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Armauer Hansen Research

Annual Report
Table of Contents

The year 2014 has been an exciting year at AHRI. Several large research projects were successfully conducted. The meningococcal carriage study in Arbaminch completed its field work and samples are being analyzed at both AHRI and Oslo collaborating laboratories. STREAM trial has been enrolling patients with multidrug resistant tuberculosis at both AHRI and St Peter's Specialized TB Hospital. Gondar University joined in as a third site to accelerate patient recruitment. The trial will move into Stage 2 in 2015 with more stringent procedures put in place to ensure high standards that can meet registration requirements. The Regional Bioequivalence Clinical Center at AHRI successfully completed two protocols and is preparing to apply for WHO prequalification. It is hoped that site visits will be conducted in 2015 to initiate the process. A total of 74 projects were running at the Institute in 2014. The number of publications topped 53, the largest in a year in the history of the Institute! This was a result of extensive collaboration of AHRI researchers with University and Health Facility colleagues in various parts of the country, often centered around postgraduate student training at AHRI and elsewhere. Most of the publications arose from work conducted at AHRI laboratories. The progressive increase in the number of AHRI publications is one sign of the expanding role and increasing maturity of AHRI postdocs and senior research assistants. It shows that AHRI has managed to generate competent research leaders who can realize the further expansion of the Institute and its extended hub function. Postgraduate training was further strengthened with three programs in 2014. These were the Emory-Ethiopia TB Research Training (EETBRT) Program funded by the National Institutes of Health Fogarty program, the Biomedical Sciences Postgraduate Training Program (BSPP) funded by Sida and the Brighton-Sussex Global Health Centre funded by the Welcome Trust where AHRI hosts students for co-supervision and research support in collaboration with Addis Ababa University and the other partners. The BSPP will enable 10 PhD candidates to acquire advanced skills in molecular techniques in Sweden. It is expected that the graduates will help catalyze biomedical research at regional universities in Ethiopia. To accommodate the increasing number of PhD students, AHRI has taken steps to acquire more laboratory equipment, more lab space and better access to reagents and supplies. Two new large autoclaves were received in 2014 and are being installed, both donated by Heal TB/USAID to support AHRI research. Field mobility will improve with the acquisition of several new vehicles purchased through Norad support. In the last 10 years, 73 MSc and 21 PhD students graduated from AHRI. One of the strategic aims of AHRI is to stay linked with as many of them as possible to strengthen collaboration and promote research in the universities and health facilities where many of them are currently employed. A survey is in progress to map where the alumni are. AHRI aspires to strengthen its hub function through continued collaboration with its international partners in advanced laboratories and its link with national institutions engaged in research and training. An example of a practical output in 2014 is the establishment of an immunology laboratory at the Amhara Regional Laboratory in Bahir Dar. Butajira Hospital received laboratory equipment to strengthen its research capacity in HIV, malaria and TB from EDCTP as a satellite sister institution of AHRI. AHRI received financial support from the MoH to strengthen clinical research. It plans to use this to enable peripheral hospital and university laboratories such as at Arba minch and Harar to conduct collaborative research (linked to postgraduate training whenever possible) on arboviral diseases, antimicrobial sensitivity and hepatitis, all significant problems at the sites selected. AHRI researchers have contributed to national and international scientific conferences and participated in several committee tasks at various levels. AHRI contributed to the WHO Meningitis Epidemic Guideline development in 2014. The AHRI Neglected Diseases Team is a member of the National Taskforce for NTD Control and has contributed to the national Master Plan and mapping of the national NTD distribution. The Leprosy team is similarly involved in the National Leprosy Program. The TB team promotes close links with regional programs and supports government initiatives. In 2014, the Capacity Building for Operational Research in TB (CORE-TB) program hosted at AHRI with financial support from TBCARE/USAID successfully achieved a milestone: all six first cohort research teams presented their findings at the 2014 International TB Conference in Barcelona and published articles in the peer review online journal Public Health Action! The second cohort of six other regions has completed its data collection and entered the analysis phase. The evidence generated by each team is likely to be of immediate benefit in solving the local problems because the research was led by program managers and responded to research questions posed by them. With increasing number of graduates from the universities and a rising demand for research space, AHRI is obliged to seek means to stay relevant and useful. One persistent challenge has been its administrative inefficiency and lethargic handling of logistic constraints. The Institute's management was strengthened this year through the establishment of a Procurement and a Finance Unit under the Scientific Director's Office. A Procurement and Finance Coordinator supervises the performance of the two units. Particular attention has been paid to ensure strict adherence of the units to good practice standards. It is expected that progress will be faster as team members build experience in handling assignments and improve efficiency. The Ethiopian government's strategy for Science, Technology and Innovation is to lay the ground work for a knowledge based economy of the future today. This requires institution building. AHRI had submitted an application to the Ministry of Health to be formally established as a Government Research Institute focused on biomedical, clinical and translational research serving as a sister Institute to the Ethiopian Public Health Institute. A draft legislation was developed by the legal unit of the Ministry of Health in consultation with AHRI and was subjected to stakeholder review. The appropriate Government organ is expected to deliberate on the document and take decision soon. The achievements of AHRI were only possible because of the continued support of the Federal Ministry of Health, Ethiopia, and its core funders Norad and Sida. AHRI is proud of its national and international research partners without whose contributions AHRI would not have reached this stage. Particular thanks go to the postgraduate students whose achievements we celebrate here. The AHRI/ALERT Ethics Review Committee and the AHRI Scientific Advisory Board are two very significant contributors to the quality of work at AHRI that have managed to keep it on track and to foster its national and international reputation. This year, the Ethiopian government provided AHRI with research funds to address clinical challenges. This move, building on the support of all the partners mentioned above, is very likely to lead to a new era for AHRI in the next years. Tuberculosis (TB) Team
The TB team; which was formally established in July, 2006, is the biggest team in terms of the number of projects, MSc and PhD students as well as research staff. In 2014, there are 6 projects on diagnostics, 13 on epidemiology, 4 on biomarker and 11 on basic biomedical research; which gives a total of 34 projects. Some of these projects are just in the initial phase, most are half way while the remaining are on their final phase. (Please see the full list of projects and status.) Diagnostics Research
University has been submitted as a patent application to the South African Patent Office. Smear based diagnosis depends on meticulous depends on accurate and timely diagnosis and proper management of cases. Several microscopic reading of multiple fields. In the case key areas needed in TB diagnostics of smears with scant mycobacteria, rare positive T include, 1) Improved sensitivity and cells can easily be missed because of suboptimal specificity of TB exposure tests (for latent assay conditions and worker fatigue. Imaging technology offers the potential to rapidly screen multiple slides and fields to simplify identification of immunocompromised patients such as in HIV disease, 2) rapid field friendly point of care tests rare positive acid fast mycobacteria and improve for TB diagnosis, 3) Improved efficiency of existing the sensitivity of smear positive TB detection. smear TB tests, 4) cheaper and faster TB culture Engineer Zebano Worku, an MSc student methods. Accordingly, the TB team is trying to candidate, is investigating automatic imaging technology to improve efficiency and accuracy of embrace innovation research and as part of this smear reading. The project, entitled "Optical initiative, 5 projects on diagnostics have been initiated. The first project is entitled ‘Improving the adjustment and stage automation of a microscope & automatic detection of mycobacterium species Immunological Approach'. Dr Markos Abebe and from sputum smear slides using image analysis techniques" is underway with financial support Dr Abraham Aseffa in collaboration with Dr Carol from AHRI core budget. Holm-Hansen at NIPH, Norway have been investigating on modifications of the standard QFT gold TB assay in order to improve detection of Mtb A related problem in TB control, particularly in immune reactivity in HIV positive patients known to resource limited settings is the high prevalence of have depressed cellular immune responses, and smear negative TB cases, typically diagnosed by this work has resulted in a patent application to the clinical and radiological criteria often several days European Patient Office in London. Further or weeks after initial presentation. Hence, rapid and accurate diagnosis of smear negative TB Norwegian volunteers will be conducted at Cr. cases is crucial for TB control. Recent research Carol Holm-Hansen's lab in Norway and will contribute to further definition of the specificity of mycobacteria accumulate lipid bodies and lose the assay among TB and HIV co-infected theoretically its potential for detection by the latter methodology. However, such bacilli can be Dr. Adane Mihret initially observed as a part of his detected by counter staining methods for lipid PhD thesis "Gene Expression and Cytokine bodies, raising the possibility that sensitivity for smear positive TB, and potentially smear negative Pattern of Pulmonary Tuberculosis Patients and TB might be improved through counter staining of their Contacts in Addis Ababa, Ethiopia "that plasma IP-10 levels successfully discriminated lipid bodies. In a project entitled "Lipid Bodies; can healthy contacts and TB patients. IP-10 and other they be Biomarkers for improved Diagnosis of Disease and Better Patient Management?", we plasma cytokines have been further evaluated in have commenced a study of 50 smear positive and collaboration with Stellenbosch University within 50 smear negative TB cases to evaluate the promising biomarkers able to distinguish TB potential of lipid body staining in comparison to disease from other pulmonary diseases with standard Ziehl-Neelson and Auramine-O staining similar clinical presentations. The collaborative approaches to identify mycobacteria in sputum and work with Dr. Adane Mihret and Stellenbosch culture specimens from these subjects. The project is supported by AHRI core budget and currently the proposal is submitted to AAERC. Development of a simple, cheaper and rapid Epidemiology research
method of TB culture is also a focus of the TB team. To this end, Befekadu Debebe, an MSc student, has evaluated the performance of 7% urrently, a number of epidemiological sheep blood agar (SBA) for the primary isolation of research projects are on-going. The goals Mycobacterium tuberculosis from pulmonary TB of these projects are to understand the suspected individuals under routine diagnosis dynamics, geographical clustering, drug condition, in a study entitled "Evaluation of culture Cr esistance pattern and molecular typing of of Mycobacterium tuberculosis on blood agar in TB in order to better understand the basis resource limited setting in Addis Ababa, Ethiopia". for transmission and virulence of the This media is routinely used in microbiology laboratories for the diagnosis of different bacterial species, and prior reports have suggested it's Studies on the molecular epidemiology of TB
utility in growth of MTB from sputum. Sputum in multiple regions within Ethiopia.
samples from 212 tuberculosis suspect individuals from selected health facilities were analysed by conventional smear microscopy, and cultured in Globally there are seven human-associated either conventional Lowenstein Jensen (LJ) media Mycobacterium tuberculosis lineages that are or 7% SBA agar. The sensitivity, specificity, differentially distributed with certain lineages positive and negative predictive value of blood predominating in certain geographical regions and agar media compared with LJ was 96.43%, human populations. Indio-oceanic (IO) - Lineage 1, 98.08%, 94.74% and 98.71%, respectively. West African Lineage I - Lineage 5, West African Importantly, the number of days of culture required Lineage II - Lineage 6 represent the ancient for detection of colonies was significantly less in branch of MTBC, East-Asian (EA) -Lineage 2, 7% SBA, median 14 (range 9-28) compared with East-African-Indian (EAI) - Lineage 3 and Euro- conventional LJH media, median 20 days (range American (EA) -Lineage 4 belong to the modern 12-39). The cost per culture in terms of branch of MTBC. The new lineage-Lineage 7 (L7) consumables and labour is comparable between was discovered at AHRI (from samples collected in the two methods. Thus, SBA may be a good Woldiya region of Ethiopia). Woldiya is the North- alternative of LJ medium for more rapid detection Eastern part of Ethiopian highlands. Lineage 7 is of MTB from sputum in resource limited settings. of considerable evolutionary interest because it represents a phylogenetic branch intermediate between the ancient and modern lineages of M. A final approach to potentially improve diagnosis of tuberculosis. L7 is confirmed to be associated with smear negative TB will be to evaluate mask the Horn of Africa. Searches in international sampling. Patients apply a surgical mask over their databases including more than 90,000 strains mouths for a short time period and are encourage identified L7 only among immigrant patients from Ethiopia and Somali. In a previous study MTB microdroplets of mycobacteria on a filter within the strains of L7 were isolated in the Central and mask surface. Following droplet elution, DNA is Northern part of Ethiopia with high degree in PCR amplified by Gene Xpert, the current gold Woldiya region. Genetic variability in MTBC clinical standard for PCR based TB diagnosis from isolates and clinical phenotypes can be better sputum samples. Initial pilot reports of this understood, and thus the reason of dominance of approach have been encouraging, and Dr. Baye certain MTBC lineages in certain geographical Gelaw from the University of Gondor is areas requires further investigation. collaborating with AHRI to evaluate this approach and sample collection has begun. The project, "Mask sampling as a method to detect tubercle In the Mycobacterium tuberculosis complex bacilli from smear negative pulmonary TB patients" (MTBC), a possible role for strain diversity in is funded by AHRI core. human tuberculosis (TB) is increasingly being suggested from work in various infection models. Significant differences among MTBC lineages have been reported in terms of their propensity to cause secondary cases in different human population, their progression to active disease in recently exposed household contacts, and their recognition by the human immune system. Most other related studies have reported associations between phenotypes. Additionally, the emergence of resistance to anti TB drugs, and particularly multidrug-resistant tuberculosis (MDR-TB) has National ethics review committees. Project specific been identified as one of the major obstacles to training has been given to the study team. The global TB control and pointing to the importance of project is funded by NIPH. Study specific pathogen genetic factors for the modulation of workshops have been conducted in South Sudan, infection outcome and epidemiology. Some of M. Sudan and Ethiopia (Addis Ababa and Bahir Dar). tuberculosis strains are reported to be strongly associated with MDR TB. Another epidemiological research in the Southern Region of Ethiopia is a PhD project by Yared However, the overall picture of the correlation ‘Molecular Epidemiology and Drug between mycobacterial genotype and clinical Resistance of Tuberculosis in Southern Region of disease characteristics is not well understood. Ethiopia'. The objective of the study is to describe The majority of studies focused only on a particular the molecular epidemiology and drug resistance strain types such as the Beijing genotype. There is a need to classify the whole variety of strains circulating in some particular area and to describe development and spread of drug resistance in phylogenetic lineages and associations with different settings of SNNPR and Shashemene clinical characteristics. area. A cross-sectional study design and survey will be employed at different study settings: health Elena Hailu, a PhD candidate from AHRI has institutions in Jinka of South Omo zone of SNNPR, started a new project entitled "Molecular at health institutions in Shashemene areas and epidemiology, drug resistance patterns of Mtb and Hawassa prison. A variety of individual and clinical outcome evaluation in Woldiya region, household characteristics in relation to TB Ethiopia." The main objectives wil be to further transmission will be assessed. All isolates of M. define lineage 7 and related lineages or tuberculosis strains will be screened for drug sublineages in smear positive and smear negative resistance and the drug resistance strains will culture positive patients in Woldiya, to find further undergo molecular characterization. In correlations between MTB genotypes and disease addition, all isolates of mycobacterium species will phenotypes and to determine anti-TB drug be typed to differentiate between individual strains resistance patterns of mycobacterial isolates. The within the main lineages and identify putative project is yet to be submitted to AAERC. transmission clusters. Sputum samples will be collected according to the National TB programme of the country and processed using standard In addition to the focus on Woldiya, several protocol. Funding: AHRI and Addis Ababa projects at AHRI are probing other geographically distinct regions in Ethiopia, including two in the southern regions, one in Benishangul Gumuz and one in Ambo region. Remote areas remain in Ethiopia for which little information epidemiology. An area in Ethiopia which has Dr Solomon Yimer, from the Norwegian Institute of received little attention is Benishangul Gumuz Public Health (NIPH), in collaboration with which boarders Sudan. An MSc project by Takele investigators from AHRI, South Sudan and Sudan, has initiated a study entitled‘Evolution of Novel Argicho, "Epidemiology and drug resistance pattern Mycobacterium tuberculosis Mycobacterium tuberculosis genotypes in East Africa and Clinical virulence trait assessment'. A Northwest Ethiopia: Resource Limited Setting", assessed the mycobacterial genotypic diversity recent spoligotyping study of M. tuberculosis and drug resistance pattern of M. tuberculosis isolates among pulmonary tuberculosis patients in complex, and the knowledge, attitude and practice the Amhara Region of Ethiopia showed the (KAP) of TB suspects towards tuberculosis. He presence of high level of diversity of strains among conducted a Health care institution-based cross- 237 M. tuberculosis isolates, in particular a high sectional study in Benishangul Gumuz and Awi proportion of SIT 910 and SIT 1729 which are only zone of Amhara region. 