Evaluation of Internet-Based Dengue Query Data: Google Dengue Trends

Dengue is a common and growing problem worldwide, with an estimated 70–140 million cases per year. Traditional, healthcare-based, government-implemented dengue surveillance is resource intensive and slow. As global Internet use has increased, novel, Internet-based disease monitoring tools have emerged. Google Dengue Trends (GDT) uses near real-time search query data to create an index of dengue incidence that is a linear proxy for traditional surveillance. Studies have shown that GDT correlates highly with dengue incidence in multiple countries on a large spatial scale. This study addresses the heterogeneity of GDT at smaller spatial scales, assessing its accuracy at the state-level in Mexico and identifying factors that are associated with its accuracy. We used Pearson correlation to estimate the association between GDT and traditional dengue surveillance data for Mexico at the national level and for 17 Mexican states. Nationally, GDT captured approximately 83% of the variability in reported cases over the 9 study years. The correlation between GDT and reported cases varied from state to state, capturing anywhere from 1% of the variability in Baja California to 88% in Chiapas, with higher accuracy in states with higher dengue average annual incidence. A model including annual average maximum temperature, precipitation, and their interaction accounted for 81% of the variability in GDT accuracy between states. This climate model was the best indicator of GDT accuracy, suggesting that GDT works best in areas with intense transmission, particularly where local climate is well suited for transmission. Internet accessibility (average ∼36%) did not appear to affect GDT accuracy. While GDT seems to be a less robust indicator of local transmission in areas of low incidence and unfavorable climate, it may indicate cases among travelers in those areas. Identifying the strengths and limitations of novel surveillance is critical for these types of data to be used to make public health decisions and forecasting models.     

The Ethnoecology of Dengue Fever

This article employs an ethnoecological analysis to link indigenous, ethnomedical, and Western biomedical ideas of infectious disease causation/ prevention. The ethnoecological analysis is expanded to include the cultural and historical context of political will and community participation in dengue fever control activities in an urban neighborhood in the Dominican Republic. Findings indicate that a key source of dengue fever transmission has been overlooked because it falls between established gender-role boundaries, and that mala union, an explanatory concept central to the failure of previous community-based interventions, emerges from local views of national political history. Data were generated through a neighborhood household survey, key respondent interviews, and participant-observation. [Ethnoecology, Caribbean, gender roles, dengue fever, Dominican Republic]     

Imported Dengue Cases,Weather Variation and Autochthonous Dengue Incidence in Cairns,Australia

Background

Dengue fever (DF) outbreaks often arise from imported DF cases in Cairns, Australia. Few studies have incorporated imported DF cases in the estimation of the relationship between weather variability and incidence of autochthonous DF. The study aimed to examine the impact of weather variability on autochthonous DF infection after accounting for imported DF cases and then to explore the possibility of developing an empirical forecast system.

Methodology/principal finds

Data on weather variables, notified DF cases (including those acquired locally and overseas), and population size in Cairns were supplied by the Australian Bureau of Meteorology, Queensland Health, and Australian Bureau of Statistics. A time-series negative-binomial hurdle model was used to assess the effects of imported DF cases and weather variability on autochthonous DF incidence. Our results showed that monthly autochthonous DF incidences were significantly associated with monthly imported DF cases (Relative Risk (RR):1.52; 95% confidence interval (CI): 1.01–2.28), monthly minimum temperature (^oC) (RR: 2.28; 95% CI: 1.77–2.93), monthly relative humidity (%) (RR: 1.21; 95% CI: 1.06–1.37), monthly rainfall (mm) (RR: 0.50; 95% CI: 0.31–0.81) and monthly standard deviation of daily relative humidity (%) (RR: 1.27; 95% CI: 1.08–1.50). In the zero hurdle component, the occurrence of monthly autochthonous DF cases was significantly associated with monthly minimum temperature (Odds Ratio (OR): 1.64; 95% CI: 1.01–2.67).

Conclusions/significance

Our research suggested that incidences of monthly autochthonous DF were strongly positively associated with monthly imported DF cases, local minimum temperature and inter-month relative humidity variability in Cairns. Moreover, DF outbreak in Cairns was driven by imported DF cases only under favourable seasons and weather conditions in the study.     

Oleic acid Enhances Dengue Virus But Not Dengue Virus-Like Particle Production from Mammalian Cells

Despite the recent introduction of a commercial vaccine, the mosquito-transmitted dengue virus is still a worldwide public health problem. Based on the live attenuated vaccine strategy, the commercial vaccine has a less than optimal protective profile. Virus-like particles (VLPs) offer an attractive alternate vaccination strategy due to the effectively native presentation of epitopes in the absence of any infectious genetic material. However, the production of amounts of VLP in a platform that can support commercial development remains a major obstacle. This study generated two DENV 2 VLPs [codon-optimized and chimeric DENV/Japanese encephalitis virus (JEV)] and directly compared yields of these constructs by western blotting and dot blot hybridization. The effect of oleic acid supplementation, a process known to increase DENV production in natural infection, was also investigated. Results showed that the chimeric construct gave a two- to threefold higher yield than the codon-optimized construct and that while oleic acid increased DENV virion production in natural infection, it inhibited VLP production. These results suggest that further optimization of DENV VLP expression is possible, but it will require more understanding of how native DENV infection remodels the host cell machinery.     

