Emerging Infectious Disease & Potential Agents of Bioterrorism Lecture Notes PDF

PATHOLOGY | TRANS 4D LE Emerging Infectious Disease and Potential 02 Agents of Bioterrorism ARLENE M. SANT...

PATHOLOGY | TRANS 4D LE Emerging Infectious Disease and Potential 02 Agents of Bioterrorism ARLENE M. SANTOS, MD | Lecture Date (09/27/2024) | Version 1 OUTLINE ▪ Previously known agents whose role in specific I. Newly Emerging Infectious II. Potential Agents of diseases has previously gone recognized Diseases and Reemerging Bioterrorism → Examples of NEID: Infectious Diseases A. Definition ▪ SARS-CoV-2 A. Emerging Infectious B. Categories ▪ HIV/AIDS Diseases and Infections C. Biological Warfare before ▪ SARS (NEID) Microbiology Era ▪ MERS B. Reemerging Infectious D. Crucial Biological Agents Diseases (REID) E. Anthrax ▪ H1N1 Influenza C. Successive Stages of 1. Mode of Transmission ▪ Ebola Emergence 2. Pathogenesis ▪ Chikungunya D. COVID-19 3. Epidemiology 1. Etiology 4. Clinical Forms B. REEMERGING INFECTIOUS DISEASES (REID) 2. Mode of Transmission 5. Pathological Findings Caused by the reemergence of infectious agents whose 3. Pathogenesis 6. Diagnostic Tests incidence had significantly declined in the past but whose 4. Microscopic Findings 7. Treatment incidence of disease has reappeared. 5. Common Radiographic 8. Prevention → Examples of REID: Findings 9. Why is Anthrax used ▪ Dengue Virus infection 6. Common Laboratory as a Weapon? Abnormalities 10. How dangerous is ▪ West Nile Virus infection 7. Clinical Findings Anthrax? ▪ Cholera 8. Diagnosis 11. What might an Anthrax ▪ Poliovirus infection 9. Treatment attack look like? C. SUCCESSIVE STAGES OF EMERGENCE 10. Preventive Measures III. Review Questions E. Acute Lung Injury and IV. References Adaptation to a new host Acute Respiratory V. Formative Quiz Epidemic / Pathogenic stage Distress Syndrome Endemic stage (Diffuse Alveolar A fully adapted stage in which the organism may become Damage)Etiology nonpathogenic & potentially even beneficial to the new 1. Acute Lung Injury (ALI) host (e.g., human gut microbiome) 2. Acute Respiratory Distress Syndrome D. COVID-19 (ARDS) ETIOLOGY 3. ALI and ARDS Latin: “Corona” (crown, halo) as in surface projections on 4. Pathogenesis electron microscopy 5. Clinical Course Most known human coronaviruses 6. Stages of DAD Table 1. COVID-19 Profile Must Lecturer Book Previous Youtube Severe Acute Respiratory Distress ❗️ Know 💬 📖 📋 Trans 🔺 Video Infectious Agent Syndrome Coronavirus 2 (SARS-CoV-2) SUMMARY OF ABBREVIATIONS Characteristic Enveloped, single-stranded RNA virus NEID Newly Emerging Infectious Diseases Family Coronaviridae REID Reemerging Infectious Diseases Beta Coronaviruses EID Emerging Infectious Diseases Genus (SARS-CoV-2; SARS; MERS) SARS-CoV Severe Acute Respiratory Syndrome Transmission Zoonotic transmission Coronavirus 2 Natural Reservoir Bats MERS-CoV Middle East Respiratory Syndrome Intermediate host Pangolin Coronavirus SARS-CoV-2 → infect lower I. NEWLY EMERGING INFECTIOUS DISEASES AND Pathogenesis respiratory tract→ severe & fatal REEMERGING INFECTIOUS DISEASES respiratory syndrome in humans A. EMERGING INFECTIOUS DISEASES AND Mild upper respiratory illness in INFECTIONS (EID) Disease immunocompetent individuals (ex. Infections that have recently appeared within a Common cold) population or those whose incidence or geographic range MODE OF TRANSMISSION is rapidly increasing or threatens to increase in the Respiratory droplets near future. → Face to face exposure → May be caused by: → Coughing, sneezing, shouting, etc. ▪ Previously undetected or unknown infectious agents → Most common mode of transmission ▪ Known agents that have spread to new geographic locations or new populations LE 2 TG 3 | J. Pastor, P. Palima, K. Paradero, K. TE | A. Tolentino, S. Ruiz AVPAA | J. Tiosejo