Microbial Agents of the Cardiovascular System Infection PDF 2024

Microbial Agents of the Cardiovascular System Infection Charlie A. Clarion, RMT, MD, FPCP, DPCCP Fellow, Philippine College of Physicians Diplomate, Philippine College of Chest Physicians Fellow, MSc in Epidemiology (Clinical Epidemi...

Microbial Agents of the Cardiovascular System Infection Charlie A. Clarion, RMT, MD, FPCP, DPCCP Fellow, Philippine College of Physicians Diplomate, Philippine College of Chest Physicians Fellow, MSc in Epidemiology (Clinical Epidemiology) Introduction Buboes Swollen lymph nodes Lymphangitis Inflamed lymph vessels visible as red streaks under the skin, running along the arm or leg from the site of infection usually in sepsis and septicemia Normal Biota of the Cardiovascular and Lymphatic System Terminologies Bacteremia, Viremia, Fungemia Pseudobacteremia Septicemia Systemic Inflammatory Response Syndrome Sepsis Severe Sepsis Septic Shock Bacteremia Presence of bacteria in the blood as determined by its growth in a blood culture (laboratory finding only) Sources: 1. Focus of infection like pneumonia, urinary tract infection 2. Physical introduction like trauma, catheter insertion, dental prophylaxis Bacteremia Outcome 1. Transient & inconsequential 2. Establishment of distant foci of infection - meningitis, osteomyelitis, endocarditis 3. Progression to sepsis Classification of Bacteremia Site of Origin 1. Primary Bacteremia 2. Secondary Bacteremia 3. Bacteremia of Unknown origin By Duration 1. Transient Bacteremia 2. Intermittent Bacteremia 3. Continuous Bacteremia Pseudobacteremia Positive blood culture as a result of contamination of blood samples during phlebotomy → FALSE Positive – Coagulase-negative staphylococci (CoNS) Significance: Generally, NOT an indication of infection and does NOT require therapy EXCEPT on certain clinical situations Septicemia If the defenses of the cardiovascular and lymphatic systems FAIL, microbes can proliferate in the blood causing an acute illness → SEPTICEMIA – Presence and persistence of microorganisms or their toxins in the blood – Definition is IMPRECISE → NOT suitable in categorizing patients Sepsis (1991 or 2003 Guidelines) Suspected or documented source of infection PLUS Systemic Inflammatory Response Syndrome (SIRS) caused by a focus of infection that releases mediators of inflammation into the circulation > 2 points Sepsis (2016 Criteria) Suspected or documented source of infection PLUS an acute increase in > 2 Sepsis-Related Organ Failure Assessment (SOFA) points 1. Respiratory System 2. Coagulation 3. Hepatic 4. Cardiovascular 5. Central Nervous System 6. Renal Progression of Sepsis Severe Sepsis: – Sepsis plus dysfunction of at least one organ, hypotension, or tissue hypoperfusion Septic Shock: – Low blood pressure can no longer controlled by addition of fluids (refractory hypotension), hence, needing vasopressor therapy Bacteremia to Septic Shock 1. Circulatory collapse (Septic Shock) 2. DIC 3. Multiple organ failure 4. Death Frequently Isolated Organisms from the Blood Gram Negative Bacteria Escherichia coli Klebsiella spp* Proteus spp Pseudomonas spp* Haemophilus influenzae Anaerobes* Bacteroides spp Fungi Candida spp * More common in nosocomial infections More common in community- acquired infections Sepsis Can be caused by either gram positive or gram negative A. Gram-Negative Sepsis Endotoxin: released upon cell lysis → Endotoxic shock – Antibiotics may worsen condition Less than millionth of a mg of endotoxin → cause symptoms of sepsis A. Gram-Positive Sepsis Staphylococci and Streptococci → EXOTOXINS Enterococcus faecium and E faecalis → Healthcare associated infections in wounds and GUT; naturally penicillin resistant, some vancomycin resistant strains Streptococcus agalactiae (Group B streptococcus) → MCC of neonatal sepsis Puerperal Sepsis AKA Puerperal Fever, or Childbirth Fever Etiology: Streptococcus pyogenes (MCC) Begins as infection of uterus due to childbirth or abortion → Peritonitis → Sepsis Modern hygienic practices and antibiotic use → puerperal sepsis is UNCOMMON Diagnosis Culture and Isolation: confirmation & determination of specific etiology How do you collect blood culture? 1. What is the proper technique? 2. When to collect blood sample? 3. How many sites in general? Those who received antibiotics? 4. What is the volume of blood to be collected? Management 1. Antimicrobial therapy – based on results of susceptibility tests – start with broad-spectrum antibiotics before culture results are available, choice is based on: a. Focus of infection b. Age & condition of patient c. Source of infection: hospital vs. community 2. Surgical excision, debridement, draining of identified foci of infection 3. Supportive Measures – fluid replacement, inotropic agents Drotrecogin Alfa (Xigris) Attempt to neutralize the LPS components and inflammation- causing cytokines Anti-inflammatory: decreases IL-6 Antithrombotic: activates protein C, degrades Factor V and VIII → decreases D- dimer Profibrinolytic: decreases PAI-1 activity US FDA Approved Withdraw from the market: Cochrane review failed to show benefit Infection of the Heart Introduction 1. Rheumatic Fever and Rheumatic Heart Disease 2. Infective Endocarditis 3. Myocarditis 4. Pericarditis  CHARACTERISTICS OF MEDICALLY IMPORTANT STREPTOCOCCI Pathogen Habitat Important Clinical Disease (Lancefield) hemolysis Serologic Type of Laboratory Criteria Group A S. pyogenes B Throat, Skin Large colonies (> Pharyngitis, 0.5 mm), PYR* test impetigo, positive, inhibited rheumatic fever, by bacitracin glomerulonephritis B S. agalactiae B Female