Jeffrey R. Miller

Bio: Jeffrey R. Miller is an academic researcher from Centers for Disease Control and Prevention. The author has contributed to research in topics: Outbreak & Case fatality rate. The author has an hindex of 6, co-authored 6 publications receiving 181 citations. Previous affiliations of Jeffrey R. Miller include Pennsylvania Department of Health.

Outbreak of influenza A (H3N2) variant virus infection among attendees of an agricultural fair, Pennsylvania, USA, 2011.

Abstract: During August 2011, influenza A (H3N2) variant [A(H3N2)v] virus infection developed in a child who attended an agricultural fair in Pennsylvania, USA; the virus resulted from reassortment of a swine influenza virus with influenza A(H1N1)pdm09. We interviewed fair attendees and conducted a retrospective cohort study among members of an agricultural club who attended the fair. Probable and confirmed cases of A(H3N2)v virus infection were defined by serology and genomic sequencing results, respectively. We identified 82 suspected, 4 probable, and 3 confirmed case-patients who attended the fair. Among 127 cohort study members, the risk for suspected case status increased as swine exposure increased from none (4%; referent) to visiting swine exhibits (8%; relative risk 2.1; 95% CI 0.2–53.4) to touching swine (16%; relative risk 4.4; 95% CI 0.8–116.3). Fairs may be venues for zoonotic transmission of viruses with epidemic potential; thus, health officials should investigate respiratory illness outbreaks associated with agricultural events.

Invasive Nontuberculous Mycobacterial Infections among Cardiothoracic Surgical Patients Exposed to Heater-Cooler Devices1.

Abstract: Invasive nontuberculous mycobacteria (NTM) infections may result from a previously unrecognized source of transmission, heater-cooler devices (HCDs) used during cardiac surgery. In July 2015, the Pennsylvania Department of Health notified the Centers for Disease Control and Prevention (CDC) about a cluster of NTM infections among cardiothoracic surgical patients at 1 hospital. We conducted a case-control study to identify exposures causing infection, examining 11 case-patients and 48 control-patients. Eight (73%) case-patients had a clinical specimen identified as Mycobacterium avium complex (MAC). HCD exposure was associated with increased odds of invasive NTM infection; laboratory testing identified patient isolates and HCD samples as closely related strains of M. chimaera, a MAC species. This investigation confirmed a large US outbreak of invasive MAC infections in a previously unaffected patient population and suggested transmission occurred by aerosolization from HCDs. Recommendations have been issued for enhanced surveillance to identify potential infections associated with HCDs and measures to mitigate transmission risk.

Multistate Outbreak of Burkholderia cepacia Complex Bloodstream Infections After Exposure to Contaminated Saline Flush Syringes: United States, 2016–2017

Abstract: Background Burkholderia cepacia complex (Bcc) has caused healthcare-associated outbreaks, often in association with contaminated products. The identification of 4 Bcc bloodstream infections in patients residing at a single skilled nursing facility (SNF) within 1 week led to an epidemiological investigation to identify additional cases and the outbreak source. Methods A case was initially defined via a blood culture yielding Bcc in a SNF resident receiving intravenous therapy after 1 August 2016. Multistate notifications were issued to identify additional cases. Public health authorities performed site visits at facilities with cases to conduct chart reviews and identify possible sources. Pulsed-field gel electrophoresis (PFGE) was performed on isolates from cases and suspect products. Facilities involved in manufacturing suspect products were inspected to assess possible root causes. Results An outbreak of 162 Bcc bloodstream infections across 59 nursing facilities in 5 states occurred during September 2016-January 2017. Isolates from patients and pre-filled saline flush syringes were closely related by PFGE, identifying contaminated flushes as the outbreak source and prompting a nationwide recall. Inspections of facilities at the saline flush manufacturer identified deficiencies that might have led to the failure to sterilize a specific case containing a partial lot of the product. Conclusions Communication and coordination among key stakeholders, including healthcare facilities, public health authorities, and state and federal agencies, led to the rapid identification of an outbreak source and likely prevented many additional infections. Effective processes to ensure the sterilization of injectable products are essential to prevent similar outbreaks in the future.

Community Mitigation Guidelines to Prevent Pandemic Influenza - United States, 2017.

