McCanne Chapter 10: Infectious Disease PDF

For most of human history infection was the primary diseaserelated cause of death including bubonuc/pneumonic plague, Spanish influenza and smallpox. Modern public health initiatives, vaccination programs, and the use of antibiotics have greatly progressed prevention and treatment of infectious disea...

For most of human history infection was the primary diseaserelated cause of death including bubonuc/pneumonic plague, Spanish influenza and smallpox. Modern public health initiatives, vaccination programs, and the use of antibiotics have greatly progressed prevention and treatment of infectious diseases. As a result of these initiatives, naturally occurring smallpox has been eradicated from the globe (the last reported case was in 1975 in Somalia), measles is almost eradicated in the Western Hemisphere, and many diseases, such as tuberculosis and polio, are on the decline. In the United States in 2014, influenza/pneumonia was the eighth and septicemia was the eleventh ranked cause of death in adults, and bacterial sepsis was the seventh leading cause of neonatal deaths.1 However, infectious disease remains a significant threat to life in many parts of the world, particularly in low income countries where prevention is less effective. In these countries 5 of the top 10 causes of death are a ributable to infection: lower respiratory tract infections (#1), HIV/AIDS (#2), diarrheal diseases (#3), malaria (#6), and tuberculosis (#8). Infectious disease remains a significant cause of morbidity and mortality because of the emergence of previously unknown infections, the reemergence and spread of old infections that were thought to be under control, and the development of infectious agents that are resistant to multiple antibiotics. The causes for these occurrences are numerous and include the following: Vast and rapid urbanization in many areas of the world, resulting in a breakdown in public health programs and a more rapid spread of infection Poverty and social inequality War and famine Global travel, allowing more rapid spread of disease from isolated areas to virtually any point around the world in a few hours Human encroachment into wilderness areas, resulting in contact with previously sequestered infectious agents Practice of prescribing antibiotics excessively or not taking antibiotics for a complete course of therapy; or, even when appropriately used, over administration of antibiotics facilitates the emergence of antibioticresistant microorganisms Denial of a problem by governments, allowing infections to spread in an uncontrolled way Diminished use of effective insecticides Increased global warming, allowing insect vectors to spread into and breed in areas that were previously too cool for them Emerging Infections The emergence of previously unknown infections is not a new event in human history. However, the current rate may be unprecedented. Within 1 generation, more than 40 previously unknown infections have arisen. Some of these infections were harbored in animals and spread to humans with significant clinical impacts (e.g., severe acute respiratory syndrome [SARScoronavirus] from bats, Middle East respiratory syndrome [MERS] from dromedary camels).3 These are referred to as zoonotic infections. Zika virus also is an example of a recently emerging infection that has spread globally (see What's New? Zika Virus). Several have extremely high mortality rates of more than 50%, including SARS (in those older than 65 years), Ebola virus, Marburg virus, “mad cow” disease, Nipah virus (up to 75%), and acquired immunodeficiency syndrome (AIDS) (almost 100% in untreated persons). However, most either spread very slowly (e.g., AIDS) or initially appear in relatively isolated areas and are effectively controlled by quarantine (e.g., Ebola virus). Although none of these infections has developed into worldwide scourges, the potential of reversion to more rapidly spreading variants is a concern of public health agencies. In 2015 the World Health Organization (WHO) developed a list of emerging viral diseases that need urgent a ention based on the probability of causing severe epidemics and the lack of medical countermeasures.4 These included MERS, SARScoronavirus, Nipah virus, and hemorrhagic fevers associated with Ebola, Marburg virus, Lassa fever, Rift Valley fever, and Crimean Congo hemorrhagic fever. W h a t 's N e w ? Zika Virus The spread of Zika virus (ZIKV) is the most recent example of an infection emerging from a limited geographical region and rapidly becoming a global health risk of yet unknown impact. Extensive discussions of ZIKV can be found at numerous websites, particularly at those of the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC). ZIKV was discovered in rhesus monkeys in 1947 in the Zika forest of Uganda and in 1948 in local mosquitoes. ZIKV is a member of the Flavivirus