title: Clinical validation of a point-of-care multiplexed in vitro immunoassay using monoclonal antibodies (the MSD influenza test) in four hospitals in Vietnam.
abstract: Point-of-care (POC) diagnostic tests for influenza can considerably shorten the time to clinical decision making. An investigational POC test based on a multiplexed immunoassay was developed by Meso Scale Diagnostics, LLC (MSD), with the objective to make a more sensitive rapid test that can also subtype influenza A viruses (1977 H1, H3, and H5). Between February and November 2010, we conducted a prospective multicenter study at four hospitals in Vietnam and compared the performance of this test to that of the WHO/CDC real-time reverse transcriptase PCR (RT-PCR) on nasal and throat swab specimens from patients presenting with influenza-like illness. Five hundred sixty-three adults and children with a median age of 25 months were enrolled. Sensitivity and specificity of the test with combined results from nasal and throat swab samples were 74.0% (131/177) and 99.7% (351/352), respectively, compared to RT-PCR. The POC test was as sensitive for influenza virus B as for influenza virus A (74.4% [64/86] versus 73.6% [67/91]). The positivity rate was associated with lower cycle threshold values (a marker for higher viral loads), sample type (73.6% for nasal swab versus 52.4% for throat swab), and younger age. A total of 210 (18.7%) out of 1,126 MSD tests failed, and for 34 (6%) of patients, both test samples failed (these were excluded from the performance analysis). Subtyping could be assessed only for influenza virus A/H3N2, as 1977 H1N1 was not circulating at the time and no H5N1-infected patients were enrolled, and was successful only in 9/54 patients infected with H3 influenza virus who had a positive POC test result for influenza virus A. This novel POC test provided highly sensitive detection of influenza viruses A and B compared to the reported sensitivities of other rapid tests. However, 18.7% of tests failed for technical reasons and subtyping for H3 was poor. Drawbacks to the technology include the requirement for a dedicated reader instrument and the need for continual updating of subtyping antibodies within the test array.
authors.affiliation: South East Asian Infectious Diseases Clinical Research Network, Ho Chi Minh City, Vietnam. hrogier@gmail.com
authors.forename: H Rogier
authors.initials: HR
authors.lastname: van Doorn
authors.forename: Nguyen van
authors.initials: Nv
authors.lastname: Kinh
authors.forename: Ha Manh
authors.initials: HM
authors.lastname: Tuan
authors.forename: Tran Anh
authors.initials: TA
authors.lastname: Tuan
authors.forename: Ngo Ngoc Quang
authors.initials: NN
authors.lastname: Minh
authors.forename: Juliet E
authors.initials: JE
authors.lastname: Bryant
authors.forename: Vu thi Ty
authors.initials: Vt
authors.lastname: Hang
authors.forename: Le thi Tham
authors.initials: le TT
authors.lastname: Uyen
authors.forename: Le Quoc
authors.initials: le Q
authors.lastname: Thinh
authors.forename: Tran thi Ngoc
authors.initials: Tt
authors.lastname: Anh
authors.forename: Nguyen Phu Huong
authors.initials: NP
authors.lastname: Lan
authors.forename: Nguyen Vu
authors.initials: NV
authors.lastname: Trung
authors.forename: Walter
authors.initials: W
authors.lastname: Taylor
authors.forename: Laura
authors.initials: L
authors.lastname: Merson
authors.forename: Heiman F L
authors.initials: HF
authors.lastname: Wertheim
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.forename: Marcel
authors.initials: M
authors.lastname: Wolbers
authors.forename: Nguyen van Vinh
authors.initials: Nv
authors.lastname: Chau
authors.forename: Menno D
authors.initials: MD
authors.lastname: de Jong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral / Q000032:analysis* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006761:Hospitals; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007223:Infant; D007251:Influenza, Human / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009975:Orthomyxoviridae / Q000145:classification / Q000276:immunology / Q000302:isolation & purification*; D019095:Point-of-Care Systems; D012680:Sensitivity and Specificity; D014744:Vietnam; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral