Chapter 26 Infectious Diseases

a LANGE medical book Pathophysiology of Disease An Introduction to Clinical Medicine Seventh Edition

CHAPTER 4 Infectious Diseases

Infection and the Body’s Defense Mechanisms There are several microorganisms that live on and in the human body that do not produce signs of illness Referred to as indigenous flora, these bacteria can also be helpful Pathogens are microorganisms that produce signs of illness

Infection and the Body’s Defense Mechanisms The innate immune system Structural barriers Skin and mucous membranes Inflammatory response The acquired immune system Humoral system Cellular immune system Immunization

Most Frequent and Serious Problems Bacterial Infections Secondary infections, sexually transmitted infections Viral Infections Upper respiratory illnesses Gastroenteritis Cold sores HIV

Most Frequent and Serious Problems Rickettsial Infections Rocky Mountain Spotted Fever Fungal Infections Candida

Most Frequent and Serious Problems Protozoal Infections Malaria Helminth Infections Roundworms

TABLE 4–1 Obtaining a history in the diagnosis of infectious diseases.

FIGURE 4–1 The fundamental relationships involved in the host-agent-environment interaction model. In the host, pathogenetic mechanisms extend from the level of populations (eg, person-to-person transmission) to the level of cellular and molecular processes (eg, genetic susceptibility).

FIGURE 4–2 Phases of the host response to infection FIGURE 4–2 Phases of the host response to infection. During the earliest stage of initial infection, nonspecific mediators (complement, phagocytes) predominate. Adaptive immunity (production of antibody, stimulation of lymphocytes) requires clonal expansion after recognition of specific antigens. Once immunity toward a specific agent is induced, the immune response remains primed so that the response to reinfection is much more rapid.

Symptoms, Signs, and Tests Rapid onset of muscle aches, fatigue, fever, malaise Physical exam Many lesions are characteristic enough to be diagnostic

Symptoms, Signs, and Tests Laboratory testing Culture: most commonly used for bacteria Once the bacteria is identified, it is tested for susceptibility to various antibiotics Gram stains Allow for an “educated guess” about antibiotic coverage while waiting for the organism to be identified

Specific Diseases Staphylococcal Infections S. aureus can develop into Methicillin Resistant S. aureus and cause serious illness in some patients

Specific Diseases Group A Streptococcal Infections Strep A is the most virulent, and common in upper respiratory infections Scarlet fever Necrotizing fascitis

Specific Diseases Streptococcus pneumoniae Common cause of pneumonia Neisseria meningitidis Meningococcal Menigitis

Specific Diseases Haemophilus influenzae Common cause of ear infections and sinusitis Other serious illnesses caused by this bacteria have been eliminated through immunization

Specific Diseases Legionellosis Gram negative bacteria that thrives in water reservoirs and cooling towers A common cause of community acquired pneumonia

Specific Diseases Nonfastidious Gram-Negative Rods Enteric bacteria When these bacteria cause sepsis, they often lead to septic shock with a mortality rate of up to 50%

Specific Diseases Anaerobic Bacteria Bacteria that grow with little oxygen Sexually Transmitted Infections

Specific Diseases Anaerobic Bacteria Bacteria that grow with little oxygen Sexually Transmitted Infections

Specific Diseases Bacterial Infections Mediated by Exotoxins Clostridium Family Tetani (tetanus) Botulinum (botulism) Difficile (entercolitis, not exotoxin mediated) Perfringens (gas gangrene) Diptheria

Specific Diseases Bordetella pertussis (whooping cough) Not as prevalent in young children due to immunization, though resurgence in older children and adults suggests the vaccine needs to be re-administered

Specific Diseases Mycoplasma Disease Common cause of atypical pneumonia Lyme Disease Tick borne disease

Specific Diseases Plague Tularemia Brucellosis Leprosy

Specific Diseases Viral Infections Do not respond to antibiotic therapy and are best treated with supportive mechanisms Few anti-viral medications are available to decrease the duration of illness Immunization has decreased the number of viral infections

Specific Diseases Measles, Mumps, Rubella, and Varicella Young children are immunized against these with one vaccine (MMRV) Smallpox No longer found in the U.S. due to successful vaccination

Specific Diseases Influenza A Causes wide-spread respiratory disease yearly Mononucleosis Epstein-Barr Virus

Specific Diseases Herpes Simplex Type I—mostly oral lesions “cold sores” Type II—genital lesions Human Papillomavirus Some strains associated with the development of cervical cancer

Specific Diseases Cytomegalovirus Human Immunodeficiency Virus Causes AIDS Rickettsial Infections

Specific Diseases Protozoal Disease Malaria Toxoplasmosis Cryptosporidiosis Helminthic Infections Various “worms” Trichinosis

FIGURE 4–3 Commensal bacteria secrete toll-like receptor (TLR) ligands, which bind to TLR on the surface of normal intestinal tissue. This interaction stimulates basal signaling, which protects against cellular injury. Disruption of TLR signaling or antibiotic associated eradication of commensal bacteria result in compromised ability of the intestinal epithelium to withstand injury and repair cell damage. (Redrawn, with permission, from Madara J. Building an intestine—Architectural contributions of commensal bacteria. N Engl J Med. 2004;351:1686.)

