Browsing by Author "Hailu, Asrat(Professor)"

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    Identification of Anti-Leishmanial Leads from Open Access Pathogen Box
    (Addis Ababa University, 2019-01) Tadele, Markos; Mequanente, Solomon(PhD); Makonnen, Eyasu(Professor); Hailu, Asrat(Professor)
    Leishmaniasis is a vector-borne disease caused by an obligate intracellular protozoan of the genus Leishmania. The ranges of drugs available to treat this disease are limited; therefore, there is a substantial need to develop new medicines or drug combinations. Aiming to find potential anti-leishmanial leads, we screened MMV Pathogen Box for two strains of leishmania parasites. In this optimised, medium throughput primary screening assay, all 400 compounds were screened against promastigotes and amastigotes stages of L. donovani and L. aethiopica. The screen yielded a total of 16 hits with IC50 ranges from 0.01 to 0.555 μM on anti-promastigote assay and 0.05 to 0.7 μM on intracellular amastigote assay, respectively. Two compounds, known by MMV690102 and MMV688262 were identified as lead compounds for L. aethiopica and L. donovani. Cytotoxic effect of selected hits and synergistic effect of lead compounds with common reference drugs was also investigated. All selected compounds demonstrated good safety for the mammalian cell they were tested. The anti-TB drug (delamanid) showed synergistic effect with Amphoterecin B. This indicates the prospect of this compound for combination therapy. MMV690102 demonstrated inhibitory activity on both tested strains indicating its broad spectrum in activity. Future works should investigate antiamastigotes activity of those ‘hits’, which are not covered in the present study, and Identified lead compounds should progressed to other pre-clinical studies and their mechanism of action should be investigated using target based experiments.
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    Immunogenicity of Leishmania Derived Antigens in Peripheral Blood Mononuclear Cells Using Blood Obtained from Previously Treated Visceral Leishmaniasis Patients of Southwest Ethiopia
    (Addis Ababa University, 2015-06) Demeke, Gebreselassie; Hailu, Asrat(Professor)
    Background:-Visceral leishmaniasis is a public health problem and it is fatal if untreated. Disease burden is associated with poverty, lack of effective, affordable, and minimally toxic treatments. An effective vaccine is needed to combat this disease. Method: - Peripheral blood mononuclear cell-based assays were set-up in blood samples obtained from 5 healthy controls and 18 drug-cured VL patients (DC-VL), who are putatively immune to re-infection. For PBMCs stimulation nine Leishmania derived antigens were selected, and together with whole promastigote lysate antigen and Phytohaemagglutinin (PHA), and assessment of immunogenicity was carried out by cytokine assays using ELISA kit. The assay aimed at measuring IFN-gamma, TNF-alpha, IL-10 and IL-5 in culture supernatants of PBMCs stimulated in vitro. The association of cytokine production with immunogenicity difference of antigens was determined by using non-parametric tests (Mann Whitney & Tukey’s Multiple Comparison tests) found in Graph Pad Prism version 6. Result: - Drug-cured visceral leishmaniasis (VL) patients develop protection mediated by Th1-type cellular responses against new infections. IFN-gamma, TNF-alpha and IL-10 production were higher in drug-cured groups, but neither drug-cured nor healthy controls produced IL-5. The data suggest the mounting of Th1 type responses upon cure from visceral leishmaniasis, while small amounts of IL-10 were also measurable. NS, S, PNS and NSL were more immunogenic than other antigens as determined by levels of IFN-gamma, TNF-alpha and IL-10. Conclusion:-This study indicates that T cell recall ability of humans cured from VL by chemotherapy was conspicuous and related to Th1 type immune response. Further, the data confirm that high levels of IFN-gamma and TNF-alpha in the presence of low levels of interleukin-10 (IL-10) could be proxy indicators of protective immunity in drug-cured visceral leishmaniasis patients. Among tested antigens NS, NSL, PNS and S were more immunogenic and elicited high levels of IFN-gamma and TNF-alpha in PBMCs of drug-cured patients, with supernatant levels ranging from16 to1826 mg/ml. Key words: Antigen immunogenicity, visceral leishmaniasis
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    Preliminary Investigation on Immune Response of Schistosoma Mansoni in Grivet Monkeys (Cercopithecus Aethiops Aethiops) Infected with Different Cercarial Doses
    (Addis Ababa University, 2006-07) Demelash, Tariku; Hailu, Asrat(Professor)
    In order to evaluate grivet monkey (Cercopithecus aethiops aethiops) as an animal model for the immune response of mansonian schistosomiasis, groups of three or four grivet monkeys were exposed individually to 100, 200, and 300 cercariae per monkey. Infection and clinical manifestations were observed; EPG of stool was determined and different cytokines (IL-12, IFN- , TNF- , IL-4 and IL-10) were measured. Infected monkeys began to release eggs 7 weeks post infection. Most of them became ill 7 to 9 weeks after initial exposure and exhibit most of the clinical manifestations typical of human acute schistosomiasis. The fecal egg count confirmed there is significant (P<0.05) variation between groups in terms of numbers of eggs released in stools, where the group that receives the lowest cercariae dose exhibiting the highest egg output. There was a significant difference in the level of cytokine production between those infected and the controls. Th1 cytokine (IL-12, INF-gamma, and TNF-alpha) levels reached their highest before their Th2 counter part (IL-4). Cytokine levels, however, were not found to be dose-dependent as anticipated. Comparison of this study with studies on related primates suggests that grivet monkey closely resemble the baboons in their immune response to Schistosoma mansoni infections. Thus, this work may underline the potential of the grivet monkey to provide a cheaper, more readily available primate model for the study of the immune response and the acute stage of infection by S. mansoni
