Upper Respiratory Tract Infections
Return to Syllabus  

INFECTIONS OF THE UPPER RESPIRATORY TRACT


General Goal: To know the major cause(s) of these diseases, how they are transmitted, and the major manifestations of each disease.

Specific Educational Objectives: The student should be able to:

1. recite the common cause(s) of these disease.

2. describe the common means of transmission.

3. describe the major manifestations of this infection.

4. describe how you diagnose, treat and prevent this infection.

Reading: DL Kasper and AS Fauci, 2013. Harrison's Infectious Diseases, Chapter 17. 2nd Edition. Pg. 192-206 McGraw Hill Education, New York

Lecture: Dr. Neal R. Chamberlain

References: 

Cherry, CK, CW. Burt, and DA. Woodwell. National Ambulatory Care Survey, 1999. Advance data from vital and health statistics of the national center for health statistics, No. 322.  July 17, 2001. U.S. department of Health and Human Services, http://www.cdc.gov/nchs/data/ad/ad322.pdf

Bisno, AL. et. al. Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. 2002. Clinical Infectious Diseases. 35:113-25.

Bisno, AL, GS. Peter, and EL. Kaplan. Diagnosis of strep throat in adults: are clinical criteria really good enough? 2002. Clinical Infectious Diseases. 35:126-29.

National Guideline Clearinghouse. University of Michigan Health System. Acute Pharyngitis. http://www.guidelines.gov/body_home_nf.asp?view=home

Huffman, GB. Diagnosing Strep Throat: Are There Reliable Clues? American Family Physician. July 1, 2001. http://www.aafp.org/afp/20010701/tips/2.html 


III. Pharyngitis

Pharyngitis (sore throat) is a common disease resulting in over 15 million physician office visits each year in the US. Most cases of pharyngitis are caused by viruses.

 

Etiology

Pharyngitis can be caused by many different microorganisms; however, 90% of sore throats in adults and 60–75% of sore throats in children are caused by viruses (Table URI-5). S pyogenes (b-hemolytic group A Streptococcus) is the most common bacterial cause of acute pharyngitis.

 

Table URI-5. Some Viral Causes of Pharyngitis*

Virus

Associated Disorder or Symptom

Occurrence in Pharyngitis

Rhinovirus

Common cold

Common

Coronavirus

Common cold

Common

Adenovirus

Pharyngoconjunctival fever and acute respiratory disease

Common in military recruits and boarding schools

Herpes simplex virustypes 1 and 2

Gingivostomatitis

Common

Parainfluenza virus

Cold and croup

Common in children

Coxsackievirus A

Herpangina (high fever, vomiting, diarrhea, abdominal pain) and hand-foot-and-mouth disease

Common

Influenza A and B viruses

Influenza

Common during flu season

Respiratory syncytial virus

Bronchiolitis and croup

Common in children

Epstein-Barr virus

Infectious mononucleosis

Common in adolescents during winter

Cytomegalovirus

CMV mononucleosis

Less common

Human immunodeficiency virus

Primary HIV infection

Infrequent (homosexual males and heterosexual females at highest risk)

*Viruses are the most common cause of pharyngitis.

 

Manifestations

Fever, sore throat, edema, and hyperemia of the tonsils and pharyngeal walls are common findings in patients with viral and bacterial causes of pharyngitis. Other findings strongly suggest that a viral, rather than a bacterial, agent cause pharyngitis and include conjunctivitis, cough, coryza, hoarseness, and diarrhea; anterior stomatitis and discrete ulcerative lesions; and viral exanthem.

 

Patients with S pyogenes pharyngitis commonly present with fever and severe pain upon swallowing (generally of sudden onset). Headache, nausea and vomiting, and abdominal pain may also be present, especially in children. On examination, patients have tonsillopharyngeal erythema, with or without exudate, and tender, enlarged anterior cervical lymph nodes (lymphadenitis). They may also have a beefy red and swollen uvula; petechiae on the palate; excoriated nares (usually in children); and a scarlatiniform rash. However, none of these findings, except the scarlet fever rash, are specific for S pyogenes pharyngitis. 

