Microbiology: Respiratory System Infections PDF

Microbiology: Basic and Clinical Principles Second Edition Chapter 16 Respiratory System Infections Presented by...

Microbiology: Basic and Clinical Principles Second Edition Chapter 16 Respiratory System Infections Presented by Janet Dowding, Ph.D. St. Petersburg College Copyright © 2023 Pearson Education, Inc. All Rights Reserved Clinical Case Copyright © 2023 Pearson Education, Inc. All Rights Reserved Overview of the Respiratory System After reading this section, you should be able to: Describe the parts of the upper and lower divisions of the human respiratory system. Describe the factors that limit infection of the respiratory system. Define common terminology associated with respiratory system inflammation and infections State where normal flora is found in the respiratory system and name examples of respiratory flora. Copyright © 2023 Pearson Education, Inc. All Rights Reserved The Respiratory System is the Most Common Portal of Entry for Microbes (1 of 3) Respiratory system – Brings oxygen into the body – Removes carbon dioxide Respiratory route is the most common microbial portal of entry – Impact and destination varies by pathogen Copyright © 2023 Pearson Education, Inc. All Rights Reserved The Respiratory System is the Most Common Portal of Entry for Microbes (2 of 3) The respiratory tract is divided into two parts: – Upper respiratory tract ▪ Mouth, nasal passages, paranasal sinuses, pharynx, and epiglottis ▪ Warms, humidifies, and filters air – Lower respiratory tract ▪ Larynx, trachea, bronchi, bronchioles, lungs, and alveoli ▪ Directs air to the lungs (site of gas exchange) Copyright © 2023 Pearson Education, Inc. All Rights Reserved The Respiratory System is the Most Common Portal of Entry for Microbes (3 of 3) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Upper Respiratory Tract Anatomy and Related Infection Terms (1 of 6) Paranasal sinuses – Four pairs of interconnected hollow cavities lined with mucous membranes – Specialized cells and glands secrete mucus ▪ Warms and humidifies inhaled air ▪ Traps microbes and debris – Mucus forms a layer along cilia ▪ Cilia sweep the debris and mucus toward the nose and mouth Copyright © 2023 Pearson Education, Inc. All Rights Reserved Upper Respiratory Tract Anatomy and Related Infection Terms (2 of 6) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Upper Respiratory Tract Anatomy and Related Infection Terms (3 of 6) Sinusitis – Infectious agents and inhaled allergens can aggravate and inflame the sinuses and nasal passages ▪ Blocks drainage of mucus into the nose – Sinus congestion ▪ Mucus accumulates in hollow chambers ▪ Puts pressure on surrounding structures ▪ Trapped mucus can also serve as a breeding ground for bacteria Copyright © 2023 Pearson Education, Inc. All Rights Reserved Upper Respiratory Tract Anatomy and Related Infection Terms (4 of 6) American Academy of Family Physicians estimates 15– 20% of all antibiotic prescriptions in outpatient care are prescribed to treat sinusitis But the most common cause is not bacteria, but viruses and inhaled allergens – Not treatable with antibiotics Copyright © 2023 Pearson Education, Inc. All Rights Reserved Upper Respiratory Tract Anatomy and Related Infection Terms (5 of 6) Pharynx – End of the upper respiratory tract – Gatekeeper between the respiratory and digestive tracts Pharyngitis – Inflammation of the pharynx caused by bacteria, viruses, or allergens Copyright © 2023 Pearson Education, Inc. All Rights Reserved Upper Respiratory Tract Anatomy and Related Infection Terms (6 of 6) Epiglottis – Cartilage structure – Seals off the airway during swallowing – Prevents food and drinks from entering lungs Epiglottitis – Inflammation and swelling of the epiglottis, which can block the airway – Medical emergency caused by certain infections (e.g., Haemophilus influenzae type b) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Clinical Vocabulary (1 of 7) Sinusitis: inflammation and swelling of the sinus membranes Pharyngitis: inflammation of the pharynx (throat) Epiglottitis: inflammation and swelling of the epiglottis; can quickly block the airway Copyright © 2023 Pearson Education, Inc. All Rights Reserved Lower Respiratory Tract Anatomy and Related Infection Terms (1 of 6) Mucociliary escalator – Ciliated mucous membranes lining the lower respiratory tract – Trap inhaled debris and sweep it toward the mouth to prevent it from entering the lungs Alveolar macrophages – Reside in the alveoli (air sacs) of the lungs – Clear out debris and pathogens not trapped by the mucociliary escalator Copyright © 2023 Pearson Education, Inc. All Rights Reserved Lower Respiratory Tract Anatomy and Related Infection Terms (2 of 6) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Lower Respiratory Tract Anatomy and Related Infection Terms (3 of 6) Inhaled allergens and microbes can cause inflammation of lower respiratory tract tissues Laryngitis – Inflammation of the larynx – Can cause temporary voice loss due to the swelling of the vocal cords Tracheitis – Inflammation of the trachea Copyright © 2023 Pearson Education, Inc. All Rights Reserved Lower Respiratory Tract Anatomy and Related Infection Terms (4 of 6) Bronchitis – Inflammation of the bronchi and/or bronchioles Croup (laryngotracheobronchitis) – Combined inflammation of the larynx, trachea, bronchi, and bronchioles – Viruses cause most croup cases – Characterized by a barking cough and respiratory stridor Copyright © 2023 Pearson Education, Inc. All Rights Reserved Lower Respiratory Tract Anatomy and Related Infection Terms (5 of 6) Pneumonia – Inflammation of the lung tissue – Can upset the delicate oxygen balance required by the body – Can become life-threatening Copyright © 2023 Pearson Education, Inc. All Rights Reserved Lower Respiratory Tract Anatomy and Related Infection Terms (6 of 6) Signs and symptoms of respiratory infections often include one or more of the following: – Coughing – Stridor – Dyspnea (shortness of breath) – Fatigue – Sneezing – Sore throat – Fever Copyright © 2023 Pearson Education, Inc. All Rights Reserved Clinical Vocabulary (2 of 7) Laryngitis: inflammation and swelling of the larynx; can cause temporary voice loss Tracheitis: inflammation and swelling of the trachea Bronchitis: inflammation and swelling of the bronchi and/or bronchioles Croup: laryngotracheobronchitis (combined inflammation of the larynx, trachea, bronchi, and bronchioles) caused mainly by viruses; characterized by a barking cough and stridor Copyright © 2023 Pearson Education, Inc. All Rights Reserved Clinical Vocabulary (3 of 7) Stridor: wheezing or loud breathing associated with a blocked or narrowed airway Pneumonia: inflammation of the alveoli, which are the small air sacs in the lungs where gas exchange occurs Dyspnea: shortness of breath Copyright © 2023 Pearson Education, Inc. All Rights Reserved Respiratory Tract Microbiome (1 of 5) Many microorganisms colonize the respiratory tract Healthy lungs were previously thought to be a sterile environment – Numerous studies have shown the lungs are colonized by normal microbiota – Microbial profiles resemble what is found in the mouth Copyright © 2023 Pearson Education, Inc. All Rights Reserved Respiratory Tract Microbiome (2 of 5) Resident microbiota are typically more helpful than harmful – Compete with potential pathogens – Some secrete antimicrobial peptides to limit the growth of would-be pathogens Copyright © 2023 Pearson Education, Inc. All Rights Reserved Respiratory Tract Microbiome (3 of 5) Normal microbiota profiles in the respiratory tract vary between: – Individuals – People with healthy lungs and those with underlying health issues (e.g., asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and lung cancer) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Respiratory Tract Microbiome (4 of 5) Healthy respiratory microbiome – Has a high diversity of species – Mainly dominated by bacteria from the phyla Bacteroides, Firmicutes, Actinobacteria, Proteobacteria, and Fusobacteria Copyright © 2023 Pearson Education, Inc. All Rights Reserved Respiratory Tract Microbiome (5 of 5) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Viral Infections of the Respiratory System (1 of 3) After reading this section, you should be able to: Compare and contrast the symptoms of colds and influenza. List special clinical features of illnesses caused by respiratory syncytial virus, human parainfluenza viruses, and adenoviruses. Discuss how antigenic shift and antigenic drift affect viral evolution and state the likely role of antigenic shift in the development of the influenza pandemic of 1918 (i.e., the “Spanish flu” pandemic). Copyright © 2023 Pearson Education, Inc. All Rights Reserved Viral Infections of the Respiratory System (2 of 3) After reading this section, you should be able to: Discuss characteristics of SARS-CoV-2, including how it is transmitted, how it invades host cells, and features of COVID-19––the disease it causes. Define the terms viral variant and viral strain and discuss the three categories used to group SARS-CoV- 2 variants. Describe what hanta pulmonary syndrome is and how it is transmitted. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Viral Infections of the Respiratory System (3 of 3) Hundreds of different viruses can infect the respiratory tract General symptoms of viral respiratory illnesses overlap Severity and the prognosis depend on: – Infectious agent – Patient factors (e.g., age, general health) Vaccines are available for some viral respiratory illnesses Copyright © 2023 Pearson Education, Inc. All Rights Reserved Colds are the Most Common Cause of Respiratory Infections (1 of 6) Common cold is clinically known as an acute respiratory infection (ARI) Most common infections of the respiratory system There are >200 genetically distinct viruses from  8 different genera that cause the common cold Usually self-limiting Copyright © 2023 Pearson Education, Inc. All Rights Reserved Colds are the Most Common Cause of Respiratory Infections (2 of 6) Have a huge economic impact – Lost productivity – Healthcare expenditures Copyright © 2023 Pearson Education, Inc. All Rights Reserved Colds are the Most Common Cause of Respiratory Infections (3 of 6) Serovars of rhinoviruses and coronaviruses cause 60– 80% all colds Other viruses that cause colds include: – Parainfluenza viruses – Adenoviruses – Nonpolio-type enteroviruses (common in warmer months) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Colds are the Most Common Cause of Respiratory Infections (4 of 6) Cold viruses are highly infectious Spread through: – Personal contact – Respiratory droplets expelled during coughs and sneezes – Fomites (e.g., doorknobs, cell phones, pacifiers) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Colds are the Most Common Cause of Respiratory Infections (5 of 6) Symptoms of the common cold can include: – Sudden onset of sore throat – Runny nose – Coughing and/or sneezing – Fatigue – General body achiness – Loss of appetite – Low-grade fever (common in children) – Thickened and discolored mucus in later stages Copyright © 2023 Pearson Education, Inc. All Rights Reserved Colds are the Most Common Cause of Respiratory Infections (6 of 6) Adults average  3 colds per year Children average  6 colds per year About 1 in 200 colds result in a secondary bacterial infection May progress to a sinus infection, ear infection, or a lower respiratory tract infection Antibiotics are usually prescribed if symptoms persist for >10 days without improvement Copyright © 2023 Pearson Education, Inc. All Rights Reserved Respiratory Syncytial Virus (RSV) Infections (1 of 3) Respiratory syncytial virus (RSV) infections Etiological agent – Enveloped RNA virus – Paramyxoviridae family – Main RSV subtypes: A and B Copyright © 2023 Pearson Education, Inc. All Rights Reserved Respiratory Syncytial Virus (RSV) Infections (2 of 3) Characteristics – In the elderly and in infants RSV can be quite serious – Leading cause of acute lower respiratory tract infection in children under 5 worldwide – Top cause of bronchitis and pneumonia in children under 1-year-old – Almost all children have battled this virus before their second birthday – Globally, estimated 33 million cases, 3 million hospitalizations, and 66,000 deaths per year Copyright © 2023 Pearson Education, Inc. All Rights Reserved Respiratory Syncytial Virus (RSV) Infections (3 of 3) Prevention – Vaccine is in clinical trials – Expensive antibody preparations can be given to high-risk patients ▪ Cons: expensive and requires monthly injections Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Respiratory Syncytial Virus (RSV) Causative agent Respiratory syncytial virus (RSV): enveloped, single-stranded RNA genome, Pneumoviridae family Epidemiology Endemic among children under age 5; can be dangerous in premature infants and in patients who are immune compromised or suffer from chronic lung and/or heart conditions; most cases occur from fall through early spring; incubation period is usually 4–6 days Transmission & Transmitted by respiratory droplets and fomites; typical preventions are sanitary practices and hand washing; antibody prevention injections for high-risk groups (especially premature infants) Signs & symptoms Coughing, sneezing, and fever are typical symptoms; wheezing may also occur Pathogenesis & Enters the upper respiratory tract and spreads to the lower respiratory tract within 1–3 days, causing inflammation in the virulence factors airways; masses of multinucleated cell bodies, called syncytia, form; immune system cells can damage epithelial cells in the airway and contribute to pathology Diagnosis & Antigen-detection tests are commonly used for diagnosis; supportive therapies alleviate symptoms; aerosolized antiviral treatment drug ribavirin may be administered in severe cases Copyright © 2023 Pearson Education, Inc. All Rights Reserved Human Parainfluenza Virus (HPIV) Infections (1 of 4) Human parainfluenza virus (HPIV) infections Etiological agent – Single-stranded RNA viruses – Paramyxoviridae family – Genetically and clinically different from influenza viruses – Four types of HPIV Copyright © 2023 Pearson Education, Inc. All Rights Reserved Human Parainfluenza Virus (HPIV) Infections (2 of 4) Characteristics – Responsible for up to 30% of respiratory infections in children under age 5 Transmission – Respiratory droplets and fomites – Cause infections in fall, spring, and summer Copyright © 2023 Pearson Education, Inc. All Rights Reserved Human Parainfluenza Virus (HPIV) Infections (3 of 4) Signs and symptoms – Cold-like symptoms in adults – More severe illnesses in infants and elderly ▪ Croup, bronchitis, and pneumonia – HPIV-1 and HPIV-2 are the most common causes of croup in children – HPIV-3 tends to cause bronchiolitis, bronchitis, and pneumonia – HPIV-4 causes mild cold-like symptoms Copyright © 2023 Pearson Education, Inc. All Rights Reserved Human Parainfluenza Virus (HPIV) Infections (4 of 4) Complications – In developing nations considerable risk for death in normally healthy preschool-age children Treatment – Supportive therapies Prevention – Vaccine in clinical trials Copyright © 2023 Pearson Education, Inc. All Rights Reserved Adenovirus Infections (1 of 3) Adenovirus infections Etiological agent – Nonenveloped DNA viruses – >50 types of adenoviruses can infect humans Characteristics – Cause up to 10% of respiratory illnesses in children Copyright © 2023 Pearson Education, Inc. All Rights Reserved Adenovirus Infections (2 of 3) Signs and symptoms – Attack the respiratory tract – Sore throat and cold-like symptoms Complications – Certain adenoviruses cause viral conjunctivitis, gastroenteritis, and cystitis – Bronchitis, pneumonia, and croup – Occasionally cause potentially deadly infections Copyright © 2023 Pearson Education, Inc. All Rights Reserved Adenovirus Infections (3 of 3) Prevention – Vaccine against adenovirus types 4 and 7 given to military in the United States Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Adenovirus Infections Causative agent Over 50 types of adenoviruses; most cause respiratory illnesses, others cause conjunctivitis, diarrhea, and cystitis: nonenveloped, double-stranded DNA genome, Adenoviridae family Epidemiology Endemic in populations worldwide, human reservoir; infections occur year-round, but outbreaks are more common in late winter through early summer; incubation period is usually 2–10 days Transmission & Respiratory droplets and fomites for types that target the respiratory tract; vaccine against types 4 and 7 approved prevention for military personnel only; sanitary practices and hand washing are most common prevention methods Signs & symptoms Most adenoviruses attack the respiratory tract and cause sore throat and cold-like symptoms, but occasionally they cause more severe and potentially deadly infections of the respiratory tract, including bronchitis, viral pneumonia, and croup Pathogenesis & Attach to host cells and are engulfed by endocytosis; as the viral load increases, the production of host cell RNA virulence factors and proteins kills the cell; make a special viral-associated RNA (VA RNA) that prevents the host cell from mounting a defense against the virus Diagnosis & treatment Usually identified using antigen detection or polymerase chain reaction; supportive therapies to alleviate symptoms Copyright © 2023 Pearson Education, Inc. All Rights Reserved Influenza is Among the Most Common Viral Respiratory Illnesses in Humans (1 of 3) Influenza (“the flu”) Signs and symptoms – Resemble a severe cold Mechanism of disease – Most strains bind to ciliated cells in the upper respiratory tract – Some strains can directly affect the lungs Copyright © 2023 Pearson Education, Inc. All Rights Reserved Influenza is Among the Most Common Viral Respiratory Illnesses in Humans (2 of 3) Complications – Pneumonia – Can be deadly in those with pre-existing conditions Copyright © 2023 Pearson Education, Inc. All Rights Reserved Influenza is Among the Most Common Viral Respiratory Illnesses in Humans (3 of 3) Disease and death rates vary from year to year, depending on the strains circulating – 2011–2012 season ▪ Mild season ▪ 12,000 deaths – 2017–2018 season ▪ 61,000 deaths in the United States ▪ Millions of deaths worldwide Copyright © 2023 Pearson Education, Inc. All Rights Reserved Types of Influenza Viruses (1 of 6) There are three related types of influenza viruses that can infect humans: – Type A – Type B – Type C Copyright © 2023 Pearson Education, Inc. All Rights Reserved Types of Influenza Viruses (2 of 6) Type A influenza – Most common cause of human flu epidemics Type B influenza – Less impactful, but still causes epidemics CDC found nearly three times as many deaths occur during flu season when type A influenza strains are prominent Copyright © 2023 Pearson Education, Inc. All Rights Reserved Types of Influenza Viruses (3 of 6) Influenza’s hemagglutinin (HA) and neuraminidase (NA) are important virulence factors – HA and NA are glycoprotein spikes on the surface of the influenza virus ▪ HA allows influenza to attach and invade target cells in the respiratory tract ▪ NA helps newly formed viral particles escape the host cell Copyright © 2023 Pearson Education, Inc. All Rights Reserved Types of Influenza Viruses (4 of 6) HA and NA subtypes are numbered and used to name and group influenza type A viruses – 18 different subtypes of the HA protein – 10 distinct variants of the NA protein –  170 influenza A subtypes Copyright © 2023 Pearson Education, Inc. All Rights Reserved Types of Influenza Viruses (5 of 6) Some strains gained the ability to invade human cells by changing their HA and NA proteins: – Swine flu (H1N1) – Avian or “bird” flu (H5N1 and H7N9) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Types of Influenza Viruses (6 of 6) Emergence of new strains in not uncommon because: – Influenza’s RNA genome mutates quickly – Ability to genetically mix-and-match RNA segments Copyright © 2023 Pearson Education, Inc. All Rights Reserved Seasonal Outbreaks Versus