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Category: Clinical Microbiology
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This book is the first of an annual series of books which will be based on ICAAC Symposia on Emerging Infections. The editors are in the forefront of the scientific and clinical communities dealing with emerging pathogens. Each chapter is written by an expert in the field and will cover basic science as well as clinical topics. This book and the series will be valuable and popular for a wide range of people working in the fields of infectious diseases, internal medicine, and clinical microbiology.
Paperback, 277 pages, illustrations, index.
Dengue fever and dengue hemorrhagic fever (DHF) are caused by infection with four dengue virus serotypes, dengue-1 (DEN-1), DEN-2, DEN-3 and DEN-4, which are closely related to each other antigenically. This chapter reviews the changing epidemiology associated with dengue viruses and attempts to explain why changes have occurred in the waning years of the 20th century. The reasons for the dramatic resurgence of epidemic dengue/DHF in the waning years of the 20th century are complex and not fully understood but are most likely associated with demographic and societal changes that have occurred over the past 50 years. The emphasis has thus been on implementing emergency control methods in response to epidemics rather than on developing programs to prevent epidemic transmission. This approach has been particularly detrimental to dengue prevention and control because in most countries surveillance is very poor; the passive surveillance systems relied on to detect increased transmission are dependent on reports by local physicians, who often have a low index of suspicion and do not consider dengue in their differential diagnosis of dengue-like illness. As a result, the epidemic has often reached or passed peak transmission before it is detected, and emergency control measures are nearly always implemented too late to have any impact on the course of the epidemic. Only with an improved public health infrastructure to support community-based prevention programs will we be able to reverse the trend of emergent epidemic dengue/DHF.
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.
Venezuelan equine encephalomyelitis (VEE) viruses are positive-strand, unsegmented RNA viruses in the genus Alphavirus of the family Togaviridae. The first phylogenetic analyses of the VEE complex, based on partial nsP4, El, and 3' untranslated sequences, indicated that IAB, IC, and ID viruses are closely related and have a recent common ancestor. This work also suggested that epidemic/epizootic VEE viruses evolved from ID progenitors on more than one occasion. Several hypotheses for VEE emergence were proposed, including (i) maintenance of IAB and/or IC viruses in continuous, cryptic transmission cycles; (ii) maintenance of IAB and/or IC viruses in latent equine or other animal infections; (iii) reemergence of epizootic viruses following administration of incompletely inactivated vaccine preparations; (iv) maintenance of IAB and/or IC viruses as minority subpopulations within enzootic virus populations; and (v) periodic emergence of epizootic viruses via mutations of enzootic strains. Phylogenetic studies of the two recent, northern South American VEE outbreaks have further supported the hypothesis of evolution and emergence of epidemic/epizootic IAB/IC viruses from enzootic ID-like progenitors. Current phylogenetic trees, obtained from reverse transcription-polymerase chain reaction products of 857 nucleotides derived from the E3 and E2 genes, identify three distinct monophyletic groups or lineages of epizootic/ epidemic VEE viruses. The most important gaps remaining in one's understanding of epidemic/epizootic VEE emergence concern the viral determinants of virulence and the pathogenesis changes that lead to high-viremia-facilitated transmission among equines and other large mammals.
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.
Well before Louis Pasteur's success with the vaccination of Joseph Meister, rabies evoked strong sentiments in virtually all segments of the human population, providing rich fodder for legend and literature. In 1995, rabies in foxes and cats was still significant, with cats rather than dogs now leading as the most common rabid domestic animals. The gradual transition in animal rabies has resulted in major epidemiologic changes in human rabies, with concomitant implications for postexposure prophylaxis (PEP) recommendations. Rather, human attraction to the recreational and economic benefits provided by wildlife has contributed to the reemergence of rabies as a major zoonosis. Rabies PEP consists of wound care, active vaccination, and passive immunoglobulin administration. The foundation of human rabies prevention is based on reliable identification of an exposure and the institution of prompt, appropriate PEP. The example provided by raccoon rabies is perhaps the most striking translocation story in recent years. In 1977, when the index case occurred near the Virginia-West Virginia border, one of the most intensive outbreaks of wildlife rabies in the United States began. Given the multispecies complexity of rabies and the considerable size of affected geographic areas, together with the opportunity for translocation of infected furbearers, it is unclear if traditional preventive strategies can lessen its burden on the public health infrastructure.
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 changes in the epidemiology of group A streptococcal infections and describes factors associated with the fitness and virulence of the pathogen. It also highlights the genetic diversity of group A streptococci, which, acted on by host factors, may account for periodic changes in disease severity. Childbed fever was one of the most frequent causes of death among postpartum women. A number of characteristics of group A streptococci may contribute to their fitness. These determinants can be categorized into three functional classes: adherence and colonization, invasion and replication, and avoidance of host defenses. Activation of the alternate complement pathway produces C5a, which is one of the primary mediators of chemotaxis in human tissue, attracting neutrophils to sites of infection. Horizontal gene transfer has resulted in emm-like genes and vir regulons with mosaic structures. Such an ability to recombine, in conjunction with strong selective pressures, can accelerate the evolution of functional diversity. The current increase in severe disease, particularly streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis, is most likely related to changes in serotype distribution, production of toxins, and/or other factors. As immunity to these virulence factors increases, virulence will be lost. The author believes that this resurgence of more severe group A streptococcal disease does not represent the natural selection of a more virulent clone that will predominate but rather that as population immunity increases one will once again return to periods of waxing and waning of group A streptococcal disease severity.
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.
