respiratory tract infections essay

Respiratory Tract Infections Case Study

Materials and methods, laboratory report, reference list.

Respiratory tract infections represent the group of infections that cause diseases of the throat, lungs, or airways, depending on the type. Thus, respiratory tract infections are divided into upper respiratory tract infections (URTIs), which cause diseases of the throat, nose, pharynx, and larynx, and lower respiratory tract infections (LRTIs), which cause diseases of the bronchi, trachea, and lungs (Kateete et al. 2010). LRTIs are usually associated with such serious conditions as pneumonia and bronchitis. LRTIs are usually viral in origin, and the pathogens that cause pneumonia and bronchitis include S. pneumonia, H. influenza, M. catarrhalis, S. aureus, and Klebsiella pneumonia (Pesavento et al. 2010). As a result of infections, patients have problems with breathing, and they report having fever and cough among other symptoms. The acute forms of these conditions can cause even the patient’s death if the infection is not treated appropriately (Shrestha, Pokhrel & Mohapatra 2009). In its turn, influenza can affect both URTIs and LRTIs. The H5N1 subtype of the influenza virus can have the most serious negative impact on the patient’s lungs and bronchi (Mishra & Bayer 2013).

In this case, the 59-year-old male has the signs of bronchitis. It is important to note that bronchitis is categorized as the LRTI, and the treatment depends on the pathogen that causes the condition. From this point, further microbiological investigation is necessary because it is significant to determine which bacterium causes bronchitis in the patient and prescribe the appropriate antibiotics to address it while referring to the antibiotics sensitivity testing. In spite of the fact that bronchitis can be caused by a variety of bacteria, the microbiological investigation allows determining the specific pathogen causing the disease development in the concrete patient, and the expected outcome is the discussion of the bacterium and identification of antibiotics to treat the disease effectively.

In order to conduct the microbiological investigation, the following materials were used:

• The sputum sample.
• Three agar plates: Horse blood agar (HBA), MacConkey agar (MAC), and Chocolate agar (CHA).
• Gram staining test.
• Catalase test.
• Coagulase test.
• Deoxyribonuclease (DNase) plate with hydrochloric acid.
• Antimicrobial susceptibility test discs.

The first step in the microbiological investigation was the culturing of the patient’s sputum sample characterized as a heavy purulent one with the help of three agar plates: HBA, CHA, and MAC. The sputum was cultured and incubated for 24 hours under aerobic condition (CO2). These plates were selected because according to Cain (2014), the use of HBA, CHA, and MAC plates contributes to the rapid growth of colonies of bacteria that can be further examined individually. Adegoke and Okoh (2014) also note that under aerobic conditions, many bacteria not only survive but also grow actively.

In 24 hours, the colonies from the three plates were examined to determine the morphology type. The colonies from the HBA plate were taken with the help of a sterile loop in order to conduct the Gram staining test. The Gram stain is important in order to identify the morphology of the bacterium or its type (Kaasch et al. 2014). The same colonies were used in order to conduct the catalase test for the purpose of distinguishing between Staphylococcus and Streptococcus. The catalase test is selected because Staphylococci usually have the enzyme catalase when it is not presented in Streptococci (Cain 2014; Chatterjee et al. 2009).

The next step was to conduct the coagulase test for the purpose of distinguishing between types of Staphylococci. The slide test was conducted in order to identify how the determined Staphylococcus can clot the plasma in order to identify Staphylococcus aureus. To confirm the presence of Staphylococcus aureus, it was reasonable to conduct the DNase test. This test is used for the detection of Staphylococcus aureus to prove the results of the previous tests because Staphylococcus aureus contains such enzyme as DNase (Wiriyachaiporn et al. 2013). The DNase plate was incubated for 24 hours.

When all tests were performed, it was necessary to conduct the antibiotics sensitivity test with the help of antimicrobial susceptibility test discs in order to determine to which types of antibiotics Staphylococcus aureus can be susceptible. Penicillin, gentamicin, chloramphenicol, oxacillin, cefoxitin, and erythromycin were selected for this test because of the high-level resistance of Staphylococcus aureus to many types of antibiotics (Sudhanthiramani, Swetha & Bharathy 2015). The results of the conducted tests are presented in the following section.

