Emerging Infections 1

This chapter concentrates on the arena viruses and presents some recent findings on Ebola virus and other hemorrhagic fever viruses. The viral hemorrhagic fevers all have similar clinical pictures, with mortality rates of 15 to 30%, or in the case of Ebola virus up to 80%. Between 1993 and 1996, an increasing number of different viral hemorrhagic fevers and related diseases were seen in any other comparable period over the past 3 decades. The previously known Zaire subtype of Ebola virus caused an epidemic in Kikwit, Zaire, largely through nosocomial amplification and person-to-person transmission. The arenaviruses responsible for naturally occurring human disease are listed in the chapter. There are at least two tools to deal with the shifting, growing target, and there is also the vaccine against Junin virus, which has the possibility to eliminate human disease from Argentine hemorrhagic fever, the largest public health problem caused by the American arenaviruses. One can approach the prevention or treatment of most of the hemorrhagic fevers optimistically, but Ebola virus prevention and treatment still elude us.

This chapter describes the outbreaks of disease caused by Megamyxovirus zoonotic agent; provides an updated description of the virus, its genome, and its wildlife reservoir; and documents what is known of the pathology and pathogenesis of equine morbillivirus (EMV) infection. A severe outbreak of respiratory disease occurred in the second half of September 1994 in horses stabled in the Brisbane suburb of Hendra. The outcome of the outbreak was that 13 horses died. The trainer died after hospitalization with severe respiratory involvement, while the stable hand recovered after a protracted illness. Although horses had been moved off the property during this period, infection had not spread to distant sites and extensive surveillance showed that the virus was not active in horses or humans. In fluorescent-antibody tests, sera from naturally infected horses and humans reacted strongly with the fruit bat virus. Identical viruses were isolated from a range of tissues from horses infected during the initial outbreak and from a kidney of the deceased trainer. Morphologically the virus is a member of the family Paramyxoviridae. The pathology of field and experimental EMV infections in horses and experimental infections in cats has been described. It is sufficiently different from known members of the Paramyxoviridae to be considered a member of a new genus which bridges the two existing genera Paramyxovirus and Morbillivirus. The author proposes that consideration should be given to creating a new genus within the family Paramyxoviridae, subfamily Paramyxovirinae, to be called Megamyxovirus, with the type species being EMV.

Phylogenetic analysis based on 16S rRNA gene homology places organisms currently designated Ehrlichia spp. within three different clusters. The theme of evolution for survival as obligately intracellular organisms within insects and ticks seems to characterize most of those bacteria well, except for those in the group containing Ehrlichia sennetsu and Neorickettsia helminthoeca. The etiologic organisms of human monocytotropic ehrlichiosis (HME) and human granulocytotropic ehrlichiosis (HGE) have surely been present on Earth for eons. The body of knowledge provided by veterinary scientists, including techniques to cultivate some of the Ehrlichia spp. as antigens for immunofluorescence serology and descriptions of their microscopic and ultrastructural appearance, facilitated the identification of the etiologic agent of HME as an Ehrlichia sp. Increasing numbers of commercial laboratories are offering serologic and PCR diagnostic assays for the diagnosis of the human ehrlichioses. A commercial laboratory with the most experience in the diagnosis of HME, demonstrated the presence of antibodies to E. chaffeensis in 1,136 serum specimens between October 1991 and May 1996. Cell culture recovery of the HGE agent in HL60 cells (a human myeloid cell line) has yielded more isolates than recovery of E. chaffeensis has in DH82 cells. HGE is treated successfully with doxycycline with the same doses as for HME. Based on cell culture antimicrobial susceptibility studies, rifampin, rifabutin, and selected fluoroquinolones show promise as alternative drugs that might prove useful in situations such as pregnancy.

This chapter reviews several recent surges in disease activity caused by the three main meningococcal serogroups (A, C and B) in the 1990s and discusses current and future strategies for prevention. The mortality rate of untreated meningococcal meningitis has not been recorded recently but was reported to be as high as 75% in the preantibiotic era. The precise reason for the distinct seasonality is unclear but may be related to the drying effect on mucous membranes, seasonal transmission of respiratory viruses, or other factors. More importantly, drying of the nasopharyngeal mucosa or intercurrent respiratory tract infections may contribute to invasiveness, transmission of carriage, or both. Complete immunization coverage with the polysaccharide vaccine is critical to halt epidemic disease. In the early 1990s, public health personnel in Oregon noticed increasing rates of meningococcal disease in the general population but surprisingly not in focal outbreaks. The epidemiologic pattern of disease was similar to endemic patterns in most respects, including seasonality, sex distribution, and mortality rates. A constant low level of disease is caused by a variety of serogroups and, within each serogroup, a variety of individual strains. The recent history of meningococcal disease outbreaks due to serogroups A, B, and C suggests that epidemic strains will continue to arise and cause major public health crises in both developing and developed countries.

Bartonella species have become recognized as substantial human pathogens associated with a wide spectrum of diseases. Four members of the genus are known to cause human infection: Bartonella bacillifarmis, B. henselae, B. quintana, and B. elizabethae. Bacillary peliosis hepatis (BP) is a different vasculoproliferative histopathological entity that occurs in the liver and spleen and occasionally in lymph nodes. Patients with BP can develop thrombocytopenia or pancytopenia and elevated levels of hepatic enzymes, most commonly increased alkaline phosphatase. Bartonella can be isolated directly from the cutaneous lesions of bacillary angiomatosis (BA), but recovery is even more difficult and may require cultivation of biopsied tissue with endothelial cells for weeks. It is likely that cat scratch disease (CSD) is the most commonly recognized Bartonella infection of humans, affecting at least 22,000 people each year and costing more than $12 million annually for diagnosis and treatment in the United States alone. The identification of B. henselae as the agent of CSD and the ability to culture this organism and detect antibodies to it have better defined the spectrum of CSD infection. As with other Bartonella species, the transmission of these four Bartonella species among small mammals is presumed to occur via arthropod vectors. Infection in immunocompromised hosts is associated with an unusual stimulation of vascular proliferation (BA), while infection with the same species, B. hensetae, causes an entirely different histopathological response (CSD) in immunocompetent hosts.

