What SPB Does

Researcher in the BSL-4 Lab

The Special Pathogens Branch's (SPB) charter is the study of highly infectious viruses that also produce severe disease in humans. Our daily work involves the investigation of viruses that cause several hemorrhagic fevers, such as Ebola hemorrhagic fever, Lassa fever, and hantavirus pulmonary syndrome, and other recently identified and emerging viral diseases, such as Nipah virus encephalitis.

All of the infectious agents the branch works with are viruses. Each is RNA-coded (often negative-stranded or ambisense in coding strategy), encased in a lipid envelope, and displays some degree of aerosol infectivity in the laboratory. In addition, all of the viruses are vector-borne zoonotic agents (meaning that under normal conditions, these viruses exist in animals); the majority are found in rodents, but some occur in other mammals or arthropods as well.

All of these viruses are classified as Biosafety Level 4 (BSL-4) pathogens and as such must be handled in special facilities designed to contain them safely. For this reason, SPB operates one of the world's few BSL-4 laboratories.

Viruses causing hemorrhagic fever exist in many distant places around the globe, but today’s travel patterns can bring any one of them to the United States in a matter of hours. New or previously unidentified viruses continue to appear in countries throughout the world. We do not know how many agents eventually may be added to the list of those we study, but all of the following were discovered during the 1990s: Sabia virus, Guanarito virus, and Sin Nombre virus and other hantaviruses in the Americas; the Ivory Coast species of Ebola virus; the tick-borne flaviviruses in the Middle East; and Nipah virus in Southeast Asia.

Work Priorities

We have four related priorities in working with these viral agents:

• managing patients infected or suspected of being infected with these viruses
• developing diagnostic tools for rapidly and accurately identifying these viruses
• gathering information about theses viruses and diseases and their geographic distribution
• conducting studies to increase our basic scientific knowledge of these viruses, so we can predict their behavior and protect people from them more effectively.

At any moment, the work of SPB is prioritized as shown above. However, if our branch is to do its job in the broad sense, there must be a mix of all four objectives in the intermediate and long-term time frames. Relatively little is known about most of these diseases and their causative viruses. Each outbreak or endemic situation not only requires control measures, but also demands a measure of research so we can better prevent or respond to outbreaks in the future.

SPB uses the following concepts and tools to understand and control these diseases: public health practices, molecular biology, diagnostics, clinical medicine, epidemiology, immunology, pathogenesis, comparative biology, ecology, and community education. The Infectious Disease Pathology Activity (IDPA) at CDC assists SPB with diagnostic pathology and surveillance.

Key Challenges for SPB

Rift Valley fever virus electron micrograph

As noted previously, the number of known disease-causing viruses has been increasing. This trend is very likely to continue. We anticipate the recognition of new pathogenic arenaviruses, certainly from the Americas and probably from Africa. Hantavirus pulmonary syndrome is a widespread if uncommon problem in the Americas. In addition, new foci of disease and more viruses await discovery and exploration.

The behavior of the known viruses is also unlikely to remain static. They continue to appear in places and in epidemiologic contexts that are unpredictable and novel for us. Recent examples include the extensive stockyard disease seen with Crimean-Congo hemorrhagic fever in the Middle East; the appearance of the Reston species of Ebola virus in monkeys, as expected, but in an unexpected part of the world (Texas); the explosive outbreak of hantavirus pulmonary syndrome in Chile; and the first recorded outbreak of Rift Valley fever on the Arabian Peninsula.

Virus Transmission

Transmission of the viruses that cause these diseases continues to spark debate and research. As mentioned, the viruses we study display some capability of infection through small-particle aerosols in the laboratory. However, the role of aerosols in the transmission of these viruses (which happens primarily when people breathe in the aerosols) continues to raise some uncertainties.

While the aerosol route from the animal vectors to humans is well documented and is probably the dominant mode of transmission, some of these viruses can be transmitted person to person, usually through direct contact or nosocomial routes. Transmission of this nature is inefficient. However, some outbreaks of disease caused by these viruses can be best explained in terms of aerosol spread between persons. Such outbreaks often seem to be associated with a single patient who is the source for a number of secondary infections.

Clinical Features

There are considerable clinical and pathogenetic issues surrounding the management of hemorrhagic fever syndromes. Although data are incomplete, it appears that the hemodynamic patterns of dengue fever, hemorrhagic fever with renal syndrome, and hantavirus pulmonary syndrome pursue a course of progressive decrease in cardiac output with rising systemic vascular resistance. This disease course contrasts with the pattern observed in septic shock, in which an intermediate period with low resistance is present. Thus, case management of patients with hemorrhagic fever may need to differ from that of patients with septic shock.

Diagnostic Methods

Researcher performing a diagnostic test

Improving the techniques used for the diagnosis of hemorrhagic fevers has been an area of concentration for SPB over the last several years. Introduction of two special techniques, antigen-detection enzyme-linked immunosorbent assay (ELISA) and IgM-capture ELISA, has provided sensitive, acute-phase diagnostics for most purposes, and theses methods are a marked improvement over past approaches. Generally, the antigen-detection ELISA detects most cases in the acute phase of hemorrhagic diseases caused by many of the viruses that SPB studies, particularly those cases that are most in need of ribavirin therapy. The IgM ELISA provides excellent sensitivity and specificity for patients in whom antigen has disappeared or for immunopathologic conditions, such as diseases caused by hantaviruses.

Reverse transcription polymerase chain reaction (RT-PCR) is in experimental use for more exacting situations. This method promises to add to diagnostic sensitivity, with special usefulness in imported cases for which we have more laboratory and health care infrastructure available and a greater need to make an immediate exclusionary diagnosis. RT-PCR also makes viral genetic sequence information immediately available, a characteristic that made the test useful in identifying the Ebola-Zaire species during the outbreak of Ebola hemorrhagic fever in Kikwit, Zaire, in 1995.

Prevention

Campaign to rodent-proof homes to prevent HPS in Ramah, New Mexico.

Prevention of hemorrhagic fevers is often hampered because the reservoirs of the causative agents can be numerous and difficult to control. This difficulty was evident during CDC's attempts to develop control guidelines for Sin Nombre virus and deer mice in the southwestern United States in 1993 and 1994. Deer mice proved to be prolific and adaptable to a wide range of ecologic settings.

However, solid health communication efforts have been made in a number of areas relevant to hemorrhagic fevers, especially in infection control and diagnostics for health providers. In the case of Lassa fever and hantavirus pulmonary syndrome, large community education campaigns have been mounted by CDC and various collaborators, both domestic and foreign. Such efforts have resulted in increased awareness of these diseases in the affected areas.

On the vaccine front, it is evident that a lack of economic incentive hinders the development of vaccines against hemorrhagic fever viruses. Nevertheless, the potential these viruses have for causing illness and death makes it important for us to understand the principles of immunization against them. The success of the Argentine hemorrhagic fever vaccine in preventing disease shows the utility, but also the financial vulnerability, of the vaccine approach to controlling such locally important diseases.

Looking Ahead

The underlying theme of the above is clear: while we have made significant progress in understanding these viruses, the diseases they cause, and how to control them, we have much more to learn. Because such viruses can emerge in new areas and act in unexpected ways, and because new viruses keep appearing, the need to study them, control them, and prevent their spread will continue and may become even more critical in the years to come.

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This page last reviewed November 26, 2003

National Center for Infectious Diseases
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