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The Lancet. HIV Nov 2023The burden of invasive fungal infections associated with opportunistic fungal pathogens is a persistent challenge, particularly among people with advanced HIV disease.... (Review)
Review
The burden of invasive fungal infections associated with opportunistic fungal pathogens is a persistent challenge, particularly among people with advanced HIV disease. In October, 2022, WHO published the Fungal Priority Pathogens List (FPPL)-the first global effort to systematically prioritise fungal pathogens. Of the 19 pathogens in the WHO FPPL, four opportunistic pathogens in particular cause invasive diseases in people living with HIV: Cryptococcus neoformans, Histoplasma spp, Pneumocystis jirovecii, and Talaromyces marneffei. These four fungal pathogens are major causes of illness and death in people with advanced HIV and overwhelmingly affect those in low-income and middle-income countries. Access to diagnostics, improved surveillance, targeted support for innovation, and an enhanced public health focus on these diseases are needed in the effort to reduce HIV-associated deaths.
Topics: Humans; HIV Infections; Histoplasma
PubMed: 37827187
DOI: 10.1016/S2352-3018(23)00174-1 -
Medical Mycology Aug 2023Histoplasma species infect humans and animals, notably bats. Histoplasma species are thermally dimorphic fungi existing in mycelial form in the natural environment and... (Review)
Review
Histoplasma species infect humans and animals, notably bats. Histoplasma species are thermally dimorphic fungi existing in mycelial form in the natural environment and in yeast form in infected tissues. In this narrative literature review, we summarize the occurrence of Histoplasma spp. in different species of bat tissues (n = 49) and in soil admixed with bat guano where the species of bat dwelling nearby has been identified (an additional 18 species likely infected) to provide an up-to-date summary of data. Most positive isolations are from the Americas and Caribbean, with some studies from Thailand, Malaysia, Nigeria, Slovenia, France, and Australia. We also summarize some of the early experimental work to elucidate pathogenicity, latency, immune response, and faecal excretion in bats. Given the recent recognition of the global extent of histoplasmosis, thermal dimorphism in Histoplasma spp., and global heating, additional work on understanding the complex relationship between Histoplasma and bats is desirable.
Topics: Humans; Animals; Histoplasma; Chiroptera; Histoplasmosis; Saccharomyces cerevisiae; Environment
PubMed: 37553137
DOI: 10.1093/mmy/myad080 -
Journal of Fungi (Basel, Switzerland) Feb 2024, the etiological agent for histoplasmosis, is a dimorphic fungus that grows as a mold in the environment and as a yeast in human tissues. It has a broad global... (Review)
Review
, the etiological agent for histoplasmosis, is a dimorphic fungus that grows as a mold in the environment and as a yeast in human tissues. It has a broad global distribution with shifting epidemiology during recent decades. While in immunocompetent individuals infection is usually self-resolving, solid organ transplant recipients are at increased risk of symptomatic disease with dissemination to extrapulmonary tissue. Diagnosis of histoplasmosis relies on direct observation of the pathogen (histopathology, cytopathology, and culture) or detection of antigens, antibodies, or nucleic acids. All transplant recipients with histoplasmosis warrant therapy, though the agent of choice and duration of therapy depends on the severity of disease. In the present article, we describe the pathogenesis, epidemiology, clinical manifestations and management of histoplasmosis in solid organ transplant recipients.
PubMed: 38392796
DOI: 10.3390/jof10020124 -
Infection and Immunity Sep 2023Fungal infections represent a major, albeit neglected, public health threat with serious medical and economic burdens globally. With unacceptably high mortality rates,... (Review)
Review
Fungal infections represent a major, albeit neglected, public health threat with serious medical and economic burdens globally. With unacceptably high mortality rates, invasive fungal pathogens are responsible for millions of deaths each year, with a steadily increasing incidence primarily in immunocompromised individuals. The poor therapeutic options and rise of antifungal drug resistance pose further challenges in controlling these infections. These fungal pathogens have adapted to survive within mammalian hosts and can establish intracellular niches to promote survival within host immune cells. To do that, they have developed diverse methods to circumvent the innate immune system attack. This includes strategies such as altering their morphology, counteracting macrophage antimicrobial action, and metabolic adaptation. This is reminiscent of how bacterial pathogens have adapted to survive within host cells and cause disease. However, relative to the great deal of information available concerning intracellular bacterial pathogenesis, less is known about the mechanisms fungal pathogens employ. Therefore, here we review our current knowledge and recent advances in our understanding of how fungi can evade and persist within host immune cells. This review will focus on the major fungal pathogens, including , and , among others. As we discover and understand the strategies used by these fungi, similarities with their bacterial counterparts are becoming apparent, hence we can use the abundant information from bacteria to guide our studies in fungi. By understanding these strategies, new lines of research will open that can improve the treatments of these devastating fungal diseases.
