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Infectious Diseases

Infectious Diseases. General Principles. Categories Special techniques for diagnosing Table 8-2 New and e merging diseases Table 8-3 Agents of bioterrorism Transmission and dissemination of microbes How microorganisms cause disease Immune evasion by microbes

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Infectious Diseases

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  1. Infectious Diseases

  2. General Principles • Categories • Special techniques for diagnosing Table 8-2 • New and emerging diseases Table 8-3 • Agents of bioterrorism • Transmission and dissemination of microbes • How microorganisms cause disease • Immune evasion by microbes • Infections in immunosuppressed hosts • Spectrum of inflammatory responses to infection

  3. Categories • Prions • Viruses • Bacteria • Fungi • Protozoa • Helminths • Ectoparasites • Table 8-1 Classes of Human Pathogens and their Lifestyles

  4. Agents of Bioterrorism • Category A • Highest risk • Readily disseminated or transmitted • High mortality • Major public health impact • Category B • Moderately easy to disseminate • Moderate morbidity, low mortality • Require specific diagnosis • Require disease surveillance • Category C • Emerging pathogens

  5. Transmission and Dissemination of Microbes • Routes of entry • Spread and dissemination • Release of microbes from the body • Sexually transmitted infections • Healthcare-associated infections –”nosocomial” • Host defenses against infection- innate and adaptive immune defenses

  6. Routes of Entry of Microbes • Microbes can enter by: • Inhalation • Ingestion • Sexual transmission • Insect or animal bites • Injection

  7. Skin • Dense, keratinized outer layer is natural barrier to infection • Low pH and presence of fatty acids inhibit growth of microorganisms • Most organisms enter through breaks in the skin

  8. GI tract • Most GI pathogens are transmitted by food or drink contaminated with fecal material • Normal defenses • Acidic gastric secretions • Layer of viscous mucous covering the intestinal epithelium • Lytic pancreatic enzymes and bile detergents • Defensins =mucosal antimicrobial peptides • Normal flora • Secreted IgA antibodies from MALT • Infections via the GI tract our when local defenses are weakened or the organisms develop strategies to overcome these defenses

  9. Respiratory Tract • Large number of organisms are inhaled daily often in dust or aerosol particles • Distance they travel in inversely proportional to their size • Microorganisms that invade the normal healthy respiratory tract have developed specific mechanisms to: • Overcome mucociliary defenses • Avoid destruction by alveolar macrophages

  10. Urogenital Tract • Almost always invaded from the exterior via the urethra • Regular flushing of urine serves as a defense • Short urethra in females, obstruction, reflux • Lactobacilli in vagina

  11. Spread and Dissemination of Microbes • Proliferate locally at the site of infection • Penetrate the epithelial barrier • Spread to distant sites via • Lymphatics • Blood • Nerves • Major manifestations may appear at sites different from the point of entry • Placental-fetal route

  12. Release of Microbes from the Body • Person-to-person transmission • Respiratory • Fecal-oral • Sexual • Blood and blood products • Animal to human • Direct contact • Consumption of animal products • Indirectly through an invertebrate vector

  13. Sexually Transmitted Infections • Infections with one STI-associated organism increases the risk for additional STIs • The microbes that cause STIs can be spread from a pregnant woman to the fetus and cause severe damage to the fetus or child

  14. How Microorganisms cause Disease • Mechanisms of viral injury • Mechanisms of bacterial injury • Injurious effects of host immunity

  15. Mechanisms of Viral Injury • Directly damage cells by entering them and replicating at the host’s expense • Tropism= predilection for viruses to infect certain cells • A major determinant of tissue tropism is the presence of viral receptors on host cells • Direct cytopathic effects • Antiviral immune responses • Transformation of infected cells • Figure 8-5

  16. Mechanisms of Bacterial Injury • Bacterial virulence • Damage to host tissues depends on the ability of the bacteria to: • Adhere to host cells – adhesins, pili • Invade cells and tissues • Deliver toxins • Virulence genes • Pathogenicity islands • Plasmids and bacteriophages • Quorum sensing • Biofilms

