Publication: Primaquine radical cure of Plasmodium vivax: a critical review of the literature
1
Accepted Date
2012-08-08
Issued Date
2012-08-17
Copyright Date
2012
Resource Type
Language
eng
ISSN
1475-2875 (electronic)
Rights
Mahidol University
Rights Holder(s)
BioMed Central
Bibliographic Citation
John GK, Douglas NM, von Seidlein L, Nosten F, Baird JK, White NJ, et al. Primaquine radical cure of Plasmodium vivax: a critical review of the literature. Malar J. 2012 Aug 17;11:280.
Suggested Citation
John, George K., Douglas, Nicholas M., Seidlein, Lorenz von, Nosten, Francois, Baird, J. Kevin, White, Nicholas J., Price, Ric N. Primaquine radical cure of Plasmodium vivax: a critical review of the literature. John GK, Douglas NM, von Seidlein L, Nosten F, Baird JK, White NJ, et al. Primaquine radical cure of Plasmodium vivax: a critical review of the literature. Malar J. 2012 Aug 17;11:280.. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/704
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Title
Primaquine radical cure of Plasmodium vivax: a critical review of the literature
Corresponding Author(s)
Abstract
BACKGROUND: Primaquine has been the only widely available hypnozoitocidal
anti-malarial drug for half a century. Despite this its clinical efficacy is
poorly characterized resulting in a lack of consensus over the optimal regimen
for the radical cure of Plasmodium vivax.
METHODS: Published studies since 1950 of the use of primaquine regimens for
preventing P. vivax relapse were reviewed. Data were extracted systematically
from available papers. Primaquine regimens were categorized according to the
total dose administered: very low (≤2.5 mg/kg), low (>2.5 mg/kg- < 5.0 mg/kg) and
high (≥ 5.0 mg/kg). The risk of recurrent infection were summarized across
geographical regions and the odds ratios between treatment regimens calculated
after stratifying by total treatment dose and duration of study follow up.
RESULTS: Data could be retrieved from 87 clinical trials presenting data in
59,735 patients enrolled into 156 treatment arms, conducted in 20 countries.
There was marked heterogeneity in study design, particularly primaquine dosing
and duration of follow up. The median rate of recurrence following very low dose
of primaquine (n = 44) was 25% (range 0-90%) at 4-6 months, compared to 6.7 %
(range 0-59%) following low dose primaquine (n = 82). High dose primaquine
regimens were assessed in 28 treatment arms, and were associated with a median
recurrence rate of 0% (Range: 0-15%) at one month. In 18 studies with control
arms, the effectiveness of a very low dose primaquine regimen was no different
from patients who did not receive primaquine (OR = 0.60, 95%CI 0.33-1.09,
p = 0.09), whereas for the low dose regimens a significant difference was
reported in 50% (6/12) of studies (overall OR = 0.14, 95%CI: 0.06-0.35,
p < 0.001). Two studies enrolling 171 patients demonstrated high effectiveness of
high dose primaquine compared to a control arm (OR = 0.03 (95%CI: 0.01-0.13);
p < 0.0001).
CONCLUSIONS: Low dose regimens retain adequate efficacy in some areas, but this
is not uniform. The efficacy and safety of pragmatic high dose primaquine
regimens needs to be assessed in a range of endemic and geographical locations.
Such studies will require a prolonged period of follow up and comparison with
control arms to account for confounding factors.