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Category: Clinical Microbiology
Emerging Infections 4 is the fourth of an annual series of books based on ICAAC Symposia on Emerging Infections. It provides a complete and updated discussion of new and emerging infectious diseases, covering both basic science and clinical topics. The editors are in the forefront of the scientific and clinical communities dealing with emerging pathogens. This book and the series will be valuable to a wide range of people working in microbiology, infectious diseases, epidemiology, public health, and clinical medicine.
Electronic Only, 218 pages, illustrations, index.
Respiratory syncytial virus (RSV) was discovered more than 4 decades ago. Infants who have been hospitalized with RSV bronchiolitis have been well described as having a predilection to experience recurrent wheezing. The majority of these children appear to be clinically normal for years but are at risk for having abnormal lung function later in life. An increase in asthma among children in the United States and some other countries has been documented, and the morbidity associated with asthma has risen disproportionately in certain lower-income and minority populations, the same groups who are most likely to acquire RSV infection early and more severely. Of increasing importance is RSV's ability to become an opportunistic pathogen in immunocompromised patients. A study by researchers indicates the significance RSV as a cause of admissions for lower respiratory tract disease in previously healthy adults of all ages. In this study of community-acquired lower respiratory tract infections in individuals 18 years of age or older, RSV caused 4% of the admissions. The first means of prophylaxis was only recently made available with the 1996 licensure of high-titered polyclonal RSV immunoglobulin to RSV, which is administered intravenously once a month. The currently available technology and candidate vaccines, although not yet perfected for use in infants, may be suitable and rapidly developed for varied older populations at risk for RSV illness and its complications.
The global pandemic of human immunodeficiency virus (HIV) infection represents a prime example of an emerging infection. The HIV pandemic has wreaked the majority of its havoc in the developing world, whereas drug-resistant HIV has been a problem among the more privileged economies. It was learned that the use of protease inhibitors as monotherapy or when added to an ongoing regimen was substandard practice, and patients failed with resistant virus. This was followed by another discovery that analogous to tuberculous chemotherapy, prescribing an optimal regimen without the education and support system to encourage patient adherence is no accomplishment and may lead to multiple-drug resistance. One significant difference between tuberculosis and HIV is that the former can be cured. The levels are highest in primary infection, which may be the most infectious period. The genetic barrier to viral escape will have to be raised in using combinations that require multiple mutations and incompatable mutations. The pharmacologic aspects of chemotherapy needs improvement, as many of the protease inhibitors that have relatively short half-lives give trough levels that are really borderline or suboptimal. Drug levels in the various tissue compartments that may represent pharmacologic sanctuaries will have to be attained. It has been learned from multiply resistant tuberculosis that the natural history resembled untreated tuberculosis, especially in the immunosuppressed.
The first torovirus was isolated from a horse with diarrhea in Berne, Switzerland, in 1972 and reported in 1983. The Berne virus grows well in cell lines such as mule skin fibroblasts, but the bovine counterpart, Breda virus, and the human toroviruses have yet to be grown in cell cultures. Toroviruses have been found to infect other domestic animals in studies based either on direct characterization of the virus, as in the case of the porcine torovirus, or on the presence of antibody to the Berne and Breda viruses. Seroconversion to torovirus as measured by the hemagglutination inhibition assay was more common in immunologically normal patients than in immunocompromised patients. In this study setting, bacterial pathogens were noted in a small fraction of both the torovirus group and the rotavirius/astrovirus group. In analyzing the disease caused by torovirus in humans, it is relevant to consider the presentation of torovirus infection in other animals. As was observed with the human toroviruses, the sequences of representative amplicons from the noncoding 3' end of the genomes were very similar, but they differed from each other and from the prototype Breda virus. Finally, torovirus was found significantly more frequently among calves symptomatic for diarrhea than among asymptomatic controls. The sequence information on the genomes of the Breda and the human viruses has been critical for the design of new diagnostic tests to place the diagnosis of these viruses on a firmer basis.
