Home Page for Course BI282

Pathophysiology of Infective Diseases

Course leader: Marguerite A. Neill, M.D.
Co-leader: Josiah Rich, M.D.



OVERVIEW
GASTROINTESTINAL INFECTIONS
HERPESVIRUS DISEASES
CENTRAL NERVOUS SYSTEM INFECTIONS
NONBACTERIAL RESPIRATORY TRACT INFECTIONS
BACTERIAL PNEUMONIA
SEXUALLY TRANSMITTED DISEASES
INFECTIVE ENDOCARDITIS
BACTERIAL SEPSIS
THE MYCOSES
VECTOR-BORNE DISEASES AND ZOONOSES
IMMUNIZATIONS
HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTIONS
URINARY TRACT INFECTIONS
SKIN AND SOFT TISSUE INFECTIONS
BONE AND JOINT INFECTIONS



OVERVIEW OF MICROBIAL PATHOGENESIS AND PATHOGENESIS OF FEVER

We live in a sea of microorganisms and we have evolved systems to prevent being overwhelmed by them. The microbial world is vast and contains organisms of varying size, structure and pathogenicity. The mechanisms by which bacteria, viruses, fungi, parasites, etc., cause disease, infections or infestation depend in one way or another on overwhelming the host defense system(s) of the human. The spectrum of infection depends to a large degree on the integrity of these defenses and severe, often irreversible infections with organisms of relatively low pathogenicity occur when the immune or other defense systems are compromised.



GASTROINTESTINAL INFECTIONS

Key Concepts

  1. Understand how microbial virulence factors contribute to human enteric disease, and influence the clinical features of diarrhea.
  2. Understand the host defense mechanisms which protect against diarrheal pathogens.
  3. Be able to provide an example of one pathogen for each mechanism of diarrhea.
  4. Know the pathogens or patient characteristics which influence treatment decisions.




HERPESVIRUS DISEASES

  1. To provide an overview of herpesvirus infections
  2. To review the pathophysiology of the herpes viruses, especially the concept of latency.
  3. To discuss the clinical manifestations of each of the major members of the herpes family of viruses, including herpes simplex, varicella zoster, cytomegalovirus and Epstein-Barr virus.




CENTRAL NERVOUS SYSTEM INFECTIONS

Key Concepts
  1. Be familiar with general principles and pathophysiology of CNS infections - example by which they will be illustrated is acute bacterial meningitis.
  2. Acute bacterial meningitis.
    1. Definition by anatomic site and clinical manifestations.
    2. Know the major etiologic agents for different ages and host factors.
    3. Know the basic principles of pathogenesis and pathophysiology (colonization, factors leading to systemic invasion of organisms, bacterial and host factors, and resulting inflammations).
    4. Identify the major epidemiologic factor (e.g., colonization, age, crowding).
    5. Recognize the major clinical manifestations and know the tests by which the diagnosis is made.
    6. Understand the principles of therapy.
    7. Know the prognosis (i.e., mortality and morbidity).
    8. Understand the basic principles of prevention (i.e., vaccination).




NONBACTERIAL RESPIRATORY TRACT INFECTIONS

Objectives:
  1. To provide an overview of nonbacterial respiratory infections.
  2. To review the pathophysiology of nonbacterial infections of the nose and throat, larynx and trachea, large bronchi, the bronchioles, and the lungs.
  3. To discuss major non-bacterial respiratory pathogens including rhinovirus, parainfluenza virus, influenza virus, respiratory syncytial virus and Mycoplasma pneumonia.




BACTERIAL PNEUMONIA

Key Concepts
  1. Organisms reach the lower respiratory tract most commonly by aspiration.
  2. Colonization of the oropharynx by potential pathogens often precedes infection.
  3. Host defenses against respiratory pathogens include the epiglottal reflex, cough, polymorphonuclear leukocytes and cellular and humoral immune mechanisms.
  4. Infection of the lower respiratory tract is made more likely by impairment of host defense mechanisms by disease, environmental conditions or iatrogenic factors or by self inflicted abuse.
  5. Treatment is usually empiric and is determined by knowledge of the most likely pathogen in the particular clinical setting.




SEXUALLY TRANSMITTED DISEASES

Objectives:
  1. To understand the factors that underlie the sexual transmission of microbial pathogens and the societal factors related to the increasing dissemination of these organisms.
  2. To understand the epidemiology, pathogenesis and clinical manifestations of the common sexually transmitted diseases including gonorrhea, syphilis, chlamydial infections, genital warts, genital herpes and others.
  3. To understand the principles of treatment, eradication and prevention of sexually transmitted infections.




INFECTIVE ENDOCARDITIS

Key Concepts
  1. Understand the pathophysiology of infective endocarditis and the most common organisms causing these infections.
  2. Recognize the major clinical and laboratory findings of endocarditis, and the diagnostic maneuvers that are necessary to make the diagnosis.
  3. Become familiar with the concepts of endocarditis prophylaxis and principles of antibiotic therapy of established infective endocarditis.




BACTERIAL SEPSIS

Key Concepts
  1. Understand the diverse number of predisposing conditions and variety of microbial pathogens which lead to sepsis.
  2. Review the basic pathophysiology of septic shock.
  3. Describe the clinical features and treatment strategies directed against the mediators of sepsis.




