Accuracy of non-invasive diagnosis of esophageal varices among cirrhotic patients in a low-income setting.

Cirrhosis is a chronic liver disease that is frequently complicated by increased portal venous pressure and the formation of EV. The most common clinical manifestation of portal hypertension is esophageal varices, and ruptured varices are the most fatal complication of portal hypertension. The diagnosis and follow-up of esophageal varices is done by Esophagogastroduodenoscopy, but in most developing countries, the follow-up of cirrhotic patients by gastrointestinal endoscopy remains a challenge. Objective: Assessment of diagnostic accuracy of noninvasive tests as predictors of esophageal varices among cirrhotic patients at University of Gondar comprehensive Hospital. Method: Institution based cross-sectional study was conducted among cirrhotic patients from March 2022-October 2022. All study participants underwent screening for Esophageal Varices, Spleen Diameter, Platelet count and Platelet count/spleen diameter ratio. Data were analyzed using SPSS version 26. ROC curves were plotted for Spleen Diameter, Platelet count and Platelet count/spleen diameter ratio with specific cutoffs determined. Diagnostic performance was assessed using ROC curve. The diagnostic thresholds were specified with their sensitivity, specificity, positive predictive value, negative predictive value positive and negative likelihood ratios. Result: A total of 206 patients were included. The mean age was 41.84 year and SD of (41.84 ± 12.398). About 79.4 % percent were males. Endoscopy confirmed esophageal varices were present in 176(85.4 %) cases. Sixty-seven percent of cases had decompensated cirrhosis (Child-Pugh class B&C). The platelet count to spleen diameter ratio less than 818 had a PPV of 94.7 % (AUROC = 0.835), while spleen diameter greater than 145 mm had 93.7 % PPV (AUROC = 0.783). At a platelet count cutoff <121,000/mm3, the PPV was 95.1 % (AUROC = 0.818). Conclusion: In this study, platelet count, spleen diameter, and PC/SD all performed well for EV diagnostics, with PC/SD outperforming the others. This finding supports the use of these noninvasive indicators for the diagnosis and implementation of prophylactic treatment foe esophageal varices in health institutions where gastrointestinal endoscopy is unavailable.

Clinical and individual factors of quality of life of chronic liver disease patients at University of Gondar comprehensive specialized hospital, Northwest Ethiopia 2022.

Chronic liver disease (CLD) may be a major cause of morbidity and mortality worldwide, as well as a reduction in health-related quality of life. In Ethiopia, however, little is known about the effect of CLD on quality of life. The purpose of this study was to evaluate CLD patients' health-related quality of life and associated factors. A cross-sectional study was carried out on 227 CLD patients who were being followed up on at the University of Gondar specialized hospital between January 2022 and February 2022. To assess health-related quality of life, the chronic disease Questionnaire was used. Epi-Data version 4.6 was used to enter data, and SPSS version 25 was used for all statistical analysis. To identify factors associated with the outcome variable, a linear regression model was used. Patients with CLD had significantly lower mean scores in all domains of health-related quality of life. Hepatitis B virus treatments and a college education or higher have a positive effect on all domains of health-related quality of life. Upper gastrointestinal bleeding, spontaneous bacterial peritonitis (SBP), hepatic encephalopathy (HE), and ascites were a clinical related factors significantly associated with poor health-related quality of life in simple linear regression. In this study setting, all dimensions of health-related quality of life of patients with CLD were compromised. Antiviral treatment for HBV infection, beta-blocker treatment, and the presence of complications such as ascites were all found to be significantly related to health-related quality of life. This necessitates going above and beyond standard treatments to improve patients' quality of life with CLD.

Attitude, Perceived Barriers, and Challenges Toward Implementing Resource-Appropriate Guidelines for Hematologic Malignancies: Physicians' Survey in Ethiopia.

