Immune reconstitution inflammatory syndrome, a controversial burden in the East African context: a systematic review and meta-analysis.

Introduction: It is well established that starting antiretroviral therapy (ART) increases a patient's life expectancy among HIV-positive individuals. Considering the HIV pandemic, the major concern is initiation of ARTs to the large segment of HIV infected population, not adverse events from immune restoration. The prevalence of HIV-associated immune reconstitution inflammatory syndrome (IRIS) is poorly estimated due to Africa's underdeveloped infrastructure, particularly in Eastern Africa. Therefore, this study compiled data regarding the magnitude and associated factors of IRIS in the context of Eastern Africa. Methods: The electronic databases such as Google Scholar, PubMed, Web of Science, and free Google access were searched till 5 June 2021, and the search was lastly updated on 30 June 2022 for studies of interest. The pooled prevalence, and associated factors with a 95% confidence interval were estimated using the random effects model. The I2 and Egger's tests were used for heterogeneity and publication bias assessment, respectively. Results: The development of HIV-associated IRIS in Eastern Africa was estimated to be 18.18% (95% CI 13.30-23.06) in the current review. The two most common predictors of IRIS associated with Eastern Africa were the lower pre-ART CD4 T-cell count of 50 cells/µl and the low baseline body mass index level. Therefore, attention should be focused on the early detection and care of HIV-associated IRIS to reduce the morbidity and death caused by IRIS.

BCG-Induced Immune Training: Interplay between Trained Immunity and Emergency Granulopoiesis.

Bacille Calmette-Guérin (BCG) is the most commonly administered vaccine in human history. The medical application of BCG extends far beyond the fight against tuberculosis. Despite its stellar medical record over 100 years, insight into how BCG provides this vast range of benefits is largely limited, both for its pathogen-specific (tuberculosis) as well as pathogen-agnostic (other infections, autoimmunity, allergies, and cancer) effects. Trained immunity and emergency granulopoiesis have been identified as mediating BCG's pathogen-agnostic effects, for which some of the molecular mechanisms have been delineated. Upon review of the existing evidence, we postulate that emergency granulopoiesis and trained immunity are a continuum of the same effect cascade. In this context, we highlight that BCG's pathogen-agnostic benefits could be optimized by taking advantage of the age of the recipient and route of BCG administration.

Low level of HIV-1C integrase strand transfer inhibitor resistance mutations among recently diagnosed ART-naive Ethiopians.

With the widespread use of Integrase strand transfer inhibitors (INSTIs), surveillance of HIV-1 pretreatment drug resistance is critical in optimizing antiretroviral treatment efficacy. However, despite the introduction of these drugs, data concerning their resistance mutations (RMs) is still limited in Ethiopia. Thus, this study aimed to assess INSTI RMs and polymorphisms at the gene locus coding for Integrase (IN) among viral isolates from ART-naive HIV-1 infected Ethiopian population. This was a cross-sectional study involving isolation of HIV-1 from plasma of 49 newly diagnosed drug-naive HIV-1 infected individuals in Addis-Ababa during the period between June to December 2018. The IN region covering the first 263 codons of blood samples was amplified and sequenced using an in-house assay. INSTIs RMs were examined using calibrated population resistance tool version 8.0 from Stanford HIV drug resistance database while both REGA version 3 online HIV-1 subtyping tool and the jumping profile Hidden Markov Model from GOBICS were used to examine HIV-1 genetic diversity. Among the 49 study participants, 1 (1/49; 2%) harbored a major INSTIs RM (R263K). In addition, blood specimens from 14 (14/49; 28.5%) patients had accessory mutations. Among these, the M50I accessory mutation was observed in a highest frequency (13/49; 28.3%) followed by L74I (1/49; 2%), S119R (1/49; 2%), and S230N (1/49; 2%). Concerning HIV-1 subtype distribution, all the entire study subjects were detected to harbor HIV-1C strain as per the IN gene analysis. This study showed that the level of primary HIV-1 drug resistance to INSTIs is still low in Ethiopia reflecting the cumulative natural occurrence of these mutations in the absence of selective drug pressure and supports the use of INSTIs in the country. However, continues monitoring of drug resistance should be enhanced since the virus potentially develop resistance to this drug classes as time goes by.