THE MYCOSES

Objectives
  1. Define the differences between bacteria and fungi.
  2. Provide a classification of fungi based on mycologic characteristics and pathogenic potential.
  3. Give an indepth example of the epidemiology pathophysiology and pathology of a major deep fungal pathogen (H. capsulaum).
  4. Briefly introduce the major mycologic, clinical, and pathologic features of the dimorphic fungi, yeasts, molds, and the superficial mycoses of clinical relevance.




VECTOR-BORNE DISEASES AND ZOONOSES

Key Concepts
  1. Review the importance of animal reservoirs, arthropod vectors and changing ecology in the emergence of vector-borne diseases in clinical medicine in the United States.
  2. Focus on vector-borne diseases common in southern New England.
  3. Understand standard diagnostic and therapeutic strategies for vector-borne diseases in the United States.




IMMUNIZATIONS

Key Concepts
  1. Know the difference between active and passive immunization.
  2. Understand the general considerations in active immunizations:
    1. Indications based on disease factors
    2. Different types of vaccines (antigens)
    3. Factors in vaccine schedules (e.g., age of initiation and need for boosters)
    4. Basis of vaccine precautions and contraindications - adverse reactions
    5. Factors in implementation
  3. Know the antigenic component in, indications for, and toxicity of tetanus vaccine
  4. Compare diphtheria vaccine with tetanus vaccine in terms of composition of the vaccine, efficacy, and mechanism of protection.
  5. For Haemophilus influenzae type b immunization, know the antigenic class of the vaccines and the age of initiation of vaccination.
  6. Know the composition, indications and limitations of pneumococcal vaccine.
  7. Know the mechanism of protection and limitations of passive immunization and several examples of its use (e.g., post-exposure prophylaxis against hepatitis A or measles).




HUMAN IMMUNODEFICIENCY VIRUS (HIV) INFECTIONS

Key Concepts
  1. AIDS is due to the depletion and dysfunction of T helper (CD4) lymphocytes and other mononuclear cells because of HIV infection, and it is defined by specific opportunistic infections, neoplasms and immunologic derangements.
  2. HIV is primarily spread via mucosal or parenteral exposure to intimate bodily fluids or blood.
  3. Within a few years after HIV infection few people develop AIDS; after a decade the majority of HIV-infected persons have developed AIDS. Thus, HIV immunosuppression tends to be chronic and progressive.
  4. The current treatments for HIV disease utilize viral reverse transcriptase inhibitors and protease inhibitors which temporarily inhibit, but do not eliminate, HIV replication. Immunomodulators may be added in an effort to augment depleted immunologic function. Survival and quality of life have improved, but the use of these combinations has not yet resulted in viral eradication.
  5. Other AIDS/HIV treatments include the use of prophylactic and therapeutic medications for opportunistic infections, and medications specific for constitutional symptoms, which have also increased survival and improved quality of life.




URINARY TRACT INFECTIONS

Key Concepts
  1. UTIs are classified as "complicated" or "uncomplicated". The former occur inpatients with functionally or anatomically abnormal urinary tracts and the latter in patients in the absence of abnormalities.
  2. UTIs are more common in females overall, but at the extremes of life - neonates and the elderly, males predominate.
  3. E. coli causing UTIs in normal urinary tracts have adhesive factors - "p" pili.
  4. Uncomplicated lower tract infections in females are treated with short course (1-3 days) therapy.
  5. Patients with recurrent, uncomplicated infections (reinfections) should receive TMP/SMX prophylaxis.
  6. Males with uncomplicated UTIs are treated for 7-10 days.
  7. Upper tract infection (pyelonephritis) is treated with 10 to 14 days, usually parenterally.




SKIN AND SOFT TISSUE INFECTIONS

Key Concepts
  1. Understand the major organisms responsible for soft tissue infections and their virulence factors, and become familiar with patients at risk of such infections.
  2. Know the clinical findings typical of important soft tissue infection syndromes, and recognize those which require surgical intervention.
  3. Understand the principles of empiric antibiotic therapy for soft tissue infections.




BONE AND JOINT INFECTIONS

Key Concepts
  1. Know the classification of acute osteomyelitis based on pathogenesis.
    2. Hematogenous osteomyelitis:
    1. Understand the pathogenesis and resulting pathology
    2. Know the major etiologic agents and predisposing factors
    3. Recognize the major clinical manifestations
    4. Be familiar with the diagnostic techniques
    5. Know the principles of therapy
  3. Differentiate other types of osteomyelitis, such as that secondary to a contiguous focus or associated with vascular insufficiency, from acute hematogenous osteomyelitis (e.g., by precipitating factors, age, and duration).
  4. Septic arthritis
    1. Understand the pathogenesis, including predisposing factors
    2. Know the major etiologic agents, according to age and predisposing factors
    3. Recognize the major clinical manifestations
    4. Be familiar with the diagnostic techniques
    5. Know the principles of therapy and prognostic factors
  5. Compare and contrast acute hematogenous osteomyelitis and septic arthritis in terms of pathogenesis, risk factors, etiologic agents, clinical manifestations and principles of therapy


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