eRapport

Study on the role of antioxidants micronutrients on resolution of schistosomal peri-portal fibrosis of the liver.

Prosjekt
Prosjektnummer
2010087
Ansvarlig person
Svein Gunnar Gundersen
Institusjon
Oslo universitetssykehus HF
Prosjektkategori
Postdoktorstipend
Helsekategori
Infection
Forskningsaktivitet
6. Treatment Evaluation
Rapporter
2015 - sluttrapport
In this translational study, we collect samples and analyse antioxidant levels of Ethiopian foods and patient samples in Aklilu Lemma Institute of Pathobiology, Addis Ababa University, and in the Nutrition Institute, University of Oslo. In parrticular, wee explore the effects of antioxidant rich foods on schistosomal liver fibrosis, a major debilitating consequence of this neglected tropical diseases. During the years of the project we have published a number of papers on the antioxidant effect of leaves of the Moringa stenopetala tree and other food ingredients, traditional food habits and feasibility of adapting antioxidant rich foods in new geographical areas. We have also followed a cohort of 150 students in Northern- and Southern Ethiopia for 9 years (started before the project period) on their antioxidant blood Levels and liver fibrosis, reflecting antioxidant-poor and -rich diet. Morover, we have screened 1000 students in one school for schistosomiasis, liver fibrosis (ultrasonography), hepatitis B and serum assays for total antioxidants, planning for an interventional RCT with Moringa-based diet compared to a placebo diet. All practical preparations and training of support staff have been done for such a trial, but the trial itself has not been financed, despite 13 applications for funding to Helse SO and Norwegian Research Council during these 5 years. The Project has, however, brought considerable light to the relation between antioxidant foods and parasitic liver fibrosis, which is an interesting topic for further studies. The Ethiopian Health Services have got an impetus to continue the focus on importance of antioxidant foods, even though the more convincing results of a randomised controlled trial with the Moringa stenopetala leave based diet has not been fulfilled. Ethiopian Development Research Institute, a national leader on research and innovation, has taken interest to follow up the innovation potential of Moringa stenopetala in Ethiopia
2014
Since the PhD project has no support for doing the major intervention project which was applied for, and since additional funding for this has not been funded despite annual applications to HSØ, NRC and other donors, the Post-doc student has focused on pilot projects to show feasibility of the study and preparatory activities1) We have established additional plant nursery and planted 600 seeds of selected type of Moringastenopetala in Haromsa and Kebele-02 schools in Kemisse which will be used as supplementary source for Moringafor the school based dietary supplement in the RCT which will be conducted starting March 2015. 2) We have carried parasitological, clinical, serological andultrasonographic examinations of 1562 schoolchildren in Haromsa, Kebele-02 and Chekorsoschools.Students from the first two schools will be randomized to receive praziquantel therapy with either Moringa based dietary supplement or control diet with poor antioxidant content while the third school will serve as non-intervention control group. The aim is to study is to assess the role of Moringa based diet in the prevention and reversal of schistosomal PPF compared to control groups. For these study cohorts, measurements of baseline total serum antioxidants, liver function tests and tests for HBsAg and anti-HCV has also been completed. 3) We have purchased the necessary food serving utensils, chairs and food staff such as wheat flour, cooking oil,etc that would be used in school based feeding centers. 4) We have trained 16 local support staff in Haromsa and Kebele-02 schools in on preparation of the preferred interventional diet to be used in the clinical trial. Furthermore, we have stocked dried Moringa leaves procured from suppliers from Arbamicharrangements have been done for the continued supply of Moringastenopetala leaves and spices to be used in the preparation of interventional diet. 5) We have employed five support staff, one junior lab technologist and one administrator to work for the school based RTC in Haromsa and Kebele-02 schools in Kemisse. 6) We have initiated a “multidisciplinary research on causes of liver diseases and treatment of hepatitis B in resource-limited settings- a pilot program in Ethiopia” which will be led by Dr.AsgeirJohannessen from Ullucal Centre for Imported and Tropical Diseases (UCITD) and Dr.NegaBerhe, from Aklilu Lemma Institute of Pathobiology, Addis Ababa University (ALIPB-AAU)in collaboration with St.Paul’s Millennium Teaching hospital in Addis Ababa and Haromaya University hospital in Harrar. 7) We have employed two nurses and two senior laboratory technicians who will be serving in the research project entitled “Multidisciplinary research on causes of liver diseases and treatment of hepatitis B in resource-limited settings- a pilot program in Ethiopia” 8) We have purchased HBV test kits, automated ELISA reader, clinical photometer and fibroscan through the research project entitled “Multidisciplinary research on causes of liver diseases and treatment of hepatitis B in resource-limited settings- a pilot program in Ethiopia”