 

If untreated, a patient with S pyogenes pharyngitis can develop suppurative and nonsuppurative complications. Suppurative complications include peritonsillar abscess, cervical lymphadenitis, and mastoiditis. The nonsuppurative complications include acute glomerulonephritis and rheumatic fever.

 

Acute glomerulonephritis is defined as the sudden onset of hematuria, proteinuria, and red blood cell casts. The patient will usually present with hypertension, edema, and impaired renal function.

 

Rheumatic fever is more likely to occur in children with S pyogenes pharyngitis than in adults with this bacterial infection. Rheumatic fever presents as a diverse set of clinical manifestations with onset of symptoms occurring within a few days to 5 weeks after a strep throat infection. A patient with rheumatic fever first presents with fever (38–40°C) and painful swelling of several joints such as the knees, elbows, or wrists. Severe rheumatic fever can result in damage to the valves of the heart.

 

Epidemiology

 

Pathogenesis

In viral pharyngitis, viruses gain access to the mucosal cells lining the nasopharynx and replicate in these cells. Damage to the host is often caused by damage to the cells where the viruses are replicating.

 

In bacterial pharyngitis, S pyogenes attaches to the mucosal epithelial cells using M protein, lipoteichoic acid, and fibronectin-binding protein (protein F). It has a capsule composed of hyaluronic acid that prevents phagocytosis by host macrophages; because the hyaluronic acid in the bacterial capsule is identical to host hyaluronic acid. The capsule facilitates bacterial survival by covering the bacterial antigens. Extracellular factors produced by S pyogenes during the infection include protease and hyaluronidase. These extracellular factors assist the bacteria in invading the mucosa. Direct extension to other sites can occur but due to the use of antibiotic therapy, this is now quite rare.

 

Nonsuppurative lesions resulting in rheumatic fever and glomerulonephritis still occur following throat infections caused by S pyogenes. It is believed that several bacterial antigens from S pyogenes share antigenic epitopes with the heart and renal tissues. An autoimmune reaction occurs in some patients following production of an immune response to these cross-reactive bacterial antigens and damages the patient’s heart or kidneys. Note: Rheumatic fever and glomerulonephritis can occur after an episode of pharyngitis; only glomerulonephritis occurs after skin infections (e.g., impetigo).

Diagnosis

Viral infections of the throat are rarely cultured because of the mild self-limiting nature of the disease and the cost involved in culturing the pathogens. There are fewer cases of bacterial infections of the throat (compared to viral pharyngitis); however, delaying treatment of S pyogenes pharyngitis beyond 9 days after symptoms begin increases the patient’s chances of developing rheumatic fever and suppurative complications (e.g., peritonsillar abscess, mastoiditis). Therefore, strategies for diagnosis of acute pharyngitis infections are primarily directed at identifying patients with S pyogenes pharyngitis who require antimicrobial therapy, as well as avoiding unnecessary treatment of patients diagnosed with acute viral pharyngitis. 

 

The best means of  determining which etiologic agent is causing the pharyngitis is to swab the patient’s throat, culture the sample on blood agar plates, and demonstrate the growth of b-hemolytic colonies that are catalase-negative, gram-positive cocci and are sensitive to bacitracin (A disc). S pyogenes rapid antigen detection tests are available and used clinically; however, these tests are not as sensitive as cultures.

 

Throat cultures are not necessary for proper diagnosis of all cases of pharyngitis, and this is especially true for adults. If an adult has clinical and epidemiologic features (e.g., cough, coryza, conjunctivitis, diarrhea) highly suggestive of a viral etiology, further testing is not needed (Table URI-6).

 

However, if the patient has clinical and epidemiologic features highly suggestive of a bacterial etiology then a rapid antigen detection test can be utilized. If the result of the rapid antigen test is negative then no further testing is needed and the patient is highly likely to have a viral pharyngitis. NO antibiotic or culture for S pyogenes is required. If the rapid antigen test is positive then the patient should be given antimicrobial therapy (e.g., penicillin).