Escherichia coli O157:H7 can cause nonbloody diarrhea, bloody diarrhea (hemorrhagic colitis), hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TIP), and death. Illness typically begins with severe abdominal cramps and nonbloody diarrhea, which often becomes bloody by the second or third day of illness. Thus, although bloody stools are common with E. coli O157:H7 infection, the diagnosis must be considered for patients with nonbloody diarrhea as well. Differential diagnosis of colitis caused by E. coli O157:H7 have been provided in this chapter. Probably the most common cause of acute renal failure in children, HUS is characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure, and central nervous system manifestations. Most information about modes of transmission of E. coli O157:H7 infection has been derived from outbreak investigations. Although most E. coli O157:H7 strains are susceptible to antimicrobial agents used for enteric infections, such treatment has not been demonstrated to improve the course of illness or to prevent complications. The authors recommend that clinicians urge their clinical laboratories to culture for E. coli O157:H7 by using sorbitol-MacConkey medium, at a minimum from stools with visible blood. They should advise patients with diarrhea and parents of children with diarrhea that washing hands with soap after bowel movements is the most important measure in preventing the spread of infection.
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.
In spite of decades of good control, in the newly independent states of the former Soviet Union epidemic diphtheria has reemerged. During the late 1980s, childhood immunization coverage levels were low in some regions of the Soviet Union. One of the factors contributing to lack of ontime vaccination of children was a long list of contraindications for vaccination. In the central Asian republics and Caucasian countries there were vaccine shortages due to disruption of the supply in 1992 and 1993, following the dissolution of the Soviet Union. Before the dissolution of the Soviet Union, Russian-manufactured diphtheria toxoid vaccine was used throughout the Soviet Union. Although morbidity data from the armed forces are not available to civilian public health authorities in the former Soviet Union, outbreaks of diphtheria among soldiers have been reported. High coverage among children (95% coverage with four doses of diphtheria toxoid in all districts) and administration of a single dose of diphtheria toxoid to each inhabitant were essential to achieve high population immunity. The risk of emergence of epidemic diphtheria in other countries is difficult to estimate, but clearly clinical and public health expertise in diagnosis and management of diphtheria cases must be maintained. Although previously a disease of children, diphtheria has emerged as an epidemic disease among adolescents and adults in the newly independent states of the former Soviet Union decades after the implementation of an effective childhood vaccination program.
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.
In 1982, researchers were able to culture and characterize Campylobacter species organisms, which they called C. pyloridis and which are now known as Helicobacter pylori. H. pylori is now known to also play an etiological role in peptic ulcer disease as well as in the development of distal gastric adenocarcinomas and gastric lymphomas. As such, a previously obscure organism has now been associated with many of the most important gastroduodenal diseases. H. pylori were initially classified as belonging to the genus Campylobacter. Epidemiological studies have used techniques like restriction fragment length polymorphism and randomly amplified polymorphic DNA PCR to exploit the heterogeneity, for example, for studies of transmission of H. pylori infection. Thus, H. pylori is an "emerging infection" with respect to our knowledge about it, but at the same time it is disappearing from the population in developed countries. The main indication for treatment of H. pylori is the occurrence of peptic ulcer disease. As such, H. pylori infection has probably been the most important emerging infection of the past decade, and the recognition of its role in peptic ulcer disease has had a major impact on health care worldwide. Several investigators have recently claimed that chronic H. pylori gastritis is associated with a variety of extragastrointestinal disorders, such as delayed growth and malnutrition in children in developed countries. The major noninvasive methods, not requiring endoscopy, are serology and breath testing.
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.
Fungal pathogens are emerging as important causes of morbidity and mortality in immunocompromised patients. Among the well-known life-threatening and deeply invasive fungi are Candida albicans (the most common cause of disseminated nosocomial fungal infection), Aspergillus fumigatus (the most common cause of nosocomial fungal pneumonia), and Cryptococcus neoformans (the most common cause of central nervous system [CNS] mycosis in human immunodeficiency virus [HIV]-infected patients). Fusarium spp. are representative of the emerging group of hyaline molds, which cause respiratory and disseminated infections in immunocompromised patients. The dematiaceous molds represent a diverse group of fungal pathogens which share the presence of melanin-like pigments in the cell wall. Infections due to azole-resistant C. albicans and non-albicans Candida species, heretofore rare events, have become commonplace. During the past decade, substantial advances have been achieved in understanding of the pathogenesis, detection, and treatment of infections with this emerging pathogen. Such approaches may provide a model for understanding other emerging fungal pathogens. The infection presents with numerous necrotic lesions, which are papulonodular lesions that may simulate those of tuberculosis, leishmaniasis, cryptococcosis, or histoplasmosis in HIV-infected patients. This infection in severely immunocompromised patients with disseminated penicilliosis has been successfully managed with amphotericin B. For mild to moderate disease, there is increasing experience with therapeutic success with itraconazole. The fungal pathogens that have emerged during the past decade have developed in an expanding population of immunocompromised hosts, new antifungal selective pressures, and shifting environmental conditions.
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.
There are two fundamental approaches to controlling emerging and reemerging infections. Some are convinced that in future decades, one of the most important emerging and reemerging infections will be caused by genetically changing influenza viruses. The most effective approach to minimizing the incidence and severity of emerging and reemerging infections is amelioration of the societal conditions that provide the milieu in which these infections arise and flourish. Potential effects of world population growth on variables related to emerging and reemerging infections have been provided in this chapter. Since the variables that influence emerging and reemerging infections are also issues that must be addressed if society is to thrive, or even survive, it is imperative that an understanding of these issues be an integral part of the education of every student. Although this discussion is focused on the American educational system, the educational changes suggested for the United States are equally applicable to other countries, both developed and developing. Individuals and their professional societies thus have the opportunity to use the growing concerns about emerging and reemerging infections to influence the body politic to take actions focused on ameliorating the societal conditions associated with such infections; doing so not only will reduce the risks of emerging and reemerging infections but will benefit the entire global community.
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.
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