A desktop review of evaluation of implementation of national medicines policies in SADC countries.

A national medicine policy (NMP), formerly referred to as a national drug policy (NDP) is a document that serves as a political commitment and guide for action by the government to provide safe, efficacious, quality assured, available, affordable and rationally used medicines. This is the first study to review the implemented components of the NMPs of the 16 South African Development Community (SADC) countries over the past ten years (2011-2021). Information published between 2011 and 2021 of each country such as pharmaceutical profiles, official government documents, WHO/HAI/World Bank datasets and research studies on the implemented components were appraised. Significant progress has been made by 16 SADC countries over the period 2011-2021 in implementing the NMP. The most commonly implemented components included the concept of essential medicines, pricing, and regulation. Though traditional and herbal medicines component is yet to be implemented by the majority. The pharmacist-patient ratio of 1:2300 was below the target for all countries, prompting the need to strengthen the pharmacy personnel in the healthcare systems. Medicine pricing, affordability, and availability studies are necessary to develop equitable pricing policies that will improve the accessibility of medicines in all countries and the SADC region. With the exception of the Republic of Tanzania, SADC countries need to urgently revise their NMPs, thus adopting progressive processes such as incorporating Health Technology Assessment (HTA) in the NMP. All SADC countries require a strong, internationalistic evaluation culture built-in their policy formulation. As the first study to investigate the implemented NMPs in the SADC region, it could serve as a springboard for the countries to address their common pharmaceutical challenges thus improving their readiness for universal health coverage (UHC). Future in-depth cross-country studies in the SADC region are necessary to comprehensively evaluate the implemented components of NMPs.

Analysis of Aflatoxin Biomarkers in the Hair of Experimental Animals.

Analysis of body fluids and tissues of aflatoxin exposed individuals for the presence of aflatoxins and aflatoxin metabolites has emerged as a reliable indicator of exposure and metabolism of aflatoxins. However, current aflatoxin biomarkers are not appropriate for investigating the long-term effects of aflatoxin exposure. In this explorative study, we investigated the analysis of hair as a complementary or alternative matrix for the assessment of biomarkers of long-term aflatoxin exposure. Three groups of guinea pigs were orally dosed with 5 ugkg-1bw-1, 50 ugkg-1bw-1, and 100 ugkg-1bw-1 of AFB1. Urine and hair samples were collected on days 0, 1, 2, 3, 7, 30, 60, and 90 and analysed for AFB1 and AFM1 using UHPLC-MS/MS. AFB1 and AFM1 were detected in 75% and 13.6%, respectively, of the day 1 to day 7 urine samples. AFB1 was detected in hair samples collected from day 3 up to day 60. This is the first report to confirm the deposition of AFB1 in the hair of experimental animals. These findings indicate that hair analysis has the potential to provide an accurate long-term historical record of aflatoxin exposure with potentially important implications for the field of aflatoxin biomarkers.

Checklist of African Soapy Saponin-Rich Plants for Possible Use in Communities' Response to Global Pandemics.

Plants that exhibit foaming properties when agitated in aqueous solutions are commonly referred to as soapy plants, and they are used in different communities for washing, bathing, and hair shampooing. The frothing ability of these plants is attributed to saponins which are also well-documented to possess antimicrobial attributes. In the light of COVID-19, soap and hand hygiene have taken center stage. The pandemic has also revealed the low access to running water and commercial soaps in many marginalized and poor communities to the detriment of global health. Thus, soapy plants, either in their natural form or through incorporation in commercial products, may be a relevant additional weapon to assist communities to improve hand hygiene and contribute to curbing COVID-19 and other communicable infections. This review paper was compiled from a review of literature that was published between 1980 and 2020. We found 68 plant species, including those which are already used as traditional soaps. Our findings support the potential use of extracts from soapy plants because of their putative viricidal, bactericidal, and fungicidal activities for use in crude home-based formulations and possibly for developing natural commercial soap products.

Scientists' Warning on Climate Change and Medicinal Plants.

