Traditional herbal medicine regulatory implementation in Ethiopia: a qualitative study.

Background: Approximately 80% of the Ethiopian population predominantly depends on herbal medicines (HMs) for their primary healthcare needs. Nevertheless, worries regarding the safety, efficacy, and standard of herbal-based treatments have been escalating due to the lack of strong regulatory frameworks. Therefore, the study aimed to assess the presence of regulatory frameworks for traditional herbal medicines and their enforcement in Ethiopia. Methods: The qualitative-phenomenological study design was conducted from November 2021 to March 2022 G.C. The study included 25 regulatory official key informants (KIs) who work for national and regional medicine regulatory agencies, and 15 traditional herbal medicine (THM) practitioners who work at the regional level were purposefully selected for an in-depth interview (IDI). An in-depth interview guide was developed through the purposive sampling technique. The collected data were analyzed using thematic content analysis techniques. Results: The study found that the current national medicine proclamation is deemed inadequate in the regulation of THM. Both conventional and traditional herbal medicines are regulated by a single agency. Weak legal enforcement, a lack of government commitment and support, resource constraints, and inadequate regulatory tools are the main challenges faced in THM regulation. Conclusion: Overall, the study found inadequate legal frameworks and weak THM regulatory implementations in Ethiopia. Consequently, it is critical for all regulatory authorities in Ethiopia to exert their utmost efforts to effectively regulate THM.

Assessment of the extent and monetary loss in the selected public hospitals in Jimma Zone, Ethiopia: expired medicine perspectives.

Introduction: Medicine plays a crucial role in the field of healthcare as a therapeutically significant pharmaceutical product. By effectively preventing diseases, medicine has the power to save countless lives and improve the quality of life for people worldwide. However, despite hospitals' efforts to provide medical care to patients, a significant issue arises from the substantial amount of drugs that go unused due to expiration dates. This problem is particularly prevalent in resource-limited countries like Ethiopia, where the pharmaceutical supply system fails to adequately address the issue of expired drugs in public hospitals, leading to an unsatisfactory situation. Hence, the objective of this study was to assess the economic impact and volume of expired medicines in the selected public hospitals in Jimma Zone, Southwestern Ethiopia. Methods: A hospital-based cross-sectional study design was conducted to assess the economic impact and volume of expired medicines available in the public hospitals in Jimma Zone. All available hospitals that fulfilled the EFDA guidelines were included. The medication expiration rate was calculated by dividing the total monetary value of expired medicines in a year by the total value of medicines received in the same year multiplied by 100. Then, the collected data was cleared, filtered, coded, and quantitatively analyzed using the Microsoft Excel 2010 version. Results: The average medicine waste rate was 4.87% in the fiscal year of 2019/2020 and 2020/2021 in Jimma Zone public hospitals worth 32,453.3 US$. Additionally, the facility wasted an estimated of 2711.44 US$ on the disposal of expired medicines. The expiration of medicines has been linked to several issues, including near-expiry, irrational prescribing practices, and weak participation of clinicians in medicine selection and quantification of the facility. Additionally, only two hospitals had relatively good storage and handling practices. Conclusion: Overall, the expiration rate of medicines in the public hospitals in Jimma Zone was greater than the allowed level of 2%. In order to optimize the allocation of healthcare funds and ensure the appropriate use of pharmacologically significant medications it is vital to conduct a comprehensive examination at the national level within a regional hospitals.

In-vitro susceptibility and ex-vivo evaluation of macrocyclic lactone endectocides sub-lethal concentrations against Plasmodium vivax oocyst development in Anopheles arabiensis.

BACKGROUND: Asymptomatic malaria transmission has become a public health concern across malaria-endemic Africa including Ethiopia. Specifically, Plasmodium vivax is more efficient at transmitting earlier in the infection and at lower densities than Plasmodium falciparum. Consequently, a greater proportion of individuals infected with P. vivax can transmit without detectable gametocytaemia. Mass treatment of livestock with macrocyclic lactones (MLs), e.g., ivermectin and doramectin, was suggested as a complementary malaria vector tool because of their insecticidal effects. However, the effects of MLs on P. vivax in Anopheles arabiensis has not yet been fully explored. Hence, comparative in-vitro susceptibility and ex-vivo studies were conducted to evaluate the effects of ivermectin, doramectin and moxidectin sub-lethal concentrations on P. vivax oocyst development in An. arabiensis. METHODS: The 7-day sub-lethal concentrations of 25% (LC25) and 5% (LC5) were determined from in-vitro susceptibility tests on female An. arabiensis in Hemotek® membrane feeding assay. Next, an ex-vivo study was conducted using P. vivax gametocytes infected patient's blood spiked with the LC25 and LC5 of the MLs. At 7-days post-feeding, each mosquito was dissected under a dissection stereo microscope, stained with 0.5% (w/v) mercurochrome solution, and examined for the presence of P. vivax oocysts. Statistical analysis was based on a generalized mixed model with binomially distributed error terms. RESULTS: A 7-day lethal concentration of 25% (LC25, in ng/mL) of 7.1 (95% CI: [6.3;8.0]), 20.0 (95%CI:[17.8;22.5]) and 794.3 (95%CI:[716.4;1516.3]) were obtained for ivermectin, doramectin and moxidectin, respectively. Similarly, a lethal concentration of 5% (LC5, in ng/mL) of 0.6 (95% CI: [0.5;0.7]), 1.8 (95% CI:[1.6;2.0]) and 53.7 (95% CI:[ 48.4;102.5]) were obtained respectively for ivermectin, doramectin and moxidectin. The oocyst prevalence in treatment and control groups did not differ significantly (p > 0.05) from each other. Therefore, no direct effect of ML endectocides on P. vivax infection in An. arabiensis mosquitoes was observed at the sub-lethal concentration (LC25 and LC5). CONCLUSIONS: The effects of ivermectin and doramectin on malaria parasite is more likely via indirect effects, particularly by reducing the vectors lifespan and causing mortality before completing the parasite's sporogony cycle or reducing their vector capacity as it affects the locomotor activity of the mosquito.

