Acute and subacute toxicity profile of ethanolic stem bark extract of Albizia coriaria Welw. ex Oliv. in Wistar albino rats.

Albizia coriaria (Fabaceae) crude extracts are key ingredients of several licensed and unlicensed herbal products in East Africa. However, there is limited and often contradicting information regarding its toxicity. We therefore evaluated the acute and subacute toxicity of the ethanolic stem bark extract of A. coriaria in mature healthy Wistar albino rats following Lorke's method and OECD guidelines 407. The LD50 of the ethanolic stem bark extract of A. coriaria was 2000 mg/kg. The acute toxicity signs observed included piloerection, hyperventilation, lethargy, and loss of righting reflex. There was a significant increase in aspartate aminotransferase, alkaline phosphatase, red blood cells and haemoglobin in rats after 28 days at the dose of 500 mg/kg. Histological analyses revealed multifocal random parenchymal necrosis and scattered periportal mononuclear inflammatory cells infiltration in the liver, interstitial nephritis in the kidney and multifocal lymphoid accumulation in the peribronchiolar and perivascular lung tissue at 500 mg/kg. The ethanolic stem bark of A. coriaria was therefore moderately toxic to the rats when administered in a single high oral dose within 24 h. The extract caused a dose dependent toxicity with significant damage to the kidney, liver and lung tissues at a dose of 500 mg/kg after 28 days. Herbal medicines containing A. coriaria extracts should be consumed cautiously due to likelihood of toxicity particularly at higher doses greater than 500 mg/kg.

Ethnobotanical survey and phytochemistry of medicinal plants used in the management of HIV/AIDS in Eastern Uganda.

Currently, highly active antiretroviral therapy is unable to cure HIV/AIDS because of HIV latency. This study aimed at documenting medicinal plants used in the management of HIV/AIDS in Eastern Uganda so as to identify phytochemicals with HIV latency reversing potential. An ethnobotanical survey was conducted across eight districts in Eastern Uganda. Traditional medicine practitioners were interviewed using semi-structured questionnaires. Qualitative and quantitative phytochemical tests were respectively, performed to determine the presence and quantity of phytochemicals in frequently mentioned plant species. Data were analysed and presented using descriptive statistics and Informant Consensus Factor (ICF). Twenty-one plant species from fourteen plant families were reported to be used in the management of HIV/AIDS. Six plant species with the highest frequency of mention were: Zanthoxylum chalybeum, Gymnosporia senegalensis, Warbugia ugandensis, Leonatis nepetifolia, Croton macrostachyus and Rhoicissus tridentata. Qualitative phytochemical analysis of all the six most frequently mentioned plant species revealed the presence of flavonoids, tannins, terpenoids, alkaloids and phenolics. Quantitative analysis revealed the highest content of flavonoids in L. nepetifolia (20.4 mg/g of dry extract) while the lowest content was determined in C. macrostachyus (7.1 mg/g of dry extract). On the other hand, the highest content of tannins was observed in L. nepetifolia. (199.9 mg/g of dry extract) while the lowest content was found in R. tridentata. (42.6 mg/g of dry extract). Medicinal plants used by traditional medicine practitioners in Eastern Uganda to manage HIV/AIDS are rich in phytochemicals including flavonoids and tannins. Further studies to evaluate the HIV-1 latency reversing ability of these phytochemicals are recommended to discover novel molecules against HIV/AIDS.

Assessing the protective effect of Crassocephalum vitellinum against Rifampicin-induced hepatotoxicity in Wistar rats.

Background: Crassocephalum vitellinum is widely used by traditional medical practitioners and local people in East Africa to manage a large number of ailments including hepatitis 1. However, its hepatoprotective effects had not been evaluated prior to this study. The aim of this study was to assess the effect of an ethanolic leaf extract of Crassocephalum vitellinum against rifampicin-induced liver toxicity in Wistar rats. Methods: Increasing doses of an ethanolic leaf extract of C. vitellinum were administered to Wistar rats daily for 35 days, together with rifampicin given orally as suspension. After the treatment period, Assessment of hepatoprotective activity was done by analysis of serum levels of biochemical and histopathological effects on the liver. Results: The results showed that administration of C. vitellinum extract significantly prevented drug- induced increase in serum levels of liver biomarker enzymes and also decreased the hepatocellular necrosis and inflammatory cells infiltration. Conclusion: The plant extract loweres the liver biomarker enzymes (ALT, ALP, AST) and preserves the histomorphology of the hepatocytes which is suggestive that the plant possess hepatoprotective properties.

