School of Pharmacy

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    A Queuing Analysis of Medicines Registration System Performance in Ethiopian Food and Drug Authority
    (Addis Ababa University, 2023) Alamneh,Abebe; Ali,Eskinder Eshetu(Dr.); Marew,Tesfa
    Background: The limited number of approved medicines and long waiting time for registration are the major challenges limiting the performance of the regulatory system in Ethiopia. Queue analysis is used for characterizing and estimating the queue process and operating variables of the system to alleviate the challenges related to target timelines. Objective: To assess the queuing performance of the registration system at the Ethiopian Food and Drug Authority (EFDA). Methods: A mixed sequential explanatory study design was used for the study. Quantitative data collection involved a review of applications submitted to the EFDA from July 8, 2019 to July 7, 2020. Basic operating characteristics of the registration system performance were executed using single queue multiple server model of the queuing analysis. In-depth interviews with purposively selected registration experts from the EFDA and private organizations were done for the qualitative data collection. Analysis of the interviews involved the thematic analysis approach. Results: Mean arrival rate of applications to the registration system (λ=10.99 services per day) was 23.74% higher than the mean effective service rate of the system (cμ=8.38 services/day). Basic system performance average operating characteristics of the system could not be estimated indicating that an infinite queue of applications built up over time and was hard to achieve any target timeline in EFDA’s current registration system. The qualitative study also showed that the system is being frequently challenged with backlogs. Conclusion: The study documented weak system performance with lengthy registration process. Appropriate measures to improve mean effective registration service rate should be introduced to meet international standards and the agreed citizen’s charter of 2016.
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    Acceptability of Azithromycin Mass Treatment for Trachoma Elimination in Injibara Town and Adjacent Banja Woreda of Awi Zone, Amhara Region
    (Addis Ababa University, 2014-06) Tilahun, Zelalem; Gedif, Teferi(PhD)
    Trachoma is the leading cause of infectious blindness worldwide. Globally 1.2 billion people live in endemic areas. In Ethiopia, approximately 67 million people are at risk for trachoma. The Amhara National Regional State of Ethiopia is the most trachoma-endemic among all nine regional states and two city administrations, with Trachomatous inflammation Follicular prevalence of 62.6%. Mass azithromycin treatment is the one arm of the SAFE strategy. The trachoma elimination program would be successful if and only if the coverage is as high as possible with full community participation. If not all the community members attend the mass treatment, the trachoma infection will return to the baseline prevalence after the treatment stopped due to high transmission rate. The objective of this study was to assess the acceptability of the azithromycin mass treatment and its determinants in Injibara town and the adjacent Banja woreda of Awi zone, Amhara National Regional State. A community based cross sectional survey with both quantitative and qualitative methods was conducted from July 7-25, 2013. Households’ survey with structured questionnaire, FGDs and key informant interviews were used for data collection. A total of 5826 eligible household members from 1267 households were enrolled in the survey. The 2012 annual azithromycin mass treatment coverage obtained from the present study was 92.9%. From the total 6 rounds of azithromycin mass treatment in the study area, only half (50.6%) of the community took for more than three times. On average, each illegible person in the community had taken the drug for 3.6 times. The percentage of rural household members who had taken azithromycin more than three times was higher than the corresponding urban members. The rural residents were at better performance in taking the 2012 treatment as compared to the urban residents (AOR=2.35; 95%CI [1.80-3.06]). Household heads interference with the drug uptake of their family members’ has negative association with azithromycin uptake (AOR=0.153; CI=95% (0.086-0.272). All the study participants who were X greater than 30 years more likely took azithromycin more than 3 times as compared with children less than 15 years (COR=2.81, AOR=2.74, 95% CI [1.95-3.02]). Azithromycin uptake status of female household heads was less than the corresponding male household heads (AOR=0.41; 95% CI [0.24-0.720]). Household heads awareness about trachoma (AOR=2.55; 95% CI [1.19-5.44]) and azithromycin mass treatment (AOR=7.19; 95% CI [3.27-15.82]) had positive association with acceptability. The 2012 azithromycin mass treatment coverage in Injibara town and Banja woreda was higher than the WHO minimum target. But, concerning to the overall coverage, the data taken from the present study contradicts the coverage data taken from the woreda. The communities’ Azithromycin mass treatment acceptability had increased in the recent campaigns as compared to the previous campaigns. There is low coverage and acceptability of the treatment in the urban community as compared to the rural residents. Supplementary benefits of azithromycin, health education about trachoma and the drug, willingness and being old are some of the factors positively related with acceptability whereas educational status, marital status and experience with side effects were not associated with the drug uptake status. Strengthen the program in the urban and consideration of additional campaigns for both areas as well as providing additional health education with skilled health professionals is mandatory. Key words: Azithromycin mass treatment, Mass drug administration, Acceptability, Trachoma, Trachoma elimination
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    Access to Essential Psychotropic Medicines in Addis Ababa: A CrossSectional Study
    (Addis Ababa University, 2022-01) Ayehu, Molla Teshager; Prof.Fenta, Teferi Gedif; Prof.Araya, Mesfin
    Background: Mental disorders are becoming a growing public health problem worldwide, especially in low- and middle-income countries. To provide quality mental health services, regular and adequate supplies of appropriate, safe and affordable medications are required. However, significant percentages of people with severe mental disorders are not getting the treatment. Availability and affordability of psychotropic medicines, amongst others, are the major barriers for many patients in meeting their medication needs. This study aimed to assess the availability, prices and affordability of essential psychotropic medicines in the private and public health sectors of Addis Ababa city. Methods: A cross-sectional study design was used in 60 retail medicine outlets. Quota sampling and purposive sampling was applied to select the retail outlets. Data was entered and analyzed by using the pre-programmed WHO/HAI workbook and SPSS version 25. Outcome measures were described as percentage availability, median price and median price ratios, and the number of days' wages needed to purchase medicines by the lowest-paid unskilled government worker. Finally, the results were presented as statements, tables, figures and graphs. Results: The mean availability of LPG psychotropic medicines was 24.33% in Addis Ababa (28.7% in the public sector and 19.80% in the private sector), and of OB medicines were 2.42 %( 2% in the private and 2.8% in the public sectors). Similarly, the public procurement prices for 16 LPGs ranged from 0.25-4.83 MPRs and the median procurement price was 0.96 MPR. The patient prices for the LPGs ranged from 0.52-6.43 MPRs in public and 1.08- 24.28 MPRs in private sectors. The patient prices for OB medicine were 5.21 MPR in public and 11.17 in private sectors. The cost of standard treatment varied from 0.1–7.8 days' wages in public and 0.8-25 days' in private sectors for the lowest-paid government worker to purchase a month's supply. Conclusions: Essential psychotropic medicines were poorly available with high prices and low affordability in Addis Ababa. To ensure access, an efficient supply across all levels of care and financial protection for key medicines should be in place.
