Invasive Meningococcal Disease at Fort Ord and San Diego Naval Training Center, 1962-1964.

Meningococcal epidemics at 2 training facilities were early examples of outbreaks fueled by military demographics and because of lethal drug-resistant bacteria for which there are no vaccines or chemoprophylaxis. Positive outcomes included the elucidation of the natural history of meningococcal colonization and disease and the initiation of vaccine development.

Treatment-focused Ebola trials, supportive care and future of filovirus care.

INTRODUCTION: During the 2014-2016 Ebolavirus (EBOV) outbreak, several candidate therapeutics were used in EBOV-infected patients in clinical trials and under expanded access for emergency use. This review will focus briefly on medications used during the outbreak. We will discuss current therapeutic candidates and their status and will then turn to a related and essential topic: supportive care and the standard of care for filovirus infected patients. Potential benefits and pitfalls of combination therapies for filoviruses will be discussed. Areas covered: Clinical trials of therapeutics targeting EBOV; clinical usage of therapeutics during recent EBOV outbreak; potential need for combination therapy; role of supportive care in treatment of Ebola virus disease (EVD). Expert commentary: In the absence of another large scale EBOV outbreak, the path to therapeutic product licensure in the United States of America (USA) would need to be via the FDA Animal Rule. However, human data may be needed to supplement animal data. The future of filovirus therapeutics may therefore benefit by establishing the ability to implement clinical trials in an outbreak setting in a timely fashion. Supportive care guidelines for filovirus infection should be defined and established as standard of care for treatment of EVD.

Ebola Virus Causes Intestinal Tract Architectural Disruption and Bacterial Invasion in Non-Human Primates.

In the 2014⁻2016 West Africa Ebola Virus (EBOV) outbreak, there was a significant concern raised about the potential for secondary bacterial infection originating from the gastrointestinal tract, which led to the empiric treatment of many patients with antibiotics. This retrospective pathology case series summarizes the gastrointestinal pathology observed in control animals in the rhesus EBOV-Kikwit intramuscular 1000 plaque forming unit infection model. All 31 Non-human primates (NHPs) exhibited lymphoid depletion of gut-associated lymphoid tissue (GALT) but the severity and the specific location of the depletion varied. Mesenteric lymphoid depletion and necrosis were present in 87% (27/31) of NHPs. There was mucosal barrier disruption of the intestinal tract with mucosal necrosis and/or ulceration most notably in the duodenum (16%), cecum (16%), and colon (29%). In the intestinal tract, hemorrhage was noted most frequently in the duodenum (52%) and colon (45%). There were focal areas of bacterial submucosal invasion in the gastrointestinal (GI) tract in 9/31 (29%) of NHPs. Only 2/31 (6%) had evidence of pancreatic necrosis. One NHP (3%) experienced jejunal intussusception which may have been directly related to EBOV. Immunofluorescence assays demonstrated EBOV antigen in CD68+ macrophage/monocytes and endothelial cells in areas of GI vascular injury or necrosis.

Designing a biocontainment unit to care for patients with serious communicable diseases: a consensus statement.

In spite of great advances in medicine, serious communicable diseases are a significant threat. Hospitals must be prepared to deal with patients who are infected with pathogens introduced by a bioterrorist act (e.g., smallpox), by a global emerging infectious disease (e.g., avian influenza, viral hemorrhagic fevers), or by a laboratory accident. One approach to hazardous infectious diseases in the hospital setting is a biocontainment patient care unit (BPCU). This article represents the consensus recommendations from a conference of civilian and military professionals involved in the various aspects of BPCUs. The role of these units in overall U.S. preparedness efforts is discussed. Technical issues, including medical care issues (e.g., diagnostic services, unit access); infection control issues (e.g., disinfection, personal protective equipment); facility design, structure, and construction features; and psychosocial and ethical issues, are summarized and addressed in detail in an appendix. The consensus recommendations are presented to standardize the planning, design, construction, and operation of BPCUs as one element of the U.S. preparedness effort.

History of U.S. military contributions to the study of bacterial zoonoses.

Bacterial zoonoses have afflicted campaigns throughout military history, at times playing an important role in determining their outcomes. In addition, zoonotic bacteria are among the leading biological warfare threats. The U.S. military medical services have been at the forefront of research to define the basic microbiology, ecology, epidemiology, and clinical aspects of these diseases. This historical review discusses the military significance of plague, Q fever, anthrax, leptospirosis, bartonellosis, tularemia, and brucellosis and the U.S. military medical research counteroffensive. These contributions have ranged from basic molecular biology to elegant epidemiological surveys, from defining pathogenesis to developing new vaccine candidates. In an era of emerging diseases and biological weapons, the U.S. military will continue to lead a dynamic research effort to counter these disease threats.

Evaluation of Signature Erosion in Ebola Virus Due to Genomic Drift and Its Impact on the Performance of Diagnostic Assays.

Genome sequence analyses of the 2014 Ebola Virus (EBOV) isolates revealed a potential problem with the diagnostic assays currently in use; i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. We evaluated signature erosion in ebolavirus molecular assays using an in silico approach and found frequent potential false-negative and false-positive results. We further empirically evaluated many EBOV assays, under real time PCR conditions using EBOV Kikwit (1995) and Makona (2014) RNA templates. These results revealed differences in performance between assays but were comparable between the old and new EBOV templates. Using a whole genome approach and a novel algorithm, termed BioVelocity, we identified new signatures that are unique to each of EBOV, Sudan virus (SUDV), and Reston virus (RESTV). Interestingly, many of the current assay signatures do not fall within these regions, indicating a potential drawback in the past assay design strategies. The new signatures identified in this study may be evaluated with real-time reverse transcription PCR (rRT-PCR) assay development and validation. In addition, we discuss regulatory implications and timely availability to impact a rapidly evolving outbreak using existing but perhaps less than optimal assays versus redesign these assays for addressing genomic changes.

Challenges, progress, and opportunities: proceedings of the filovirus medical countermeasures workshop.

On August 22-23, 2013, agencies within the United States Department of Defense (DoD) and the Department of Health and Human Services (HHS) sponsored the Filovirus Medical Countermeasures (MCMs) Workshop as an extension of the activities of the Filovirus Animal Non-clinical Group (FANG). The FANG is a federally-recognized multi-Agency group established in 2011 to coordinate and facilitate U.S. government (USG) efforts to develop filovirus MCMs. The workshop brought together government, academic and industry experts to consider the needs for filovirus MCMs and evaluate the status of the product development pipeline. This report summarizes speaker presentations and highlights progress and challenges remaining in the field.