A measles IgM rapid diagnostic test to address challenges with national measles surveillance and response in Malaysia.

A lateral flow rapid diagnostic test (RDT) enables detection of measles specific immunoglobulin M (IgM) antibody in serum, capillary blood, and oral fluid with accuracy consistent with enzyme immunoassay (EIA). The objectives of the study were: 1) to assess measles RDT inter-reader agreement between two clinic staff; 2) to assess the sensitivity and specificity of the measles RDT relative to standard surveillance testing in a low transmission setting; 3) to evaluate the knowledge, attitudes, and practices of staff in clinics using the RDT; and 4) to assess the impact of RDT testing on the measles public health response in Malaysia. The clinic-based prospective evaluation included all suspected measles cases captured by routine measles surveillance at 34 purposely selected clinics in 15 health districts in Malaysia between September 2019 and June 2020, following day-long regional trainings on RDT use. Following informed consent, four specimens were collected from each suspected case, including those routinely collected for standard surveillance [serum for EIA and throat swabs for quantitative reverse transcriptase polymerase chain reaction (RT-qPCR)] together with capillary blood and oral fluid tested with RDTs during the study. RDT impact was evaluated by comparing the rapidity of measles public health response between the pre-RDT implementation (December 2018 to August 2019) and RDT implementation periods (September 2019 to June 2020). To assess knowledge, attitudes, and practices of RDT use, staff involved in the public health management of measles at the selected sites were surveyed. Among the 436 suspect cases, agreement of direct visual readings of measles RDT devices between two health clinic staff was 99% for capillary blood (k = 0.94) and 97% for oral fluid (k = 0.90) specimens. Of the total, 45 (10%) were positive by measles IgM EIA (n = 44, including five also positive by RT-qPCR) or RT-qPCR only (n = 1), and 38 were positive by RDT (using either capillary blood or oral fluid). Using measles IgM EIA or RT-qPCR as reference, RDT sensitivity using capillary blood was 43% (95% CI: 30%-58%) and specificity was 98% (95% CI: 96%-99%); using oral fluid, sensitivity (26%, 95% CI: 15%-40%) and specificity (97%, 95% CI: 94%-98%) were lower. Nine months after training, RDT knowledge was high among staff involved with the public health management of measles (average quiz score of 80%) and was highest among those who received formal training (88%), followed by those trained during supervisory visits (83%). During the RDT implementation period, the number of days from case confirmation until initiation of public response decreased by about 5 days. The measles IgM RDT shows >95% inter-reader agreement, high retention of RDT knowledge, and a more rapid public health response. However, despite ≥95% RDT specificity using capillary blood or oral fluid, RDT sensitivity was <45%. Higher-powered studies using highly specific IgM assays and systematic RT-qPCR for case confirmation are needed to establish the role of RDT in measles elimination settings.

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During the project, LW and DWB were supported in part by Bill & Melinda Gates grant number OPP1066619 to develop the measles IgM RDT and the ‘Oralight’ oral fluid collection device. The ‘Oralight’ oral fluid collection device is the subject of patent application PCT/GB2015/051155 by Public Health England (PHE; now UKHSA), with priority date 17 April 2014, and currently undergoing patent prosecution in US, Japan, Canada, Australia, India and Europe. The rapid diagnostic test has been licensed non-exclusively from UKHSA to Global Access Diagnostics (GADx) Ltd, England. A modified version of this device is being developed for regulatory approval and commercialization by GADx and Diatropix, a not-for-profit initiative of Institut Pasteur de Dakar, Senegal, with funding from Bill & Melinda Gates Foundation, Seattle, WA (grant number INV-003213). LW is employed by UKHSA that has been sub-contracted by Institut Pasteur de Dakar to support the technical transfer of measles RDT technology from UKHSA to GADx, and DWB holds a fellowship at Fiocruz in Brazil funded with this grant support. These circumstances do not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors declared that no competing interests exist. Besides the BMGF grant, there was no other external funding received for this study. BMGF had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.