2013
Schistosomiasis is one of the most important parasitic diseases in the world. Development of liver fibrosis is one of its major complications. Kowledge about mechanisms of liver fibrosis is limited. Some studies indicate that nutritional factors could be important.In this translational study we analyse antioxidant levels of Ethiopian foods and patient samples in the Nutrition Institute of University of Oslo and plan an RCT on the effects of diet based antioxidant supplementation. We also follow up cohorts of individuals with liver fibrosis since 2002. Research/Work Accomplishments in 2013: 1) We have established plant nursery and planted 550 seeds of selected type of Moringa stenopetala in Kemisse which will be distributed to families with schistosomal PPF who will be assigned to take Moringa based dietary supplement in the RCT planned to be stared in February 2014. 2) We have identified school based study cohort 400 subjects in two communities in Kemisse and Cheretee. One school cohort will receive the Moringa based dietary supplement and the other cohort will be on control diet supplement. The aim is to study the role of Moringa based diet in the prevention of schistosomal PPF compared to control group. For these study cohorts, measurements of baseline total serum antioxidants, ultrasonographic, anthropometric and parasitological study has been completed. 3) We have purchased the necessary food processing and cooking equipment and have also established feeding centers in Kemisse and Cheretee for the RTC study to be started in February 2014. 4) We have continued the training of 25 local support staff in Kemisse and Cheretee on preparation of the preferred interventional diet to be used in the clinical trial. Furthermore, we have started to stock dried Moringa leaves procured frome suppliers from Arbamich arrangements have been done for the continued supply of Moringa stenopetala leaves and spices to be used in the preparation of interventional diet. 5) We have employed a one nurse nutritionist, one junior lab technologist and a lab-assistant to work for the RTC based study in Kemisse and Cheretee 6) Seminars: “Studies on Schistosomal liver fibrosis in Ethiopia” presented ALIPB on 29 October 2013. 7) Recruitment of PhD student: We have recruited PhD student Filimon Mitiku who is employed by Addis Ababa University (AAU), ALIPB who will be working on serum antioxidant levels of study subjects in the RTC in relation to treatment outcome of schistosomal PPF over a two year period. He is currently developing his research proposal to be submitted to AAU where he will register as PhD student. He may need to take supplemental course works in Norway if deemed necessary.
2012
Schistosomiasis is one of the most important parasitic diseases in the world. Development of liver fibrosis is one if its major complications. Knowledge about the mechanisms of liver fibrosis is limited. some studies indicate that nutritional facators could be importantThis study is a translational study doing 1) antioxidant anslyses of Ethiopian foods and patient samples in the Nutrition Institute, Univ. of Oslo 2) and RCT on the effects of diet based antioxidant supplementation and 3) followup on cohorts with fibrosis in areas with antioxidant deficient food intake in North Ethiopia since 2002. Research accomplishments in 2012: 1)We have accomplished recruitment of 500subjects with schistosomal periportal fibrosis for antioxidant rich diet based randomized clinical trial to be started in February 2013. Baseline laboratory tests for serum antioxidants, liver enzymes, platelet counts and hyaluronic acid levels have been completed. Furthermore, detailed anthropometric measurements, stool examinations, determination of intensity of S.mansoni infections has been completed 2)Following dietary assays done at the Nutrition Institute, UIO and at Aklilu Lemma Institute of pathobiology we have determined the specific components of the anti-oxidant rich interventional study diet and control diet to be used in the clinical trial. Furthermore, we have conducted assessment of acceptability of the preferred interventional study diet in Kemisse and Cheretee which was rated as very good. 3)We have trained 20 local support staff in Kemisse and Cheretee on preparation of the preferred interventional diet to be used in the clinical trial. Furthermore, arrangements have been done for the continued supply of Moringa stenopetala leaves and spices to be used in the preparation of interventional diet.
2011