Worldwide Pandemics (1 of 2) Antigenic drift – Random mutations – Cause minor changes of HA and NA spikes – Allows evasion of the immune system Antigenic shift – Major genetic change – Causes major alterations in viral antigens – Can allow for pandemics Copyright © 2023 Pearson Education, Inc. All Rights Reserved Seasonal Outbreaks Versus Worldwide Pandemics (2 of 2) Spanish influenza pandemic of 1918 – 8 million people died in Spain in one month – Highest mortality rate in 15–34 year olds ▪ Cytokine storms caused aggressive and out-of- control immune responses Copyright © 2023 Pearson Education, Inc. All Rights Reserved Influenza Vaccines (1 of 4) Flu vaccines are the best option to prevent and limit influenza New flu vaccines are created every year – Based on strains the World Health Organization (WHO) believes will most likely be circulating widely in the next season Since the viral candidates change from year to year, people must get vaccinated every year Copyright © 2023 Pearson Education, Inc. All Rights Reserved Influenza Vaccines (2 of 4) Three main influenza vaccine types available Inactivated formulations – Injectable vaccines – Contain at least three inactivated viruses Recombinant preparations – Contain purified parts of the virus Live attenuated – Contained at least 4 different, active but weakened viruses Copyright © 2023 Pearson Education, Inc. All Rights Reserved Influenza Vaccines (3 of 4) From a public health standpoint, it is important to vaccinate a significant portion of the population Provides herd immunity – Benefits at-risk groups – Limits circulation and thereby directly reduces the opportunity for the virus to mutate Copyright © 2023 Pearson Education, Inc. All Rights Reserved Influenza Vaccines (4 of 4) Vaccine myths and reality – “I got the flu from the vaccine” ▪ False: The inactivated influenza vaccine does not contain active viral particles – “I got the flu shot and still caught the flu” ▪ Plausible: An educated guess is made on which strains will be circulating Vaccine provides a 60% reduced risk of influenza illness across the overall population when correct strains are predicted Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Influenza Causative agent Influenza types A, B, and C (type A strains are the major concern in epidemics and pandemics): enveloped, single-stranded RNA genome, Orthomyxoviridae family Epidemiology Endemic, with ability to cause epidemics and pandemics; exhibits seasonality with most infections in late fall through early spring; 1- to 4-day incubation period Transmission & prevention Respiratory droplets and fomites; prevented by seasonal vaccines, sanitary practices, and hand washing Signs & symptoms Symptoms tend to be similar to those of a severe cold; especially fever, chills, and body aches. Severe complications like pneumonia can occur. Pathogenesis & NS1 protein helps type A viruses dodge antiviral response of host cells through interferon; HA proteins impact virulence factors how effectively the virus can invade cells; NA proteins help the virus escape host cells to infect more host cells Diagnosis & treatment Rapid immunoassays detecting either influenza A or B are routinely used for diagnosis; in high-risk patients, antivirals may be used to treat infections. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Novel Coronaviruses Include SARS-CoV- 2, the Cause of COVID-19 Coronaviruses large and diverse family of enveloped RNA viruses 2003 outbreak: Severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) 2012 outbreak: Middle East Respiratory Syndrome (MERS-CoV) 2019 outbreak: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) – Coronavirus disease 2019 (COVID-19) Copyright © 2023 Pearson Education, Inc. All Rights Reserved SARS-CoV-2 Pathophysiology (1 of 2) SARS-CoV-2 – Single-stranded RNA genome – Encodes 29 proteins ▪ RNA-dependent RNA polymerase ▪ Spike proteins (S proteins) Copyright © 2023 Pearson Education, Inc. All Rights Reserved SARS-CoV-2 Pathophysiology (2 of 2) Mechanism of disease – Spreads via respiratory droplets and aerosols – Binds to ACE2 on host cells – Symptoms can develop within 2 to 14 days – Degree of disease severity varies greatly by patient factors and underlying conditions – COVID-19 kills patients due to a sudden and marked reduction in blood oxygenation: Acute respiratory distress syndrome (ARDS) Copyright © 2023 Pearson Education, Inc. All Rights Reserved SARS-CoV-2 Variants and Strains (1 of 2) RNA viruses tend to mutate more frequently than DNA viruses leading to a viral variant If viral functions are altered, the variant is a new viral strain Emerging SARS-CoV-2 variants are categorized by the risk: – Variants of interest – Variants of concern – Variants of high consequence Copyright © 2023 Pearson Education, Inc. All Rights Reserved SARS-CoV-2 Variants and Strains (2 of 2) Table 16.1 Categorical Classification of SARS-CoV-2 Variants Category Examples of Variant’s Attributes Examples of Public Health Actions Variants of Predicted to affect transmission, reduce Enhanced sequence surveillance Interest efficacy of diagnostics, therapeutics, or Enhanced laboratory characterization promote evasion of vaccine-induced immunity Continued evaluation of transmission Linked to increased number of cases/new features, efficacy of existing vaccines and outbreak clusters therapeutics against the variant, and Limited circulation disease severity linked to the variant Variants of Some evidence of reduced efficacy of existing Notify WHO Concern diagnostics, treatments, and/or vaccines Enhanced testing for the variant to facilitate Some evidence of increased transmissibility tracking and reporting of cases caused by Some evidence of increased disease severity the variant to control spread Additional research to assess efficacy of existing vaccines and therapeutics against the variant Research and develop new vaccines and therapeutics that are effective against the variant Variants of Significant reduction in efficacy of existing Notify WHO High diagnostics, treatments, and/or vaccines Announce strategies to prevent or contain Consequence Clear evidence of increased transmissibility transmission Clear evidence of increased disease severity Recommend treatment and vaccine updates Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Coronavirus Disease (COVID-19) (1 of 2) Causative agent Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2): enveloped, single-stranded RN A genome, Coronaviridae family Epidemiology Originated in Wuhan China late 2019; affects people of all ages, though children are less likely to become severely ill; case fatality rate varies, with older patients and patients with underlying conditions having a higher mortality rate—worldwide the average case fatality rate is about 2%; incubation period of 2–14 days; percentage of asymptomatic cases varies greatly by age and other patient factors, but pooled data suggest that about 16% of infections are asymptomatic* Transmission & Transmitted by respiratory droplets and aerosols; COVID-19 vaccines are available as an prevention effective prevention against severe COVID-19 (see Chapter 14 for details) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Coronavirus Disease (COVID-19) (2 of 2) Signs & symptoms Characterized by flu-like signs and symptoms, including one or more of the following: fever, chills, cough, shortness of breath, body aches, fatigue, headache, loss of smell (anosmia), sore throat, nausea or vomiting, diarrhea, congestion or runny nose. Emergency care should be sought if any of the following develop: trouble breathing, persistent pain or pressure in the chest, difficulty with waking or staying awake, confusion (new or abnormal for the patient), pale/gray/or blue-colored skin, lips, or nail beds Pathogenesis & Can trigger an exaggerated inflammatory immune response and cytokine storm; broad virulence factors tissue tropism can lead to systemic failure likely because of dysregulated ACE2/ANGII function Diagnosis & treatment RT-PCR to detect viral RNA remains the gold standard for diagnosis; rapid tests for viral antigen detection are also available; remdesivir (inhibitor of viral RNA polymerase) is FD A-approved for treating hospitalized COVID-19 patients ages 12 and older who weigh at least 40 kg; dexamethasone may also decrease mortality, with the largest benefit seen among patients receiving invasive mechanical ventilation He, J., Guo, Y., Mao, R., & Zhang, J. (2021). Proportion of asymptomatic coronavirus disease 2019: A systematic review and meta-analysis. Journal of Medical Virology, 93(2), 820–830. *Based on 50,155 confirmed COVID-19 patients from 41 studies. The percentage of asymptomatic cases varies greatly by age and even by study. Based on pooled data, about 27% of confirmed COVID-19 cases in children were described as asymptomatic. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Hantavirus Pulmonary Syndrome is a Rare but Dangerous Illness (1 of 4) Hanta pulmonary syndrome (HPS) Etiological agent – >40 known viruses in the genus Hantavirus ▪  25 hantaviruses located throughout North and South America can cause HPS ▪ Others cause hemorrhagic fever with renal syndrome (HFRS) Characteristics – Acute and potentially fatal respiratory illness Copyright © 2023 Pearson Education, Inc. All Rights Reserved Hantavirus Pulmonary Syndrome is a Rare but Dangerous Illness (2 of 4) Transmission – Inhalation of airborne dust particles containing hantavirus particles shed in rodent urine or feces – Many rodent species can carry hantaviruses – In the United States the most common rodent carrier is the deer mouse – Certain strains can be transmitted from person to person Copyright © 2023 Pearson Education, Inc. All Rights Reserved Hantavirus Pulmonary Syndrome is a Rare but Dangerous Illness (3 of 4) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Hantavirus Pulmonary Syndrome is a Rare but Dangerous Illness (4 of 4) Signs and symptoms – Initial symptoms can lead to pulmonary edema Complications – 30–40% mortality rate Copyright © 2023 Pearson Education, Inc. All Rights Reserved Bacterial Infections of the Respiratory System (1 of 3) After reading this section, you should be able to: Describe why children are prone to developing otitis media as a complication of colds. Give examples of diseases caused by Streptococcus pyogenes. Describe the pathological progression of diphtheria and how it is prevented. Describe the pathological progression of pertussis and discuss factors contributing to its reemergence. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Bacterial Infections of the Respiratory System (2 of 3) After reading this section, you should be able to: Name and describe the causative agent of tuberculosis and the forms of the disease. Give examples of organisms that cause typical pneumonia and describe their effects. Describe the features of the most common causes of atypical bacterial pneumonia: Chlamydia pneumonia, Mycoplasma pneumoniae, Legionella pneumophila, Chlamydophila psittaci, Coxiella burnetii, and Francisella tularensis. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Bacterial Infections of the Respiratory System (3 of 3) Viruses are the most common infectors of the respiratory tract as a whole Bacterial infections are also a common secondary complication of the viral infections Copyright © 2023 Pearson Education, Inc. All Rights Reserved Otitis Media is a Common Bacterial Complication of Colds (1 of 3) Otitis media Etiological agent – Streptococcus pneumoniae – Moraxella catarrhalis – Nontypable Haemophilus influenzae Characteristics – By age 2 at least 80% of children experience otitis media Copyright © 2023 Pearson Education, Inc. All Rights Reserved Otitis Media is a Common Bacterial Complication of Colds (2 of 3) Mechanism of disease – During a cold, inflamed membranes can cause mucus to accumulate – Provides an environment for bacteria to grow – Middle ear is connected to the pharynx by the eustachian tube – During a cold, the eustachian tubes can become inflamed – Blocks mucus drainage, allows for bacterial infection of the middle ear Copyright © 2023 Pearson Education, Inc. All Rights Reserved Otitis Media is a Common Bacterial Complication of Colds (3 of 3) Children are especially susceptible – Shorter and narrower eustachian tubes – Inefficient drainage Prevention – For repeat ear infections tubes are inserted to help drainage Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Otitis Media Causative agent Most commonly Streptococcus pneumoniae (primarily types not included in the pneumococcal conjugate vaccine) , Moraxella catarrhalis, and nontypable Haemophilus influenzae Epidemiology Widespread; 70% of children in the U.S. have a middle ear infection by age 3; common complication of colds and allergies; often develops 2–7 days after a cold Transmission & Noncommunicable; vaccination with pneumococcal conjugate vaccine reduces occurrence due to specific bacteria; prevention treating colds with decongestants may reduce mucus buildup in the eustachian tubes to reduce infection incidence Signs & symptoms May include earache, redness of the eardrum, leakage of pus or blood from the ear, and fever Pathogenesis & Accumulation of mucus in the eustachian tube serves as a breeding ground for bacteria; some causative bacteria have virulence factors capsules and/or fimbriae to help establish infection; disruption of normal barriers such as earwax removal through ear cleaning and tissue trauma (such as a ruptured eardrum) may promote otitis media Diagnosis & Symptomatic diagnosis includes a swelling or effusion from the tympanic membrane combined with visible membrane treatment redness and earache; amoxicillin is a drug of choice for treatment; in minor cases, decongestants to drain the ear canal and pain management are often recommended over antibiotics Copyright © 2023 Pearson Education, Inc. All Rights Reserved Streptococcus Pyogenes Primarily Causes Strep Throat (1 of 6) Streptococcus genus – Includes >40 species – Gram-positive cocci; grow in chains – Often found as normal flora of the upper respiratory tract and skin Some strains cause diseases – Endocarditis, pharyngitis, meningitis, genitourinary system infections, sepsis, dental caries, skin infections, and pneumonia Copyright © 2023 Pearson Education, Inc. All Rights Reserved Streptococcus Pyogenes Primarily Causes Strep Throat (2 of 6) Streptococcal pharyngitis (strep throat) Etiological agent – Group A streptococcus (GAS) S. pyogenes Characteristics – Causes acute pharyngitis in: ▪ Up to 15% of adults ▪ Up to 30% of children Copyright © 2023 Pearson Education, Inc. All Rights Reserved Streptococcus Pyogenes Primarily Causes Strep Throat (3 of 6) Transmission – Many people are asymptomatic carriers – Most cases occur in winter and early spring – Transmitted by respiratory droplets Copyright © 2023 Pearson Education, Inc. All Rights Reserved Streptococcus Pyogenes Primarily Causes Strep Throat (4 of 6) Signs and symptoms – Inflammation of the throat – Swollen cervical lymph nodes – Low-grade fever – Exudate in the throat or tonsils – Cough is absent in most cases Copyright © 2023 Pearson Education, Inc. All Rights Reserved Streptococcus Pyogenes Primarily Causes Strep Throat (5 of 6) Complications – Otitis, sinusitis, invasive pneumonia Diagnosis – Rapid strep test for bacterial antigens – Culture that identifies S. pyogenes Treatment – Penicillin-based drugs – Macrolide drugs for patients allergic to penicillin (e.g., erythromycin) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Streptococcus Pyogenes Primarily Causes Strep Throat (6 of 6) Prevention – Hand washing – Avoid contact with infected patients Copyright © 2023 Pearson Education, Inc. All Rights Reserved Virulence and Pathogenesis Factors S. pyogenes has a multitude of factors that make it a dangerous pathogen Examples of factors: – Hyaluronic acid capsule ▪ Resembles human connective tissue ▪ Helps the bacteria avoid immune detection – M protein ▪ Helps with adhesion to host cells and avoiding phagocytosis Copyright © 2023 Pearson Education, Inc. All Rights Reserved Scarlet Fever (1 of 3) Scarlet fever Etiological agent – Lysogenized S. pyogenes strains – Gained the ability to produce an erythrogenic toxin Characteristics – Occurs in 100 different strains of S. pyogenes Strains can be characterized is by a cell surface virulence factor M protein Certain M proteins look a lot like proteins found in heart valves, parts of the kidney, and joints M proteins that can stimulate autoimmune complications are rheumatogenic Copyright © 2023 Pearson Education, Inc. All Rights Reserved Autoimmune Complications of S. pyogenes Infection (2 of 3) M proteins can trigger the body to make antibodies that attack S. pyogenes, but also cross-react with our own proteins Copyright © 2023 Pearson Education, Inc. All Rights Reserved Autoimmune Complications of S. pyogenes Infection (3 of 3) Rheumatic fever caused by S. pyogenes that possess rheumatogenic M proteins Transmission – Progresses from untreated strep throat Signs and symptoms – Host antibodies cause inflammation of the joints, nervous system, heart, and skin Complications – Heart complications—rheumatic heart disease Copyright © 2023 Pearson Education, Inc. All Rights Reserved Corynebacterium Diphtheriae Causes Diphtheria (1 of 5) Diphtheria Etiological agent – Corynebacterium diphtheriae – Gram-positive rod Characteristics – Commonly affects children under age 5 Transmission – Respiratory droplets Copyright © 2023 Pearson Education, Inc. All Rights Reserved Corynebacterium Diphtheriae Causes Diphtheria (2 of 5) Signs and symptoms – Cold-like symptoms – Sore throat and a low-grade fever – Cough and hoarseness – “Bull neck” – Pseudomembrane forms in the upper airway about 3 days after initial symptoms develop ▪ Formed as a result of the bacterial toxin killing off tissue in the upper airway Copyright © 2023 Pearson Education, Inc. All Rights Reserved Corynebacterium Diphtheriae Causes Diphtheria (3 of 5) Complications – Untreated cases may be fatal within a few days due to the pseudomembrane Copyright © 2023 Pearson Education, Inc. All Rights Reserved Corynebacterium Diphtheriae Causes Diphtheria (4 of 5) Complications – Some strains make A-B exotoxin ▪ May enter the bloodstream ▪ Affects protein synthesis ▪ Patient may develop: – Rapid pulse – Paleness (pallor) – Progressive weakness – Loss of consciousness and coma Copyright © 2023 Pearson Education, Inc. All Rights Reserved Corynebacterium Diphtheriae Causes Diphtheria (5 of 5) Complications of A-B exotoxin producing strains – Patients dies within 6–10 days in 10% of untreated cases and ~ 50% of untreated cases Treatment – Antibiotics – Antitoxin Prevention – DTaP vaccine (diphtheria and tetanus toxoids and acellular pertussis vaccine) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Clinical Vocabulary (4 of 7) Exudate: a fluid discharge (can be pus-like or clear fluid) that is present in a given tissue; usually produced in response to inflammation Paroxysm: a sudden and violent attack (as in a paroxysm of coughing) Convalescent: not fully better, but recovering Latent infection: the infectious agent is present, but not causing symptoms; if conditions are right, the agent can cause an active illness Copyright © 2023 Pearson Education, Inc. All Rights Reserved Clinical Vocabulary (5 of 7) Induration: the hardening of a tissue often caused by inflammation; a hardened or fibrous mass in a normally elastic and soft tissue Copyright © 2023 Pearson Education, Inc. All Rights Reserved Pertussis (Whooping Cough) is an Acute Infection of the Respiratory Tract Pertussis (whooping cough) Etiological agent – Bordetella pertussis – Gram-negative Copyright © 2023 Pearson Education, Inc. All Rights Reserved Three Stages of Pertussis (1 of 4) First phase: catarrhal phase Signs and symptoms – Cold-like symptoms (e.g., runny nose, cough) – No fever or sore throat Duration – 1–2 weeks Copyright © 2023 Pearson Education, Inc. All Rights Reserved Three Stages of Pertussis (2 of 4) Second phase: paroxysmal stage Signs and symptoms – Severe coughing