Protein Expression of TLR2, TLR4, and TLR9 on Monocytes in TB, HIV, and TB/HIV.

Toll-like receptors (TLRs) have a critical role in recognizing pathogenic patterns and initiating immune responses against TB and HIV. Previously, studies described the gene expression of TLRs in patients with TB and HIV. Here, we demonstrated TLRs protein expressions and their association with clinical status and plasma markers in TB, HIV, and TB/HIV coinfection. The phenotyping of TLR2, TLR4, and TLR9 on CD14+ monocytes and their subsets were determined by multicolor flow cytometry. Host plasma biomarkers and microbial indices were measured using Luminex Multiplex assay and standard of care tools, respectively. TLR2 expression significantly enhanced in TB, slightly increased in HIV but slightly reduced in TB/HIV coinfection compared to apparently health controls (HC). On the other hand, TLR4 expression was significantly increased in TB, HIV, and TB/HIV compared to HC. Expression of TLR4 was equally enhanced on classical and intermediate monocytes while higher TLR2 expression on intermediate than classical monocytes. TLR4 had a positive correlation pattern with plasma biomarkers while TLR2 had an inverse correlation pattern. TLR4 is associated with disease severity while TLR2 is with the immune-competent status of patients. Our findings demonstrated that the pattern of TLR expression is disease as well as monocyte subset specific and distinct factors drive these differences.

Seroprevalence of SARS-CoV-2 and Hepatitis B Virus Coinfections among Ethiopians with Acute Leukemia.

SARS-CoV-2 and blood-borne viral coinfections are well reported. Nevertheless, little is known regarding the seroprevalence of SARS-CoV-2 and coinfection with blood-borne viruses in hematologic malignancy patients in Ethiopia. We aimed to assess the seroprevalence of SARS-CoV-2 and associated infections with hepatitis B and other viruses among adolescent and adult acute leukemia patients at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. A cross-sectional study was conducted from July 2020 to June 2021. Blood samples were tested for the presence of anti-SARS-CoV-2, HBV, HCV, and HIV with ELISA kits and occult hepatitis B infection with a real-time polymerase chain reaction assay. Out of a total 110 cases, the SARS-CoV-2 seroprevalence was 35.5%. The prevalence showed a significant increment from July 2020 to the end of June 2021 (p = 0.015). In 22.7% and 2.7% of leukemia cases, HBV and HIV, respectively, were detected. No HCV was identified. The rate of SARS-CoV-2 coinfection with HBV and HIV was 28% (11/39) and 2.6% (1/39), respectively; however, there was no statistically significant association between SARS-CoV-2 seropositivity with HBV and HIV (p > 0.05). There is a need for viral screening in leukemia cases to monitor infections and inform management.

High rate of high-risk human papillomavirus among benign and breast cancer patients in Ethiopia.

INTRODUCTION: There have been numerous studies that showed the presence of human papillomavirus (HPV) in breast cancer; nonetheless, there is ongoing debate regarding their association. Given few studies in Ethiopia, we aimed to investigate the magnitude of HPV infection in Ethiopian breast cancer patients. METHODS: A total of 120 formalin-fixed paraffin-embedded (FFPE) tissue blocks were obtained, and basic demographic, clinical, and histological data were collected from medical records. DNA was extracted from archived FFPE breast tissue specimens using GeneRead DNA FFPE Kit. The AnyplexTM II HPV28 Detection Kit (Seegene, Korea) was used to detect HPV by following the manufacturer's instructions. The SPSS Version 25 was used to enter and analyze data. RESULTS: Among the 120 study participants; HPV (both high-risk and low-risk) was detected in 20.6% of breast cancer and 29.6% of non-malignant breast tumors. The most common genotype was the high-risk HPV 16 genotype. The frequency of HPV was nearly 10-fold higher in estrogen receptor-positive than ER-negative breast cancer. The percentage of HPV in the luminal (luminal A and luminal B) breast cancer subtypes was also much higher than in the non-luminal subtypes (HER-2 enriched and triple-negative breast cancer). CONCLUSION: This study did not find a significant difference in HPV expression between breast cancer and non-malignant breast tumors; however, the higher percentage of HPV in ER-positive compared to ER-negative breast cancer warrants further attention.

