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LECTURE NOTES: IMMUNOLOGY/INFECTIOUS DISEASES (NUS 214)

INFECTIOUS DISEASES OF THE RESPIRATORY SYSTEM

INTRODUCTION:

Respiratory tract infections (RTIs) refers to any of a number of infectious diseases involving the

respiratory tract (nose, sinuses, throat, airways or lungs).

They're usually caused by viruses, but can also be caused by bacteria. RTIs are thought to be one

of the main reasons why people visit hospitals or pharmacies. The common cold is the most

widespread RTI.

Pharynx

Healthcare professionals generally make a distinction between:

 Upper respiratory tract infections – which affect the nose, sinuses and throat

 Lower respiratory tract infections – which affect the airways and lungs
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Children tend to get more upper RTIs than adults because they haven't built up immunity

(resistance) to the many viruses that can cause these infections.

RTIs can spread in several ways. If you have an infection such as a cold, tiny droplets of fluid

containing the cold virus are launched into the air whenever you sneeze or cough. If these are

breathed in by someone else, they may also become infected. Infections can also be spread

through indirect contact. For example, if you have a cold and you touch your nose or eyes before

touching an object or surface, the virus may be passed to someone else when they touch that

object or surface.

The best way to prevent spreading infections is to practice good hygiene, such as regularly

washing your hands with soap and warm water.

A. UPPER RESPIRATORY INFECTIONS

Although some disagreement exists on the exact boundary between the upper and lower

respiratory tracts, the upper respiratory tract is generally considered to be the airway above the

glottis or vocal cords. This commonly includes the common cold, tonsillitis, pharyngitis,

laryngitis, sinusitis, and otitis media.

 The common cold - Inflammation of the nares, pharynx, uvula, and tonsils

 Tonsillitis - Inflammation (infection) of the tonsils and tissues at the back of the throat

 Pharyngitis - Inflammation (infection) of the pharynx

 Laryngitis - Inflammation (infection) of the larynx (voice box)

 Sinusitis - Inflammation (infection) of the sinuses

 Otitis media - Inflammation of the middle ear.

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1) COMMON COLD (NASOPHARYNGITIS).

a) Etiology (cause and origin): Common colds are the most predominant cause of all

respiratory infections and are the leading cause of patient visits to the physician, as well as

work and school absenteeism. Most colds are caused by viruses.

Rhinoviruses, Coronaviruses, parainfluenza viruses, respiratory syncytial virus, adenoviruses

and influenza viruses have all been linked to the common cold syndrome. All of these

organisms show seasonal variations in incidence. The cause of 30% to 40% of cold

syndromes has not been determined.

Rhinitis is the most common manifestation of the common cold. It is characterized by

variable fever, inflammatory edema of the nasal mucosa, and an increase in mucous

secretions.

b) Pathogenesis: The viruses appear to act through direct invasion of epithelial cells of the

respiratory mucosa, but whether there is actual destruction and removing of these cells or

loss of ciliary activity depends on the specific organism involved.

c) Diagnosis: The diagnosis of a common cold is usually based on the symptoms (lack of fever

combined with symptoms of localization to the nasopharynx). Unlike allergic rhinitis,

eosinophils are absent in nasal secretions. Although it is possible to isolate the viruses for

definitive diagnosis, that is rarely necessary.

d) Prevention and Treatment: Treatment of the uncomplicated common cold is generally

suggestive. Decongestants, antipyretics, fluids and bed rest usually suffice. Restriction of

activities to avoid infecting others, along with good hand washing, are the best measures to

prevent spread of the disease. No vaccine is commercially available for cold prophylaxis.
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2) TONGSILLITIS:

At the back of your throat, two masses of tissue called tonsils act as filters, trapping germs that

could otherwise enter your airways and cause infection. They also produce antibodies to fight

infection. But sometimes the tonsils themselves become infected. Overwhelmed by bacteria or

viruses, they swell and become inflamed, a condition known as tonsillitis.

Tonsillitis is common, especially in children. The condition can occur occasionally or recur

frequently.

a) Etiology: Bacterial and viral infections can cause tonsillitis. A common cause is

Streptococcus (strep) bacteria. Other common causes include: Adenoviruses, Influenza virus,

Epstein-Barr virus, Parainfluenza viruses, Enteroviruses, and Herpes simplex virus

The main symptoms of tonsillitis are inflammation and swelling of the tonsils, sometimes

severe enough to block the airways. Other symptoms include:

 Throat pain or tenderness

 Redness of the tonsils

 Painful blisters or ulcers on the throat

 Difficulty swallowing or breathing through the mouth

 Fever, chills, headache and bad breath

 Nausea, vomiting and abdominal pain (In children).

b) Diagnosis: Diagnosis is based on a physical examination of your throat. Your doctor may

also take a throat culture by gently swabbing the back of your throat. The culture will be sent

to a laboratory to identify the cause of your throat infection.

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c) Prevention: Tonsillitis is highly contagious. To decrease your risk of getting tonsillitis, stay

away from people who have active infections. Wash your hands often, especially after

coming into contact with someone who has a sore throat, or is coughing or sneezing. If you

have tonsillitis, try to stay away from others until you are no longer contagious.

d) Treatment: Treatment for tonsillitis will depend in part on the cause. To determine the

cause, your doctor may perform a rapid strep test or throat swab culture. Both tests

involve gently swabbing the back of the throat close to the tonsils with a cotton swab. A lab

test can detect a bacterial infection. A viral infection will not show on the test, but may be

assumed if the test for bacteria is negative. In some cases, the physical findings are

convincing enough to diagnose a probable bacterial infection. In these cases, antibiotics may

be prescribed without performing a rapid strep test.