attacks (paroxysms) Mechanism of disease – Toxins accumulate in the respiratory system – Pertussis toxin triggers generalized inflammation in the respiratory tract Duration – 2–6 weeks Copyright © 2023 Pearson Education, Inc. All Rights Reserved Three Stages of Pertussis (3 of 4) Complications – Severe that they may cause vomiting, fractured ribs, and loss of bladder control – In children and babies, bleeding behind the eyes and in the brain can occur Copyright © 2023 Pearson Education, Inc. All Rights Reserved Three Stages of Pertussis (4 of 4) Third phase: convalescent stage Signs and symptoms – Less frequent coughing spells Duration – ~ 4 weeks Copyright © 2023 Pearson Education, Inc. All Rights Reserved Reemergence (1 of 2) Pertussis is one of the few vaccine-preventable diseases that is currently on the rise Copyright © 2023 Pearson Education, Inc. All Rights Reserved Reemergence (2 of 2) Immunity from the routine childhood DTaP vaccine is not long lived Adolescents and adults are encouraged to get a booster shot (Tdap) Tdap highly recommended for: – Pregnant women – Childcare workers – Healthcare providers – Parents and grandparents Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Pertussis (Whooping Cough) (1 of 2) Causative agent Bordetella pertussis; Gram-negative bacterium Epidemiology Main reservoir is adults and adolescents with atypical or undiagnosed infection; highly contagious (infects 80–90% of susceptible hosts); found worldwide; reemergence due to need for a booster vaccine and newly emerging B. pertussis strains; about 1.7 million cases per year worldwide (most are not diagnosed) with about 89,000 deaths (WHO statistic from 2019; most dangerous in infants; 7–10 days average incubation period Transmission & Transmitted by respiratory droplets or direct contact; prevented by the DTaP vaccine prevention (booster vaccine recommended for adolescents, adults, and pregnant women); to limit spread, antibiotics may be given to those with close/regular contact with a diagnosed case Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Pertussis (Whooping Cough) (2 of 2) Signs & symptoms Catarrhal phase: cold-like symptoms Paroxysmal stage: intense coughing fits that leave patient gasping for air and can also induce convulsions Convalescent stage: lasts up to 3 months and is characterized by less frequent coughing spells Pathogenesis & Tracheal cytotoxin damages the ciliated cells of the mucociliary escalator, virulence factors which causes mucus to accumulate and settle in the lungs; pertussis toxin damages host airway cells and stimulates an inflammatory response Diagnosis & treatment Bacterial culture from a nasopharyngeal sample is the best diagnostic technique; serological tests to detect patient antibodies to B. pertussis and screening patient samples for bacterial DNA by PCR techniques are also used; treated with macrolide antibiotics (i.e., erythromycin, clarithromycin, or azithromycin) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Tuberculosis (TB) is One of the Top Infectious Disease Killers in the World (1 of 4) Tuberculosis (TB) Etiological agent – Mycobacterium tuberculosis – Acid-fast rod Transmission – Patients with active TB can transmit the disease to others Copyright © 2023 Pearson Education, Inc. All Rights Reserved Tuberculosis (TB) is One of the Top Infectious Disease Killers in the World (2 of 4) Characteristics – Historically known as “consumption” – TB is found throughout the world – Prevalent in Latin America, Africa, eastern Europe, and throughout Asia – Until COVID-19, worldwide TB was the leading cause of death from an infectious agent Copyright © 2023 Pearson Education, Inc. All Rights Reserved Tuberculosis (TB) is One of the Top Infectious Disease Killers in the World (3 of 4) Signs and symptoms – Most infected individuals develop an asymptomatic latent infection ▪ Not contagious Progression – Some progress to an active infection ▪ Cough with blood-tinged sputum, fever, night sweats, fatigue, and weight loss Copyright © 2023 Pearson Education, Inc. All Rights Reserved Tuberculosis (TB) is One of the Top Infectious Disease Killers in the World (4 of 4) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Vaccination and Screening (1 of 5) Bacillus Calmette-Guérin (BCG) vaccine – Live-attenuated vaccine – Available in over 157 countries ▪ Routinely given to children negative for both HIV and the tuberculin skin test – Recommended for people at high risk for TB exposure In areas such as the United States where people are not routinely vaccinated against TB, the tuberculin skin test is used to screen at-risk groups Copyright © 2023 Pearson Education, Inc. All Rights Reserved Vaccination and Screening (2 of 5) Mantoux tuberculin skin test – Performed by an intradermal injection of tuberculin purified protein derivative (PPD) into the skin of the forearm Copyright © 2023 Pearson Education, Inc. All Rights Reserved Vaccination and Screening (3 of 5) Mantoux tuberculin skin test – Injection site is inspected for induration – Induration size is measured Copyright © 2023 Pearson Education, Inc. All Rights Reserved Vaccination and Screening (4 of 5) Tuberculin skin test does not distinguish between an active versus a latent TB infection Patients who have been vaccinated against TB can have a false-positive skin test result Previously vaccinated patients should instead be tested with: – Molecular diagnostics (e.g., Xpert MTB/RIF) – Interferon gamma release assay (IGRA) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Vaccination and Screening (5 of 5) If screening tests and patient history suggest a TB infection, then the next steps include: – Determination of latent or active infection – X-ray or CT scan to assess lung damage Copyright © 2023 Pearson Education, Inc. All Rights Reserved Antibiotic Resistance (1 of 3) Multidrug-resistant strains (MDR TB strains) – Resistant to isoniazid and/or rifampin – Can be found in all countries ▪ Common in the Russian Federation, India, and China Extensively drug-resistant (XDR TB strains) – Resistant to first-line defense drugs – Rare Copyright © 2023 Pearson Education, Inc. All Rights Reserved Antibiotic Resistance (2 of 3) Active TB caused by an MDR or XDR TB strain is treated: – For up to two years – Requires expensive drugs – Drugs have more side effects and lower cure rates Copyright © 2023 Pearson Education, Inc. All Rights Reserved Antibiotic Resistance (3 of 3) World Health Organization estimates: – 206,000 cases of MDR TB worldwide in 2019 ▪ ~ 10% increase from 2018 – ~ 57% chance of curing MDR TB infections – ~ 39% chance of curing XDR TB infections Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Tuberculosis Causative agent Primarily Mycobacterium tuberculosis; acid-fast, Gram-positive bacterium Epidemiology Worldwide incidence, with Africa and Asia being the most affected; reservoir is humans and diseased animals; 4- to 8- week incubation period with 90–95% of infection events leading to latent TB; about 5% of these latent infections progress to active TB within 5 years; another 5% will progress to an active infection within the patient’s lifetime Transmission & Transmitted by respiratory droplets; highly communicable; prevented by the bacillus Calmette–Guérin (BCG) vaccine prevention Signs & symptoms Active TB is characterized by cough (sometimes with blood-tinged sputum), fever, night sweats, fatigue, and weight loss Pathogenesis & Specialized waxy cell wall makes these bacteria resistant to immune system defenses and protects the bacteria against virulence factors antibiotics; bacteria avoid destruction within macrophages and can escape the phagolysosome and grow within macrophages Diagnosis & Diagnostic tools include: the Mantoux tuberculin skin test; fluorescent microscopy or acid-fast staining to identify treatment mycobacteria in sputum smears; culture techniques; Xpert MTB/RIF test; and immune response evaluation using interferon gamma (IGRA). Latent TB is usually treated with isoniazid and/or rifampin for 3–9 months; active TB is often treated with a combination of four drugs: isoniazid, rifampin, pyrazinamide, and ethambutol (or streptomycin) for the first 2 months, followed by isoniazid and rifampin for the next 4–7 months; treatment for resistant strains is much longer and varied based on drug-resistance profiles of the bacterium. Sirturo (bedaquiline) may be used as a part of combination therapy to treat MDR and XDR TB Copyright © 2023 Pearson Education, Inc. All Rights Reserved Pneumonia is Among the Leading Causes of Death in the United States (1 of 6) Pneumonia – Inflammation of the lower respiratory tract, especially of the alveoli Etiological agent – >100 different microbes ▪ Certain bacteria, viruses, fungi, protists, or parasitic worms ▪ Bacteria and viruses cause most cases Copyright © 2023 Pearson Education, Inc. All Rights Reserved Pneumonia is Among the Leading Causes of Death in the United States (2 of 6) Characteristics – Leading cause of death from an infectious agent in the United States – Kills about a million children under age 5 every year worldwide Signs and symptoms – Fever – Cough – Dyspnea – Tachypnea Copyright © 2023 Pearson Education, Inc. All Rights Reserved Pneumonia is Among the Leading Causes of Death in the United States (3 of 6) Pneumonia is among the most common healthcare- acquired infections (HAIs) Three categories: – Healthcare-acquired pneumonia (HCAP) – Hospital-acquired pneumonia (HAP) – Ventilator-associated pneumonia (VAP) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Pneumonia is Among the Leading Causes of Death in the United States (4 of 6) Community-acquired pneumonia (CAP) – Pneumonia that has developed in a patient who was not recently hospitalized or admitted to some other healthcare facility – In the United States: ▪ ~ 1,000,000 per year are hospitalized due to pneumonia ▪ ~ 50,000 die from pneumonia Copyright © 2023 Pearson Education, Inc. All Rights Reserved Pneumonia is Among the Leading Causes of Death in the United States (5 of 6) Typical pneumonia – Illness resembling