Hippurate Neonatal sepsis, genital tract hydrolysis, CAMP- Meningitis positive C Streptococcus B Throat Large (> 0.5 mm) Pharyngitis, dysgalactiae colonies pyogenic infections subspecies similar to group A equisimilis; streptococci others *Hydrolysis of L-pyrrolidonyl-2-naphthylamide ("PYR"). Christie, Atkins, Munch-Peterson test CAMP Hemolysis observed on 5% sheep blood agar after overnight incubation  Pathogen Habitat Identification Clinical Disease (Lancefield) hemolysis Serologic Type of D Group Enterococcus A, Colon Growth in presence of bile, Abdominal faecalis and None hydrolyze esculin, growth in abscess, urinary other enterococci 6.5% NaCl, PYR-positive tract infection, endocarditis D Streptococcus None Colon Growth in presence of bile, Endocarditis, bovis (non- hydrolyze esculin, no common blood enterococcus) growth in 6.5% NaCl, isolate in colon degrades starch cancer F (A, C, Streptococcus A, Throat, Small (< 0.5 mm) colony Pyogenic G) and anginosus group B, colon, variants of beta-hemolytic infections, unty- (S anginosus, S None female species. Group A are including brain intermedius, S pable genital bacitracin-resistant and abscesses constellatus, S milleri group) tract PYR-negative. Carbohydrate fermentation patterns  Pathogen Habitat Identification Clinical Disease Serologic Group (Lancefield) hemolysis Type of Viridans A, Mouth, Optochin-resistant. Dental caries (S streptococci None throat, Colonies not soluble in mutans), untypable (many species) colon, bile. Carbohydrate endocarditis, female fermentation patterns abscesses (with genital tract many other bacterial species) None Streptococcus A Throat Susceptible to optochin. Pneumonia, pneumoniae Colonies soluble in bile, meningitis, quellung reaction- endocarditis positive None Pepto- A, Mouth, Obligate anaerobe Abscesses (with streptococcus None colon, multiple other (many species) female bacterial species) genital tract  Rheumatic Fever and Rheumatic Heart Disease Acute Rheumatic Fever An autoimmune inflammatory process that develops as a sequela or complication of streptococcal infection (Streptococcus pyogenes) – Streptococal pharyngitis → (3 weeks: 1-5 weeks) → ARF ARF: Disease of children 5-14 years old RHD: peaks at 25-40 years old Streptococcus pyogenes Respiratory tract & Skin pathogen Gram (+) cocci in pairs or long chains  hemolytic More virulent (strains with capsule) Facultative anaerobe Produces Streptolysin O and DNAse B  Virulence Biologic Effect Factor Capsule Antiphagocytic Lipoteichoic Binds to epithelial cells acid M protein Adhesin; mediates internalization by host cells; degrades complement C3b F protein Mediates adherence to epithelial cells and internalization Pyrogenic Mediate pyrogenecity; enhancement of proteins delayed HPS and susceptibility to endotoxin; cytotoxicity; mitogenicity for T cells; suppression of B cells; production of scarlatiniform rash  Virulence Biologic effect factor Streptolysin S Lyses leukocytes; platelets and erythrocytes; stimulates release of lysosomal enzymes; NOT immunogenic Streptolysin O Lyses leukocytes; platelets and erythrocytes; stimulates release of lysosomal enzymes, immunogenic Streptokinase Lyses blood clots; facilitates spread of bacteria in tissues (used in the treatment of acute MI) DNAse Depolymerizes cell-free DNA in purulent material C5a peptidase Degrades complement C5a Heart Involvement Involves endocardium, myocardium, or pericardium Hallmark: valvular damage → always always affect mitral valve  Joint Involvement: migratory polyarthritis usually affecting large joints Sydenham’s chorea: found mainly in females  Erythema marginatum: pink macules that clear centrally Subcutaneous nodules: painless, small, mobile lumps over bony prominences Diagnosis Serologic Testing – ASO: Streptococcal pharyngitis – Anti-DNAse B: streptococcal skin infection Confirmatory: – Culture Usually negative → Employ Jones Criteria Treatment 1. Treatment of streptococcal infection that led to the disease - Penicillin: DOC 2. Anti-inflammatory drugs a. NSAIDs, salycylates b. Corticosteroids 3. Supportive (CHF) Treatment Primary Prophylaxis - Treatment of Pharyngitis to prevent initial attack of RF -DOC: Penicillin, Erythromycin Secondary Prophylaxis - Prevention of subsequent streptococcal infection in patients who already had RF - Prevention for the long-term consequence of recurrent RF - Penicillin (oral/IM) up to 18th birthday or after 5 years from most recent attack Prognosis - Generally good (only 1% die from fulminant RF) - After initial attack, vulnerability to reactivation of the disease with subsequent pharyngeal infections is increased - Most important consequence: Rheumatic Heart Disease: chronic valvular deformities mitral stenosis- most common Rheumatic Heart Disease Long term sequelae of ARF Usually affects mitral valve – Mitral regurgitation → Mitral stenosis Mitral Stenosis in developing country is RHD until proven otherwise RHD Treatment 1. Infective Endocarditis Prophylaxis 2. Valve Replacement Surgery Infective Endocarditis Introduction Attachment of blood borne bacteria to heart valves, covered with platelets & fibrin (shield from phagocytes & complement) →Vegetation: prototypic lesion of IE Pathophysiology Associated with cardiac valve abnormality like RHD Classification Acute Bacterial Endocarditis – 1-2 weeks – Toxic – Etiology: S aureus, Pneumococcus, S pyogenes, Enterococcus Subacute Bacterial Endocarditis – >2 weeks – Insidious – Etiology: Viridans streptococcus, Enterococcus Etiologic Agents Risk Factors An artificial (prosthetic) heart valve Heart valves damaged (scarred) by conditions such