The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1-9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2-7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3-25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11-21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained. Bill & Melinda Gates Foundation.

Phage therapy is one of the alternatives to treat infections caused by both antibiotic-sensitive and antibiotic-resistant bacteria, with no or low toxicity to patients. It was started a century ago, although rapidly growing bacterial antimicrobial resistance, resulting in high levels of morbidity, mortality, and financial cost, has initiated the revival of phage therapy. It involves the use of live lytic, bioengineered, phage-encoded biological products, in combination with chemical antibiotics to treat bacterial infections. Importantly, phages will be removed from the body within seven days of clearing an infection. They target specific bacterial strains and cause minimal disruption to the microbial balance in humans. Phages for medication must be screened for the absence of resistant genes, virulent genes, cytotoxicity, and their interaction with the host tissue and organs. Since they are immunogenic, applying a high phage titer for therapy exposes them and activates the host immune system. To date, no serious side effects have been reported with human phage therapy. In this review, we describe phage–phagocyte interaction, bacterial resistance to phages, how phages conquer bacterial resistance, the role of genetic engineering and other technologies in phage therapy, and the therapeutic application of modified phages and phage-encoded products. We also highlight the comparison of antibiotics and lytic phage therapy, the pros and cons of phage therapy, determinants of human phage therapy trials, phage quality and safety requirements, phage storage and handling, and current challenges in phage therapy.

Extracellular vesicles (EV) can be produced as part of pathology and physiology with increased amounts in pathological conditions. EVs can carry and transfer cargo such as proteins, nucleic acids, and lipids to target cells and mediate intercellular communication resulting in modulation of gene expression, signaling pathways, and phenotype of recipient cells. EVs greatly influence the extracellular environment and the immune response. Their immunomodulatory properties are crucial in rheumatoid arthritis (RA), a condition marked by dysregulated immune response. EVs can modulate the functions of innate and adaptive immune cells in RA pathogenesis. Differentially expressed EV-associated molecules in RA, such as microRNAs (miRNAs), long-noncoding RNAs (lncRNAs), messenger RNAs (mRNAs) and proteins are promising markers to diagnose the disease. miRNA, lncRNA, and circular RNA (circRNA) cargos in EV regulate inflammation and the pathogenic functions of RA fibroblast-like synoviocytes (RA-FLS). Downregulated molecules in RA tissue and drugs can be encapsulated in EVs for RA therapy. This review provides an updated overview of EVs’ immunomodulatory, diagnostic, and therapeutic roles, particularly emphasizing mesenchymal stem cell-derived EVs (MSC-EVs).

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has rapidly spread across the world since its first emergence in China in late 2019. It is a major public health concern with no effective treatct 3ments. The immunopathology of SARS-CoV-2 is associated with an excessive inflammatory response. Macrophage activation syndrome (MAS) is also associated with the severity of the disease in SARS-CoV-2-infected patients. Neopterin is a macrophage activation marker produced by monocytes and macrophages upon activation by interferon-gamma (IFN-γ). Neopterin is a well-established marker in a variety of diseases, and recent evidence indicates that it could be helpful in early prediction of the severity of COVID-19 disease and serve as a prognostic marker. Here, we outline the role of macrophage activation syndrome in the pathogenesis of SARS-CoV-2 and suggest that neopterin could be used as a biomarker for progression of COVID-19.

Introduction. Prisoners in Sub-Saharan Africa (SSA) are at a high risk of tuberculosis (TB) infection due to overcrowding and poor ventilation. Consequently, TB is a leading cause of morbidity and mortality in prison, and many inmates face a number of barriers to TB control and had limited information in the region. Thus, the aim of this systematic review and meta-analysis was to estimate the overall pooled prevalence of pulmonary TB and predictors among prison inmates in SSA. Methods. From 2006 to 2019, a systematic review and meta-analysis was conducted using various databases, including PubMed, Embase, Web of Science, and Scopus. The data were extracted in Microsoft Excel using a standardized data extraction format, and the analysis was carried out with STATA version 14. To detect heterogeneity across studies, the and the Cochrane test statistics were computed. To determine the overall prevalence of TB and predictors among prison populations, a random effect meta-analysis model was used. Results. Of the 3,479 retrieved articles, 37studies comprising 72,844 inmates met the inclusion criteria. The pooled prevalence of pulmonary TB among prison inmates in SSA was 7.74% (95% CI: 6.46-8.47). In the subgroup analysis, the highest prevalence was found in the Democratic Republic Congo (DRC) (19.72%) followed by Zambia (11.68%) and then Ethiopia (9.22%). TB/HIV coinfection (OR 4.99 (95% CI: 2.60-9.58)), Body mass index ( ) (OR 3.62 (95% CI: 2.65-6.49)), incarceration (OR 4.52 (95% CI: 2.31-5.68)), and previous TB exposure (OR 2.43 (95% CI: 1.61-3.56)) had higher odds of pulmonary TB among inmates. Conclusion. The prevalence of pulmonary TB among SSA prison inmates was found to be high as compared to total population. TB/HIV coinfection, BMI, incarceration duration, and TB exposure were all predictors with pulmonary tuberculosis in prison inmates. As a result, emphasizing early screening for prisoners at risk of pulmonary TB is an important point to achieving global TB commitments in resource-limited settings.