How to prevent rubella epidemics and congenital rubella syndrome: lessons from 42 years of longitudinal epidemiology in Osaka Prefecture, Japan (1982-2023).

BACKGROUND: Despite the introduction of rubella-containing vaccine into routine immunization in 1977, rubella has not been eliminated in Japan. This study aimed to validate the immunization strategy and to highlight the crucial elements of elimination program. METHODS: We scrutinized cases of rubella and congenital rubella syndrome (CRS). Additionally, we analyzed the national vaccination coverage, seroprevalence, and number of maternal rubella-related spontaneous or artificial fetal deaths. RESULTS: The shift from selective to universal immunization significantly reduced rubella cases coupled with increased seroprevalence in children. However, rubella resurged in 2012-2013 and 2018-2019, which was virologically and serologically confirmed to be associated with imported rubella virus (RuV) and susceptible males. Although the disease burden of CRS may have been suppressed in the past by the large number of spontaneous or artificial fetal deaths, the incidence rate of CRS was comparable to that of the 1960s to 1980s. Cases of breakthrough infection and CRS were identified in females who were considered to have a history of single-dose vaccination. CONCLUSIONS: Even with universal immunization, future epidemics and severe outcomes cannot be prevented unless immunization gaps are closed. Furthermore, CRS and breakthrough infection are not completely prevented by single-dose vaccination, indicating the need for second-dose vaccination.

Macrophage-1 antigen exacerbates histone-induced acute lung injury and promotes neutrophil extracellular trap formation.

Acute lung injury (ALI), which occurs in association with sepsis, trauma, and coronavirus disease 2019 (COVID-19), is a serious clinical condition with high mortality. Excessive platelet-leukocyte aggregate (PLA) formation promotes neutrophil extracellular trap (NET) release and thrombosis, which are involved in various diseases, including ALI. Macrophage-1 antigen (Mac-1, CD11b/CD18), which is expressed on the surface of leukocytes, is known to promote NET formation. This study aimed to elucidate the role of Mac-1 in extracellular histone-induced ALI. Exogenous histones were administered to Mac-1-deficient mice and wild-type (WT) mice with or without neutrophil or platelet depletion, and several parameters were investigated 1 h after histone injection. Depletion of neutrophils or platelets improved survival time and macroscopic and microscopic properties of lung tissues, and decreased platelet-leukocyte formation and plasma myeloperoxidase levels. These improvements were also observed in Mac-1-/- mice. NET formation in Mac-1-/- bone marrow neutrophils (BMNs) was significantly lower than that in WT BMNs. In conclusion, our findings suggest that Mac-1 is associated with exacerbation of histone-induced ALI and the promotion of NET formation in the presence of activated platelets.

Ido2 Deficiency Exacerbates Motor Impairment and Reduces Aryl Hydrocarbon Receptor Activity through Decreased Kynurenine in a Chronic Demyelinating Mouse Model.

Demyelinating diseases including multiple sclerosis (MS) are chronic inflammatory diseases of the central nervous system. Indoleamine 2,3-dioxygenase 2 (Ido2) is a recently identified as catalytic enzyme involved in the rate-limiting step of the tryptophan-kynurenine pathway that influences susceptibility to inflammatory diseases. However, the pathological role of Ido2 in demyelination remains unclear. In this study, we investigated whether Ido2 deficiency influences the pathogenesis of proteolipid protein transgenic (Plp tg) mice, an animal model of chronic demyelination. Ido2 deficiency exacerbates impairments of motor function in the locomotor activity test, wire hanging test, and rotarod test. Ido2 deficiency caused severe demyelination associated with CD68-positive microglial activation in Plp tg mice. In the cerebellum of Plp tg mice, Ido2 deficiency significantly increased the expression of Tnfα. Ido2 deficiency reduced tryptophan metabolite kynurenine (KYN) levels and subsequent aryl hydrocarbon receptor (AhR) activity, which play an important role in anti-inflammatory response. These results suggest that Ido2 has an important role in preventing demyelination through AhR. Taken together, Ido2 could be a potential therapeutic target for demyelinating diseases.