Lec 4. Infectious Pathogens of Cardiovascular Diseases, Dr. Blavo - FS - Updated.pdf

Infectious Pathogens of Cardiovascular Diseases COM 5861 LEC 4 Cyril Blavo, D.O., MS, MPH&TM, FACOP Professor of Foundational Sciences, Pediatrics and Public Health Dr. Kiran C. Patel College of Osteopathic Medicine Nova Southeastern University Learning Objectives Infectious Pathogens of Cardiovascu...

Infectious Pathogens of Cardiovascular Diseases COM 5861 LEC 4 Cyril Blavo, D.O., MS, MPH&TM, FACOP Professor of Foundational Sciences, Pediatrics and Public Health Dr. Kiran C. Patel College of Osteopathic Medicine Nova Southeastern University Learning Objectives Infectious Pathogens of Cardiovascular Diseases 1. Describe the taxonomy, morphology, physiology, and pathogenesis the following viruses that cause infectious heart disease: EBV, CMV, and HHV6 2. Describe the taxonomy, morphology, physiology, pathogenesis, the following viruses that cause infectious heart disease: Adenovirus, Coxsackievirus B, HumanParvovirus B19, and Rubella 3. Describe the taxonomy, morphology, physiology, and pathogenesis, of the following bacterial species that cause infectious heart disease: Streptococcus sanguis, Streptococcus oralis, Streptococcus mutans, Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus. 4. Describe the taxonomy, morphology, physiology, and pathogenesis, of the following bacterial species that cause infectious heart disease: Corynebacterium diphtheria, Borrelia burgdorferi, Ehrlichia, Chlamydia pneumoniae, and Neisseria gonorrhea. Infectious Agents Commonly Known to Cause Notable Pathology to the Cardiovascular System Staphylococcus aureus Streptococcus viridans Enterococcus faecalis Streptococcus mutans Streptococcus pneumoniae Human Herpes Virus – 6 Parvovirus B19 Coxsackievirus Cytomegalovirus Adenovirus Streptococcus pyogenes Influenza virus Coronavirus Borrelia burgdoferi Ehrlichia chaffeensis Rubella virus Trypanosoma cruzi Toxoplasma gondii Corynebacterium diphtheria Epstein-Barr Virus Streptococcus sanguis Streptococcus oralis Cardiac Physiopathology Cardiovascular Manifestations of Infectious Diseases: Myocarditis Pericarditis Endocarditis Rheumatic Heart Disease https://www.ebme.co.uk/articles/clinicalengineering/cardiology Cardiovascular Infectious Diseases Infective Endocarditis Endocarditis=Infection/ Inflammation of the Clinical Manifestations: Fever; new Murmur; endocardial surface of the heart, involving 1 or Septic emboli; Petechiae; Splinter hemorrhages more valves. (linear hemorrhages of nail beds); Janeway lesions (painless flat, erythematous lesions on Etiology: Staphylococcus aureus (Acute: most palms and soles); Osler’s nodes (painful raised common); Streptococcus viridans (Subacute: violaceous lesions on finger/toe pads); Roth spots most common). (retinal hemorrhages with pale centers). Associated Etiology: Staphylococcus epidermidis (Prosthetic valves); Enterococcus faecalis (GI/GU procedures); Pseudomonas aeruginosa (Pucture wound); Staphylococcus aureus (injection drug users); Streptococcus gallolyticus (Colon cancer). HACEK organisms (Haemophilus parainfluenzae; Aggregatibacterium aphrophilus; Cardiobacterium hominis; Eikinella corrodens; Kingella kingae)— Cause periodontal disease, Endocarditis and wound infections. Cardiovascular Infectious Diseases Infective Endocarditis Pathogenesis: Bacteremia -> endothelial injury -> formation of vegetations (bacteria; platelets, fibrin) -> valvular regurgitation; thromboembolism. Involves Mitral valve>>Aortic valve.  Acute Endocarditis (large destructive vegetations on previously normal heart valves; Rapid onset; high virulence).  