PAGE 1 of 10 TRANS 4D Paradero, M. Pascual, VPAA | E. Punzalan PATHOLOGY | LE 1 Emerging Infectious Disease and Potential Agents of Bioterrorism | Arlene M. Santos, MD *This section was directly lifted from the journal reading assignment, Pulmonary edema can fill the alveolar spaces with hyaline Contaminated surfaces membrane formation, compatible with early-phase acute → Viral load appears to persist at higher levels on respiratory distress syndrome. impermeable surfaces (e.g., stainless steel and plastic) Characteristic features of COVID-19: than permeable surfaces (e.g., cardboard). → Endothelial barrier disruptions → Virus has been identified on impermeable surfaces for → Dysfunctional alveolar-capillary oxygen transmission up to 3 to 4 days after inoculation. → Impaired oxygen diffusion capacity Aerosol spread → Estimated 48% to 62% of transmission may occur via MICROSCOPIC FINDINGS presymptomatic carriers Maternal COVID-19 → Low risk for vertical transmission → Mothers' infection with SARSCoV-2 occurred in the third trimester of pregnancy: NO maternal deaths and a favorable clinical course in the neonates. → Presymptomatic transmission is thought to be a major contributor to the spread of SARS-CoV-2. → Centers for Disease Control and Prevention recommend isolating for at least 10 days after symptom onset and 3 days after improvement of symptoms. PATHOGENESIS *This section was directly lifted from the journal reading assignment, 2025 and 2026 transes about Emerging Infectious Diseases & Potential Agents of Bioterrorism. SARS-CoV-2 targets cell through the viral structural spike (S) protein that binds to the angiotensin-converting enzyme 2 (ACE2) receptor Type 2 transmembrane serine protease (TMPRSS2), present in the host cell, promotes viral uptake by cleaving ACE2 and activating the SARS-CoV-2 S-protein. Viral inflammatory response, consisting of both the innate and the adaptive immune response (comprising humoral and cell mediated immunity) impairs lymphopoiesis and increases lymphocyte apoptosis. Upregulation of ACE2 receptors from ACE inhibitor and Figure 1. Microscopic findings in SARS CoV 2 [Lecturer’s PPT] angiotensin receptor blocker medications → increase susceptibility to SARS-CoV-2 infection. A. Tracheitis → However, previous use of ACE Inhibitors and B. Denudation of tracheal epithelium Angiotensin Receptor Blockers (ARBS) in individuals → Submucosal epithelium, submucosal congestion, infected with COVID-19 was NOT associated with risk mononuclear inflammation of infection or hospital mortality. C. Diffuse alveolar damage: Exudative phase ACE2 & TMPRSS2: Expressed in alveolar epithelial type → Hyaline membranes (black arrow) lining alveolar II of the host target cells. spaces: pathologic manifestation of acute Similar to other respiratory viral diseases (influenza), there respiratory distress syndrome may be profound lymphopenia in individuals with D. Diffuse alveolar damage: Proliferative phase COVID-19 when the virus infects and kills T-lymphocyte → Proliferation of type II pneumocytes (black arrow): Type II pneumocytes proliferate to replace injured type I EARLY STAGE pneumocyte Viral copy numbers can be high in the lower respiratory E. Diffuse alveolar damage: Proliferative phase tract. → Atypical pneumocytes: Reaction to the inflammation Inflammatory signaling molecules are released by F. Bronchopneumonia infected cells and alveolar macrophages in addition to → Filling of alveolar spaces by neutrophils & patchy recruited T lymphocytes, monocytes, & neutrophils. hemorrhage: characteristic finding in LATE STAGE bronchopneumonia Viral infection accelerates compromising COMMON RADIOGRAPHIC FINDINGS epithelial-endothelial barrier integrity. Chest radiographic imaging Infections of the pulmonary capillary endothelial cells → → Bilateral lower lobe