Yibeltal Akelew

Background Antibiotic resistance (AMR) remains a global public health threat with a high burden in sub-Saharan countries. The overuse of antimicrobials in the clinical setting is the main factor for the spread of antibiotic resistance. Diagnostic uncertainty in differentiating between bacterial and viral infections is the major contributor to antimicrobial overuse. The available biomarkers lack specificity in guiding clinicians to make antibiotic decisions and only estimate bacterial infection. Main body Myxovirus resistance (Mx) proteins are a type of interferon (IFN)-inducible protein that belongs to the dynamin superfamily of large guanine triphosphates (GTPases) involved in broad antiviral responses. Myxovirus resistance protein A (MxA) is a host-derived biomarker with antiviral properties against various viruses. It is induced by IFN I and IFN III as part of the innate immune response. Its basal level is < 15 ng/ml and elevated levels are detectable 1-2 h after IFN induction and remain detectable in serum up to 10 days after viral infection. Increased levels in the blood are associated with viral infection and remain low during bacterial infections. This biomarker showed promising performance in diagnosing undifferentiated febrile patients with respiratory tract infections. In this review, we discuss the role of Mx proteins, specifically MxA, in diagnosing acute viral infections, including how they are induced and their potential as diagnostic tools. Methods A comprehensive electronic search was conducted in Scopus and Medline (using the PubMed interface) regarding myxovirus resistance protein A as a biomarker for acute viral infection. In the search strategy, English language was used without date restriction. Manual search was also performed when appropriate. Conclusions Elevated MxA combined with other biomarkers, such as CRP and PCT, is a promising tool for identifying patients with viral infections. Therefore, incorporating MxA in the existing point of care formats help to improve the antibiotic stewardship programs and future randomized controlled trials are recommended to evaluate its utility in medical practice.

Extracellular vesicles (EV) can be produced as part of pathology and physiology with increased amounts in pathological conditions. EVs can carry and transfer cargo such as proteins, nucleic acids, and lipids to target cells and mediate intercellular communication resulting in modulation of gene expression, signaling pathways, and phenotype of recipient cells. EVs greatly influence the extracellular environment and the immune response. Their immunomodulatory properties are crucial in rheumatoid arthritis (RA), a condition marked by dysregulated immune response. EVs can modulate the functions of innate and adaptive immune cells in RA pathogenesis. Differentially expressed EV-associated molecules in RA, such as microRNAs (miRNAs), long-noncoding RNAs (lncRNAs), messenger RNAs (mRNAs) and proteins are promising markers to diagnose the disease. miRNA, lncRNA, and circular RNA (circRNA) cargos in EV regulate inflammation and the pathogenic functions of RA fibroblast-like synoviocytes (RA-FLS). Downregulated molecules in RA tissue and drugs can be encapsulated in EVs for RA therapy. This review provides an updated overview of EVs’ immunomodulatory, diagnostic, and therapeutic roles, particularly emphasizing mesenchymal stem cell-derived EVs (MSC-EVs).

Acute myeloid leukemia (AML) is the abnormal proliferation of immature myeloid blast cells in the bone marrow. Currently, there are no universally recognized biomarkers for the early diagnosis, prognosis and effective treatment of AML to improve the overall survival of patients. Recent studies, however, have demonstrated that long noncoding RNAs (lncRNAs) are promising targets for the early diagnosis, prognosis and treatment of AML. A critical review of available data would be important to identify study gaps and provide perspectives. In this review, we explored comprehensive information on the potential use of lncRNAs as targets for the diagnosis, prognosis, and treatment of AML. LncRNAs are nonprotein-coding RNAs that are approximately 200 nucleotides long and play important roles in the regulation, metabolism and differentiation of tissues. In addition, they play important roles in the diagnosis, prognosis and treatment of different cancers, including AML. LncRNAs play multifaceted roles as oncogenes or tumor suppressor genes. Recently, deregulated lncRNAs were identified as novel players in the development of AML, making them promising prognostic indicators. Given that lncRNAs could have potential diagnostic marker roles, the lack of sufficient evidence identifying specific lncRNAs expressed in specific cancers hampers the use of lncRNAs as diagnostic markers of AML. The complex roles of lncRNAs in the pathophysiology of AML require further scrutiny to identify specific lncRNAs. This review, despite the lack of sufficient literature, discusses the therapeutic, diagnostic and prognostic roles of lncRNAs in AML and provides future insights that will contribute to studies targeting lncRNAs in the diagnosis, treatment, and management of AML.