family, which includes West Nile virus, dengue virus, yellow fever virus, and tick-borne encephalitis virus. The principal vectors are Aedes aegypti and occasionally A. albopictus. One or both of these mosquitoes are distributed throughout most of the United States.1 The first human cases were found in Uganda and neighboring Tanzania in 1952 and in Nigeria in 1953. ZIKV was progressively detected in western Africa and southern Asia, but human infection was rare. In 2007 the first major outbreak occurred. On the island of Yap in Micronesia about 5000 individuals (73% of the population) were infected.2 Symptoms were relatively mild, and most individuals were asymptomatic. In 2008 the first case in the United States was reported. The number of sexually transmi ed cases has progressively increased. ZIKV has been found in semen, sperm, and vaginal fluid and can be transmi ed during virtually any kind of sexual activity.3 Semen contains infectious virus for up to 6 months after the onset of symptoms and is transmissible at any stage (i.e., before, during, and well after symptoms) or from an individual with a subclinical infection. ZIKV can be transmi ed from mother to child during pregnancy or delivery. Transmission through breast-feeding has not been reported. ZIKV appears to be neurotropic (specifically infects neural tissue). Major fetal complications include miscarriage, fetal death, microcephaly, and ocular disorders. In asymptomatic pregnant women, the risk of microcephaly is relatively low (approximately 1%). In symptomatic women, the incidence is higher (some estimate as high as 29%). Congenital microcephaly presents as a significantly smaller head because of diminished cerebral cortex development and frequently results in early neonatal death.4 Adult complications are relatively few but also neurologic, primarily a postinfection Guillain-Barré syndrome (GBS) that occurs in about 2 of 10,000 individuals.5 GBS is a suspected autoimmune disorder of peripheral nerves leading to peripheral symptoms (e.g., weakness, tingling in the arms or legs, difficulty breathing, complete paralysis, and potentially death because of respiratory failure). The CDC has been closely monitoring ZIKV infections within the United States and U.S. territories. As of September 6 2017, the CDC has reported 231 symptomatic cases in the United States and 554 cases in U.S. territories.6 Very few alternatives are available to limit the spread of ZIKV and a empts to eradicate the vector by destruction of breeding sites are the most effective approach. Prevention includes limiting travel to sites where ZIKV is endemic preventing access of mosquitoes to homes, using insect repellents on exposed skin, and wearing clothing that covers most of the body surfaces in ZIKV-infected areas. References 1. Wikan N, Smith DR. Zika virus: history of a newly emerging arbovirus. Lancet Infect Dis. 2016;16(7):e119– e126. 2. Petersen LR, et al. Zika virus. N Engl J Med. 2016;374(16):1552–1563. 3. Moreira J, et al. Sexually acquired Zika virus: a systemic review. Clin Microbiol Infect. 2017;23(5):296–305. 4. Chibueze EC, et al. Zika virus infection in pregnancy: a systematic review of disease course and complications. Reprod Health. 2017;14(1):28. 5. Lessler J, et al. Review summary: assessing the global threat from Zika virus. Science. 2016;353(6300):663. 6. Centers for Disease Control and Prevention (CDC). 2017 Case counts in the US. [July 20] h ps://www.cdc.gov/zika/reporting/2017-casecounts.html; 2017. At least 20 previously known infections have reemerged including a new strains of cholera, malaria, yellow fever, dengue fever, diptheria, plague, and Marburg virus. The incidence of tuberculosis has risen by almost 33% between the mid-1980s and early 1990s. Although the United States is relatively free of most of these diseases, the effects of global warming and relaxed control of vectors may result in resurgence. West Nile virus, spread by mosquitoes, has spread throughout the continental United States, Canada, and Mexico.5 Many common infections previously controlled by antibiotics or vaccination have reemerged because of antibiotic resistance or secondary to decreased compliance with recommended vaccinations. Examples of these infections include Streptococcus pneumoniae, Staphylococcus aureus, tuberculosis, diarrheal diseases, malaria, meningitis, respiratory tract infections, sexually transmi ed infections (STIs), and human immunodeficiency virus (HIV). Additionally, noncompliance with recommended vaccinations has led to outbreaks of diseases that were once under control (e.g., measles and pertussis). Added to this collage of microbiologic dangers is the rising risk of bioterrorism. Agents such as smallpox, anthrax, and plague are continuing threats to public health and safety. Microorganisms and Humans: a Dynamic Relationship For many microorganisms the human body is a hospitable site