as rheumatic fever Congenital heart or heart valve defects Mitral valve prolapse with a murmur Hypertrophic cardiomyopathy A family history of endocarditis Work-Up 2DEcho – TTE, TEE Blood Culture – 3 sets, 2 sites each set, one hour apart PCR – Brucella, Bartonella, Legionella, Chlamydia psittaci, and C. burnetii. Management Antibiotic Therapy Surgery Supportive for acute decompensated heart failure Outcome Heart Failure Arrhythmia Septic embolization Sepsis Myocarditis Introcduction Definition: inflammation of the heart that result from multiple causes but is most commonly attributed to infective agents that can injure the myocardium through direct invasion, production of cardiotoxic substances, or chronic inflammation with or without persistent infection Manifestation Typical viral syndrome occurs with cardiac symptoms such as shortness of breath and chest pain which can result pericarditis or myocarditis Signs and symptoms of heart failure Chest pain → associated with pericarditis or MI Reduced left ventricular ejection fraction or regional wall motion abnormality → Pulmonary or systemic emboli from intracardiac thrombus Fulminant myocarditis → cardiogenic shock → death Infective Myocarditis Viruses – Picornavirus (enterovirus, coxsackie virus, echovirus, poliovirus), adenovirus, vaccinia, herpesviruses (VZV, CMV, EBV, and HHV6), HIV, Mumps virus, RSV, arbovirus (dengue virus and yellow fever), HCV – Therapy: no specific therapy HIV: antiretroviral therapy Parasite – Chagas’ disease (T. cruzi): most common infective cause of cardiomyopathy – Toxoplasmosis, Trichinellosis Infective Myocarditis Bacteria – Diphtheria, clostridium, chlamydophila, legionella, meningococcus, mycoplasma, streptococcal, brucellosis, psittacosis, TB, whipple’s disease, Borrelia burgdorferi Fungal – Aspergillosis, actinomycosis, blastomycosis, mucormycosis Diagnosis Laboratory evaluation – ECG, 2DEcho, Troponin and CK-MB – Cardiac MRI – Endomyocardial biopsy Not often indicated as initial evaluation unless ventricular tachyarrhythia suggests possible etiologies of sarcoidosis or giant cell myocarditis Dallas Criteria for Myocarditis – Lymphocytic infiltrate with evidence of myocyte necrosis – Negative in 90-90% of patients with clinical myocarditis » Sampling error or early resolution of lymphocytic infiltrates Normal Myocardium Myocarditis Management Viral Myocarditis: supportive care Bacterial: Antibiotic therapy Address arrhythmia Address heart failure symptoms Pericarditis Introduction Inflammation of the pericardium with or without involvement of myocardium  MICROSCOPIC GROSS Manifestation Four Principal Diagnostic Features: 1. Chest pain: Severe, retrosternal and left precordial, referred to neck, arms, and left shoulder + rise of CKMB and Trop I [CONFUSED WITH AMI] – often intensifies upon lying down or inhaling deeply, sitting up and leaning forward can often ease the pain 2. Pericardial friction rub: high pitched, rasping, scratching, or grating sound heard at left sternal border that disappear within hours and reappear the next day 3. Typical ECG findings 4. Pericardial effusion Viral or Idiopathic Form of Acute Pericarditis Coxsackie A or B, Echovirus, Mumps, Herpes simplex, Chickenpox, Adenovirus, CMV, EBV, HIV HIV/AIDS → pericardial effusion usually due to mycobacterial infection or neoplasm usu lymphoma Management (Viral) Viral: – No specific therapy – Bed rest and anti-inflammatory aspirin, ibuprofen, Indomethacin along with gastric protectant colchicine steroids – Avoid anticoagulants → bleeding into pericardial space → tamponade Management Bacterial – Antibiotics Tuberculous – Anti-TB meds Management Pericardial Effusion – Minimal: Observe – Massive or with tamponade: pericardiocentesis, pericardial window creation Chronic Constrictive Pericarditis Few symptoms or no symptoms at all Usually detected by finding enlarged cardiac silhouette Common cause: Mycobacterium tuberculosis Chronic Constrictive Pericarditis Results when healing of an acute fibrinous or serofibrinous pericarditis or the resorption of a chronic pericardial effusion is followed by obliteration of the pericardial cavity with formation of a granulation tissue → contracts and forms firm scar → calcified → encases the heart and prevents filling of ventricles Diagnosis CXR: normal or slightly enlarged heart, pericardial calcification (TB pericarditis) 2DEcho: pericardial thickening, MRI and CT scan: more accurate than 2DEcho Tuberculous Pericardial Disease Pericardial biopsy: – Granuloma with caseation Management Anti-TB medications Pericardial resection – Operative mortality: 5-10%, highest mortality when already severe, hence, surgery should be done relatively early in the course Zoonotic Bacterial Infections Zoonotic Infection Infection transmitted from animals to humans Disease Pathogen Brucellosis (Undulant Fever) Brucella spp Anthrax Bacillus anthracis Tularemia Francisella tularensis Animal Bite Pasteurella multocida Rat-Bite Fever Streptobacillus moniliformis Spirillum minus Cat-scratch Disease Bartonella henselae Leptospirosis Leptospira interrogans Brucella spp Introduction Brucellosis: an infectious disease that spreads from animals to people — most often via unpasteurized milk, cheese and other dairy products – World’s MC bacterial zoonosis Non-fatal among humans but persist in reticuloendothelial system: adept in evading the immune system Biology Small, aerobic, gram negative cocco-bacilli Laboratory handling: easily become airborne → dangerous to handle Agent of bioterrorism Species Brucella melitensis: – Goats, sheep, camels – Cause of most human cases now Brucella