Human papillomavirus (HPV) therapeutic vaccine development and ongoing clinical trials have revealed viral elimination and the waning of cervical intraepithelial neoplasia (CIN) and cervical cancer. HPV therapeutic vaccines are aimed at treating advanced cancers and pre‑cancerous lesions by generating antibodies and cell‑mediated immunity. The efficacy of a novel high‑risk HPV‑16/18 therapeutic vaccine in treating CIN and cervical cancer was systematically assessed. A total of three databases from 2012 to 2022 were systematically searched. Scopus (https://www.scopus.com/home.uri), PubMed (https://pubmed.ncbi.nlm.nih.gov/), Hinari (https://portal.research4life.org/) and Google Scholar were searched. Original articles conducted in human clinical trials were included based on a predefined inclusion criterion. The Joanna Briggs Institute (JBI) Critical Appraisal tools was utilized for use in the JBI Systematic Reviews Checklist for Systematic Reviews and Research Syntheses (http://joannabriggs.org/research/critical‑appraisal‑tools.html) to assess the risk of bias (RoB). Moreover, five authors worked independently during evidence searching and reached a consensus on all included studies to avoid the RoB. Data were extracted and synthesized from the included studies using an Excel spread sheet. The Preferred Reporting Items for Systematic Reviews and Meta‑Analyses (PRISMA) guidelines were used to select studies and a random model effect was also used to analyze the outcome of the review [I2=0.00%, P=0.93, confidence interval 95%(CI)]. Only eight evidences were included out of 555 studies searched. The efficacy of the novel HR‑HPV 16/18 therapeutic vaccine among 377 women suffering from high‑grade CIN and cervical cancer was 88.33% (333/377). Vaccination was most efficacious (33%, 126/377) and least efficacious (23%, 87/377) in complete lesion regression and partial lesion regression, respectively. However, 12% of the women progressed to cancer. Additionally, 33% (126/377) and 23% (87/377) of women demonstrated complete viral clearance and viral load reduction, respectively. Complete lesion regression and progression of lesion to cancer have the highest and lowest effect sizes: 33% (I²=0.00%, P=0.93, 95% CI=0.60‑60.67), 22% (I²=0.00%, P=0.93, 95% CI=11.40‑55.40), and respectively. The overall effect size of the clinical trial outcome is 27.67% (I²=0.00%, P=0.93, 95% CI=14.30‑41.03). The efficacy of a novel HR‑HPV 16/18 therapeutic vaccine is very promising for high‑grade CIN and cervical cancer therapy. Further studies are urgently required to boost the efficacy of a novel HR‑HPV 16/18 therapeutic vaccine, reduce women's health burden, and improve the quality of human life.

The gut microbiota and short chain fatty acids (SCFA) have been associated with immune regulation and autoimmune diseases. Autoimmune kidney diseases arise from a loss of tolerance to antigens, often with unclear triggers. In this review, we explore the role of the gut microbiome and how disease, diet, and therapy can alter the gut microbiota consortium. Perturbations in the gut microbiota may systemically induce the translocation of microbiota-derived inflammatory molecules such as liposaccharide (LPS) and other toxins by penetrating the gut epithelial barrier. Once in the blood stream, these pro-inflammatory mediators activate immune cells, which release pro-inflammatory molecules, many of which are antigens in autoimmune diseases. The ratio of gut bacteria Bacteroidetes/Firmicutes is associated with worse outcomes in multiple autoimmune kidney diseases including lupus nephritis, MPO-ANCA vasculitis, and Goodpasture’s syndrome. Therapies that enhance SCFA-producing bacteria in the gut have powerful therapeutic potential. Dietary fiber is fermented by gut bacteria which in turn release SCFAs that protect the gut barrier, as well as modulating immune responses towards a tolerogenic anti-inflammatory state. Herein, we describe where the current field of research is and the strategies to harness the gut microbiome as potential therapy.

Autoimmune kidney diseases arise from a loss of tolerance to antigens, often with unclear triggers. In this review we explore the role of the gut microbiome and how disease, diet and therapy can alter the gut microbiota consortium. Perturbations in the gut microbiota may induce the translocation of microbiota-derived inflammatory molecules such as liposaccharide (LPS) and other toxins systemically by penetrating the gut epithelial barrier. Once in the blood stream these pro-inflammatory mediators activate immune cells which release pro-inflammatory molecules many of which are antigens in autoimmune diseases. The ratio of gut bacteria Bacteroidetes:Firmicutes is associated with worse outcomes in multiple autoimmune kidney diseases including Lupus nephritis, MPO-ANCA vasculitis and Goodpasture’s syndrome. Therapies which enhance short chain fatty acid (SCFA)-producing bacteria in the gut have powerful therapeutic potential. Dietary fibre is fermented by gut bacteria which in turn release SCFAs which protect the gut barrier as well as modulate immune responses towards a tolerogenic anti-inflammatory state. Herein, we describe where the current field of research is and the strategies to harness the gut microbiome as potential therapy.

