Chapter 20 Infections of the Respiratory Tract PDF

CHAPTER 20 Infections of the Respiratory Tract Copyright © 2021 W. W. Norton & Company, Inc. https://pharmaceutical-journal.com/article/news/monoclonal-antibody-75-effective-against-lower-respiratory-tract-infection-in-infants https://www.washingtonpost.com/nation/2022/03/04/study-finds-lav...

CHAPTER 20 Infections of the Respiratory Tract Copyright © 2021 W. W. Norton & Company, Inc. https://pharmaceutical-journal.com/article/news/monoclonal-antibody-75-effective-against-lower-respiratory-tract-infection-in-infants https://www.washingtonpost.com/nation/2022/03/04/study-finds-lavender-spray-walmart-killed-sickened-patients/ Infections of the Respiratory Tract Chapter Objectives ▪ Relate anatomy and physiology of the respiratory tract to the infectious processes affecting them. ▪ Describe symptoms that can help differentiate upper and lower respiratory infections caused by different microorganisms. ▪ Explain the mechanisms of pathogenesis for major agents of respiratory tract infections. ▪ Relate pathogenic mechanisms to disease prevention strategies for microbes that infect the respiratory tract. 4 The Ominous Cough – 1 Scenario ▪ It was the summer of 1918, and 20-year-old Floyd, a U.S. army private stationed in Kansas, began to feel ill. He visited the camp doctor complaining of a cough, a headache, and some chills. Within a day, Floyd’s fever reached 40°C (104°F). He became incoherent and lost consciousness. When Floyd awoke, he found himself in a large barracks lying on a cot among a long line of cots filled with sick soldiers. 5 The Ominous Cough – 2 Signs and Symptoms ▪ His cough was severe. Floyd saw dark, purplish brown spots appear on the face of the GI lying on the cot next to his. The soldier began to cough blood and eventually his face turned blue from lack of oxygen—a sign that death was imminent. Doctors could do little to help. 6 The Ominous Cough – 3 Resolution ▪ Fortunately, after about 2 weeks, Floyd started to improve. Many others were not so lucky and died. No one knew what caused the disease raging through the camp or how to stop it. 7 20.1 Anatomy of the Respiratory Tract – 1 Section Objectives ▪ List the anatomical differences between the upper and lower respiratory tracts. ▪ Describe the relationship of eyes, ears, and nose with the upper airways. ▪ Explain the role of the mucociliary escalator in respiratory infection processes. 8 20.1 Anatomy of the Respiratory Tract – 2 ▪ Respiratory infections Classified by whether they affect the upper or lower respiratory tract Upper respiratory tract includes – Upper airways (nasal passages) – Oral cavity – Pharynx – Larynx 9 20.1 Anatomy of the Respiratory Tract – 3 ▪ Lower respiratory tract Alveoli are small sacs where oxygen from inhaled air is exchanged for carbon dioxide. All the respiratory tubes warm, moisturize, and remove impurities from inhaled air as it travels to the alveoli. 10 20.1 Anatomy of the Respiratory Tract – 4 ▪ The mucociliary escalator works to keep the lungs devoid of microorganisms. Goblet cells secrete mucin that combines with water to create sticky mucus. Cilia on epithelial cells remove foreign particles, including microorganisms, trapped in the sticky mucus. 11 20.2 Viral Infections of the Respiratory Tract – 1 Section Objectives ▪ Compare and contrast the signs and symptoms of upper and lower respiratory tract infections. ▪ Describe the role of mutations in the genesis of influenza pandemics. ▪ List the risk factors for upper and lower respiratory tract infections. ▪ Identify the etiology of the major viral respiratory infections on the basis of their clinical presentation. 12 Case History: Jacob’s Runny Nose – 1 ▪ Jacob, a rambunctious 5-year-old boy brought to the clinic by his mother, was complaining of a scratchy sore throat, a nonproductive cough (a cough that does not produce sputum), rhinorrhea (a runny nose), nasal congestion (a stopped-up nose), and a headache that started the night before. He did not have a fever. 