Elevated KIR expression and diminished intensity of CD7 on NK cell subsets among treatment naïve HIV infected Ethiopians.

Natural killer (NK) cells are crucial effector cells of the innate immune response to viral infections, including HIV, through cytolytic activity and the production of cytokines with anti-HIV activities. We recruited 15 treatment naïve HIV patients and 16 healthy controls (HC) to assess NK cell subsets or expression of multiple markers by flow cytometry. The frequency of circulating CD56brightCD16-ve and CD56dimCD16bright NK cell subsets was significantly lower among the HIV group than in HC. The CD56-veCD16bright subset was higher in HIV patients, but this was only apparent when gated among total NK cells, not total lymphocytes. NK cells among HIV participants also showed a lower and higher frequency of CD8 and HLA-DR expressing cells, respectively. In addition, CD7 median fluorescent intensity and CD2+CD7- frequencies were significantly lower in HIV patients. A distinct population of KIR3DL1/S1 cells was unexpectedly higher among CD56brightCD16-ve NK cells in HIV patients. In conclusion, this study in the Ethiopian setting confirms many previous findings, but the down-regulation of CD7 and enhanced KIR3DL1/S1 within the CD56bright subsets have not been widely reported among HIV patients and merit further research.

Prevalence of HIV and Its Co-Infection with Hepatitis B/C Virus Among Chronic Liver Disease Patients in Ethiopia.

Background: The efficient use of antiretroviral drugs has significantly reduced AIDS-related morbidities and mortalities; however, mortality due to non-AIDS-related end-stage liver diseases is escalating in those living with HIV. Objective: The study was designed to determine the prevalence of HIV and its co-infection with HBV and HCV among chronic liver disease (CLD) patients in Ethiopia. Methods: Three hundred and forty-five CLD patients were included in this study in two groups: Hepatocellular carcinoma (HCC) (n=128) and non-HCC (n=217) patients. The non-HCC group comprised patients with advanced liver disease (n=98) and chronic hepatitis (n=119). Enzyme immunoassays were used to determine HBV and HCV infection markers. In addition, a serial rapid HIV testing algorithm was employed to screen HIV infection. Results: Regardless of the stage of liver disease, the overall frequency of HIV was 4.3% (15/345), with a 2% (7/345) and 0.3% (1/345) of HIV/HBV and HIV/HCV co-infection rate. Of all HIV-infected patients (n=15), 46.7% (7/15) and 6.7% (1/15) were co-infected with HBV (HBsAg+HBcAb+) and HCV (anti-HCV+ HCV-RNA+), respectively, and 86.7% (13/15) exhibited a marker of HBV exposure (total HBcAb+). Overall, the frequency of HIV and its co-infection with HBV was more noticeable among HCC than non-HCC patients [8.6% (11/128) vs 1.8 (4/217), p=0.005 and 3.9% (5/128) vs 0.9% (2/217), p=0.1]. The rate of HIV mono-infection was 3.9% (5/128) vs 0.9% (2/217) among HCC and non-HCC patients. Conclusion: The frequency of HIV and its co-infections with HBV/HCV exhibited an increasing pattern with the severity of the liver disease. Thus, screening all HIV-positive patients for HBV and HCV infection and all CLD patients for HIV infection and taking necessary preventive measures would be an essential strategy to prevent the progression of CLD and death related to liver disease in people living with HIV.

Targeting Metabolic Reprogramming of T-Cells for Enhanced Anti-Tumor Response.