Clinical and Imaging Characteristics of Smear Negative Pulmonary Tuberculosis Patients: A Comparative Study.

Background: Prevalence surveys in Ethiopia indicate smear negative pulmonary tuberculosis (SNPTB) taking the major share of the overall TB burden. It has also been a diagnostic dilemma worldwide leading to diagnostic delays and difficulty in monitoring treatment outcomes. This study determines and compares the clinical and imaging findings in SNPTB and smear positive PTB (SPPTB). Methodology. A case-control study was conducted on 313 PTB (173 SNPTB) patients. Data and sputum samples were collected from consented patients. Smear microscopy, GeneXpert, and culture analyses were performed on sputum samples. Data were analyzed using Stata version 17; a P value < 0.05 was considered statistically significant. Results: Of the 173 SNPTB patients, 42% were culture positive with discordances between test results reported by health facilities and Armauer Hansen Research Institute laboratory using concentrated smear microscopy. A previous history of TB and fewer cavitary lesions were significantly associated with SNPTB. Conclusions: Though overall clinical presentations of SNPTB patients resemble those seen in SPPTB patients, a prior history of TB was strongly associated with SNPTB. Subject to further investigations, the relatively higher discrepancies seen in TB diagnoses reflect the posed diagnostic challenges in SNPTB patients, as a higher proportion of these patients are also seen in Ethiopia.

Evidence for immune activation in pathogenesis of the HLA class II associated disease, podoconiosis.

Available evidences suggest that podoconiosis is triggered by long term exposure of bare feet to volcanic red clay soil particles. Previous genome-wide studies in Ethiopia showed association between the HLA class II region and disease susceptibility. However, functional relationships between the soil trigger, immunogenetic risk factors and the immunological basis of the disease are uncharted. Therefore, we aimed to characterise the immune profile and gene expression of podoconiosis patients relative to endemic healthy controls. Peripheral blood immunophenotyping of T cells indicated podoconiosis patients had significantly higher CD4 and CD8 T cell surface HLA-DR expression compared to healthy controls while CD62L expression was significantly lower. The levels of the activation markers CD40 and CD86 were significantly higher on monocytes and dendritic cell subsets in patients compared to the controls. RNA sequencing gene expression data indicated higher transcript levels for activation, scavenger receptors, and apoptosis markers while levels were lower for histones, T cell receptors, variable, and constant immunoglobulin chain in podoconiosis patients compared to healthy controls. Our finding provides evidence that podoconiosis is associated with high levels of immune activation and inflammation with over-expression of genes within the pro-inflammatory axis. This offers further support to a working hypothesis of podoconiosis as soil particle-driven, HLA-associated disease of immunopathogenic aetiology.

Pneumococcal colonization and coinfecting respiratory viruses in children under 5 years in Addis Ababa, Ethiopia: a prospective case-control study.

A comprehensive understanding of the dynamics of Streptococcus pneumoniae colonization in conjunction with respiratory virus infections is essential for enhancing our knowledge of the pathogenesis and advancing the development of effective preventive strategies. Therefore, a case-control study was carried out in Addis Ababa, Ethiopia to investigate the colonization rate of S. pneumoniae and its coinfection dynamics with respiratory viruses among children under the age of 5 years. Samples from the nasopharyngeal and/or oropharyngeal, along with socio-demographic and clinical information, were collected from 420 children under 5 years old (210 cases with lower respiratory tract infections and 210 controls with conditions other than respiratory infections.). A one-step Multiplex real-time PCR using the Allplex Respiratory Panel Assays 1-4 was performed to identify respiratory viruses and bacteria. Data analysis was conducted using STATA software version 17. The overall colonization rate of S. pneumoniae in children aged less than 5 years was 51.2% (215/420). The colonization rates in cases and controls were 54.8% (115/210) and 47.6% (100/210), respectively (p = 0.14). Colonization rates were observed to commence at an early age in children, with a colonization rate of 48.9% and 52.7% among infants younger than 6 months controls and cases, respectively. The prevalence of AdV (OR, 3.11; 95% CI [1.31-8.19]), RSV B (OR, 2.53; 95% CI [1.01-6.78]) and HRV (OR, 1.7; 95% CI [1.04-2.78]) tends to be higher in children who tested positive for S. pneumoniae compared to those who tested negative for S. pneumoniae. Further longitudinal research is needed to understand and determine interaction mechanisms between pneumococci and viral pathogens and the clinical implications of this coinfection dynamics.