Abstract: When a novel influenza A virus with pandemic potential emerges, nonpharmaceutical interventions (NPIs) often are the most readily available interventions to help slow transmission of the virus in communities, which is especially important before a pandemic vaccine becomes widely available. NPIs, also known as community mitigation measures, are actions that persons and communities can take to help slow the spread of respiratory virus infections, including seasonal and pandemic influenza viruses.These guidelines replace the 2007 Interim Pre-pandemic Planning Guidance: Community Strategy for Pandemic Influenza Mitigation in the United States - Early, Targeted, Layered Use of Nonpharmaceutical Interventions (https://stacks.cdc.gov/view/cdc/11425). Several elements remain unchanged from the 2007 guidance, which described recommended NPIs and the supporting rationale and key concepts for the use of these interventions during influenza pandemics. NPIs can be phased in, or layered, on the basis of pandemic severity and local transmission patterns over time. Categories of NPIs include personal protective measures for everyday use (e.g., voluntary home isolation of ill persons, respiratory etiquette, and hand hygiene); personal protective measures reserved for influenza pandemics (e.g., voluntary home quarantine of exposed household members and use of face masks in community settings when ill); community measures aimed at increasing social distancing (e.g., school closures and dismissals, social distancing in workplaces, and postponing or cancelling mass gatherings); and environmental measures (e.g., routine cleaning of frequently touched surfaces).Several new elements have been incorporated into the 2017 guidelines. First, to support updated recommendations on the use of NPIs, the latest scientific evidence available since the influenza A (H1N1)pdm09 pandemic has been added. Second, a summary of lessons learned from the 2009 H1N1 pandemic response is presented to underscore the importance of broad and flexible prepandemic planning. Third, a new section on community engagement has been included to highlight that the timely and effective use of NPIs depends on community acceptance and active participation. Fourth, to provide new or updated pandemic assessment and planning tools, the novel influenza virus pandemic intervals tool, the Influenza Risk Assessment Tool, the Pandemic Severity Assessment Framework, and a set of prepandemic planning scenarios are described. Finally, to facilitate implementation of the updated guidelines and to assist states and localities with prepandemic planning and decision-making, this report links to six supplemental prepandemic NPI planning guides for different community settings that are available online (https://www.cdc.gov/nonpharmaceutical-interventions).

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

Abstract: Background. Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. Methods. We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination. Results. We showed that YF-17D–induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D–neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination. Conclusion. Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity. Trial registration. Registration is not required for observational studies. Funding. This study was funded by Canada’s Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation, and United States Agency for International Development.

Outbreak of Variant Influenza A(H3N2) Virus in the United States

Abstract: Background Variant influenza virus infections are rare but may have pandemic potential if person-to-person transmission is efficient. We describe the epidemiology of a multistate outbreak of an influenza A(H3N2) variant virus (H3N2v) first identified in 2011. Methods We identified laboratory-confirmed cases of H3N2v and used a standard case report form to characterize illness and exposures. We considered illness to result from person-to-person H3N2v transmission if swine contact was not identified within 4 days prior to illness onset. Results From 9 July to 7 September 2012, we identified 306 cases of H3N2v in 10 states. The median age of all patients was 7 years. Commonly reported signs and symptoms included fever (98%), cough (85%), and fatigue (83%). Sixteen patients (5.2%) were hospitalized, and 1 fatal case was identified. The majority of those infected reported agricultural fair attendance (93%) and/or contact with swine (95%) prior to illness. We identified 15 cases of possible person-to-person transmission of H3N2v. Viruses recovered from patients were 93%-100% identical and similar to viruses recovered from previous cases of H3N2v. All H3N2v viruses examined were susceptible to oseltamivir and zanamivir and resistant to adamantane antiviral medications. Conclusions In a large outbreak of variant influenza, the majority of infected persons reported exposures, suggesting that swine contact at an agricultural fair was a risk for H3N2v infection. We identified limited person-to-person H3N2v virus transmission, but found no evidence of efficient or sustained person-to-person transmission. Fair managers and attendees should be aware of the risk of swine-to-human transmission of influenza viruses in these settings.

Molecular Epidemiology and Evolution of Influenza Viruses Circulating within European Swine between 2009 and 2013

Abstract: The emergence in humans of the A(H1N1)pdm09 influenza virus, a complex reassortant virus of swine origin, highlighted the importance of worldwide influenza virus surveillance in swine. To date, large-scale surveillance studies have been reported for southern China and North America, but such data have not yet been described for Europe. We report the first large-scale genomic characterization of 290 swine influenza viruses collected from 14 European countries between 2009 and 2013. A total of 23 distinct genotypes were identified, with the 7 most common comprising 82% of the incidence. Contrasting epidemiological dynamics were observed for two of these genotypes, H1huN2 and H3N2, with the former showing multiple long-lived geographically isolated lineages, while the latter had short-lived geographically diffuse lineages. At least 32 human-swine transmission events have resulted in A(H1N1)pdm09 becoming established at a mean frequency of 8% across European countries. Notably, swine in the United Kingdom have largely had a replacement of the endemic Eurasian avian virus-like (“avian-like”) genotypes with A(H1N1)pdm09-derived genotypes. The high number of reassortant genotypes observed in European swine, combined with the identification of a genotype similar to the A(H3N2)v genotype in North America, underlines the importance of continued swine surveillance in Europe for the purposes of maintaining public health. This report further reveals that the emergences and drivers of virus evolution in swine differ at the global level. IMPORTANCE The influenza A(H1N1)pdm09 virus contains a reassortant genome with segments derived from separate virus lineages that evolved in different regions of the world. In particular, its neuraminidase and matrix segments were derived from the Eurasian avian virus-like (“avian-like”) lineage that emerged in European swine in the 1970s. However, while large-scale genomic characterization of swine has been reported for southern China and North America, no equivalent study has yet been reported for Europe. Surveillance of swine herds across Europe between 2009 and 2013 revealed that the A(H1N1)pdm09 virus is established in European swine, increasing the number of circulating lineages in the region and increasing the possibility of the emergence of a genotype with human pandemic potential. It also has implications for veterinary health, making prevention through vaccination more challenging. The identification of a genotype similar to the A(H3N2)v genotype, causing zoonoses at North American agricultural fairs, underlines the importance of continued genomic characterization in European swine.