The Role of Pharmacogenomics Studies for Precision Medicine Among Ethiopian Patients and Their Clinical Implications: A Scoping Review.

Background: Pharmacogenomics research is currently revolutionizing treatment optimization by discovering molecular markers. Medicines are the cornerstone of treatment for both acute and chronic diseases. Pharmacogenomics associated treatment response varies from 20% to 95%, resulting in from lack of efficacy to serious toxicity. Pharmacogenomics has emerged as a useful tool for therapy optimization and plays a bigger role in clinical care going forward. However, in Africa, in particular in Ethiopia, such studies are scanty and not generalizing. Therefore, the objective of this review was to outline such studies, generating comprehensive evidence and identify studied variants' association with treatment responses in Ethiopian patients. Methods: The Joanna Briggs Institute's updated 2020 methodological guidelines for conducting and guidance for scoping reviews were used. We meticulously adhered to the systemic review reporting items checklist and scoping review meta-analyses extension. Results: Two hundred twenty-nine possibly relevant studies were searched. These include: 64, 54, 21, 48 and 42 from PubMed, Scopus, Google Scholar, EMBASE, and manual search, respectively. Seventy-seven duplicate studies were removed. Thirty-nine papers were rejected with justification, whereas 58 studies were qualified for full-text screening. Finally 19 studies were examined. The primary pharmacogene that was found to have a significant influence on the pharmacokinetics of efavirenz was CYP2B6. Drug-induced liver injury has frequently identified toxicity among studied medications. Conclusion and Future Perspectives: Pharmacogenomics studies in Ethiopian populations are less abundant. The studies conducted focused on infectious diseases, specifically on HAART commonly efavirenz and backbone first-line anti-tuberculosis drugs. There is a high need for further pharmacogenomics research to verify the discrepancies among the studies and for guiding precision medicine. Systematic review and meta-analysis are also recommended for pooled effects of different parameters in pharmacogenomics studies.

Leishmaniases in Ethiopia: a scoping review protocol to determine the scope of research and remaining gaps.

INTRODUCTION: The leishmaniases are among the group of neglected tropical diseases that cause significant morbidity and mortality each year. Currently, the East Africa region has the highest visceral leishmaniasis burden in the world. Ethiopia is one of the East African countries that reports both visceral and cutaneous forms of the disease. As part of the Nairobi Declaration, Ethiopia showed commitment to the elimination of visceral leishmaniasis by 2030. In this endeavour, it is important to understand the scope of research conducted on leishmaniases in the country and identify where the research gaps exist. Determining the research landscape is vital in the plan towards leishmaniases control and elimination. It will help to reference conducted research, determine if systematic reviews are warranted and help prioritise future research directions. METHODS AND ANALYSIS: This protocol was developed with reference to the JBI Scoping Review Methodology Group's guidance on conducting scoping reviews and the PRISMA-ScR reporting guidelines for scoping reviews. The following databases will be searched: PubMed, Embase via Embase.com, Web of Science Core Collection, Cochrane CENTRAL, Global Index Medicus, ClinicalTrials.gov, the Pan African Clinical Trials Registry and PROSPERO. Locally published literature that may not be indexed in the above-mentioned systems will be identified through team members familiar with the setting. Each record will be dually and blindly reviewed in an abstract-title screen and full-text screen using inclusion-exclusion criteria. Included articles must contain an in-depth discussion of leishmaniasis in Ethiopia. Data extracted will consist of study themes, study types, and categories and subcategories each defined in the developed codebook, in addition to type of leishmania, year of publication, funding source and the number of citations. Results will be reported with summary statistics. ETHICS AND DISSEMINATION: Individual consenting and ethical approvals are not applicable. We plan to disseminate our findings to the appropriate stakeholders.

Prevalence of risky sexual behavior and associated factors among Injibara University students, Northwest Ethiopia.

