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Relationships between flavivirus serological laboratory test results from dengue endemic areas of India: Limitations and challenges

2016; Elsevier BV; Volume: 45; Linguagem: Inglês

10.1016/j.ijid.2016.02.482

1878-3511

Joshua Nealon, Anita Chakravarti, Annick Moureau, Suman Kumar, R. Leon Ochiai, Matthew Bonaparte, Suneela Garg,

Malaria Research and Control

Background: Cross-sectional, population-based seroprevalence studies provide data on exposure to pathogens, susceptibility and disease transmission dynamics, and are useful in public health and vaccination planning. Cross-reactivity between flavivirus IgG antibody assays is an important consideration where multiple flaviviruses co-circulate. Methods & Materials: An age-stratified dengue and Japanese encephalitis virus (JEV) IgG seroprevalence study was conducted in 8 sites across India, enrolling 2,591 subjects aged 5 – 10 years. Sera were tested using commercial ELISA kits; those dengue positive were subjected to plaque reduction neutralization test (PRNT) for serotype-specific neutralizing antibodies (DEN-1, 2, 3 and 4). A threshold of ≥ 10 (1/dil) was considered detectable; an algorithm was applied to interpret profiles as "naïve", "monotypic" or "multitypic". This secondary analysis explored a hypothesis that JEV IgG status was associated with cross-reactive dengue antibodies. JEV IgG results were analyzed by: a) dengue IgG status; b) naïve/monotypic/multitypic PRNT profile; c) the number of serotypes with detectable neutralizing antibodies; and d) geometric mean neutralizing antibody titer (GMT). Associations were tested by Pearson's chi squared test. Results: Overall, 1,525/2,558 (59.6%) of available samples were dengue IgG positive, and 345/2,544 (13.6%) were positive for JEV IgG. Of JEV positive samples, 327 (94.8%) were also dengue IgG positive. Similarly, 96.5% of the 405 "inconclusive" JEV samples were dengue positive. Of the 1,794 JEV IgG negative samples, 801 (44.6%) were dengue IgG positive (p<0.0001). Examining PRNT profiles, 0.62%, 25.3% and 74.1% of JEV positive samples were naïve, monotypic and multitypic, compared to 4.5%, 38.6% and 56.9% of JEV negative subjects (p<0.0001). 97.8% of the JEV positive and 92.5% of inconclusive samples had detectable titres against all four dengue serotypes, compared with 71.0% of the JEV negative samples. For every monotypic dengue serotype, the GMT was highest in JEV positive subjects, followed by those with an inconclusive JEV result, and lowest in the JEV negative group. Conclusion: While limited by a lack of PRNT data from dengue IgG negative subjects, these results suggest that JEV IgG ELISA test results in dengue-endemic areas should be viewed with caution. More specific laboratory methods, such as JEV PRNT, should be employed where available.