Cancer immunotherapy is an effective treatment option against cancer. One of the approaches of cancer immunotherapy is the modification of T cell-based anti-tumor immune responses. T-cells, a type of adaptive immune response cells responsible for cell-mediated immunity, have long been recognized as key regulators of immune-mediated anti-tumor immunity. T-cell activities have been reported to be suppressed or enhanced by changes in cell metabolism. Moreover, metabolic reprogramming during activation of T cells is required for the development of distinct differentiation profiles of these cells, which may allow the development of long-term cell-mediated anti-tumor immunity. However, T cells have been shown to undergo metabolic exhaustion in tumor microenvironment (TME) as it poses several obstacles to their function. Applications of several mechanistic solutions to improve the efficacy of T cell-based therapies including chimeric antigen receptor (CAR) T cell therapy are yet to be determined. Modifying the metabolic properties of these cells and employing them in cancer immunotherapy is a potential strategy for improving their anti-tumor activity and therapeutic efficacy. To give an insight, in this review paper, we endeavoured to cover metabolic reprogramming in cancer and T cells, signalling mechanisms involved in immuno-metabolic regulation, the effects of the TME on T cell metabolic fitness, and targeting metabolic reprogramming of T cells for an enhanced anti-tumor response.

Evaluation of urine sample for diagnosis of visceral leishmaniasis using rK-39 immunochromatographic test in Northwest Ethiopia.

BACKGROUND: Visceral leishmaniasis is the most severe form of leishmaniasis which ranks second in mortality and fourth in morbidity. Parasitological diagnostic techniques with splenic aspirate remain the gold standard. However, sample collection is risky, painful, and difficult. Alternatively, serological techniques provide good diagnostic accuracy using serum sample that is difficult for applying on small children and in the field. So, finding alternative non-invasive and self-collected samples like urine is very important. Thus, the study aimed to evaluate the diagnostic performance of the rK-39 strip test using urine for diagnosis of visceral leishmaniasis. METHODS: A multicenter institutional-based cross-sectional study was conducted from November 2019 to March 2021 at Northwest Ethiopia. Sociodemographic information was collected using a structured questionnaire. Blood sample and midstream urine sample were collected for rK-39 test. Data were entered into Epi-data version 4.2 and analyzed using SPSS version 24.0. Diagnostic performance parameters of urine-based rK-39 rapid test, i.e. sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios (LR+/-), and diagnostic accuracy were determined on contingency table by using serum-based rK-39 test result as a reference. An agreement between urine and serum-based rK-39 test was statistically determined by kappa value. RESULT: In total, 300 subjects, age ranged between 7 and 60 years, were included in the study. The overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of urine-based rK-39 test were found to be 98.0% (95% CI: 93.0% - 99.8%), 95.5% (95% CI: 91.6% - 97.9%), 91.6% (95% CI: 85.2%- 95.4%), 98.9 (95% CI: 96.0%- 99.7%), and 96.33% (95% CI: 93.53-98.16%), respectively. Additionally, there was a strong agreement between the results obtained on rK-39 ICT using urine and serum samples (kappa = 0.92; P < 0.001). CONCLUSION: Urine-based rK-39 ICT had an excellent high sensitivity, specificity and strong agreement with serum-based rK-39 ICT results. This indicates that urine sample would be a promising noninvasive and easy to collect sample for diagnosis of VL in field and rural settings.

Risk factors for Brucellosis and knowledge-attitude practice among pastoralists in Afar and Somali regions of Ethiopia.

BACKGROUND: Brucellosis is a neglected bacterial zoonotic disease with substantial economic impact on households. Pastoral communities are a potential risk group due to their way of life being closely interlinked with their large livestock herds. METHODOLOGY: A semi-structured questionnaire survey was conducted in households in the pastoral Afar and Somali (SRS) regions. All households had people and animals serologically tested for brucellosis. Questions were related to husbandry, consumption habits, and knowledge-attitude-practice towards the disease and zoonoses. Descriptive statistics and logistic analysis were performed to assess potential risk factors for having households with positive humans and/or animals. RESULT: 647 households were included in the survey. Herd brucellosis prevalence was 40.3 % (15.9-86.3 % in Afar; 4-72.2 % in SRS). Over half (56.3 %) of the households in Afar and 41.8 % in SRS had at least one human reactor. Nearly a quarter of the households (22.8 %), recalled abortions in goats in the last 12 months, whereas 52.5 % and 50.3 % recalled stillborn in all species and membrane retentions respectively. All respondents drank raw milk and discarded animal afterbirths in the direct surroundings with minimal protection. Risk factors for animal reactors were goat herd size, and goat abortion. There was no identified risk factor for having human reactors in households. None of the households knew about brucellosis. CONCLUSION: Although being endemic in Afar and SRS, Brucellosis is not known by the pastoralists. Brucellosis control programs will have to be tailored to the pastoral context, accounting for their mobility, large, multi-species herds and habits.