PURPOSE: Cancer care in low-income countries poses formidable challenges. Care may be facilitated by resource-adapted guidelines, such as the National Comprehensive Cancer Network (NCCN) harmonized guidelines for sub-Saharan Africa (NCCN-HG). Understanding physicians' attitudes and knowledge toward guidelines, as well as patient- and resource-related barriers, is essential for promoting their effective implementation. METHODS: We conducted an online survey among oncologists, hematologists, internists, residents/fellows, and generalists treating hematologic malignancies in Ethiopia. We assessed attitudes toward the use of guidelines, institutional capacity, and barriers/determinants to effective care. RESULTS: Among the 47 physicians completing the survey (representing 64% of Ethiopian professionals treating hematologic malignancies), the majority (85%) reported using guidelines; however, only 22.7% (n = 10) used the NCCN-HG. While overall attitudes toward guidelines were favorable, 57.8% of physicians familiar with the NCCN-HG were either undecided or believed that it lowers the standard of care. Perceived lack of institutional regulation was negatively associated with guideline use (B = -3.23; P = .004). Lack of diagnostic facilities including immunohistochemistry and flow cytometry, supportive care, and poor utilization of guidelines were reported to be determinants of poor patient outcome. Regarding patient factors, 57.4% respondents identified treatment abandonment as an important contributor to poor outcome. Availability of chemotherapy/radiotherapy (89.4%), financial status (85.1%), distance from the hospital (74.5%), and harvest season (65%) had major influences on treatment decisions. Over 80% reported that targeted therapies were unavailable or rarely available. CONCLUSION: Awareness and usage of the NCCN-HG are limited among Ethiopian physicians. Lack of facilities, therapies, and regulation, in addition to patient-related factors, was identified as barriers to guideline adherence and determinants of poor outcome.

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.

Prevalence and antimicrobial resistance pattern of Clostridium difficile among hospitalized diarrheal patients: A systematic review and meta-analysis.

BACKGROUND: Clostridium difficile is the leading cause of infectious diarrhea that develops in patients after hospitalization during antibiotic administration. It has also become a big issue in community-acquired diarrhea. The emergence of hypervirulent strains of C. difficile poses a major problem in hospital-associated diarrhea outbreaks and it is difficult to treat. The antimicrobial resistance in C. difficile has worsened due to the inappropriate use of broad-spectrum antibiotics including cephalosporins, clindamycin, tetracycline, and fluoroquinolones together with the emergence of hypervirulent strains. OBJECTIVE: To estimate the pooled prevalence and antimicrobial resistance pattern of C. difficile derived from hospitalized diarrheal patients, a systematic review and meta-analysis was performed. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed to review published studies conducted. We searched bibliographic databases from PubMed, Scopus, Google Scholar, and Cochrane Library for studies on the prevalence and antimicrobial susceptibility testing on C. difficile. The weighted pooled prevalence and resistance for each antimicrobial agent was calculated using a random-effects model. A funnel plot and Egger's regression test were used to see publication bias. RESULTS: A total of 15 studies were included. Ten articles for prevalence study and 5 additional studies for antimicrobial susceptibility testing of C. difficile were included. A total of 1967/7852 (25%) C. difficile were isolated from 10 included studies for prevalence study. The overall weighted pooled proportion (WPP) of C. difficile was 30% (95% CI: 10.0-49.0; p<0.001). The analysis showed substantial heterogeneity among studies (Cochran's test = 7038.73, I2 = 99.87%; p<0.001). The weighed pooled antimicrobial resistance (WPR) were: vancomycin 3%(95% CI: 1.0-4.0, p<0.001); metronidazole 5%(95% CI: 3.0-7.0, p<0.001); clindamycin 61%(95% CI: 52.0-69.0, p<0.001); moxifloxacin 42%(95% CI: 29-54, p<0.001); tetracycline 35%(95% CI: 22-49, p<0.001); erythromycin 61%(95% CI: 48-75, p<0.001) and ciprofloxacin 64%(95% CI: 48-80; p< 0.001) using the random effect model. CONCLUSIONS: A higher weighted pooled prevalence of C. difficile was observed. It needs a great deal of attention to decrease the prevailing prevalence. The resistance of C. difficile to metronidazole and vancomycin was low compared to other drugs used to treat C. difficile infection. Periodic antimicrobial resistance monitoring is vital for appropriate therapy of C. difficile infection.

Hyperglycemia After Dolutegravir-Based Antiretroviral Therapy.