112 Smear positive samples were collected from study participants database and whose relationship to the previously from Benishangul Gumuz and the adjacent Awi identified Ethiopian lineage 7 remains to be zone of the Amhara region.DST results from 87 determined. The main objective of the Dr. Solomon's project is to decipher if distinct M samples revealed resistance to one or more drugs in 16.5% of the isolates, and monoresistance to tuberculosis lineages (SIT 910 and SIT 1729) are isoniazid in 6.9%. Multidrug resistance was associated with typical or unique clinical features observed in two cases, one of which was a and transmission pattern compared to other lineages. The project has obtained ethical tuberculosis isolates spoligotyping revealed 32 clearance both from the AHRI/ALERT and the previously unrecognized patterns suggesting the distribution of TB strains in this part of the country Disease incidence in clusters may be associated may differ significantly from elsewhere in Ethiopia. educational level, poor housing quality, crowded predominantly to SIT289, SIT53, SIT149, SIT37 living conditions, patient factors and alcohol abuse. and SIT134 strains. Out of 383 participants A mathematic modelling study found that targeting involved for the KAP study, about 5% had never control interventions to high incidence clusters heard about tuberculosis, two thirds knew that TB may have similar impact on the wider tuberculosis was transmitted by aerosols, about a third of respondents had no knowledge of means to throughout the remaining community. A thorough prevent TB. Half of respondents indicated that understanding of the temporal changes in the delay in health seeking behaviour was due to lack pattern of tuberculosis is thus important for tailored of knowledge, whereas 19% indicated that delay control measures. Dr Brita Askeland Winje from was due to reduced accessibility and affordability NIPH, Norway has established a collaborative of health care. In sum, these studies indicate that epidemiological study, ‘Spatial Analysis of although the current level of drug resistance is Tuberculosis Clustering in Dale District, Sidama apparently low in this remote region of Ethiopia, Zone, Southern Ethiopia' together with AHRI (Dr many respondents had a poor understanding of Markos Abebe) and University of Hawasa (Dr TB; hence, continued education and maintenance Daniel Datiko) to further probe pockets within the of high quality DOTs in the area is recommended country where TB prevalence rate are high, and so that treatment remains efficacious. case detection suboptimal. Similar studies are among the TB team strategic plan so as to Melaku Tilahun, MSc student, is studying the generate National TB cluster map. Such map will ‘Molecular Epidemiology and Drug Sensitivity help the National TB control program for targeted Patterns of Mycobacterium tuberculosis Isolated intervention and revise the existing policy on case from Tuberculosis Patients in and around Ambo detection strategies. The protocol is finalized; Town, Central Ethiopia'. While increasing funding is secured and ready for submission to information is becoming available on the strains of ethics review. Funding for this project is provided M. tuberculosis (MTB) circulating in Ethiopia in by the Norwegian Institute of Public Health and the general, no information is available on those in and Norwegian Health Association, Norway. around Ambo Town in particular. In this study repeated cross-sectional study designs will be Bovine TB: control strategies, prevention, used to recruit 152 human TB cases visiting health possible transmission to and from humans institutions from within and around Ambo Town for TB treatment. To date, equal numbers of smear positive pulmonary TB and TB lymphadenitis AHRI has for many years been engaged in subjects were recruited. From smear positive TB, research of bovine TB (BTB), which has significant 50 isolates have been obtained and shown to be impact on the dairy farming Industry and also may Mtb by PCR based RD9 deletional typing. 22 fine- contribute to human disease. Research projects needle aspirates from TB lymphadenitis lesions include 1) improvement in Bovine TB control exhibited growth, and of these 12 were confirmed strategies, 2) Development of a cattle vaccine to be Mtb by deletional typing. Spoligotyping and model against bovine TB, 3) Epidemiological drug sensitivity testing to further define the strain studies to probe possible transmission between diversity of these isolates is underway. Mtb and M. bovis between human and cattle. Cluster detection as an epidemiological A team from AHRI, Addis Ababa University, Ministry of Agriculture, Cambridge University and research tool to improve TB control in Animal and Plant Health Agency from UK under a consortium project ‘Ethiopia Control of Bovine Tuberculosis Control Strategies (ETHICOBOTS)' Cluster detection techniques for surveillance of working to provide a strong scientific tuberculosis incidence may support disease understanding for the development of sustainable control activities and reveal temporal changes in control strategies for BTB in Ethiopia that could the pattern of tuberculosis. One spatial clustering significantly reduce the high rate of BTB and its study from Dabat Region in northern Ethiopia zoonotic transfer in the expanding dairy sector, found smear positive tuberculosis to be clustered especially to more disadvantaged population geographically and concluded that this kind of sectors; minimise trading of BTB-infected dairy clustering may be common in the country. This has cattle to protect the national zebu herd and the implications, not only for investigating underlying livelihood of poor farmers and reduce the risk of etiology, but also for real-time intervention. zoonosis in high risk populations. The projected has now obtained ethical clearance from the National Research Ethics Review Committee and the most common aetiology of TB in humans, and soon will start sample collection. M. bovis the most common for bovine TB, yet each mycobacteria can cause TB in both humans and in Bovine tuberculosis is highly prevalent in intensive cattle, and little is known about the transmission dairy farms of the urban ‘milk-sheds' in Ethiopia. mechanisms involved and risks involved in groups Nonetheless, it is not a notifiable disease. As such as farmers exposed to cattle and vice versa. Ethiopia, like other emerging economies, cannot Importantly, a recent study at AHRI demonstrated afford to implement a test and slaughter control that poor dairy farm workers in peri-urban Addis strategy for both economic and social reasons, Ababa had a greater than 2-fold higher prevalence vaccination could be an acceptable alternative of TB than controls, raising the possibility that strategy. To approach this, Dr. Gobena Ameni cattle to human transmission may have occurred. leads a project entitled, ‘Establishment of a natural Dr. Araya Mengistu, a PhD student, is investigating ‘The Epidemiological Role of Cattle in the Mycobacterium bovis Bacillus Calmette-Guerin Occurrence of Human Pulmonary Tuberculosis in model to enable assessment of tuberculosis the Rural Community of Northwest and Northeast vaccine to prevent its transmission'. In this study, Parts of Amhara Region, Ethiopia'. The purpose of the performance of BCG in protecting bovine TB this study is to investigate the transmission of the was evaluated in 49 (23 vaccinated and 26 control) etiological agent of tuberculosis from cattle to Holstein-Friesian calves inserted into a herd with human and vice versa in North Wollo zone of the high bovine TB prevalence. Additionally, the Amhara region, Ethiopia. This study evaluated intranodal challenge model for the evaluation of vaccine efficacy was ascertained. The calves were Questionnaires administered to cattle owners vaccinated with the equivalent of 5 human doses of BCG Danish or with placebo via the transmission of TB. Nearly half of interviewed subcutaneous route when 2 weeks old and then cattle owners drank raw milk from cattle, and exposed 6 weeks later to the infected herd where approximately 60% ate raw beef. More than 75% they were kept in contact with infected donor did not know the benefit of boiling milk in animals for about one year. Gamma interferon and preventing TB. About 80% of respondents did not comparative intradermal tuberculin tests, gross remove or isolate their sick cattle, and a and microscopic pathological examinations as well substantial percentage of household cohabited the as bacteriological culturing including colony same dwelling with their cattle. counting and molecular typing were used to evaluate the performance of BCG. The result In the first cohort, cattle owners with suspected TB showed a 63% reduction of gross pathology in the were recruited and evaluated for TB, and their vaccinated calves of as compared the non- cattle skin tested for TB. Only 4 of 134 cattle vaccinated calves (p<0.05). Regionally, gross owners tested positive for TB, whereas 10 cattle of pathology in the lung lobes, pulmonary, head and 381 tested positive by tuberculin skin testing. 9 alimentary tract lymph nodes was reduced by 59, owners of positive cattle were identified and 46, 87, and 88 %, respectively. The percentage of interviewed, and of these none had TB, even animals presenting without gross pathology though 6 of 9 routinely drank raw milk from cattle. increased by 24 % in the BCG vaccinated group. In the second study, 35 cattle owning households In conclusion, BCG vaccination of cattle in Ethiopia with a known human case of TB were recruited could constitute a potent tool to reduce pathology along with 105 cattle owning households without and thereby animal to animal transmission. This known TB. Cattle owned by each household were project has two parts, evaluation of the protective assessed for TB by skin testing. The results efficacy of BCG, and validation of the intranodal showed that whereas about 15% of households challenge model for vaccine efficacy testing in without human TB owned cattle with bovine TB, bovine. The latter objective is planned to be nearly 48% of households with TB owned cattle performed during the coming 6 months. The with bovine TB, a threefold increase. Studies are project is funded by Bill and Melinda Gates planned to determine whether the aetiology of Foundation and is performed in collaboration with bovine TB in these cattle is M. bovis or Aklilu Lemma Institute of Pathobiology, Addis alternatively MTB. In the third cohort, cattle owners with recently diagnosed TB were identified and Diagnostic and Investigation Centre, Sebeta, their disease causing mycobacteria isolated and Ethiopia; the School of Veterinary Medicine, characterized. 50 isolates were identified after University of Surrey, U.K., and Animal Health and culture, and all found to be MTB. Further molecular Veterinary Laboratories Agency, Surrey U.K. characterization by spoligotyping revealed that most isolates belonged to either East-Africa-Indian TB may potentially spread between humans and (57.4%), or Euro-American (34.0%) lineages, with animals and between animal species MTB is by far Ethiopian (lineage-7) (4.3%) and undetermined (4.3%) accounting for the remaining strains. miRNA and inflammation biomarkers in Ethiopian International Types (SIT) 21, 25, 26, 35, 53, 109, Mycobacterium tuberculosis and HIV during anti- 149 and 289 were found as clusters, and a total of tuberculosis and antiretroviral treatment" with the 8 clusters were identified suggesting current aim of identifying markers that can be used for ongoing TB transmission. detection of different groups of patients. Sample collection is completed. Preliminary tests on qPCR Collectively, this study identified a number of high for miRNA is done. A student has been recruited risk activities commonly practiced by cattle owners from AAU to take part in the project and will be which theoretically would be permissive for cattle travelling to Sweden for a 2 months attachment. to human transmission or vice versa. Consistent Peripheral blood collected in PAXgen tube will be with this, cattle-owning households with TB were sent to Sweden for microarray analysis and the nearly three times more likely to have cattle with results will help to select candidate miRNA to be TB than cattle-owning household without TB. analysed by real time PCR. Nonetheless, the causative agent for TB among cattle owners was invariably MTB and not M. A critical component of vaccination is to generate bovis. Thus if transmission occurs between antigen-specific humans and cattle in Ethiopia, it is most likely due lymphocytes of sufficient quantity and quality to to Mtb and potentially moves from humans to provide long term protection against re-infection. In cattle (and potentially subsequently back to spite of considerable advances regarding immune human). Alternatively, the observed associations response to Mtb, it is still challenging to interpret between cattle and human TB may be due to other results of vaccine trials. This is partly due to lack of definitive markers of protection, which could be transmission. Further work needs to establish used to assess vaccine efficacy. The T-cell whether and how common Mtb can be identified in Specific Adapter Protein (TSAd) is considered to TB disease bearing cattle in these Ethiopia, and be a key regulator of T-cell polarity and a possible molecular similarities between putative Mtb strains marker for T-cell memory. Meseret Habtamu (PhD identified in cattle and those in human. candidate) in a project entitled, "Molecular markers and mechanisms of T cell memory" will be looking Biomarker Research
at the role of TSAd in maintaining T cell memory responses by comparing TB patients and healthy individuals. The project is funded by AHRI core budget and Norwegian Quota program. iomarkers are biological properties or molecules that can be detected and measured in blood or other tissues. Biomarkers may be associated with either evaluation of the relative frequency of different T normal or diseased processes in the body. cell phenotypes (central, effector, terminally B AHRI has been involved in studies to find differentiated memory and naive T cells) in blood associations between clinical states of TB from TB patients at base line and following and biomarkers such as cytokines, treatment (Dr. Markos A). This project is at its final apoptotic markers and more recently stage of data analysis. Evaluation of serum inflammatory proteins such as C-reactive protein, neopterin, procalcitonin and metalloproteinases as biomarkers distinguishing different clinical stages MicroRNAs are small, non-coding RNA fragments of TB disease is being undertaken by Dr Adane M. that can repress protein expression by targeting mRNA. It was recently shown that many microRNAs are involved in the regulation of Basic Biomedical Research
immune responses, including expression of proinflammatory cytokines to different pathogens. number of basic biomedical research on Among others, Toll-like receptor (TLR) signalling TB are undergoing at AHRI. Most are pathways have been shown to be tightly regulated oriented towards better understanding by microRNAs Mtb infection may trigger several the host immune response in different TLRs, particularly TLR-2, TLR-4 and TLR-9. groups of individuals. A study by Dr Liya However, the role and the expression profile of Wassie, "Characterization of innate and different microRNAs during Mtb infection of memory phenotypes to TB and hormone myeloid target cells are not yet known. Dr modulations in apparently healthy children and Marianne Jonson from Lund University, Sweden, adolescents across age"is aimed at defining the in collaboration with Dr Markos Abebe and Dr influence of hormone modulation during puberty on Abraham Aseffa are looking at the "Expression of the host immune response to TB.The study will compare cohorts of school aged children and In the second project, Dr. Fekadu Desta is adolescents before and after puberty. To date, evaluatingbovine lymphnode lesional cells, in a optimization of lab procedures and sensitization of project entitled "Immunophenotype and Functional participants have been performed. Different innate Characterization of T Cell Subset and Monocyte- and adoptive immune markers will be measured Macrophage Lineage cells within Lymph Node using flow cytometry, RT-PCR and ELISPOT Granulomas and peripheral blood of calves approaches. The project is funded by EDCTP (TB- Exposed to Natural Mycobacterium bovis Infection" TEA grant) and AHRI core budget, and done in Previous work by Dr. Gobena and collegues (see collaboration with Staten Serum Institute (SSI). above) has established a natural infection model whereby young calves are transplanted to a herd PhD candidate Martha Zewdie is addressing the with high TB prevalence, and disease progression role of regulatory T cells in Tuberculosis (TB) can be monitored with or without prior vaccination. disease, latent TB infection (LTBI), and vaccinated This study will characterize lesional cells in individuals in a project entitled "Analysis of comparison with PBMC to gain insights into regulation of immune responses in Tuberculosis" mechanisms of BCG- induced protection of TB The immune response in TB patients and LTBI has disease. Paired PBMC-lymph node samples from been assessed by measuring IFN-γ production by either BCG vaccinated or unvaccinate calves with ELISPOT and regulatory T cell subsets analyzed high risk exposure to TB have been isolated and in these study groups by flowcytometry. Results to cryopreserved. Flow cytometric phenotypic and date revealed an increase in a specific population functional characaterization of lymphocyte and of regulatory T cells, actively proliferating memory monocyte/macrophage samples is underway. In parallel, complementary CD4+CD25+FOXP3+CD45RO+Ki67+, in TB patients studies will evaluate in situ cell surface phenotype when compared to LTBI.A manuscript reporting and cytokine expression from parafin embedded this novel finding is underway. Future work will tissue from these animals. In collaboration with further define this and other regulatory subsets IPB, AVLRA, and AHRI, AHRi core funded. through analysis of gene expression profiles and additional Treg markers. The project is funded by Ethiopia has a rich history of traditional medicine EDCTP, and done in collaboration with SSI. from local plant extracts. To evaluate whether any of these extracts have anti-mycobacteriocidal Most studies of TB pathogenesis, particularly activity, a PhD student, Wubayehu Kahalw, in a those in human and cattle, have relied on use of project entitled, "Activity Test, Isolation and peripheral blood mononuclear cells (PBMC). Two Chemical Structure Elucidation of Anti-tuberculosis studies are addressing pathogenic mechanisms Constituents from Plants Used in traditional using extracted cells from tuberculosis lesions. In Medicine in Ethiopia", has prepared chloroform the first, we investigated apoptoic markers. and/or methanol and/or acetone extractions from a Previous work at AHRI by Dr Markos Abebe, number of local plants including (Otostegia thatCD14+ monocytes are less susceptible to Americana,Vernonia Amygdalina). These extracts apoptosis by over expressing FasL and down will be evaluated for their activity against Mtb in an regulating Fas and TNFs. To gain further insight in vitro model with Mtb infected THP-1 human into how this mechanism might contribute to TB macrophage cells. pathogenesis, we sought to evaluate these and other apoptosis markers using cells collected aternal and child health are among the within TB lymphadenitis lesions.Nejat Juhar (MSc top priority areas of both the MDG and candidate) did her project on comparing apoptosis the Federal Ministry of Health. AHRI related molecules on macrophages and T-cells in has continued to conduct research in peripheral blood and lymph node of TB this area. One project, by Silesh Abdessa, aimed to define more understanding how the bacilli interacts with the precisely using PCR methodology the immune cells at the site of infection. The study, prevalence of female genital tuberculosis. The "Comparison of apoptotic markers on macrophage results indicated that female genital TB accounts and T cells in peripheral blood and Lymph node for up to 5% of all TB in this country. A second from TB patients and controls"showed a difference project, entitled "Mycobacterium tuberculosis in the expression of apoptosis related molecules at specific immune response among HIV infected the site of infection and peripheral blood as well as pregnant women" by MSc student Malet Birku, has on macrophage and T-cells. The study also addressed impact of the combination of pregnancy showed a decrease in macrophage apoptosis in and HIV infection on TB specific responses. the lymph node, which may help the bacilli to LTBI, as assessed by QFN and TST tests was replicate and evade the host immune response.