  17. Bacterial Toxins • Endotoxin – LPS of Gram negatives • Exotoxins • Enzymes • Toxins that alter intracellular signaling or regulatory pathways • Neurotoxins • Superantigens

  18. Immune Evasion by Microbes • Replication in sites that are inaccessible to the host immune response • Varying the antigens they express: • High mutation rate • Genetic reassortment • Genetic rearrangement • Large diversity of serotypes

  19. Immune Evasion by Microbes • Methods for evading the innate immune defenses • Produce molecules that inhibit innate immunity • Produce factors that decrease recognition of infected cells by CD4+ helper T cells and CD8+ cytotoxic T cells

  20. Spectrum of Inflammatory Responses to Infection • Suppurative (purulent) inflammation • Mononuclear and granulomatous inflammation • Cytopathic-Cytoproliferative reaction • Tissue necrosis • Chronic inflammation and scarring

  21. Viral Infections • Acute (transient) infections • Chronic (latent) infections • Chronic productive infections – Hepatitis B Virus • Transforming infections

  22. Acute Transient Infections • Measles • Mumps • Poliovirus • West Nile virus • Viral hemorrhagic fevers

  23. Measles • Rubeola • Important cause of death in malnourished children • ssRNA virus – paramyxovirus family • Croup, pneumonia, diarrhea with protein-losing enteropathy, keratitis with scarring and blindness, encephalitis, hemorrhagic measles • Subacutesclerosingpanencephalitis (SSPE) • Rash, Koplik spots, Warthin-Finkeldy cells

  24. Mumps • Paramyxovirus family • Parotitis, orchitis, pancreatitis, encephalitis

  25. Poliovirus • Enterovirus • Fecal-oral route of spread • Most infections are asymptomatic • Spinal poliomyelitis • Bulbar poliomyelitis

  26. West Nile Virus • Arbovirus • Mosquitos – birds • Most infections are asymptomatic • Meningitis and/or encephalitis -1/150 clinically apparent cases

  27. Viral Hemorrhagic Fevers • Four different RNA viruses • Systemic infections • Animal or insect vector

  28. Chronic Latent Infections • ds-DNA viruses • Herpes simplex Virus • Varicella-Zoster Virus • Cytomegalovirus

  29. Herpes Simplex Virus • Fever Blisters or cold sores • Gingivostomatitis • Genital herpes • Corneal lesions- keratitis • Encephalitis • Kaposi varicelliform eruption • Eczema herpeticum • Esophagitis • Bronchopneumonia • Hepatitis

  30. Varicella-Zoster • Chickenpox – acute • Crops of lesions from dew drop on a rose petal to vesicle to crusted lesion • Shingles – reactivation of latent • Ramsey hunt syndrome –geniculate nucleus • Dermatomal • Pain as well as rash

  31. CMV • Asymptomatic • Mononucleosis-like syndrome • Devastating systemic infection in neonates and immunocompromised hosts • Transmission • Transplacental • Neonatal • Saliva • Venereal • Iatrogenic

  32. Transforming Infections • Epstein-Barr Virus • Figure 8-16 – outcome of EBV infection • X-linked lymphoproliferation syndrome (Duncan disease) • Diagnosis • Lymphocytosis with atypical lymphocytes • Postiveheterophile antibody reaction (monospot) • Specific antibodies to EBV antigens

  33. Bacterial Infections • Gram-positive bacteria • Gram-negative bacteria • Mycobacteria • Spirochetes • Anaerobic bacteria • Obligate intracellular bacteria

  34. Gram-Positive • Staphococcal infections • Streptococal and Enterococcal infections • Diphtheria • Listeriosis • Anthrax • Nocardia

