Biological Warfare and Bioterrorism: A Pathologist’s Perspective

Wun-Ju Shieh, M.D., M.P.H., PH.D.

(presented at the CAMS 2003 Annual Scientific Meeting)

The tragic event of the terrorist attacks on September 11 and the juxtaposed anthrax outbreak have impacted profoundly on the society in the United States and worldwide. These events have transformed a theoretical threat to harsh reality, and clearly illustrated the United States’ homeland is vulnerable to such hostile attack. These events also demarcated the beginning of a novel form of warfare in the 21^st century. In an era of expanding global communications and increasing trade and travel, countries or small groups of terrorists can directly attack the United States’ homeland without using conventional military weapon. The potential use of biological agents causing detrimental diseases, such as anthrax, plague, smallpox, etc. is particularly disconcerting. The potential lethality of these agents can be extremely high while the manufacture cost of them is much lower than chemical or nuclear weapon. To increase the capacity of handling a large-scale bioterroristic attack, two major forms need to be taken: 1) intelligence and law enforcement activities to prevent attacks, and 2) medical and public health activities to prepare for, respond to, and lessen the impact of attacks. With regard to the latter, our medical and public health systems must be an integral part of a multifaceted and comprehensive preparation.

 Pathologists and medical examiners are essential partners in bioterrorism (BT) preparedness. They play an important role in the response to a known biological attack as well as in the surveillance for a covert attack because of their expertise to investigate deaths that are sudden, suspicious, violent, unattended, and unexplained in nature. The principal investigative tool of the pathologists is the autopsy procedure that enables them to identify the dead, observe the condition of the body, and deduce the cause and manner of death. Autopsies are valuable in diagnosing unrecognized infections, evaluating therapy, understanding the pathogenesis and route of infection for uncommon or emerging infections, and in developing evidence for subsequent legal proceedings. The same algorithm and principle apply to the investigation and surveillance of biological warfare or BT events.

           The consequence of biological warfare or BT event can vary from a minimal effect to disruption of ongoing activities, emotional reaction, illness, or death. The list of potential biological warfare and BT agents is long, however, they have been prioritized as Category A, B, and C based on the risk to national security level. The importance of recognizing the pathological features of these different agents was illustrated by the inhalational and cutaneous anthrax cases that occurred in the United States during October 2001 The autopsy on the index inhalational anthrax case was performed to determine the exact route of infection (cutaneous, gastrointestinal, or inhalational). Once inhalational anthrax was diagnosed, public health officials were able to better define potential sources of airborne B. anthracis spores.

 Pathology diagnostic procedures for these BT agents should include routine microscopic examination and combine with the collection of specimens for additional tests that will aid in determining a definitive organism-specific diagnosis. Blood, cerebrospinal fluid, and tissue samples or swabs should be placed in transport media that will allow bacterial and viral isolation. Serum should be collected for serological and biological assays. A portion of tissue sample needs to be frozen for polymerase chain reaction (PCR) testing. Tissue samples should also be placed in electron microscopy fixative for possible ultrastructural studies. Microscopic examination of formalin-fixed, paraffin-embedded tissues stained with hematoxylin and eosin (H&E) is indispensable because it can characterize the patterns of tissue damage defining a syndrome, and subsequently leading to a list of possible microorganisms in the differential diagnosis. Special stains, such as tissue Gram and silver impregnation stains, can be helpful in identifying bacterial agents. Specific immunohistochemical (IHC) assays for many BT agents have been developed at IDPA/CDC. These IHC tests can be performed on formalin-fixed tissues and paraffin-embedded blocks. They provide a sensitive, specific, and safe way for rapid diagnosis of emerging infections and have been the mainstay in many outbreak investigations.  

 (Dr. Shieh is Senior Staff Pathologist, Infectious Diseases Pathology Activity, National Center for Infectious Diseases, CDC, Atlanta, GA.)