Search

Human fungal infections are a historically neglected area of disease research, yet they cause more than 1.5 million deaths every year. Our understanding of the pathophysiology of these infections has increased considerably over the past decade, through major insights into both the host and pathogen factors that contribute to the phenotype and severity of these diseases. Recent studies are revealing multiple mechanisms by which fungi modify and manipulate the host, escape immune surveillance and generate complex comorbidities. Although the emergence of fungal strains that are less susceptible to antifungal drugs or that rapidly evolve drug resistance is posing new threats, greater understanding of immune mechanisms and host susceptibility factors is beginning to offer novel immunotherapeutic options for the future. In this Review, we provide a broad and comprehensive overview of the pathobiology of human fungal infections, focusing specifically on pathogens that can cause invasive life-threatening infections, highlighting recent discoveries from the pathogen, host and clinical perspectives. We conclude by discussing key future challenges including antifungal drug resistance, the emergence of new pathogens and new developments in modern medicine that are promoting susceptibility to infection., (© 2024. Springer Nature Limited.)

Pneumocystis jirovecii is a major fungal pathogen of humans that causes life-threatening lung infections in immunocompromised individuals. Despite its huge global impact upon human health, our understanding of the pathobiology of this deadly fungus remains extremely limited, largely because it is not yet possible to cultivate Pneumocystis in vitro, independently of the host. However, a recent paper by Munyonho et al. offers a major step forward (F. T. Munyonho, R. D. Clark, D. Lin, M. S. Khatun, et al., 2023, mBio 15:e01464-23, https://doi.org/10.1128/mbio.01464-23). They show that it is possible to maintain both the trophozoite and cyst forms of the mouse pathogen, Pneumocystis murina, in precision-cut lung slices for several weeks. Furthermore, they demonstrate that this offers the exciting opportunity to examine potential virulence factors such as possible biofilm formation as well as antifungal drug responses in the lung., Competing Interests: The authors declare no conflict of interest.

Cryptococcal immune reconstitution inflammatory syndrome (C-IRIS) is a condition that affects immunosuppressed individuals recruited to antiretroviral therapy. In a recent publication, Kawano and colleagues used a mouse model to demonstrate that pulmonary dysfunction, one of the fatal complications of C-IRIS, is caused by T cell-driven neurodegeneration in a vital medullary nucleus of the brain responsible for respiratory control., Competing Interests: Declaration of interests The authors declare no competing interests in relation to this work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The emergence of deadly fungal infections in Africa is primarily driven by a disproportionately high burden of human immunodeficiency virus (HIV) infections, lack of access to quality health care, and the unavailability of effective antifungal drugs. Immunocompromised people in Africa are therefore at high risk of infection from opportunistic fungal pathogens such as Cryptococcus neoformans and Pneumocystis jirovecii, which are associated with high morbidity, mortality, and related socioeconomic impacts. Other emerging fungal threats include Emergomyces spp., Histoplasma spp., Blastomyces spp., and healthcare-associated multi-drug resistant Candida auris. Socioeconomic development and the Covid-19 pandemic may influence shifts in epidemiology of invasive fungal diseases on the continent. This review discusses the epidemiology, clinical manifestations, and current management strategies available for these emerging fungal diseases in Africa. We also discuss gaps in knowledge, policy, and research to inform future efforts at managing these fungal threats., (© 2022 The Authors. Parasite Immunology published by John Wiley & Sons Ltd.)

