Rapid malaria diagnosis: where we stand and where we need to go
Preparing RDTs for quality testing in one of three WHO-FIND lot testing laboratories
Question & Answer with Dr. David Bell, Head of Malaria Diagnostics Programme at FIND (formerly Scientist/Malaria Diagnostics at WHO/WPRO)
Q: What would you say is the main impact of the WHO/FIND/CDC report on the performance of certain malaria rapid diagnostic tests (RDTs) and why was there a need to do this study?
A: There is a very large range of malaria RDTs on the market but little comparative data on their performance. This has resulted in major uncertainty for programs in trying to make good procurement decisions. The report demonstrates that there are very good RDTs available but that there is a wide variation in RDT quality. The results will enable programs to make rational procurement decisions based on the evidence of RDT performance and they also set a clearer standard to guide manufacturers in optimizing their products.
Q: How should programs use the product testing results?
A: The results provide a useful snapshot of RDT quality. The product evaluation program tested two lots of each product. We know that variation in product quality can occur due to poor manufacture or exposure to high temperatures during transport and storage, so while the results of this report provide an important guide for procuring the best tests, it is still necessary to check the new lots of each product before use. We also expect that several manufacturers will be able to improve the quality of their products now that a clear standard of performance has been set.
The testing program assesses various aspects of RDT performance. The importance of certain factors, such as heat stability and ease of use, will vary according to the area where RDTs are used and the level of training of the technicians. Along with the performance data from this evaluation, other important aspects of diagnostics program management, such as the need for retraining and product cost, will also need to be taken into account in decision making. As with procurement of anti-malarial drugs, procurement of malaria diagnostics is a complex process and must be tied to well planned and structured program implementation.
Training in use of RDTs by health workers, Zambia
Q: Could you elaborate how programs would go about checking the performance of new batches of RDTs?
A: WHO and FIND coordinate lot testing in three regional laboratories (Philippines, Cambodia, Ethiopia) and this service is available free of charge. Programs send RDTs to these laboratories and results are normally returned within five working days. A large number of national programs and implementing agencies are already accessing this service. It is also recommended that some monitoring occur at a field level against high-quality microscopy. The WHO/FIND program is working with various partners to develop new techniques for village level monitoring.
Q: Where should national control programs be using RDTs?
A: WHO recommends that parasite-based diagnosis be the basis for malaria case management in all but exceptional situations. This makes good sense, as the majority of fevers are not due to malaria, even in most areas of sub-Saharan Africa. It is important to distinguish which fevers are due to malaria in order to avoid wasting anti-malarial drugs, to reduce pressure towards resistance to these drugs and to improve the early management of other causes of fever. In many areas, microscopy is impractical and RDTs are therefore the only way to achieve this.
Q: Do you believe we have all the diagnostic tools needed for the control and elimination of malaria, or would you agree that we still need better tools?
A: The product testing results demonstrate that there are RDTs currently available that are adequate for malaria case management in most areas. However, it’s important to have tests that maintain this high level of performance and that remain stable during long term storage in all malaria endemic areas. The challenge for manufacturers is to maintain this high performance when producing the tests in very large quantities to address the huge potential requirement for diagnosis of malaria-like febrile illness, particularly for detection of non-falciparum malaria. It may prove that this can best be addressed through the development of new types of tests. There is also a growing interest in the detection of low parasite density infections in asymptomatic patients being screened in malaria elimination programs. It is likely that new point of care tests detecting DNA or other markers will be necessary to achieve this on a large scale. More information is also needed on the effectiveness of current tests for detecting malaria in special situations such as pregnancy, and for monitoring the effectiveness of anti-malarial drugs.
Q: Is FIND planning to develop more stable or sensitive tests for malaria? Please elaborate.
A: FIND is working with a number of partners to determine the suitability of more stable antibodies that have potential for use in malaria rapid tests. We hope this work will benefit test manufacturers and malaria programs in the future. FIND is also engaged with partners in developing point of care DNA detection tests which have great potential for screening populations and detecting low density parasite infections at a much more sustainable cost, making large-scale population surveys a possibility for elimination programs, blood bank screening, and diagnostic programs with similar requirements.
Q: What do you think should be done towards establishing a sustainable quality control system for the massive scale-up of RDTs?
A: Massive scale-up of RDTs will be necessary if we are to allow all febrile patients in malaria-endemic areas to have access to good case management, that is, to receive anti-malarial drugs when they need them and good management of non-malarial fever when that is required.
The WHO/FIND malaria RDT evaluation program, backed in part by the Bill & Melinda Gates Foundation, supports both product testing and a number of laboratories to lot test RDTs, ensuring that good quality RDTs can be procured and that their quality is checked before they are released to the field. We consider that such a program is essential to ensure that populations in endemic areas can have confidence in these tests when they are used to determine treatment for this potentially fatal illness. It is also important that monitoring of quality continue in the field. At present, this is limited to comparison with microscopy, but the WHO/FIND program is developing new methods (positive control wells) which should greatly improve the ability of every health worker using RDTs to have confidence that the tests they are using are working correctly.
Establishing a comprehensive quality control system for RDTs is an essential requirement for malaria control programs, as it is for diagnostic programs for any other disease. This requires careful planning, rigorous implementation and adequate funding. It is important that not only malaria programs, but also the major funding agencies that support them, recognize this and ensure that the introduction of malaria RDTs goes well beyond procurement, but addresses all aspects necessary for a successful program - from policy development to training, community education and strengthening of the health systems necessary for the management of other causes of febrile illness.
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