The results of testing using HBA, CHA, and MAC plates under aerobic conditions indicate the presence of white and yellow colonies for HBA, white and yellow colonies for CHA, and pinky colonies for MAC (Table 1).

HBA – Horse blood agar.

MAC – MacConkey agar.

CHA – Chocolate agar.

NF – nuclear factor.

For the colonies from the HBA plate, the Gram staining test was conducted. It was found that Gram-positive cocci were presented in chains of three or four colonies or clusters similar to chains. The catalase test performed after the Gram test identified the enzyme catalase-positive bacterium. As a result, it was possible to speak about the presence of Staphylococci in the patient’s sputum sample. The coagulase test also presented a positive results, and the identified Staphylococcus was categorized as Staphylococcus aureus. This conclusion was also supported by the positive results of the DNase test because the clear zone and DNase +ve colonies were found (Table 2).

DNase – deoxyribonuclease.

The results of the Gram stain test allowed the development of the scheme for further microbiological investigation in order to confirm that the identified pathogen was of the Staphylococcus type (Figure 1).

The antibiotics sensitivity test indicated that the identified Staphylococcus aureus was resistant to penicillin, but it was susceptible to gentamicin, chloramphenicol, oxacillin, cefoxitin, and erythromycin (Table 3).

Sample Description: Sputum sample.

Notes: Purulent sputum sample, possible bronchitis.

Date: 23/4/2016.

Gram: Gram-positive cocci, chains of colonies.

Culture: Growth of Staphylococcus aureus.

Comments: Susceptible to gentamicin, chloramphenicol, oxacillin, cefoxitin, and erythromycin.

Bronchitis can be provoked by S. aureus, S. pneumonia, H. influenza, and M. catarrhalis among other bacteria. In 59-year-old patients, as well as elderly patients, the risks of developing complications associated with non-treated bronchitis increase, and it is important to identify the bacterium that causes the disease in the particular case (Kitara et al. 2011). Acute bronchitis is frequently caused by Staphylococcus aureus when the bacteria pass from the pharynx to bronchi, and the organism’s reaction to the bacteria is the inflammation with the production of mucus (Wiriyachaiporn et al. 2013). In order to identify whether bronchitis is caused by Staphylococcus aureus or other bacteria, it is necessary to examine the sputum sample and conduct a variety of tests.

In this case, the Gram stain test indicated that the bacteria were Gram-positive cocci that are typical of both Staphylococcus and Streptococcus, and they resembled both clusters and chains of colonies. Therefore, additional testing was necessary to distinguish between Staphylococcus and Streptococcus. The catalase test indicated that the bacteria are catalase – positive, and this condition is typical of Staphylococcus rather than Streptococcus. Moreover, this condition is characteristic of Staphylococcus aureus. In order to support the assumption about the morphology of the bacterium, it was necessary to conduct the coagulase and DNase tests. These tests allowed speaking about the bacteria as coagulase-positive. They contributed to creating clear zones. Therefore, the conclusion was that the male patient’s bronchitis was caused by Staphylococcus aureus.

In the 59-year-old patient, Staphylococcus aureus can also cause pneumonia; therefore, it was necessary to conduct the antibiotics sensitivity test in order to identify antibiotics that are most appropriate to be used in the patient’s case. Mishra and Bayer (2013) state that individual sensitivity can influence the effectiveness of using gentamicin, chloramphenicol, oxacillin, cefoxitin, and erythromycin in order to treat bronchitis in elderly patients. From this point, it is important to note that patients aged 59 years old and older are in the group of people who are usually affected by Staphylococcus aureus because of the lowered immunity (Kitara et al. 2011).

Public health considerations related to the treatment of persons with Staphylococcus aureus include the prescription of appropriate antibiotics. It is also important to focus on the isolation of patients during the period of treatment and the decrease of risks associated with the further possible infecting or spread of the untreated Staphylococcus aureus in the organism. Much attention should be paid to avoiding the auto-infection and monitoring the symptoms in the patient during the treatment.

