Faculty Bibliography

OBJECTIVE:Healthcare personnel (HCP) were recruited to provide serum samples, which were tested for antibodies against Ebola or Lassa virus to evaluate for asymptomatic seroconversion. SETTING/METHODS:From 2014 to 2016, 4 patients with Ebola virus disease (EVD) and 1 patient with Lassa fever (LF) were treated in the Serious Communicable Diseases Unit (SCDU) at Emory University Hospital. Strict infection control and clinical biosafety practices were implemented to prevent nosocomial transmission of EVD or LF to HCP. PARTICIPANTS/METHODS:All personnel who entered the SCDU who were required to measure their temperatures and complete a symptom questionnaire twice daily were eligible. RESULTS:No employee developed symptomatic EVD or LF. EVD and LF antibody studies were performed on sera samples from 42 HCP. The 6 participants who had received investigational vaccination with a chimpanzee adenovirus type 3 vectored Ebola glycoprotein vaccine had high antibody titers to Ebola glycoprotein, but none had a response to Ebola nucleoprotein or VP40, or a response to LF antigens. CONCLUSIONS:Patients infected with filoviruses and arenaviruses can be managed successfully without causing occupation-related symptomatic or asymptomatic infections. Meticulous attention to infection control and clinical biosafety practices by highly motivated, trained staff is critical to the safe care of patients with an infection from a special pathogen.

Crimean-Congo hemorrhagic fever is the most geographically widespread tick-borne virus, with infection resulting in mortality in up to 30% of cases. Clinical diagnosis alone is difficult due to the nonspecific nature of symptoms; therefore, laboratory diagnostics should be utilized for patients with residence in or travel to regions of endemicity in whom the disease is suspected. This minireview provides an overview of laboratory tests available for Crimean-Congo hemorrhagic fever (CCHF) and their utility in diagnosis with a focus on diagnosing CCHF in humans.

During the 2014-16 W. Africa outbreak of Ebola virus disease, the US had no mechanism to study investigational treatments rapidly, and individual institutions provided investigational products as emergency investigational new drugs (eINDs). Consequently, determining the optimum care for the disease was not achieved. The Special Pathogens Research Network (SPRN) was established to create the infrastructure to conduct multi-center clinical research to improve outcomes for emerging special pathogens. This included establishing a central IRB at the University of Nebraska Medical Center and 10 collaborative sites across the US. As the COVID-19 outbreak began, the SPRN quickly executed three protocols. We share efficiencies and ideas for future improvements. At the onset of the COVID-19 outbreak, the network established three clinical protocols: 1) a "natural history" protocol for collecting discarded specimens and patient data; 2) a NIAID-sponsored randomized placebo controlled trial with the antiviral drug Remdesivir; and 3) a prospective data and sample collection protocol. We evaluated the IRB approval timeline centrally and at partner sites and the rapidity of first subject enrollment. We assessed aspects that facilitated or hindered the adoption of the different protocols across the network. Central and other site IRB approvals occurred expeditiously. Subjects were enrolled within one day of site approval in all three studies. UNMC enrolled the first US patient in the Remdesivir RCT. IRB approval occurred at all 10 sites within 32 days of central IRB approval; however, contracts for data use and material transfer agreements (DUAs and MTAs) lagged. Consequently, some sites developed their own natural history protocols, rather than adopt a network protocol. In conclusion, the SPRN pre-existing network of 10 sites was able to enroll subjects rapidly at the start of the outbreak, functioning as one unit in many respects. Contracting for specimen collection protocols has proved challenging and thus has impacted the ability to organize and deliver. This continues to be addressed

The human immune response to eastern equine encephalitis virus (EEEV) infection is poorly characterized due to the rarity of infection. We examined the humoral and cellular immune response to EEEV acquired from an infected donor via liver transplantation. Both binding and highly neutralizing antibodies to EEEV as well as a robust EEEV-specific IgG memory B cell response were generated. Despite triple-drug immunosuppressive therapy, a virus-specific CD4+ T cell response, predominated by interferon-γ production, was generated. T cell epitopes on the E2 envelope protein were identified by interferon-γ ELISpot. Although these results are from a single person who acquired EEEV by a non-traditional mechanism, to our knowledge this work represents the first analysis of the human cellular immune response to EEEV.

During the 2014-2016 Ebola virus disease (EVD) outbreak, clinicians lacked a readily available resource cataloguing available medical countermeasures (MCMs) to treat EVD patients in West Africa and other regions. Some patients received investigational interventions under uncontrolled compassionate use protocols. Therefore, the Special Pathogens Research Network (SPRN) of the National Ebola Training and Education Center (NETEC) formed the MCMs Working Group (WG) with members from 10 Regional Ebola and other Special Pathogen Treatment Centers (RESPTC) and NETEC partners. The goal of the MCMs WG is to develop an evidence-informed, easily accessible, practical assessment of potential countermeasures for clinicians managing patients with selected highly hazardous communicable diseases. Pathogens were selected based on 1) ability to cause severe disease; 2) potential to cause large outbreaks; 3) paucity of currently available cleared MCMs; 4) occurrence of nosocomial spread to health care providers; and 5) transmissibility requiring specialized care in a biocontainment unit. After a standardized literature review is conducted, an assessment of potentially available countermeasures is performed by 2-4 subject matter experts, followed by peer review. Pathogens selected to date incluDe Marburg, Lassa, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), Crimean Congo Hemorrhagic Fever (CCHF), Nipah, Variola (and Monkeypox) and South American Hemorrhagic Fever (Junin, Machupo, etc.) viruses. The list overlaps with the World Health Organization's list of ?Blueprint? priority diseases. Reviews on seven pathogens are in progress. In conclusion, the NETEC SPRN MCM WG was created to proviDe a preemptive compendium of systematic and clinically relevant summaries of available MCMs for selected pathogens based on pre-specified criteria. Challenges will incluDe updating current documents as new scientific evidence becomes available. Plans are in place for regular review and updates, with the most up-todate materials available on the NETEC website for open-source access