Association of the Reduced Function Met420del Polymorphism of SLC22A1 with Metformin-Induced Gastrointestinal Intolerance in Ethiopian Patients with Type 2 Diabetes Mellitus.

Background: Despite its widespread use and favored profile, there are extensive variations in the treatment outcome of metformin therapy. Furthermore, studies reported that the inter-individual variability in the occurrence of metformin treatment associated side effects were related to the differences in individual genetic profiles. Thus, this study aimed to evaluate whether the reduced function methionine deletion at codon 420 (Met420del) variant of SLC22A1 (rs72552763) is associated with metformin induced gastrointestinal intolerance in Ethiopian patients with type 2 diabetes mellitus (T2DM). Patients and Methods: A retrospective observational study was conducted on 47 T2DM patients on metformin treatment for <3 years to assess the association of SLC22A1 (rs72552763) polymorphism with metformin induced gastrointestinal intolerance. Accordingly, 24 metformin tolerant and 23 metformin intolerant individuals with T2DM were recruited. Genotyping of rs72552763 was performed using TaqMan® Drug Metabolism Enzyme Genotyping Assay and its association to metformin induced gastrointestinal intolerance was assessed based on switching to a new class of glucose lowering agents or failure to up titrate dose due to metformin induced gastrointestinal intolerance. Chi-square, logistic regression and Mann-Whitney statistical tests were used as appropriate. Statistical significance was set at p < 0.05. Results: In our study, no significant association was observed between rs72552763 and metformin induced gastrointestinal intolerance. We found that the female gender and physical inactivity were risk factors for metformin gastrointestinal intolerance. Conclusion: Our study found that the Met420del variant of SLC22A1 (rs72552763) was not associated with metformin induced gastrointestinal intolerance in Ethiopian patients with T2DM. This is the study first to investigate the association of rs72552763 with metformin intolerance in the Ethiopian population with T2DM. However, the findings need to be cautiously interpreted given the relatively small sample size. In addition, a more complete investigation of SLC22A1 variants would be required to fully assess the effect of the gene on metformin induced gastrointestinal intolerance as several variants with a more severe loss of function have been described.

Association of Met420del Variant of Metformin Transporter Gene SLC22A1 with Metformin Treatment Response in Ethiopian Patients with Type 2 Diabetes.

Objective: This study aimed to evaluate whether the M420del variants of SLC22A1 (rs72552763) is associated with metformin treatment response in Ethiopian patients with type 2 diabetes mellitus (T2DM). Patients and Methods: A prospective observational cohort study was conducted on 86 patients with T2DM who had been receiving metformin monotherapy for <1 year. Patients showing ≥0.5% reduction in HbA1c levels from baseline within 3 months and remained low for at least another 3 months were defined as responders while those patients with <0.5% reduction in HbA1c levels and/or those whom started a new class of glucose-lowering drug(s) because of unsatisfactory reduction were defined as non-responders. In addition, good glycemic control was observed when HbA1c ≤7.0%, and the above values were regarded as poor. Genotyping of rs72552763 SNP was performed using TaqMan® Drug Metabolism Enzyme Genotyping Assay and its association with metformin response and glycemic control were assessed by measuring the change in HbA1c and fasting blood glucose levels using Chi-square, logistic regression and Mann-Whitney U-test. Statistical significance was set at p <0.05. Results: The minor allele frequency of the rs72552763 SNP of SLC22A1 was 9.3%. Metformin response was significantly higher in deletion_GAT (del_G) genotypes as compared to the wild-type GAT_GAT (G_G) genotypes. Furthermore, a significantly lower median treatment HbA1 level was found in del_G genotypes as compared to G_G genotypes. However, the association of rs72552763 with metformin response was not replicated at the allele level. In contrast, the minor del_allele was significantly associated with good glycemic control compared to the G_allele, though not replicated at del_G genotypes level. Conclusion: This study demonstrated that metformin response was significantly higher in study participants with a heterozygous carrier of M420del variants of SLC22A1 as compared to the wild-type G_G genotypes after 3 months of treatment.

Tuberculosis and isoniazid prophylaxis among adult HIV positive patients on ART in Northwest Ethiopia.

