Pharyngitis Causative Agents M ost often caused by the common cold viruses (adenovirus, rhinovirus, influenza, coronavirus, and respiratory syncytial virus), but occasionally by Epstein-Barr virus, herpes simplex virus, cytomegalovirus, or HIV. Could be a r esult of mechanical irritation from prolonged shouting or drainage from the sinus cavity Most serious cases of pharyngitis caused by Streptococcus pyogenes , a group A beta-hemolytic streptococcus. M ost commonly between ages 5 and 15 3
Pharyngitis: Streptococcus pyogenes Gram-positive coccus that grows in chains Does not form endospores Nonmotile Forms capsules and slime layers Facultative anaerobe that ferments a variety of sugars Does not produce catalase : Peroxidase system allows for its survival in the presence of oxygen 4
Pharyngitis: Streptococcus pyogenes Pathogenesis Untreated streptococcal throat infections can result in serious complications Scarlet fever : a predominantly childhood disease, a result of an infection of S. pyogenes that produce an erythrogenic toxin , leading to a diffuse pink-red cutaneous flush that blanches with pressure. S. pyogenes infected with a bacteriophage: Produces erythrogenic toxin Sandpaper-like rash with high fever : the rash is mainly on the abdomen or lateral chest and as dark red lines in skinfolds ( Pastia lines ) or as circumoral pallor. The rash consists of characteristic numerous small (1- to 2-mm) papular elevations , giving a sandpaper quality to the skin. The upper layer of the previously reddened skin often desquamates after fever subsides. The rash usually lasts 2 to 5 days. Transmission enhanced in close contact environment . (day care or school) Fatality rate up to 95% before the antibiotics, Since the advent of antibiotic therapy, the mortality rate of treated scarlet fever is < 1% . 5
Pharyngitis: Streptococcus pyogenes Pathogenesis Scarlet Fever 6 The classic scarlet fever rash initially appears as tiny red papules on the chest and abdomen. Papules may then spread over the body. The rash resembles sunburn, feels like rough sandpaper, and lasts about 2 to 5 days.
Pharyngitis: Streptococcus pyogenes Pathogenesis Rheumatic fever Rheumatic fever : an inflammatory disorder , occurs in < 3% of patients in the weeks after untreated GABHS pharyngitis . It is due to an immunologic cross-reaction between streptococcal M proteins and the heart muscle D iagnosis of a first episode is based on a combination of arthritis, carditis, chorea, specific cutaneous manifestations, and laboratory test results One of the most important reasons for treating GABHS pharyngitis (strep throat) is to prevent rheumatic fever. 7
Pharyngitis: Streptococcus pyogenes Virulence Factors Virulence is a result of two phenomena: Ability of surface antigens to mimic host proteins Possession of superantigens ( a class of antigens that result in excessive activation of the immune system. ) Other factors include: Specialized polysaccharides protect the bacterium from being dissolved by lysozyme Lipoteichoic acid : contributes to the adherence of the cell wall to the epithelial cells of the pharynx M protein : resists phagocytosis, contributes to adherence Hyaluronic acid capsule: contributes to adhesiveness 8
Group A Streptococcus Access the text alternative for slide images. 9
Pharyngitis: Streptococcus pyogenes Extracellular Toxins Streptolysins : O and S T wo hemolytic exotoxins from Streptococcus pyogenes. Types include streptolysin O, which is oxygen-labile, and streptolysin S, which is oxygen-stable. Cause beta-hemolysis of sheep blood agar. Lysis of the cell membrane of RBC, polymorphonuclear leukocytes, platelets, and subcelullar organelles Rapidly injure cells and tissues Erythrogenic toxin : Known to damage the plasma membrane of blood capillaries under the skin, which makes it responsible for the bright red rash Induces fever Only lysogenic strains of S. pyogenes that contain genes from a temperate bacteriophage can synthesize this toxin . ( The infection of Streptococcus pyogenes T25(3) with the temperate bacteriophage T12 results in the conversion of the nontoxigenic strain to type A streptococcal exotoxin (erythrogenic toxin) production.) 10
Pharyngitis: Streptococcus pyogenes Transmission and Epidemiology 30% of sore throats may be caused by S. pyogenes Transmission via respiratory droplets or direct contact with mucus secretions Humans are the only significant reservoir Each year, the bacterium affects 700 million people globally, leading to 160,000 deaths. More than 80 serotypes of S. pyogenes exist; immunity is serotype specific 11
