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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.

Zymosan, an immunogenic cell wall extract of Saccharomyces cerevisiae has potential for use as an experimental pyrogen. However, the short-lived sickness responses noted with intraperitoneal and intra-articular administration of zymosan limits investigations on the long-term effectiveness of antipyretic drugs. Thus, there remains a need to establish an alternative route of zymosan administration that could induce long-lived fevers and inflammation. We injected male Sprague Dawley rats (250–300 g) subcutaneously with zymosan (30 or 300 mg/kg) or saline; n = 7–8. We measured core body temperature, cage activity, food intake and body mass for 24 h after injection. Blood and brain samples were collected at 2, 8, and 18 h after injection. Zymosan (300 mg/kg) induced fever, lethargy, and anorexia, which lasted for 24 h. Zymosan-induced sickness responses were accompanied by increased blood plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α; activation of inflammatory transcription factors (nuclear factor (NF) for IL-6, signal transducer and activator of transcription (STAT)-3, and NF-κB) in the hypothalamus and circumventricular organs; and increased hypothalamic mRNA expression of TNF-α, IL-1β, and IL-6 and rate-limiting enzymes for prostaglandin synthesis. Our results confirm the suitability of subcutaneous administration of zymosan for screening antipyretic and anti-inflammatory drugs in rats.

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.

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.

Brewer’s yeast, derived from the yeast species Saccharomyces cerevisiae (S. cerevisiae), is commonly used for inducing pyrexia in pharmacological studies screening antipyretics in rats. Despite its widespread use, the peripheral and central inflammatory response associated with Brewer’s yeast-induced fever and sickness behavior in rats has not been investigated. Thus, we injected male Sprague-Dawley rats (150–200 g) subcutaneously with a high (4 g/kg, n = 9), medium (2 g/kg, n = 5) or low (0.4 g/kg, n = 6) dose of Brewer’s yeast solution or saline (0.9%, n = 6) and measured core body temperature, cage activity, food intake and body mass for six days after injection. Blood and brain samples were collected at 2, 8, 18 and 72 h after injection; n = 5–7 per time point. Brewer’s yeast administration dose-dependently induced fever, lethargy, anorexia and body mass stunting that was accompanied by increased blood plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and activation of inflammatory transcription factors (nuclear factor (NF) for interleukin-6, signal transducer and activator of transcription (STAT)-3, and NF-κB)) in the hypothalamus and circumventricular organs. The increased activation of transcription factors following Brewer’s yeast administration was accompanied by increased hypothalamic mRNA expression of TNF-α, IL-1β and IL-6 and rate-limiting enzymes for prostaglandin synthesis. Our results show that subcutaneous administration of S. cerevisae induces prolonged fever, anorexia and lethargy that is accompanied by a pronounced increase in the synthesis of pro-inflammatory cytokines, key prostaglandin synthesizing enzymes and transcription factors, in the periphery and brain.

Cryptococcal meningitis is a fatal opportunistic infection of the brain and a leading cause of neurological damage and death in immunocompromised individuals. This neglected fungal disease of the brain is a huge burden on the health systems of developing countries, especially in Sub-Saharan Africa, where up to 25% of people living with HIV/AIDS succumb to it. Cryptococcal fungal cells have a predilection for the brain and they are capable of traversing the blood brain barrier and invade the brain where they cause infection, inflammation and a disruption of normal brain function. A robust host neuroimmune response is critical for pathogen clearance and survival, and a good understanding of the mechanisms underlying its development in the host is critical for the development of effective treatments. However, past basic research studies have been focussed on the characteristics of the fungus and its effect on the peripheral immune system; with little attention paid to how it interacts with brain immune cells. This mini review briefly discusses the paucity of basic research data on the neuroimmune response to cryptococcal infection, raises pertinent questions on how the brain cells respond to the fungal infection, and thereafter discusses models, techniques and advanced technologies that could be useful for carrying out high-throughput research on the pathogenesis of cryptococcal meningitis.

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 (~ 200 g) injected subcutaneously with Brewer's yeast (20 ml/kg of a 20% Brewer's yeast solution = 4000 mg/kg) or saline (20 ml/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 (18 h 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 (5–10 min), peaked at 15–20 min and lasted for 35–50 min. 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.

Oxidative stress is a major contributor of disease aetiology, progression and outcomes. Host systems and parasite infectivity play critical roles in the generation and manipulation of oxidative stress in malaria. Host systems involve the immunological and inflammatory responses that generate free radical species as host signalling processes as well as parasite combating and destructive entities. Parasites trigger molecules with inherent free radical generation in the host. Without the ability to synthesize amino acids, the parasite depends on the breakdown of haemoglobin to salvage the same within the food vacuole. This creates a highly oxidative stress environment from the Fenton reaction through the central ferrous moiety. Elimination of host oxidative stress process, from haemoglobin degradation product haeme, has critically evolved to protect parasites from the hostile intracellular compartment where it is an obligatory inhabitant. Parasites produce antioxidant species from both enzymatic and non-enzymatic molecules which cushions the parasites proteins from oxidation. The parasite also converts haeme, through biocrystallization, to haemozoin, a seemingly biologically inert molecule. In the presence of parasite DNA, haemozoin induces oxidative and inflammatory mediators (cytokines, chemokines, inducible nitric oxide synthase, nitric oxide, oxygen free radical, nitrogen free radicals, peroxynitrite etc.) with a high propensity toward oxidative stress able to override host antioxidant defence systems. Other parasite proponents, e.g. glycosylphosphotidylinositol, are instrumental in negatively modulating host oxidative stress. Without intervention, the disease machineries of oxidative stress go into a vicious cycle of self-propagation mode that leads to host debilitation, cachexia and death. Current drugs are mainly antiparasitic and relieve the “disease” aspect of malaria sparingly. Phytotherapeutics and phytochemicals (asiatic acid, maslinic acid, oleanolic acid), which display anti-oxidant and pro-oxidant properties, have shown both “antiparasite” and “anti-disease” effects promising efficacy in combating malaria. These pleiotropic properties are displayed in different environments with potential to buffer malarial disease syndrome.

