Biology Reference
In-Depth Information
(AS + SP) and dihydroartemisinin plus piperaquine (DHA + PIP).
Plasmodium vivax
resistance to the artemisinins has not been described but
cross-resistance of chloroquine-resistant
P. vivax
strains to amodiaquine
results in high rates of recurrent infections following AS + AQ in regions
such as Eastern Indonesia and Papua New Guinea (
Hasugian et al., 2007
;
Karunajeewa et al., 2008
). Although SP has low inherent efficacy against
P. vivax
(
Darlow et al., 1982
), AS + SP is efficacious in the absence of SP
resistance (
Tjitra et al., 2002
); however, this combination is not recom-
mended for
P. vivax
due to the widespread presence of antifolate resis-
tance in this species (
Karunajeewa et al., 2008
;
Tjitra et al., 2002
;
Imwong
et al., 2003
). Although the initial therapeutic response of
P. vivax
follow-
ing treatment with AM + LUM, AS + MQ or DHA + PIP is generally
excellent, the rates of
P. vivax
recurrence within 42 days vary considerably.
This reflects the variability in the duration of post-treatment prophylaxis
against recurrent infection provided by the partner drug.
3.2. Post-treatment Prophylaxis
Slowly eliminated blood schizontocidal drugs that remain above minimum
inhibitory concentrations for a long time after administration have the
potential to reduce markedly recurrent
P. vivax
parasitaemia following acute
infection (
Douglas et al., 2010
,
2011
;
Ratcliff et al., 2007
;
Karunajeewa et al.,
2008
). On the island of New Guinea, where relapses tend to occur every
3 weeks, the slowly eliminated combination dihydroartemisinin + pipera-
quine (half-life of piperaquine ∼28 days (
Hung et al., 2004
;
Tarning et al.,
2008
)) is associated with a two- to fourfold lower risk of recurrence than
artemether + lumefantrine (half-life of lumefantrine ∼3.2 days (
Ezzet et al.,
2000
)) within 42 days of treatment (
Ratcliff et al., 2007
;
Karunajeewa et al.,
2008
). Where relapses occur less frequently, the period of post-treatment
prophylaxis is less likely to cover the first relapse and, therefore, the benefit
of a long period of time above minimum inhibitory concentration will be
limited to a brief period of refractoriness to reinfection.
Increasing anti-malarial drug resistance permits parasites to grow in
greater concentrations of drug. In low-grade resistance, concentrations of
drug may be sufficient to eradicate most of the initial parasite biomass,
but the period of time for which the drug is above minimum inhibitory
concentration decreases. The first manifestation of such resistance is a
reduction in the duration of post-treatment prophylaxis and late recrudescent
infections. The proportionate relationship between asexual stages and
gametocytes does not appear to differ between primary and recurrent
