The Coronavirus disease-19 (COVID-19) pandemic is still devastating the world causing significant social, economic, and political chaos. Corresponding to the absence of globally approved antiviral drugs for treatment and vaccines for controlling the pandemic, the number of cases and/or mortalities are still rising. Current patient management relies on supportive treatment and the use of repurposed drugs as an indispensable option. Of a crucial role in the viral life cycle, ongoing studies are looking for potential inhibitors to the main protease (Mpro) of severe acute respiratory syndrome Coronavirus -2 (SARS-CoV-2) to tackle the pandemic. Although promising results have been achieved in searching for drugs inhibiting the Mpro, work remains to be done on designing structure-based improved drugs. This review discusses the structural basis of potential inhibitors targeting SARS-CoV-2 Mpro, identifies gaps, and provides future directions. Further, compounds with potential Mpro based antiviral activity are highlighted.

BackgroundStaphylococcus aureus particularly MRSA strains are one of the major causes of community and hospital acquired bacterial infections. They are also becoming increasingly multi-drug resistant and have recently developed resistance to vancomycin, which has been used successfully to treat MRSA for many years. In-vitro determination of drug resistance patterns of S. aureus is critical for the selection of effective drugs for the treatment of staphylococci infections.The main aim of this study was to determine the prevalence of methicillin resistant S. aureus strains from different clinical specimens from patients referred for routine culture and sensitivity testing.MethodA cross sectional study was conducted among 1360 participants at Yekatit 12 Hospital Medical College in Ethiopia from September 2013 to April 2014. Clinical samples from various anatomical sites of study participants were cultured on blood agar and mannitol salt agar and identified to be S. aureus by using catalase, coagulase and DNAse tests. S. aureus isolates then were screened for MRSA using 30 μg cefoxitin disc and other 11 antimicrobial drugs by disc diffusion procedure, and agar dilution and E tests for vancomycin. All S. aureus isolates examined for beta-lactamase production by employing nitrocefin. Data were analyzed using SPSS version 20 software and logistic regressions were applied to assess any association between dependent and independent variables.ResultsOf 1360 clinical specimens analyzed S. aureus was recovered from (194, 14.3 %). Rate of isolation of S. aureus with regard to clinical specimens was the highest in pus (118, 55.4 %).No S. aureus was isolated from CSF and urethral discharge. Out of 194 S. aureus isolates, (34, 17.5 %) were found out to be MRSA and the remaining (160, 82.5 %) were MSSA. Ninety eight (50.5 %) S. aureus were multi drug resistant and the highest isolates were resistant to penicillin (187, 96.4 %) and least resistant for clindamycin (23, 11.9 %) and vancomycin (10, 5.1 %). MRSA strains were 100 % resistant to penicillin G, erythromycin, trimethoprim-sulfamethoxazole and least resistant to vancomycin (10, 29.4 %). Out of 194 S. aureus isolates (153, 79.0 %) were beta-lactamase producers.ConclusionIn this study S. aureus isolates exhibited very high degree of resistance to different antibiotics. The isolates were also multidrug resistant to several combinations of the tested antibiotics. The emergence of vancomycin resistant S. aureus highlights the value of prudent prescribing of antibiotics and avoiding their irrational use.

Background Intestinal parasitosis is a common disease that causes misery and disability in poor populations. The number of individuals affected is staggering. From two billion peoples who harbor parasites worldwide, 300 million suffer severe morbidity and more than 25% of pregnant women are infected with hookworm, which causes intestinal bleeding and blood loss, and has been most commonly associated with anemia. Intestinal parasite infection during pregnancy has been associated with iron deficiency, maternal anemia, and impaired nutritional status, as well as decreased infant birth weight. Objective This study aimed to assess the effects of intestinal parasite infection on hematological profiles of pregnant women attending antenatal care in Debre Markos Referral Hospital from December 2017 to February 2019. Method A prospective cohort study design was conducted among 94 intestinal parasite-infected pregnant women as an exposed group and 187 pregnant women free from intestinal parasite were used as a control group. The effect of intestinal parasites on hematological profiles of pregnant women was assessed at Debre Markos Referral Hospital antenatal care ward. Socio-demographic data and nutrition status were assessed by using structured questionnaires and mid-upper arm circumference (MUAC), respectively. Two ml of venous blood and 2 gm of stool samples were collected to analyze the hematological profiles and detect intestinal parasites, respectively. Wet mount and formol-ether concentration (FEC) techniques were used to detect intestinal parasites. Hematological profile was analyzed using Mind ray BC-3000 plus instrument. Data were double entered into EpiData version 3.1 software and exported to SPSS version 24 software for analysis. Results were presented using tables and graphs. Associations of hemoglobin levels with intestinal parasitic infections were determined using binary logistic regression models. P≤0.05 was considered statistically significant. The mean hematological profile difference between parasite-infected and parasite-free pregnant women was computed using independent t-test. Results In the present study, the predominant parasites identified were Entamoeba histolytica, hookworm, Giardia lamblia, Schistosoma mansoni, and Ascaris lumbricoides. About 8.2% of intestinal parasite-infected pregnant women had mild anemia while 4% had moderate anemia. Only 1.2% of intestinal parasite-free pregnant women developed moderate anemia. The mean HGB, HCT, MCV, MCH, and MCHC values of intestinal parasite-infected pregnant women were 12.8g/dl, 38.2%, 94.7fl, 33.1pg and 34.7g/dl, respectively. But the mean HGB, HCT, MCV, MCH and MCHC values of pregnant women who were free from intestinal parasites were 14.4 g/dl, 39.8%, 94.9fl, 33.9pg and 35.5g/dl, respectively. Anemia was strongly associated with hookworm (AOR = 21.29, 95%CI: 8.28–54.75, P<0.001), S.mansoni (AOR = 63.73, 95% CI: 19.15–212, P<0.001) and A.lumbricoide (AOR = 14.12, 95% CI 3.28–60.65, P<0.001). Conclusion Intestinal parasitic infection in pregnant women caused adverse impact on hematological profiles and was an independent predictor of anemia. Intestinal parasitic infection significantly decreased pregnant the level of HGB, HCT, MCV, MCH, and MCHC values. To minimize maternal anemia deworming could be good before pregnancy.

