Infectious Diseases - Bacteria

November 13, 2017 | Author: miguel cuevas | Category: Tuberculosis, Streptococcus, Infection, Public Health, Meningitis
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PATHOLOGY Infectious Diseases ii:


Dr. Arlene Santos

August 11, 2011


Staphylococcal infections Streptococcal & Enterococcal infections Diphtheria Listeriosis Anthrax (discussed in Bioterrorism) Nocardia

11. Enterotoxin - Another superantigen - Causes food poisoning (Acute self-limited diarrhea) - Stimulates vomiting center in the CNS  ENS  Emesis

Staphylococcal Infections  Gram-positive cocci in clusters (grapelike)  Produce disease by: 1. Multiplication & spread in the tissues 2. Production of toxins & enzymes Note: Cause myriad of skin lesions: boils, carbuncles, furuncles, SSS (Scalded Skin Syndrome), TSS (Toxic Shock Syndrome), abscess formation, endocarditis, food poisoning, osteomyelitis

Toxins and Enzymes of Staphylococci 1.

Catalase - Positive (+) – Bubble formation when H2O2 is added 2. Coagulase - Synonymous with invasive pathogenic potential 3. Hyaluronidase - Hydrolyses hyaluronic acid in the connective tissue  Facilitates spread of infection 4. Staphylokinase - Results in fibrinolysis 5. Proteinases 6. Lipases - Degrades lipids on skin surface - Enables it to produce boils or carbuncles 7. Exotoxins - α-toxin  A hemolysin  Damages platelets  Lethal & dermonecrotic factor  Acts on vascular smooth muscle - β-toxin  Sphingomyelinase  Toxic for many kinds of cells including RBCs - δ-toxin  Detergent-like peptide - γ-Toxin  A hemolysin (Lyses RBC and phagocytic cells) 8. Leukocidin - Lyses phagocytic cells 9. Exfoliative toxin - Causes Scalded Skin syndrome (SSS) /Ritter disease - α & β toxins split the skin by cleaving the protein desmoglein 1  Keeps keratinocytes and epithelial cells intact  Part of desmosomes that hold epidermal cells - This leads to loss in barrier function  Infection - SSS affects granulosa layer which can be distinguished from Toxic Epidermolysis Necrosis (TEN) 10. Toxic Shock Syndrome Toxin (TSS) - The prototype of a superantigen - Associated with fever, shock (hypotension) & multisystem involvement


Fig. Consequences of Staphylococcal Infection

Pathologic Findings 1. Furuncle/boil - Focal suppurative inflammation of skin & subcutaneous tissue - Frequently seen in moist/hairy areas (Face, axillae, groin, legs and submammary folds) - Starts in a single hair follicle  Develops into a growing & deepening abscess 2. Carbuncle - Involves a deeper suppuration, spreading laterally beneath the deep subcutaneous fascia (Upper back and posterior neck)  Burrows superficially to erupt in multiple adjacent skin sinuses 3. Hidradenitis: Chronic suppurative infection of apocrine glands most often in axilla 4. Paronychia: Nail bed infection 5. Felons: Infection on palmar side of fingertips 6. Lung abscess - S. aureus lung infections - Extensive neutrophilic infiltrate within the alveoli - Destruction of the alveoli Note: Staphylococcus infection in general:  Histologically, there is separation and production of purulent exudate  Marked tissue destruction

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3. Streptococcus mutans - Metabolize sucrose to lactic acid  Enamel demineralization - Secret glucans that promote aggregation of bacteria and plaque formation 4. Streptococcus pyogenes - Scarlet fever assoc with pharyngitis

Fig. Lung abscess: Showing neutrophil infiltration with congested vessels

Histopathology of Streptococcal Infections - Neutrophilic infiltration of tissues with edema - Minimal tissue destruction (In contrast to Staph infections) - Abscess formation minimal