BACKGROUND: Antiretroviral therapies prolong life expectancy and improve the quality of life of HIV-infected patients. Despite the documented benefits of antiretroviral drugs, its use is not without side effects. Here, we report cases of new onset diabetes mellitus after taking a dolutegravir (DTG)-based ART regimen. CASE PRESENTATION: HIV-infected patients who had been on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART regimens for more than a decade were shifted to integrase strand transfer inhibitors (dolutegravir)-based ART regimen as recommended by the National Comprehensive HIV Care Guideline. They were diagnosed to have diabetes mellitus with or without diabetic ketoacidosis (DKA) as evidenced by polyuria, polydipsia and fatigue, severe hyperglycemia (plasma glucose level >250 mg/dl) with or without ketonuria (3+) after 1-12 months of DTG-based ART regimen. Two of the patients who presented with DKA were treated with intravenous fluids and regular insulin. NPH insulin was started following recovery from DKA, which later shifted to metformin. One of the patients who presented with severe hyperglycemia without DKA was started with NPH insulin, which later shifted to metformin. Good glycemic control was obtained with metformin, while the DTG-based ART regimen was continued. CONCLUSION: Hyperglycemia is a potential and noticed side effect of the DTG-based ART regimen. Baseline and periodic monitoring of plasma glucose might be required in ART regimens containing dolutegravir.

Acute kidney injury in patients with Visceral Leishmaniasis in Northwest Ethiopia.

BACKGROUND: Visceral Leishmaniasis (VL) is a neglected tropical disease endemic to several countries including Ethiopia. Outside of Africa, kidney involvement in VL is frequent and associated with increased mortality. There is however limited data on acute kidney injury (AKI) in VL patients in East-Africa, particularly in areas with high rates of HIV co-infection. This study aims to determine the prevalence, characteristics and associated factors of AKI in VL patients in Northwest Ethiopia. METHODS: A hospital based retrospective patient record analysis was conducted including patients treated for VL from January 2019 to December 2019 at the Leishmaniasis Research and Treatment Center (LRTC), Gondar, Ethiopia. Patients that were enrolled in ongoing clinical trials at the study site and those with significant incomplete data were excluded. Data was analyzed using SPSS version 20. P values were considered significant if < 0.05. RESULTS: Among 352 VL patients treated at LRTC during the study period, 298 were included in the study. All were male patients except two; the median age was 23 years (IQR: 20-27). The overall prevalence of AKI among VL patients was 17.4% (confidence interval (CI): 13.6%-22.2%). Pre-renal azotemia (57%) and drug-induced AKI (50%) were the main etiologies of AKI at admission and post-admission respectively. Proteinuria and hematuria occurred in 85% and 42% of AKI patients respectively. Multivariate logistic regression revealed HIV co-infection (adjusted odds ratio (AOR): 6.01 95% CI: 1.99-18.27, p = 0.001) and other concomitant infections (AOR: 3.44 95% CI: 1.37-8.65, p = 0.009) to be independently associated with AKI. CONCLUSION: AKI is a frequent complication in Ethiopian VL patients. Other renal manifestations included proteinuria, hematuria, and pyuria. HIV co-infection and other concomitant infections were significantly associated with AKI. Further studies are needed to quantify proteinuria and evaluate the influence of AKI on the treatment course, morbidity and mortality in VL patients.

Geographical Variability in Paromomycin Pharmacokinetics Does Not Explain Efficacy Differences between Eastern African and Indian Visceral Leishmaniasis Patients.

INTRODUCTION: Intramuscular paromomycin monotherapy to treat visceral leishmaniasis (VL) has been shown to be effective for Indian patients, while a similar regimen resulted in lower efficacy in Eastern Africa, which could be related to differences in paromomycin pharmacokinetics. METHODS: Pharmacokinetic data were available from two randomized controlled trials in VL patients from Eastern Africa and India. African patients received intramuscular paromomycin monotherapy (20 mg/kg for 21 days) or combination therapy (15 mg/kg for 17 days) with sodium stibogluconate. Indian patients received paromomycin monotherapy (15 mg/kg for 21 days). A population pharmacokinetic model was developed for paromomycin in Eastern African and Indian VL patients. RESULTS: Seventy-four African patients (388 observations) and 528 Indian patients (1321 observations) were included in this pharmacokinetic analysis. A one-compartment model with first-order kinetics of absorption and elimination best described paromomycin in plasma. Bioavailability (relative standard error) was 1.17 (5.18%) times higher in Kenyan and Sudanese patients, and 2.46 (24.5%) times higher in Ethiopian patients, compared with Indian patients. Ethiopian patients had an approximately fourfold slower absorption rate constant of 0.446 h-1 (18.2%). Area under the plasma concentration-time curve for 24 h at steady-state (AUCτ,SS) for 15 mg/kg/day (median [interquartile range]) was higher in Kenya and Sudan (172.7 µg·h/mL [145.9-214.3]) and Ethiopia (230.1 µg·h/mL [146.3-591.2]) compared with India (97.26 µg·h/mL [80.83-123.4]). CONCLUSION: The developed model provides detailed insight into the pharmacokinetic differences among Eastern African countries and India, however the resulting differences in paromomycin exposure do not seem to explain the geographical differences in paromomycin efficacy in the treatment of VL patients.

