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Wells T.N.C.,Medicines for Malaria Venture | Burrows J.N.,Medicines for Malaria Venture | Baird J.K.,Eijkman Oxford Clinical Research Unit | Baird J.K.,University of Oxford
Trends in Parasitology | Year: 2010

Plasmodium vivax is the major species of malaria parasite outside Africa. It is especially problematic in that the infection can relapse in the absence of mosquitoes by activation of dormant hypnozoites in the liver. Medicines that target the erythrocytic stages of Plasmodium falciparum are also active against P. vivax, except where these have been compromised by resistance. However, the only clinical therapy against relapse of vivax malaria is the 8-aminoquinoline, primaquine. This molecule has the drawback of causing haemolysis in genetically sensitive patients and requires 14 days of treatment. New, safer and more-easily administered drugs are urgently needed, and this is a crucial gap in the broader malaria-elimination agenda. New developments in cell biology are starting to open ways to the next generation of drugs against hypnozoites. This search is urgent, given the time needed to develop a new medication. © 2010 Elsevier Ltd. All rights reserved. Source


Kevin Baird J.,Eijkman Oxford Clinical Research Unit | Kevin Baird J.,University of Oxford
Clinical Microbiology Reviews | Year: 2013

Vivax malaria threatens patients despite relatively low-grade parasitemias in peripheral blood. The tenet of death as a rare outcome, derived from antiquated and flawed clinical classifications, disregarded key clinical evidence, including (i) high rates of mortality in neurosyphilis patients treated with vivax malaria; (ii) significant mortality from zones of endemicity; and (iii) the physiological threat inherent in repeated, very severe paroxysms in any patient, healthy or otherwise. The very well-documented course of this infection, with the exception of parasitemia, carries all of the attributes of "perniciousness" historically linked to falciparum malaria, including severe disease and fatal outcomes. A systematic analysis of the parasite biomass in severely ill patients that includes blood, marrow, and spleen may ultimately explain this historic misunderstanding. Regardless of how this parasite is pernicious, recent data demonstrate that the infection comes with a significant burden of morbidity and associated mortality. The extraordinary burden of malaria is not heavily weighted upon any single continent by a single species of parasite-it is a complex problem for the entire endemic world, and both species are of fundamental. © 2013, American Society for Microbiology. All Rights Reserved. Source


Baird J.K.,Eijkman Oxford Clinical Research Unit | Baird J.K.,University of Oxford
International Journal for Parasitology | Year: 2012

Treatment of acutely ill patients, informed by a diagnosis of the species of Plasmodium involved, has long dominated strategic thinking in malaria chemotherapeutics. This bias for both acute illness and access to diagnosis resulted in therapeutic strategies poorly suited to malaria as it occurs in endemic zones. Most of those malarias do not provoke illness and occur beyond diagnostic reach for technical or practical reasons. Therapies effective against all species and stages would likely prove more practical in endemic zones, especially if safely administered without laboratory screening for contraindications. The primary impediment to such therapies is the mild to severe hemolytic toxicity of primaquine in patients with glucose-6-phosphate dehydrogenase deficiency. Primaquine is the only treatment licensed for therapy against relapse caused by dormant liver stages occurring in some species, and against the sexual blood stages responsible for transmission to mosquitoes in all species. Despite being licensed over 50. years ago, no alternative drugs have been developed, and safer dosing regimens of primaquine have not been explored. These failures forestalled the emergence of therapies practical for use in endemic zones, especially in the context of eliminating transmission. © 2012 Australian Society for Parasitology Inc. Source


Baird J.K.,Eijkman Oxford Clinical Research Unit | Baird J.K.,University of Oxford
Current Infectious Disease Reports | Year: 2012

Most malaria diagnosed outside endemic zones occurs in patients experiencing the consequences of what was likely a single infectious bite by an anopheline mosquito. A single species of parasite is nearly always involved and expert opinion on malaria chemotherapy uniformly prescribes species- and stage-specific treatments. However the vast majority of people experiencing malaria, those resident in endemic zones, do so repeatedly and very often with the involvement of two or more species and stages of parasite. Silent forms of these infections-asymptomatic and beyond the reach of diagnostics-may accumulate to form substantial and unchallenged reservoirs of infection. In such settings treating only the species and stage of malaria revealed by diagnosis and not others may not be sensible or appropriate. Developing therapeutic strategies that address all species and stages independently of diagnostic evidence may substantially improve the effectiveness of the control and elimination of endemic malaria. © The Author(s) 2012. Source


Baird J.K.,Eijkman Oxford Clinical Research Unit | Baird J.K.,University of Oxford
Pathogens and Global Health | Year: 2013

The maxim 'an ounce of prevention is worth a pound of cure' finds few better demonstrations than with malaria caused by Plasmodium vivax. Thoroughly neglected over the past 60 years, the chemotherapy of this complex infection has been dangerous and ineffective until the present. Work is at last being done, but seeing that translate to real improvements at the periphery of care delivery will take years of deliberate effort. In the meantime, patients face substantial risk of debilitating, threatening, and fatal courses of illness associated with a diagnosis of vivax malaria. For some of the most vulnerable to such outcomes - pregnant women and infants - repeated attacks of acute vivax malaria from a single infectious anopheline bite is now not preventable. One of the few measures than can be immediately applied with rigor is vector control, thereby effectively preventing as many of these difficult and dangerous infections as possible. This commentary emphasizes the dire consequences of infection by P. vivax and the real difficulty of dealing with them. That, in turn, emphasizes the many benefits to be derived by preventing them in the first place. © W. S. Maney & Son Ltd 2013. Source

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