Differential expression of chemokine receptors on monocytes in TB and HIV S.

In the present study, we defined multiple chemokine receptors expressed by classical, intermediate and non-classical monocyte subsets in TB, HIV and TB/HIV co-infection and associate it with the perturbation of monocyte subsets due to the diseases. Peripheral blood mononuclear cells from TB+ (n = 34), HIV+ (n = 35), TB + HIV+ (n = 12), as well as TB-HIV- healthy controls (n = 39), were tested for monocyte phenotyping by flow cytometry. Frequencies of intermediate and non-classical monocytes were significantly higher in TB and/or HIV disease relative to healthy controls. CCR2 and CX3CR1 were significantly higher on monocytes in TB disease, whereas CCR4 and CCR5 were present at higher levels in HIV disease. TB/HIV co-infected patients exhibited CCR2, CCR5 and CX3CR1 levels intermediate to TB and HIV subjects, while CCR4 was at a higher level than HIV. Despite the increase in the expression of chemokine receptors due to disease conditions, chemokine receptors maintained their original expression pattern on monocyte subsets. Our data provided new insight into the disease-specific but not monocyte subsets-specific modulation of chemokine receptors in TB and HIV.

Reference Intervals for Absolute and Percentage CD4+ T Lymphocytes among an Apparently Healthy Population in Addis Ababa, Ethiopia.

Background: Reference intervals for clinical laboratory parameters differ based on several factors, including age, sex, genetic variation, and geographic location. This variation influences clinical decisions and treatment monitoring. Currently, Ethiopia has used adopted reference intervals from manufacturer values derived from non-Africans. Therefore, the aim this study was to determine reference intervals for absolute and percentage CD4+ T cells for an apparently healthy population in Addis Ababa, Ethiopia. Methods: A community-based cross-sectional study was conducted on 361 apparently healthy people in four subcities in Addis Ababa from January to June 2019. Sociodemographic and clinical data were collected using a structured questionnaire after informed consent had been obtained. Blood samples were collected and CD4+ T-lymphocyte enumeration performed using a BD FACSPresto near-patient CD4 counter. Data were entered and analyzed using SPSS 20. Reference intervals were determined by a nonparametric test estimating percentiles 2.5 (lower limit) and 97.5 (upper limit) with 95% CIs. P<0.05 was considered statistically significant. Results: A total of 337 (183 female and 154 male) healthy participants of median age 28 (IQR 17-35) years were included in the final analysis. Medians of absolute and percentage CD4+ T-cell counts (932.0 and 42.9, respectively) of female participants were significantly higher than male participants (802.5 and 38.7, respectively; P<0.05). Reference intervals for absolute CD4+ T-cell count and percentages in males were 483.8-1,310 cells/µL and 18.1-57.3 and in females 447.8-1,479.8 cells/µL and 25.6-58.9, respectively. Conclusion: The CD4+ T-count reference intervals established in this study showed some inconsistency from the manufacturer's provided values and other studies and also revealed sex differences, necessitating sex-specific locally established reference intervals.

Assessment of Serum Vitamin B12 and Folate Levels and Macrocytosis in Patients with Type 2 Diabetes Mellitus on Metformin Attending Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia: A Cross-Sectional Study.

BACKGROUND: Metformin is the first-line drug in the treatment of type 2 diabetes mellitus. Monitoring vitamin B12 deficiency associated with long-term and high-dose therapy is not a common practice in many clinical settings in Ethiopia. OBJECTIVE: The study aimed to measure levels of serum vitamin B12 and folate and to assess the macrocytic status of type 2 diabetes mellitus patients on metformin. METHODS: A cross-sectional study was conducted on 80 type 2 diabetes mellitus patients who had been on metformin for 5 months or more at the diabetic clinic of Tikur Anbessa Specialized Teaching Hospital. Serum vitamin B12 and folate levels were quantified by chemiluminescent immunoassays. Mean corpuscular volume was determined by complete blood count. Differences in vitamin B12 and folate levels and mean corpuscular volume between different groups were assessed using Kruskal-Wallis H and Mann-Whitney U tests. RESULTS: Vitamin B12 and folate deficiency were documented in 5% and 23.8% of participants, respectively, and 6.2% of patients were macrocytic. Levels of vitamin B12 and folate in patients who had been on metformin >1,500 mg/day ≥4 years were significantly lower those who had been on metformin 1,000-1,500 mg/day and <1,000 mg/day <4 years, respectively. CONCLUSION: Low serum vitamin B12 and folate levels and macrocytosis were found to be associated with prolonged metformin treatment.

Mitochondrial Dynamic Dysfunction as a Main Triggering Factor for Inflammation Associated Chronic Non-Communicable Diseases.