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.

Diabetes mellitus among adults on highly active anti-retroviral therapy and its associated factors in Ethiopia: Systematic review and meta-analysis.

BACKGROUND: Diabetes mellitus occurs as a comorbid illness among people living with HIV and, in particular those on Highly Active Anti-retroviral therapies (HAART). Previous studies have documented the prevalence of diabetes mellitus among adults on HAART; however, there is lack of comprehensive estimation. Hence, this study was aimed to estimate the pooled prevalence and associated factors of diabetes mellitus among adults on HAART in Ethiopia. METHODS: Primary studies were exhaustively searched using Cochrane, PubMed, Google Scholar, Scopus and Web of science databases until February 2021. Eligible studies were selected and critically appraised for quality using the Joanna Briggs Institute (JBI) quality appraisal checklist. The required data were extracted and exported to Stata version 16 for meta-analysis. The overall prevalence of diabetes mellitus among adults on HAART was estimated using a weighted inverse random effect model. Sensitivity and sub-group analysis were conducted for evidence of heterogeneity. Trim and fill analysis was performed after Egger's test and funnel plot were indicating the presence of publication bias. RESULTS: A total of 17 studies with 6,052 subjects on HAART were included. The pooled prevalence of diabetes mellitus among patients on HAART was 16.04% [95% Confidence Interval (CI); 11.6, 20.92]. Abnormal High Density Lipoprotein Cholesterol (HDL-C) [Adjusted Odd Ratio (AOR) = 4.68, 95% CI; 2.54, 6.82], Body Mass Index (BMI) ≥ 25 kg/m2 [AOR = 7.41, 95% CI; 2.75, 12.08], ≥6 years ART [AOR = 8.14, 95% CI; 5.85, 30.43], hypertension [AOR = 3.29, 95% CI; 2.13, 4.45], age 35-44 years [AOR = 6.28; 95% CI; 4.20, 8.37, BMI ≥ 30 kg/m2 [AOR = 7.81, 95% CI; 4.97, 10.64], educational status above diploma [AOR = 6.42, 95% CI; 1.28, 11.57] and age 45-55 years [AOR = 4.46, 95% CI; 2.81, 6.10] were positively associated with diabetes mellitus comorbidity among adults on HAART. CONCLUSION: The higher prevalence of diabetes mellitus was observed for adults on HAART. HDL-C, duration of ART, hypertension, overweight, obesity, age and educational status of participants increases the prevalence of diabetes mellitus. The study highlights the importance of timely screening of HDL-C level, blood pressure and BMI for adults on HAART.

Macrosomia and its predictors in pregnant women with diabetes in Ethiopia.

BACKGROUND: To estimate the prevalence of macrosomia and contributing factors among pregnant women with diabetes in Ethiopia. METHODS: The Cochrane, PubMed, Google Scholar, SCOPUS, Web of Science electronic databases and grey literature found in online university repositories were searched for primary studies reporting the prevalence of macrosomia (birth weight ≥4 kg, irrespective of gestational age) and/or at least one determinant factor using WHO diabetes diagnosis criteria were involved. Variations across the studies were checked using the I2  statistic; funnel plot and Egger's test were used to assess publication bias. A weighted inverse random effect model was used to estimate the overall prevalence of macrosomia. RESULTS: The overall prevalence of macrosomic newborns among pregnant women with diabetes [15.1% (95% CI: 9.0%, 21.2%)] was higher than the prevalence among non-diabetic mothers (3.9%). Maternal blood glucose level >100 mg/dl [AOR = 10.5: 95% CI: 5.9, 15.1] and >120 mg/dl [AOR = 8.8: 95% CI: 4.5, 13.0], lack of Antenatal Care (ANC) visit [AOR = 10.8: 95% CI: 6.0, 15.0], previous adverse birth outcomes and advanced maternal age [AOR = 3.5: 95% CI: 1.0, 5.9] were significantly associated with the prevalence of macrosomia at 95% CI. CONCLUSION: The pooled prevalence of macrosomia among pregnant women with diabetes was higher than the prevalence among non-diabetic pregnant women (3.9%). Advanced maternal age, previous adverse birth outcomes, lack of ANC and uncontrolled maternal plasma glucose level were independent predictors of macrosomia.

