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Column: Mass Drug Administration – A Kaleidoscope of New Opportunities?

May 5, 2014 - 20:19 -- Bart G.J. Knols

Mass Drug Administration (MDA) is a tantalizing tool that can support elimination efforts and help dramatically knock down malaria prevalence.  Why isn’t it more widely used?

by George Jagoe

The use of medicines on a mass scale to wipe out parasite reservoirs and improve individual patient health status is enormously appealing.   The annals of public health victories show how judicious mass-drug-administration (MDA) has rolled back the burden of horrific parasitic diseases (e.g. river blindness, lymphatic filariasis, trachoma).    At its best, MDA marries the optimal use of effective drugs with well-coordinated delivery to improve disease outcomes radically...

Past successes also show that MDA’s effectiveness is linked to other accompanying interventions, including health education and community mobilization.  To diminish the logistical burden of MDA and insure its sustainability, it should be integrated with existing healthcare delivery systems to the greatest degree possible.
In the case of malaria, MDA’s track record has been patchy.  The WHO Standard Treatment Guidelines (second revision, 2010) only dedicates ~500 words to the topic – and draws a cautious conclusion based on the published evidence over a 60-year period: in an extensive analysis of 19 MDA projects, only one contributed to a sustained drop in transmission.  And that one instance occurred with a small population (<1.000 people) on an isolated island in the Pacific Ocean, with the benefit of a decade-long follow-up period of close surveillance and response.
Yet the tantalizing allure of MDA remains.  Few dispute that a large-scale MDA campaign can show very satisfactory short-term results, with dramatic drops in malaria prevalence, improved health indicators, and diminished transmission.  In the aftermath of an MDA campaign, for a brief moment, one catches an exhilarating glimpse of a happier healthier future --- the way life should be… near zero transmission, near zero disease burden, no malaria deaths.  Unfortunately, MDA work that is not part of a well-designed elimination effort is like a sand castle built near the high tide line: no matter how beautiful the short-term result, waves of malaria without fail will come crashing back, destroying the good work.  This setback, sadly, has been seen time and again.
Malaria MDA is once again in the spotlight, thanks to new energy from funders and implementers, and promising breakthroughs in the necessary toolkit.  A more promising mix of drugs today can be strategically deployed to support MDA.  There are new opportunities for integrated approaches that combine MDA with improved prevention tools.  And lastly, MDA is increasingly considered with more nuance – instead of seeing it as a panacea, malaria programmes and researchers are more tactical, deploying it in select settings at the right moment in the long-term battle to defeat malaria, alongside other needed interventions.
From the perspective of new drug development, these are some of the key considerations relating to MDA:
(1) Drugs with good killing efficacy and long half-lives.  Compared to 15 years ago, the rise of ACTs as the preferred treatment for curing malaria has led to five different combination therapies in this family of drugs.  Within the ACT cluster, those combinations that help prevent reinfection for the longest period of time after administration are being considered for potential use in MDA (e.g. DHA-PQP.)
(2) Drugs with strong safety profiles.  MDA means giving drugs to whole populations – healthy (uninfected) individuals, as well as patients, both symptomatic and asymptomatic.  As a result, calculating the risk-benefit of giving drugs to this wide human target is different from treating patients who are in immediate danger from a deadly disease.  MDA drugs ideally should be well tolerated and easily administered.
(3) Drugs that will not undermine today’s best treatment drugs.  One of WHO’s long-standing concerns with MDA has been the risk that highly effective drugs used to cure malaria could be undermined by the widespread use of similar drugs in MDA.  Therefore, MDA strategies should include resistance surveillance and give due consideration to ensuring that effective treatment options are preserved.
(4) Judicious use of drugs in targeted populations at the “right” moment.  Although the gold standard for many implementers would be to use MDA across whole populations in programmed campaigns, there are other strategies that target sub-segments of a population for limited MDA.  In this latter case, the focus may be to provide patient protection versus targeting overall reduction of parasite biomass in the community.   The promising role of Seasonal Malaria Chemoprevention in W. Africa is one example of using targeted MDA potentially to yield massive health benefits for children under the age of five.
We are on the verge of game-changing transitions.  Malaria prevalence has been dropping in the majority of malaria endemic countries.  More countries are developing sub-national /regional strategies based on local prevalence conditions.  In some of those settings, MDA may be appropriately used.  The drug toolkit is better than it has been for decades and new, easier-to-use medicines in development should lessen the logistical burden of MDA. Lastly, national capacity to manage the challenges of MDA is improving in many countries, from stronger central management of malaria control programmes down to expanded cadres of community healthcare workers. 
Seasoned malaria experts who lived through the euphoria of promising elimination campaigns 50-60 years ago may click their tongues and urge caution for those who today are rallying around the promise of MDA-style campaigns.  Out of respect for those who watched the crash-and-burn of poorly conceived MDA efforts, we should acknowledge the risks that MDA may face in future elimination efforts.  At the same time, we need to reassure those experienced veterans that this time, the ambitions will be bolstered by better science, focused deployment, and improved technology.  And most importantly, there should be a humble acknowledgement that the long-term surveillance-and-response that follows MDA is just as important as the quality of the drug campaign itself – and both merit equal attention.

George Jagoe 
George heads up the Access & Product Management team at Medicines for Malaria Venture (MMV), a non-profit drug development partnership based in Geneva, Switzerland.  He and his team focus on those malaria drugs developed by MMV and its partners that are in the final stages of development and/or post-launch use. The goal: to ensure that these tools can gain acceptance and overcome access barriers in order to have maximum impact in saving patients' lives.

Prior to joining MMV, George has had a variety of roles in healthcare consulting, health systems management, and pharma-related endeavors. He was the first Country Director for the Clinton Foundation’s HIV/AIDS Initiative in Mozambique, where working with national and international stakeholders, CHAI helped introduce antiretroviral treatments into the national health system. After that experience, he led the sales and marketing division of Specialty Care products (Oncology, Neuroscience, and Infection) for AstraZeneca Spain. With family roots in Spain (Catalunya) and the USA (Washington, DC; Boston), George isn’t sure what to say when people ask him where he’s from, but he has a very warm spot in his heart for Barcelona. He holds a marketing and healthcare MBA from the Kellogg School of Management (USA) and an undergraduate degree from Harvard College (USA).