BACKGROUND: Although antiretroviral therapy (ART) can avert tuberculosis (TB) incidence among human immunodeficiency virus (HIV) infected patients, the concomitant use of ART with isoniazid (INH) has a paramount effect. Despite this evidence, there is a paucity of data regarding TB incidence among HIV patients on ART with and without isoniazid prophylaxis and its predictors. Thus, this study sought to assess the incidence and predictors of TB among adult HIV positive patients on ART. METHODS: This was a hospital based retrospective study including 368 adult HIV positive patients on ART in Gondar comprehensive specialized hospital between January 1, 2016, and April 30, 2019. Data was extracted from clinical laboratory and HIV care ART follow up clinic. The bi-variable and multivariable regression models were used to ascertain predictors of incident TB. Data was analyzed using SPSS version 20 software. RESULTS: A total of 335 adult HIV positive patients were included in the analysis, of whom, 56 (16.7%) were developed incident TB. Being ambulatory and bedridden (AOR: 2.2, 95% CI: 1.1, 4.6), advanced WHO clinical HIV disease stage (III and IV) (AOR: 3.2, 95% CI: 1.6, 6.1), not taking INH (AOR: 2.8, 95% CI: 1.3, 5.9), and baseline CD4+ T cell count ≤ 200 cell/mm3 (AOR: 3.6, 95% CI: 1.8, 7.2) were found to be the predictors of tuberculosis incidence. CONCLUSION: The study indicated a high TB incidence among HIV positive patients in Gondar. Therefore, scaling up the isoniazid preventive therapy program and its strict compliance is necessary to avert HIV fueled tuberculosis in HIV endemic areas.

Saliva is superior over nasopharyngeal swab for detecting SARS-CoV2 in COVID-19 patients.

Scaling up of diagnostic capacity is needed to mitigate the global pandemic of SARS-CoV2. However, there are challenges including shortage of sample collection swabs and transport medium. Saliva has been recommended as a simple, low-cost, non-invasive option. However, data from different populations and settings are limited. Here, we showed that saliva could be a good alternative sample to diagnose COVID-19 patients. Pair of NPS-saliva samples was collected from 152 symptomatic; confirmed COVID-19 patients, and compared their positivity rate, viral load, and duration of viral shedding. From 152 patients, 80 (52.63%) tested positive and 72 (47.37%) were negative for SARSA-CoV2 in NPS sample. In saliva, 129 (92.14%) were tested positive and 11 (7.86%) were negative on the day of admission to hospital. The overall percent agreement of RT-PCR result of Saliva to NPS was 70% (196/280). A comparison of viral load from 72 NPS-saliva pair samples on day of admission shows saliva contains significantly higher viral load (P < 0.001). In conclusion, saliva has higher yield in detecting SARS-CoV2, and COVID-19 patients show higher viral load and prolonged period of viral shedding in saliva. Therefore, we recommend saliva as a better alternative sample to NPS to diagnose COVID-19 patients.

Bacterial profile of high-touch surfaces, leftover drugs and antiseptics together with their antimicrobial susceptibility patterns at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.

BACKGROUND: The hospital environment serves as a source of nosocomial infections, which pose a major therapeutic challenge. Although many bacteria species are common in hospital environments, their distribution, frequency, and antimicrobial susceptibility pattern from high-touch surfaces, leftover drugs, and antiseptics in different wards remain largely unknown. Hence, the aim of this study was to assess the magnitude and frequency of bacterial contaminants and their antimicrobial susceptibility patterns. METHODS: A total of 384 samples were collected from five selected wards and processed according to standard bacteriological procedures. Samples were collected from high-touch surface using swabs and inoculated on Blood agar, MacConkey agar, Chocolate agar and Mannitol salt agar plates, and incubated at 37 °C for 24 h. On the other hand, the leftover drugs and 80% ethanol samples were collected using sterile cotton swab immersed in sterile tryptone soy broth then inoculated on culture medias and incubated at 37 °C for 24 h. Identification of bacteria species was done using the morphological characteristics, Gram stain, and biochemical tests while antimicrobial susceptibility tests were done using modified Kirby-Bauer disk diffusion technique following the Clinical Laboratory Standards Institute 2021guidelines. RESULTS: Among the 384 samples processed, 102 (26.6%) were culture positive and a total of 114 bacterial isolates were identified. Gram-positive bacterial isolates were predominant, 64.9%, while Gram-negatives were 35.1%. The most frequently isolated bacteria were coagulase negative Staphylococci (38.6%) followed by S. aureus (13.2%) and P. aeruginosa (11.4%). On the other hand, the proportion of bacteria isolated from surgical ward, post-natal ward, orthopedic ward, trauma ward, and neonatal intensive care unit ward were 24.6, 21, 20.2, 18.4,15.8%, respectively. Sinks were mainly contaminated with Klebsiella species (81.8%) and A. baumannii (55.6%), while A. baumannii (22.2%) was the most contaminant for 80% ethanol. Gram-positive bacteria had significantly high resistance levels to penicillin (67.6%), cotrimoxazole (67.8%), and cefepime (80%). On the other hand, Gram-negative bacteria revealed the highest resistance levels to tetracycline (82.4%), amoxicillin-clavulanic acid (76.5%), cefepime (66.7%), ceftazidime (67.5%), and piperacillin (92.3%). Moreover, the proportion of multidrug resistant bacteria isolates was 44.7%. CONCLUSIONS: Data of the present study showed that coagulase negative Staphylococci was the dominant bacterial isolates followed by S. aureus and P. aeruginosa. The proportion of multi-drug resistant bacteria isolates was relatively high. Therefore, appropriate infection prevention and control measures should be implemented.