If the tonsillitis is caused by a virus, antibiotics won't work and your body will fight off the

infection on its own. In the meantime, there are things you can do to feel better, regardless of

the cause. They include:

 Get enough rest

 Drink warm or very cold fluids to ease throat pain

 Gargle with warm salt water

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 Take over-the-counter pain relievers such as acetaminophen or ibuprofen.

Surgery to remove the tonsils is called a tonsillectomy. This was once a very common

procedure. However, tonsillectomies today are only recommended for people who experience

chronic or recurrent tonsillitis. Surgery is also recommend to treat tonsillitis that doesn’t respond

to other treatment, or tonsillitis that causes complications. Most tonsillectomies involve using a

conventional scalpel to remove the tonsils; however there are many alternatives to this traditional

method. Increasingly doctors are using techniques such as lasers, radio waves, ultrasonic energy,

or electrocautery to cut, burn, or evaporate away enlarged tonsils.

3) PHARYNGITIS

Pharyngitis is inflammation of the pharynx, which is in the back of the throat. It is most often

referred to simply as “sore throat”. Pharyngitis can also cause scratchiness in the throat and

difficulty swallowing. Pharyngitis-induced sore throat is one of the most common reasons for

doctor visits. More cases of pharyngitis occur during the colder months of the year. It’s also one

of the most common reasons why people stay home from work. In order to properly treat a sore

throat, it’s important to identify its cause. Pharyngitis may be caused by bacterial or viral

infections.

a) Etiology: The etiology can be bacterial, viral and fungal infections as well as noninfectious

etiologies such as smoking. Most cases are due to viral infections and accompany a common

cold or influenza. Type A coxsackieviruses can cause a severe ulcerative pharyngitis in

children, and adenovirus and herpes simplex virus, although less common, also can cause

severe pharyngitis. Pharyngitis is a common symptom of Epstein-Barr virus and

cytomegalovirus infections.
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Candida albicans, which causes oral candidiasis or thrush, can involve the

pharynx, leading to inflammation and pain.

b) Pathogenesis: As with common cold, viral pathogens in pharyngitis appear to invade the

mucosal cells of the nasopharynx and oral cavity, resulting in edema and hyperemia of the

mucous membranes and tonsils. Bacteria attach to and, in the case of group A beta-hemolytic

streptococci, invade the mucosa of the upper respiratory tract. Many clinical manifestations

of infection appear to be due to the immune reaction to products of the bacterial cell. In

diphtheria, a potent bacterial exotoxin causes local inflammation and cell necrosis.

c) Clinical Manifestations: Pharyngitis usually presents with a red, sore, or “scratchy” throat.

An inflammatory exudate or membranes may cover the tonsils and tonsillar pillars. Vesicles

or ulcers may also be seen on the pharyngeal walls. Depending on the pathogen, fever and

systemic manifestations such as malaise, myalgia, or headache may be present. Anterior

cervical lymphadenopathy is common in bacterial pharyngitis and difficulty in swallowing

may be present.

d) Diagnosis: The goal in the diagnosis of pharyngitis is to identify cases that are due to group

A beta-hemolytic streptococci, as well as the more unusual and potentially serious infections.

Culture, serological testing, gene probing and PCR (not routine) are used for diagnosis.

e) Prevention: Maintaining proper hygiene can prevent many cases of pharyngitis. To prevent

pharyngitis:

 Avoid sharing food, drinks, and eating utensils

 Avoid individuals who are sick

 Wash your hands often, especially before eating and after coughing or sneezing

 Use alcohol-based hand sanitizers when soap and water aren’t available
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 Avoid smoking and inhaling secondhand smoke

f) Treatment: Symptomatic treatment is recommended for viral pharyngitis. The exception is

herpes simplex virus infection, which can be treated with acyclovir if clinically warranted or

if diagnosed in immunocompromised patients. The specific antibacterial agents will depend

on the causative organism, but penicillin G is the therapy of choice for streptococcal

pharyngitis. Mycoplasma and chlamydial infections respond to erythromycin, tetracyclines

and the new macrolides.

4) LARYNGITIS.

Laryngitis is when your voice box or vocal cords become inflamed from overuse, irritation, or

infection. The two main types of this condition are chronic (long-term) and acute (short-term)

laryngitis.

A variety of conditions can cause the inflammation that results in laryngitis. These include viral

infections, environmental factors, and in rare cases, bacterial infections.

a) Etiology: Acute laryngitis is a temporary condition caused by an underlying infection or

overuse. Treating the underlying condition will cause the laryngitis to go away. On the other

hand, chronic laryngitis results from long-term exposure to irritants. This type of laryngitis

tends to be more severe and have effects that last longer.

The causes of acute laryngitis include:

 Viral infections.

 Straining vocal cords by talking or yelling more than normal.

 Bacterial infections (rare).

The causes of chronic laryngitis include:

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 Frequent exposure to harmful chemicals or allergens

 Acid reflux

 Frequent sinus infections

 Smoking or being around smokers

 Overusing your voice

 Low-grade yeast infections caused by frequent use of an asthma inhaler

b) Clinical Manifestation: The most common symptoms of laryngitis include:

 Weakened voice or loss of voice

 Hoarse, dry throat and/or dry cough

 Constant tickling or minor throat irritation

In infants and small children, certain symptoms indicate a form of bacterial laryngitis called

croup. Croup, which is inflammation of the throat, can lead to the development of epiglottitis.

