Biology Reference
In-Depth Information
have begun to be committed, and scientists and clinicians may now unleash
those and their collective intellect upon this remarkably complex problem.
Fielding safe and effective radical cure represents the greatest urgency
across a very broad front of necessary work. In the short and expedient term,
a course justified by both the stakes and the prospects for success, existing
therapies must be optimized for safety and efficacy in patients, especially
among the G6PDd, pregnant and small children. As given in Section
3
, this
is by no means a trivial task. It requires the kind of focus, determination and
commitment exhibited by Alving, his colleagues and sponsors, but without
a global war spurring progress. It also requires grasp of very complex issues
underpinning rational and efficient experimental and clinical approaches.
Above all, the community of malariology should accept the heavy burden
of bringing therapies to bear against the problem of vivax malaria as it
occurs in endemic zones; that is, where specific diagnosis of infection and
screening against dangerous contraindications is very often absent.
9.1. Proof of Efficacy
The loss of chloroquine-primaquine for radical cure, real or looming,
demands proof of efficacy for new partners to primaquine (and tafenoquine)
in this essential chemotherapeutic tool. The apparent reliance of primaquine
upon its co-drug for efficacy raises the possibility that not all new blood
schizontocides will be suitable partner drugs in radical cure. These new ther-
apies against the acute attack must be evaluated with primaquine and its effi-
cacy and safety against relapse. The recent trial in Indonesian soldiers already
described (
Sutanto, in preparation
) provides hopeful evidence that other
drugs do indeed permit good primaquine efficacy against relapse despite
60 years of continuous and widespread improper use. The effective co-drug
in that instance, from dihydroartemisinin-piperaquine treatment, was almost
certainly the very long-lived piperaquine component. Primaquine was not
administered to those subjects until day 28, the approximate elimination
half-life of piperaquine. This single trial firmly points to dihydroartemisinin-
piperaquine combined with primaquine as a highly efficacious radical cure,
and in so doing addresses the most conspicuous gap in vivax malaria chemo-
therapeutics. These promising results should embolden further such efforts.
9.2. Proof of Safety
Standard primaquine dosing (210-420 mg over 14 days, or shorter) will
not be proven safe in unscreened G6PDd patients. That is an issue for strat-
egies aimed at minimizing harm, like less threatening dosing or G6PDd
