Lancet Microbe最新文献

The incidence of antibiotic-resistant bacterial infections is increasing, and development of new antibiotics has been deprioritised by the pharmaceutical industry. Interdisciplinary research approaches, based on the ecological principles of bacterial fitness, competition, and transmission, could open new avenues to combat antibiotic-resistant infections. Many facultative bacterial pathogens use human mucosal surfaces as their major reservoirs and induce infectious diseases to aid their lateral transmission to new host organisms under some pathological states of the microbiome and host. Beneficial bacterial commensals can outcompete specific pathogens, thereby lowering the capacity of the pathogens to spread and cause serious infections. Despite the clinical relevance, however, the understanding of commensal–pathogen interactions in their natural habitats remains poor. In this Personal View, we highlight directions to intensify research on the interactions between bacterial pathogens and commensals in the context of human microbiomes and host biology that can lead to the development of innovative and sustainable ways of preventing and treating infectious diseases.

Early after the start of the COVID-19 pandemic, the detection of influenza B/Yamagata cases decreased globally. Given the potential public health implications of this decline, in this Review, we systematically analysed data on influenza B/Yamagata virus circulation (for 2020–23) from multiple complementary sources of information. We identified relevant articles published in PubMed and Embase, and data from the FluNet, Global Initiative on Sharing All Influenza Data, and GenBank databases, webpages of respiratory virus surveillance systems from countries worldwide, and the Global Influenza Hospital Surveillance Network. A progressive decline of influenza B/Yamagata detections was reported across all sources, in absolute terms (total number of cases), as positivity rate, and as a proportion of influenza B detections. Sporadically reported influenza B/Yamagata cases since March, 2020 were mostly vaccine-derived, attributed to data entry errors, or have yet to be definitively confirmed. The likelihood of extinction necessitates a rapid response in terms of reassessing the composition of influenza vaccines, enhanced surveillance for B/Yamagata, and a possible change in the biosafety level when handling B/Yamagata viruses in laboratories.

Background

During the 2017–18 influenza season in the USA, there was a high incidence of influenza illness and mortality. However, no apparent antigenic change was identified in the dominant H3N2 viruses, and the severity of the season could not be solely attributed to a vaccine mismatch. We aimed to investigate whether the altered virus properties resulting from gene reassortment were underlying causes of the increased case number and disease severity associated with the 2017–18 influenza season.

Methods

Samples included were collected from patients with influenza who were prospectively recruited during the 2016–17 and 2017–18 influenza seasons at the Johns Hopkins Hospital Emergency Departments in Baltimore, MD, USA, as well as from archived samples from Johns Hopkins Health System sites. Among 647 recruited patients with influenza A virus infection, 411 patients with whole-genome sequences were available in the Johns Hopkins Center of Excellence for Influenza Research and Surveillance network during the 2016–17 and 2017–18 seasons. Phylogenetic trees were constructed based on viral whole-genome sequences. Representative viral isolates of the two seasons were characterised in immortalised cell lines and human nasal epithelial cell cultures, and patients' demographic data and clinical outcomes were analysed.

Findings

Unique H3N2 reassortment events were observed, resulting in two predominant strains in the 2017–18 season: HA clade 3C.2a2 and clade 3C.3a, which had novel gene segment constellations containing gene segments from HA clade 3C.2a1 viruses. The reassortant re3C.2a2 viruses replicated with faster kinetics and to a higher peak titre compared with the parental 3C.2a2 and 3C.2a1 viruses (48 h vs 72 h). Furthermore, patients infected with reassortant 3C.2a2 viruses had higher Influenza Severity Scores than patients infected with the parental 3C.2a2 viruses (median 3·00 [IQR 1·00–4·00] vs 1·50 [1·00–2·00]; p=0·018).

Interpretation

Our findings suggest that the increased severity of the 2017–18 influenza season was due in part to two intrasubtypes, cocirculating H3N2 reassortant viruses with fitness advantages over the parental viruses. This information could help inform future vaccine development and public health policies.

Funding

The Center of Excellence for Influenza Research and Response in the US, National Science and Technology Council, and Chang Gung Memorial Hospital in Taiwan.