Mary Garvey

Globally, invasive fungal diseases are increasing in incidence and are associated with high rates of mortality. A lack of effective diagnostic protocols, antifungal resistance and poor antifungal stewardship contribute to negative outcomes. Aspergillus, Candida, Cryptococcus, and Pneumocystis are the most common pathogens associated with fatal fungal diseases. These species are responsible for 90% of reported invasive fungal deaths globally. Fungal species employ a diverse and effective array of virulence factors to sabotage, evade, and manipulate host immune systems, allowing for colonisation and dissemination in vivo. Invasive fungal infections are clinically challenging, as they penetrate organs and deep tissues, contributing to the aetiology of respiratory tract, endocarditis, meningitis, and medical device infections and resulting in false negative diagnostic attempts. The 2025 WHO report outlines a lack of diagnostic and therapeutic options available, especially in low-to-middle-income countries. Geographical and economic factors impact fungal disease and mortality rates. There is an urgent need for new approaches to combat fungal diseases clinically with improved biocompatibility profiles. This timely review discusses the prevalent invasive fungal species, namely, Candida, Aspergillus, Cryptococcus, and Pneumocystis, which have high mortality rates, as identified by the WHO priority pathogen list, and discusses recent advances in the treatment of fungal diseases. This dissemination of information is an important aspect of the United Nations Sustainable Development Goals (SDGs) and One Health.

Rates of foodborne infectious disease are increasing globally. The One Health zoonoses report shows increasing cases of shigatoxigenic Escherichia coli, campylobacteriosis, salmonellosis and listeriosis in the last 5 years. The ESKAPE pathogens are the top priority due to their alarming rate of resistance to broad-spectrum beta-lactams, carbapenems, glycopeptides, fluoroquinolones, aminoglycosides and biocide solutions. Research assessing alternative biocontrol options highlight the advantages of bacteriophages in the control of resistant bacterial species. Phage formulations including ListShield^TM and SalmoFresh^TM have gained FDA approval for food production. As biocontrol agents, however, phages are limited by their specificity in a multispecies environment, the presence of environmental variables and bacterial resistance mechanisms. Genetic modification and the use of phage cocktails aim to overcome such limitations. Future research is warranted in a harmonised approach supported by a defined legal framework to establish best formulation and exposure protocols. This review discusses phages as biocontrol agents in the control of high-risk pathobionts associated with foodborne illness. Pathobionts associated with bovine livestock are discussed due to the morbidity and incidence of disease associated with such pathogens.

Despite improved diagnostic and treatment protocols, cancer remains a leading cause of morbidity and mortality globally. There are increasing rates of certain cancer types, including the highly drug-resistant colorectal cancer, in younger population cohorts. Therapeutic advances in oncology have led to the application of immunotherapy-based agents, including checkpoint inhibitors, antibodies, and adoptive cell therapies. Such immunotherapy approaches are greatly hindered by the tumour microenvironment and lack of specificity. Therapeutic vaccines are an innovative and rapidly advancing area of oncology, having potential for application as mono- and combined therapy in clinical settings, offering long term efficacy against disease recurrence. Advances in vaccine production using gene editing and bioprocessing techniques allows for novel vaccine types, including protein-based subunit vaccines, virus-like particle vaccines, and viral vector- and nucleic acid-based (RNA and DNA) vaccines. Cancer vaccines are designed to deliver specific tumour antigens, which activate anti-cancer cytotoxic T cells and helper T cells to produce immune memory, providing long term anti-cancer action. When coupled with advances in machine learning and artificial intelligence, anti-cancer vaccines may revolutionise oncology protocols and improve patient prognosis. This review aims to discuss current immunotherapy options in cancer treatment and recent advances in anti-cancer vaccine modalities.

