Biology Reference
In-Depth Information
infections,themajorityofwhichwillarisefromliver-stagerelapses.Therefore,judicious
massadministrationofhypnozoitocidaltherapywillreducetransmissionof P. vivax to
a greater extent than strategies focused on treatment of symptomatic patients. An
efficacious hypnozoitocidal agent with a short curative treatment course would be
particularlyusefulinmassdrugadministrationcampaigns.
1. INTRODUCTION
Plasmodium vivax threatens 2.85 billion people worldwide and infects
between 130 and 435 million people per year ( Guerra et al., 2010 ; Hay
et al., 2004 ; Price et al., 2007 ; Baird, 2007 ). By far, the greatest clinical
and numerical burden of disease is in Central and Southeast Asia . Plasmo-
dium vivax has unique characteristics that make it relatively refractory to
existing malaria control measures. The most important of these is its ability
to relapse from dormant liver forms (hypnozoites). As elimination efforts
'preferentially' reduce the burden of falciparum malaria, P. vivax is becom-
ing a proportionately more common cause of malaria ( Feachem et al., 2010 ;
Nosten et al., 2000 ; Rodriguez et al., 2011 ; Gama et al., 2011 ).
Anti-malarial drugs have an important role in reducing transmission
of malaria. However, drug discovery and development of novel agents has
focussed almost entirely on Plasmodium falciparum . Little priority has been
given to development of compounds especially for P. vivax . There are sev-
eral reasons for this. First, blood schizontocidal drugs that are active against
P. falciparum are also active against the blood stages of P. vivax. Second, our
inability to sustain P. vivax in continuous ex vivo culture significantly restricts
high-throughput in vitro drug-susceptibility testing ( Mueller et al., 2009 ).
Third, there is no standardised approach to assay anti-malarial activity against
hypnozoites . Plasmodium vivax has long been regarded as a benign infec-
tion and, therefore, has attracted less attention than its more virulent cousin
P. falciparum . However, recent studies have challenged this paradigm, high-
lighting P. vivax as a significant cause of morbidity and mortality (reviewed in
Chapter 3) and socioeconomic disruption. It is clear that the long-standing
neglect of this species is no longer tenable ( Price et al., 2007 ; Baird, 2007 ;
Tjitra et al., 2008 ; Genton et al., 2008 ; Beg et al., 2008 ; Barcus et al., 2007 ;
Lampah et al., 2011 ; Kochar et al., 2005 , 2009 ; Alexandre et al., 2010 ; Flower
et al., 2011 ; Tan et al., 2008 ; Bassat and Alonso, 2011 ; Anstey et al., 2009 ).
During the 1920s, P. vivax was used extensively for malariatherapy of
patients with neurosyphilis ( Austin et al., 1992 ). Many of these patients, as
well as 'volunteers' from penitentiaries, were enrolled in trials of early anti-
malarial compounds (see Chapter 4 for a comprehensive historical account
 
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