The human enteric caliciviruses, previously known as the Norwalk family of viruses, the "classic human caliciviruses," or the small round-structured viruses, are a group of enteric pathogens that are a common cause of gastroenteritis in children and adults alike. When the gene encoding the capsid was expressed in baculovirus, the resulting protein self-assembled into virus-like particles that looked like natural virus by electron microscopy (EM) and provided replenishable reagents for serologic testing, structural studies, and antigen to develop immunoassays for antigen detection. These molecular discoveries and diagnostic advances have permitted researchers to reassess the clinical and epidemiologic features of illness caused by the caliciviruses and to reconsider public health approaches to their prevention and control. This chapter provides a review to highlight some of the advances in our understanding of calicivirus-associated gastroenteritis following the introduction of new molecular diagnostics, with illustrations drawn from several recent epidemic investigations. Tracing some epidemics back to their source has extended the use of diagnostics to the detection of viruses in contaminated food and water. Despite the major advances in the knowledge of the caliciviruses based upon the understanding of their sequence and molecular organization, the search for simple diagnostic assays has been difficult. Nonetheless, in the process of sequencing many strains, the human enteric caliciviruses fell into two distinct genera. The ability to sequence polymerase chain reaction (PCR) products made it possible to trace the molecular epidemiology of caliciviruses in outbreaks of disease.
Human monkeypox was first identified in 1970 in the Democratic Republic of the Congo (DRC) in an area where smallpox had been eliminated about 2 years previously. Monkeypox, a zoonotic and probably respiratorily acquired disease, resembles smallpox clinically but differs biologically and epidemiologically of all these differences, the most important is that spread between humans is limited. Experimental monkeypox infections in several species of animals, including nonhuman primates, have demonstrated infectivity and pathogenesis following infection by aerosol, intranasal inoculations, or parenteral administration. Numerous infections and other syndromes that cause papulovesicular and vesiculopustular eruptions can resemble human monkeypox. Clinical manifestations of human diseases caused by poxviruses have been provided in this chapter. There was evidence to suggest cocirculation of varicella-zoster virus, as five of six active monkeypox cases living in one household also had serological evidence (IgM) of recent varicella-zoster virus infection. In January 1999, the Technical Advisory Group Meeting on Human Monkeypox was convened by the World Health Organization (WHO). The advisory group reviewed the clinical, epidemiologic, and laboratory results from the recent outbreaks and identified areas for further surveillance and research on the public health impact of human monkeypox. The WHO document on collection, storage and shipping of specimens from humans for monkeypox and hemorrhagic viruses should be updated.
This chapter focuses on the use of newer sequence-based methods for discovering novel microbial pathogens and some of the questions raised concerning interpretation of experimental findings. A remarkable degree of microbial diversity has recently emerged from surveys of natural environments that rely on direct acquisition and analysis of microbial gene sequences. Specialization and adaptation to an animal host are believed to involve acquisition of blocks of genes that encode virulence-associated attributes. The use of host markers to measure and predict host inflammation is not new. Two strategies are invoked by those who seek to identify novel or unrecognized microbial pathogens. The first is based on the straightforward notion that these pathogens will be found where there is unexplained disease, and in particular, disease that bears traditional features of infection. The second strategy is based on the observation that pathogens are often found within environmental niches that provide access to more privileged anatomic sites within a host. In addition to the distribution of microbial sequences and other signatures within the human body, the issue of kinetics must be confronted. With increasing experience comes appreciation of subtlety. This holds especially true for the use of microbial sequence-based detection methods. Broad-range ribosomal DNA (rDNA) polymerase chain reaction (PCR) frequently reveals bacterial sequences that are similar to but do not perfectly match any sequence in the available databases.
Epidemiologic studies of outbreaks and sporadic cases of listeriosis have increased the understanding of important sources of Listeria monocytogenes in human illnesses and have conclusively shown that both epidemic and sporadic illness are due primarily to foodborne transmission. Improved laboratory techniques for detection and subtyping of L. monocytogenes have also contributed to our understanding of the epidemiology of human listeriosis. Clinical syndromes associated with infection with L. monocytogenes are tabulated in this chapter. The chapter briefly reviews the biology of the organism, manifestations of the illness in humans, and the historical background of listeriosis in the United States. It concludes with brief remarks on diagnosis, treatment, and prevention strategies. The link between listeriosis and cancer, particularly lymphoreticular malignancies, was first reported in 1967 and confirmed in subsequent reports. The major consequences of listeriosis during pregnancy are fetal loss and neonatal disease. Due to the potential adverse outcomes of maternal listeriosis and the availability of effective treatment, it is prudent to evaluate all febrile episodes during pregnancy with blood cultures. Since many immunosuppressed patients have a decreased ability to clear infected cells, antibiotic treatment for 3 to 6 weeks may be prudent. Trimethoprim-sulfamethoxazole drug combination has proved effective in patients with listeriosis who have hypersensitivity to penicillin. Understanding of the epidemiology of listeriosis has recently been enhanced by subtyping methodologies that have clarified links among strains infecting patients and those found in contaminated foods.