 

Table URI-6. Clinical and Epidemiologic Findings Useful in the Diagnosis of Pharyngitis

Epidemiologic findings suggestive of Streptococcus pyogenes as the etiologic agent

Patient aged 5–15 years

Presentation in winter or early spring

History of exposure

Sudden onset of signs and symptoms

Clinical findings suggestive of Streptococcus pyogenes as the etiologic agent

Sore throat

Fever

Headache

Nausea, vomiting, and abdominal pain

Inflammation of pharynx and tonsils

Patchy discrete exudate

Tender, enlarged anterior cervical nodes

Features suggestive of a virus as the etiologic agent

Conjunctivitis

Coryza

Cough

Diarrhea

Note: These findings, either individually or collectively, cannot definitively predict the presence of S pyogenes pharyngitis. They can identify persons with a high probability of being diagnosed with S pyogenes pharyngitis (and for whom throat culture or rapid antigen detection testing is indicated) or a low probability of S pyogenes pharyngitis (neither culture nor rapid antigen detection testing is necessary).

Children younger than 18 years of age are more likely to develop S pyogenes pharyngitis, and are more likely to develop suppurative and nonsuppurative complications if not treated. Therefore, if a child is likely to have developed S pyogenes pharyngitis, as determined clinically and epidemiologically (see Table URI-6), further testing with rapid antigen detection tests and throat culture is indicated. If the result of the rapid antigen detection test is positive, a throat culture is not needed and the child should be treated with antibiotics. If the result of the rapid antigen detection test is negative, a throat culture should also be performed. A prescription for penicillin should be given if the result of either test is positive. If both tests are negative then the patient does not need an antibiotic.

 

The Modified Centor Scoring System is a clinical scoring system for streptococcal pharyngitis has been developed and is used by some clinicians; (Centor RM et al Pharyngitis management: defining the controversy. J Gen Intern Med. 2007 Jan;22(1):127-30; McIsaac WJ, Kellner JD, Aufricht P, Vanjaka A, Low DE. Empirical validation of guidelines for the management of pharyngitis in children and adults. JAMA. 2004 Apr 7;291(13):1587-95). YOU DO NOT NEED TO MEMORIZE THIS FOR THE EXAM.


 

 

Modified Centor Scoring System

Criteria

Points

Temperature > 38 degree C

1

Absence of cough

1

Swollen, tender anterior cervical nodes

1

Tonsilar swelling or exudate

1

Age (years) 3-14

1

15-44

0

> 45

-1

Rheumatic fever is a nonsuppurative complication of S pyogenes pharyngitis and resembles a number of other diseases that affect the joints (e.g., rheumatoid arthritis, systemic lupus erythematosus, and serum sickness). Diagnosis of this disease and the use of the Jones Criteria will be described in the Heart and Pericardial Infection lectures.

 

Acute glomerulonephritis is defined as the sudden onset of hematuria, proteinuria, and red blood cell casts. The patient will usually present with hypertension, edema, and impaired renal function.

 

Therapy and Prevention

All patients with acute pharyngitis should be offered appropriate doses of antipyretics, analgesics, and supportive care.

 

Viral pharyngitis is treated with analgesics (e.g., acetaminophen), and warm saline gargles. These treatments will help lessen the pain. Fluids to avoid dehydration should be encouraged. Susceptible persons should be encouraged to limit contact with infected persons. An adenovirus vaccine is available for military personnel, but it is not warranted for use in the general population.

 

S pyogenes pharyngitis requires the use of an antimicrobial agent in addition to the treatments mentioned above for viral pharyngitis. Antimicrobial treatment has been shown to limit contiguous spread (e.g., peritonsillar abscess, cervical lymphadenitis, mastoiditis); prevent development of acute rheumatic fever (if given within 9 days of the appearance of symptoms); improve clinical signs and symptoms (if given within 2 days of the appearance of symptoms); rapidly decrease infectivity and thus reducing transmission of the bacterium to close-contacts (e.g., family, classmates); and allow for a rapid resumption to the patient’s usual activities. Penicillin remains the drug of choice to treat S pyogenes pharyngitis; erythromycin is the drug of choice for patients allergic to penicillin. Patients should be encouraged to limit contact with uninfected persons.

 

Treatment of rheumatic fever includes antimicrobials to eliminate the S pyogenes resident in the pharynx and anti-inflammatory agents to suppress the clinical manifestations of the disease. Recurrence of rheumatic fever is more likely in patients who have had a previous episode of S pyogenes pharyngitis. Patients who have recovered from a bout of rheumatic fever should be protected from a second infection due to S pyogenes by chemoprophylaxis with a monthly dose of penicillin. This chemoprophylaxis should continue throughout the patient’s childhood years. If permanent damage occurs to the heart, chemoprophylaxis should continue for the life of the patient.