Pharyngitis: Streptococcus pyogenes Prevention and Treatment Prevention : No vaccine exists Prevention through good hand washing, especially after coughing, sneezing, and before preparing foods and eating Treatment: Penicillin is the antibiotic of choice. Cephalexin used for patients with penicillin allergy Most sore throats caused by S. pyogenes can resolve on their own, but antibiotic treatment is needed to prevent serious sequelae 13
The Common Cold Causative agent: over 200 different viruses: Rhinoviruses: 150 serotypes Coronavirus Adenovirus Respiratory syncytial virus Transmission: Indirect contact, droplet contact Symptoms: Sneezing Scratchy throat Runny nose Fever in children 14
The Common Cold , Facts About 50% of all colds are caused by one of the > 100 serotypes of rhinoviruses. Rhinovirus infections are most common during fall and spring and are less common during winter. The most potent deterrent to infection is the presence of specific neutralizing antibodies in the serum and secretions, induced by previous exposure to the same or a closely related virus. Susceptibility to colds is not affected by exposure to cold temperature, host health and nutrition, or upper respiratory tract abnormalities ( eg , enlarged tonsils or adenoids) Coronaviruses cause some outbreaks 15
The Common Cold I ncubation period of 24 to 72 hours, C old symptoms begin with a scratchy or sore throat, followed by sneezing, rhinorrhea, nasal obstruction, and malaise. T T emperature is usually normal, particularly when the pathogen is a rhinovirus or coronavirus. Nasal secretions are watery and profuse during the first days but then become more mucoid and purulent. Mucopurulent secretions do not indicate a bacterial superinfection. Cough is usually mild but often lasts into the 2nd week. Most symptoms due to uncomplicated colds resolve within 10 days. 16
Acute Otitis Media (Ear Infection) Viral infections of the upper respiratory tract lead to inflammation of eustachian tubes, buildup of fluid in the middle ear , and bacterial multiplication in the fluid Causative agents: Streptococcus pneumoniae Candida auris Other bacteria/viruses Prevention : Prevnar Treatment: “Watchful waiting” Antibiotics Tympanic membrane tubes 17
Infected Middle Ear 18
Highlight Disease: Pneumonia Pneumonia is an acute inflammation of the lung , in which fluid fills the alveoli Initial diagnosis is usually based on chest x-ray and clinical findings. Bacteria, fungi, and a wide variety of viruses can cause pneumonias Pneumonia can be deadly, and across the globe, more children under the age of 5 die from pneumonia than any other infectious disease 19 Lower respiratory tract
Pneumonia Disease characterized by an anatomical diagnosis ( bronchopneumonia or lobar pneumonia ) : In general, pneumonia is an Inflammatory condition of the lungs in which fluid fills the alveoli A wide variety of microorganisms can cause pneumonia: Have appropriate characteristics that allow them to penetrate and survive in the lower respiratory tract Avoid phagocytosis or avoid being killed once inside macrophage More children die of pneumonia than any other infectious disease 20
Pneumonia Causes, symptoms, treatment, preventive measures, and prognosis of pneumonia differ depending on: whether the infection is bacterial, mycobacterial, viral, fungal, or parasitic; whether it is acquired in the community or hospital; whether it occurs in a patient treated with mechanical ventilation; and whether it develops in a patient who is immunocompetent or immunocompromised. 21
Community-Acquired Pneumonia Streptococcus pneumoniae : Factors that favor the ability of the pneumococcus to cause disease are old age, the season underlying viral respiratory disease, diabetes, and chronic abuse of alcohol or narcotics Legionella : Less common, serious cause of disease Mycoplasma pneumoniae and Chlamydophila pneumoniae : Walking pneumonia Histoplasma capsulatum : fungus that infects many people but causes a pneumonia-like disease in relatively few Hantavirus Pneumonia can be a secondary effect of influenza 22
Signs and Symptoms: SARS-CoV-2 COVID-19 may cause no symptoms at all, or it may lead to death quickly It was first recognized for its pneumonia manifestations, it can damage blood vessels all over the body, leading to damage to the heart, kidneys, brain, and other organs Patients who have been hospitalized as well as those with milder symptoms report post-COVID symptoms that reflect the systemic nature of this virus, lasting for weeks to months Children and young adults also are at risk for a condition called MIS-C (multi-system inflammatory syndrome in children) 24