Streptococcal and Enterococcal Infections  Gram-positive cocci in pairs or chains Virulent factors & toxins: 1. Capsule – Resist phagocytosis 2. M protein – Antiphagocytic 3. Complement C5a peptidase – Degrades C5a (chemotactic peptide) 4. Pyrogenic toxin – Cause fever & rash in scarlet fever 5. Pneumolysin - Causes tissue damage and reduces complement available for opsonization of bacteria 6. HMW glucans – Promote aggregation of bacteria & plaque formation (Streptococcus mutans – Dental carries) Notes:  Cause myriad of suppurative infection: Skin, oropharynx, lungs, heartvalves  Cause: Post-Strep GN (Glomerulonephritis), Rheumatoid Heart Fever and Erythema nodosa  Can be flesh eating bacteria  Causing rapidly progressive necrolytizing fascisitis Table 1. Common & Important Diseases caused by Streptococci

Infectious Agent Streptococcus pyogenes (Group A strep) Streptococcus agalactiae (Group B strep) Enterococcus faecalis & other enterococci Viridans streptococci (multiple species) Streptococcus pneumoniae (α-hemolytic strep)

Diptheria     

Corynebacterium diptheriae Gram (+) rod Colonizes the oropharynx Transmission: Aerosols or skin shedding Exotoxin (Phage encoded A-B) blocking of protein synthesis via inhibition of EF-2 function essential for mRNA translation to protein  Exotoxin causes necrosis of epithelium  Fibrino-suppurative membrane  Formation of pseudomembranes causes inflammation of bronchus  Tough pharyngeal membrane & toxin-mediated damage in the heart  Bacterial invasion remain localized but may cause several symptoms as a result of entry of soluble exotoxin into the blood. Note: Inclusion of diphtheria toxoid in the childhood vaccine (DPT) does not prevent the colonization of C. diphtheriae but protects immunized children from the lethal effect of the toxin

Disease/s Pharyngitis, Impetigo, Rheumatic fever, Glomerulonephritis, erysipelas, Scarlet fever, TSS

Pathogenesis Corynebacterium diptheriae ↓ Releases an exotoxin ↓ Causes necrosis of epithelium Outpouring of a dense fibrinosuppurative exudate ↓ Coagulation of exudate on ulcerated necrotic surface ↓ A tough, dirty gray to black superficial membrane

Neonatal sepsis & Meningitis Abdominal abscess, Urinary tract infection, Endocarditis S. mutans - Dental caries; Endocarditis, Abscesses Pneumonia, Meningitis, Endocarditis

Pathologic Findings 1. Streptoccocal erysipelas - Cutaneous erythematous swelling - Boarders are hardly demarcated - Exotoxin released from group A & C Streptococci - Rapidly spreading erythematous cutaneous swelling with well-demarcated, serpigenous borders - Pathologic Findings in Streptococcal Infection - Butterfly distribution

Pathologic Findings  Membrane of diptheria lying within a transverse bronchus  Pseudomembranous inflammation of the bronchus  Fibrinosuppurative exudates with aggregates of neutrophils mixed with edema fluid and fibrin  Diptheritic Myocarditis o Interstitial Mononuclear Inflammation o Necrosis of myocardial fibers with mononuclear inflammatory cells in between

2. Streptococcal pharyngitis - Epiglottic swelling and punctuate abscesses of the tonsillar crypts - Minimal tissue destruction - Major antecedent of post-strep GN

Pseudomembranous inflammation of the bronchus

Diptheritic Myocarditis

Fig. Pharynx showing streptococcal infection


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Listeriosis  Listeria monocytogenes – Gram (+) bacillus Table 2. Infection or Diseases Caused by L. monocytogenes

Population at Risk People who consume dairy products, chicken or hotdogs Pregnant women Neonates Neonates; Immunosuppressed individuals

Infection/Disease Food-borne infection Amnionitis Granulomatosis infantiseptica Disseminated listeriosis; Meningitis

Pathologic Findings  Histologic finding: Exudative inflammation (Neutrophilic infiltration of tissues)  Meningitis o Gross finding: Purulent exudate within the leptomeninges o Histological finding: Neutrophils within subarachnoid space & around leptomeningeal vessels o CSF: Gram (+), intracellular bacilli  In neonates & immunosuppressed individuals: Abscesses alternate with grayish or yellow nodules  Neonates with L. monocytogenes sepsis: Red papular rash over extremities & abscesses in the placenta

Nocardia  Nocardiosis  Gram-positive bacilli  Cause opportunistic infections in immunocompromised patients Table 3. Diseases caused by Nocardia species

Infectious Agent Nocardia asteroides

Nocardia brasiliensis

Disease/s Respiratory Infections  Brain abscess (May be mistaken to be Tuberculosis because of similar symptoms) Skin infections