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    Activity Testing, Toxicity Assay and Characterization of Chemical Constituents of Medicinal Plants Used to Treat Tuberculosis in Ethiopian Traditional Medicine
    (Addis Ababa University, 2016-04) Kahaliw, Wubayehu; Engidawork, Ephrem (PhD); Abebe, Markos (PhD)
    Background: Tuberculosis (TB) is the leading killer disease worldwide. In 1993, WHO declared TB as a ‘global emergency,’ which requires emergency action and launched several programs to curb the disease, including the search for newer remedies and/or anti- TB agents to complement currently used agents. Hence, herbal remedies have become the readily available alternatives in the search for new antimycobacterial compounds. Objective: To investigate antimycobacterial activity and toxicity of selected Ethiopian medicinal plants (Otostegia integrifolia, Vernonia amygdalina, Persea americana, Pterolobium stellatum and Carissa edulis) as well as to isolate the main active principles through a bioassay guided process. Methods: Antimycobacterial activity test was conducted using the broth microdilution and microtitre resazurin assay methods in 96 well microtitre plates and MIC was determined by colony counting and resazurin color change observation for all test materials. Cytotoxicity test was performed based on the CellTiter 96® AQueous One Solution Cell Proliferation Assay on HepG2 cells. Genotoxic effects of extracts were evaluated using SCGE method on HepG2 cells. Results: Chloroform and 80% methanol extracts of P. stellatum and O. integrifolia as well as 80% methanol and acetone extracts of P. americana had significant antimycobacterial activity (p < 0.001) against M. tuberculosis H37Rv, while chloroform extract of V. amygdalina and C. edulis didn’t show significant activity compared to negative controls. The MIC of positive control was 0.125 μg/ml against the standard strain. However, MDR-TB clinical isolates were isoniazid resistant. Fractionation and activity testing of the chloroform extract of P. stellatum revealed that ethyl acetate ii fraction to be the most active fraction against M. tuberculosis H37Rv with MIC of 0.195 μg/ml. The MICs of compound 1, 2 and 3 were 1.25, 2.5 and 0.625 μg/ml, respectively. In the cytotoxicity test, V. amygdalina chloroform extract showed the highest IC50 value (3.202±0.3375), which suggests its safety. O. integrifolia and P. stellatum chloroform extracts were the most toxic in dose dependent manner as one can see the steepness of the dose-response curve. DNA damage in the form of comet tail has been observed for 1 and 0.5 mg/ml P. stellatum chloroform and 80% methanol extracts on HepG2 cells, respectively. The rest of test extracts seemed to be without genotoxic effect up to a concentration of 0.5 mg/ml. Cytotoxicity test was not in the objectives of my study. Conclusion: P. stellatum, O. integrifolia and P. americana have potential to be developed into new anti-TB drugs or standardized herbal medicines. P. stellatum chloroform extract was the most active extract and hence, three compounds were isolated from ethyl acetate fraction and they were active against M. tuberculosis H37Rv. The results have also validated indigenous medical knowledge from the local people regarding the use of these species to treat TB. The IC50 value of P. stellatum chloroform extract was relatively higher compared to other extracts, suggesting its safety. In addition, its selectivity index was 13.5, which demonstrated > 10 selectivity index, considered as being of interest to the pharmaceutical companies. The genotoxicity assay findings revealed that the chloroform and 80% methanol extracts of P. stellatum caused DNA damage at 1 mg/ml and 0.5 mg/ml concentrations. Thus, necessary precautions should be taken during utilization of this plant.
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    Analgesic and Antinflammatory Activities of the Root extract of Grewia schweinfurthii and its Constituent and Determination of Nutritional and Antinutritional Compositions of its Fruit
    (Addis Ababa University, 2023) Leta,Abdi; Hymete, Ariaya (PhD); Tadesse,Solomon(PhD); Giday,Mirutse(PhD)
    The utilization of current treatments can often result in harmful side effects, and cause patients to experience pain and inflammation. In Ethiopian, traditional healers have relied on medicinal herbs, such as Grewia schweinfurthii, which possess analgesic and anti-inflammatory properties. Despite their widespread use, studies regarding the nutritional content of wild edible plants (WEPs) in low-income nations like Ethiopia are limited. This study aimed to evaluate the analgesic and anti-inflammatory effects of 80% methanolic root extract of G. schweinfurthii and its chemical constituents, as well as to examining the nutritional and antinutritional content of its fruit. The root extract of G. schweinfurthii and its constituents were evaluated for their analgesic activity using acetic acid-induced writhing and hot plate tests. The root extract was subjected to column chromatography (silica gel) to isolate a compound coded as AL-03 and tentatively identified as 4-(2''-(4'-isopropylphenyl) propan-2''-yl)-2,3-dihydrofuran based on spectroscopic (1H, 13C NMR & HSQC) data. The root extract G. schweinfurthii demonstrated significant analgesic activity (p < 0.001) in the acetic acid-induced writhing test at doses of 200 and 400 mg/kg. Additionally, in the hot plate method, a dose of 400 mg/kg of root extract showed noteworthy analgesic activity (p < 0.001). In the carrageenan-induced acute inflammation model, all doses (100, 200, 400 mg/kg) of the root extract resulted in a significant decrease in paw edema compared to the negative control. Compound AL-03 also exhibited antinflammatory activities in a dose-dependent manner against carrageenan-induced paw edema. XI Proximate analysis was used to assess various nutritional parameters of G. schweinfurthii fruit, including crude protein, fat, total ash, crude fiber, and carbohydrates. In this regard, G. schweinfurthii fruit revealed the following composition: moisture (4.09 ± 0.10%); crude protein (11.24 ± 0.68%); fat (1.99 ± 0.01%); total ash (5.36 ± 0.20%); crude fiber (32.50 ± 0.50%); carbohydrate (44.82 ± 0.82%); and total energy (242.12 ± 1.72 kcal). Furthermore, phytate (62.97 ± 0.83%), tannin (3.97 ± 0.12%), and oxalate (0.28 ± 0.03%) were identified as antinutritional components. Overall, G. schweinfurthii fruit was found to be a reliable source of nutrients and bioactive compounds. The findings support the traditional medicinal use of the plant for analgesic and antinflammatory activities. Further research is recommended to explore additional bioactive compounds from the root extract of G. schweinfurthii and to analyze the mineral composition, such as amino acids, and vitamin C content of G. schweinfurthii fruit, as well as to conduct sub-acute and chronic toxicology testing
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    Anthelmintic Activity of the Seed Oil of Ricinus communis
    (Addis Ababa University, 2023-03) Berhanu,Temesgen; Asres, Kaleab(Prof.); Bisrat, Daniel(Dr.)