Integrated human-animal sero-surveillance of Brucellosis in the pastoral Afar and Somali regions of Ethiopia.

BACKGROUND: Brucellosis is widespread in Ethiopia with variable reported prevalence depending on the geographical area, husbandry practices and animal species. However, there is limited information on the disease prevalence amongst pastoral communities, whose life is intricately linked with their livestock. METHODOLOGY: We conducted an integrated human-animal brucellosis sero-surveillance study in two adjacent pastoral regions, Afar and Somali region (SRS). This cross-sectional study included 13 woredas (districts) and 650 households. Blood samples were collected from people and livestock species (cattle, camel, goats and sheep). Sera were analyzed with C-ELISA for camels and shoats (sheep and goats), with I-ELISA for cattle and IgG ELISA for humans. Descriptive and inferential statistics analyses were performed. RESULTS: A total of 5469 sera were tested by ELISA. Prevalence of livestock was 9.0% in Afar and 8.6% in SRS (ranging from 0.6 to 20.2% at woreda level). In humans, prevalence was 48.3% in Afar and 34.9% in SRS (ranging from 0.0 to 74.5% at woreda level). 68.4% of all households in Afar and 57.5% of households in SRS had at least one animal reactor. Overall, 4.1% of animals had a history of abortion. The proportion of animals with abortion history was higher in seropositive animals than in seronegative animals. Risk factor analysis showed that female animals were significantly at higher risk of being reactors (p = 0.013). Among the species, cattle had the least risk of being reactors (p = 0.014). In humans, there was a clear regional association of disease prevalence (p = 0.002). The older the people, the highest the odds of being seropositive. CONCLUSION: Brucellosis is widespread in humans and animals in pastoral communities of Afar and SRS with the existence of geographical hotspots. No clear association was seen between human and particular livestock species prevalence, hence there was no indication as whether B. abortus or B. melitensis are circulating in these areas, which warrants further molecular research prior to embarking on a national control programs. Such programs will need to be tailored to the pastoral context.

Coagulopathy in SARS-CoV-2 Infected Patients: Implication for the Management of COVID-19.

COVID-19 disease has led to an extraordinary inclusive health crisis globally. Elevation of D-dimer is the major remarkable abnormal coagulation test in seriously ill COVID-19 patients. In nearly 50% of COVID-19 patients, the value of D-dimer was significantly enhancing. Recent literature indicated that COVID-19 patients were at higher risk of developing disseminated intravascular coagulation. Pro-inflammatory cytokines and chemokines are some of the factors leading to these conditions. The majority of COVID-19 patients showed a higher profile of pro-inflammatory cytokines and chemokines in severe clinical conditions. Tumor necrosis factor-α (TNF-α) and interleukins (ILs) elevated in COVID-19 infected patients. TNF-α, IL-6, and IL-1 are major cytokines vital for the inhibition of intrinsic anticoagulant pathways. COVID-19 becomes a higher complication with a significant effect on blood cell production and hemostasis cascades. Deep vein thrombosis and arterial thrombosis are common complications. Changes in hematological parameters are also frequently observed in COVID-19 patients. Especially, thrombocytopenia is an indicator for poor prognosis of the disease and is highly expected and aggravates the likelihood of death of SARS-CoV-2 infected individuals. Thrombopoiesis reduction in COVID-19 patients might be due to viral abuse of the bone marrow/the viral load may affect thrombopoietin production and function. In other ways, immune-inflammation-mediated destruction and increased consumption of platelets are also the possible proposed mechanisms for thrombocytopenia. Therefore, the counting of platelet cells is an easily accessible biomarker for disease monitoring. All SARS-CoV-2 infected patients should be admitted and identifying potential higher-risk patients. It is also obligatory to provide appropriate treatments with intensive care and strict follow-up. In addition, considerations of chronic diseases are essential for better prognosis and recovery. The current review discusses coagulopathy among SARS-CoV-2 infected individuals and its complication for the management of the disease.