High rate of non-vaccine targeted high-risk HPV genotypes circulate among women in Eastern Ethiopia.

The World Health Organization [WHO] recommends a genotype-specific human papillomavirus [HPV] vaccination as a primary prevention strategy to control the burden of cervical cancer globally. In Ethiopia, where the non-vaccine-targeted HPV genotypes have not been adequately studied, a vaccination initiative was launched in 2018 targeting HPV-6,-11, -16, and -18 for girls aged 14-18 years. The co-existence of both vaccine-targeted and non-targeted genotypes is a serious concern, as it can accelerate cancer progression. Therefore, this study was conducted to determine the prevalence of non-vaccine-targeted HPV genotypes and assess the level of multiple infections with other genotypes in eastern Ethiopia. A health facility-based cross-sectional study including 110 women with positive HPV DNA results was conducted from April to August 2021. A structured questionnaire to collect demographic and clinical data was used. Cervical swabs were collected using L-shaped FLOQSwabs. Women's cytological profile was determined based on Pap smear test results. An automated nucleic acid extraction system using STARMag 96 ProPrep Universal Extraction Kit was utilized following the manufacturer's protocol. An amplification assay in real-time was employed to amplify and identify the HPV Late 1 [L1] gene, which is utilized for genotyping purposes. Following this, the collected data was entered into Epi data version 3.1 software, and the analysis was performed using STATA version 14. A total of 110 women [age range 30-60 years, mean age = 36.5 years and SD ± 6.9] had positive HPV DNA results and were included in the study. Among these, 108 women had valid co-testing [Pap test and HPV DNA test] results for further analysis, and the results of the remaining 2 women were rejected. Overall, the prevalence of non-vaccine-targeted HPV was 56 (51.8%, 95%CI [0.42, 0.61]), of which 28 women (25.4%, 95%CI [0.18, 0.34]) had a single non-vaccine HPV genotype infection. The remaining 29 women (26.4%, 95% CI: 0.190-0.355) experienced multiple infections. The non-vaccine-targeted genotypes of HPV-35 accounted for 11 cases (10%, 95%CI [0.06, 0.17]), HPV-68 was detected in 9 women (8.2%, 95%CI [0.04, 0.15]), HPV-56 and HPV-66 were both found in 8 cases each (7.3%, 95%CI [0.04, 0.14]) of the total. In addition, out of these 108 women, 93 (86.1%, 95%CI [0.78, 0.91]) had low-grade squamous intraepithelial lesions, 13 (12%, 95%CI [0.07, 0.20]) no intraepithelial lesion or malignancy, and two (1.9%, 95%CI [0.01, 0.07]) high-grade squamous intraepithelial lesions. Furthermore, there was no statistical difference [p = 0.755] between vaccine-targeted and non-vaccine-targeted genotypes as the primary cause of cervical lesions. In conclusion, the findings of the present study highlight the existence of a notable prevalence of multiple infections caused by non-vaccine-targeted HPV genotypes. Therefore, it is recommended that both the Federal and regional health bureaus to evaluate the range of hr HPV genotypes protected by the current HPV vaccine and explore the option of transitioning from the quadrivalent HPV vaccine to a novavalent vaccine that includes seven high-risk HPV genotypes.

Multi-country collaborative citizen science projects to co-design cardiovascular disease prevention strategies and advocacy: findings from Ethiopia, Malawi, Rwanda, and South Africa.