Subacute Endocarditis (smaller vegetations on congenitally abnormal or diseased valves; sequelae of Dental procedures; Gradual onset). Diagnostic Tests: Blood cultures (multiple); Echocardiogram. Diagnosis: Duke criteria= Major (2): Major (1) + Minor (3) OR Minor (5). Major Criteria= Bacteremia, Endocardial; Minor Criteria=Fever, Immune, Vascular, Organism, Risk factors. Management: Vancomycin +/- Gentamycin; Cardiovascular surgery consult. Source: Wikipedia Infective Endocarditis Cardiovascular Infectious Diseases Infective Myocarditis Myocarditis= Infection/inflammation of the myocardium. Infectious Causes: Coxsackievirus B; Adenovirus; Streptococcus pyogenes; Mycoplasma pneumoniae; Trypanosoma cruzi; Toxoplasma gondii; Borrelia burgdorferi; Corynebacterium diphtheriae; Parvovirus B19; HIV; HHV-6; Influenza virus; Coronavirus. Clinical manifestations: Fever; Dyspnea; Chest pain; Flu-like symptoms, Fatigue; Dyspnea; Lower Extremity Edema, Lightheadedness. Complications: Arrythmias; Heart Failure; Cardiomyopathy; Mural Thrombi; Sudden Death. Source: British Heart Foundation Cardiovascular Infectious Diseases Infective Myocarditis Pathogenesis: Inflammation of Myocardium -> myocyte necrosis + fibrosis. Clinical Manifestations: Fever, Chills, Flu-like illness, Chest pain, Palpitations, Syncope. Diagnostic Tests: ECG, Echocardiography, CRP/ESR Treatment: Transvenous pacing. Cardiac transplantation, ECMO Source: Medscape Cardiovascular Infectious Diseases Acute Infectious Pericarditis Pericarditis= Inflammation of the Pericardium Common Causes: Coxsackievirus B; Staphylococcus aureus; Streptococcus viridans; Adenovirus Clinical Manifestation= Sharp pleuritic chest pain, aggravated by supine position and inspiration, alleviated by sitting up and leaning forward; Cough; Pericardial friction rub; EKG changes (Diffuse STsegment elevation +/- PR depression). Complications: Pericardial infusion. Source: RWJ Barnabas Health Cardiovascular Infectious Diseases Acute Infectious Pericarditis Pathogenesis: Viremia/Bacteremia -> infection of pericardium -> inflammation of pericardium -> pericardial effusion -> compromise of cardiac output secondary to cardiac tamponade (fluid in pericardial sac) +/- Pleural effusion. Diagnostic Tests: Blood culture, Echocardiogram, EKG, CXR, Cardiac CT/MRI. Treatment: Analgesics, Colchicine, Corticosteroids, Immunomodulators Radiopedia Pericardial effusion secondary to Pericarditis: “Water bottle sign” Cardiovascular Infectious Diseases Rheumatic Heart Disease Rheumatic Heart Disease=acquired heart disease secondary to systemic immune response to acute rheumatic fever (a complication of GABHS pharyngitis. Most Common Cause: Streptococcus pyogenes (Group A Beta-hemolytic streptococcus: GABHS) Clinical Manifestation: Fever, Swollen, tender, red, very painful joints; Heart murmur (Mitral regurgitation) Rheumatic Heart Disease Source: Australian Institute of Health Cardiovascular Infectious Diseases Rheumatic Heart Disease Pathogenesis: Inflammatory disease (affects heart, joints, skin, brain); Post-GABHD pharyngitis + rheumatic fever; Heart valves: rigidity and deformity of cusps + shortening and fusion of Chordae tendinae -> regurgitation of valve. Mitral valve most commonly involved. Evidence of RHD about 3 weeks post-GABHS Pharyngitis. Myocarditis -> RHD Diagnostic Tests: Echocardiogram. Aschoff bodies in nodules of Heart with RHD. McCallum plaques on valves. Management: IM Benzathine Penicillin G for Acute Rheumatic Fever (Fever; GABHS Pharyngitis; Scarlet Fever; Joint pain). Surgery (Valvuloplasty). Source: Cardiology Research Echocardiogram: Rheumatic Heart Disease Cardiovascular Manifestations of Infectious Diseases Staphylococcus aureus  Characteristics: Bacteria: gram positive facultative anaerobic cocci (in clusters), non-motile, non-sporeforming, coagulase +ve.  Commensal of the skin and nose  Transmission= direct contact; fomites; foodborne, airborne/respiratory droplets.  Cardiovascular Manifestations: Endocarditis Enterococcus faecalis Characteristics: Bacteria. Gram-positive facultative anaerobe cocci, non-motile.  Commensal of the gastrointestinal tract  Transmission: Direct contact with contaminated surgical instruments (GI/GU Procedures), Foodborne.  