significantly less in HIV+ pregnant women (19%) responses were very weak throughout. These compared with HIV- pregnant women (29%). Using studies reveal the impact of both pregnancy and sensitive Mtb-specific single cell ELISPOT assays, HIV infection in reduction of Th-1 IFN-g responses HIV+ pregnant women exhibited significantly lower in LTBI, as well as the influence of pregnancy in IFN-g responses, but higher IL-10 responses than augmenting immunosuppressive IL-10 responses. Grant Applications
1. Biomarkers for tuberculosis diagnosis and 2. Effect of maternal factors on neonatal treatment response in Ethiopia (Grant BCG vaccination (Grant submitted to application for NIH/NIAID together with experts at Emory University, status- rejected) (Dr Liya W) Attendee
Conference/workshop/training title
University of Oslo, Norway To run experiments at Prof Spurkland's lab. University of Oslo, Norway Course work and laboratory training Dr. Markos Abebe Khartoum To train EvoTB-2 project staff on sample collection To participate in the annual THY-B04 project meeting To participate in TB HIV research dissemination workshop World TB day at AHRI
by students from different Schools (137), commemorated at AHRI by organizing invited guests from different Associations open day event to students, visitors and (28) and staff from ALERT and AHRI (35) invited guests to AHRI. The program (Few pictures taken during the laboratory laboratory visit. The event was attended List of TB Researches at AHRI
Project type/PI
Diagnostics research
Improving the sensitivity of QFT TB Gold assay AHRI project (Markos A) Patent application submitted to the AHRI core budget using T cell Blast (ISQA) European Patent Office (EPO) Methods of Diagnosing tuberculosis. Consortium projects Patent application submitted to the South African Patent Office Optical adjustment and stage automation of a AHRI core budget microscope & automatic detection of Procurement of equipments mycobacterium species from sputum smear slides using image analysis techniques Evaluation of culture of Mycobacterium Thesis defended, manuscript in tuberculosis on blood agar in resource limited setting in Addis Ababa, Ethiopia Validation of Tuberculosis Diagnostic Algorithm Thesis defended, AHRI core budget and Newly Emerging Tests for the Diagnosis of 2 manuscripts in preparation Childhood Tuberculosis in Ethiopia Mask sampling as a method to detect tubercle Consortium project Sample collection undergoing AHRI core budget bacilli from smear negative pulmonary TB Lipid Bodies; can they be Biomarkers for Protocol development improved Diagnosis of Disease and Better Patient Management? Epidemiology research
Molecular Epidemiology and Drug Resistance of Ongoing: Sample collection AHRI core budget Tuberculosis in Southern Region of Ethiopia Spatial analysis and clustering of tuberculosis in SNNPR in Ethiopia: A Population Based Funding secured, protocol Prospective Cohort Study submitted for ethics review Drug resistance pattern in lineage seven and AHRI core budget other lineages of mycobacterium tuberculosis on archived isolates Molecular Epidemiology and Drug Sensitivity Ongoing: sample collection, TB AHRI core budget Patterns of Mycobacterium tuberculosis Isolated from Tuberculosis Patients in and around Ambo Town, Central Ethiopia Determinants of MDR-TB in Eastern part of AHRI core budget Ethiopia Dire Dawa Data collection completed and analysis started Molecular Epidemiology and Drug Resistance of AHRI core budget Mycobacterium tuberculosis Among New Smear Positive Pulmonary Tuberculosis Cases in eastern Ethiopia A community based study on the prevalence of Tuberculosis cervical lymphadenitis in Yilmana Densa district, Amhara region, Ethiopia Prevalence of Endometrial Tuberculosis and Thesis defended, Manuscript in AHRI core budget Characterization of Isolates among patients undergoing endometrial biopsy at Tikur Anbesa specialized Hospital, Addis Ababa, Ethiopia Molecular Epidemiology, drug resistance pattern of M. tuberculosis and clinical outcome evaluation in Woldiya region, Ethiopia Phenotypic and genotypic assessment of drug AHRI core budget resistance tuberculosis in Dessie and surrounding The role of Cattle in transmitting the causative Data analysis and thesis writ up AHRI core budget agent of tuberculosis in two Zones of the Amhara Epidemiology and Drug resistance pattern of AHRI core budget Mycobacterium tuberculosis in North West Ethiopia: Resource limited region. Ethiopia Control of Bovine Tuberculosis Strategies Consortium project Submitted for National Ethical ZELS program, UK Establishment of a natural transmission model in Experiment and data analysis cattle to validate the BCG challenge model and to completed, manuscript write up enable assessment of TB vaccine to prevent TB transmission Biomarker research
Expression of miRNA and inflammation Postdoc (Marianne J) Ongoing: Sample collection AHRI core budget biomarkers in Ethiopian individuals singly or dually completed, QFT test done. RNA and Lund University infected with Mycobacterium tuberculosis and HIV during anti-tuberculosis and antiretroviral Evolution of immune response during treatment Ongoing: Data analysis Serum Inflammatory proteins as biomarkers for Samples collected and reagent discriminating different tuberculosis infection bought, ELISA test underway Molecular markers and mechanisms of T cell AHRI core budget Basic biomedical research
Evolution of Novel Mycobacterium tuberculosis Postdoc (Solomon Y) Ongoing: ethical clearance, training genotypes in East Africa and Clinical virulence given to study team trait assessment Immunophenotype and Functional Ongoing; Optimization AHRI core budget Characterization of T Cell Subset and Monocyte- Macrophage Lineage cells within Lymph Node Granulomas and peripheral blood of calves Exposed to Natural Mycobacterium bovis Infection Activity Test, Isolation and Chemical Structure Elucidation of Anti-tuberculosis Plant extract ready for in vitro Constituents from Plants Used in traditional Medicine in Ethiopia Characterization of innate and memory phenotypes to TB and hormone sample collection modulations in apparently healthy children and adolescents across age (TBTEA) Analysis of regulation of immune responses Data analysis, thesis submission April 2015 Mycobacterium tuberculosis specific AHRI core budget immune response among HIV infected Thesis submitted Comparison of apoptotic markers on Ongoing: Thesis write-up AHRI core budget macrophage and T cells in peripheral blood and Lymph node from TB patients and controls. Dysfunctional immunity in TB Manuscript in preparation Institute, AHRI core Effect Of Diabetes Mellitus on T-Cell Sample collection undergoing AHRI core budget Immune Response among Pulmonary Tuberculosis Patients In Addis Ababa, Ethiopia Bacteriology Team
AHRI Bacteriology team was established in 2006 to conduct epidemiological and molecular studies on common bacterial diseases. The aim of establishing the bacteriology team is to lead, plan and coordinate research activities related to meningitis, pneumonia, typhoid fever and other infections caused by pathogenic bacteria. Moreover, the team plays a significant role in capacity building activities of AHRI. As a result of this, MSc and PhD students research projects are provided all the necessary support such as supervision, funding and laboratory space at the bacteriology laboratory to conduct their research. The overall goal of the team is to characterize and identify etiologic agents of diseases in different geographical areas of the country so as to provide research based information to policy makers. entitled "Bacterial Meningitis actual disease burden report and disease severity in non-epidemic season in Ethiopia by use of real time  Wude Mihret [Senior Researcher]  Dr. Demissew Beyene [Post-doctoral sequence typing and cytokine detection assay" is integrated with the main study and the student  Tsehaynesh Lemma [Medical Microbiologist] is coordinating this consortium study both at field Dr Mekonnen Teferi [Research Assistant]  Elena Hailu [Research Assistant]  A total of 163 Study participants clinically Biruk Yeshitela [Research Assistant] diagnosed to have bacterial meningitis were recruited from Hawassa, Gondar and Tikur Anbessa University Hospitals. Bacteriological  Mahlet Tadesse [Laboratory Technologist] and molecular diagnosis were run to detect Neisseria meningitides, Haemophilus influenzae Melaku Yiedenekachew [Biologist] and Streptococcus pneumoniae among 139 Wondewosen Tsegaye [PhD student] study participants whose samples and case  Nigus Zegeye [MSc student] record forms (CRFs) collection were completed. Among the 139 patients suspected with bacterial Project Lists
meningitis admitted at the three hospitals in Ethiopia during 2012-13, 46 harbored either serogroup Disease burden and severity of bacterial pneumococci, reinforcing the need for intensified meningitis in Ethiopia in non-epidemic affordable meningitis vaccines for the African meningitis belt. Remaining work includes serum cytokine analysis for all study participants to [PI: Professor Dominique Caugant and Dr determine associations with bacterial etiologies, meningococcal serogroups defined at AHRI and for molecular identification of non-typable Ethiopia is one of the meningitis belt countries an area with repeated occurrence of meningitis Manuscript preparation for the completed portion epidemics in Sub-Saharan Africa. This study is of the work is in progress. designed to investigate the actual burden of bacterial meningitis during non-epidemic periods since only limited data is available in this regard. An MSc student capacity building research Funding Source: The Norwegian Research
suspected patients from all age groups in St Norwegian Institute of Public Health (NIPH). Paul's hospital, Addis Ababa. 185 blood culture samples were analyzed from eligible patients. About 23% of the samples were positive for Typhoid Fever Surveillance in Africa bacteria, and more than 10 species of bacteria were identified. The bacterial type and DST results were sent to the clinic to assist in clinical [PI: Dr Florian Marks, Dr Abraham Aseffa; management of the patient. The relevant data were double entered in to the database, and Status: Completed] final analysis remains. In collaboration with International Vaccine The impact of Ten-valent pneumococcal Institute (IVI), TSAP began recruitment in Butajira from March 2012 with the objective to estimate the incidence of typhoid fever in Africa Streptococcus pneumoniae using a standardized surveillance method currently utilized across 10 different African countries. TSAP recruited about 900 febrile phenotypic and genetic diversity of patients from four health facilities serving 10 isolates from Addis Ababa, Ethiopia surveillance site. Blood samples these cases were cultured using the Bactec system, and [PI: Dr Wondewosen Tsegaye; Status: On- further subculture and species identification was performed. Strain sequencing will be performed by IVI to define circulating S. typhi strains in The objectives of this project are to determine Ethiopia which will assist in matching needs with the impact of the PCV 10 vaccine on current vaccine candidates. In parallel, TSAP aimed to determine the health care seeking pneumonia by evaluating pre- and post-vaccine behaviour of the catchment population through samples, and to analyze the phenotypic and administration of a health care utilization survey genetic diversity of pneumoccal isolates. Pre- vaccination specimens from newborns were administered to 592 selected households, data collected from 7 health centers in Addis Ababa. entry and cleaning and analysis is underway. From 789 study participants we identified a total The final results will be reported by IVI. of 512 bacterial isolates, the most common of which staphylococcus (171), Moraxella catarrhalis (104), and Hemophilus influenza (31). Post-vaccination evaluation is underway, and thus far we have obtained samples from about 20% of Characterization those initially vaccinated, resulting to date in the Susceptibility Patterns (CASP) of blood culture isolates from septicemic patients Moraxella catarrhalis, and 9 Haemophilus at St Paul's hospital, Addis Ababa, molecular analysis of genes responsible for resistance to erythromycin and penicillin are underway. [PI: Adugna Nigussei; Status: On-going] Funding Source:
CASP was initiated in December 2012 with the AHRI core budget. aim to define the prevalence of bacterial species and their antimicrobial sensitivity pattern from

Throat carriage rate and antibiotic susceptibility streptococcus in children with rheumatic fever Specialized Hospital, Addis Ababa, Bacteriology Team A Comparative Study of Blood Culture [PI: Nigus Zegeye; Status: This project iscompleted] and Widal test in the Diagnosis of Typhoid Fever in Febrile Patients in Isolation of group A streptococci from children selected Health Centers, Addis Ababa, having rheumatic heart disease is a MSc project aimed to determine the effectiveness of secondary antibiotic prophylaxis, and to further characterize [PI: Biruk Yeshitela; Status: On-going] isolated. Throat sample, blood specimen and risk factors associated with streptococcal throat The primary objective of this study is to compare infection have been collected from children at the diagnostic performance of Widal test and Tikur Anbessa hospital. Throat culture and blood culture in the diagnosis of typhoid fever in biochemical tests have been done to isolate febrile patients in Addis Ababa, Ethiopia. betahemolytic streptococci and stored for further Typhoid/paratyphoid (enteric) fever is a systemic tests. Out of 234 participants, throat carriage prolonged febrile illness which is an important rate of β-hemolytic streptococci was 23.9 % health problem in many developing countries (56/234). Children who received antibiotic and is caused by certain Salmonella serotypes including S. typhi, S. paratyphi A, S. paratyphi B significantly lower β-hemolytic streptococcal and S. paratyphi C. S. typhi is a highly virulent, throat carriage than those sampled 4 weeks host-restricted invasive pathogen that affects after injection (p=0. 004). Of the β-hemolytic only humans. Most of the health burden occurs streptococci identified, 4 were S. pyogenes, and among people of low-income regions. The Widal Streptococcus dysgalactaie subsp. equisimilis test has been in use for more than a century as possessing Lancefield group A, C and G were an aid in the diagnosis of typhoid fever. also isolated. Six different emm gene types with However, the predictive value of this test has one newly discovered subtype (stGrobn.1) were been debated. The goal of this study is therefore to evaluate the Widal test for sensitivity and transferase in strain emm 68.2 (multidrug sensitivity in a case control study.343 individuals resistant strain) had N-linked glycosylation were recruited, laboratory analysis is ongoing carrying a unique HexNAc-deoxyhexose, a and demographic and risk factors data collected post-translational from study participants is currently being entered by the data management and statistics unit. streptococci were susceptible to penicillin except
S. agalactaie. Erythromycin and tetracycline
resistant S. pyogenes were identified.
Funding Source: AHRI core budget.