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    The Prevalence of Geohelminth and S. Mansoni Infections and Associated Risk Factors Among School Children in Umolantie, South Ethiopia
    (Addis Ababa University, 2011-05) Alemu, Megbaru; Fikrie, Nigus; Hailu, Asrat(Professor)
    Introduction: The prevalence and distribution of intestinal helminths varies from place to place in Ethiopia. Intestinal parasitic infections have detrimental effects on the survival, appetite, growth and physical fitness, school attendance and cognitive performance of school age children. Higher parasitic disease rates occur in children with infection frequently found in those under 14 years in many risk areas due to poor hygiene and play habits. Objective: To determine prevalence and associated factors of intestinal helminthic infections among Umolantie primary school children, South Ethiopia. Methodology: A cross-sectional study, involving 405 schoolchildren, was conducted between Nov, 2010 and Jan, 2011. Systematic random sampling technique was applied. Interviews and observation were used to identify the risk factors. Stool specimens were examined using the Kato-Katz technique. Data was entered and analyzed using SPSS 16.0 and odds ratio, confidence intervals and p-value were calculated. Results: six species of intestinal helminths were identified with an overall prevalence of 26.9% (109 of 405 children). The predominant parasites involved were hookworm spp. 59(14.6%) and S. mansoni 51(12.6%). Prevalence of S. mansoni infection was significantly higher in males (p=0.006), whereas hookworm infection was significantly higher in females (P=0.015). Bathing in the stream was strongly associated with higher prevalence of S. mansoni infection (p=0.03). Other helminths found were E. vermicularis 1% (4 cases), whipworm 1.5% (6 cases) and tapeworm 1.5% (6 cases) and A. lumbricoide 0.5% (2 cases). Conclusion and recommendation: A high percentage of primary school children from Umolantie have intestinal helminth infections and majority of them have hookworm and S. mansoni. Hence the community should be provided with safe water and should uphold awareness about the main routes of transmission of intestinal helminthes. School children should avoid water contact habits in the nearby stream and regular shoe wearing habits should also be developed among them. Key words: geohelminths, S. mansoni, school children, Umolantie, South Ethiopia
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    The Prevalence of Malaria and Community Knowledge, Attitude and Practice about the Transmission and Control Measures Among Households in Pawe Woreda, North West Ethiopia
    (Addis Ababa University, 2011-05) Bedemo, Habtamu; Hailu, Asrat(Professor); Fikrie, Nigus
    Background - Epidemiological information regarding the prevalence of various parasitic infections in different localities is a key to develop appropriate control strategies. A High Knowledge score about the cause, transmission and habit of practicing the available effective preventive and control measures by the individual households and the community at large could contribute much to the overall reduction of the malaria burden. Objectives - To determine the prevalence of malaria and asses the community knowledge, attitude and practice about the transmission, prevention and control measures among households at Pawe Woreda, North West Ethiopia. Methods and Materials - A community based, cross sectional study was carried out from November to December, 2010. A multi-stage random sampling technique was carried out to select representative households. A pre tested structured questionnaire (n=406) and blood film examination format (n=403) were used for data collection. Data was entered and analyzed using SPSS 16.0. Proportions, Odds ratio and 95% CI were computed. Results - The overall malaria prevalence was 14.7%. Respondents that mentioned at least three symptoms of malaria constitute 71.5%. Fifty six percent of the respondents associated malaria with hunger/skipping meals, as a cause and most (67%), affirmed that mosquitoes transimt the disease. Significant proportions (79.8%) were aware that mosquitoes bite during night. Use of bed net and draining of stagnant water were identified as major malaria preventive measures by 89.7% and 34% of respondents, respectively. About 69.2% reported that they were using bed nets correctely. Over 50% of the respondents stated that they would not seek for malaria treatment in 24 hours. Participants who had many years education ( > 5th grade) and those who received health education reported high malaria Knowledge score, correct use of bed nets and early treatment seeking habits [OR (95%CI) =4.9(1.4-8), 1.8(1.4-2.5), 2.2(1.7-4.1), respectively. Living in areas which would take 60 minutes and longer distances to health facility was found to be associated with delay in treatment (OR=1.3, 95%CI= (1.1-2.0). Conclusions and recommendation - The Prevalence of malaria reported in this study was higher than reports in many areas of the country. Though malaria knowledge score viii among the study participants were observed to be more than 50%, the practice of effective preventive and control measures were relatively poor. Hence, a comprehensive health education and promotion of community education should be given with a special emphasis given to assure that individual households use ITNs correctly, adapt integrated vector control approach, avoid misconception about cause of malaria and seek treatment early. Key words - Prevalence, knowledge, attitude, practice, community, early treatment seeking behavior, high knowledge score, correct use of ITNs.