Prevalence and Determinants of Pre-Cancerous Cervical Lesion and Human Papillomavirus Among HIV-Infected and HIV-Uninfected Women in North-West Ethiopia: A Comparative Retrospective Cross-Sectional Study.

BACKGROUND: The poor socio-economic status, underdeveloped health care system, and the high HIV/AIDS burden have potentially increased the incidence of cervical cancer in sub-Saharan Africa (SSA) including Ethiopia. Studies on the magnitude of pre-cancerous cervical lesion and human papillomavirus (HPV) among HIV-infected women are still limited, particularly in the current study setting. Thus, we determined the prevalence of pre-cancerous cervical lesion and HPV among HIV-infected women in comparison with HIV-uninfected women at Debre Tabor Comprehensive Specialized Hospital (DTCSH), North-West Ethiopia. METHODS: Hospital-based comparative retrospective cross-sectional study was conducted among 546 women from July 2018 to January 2020 at DTCSH. All records during the study period were collected using a structured checklist. Epi data version 4.02 and SPSS version 25.0 were used for data entry and analysis, respectively. RESULTS: The overall prevalence of pre-cancerous cervical lesion among 546 women was 8.8%. The prevalence of pre-cancerous cervical lesion was comparable between HIV-infected (9.3%) and HIV-uninfected women (8.6%) (p = 0.859). Age >45 years old, widowed marital status, multiparous (women ≥ 5 childbirths), and educational status were independent contributing factors of a pre-cancerous cervical lesion. Regarding HPV prevalence, among 109 screened women, 7 (6.4%) were positive for both HPV 16 and 18 strains. CONCLUSION: HIV infection was not statistically correlated with the magnitude of pre-cancerous cervical lesion (p = 0.859). Women in the study setting developed pre-cancerous cervical lesions irrespective of their HIV status. Hence, we recommend routine screening of women for pre-cancerous cervical lesion and HPV infection regardless of their HIV status for early management and prevention of associated morbidity and/or mortality.

Association of IL-10 (- 1082 A/G) and IL-6 (- 174 G/C) gene polymorphism with type 2 diabetes mellitus in Ethiopia population.

BACKGROUND: Interleukin (IL)-6 and IL-10 are the most important cytokine with pro and anti-inflammatory activities, respectively. Dysregulation of IL-6 and IL-10 are associated with increased risk of developing Type 2 Diabetes Mellitus (T2DM). Despite this, a fundamental understanding of both cytokine gene polymorphisms with its expression is critical in understanding of cellular mechanism of insulin resistance as well as T2DM intervention. Therefore, this study aimed to assess IL-6 (- 174 G/C) and IL-10 (- 1082 A/G) gene polymorphism, and its association with T2DM, North West Ethiopia. METHODS: A comparative cross-sectional study from January to May 2018 was conducted on study participants with T2DM and apparently healthy controls. Deoxyribonucleic acid (DNA) extraction and genotyping was carried out by using amplification refractory mutation system polymerase chain reaction to detect polymorphism of IL-6 and IL-10 gene at the position - 174 and - 1082, respectively. The logistic regression model was fitted to assess the association of between cytokine gene polymorphisms and T2DM. Odds ratio with 95% CI was determined to assess the presence and strength of association between the explanatory variables and outcome variable. A P-value < 0.05 was considered as statistically significant. RESULT: Participants carrying the GG genotype of IL-6 (- 174) (OR (95% CI) = 4.61 (2.07-10.54) was a high likelihood of having T2DM compared to those carrying the CC and AA genotypes. AA and AG genotypes of IL-10 (- 1082) were at lower odd of developing T2DM compared to those carrying the GG genotype. In addition, individuals carrying the G allele of IL-6 (- 174) have 2.82-fold odds of developing T2DM compared to individuals carrying the C allele (OR (95% CI) =2.81 (1.78-4.50)). CONCLUSION: Our study revealed that genetic polymorphisms of IL-6 (- 174) GG genotype is the potential host genetic risk factors to T2DM. While, IL-10 (- 1082) AA genotype is negatively associated with T2DM. Therefore, IL-6 (- 174) and IL-10 (- 1082) genetic variation may be considered as a biomarker for early screening and diagnosis of T2DM.