predominant infiltrates Accentuates inflammatory response → Influx of Chest computed tomography imaging monocytes and neutrophils → Bilateral, peripheral lower lobe ground-glass Diffuse thickening of the alveolar wall with mononuclear opacities cells and macrophages infiltrating airspaces in addition to endothelialitis. Interstitial mononuclear inflammatory infiltrates and edema may develop → Appear as ground-glass opacities on computed tomographic imaging PATHOLOGY Emerging Infectious Disease and Potential Agents of Bioterrorism PAGE 2 of 10 PATHOLOGY | LE 1 Emerging Infectious Disease and Potential Agents of Bioterrorism | Arlene M. Santos, MD COMMON LABORATORY ABNORMALITIES Serological tests: Lymphopenia → Includes point-of-care assays and high throughput → Abnormally low levels of lymphocytes enzyme immunoassays. → Kills T-lymphocytes → Aid in the diagnosis and measurement of responses Elevated inflammatory markers to novel vaccines → ESR (erythrocyte sedimentation rate) → However, presence of antibodies may NOT confer → CRP (C-reactive protein) immunity because NOT all antibodies produced in → Ferritin response to infection are neutralizing → TNF (tumor necrosis factor) IgM: detectable within 5 days of infection → Interleukin-6 (IL-6) → Higher during weeks 2-3 of illness Abnormal coagulation parameters IgG: approximately 14 days after symptom onset → Prolonged PTT (prothrombin time) Higher antibody titers occur with more severe disease → Thrombocytopenia TREATMENT → Elevated D-dimer Pharmacologic measures → Low levels of fibrinogen → Dexamethasone (in recent trials) Severe cases ▪ Decreases mortality → There is activation of coagulation and consumption of ▪ Limited to patients who require supplemental clotting factors oxygen and who have symptoms for >7 days → Inflamed lung tissues and pulmonary endothelial cells → Remdesivir may result in microthrombi formation. ▪ Improves time to recovery → A report from Wuhan, China, indicated that 71% of 183 ▪ Limited to patients NOT receiving mechanical individuals who died of COVID-19 met criteria for ventilation diffuse intravascular coagulation (DIC). Supportive care CLINICAL FINDINGS → Supplemental oxygen; Ventilation Incubation period: Approx. 5 days → Main treatment for most patients Symptom development: 11.5 days PREVENTIVE MEASURES Most common symptoms: Use of face masks → Fever Physical distancing → Dry cough Vaccination → Shortness of Breath (SOB) Hand disinfection Other Symptoms: Environmental disinfection → Weakness, Fatigue → Nausea and vomiting E. ACUTE LUNG INJURY & ACUTE RESPIRATORY → Diarrhea DISTRESS SYNDROME (DIFFUSE ALVEOLAR 📖 → Anosmia: Loss or impairment of sense of smell DAMAGE) → Aguesia: Loss or impairment of sense of taste Not fully discussed in the PPT. Contents came from Robbins & Cotran Pathologic Basis of Disease 10th edition. Common complications, among hospitalized patients: → Pneumonia ACUTE LUNG INJURY (ALI) → Acute Respiratory Distress Syndrome (ARDS) Characterized by the abrupt onset of hypoxemia and → Acute Liver injury bilateral pulmonary edema in the absence of cardiac → Cardiac injury failure (non-cardiogenic pulmonary edema) → Prothrombotic coagulopathy ALI is a well-recognized complication of diverse → Acute kidney injury conditions including both pulmonary and systemic → Neurologic manifestations disorders → Shock In other uncommon instances, ALI appears acutely in the Collectively, characteristic features of COVID-19 are: absence of known triggers and follows a rapidly → Endothelial barrier disruption progressive clinical course, a condition known as acute → Dysfunctional alveolar capillary oxygen transmission interstitial pneumonia. → Impaired oxygen diffusion capacity ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) DIAGNOSIS Manifestation of severe ALI *This section was directly