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not fit for purpose in endemic zones. These challenges define the direc-
tion of immediate work aimed at improving vivax malaria chemothera-
peutics, while also highlighting the need for research and development
of a new generation of therapies, especially hypnozoitocides that can be
used in G6PDd or pregnant patients.
Malariologists invented a lexicon in coping with the complexity of
the parasites and the diseases they cause. Figure 4.1 illustrates the classes of
antimalarial drugs divided according to targeted segment of the life cycle:
blood schizontocides kill asexual blood stages; tissue schizontocides kill active
asexual forms in the liver; hypnozoitocides kill dormant forms in the liver and
gametocytocides kill sexual forms in the blood. Sporontocides kill forms in the
mosquito, but no antimalarial drug is used clinically in this way. Drugs are
classified according to therapeutic intent, or the nature of activity against
the parasite at therapeutic doses.
Class identity has no specific bearing on chemical structure among
members of the class. Some drugs belong to several classes, but most
belong to just one. Class identity may change between species of plas-
modia; for example, primaquine is blood schizontocidal, gametocytocidal,
and hypnozoitocidal in vivax malaria, but is only gametocytocidal in fal-
ciparum malaria. Although blood schizontocidal for vivax malaria, prima-
quine is never administered with that therapeutic intent and few would
refer to it as a member of that class. Likewise, chloroquine is biologically
gametocytocidal in vivax malaria and not falciparum malaria, but the
therapeutic intent of chloroquine is never gametocytocidal and is thus
not thought of as such.
The aim in malaria chemotherapeutics is to achieve radical cure - elimi-
nation of all parasites from the body. What constitutes radical cure depends
on the infecting species and the chemotherapeutic targets it presents. No
recommended therapy aims to tackle all species and stages although such
an approach has pragmatic advantages for deployment ( Douglas et al.,
2011 ; Baird, 2012a ). For much of the endemic world, the radical cure of
P. vivax includes therapy directed at hypnozoites. Not all patients with
a diagnosis of vivax malaria have a relapse, hence the decision to pre-
scribe radical cure is presumptive, based on knowledge of the clinical
consequences of recurrent episodes, treatment efficacy and tolerability.
The term presumptive anti-relapse therapy (previously called 'terminal
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