Epidemiology of childhood tuberculosis after ceasing universal Bacillus Calmette-Guérin vaccination.

Universal Bacillus Calmette-Guérin (BCG) vaccination is recommended in countries with high tuberculosis (TB) burden. Nevertheless, several countries have ceased universal BCG vaccination over the past 40 years, with scarce comparative epidemiological analyses regarding childhood TB after the policy change. We analysed data on childhood TB in countries that ceased universal BCG vaccination. Data sources included national/international databases, published papers, annual TB reports, and public health authority websites. Childhood TB notification rate increased in one of seven countries with available data. Pulmonary TB and TB lymphadenitis were the main causes of increasing childhood cases, while changes in severe forms of TB cases were minor. Maintaining high vaccine coverage for the target group was a common challenge after shifting selective vaccination. In some countries showing no increase in childhood TB after a BCG policy change, the majority of childhood TB cases were patients from abroad or those with overseas parents; these countries had changed immigration policies during the same period. Heterogeneity in childhood TB epidemiology was observed after ceasing universal BCG vaccination; several factors might obscure the influence of vaccination policy change. Lessons learned from these countries may aid in the development of better BCG vaccination strategies.

The linkage between medical student readiness for interprofessional learning and interest in community medicine.

OBJECTIVES: The purpose of this study is to investigate the relationship between medical student readiness for interprofessional learning and interest in community medicine prior to incorporating community-oriented interprofessional education into the curriculum. METHODS: A questionnaire was administered to students at Nagasaki University School of Medicine in Japan during each of three consecutive years (N=2244). The Readiness for Interprofessional Learning Scale (RIPLS) was administered in addition to a questionnaire to evaluate interest in community medicine. The Kruskal-Wallis and Steel-Dwass tests were used to determine differences between school years. Correlation between the RIPLS score and interest in community medicine was evaluated with Spearman's rank correlation coefficient. Relationships between RIPLS score and demographic parameters, and interest in community medicine were evaluated with multiple linear regression analysis. RESULTS: Eighty-four percent (1891/2244) of students responded. The RIPLS score was highest in school year 1, followed by year 6, year 5, year 3, and years 4 and 2. Interest in community medicine correlated with the RIPLS score (rs = 0.332, p < 0.001), but less in year 1 (rs = 0.125, p = 0.002) than in other years. RIPLS score was significantly associated with gender, age, school year, interest in community medicine, but not the year that the survey was conducted. CONCLUSIONS: Community-oriented interprofessional education has the potential to improve attitudes towards interprofessional learning. When introducing this promising education into the curriculum from year 1, attracting students' interest in community medicine should be considered.

Estimating the annual risk of tuberculosis infection in Japan from interferon-gamma release assay data.

To assess tuberculosis transmission frequency at a population level, the age-dependent Mantoux test has been used widely to estimate the annual risk of infection (ARI) with Mycobacterium tuberculosis. However, the widespread Bacille Calmette-Guerin (BCG) immunization program implemented in Japan in the 20th century has made natural infections with M. tuberculosis difficult to distinguish from immune responses against this vaccine. Consequently, a recognized alternative method for measuring the frequency of primary infections, the interferon-gamma release assay (IGRA), which partially decays as a function of time after infection, is used. We aimed to estimate the ARI in Japan from IGRA data along with its response decay information using mathematical modeling. Devising a partial differential equation system, we computed the probability of IGRA positivity as a function of time and age, accounting for the time-varying force of infection and decay function of the IGRA response. Jointly estimating the force of infection and the parameters governing the decay function of the IGRA response, we found that the age-dependent increasing pattern of the IGRA response was captured by the proposed simple model, yielding estimates of the time-dependent force of infection. ARI decreased as a function of time in the study subjects for all geographic locations. By the year 2030, our model showed that the median age of infection is predicted to be delayed by 40-50 years compared with that in 1940. The geographic variations in the ARI were striking, ranging from under 0.1% to 0.6% in 2018, which echoes the longstanding notion of highly heterogeneous geographical tuberculosis transmission in Japan.

Unusual and typical features of a novel restorer-of-fertility gene of sugar beet (Beta vulgaris L.).

Male gametogenesis in plants can be impaired by an incompatibility between nuclear and mitochondrial genomes, termed cytoplasmic male sterility (CMS). A sterilizing factor resides in mitochondria, whereas a nuclear factor, Restorer-of-fertility (Rf), restores male fertility. Although a majority of plant Rf genes are thought to encode a family of RNA-binding proteins called pentatrico-peptide repeat (PPR) proteins, we isolated a novel type of Rf from sugar beet. Two BACs and one cosmid clone that constituted a 383-kbp contig covering the sugar beet Rf1 locus were sequenced. Of 41 genes borne by the contig, quadruplicated genes were found to be associated with specific transcripts in Rf1 flower buds. The quadruplicated genes encoded a protein resembling OMA1, a protein known from yeast and mammals to be involved in mitochondrial protein quality control. Construction of transgenic plants revealed that one of the four genes (bvORF20) was capable of restoring partial pollen fertility to CMS sugar beet; the level of restoration was comparable to that evaluated by a crossing experiment. However, the other genes lacked such a capability. A GFP-fusion experiment showed that bvORF20 encoded a mitochondrial protein. The corresponding gene was cloned from rf1rf1 sugar beet and sequenced, and a solitary gene that was similar but not identical to bvORF20 was found. Genetic features exhibited by sugar beet Rf1, such as gene clustering and copy-number variation between Rf1 and rf, were reminiscent of PPR-type Rf, suggesting that a common evolutionary mechanism(s) operates on plant Rfs irrespective of the translation product.