Ignite Creation Date:
2024-05-06 @ 6:51 PM
Last Modification Date:
2024-10-26 @ 2:56 PM
Study NCT ID:
NCT05818059
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-04-18
First Post:
2023-03-06
Brief Title:
Active Close Contact Investigation of Tuberculosis Through Computer-aided Detection and Stool Xpert MTBRIF Among People Living in Ethiopia
Sponsor:
Doctors with Africa - CUAMM
Organization:
Doctors with Africa - CUAMM
Study Overview
Official Title:
Active Close Contact Investigation of Tuberculosis Through Computer-aided Detection and Stool Xpert MTBRIF Among People Living in Oromia Region Ethiopia a Prospective Cross-sectional Study CADOOL Study
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CADOOL
Brief Summary:
Tuberculosis is the 13th cause of death from all causes infecting roughly the 25 of the world population and Ethiopia is listed among the 30 high-burden countries both for TB and for HIVTB In recent years the immediate consequence of the COVID-19 pandemic was a large fall in the number of newly reported TB cases indicators that represent a relevant drawback in the pursue of the 2025 End TB Milestones
For active case investigation of TB close contacts WHO recently recommended the use of Computer- aided detection CAD a technology that can help chest X-ray interpretation in situations of human resources constrains and it may be cost-effective in low-resource settings Also for tuberculosis diagnosis widely-available GeneXpert on stool samples showed high diagnostic performances in term of both sensitivity and specificity
It is important to assess alternative modalities that could improve diagnosis during TB contact investigation in Ethiopia and the other countries where TB represents a crucial burden
For active case investigation of TB close contacts WHO recently recommended the use of Computer- aided detection CAD a technology that can help chest X-ray interpretation in situations of human resources constrains and it may be cost-effective in low-resource settings Also for tuberculosis diagnosis widely-available GeneXpert on stool samples showed high diagnostic performances in term of both sensitivity and specificity
It is important to assess alternative modalities that could improve diagnosis during TB contact investigation in Ethiopia and the other countries where TB represents a crucial burden
Detailed Description:
Despite being a preventable and treatable disease TB infects roughly 25 of the world population causing an estimated 14 million deaths among HIV-negative people 95 uncertainty interval 13- 15 million and 187 000 deaths 95 UI 158 000-218 000 among people living with HIV Globally an estimated 106 million people fell ill with tuberculosis only in 2021 increasing from the 101 million cases estimated for 2020 thus reversing a long-lasting decreasing trend Tuberculosis is a disease of poverty as 87 of all incident cases of TB were registered in the 30 high-burden countries mainly low-income countries from WHO regions of South-East Asia and Africa At this regard the relationship between TB burden and commonly used indicators of underdevelopment is well established Widely recognized TB determinants include gross domestic product GDP and prevalence of undernourishment the latter alone being accountable for an estimated 2 million new TB cases in 2021 As reported by the World Health Organization the immediate consequence of the COVID-19 pandemic was a large fall in the number of newly reported TB cases and an estimated increase of incident cases of rifampicin-resistant TB all indicators that represent a relevant drawback in the pursue of the 2025 End TB Milestones These gap in TB diagnosis include both people who are diagnosed but not reported to local public health authorities and people who are not diagnosed and thus have not entered in care
For the diagnosis of active TB the gold standard technique remains seeking for microbiological evidence of infection This is classically done by sputum smear microscopy and liquid culture with drug susceptibility testing Culture is the gold standard for the diagnosis but its use however is hampered by the fact that results are available only after 10-21 days and is thus of little or no help in clinical decision-making Since its endorsement by the WHO guidelines in 2010 Xpert MTBRIF Cepheid CA USA a molecular test that can detect mycobacterial DNA and genetic polymorphisms associated with rifampicin resistance has entered into diagnostic workup in both high- and low-income countries A new version of the test has been approved by WHO in 2021 Xpert MTBRIF Ultra with a sensitivity approaching the one recorded for culture assays but with the advantage like its predecessor of requiring fewer resources and delivering faster results Along with microbiological testing detection of radiological abnormalities through chest X-ray has recently gained a lot of attention and it is now recommended as the standard screening test A more detailed description of the diagnostic performances of chest X-ray and digital chest X-ray with computer-aided detection is provided in the next paragraph of this introduction