Cryptococcal meningitis affects millions of people worldwide and is especially prevalent in regions with a high burden of HIV/AIDS. The study of the pathophysiology of this often fatal disease has been significantly hindered by the lack of reliable experimental models, especially at the level of the brain, which is the main organ of injury. Here we outline our novel protocol for the use of hippocampal organotypic brain slice cultures (HOCs) to study the host-fungal interactions during cryptococcal infections of the brain. HOCs are a powerful platform for investigating neuroimmune interactions as they allow for the preservation of all innate neuroglial cells including microglia, astrocytes, and neurons, all of which maintain their three-dimensional architecture and functional connectivity. We made HOCs from neonatal mice and infected these with a fluorescent strain of Cryptococcus neoformans for 24 h. Using immunofluorescent staining, we confirmed the presence and morphology of microglia, astrocytes, and neurons in HOCs prior to infection. Using fluorescent and light microscopy, we also confirmed that Cryptococcus neoformans encapsulates and buds in vitro, as it would in a host. Finally, we demonstrate that infection of HOCs with Cryptococcus neoformans results in close association of the fungal cells with host microglial cells. Our results demonstrate the utility of HOCs as a model to study the pathophysiology and host neuroimmune responses in neurocryptococcosis, which may assist in improving our collective understanding of the pathogenesis of this disease., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Overconsumption of fructose time dependently induces the development of non-alcoholic fatty liver disease (NAFLD). We investigated whether ursolic acid (UA) intake by new-born rats would protect against fructose-induced NAFLD. One hundred and seven male and female Sprague Dawley rat pups were randomly grouped and gavaged (10 ml/kg body weight) with either 0.5% dimethylsulphoxide (vehicle control), 0.05% UA, 50% fructose mixed with UA (0.05%) or 50% fructose alone, from postnatal day 6 (P6) to P20. Post-weaning (P21-P69), the rats received normal rat chow (NRC) and water to drink. On P70, the rats in each group were continued on water or 20% fructose to drink, as a secondary high fructose diet during adulthood. After 8 weeks, body mass, food and fluid intake, circulating metabolites, visceral adiposity, surrogate markers of liver function and indices of NAFLD were determined. Food intake was reduced as a result of fructose feeding in both male and female rats (p < 0.0001). Fructose consumption in adulthood significantly increased fluid intake and visceral adiposity in female rats (p < 0.05) and had no apparent effects in male rats (p > 0.05). In both sexes of rats, fructose had no significant (p > 0.05) effects on body mass, circulating metabolites, total calorie intake and surrogate markers of hepatic function. Fructose consumption in both early life and adulthood in female rats promoted hepatic lipid accumulation (p < 0.001), hypertrophy, microvesicular and macrovesicular steatosis (p < 0.05). Early-life UA intake significantly (p < 0.001) reduced fructose-induced hepatic lipid accumulation in both male and female rats. Administration of UA during periods of developmental plasticity shows prophylactic potential against dietary fructose-induced NAFLD.

Metabolic syndrome (MetS) is a prevalent, multifactorial and complex disease that is associated with an increased risk of developing diabetes and other major cardiovascular complications. The rise in the global prevalence of MetS has been attributed to genetic, epigenetic, and environmental factors. The adoption of sedentary lifestyles that are characterized by low physical activity and the consumption of high-energy diets contributes to MetS development. Current management criteria for MetS risk factors involve changes in lifestyle and the use of pharmacological agents that target specific biochemical pathways involved in the metabolism of nutrients. Pharmaceutical drugs are usually expensive and are associated with several undesirable side effects. Alternative management strategies of MetS risk factors involve the use of medicinal plants that are considered to have multiple therapeutic targets and are easily accessible. Medicinal plants contain several different biologically active compounds that provide health benefits. The impact of phytochemicals present in local medicinal plants on sustainable health and well-being of individuals has been studied for many years and found to involve a plethora of complex biochemical, metabolic, and physiological mechanisms. While some of these phytochemicals are the basis of mainstream prescribed drugs (e.g., metformin, reserpine, quinine, and salicin), there is a need to identify more medicinal plants that can be used for the management of components of MetS and to describe their possible mechanisms of action. In this review, we assess the potential health benefits of South African ethnomedicinal plants in protecting against the development of health outcomes associated with MetS. We aim to provide the state of the current knowledge on the use of medicinal plants and their therapeutically important phytochemicals by discussing the current trends, with critical examples from recent primary references of how medicinal plants are being used in South African rural and urban communities.

Background and Objective: The sub-saharan livestock feed industry depends on imported soyabean meal (SBM) as a dietary protein source in feeds thus making livestock production costly. This calls for the search and development of local dietary protein sources. Using Sprague Dawley rats to model monogastric animals, this study evaluated the potential of Ximenia caffra kernel meal (XCKM) to substitute SBM as a dietary protein source in feeds., Materials and Methods: Five diets were formulated wherein XCKM replaced SBM on a crude protein basis at 0, 25, 50, 75 and 100%. In the digestibility trial, 20 adult male SD rats were randomly assigned to the 5 diets. After a 12-day adaptation period feed and nutrient intake, faeces and urine output were determined over a 5-day collection period. Apparent Total Tract Digestibility (ATTD) of nutrients and nitrogen absorption and retention were determined. In the growth trial, 40 weanling male SD rats were randomly assigned to the five dietary treatments and fed for 38 days. The rats were weighed twice weekly. Following euthanasia, gastrointestinal viscera were harvested and their macro-morphometry determined. Linear growth was determined from tibiae and femora indices., Results: In adult rats dietary XCKM had no (p>0.05) effect on ATTD of nutrients. At 100% substitution of SBM, XCKM increased (p<0.05) faecal nitrogen loss while at 75% substitution level it increased (p<0.05) nitrogen retention. In growing SD rats, although dietary XCKM had no effect (p>0.05) on the terminal body and empty carcass mass and viscera macro-morphometry, at 100% SBM substitution, it significantly compromised (p<0.05) body mass gain and average daily gain. Femora and tibiae mass and seed or index significantly decreased (p<0.05) with increased dietary XCKM., Conclusion: The XCKM could replace SBM as a dietary protein source in adult SD rat feeds without compromising ATTD digestibility of nutrients and nitrogen utilization thus it could be speculated that XCKM can be utilized as a dietary protein source in feeds of mature monogastrics. Caution must be exercised in using XCKM in grower rat diets as its use at higher inclusion levels compromised growth performance and long bone health.