Causative Agent: SARS-CoV-2 SARS-CoV-2 is a coronavirus It is an RNA virus with spikes (glycoproteins) which allow it to attach to host cells These spikes are visible under the electron microscope and give it its name corona, for crown The binding of a receptor expressed by host cells is the first step of viral infection followed by fusion with the cell membrane of lung epithelial cells. 25
Pathogenesis: SARS-CoV-2 Is highly pathogenic when initially crossing to humans It was first identified as a pneumonia-causing virus, it also has systemic effects It triggers widespread activation of bradykinins , which cause damage to lungs and other tissues, including cardiac injuries. Significantly high blood levels of cytokines and chemokines were noted in patients with COVID-19 infection Early studies suggest that the virus has proteins that block the production of interferon, crippling an important part of the innate immune response 26
Pathogenesis: SARS-CoV-2 27
Transmission and Epidemiology: SARS-CoV-2 SARS-CoV-2 is transmitted through droplet and airborne contact spread by coughing or sneezing. Other routes of transmission are not yet well established. N o evidence that there is transmission from mother to child. One factor making the pandemic difficult to control is that it is transmissible even in the absence of symptoms, so “well” people circulating between public spaces and home are reservoirs and carriers . 28
SARS-CoV-2 (2) Culture and Diagnosis Scientists acted quickly and learned to grow the virus in cell culture, Testing for the virus was not terribly successful in the beginning Real-time reverse transcriptase–polymerase chain reaction (RT-PCR) Antigen testing of upper respiratory secretions Prevention and Treatment Vaccine development started immediately but will take time to test and deploy The best preventions in lieu of a vaccine are physical distancing and the use of face masks. Supportive care Sometimes, for mild to moderate illness with high-risk of severe disease: nirmatrelvir /ritonavir combination; remdesivir (short course); molnupiravir For severe illness: remdesivir ; dexamethasone ; immunomodulators 29
Community-Acquired Pneumonia: Streptococcus pneumoniae Pneumococcus Small, gram-positive flattened coccus , encapsulated , often appearing in pairs lined up end to end. T he pneumococcus capsule consists of a complex polysaccharide that determines serologic type and contributes to virulence and pathogenicity. Currently, > 90 different pneumococcal serotypes. C apsule is critical for evading phagocytosis . Factors that favor the ability of the bacterium to cause disease: Old age The season Underlying viral respiratory disease Diabetes Sickle cell disease or other hemoglobinopathies Chronic abuse of alcohol or narcotics Vaccination with PPSV23 or PCV13 encouraged in older adults 30
Community-Acquired Pneumonia: Legionella pneumophila Weakly gram-negative bacterium that ranges from coccus to filaments Able to survive and persist in natural habitats. Widely distributed in tap water, cooling towers, spas, ponds, and other fresh water . The infection is usually acquired by inhaling aerosols (or less often aspiration) of contaminated water ( eg , as generated by shower heads, misters, decorative fountains, whirlpool baths, or water-cooling towers for air-conditioning). Legionella infection is not transmitted from person to person Resistant to chlorine. Can live in association with free-living amoebas Released during aerosol formation and carried long distances Legionella infection is more frequent and more severe in the following: Older people. Patients with diabetes or chronic obstructive pulmonary disease (COPD). Cigarette smokers. Immunocompromised patients (typically with diminished cell-mediated immunity) 31
Community-Acquired Pneumonia: Atypical Pneumonias Symptoms do not resemble those of pneumococcal or other severe pneumonias Mycoplasma and Chlamydophila : Transmitted by aerosol droplets among people in confined to close living quarters Family, students, the military “Walking pneumonia”: Lack of acute illness in most patients 32
Community-Acquired Pneumonia: Atypical Pneumonias Community-acquired pneumonia is defined as pneumonia that is acquired outside the hospital . The infection is caused by different bacteria than the more common microbes that can cause pneumonia. Milder symptoms diagnosis is : nucleic acid–based testing or detection of antibodies. Culture is technically difficult. Treatment: Macrolides are usually the antimicrobials of choice. Most species are also sensitive to fluoroquinolones and tetracyclines. 33
