Conference Material > Abstract
Langendorf C, Nikolay B
Epicentre Scientific Day 2024. 23 May 2024
BACKGROUND
While case confirmation is most of the time not necessary for case management decisions– the measles outbreak response relies on the timely biological confirmation of outbreaks to facilitate a vaccination response. Seroprevalence estimates, on the other hand, can help plan vaccination activities or evaluate them, by quantifying immunization levels in the population. In remote areas where transport of serum or plasma samples is challenging, we ideally would like to use dried blood spots (DBS) which are easy to collect, easy to transport, and theoretically stable in time and temperature. However, the practical use of DBS under field conditions is not as easy as we expect. Based on different examples of measles surveys in the DRC and Niger, we will describe the challenges we are facing regarding interpretation of serology results from DBS for both measles
biological confirmation and seroprevalence surveys.
RESULTS AND DISCUSSION
In the DRC, for biological confirmation , the sensitivity of DBS samples compared to plasma decreases with transport delays and is lower in remote settings. Measles seroprevalence based on DBS was lower than expected, raising questions about the use of the recommended seropositivity threshold and the correlation with seroprotection after vaccination. In Niger, we found that a good quality DBS can be obtain under field conditions, and an adjustment factor for DBS compared to serum is needed but may vary between settings.
CONCLUSION
Serology on DBS is the most acceptable procedure so far for biological confirmation of measles cases and seroprevalence. However, additional investigations are needed to better standardize, test, and interpret DBS samples to help making the most appropriate operational decisions.
While case confirmation is most of the time not necessary for case management decisions– the measles outbreak response relies on the timely biological confirmation of outbreaks to facilitate a vaccination response. Seroprevalence estimates, on the other hand, can help plan vaccination activities or evaluate them, by quantifying immunization levels in the population. In remote areas where transport of serum or plasma samples is challenging, we ideally would like to use dried blood spots (DBS) which are easy to collect, easy to transport, and theoretically stable in time and temperature. However, the practical use of DBS under field conditions is not as easy as we expect. Based on different examples of measles surveys in the DRC and Niger, we will describe the challenges we are facing regarding interpretation of serology results from DBS for both measles
biological confirmation and seroprevalence surveys.
RESULTS AND DISCUSSION
In the DRC, for biological confirmation , the sensitivity of DBS samples compared to plasma decreases with transport delays and is lower in remote settings. Measles seroprevalence based on DBS was lower than expected, raising questions about the use of the recommended seropositivity threshold and the correlation with seroprotection after vaccination. In Niger, we found that a good quality DBS can be obtain under field conditions, and an adjustment factor for DBS compared to serum is needed but may vary between settings.
CONCLUSION
Serology on DBS is the most acceptable procedure so far for biological confirmation of measles cases and seroprevalence. However, additional investigations are needed to better standardize, test, and interpret DBS samples to help making the most appropriate operational decisions.
Journal Article > ReviewFull Text
Health Sci Rep. 4 January 2024; Volume 7 (Issue 1); e1794.; DOI:10.1002/hsr2.1794
Oduoye MO, Fatima E, Muzammil MA, Dave T, Irfan H, et al.
Health Sci Rep. 4 January 2024; Volume 7 (Issue 1); e1794.; DOI:10.1002/hsr2.1794
BACKGROUND AND AIMS
Artificial intelligence (AI) has emerged as a transformative force in laboratory medicine, promising significant advancements in healthcare delivery. This study explores the potential impact of AI on diagnostics and patient management within the context of laboratory medicine, with a particular focus on low‐ and middle‐income countries (LMICs).
METHODS
In writing this article, we conducted a thorough search of databases such as PubMed, ResearchGate, Web of Science, Scopus, and Google Scholar within 20 years. The study examines AI's capabilities, including learning, reasoning, and decision‐making, mirroring human cognitive processes. It highlights AI's adeptness at processing vast data sets, identifying patterns, and expediting the extraction of actionable insights, particularly in medical imaging interpretation and laboratory test data analysis. The research emphasizes the potential benefits of AI in early disease detection, therapeutic interventions, and personalized treatment strategies.
