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Infectious Diseases 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 Categories • • • • • • • • Prions Viruses Bacteria Fungi Protozoa Helminths Ectoparasites Table 8-1 Classes of Human Pathogens and their Lifestyles 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 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 Routes of Entry of Microbes • Microbes can enter by: – Inhalation – Ingestion – Sexual transmission – Insect or animal bites – Injection 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 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 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 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 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 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 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 How Microorganisms cause Disease • Mechanisms of viral injury • Mechanisms of bacterial injury • Injurious effects of host immunity 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 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 Bacterial Toxins • Endotoxin – LPS of Gram negatives • Exotoxins – Enzymes – Toxins that alter intracellular signaling or regulatory pathways – Neurotoxins – Superantigens 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 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 Spectrum of Inflammatory Responses to Infection • Suppurative (purulent) inflammation • Mononuclear and granulomatous inflammation • Cytopathic-Cytoproliferative reaction • Tissue necrosis • Chronic inflammation and scarring Viral Infections • Acute (transient) infections • Chronic (latent) infections • Chronic productive infections – Hepatitis B Virus • Transforming infections Acute Transient Infections • • • • • Measles Mumps Poliovirus West Nile virus Viral hemorrhagic fevers 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 • Subacute sclerosing panencephalitis (SSPE) • Rash, Koplik spots, Warthin-Finkeldy cells Mumps • Paramyxovirus family • Parotitis, orchitis, pancreatitis, encephalitis Poliovirus • • • • • Enterovirus Fecal-oral route of spread Most infections are asymptomatic Spinal poliomyelitis Bulbar poliomyelitis West Nile Virus • • • • Arbovirus Mosquitos – birds Most infections are asymptomatic Meningitis and/or encephalitis -1/150 clinically apparent cases Viral Hemorrhagic Fevers • Four different RNA viruses • Systemic infections • Animal or insect vector Chronic Latent Infections • • • • ds-DNA viruses Herpes simplex Virus Varicella-Zoster Virus Cytomegalovirus Herpes Simplex Virus • • • • • • • • • • Fever Blisters or cold sores Gingivostomatitis Genital herpes Corneal lesions- keratitis Encephalitis Kaposi varicelliform eruption Eczema herpeticum Esophagitis Bronchopneumonia Hepatitis 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 CMV • Asymptomatic • Mononucleosis-like syndrome • Devastating systemic infection in neonates and immunocompromised hosts • Transmission – – – – – Transplacental Neonatal Saliva Venereal Iatrogenic Transforming Infections • Epstein-Barr Virus – Figure 8-16 – outcome of EBV infection – X-linked lymphoproliferation syndrome (Duncan disease) – Diagnosis • Lymphocytosis with atypical lymphocytes • Postive heterophile antibody reaction (monospot) • Specific antibodies to EBV antigens Bacterial Infections • • • • • • Gram-positive bacteria Gram-negative bacteria Mycobacteria Spirochetes Anaerobic bacteria Obligate intracellular bacteria Gram-Positive • • • • • • Staphococcal infections Streptococal and Enterococcal Diphtheria Listeriosis Anthrax Nocardia infections 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 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 Diphtheria • Skin lesions in infected wounds • Formation of a tough pharyngeal membrane • Toxin-mediated damage to heart, nerves and other organs Listeria • Food-borne illnesses • Pregnant woman, neonates, elderly, and immunosuppressed • Meningitis 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 Nocardia • Similar to molds – branching filaments • Opportunistic infections in immunocompromised hosts Gram-Negative • • • • • • Neisserial Infections Whooping Cough Pseudomonas Infections Plague Chancroid Granuloma Inguinale 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 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 Pseudomonas Infection • Opportunistic gram-negative bacillus • Cystic fibrosis, severe burns, neutropenia • Pili, adherence proteins, endotoxin, exotoxin, , enzymes, iron-containing compounds • Necrotizing pneumonia, vasculitis • Ecthyma gangrenosum • DIC Plague • • • • • Yersinia pestis Gram-negative intracellular bacterium Fleas rodents humans Yop virulon - kills host phagocytes Plague – Bubonic plague – Pneumonic plague – Septicemic plague Chancroid • Soft chancre • Hemophilus ducreyi • Tropics – one of the most common causes of genital ulcers in Africa and Southeast Asia Granuloma Inguinale • • • • • Klebsiella granulomatis Chronic