    Helminthic infections are among the most widespread parasitic infections in humans. It is estimated that more than half of the world’s population suffer from parasitic infections. It poses morbidity particularly in children and pregnant women. Helminthic infections are more common in developing countries with poorer personal and environmental hygiene. Plant-derived drugs and herbal remedies remain important resources to alleviate and cure diseases, especially in developing countries. Variety of plants from various families including Ricinus communis from the family Euphorbiaceae are used to treat helminthiasis across the world. R.communis is an annual oilseed crop commonly known as castor. Antimicrobial, antifungal, anticancer, antidiabetic, anti-inflammatory and antimalarial are some of the pharmacological activities that have been reported from extracts of R. communis. In the present study, the petroleum ether seed extract of R. communis, its base hydrolysate and the major constituent of the hydrolysate were tested for their anthelmintic activities against the model organism Caenorhabditis elegans. The dried and powdered seeds were extracted using petroleum ether and then the oil collected was subjected to base hydrolysis to obtain the hydrolysate. Fractionation of the hydrolysate by column chromatography packed with silica gel 60-G resulted in the isolation of the hydroxylated fatty acid (9Z)-12-hydroxyoctadec-9-enoic acid (ricinoleic acid). The isolated free fatty was esterified by 5% Potassium hydroxide solution in methanol to get ricinoleic acid methyl ester. Structural elucidation of the compounds was achieved by spectroscopic techniques including ESI-MS, 1H and 13C-NMR spectral data. Results of the anthelmintic assay revealed that VIII ricinoleic acid and its methyl ester are strongly active against C. elegans worms compared to the oil. Ricinoleic acid exhibited 97% mortality at the tested concentration of (1 mg/ml). In conclusion, the present study demonstrated that the oil of R. communis seeds possesses strong anthelmintic activity against the model nematode C. elegans worms and the activity of the oil would be attributed to the presence of ricinoleic acid as a major constituent.
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    Anti Tuberculosis Drug Induced Hepatotoxicity in Hiv Positive and Negative Patients
    (Addis Ababa University, 2005-06) Yimer, Getnet; Aseffa, Abraham(PhD)
    Anti-tuberculosis drug induced hepatotoxicity (DIH) is a common problem in the management of tuberculosis. This study was intended to identify possible risk factors for development of DIH, including degree of immunosuppression. In this prospective 2-month cohort study, 103 HIV positive and 94 HIV negative newly diagnosed tuberculosis patients were followed after initiation of DOTS (direct observed treatment short course). CD4 count was measured for the HIV positive patients. All patients were also evaluated for different risk factors including HBsAg, Anti-HCV, alcohol intake, use of other drugs including traditional medicines, acetylation status and presence of chronic illness. Patients were monitored biochemically (by liver function tests) and clinically for development of DIH weekly in the first month and bi-weekly in the second month after start of therapy. Biochemical hepatotoxicity was seen in 17.3% of the patients. CD4 counts of these patients were 0-50 for 7 (35%), 51-100 for 8 (40%), 101-200 for 4 (20%), and > 200 for 1 (5%). Three patients were positive for HBsAg and none had anti-HCV. Five patients died of non-hepatic causes among the patients who developed DIH. Eight out of the 34 patients with biochemical hepatotoxicity (23.5%) developed clinical hepatotoxicity that necessitated discontinuation of their anti-TB drugs. Seven of the eight were HIV positive, seven were female, and 2 were positive for HBsAg. Biochemical hepatotoxicity was significantly associated with HIV co-infection (p=0.002), concomitant drug intake (p=0.008), decrease in CD4 count (p=0.001), high mortality (p=0.001), and having Wt/Wt allele for acetylation status (p=0.026). Clinical hepatotoxicity is also significantly associated with being female (p=0.027), HIV co-infection (p=0.043), concomitant drug intake (p=0.003), HBsAg (p=0.046), decrease in CD4 count (p=0.025), and high mortality (p=0.0001). No significant association was seen between hepatotoxicity with alcohol intake, age, body mass index, type of TB and anti HCV positivity. The findings would assist in selectively managing patients at risk. It is recommended to have a regular biochemical and clinical follow up for those patients who are at risk of developing DIH .These patients include HIV positive patients, with special emphasis to those with a lower CD4 count, and patients who take drugs other than their anti TB medication. We also recommend that further work should be done to explore the reason for the observed association between DIH and female sex, HBsAg positivity, and acetylation status. Key words: Tuberculosis, HIV, Hepatotoxicity, Acetylation status, NAT2 gene
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    Anti-Malarial Drug and Mosquito Net Use Pattern in Pawe Special Woreda: A Community Based Survey
    (Addis Ababa University, 2009-06) Mussa, Seid; Gedif, Teferi (PhD)
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    Anti-Malarial Drug and Mosquito Net Use Pattern in Pawe Special Woreda: A Community Based Survey
    (Addis Ababa University, 2009-07) Mussa, Seid; Gedif, Teferi (PhD)
    Background: Malaria is a major public health problem and the leading communicable disease in Ethiopia. Interruption of contact between humans and mosquitoes through the use of insecticidetreated bed nets (ITNs) is a promising approach to protect people from malaria infection. Treatment failures and mortality due to malaria has risen in recent years, probably due to increasing resistance to anti-malarial medicines. Improper drug storage and rampant selfmedication are some of the factors that may contribute to an increase in the development of drug resistance by malaria parasites towards anti-malarials. Study objective: To assess the utilization pattern of anti-malarial drugs, and mosquito net coverage in Pawe special Woreda, Beneshangul-Gumuz National Regional State. Methodology: The study was conducted in Pawe Special Woreda, Beneshangul-Gumuz Regional State between August and September 2008. Both quantitative and qualitative methods were employed in the data collection. Qualitative methods employed include focus group discussions and key-informant interviews. The quantitative method used is a community based cross-sectional household survey. The study utilized a trained interviewer administered questionnaire for data collection. Data was collected primarily from mothers. Quantitative data was entered using EPI-Info software Version 6.04 and analyzed by SPSS version 11 statistical packages. Qualitative data were analysed through thematic content analysis in an attempt to answer key questions of the study. Results: Perceived malaria prevalence was found to be 6.1 %. Sixty nine, (38.8%) of those with reported malaria/symptom complexes in the last two weeks preceding the interview date se lfmedicated themselves with anti-malarials. Households with a family size of less than or equal to 5 persons (OR=0.47, CI=0.25, 0.90, P=0.02) were less likely to self-care with anti-malarials than those with a family size of more than 5 persons.