Adegoke, A & Okoh, 2014, ‘Species diversity and antibiotic resistance properties of Staphylococcus of farm animal origin in Nkonkobe Municipality, South Africa’, Folia microbiologica , vol. 59, no. 2, pp. 133-140.

Cain, H 2014, Microbiological laboratory techniques manual , University of Melbourne, Melbourne.

Chatterjee, S, Ray, P, Aggarwal, A, Das, A & Sharma, M 2009, ‘A community-based study on nasal carriage of Staphylococcus aureus’, Indian Journal of Medical Research , vol. 130, no. 6, pp. 742-748.

Kaasch, A, Barlow, G, Edgeworth, J, Fowler, V & Hellmich, M 2014, Staphylococcus aureus bloodstream infection: a pooled analysis of five prospective, observational studies’, Journal of Infection , vol. 68, no. 3, pp. 242-251.

Kateete, D, Kimani, C, Katabazi, F & Okeng, 2010, ‘Identification of Staphylococcus aureus: DNase and Mannitol salt agar improve the efficiency of the tube coagulase test’, Annals of Clinical Microbiology and Antimicrobials , vol. 9, no. 1, 1-10.

Kitara, L, Anywar, A, Acullu, D, Odongo-Aginya, E & Aloyo, J 2011, ‘Antibiotic susceptibility of Staphylococcus aureus in suppurative lesions in Lacor Hospital, Uganda’, African Health Sciences , vol. 11, no. 3, pp. 34-39.

Mishra, N & Bayer, 2013, ‘Correlation of cell membrane lipid profiles with daptomycin resistance in methicillin-resistant Staphylococcus aureus’, Antimicrobial Agents and Chemotherapy , vol. 57, no. 2, pp. 1082-1085.

Pesavento, G, Ducci, B, Comodo, N & Nostro, 2010, ‘Antimicrobial resistance profile of Staphylococcus aureus isolated from raw meat: a research for methicillin-resistant Staphylococcus aureus (MRSA)’, Food Control , vol. 18, no. 3, pp. 196-200.

Shrestha, B, Pokhrel, B & Mohapatra, T 2009, ‘Phenotypic characterization of nosocomial isolates of Staphylococcus aureus with reference to MRSA’, The Journal of Infection in Developing Countries , vol. 3, no. 7, pp. 554-560.

Sudhanthiramani, S, Swetha, C & Bharathy, S 2015, ‘Prevalence of antibiotic-resistant Staphylococcus aureus from raw milk samples collected from the local vendors in the region of Tirupathi, India’, Veterinary World , vol. 8, no. 4, pp. 478-481.

Wiriyachaiporn, S, Howarth, P, Bruce, K & Dailey, L 2013, ‘Evaluation of a rapid lateral flow immunoassay for Staphylococcus aureus detection in respiratory samples’, Diagnostic Microbiology and Infectious Disease , vol. 75, no. 1, pp. 28-36.

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Bibliography

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22.2: Bacterial Infections of the Respiratory Tract

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Learning Objectives

• Identify the most common bacteria that can cause infections of the upper and lower respiratory tract
• Compare the major characteristics of specific bacterial diseases of the respiratory tract

The respiratory tract can be infected by a variety of bacteria, both gram positive and gram negative. Although the diseases that they cause may range from mild to severe, in most cases, the microbes remain localized within the respiratory system. Fortunately, most of these infections also respond well to antibiotic therapy.

Streptococcal Infections

A common upper respiratory infection, streptococcal pharyngitis (strep throat) is caused by Streptococcus pyogenes . This gram-positive bacterium appears as chains of cocci, as seen in Figure \(\PageIndex{1}\). Rebecca Lancefieldserologically classified streptococci in the 1930s using carbohydrate antigens from the bacterial cell walls. S. pyogenes is the sole member of the Lancefield group A streptococci and is often referred to as GAS, or group A strep.

