Malaria Treatment & Prevention

Please welcome our expert panelists.

—Paul Stannard
Deputy Director of Procurement, USAID/Deliver Project

--Lawrence M. Barat, MD, MPH
Dr. Lawrence Barat serves as Senior Malaria Advisor at the US Agency for International Development (USAID), working on the President’s Malaria Initiative. Dr. Barat received his medical degree from SUNY Downstate Medical Center and an MPH from the Harvard School of Public Health. He completed a residency in Internal Medicine at SUNY Downstate and a fellowship in Infectious Diseases at Boston University School of Medicine (BUSM). In 1992, he joined the BUSM faculty and worked with the Boston City Hospital Clinical AIDS Program and the Harvard Hospitals/Boston City Hospital AIDS Clinical Trials Unit. From 1992 to 1993, Dr. Barat also served as AIDS Policy Advisor for the Mayor of Boston and played an instrumental role in starting the first legal needle exchange program in Massachusetts. Dr. Barat joined the Malaria Branch at the Centers for Disease Control and Prevention (CDC), where his research focused on malaria diagnosis and treatment, including groundbreaking work on the quality and utilization of diagnostic testing for malaria. In 2000, Dr. Barat was seconded to the World Bank by CDC, where he led the Bank ...

Please welcome our expert panelists.

—Paul Stannard
Deputy Director of Procurement, USAID/Deliver Project

--Lawrence M. Barat, MD, MPH
Dr. Lawrence Barat serves as Senior Malaria Advisor at the US Agency for International Development (USAID), working on the President’s Malaria Initiative. Dr. Barat received his medical degree from SUNY Downstate Medical Center and an MPH from the Harvard School of Public Health. He completed a residency in Internal Medicine at SUNY Downstate and a fellowship in Infectious Diseases at Boston University School of Medicine (BUSM). In 1992, he joined the BUSM faculty and worked with the Boston City Hospital Clinical AIDS Program and the Harvard Hospitals/Boston City Hospital AIDS Clinical Trials Unit. From 1992 to 1993, Dr. Barat also served as AIDS Policy Advisor for the Mayor of Boston and played an instrumental role in starting the first legal needle exchange program in Massachusetts. Dr. Barat joined the Malaria Branch at the Centers for Disease Control and Prevention (CDC), where his research focused on malaria diagnosis and treatment, including groundbreaking work on the quality and utilization of diagnostic testing for malaria. In 2000, Dr. Barat was seconded to the World Bank by CDC, where he led the Bank’s Malaria Team, sat on the Roll Back Malaria Global Partnership Board, and helped design and implement successful malaria control programs in India and Eritrea. He left the Bank in 2004 to work for AED, where he supported several USAID projects, including NetMark, BASICS, SARA and Africa 2010. Dr. Barat joined USAID’s PMI Team in May 2007, where he has provided technical leadership on malaria case management, has overseen implementation activities several countries, and coordinates a US-Brasil collaboration on malaria control. During his 13 years career in malaria control, Dr. Barat has worked in more than 20 countries on three continents and has published widely on areas as diverse as the quality and use of diagnostic testing for malaria and the distribution of malaria burden and interventions by wealth status. He is acknowledged as one of the world’s experts on malaria diagnosis, having led initiatives to develop comprehensive guidance to countries on scaling up diagnostic testing for malaria and chairing the Diagnosis Workstream of RBM’s Case Management Working Group.

--Megan Moynahan
Megan brings insight into the unique culture and workings of FDA’s Center for Devices and Radiological Health, having 15 years experience at FDA including six years as the branch chief for the premarket branch responsible for new pacemakers and defibrillators. Well-networked across all functional units within the Center, Megan uses her influence at multiple levels of the organization to shape Center thinking and bring about change. Her successful cross-functional working group became the model for a Center-wide reorganization in 2008. In 2009, she was the chief architect for the Center’s Signal Escalation program, a Center-wide business process focused on product safety that she cultivated as an in-house “start-up”. Megan joined the Office of the Center Director in 2008 as the Network Leader for Cardiac Electrophysiology and Monitoring Devices, and is now a core member of the Innovation Team. Her background is in biomedical engineering with emphasis on electrical engineering and control systems. Her current areas of focus on the innovation team include wireless telemetry, continuous physiological monitoring, biosensors, and robotics.