RESULTS
In the realm of laboratory medicine, AI demonstrates remarkable precision in interpreting medical images such as radiography, computed tomography, and magnetic resonance imaging. Its predictive analytical capabilities extend to forecasting patient trajectories and informing personalized treatment strategies using comprehensive data sets comprising clinical outcomes, patient records, and laboratory results. The study underscores the significance of AI in addressing healthcare challenges, especially in resource‐constrained LMICs.
CONCLUSION
While acknowledging the profound impact of AI on laboratory medicine in LMICs, the study recognizes challenges such as inadequate data availability, digital infrastructure deficiencies, and ethical considerations. Successful implementation necessitates substantial investments in digital infrastructure, the establishment of data‐sharing networks, and the formulation of regulatory frameworks. The study concludes that collaborative efforts among stakeholders, including international organizations, governments, and nongovernmental entities, are crucial for overcoming obstacles and responsibly integrating AI into laboratory medicine in LMICs. A comprehensive, coordinated approach is essential for realizing AI's transformative potential and advancing health care in LMICs.
Artificial intelligence (AI) has emerged as a transformative force in laboratory medicine, promising significant advancements in healthcare delivery. This study explores the potential impact of AI on diagnostics and patient management within the context of laboratory medicine, with a particular focus on low‐ and middle‐income countries (LMICs).
METHODS
In writing this article, we conducted a thorough search of databases such as PubMed, ResearchGate, Web of Science, Scopus, and Google Scholar within 20 years. The study examines AI's capabilities, including learning, reasoning, and decision‐making, mirroring human cognitive processes. It highlights AI's adeptness at processing vast data sets, identifying patterns, and expediting the extraction of actionable insights, particularly in medical imaging interpretation and laboratory test data analysis. The research emphasizes the potential benefits of AI in early disease detection, therapeutic interventions, and personalized treatment strategies.
RESULTS
In the realm of laboratory medicine, AI demonstrates remarkable precision in interpreting medical images such as radiography, computed tomography, and magnetic resonance imaging. Its predictive analytical capabilities extend to forecasting patient trajectories and informing personalized treatment strategies using comprehensive data sets comprising clinical outcomes, patient records, and laboratory results. The study underscores the significance of AI in addressing healthcare challenges, especially in resource‐constrained LMICs.
CONCLUSION
While acknowledging the profound impact of AI on laboratory medicine in LMICs, the study recognizes challenges such as inadequate data availability, digital infrastructure deficiencies, and ethical considerations. Successful implementation necessitates substantial investments in digital infrastructure, the establishment of data‐sharing networks, and the formulation of regulatory frameworks. The study concludes that collaborative efforts among stakeholders, including international organizations, governments, and nongovernmental entities, are crucial for overcoming obstacles and responsibly integrating AI into laboratory medicine in LMICs. A comprehensive, coordinated approach is essential for realizing AI's transformative potential and advancing health care in LMICs.
Journal Article > ReviewFull Text
JAC Antimicrob Resist. 17 May 2023; Volume 5 (Issue 3); dlad057.; DOI:10.1093/jacamr/dlad057
Lamrous A, Repetto EC, Depp T, Jimenez C, Chua AC, et al.
JAC Antimicrob Resist. 17 May 2023; Volume 5 (Issue 3); dlad057.; DOI:10.1093/jacamr/dlad057
OBJECTIVES
C-reactive protein (CRP) and procalcitonin (PCT) are widely used biomarkers in high-income countries. However, evidence for their use in low- and middle-income countries (LMICs) is scant. Because many factors, including rates of endemic disease, comorbidities and genetics, may influence biomarkers’ behaviour, we aimed to review available evidence generated in LMICs.
METHODS
We searched the PubMed database for relevant studies within the last 20 years that originated in regions of interest (Africa, Latin America, Middle East, South Asia or South East Asia), and full-text articles involving diagnosis, prognostication and evaluation of therapeutic response with CRP and/or PCT in adults (n = 88) were reviewed and categorized in 12 predefined focus areas.
RESULTS
Overall, results were highly heterogeneous, at times conflicting, and often lacking clinically useful cut-off values. However, most studies demonstrated higher levels of CRP/PCT in patients with bacterial versus other infections. HIV and TB patients had consistently higher levels of CRP/PCT versus controls. In addition, higher CRP/PCT levels at baseline and follow-up in HIV, TB, sepsis and respiratory tract infections were associated with poorer prognosis.