The recent publication of a World Scientists' Warning to Humanity highlighted the fact that climate change, absent strenuous mitigation or adaptation efforts, will have profound negative effects for humanity and other species, affecting numerous aspects of life. In this paper, we call attention to one of these aspects, the effects of climate change on medicinal plants. These plants provide many benefits for human health, particularly in communities where Western medicine is unavailable. As for other species, their populations may be threatened by changing temperature and precipitation regimes, disruption of commensal relationships, and increases in pests and pathogens, combined with anthropogenic habitat fragmentation that impedes migration. Additionally, medicinal species are often harvested unsustainably, and this combination of pressures may push many populations to extinction. A second issue is that some species may respond to increased environmental stresses not only with declines in biomass production but with changes in chemical content, potentially affecting quality or even safety of medicinal products. We therefore recommend actions including conservation and local cultivation of valued plants, sustainability training for harvesters and certification of commercial material, preservation of traditional knowledge, and programs to monitor raw material quality in addition to, of course, efforts to mitigate climate change.

Drug Quality in South Africa: A Field Test.

To assess drug quality and pharmaceutical care in South Africa, "mystery" (i.e., anonymous) customers collected 316 samples from July to September 2016. Solid dosage forms containing amoxicillin alone or in combination with clavulanic acid as well as analgesics containing paracetamol alone or in combination with other drugs were sampled in a randomized fashion from the formal market (pharmacies) and by convenient sampling from the informal market. Visual inspection, uniformity of dosage units, and dissolution testing were performed to evaluate adherence to pharmacopoeial quality standards and to identify counterfeit, degraded, or substandard drugs. Although no counterfeited products were identified, only 55.4% (173/312) of samples were able to fulfill all pharmacopeial requirements for quality. Most of the 139 samples that failed were unable to pass the visual inspection due to inappropriate labeling and packaging. In addition, several substandard products were identified: 17 (5.4%) samples failed dissolution testing and 15 (4.8%) failed the content uniformity test. To improve drug quality and the quality of pharmaceutical care, better education of pharmaceutical professionals and monitoring of the pharmaceutical supply chain in South Africa are needed. Further field studies are necessary to evaluate risks and quality issues for other drug classes and distribution channels.

The mutagenic and antimutagenic activity of Sutherlandia frutescens extracts and marker compounds.

BACKGROUND: Sutherlandia frutescens (L.) R. Br is endemic to Southern Africa where it has been traditionally used for cancer and diabetes. In recent times it has been marketed for its reputed (but not proven) anticancer, antidiabetic and anti-HIV properties. Little is known about the mutagenic and antimutagenic potential of extracts and common marker compounds of Sutherlandia frutescens. Therefore this study aimed to investigate the putative efficacy and possible long-term adverse effects of using this herb. METHODS: Ethylacetate (EA) and 50% Methanol (MeOH) extracts were screened for mutagenic and antimutagenic activity using the Ames assay utilising TA97a, TA98, TA100 and TA102 in the presence and absence of metabolic activation. Four compounds, L-arginine, L-canavanine, GABA and D-pinitol known to occur in sutherlandia were also included. The total polyphenolic content of the both extracts was determined using the Folin-Ciocalteau method and FRAP and ABTS were used to determine the anti-oxidant potential of the extracts. RESULTS: The extracts and the standards did not show any cytotoxicity except in TA97a. The EA extract exhibited antimutagenicity against all the bacterial strains at all concentrations tested. The MeOH extract showed both pro-mutagenic and antimutagenic activities with 2-acetamidofluorene and aflatoxin B1 in the presence of metabolic activation of TA98 and TA100, respectively. All compounds, except L-canavanine exhibited antimutagenic activity against all strains. L-canavanine, on the other hand showed co-mutagenicity with 9-aminoacridine on TA97a, at all test concentrations. The extracts and pure compounds exhibited their antimutagenic activity in a dose response manner. L-arginine and GABA showed an some antimutagenic response. EA extract had three times the total phenolic content (12.56 µg GE / mg) observed in the MeOH extract. There was correlation between total phenolic content, antioxidant potential and antimutagenicity. CONCLUSION: Both extracts exhibited a protective effect, with the EA extract exhibiting greater potency. L-canavanine acted as a co-mutagen in a dose response manner without metabolic activation. It is suggested that the EA extract be priotized for future development work as it showed a better risk profile and activity.

Peanuts, Aflatoxins and Undernutrition in Children in Sub-Saharan Africa.