Community-Acquired Pneumonia(CAP): Respiratory Viruses Very common causes of community-acquired pneumonia Respiratory viruses, particularly influenza and RSV , are a common cause of CAP . This includes influenza, parainfluenza virus, human coronaviruses ( HCoV ) HKU1 and NL-63, and human bocavirus Either residents of the upper respiratory tract or acquired through daily activities Viral pneumonias are generally mild 34
Healthcare-Associated Pneumonia Hospital-acquired pneumonia (HAP) develops at least 48 hours after hospital admission Up to 1% of hospitalized or institutionalized people experience pneumonia The most common pathogens are gram-negative bacilli and Staphylococcus aureus ; antibiotic-resistant organisms are an important concern It is most associated with mechanical ventilation , via an endotracheal or tracheostomy tube: This is sometimes labeled “ventilator-associated pneumonia,” or VAP Mortality rate: 30 to 50%. Overall prognosis is poor, due in part to comorbidities . 35
Healthcare-Associated Pneumonia Causes, Culture and Diagnosis Most frequent causes: MRSA strains of Staphylococcus aureus Gram-negative bacteria : Klebsiella pneumoniae, Enterobacter, E. coli, Pseudomonas aeruginosa, and Acinetobacter Many are polymicrobial in origin Sputum and tracheal swabs are not useful Endotracheal tube or bronchoalveolar lavage cultures provide better information but are invasive Antibiotics the patient is already receiving may affect results 36
Healthcare-Associated Pneumonia Prevention and Treatment The most common cause of hospital-acquired pneumonia is microaspiration of bacteria that colonize the oropharynx and upper airways, Elevation of patients’ heads to a 30- to 45-degree angle helps reduce aspiration of secretions Good preoperative education of patients about the importance of deep breathing; and frequent coughing can reduce postoperative infection rates Proper care of mechanical ventilators and respiratory therapy equipment Empiric therapy should begin as soon as hospital-associated pneumonia is suspected 37
Highlight Disease: Influenza Cyclical increase of influenza during the winter months: Some strains may cause worldwide pandemics Evolution of the influenza virus is illustrative of how other viruses cause serious diseases Signs and symptoms: Begin in upper respiratory tract Can progress to lower tract Headache, chills, dry cough, body aches, fever, stuffy nose, and sore throat Extreme fatigue Secondary infections Occasionally leads to pneumonia 38
Influenza Causative Agent Influenza A, B, and C viruses in the family Orthomyxoviridae : Spherical particles 80 to 120 nanometers in diameter Lipoprotein envelope studded with glycoprotein spikes: Hemagglutinin (H) Neuraminidase (N) Ion channels ssRNA genome known for its extreme variability 10 genes on 8 separate RNA strands Access the text alternative for slide images. 39
Influenza Antigenic drift : Mutation of glycoproteins (H, N) Antigens gradually change their amino acid composition, resulting in decreased ability of host memory cells to recognize them Antigenic drift is the reason that a new vaccine is required for each year: This vaccine is called the seasonal vaccine Antigenic shift : RNA exchange between different influenza viruses Occurs during coinfection of a host cell More likely to produce pandemic strains 40
Influenza Pathogenesis and Virulence Factors Virus binds to ciliated cells of the respiratory mucosa Infection causes the rapid shedding of these cells along with a load of viruses Severe inflammation, irritation in lungs due to “cytokine storm” Glycoproteins and their structure are important virulence determinants: Mediate adhesion of the virus to host cells Change to evade immune recognition 42
Influenza Transmission and Epidemiology Inhalation of virus-laden aerosols and droplets Indirect contact with fomites Transmission aided by crowding, poor ventilation Drier air of winter facilitates spread of the virus Approximately 12,00 to 60,000 influenza deaths annually Mainly affects the very young and the very old 43
Influenza Culture and Diagnosis Culture and non-culture-based tests to diagnose infection RT-PCR is preferred method In 2009, officials did not often test for H1N1 but tested for influenza A or B virus, assuming if it was A then it was H1N1 because the circulating seasonal virus was influenza B When specimens were tested, 100% of the influenza A isolates were in fact the H1N1 44