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.

Background External eye infection caused by bacteria can lead to reduced vision and blindness. Therefore, pathogen isolation and antimicrobial susceptibility testing are vital for the prevention and control of ocular diseases. Objective The main aim of this study was to assess bacterial isolates, their antimicrobial susceptibility pattern, and associated factors of external ocular infection (EOI) among patients attended eye clinic at Debre Markos Comprehensive Specialized Hospital (DMCSH), Northwest Ethiopia. Methods We conducted a cross-sectional study in patients with external ocular infections from January 1, 2021, to June 30, 2021, at DMCSH. Socio-demographic and clinical data were collected using semi-structured questionnaires. Following standard protocols, external ocular swabs were collected and inoculated onto blood agar, chocolate agar, MacConkey agar and mannitol salt agar (MSA). Finally, bacterial isolates were identified by Gram stain, colony morphology, and biochemical tests. Antimicrobial susceptibility testing was done by using the modified Kirby-Bauer disk diffusion technique according to Clinical and Laboratory Standards Institute (CLSI) guideline. Cleaned and coded data were entered into EpiData version 4.2 software and exported to Statistical Packages for Social Sciences (SPSS) version 22 for analysis. Bivariate logistic regression was applied to investigate the association between predictors and outcome variables. P-values ≤ 0.05 with 95% confidence interval were considered statistically significant. Results Two hundred seven study participants were enrolled in this study. More than half of them (57.5%, 119/207) were males, and 37.7% (78/207) of them were ≥ 65 years old. A total of 130 (62.8%) bacterial isolates were identified, with Gram-positive bacteria accounting for 78.5% (102/130) of the isolates. Staphylococcus aureus was the most common isolate with a 46.2% (60/130) prevalence. Ciprofloxacin was comparatively effective against Gram-positive and Gram-negative bacteria. The prevalence of culture-confirmed bacteria was significantly associated with age groups 15–24 (AOR: 9.18, 95%CI: 1.01–82.80; P = 0.049) and 25–64 (AOR: 7.47, 95%CI: 1.06–52.31; P = 0.043). Being farmer (AOR: 5.33, 95% CI: 1.04–37.33; P = 0.045), previous history of eye surgery (AOR: 5.39, 95% CI: 1.66–17.48; P = 0.005), less frequency of face washing (AOR: 5.32, 95% CI: 1.31–7.23; P = 0.010) and face washing once a day (AOR: 3.07, 95% CI: 1.13–25.13; P = 0.035) were also significantly associated with the prevalence of culture-confirmed bacteria. Conclusion The prevalence of culture-confirmed bacteria among patients with EOI was high in the study area. A considerable proportion of bacterial isolates exhibited mono and/or multi-drug resistance. Age (15–64 years), being farmer, previous history of eye surgery and less frequency of face washing were significantly associated with the prevalence of culture-confirmed bacteria. Bacterial isolation and antibiotic susceptibility testing should be routinely performed in the study area to combat the emergence of antibiotic resistance.