Peanuts (Arachis hypogaea) is an important and affordable source of protein in most of Sub-Saharan Africa (SSA) and a popular commodity and raw material for peanut butter, paste and cooking oil. It is a popular ingredient for foods used at the point of weaning infants from mother's milk. It is at this critical point that childhood undernutrition occurs and the condition manifests as stunting, wasting and growth restriction and accounts for nearly half of all deaths in children under five years of age in SSA. Undernutrition is multi-factorial but weaning foods contaminated with microbiological agents (bacteria and fungi) and natural toxins have been shown to play a big part. While peanuts may provide good nutrition, they are also highly prone to contamination with mycotoxigenic fungi. The high nutritive value of peanuts makes them a perfect substrate for fungal growth and potential aflatoxin contamination. Aflatoxins are highly carcinogenic and mutagenic mycotoxins. This article reviews the nutritional value and aflatoxin contamination of peanuts, the role they play in the development of childhood malnutrition (including the different theories of aetiology) and immunological problems in children. We also discuss the control strategies that have been explored and advocacy work currently taking shape in Africa to create more awareness of aflatoxins and thus combat their occurrence with the goal of reducing exposure and enhancing trade and food safety.

Aflatoxin biomarkers in hair may facilitate long-term exposure studies.

Aflatoxins are highly toxic fungal metabolites produced by some members of the Aspergillus species. They are low molecular weight lipophilic compounds that are easily absorbed from the gastrointestinal tract. They contaminate most staple foods, including maize, peanuts, peanut butter and sorghum mainly in the tropics where hot and humid conditions promote fungal growth. Absorbed aflatoxins are metabolized by the cytochrome P450 enzyme system in the liver into toxic metabolites. Aflatoxin B (AFB)1 is the most toxic, carcinogenic and mutagenic naturally occurring toxin. Aflatoxin exposure assessment has been traditionally achieved through food use frequency questionnaires and laboratory analysis of food samples. However, estimation of individual exposure to aflatoxins based on these methods may not be accurate. The use of aflatoxin biomarkers in urine and blood for use in exposure studies has emerged in more recent times. However, the current biomarkers (e.g., AFB-N7 -guanine and AFB1 -albumin adduct) in use have a short half-life and are only practically useful to indicate levels over 24 h-3 months post-exposure. There is therefore an immediate need to study and evaluate alternative biomarkers in non-conventional matrices such as hair and nails. Hair analysis revealed considerable interest in forensic analysis particularly in the detection of drugs of abuse where it has emerged as a sensitive and specific technique complementary to blood and urinalysis. This article provides an overview of aflatoxins, current aflatoxin biomarkers and proposes the use of hair as a potential matrix for biomarkers of long-term aflatoxin exposure. Copyright © 2016 John Wiley & Sons, Ltd.

Mycological and aflatoxin contamination of peanuts sold at markets in Kinshasa, Democratic Republic of Congo, and Pretoria, South Africa.

Peanut (Arachis hypogaea L.) is an important food crop in sub-Saharan Africa. In this survey, the mycological and aflatoxin contamination of peanuts collected from Kinshasa, Democratic Republic of Congo, and Pretoria, South Africa, was assessed. Twenty peanut samples were purchased randomly at informal markets in the two cities and analysed for mycoflora and aflatoxins (AFB1, AFB2, AFG1 and AFG2) using standard methods. The results indicated that 95% of the Kinshasa samples and 100% of the Pretoria samples were contaminated with aflatoxigenic fungi in the ranges 20-49,000 and 40-21,000 CFU/g, respectively. Seventy-five per cent of the Kinshasa samples and 35% of the Pretoria samples exceeded the maximum limits of AFB1 as set by The Joint FAO/WHO Expert Committee on Food Additives. Residents of both cities are at a high risk of aflatoxin exposure despite their apparent cultural, socio-economic, geographic and climatic differences. Further work needs to be done to understand the supply chains of peanut trade in informal markets of the two countries so that interventions are well targeted on a regional rather than a national level.

Phytochemical and antimicrobial investigations of stilbenoids and flavonoids isolated from three species of Combretaceae.