abortus: – Cattle, also in camels, bison Brucella suis: – Pigs/swine among abattoir workers Mode of Transmission Ingestion of raw unpasteurized infected milk/meat Inhalation (Aerosols ) Introduction into skin abrasions (Percutaneous) or contact with conjunctival surfaces Manifestations Initial symptoms can include: Recurrent fever Arthritis Undulant Fever Swelling of the testicle and sweats scrotum area Swelling of the heart malaise (endocarditis) anorexia Neurologic symptoms (in up to 5% of all cases) headache Chronic fatigue pain in muscles, joint, and/or Depression back Swelling of the liver and/or spleen fatigue Diagnosis Exams and Tests – Blood culture – Bone marrow culture – Clean catch urine culture – CSF culture Serology for brucellosis antigen Treatment DOC Streptomycin (2-3 weeks) PLUS doxycycline (6 weeks) Alternative Rifampin PLUS doxycycline Pregnant, Children High dose cotrimoxazole Possible Complications Bone and joint sores (lesions) Encephalitis Infective endocarditis Meningitis Bacillus anthracis Introduction Isolated by Robert Koch in 1877 Disease: Anthrax or Woolsorter’s Disease or Malignant Pustule Anthrax: Greek meaning coal Naturally occurring in soil – Pathogen of grazing herbivores like sheep, goat, cattle Common in agricultural regions: Central and South America, Africa, Middle East Biology Gram positive, obligate aerobic bacillus Encapsulated, non-motile Spore-forming – Survive up to 60 years 1. Indirect Contact 2. Inhalation 3. Direct Contact Antigenic Structure 1. Capsule polypeptide – D-glutamic acid – Poorly immunogenic → Stimulates antibody formation but not protective 2. Polysaccharide somatic antigen 3. Complex protein toxin Virulence Factor 1. Polypeptide capsule: glutamic acid – anti-phagocytic – no immunologic response unlike polysaccharide 2. Exotoxin: responsible for the development of lethal effects; SYNERGISTIC EFFECT A. Protective Antigen: Binds to cell receptor B. Edema Factor: adenylate cyclase activity → edema C. Lethal Factor: targets and kills macrophages 1. Cutaneous Anthrax MC form of anthrax (90%) Transmission: spores enter host through abraded skin → germinate 48-72 hours → formation of papule that darkens → vesicle that ruptures → painless, crater-like ulcer → ESCHAR (heals without scarring) 20% of cutaneous form → bloodstream and disseminate – With antibiotics, death is rare 2. Gastrointestinal Anthrax Second most common form Transmission: ingestion of undercooked food containing endospores → germinate → enter pre-existing intestinal mucosal lesions → disseminate to lymphatics Manifestation: fever, nausea, abdominal pain, bloody stools, septicemia – Ulcer from mouth and throat to intestines (mainly) 3. Pulmonary (Inhalation Anthrax) Most dangerous form Woolsorter’s Disease Transmission: inhalation of spores from contaminated animal products Macrophages ingest spores → germination of spores → sepsis → death within 24 hours if no antibiotics given Manifestation: influenza-like which develops to severe fatal pneumonia Mortality rate: almost 100% if no antibiotics Mediastinal Widening and/or Pleural Effusion Diagnosis Specimen: pustule, sputum, blood Presumptive Diagnosis: gram stain, and fluorescent-antibody stain Penicillin containing medium: String of Pearls Reaction Antibody detection: gel diffusion, microhemagglutination, ELISA Treatment Drug of Choices – Nonbioterrorist anthrax: Penicillin Clindamycin: added for its anti-exotoxin effect – Bioterrorist anthrax: Ciprofloxacin or Doxycycline Postexposure prophylaxis: ciprofloxacin, levofloxacin, doxycycline Raxibacumab Human IgG1 gamma monoclonal antibody directed at the protective antigen of Bacillus anthracis Prevention Vaccination – Humans: cell-free vaccine prepared from the protective antigen of B. anthracis, preventing entry of other toxins Series of 6 injections over 18 months, then annual booster dose – Animals: avirulent, non-encapsulated strain of B. anthracis Prevention Environmental Control – Infected animal carcasses should be incinerated or buried in deep pits – *Application of lye or quick lime: NOT recommended because it prolongs survival of spores Francisella tularensis Introduction First isolated in 1911 → outbreak of ground squirrels in Tulare County, California Disease: Tularemia or Rabbit Fever Biology Small, aerobic, gram-negative coccobacillus Non-motile, non-spore forming Obligate intracellular – Dependent on invasion of host cells in vivo→ multiply and cause disease Biology Reservoir Animals – Lagamorphs (Rabbits, Hares), Terrestrial rodents (Voles, Meadow mice), Acquatic rodents (Muskrats, beavers) Vectors: – Ticks, Fleas, Deer fly, Mosquito Transmission: – Arthropod bite – Direct exposure to contaminated materials (Skin, Mouth, Lungs, Eyes) – *No documented person-to-person transmission Francisella Pathogenicity Island (FPI) gene Manifestations Manifestations Manifestations Manifestations Widened Mediastinum on CXR Influenza-like disease → dyspnea, hemoptysis, sepsis → shock Diagnosis Challenging: diverse clinical syndromes Culture: – Blood, leading margin of lesions – Slow growing (36-48 hours incubation; Fastidious organism requiring amino acid cysteine for optimal growth Buffered Charcoal Yeast Extract Agar Chocolate Agar with Cysteine Modified Thayer Martin Cysteine Heart Agar Management Streptomycin: DOC Gentamicin: acceptable alternative Prevention Insect repellants Wearing of long pants, long sleeves, long socks Manual removal of ticks Wearing of gloves NO VACCINE AVAILABLE Leptospira interrogans Introduction Worldwide distribution in subtropics and tropics like Philippines Reservoir: Rodents (kidney) Biology Tightly coiled, thin, flexible spirochetes, 6-20 micra in length and 0.1 micron in diameter, one or both ends are hooked Ultrastructure – Leptospira consists of a helicoidal protoplasmic cylinder, 2 axial filaments, and an outer envelope Obligate aerobe, Oxidase (+), Catalase (+) Stained by silver stain Virulence Mechanism Reduced phagocytosis Production of hemolysins and endotoxins Cell-mediated sensitivity to leptospiral antigen by the host Diagnosis (Clinical) 1. Acute febrile illness at least 2 days 2. Either residing in a flooded area OR high risk exposure such as wading in floods and contaminated water, contact with animal fluids, swimming in flood water or ingestion of contaminated water (+/- cuts or wounds) 3. At least two of the following: myalgia, calf tenderness, conjunctival suffusion, chills, abdominal pain, headache, jaundice, and oliguria. Classification of Leptospirosis MILD LEPTOSPIROSIS MODERATE-SEVERE Stable vital signs Unstable vital signs Anicteric sclerae Jaundice/icteric slcerae Good urine output Nausea, vomiting and diarrhea (-) meningismus/meningeal Oliguria/anuria irritation Meningismus/meningeal (-) sepsis/shock irritation (-) difficulty of beathing Sepsis/septic shock (-) jaundice Altered mental status DOB/Hemoptysis OUTPATIENT SETTING HEALTHCARE/HOSPITAL SETTING Manifestations 1. Subclinical (Asymptomatic) Disease - positivity to antibodies, no sign/symptom - thru serological survey of veterinarians 2. Anicteric Leptospirosis Initial stage (IP=7-12 days) - non specific flu-like symptoms Secondary stage (duration: few days up to 1 month) - serum positivity for antibody & immune complex - severe headache, nausea and vomiting, myalgia - splenomegaly, hepatomegaly, meningitis Manifestations 3. Icteric Leptospirosis (Weil’s Syndrome) - most severe form of the disease - disseminated endothelial damage & vasculitis - impaired renal & hepatic fxn, internal hemorrhages, meningitis, cardiovascular collapse & shock - hepatomegaly (25%) Diagnosis (Laboratory) Direct Detection Methods – Culture and Isolation: Gold standard Media: Fletcher’s semisolid, Stuart liquid, or Ellinghausen-McCullough- Johnson-Harris semisolid media Time consuming, labor-intensive, low yield First week: Blood, CSF, Dialysate Second to Fourth: Urine – PCR High cost, need trained personnel Diagnosis (Laboratory) Indirect Detection – Micro-agglutination Test (MAT) Highly sensitive and specific Time consuming; hazardous Confirmatory 1. Four-fold rise of titer (2 samples: acute and convalescent) 2. Single titer 1:1600 (endemic areas) – Specific IgM Rapid Diagnostic Test – Non-specific Rapid Diagnostic Test Management Complications Renal Failure Pulmonary Hemorrhage Weils Disease Jarisch-Herxheimer Reaction Pasteurella multocida Introduction Transmission: animal bite usu feline and canines Isolated by Louis Pasteur in 1880 among birds suffering from cholera Residence of respiratory and oral cavities of mammals and birds Species Pasteurella multocida with three subspecies – P multocida multocida: most frequent isolated species Five serogroups (A, B, D, E, and F) defined by capsular antigens – P multocida septica, P multocida gallicida Pasteurella canis: assoc with dogs Pasteurella stomatis, Pasteurella dagmatis: assoc with dogs and cats Biology Gram negative, coccobacilli Non-motile, facultative anaerobic Encapsulated BIPOLAR STAINING: safety pin appearance when poles of the cells are more intensely stained with Giemsa or Methylene blue Diagnosis Culture: – Sheep blood agar Almost the same morphology with Haemophilus except the presence of narrow green-to- brown halo around the colony after 48 hours MUSTY odor Main Virulence Factor Capsule: Anti-phagocytic, mimic the hosts cell antigen Manifestations Cutaneous form: MC form Others: Immunocompromised – Systemic (septicemia, arthritis, endocarditis, osteomyelitis, meningitis) – Pneumonic form Management DOC: – Amoxicillin-clavulanic acid – Ampicillin-sulbactam Tetanus prophylaxis Rabies prophylaxis Rat-Bite Fever Introduction Two Bacteria 1. Streptobacillus moniliformis Streptobacillary rat-bite fever Haverhill fever (organism is ingested) 2. Spirillum minus Spirillar fever or Sodoku 1. Streptobacillus moniliformis First isolated in 1914 from a rat-bitten patient Moniliformis means necklace Filamentous, non-branching, highly- pleomorphic bacilli – With lateral bulbar swelling Non-motile, non-encapsulated, facultative anaerobe 1. Streptobacillus moniliformis Culture – Inhibited by sodium polyanethol sulfonate: anticoagulant present in commercial aerobic blood culture bottle – Media: Tryptase soy agar or broth containing 10-20% blood, serum or ascites fluid PUFF BALL APPEARANCE 1. Streptobacillus moniliformis Manifestation – Rat-Bite Fever – Haverhill fever Fever, chills, muscle & joint pains followed by a rash on the extremities – Complications: Endocarditis, myocarditis, pericarditis, meningitis, pneumonia, abscess Management Drug of Choice – Penicillin If left untreated → 10% mortality 2. Spirillum minus Transmission: bite of wild rodents Short Gram-negative spirals with amphitrichous flagella Facultative anaerobe 2. Spirillum minus Culture – Difficult to culture Dark-field microscopy taken from lesions 2. Spirillum minus Manifestations – Spirillar fever, Sodoku fever (Asia) – Complications: endocarditis, meningitis, myocarditis, nephritis 2. Spirillum minus Management – DOC: Penicillin – Alternative Drug: Tetracycline If left untreated → FATAL Cat-Scratch Disease Introduction Etiology: Bartonella henselae Reservoir Host: Cats A benign, self-limited illness manifested by – fever and lymphadenopathy: develop 2 weeks after contact with a cat (scratch, lick, bite (flea bite) Biology Gram negative, aerobic, facultative intracellular, pleomorphic bacteria Targeting RBC Present mainly in the walls of capillaries near follicular hyperplasia or microabscesses Transmission Primary MOT: cat scratch Others (?) – Cat bite – Flea bite Flea: required to maintain infection among cats – Bacteria multiply in the digestive system of cat flea Manifestations Low-grade fever, headache, sore throat, conjunctivitis Regional lymphadenopathy Skin lesions occur in crops, generally nodular, red or purple, can ulcerate Easily bleed with trauma Severe among HIV patients: Bacillary angiomatosis Diagnosis Tissue sections stained with Warthin-Starry Silver Impregnation stain May also be detected by immunofluorescent stains Enzyme immunoassay Management Self-limited Treatment : – supportive + antibiotics (Macrolide or Doxycycline; Aminoglycosides) Aspiration of pus/surgical removal may ameliorate symptoms Vector-Transmitted Diseases Yersinia pestis Introduction 1894, Alexandre Yersin first describe plague bacillus Known in the Middle Ages as Black Death dark blue areas of skin caused by hemorrhage Xenopsylla cheopis: major vector (flea) but NOT always necessary for transmission Rattus rattus: black rat, responsible for urban outbreaks Biology Gram negative , non-motile, coccobacillus Facultative anaerobe Catalase positive Grows best at 28°C Facultative intracellular organism 1. Flea Bite 2. Inhalation 1. Bubonic Plague MC form: 80-95% cases today Lymph node enlargement Mortality rate if untreated: 50-75% in less than a week Bubo: hallmark of bubonic plague Location of Buboes is a strong indicator of inoculation site 2. Septicemic Plague Once bubo ruptures → organisms disseminate hematogenously → septic shock → MODS, DIC → gangrene of extremities [BLACK DEATH] *Primary septicemic plague 3. Pneumonic Plague Blood carries the bacteria to the lungs → hemoptysis If unrecognized for 12-15 hours from onset of fever, rarely controlled → mortality rate is almost 100% Diagnosis Culture and Isolation – Blood: one bottle incubated at 22- 28C – Sputum, bronchial wash, tracheal aspirate – Aspirate from buboes Sheep Blood Agar – Flattened edges with raised center: Fried egg appearance Management Post-Exposure Prophylaxis – 7 days course of oral doxycyline or ciprofloxacin Treatment – Streptomycin – Chloramphenicol – Gentamicin – Quinolones Previous infection confers immunity Vaccine for field workers in endemic area Borrelia burgdorferi Introduction 1975, among young people near the city of Lyme, Connecticut → Lyme Disease Ixodes Tick: Vector Field mice: Reservoir host; nymph stage feeds on Deer: Dead-end host; Adult ticks feed and mate on them → Maintain disease Biology Highly flexible, less tightly coiled spirochete Gram negative Manifestations Early Infection – Stage 1: localized; erythema marginatum at bite site, LAD – Stage 2: early disseminated; cardiac pathology, splenomegaly, migratory joint and bone pain Manifestations Late infection – Stage 3: late manifestations: cardiac, neurologic, musculoskeletal like arthritis Diagnosis Culture and Isolation – Media: Barbour-Stoenner-Kelly Medium supplemented with serum Serologic Testing Management Antimicrobials – Early Stage: doxycycline and amoxicillin – Late Stage: ceftriaxone Cardiac manifestation like complete heart block – Pacemaker Typhus Introduction Various typhus diseases caused by rickettsia Obligate intracellular parasites Spread by arthropod vector and reservoir Infect mostly endothelial cells of vascular system Biology Short, nonmotile, gram negative bacilli Not grown on cell free agar – Grown on yolk sacs of embryonated eggs Endemic typhi Murine typhus Diagnosis Isolation is NOT recommended: highly infectious Immunohistochemical test Immunofluorescent Test PCR Viral Diseases of the Cardiovascular and Lymphatic Systems Dengue Fever Introduction Genus: Flavivirus Has 4 serotypes (DEN-1, 2, 3, 4) Composed of single-stranded positive sense RNA 2 Vectors of dengue virus in the Philippines: Aedes aegypti Aedes albopictus Day-biting, short distance flight Pathogenesis Dengue fever, or Saddleback fever, or Breakbone fever – Dengue Suspect – Probable Dengue – Dengue Fever without Warning Signs – Dengue Fever with Warning Signs – Severe Dengue Fever Saddleback Fever 2 – 7 days fever (viral load) – 2 peaks Subside on the 3rd day Rise again 5 – 8 days after onset Breakbone Fever Myalgia, Deep bone pain When to consider DF? Lives in or travels to dengue-endemic area with fever 2-7 days PLUS any TWO of the following: Headache, Body malaise, Myalgia, Arthralgia, Retro-orbital pain, Anorexia, Nausea, Vomiting, Diarrhea, Flushed skin, Rash (maculopapular, petechial, Hermann’s sign) Dengue Case Classification Suspect Dengue: manifestations only but without laboratory results Probable Dengue: suspect dengue PLUS laboratory test (NS1 antigen test and leukopenia with or without thrombocytopenia) (IgM is optional) Confirmed Dengue: Viral isolation culture, Polymerase Chain Reaction (PCR), Nucleic Acid Amplification Test-Loop Mediated Amplification Assay (NAAT-LAMP), Plaque Reduction Neutralization Test (PRNT) Typical Course of CBC with platelet according to Phase of Dengue Fever What physical examination maneuver will you do to check capillary fragility? Tourniquet Test – Inflating a blood pressure cuff to a point midway between the systolic and diastolic pressures for five minutes. – Positive: 10 or more petechiae per sq. inch DHF: 20 petechiae or more. – FALSE Negative: obese, profound shock Tourniquest test + leukopenia + clinical