Design, synthesis and biological evaluation of novel epigenetic modulators for parasitic diseases

Current therapies for human parasite infections rely on a few drugs, most of which have severe side effects, and their usefulness is being seriously threatened by the drug resistance problem. Globally, this is pushing anti-parasitic drug discovery research towards new agents endowed with novel mechanisms of action. Epigenetic processes and the histone modifying enzymes perform vital functions in parasite growth and survival and are validated therapeutic targets. A wealth of current literature indicates that by the use of the so called “drug repurposing” approach, small molecule epigenetic modulators, which were originally developed to treat other human disease conditions, are being investigated for treatment of parasitic diseases, including P. falciparum and S. mansoni infections. The current project focuses on the development and synthesis of novel epigenetic modulators as potential antimalarial and antischistosomal agents. The first part of the project deals with the target-based drugs approach using a small library of HDAC inhibitors to identify potential antimalarial agents. Antiplasmodial activity revealed that MC1742, a uracil-based hydroxamide HDAC inhibitor, as a potent compound with an IC50 value of 4 nM and 6 nM against Pf3D7 sensitive and W2 multidrug resistant strains, respectively. Another project deals with development and synthesis of smSirt2 inhibitors, where several compounds showed modest activity against S. mansoni and good selectivity over hSirt2 that could be potentially used as hits/leads for further medicinal chemistry optimization. Finally, as far as the LSD1 inhibitors as potential antischistosomal agents is considered, preliminary data indicated that most of the tested compounds were relatively toxic to the juvenile stage of schistosomula and to a lesser extent to adult worms. Among these tested compounds, MC3935 was found to be extremely toxic to both schistosomula and adults. Taking into account the preliminary effects of these compounds, it has been demonstrated, as expected, that histone demethylase inhibitors are essential and attractive targets for development of new antimalarial and antischistosomal agents

A study on abundance, group size and composition of Soemmering's Gazelle (Gazella soemmerringii) in Awash National Park and Alledeghi Wildlife Reserve, Ethiopia

Population status, group composition and social organization of the Soemmerring's gazelle (Gazella soemmeringii) were studied at Awash National Park (ANP) and Alledeghi Wildlife Reserve (AWR) in 2000. Total count method was used to assess the population size of the gazelle. Thirteen routes, each route being two kilometres away from the other, were designated at AWR for the vehicle survey. Similarly, 10 routes, each being one kilometre away from the other, were designated at ANP. The results revealed a mean population of 457.8 individuals in the selected study site in Alledeghi Wildlife Reserve, and 41.45 in Ilala Sala. Grouping pattern showed that cohesion was stronger. The large females group containing juveniles and of adult males were the two main social units. Mean group size in ANP was 4.4 whereas that of AWR was 16.8 individuals (p>0.001). A paired-sample t-test comparison of the total frequency of categories of the group sizes for the two areas showed a significant difference (p=0.026). Local variation in group size did exist in AWR (p=0.021). But this variable showed no significant difference (p= 0.414) in ANP. Herds of 6–10 were most common at Ilala Sala and 20–50 at AWR. However, herd size ranges from 3–250 individuals at AWR. Comparing seasonal variations in group sizes showed no significant difference. It is presumed that alteration of the original habitats might have an effect on the group pattern and social organization of study population as observed from one of the study site. Keywords: abundance, Alledeghi Wildlife Reserve, Awash National Park, group size, Soemmerring's gazelleSINET: Ethiopian Journal of Science Vol. 28(2) 2005: 161-17

Classification of small ruminant production sub-systems in Ethiopia: Implications for designing development interventions

Part I of this working paper classifies small ruminant sub-systems in the mixed crop livestock system in Ethiopia. In Part II, important determinants of small ruminant productivity and producers’ input use and marketing strategies were analysed across the six small ruminant sub-systems identified in Part I. Classification of livestock production systems forms a useful framework for the spatial targeting of development interventions. Household and community level data collected from 497 communities and 2621 households were used to classify small ruminant sub-systems using principal components and cluster analyses. Exploratory analysis indicated variation and a clear structuring in livestock species and small ruminant flock composition and flock size in the mixed crop-livestock system. The variations were related to agro-ecologies and cropping patterns. Cluster analysis identified six clusters which were designated as sub-systems in the mixed crop-livestock system. The sub-systems were named following the dominant small ruminant species (sheep versus goat) and the degree of intensity/extensiveness of small ruminant production. The sub-systems were spatially characterized and described in terms of producers input use and marketing practices. Small ruminant production in Ethiopia could be classified into two systems (mixed crop-livestock and agro/pastoral) with six sub-systems within the mixed crop-livestock system or into seven systems (the six sub-systems and pastoral/agro-pastoral system)