The prevention of human infectious diseases associated with waterborne pathogens is reliant on the effective disinfection of water supplies by drinking water treatment plants and adequately maintained distribution networks. For decades, the chlorination of water has safeguarded public health, where chlorine is broadly applied in both water disinfection and food production facilities, including the dairy industry, from farm to fork. The identification of chlorine disinfection byproducts in water supplies and dairy food produce is of great concern, however, due to their cytotoxic, genotoxic, mutagenic, teratogenic, and potential endocrine-disrupting activity. The association between the trihalomethanes (THMs) and haloacetic acids (HAAs) and tumour formation is documented and has led to the implementation of maximum contaminant levels enforced by the European Union. Furthermore, chlorine resistance in bacterial species is associated with multidrug resistance in clinically relevant pathogens, where antibiotic- and biocidal-resistant genes are also environmental pollutants. Increasing the concentration of chlorine to surmount this resistance will ultimately lead to increasing concentrations of byproducts in both water and food products, exceeding the EU requirements. This article provides insight into chlorine DBPs as a toxicological public health risk and the relationship between chlorine resistance and antibiotic resistance in microbes relevant to dairy food production.

The World Health Organization announced critically important bacterial and fungal pathogens displaying alarming levels of antimicrobial resistance, which currently represent difficult-to-treat cases of morbidity. Within this grouping, the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are causative of significant morbidity and mortality. Studies described herein demonstrate the presence of critically important fungal and ESKAPE bacterial species in companion animals which are zoonotic in nature. The relationship between the environment, animals, and human infectious disease has long been recognized as part of One Health. This research investigates the resistance patterns of isolated zoonotic pathogens using recognized in vitro methodologies, namely disk diffusion, minimum inhibitory concentration testing, and genetic screening. Antibiotic susceptibility testing and gene analysis demonstrated an association between multi-drug resistance and extended beta spectrum lactamase production in critical-priority bacteria. Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa exhibit great levels of multi-drug resistance. Fungal isolates demonstrated high levels of resistance, with Amphotericin B proving the most effective antifungal agent investigated. The level of antimicrobial resistance present in clinically relevant bacterial and fungal pathogens isolated from animal cases of morbidity in this study is alarming. In conclusion, this study shows that animals can act as a reservoir facilitating the transmission of antibiotic-resistant pathogens and genes zoonotically.

Endometriosis is an oestrogen-dependent inflammatory disease affecting menstruating women, with varying levels of severity. Oestrogen dysregulation is responsible for chronic inflammation, angiogenesis, endometrial lesion development, progression, and infertility during menarche in afflicted women. The inflammatory mediators associated with this chronic painful disease have been established, with research also indicating the relationship between dysbiosis and disease manifestation. Endometriosis is also present with several painful comorbidities, including endometrial cancer, cardiovascular disease, and autoimmunity. The lack of specific and sensitive non-invasive diagnostic procedures, coupled with poor response to current therapeutic approaches, means that treatment needs remain unmet. Surgical procedures are performed to remove endometriosis ectopic lesions, for which the recurrence rate of disease is up to 50%, with certain patients exhibiting no alleviation of symptoms. This review aims to outline the aetiology of endometriosis, detailing novel diagnostic approaches and potential therapeutic approaches, namely advanced therapeutic medical products (ATMPs), including stem cell therapy and clustered regularly interspaced short palindromic repeats (CRISPR) gene editing. This timely review also provides novel insights into the important recent modalities which may be applied for the diagnosis and therapeutic response of endometriosis, including biomarkers, microfluidic platforms, and organoid systems. Undoubtedly, reliable, reproducible, sensitive, and specific models of endometriosis in humans are urgently needed to investigate and detail the aetiology of this debilitating disease.