inflammatory disease Tropics Extensive scarring and lymph obstruction Psuedoepitheliomatous hyperplasia Mycobacteria • Tuberculosis • Mycobacterium avium-intracellulare Complex • Leprosy 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 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 Leprosy • Hansen disease • M. leprae • Skin, peripheral nerves –replicates in cool tissues • Disabling deformities • T-helper cell response determines tuberculoid vs lepromatous leprosy Spirochetes • Syphilis • Relapsing fever • Lyme Disease Syphilis • Treponema pallidum • Silver stain, dark-field, immunofluorescence to identify, not Gram stain • Cannot grow in culture • Three stages + congenital – Figure 8-37 • Jarisch-Herxheimer reaction • Pathogenesis – proliferative endarteritis • Serologic testing – Nontreponemal – VDRL and RPR, False – Antitreponemal – fluorescent antibody positives Relapsing Fever • Lice and tick transmitted • Borrelia recurrentis Lyme Disease • • • • Borrelia burgdorferi Ixodes deer tick Three stages – Figure 8-40 Pathogenesis – immune response and accompanying inflammation Anaerobic Bacteria • Abscesses • Clostridial Infections Abscesses caused by Anaerobes • Usually mixed anaerobic and facultative aerobic bacteria • Commensal bacteria from adjacent sites are the usual causes, part of normal flora • Head and neck – Prevotella and Porphyromonas, with S.aureus and S.pyogenes • Fusobacterium necrophorum –Lemierre syndrome • Abdominal – Peptostreptococcus and Clostridium, Bacteriodes fragilis and E. coli • Genital- Prevotella with E. coli and S. Agalactiae Clostridial Infections • Spores, found in soil, do not grow in the oxygen, virulence=toxins • C. tetani – Tetanus, neurotoxin • C. botulinum – neurotoxin, canned foods • C. difficile –overgrowth in intestine after use, pseudomembranous colitis • C. perfringens, C. septicum et al – – – – Gas gangrene Uterine myonecrosis Mild food poisoning Small bowel infection with ischemia or presence of antibiotic neutropenia Obligate Intracellular Bacteria • Chlamydial Infections – C. trachomatis • • • • Serotypes define type of infection Most common sexually transmitted bacterial disease in the world. Urethritis Lymphogranuloma venereum • Rickettsial Infections – – – – Vector-borne typhus and spotted fevers Lice, chiggers, ticks Ehrlichiosis inclusions Severe manifestations are primarily due to vascular leakage secondary to endothelial cell damage Fungal Infections • Yeasts and molds • Mycoses – – – – • • • • Superficial and cutaneous Subcutaneous Endemic Opportunistic Candidiasis Cryptococcosis Aspergillosis Zygomycosis (Mucormycosis) Candidiasis • • • • • Candida – usually a benign commensal Pseudohyphae and budding yeast Vaginitis, diaper rash, thrush Esophagitis –AIDS Invasive – immunosuppressed – – – – Renal abscesses Endocarditis – IV drug users Myocardial abscesses Brain microabscesses. meningitis Crytococcosis • • • • • C. neoformans Meningoencephalitis Opportunistic – high-dose steroids Soil, bird droppings, inhaled Yeast, no hyphae, intense red-staining with Periodic acid-Schiff or mucicarmine, thick gelatinous capsule Aspergillosis • Mold, air-borne, fruiting bodies with septate filaments branching at acute angles • Allergies in other wise healthy people ( allergic bronchopulmonary aspergillosis) • Severe sinusitis, pneumonia, invasive disease in immunosuppressed • Colonizing aspergilliosis • Invasive aspergilliosis • Aflatoxin Zygomycosis (Mucormycosis) • Bread mold • Opportunistic • Neutropenia, steroid use, DM, iron overload, burns, trauma • Rhinocerebral mucormycosis Parasitic Infections • Protozoa – – – – – Malaria Babesiosis – deer ticks, fever and hemolytic anemia Leishmaniasis African Trypanosomiasis – “Sleeping sickness”, tsetse flies Chagas Disease – “kissing bugs” , acute myocarditis or chronic cardiomyopathy • Metazoa – – – – Strongyloidiasis- larvae in soil,autoinfection Tapeworms – undercooked meats or fish Trichinosis – pork, skeletal muscle Schistosomiasis – freshwater snails,hepatic cirrhosis, colon fibrosis, cystitis, squamous cell carcinoma of bladder – Lymphatic filariasis- mosquitos, elephantiasis – Onchocerciasis- black flies, river blindness Malaria • Plasmodium • Anopheles mosquito • Life cycle – sporozoites merozoites trophozoites schizonts gametocytes or more merozoites • Hypnozoites – relapses • Host resistance – Inherited alterations in red cells – Repeated or prolonged exposure • Severe malaria = P. falciparum – Leading cause of death in children under five years of age inn subSaharan Africa – High levels of parasitemia, severe anemia, cerebral symptoms, renal failure, pulmonary edema, death – Ischemia due to poor perfusion causes the main mamifestations of cerebral malaria – High levels of cytokines Leishmaniasis • Sandflies, macrophages • Different species in Old World and New World • Visceral – Hepatosplenomegaly – Pancytopenia, fever, weight loss • Cutaneous – Ulcers • Mucocutaneous – Nasopharyngeal areas, disfiguring • Diffuse cutaneous – Rare form – Single nodule spreads to entire body