Compliance, Barriers, and Facilitators to Social Distancing Measures for Prevention of Coronavirus Disease 2019 in Northwest Ethiopia, 2020.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is the defining global health crisis of our time. To date, there is no curative treatment for COVID-19, and with vaccines only recently being rolled out predominantly in wealthy countries, prevention still remains the main strategy. Social distancing has been proven to mitigate the epidemic and limit disease spread. As is the case in many other countries, the Ethiopian government has declared a state of emergency and taken several measures to impose social distancing. The level of compliance with social distancing measures in Ethiopia is unknown. OBJECTIVE: The aim of this study was to assess the compliance, barriers, and facilitators to social distancing measures for the prevention of COVID-19 in Northwest Ethiopia. METHODS: A cross-sectional survey using telephone interview triangulated by a qualitative study was conducted over a period of 1 month from April 20 to May 20, 2020, at the University of Gondar Hospital in Gondar, Ethiopia. A total of 401 randomly selected participants, and 12 key representative informants selected by convenience were included for the quantitative and qualitative studies, respectively. Information on sociodemographic factors, knowledge about COVID-19, and practices concerning preventive measures--particularly social distancing--was collected. Respondents were asked what they believed were the barriers and facilitators of social distancing during in-depth face-to-face interviews. Data were entered and analyzed using Epi-data and Stata software, respectively. Frequencies and odds ratios were analyzed. P values < 0.05 were considered statistically significant, and a confidence level of 95% strength of association was used. RESULTS: A total of 425 potential participants were approached and 401 responded positively (response rate = 94.4%). Of the 401 study participants, 55.4% (95% CI, 50.4%-60.2%) reported poor compliance with social distancing measures. The mean (SD) age of participants was 36.4 (11.8) years. The majority of participants (63.84%) reported that they went to crowded places without putting on a face mask. Of the participants, 243 (60.6%) and 306 (76.3%) had good knowledge of COVID-19 transmission and prevention, respectively. Multivariate logistic regression analysis revealed that only age (adjusted odds ratio = 1.02; 95% CI, 1.00-1.04) was significantly associated with social distancing measures, with older persons more likely than younger to comply with social distancing guidelines. CONCLUSIONS: The majority of the study's participants reported poor compliance with social distancing measures set by the government and health authorities for prevention of COVID-19. Reported compliance with social distancing measures increased with increasing age. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX) © 2021 Elsevier HS Journals, Inc.

The prevalence and predictors of Stroke among atrial fibrillation patients attending at Gondar University Referral Hospital, Northwest Ethiopia.

INTRODUCTION: Recently, stroke is becoming the major public health problem in developing countries including Ethiopia. Atrial fibrillation patients are the most vulnerable group for the occurrence of stroke. Knowing the predictors and being aware for it is important for preventing severe complications and death. Therefore, the aim of this study is to assess the prevalence of stroke and identifying significant predictors. METHODS: A hospital-based cross-sectional study was performed from 1 December 2018 to 30 September 2019 at University of Gondar Referral Hospital. A total of 242 patients with atrial fibrillation were included in the study. Atrial fibrillation patients were diagnosed by using 12 lead electrocardiographic tracing, in addition to thorough medical history and physical examination and analyzed by the Modular ECG Analysis System (MEANS). We used Epi info 7 and SPSS version 22 software for data entry and analysis purpose, respectively. Both bivariable and multivariable binary logistic regression model were computed to show the relationship of dependent and independent variables. RESULT: The prevalence of stroke among atrial fibrillation patients was 19.4% (95% confidence interval (CI): 14.9-25.2). Patients with heart failure (adjusted odds ratio (AOR): 5.70, 95% CI: 2.50-13.24) and thyroid disorder (AOR: 4.98, 95% CI: 1.47-16.85) are at risk of developing stroke. CONCLUSION: The prevalence of stroke was higher compared with others studies. Patients with heart failure and thyroid disorders were the risk factor for the development of stroke; therefore, physicians and cardiologists may better to consider all these two disorders when they diagnose stroke in patients with atrial fibrillation.