In recent years computer-aided detection CAD are artificial- intelligence based software that have been developed with the aim to offer automated interpretation of digital CXR images In broad terms CAD programs produce a numerical score that interpret CXR alterations in order to quantify the probability of TB When diagnostic accuracy is assessed against bacteriologically confirmed TB CAD software sensitivity ranges from 90 to 92 and specificity ranges from 23 to 66 fulfilling thus the minimal sensitivity required by WHO for a screening test These diagnostic performances were confirmed by several prospective studies conducted in low- and middle-income countries LMIC systematic reviews and one patient-level meta-analysis thus leading to the endorsement of CAD technologies by current WHO consolidated TB guidelines for the screening of individuals aged 15 years or older belonging to selected high-risk populations Among the CAD software packages commercially available CAD4TB platform version 6 Delft Imaging Systems The Netherlands developed using deep-learning technologies - a type of machine learning technology based on artificial neural networks - releases results in few seconds and was designed to work on patients from 4 years of age In a recent study conducted when compared to a microbiological Xpert reference standard CAD4TB v7 has been shown to have both high efficiency and be cost-effective in high-burden settings being able to process 132 images per day at the cost of less than 6 USD per person Even if the technology is validated for the use in individuals aged 4 years or older very few data exist on the clinical utility of this technology among childrenIn recent years attention has been attracted by Xpert MTBRIF on stool samples since mycobacteria- containing sputum may be swallowed and then be available for molecular testing Similarly to Xpert on sputum samples stool Xpert is able to detect both the presence of mycobacterial DNA and mutations associated with rifampin resistance The use of Xpert MTBRIF on stool samples has been introduced in the 2020 WHO guidelines as a possible initial diagnostic test for children with signs and symptoms of pulmonary TB However this recommendation is based on low certainty of evidence Due to lack of available evidence no recommendation has been issued so far about the use of Xpert on stool samples in the adult population
Ethiopia is listed among the 30 high-burden countries both for TB and for HIVTB transitioning out in the last Global Tuberculosis Report from the list of the high-burden countries for multidrug- resistant or rifampicin resistant TB MDR-RRTB Annual TB incidence is 132 cases per 100000 people 95CI 92-178 with a case-fatality ratio of 15 and most of the cases attributable to undernourishment Disease incidence and mortality in both HIV-positive and HIV-uninfected people is reducing almost attaining the End TB milestone of a 35 reduction in TB deaths compared to 2015 However since the pandemic-related disruption on TB services impacted the number of newly diagnosed TB cases its influence on mortality and overall disease burden is likely yet to be seen
As in most of low-resources high-burden countries provider-initiated contact investigation is rarely carried out in Ethiopia although contact tracing and evaluation of all persons who have been incontact with an active case of TB is recommended by the latest National Guidelines The World Health Organization recently updated its screening guidelines putting emphasis on the importance of the importance of active provider-initiated screening of at-risk populations especially households of index TB patients Epidemiological data about active TB among household contacts are limited but when reported prevalence rates are high Also a meta-analysis conducted by Gamtesa et al found that healthcare-seeking behavior in Ethiopia is low even in patients with showing signs and symptoms of TB
Provider-initiated screening of selected high-risk populations is a key strategy in the fight towards TB eradication According to WHO this approach should entail systematic identification of people with possible TB disease with tests examinations or other procedures that can be applied rapidly In this context data about the clinical impact of the use of CAD technologies in Ethiopia are lacking Also data about diagnostic performances of respectively CAD software and stool Xpert MTBRIF in the pediatric population and adult population are needed
The study will be carried out in at St Luke Catholic Hospital Wolisso in Ethiopia
St Luke Catholic Hospital is the referral Hospital in Southwest Shoa zone Oromia Region between Addis Ababa and Jimma covering 400km distance St Luke Catholic Hospital serves a population from a catchment area of roughly 14 million people As of today the hospital bed capacity is 208 while mean outpatient department visits are 350 patients per day
For the year 2021 in St Luke Hospital 207 patients were diagnosed with pulmonary TB Of those 164 patients were treated as inpatients and 43 were treated as outpatients Out of these 5 showed Rifampicin resistance These MDR cases were referred to the Therapeutic Initiating Centres for second line treatment Among patients treated in OPD clinic 30 were followed into the hospital TB clinic
Routine TB screening in St Luke Catholic Hospital is based on patient-initiated pathway with assessment of signs and symptoms suggestive of TB Possible TB cases are identified through a clinical visit that may include chest X-ray evaluation When performed chest X-ray images are evaluated by on-duty clinicians in digital format
For the diagnosis of active TB the gold standard technique remains seeking for microbiological evidence of infection This is classically done by sputum smear microscopy and liquid culture with drug susceptibility testing Culture is the gold standard for the diagnosis but its use however is hampered by the fact that results are available only after 10-21 days and is thus of little or no help in clinical decision-making Since its endorsement by the WHO guidelines in 2010 Xpert MTBRIF Cepheid CA USA a molecular test that can detect mycobacterial DNA and genetic polymorphisms associated with rifampicin resistance has entered into diagnostic workup in both high- and low-income countries A new version of the test has been approved by WHO in 2021 Xpert MTBRIF Ultra with a sensitivity approaching the one recorded for culture assays but with the advantage like its predecessor of requiring fewer resources and delivering faster results Along with microbiological testing detection of radiological abnormalities through chest X-ray has recently gained a lot of attention and it is now recommended as the standard screening test A more detailed description of the diagnostic performances of chest X-ray and digital chest X-ray with computer-aided detection is provided in the next paragraph of this introduction
