TY - JOUR
T1 - Inferring the serotype associated with dengue virus infections on the basis of pre- and postinfection neutralizing antibody titers
AU - Van Panhuis, Willem G.
AU - Gibbons, Robert V.
AU - Endy, Timothy P.
AU - Rothman, Alan L.
AU - Srikiatkhachorn, Anon
AU - Nisalak, Ananda
AU - Burke, Donald S.
AU - Cummings, Derek A.T.
N1 - Funding Information:
Received 20 January 2010; accepted 27 April 2010; electronically published 25 August 2010. The opinions expressed are those of the authors and do not represent the official views of the National Institutes of Health or the US Department of Defense. Potential conflicts of interest: none reported. Presented in part: 58th annual meeting of the American Society of Tropical Medicine and Hygiene, Washington, D.C., 19 November 2009 (abstract 32). Financial support: The Bill & Melinda Gates Foundation (W.G.v.P., D.S.B., and D.A.T.C); National Institutes of Health (grants 1U01-GM070708 [to D.S.B. and D.A.T.C], 1R01 TW008246-01 [to D.A.T.C.], and NIH P01 AI034533 [to R.V.G., T.P.E., A.L.R., and A.N.]); the Burroughs Wellcome Fund (Career Award at the Scientific Interface [to D.A.T.C.]); and the US Military Infectious Disease Research Program. Reprints or correspondence: Willem G. van Panhuis, 127 Parran Hll, 130 DeSoto St, Pittsburgh, PA 15261 (wav10@pitt.edu).
PY - 2010/10/1
Y1 - 2010/10/1
N2 - Background. Currently, the only tests capable of determining the serotype associated with dengue virus (DENV) infection require sampling during the period of acute viremia. No test can accurately detect the serotype associated with past DENV infections. The standard assay for determination of serotype-specific antibody against DENV is the plaque reduction neutralization test (PRNT), although performance of this test continues to be evaluated. Methods. From a cohort study among schoolchildren in Thailand, PRNT values were determined in serum samples collected before and after infection. A multinomial logistic regression model was used to infer the serotype associated with intercurrent DENV infections. Models were validated based on polymerase chain reaction identification of DENV serotypes. Results. The serotype associated with DENV infection inferred by the model corresponded with polymerase chain reaction in 67.6% of cases, and the k statistic was 0.479. A model for 35 cases with primary seroconversion correctly identified the DENV serotypes causing infection in 77.1% of cases, compared with 66.9%, using a model for 169 cases with secondary seroconversion. The best model using only postinfection PRNT values correctly inferred the DENV serotype causing infection in 60.3% of cases. Conclusions. A statistical model based on both pre- and postinfection PRNT values can be used to infer the serotype associated with DENV infections in prospective studies and vaccine trials.
AB - Background. Currently, the only tests capable of determining the serotype associated with dengue virus (DENV) infection require sampling during the period of acute viremia. No test can accurately detect the serotype associated with past DENV infections. The standard assay for determination of serotype-specific antibody against DENV is the plaque reduction neutralization test (PRNT), although performance of this test continues to be evaluated. Methods. From a cohort study among schoolchildren in Thailand, PRNT values were determined in serum samples collected before and after infection. A multinomial logistic regression model was used to infer the serotype associated with intercurrent DENV infections. Models were validated based on polymerase chain reaction identification of DENV serotypes. Results. The serotype associated with DENV infection inferred by the model corresponded with polymerase chain reaction in 67.6% of cases, and the k statistic was 0.479. A model for 35 cases with primary seroconversion correctly identified the DENV serotypes causing infection in 77.1% of cases, compared with 66.9%, using a model for 169 cases with secondary seroconversion. The best model using only postinfection PRNT values correctly inferred the DENV serotype causing infection in 60.3% of cases. Conclusions. A statistical model based on both pre- and postinfection PRNT values can be used to infer the serotype associated with DENV infections in prospective studies and vaccine trials.
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U2 - 10.1086/656141
DO - 10.1086/656141
M3 - Article
C2 - 20738205
AN - SCOPUS:77956900045
SN - 0022-1899
VL - 202
SP - 1002
EP - 1010
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 7
ER -