Antibiotic-resistance in medically important bacteria isolated from commercial herbal medicines in Africa from 2000 to 2021: a systematic review and meta-analysis.

BACKGROUND: Antimicrobial resistance is swiftly increasing all over the world. In Africa, it manifests more in pathogenic bacteria in form of antibiotic resistance (ABR). On this continent, bacterial contamination of commonly used herbal medicine (HM) is on the increase, but information about antimicrobial resistance in these contaminants is limited due to fragmented studies. Here, we analyzed research that characterized ABR in pathogenic bacteria isolated from HM in Africa since 2000; to generate a comprehensive understanding of the drug-resistant bacterial contamination burden in this region. METHODS: The study was conducted according to standards of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). We searched for articles from 12 databases. These were: PubMed, Science Direct, Scifinder scholar, Google scholar, HerbMed, Medline, EMBASE, Cochrane Library, International Pharmaceutical Abstracts, Commonwealth Agricultural Bureau Abstracts, African Journal Online, and Biological Abstracts. Prevalence and ABR traits of bacterial isolates, Cochran's Q test, and the I2 statistic for heterogeneity were evaluated using MedCalcs software. A random-effects model was used to determine the pooled prevalence of ABR traits. The potential sources of heterogeneity were examined through sensitivity analysis, subgroup analysis, and meta-regression at a 95% level of significance. FINDINGS: Eighteen studies met our inclusion criteria. The pooled prevalence of bacterial resistance to at least one conventional drug was 86.51% (95% CI = 61.247-99.357%). The studies were highly heterogeneous (I2 = 99.17%; p < 0.0001), with no evidence of publication bias. The most prevalent multidrug-resistant species was Escherichia coli (24.0%). The most highly resisted drug was Ceftazidime with a pooled prevalence of 95.10% (95% CI = 78.51-99.87%), while the drug-class was 3rd generation cephalosporins; 91.64% (95% CI = 78.64-96.73%). None of the eligible studies tested isolates for Carbapenem resistance. Extended Spectrum ß-lactamase genes were detected in 89 (37.2%) isolates, mostly Salmonella spp., Proteus vulgaris, and K. pneumonia. Resistance plasmids were found in 6 (5.8%) isolates; the heaviest plasmid weighed 23,130 Kilobases, and Proteus vulgaris harbored the majority (n = 5; 83.3%). CONCLUSIONS: Herbal medicines in Africa harbor bacterial contaminants which are highly resistant to conventional medicines. This points to a potential treatment failure when these contaminants are involved in diseases causation. More research on this subject is recommended, to fill the evidence gaps and support the formation of collaborative quality control mechanisms for the herbal medicine industry in Africa.

Distribution of Aspergillus Fungi and Recent Aflatoxin Reports, Health Risks, and Advances in Developments of Biological Mitigation Strategies in China.

Aflatoxins (AFs) are secondary metabolites that represent serious threats to human and animal health. They are mainly produced by strains of the saprophytic fungus Aspergillus flavus, which are abundantly distributed across agricultural commodities. AF contamination is receiving increasing attention by researchers, food producers, and policy makers in China, and several interesting review papers have been published, that mainly focused on occurrences of AFs in agricultural commodities in China. The goal of this review is to provide a wider scale and up-to-date overview of AF occurrences in different agricultural products and of the distribution of A. flavus across different food and feed categories and in Chinese traditional herbal medicines in China, for the period 2000-2020. We also highlight the health impacts of chronic dietary AF exposure, the recent advances in biological AF mitigation strategies in China, and recent Chinese AF standards.

Quality of moxa wool contained in commercial moxibustion devices: test method and examples of waste particle concentration.

