5 research outputs found

    Polymorphisms in CARD8 and NLRP3 are associated with extrapulmonary TB and poor clinical outcome in active TB in Ethiopia

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    Innate immunity is a first line defense against Mycobacterium tuberculosis infection where inflammasome activation and secretion of the pro-inflammatory cytokine IL-1beta, plays a major role. Thus, genetic polymorphisms in innate immunity-related genes such as CARD8 and NLRP3 may contribute to the understanding of why most exposed individuals do not develop infection. Our aim was to investigate the association between polymorphisms in CARD8 and NLRP3 and active tuberculosis (TB) as well as their relationship to treatment outcome in a high-endemic setting for TB. Polymorphisms in CARD8 (C10X) and NLRP3 (Q705K) were analysed in 1190 TB patients and 1990 healthy donors (HD). There was a significant association between homozygotes in the CARD8 polymorphism and extrapulmonary TB (EPTB), which was not the case for pulmonary TB or HDs. Among TB-patients, there was an association between poor treatment outcome and the NLRP3 (Q705K) polymorphism. Our study shows that inflammasome polymorphisms are associated with EPTB and poor clinical outcome in active TB in Ethiopia. The practical implications and determining causal relationships on a mechanistic level needs further study.Funding Agencies|Research Council of South East of Sweden (FORSS); Swedish International Development Cooperation Agency (SIDA); Heart and Lung Foundation; Swedish Research Council</p

    MOLECULAR CHARACTERIZATION OF HUMAN PAPILLOMA VIRUS FROM CERVICAL PRECANCEROUS AND CANCER SPECIMENS AMONG ETHIOPIAN AND SUDANESE WOMEN

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    Cancer of the uterine cervix continues to be a serious public health threat of global importance; 273,500 women are estimated to be dying from it annually. According to WHO reports, the age adjusted incidence rate of cervical cancer in Ethiopia and Sudan are 35.5 and 19.02 per 100,000 population respectively. Molecular and epidemiological studies have shown that Human Papilloma virus (HPV) is considered as the etiological agent for cervical cancer. Designing an effective vaccine against oncogenic HPV genotypes could have immense impact on the global cervical cancer burden. It was shown that a person protected against a specific type of HPV would still be at risk of getting infected with other cancer-inducing HPV genotypes. This necessitates that individuals living in different geographical localities receive vaccines based on the specific genotypes prevalent in that particular area. A retrospective molecular analysis for Human Papilloma virus was done on 245 formalin fixed paraffin embedded cervical biopsy samples bearing different histopathologic abnormalities that were collected from Ethiopia and the Sudan (160 and 85 samples respectively). The median age of the women who had given the biopsy samples were 45 and 48 (Range: 21-85; 30-75) for samples collected from Ethiopia and the Sudan respectively. DNA was extracted using phenol-chloroform extraction method and PCR was done to amplify the house keeping gene, β-globin, with PCO4, GH20 primers. Institutional ethical clearance was obtained from AHRI/ALERT, Addis Ababa University and Institute of Endemic Diseases ethical review committees. Amplification of HPV and subsequent genotyping was done on samples that were positive for the housekeeping gene using SPF10 primers and Line Probe Assay (LiPA) respectively. Accordingly, 93% (149/160) and 94% (80/85) of samples collected from Ethiopia and Sudan respectively were positive for HPV DNA. High risk (HR-HPV) and Low risk (LR-HPV) HPV genotypes were identified from 93% (149/160) and 13% (21/160) of all samples collected from Ethiopia respectively. Among the samples collected from Sudan, 94% (80/85) harbored high risk and 11.7% (10/85) low risk HPV v genotypes. Low risk HPV genotypes were detected as part of a mixed infection with at least one other HR-HPV type in both groups. HPV 16 was found to be the most frequent HPV genotype in Ethiopia and the Sudan accounting for 91% (136/149) and 82.5 % (66/80) respectively. Next to HPV 16, HPV 52, 58 and 18 were the second, third and fourth common HPV genotypes identified in Ethiopia. On the other hand, HPV 18, 45 and 52 were the second, third and fourth HPV genotypes identified in samples collected from Sudan. Mixed infections mainly composed of HPV 16, 18, 31, 33, 35, 45, 52, 58, and 68 were observed from samples collected from the two countries. Multiple infection with more than one HPV genotypes were identified in 59% (88/149) samples positive for HPV genotypes from Ethiopia and among 49% (39/80) HPV positive samples from the Sudan. The trend of having multiple genotypes reached to its highest peak in the age group 41- 60 and declined after the age 60 in samples collected from the two countries. It is recommended that a wide population-based epidemiological study be conducted to define the exact picture of this disease. A suitable vaccine targeting mainly HPV 16, 18, 45, 52 and 58 will have substantial impact on cervical cancer control in the two countries