Evaluation of the Diagnostic Accuracy of a New Dengue IgA Capture Assay (Platelia Dengue IgA Capture,Bio-Rad) for Dengue Infection Detection

Considering the short lifetime of IgA antibodies in serum and the key advantages of antibody detection ELISAs in terms of sensitivity and specificity, Bio-Rad has just developed a new ELISA test based on the detection of specific anti-dengue IgA. This study has been carried out to assess the performance of this Platelia Dengue IgA Capture assay for dengue infection detection. A total of 184 well-characterized samples provided by the French Guiana NRC sera collection (Laboratory of Virology, Institut Pasteur in French Guiana) were selected among samples collected between 2002 and 2013 from patients exhibiting a dengue-like syndrome. A first group included 134 sera from confirmed dengue-infected patients, and a second included 50 sera from non-dengue infected patients, all collected between day 3 and day 15 after the onset of fever. Dengue infection diagnoses were all confirmed using reference assays by direct virological identification using RT-PCR or virus culture on acute sera samples or on paired acute-phase sera samples of selected convalescent sera. This study revealed: i) a good overall sensitivity and specificity of the IgA index test, i.e., 93% and 88% respectively, indicating its good correlation to acute dengue diagnosis; and ii) a good concordance with the Panbio IgM capture ELISA. Because of the shorter persistence of dengue virus-specific IgA than IgM, these results underlined the relevance of this new test, which could significantly improve dengue diagnosis accuracy, especially in countries where dengue virus is (hyper-) endemic. It would allow for additional refinement of dengue diagnostic strategy.     

First Experimental In Vivo Model of Enhanced Dengue Disease Severity through Maternally Acquired Heterotypic Dengue Antibodies

Dengue (DEN) represents the most serious arthropod-borne viral disease. DEN clinical manifestations range from mild febrile illness to life-threatening hemorrhage and vascular leakage. Early epidemiological observations reported that infants born to DEN-immune mothers were at greater risk to develop the severe forms of the disease upon infection with any serotype of dengue virus (DENV). From these observations emerged the hypothesis of antibody-dependent enhancement (ADE) of disease severity, whereby maternally acquired anti-DENV antibodies cross-react but fail to neutralize DENV particles, resulting in higher viremia that correlates with increased disease severity. Although in vitro and in vivo experimental set ups have indirectly supported the ADE hypothesis, direct experimental evidence has been missing. Furthermore, a recent epidemiological study has challenged the influence of maternal antibodies in disease outcome. Here we have developed a mouse model of ADE where DENV2 infection of young mice born to DENV1-immune mothers led to earlier death which correlated with higher viremia and increased vascular leakage compared to DENV2-infected mice born to dengue naïve mothers. In this ADE model we demonstrated the role of TNF-α in DEN-induced vascular leakage. Furthermore, upon infection with an attenuated DENV2 mutant strain, mice born to DENV1-immune mothers developed lethal disease accompanied by vascular leakage whereas infected mice born to dengue naïve mothers did no display any clinical manifestation. In vitro ELISA and ADE assays confirmed the cross-reactive and enhancing properties towards DENV2 of the serum from mice born to DENV1-immune mothers. Lastly, age-dependent susceptibility to disease enhancement was observed in mice born to DENV1-immune mothers, thus reproducing epidemiological observations.Overall, this work provides direct in vivo demonstration of the role of maternally acquired heterotypic dengue antibodies in the enhancement of dengue disease severity and offers a unique opportunity to further decipher the mechanisms involved.     

Symptomatic Dengue Disease in Five Southeast Asian Countries: Epidemiological Evidence from a Dengue Vaccine Trial

Dengue incidence has increased globally, but empirical burden estimates are scarce. Prospective methods are best-able to capture all severities of disease. CYD14 was an observer-blinded dengue vaccine study conducted in children 2–14 years of age in Indonesia, Malaysia, Thailand, the Philippines, and Vietnam. The control group received no vaccine and resembled a prospective, observational study. We calculated the rates of dengue according to different laboratory or clinical criteria to make inferences about dengue burden, and compared with rates reported in the passive surveillance systems to calculate expansion factors which describe under-reporting. Over 6,933 person-years of observation in the control group there were 319 virologically confirmed dengue cases, a crude attack rate of 4.6%/year. Of these, 92 cases (28.8%) were clinically diagnosed as dengue fever or dengue hemorrhagic fever by investigators and 227 were not, indicating that most symptomatic disease fails to satisfy existing case definitions. When examining different case definitions, there was an inverse relationship between clinical severity and observed incidence rates. CYD14’s active surveillance system captured a greater proportion of symptomatic dengue than national passive surveillance systems, giving rise to expansion factors ranging from 0.5 to 31.7. This analysis showed substantial, unpredictable and variable under-reporting of symptomatic dengue, even within a controlled clinical trial environment, and emphasizes that burden estimates are highly sensitive to case definitions. These data will assist in generating disease burden estimates and have important policy implications when considering the introduction and health economics of dengue prevention and control interventions.