CONCLUSIONS
Evidence generated from LMIC cohorts suggests that CRP and PCT may have potential to become effective clinical guiding tools particularly in respiratory tract infections, sepsis and HIV/TB. However, more studies are needed to define potential scenarios for use and cost-effectiveness. Consensus across stakeholders regarding target conditions, laboratory standards and cut-off values would support the quality and applicability of future evidence.
C-reactive protein (CRP) and procalcitonin (PCT) are widely used biomarkers in high-income countries. However, evidence for their use in low- and middle-income countries (LMICs) is scant. Because many factors, including rates of endemic disease, comorbidities and genetics, may influence biomarkers’ behaviour, we aimed to review available evidence generated in LMICs.
METHODS
We searched the PubMed database for relevant studies within the last 20 years that originated in regions of interest (Africa, Latin America, Middle East, South Asia or South East Asia), and full-text articles involving diagnosis, prognostication and evaluation of therapeutic response with CRP and/or PCT in adults (n = 88) were reviewed and categorized in 12 predefined focus areas.
RESULTS
Overall, results were highly heterogeneous, at times conflicting, and often lacking clinically useful cut-off values. However, most studies demonstrated higher levels of CRP/PCT in patients with bacterial versus other infections. HIV and TB patients had consistently higher levels of CRP/PCT versus controls. In addition, higher CRP/PCT levels at baseline and follow-up in HIV, TB, sepsis and respiratory tract infections were associated with poorer prognosis.
CONCLUSIONS
Evidence generated from LMIC cohorts suggests that CRP and PCT may have potential to become effective clinical guiding tools particularly in respiratory tract infections, sepsis and HIV/TB. However, more studies are needed to define potential scenarios for use and cost-effectiveness. Consensus across stakeholders regarding target conditions, laboratory standards and cut-off values would support the quality and applicability of future evidence.
Conference Material > Abstract
Kaitano R
TB Research Dissemination Workshop, Epicentre Uganda. 29 June 2022
BACKGROUND
There is a growing interest for the use of stool samples as an alternative to respiratory samples for the diagnosis of intrathoracic TB in children unable to produce sputum. Unlike respiratory samples, stool samples require processing before molecular testing. Several groups have already evaluated different processing methods. However, it is difficult to know which method has the best diagnostic accuracy and potential for use at Primary Health Care level, due to the difference in study designs and populations.
METHODS
In this study, we performed a head to head comparison of the diagnostic accuracy and feasibility of four stool processing methods in the same population using the same study methodology. We selected three centrifuge-free simplified methods (Optimized Sucrose flotation (OSF), Stool Processing Kit (SPK) and Simple One Step (SOS)) and one centrifuge-based method (sucrose flotation) with well documented performance used as comparator. Two stool samples and two respiratory samples were collected from children with presumptive TB the Mbarara Regional Referral Hospital (Mbarara, Uganda), Lusaka University Teaching Hospital (Lusaka, Zambia) and the Arthur Davidson Children Hospital (Ndola, Zambia). Stool samples were split in four identical aliquots and processed with the different processing methods. Reference standard was the bacteriological results from respiratory specimens. Laboratory technicians’ perception of the methods was assessed using a self-administered questionnaire at different time points of the study.
RESULTS
Thirty-six children with Ultra or culture positive results from respiratory samples were enrolled to evaluate sensitivity and 140 children with two negative culture results to evaluate specificity of Ultra from stool using the different processing methods. Sensitivity of the different methods ranged between 56% and 69% and specificity was above 95% for all methods. The three centrifuge-free methods were perceived as easy to perform by the laboratory technicians.
CONCLUSION
Simplifying stool processing, regardless of the method used, did not decrease its performance when compared with the centrifuge-based method. All centrifuge free methods were feasible and well accepted by laboratory technicians.
These abstracts are not to be quoted for publication
There is a growing interest for the use of stool samples as an alternative to respiratory samples for the diagnosis of intrathoracic TB in children unable to produce sputum. Unlike respiratory samples, stool samples require processing before molecular testing. Several groups have already evaluated different processing methods. However, it is difficult to know which method has the best diagnostic accuracy and potential for use at Primary Health Care level, due to the difference in study designs and populations.