Virulence Factors:: Adhesins, hemolysin/cytolysin (toxins), biofilm formation. Cardiovascular Manifestations: Endocarditis Cardiovascular Manifestations of Infectious Diseases Streptococcus pyogenes    Characteristics: Bacteria. Gram-positive facultative anaerobic cocci (in chains), sometimes encapsulated, non-motile, nonspore-forming, Normal flora of oropharynx. Causes exudative pharyngitis and scarlet fever. Transmission: Airborne/Respiratory droplet; Person-to Person contact + Fomites. Virulence Factors: M protein, streptolysin O, streptokinase, and pyrogenic exotoxins  Cardiovascular Manifestations: Rheumatic heart Disease  Streptococcus mutans  Characteristics: Gram-positive facultative anaerobic cocci, non-motile.     Normal flora of the Oropharynx, nose, skin Transmission: Direct contact (infected saliva). Pathogenesis: Adheres to tooth surfaces (pits and fissures) biofilms decay (cariogenic) Virulence Factors: metabolize sugars (e.g., sucrose), glucans (form biofilms), acid tolerance (dental caries)  Cardiovascular Manifestations: Endocarditis Cardiovascular Manifestations of Infectious Diseases Streptococcus viridans  Characteristics: Bacteria. Gram-positive facultative anaerobic cocci, non-motile, alphahemolytic. Normal flora of the oropharynx Transmission: dental procedures; Opportunistic. Virulence Factors: Dextran ; plaque-forming biofilms  Cardiovascular Manifestations: Endocarditis; Pericarditis    Staphylococcus epidermidis  Characteristics: Bacteria. Gram-positive facultative anaerobic cocci (in clusters), nonmotile, non-spore-forming ; coagulase -ve, catalase +ve, urease +ve.  Commensal bacterium of the skin  Transmission: Direct Contact; Fomites; Infects prosthetic devices (prosthetic valves)/IV Catheters  Virulence Factors; Polysaccharide intercellular adhesin (PIA); Accumulationassociated protein (Aap)- biofilm formation  Cardiovascular Manifestations: Endocarditis; Cardiovascular Manifestations of Infectious Diseases Adenovirus Characteristics: dsDNA; Naked, icosahedral capsid, linear (capsid fiber-like projections)  Highly contagious; outbreaks in hospitals, summer camps, and daycare  Transmission: respiratory droplets, fecal-oral route.  Pathogenesis: Targets basal cells of the epithelium; blocks synthesis of host cellular DNA  cell death inflammatory response. Cardiovascular Manifestations: Myocarditis; Pericarditis. Human Herpes Virus - 6 Characteristics: Beta-herpesvirus  Transmission by close contact via respiratory secretions, saliva, vertical transmission (infants/toddlers)  Infects and replicates in CD4+ T lymphocytes; Production of pro-inflammatory cytokines  Causes febrile rash in infants: 3 days high fever; fever subsides; followed by a maculopapular erythematous rash= Roseola infantum (Exanthem subitum). Cardiovascular Manifestations: Viral Myocarditis (a rare complication of Roseola; but a common viral cause of myocarditis) Cardiovascular Manifestations of Infectious Diseases Parvovirus B19 Characteristics: ss DNA genome; naked, icosahedral capsid.  Infects younger children  Transmitted by respiratory droplets, blood transfusions, vertical transmission  Targets erythroid progenitor cells; Infects erythroid progenitor cells in the bone marrow, leading to a transient suppression of erythropoiesis (Aplastic Anemia). Causes Erythema infectiosum (“Fifth Disease); Hydrops fetalis. Cardiovascular Manifestations: Myocarditis; Pericarditis Coxsackievirus Characteristics: (+) ss RNA; naked, icosahedral capsid; an enterovirus.  Transmission: Direct Contact, Fecal-oral route  Pathogenesis: virus replicates in oropharynx and intestinal tract lymph nodes  bloodstream CNS meninges, motor neurons  Cytolytic enzymes cause damage to host cells; Causes aphthous stomatitis Hand, Foot and Mouth Disease, and Herpangina, viral sepsis/meningitis. Cardiovascular Manifestations: Myocarditis; Pericarditis. Cardiovascular Manifestations of Infectious Diseases Influenza virus Characteristics: (-)ss RNA virus; enveloped, pleomorphic capsid; Four types (A,B, C, D)  Transmission by Airborne/Respiratory droplet, direct contact  Targets Epithelial cells of the upper and lower respiratory tract  Pathogenesis: Destruction of host respiratory cells inflammation; Virulence: Hemagglutinin (HA) for viral attachment and Neuraminidase (NA) for release of newly formed viral particles from infected cells Cardiovascular Manifestations: Myocarditis; Pericarditis. Cytomegalovirus Characteristics: Beta-herpesvirus  Congenital transmission + transmission via breast milk, sexual contact, saliva  Tissue damage and inflammation: eyes (Chorioretinitis), skin (infant: “Blue-berry muffin rash”); microcephaly.  