Substandard and falsified antimicrobials in selected east African countries: A systematic review.

BACKGROUND: Globally, millions of people have been affected by fraudulent pharmaceutical products, particularly those in developing countries. Although the problem of falsified and substandard drugs is acknowledged, the extent of the issue is ever-changing, has a dynamic nature, and should be quantified and captured in a recent snapshot. OBJECTIVE: This systematic review seeks to examine the data that can quantify and provide a current snapshot of the prevalence of SF antimicrobials in selected east Africa countries. METHODS: Scientific studies on antimicrobial quality were searched in PubMed, Embase, Scopus, and Google Scholar from 2017 to February 2023. The search strategy focused on scientific articles published in peer-reviewed scientific journals written in English and the studies exclusively done in any of the selected countries of east Africa. The articles were carefully reviewed by two individuals for inclusion independently, first by title followed by abstract and the full-text retrieval. To minimize bias associated with the methodology used for data collection, the quality of the studies was assessed for quality according to the Medicine Quality Assessment Reporting Guidelines (MEDQUARG). The reporting of this systematic review was done following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). RESULTS: Fifteen studies that estimated the prevalence of poor-quality antimicrobial medicines in selected four east African countries were included. The overall percentage of samples of antimicrobials that failed at least one quality test was 22.6% (151/669) with each class's prevalence of 17% in antibiotics (73/432), 24% in antimalarial (41/171), and 56% in anthelmintics (37/66). Quality control parameters of API content were the most commonly examined in the included studies, accounting for 14/15 (93%) studies. Fifty (33.1%) of the failing samples failed assay API- content determination, while 26.5% (n = 40) failed the visual inspection and packaging analysis; 19.2% (29) failed dissolution; 14% (n = 21) flawed hardness or friability; 4%(n = 6) failed uniformity, as well as 3.2% (n = 5) failed disintegration test of the quality control parameter. CONCLUSION: It was found that this review was general in these selected east African countries and was a catalyst for combating the menace of poor-quality medications that affect millions of lives.

Prevalence and Determinants of Geohelminthiasis among School-Age Children in Jimma City, Ethiopia.

School-age children (SAC) are at a higher risk of geohelminth or soil-transmitted helminth (STH) infections due to their practice of walking and playing barefoot, lack of adequate sanitary facilities, and poor personal hygiene. In Ethiopia, periodic deworming has been implemented since 2013 with the aim of interrupting the transmission of STH in children by 2025. To evaluate the likely success of such a control program, it is crucial to monitor the transmission of STH, especially in peri-urban settings where environmental sanitation is modest. The aim of this study was to determine the prevalence and determinants of STH infections among SAC in peri-urban areas of Jimma City, Southwestern Ethiopia. A community-based cross-sectional study was conducted in five peri-urban Kebeles of Jimma City from July to September, 2021. Systematic random sampling was used to select 522 households with at least one child, and 478 children (5-15 years old) were recruited randomly from the households. Data on sociodemographic and potential risk factors were collected using a structured questionnaire. Stool samples from each study participant were collected and examined microscopically using the Kato-Katz technique. Multivariate logistic regression model was used to identify risk factors associated with STH infections. The prevalence of any STH among SAC was 23.4%, with Ascaris lumbricoides being the predominant STH species (15.7%), followed by Trichuris trichiura (9%) and hookworm (2.1%). Most (86.6%) of the STH-positive SAC had a single infection and a light infection intensity (88.2%), with a mean intensity of 367.4 eggs per gram. Location of Kebele (AOR = 2.73; 95% CI: 1.21-6.16, p=0.016), lack of hand washing after defecation (AOR = 6.39; 95% CI: 3.16-12.95, p < 0.001), untrimmed fingernails (AOR = 2.65; 95% CI: 1.56-4.51, p < 0.001), and lack of previous deworming (AOR = 2.90; 95% CI: 1.47-5.74, p=0.002) were significant predictors for STH infections among SAC. In conclusion, the study revealed that STH infections are significant health problem in the peri-urban areas of Jimma City. Strengthening periodic deworming and improving children's hygiene through health education are required to reduce the transmission.

Pharmacokinetics of macrocyclic lactone endectocides in indigenous Zebu cattle and their insecticidal efficacy on Anopheles arabiensis.