Bacterial Bloodstream Infections and their Antimicrobial Susceptibility Patterns in Children and Adults in Ethiopia: a 6-Year Retrospective Study.

BACKGROUND: In sub-Saharan Africa, bacterial bloodstream infection is the most common cause of morbidity and mortality. Regular antimicrobial surveillance is required to understand resistance development and to inform clinicians and policymakers on best empiric antibiotic choice, such type of data are scarce in the study area. This study aimed to determine bacterial profiles and their antibiotic susceptibility patterns from patients with suspected septicemia at the University of Gondar comprehensive specialized hospital, northwest Ethiopia, over a six-year period. METHODS: We carried out a six-year (January 2, 2012, to January 1, 2018) retrospective analysis of blood cultures from patients with suspected septicemia. Laboratory report data were used to determine patient demographic, bacterial profiles, and antimicrobial resistance patterns. A total of 2,404 blood cultures were processed during the study period. Data were analyzed using SPSS version 20 software and the results were summarized using tables and graphs. RESULTS: Of the 2,404 blood cultures, 489 (20.7%, [95% CI, 19.2 - 22.3%]) bacteria isolates were obtained. The most common isolates were Staphylococcus aureus (215; 43.2%), followed by Klebsiella spp (67; 13.5%), coagulase-negative staphylococcus (62; 12.4%), Escherichia coli (38; 7.6%), viridans streptococci (25; 5%), Citrobacter spp (17; 3.4%), Enterobacter spp (15; 3%), and Streptococcus pneumoniae (12; 2.4%). Methicillin-resistant S. aureus isolation rate was 21/44 (47.7%). Gram-positive and negative bacteria showed high resistance to older antimicrobials, namely ampicillin, erythromycin, tetracycline, gentamicin, and trimethoprim-sulphamethoxazole. Gram-negative bacteria had a high level of resistance to 3rd generation cephalosporins, but both Gram-positive and negative bacteria were susceptible to ciprofloxacin. CONCLUSIONS: S. aureus, CoNS, S. pneumoniae, Klebsiella spp and E. coli remain the most important bacteria responsible for bloodstream infection in this study. Those pathogens showed a high rate of resistance to old antibiotics. Among the tested antimicrobials, ciprofloxacin was found to be the most effective drug to inhibit the in-vitro growth of both Gram-positive and negative bacteria. Therefore, there is a need for continuous screening of AMR from blood cultures to control the spread of drug resistant isolates in the study area.

Seroepidemiology and model-based prediction of SARS-CoV-2 in Ethiopia: longitudinal cohort study among front-line hospital workers and communities.

