Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.

Clinically, the combination of fever and hemorrhage can be caused by many pathogens, including viruses, rickettsiae, bacteria, protozoans, and fungi. However, the term viral hemorrhagic fever (VHF) is usually reserved for systemic infections characterized by fever and hemorrhage caused by a special group of viruses that belong to four different families: Filoviridae, Arenaviridae, Bunyaviridae, and Flaviviridae. All members are lipid-enveloped RNA viruses; except for filoviruses, where the resorvoir remains unknown, these viruses are transmitted to humans by arthropods and rodents. The VHFs are characterized by abnormal vascular regulation and damage. The VHFs all have similar clinical pictures with mortality rates of 15-30% or in the case of Ebola virus, up to 80%. Between 1993 and 2001, more different VHFs and related diseases were reported than during any comparable period over the past several decades. These diseases include Ebola VHF in Uganda in 2000, in Zaire in 1995 and in Gabon between 1994 and 1996; ongoing cases of Marburg hemorrhagic fever in the Democratic Republic of Congo beginning in 1998; Rift Valley fever in Saudi Arabia and Yemen in 2000 and in Kenya in 1997; Lassa fever in Sierra Leone in 1997; hantavirus pulmonary syndrome in the Americas since 1993; and imported cases of dengue hemorrhagic fever from Central and South America, and yellow fever from Africa during the 1990s.

During the 20th century, the advent of vaccines and antibiotics, and continued improvements in urban sanitation and water quality resulted in a dramatic decline in mortality due to infectious diseases. There was a brief period of optimism in the mid-1900's that infectious pathogens would no longer be a significant cause of death in the United States. For a number of reasons, this trend had reversed by the end of the century, and the rates of death caused by infectious diseases began rising. in recognition of this change, the Institute of Medicine issued a report in 1992 that called attention to the major factors contributing to the emergence and reemergence of infectious diseases. Among these were the following: increased human encroachment on wilderness habitats, resulting in changes in the ecosystem and increased contact with animal and insect vectors which may harbor unknown infectious agents; sizable growth in human population, resulting in increased urbanization and crowding; increased global travel; changes in human behaviors; and microbial evolution.

An increase in cases of acute febrile encephalitis occurred in Western Malaysia between September 1998 and May 1999, and a similar illness was reported in Singapore in March 1999. Most cases occurred in males who had been exposed to pigs, or among abattoir workers, and at least 100 deaths were reported. The illness was characterized by fever and headache, followed by drowsiness and disorientation; patients with severe cases developed seizures and coma within 24 to 48 hours. Concurrently, there were also illnesses and deaths among pigs in the same region, although the symptoms predominantly involved the respiratory system, and only a few pigs had signs of neurologic disease. From a cerebral spinal fluid specimen from a human patient, Dr. Chua and colleagues were successful in isolating a virus that was morphologically identified as belonging to the family Paramyxoviridae, and is now known as Nipah virus.

During April-July 1998, an increase in fatal cases of neurologic disease in young children occurred in Taiwan, with at least 55 fatalities reported. Concurrently, an outbreak of hand, foot, and mouth disease (HFMD) was also occurring. In fatal cases, the acute illness was characterized by fever, or rash, or mouth ulcers, followed by a rapid cardiopulmonary failure; death frequently occurred within 24 hours of hospitalization. Approximately three-fourths of the fatalities were in children less than 3 years of age. We report here the findings from autopsy specimens from two of the fatal cases of encephalomyelitis.

In Case 1, a 9-year-old female, H&E sections of central neurologic system (CNS) tissue showed perivascular infiltrate, areas of inflammation, necrosis, and neuronal degeneration. Immunohistochemical (IHC) staining was positive when using a monoclonal antibody for enterovirus 71 (EV71), a picornavirus associated with HFMD.