We investigated (at the University of the Witwatersrand: GPS coordinates 26°10' 52.96″S; 28°2' 33.61″E) the effects of substituting soya bean meal (SBM) with Ximenia caffra kernel meal (XCKM) as a dietary protein source on blood and liver metabolic substrates content, serum markers of liver and kidney function and the general clinical biochemistry of Sprague Dawley (SD) rats. Five diets with similar energy and protein content were formulated (D1-D5) where XCKM replaced SBM on a crude protein basis at 0, 25, 50, 75 and 100%. Forty weanling male SD rats were randomly assigned to diets D1-D5, fed for 37 days and weighed twice weekly. The rats were then fasted overnight, and fasting blood glucose and triglyceride concentrations were determined from tail-vein-drawn blood. Immediately thereafter, the rats were euthanised and blood was collected via cardiac puncture. Serum was used to assay for markers of the general health profile. Livers were removed and weighed, and samples were used to determine lipid and glycogen content. Rats fed D4 (75% substitution level) had significantly lower (p 0.05) blood triglyceride content compared with rats fed D2 (25% level of substitution). The substitution of SBM with XCKM did not affect (p 0.05) fasting blood glucose and cholesterol concentrations, liver glycogen and lipid content. Additionally, it had no effect (p 0.05) on serum activity/concentration of surrogate markers of liver (alanine aminotransferase and alkaline phosphatase activity and urea, total bilirubin, globulin and albumin concentrations) and kidney (phosphorus, calcium and creatinine concentrations) function and the general clinical biochemistry of the rats. Defatted XCKM could substitute SBM in rat diets without compromising blood glucose and cholesterol homeostasis, liver and kidney function and the general clinical biochemistry of growing male Sprague Dawley rats.

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.

Summary To investigate the progressive effects of a high-fat diet on erythrocyte osmotic fragility, growth performance and serum lipid concentrations in Guinea fowl and Muscovy ducks, 36 Guinea fowl and 36 Muscovy ducks were divided into two groups, for each species, and fed either a standard (STD = commercial poultry feed) or high-fat diet (HFD = commercial poultry feed with 20% palm oil and 2% lard) for up to 12 weeks. After 4, 8 and 12 weeks on the diets, six birds from each group were euthanized and blood samples collected. Osmotic fragility was assessed by measuring the haemoglobin released by erythrocytes placed in serially diluted solutions of phosphate-buffered saline, spectrophotometrically. Serum triglyceride and cholesterol concentrations were also determined. Fragiligrams from erythrocytes from both species of birds on the HFD were not different to those on the STD. However, Muscovy duck erythrocytes were more resistant to haemolysis compared with Guinea fowl erythrocytes. Final body mass and serum triglyceride levels were not significantly different (p > 0.05, anova) between the birds in the HFD and STD groups, for both species of birds. In contrast, serum cholesterol levels were significantly higher in birds on the HFD compared with those on the STD, after 4, 8 and 12 weeks of feeding, for both species of birds. Feeding Guinea fowl and Muscovy ducks a high-fat diet for up to 12 weeks resulted in hypercholesterolaemia but had no effect on final body mass, erythrocyte osmotic fragility or serum triglyceride concentrations in either bird species.

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.

Ficus thonningii is commonly used in traditional medicine across the African continent. Using forty, 6-day old Sprague Dawley rats, we investigated the effects of crude Ficus thonningii extracts on growth, morphology and morphometry of the abdominal viscera, and clinical biochemistry of neonatal rats. The pups were orally gavaged once daily with either low (50 mg.kg-1 b.w), or high (500 mg.kg-1 b.w), doses of aqueous or methanolic F. thonningii leaf extracts while the control received distilled water. After 7, days of treatment, the pups were euthanased and gross morphometric measurements of the abdominal visceral organs were recorded. Samples of the liver, caecum and proximal small intestine were processed for histology. Plasma biochemical parameters were analysed colorimetrically. High methanolic doses of F. thonningii extracts exhibited trophic effects on the stomach while both aqueous and methanolic extracts had trophic effects on the ceacal mucosa of rats. No significant growth-promoting effects were observed in other visceral organs. Histological analysis revealed no mucosal damage or necrosis. Clinical biochemistry parameters were not abnormally altered. There was a significant decrease (p

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.