Improved diagnosis of tuberculosis by antigen detection from sputum and extrapulmonary samples using immunochemistry-based assays
Prosjekt
- Prosjektnummer
- 911886
- Ansvarlig person
- Tehmina Mustafa
- Institusjon
- Helse Bergen HF
- Prosjektkategori
- Åpen prosjektstøtte
- Helsekategori
- Infection
- Forskningsaktivitet
- 4. Detection and Diagnosis
Rapporter
Tuberculosis, a potentially curable disease, kills 1.4 million young and economically productive people annually. Lack of better diagnostic tools leads to many undiagnosed and untreated cases causing increased mortality. University of Bergen has developed a new and better method to diagnose tuberculosis which can save many lives.In Norway the incidence of tuberculosis (TB) is relatively low, however a steady increase in new TB cases has been observed in recent years. The routinely used diagnostic methods fail to detect all TB cases leading to increased morbidity and mortality. We have developed a rapid, robust, sensitive and specific method to diagnose TB from various patient samples including fluids, aspirates and biopsies. The method is significantly better than the routine methods. Lower costs and robustness makes it suitable for implementation in TB endemic countries. The main objective of this study is to further improve the assay and implement and validate the assay in the routine diagnostic settings in high- (Zanzibar) and low- (Norway) TB endemic countries. Mnazi Mmoja Hospital (MMH) at Zanzibar and Haukeland University Hospital in Norway were selected as study sites. The assay has been performed in addition to the routine diagnostic work-up for TB. Detailed clinical information, data on patient knowledge, health- seeking behavior and economic burden has been collected by using a structured questionnaire. Data analysis on clinical information, validation of the test, feasibility of implementation, and diagnostic delay from Zanzibar has been completed, and write-up of results is ongoing. Two manuscripts have submitted for publication, and are under peer- review, and two manuscripts are in preparation for publication in the international peer-reviewed journals. The results from Zanzibar show that the new test is feasible to implement and has significantly higher sensitivity and specificity as compared to the routine tests. However sustainability of the test faces challenges due to economic constrains. Data from Norway has not been analysed yet.
Reference to the progress report 2016, following is a summary of the activities performed in 2017:
Activities in Norway:
1.The work on the improvement of the diagnostic test by development of a monoclonal and a new polyclonal antibody has been done in 2017.
2.Data analysis on the study of biomarkers for monitoring response to treatment in extrapulmonary TB on the samples collected from Zanzibar has been done. The results were presented as oral presentation at the European Respiratory Kongress, 2017, Milan, Italy.
Delays from the planned activities:
1.Data analysis of the work on implementation of the test in Norway and development of the test for sputum, has been delayed because the PhD candidate who is working with this dataset (funded through Research Council of Norway), has been on maternity leave since April 2017.
2.The PhD fellowship for Melissa Jørstad (Project number 911849) has been extended till Feb 2018 through research funding from the Department of Thoracic Medicine, Haukeland University Hospital, to complete the PhD thesis.
3.The bioengineer at Haukeland University Hospital got extension of the position till December 2017 due to the extension of research activities in Norway.
The delays in the planned activities have had no negative consequences.
brukermedvirkning er ikke relevant for prosjektet.
Tuberculosis, a potentially curable disease, kills 1.4 million young and economically productive people annually. Lack of better diagnostic tools leads to many undiagnosed and untreated cases causing increased mortality. University of Bergen has developed a new and better method to diagnose tuberculosis which can save many lives.In Norway the incidence of tuberculosis (TB) is relatively low, however a steady increase in new TB cases has been observed in recent years. The routinely used diagnostic methods fail to detect all TB cases leading to increased morbidity and mortality. We have developed a rapid, robust, sensitive and specific method to diagnose TB from various patient samples including fluids, aspirates and biopsies. The method is significantly better than the routine methods. Lower costs and robustness makes it suitable for implementation in TB endemic countries. The main objective of this study is to further improve the assay and implement and validate the assay in the routine diagnostic settings in high- (Zanzibar) and low- (Norway) TB endemic countries. Mnazi Mmoja Hospital (MMH) at Zanzibar and Haukeland University Hospital in Norway were selected as study sites. The assay has been performed in addition to the routine diagnostic work-up for TB. Detailed clinical information, data on patient knowledge, health- seeking behavior and economic burden has been collected by using a structured questionnaire. Data analysis is ongoing. The preliminary results from Zanzibar show that the new test is feasible to implement and has significantly higher sensitivity and specificity as compared to the routine tests. However sustainability of the test faces challenges due to economic constrains.