13 Case History: Jacob’s Runny Nose – 2 ▪ His complete blood count (CBC)—the number of platelets and red and white blood cells in blood, along with its differential (the different types of red and white blood cells)—was normal, as was his chest X-ray. Jacob was diagnosed with the common cold and advised to rest, drink plenty of clear liquids, and use over-the-counter cough suppressants and either ibuprofen or acetaminophen for pain. 14 20.2 Viral Infections of the Respiratory Tract – 2 ▪ Common cold The most frequent viral infection of the upper respiratory tract 200 viral subtypes Rhinoviruses – The most common cause of colds Other prominent players include – Coronaviruses – Influenza – Parainfluenza – Respiratory syncytial virus 15 20.2 Viral Infections of the Respiratory Tract – 3 ▪ Viral sinusitis Infection of the upper airways Inflammation and congestion of the sinuses – Impacted narrow sinus passages can then impede the flow of mucus. Sinus congestion causes the headache that we feel when our nose is “stopped-up” from a bad cold. Resolves on its own 16 Lower Respiratory Tract Viral Infections – 1 ▪ Respiratory syncytial virus (RSV) disease Fusion of adjacent infected cells into a syncytium, a giant cell containing many nuclei ▪ Transmitted from person to person ▪ Young, around age 2 Most common cause of bronchiolitis and pneumonia among infants and children younger than 1 year ▪ Infections occur when the virus comes into contact with mucous membranes of the eyes with mouth or nose through the inhalation of droplets from a sneeze or cough 17 Lower Respiratory Tract Viral Infections – 2 ▪ Influenza Based on antigenic determinants Type A – Cause of epidemics and occasional pandemics – Can infect a variety of animals as well as people – Is constantly changing Type B – Found primarily in humans and usually results in a milder illness – Does not cause pandemics Type C – Causes only mild disease – Does not case epidemics or pandemics 18 Lower Respiratory Tract Viral Infections – 3 ▪ Pathogenicity is dependent on three proteins: Hemagglutinin (HA) – Transmembrane protein that forms the spikes on the viral surface – Binds to N-acetylneuraminic (sialic) acid on the surface of respiratory cells to gain entry Neuraminidase (NA) – On surface releases budding virus from host cell M2 – Releases viral genome into host cell cytoplasm 19 Lower Respiratory Tract Viral Infections – 4 ▪ Why do some strains cause more severe disease than others? Influenza can infect humans, pigs, and birds. – Different viruses can sometimes infect the same cell. Antigenic shift – Eight RNA segments of each flu genome will uncoat. – Mix in the cytoplasm – Re-sort to form a new influenza virus containing a new form of the hemagglutinin gene Antigenic drift – Smaller mutations in the HA and NA genes 20 Lower Respiratory Tract Viral Infections – 5 ▪ Covid-19 SARS-CoV-2 Single-stranded, positive-sense, enveloped RNA virus Emerged December 2019 Symptoms – Flu-like – Cough, fever, shortness of breath – Severe cases include a cytokine storm – Many cases are asymptomatic 21 Lower Respiratory Tract Viral Infections – 6 ▪ Croup Also known as laryngotracheobronchitis (LTB) Infects the larynx Spreads to the trachea and even bronchi Children 6 months to 5 years of age are at the highest risk for contracting the disease. Symptoms include – Fever – Runny nose – “Barking” cough (caused by the swelling of the larynx) Parainfluenza viruses types 1 and 2 are the most common cause of croup. Treatment depends on severity of symptoms. 22 20.3 Bacterial Infections of the Respiratory Tract Section Objectives ▪ List the bacterial etiologies of respiratory tract diseases and each disease’s anatomical location. ▪ Describe the relationships between host and bacteria that contribute to the pathogenesis of respiratory tract infections. ▪ Compare and contrast clinical presentations of bacterial infections of the respiratory tract. ▪ Develop a prevention plan for different bacterial respiratory pathogens. 23 Case History: A Big Pain in a Little Ear ▪ Chloe is a 2-year-old generally healthy child who was brought to the clinic by her father. The child had a fever since the previous night, was irritable, and kept pulling on her left ear. Chloe also had a runny nose for the past 2 weeks. Her temperature was 38.5°C (101.3°F) at the clinic and the physical exam showed a red and swollen ear, an erythematous (reddened) ear canal, and a bulging tympanic membrane. Chloe was diagnosed with acute otitis media and prescribed an antibiotic that she had to take for 7 days. 24 Upper Respiratory Tract Bacterial Infections – 1 ▪ Otitis media Acute otitis media (AOM) Most common diagnosis during a sick child visit to the pediatrician’s office Signs and symptoms are wide ranging and the infections can be caused by – Viruses – Gram-positive and Gram-negative bacteria 25 Upper Respiratory Tract Bacterial Infections – 2 ▪ In infants and young toddlers, the Eustachian tube is shorter and almost horizontal, which makes drainage less optimal. ▪ Bacteria more likely to get trapped in the middle ear and cause an infection. ▪ As we get older, the Eustachian tube lengthens and its path becomes angled, making drainage of the middle ear much easier and ear infections much less likely. 