BACKGROUND: Cardiovascular diseases (CVD) were responsible for 20.5 million annual deaths globally in 2021, with a disproportionally high burden in sub-Saharan Africa (SSA). There is growing evidence of the use of citizen science and co-design approaches in developing interventions in different fields, but less so in the context of CVD prevention interventions in SSA. This paper reports on the collaborative multi-country project that employed citizen science and a co-design approach to (i) explore CVD risk perceptions, (ii) develop tailored prevention strategies, and (iii) support advocacy in different low-income settings in SSA. METHODS: This is a participatory citizen science study with a co-design component. Data was collected from 205 participants aged 18 to 75 years in rural and urban communities in Malawi, Ethiopia and Rwanda, and urban South Africa. Fifty-one trained citizen scientists used a mobile app-based (EpiCollect) semi-structured survey questionnaire to collect data on CVD risk perceptions from participants purposively selected from two communities per country. Data collected per community included 100-150 photographs and 150-240 voice recordings on CVD risk perceptions, communication and health-seeking intentions. Thematic and comparative analysis were undertaken with the citizen scientists and the results were used to support citizen scientists-led stakeholder advocacy workshops. Findings are presented using bubble graphs based on weighted proportions of key risk factors indicated. RESULTS: Nearly three in every five of the participants interviewed reported having a relative with CVD. The main perceived causes of CVD in all communities were substance use, food-related factors, and litter, followed by physical inactivity, emotional factors, poverty, crime, and violence. The perceived positive factors for cardiovascular health were nutrition, physical activity, green space, and clean/peaceful communities. Multi-level stakeholders (45-84 persons/country) including key decision makers participated in advocacy workshops and supported the identification and prioritization of community-specific CVD prevention strategies and implementation actions. Citizen science-informed CVD risk screening and referral to care interventions were piloted in six communities in three countries with about 4795 adults screened and those at risk referred for care. Health sector stakeholders indicated their support for utilising a citizen-engaged approach in national NCDs prevention programmes. The citizen scientists were excited by the opportunity to lead research and advocacy. CONCLUSION: The collaborative engagement, participatory learning, and co-designing activities enhanced active engagement between citizen scientists, researchers, and stakeholders. This, in turn, provided context-specific insights on CVD prevention in the different SSA settings.

Evidence for distinct mechanisms of immune suppression in EBV-positive and EBV-negative Hodgkin lymphoma.

Epstein Barr Virus (EBV) has been recognized for its ability to transform B lymphocytes and for its association with different types of cancers including Hodgkin lymphoma. In addition, EBV may also modulate the microenvironment of HL. In this study, we aimed to investigate the prevalence of EBV among HL cases in Ethiopia and to assess the tissue cellular composition of EBV-related and EBV-unrelated cases. We constructed a tissue microarray (TMA) of 126 consecutive cases of classical HL (CHL) and nodular lymphocyte predominant HL (NLPHL) from a tertiary cancer centre, Tikur Anbessa Hospital, Addis Ababa, Ethiopia, and evaluated a panel of immunohistochemical markers. The quantification of immune cells was performed using HALO 2.3, a platform for image analysis from Indica Lab Inc. A total of 77/126 (61.1%) of HL cases expressed LMP1/EBER. Infiltration of CD8+, T-bet+ and FoxP3+ cells was higher in the microenvironment of EBV-related CHL, with P values of <0.001, <0.001 and <0.016, respectively. In contrast, the expression of PD1 was higher in the microenvironment of EBV-unrelated CHL cases (P < 0.001). Unlike in Western countries, the majority of HL cases in Ethiopia were associated with EBV. As FoxP3+ and PD1-expressing cells are thought to participate in down regulation of the immune response by different mechanisms, this finding highlights the previously unrecognized possibility that distinct immunosuppressive mechanisms may be ongoing within EBV positive and negative HL types. This may have important prognostic and therapeutic implications.

Immunohistochemistry-derived subtypes of breast cancer distribution in four regions of Ethiopia.