Are antibiotic prescription practices in Eastern Uganda concordant with the national standard treatment guidelines? A cross-sectional retrospective study.

OBJECTIVES: This study aimed to evaluate the antibiotic prescription patterns of health workers in Eastern Uganda and more specifically whether they are in accordance with the Ugandan standard treatment guidelines and other indicators of appropriate antimicrobial prescription. METHODS: Patient data were obtained from the health management information system of the outpatient department registers of Soroti and Mbale Regional Referral Hospitals from 2016-2018. RESULTS: The prevalence of non-adherence to treatment guidelines when prescribing antibiotics was 82.6% (95% CI 81.4-83.7%). Guidelines were more likely to be adhered to when prescribing antibiotics for individuals aged 13-19 years compared with their counterparts aged 0-12 years [adjusted odds ratio (aOR) = 0.55, 95% CI 0.40-0.74]. When prescribing antibiotics for males, health workers were twice as likely not to adhere to guidelines compared with when prescribing for females (aOR = 2.09, 95% CI 1.61-2.72). When prescribing cephalosporins and nitroimidazoles, health workers were likely not to adhere to guidelines compared with when prescribing penicillin (cephalosporins, aOR = 1.92, 95% CI 1.28-2.86; nitroimidazoles, aOR = 1.70, 95% CI 1.09-2.65). Health workers were most likely not to follow guidelines when prescribing antibiotics in combination (two antibiotics, aOR = 1.27, 95% CI 1.03-1.56). CONCLUSION: Non-adherence to treatment guidelines for an indicated diagnosis and inappropriate antibiotic prescription are significantly prevalent in Eastern Uganda. Health workers were more likely not to follow guidelines when prescribing for males, children up to 12 years of age and when prescribing cephalosporins, nitroimidazoles or double antibiotic combinations.

Antimicrobial resistance and rational use of medicine: knowledge, perceptions, and training of clinical health professions students in Uganda.

BACKGROUND: Antimicrobial resistance (AMR) is an important global health concern, projected to contribute to significant mortality, particularly in developing countries. This study aimed to determine the knowledge, perceptions of clinical health professions students towards antimicrobial resistance and rational use of medicine and confidence level to prescribe antimicrobials. METHODS: An online descriptive cross-sectional survey was conducted among clinical health professions students across 9 medical schools in Uganda. A semi-structured questionnaire using Kobo Toolbox form was shared among participants via WhatsApp Messenger (Meta, California, USA). Knowledge was categorized using modified Bloom's cut-off. One-way ANOVA, Chi-square or Fisher's exact test, and logistic regression were used to assess the association between dependent and independent variables. A p < 0.05 was considered statistically significant. RESULTS: We surveyed 681 participants, most were pursuing a Bachelor of Medicine and Surgery degree (n = 433, 63.6%), with a mean age of 24 (standard deviation: 3.6) years. Most participants (n = 596, 87.5%) had sufficient knowledge about antimicrobial resistance with a mean score of 85 ± 14.2%. There was a significant difference in mean knowledge scores of year 4 (86.6%) compared to year 3 (82.4%) (p = 0.002) and year 5 (88.0%) compared to year 3 (82.4%) (p < 0.001). Most participants (n = 456, 66.9%), were confident on making an accurate diagnosis of infection, and choosing the correct antimicrobial agent to use (n = 484, 71.1%). CONCLUSION: Health profession students exhibited good knowledge on antimicrobial resistance and high self-perceived confidence that should be leveraged to foster better future antimicrobial prescription practices. However, they still agreed that a separated course unit on AMR is necessary which responsible authorities should consider to consolidate the efforts.