Epiglottitis occurs when tissue swells to the point that it begins to close the windpipe. This

condition can be fatal if not treated quickly. Seek immediate medical treatment if your child has:

Trouble swallowing, problems breathing, extra saliva, noisy, high-pitched sounds when

breathing in, fever over 39 °C, and a barking cough.

c) Diagnosis: The main symptom of laryngitis is hoarseness. Laryngitis affects your vocal

cords and voice box. Diagnosis will often start with a visual diagnosis. This involves the use

of a special mirror to view your vocal cords, or by laryngoscopy to magnify the voice box for

easy viewing. During a laryngoscopy, a thin flexible tube with a microscopic camera is stuck

through your mouth or nose in the quest for the following signs of laryngitis:

 Irritation
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 Redness

 Lesions on the voice box

 Widespread swelling, which is a sign of environmental factors causing laryngitis

 Vocal cord swelling only, which is a sign that you’re overusing your vocal cords

If a lesion or other suspicious masses are noticed, a biopsy may be required to rule out throat

cancer. During a biopsy, a small piece of biopsy tissue is removed so it can be examined in a lab.

d) Treatment: If a virus is the reason behind your acute laryngitis, the symptoms will more

than likely disappear without treatment. Bacterial laryngitis can be treated with antibiotics,

although this form of laryngitis is rare.

With most cases of laryngitis, home treatment is all that you need.

 Rest your voice as much as you can. When you have to talk, speak softly but don't

whisper. (Whispering irritates your larynx more than speaking softly.)

 Try not to clear your throat. If you have a dry cough, a non-prescription cough

suppressant may help.

 Add moisture to the air in your home with a humidifier or vaporizer.

 Drink plenty of fluids.

 Don't smoke. And stay away from other people's smoke.

e) Prevention: The best way to keep your vocal cords and voice box healthy is to keep them

moist and free from irritants. You can avoid some irritants by doing the following:

 Avoiding smoking and being around people who smoke

 Limiting your alcohol and caffeine intake

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 Washing your hands regularly to avoid catching colds and upper respiratory

infections

 Trying to avoid toxic chemicals in the workplace if possible

In addition, try to avoid clearing your throat. This increases both mucus production and

irritation.

5) SINUSITIS

Sinusitis is an acute inflammatory condition of one or more of the paranasal sinuses. Infection

plays an important role in this affliction. Sinusitis often results from infections of other sites of

the respiratory tract since the paranasal sinuses are contiguous to, and communicate with, the

upper respiratory tract. Generally, there are 4 sinuses: Maxillary, ethmoid, frontal and

sphenoid.

a) Etiology:
Acute sinusitis most often follows a common cold which is usually of viral etiology. Vasomotor

and allergic rhinitis may also be antecedent to the development of sinusitis. Obstruction of the

sinusal ostia due to deviation of the nasal septum, presence of foreign bodies, growths or tumors

can predispose to sinusitis. Infection of the maxillary sinuses may follow dental extractions or an

extension of infection from the roots of the upper teeth. The most common bacterial agents

responsible for acute sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, and

Moraxella catarrhalis. Other organisms including Staphylococcus aureus, Streptococcus

pyogenes, gram-negative organisms and anaerobes have also been recovered. Chronic sinusitis is

commonly a mixed infection of aerobic and anaerobic organisms.

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b) Pathogenesis:
Infections caused by viruses or bacteria impair the ciliary activity of the epithelial lining of the

sinuses and increased mucous secretions. This leads to obstruction of the paranasal sinusal ostia

which impedes drainage. With bacterial multiplication in the sinus cavities, the mucus is

converted to mucopurulent exudates. The pus further irritates the mucosal lining causing more

edema, epithelial destruction and ostial obstruction. When acute sinusitis is not resolved and

becomes chronic, mucosal thickening results and the development of polyps may result.

c) Clinical manifestations:
The maxillary and ethmoid sinuses are most commonly involved in sinusitis. The frontal

sinuses are less often involved and the sphenoid sinuses are rarely affected. Pain, sensation of

pressure and tenderness over the affected sinus are present. Malaise and low grade fever may

also occur. Physical examination usually is not remarkable with no more than an edematous and

hyperemic nasal mucosa. In uncomplicated chronic sinusitis, a purulent nasal discharge is the

most constant finding. There may not be pain nor tenderness over the sinus areas. Thickening of

the sinus mucosa and a fluid level are usually seen in x-ray films or magnetic resonance imaging

(MRI).

d) Diagnosis:
For acute sinusitis, the diagnosis is made from clinical findings. A bacterial culture of the nasal

discharge can be taken but is not very helpful as the recovered organisms are generally

contaminated by the resident flora from the nasal passage. In chronic sinusitis, a careful dental
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examination, with sinus x-rays may be required. An antral puncture to obtain sinusal specimens

for bacterial culture is needed to establish a specific microbiologic diagnosis.

e) Prevention and Treatment:

Symptomatic treatment with analgesics and moist heat over the affected sinus pain and a

decongestant to promote sinus drainage may suffice.

For antimicrobial therapy, a beta-lactamase resistant antibiotic such as amoxicillin-clavulanate or

a cephalosporin may be used.

For chronic sinusitis, when conservative treatment does not lead to a cure, irrigation of the

affected sinus may be necessary.

Culture from an antral puncture of the maxillary sinus can be performed to identify the causative

organism for selecting antimicrobial therapy. Specific preventive procedures are not available.

6) OTITIS

Infections of the ears are common events encountered in medical practice, particularly in young

children. Otitis externa is an infection involving the external auditory canal while otitis media

denotes inflammation of the middle ear.

a) Etiology:

For otitis externa, the skin flora such as Staphylococcus epidermidis, Staphylococcus aureus, and

occasionally an anaerobic organism, Propionibacterium acnes are major etiologic agents. In a

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moist and warm environment, a diffuse acute otitis externa (Swimmer's ear) may be caused by

Pseudomonas aeruginosa, along with other skin flora. Malignant otitis externa is a severe

necrotizing infection usually caused by Pseudomonas aeruginosa.