Similar to streptococcal infections of the skin, the mucosal membranes of the pharynx are damaged by the release of a variety of exoenzymes and exotoxins by this extracellular pathogen. Many strains of S. pyogenes can degrade connective tissues by using hyaluronidase, collagenase and streptokinase. Streptokinase activates plasmin, which leads to degradation of fibrin and, in turn, dissolution of blood clots, which assists in the spread of the pathogen. Released toxins include streptolysins that can destroy red and white blood cells. The classic signs of streptococcal pharyngitis are a fever higher than 38 °C (100.4 °F); intense pharyngeal pain; erythema associated with pharyngeal inflammation; and swollen, dark-red palatine tonsils, often dotted with patches of pus; and petechiae (microcapillary hemorrhages) on the soft or hard palate (roof of the mouth) (Figure \(\PageIndex{2}\)). The submandibular lymph nodes beneath the angle of the jaw are also often swollen during strep throat.

Some strains of group A streptococci produce erythrogenic toxin. This exotoxin is encoded by a temperate bacteriophage (bacterial virus) and is an example of phage conversion (see The Viral Life Cycle ). The toxin attacks the plasma membranes of capillary endothelial cells and leads to scarlet fever (or scarlatina), a disseminated fine red rash on the skin, and strawberry tongue, a red rash on the tongue (Figure \(\PageIndex{2}\)). Severe cases may even lead to streptococcal toxic shock syndrome (STSS), which results from massive superantigen production that leads to septic shock and death.

S. pyogenes can be easily spread by direct contact or droplet transmission through coughing and sneezing. The disease can be diagnosed quickly using a rapid enzyme immunoassay for the group A antigen. However, due to a significant rate of false-negative results (up to 30% 1 ), culture identification is still the gold standard to confirm pharyngitis due to S. pyogenes . S. pyogenes can be identified as a catalase-negative, beta hemolytic bacterium that is susceptible to 0.04 units of bacitracin. Antibiotic resistance is limited for this bacterium, so most β-lactams remain effective; oral amoxicillin and intramuscular penicillin G are those most commonly prescribed.

Sequelae of S. pyogenes Infections

One reason strep throat infections are aggressively treated with antibiotics is because they can lead to serious sequelae, later clinical consequences of a primary infection. It is estimated that 1%–3% of untreated S. pyogenes infections can be followed by nonsuppurative (without the production of pus) sequelae that develop 1–3 weeks after the acute infection has resolved. Two such sequelae are acute rheumatic fever and acute glomerulonephritis.

Acute rheumatic fever can follow pharyngitis caused by specific rheumatogenic strains of S. pyogenes (strains 1, 3, 5, 6, and 18). Although the exact mechanism responsible for this sequela remains unclear, molecular mimicry between the M protein of rheumatogenic strains of S. pyogenes and heart tissue is thought to initiate the autoimmune attack. The most serious and lethal clinical manifestation of rheumatic fever is damage to and inflammation of the heart (carditis). Acute glomerulonephritis also results from an immune response to streptococcal antigens following pharyngitis and cutaneous infections. Acute glomerulonephritis develops within 6–10 days after pharyngitis, but can take up to 21 days after a cutaneous infection. Similar to acute rheumatic fever, there are strong associations between specific nephritogenic strains of S. pyogenes and acute glomerulonephritis, and evidence suggests a role for antigen mimicry and autoimmunity. However, the primary mechanism of acute glomerulonephritis appears to be the formation of immune complexes between S. pyogenes antigens and antibodies, and their deposition between endothelial cells of the glomeruli of kidney. Inflammatory response against the immune complexes leads to damage and inflammation of the glomeruli (glomerulonephritis).

Exercise \(\PageIndex{1}\)

• What are the symptoms of strep throat?
• What is erythrogenic toxin and what effect does it have?
• What are the causes of rheumatic fever and acute glomerulonephritis?