HIV Co-Infection Among Presumptive Tuberculosis Cases and Asthmatic Patients at University of Gondar Hospital, Northwest Ethiopia.

BACKGROUND: Tuberculosis and Human Immunodeficiency Virus (HIV) have been closely linked since the emergence of Acquired Immunodeficiency Syndrome (AIDS). Several studies have suggested an increased incidence of asthma among HIV positive individuals. This study aimed to determine the prevalence of Mycobacterium tuberculosis (MTB) and HIV infection among presumptive tuberculosis cases and asthmatic patients. METHODS: A hospital-based, cross-sectional study was conducted on 424 study participants from October 2018 - June 2019. Sociodemographic data and sputum samples were collected and investigated by Ziehl-Neelsen microscopy, Gene Xpert MTB/RIF assay, and culture. The nutritional status of the patients was assessed by body mass index. Finally, data was entered, cleared, and checked using Epi-info version 7 and exported to SPSS version 20 for analysis. Logistic regression was used for statistical association. p-value < 0.05 at 95% CI was considered statistically significant. RESULTS: The overall prevalence of MTB and HIV infection was 3.86% and 5.4%, respectively. The prevalence of MTB infection among presumptive tuberculosis (TB) cases was 4.4%, but none among asthmatic patients. The prevalence of HIV infection among presumptive TB cases and asthmatic patients was 5.2% and 6.6%, respectively. The overall prevalence of malnutrition was 30%. The prevalence of malnutrition among culture-positive TB patients was 31.25% and that of HIV positive cases was 43.5%. The proportion of MTB infection among HIV positive patients was 12.5%. Marital status of the study subjects significantly associated with culture positive MTB infection. Occupation and previous history of tuberculosis infection had a statistically significant association with HIV infection. CONCLUSIONS: This study showed a high prevalence of HIV among asthmatic patients compared to presumptive TB cases. So, regular large-scale surveys should be conducted to assess the burden and intervene accordingly.

"Sell an Ox" - The Price of Cure for Hepatitis C in Two Countries.

Chronic hepatitis C virus (HCV) infection, associated with severe liver disease and cancer, affects 70 million people worldwide. New treatments with direct-acting-antivirals offer cure for about 95% of affected individuals; however, treatment costs may be prohibitive in both the poorest and richest nations. Opting for cure may require sacrificing essential household assets. We highlight the financial dilemmas involved, drawing parallels between Ethiopia and the United States, countries where universal health coverage does not yet exist. The World Health Organization (WHO) declaration for HCV eradication by 2030 will only become reality if universal access to efficacious and affordable treatment is guaranteed for everyone.

Prevalence of Chronic Kidney Disease and Associated Factors among Patients with Diabetes in Northwest Ethiopia: A Hospital-Based Cross-Sectional Study.