For otitis media, the commonest causative bacteria are Streptococcus pneumoniae, Hemophilus

influenzae and beta-lactamase producing Moraxella catarrhalis. Respiratory viruses may play a

role in otitis media but this remains uncertain. Mycoplasma pneumoniae has been reported to

cause hemorrhagic bullous myringitis (inflammation of the eardrum) in an experimental study

among non-immune human volunteers inoculated with M pneumoniae. However, in natural cases

of M pneumonia infection, clinical bullous myringitis or otitis media is uncommon.

b) Pathogenesis:

The narrow and twisted auditory canal is lined by a protective surface epithelium. Factors that

may disrupt the natural protective mechanisms, such as high temperature and humidity, trauma,

allergy, tissue soaking, and an alkaline pH environment, favour the development of otitis

externa. Prolonged immersion in a swimming pool coupled with frequent ear cleansing increases

the risk of otitis externa.

Acute otitis media commonly follows an upper respiratory infection extending from the

nasopharynx via the Eustachian tube to the middle ear. Vigorous nose blowing during a

common cold, sudden changes of air pressure, and perforation of the tympanic membrane also

favor the development of otitis media. The presence of purulent exudate in the middle ear may

lead to a spread of infection to the inner ear and mastoids or even meninges

c) Clinical Manifestations:
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Otitis externa

Furuncles of the external ear, similar to those in skin infection, can cause severe pain and a sense

of fullness in the ear canal. When the furuncle drains, purulent otorrhea may be present. In

generalized otitis externa, itching, pain and tenderness of the ear lobe on traction are present.

Loss of hearing may be due to obstruction of the ear canal by swelling and the presence of

purulent debris. Malignant otitis externa tends to occur in elderly diabetic patients. It is

characterized by severe persistent ear ache, foul smelling purulent discharge and the presence of

granulation tissue in the auditory canal. The infection may spread and lead to osteomyelitis of the

temporal bone or externally to involve the pinna with osteochondritis.

Otitis media

Acute otitis media occurs most commonly in young children. The initial complaint usually is

persistent severe earache (crying in the infant) accompanied by fever, and vomiting. Otologic

examination reveals a bulging, erythematous tympanic membrane with loss of light reflex and

landmarks. If perforation of the tympanic membrane occurs, bloody purulent discharge may be

present. In the event of an obstruction of the Eustachian tube, accumulation of a usually sterile

effusion in the middle ear results in serous otitis media. Chronic otitis media frequently presents

a permanent perforation of the tympanic membrane.

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d) Diagnosis: The diagnosis of both otitis externa and otitis media can be made from history,

clinical symptomatology and physical examinations. Inspection of the tympanic membrane is

an indispensable skill for physicians and health care workers. All discharge, ear wax and

debris must be removed and to perform an adequate otoscopy. In the majority of patients,

routine cultures are not necessary, as a number of good bacteriologic studies have shown

consistently the same microbial pathogens mentioned in the section of etiology. If the patient

is immunocompromised or is toxic and not responding to initial antimicrobial therapy

tympanocentesis (needle aspiration) to obtain middle ear effusion for microbiologic culture

is indicated.

e) Prevention and treatment:

Otitis externa

Topical therapy is usually sufficient and systemic antimicrobials are seldom needed unless

there are signs of spreading cellulitis and the patient appears toxic. A combination of topical

antibiotics such as neomycin sulfate, polymyxin B sulfate and corticosteroids used as

eardrops, is a preferred therapy. In some cases, acidification of the ear canal by applying a

2% solution of acetic acid topically may also be effective. If a furuncle (boil) is present in the

external canal, the physician should allow it to drain spontaneously.

Otitis media

Amoxicillin is an effective and preferred antibiotic for treatment of acute otitis media. Since

beta-lactamase producing H influenzae and M catarrhalis can be a problem in some

communities, amoxicillin-clavulanate is used by many physicians. Oral preparations of

trimethoprim/sulfamethoxazole, second and third generation cephalosporins, tetracyclines

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and macrolides can also be used. When there is a large effusion, tympanocentesis may hasten

the resolution process by decreasing the sterile effusion. Patients with chronic otitis media

and frequent recurrences of middle ear infections may be benefitted by chemoprophylaxis

with once daily oral amoxicillin or trimethoprim/sulfamethoxazole.

B. LOWER RESPIRATORY SYSTEM INFECTIONS

The lower respiratory tract consists of the trachea (wind pipe), bronchial tubes, the bronchioles,

and the lungs. Lower respiratory tract infections (LRIs) are generally more serious than upper

respiratory infections. LRIs are the leading cause of death among all infectious diseases.

Influenza affects both the upper and lower respiratory tracts.

1) BRONCHITIS AND BRONCHIOLITIS

a) Etiology: Bronchitis and bronchiolitis involve inflammation of the bronchial tree. Bronchitis is

usually preceded by an upper respiratory tract infection or forms part of a clinical syndrome in

diseases such as influenza, rubeola, rubella, pertussis, scarlet fever and typhoid fever. Chronic

bronchitis with a persistent cough and sputum production appears to be caused by a combination

of environmental factors, such as smoking, and bacterial infection with pathogens such as H

influenzae and S pneumoniae.

Bronchiolitis is a viral respiratory disease of infants and is caused primarily by respiratory

syncytial virus. Other viruses, including parainfluenza viruses, influenza viruses and

adenoviruses (as well as occasionally M pneumoniae) are also known to cause bronchiolitis.

b) Pathogenesis: When the bronchial tree is infected, the mucosa becomes hyperemic and

edematous and produces abundant bronchial secretions. The damage to the mucosa can range

from simple loss of mucociliary function to actual destruction of the respiratory epithelium,

depending on the organisms(s) involved. Patients with chronic bronchitis have an increase in the
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number of mucus-producing cells in their airways, as well as inflammation and loss of bronchial

epithelium, Infants with bronchiolitis initially have inflammation and sometimes necrosis of the

respiratory epithelium, with eventual sloughing. Bronchial and bronchiolar walls are thickened.

