Armauer Hansen Research Institute

Addis Ababa, Ethiopia

Armauer Hansen Research Institute

Addis Ababa, Ethiopia
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Ayele F.T.,Human Genome Research Institutes | Ayele F.T.,Armauer Hansen Research Institute | Adeyemo A.,Human Genome Research Institutes | Finan C.,Brighton and Sussex Medical School | And 7 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: Podoconiosis is a tropical lymphedema resulting from long-term barefoot exposure to red-clay soil derived from volcanic rock. The World Health Organization recently designated it as a neglected tropical disease. Podoconiosis develops in only a subgroup of exposed people, and studies have shown familial clustering with high heritability (63%). METHODS: We conducted a genomewide association study of 194 case patients and 203 controls from southern Ethiopia. Findings were validated by means of family-based association testing in 202 family trios and HLA typing in 94 case patients and 94 controls. RESULTS: We found a genomewide significant association of podoconiosis with the singlenucleotide polymorphism (SNP) rs17612858, located 5.8 kb from the HLA-DQA1 locus (in the allelic model: odds ratio, 2.44; 95% confidence interval [CI], 1.82 to 3.26; P = 1.42×10 -9; and in the additive model: odds ratio, 2.19; 95% CI, 1.66 to 2.90; P = 3.44×10 -8), and suggestive associations (P<1.0×10 -5) with seven other SNPs in or near HLA-DQB1, HLA-DQA1, and HLA-DRB1. We confirmed these associations using family-based association testing. HLA typing showed the alleles HLA-DRB1*0701 (odds ratio, 2.00), DQA1*0201 (odds ratio, 1.91), and DQB1*0202 (odds ratio, 1.79) and the HLA-DRB1*0701-DQB1*0202 haplotype (odds ratio, 1.92) were risk variants for podoconiosis. CONCLUSIONS: Association between variants in HLA class II loci with podoconiosis (a noncommunicable disease) suggests that the condition may be a T-cell-mediated inflammatory disease and is a model for gene-environment interactions that may be relevant to other complex genetic disorders. (Funded by the Wellcome Trust and others.) Copyright © 2012 Massachusetts Medical Society.


Tadesse T.,University of Gondar | Demissie M.,Addis Continental Institute of Public Health | Berhane Y.,Addis Continental Institute of Public Health | Kebede Y.,University of Gondar | Abebe M.,Armauer Hansen Research Institute
BMC Public Health | Year: 2013

Background: Timely tuberculosis treatment initiation and compliance are the two key factors for a successful tuberculosis control program. However, studies to understand patents' perspective on tuberculosis treatment initiation and compliance have been limited in Ethiopia. The aim of this study is to attempt to do that in rural Ethiopia. Methods. This qualitative, phenomenological study conducted 26 in-depth interviews with tuberculosis patients. A thematic content analysis of the interviews was performed using the Open Code software version 3.1. Results: We found that lack of geographic access to health facilities, financial burdens, use of traditional healing systems and delay in diagnosis by health care providers were the main reasons for not initiating tuberculosis treatment timely. Lack of geographic access to health facilities, financial burdens, quality of health services provided and social support were also identified as the main reasons for failing to fully comply with tuberculosis treatments. Conclusions: This study highlighted complexities surrounding tuberculosis control efforts in Dabat District. Challenges of geographic access to health care facilities and financial burdens were factors that most influenced timely tuberculosis treatment initiation and compliance. Decentralization of tuberculosis diagnosis and treatment services to peripheral health facilities, including health posts is of vital importance to make progress toward achieving tuberculosis control targets in Ethiopia. © 2013 Tadesse et al.; licensee BioMed Central Ltd.


Tadesse T.,University of Gondar | Demissie M.,Addis Continental Institute of Public Health | Berhane Y.,Addis Continental Institute of Public Health | Kebede Y.,University of Gondar | Abebe M.,Armauer Hansen Research Institute
PLoS ONE | Year: 2011