lifted from the journal reading assignment, Progressive respiratory insufficiency caused by diffuse 2025 and 2026 transes about Emerging Infectious Diseases & alveolar damage in the setting of sepsis trauma or Potential Agents of Bioterrorism. pulmonary infection Reverse transcription Polymerase Chain Reaction ALI AND ARDS (RT-PCR) Both are associated with: → SARS-CoV-2 RNA detection from respiratory samples → Inflammation-associated increase in pulmonary vascular (nasopharynx) via nasal swab is the standard of permeability diagnosis. → Edema Due to false-negative result rates of SARS-CoV-2 PCR: → Epithelial cell death Clinical, laboratory, and imaging findings may also be → Histological manifestations: Diffuse alveolar damage used to make a presumptive diagnosis (DAD) → Factors contributing to false-negative results: ▪ Adequacy of the specimen collection technique ▪ Time from exposure ▪ Specimen source PATHOLOGY Emerging Infectious Disease and Potential Agents of Bioterrorism PAGE 3 of 10 PATHOLOGY | LE 1 Emerging Infectious Disease and Potential Agents of Bioterrorism | Arlene M. Santos, MD PATHOGENESIS OF ARDS/ALI Epidemiologic studies show that ALI or ARDS is more Initiated by injury of pneumocytes and pulmonary common and has a worse prognosis in chronic endothelium, vicious cycle of increasing inflammation and alcoholics and smokers pulmonary damage There are no proven specific treatments for ARDS Endothelial Activation → Most survivors recover pulmonary function, but in a → Important early event minority of patients, the lung damage results in → In some instances, it is secondary to pneumocyte injury, interstitial fibrosis and chronic pulmonary disease which is sensed by resident alveolar macrophages → Secretion of TNF acts on neighboring endothelium STAGES OF DIFFUSE ALVEOLAR DAMAGE (DAD) → Inflammatory cells may activate pulmonary ACUTE PHASE endothelium directly during sepsis or severe tissue MACROSCOPIC FINDINGS injury (Respiratory System) Adhesions and extravasation of neutrophils → Neutrophils adhere to activated endothelium and migrate into the interstitium and the alveoli ▪ Where degeneration & release of inflammatory mediators; proteases, reactive oxygen species (ROS), and cytokines occurs. → Experimental evidence suggests that neutrophil extracellular traps (NETs) are also released thus contributing to direct lung damage Accumulation of intra-alveolar fluid & formation of hyaline membranes → Endothelial activation & damage → Leaky pulmonary capillaries → Intra-alveolar edema due to interstitial and intravascular fluid ▪ Damage and necrosis of type II alveolar pneumocytes lead to surfactant abnormalities, further compromising alveolar gas exchange. ▪ Protein-rich edema fluid and debris from dead alveolar epithelial cells organize into hyaline Figure 2. Gross Lung - Acute Phase of DAD [Lecturer’s PPT] membranes which is a characteristic features of ALI/ARDS Lungs: Resolution of injury Red, heavy due to edema → Impeded in ALI/ARDS due to epithelial necrosis & Firm and Boggy inflammatory damage that impairs the ability of Consolidated and hypo crepitant remaining cells to assist with edema resorption MICROSCOPIC FINDINGS → If inflammatory stimuli decrease, macrophages can now remove intra-alveolar debris and release fibrogenic cytokines; TGF-B and PDGF → Transforming growth factor β (TGF-β) and platelet-derived growth factor (PDGF) stimulate fibroblast growth and collagen deposition, leading to fibrosis of alveolar walls. → Residual type II pneumocytes proliferate to replace Type I pneumocytes, reconstructing the alveolar lining CLINICAL COURSE OF ALI/ARDS Clinical Features → Profound dyspnea and tachypnea usually start ALI/ARDS, followed by increasing respiratory failure, hypoxemia, cyanosis, and the appearance of diffuse bilateral infiltrates on radiographic