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Dengue virus neutralizing antibody levels associated with protection from infection in thai cluster studies.

Buddhari D, Aldstadt J, Endy TP, Srikiatkhachorn A, Thaisomboonsuk B, Klungthong C, Nisalak A, Khuntirat B, Jarman RG, Fernandez S, Thomas SJ, Scott TW, Rothman AL, Yoon IK - PLoS Negl Trop Dis (2014)

Bottom Line: Comparing subjects exposed to the same serotype, receiver operating characteristic (ROC) curves identified homotypic PRNT titers of 11, 323 and 16 for DENV-1, -2 and -4, respectively, to differentiate "susceptible" from "non-susceptible" subjects.Protective NTs appeared to be serotype-dependent and may be higher for DENV-2 than other serotypes.These findings are relevant for both dengue epidemiology studies and vaccine development efforts.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

ABSTRACT

Background: Long-term homologous and temporary heterologous protection from dengue virus (DENV) infection may be mediated by neutralizing antibodies. However, neutralizing antibody titers (NTs) have not been clearly associated with protection from infection.

Methodology/principal findings: Data from two geographic cluster studies conducted in Kamphaeng Phet, Thailand were used for this analysis. In the first study (2004-2007), cluster investigations of 100-meter radius were triggered by DENV-infected index cases from a concurrent prospective cohort. Subjects between 6 months and 15 years old were evaluated for DENV infection at days 0 and 15 by DENV PCR and IgM ELISA. In the second study (2009-2012), clusters of 200-meter radius were triggered by DENV-infected index cases admitted to the provincial hospital. Subjects of any age ≥6 months were evaluated for DENV infection at days 0 and 14. In both studies, subjects who were DENV PCR positive at day 14/15 were considered to have been "susceptible" on day 0. Comparison subjects from houses in which someone had documented DENV infection, but the subject remained DENV negative at days 0 and 14/15, were considered "non-susceptible." Day 0 samples were presumed to be from just before virus exposure, and underwent plaque reduction neutralization testing (PRNT). Seventeen "susceptible" (six DENV-1, five DENV-2, and six DENV-4), and 32 "non-susceptible" (13 exposed to DENV-1, 10 DENV-2, and 9 DENV-4) subjects were evaluated. Comparing subjects exposed to the same serotype, receiver operating characteristic (ROC) curves identified homotypic PRNT titers of 11, 323 and 16 for DENV-1, -2 and -4, respectively, to differentiate "susceptible" from "non-susceptible" subjects.

Conclusions/significance: PRNT titers were associated with protection from infection by DENV-1, -2 and -4. Protective NTs appeared to be serotype-dependent and may be higher for DENV-2 than other serotypes. These findings are relevant for both dengue epidemiology studies and vaccine development efforts.

No MeSH data available.


Related in: MedlinePlus

Receiver operating characteristic (ROC) curves for homotypic neutralizing antibody titers (NTs) against reference strains.Curves discriminate between dengue virus (DENV) PCR positive and negative subjects for: (a) all serotypes combined; (b) DENV-1; (c) DENV-4; (d) DENV-2.
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pntd-0003230-g004: Receiver operating characteristic (ROC) curves for homotypic neutralizing antibody titers (NTs) against reference strains.Curves discriminate between dengue virus (DENV) PCR positive and negative subjects for: (a) all serotypes combined; (b) DENV-1; (c) DENV-4; (d) DENV-2.

Mentions: When all serotypes were combined, PCR status was significantly associated with the log of homotypic NT both alone and adjusted for age (Table 2). ROC curves were created for all serotypes combined, and for each serotype separately (Figure 4). Considering subjects from just DENV-1 clusters, age-adjusted models to predict PCR status were better (based on AIC and AUC) when using homotypic DENV-1 NTs (AUC = 0.833 [95% CI 0.590, 1.000]) than heterotypic NTs (Table 3). For DENV-4 clusters, age-adjusted models were better using homotypic DENV-4 NTs (AUC = 0.889 [95% CI 0.667, 1.000]) than heterotypic NTs (Table 3). For DENV-2 clusters, age-adjusted models were better using both homotypic DENV-2 reference NTs (AUC = 0.740 [95% CI 0.460, 0.960]) and heterotypic DENV-4 reference NTs (AUC = 0.880 [95% CI 0.680, 1.000]) than other heterotypic NTs (Table 3). When different DENV-2 strains were used for PRNT, the AUC using Asian I 1974 strain appeared to have the best fit. The AUC using DENV-2 homologous virus was comparable to that using DENV-2 reference strain.


