Conference Material > Slide Presentation
Rapoud D, Cramer E, Al Asmar M, Sagara F, Ndiaye B, et al.
MSF Scientific Day International 2024. 16 May 2024; DOI:10.57740/2acXDPpuix
Conference Material > Abstract
Rapoud D, Cramer E, Al Asmar M, Sagara F, Ndiaye B, et al.
MSF Scientific Day International 2024. 16 May 2024; DOI:10.57740/rxwuURR8
INTRODUCTION
Antimicrobial resistance (AMR) is a major threat to public health and could cause 10 million deaths per year by 2050. Access to high-quality diagnostic tests is a key intervention to tackle AMR, leading to better patient care, provision of data for global surveillance, and more rational use of antibiotics. Despite technological advances, antimicrobial susceptibility testing (AST) interpretation is complex and requires expert clinical microbiologists, which are lacking in low- and middle-income countries (LMIC). To fill the gap, The Médecins Sans Frontières (MSF) Foundation developed Antibiogo, a smartphone-based application to support laboratory technicians with AST interpretation. We aimed to assess the clinical performance of Antibiogo in intended use settings as per European regulations for in-vitro diagnostic medical devices.
METHODS
Antibiogo combines image processing, machine learning, and expert system technologies for the provision of final results (S/I/R: Susceptible, Intermediate, or Resistant). In 2022, we assessed the clinical performance of Antibiogo according to European regulations in three microbiology laboratories in Jordan (MSF Reconstructive Surgery Hospital, Amman), Mali (MSF Paediatric Hospital, Koutiala), and Senegal (Pasteur Institute, Dakar). In each site, clinical AST performed for routine purposes was processed in parallel with Antibiogo. AST pictures and inhibition zone diameter values measured with Antibiogo were interpreted by an expert microbiologist who was masked to Antibiogo interpretation. We calculated S/I/R category agreement between the microbiologist and Antibiogo, as well as minor (mD), major (MD) and very major discrepancies (VMD).
RESULTS
We included 378 fresh isolates in the study, representing 11 different pathogens. The overall category agreement was 88.8% (95% CI 87.9–89.7), ranging per pathogen from 67.1% (63.2–70.8) (for Pseudomonas aeruginosa) to 98.1% (94.4–99.6) (for Haemophilus influenzae), with 10.2% (9.4–11.1) mD, 1.6% MD (1.2–2.3), and 0.25% VMD (0.08–0.59). From these results, Antibiogo was validated for 11 WHO priority pathogens. From an operational need identified, to proof of concept and evaluation, it became the first MSF CE-marked in-vitro diagnostic (IVD) test in May 2022. As of January 2024, it has been implemented in five MSF laboratories (in Central African Republic, Democratic Republic of the Congo, Jordan, Mali, and Yemen), and in public laboratories in Mali upon request from the Ministry of Health.
CONCLUSION
It will take 400 years to address the shortfall of microbiologists in LMIC at the present rate of training. In the meantime, technology can help fill the gap. In parallel to deployment of Antibiogo in additional countries and regions, developments are ongoing, and an improved version of the app will be released in 2024.
Antimicrobial resistance (AMR) is a major threat to public health and could cause 10 million deaths per year by 2050. Access to high-quality diagnostic tests is a key intervention to tackle AMR, leading to better patient care, provision of data for global surveillance, and more rational use of antibiotics. Despite technological advances, antimicrobial susceptibility testing (AST) interpretation is complex and requires expert clinical microbiologists, which are lacking in low- and middle-income countries (LMIC). To fill the gap, The Médecins Sans Frontières (MSF) Foundation developed Antibiogo, a smartphone-based application to support laboratory technicians with AST interpretation. We aimed to assess the clinical performance of Antibiogo in intended use settings as per European regulations for in-vitro diagnostic medical devices.
METHODS
Antibiogo combines image processing, machine learning, and expert system technologies for the provision of final results (S/I/R: Susceptible, Intermediate, or Resistant). In 2022, we assessed the clinical performance of Antibiogo according to European regulations in three microbiology laboratories in Jordan (MSF Reconstructive Surgery Hospital, Amman), Mali (MSF Paediatric Hospital, Koutiala), and Senegal (Pasteur Institute, Dakar). In each site, clinical AST performed for routine purposes was processed in parallel with Antibiogo. AST pictures and inhibition zone diameter values measured with Antibiogo were interpreted by an expert microbiologist who was masked to Antibiogo interpretation. We calculated S/I/R category agreement between the microbiologist and Antibiogo, as well as minor (mD), major (MD) and very major discrepancies (VMD).