Reference to the progress report 2015, following is a summary of the activities performed in 2016:
Activities in Norway:
1. Finished one-year implementation of the new immunochemistry-based method on the routine patient samples from the Haukeland University Hospital, Stavanger university Hospital and Oslo University Hospital during spring and autumn of 2016. This data is being analysed by the PhD fellow. Furthermore the work on the improvement of the diagnostic test by development of a monoclonal antibody was done in 2016 and is still undergoing.
2. Nested-PCR was performed on the samples from Zanzibar to categorize the patients as the TB or non-TB for the purpose of validation.
3. Further work on the development of immunochemistry based antigen detection method on sputum has been performed. Protocols were developed, and the proof-of-principle has been established.
4. Biomarkers for monitoring response to treatment in extrapulmonary TB were studied on the samples collected from Zanzibar.
Activities in Zanzibar:
1. Follow-up of the patient cohort was completed, and data analysis was started.
2. Sustainability of the new test in the routine diagnostics was assessed by the PhD candidate by field visits.
3. Data on feasibility of implementation was collected by PhD candidate by semi-structured interviews of local medical personnel at MMH.
4. Collection of sputum samples and relevant patient information was done for the development of a immunochemistry based antigen detection method on sputum.
Delays from the planned activities:
The PhD fellowship for Melissa Jørstad (Project number 911849) was started from 15.03.14, and leave was taken from 01.03.15- 31.05.15 with the corresponding prolongation of position till 14.06.17.
The bioengineer at Haukeland University Hospital started from 24.09.14 with the corresponding prolongation of position till 23.09.17. The planned activities in Norway have been correspondingly postponed till 23.09.17.
The delays in the planned activities have had no negative consequences.
Tuberculosis, a potentially curable disease, kills 1.4 million young and economically productive people annually. Lack of better diagnostic tools leads to many undiagnosed and untreated cases causing increased mortality. University of Bergen has developed a new and better method to diagnose tuberculosis which can save many lives.In Norway the incidence of tuberculosis (TB) is relatively low, however a steady increase in new TB cases has been observed in recent years. The routinely used diagnostic methods fail to detect many TB cases leading to increased morbidity and mortality. We have developed a rapid, robust, sensitive and specific method to diagnose TB from various patient samples including fluids, aspirates and biopsies. The method is significantly better than the routine methods. Lower costs and robustness makes it suitable for implementation in TB endemic countries. The main objective is to further improve the assay and implement and validate the assay in the routine diagnostic settings in high- (Zanzibar) and low- (Norway) TB endemic countries. Mnazi Mmoja Hospital at Zanzibar and Haukeland University Hospital in Norway are selected as study sites. The assay is performed in addition to the routine diagnostic work-up for TB. Feasibility of implementation, and cost effectiveness analysis will be performed.
Reference to the progress report 2014, following is a summary on the activities performed in 2015:
Activities in Norway:
1. Relevant patient samples with the suspicion of tuberculosis sent to the Laboratory of Microbiology and Laboratory of Pathology, Haukeland University Hospital, between Jannuary- December 2015, were included in the project. Furthermore patient samples were sent from Stavanger University Hospital and Oslo University Hospital. A system is developed to receive, and store the material & information according to the regulations & the project protocol. The new diagnostic test was performed on about 470 samples. The inclusion of samples from Oslo University Hospital will continue till autumn 2016. The test will be compared with the PCR-method.
2. Started work on the development of immunochemistry based antigen detection method on sputum. Protocols for the modification of various in-house antibodies are developed, and initial experiments are performed to establish the proof-of-principle.
Activities in Zanzibar:
1. Implementation of the new immunochemistry-based method in the routine Pathology laboratory at Mnazi Mmoja Hospital was done, and patient inclusion was completed. 132 patients have been included, and this cohort is followed-up for 6 months. Each patient was interviewed by using a detailed questionnaire, and the test was performed on the samples (reference to the report from the PhD candidate Melissa Jørstad). Quality control of the test was performed by Tehmina Mustafa and Lisbet Sviland. Furthermore qualitative data on the feasibility of implementation of the test has been collected by PhD candidate Melissa Jørstad by participatory observation.
2. Collection and storage of material for biobank as described in the Project.
3. Collection of sputum samples and relevant patient information for the development of a immunochemistry based antigen detection method on sputum.
Delays from the planned activities:
The PhD fellowship for Melissa Jørstad (Project number 911849) was started from 15.03.14, and leave was taken from 01.03.15- 31.05.15 with the corresponding prolongation of position till 14.06.17.