BACKGROUND: Chronic kidney disease (CKD) is increasingly recognized as a global health issue and it affects 10% to 15% of the world population. Diabetes mellitus is the leading cause of end-stage renal disease. More than 422 million adults in the world populations are living with diabetes mellitus, 40% of whom will develop CKD. CKD in diabetes increases the risk of early death and cardiovascular morbidity and mortality. There is a paucity of published data on the prevalence of CKD and its associated factors among patients with diabetes in northwest Ethiopia. OBJECTIVE: The aim of this study is to determine the prevalence and factors associated with CKD among patients with diabetes at University of Gondar Hospital, Northwest Ethiopia. METHODS: A hospital-based cross-sectional study was conducted from April 2 to July 31, 2018. Using convenience sampling, a total of 272 consecutive patients with diabetes were recruited for the study. Data regarding the patients' sociodemographic information, clinical characteristics, and laboratory parameters were collected using patient interview and review of medical records. Serum creatinine was measured and used to calculate estimated glomerular filtration rate using modification of diet in renal disease and chronic kidney disease epidemiology equations. Data were analyzed using SPSS version 20. Bivariate and multivariate logistic regression analyses were used to identify predictors of CKD in patients with diabetes. RESULT: The prevalence of CKD, defined by estimated glomerular filtration rate <60 mL/min/1.73 m2, was found to be 17.3% and 14.3% by modification of diet in renal disease and chronic kidney disease epidemiology equations, respectively. The proportion of stage 3 CKD by modification of diet in renal disease equation was 14.7%, whereas the proportions of stage 4 and stage 5 CKD were 2.2% and 0.4%, respectively. Among those who were diagnosed with CKD, 85.1% had pre-existing hypertension. Multivariate logistic regression analysis revealed that the presence of retinopathy (adjusted odds ratio = 14; 95% CI, 4-36; p < 0.001), pre-existing hypertension (adjusted odds ratio = 8.2; 95% CI, 2-23; P < 0.001), current systolic blood pressure >140 mm Hg (adjusted odds ratio = 6; 95% CI, 4-22; P = 0.001), and duration of diabetes >10 years (adjusted odds ratio = 3.2; 95% CI, 2-7; P = 0.004) were significantly associated with CKD in patients with diabetes. CONCLUSIONS: The prevalence of CKD in patients with diabetes is high and comparable with previous studies from low- and middle-income countries. Pre-existing hypertension, current systolic blood pressure >140 mm Hg, duration of diabetes >10 years, and presence of retinopathy were significantly associated with CKD. Regular screening for CKD, retinopathy, and optimal blood pressure management should be practiced.

Prevalence Of Anemia And Its Associated Factors Among Chronic Kidney Disease Patients At University Of Gondar Hospital, Northwest Ethiopia: A Hospital-Based Cross Sectional Study.

BACKGROUND: Chronic kidney disease (CKD) is a global public health problem associated with progressive decline in kidney function and adverse cardiovascular outcome. Anemia of CKD has substantial adverse outcomes in CKD patients. There is paucity of published data on prevalence of anemia and its associated factors among CKD patients in Northwest Ethiopia. OBJECTIVE: This study aimed to determine the prevalence of anemia and its associated factors among CKD patients at the University of Gondar hospital, Northwest Ethiopia. METHODS: A hospital-based cross-sectional study was conducted from May 1, to September 30, 2018. Consecutive sampling was used to recruit 251 study subjects. Patients were interviewed to obtain demographic data, and the patients' medical records were reviewed to obtain information on relevant medical history and laboratory parameters. Data was analyzed using SPSS version 20. Bivariate and multivariate logistic regression analyses were used to identify independently associated factors of anemia among CKD patients. P-value <0.05 was used to declare association. RESULTS: The overall prevalence of anemia in CKD patients was high (64.5%), and the magnitude worsened as kidney function declined. Hypertension (45%), chronic glomerulonephritis (24%) and diabetes (20%) were common causes of CKD. Multivariate logistic regression analysis revealed rural residence (AOR= 2.75, 95%CI: 1.34-5.65, P=0.006), BMI <18.5 kg/m2 (AOR=6.78, 95%CI: 1.32-34.73, P=0.022) and BMI of 18.5-24.9 kg/m2 (AOR=5.04, 95%CI: 1.26-20.10, P=0.022), and having hemodialysis history (AOR=3.59, 95%CI: 1.24-10.38, P=0.018) were independently associated with anemia among CKD patients. CONCLUSION: Periodic screening and intervention programs for anemia of CKD should be practiced to change the existing situation in the setting.

High Mortality from Blood Stream Infection in Addis Ababa, Ethiopia, Is Due to Antimicrobial Resistance.