Background: Tuberculosis (TB) case detection rate remains low in Ethiopia. One of the underlying reasons is the emphasis on passive case finding strategy which may seriously underestimate the burden of the disease. Estimating the prevalence of smear-positive pulmonary TB through active case finding at population level can help assessing the degree to which passive case detection is successful. Methods and findings: This is population based cross-sectional study. The study population was all individuals aged ≥14 years. Interviews using a uniform questionnaire were done initially to identify individuals with chronic cough (≥15 days) and the two sputum (spot and morning) samples were gathered for standard smear microscopy. A total of 23,590 individuals aged ≥14 years were interviewed and 984 had a chronic cough for ≥15 days. Of 831 individuals who provided two sputum samples for acid fast bacilli (AFB), 41 had positive smears. A total of 22 smear-positive TB cases detected through passive case finding were on anti-TB treatment. The prevalence of new smear-positive TB was 174 per 100,000 in persons aged ≥14 years (95% CI: 121-227).The ratio of active to passive case finding was 2:1. Higher rates of smear-positivity were observed among females [AOR: 3.28, 95% CI (1.54-6.77)], and in the age group ≥45 years [AOR: 2.26, 95% CI (1.12-4.59). Conclusions: The study revealed that about two-thirds of patients with active TB remain undiagnosed and thus untreated. This may indicate the need for strengthening case detection at the community level. Furthermore, the high burden of TB among females and in the age group ≥45 years warrants appropriate measures to control the disease. © 2011 Tadesse et al.


Mihret A.,Armauer Hansen Research Institute
Virulence | Year: 2012

The immune response against Mycobacterium tuberculosis is multifactorial, involving a network of innate and adaptive immune responses. Characterization of the immune response, a clear understanding of the dynamics and interplay of different arms of the immune response are critical to allow the development of better tools for combating tuberculosis. Dendritic cells (DCs) are one of the key cells in bridging innate and adaptive immune response through their significant role in capturing, processing and presenting antigens. The outcome of interaction of M. tuberculosis with DCs is not fully understood and the available reports are contradictory were some findings reported that DCs strengthen the cellular immune response against mycobacterium infection whereas others reported M. tuberculosis impairs the function of DCs were infected DCs are poor stimulators of M. tuberculosis Agspecific CD4 T cells. Other studies showed that the outcome depends on M. tuberculosis strain type and type of receptor on DCs during recognition. In this review I shall highlight the recent findings in the outcome of interaction of Mycobacterium tuberculosis with DCs. © 2012 Landes Bioscience.


Getahun B.,Addis Ababa Institute of Technology | Ameni G.,Addis Ababa Institute of Technology | Ameni G.,Armauer Hansen Research Institute | Biadgilign S.,Jimma University | Medhin G.,Addis Ababa Institute of Technology
BMC Infectious Diseases | Year: 2011

Background: Tuberculosis (TB) is the leading cause of mortality among infectious diseases worldwide. Ninty five percent of TB cases and 98% of deaths due to TB occur in developing countries. Globally, the mortality rate has declined with the introduction of effective anti TB chemotherapy. Nevertheless, some patients with active TB still die while on treatment for their disease. In Ethiopia, little is known on survival and risk factors for mortality among a cohort of TB patients. The objective of the study is to determine the magnitude and identify risk factors associated with time to death among TB patients treated under DOTS programme in Addis Ababa, Ethiopia.Methods: This is a retrospective cohort study. Data was obtained by assessing medical records of TB patients registered from June 2004 to July 2009 G.C and treated under the DOTS strategy in three randomly selected health centers. A step-wise multivariable Cox's regression model and Kaplan- Meier curves were used to model the outcome of interest. Mortality was used as an outcome measure. Person-years of observation (PYO) were calculated from the date of starting anti-TB treatment to date of outcome and was calculated as the number of deaths/100 PYO. Statistical analysis SPSS version 16 was used for data analysis and results were reported significant whenever P-value was less than 5%.Results: From a total of 6,450 registered TB patients 236(3.7%) were died. More than 75% death occurred within eight month of treatment initiation. The mean and median times of survival starting from the date of treatment initiation were 7.2 and 7.9 months, respectively. Comparison of survival curves using Kaplan Meier curves method with log-rank test showed that the survival status was significantly different between patient categories as well as across treatment centers (P < 0.05). The death rate of pulmonary positive, pulmonary negative and extra pulmonary TB patients were 2.7%, 3.6%, and 4.3%, respectively. Body weight at initiation of anti-TB treatment (<35 kg), patient category, year of enrollment and treatment center were independent predictors for time to death.Conclusions: Most of the patients were died at the end of treatment period. This underlines the need for devising a mechanism of standardizing the existing DOTS programme and nutritional support for underweight patients for better clinical and treatment outcome. © 2011 Getahun et al; licensee BioMed Central Ltd.