Acute Otitis Media

An infection of the middle ear is called acute otitis media (AOM), but often it is simply referred to as an earache. The condition is most common between ages 3 months and 3 years. In the United States, AOM is the second-leading cause of visits to pediatricians by children younger than age 5 years, and it is the leading indication for antibiotic prescription. 2

AOM is characterized by the formation and accumulation of pus in the middle ear. Unable to drain, the pus builds up, resulting in moderate to severe bulging of the tympanic membrane and otalgia (ear pain). Inflammation resulting from the infection leads to swelling of the eustachian tubes, and may also lead to fever, nausea, vomiting, and diarrhea, particularly in infants. Infants and toddlers who cannot yet speak may exhibit nonverbal signs suggesting AOM, such as holding, tugging, or rubbing of the ear, as well as uncharacteristic crying or distress in response to the pain.

AOM can be caused by a variety of bacteria. Among neonates, S. pneumoniae is the most common cause of AOM, but Escherichia coli , Enterococcus spp., and group B Streptococcus species can also be involved. In older infants and children younger than 14 years old, the most common bacterial causes are S. pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis . Among S. pneumoniae infections , encapsulated strains are frequent causes of AOM. By contrast, the strains of H. influenzae and M. cattarhalis that are responsible for AOM do not possess a capsule. Rather than direct tissue damage by these pathogens, bacterial components such as lipopolysaccharide (LPS) in gram-negative pathogens induce an inflammatory response that causes swelling, pus, and tissue damage within the middle ear (Figure \(\PageIndex{3}\)).

Any blockage of the eustachian tubes, with or without infection, can cause fluid to become trapped and accumulate in the middle ear. This is referred to as otitis media with effusion (OME). The accumulated fluid offers an excellent reservoir for microbial growth and, consequently, secondary bacterial infections often ensue. This can lead to recurring and chronic earaches, which are especially common in young children. The higher incidence in children can be attributed to many factors. Children have more upper respiratory infections, in general, and their eustachian tubes are also shorter and drain at a shallower angle. Young children also tend to spend more time lying down than adults, which facilitates drainage from the nasopharynx through the eustachian tube and into the middle ear. Bottle feeding while lying down enhances this risk because the sucking action on the bottle causes negative pressure to build up within the eustachian tube, promoting the movement of fluid and bacteria from the nasopharynx.

Diagnosis is typically made based on clinical signs and symptoms, without laboratory testing to determine the specific causative agent. Antibiotics are frequently prescribed for the treatment of AOM. High-dose amoxicillin is the first-line drug, but with increasing resistance concerns, macrolides and cephalosporins may also be used. The pneumococcal conjugate vaccine (PCV13) contains serotypes that are important causes of AOM, and vaccination has been shown to decrease the incidence of AOM. Vaccination against influenza has also been shown to decrease the risk for AOM, likely because viral infections like influenza predispose patients to secondary infections with S. pneumoniae . Although there is a conjugate vaccine available for the invasive serotype B of H. influenzae , this vaccine does not impact the incidence of H. influenzae AOM. Because unencapsulated strains of H. influenzae and M. catarrhalis are involved in AOM, vaccines against bacterial cellular factors other than capsules will need to be developed.

Bacterial Rhinosinusitis

The microbial community of the nasopharynx is extremely diverse and harbors many opportunistic pathogens, so it is perhaps not surprising that infections leading to rhinitis and sinusitis have many possible causes. These conditions often occur as secondary infections after a viral infection, which effectively compromises the immune defenses and allows the opportunistic bacteria to establish themselves. Bacterial sinusitis involves infection and inflammation within the paranasal sinuses. Because bacterial sinusitis rarely occurs without rhinitis, the preferred term is rhinosinusitis. The most common causes of bacterial rhinosinusitis are similar to those for AOM, including S. pneumoniae , H. influenzae , and M. catarrhalis .

Exercise \(\PageIndex{2}\)

• What are the usual causative agents of acute otitis media?
• What factors facilitate acute otitis media with effusion in young children?
• What factor often triggers bacterial rhinosinusitis?