BACKGROUND: Managing blood stream infection in Africa is hampered by lack of bacteriological support needed for antimicrobial stewardship, and background data needed for empirical treatment. A combined pro- and retrospective approach was used to overcome thresholds in clinical research in Africa. METHODS: Outcome and characteristics including age, HIV infection, pancytopenia and bacteriological results were studied in 292 adult patients with two or more SIRS criteria using univariate and confirming multivariate logistic regression models. Expected randomly distributed resistance covariation was compared with observed co-resistance among gram-negative enteric bacteria in 92 paediatric blood culture isolates that had been harvested in the same hospital during the same period of time. RESULTS: Mortality was fivefold increased among patients with positive blood culture results [50.0% vs. 9.8%; OR 11.24 (4.38-25.88), p < 0.0001], and for this group of patients mortality was significantly associated with antimicrobial resistance [OR 23.28 (3.3-164.4), p = 0.002]. All 11 patients with Enterobacteriaceae resistant to 3rd. generation cephalosporins died. Eighty-nine patients had pancytopenia grade 3-4. Among patients with negative blood culture results, mortality was significantly associated with pancytopenia [OR 3.12 (1.32-7.39), p = 0.01]. HIV positivity was not associated with increased mortality. Antimicrobial resistance that concerned gram-negative enteric bacteria, regardless of species, was characterized by co-resistance between third generation cephalosporins, gentamicin, chloramphenicol, and co-trimoxazole. CONCLUSION: Mortality was strongly associated with growth of bacteria resistant to empirical treatment, and these patients were dead or dying when bacteriological reports arrived. Because of co-resistance, alternative efficient antibiotics would not have been available in Ethiopia for 8/11 Enterobacteriaceae-infected patients with isolates resistant to third generation cephalosporins. Strong and significant resistance covariation between 3rd. generation cephalosporins, chloramphenicol, gentamicin, and co-trimoxazole was identified. Pronounced pancytopenia was common and associated with increased mortality. HIV positive patients had no excess mortality.

Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial.

BACKGROUND: Anti-leishmanial drug regimens that include a single dose AmBisome could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown. METHODOLOGY: A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1-5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT) PCR. PRINCIPAL FINDINGS: The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73-93%), 40% (95%CI 19-64%), and 58% (95%CI 41-73%) in patients treated with multiple doses (n = 63), and single doses of 7·5 (n = 21) or 10 mg/kg (n = 40), respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label. CONCLUSIONS: The tested AmBisome regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified. TRIALS REGISTRATION: www.clinicaltrials.govNCT00832208.

Arginase activity - a marker of disease status in patients with visceral leishmaniasis in ethiopia.

The underlying mechanisms resulting in the profound immune suppression characteristic of human visceral leishmaniasis (VL) are not fully understood. Here, we tested the hypothesis that arginase, an enzyme associated with immunosuppression, is higher in patients with VL and contributes to impaired T cell responses. We recruited patients with VL before and after treatment and healthy controls and measured the arginase metabolism in the blood of these individuals. Our results show that arginase activity is significantly higher in the blood of patients with active VL as compared to controls. These high levels of arginase decline considerably once the patients are successfully treated. We identified the phenotype of arginase-expressing cells among PBMCs as neutrophils and show that their frequency was increased in PBMCs of patients before treatment; this coincides with reduced levels of L-arginine in the plasma and decreased expression levels of CD3ζ in T cells.

Polymorphism in the HASPB repeat region of East African Leishmania donovani strains.

BACKGROUND/OBJECTIVES: Visceral leishmaniasis (VL) caused by Leishmania donovani is a major health problem in Ethiopia. Parasites in disparate regions are transmitted by different vectors, and cluster in distinctive genotypes. Recently isolated strains from VL and HIV-VL co-infected patients in north and south Ethiopia were characterized as part of a longitudinal study on VL transmission. METHODOLOGY/PRINCIPAL FINDINGS: Sixty-three L. donovani strains were examined by polymerase chain reaction (PCR) targeting three regions: internal transcribed spacer 1 (ITS1), cysteine protease B (cpb), and HASPB (k26). ITS1- and cpb--PCR identified these strains as L. donovani. Interestingly, the k26--PCR amplicon size varied depending on the patient's geographic origin. Most strains from northwestern Ethiopia (36/40) produced a 290 bp product with a minority (4/40) giving a 410 bp amplicon. All of the latter strains were isolated from patients with HIV-VL co-infections, while the former group contained both VL and HIV-VL co-infected patients. Almost all the strains (20/23) from southwestern Ethiopia produced a 450 bp amplicon with smaller products (290 or 360 bp) only observed for three strains. Sudanese strains produced amplicons identical (290 bp) to those found in northwestern Ethiopia; while Kenyan strains gave larger PCR products (500 and 650 bp). High-resolution melt (HRM) analysis distinguished the different PCR products. Sequence analysis showed that the k26 repeat region in L. donovani is comprised of polymorphic 13 and 14 amino acid motifs. The 13 amino acid peptide motifs, prevalent in L. donovani, are rare in L. infantum. The number and order of the repeats in L. donovani varies between geographic regions. CONCLUSIONS/SIGNIFICANCE: HASPB repeat region (k26) shows considerable polymorphism among L. donovani strains from different regions in East Africa. This should be taken into account when designing diagnostic assays and vaccines based on this antigen.