Outdoor biting, outdoor resting, and early evening biting of Anopheles arabiensis is a challenge in current malaria control and elimination efforts in Africa. Zooprophylaxis using livestock treated with macrocyclic lactones is a novel approach to control zoophilic vectors. Therefore, the present study aimed to investigate the pharmacokinetics and insecticidal efficacy of ivermectin (IVER), doramectin (DORA), and moxidectin (MOXI) subcutaneous (SC) formulations in treated calves. The study was conducted using indigenous (Bos indicus) calves treated with SC formulation at a dosage of 0.5, 0.2 or 0.05 mg/kg body weight (BW) IVER or DORA and 0.2 or 0.05 mg/kg BW MOXI. Direct skin feeding of mosquitoes and animal blood sampling were performed at 4, 8, 12, and 24 h and on days 2, 3, 5, 7, 10, 14, 21, 28, and 35 post treatment. The survival of fully fed A. arabiensis mosquitoes was monitored for 10 days. Plasma samples were analyzed using UHPLC-MS/MS. A. arabiensis mortality percentages in the 0.5 mg/kg BW DORA and IVER groups were 65.74% (95% CI: [54.98; 76.50]) and 64.53% (95% CI: [53.77; 75.29]), respectively, over 35 days post treatment. At the recommended dose (0.2 mg/kg BW), promising overall A. arabiensis mortality rates of 61.79% (95% CI: [51.55; 72.03]) and 61.78% (95% CI: [51.02; 72.54]) were observed for IVER and DORA, respectively. In contrast, A. arabiensis mortality in the MOXI group was 50.23% (95% CI: [39.87, 60.58]). At 0.2 mg/kg BW dose, area under the plasma concentration versus time curve (AUC0-inf) values for IVER, DORA, and MOXI were 382.53 ± 133.25, 395.41 ± 132.12, and 215.85 ± 63.09 ng day/mL, respectively. An extended elimination half-life (T1/2el) was recorded for DORA (4.28 ± 0.93 d), at 0.2 mg/kg BW dose level, compared to that for IVER (3.16 ± 1.47 d). The T1/2el of MOXI was 2.17 ± 0.44 day. A maximum plasma concentration (Cmax) was recorded earlier for MOXI (10 h) than for IVER (1.6 days) and longer for DORA (3.0 days). For DORA and IVER, significant differences were found in T1/2el (P<0.05), Cmax (P<0.01), and AUC0-inf (P<0.01) between the higher 0.5 mg/kg BW and the lower 0.05 mg/kg BW doses. The T1/2el and AUC0-inf of DORA and IVER in the present study were significantly (p < 0.05) correlated with the observed insecticidal efficacy against A. arabiensis mosquitoes at 0.2 mg/kg a dose. Therefore, treating cattle with IVER or DORA could complement the malaria vector control interventions, especially in Ethiopia, where the zoophilic malaria vector A. arabiensis majorly contribute for residual malaria transmission.

Assessment of the magnitude and contributing factors of expired medicines in the public pharmaceutical supply chains of Western Ethiopia.

BACKGROUND: The magnitude of expired medicines in supply chains are increasing globally due to lack of strict control of the supply chain, poor storage management and oversupply of medicines. This situation is very serious in resource-poor countries, including Ethiopia, where the supply of medicines is limited. Therefore, this study aimed to assess the magnitude and the contributing factors of expired medicines in the Public Pharmaceutical Supply Chains of Western Ethiopia. METHODS: Explanatory sequential study design involving mixed quantitative and qualitative approach were employed among 62 public pharmaceutical supply chains of Western Ethiopia from July1 to August 30, 2021. An observational checklist and the self-administered questionnaire were used to review all records of the expired medicine file and to abstract secondary data on the extent, types of expired medicines and its contributing factors. The collected data was cleared, filtered, and coded using Microsoft Excel® 2010, and exported to SPSS version-23 (Amsterdam, Netherland) for statistical analysis. Bivariate logistic regression was used to check association between the outcome and independent variables. Multivariate logistic regression was analyzed when p-value is less than or equal to 0.25 in bivariate binary logistic regression, considering the statistical at p-value < 0.05. Moreover, audio recordings were transcribed and coded for emergent themes using thematic analysis. RESULTS: The study revealed 5% expire rate over past two financial (2012 up to 2013) years and the total amount of expired drugs is estimated at 20 million Ethiopian Birr (ETB). Tetanus antitoxin (TAT), in terms of single drug value, had the highest drug expiry (4,110,426.43ETB: 20%), followed by liquid dosage forms (11,614,266.11 ETB: 57%). The Binary logistic regression result indicated that, poor store management were more likely associated with the magnitude of expired medicine than those with good store management (COR: 10.706, 95% CI: 2.148, 53.348). Multivariate logistic regression revealed that poor store management (AOR: 9.718, 95% CI: 1.474, 64.082) was a significant contributor to the expire rate at 5% (P < 0.05). Most facilities did not have a procedure, and programme for disposing of expired medicines. According to key informants, inadequate inventory management, lack of policy and implementation of standards are the main contributing factors of the medicine's expiration. CONCLUSION AND RECOMMENDATIONS: The current study found that the overall rate of medication expiration is high, at a significant cost to the budget. Inadequate inventory management, lack of policy, and implementation of standards are the main contributing factors to the medicine's expiration, as cited by key informants. Further research is necessary to determine the quality and efficacy of these expired drugs to extend their shelf life to ensure adequate access to drugs in resource-limited settings.