The causative agent of diphtheria, Corynebacterium diphtheriae , is a club-shaped, gram-positive rod that belongs to the phylum Actinobacteria. Diphtheroids are common members of the normal nasopharyngeal microbiota. However, some strains of C. diphtheriae become pathogenic because of the presence of a temperate bacteriophage-encoded protein—the diphtheria toxin. Diphtheria is typically a respiratory infection of the oropharynx but can also cause impetigo-like lesions on the skin. Although the disease can affect people of all ages, it tends to be most severe in those younger than 5 years or older than 40 years. Like strep throat, diphtheria is commonly transmitted in the droplets and aerosols produced by coughing. After colonizing the throat, the bacterium remains in the oral cavity and begins producing the diphtheria toxin. This protein is an A-B toxin that blocks host-cell protein synthesis by inactivating elongation factor (EF)-2 (see Virulence Factors of Bacterial and Viral Pathogens ). The toxin’s action leads to the death of the host cells and an inflammatory response. An accumulation of grayish exudate consisting of dead host cells, pus, red blood cells, fibrin, and infectious bacteria results in the formation of a pseudomembrane. The pseudomembrane can cover mucous membranes of the nasal cavity, tonsils, pharynx, and larynx (Figure \(\PageIndex{4}\)). This is a classic sign of diphtheria. As the disease progresses, the pseudomembrane can enlarge to obstruct the fauces of the pharynx or trachea and can lead to suffocation and death. Sometimes, intubation, the placement of a breathing tube in the trachea, is required in advanced infections. If the diphtheria toxin spreads throughout the body, it can damage other tissues as well. This can include myocarditis (heart damage) and nerve damage that may impair breathing.

The presumptive diagnosis of diphtheria is primarily based on the clinical symptoms (i.e., the pseudomembrane) and vaccination history, and is typically confirmed by identifying bacterial cultures obtained from throat swabs. The diphtheria toxin itself can be directly detected in vitro using polymerase chain reaction (PCR)-based, direct detection systems for the diphtheria tox gene, and immunological techniques like radial immunodiffusion or Elek’s immunodiffusion test.

Broad-spectrum antibiotics like penicillin and erythromycin tend to effectively control C. diphtheriae infections. Regrettably, they have no effect against preformed toxins. If toxin production has already occurred in the patient, antitoxins (preformed antibodies against the toxin) are administered. Although this is effective in neutralizing the toxin, the antitoxins may lead to serum sickness because they are produced in horses (see Hypersensitivities ).

Widespread vaccination efforts have reduced the occurrence of diphtheria worldwide. There are currently four combination toxoid vaccines available that provide protection against diphtheria and other diseases: DTaP, Tdap, DT, and Td. In all cases, the letters “d,” “t,” and “p” stand for diphtheria, tetanus, and pertussis, respectively; the “a” stands for acellular. If capitalized, the letters indicate a full-strength dose; lowercase letters indicate reduced dosages. According to current recommendations, children should receive five doses of the DTaP vaccine in their youth and a Td booster every 10 years. Children with adverse reactions to the pertussis vaccine may be given the DT vaccine in place of the DTaP.

Exercise \(\PageIndex{3}\)

• What effect does diphtheria toxin have?
• What is the pseudomembrane composed of?

Bacterial Pneumonia

Pneumonia is a general term for infections of the lungs that lead to inflammation and accumulation of fluids and white blood cells in the alveoli. Pneumonia can be caused by bacteria, viruses, fungi, and other organisms, although the vast majority of pneumonias are bacterial in origin. Bacterial pneumonia is a prevalent, potentially serious infection; it caused more 50,000 deaths in the United States in 2014. 3 As the alveoli fill with fluids and white blood cells (consolidation), air exchange becomes impaired and patients experience respiratory distress (Figure \(\PageIndex{5}\)). In addition, pneumonia can lead to pleurisy, an infection of the pleural membrane surrounding the lungs, which can make breathing very painful. Although many different bacteria can cause pneumonia under the right circumstances, three bacterial species cause most clinical cases: Streptococcus pneumoniae , H . influenzae , and Mycoplasma pneumoniae . In addition to these, we will also examine some of the less common causes of pneumonia.