Stress-induced hyperthermia following rectal thermometry is reported in normothermic rats, but appears to be muted or even absent in febrile rats. We therefore investigated whether the use of rectal thermometry affects the accuracy of temperature responses recorded in normothermic and febrile rats. Using intra-abdominally implanted temperature-sensitive radiotelemeters we measured the temperature response to rectal temperature measurement in male Sprague Dawley rats (~200g) injected subcutaneously with Brewer's yeast (20ml/kg of a 20% Brewer's yeast solution=4000mg/kg) or saline (20ml/kg of 0.9% saline). Rats had been pre-exposed to, or were naive to rectal temperature measurement before the injection. The first rectal temperature measurement was taken in the plateau phase of the fever (18h after injection) and at hourly intervals thereafter. In normothermic rats, rectal temperature measurement was associated with an increase in abdominal temperature (0.66±0.27°C) that had a rapid onset (5-10min), peaked at 15-20min and lasted for 35-50min. The hyperthermic response to rectal temperature measurement was absent in febrile rats. Exposure to rectal temperature measurement on two previous occasions did not reduce the hyperthermia. There was a significant positive linear association between temperatures recorded using the two methods, but the agreement interval identified that rectal temperature measured with a thermocouple probe could either be 0.7°C greater or 0.5°C lower than abdominal temperature measured with radiotelemeter. Thus, due to stress-induced hyperthermia, rectal thermometry does not ensure accurate recording of body temperature in short-spaced, intermittent intervals in normothermic and febrile rats., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The fatty acid composition of the underutilised Cassia abbreviata seed oil was determined using gas chromatographic methods. C. abbreviata seeds yielded 9.53% of yellowish-green oil consisting mainly of oleic acid (37.8%), palmitic acid (26.5%), linoleic acid (26.7%), stearic acid (4.1%) and elaidic acid (2.1%). The oil was solid at room temperature, had a saponification value of 376.16 mg KOH/g and an iodine value of 26.48 g I2/100g oil. The fatty acid composition and saponification value of the C. abbreviata seed oil suggest that it may find application in both cosmetic and pharmaceutical natural product formulations.

Aloe ferox is an important medicinal plant in Southern Africa whose seeds could be useful as a source of oil. The fatty acid composition of A. ferox seed oil was determined using gas chromatography. The physicochemical properties of the oil were analysed using standard methods. The seeds yielded 19.4% of a light textured oil using the Blight and Dyer's method and 12.3% using the Soxhlet extraction method. The saponification value of the seed oil was 241.9 mg KOH/g and the peroxide value was 8.9 meq/kg. The acid value of the seed oil was 51.5 mg KOH/g (25.9% free fatty acids). The major fatty acids found in the seed oil were linoleic acid (71.8%), oleic acid (12.0%), palmitic acid (11.2%) and stearic acid (2.9%). The results obtained suggest that as A. ferox seed oil is high in linoleic acid, it could be potentially exploited in the cosmetic and pharmaceutical industries.

The common wild fig, Ficus thonningii, is extensively used in African ethnomedicine for treating a number of disease conditions which include diarrhoea, urinary tract infections, diabetes mellitus, gonorrhoea, respiratory infections, and mental illnesses. This review aims to present a logical analysis of the nutritional, phytochemical and pharmacological properties of F. thonningii in relation to its therapeutic applications. A bibliographic analysis of the uses, phytochemical constituents and phytophamacological properties of Ficus thonningii was carried out using published papers, medicinal plant databases and various ethnobotanical and ethnopharmacological books. Ficus thonningii contains various bioactive compounds which include alkaloids, terpenoids, flavonoids, tannins and active proteins, all of which contribute to its curative properties. In vitro and in vivo pharmacological studies revealed that F. thonningii possesses antimicrobial, antidiarrhoeal, antihelmintic, antioxidant, anti-inflammatory and analgesic properties. Acute and sub-chronic toxicity studies have shown that Ficus thonningii is non-toxic if administered orally in low doses. Scientific research has validated the ethnomedicinal claims that Ficus thonningii is useful in disease management. However, there is need to continue identifying, isolating and quantifying the active principles and possibly determine the mechanisms underlying its curative properties.