Ethical challenges and dilemmas in the rationing of health commodities and provision of high-risk clinical services during COVID-19 pandemic in Ethiopia: the experiences of frontline health workers.

BACKGROUND: Ethical reasoning and sensitivity are always important in public health, but it is especially important in the sensitive and complex area of public health emergency preparedness. Here, we explored the ethical challenges, and dilemmas encountered by frontline health workers amid the coronavirus disease-19 (COVID-19) pandemic in Ethiopia. METHODS: A nationwide survey was conducted amongst the frontline health workers from nineteen public hospitals. Health workers were invited to respond to a self-administered questionnaire. Data were weighted and analyzed using descriptive statistics. RESULTS: Of the 285 frontline health workers to whom questionnaires were distributed, 217 of them gave their responses (response rate 76.1%). Respondents frequently reported encountering rationing dilemmas on health commodities directly used for the prevention and treatment of COVID-19. Most (83.9%) of the health workers agreed that they encountered ethical challenges very frequently or frequently. Almost all [215(99.1%)] claimed that the limitation of resources was directly used for the treatment and prevention of COVID-19. The frequency of difficulty in the provision of essential clinical services varied between 77% and 98.7% for different services. More than half of the study participants reported that they had encountered difficulty in the provision of clinical care on a daily or weekly basis. Regarding rationing strategies, isolating COVID-19 treatment units and limiting admission were the most frequent rationing strategies used by two-thirds of health workers on a daily or weekly basis. CONCLUSION: Front-line health workers encountered numerous ethically challenging situations during COVID-19. More than half of health workers reported that they encountered ethical challenges in rationing the resources and delivery of different clinical services such as family planning services, maternal and childcare, immunization, and chronic care. With limited resources such as ventilators and hospital beds, healthcare providers have been faced with the difficult task of deciding who gets access to these resources and who doesn't. Overall, the COVID-19 pandemic has presented numerous ethical challenges for healthcare providers, highlighting the importance of ethical considerations in healthcare delivery. By being aware of these dilemmas and having policies in place to address them, healthcare providers can ensure that they are providing the best possible care to their patients while upholding ethical standards.

Effect of seasonal variation on yield and leaf quality of tea clone (Camellia sinensis (L.) O. Kuntze) in South West Ethiopia.

The tea plant is widely cultivated in southwest Ethiopia. But the impact of seasonal variation on monthly yield, leaf quality, and the long-term yield response potential of clones has not been studied. The objective of the study is to determine the impact of seasonal change and climate variables on the yield and leaf quality of tea plants in southwest Ethiopia. The experiment consisted of five clones and four seasons under a split-plot design and was replicated three times. The results indicated that the yield and leaf quality showed significant variation in the different seasons at P < 0.05. The highest peak yields of 12.68, 12.59, and 11.3 kg plot-1 were recorded in May, June, and April, respectively, and the yield suddenly dropped by 5.1% in July. Then the soft banjhi increased by 5-10% in July. The yield response potential of clones is highly affected by monthly climate variation at P < 0.05. Clone BB-35 recorded the highest (18.8 kg plot-1) yield in June, followed by clones 11/4 (18.3) in May, 11/56 (14.7) in November, 6/8 (11.7) in December, and 12/38 (5.78 kg plot-1) in June. The lowest mean green leaf and a longer shoot replacement cycle were created due to a decrease in rainfall to 760 mm/month and rising temperatures above 26.35 °C in winter. The leaf phenological response of tea clones is strongly governed by the monthly temperature and suitable precipitation pattern of a season. The highlands have two harvesting seasons, i.e., a dry and a wet harvesting season. The dry harvesting season, which exists between the middle of December and March, accounts for 18.3-24.3% of the total annual yield. The wet harvesting season is subdivided further into two peak harvesting seasons. The first harvest is characterized by a short plucking round, and the highest peak yield occurs in April, May, and June, accounting for 40.22-42.2% of the total annual yield. The second wet harvesting season begins in September and ends in the middle of December, contributing to 35.5-40% of the annual yield. Seasonal variation has a direct impact on leaf quality and clone yielding potential. Clones show higher yield and shorter plucking rounds at maximum temperatures above 23.03 °C and below 26.35 °C, but temperatures above 28.34 °C and below 10.38 °C have a negative effect on leaf quality and yield. Over the last two decades, rainfall, maximum, and mean temperatures all increased by 16.09 mm y-1, 0.127 °C, and 0.0566 °C y-1, respectively, and the tea plant showed a strong correlation with maximum temperature (76%), whereas mean temperature (44.6%) and annual rainfall (32.8%) correlated weakly. Green leaf production is well explained by around 85.4% of the observed climate variance, with an increase of 1287.18 tonnes y-1, and highland tea production will exhibit a positive net benefit from expected climate change in the future.

Phytochemical Screening and Antimicrobial Activity Evaluation of Selected Medicinal Plants in Ethiopia.