Correction: Adverse birth outcome and associated factors among diabetic pregnant women in Ethiopia: Systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0241811.].

Viral Etiologies of Meningitis in Patients with Presumed Pyogenic Meningitis at University Hospitals in Ethiopia.

INTRODUCTION: Viral meningitis is common in most resource-limited settings, posing a challenge for the management and prognosis of suspected patients. No study has been done on the detection of either viral or viral-bacterial co-infection among presumed pyogenic meningitis cases in Ethiopia. We, therefore, aimed to determine the distribution of cytomegalovirus (CMV) and human enteroviruses (HEVs) among patients with presumptive pyogenic meningitis at University hospitals in Ethiopia. METHODS: Viral nucleic acid was extracted from 86 repository CSF samples, which were collected from patients presumptively diagnosed with pyogenic meningitis between 2012 and 2013. PCR was done consecutively to investigate the possible viral etiologic agents of meningitis. RESULTS: HEVs were detected in 11 (12.8%) of the analyzed samples while none of the 86 samples were tested positive for CMV. Viral-bacterial co-infections were found among 4/11 (36.4%) confirmed cases. The majority of the patients (10/11) with HEVs were younger aged ≤ 19 years old. CONCLUSIONS: In this study, the magnitude of HEVs was shown to have a significant role in presumed pyogenic meningitis cases. Therefore, we recommend presumed pyogenic meningitis cases to be inspected for viral etiologies and improve meningeal symptoms interpretations.

Human cytomegalovirus infection among treatment-naive HIV-1 infected patients in Ethiopia.

Subclinical human cytomegalovirus (HCMV) replication is associated with immune dysfunction in immuno-suppressed antiretroviral therapy (ART) naive HIV infected individuals. No data is documented in Ethiopia so far concerning HCMV co-infection among HIV infected individuals. Hence, this study was aimed at generating data regarding the prevalence of active HCMV infection among treatment-naive HIV-infected individuals from Ethiopia. For this purpose, we enrolled 97 treatment-naive HIV infected study subjects in Addis Ababa from June to December 2018. ELISA and conventional PCR were performed consecutively to detect HCMV specific IgM antibody and HCMV DNA respectively. Of the 97 study subjects, 12 (12.4%) were positive for anti-CMV IgM antibodies but were not confirmed by PCR. With regard to the PCR positivity, 4/97 (4.1%) samples were positive for HCMV DNA. No statically significant associations were found between the dependent and independent variables. The presence of HCMV DNA in the current study highlights the need for a routine laboratory diagnosis for preventing HCMV disease among HIV-infected individuals early. Besides, the use of anti-CMV therapy for these CMV viremic individuals is also recommended as this can reduce the burden of CMV complications and consecutively prolonging the life of HIV infected individuals.

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.

Enhanced identification of Group B streptococcus in infants with suspected meningitis in Ethiopia.

Meningitis is one of the top ten causes of death among Ethiopian infants. Group B streptococcus (GBS) has emerged as a leading cause of meningitis in neonates and young infants, resulting in high mortality. Despite this, there is no report on GBS associated meningitis in Ethiopia where infant meningitis is common. Hence, the aim of this study was to determine the proportion of GBS associated meningitis among Ethiopian infants. PCR was prospectively used to detect GBS in culture-negative cerebrospinal fluid (CSF) samples, which were collected from infants suspected for meningitis, at Tikur Anbessa specialized hospital, Ethiopia, over a one-year period. GBS was detected by PCR in 63.9% of culture-negative CSF samples. Out of the 46 GBS positive infants, 10.9% (n = 5) of them died. The late onset of GBS (LOGBS) disease was noted to have a poor outcome with 3 LOGBS out of 5 GBS positive samples collected from patients with the final outcome of death. PCR was advantageous in the identification of GBS in culture-negative CSF samples. GBS was detected in 64% of the CSF samples from infants with meningitis compared with zero-detection rate by culture.