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Will Resistance to Antimalarial Drugs Halt Decades of Progress?

Symposium – Malaria Drug Resistance in Africa and Asia: Trends and Metrics

Sinwan Basharat (AMR Centre student liaison officer) – 25.04.2017


The event that informed this blog can be viewed online here.

Across the world, April 25 marks World Malaria Day. An annual day bringing international awareness to the major challenges and progress being made in curbing one of the deadliest diseases in human history. In a joint event organized by the London School of Hygiene & Tropical Medicine’s Malaria Centre and Antimicrobial Resistance Centre, this year’s theme examined the growing problem of resistance  to artemisinin combination therapy (ACT). The event featured six speakers and a panel discussion with experts on from molecular biology, parasitology, medical anthropology, surveillance data, clinical medicine, epidemiology, and international policy.

Cally Roper, Professor in Malaria Genetics at LSHTM, described how resistance is nothing new to the malaria field. In the late 1950s, chloroquine resistance emerged in South East Asia (around the border of Thailand and Cambodia) and spread across the world, followed by the emergence and spread of resistance to sulfadoxine/ pyrimethamine, mefloquine, and other drugs (though drug-resistance patterns have varied) (1).

The parallels between the past and the emergence of today’s artemisinin resistance are interesting, as ACT resistance was also first identified in South East Asia (2). ACTs are the recommended first line treatment globally, even in places where other drugs may still be effective. In the fight against malaria, along with wide distribution of long-lasting insecticide-treated nets (LLINS) and indoor residual spraying (IRS), ACTs have played an important role in preventing nearly 700 million cases of malaria between 2000-2015 (3). While the role of ACTs has been primarily to treat disease rather than reduce transmission, they have nonetheless played a key role in improving disease outcomes and preventing deaths.

However, the biggest question addressed, as put aptly by Colin Sutherland, Professor of Parasitology at LSHTM was, “Will ACT resistance spread beyond South East Asia, and what will happen in Africa?”. The greatest burden of malaria lies in Africa, which represents 90% of all cases worldwide. While the current ACT regimens are still highly effective in Africa there are some instances where treatments are taking longer to clear the parasite. If ACT resistance found in South East Asia reaches Africa, it could be catastrophic for the region and bring back decades of progress in malaria control.

Tackling this grave threat and answering this pressing question will require understanding the extent of the problem at hand. Georgina Humphries with the World-Wide Antimalarial Resistance Network (WWARN) at the University of Oxford, is coordinating this effort to assemble and analyze the data on antimalarial resistance. Aggregating published work from both clinical and lab based studies, her team is trying to piece together the fundamental questions of how resistance is emerging and the extent of its spread. She explained how their work examining the molecular markers of resistance will not just help to understand the parasite, but will play a key role in improving patient outcomes.

The event highlighted that beyond molecular and clinical epidemiology, tackling resistance will need to understand the social context of how ACT resistance is developing as well. Charlotte Gryseels, a medical anthropologist from the Institute of Tropical Medicine in Antwerp, described her work examining the social challenges faced by people in South East Asia and how curbing resistance will need to address those constraints. She explained how even though ACTs are available to people in the region, due to their high cost, patients often take just part of a dose and save some pills for later. In addition, due to a lack of testing in many clinics, patients often resort to widely available drug “cocktails” of antibiotics, ACTs, and fever reducing medicines. These inappropriate doses prevent complete clearance of the parasite and likely help to drive resistance. Some suggest that combatting resistance will require that patients take multiple courses of different ACTs (similar to the standard treatment of Tuberculosis). Gryseels explained that this would be extremely challenging given that adherence rates can be quite low even in the current two-drug regimens. This was echoed by David Reddy from Medicines for Malaria Venture who remarked, “We need to understand the social aspect of drug development to improve adherence. We simply cannot ignore the realities faced by patients living in poor communities.”

The complexity of ACT resistance clearly lies beyond just the evolution of the parasite and implementing solutions will need to consider the social and operational challenges. The event’s final speaker was Pascal Ringwald from the WHO’s Global Malaria Programme. He highlighted that there is great need to develop surveillance of ACT resistance beyond just South East Asia. Monitoring these emergence patterns can alert an appropriate response, and prevent the catastrophic effects of wide spread to Africa. Ringwald is also sceptical of recent findings that the first case of ACT resistance in Africa has occurred, and pressed colleagues to revaluate these findings (4). He concluded by stating that, fortunately, we have yet to reach doomsday, as in much of the world ACTs continue to be safe and effective treatments against malaria.

Overall, the event was very insightful and brought together a diverse set of attendees and speakers. “I was delighted by the breadth of topics covered and particularly enjoyed hearing that the WHO Global Malaria Programme is putting a strong emphasis on evidence-based policies”, remarked Ellie Sherrard, a post-doctoral fellow at Imperial College London.

With the growing problem of AMR, events like this aim facilitate collaboration and look at the issue beyond single areas of expertise. Gone are the days where a researcher would try to solve an issue isolated and removed from its surroundings. Today’s great discoveries and eureka moments are likely to occur when people from different perspectives share their views and ideas. Vanessa Racloz, an epidemiologist from Novartis, was very pleased with the event saying, “I enjoyed that today’s event focused not only on the technical and molecular challenges in anti-malarial resistance, but also discussed the important social hurdles. Working in pharmaceutical industry myself, I know its not always about just finding the right drug. The event was just brilliant, the diversity in speakers was fascinating”.

The full event can be viewed online via Panopto.

 

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Panel discussion at the World Malaria Day symposium at London School of Hygiene & Tropical Medicine on 25 April 2017. (L-R) Marta Tufet (for Royal Society of Tropical Medicine & Hygiene), Colin Sutherland (LSHTM), Pascal Ringwald (Global Malaria Program, WHO), David Reddy (Medicines for Malaria Venture), Georgina Humphreys (World-Wide Antimalarial Network [WWARN]), Shunmay Yeung (LSHTM), and Charlotte Gryseels (Institute of Tropical Medicine). Not shown: Cally Roper (LSHTM). Photo courtesy of IDDO/Anne Whitehouse.

 


 

References

  1. A. O. Talisuna, P. Bloland, U. D’Alessandro, Clin.Microbiol.Rev. 17, 235–254 (2004).
  2. A. M. Dondorp et al., N. Engl. J. Med. 361, 455–467 (2009).
  3. S. Bhatt et al., Nature. 526, 207–11 (2015).
  4. F. Lu et al., N. Engl. J. Med. 376, 991–993 (2017).
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