Dear All, I would like to address the question about cost effectiveness and integration into existing systems. Whereas the RDT is considered by most as a purely diagnostic tool to decide wheteher to treat or not, there is another aspect. To the epidemiologist a positive test means and incident case. These data can be collected weekly as we are doing in Zambia, tranferred to a central analyst by SMS (the nurses at health centres do this and get reimbursed for talk time) and the Ministry of Health has information about outbreaks ocurring. Te plan is to develop infrastrcuture to use these data for targeting interventions. In the long run, we are developing a system that can change malarai control strategies, so one should consider this when you consider the value of the test. I hope one of the USAID people will comment. They know about this work in Zambia, and it will be good to know tht the RDT becomes a respected tool in the anti malaria armory for several reasons. I speak on behalf of the Malaria Institute at Macha as well as the Johns Hopins Malaria Institute. Clive Shiff

I'd like to provide FDA's comment to the first question, but first I'd like to introduce the subject matter expert who provided the information to me: Freddie M. Poole, MS, is the Associate Director of the Division of Microbiology Devices in the Office of In Vitro Diagnostic Devices, and supervises review and approval of Bacteriology, Mycobacteriology, Mycology, Parasitology, and AST Devices. She received her MS from Georgetown University and Virginia Polytechnical University, and her undergraduate degree from Catholic University in P.R., and her Medical Technology Training from Catholic Medical Centers of Brooklyn & Queens, School of Medical Technology. She started her FDA career in 1985 as a Scientific Reviewer in the Microbiology Branch where she reviewed marketing applications for infectious disease diagnostics, published guidance documents, and worked with various work groups s. She is currently the FDA/CDRH representative on the Interagency Antimicrobial Resistance Steering Committee and The Federal TB Task Force. Freddie is also involved with CLSI and currently serves as a member of the Area Committee for Microbiology and the FDA/CDRH Advisor to the Antimicrobial and Antifungal Subcommittees, and is an active member of the American Society for Microbiology. She also serve from 2004 ...

I'd like to provide FDA's comment to the first question, but first I'd like to introduce the subject matter expert who provided the information to me: Freddie M. Poole, MS, is the Associate Director of the Division of Microbiology Devices in the Office of In Vitro Diagnostic Devices, and supervises review and approval of Bacteriology, Mycobacteriology, Mycology, Parasitology, and AST Devices. She received her MS from Georgetown University and Virginia Polytechnical University, and her undergraduate degree from Catholic University in P.R., and her Medical Technology Training from Catholic Medical Centers of Brooklyn & Queens, School of Medical Technology. She started her FDA career in 1985 as a Scientific Reviewer in the Microbiology Branch where she reviewed marketing applications for infectious disease diagnostics, published guidance documents, and worked with various work groups s. She is currently the FDA/CDRH representative on the Interagency Antimicrobial Resistance Steering Committee and The Federal TB Task Force. Freddie is also involved with CLSI and currently serves as a member of the Area Committee for Microbiology and the FDA/CDRH Advisor to the Antimicrobial and Antifungal Subcommittees, and is an active member of the American Society for Microbiology. She also serve from 2004 to present on the WHO, Tropical Disease Research Programme “Diagnostic Evaluation Expert Panel”.

Here's Dr Poole's reply to the first question: In order for a malaria RDT to be distributed in the U.S. premarket clearance is required. Malaria RDTs have been classified under 21CFR 866.3402 as "Plasmodium species antigen detection assays", Class II devices. A description of these devices can be found in our Code of Federal Regulations, which is also available on our website at:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm

Information on submitting a premarket notification for Malaria RDTs can be found on our website in our guidance "Class II Special Controls Guidance Document: Plasmodium Species Antigen Detection Assays" at:
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocumen...

