Early Programmatic Implementation of Xpert MTB/RIF Testing
Early Programmatic Implementation of Xpert MTB/RIF Testing
The findings of this study begin to fill the gaps among guidelines, research findings, and real-world implementation of MTB/RIF testing, where NTPs and their partners work to test people with suspected TB and drug resistance. The projects documented here had a wide range of experiences, approaches and results, demonstrating the versatility of Xpert MTB/RIF, but also highlighting a number of barriers to implementation and possible solutions. As others have pointed out, the technology has great potential, but also has important limitations. This study begins to address some of the concerns delineated through implementation experiences in the field. These projects have showed that with proper support for procurement, infrastructure and supervision, Xpert MTB/RIF can be deployed at or very close to the point of care in many settings initially considered difficult because of the hurdles to overcome. Our findings generally coincide with other early assessments of the challenges and benefits of Xpert MTB/RIF implementation where many barriers can be surmounted if proper systems are in place and a coordinated country approach is taken with the best interests of the patient in mind.
Xpert MTB/RIF testing detected a large number of people with TB that routine services failed to detect. Data from South Africa shows similar results for MTB-positive yield but much lower error rates although many of the projects described here placed the machines in different types of facilities, including mobile units and primary care facilities in challenging settings. When available, the use of CXR as a highly sensitive screening tool should be considered before testing with Xpert MTB/RIF, to save cartridges and increase yield. Placing smear microscopy ahead of the MTB/RIF test in the diagnostic algorithm often resulted in lower yields compared with specimens tested directly on the MTB/RIF assay, as smear-positive patients were then excluded. However, the underlying prevalence of TB in the screened population, as well as the quality of smear microscopy services, play important roles in influencing yields among smear-negative specimens. Xpert MTB/RIF testing on smear-negative individuals, the general approach used here, expends significantly more resources and time, as all individuals are tested using smear microscopy and 80–90% of them are re-tested with Xpert MTB/RIF. New WHO guidance recommends that Xpert MTB/RIF replace smear microscopy when resources allow. All of the projects described here had external funding for Xpert MTB/RIF testing and so it is curious that only a few used it to replace smear, but this was many times limited by national policy.
Tracking the types, codes, reason, locations, and technicians associated with failed tests is important for users to improve performance. There are generally three possible types of failed tests for MTB/RIF: human, power supply and test-related. Human errors generally arose from inadequate sputum collection or specimen preparation and can be tracked by their numeric code. Automated reporting mechanisms can improve both the timeliness and accuracy of reporting errors and all results as well assist in supply chain management. Some projects had very high rates of Invalid results which seem to be caused by problems with the quality of the sputum sample and proper mouth cleansing techniques. Better coaching from staff may be able to help in these instances. While the failed test rates are much higher than in South Africa, they are similar to some other larger early implementer multi-country initiatives. Most of the projects placed the machines at lower level facilities which presents more of a challenge for implementation and supervision. An early experience in South Africa using mobile testing had comparable failed test results, although most were power supply related. [Personal Communication Liesl Page-Shipp] No result outcomes are often linked to power supply problems. In environments with irregular and unpredictable power, a backup power supply with an inverter should be capable of supporting the GeneXpert machine and computer for at least 2 hours in order to finish any test begun before a power failure (see Table 2). When GeneXpert machines are placed in facilities with other equipment needing power supply, generators are likely to be available and backup power may only be needed until the generator can be started. Ensuring timely calibration of the GeneXpert machines will also reduce errors. If the calibration is done after the module warranty expires and the module must be replaced, a new module or an extended warranty must be purchased. Modules can still fail outside of calibration and extended warrantees are available and should be purchased to protect the users.
