DSpace Community: Faculty of Science

Innate Immunity to Tuberculosis in advanced HIV/AIDS patients

Mon, 22 Apr 2013 07:10:07 GMT

Title: Innate Immunity to Tuberculosis in advanced HIV/AIDS patients

Authors: Tewodros, Tariku

Abstract: Several factors influence resistance or susceptibility to tuberculosis (TB) in an immunocompromised host. Animal studies have shown the contributions innate immunity on host resistance to TB disease in the absence of intact adaptive immunity (Feng et al., 2006). We extended these observations to humans to assess the innate mechanisms that prevent the development of active TB in advanced AIDS patients with compromised CD4+ T cell functions. In a cross-sectional study, we determined macrophage mediated killing of Mycobacterium tuberculosis (M. tuberculosis ) and measured the production of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10). We also assessed intracellular expression of IFN-γ in NK, γ/δ (CD3+ γ/δ+) and adaptive (CD3+ γ/δ -) cells in response to purified protein derivative (PPD) and live M. tuberculosis . We found better innate functions in macrophage killing and IFN-γ production in AIDS patients with latent TB infection compared to AIDS patients who progress to TB disease, but the differences did not reach statistical significance. The study suggests that variation in susceptibility to TB in AIDS patients could be due to innate immunity but our observation warrants confirmation in larger prospective study to consolidate this hypothesis. A better understanding of these factors might help in making preventive therapies to HIV patients that are most likely to develop TB.

Description: A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science (Applied Microbiology Stream)

Analysis of Humoral Immune Response to a Panel of Plasmodium falciparum Blood- Stage Vaccine Candidate Antigens in Naturally Primed Populations in Seasonal Malaria Settings in Ethiopia

Mon, 22 Apr 2013 07:04:36 GMT

Title: Analysis of Humoral Immune Response to a Panel of Plasmodium falciparum Blood- Stage Vaccine Candidate Antigens in Naturally Primed Populations in Seasonal Malaria Settings in Ethiopia

Authors: Hassen, Mamo

Abstract: In Ethiopia, the general population is quite vulnerable to unpredictable cyclic epidemics of Plasmodium falciparum malaria. However, there is very little information on the anti-malaria immune profile of the population residing in the endemic regions of the country. This study was designed to investigate the nature of humoral immune response to malaria in two population groups in two endemic localities, Shewa Robit in the north and Boditi in south. In a cross-sectional study, the study participants were diagnosed for malaria infection microscopically and by the rapid diagnostic test (RDT). The sera were tested by using enzyme-linked immunosorbent assay (ELISA) for total immunoglobulin (Ig) G against P. falciparum blood-stage vaccine candidate antigens: apical membrane antigen 1 (AMA1), glutamate-rich protein (GLURP) R2 region, and merozoite surface protein 2 (MSP2) allelic variants (3D7 and FC27) in Shewa Robit. Total IgG against GLURP-R0, MSP3 and GMZ2 and IgG subclasses against GLURP-R0 and MSP3 were assayed in both Shewa Robit and Boditi sera. Whereas 23(8.6%) blood-smear-positive cases for P. falciparum were detected in Boditi, all Shewa Robit study participants had no detectable P. falciparum infection. At both localities total IgG prevalence and levels to GMZ2 were significantly higher than the response to the component domains iv (GLURP-R0 and MSP3) indicating the induction of strong GMZ2-specific natural antibodies. There was significant difference between the median antibody level to GMZ2, GLURP-R0 and MSP3 compared to the responses to other antigens tested in Shewa Robit, indicating that GMZ2 could be a more relevant blood-stage malaria vaccine candidate antigen. Higher total IgG and subclass prevalence and levels were detected in Shewa Robit than Boditi, suggesting difference in the intensity of malaria transmission in the two localities and/or genetic differences between the two population groups in their response to blood-stage P. falciparum antigens. In both study sites, IgG subclass antibody levels to GLURP-R0 were significantly higher than that to MSP3 for all corresponding subclasses in most individuals, indicating the higher relative immunogenicity and protective potential of GLURP-R0 compared to MSP3. Against both GLURP-R0 and MSP3, the ratio of cytophilic to noncytophilic antibodies was >1 in the majority of the study participants, in both study sites, indicating the induction of protective antibodies against the two antigens. Analysis of age-related pattern in antibody levels against the antigens tested showed a positive association with increasing age for most antigens suggesting the role of intrinsic agerelated factors in immune maturation. The age factor appears plausible as there was no evidence for increase in antibody response with increasing frequency of reported past clinical malaria. Overall, the study has shown that Ethiopian population groups residing in unstable and seasonal malaria epidemiological settings have a high prevalence and levels of long-lived antibodies that readily recognize P. falciparum blood-stage vaccine candidate antigens, particularly GMZ2 and its component fractions (GLURP-R0 and MSP3). Furthermore, detection of high level antibody responses in non-febrile smear-negative individuals without history of reported past malaria episodes may possibly be an indication of a low-grade, asymptomatic (submicroscopic) infections in the induction and maintenance of high level protective v immunity. Therefore, to determine the implication of submicroscopic infections in the induction and boosting of malaria immunity versus the existence of long-lived malaria-specific antibodies in the absence of boosting from submicroscopic infection, PCR confirmation of the microscopy-negative samples would be necessary.

