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.

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.

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.

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.

Development of a dissolution method for lumefantrine and artemether in immediate release fixed dose artemether/lumefantrine tablets.

BACKGROUND: Dissolution of artemether (ART) and lumefantrine (LUM) active pharmaceutical ingredients (APIs) in fixed dose combination (FDC) ART/LUM tablets is one of the critical quality attributes. Thus, the verification of the release profile of ART and LUM from FDC ART/LUM tablets using a robust and discriminatory dissolution method is crucial. Therefore, the aim of this study was to develop and validate an appropriate dissolution method for quality control of FDC ART/LUM tablets. METHODS: The dissolution medium was selected based on saturation solubility data and sink conditions. The effect of agitation speed, pH and surfactant concentration on the release of ART and LUM was evaluated by employing a two-level factorial experiment. The resulting final method was validated for linearity, precision, robustness and API stability. In addition, the discriminatory power of the method was evaluated using expired and unexpired FDC ART/LUM products. RESULTS: A suitable dissolution profile of FDC ART/LUM tablets was obtained in 900 ml HCl (0.025 N, pH 1.6) with 1%Myrj 52 using paddle method at 100 rpm and 37 °C. ART and LUM were analysed using a HPLC method with UV detection at wavelengths of 210 and 335 nm, respectively. The results from the stability study showed that ART and LUM were sufficiently stable in HCl (0.025 N, pH 1.6) with 1%Myrj 52 at 37 °C. The method was linear (r2 = 0.999) over the concentration range of 6.25-100 µg/ml. The results for precision were within the acceptance limit (%RSD < 2). The percent relative standard deviation (< 2%) and statistically non-significant (p > 0.05) difference in release of ART and LUM observed between deliberately changed dissolution method settings (pH = 1.6 ± 0.2 or agitation speed = 100 ± 2) and optimized dissolution conditions revealed the robustness of the dissolution method. The method was capable to discriminate among different FDC ART/LUM products with different quality. CONCLUSIONS: The developed dissolution method is robust and discriminatory. It can be used in the quality evaluation of FDC ART/LUM tablets.

Quality of fixed dose artemether/lumefantrine products in Jimma Zone, Ethiopia.

BACKGROUND: Malaria caused by Plasmodium vivax and Plasmodium falciparum is among the major public health problems in most endemic areas of the world. Artemisinin-based combination therapy (ACT) has been recommended as a first-line treatment for uncomplicated Plasmodium falciparum malaria almost in all endemic regions. Since ineffectively regulated medicines in resource limited settings could favour infiltration of poor quality anti-malarial medicines into pharmaceutical supply chain and jeopardize a positive treatment outcome, regular monitoring of the quality of anti-malarial medicines is critical. Thus, the aim of this study was to assess the quality of fixed dose combination (FDC) artemether (ART)/lumefantrine (LUM) tablets available in Jimma zone, Ethiopia. METHODS: This study was conducted in Jimma zone, Ethiopia. A total of 74 samples of FDC ART/LUM (20 mg ART/120 mg LUM) tablets were collected from 27 public facilities. All samples were subjected to visual inspection and the relevant information was recorded. The samples were transported to Jimma University Laboratory of Drug Quality (JuLaDQ) and stored at ambient temperature (20 °C to 25 °C) until analysis. The Pharmacopoeial conform/non-conform methods and the risk-based Derringer's desirability function approach were employed to assess the pharmaceutical quality of the investigated products. RESULTS: The visual inspection results revealed that there were no signs of falsified in the investigated products. Identification test results of samples indicated that all samples contained the stated active pharmaceutical ingredients (APIs). The results of uniformity of mass indicated that all samples complied with International Pharmacopoeial specification limits. The assay results, expressed as percent label claim (%lc) of ART (89.8 to 108.8%, mean ± SD = 99.1 ± 3.9%) and LUM (90.0 to 111.9%, mean ± SD = 98.2 ± 3.8%) revealed that, all samples complied with International Pharmacopoeia acceptance specification limits (i.e. 90-110%lc), except one generic product (IPCA Laboratories Ltd., India) which contains excessive LUM (111.9 ± 1.7%lc). The risk priority number (RPN) results revealed that assay (RPN = 392) is relatively the most critical quality attribute followed by identity (RPN = 280) and mass uniformity (40). Quality evaluation based on psycho-physical Harrington's scale revealed that more than 96% of samples were within the acceptable ranges (D ≥ 0.7-1.0). CONCLUSIONS: Both Pharmacopoeial and risk-based desirability function approaches to quality evaluation applied to the investigated products revealed that above 96% FDC ART/LUM tablets circulating in public settings of Jimma zone are of good quality.

