Defining System Requirements for Simplified Blood Culture to Enable Widespread Use in Resource-Limited Settings
Abstract
:1. Introduction
2. Materials and Methods
2.1. Specialist Interviews
2.2. Target Product Profile Development Process
3. Results
3.1. Current Use of BCs in Low Resource Settings
3.2. Target Product Profile
3.2.1. Scope of the test
3.2.2. Test Performance
3.2.3. Test Procedure
3.2.4. Test Results
3.2.5. Consumables and Operational Characteristics
3.2.6. Cultural Considerations Beyond the TPP
4. Discussion
Supplementary Materials
Author Contributions
Acknowledgments
Conflicts of Interest
References
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City, County | Level [22] | Current System | Media Preparation | Delayed Entry | QC of Reagents | Reporting Protocol | Identification | AST |
---|---|---|---|---|---|---|---|---|
Vientiane, Lao PDR | 3–4 | Manual, daily check for turbidity; blood | Local | Sample transport from remote locations, try to receive within 24 hours of collection; transport at RT in a double-skinned insulated metal box | QC for agar made in-house | Gram stain, some rapid dx tests performed and the preliminary result is communicated verbally to clinicians ASAP and updated on a daily basis until there is a written a final report | API® (bioMerieux) | Disk diffusion |
Multiple, Cambodia | 3 | Manual, daily check for turbidity | Local | Ideally immediate; transport at RT | Central QC for media at manufacturer | Lab to call ward to inform doctor of result | Manual biochemical | Disk diffusion |
Gondar, Ethiopia | 3–4 | Manual, daily check for turbidity | Local | Ideally immediate, can be small delays; transport at RT | QC on media for sterility | Preliminary reports: growth (turbidity)—report Gram stain preliminary report, and finally drug susceptibility | Gram stain and then biochemical tests for Gram negative organism | Disk diffusion |
Gaborone, Botswana | 4 | Manual, daily check for turbidity | Procure | Ideally immediate, though delays up to 8 h; transport at RT | QC on media | Positive results reported in Laboratory Information Systems for some facilities; but manual reports are collected by hospital wards daily | Manual biochemical | Disk diffusion |
Multiple, Myanmar | 3–4 | Majority are manual | Local | Overnight delays > 12 h are common; transport at RT | No | Final report (~7 days) | Manual Biochemical (few level 4 centers are introducing Vitek2) | Disk diffusion (automated methods available for selected patients at very few Level 4 centers) |
Environmental Challenges | Implementation Challenges | |||||||||||
Country | Available at level | Power | Dust | Lab Temperature control | Humidity | Connectivity | Level of lab staff training | Quality Control for BC | Sample Collection (Volume, training) | Specimen Tracking | Result Reporting | |
Lao PDR | 3–4 | |||||||||||
Cambodia | 3 | |||||||||||
Ethiopia | 3–4 | |||||||||||
Botswana | 4 | |||||||||||
Guinea | 4 * | |||||||||||
Myanmar | 3 | |||||||||||
DR Congo | 3 | |||||||||||
Uganda | 3–4 |
Characteristic | Minimal | Optimal | Additional References |
---|---|---|---|
SCOPE | |||
Goal | A simplified blood culture system suitable for resource limited settings to support patient management and surveillance activities | ||
Target population | Total population (including neonates and immunocompromised individuals) presenting with fever | ||
Target level of health system | Level 3 (Regional/Provincial Hospital) and above | Appropriate for use in level 2 (District Hospital) | [22] |
Target user | Moderately trained lab technicians (e.g., 1–2 year certificates) | Lab technicians with limited training (e.g., 3–6 months, able to operate an integrated test with minimal additional steps) | [9] |
Platform cost | < US $20,000 | < US $5000 | |
Price of individual test (2 culture bottles) | < US $10 per test | < US $5 per test | |
TEST PERFORMANCE | |||
System detection capabilities | - Culture positivity, Gram status; - Antimicrobial susceptibility can be determined with additional methodologies | Pathogen identification and antimicrobial susceptibility are automated outputs of the system | |
Pathogen detection | > 95% sensitivity for detection of positive BC for either monomicrobial or polymicrobial | ||
Pathogen identification | Identifies 90% of isolates to species level, 95% genus level | Identifies 95% to species level, 99% to genus level | Standard BC and identification by MALDI-TOF MS is the reference [23,24]. |
Ability to determine the presence of mixed BCs | Not able to determine monomicrobial from polymicrobial infections | Able to determine monomicrobial from polymicrobial infections | |
Interfering substances | Able to provide an accurate result in the presence of malaria infection [25,26] | Able to provide an accurate result in the presence of malaria infection and/or antibiotics [27] | |
TEST PROCEDURE | |||
Ease of use/test complexity | The entire test procedure for system operation after sample collection to result should require a maximum of 2 steps by the user | The entire test procedure for system operation after sample collection to result should require a maximum of 1 step by the user and no additional steps required by user after the sample has been placed into the instrument | [19] |
