19 Lower respiratory tract infections
Diphtheria
Diphtheria is caused by toxin-producing strains of Corynebacterium diphtheriae and can cause life-threatening respiratory obstruction
Diphtheria is now rare in resource-rich countries due to widespread immunization with toxoid (see Ch. 34), but it is still common in resource-poor countries. Non-toxigenic strains occur in the normal pharynx, but bacteria producing the extracellular toxin (exotoxin; see Ch. 2) must be present to cause disease. They can colonize the pharynx (especially the tonsillar regions), the larynx, the nose and occasionally the genital tract, and in the tropics or in indigent people with poor skin hygiene, the skin.

Figure 19.1 Pharyngeal diphtheria. Characteristic diphtheria ‘false membrane’ in a child, with local inflammation.
(Courtesy of Norman Begg.)
Diphtheria toxin can cause fatal heart failure and a polyneuritis
The toxin (Box 19.1 and Fig. 19.2) is absorbed into the lymphatics and blood, and has several effects:
• Constitutional upset, with fever, pallor, exhaustion.
• Myocarditis, usually within the first 2 weeks. Electrocardiographic changes are common and cardiac failure can occur. If this is not lethal, complete recovery is usual.
• Polyneuritis, which may occur after the onset of illness, due to demyelination. It may, for instance, affect the 9th cranial nerve, resulting in paralysis of the soft palate and regurgitation of fluids.
Box 19.1 Lessons in Microbiology
Whooping cough
B. pertussis infection is associated with the production of a variety of toxic factors
• Pertussis toxin, which resembles diphtheria and other toxins (see Chs 17 and 18) in being a subunit toxin with an active (A) unit and a binding (B) unit. The A unit is an adenosine diphosphate (ADP)-ribosyl transferase, which catalyses the transfer of ADP-ribose from nicotinamide adenine dinucleotide (NAD) to host cell proteins. The functional consequence of this is a disruption of signal transduction to the affected cell, but the toxin probably has other effects on the cell surface as well.
• Adenylate cyclase toxin, which is a single peptide that can enter host cells and cause them to increase their cyclic adenosine monophosphate (cAMP) to supraphysiologic levels. In neutrophils, this results in an inhibition of defence functions such as chemotaxis, phagocytosis and bactericidal killing. This toxin may also be responsible for the haemolytic properties of B. pertussis.
• Tracheal cytotoxin, which is a cell wall component derived from the peptidoglycan of B. pertussis that specifically kills tracheal epithelial cells (see Ch. 2).
• Endotoxin, which differs from the classic endotoxin of other Gram-negative rods, but has functional similarities and may play a role in the pathogenesis of infection.

Figure 19.3 Chest radiograph showing patchy consolidation and collapse of the right middle lobe in whooping cough.
(Courtesy of J.A. Innes.)
Acute bronchitis
Acute bronchitis is an inflammatory condition of the tracheobronchial tree, usually due to infection
• With influenza virus infection, it may be extensive and leave the host prone to secondary bacterial invasion (post-influenza pneumonia; see below).
• With Mycoplasma pneumoniae infection, specific attachment of the organism to receptors on the bronchial mucosal epithelium (Fig. 19.4) and the release of toxic substances by the organism results in sloughing of affected cells. There is a 4-yearly epidemic cycle that normally occurs 2 years after the Olympic Games. A dry cough is the most prominent presentation, and treatment is largely symptomatic. However, it can cause pneumonia and complications involving other organs, such as hepatitis, encephalitis, arthralgia, skin lesions and haemolytic anaemia. Treatment involves antibiotics such as tetracyclines or macrolides.
Bronchiolitis
Respiratory syncytial virus infection
Respiratory syncytial virus RNA is detectable in throat swab specimens, and ribavirin is indicated for severe disease
Molecular methods, such as PCR, used to detect RSV RNA in throat swab specimens, have a higher diagnostic sensitivity than immunofluorescence (Fig. 19.5) or enzyme-linked immunosorbent assay (ELISA) methods (see Ch. 32), detecting RSV-specific antigens in smears of exfoliated cells obtained by nasopharyngeal aspiration. However, virus isolation is less helpful due to the time taken to detect a cytopathic effect, and success depends on inoculating respiratory secretions as soon as possible into cell cultures.
Hantavirus pulmonary syndrome (HPS)
Ribavirin treatment may be successful if initiated at an early stage in the disease course.
Pneumonia
The respiratory tract has a limited number of ways in which it can respond to infection
• Lobar pneumonia refers to involvement of a distinct region of the lung. The polymorph exudate formed in response to infection clots in the alveoli and renders them solid. Infection may spread to adjacent alveoli until constrained by anatomic barriers between segments or lobes of the lung. Thus one lobe may show complete consolidation.
• Bronchopneumonia refers to a more diffuse patchy consolidation, which may spread throughout the lung as a result of the original pathologic process in the small airways.
• Interstitial pneumonia involves invasion of the lung interstitium and is particularly characteristic of viral infections of the lungs.