Background: The emergence and spread of resistant microbes continue to be a major public health concern. Effective treatment alternatives, particularly from traditionally used medicinal plants, are needed. Objective: The main objective of this study was to conduct phytochemical screening and antimicrobial activity evaluation of selected traditionally used medicinal plants in Ethiopia. Methods: The ethnomedicinal use value frequency index (FI) was used to select twelve medicinal plants. Phytochemical classes of compounds were screened using different standard methods. Anti-microbial activities of plant extracts were evaluated against Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Candida albicans. Minimum inhibitory concentrations were measured using the broth micro-dilution method. The data were analyzed using Statistical Package for the Social Sciences (SPSS) version 21.0 and the findings were presented descriptively and using non parametric one-way ANOVA analysis (Kruskal-Wallis/Ddunn's test). Results: The phytochemical constituents identified were flavonoids, alkaloids, glycosides, phenols, saponins, steroids, and terpenoids, with flavonoids, alkaloids, and phenols being the most abundant. The crude extracts and chloroform fractions of the extracts showed an activity against the tested strains. The crude extract of Thalictrum rhynchocarpum Quart.-Dill. and A.Rich root demonstrated superior activity against all the tested strains with the lowest minimum inhibitory concentrations of 0.48 µg/mL against Staphylococcus aureus and Escherichia coli; 0.98 µg/mL against Klebsiella pneumoniae, Pseudomonas aeruginosa; and 3.90 µg/mL against Candida albicans, which are even better than the reference drug, gentamicin and clotrimazole. Conclusion: The majority of evaluated medicinal plants demonstrated remarkable activity against tested microbial strains, which can be attributed to the presence of secondary metabolites of different classes of compounds. The finding provided scientific evidence for the use of these traditionally used medicinal plants.

Quality of Antimalarial Drugs in East Africa: A Systematic Review.

Background: The use of poor quality drugs will have multiple consequences with an extended hazard of growing drug-resistant strains. Purpose: The review aimed to provide the quality status of antimalarial drugs in East Africa. Data Source: PubMed, Scopus, Web of Science, and Google Scholar were searched from September 5 to September 12, 2021. Study Selection: The review included articles available as original research targeted at evaluating the quality of antimalarial drugs. For inclusion, data on at least one of the following quality control parameters were required: packaging and labeling, hardness, friability, weight variation/uniformity of weight, disintegration, dissolution, and assay/percentage purity. Mendeley citation manager version 1.19.4 was used to avoid duplication and organize references, and titles and abstracts were primarily used for screening. Data Extraction: The sample collection site, drug name, and the quality control parameters tested were retrieved from the selected studies. Data synthesis:  Totally, 300 antimalarial drug samples from Ethiopia, Kenya and Tanzania were included in this review. No antimalarial drug tested failed the identification and disintegration test. However, 15.93% (36/226), 5.00% (15/300), and 1.90% (3/158) of antimalarial samples failed the dissolution, assay and mass uniformity test, respectively. Moreover, amodiaquine and sulfadoxine/pyrimethamine samples failed dissolution and assay tests. In addition, amodiaquine samples failed the mass uniformity test. However, artemether/lumefantrine and quinine passed all quality control parameters tested. Overall, 19.67% (59/300) of antimalarial drug samples did not meet at least one quality control parameter. And the higher faller rate was reported for sulfadoxine/pyrimethamine accounting for 52.86% (37/70). Conclusions: An unneglected amount of antimalarial drug failed to meet at least one quality control parameter. Strengthening pharmaceutical management systems, including post-marketing surveillance, and providing the resources required for medication quality assurance, are recommended.

Degradation kinetics of artesunate for the development of an ex-tempore intravenous injection.

BACKGROUND: Artesunate is recommended by the World Health Organization (WHO) for parenteral treatment of severe Plasmodium falciparum malaria. However, artesunate is inherently unstable in an aqueous solution and hydrolyses rapidly after its preparation for injection. Therefore, the aim of the study was to evaluate the stabilizing effects of phosphate buffer and mannitol against short-term (ex-tempore) artesunate hydrolysis. METHODS: A HPLC-UV isocratic method was developed using a reversed-phase fused core column (HALO RP-C18) and a mobile phase consisting of a mixture of 45% ammonium formate 10 mM in water (pH 4.5) and 55% methanol. Artesunate was formulated as aqueous solutions using a design of experiment (DOE) to investigate the artesunate stabilizing effects of pH (8-10), phosphate buffer strength (0.3-0.5 M), and mannitol (0-0.22 mmol/mL). The solutions were incubated at predefined temperatures (5, 25, and 40 °C) with subsequent analysis. Arrhenius equation was applied to model and evaluate the stability results. RESULTS: The developed HPLC-based method using fused-core stationary phase allowed to selectively quantify artesunate in the presence of its main hydrolysis degradants; namely ß-dihydroartemisinin (ß-DHA) and α-dihydroartemisinin (α-DHA) within 10 min. By applying the Arrhenius equation, the rate of hydrolysis of the drug increased approximately by 3.4 as the temperature raised by 10 °C. Buffer strength was found to be the main factor affecting the hydrolysis rate constants at 5 and 25 °C (p < 0.05), the activation energy (p = 0.009), and the frequency factor (p = 0.045). However, the effect of the buffer was predominant on the activation energy and hydrolysis rate constants, revealing its stabilizing effect on the drug at lower buffer strength (0.3 M). Within the investigated range (pH = 8-10), pH was found to influence the activation energy, with a positive stabilizing effect in the pH range of 8-9. The addition of mannitol as stabilizing agent into artesunate aqueous formulation did not show an improved response. CONCLUSION: Phosphate buffer was the main stability determining factor of artesunate in the aqueous intravenous (i.v.) formulation and was found to be more effective in stabilizing artesunate at a buffer strength of 0.3 M in pH 8-9, while mannitol lacked stabilizing effect.