Topics: Animals; Humans; Mycoses; Candida albicans; Aspergillus fumigatus; Cryptococcosis; Cryptococcus neoformans; Mammals
PubMed: 37506189
DOI: 10.1128/iai.00434-22 -
Journal of Clinical Medicine Jul 2023To summarize the existing knowledge about adrenal gland abscesses, including etiology, clinical presentation, common laboratory and imaging findings, management and... (Review)
Review
To summarize the existing knowledge about adrenal gland abscesses, including etiology, clinical presentation, common laboratory and imaging findings, management and overall morbidity and mortality. Systematic literature review. We performed a search in the PubMed database using search terms: 'abscess and adrenal glands', 'adrenalitis', 'infection and adrenal gland', 'adrenal abscess', 'adrenal infection' and 'infectious adrenalitis'. Articles from 2017 to 2022 were included. We found total of 116 articles, and after applying exclusion criteria, data from 73 articles was included in the final statistical analysis. Of 84 patients included in this review, 68 were male (81%), with a mean age of 55 years (range: 29 to 85 years). Weight loss was the most frequent symptom reported in 58.3% patients, followed by fever in 49%. Mean duration of symptoms was 4.5 months. The most common laboratory findings were low cortisol (51.9%), elevated ACTH (43.2%), hyponatremia (88.2%) and anemia (83.3%). Adrenal cultures were positive in 86.4% cases, with (37.3%) being the leading causative agent. Blood cultures were positive in 30% of patients. The majority of the adrenal infections occurred through secondary dissemination from other infectious foci and abscesses were more commonly bilateral (70%). A total of 46.4% of patients developed long-term adrenal insufficiency requiring treatment. Abscess drainage was performed in 7 patients (8.3%) and adrenalectomy was performed in 18 (21.4%) patients. The survival rate was 92.9%. Multivariate analysis showed that the only independent risk factor for mortality was thrombocytopenia ( = 0.048). Our review shows that adrenal abscesses are usually caused by fungal pathogens, and among these, is the most common. The adrenal glands are usually involved in a bilateral fashion and become infected through dissemination from other primary sources of infection. Long-term adrenal insufficiency develops in 46% of patients, which is more common than what is observed in non-infectious etiology of adrenal gland disorders. Mortality is about 7%, and the presence of thrombocytopenia is associated with worse prognosis. Further prospective studies are needed to better characterize optimal testing and treatment duration in patients with this relatively rare but challenging disorder.
PubMed: 37510716
DOI: 10.3390/jcm12144601 -
Clinical Nephrology. Case Studies 2024Serum anti-neutrophil cytoplasmic antibody (ANCA) positivity with membranoproliferative pattern on renal biopsy can be due to ANCA-associated vasculitis as well as...
Serum anti-neutrophil cytoplasmic antibody (ANCA) positivity with membranoproliferative pattern on renal biopsy can be due to ANCA-associated vasculitis as well as chronic indolent infections. We present the case of an adolescent boy with congenital heart disease and history of cardiac surgery who presented with severe acute kidney injury requiring hemodialysis. Renal biopsy showed membranoproliferative glomerulonephritis with full-house immunofluorescence pattern. Low serum complements, PR3 ANCA positivity and elevated immunoglobulin titers suggested a diagnosis of infective endocarditis-associated glomerulonephritis. Cardiac shunt revision and antibiotic therapy lead to improvement in kidney function. Chronic infections lead to formation of immune complexes that may cause deposit within the renal parenchyma and induce production of ANCA. The distinction of ANCA-associated vasculitis and chronic infections causing acute kidney injury is important in determining therapeutic management. While rare in the pediatric population, we highlight the importance in considering indolent infections in patients with acute glomerulonephritis and ANCA positivity, especially with risk factors.
PubMed: 38222325
DOI: 10.5414/CNCS111233 -
Biomedica : Revista Del Instituto... Aug 2023The existing methods for Paracoccidioides spp. antigen production are problematic in terms of standardization, specificity, stability, repeatability, and reproducibility.
INTRODUCTION
The existing methods for Paracoccidioides spp. antigen production are problematic in terms of standardization, specificity, stability, repeatability, and reproducibility.
OBJECTIVE
To optimize the methodology for Paracoccidioides spp. antigen production and evaluate its applicability in paracoccidioidomycosis immunodiagnosis.