26 Upper Respiratory Tract Bacterial Infections – 3 ▪ Otitis media Three bacterial species are the most frequent cause of AOM in otherwise healthy children: – Streptococcus pneumoniae – Haemophilus influenzae – Moraxella catarrhalis A multivalent polysaccharide vaccine protects against S. pneumoniae 27 Upper Respiratory Tract Bacterial Infections – 4 ▪ Bacterial sinusitis Often accompanies middle ear infection in children and pneumonia in adults Inflammation and congestion obstructs the sinuses and mucus flow. Symptoms include – Pressure behind the eyes – Pain in the face – Foul-smelling nasal discharge or breath Antibiotics is the usual course of treatment. 28 Case History: The Contagious Football Player with GAS – 1 ▪ Dallin, a 16-year-old high school athlete, came to the clinic complaining of a sore throat. He did not have a cough or any cold or flu symptoms. His cervical nodes (lymph nodes in the neck) were enlarged and tender to palpation, there was an exudate visible on his tonsils and pharynx (pharyngotonsilar region), and his temperature was 39.8°C (103.6°F). The physician assistant (PA) told Dallin that he probably had a strep throat but she could not perform a rapid strep test to confirm because they had run out of the strips. 29 Case History: The Contagious Football Player with GAS – 2 ▪ The PA then swabbed the back of Dallin’s throat and sent the sample to the lab for culture and antibiotic sensitivity testing. Dallin was given an antibiotic empirically (based on clinical experience and in the absence of definitive diagnosis). He was told that he was contagious and should rest and avoid contact with others until better. He followed the recommendations, recovered, and was back playing football in a few days. The lab isolated Streptococcus pyogenes, also called group A streptococcus (GAS), from Dallin’s pharyngeal swab, confirming the diagnosis. 30 Upper Respiratory Tract Bacterial Infections – 5 ▪ Pharyngitis: inflammation of the pharynx ▪ Tonsillitis: inflammation of the tonsils ▪ Laryngitis: inflammation of the larynx ▪ Peritonsillar abscess: abscess in the pharynx ▪ Differential diagnosis for a person complaining of a sore throat includes a variety of viral and bacterial etiologies, including infectious mononucleosis and diphtheria. 31 Upper Respiratory Tract Bacterial Infections – 6 ▪ Streptococcal pharyngitis Also known as strep throat Contagious and spread through – Person-to-person contact – Indirect contact with items contaminated by secretions Symptoms include – Sudden onset of high fever and sore throat – Tender, enlarged cervical lymph nodes – Exudate on tonsils – Absence of a cough Treatment with antibiotics 32 Upper Respiratory Tract Bacterial Infections – 7 ▪ Streptococcal pharyngitis Some strains of S. pyogenes produce exotoxins. – Streptococcal pyogenic exotoxins (SPEs) – Can cause fever and a red rash called scarlet fever Rash starts on the head and neck, then spreads to the trunk, then to arms and legs. Some patients may also have a very distinctive red, bumpy tongue referred to as a strawberry tongue. 33 Upper Respiratory Tract Bacterial Infections – 8 ▪ Streptococcal pharyngitis Rapid strep test – Immunoassay technology – Highly specific for S. pyogenes 34 Upper Respiratory Tract Bacterial Infections – 9 ▪ Streptococcal sequelae Pathological conditions result after a primary disease has run its course. Sequelae from streptococcal infections – Caused by the immune response to the bacteria Antibodies cross-react with host cells in an autoimmune reaction, resulting in serious sequelae. 