Schistosomiasis is one of the most important parasitic diseases in the world. Development of liver fibrosis is one of its major complications. Knowledge about the mechanisms of liver fibrosis is limited. Some studies indicate that nutritional factors could be important.This project is a translational study doing 1) antioxidant analyses of Ethiopian foods and patient samples in the Nutrition Institute, Univ. of Oslo 2) an RCT on the effects of diet based antioxidant supplementation and 3) follow-up on cohorts with fibrosis in areas with different antioxidant food intake in South- and North Ethiopia annually from 2002. Research Accomplishments in 2011: 1)Assay for antioxidant content of 32 herbs, vegetables and cereals commonly consumed in communities with very low levels of schistosomal periportal fibrosis despite having high levels of S. mansoni infections were performed in the Nutrition Institute, Oslo University and at Aklilu Lemma Institute of Pathobiology, Addis Ababa University. Based on these, we have identified some of the herbs such as Clove, Basil and Thyme and leaves of Moringa Stenopetala to have very high content of antioxidants which will be used in our dietary intervention study. 2)We have screened a total of 5324 with stool examination and ultrasonographic examination of the liver to recruit the required 414 subjects with schistosomal periportal fibrosis (PPF) which will be randomized into three groups for antioxidant rich dietary supplementation study in the Kemise area of North Ethiopia. To accommodate for possible defaulters, we plan to recruit an additional 10% (about 42 subjects with PPF) in the coming two months of field surveys. Besides parasitological examinations, we have completed baseline anthropometric assessment and determination of serum antioxidant levels for the 414 subjects with PPF. 3)In 2011, we managed to trace and re-evaluate our student morbidity cohort established in 2002, (145 of 159 in Worke-Mado of North Ethiopia and 120 of 161 student cohort in Sille of South Ethiopia). At base line the two villages had comparable levels of S. mansoni infection. Over a period of 9 years, subjects in Worke-mado, who have poor access to antioxidant rich fruits and vegetables developed significantly more schistosomal periportal fibrosis (PPF) compared to Sille, where antioxidant foods are abundantly available. 4)Using project fund, we have purchased the necessary laboratory equipment for antioxidant assays in serum and food items using the FRAP assay. To this effect, we had a successful transfer of laboratory technology with trainer from Oslo University in the FRAP assay. 5)Furthermore, from November 3 – December 2, our research project has provided research base with financial and technical support for field works in Sille, Workemado and Cherettee to MSc student Nina Glarum from Agder University, Norway and MSc student Elsa Hagos from Aklilu Lemma Institute of Pathobiology. Their research title is “ A study on knowledge, attitude and acceptability of M. stenopetala based dishes in Worke-mado and Cheretee community in Northern Ethiopia” . This fieldwork were supportive for the transfer of an acceptable antioxidant rich diet from South- to North Ethiopia for the intervention in our RCT.
2010
Schistosomais er en av verdens viktigste parasittsykdommer. Bindevevsdannelse i leveren er dens viktigste komplikasjon. Det er liten kunnskap om mekanismene for disse leverskadene. Nye studier antyder at ernæringsfaktorer kan ha betydning.Det aktuelle prosjektet er en translasjonsstudie, som kombinerer basalforskning ved Ernærings-instituttet ved Universitetet i Oslo om antioksidant-relatert bindevevsdannelse med kliniske studier i Etiopia: I tillegg til en oppfølgingsstudie av tidligere ultralyd-undersøkte skoleelever med lever-schistosomiasis i nord- og sør-Etiopia, vil en gjennomføre en blindet intervensjonsstudie blant tilfeldig utvalgte individer med slik skade. Alle vil motta WHO-standard parasittbehandling. To grupper vil i tillegg motta hver sin dosering av et ernæringskonsentrat basert på lokale antioksydant-rike krydder og grønnsaker, mens en tredje gruppe ikke vil motta noe slikt tilskudd. Kontrollgruppen kan forsvares etisk med at ingen vet om tilskuddet vil ha effect. En vil samtidig kartlegge kosthold på individnivå. I løpet av 2010 har kohorten av skoleelever blitt undersøkt for 9. år på rad. Kompetanse og teknologi for antioksidant-screening av matvarer og pasientprøver er overført fra Ernæringsinstituttet i Oslo til Aklilu Lemma Institute of pathobiology i Addis Ababa. Kartlegging av kostholdet pågår, og det er samlet inn aktuelle matvarer for antioksidant-analyser og sammensetning av ernæringskonsentratet for intervensjonsstudien. Landsbyene i intervensjonsområdet i nord-Etiopia er kartlagt ved folketelling, og hvert hushold screenes for tiden med ultralyd for leverfibrose, med tanke på inklusjon i studien. Det bygges opp et nettverk av helseagenter for overvåkning på hoshold- og landsbynivå og i løpet av 2011 er den store intervensjonsstudien planlagt startet.
Vitenskapelige artikler
Gashaw F, Aemero M, Legesse M, Petros B, Teklehaimanot T, Medhin G, Berhe N, Mekonnen Y, Erko B

