Clinical Microbiology Reviews最新文献

SUMMARYAntivirals play important roles in restricting viral diseases. Nevertheless, they act on a relatively limited number of viruses and occasionally display partial effectiveness in some tissues or against escape variants. Although vaccination remains the most cost-effective approach for preventing microbial diseases, developing prophylactic or therapeutic solutions for pathogens, such as herpes simplex viruses (HSVs), that effectively reduce their clinical manifestations in the skin has proven exceptionally challenging despite extensive research. Alternatively, a less explored approach for tackling HSV skin infection involves using topical immunomodulatory molecules to potentiate the host's innate antiviral immune responses. When applied directly to herpetic skin lesions where viral antigen is present, this strategy has the potential to elicit virus-specific adaptive immunity. Based on currently available data, we foresee substantial potential for this approach in addressing HSV skin infections, along with additional prospects to advance understanding of skin biology and apply relevant new findings to other dermatological conditions. However, due to the limited number of case studies evaluating this method and its safety profile, particularly in immunocompromised individuals and pregnant women, further research is crucial, especially to assess the effects of immunomodulators in these vulnerable populations. Here, we revisit and discuss the use of immunomodulatory molecules for potentiating the host immune response against HSV skin infection and call for action for increased research and clinical trials regarding the possible benefits of this latter strategy for treating HSV cutaneous disease and recurrences. We also revisit and discuss antivirals and vaccine candidates against HSVs.

SUMMARYMore than 40 types of sexually transmitted human papillomavirus (HPV) infect the oropharyngeal and anogenital mucosa-high-risk types are associated with precancerous and cancerous lesions of the cervix, vagina, vulva, penis, anus, and oropharynx, and low-risk types cause non-malignant disease, such as anogenital warts. Though most HPV infections resolve spontaneously, immunodeficiencies may result in persistent infection and increased risk of HPV-related sequelae. The mechanism by which HPV results in malignant transformation is multifaceted, involving interactions with numerous cellular pathways, the host immune system, and potentially the host microbiome. Vaccination against HPV is highly efficacious in the prevention of infection and related sequelae, and there now exist several approved formulations that protect against both high- and low-risk types. Despite the advent of vaccination, early detection and treatment of cervical and anal precancerous lesions continues to be integral to secondary prevention-molecular HPV testing, cytology, and tissue biopsy allow for triaging of patients, after which appropriate treatment with close follow-up can avert cancer development.

SUMMARYXenotransplantation, the transplantation of living organs, tissues, or cells between species, carries the potential to address the global shortage of human organs for patients with end-stage organ failure. Recent advances in genetic engineering have improved prospects for clinical xenotransplantation by reducing immune and inflammatory responses to grafts, controlling coagulation on endothelial surfaces, and modifying viral risks, including the porcine endogenous retrovirus (PERV). Management of infectious risks posed by clinical xenotransplantation requires meticulous attention to the biosecure breeding and microbiological surveillance of source animals and recipients and consideration of novel infection control requirements. Infectious risks in xenotransplantation stem from both known human pathogens in immunosuppressed transplant recipients and from porcine organisms for which the clinical manifestations, microbial assays, and therapies are generally limited. Both known and unknown zoonoses may be transmitted from pigs to humans. Some pig-specific pathogens do not infect human cells but have systemic manifestations when active within the xenograft, including porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV), which contributes to graft rejection and consumptive coagulopathy. The role of porcine endogenous retrovirus (PERV) in humans remains uncertain despite the absence of documented transmissions and the availability of swine with inactivated genomic PERV. New technologies, such as metagenomic sequencing and multi-omics approaches, will be essential for detection of novel infections and for understanding interactions between the xenograft, the host's immune system, and potential pathogens. These approaches will allow development of infection control protocols, pathogen surveillance requirements, and tailored antimicrobial therapies to enhance the safety and success of clinical xenotransplantation.

SUMMARYThe human pathogen Neisseria meningitidis (Nm) is the causative agent of invasive meningococcal disease (IMD), usually presenting as meningitis, bacteremia, or sepsis. Unlike Neisseria gonorrhoeae, antibiotic resistance in Nm has developed slowly. However, in the last two decades and with the reemergence of IMD following the COVID-19 pandemic, antibiotic-resistant Nm isolates, especially to penicillin and fluoroquinolones, have progressively increased. Recent worldwide studies of penicillin intermediate and resistant Nm isolates and the PubMLST global database reveal a notable increase in fully penicillin-resistant isolates since 2016, mediated by mosaic penA alleles or the β-lactamase genes bla_ROB-1 and bla_TEM-1. Fluoroquinolone-resistant isolates, mediated by gyrA mutations, have increased since 2005. Also, while still exceptionally rare, four Nm isolates have been identified with third-generation cephalosporin-resistance since 2011. We review the emergence of antibiotic resistance determinants and lineages in Nm, the resistance to agents previously or currently used in treatment or chemoprophylaxis, and summarize updated treatment and prevention guidelines for IMD. Special populations (e.g., individuals on complement inhibitors) and antibiotic resistance in Nm urethritis isolates are also reviewed. The increasing number of resistant Nm isolates worldwide affects chemoprophylaxis and treatment options for IMD and emphasizes the need for enhanced global surveillance of antibiotic resistance in Nm.