METHODS
In this study, we performed a head to head comparison of the diagnostic accuracy and feasibility of four stool processing methods in the same population using the same study methodology. We selected three centrifuge-free simplified methods (Optimized Sucrose flotation (OSF), Stool Processing Kit (SPK) and Simple One Step (SOS)) and one centrifuge-based method (sucrose flotation) with well documented performance used as comparator. Two stool samples and two respiratory samples were collected from children with presumptive TB the Mbarara Regional Referral Hospital (Mbarara, Uganda), Lusaka University Teaching Hospital (Lusaka, Zambia) and the Arthur Davidson Children Hospital (Ndola, Zambia). Stool samples were split in four identical aliquots and processed with the different processing methods. Reference standard was the bacteriological results from respiratory specimens. Laboratory technicians’ perception of the methods was assessed using a self-administered questionnaire at different time points of the study.
RESULTS
Thirty-six children with Ultra or culture positive results from respiratory samples were enrolled to evaluate sensitivity and 140 children with two negative culture results to evaluate specificity of Ultra from stool using the different processing methods. Sensitivity of the different methods ranged between 56% and 69% and specificity was above 95% for all methods. The three centrifuge-free methods were perceived as easy to perform by the laboratory technicians.
CONCLUSION
Simplifying stool processing, regardless of the method used, did not decrease its performance when compared with the centrifuge-based method. All centrifuge free methods were feasible and well accepted by laboratory technicians.
These abstracts are not to be quoted for publication
Conference Material > Video
Langendorf C
Epicentre Scientific Day Paris 2022. 21 June 2022
Conference Material > Video
Malaeb R, Nagwan Y
Epicentre Scientific Day Paris 2022. 21 June 2022
Conference Material > Abstract
Langendorf C
Epicentre Scientific Day Paris 2022. 1 June 2022
BACKGROUND
The Mini-Lab is a simplified and modular bacteriology laboratory being developed by MSF to improve access to microbiology diagnostics and antibiotic resistance surveillance in resource-limited settings. After a first pilot study in Haiti in 2020, this second evaluation aimed to assess the performance and ease-of use of the Mini-Lab integrated in the clinical routine of an MSF-supported hospital which has had no prior access to microbiology.
METHODS
The study was conducted after the implementation of the Mini-Lab in an MSFsupported hospital in Carnot, CAR, along with an antibiotic stewardship program. We included hospitalized patients with successful blood culture sampling on admission or during hospitalization, and who consented to study participation. The bacteria identified from blood culture in the Mini-Lab were shipped to a reference laboratory in Bicêtre hospital, France for identification (ID) and antibiotic susceptibility testing (AST) using reference methods. Laboratory technicians evaluated the usability of the Mini-Lab through repeated ease-of use questionnaires and competency assessment.
RESULTS
Between September 2021 and February 2022, we included 835 patients who had a total of 960 blood cultures. Positivity rate with pathogens was 12.5%. Over 121 pathogens identified in the Mini-Lab, 74 have been tested with reference methods so far and 68 (92.0%) gave ID results concordant with the Mini-Lab with 97.4% agreement to genus. No particular organism-antibiotic combination caused systematic errors on AST. Upon completion of the initial training, the laboratory technicians reported most of the aspects of the Mini-Lab easy to use, except for preparation and reading of ID and AST methods, which were reported to be simple after 3 months of experience. Assessment of the laboratory technicians' competencies after the initial training yielded very high scores (>90%) and 100% after 3 months.
CONCLUSION
The comparison of the Mini-Lab results with the reference methods for ID and AST showed overall very good results. We did not highlight any major malfunction preventing its deployment in other resource-limited countries.
KEY MESSAGE
The performances of the simplified and modular bacteriology laboratory, the Mini-Lab, are overall very good. We did not highlight any major malfunctions preventing its deployment in other fields.
This abstract is not to be quoted for publication
The Mini-Lab is a simplified and modular bacteriology laboratory being developed by MSF to improve access to microbiology diagnostics and antibiotic resistance surveillance in resource-limited settings. After a first pilot study in Haiti in 2020, this second evaluation aimed to assess the performance and ease-of use of the Mini-Lab integrated in the clinical routine of an MSF-supported hospital which has had no prior access to microbiology.