Pathologic Findings  Gram-stain of a sputum: o Smear-beaded o Branched chains o Gram (+) organisms o Found with WBCs  (+) Acid fast along with TB and M. leprae


Neisserial infections Whooping cough Pseudomonas infection Plague – not discussed in lecture but included in ppt Chanchroid (soft chancre) Granuloma inguinale

Neisserial Infections  Neisseria species  Gram (-) diplococci, usually occuring in pairs with or inside WBCs  Neisseria meningitidis – Attach to epithelial cells of the nasopharynx  Neisseria gonorrheae – Attach to epithelial cells of mucous membranes of GUT, eye, rectum & throat  Antigenic variation – Mode to escape the immune response

Determinants of Pathogenicity N.meningitidis 1. Capsular polysaccharides - Inhibit phagocytosis 2. Pili - Enhance attachment to host cells - Adhesion 3. Class 1,2 & 3 proteins - For pore formation in cell wall 4. Class 5 protein (Opa protein) - For adhesion to host cells 5. Lipooligosaccharide - Has endotoxic effects N. gonorrheae nd - 2 leading cause of bacterial STD in States 1. Long Pili - Enhance attachment to CD46 in epithelial cells - Enhance resistance to phagocytosis 2. Protein I (Por protein) - For pore formation 3. Protein II (Opa protein) - For adhesion of gonococci w/in colonies - For attachment to host cells - Associates w/ Por protein in pore formation 6. 4.Lipooligosaccharide - Has endotoxic effects 7. Other proteins: - Lip protein: Heat modifiable protein - Iron-binding protein - IGA 1 protease-inactivates IGA1, a major mucosal Ig Table 4. Infections & Diseases caused by Nesseria sp.

Infectious Agent Neisseria meningitidis

Infection/s Bacterial meningitis Meningococcemia Male – Urethritis Female – Mostly asymptomatic but infection is present in endocervix  Spread to vagina  Fallopian tube  Obliteration  Infertility

Fig. Gram stain showing Nocardia species

 Suppurative inflammation  Granulation tissue formation & fibrosis in the surrounding area  Granulomas do not form Neisseria gonorrheae

Children – Gonococcal ophthalmia neonatorum; during passage in birth canal  conjunctivitis Individuals who lack the complement protein that form the membrane attack complex – Disseminated gonococcal disease (gonococcal arthritis-dermatitis syndrome) Uncommon: Meningitis & Eye infections in adults


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Pathologic Findings: N. meningitidis

Whooping Cough

 Meningococcal Infection - Overwhelming septicemic infection - Rapidly progressing decreased BP  Shock - Spread to subarachnoid space  Meningitis (In children & adults)  Waterhouse–Friderichsen syndrome – Fulminant form of meningococcemia associated with bilateral adrenal hemorrhage  Meningococcal meningitis - Polymorphonuclear infiltration of meninges - Aggregates of polymorpholeukocytes (Neutrophils)

 Bordatella pertussis  Gram (-) coccobacilli  Paroxysmal stage - Cough develops its explosive character & characteristic whoop upon inhalation

Maculopapular rashes in N. meningitides infection

Bilateral adrenal hemorrhage: Waterhouse-Friderischen syndrome

Neutrophilic infiltration around the meninges and its vessels

Gonorrhea  Caused by Neisseria gonorrhea  Adolescent are at high risk  Often asymptomatic, may lead to pelvic inflammatory disease, infertility and ectopic pregnancy  Transmitted by oral, anal or vaginal intercourse  Perinatal transmission  S/S: Urethral infection, vaginal discharge, “Morning drop”  Dx: Gram stain, culture  DNA screening Pathologic Findings

Determinants of Pathogenicity of B. pertussis 1. 2. 3. 4. 8. 9. 10. 11. 12.