Purpose: Different biological characteristics, therapeutic responses, and disease-specific outcomes are associated with different molecular subtypes of breast cancer (BC). Although there have been different studies on BC in the Ethiopian capital city of Addis Ababa, there have been few studies in other parts of the nation, and none have evaluated biological characteristics in other locations in the context of the extensive ethnic and genetic diversity found in Ethiopia. This study was carried out to evaluate the distribution of immunohistochemistry (IHC) subtypes of BCs throughout four Ethiopian regions. Methods: A total of 227 formalin-fixed paraffin-embedded (FFPE) tissue blocks were collected from tertiary hospitals in four Ethiopian regions between 2015 and 2021. The IHC staining was performed for subtyping, ER, PR, HER2, and Ki-67 proliferation markers. Results: The mean age at diagnosis was 43.9 years. The percentage of ER and PR-negative tumors were 48.3% and 53.2%, respectively. The IHC subtypes showed the following distribution: 33.1% triple-negative breast cancer (TNBC), 27.6% luminal B, 25.2% luminal A, and 14.1% HER2 enriched. In multiple logistic regression analysis, grade III and HER2 positivity were associated with larger tumor size, and also originating from Jimma compared to Mekele. Conclusion: Patients with ER-negative, PR-negative, and TNBC were found in 48.3%, 53.2%, and 33.1% of cases, respectively, showing that half the patients could potentially benefit from endocrine treatment. A considerably high prevalence of TNBC was reported in our study, demanding additional research that includes genetic predisposition factors. Additionally, aggressive tumors were found in a high percentage of younger age groups, which must be considered when planning personalized treatment strategies.

Loss to Follow-up and Death Among Individuals With Newly Diagnosed Human Immunodeficiency Virus Receiving Dolutegravir-Based First-Line Antiretroviral Treatment in Eastern Ethiopia: Implications for 95% United Nations Targets.

Background: Loss to follow-up (LTFU) and death are unfavorable outcomes of human immunodeficiency virus (HIV) treatment. This study aimed to identify the predictors of LTFU and death among individuals with newly diagnosed HIV receiving dolutegravir (DTG)-based first-line antiretroviral treatment (ART) in eastern Ethiopia. Methods: A multisite prospective cohort study was carried out between October 2020 and July 2022. New case patients who started ART were enrolled consecutively and then followed up for the next 6 months. A structured questionnaire and checklists were used to collect data. HIV viral load was determined using the Abbott RealTime HIV-1 assay. Bivariable and multivariable logistic regression models were used to identify baseline factors associated with the outcomes. Results: A total of 235 people with newly diagnosed HIV were enrolled; 16.6% (95% confidence interval, 12.3%-21.9%) were lost to follow-up, and 5.9% (3.5%-9.8%) died within 6 months of follow-up. Baseline World Health Organization clinical stage I (adjusted odds ratio, 3.93 [95% confidence interval, 1.34-11.57]), low viral load (3.67 [1.09-12.36]), and body weight (1.04 [1.01-1.07]) were predictors of LTFU, whereas nonfunctional status (10.02 [1.9-51.3]) was the only factor associated with death. Conclusions: LTFU and death rates among patients with DTG were relatively high, accounting for roughly a quarter of the attrition of people with newly diagnosed HIV from ART care and services. Thus, targeted interventions are required to reduce LTFU and death among individuals with HIV on ART. Further investigation is necessary to evaluate the long-term effects of DTG-based regimens on LTFU and its impact on HIV mortality rates, and qualitative research, specifically tracing LTFU, is recommended.

The expression of matrix metalloproteinase 2, 9 and 11 in Ethiopian breast cancer patients.

INTRODUCTION: Matrix metalloproteinases (MMPs) play a pathophysiological role in cancer initiation and progression. Numerous studies have examined an association between MMP-2, MMP-9, and MMP-11 expression and clinicopathological characteristics of breast cancer (BC); however, no research has been done on the MMP expression levels in BC cases from Ethiopia. MATERIALS AND METHODS: A total of 58 formalin-fixed paraffin-embedded breast tissue samples encompassing 16 benign breast tumors and 42 BC were collected. The RNA was extracted and quantitative reverse-transcription PCR was performed. GraphPad Prism version 8.0.0 was used for statistical analysis. RESULTS: The MMP-11 expression levels were significantly higher in breast cancer cases than in benign breast tumors (P = 0.012). Additionally, BC cases with positive lymph nodes and ER-positive receptors had higher MMP-11, MMP-9, and MMP-2 expression than cases with negative lymph nodes and ER-negative, respectively. The MMP-11 and MMP-9 expressions were higher in grade III and luminal A-like tumors than in grade I-II and other subtypes, respectively. CONCLUSION: The MMP-11 expression was higher in BC than in benign breast tumors. Additionally, MMP-11, MMP-9, and MMP-2 were higher in BC with positive lymph nodes and estrogen receptors. Our findings suggest an important impact of MMPs in BC pathophysiology, particularly MMP-11.