The bioengineer at Haukeland University Hospital started working on the project from 24.09.14 with the corresponding prolongation of position till 23.09.17. The planned activities in Norway have been correspondingly postponed till 23.09.17.
The delays in the planned activities have had no negative consequences.
Tuberculosis, a potentially curable disease, kills 1.4 million young and economically productive people annually. Lack of better diagnostic tools leads to many undiagnosed and untreated cases causing increased mortality. University of Bergen has developed a new and better method to diagnose tuberculosis which can save many lives.In Norway the incidence of tuberculosis (TB) is relatively low, however a steady increase in new TB cases has been observed in recent years. The routinely used diagnostic methods fail to detect many TB cases leading to increased morbidity and mortality. We have developed a rapid, robust, sensitive and specific method to diagnose TB from various patient samples including fluids, aspirates and biopsies. The method is significantly better than the routine methods. Lower costs and robustness makes it suitable for implementation in TB endemic countries. The main objective is to further improve the assay and implement and validate the assay in the routine diagnostic settings in high- (Zanzibar) and low- (Norway) TB endemic countries. Mnazi Mmoja Hospital at Zanzibar and Haukeland University Hospital in Norway are selected as study sites. The assay is performed in addition to the routine diagnostic work-up for TB. Feasibility of implementation, and cost effectiveness analysis will be performed.
Research activities and results achieved in the 2014 are summarized as follows:
January- March 2014:
•Development of questionnaires, consent forms and research protocols
•Ethical clearance from Norway (REKVest)
April-June 2014:
•Translation of questionnaire from English to Kiswahili.
•Visit to the Mnazi Mmoja Hospital for networking & collaboration between different departments
•Pre-testing and local adaptation of the questionnaire
•Introductory visits to the Stavanger and Oslo University Hospitals
July- August 2014:
•Establishment of routines and development of protocols
•Ethical clearance from the Research Ethics Committee of Zanzibar
•Training of the laboratory personnel at the Mnazi Mmoja hospital
•Hiring and training of the local clinical staff at Mnazi Mmoja Hospital
September2014- Jan 2015:
Activities in Zanzibar:
•Started inclusion of patients, including clinical history, physical examination, & detailed interview by using the questionnaire
•73 patients are included in the project so far
•Implementation of the new test in routine diagnostics. Personnel at the histopathology laboratory are running the new assay without supervision
•Supervision and Quality control by visits of supervisors to Mnazi Mmoja Hospital
•Follow-up of patients
•Collection and storage of material for biobank as described in the project
Activities in Norway:
•Hired bioengineer in 50% position
•Performed pilot experiments to establish routines for performance of the test on routinely collected samples.
•A PhD fellow financed by the Research Council of Norway is included in the project.
Delays from the planned activities:
Due to necessity of collaboration between several departments and hospitals, development of routines has taken longer than what was anticipated at the time of project planning. The process of hiring the personnel has also taken longer than anticipated. The PhD fellowship was started from 15.03.14, and the bioengineer at Haukeland Hospital started from 24.09.14. These delays would only postpone the planned activities without anyother negative consequences.
The inclusion of patients at Zanzibar has been slower than expected. Many patients are not referred to Mnazi Mmoja Hospital and treated outside this hospital. Our survey during the project planning did not reveal this situation. This challenge has been overcome by obtaining permission from the Ethical Committee of Zanzibar to include patients from peripheral hospitals.
Vitenskapelige artikler
Jørstad MD, Abdalla MA, Marijani M, Dyrhol-Riise AM, Sviland L, Mustafa, T
Improved diagnosis of extra pulmonary TB by antigen detection in extra pulmonary samples by immunochemistry-based assay
Conferenec abstract & poster
Deltagere
- Harald G Wiker Prosjektdeltaker
- Heidi Syre Carriere Prosjektdeltaker
- Edith Marianne Fick Prosjektdeltaker
- Anne Margarita Dyrhol Riise Medveileder
- Lisbeth Sviland Medveileder
- Melissa Davidsen Jørstad Ph.d.-kandidat
- Tehmina Mustafa Prosjektleder
- Ida Marie Hoel Ph.d.-kandidat
- Wahida Mohammed Jecha Prosjektdeltaker
- Abdalla Yussuf Mohammed Prosjektdeltaker
- Ranja Christiansen Prosjektdeltaker
- msafiri Marijani Prosjektdeltaker
- Maryam Abdalla Ali Prosjektdeltaker
- Abdalla Ysuf Mohammed Prosjektdeltaker
- Hasnu Makame Mwazini Prosjektdeltaker
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
Alle henvendelser rettes til Faglig rapportering, Helse Vest