The inclusion of the group B streptococcus (GBS) in a book on emerging infections published in 2000 may puzzle some readers, since GBS was recognized as a new clinical problem three decades ago. By 1938, however, Fry reported three fatal postpartum maternal infections caused by GBS which presented as pneumonia with multiple liver abscesses and two cases of puerperal sepsis complicated by endocarditis. The responsibility for decisionmaking regarding GBS disease was diffused—therapy for neonatal infections was the province of pediatricians, but interventions to prevent this disease had to be administered by obstetric care givers before delivery. In the screening-based approach, women are screened at 35 to 37 week's gestation, and those who are GBS carriers are offered intrapartum antibiotics. The recommendations appear in the book Guidelines for Perinatal Care, published jointly by American College of Obstetricians and Gynecologists (ACOG) and American Academy of Pediatrics (AAP). While reported practice may be suggestive of increased prevention, the most important benchmark is whether actual disease patterns are altered. Antibiotic prophylaxis was intended to reduce maternal to infant transmission of GBS. Various unintended consequences are potential concerns, and monitoring systems or evaluation projects have been developed to assess some of them. Antibiotic resistance among GBS and other organisms was a major concern. To date, several investigators have evaluated GBS strains from recent patients for susceptibility testing. Clinicians can reduce the chances of serious anaphylaxis by taking very careful histories of penicillin allergy from patients.
Many novel Helicobacter species are now known to play a role in naturally occurring gastrointestinal diseases in humans and several species of animals. This chapter provides an overview of the enterohepatic and gastric helicobacters (other than H. pylori) and their emerging role as important gastrointestinal pathogens with zoonotic potential. Enterohepatic helicobacters such as H. cinaedi, H. fennellwe and H. westmeadii have been discussed in the chapter. H. cinaedi, previously classified as C. cinaedi(CLO-IA), was first isolated from the lower bowel of homosexual men with proctitis and colitis. In a retrospective study of 23 patients with H. cinaedi-associated illness, 22 had the organism isolated from blood using an automated blood culture system where a slightly elevated growth index was noted. This study also described a new H. cinaedi-associated syndrome, consisting of bacteremia and fever accompanied by leukocytosis and thrombocytopenia. Non-H. pylori gastric helicobacters including H. heilmannii and H. felis are discussed. The various Helicobacter spp. and their associated diseases in numerous hosts allow us the means to assess pathogenic mechanisms, as well as the utility of these in vivo models to develop various therapeutic and prophylactic strategies to eradicate or prevent Helicobacter-induced gastrointestinal disease in humans. The ultimate goal of these studies will be to eliminate afflictions causing significant human morbidity and mortality in both the developed and the developing worlds.
Noncholera vibrio infections have emerged as an important public health concern in the United States, Canada, Japan, Taiwan, and many other countries. The majority of noncholera vibrio infections are food-borne, and the major food vehicle is raw molluscan shellfish. Most noncholera vibrios are halophilic (or salt-requiring), and their growth is enhanced by specific ranges of salinity, water temperatures, and pH. The number of noncholera vibrio infections has increased over the past few years, after years of remaining relatively stable. Over the past 10 years, Vibrio parahaemolyticus and V. vulnificus have been the most commonly isolated noncholera Vibrio species. Among the 553 culture-confirmed v. vulnificus infections reported to CDC between 1988 and 1998 through the Vibrio Surveillance System, 44% were classified as primary septicemia, 43% as wound infections, and 7% as gastroenteritis, while 6% were from other or unknown sites of infection. Noncholera Vibrio strains that cause gastroenteritis are usually susceptible to antimicrobial agents used for enteric infections, although most cases of gastroenteritis are mild and self-limited, and they can effectively be treated with oral rehydration. On the other hand, wound and primary septicemia infections require antimicrobial treatment to improve the course of illness and prevent complications. The author recommends that consumers avoid eating raw or undercooked oysters, especially during the warmer months because illness is associated with consuming oysters harvested from warm water. Due to the recent increase in noncholera vibrio infections, all states should consider making infection with any Vibrio species reportable.
