Defining the next generation of Plasmodium vivax diagnostic tests for control and elimination: Target product profiles

The global prevalence of malaria has decreased over the past fifteen years, but similar gains have not been realized against Plasmodium vivax because this species is less responsive to conventional malaria control interventions aimed principally at P. falciparum. Approximately half of all malaria cases outside of Africa are caused by P. vivax. This species places dormant forms in human liver that cause repeated clinical attacks without involving another mosquito bite. The diagnosis of acute patent P. vivax malaria relies primarily on light microscopy. Specific rapid diagnostic tests exist but typically perform relatively poorly compared to those for P. falciparum. Better diagnostic tests are needed for P. vivax. To guide their development, FIND, in collaboration with P. vivax experts, identified the specific diagnostic needs associated with this species and defined a series of three distinct target product profiles, each aimed at a particular diagnostic application: (i) point-of-care of acutely ill patients for clinical care purposes; (ii) point-of-care asymptomatic and otherwise sub-patent residents for public health purposes, e.g., mass screen and treat campaigns; and (iii) ultra-sensitive not point-of-care diagnosis for epidemiological research/surveillance purposes. This report presents and discusses the rationale for these P. vivax-specific diagnostic target product profiles. These contribute to the rational development of fit-for-purpose diagnostic tests suitable for the clinical management, control and elimination of P. vivax malaria.
Author summary Plasmodium vivax is the second most prevalent Plasmodium species amongst the five that can infect humans and cause malaria. The control and elimination of P. vivax is complicated by its specific biology, such as hard-to-detect low densities of blood-circulating parasites in infected individuals, the existence of persistent liver forms causing relapse, or the early appearance of sexual stages of the parasite during the course of an infection, which facilitates its transmission. These difficulties are reinforced by the fact that most antimalarial tools have been developed primarily for P. falciparum, the most prevalent malaria species, and are not always as effective for P. vivax. Current tools for the diagnosis of P. vivax are of limited effectiveness. Rapid diagnostic tests exist but show, in average, lower performance than similar test for P. falciparum. P. vivax diagnosis often relies on light microscopy which is challenging to maintain at a high quality and not sensitive enough to detect a large fraction of all infections. Recognizing that better diagnostic tools for P. vivax are needed, we report in this study the development of new target product profiles to define the specific characteristics of such tests. The establishment of these consensus-based documents is an important first step to guide research and development efforts toward better diagnostic solutions for P. vivax malaria and to accelerate the elimination of this species alongside P. falciparum.