FIGURE 4–4 Complement reaction sequence and infections associated with deficiency states. (Redrawn, with permission, from Nairn R. Immunology. In: Brooks GF et al, eds. Jawetz, Melnick, and Adelberg’s Medical Microbiology, 23rd ed. McGraw-Hill, 2004.)

FIGURE 4–5 Pathogenesis of bacterial valve colonization FIGURE 4–5 Pathogenesis of bacterial valve colonization. Viridans group streptococci adhere to fibrin-platelet clots that form at the site of damaged cardiac endothelium (A). The fibrin-adherent streptococci activate monocytes to produce tissue factor activity (TFA) and cytokines (B). These mediators activate the coagulation pathway, resulting in further recruitment of platelets and growth of the vegetation (C). (Redrawn, with permission, from Moreillon P et al. Pathogenesis of streptococcal and staphylococcal endocarditis. Infect Dis Clin North Am. 2002;16:297.)

FIGURE 4–6 Osler node causing pain within pulp of the big toe in a woman hospitalized with acute bacterial endocarditis. (Osler nodes are painful: remember “O” for Ouch and Osler.) Note the multiple painless flat Janeway lesions over the sole of the foot. (Used, with permission, from David A. Kasper, DO, MBA. Originally published in: Chumley H. Bacterial endocarditis. In: Usatine RP et al, eds. The Color Atlas of Family Medicine. McGraw-Hill, 2009:205–9.)

FIGURE 4–7 Pathogenic steps leading to pneumococcal meningitis FIGURE 4–7 Pathogenic steps leading to pneumococcal meningitis. The pneumococcus adheres to and colonizes the nasopharynx. IgA1 protease protects the pneumococcus from host antibody (A). Once in the bloodstream, the bacterial capsule helps the pneumococcus to evade opsonization (B). The pneumococcus accesses the cerebrospinal fluid through receptors on the endothelial surface of the blood-brain barrier (C). (Redrawn, with permission, from Koedel U et al. Pathogenesis and pathophysiology of pneumococcal meningitis. Lancet Infect Dis. 2002;2:731.)

FIGURE 4–8 Pathophysiological alterations leading to neuronal injury during bacterial meningitis. BBB, blood-brain barrier; CBV, cerebral blood volume. (Redrawn, with permission, from Koedel U et al. Pathogenesis and pathophysiology of pneumococcal meningitis. Lancet Infect Dis. 2002;2:731.)

FIGURE 4–9 Pulmonary defense mechanisms FIGURE 4–9 Pulmonary defense mechanisms. Abrupt changes in direction of airflow in the nasal passages can trap potential pathogens. The epiglottis and cough reflex prevent introduction of particulate matter in the lower airway. The ciliated respiratory epithelium propels the overlying mucous layer (right) upward toward the mouth. In the alveoli, cell-mediated immunity, humoral factors, and the inflammatory response defend against lower respiratory tract infections. (C, complement.) (Redrawn, with permission, from Storch GA. Respiratory system. In: Schaechter M et al, eds. Mechanisms of Microbial Disease, 4th ed. Lippincott Williams & Wilkins, 2007.)

FIGURE 4–10 Pathogenesis of Vibrio cholerae and enterotoxigenic E coli (ETEC) in diarrheal disease. V cholerae and ETEC share similar pathogenetic mechanisms in causing diarrheal illness. The bacteria gain entry to the small intestinal lumen through ingestion of contaminated food (left). They elaborate an enterotoxin that is composed of one A subunit and five B subunits. The B subunits bind to the intestinal cell membrane and facilitate entry of part of the A subunit (right). Subsequently, this results in a prolonged activation of adenylyl cyclase and the formation of cyclic adenosine monophosphate (cAMP), which stimulates water and electrolyte secretion by intestinal endothelial cells. (Redrawn, with permission, from Vaughan M. Cholera and cell regulation. Hosp Pract. 1982;17(6):145–52.)

FIGURE 4–11 Pathogenic sequence of the events in septic shock FIGURE 4–11 Pathogenic sequence of the events in septic shock. Activation of macrophages by endotoxin and other proteins leads to release of inflammatory mediators and immune modulation resulting in host tissue damage and, in some cases, death. (Redrawn, with permission, from Horn DL et al. What are the microbial components implicated in the pathogenesis of sepsis? Clin Infect Dis. 2000;31:852.)

TABLE 4–2 Infections associated with common defects in humoral and cellular immune response.

TABLE 4–3 The establishment and outcome of infectious diseases.

TABLE 4–4 Diagnosis of infective endocarditis.

TABLE 4–5 Proportion of cases of bacterial meningitis in the United States by host age, 2003–2007.

TABLE 4–6 Pathogenetic sequence of bacterial neurotropism.

TABLE 4–7 Common etiologic agents of community-acquired pneumonia as determined by severity of illness.

TABLE 4–8 Common risk factors and causes of pneumonia in specific adult hosts.

TABLE 4–9 Approach to GI tract infections.

TABLE 4–10 Escherichia coli in diarrheal disease.

TABLE 4–11 Clinical definition of sepsis.