Journal Article > ReviewFull Text
Lancet Microbe. 12 August 2024; Online ahead of print; DOI:10.1016/S2666-5247(24)00134-4
Bertagnolio S, Dobreva Z, Centner CM, Olaru ID, Dona D, et al.
Lancet Microbe. 12 August 2024; Online ahead of print; DOI:10.1016/S2666-5247(24)00134-4
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ArXiv.org e-Print archive. 14 June 2024; DOI:10.48550/arXiv.2406.10044
Paulis LE, Schnerr RS, Halton J, Qin ZZ, Chua AC
ArXiv.org e-Print archive
E-Print archive
ArXiv.org e-Print archive. 14 June 2024; DOI:10.48550/arXiv.2406.10044
Ultraportable X-ray devices are ideal for TB screening in resource limited settings. Unfortunately, guidelines on the radiation safety of these devices are lacking. The aim of this study was to determine the radiation dose by scattered and leakage radiation of four ultraportable X-ray devices to provide a basis for these guidelines. Radiation dose measurements were performed with four ultraportable X-ray devices that meet the WHO/IAEA criteria. An anthropomorphic thorax phantom was positioned in posterioranterior orientation in a clinically representative X-ray set-up. X-ray exams were acquired with the following scan parameters: 90 kV, 2.5 mAs and maximum mAs, 1 m and 1.8 m sourceskin-distance. The entrance skin dose was measured at the center of the phantom. The scattered radiation dose was measured at 1 m from the phantom as a function of scatter angle. Leakage radiation was measured at 0.5 m from the X-ray tube with collimators closed and covered with additional lead. From the scatter measurements the ‘safe distance bunny’ was determined, which was the minimum distance to the phantom to stay below the international dose limit to the public (1 mSv/year) at a given workload: longest distance (related to highest scatter dose) was observed behind the edges of the detector and back towards the X-ray tube, whereas shortest distance (related to lowest scatter dose) was observed to the sides of the phantom. For the radiographer position, the total radiation dose by scattered and leakage radiation was determined in various scenarios. In most cases, the total radiation dose of ultraportable X-ray devices can be kept below 1 mSv/year by employing basic radiation safety rules: 1. reduce time in the X-ray field, 2. increase distance to the X-ray source, and 3. use shielding measures (e.g. lead apron). Ultraportable X-ray devices can be safely used for TB screening when using adequate precautions.
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.
Journal Article > ResearchFull Text
Emerg Infect Dis. 1 February 2016; Volume 22 (Issue 2); DOI:10.3201/eid2202.151238
Van der Bergh R, Chaillet P, Sow MS, Amand M, van Vyve C, et al.
Emerg Infect Dis. 1 February 2016; Volume 22 (Issue 2); DOI:10.3201/eid2202.151238
Rapid diagnostic methods are essential in control of Ebola outbreaks and lead to timely isolation of cases and improved epidemiologic surveillance. Diagnosis during Ebola outbreaks in West Africa has relied on PCR performed in laboratories outside this region. Because time between sampling and PCR results can be considerable, we assessed the feasibility and added value of using the Xpert Ebola Assay in an Ebola control program in Guinea. A total of 218 samples were collected during diagnosis, treatment, and convalescence of patients. Median time for obtaining results was reduced from 334 min to 165 min. Twenty-six samples were positive for Ebola virus. Xpert cycle thresholds were consistently lower, and 8 (31%) samples were negative by routine PCR. Several logistic and safety issues were identified. We suggest that implementation of the Xpert Ebola Assay under programmatic conditions is feasible and represents a major advance in diagnosis of Ebola virus disease without apparent loss of assay sensitivity.
Journal Blog > Perspective
Chua AC, Piriou E, Tran E, de Smet M, Henkens M
2 July 2020
Journal Article > ResearchFull Text
BMC Cardiovascular Disorders. 9 October 2021; Volume 21; 486.; DOI:10.1186/s12872-021-02298-7
Vetter B, Beran D, Boulle P, Chua AC, de la Tour R, et al.
BMC Cardiovascular Disorders. 9 October 2021; Volume 21; 486.; DOI:10.1186/s12872-021-02298-7
INTRODUCTION
Multi-parameter diagnostic devices can simplify cardiometabolic disease diagnosis. However, existing devices may not be suitable for use in low-resource settings, where the burden of non-communicable diseases is high. Here we describe the development of a target product profile (TPP) for a point-of-care multi-parameter device for detection of biomarkers for cardiovascular disease and metabolic disorders, including diabetes, in primary care settings in low- and middle-income countries (LMICs).
METHODS
A draft TPP developed by an expert group was reviewed through an online survey and semi-structured expert interviews to identify device characteristics requiring refinement. The draft TPP included 41 characteristics with minimal and optimal requirements; characteristics with an agreement level for either requirement of ≤ 85% in either the survey or among interviewees were further discussed by the expert group and amended as appropriate.