Microscopy: Cytopathic effects (CPE) like the characteristic “Owl’s eye intranuclear inclusions” Cardiovascular Manifestations: Myocarditis Cardiovascular Manifestations of Infectious Diseases Borrelia burgdorferi  Characteristics: Bacteria; Gram negative spirochete (spiral/”cork-screw shaped” + flagella  Transmission: Bite of infected Ixodes Tick (e.g. Ixodes scapularis)  Borrelia disable complement system through regulation of outer surface proteins, binding complement regulators, and use of tick saliva proteins.  Virulence Factors: OspC, DbpA Lipoproteins Cardiovascular Manifestations: Myocarditis; Pericarditis; Atrio-Ventricular Heart Block; Corynebacterium diphtheriae  Characteristics: Bacteria. Gram-positive aerobic pleomorphic club-shaped, nonmotile.  Transmisssion: Aerosol / Respiratory droplet transmission, direct contact with infected lesions.  Pathogenesis: Adhesion and infiltration in mucosal layers  Releases exotoxininhibits protein synthesis  necrosis in the Pharynx, Cardiac, CNS Cardiovascular Manifestations: Myocarditis Cardiovascular Manifestations of Infectious Diseases Trypanosoma cruzi Characteristics: Flagellated protozoan  Transmission: Bite of Reduviid Bug (Triatoma); Mud-thatch Housing  Pathogenesis: Trypomastigote (Blood) -> Amastigote (Tissue); Organ Involvement: Heart; Muscles; Liver; Spleen; Brain  Virulence: Antioxidant enzymes Cardiovascular Manifestations: Myocarditis; Inflammatory cardiomyopathy. Toxoplasma gondii Characteristics: Coccidian Protozoa (Apicomplexa/sporozoan)  Perinatal infection is common  Transmission: Cysts in undercooked food (pork, sheep); Water; Cat litter; Intermediate Hosts: Farm animals; Cats  Pathogenesis: Ingested Cysts -> Tachyzoites (Trophozoites) -> Intestines -> Tissue cysts -> Eyes; Brain; Congenital CNS Infection; Heart Cardiovascular Manifestations: Myocarditis; Pericarditis; Heart Failure Cardiovascular Manifestations of Infectious Diseases  Streptococcus sanguis: Orophayngeal commensal; May cause acute rheumatic fever and Endocarditis.  Streptococcus oralis: Oral commensal and opportunistic infection; can cause bacteremia and Endocarditis  Erythsipelothrix rhusiopathia: Gram-positive facultative anaerobic bacillus; “Fish handler’s disease”/”Seal finger”; Can cause infection in skin abrasions, arthritis and infective Endocarditis.  Arcanobacterium hemolyticum: Gram-positive facultative anaerobic bacillus. Causes pharyngitis and can cause Endocarditis.  Neisseria gonorrhea: Gram negative diplococci. Rare cardiac manifestation (in disseminated gonorrhea); gonococcal Endocarditis.  Rubella virus: ssRNA virus causes Rubella (German Measles) and Congenital Rubella Syndrome -> Myocarditis; Pericarditis.  Epstein-Barr Virus: HHV-4; Causes infectious mononucleosis and Burkitts Lymphoma-> Can cause Myocarditis; Pericarditis;  Ehrlichia chaffeensis: Gram negative aerobic pleomorphic cocci bacteria; tick-borne (Amblyoma americana=lone star tick). -> Myocarditis (life-threatening)  Chlamydia pneumoniae: Obligate Gram- negative intracellular bacillus. community-acquired pneumonia. -> Myocarditis; Endocarditis; Pericarditis. References/Resources Up-to-Date STAT Pearls Peter, F. et al. Rheumatic heart Disease: Current Status of Diagnosis and Therapy. Cardiovasc, Diag. Ther. 2020. Apr 10(2): 305-315. Kumar, RK. Et al. Contemporary Diagnosis and Management of Rheumatic Heart Disease: Implications for Closing the Gap: A Scientific Statement from the American heart Association. Circulation Vol 142. No 20.