Introduction: Engaging in risky sexual behaviors can lead to HIV infection, sexually transmitted infections, and unintended pregnancy among youths. University students had greater sexual risks for many reasons. Therefore, this study aimed to assess the magnitude and associated factors of risky sexual behaviors among regular undergraduate students at Injibara University, Northwest Ethiopia. Methods: A cross-sectional study was conducted at Injibara University from 20 January to 30 2020. Multistage sampling was employed to select 770 students. Data were collected using a semistructured self-administered questionnaire. A binary logistic regression model was used to identify factors associated with risky sexual behavior. Adjusted odds ratios with 95% CIs were determined, and variables with P-values <0.05 were considered significant. Result: A total of 770 students participated in the study, providing a response rate of 100%. In this study, 294 (38%, 95% CI: 35%, 42%) students engaged in risky sexual behaviors. Risky sexual behavior was significantly associated with not tested for HIV (AOR = 1.62, 95% CI: 1.15-2.31), peer pressure (AOR = 1.90, CI: 1.37-2.64), basic HIV knowledge (AOR = 2.16, CI: 1.65-2.89), substance use (AOR = 3.56, CI: 2.11-6.06), watching pornography videos (AOR = 1.58, CI: 1.11-2.23), and HIV risk perception (AOR = 1.37, CI: 1.02-1.91). Conclusion and recommendation: A substantial proportion of university students in this study engaged in unsafe sexual behavior. Risky sexual behaviors are more likely to occur when students are under peer pressure, use substances, have no perceived HIV risk, watch pornography, and have inadequate basic HIV knowledge. Therefore, tailored strategic interventions such as life skill training should be designed to bring about positive behavioral changes among university students.

First report of cutaneous leishmaniasis caused by Leishmania donovani in Ethiopia.

BACKGROUND: Leishmaniasis is a common neglected tropical disease in Ethiopia. Visceral leishmaniasis (VL) caused by Leishmania donovani presents in the lowlands, while cutaneous leishmaniasis (CL) affects people living in the highlands. Although CL is described as being caused by Leishmania aethiopica, there is also evidence of L. tropica and L. major isolated from a patient, sand flies and potential reservoirs. Information on species causing CL in Ethiopia is patchy, and no nation-wide study has ever been done. Understanding which species are causing CL in Ethiopia can have important implications for patient management and disease prevention. METHODS: We analyzed stored routine samples and biobanked DNA isolates from previously conducted studies of CL patients from different centers in the north, center and south of Ethiopia. Species typing was performed using ITS-1 PCR with high-resolution melt (HRM) analysis, followed by HSP70 amplicon sequencing on a selection of the samples. Additionally, sociodemographic, clinical and laboratory data of patients were analyzed. RESULTS: Of the 226 CL samples collected, the Leishmania species could be determined for 105 (45.5%). Leishmania aethiopica was identified in 101 (96.2%) samples from across the country. In four samples originating from Amhara region, northwestern Ethiopia, L. donovani was identified by ITS-1 HRM PCR, of which two were confirmed with HSP70 sequences. While none of these four patients had symptoms of VL, two originated from known VL endemic areas. CONCLUSIONS: The majority of CL was caused by L. aethiopica, but CL due to L. tropica and L. major cannot be ruled out. Our study is the first to our knowledge to demonstrate CL patients caused by L. donovani in Ethiopia. This should spark future research to investigate where, how and to which extent such transmission takes place, how it differs genetically from L. donovani causing VL and whether such patients can be diagnosed and treated successfully with the currently available tools and drugs.

Obstructive sleep apnea risk and determinant factors among type 2 diabetes mellitus patients at the chronic illness clinic of the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.

Introduction: Obstructive sleep apnea is a sleep complaint among type 2 diabetes mellitus patients that has a deleterious effect on health with immediate and long-term impacts. Despite its impacts, data on the magnitude and predictors of obstructive sleep apnea among type 2 diabetes mellitus patients in Ethiopia is still limited. Thus, this study was conducted to determine how common a high risk of obstructive sleep apnea is and its predictors among type 2 diabetes mellitus patients receiving follow-up care at the chronic illness follow-up clinic at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia, 2022. Methods: An institution-based cross-sectional study was conducted. Interviewer-administered questionnaires and physical measurements with standard instruments were used to collect the required data. The collected data were entered into EpiData 4.6 and exported into STATA 14. Both Bivariable and multivariable binary logistic regression analyses were done to identify factors associated with a high risk of obstructive sleep apnea. Variables with a p-value ≤0.05 in the multivariable logistic regression analysis were declared as significantly associated with a high risk of obstructive sleep apnea. Results: A total of 319 type 2 diabetes mellitus patients with a median age of 58 years participated in our current study. The overall prevalence of a high risk of obstructive sleep apnea among the study participants was 31.97% (95%CI: 27.06, 37.32). On multivariable logistic analysis, a neck circumference of ≥40 cm (AOR=4.33, 95%CI 1.37, 13.72), physical inactivity (AOR=2.29, 95%CI 1.15, 4.53), comorbid hypertension (AOR=4.52, 95%CI 2.30, 9.18), and male sex (AOR=8.01, 95%CI 3.02, 21.24) were associated with a high risk of obstructive sleep apnea. Conclusion and recommendation: The prevalence of a high risk of obstructive sleep apnea among type 2 diabetes mellitus patients remains high. A neck circumference of ≥40 cm, physical inactivity, comorbid hypertension, and male sex were significantly associated with a high risk of obstructive sleep apnea among type 2 diabetes mellitus patients. Screening and evaluation of type 2 diabetes mellitus patients for obstructive sleep apnea are recommended to avoid the negative impacts.

