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

Abstract

IntroductionRecurrent 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.MethodsA 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.ResultsSince 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.ConclusionsOver 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.

Population Pharmacokinetics and Pharmacodynamics of Chloroquine in a Plasmodium vivax Volunteer Infection Study

“…Chloroquine resistance to P. vivax emerged in Papua New Guinea in the late 1980s, 2,3 and evidence of reduced chloroquine efficacy has been reported in other malaria endemic countries. 4,5 Evaluating the efficacy of antimalarial drugs in P. vivax malaria is difficult due to lack of a continuous in vitro P. vivax culture system, and by the inability of molecular genotyping to discriminate between recrudescence (i.e., blood-stage treatment failures), relapse, and new infections.…”

Comparison of the Cumulative Efficacy and Safety of Chloroquine, Artesunate, and Chloroquine-Primaquine in Plasmodium vivax Malaria

“…As G6PD deficiency is common in tropical regions and testing is seldom available, radical-cure PMQ regimens are often not given despite being widely recommended. For nearly 70 years the standard treatment for P. vivax malaria has been chloroquine (CQ), although resistance is increasing in many areas [ 3 ]. Chloroquine is eliminated slowly, resulting in posttreatment suppression of emerging P. vivax malaria recurrences for over a month following treatment.…”

Plasmodium vivax Infection in Duffy-Negative People in Africa

“…Taken together, available reports continue to document the emerging perspective of wide-spread infection of Duffy-negative populations with P. vivax . Going forward, it will be of interest to malaria researchers to continue updating the global map of P. vivax to refine what we understand about the geographical range of this parasite, 11 drug resistance genotypes and phenotypes, 12 naturally occurring variation in its RBC invasion protein repertoire, 13 – 17 and the human and nonhuman primate hosts it infects. 18 , 19 Recent studies have added significantly to the map of global P. vivax distribution 20 and provided a focused assessment of this parasite in Africa.…”