Impact of meningococcal conjugate NIPH in Oslo, Norway. Data entry and cleaning vaccines on serogroup A transmission in for both the cross sectional and longitudinal Ethiopia – mechanism and dynamics of studies are completed and shortly data analysis clearance of asymptomatic carriage - will be started. The Ethiopian carriage study Funding Source: The Norwegian Research
Counsel Collaborating Institution (s): The
[PI: Professor Dominique Caugant and Dr. Norwegian Institute of Public Health (NIPH), Demissew Beyene; Status: This project is Nationalities and Peoples Regional Health Bureau, Arba Minch University and Arba Minch To eliminate meningitis epidemics caused by General Hospital. Neisseria meningitis, a new serogroup A meningococcal conjugate vaccine, MenAfriVac, was developed by the Meningitis Vaccine Project (MVP). The vaccine was introduced in Surveillance of Bacterial Meningitis in mass vaccination campaigns in Burkina Faso and parts of Mali and Niger in December 2010. Roll-out of MenAfriVac is planned to encompass all 25 countries of the African meningitis belt by [PI: Professor Dominique Caugant and Dr. Abraham Aseffa; Status: On-going] The aim of the project is to demonstrate the The aims and objectives of this study is to ability of MenAfriVac and other conjugate characterize the etiology of bacterial meningitis vaccines, to reduce pharyngeal carriage, and in 8 selected hospitals in Ethiopia during the thus, transmission of the pathogen. The study period 2014-2016 and to study antigenic will investigate the dynamics of carriage variation, molecular variation and antibiotic clearance in correlation with vaccine-induced susceptibility patterns among the patients' antibody responses in serum and saliva. By isolates. To date, 41 patients have been studying the dynamics of carriage clearance and recruited from Hawassa referral hospital, and 3 correlating carriage to antibody concentrations in patients recruited from Arbaminch hospital. saliva and in serum, the study may provide Laboratory analysis is ongoing. further knowledge on the mechanism of action of conjugate vaccines and determine an antibody Funding Source: The Norwegian Research
threshold necessary to prevent carriage. Norwegian Institute of Public Health (NIPH). Both the sample collection and laboratory activities of the project are completed. A total of Capacity building
7723 pharyngeal swabs have been collected from multiple sites around Arba Minch. All these samples  The team provided training for two PhD biochemically tested with Oxidase, GGT/ONPG students and two MSc students. and agglutination tests to identify pharyngeal  RT PCR training is given for 7 EPHI carriage and to serogroup them. A total of 74 bacteriology staff, 1 Hawassa university carriers with different serogroups were identified. staff and 5 AHRI staff. Out of the 74 carriers identified, 65 carriers were grouped into the vaccine and control groups and all of them were followed. Appropriate clinical specimens (blood, saliva and blood spot) were National: Addis Ababa University, Gondar
collected for immunogenicity testing. The immunogenicity tests will be performed at the University, Saint Peter's Hospital, Arba Minch University, Arba Minch General Hospital, SNNR Vaccine Institute (IVI),University of Bergen, health bureau, Amhara Regional Health bureau, Norway, KIT, Biomedical Research Institute, The Federal Ministry of Health of Ethiopia, ALERT hospital, EHNRI. Diseases Research Institute (IDRI), USA, The Norwegian International: London School of Hygiene &

Neglected Tropical DiseaseTeam
In 2013 the NTD-Malaria team was involved both in research and professional services to the Federal Ministry of Health (FMoH). As a member of the national Neglected Tropical Disease Control task force, the team was involved in the development of NTDs five year master plan and launching workshop. In addition, the team participated in the preparation of the Map of NTDs in Ethiopia, in the revision and editing of the guideline for Diagnosis, Treatment and Prevention of Leishmaniasis in Ethiopia 2nd edition June, 2013. Research activities comprised three leishmaniasis related projects and three Malaria related projects, and 4 articles in peer reviewed Journals were published. Moreover, the team has contributed in human capacity building; 5 PhD students were linked with the research activities and in collaboration with Addis Ababa University and 1 MSc student thesis was successfully defended. Highlights: 2014
Compared to the preceding year, our team in The team identified the need to established 2014 had unique experiences. Leishmania culture capacity, and trained staffs at the Bahir Dar, Amhara Regional laboratory (Figure 2). In response to lack of cytocentrifuge our PhD student proposed designing a bucket with accessories which could be interchanged into the ordinary centrifuge rotor to produce hybrid cytocentrifuge; this was funded by the Ethiopian Science and Technology Ministry. Partnering with a private engineering service provider, the team constructed and tested the functionality of a prototype Cytocentrifuge (figure 1). Figure 2. Team members training the regional staff Continuing its collaboration with the FMoH as member of the NTD control task force, the team is participating in the onchocerciasis delineation work. This year the team published 10 articles in peer reviewed journals. In addition there are 2 manuscripts publication in Plos One and the other under review Figure 1. Above the new hybrid Cytocentrifuge bucket; accessories below when it is fitted in the Geoinformatics and 3 under preparation. The normal centrifuge rotor. details of Projects ongoing and completed in 2014, other activities and achievements of the team are detailed as in below. Research and Capacity Building
Significant contributions of our research findings include: (for more information refer to the publications listed below): In Ethiopia, over 83.6% the population lives in rural areas with subsistence mixed farming practice. Infectious diseases and malnutrition With basic biomedical and epidemiological are important concerns in the society. Despite the political commitment and effort to control infectious disease, malaria and leishmaniasis 1. It is more than a decade since chloroquine still are among the top public health threats (CQ0 was withdrawn yet 100% of the especially for the poorest of the poor; the rural parasites from both symptomatic and community. Malaria is the 3rd among Ethiopia's asymptomatic cases from south-central disease burden list and 75% of the area of the Oromia still carry the pfcrtK76T mutation country-- representing 68% of the population--is 2. No K-3 propeller mutations implicated in malarious. Leishmaniasis is a re-emerging Artemisinin resistance previously reported public health problem with increasing number of in Southeast Asia was found in P. reported cases and appearing in new areas falciparum from twelve sub-Saharan Africa previously not known to be endemic. The countries showed population at risk of leishmaniasis is estimated to be over 3 and 29 million for visceral and Comparing smear microscopy with molecular cutaneous leishmaniasis, respectively. The techniques showed a high rate of species annual incidence is approximately 2500 to 4000 mismatch: a higher proportion of P. vivax cases cases for visceral leishmaniasis and 20000 to were misdiagnosed as P. falciparum-positive by 30000 for cutaneous leishmaniasis. Treatment smear microscopy. and diagnostic tools are inadequate for Malaria and Leishmaniasis control and/or elimination. A Knowledge, Attitude, Practice (KAP) study as Moreover, as vector born diseases, their part of 3 years of follow up showed that, proper knowledge about visceral leishmaniasis (VL) in a environmental changes. Thus, definition of the rural community can be improved substantially environmental determinants, risk areas and the by community interventions. And VL patients population at risk, forms the basis for efficient and relatives can act as successful health use of scarce resources, and monitoring of agents if properly informed Using (GIS/RS control programs. Availability of tools for proper diagnosis, monitoring of drug efficacy and understanding mechanism of drug resistance We have made the risk map of cutaneous form the cornerstones for early and rapid leishmaniasis and identified risk areas and diagnosis and treatment not only to reduce their population at risk for use by the control program burden but also to contribute to their eventual control and/or elimination. The themes of completed and/or on-going projects of our team have been: genetic diversity, drug efficacy and determinants of visceral leishmaniasis in Kafta resistance in Plasmodium spp., host genetics Humera, one of the most affected areas in and drug resistance in Plasmodium spp., Ethiopia to aid planning of more focused control ecology of Plasmodium spp. infection, innate immunity in leishmaniasis, assessment of Fund raising/grant proposal
disease/infection risk factors, assessment of the type and magnitude of malnutrition in school The team made five applications for funding and aged children, and evaluation of geographical two were granted (Table 2 for details of these information system (GIS) and remote sensing (RS)in the control of disease of public health proposals and their status). importance in Ethiopia. Professional services
 Working as the technical working group for the national Onchocerciasis elimination  Member of the national Neglected Tropical Disease task force Lists of ongoing projects
Innate Immunity in leishmaniasis,  identify innate immune Two PhD students: Visceral and cutaneous mechanisms targeted by Geremew Tasew and Leishmaniasis, German African Leishmania for evasion Menberework Chanyalew collaborative project  obtain new insights into the role of cellular mechanisms that link innate and adaptive immune responses Clinical and molecular assessment  determine possible CQ treatment of P. vivax chloroquine (CQ) failure during the standard 28 days  Sisay Getachew resistance and population genetic of in vivo follow-up test diversity in South Nations,  genotype the pre- and post- Nationalities and Peoples Regional treatment samples to discriminate true drug failures from re-infection and relapses  characterize P. vivax population genetic diversity and structure Ecology of Plasmodial infections in  explore the presence and selected regions of Oromia, Ethiopia: prevalence of K13 mutations Clonal diversity, prevalence of conferring Artemisinin resistance antimalarial drug resistance-conferring mutations & host genetic characterization Therapeutic Efficacy of Artemether-  Determine the efficacy of One PhD student, lumefantrine for the treatment of Artemether-lumefantrine in uncomplicated Plasmodium uncomplicated P. falciparum falciparum Malaria in South Ethiopia Understanding the dynamics and  systematically investigate the extent and dynamics of the asymptomatic malaria carriage in low "hidden" human reservoir, and moderate endemic settings in asymptomatic submicroscopic Ethiopia – are they challenges for carriers of malaria infection, in malaria elimination? school children in Ethiopia and ultimately infer their infectiousness New projects submitted for funding
Rapid assessment of Visceral  33, 440.00 birr is transferred leishmaniasis in Dangur district, Benishangul Gumuz Health Extension Workers in  The project sites should be Ethiopia - Key to improve active chosen where prevalence is leprosy case detection and  it should involve already available system in MoH and regional health bureaus  sustainability, local resources, partnership should be defined Identifying Socio-Economic,  good background Cultural and Environmental Factors determining the risk to  collaboration with other leprosy in Oromia-Ethiopia stakeholders such as regional health bureau and MoH are in need Asymptomatic visceral leishmaniasis, and visceral leishmaniasis control in Ethiopia Lipid Bodies; can they be  69, 769 birr from AHRI-Core Biomarkers for improved Diagnosis of Disease and Better Patient Management? The impact of frequent mass  Partners identified and Proposal on development neglected tropical disease on the control of the vector; mosquitoes. Conferences, workshops and Training
Conference/workshop/training title
Lemu Golassa
Wellcome Trust Sanger Institute Genomic Epidemiology of Malaria (GEM-2014) Cambridge, Hinxton UK Sisay Getachew
Darwin, Australia Molecular Laboratory Techniques in malaria parasites Seleshi Kebede
New Orleans, USA Teshome Tsegaw
Bahir Dar, Ethiopia DNDI, Visceral leishmaniasis in east Africa Ahmed Seid
Lensa Aberra

Computer Modeling Training Adugna Abera
Adama , Ethiopia Neglected Tropical Disease Managers Training Lensa Aberra
Adugna Abera
Molecular Biology of Leishmania Leprosy Team
The Armauer Hansen Research Institute (AHRI) has established the leprosy research team in 2006to lead, plan and coordinate research activities on leprosy. In Ethiopia, it became possible to treat leprosy with a multidrug therapy (MDT) starting from 1982. Although appropriate treatment during the early stages of the disease reduces its progression and spread, poor diagnostics and lack of access to regular health care often mean that many who develop leprosy are treated late in the disease, after disfigurement. As a result of this the incidence of leprosy remains steady as studies conducted in disease endemic countries reported. In spite of the therapeutic success achieved with MDT to cure leprosy patients, still more work is needed to significantly decrease the current new case detection rate. For this reason, AHRI is currently working on the development of new and improved diagnostic tests, investigating the transmission aspect of leprosy to develop new and improved intervention strategies to curb the transmission of leprosy within the community, the immunopathology of leprosy, genetic susceptibility in leprosy and has also launched working on mapping hot spot leprosy areas in Ethiopia alongside with other priority research areas to generate evidence based findings which can be transformed into practice to improve the existing leprosy control strategies. Team Members
Dr. Demissew Beyene Daniel Taye, PhD candidate Mrs Kidist Bobosha, PhD candidate Yonas Bekele, PhD candidate Dr. Markos Abebe, Postdoctoral Scientist and TB Tadeye Abeje, Researcher team coordinator Etsehywet Gedlu, MPH student, completed Mrs. Martha Zewdie, PhD candidate Saba M. Lambert (MD, PhD) Edessa Negera, PhD candidate Nigussie Seboka, MSc student, completed (27%), clinical nurses with diploma (66%) and Research projects:
health assistants (2.8%). The median age of the respondents comprised 45% of the participants. Overall, Assessment of the Performance of general knowledge of leprosy and practice standard of the health workers in leprosy control activities respondents was found to be poor while attitude towards leprosy was positive for the majority of the at public health facilities, in Amhara and respondents. The results showed that 519 (86.3%) Oromiya regions, Ethiopia had poor knowledge. Overall 241 (40%) of the respondents had positive attitude towards leprosy while 205 (34.1%) had intermediate (mixed) attitude PI: Tadeye Abeje and Dr. Eshetu Kebede
and 155 (25.8%) had negative attitude to the disease. Among 83 respondents assessed for Project Summary: The aim of this project was to
diagnosis of leprosy only 15 (18%) diagnosed assess the overall performance of general health leprosy correctly. Variation in knowledge and care workers at public health facilities concerning attitude indicated a significant difference (p<0.05) activities related to the prevention and control of among different health institutions, professions, leprosy. Data was collected by self-administered gender, in-service training and years of experience. questions using structured questionnaires and The current findings underlscore that although observation of health workers' performance using a leprosy control activities are integrated to the checklist. This was supplemented by review of the general health services in the country, knowledge medical records and activity reports. A total of 601 and skill of leprosy diagnosis, treatment and general health workers responsible for leprosy control activities at public health facilities were unsatisfactory. Hence, attention should be given to included in a knowledge and attitude assessment develop training strategies that can improve health and 83 of them were subjected to practical worker knowledge and promote better leprosy evaluation, with on-site observation of how they management at public health facilities. This could handled leprosy patients. These included doctors be achieved through pre-service and in-service (MD) (4%), health officers and nurses with BSc training giving adequate emphasis to leprosy related practical work and continuous follow up. The manuscript reporting these findings is in Immuno-pathology Funding: AHRI core budget. Collaborating
Nodusoma Leprosoma Institute: ALERT training center.