Background Intestinal parasitic infection has serious medical and public health impacts in developing countries. Intestinal parasites were under reported via direct wet mount method due to its poor sensitivity. So, the selection of a more sensitive and reliable diagnostic method is essential. Objective The aim of the study was to evaluate the diagnostic performance of wet mount and concentration techniques of stool examination for intestinal parasites identification. Methods A cross-sectional study among 797 pregnant women was conducted from October 2018 to February 2019 at Debre Markos Comprehensive Specialized Hospital. The study participants were selected by using a systematic random sampling technique. Stool sample was processed by using Wet Mount (WM) and Formol-Ether Concentration (FEC) techniques. Data was entered into Epi-data version 3.1 and analysis using SPSS version 20.0. The sensitivity, specificity, positive predictive value, and negative predictive value were determined against the combined result as “Gold” standard. Kappa value was determined to estimate the agreement of the diagnostic methods. Results The overall prevalence of intestinal parasites (IP) was 35.2% with a combined method. By using WM and FEC the prevalence of IP was 13.1% and 25.7%, respectively. The sensitivity and negative predictive value of WM method were 37.1% and 74.6%, and for FEC method 73.5% and 87.5%, respectively. Test efficiency of direct WM and FEC were 77.9% and 90.7%, respectively. The agreement of WM and FEC techniques with combined technique were moderate (κ=0.434) and perfect (κ=0.783), respectively. Conclusion The prevalence of intestinal parasites was under-reported by wet mount technique. The diagnostic performance of FEC technique for the diagnosis of intestinal parasites in pregnant women was notably high as compared to WM technique in the present study. Therefore, the WM and FEC combined method should be used as a routine diagnostic technique for the diagnosis of intestinal parasites identification.

Background Hepatitis B virus is a public health problem in the world. It is a major cause of chronic hepatitis, cirrhosis, and hepatic cellular carcinoma. The presence of a confirmed HBsAg result is indicative of ongoing HBV infection. This study aims to assess the sero-prevalence and associated factors of the hepatitis B virus among pregnant women in North West Ethiopia. Methods and Materials An institution-based cross-sectional study was conducted at Debre Markos Referral Hospital from January to July 2017. A consecutive 338 pregnant women attending the antenatal clinic were included. A structured questionnaire was used to assess hepatitis B virus infection associated factors and some socio-demographic characteristics. A 5 mL of venous blood was collected from each study participant and plasma was separated and analyzed using a rapid HBsAg kit and further confirmed by double sandwich ELISA. The data were analyzed using SPSS software version 24. Results The mean age of the study participants was 27 (SD ± 4.75) years. The sero-prevalence of hepatitis B virus in pregnant women was 28 (8.3%). Body tattooing practice (AOR = 4.94 95% CI, 1.87–13.0), multi-partner sexual intercourse (AOR = 4.48 95% CI, 1.89–10.5) and family hepatitis B history (AOR = 7.40 95% CI, 2.23–24.5) were statistically significantly associated with HBV infection (p = 0.001). Conclusion The prevalence of hepatitis B infection is very high among pregnant women in the study area. Awareness creation on modes of transmission and early screening of all pregnant women attending antenatal care must be strengthened to minimize and control infection.

Background: Staphylococcus aureus particularly methicilin resistant S. aureus strains are one of the major causes of community and hospital acquired bacterial infections, often causing postoperative and burn wound infections. In-vitro determination of drug resistance patterns of S. aureus is critical for the selection of effective drugs for the treatment of staphylococci infections. Objective: The aim of this study was to determine methicillin and antimicrobial susceptibility pattern of S. aureus from postoperative and burn wound patients in Ethiopia. Materials and Methods: A cross sectional study was conducted among 378 patients at Yekatit 12 Hospital Medical College from September 2013 to August 2014 in Ethiopia. Swabs from postoperative and burn wound were collected. Swabs were cultured on blood agar and mannitol salt agar and incubated at 35-37°C aerobically for 18-24 hours. Cultures with typical characteristics were identified to S. aureus by DNAse agar test. S. aureus were then screened for MRSA using 30µg cefoxitin disc. The drug susceptibility patterns of S. aureus to eleven drugs were determined by disc diffusion procedure and agar dilution for vancomycin. All S. aureus isolates examined for beta-lactamase production by employing nitrocefin. Data were analyzed using SPSS version 20 software and logistic regressions were applied to assess any association between dependent and independent variables. P values < 0.05 were taken as statistically significant. Results: Of the 378 swabs analyzed, S. aureus was recovered from 179 (47.4%). The prevalence of S. aurues was higher in females than males 95(53%) versus 84(47%). Out of 179 S. aureus isolates, 67(37.43%) were found out to be MRSA and the remaining 112(62.57%) were MSSA. S. aureus isolates were more resistant to penicillin 172(96.1%) and least resistant for vancomycin 10(5.6%) and cephalothin 9(5.0%). MRSA isolates were 67(100%) resistant for penicillin, 63(94.0%) for erythromycin, 62(92.5%) for trimethoprim-sulfamethoxazole and least resistant for cephalothin 9(13.4%) and vancomycin 10(15.0%). Among 179 S. aureus isolates, 145(81.0%) were beta-lactamase producers. Furthermore, of 67 MRSA isolates, 61(91.0%) and out of 112 MSSA strains 99(88.4%) were beta-lactamase producers. Conclusion: In this study S. aureus isolates exhibited very high degree of resistance to different antibiotics. The prevalence of MRSA was high and this should necessitate caution in prescription of antibiotics without proper indication. The isolates were also multidrug resistant to several combinations of the tested antibiotics. The emergence of vancomycin resistant S. aureus highlights the value of prudent prescribing of antibiotics and avoiding their irrational use.