Performance of virus isolation and Directigen (R) Flu A to detect influenza A virus in experimental human infection

Background: few data exist to assess the sensitivity of different specimen types for viral detection during the course of influenza virus infection. O bjectives: this study assessed the relationships between quantitative influ enza A virus replication and antigen detectability by the enzyme immunosorb ent assay (EIA) Directigen(R) Flu A in different type of samples during exp erimental human infection. Study design: fourteen volunteers were inoculate d with influenza A virus A/Texas/36/91 (H1N1). Four specimens types were co llected in sequence for quantitative isolation in cell culture and antigen testing from days 1 to 8 after inoculation. Results: seventy-one (63%) of n asopharyngeal wash specimens were culture positive, compared to 51 (46%) of throat gargles, 51 (46%) of nasal swabs, and 27 (24%) of throat swabs. All subjects shed virus in their nasopharyngeal wash at least one day and 86% of subjects had a positive nasopharyngeal wash culture on day 2 after inocu lation. The mean viral titers were highest on day 2 post inoculation for al l specimen types and averaged 3.6 log(10) TCID50/ml for nasal washes, 1.2 l og(10) TCID50/ml for throat gargles, 1.8 log(10) TCID50/ml for the nasophar yngeal swabs, and 0.6 log(10) TCID50/ml for the throat swabs. Mean viral ti ters in the nasal washes were significantly different (P < 0.05) compared t o other specimen types. The peak of sensitivity of EIA (compared to culture ) was the second day after inoculation. Nasopharyngeal and throat swab resu lts were combined for this analysis and considered positive by culture if p ositive in either or both samples. Thus, on day 2 the number of EIA positiv e samples relative to the number culture positive was 9/12 (75%) for nasoph aryngeal wash specimens, 2/9 (22%) for throat gargles, and 7/11 (64%) for t he combined throat and nasal swabs specimens. Conclusions: nasopharyngeal w ashes are the most sensitive sample type detecting influenza A virus in adu lts. For rapid diagnosis the Directigen(R) Flu A is a an alternative with a sensitivity compared to culture ranging between 64 and 78% if performed on nasopharyngeal specimens on day two or three after experimental infection in adults. However, if performed on other specimens or later in the course of infection the sensitivity is lower. (C) 1999 Published by Elsevier Scien ce B.V. All rights reserved.