Exudate made up of necrotic material and respiratory secretions and the narrowing of the

bronchial lumen lead to airway obstruction. Areas of air trapping and atelectasis (failure of a

lung to expand properly) develop and may eventually contribute to respiratory failure.

c) Clinical Manifestations: Symptoms of an upper respiratory tract infection with a cough is the

typical initial presentation in acute bronchitis. Mucopurulent sputum may be present, and

moderate temperature elevations occur. Typical findings in chronic bronchitis are an incessant

cough and production of large amounts of sputum, particularly in the morning. Development of

respiratory infections can lead to acute exacerbations of symptoms with possibly severe

respiratory distress.

Coryza (common cold) and cough usually precede the onset of bronchiolitis. Fever is common.

A deepening cough, increased respiratory rate, and restlessness follow. Retractions of the chest

wall, nasal flaring, and grunting are prominent findings. Wheezing or an actual lack of breath

sounds may be noted. Respiratory failure and death may result.

d) Diagnosis: Bacteriologic examination and culture of purulent respiratory secretions should

always be performed for cases of acute bronchitis not associated with a common cold. Patients

with chronic bronchitis should have their sputum cultured for bacteria initially and during

exacerbations. Aspirations of nasopharyngeal secretions or swabs are sufficient to obtain

specimens for viral culture in infants with bronchiolitis. Serologic tests demonstrating a rise in

antibody titer to specific viruses can also be performed. Rapid diagnostic tests for antibody or
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viral antigens may be performed on nasopharyngeal secretions by using fluorescent-antibody

staining, ELISA or DNA probe procedures.

e) Prevention and Treatment: With only a few exceptions, viral infections are treated with

supportive measures. Respiratory syncytial virus infections in infants may be treated with

ribavirin. Amantadine and Rimantadine are available for chemoprophylaxis or treatment of

Influenza type A viruses. Selected groups of patients with chronic bronchitis may receive benefit

from use of corticosteroids, bronchodilators, or prophylactic antibiotics.

2) PNEUMONIA:

Pneumonia is an inflammation of the lung parenchyma. Merging of the lung tissue

may be identified by physical examination and chest x-ray. Numerous factors, including

environmental contaminants and autoimmune diseases, as well as infection, may cause

pneumonia. The various infectious agents that cause pneumonia are categorized in many ways

for purposes of laboratory testing, epidemiologic study and choice of therapy. Pneumonias

occurring in usually healthy persons not confined to an institution are classified as community-

acquired pneumonias. Infections arise while a patient is hospitalized or living in an institution

such as a nursing home are called hospital-acquired or nosocomial pneumonias. Etiologic

pathogens associated with community-acquired and hospital-acquired pneumonias are somewhat

different. However, many organisms can cause both types of infections.

a) Etiology

Bacterial pneumonias
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Streptococcus pneumoniae is the most common agent of community-acquired acute bacterial

pneumonia. Pneumonias caused by other streptococci are uncommon. Streptococcus pyogenes

pneumonia is often associated with a hemorrhagic pneumonitis and empyema.

Community-acquired pneumonias caused by Staphylococcus aureus are also uncommon and

usually occur after influenza or from staphylococcal bacteremia. Infections due to Haemophilus

influenzae and Klebsiella pneumoniae are more common among patients over 50 years old who

have chronic obstructive lung disease or alcoholism.

The most common agents of nosocomial pneumonias are aerobic gram-negative bacilli that

rarely cause pneumonia in healthy individuals. Pseudomonas aeruginosa, Escherichia coli,

Enterobacter, Proteus, and Klebsiella species are often identified. Less common agents causing

pneumonias include Francisella tularensis, the agent of tularemia; Yersinia pestis, the agent of

plague; and Neisseria meningitidis, which usually causes meningitis but can be associated with

pneumonia, especially among military recruits.

Mycobacterium tuberculosis can cause pneumonia. Although the incidence of tuberculosis is low

in industrialized countries, M tuberculosis infections still continue to be a significant public

health problem in the world, particularly among immigrants from developing countries,

intravenous drug abusers, patients infected with human immunodeficiency virus (HIV), and the

institutionalized elderly. Atypical Mycobacterium species can cause lung disease

indistinguishable from tuberculosis.

Legionella species, including L. pneumophila, can cause a wide range of clinical manifestations.

These organisms can survive in water and cause pneumonia by inhalation from aerosolized tap
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water, respiratory devices, air conditioners and showers. They also have been reported to cause

nosocomial pneumonias.

Chlamydia spp noted to cause pneumonitis are C trachomatis, C psittaci and C pneumoniae.

Chlamydia trachomatis causes pneumonia in neonates and young infants. Chlamydia

pneumoniae has been associated with outbreaks of pneumonia in military recruits and on college

campuses.

Viral pneumonias are rare in healthy civilian adults. An exception is the viral pneumonia caused

by influenza viruses, which can have a high mortality in the elderly and in patients with

underlying disease. A serious complication following influenza virus infection is a secondary

bacterial pneumonia, particularly staphylococcal pneumonia. Respiratory syncytial virus can

cause serious pneumonia among infants as well as outbreaks among institutionalized adults.