As Xpert MTB/RIF provides both TB and rifampicin resistance results, it is important to weigh the benefit of early detection of drug resistance against the concern that large increases in DR-TB detection would overwhelm advanced diagnostic facilities and nascent drug-resistant TB treatment programs. Focusing MTB/RIF testing solely on DR-TB suspects is unlikely to produce large yields as the numbers of failures and retreatment cases at a district level is quite small in most settings. Furthermore, the majority of DR-TB cases will be found among new cases, requiring testing of people with suspected TB rather than patients already receiving TB treatment if meaningful MDR-TB treatment scale up is to take place. The application of algorithms focused on people with suspected TB will generally result in large increases in drug sensitive cases detected and a lower proportion of rifampicin resistant results. Nevertheless, DR-TB patients will be detected in greater numbers and with greater speed than under current conditions, and significant resources and coordination will be required for treatment, especially if MTB/RIF testing is to be done in areas without DR-TB treatment capacity as was the case in many of these projects. These projects were limited given funding was not provided for DR-TB treatment and active follow-up of rifimapicin resistant patients was generally not conducted and data is limited. However, in many countries, overall donor funding for DR-TB treatment remains unused as many people with DR-TB have not been diagnosed; so opportunities for expansion exist. Given the concern about slow expansion of MDR-TB treatment globally, South Africa has clearly shown that huge gains in detection and notification are possible in a short period of time using Xpert MTB/RIF as the primary diagnostic tool.
Apart from testing approaches and results, there were a number of other implementation issues that merit discussion. Although many point of care testing strategies focus on finger prick or dipstick testing, a recent review discussed the positioning of diagnostic tests in the health system and argued that many tests could be considered point of care, including smear microscopy and MTB/RIF, if the test and treat cycle could be completed in the same clinical encounter (or the same day). However, testing algorithms and work-flow practices often gets in the way of providing quick results to the patient and ensuring same-day TB treatment and this was seen in a number of projects. While Xpert MTB/RIF testing can provide highly sensitive results quickly in a number of different settings, the health system must provide a supportive environment; tightly controlling the machine and testing in high level laboratories may sometimes be achieved to the detriment of the patient. A recent study has made a strong argument for the use of MTB/RIF as a point-of-care test showing a reduction in delay, empiric treatment, and the ability of nurses to implement the test in primary care settings.
Decisions on machine location should be given careful consideration with respect to expected numbers of people tested and the need for referral systems in addition to power supply. Although many peripheral health facilities do not have the infrastructure to handle complicated testing, the main limitations we identified for decentralized MTB/RIF testing - algorithms, power, temperature and numbers of tests expected - can all be overcome with proper support, although in some remote areas supervision is difficult and seemed to complicate performance.
Training staff to use GeneXpert equipment was generally described as straightforward, supporting views of other early implementers. However, the need for retraining and supervision cannot be overlooked as staff turnover is a constant reality. As part of training, ensuring solidified national testing and treatment guidelines are in place is critical. Country adoption of the WHO policy guidance around testing algorithms as well as recent WHO new case and outcome definitions incorporating MTB/RIF and other WHO recommended tests, will greatly help standardize the process. All people with MTB/RIF positive results should be recorded as bacteriologically positive cases. The adoption of WHO recommended strategies and reporting systems will reduce the inconsistencies that the early implementers faced, though it must be acknowledged that field adoption of new guidance often takes time. Delays in customs clearing, in country transportation and other preparatory activities, such as training, will shorten the effective usage time for the cartridges. Staggering orders can help avoid expiry of cartridges, which have a short shelf life.
The technology has the possibility of being quite disruptive to national testing and treatment policy, and to recording and reporting forms and training. With donors including PEPFAR and The Global Fund beginning to fund the expansion of MTB/RIF testing in many countries, lessons learned from pilot projects that can be applied to a large expansion of testing must be disseminated. One of the main areas of concern about MTB/RIF testing is the additional cost to country diagnostic budgets which these projects did not have to address as the work was grant funded, therefore this experience cannot directly address or inform those concerns. Just as a few countries fund their own second line treatment programs, we feel that the benefits of improved diagnostics for TB and drug-resistant TB provide ample justification for long term support of improved diagnostics from donors. This study is not representative of all early implementer experiences with MTB/RIF testing but rather provides an overview of the shared issues across countries and of many different approaches to MTB/RIF implementation on a programmatic basis. Further programmatic studies are needed on issues such as case notification, time to diagnosis, cost effectiveness of MTB/RIF use in case finding programs and use at the most peripheral of health units (point of care testing) - all issues that our work was not designed to answer.
The experiences of these early implementers show that a variety of MTB/RIF testing approaches can be successfully employed across many different settings. This early information can be usefully applied in the on-going global scale up of MTB/RIF. The MTB/RIF test has limitations, but also provides an excellent opportunity to improve the way TB and drug-resistant TB are diagnosed on a wide scale.