BACKGROUND: Moxibustion treatment involves a combination of thermal and chemical stimulation applied by the combustion of moxa wool. The quality of moxa wool is considered to be an important factor in moxibustion treatment traditionally and clinically. However, despite its importance, quantitative and objective methods for determining moxa wool quality are lacking. METHODS: Moxa wool and commercial indirect moxibustion (CIM) device specimens were randomly collected, dried and strained through sieves of various sizes for 10 h. After sieving, the residues remaining on each sieve were collected. The collected samples were weighed and microscopically observed. RESULTS: In this study, we observed that fibres mainly remained on sieves sized 425 µm, and particles were smaller than 300 µm. The residues between 425 and 300 µm varied between the products. In addition, moxa wool for direct moxibustion (DMW) exhibited significantly more fibres than moxa wool for indirect moxibustion (IMW). Most of the CIM devices using moxa wool had a quality similar to IMW, except for one CIM brand using moxa wool that contained three times more waste particles than IMW. CONCLUSION: Based on the results of this study, we conclude that the sieving method is useful for testing the quality of moxa wool even after the CIM manufacturing process. The sieve sizes of 425 and 300 µm could be used as a yardstick to determine the quality of moxa wool. Although this approach requires larger scale validation against existing standard methodologies, we believe it has great potential to be used to improve and safeguard the quality of moxa wool contained in commercial moxibustion devices.

Are over-the-counter fish oil supplements safe, effective and accurate with labelling? Analysis of 10 New Zealand fish oil supplements.

AIM: Fish oil supplements are regulated in New Zealand under the Dietary Supplement Regulations (Section 42, Food Act 1981) and therefore are not subject to the same level of scrutiny and regulations as medicines. We investigated accuracy of labelling, stated health benefits of fish oil supplements sold in New Zealand, and risks relating to possible mercury content. METHOD: The amounts of omega-3 fatty acids contained per capsule were determined by an independent laboratory using gas chromatography on 10 of the most popular over-the-counter fish oil supplements sold in New Zealand and were compared with amounts stated on product labels. Information on doses recommended to achieve a specific health benefit were taken from the 10 labels as well as the company websites. These recommended doses were compared with published recommended doses identified as being effective in those health areas stipulated on the labels, based on either systematic reviews, meta-analyses and/or consensus statements. Mercury was analysed by an independent laboratory using inductively coupled plasma mass spectrometry. RESULTS: The actual amounts of EPA and DHA per capsule in 90% of the over-the-counter fish oil supplements analysed were within 10% of the amount stated on the product labels. Only one product was greater than 10% below the stated dose on the label. All products suggested benefit across heart, brain and joint health and all but two products stated a range of capsules required to achieve that health benefit (eg, 2-6 capsules). Based on the maximum number of capsules recommended (which ranged from 3-6 capsules), only three products would likely confer the dose identified as optimal for achieving a health benefit across all three health areas. Only two products recommended doses that would likely confer a health benefit both at the minimum and maximum number of capsules. More products would likely benefit brain and heart health than joint health. Mercury was not detected in any sample. CONCLUSIONS: It is reassuring that the doses of 90% of the products were accurate and that mercury was not detected in any sample; however, less than a third of the supplements would likely confer all the health benefits stated, even at the highest recommended daily doses. This paper has highlighted the ongoing challenges associated with the regulation of "health claims" associated with dietary supplements in New Zealand. Indeed, the literature on health effects is contradictory at best. Clearer definitions of the types of health statements that can be made and the research necessary to support them requires regulatory clarification.

Bacterial and heavy metal contamination in selected commonly sold herbal medicine in Blantyre, Malawi.

Background: There has been an increase in use of herbal medicine worldwide. It is either used as a stand-alone or complementary therapy to conventional medicine due to past good experience, poverty and family traditions. In Malawi, there are no regulations governing the supply, acquisition, marketing and quality enforcement of herbal medicine. This compromises its safety thereby exposing consumers to avoidable bacteria and heavy metals leading to various adverse health effects. Methods: Cross-sectional laboratory experiments were conducted to determine bacterial and heavy metal contamination of herbal medicine commonly sold in Blantyre, Malawi. A total of 47 samples which were in three formulations namely liquid, powder and tablet were used in the experiments. 29 samples were used for bacterial limit tests and 18 samples were used for heavy metal analysis. Bacterial contamination was determined by streak plate method and biochemical tests while heavy metals were determined by atomic absorption spectroscopy. Descriptive statistics and t-tests were calculated using Microsoft excel and SPSS software programs. Results: Twenty out of the 29 samples (68.9%) were contaminated with Bacillus, coagulase negative Staphylococcus, Klebsiella, Enterobacter, Citrobacter and other-Coliform bacterial species. Most isolated microorganism was Citrobacter spp. (30%), followed by Bacillus spp. (25%). Out of 20 contaminated samples, 75% were contaminated with coliforms. From these 75% which were contaminated with coliforms, 93.3% of them exceeded WHO regulatory limit (103 CFU/g for enterobacteria). Although liquid samples had the highest level of bacterial contaminants, the count was not statistically different from other formulations (P = 0.058). For heavy metals, lead and cadmium were detected and 67% of the samples had lead levels exceeding regulatory limits. Conclusion: Levels of bacterial and lead contamination in herbal medicine from Blantyre markets are far above acceptable limits set by WHO and Canadian guidelines. The use of these herbal medicines is a major risk to the health of consumers.