pneumococcal pneumonia (pneumonia caused by S. pneumoniae) – Characterized by signs and symptoms of consolidation Atypical pneumonia – Bacterial pneumonia that is not characterized by signs and symptoms of consolidation Copyright © 2023 Pearson Education, Inc. All Rights Reserved Pneumonia is Among the Leading Causes of Death in the United States (6 of 6) Table 16.2 Clinical Presentation of Pneumonia Clinical Feature Typical Pneumonia Atypical Pneumonia General Presentation High fever Fever usually lower Sudden onset of severe chills Little to no chills Shortness of breath Shortness of breath Cough with sputum (productive Cough with little or no sputum (nonproductive cough) cough) Usually no chest pain upon inhaling Chest pain when inhaling Runny nose, muscle aches, joint aches usually present Runny nose, muscle aches, joint Usually community acquired aches usually absent Onset is usually more subtle than for typical pneumonia Physical Examination Noticeable respiratory distress Limited respiratory distress Consolidation usually present (fluid Limited consolidation (minimal fluid in lungs) accumulation in the lungs) Auscultation (or listening to the patient’s breathing sounds with a stethoscope) reveals a crackling sound (or rales) as the patient breathes Chest X-ray Reveals fluid accumulation in the lung X-ray often looks worse than the patient appears or feels air sacs in one or both lungs May see white opaque areas in both lungs in a patchy or a (consolidation) diffuse pattern Usually an opaque white area is Atelectasis (collapse of the lung air sacs) may be evident visible in at least one lung lobe Usually only a small amount of fluid in the lung air sacs Consolidation (fluid in lungs) is not necessarily evident Sputum Culture Reveals Gram-positive or Gram-negative Often an agent is not successfully cultured from sputum bacteria Prevalence 4 out of 5 pneumonia cases 1 out of 5 pneumonia cases Copyright © 2023 Pearson Education, Inc. All Rights Reserved Clinical Vocabulary (6 of 7) Healthcare-acquired infection (HAI): an infection that a patient develops while receiving care for another condition in a healthcare setting Community-acquired infection (CAI): obtained from a human, animal, or environmental source in a non- healthcare setting Consolidation: refers to the apparent merging of the lung air sacs (alveoli) when fluid accumulates in the lungs; evident as white opaque areas by X-ray imaging Copyright © 2023 Pearson Education, Inc. All Rights Reserved Clinical Vocabulary (7 of 7) Bacteremia: presence of bacteria in the blood; usually confirmed by culturing bacteria from a blood sample Copyright © 2023 Pearson Education, Inc. All Rights Reserved Pneumococcal Pneumonia (1 of 3) Pneumococcal pneumonia Etiological agent – Streptococcus pneumoniae – Gram-positive, encapsulated diplococcus of the Group B streptococci (GBS) Prevention – Pneumococcal conjugate vaccines ▪ PCV-13 (Prevnar 13®) ▪ PPSV-23 (Pneumovax®) is recommended for people age 65 and older Copyright © 2023 Pearson Education, Inc. All Rights Reserved Pneumococcal Pneumonia (2 of 3) Characteristics – Most common form of bacterial pneumonia – Humans are the only known natural source of pneumococcal bacteria – People under age 5 and over age 65 are at the greatest risk – Symptoms usually come on quite suddenly Transmission – Respiratory droplets Copyright © 2023 Pearson Education, Inc. All Rights Reserved Pneumococcal Pneumonia (3 of 3) Mechanism of disease – Colonizes the nasopharynx of a new host – May spread to the middle ear and cause otitis media – May spread to the lungs and cause pneumonia Complications – May spread from the lungs to the bloodstream, leading to bacteremia – Meningitis Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Typical Pneumonia (1 of 2) Disease Pneumococcal pneumonia Haemophilus pneumonia Causative Streptococcus pneumoniae; Gram- Haemophilus influenzae; Gram-negative bacterium agent positive bacterium Epidemiology Worldwide; most common cause of Nontypable H. influenzae remains a leading cause of community-acquired pneumonia; community-acquired pneumonia in adults; 2- to 4-day people under age 5 and over age 65 incubation are at the greatest risk; 1- to 3-day incubation Transmission & Respiratory droplets; transmitted from Respiratory droplets; contact with discharge from the nose prevention person to person; prevented by PCV- and throat; commonly carried asymptomatically in the 13 (Prevnar 13 ®) and PPSV-23 nasopharynx; infections caused by typable H. influenzae (Pneumovax®) vaccines prevented by childhood Hib conjugate vaccine Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Typical Pneumonia (2 of 2) Signs & Symptoms are characterized by a sudden Infections causing pneumonia present symptoms high fever and episodes of shaking chills; fever (but older people may have lower cough, chest pain, shortness of breath, than normal body temperature), chills disorientation, and rust-colored, and sweating, cough, chest pain, and bloodtinged sputum are also sometimes shortness of breath; sometimes seen headache, muscle pain, and fatigue are present as well Pathogenesis Capsule protects against phagocytosis; Capsule protects against phagocytosis & virulence pneumolysin inhibits ciliary action of the and is used for adhesion to host factors mucociliary escalator; produces hydrogen tissues; endotoxin is present in the peroxide, which can cause oxidative bacterium’s outer membrane damage in host tissues Diagnosis & Diagnosed upon culturing bacterium from Diagnosis is confirmed by culture treatment patient samples; urine samples can also techniques or through detection of be used to detect the C-polysaccharide bacterial DNA or antigens; treatable antigen of Streptococcus pneumoniae; with many different antibiotics commonly treated with cephalosporins or (cephalosporins and quinolones are penicillin commonly prescribed) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Haemophilus influenzae (Hib) Pneumonia (1 of 2) Haemophilus influenzae (Hib) pneumonia Etiological agent – Haemophilus influenzae – Gram-negative bacteria – Typable strains based on analyses of polysaccharide capsules ▪ 6 major serotypes (a through f) – Nontypable strains ▪ Lack polysaccharide capsules Copyright © 2023 Pearson Education, Inc. All Rights Reserved Haemophilus influenzae (Hib) Pneumonia (2 of 2) Characteristics – Does not cause influenza – Can cause of epiglottitis, cellulitis, pneumonia, and meningitis – Hib is mainly a pathogen in children under age 6 – Nontypable strains are the leading cause of community-acquired pneumonia in adults Prevention – In the United States, five licensed vaccines have reduced occurrence to fewer than 50 cases per year Copyright © 2023 Pearson Education, Inc. All Rights Reserved There are Six Leading Causes of Atypical Bacterial Pneumonia (1 of 2) Leading causes of atypical bacterial pneumonia: – Zoonotic illness ▪ Q fever ▪ Psittacosis ▪ Tularemia – Non-zoonotic illness ▪ Chlamydia pneumoniae ▪ Mycoplasma pneumoniae ▪ Legionella species Copyright © 2023 Pearson Education, Inc. All Rights Reserved There are Six Leading Causes of Atypical Bacterial Pneumonia (2 of 2) C. pneumoniae and M. pneumoniae – Cause  80% of all atypical pneumonia cases – Cause up to 17% all pneumonia in adults and young children Copyright © 2023 Pearson Education, Inc. All Rights Reserved Mycoplasma Pneumonia (Walking Pneumonia) (1 of 2) Mycoplasma pneumonia (walking pneumonia) Etiological agent – Mycoplasma pneumoniae – One of the smallest self-replicating organisms – Lack a cell wall – Lives inside host cells Copyright © 2023 Pearson Education, Inc. All Rights Reserved Mycoplasma Pneumonia (Walking Pneumonia) (2 of 2) Characteristics – Most common cause of atypical community-acquired pneumonia – ~ 2 million cases in the United States every year – ~ 100,000 cases require hospitalization Signs and symptoms – Up to 20% of infections are asymptomatic – Symptomatic cases develop slowly – Mild pneumonia Copyright © 2023 Pearson Education, Inc. All Rights Reserved Chlamydophila Pneumonia (Formerly Chlamydia Pneumonia) (1 of 2) Chlamydophila pneumonia Etiological agent – Chlamydophila pneumoniae – Gram-negative bacteria – Lives inside host cells Characteristics – Common cause of sinusitis, pneumonia, bronchitis, and pharyngitis Copyright © 2023 Pearson Education, Inc. All Rights Reserved Chlamydophila Pneumonia (Formerly Chlamydia Pneumonia) (2 of 2) Signs and symptoms – Severity of the illness varies greatly – Starts with a sore throat – Progresses to a cough ▪ Lasts up to six weeks Complications – Causes 2–5 million cases of atypical pneumonia in the United States every year – ~ 500,000 cases require hospitalization Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Atypical Pneumonia, Part 1 (1 of 2) Disease Walking Pneumonia Chlamydophila Pneumonia Causative agent Mycoplasma pneumoniae (lack a cell wall) Chlamydophila pneumoniae; Gram- negative bacterium Epidemiology Common worldwide, but more cases in temperate Common worldwide; most cases occur climates; outbreaks are mostly in late summer; most in school-age children; about 10% of common in people ages 5 to 40 years; responsible community-acquired pneumonia and 5% for at least 40% of community-acquired pneumonia; of bronchitis; incubation period is about incubation period is 4–23 days 21 days Transmission & Respiratory droplets person to person; mainly Respiratory droplets person to person; prevention prevented by hand washing mainly prevented by hand washing Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Atypical Pneumonia, Part 1 (2 of 2) Signs & symptoms Usually include cold-like symptoms, a Symptoms vary widely but persistent dry cough, and mild fatigue typically start with a sore throat and then progress to a cough that lasts up to 6 weeks Pathogenesis & Specialized attachment structure that is Bacteria has mechanisms to virulence factors enriched with adhesins; induces thrive inside phagocytic cells damage to respiratory epithelium by and avoid destruction in hydrogen peroxide and superoxide