Therapeutic Efficacy of Artemether-Lumefantrine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Northern Ethiopia

Introduction. Multidrug resistance of Plasmodium falciparum is spreading throughout Africa. This has posed major challenges to malaria control in sub-Saharan Africa. Objective. The aim of the study was to evaluate the efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in North Ethiopia. Methods. This prospective study was undertaken during August–November 2009 on 71 malaria patients that fulfilled the inclusion criteria set by the WHO. Patients were followed up for 28 days. Thick and thin blood films were prepared by Giemsa stain for microscopy to determine parasite density. A standard six-dose regimen of artemether-lumefantrine was administered over three days and was followed up with clinical and parasitological evaluations over 28 days. Results. The cure rate (ACPR) was found to be high (97.2%) in this study. The parasite and fever clearance time was also rapid. Artemether-lumefantrine for the treatment of acute uncomplicated Plasmodium falciparum malaria in the study area showed 97.2% cure rate and only 2.8% failure rate. Conclusion. The result showed that the drug could continue as first line for the treatment of uncomplicated Plasmodium falciparum malaria in the study area. The efficacy of artemether-lumefantrine needs to be carefully monitored periodically in sentinel sites representing different areas of the country

Analysis of village poultry value chain in Ethiopia: Implications for action research and development

This study aimed at developing a baseline understanding of producers, use of inputs, production performance, marketing, institutional and infrastructural environment and support services in order to identify potential areas of improvement for action research and poultry value chain system development in Ethiopia

Sheep and goat production and marketing systems in Ethiopia: characteristics and strategies for improvement

Ethiopia is home for a large and diverse livestock resources and favourable production environments. The vast majority of the rural population’s livelihood is partly based on livestock production. However, livestock production and productivity and producers’ benefits from livestock production are far below expectations. Understanding the livestock production and marketing characteristics and producers’ needs and perceptions, identifying constraints and opportunities, and designing workable production strategies are required in order to improve livestock productivity and market success of producers. Based on a series of IPMS studies, this paper synthesises and analyses the characteristics, constraints and opportunities of sheep and goat production and marketing in Ethiopia. The paper also puts forward strategic interventions for improving sheep and goat productivity and producers market success. Livestock production systems in Ethiopia have evolved largely as a result of the influence of the natural production environments and socio-economic circumstances of farmers/ pastoralists, rather than market forces. Livestock production is of subsistence nature. Like all other livestock species, sheep and goat in Ethiopia are kept under traditional extensive systems with no or minimal inputs and improved technologies, which results in characteristically low productivity. They are virtually kept as scavengers, particularly in the mixed crop–livestock systems. Sheep and goat are largely produced in mixed crop–livestock, specialized pastoral and agropastoral systems. Market-oriented or commercial production is almost non-existent. Small flock sizes predominate in the highland mixed crop–livestock systems because of land and capital limitations. Relatively larger flocks are maintained in the lowland (agro) pastoral systems. The major feed resources for sheep and goats include grazing on communal natural pasture, crop stubble, fallow grazing, road side grazing, crop residues, browses, and non-conventional feeds (household food leftovers, weeds, crop tillers and fillers). Production of improved forages, improvement of low quality feed sources such as crop residues and supplementary feeding (except fattening) is almost non-existent

Experience on mass hormonal oestrus synchronization and insemination of cattle to improve supply of dairy genetics under smallholder conditions in Ethiopia

<p><b>A.</b> Photograph in right oblique view. <b>B.</b> Photograph in rostral view. <b>C.</b> Interpretive line drawing in rostral view, with major reconstructed areas indicated in gray and matrix indicated in yellow. <b>Abbreviations: </b><b>aob</b>, antorbital buttress; <b>m</b>, matrix and metal supports; <b>nh</b>, nasal horncore. Scale bar equals 10 cm, but note that parallax prevents accurate measurement of parts of the skull caudal to the external naris.</p

AICCRA Scaling Vision: Ethiopia - Scaling and Scalability: Concepts, Frameworks, and Impact Pathways

Effective scaling up is a key measure of success for these innovations. Too often, however, the decision to scale up is made with incomplete information. Given the high costs involved, decision-makers (governments, development partners, NGOs, and the private sector) must carefully decide which innovations are ready for investment. A good understanding of the scaling-up process and a conceptual framework that informs the scaling vision, analysis of the scaling readiness of innovations, and impact pathways to achieve that vision are critical for informed decision-making. AICCRA Ethiopia is promoting the broader adoption of Climate information systems (CIS) and climate-smart agriculture (CSA) technologies through a series of pilot projects across a minimum of five major work streams