Fast-switching high-voltage porous-tip electrospray ionization mass spectrometry for rapid detection of antirheumatic drugs in adulterated herbal dietary supplements.

RATIONALE: Herbal dietary supplements (HDSs) adulterated with undeclared synthetic drugs can lead to serious health problems METHODS: A fast-switching positive/negative high-voltage (+/- HV) was developed to apply on electrospray ionization mass spectrometry (ESI-MS) with porous tips for rapid screening of five antirheumatic drugs in antirheumatic HDSs. The fast-switching (switch-time: 100 ms) negative and positive ions were alternately generated to perform full-MS and tandem-MS analysis, providing an effective method for rapid detection of analytes in whichever mode of detection was most suitable (negative or positive ion mode). The use of different tips and solvents was also optimized in this work. RESULTS: The limits of detection of the five antirheumatic drugs were found to be less than 0.1 ng/g (S/N > 3). The reproducibility of the five drugs was measured to be 10.0-23.3% (n = 5). A single sample analysis could be completed within 1 min. Rapid screening of a total of 28 real HDS samples collected from the market was examined by the fast-switching HV substrate-tip ESI-MS method, and the screening result was further validated by conventional liquid chromatography/mass spectrometry. CONCLUSIONS: Overall, our results demonstrated that fast-switching HV substrate-tip ESI-MS is a rapid, reliable, and effective method for simultaneous screening of various analytes in complex samples.

Acute adrenal failure: a potentially fatal consequence of an adulterated herbal remedy.

Herbal remedies adulterated with glucocorticoids can cause Cushing's syndrome. We report a severe presentation of a 'herbal remedy' adulterated with glucocorticoids; causing a potentially fatal adrenal crisis precipitated by acute illness. Investigations were consistent with adrenal suppression and confirmed, after tablet analysis, to be due to a 'herbal remedy' containing synthetic betamethasone/dexamethasone. This case highlights the need for clinical vigilance and patient education about the potential risks associated with the use of unlicensed treatments and the role of tablet analysis in routine biochemistry.

Application of quadrupole-Orbitrap high-resolution mass spectrometry in rapid screening and identification of synthetic dyes in herbal medicines.

In this work, a method combining ultra-high performance liquid chromatography and hybrid quadrupole-Orbitrap high-resolution mass spectrometry (HR-MS) was developed and validated for use in the simultaneous screening, identification, and quantification of 21 synthetic dyes in herbal medicines. To optimize the chromatographic conditions, we used a combined Full mass scan and data-dependent MS/MS (Full MS/dd-MS2) approach in positive and negative ion mode. Under this mode, selected ions with given fragmentation energy were subjected to a dd-MS2 scan following a Full MS scan. The selectivity of this method was effectively improved using 70,000 full width at half maximum mass resolution and narrow mass window (typically 5 ppm), and a single injection was sufficient for simultaneous identification and quantification of 21 synthetic dyes within 10 min. The combined method was fully validated and complies with all criteria for selectivity, sensitivity, calibration curve linearity, accuracy, precision, recovery, matrix effect, and stability. All analytes showed excellent linear relationships as all the coefficients of determination (r2) are greater than 0.9978 over wide ranges of concentrations (e.g. 1.0-500 ng/mL for sunset yellow). The validated method was employed to detect synthetic dyes in herbal medicines and was demonstrated to provide a reliable technical basis for drug regulation and public health protection.

Topical lotions utilized in outpatient rehabilitation clinics as a potential source of bacterial contamination.