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    Anti-TB Medicines Supply Chain Management Practices and Related Challenges in Gurage Zone Public Health Facilities, Southern Ethiopia
    (Addis Abeba University, 2021-09) Gezahagn, Sifrash; Dr. Ali, Eskinder Eshetu
    Introduction: Gaps in managing the supply chain of anti-tuberculosis (TB) medicines result in supply interruptions posing significant health-related and economic consequences. Objective: To assess anti-TB medicines supply chain management practices and related challenges in Gurage Zone public health facilities. Methods: A concurrent/parallel explanatory mixed methods design was followed in this study. Institutional based cross-sectional study was conducted from August to September, 2020. Simple random and purposive sampling was used to select study participants. A structured questionnaire and observational check list was used to collect quantitative data and analyzed using Microsoft Excel 2013 and SPSS version 25. For the qualitative part, an interview guide was used to collect data from fifteen key informants and analyzed thematically. Results: Twenty public health facilities (HFs) in Gurage Zone providing TB management and care were included in the study. Majority of the HFs (18, 90%) were using only stock recording cards to control the inventory of anti-TB medicines. The average physical stock count corresponding to inventory recorded count for a set of anti-TB medicines was 76.6%. For a set of anti-TB medicines the average availability was 82.6% and the average stock out duration was 11.23 ± 1.38 days per a year (Min=0, Max=115). The average wastage rate for a set of first-line anti-TB medicines was 4.78%. Qualitative interviews showed the absence of computerized drug management system to manage anti-TB drugs supply chain and the lack of healt h facilit ies’ involvement in drug quantification as major barriers for the effective management of anti-TB medicines supply. Conclusions: The most current version of the national TB treatment guidelines and job aids were not available in the majorit y of public healt h facilities and it was also noted that quantificat ion of ant i-TB drugs was a major problem. In majorit y of the health facilit ies storage condit ion needs early intervent ions and inventory control system was totally manual.
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    Anti-ulcer activity of aqueous root extract of Ensete ventricosum (Welw.) Cheesman (Musaceae) in experimental rats
    (Addis Abeba University, 2021-07) Hailu, Dejene; Shibeshi, Workineh (PhD); Umer, Shemsu (PhD); Arayaselassie, Mahlet (MD)
    Peptic ulcer is a chronic disease of gastrointestinal system caused by an imbalance between damaging factors and protective factors. Even though many antiulcer drugs used to treat this disease are available, most of these drugs produced undesirable side effects, microbial resistance and danger of drug interactions during therapy. An ethnobotanical study showed that Ensete ventricosum is used for treatment of peptic ulcer but the efficacy and safety are not established. Thus, this study was aimed to evaluate the anti-ulcer activity of aqueous root extract of Ensete ventricosum (E. ventricosum) in experimental rats. The effect of the extract on gastric ulcer was evaluated against indomethacin, ethanol and pyloric ligation-induced ulcer models at doses of 100, 200 and 400mg/kg. Dose levels were selected based on outcome of acute toxicity study. Pantoprazole at a dose of 40mg/kg was used as a standard drug while distilled water was used as negative control. In indomethacin and ethanol-induced ulcer, pretreatment with aqueous root extract of E. ventricosum significantly reduced level of gastric mucosal ulceration and improved ulcer protection. Furthermore, histopathological findings of rats pretreated with aqueous root extract of E. ventricosum also revealed gastroprotective activity. In pyloric ligation-induced ulcer, administration of E. ventricosum at a dose of 200 and 400mg/kg significantly (p<0.05) reduced both ulcers number and severity scores and histopathological findings also revealed gastroprotective activity of the extract. The extract at a dose of 400mg/kg exerted best ulcer protection (98.53%) which was comparable to standard drug in pyloric ligation-induced ulcer as compared to other models studied. The extract at a dose of 200 and 400mg/kg also displayed antisecretory activity as revealed by significant (p<0.05, p<0.001) reduction in volume, free and total acidity of gastric juice with significant (p<0.05, p<0.001) increment in pH of the gastric juice in both ethanol and pyloric ligation-induced ulcer in dose dependent manner. In conclusion, the aqueous root extract of E. ventricosum showed significant antiulcer activity.