in which to grow and flourish because of sufficient nutrients and appropriate conditions of temperature and humidity. Frequently, a symbiotic relationship exists, in which both humans and microorganisms benefit (Box 10.1). These microorganisms make up the normal microbiome—the resident microorganisms found in different parts of the body, including the skin, mouth, gastrointestinal tract, respiratory tract, and genital tract (see Chapter 7). For instance, the normal bacterial microbiome of the human gut is provided with nutrients from ingested food, produces enzymes that facilitate the digestion and use of many of the more complex molecules found in the human diet, produces antibacterial factors (e.g., bacteriocins, colicins) that prevent colonization by pathogenic microorganisms, and produces usable metabolites (e.g., vitamin K, B vitamins). This beneficial homeostasis is normally maintained through the physical integrity of the gut and other mechanisms that sequester these microorganisms on the mucosal surface. Box 10.1 Th e M a n y Re la t io n sh ip s Be t w e e n H u m a n s a n d M icro o rg a n ism s Symbiosis: Benefits only the human; no harm to the microorganism Mutualism: Benefits the human and the microorganism Commensalism: Benefits only the microorganism; no harm to the human Pathogenicity: Benefits the microorganism; harms the human Opportunism: A situation in which benign microorganisms become pathogenic because of decreased human host resistance Microorganisms and Infections Clinical Infectious Disease Microorganisms are generally classified based on different morphologic characteristics and life cycles. However, groups of disease-causing microorganisms share many properties related to clinical disease, processes of infection, and evasion of human protective systems. The clinical process of infection occurs in the following four distinct stages: Incubation period—the period from initial exposure to the infectious agent and the onset of the first symptoms, during which the microorganisms have entered the individual, undergone initial colonization, and begun multiplying, but are at insufficient numbers to cause symptoms; this period may last from several hours to years Prodromal stage—the occurrence of initial symptoms, which are often very mild and include a feeling of discomfort and tiredness Invasion period—the pathogen is multiplying rapidly, invading farther and affecting the tissues at the site of initial colonization as well as other areas; the immune and inflammatory responses have been triggered; symptoms may be specifically related to the pathogen or to the inflammatory response Convalescence—in most instances, the individual's immune and inflammatory systems successfully remove the infectious agent and symptoms decline; alternatively, the disease may be fatal or may enter a latency phase with resolution of symptoms until reactivation at a later time Clinical manifestations of infectious disease vary depending on the pathogen, the organ system affected, and the intensity of the inflammatory response. The disease may be clinical (measurable infection-related symptoms) or subclinical (no apparent symptoms although the individual is infected). Effects of infection may be acute or chronic, secondary to the immune and inflammatory responses, or a direct consequence of toxins or injury to infected cells. The initial symptoms are typically fatigue, malaise, weakness, and loss of concentration. Generalized aching and loss of appetite are common complaints. However, the hallmark of most infectious diseases is fever. Fever is not failure of the body to regulate temperature; rather, body temperature is being regulated to a higher level than normal. The hypothalamus functions as a central thermostat and regulates temperature (see Chapter 16). Pyrogens are agents that can produce fever. Those derived from outside the host are termed exogenous pyrogens and those produced by the individual's inflammatory response are termed endogenous pyrogens. Exogenous pyrogens indirectly affect the hypothalamus through the release of endogenous pyrogens by cells of the host. A number of cytokines have been identified as endogenous pyrogens: interleukin-1 and interleukin-6 (IL-1 and IL-6), interferon (IFN), tumor necrosis factor (TNF), and others (see Fig. 16.8). These cytokines raise the thermoregulatory set point through stimulation of prostaglandin synthesis in both thermoregulatory (brain) and nonthermoregulatory (peripheral) tissue. Fever is considered a beneficial adaptive host-defense response in infection (e.g., killing of temperature-sensitive microorganisms). Several factors influence the capacity of a microorganism to cause disease: Communicability: the ability to spread from one individual to others and cause disease (measles and pertussis spread very easily; HIV is of lower communicability) Immunogenicity: the ability to induce an