signs – 70-80% positive predictive value cytokines Antibody Dependent Enhancement Theory Original Antigenic Sin Theory Laboratory Diagnosis Upon arrival at the ER – NS1, IgG, IgM – CBC with platelet Confirmatory: – Viral isolation culture – Polymerase Chain Reaction (PCR), – Nucleic Acid Amplification Test-Loop Mediated Amplification Assay (NAAT-LAMP) – Plaque Reduction Neutralization Test (PRNT) Classify serological response classification of the patient: Result Interpretation NS1 (+); IgM (+/-) IgG (-) Primary infection with one of the strains NS1 (-); IgM (-) IgG (+) Past infection NS1 (+/-); IgM (+) IgG (+) Primary infection with one of the strains but is on recovery stage NS1 (+/-); IgM (+) IgG (+) Past infection with one of strains and acute infection with another strain Management Anti-pyretic: Paracetamol, TSB – Strictly no NSAID, aspirin, steroids Hydration – Oral: ORS, fruit juices (NOT plain water) – Food: No black, brown or red food – IVF: isotonic crystalloids, volume expander if warranted Blood transfusion – FWB or PRBC, FFP – Platelet: only if patient is taking antiplatelet; Platelet conc transfusion may worsen congestion Dengue Vaccine World Health Organization – 9-45 years old; Dose: 0-6-12 months – With prior dengue infection ONLY *People who have not been infected with dengue virus, Dengvaxia appears to act like a first dengue infection – without actually infecting the person with wild-type dengue virus – such that a subsequent infection can result in severe dengue disease. Chikungunya Introduction The name ‘chikungunya’ derives from a root verb in the Kimakonde language, meaning "to become contorted" and describes the stooped appearance of sufferers with joint pain. CHIKV – Central/East Africa in 1950s – virus circulate in a sylvatic cycle between forest-dwelling Aedes species mosquitoes and nonhuman primates – sporadic human cases occur – large human outbreaks are infrequent Biology RNA virus Togavirus Vector: Aedes spp  Key Facts: other symptoms a viral disease that is causes fever and severe include muscle pain, spread by mosquitoes joint pain headache, nausea, fatigue and rash shares some clinical signs with dengue, and there is no cure for the can be misdiagnosed in disease areas where dengue is common.  Key Facts: treatment is focused on relieving the symptoms proximity of mosquito breeding sites to human habitation is a significant risk factor for chikungunya the disease occurs in Africa, Asia and the Indian subcontinent in recent decades mosquito vectors of chikungunya have spread to Europe and the Americas 2007, disease transmission was reported for the first time in Europe, in a localized outbreak in north-eastern Italy.  Transmission virus is transmitted from human to human by the bites of infected female mosquitoes Aedes aegypti & Aedes albopictus biting throughout daylight hours with peaks of activity in the early morning and late afternoon; both species are found biting outdoors, but Ae. aegypti will also readily feed indoors after the bite of an infected mosquito, onset of illness occurs usually between four and eight days but can range from two to 12 days. Manifestations ✓SYMPTOMS: ▪ high fever and severe joint pain that start suddenly ▪ headache ▪ muscle pain ▪ Rash ▪ Not all individuals infected with the virus develop symptoms ▪ Chikungunya (CHIK) does not often result in death, but the symptoms can be disabling, and some people may get severe complications Comparison of the Clinical Features of Chikungunya Fever and Dengue Fever. Complications Common among infants (65 y/o) or immunocompromised Myocarditis, Meningoencephalitis, Mild hemorrhage Guillain-Barre Syndrome, Acute flaccid paralysis, Palsies Uveitis, Retinitis Diagnosis Blood Tests – Leukopenia, Thrombocytopenia – Hypocalcemia – mild to moderate increase in liver function test results ELISA: may confirm the presence of IgM and IgG anti-chikungunya antibodies – IgM peaks at three to five weeks after the onset of illness and persist for about two months Confirmatory: PCR, Viral isolation technique Management No specific medication available to treat CHIK No vaccine to prevent CHIK *Avoiding mosquito bites is the key to avoid chikungunya fever (CHIK) Epstein Barr Virus Biology Herpesviridae Linear dsDNA Icosahedral Enveloped HHV-4 Tropism to B lymphocytes (C3 receptor) Transmission Oral contact→ KISSING DISEASE respiratory secretions minority of cases: blood transfusion & venereal  Epstein Barr Infection of oropharyngeal Virus in Saliva epithelial cells Infection of B Pharyngitis cells B cell Viral shedding in Formation of proliferation saliva heterophile Expression of EBV early proteins Enlagement of liver, spleen, and lymph Atypical nodes T-cell activation Lymphocytes Manifestations 1. Infectious Mononucleosis – Pharyngitis lymphadenopathy, fever, rash – (+) heterophile antibody formation – slow recovery with relapses – Rare complication: Splenic Rupture 2. Nasopharyngeal Carcinoma Burkitt’s Lymphoma Most common childhood cancer in Africa Occur in patients with weak immune systems HP: starry sky pattern Treatment: Supportive Diagnosis Lymphocytosis with atypical lymphocytes (Downy cell) – “mononucleosis” refers to lymphocytes with unusual lobed nuclei that proliferate in the blood during the acute infection Fluorescent-antibody test detects IgM antibodies: most diagnostic method Nucleic acid hybridization –most sensitive Diagnosis Serology (Monospot test) detection of heterophile antibody Epstein-Barr virus specific antibody tests 1. viral capsid antigen (VCA) IgM- recent infection IgA- nasopharyngeal CA 2. Early antigens (EA) Antibody