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    Antibiotic Use Practice and Predictors of Hospital Outcome Among Patients with Systemic Bacterial Infection at Tikur Anbessa Specialized Hospital: Identifying Targets for Antibiotic and Health Care Resource Stewardship
    (Addis Ababa University, 2015-04) Alemkere, Getachew; Tenna, Admasu(PhD)
    Background: Despite massively used in different settings, about half of antimicrobial agents prescribed to hospital in-patients were considered inappropriate. Such malpractice and excess use has been associated with increased mortality, adverse drug reactions, financial cost and the development of resistant bacteria, which have become a threat for the generation. These calls for an integrated intervention that should better are preceded with identification of targets. Objective: To assess the antibiotic use practice and to identify predictors of hospital outcome among patients with systemic bacterial infection to uncover targets for antibiotic and health care resource stewardship Methods: A prospective cross-sectional study was performed from 9 April to 7 July in the internal medicine wards of Tikur Anbessa specialized Hospital. Patients who had and/or developed systemic bacterial infections during this period were strictly followed. Data abstraction format was used to collect data on demographic, disease, drug and microbiologic related factors. Pattern of antibiotic use was assessed and predictors for mortality and length of stay (LoS) were identified. Descriptive statistics and Binary logistic regression were used for statistical analysis. Results: Females accounted for about 52% of the 323 study participants whose mean age was 41.8. Of all, 75.2% of the participants had suspected infection during ward admission. Cephalosporins were the most widely prescribed class of drugs in the internal medicine wards and the medical ICU. Based on changes to microbiologic culture reports the initial antibiotic uses were inappropriate in all of the ICU and 99.3% of the ward patients. About 28% of the wards and 59% of the ICU patients were died during the in-hospital stay. The mean (+ SD) LoS was 18.5+12.2 in the wards and 8.9+4.9 days in the ICU. Whilst presence of HIV, liver-cirrhosis, different signs and symptoms of disease, neoplasm, sepsis, meningitis, renal failure, vancomycin and increased antibiotic courses (> 2) were iv positive predictors, prolonged antibiotic days (>10) and simultaneous antibiotic uses (>3) were negative predictors of mortality. On the other hand, age range of 25-44, hospital acquired infection and prolonged agent days (>21) (positively) and on admission infection (negatively) were independently associated with prolonged LoS. Conclusion: Generally, these observations call for the establishment and implementation of antimicrobial stewardship that facilitate appropriate use of antimicrobials as a whole in the context of resource limited settings. Any stewardship activity should better start by addressing infections like pulmonary, sepsis and meningitis and drugs like vancomycin. Key words: Antimicrobial Stewardship, Antibiotic use, Length of Stay, In-hospital Mortality, Tikure Anbesa Specialized Hospital, Ethiopia
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    Antibiotics self-medication practices among health care professionals in selected public hospitals of Addis Ababa
    (Addis Ababa University, 2019-03) Kassa, Tsehay; Prof.Gedif, Teferi
    Introduction: Self-medication is the first option and response to most illness episodes. Use of antimicrobials without health care professionals’ guidance may result in greater probability of inappropriate, missed diagnosis, delays in appropriate treatment, pathogen resistance and increased morbidity. There is no sector in the health care community which is immune to drug abuse or misuse of which the worst offenders include Physicians, Nurses and Pharmacists. Self-medication among health care professionals may be an indicator that the health professional is neglecting his or her own health. This is important because the health habits and attitudes of health care professionals influence the counseling and care they provide to patients. Objective: This study was conducted to assess the prevalence of self-medication practices of antibiotics and factors associated with it among health care professionals in selected hospitals of Addis Ababa. Methods: Cross-sectional survey using self-administered questionnaires was employed to collect information from health professionals working in hospitals which were selected by using simple random sampling method. Data were collected from April to May, 2017. Results: A total of 317 respondents participated in this study. The prevalence of self-medication using antibiotics among health care professionals in one month recall period was found to be 72 (22.7%). The main reasons given for this were being familiar with the treatment options 31 (37%) , to get quick relief 25 (30%), lack of time. Respiratory problems accounted for self-medication 29 (40.3%) followed by gastro intestinal problems 28 (38.9%) were the two most common perceived illnesses for self-medication with antibiotics. Penicillins 30 (42%) and Fluroquinolones 29 (40%) were the most commonly used antibiotics for self-medication. None of the variables had significant association with the practice of self-medication with antibiotics. Conclusions and Recommendations: Overall, the prevalence of self-medication using antibiotics among health care professionals was high, which might contribute for the increasing antibiotic resistance. Therefore, the regulatory body should strictly regulate the sale of antibiotics without prescription. Regular short term training for all health care professionals on antibiotic self-medication and the consequences of antimicrobial resistance should be done to curb these practices.
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    Anticoagulation Management Practice, and Associated Factors in Atrial Fibrillation Patients on Warfarin Therapy at Saint Paul Hospital Millennium Medical College
    (Addis Abeba University, 2021-05) Shiferaw, Nuredin; Umer, Shemsu (PhD, Assistant Professor); Assefa, Tamrat (Assistant Professor)
    Anticoagulants are cornerstones in management of Atrial Fibrillation to prevent stroke. Monitoring of warfarin depends on time in therapeutic range, frequency of international normalization range measurements, warfarin dose adjustments, warfarin drug interaction and bleeding adverse event. This study aimed to assess the anticoagulation management, and factors affecting anticoagulation management in atrial fibrillation patients taking warfarin. Institutionalbased Retrospective Cross-Sectional study was conducted from August to October 2019 at St. Paul Hospital Millennium Medical College. Data were collected retrospectively from a total of 300 patient medical records. Patients who have taken warfarin as an indication of primary prevention of atrial fibrillation were included in the study. A systematic random sampling technique was employed while recruiting the study participants. The data were entered to Statistical Package for Social Science window version 25 for analysis. Descriptive summaries were presented by using frequencies and percentages. Time in therapeutic range was calculated using the Rosendaal method, international normalization range frequency and drug interaction with warfarin were assessed and warfarin dose adjustments were also checked. Univariate and multivariate analysis were used to determine factors affecting time in therapeutic range and bleeding events. P-value ≤0.05 was considered as statistically significant. The mean age of the patient was 56.37 years and 65.3% of the study participants were females. Percent time in therapeutic range was found to be 42.03 ± 18.75. Only 12.67% patients had a time in the therapeutic range above 65%. Out of the 3162 INR tests, only 1094(34.60%) tests were within the therapeutic range. Bleeding event was recorded on 62 (20.70%) of the patients. Poor time in therapeutic range was associated with only age between 65 and 74, number of comedication of 1 and 2 and presence of congestive heart failure. Anticoagulation management was found to be poor in this study compared to other studies.