PI: Edessa Negera
Haptogloblin gene polymorphism amongst patients with leprosy in Ethiopia Project summary: This project is the PhD
research project of Edessa Negera who has
PI: NigussieSeboka
registered at the London School of Hygiene and Tropical Medicine and is supervised by Professor Diana Lockwood. In leprosy there are two types of Project summary: This project is the MSc thesis
reactions; type I or reversal reactions and type II or research of Nigussie Seboka from the Department Erythema Nodosum Leprosum (ENL). Type II of Biology, Addis Ababa University. The aim of this reactions are inflammatory episodes that occur in study was to assess the haptoglobin (Hp) gene 20-30% of leprosy patients anytime in the disease allele frequency relationships with leprosy disease process, before, during or after treatment, and among patients rom ALERT referral hospital here in management of these complications is challenging. Addis Ababa, Ethiopia. A better understanding of the immunopathogensis of ENL may lead to improved clinical management Previous studies have suggested that some of these complications. In particular, this project is haptoglobin alleles are overexpressed in leprosy. focused on T regulatory cells--which normally down The mechanism for this remains to be clarified but regulate immune responses-- and whether aberrant may relate to the fact that habtoglobin-hemoglobin expression of these cells may contribute to complexes bind to surface CD163 on monocytes immunopathology. A total of 70 patients have been and macrophages, and may induce such cells into enrolled (42 with ENL and 28 with lepromatous an anti-inflammatory state. This may promote leprosy (LL) without reaction), and 64 and 56 of hemoglobin-haptoglobin these patients, respectively returned for additional ultimately provided greater heme iron needed for follow-ups. Blood and punch biopsies were taken M.leprae survival, while simultaneous suppressing from each individual at each time point. Flow an appropriate inflammatory responses needed to cytometry data analysis has been done for all eradicate M.leprae. Further studies have revealed recruited patients to characterize regulatory T cells important anti-oxidant functions of Hb as well. The and other lymphocyte subsets. In addition, to severity of multiple disease states, including HIV, evaluate antigen specific cytokine responses, 54 TB and leprosy infections have been associated PBMC samples have been stimulated with with haptoglobin genotypes, in particular genotype irradiated M. leprae and the supernatants have 2-2. In the present investigation we sought to been collected and to be assayed for cytokine confirm genetic associations between leprosy and content by ELISA. To measure the functionality of haptogloin as a first step towards probing this regulatory T cells, 54 samples have been sorted mechanism further. We observed that phenotype 1- using antibody coated magnetic beads into CD25+ 2 was under-expressed in leprosy (76%) compared (Treg enriched) and CD25- (Treg depleted) with control (92%), while phenotype 2-2 was overexpressed in leprosy (17.5%) compared with unfractionated PBMC stimulated in vitro. Data is control (3.1%) in a cohort of 109 leprosy patients currently under analysis. Funding: London School
and 108 controls. In contrast to these findings, no of Hygiene and Tropical medicine. Collaborating
associations were found between leprosy and ABO Institute: London School of Hygiene and Tropical
blood types. These findings, in particular the overexpression of phenotype 2-2, is compatible with previous findings observed in other countries Detection of new leprosy cases and (India) and further justified additional research into role of haptoglobin in susceptibility to leprosy. The household contacts at risk of developing project is completed and the student defended his leprosy by active case detection in Kokosa Woreda, West Arsi zone, Oromia region Funding: AHRI core budget. Collaborating
: Addis Ababa University
PI: TsehayneshLema
Project Summary: This project is the PhD
research project of Tsehaynesh Lema who is
pursuing her PhD training at Addis Ababa
University, Faculty of Medicine, Department of Assessment of prevalence of leprosy Microbiology. A remarkable decrease on the prevalence of leprosy has been observed after 1983 with the introduction of multidrug therapy associated factors (MDT) to treat leprosy patients in Ethiopia. In spite of this drop in prevalence, the yearly notification PI: Etsegenet Gedlu
rate and new cases in children remain remarkably stable, suggesting that there is no reduction in the incidence or transmission of leprosy in Ethiopia. Project Summary: This is the MSc thesis
Several regions in the country have been identified research project of Etsegenet Gedlu, an ALERT with higher incidence rates of leprosy. The goal of staff and a student at Addis continental institute of this study is to identify new cases in these regions public health in a joint program with Mekelle and trace household contacts at risk of developing University. The objective of the study was to leprosy by active case detection and mapping the retrospectively assess the prevalence of leprosy distribution of leprosy and assess health care reaction in leprosy patients and associated factors facilities delivery status and outcome of leprosy in ALERT Centre from September 2010 to August treatment in Kokosa Woreda, West Arsi zone, 2013. A total of 900 patient cards were selected Oromia region, Ethiopia. The project proposal has using systematic random sampling and reviewed. already obtained ethical approval from AAERC and Among the 900 cases, 22.4% had pauci-bacillary and 77.6% had multi-bacillary leprosy. More than (NRERC) and the project half, 54.1%, had grade 1 disability at diagnosis of will soon start. Funding: GLRA and AHRI core
leprosy whereas 18.4% had grade 2 disability at budget. Collaborating Institutes: ALERT, GLRA
time of leprosy diagnosis. and Oromia regional health bureau The magnitude of "ever having reaction in leprosy" was52.9% (476), whereas 44.5% (400) of them had the reaction at the time of diagnosis. Among those Discriminatory Discourses and the in reaction, 68.5% (326) had reversal reaction (RR) ingrained Social Constructs and 31.5% (150) had erythema nodosum leprosum (ENL). Higher numbers of reversal reaction (38.3%) PI: Daniel Taye, College of Humanities, Languages
and ENL (44%) were seen in those between 18-30 years of age. Both types of reactions were high among multi-bacillary leprosy cases with reversal Department of Foreign Language and Literature, reaction (71.8%) and ENL (98.6%). Interestingly Addis Ababa, University. 69.5% of the patients with RR had a bacillary index of 0 whereas 63.8% with ENL had bacillary index of Project Summary:
Discrimination related to disability among RR was 57.3% whereas that among ENL was 51%.; 19.6% of RR disease and disabilities are common in Ethiopia. patients had grade 2 disability, while 13.6% of ENL People use various types of discourse to identify patients had such a disabiliy.72% of patients with victims of diseases. The purpose of this study is to RR, and 68% of ENL developed reaction before critically examine discriminatory discourses and starting MDT.55.5% (181) of the patients with their underpinning (ingrained) social attitudes by reversal reaction and 49.3% (74) with ENL had co- healthy people against those affected by leprosy infections during the month preceding diagnosis and vice-versa. Two sites, Addis Ababa and with reaction. Co- infections examined included Kuyara have been selected to undertake the those of the urinary tract, gastrointestinal track. research. More than 40 participants from health upper respiratory tract, and oral cavity. The study is caregivers (6), religious persons (6), leprosy completed and the student has defended her sufferers and their families (19) as well as people thesis. Funding: AHRI core budget. Collaborating
living in the adjacent areas who have experience Institute: Addis continental institute of public
about discourse and text of leprosy discrimination (9) have been contacted as informants. A qualitative case study research design involving in depth interview was employed to draw data from two groups of people, the leprosy affected group and the healthy counterpart. Social and linguistics  FMOH, Ethiopia, theories such as Critical Discourse Analysis (CDA), Systemic Functional Linguistics (SFL) and social constructionist theories are the main paradigms  GLRA, Ethiopia used to conduct the case study.  ALERT hospital and Training centre

 Jimma University ENAPAL on December 18, 2014 to  Wello University inaugurate a book entitled "the pleasing  Prof. Diana lockwood, London School of unspoken voice" and had a discussion Hygiene and Tropical medicine, London, among partners in how to involve leprosy affected people and families in poverty  Dr. Christa Kassang: GLRA, Germany reduction in Ethiopia.  Dr. Linda Adams: HRSA, USA  Fund Raising  Prof. Gisela Bretzel, Germany  Risk Factors for Contracting Buruli Ulcer  Dr. Annemiek Geluk: LUMC Approach. It is a project initiated in collaboration with two German Universities Meetings
and research institutes in Ghana and Togo. The project proposal is submitted for  The DFG project (Risk Factors for funding to DFG. It is also in the process of Contracting Buruli Ulcer and Leprosy Two ethical review locally. Jimma University and Diseases – One Approach) preparation GLRA, Ethiopia are also partners in this meeting was held in Munich, Germany from 16-18 July, 2014. Kidist (AHRI) and Dr.  International collaboration for translation of Tesfaye (Jimma University) participated in Mycobacterium leprae molecular viability assay (MVA) to the clinical setting and  The Expert Meeting on "Developing application of MVA to a chemoprophylaxis- strategies to block the transmission of of-contacts model. This is a project leprosy" was held in Texas Medical Center, submitted to LRI by Dr. Linda Adams from Baylor Medical College, and Houston from National Hansen's Disease Programs, LA, 28 May – 2 June. Dr. Abraham Aseffa from USA in collaboration with AHRI and MRL AHRI has participated in the meeting. (Nepal). The project proposal is approved  Annual country learning events on leprosy for funding. This project has a training part activities from Nov 3 to Nov 6, 2014 where one team member will get training organized by TLMiE. Tsehaynesh Lema (a on M. leprae viability assay and the staff and PhD student) participated in the technique will be established at AHRI.  A team member (Daniel Taye, PhD student) attended a meeting organized by Leprosy Research Team on duty The HIV team and other viral infections are embraced. The team was re-established again early this year with aim of engaging researchers working in the area of HIV research and other viral and sexually transmitted and diseases (STD). Since ALERT Hospital is one of the centers that provide clinical care and services for infectious diseases such as HIV and STD, the Team has envisaged its research activities by engaging physicians working in the Hospital. Currently, the team is active in supervising MSc and PhD students, who are actively working on HIV, STD and other viral diseases of public health importance. Students receive direct scientific and technical supervision from the team. In addition to its scientific structure, the team also organized itself in such a way that other technical expertise are structured for administrative feasibility by the Institute. Team Members
percentages, 1.9%, 28.1%, 36%, and 0.83%, respectively, were observed in the Shebe town. Some factors such as religion, marital status, Although the team informally accommodates any previous history of genital ulcer and other sexually volunteer as a member who works at AHRI/ALERT, transmitted infections were found to be associated the Team currently consists of 1 senior scientist with HIV infection, whereas factors such as age, (Dr. Rawleigh Howe), 2 post-doctoral scientists (Dr. gender, job types, employment status, and amount Adane Mihret and Dr. Liya Wassie,), and other of income were associated with HSV-2 and HBV researchers and technicians (Yonas Bekele, infections. The data suggest that hot spot road side Tadeye Abeje, and Kassu Alemayehu) as active towns in rural Ethiopia continue to exhibit high members. In addition, PhD and MSc students who transmission of viral STDs, implying a need to work on HIV and other viral diseases are also strengthen disease control strategies through included as members of the Team. provision of better education, job opportunities especially for women, and expansion of childhood Completed Projects
vaccination, particularly for HBV. Sero-epidemiologic survey for HIV and proliferative and cytolytic CD8 T-cells response in elite controllers and long term (PI: Tadeye Abeje)
non-progressors in Addis Ababa, Ethiopia Road side towns in rural Ethiopia are a potential (PI: Melat Tsegaye; AHRI mentor: Dr.
sources of spread of HIV in rural communities. In a previous study 10 years ago, we compared HIV Rawleigh Howe)
and other STD prevalence rates in Shebe, a town outside large city of Jimma with Gundo Meskle, a Current vaccine strategies for protection against town in the isolated Derra region. The latter had a HIV infection are focused on comparisons of much higher prevalence of these STD, and cohorts with or without disease progression. A highlighted that road side towns in remote areas small percentage of individuals (1%), so called should be areas of focus for improved prevention of "Elite Control ers (ECs)", are able to contain the STD. In the present study, we conducted a virus without progressing to AIDS. One of the community survey to reassess the prevalence of immune system features exhibited by elite these STD in these areas. The study design was controllers in comparison with those with more cross-sectional. Blood was collected from a total of rapid disease progression is the presence of high 974 participants (492 from Gundo Meskel and 482 frequencies HIV specific polyfunctional CD8+ T- from Shebe town), aged between 15 and 49 years. cells. These cells display properties of both All blood samples were screened for antibodies to conventional CD8 CTL as well as CD4 helper T HIV-1, Herpes Simplex Virus-2 (HSV-2), and cells, as assessed by multiparameter flow Hepatitis B Virus core antigen (HBc), and for cytometry. The current study was under taken to confirm and extend previous findings by evaluating prevalence of HIV, HSV-2, anti-HBc (history of HIV gag peptide specific IFN-γ, IL-2 and TNF-α and HBV infection),and HBsAg (chronic hepatitis B virus de novo synthesized CD107a and perforin, infection)in Gundo Meskel town were 13.8%, 47%, products associated with granules of cytolytic CD8 56% and 5.3%, respectively, whereas much lower T cells. In addition, the proliferative state of HIV specific and non-specific CD8+ T-cells by the Karolinska
marker Ki-67 was assessed. We confirmed that mentor: Prof Francesca Chiodi)
polyfunctional T cells, as defined by the aforementioned cytokines and granule associated proteins, were indeed associated (p < 0.05) with HBV infection among HIV-1 seropositive patients is elite controllers but the association was modest, an underappreciated problem, particularly in the suggesting other mechanisms in addition to anti-retroviral therapy (ART) era; the public health polyfunctionality burden of complications of HBV are predicted to ultimately surpass the morbidity and mortality of frequencies of cytokine and granule producing CD8 tuberculosis. Although there are immediate effects T cells was independent of their proliferative status of chronic HBV infection in HIV-1 seropositive ex vivo, regardless of the HIV cohort, implying that patients contributing to toxicity of ART, the long most of the ongoing proliferation of CD8 T cells in term complications are severe and include HIV patients was unrelated to HIV specific secondary to liver cirrhosis, and hepatocellular carcinoma. The high prevalence of HBV infection in Ethiopia and other sub-Saharan African countries Ongoing PhD and MSc projects
underscores the importance of the HBV vaccine. However, this and other vaccines are known to Role of HLA polymorphism in driving HIV elicit suboptimal immune responses in HIV patients, clearing indicating that either improved vaccination scheduling or more efficacious vaccines are progression in HIV infected individuals in four hospitals in Addis Ababa, Ethiopia documenting HBV vaccine responses among HIV patients have been in adults; few have been (PI: Melaku Adal; AHRI mentor: Dr.
performed in children. The overall aim of this study is to evaluate serological responses to HBV Rawleigh Howe, AHRI and technical
vaccine in HIV positive and negative children, aged assistants: Kassu Alemayehu)
between 4 and 8 years who have no prior exposure to HBV vaccine or infection and further assess the This PhD project is a 4 year collaborative study functional and phenotypic properties of memory B between Oxford University, London and AHRI. The cells to HBV vaccine. The study is a collaborative overall aim of this study is to assess the impact of study between Karolinska Institute (KI), Sweden, host HLA polymorphisms during progression of HIV AHRI, and the pediatric department of ALERT disease. Gag, nef and pol genes of HIV isolated hospital and other selected health centers in Addis from HIV positive individuals prior to therapy will be Ababa. Funded by the Karolinska Institutet and sequenced and compared with high resolution HLA Swedish Medical Research Council, and AHRI core typing to identify putative HIV escape gene mutations associated with distinct HLA allelic polymorphisms within the peptide binding pocket. In parallel, peptides corresponding to candidate gene regions of interest will be assessed for CD8 T cell vaccine in HIV-1 infected infants in Addis stimulatory properties in vitro. Thus far, about 600 blood specimens have been collected from several local hospitals from Addis Ababa. DNA is currently being extracted from these samples, sequencing of (PI: Temesgen (MSc student); AHRI
proviral DNA will be performed shortly at Oxford mentors: Yonas Bekele, Dr. Rawleigh Howe
University, followed by HLA typing in collaboration and Dr. Abraham Aseffa; Karolinska
with the University of Oklahoma, U.S. Funded by Institute mentor: Prof Francesca Chiodi)
AHRI and the University of Oxford. Diarrheal diseases are a major cause of Immunological Response to HBV Vaccine morbidity and mortality worldwide especially in HIV- in Children: The Impact of HIV infection in 1 infected children in Africa. Rotavirus is the vaccine response in Addis Ababa, recognized as a common cause of severe diarrheal disease in infants and young children, though the disease burden can be significantly reduced by vaccination. However, impaired responses to (PI: Desalegn, MSc student; AHRI mentors:
childhood vaccinations have been reported in HIV- Yonas Bekele, Dr. Rawleigh Howe and Dr.
