Invasive candidiasis encompassing Candida bloodstream infections and deep-seated candidiasis can become a persistent health problem. These infections are caused by Candida species and have high morbidity and mortality rates. Species distribution, access to diagnosis, treatment and mortality are different around the world. The mortality rate is high in South America (30–70%), and Candida albicans is the most prevalent species in this region. However, a global epidemiological shift to non-albicans species has been observed. In this group, C. parapsilosis is the species most frequently detected, followed by C. tropicalis, and at a slower rate, C. glabrata, which has also increased, in addition to the emerging C. auris, resistance to several drugs. This article summarizes relevant aspects of candidemia pathogenesis, such as the mechanisms of fungal invasion, immune response, and the impact of genetic defects that increase host susceptibility to developing the infection. We also discuss relevant aspects of treatment and future challenges in South America.

Antifungal stewardship is a critical component of healthcare management that focuses on optimizing the use of antifungal medications to improve patient outcomes, minimize resistance, and reduce healthcare costs. In resource-limited settings, the prevalence of fungal infections remains a significant health concern, often exacerbated by factors such as compromised immune systems, inadequate diagnostic capabilities, and limited access to antifungal agents. This paper reviews the current state of antifungal stewardship practices in developing countries, addressing the unique socioeconomic and healthcare landscape.

Vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are two forms of a disease caused by Candida spp. β-defensin (BD) is one of the most important families of antimicrobial peptides in the female genital tract and includes molecules that exert essential local functions as antimicrobial and PMN chemoattractant peptides. However, the information on their role during murine and human VVC and RVVC is limited. Thus, we analyzed the behavior and contribution of BD1 to the local response in a VVC mice model and the local cytokine profile and human BD1 and BD3 expression in cervicovaginal lavage from patients with VVC and RVVC. We demonstrated that, in patients with RVVC BD1, mRNA and protein expression were severely diminished and that the aspartate proteinase and lipase secreted by C. albicans are involved in that decrease. This study provides novel information about the pathogenesis of VVC and describes a highly efficient C. albicans escape strategy for perpetuating the infection; these results may contribute to the development of new or combined treatment approaches.

Background: COVID-19 severity has been linked to an increased production of inflammatory mediators called “cytokine storm”. Available data is mainly restricted to the first international outbreak and reports highly variable results. This study compares demographic and clinical features of patients with COVID-19 from Córdoba, Argentina, during the first two waves of the pandemic and analyzes association between comorbidities and disease outcome with the “cytokine storm”, offering added value to the field.Methods: We investigated serum concentration of thirteen soluble mediators, including cytokines and chemokines, in hospitalized patients with moderate and severe COVID-19, without previous rheumatic and autoimmune diseases, from the central region of Argentina during the first and second infection waves. Samples from healthy controls were also assayed. Clinical and biochemical parameters were collected.Results: Comparison between the two first COVID-19 waves in Argentina highlighted that patients recruited during the second wave were younger and showed less concurrent comorbidities than those from the first outbreak. We also recognized particularities in the signatures of systemic cytokines and chemokines in patients from both infection waves. We determined that concurrent pre-existing comorbidities did not have contribution to serum concentration of systemic cytokines and chemokines in COVID-19 patients. We also identified immunological and biochemical parameters associated to inflammation which can be used as prognostic markers. Thus, IL-6 concentration, C reactive protein level and platelet count allowed to discriminate between death and discharge in patients hospitalized with severe COVID-19 only during the first but not the second wave.Conclusions: Our data provide information that deepens our understanding of COVID-19 pathogenesis linking demographic features of a COVID-19 cohort with cytokines and chemokines systemic concentration, presence of comorbidities and different disease outcomes. Altogether, our findings provide information not only at local level by delineating inflammatory/anti-inflammatory response of patients but also at international level addressing the impact of comorbidities and the infection wave in the variability of cytokine and chemokine production upon SARS-CoV-2 infection.

This work examines cellular immunity against SARS-CoV-2 in patients from Córdoba, Argentina, during two major waves characterized by different circulating viral variants and different social behavior. Using flow cytometry, we evaluated the main lymphocyte populations of peripheral blood from hospitalized patients with moderate and severe COVID-19 disease. Our results show disturbances in the cellular immune compartment, as previously reported in different cohorts worldwide. We observed an increased frequency of B cells and a significant decrease in the frequency of CD3⁺ T cells in COVID-19 patients compared to healthy donors (HD). We also found a reduction in Tregs, which was more pronounced in severe patients. During the first wave, the frequency of GZMB, CD107a, CD39, and PD-1-expressing conventional CD4⁺ T (T conv) cells was significantly higher in moderate and severe patients than in HD. During the second wave, only the GZMB⁺ T conv cells of moderate and severe patients increased significantly. In addition, these patients showed a decreased frequency in IL-2-producing T conv cells. Interestingly, we identified two subsets of circulating CD8⁺ T cells with low and high CD8 surface expression in both HD and COVID-19 patients. While the percentages of CD8^hi and CD8^lo T cells within the CD8⁺ population in HD are similar, a significant increase was observed in CD8^lo T cell frequency in COVID-19 patients. CD8^lo T cell populations from HD as well as from SARS-CoV-2 infected patients exhibited lower frequencies of the effector cytokine-producing cells, TNF, IL-2, and IFN-γ, than CD8^hi T cells. Interestingly, the frequency of CD8^lo T cells increased with disease severity, suggesting that this parameter could be a potential marker for disease progression. Indeed, the CD8^hi/CD8^lo index helped to significantly improve the patient’s clinical stratification and disease outcome prediction. Our data support the addition of, at least, a CD8^hi/CD8^lo index into the panel of biomarkers commonly used in clinical labs, since its determination may be a useful tool with impact on the therapeutic management of the patients.

Vulvovaginal candidiasis (VVC) is a mucosal infection predominantly caused by Candida albicans, affecting over three-quarters of immunocompetent women worldwide. While the female genital tract mucosa is the primary defense against the fungus, the specific immune mechanisms involved in this host-pathogen interaction remain largely unknown. In this study, we explored the relevance of type-I interferons (IFNs-I) pathway using both in vitro and in vivo models of VVC. Our quantitative proteomic analysis revealed that C. albicans induces the activation of the IFNs-I pathway in human epithelial cells (ECs) of the female genital tract shortly after exposure to the fungus. Additionally, we identified β-glucans as a crucial fungal component involved in triggering this pathway. Using a VVC model in IFN-α/β receptor-deficient (Ifnar1-/-) mice, we demonstrated that IFNs-I regulate the fungal burden, C. albicans epithelial invasion, polymorphonuclear neutrophils (PMNs) recruitment, inflammatory tissue response, local cytokine balance, and the composition of T cell subsets in the draining lymph nodes. These findings underscore the pivotal role of the IFNs-I pathway in ECs-mediated responses against C. albicans, especially in the early stages of VVC development, offering insights into potential therapeutic targets for this condition.