Arginase activity in the blood of patients with visceral leishmaniasis and HIV infection.

BACKGROUND: Visceral leishmaniasis is a parasitic disease associated with high mortality. The most important foci of visceral leishmaniasis in Ethiopia are in the Northwest and are predominantly associated with high rates of HIV co-infection. Co-infection of visceral leishmaniasis patients with HIV results in higher mortality, treatment failure and relapse. We have previously shown that arginase, an enzyme associated with immunosuppression, was increased in patients with visceral leishmaniasis and in HIV seropositive patients; further our results showed that high arginase activity is a marker of disease severity. Here, we tested the hypothesis that increased arginase activities associated with visceral leishmaniasis and HIV infections synergize in patients co-infected with both pathogens. METHODOLOGY/PRINCIPAL FINDINGS: We recruited a cohort of patients with visceral leishmaniasis and a cohort of patients with visceral leishmaniasis and HIV infection from Gondar, Northwest Ethiopia, and recorded and compared their clinical data. Further, we measured the levels of arginase activity in the blood of these patients and identified the phenotype of arginase-expressing cells. Our results show that CD4(+) T cell counts were significantly lower and the parasite load in the spleen was significantly higher in co-infected patients. Moreover, our results demonstrate that arginase activity was significantly higher in peripheral blood mononuclear cells and plasma of co-infected patients. Finally, we identified the cells-expressing arginase in the PBMCs as low-density granulocytes. CONCLUSION: Our results suggest that increased arginase might contribute to the poor disease outcome characteristic of patients with visceral leishmaniasis and HIV co-infection.

Sodium stibogluconate (SSG) & paromomycin combination compared to SSG for visceral leishmaniasis in East Africa: a randomised controlled trial.

BACKGROUND: Alternative treatments for visceral leishmaniasis (VL) are required in East Africa. Paromomycin sulphate (PM) has been shown to be efficacious for VL treatment in India. METHODS: A multi-centre randomized-controlled trial (RCT) to compare efficacy and safety of PM (20 mg/kg/day for 21 days) and PM plus sodium stibogluconate (SSG) combination (PM, 15 mg/kg/day and SSG, 20 mg/kg/day for 17 days) with SSG (20 mg/kg/day for 30 days) for treatment of VL in East Africa. Patients aged 4-60 years with parasitologically confirmed VL were enrolled, excluding patients with contraindications. Primary and secondary efficacy outcomes were parasite clearance at 6-months follow-up and end of treatment, respectively. Safety was assessed mainly using adverse event (AE) data. FINDINGS: The PM versus SSG comparison enrolled 205 patients per arm with primary efficacy data available for 198 and 200 patients respectively. The SSG & PM versus SSG comparison enrolled 381 and 386 patients per arm respectively, with primary efficacy data available for 359 patients per arm. In Intention-to-Treat complete-case analyses, the efficacy of PM was significantly lower than SSG (84.3% versus 94.1%, difference = 9.7%, 95% confidence interval, CI: 3.6 to 15.7%, p = 0.002). The efficacy of SSG & PM was comparable to SSG (91.4% versus 93.9%, difference = 2.5%, 95% CI: -1.3 to 6.3%, p = 0.198). End of treatment efficacy results were very similar. There were no apparent differences in the safety profile of the three treatment regimens. CONCLUSION: The 17 day SSG & PM combination treatment had a good safety profile and was similar in efficacy to the standard 30 day SSG treatment, suggesting suitability for VL treatment in East Africa. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.govNCT00255567.