RESULT
Twenty people responded to the online survey and 18 experts participated in the interviews. Twenty-two characteristics had an agreement level of ≤ 85% in either the online survey or interviews. The final TPP defines the device as intended to be used for basic diagnosis and management of cardiometabolic disorders (lipids, glucose, HbA1c, and creatinine) as minimal requirement, and offering an expanded test menu for wider cardiometabolic disease management as optimal requirement. To be suitable, the device should be intended for level 1 healthcare settings or lower, used by minimally trained healthcare workers and allow testing using self-contained cartridges or strips without the need for additional reagents. Throughput should be one sample at a time in a single or multi-analyte cartridge, or optimally enable testing of several samples and analytes in parallel with random access.
CONCLUSIONS
This TPP will inform developers of cardiometabolic multi-parameter devices for LMIC settings, and will support decision makers in the evaluation of existing and future devices.
Multi-parameter diagnostic devices can simplify cardiometabolic disease diagnosis. However, existing devices may not be suitable for use in low-resource settings, where the burden of non-communicable diseases is high. Here we describe the development of a target product profile (TPP) for a point-of-care multi-parameter device for detection of biomarkers for cardiovascular disease and metabolic disorders, including diabetes, in primary care settings in low- and middle-income countries (LMICs).
METHODS
A draft TPP developed by an expert group was reviewed through an online survey and semi-structured expert interviews to identify device characteristics requiring refinement. The draft TPP included 41 characteristics with minimal and optimal requirements; characteristics with an agreement level for either requirement of ≤ 85% in either the survey or among interviewees were further discussed by the expert group and amended as appropriate.
RESULT
Twenty people responded to the online survey and 18 experts participated in the interviews. Twenty-two characteristics had an agreement level of ≤ 85% in either the online survey or interviews. The final TPP defines the device as intended to be used for basic diagnosis and management of cardiometabolic disorders (lipids, glucose, HbA1c, and creatinine) as minimal requirement, and offering an expanded test menu for wider cardiometabolic disease management as optimal requirement. To be suitable, the device should be intended for level 1 healthcare settings or lower, used by minimally trained healthcare workers and allow testing using self-contained cartridges or strips without the need for additional reagents. Throughput should be one sample at a time in a single or multi-analyte cartridge, or optimally enable testing of several samples and analytes in parallel with random access.
CONCLUSIONS
This TPP will inform developers of cardiometabolic multi-parameter devices for LMIC settings, and will support decision makers in the evaluation of existing and future devices.
Journal Article > ResearchFull Text
PLOS One. 25 August 2016; Volume 11 (Issue 8); DOI:10.1371/journal.pone.0161721
Dittrich S, Tadesse BT, Moussy FG, Chua AC, Zorzet A, et al.
PLOS One. 25 August 2016; Volume 11 (Issue 8); DOI:10.1371/journal.pone.0161721
Acute fever is one of the most common presenting symptoms globally. In order to reduce the empiric use of antimicrobial drugs and improve outcomes, it is essential to improve diagnostic capabilities. In the absence of microbiology facilities in low-income settings, an assay to distinguish bacterial from non-bacterial causes would be a critical first step. To ensure that patient and market needs are met, the requirements of such a test should be specified in a target product profile (TPP). To identify minimal/optimal characteristics for a bacterial vs. non-bacterial fever test, experts from academia and international organizations with expertise in infectious diseases, diagnostic test development, laboratory medicine, global health, and health economics were convened. Proposed TPPs were reviewed by this working group, and consensus characteristics were defined. The working group defined non-severely ill, non-malaria infected children as the target population for the desired assay. To provide access to the most patients, the test should be deployable to community health centers and informal health settings, and staff should require <2 days of training to perform the assay. Further, given that the aim is to reduce inappropriate antimicrobial use as well as to deliver appropriate treatment for patients with bacterial infections, the group agreed on minimal diagnostic performance requirements of >90% and >80% for sensitivity and specificity, respectively. Other key characteristics, to account for the challenging environment at which the test is targeted, included: i) time-to-result <10 min (but maximally <2 hrs); ii) storage conditions at 0-40°C, ≤90% non-condensing humidity with a minimal shelf life of 12 months; iii) operational conditions of 5-40°C, ≤90% non-condensing humidity; and iv) minimal sample collection needs (50-100μL, capillary blood). This expert approach to define assay requirements for a bacterial vs. non-bacterial assay should guide product development, and enable targeted and timely efforts by industry partners and academic institutions.
Journal Article > ResearchFull Text
PLOS One. 15 January 2020; Volume 15 (Issue 1); DOI:10.1371/journal.pone.0227773
Crumley I, Halton J, Greig J, Kahunga L, Mwanga JP, et al.
PLOS One. 15 January 2020; Volume 15 (Issue 1); DOI:10.1371/journal.pone.0227773
Introduction: High quality diagnostic imaging can provide increased diagnostic accuracy and help guide medical decision-making and management, however challenges for radiology in resource-limited settings are numerous. Diagnostic imaging and teleradiology have financial and logistical implications, so evidence of impact is crucial. We sought to test the hypothesis that the implementation of computed radiography with teleradiology consultation support will significantly change diagnoses and treatment plans in a resource limited setting.
