CD4+ T cell count and HIV-1 viral load dynamics positively impacted by H. pylori infection in HIV-positive patients regardless of ART status in a high-burden setting.

BACKGROUND: There is a widespread co-infection of HIV and Helicobacter pylori (H. pylori) globally, particularly in developing countries, and it has been suggested that this co-infection may affect the course of HIV disease. However, the interplay between H. pylori infection and HIV disease progression is not fully elucidated. In this study, we investigated the effect of H. pylori co-infection on CD4+ T cell count and HIV viral load dynamics in HIV-positive individuals in a high co-endemic setting. METHODS: A comparative cross-sectional study was conducted among 288 HIV-positive and 175 HIV-negative individuals, both with and without H. pylori infection. Among HIV-positive participants, 195 were on antiretroviral therapy (ART) and 93 were ART-naïve. CD4+ T cell count and HIV-1 viral load were measured and compared between H. pylori-infected and -uninfected individuals, taking into account different HIV and ART status. RESULT: Our study demonstrated that individuals infected with H. pylori had a significantly higher CD4+ T cell count compared to uninfected controls among both HIV-negative and HIV-positive participants, regardless of ART therapy. Conversely, HIV/H. pylori co-infected participants had lower HIV-1 viral load than those without H. pylori infection. Linear regression analysis further confirmed a positive association between H. pylori infection, along with other clinical factors such as BMI, ART, and duration of therapy, with CD4+ T cell count while indicating an inverse relationship with HIV-1 viral load in HIV-positive patients. Additionally, factors such as khat chewing, age and WHO clinical stage of HIV were associated with reduced CD4+ T cell count and increased HIV-1 viral load. CONCLUSION: Our study demonstrates that H. pylori co-infection was associated with higher CD4+ T cell count and lower HIV-1 viral load in HIV-positive patients, regardless of ART status. These findings show a positive effect of H. pylori co-infection on the dynamics of HIV-related immunological and virological parameters. Further studies are needed to elucidate the underlying mechanisms of the observed effects.

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.

Alteration of Endocrine Hormones and Antibody Responses in Different Spectrum of Tuberculosis Disease.

Effective control of Mycobacterium tuberculosis (Mtb) infection is mediated by multifaceted factors that involve both the endocrine and immune system. Profiling hormones and antibodies in different stages of TB provides insight in the pathogenesis of the disease. In this study, we profiled endocrine hormones (dehydroepiandrosterone (DHEA), cortisol, testosterone, estradiol, growth hormone and leptins) and Mtb strain H37RV lipoarabinomannan (LAM)-specific antibody levels in plasma samples, collected from pulmonary TB (PTB) patients, TB lymphadenitis (TBLN) patients and latently infected (QFT-positive) or uninfected (QFT-negative) apparently healthy individuals using ELISA. Plasma levels of leptin and DHEA were significantly low in PTB and TBLN patients compared to healthy controls (P<0.0001 and P=0.02, respectively), whereas these levels significantly increased following anti-TB treatment (P=0.002 and P=0.0001, respectively) among TB patients. The levels of estradiol and testosterone significantly improved following anti-TB treatment (P=0.03 and P=0.0003, respectively), whereas cortisol and growth hormones declined significantly (P <0.05). Similarly, LAM-specific IgG, IgM and IgA were significantly higher in PTB patients compared to other groups, whereas levels of IgG1 subtype were significantly higher among LTBI groups compared to both TB patients and QFT-negative individuals (P<0.0001). Overall, we observed significantly variable levels of endocrine hormones as well as immunoglobulins across the spectrum of TB illness and such profiling has a significant contribution in selection of effective biomarkers that have roles in TB treatment monitoring or diagnostics. Although this study did not show a functional association between hormones and antibodies, alterations in the levels of these biomarkers suggest the key roles these markers play in TB pathogenesis.

Opportunistic Cryptococcal Antigenemia in the HAART Era at HIV Epidemic Settings of Northwest Ethiopia.