examination. Figure 3. Hyaline Membrane Formation - Acute Phase of → Hypoxemia DAD [Robbins & Cotran Pathologic Basis of Disease 8e] ▪ May be refractory to oxygen therapy due to Congestion ventilation-perfusion mismatch, and respiratory Intra-alveolar edema acidosis Interstitial edema → Early lung stiffness Inflammation ▪ Due to loss of functional surfactants, leading to ❗️ Fibrin deposition intubation & high ventilatory pressures maintain Hyaline membrane formation (black arrow) adequate gas exchange Alveolar collapse in some areas → Refer to table 5. about the conditions associated with Alveolar distension in other areas development of ARDS Desquamation of alveolar epithelial cells Superimposed bronchopneumonia (fatal cases) PATHOLOGY Emerging Infectious Disease and Potential Agents of Bioterrorism PAGE 4 of 10 PATHOLOGY | LE 1 Emerging Infectious Disease and Potential Agents of Bioterrorism | Arlene M. Santos, MD PROLIFERATIVE/ORGANIZING PHASE CATEGORY C PRIORITY PATHOGENS MICROSCOPIC FINDINGS 3rd highest priority organisms/biological agents Include emerging pathogens that could be engineered for mass dissemination in the future because of: → Availability → Ease of production & dissemination → Potential for high morbidity and mortality rates & major public health impact Table 2. Examples of Pathogens for each category Category Pathogen Disease Bacillus anthracis Anthrax Clostridium botulinum Botulism Yersinia Pestis Plague A Variola major Smallpox Francisella tularensis Tularemia Viruses causing viral Dengue hemorrhagic fever Ebola Figure 4. [Left] Arrows - Hyaline membranes; Asterisks - Fibroblastic proliferation; Arrowhead - Reactive Pneumocytes Bacteria: [Lecturer’s PPT] Diarrheagenic [Right] - Fibrin blood clots w/in small to medium-sized Escherichia coli pulmonary arteries [Lecturer’s PPT]] Pathogenic Vibrio cholera Shigella spp. Granulation tissue formation; Results to fibrosis or Salmonella spp. resolution Campylobacter jejuni Type II pneumocyte hyperplasia Food-borne and water-borne Virus: CHRONIC PHASE infections Hepatitis A virus Macroscopic Lungs heavy due to fibrosis Findings Protozoa: B Entamoeba histolytica II. POTENTIAL AGENTS OF BIOTERRORISM A. DEFINITION Fungi: BIOTERRORISM Microsoporida → a biological attack via the intentional release of Coxiella burnetti Q fever viruses, bacteria or other organisms that can sicken or Chlamydia pssitaci Psittacosis kill people, livestock or crops Food-borne → It is the intentional release of a pathogen or a biotoxin Staphylococcus aureus disease; potential against humans, plants & animals. (Enterotoxin B) use as an inhaled → An attack against people which can be used to cause bioweapon illness, cause death, fear, societal disruption and Ricketssia prowazekii Typhus fever economic damage Mosquito-borne Mosquito-borne B. CATEGORIES Encephalitis viruses encephalitis Associated with CATEGORY A PRIORITY PATHOGENS Nipah virus encephalitis Organisms that pose the highest risk to national security Chikungunya virus Chikungunya & public health because they: → Can be easily disseminated or transmitted from Severe Acute person to person SARS-CoV; MERS-CoV Respiratory → Result in high mortality rates & have the potential for Distress Syndrome major public health impact Tick-borne hemorrhagic Tick-borne → Might cause public panic and social disruption C fever viruses hemorrhagic fever → Require special action for public health preparedness Tick-borne encephalitis Tick-borne complex Flaviviruses encephalitis CATEGORY B PRIORITY PATHOGENS Mycobacterium 2nd highest priority organisms/biological agents Tuberculosis tuberculosis → Moderately easy to disseminate Influenza virus Influenza → Result in moderate morbidity rates and low mortality Creutzfeldt-Jakob rates Prions disease (vCJD) → Require specific enhancements for diagnostic