Current topics in microbiology and immunology最新文献

COVID-19 convalescent plasma (CCP) is an important therapeutic option for immunocompromised patients with COVID-19. Such patients are at increased risk for serious complications of infection and may also develop a unique syndrome of persistent infection. This article reviews the rationale for CCP utilization in immunocompromised patients and the evidence for its value in immunosuppressed patients with both acute and persistent COVID-19. Both historical precedence and understanding of the mechanisms of action of antibody treatment support this use, as do several lines of evidence derived from case series, comparative studies, randomized trials, and systematic reviews of the literature. A summary of recommendations from multiple practice guidelines is also provided.

In recent years, several types of novel fungal health problems have been emerging in parallel. Antifungal-drug-resistant opportunistic pathogens have emerged both in previously unknown lineages, notably Candida auris, and in traditional pathogens and opportunists such as the Trichophyton mentagrophytes species complex and Aspergillus fumigatus. Emergence of resistance in Aspergillus is clearly connected to agricultural use of fungicides related to medical antifungals, but is brought into further prominence by the simultaneous emergence of immunosuppressive viral effects connected to influenza and SARS CoV 2 infections. The sources of drug resistance phenotypes in Candida auris and Trichophyton indotineae are unclear, but neither climate change nor drug misuse can be clearly implicated. In Onygenalean endemic mycoses, however, climate change is under suspicion of causing range extension in Coccidioides immitis. Decimation of some North American bat species associated with Histoplasma hot spots has not had a perceptible effect on this fungus so far. Historical reading suggests that it may have survived a previous loss of conditioned habitat when the passenger pigeon became extinct. Emergence of Emergomyces and new Blastomyces species appears mainly to be related to enhanced recognition. Two separate sporotrichosis outbreaks in cats in South America and Southeast Asia suggest a little-discussed mechanism of pathogen emergence, opportunity trawling, i.e. ingress of new potential hosts into pathogen habitats leading to novel epizootics. In the investigations of non-pathogenic fungi connected to immunologically or toxicologically mediated symptomatology in indoor environments, the slow augmentation of difficult-to-obtain evidence has clarified that indoor dampness and mould can cause diverse health effects, ranging from novel advent of asthmatic conditions to eczema-like skin disturbances. The methodology used to evaluate indoor mould symptomatology shares some of the deficiencies that racked medical evaluations of causality during the SARS CoV 2 outbreak. Pertinent epidemiological connections may be obscured by an excessive positivistic demand for proof where the combination of valid evidence and judicious attention to the precautionary principle would better serve the community.

This autobiographical account chronicles a lifelong battle with fungal infections and lung disease, beginning with childhood exposure to damp, mouldy environments in flood-prone homes. The author recounts recurring lung collapses as a teenager, culminating in multiple pleurectomies and a diagnosis of blebs on the pleural lining. Years later, persistent symptoms and a series of lung infections led to a diagnosis of chronic pulmonary aspergillosis (CPA) and severe bronchiectasis, traced to prolonged mould exposure. This chapter details the challenges of managing these conditions, including antifungal treatments, side effects, emergency surgeries, and lifestyle adjustments. The story underscores the importance of self-advocacy, collaboration with medical and mycology experts, and leveraging reliable online resources to better understand and manage chronic diseases. The author offers actionable strategies for others facing similar health challenges, emphasizing proactive care and resilience in the face of adversity. This inspiring journey highlights the intersection of personal perseverance and medical innovation in overcoming the long-term impacts of fungal lung disease.