35 Upper Respiratory Tract Bacterial Infections – 10 ▪ Post-streptococcal sequelae include Acute rheumatic fever (ARF) – Young children, 4–9 years of age – High fever – Damage to heart, joints, skin, or nervous system – Cross reactive antibodies, T cells, and complement Glomerulonephritis (a kidney disease) 36 Case History: The “Bull Neck” – 1 ▪ Ramona, a 23-year-old Hispanic mother, brought her 3-year-old daughter into the emergency department. The child was lethargic, had a fever of 40°C (104°F), and was having trouble breathing. The mother explained that the family arrived in the United States from El Salvador the previous week. The attending physician noted an extreme swelling of the child’s cervical lymph nodes, giving the girl a thick “bull neck” appearance. 37 Case History: The “Bull Neck” – 2 ▪ She also noticed the beginnings of a membranous growth at the back of the child’s throat that was beginning to obstruct the trachea. It was grayish in color and bled when scraped. The distraught mother admitted that the child had not received any vaccinations before arriving in New Mexico. 38 Case History: The “Bull Neck” – 3 ▪ Suspecting the nature of the child’s illness, the physician immediately admitted the child to the hospital and ordered administration of penicillin and a specific antitoxin. The culture results of a throat swab sent to the microbiology lab confirmed the physician’s suspicion. The root of the child’s disease was Corynebacterium diphtheriae, which causes diphtheria. 39 Reemerging Upper Respiratory Tract Infections – 1 ▪ Diphtheria Corynebacterium diphtheriae Gram-positive rod Antibiotics and antitoxin are simultaneously used. Vaccine is inactivated diphtheria toxin. – Diphtheria vaccine is part of the DTaP series of vaccinations. 40 Reemerging Upper Respiratory Tract Infections – 2 ▪ Whooping cough Highly contagious Gram-negative bacillus Bordetella pertussis Acquired by inhalation of aerosolized droplets coughed by someone with the illness Incubation period of 7–21 days. The disease progresses through – Catarrhal: symptoms of upper respiratory infection – Paroxysmal: violent paroxysmal (rapidly repeated) cough, followed by a struggling deep breath that makes a whooping noise – Convalescent: paroxysms gradually disappear during the next 2–3 weeks as patient recovers 41 Reemerging Upper Respiratory Tract Infections – 3 42 Lower Respiratory Tract Bacterial Infections – 1 ▪ Bronchitis Inflammation of the bronchi Acute and self-limiting Multiple viral and bacterial etiologies Productive cough is generally the only presenting symptom. – Acute bronchitis is suspected when the patient’s cough persists for more than 5 days. 43 Lower Respiratory Tract Bacterial Infections – 2 ▪ Community acquired pneumonia Acquired outside of a hospital Pneumonia: an infection that causes inflammation in the lung Classified as typical or atypical – Atypical pneumonias affect multiple organ systems, usually produce a normal WBC count, and produce symptoms that appear gradually, mimicking upper respiratory infections at the onset. – Caused by organisms such as Mycoplasma pneumoniae, Legionella, and Chlamydophila Most common cause of typical pneumonia are organisms such as Streptococcus pneumoniae. 44 Lower Respiratory Tract Bacterial Infections – 3 45 Case History: Night Sweats in a Nursing Home – 1 ▪ In March, James, an 80-year-old resident of a New Jersey nursing home, had a fever accompanied by a productive cough with brown sputum. ▪ James reported to the attending physician that he was short of breath, had pain on the right side of his chest, and suffered from night sweats. Blood tests revealed that his white blood cell count was 14,000/µl (normal value 4,500–10,000), composed of 77% segmented forms (polymorphonuclear leukocytes, PMNs; normal value 40–60%) and 20% bands (immature PMNs; normal value 0–3%). 46 Case History: Night Sweats in a Nursing Home – 2 ▪ The chest radiograph revealed a right upper lobe infiltrate. From this information, the clinician made a diagnosis of pneumonia. Microscopic examination of the patient’s sputum revealed Gram-positive cocci surrounded by a capsule in pairs and short chains. Bacteriological culture of his sputum and blood yielded Streptococcus pneumoniae. 