LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems

Lymphocyte activation gene-3 (LAG-3) is a cell-surface molecule with diverse biologic effects on T cell function. We recently showed that LAG-3 signaling is important in CD4+ regulatory T cell suppression of autoimmune responses. Here, we demonstrate that LAG-3 maintains tolerance to self and tumor antigens via direct effects on CD8+ T cells using 2 murine systems. Naive CD8+ T cells express low levels of LAG-3, and expression increases upon antigen stimulation. Our data show increased levels of LAG-3 protein on antigen-specific CD8+ T cells within antigen-expressing organs or tumors. In vivo antibody blockade of LAG-3 or genetic ablation of the Lag-3 gene resulted in increased accumulation and effector function of antigen-specific CD8+ T cells within organs and tumors that express their cognate antigen. Most notably, combining LAG-3 blockade with specific antitumor vaccination resulted in a significant increase in activated CD8+ T cells in the tumor and disruption of the tumor parenchyma. A major component of this effect was CD4 independent and required LAG-3 expression by CD8+ T cells. Taken together, these data demonstrate a direct role for LAG-3 on CD8+ T cells and suggest that LAG-3 blockade may be a potential cancer treatment.     

Central nervous system toxoplasmosis in adult Ethiopians

OBJECTIVES: Toxoplasmosis is identified as one of the major central nervous system (CNS) opportunistic infections in AIDS patients. Sero-epidemiological surveys done among Ethiopian patients indicated a very high prevalence rate. This study was conducted to describe the clinical course of the disease in Ethiopians with AIDS. PATIENTS AND METHODS: Three hundred and twenty three patients with AIDS and CNS Toxoplasmosis that were consecutively admitted and treated with Sulfadoxine Pyrimethamine (SP) at the Tikur Anbessa Specialized Referral Hospital were reviewed. The diagnosis CNS Toxoplasmosis was made based on clinical features or neuroradiologic findings and response to treatment. In over 80% of the cases the dose of Pyrimethamine used was 100 mgs for two days and then 25 mgs daily PO. RESULTS: The male to female ratio was one to one. The median age was 34 years (range 18 - 75). The most common presenting symptoms were headache 293 (91%), fever 269 (83%), and abnormal level of consciousness in 201 (62%) of the cases. Focal neuralgic deficits were seen in 203 (63%) of the cases. The diagnosis of CNS toxoplasmosis was based on clinical features and response to treatment in 186 (58%) of the cases and on CT scan findings and clinical response in 54 (17%) of the cases. Among the 248 (78%) of the cases that had responded favorably to SP, 53% had improvement on the 7th day, while the rest had improvement on the 14th day of treatment. Major treatment related adverse reactions, which required changing treatment, were seen in 68 (20%) of the cases. Among patients who survived the first episode of toxoplasmosis, the median follow up was for 29 days (range 15-1800). CONCLUSION: Toxoplasmosis had been the most AIDS defining event in the study group and clinical response to empiric treatment was essentially diagnostic. In our study group the outcome seen with SP as compared to the standard recommended treatment yielded comparable results. Tolerance to treatment was better and the adverse effects warranting change in treatment were fewer despite that only few patients received folinic acid supplements. We recommend a well-designed prospective study to establish the efficacy and optimal dose of SP in the treatment of CNS toxoplasmosis.     

Effect of malaria infection on hematological profiles of people living with human immunodeficiency virus in Gambella,southwest Ethiopia

Background

Anemia is a strong predictor of mortality and poor quality of life among persons with either renal impairment or HIV infection. In this study, we investigated the prevalence of anemia and its association with renal insufficiency among HIV infected patients initiating ART at a hospital in Northeast Ethiopia.

Methods

In this retrospective cohort study, records of 373 patients on ART were selected in Dessie Referral hospital, South Wollo, Northeast Ethiopia from September 2010 to August 2013. Socio-demographic and clinical characteristics of the study patients were collected using standardized data extraction instrument. The abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) study equation was used to estimate renal function (GFR) from serum creatinine. SPSS version 20.0 statistical software was used for data analysis.