Other pneumonias and immunosuppression

Cytomegalovirus is well known for causing congenital infections in neonates, as well as in

adults. However, among its manifestations in immunocompromised individuals is a severe and

often fatal pneumonitis. Herpes simplex virus also causes a pneumonia in this population. Giant-

cell pneumonia is a serious complication of measles and has been found in children with

immunodeficiency disorders or underlying cancers who receive live attenuated measles vaccine.

Actinomyces and Nocardia spp can cause pneumonitis, particularly in immunocompromised

hosts.

Among the fungi, Cryptococcus neoformans and Sporothrix schenckii are found worldwide,

whereas Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum and

Paracoccidioides brasiliensis have specific geographic distributions. All can cause pneumonias,
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which are usually chronic and possible clinically inapparent in normal hosts, but are manifested

as more serious diseases in immunocompromised patients. Other fungi, such as Aspergillus and

Candida spp, occasionally are responsible for pneumonias in severely ill or immunosuppressed

patients and neonates.

Pneumocystis carinii produces a life-threatening pneumonia among patients immunosuppressed

by acquired immune deficiency syndrome (AIDS), hematologic cancers, or medical therapy. It is

the most common cause of pneumonia among patients with AIDS when the CD4 cell counts

drop below 200/mm3.

b) Pathogenesis and Clinical Manifestations:

Infectious agents gain access to the lower respiratory tract by the inhalation of aerosolized

material, by aspiration of upper airway flora, or by hematogenous seeding. Pneumonia occurs

when lung defense mechanisms are diminished or overwhelmed. The major symptoms or

pneumonia are cough, chest pain, fever, shortness of breath and sputum production. Patients are

tachycardic (rapid beating of the heart). Headache, confusion, abdominal pain, nausea, vomiting

and diarrhea may be present, depending on the age of the patient and the organisms involved.

c) Diagnosis:

Etiologic diagnosis of pneumonia on clinical grounds alone is almost impossible. Sputum should

be examined for a predominant organism in any patient suspected to have a bacterial pneumonia;

blood and pleural fluid (if present) should be cultured. A sputum specimen with fewer than 10

while cells per high-power field under a microscope is considered to be contaminated with oral

secretions and is unsatisfactory for diagnosis.

Acid-fast stains and cultures are used to identify Mycobacterium and Nocardia spp.
 23

Most fungal pneumonias are diagnosed on the basis of culture of sputum or lung tissue.

Viral infection may be diagnosed by demonstration of antigen in secretions or cultures or by an

antibody response. Serologic studies can be used to identify viruses, M pneumoniae, C. burnetii,

Chlamydia species, Legionella, Francisella, and Yersinia.

d) Prevention and Treatment:

Until the organism causing the infection is identified, decisions on therapy are based upon

clinical history, including history of exposure, age, underlying disease and previous therapies,

past pneumonias, geographic location, severity of illness, clinical symptoms, and sputum

examination. Once a diagnosis is made, therapy is directed at the specific organism responsible.

The pneumococcal vaccine should be given to patients at high risk for developing pneumococcal

infections, including asplenic patients, the elderly and any patients immunocompromised through

disease or medical therapy. Yearly influenza vaccinations should also be provided for these

particular groups. An enteric-coated vaccine prepared from certain serotypes of adenoviruses is

available, but is only used in military recruits. In AIDS patients, trimethoprim/sulfamethoxazole,

aerosolized pentamidine or other antimicrobials can be given for prophylaxis of Pneumocystis

carinii infections.
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INFECTIONS OF THE CIRCULATORY SYSTEM

INTRODUCTION:

The circulatory system includes the cardiovascular system and the lymphatic system. The

lymphatic system consists of the lymph, lymphatic vessels, lymphatic tissue, and lymphatic

organs. The cardiovascular system consists of the heart, blood, and blood vessels. Infection and

inflammation of the cardiovascular system frequently cause cardiac and vascular disease. The

lymphatic system returns excess tissue fluid back to the cardiovascular system and therefore has

direct access to the cardiovascular system. Once microorganisms gain access to either one of the

systems they can spread throughout the body and therefore have the potential to infect any organ

system. In general, bacterial and fungal infections will affect the endocardium (tissue lining of

the heart chambers), causing endocarditis, whereas viral and parasitic infections affect the

myocardium (heart muscle), resulting in myocarditis. Inflammation and infection of the

pericardium (membrane surrounding the heart), called pericarditis, can be caused by bacteria,

viruses, and rarely by fungi.

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1. ENDOCARDITIS

Endocarditis is an inflammation of the endocardium, the lining of the heart or the heart valves.

The condition can be classified as infective if a microorganism is involved, or as non-infective.

Non-infective endocarditis involves the formation of platelet and fibrin thrombi on heart valves

and the surrounding endocardium, in response to trauma, circulating immune complexes,

vasculitis (inflammation of a blood vessel), or a hyper-coagulated state. Infective endocarditis

symptoms may develop slowly (sub-acute) or suddenly and they include the following:

 Fatigue and weakness.

 Fever and chills.

 Night sweats and other excessive sweating.

 Weight loss.

 Muscle aches and pains, joint pain.

 Shortness of breath.

 Blood in the urine, abnormal urine color.

 Red painless skin spots on palms and soles.

The most common cause of infectious endocarditis is Staphylococcus aureus, but it also can be

caused by fungi (Candida). In some cases, no causative organism can be identified.