METHODS
The study was conducted after the implementation of the Mini-Lab in an MSFsupported hospital in Carnot, CAR, along with an antibiotic stewardship program. We included hospitalized patients with successful blood culture sampling on admission or during hospitalization, and who consented to study participation. The bacteria identified from blood culture in the Mini-Lab were shipped to a reference laboratory in Bicêtre hospital, France for identification (ID) and antibiotic susceptibility testing (AST) using reference methods. Laboratory technicians evaluated the usability of the Mini-Lab through repeated ease-of use questionnaires and competency assessment.
RESULTS
Between September 2021 and February 2022, we included 835 patients who had a total of 960 blood cultures. Positivity rate with pathogens was 12.5%. Over 121 pathogens identified in the Mini-Lab, 74 have been tested with reference methods so far and 68 (92.0%) gave ID results concordant with the Mini-Lab with 97.4% agreement to genus. No particular organism-antibiotic combination caused systematic errors on AST. Upon completion of the initial training, the laboratory technicians reported most of the aspects of the Mini-Lab easy to use, except for preparation and reading of ID and AST methods, which were reported to be simple after 3 months of experience. Assessment of the laboratory technicians' competencies after the initial training yielded very high scores (>90%) and 100% after 3 months.
CONCLUSION
The comparison of the Mini-Lab results with the reference methods for ID and AST showed overall very good results. We did not highlight any major malfunction preventing its deployment in other resource-limited countries.
KEY MESSAGE
The performances of the simplified and modular bacteriology laboratory, the Mini-Lab, are overall very good. We did not highlight any major malfunctions preventing its deployment in other fields.
This abstract is not to be quoted for publication
Protocol > Research Protocol
PLOS One. 25 April 2022; Volume 17 (Issue 4); e0267491.; DOI:10.1371/journal.pone.0267491
Ombelet S, Natale A, Ronat JB, Vandenberg O, Jacobs J, et al.
PLOS One. 25 April 2022; Volume 17 (Issue 4); e0267491.; DOI:10.1371/journal.pone.0267491
Use of equipment-free, “manual” blood cultures is still widespread in low-resource settings, as requirements for implementation of automated systems are often not met. Quality of manual blood culture bottles currently on the market, however, is usually unknown. An acceptable quality in terms of yield and speed of growth can be ensured by evaluating the bottles using simulated blood cultures. In these experiments, bottles from different systems are inoculated in parallel with blood and a known quantity of bacteria. Based on literature review and personal experiences, we propose a short and practical protocol for an efficient evaluation of manual blood culture bottles, aimed at research or reference laboratories in low-resource settings. Recommendations include: (1) practical equivalence of horse blood and human blood; (2) a diverse selection of 10 to 20 micro-organisms to be tested (both slow- and fast-growing reference organisms); (3) evaluation of both adult and pediatric bottle formulations and blood volumes; (4) a minimum sample size of 120 bottles per bottle type; (5) a formal assessment of usability. Different testing scenarios for increasing levels of reliability are provided, along with practical tools such as worksheets and surveys that can be used by laboratories wishing to evaluate manual blood culture bottles.
Journal Article > ResearchFull Text
Am J Trop Med Hyg. 18 April 2022; Volume Online version ahead of print; 1-5.; DOI:10.4269/ajtmh.21-1045
Chandna A, Richard-Greenblatt M, Tustin R, Lee SJ, Kain KC, et al.
Am J Trop Med Hyg. 18 April 2022; Volume Online version ahead of print; 1-5.; DOI:10.4269/ajtmh.21-1045
Host biomarker testing can be used as an adjunct to the clinical assessment of patients with infections and might be particularly impactful in resource-constrained settings. Research on the merits of this approach at peripheral levels of low- and middle-income country health systems is limited. In part, this is due to resource-intense requirements for sample collection, processing, and storage. We evaluated the stability of 16 endothelial and immune activation biomarkers implicated in the host response to infection stored in venous plasma and dried blood spot specimens at different temperatures for 6 months. We found that –80°C storage offered no clear advantage over –20°C for plasma aliquots, and most biomarkers studied could safely be stored as dried blood spots at refrigeration temperatures (4°C) for up to 3 months. These results identify more practical methods for host biomarker testing in resource-limited environments, which could help facilitate research in rural and remote environments.
