Biology Reference
In-Depth Information
combination therapy was chosen for demonstration purposes because it
is highly effective for eliminating the blood stages of both
P. vivax
and
P. falciparum
(thus minimising the risk of recrudescence) and is cleared rela-
tively rapidly from the bloodstream (
t
1/2
for artesunate is approximately
30 min and for lumefantrine is approximately 3.2 days). The latter property
ensures that concentrations of the drugs will be negligible by day 16, well
before the first
P. vivax
relapse is likely to appear (approximately day 21
for tropical strains). In Myanmar, 45% of patients treated for
P. falciparum
monoinfections with AM + LUM had a recurrence of
P. vivax
by day 63
(
Smithuis et al., 2010
). On the Thai-Myanmar border, the corresponding
proportion at day 63 following AM + LUM was 53.8% (
Douglas et al.,
2011
) and in Papua, New Guinea, at day 42 was 64.7% (
Karunajeewa et al.,
2008
). These proportions far exceeded basal
P. vivax
infection rates in the
respective study locations and given the potency of both artesunate and
lumefantrine against
P. vivax
, the recurrences were very unlikely to have
been recrudescences from sub-patent
P. vivax
blood-stage infections. In
many of these studies, the risk of
P. vivax
following
P. falciparum
malaria was
greater than the rate of
P. falciparum
failure and, therefore, the most com-
monly transmitted parasite following falciparum malaria, paradoxically, was
P. vivax
(median percentage of recurrences due to
P. vivax
= 51%, range
7.7-100%)
.
The most likely explanation for heterologous
P. vivax
relapse is that the
physiological derangement associated with falciparum malaria awakens
dormant hypnozoites acquired during previous
P. vivax
infections (
White,
2011
;
Douglas et al., 2011
;
Looareesuwan et al., 1987
). Alternatively, heter-
ologous
P. vivax
relapses may arise from simultaneous
P. vivax
inoculations
that never reach patency (
Douglas et al., 2011
;
Looareesuwan et al., 1987
).
Whatever the cause,
P. vivax
infection following falciparum malaria carries
significant morbidity and is likely to have an important role in sustaining
P. vivax
transmission in co-endemic regions (
Douglas et al., 2011
). Modi-
fying the probability that
P. vivax
relapse occurs should, therefore, be an
important consideration in
P. falciparum
as well as
P. vivax
malaria therapy.
3. REDUCING
P.VIVAX
TRANSMISSION BY TREATING
SYMPTOMATIC DISEASE
A primary opportunity to reduce total parasitaemia associated with
a
P. vivax
inoculation is the point at which a patient presents with symp-
tomatic infection. There are three aspects to acute treatment of vivax