Soft tissue mobilization and massage requiring lotions or creams are commonly used interventions in outpatient rehabilitation clinics. For at least 50 years hand creams used in healthcare settings have been found to be contaminated by bacteria. The purpose of this study was to determine the current state of bacterial contamination of lotions used in clinics and to determine the efficacy of lotion preservatives to kill bacteria. Unopened containers of lotions were studied, along with 81 lotion containers used in 22 outpatient clinics in southeast Tennessee and northwest Georgia. Three sites on each container were sampled using sterile swabs. At a microbiology lab, bacterial growth media was inoculated and incubated. Of the 81 containers sampled, 16 supported bacterial growth (19.8%). Container threads displayed the highest contamination compared with other container locations (p < 0.01). No bacteria were found in unopened lotion containers, although when challenged with live bacterial cultures lotion preservatives did not kill bacteria tested. Enrichment cultures using lotions studied here supported the growth of several bacterial species. These findings suggest the need for standardized protocols to help reduce potential healthcare-associated infections due to use of lotions. Improved efficacy of preservatives added to lotions should be a priority.

Heavy Metals in Indigenous Preparations Used for Sex Selection During Pregnancy in India.

Indigenous preparations (IPs) have evoked a considerable interest in alleviating infections and chronic diseases and improving wellbeing. While such formulations have been a part of traditional practice in several countries and many have been reviewed scientifically for their claims, several of them until date remain to be investigated. A class of IPs for sex selection by Indian pregnant women exists with an aim of begetting a male offspring. In view of the leads obtained from our previous studies on detrimental effects of the newborn, for instance stillbirths and congenital malformations, we attempted to investigate the samples for heavy metal toxicity. Three samples were chosen following phytochemical analysis and reproductive toxicity of such preparations under in vivo conditions. The selected samples were examined for heavy metals-lead, cadmium, arsenic, and mercury using Microwave-assisted atomic absorption spectroscopy. The upper limit level of lead, mercury, and cadmium was found to be 18.56, 0.11, and 0.84 mg/kg respectively whereas arsenic was not detected. The levels of lead and mercury were found to be manifolds high in the IP samples that were primarily contributed by its constituents. The results of our study indicate the potential risk conferred upon, to both the mother and fetus on account of high levels of lead, mercury, and cadmium.

Common risks of adulterated and mislabeled herbal preparations.

Due to the growing trend of returning to nature and the fear of adverse reactions from conventional medicines, people are increasingly resorting to the use of herbal preparations. Because of long-term use and natural origin these preparations give a sense of security. But herbal formulations also possess undesirable effects and, among other dangers, present a risk connected with deliberate addition of synthetic compounds, deliberate or unintentional replacement of the plant species or simply a risk of mislabeling. While the replacement of the plant species occurs in a very different groups of herbal products, reports of added illicit synthetic substances often include groups of herbal weight-loss preparations, sexual enhancers, preparations for treatment of rheumatic and inflammatory diseases, antidiabetic and blood pressure lowering preparations. In the world of Internet ordering, these are the dangers that everyone should be aware of. In this article, we reviewed the safety issues related to adulterated or mislabeled herbal products.

Chemical-specific maximum allowable levels for pesticide residues in dietary supplements.

Dietary supplements are regulated by the U.S. FDA as a subset of foods. Most botanical dietary ingredients do not have pesticide tolerances, resulting in the enforcement of zero tolerance or general maximum residue limits (GMRL), rather than utilizing science-informed tolerances. In the current study, chemical-specific maximum allowable levels (MALs) were derived for 185 pesticides by converting existing, authoritative-body human health effects criteria. MALs were derived for 96% of pesticides using criteria established by the U.S. EPA. If multiple authoritative-bodies had established human health effects criteria, the most scientifically-defensible criteria was selected, taking into consideration both carcinogenic and non-carcinogenic endpoints. Five pesticides (o-phenylphenol, pirimicarb, oxadixyl, tetradifon, o,p'-DDT), lacking criteria established by the U.S. EPA had criteria established by other authoritative-bodies that were utilized in the derivation of MALs. Two pesticides did not have any established human health effects criteria (o,p'-DDD and o,p'-DDE). In total, MALs were derived from existing criteria for over 98% of the pesticides in the present study. Consequently, it is demonstrated that human health effects criteria derived by authoritative-bodies can be effectively utilized to derive chemical-specific, science-informed MALs applicable to all food commodities, including botanical ingredients, thereby, minimizing reliance on precautionary zero tolerance and GMRLs.