Mitochondria are organelles with highly dynamic ultrastructure maintained by flexible fusion and fission rates governed by Guanosine Triphosphatases (GTPases) dependent proteins. Balanced control of mitochondrial quality control is crucial for maintaining cellular energy and metabolic homeostasis; however, dysfunction of the dynamics of fusion and fission causes loss of integrity and functions with the accumulation of damaged mitochondria and mitochondrial deoxyribose nucleic acid (mtDNA) that can halt energy production and induce oxidative stress. Mitochondrial derived reactive oxygen species (ROS) can mediate redox signaling or, in excess, causing activation of inflammatory proteins and further exacerbate mitochondrial deterioration and oxidative stress. ROS have a deleterious effect on many cellular components, including lipids, proteins, both nuclear and mtDNA and cell membrane lipids producing the net result of the accumulation of damage associated molecular pattern (DAMPs) capable of activating pathogen recognition receptors (PRRs) on the surface and in the cytoplasm of immune cells. Chronic inflammation due to oxidative damage is thought to trigger numerous chronic diseases including cardiac, liver and kidney disorders, neurodegenerative diseases (Parkinson's disease and Alzheimer's disease), cardiovascular diseases/atherosclerosis, obesity, insulin resistance, and type 2 diabetes mellitus.

Prevalence of sexually transmitted infections (HIV, hepatitis B virus, herpes simplex virus type 2, and syphilis) in pregnant women in Ethiopia: Trends over 10 years (2005-2014).

OBJECTIVES: This study was performed to determine the trends in seroprevalence of four major sexually transmitted infections (STIs) (HIV, hepatitis B virus (HBV), herpes simplex virus type 2 (HSV-2), and syphilis) over a 10-year period (2005-2014) in pregnant women in Ethiopia. METHODS: Pregnant women (15-49 years old) who were enrolled in the antenatal care-based national HIV surveillance were included. Serological tests for HIV, HBV, HSV-2, and syphilis were done on serum/plasma samples. RESULTS: A total of 4887 pregnant women were included. Results showed a decline in prevalence of these STIs by 40-60% over the 10 years (2005-2014): HIV (10.5% to 5.5%), syphilis (2.5% to 1.1%), HBV (12.6% to 6.7%), and HSV-2 (47.5% to 28.5%). In 2014, 109/4887 (2.2%) women had triple infections. In 2005, 2007, and 2009, the prevalence of HSV-2 in the older age group (35-45 years) (47.1%, 47.4%, and 50.0%, respectively) was higher than that in the younger age group (15-24 years) (40.9%, 19.5%, and 20.2%, respectively). Age category (Chi-square=22.4, p<0.001), study sites/residence (Chi-square=135.2, p=0.001), and time/years (Chi-square=58.9, p=0.001) were associated with a positive HSV-2 test result. CONCLUSIONS: A decline in HIV, HBV, HSV-2, and syphilis of >40% was seen over the years in Ethiopia. However, an intermediate endemicity level of HBV and higher prevalence of HIV and HSV-2 by 2014, suggest the need to strengthen prevention strategy for STIs.

Host Gene Expression Kinetics During Treatment of Tuberculosis in HIV-Coinfected Individuals Is Independent of Highly Active Antiretroviral Therapy.

Background: Limitations in diagnostic tools to discriminate between active tuberculosis and latent Mycobacterium tuberculosis infection and for monitoring antituberculosis treatment responses are major challenges in tuberculosis control, especially in human immunodeficiency virus (HIV)-coinfected individuals. Methods: Expression levels of 105 immune-related genes were determined in 131 HIV-infected patients with active tuberculosis (n = 48), patients with latent M. tuberculosis infection (LTBI; n = 37), and controls with no M. tuberculosis infection (n = 46) in Addis Ababa, Ethiopia, using focused gene expression profiling with a dual-color reverse-transcription multiplex ligation-dependent probe amplification assay. Results: Within the cohort of HIV-positive subjects, the expression profiles of 7 genes at baseline (FCGR1A, RAB24, TLR1, TLR4, MMP9, NLRC4, and IL1B) could accurately discriminate between active tuberculosis and both latent and no M. tuberculosis infection, largely independently of (in)eligibility for highly active antiretroviral therapy (HAART). Six months after antituberculosis treatment, biomarker profiles of patients with tuberculosis became indistinguishable from those of patients with LTBI and controls. Importantly, host gene expression kinetics during antituberculosis treatment in HIV-coinfected individuals was found to be independent of HAART use. Conclusions: Blood transcriptomic profiles can potentially be used as biomarkers to discriminate the different clinical stages of tuberculosis in HIV-coinfected individuals and to monitor tuberculosis treatment responses in both HAART recipients and untreated individuals.

Tumor Lysis Syndrome in Patients with Hematological Malignancies.

Tumor lysis syndrome is a metabolic complication that may follow the initiation of cancer therapy. It commonly occurs in hematological malignant patients particularly non-Hodgkin's lymphoma and acute leukemia due to chemotherapy or spontaneously. It is characterized by a biochemical abnormality such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia and its clinical outcome is directly related to these biochemical abnormalities. Prevention and treatment of tumor lysis syndrome depend on immediate recognition of patients at risk. Therefore, identifying patients at risk and prophylactic measures are important to minimize the clinical consequences of tumor lysis syndrome. Patients with low risk should receive hydration and allopurinol. On the other hand patients with high risk should receive hydration and rasburicase in an inpatient setting. It is important to start therapy immediately, to correct all parameters before cancer treatment, to assess risk level of patients for TLS, and to select treatment options based on the risk level. In this review a comprehensive search of literatures was performed using MEDLINE/PubMed, Hinari, the Cochrane library, and Google Scholar to summarize diagnostic criteria, incidence, predicting factors, prevention, and treatment options for tumor lysis syndrome in patients with hematological malignancies.