The antimicrobial activity and chemistry of the African Combretaceae has been well studied in recent years. The present study aimed to investigate the phytochemistry and antimicrobial activity of lesser known members of this family viz. C. hereroense, C. apiculatum and C. collinum. Pulverized leaves of C. collinum and C. apiculatum, and the fruit of C. hereroense were extracted with organic solvents and subjected to preparative chromatography. Seventeen phenolic constituents including four phenanthrenes from the fruit of C. hereroense and two known bibenzyls (including a combretastatin) from the leaves of C. collinum were isolated. The compounds were then subsequently tested for their antimicrobial activity against Candida albicans, Mycobacterium fortuitum, Staphylococcus aureus, Escherichia coli and Proteus vulgaris. Pinocembrin showed excellent activity against C. albicans (MIC - 6.25 µg/ml), superior to that of the positive control, fluconazole and against S. aureus (MIC - 12.5 mg/ml). The phenanthrenes (compounds 1, 2, 3 and 5) showed some activity against M. fortuitum and S. aureus with a uniform MIC of 25 µg/ml. From this study it was evident that most stilbenoids and flavonoids from the selected Combretaceae have little or no antimicrobial activity.

Determination of aflatoxin in processed dried cassava root: validation of a new analytical method for cassava flour.

A new method that uses HPLC with a photochemical reactor for enhanced detection was developed and validated for the determination of aflatoxins in cassava flour. Samples were spiked with a mixture of four aflatoxins at 5, 10, and 20 microg/kg mixed with either 1 or 5 g NaCI and extracted with methanol-water (80 + 20, v/v) by shaking for 10 or 30 min. An immunoaffinity column was used for cleanup. HPLC with postcolumn derivatization, for enhancement of aflatoxin fluorescence, and fluorescence determination were used for quantitation of the toxin concentration. The method was validated for recovery, linearity, and precision at the three concentrations tested. Recovery ranges were 52-70, 69-85, and 80-89% for the spiking levels of 5.0, 10.0, and 20.0 microg/kg, respectively. It appears that the amount of salt (NaCl) and the shaking time are critical factors in this method; optimal performance was obtained when 1 g salt was used and the shaking time was 10 min. The good linearity and precision of the method allowed baseline separation from interferences, e.g., coumarins.

Preliminary exposure assessment of deoxynivalenol and patulin in South Africa.

Deoxynivalenol (DON) and patulin (PAT) are mycotoxins widely regulated internationally. DON is frequently found in cereals, whereas PAT is commonly found in apple juices. A survey of South African commercial products was conducted on DON levels in maize meal and wheat flours, and on PAT levels in apple juices. DON levels in 23 wheat flour samples (mean of 16 positives, 29 µg/kg) were equal to or below 100 µg/kg and in wheat consumers contributed 6-13% of the provisional maximum tolerable daily intake (PMTDI; 1 µg/kg body weight per day) for DON set by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Sixteen of 18 maize meal samples were contaminated, with a mean for positive samples of 294 µg/kg, and the probable daily intakes ranged from 3.67 µg/kg body weight per day in rural infants to 1.39 µg/kg body weight per day in urban adults. PAT levels in 20 of 30 apple-juice samples were below the detection level of 10 µg/l. Mean of positive samples was 210 µg/l, with three samples exceeding the South African legal limit of 50 µg/l and the highest level (1,650 µg/l) showing the possibility of a brief but high exposure of 37 µg/kg body weight per day (or 9,250% of the JECFA PMTDI of 0.4 µg/kg body weight per day) in young children.

Phytochemical and antifungal studies on Terminalia mollis and Terminalia brachystemma.

Phytochemical investigation of the stem bark of Terminalia mollis afforded friedelin (1), catechin with epicatechin (2), gallocatechin with epigallocatechin (3) and 3-O-methylellagic acid 4'-O-alpha-rhamnopyranoside (4). Arjunolic acid with 2alpha, 3beta, 23-trihydroxy-urs-12-en-28-oic acid (5), 2alpha-hydroxyursolic acid (6), gallic acid (7), chebulanin (8) and 2''-O-galloylvitexin (9) were isolated from the leaf. Chebulanin (8), betulinic acid (10), ursolic acid (11), catechin (12), isoorientin (13), orientin (14), isovitexin (15) and punicalagin (16) were isolated from Terminalia brachystemma leaf. The first full unambiguous NMR assignments for (4) and (8), and revised assignments for (9), are reported. Compound (16) showed good activity against three Candida species.

Colorimetric broth microdilution method for the antifungal screening of plant extracts against yeasts.