Efficacy, Safety, Tolerability, and Pharmacokinetics of MMV390048 in Acute Uncomplicated Malaria.

An open label, phase IIa study conducted in Ethiopia evaluated the efficacy, safety, tolerability, and pharmacokinetics of a single 120-mg dose of the phosphatidylinositol 4-kinase inhibitor MMV390048 in Plasmodium vivax malaria. The study was not completed for operational reasons and emerging teratotoxicity data. For the eight adult male patients enrolled, adequate clinical and parasitological response at day 14 (primary endpoint) was 100% (8/8). Asexual parasites and gametocytes were cleared in all patients by 66 and 78 hours postdose, respectively. There were two recurrent P. vivax infections (days 20 and 28) and a new Plasmodium falciparum infection (day 22). MMV390048 exposure in P. vivax patients was lower than previously observed for healthy volunteers. Mild adverse events, mainly headache and gastrointestinal symptoms, were reported by eight patients. Single-dose MMV390048 (120 mg) rapidly cleared asexual parasites and gametocytes in patients with P. vivax malaria and was well tolerated.

Determinants of post-stroke depression among stroke survivors at University of Gondar Hospital, Northwest Ethiopia: a case-control study.

BACKGROUND: Stroke is one of the most common causes of disability among adults. Post-stroke depression (PSD) is a frequent neuropsychiatric complication in stroke patients. Despite the increasing prevalence of stroke, there is a paucity of data on PSD and its determinants among stroke survivors in developing countries like Ethiopia. We aim to assess the factors associated with PSD in survivors of stroke. METHOD: A hospital-based unmatched case-control study was conducted during the period of February to July 2020 at University of Gondar Hospital among stroke survivors. Study subjects were recruited consecutively. Socio-demographic and clinical data were obtained from patients' interviews and medical record reviews. A diagnosis of PSD was made using the Patient Health Questionnaire (PHQ-9). EpiData version 3.1 was used to enter data, and SPSS version 26 was used to analyze it. Bivariate and multivariate logistic regressions were fitted to identify associated variables. The adjusted odds ratio (AOR) with 95% confidence interval (CI) and p-value 0.05 were used to determine the significance of the association. RESULT: A total of 240 stroke survivors were included in the study (80 cases and 160 controls). The mean age was 60.8 years (SD ± 14.3) with an equal sex distribution. Variables statistically associated with PSD were male gender (AOR = 3.5, 95% CI: 1.64-7.46 C, P-value = 0.001), subcortical location of the largest lesion (AOR = 2.42, 95% CI: 1.06-5.56, p-value = 0.036), severity of the stroke (AOR = 52.34, 95% CI:10.64-256.87, p-value = 0.000), physical disability (AOR = 5.85. 95% CI:1.94-17.65, p-value = 0.002), previous history of stroke or transient ischemic attack (AOR = 5.90, 95% CI:2.04-17.10, p-value = 0.001) and ischemic heart disease (AOR = 9.97, 95% CI:3.4-29.22, p-value = 0.000). CONCLUSION: Important factors in the occurrence of PSD in this study include prior history of stroke, physical disability, severity of the stroke, subcortical location of the lesion, male gender, and ischemic heart disease. Stroke patients with such factors need routine screening for PSD, particularly in LMICs where there is uncoordinated post-stroke care, a shortage of neurologists and mental health practitioners.

