Key Challenges for VSPB
The number of known disease-causing viruses has been increasing and this trend is likely to continue as evidenced by the frequency of recent outbreaks. We anticipate recognition of new pathogenic Arenaviruses, particularly from the Americas and potentially from Africa. Hantavirus pulmonary syndrome (HPS) is a widespread if uncommon problem in the Americas and is another disease of interest as new species of Hantavirus are detected. Further, new foci of disease and more virus-caused diseases await discovery and exploration.
Additionally, the behavior of known viruses is unlikely to remain static. They continue to appear in areas and in epidemiologic contexts that are unpredictable and novel for us. Recent examples include the extensive role that stockyards have played in Crimean-Congo hemorrhagic fever (CCHF) outbreaks in the Middle East; the appearance of the species Reston ebolavirus in monkeys in an unexpected part of the world (Texas); the explosive outbreak of HPS in Chile; the first recorded outbreak of Rift Valley fever (RVF) on the Arabian Peninsula; and continued and frequent outbreaks of Ebolavirus and Marburgvirus in Africa.
Transmission of the viruses causing these diseases continues to spark debate and research. Many of the viruses investigated by VSPB display some capability of infection through small-particle aerosols in the laboratory; however, the role of aerosols in transmission outside the laboratory continues to raise uncertainties.
While an aerosol route from animal reservoirs to humans is probably the dominant mode of transmission for some of these viruses (species of Arenaviruses and Hantaviruses, for example), others can transmit disease person to person after introduction from the zoonotic cycle into the human population. This usually occurs through direct contact (handling of infected patients) or by medical procedures in clinical facilities without adequate infection control procedures.
There are considerable clinical and pathogenetic issues surrounding the management of hemorrhagic fever syndromes and attention to these patients may require specific care techniques. Although data are incomplete, it appears that the hemodynamic patterns of dengue fever, hemorrhagic fever with renal syndrome (HFRS), and HPS 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 differ from that of patients with septic shock.
Improving the specificity, sensitivity, and rapidity of the techniques used for diagnosis of hemorrhagic fevers has been an area of high priority. Introduction of two important techniques, antigen-detection enzyme linked immunisorbent assay (ELISA) and IgG/IgM-capture ELISA, have provided sensitive, acute-phase diagnostics for most purposes. The IgM ELISA provides excellent sensitivity and specificity for patients in whom antigen has disappeared or for immunopathologic conditions, such as diseases caused by Hantavirus.
Reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative PCR assays are used to identify and perform genetic characterization of viruses. RT-PCR also makes viral genetic sequence information immediately available, a characteristic that made the test useful in identifying the Ebolavirus species during the outbreak of Ebola hemorrhagic fever in Kikwit, Zaire, in 1995.
The real-time assay preforms rapid and safe diagnosis with high sensitivity allowing identification of patients early in the course of disease. When complemented with antibody assays, this combination can detect a large number of cases quickly which has been useful in outbreak settings providing on-site diagnosis of cases and facilitating further control efforts.
Prevention of hemorrhagic fevers is often difficult because the virus reservoir may be unidentified or numerous and difficult to control. This difficulty was evident during CDC's attempts to develop control guidelines for Sin Nombre virus, a common causative agent of HPS, 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 HPS, 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 affected areas.
With regard to vaccines, a lack of economic incentive hinders development of vaccines against hemorrhagic fever viruses. Nevertheless, the ability of these viruses to cause illness, even death, makes it important for us to understand the principle of the immune response so that development of potential vaccines can occur. The success of the Argentine hemorrhagic fever vaccine in preventing the disease in the endemic area in Argentina demonstrates the utility of the vaccine approach in controlling locally important diseases.
Although we have made significant progress in detecting and understanding viral hemorrhagic fevers and disease and the causative viruses, we have much more to learn in terms of control methods. The nature of outbreaks is dependent on the human cultural practices and ecological parameters that define the natural cycle of both the virus and its reservoir hosts. Because viruses can emerge in new areas and act in unexpected ways, and because new viruses keep appearing, there is a continued need for rapid response, specialized research, creation of preventative or control methods, and active communication between researchers and the greater community.