Search Results (9)

Studies have indicated that there was a disease interaction of pandemic influenza with respiratory tuberculosis (TB) in Malta, which could explain the heightened mortality recorded in young adults. We revisit the 1918/19 influenza and TB syndemic potential on the island of Malta. Borrowing from crisis studies that explore the harvesting effect, we used the method of assessing changes in pre-pandemic, pandemic, fallow, and post-pandemic mortality/life expectancy to reveal the syndemic experience. Pre-pandemic (1914–1917) life expectancy at birth was significantly higher, at 37.91 years, than during the pandemic (1918), when life expectancy dropped to 33.26 years (Z = 10.56, p < 0.0001). Post-pandemic (1919) life expectancy rose to 43.49 years, which was an even longer life expectancy than pre-pandemic (Z = 17.61, p < 0.0001). There were significant changes in TB mortality death rates during the four periods in those of reproductive age. Augmenting our framework for studies of syndemics involving short-term events, we proposed the identification of contributing, driving, and limiting factors. Underlying living conditions contributed to the syndemic. The exacerbation of housing conditions, the economy associated with the First World War, and meteorological measures—temperature, relative humidity, and rainfall—were driving factors. The early implementation of mitigation strategies, such as restrictions on mass gatherings, were limiting factors of the syndemic. Full article

Tuberculosis (TB) continues to be a major public health challenge in low- and middle-income countries (LMICs), where high burdens of coinfections exacerbate the disease’s impact. In 2023, an estimated 8.2 million people were newly diagnosed with tuberculosis worldwide, reflecting an increase from 7.5 million in 2022 and 7.1 million in 2019. In LMICs, limited access to healthcare, inadequate nutrition, and poor living conditions contribute to higher coinfection rates among TB patients, leading to delayed diagnosis and treatment, which in turn exacerbates disease severity and facilitates transmission. This narrative review synthesizes the epidemiology, clinical implications, diagnostic challenges, and management strategies related to TB coinfections with viral pathogens including HIV, SARS-CoV-2, and influenza, bacteria such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa, fungi such as Aspergillus and Candida species, and parasites. This review highlights that overlapping symptoms, immune system compromise, and socioeconomic barriers in LMICs lead to delayed diagnoses and suboptimal treatment outcomes, while also addressing the challenges of managing drug interactions particularly in HIV–TB coinfections and underscoring the need for integrated diagnostic approaches, improved treatment regimens, and strengthened healthcare systems, thereby consolidating current evidence to inform future research priorities and policy interventions aimed at reducing the overall burden of TB and its coinfections in resource-limited settings. Full article

Bile acids (BAs) play a crucial role in the human body’s defense against infections caused by bacteria, fungi, and viruses. BAs counteract infections not only through interactions with intestinal bacteria exhibiting bile salt hydrolase (BSH) activity but they also directly combat infections. Building upon our research group’s previous discoveries highlighting the role of BAs in combating infections, we have initiated an in-depth investigation into the interactions between BAs and intestinal microbiota. Leveraging the existing literature, we offer a comprehensive analysis of the relationships between BAs and 16 key microbiota. This investigation encompasses bacteria (e.g., Clostridioides difficile (C. difficile), Staphylococcus aureus (S. aureus), Escherichia coli, Enterococcus, Pseudomonas aeruginosa, Mycobacterium tuberculosis (M. tuberculosis), Bacteroides, Clostridium scindens (C. scindens), Streptococcus thermophilus, Clostridium butyricum (C. butyricum), and lactic acid bacteria), fungi (e.g., Candida albicans (C. albicans) and Saccharomyces boulardii), and viruses (e.g., coronavirus SARS-CoV-2, influenza virus, and norovirus). Our research found that Bacteroides, C. scindens, Streptococcus thermophilus, Saccharomyces boulardii, C. butyricum, and lactic acid bacteria can regulate the metabolism and function of BSHs and 7α-dehydroxylase. BSHs and 7α-dehydroxylase play crucial roles in the conversion of primary bile acid (PBA) to secondary bile acid (SBA). It is important to note that PBAs generally promote infections, while SBAs often exhibit distinct anti-infection roles. In the antimicrobial action of BAs, SBAs demonstrate antagonistic properties against a wide range of microbiota, with the exception of norovirus. Given the intricate interplay between BAs and intestinal microbiota, and their regulatory effects on infections, we assert that BAs hold significant potential as a novel approach for preventing and treating microbial infections. Full article

The mucosal barrier constitutes a huge surface area, close to 40 m² in humans, located mostly in the respiratory, gastrointestinal and urogenital tracts and ocular cavities. It plays a crucial role in tissue interactions with the microbiome, dietary antigens and other environmental materials. Effective vaccinations to achieve highly protective mucosal immunity are evolving strategies to counteract several serious diseases including tuberculosis, diphtheria, influenzae B, severe acute respiratory syndrome, Human Papilloma Virus infection and Acquired Immune Deficiency Syndrome. Interestingly, one of the reasons behind the rapid spread of severe acute respiratory syndrome coronavirus 2 variants has been the weakness of local immunization at the level of the respiratory mucosa. Mucosal vaccines can outperform parenteral vaccination as they specifically elicit protective mucosal immune responses blocking infection and transmission. In this scenario, chitosan-based nanovaccines are promising adjuvants-carrier systems that rely on the ability of chitosan to cross tight junctions and enhance particle uptake due to chitosan-specific mucoadhesive properties. Indeed, chitosan not only improves the adhesion of antigens to the mucosa promoting their absorption but also shows intrinsic immunostimulant abilities. Furthermore, by finely tuning the colloidal properties of chitosan, it can provide sustained antigen release to strongly activate the humoral defense. In the present review, we agnostically discuss the potential reasons why chitosan-based vaccine carriers, that efficiently elicit strong immune responses in experimental setups and in some pre-clinical/clinical studies, are still poorly considered for therapeutic formulations. Full article