capacity and enhanced disease surveillance PATHOLOGY Emerging Infectious Disease and Potential Agents of Bioterrorism PAGE 5 of 10 PATHOLOGY | LE 1 Emerging Infectious Disease and Potential Agents of Bioterrorism | Arlene M. Santos, MD C. EXAMPLES OF BIOLOGICAL WARFARE BEFORE E. ANTHRAX THE MICROBIOLOGY ERA Causative agent: Bacillus anthracis Table 3. Biological Warfare before the Microbiology Era → Gram-positive Year Event → Rod-shaped The Hittites send rams infected with Produce spores that are dormant & can live in the tularaemia to their enemies environment → Spores can live in the soil for decades TULARAEMIA: → When spores enter the body of an animal or humans (a caused by Francisella tularensis place rich in water, sugar & other nutrients), the spores transmitted to humans by an can be activated and turn into active growing cells arthropod vector usually a tick → When they become active, the bacteria can multiply, 14th Century BC spread out in the body, produce toxins and cause or biting fly and also by cutaneous exposure to infected severe illness & death animals MODES OF TRANSMISSION causes necrotizing HOW ANIMALS GET INFECTED pneumonia and necrosis, Through inhalation abscess and granuloma in Through ingestion of spores in contaminated soil, plants lymph nodes or water Mongols hurl bodies of plague victims Domestic and wild animals can get infected (cattle, sheep, 1346 over the walls of the besieged city of goat, antelope and deer) Caffa (Crimea) In areas where domestic animals have been infected by Russian army catapult plague cadavers Bacillus anthracis, routine vaccination can help prevent 1710 over the Swedish troops in Reval outbreaks (Estonia) British officers distribute blankets from HOW HUMANS GET INFECTED 1763 Through breaks in the skin or mucosa smallpox hospital to Native Americans Confederates sell clothing from yellow → Spores enter the body in a cut or scrape in the skin 1863 fever and smallpox patients to Union Through inhalation troops during the American Civil War Through ingestion of food or drinking of water contaminated with Bacillus anthracis spores D. CRUCIAL BIOLOGIC AGENTS AND LIKELY USE AS PATHOGENESIS BIOLOGICAL WEAPONS Includes agents were applied and probably resulted in Entry of spores into the body casualties and were used in war, research or as terror ↓ agents Activated from dormant state Table 4. Crucial Biologic Agents ↓ Disease Multiplication and Proliferation Pathogen Used ↓ Category WW I Dissemination to different parts of the body WW II ↓ Bacillus anthracis Soviet Union Toxin production responsible for the symptoms of anthrax A (Anthrax) 1979 ↓ Japan 1995 Cutaneous, Respiratory or Gastrointestinal Anthrax USA 2001 ↓ Marburg Virus Soviet Bioweapons Death A (Hemorrhagic Fever) Program Vibrio cholera EPIDEMIOLOGY B WW II (Cholera) More common in developing countries without veterinary public health programs that routinely vaccinate animals Solon (600 BC) against anthrax → Athenian general Most common in the agricultural regions of Central and → He contaminated the water supply of the besieged South America, Sub-saharan Africa, Central and Greek city of Cirrha with hellebore root Southwestern Asia, Southern & Eastern Europe and → The inhabitants were crippled with diarrhea which led the Caribbean to their defeat In the US, anthrax is rare but sporadic outbreaks occur in wild and domestic grazing animals (e.g., deer & cattle) Yearly vaccination is recommended CLINICAL FORMS OF ANTHRAX Space intentionally left blank Cutaneous anthrax Inhalational anthrax Gastrointestinal anthrax PATHOLOGY Emerging Infectious Disease and Potential Agents of Bioterrorism PAGE 6 of 10 PATHOLOGY | LE 1 Emerging Infectious Disease and Potential Agents of Bioterrorism | Arlene M. Santos, MD Histologic Findings: → Massive subepidermal edema → Dermal