Description: A Thesis Submitted to the Department of Microbial, Cellular and Molecular Biology Presented in Fulfillments of the requirements for the Degree of Doctor of Philosophy (Biomedical Science)

Antibacterial Activity of Moringa stenopetala against Some Human Pathogenic Bacterial Strains

Mon, 22 Apr 2013 06:46:30 GMT

Title: Antibacterial Activity of Moringa stenopetala against Some Human Pathogenic Bacterial Strains

Authors: Basha, Chekesa

Abstract: An emerging of antibiotic resistance brings most serious public health problems. It is therefore, important to look for more effective, safer and less toxic alternate options of treatment. The aim of the present study was to investigate antibacterial activity of Moringa stenopetala against some human pathogenic bacteria using disk diffusion method and agar dilution for minimum inhibitory concentration. The result revealed that, most of the plant extracts had antibacterial activity. Staphylococcus aureus was found to be the most susceptible bacteria to crude 80% methanol extract of seeds and ethyl acetate extract of root barks with inhibition zones of 18.66±0.88mm and 16.00±1.15mm and minimum inhibitory concentration of 1.25mg/ml and 2.5mg/ml respectively, whereas Pseudomonas aeruginosa was the most resistant bacteria to all of crude extracts. Similarly, Staphylococcus aureus was the most susceptible bacterial strain to chloroform fraction with inhibition diameter of 28.00±0.57mm and minimum inhibitory concentration of 0.31mg/ml, while Pseudomonas aeruginosa was the most resistant strain with inhibition zone of 9.66±0.33mm and minimum inhibitory concentration of10mg/ml respectively. In conclusion, this study is not only proves antibacterial activity of Moringa stenopetala, also provides a scientific basis for their traditional use. Pure chemical compounds and antimicrobial activity against many fungi and bacteria should be studied to use them as sources and templates for synthesis of drugs to control infectious diseases.

Description: A Thesis Submitted to the School of Graduate Studies of Addis Ababa University and Presented in Partial Fulfillment of the Requirements for the Degree of Masters of Science in Applied Microbiology Stream

ASSESSMENT OF THERAPEUTIC EFFICACY OF COARTEM® IN PATIENTS WITH UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA IN HALABA SPECIAL WOREDA, SOUTHERN ETHIOPIA

Mon, 22 Apr 2013 06:36:07 GMT

Title: ASSESSMENT OF THERAPEUTIC EFFICACY OF COARTEM® IN PATIENTS WITH UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA IN HALABA SPECIAL WOREDA, SOUTHERN ETHIOPIA

Authors: MAHLET, LEMMA

Abstract: Emergence of malaria parasite drug resistance is a serious problem in malaria control. Artemether-lumefantrine (Coartem®) is used as a first line treatment for uncomplicated falciparum malaria since 2004 in Ethiopia. The objective of the study was to assess the efficacy of Coartem® against falciparum malaria in Halaba Special Woreda, Southern Ethiopia. 5922 individuals that were clinically suspected of malaria were screened for infection. Giemsa stained thin smears were used for identification of Plasmodium species, and thick smears for detection and quantification of the parasites. Among the screened, 1826 (30.8%) were malaria positive, of which 273 (14.9%) were due to Plasmodium flaciparum and 1553 (85.1%), due to Plasmodium vivax. Among Plasmodium flaciparum positive patients, 89 (32.6%) fulfilled the inclusion criteria and were enrolled in the study. Haemoglobin concentration of the study participants was measured on days 0, 14 and 28 using portable spectrophotometer. Study outcomes were classified as early treatment failure (ETF), late clinical failure (LCF), late parasitological failure (LPF) and adequate clinical and parasitological response (ACPR). Out of the 89 study participants, 6 (6.7%) were lost to follow up and 3 (3.4%) withdrew from the study. Following drug administration, parasitemia cleared from all the study participants on day 3, and almost all fever cleared on day 2. Gametocytes were detected in 9% of the study participants on the day of inclusion into the study, and none could be detected after day 7. During follow up, one patient became positive for Plasmodium flaciparum, amounting to a 1.3% LCF, as a result of which the cure rate of Coartem® in the study area was 98.7% (95% CI=93.2-100%). However, as a confirmation of emergence of Coartem® resistance in the study area, it will be necessary to do a PCR correction to determine whether the 1.3% LCF was a new infection or a recrudescence. The mean haemoglobin level of the study participants was 10.8g/dl (Range: 9.2g/dl-13.7g/dl) on day 0, of which 57.3% were anemic. On day 28 of follow up, mean haemoglobin level significantly increased (P=0.002), compared to day 0, and the proportion of anemic individuals declined. The overall findings of the study have shown high efficacy and safety of Coartem® for treatment of uncomplicated falciparum malaria, in the study area. Also, the high prevalence of P. falciparum and P. vivax malaria, detected in the study area, indicated the ineffectiveness of the control measures in practice. Therefore, the malaria situation in Halaba Special Woreda requires initiation of more effective integrated control measures and periodic monitoring of anti-malarial drug efficacy.

Description: A Thesis Submitted to the School of Graduate Studies of the Addis Ababa University in Partial Fulfilment of the Requirements for the Degree of Master of Science in Biology (Biomedical Science)