Screening plant extracts for antifungal activity is increasing due to demand for new antifungal agents, but the testing methods present many challenges. Standard broth microdilution methods for antifungal susceptibility testing of available antifungal agents are available now, but these methods are optimised for single compounds instead of crude plant extracts. In this study we evaluated the standard NCCLS method as well as a modification which uses spectrophotometric determination of the end-points with a plate reader. We also evaluated another standard method, the EUCAST method, which is a similar microdilution assay to the NCCLS method, but uses a larger inoculum size and a higher glucose concentration in the medium as well as spectrophotometric end-point determination. The results showed that all three methods had some drawbacks for testing plant extracts and thus we modified the NCCLS broth microdilution method by including a colorimetric indicator-resazurin for end-point determination. This modified method showed good reproducibility and clear-cut end-point, plus the end-point determination needed no instruments. It enabled us to evaluate the activity of a selection of extracts from six Combretaceous plants against three Candida spp. and thus provided pharmacological evidence for some traditional uses of these plants while assisting the identification of the active ingredients.

Determination of patulin in apple juice: comparative evaluation of four analytical methods.

The performance of 4 purification methods for the analysis of patulin in apple juice was evaluated by high-performance liquid chromatography (HPLC). Samples were spiked with patulin at 10, 20, 50, 100, and 150 ppb (ng/mL) and extracted by one of 4 methods (3 solid-phase extraction and one liquid-liquid extraction), and then analyzed by HPLC-UV under the same isocratic conditions. The methods were validated for recovery, linearity, and precision at high and low concentrations. Recoveries were all >70% for spiking range 10-150 ppb. The relative standard deviation for repeatability was found to meet European Union Directive requirements. In addition, all the methods showed baseline separation from hydroxymethylfurfural.

Do fumonisin mycotoxins occur in wheat?

The fumonisin mycotoxins are mainly produced by the fungi Fusarium verticillioides and Fusarium proliferatum, which are both field pathogens of maize. The natural occurrence of fumonisins has been verified in maize and a large range of maize-based products in many countries of the world. However, occasional reports have emerged of fumonisins being detected in wheat, despite the main producing fungi not being pathogens of this cereal. An investigation was conducted into a recent report of the natural occurrence of fumonisins in the 2003/2004 South African wheat crop at levels up to 1.7 mg/kg, as determined by immunoaffinity column cleanup and direct fluorometric measurement. An AOAC International high-performance liquid chromatographic (HPLC) method for the determination of fumonisins in maize was modified and validated for the determination of fumonisins in spiked wheat samples. HPLC analysis of the wheat samples previously found to be positive for fumonisins revealed no detectable (<5 microg/kg) fumonisins in the 30 samples analyzed. These results, which lay doubt on previous reports of fumonisins in wheat, emphasize the fact that screening methods, especially if used outside their range or matrix of applicability, can produce false positive results despite the use of immunoaffinity cleanup. Such results should be validated and confirmed with a more definitive technique.

Antibacterial and antioxidant activity of Sutherlandia frutescens (Fabaceae), a reputed anti-HIV/AIDS phytomedicine.

Dried ground leaves of Sutherlandia frutescens were extracted by both sequential extraction with four solvents, starting with the least polar and separately with acetone, ethanol and water. The extracts were tested for antibacterial and antioxidant activity. The hexane extract was, generally, the most active extract against S. aureus, E. faecalis and E. coli with MIC values of 0.31, 1.25 and 2.50 mg/mL, respectively. The second method extracted compounds with antioxidant activity as shown by the DPPH free-radical scavenging assay. The use of Sutherlandia frutescens for topical staphylococcal infections, when formulated in an oily base appears to have a rational basis.

Cyclobutanes from Combretum albopunctatum.

A dichloromethane extract of the aerial parts of Combretum albopunctatum Suesseng afforded five phenolic compounds-three known flavonoids and two novel cyclobutane chalcone dimers. The chemical structures were determined by standard spectroscopic techniques and the structure and relative stereochemistry of one chalcone dimer, rel-(1 alpha,2 beta)-di-(2,6-dimethoxy-4-hydroxy)-benzoyl-rel-(3 alpha,4 beta)-diphenylcyclobutane, were confirmed by single crystal X-ray diffraction.