MATERIALS AND METHODS
The antigens were obtained from Paracoccidioides lutzii isolates (01, 66, and 8334), Paracoccidioides brasiliensis sensu stricto (113), and Paracoccidioides restripiensis (B-339). These fungi were grown at 36 °C ± 1 °C, on modified Fava-Netto agar, according to Freitas et al. (2018). Paracoccidioides lutzii antigens were obtained after , 10, and 20 days of culture, whereas P. brasiliensis and P. restripiensis antigens were obtained after 10 days. Antigens were evaluated in natura, 10 and 20 times concentrated. Antigenic capacity was evaluated using a double immunodiffusion assay against serum samples from patients with paracoccidioidomycosis, histoplasmosis, and aspergillosis, and random blood donors.
RESULTS
Cross-reactivity between Paracoccidioides spp. antigens was observed when P. brasiliensis, P. restrepiensis antigens, and P. lutzii antigens were evaluated with the polyclonal antibodies against P. lutzii and P. brasiliensis, respectively. No cross-reactivity was obtained for polyclonal antibodies against Histoplasma capsulatum, Aspergillus fumigatus, and random blood donors. The proposed protocol allowed stable, repeatable, and reproducible genus-specific antigen production at a low cost and in a short cultivation time.
CONCLUSION
The proposed protocol allowed us to obtain genus-specific antigens that can be developed and reproduced in all laboratories in Brazil and South America, where paracoccidioidomycosis is a neglected disease, contributing to an early diagnosis, especially in endemic regions, regardless of the species.
Topics: Humans; Paracoccidioides; Cost-Benefit Analysis; Paracoccidioidomycosis; Reproducibility of Results; Blood Group Antigens; Antibodies
PubMed: 37721912
DOI: 10.7705/biomedica.6874 -
Journal of the Belgian Society of... 2024Due to the mass-like appearance of pulmonary histoplasmosis in the lung, radiological misdiagnosis may occur. Fungal infections should be considered in the differential...
Due to the mass-like appearance of pulmonary histoplasmosis in the lung, radiological misdiagnosis may occur. Fungal infections should be considered in the differential diagnosis, especially in immune-compromised patients.
PubMed: 38680724
DOI: 10.5334/jbsr.3563 -
Clinical Microbiology and Infection :... May 2024Fungal infections are common in HIV-infected individuals and significantly contribute to mortality. However, a substantial number of cases are undiagnosed before death. (Review)
Review
BACKGROUND
Fungal infections are common in HIV-infected individuals and significantly contribute to mortality. However, a substantial number of cases are undiagnosed before death.
OBJECTIVE
To determine the frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa.
METHODS
We conducted a scoping review of autopsy studies conducted in Africa.
DATA SOURCES
PubMed, Scopus, Web of Science, Embase, Google Scholar, and African Journal Online.
STUDY ELIGIBILITY CRITERIA
The review encompasses studies published from inception to September 2023, and no language restrictions were imposed during the search process. We included studies that reported histopathological or microbiological evidence for the diagnosis of fungal infections and other pathogens.
DATA SYNTHESIS
Data were summarized using descriptive statistics and no meta-analysis was performed.
RESULTS
We examined 30 articles reporting studies conducted between 1991 and 2019, encompassing a total of 13 066 HIV-infected decedents across ten African countries. In five studies, the autopsy type was not specified. Among those studies with specified autopsy types, 20 involved complete diagnostic autopsies, whereas 5 were categorized as partial or minimally invasive autopsies. There were 2333 pathogens identified, with 946 (40.5%) being mycobacteria, 856 (36.7%) fungal, 231 (3.8%) viral, 208 (8.9%) parasitic, and 92 (3.9%) bacterial. Of the 856 fungal pathogens identified, 654 (28.0%) were Cryptococcus species, 167 (7.2%) Pneumocystis jirovecii, 16 (0.69%) Histoplasma species, 15 (0.64%) Aspergillus species, and 4 (0.17%) Candida species. Other major non-fungal pathogens identified were cytomegalovirus 172 (7.37%) and Toxoplasma gondii 173 (7.42%).
CONCLUSIONS
Invasive fungal infections occur in over one-third of people who succumb to HIV in Africa. In addition to cryptococcosis and Pneumocystis jirovecii pneumonia, integrating other priority fungal pathogen detection and management strategies into the broader framework of HIV care in Africa is recommended. This involves increasing awareness regarding the impact of fungal infections in advanced HIV disease and strengthening diagnostic and treatment capacity.
Topics: Humans; Autopsy; Africa; HIV Infections; Mycoses; Fungi; AIDS-Related Opportunistic Infections
PubMed: 38145865
DOI: 10.1016/j.cmi.2023.12.016