A sample FDA review of a cleared assay for Plasmodium species can be found at:
http://www.accessdata.fda.gov/cdrh_docs/reviews/K061542.pdf

Additional information on marketing a device in the US can be found on our website at:
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYour...

Here is Dr Poole's response to the second question, What are challenges to successful implementation?
FDA Response: Some challenges to successful implementation are:
1) inadequate laboratory training of users
2) tests developed in US were not evaluated under conditions present in developing countries.
e.g., extreme temperatures, power outages, contamination in laboratory facilities
3) cost of RDTs

WHO has published guidelines for diagnostic evaluations for Malaria and other RDTS in Nature Reviews - Microbiology. The Malaria review was published in September, 2006. They are available at no cost on their website at:

http://www.nature.com/nrmicro/journal/v8/n12_supp/full/nrmicro1522.htm
http://www.nature.com/nrmicro/journal/v4/n9_supp/full/nrmicro1524.html

Dr. Moynahan, with the help of Dr. Poole, have provided an comprehensive answer to how RDTs are registered in the United States. Outside of the US, and particularly in countries with malaria transmission, the processes are often not clear or not defined. Many countries do not register medical devices. Those that do have disparate processes. Even in countries with registration requirements, RDTs are often deployed in the private and public sector without ever getting clearance for the appropriate regulatory body.

Recognizing the limitations of regulatory authorities in many countries, WHO, the Foundation for Innovative New Diagnostics (FIND), and CDC have developed a scheme for testing the quality of Rapid Diagnostic Tests in a standardized fashion against whole blood samples of known parasite density. Three rounds of testing have been carried out from 2009 to 2011, although results for the third round are not yet available. Results from the first round can be found at: http://www.who.int/malaria/publications/atoz/9789241599467/en/index.html. Not suprisingly, some RDTs performed very well and other rather poorly.

Using these results, WHO consulted technical experts on malaria diagnosis and representatives from funding agencies to develop criteria for selecting high-quality RDTs that are ...

Dr. Moynahan, with the help of Dr. Poole, have provided an comprehensive answer to how RDTs are registered in the United States. Outside of the US, and particularly in countries with malaria transmission, the processes are often not clear or not defined. Many countries do not register medical devices. Those that do have disparate processes. Even in countries with registration requirements, RDTs are often deployed in the private and public sector without ever getting clearance for the appropriate regulatory body.

Recognizing the limitations of regulatory authorities in many countries, WHO, the Foundation for Innovative New Diagnostics (FIND), and CDC have developed a scheme for testing the quality of Rapid Diagnostic Tests in a standardized fashion against whole blood samples of known parasite density. Three rounds of testing have been carried out from 2009 to 2011, although results for the third round are not yet available. Results from the first round can be found at: http://www.who.int/malaria/publications/atoz/9789241599467/en/index.html. Not suprisingly, some RDTs performed very well and other rather poorly.

Using these results, WHO consulted technical experts on malaria diagnosis and representatives from funding agencies to develop criteria for selecting high-quality RDTs that are intended to guide countries in selecting the test kit that is appropriate for their specific country context and is of the highest quality (http://www.who.int/malaria/diagnosis_treatment/diagnosis/en/index.html). Many countries have used these criteria when selecting an RDT for public sector use. In addition, a consortium of agencies that procure large quantities of RDTs (WHO, UNICEF, World Bank, USAID/PMI, the Global Fund, and MSF) who procure approximately 80% of all RDTs manufactured globally, have agreed to adhere to the criteria set out in the WHO guidance. Finally, WHO also has adopted the WHO/FIND/CDC scheme as the basis for their new pre-qualification scheme for RDTs.

The challenges for implementation are, in many ways, no different from the challenges of implementing any new disease control strategy in developing countries. For implementation of RDTs, the greatest challenges include having sufficient resources to procure sufficient quantities of RDTs to meet country needs, having a supply chain that ensures that RDTs are available at every point of care whenever they are needed, and ensuring the quality of the tests and of the people using the tests.