1-infected children despite successful antiretroviral therapy. The aim of the current study is to assess the antibody response at 1, 6 and 12 months after Assessment of peripheral  T cells: rotavirus vaccination in HIV positive and negative phenotypic and functional heterogeneity in infants, to compare the rotavirus vaccine efficacy with that of other childhood vaccines (measles, singly and dually infected HIV-TB patients HBV) previously studied in HIV positive infants, and in Addis Ababa, Ethiopia to assess the cell surface expression of molecules involved in B cell survival and apoptosis in HIV positive and HIV negative infants both pre and post (PI: Mikias Negash (MSc); AHRI mentors:
rotavirus vaccination. The stud cross-sectional Dr. Rawleigh Howe and Dr. Liya Wassie)
study will recruit HIV+ and HIV- infants who were vaccinated within the preceding year from the γδ T cell populations comprises minor subsets pediatric department of ALERT hospital and (<5%) of the circulating CD3+ T- lymphocytes, selected health centers in Addis Ababa, and Patient However, an increase in relative and absolute number of γδ T cells have been described in collaborative study between Karolinska Institute peripheral blood of HIV-1 seropositive individuals (KI), Sweden and AHRI; funded by KI and Swedish as well as in HIV patients co-infected with Medical Research Council, and AHRI core funds. Different studies indicated the increase in γδ T cells in HIV patients Analysis of co-receptors and innate is mainly attributed by Vδ1 expressing cel s which immune markers in HESNs are not thought to be expanded in response to HIV antigens; rather they may be redistributed from mucosal (PI: Markos Negash (MSc student), AHRI
expressing cells in healthy individuals are found to mentor: Dr. Liya Wassie)
be quantitatively and qualitatively defective in HIV-1 infected patients, though there are discrepancies in Serodiscordance of HIV is a phenomenon that the literature concerning this subset among occurs in a minority of HIV exposed individuals, HIV/Mtb co-infected patients. This study is aimed to analyze the profile of γδ T cells and expression of wherein one ART naïve partner is HIV positive and activation (CD38), proliferation (Ki67), adhesion (αE unprotected sex. Although a number of genetic and -CAM), exhaustion and apoptotic immunological factors have been assessed to markers (PD1, CD95) and cytokine production in explore the mechanism of resistance, few studies HIV positive patients with and without Mtb disease have probed the potential role of innate immunity of in a cross sectional design TB patients without HIV, the HIV negative partner. In this study, we and age and sex matched healthy individuals will hypothesize that expression and function of innate be used as control groups. This proposed study immune cell markers, in particular TLR7, known to has been delayed due to procurement issues. Like be an innate receptor for HIV, protective alleles of the above studies, this project is also funded by KIR gene products on the surface of NK cells, as AHRI core budget. well as NK lytic function, are significant factors contributing Seroprevalence of cytomegaloViruse and seronegative individuals, after controlling for viral Hepatitis E Virus among Pregnant Women load among HIV positive partners. The study design in Ghandi Memorial and Yekatit 12 serodiscordant couples and apparently healthy hospitals, Addis Ababa, Ethiopia individuals and aimed to compare the expression immune markers using RT-PCR and ELISPOT techniques. Thus far, sample collection from (PI: Meseret Abebe, AHRI mentors: Dr.
participants has been completed, and shortly Adane Mihret, Dr. Abraham Aseffa and Dr.
further laboratory analyses are planned. The study Rawleigh Howe)
is funded by AHRI core budget. CMV and Hepatitis E infection during pregnancy are major infectious causes of morbidity and mortalitiy for women or their newborn infants. To date, there have been few studies to define the scope of this problem within Ethiopia. The present MSc thesis project is a collaborative study between AHRI and ALERT, to define to determine the seroprevalence of CMV and HEV among pregnant mothers. The study has already obtained ethical approval and currently blood samples have been the burden and viral etiology of chronic hepatitis, collected from 395 pregnant women and serum stored at -20°C until further assayed for IgG and hospitalized patients, as well as the seroprevalence IgM antibodies to these pathogens by ELISA. The of Hepatitis E and its contribution to pregnancy- project is funded by AHRI core budget. related hepatitis. This project is planned for 3 years, and will involve multiple sites throughout Ethiopia. Other ongoing studies conducted
This project is funded by the Federal Ministry of Health. by the team
Hepatitis B surface antigen (HBsAg) and pandemic influenza: prospects for cellular women at Bishoftu and Tirunesh Beijing hospitals, Ethiopia Project summary: This study is a collaborative
project between the Norwegian Institute of Public
Health (NIPH) in Norway and AHRI to investigate
(PI: Zelalem Desalegn from Addis Ababa
the prevalence of past pneumococcal and influenza Science and Technology University, Mentors
infections in children and further determine if from AHRI: Dr. Liya Wassie and Dr. Adane
immunity to influenza decreases the likelihood of contracting secondary bacterial pneumonia. The team further plans to test the hypothesis that influenza is a major risk factor for childhood Project summary: This study has been proposed
pneumonia. The study involves apparently health by one of the faculty members from the Addis children residing in different sections of Addis Ababa Science and Technology University, who Ababa whoe will be followed up over a period of has received funding from his University as part of one year. To date, 107 children have been thematic research to conduct the study. The study recruited and optimization of experimental analyses will be conducted at Bishoftu and Tirunesh Beijing (IFN-ELISPOT, hospitals, located in the vicinity of the University Immunoassy to measure influenza-specific immune responses) is currently underway. This study is with the objective to assess the prevalence of proposed for 3 years (2013-2016) and funded by hepatitis B surface antigens (HBsAg) and identify attending the two hospitals between June and Other networking activities,
transported to AHRI lab and further tested for collaborations and travels
HBsAg. Currently, recruitment of study participants is completed and experimental analyses are Few members from the team act as local contact points in the East Africa Consortium for Clinical Research (EACCR), particularly for HIV node Hepatitits and chronic liver disease activities of the Ethiopian sister institutions (Butajira Hospital and Bole Health Centre). The consortium research project is a multi-country project involving countries of the east Africa including Tanzania, Sudan, Uganda, Hepatitis and chronic liver disease research
Kenya and Ethiopia. The consortium assists sister project (Project leaders: Dr. Rawleigh Howe
institutions in terms of building capacity (short-term and Dr. Adane Mihret together with FMoH,
training and upgrading infrastructure facilities) for Ethiopia)
future possible clinical trial facilities. This year, the team provided technical assistance and donated Project summary: This project has been initiated
with the Federal Ministry of Health, Ethiopia laboratory facilities to the sister institutions (FMoH) and AHRI to assess the overall burden of hepatitis in Ethiopia. This includes serological and clinical efficacy of hepatitis B vaccination in the In addition, in the context of proposed and ongoing country, the seroprevalence of hepatitis C and D, PhD projects, the team established links with several overseas universities and institutions, Purpose: To setup establishment of a national including Oxford University (UK), Norwegian referral lab for Hepatitis in Ethiopia along with other Institute of Public Health (NIPH, Norwary) and partners in the Country including EPHI and ALIPB Karolinska Institute (Sweden). Purpose: As part of his PhD training program, he Like the previous year, this year some of the team has been attached to the KI in Sweden members also participated in national and international meetings and training activities that Markos Abebe (September 15-18, 2014, Bahir Dar, both helped upgrade skills and allow to network with experts in specific fields of expertise: Purpose: Research dissemination workshop on HIV Kassu Alemayehu and Meseret Abebe (Sept 1-4 Yonas Bekele (September – December, 2014; KI, Sweden) Clinical Trial Team
With the mission to generate clinical evidence for new drugs, vaccines, and treatment regimens against major infectious diseases, AHRI has been increasing capacity building activities in the area of interventional clinical trials since 2001. Currently, three clinical trials involving drugs and vaccines are in progress. In parallel, the team has continued building capacity by establishing a clinical study ward for the conduct of bioequivalence studies and a standard clinical laboratory facility. Research highlights: Bioequivalence Clinical Centre at AHRI
Bioequivalence Clinical Centre at AHRI (PI:
excellence in the Eastern African region and Mekonnen Teferi) beyond for the conduct of BE studies in compliance with international standards. A generic drug is a drug product which is comparable to a reference (brand) drug product in The clinical centre at AHRI in collaboration with the dosage form, strength, route of administration, regional Bioequivalence Centre (RBEC), has quality, performance characteristics, and intended conducted the first ever bioequivalence (BE) clinical use. However, it can differ in color, shape, taste, inactive ingredients, preservatives and packaging. ciprofloxacin in comparison to an innovator Bioequivalence (BE) studies hence can verify the production. This initial study conducted to verify quality of generic products before being widely whether or not the established system in AHRI and marketed and it becomes a requirement by RBEC is able to conduct studies according to regulatory bodies for licensure. Currently, generic international requirements and guidelines. In drugs have a stake of more than 65% in the world's addition, it aimed to accumulate data for planned pharmaceutical market. The use of generic drugs is WHO inspection for possible certification of the expected to grow over the next few years as a clinical site and analytical laboratory at RBEC by number of popular drugs come off patent as well as characterising the bioavailability of the test product for cost reason primarily in developing countries. In (Strox of Universal Cooperation) in comparison to parallel, pharmaceutical industries that produce generic drugs are flourishing in East African region HealthCare Pharmaceuticals Inc.). including in Ethiopia. These companies are primarily targeting essential drugs such as A single dose, randomised, open-label, two- antibiotics, anti-retroviral, and antimalarials among treatment, two-period, two-sequence crossover others. Ensuring the quality and safety of such study was conducted on 12 healthy volunteers products is thus very essential. However, BE under fasting conditions at one study site. The relative bioavailability of ciprofloxacin for the test particularly in East Africa and in general to sub- product was calculated as 91.22% (Geom. mean) in comparison to the reference product at 90% CI establishment of a locally accessible and affordable and the finding was within the predetermined international standard BE testing centre would have acceptance range (i.e. 80% - 125%), for the extent paramount importance for ensuring safe, effective and rate of absorption. The single doses of the test and quality medicine to the public as well as for and reference products were well tolerated. promotion of investment in the pharmaceutical Therefore, this study serves as a milestone for industry in Ethiopia and Eastern African region. future studies and the data can be available for the planned WHO inspection and certification that The RBEC was recently established in Addis enables the centre to become competitive Ababa in the compound of School of Pharmacy, internationally. Funding Source: AHRI and RBEC. Addis Ababa University. The center has a scope of testing BE of generic drugs against innovator products in compliance with the standards set by WHO and plan to provide service to companies in East African region. AHRI was one of the key players that support the idea of establishing a bioequivalence centre in Ethiopia and in line with this it has established a phase one clinical centre for the conduct of BE studies. Therefore, the BE centre in Ethiopia aspires to become centre of Clinical Trial Laboratory becomes fully We conducted a double-blind randomized placebo controlled bridging trial to assess the safety and immunogenicity of the Shanchol oral cholera vaccine among 108 healthy adults (aged 18 years It is in this year that the clinical trial laboratory and above) and 108 children (aged 1 – 17 (CTL) starts its full function for clinical trial study years).Evaluation of anti-vibriocidal antibodies to subjects. Currently, the laboratory is fully engaged the O1 inaba serotype indicated that baseline titers in the screening of study subjects to assess were detectable in a significant fraction of recipients eligibility and safety before, during and after the and these baseline titers increased with increasing clinical studies. It is unquestionable that this will age. After vaccination, titers improved dramatically; improve the scientific standards of clinical trial this was most apparent in recipients above age 5, activities in AHRI. In Addition, this will minimize with resultant sero-conversion rates from 81-89% laboratory associated trial costs significantly. The and a 15-32 fold increase in geometric mean titers; laboratory is equipped with fully automated clinical those recipients below age 5 exhibited only 53% chemistry, hematology and electrolyte analyzers to sero-conversion, and a 4 fold increase in titers. In provide screening and other services for the clinical contrast to results with O1 inaba, seroconversion trial unit of the institute. The laboratory will also rates specific to O1 agawa were nearly constant continue striving to maintain the standard of service across all age groups ranging from 70-90%. Finally, by establishing a GCLP-compliant responses to the more severe strain of cholera internationally accredited facility. Therefore, we O139 were less pronounced but significantly higher would like to use this opportunity to announce our than baseline, and this was true independent of age readiness to work with partners in capacity building group. The vaccine was well tolerated and no and in the conduct of clinical trials using our lab adverse or serious events were reported within 3 days of dosing in any vaccine recipient. In sum, these results show that the responses to the Completed Research Activities
vaccine components in the Shanchol vaccine were strongin this clinical trial; younger children aged < 5 The First Bridging Trial in Africa did not respond as well to the O1 inaba as opposed to the O1 agawa component; and in general, Cholera remains a serious global challenge with responses to the O139 component were significant, disease burden estimated at over three million but less pronounced. Collectively, these results cases and more than 100,000 deaths throughout demonstrate the usefulness of Shanchol in this much of the developing world. In recent years, the setting. The manuscript of this study has been World Health Assembly has called for the submitted for publication to the Journal of American incorporation of oral cholera vaccines as part of an Society of Tropical Medicine and Hygiene. Funding
integrated, comprehensive strategy of cholera Source: International Vaccine Institute, South
prevention and control. Currently, two killed oral cholera vaccines (OCV) are prequalified by the World Health Organization (WHO). Both Dukoral™, Exploratory, phase II double blinded, randomized placebo controlled trial of recombinant cholera toxin B subunit (WC-rBS), and Shiunko ointment local application twice a Shanchol™, a bivalent whole cel vaccine without day for 4 weeks in Ethiopian patients with localized cutaneous leishmaniasis immunogenicity and efficacy in preventing cholera in endemic settings. The components of Shanchol PI: Dr Oumer Ahmed
include attenuated strains to the O1 serotypes (including serotypes O1 Inaba and O1 Ogawa), as Cutaneous leishmaniasis (CL) is a major tropical well as strain O139, a strain inducing a more skin disease which represents a worldwide public severe form of the disease, most common in South- health and social problem in several developing countries including Ethiopia. To deal with this, an exploratory phase II, comparative, double-blind, Previous studies have demonstrated that Vitamin D randomized, placebo-controlled, single-centre study has been carried out in Ethiopia. Clinical efficacy mucosal immune responses to infections whilst and safety of Shiunko ointment compared with placebo, when applied on the lesion twice a day for 4 weeks in a total of 40 patients (25 males and 15 inflammatory responses. The focus of the current females, aged 18-62 years) with localized solid CL study is 1) to evaluate the antiretroviral and immunomodulatory treatment naïve HIV infected patients, and 2 to A marked reduction in lesion size was observed on determine if anti-microbial treatment with vitD3/PBA week 16 of treatment in the group treated with can significantly shorten the duration of standard Shiunko compared with placebo (69 and 22% anti-TB therapy. The study is a randomized, reduction, respectively). The overall rate of lesion double-blinded, placebo-controlled, phase-II clinical reduction during the four weeks treatment period trial. TB patients < 5 days into standard was significantly faster in the Shiunko compared with placebo. Furthermore, Shiunko treatment chemotherapy and treatment naïve HIV patients provided significant therapeutic effects on wound are referred to the study team from health centres closure in patients with ulcerated lesions. The and hospitals in Addis Ababa. The goal is to recruit clinical efficacy and tolerability of Shiunko was 350 TB-infected and 200 HIV-infected patients. shown to be comparable to placebo with regard to Daily oral doses of vitD3/cholecalciferol (5000 its clinico-parasitological response (cure rate and IU/day) and PBA (1 gram/day) will be administered parasitological clearance).Further studies should be carried out to confirm its clinical efficacy in a larger during a treatment period of 4 months. Patients will number of patients with well-defined clinical signs receive supportive care and follow-up consultations and symptoms of CL, with longer treatment period 4, 8, 16 and 24 weeks after the baseline and follow-up, and with modification of the method assessment. A composite clinical TB score in TB of treatment application to improve drug penetration patients and HIV viral load, CD4/CD8 T cell counts, to the target site of action. Funding source: AHRI intestinal inflammation and barrier function in HIV core and the University of Nagasaki patients are used as primary outcome measures. Antimicrobial Immune reconstitution in tuberculosis and immunological correlates of clinical recovery in both HIV disease using antimicrobial treatment arms of the study. To date, both the TB and HIV with vitamin D and phenylbutyrate arm recruitment has been completed, and follow up is ongoing, with the last follow-up expected to be PI: Nebiat G. Gebreselassie in collaboration with