    Progress in health among regions of Ethiopia, 1990-2019: a subnational country analysis for the Global Burden of Disease Study 2019.

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    BACKGROUND: Previous Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) studies have reported national health estimates for Ethiopia. Substantial regional variations in socioeconomic status, population, demography, and access to health care within Ethiopia require comparable estimates at the subnational level. The GBD 2019 Ethiopia subnational analysis aimed to measure the progress and disparities in health across nine regions and two chartered cities. METHODS: We gathered 1057 distinct data sources for Ethiopia and all regions and cities that included census, demographic surveillance, household surveys, disease registry, health service use, disease notifications, and other data for this analysis. Using all available data sources, we estimated the Socio-demographic Index (SDI), total fertility rate (TFR), life expectancy, years of life lost, years lived with disability, disability-adjusted life-years, and risk-factor-attributable health loss with 95% uncertainty intervals (UIs) for Ethiopia's nine regions and two chartered cities from 1990 to 2019. Spatiotemporal Gaussian process regression, cause of death ensemble model, Bayesian meta-regression tool, DisMod-MR 2.1, and other models were used to generate fertility, mortality, cause of death, and disability rates. The risk factor attribution estimations followed the general framework established for comparative risk assessment. FINDINGS: The SDI steadily improved in all regions and cities from 1990 to 2019, yet the disparity between the highest and lowest SDI increased by 54% during that period. The TFR declined from 6·91 (95% UI 6·59-7·20) in 1990 to 4·43 (4·01-4·92) in 2019, but the magnitude of decline also varied substantially among regions and cities. In 2019, TFR ranged from 6·41 (5·96-6·86) in Somali to 1·50 (1·26-1·80) in Addis Ababa. Life expectancy improved in Ethiopia by 21·93 years (21·79-22·07), from 46·91 years (45·71-48·11) in 1990 to 68·84 years (67·51-70·18) in 2019. Addis Ababa had the highest life expectancy at 70·86 years (68·91-72·65) in 2019; Afar and Benishangul-Gumuz had the lowest at 63·74 years (61·53-66·01) for Afar and 64.28 (61.99-66.63) for Benishangul-Gumuz. The overall increases in life expectancy were driven by declines in under-5 mortality and mortality from common infectious diseases, nutritional deficiency, and war and conflict. In 2019, the age-standardised all-cause death rate was the highest in Afar at 1353·38 per 100 000 population (1195·69-1526·19). The leading causes of premature mortality for all sexes in Ethiopia in 2019 were neonatal disorders, diarrhoeal diseases, lower respiratory infections, tuberculosis, stroke, HIV/AIDS, ischaemic heart disease, cirrhosis, congenital defects, and diabetes. With high SDIs and life expectancy for all sexes, Addis Ababa, Dire Dawa, and Harari had low rates of premature mortality from the five leading causes, whereas regions with low SDIs and life expectancy for all sexes (Afar and Somali) had high rates of premature mortality from the leading causes. In 2019, child and maternal malnutrition; unsafe water, sanitation, and handwashing; air pollution; high systolic blood pressure; alcohol use; and high fasting plasma glucose were the leading risk factors for health loss across regions and cities. INTERPRETATION: There were substantial improvements in health over the past three decades across regions and chartered cities in Ethiopia. However, the progress, measured in SDI, life expectancy, TFR, premature mortality, disability, and risk factors, was not uniform. Federal and regional health policy makers should match strategies, resources, and interventions to disease burden and risk factors across regions and cities to achieve national and regional plans, Sustainable Development Goals, and universal health coverage targets. FUNDING: Bill & Melinda Gates Foundation

    Progress in health among regions of Ethiopia, 1990-2019 : a subnational country analysis for the Global Burden of Disease Study 2019

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