Dengue Plaque Reduction Neutralization Test (PRNT) in Primary and Secondary Dengue Virus Infections: How Alterations in Assay Conditions Impact Performance

Thomas, Stephen J.; Nisalak, Ananda; Anderson, Kathryn B.; Libraty, Daniel H.; Kalayanarooj, Siripen; Vaughn, David W.; Putnak, Robert; Gibbons, Robert V.; Jarman, Richard G.; Endy, Timothy P.

doi:10.4269/ajtmh.2009.08-0625

Cited by 191 publications

(170 citation statements)

References 34 publications

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“…In Iquitos, people commonly visit other residences, but in other geographic areas, people may be more or less mobile, making the home or other locations comparatively more important for transmission. Our DENV-4 plaque reduction neutralization test (PRNT) had high specificity, but, as for other investigators, sensitivity was low (47). Consequently, we have confidence in our positive results, but false negative results may underestimate seroprevalence.…”

Section: Discussionmentioning

confidence: 83%

House-to-house human movement drives dengue virus transmission

Stoddard

Forshey

Morrison

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

447

425

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Dengue is a mosquito-borne disease of growing global health importance. Prevention efforts focus on mosquito control, with limited success. New insights into the spatiotemporal drivers of dengue dynamics are needed to design improved disease-prevention strategies. Given the restricted range of movement of the primary mosquito vector, Aedes aegypti, local human movements may be an important driver of dengue virus (DENV) amplification and spread. Using contact-site cluster investigations in a case-control design, we demonstrate that, at an individual level, risk for human infection is defined by visits to places where contact with infected mosquitoes is likely, independent of distance from the home. Our data indicate that house-to-house human movements underlie spatial patterns of DENV incidence, causing marked heterogeneity in transmission rates. At a collective level, transmission appears to be shaped by social connections because routine movements among the same places, such as the homes of family and friends, are often similar for the infected individual and their contacts. Thus, routine, house-to-house human movements do play a key role in spread of this vector-borne pathogen at fine spatial scales. This finding has important implications for dengue prevention, challenging the appropriateness of current approaches to vector control. We argue that reexamination of existing paradigms regarding the spatiotemporal dynamics of DENV and other vectorborne pathogens, especially the importance of human movement, will lead to improvements in disease prevention.infectious disease | spatial epidemiology | arthropod-borne virus | emerging infections | disease ecology D engue is a mosquito-borne viral infection prevalent in the tropics and subtropics with an incidence and range that have increased substantially over the last three decades (1-4). The incidence of severe, life-threatening disease (dengue hemorrhagic fever or DHF) is also on the rise (5). Dengue virus (DENV) is caused by any of four closely related, but antigenically distinct and genetically diverse, virus serotypes (DENV-1, -2, -3, and -4), which are transmitted by day-biting, peridomestic Aedes mosquitoes, primarily Aedes aegypti (6). Incompletely understood immunological interactions among serotypes that can enhance disease severity (7-9) have hampered the development of effective, commercially available vaccines. A recent trial of a promising vaccine candidate demonstrated only partial (<33%) protection (10). Effective antiviral therapeutics are also not available. Thus, despite nearly a century of research, the only tools presently available to combat dengue target mosquito populations, mostly with insecticides and larval source reduction. In current practice, these tools are most often only partially effective (11). Although new vector control approaches are under development (12), innovations in dengue-control approaches are constrained by our limited understanding of virus-transmission dynamics and its drivers. In particular, the role of human movemen...

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Section: Discussionmentioning

confidence: 83%

House-to-house human movement drives dengue virus transmission

Stoddard

Forshey

Morrison

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

447

425

View full text Add to dashboard Cite

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“…PRNT results have been recognized to vary significantly depending on the conditions of the assay. 28 In our study, PRNT assays of all samples from each infant were conducted in the same run to minimize variability within infants. Analytical techniques were used to separate random variation from statistically significant differences.…”

Section: Discussionmentioning

confidence: 99%

Decay and Persistence of Maternal Dengue Antibodies among Infants in Bangkok

Panhuis

Luxemburger²,

Pengsaa

et al. 2011

The American Society of Tropical Medicine and Hygiene

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Maternal dengue antibodies are important in determining the optimal age of dengue vaccination, but no study has quantified the heterogeneity of antibody decay and persistence in infants. We used longitudinal regression methods and survival analysis to measure decay and persistence times of serotype-specific neutralizing antibodies in 139 infants in Bangkok. A biphasic decay pattern was found with half-life times of 24–29 days between birth and 3 months and 44–150 days after 3 months. Atypical decay rates were found in 17% of infants for dengue virus-1 and -4. Median persistence times of plaque reduction neutralization tests > 10 ranged from 6 to 9 months. Persistence times for individuals could not be predicted based on antibody values at birth. Vaccination against dengue before 12 months of age would be ineffective if maternal antibodies at plaque reduction neutralization test levels below 80 interfere with vaccine uptake. Projections of average antibody persistence based on values at birth should be avoided in studies on dengue pathogenesis in infants.

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“…This is an important consideration because variability has been shown in the DENV neutralization assay. 16 A 60% reduction in plaques at the initial 1:20 dilution qualified as a positive test result for a specific serotype. To discount possible confounding residual maternal antibody in the youngest children studied, minimal titers > 100 in 7-month-old children, > 50 in 8-month-old children, and > 25 in 9-month-old children were required to be counted as a primary infection.…”

Section: Methodsmentioning

confidence: 99%

Serologic Imprint of Dengue Virus in Urban Haiti: Characterization of Humoral Immunity to Dengue in Infants and Young Children

Rioth¹,

Beauharnais²,

Noël³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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Dengue is endemic to Haiti but not recognized as an important illness in the autochthonous population. To evaluate the prevalence of antibodies to dengue virus (DENV), serum samples from infants and young children 7–36 months of age (n = 166) were assayed by plaque reduction neutralization assays to each DENV serotype. Dengue virus serotype 1 had infected 40% of this study population, followed by serotype 2 (12%), serotype 3 (11%), and serotype 4 (2%). Fifty-three percent of infants and young children less than 12 months of age had already experienced DENV infection, and the seroprevalence of antibody to DENV increased to 65% by 36 months. Heterotypic antibody responses were an important component of the total dengue immunity profile.

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Dengue Plaque Reduction Neutralization Test (PRNT) in Primary and Secondary Dengue Virus Infections: How Alterations in Assay Conditions Impact Performance

Cited by 191 publications

References 34 publications

House-to-house human movement drives dengue virus transmission

House-to-house human movement drives dengue virus transmission

Decay and Persistence of Maternal Dengue Antibodies among Infants in Bangkok

Serologic Imprint of Dengue Virus in Urban Haiti: Characterization of Humoral Immunity to Dengue in Infants and Young Children

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