Pili Virulence factors Filamentous agglutinin Pertussis toxin Adenyl cyclase toxin Dermonecrotic toxin Hemolysin Tracheal cytotoxin Lipopolysaccharide

Pathogenesis of Whooping Cough B. pertussis ↓ Enters through the respiratory tract ↓ Adhesion & Multiplication on epithelial surface of trachea & bronchi Interference with ciliary action (Paralysis of cilia) ↓ Release of toxins & substances w/c irritate surface cells ↓ Coughing & Lymphocytosis ↓ Focal necrosis of the epithelium Polymorphonuclear infiltration Peribronchial inflammation Interstitial pneumonia ↓ Obstruction of smaller bronchioles by mucus plugs (Mucosal erosion) ↓ Atelectasis Decreased oxygenation of blood ↓ Convulsions in infants w/ whooping cough Note: There is Lymphocytosis not Neutrophilia even though this is a bacterial infection

Pathologic Findings  Bacilli entangled with cilia of the bronchial epithelial cells:

Fig. Urethral discharge in gonorrhoeal infection: “Morning drop”

Acute suppuration ↓ Chronic inflammation Fibrosis

Fig. Bacilli caught by the cilia of bronchial epithelium

Pseudomonas Infection  Pseudomonas aeruginosa  Gram-negative bacillus  Causes opportunistic infections in the following settings: 1. Disruption of skin & mucosa 2. Use of intravenous or urinary catheters 3. Neutropenia (Example: During cancer chemotherapy) Note: Common in hospital acquired infection and is actually the number 1 cause of nosocomial infection


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Determinants of Pathogenicity of P. aeruginosa 1. 2. 3. 4.

Pili Adherence proteins Lipolysaccharide Alginate  Prevents antibodies, antibiotics and complements from acting to Pseudomonas due to biofilm formation 5. Exotoxin A  Inhibits protein synthesis 6. Exoenzyme S 7. G proteins 8. Phospholipase C  Lyse RBC and pulmonary surfactant 9. Elastase  Degrades IgG and ECM proteins 10. Iron-containing compounds  Toxic to endothelial cells  Vascular lesions 11. Mucoid exopolysaccharide called alginate forming a slimy biofilm that protects bacteria from antibodies

Fig. Chancroid Manifestation

Granuloma Inguinale (Donovanosis)  Sexually transmitted disease  Caused by Klebsiella granulomaris (Formerly called Calymmatobacterium donovani)  Coccobacillus  Mode of transmission: Sexual contact

Infections and Diseases caused by P. aeruginosa 1. 2. 3. 4. 5. 6.

Infection of wounds & burns (Source of sepsis) Meningitis Necrotizing pneumonia Otitis externa (Swimmer’s ear) Eye infection Ecthyma gangrenosum (Lesions in patient with skin burns) - In skin burns, it proliferates widely, penetrating deeply into veins and spreads hematogenously - Skin lesions in sepsis - Necrotic & hemorrhagic oval skin lesions

Pathology of Granuloma Inguinale  Caused by Calymmatobacterium donovani  Gross: Painless genital ulcers w/ rolled borders & a friable base  Surrounding granulation tissue soft and sharply demarcated  Single or several  Soft, sharply demarcated areas of granulation tissue that bleeds easily

Pathologic Findings in Necrotizing Pneumonia  Organisms forming a perivascular blue haze in blood vessel walls +Thrombosis + Hemorrhage  Highly suggestive of P. aeruginosa infection Fig. Painless ulcer

Fig. Perivascular blue haze in blood vessels

Note: It is NOT pathognomonic yet highly suggestive of Pseudomonas infection. There is bronchial obstruction in a cystic fibrosis patient due to alginate production.

 Histologically: o Dense dermal inflammatory infiltrate (Histiocytes & plasma cells) with small abscesses o Marked epithelial hyperplasia at the border of ulcer: Pseudoepithelial hyperplasia  Diagnosis: Donovan bodies – Small, round, encapsulated coccobacilli in macrophages or histiocytes

Pathologic Findings  Wright stain of a smear of the lesion-Donovan bodies:

Chancroid         

Caused by Haemophilus ducreyi Sexually transmitted Gram (-) bacillus One of the most common causes of genital ulcers in Africa & Southeast Asia Manifests as a painful genital ulcer in contrast with the genital ulcer of granuloma inguinale which is painless Called chancroid or soft-chancre in contrast to syphilis which have hard chancre Ulcer is not indurated (hardened) and multiple lesions may be present If untreated, inflamed and enlarged nodes (buboes) may erode the overlying skin Dx: Culture

