Internet-based biosurveillance methods for vector-borne diseases: Are they novel public health tools or just novelties?

<div><p>Internet-based surveillance methods for vector-borne diseases (VBDs) using “big data” sources such as Google, Twitter, and internet newswire scraping have recently been developed, yet reviews on such “digital disease detection” methods have focused on respiratory pathogens, particularly in high-income regions. Here, we present a narrative review of the literature that has examined the performance of internet-based biosurveillance for diseases caused by vector-borne viruses, parasites, and other pathogens, including Zika, dengue, other arthropod-borne viruses, malaria, leishmaniasis, and Lyme disease across a range of settings, including low- and middle-income countries. The fundamental features, advantages, and drawbacks of each internet big data source are presented for those with varying familiarity of “digital epidemiology.” We conclude with some of the challenges and future directions in using internet-based biosurveillance for the surveillance and control of VBD.</p></div

Logistic fits of the observed dose-responses.

<p>The percentage of mosquitoes found virus-positive 7 days (<b>A</b>) and 14 days (<b>B</b>) after oral challenge is shown as a function of the blood meal titer for all combinations of two <i>Ae. aegypti</i> populations (NB =  Na Bo Kham; NC =  Nakhon Chum) and six DENV-2 virus isolates (experiment 1: isolates 29, 54, 66 and 67; experiment 2: isolates 50 and 51). Symbols represent empirical data and lines are logistic fits of the data. Solid symbols and lines correspond to the NB population; Open symbols and dashed lines represent the NC population. Note that the logistic fit of the 51-NB pair at day 14 was omitted from the figure because parameter estimates were unstable.</p

Multifactorial logistic regression of infection status.

<p>Significant <i>P</i>-values (<0.05) are in bold. df: degrees of freedom; L-R: likelihood ratio.</p

Genetic Characterization of Spondweni and Zika Viruses and Susceptibility of Geographically Distinct Strains of <i>Aedes aegypti</i>, <i>Aedes albopictus</i> and <i>Culex quinquefasciatus</i> (Diptera: Culicidae) to Spondweni Virus

<div><p>Background</p><p>Zika virus (ZIKV) has extended its known geographic distribution to the New World and is now responsible for severe clinical complications in a subset of patients. While substantial genetic and vector susceptibility data exist for ZIKV, less is known for the closest related flavivirus, Spondweni virus (SPONV). Both ZIKV and SPONV have been known to circulate in Africa since the mid-1900s, but neither has been genetically characterized by gene and compared in parallel. Furthermore, the susceptibility of peridomestic mosquito species incriminated or suspected in the transmission of ZIKV to SPONV was unknown.</p><p>Methodology/Principal Findings</p><p>In this study, two geographically distinct strains of SPONV were genetically characterized and compared to nine genetically and geographically distinct ZIKV strains. Additionally, the susceptibility of both SPONV strains was determined in three mosquito species. The open reading frame (ORF) of the SPONV 1952 Nigerian Chuku strain, exhibited a nucleotide and amino acid identity of 97.8% and 99.2%, respectively, when compared to the SPONV 1954 prototype South African SA Ar 94 strain. The ORF of the SPONV Chuku strain exhibited a nucleotide and amino acid identity that ranged from 68.3% to 69.0% and 74.6% to 75.0%, respectively, when compared to nine geographically and genetically distinct strains of ZIKV. The ORF of the nine African and Asian lineage ZIKV strains exhibited limited nucleotide divergence. <i>Aedes aegypti</i>, <i>Ae</i>. <i>albopictus</i> and <i>Culex quinquefasciatus</i> susceptibility and dissemination was low or non-existent following artificial infectious blood feeding of moderate doses of both SPONV strains.</p><p>Conclusions/Significance</p><p>SPONV and ZIKV nucleotide and amino acid divergence coupled with differences in geographic distribution, ecology and vector species support previous reports that these viruses are separate species. Furthermore, the low degree of SPONV infection or dissemination in <i>Ae</i>. <i>albopictus</i>, <i>Ae</i>. <i>aegypti</i> and <i>Cx</i>. <i>quinquefasciatus</i> following exposure to two geographically and genetically distinct virus strains suggest a low potential for these species to serve as vectors.</p></div

Immunogenic Properties of a BCG Adjuvanted Chitosan Nanoparticle-Based Dengue Vaccine in Human Dendritic Cells

<div><p>Dengue viruses (DENVs) are among the most rapidly and efficiently spreading arboviruses. WHO recently estimated that about half of the world’s population is now at risk for DENV infection. There is no specific treatment or vaccine available to treat or prevent DENV infections. Here, we report the development of a novel dengue nanovaccine (DNV) composed of UV-inactivated DENV-2 (UVI-DENV) and <i>Mycobacterium bovis</i> Bacillus Calmette-Guerin cell wall components (BCG-CWCs) loaded into chitosan nanoparticles (CS-NPs). CS-NPs were prepared by an emulsion polymerization method prior to loading of the BCG-CWCs and UVI-DENV components. Using a scanning electron microscope and a zetasizer, DNV was determined to be of spherical shape with a diameter of 372.0 ± 11.2 nm in average and cationic surface properties. The loading efficacies of BCG-CWCs and UVI-DENV into the CS-NPs and BCG-CS-NPs were up to 97.2 and 98.4%, respectively. THP-1 cellular uptake of UVI-DENV present in the DNV was higher than soluble UVI-DENV alone. DNV stimulation of immature dendritic cells (iDCs) resulted in a significantly higher expression of DCs maturation markers (CD80, CD86 and HLA-DR) and induction of various cytokine and chemokine productions than in UVI-DENV-treated iDCs, suggesting a potential use of BCG- CS-NPs as adjuvant and delivery system for dengue vaccines.</p></div

Reported geographic distribution of Spondweni virus^*.

<p>Reported geographic distribution of Spondweni virus^{<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0005083#t001fn001" target="_blank">*</a>}.</p

Evaluation of a Dengue NS1 Antigen Detection Assay Sensitivity and Specificity for the Diagnosis of Acute Dengue Virus Infection

<div><p>Background</p><p>Currently, no dengue NS1 detection kit has regulatory approval for the diagnosis of acute dengue fever. Here we report the sensitivity and specificity of the InBios DEN Detect NS1 ELISA using a panel of well characterized human acute fever serum specimens.</p><p>Methodology/Principal Findings</p><p>The InBios DENV Detect NS1 ELISA was tested using a panel composed of 334 serum specimens collected from acute febrile patients seeking care in a Bangkok hospital in 2010 and 2011. Of these patients, 314 were found to have acute dengue by either RT-PCR and/or anti-dengue IgM/IgG ELISA. Alongside the InBios NS1 ELISA kit, we compared the performance characteristics of the BioRad Platelia NS1 antigen kit. The InBios NS1 ELISA Ag kit had a higher overall sensitivity (86% vs 72.8%) but equal specificity (100%) compared to the BioRad Platelia kit. The serological status of the patient significantly influenced the outcome. In primary infections, the InBios NS1 kit demonstrated a higher sensitivity (98.8%) than in secondary infections (83.5%). We found significant variation in the sensitivity of the InBios NS1 ELISA kit depending on the serotype of the dengue virus and also found decreasing sensitivity the longer after the onset of illness, showing 100% sensitivity early during illness, but dropping below 50% by Day 7.</p><p>Conclusion/Significance</p><p>The InBios NS1 ELISA kit demonstrated high accuracy when compared to the initial clinical diagnosis with greater than 85% agreement when patients were clinically diagnosed with dengue illness. Results presented here suggest the accurate detection of circulating dengue NS1 by the InBios DENV Detect NS1 ELISA can provide clinicians with a useful tool for diagnosis of early dengue infections.</p></div

Genome structure and pairwise comparison of the open reading frame (ORF) of Spondweni (SPONV) and Zika (ZIKV) viruses.*

<p>A) SPONV genome organization: capsid (C), premembrane/membrane (prM), envelope (E), NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5. Numbers indicate animo acids in each protein. B) Pairwise comparison of the ORF of SPONV and ZIKV strains. SPONV SA Ar 94; SPONV Chuku; ZIKV MR 766; ZIKV ArB 13565; ZIKV ArD 41519; ZIKV P6-740; ZIKV CPC-0740; ZIKV EC Yap; ZIKV H/PF/2013; ZIKV Z1106033; ZIKV PRVABC59. *Boldface type (upper diagonal) = Percent amino acid identity; Lightface type (lower diagonal) = Percent nucleotide identity.</p

Identification of BCG-CWCs localization on BCG-CS-NPs observed with ConA induced aggregation.

<p>ConA solution was added into CS-NPs or BCG-CS-NPs to induce NPs aggregation whereas ConA+MDM was added as an inhibitor of ConA. Aggregation was measured by zetasizer at the designated time point starting from 0, 5, 10 and 20 minutes. * indicates a significant difference in particle sizeof BCG-CS-NPs in the presence or absence of ConA or ConA inhibitor. ** indicates a significant difference in particle size of CS-NPs in the presence or absence of ConA or ConA inhibitor. *** indicates a significant difference in particle size of BCG-CS-NPs and CS-NPs in the presence of ConA.</p

The presence of BCG-CWCs and UVI-DENV antigen in different NP preparations.

<p>NPs in each step of the DNV preparation were stained with anti-LAM (A) and anti-DENV (B) antibodies and the mean fluorescence intensity (MFI) were measured by flow cytometry.</p