Introduction. Prisoners in Sub-Saharan Africa (SSA) are at a high risk of tuberculosis (TB) infection due to overcrowding and poor ventilation. Consequently, TB is a leading cause of morbidity and mortality in prison, and many inmates face a number of barriers to TB control and had limited information in the region. Thus, the aim of this systematic review and meta-analysis was to estimate the overall pooled prevalence of pulmonary TB and predictors among prison inmates in SSA. Methods. From 2006 to 2019, a systematic review and meta-analysis was conducted using various databases, including PubMed, Embase, Web of Science, and Scopus. The data were extracted in Microsoft Excel using a standardized data extraction format, and the analysis was carried out with STATA version 14. To detect heterogeneity across studies, the and the Cochrane test statistics were computed. To determine the overall prevalence of TB and predictors among prison populations, a random effect meta-analysis model was used. Results. Of the 3,479 retrieved articles, 37studies comprising 72,844 inmates met the inclusion criteria. The pooled prevalence of pulmonary TB among prison inmates in SSA was 7.74% (95% CI: 6.46-8.47). In the subgroup analysis, the highest prevalence was found in the Democratic Republic Congo (DRC) (19.72%) followed by Zambia (11.68%) and then Ethiopia (9.22%). TB/HIV coinfection (OR 4.99 (95% CI: 2.60-9.58)), Body mass index ( ) (OR 3.62 (95% CI: 2.65-6.49)), incarceration (OR 4.52 (95% CI: 2.31-5.68)), and previous TB exposure (OR 2.43 (95% CI: 1.61-3.56)) had higher odds of pulmonary TB among inmates. Conclusion. The prevalence of pulmonary TB among SSA prison inmates was found to be high as compared to total population. TB/HIV coinfection, BMI, incarceration duration, and TB exposure were all predictors with pulmonary tuberculosis in prison inmates. As a result, emphasizing early screening for prisoners at risk of pulmonary TB is an important point to achieving global TB commitments in resource-limited settings.

Introduction: The occurrence of extended spectrum beta lactamase-producing uropathogens, especially in pregnant women can result in life-threatening condition and morbidity for both the mother and the newborn due to very limited drug options for treatment of these pathogens. The aim of this study was to determine the bacterial profile, associated factors, and their antimicrobial susceptibility patterns and to identify extended spectrum beta lactamase-producing bacterial uropathogens. Methods: A hospital-based cross-sectional study was conducted from July to September 2018 on a total of 177 pregnant women with and without symptoms of urinary tract infection at ALERT Hospital, Addis Ababa, Ethiopia. From these study participants, 72 have symptoms, whereas 105 have no symptoms. All urine samples were inoculated onto cysteine lactose electrolyte deficient medium and MacConkey agar. Colonies were counted to check the presence of significant bacteriuria. Pure isolates of bacterial pathogen were characterized and identified at species level by colony morphology, gram stain, and standard biochemical procedures. All Gram-negative isolates were put into Muller–Hinton agar plates for antibiotic susceptibility test by Kirby-Bauer disc diffusion technique. Extended spectrum beta lactamase was detected using double-disk synergy methods on Muller–Hinton agar. The data were double entered into epidemiological Information system and analyzed using Statistical Package for Social Science version 26. Results: The overall proportion of urinary tract infection among pregnant women was 14.7% ( n = 26/177). Klebsiella pneumoniae was the predominant bacterial etiologic agent of urinary tract infection 26.9% ( n = 7/26). The proportion of extended spectrum beta lactamase among Gram-negative isolates was 50% ( n = 6/12). Among extended spectrum beta lactamase-producing isolates (100%), all are resistance to amikacin and gentamicin while intermediate level resistance rate of 66.7% was observed among trimethoprim–sulphamethoxazole. They were susceptible for some limited drugs, and these were Nitrofurantoin (83.3%) and Chloramphenicol (83.3%). Conclusions: Majority of extended spectrum beta lactamase-producing isolates exhibited co-resistance to other commonly prescribed antibiotics. This indicates that the option of treatment for these pathogens rapidly decreased from time to time which results serious life-threatening conditions, especially in mother and newborn unless the appropriate measure is taken.

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is coronavirus isolated from SARS patients. As far as the researchers’ knowledge, there was paucity of studies conducted in Ethiopia, particularly in the study area. As immune protection is arisen from our blood cells, assessing their level will provide a clue for controlling the disease and monitoring the prognosis. This study will also provide additional information for clinical intervention and patient management. Purpose: This study aimed to investigate the hematological profile and clinical outcome of coronavirus disease-19 (COVID-19) among patients admitted to the Debre Markos Isolation and Treatment Center (DMITC). Material and Methods: A prospective cohort study was conducted among 136 COVID-19 adult patients at DMITC from January 1, 2020 to March 30, 2021. Data related to clinical, hematological profiles and socio-demographic factors were collected, entered into Epi data, and analyzed using STATA 14.2 software. Multivariable logistic regression was applied to determine the predictor variable and a p-value < 0.05 was considered significant. Results: Of 136 COVID-19 patients, 28.68% had died. The mean age of patients was 47.21± 1.29 years. The hematological profile of the patients revealed that 28% had abnormal leukocyte, 23% abnormal lymphocyte, 44.85% abnormal granulocyte, 22.06% abnormal monocyte, 30.15% abnormal RBC and 87% abnormal platelet counts. The prevalence of anemia was 13.24%. Conclusion: Leukocytosis (mainly granulocytosis and monocytosis) and lymphopenia, were the predominant abnormal findings of complete blood cell count (CBC) analysis of the patient’s blood. Most of the patients had abnormally low platelet counts. RBC count and hematocrit determination were the only significant predictors of death. The clinician could manage cases according to the hematological findings of the patients. Further experimental studies should be conducted to determine hematological parameter changes and the clinical outcome of the disease.