completed by June, 2015. The project is a Endale Kassa, and Wondwossen Amogne, Black collaboration with AHRI, Black Lion Hospital, Addis Lion Hospital, Addis Ababa, and Susanna Brighenti Ababa, School of Public Health, Addis Ababa, and from the Karolinska Institute Karolinska Institute. Funding source: the Karolinska Institute Marking the first BE study at AHRI Lab Technician taking blood sample from the fist GCP Training for Shuinko Trial Conducted at Ankober participant for Oral Cholera Vaccine Trial Field Travel to Haromya Menenjites Vaccine Trial site Initiatives
Zoonosis/One-Health Group
Operational Research  Generate a comprehensive baseline data base on the epidemiological dynamics and impacts of Projects: Two projects have been funded in 2014
human and animal disease problems in Ethiopian Somali Regional State (ESRS) ETHICOBOTS (Ethiopia Control of Bovine  Prioritize major human and animal health Tuberculosis Strategies) problems according to their projected magnitude and impacts in the region Identify and prioritize major constraints and 5 year consortium project, UK Government short coming of existing regional human and funded (around 3 million GBP) animal health services  Design and test health service methods and University (UK), AHRI, AAU, NAHDIC and EARI tools tailored to the realities and needs of ESRS (Ethiopia), Swiss TPH (CH) Evaluate the role of key cross cutting issues on Start Date: 01/09/2015 existing and proposed integrated health systems Aim: assess BTB prevalence in dairy farms as under the pastoral setting. These would include well as risk factors for disease transmission in participation, gender and youth representation, intervention and control strategies (socially and globalization and free trade, climate change, economically feasible).  Potential impact: reduce the high BTB burden in the dairy industry, reduce the zoonotic threat, Capacity building provide infrastructure for the control of other zoonosis. Rea Tschopp will coordinate WP6 (evaluation of Training of 10 MSc and 3-4 PhDs relevant control strategies) and advise on WP2  Trainings of regional health professionals.  Provide executive capacity building trainings to management of illness and health amongst poor relevant JJU and ESRS stakeholders on subjects related to development projects  Training of community representatives to create JOHI (Jijiga Pastoral One-Health Initiative) awareness on health systems, methods and tools  Establish and run well equipped integrated 12 year project, Swiss Government funded health database, diagnostic facilities and training (around 5 million USD) Main partners: Jijiga University, Swiss TPH and  Deliver adequate diagnostic, therapeutic and AHRI (tri-partite MoU) prophylactic inputs for research and outreach Start: inception phase 01/01/2015; full project service tasks included in the program  Rea Tschopp will be co-coordinating the project Service delivery with Jijiga University  Aim: The program will work on: Operational research, Capacity building and Extension  Design, test and implement community centred service targets aimed at enhancing health methods and tools for sustainable integrated services in the region thereby promoting food health surveillance and reporting system security and economic wellbeing of communities  Design and evaluate pilot packages for integrated preventive and curative health service (including trained integrated health teams, detailed program of operations, adequate tissue samples did not yield any Mycobacteria technical and logistic facilities, adequate supply of appropriate strain vaccines and other supplies, appropriate record keeping and reporting mechanism)  Design, evaluate and implement family planning, maternal and child health services tailored to the presentation on livestock productivity in Sellale realities of regional circumstances  Quarterly science group meeting SDC at the communication and dissemination of research  Jijiga workshop: 2-4 Sept 2014. Brainstorming and extension service outputs and lessons from workshop on JOHI one health program operations  Promote dissemination of information to raise workshop Sabetta (2-3 Dec 2014) public awareness on relevant human and animal  Advisor to Megdelawit Ayele on her DVM thesis "community perception on the role of dogs in the decline of the wolf population in the Bale BTB in non-human primates Mountains National Park". 15 Reviews for 11 journals (AJMR, VetIt, BMC, On-going project since 2012, funded by Born PloSOne, IJLP, BMRJ, JVMAH, JMLD, AJAR, Free Foundation (UK) JAERD, SciTechnol, JPHE); abstract review for 4 autopsies were carried out on non- human the IGAD Conference Dec 2014. primates belonging to the study. They were found dead. All showed extreme emaciation and multiple granulomas in the liver. Culture of Capacity Strengthening for
was included. Existing capacity was enhanced Operational Research (OR) in
through a competitive grant scheme providing TB researchers with financial and technical support. The Ethiopian Tuberculosis Research Advisory Committee was also supported in its functions. Regional ethics review bodies were strengthened instrumental for the enhancement of tuberculosis or established where they did not exist. Fifty-two (TB) control. In 2012, the Ethiopian Federal Ministry people were trained and conducted 13 OR projects, of Health launched an initiative for capacity building of which six have been published to date. In in operational research (OR) with the aim to addition, eight protocols were supported through develop capacity for OR in a multiyear initiative. grants. Ethics review bodies were strengthened in The initiative was developed in collaboration with all regions. The initiative trained participants from regional, national and international experts. Teams all regions and succeeded in the completion of all representing regions in Ethiopia conducted OR stages of the OR process. The success of the addressing national and regional priorities. To program can be attributed to the team approach, make use of local expertise and increase ‘learning while doing', integrated mentorship sustainability, a domestic mentor training program program and strong national ownership. supported by development of selected research AHRI-AAU Biomedical Science
leaders in universities to form a critical mass of Postgraduate Training
scientists. AHRI has a strong track record of Partnership Program (BSPP)
sciences for Addis Ababa University (AAU) by exposing them to its own and partner laboratories The dramatic expansion of postgraduate intake at at international Centers of Excellence and Addis Ababa University may compromise quality in supporting high quality research. biomedical research and training unless it is Thus the aim of the program is to strengthen biomedical science postgraduate training at Addis collaborating Swedish laboratories. AHRI will Ababa University through intensive training of provide laboratory access and thesis supervision as talented young scientists at the PhD level for well as project management. A committee of 6 leadership in research and higher education in members from AAH and AHRI was formed, and science at regional universities. Research support from 27 PhD applications, 10 candidates have been and training awards will be given to the best PhD students in medical microbiology, genetics and biotechnology registered at AAU. A bridging course The expectation is that this program will contribute in research leadership and laboratory training at to the development of a high quality post graduate AHRI and collaborative partner institutions in faculty for biomedical science training and research Sweden will be supported. Each PhD candidate will in the Universities, forge stronger links between conduct research over 4 years and concomitantly research and educational programs at AAU, AHRI, participate in training of Masters and undergraduate and Swedish universities. students. Upon graduation, the young scientist will be provided with a small grant to start his/her own As part of capacity building initiative the following research at the Department. The project will trainings have been provided to BSPP candidates additionally support sabbaticals for AAU professors [Research Ethics: 11-13 Nov, 2014 and GCP: 16- and short time training of postdoctoral scientists of Ethiopia-Emory TB Research
Training Program (EETB-RTP)
The main educational mechanism is high quality, Program (EETB-RTP) represents a partnership semester long, distance learning courses delivered between Emory University in Atlanta (USA) and by faculty at Emory University (Atlanta, USA) via three Ethiopian institutions in Addis Ababa real-time web-based videoconferencing as well as including AHRI, AAU, and the Ethiopian Public through intensive short courses carried out in Health Institute (EPHI), a national public health Ethiopia. A comprehensive mentoring program for institution that is part of the Ethiopian Federal trainees, which includes both Ethiopian and Ministry of Health. The EETB-RTP is focused on internationally based mentors, is also an important providing didactic and mentored TB research program component. From 21 applications, 8 training for promising Ethiopian investigators; the candidates (5 PhD, 2 postdoctoral researchers and goal is to provide either short or long term training 1MSC) were selected as a Fogarty fellow for this for MSc, PhD, and post-doctoral trainees and their program. Currently, the fellows have identified their institutions with the skills and capacity to carry out research topics, and are reviewing their research internationally relevant TB-related research (e.g., ideas and protocols in collaboration with mentors clinical and/or translational research, epidemiologic assigned both from Emory and Ethiopia. For the research, implementation science (operational coming period they are all expected to finalize their research), behavioural/social sciences research, research protocol and submit it to the Institutional and laboratory based research). The EETB-RTP is funded by a Global Infectious Diseases grant from the U.S. National Institutes of Health (NIH) Fogarty International Centre Current Fellows of the Ethiopia-Emory TB Research Training Program (EETB-RTP)
Muluwork Getahun Assistant Researcher Head, National TB reference Laboratory Addis Ababa University Lecturer, College of Medicine and Health Sciences , Hawassa University Addis Ababa University Assistant Professor, Microbiology, AAU Yohannes Gezahegn Addis Ababa University Lecturer, Social Anthropology, AAU Mulugeta Tsegaye Internist, HIV/AIDS, TB, STI Training Specialist Endalamaw Gadissa Postdoctoral Scientist Graduate Training
Training of students (Masters, PhD and summer interns) is one of the key missions of AHRI. Students
registered at different Ethiopian Universities are accepted annually to do their thesis work with the supervision of AHRI scientists. The tables below shows list of students that are working at AHRI towards their master's and PhD degree in 2013/2014. MSC students 2013
Current Status (June, 2014) Desaglegn Yibeltal The Effect of Antiretroviral Drugs o Ongoing (Sample collection) Immune Response to Hepatitis B Vaccine: The impact of HIV on Hepatitis B Vaccine Response in Children in Addis Ababa Ethiopia Feregenet Tesfaye Circulating Breast Cancer-associated MicroRNA Expression in Serum as Biomarker for Breast Cancer Detection The New Micro-culture Method(MCM) for Jimma University Ongoing (Thesis defense at the Diagnosis of Cutaneous Jimma university and Leishmaniasis in Ethiopia Publication in process) Mycobacterium tuberculosis specific Finished part of my thesis and functional immune response in pregnant ready for defense women with HIV and Latent Tuberculosis co-infection in Addis Ababa Ethiopia Analysis of CCRS and CXCR4 Receptor Gonder University Expression and Innate Immune Markers among Highly HIV Exposed Seronegative Individuals Living in North West Ethiopia Seroprevalence of cytomegalovirus and Sample collection and waiting for hepatitis e virus among pregnant women the purchase of the in Gandhi memorial and Yekatit 12 reagents(ELISA kits) hospitals, Addis Ababa, Ethiopia The role of γδ T cells heterogeneity in Ongoing (already have more than HIV-TB mono or dual infected patients in 90% of reagents needed) Addis Ababa, Ethiopia Comparison of apoptotic markers on Jimma University Finished all the lab work and writing macrophage and T cells in peripheral blood and Lymph node from TB patients and controls. Comparison of drug resistance between lineage seven and other lineages of Mycobacterium tuberculosis in Ethiopia Temesgen Ewunetu Immuniological response to rote Virus Gonder University vaccine among HIV 1 exposed infants in Addis Ababa, Ethiopia Epidemiology and Drug resistance pattern Thesis defended and working on of Mycobacterium remaining laboratory work tuberculosis in North West Ethiopia: Resource limited region. Optical Adjustment and Stage Automation of a Microscope and Automatic Detection of Mycobacterium Species from Sputum Smear Slides using Image Analysis Techniques Effect of Diabetes Mellitus on T-cell Jimma University Finalized 40% of samples immune response of Pulmonary Tuberculosis patients, Addis Ababa - Ethiopia PhD students 2014
Current Status
The role of Cattle in transmitting the Completing research work, writing causative agent of tuberculosis in two manuscripts and thesis, three Zones of Amhara region manuscripts are ready. Molecular Epidemiology and Drug Drug susceptibility testing results Resistance of Mycobacterium tuberculosis Among New Smear Positive Pulmonary Tuberculosis Cases in eastern Ethiopia Critical Analysis of Leprosy Data collection finalized Discriminatory Discourse and the Underpinning Social Constructs Determinants of MDR-TB in Eastern part Data collection is finalized and data of Ethiopia Dire Dawa entry is started The immunopathology of erythema Patient recruitment and sample nodosum leprosum Molecular epidemiology, drug resistance Secured grant and develop a pattern of M. tuberculosis and clinical research and training collaboration outcome evaluation in Woldiya region, Ethiopia Fekadu Desta Tona Immunophenotype and Functional Characterization of T Cell Subset and Monocyte-Macrophage Lineage cells within Lymph Node Granulomas and peripheral blood of calves Exposed to Natural Mycobacterium bovis Infection Innate Immunity in visceral leishmaniasis Data was analyzed and result was submitted to German's PI and collaborators Evaluation of M. leprae unique antigens Finalized the thesis compilation and for early detection of leprosy and cytokine submit for comments to the advisors profile of reactional patients. Ecology of Plasmodial infections in Data has been generated. selected regions of Oromia, Ethiopia: Clonal diversity, prevalence of antimalarial drug resistance-conferring mutations & host genetic characterization Analysis of immune response regulation Works underway include laboratory experiments, data analysis, and manuscript writing Role of HLA polymorphism in evolution of Secure funding of our project and HIV viral diversity in Ethiopia activities are on progress Innate Immunity in cutaneous 80% of Sample collection completed, 60% of lab work completed and 30% of data analysis done Molecular markers and mechanisms of T Efficacy of Artemether-lumefantrine and Two papers published, Manuscript in Chloroquine for the treatment of preparation stage and Remaining uncomplicated Malaria in Jimma Zone activity underway mainly the surroundings of Gilgel Gibe Hydroelectric power dam , southwest Ethiopia Assessing the prevalence of Plasmodium A 28 days In vivo efficacy study was vivaxchloroquine resistance by using in completed and the results of the vivo drug sensitivity test and molecular work were shared to Federal characterization of parasite isolates in Ministry of Health and World Wide South Nations and Nationalities Peoples Antimalarial Resistance networks, Regional State (SNNPR), Ethiopia and publications are underway. The remaining work is on progress. Discovering Podoconiosis Susceptability Sample data collected from Gojjam Genes: from molecular to disease control for a neglected tropical disease (NTD) Detection of new leprosy cases and Project proposal approved by AHRI- tracing of household contacts at risk of ALERT Ethical Review Board developing leprosy by active case (AAERC) and purchase of materials detection and assessment outcome of treatment in Kokosa Woreda, West Arsi zone, Oromia region: Clinical, molecular and immunological approach Tsighemariam Teklu Epidemiology of visceral leishmaniasis Waiting for test kits and VL/HIV coinfection in North Ethiopia Monocyte function in TB, HIV, TB/HIV co- Proposal approved by National infected patients Ethical Review Board (NERC) Wondossen Tsegaye Epidemiology of Streptococus Finalized the first phase sample pneumoniae nasopharyngeal carriage: Serotyping, molecular characterization and Antibiotic sensitivity pattern in Ethiopia Wubayehu Kahaliw Activity test, isolation and chemical Pharmaceuticals fund and supply structure elucidation of antituberculosis agency (pfsa) was communicated consitituents from plants used in and purchase of solvents was traditional medicine in Ethiopia permitted and the root of Carisa edulis and root bark of Vernonia Amygdalina was collected from Gondar town around Angereb River Bacterial Meningitis in Ethiopia: study of Finalized Ethical Clearance etiologies by use of real time PCR, Processes and PhD Research MLST and cytokine detection Project Sample collection Epidemiology of TB in South Ethiopia Reviewing the researching project proposal based on the comments from both AHRI and AAU Institutional Review Boards (IRBs) Immunological Response to HBV Vaccine The manuscript is under in Children: The Impact of HIV infection in the vaccine response in Addis Ababa, Ethiopia Postgraduate students completed their study in 2014
Date completed
Completed and in the process of writing Manuscript Nigussie Solomon MSc Defended but in the process of working on laboratory work Defended his Thesis Research Support
Data Management and
(Oromiya, Amhara, SNNP) region of the Biostatistics Unit