BACKGROUND: Over 1 year since the first reported case, the true COVID-19 burden in Ethiopia remains unknown due to insufficient surveillance. We aimed to investigate the seroepidemiology of SARS-CoV-2 among front-line hospital workers and communities in Ethiopia. METHODS: We did a population-based, longitudinal cohort study at two tertiary teaching hospitals involving hospital workers, rural residents, and urban communities in Jimma and Addis Ababa. Hospital workers were recruited at both hospitals, and community participants were recruited by convenience sampling including urban metropolitan settings, urban and semi-urban settings, and rural communities. Participants were eligible if they were aged 18 years or older, had provided written informed consent, and were willing to provide blood samples by venepuncture. Only one participant per household was recruited. Serology was done with Elecsys anti-SARS-CoV-2 anti-nucleocapsid assay in three consecutive rounds, with a mean interval of 6 weeks between tests, to obtain seroprevalence and incidence estimates within the cohorts. FINDINGS: Between Aug 5, 2020, and April 10, 2021, we did three survey rounds with a total of 1104 hospital workers and 1229 community residents participating. SARS-CoV-2 seroprevalence among hospital workers increased strongly during the study period: in Addis Ababa, it increased from 10·9% (95% credible interval [CrI] 8·3-13·8) in August, 2020, to 53·7% (44·8-62·5) in February, 2021, with an incidence rate of 2223 per 100 000 person-weeks (95% CI 1785-2696); in Jimma Town, it increased from 30·8% (95% CrI 26·9-34·8) in November, 2020, to 56·1% (51·1-61·1) in February, 2021, with an incidence rate of 3810 per 100 000 person-weeks (95% CI 3149-4540). Among urban communities, an almost 40% increase in seroprevalence was observed in early 2021, with incidence rates of 1622 per 100 000 person-weeks (1004-2429) in Jimma Town and 4646 per 100 000 person-weeks (2797-7255) in Addis Ababa. Seroprevalence in rural communities increased from 18·0% (95% CrI 13·5-23·2) in November, 2020, to 31·0% (22·3-40·3) in March, 2021. INTERPRETATION: SARS-CoV-2 spread in Ethiopia has been highly dynamic among hospital worker and urban communities. We can speculate that the greatest wave of SARS-CoV-2 infections is currently evolving in rural Ethiopia, and thus requires focused attention regarding health-care burden and disease prevention. FUNDING: Bavarian State Ministry of Sciences, Research, and the Arts; Germany Ministry of Education and Research; EU Horizon 2020 programme; Deutsche Forschungsgemeinschaft; and Volkswagenstiftung.

Knowledge, attitude and practices on cervical cancer screening among undergraduate female students in University of Gondar, Northwest Ethiopia: an institution based cross sectional study.

BACKGROUND: Cervical cancer is a major public health problem. In the world, cervical cancer is the fourth most common cancer among women and it is one of the leading causes of cancer mortality in females. It is the second most common women cancer in Ethiopia with almost 6300 new cases and 4884 deaths annually. Despite the high burden of new cases and deaths, there is a scarcity of data on knowledge, attitude and practices (KAP) towards cervical cancer screening among female university students in Ethiopia particularly in the study area. Therefore, the present study was aimed to assess the KAP of undergraduate female students towards cervical cancer screening. METHODS: An institution based cross-sectional study was conducted in April 2018 at the University of Gondar, College of Medicine and Health Sciences undergraduate female students. Pretested, self-administered questionnaire was used for data collection. Four hundred and three female students were recruited by a simple random sampling method and the data were entered and analyzed using SPSS version 20 statistical packages. Descriptive data analysis was used to report the results. RESULTS: More than half of the respondents (59.3.3%) had good knowledge, whereas nearly 67.7% of the respondents had favorable attitude towards cervical cancer. However, less than 1% of the respondents had been screened for cervical cancer. CONCLUSION: Although undergraduate female students had apparently good knowledge and favorable attitude, their practices on cervical cancer screening were quite low. Therefore, the health sectors and the gender streaming office of the university mobilize students to strengthen the uptake the cervical cancer screening practice.

Antibiotic Susceptibility Pattern and Associated Factors of Methicillin-Resistant Staphylococcus aureus among Dermatological Patients at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia: a Prospective Cross-Sectional Study.

BACKGROUND: Determination of the distribution pattern and associated factors of skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA) is a fundamental step to set up an effective control program to improve the health status. The purpose of this study was to assess the antibiotic susceptibility pattern and associated factors of MRSA among dermatological patients. METHODS: In this hospital-based, prospective, cross-sectional study, 189 pus and skin swabs were collected from dermatological patients through a convenient sampling method in 2019. A structured questionnaire was employed for data collection of associated factors. Pus and skin swabs were collected using a sterile cotton swab and needle aspiration, then inoculated on mannitol salt agar. We followed a standard bacteriological procedure for identification of MRSA. Logistic regression models at a 95% confidence interval and p-value < 0.05 was considered for significance. RESULTS: A total of 127/189 (67.2%) of Staphylococcus aureus isolates were recovered and 80/127 (63.0%) were MRSA. Over 97% of Staphylococcus aureus isolates showed resistance to penicillin. MRSA was sensitive to gentamicin (78.75%), ciprofloxacin (83.75%), and clindamycin (86.25%). Frequency of washing body, method of hand washing, and recent hospitalization had a significant association with MRSA skin infection. CONCLUSIONS: The study revealed a high prevalence of MRSA among dermatological patients. Staphylococcus aureus showed a very high degree of resistance to different antimicrobials and most of Staphylococcus aureus isolates also showed multidrug-resistance patterns.