  35. Staphylococcal Infections • Staph. Aureus • Pyogenic infections • Skin lesions – impetigo, furuncle, carbuncle, hidradenitis, paronchyia, felons, staph scalded skin syndrome (Ritter disease) • Abscesses • Sepsis • Osteomyelitis • Pneumonia • Endocarditis • Multitude of virulence factors • MRSA • Superantigens • Food poisoning • Toxic shock syndrome

  36. Streptococcal Infections • S. pyogenes (Group A) • Pharyngitis, scarlet fever, erysipelas, impetigo, rheumatic heart disease, TSS, glomerulonephritis • S. agalactiae (Group B) • Neonatal sepsis, chorioamnionitis • S. pneumoniae • Lobar pneumonia • S. mutans • Dental decay • Enterococci • Endocarditis and UTIs

  37. Diphtheria • Skin lesions in infected wounds • Formation of a tough pharyngeal membrane • Toxin-mediated damage to heart, nerves and other organs

  38. Listeria • Food-borne illnesses • Pregnant woman, neonates, elderly, and immunosuppressed • Meningitis

  39. Anthrax • Cutaneous • Inhalational • Gastrointestinal • Exposure to animals or animal products such as hides and wool • Spores can be ground into a fine powder making a potent biologic weapon

  40. Nocardia • Similar to molds – branching filaments • Opportunistic infections in immunocompromised hosts

  41. Gram-Negative • Neisserial Infections • Whooping Cough • Pseudomonas Infections • Plague • Chancroid • Granuloma Inguinale

  42. Neisserial Infections • Gram-negative diplococci, coffee bean, chocolate agar • N.meningitidis – meningitis, common colonizer of the oropharynx, complement important in immune response • N. gonorrhoeae – STD, 2nd after chlamydia, urethritis in men, often asymptomatic in women  PID  infertility and ectopic pregnancy • Antigenic variation allows escape from the immune response • Multiple serotypes • Pili proteins and OPA proteins

  43. Whooping Cough • Gram-negative coccobacillius • Bordetella pertussis • Highly contagious • Violent paroxysms of coughing • Inspiratory “whoop” • Laryngotracheobronchitis • Severe cases – bronchial mucosal erosion, hyperemia, copious mucopurulent exudate • Striking peripheral lymphocytosis • Hypercellularity and enlargement of the mucosal lymph follicles and peribronchial lymph nodes • No pneumonia unless superinfected

  44. Pseudomonas Infection • Opportunistic gram-negative bacillus • Cystic fibrosis, severe burns, neutropenia • Pili, adherence proteins, endotoxin, exotoxin, , enzymes, iron-containing compounds • Necrotizing pneumonia, vasculitis • Ecthymagangrenosum • DIC

  45. Plague • Yersinia pestis • Gram-negative intracellular bacterium • Fleas  rodents  humans • Yopvirulon - kills host phagocytes • Plague • Bubonic plague • Pneumonic plague • Septicemic plague

  46. Chancroid • Soft chancre • Hemophilusducreyi • Tropics – one of the most common causes of genital ulcers in Africa and Southeast Asia

  47. Granuloma Inguinale • Klebsiellagranulomatis • Chronic inflammatory disease • Tropics • Extensive scarring and lymph obstruction • Psuedoepitheliomatous hyperplasia

  48. Mycobacteria • Tuberculosis • Mycobacterium avium-intracellulare Complex • Leprosy

  49. Tuberculosis • Mycobacterium tuberculosis • TB flourishes where there is poverty, crowding, and chronic debilitating illness. HIV • Differentiate infection from disease • Most primary TB is asymptomatic • Pathogenesis – Figure 8-27 • Clinical Features – Figure 8-28 • Fever, night sweats, hemoptysis • Ghon complex, Pott disease, intestinal TB – unpasteruerized milk

  50. Mycobacterium avium-intracellulare Complex • MAC • AIDS, CD4+ counts < 60/mm3 • Fever, night sweats, weight loss • Abundant acid-fast organisms within macrophages • Lungs, lymph nodes, liver, spleen

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