Sub-Acute Toxicity Effects of Methanolic Stem Bark Extract of Entada abyssinica on Biochemical, Haematological and Histopathological Parameters in Wistar Albino Rats.

Background: Whereas the efficacy of Entada abyssinica (fabaceae) extracts against various ailments has been scientifically validated, its safety has not been established. This study was undertaken to evaluate the toxicity effects of methanolic stem bark extract of E. abyssinica on biochemical, haematological and histological parameters of Wistar albino rats following repeated oral administration. Methods: Wistar albino rats of both sexes were randomized into groups and orally administered daily with determined doses (150, 300 and 600 mg/kg) of E. abyssinica methanolic extract using 1% tween 80 in distilled water as a control for 28 days. On the 29th day, all the animals were sacrificed and dissected to collect blood and selected organs. The serum and whole blood were assayed for biochemical and haematological parameters respectively while selected organs were examined for histopathological lesions. Numerical data was analyzed using graph pad prism and expressed as mean ± standard error of mean. The differences between the treatment and control groups were tested for statistical significance using one-way analysis of variance and/or Student's t-test. Results: In repeated daily oral doses (150, 300 and 600 mg/kg), the methanolic stem bark extract of E. abyssinica did not cause significant alteration in majority of the biochemical and hematological indices. However, the extract significantly elevated the level of uric acid (all doses), aspartate aminotransferase (300 and 600 mg/kg), low density lipoproteins (150 mg/kg) and mean corpuscular heamoglobin concentration (all doses). On the other hand, the extracts reduced high density lipoproteins (150 and 300 mg/kg), mean corpuscular volume (all doses), haematocrit (150 and 600 mg/kg), mean platelet volume (150 and 600 mg/kg) and procalcitonin (150 mg/kg). In the vital organs, there were no significant lesions observed except at the highest dose (600 mg/kg) where there was mild evidence of lymphocyte infiltration in the liver and focal interstitial nephritis. Conclusion: The methanolic stem bark extract of E. abyssinica is relatively safe in Wistar albino rats when repetitively administered orally in small doses for a prolonged period of time. We recommend more chronic toxicity studies and clinical trials on herbal remedies containing this plant to ensure that its use is free of potential toxicity to humans.

Appropriateness and affordability of prescriptions to diabetic patients attending a tertiary hospital in Eastern Uganda: A retrospective cross-sectional study.

BACKGROUND: Irrational prescription of drugs can lead to high cost of treatment thus limiting access to essential medicines. We assessed the affordability and appropriateness of prescriptions written for diabetic patients in Eastern Uganda. METHODS: We collected secondary data from the health management information system registers of patients who attended the outpatient medical clinic at Mbale regional referral hospital from January 2019 to December 2019. The average cost of the prescriptions was calculated and adjusted odds ratios for predictors for unaffordability estimated using logistic regression. Computed scores for indicators of rational drug prescription were used to assess the extent of rational prescribing. RESULTS: The median cost per prescription was USD 11.34 (IQR 8.1, 20.2). Majority of the diabetic patients (n = 2462; 94.3%, 95% CI: 93.3-95.1%) could not afford the prescribed drugs. Predictors for unaffordability were if a prescription contained: ≥ 4 medicines (AOR = 12.45; 95% CI: 3.9-39.7); an injectable (AOR = 5.47; 95%CI: 1.47-20.32) and a diagnosis of diabetes mellitus with other comorbidities (AOR = 3.36; 95%CI: 1.95-5.78). Having no antidiabetic drug prescribed was protective for non-affordability (AOR = 0.38; 95%CI: 0.24-0.61). The average number of drugs per prescription was 2.8. The percentage prescription of drugs by generic name and from the essential medicine and health supplies list of Uganda were (6160/7461; 82.6%, 96% CI: 81.7%-83.4%) and (6092/7461; 81.7%, 95% CI: 80.8%-82.5%) respectively against WHO standard of 100%. CONCLUSION: The majority of diabetic patients (94.3%) in Eastern Uganda cannot afford to buy prescribed medicines. The government should therefore ensure that essential medicines are readily accessible in public health facilities.