Virological Non-Suppression among Newly Diagnosed HIV-Positive Individuals on Dolutegravir-Based Antiretroviral Treatment in Eastern Ethiopia: Follow-Up Study.

There have been limited studies linking baseline factors, including the viral load (VL) test, with virological non-suppression since the introduction of dolutegravir (DTG)-based regimens as first-line antiretroviral treatment (ART) in Ethiopia. This study aimed to identify baseline factors associated with virological non-suppression between October 2020 and July 2022. A follow-up study was conducted in eastern Ethiopia among newly diagnosed people living with HIV (PLHIV). A questionnaire and a checklist were used to collect the data. Five milliliters of venous blood were obtained at baseline and six months to determine the VL. A VL test was performed using the Abbott RealTime HIV-1 assay. To determine predictors of virological non-suppression, bivariate and multivariate logistic regression analyses were used. There were 235 PLHIV enrolled, 70.6% of whom were female, with a mean age of 33.9 years. Of the 161 retained on ART, virological non-suppression was 8.7% at six months. Baseline predictors of virological non-suppression were age ≤ 30 years, a history of substance use, and a VL greater than 4-log10 copies/mL. In this cohort, virological non-suppression was found to be optimal but still lagged slightly behind the third 95%-target. Thus, targeted interventions, the introduction of baseline VL testing to improve treatment outcomes, and fostering the attainment of UNAIDS 95-95-95 targets are recommended. Furthermore, broader research is recommended to explore the reasons for virological non-suppression in the study area.

Evaluating the Frequencies of CNOT3, GRIA1, NFATC2, and PNPLA3 Variant Alleles and Their Association with L-Asparaginase Hypersensitivity in Pediatric Acute Lymphoblastic Leukemia in Addis Ababa, Ethiopia.

Introduction: L-asparaginase is a vital component for the treatment of childhood acute lymphoblastic leukemia (ALL); however, hypersensitivity reactions and hepatotoxicity hinder its anti-neoplastic efficacy. Previous reports indicated that genetic variants in CNOT3, GRIA1, and NFATC2 genes might be associated with hypersensitivity reactions and PNPLA3 with liver function. Objective: In this study, it was investigated whether this association also exists in a pediatric ALL cohort from Ethiopia. Methods: Three variants GRIA1 rs4958351, CNOT3 rs73062673, and NFATC2 rs6021191 were genotyped in a cohort of 160 patients. Association analysis to investigate the association with hypersensitivity reactions was performed using logistic regression analyses. Besides these variants, a variant in PNPLA3 (rs738409) was genotyped to assess the association with liver function. Results: Genotype frequencies of GRIA1 rs4958351, CNOT3 rs73062673, and NFATC2 rs6021191 were higher/lower than previously reported. One hundred and forty-four patients were included in the association analysis of which, 18 (12.5%) developed L-ASP hypersensitivity. Though the frequency of hypersensitivity was higher in patients that carried the risk alleles of the three investigated genes, no statistically significant differences were observed. Association analysis between PNPLA3 rs738409 and liver function could not be investigated due to a lack of clinical information. Conclusion: In conclusion, none of the tested genes did predict L-asparaginase hypersensitivity in an Ethiopian pediatric ALL patients.

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.

Frequency of viral infections in adolescent and adult in-patient Ethiopians with acute leukemia at presentation to a tertiary care teaching hospital: a cross-sectional study.

