Unravelling the Link between the Gut Microbiome and Autoimmune Kidney Diseases: A Potential New Therapeutic Approach.

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.

Bacterial profile and extended spectrum beta lactamase screening of urinary tract infection among asymptomatic and symptomatic pregnant women attending antenatal care in ALERT Hospital, Addis Ababa, Ethiopia.

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.

Prevalence and Predictors of Pulmonary Tuberculosis among Prison Inmates in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

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 I2 and the Cochrane Q 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 (BMI < 18.5) (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.

Prevalence and predictors of dyslipidemia among HAART treated and HAART naive HIV positive clients attending Debre Tabor Hospital, Debre Tabor, Ethiopia.

Background: Highly active anti-retroviral therapy has been reported to be associated with a number of side effects in human immunodeficiency virus patients among which dyslipidemia isa common metabolic disorder. Methods: A Hospital based comparative cross-sectional study among 228 HIV positive patients was conducted from July to August 2020. Socio-demographic and clinical data were collected using structured questionnaires. Fasting venous blood sample was collected and analyzed for Lipid profiles. EDTA sample was analyzed for CD4+ T cell determination. Anthropometric measurement was done. Data were analyzed using SPSS version 22. Independent t-test was done. Logistic and binary regression was done. Result: A total of 228 HIV patients were enrolled in the study. Prevalence of dyslipidemia in HAART naive and HAART treated patients was 61 (53.5%) and 84 (73.7%), respectively. The prevalence of Total Cholesterol ≥200 mg/dl was 50% and 30%; High density lipoprotein cholesterol <40 mg/dl was 43.8% and 36%; Low density lipoprotein cholesterol ≥130 mg/dl was 48.3% and 28.1%; and Triglyceride ≥ 150 mg/dl 59.6% and 39% among HAART treated and HAART naive, respectively. Age greater than 40 years (AOR = 3.27, 95% C.I: 1.47-7.25), blood pressure ≥140/90 (AOR = 16.13, 95% C.I: 5.81-44.75), being on HAART (AOR = 2.73, 95% C.I: 1.35-5.53) and body mass index >25 kg/m2 (AOR = 1.92, 95% C.I: 1.20-4.81) were identified as determinants of dyslipidemia. Conclusion: The mean value of lipid profile was significantly higher among HAART treated as compared to those HAART naive HIV positive clients.

Hematological Profiles and Clinical Outcome of COVID-19 Among Patients Admitted at Debre Markos Isolation and Treatment Center, 2020: A Prospective Cohort Study.

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.

Phage Therapy: A Different Approach to Fight Bacterial Infections.

Phage therapy is one of the alternatives to treat infections caused by both antibiotic-sensitive and antibiotic-resistant bacteria, with no or low toxicity to patients. It was started a century ago, although rapidly growing bacterial antimicrobial resistance, resulting in high levels of morbidity, mortality, and financial cost, has initiated the revival of phage therapy. It involves the use of live lytic, bioengineered, phage-encoded biological products, in combination with chemical antibiotics to treat bacterial infections. Importantly, phages will be removed from the body within seven days of clearing an infection. They target specific bacterial strains and cause minimal disruption to the microbial balance in humans. Phages for medication must be screened for the absence of resistant genes, virulent genes, cytotoxicity, and their interaction with the host tissue and organs. Since they are immunogenic, applying a high phage titer for therapy exposes them and activates the host immune system. To date, no serious side effects have been reported with human phage therapy. In this review, we describe phage-phagocyte interaction, bacterial resistance to phages, how phages conquer bacterial resistance, the role of genetic engineering and other technologies in phage therapy, and the therapeutic application of modified phages and phage-encoded products. We also highlight the comparison of antibiotics and lytic phage therapy, the pros and cons of phage therapy, determinants of human phage therapy trials, phage quality and safety requirements, phage storage and handling, and current challenges in phage therapy.

Association of Cytotoxic T-Lymphocyte Antigen-4 Gene Polymorphism with Type 1 Diabetes Mellitus: In silico Analysis of Biological Features of CTLA-4 Protein on Ethiopian Population.

Background: T1DM is a chronic organ-specific T-cell-mediated autoimmune disease characterized by the selective destruction of ß-cells in the islets of Langerhans, resulting in insulin deficiency and hyperglycemia. Genes for cytotoxic T lymphocyte-associated antigen 4 have been hypothesized as possible contender genes for T1DM vulnerability. However, it has not been studied in the Ethiopian population yet. Objective: The aim of the study was to investigate CTLA-4 exon 1 was linked to A49G polymorphism with T1DM and its biological features of CTLA-4 among T1DM patients, in Ethiopia. Methods: A case-control study was done from December 2019 to March 2020 on 210 study participants (105 T1DM patients and 105 healthy controls). Polymerase Chain Reaction amplification with forward and reverse primers was followed by restriction fragment length polymorphism and gel electrophoresis to determine gene polymorphism. Bioinformatics data of SNP was retrieved from National Centers for Biotechnology Information databases. The chi-square test and logistic regression were used. Statistical significance was defined as a P-value of less than 0.05. Results: The CTLA-4 (+A49G) gene polymorphism was observed on 56 (26.7%) study participants, 39 (18.57%) of T1DM patients, and 17 (0.08%) were controls. In T1DM and controls, the frequency of the A allele was 73.3% and 89.5%, while the G allele was 26.7% and 10.5%, respectively. The G allele was found to be associated with T1DM (OR=3.1; 95% CI, 1.82 -5.32; P=0.001). Statistical analysis revealed an association between the likelihood of T1DM and GG genotype of the CTLA-4 (+A49G) gene polymorphism (OR=3.11; 95% CI, 1.37-10.90; P=0.01). Further in silico analyzed the SNP to assess its biological features. Conclusion: The study showed as CTLA-4 (+A49G) gene polymorphism is linked with T1DM in the Ethiopian population.