Results

The prevalence of anemia at the time of ART initiation was 34.4%; with 20.5, 12.3 and 1.6% mild, moderate and severe anemia, respectively. Renal insufficiency was present in 27.9% of patients and was associated with a high prevalence of anemia (74%). The prevalence of anemia increased with stage of insufficiency, from 23.7% in stage 1 to 100% in stage 4. Impaired renal function (eGFR < 60 mL/min/1.73 m²) was associated with a higher risk of all forms of anemia; i.e., mild (AOR = 3.96; 95% CI: 2.76–5.69), moderate (AOR = 2.21; 95% CI: 1.16–4.19) and severe anemia (AOR = 5.89; 95% CI: 1.02–12.03).

Conclusion

HIV infected patients with renal insufficiency had a higher prevalence of anemia compared to patients with normal renal function. Thus, screening of these patients for anemia and renal insufficiency at base line should be critical not only to reduce mortality but also to improve clinical outcomes.

     

National disability-adjusted life years (DALYs) for 257 diseases and injuries in Ethiopia, 1990–2015: findings from the global burden of disease study 2015

Background

Disability-adjusted life years (DALYs) provide a summary measure of health and can be a critical input to guide health systems, investments, and priority-setting in Ethiopia. We aimed to determine the leading causes of premature mortality and disability using DALYs and describe the relative burden of disease and injuries in Ethiopia.

Methods

We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for non-fatal disease burden, cause-specific mortality, and all-cause mortality to derive age-standardized DALYs by sex for Ethiopia for each year. We calculated DALYs by summing years of life lost due to premature mortality (YLLs) and years lived with disability (YLDs) for each age group and sex. Causes of death by age, sex, and year were measured mainly using Causes of Death Ensemble modeling. To estimate YLDs, a Bayesian meta-regression method was used. We reported DALY rates per 100,000 for communicable, maternal, neonatal, and nutritional (CMNN) disorders, non-communicable diseases, and injuries, with 95% uncertainty intervals (UI) for Ethiopia.

Results

Non-communicable diseases caused 23,118.1 (95% UI, 17,124.4–30,579.6), CMNN disorders resulted in 20,200.7 (95% UI, 16,532.2–24,917.9), and injuries caused 3781 (95% UI, 2642.9–5500.6) age-standardized DALYs per 100,000 in Ethiopia in 2015. Lower respiratory infections, diarrheal diseases, and tuberculosis were the top three leading causes of DALYs in 2015, accounting for 2998 (95% UI, 2173.7–4029), 2592.5 (95% UI, 1850.7–3495.1), and 2562.9 (95% UI, 1466.1–4220.7) DALYs per 100,000, respectively. Ischemic heart disease and cerebrovascular disease were the fourth and fifth leading causes of age-standardized DALYs, with rates of 2535.7 (95% UI, 1603.7–3843.2) and 2159.9 (95% UI, 1369.7–3216.3) per 100,000, respectively. The following causes showed a reduction of 60% or more over the last 25 years: lower respiratory infections, diarrheal diseases, tuberculosis, neonatal encephalopathy, preterm birth complications, meningitis, malaria, protein-energy malnutrition, iron-deficiency anemia, measles, war and legal intervention, and maternal hemorrhage.

Conclusions

Ethiopia has been successful in reducing age-standardized DALYs related to most communicable, maternal, neonatal, and nutritional deficiency diseases in the last 25 years, causing a major ranking shift to types of non-communicable disease. Lower respiratory infections, diarrheal disease, and tuberculosis continue to be leading causes of premature death, despite major declines in burden. Non-communicable diseases also showed reductions as premature mortality declined; however, disability outcomes for these causes did not show declines. Recently developed non-communicable disease strategies may need to be amended to focus on cardiovascular diseases, cancer, diabetes, and major depressive disorders. Increasing trends of disabilities due to neonatal encephalopathy, preterm birth complications, and neonatal disorders should be emphasized in the national newborn survival strategy. Generating quality data should be a priority through the development of new initiatives such as vital events registration, surveillance programs, and surveys to address gaps in data. Measuring disease burden at subnational regional state levels and identifying variations with urban and rural population health should be conducted to support health policy in Ethiopia.