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    Anticonvulsant Effect of Pterlobium stellatum (Leaves), Moringa stenopetala (Root) And Clutia abyssinica (Leaves) Traditionally Used for Treatment of Epilepsy in Ethiopia Using Mice Model
    (Addis Ababa University, 2021-06) Sahile Salile, Samson (PhD); Prof. Abula, Teferra
    Background :Epilepsy is the third leading contributor to the global burden of disease for neurological disorders and affects 65 million people worldwide. Although the current antiepileptic drugs achieve symptomatic seizure relief they do not prevent or reverse the pathological process that underlies human epilepsy. Drug resistant epilepsy is also one of the most important unmet needs in the daily management of epilepsy. These currently unmet needs provide a roadmap for the development of more effective antiseizure drugs, as well as for disease modifying and antiepileptogenic drugs especially from plants. This study was conducted to investigate the anticonvulsant activity of the crude hydroalcoholic extracts of 3selected plants Pterlobium stellatum ( leaves), Moringa stenopetala (root) and Clutia abyssinica (leaves). These all are used for treatment of epilepsy by traditional healers in different parts of Ethiopia. Additionally the solvent fractions of the Pterlobium stellatum were tested for anticonvulsant activity as the crude extract showed positive response in all the models used. Methods :.The dry residues of the plant extracts were used for test in different doses. Male balb c mice were used for in vivo study and for in vitro study P14-P21 of C57BL16 mice were used. In vitro mice model of hippocampal slice with 0Mg 2+ was used and the extracts were tested at the 0.7mg/kg concentration. Diazepam 3µM was positive control and DMSO as negative control. In in vivo PTZ and MES mice models 400mg/kg and 800mg/kg of each test extract were used for efficacy test in as positive control Diazepam 5mg/kg and phenytoin 10mg/kg were used respectively. The negative control was 2% tween 80 .Fisher's exact test was used to analyze proportions and ANOVA with post hoc LSD to test means. The tests were conducted after the ethical clearance was obtained from the ethical committee of Addis Ababa University and university of Cape Town. Qualitative test and quantitative tests were used to determine the secondary metabolites in the plants. And ultraperformance liquid chromatography-mass spectrometer (UPLCMS) tests were used to characterize plant constituents in Pterlobium stellatum crude extract and its fractions. Results :In the in vitro study the hydroalcoholic extract of P.stellatumand M. stenopetalaat 0.7mg/ml had a statistically significant anticonvulsant activity compared to negative control(P<0.05). The hydroalcoholic extract of C.abyssinicaat 0.7mg/ml didn't show statistically significant effect compared to negative control (P>0.05). A positive control, diazepam(3µM), showed statistically significant anticonvulsant activity compared with negative control (P<0.05).When we compare the in vitro activity of different solvent fractions of P. stellatum,the chloroform and water fractions at 0.7mg/ml were also shown to have significant anticonvulsant activity as compared to negative control (P<0.05). The petether and butanol fractions activities were not statistically significant compared to negative control (P>0.05). Pterolobium stellatum hydroalcoholic extract shown that dose dependent and statistically significant anticonvulsant activity with PTZ model(P<0.05).Whereas the activity of M. stenopetala and C. abyssinica hydroalcoholic extracts were not statistically significant (P>0.05) in in vivo PTZ model. The in vivo PTZ test has also revealed the chloroform fraction and the water fraction of Pterolobium stellatum to have anticonvulsant effect(P<0.05) compared with the negative control. Whereas the pet ether and butanol fractions shown activity which was not statistically significant with negative control(P>0.05).The effect of the diazepam was statistically significant with the negative control and all test extracts (P<0.05). Pterolobium stellatum and M. stenopetala hydroalcoholic extracts shown statistically significant anticonvulsant activity with MES model in both lower and higher doses(P<0.05). The C. abyssinica hydroalcoholic extracts activity at the given doses were not statistically significant (P>0.05).The in vivo MES test has also revealed the chloroform fraction to have anticonvulsant effect at both doses (P<0.05). The water fraction at 400mg/kg dose shown anticonvulsant effect compared with the negative control(P<0.05). The pet ether and butanol fractions shown activity which was not statistically significant at the given doses (P>0.05).The effect of the phenytoin was statistically significant with the negative control as well as compared with other tested extract doses(P<0.05). The qualitative and quantitative analysis indicated the presence of different plant secondary metabolites in hydromethanolic extracts of the three plants. In Pterolobium stellatum the UPLCMS analysis indicated also the presence of gallic acid, ellagic acid, kaempferol, myricitrin, isoquercitrin and quercitirin in the crude extract. Of these gallic acid and ellagic acid were found in chloroform fraction. In the water fraction ellagic acid, kaempferol, myricitrin and isoquercitrin were found. Conclusion: The results demonstrated that Pterolobium stellatum has anticonvulsant effect. The hydroalcoholic and chloroform and water fraction of Pterolobium stellatum demonstrated effect in both in vitro and in vivo MES and PTZ models of epilepsy. The crude extract of Moringa stenopetala has also shown to have anticonvulsant effect both in the in vitro and in vivo MES models. But was negative on PTZ model. The traditional use of both herbs for treatment of epilepsy can be supported by the finding of this study. However ,C. abyssinica didn't show anticonvulsant activity at the tested doses in the models used in this study and its traditional use for treatment of epilepsy is not supported according to the findings of this study.