In recent years computer-aided detection CAD are artificial- intelligence based software that have been developed with the aim to offer automated interpretation of digital CXR images In broad terms CAD programs produce a numerical score that interpret CXR alterations in order to quantify the probability of TB When diagnostic accuracy is assessed against bacteriologically confirmed TB CAD software sensitivity ranges from 90 to 92 and specificity ranges from 23 to 66 fulfilling thus the minimal sensitivity required by WHO for a screening test These diagnostic performances were confirmed by several prospective studies conducted in low- and middle-income countries LMIC systematic reviews and one patient-level meta-analysis thus leading to the endorsement of CAD technologies by current WHO consolidated TB guidelines for the screening of individuals aged 15 years or older belonging to selected high-risk populations Among the CAD software packages commercially available CAD4TB platform version 6 Delft Imaging Systems The Netherlands developed using deep-learning technologies - a type of machine learning technology based on artificial neural networks - releases results in few seconds and was designed to work on patients from 4 years of age In a recent study conducted when compared to a microbiological Xpert reference standard CAD4TB v7 has been shown to have both high efficiency and be cost-effective in high-burden settings being able to process 132 images per day at the cost of less than 6 USD per person Even if the technology is validated for the use in individuals aged 4 years or older very few data exist on the clinical utility of this technology among childrenIn recent years attention has been attracted by Xpert MTBRIF on stool samples since mycobacteria- containing sputum may be swallowed and then be available for molecular testing Similarly to Xpert on sputum samples stool Xpert is able to detect both the presence of mycobacterial DNA and mutations associated with rifampin resistance The use of Xpert MTBRIF on stool samples has been introduced in the 2020 WHO guidelines as a possible initial diagnostic test for children with signs and symptoms of pulmonary TB However this recommendation is based on low certainty of evidence Due to lack of available evidence no recommendation has been issued so far about the use of Xpert on stool samples in the adult population
Ethiopia is listed among the 30 high-burden countries both for TB and for HIVTB transitioning out in the last Global Tuberculosis Report from the list of the high-burden countries for multidrug- resistant or rifampicin resistant TB MDR-RRTB Annual TB incidence is 132 cases per 100000 people 95CI 92-178 with a case-fatality ratio of 15 and most of the cases attributable to undernourishment Disease incidence and mortality in both HIV-positive and HIV-uninfected people is reducing almost attaining the End TB milestone of a 35 reduction in TB deaths compared to 2015 However since the pandemic-related disruption on TB services impacted the number of newly diagnosed TB cases its influence on mortality and overall disease burden is likely yet to be seen
As in most of low-resources high-burden countries provider-initiated contact investigation is rarely carried out in Ethiopia although contact tracing and evaluation of all persons who have been incontact with an active case of TB is recommended by the latest National Guidelines The World Health Organization recently updated its screening guidelines putting emphasis on the importance of the importance of active provider-initiated screening of at-risk populations especially households of index TB patients Epidemiological data about active TB among household contacts are limited but when reported prevalence rates are high Also a meta-analysis conducted by Gamtesa et al found that healthcare-seeking behavior in Ethiopia is low even in patients with showing signs and symptoms of TB
Provider-initiated screening of selected high-risk populations is a key strategy in the fight towards TB eradication According to WHO this approach should entail systematic identification of people with possible TB disease with tests examinations or other procedures that can be applied rapidly In this context data about the clinical impact of the use of CAD technologies in Ethiopia are lacking Also data about diagnostic performances of respectively CAD software and stool Xpert MTBRIF in the pediatric population and adult population are needed
The study will be carried out in at St Luke Catholic Hospital Wolisso in Ethiopia
St Luke Catholic Hospital is the referral Hospital in Southwest Shoa zone Oromia Region between Addis Ababa and Jimma covering 400km distance St Luke Catholic Hospital serves a population from a catchment area of roughly 14 million people As of today the hospital bed capacity is 208 while mean outpatient department visits are 350 patients per day
For the year 2021 in St Luke Hospital 207 patients were diagnosed with pulmonary TB Of those 164 patients were treated as inpatients and 43 were treated as outpatients Out of these 5 showed Rifampicin resistance These MDR cases were referred to the Therapeutic Initiating Centres for second line treatment Among patients treated in OPD clinic 30 were followed into the hospital TB clinic
Routine TB screening in St Luke Catholic Hospital is based on patient-initiated pathway with assessment of signs and symptoms suggestive of TB Possible TB cases are identified through a clinical visit that may include chest X-ray evaluation When performed chest X-ray images are evaluated by on-duty clinicians in digital format
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None