PPV23 and no vaccination were 500,255JPY and 1,139,438JPY, respectively, The cost per QALY gained for PPV23 vs no vaccination was 1,687,057JPY. Over the life-long time horizon for 1 million patients, when compared to PPV23, PCV13 resulted in 65 fewer IPD cases, 2,894 fewer NBP cases, and 384 fewer deaths caused by pneumococcal disease.Conclusions: In adults aged 60 years and over with underlying medical conditions, PCV13 was shown to be a more cost-effective alternative to PPV23.

Case-based surveillance enhanced with measles virus detection/genotyping is essential to maintain measles elimination in Aichi Prefecture, Japan.

BACKGROUND: Japan was verified as having achieved measles elimination by the Measles Regional Verification Commission in the Western Pacific Region in March 2015. Verification of measles elimination implies the absence of continuous endemic transmission. After the last epidemic in 2007 with an estimated 18,000 cases, Japan introduced nationwide case-based measles surveillance in January 2008. Laboratory diagnosis for all suspected measles cases is essentially required by law, and virus detection tests are mostly performed by municipal public health institutes. Despite relatively high vaccination coverage and vigorous response to every case by the local health center staff, outbreak of measles is repeatedly observed in Aichi Prefecture, Japan. METHODS: Measles virus N and H gene detection by nested double RT-PCR was performed with all specimens collected from suspected cases and transferred to our institute. Genotyping and further molecular epidemiological analyses were performed with the direct nucleotide sequence data of appropriate PCR products. RESULTS: Between 2010 and 2014, specimens from 389 patients suspected for measles were tested in our institute. Genotypes D9, D8, H1 and B3 were detected. Further molecular epidemiological analyses were helpful to establish links between patients, and sometimes useful to discriminate one outbreak from another. All virus-positive cases, including 49 cases involved in three outbreaks without any obvious epidemiological link with importation, were considered as import-related based on the nucleotide sequence information. Chain of transmission in the latest outbreak in 2014 terminated after the third generations, much earlier than the 2010-11 outbreak (6th generations). CONCLUSION: Since 2010, almost all measles cases reported in Aichi Prefecture are either import or import-related, based primarily on genotypes and nucleotide sequences of measles virus detected. In addition, genotyping and molecular epidemiological analyses are indispensable to prove the interruption of endemic transmission when the importations of measles are repeatedly observed.

Molecular detection and nucleotide sequence analysis of a new Aichi virus closely related to canine kobuvirus in sewage samples.

Between 2001 and 2005, 207 raw sewage samples were collected at the inflow of a sewage treatment plant in Aichi Prefecture, Japan. Of the 207 sewage samples, 137 (66.2 %) were found to be positive for amplification of Aichi virus (AiV) nucleotide using reverse transcription (RT)-PCR with 10 forward and 10 reverse primers in the 3D region corresponding to the nucleotide sequence of all kobuviruses. AiV genotype A sequences were detected in all 137 samples. New sequences of AiV were detected in nine samples, exhibiting 83 % similarity with AiV A846/88, but 95 % similarity with canine kobuvirus (CKV) US-PC0082 in this region. The nucleotide sequences from the VP3 region to the 3' untranslated region (UTR) of sewage sample Y12/2004 were determined. The number of nucleotides in each region was the same as that of CKV. The similarity of the nucleotide (amino acid) identity of a complete VP1 region was 90.5 % (94.8 %) between Y12/2004 and CKV US-PC0082. The phylogenic analyses based on the nucleotide and the deduced amino acid sequences of VP1 and 3D showed that Y12/2004 was independent from AiV, but closely related to CKV. These results suggested that CKV is present in Aichi Prefecture, Japan.