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    Anticonvulsant Activity of 80% Methanol Extract and Solvent Fractions of Ajuga integrifolia Buch.-Ham (Lamiaceae) leaves in Mice
    (Addis Abeba University, 2020-11) Getaneh, Yigrem; Abula, Teferra( Professor)
    Ajuga integrifolia is one of the species in the genus Ajuga that is used in the Ethiopian traditional medicine for the treatment of different ailments, including epilepsy. Thus, this study was initiated to evaluate the traditional anticonvulsant use of 80% methanol leaves extract and solvent fractions of Ajuga integrifolia. Acute routine screening tests; the pentylenetetrazole (PTZ) and maximal electroshock (MES) models were used. The rota rod test was further performed to evaluate neurotoxic effect of the plant. Swiss albino mice of 6-8 weeks old were randomly assigned to five groups (n=6/group). The test groups received 100, 200 and 400mg/kg oral dose of crude extract and solvent fractions for both PTZ and MES tests as well as 2.5, 5 and 10mg/kg i.p. dose for rota rod test. The positive control groups received valproate 200mg/kg oral for PTZ, phenytoin 25mg/kg oral for MES, and diazepam 5mg/kg i.p for rota rod test. The negative control groups received oral dose of 10 ml/kg of distilled water or 2% tween 80. The crude extract produced dose dependent and statistically significant anticonvulsant effect on both PTZ and MES induced seizures. It was suggested by delayed latency (p<0.001 for 400 mg/kg and p<0.05 for 100mg/kg and 200mg/kg) and fast recovery (p<0.001 for all doses) on PTZ and reduction of duration of tonic hind limb extension (p<0.001 for all doses) in MES model, against control. Similarly, n-butanol and chloroform fractions displayed dose dependent activity in both models as evidenced by having significant activity against control. However, aqueous fraction at doses used did not show a significant effect on latency and duration on both models. Furthermore, all doses of the crude extract and solvent fractions did not display a significant change in motor coordination. The plant extract contained alkaloid, glycosides, flavonoids, phenols, steroids, tannins, terpenoids and saponins that might contribute to the observed anticonvulsant activity. In conclusion, the plant has anticonvulsant activity at various doses providing evidence for its traditional use.
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    Anticonvulsant Activity of Soxhlet Leaf Extracts of Ajuga Integrifolia Buch.Ham ex D.Don (Lamiaceae) in Mice
    (Addis Ababa University, 2021-11) Desalegn, Tesfaye; Prof. Engidawork, Ephrem
    Epilepsy is one of the most common chronic neurological conditions that affect 70 million people in different parts of the world. The leaves of Ajuga integrifolia Buch.ham ex D Don have been used as anti-convulsant remedy in Ethiopian traditional medicine. However, the evidence supporting this claim is sparse in the literature. This study was conducted to add to the existing body of knowledge about the anti-convulsant activity of the plant. To this effect successive Soxhlet extraction was performed using n-hexane, ethyl acetate, methanol and water. Anti-convulsant activity of the extracts was investigated in both acute (pentylenetetrazole, PTZ; and maximal electroshock, MES) and chronic (PTZ kindling) seizure models. For the acute model, various doses of the extract (100mg/kg, 200mg/kg and 400mg/kg) were administered. Positive controls received sodium valproate (200mg/kg) for PTZ and phenytoin (25mg/kg) for MES. Distilled water or 2% tween 80 was used for negative controls. Kindling was induced by repeated alternate day intra-peritoneal administration of sub-convulsive dose of PTZ (35 mg/kg) for 13 days and the most active extract (ethyl acetate) was tested in this model. Parameters including onset of clonus and duration of hind limb tonic extension were recorded. Moreover, total alkaloid, flavonoid and phenol contents of the most active extract were determined. Treatment of mice with ethyl acetate extract produced a superior effect among all solvent extracts in both PTZ and MES model. The mean latency to clonic seizure was significantly increased (p<0.01) with all doses of ethyl acetate extract in PTZ test compared to control and n.hexane extract ranked next to ethyl acetate extract in increasing onset of clonus. It significantly increased mean onset of clonus compared to controls, with a maximum increase (12.67min, p<0.001) displayed by HA400 mg/kg. Methanol extract at 200mg/kg and 400 mg/kg also significantly delayed onset of clonus (p<0.001) in PTZ model.Once again, all doses of ethyl acetate extract of the study plant significantly reduced (p<0.001) the mean duration of hind limb tonic extension in MES test compared to control. Hexane extract at 200 mg/kg and 400 mg/kg also significantly reduced (p<0.001) duration of hind limb tonic extension. Methanol extract at 200mg/kg and 400 mg/kg also significantly reduced (p<0.01) mean duration of hind limb tonic extension (HLTE) compared to control in MES test. Aqueous extract at all doses was devoid of any anti-convulsant effect in both models. A similar type of study done on the leaf crude extract and solvent fractions collected from different geographical location also reported anti-convulsant activity of the plant in acute seizure models. Treatment of mice with 200mg/kg and 400mg/kg of ethyl acetate extract along with alternate day PTZ injection significantly protected(p<0.01 for 200mg/kg and p<0.001 for 400 mg/kg) against PTZ induced kindling compared to controls in chronic model. Ethyl acetate extract of the plant was found to contain 10.002±0.119 mg atropine equivalent per gram of dry extract of alkaloids, 9.045 ±0.8445 mg quercetin equivalent /g of dry weight extract of flavonoids and 21.928 ±1.118 mg gallic acid equivalent / g of dry weight of extract of phenols. This study indicated that the plant has anti-convulsant activity in both acute and chronic model and it could be a potential source to develop a new anti epileptic drug for pharmacoresistant epilepsy.