Assessment of the effect of antiretroviral therapy on renal and liver functions among HIV-infected patients: a retrospective study.

BACKGROUND: The emergence of highly active antiretroviral therapy (HAART) has dramatically improved quality of life in prolonging survival of human immunodeficiency virus (HIV)-infected patients on treatment in developed as well as developing countries. However, the main shortcoming of HAART in long-term use is its potential to cause liver and kidney derangements that may be life threatening. The drugs are actively accumulated in the proximal renal tubule resulting in functional disturbance with mitochondrial injury being one of the most important targets recognized. Therefore, the aim of this study was to assess the adverse effects of HAART on kidney and liver functions among HIV-infected patients presenting to the University of Gondar Hospital, Ethiopia. MATERIALS AND METHODS: An institution-based retrospective study was conducted from 2010 to 2015 on a subset of HIV-infected patients. Data were collected from the registration book of the University of Gondar Hospital antiretroviral clinic laboratory after checking the completeness of age, gender, creatinine, blood urea nitrogen, and alanine aminotransferase level. Data were entered and analyzed using SPSS version 20. Descriptive statistics, chi-square test, one-way analysis of variance, and logistic regression were done to determine associations. A P-value <0.05 was considered statistically significant. RESULTS: A total of 275 study subjects were included in the study. Of these, 62.2% were females, and the overall prevalence of chronic kidney disease (CKD) before and after treatment was 3.6% and 11.7%, respectively. A majority of the CKD patients were in stage 3 for patients after treatment. The overall prevalence of hepatotoxicity was 6.5% and 16.7% before and after treatment, respectively. A majority of the patients developed Grade 2 hepatotoxicity 66.7% and 65.2% before and after treatment, respectively. Binary and multiple logistic regression analysis indicated that the female gender was a risk factor for CKD. CONCLUSION: The prevalence of nephrotoxicity and hepatotoxicity were high among patients who took HAART. Stage 3 nephrotoxicity and Grade 2 hepatotoxicity had the highest incidences of the total toxicities, and the female gender was a risk factor for nephrotoxicity. Further prospective studies are recommended to determine the effect of HAART and contributing factors.

Vitamin A deficiency during pregnancy of HIV infected and non-infected women in tropical settings of Northwest Ethiopia.

BACKGROUND: Vitamin A deficiency (VAD) is known to be a major public health problem among women of reproductive age in South East Asia and Africa. In Ethiopia, there are no studies conducted on serum vitamin A status of HIV-infected pregnant women. Therefore, the present study was aimed at determining the level of serum vitamin A and VAD among pregnant women with and without HIV infection in tropical settings of Northwest Ethiopia. METHODS: In this cross-sectional study, blood samples were collected from 423 pregnant women and from 55 healthy volunteers who visited the University of Gondar Hospital. Serum concentration of vitamin A was measured by high performance liquid chromatography. RESULTS: After controlling for total serum protein, albumin and demographic variables, the mean ± SD serum vitamin A in HIV seropositive pregnant women (0.96 ± 0.42 µmol/L) was significantly lower than that in pregnant women without HIV infection (1.10 ± 0.45 µmol/L, P < 0.05). Likewise, the level of serum vitamin A in HIV seropositive non-pregnant women (0.74 ± 0.39) was significantly lower than that in HIV negative non-pregnant women (1.18 ± 0.59 µmol/L, P < 0.004). VAD (serum retinol < 0.7 µmol/L) was observed in 18.4% and 17.7% of HIV infected and uninfected pregnant women, respectively. Forty six percent of non-pregnant women with HIV infection had VAD while only 28% controls were deficient for vitamin A (P = 0.002). CONCLUSION: The present study shows that VAD is a major public health problem among pregnant women in the tropical settings of Northwest Ethiopia. Considering the possible implications of VAD during pregnancy, we recommend multivitamin (which has a lower level of vitamin A) supplementation in the care and management of pregnant women with or without HIV infection.