During the global health emergency caused by the coronavirus disease 2019 (COVID-19), evidence relating to the efficacy of convalescent plasma therapy-evidence critically needed for both public policy and clinical practice-came from multiple levels of the epistemic hierarchy. The challenges of conducting clinical research during a pandemic, combined with the biological complexities of convalescent plasma treatment, required the use of observational data to fully assess the impact of convalescent plasma therapy on COVID symptomatology, hospitalization rates, and mortality rates. Observational studies showing the mortality benefits of convalescent plasma emerged early during the COVID-19 pandemic from multiple continents and were substantiated by real-time pragmatic meta-analyses. Although many randomized clinical trials (RCTs) were initiated at the onset of the pandemic and were designed to provide high-quality evidence, the relative inflexibility in the design of clinical trials meant that findings generally lagged behind other forms of emerging information and ultimately provided inconsistent results on the efficacy of COVID-19 convalescent plasma. In the pandemic framework, it is necessary to emphasize more flexible analytic strategies in clinical trials, including secondary, subgroup, and exploratory analyses. We conclude that in totality, observational studies and clinical trials taken together provide strong evidence of a mortality benefit conferred by COVID-19 convalescent plasma, while acknowledging that some randomized clinical trials examined suboptimal uses of convalescent plasma.

Blood transfusion capacity in low- and middle-income countries (LMICs), encompassing both the safety and adequacy of the blood supply, is limited. The challenges facing blood banks in LMICs include regulatory oversight, blood donor selection, collection procedures, laboratory testing, and post-transfusion surveillance. A high proportion of LMICs are unable to fully meet clinical demands for blood products, and many do not meet even the minimum threshold of collection (10 units per 1000 population). Suboptimal clinical transfusion practices, in large part due to a lack of training in transfusion medicine, contribute to blood wastage. During the COVID-19 pandemic, high- and LMICs alike experienced blood shortages, in large part due to quarantine and containment measures that impeded donor mobility. COVID-19 convalescent plasma (CCP) was particularly appealing for the treatment of patients with COVID-19 in LMICs, as it is a relatively inexpensive intervention and makes use of the existing blood collection infrastructure. Nonetheless, the challenges of using CCP in LMICs need to be contextualized among broad concerns surrounding blood safety and availability. Specifically, reliance on first time, family replacement and paid donors, coupled with deficient infectious disease testing and quality oversight, increase the risk of transfusion transmitted infections from CCP in LMICs. Furthermore, many LMICs are unable to meet general transfusion needs; therefore, CCP collection also risked exacerbation of pervasive blood shortages.

Fungi are essential for a wide variety of food products and processes. They have a major role in the production of many fermented foodstuffs, may be eaten directly as fruit bodies and mycelium, and are used to produce food additives. They contribute to food production worldwide, even in cultures which do not typically consume mushrooms, because yeasts and edible moulds are utilised in a great variety of fermentation processes. Most fungal cultures used in food production at industrial scale show evidence of selection and domestication. However, other strains may still be obtained from the wild, either through incidental colonisation of a fermentation substrate as a result of a traditional preparation method or due to the inability to reliably cultivate a given organism, necessitating collection from its native habitat. This review provides an overview of the uses of fungi, both yeasts and filamentous fungi, in food production with a focus on research findings over the past decade. This includes a review of the production of foodstuffs through the fermentation of a wide variety of substrates, particularly dairy, but also including meat and plant matter. In addition, the use of fungi in the production of secreted enzymes and food additives is considered. Finally, the cultivation and harvesting of fungal fruiting bodies and mycoprotein are reviewed. The review aims to capture the breadth of the field by covering examples from every inhabited continent, including reference to fungal food systems which have historically been under-studied.

