Guidelines for Identifying Homologous Recombination Events in Influenza A Virus

The rapid evolution of influenza viruses occurs both clonally and non-clonally through a variety of genetic mechanisms and selection pressures. The non-clonal evolution of influenza viruses comprises relatively frequent reassortment among gene segments and a more rarely reported process of non-homologous RNA recombination. Homologous RNA recombination within segments has been proposed as a third such mechanism, but to date the evidence for the existence of this process among influenza viruses has been both weak and controversial. As homologous recombination has not yet been demonstrated in the laboratory, supporting evidence, if it exists, may come primarily from patterns of phylogenetic incongruence observed in gene sequence data. Here, we review the necessary criteria related to laboratory procedures and sample handling, bioinformatic analysis, and the known ecology and evolution of influenza viruses that need to be met in order to confirm that a homologous recombination event occurred in the history of a set of sequences. To determine if these criteria have an effect on recombination analysis, we gathered 8307 publicly available full-length sequences of influenza A segments and divided them into those that were sequenced via the National Institutes of Health Influenza Genome Sequencing Project (IGSP) and those that were not. As sample handling and sequencing are executed to a very high standard in the IGSP, these sequences should be less likely to be exposed to contamination by other samples or by laboratory strains, and thus should not exhibit laboratory-generated signals of homologous recombination. Our analysis shows that the IGSP data set contains only two phylogenetically-supported single recombinant sequences and no recombinant clades. In marked contrast, the non-IGSP data show a very large amount of potential recombination. We conclude that the presence of false positive signals in the non-IGSP data is more likely than false negatives in the IGSP data, and that given the evidence to date, homologous recombination seems to play little or no role in the evolution of influenza A viruses

Antimicrobial resistance surveillance in low- and middle-income countries: Progress and challenges in eight South Asian and Southeast Asian countries

SUMMARYAntimicrobial resistance (AMR) is a serious global health threat and is predicted to cause significant health and economic impacts, particularly in low- and middle-income countries (LMICs). AMR surveillance is critical in LMICs due to high burden of bacterial infections; however, conducting AMR surveillance in resource-limited settings is constrained by poorly functioning health systems, scarce financial resources, and lack of skilled personnel. In 2015, the United Nations World Health Assembly endorsed the World Health Organization\u27s Global Action Plan to tackle AMR; thus, several countries are striving to improve their AMR surveillance capacity, including making significant investments and establishing and expanding surveillance networks. Initial data generated from AMR surveillance networks in LMICs suggest the high prevalence of resistance, but these data exhibit several shortcomings, such as a lack of representativeness, lack of standardized laboratory practices, and underutilization of microbiology services. Despite significant progress, AMR surveillance networks in LMICs face several challenges in expansion and sustainability due to limited financial resources and technical capacity. This review summarizes the existing health infrastructure affecting the establishment of AMR surveillance programs, the burden of bacterial infections demonstrating the need for AMR surveillance, and current progress and challenges in AMR surveillance efforts in eight South and Southeast Asian countries

Self reported stressful life events and exacerbations in multiple sclerosis: prospective study

OBJECTIVE: To study the relation between self reported stressful life events not related to multiple sclerosis and the occurrence of exacerbations in relapsing-remitting multiple sclerosis. DESIGN: Longitudinal, prospective cohort study. SETTING: Outpatient clinic of department of neurology in the Netherlands. PARTICIPANTS: Patients aged 18-55 with relapsing-remitting multiple sclerosis, who could walk with a cane or better (score of 0-6.0 on the expanded disability status scale), and had had at least two exacerbations in 24 months before inclusion in the study. Patients with other serious conditions were excluded. MAIN OUTCOME MEASURE: The risk of increased disease activity as measured by the occurrence of exacerbations after weeks with stressful events. RESULTS: Seventy out of 73 included patients (96%) reported at least one stressful event. In total, 457 stressful life events were reported that were not related to multiple sclerosis. Average follow up time was 1.4 years. Throughout the study, 134 exacerbations occurred in 56 patients and 136 infections occurred in 57 patients. Cox regression analysis with time dependent variables showed that stress was associated with a doubling of the exacerbation rate (relative risk 2.2, 95% confidence interval 1.2 to 4.0, P = 0.014) during the subsequent four weeks. Infections were associated with a threefold increase in the risk of exacerbation, but this effect was found to be independent of experienced stress. CONCLUSION: Stressful events were associated with increased exacerbations in relapsing-remitting multiple sclerosis. This association was independent of the triggering effect of infections on exacerbations of multiple sclerosis

Does sunlight drive seasonality of TB in Vietnam? A retrospective environmental ecological study of tuberculosis seasonality in Vietnam from 2010 to 2015.

