Large-scale viral surveillance studies are critical to monitoring the global emergence of infectious disease and yield important information about the prevalence and seasonality of circulating virus species and the possible existence of novel species. Many large epidemiologic studies that have been conducted in temperate countries have not been repeated in tropical settings, however, and are likely to reveal viral burden and incidence variations due to inherent environmental and social differences. Dengue virus (DV) is an archetypal emerging infectious disease that infects an estimated 50-100 million people annually in a rapidly expanding geographic range and is the most common vector-borne viral disease of humans. Currently available lab diagnostic methods, however, fail to detect DV infection in 30-70% of patients presenting with hallmark dengue symptoms. The purpose of this study is twofold: to use the best available diagnostic technologies to delineate the spectrum of viral pathogens in a developing tropical environment with respect to dengue-like illnesses and to utilize the data provided by the extensive screening as a platform for the discovery of novel or divergent human viral pathogens. In collaboration with Eva Harris, this study will use the Virochip (UCSF) to characterize human sera and PBMC samples from Nicaraguan patients from the proposed hospital-based study presenting with dengue-like symptoms over multiple seasons. This will allow us to capture both the prevalence, seasonality and dual infection rates for all known viruses in suspected dengue cases over time. We also propose to utilize ultra-deep sequencing for a select number of samples based on several criteria including severity of symptoms for discovery of previously uncharacterized agents. We will pursue full genome cloning and molecular characterization for promising leads, including development of PCR-based rapid diagnostics and serological reagents for subsequent association studies.
Monitoring the threat of international emerging infectious disease requires proactive viral surveillance studies in tropical environments where many large epidemiologic studies have not been conducted. The convergence of viral diagnostic resources at UCSF and ongoing sample collection via the proposed hospital-based study in Nicaragua presents a rare opportunity to delineate the full spectrum of emerging and uncharacterized viral pathogens associated with pediatric dengue-like illness in a tropical setting using the most recently developed comprehensive molecular tools.
|Tsai, Wen-Yang; Youn, Han Ha; Tyson, Jasmine et al. (2018) Use of Urea Wash ELISA to Distinguish Zika and Dengue Virus Infections. Emerg Infect Dis 24:1355-1359|
|Thongsripong, Panpim; Chandler, James Angus; Green, Amy B et al. (2018) Mosquito vector-associated microbiota: Metabarcoding bacteria and eukaryotic symbionts across habitat types in Thailand endemic for dengue and other arthropod-borne diseases. Ecol Evol 8:1352-1368|
|Katzelnick, Leah C; Ben-Shachar, Rotem; Mercado, Juan Carlos et al. (2018) Dynamics and determinants of the force of infection of dengue virus from 1994 to 2015 in Managua, Nicaragua. Proc Natl Acad Sci U S A 115:10762-10767|
|Clemens, Daniel L; Lee, Bai-Yu; Horwitz, Marcus A (2018) The Francisella Type VI Secretion System. Front Cell Infect Microbiol 8:121|
|Huwyler, Camille; Heiniger, Nadja; Chomel, Bruno B et al. (2017) Dynamics of Co-Infection with Bartonella henselae Genotypes I and II in Naturally Infected Cats: Implications for Feline Vaccine Development. Microb Ecol 74:474-484|
|Norris, Michael H; Heacock-Kang, Yun; Zarzycki-Siek, Jan et al. (2017) Burkholderia pseudomallei natural competency and DNA catabolism: Identification and characterization of relevant genes from a constructed fosmid library. PLoS One 12:e0189018|
|Marques, Adriana R; Yang, Xiuli; Smith, Alexis A et al. (2017) Citrate Anticoagulant Improves the Sensitivity of Borreliella (Borrelia) burgdorferi Plasma Culture. J Clin Microbiol 55:3297-3299|
|Nualnoi, Teerapat; Norris, Michael H; Tuanyok, Apichai et al. (2017) Development of Immunoassays for Burkholderia pseudomallei Typical and Atypical Lipopolysaccharide Strain Typing. Am J Trop Med Hyg 96:358-367|
|Parameswaran, Poornima; Wang, Chunling; Trivedi, Surbhi Bharat et al. (2017) Intrahost Selection Pressures Drive Rapid Dengue Virus Microevolution in Acute Human Infections. Cell Host Microbe 22:400-410.e5|
|Bortell, Nikki; Flynn, Claudia; Conti, Bruno et al. (2017) Osteopontin Impacts West Nile virus Pathogenesis and Resistance by Regulating Inflammasome Components and Cell Death in the Central Nervous System at Early Time Points. Mediators Inflamm 2017:7582437|
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