BACKGROUND: Leukemic patients are prone to infectious agents such as viruses due to dysregulated immune system resulting from infiltration of the bone marrow by malignant cells, chronic stimulation, reactivation of some viruses and viral pathogenicity as well as rarely from acquisition of a new infections leading to severe complications. However, the prevalence of these infections has not been systematically documented in resource-limited settings such as Ethiopia. OBJECTIVE: To determine the prevalence of HBV, HCV, and HIV among adult and adolescent in-patients with acute leukemia before the administration of chemotherapy, at the Tikur Anbessa Specialized Hospital (TASH) in Addis Ababa, Ethiopia. METHODS: A cross sectional study was conducted on 176 adult and adolescent inpatient Ethiopians, who were diagnosed with acute leukemia from April 2019 to June 2021. Socio-demographic characteristics and relevant clinical data were collected. Peripheral blood samples were collected and tested for HBV, HIV, and HCV using Enzyme-Linked Immunosorbent Assay (ELISA) and real-time PCR. Chi-square tests were used to assess associations between variables. RESULTS: Of the 176 patients, 109(62%) were males. The median age was 25[IQR,18-35] yr, with a range from 13 to 76 year. The prevalence of HBV (positivity for HBsAg plus HBV DNA), HCV and HIV was 21.6%, 1.7%, and 1.7%, respectively. HBsAg was positive in 19 cases (10.8%). Among 157 HBsAg negative patients, 52(33.1%) were positive for Anti-HBcAg; of these seropositive cases, 47.5% were positive for HBV DNA. Most DNA positive, HBsAg negative cases (79.0%) had DNA concentrations below 200 IU/ml indicating true occult HBV infection (OBI). Of the 176 cases, 122 had a history of blood transfusions, but no statistically significant association was found between HBV infection and blood product transfusion history (P = 0.963). CONCLUSIONS: The prevalence of HBV, HIV and HCV in patients with acute leukemia was similar to the national prevalence level of these infections. Given the HBsAg positivity and the high prevalence of occult hepatitis B infection in our study, these patients may be at increased risk for chemotherapy related hepatitis flares. Hence, clinicians caring these patients are strongly advised to screen their patients for HBV and also for HIV and HCV infections routinely.

Incidence and determinants of hematotoxicity in acute lymphoblastic leukemia children who received 6-mercaptopurine based maintenance therapy in Addis Ababa, Ethiopia.

INTRODUCTION: The maintenance phase of acute lymphoblastic leukemia treatment is the final and longest stage of treatment, mainly focused on antimetabolite therapy. This phase is essential to eliminate residual leukemic clones and prevent relapse. However, dose-limiting hematotoxicity is a major problem during this phase resulting in dose reduction or treatment discontinuation. OBJECTIVE: In this cohort study, the clinical features and risk factors of hematological toxicity during the maintenance phase of treatment were analyzed in pediatric patients from Ethiopia. METHODS: A total of 160 patients from Tikur Anbessa specialized hospital were included in the study of which 142 had sufficient data available for analysis. Patient characteristics as well as information about the care-givers, sides-effects as reported by the care-givers and clinical factors were collected. Bivariable followed by multivariable analysis was performed to investigate which factors were associated with hematological toxicity during the maintenance phase. RESULTS: During the first six months of maintenance phase treatment grade 4 neutropenia was detected in 52.8% of the patients. The risk of developing grade 4 neutropenia was increased by about two fold in children with the age of 6 years and less compared to those with the age of more than 6 years. Similarly, the rate of developing grade 4 neutropenia among children with less than 4,500 maintenance day 1 white blood cell counts was significantly higher than that of children with normal maintenance day 1 white blood cell counts (AHR 2.477, 95% CI = 1.461-4.200, p = 0.001). CONCLUSION: In conclusion, child's age and day 1 maintenance white blood cell/absolute neutrophil counts significantly affected the occurrence of grade 4 hematotoxicity. Close monitoring for white blood cell and absolute neutrophil counts during maintenance phase treatment is recommended for early diagnosis of hematotoxicity.

Clinicopathological Features of Invasive Breast Cancer: A Five-Year Retrospective Study in Southern and South-Western Ethiopia.

Background: Breast cancer (BC) is the most common type of cancer in Ethiopia. The incidence of BC is also rising, but the exact figure is still poorly known. Therefore, this study was conducted to address the gap in epidemiological data on BC in southern and southwestern Ethiopia. Materials and Methods: This is a five-year (2015-2019) retrospective study. The demographic and clinicopathological data were collected from biopsy reports of different kinds of breast carcinomas in the pathology department of Jimma University Specialized Hospital and Hawassa University Specialized Referral Hospital. Histopathological grades and stages were conducted using Nottingham grading and TNM staging system, respectively. Collected data were entered and analyzed using SPSS Version-20 software. Results: The mean age of patients at diagnosis was 42.27 (SD = 13.57) years. The pathological stage of most BC patients was stage III, and most of them had tumor sizes greater than 5 cm. Most patients had moderately differentiated tumor grade, and mastectomy was the most common type of surgery at the time of diagnosis. Invasive ductal carcinoma was the most common histological type of BC, followed by invasive lobular carcinoma. Lymph node involvement was seen in 60.5% of cases. Lymph node involvement was associated with tumor size (χ2 = 8.55, p = 0.033) and type of surgery (χ2 = 39.69, p < 0.001). Conclusions: This study showed that BC patients in southern and southwestern Ethiopia displayed advanced pathological stages, relatively young age at diagnosis, and predominant invasive ductal carcinoma histological patterns.