RESULTS
We included 378 fresh isolates in the study, representing 11 different pathogens. The overall category agreement was 88.8% (95% CI 87.9–89.7), ranging per pathogen from 67.1% (63.2–70.8) (for Pseudomonas aeruginosa) to 98.1% (94.4–99.6) (for Haemophilus influenzae), with 10.2% (9.4–11.1) mD, 1.6% MD (1.2–2.3), and 0.25% VMD (0.08–0.59). From these results, Antibiogo was validated for 11 WHO priority pathogens. From an operational need identified, to proof of concept and evaluation, it became the first MSF CE-marked in-vitro diagnostic (IVD) test in May 2022. As of January 2024, it has been implemented in five MSF laboratories (in Central African Republic, Democratic Republic of the Congo, Jordan, Mali, and Yemen), and in public laboratories in Mali upon request from the Ministry of Health.
CONCLUSION
It will take 400 years to address the shortfall of microbiologists in LMIC at the present rate of training. In the meantime, technology can help fill the gap. In parallel to deployment of Antibiogo in additional countries and regions, developments are ongoing, and an improved version of the app will be released in 2024.
Journal Article > ResearchAbstract
N Engl J Med. 18 June 2020; Volume 382; 2397-2410.; DOI:10.1056/NEJMoa1910708
Blanc FX, Badje AD, Bonnet MMB, Gabillard D, Messou E, et al.
N Engl J Med. 18 June 2020; Volume 382; 2397-2410.; DOI:10.1056/NEJMoa1910708
BACKGROUND
In regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death.
METHODS
We conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter. Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization.
RESULTS
A total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses. At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). Serious adverse events were more common with systematic treatment.
CONCLUSIONS
Among severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events.
ClinicalTrials.gov number NCT02057796
In regions with high burdens of tuberculosis and human immunodeficiency virus (HIV), many HIV-infected adults begin antiretroviral therapy (ART) when they are already severely immunocompromised. Mortality after ART initiation is high in these patients, and tuberculosis and invasive bacterial diseases are common causes of death.
METHODS
We conducted a 48-week trial of empirical treatment for tuberculosis as compared with treatment guided by testing in HIV-infected adults who had not previously received ART and had CD4+ T-cell counts below 100 cells per cubic millimeter. Patients recruited in Ivory Coast, Uganda, Cambodia, and Vietnam were randomly assigned in a 1:1 ratio to undergo screening (Xpert MTB/RIF test, urinary lipoarabinomannan test, and chest radiography) to determine whether treatment for tuberculosis should be started or to receive systematic empirical treatment with rifampin, isoniazid, ethambutol, and pyrazinamide daily for 2 months, followed by rifampin and isoniazid daily for 4 months. The primary end point was a composite of death from any cause or invasive bacterial disease within 24 weeks (primary analysis) or within 48 weeks after randomization.
RESULTS
A total of 522 patients in the systematic-treatment group and 525 in the guided-treatment group were included in the analyses. At week 24, the rate of death from any cause or invasive bacterial disease (calculated as the number of first events per 100 patient-years) was 19.4 with systematic treatment and 20.3 with guided treatment (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.63 to 1.44). At week 48, the corresponding rates were 12.8 and 13.3 (adjusted hazard ratio, 0.97 [95% CI, 0.67 to 1.40]). At week 24, the probability of tuberculosis was lower with systematic treatment than with guided treatment (3.0% vs. 17.9%; adjusted hazard ratio, 0.15; 95% CI, 0.09 to 0.26), but the probability of grade 3 or 4 drug-related adverse events was higher with systematic treatment (17.4% vs. 7.2%; adjusted hazard ratio 2.57; 95% CI, 1.75 to 3.78). Serious adverse events were more common with systematic treatment.
CONCLUSIONS
Among severely immunosuppressed adults with HIV infection who had not previously received ART, systematic treatment for tuberculosis was not superior to test-guided treatment in reducing the rate of death or invasive bacterial disease over 24 or 48 weeks and was associated with more grade 3 or 4 adverse events.
ClinicalTrials.gov number NCT02057796