immune response Infectivity: the ability to invade and multiply in the host Mechanism of action: how the microorganism damages tissue Pathogenicity: the ability to produce disease—success depends on communicability, infectivity, extent of tissue damage, and virulence Portal of entry: the route by which a microorganism infects the host (e.g., direct contact, inhalation, ingestion, or bites of an animal or insect) Toxigenicity: the ability to produce soluble toxins or endotoxins, factors that greatly influence the degree of virulence Virulence: the capacity to cause severe disease, for example, measles virus is of low virulence; rabies virus is highly virulent Infectious diseases also are classified by their prevalence and spread within the community: Endemic: diseases with relatively high but constant rates of infection in a particular population Epidemic: the number of new infections in a particular population greatly exceeds the number usually observed Pandemic: an epidemic that spreads over a large area, such as a continent or worldwide (see Table E 10.1 on Evolve) As a consequence of the relative severity of clinical infection and the ability to successfully treat the infection, some infections are considered relatively minor inconveniencies, such as the common cold, and others have a major impact because of severe morbidity and mortality. In the United States, the Centers for Disease Control and Prevention (CDC) have developed a National Notifiable Diseases Surveillance System.6 An evolving list of notifiable infectious diseases is maintained to monitor, control, and prevent the spread of disease. STIs are among the most common reportable diseases in 2015: Chlamydia (>1.5 million cases), gonorrhea (about 400,000 cases), HIV (>33,000 cases), and syphilis (>23,000 cases). Process of Infection The process of infection includes colonization, invasion, multiplication, and dissemination of pathogenic microorganisms. Many potentially pathogenic microorganisms reside within the normal microbiome without causing severe disease. The symbiotic relationship with the normal flora is maintained by physical barriers (e.g., skin and lining of respiratory and intestinal tracts), the complexity of the microbiome, and inflammatory and immune systems. Microorganisms that may cause infection if the protective barriers or defensive systems are weakened are referred to as opportunistic microorganisms. Physical damage to the intestinal tract during trauma or surgery releases intestinal bacteria into the bloodstream, potentially leading to sepsis, shock, and death. Cuts in the skin may allow normally contained bacteria (e.g., S. aureus) to cause local infections (e.g., abscesses, boils) and invade further and infect various organs. Alterations in the microbiome by antibiotics may allow local overgrowth of opportunistic microorganisms (e.g., Clostridium difficile, Candida albicans). Immune deficiencies may allow invasive systemic infections (e.g., systemic fungal infections) (see Chapter 9). Unlike opportunistic infectious agents, true pathogens have devised means to circumvent the individual's defenses (discussed in Chapters 7 and 8) and cause infection. Infection with these agents is usually dependent on adequate numbers of microorganisms rather than compromise of the host's defenses. The estimated minimum number of microorganisms needed to cause infection (minimum infective dose) varies greatly with the particular pathogen: Vibrio cholerae (103 to 108 microorganisms), norovirus and rotavirus (10–100), Giardia lamblia parasitic diarrhea (10), and Mycobacterium tuberculosis (1 month's duration) Toxoplasmosis of brain, onset at age >1 month Fungal Infections Candidiasis (esophageal, bronchi, tracheal, or pulmonary) Coccidioidomycosis, disseminated or extrapulmonary Cryptococcosis, extrapulmonary Histoplasmosis, disseminated or extrapulmonary Pneumocystis jiroveci (previously known as “Pneumocystis carinii”) pneumonia Bacterial Infections Bacterial infections, multiple or recurrent* Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary Mycobacterium tuberculosis of any site, pulmonary,* disseminated, or extrapulmonary Mycobacterium, other species or unidentified species, disseminated or extrapulmonary Pneumonia, recurrent* Salmonella septicemia, recurrent Viral Infections Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 month Cytomegalovirus retinitis (with loss of vision) Herpes simplex: chronic ulcers (>1 month's duration) or bronchitis, pneumonitis, or esophagitis (onset at age >1 month) Progressive multifocal leukoencephalopathy Varicella-zoster virus (localized or disseminated) Neoplasms Cervical cancer, invasive† Kaposi sarcoma Lymphoma, Burki (or equivalent term) Lymphoma, immunoblastic (or equivalent term) Lymphoma, primary, of brain HIV-Associated Disorders‡ Encephalopathy a ributed to HIV Wasting syndrome a ributed to HIV * Only among children aged