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing, as is research on the molecular mechanisms underlying cellular infection by coronaviruses, with the hope of developing therapeutic agents against this pandemic. Other important respiratory viruses such as 2009 pandemic H1N1 and H7N9 avian influenza virus (AIV), influenza A viruses, are also responsible for a possible outbreak due to their respiratory susceptibility. However, the interaction of these viruses with host cells and the regulation of post-transcriptional genes remains unclear. In this study, we detected and analyzed the comparative transcriptome profiling of SARS-CoV-2, panH1N1 (A/California/07/2009), and H7N9 (A/Shanghai/1/2013) infected cells. The results showed that the commonly upregulated genes among the three groups were mainly involved in autophagy, pertussis, and tuberculosis, which indicated that autophagy plays an important role in viral pathogenicity. There are three groups of commonly downregulated genes involved in metabolic pathways. Notably, unlike panH1N1 and H7N9, SARS-CoV-2 infection can inhibit the m-TOR pathway and activate the p53 signaling pathway, which may be responsible for unique autophagy induction and cell apoptosis. Particularly, upregulated expression of IRF1 was found in SARS-CoV-2, panH1N1, and H7N9 infection. Further analysis showed SARS-CoV-2, panH1N1, and H7N9 infection-induced upregulation of lncRNA-34087.27 could serve as a competitive endogenous RNA to stabilize IRF1 mRNA by competitively binding with miR-302b-3p. This study provides new insights into the molecular mechanisms of influenza A virus and SARS-CoV-2 infection. Full article

Pathogenic intracellular bacteria, parasites and viruses have evolved sophisticated mechanisms to manipulate mammalian host cells to serve as niches for persistence and proliferation. The intracellular lifestyles of pathogens involve the manipulation of membrane-bound organellar compartments of host cells. In this review, we described how normal structural organization and cellular functions of endosomes, endoplasmic reticulum, Golgi apparatus, mitochondria, or lipid droplets are targeted by microbial virulence mechanisms. We focus on the specific interactions of Salmonella, Legionella pneumophila, Rickettsia rickettsii, Chlamydia spp. and Mycobacterium tuberculosis representing intracellular bacterial pathogens, and of Plasmodium spp. and Toxoplasma gondii representing intracellular parasites. The replication strategies of various viruses, i.e., Influenza A virus, Poliovirus, Brome mosaic virus, Epstein-Barr Virus, Hepatitis C virus, severe acute respiratory syndrome virus (SARS), Dengue virus, Zika virus, and others are presented with focus on the specific manipulation of the organelle compartments. We compare the specific features of intracellular lifestyle and replication cycles, and highlight the communalities in mechanisms of manipulation deployed. Full article

The integrin associated protein (CD47) is a widely and moderately expressed glycoprotein in all healthy cells. Cancer cells are known to induce increased CD47 expression. Similar to cancer cells, all immune cells can upregulate their CD47 surface expression during infection. The CD47-SIRPa interaction induces an inhibitory effect on macrophages and dendritic cells (dendritic cells) while CD47-thrombospondin-signaling inhibits T cells. Therefore, the disruption of the CD47 interaction can mediate several biologic functions. Upon the blockade and knockout of CD47 reveals an immunosuppressive effect of CD47 during LCMV, influenza virus, HIV-1, mycobacterium tuberculosis, plasmodium and other bacterial pneumonia infections. In our recent study we shows that the blockade of CD47 using the anti-CD47 antibody increases the activation and effector function of macrophages, dendritic cells and T cells during viral infection. By enhancing both innate and adaptive immunity, CD47 blocking antibody promotes antiviral effect. Due to its broad mode of action, the immune-stimulatory effect derived from this antibody could be applicable in nonresolving and (re)emerging infections. The anti-CD47 antibody is currently under clinical trial for the treatment of cancer and could also have amenable therapeutic potential against infectious diseases. This review highlights the immunotherapeutic targeted role of CD47 in the infectious disease realm. Full article

Tuberculosis (TB) mortality declined after the 1918 pandemic, suggesting that influenza killed those who would have died from TB. Few studies have analyzed TB as a direct risk factor for 1918 influenza morbidity and mortality by age and sex. We study the impacts of TB on influenza-like illness (% of population sick) and case fatality (% of cases dying) by age and sex through case-control comparisons of patients (N = 201) and employees (N = 97) from two Norwegian sanatoriums. Female patients, patients at Landeskogen sanatorium, and patients aged 10–39 years had significantly lower morbidity than the controls. None of the 62 sick employees died, while 15 of 84 sick patients did. The case-control difference in case fatality by sex was only significant for females at Lyster sanatorium and females at both sanatoriums combined. Non-significant case-control differences in case fatality for males were likely due to small samples. Patients 20–29 years for both sexes combined at Lyster sanatorium and at both sanatoriums combined, as well as females 20–29 years for both sanatoriums combined, had significantly higher case fatality. We conclude that TB was associated with higher case fatality, but morbidity was lower for patients than for employees. The results add to the study of interactions between bacterial and viral diseases and are relevant in preparing for pandemics in TB endemic areas. Full article

Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents. Full article