Sample volume | - Test consumable (culture bottle) should support smaller volumes (5 mL or less) for pediatric samples and low volume draws; - Separate culture bottles for pediatric samples are acceptable | The same test consumable (culture bottle) should support smaller volumes (5 mL or less) for pediatric samples and low volume draws | International and local guidelines regarding blood volumes and number of samples collected should be followed |
Delayed entry | - Allows for room temperature storage of BC bottles post collection for <4 h prior to culture; - If sample transport takes longer than 2 h, incubation at 35 °C is preferred | [22] | |
QC testing of BC bottles | Same as standard BC | [28] | |
TEST RESULTS | |||
Preliminary result | Test reports positive or negative culture results | Test reports culture positive and > 95% Gram status and morphology information | |
Final result | Provides pathogen identification | Provides pathogens identification with resistance categories of interest (MRSA vs. MSSA, ESBL producing Enterobacteriaceae) and CRE | [29] |
Antimicrobial susceptibility testing | Antimicrobial susceptibility determination requires separate methodologies | Antimicrobial susceptibility is included as an automated output of the test result and therapy recommendations based on local treatment guidelines | |
Data interpretation and output | - Alert for preliminary and final report; - Capable of paper-based and electronic results to not only laboratory, but physician and ward of patient | Minimal requirements in addition to therapy recommendations based on local treatment guidelines | |
CONSUMABLES | |||
Sample collection components | None provided | All components required for sample collection are included in the kit | |
BC bottles | Only compatible with BC media bottles from the test manufacturer | Compatible with local manufacture of BC media bottles with a specified media formulation | |
Sample tracking/Patient identification | Compatible with 2D barcodes and labels | Stakeholder interviews | |
Storage conditions of BC bottles | 6 months at + 5 °C to 35 °C, 70% humidity, including transport stress (48 h at 50 °C); no cold chain required | 12 months at + 5 °C to + 40 °C at 90% humidity & transport stress (72 h at 50 °C); no cold chain required | High environmental temperatures and high humidity is often a problem in many countries. High environmental temperatures and high humidity is often a problem in many countries [30]. |
Shipping conditions of consumables & kit | No cold chain required; tolerance of transport stress for a minimum of 48 h at 5 °C to + 40 °C | No cold chain required; tolerance of transport stress for a minimum of 72 h at 5 °C to + 40 °C | Refrigerated transport is costly and often cannot be guaranteed during the entire transportation process. Frequent delays in transport are commonplace [30]. |
Waste disposal | Consumables should be able to be disposed of as biohazardous waste as specified by WHO guidelines according to the safe management of waste from health-care activities or per country regulations | [31] | |
OPERATIONAL CHARACTERISTICS | |||
Biosafety | Same as standard BC in a closed system; Biosafety alert is provided when a pathogen identified is on a predefined biosafety list | - No need for a biosafety cabinet; basic safety procedures need to be followed (standard PPE); - Alarms present for organisms that pose a biosafety risk for laboratory acquired infections | |
Operating conditions | - Between + 10 °C to + 35 °C at 70% humidity and at a max altitude of 2000 meters above mean sea level; - Ability to function in a high dust environment, with manual cleaning via standard lab consumable clean wipes or cleaning tool provided with the instrument | - Between + 5 °C to + 40 °C at 90% humidity and at a max altitude of 3000 meters above mean sea level; - Ability to function in a high dust environment with minimal manual cleaning required by user | High environmental temperatures and high humidity and dust are often an issue in LMICs. High environmental temperatures and high humidity and dust are often an issue in LMICs. |
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Dailey, P.J.; Osborn, J.; Ashley, E.A.; Baron, E.J.; Dance, D.A.B.; Fusco, D.; Fanello, C.; Manabe, Y.C.; Mokomane, M.; Newton, P.N.; et al. Defining System Requirements for Simplified Blood Culture to Enable Widespread Use in Resource-Limited Settings. Diagnostics 2019, 9, 10. https://doi.org/10.3390/diagnostics9010010
Dailey PJ, Osborn J, Ashley EA, Baron EJ, Dance DAB, Fusco D, Fanello C, Manabe YC, Mokomane M, Newton PN, et al. Defining System Requirements for Simplified Blood Culture to Enable Widespread Use in Resource-Limited Settings. Diagnostics. 2019; 9(1):10. https://doi.org/10.3390/diagnostics9010010
Chicago/Turabian StyleDailey, Peter J., Jennifer Osborn, Elizabeth A. Ashley, Ellen Jo Baron, David A. B. Dance, Daniela Fusco, Caterina Fanello, Yukari C. Manabe, Margaret Mokomane, Paul N. Newton, and et al. 2019. "Defining System Requirements for Simplified Blood Culture to Enable Widespread Use in Resource-Limited Settings" Diagnostics 9, no. 1: 10. https://doi.org/10.3390/diagnostics9010010