Necrosis → Exudative inflammation with infiltration by neutrophils and macrophages → Numerous thrombosed blood vessels Figure 5. Gram Stain showing large gram-positive bacilli forming spores[Lecturer’s PPT] PATHOLOGIC FINDINGS IN ANTHRAX CUTANEOUS ANTHRAX Most common form → 95% of cases of anthrax are cutaneous Figure 8. Pathologic Findings in Cutaneous Anthrax showing → Starts as painless pruritic papule that develops into a massive subepidermal edema[Lecturer’s PPT] vesicle (within 2 days) then ruptures to form an ulcer ▪ Ulcer becomes covered by a characteristic black eschar which is a dry, dark scab or falling away of dead skin Bacteremia is rare in cutaneous anthrax Figure 9. Pathologic Findings in Cutaneous Anthrax under HPO showing extensive dermal necrosis with a neutrophilic infiltrate[Lecturer’s PPT] Figure 6. Pathologic Findings in Cutaneous Anthrax showing how a papule develops into a vesicle then ruptures to form an ulcer. The ulcer becomes covered by a characteristic black eschar[Lecturer’s PPT] Figure 10. Pathologic Findings in Cutaneous Anthrax showing numerous thrombosed blood vessels[Lecturer’s PPT] Figure 7. Pathologic Findings in Cutaneous Anthrax showing Space intentionally left blank ulcer and black eschar. Eschar refers to the dry, dark scab or falling away of dead skin[Lecturer’s PPT] PATHOLOGY Emerging Infectious Disease and Potential Agents of Bioterrorism PAGE 7 of 10 PATHOLOGY | LE 1 Emerging Infectious Disease and Potential Agents of Bioterrorism | Arlene M. Santos, MD INHALATIONAL ANTHRAX DIAGNOSTIC TESTS GROSS FINDINGS Blood Lungs - Pleural effusion; Pulmonary edema; Foci of → Gram Stain hemorrhage ▪ Gram positive rods; spores maybe apparent Perihilar & Peribronchial Lymph nodes - enlarged & → Capsule Stain hemorrhagic ▪ India ink inclusion Respiratory symptoms ▪ McFadyean reaction (polychrome methylene blue) → High fever, shortness of breath, tachypnea, diaphoresis, ▪ Direct Fluorescent antibody stain w/ antibodies chest pain specific for polyglutamate capsule Inhalational Anthrax HISTOLOGIC FINDINGS → Chest x-ray or CT scan to confirm mediastinal widening Lungs or pleural effusion → Perihilar interstitial pneumonia For confirmation of anthrax: ▪ Macrophages & neutrophils → Testing for Bacillus anthracis in samples (blood, skin → Pulmonary vasculitis lesion swab, spinal fluid, or respiratory secretions) → Hyaline membrane formation ❗️ → Measure antibodies or toxins in the blood Mediastinal Lymph Nodes Culture → Necrosis → Gold standard for diagnosis → Lymphocytosis → Immunohistochemistry with antibodies against cell wall → Macrophages w/ phagocytosed apoptotic lymphocytes & capsule is extremely helpful → Fibrin-rich edema fluid Other ancillary tests: → Immunofluorescence → Polymerase chain reaction → Serologic testing using ELISA TREATMENT ❗️ Antibiotics → DOC: Ciprofloxacin → Cutaneous anthrax: Antibiotic therapy does not change the natural progression of disease, but prevents dissemination PREVENTION Vaccination Decontamination Prophylactic Treatment Figure 11. Pathologic Findings in Inhalational Anthrax of the mediastinal lymph nodes showing colonies of Bacillus WHY WOULD ANTHRAX BE USED AS A WEAPON? anthracis in the capillaries (Giemsa stain). Characteristic Anthrax spores → Easily found in nature; can be produced in the lab and ❗️ histologic finding is the presence of Bacillus anthracis in the capillaries at the site of infection [Lecturer’s PPT] can last for a long time in the environment → A good weapon because it can be released quietly and without anyone knowing ▪ Have been used as a weapon before → Microscopic Anthrax spores can be put into powders, sprays, food and water. ▪ Because they are so small, you may not be able to see, smell or taste them. ▪ In 2001, powdered anthrax spores were mailed through the US Postal System; 22 