Biology Reference
In-Depth Information
lower, potentially reducing the transmission potential to the mosquito vec-
tor (
Phyo et al., 2011
). The long-term benefits of prolonged post-exposure
prophylaxis are less clear. A single inoculation of
P. vivax
sporozoites can
seed the liver with multiple hypnozoites. Although slowly eliminated anti-
malarials will suppress the first, and possibly the second relapse in equatorial
regions, it remains to be shown whether this will reduce the total number
of relapses or simply delay the occurrence of the next one. These benefits
of PTP, unfortunately, reflect our limited ability to provide definitive cure
of the dormant liver stages of
P. vivax
. If hypnozoitocidal treatment can be
combined with ACTs in a reliable, safe, and effective way, then the superior
efficacy against
P. vivax
afforded by the longer-acting combinations would
be limited to a reduction in the rate of post-exposure reinfection that, in
most vivax endemic regions, is reasonably low.
6.2. Treatment of
P. vivax
Exoerythrocytic Stages
The ability of
P. vivax
to lie dormant in asymptomatic individuals presents
perhaps the greatest challenge for the clinical management of infection. This
difficulty impacts the success of control as well (
Douglas et al., 2010
;
Baird
and Hoffman, 2004
). Hypnozoites are insensitive to most blood schizonto-
cidal drugs, including those that show activity against liver-stage schizonts,
such as atovaquone + proguanil. The 8-aminoquinoline antimalarial drugs
exert hypnozoitocidal activity at nanomolar concentrations; only prima-
quine is licensed (
Galappaththy et al., 2007
), tafenoquine is in clinical devel-
opment and bulaquine has been abandonded (
Elmes et al., 2008
;
Krudsood
et al., 2006
). Apart from these agents, the pipeline for new hypnozoitocidal
candidates is remarkably dry (
Wells et al., 2010
).
The World Health Organization recommends a dose of 0.25-0.5 mg/kg
primaquine daily for 14 days for radical treatment of vivax malaria in those
who are not G6PDd (
World Health Organization, 2010
). However, the
evidence base from which these recommendations are derived is extremely
limited. The experimental and clinical evidence behind the total dose
effect has been detailed above and elsewhere (
Alving et al., 1960
;
Clyde
and McCarthy, 1977
). Trials have demonstrated that the standard low-dose
regimen of primaquine (total dose of 3.5 mg/kg) fails to prevent relapses in
many different endemic locations (
White, 2011
). For this reason, the most
recent WHO antimalarial guidelines recommended a high-dose regimen
of 7 mg/kg (equivalent to an adult dose of 30 mg per day for 14 days). In
practice, most endemic countries continue to recommend the lower total
dose out of fear of harm to unscreened G6PDd patients.
