Clinical Microbiology Reviews最新文献

Neisseria gonorrhoeae infection is an important public health issue, with an annual global incidence of 87 million. N. gonorrhoeae infection causes significant morbidity and can have serious long-term impacts on reproductive and neonatal health and may rarely cause life-threatening disease. Global rates of N. gonorrhoeae infection have increased over the past 20 years. Importantly, rates of antimicrobial resistance to key antimicrobials also continue to increase, with the United States Centers for Disease Control and Prevention identifying drug-resistant N. gonorrhoeae as an urgent threat to public health. This review summarizes the current evidence for N. gonorrhoeae vaccines, including historical clinical trials, key N. gonorrhoeae vaccine preclinical studies, and studies of the impact of Neisseria meningitidis vaccines on N. gonorrhoeae infection. A comprehensive survey of potential vaccine antigens, including those identified through traditional vaccine immunogenicity approaches, as well as those identified using more contemporary reverse vaccinology approaches, are also described. Finally, the potential epidemiological impacts of a N. gonorrhoeae vaccine and research priorities for further vaccine development are described.

Pneumocystis jirovecii is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest risk of Pneumocystis jirovecii pneumonia (PCP). While guidelines have approached the diagnosis, prophylaxis, and management of PCP, the numerous studies of PCP in PWH are dominated by the 1980s and 1990s. As such, most studies have included younger male populations, despite PCP affecting both sexes and a broad age range. Many studies have been small and observational in nature, with an overall lack of randomized controlled trials. In many jurisdictions, and especially in low- and middle-income countries, the diagnosis can be challenging due to lack of access to advanced and/or invasive diagnostics. Worldwide, most patients will be treated with 21 days of high-dose trimethoprim sulfamethoxazole, although both the dose and the duration are primarily based on historical practice. Whether treatment with a lower dose is as effective and less toxic is gaining interest based on observational studies. Similarly, a 21-day tapering regimen of prednisone is used for patients with more severe disease, yet other doses, other steroids, or shorter durations of treatment with corticosteroids have not been evaluated. Now with the widespread availability of antiretroviral therapy, improved and less invasive PCP diagnostic techniques, and interest in novel treatment strategies, this review consolidates the scientific body of literature on the diagnosis and management of PCP in PWH, as well as identifies areas in need of more study and thoughtfully designed clinical trials.

There is a growing need for solid organ transplantation (SOT) for people living with human immunodeficiency virus (HIV). With the advent of antiretroviral therapy, people living with HIV are experiencing increased life expectancies and are, therefore, developing more comorbidities, including end-stage organ disease. In cases of advanced organ failure, SOT is often the best therapeutic option to improve quality of life and overall survival. As organ shortages persist, transplantation of organs from donors with HIV to recipients with HIV has become a potential therapeutic option. This article first reviews the current state of organ transplantation from donors without HIV to recipients with HIV (HIV D-/R+) by organ and discusses key lessons learned from these transplant trials, including those about drug-drug interactions, rejection, and opportunistic infections. It then explores transplantation from donors with HIV to recipients with HIV (HIV D+/R+), a new frontier. Finally, it investigates challenges of implementation, including public awareness and regulatory requirements, and explores future directions for SOT in people living with HIV.

Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus are important liver flukes that cause a considerable public health burden in eastern Asia, southeastern Asia, and eastern Europe, respectively. The life cycles are complex, involving humans, animal reservoirs, and two kinds of intermediate hosts. An interplay of biological, cultural, ecological, economic, and social factors drives transmission. Chronic infections are associated with liver and biliary complications, most importantly cholangiocarcinoma. With regard to diagnosis, stool microscopy is widely used in epidemiologic surveys and for individual diagnosis. Immunologic techniques are employed for screening purposes, and molecular techniques facilitate species differentiation in reference laboratories. The mainstay of control is preventive chemotherapy with praziquantel, usually combined with behavioral change through information, education and communication, and environmental control. Tribendimidine, a drug registered in the People's Republic of China for soil-transmitted helminth infections, shows potential against both C. sinensis and O. viverrini and, hence, warrants further clinical development. Novel control approaches include fish vaccine and biological control. Considerable advances have been made using multi-omics which may trigger the development of new interventions. Pressing research needs include mapping the current distribution, disentangling the transmission, accurately estimating the disease burden, and developing new diagnostic and treatment tools, which would aid to optimize control and elimination measures.

Glaucoma is a leading cause of irreversible blindness worldwide, caused by the gradual degeneration of retinal ganglion cells and their axons. While glaucoma is primarily considered a genetic and age-related disease, some inflammatory conditions, such as uveitis and viral-induced anterior segment inflammation, cause secondary or uveitic glaucoma. Viruses are predominant ocular pathogens and can impose both acute and chronic pathological insults to the human eye. Many viruses, including herpes simplex virus, varicella-zoster virus, cytomegalovirus, rubella virus, dengue virus, chikungunya virus, Ebola virus, and, more recently, Zika virus (ZIKV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have been associated with sequela of either primary or secondary glaucoma. Epidemiological and clinical studies suggest the association between these viruses and subsequent glaucoma development. Despite this, the ocular manifestation and sequela of viral infections are not well understood. In fact, the association of viruses with glaucoma is considered relatively uncommon in part due to underreporting and/or lack of long-term follow-up studies. In recent years, literature on the pathological spectrum of emerging viral infections, such as ZIKV and SARS-CoV-2, has strengthened this proposition and renewed research activity in this area. Clinical studies from endemic regions as well as laboratory and preclinical investigations demonstrate a strong link between an infectious trigger and development of glaucomatous pathology. In this article, we review the current understanding of the field with a particular focus on viruses and their association with the pathogenesis of glaucoma.