Prevalence and intensity of soil-transmitted helminth infections and associated risk factors among household heads living in the peri-urban areas of Jimma town, Oromia, Ethiopia: A community-based cross-sectional study.

BACKGROUND: Ethiopia has set national targets for eliminating soil-transmitted helminths (STH) as public health problems by 2020 and for breaking their transmission by 2025 using periodic mass treatment of children in endemic areas. However, the status of STH infection among the adults living in the same communities remains unknown. The aim of this study, therefore, was to determine the prevalence and intensity of STH infections and associated factors among the household heads in the peri-urban areas of Jimma town, Oromia, Ethiopia. METHODS: A community-based cross-sectional study was conducted in five peri-urban kebeles (smallest administrative unit in Ethiopia) of Jimma town from May to July 2021. A semi-structured questionnaire was used to collect data on socio-demographic and predisposing factors. The Kato-Katz concentration technique was utilized to detect and quantify the STH in stool samples. Both bivariate and multivariate analyses were done. P-value <0.05 was considered statistically significant. RESULTS: A total of 376 household heads (19.9% women and 80.1% men) from peri-urban areas were included in the study. The overall STH prevalence was 18.1% (95% CI: 14.6-22.1) with A. lumbricoides being the predominant species (11.4%) followed by T. trichiura (7.2%) and hookworm (2.1%). Most of the STH positive household heads had single infections (85.3%) and light-intensity infections (88.5%). Wealth status (AOR = 2.7; 95% CI: 1.31-5.50, P = 0.007), hand washing habits before meals (AOR = 7.07; 95% CI: 1.79-27.88, p = 0.005), fingernails status (AOR = 2.99; 95% CI: 1.59-5.65, p = 0.001), and toilet facility type (AOR = 2.06; 95% CI: 1.13-3.76, p = 0.017) were found to have statistically significant associations with the STH infection. CONCLUSION: The findings of this study showed a nearly moderate level of STH prevalence among household heads in the peri-urban community. This could serve as an important reservoir for reinfection of the treated children and other at-risk groups in the community.

Characterization of Boswellia rivae Engl Resin as a Potential Use for Pharmaceutical Excipient.

Pharmaceutical excipients derived from natural sources like resins are nowadays meritoriously used in the formulation of drugs. Resins of natural origin have many advantages over chemically synthesized substances; they are safer, nontoxic, less expensive, biodegradable, and widely available. To our knowledge, resins from plants have been not sufficiently explored for application in pharmaceutical formulations. Thus, in the present study, a resin isolated from Boswellia rivae Engl was characterized for its potential use as a pharmaceutical excipient. Method. The resin was extracted from the oleo gum resin of Boswellia rivae Engl, which involved the removal of volatile oils, gum, and Boswellic acid contents. The dried resin powder was then characterized for its micromeritic properties, heavy metal contents, moisture content, moisture absorption power, pH, solubility, swelling property, and acute toxicity profile. Moreover, the crystal nature and the chemical functionality of the resin were evaluated by using X-ray diffraction and Fourier transform infrared spectrometry, respectively. Results. The yield of the neutral resin was 13.17%, and the powder was pale yellow and had irregular surfaces. The resin was freely soluble in organic solvents but almost insoluble in water. The moisture content of the dried extract was 2.5% while its moisture absorption capacity was 2.5%, 4%, and 5.47% at 40%, 60%, and 75% RH, respectively. Besides, the maximum swelling capacities of the resin observed were 40%, 37%, and 30% at 350C, 300C, and 250C, respectively. The bulk powder exhibited a 1.21 Hausner ratio, 36.497 angles of repose, and 17.03% Carr's index, indicating the fair flowability of the powder. Heavy metals such as zinc, chromium, and cobalt were detected at a low level while elements like copper, manganese, lead, and cadmium were absent. The X-ray diffraction study revealed that the crystallinity index of the powder was 42.7% with a crystal size of 994.5A. The Boswellia resin could be safe in mice up to 3 g/kg of their body weight. In conclusion, the physicochemical properties of the resin powder investigated reveal its potential application as pharmaceutical additives in the formulation of modified release solid dosages forms like tablets and microcapsules.

Antimicrobial Evaluation of Sequentially extracted Leaf of Vernonia auriculifera Hiern (Rejicho).

