A total of 129 clinical trials were included in the analyses.
Figure 1 shows the risk of recurrence at day 28 for patients treated with chloroquine alone and for patients treated with chloroquine and primaquine. A total of 14 studies included patients recruited into comparative studies of chloroquine monotherapy and chloroquine plus primaquine administered at the start of treatment. In all but one of these studies patients receiving chloroquine plus primaquine had an equivalent or lower risk of P. vivax recurrence by day 28. The overall Odds Ratio (OR) was 0.27 (95%CI 0.11-0.70; p=0.007).
The location of study sites with documented chloroquine resistance and chloroquine sensitive P. vivax is shown in Figure 2a and for chloroquine sensitive sites in Figure 2b below. Estimates for chloroquine sensitivity derived from 112 sites. In 50.9% of the sites estimates P. vivax were categorized as resistant. You can download an excel file of the extracted data from the P. vivax antimalarial efficacy study sites.
Fig. 2a legend Red icons = Category 1; Dark Orange = Category 2; Light Orange = Category 3; Yellow = case reports.
Fig. 2b legend Green icons = conducted prior to 2008; Blue icons = conducted between 2008-2014.
Figure 3 shows the proportion of patients with parasites in the peripheral blood stream on day 2 and 3 divided by CQR and CQS based on day 28 recurrence. Site estimates categorized as CQR had significant higher proportions of patients that were parasitaemic on day 2 and 3 compared to those categorized as CQS.
CQR P. vivax poses a significant threat to malaria endemic communities. Enhanced monitoring of P. vivax drug efficacy is needed to adapt treatment policy accordingly. This will require standardised methodologies and the development of novel tools for the more precise quantification of drug efficacy. Figure 4 shows the common causes for misdiagnosis of chloroquine sensitivity and chloroquine resistant P. vivax.
WWARN provides an example of a protocol template for researchers, which we believe addresses the main challenges of P. vivax efficacy monitoring and can be adapted to site specific needs. Download the WHO manual for therapeutic efficacy monitoring, including protocols for the study of P. vivax.
View the abstract: Price RN, von Seidlein L, Valecha N, et al. The global extent of chloroquine resistant plasmodium vivax: a systematic review and meta-analysis. Lancet Infectious Diseases; DOI S1473-3099(14)70855-2.