Regulatory status of N-alkylamide containing health products.

N-alkylamides (NAAs) are secondary metabolites occurring in more than 25 plant families. Plants containing NAAs are traditionally used in food for flavouring, tingling, pungent and saliva-enhancing properties but also to treat various diseases. NAA containing products are abundantly available on the market as food, cosmetics, medical devices and medicinal products. However, no unambiguous legal product classification is applied for these products. In this study, the different health product classes from a European viewpoint are discussed in relation to the pharmacokinetic and pharmacodynamic properties of the NAAs, their applied dosage and claimed usage.

Determination of the residual efficacy of carbamate and organophosphate insecticides used for indoor residual spraying for malaria control in Ethiopia.

BACKGROUND: Indoor residual spraying is one of the key vector control interventions for malaria control in Ethiopia. As malaria transmission is seasonal in most parts of Ethiopia, a single round of spraying can usually provide effective protection against malaria, provided the insecticide remains effective over the entire malaria transmission season. This experiment was designed to evaluate the residual efficacy of bendiocarb, pirimiphos-methyl, and two doses of propoxur on four different wall surfaces (rough mud, smooth mud, dung, and paint). Filter papers affixed to wall surfaces prior to spraying were analyzed to determine the actual concentration applied. Cone bioassays using a susceptible Anopheles arabiensis strain were done monthly to determine the time for which insecticides were effective in killing mosquitoes. RESULTS: The mean insecticide dosage of bendiocarb applied to walls was 486 mg/m2 (target 400/mg). This treatment lasted 1 month or less on rough mud, smooth mud, and dung, but 4 months on painted surfaces. Pirimiphos-methyl was applied at 1854 mg/m2 (target 1000 mg/m2), and lasted between 4 and 6 months on all wall surfaces. Propoxur with a target dose of 1000 mg/m2 was applied at 320 mg/m2, and lasted 2 months or less on all surfaces, except painted surfaces (4 months). Propoxur with a target dose of 2000 mg/m2, was applied at 638 mg/m2, and lasted 3 months on rough mud, but considerably longer (5-7 months) on the other substrates. CONCLUSIONS: It would appear that the higher dose of propoxur and pirimiphos-methyl correspond best to the Ethiopian transmission season, although interactions between insecticide and the substrate should be taken into account as well. However, the insecticide quantification revealed that the dosages actually applied differed considerably from the target dosages, even though care was taken in the mixing of insecticide formulations and spraying of the walls. It is unclear whether this variability is due to initial concentrations of insecticides, poor application, or other factors. Further work is needed to ensure that target doses are correctly applied, both operationally and in insecticide evaluations.

Intestinal polyparasitism with special emphasis to soil-transmitted helminths among residents around Gilgel Gibe Dam, Southwest Ethiopia: a community based survey.