Burkitt Lymphoma & Nasopharyngeal Ca 3. EB Nuclear Antigen (EBNA) Past infection Management Supportive measures: Rest and analgesia Avoidance of excessive physical activity during the first month Severe tonsillar hypertrophy: steroids Cytomegalovirus Biology Herpesviridae Linear dsDNA Icosahedral Enveloped HHV-5 Site of latency: White blood cells and endothelial cells Pathogenesis & Pathology in Normal Hosts Person-to-person transmission (close contact with virus- bearing material) 4-8 week incubation period in normal older children and adults after viral exposure Systemic infection Pathogenesis & Pathology in Normal Hosts 1. Subclinical (MC) 2. Long latent infection 3. Lung, liver, esophagus, colon, kidneys, monocytes, T and B lymphocytes 4. Infectious mononucleosis-like syndrome Manifestations Disease – Asymptomatic infection: MCC manifestation – Congenital disease of newborn: MCC of congenital abnormalities – CMV retinitis: MCC of blindness in HIV patients – Heterophile-negative infectious mononucleosis Pathogenesis in ICH Primary infection is more severe than in normal hosts Greatest Risk Organ transplant recipients Patients on chemotherapy AIDS Viral excretion: increased and prolonged Infection – more apt to dissemination Pneumonia – most common complication Pathogenesis in Congenital Infection MC intrauterine infection associated with developmental defects and mental retardation Congenital CMV infection – Petechiae (BLUEBERRY MUFFIN rash), hepatosplenomegaly, microcephaly, chorioretinitis  Congenital CMV Infection Sources Infections by Breast Milk: immune complexes cytomegalovirus Toddlers: urine, saliva and birth defects in Sex: semen, cervical secretions symptomatic and asymptomatic Uterine Infection children Placental Infection Primary Recurrent Fetal transmission 20-40% 0.2-2.2% Symptomatic (5-10%) Asymptomatic (90-95%) IUGR, microcephaly, Hepatosplenomegaly, retinitis Permanent damage Death Late sequelae (7-25%) (50-80%) (20%) Deafness, learning Mental retardation, deficiencies deafness, blindess Diagnosis Gold Standard – Isolation of the virus from buffy coat of blood, internal fluids, tissues, urine, respiratory secretions Serologic testing – Heterophile negative Characteristic Cytopathic Effect Perinuclear cytoplasmic inclusions Intranuclear inclusions Presence multinucleated cells with Owl’s eye appearance CMV Retinitis Management Ganciclovir – a nucleoside used successfully to treat life threatening cytomegalovirus infections in immunocompromised patients Reduced severity of retinitis, esophagitis and colitis Reduced incidence of pneumonia in bone marrow allograft recipients Controls progressive hearing loss in neonates with congenital infections Foscarnet – analog of inorganic pyrophosphate Recommended for retinitis Acyclovir and Valacyclovir Some benefits in bone marrow/kidney transplant patients Treatment Emerging Viral Hemorrhagic Fevers Filoviridae ▪ Thread-like viruses ▪ Human Pathogens ▪ Marburg virus ▪ Ebola virus Ebola and Marburg Virus Zoonotic: From infected African green monkeys Transmission: Direct contact with infected secretions especially blood Disease: African hemorrhagic fever Detection: ELISA for detection of viral Ag and Ab, cell culture Treatment of Ebola Virus Disease Treatment: Maintaining renal function and electrolyte balance and combating hemorrhage and shock mAB114 (ansuvimab-zykl) REG-EB3 (atoltivimab, maftivimab, and odesivimab-ebgn) Bunyaviridae ▪ Human Pathogens ▪ Mosquito-borne ▪ Sandfly fever virus ▪ Rift Valley fever virus ▪ Hantaan virus (Korean hemorrhagic fever) ▪ Zoonotic Gangrene Gangrene Death of soft tissue resulting from loss of blood supply Predisposing Conditions – Diabetes – Atherosclerosis – Peripheral arterial disease – Trauma or injury – Raynaud's phenomenon (a condition in which the blood vessels that supply the skin become intermittently narrowed) Clostridium perfringens Gram positive Endospore-forming anaerobes Widely found in soil and in GIT of humans and domesticated animals Types Dry gangrene – Poor circulation – Infection is typically not present in dry gangrene → Hands and Feet – Predisposition: Diabetes and Autoimmune diseases – Can lead to wet gangrene if it becomes infected Types Wet gangrene – Almost always involves an infection → spread quickly throughout the body → Very serious and potentially life- threatening condition if not treated quickly. – "wet" because of pus – Burns, or trauma where a body part is crushed or squeezed, can rapidly cut off blood supply to the affected area, causing tissue death and increased risk of infection Types Internal gangrene – inside the body – usually related to an infected organ such as the appendix or colon Fournier's gangrene – infection in the genital area – Men are affected more often than women – infection gets into the bloodstream- sepsis (life-threatening) Types Gas gangrene – rare but dangerous – infection develops deep inside the body (e.g inside muscles or organs, usually as a result of trauma) – clostridia, release dangerous toxins or poisons along with gas which can be trapped within body tissue – warrants immediate medical treatment – Without treatment, death can occur within 48 hours. Management Most common medical treatments – DEBRIDEMENT – AMPUTATION – ANTIBIOTICS: Penicillin, clindamycin Internal gangrene – hyperbaric chamber (pressurized oxygen-rich atmosphere) Oxygen saturates infected tissue Hyperbaric Oxygen Therapy: How This Treatment Works Prevents growth of obligate anaerobe Clostridia PREVENTION – Prompt cleaning of serious wounds and precautionary antibiotic treatment THANK YOU! THANK YOU! THANK YOU!