Incomplete Protection against Dengue Virus Type 2 Re-infection in Peru

© 2016 Public Library of Science. All Rights Reserved. Background: Nearly half of the world’s population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010–2011, 15 years after the first outbreak of DENV-2 in the region. Methodology/Principal Findings: We estimated the age-dependent prevalence of serotype-specific DENV antibodies from longitudinal cohort studies conducted between 1993 and 2010. During the 2010–2011 epidemic, active dengue cases were identified through active community- and clinic-based febrile surveillance studies, and acute inapparent DENV infections were identified through contact tracing studies. Based on the age-specific prevalence of DENV-2 neutralizing antibodies, the age distribution of DENV-2 cases was markedly older than expected. Homologous protection was estimated at 35.1% (95% confidence interval: 0%–65.2%). At the individual level, pre-existing DENV-2 antibodies were associated with an incomplete reduction in the frequency of symptoms. Among dengue cases, 43% (26/66) exhibited elevated DENV-2 neutralizing antibody titers for years prior to infection, compared with 76% (13/17) of inapparent infections (age-adjusted odds ratio: 4.2; 95% confidence interval: 1.1–17.7). Conclusions/Significance: Our data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials. Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics

Alternative Tissue Sampling for Improved Detection of Candidatus Liberibacter asiaticus.

Early detection and prompt response are key factors in the eradication of huanglongbing (HLB) in California. Currently, qPCR testing of leaf tissue guides the removal of infected trees. However, because of the uneven distribution of Candidatus Liberibacter asiaticus (CLas) in an infected tree and asymptomatic infection, selecting the best leaves to sample, from a mature tree with more than 200,000 estimated leaves, is a major hurdle for timely detection. The goal of this study was to address this issue by testing alternative tissues that might improve the CLas detection rate. Using two years of field data, old and young leaves, peduncle bark of fruit, and feeder roots were evaluated for the presence of CLas. Quadrant-peduncle (Q-P) tissue sampling consistently resulted in better CLas detection than any other tissue type. Q-P samples had a 30% higher qPCR positivity rate than quadrant-leaf (Q-L) samples. No significant seasonal patterns were observed. Roots and single peduncles had similar detection rates; both were higher than single leaves or Q-L samples. If symptoms were used to guide sampling, 30% of infected trees would have been missed. Taken together, these results suggest that Q-P tissue sampling is the optimal choice for improved CLas detection under California growing conditions

Using models to provide rapid programme support for California's efforts to suppress Huanglongbing disease of citrus

We describe a series of operational questions posed during the state-wide response in California to the arrival of the invasive citrus disease Huanglongbing. The response is coordinated by an elected committee from the citrus industry and operates in collaboration with the California Department of Food and Agriculture, which gives it regulatory authority to enforce the removal of infected trees. The paper reviews how surveillance for disease and resource allocation between detection and delimitation have been addressed, based on epidemiological principles. In addition, we describe how epidemiological analyses have been used to support rule-making to enact costly but beneficial regulations and we highlight two recurring themes in the programme support work: (i) data are often insufficient for quantitative analyses of questions and (ii) modellers and decision-makers alike may be forced to accept the need to make decisions on the basis of simple or incomplete analyses that are subject to considerable uncertainty. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'. This theme issue is linked with the earlier issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'

Incomplete Protection against Dengue Virus Type 2 Re-infection in Peru.

BackgroundNearly half of the world's population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010-2011, 15 years after the first outbreak of DENV-2 in the region.Methodology/principal findingsWe estimated the age-dependent prevalence of serotype-specific DENV antibodies from longitudinal cohort studies conducted between 1993 and 2010. During the 2010-2011 epidemic, active dengue cases were identified through active community- and clinic-based febrile surveillance studies, and acute inapparent DENV infections were identified through contact tracing studies. Based on the age-specific prevalence of DENV-2 neutralizing antibodies, the age distribution of DENV-2 cases was markedly older than expected. Homologous protection was estimated at 35.1% (95% confidence interval: 0%-65.2%). At the individual level, pre-existing DENV-2 antibodies were associated with an incomplete reduction in the frequency of symptoms. Among dengue cases, 43% (26/66) exhibited elevated DENV-2 neutralizing antibody titers for years prior to infection, compared with 76% (13/17) of inapparent infections (age-adjusted odds ratio: 4.2; 95% confidence interval: 1.1-17.7).Conclusions/significanceOur data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials. Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics

Expected versus observed DENV-2 and DENV-4 cases.

<p>The observed age distribution of cases of DENV-2 (dark green in panels A, C, and D) and DENV-4 (dark purple in panel B). Using the ages of all febrile individuals that participated in a clinic-based febrile surveillance study[<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004398#pntd.0004398.ref017" target="_blank">17</a>], we built an empirical estimate of the age distribution of individuals who sought treatment in Iquitos. By multiplying this distribution by the age-specific percent of the population with serotype-specific dengue antibodies, we created serotype-specific expected age distributions of cases for DENV-2 and DENV-4 (light green in panel A and light purple in panel B). We then adjusted the age- and serotype-specific immune levels and recalculated expected age distributions of cases for DENV-2 by assuming, across all ages, either 25% or 50% of those who should have been immune were still susceptible to DENV-2 (light green in panel C and light green in panel D, respectively).</p

DENV-1 and DENV-2 neutralizing antibody prevalence by year and birth cohort.

<p>Samples were collected from longitudinal cohort studies conducted in Iquitos between 1993 and 2010. Panel A: DENV-1 neutralizing antibody prevalence by year, based on birth cohorts. Panel B: DENV-2 neutralizing antibody prevalence by year, based on birth cohorts.</p

Pre-epidemic DENV-2 neutralizing antibody prevalence among symptomatic and inapparent DENV-2 infections.

<p>Pre-epidemic DENV-2 neutralizing antibody prevalence among symptomatic and inapparent DENV-2 infections.</p

Pre-epidemic DENV-2 neutralizing antibody profiles of participants with subsequent confirmed DENV-2 infection in 2010–2011.

<p>Seroprevalence is based on a cutoff titer of 60. Geometric mean titers (GMT) are based on samples with detectable titers.</p

Neutralization of Am-DENV-2 and AA-DENV-2 test viruses using human serum from longitudinal cohort studies.

<p>Geometric mean titers (GMTs) for the individual test viruses and the average of the two GMTs are shown.</p