Genetic variants of genes involved in thiopurine metabolism pathway are associated with 6-mercaptopurine toxicity in pediatric acute lymphoblastic leukemia patients from Ethiopia.

Introduction: Genetic variation in the thiopurine S-methyltransferase (TPMT) gene by and large predicts variability in 6-mercaptopurine (6-MP) related toxicities. However, some individuals without genetic variants in TPMT still develop toxicity that necessitates 6-MP dose reduction or interruption. Genetic variants of other genes in the thiopurine pathway have been linked to 6-MP related toxicities previously. Objective: The aim of this study was to evaluate the effect of genetic variants in ITPA, TPMT, NUDT15, XDH, and ABCB1 on 6-MP related toxicities in patients with acute lymphoblastic leukemia (ALL) from Ethiopia. Methods: Genotyping of ITPA, and XDH was performed using KASP genotyping assay, while that of TPMT, NUDT15, and ABCB1 with TaqMan® SNP genotyping assays. Clinical profile of the patients was collected for the first 6 months of the maintenance phase treatment. The primary outcome was the incidence of grade 4 neutropenia. Bivariable followed by multivariable cox regression analysis was performed to identify genetic variants associated with the development of grade 4 neutropenia within the first 6 months of maintenance treatment. Results: In this study, genetic variants in XDH and ITPA were associated with 6-MP related grade 4 neutropenia and neutropenic fever, respectively. Multivariable analysis revealed that patients who are homozygous (CC) for XDH rs2281547 were 2.956 times (AHR 2.956, 95% CI = 1.494-5.849, p = 0.002) more likely to develop grade 4 neutropenia than those with the TT genotype. Conclusion: In conclusion, in this cohort, XDH rs2281547 was identified as a genetic risk factor for grade 4 hematologic toxicities in ALL patients treated with 6-MP. Genetic polymorphisms in enzymes other than TPMT involved in the 6-mercaptopurine pathway should be considered during its use to avoid hematological toxicity.

Diabetes mellitus is associated with an increased risk of unsuccessful treatment outcomes among drug-susceptible tuberculosis patients in Ethiopia: A prospective health facility-based study.

Background: The impact of diabetes mellitus on tuberculosis (TB) treatment outcomes has not been well investigated in most sub-Saharan countries including Ethiopia. The current study aimed to determine the association between diabetes mellitus and unsuccessful TB treatment outcomes among drug-susceptible TB patients treated at selected health facilities in Addis Ababa, Ethiopia. Methods: This health facility-based prospective cohort study was conducted at six randomly selected public health centers in Addis Ababa, from August 2020 until November 2021. Clinically diagnosed adult pulmonary and extra pulmonary TB patients were recruited at the time of treatment initiation. A multivariable logistic regression analysis was used to estimate the association between diabetes and unsuccessful TB treatment outcomes. Results: Among the total 267 enrolled participants, 9.7% of patients with TB were identified to have diabetes comorbidity. Of patients with diabetes and TB, 9 (34.6%) were newly diagnosed based on glucose test results. Despite an overall high TB treatment success rate (94.0%), more than one-fourth (26.9%) of patients with diabetes had a poor TB treatment outcome (26.9%), which was remarkably higher compared to patients without diabetes (3.7%). In multivariable regression, the adjusted odds of poor TB treatment outcome among those with diabetes was 14.8 (95% CI 3.5 - 62.7) times the odds of poor outcome patients without diabetes. Conclusion: Diabetes was significantly associated with increased odds of poor TB treatment outcomes among patients in Addis Ababa, Ethiopia.