This chapter demonstrates the power of Cryptosporidium parvum tiny parasite to alter human health. It focuses on recent observations and highlights current areas of uncertainty. Regardless of the exact taxonomy of Cryptosporidium species, numerous studies now indicate that C. parvum isolates exhibit considerable molecular heterogeneity. A study by researchers indicates that bovine genotype isolates do have variable virulence for humans and makes it perfectly clear that C. parvum is a very infectious parasite. In this study, healthy human volunteers serologically negative for anti-C. parvum antibodies were infected with one of three bovine genotype Cryptosporidium isolates. Studies of waterborne Cryptosporidium disease, children in developing countries, and AIDS patients as well as data examining the course of C. parvum infection in healthy volunteers illustrate the complexity of clinical cryptosporidiosis. The understanding of the mechanisms by which C. parvum infection stimulates intestinal secretion to cause diarrheal disease remains incomplete. However, a variety of observations have facilitated one's ability to develop a working model of disease pathogenesis due to C. parvum. Only effective highly active antiretroviral therapy has been clearly shown to result in the resolution of C. parvum disease in AIDS patients due to improved host immune function.
In the late 1970s, the first clues that an epidemic due to human immunodeficiency virus type 1 (HIV-1) was beginning to unfold were the opportunistic infections that clinicians recognized in previously healthy individuals who, by the laboratory parameters available and in use at the time, appeared to have no underlying disease. Opportunistic infections continue to occur in HIV-infected individuals in the United States in 2000. Epidemiologic data concerning the frequency of opportunistic infections in the era of highly active antiretroviral therapy, as well as specific studies of clinical outcome for patients enrolled in clinical trials, clearly demonstrate that highly active antiretroviral therapy (HAART) reduces susceptibility to opportunistic infection. Viral load is an independent predictor of the likelihood of developing opportunistic infections, but the risk of developing such complications is still effectively predicted by the current CD4+ T-lymphocyte count. The revised United States Public Health Service-Infectious Disease Society of America guidelines on prophylaxis of opportunistic infections, which were published in August 1999, continue to stress the importance of initiating primary prophylaxis for pneumocystosis, Mycobacterium avium complex disease, toxoplasmosis, and tuberculosis for patients who meet the well-established criteria.
Since the publication of 1992 Institute of Medicine (IOM) report Emerging Microbial Threats, a factor in microbial emergence that has attracted an increasing degree of attention, is the possibility of deliberate release of pathogenic microbes for the purpose of biological warfare or bioterrorism. The factors that facilitate the spread of naturally occurring microbes would also contribute to the potential for even a small, deliberate introduction of smallpox virus to develop into a global pandemic. It is ironic that global eradication of smallpox virus, justifiably heralded as an unequivocal triumph of modem medicine, indirectly contributed to this modem vulnerability. The Department of Defense (DOD)-Health and Human Services (HHS) joint research plan addressed three scientific goals including diagnostics, vaccines, and antiviral drugs. In 1995, detection and identification assays for orthopoxviruses were predominantly immunologically based. Significant enhancements based on detection of viral genomes by PCR, coupled with emerging technologies such as 5' nuclease PCR assays capable of detecting single-base polymorphism in miniature analytical thermocycling instruments, were being developed. The second scientific objective of the DOD-HHS program was to evaluate the protective efficacies of existing smallpox vaccines against an aerosolized variola virus exposure. The third objective was development of an antiviral drug such as DNA polymerase inhibitors, reverse transcriptase inhibitors and IMP dehydrogenase inhibitors to treat smallpox patients.
There is considerable controversy as to which biological agents should concern us, either for defense against military use or, for defense against terrorism. The mosquito-transmitted yellow fever virus is classified as biosafety level 3 (BSL 3), but it is aerosolinfectious and has a high case fatality, which are ameliorated by the existence of a very effective vaccine. The viral hemorrhagic fever (VHF) has appropriate properties for aerosol weapons, and this chapter concentrates on three viruses: Machupo virus, Rift Valley fever (RVF) virus, and Marburg virus. The RVF virus is the most stable of the VHF when stored in the liquid or frozen state. Intravenous ribavirin would be expected to be fairly effective against Machupo virus and perhaps helpful in RVF, but stocks are limited and not readily accessible. VHF seems to be very likely agents for lethal state-sponsored actions against large numbers of people. The severe dramatic disease they produce, with its attendant need for intensive supportive care, would increase their impact. Education of clinicians is extremely important as well and is occurring in the context of both travel medicine and bioterrorism defense.
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