country in Health Centres and Hospitals. • Surveillance of Bacterial Meningitis in Ethiopia: Double data entry done for AHRI Data Management unit has been supported Hawassa patients (33 ) , Gondar Patient () by a team of dedicated data management staff who and Black-lion patient()data and filed have worked tirelessly to establish good and • Assessment of prevalence of leprosy implemented procedures for questionnaire or CRF and database design, double data entry with good associated factors: a retrospective study in verification and validation, data analysis, good All African Leprosy, Tuberculosis and back-up, filing and archiving system all of which Rehabilitation Training Center (ALERT Center) Addis Ababa, Ethiopia (Esegenet confidentiality of the unit's and col aborator's data. Gedlu, MPH program): 900 patients' CRFs double data entered, analysed and filled. Mission and Goal • Comparison of Drug Resistance between Lineage Seven and Other Lineages of The mission of the unit is to contribute quality Mycobacterium tuberculosis in Ethiopia data management and statistical analysis for (Shiferaw Bekele, MSC program): data researchers and students. entry done for a lot of leprosy cases and The Goal is to provide close to 100% satisfaction for health researchers / students by • Malaria project( Sisay, PhD program) : 225 providing quality data and report at the end of data Done double data entry the Ethiopian year to help policy makers. • Characterization Susceptible Patterns of Blood culture Project Title and Work Done Isolation from Septicemic Patients(CASP) at St Paul Hospital: 555Done double data • STREAM project: AHRI and St. Peter's
Hospital: lots of Patients' CRFs data double • PCV10 vaccine (Dr Wondewosen entered; entry, queries and verification on- Tsegaye, PhD) : 786 data double entered going. : Data filed: 170 data form one there • TB ( Manaye, MSC): 284 lab and case is lots of forms are entered for each data double entered. • Childhood vaccination and preparedness against seasonal and pandemic influenza: prospects for cellular immunity Double data Data Management and Biostatistics
entry done: 106 patients' CRFs data • Bio-Equivalence Place: Addis Ababa University Ciprofloxacin BE Study and We started Organizer: Emory University Bioequivalence study of oral co-trimoxazole Objective of the Training: The objective of prepared SOP for the Data Management the training is to develop the skills in R- including preparing data management statistical software for data management quality control and quality assurance SOP and data analysis. and check list; Designed CRF and Form of presentation: lecturing and online Designed the database with OpenClinica Taken by: Samuel Ayele, Hiwot Tilahun, • Leprosy Mapping Study (Dr.Saba Lambert): data entry done for a lot of leprosy cases in GCP refreshment Training for Bio-Equivalence
specificity and scope of the research such as large consortium driven externally funded projects, local MSc or PhD student research, and individual staff scientist research. In general, the lab team is being continually upgraded to cope with the increasing demand in services and standards. AHRI-GSK GCP Training
The major activities performed by the team in the • AHRI was chosen among other contenders by last year have been: 1) facilitating laboratory GSK to conduct GCP training for Clinical Trials practical attachments for 263 under-graduate and staff from Gondar and Jimma Universities; a post-graduate students from different Universities confirmation for the trust in AHRI as a centre throughout the country, 2) facilitating procurement of excellence for clinical trials. The training of the two large autoclaves and security doors for was in mid- July, 2014 for four full days. A the laboratory, 3) coordinating the the World TB good number of AHRI staff members were day celebration which involved inviting 86 students among the Trainers and Facilitators. from government and private schools and others from civil society to visit the research laboratory Upcoming Training: AHRI-AAU Emory Bioethics
and explain about the research works on TB. These activities are oriented to help motivate students in the area of biomedical science and create • AHRI staff including the Data Manager awareness to the civil society. The Laboratory together with other trainers will be providing Team was also involved in preparation of needed documents to fulfil the ISO 15189 requirements to grantees from 11 – 13 November, 2014 at the training centre. There will also be 27 SIDA accreditation. In addition to this, the lab team gave applicants who will be joining the course. technical assistance and support to different projects including MSc and PhD students. AHRI Laboratory Management Unit
participated in research evaluating the performance of microscopy for diagnosis of TB lymphadenitis by established in order to organize the infrastructure fine needle aspirates. and maintenance of the laboratory to create an optimal research environment. The research laboratory comprises six units, namely clinicaltrial, Project Managment, Finance and
Bacteriology, and Pathology Laboratories. One of the major contribution areas of AHRI for These laboratories are equipped with high tech national competence in health research and biomedical equipments such as Real Time and practice is institutional strengthening. In order to conventional PCR machines, FACSCanto and develop research capacity, the existence of skilled FASCan flow cytometers, Luminex machine, and well-functioning research support services machines, and clinical laboratory machines such as management and research Ethics is vital. a Clinical Chemistry and Hematologyanalyzers. Each of the six units have their own coordinator This year, a great milestone was achieved in and the whole process led by a laboratory manager. The lab engineer is primarily responsible procurement unit for AHRI which was previously for handling preventive and curative maintenance structured as part of the ALERT centre whose and calibration of the biomedical equipment. mission is primarily patient care. The unit is setting up a system under a newly employed coordinator Currently, various research activities are underway who is accountable to AHRI's Scientific Director. in these laboratories based on their technical As this is the first year that the unit has been functional there have been short term growing major objective has been accomplished which was pains as the unit transitioned from ALERT, but a to identify gaps in the previous system and establish a better functioning system for the future. project operations: effective use of funding Recent reviews have also identified on the accounting practices that AHRI should work on government, senior management and collaborators, such as updating the accounting system with the monitoring project progress, initiating researchers latest software. Currently, skilled human power has to respond to grant calls and facilitate submission. been employed, SOPs drafted, procurement This year, a new Research Training coordinator administration training has been given to all has been employed particularly to follow up and researchers and Finance and procurement team by monitor progress of Postgraduate Research the experts from public and procurement agency. Training Program at AHRI which is expanding and recruiting research trainee's from the universities in To create a conducive research environment and most parts of Ethiopia to strengthen National result, the Project management office is also competence to health care needs though informed providing support to researchers in following up AHRI/ALERT Ethics Review Committee
The AHRI/ALERT Ethics Review Committee Committee also received recognition from the (AAERC), as the name stands, reviews research Strategic Initiative for Developing Capacity in protocols and facilitates the conduct of research Ethical Review (SIDCER) in 2009 and since then, it that are planned to be conducted at AHRI or continues to strive for better performance in its elsewhere in collaboration with AHRI and ALERT. organization, review process, report delivery and The Committee has its own standard operating documentation and archiving. The Committee held procedures (SOP) that helps it to function optimally two internal audits since its recognition from with competence and consistency. In addition to the SIDCER; reviewed its internal practices, prepared existing SOP, the Committee also developed two and submitted manuscript for publication to one of new SOPs on reviewing protocols involving the local journals for educational purpose by other biorepository/biobank specimens and social and similar committees in the Country. Apart from the behavioral studies involving human subjects. With a regular review practices, the AAERC also provides technical and advisory support from the World short term trainings on research ethics, good Health Organization, Special Program for Research and Training in Tropical Diseases (WHO/TDR), the Members of the AAERC during one of the internal audit report meetings (taken in 2013) AHRI Alumini
Melat Tsegaye,
University of Gondar
PhD student at
Penn state
I joined AHRI during a University, USA
time when I did not have good know how about I joined AHRI in the the various aspects of year 2013 through the yearly graduate proposal development, student recruitment program that the institute undertakes knowledge of different advanced laboratory where accepted students get fully funded to techniques, scientific presentations and write- conduct their thesis research in the institute. ups. These are fundamental components one Once accepted, I was able to choose from should know to be a good researcher. I was prodigious researchers an advisor in my area of lucky to get an opportunity to conduct my interest that mentored me throughout my thesis research (MSc and part of my PhD work) at AHRI which enabled me to exploit the above opportunity to learn from scientists that I aspire mentioned components during my stay. Even to be like in the future. My thesis research was though I am now working at the University of titled "HIV-1 Gag specific polyfunctonal, Gondar, I still have working link with AHRI and proliferative and cytolytic CD8 T-cell response currently am doing several collaborative in elite controllers and long term non- progressors in Addis Ababa, Ethiopia. Aside publications beyond my thesis work. I gained from providing lab bench and the necessary the experience of working in a team from AHRI, reagents, AHRI provided me the logistic and too. Indeed, the impact of AHRI on my current administrative support that I needed to status and to build my future carrier has been complete my research. As a whole, AHRI was immense and indispensable. Apart from the not only a work place, but also a platform that research area, I gained knowledge and presented the crucial exposure I needed to experience of leadership, team spirit, and how grow as a phenomenal researcher. I am now a to overcome challenges. My MSc work was PhD candidate in Penn state University, "Genotyping of human papillomavirus in Pennsylvania, USA, and I credit my success to paraffin embedded cervical tissue samples from the work I did in AHRI that served as a stepping women in Ethiopia and the Sudan''. My PhD stone to where I am now. I am ever so grateful! work was "Impact of Helminth infections on the immunological and clinical features of active Tuberculosis: a double blind randomized trial." I am working with assistant professor rank in the Department of Immunology and Molecular Biology, University of Gondar. In addition, I am the head of the newly established research center "Tropical and Infectious Diseases Research Center" at the University of Gondar. Baye Gelaw,
Girmay Desalegn, PhD student at
PhD, University
Hannover Medical School in Hannover,
of Gondar
I did my master's thesis entitled "M. frequency of lipid specific Functional tubercle bacilli in human sputum" . HIV and Latent TB Co-Infections with fourspoligotyping and drug susceptibility assays were accomplished at AHRI and Ethiopia, Armauer Hansen Research Institute was fully sponsored by AHRI. At the same timeAHRI also secured my living expenses Postgraduate support program of AHRI in so during my stay in Addis Ababa which was many ways ranging from covering my thesis around two months. Moreover, my sample expenses to teaching me what science transportation to England was also with the practically is with hands-on lab works. In help of AHRI. Dr Abraham Aseffa was my addition, I have met numerous amazing and in country supervisor. inspiring people who taught me a lot in-and out- Currently, I am working at University of side the lab. I loved the attitude and spirit I saw Gondar teaching Medical microbiology in AHRI, which was a huge lesson to me. AHRI courses for medicine and other Health helped me participate in several summer Science students. I am also supervising 4 school, workshops and conferences which I to 5 MSc students each year and also I used them to expose myself and get to know have 4 research projects (2 as PI and 2 as co-investigator) together with laboratory backgrounds. This is why I am grateful to AHRI services for the hospital of College of for letting me explore my path and put me Medicine and Health Sciences, University of Gondar services for the hospital of College of Medicine and Health Sciences, University of Gondar. Publications
Abate E, Elias D, Getachew A, Alemu S, Diro E, Ethiopia: a cytopathlogic analysis. Ethiop Med J Britton S, Aseffa A, Stendahl O, Schön T. Effects 2014; 52(1):19-25.
of albendazole on the clinical outcome and 11. Bobosha K, Tjon Kon Fat EM, van den Eeden SJ, immunological responses in helminth co-infected Bekele Y, van der Ploeg-van Schip JJ, de Dood CJ, tuberculosis patients: a double blind randomised Dijkman K, Franken KL, Wilson L, Aseffa A et al: clinical trial. Int J Parasitol 2014. Field-evaluation of a new lateral flow assay for Abdissa A, Yilma D, Fonager J, Audelin AM, detection of cellular and humoral immunity against Christensen LH, Olsen MF, Tesfaye M, Kaestel P, Mycobacterium leprae. PLoS Negl Trop Dis 2014; Girma T, Aseffa A et al. Drug resistance in HIV 8(5):e2845.
patients with virological failure or slow virological 12. Bobosha K, Wilson L, van Meijgaarden KE, response to antiretroviral therapy in Ethiopia. BMC Bekele Y, Zewdie M, van der Ploeg-van Schip JJ, Infect Dis 2014; 14:181.
Abebe M, Hussein J, Khadge S, Neupane KD et al. Abseno M, Aseffa A, Shimelis E, Wassie L, Abebe T-cell regulation in lepromatous leprosy. PLoS M, Mitikie G, Yamuah L, Ali A: Tuberculosis Negl Trop Dis 2014; 8(4):e2773.
among Addis Ababa city bus drivers and cash 13. Deribe K, Brooker SJ, Pullan RL, Sime H, collectors. Ethiop Med J 2014; Suppl 1:31-35. Gebretsadik A, Assefa A, Kebede A, Hailu A, Alemayehu M, Gelaw B, Abate E, Wassie L, Rebollo MP, Shafi O, Bockarie MJ, Aseffa A, Belyhun Y, Bekele S, Kempker RR, Blumberg Reithinger R, Cano J, Enquselassie F, Newport MJ, HM, Aseffa A. Active tuberculosis case finding Davey G. Epidemiology and Individual, Household and detection of drug resistance among HIV- and Geographical Risk Factors of Podoconiosis in infected patients: A cross-sectional study in a TB Ethiopia: Results from the First Nationwide endemic area, Gondar, Northwest Ethiopia. Intl J Mapping. Am J Trop Med Hyg 2015;92(1):148-58
Mycobacteriol 2014; 3.
14. Ferraro CF, Trotter CL, Nascimento MC, Jusot JF, Aseffa A, Mihret A, Habte A, Gadisa E, Beyene D: Omotara BA, Hodgson A, Ali O, Alavo S, Sow S, Seizing the opportunity for better organization of Daugla DM et al. Household crowding, social health research. Ethiop Med J 2014, Suppl 1:2 p mixing patterns and respiratory symptoms in seven countries of the african meningitis belt. PLoS One
2014; 9(7):e101129.
Aseffa A, Rusen ID. Strengthening operational research in Ethiopia: beyond training for a 15. Gebreegziabiher D, Desta K, Desalegn G, Howe R, sustainable and successful country OR programme. Abebe M. The effect of maternal helminth infection Public Health Action 2014; 4 (Sup 3): S1-S1(1).
on maternal and neonatal immune function and immunity to tuberculosis. PLoS One 2014; Ashenafi S, Aderaye G, Bekele A, Zewdie M, Aseffa G, Hoang AT, Carow B, Habtamu M, Wijkander M, Rottenberg M et al. Progression of 16. Gebreegziabiher D, Desta K, Howe R, Abebe M. clinical tuberculosis is associated with a Th2 Helminth infection increases the probability of immune response signature in combination with indeterminate QuantiFERON gold in tube results in elevated levels of SOCS3. Clin Immunol 2014; pregnant women. BioMed research international 2014; 2014.
Bekele S, Bekele Y, Mulatu F, Lemma T, Tilahun 17. Geluk A, van Meijgaarden KE, Wilson L, Bobosha H, Gadisa E, Negussie S, Yamuah L K, van der Ploeg-van Schip JJ, van den Eeden SJ, Quinten E, Dijkman K, Franken KL, Haisma EM, Leekassa R, Bizuneh E. Recent trends of Haks MC, van Hees CL, Ottenhoff TH. cutaneous leishmaniasis in Alert Hospital, Addis Ababa. Ethiop Med J 2014; Suppl 1:37-41. expression profiles in type 1 leprosy reactions. J
2014; 34(2):245-55
Berhe G, Enquselassie F, Aseffa A. Assessment of Risk factors for development of active pulmonary 18. Ghansah A, Amenga-Etego L, Amambua-Ngwa A, tuberculosis in Northern part of Ethiopia: a Andagalu B, Apinjoh T, Bouyou-Akotet M, matched case control study. Ethiop Med J 2014; Cornelius V, Golassa L, Andrianaranjaka VH, Ishengoma D, et al. Monitoring parasite diversity for malaria elimination in sub-Saharan Africa. 10. Bezabih M, Abdissa A, Gadisa E, Aseffa A. Science 2014; 345(6202):1297-1298.
Patterns of enlarged cervical lymphnodes among HIV positive and negative patients in southwestern 19. Golassa L, Enweji N, Erko B, Aseffa A, Swedberg G: High prevalence of pfcrt-CVIET haplotype in isolates from asymptomatic and symptomatic Aseffa A, Parida SK: T cell response to alpha patients in south-central Oromia, Ethiopia. Malar J crystallin and Mycobacterium tuberculosis specific 2014; 13:120.
antigens using ex-vivo elispot assay for detecting latent tuberculosis infection in Addis Ababa, 20. Herrador Z, Sordo L, Gadisa E, Buño A, Gómez- Ethiopia. Ethiop Med J 2014, Suppl 1:15-22. Rioja R, Iturzaeta JM, de ArmasLF, Benito A, Aseffa A, Moreno J, Cañavate C, Custodio E. 29. Mariam SH, Zegeye N, Tariku T, Andargie E, Micronutrient deficiencies and related factors in Endalafer N, Aseffa A: Potential of cell-free school-aged children in Ethiopia: a cross-sectional supernatants from cultures of selected lactic acid study in libokemkem and fogera districts, amhara bacteria and yeast obtained from local fermented regional state. PLoS One 2014; 9(12).
foods as inhibitors of Listeria monocytogenes, Salmonella spp. and Staphylococcus aureus. BMC 21. Herrador Z, Sordo L, Gadisa E, Moreno J, Nieto J, Res Notes 2014; 7:606.
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Abebe Habetie Dessie Alemayehu Kifle Tesema Almaze Kiros Mebiratu Asayech Dagne Wubete Banchayehu Gualu Geremew Belayinesh Beyene Asfaw Birhanie Tedela W/Mariam Hiwot Tilahun Debalkie Kidist Bobosha Aboma Martha Zewdie Gebeyehu Meheret Teshome Teferi Menberwork Chanyalew Negatu Miteku Werede Engeda Saba G/Tsadik Woya Semene Begashaw Masresha Tarekegne Feleke Yebrgol Wogayehu Alemu G/Hiwot Wondu Wagaye Yanda Wude Miheret W/Medhin A Tribute to Agerie Tadele (12th AHRI Tore Godal Prize award winner) Agerie was one of the young outstanding researchers at AHRI admired for her dedication and commitment. We are very saddened by her untimely death. We remember her always as an amazing person who had been cheerful, smiling and hardworking With our deepest sympathy, Rest in peace Agerie!

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