47 Case History: Night Sweats in a Nursing Home – 3 ▪ Streptococcus pneumoniae ▪ Occurs mostly among the elderly, smokers, and immunocompromised individuals (such as diabetics and alcoholics) ▪ There are 91 serotypes of S. pneumoniae that frequently colonize our airways. ▪ Humans are the only natural reservoir. ▪ Pneumococcal polysaccharide vaccine (PPSV) ▪ Protection against 23 of the more than 90 most prevalent polysaccharide types 48 Lower Respiratory Tract Bacterial Infections – 4 ▪ Mycoplasma pneumoniae Atypical pneumonia Mycoplasma lack a rigid cell wall and usually exist in filamentous form. Smallest known species of bacteria Symptoms include – Headache – Malaise – Progression to a nonproductive cough – Possible low-grade fever – Chills 49 Lower Respiratory Tract Bacterial Infections – 5 ▪ Legionellosis (legionnaire’s disease) Legionella pneumophila Aerobic, Gram-negative bacterium Causes atypical pneumonia L. pneumophila contaminates various water sources, ranging from lakes to the hot-water and air-conditioning distribution systems of large buildings. – Transmission via inhalation of contaminated water droplets Intracellular pathogen – After phagocytosis, the bacterium prevents the fusion of the phagosome with the lysosome. 50 Lower Respiratory Tract Bacterial Infections – 6 ▪ Hospital acquired pneumonia HAI or health care–associated infections are acquired during the course of receiving health care treatment for other conditions. Pseudomonas aeruginosa is the most common cause of hospital acquired pneumonia – Opportunistic, Gram-negative pathogen – Large number of virulence factors – Major contributor to pneumonia and mortality in patients with cystic fibrosis (CF) 51 Lower Respiratory Tract Bacterial Infections – 7 ▪ Tuberculosis Mycobacterium tuberculosis Acid-fast Cases are on the rise in developed nations due to HIV and a growing indigent population. Multidrug resistant (MDR) tuberculosis – Produces rapid onset (fulminant) and fatal disease among patients with HIV – Highly infectious even to healthy people without HIV Spread from person to person (no animal reservoir) – Aerosolizing of respiratory secretions 52 Lower Respiratory Tract Bacterial Infections – 8 ▪ Tuberculosis pathogenesis Bacteria enter lung, are phagocytized by macrophages, and survive sheltered within modified phagolysosomes. A delayed-type hypersensitivity reaction develops. – Small, hard tubercules (granulomas) form around the site of the infection. – Tubercules develop into caseous lesions that have a cheese-like consistency and can calcify into hardened Ghon complexes seen on X-rays. Latent tuberculosis: bacilli contained by immune system – Not infectious Primary disease: characterized by a productive cough that generates sputum, fever, night sweats, and weight loss – These patients have active TB and are contagious. 53 Lower Respiratory Tract Bacterial Infections – 9 54 Lower Respiratory Tract Bacterial Infections – 10 55 Pneumonia Caused by Select Agents ▪ Bacillus anthracis ▪ Inhalation anthrax Spores are inhaled if aerosolized. Prodromal phase lasts 5 days. Some may have additional symptoms of hemoptysis (coughing up blood), dyspnea (shortness of breath), chest pain, and nausea. ▪ Transmission does not usually occur from person to person. ▪ Rapid diagnosis and antibiotic treatment is critical, as death can occur within 48 hours. 56 20.4 Fungal and Parasitic Infections of the Respiratory Tract – 1 Section Objectives ▪ Identify the most common etiologies of fungal lower respiratory tract infections. ▪ Describe the difference between fungal and bacterial lower respiratory tract infections. ▪ Name the risk factors associated with fungal respiratory tract infections. 57 Case History: A Boxer’s Fight to Survive – 1 ▪ Tyrrell, a 35-year-old male boxer who installs home insulation for a living, was recently admitted to a Maryland hospital when he presented at the emergency department complaining of difficulty walking, fever, chills, night sweats, and a recent 10 kg (21 lb) weight loss. He denied having prior pneumonia, sinus infection, arthritis, hematuria (blood in urine), numbness, or muscle weakness. Tyrell also denied any history of intravenous drug use and reported to be in a monogamous relationship for the past 4 years. 58 Case History: A Boxer’s Fight to Survive – 2 ▪ There was no history of travel outside the area for the past year. A review of Tyrell’s past medical history showed that he had visited the emergency department 6 months earlier with flu-like symptoms, a chronic cough that produced blood-tinged white sputum, shortness of breath, loss of appetite, and weight loss. One month prior to current admission, he developed some painless subcutaneous nodules and became so short of breath that he could no longer continue boxing. 