Pneumococcal Pneumonia

The most common cause of community-acquired bacterial pneumonia is Streptococcus pneumoniae . This gram-positive, alpha hemolytic streptococcus is commonly found as part of the normal microbiota of the human respiratory tract. The cells tend to be somewhat lancet-shaped and typically appear as pairs (Figure \(\PageIndex{6}\)). The pneumococci initially colonize the bronchioles of the lungs. Eventually, the infection spreads to the alveoli, where the microbe’s polysaccharide capsule interferes with phagocytic clearance. Other virulence factors include autolysins like Lyt A, which degrade the microbial cell wall, resulting in cell lysis and the release of cytoplasmic virulence factors. One of these factors, pneumolysin O, is important in disease progression; this pore-forming protein damages host cells, promotes bacterial adherence, and enhances pro-inflammatory cytokine production. The resulting inflammatory response causes the alveoli to fill with exudate rich in neutrophils and red blood cells. As a consequence, infected individuals develop a productive cough with bloody sputum.

Pneumococci can be presumptively identified by their distinctive gram-positive, lancet-shaped cell morphology and diplococcal arrangement. In blood agar cultures, the organism demonstrates alpha hemolytic colonies that are autolytic after 24 to 48 hours. In addition, S. pneumoniae is extremely sensitive to optochin and colonies are rapidly destroyed by the addition of 10% solution of sodium deoxycholate. All clinical pneumococcal isolates are serotyped using the quellung reaction with typing antisera produced by the CDC. Positive quellung reactions are considered definitive identification of pneumococci.

Antibiotics remain the mainstay treatment for pneumococci. β-Lactams like penicillin are the first-line drugs, but resistance to β-lactams is a growing problem. When β-lactam resistance is a concern, macrolides and fluoroquinolones may be prescribed. However, S. pneumoniae resistance to macrolides and fluoroquinolones is increasing as well, limiting the therapeutic options for some infections. There are currently two pneumococcal vaccines available: pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23). These are generally given to the most vulnerable populations of individuals: children younger than 2 years and adults older than 65 years.

Haemophilus Pneumonia

Encapsulated strains of Haemophilus influenzae are known for causing meningitis, but nonencapsulated strains are important causes of pneumonia. This small, gram-negative coccobacillus is found in the pharynx of the majority of healthy children; however, Haemophilus pneumonia is primarily seen in the elderly. Like other pathogens that cause pneumonia, H. influenzae is spread by droplets and aerosols produced by coughing. A fastidious organism, H. influenzae will only grow on media with available factor X (hemin) and factor V (NAD), like chocolate agar (Figure \(\PageIndex{7}\)). Serotyping must be performed to confirm identity of H. influenzae isolates.

Infections of the alveoli by H. influenzae result in inflammation and accumulation of fluids. Increasing resistance to β-lactams, macrolides, and tetracyclines presents challenges for the treatment of Haemophilus pneumonia. Resistance to the fluoroquinolones is rare among isolates of H. influenzae but has been observed. As discussed for AOM, a vaccine directed against nonencapsulated H. influenzae, if developed, would provide protection against pneumonia caused by this pathogen.

Tracy is a 6-year old who developed a serious cough that would not seem to go away. After 2 weeks, her parents became concerned and took her to the pediatrician, who suspected a case of bacterial pneumonia. Tests confirmed that the cause was Haemophilus influenzae . Fortunately, Tracy responded well to antibiotic treatment and eventually made a full recovery.

Because there had been several other cases of bacterial pneumonia at Tracy’s elementary school, local health officials urged parents to have their children screened. Of the children who were screened, it was discovered that greater than 50% carried H. influenzae in their nasal cavities, yet all but two of them were asymptomatic.

Why is it that some individuals become seriously ill from bacterial infections that seem to have little or no effect on others? The pathogenicity of an organism—its ability to cause host damage—is not solely a property of the microorganism. Rather, it is the product of a complex relationship between the microbe’s virulence factors and the immune defenses of the individual. Preexisting conditions and environmental factors such as exposure to secondhand smoke can make some individuals more susceptible to infection by producing conditions favorable to microbial growth or compromising the immune system. In addition, individuals may have genetically determined immune factors that protect them—or not—from particular strains of pathogens. The interactions between these host factors and the pathogenicity factors produced by the microorganism ultimately determine the outcome of the infection. A clearer understanding of these interactions may allow for better identification of at-risk individuals and prophylactic interventions in the future.