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2. MYOCARDITIS:

Myocarditis is the inflammation of the myocardium, the muscular portion of the heart, and is

generally caused by viral or parasitic infections. However, it also can be caused by bacterial

infections, as well as by exposure to chemicals, or allergic reactions. The cardiac muscle

becomes weakened and this can result in heart failure. The symptoms of myocarditis are vague,

making the diagnosis difficult. They can include the following:

 Chest pain

 Fever

 Shortness of breath

 Leg swelling

 Arrhythmias

 Congestive heart failure

3. PERICARDITIS:

Pericarditis is the term used to describe inflammation of the pericardium, the saclike membrane

surrounding the heart. The condition is usually a result of complications of a viral infection, but

can also be caused by bacteria and fungi. The symptoms include the following:

 Chest pain

 Breathing difficulty when lying down

 Dry cough

 Ankle, foot, and leg swelling

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 Anxiety, Fatigue and Fever

4. BLOOD-BORNE INFECTIOUS DISEASES

Blood-borne disease is spread by contaminated blood or bodily fluids. Any exposure to blood or

other bodily fluids can transmit infectious disease. Although blood-borne diseases can affect

anyone exposed to infected blood or bodily fluids, the risk of exposure is greater with certain

occupations such as healthcare, emergency response, public safety, teaching, and many others.

Pathogens of primary concern for these professions, are HIV, hepatitis B virus, hepatitis C virus,

and those causing viral hemorrhagic fever (EBOLA, Marburg, Lassa fever virus, and yellow

fever virus). Diseases that are not transmitted directly by blood or by contact with bodily fluids,

but by an insect or other vector, are classified as vector-borne diseases.

5. BACTERIAL INFECTIONS

Once bacteria have access to the circulatory system they become widely dispersed (bacteraemia)

and are capable of infecting a wide range of tissues and organs. If the bacteria in the circulatory

system are not destroyed by the immune system or by antibiotic treatment, they can multiply in

the blood and cause septicemia. Examples of bacterial diseases of the circulatory system are

illustrated below.

Disease Organism Target of Transmission Treatment

infection
Rheumatic Group A Heart, joints, brain, Coughing, Penicillin,
fever Streptococcus spinal cord, skin sneezing, saliva erythromycin, oral
cephalosporin,
vancomycin, oxacillin
Gas Clostridium Extremities, Wound contact Removal of necrotic
gangrene perfringens muscle tissues, and with soil tissue, including
 28

organs amputation

Bacteraemia:

Blood is normally sterile, but microorganisms can enter the blood under a variety of conditions.

Bacteremia is the term used when bacteria are present in the bloodstream. Bacteremia has

various possible causes including infection during dental procedures, catheterization and the

placement of other indwelling devices, surgical procedures, wound infection, and many more. In

general, the presence of bacteria in the blood elicits a strong immune response by circulating

macrophages, the complement system, and lymphocytes, thus preventing bacteria from

multiplying. In addition, the blood is relatively low on iron, a requirement for most bacterial

growth. If the defenses of the immune and circulatory systems fail microbes can undergo

uncontrolled proliferation in the blood, causing a condition called septicemia.

Septicaemia:

Sepsis is a toxic condition caused by the spread of bacteria or bacterial toxins from the site of

infection. Septicemia is sepsis that occurs when bacteria multiply in the bloodstream. Septicemia

is a medical emergency that requires immediate medical treatment. If the condition progresses to

septic shock, the death rate is as high as 50%, depending on the type of organism involved.

Septic shock is the result of hypotension (low blood pressure) despite adequate fluid substitution.

Septicemia develops quickly and the patient becomes extremely ill. Although each individual

may experience symptoms differently, the most common symptoms include the following:

 Loss of appetite
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 Fever and chills

 Lethargic, anxious, or agitated behavior

 Accelerated heart rate and breathing

a) Rheumatic fever:

Rheumatic fever is an inflammatory disease that can develop as a rare complication after a

group A streptococcal infection such as strep throat or scarlet fever. The condition commonly

involves the heart, joints, brain, spinal cord, and skin. In general, rheumatic fever occurs in

children between the ages of 4 and 18 years. Symptoms normally begin several weeks after the

disappearance of localized throat symptoms and vary greatly between individuals, depending on

the parts of the body inflamed. The most common symptoms include the following:

 Joint pain

 Fever

 Chest pain

 Carditis (inflammation of the connective tissue of the heart)

 Rash

 Nodules under the skin

In some children, carditis may not be evident and the inflammation of the heart is recognized

only years later, when heart damage is discovered. Treatment involves long-term antibiotic

administration to eliminate any residual streptococcal infection, anti-inflammatory medication to

reduce inflammation, and also the limiting of physical activity that might aggravate the inflamed
 30

structures. People who do not take low-dose antibiotics continually, especially during the first 3

to 5 years after the first episodes of the disease, will likely experience recurrence of the

condition, resulting in severe heart complications.

b) Gangrene is a complication of necrosis, the decay and death of tissue that is often related to

wounds. If the blood supply to a tissue is interrupted by an infection or ischemia (restriction

of blood supply) gangrene can occur. Gangrene most commonly affects the extremities;

however, it can also occur in muscle tissue and organs. Enzymes released from the dying

cells and tissue will further destroy the surrounding tissues and thus provide a perfect nutrient

environment for many bacterial species. Tissues lacking of blood supply become ischemic

and provide an environment for anaerobic bacteria. Several species of the genus Clostridium,

gram-positive, endospore-forming anaerobes, grow easily under these conditions.

Clostridium is commonly found in soil as well as in the intestinal tracts of humans and

domestic animals. The most frequent species involved in gangrene is C. perfringens, but

other species and several other genera of bacteria can also grow under the conditions

mentioned.

Treatment of gangrene usually entails the removal of necrotic tissue, and in many cases

amputation may be necessary. Because antibiotics cannot reach the ischemic tissue,

antibiotics alone are not effective. In addition to surgery and antibiotics, hyperbaric (high

pressure) oxygen therapy can be used to kill the anaerobic Clostridium causing the condition.

There are different types of gangrene, including the following:

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• Dry gangrene, due to ischemia and generally beginning at the distal portions of a limb such as

in the feet. This condition often occurs in elderly patients with arteriosclerosis, and other persons

with impaired peripheral blood flow, such as diabetic patients.