Aetiologies of acute undifferentiated febrile illness at the emergency ward of the University of Gondar Hospital, Ethiopia.

OBJECTIVE: Causes of acute febrile illness (AFI) often remain undetermined in developing countries, due to overlap of symptoms and limited available diagnostics. We aimed to assess the aetiology of AFI in adults in a referral hospital in northwest Ethiopia. METHODS: While all participants were tested for malaria by rapid diagnostic test (RDT), microscopy was only done on physician's request. Dengue virus (DENV) infections were detected using an RDT and ELISAs and dengue, yellow fever and chikungunya cases were identified by PCR. Bacterial aetiologies were investigated using blood culture and PCR. RESULTS: The aetiology of acute infection was identified for 20.5% of 200 patients enrolled. Eleven percent tested positive for Plasmodium, while microscopy was only requested for half of the identified malaria cases. For 4.0% of the Plasmodium-infected patients, an acute or past DENV (co-)infection was detected. We found 7.5% acute and 13.0% past DENV - all serotype 3 - infections. Bacterial infections were observed in 4.5% of the patients. CONCLUSION: Malaria is still a considerable aetiology of AFI and dengue is underrecognised. There are areas where both diseases occur concomitantly, and the DENV-3 serotype presumably spreads from Sudan to northern Ethiopia. As only 20.5% of the aetiologies were identified, a broader testing platform is required.

Immunomodulation of COVID-19 severity by helminth co-infection: Implications for COVID-19 vaccine efficacy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an emerging virus in late 2019 causing coronavirus disease 2019 (COVID-19), has caused a catastrophic effect, resulting in an unprecedented global crisis. The immunopathology of COVID-19 appears to be clearly associated with a dysregulated immune response leading to organ failure and death. Similarly, over two billion people worldwide are infected with helminth, with those living in low-middle-income countries disproportionately affected. Helminth infections have been shown to possess immunomodulatory effects in several conditions. Helminth co-infection in COVID-19 patients is one of the potential reasons for global attention to answer why COVID-19 severity is still lower in helminth endemic countries. Recent studies have shown that helminth endemic countries showed fewer cases and deaths so far and helminth co-infection might reduce the severity of COVID-19. Moreover, lessons from other diseases with helminth co-infection have been shown to substantially reduce vaccine efficacy that could also be implicated for COVID-19. This immunomodulatory effect of helminth has intended and unintended consequences, both advantageous and disadvantageous which could decrease the severity of COVID-19 and COVID-19 vaccine efficacy respectively. Herewith, we discuss the overview of COVID-19 immune response, immunomodulatory effects of helminth co-infections in COVID-19, lessons from other diseases, and perspectives on the efficacy of COVID-19 vaccines.

Neopterin: A Promising Candidate Biomarker for Severe COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has rapidly spread across the world since its first emergence in China in late 2019. It is a major public health concern with no effective treatct 3ments. The immunopathology of SARS-CoV-2 is associated with an excessive inflammatory response. Macrophage activation syndrome (MAS) is also associated with the severity of the disease in SARS-CoV-2-infected patients. Neopterin is a macrophage activation marker produced by monocytes and macrophages upon activation by interferon-gamma (IFN-γ). Neopterin is a well-established marker in a variety of diseases, and recent evidence indicates that it could be helpful in early prediction of the severity of COVID-19 disease and serve as a prognostic marker. Here, we outline the role of macrophage activation syndrome in the pathogenesis of SARS-CoV-2 and suggest that neopterin could be used as a biomarker for progression of COVID-19.

Evaluation of C-reactive protein and myxovirus resistance protein A to guide the rational use of antibiotics among acute febrile adult patients in Northwest Ethiopia.

OBJECTIVES: In low-resource settings, treatment is often given empirically without knowledge of the aetiology due to a lack of diagnostics. In the search for reliable rapid tests to guide treatment work-up, this study was performed to determine whether two biomarkers could differentiate bacterial from non-bacterial infections in acute febrile patients. METHODS: Adults with acute fever were recruited at a referral hospital in Ethiopia. The QuikRead Go test was used to quantify C-reactive protein (qCRP) and the FebriDx test was used for combined qualitative detection of the bacterial CRP marker with myxovirus resistance protein A (MxA), a viral biomarker. RESULTS: Of the 200 patients included in this study, most presented with 2-3 days of fever, headache, and joint pain. Antibiotics were prescribed for 83.5% and antimalarials for 36.5%, while a bacterial infection was only confirmed in 5% and malaria in 11%. The median qCRP level for confirmed bacterial infections was 128 mg/l. The FebriDx and QuikRead Go test had an overall agreement of 72.0%. CONCLUSIONS: An over-prescription of antibiotics for febrile patients was observed, even for those with low CRP levels and without a confirmed bacterial infection. The added value of the FebriDx was limited, while the combined use of rapid tests for qCRP and malaria should be considered for the management of acute febrile illness and antibiotic stewardship.