Pathologic Findings  In males – Usually on penis  Chancroid in a female o Starts as an erythematous papule  Ulcer (Has a base covered by shaggy yellow exudate) o Ulcerate in skin with draining exudate o Lesion is on the mons pubis


Fig. Donovan bodies


 Acid fast bacteria due to mycolic acid in cell wall  Obligate aerobes, non-encapsulated, non-spore forming, slowly growing Modes of Transmission  MTb o Aerosol spread: Droplet formation (Coughing or sneezing)  M. bovis o Ingestion (Not common due to pasteurization)  M. avium o Intracellular complex (MAC) widely disseminated infection o AIDS patients – Abundant acid-fast bacilli within macrophages

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Tuberculosis  Caused by M. tuberculosis  An acid-fast bacillus Pathogenesis - Ability to escape killing by macrophages - Type 4 hypersensitivity reaction  Cord factor  Lipoarabinomannan (LAM) – Inhibits macrophage activation  Secretion of TNF  (Fever, tissue damage & weight loss)  Complement activated on the surface of MTb opsonize and facilitate its uptake by MAC Complement receptor

Fig. Macrophages packed with Mycobacteria

 Immunosuppressed individuals without cellular immunity do not form granulomas  No central caseation  Instead, foamy macrophages containing mycobacteria are found Fate of Primary Tuberculosis - Healed and become calcified: 90% - Progression of TB: Spread by contiguity or by erosion into bronchi  Disseminate - Miliary TB – Hematogenous spread of TB throughout the body  Numerous minute yellow-white foci

Secondary TB

Fig. The Natural History & Spectrum of Tuberculosis (fig 8-28 p.369 of Robbins). Study this figure.

Primary Pulmonary TB  0-3 weeks after onset  Pathology of Primary Tuberculosis o Presence of TB granuloma/tubercle in lower lobe o Ghon complex:  Ghon focus (Gray white inflammation) + lymph node  Ranke complex – Ghon complex becomes fibrotic and is the radiologically detectable calcification of the Ghon complex  The focus undergoes caseous necrosis Histopathology of Tuberculosis - A granuloma without central caseation - Acid-fast Stain of Mycobacterium tuberculosis - Presence of TB granuloma in lung parenchyma - Presence of epitheloid cells  If epitheloid cells form a horse-shoe pattern, is called Langhans Giant Cells - At the periphery, lymphocytes are seen

Fig. This is an acid fast stain of Mycobacterium tuberculosis (MTB). Note the red rods--hence the terminology for MTB in histologic sections or smears: Acid fast bacilli


Fig. Lungs of a patient with secondary TB

 > 3 weeks  Post-primary tuberculosis  Reactivation of primary tuberculosis or re-infection in a previously sensitized person  Granuloma in the apex of lung (due to high O2 content)  2 features: Caseation necrosis & Cavities (cavitation)  Resistant to TB: Heart, striated muscle, thyroid gland & pancreas  Yellow/white areas of consolidation in apex  Presence of cavitation Fate of Secondary Tuberculosis - Progressive pulmonary tuberculosis – TB erodes bronchi and vessels  Hemoptysis - Miliary Pulmonary Disease – TB drains into lymphatics to veins and circulate back to the lungs  “Millet seed” appearance - Endobronchial, Endotracheal & laryngeal TB - Systemic Miliary TB – Ehen it reaches systemic arterial system - Isolated Organ TB – May appear in any organ/tissue (Meninges, kidney, adrenals, bones, fallopian tubes& vertebrae) - Lymphadenitis (Occurring in cervical region: Scrofula) - Intestinal TB

Fig. Miliary Tuberculosis of the Spleen: Minute yellow/white foci of consolidation and inflammation

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Diagnosis of Tuberculosis - Clinical history, PE and radiologic findings - AFB smears and culture - Histological findings - PCR – Assay (Advanced rapid and sensitive) - However “culture” – Gold standard (Testing for drug susceptibility and multiple drug resistance)

Pathology of Leprosy - Inflammatory infiltrates in the endoneural & epineural compartments - Cells within the endoneurium contain acid-fast positive lepra bacilli - Presence of hypopigmented maccule - Skin nodules coalesce

Mycobacterium avium-intracellulare Complex MAC  MAC is uncommon except among people with AIDS and low 3 numbers of CD4+ lymphocytes (300 cells/mm3: Usual secondary TB - Patients with
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