     

Assessment of Knowledge and Attitude towards Palliative Care and Associated Factors among Nurses Working in North Wollo Hospitals

BackgroundPalliative care improves the quality of life of patients facing a life-threatening illness. Nurses should improve their caregiving capacity. In Ethiopia, palliative care is underestimated. The availability of data regarding the knowledge and attitude of nurses towards palliative care is critically important. Thus, this study aimed to assess the level of knowledge and attitude of nurses towards palliative care.MethodsInstitution-based, cross-sectional study was conducted in North Wollo hospitals. A simple random sampling technique was used. The data was collected using structured self-administered questionnaires from February to March 2019. The analysis was done using a binary logistic regression model. P-value < 0.05 was considered as statistically significant.ResultsThe result revealed that 59.7% of the respondents had good knowledge and 44.2% had a favorable attitude towards palliative care. Level of education, experience in caring for chronically ill patients, and experience in caring for dying family members within the last 6 months had a significant association with the knowledge of nurses. Monthly income, experience in caring for chronically ill patients, formal palliative care education, and knowledge were found statistically significant with the attitude of nurses towards palliative care.ConclusionMore than half of the nurses had good knowledge, but less than half of the respondents had a favorable attitude towards palliative care. Attention should be given towards palliative care by the health policy and needs to be incorporated into the national curriculum of nursing education.     

Preterm birth and its associated factors in Ethiopia: a systematic review and meta-analysis

BackgroundPreterm birth is a public health concern globally. In low- and middle-income countries, like Ethiopia, preterm birth is under reported and underestimated. Therefore, this systematic review and meta-analysis assessed the pooled prevalence and associated risk factors for preterm birth in Ethiopia.MethodsIn this review the databases used were PubMed, Google scholar, EMBASE, HINARI and African journal online. Publication bias was checked using a funnel plot and Eggers test.ResultsA total of 30 studies were included in this systematic review and meta-analysis. The overall pooled prevalence of preterm birth in Ethiopia was 11.4% (95% CI; 9.04, 13.76). On pooled analysis, preterm birth was associated with pregnancy-induced hypertension being HIV-positive, premature rupture of membrane, rural residence, the mother having a history of abortion, multiple pregnancies, and anemia during pregnancy.ConclusionThe national prevalence of preterm birth in Ethiopia was low. Early identifying those pregnant women who are at risk of the above determinants and proving quality healthcare and counsel them how to prevent preterm births, which decrease the rate of preterm birth and its consequences. So, both governmental and non-governmental health sectors work on the minimization of these risk factors.     

Ethical and scientific issues surrounding solid organ transplantation in HIV-positive patients: Absence of evidence is not evidence of absence.

End-stage liver disease is emerging as a leading cause of death among HIV-positive patients. Historically, an HIV diagnosis was a contraindication for a liver transplant; however, because of the efficacy of highly active antiretroviral therapy (HAART), HIV-positive patients have one-year, two-year, and three-year post-transplantation survival rates similar to that of HIV-negative patients. Based on this evidence, HIV-positive patients are now considered eligible for transplantation. However, newly emerging guidelines include the stipulation that HIV-positive patients must be on HAART to be placed on a waiting list for transplantation. The purpose of the present paper is to evaluate the scientific and ethical probity of requiring HIV-positive patients to be on HAART as a condition for being on a liver transplant waiting list. It is argued that the emphasis should be placed on the probability of post-transplantation HAART tolerance, and that concerns about pretransplantation HAART tolerance are of secondary importance.