BACKGROUND: Though there are reports about V. auriculifera antimicrobial activity, there is not enough information about its activity on some bacterial and fungal species. Besides, there was no quantitative evaluation done for phytochemicals previously. Therefore, the main purpose of this research work is to evaluate the antimicrobial activity and quantitative evaluation of the phenol and flavonoid contents of V. auriculifera. OBJECTIVES: The objective of this study was to conduct the antimicrobial and quantitative evaluation of a sequentially extracted leaf of Vernonia auriculifera Hiern. METHODS: The leaves of the plant were cleaned with tap water and air-dried. The grounded leaf product was subsequently extracted by hexane, chloroform, and methanol in maceration flasks. Then the total phenol and total flavonoid content in each extract were determined. Standard strains of bacterial and fungal species were used to assess the antibacterial, and antifungal susceptibility test and to determine the minimum inhibitory concentration of crude extract. RESULT: Extraction yield for hexane, chloroform, and methanol was 0.6 ± 0.05%, 1.7 ± 0.02%, and 3.3 ± 0.01% respectively. The total phenolic content of methanol extract was 72.998 ± 0.002 mg GAE /g. The total flavonoid content of hexane and chloroform extracts were 2.59 ± 0.004 mg QE/g and 9.6 ± 0.02 mg QE/g respectively. The antimicrobial activity test showed the chloroform extract was the most active against all test microorganisms. CONCLUSION: This study has shown the activity of V. auriculifera against selected microorganisms of study. The chloroform extract was the most active as compared to the hexane and methanol extracts.

Influence of clone and nitrogen application level on quality of green tea in some selected tea (Camellia sinensis (L.)O. Kuntze) in Southwest Ethiopia.

The biochemical constituents and organoleptic characteristics of Camellia sinensis (L.) O. Kuntze clones are not studied well in Ethiopia. The study aims to evaluate the polyphenols, caffeine, antioxidant content, and cup quality of clones at different nitrogen application rates and identify suitable clones and processes for daily consumable antioxidant-rich green tea. The experiment consisted of five clones (6/8, BB-35, 11/56, 11/4, and 12/38) and five nitrogen application rates (i.e., 0, 75, 150, 225, and 300 kg ha-1) under a split-plot design and was replicated three times. The biochemical constituents and overall quality of green tea were examined using HPLC, chemical analysis, and a cup taster. The results indicate that the polyphenol content increased slightly (P < 0.018) as the nitrogen application rate increased, with a weak correlation (r = 0.387). The caffeine content varies from 1.82 to 3.06%. Clone BB-35 scored the highest (3.06%), and clone 6/8 scored the lowest caffeine content in all nitrogen treatments. The total nitrogen content varied between 2.27 and 4.01 mg g-1 and slightly increased as the nitrogen application rate increased (r2 = 0.798). The antioxidant activity showed a significant variation (P < 0.001) among clones, and the tested clones had a high antioxidant inhibition percent ranging from 51.9 to 66.5%. The cup quality, aroma, liquor color, and dry leaf appearances of green tea were positively correlated (r = 0.68, r = 0.70, r = 0.48, and r = 0.30), and the overall quality of green tea improved as the nitrogen application rate increased. Clones 6/8 and 11/4 recorded the highest overall quality above the total mean value, whereas clones BB-35, 12/38, and 11/56 scored below the total mean value (77.68%). Clone 6/8 produced an excellent full aroma, balanced bitterness, and a slightly sweeter cup in all nitrogen treatments than other clones. Moreover, this clone contains less caffeine and high polyphenol content in high nitrogen treatment. The second-best, clone 11/4, has a good marketable green liquor, aroma, and dry-made tea appearance, but it is slightly bitterer than clone 6/8. The research concluded that clone 6/8 can produce a more acceptable and high-quality green tea at 300 kg N ha-1.

Knowledge of Malaria and Its Uncomplicated Treatment with Argemone mexicana L. in Selected Districts of Jimma Zone, Oromia Regional State, Ethiopia: A Community-Based Cross Sectional Survey.

Background: With the problems of increasing levels of drug resistance and difficulties to afford and access effective antimalarial drugs in poor and remote areas, herbal medicines could be an important and sustainable source of treatment. Argemone mexicana L. (AM) is a medicinal plant known long ago in several countries for treatment of numerous diseases including malaria. The aim of this study was to conduct a survey on the use of AM in the prevention and treatment of uncomplicated malaria in selected districts of Jimma Zone, Oromia Regional state, Ethiopia. Methods: A community-based cross-sectional study was conducted in two selected districts in Jimma Zone, southwest Ethiopia. In total, 552 participants from 17 kebeles (villages/communities) and 18 traditional healers of the districts were interviewed. Data collection was conducted from April 27 to May 18, 2020 using pre-tested structured questionnaires. The data were analyzed using Epi Info 7.0 and the descriptive statistics were used to summarize the results. Results: The study indicated that AM is available, known by 39.8% of the respondents and used for prevention and treatment of malaria by 5.7% of the population. All traditional healers interviewed knew the plant, and 44.4% use it for treatment of malaria. In addition, AM is especially used to treat malaria, amoebiasis, diarrhea, cough, and tuberculosis. Conclusion: The availability and use of AM to treat malaria was verified in both community and traditional healers. AM, which was found effective as antimalarial plant in high Plasmodium falciparum endemicity in Mali, is also well known and accepted in these areas of Ethiopia for the treatment of malaria. Further research is needed to assess wether AM is also effective against malaria in Ethiopia where P. vivax and P. falciparum coexist.

Evaluation of Policy Governing Herbal Medicines Regulation and Its Implementation in Ethiopia.