Neonatal infectious disease continues to result in high rates of infant morbidity and mortality. Early- and late-onset disease represent difficult to detect and difficult to treat illnesses, particularly when antimicrobial resistant pathogens are present. Newborns are immunodeficient and are at increased risk of vertical and horizontal infection, with preterm infants increasingly susceptible. Additional risk factors associated with infection include prolonged use of a central catheter and/or ventilation, congenital abnormalities, admittance to intensive care units, and the use of broad-spectrum antibiotics. There is increasing recognition of the importance of the host microbiome and dysbiosis on neonatal infectious disease, including necrotising enterocolitis and sepsis in patients. Current diagnostic methods rely on blood culture, which is unreliable, time consuming, and can result in false negatives. There is a lack of accurate and reliable diagnostic tools available for the early detection of infectious disease in infants; therefore, efficient triage and treatment remains challenging. The application of biomarkers, machine learning, artificial intelligence, biosensors, and microfluidics technology, may offer improved diagnostic methodologies. Point-of-care devices, such diagnostic methodologies, may provide fast, reliable, and accurate diagnostic aids for neonatal patients. This review will discuss neonatal infectious disease as impacted by antimicrobial resistance and will highlight novel point-of-care diagnostic options.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, commonly associated with nosocomial transmission. Gram-negative bacterial species are particularly problematic due to the release of the lipopolysaccharide toxins upon cell death. The lipopolysaccharide toxin of E. coli has a greater immunogenic potential than that of other Gram-negative bacteria. The resultant dysregulation of the immune system is associated with organ failure and mortality, with pregnant women, ICU patients, and neonates being particularly vulnerable. Additionally, sepsis recovery patients have an increased risk of re-hospitalisation, chronic illness, co-morbidities, organ damage/failure, and a reduced life expectancy. The emergence and increasing prevalence of antimicrobial resistance in bacterial and fungal species has impacted the treatment of sepsis patients, leading to increasing mortality rates. Multidrug resistant pathogens including vancomycin-resistant Enterococcus, beta lactam-resistant Klebsiella, and carbapenem-resistant Acinetobacter species are associated with an increased risk of mortality. To improve the prognosis of sepsis patients, predominantly high-risk neonates, advances must be made in the early diagnosis, triage, and control of sepsis. The identification of suitable biomarkers and biomarker combinations, coupled with machine learning and artificial intelligence, show promise in early detection protocols. Rapid diagnosis of sepsis in patients is essential to inform on clinical treatment, especially with resistant infectious agents. This timely review aims to discuss sepsis prevalence, aetiology, and recent advances towards disease mitigation and control.

The human gastrointestinal tract houses a diverse range of microbial species that play an integral part in many biological functions. Several preclinical studies using germ-free mice models have demonstrated that the gut microbiome profoundly influences carcinogenesis and progression. Colorectal cancer appears to be associated with microbial dysbiosis involving certain bacterial species, including F. nucleatum, pks+ E. coli, and B. fragilis, with virome commensals also disrupted in patients. A dysbiosis toward these pro-carcinogenic species increases significantly in CRC patients, with reduced numbers of the preventative species Clostridium butyicum, Roseburia, and Bifidobacterium evident. There is also a correlation between Clostridium infection and CRC. F. nucleatum, in particular, is strongly associated with CRC where it is associated with therapeutic resistance and poor outcomes in patients. The carcinogenic mode of action of pathogenic bacteria in CRC is a result of genotoxicity, epigenetic alterations, ROS generation, and pro-inflammatory activity. The aim of this review is to discuss the microbial species and their impact on colorectal cancer in terms of disease initiation, progression, and metastasis. The potential of anticancer peptides as anticancer agents or adjuvants is also discussed, as novel treatment options are required to combat the high levels of resistance to current pharmaceutical options.

Healthcare-associated infections caused by multi-drug-resistant pathogens are increasing globally, and current antimicrobial options have limited efficacy against these robust species. The WHO details the critically important bacterial and fungal species that are often associated with medical device HAIs. The effective sterilization of medical devices plays a key role in preventing infectious disease morbidity and mortality. A lack of adherence to protocol and limitations associated with each sterilization modality, however, allows for the incidence of disease. Furthermore, issues relating to carcinogenic emissions from ethylene oxide gas (EtO) have motivated the EPA to propose limiting EtO use or seeking alternative sterilization methods for medical devices. The Food and Drug Administration supports the sterilization of healthcare products using low-temperature VH₂O₂ as an alternative to EtO. With advances in biomaterial and medical devices and the increasing use of combination products, current sterilization modalities are becoming limited. Novel approaches to disinfection and sterilization of medical devices, biomaterials, and therapeutics are warranted to safeguard public health. Bacteriophages, endolysins, and antimicrobial peptides are considered promising options for the prophylactic and meta-phylactic control of infectious diseases. This timely review discusses the application of these biologics as antimicrobial agents against critically important WHO pathogens, including ESKAPE bacterial species.