Influenza Prevention Vaccination : Several types of influenza vaccines: Vaccines can be administered intramuscularly (injected) or intradermally, via nasal spray Some of the vaccines consist of inactivated (killed) viruses; others contain live attenuated virus CDC recommends those over the age of 65 are urged to get the high-dose vaccine to improve their immunity to the virus New vaccine prospects: Target ion-channel proteins to eliminate all strains ; would not need to be given every year 45
Respiratory Syncytial Virus Causative agent: Respiratory syncytial virus ( RSV ) Transmission: Droplet and indirect contact via fomite Peak incidence in the winter and early spring Premature babies and children 6 months or younger are susceptible 100,000 children hospitalized each year in the U.S. Virulence factor: Syncytia formation Prevention: Passive antibody for high-risk children 46
Tuberculosis 1 Tuberculosis is an ancient human disease: Called “Captain of the Men of Death” and “White Plague” Since the mid-1980s has reemerged as a serious threat 1.7 billion currently infected worldwide Signs and symptoms: Humans easily infected but quite resistant to disease development 85% TB cases contained in the lungs Clinical tuberculosis forms: Primary Secondary (reactivation or reinfection) Disseminated/extrapulmonary 47
Extrapulmonary Tuberculosis Infection outside of the lungs: Regional lymph nodes Kidneys (renal tuberculosis) Long bones Genital tract (genital tuberculosis) Brain and meninges (tubercular meningitis) Immunosuppressed patients, young children These complications are often fatal 49
Secondary (Reactivation) Tuberculosis 1 Live bacteria can remain dormant, then reactivate Chronic tuberculosis : tubercles expand causing cavities in the lungs, and drain into the bronchial tubes and upper respiratory tract Severe symptoms develop, including : Violent coughing with greenish or bloody sputum Low-grade fever Anorexia, weight loss Extreme fatigue, night sweats Chest pain Untreated secondary disease has a 60% mortality rate 50
Tuberculosis 2 Causative agents: Mycobacterium tuberculosis : Acid-fast bacillus, strict aerobe, slow-growing Mycolic acids, waxes in cell walls Resistant to drying and disinfectants Cord factor linked to virulence Mycobacterium avium infection in AIDS patients Pathogenesis and virulence factors: Waxy cell wall enhances survival in environment and within macrophages Stimulates strong cell-mediated immune response, enhancing disease pathology 51
Tuberculosis Transmission and Epidemiology T ransmitted via droplets of respiratory mucus suspended in air Can survive for 8 months in fine aerosol particles Susceptibility influenced by: Inadequate nutrition Debilitation of the immune system Poor access to medical care Lung damage Genetics Some populations are at higher risk of infection or of developing life-threatening forms of the disease 60% of U.S. cases are among foreign-born persons People who work in nursing homes, hospitals, or jails are at higher risk 52
Tuberculosis Prevention Limiting exposure to infectious airborne particles Patient isolation in negative-pressure rooms when a person with active TB is identified Live attenuated vaccine (BCG) : Not used in U.S. Bovine tuberculosis bacterium Vaccinated individuals will respond positively to tuberculin test 54
Tuberculosis Treatment Treatment of latent TB: Rifampin and rifapentine : 4 and 3 months, respectively Isoniazid: 9 months Treatment of active TB: Rifampin, isoniazid, ethambutol, and pyrazinamide : 2 months Rifampin and isoniazid : either 4 or 7 months, depending on the case One of the biggest problems with TB therapy is noncompliance Failure to adhere to the antibiotic regimen results in MDR-TB 55
Multidrug-Resistant Tuberculosis (MDR-TB) Defined as being resistant to at least isoniazid and rifampin : Requires treatment of 18 to 24 months with four to six drugs Common in people who have been previously treated for tuberculosis: Approximately 500,000 new cases of MDR-TB were diagnosed in 2015 45% were in India, China, and the Russian Federation People with MDR-TB are sicker and have higher mortality rates than those infected with non-MDR-TB : Even with treatment, about half of these patients die 56
Extensively Drug-Resistant Tuberculosis (XDR-TB) MDR-TB strains with resistance to two additional drugs: Reported in 117 countries 9% of MDR-TB cases worldwide Few treatment options Estimated 70% mortality rate within months of diagnosis 57