A review of the WHO malaria rapid diagnostic test product testing programme (2008-2018): performance, procurement and policy

Abstract

Malaria rapid diagnostic tests (RDTs) emerged in the early 1990s into largely unregulated markets, and uncertain field performance was a major concern for the acceptance of tests for malaria case management. This, combined with the need to guide procurement decisions of UN agencies and WHO Member States, led to the creation of an independent, internationally coordinated RDT evaluation programme aiming to provide comparative performance data of commercially available RDTs. Products were assessed against Plasmodium falciparum and Plasmodium vivax samples diluted to two densities, along with malaria-negative samples from healthy individuals, and from people with immunological abnormalities or non-malarial infections. Three measures were established as indicators of performance, (i) panel detection score (PDS) determined against low density panels prepared from P. falciparum and P. vivax wild-type samples, (ii) false positive rate, and (iii) invalid rate, and minimum criteria defined. Over eight rounds of the programme, 332 products were tested. Between Rounds 1 and 8, substantial improvements were seen in all performance measures. The number of products meeting all criteria increased from 26.8% (11/41) in Round 1, to 79.4% (27/34) in Round 8. While products submitted to further evaluation rounds under compulsory re-testing did not show improvement, those voluntarily resubmitted showed significant increases in P. falciparum (p = 0.002) and P. vivax PDS (p < 0.001), with more products meeting the criteria upon re-testing. Through this programme, the differentiation of products based on comparative performance, combined with policy changes has been influential in the acceptance of malaria RDTs as a case-management tool, enabling a policy of parasite-based diagnosis prior to treatment. Publication of product testing results has produced a transparent market allowing users and procurers to clearly identify appropriate products for their situation, and could form a model for introduction of other, broad-scale diagnostics.

Keywords: Malaria; Plasmodium falciparum; Plasmodium vivax; Product improvement; Rapid diagnostic tests.

Fig. 1

Timeline for WHO malaria RDT product testing program (PT). Number of products tested in each round, along with number of expressions of interest (italics). Solid blue arrows represent start of product testing round; open blue arrows represent response to corresponding expression of interest for rounds where expressions of interest exceeded testing capacity. WPRO WHO Regional Office for the Western Pacific, RITM Research Institute for Tropical Medicine, HTD Hospital for Tropical Diseases, IPC/CNM Institut Pasteur du Cambodge/Cambodian National Malaria Centre, KEMRI Kenya Medical Research Institute, TDR Special Programme for Research and Training in Tropical Diseases, CDC US Centers for Disease Control and Prevention, MPAC Malaria Policy Advisory Committee

Fig. 2

Classification of detected and undetected 200 parasite/µL samples (Adapted from the round 6 product testing report [33])

Fig. 3

Proportion of P. falciparum detecting (top) and P. vivax detecting (bottom) products in each panel detection score category in rounds 1–8 of product testing. Bars are shaded according to the product PDS: white represents < 50%, grey: 50–74% and black, ≥ 75% (which meets the WHO recommended performance criteria). Rd round

Fig. 4

False positivity rates for products submitted to rounds 1–8. Bars are shaded according to the product false positivity rate on clean negative samples: white represents ≥ 10%, light grey: 5–9%, dark grey 2–4% and black < 2%. Only products ≥ 10% (white bars) do not meet the WHO performance criteria. Rd round

Fig. 5

Proportion of products fulfilling WHO recommended performance criteria in each round of evaluation. Separate lines are shown for P. falciparum only detecting products (black circles), and combination products (red squares). One pan-only RDT assessed in Round 2, two pan-only RDTs evaluated in Round 5, two pan-only RDTs evaluated in Round 8, and one P. vivax-only RDT assessed in Round 2 met the WHO procurement criteria, but are not included in the figure. Rd round. Products are assessed against P. falciparum and P. vivax samples diluted to 200 parasites/µL