Occurrence of bacterial and toxic metals contamination in illegal opioid-like drugs in Iran: a significant health challenge in drug abusers.

BACKGROUND: The toxic metals and/or bacterial contaminants in illicit drugs are the main health problems in drug users worldwide. Hence, the potential risks of these contaminants were evaluated in some of the illicit drugs during 2015 and 2016. METHODS: The metals analysis were performed using graphite furnace atomic absorption spectrophotometry. In addition, all microbiological analysis stages, including handling procedures, dilution, and culture media, were conducted in accordance with the US Pharmacopeia (USP) which are harmonized with the European Pharmacopoeia (EP). RESULTS: In the present study, the highest lead (Pb; 138.10 ± 75.01 µg/g) and chromium (Cr; 447.38 ± 20.27 µg/g) levels were detected in opium samples. In addition, the highest prevalence of microbial contamination was observed in opium samples, and the lowest was recorded in heroin samples. Clostridium tetani, with about 50% of contaminant, was the most common bacteria in the analyzed samples. CONCLUSIONS: Our results indicate that Pb exposure as well as bacterial contamination could be the major threats for drug users. Graphical Abstract ᅟ.

Investigation of aflatoxins contamination in herbal materia medica in a Taiwan pharmaceutical factory.

During the years 2005-2016, a total of 1067 samples for 24 types of herbal materia medica were investigated for the presence of aflatoxins (AFs) using immunoaffinity column cleanup and HPLC-coupled to a fluorescence detector after post-column derivatization. AFs were detected in 373 (35%) out of the total samples. Among them, Platycladi Semen (65% for total AFs and 79% for AFB1), Corydalis Rhizoma (53% for total AFs and 32% for AFB1), Corni Fructus (3% for total AFs), Coicis Semen (3% for total AFs and AFB1), Nelumbinis Semen (6% for total AFs and 9% for AFB1), Arecae Semen (18% for AFB1), Polygalae Radix (5% for total AFs and AFB1), and Cassiae Semen (25% for total AFs and 38% for AFB1) exceeded the official limits of 5 and 10 µg/kg, for AFB1 and total AFs (the sum of AFB1, AFB2, AFG1, and AFG2), respectively, set by the Taiwan government. We concluded that Platycladi Semen, Corydalis Rhizoma, and Cassiae Semen are the most commonly contaminated by AFs.

Principal component analysis of synthetic adulterants in herbal supplements advertised as weight loss drugs.

OBJECTIVE: Obesity is one of the major problems in many countries. Herbal drugs are widely used to treat obesity. Unfortunately the majority of herbal weight loss drugs are adulterated with active pharmaceutical ingredients. The purpose of the present study was to analyse herbal weight loss drugs for the general search for pharmaceuticals. METHODS: sixty one herbal weight loss drugs that were collected from herb shops and internet in Kermanshah, Iran were analysed qualitatively using gas chromatography/mass spectrometry. RESULTS: Of the 61 weight loss products sampled, 72% were found to be adulterated with tramadol, caffeine, fluoxetine, rizatriptan, venlafaxine and methadone. CONCLUSION: Herbal weight loss products were adulterated with controlled and legitimate drugs. Patients should be aware of the danger of using adulterated supplements.

Nanoparticle based bio-bar code technology for trace analysis of aflatoxin B1 in Chinese herbs.

A novel and sensitive assay for aflatoxin B1 (AFB1) detection has been developed by using bio-bar code assay (BCA). The method that relies on polyclonal antibodies encoded with DNA modified gold nanoparticle (NP) and monoclonal antibodies modified magnetic microparticle (MMP), and subsequent detection of amplified target in the form of bio-bar code using a fluorescent quantitative polymerase chain reaction (FQ-PCR) detection method. First, NP probes encoded with DNA that was unique to AFB1, MMP probes with monoclonal antibodies that bind AFB1 specifically were prepared. Then, the MMP-AFB1-NP sandwich compounds were acquired, dehybridization of the oligonucleotides on the nanoparticle surface allows the determination of the presence of AFB1 by identifying the oligonucleotide sequence released from the NP through FQ-PCR detection. The bio-bar code techniques system for detecting AFB1 was established, and the sensitivity limit was about 10-8 ng/mL, comparable ELISA assays for detecting the same target, it showed that we can detect AFB1 at low attomolar levels with the bio-bar-code amplification approach. This is also the first demonstration of a bio-bar code type assay for the detection of AFB1 in Chinese herbs.

Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings.

Importance: Over half of adults in the United States report consuming dietary supplements. The US Food and Drug Administration (FDA) has warned of numerous dietary supplements containing undeclared, unapproved pharmaceutical ingredients. These FDA warnings have not been comprehensively analyzed for recent years. Objective: To summarize trends across adulterated (containing unapproved ingredients) dietary supplements associated with a warning released by the FDA from 2007 through 2016. Design, Setting, and Participants: In this quality improvement study, data were extracted from the FDA's Center for Drug Evaluation and Research, Tainted Products Marketed as Dietary Supplements_CDER database from 2007 through 2016. Data from each warning were recorded unless multiple warnings were issued for the same product within a 6-month period. Date, product name, company, hidden ingredient(s), product category, source of sample, and warning document type were recorded for each included warning. Data analysis was conducted from February 2017 to June 2017. Results: From 2007 through 2016, 776 adulterated dietary supplements were identified by the FDA and 146 different dietary supplement companies were implicated. Most of these products were marketed for sexual enhancement (353 [45.5%]), weight loss (317 [40.9%]), or muscle building (92 [11.9%]), with 157 adulterated products (20.2%) containing more than 1 unapproved ingredient. The most common adulterants were sildenafil for sexual enhancement supplements (166 of 353 [47.0%]), sibutramine for weight loss supplements (269 of 317 [84.9%]), and synthetic steroids or steroid-like ingredients for muscle building supplements (82 of 92 [89.1%]). There were 28 products named in 2 or 3 warnings more than 6 months apart. Of these products, 19 (67.9%) were reported to contain new unapproved ingredients in the second or third warning, consistent with the assumption that the FDA found the product to be adulterated more than once. In recent years (2014-2016), 117 of 303 adulterated samples (38.6%) were identified through online sampling and 104 of 303 (34.3%) were identified through the examination of international mail shipments. Conclusions and Relevance: Active pharmaceuticals continue to be identified in dietary supplements, especially those marketed for sexual enhancement or weight loss, even after FDA warnings. The drug ingredients in these dietary supplements have the potential to cause serious adverse health effects owing to accidental misuse, overuse, or interaction with other medications, underlying health conditions, or other pharmaceuticals within the supplement.

Adulteration of proprietary Chinese medicines and health products with undeclared drugs: experience of a tertiary toxicology laboratory in Hong Kong.

AIMS: Proprietary Chinese medicines (pCMs) and health products, generally believed to be natural and safe, are gaining popularity worldwide. However, the safety of pCMs and health products has been severely compromised by the practice of adulteration. The current study aimed to examine the problem of adulteration of pCMs and health products in Hong Kong. METHODS: The present study was conducted in a tertiary referral clinical toxicology laboratory in Hong Kong. All cases involving the use of pCMs or health products, which were subsequently confirmed to contain undeclared adulterants, from 2005 to 2015 were reviewed retrospectively. RESULTS: A total of 404 cases involving the use of 487 adulterated pCMs or health products with a total of 1234 adulterants were identified. The adulterants consisted of approved drugs, banned drugs, drug analogues and animal thyroid tissue. The six most common categories of adulterants detected were nonsteroidal anti-inflammatory drugs (17.7%), anorectics (15.3%), corticosteroids (13.8%), diuretics and laxatives (11.4%), oral antidiabetic agents (10.0%) and erectile dysfunction drugs (6.0%). Sibutramine was the most common adulterant (n = 155). The reported sources of these illicit products included over-the-counter drug stores, the internet and Chinese medicine practitioners. A significant proportion of patients (65.1%) had adverse effects attributable to these illicit products, including 14 severe and two fatal cases. Psychosis, iatrogenic Cushing syndrome and hypoglycaemia were the three most frequently encountered adverse effects. CONCLUSIONS: Adulteration of pCMs and health products with undeclared drugs poses severe health hazards. Public education and effective regulatory measures are essential to address the problem.