• Lung abscess, sometimes referred to as necrotizing pneumonia, is a condition in which there is cavitation and destruction of the lung parenchyma.
A wide range of microorganisms can cause pneumonia
Age is an important determinant (Table 19.1):
• Most childhood pneumonia is caused either by viruses or by bacteria invading the respiratory tract secondary to viral infection, e.g. after measles infection. Neonates born to mothers with genital Chlamydia trachomatis infection may develop a chlamydial interstitial pneumonitis (see Ch. 21) resulting from colonization of the respiratory tract during birth.
• In the absence of an underlying disorder such as cystic fibrosis, pneumonia is unusual in older children. Children and young adults with cystic fibrosis are very prone to lower respiratory tract infection, caused characteristically by Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa.
• The cause of pneumonia in adults depends upon a number of risk factors such as age, underlying disease and exposure to pathogens through occupation, travel or contact with animals.
Table 19.1 Causes of pneumonia related to age
Children | Adults |
---|---|
Mainly viral (e.g. respiratory syncytial virus, parainfluenza) or bacterial secondary to viral respiratory infection (e.g. after measles) | Bacterial causes more common than viral |
Neonates may develop interstitial pneumonitis caused by Chlamydia trachomatis acquired from the mother at birth | Aetiology varies with age, underlying disease, occupational and geographic risk factors |
Pneumonia in children is more often viral in origin or bacterial secondary to a viral respiratory infection. In adults, bacterial pneumonia is more common.
Viral pneumonias show a characteristic interstitial pneumonia on chest radiography more often than bacterial pneumonias (see Fig. 19.6C), and for the sake of clarity are described separately below. Infections with RSV have been described earlier in this chapter, and opportunist pathogens, such as Pneumocystis jirovecii, associated specifically with pneumonia in the immunocompromised, are described in Chapter 30.
Bacterial pneumonia
A variety of bacteria cause primary atypical pneumonia
When penicillin, an effective antibiotic treatment for pneumococcal infection, became widely available, a significant proportion of cases of pneumonia failed to respond to this treatment and were labelled ‘primary atypical pneumonia’. ‘Primary’ refers to pneumonia occurring as a new event, not secondary to influenza, for example, and ‘atypical’ to the fact that Strep. pneumoniae is not isolated from sputum from such patients, the symptoms are often general as well as respiratory, and the pneumonia fails to respond to penicillin or ampicillin. The causes of atypical pneumonia include Mycoplasma pneumoniae, Chlamydophila (formerly Chlamydia) pneumoniae and Chlamydophila (formerly Chlamydia) psittaci, Legionella pneumophila and Coxiella burnetii. The relative importance of these pathogens varies in different studies (Table 19.2). Infection with Chlamydophila pneumoniae is common. About 50% of adults have antibodies, and in the USA it causes up to 300 000 cases of pneumonia each year in adults. Mycoplasma pneumoniae and Chlamydophila pneumoniae appear to be solely human pathogens, whereas Chlamydophila psittaci and Coxiella burnetii are acquired from infected animals, and Legionella pneumophila is acquired from contaminated environmental sources (see Fig. 19.7).
Patients with pneumonia usually present feeling unwell and with a fever
Signs and symptoms of a chest infection include:
• chest pain, which may be pleuritic in nature (pain on inspiration)
• a cough, which may produce sputum
Pneumonia is the most common cause of death from infection in the elderly
The usual laboratory procedures on sputum specimens from patients with pneumonia are Gram stain and culture
Examination of the Gram-stained sputum (see Ch. 32) can give a presumptive diagnosis within minutes if the film reveals a host response in the form of abundant polymorphs and the putative pathogen, e.g. Gram-positive diplococci characteristic of Streptococcus pneumoniae (Fig. 19.8). The presence of organisms in the absence of polymorphs is suggestive of contamination of the specimen rather than infection, but it is important to remember that immunocompromised patients may not be able to mount a polymorph leukocyte response. Also, remember that the causative agents of atypical pneumonia, with the exception of Legionella pneumophila (Fig. 19.9), will not be seen in Gram-stained smears.
Microbiologic diagnosis of atypical pneumonia is usually confirmed by serology
Table 19.3 Serological diagnosis of ‘atypical’ pneumonia
Pathogen | Test |
---|---|
Mycoplasma pneumoniae | Complement fixation test (CFT), IgM by latex agglutination or ELISA |
Legionella pneumophila | Urinary antigen test or rapid microagglutination test |
Chlamydophila pneumonia Chlamydophila psittaci | Microimmunofluorescence or ELISA using species-specific antigens |
Coxiella burnetii | CFT (phase I and phase II antigens) |
Several of the bacterial causes of pneumonia are difficult to grow in the laboratory, so examination of the patient’s serum for specific antibodies is the usual method of diagnosis. It is always better to demonstrate a rising titre between acute- and convalescent-phase sera than to rely on a single sample. ELISA, enzyme-linked immunosorbent assay.
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