BACKGROUND: Cryptococcus neoformans is a frequent opportunistic infection in patients with the acquired immunodeficiency syndrome. While the advent of ART reduces the occurrence of cryptococcal meningitis in HIV patients, cryptococcal disease remains a leading cause of morbidity and mortality in the developing world especially in sub-Saharan Africa which is the epicenter of HIV. This study aimed to assess the cryptococcal antigenemia, CD4+ Th cell counts, HIV RNA viral load, and clinical presentations among HIV-positive patients in Northwest Ethiopia. METHOD: A total of two hundred (200) HIV-positive patients were recruited for this study. Cryptococcus antigenemia prevalence in plasma samples of HIV-positive patients was determined by using Antigen lateral flow assay (CrAg-LFA) also, and CD4+ Th cell counts and HIV-RNA levels were quantified from blood specimen. Patients' demographic data, clinical manifestation, and concurrent opportunistic infection were recorded. RESULT: The sex distributions of study participants were 105(52.5%) male and 94(47.5%) female with an age range of 15-65 (mean 39.42 ± 9) years. All patients had a CD4+ T-cell count <100 cells/µl with the median 54 cells/µl and median HIV-RNA viral load 2.16 × 105 RNA copies/ml (50-3.66 × 105 RNA copies/ml); the prevalence of cryptococcal antigenemia was found to be 4% in HIV-positive patients. More than half and two third of CrAg-positive patients had a CD4 count <25 cells/µl and HIV viral load >10,000 copies/ml, respectively, as well; Tuberculosis, Candidiasis, and herpes zoster are the most often observed concurrent infections while cryptococcal antigenemia is significantly associated with oral candidiasis (p < 0.001). CONCLUSION: Although the advent of ART, early diagnosis of cryptococcosis, and application of antifungal interventions, HIV-induced cryptococcal antigenemia positivity in HIV infected individuals is still the countries' big challenge. Thus, stringent follow-up and case management should be considered.

Validation of in-house liquid direct agglutination test antigen: the potential diagnostic test in visceral Leishimaniasis endemic areas of Northwest Ethiopia.

BACKGROUND: Visceral leishmaniasis in Ethiopia is a re-emerging threat to public health, with increased geographical distribution and number of cases. It is a fatal disease without early diagnosis and treatment; thus, the availability of affordable diagnostic tools is crucial. However, due to delays caused by import regulations, procurement and late delivery of imported test kits, accessibility remains a problem in the control program. Therefore, we aimed to produce and evaluate the performance of an in-house liquid (AQ) direct agglutination test (DAT) antigen. RESULT: The AQ-DAT was produced at the Armauer Hansen Research Institute, using Leishmania donovani strain (MHOM/ET/67/L82). Sera from 272 participants; 110 microscopically confirmed cases of VL, 76 apparently healthy and 86 patients who had infectious disease other than VL were tested with AQ-DAT, and standard kits: Freeze-dried DAT (FD-DAT) and rK39. Taking microscopy as a gold standard; the sensitivity and specificity of the AQ-DAT were 97.3 and 98.8%, respectively. It had high degrees of agreement (k > 0.8), with a significant (P < 0.05) correlation compared to microscopy, FD-DAT, and rK39. CONCLUSION: Although further standardization is required, the in-house AQ-DAT could improve diagnostic accessibility, minimize intermittent stock outs and strengthen the national VL control program.

T lymphocyte subpopulations and intestinal helminthes profile among tuberculosis patients co-infected with HIV before and after anti tubercular treatment at University of Gondar Hospital, Northwest Ethiopia.