• Internal gangrene, also called white gangrene, is noticeable by the bleaching of internal tissue,

and is generally contracted after surgery or trauma.

• Wet gangrene occurs in organs lined by mucous membranes such as the mouth, lower

intestinal tract, lungs, and cervix. Although not necessarily associated with moist tissue, bedsores

are also categorized as wet gangrene infections. Toxic products formed by the infecting bacteria

can be absorbed if the affected tissue is not removed, resulting in septicemia, and eventually

death.

• Gas gangrene is caused by bacteria that produce gas within the infected tissue. Toxins

produced by the bacteria will cause necrosis of more tissue, thereby providing further bacterial

growth. If untreated, the condition is fatal.

Gas
gangrene

6. ZOONOTIC INFECTIONS:

Any disease and/or infection that can be transmitted from vertebrate animals to humans is

classified as a zoonosis. More than 200 zoonoses have been described, but not all affect the
 32

circulatory system. Zoonoses may be caused by bacteria, viruses, parasites, and unconventional

agents such as prions.

a) Brucellosis (Undulant Fever).

Brucellosis is an infectious disease that occurs worldwide and is caused by various Brucella

species. Although the condition is found worldwide, it is most common in areas with insufficient

standards for public health and domestic animal health programs. Brucellas are small, gram-

negative, aerobic (or capnophilic) coccobacilli that are adapted to intracellular replication. These

bacteria affect primarily sheep, goats, cattle, deer, elk, pigs, dogs, and other animals. It is

zoonotic and humans become infected by contact with animals or animal products contaminated

with the bacteria. Person-to-person spread of brucellosis is extremely rare, but may occur when

an infected woman is breastfeeding. High-risk groups include abattoir workers, meat inspectors,

animal handlers, veterinarians, and laboratory technicians. In general, the most common cause of

infection is the ingestion of unpasteurized milk or other dairy products.

Clinically, the acute form of brucellosis is nonspecific and represents itself with flulike

symptoms including chills, excessive sweating, fever, sweats, weakness, malaise, anorexia,

headache, abdominal pain, back pain, and joint pain. Severe infections of the central nervous

system or the lining of the heart (endocardium) may occur. Brucellosis can also be chronic, with

symptoms that include undulant fevers, arthritis, chronic fatigue syndrome, and depression.

Treatment with antibiotics is possible but may be difficult, depending on the timing of the

treatment and the severity of the disease. The mortality rate of the disease is low and is usually

associated with endocarditis. Treatment is by Doxycycline plus rifampin for non-pregnant adults

and Trimethoprim-sulfamethoxadole for pregnant women and children under age 8 years.
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7. VECTOR-BORNE INFECTIONS

Vector-borne diseases are generally acquired through the bite of an infected arthropod:

a) Malaria:

Malaria - caused by single-cell parasitic protozoa Plasmodium; transmitted to humans via the

bite of the female Anopheles mosquito; parasites multiply in the liver attacking red blood cells

resulting in cycles of fever, chills, and sweats accompanied by anemia; death due to damage to

vital organs and interruption of blood supply to the brain; endemic in 100, mostly tropical,

countries with 90% of cases and the majority of 1.5 - 2.5 million estimated annual deaths

occurring in sub-Saharan Africa.

b) Dengue fever:

Dengue fever is caused by the dengue virus. Dengue fever is a mosquito-borne (Aedes aegypti)

viral disease associated with urban environments. It manifests as sudden onset of fever and

severe headache; occasionally produces shock and haemorrhage leading to death in 5% of cases.

c) Yellow fever:

Yellow fever is caused by the Yellow fever virus. Yellow fever is a mosquito-borne viral disease

whose severity ranges from influenza-like symptoms to severe hepatitis and hemorrhagic fever.

It occurs only in tropical South America and sub-Saharan Africa, where most cases are reported.

The fatality rate is less than 20%.

d) African Trypanosomiasis (sleeping sickness)

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African Trypanosomiasis is caused by the parasitic protozoa Trypanosoma. It is transmitted to

humans via the bite of bloodsucking Tsetse flies and infection leads to malaise and irregular

fevers and, in advanced cases when the parasites invade the central nervous system, coma and

death. It is endemic in 36 countries of sub-Saharan Africa as cattle and wild animals act as

reservoir hosts for the parasites.

e) Leishmaniasis.

Cutaneous Leishmaniasis is caused by the parasitic protozoa leishmania, transmitted to humans

via the bite of sandflies resulting in skin lesions that may become chronic. It is endemic in 88

countries, 90% of cases occur in Iran, Afghanistan, Syria, Saudi Arabia, Brazil, and Peru. Wild

and domesticated animals as well as humans can act as reservoirs of infection.

f) Bubonic plague:

Plague is a bacterial disease transmitted by fleas normally associated with rats. It is caused by

Yersinia pestis. Person to person airborne transmission also possible. Recent plague epidemics

occurred in areas of Asia, Africa, and South America associated with rural areas or small towns

and villages; manifests as fever, headache, and painfully swollen lymph nodes; disease

progresses rapidly and without antibiotic treatment leads to pneumonic form with a death rate in

excess of 50%.

g) Rift Valley Fever:

 35

Rift Valley fever is a viral disease affecting domesticated animals and humans; transmission

is by mosquito and other biting insects; infection may also occur through handling of

infected meat or contact with blood; Geographic distribution includes eastern and southern

Africa where cattle and sheep are raised; symptoms are generally mild with fever and some

liver abnormalities, but the disease may progress to haemorrhagic fever, encephalitis, or

ocular disease; fatality rates are low at about 1% of cases.