A Tale of Two Viruses: HPV Infection and Associated Anal Dysplasia among Hawai‘i HIV-Seropositive Patients and Related HIV-Seroconversion Risk in a Thai Population.

Ph.D. Thesis. University of Hawaiʻi at Mānoa 2017

Development of a thermostable, multivalent filovirus vaccine based on recombinant subunit proteins

Ebola Virus Disease (EVD) is the most prominent example of filovirus disease but despite being characterized as a Category A Priority Pathogen by NIH/NIAID over a decade ago, it lacked public and private research resources due to the absence of a commercial market. Transmission from wild animals into the human population typically causes outbreaks of limited scale in endemic areas located in the forested regions of Central Africa and the Philippines (for Reston ebolavirus). In the past decade, a Zaire Ebolavirus (EBOV) outbreak causing more than 11,000 deaths in several West African countries started to reveal the true epidemic potential that filovirus infections can have when entering an urban setting in a highly mobile society. In addition a persistent outbreak in the Democratic Republic of the Congo has continued since August 2018 despite significant progress with the clinical development of several EBOV vaccine candidates (one of which recently gained regulatory approvals in Europe, the U.S. and several African countries) and the advanced testing of promising EBOV specific therapeutics. Despite this significant progress, additional research is needed in particular on understanding the mechanism of protection and defining immune correlates of protection for Ebola and other filoviruses do develop fast and efficacious strategies for outbreak control as the incidence of outbreaks and total case numbers has significantly increased over the last decadesPlease click Download on the upper right corner to see the full abstract

Human Papillomavirus-16 DNA Quantitation Differentiates High-Grade Anal Neoplasia

Background: Due to their higher rates of anal dysplasia/cancer, human immunodeficiency virus (HIV)-positive individuals are recommended to undergo anal dysplasia screening, which consists of anal cytology (AC) and high resolution anoscopy (HRA) with anal biopsy (AB) after abnormal AC result. However, AC variability limits its usefulness. Our objective was to evaluate human papillomavirus (HPV)-16 DNA quantitation as part of the screening algorithm. Methods: HPV-16 was detected in AC specimens from 75 HIV-positive participants using quantitative real-time polymerase chain reaction. AB results were available from 18/44 patients who had abnormal AC. Statistical tests included Mann-Whitney U, Kruskal-Wallis, receiver operating characteristic (ROC) analysis and Kappa coefficient tests. Results: HPV-16 copy numbers differed significantly across AC (p = 0.001) and AB grades (p = 0.009). HPV-16 ≥ 65 copies/cell predicted high-grade AB (p = 0.04). Using this cut-off in comparison to AB, it had better specificity (1.00) than AC (0.75) and specificity (0.77) than qualitative HPV-16 detection (0.38). Also, the Kappa coefficient of the cut-off (κ = 0.649) was higher than AC (κ = 0.557) and qualitative HPV-16 detection (κ = 0.258) to AB. Conclusion: Higher HPV-16 copy numbers corresponded to higher AC and AB grades, suggesting the importance of HPV burden on disease stage. Furthermore, HPV-16 ≥ 65 copies/cell distinguished high-grade disease and demonstrated better sensitivity, specificity, and agreement with AB than AC or qualitative HPV-16 detection. These results support the potential use of HPV quantitation in conjunction with AC in anal dysplasia screening