BACKGROUND: Tuberculosis continues to be a health problem of both developed and developing countries, and its incidence has currently increased due to HIV induced immune suppression. HIV-co-infection decreases the total number of CD4+ T cells since the virus preferentially replicates with in activated CD4+ T cells and macrophages, resulting in the disruption of granuloma to contain M. tuberculosis. In this study, we investigated the change in T lymphocyte subpopulations before and after anti-tubercular treatment and the effect of intestinal parasites on the cell populations of tuberculosis patients before the initiation of anti TB treatment. METHOD: A prospective cohort study was conducted in the outpatient TB Clinic, University of Gondar hospital between January 2014 and August 2015. Blood samples were collected from 80 newly diagnosed TB patients with and without HIV co-infection. The mean CD4+ and CD8+ T lymphocyte counts of the patients were assessed before and after the course of anti-TB treatment. The mean values of T lymphocytes of TB, TB/HIV co-infected patients and of the control groups were compared. Data was analyzed by SPSS version 16 and the graph pad prism software. RESULTS: A total of 80 tuberculosis patients 40 of whom were co-infected with HIV participated in our study. The mean CD4 + T lymphocytes counts of the TB/HIV cohort were 354.45 ± 138cell/µl, and the mean CD8+ cell counts were 926.82 ± 384cell/µl. There were significant changes in the mean CD4+ and CD8+ T cell counts after the course of anti-TB treatment in both groups of patients(p < 0.05). However, no statistically significant differences were observed in the mean CD4 + and CD8+ T cell counts of helminthes infected and non-infected patients (P > 0.05). CONCLUSION: We found significantly lower CD4+ T cell counts among TB infected HIV negative patients compared with controls who showed that TB was the cause of non-HIV-associated declination of circulating CD4 counts, and the reduction was reversible with anti-tubercular treatment in both HIV-negative and ART naïve TB-HIV co-infected patients.

TNF-α (-308) Gene Polymorphism and Type 2 Diabetes Mellitus in Ethiopian Diabetes Patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder resulting from insulin insufficiency or function. Predisposing factors for T2DM are mainly genetic and environmental. Genetic polymorphism of cytokines like tumor necrosis factor-alpha (TNF-α) is suggestive of interference with insulin-sensitive glucose uptake and induces insulin resistance that ultimately could lead to T2DM. In this study, we assessed the effect of TNF-α (-308) G/A gene polymorphism and its association with the development of T2DM in an Ethiopian population. METHODS: An institutional-based cross-sectional study was conducted on study subjects with T2DM and non-diabetic healthy controls. DNA was extracted and genotyping was carried out by using amplification refractory mutation system polymerase chain reaction. A genetic-polymorphism on TNF-α (-308) G/A with T2DM was evaluated by logistic regression and Student's t-test. A P-value <0.05 was considered as statistically significant. RESULTS: In the present study, we observed a significant association between T2DM and TNF-α (-308) gene polymorphism's GG genotype [χ2 test P = 0.005, OR (95% CI) =2.667 (1.309-5.45d8)]. In contrast, no statistically significant differences were observed in the frequencies of genotypes AA and AG (χ2 test P=0.132 and 0.067, respectively). Moreover, T2DM individuals had higher concentrations of lipid profiles for those carrying the TNF-α (-308) GG genotype as compared to the control group. CONCLUSION: TNF-α (-308) genetic polymorphism may be implicated in the genetic susceptibility for, as well as the development of T2DM and lipid metabolism in the Ethiopian population. Therefore, a large-scale study and early screening of TNF-α (-308) genetic polymorphism may help in early management and control of diabetes and related outcomes.

Immunological Impacts of Diabetes on the Susceptibility of Mycobacterium tuberculosis.