phagolysosomes radicals Diagnosis & treatment Diagnosed using serology or nucleic Diagnosed by culture methods, acid-based tests; culturing the bacteria antigen detection, serology, and is challenging, but is sometimes used PCR; macrolides, for diagnosis; usually treated with fluoroquinolones, or tetracycline macrolides; not susceptible to penicillin- drugs are common therapies based drugs because these bacteria lack a cell wall Copyright © 2023 Pearson Education, Inc. All Rights Reserved Legionnaires’ Disease (Mainly Caused by Legionella Pneumophila) (1 of 2) Legionnaires’ disease Etiological agent – Legionella pneumophila – Gram-negative, motile coccobacilli Transmission – Aerosols Copyright © 2023 Pearson Education, Inc. All Rights Reserved Legionnaires’ Disease (Mainly Caused by Legionella Pneumophila) (2 of 2) Complications – Up to 18,000 people in the United States are hospitalized with Legionnaires’ disease – Up to 30% mortality rate in untreated cases L. pneumophila can cause two clinically distinct types of legionellosis: – Legionnaires’ disease – Pontiac fever Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Atypical Pneumonia, Part 2 (1 of 2) Disease Legionnaires’ Disease Pontiac Fever Causative agent Usually Legionella pneumophila; Gram-negative Usually Legionella pneumophila; Gram-negative bacterium bacterium Epidemiology Occurs worldwide year-round, but has higher incidence Found worldwide and occurs year-round; slightly from summer through early fall when air conditioners are in more prevalent in people under age 40; incubation high use; men and smokers are disproportionately affected; period of 1–3 days around 5,000 cases per year in the U.S.; incubation period of 2–14 days Transmission & Aerosols or aspiration of contaminated water; common in Aerosols or aspiration of contaminated water; prevention industrial air-conditioner systems and other artificial water common in industrial air-conditioner systems and systems; prevent by proper air-conditioning system other artificial water systems; prevent by proper air- cleaning and maintenance conditioning system cleaning and maintenance Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Atypical Pneumonia, Part 2 (2 of 2) Signs & symptoms Symptoms usually include high Symptoms include mild flu-like illness; fever, cough, and potentially only about 50% have a cough; vomiting severe atypical pneumonia and diarrhea have been described and, rarely, neurological symptoms are seen Pathogenesis & Bacteria have mechanisms to Pathogenesis is different from virulence factors thrive inside phagocytic cells and Legionnaires’ disease and is poorly avoid destruction in understood phagolysosomes Diagnosis & treatment Usually diagnosed using a urine Usually diagnosed using a urine antigen test for L. pneumophila antigen test for L. pneumophila serogroup 1; confirmed by culture serogroup 1; confirmed by culture methods; quinolones (example: methods; quinolones (example: ciprofloxacin) or macrolides ciprofloxacin) or macrolides (example: (example: erythromycin) are erythromycin) are common treatments common treatments Copyright © 2023 Pearson Education, Inc. All Rights Reserved Psittacosis or Ornithosis (Caused by Chlamydophila Psittaci) (1 of 2) Psittacosis Etiological agent – Chlamydophila psittaci – Gram-negative bacteria – Parasite of eukaryotic cells Characteristics – Most common among pet shop workers, zoo employees, taxidermists, veterinarians, poultry workers, and bird owners Copyright © 2023 Pearson Education, Inc. All Rights Reserved Psittacosis or Ornithosis (Caused by Chlamydophila Psittaci) (2 of 2) Transmission – Transmits from infected birds to humans – Inhalation of dust from dried bird droppings Signs and symptoms – Generalized muscle aches – Stiffness/spasms of back and neck muscles Complications in untreated cases – Recurring fever over several weeks – Fatal in 10–40% of cases Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Atypical Pneumonia, Part 3 (1 of 2) Disease Psittacosis or Ornithosis Q fever Tularemia Causative Chlamydophila psittaci; Coxiella burnetii; Gram- Francisella tularensis; agent Gram-negative bacterium negative bacterium Gram-negative bacterium Epidemiology Zoonotic disease; found Zoonotic disease; found Zoonotic disease; most worldwide, mainly in worldwide except in Antarctica prevalent in rural areas of North pigeons and psittacines; and New Zealand; most America, Europe, and northern most common among outbreaks linked to infected pets, Asia; host range includes people who contact birds; livestock, or wild animals; high- humans, birds, over 100 species incubation period of 5–14 risk groups include veterinarians, of wild animals (especially days meat packers, dairy workers, and rabbits), and occasionally livestock farmers; incubation domesticated animals; incubation period of 13–28 days period of 3–5 days Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Atypical Pneumonia, Part 3 (2 of 2) Transmission & Most commonly transmitted Transmitted by airborne bacteria from animal Transmitted by aerosolized Prevention via aerosols containing dust excrement and contaminated animal products; bacteria; not communicable; stirred up from infected bird amniotic fluid and placental tissue of infected prevented by an investigational droppings; not communicable; animals is a common exposure source for vaccine for people at high risk for prevented by limiting veterinarians; not communicable; prevented by exposure exposure to bird droppings the Q-vax vaccine for at-risk groups (not approved for use in U.S.) Signs & Fever that increases over Symptoms vary widely; include high fever, Symptoms include a sore throat, symptoms several days, chills, a severe nonproductive cough, muscle aches, chills, swelling of the lymph nodes, headache, and hacking sweats, weakness, nausea, vomiting, diarrhea, sudden fever, chills, muscle cough; often these are chest pain, severe headache, or abdominal pain aches, headache, joint pain, a dry accompanied by generalized cough, and progressive stiffness and back pain weakness with sudden onset Pathogenesis & Has mechanisms to thrive Can form a spore-like resistant structure in host Can escape phagosomes and virulence factors inside phagocytic cells and cells, allowing chronic infections; has live in macrophages; capsule is avoid destruction in mechanisms to thrive inside phagocytic cells and important for aerosolized forms; phagolysosomes avoid destruction in phagolysosomes siderophores bind and collect iron; pili can attach to host tissues Diagnosis & Diagnosed by serology and P Mainly diagnosed by patient history and Patient history of tick or deer fly treatment CR of respiratory samples; signs/symptoms; treated with doxycycline bites, or contact with sick or dead antibiotic of choice is animals; serology, PCR, and doxycycline culture methods can confirm diagnosis; treated with aminoglycosides Copyright © 2023 Pearson Education, Inc. All Rights Reserved Q Fever (Caused by Coxiella Burnetti) (1 of 2) Q fever (Query fever) Etiological agent – Coxiella burnetii – Gram-negative bacteria – Highly infectious—dose of one bacterial cell Signs and symptoms – Flu-like illness that can be accompanied by pneumonia Copyright © 2023 Pearson Education, Inc. All Rights Reserved Q Fever (Caused by Coxiella Burnetti) (2 of 2) Transmission – Livestock (e.g., cattle, sheep) become infected from ticks – People can become infected by: ▪ Inhaling dust or aerosols from feces, urine, or birth products ▪ Eating unpasteurized milk products Copyright © 2023 Pearson Education, Inc. All Rights Reserved Tularemia (Caused by Francisella Tularensis) (1 of 2) Tularemia Etiological agent – Francisella tularensis – Gram-negative bacteria – First isolated from ground squirrels – Can exist as a free-living bacterium or parasite of eukaryotic cells (e.g., macrophages) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Tularemia (Caused by Francisella Tularensis) (2 of 2) Characteristics – Remains infectious for long periods of time outside the host Transmission – Extremely infectious zoonotic disease – Inhalation of infectious aerosols ▪ Airborne when dried grasses or hay contaminated with infected animal carcasses are stirred up ▪ Skinning or butchering affected animals Copyright © 2023 Pearson Education, Inc. All Rights Reserved Fungal Respiratory System Infections After reading this section, you should be able to: Describe what a mycosis is and why they are becoming more common. State why certain mycoses are called endemic and others are not. Provide examples of three endemic mycoses and their clinical features. Describe the causative agents and clinical features of aspergillosis, mucormycosis, and Pneumocystis pneumonia. