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Column: Vivax malaria, breaking the cycle of endless suffering - by George Jagoe

July 10, 2014 - 10:56 -- Ingeborg van Schayk
"And I saw Sisyphus at his endless task raising his prodigious stone with both his hands. With hands and feet he tried to roll it up to the top of the hill, but just before he could roll it over the other side, its weight would be too much for him, and the pitiless stone would come thundering down again on to the plain. Then he would begin trying to push it up hill again, and the sweat ran off him and the steam rose after him."
The Odyssey of Homer, translated by Samuel Butler
In the summer of 1982, I went to Belize with a group of teenage volunteers, living in a village not far from Belmopan, the capital.  Our host, Ricardo, was a charismatic 30-year-old community organizer, trained in agronomy and responsible for a local chapter of the 4-H organization, a U.S. based international youth development organization.  He was bright, articulate, and an inspiring role model for us adolescents.  One week into our field work, he made a passing comment, casually muttering "Next week, I’ll probably be out of commission for a few days."
“What do you mean, you’ll be ‘out of commission’?”
“About once every 4-6 weeks, I come down with a bout of malaria.  It’s pretty miserable.  Like having the flu.”
I had been well-briefed about malaria before we arrived in Central America, and was dutifully taking weekly chloroquine tablets for prophylaxis.  But I had never encountered anyone with malaria. I probed – and he obliged by describing his affliction in detail.  I learned of his misery due to the recurrent high fevers, of writhing and lying in puddles of sweat for 2-4 days at a time.  I was aghast at the idea of this bright community leader laid low every month. 
“And you can’t treat it?” I asked.
“Well, I take some kind of sulfa drugs.  When the fever comes, they can help me get better faster… But it always comes back.”

Malaria wears many masks.  For some newcomers, the first image they encounter is that of an African child in a perilous struggle with acute falciparum.  My first close-up view was of a chronic vivax patient – a full-grown, productive community leader, rendered helpless by monthly combat with an enemy that wouldn’t let go… but that toyed with him, giving him a few weeks to recover before the next round of punishment.   Like Sisyphus, lugging a huge stone uphill only to have it roll back down, Ricardo was locked in an exhausting struggle with relapsing vivax.  I was fascinated by the disease and horrified by the suffering it engendered.  And I wished there were something that could give battered fighters like Ricardo a better chance against this wicked adversary.

Vivax has often been called the neglected member of the malaria family.  Perhaps its lower death rates compared to falciparum led the malaria community to give it less attention as the world struggled to beat back the resurgence of falciparum that followed from the failed elimination efforts of the 1960s.  And as a result, vivax flourished.  In the early 2000s, researchers led by WHO estimated the global health burden of vivax malaria alone at 70-80 million cases annually. [1]  In 2009, Mueller et al. estimated the burden between 80 and 300 million cases annually, with up to 2.5 billion people at risk. [2] 
Today, researchers are revisiting the historical view that vivax is a more benign form of malaria.  While it is true that acute vivax infections are generally less life-threatening than those from falciparum, there is growing evidence of the debilitating impact on patients worn down by years of relapsing malaria.   The deadly face of vivax reveals itself in a litany of declining health indicators: “… a spectrum of severe disease that essentially resembles that of falciparum malaria: cerebral malaria (including generalised seizure and status epilepticus), hepatic dysfunction with severe jaundice, acute lung injury, acute respiratory distress syndrome, pulmonary oedema, shock, renal failure, splenic rupture, severe thrombocytopenia and haemorrhage, and severe anaemia.” [2]
To cure an acute bout of vivax, chloroquine (CQ) is effective in clearing blood stage infections in most settings, while ACTs are required where emerging resistance has undermined CQ’s effectiveness.   But to undo the Sisyphean curse – to kill off the sleeping parasite reservoirs that hide out in the human liver, unresponsive to blood-stage cures – the drug tool kit is decidedly weaker.  For over 60 years, primaquine administered over 14 consecutive days has been the recommended cure for liver stage infections.  Sadly, surveys and studies have shown that primaquine ranks high as one of the antimalarials with the worst compliance – most patients simply will not complete such a lengthy course of treatment.
I am part of a drug development partnership that works with industry and research partners to speed up the development and delivery of new malaria medicines.  This year, we and our partners are guardedly excited about a single dose cure that may do in one day what primaquine does in fourteen.  Large drug trials beginning now will help us determine this medicine’s safety and efficacy; it will take a few years until we know for sure.   Farther back in the pipeline, some drug candidates may offer even better ways to stamp out vivax completely from the human body– but it’s too soon to say.
Despite the unknowns, the pharmacopeia of the future looks much brighter than it did in 1982 when I listened to Ricardo recount his stories of relapsing malaria with a weary sense of resignation.    In the universe of Greek legends, Sisyphus will spend the rest of eternity purging his offenses by pushing the same rock up the same hill every day.  But here on our earthly plain – we are making exciting progress to break the cycle of endless suffering of Ricardo and other vivax patients.
[1] ”The Neglected Burden of Plasmodium Vivax Malaria.” Kamini Mendis, Barbara J. Sina, Paola Marchesini, and Richard Carter
Am. J. Trop. Med. Hyg., 64(1, 2)S, 2001, pp. 97–106

[2] ”Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite.”   Ivo Mueller PhD,Mary R Galinski PhD,J Kevin Baird PhD,
Jane M Carlton PhD,Dhanpat K Kochar MD,Pedro L Alonso MD,Hernando A del Portillo PhD
The Lancet Infectious Diseases - 1 September 2009 ( Vol. 9, Issue 9, Pages 555-566 )
DOI: 10.1016/S1473-3099(09)70177-X

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).