Prevalence of antibiotic-resistant bacteria among patients in two tertiary hospitals in Eastern Uganda.

OBJECTIVE: The aim of this study was to determine the prevalence and antibiotic resistance patterns of bacterial isolates from inpatients and outpatients in Mbale and Soroti regional referral hospitals in Eastern Uganda. METHODS: A retrospective analysis of culture and antibiotic sensitivity test results from the microbiology laboratories of the two tertiary hospitals was conducted for a 3-year period (January 2016-December 2018). RESULTS: Microbiology records of 3092 patients were reviewed and analysed, with 1305 (42.1%) samples yielding clinical isolates. The most prevalent isolates were Escherichia coli (n = 442; 33.9%), Staphylococcus aureus (n = 376; 28.8%), Klebsiella pneumoniae (n = 237; 18.2%), and Streptococcus pneumoniae (n = 76; 5.8%). High rates of antimicrobial resistance were detected across both Gram-negative and Gram-positive bacteria. Escherichia coli and K. pneumoniae were resistant to several agents such as amoxicillin/clavulanate (83.5%; 64.6%), cefotaxime (74.2%; 52.7%), ciprofloxacin (92.1%; 27.8%), gentamicin (51.8%; 76%), imipenem (3.2%; 10.5%), tetracycline (98%; 74.5%), and trimethoprim-sulfamethoxazole (74.1%; 74.3%), respectively. Staphylococcus aureus and S. pneumoniae exhibited the following resistance profile: cefoxitin (44.4%; 40.9%), chloramphenicol (69.1%; 27.6%) clindamycin (21.5%; 24.4%), gentamicin (83.2%; 66.9%), penicillin (46.5%; -) tetracycline (85.6%; 97.6%), trimethoprim-sulfamethoxazole (88%; 91.3%), and vancomycin (41.2%; -). CONCLUSION: We observed high resistance rates to antibiotics among the majority of microorganisms that were isolated from the samples collected from patients in Eastern Uganda. Furthermore, measures should be undertaken locally to improve microbiology diagnostics and to prevent the spread of antibiotic-resistant strains as this impedes the optimal treatment of bacterial infections and narrows the choice of effective therapeutic options.

A Descriptive-Multivariate Analysis of Community Knowledge, Confidence, and Trust in COVID-19 Clinical Trials among Healthcare Workers in Uganda.

Background-misinformation and mistrust often undermines community vaccine uptake, yet information in rural communities, especially of developing countries, is scarce. This study aimed to identify major challenges associated with coronavirus disease 2019 (COVID-19) vaccine clinical trials among healthcare workers and staff in Uganda. Methods-a rapid exploratory survey was conducted over 5 weeks among 260 respondents (66% male) from healthcare centers across the country using an online questionnaire. Twenty-seven questions assessed knowledge, confidence, and trust scores on COVID-19 vaccine clinical trials from participants in 46 districts in Uganda. Results-we found low levels of knowledge (i.e., confusing COVID-19 with Ebola) with males being more informed than females (OR = 1.5, 95% CI: 0.7-3.0), and mistrust associated with policy decisions to promote herbal treatments in Uganda and the rushed international clinical trials, highlighting challenges for the upcoming Oxford-AstraZeneca vaccinations. Knowledge, confidence and trust scores were higher among the least educated (certificate vs. bachelor degree holders). We also found a high level of skepticism and possible community resistance to DNA recombinant vaccines, such as the Oxford-AstraZeneca vaccine. Preference for herbal treatments (38/260; 14.6%, 95% CI: 10.7-19.3) currently being promoted by the Ugandan government raises major policy concerns. High fear and mistrust for COVID-19 vaccine clinical trials was more common among wealthier participants and more affluent regions of the country. Conclusion-our study found that knowledge, confidence, and trust in COVID-19 vaccines was low among healthcare workers in Uganda, especially those with higher wealth and educational status. There is a need to increase transparency and inclusive participation to address these issues before new trials of COVID-19 vaccines are initiated.