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Fungal Respiratory System Infections (1 of 2) Relative to bacterial and viral infections of the respiratory tract, mycoses are rare However, fungal infections are becoming more common due to: – Increased urban development and deforestation – Climate change – Increased number of people with weakened immunity Copyright © 2023 Pearson Education, Inc. All Rights Reserved Fungal Respiratory System Infections (2 of 2) Endemic fungi – Only grow in specific geographical locations – Cause endemic mycoses – Endemic mycoses caused by fungi that are considered true pathogens Ubiquitous fungi – Grow in varied climates and under diverse conditions – Some are part of the normal flora Respiratory mycoses contracted when fungal spores are inhaled Copyright © 2023 Pearson Education, Inc. All Rights Reserved Blastomycosis (Chicago Disease) (1 of 3) Blastomycosis (Chicago Disease) Etiological agent – Blastomyces dermatitidis – Dimorphic endemic fungus ▪ Parts of the United States – Mississippi and Ohio River valleys – Great Lakes region ▪ Parts of Canada – Great Lakes and St. Lawrence Seaway Copyright © 2023 Pearson Education, Inc. All Rights Reserved Blastomycosis (Chicago Disease) (2 of 3) Transmission – Noncommunicable – Saprophyte that thrives on decomposing plant matter in moist soil – Produces conidia spores – Become airborne – Inhaled when soil is disturbed by digging, wood clearing, or construction Copyright © 2023 Pearson Education, Inc. All Rights Reserved Blastomycosis (Chicago Disease) (3 of 3) Progression – Inside the lungs, spores germinate into unicellular, yeast-like form Complications – High mortality rates in immune-compromised due to disseminated blastomycosis Treatment – Antifungal drugs (e.g., amphotericin B, fluconazole, itraconazole, ketoconazole) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Blastomycosis (Chicago Disease) Causative agent Blastomyces dermatitidis or Paracoccidioides brasiliensis Epidemiology B. dermatitidis is mostly found in North America, whereas P. brasiliensis causes most cases in Latin America. Isolated incidence worldwide. There are approximately 1–2 symptomatic cases per 100,000 in endemic areas. Disease is most common in immune-compromised people. Incubation period is 3 weeks to 3 months. Transmission & B. dermatitidis transmits via conidia spores that are inhaled. Avoiding exposure is the best preventive method. prevention Signs & Flu-like with a fever, headache, cough, muscle aches, chills, and joint pain; pneumonialike symptoms are also common. symptoms Rarely, the fungus spreads throughout the body, causing disseminated blastomycosis, which has a poor prognosis. Pathogenesis & Paracoccidioides brasiliensis has adhesins to bind to human cells and can form a biofilm. It is also capable of inducing virulence factors apoptosis and host coagulation. Blastomyces dermatitidis also has adhesins and can deactivate some of the functions of macrophages in the lungs. Both of these fungi change into the parasitic yeast form upon exposure to human body temperature. Diagnosis & Common methods include chest X-rays, microscopic examination of sputum samples, and culture methods. treatment Immunoassays are also available. Treatments include antifungal drugs such as fluconazole, itraconazole, ketoconazole, or amphotericin B. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Coccidioidomycosis (Valley Fever) (1 of 3) Coccidioidomycosis (Valley Fever) Etiological agent – Coccidioides immitis ▪ Native to San Joaquin Valley, California – Coccidioides posadasii ▪ Mainly found in southwestern United States, northern Mexico, and parts of Central and South America Copyright © 2023 Pearson Education, Inc. All Rights Reserved Coccidioidomycosis (Valley Fever) (2 of 3) Transmission – Noncommunicable – Produce arthroconidia spores – Spread with the wind – Spores are inhaled Copyright © 2023 Pearson Education, Inc. All Rights Reserved Coccidioidomycosis (Valley Fever) (3 of 3) Mechanism of disease – In the lungs, the arthroconidia change – Develop into spherules – Spherules rupture release fungal endospores Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Coccidioidomycosis (Valley Fever) Causative agent Coccidioides immitis and Coccidioides posadasii Epidemiology The fungi are usually found in semi-arid or arid soil in the southwest and California, as well as northern Mexico. Although around 150,000 people are infected each year, 65% of cases are asymptomatic. In the U.S., 50–100 people per year die from it. Incubation period is 1–4 weeks. Transmission & prevention Transmits via inhalation of fungal spores. No preventive measures, beyond avoiding inhalation. Signs & symptoms Body aches, fever, cough, headache, knee and ankle joint pain, and a rash on the torso and extremities. If the fungus causes a disseminated infection, skin lesions and meningitis also commonly occur. Pathogenesis & virulence A protein found on the outer wall of spherules helps the fungus hide from the immune system. C. immitis can factors also prevent macrophages from producing nitric oxide that kills invading cells. Diagnosis & treatment Most cases are diagnosed using an immunoassay to find related antibodies. Chest X-rays and tissue biopsies are common. Treatment involves 6 months of antifungal drugs such as fluconazole, itraconazole, ketoconazole, or amphotericin B in severe cases. Prevention None, beyond avoiding exposure. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Histoplasmosis (1 of 4) Histoplasmosis Etiological agent – Histoplasma capsulatum – Dimorphic fungus – Found worldwide – Concentrated near river valleys ▪ In the United States.: Mississippi and Ohio River valleys Copyright © 2023 Pearson Education, Inc. All Rights Reserved Histoplasmosis (2 of 4) Transmission – Produces macroconidia and microconidia spores – Spores become airborne with dust or soil – Spores are inhaled – Spores germinate into the pathogenic, yeast-like form – Exposure to the fungus is largely occupational (e.g., poultry farmers, guano harvesters) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Histoplasmosis (3 of 4) Copyright © 2023 Pearson Education, Inc. All Rights Reserved Histoplasmosis (4 of 4) Characteristics – Grows mainly in soil enriched with bat and bird droppings Signs and symptoms – Only  5% of infections are symptomatic Complications – Immune-compromised patients are more likely to develop the disseminated form Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Histoplasmosis Causative agent Histoplasma capsulatum Epidemiology Much more common among populations with occupations that come into contact with bat or bird droppings. Where endemic, many people are exposed, but only around 5% are symptomatic. Immune-compromised patients are at greater risk. In Latin America, almost 30% of HIV patients coinfected with histoplasmosis die of the disease. Incubation period is 3–17 days. Transmission & Transmits via inhaled spores. To prevent, avoid caves, or wear masks in areas known to harbor the fungus, prevention including caves and chicken coops. Signs & symptoms Resembles atypical pneumonia (fever, chest pain, and dry, nonproductive cough). Fatigue and headache sometimes present. H. capsulatum can become disseminated into other parts of the body, with central nervous system infections being most severe. Pathogenesis & Some of its cell wall polysaccharides can resist macrophage binding. Even when ingested by the macrophage, it virulence factors can survive and scavenge iron from the cell. Diagnosis & treatment Detecting via immunoassays from a blood sample or urine is routine. Chest X-rays, microscopic examination of sputum or tissue, and culture methods are also used. The most common treatment is the antifungal itraconazole. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Ubiquitous Fungi Can Cause Serious Infections in Immune-Compromised Patients Endemic fungi can often establish infections in healthy people Ubiquitous fungi infections tend to occur only in immune- compromised people Copyright © 2023 Pearson Education, Inc. All Rights Reserved Aspergillosis (1 of 2) Invasive aspergillosis Etiological agent – Aspergillus species (e.g., A. fumigatus) Characteristics – Common soil fungus – Found throughout the world – 5 forms of invasive aspergillosis ▪ Pulmonary and rhinocerebral forms are the most common Copyright © 2023 Pearson Education, Inc. All Rights Reserved Aspergillosis (2 of 2) Transmission – Inhalation of spores – Almost exclusively seen in immune-compromised patients Complications – High mortality rate without early treatment Diagnosis – Cultured from a patient specimen – Microscopic observation in the sample Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Aspergillosis Causative agent Several species associated with invasive disease, but A. fumigatus is most common. Epidemiology Invasive aspergillosis is almost exclusively seen in immune-compromised patients, especially people undergoing cancer chemotherapy, those on high doses of corticosteroids, and those taking antirejection drugs after organ transplants. Incubation period is 2 days to 3 months. Transmission & Transmits by inhalation of spores. There is no vaccine, and the only prevention is to avoid inhaling the spores. prevention Signs & symptoms Fever, coughing up mucous plugs and possibly blood, and difficulty breathing. Pathogenesis & RodA proteins and DNH-melanin on the surface of A. fumigatus help it avoid immune detection prior to changing to virulence factors the yeast form. After the yeast form is engulfed by macrophages, it can prevent acidic digestion inside the phagolysosome. Infected cells are also prevented from undergoing apoptosis. Diagnosis & Diagnosis is made by a positive skin test that detects immune reaction to A. fumigatus, serological tests to detect treatment antibodies to A. fumigatus, or positive culture from sputum or tissue biopsy. Treatment starts immediately upon positive results, but the diagnosis is usually confirmed via culture from sputum. Intravenous voriconazole is the first- line treatment, sometimes in combination with other agents such as caspofungin, amphotericin B, and echinocandins. Itraconazole can also be used if first-line treatment fails. Mortality rate is 30–90% in symptomatic cases. Copyright © 2023 Pearson Education, Inc. All Rights Reserved Mucormycosis (1 of 2) Mucormycosis Etiological agent – Rhizopus arrhizus Characteristics – Found in soil enriched with rotting wood – Rare disease ▪ 2 cases per million people in the United States Copyright © 2023 Pearson Education, Inc. All Rights Reserved Mucormycosis (2 of 2) Transmission – Inhalation of spores Progression – Varies depending on patient factors and time of detection Copyright © 2023 Pearson Education, Inc. All Rights Reserved Disease Snapshot: Mucormycosis Causative agent Most commonly Rhizopus arrhizus Epidemiology In the U.S., fewer than 2 people per million in the population develop this illness. However, in some countries, cases rose 70% in the past decade. The fungus is usually found in rotting wood, and human exposure is common. Infection is usually confined to immune-compromised patients. If the infection is detected late in immune-compromised patients, mortality can be as high as 50%. Incubation is 3–10 days. Transmission & prevention Transmits through respiratory route via inhaled fungal spores. No preventive vaccine or methods, beyond avoidi