BACKGROUND: One third of the world population is estimated to be infected with intestinal parasites. The most affected people are children and the poor people living in tropics and subtropics. Polyparasitism (the concurrent infection with multiple intestinal parasite species) is found to be the norm among the same population although accurate estimate of its magnitude is unknown. It was found that polyparasitism might have a greater impact on morbidity than single species infection which might also increase susceptibility to other infections. Therefore, this study aimed at determining the prevalence and distribution of intestinal polyparasitism with special emphasis on Soil-Transmitted Helminths (STH) among residents around Gilgel Gibe dam located in Jimma zone of Oromia regional state, Ethiopia. METHODS: A total of 1,021 participants were recruited in this study and provided stool samples for parasitological examination. Direct wet mount and Kato-Katz techniques were employed for stool examination. Pearson chi-square test was employed to assess the association of infection status and polyparasitism with gender and age group of the study participants. RESULTS: Five hundred thirty two individuals were infected with at least one parasite, providing the overall prevalence of 52.1%. Among positive individuals, 405 (76.1%), 114 (21.4%), and 13 (2.5%) individuals were infected with only one, two and three species of parasites, respectively. The overall prevalence of intestinal polyparasitism observed among the study participants was 12.4% (127/1,021). The predominant STH was hookworm, with a prevalence of 44.1%. Hookworm and Ascaris lumbricoides were the most frequently recorded combination in cases of polyparasitic infection. The study revealed that there was no significant difference in the distribution of polyparasitism with regard to age group and sex of the study participants (p > 0.05). CONCLUSION: The study indicated the presence of high prevalence of parasites as well as distribution of polyparasitism in the area. Moreover, the detection of Schistosoma mansoni in the community living within close proximity of the newly constructed dam would be taken as an indication of future risk factor. Further investigation on the predictors of polyparasitism and the assessment of effects of polyparasitism on the population are needed. Finally, there is a need to undertake integrated control strategies which involve improved sanitation, health education and chemotherapy that targets the whole community instead of only certain segments of populations.

Assessment of therapeutic efficacy and safety of artemether-lumefantrine (Coartem®) in the treatment of uncomplicated Plasmodium falciparum malaria patients in Bahir Dar district, Northwest Ethiopia: an observational cohort study.

BACKGROUND: Malaria is a complex disease, which varies in its epidemiology and clinical manifestation. Although artemether-lumefantrine has been used as first-line drug for uncomplicated Plasmodium falciparum malaria in Bahir Dar district since 2004, its efficacy has not yet been assessed. The main objective of this study was to quantify the proportion of patients with uncomplicated falciparum malaria who were prescribed artemether-lumefantrine and who failed treatment after a 28-day follow-up. METHODS: The research team attempted to conduct an observational cohort study on the assessment of therapeutic efficacy and safety of artemether-lumefantrine in falciparum malaria patients aged over five years in Bahir Dar district from March to July 2012. RESULTS: Among 130 participants in the study, 60% were males with 1:5 male to female ratio. The mean of asexual parasitaemia load was 8675 parasites/µL and 96.1% participants were free from parasitaemia at day 3. At the end of the study, 98.5% of participants showed adequate clinical and parasitological response of the drug. In the study, only 1.5% of participants were shown late parasitological failure between seventh and 14th day follow-up and 1.3% of participants were free from anaemia at the end of follow-up. CONCLUSION: According to the research findings, artemether-lumefantrine fulfilled the inclusion criteria of WHO as first-line drug and continues to be the drug of choice for the treatment of uncomplicated falciparum malaria. Outputs from this study should be supported through advanced molecular techniques and blood concentration and pharmaco-vigilance of the drug.

A community-based cross-sectional study of the epidemiology of onchocerciasis in unmapped villages for community directed treatment with ivermectin in Jimma Zone, southwestern Ethiopia.

