Last data update: Jun 24, 2024. (Total: 47078 publications since 2009)
Records 1-4 (of 4 Records) |
Query Trace: Fanning M [original query] |
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Network analysis of the chronic Hepatitis C virome defines HVR1 evolutionary phenotypes in the context of humoral immune responses.
Palmer BA , Schmidt-Martin D , Dimitrova Z , Skums P , Crosbie O , Kenny-Walsh E , Fanning LJ . J Virol 2015 90 (7) 3318-29 Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) comprises the first 27 N-terminal amino acid residues of E2. It is classically seen as the most heterogeneous region of the HCV genome. In this study, we assessed HVR1 evolution by using ultradeep pyrosequencing for a cohort of treatment-naive, chronically infected patients over a short, 16-week period. Organization of the sequence set into connected components that represented single nucleotide substitution events revealed a network dominated by highly connected, centrally positioned master sequences. HVR1 phenotypes were observed to be under strong purifying (stationary) and strong positive (antigenic drift) selection pressures, which were coincident with advancing patient age and cirrhosis of the liver. It followed that stationary viromes were dominated by a single HVR1 variant surrounded by minor variants comprised from conservative single amino acid substitution events. We present evidence to suggest that neutralization antibody efficacy was diminished for stationary-virome HVR1 variants. Our results identify the HVR1 network structure during chronic infection as the preferential dominance of a single variant within a narrow sequence space. IMPORTANCE: HCV infection is often asymptomatic, and chronic infection is generally well established in advance of initial diagnosis and subsequent treatment. HVR1 can undergo rapid sequence evolution during acute infection, and the variant pool is typically seen to diverge away from ancestral sequences as infection progresses from the acute to the chronic phase. In this report, we describe HVR1 viromes in chronically infected patients that are defined by a dominant epitope located centrally within a narrow variant pool. Our findings suggest that weakened humoral immune activity, as a consequence of persistent chronic infection, allows for the acquisition and maintenance of host-specific adaptive mutations at HVR1 that reflect virus fitness. |
A mathematical model to estimate the state-specific impact of the Health Resources and Services Administration's Ryan White HIV/AIDS Program
Klein PW , Cohen SM , Uzun Jacobson E , Li Z , Clark G , Fanning M , Sterling R , Young SR , Sansom S , Hauck H . PLoS One 2020 15 (6) e0234652 BACKGROUND: Access to and engagement in high-quality HIV medical care and treatment is essential for ending the HIV epidemic. The Health Resources and Services Administration's (HRSA) Ryan White HIV/AIDS Program (RWHAP) plays a critical role in ensuring that people living with diagnosed HIV (PLWH) are linked to and consistently engaged in high quality care and receive HIV medication in a timely manner. State variation in HIV prevalence, the proportion of PLWH served by the RWHAP, and local health care environments could influence the state-specific impact of the RWHAP. This analysis sought to measure the state-specific impact of the RWHAP on the HIV service delivery system and health outcomes for PLWH, and presents template language to communicate this impact for state planning and stakeholder engagement. METHODS AND FINDINGS: The HRSA's HIV/AIDS Bureau (HAB) and the Centers for Disease Control and Prevention's Division of HIV/AIDS Prevention (CDC DHAP) have developed a mathematical model to estimate the state-specific impact of the RWHAP. This model was parameterized using RWHAP data, HIV surveillance data, an existing CDC model of HIV transmission and disease progression, and parameters from the literature. In this study, the model was used to analyze the hypothetical scenario of an absence of the RWHAP and to calculate the projected impact of this scenario on RWHAP clients, RWHAP-funded providers, mortality, new HIV cases, and costs compared with the current state inclusive of the RWHAP. To demonstrate the results of the model, we selected two states, representing high HIV prevalence and low HIV prevalence areas. These states serve to demonstrate the functionality of the model and how state-specific results can be translated into a state-specific impact statement using template language. CONCLUSIONS: In the example states presented, the RWHAP provides HIV care, treatment, and support services to a large proportion of PLWH in each state. The absence of the RWHAP in these states could result in substantially more deaths and HIV cases than currently observed, resulting in considerable lifetime HIV care and treatment costs associated with additional HIV cases. State-specific impact statements may be valuable in the development of state-level HIV prevention and care plans or for communications with planning bodies, state health department leadership, and other stakeholders. State-specific impact statements will be available to RWHAP Part B recipients upon request from HRSA's HIV/AIDS Bureau. |
Performance of point of dispensing setup drills for distribution of medical countermeasures: United States and Territories, 2012-2016
Pagaoa M , Leblanc TT , Renard P Jr , Brown S , Fanning M , Avchen RN . Am J Public Health 2018 108 S221-s223 OBJECTIVES: To describe results of points of dispensing (POD) medical countermeasure drill performance among local jurisdictions. METHODS: To compare POD setup times for each year, we calculated descriptive statistics of annual jurisdictional POD setup data submitted by over 400 local jurisdictions across 50 states and 8 US territories to a Centers for Disease Control and Prevention (CDC) program monitoring database from July 2012 to June 2016. RESULTS: In data collected from July 2012 to June 2015, fewer than 5% of PODs required more than 240 minutes to set up, although the proportion increased from July 2015 to June 2016 to almost 12%. From July 2012 to June 2016, more than 60% of PODs were set up in less than 90 minutes, with 60 minutes as the median setup time during the period. CONCLUSIONS: Our results yield evidence of national progress for response to a mass medical emergency. Technical assistance may be required to aid certain jurisdictions for improvement. Public Health Implications. The results of this study may inform future target times for performance on POD setup activities and highlight jurisdictions in need of technical assistance. |
Development and validation of a PulseNet standardized protocol for subtyping isolates of Cronobacter species
Brengi SP , O'Brien SB , Pichel M , Iversen C , Arduino M , Binsztein N , Jensen B , Pagotto F , Ribot EM , Stephan R , Cernela N , Cooper K , Fanning S . Foodborne Pathog Dis 2012 9 (9) 861-7 Cronobacter (formerly known as Enterobacter sakazakii) is a genus comprising seven species regarded as opportunistic pathogens that can be found in a wide variety of environments and foods, including powdered infant formula (PIF). Cronobacter sakazakii, the major species of this genus, has been epidemiologically linked to cases of bacteremia, meningitis in neonates, and necrotizing enterocolitis, and contaminated PIF has been identified as an important source of infection. Robust and reproducible subtyping methods are required to aid in the detection and investigation, of foodborne outbreaks. In this study, a pulsed-field gel electrophoresis (PFGE) protocol was developed and validated for subtyping Cronobacter species. It was derived from an existing modified PulseNet protocol, wherein XbaI and SpeI were the primary and secondary restriction enzymes used, generating an average of 14.7 and 20.3 bands, respectively. The PFGE method developed was both reproducible and discriminatory for subtyping Cronobacter species. |
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