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INTRODUCTION

TO THE FOURTH EDITION

It has been almost a decade since the 3rd edition of this text was published. Much has happened in the world of infectious diseases during this time. First, there has been recognition that the problems of infectious diseases are truly global and that infectious diseases in one part of the world can be quickly transmitted to another. Prime examples of this were the severe acute respiratory syndrome (SARS), the 2009 H1N1 influenza A virus outbreak, and multidrug-resistant Gram-negative bacilli (MDR-GNB). Genes for multidrug resistance can be carried on extrachromosomal genetic elements, facilitating the spread of these drug resistance determinants to highly virulent organisms such as was seen in the Shiga toxin-producing Escherichia coli (STEC) outbreak due to the O104 serotype in Germany in 2011. These emerging pathogens are literally a plane ride away, no matter where they are found globally, and can be disseminated worldwide in a matter of days to weeks.

MDR-GNB, environmental mycobacteria, and molds are emerging as important pathogens in the ever-expanding population of immunocompromised hosts. These organisms, although of comparatively low virulence when compared to highly adapted human pathogens such as Streptococcus pneumoniae or group A streptococci, have distinct characteristics that make them very worrisome. First, they have evolved over millions of years, adapting to harsh environments which contain antimicrobial molecules. As a result, organisms such as Acinetobacter baumannii, Mycobacterium abscessus group, and Fusarium spp. have high levels of intrinsic drug resistance. Additionally, they have comparatively large amounts of DNA, giving them a broad genetic repertoire which allows them to survive in hostile environments such as hospital surfaces and equipment. Finally, many MDR-GNBs are genetically promiscuous, taking up DNA which may contain resistance genes from other species or genera of bacteria. This promiscuity has led to a new concept in antimicrobial resistance, the “antimicrobial resistome,” which describes all the antimicrobial-resistant genes in a particular environment.

Rapid expansion in our understanding of molecular biology has greatly enhanced our knowledge of the etiology and epidemiology of infectious diseases. The evolution of molecular diagnostics makes it possible to design a nucleic acid amplification test (NAAT) in a matter of days to detect newly emerging pathogens, such as was done with the 2009 H1N1 influenza A virus. Other applications of NAAT testing allow us to rapidly detect viruses which are not cultivable or were unknown when the 3rd edition of this book was published. DNA sequencing has led to a clearer understanding of how organisms such as members of the Burkholderia cepacia and Mycobacterium chelonae/abscessus complexes are involved in numerous disease processes. Using the tools of direct 16S rRNA gene sequencing, we have greatly improved the etiologic diagnosis of bacterial endocarditis and septic arthritis, leading to an improvement in our understanding of these disease entities.

One of the most significant advances in the study of infectious disease in the past decade has been the Human Microbiome Project. Microbiome studies have shown that many of the microorganisms that are present in our bodies are not cultivable. This observation challenges our basic assumptions of defining a human pathogen based on its ability to grow in vitro or in animal models. The Human Microbiome Project is increasing our understanding of the role of microbial communities in chronic infection, such as those seen in chronic lung disease in cystic fibrosis patients and in chronic wounds of the extremities in diabetics. It is also likely that probing the microbiome will give us greater understanding of such disparate conditions as obesity, inflammatory bowel disease, and perhaps a variety of rheumatologic disorders.

The past decade offered examples of the impact that public health measures can have on the dissemination of infectious diseases following natural disasters. One of the most destructive hurricanes in U.S. history, Katrina, caused massive damage in New Orleans in August 2005 but was responsible for few deaths due to infection and no significant disease outbreaks, despite a complete collapse of that city’s infrastructure and significant damage to medical facilities. This is a testament to the public health interventions that were put in place soon after this catastrophe. This success is in stark contrast to the cholera outbreak that occurred following the magnitude 7 earthquake in Haiti in January 2010. Ironically, Haiti was essentially cholera free until the earthquake. The organism was shown to have been brought to Haiti by UN soldiers from Nepal who were there for humanitarian purposes. This outbreak began several months after the earthquake and the epidemic is still ongoing; as of this writing, more than 8,500 people have died. The reason for this difference is clearly one of resources. Haiti continues to struggle with repairing and upgrading its infrastructure to provide basic sanitation and clean water for its population, while New Orleans and its environs are essentially back to “normal.”

As discouraging as the emergence of MDR-GNBs and the failure to control disease epidemics due to scarce resources might be, much has been accomplished in the past decade in improving the lives of those afflicted with or at risk for infectious disease. Two advances clearly stand out. First, the demonstration that the spread of HIV could be greatly reduced by pre-exposure prophylaxis gives hope that this epidemic that has caused so much suffering can be blunted. Second, new biologics including vaccines and monoclonal antibody preparations are playing an important role in not only infectious diseases but other diseases where there is a malfunctioning of the immune system.

Two vaccines of particular note have been the conjugate 7-valent, now 13-valent, Streptococcus pneumoniae vaccine and a malaria vaccine. The conjugate pneumococcal vaccine has been shown to reduce disseminated disease not only in its target group, young children, but also in the entire population—a clear example of herd immunity. A prototype malaria vaccine has shown success in phase 3 clinical trials and has great promise for reducing malaria disease burden especially among young children, the vaccine’s targeted population.

New monoclonal antibodies show tremendous promise for the treatment of a variety of diseases due to immune dysregulation while at the same time placing individuals at peril for unintended consequences of this therapy. As a result, care providers are faced with “black box” warnings which advise of potentially fatal infectious disease complications of these promising therapies.

The 4th edition of this text provides cases that will illustrate many of these issues. The goal of this edition continues to be to challenge students to develop a working knowledge of the variety of microorganisms that cause infections in humans. This working knowledge is rapidly expanding due to the rapid and increased deployment of NAAT and sequence analysis for detection and identification of microorganisms. As a result, many of the cases have a significant molecular diagnostic component. The “Primer on the Laboratory Diagnosis of Infectious Diseases” has been updated and expanded to reflect the increasing importance of molecular-based assays.

The basic format of this edition is consistent with that of the previous three editions. The cases are presented as “unknowns” and represent actual case presentations of patients we have encountered during our professional duties at two university teaching hospitals. Each case is accompanied by several questions to test knowledge in four broad areas:

 The organism’s characteristics and laboratory diagnosis

 Pathogenesis and clinical characteristics of the infection

 Epidemiology

 Prevention, and in some cases, drug resistance and treatment

This edition features a new section titled “Advanced Cases,” which replaces the section titled “Emerging and Re-Emerging Infectious Diseases.” The types of cases that are seen by our infectious disease consult services and discussed in our weekly infectious disease case management conferences will be found here. These include newly recognized disease agents as well as highly complex cases where the interaction of the immune system and human pathogens can be more closely examined. The Advanced Cases section has all new cases.

This edition contains 74 cases, of which 42 are new. The new cases explore many of the issues described above in this introduction. The 32 cases that have been retained have been updated to reflect the current state of the art as it relates to the organism causing the infection.

The most significant change in the 4th edition is that we bid adieu to one of the authors of the first three editions, Dr. Lynn Smiley, and welcome a new author, Dr. Melissa Miller. This work was Dr. Smiley’s idea, an idea that she helped bring to fruition through three editions. She now passes the mantle to Dr. Miller. Dr. Miller, Director of the Molecular Microbiology Laboratory at UNC Health Care, brings a wealth of knowledge on the molecular aspects of infectious diseases, especially in the fields of virology and antimicrobial resistance. This expertise is essential to produce a contemporary text in medical microbiology and infectious disease. We welcome her!