The interaction between diabetes and major world infections like TB is a major public health concern because of rapidly rising levels of diabetes. The dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a major global public health problem. Diabetes mellitus is a major risk factor for the development of active and latent tuberculosis. Immune mechanisms contributing to the increased susceptibility of diabetic patients to TB are due to the defects in bacterial recognition, phagocytic activity, and cellular activation which results in impaired production of chemokines and cytokines. The initiation of adaptive immunity is delayed by impaired antigen-presenting cell (APC) recruitment and function in hyperglycemic host, which results in reduced frequencies of Th1, Th2, and Th17 cells and its secretion of cytokines having a great role in activation of macrophage and inflammatory response of tuberculosis. In addition, impaired immune response and killing of intracellular bacteria potentially increase bacterial load, chronic inflammation, and central necrosis that facilitate bacterial dissemination and miliary tuberculosis. Understanding of the immunological and biochemical basis of TB susceptibility in diabetic patients will tell us the rational development of implementation and therapeutic strategies to alleviate the dual burden of the diseases. Therefore, the aim of this review was focused on the association between diabetes and tuberculosis, focusing on epidemiology, pathogenesis, and immune dysfunction in diabetes mellitus, and its association with susceptibility, severity, and treatment outcome failure to tuberculosis.

Comparison of RPR and ELISA with TPHA for the Diagnosis of Syphilis: Implication for Updating Syphilis Point-of-Care Tests in Ethiopia.

BACKGROUND: Syphilis is a sexually transmitted disease (STD) caused by the spirochete Treponema pallidum, and it persists to be a major public health problem in Africa, including Ethiopia. Syphilis diagnosis is made by either nontreponemal or treponemal approaches, though in developing countries the diagnosis relies mostly on nonspecific tests due to several reasons. Thus, the objective of this study was to assess the sensitivity, specificity, predictive values, and agreement of rapid plasma reagin (RPR) and enzyme-linked immunosorbent assay (ELISA) with Treponema pallidum hemagglutination assay (TPHA) as a gold standard for the diagnosis of syphilis. RESULTS: The sensitivity, specificity, and positive and negative predictive values of ECOTEST-RPR were 100%, 80.8%, 76.2%, and 100%, respectively. However, the sensitivity, specificity, and positive and negative predictive values of DIALAB-ELISA were 98.4%, 94.9%, 92.3%, and 98.9%, respectively. The agreement between DIALAB-ELISA and Randox-TPHA was excellent (kappa value: 0.96) as compared to ECOTEST-RPR and Randox-TPHA assay (kappa value: 0.88). CONCLUSION: We found a characteristically variable performance of DIALAB-ELISA test and the currently available traditional ECOTEST-RPR test in the study area. The use of ECOTEST-RPR as a diagnostic test is confronted by its false positivity. Thus, neither the ECOTEST-RPR nor the DIALAB-ELISA test stands on its own to be used either as screening or confirmatory test for syphilis diagnosis. Consequently, thorough studies should be conducted aiming on a change of the current diagnostic scheme in the community.

Prevalence of Intestinal Parasites and Associated Factors among Pulmonary Tuberculosis Suspected Patients Attending University of Gondar Hospital, Gondar, Northwest Ethiopia.

INTRODUCTION: Intestinal parasitic infections are among the major public health problems in developing countries. Hence, it is significant to explore coinfection with intestinal parasites and pulmonary tuberculosis because coinfection increases the complexity of control and prevention of pulmonary tuberculosis and parasitic diseases. OBJECTIVE: To assess the prevalence of intestinal parasites among pulmonary tuberculosis suspected patients. METHOD: Institutional based cross-sectional study was conducted at University of Gondar Hospital from March to May, 2017. Stool samples were taken from each participant and examined by direct microscopy and concentration technique. Descriptive statistics was performed and chi-square test was used to show the association between variables. P values of <0.05 were considered statistically significant. RESULTS: Intestinal parasites were detected in 50 (19.6%) among a total of 256 pulmonary tuberculosis suspected patients who were included in the study, whereas the prevalence of pulmonary tuberculosis was 16.8% (43/256). Pulmonary tuberculosis and intestinal parasite coinfection was detected in 5 (2.0%) of the participants. The most prevalent intestinal parasites infection in this study was Ascaris lumbricoides, 15 (5.85%), followed by Entamoeba histolytica/dispar, 14 (5.46%), and Hookworm, 13 (5.1%). CONCLUSION: The prevalence of intestinal parasites and their coinfection rate with pulmonary tuberculosis among pulmonary tuberculosis suspected patients were considerable.