Patent
Norwegian Institute of Public Health and Armauer Hansen Research Institute | Date: 2016-08-24

A method of detecting the presence of lymphocytes reactive with an antigen in an individual comprising contacting a lymphocyte sample containing T cells and/or B cells from the individual with an agent that non-specifically expands and/or activates a T cell and/or B cell population and said antigen, in order to generate a stimulated lymphocyte population. The detection of an indicator of T cell and/or B cell binding to said antigen in the stimulated lymphocyte population is indicative of the presence of lymphocytes reactive with the antigen being present in the individual.


Berhe G.,Mekelle University | Enquselassie F.,Addis Ababa Institute of Technology | Aseffa A.,Armauer Hansen Research Institute
BMC Public Health | Year: 2012

Background: Monitoring the outcome of tuberculosis treatment and understanding the specific reasons for unsuccessful treatment outcome are important in evaluating the effectiveness of tuberculosis control program. This study investigated tuberculosis treatment outcomes and predictors for unsuccessful treatment outcome in the Tigray region of Ethiopia. Methods. Medical records of smear-positive pulmonary tuberculosis (PTB) patients registered from September 2009 to June 2011 in 15 districts of Tigray region, Northern Ethiopia, were reviewed. Additional data were collected using a structured questionnaire administered through house-to-house visits by trained nurses. Tuberculosis treatment outcomes were assessed according to WHO guidelines. The association of unsuccessful treatment outcome with socio-demographic and clinical factors was analyzed using logistic regression model. Results: Out of the 407 PTB patients (221 males and 186 females) aged 15 years and above, 89.2% had successful and 10.8% had unsuccessful treatment outcome. In the final multivariate logistic model, the odds of unsuccessful treatment outcome was higher among patients older than 40 years of age (adj. OR = 2.50, 95% CI: 1.12-5.59), family size greater than 5 persons (adj. OR = 3.26, 95% CI: 1.43-7.44), unemployed (adj. OR = 3.10, 95% CI: 1.33-7.24) and among retreatment cases (adj. OR = 2.00, 95% CI: 1.37-2.92) as compared to their respective comparison groups. Conclusions: Treatment outcome among smear-positive PTB patients was satisfactory in the Tigray region of Ethiopia. Nonetheless, those patients at high risk of an unfavorable treatment outcome should be identified early and given additional follow-up and social support. © 2012 Berhe et al.; licensee BioMed Central Ltd.


Biressaw S.,Addis Ababa Institute of Technology | Abegaz W.E.,Addis Ababa Institute of Technology | Abebe M.,Armauer Hansen Research Institute | Taye W.A.,Addis Ababa Institute of Technology | Belay M.,Addis Ababa Institute of Technology
BMC Pediatrics | Year: 2013

Background: The introduction of Antiretroviral Therapy (ART) has brought a remarkable reduction in HIV-related mortality and morbidity both in adults and children living with HIV/AIDS. Adherence to ART is the key to the successful treatment of patients as well as containment of drug resistance. Studies based on caregivers' report have shown that adherence to ART among children is generally good. However, subjective methods such as caregivers' report are known to overestimate the level of adherence. This study determined the rate of adherence and its predictors using unannounced home-based pill count and compared the result with caregivers' report in a tertiary referral hospital in Ethiopia. Methods: A cross-sectional study was conducted between December 1, 2011 and January 30, 2012. The study participants were 210 children on ART and their caregivers attending pediatric ART clinic of Tikur Anbessa Hospital (TAH), Addis Ababa University. Caregivers were interviewed at the ART clinic using a structured questionnaire. Then, unannounced home-based pill count was done 7 days after the interview. Results: Caregiver-reported adherence in the past 7 days prior to interview was 93.3%. Estimated adherence using unannounced home-based pill count was found, however, to be 34.8%. On multivariate logistic regression model, children with married [aOR = 7.85 (95% CI: 2.11,29.13)] and widowed/divorced [aOR = 7.14 (95% CI: 2.00,25.46)] caregivers, those who were not aware of their HIV sero-status [aOR = 2.35 (95% CI:1.09, 5.06)], and those with baseline WHO clinical stage III/IV [OR = 3.18 (95% CI: 1.21, 8.40] were more likely to adhere to their ART treatment. On the other hand, children on d4T/3Tc/EFV combination [OR = 0.10 (95% CI: 0.02, 0.53)] were less likely to adhere to their treatment. Caregivers' forgetfulness and child refusal to take medication were reported as the major reasons for missing doses. Conclusion: The level of adherence based on unannounced home-based pill count was unacceptably low. Interventions are urgently needed to improve adherence to ART among children at TAH. Besides, a longitudinal study measuring adherence combined with clinical parameters (viral load and CD4 count) is needed to identify a simple and reliable measure of adherence in the study area. © 2013 Biressaw et al.; licensee BioMed Central Ltd.