BACKGROUND: Human onchocerciasis is a neglected tropical parasitic disease caused by Onchocerca volvulus (O. volvulus) that may result in devastating skin and eye morbidity. Even though the disease is targeted for elimination, there was little or no information on the level of onchocerciasis endemicity for implementation of community directed treatment with ivermectin (CDTI) in the current study area. Thus, this study aimed at investigating the epidemiology of onchocerciasis and the level of awareness towards the disease among communities living close to CDTI area, Jimma Zone, southwestern Ethiopia. METHODS: A community based cross-sectional study was conducted from April 23 to May 22, 2012. Data on socio-demographic characteristics, knowledge, attitude and practice towards onchocerciasis were collected using semi-structured questionnaires. Clinical examination was undertaken for onchocercal skin diseases by experienced health professionals. Moreover, two skin snip samples were collected from the right and left gluteal folds. Study participants found positive for O. volvulus infection during the study were treated individually with standard dose of ivermectin as per WHO guideline. RESULTS: The overall prevalence of O. volvulus infection was 22.5 % while the prevalence of onchocercal skin diseases was 29.8 %. The community microfilarial (mf) load was 5.70 mf per skin snip. Age, sex, educational status, occupation and duration of stay in the villages showed significant association with onchocerciasis (P < 0.05). But sex (OR = 0.565, 95 % CI = 0.335, 0.952), educational status (OR = 0.545, 95 % CI = 0.310, 0.958) and duration of stay in the village (OR = 5.933, 95 % CI = 1.017, 34.626) were the independent predictors for O. volvulus infection. Three hundred eighty eight (88.2 %) of the study participants reported that they didn't know about onchocerciasis. CONCLUSIONS: There was moderate prevalence of onchocercal infection and onchocercial skin diseases (OSD) in the study area. Result of this study may suggest that the endemicity level of onchocerciasis in the study area was mesoendemic. Hence, intervention using ivermectin treatment should be implemented to reduce the burden of onchocerciasis. Since the majorities of the population had poor knowledge, attitude and practice towards onchocerciasis, inclusion of health education in the intervention package is crucial.

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.

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.

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.

A rapid stability-indicating, fused-core HPLC method for simultaneous determination of ß-artemether and lumefantrine in anti-malarial fixed dose combination products.

BACKGROUND: Artemisinin-based fixed dose combination (FDC) products are recommended by World Health Organization (WHO) as a first-line treatment. However, the current artemisinin FDC products, such as ß-artemether and lumefantrine, are inherently unstable and require controlled distribution and storage conditions, which are not always available in resource-limited settings. Moreover, quality control is hampered by lack of suitable analytical methods. Thus, there is a need for a rapid and simple, but stability-indicating method for the simultaneous assay of ß-artemether and lumefantrine FDC products. METHODS: Three reversed-phase fused-core HPLC columns (Halo RP-Amide, Halo C18 and Halo Phenyl-hexyl), all thermostated at 30°C, were evaluated. ß-Artemether and lumefantrine (unstressed and stressed), and reference-related impurities were injected and chromatographic parameters were assessed. Optimal chromatographic parameters were obtained using Halo RP-Amide column and an isocratic mobile phase composed of acetonitrile and 1 mM phosphate buffer pH 3.0 (52:48; V/V) at a flow of 1.0 ml/min and 3 µl injection volume. Quantification was performed at 210 nm and 335 nm for ß-artemether and for lumefantrine, respectively. In-silico toxicological evaluation of the related impurities was made using Derek Nexus v2.0®. RESULTS: Both ß-artemether and lumefantrine were separated from each other as well as from the specified and unspecified related impurities including degradants. A complete chromatographic run only took four minutes. Evaluation of the method, including a Plackett-Burman robustness verification within analytical QbD-principles, and real-life samples showed the method is suitable for quantitative assay purposes of both active pharmaceutical ingredients, with a mean recovery relative standard deviation (± RSD) of 99.7 % (± 0.7%) for ß-artemether and 99.7 % (± 0.6%) for lumefantrine. All identified ß-artemether-related impurities were predicted in Derek Nexus v2.0® to have toxicity risks similar to ß-artemether active pharmaceutical ingredient (API) itself. CONCLUSIONS: A rapid, robust, precise and accurate stability-indicating, quantitative fused-core isocratic HPLC method was developed for simultaneous assay of ß-artemether and lumefantrine. This method can be applied in the routine regulatory quality control of FDC products. The in-silico toxicological investigation using Derek Nexus® indicated that the overall toxicity risk for ß-artemether-related impurities is comparable to that of ß-artemether API.

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.

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.