Dengue virus neutralizing antibody levels associated with protection from infection in thai cluster studies.

Buddhari D, Aldstadt J, Endy TP, Srikiatkhachorn A, Thaisomboonsuk B, Klungthong C, Nisalak A, Khuntirat B, Jarman RG, Fernandez S, Thomas SJ, Scott TW, Rothman AL, Yoon IK - PLoS Negl Trop Dis (2014)

Receiver operating characteristic (ROC) curves for homotypic neutralizing antibody titers (NTs) against reference strains.Curves discriminate between dengue virus (DENV) PCR positive and negative subjects for: (a) all serotypes combined; (b) DENV-1; (c) DENV-4; (d) DENV-2.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4199527&req=5

pntd-0003230-g004: Receiver operating characteristic (ROC) curves for homotypic neutralizing antibody titers (NTs) against reference strains.Curves discriminate between dengue virus (DENV) PCR positive and negative subjects for: (a) all serotypes combined; (b) DENV-1; (c) DENV-4; (d) DENV-2.
Mentions: When all serotypes were combined, PCR status was significantly associated with the log of homotypic NT both alone and adjusted for age (Table 2). ROC curves were created for all serotypes combined, and for each serotype separately (Figure 4). Considering subjects from just DENV-1 clusters, age-adjusted models to predict PCR status were better (based on AIC and AUC) when using homotypic DENV-1 NTs (AUC = 0.833 [95% CI 0.590, 1.000]) than heterotypic NTs (Table 3). For DENV-4 clusters, age-adjusted models were better using homotypic DENV-4 NTs (AUC = 0.889 [95% CI 0.667, 1.000]) than heterotypic NTs (Table 3). For DENV-2 clusters, age-adjusted models were better using both homotypic DENV-2 reference NTs (AUC = 0.740 [95% CI 0.460, 0.960]) and heterotypic DENV-4 reference NTs (AUC = 0.880 [95% CI 0.680, 1.000]) than other heterotypic NTs (Table 3). When different DENV-2 strains were used for PRNT, the AUC using Asian I 1974 strain appeared to have the best fit. The AUC using DENV-2 homologous virus was comparable to that using DENV-2 reference strain.

Bottom Line: Comparing subjects exposed to the same serotype, receiver operating characteristic (ROC) curves identified homotypic PRNT titers of 11, 323 and 16 for DENV-1, -2 and -4, respectively, to differentiate "susceptible" from "non-susceptible" subjects.Protective NTs appeared to be serotype-dependent and may be higher for DENV-2 than other serotypes.These findings are relevant for both dengue epidemiology studies and vaccine development efforts.

View Article: PubMed Central - PubMed

Affiliation: Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

ABSTRACT

Background: Long-term homologous and temporary heterologous protection from dengue virus (DENV) infection may be mediated by neutralizing antibodies. However, neutralizing antibody titers (NTs) have not been clearly associated with protection from infection.

Methodology/principal findings: Data from two geographic cluster studies conducted in Kamphaeng Phet, Thailand were used for this analysis. In the first study (2004-2007), cluster investigations of 100-meter radius were triggered by DENV-infected index cases from a concurrent prospective cohort. Subjects between 6 months and 15 years old were evaluated for DENV infection at days 0 and 15 by DENV PCR and IgM ELISA. In the second study (2009-2012), clusters of 200-meter radius were triggered by DENV-infected index cases admitted to the provincial hospital. Subjects of any age ≥6 months were evaluated for DENV infection at days 0 and 14. In both studies, subjects who were DENV PCR positive at day 14/15 were considered to have been "susceptible" on day 0. Comparison subjects from houses in which someone had documented DENV infection, but the subject remained DENV negative at days 0 and 14/15, were considered "non-susceptible." Day 0 samples were presumed to be from just before virus exposure, and underwent plaque reduction neutralization testing (PRNT). Seventeen "susceptible" (six DENV-1, five DENV-2, and six DENV-4), and 32 "non-susceptible" (13 exposed to DENV-1, 10 DENV-2, and 9 DENV-4) subjects were evaluated. Comparing subjects exposed to the same serotype, receiver operating characteristic (ROC) curves identified homotypic PRNT titers of 11, 323 and 16 for DENV-1, -2 and -4, respectively, to differentiate "susceptible" from "non-susceptible" subjects.

Conclusions/significance: PRNT titers were associated with protection from infection by DENV-1, -2 and -4. Protective NTs appeared to be serotype-dependent and may be higher for DENV-2 than other serotypes. These findings are relevant for both dengue epidemiology studies and vaccine development efforts.

No MeSH data available.


Related in: MedlinePlus