LEMIERRE’S DISEASE- postanginal septicemia

 

A rare anaerobic infection usually caused by Fusobacterium necrophorum. In adolescents and young adults the diseases starts as a sore throat (may have exudative tonsillitis or peritonsillar abscess). The infection goes into the deep pharyngeal tissue with the organisms draining into the lateral pharyngeal space containing the carotid artery and the internal jugular vein. Septic thrombophlebitis of the internal jugular vein causes pain, dysphagia, and neck swelling and stiffness. Sepsis occurs 3-10 days after the sore throat starts. Infection can spread to the lungs and other distant sites. Sometimes mediastinitis can occur following infection of the carotid sheath and extension of the infection into the posterior mediastinum. Infection can get into the carotid artery with early signs of small bleeds into the mouth. Mortality rate is up to 50%. Treatment involves intravenous antibiotics (penicillin G or clindamycin) and surgical drainage of any purulent collections.


DIPHTHERIA

Diphtheria is a bacterial disease that is now rarely seen in the US because of successful universal vaccination. The vaccine does not affect the ability of the bacteria to colonize the oropharynx, but rather induces antibody production to inhibit diphtheria toxin. If vaccination were no longer available, diphtheria could once again become a common disease.

 

Etiology

 

Corynebacterium diphtheriae is irregularly staining gram-positive, rod-shaped bacteria. Only strains of C diphtheriae that have toxin-producing lysogenic bacteriophage (b phage) can cause diphtheria.

 


Manifestations

 

Diphtheria results in pharyngeal pain, formation of a pseudomembrane seen on the tonsils and back of the oropharynx, regional lymphadenopathy (“bull neck” appearance), edema of the surrounding tissues, fetid breath, low-grade fever, and cough. Airway obstruction can occur, and findings of tachypnea, stridor, and cyanosis are seen. The toxin can damage the cranial nerves and the heart, causing neurologic abnormalities (e.g., palatine palsy, difficulty swallowing, nasal regurgitation of liquids) and myocarditis.

 

Epidemiology

 

 

Pathogenesis

 

C diphtheria colonies the oropharynx and remains localized on the mucosal surfaces. Only C diphtheriae lysogenic for the bacteriophage (beta phage) carrying the toxin gene causes diphtheria. Damage to the pharynx is caused by the diphtheria toxin, which kills the mucosal cells by adenosine diphosphate ribosylation of elongation factor II and terminating protein synthesis. An inflammatory response to cell death and the dead cells form the pseudomembrane. The toxin can also bind to and damage the heart and nerve cells. The major complications of the disease are myocarditis and cranial nerve damage. Myocarditis is the more important of the two complications and causes the highest mortality. Cranial nerves are most sensitive to the toxin, resulting in difficulty swallowing and in nasal regurgitation of liquids.

 

Diagnosis

 

Diagnosis of diphtheria includes observation of a pseudomembrane and bleeding upon removal of the membrane and severe cervical lymphadenopathy. Neurologic abnormalities such as palatine palsy, difficulty swallowing, and nasal regurgitation of fluids are important clues in correctly diagnosing diphtheria. The oropharynx should be swabbed and samples cultured for C diphtheriae. The C diphtheriae strain isolated by culture should be assayed for diphtheria toxin production using the Elek test (immunodiffusion assay) or by polymerase chain reaction (PCR).

 

Treatment and Prevention

 

A patient with diphtheria should be hospitalized, placed in isolation, and immediately treated with antiserum to the toxin. The most urgent task is giving the antiserum to neutralize the toxic affects of the diphtheria toxin. The second most urgent task is antimicrobial treatment with penicillin or erythromycin. The patient should also be given diphtheria vaccine to ensure immunity to the disease. Active immunization with the DTaP vaccine for children and the DT vaccine for adults will serve as protection from diphtheria.

 


Send comments and email to Dr. Neal R. Chamberlain, nchamberlain@atsu.edu
Revised 8/21/14
©2014 Neal R. Chamberlain, Ph.D., All rights reserved.