59 Case History: A Boxer’s Fight to Survive – 3 ▪ At that time, an X-ray taken in the emergency department showed right upper lobe infiltrate, indicating pneumonia. A tuberculosis skin test was negative. He was given a prescription for the antibiotic azithromycin (a commonly used antibiotic to treat bacterial infections of the respiratory tract) and discharged. The cough and weight loss continued. ▪ Physical exam at the time of current admission revealed several painful subcutaneous nodules, one filled with pus, and a tender tibia that prevented him from walking. A CBC obtained at the time of current admission showed normal counts and differential. 60 Case History: A Boxer’s Fight to Survive – 4 ▪ Fungal infections of the respiratory tract present with a constellation of vague and seemingly unrelated symptoms. ▪ The most likely fungal cause of infection in this case are the endemic mycoses such as histoplasmosis, blastomycosis, coccidioidomycosis, and cryptococcosis. ▪ Taking into account Tyrrell’s signs, symptoms, and history, blastomycosis, caused by Blastomyces dermatitidis, seems the most likely. ▪ Amphotericin B (antifungal) was given, and fever and skin nodules diminished. 61 20.4 Fungal and Parasitic Infections of the Respiratory Tract – 2 ▪ The portal of entry is the respiratory tract. ▪ Infection is usually associated with occupational and recreational activities in wooded areas along waterways, where there is moist soil and spores. ▪ Fungal infections are acquired from the environment and not person to person. 62 20.4 Fungal and Parasitic Infections of the Respiratory Tract – 3 ▪ Fungal infections Coccidioidomycosis – Coccidioides immitis – Endemic in the United States, Valley Fever Histoplasmosis – Histoplasma capsulatum – Flu-like illness, erythema nodosum, arthritis, arthralgia – In the United States, found mostly in the Ohio and Mississippi river valleys 63 20.4 Fungal and Parasitic Infections of the Respiratory Tract – 4 ▪ Fungal infections Blastomycosis – Blastomyces dermatitidis – Dimorphic fungus – Found mostly in the Ohio and Mississippi river valleys and eastern United States Cryptococcosis – Cryptococcus neoformans – Can involve skin, lungs, prostate gland, urinary tract, eyes, bones, and joints – The most prevalent clinical form is meningoencephalitis in AIDS patients. 64 Clicker Question 1 Why are sequelae common after streptococcal infections? a. Streptococcal infections result in opportunistic infection by the microbiome. b. Streptococcal infections increase the risk of secondary infection by viral pathogens. c. Streptococcal M proteins mimic human proteins and cause an autoimmune reaction. d. Streptococcal infections cause immunodeficiency. 65 Clicker Question 1 – Answer Why are sequelae common after streptococcal infections? a. Streptococcal infections result in opportunistic infection by the microbiome. b. Streptococcal infections increase the risk of secondary infection by viral pathogens. c. Streptococcal M proteins mimic human proteins and cause an autoimmune reaction. d. Streptococcal infections cause immunodeficiency. 66 Clicker Question 2 Which of the following viral infections of the respiratory tract is especially concerning for premature infants? a. rhinovirus b. Bordetella pertussis c. respiratory syncytial virus (RSV) d. otitis media e. Pseudomonas aeruginosa 67 Clicker Question 2 – Answer Which of the following viral infections of the respiratory tract is especially concerning for premature infants? a. rhinovirus b. Bordetella pertussis c. respiratory syncytial virus (RSV) d. otitis media e. Pseudomonas aeruginosa 68 Clicker Question 3 A patient presents with atypical pneumonia, experiencing shortness of breath, cough, and fever. The patient recently attended a party with a large indoor water fountain. Several other attendees are also ill. What is the likely cause? a. Mycoplasma pneumoniae b. Legionella pneumoniae c. Chlamydophila d. Streptococcus pneumoniae e. Pseudomonas aeruginosa 69 Clicker Question 3 – Answer A patient presents with atypical pneumonia, experiencing shortness of breath, cough, and fever. The patient recently attended a party with a large indoor water fountain. Several other attendees are also ill. What is the likely cause? a. Mycoplasma pneumoniae b. Legionella pneumoniae c. Chlamydophila d. Streptococcus pneumoniae e. Pseudomonas aeruginosa 70 This concludes the Lecture PowerPoint presentation for Chapter 20. For more resources, please visit https://stg-iig.wwnorton.com/michum2/full