Prevalence of intestinal helminth infection among school children in Maksegnit and Enfranz Towns, northwestern Ethiopia, with emphasis on Schistosoma mansoni infection.

Parasit Vectors 2015;8():567. Epub 2015 okt 31

PMID: 26520794

Aemero M, Boissier J, Climent D, Moné H, Mouahid G, Berhe N, Erko B

Genetic diversity, multiplicity of infection and population structure of Schistosoma mansoni isolates from human hosts in Ethiopia.

BMC Genet 2015;16():137. Epub 2015 des 3

PMID: 26630932

Aemero Mulugeta, Berhe Nega, Erko Berhanu

Status of schistosoma mansoni prevalence and intensity of infection in geographically apart endemic localities of ethiopia: a comparison.

Ethiop J Health Sci 2014 Jul;24(3):189-94.

PMID: 25183924

Mekonnen Seleshi Kebede, Aseffa Abraham, Berhe Nega, Teklehaymanot Tilahun, Clouse Ronald M, Gebru Tamirat, Medhin Girmay, Velavan Thirumalaisamy P

Return of chloroquine-sensitive Plasmodium falciparum parasites and emergence of chloroquine-resistant Plasmodium vivax in Ethiopia.

Malar J 2014;13():244. Epub 2014 jun 25

PMID: 24964730

Abebe Nigus, Erko Berhanu, Medhin Girmay, Berhe Nega

Clinico-epidemiological study of Schistosomiasis mansoni in Waja-Timuga, District of Alamata, northern Ethiopia.

Parasit Vectors 2014;7():158. Epub 2014 apr 1

PMID: 24690404

Mekonnen Seleshi Kebede, Aseffa Abraham, Medhin Girmay, Berhe Nega, Velavan Thirumalaisamy P

Re-evaluation of microscopy confirmed Plasmodium falciparum and Plasmodium vivax malaria by nested PCR detection in southern Ethiopia.

Malar J 2014;13():48. Epub 2014 feb 6

PMID: 24502664

Filimon Mitiku

Correlation of serum Hyaluronic acid with ultrasonographic patterns of schistosomalperiportal fibrosis in selected S. mansoni en

Master thesis AAU-ID.No GRS/2477/03

Elsa Hagos

Correlation of platelet index and liver enzymes with ultrasonographic patters of schistosomalperiportal fibrosis in selected S.

Master thesis AAU-ID.No GRS/2478/03

Nigus Abebe

Morbidity of Schistosomiasis in relation to intensity of infection in Waja-Timuga, Southern Tigray

Master thesis AAU-ID.No GRS/0528/03

Nina Glarum

Usage and acceptability of Moringa stenopetala in diet in Ethiopia

Master thesis Univ. i Agder ME 5011-1 2012

Amare Alemtsehay

Effect of (Kosso) Hagenia abyssinica in the treatment of Schistosoma mansoni infection

AAU-ID.No GSR/0537/02 (MSc Thesis)

Gebreselasse Gebremedhin

Association of total serum anti-oxidants with periportal fiibrosis and intensity of S. mansoni infection in Worke-mado, NE Eth

AAU-ID.No GSR/0892/02 (MSc Thesis)

Asmare Tigabie

Comparison of antioxidant content of diets consumed in communities with high and low prevalence of PPF

AAU-ID.No GSR/2228/02 (MSc Thesis)

Haileselasie Haftay

Assessment of the prevalence and intensity of S. mansoni infection an re-infection among school children in Mekele, N-Ethiopia

AAU-ID.No GSR/0895/02 (MSc Thesis)

Tedla Kiros

Association of total serum antioxidants with peri portal fibrosis and intensity of S. mansoni infection in Cheretee, NE Ethiopia

AAU-ID.No GSR/0998/02 (MSc Thesis)

Tafesse Nebiyo

Prevalence and risk factors of schistosomiasis and soil transmitted helminthes among pregnant mothers in North Shewa Z, Oromia

AAU-ID.No GSR/2225/02 (MSc Thesis)

Tigabu Addisu Tesfahun

Soil transmitted helminths and S. mansoni infections among school children in Libo-Kemkem District, NW Ethiopia

AAU-ID.No GSR/2227/02 (MSc Thesis)

Mekonnen Zelalem

Surveuy of S. mansoni infection among school children in Mekelle city, North Ethiopia

AAU-ID.No GSR/0900/02 (MSc Thesis)

Bireda Manyawkal

Intra and inter species variation of egg counts in the diagnosis of schisomiasis mansoni

AAU-ID.No GSR/0386/95 (MSc Thesis)

Doktorgrader
Mistire Wolde

A study on the association of Schistosoma mansoni infection with the occurrence of diabetes mellitus in Ethiopia

Disputert:
desember 2015
Hovedveileder:
Nega Berhe
Mebrate Dufera

Studies on the interactions and associations of schistosomal and malaria co-morbidities

Disputert:
desember 2015
Hovedveileder:
Nega Berhe
Mulugeta Aemera

Genetic Diversity, Multiplicity of Infection and Population Structure of Schistosoma mansoni Isolates of Ethiopia within Humans

Disputert:
november 2011
Hovedveileder:
Nega Berhe
Deltagere
  • Rune Blomhoff Medveileder
  • Bjørn Myrvang Medveileder
  • Svein Gunnar Gundersen Prosjektleder
  • Nega Berhe Postdoktorstipendiat
  • Elling Bere Forsker (annen finansiering)

eRapport er utarbeidet av Sølvi Lerfald og Reidar Thorstensen, Regionalt kompetansesenter for klinisk forskning, Helse Vest RHF, og videreutvikles av de fire RHF-ene i fellesskap, med støtte fra Helse Vest IKT

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