In most malaria-affected countries, lack of resources for RDTs is not a major barrier. With support from the Global Fund, the US President's Malaria Initiative, the World Bank, UNICEF, and WHO, most malaria-affected countries have sufficient funding to procure the necessary quantities of RDTs. When one also takes into account that RDTs, particularly in low to moderate prevalence settings, should result in significantly reduced consumption of malaria treatment, at least some of the cost of RDTs will be offset by reduced requirements for ACTs.

In contrast, one of the greatest barriers to implementation in most countries is weak supply chain systems. Even in countries that have successfully scaled-up the use of RDTs at national scale, such as Senegal and Ethiopia, stock outs ...

The challenges for implementation are, in many ways, no different from the challenges of implementing any new disease control strategy in developing countries. For implementation of RDTs, the greatest challenges include having sufficient resources to procure sufficient quantities of RDTs to meet country needs, having a supply chain that ensures that RDTs are available at every point of care whenever they are needed, and ensuring the quality of the tests and of the people using the tests.

In most malaria-affected countries, lack of resources for RDTs is not a major barrier. With support from the Global Fund, the US President's Malaria Initiative, the World Bank, UNICEF, and WHO, most malaria-affected countries have sufficient funding to procure the necessary quantities of RDTs. When one also takes into account that RDTs, particularly in low to moderate prevalence settings, should result in significantly reduced consumption of malaria treatment, at least some of the cost of RDTs will be offset by reduced requirements for ACTs.

In contrast, one of the greatest barriers to implementation in most countries is weak supply chain systems. Even in countries that have successfully scaled-up the use of RDTs at national scale, such as Senegal and Ethiopia, stock outs of RDTs at front-line health facilities and at community level are far too common. Despite years of investment by PMI, PEPFAR, and other donors, the drug and commodity management systems in many countries remain very weak. In some countries, donors have moved to parallel systems to deliver malaria commodities, including RDTs, but these are only stop-gap measures. Without improved supply chain management systems, there is a great risk that RDT implementation will ultimately fail in some countries.

Lastly, although RDTs are relatively easy to use, compared to malaria microscopy, ensuring quality is dependent on several factors, including procuring a high-quality product, quality testing to screen out poor quality lots, maintaining a "cool chain" from the factory to the point of care, good training of RDT users, periodic supervision to monitor adherence to test procedures and appropriate interpretation of results. In addition, it is essential to train clinicians on appropriate use of the tests and in how the results should guide treatment, which should be reinforced through periodic supervision.

The two replies from Lawrence Barat sum up the issues very well, in terms of the major challenges for RDT supply. It is not so much the product itself but the supply chain that is weak.
As Lawrence has mentioned the work by WHO/FIND has provided some exellent guidance in the selection criteria for RDTs and their information note of September 2010 is a resource worthy of note.
For the USAID Deliver Project quality of product is essential and for all procurement of RDTs we undertake lot testing through WHO/FIND at Institut Pasteur in Cambodia and the Research Institute for Tropical Medicine in the Philippines. RDTs are not released for shipment until the test results are completed. In addition both labs retain samples for interval testing to monitor real-time temperature stability.

Today marks the last day of the Malaria RDT Panel. We covered many aspects of RDTs from the test, to training, to procurement. We hope you found this panel useful. In the next few weeks, we will post a discussion brief that outlines this panel. While the official panel has ended, please feel free to continue the discussion and post new questions or comments as they arise.

Finally, I'd like to say thank you to our expert panelists for their excellent comments and for sharing their experiences.

Today marks the last day of the Malaria RDT Panel. We covered many aspects of RDTs from the test, to training, to procurement. We hope you found this panel useful. In the next few weeks, we will post a discussion brief that outlines this panel. While the official panel has ended, please feel free to continue the discussion and post new questions or comments as they arise.

Finally, I'd like to say thank you to our expert panelists for their excellent comments and for sharing their experiences.

you are welcome Ailis and hope we shall continue to discuss on these very important questions surrounding malaria treatment and control