Journal Article > ResearchFull Text
East Afr Med J. 31 March 2017; Volume 6 (Issue 2); 383.; DOI:10.4102/ajlm.v6i2.383
Orikiriza P, Nyehangane D, Atwine D, Kisakye JJ, Kassaza K, et al.
East Afr Med J. 31 March 2017; Volume 6 (Issue 2); 383.; DOI:10.4102/ajlm.v6i2.383
BACKGROUND
To confirm presence of Mycobacterium tuberculosis complex, some tuberculosis culture laboratories still rely on para-nitrobenzoic acid (PNB), a traditional technique that requires sub-culturing of clinical isolates and two to three weeks to give results. Rapid identification tests have improved turnaround times for mycobacterial culture results. Considering the challenges of the PNB method, we assessed the performance of the SD Bioline TB Ag MPT64 assay by using PNB as gold standard to detect M. tuberculosis complex from acid-fast bacilli (AFB) positive cultures.
OBJECTIVES
The aim of this study was to determine the sensitivity, specificity and turnaround time of the SD MPT64 assay for identification of M. tuberculosis complex, in a setting with high prevalence of tuberculosis and HIV.
METHODS
A convenience sample of 690 patients, with tuberculosis symptoms, was enrolled at Epicentre Mbarara Research Centre between April 2010 and June 2011. The samples were decontaminated using NALC-NaOH and re-suspended sediments inoculated in Mycobacterium Growth Indicator Tubes (MGIT) media, then incubated at 37 °C for a maximum of eight weeks. A random sample of 50 known negative cultures and 50 non-tuberculous mycobacteria isolates were tested for specificity, while sensitivity was based on AFB positivity. The time required from positive culture to reporting of results was also assessed with PNB used as the gold standard.
RESULTS
Of the 138 cultures that were AFB-positive, the sensitivity of the SD MPT64 assay was 100.0% [95% CI: 97.3 - 100] and specificity was 100.0% (95% CI, 96.4 - 100). The median time from a specimen receipt to confirmation of strain was 10 days [IQR: 8-12] with SD MPT64 and 24 days [IQR: 22-26] with PNB.
CONCLUSION
The SD MPT64 assay is comparable to PNB for identification of M. tuberculosis complex and reduces the time to detection.
To confirm presence of Mycobacterium tuberculosis complex, some tuberculosis culture laboratories still rely on para-nitrobenzoic acid (PNB), a traditional technique that requires sub-culturing of clinical isolates and two to three weeks to give results. Rapid identification tests have improved turnaround times for mycobacterial culture results. Considering the challenges of the PNB method, we assessed the performance of the SD Bioline TB Ag MPT64 assay by using PNB as gold standard to detect M. tuberculosis complex from acid-fast bacilli (AFB) positive cultures.
OBJECTIVES
The aim of this study was to determine the sensitivity, specificity and turnaround time of the SD MPT64 assay for identification of M. tuberculosis complex, in a setting with high prevalence of tuberculosis and HIV.
METHODS
A convenience sample of 690 patients, with tuberculosis symptoms, was enrolled at Epicentre Mbarara Research Centre between April 2010 and June 2011. The samples were decontaminated using NALC-NaOH and re-suspended sediments inoculated in Mycobacterium Growth Indicator Tubes (MGIT) media, then incubated at 37 °C for a maximum of eight weeks. A random sample of 50 known negative cultures and 50 non-tuberculous mycobacteria isolates were tested for specificity, while sensitivity was based on AFB positivity. The time required from positive culture to reporting of results was also assessed with PNB used as the gold standard.
RESULTS
Of the 138 cultures that were AFB-positive, the sensitivity of the SD MPT64 assay was 100.0% [95% CI: 97.3 - 100] and specificity was 100.0% (95% CI, 96.4 - 100). The median time from a specimen receipt to confirmation of strain was 10 days [IQR: 8-12] with SD MPT64 and 24 days [IQR: 22-26] with PNB.
CONCLUSION
The SD MPT64 assay is comparable to PNB for identification of M. tuberculosis complex and reduces the time to detection.