people including 12 mail handlers got anthrax and 5 of these 22 died HOW DANGEROUS IS ANTHRAX? Classified as category or tier 1 because it poses the greatest risk for deliberate misuse. Significant potential for mass casualties; devastating effect Figure 12. Pathologic Findings in Inhalational Anthrax seen to the economy, critical infrastructure or public confidence. A severe threat to public health and safety. ❗️ in the mediastinal lymph node with characteristic necrosis [Lecturer’s PPT] WHAT MIGHT AN ANTHRAX ATTACK LOOK LIKE? Placed in letters and mailed GASTROINTESTINAL ANTHRAX Put in food or water Usually contracted by eating undercooked meat Released into the air from a truck, building or plane contaminated with Bacillus anthracis If not detected by the monitoring systems in the US, Initially, the person has nausea, abdominal pain, and doctors will see unusual patterns of illness among sick vomiting, followed by severe bloody diarrhea & sometimes, people showing up at the emergency rooms. bacteremia Mortality: approximately 40% PATHOLOGY Emerging Infectious Disease and Potential Agents of Bioterrorism PAGE 8 of 10 PATHOLOGY | LE 1 Emerging Infectious Disease and Potential Agents of Bioterrorism | Arlene M. Santos, MD III. REVIEW QUESTIONS 1. Which of the following is an example of a newly ANS: emerging infectious disease (NEID)? 1. C. SARS-CoV 2, HIV/AIDS, H1N1 Influenza are examples a. SARS-CoV-2 of newly emerging infectious diseases (NEID). Cholera is a b. HIV/AIDS reemerging infectious disease (REID.) c. Cholera 2. B. Lymphopenia (abnormally low levels of lymphocytes) is d. H1N1 Influenza a finding in patients infected with COVID. 2. The following are the common laboratory 3. C. Endothelial activation is an important early event. In abnormalities during COVID-19 infection, EXCEPT: some instances, endothelial activation is secondary to a. Elevated CSR pneumocyte injury, which is sensed by resident alveolar b. Elevated lymphocytes macrophages. In response, these immune sentinels c. Elevated ERP secrete mediators such as tumor necrosis factor (TNF) that d. Elevated ferritin act on the neighboring endothelium. 3. What event in the pathogenesis of ALI/ARDS is 4. B. Coxiella burnetti belongs to Category B, which is the considered an important early event, and in some 2nd highest priority. It is the causative agent of Q fever. instances, secondary to pneumocyte injury? a. Adhesion and extravasation of neutrophils IV. REFERENCES b. Accumulation of intra-alveolar fluid and formation of Batch 2025. Emerging Infectious Disease and Potential Agents of hyaline membranes Bioterrorism [Transcription]. c. Endothelial activation Batch 2026. Emerging Infectious Disease and Potential Agents of Bioterrorism [Transcription]. d. Resolution of injury Kumar, V., Abbas, A. K., Aster, J. C., & Robbins, S. L. (2020). Robbins & 4. Which category of bioterrorism agents does Coxiella Cotran Pathologic Basis of Disease 10th Edition. Elsevier burnetti belong to? Wiersinga, W. J., Rhodes, A., Cheng, A. C., Peacock, S. J., & Prescott, H. C. (2020). Pathophysiology, Transmission, Diagnosis, and Treatment of a. Category A Coronavirus Disease 2019 (COVID-19). JAMA, 324(8), 782. b. Category B https://doi.org/10.1001/jama.2020.12839 c. Category C d. Category D V. APPENDIX Table 5. Conditions Associated With Development of Acute Respiratory Distress Syndrome [Robbins & Cotran Pathologic Basis of Disease 10th edition] PATHOLOGY Emerging Infectious Disease and Potential Agents of Bioterrorism PAGE 9 of 10 PATHOLOGY | LE 1 Emerging Infectious Disease and Potential Agents of Bioterrorism | Arlene M. Santos, MD Figure 13. Immunopathogenesis of Coronavirus Disease 2019 (COVID-19)[Journal of the American Medical Association] PATHOLOGY Emerging Infectious Disease and Potential Agents of Bioterrorism PAGE 10 of 10