Discussion and Conclusions
The findings of this study begin to fill the gaps among guidelines, research findings, and real-world implementation of MTB/RIF testing, where NTPs and their partners work to test people with suspected TB and drug resistance. The projects documented here had a wide range of experiences, approaches and results, demonstrating the versatility of Xpert MTB/RIF, but also highlighting a number of barriers to implementation and possible solutions. As others have pointed out, the technology has great potential, but also has important limitations. This study begins to address some of the concerns delineated through implementation experiences in the field. These projects have showed that with proper support for procurement, infrastructure and supervision, Xpert MTB/RIF can be deployed at or very close to the point of care in many settings initially considered difficult because of the hurdles to overcome. Our findings generally coincide with other early assessments of the challenges and benefits of Xpert MTB/RIF implementation where many barriers can be surmounted if proper systems are in place and a coordinated country approach is taken with the best interests of the patient in mind.
Xpert MTB/RIF testing detected a large number of people with TB that routine services failed to detect. Data from South Africa shows similar results for MTB-positive yield but much lower error rates although many of the projects described here placed the machines in different types of facilities, including mobile units and primary care facilities in challenging settings. When available, the use of CXR as a highly sensitive screening tool should be considered before testing with Xpert MTB/RIF, to save cartridges and increase yield. Placing smear microscopy ahead of the MTB/RIF test in the diagnostic algorithm often resulted in lower yields compared with specimens tested directly on the MTB/RIF assay, as smear-positive patients were then excluded. However, the underlying prevalence of TB in the screened population, as well as the quality of smear microscopy services, play important roles in influencing yields among smear-negative specimens. Xpert MTB/RIF testing on smear-negative individuals, the general approach used here, expends significantly more resources and time, as all individuals are tested using smear microscopy and 80–90% of them are re-tested with Xpert MTB/RIF. New WHO guidance recommends that Xpert MTB/RIF replace smear microscopy when resources allow. All of the projects described here had external funding for Xpert MTB/RIF testing and so it is curious that only a few used it to replace smear, but this was many times limited by national policy.
Tracking the types, codes, reason, locations, and technicians associated with failed tests is important for users to improve performance. There are generally three possible types of failed tests for MTB/RIF: human, power supply and test-related. Human errors generally arose from inadequate sputum collection or specimen preparation and can be tracked by their numeric code. Automated reporting mechanisms can improve both the timeliness and accuracy of reporting errors and all results as well assist in supply chain management. Some projects had very high rates of Invalid results which seem to be caused by problems with the quality of the sputum sample and proper mouth cleansing techniques. Better coaching from staff may be able to help in these instances. While the failed test rates are much higher than in South Africa, they are similar to some other larger early implementer multi-country initiatives. Most of the projects placed the machines at lower level facilities which presents more of a challenge for implementation and supervision. An early experience in South Africa using mobile testing had comparable failed test results, although most were power supply related. [Personal Communication Liesl Page-Shipp] No result outcomes are often linked to power supply problems. In environments with irregular and unpredictable power, a backup power supply with an inverter should be capable of supporting the GeneXpert machine and computer for at least 2 hours in order to finish any test begun before a power failure (see Table 2). When GeneXpert machines are placed in facilities with other equipment needing power supply, generators are likely to be available and backup power may only be needed until the generator can be started. Ensuring timely calibration of the GeneXpert machines will also reduce errors. If the calibration is done after the module warranty expires and the module must be replaced, a new module or an extended warranty must be purchased. Modules can still fail outside of calibration and extended warrantees are available and should be purchased to protect the users.