Background: Ethiopia is one of the world's oldest countries, with a fascinating history of herbal medicine. However, there is a lack of evidence for the regulatory framework for herbal medicines and its implementation. Thus, the aim of this study was to evaluate the policy governing herbal medicines regulation and its implementation in Ethiopia. Methods and Materials: An archival review, a semi-structured interview with key informants, a cross-sectional study involving traditional healers, and an institution-based cross-sectional survey were conducted from June 15, 2020 to December 25, 2020. The qualitative data was transcribed using Microsoft Word 10, whereas the quantitative data was recorded and analyzed using SPSS 20 computer statistical software. The study's findings are summarized using descriptive statistics. In addition, multiple logistic regressions were performed to identify factors affecting regulation of herbal medicine (HM) in Ethiopia. Variables with p<0.05 were considered potential predictors. Results: According to all key informants, Ethiopia has yet to adopt distinct policies and laws on herbal medicine that may provide an independent regulatory framework. Similarly, the majority of respondents in an institution-based survey indicated that there were no defined policies (n=52, 57.3%), laws (n=53, 59.6%), or registration systems (n=67, 75.3%) for herbal medicine. However, traditional healers claimed that they are licensed by either the Woreda Health Bureau (n=21, 95.5%) or the Regional Health Bureau (n=1, 4.5%) to legally practise traditional herbal medicine. Besides, no traditional healer is licensed by Ethiopian Food and Drug Administration (EFDA) or Ministry of Health. Conclusion: Ethiopia has yet to adopt distinctive herbal medicine policies and laws to provide an independent herbal regulatory system. Despite the fact that the EFDA has a mandate for herbal medicine regulation, traditional healers are licensed by the woreda and regional health bureaus, thus more investigation is needed.

Quality-by-Design Principles Applied to the Establishment of a Pharmaceutical Quality Control Laboratory in a Resource-Limited Setting: The Lab Water.

Quality-by-design (QbD) is defined as a systematic approach to design and develop a product/service based on sound science and quality risk management. It is already frequently applied in the pharmaceutical industry mainly in the development of pharmaceutical products and analytical methods but is not well established in the setup of facilities like quality control (QC) laboratory (lab). Therefore, lab QbD (lQbD) concept is introduced considering lab water purification system as an example. The water purification system comprising distillation unit coupled with Nanopure Analytical Ultrapure Water System combined with a 0.2-micron filter was established in Jimma University Laboratory of Drug Quality (JuLaDQ). The consistent capability of the established water purification system was evaluated through routine monitoring of the critical quality parameters (i.e., physicochemical, HPLC-DAD chromatogram total peak area, and resistivity) of freshly prepared lab water for a period of one year. In addition, quality of different grade water (tap water, distilled water (before and/or after cleaning distillation unit), and fresh ultrapure water (18.2 MΩ × cm at 25°C)) used in JuLaDQ was evaluated. The results of routine analysis of water quality revealed that HPLC global peak area at 210 and 254 nm could serve as one of the discriminatory control strategies to evaluate the capability of water purification system to produce the desired quality of lab water; and thus, we proposed a specification limit of 5,000 mAU∗s and 5,500 mAU∗s for global peak area at 254 and 210 nm, respectively, as system suitability parameter.

Development and Validation of a Reliable UHPLC-MS/MS Method for Simultaneous Quantification of Macrocyclic Lactones in Bovine Plasma.

A fast, accurate and reliable ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for simultaneous quantification of ivermectin (IVER), doramectin (DORA), and moxidectin (MOXI) in bovine plasma. A priority for sample preparation was the eradication of possible infectious diseases to avoid travel restrictions. The sample preparation was based on protein precipitation using 1% formic acid in acetonitrile, followed by Ostro® 96-well plate pass-through sample clean-up. The simple and straightforward procedure, along with the short analysis time, makes the current method unique and suitable for a large set of sample analyses per day for PK studies. Chromatographic separation was performed using an Acquity UPLC HSS-T3 column, with 0.01% acetic acid in water and methanol, on an Acquity H-Class ultra-high performance liquid chromatograph (UHPLC) system. The MS/MS instrument was a Xevo TQ-S® mass spectrometer, operating in the positive electrospray ionization mode and two multiple reaction monitoring (MRM) transitions were monitored per component. The MRM transitions of m/z 897.50 > 753.4 for IVER, m/z 921.70 > 777.40 for DORA and m/z 640.40 > 123.10 for MOXI were used for quantification. The method validation was performed using matrix-matched calibration curves in a concentration range of 1 to 500 ng/mL. Calibration curves fitted a quadratic regression model with 1/x2 weighting (r ≥ 0.998 and GoF ≤ 4.85%). Limits of quantification (LOQ) values of 1 ng/mL were obtained for all the analytes, while the limits of detection (LOD) were 0.02 ng/mL for IVER, 0.03 ng/mL for DORA, and 0.58 ng/mL for MOXI. The results of within-day (RSD < 6.50%) and between-day (RSD < 8.10%) precision and accuracies fell within acceptance ranges. No carry-over and no peak were detected in the UHPLC-MS/MS chromatogram of blank samples showing good specificity of the method. The applicability of the developed method was proved by an analysis of the field PK samples.