BACKGROUND: Tuberculosis (TB) is a major global health burden, with an estimated quarter of the world's population being infected. The World Health Organization (WHO) launched the "End TB Strategy" in 2014 emphasising knowing the epidemic. WHO ranks Vietnam 12th in the world of high burden countries. TB spatial and temporal patterns have been observed globally with evidence of Vitamin D playing a role in seasonality. We explored the presence of temporal and spatial clustering of TB in Vietnam and their determinants to aid public health measures. METHODS: Data were collected by the National TB program of Vietnam from 2010 to 2015 and linked to the following datasets: socio-demographic characteristics; climatic variables; influenza-like-illness (ILI) incidence; geospatial data. The TB dataset was aggregated by province and quarter. Descriptive time series analyses using LOESS regression were completed per province to determine seasonality and trend. Harmonic regression was used to determine the amplitude of seasonality by province. A mixed-effect linear model was used with province and year as random effects and all other variables as fixed effects. RESULTS: There were 610,676 cases of TB notified between 2010 and 2015 in Vietnam. Heat maps of TB incidence per quarter per province showed substantial temporal and geospatial variation. Time series analysis demonstrated seasonality throughout the country, with peaks in spring/summer and troughs in autumn/winter. Incidence was consistently higher in the south, the three provinces with the highest incidence per 100,000 population were Tay Ninh, An Giang and Ho Chi Minh City. However, relative seasonal amplitude was more pronounced in the north. Mixed-effect linear model confirmed that TB incidence was associated with time and latitude. Of the demographic, socio-economic and health related variables, population density, percentage of those under 15 years of age, and HIV infection prevalence per province were associated with TB incidence. Of the climate variables, absolute humidity, average temperature and sunlight were associated with TB incidence. CONCLUSION: Preventative public health measures should be focused in the south of Viet Nam where incidence is highest. Vitamin D is unlikely to be a strong driver of seasonality but supplementation may play a role in a package of interventions

Implementing the WHO AWaRe antibiotic book guidance in lower-resource settings: the case of the Lao PDR

In 2022, WHO released the WHO AWaRe (Access, Watch, Reserve) antibiotic book to promote the rational use of antibiotics. Here, we review the AWaRe antibiotic book from the perspective of implementation in low-resource settings, using the Lao PDR (Laos) as a case study. Not all recommendations in the AWaRe antibiotic book match the epidemiology of infectious diseases and antimicrobial susceptibility patterns in Laos and other low- and middle-income countries (LMICs), e.g. melioidosis, rickettsial disease and leptospirosis are common causes of sepsis and febrile illness in Laos but do not feature in the AWaRe book. Conversely, some infectious diseases like Clostridioides difficile-associated diarrhoea are in the AWaRe antibiotic book but rarely considered in Laos with no diagnostic tests available. Only 29/39 antibiotics in the AWaRe book are available in Laos, with no Reserve group antimicrobials available. The AWaRe book stimulates countries such as Laos to consider alternative diagnoses and include additional antimicrobials in the national essential medicines list (NEML). However, it should be updated to include regional important pathogens that are not included. Comprehensive antibiotic use guidelines alone might not assure appropriate use or control overuse of antibiotics. Access to antibiotics is challenging in low-resource settings in terms of unavailability in the country (low demand or small market size), patchy access, especially for those living in remote areas, and unaffordability. All these systemic factors can contribute to inappropriate use of antibiotics. Improved access to antibiotics, strengthening diagnostic capacity and promoting antibiotic stewardship should be combined

Effectiveness of oseltamivir on disease progression and viral RNA shedding in patients with mild pandemic 2009 influenza A H1N1: opportunistic retrospective study of medical charts in China

Objective To describe the clinical features and effectiveness of oseltamivir on disease progression and viral RNA shedding in patients with mild pandemic 2009 influenza A(H1N1) virus infection