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 infections• Diphtheria• Listeriosis• Anthrax• Nocardia

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 positives– Antitreponemal – fluorescent antibody

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 presence of oxygen, virulence=toxins

• C. tetani – Tetanus, neurotoxin• C. botulinum – neurotoxin, canned foods• C. difficile –overgrowth in intestine after antibiotic use,

pseudomembranous colitis• C. perfringens, C. septicum et al

– Gas gangrene– Uterine myonecrosis– Mild food poisoning– Small bowel infection with ischemia or 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