Method: Paired before-after study to determine the therapeutic impact of an add-on diagnostic test. 'Preliminary Plan' and 'Final Plan' forms allowed direct comparison of diagnosis and treatment plans at initial consultation and following radiography and teleradiology. Consecutive consenting patients were included until the sample size (600) was reached. Changes in both diagnosis and treatment plan were analysed in the whole cohort, with sub-analyses of children aged <5 years, and cases of chest radiography.
Results: Final analysis included 536 cases. Diagnosis changed following radiography and teleradiology in 62% of cases, and treatment plans changed in 61%. In chest radiography cases, 70% of diagnoses and 62% of treatment plans changed, while in children <5 years 66% of diagnoses and 58% of treatment plans changed. Reduced final treatment plans were most common for exploratory surgery (72% decrease), surgical orthopaedic intervention (62% decrease), and TB treatment (52% decrease), allowing more conservative medical or surgical management in 61 cases. Increased final treatment plans were highest in the orthopaedic and interventional surgery and referral categories. Of 42 cases requiring interventional surgery in the final plan, 26 (62%) were identified only after radiography and teleradiology. 16 additional cases were indicated for orthopaedic surgery, 10 cases required patient transfer, and TB treatment was indicated in 45 cases. A change in the original prescription plan occurred in 41% of 536 cases, with one or more prescriptions stopped in 28% of all cases.
Conclusion: We found that computed radiography with teleradiology had significant clinical value in this resource-limited setting, with the potential to affect both patient outcomes and treatment costs through providing improved diagnostics and avoiding unnecessary treatments and medications.
Method: Paired before-after study to determine the therapeutic impact of an add-on diagnostic test. 'Preliminary Plan' and 'Final Plan' forms allowed direct comparison of diagnosis and treatment plans at initial consultation and following radiography and teleradiology. Consecutive consenting patients were included until the sample size (600) was reached. Changes in both diagnosis and treatment plan were analysed in the whole cohort, with sub-analyses of children aged <5 years, and cases of chest radiography.
Results: Final analysis included 536 cases. Diagnosis changed following radiography and teleradiology in 62% of cases, and treatment plans changed in 61%. In chest radiography cases, 70% of diagnoses and 62% of treatment plans changed, while in children <5 years 66% of diagnoses and 58% of treatment plans changed. Reduced final treatment plans were most common for exploratory surgery (72% decrease), surgical orthopaedic intervention (62% decrease), and TB treatment (52% decrease), allowing more conservative medical or surgical management in 61 cases. Increased final treatment plans were highest in the orthopaedic and interventional surgery and referral categories. Of 42 cases requiring interventional surgery in the final plan, 26 (62%) were identified only after radiography and teleradiology. 16 additional cases were indicated for orthopaedic surgery, 10 cases required patient transfer, and TB treatment was indicated in 45 cases. A change in the original prescription plan occurred in 41% of 536 cases, with one or more prescriptions stopped in 28% of all cases.
Conclusion: We found that computed radiography with teleradiology had significant clinical value in this resource-limited setting, with the potential to affect both patient outcomes and treatment costs through providing improved diagnostics and avoiding unnecessary treatments and medications.
Journal Article > ReviewFull Text
BMJ Glob Health. 7 February 2019; Volume 4 (Issue Suppl 2); e001112.; DOI:10.1136/bmjgh-2018-001112
Emperador DM, Mazzola LT, Trainor BW, Chua AC, Kelly-Cirino C
BMJ Glob Health. 7 February 2019; Volume 4 (Issue Suppl 2); e001112.; DOI:10.1136/bmjgh-2018-001112
Ebolaviruses and Marburg virus (MARV) both belong to the family Filoviridae and cause severe haemorrhagic fever in humans. Due to high mortality rates and potential for spread from rural to urban regions, they are listed on the WHO R&D blueprint of high-priority pathogens. Recent ebolavirus outbreaks in Western and Central Africa have highlighted the importance of diagnostic testing in epidemic preparedness for these pathogens and led to the rapid development of a number of commercially available benchtop and point-of-care nucleic acid amplification tests as well as serological assays and rapid diagnostic tests. Despite these advancements, challenges still remain. While products approved under emergency use licenses during outbreak periods may continue to be used post-outbreak, a lack of clarity and incentive surrounding the regulatory approval pathway during non-outbreak periods has deterred many manufacturers from seeking full approvals. Waning of funding and poor access to samples after the 2014–2016 outbreak also contributed to cessation of development once the outbreak was declared over. There is a need for tests with improved sensitivity and specificity, and assays that can use alternative sample types could reduce the need for invasive procedures and expensive equipment, making testing in field conditions more feasible. For MARV, availability of diagnostic tests is still limited, restricted to a single ELISA test and assay panels designed to differentiate between multiple pathogens. It may be helpful to extend the target product profile for ebolavirus diagnostics to include MARV, as the viruses have many overlapping characteristics.