Renal outcomes of diabetic patients treated with combination therapy of ACE inhibitors plus either thiazide diuretics or calcium channel blockers: comparative retrospective cohort study in Northwestern Ethiopia.

OBJECTIVE: The study determined the comparative renal functions on patients with diabetes treated with ACE inhibitors (ACEIs) plus either thiazide diuretics or calcium channel blockers (CCBs) in Northwestern Ethiopia. DESIGN: Retrospective cohort study design was employed to collect the data from medical records of patients with diabetes followed for 1-5 years (N=404). SETTING: The medical records of patients in chronic diabetic follow-up clinics of the hospital. PARTICIPANTS: All the patients with diabetes medical records in Northwestern Ethiopian specialised hospital. MAIN OUTCOME MEASURES: Exposures were ACEIs plus thiazide diuretics or CCBs collected from March to June 2020. Outcomes were defined as declining in estimated glomerular filtration rate (eGFR) values by ≥30% from the baseline recorded from 2015 to 2019. Descriptive and analytical statistics were illustrated to compare the study groups. Kaplan-Meier with log- rank test was used to plot the survival analyses curve. Potential factors substantially associated to renal events were examined using cox proportional hazards model. RESULT: About 20% of patients developed renal events and significant numbers were from hydrochlorothiazide (HCT) users. The mean eGFR levels were significantly higher in patients on CCBs users over the follow-up years compared with HCT-based users. The CCBs users had an 18.8 mL/min/1.73 m2 higher in eGFR levels at the end of the follow-up period than HCT users (p<0.001). HCT users had shorter survival probability overtime to develop the outcomes compared with CCBs users (p=0.003). The CCBs-based regimen prevented risks of declining in renal function by 56.4% than HCT (p=0.001). Hazards of declining in eGFR levels were 93% higher for the patients with initial systolic blood pressure (SBP) levels were more than 150 mm Hg (p=0.006). CONCLUSION: Compared with HCT, patients on CCBs had significantly prevented risks of renal events. However, both groups appeared with the same cardiovascular events. HCT-based regimen and higher initial SBP levels were significantly associated with eGFR reductions.

One-Third of Perinatal Women Living with HIV Had Perinatal Depression in Gondar Town Health Facilities, Northwest Ethiopia.

BACKGROUND: Depression is the most common co-morbidity among perinatal women living with HIV. It affects client's adherence to care and treatment, which results in increased viral load; further exposing women to opportunistic infections that reduce quality-of-life. A cumulative effect of these may increase mother-to-child transmission of HIV. METHODS: An institution-based cross-sectional study was conducted among perinatal women living with HIV in Gondar town health facilities, Northwest Ethiopia from October 1-30, 2018. A single population proportion formula was used to calculate the sample size. The sample was stratified and proportionally allocated to each health facility. Participants were chosen from each stratum independently using a simple random sampling technique. A total of 422 study participants were selected. The World Health Organization (WHO) 20-item self-reported questionnaire (SRQ-20) was used to measure perinatal depression among women living with HIV. Perceived stigma was measured using HIV stigma scale. Women were interviewed at the PMTCT clinic during follow-up care, and clinical variables were extracted from client chart. Bi-variable and multivariable logistic regression models were used to identify factors associated with perinatal depression. Variables having an odds ratio with 95% confidence interval and a P-value less than 0.05 were taken as significant variables associated with perinatal depression. RESULTS: The prevalence of perinatal depression among women living with HIV was found to be 38.4% (95% CI=34.1-43.1%). Fair and poor ART drug adherence (AOR=5.44; 95% CI= 2.81-10.56%), the presence of comorbid illness (AOR=3.24; 95% CI: 1.83-5.75), being on second line ART (AOR=2.97; 95% CI=1.08-8.17), perceived stigma (AOR=3.61; 95% CI=2.11-6.17), and suicidal ideation (AOR=3.89; 95% CI=1.28-11.81) were factors associated with perinatal depression. CONCLUSION: The prevalence of perinatal depression among women living with HIV was found to be high. Adherence counseling needs to be strengthened; preventing first line treatment failure has to be encouraged; greater emphasis has to be given for those women on second line ART. Early identification and management of co-morbidity has to be considered. HIV positive perinatal women need counseling to reduce HIV-related perceived stigma.