The Vivax Surveyor: Online mapping database for Plasmodium vivax clinical trials

Abstract

Introduction: Recurrent P. vivax infections are associated with significant morbidity and mortality. Although radical cure can reduce recurrent infection, it is confounded by antimalarial resistance and the lack of safe and effective hypnozoitocidal treatment. This study documents the available literature of published clinical trials of P. vivax, providing an up to date, online, open access tool to view and download available information.

Methods: A systematic review was conducted according to PRISMA guidelines to identify prospective P. vivax therapeutic clinical trials with at least 28 days follow-up published between 1st January 1960 and 12th October 2016. Treatment arms and evidence of chloroquine resistance were mapped to trial sites.

Results: Since 1960, a total of 1152 antimalarial clinical trials with a minimum 28 days follow-up have been published, of which 230 (20.0%) enrolled patients with P. vivax and were included. Trials were conducted in 38 countries: 168 (73.0%) in the Asia-Pacific, 13 (5.7%) in Africa and 43 (18.7%) in the Americas. The proportion of antimalarial trials assessing P. vivax rose from 10.7% (12/112) in 1991-1995, to 24.9% (56/225) in 2011-2015. Overall, 188 (81.7%) P. vivax trials included a chloroquine treatment arm, either alone or in combination with primaquine, and 107 (46.5%) trials included a chloroquine treatment arm with early primaquine to assess radical cure. There has been a recent increase in treatment arms with artemisinin derivatives. Of the 131 sites in which chloroquine resistance could be quantified, resistance was present in 59 (45.0%) sites in 15 endemic countries.

Conclusions: Over the last 20 years there has been a substantial increase in clinical research on the treatment of P. vivax, which has generated a greater awareness of the global extent of chloroquine resistance. The WWARN open access, online interactive map provides up to date information of areas where drug resistant P. vivax is emerging.

Keywords: Clinical trial; Open access; Plasmodium vivax; Resistance; Review; Treatment.

Graphical abstract

Fig. 1

Trial selection.

Fig. 2

Number of clinical trials of P. vivax monoinfection published each year according to region.

Fig. 3

Temporal trends in the percentage of all antimalarial clinical efficacy trials that include patients with P. vivax monoinfection, by region.

Fig. 4

Duration of follow up in P. vivax clinical trials.

Fig. 5

Temporal trends in the proportion of P. vivax clinical trials assessing efficacy of chloroquine monotherapy or chloroquine combined with early primaquine.

Fig. 6

Vivax Surveyor map (www.wwarn.org/vivax/surveyor/) identifying trial sites where chloroquine resistance has been identified in clinical efficacy trials of P. vivax monoinfection (WorldWide Antimalarial Resistance Network, 2016a).

Fig. 7

Map of 45 countries reporting indigenous P. vivax during 2015 – categorised according to published clinical trial information or WHO recorded therapeutic efficacy studies assessing chloroquine efficacy since 1 January 2011. Green - Both published clinical trials and WHO recorded therapeutic efficacy studies assessing chloroquine efficacy against P. vivax since 1 January 2011; Yellow - Published clinical trials but no WHO recorded therapeutic efficacy studies assessing chloroquine efficacy against P. vivax since 1 January 2011; Orange - WHO recorded therapeutic efficacy studies but no published clinical trials assessing chloroquine efficacy against P. vivax since 1 January 2011; Red – No published clinical trials nor WHO recorded therapeutic efficacy studies assessing chloroquine efficacy against P. vivax since 1January 2011. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)