Golassa L.,Addis Ababa Institute of Technology | Golassa L.,Armauer Hansen Research Institute | Enweji N.,Uppsala University | Erko B.,Addis Ababa Institute of Technology | And 2 more authors.
Malaria Journal | Year: 2013

Background: Prompt and effective malaria diagnosis not only alleviates individual suffering, but also decreases malaria transmission at the community level. The commonly used diagnostic methods, microscopy and rapid diagnostic tests, are usually insensitive at very low-density parasitaemia. Molecular techniques, on the other hand, allow the detection of low-level, sub-microscopic parasitaemia. This study aimed to explore the presence of sub-microscopic Plasmodium falciparum infections using polymerase chain reaction (PCR). The PCR-based parasite prevalence was compared against microscopy and rapid diagnostic test (RDT). Methods. This study used 1,453 blood samples collected from clinical patients and sub-clinical subjects to determine the prevalence of sub-microscopic P. falciparum carriages. Subsets of RDT and microscopy negative blood samples were tested by PCR while all RDT and microscopically confirmed P. falciparum-infected samples were subjected to PCR. Finger-prick blood samples spotted on filter paper were used for parasite genomic DNA extraction. Results: The prevalence of sub-microscopic P. falciparum carriage was 19.2% (77/400) (95% CI = 15. 4-23.1). Microscopy-based prevalence of P. falciparum infection was 3.7% (54/1,453) while the prevalence was 6.9% (100/1,453) using RDT alone. Using microscopy and PCR, the estimated parasite prevalence was 20.6% if PCR were performed in 1,453 blood samples. The prevalence was estimated to be 22.7% if RDT and PCR were used. Of 54 microscopically confirmed P. falciparum-infected subjects, PCR detected 90.7% (49/54). Out of 100 RDT-confirmed P. falciparum infections; PCR detected 80.0% (80/100). The sensitivity of PCR relative to microscopy and RDT was, therefore, 90.7% and 80%, respectively. The sensitivity of microscopy and RDT relative to PCR was 16.5 (49/299) and 24.2% (80/330), respectively. The overall PCR-based prevalence of P. falciparum infection was 5.6- and 3.3 fold higher than that determined by microscopy and RDT, respectively. None of the sub-microscopic subjects had severe anaemia, though 29.4% had mild anaemia (10-11.9 g/dl). Conclusions: Asymptomatic, low-density malaria infection was common in the study area and PCR may be a better tool for measuring Plasmodium prevalence than microscopy and RDT. The inadequate sensitivity of the diagnostic methods to detect substantial number of sub-microscopic parasitaemia would undoubtedly affect malaria control efforts, making reduction of transmission more difficult. RDT and microscopy-based prevalence studies and subsequent reports of reduction in malaria incidence underestimate the true pictures of P. falciparum infections in the community. PCR, on the other hand, seems to have reasonable sensitivity to detect a higher number of infected subjects with low and sub-microscopic parasite densities than RDTs or microscopy. © 2013 Golassa et al.; licensee BioMed Central Ltd.


Mihret A.,Armauer Hansen Research Institute
Virulence | Year: 2012

The immune response against Mycobacterium tuberculosis is multifactorial, involving a network of innate and adaptive immune responses. Characterization of the immune response, a clear understanding of the dynamics and interplay of different arms of the immune response are critical to allow the development of better tools for combating tuberculosis. Dendritic cells (DCs) are one of the key cells in bridging innate and adaptive immune response through their significant role in capturing, processing and presenting antigens. The outcome of interaction of M. tuberculosis with DCs is not fully understood and the available reports are contradictory were some findings reported that DCs strengthen the cellular immune response against mycobacterium infection whereas others reported M. tuberculosis impairs the function of DCs were infected DCs are poor stimulators of M. tuberculosis Ag-specific CD4 T cells. Other studies showed that the outcome depends on M. tuberculosis strain type and type of receptor on DCs during recognition. In this review I shall highlight the recent findings in the outcome of interaction of Mycobacterium tuberculosis with DCs.

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