Tuberculosis (TB) is a major global health problem and the second most prevalent infectious killer after COVID-19. It is caused by Mycobacterium tuberculosis (Mtb) and has become increasingly challenging to treat due to drug resistance. The World Health Organization declared TB a global health emergency in 1993. Drug resistance in TB is driven by mutations in the bacterial genome that can be influenced by prolonged drug exposure and poor patient adherence. The development of drug-resistant forms of TB, such as multidrug resistant, extensively drug resistant, and totally drug resistant, poses significant therapeutic challenges. Researchers are exploring new drugs and novel drug delivery systems, such as nanotechnology-based therapies, to combat drug resistance. Nanodrug delivery offers targeted and precise drug delivery, improves treatment efficacy, and reduces adverse effects. Along with nanoscale drug delivery, a new generation of antibiotics with potent therapeutic efficacy, drug repurposing, and new treatment regimens (combinations) that can tackle the problem of drug resistance in a shorter duration could be promising therapies in clinical settings. However, the clinical translation of nanomedicines faces challenges such as safety, large-scale production, regulatory frameworks, and intellectual property issues. In this review, we present the current status, most recent findings, challenges, and limiting barriers to the use of emulsions and nanoparticles against drug-resistant TB.

Strongyloidiasis is a World Health Organization neglected tropical disease usually caused by Strongyloides stercoralis, a parasitic worm with a complex life cycle. Globally, 300-600 million people are infected through contact with fecally contaminated soil. An autoinfective component of the life cycle can lead to chronic infection that may be asymptomatic or cause long-term symptoms, including malnourishment in children. Low larval output can limit the sensitivity of detection in stool, with serology being effective but less sensitive in immunocompromise. Host immunosuppression can trigger catastrophic, fatal hyperinfection/dissemination, where large numbers of larvae pierce the bowel wall and disseminate throughout the organs. Stable disease is effectively treated by single-dose ivermectin, with disease in immunocompromised patients treated with multiple doses. Strategies for management include raising awareness, clarifying zoonotic potential, the development and use of effective diagnostic tests for epidemiological studies and individual diagnosis, and the implementation of treatment programs with research into therapeutic alternatives and medication safety.

The characterization of wild-type minimum inhibitory concentration (MIC) and zone diameter distributions with the setting of epidemiological cut-off values (ECOFFs or ECVs) provides a reference for the otherwise relative MIC values in the international system for antimicrobial susceptibility testing. Distributions of MIC values for a species and an agent follow a log-normal distribution, which in the absence of resistance mechanisms is monomodal and designated wild type (WT). The upper end of the WT distribution, the ECOFF, can be identified with statistical methods. In the presence of phenotypically detectable resistance, the distribution has at least one more mode (the non-WT), but despite this, the WT is most often identifiable using the same methods. The ECOFF provides the most sensitive measure of resistance development in a species against an agent. The WT and non-WT modes are independent of the organism´s response to treatment, but when the European Committee on Antimicrobial Susceptibility Testing (EUCAST) determines the clinical breakpoints, the committee avoids breakpoints that split WT distributions of target species. This is to avoid the poorer reproducibility of susceptibility categorization when breakpoints split major populations but also because the EUCAST has failed to identify different clinical outcomes for isolates with different MIC values inside the wild-type distribution. In laboratory practice, the ECOFF is used to screen for and exclude resistance and allows the comparison of resistance between systems with different breakpoints from different breakpoint organizations, breakpoints evolving over time, and different breakpoints between human and animal medicine. The EUCAST actively encourages colleagues to question MIC distributions as presented on the website (https://www.eucast.org/mic_and_zone_distributions_and_ecoffs) and to contribute MIC and inhibition zone diameter data.

A major impediment for HIV cure is the ability of the virus to integrate its genome in the form of replication-competent proviral DNA into the cellular genome of the host and remain transcriptionally silent and hidden from the host's immune defense mechanisms in latent reservoir cells. These latent reservoirs are highly heterogeneous, long-lived cells that are capable of reactivating to restore the viremic stage in virally suppressed individuals upon treatment interruption, thus necessitating life-long antiretroviral treatment. Latency reversal has become one of the most explored therapeutic approaches for eliminating HIV reservoirs and effecting HIV cure. Various aspects governing the establishment, maintenance, and reversal of HIV latency continue to be an enigma and warrant further research. Quantifying the size of the latent reservoir pool is also a challenge as these cells are very few in number and cannot be easily differentiated from uninfected cells. This article provides a comprehensive review of the in vitro and in vivo models currently available for studying HIV latency as well as the recently developed molecular tools for detection and quantification of latent viral reservoirs.

Invasive fusariosis is a serious invasive fungal disease, affecting immunocompetent and, more frequently, immunocompromised patients. Localized disease is the typical clinical form in immunocompetent patients. Immunocompromised hosts at elevated risk of developing invasive fusariosis are patients with acute leukemia receiving chemotherapeutic regimens for remission induction, and those undergoing allogeneic hematopoietic cell transplant. In this setting, the infection is usually disseminated with positive blood cultures, multiple painful metastatic skin lesions, and lung involvement. Currently available antifungal agents have poor in vitro activity against Fusarium species, but a clear-cut correlation between in vitro activity and clinical effectiveness does not exist. The outcome of invasive fusariosis is largely dependent on the resolution of immunosuppression, especially neutrophil recovery in neutropenic patients.