Donor-recipient proximity emerged as an important factor influencing the efficacy of COVID-19 convalescent plasma (CCP) treatment during the early stages of the COVID-19 pandemic. This relationship was uncovered while analyzing data collected in the collaborative Expanded Access Program (EAP) for CCP at Mayo Clinic, a project aimed to establish protocols for CCP use amid the uncertainty of the novel disease. Analysis of data from nearly 28,000 patients revealed a significant reduction in risk of 30-day mortality for those receiving near-sourced plasma when compared to those receiving distantly sourced plasma [pooled relative risk, 0.73 (95% CI 0.67-0.80)], prompting adjustments in treatment protocols at selected institutions, and highlighting the importance of proximity in optimizing CCP outcomes. Despite its significance, subsequent studies of CCP effectiveness in COVID-19 have often overlooked donor-recipient proximity. Our findings emphasize the importance of donor-recipient proximity in CCP treatment in the current pandemic, and we discuss potential methods for improving CCP efficacy in future pandemics. Our recommendations include prioritizing virus genotyping for vulnerable patients, establishing a robust testing infrastructure, and collecting additional donor data to enhance plasma selection. This chapter underscores the importance of comprehensive data collection and sharing to navigate the evolving landscape of newly emerging infectious diseases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept across the world in the waning months of 2019 and emerged as the cause of the coronavirus disease 19 (COVID-19) pandemic in early 2020. The use of convalescent plasma (CP) for prior respiratory pandemics provided a strong biological rationale for the rapid deployment of COVID-19 convalescent plasma (CCP) in early 2020 when no validated treatments or prior immunity existed. CCP is an antiviral agent, with its activity against SARS-CoV-2 stemming from specific antibodies elicited by the virus. Early efforts to investigate the efficacy of CCP in randomized clinical trials (RCTs) that targeted hospitalized patients with COVID-19 did not demonstrate the overall efficacy of CCP despite signals of benefit in certain subgroups, such as those treated earlier in disease. In contrast, studies adhering to the principles of antibody therapy in their study design, choice of patient population, and product qualification, i.e., those that administered high levels of specific antibody during the viral phase of disease in immunocompromised or very early in immunocompetent individuals, demonstrated benefits. In this chapter, we leverage the knowledge gained from clinical studies of CCP for COVID-19 to propose a framework for future studies of CP for a new infectious disease. This framework includes obtaining high-quality CP and designing clinical studies that adhere to the principles of antibody therapy to generate a robust evidence base for using CP.

In contrast to therapy in oncology and immune-related diseases, where dozens of monoclonal antibodies (mAbs) have been introduced, often in transformative fashion, the use of mAbs for infectious diseases is generally underdeveloped, with fewer than a dozen mAbs currently licensed for the treatment of microbial diseases. This situation is paradoxical given that antibodies are major products of the immune system for protecting against infectious diseases. The underdevelopment of mAbs for infectious diseases has several causes including the availability of effective therapy against many microbial diseases, the fact that many pathogenic microbes are antigenically diverse and thus all strains are not covered by a single mAb, and the high expense of mAb therapies. Despite these hurdles the number of mAbs licensed for infectious disease indications is slowly increasing and there are numerous opportunities for the development of mAbs in the prevention and treatment of microbial diseases.

The use of the serum or plasma of patients or animals who have recovered from an infectious disease, or had been immunized with a relevant antigen, to treat or prevent the same infection in others began in the late 1880s when French and German scientists uncovered, one step at a time, several of the elements of the immune system's response to infection. A key finding was that the damage caused by some bacteria depends upon their secreted toxins which can be neutralized by biologic agents. Antitoxins to diphtheria and tetanus began to be manufactured in large animals in France, Germany, and the US in the 1890s and were soon being used worldwide. The impact of diphtheria antitoxin on childhood mortality was profound. Shortly after the development of antitoxins, convalescent serum began to be used for its anti-bactericidal properties thus addressing serious infections caused by non-toxin-producing organisms. The effectiveness of antitoxins and antisera was demonstrated by examining mortality rates in hospitals before and after the introduction of antitoxins, by comparisons of treated and untreated patients, by comparing early and late treatment and dosage, by examining vital data mortality trends, and by several randomized and alternate assignment trials. Antitoxins continue to have a role in the rare cases of diphtheria and other conditions largely eradicated by immunization, but serum therapy nearly disappeared from the medical armamentarium with the development of antibiotics in the 1940s. Inasmuch as new human pathogens are now emerging with unprecedented regularity as seen in the recent COVID-19 pandemic, and because specific therapies are unlikely to be available for them, plasma-based antibody therapies are likely to again carve out a niche in infectious disease control.