This chapter provides a description of the three zoonotic diseases now known to be transmissible to humans by the deer tick, Ixodes scapularis (also known as Ixodes dammini). The convergence of these and other organisms within the Lyme disease transmission cycle may represent a clinical challenge as well as a scientific opportunity to study the immunologic interactions of pathogens in a naturally occurring model of coinfection and cotransmission. Because the three infections may require different approaches to therapeutic management, development of an understanding of the natural history of infection with Babesia and Ehrlichia spp. may become critical to understanding their importance in the Lyme disease transmission cycle. Application of broad-range PCR and other pathogen discovery techniques has the potential to expand the litany of pathogens known to be transmitted by deer ticks, with the ultimate goal of clarifying the role of the known and perhaps soon-to-be-known cold-zone pathogens within the transmission cycle of Lyme disease. White-footed mice appear to be a reservoir for all three of these known human pathogens (Borrelia, Ehrlichia, and Babesia) and are commonly coinfected themselves. Further research is necessary to define the full complement of microbial agents involved in the Lyme disease transmission cycle and to elucidate further the possible immunologic interactions of these pathogens.

This chapter expands the historical perspective to the present and describes recent developments in mycobacteriology in order to improve clinicians’ ability to consider nontuberculous mycobacterial disease in a variety of settings and to facilitate laboratories’ ability to isolate the more unusual and fastidious pathogens. The first reports of human infections due to the nontuberculous mycobacterial species and their environmental sources, geographic distributions, and animal reservoirs and manifestations are outlined. A table provides a list of the four major disease presentations currently associated with the nontuberculous mycobacteria (pulmonary disease, lymphadenitis, cutaneous and soft tissue infections, and the recently described disseminated infections) and the major host risk factors. Other organisms associated with lymphadenitis include Mycobacterium celatum, Mycobacterium genavense, Mycobacterium haemophilum, Mycobacterium kansasii, Mycobacterium malmoense, Mycobacterium scrofulaceum, and the rapidly growing mycobacteria. Direct inoculation of mycobacterial organisms present in soil or water via trauma may lead to skin or soft tissue infection. The fluorochrome acid-fast stain permits more rapid examination of smears than does the traditional Kinyoun or Ziehl-Neelsen stain, and it is now considered the preferred method. Laboratories must employ rapid diagnostic and antimicrobial susceptibility tests and be prepared to detect relatively fastidious species of mycobacteria. Clinicians should realize that, although there is a lack of standardized drug testing methods for the slowly growing nontuberculous mycobacteria, testing of initial isolates can be helpful if a comparison of results with those for subsequent isolates suggests developing resistance.

The sometimes desperate search for an etiology of severe, life-threatening, and persistent diarrhea in patients with AIDS has led attention to three "new" or emerging protozoan enteric pathogens: Cryptosporidium, Cyclospora, and microsporidia. All three of these emerging enteric protozoa disrupt the intestinal epithelium and tend to cause persistent diarrhea. A recent longitudinal review in a community hospital suggests that elderly patients may also be predisposed to cryptosporidiosis, as 36% of infected patients in the study were 63 years of age or older. The prognosis is clearly better in individuals whose CD4 counts return toward normal, and preliminary results from two studies evaluating the efficacy of highly active antiretroviral therapy document improvement in either diarrhea or parasite shedding in patients with cryptosporidiosis or microsporidiosis. Since glutamine-coupled sodium absorption remains largely intact (and may be superior to glucose), oral rehydration and nutrition therapy (ORNT) holds promise both in rehydration and in speeding repair of disrupted bowel function in patients with cryptosporidial and other persistent diarrheas. Cyclosporiasis appears to have a striking summer rainy-season seasonality like cryptosporidiosis and has been associated with drinking contaminated water despite apparently adequate chlorination. Cryptosporidium, Cyclospora, and microsporidia clearly pose increasingly recognized threats to both immunocompetent and immunocompromised individuals through food and water supplies. Improved detection and animal models are needed in order to better understand the pathogenesis and epidemiology of Cyclospora infections, and little is known about the reservoir and potential vehicles and means of transmission of microsporidia.

A report developed by an expert committee under the leadership of Joshua Lederberg and Robert Shope highlighted many of the infectious diseases that have been identified during the past 25 years and identified six major factors that contribute to disease emergence and reemergence. Over half of the 15 recommendations were targeted at the Centers for Disease Control and Prevention (CDC), and most of those were directed at the National Center for Infectious Diseases (NCID). The CDC strategic plan contains four goals. The first goal stresses the need to strengthen surveillance and response capacity, the second identifies a number of research priorities, the third focuses on the need to strengthen prevention and control programs at the local, state, and national level, and the fourth focuses on the need to repair the public health infrastructure required to prevent and control infectious diseases, which has deteriorated over the past 20 to 30 years. A CDC extramural research program was expanded in 1997 to address the epidemiology of hepatitis C and the need for improved diagnostic tests for a number of emerging infectious diseases. This research program is complementary to the research agenda of the National Institute of Allergy and Infectious Diseases.