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    Antidepressant-like Activity of Solvent Fractions of the Root Bark of Carissa spinarum Linn. (Apocynaceae) in Rodents
    (Addis Ababa University, 2022-03) Saif, Hana; Prof. Engidawork, Ephrem
    Depression is a chronic and recurrent psychiatric disorder affecting mental and physical health. Traditional medicines have been used for decades in the treatment of depression due to resistance development, side effects, inadequate accessibility and affordability of modern antidepressant drugs. The root bark of Carissa spinarum Linn. (Apocynaceae), which is used traditionally for depression is reported to possess antidepressant- like activit y in rodent models of depression. In the current study, different fractions of the root bark obtained using solvents of different polarities were investigated using a host of models, including tail suspension test (TST), forced swim test (FST), muricidal behavioral test, and open field test (OFT). Moreover, markers for depression and phytoconstituents were determined, and preliminary mechanistic studies using different drugs were also conducted. Five groups of animals of either sex each having 6 animals per group were randomly assigned for every model and each solvent fraction (Ethyl acetate, n-butanol, and aqueous). Group I, served as a negative control group and received a vehicle (2% Tween 80), group II served as a positive control and received the standard drug Imipramine (30 mg/kg), group III-V received increasing doses of the solvent fractions 50, 100 and 200 mg/kg, respectively. Ethyl acetate (CSE) and n-butanol (CSB) fractions significantly (p<0.001) reduced the duration of immobility in TST and FST, while the aqueous fraction (CSA) failed to show any appreciable antidepressant- like activity. No change in the locomotor activity using OFT was observed at all doses. From the two active fractions, the ethyl acetate fraction was the most effective and contributed to reducing the muricidal behavior in rats. Serum corticosterone level was reduced by both fractions and once again the ethyl acetate fraction was the most effective. Mechanistic studies revealed the involvement of multiple neurotransmission systems, including adrenergic, dopaminergic and choline r gic as well as the L-Arginine-NO-cGMP pathway in the antidepressant- like effect of the plant, hence only both the dopaminergic and the L-Arginine-NO-cGMP pathway were the predominant by which the ethyl acetate fraction might mediate its action. Phytochemica l analysis showed the presence of high content of alkaloids (0.17 mgATE/g and 0.07 mgATE/g), flavonoids (12.43 mgQE/g and 2.07 mgQE/g), and phenols (42.42 mgGAE/g and 29.8 mgGAE/g) for CSE and CSB, respectively. The findings collectively indicate that CSE and CSB are endowed with antidepressant- like activity due to the presence of phenols, flavonoids, and alkaloids, which are medium polar in nature.
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    Antidiarrheal Activity of Aqueous and 80% Methanol Extracts of the Leaves of Leucas Abyssinica (Lamiaceae) in Mice
    (Addis Abeba University, 2020-11) Abera, Tadele; Abula, Teferra( Professor)
    Leucas abyssinica (Lamiaceae family) is one of the medicinal plants used for the management of diarrhea in Ethiopia but it lacks scientific evidence. Thus, this study was aimed to evaluate the antidiarrheal activities of aqueous and 80% methanol extracts of the leaves of Leucas abyssinica using experimental models in mice. castor oil induced diarrhea, misoprostol induced enteropooling, normal and castor oil induced gastrointestinal transit in mice models were used to evaluate antidiarrheal activity of the plant. Five groups of mice (six animals per group) were used for each model. These groups were negative control group (received distilled water 10 ml/kg), positive control group (administered loperamide 3 mg/kg) and three test groups (treated with graded dose of 100, 200 and 400 mg/kg aqueous and methanol 80% extracts respectively). Pretreatment of mice with stated doses of both extracts of the plant significantly reduced the frequency of wet and total feces, the weight of wet and total feces as well as increased diarrheal free periods compared to negative controls. Both extracts produced significant reduction in both the weight and volume of intestinal contents induced by misoprostol in a dose dependent manner. The percentage of inhibition of gastrointestinal transit induced by castor oil for both extracts were significant (p < 0.001) at all the tested doses in a dose dependent fashion. But none of the tested doses of both extracts significantly reduced normal gastrointestinal transit in mice. Finally, the results from this study suggests that both extracts of the plant have significant antidiarrheal effect on animal models and this finding supports the antidiarrheal traditional use of the plant for management of diarrhea.
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    Antidiarrheal Activity of Crude Extract and Coumarins from Psydrax schim- periana (A. Rich.) Bridson. Roots in Swiss Albino Mice, and Evaluation of Nu- tritional Composition and Anti-nutritional Factors of Its Fruits
    (Addis Ababa University, 2023) Damissie,Getahun; Hymete,Ariaya(PhD); Tadesse,Solomon (PhD); Tolossa,Ketema (PhD)
    Despite considerable improvements in the accessibility of medical services, diarrheal illnesses continue to claim the lives of children, accounting for up to 9% of all pediatric fatalities world- wide. The roots of Psydrax schimperiana is traditionally used to treat diarrhea and its fruits are consumed for nutritional purposes in Ethiopia. This study aimed to investigate in vivo antidiar- rheal activity of crude extract and coumarins isolated from the roots of P. schimperiana to pro- vide a pharmacological basis for its traditional use as diarrhea agent and to evaluate the nutri- tional composition and anti-nutritional factors from its fruits. Maceration with 80% methanol was used to prepare the crude extract from the powdered roots of P. schimperiana. The crude roots extract of P. schimperiana was tested for in vivo antidiarrheal efficacy in mice utilizing castor oil-induced diarrhea, gastrointestinal transit time and enteropool- ing models at doses of 100, 200, and 400 mg/kg. Phytochemical investigation of the crude roots extract led to the isolation of two coumarins, isoscopoletin and scoparone. The structures of these compounds were established by interpretation of their spectral data, and by comparison with data reported in the literature. Isoscopoletin and scoparone were evaluated for antidiarrheal activity against castor oil-induced diarrhea model at 10 mg/kg and 20 mg/kg doses. Moisture content, ash value, crude protein, crude fibers, crude fat, phytate, tannin, and oxalate contents of P. schimperiana fruits were determined according to the standard analytical proce- dure. All generated data were analyzed using SPSS software version 26. The crude root extract of P. schimperiana, at doses of 100, 200, and 400 mg/kg, inhibited defe- cation by 37.5%, 46.2%, and 61.2%, respectively. At a dose of 20 mg/kg, scoparone and isosco- poletin reduced defecation by 61.2% and 66.6%, respectively. ii Fruits from P. schimperiana contained 31% fiber, 9.19% crude protein, 12.40% moisture, 6.38% ash, and 0.99% fat. The fruits also contained the anti-nutritional factors phytate (1.16%), oxalate (0.72%), and tannin (22.96%). The study provides a scientific basis for further development and usage of the roots of P. schimperiana, and warrants continued investigation of isoscopoletin and scoparone toward development as a novel treatment for diarrheal diseases. The fruits of P. schimperiana can be considered as a beneficial source of vital nutrients such as carbohydrate, protein, and crude fibers. However, the higher tannin content may interfere with the absorption of essential minerals and inhibit effective utilization of proteins