As Xpert MTB/RIF provides both TB and rifampicin resistance results, it is important to weigh the benefit of early detection of drug resistance against the concern that large increases in DR-TB detection would overwhelm advanced diagnostic facilities and nascent drug-resistant TB treatment programs. Focusing MTB/RIF testing solely on DR-TB suspects is unlikely to produce large yields as the numbers of failures and retreatment cases at a district level is quite small in most settings. Furthermore, the majority of DR-TB cases will be found among new cases, requiring testing of people with suspected TB rather than patients already receiving TB treatment if meaningful MDR-TB treatment scale up is to take place. The application of algorithms focused on people with suspected TB will generally result in large increases in drug sensitive cases detected and a lower proportion of rifampicin resistant results. Nevertheless, DR-TB patients will be detected in greater numbers and with greater speed than under current conditions, and significant resources and coordination will be required for treatment, especially if MTB/RIF testing is to be done in areas without DR-TB treatment capacity as was the case in many of these projects. These projects were limited given funding was not provided for DR-TB treatment and active follow-up of rifimapicin resistant patients was generally not conducted and data is limited. However, in many countries, overall donor funding for DR-TB treatment remains unused as many people with DR-TB have not been diagnosed; so opportunities for expansion exist. Given the concern about slow expansion of MDR-TB treatment globally, South Africa has clearly shown that huge gains in detection and notification are possible in a short period of time using Xpert MTB/RIF as the primary diagnostic tool.
Apart from testing approaches and results, there were a number of other implementation issues that merit discussion. Although many point of care testing strategies focus on finger prick or dipstick testing, a recent review discussed the positioning of diagnostic tests in the health system and argued that many tests could be considered point of care, including smear microscopy and MTB/RIF, if the test and treat cycle could be completed in the same clinical encounter (or the same day). However, testing algorithms and work-flow practices often gets in the way of providing quick results to the patient and ensuring same-day TB treatment and this was seen in a number of projects. While Xpert MTB/RIF testing can provide highly sensitive results quickly in a number of different settings, the health system must provide a supportive environment; tightly controlling the machine and testing in high level laboratories may sometimes be achieved to the detriment of the patient. A recent study has made a strong argument for the use of MTB/RIF as a point-of-care test showing a reduction in delay, empiric treatment, and the ability of nurses to implement the test in primary care settings.
Decisions on machine location should be given careful consideration with respect to expected numbers of people tested and the need for referral systems in addition to power supply. Although many peripheral health facilities do not have the infrastructure to handle complicated testing, the main limitations we identified for decentralized MTB/RIF testing - algorithms, power, temperature and numbers of tests expected - can all be overcome with proper support, although in some remote areas supervision is difficult and seemed to complicate performance.
Training staff to use GeneXpert equipment was generally described as straightforward, supporting views of other early implementers. However, the need for retraining and supervision cannot be overlooked as staff turnover is a constant reality. As part of training, ensuring solidified national testing and treatment guidelines are in place is critical. Country adoption of the WHO policy guidance around testing algorithms as well as recent WHO new case and outcome definitions incorporating MTB/RIF and other WHO recommended tests, will greatly help standardize the process. All people with MTB/RIF positive results should be recorded as bacteriologically positive cases. The adoption of WHO recommended strategies and reporting systems will reduce the inconsistencies that the early implementers faced, though it must be acknowledged that field adoption of new guidance often takes time. Delays in customs clearing, in country transportation and other preparatory activities, such as training, will shorten the effective usage time for the cartridges. Staggering orders can help avoid expiry of cartridges, which have a short shelf life.
The technology has the possibility of being quite disruptive to national testing and treatment policy, and to recording and reporting forms and training. With donors including PEPFAR and The Global Fund beginning to fund the expansion of MTB/RIF testing in many countries, lessons learned from pilot projects that can be applied to a large expansion of testing must be disseminated. One of the main areas of concern about MTB/RIF testing is the additional cost to country diagnostic budgets which these projects did not have to address as the work was grant funded, therefore this experience cannot directly address or inform those concerns. Just as a few countries fund their own second line treatment programs, we feel that the benefits of improved diagnostics for TB and drug-resistant TB provide ample justification for long term support of improved diagnostics from donors. This study is not representative of all early implementer experiences with MTB/RIF testing but rather provides an overview of the shared issues across countries and of many different approaches to MTB/RIF implementation on a programmatic basis. Further programmatic studies are needed on issues such as case notification, time to diagnosis, cost effectiveness of MTB/RIF use in case finding programs and use at the most peripheral of health units (point of care testing) - all issues that our work was not designed to answer.
The experiences of these early implementers show that a variety of MTB/RIF testing approaches can be successfully employed across many different settings. This early information can be usefully applied in the on-going global scale up of MTB/RIF. The MTB/RIF test has limitations, but also provides an excellent opportunity to improve the way TB and drug-resistant TB are diagnosed on a wide scale.
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