Mycoplasma Pneumonia (Walking Pneumonia)

Primary atypical pneumonia is caused by Mycoplasma pneumoniae . This bacterium is not part of the respiratory tract’s normal microbiota and can cause epidemic disease outbreaks. Also known as walking pneumonia, mycoplasma pneumonia infections are common in crowded environments like college campuses and military bases. It is spread by aerosols formed when coughing or sneezing. The disease is often mild, with a low fever and persistent cough. These bacteria, which do not have cell walls, use a specialized attachment organelle to bind to ciliated cells. In the process, epithelial cells are damaged and the proper function of the cilia is hindered (Figure \(\PageIndex{8}\)).

Mycoplasma grow very slowly when cultured. Therefore, penicillin and thallium acetate are added to agar to prevent the overgrowth by faster-growing potential contaminants. Since M. pneumoniae does not have a cell wall, it is resistant to these substances. Without a cell wall, the microbial cells appear pleomorphic. M. pneumoniae infections tend to be self-limiting but may also respond well to macrolide antibiotic therapy. β-lactams, which target cell wall synthesis, are not indicated for treatment of infections with this pathogen.

Chlamydial Pneumonias and Psittacosis

Chlamydial pneumonia can be caused by three different species of bacteria: Chlamydophila pneumoniae (formerly known as Chlamydia pneumoniae ), Chlamydophila psittaci (formerly known as Chlamydia psittaci ), and Chlamydia trachomatis . All three are obligate intracellular pathogens and cause mild to severe pneumonia and bronchitis. Of the three, Chlamydophila pneumoniae is the most common and is transmitted via respiratory droplets or aerosols. C. psittaci causes psittacosis, a zoonotic disease that primarily affects domesticated birds such as parakeets, turkeys, and ducks, but can be transmitted from birds to humans. Psittacosis is a relatively rare infection and is typically found in people who work with birds. Chlamydia trachomatis, the causative agent of the sexually transmitted disease chlamydia, can cause pneumonia in infants when the infection is passed from mother to baby during birth.

Diagnosis of chlamydia by culturing tends to be difficult and slow. Because they are intracellular pathogens, they require multiple passages through tissue culture. Recently, a variety of PCR- and serologically based tests have been developed to enable easier identification of these pathogens. Tetracycline and macrolide antibiotics are typically prescribed for treatment.

Health Care-Associated Pneumonia

A variety of opportunistic bacteria that do not typically cause respiratory disease in healthy individuals are common causes of health care-associated pneumonia. These include Klebsiella pneumoniae , Staphylococcus aureus , and proteobacteria such as species of Escherichia , Proteus , and Serratia . Patients at risk include the elderly, those who have other preexisting lung conditions, and those who are immunocompromised. In addition, patients receiving supportive therapies such as intubation, antibiotics, and immunomodulatory drugs may also be at risk because these interventions disrupt the mucociliary escalator and other pulmonary defenses. Invasive medical devices such as catheters, medical implants, and ventilators can also introduce opportunistic pneumonia-causing pathogens into the body. 4

Pneumonia caused by K. pneumoniae is characterized by lung necrosis and “currant jelly sputum,” so named because it consists of clumps of blood, mucus, and debris from the thick polysaccharide capsule produced by the bacterium. K. pneumoniae is often multidrug resistant. Aminoglycoside and cephalosporin are often prescribed but are not always effective. Klebsiella pneumonia is frequently fatal even when treated.

Pseudomonas Pneumonia

Pseudomonas aeruginosa is another opportunistic pathogen that can cause serious cases of bacterial pneumonia in patients with cystic fibrosis (CF) and hospitalized patients assisted with artificial ventilators. This bacterium is extremely antibiotic resistant and can produce a variety of exotoxins. Ventilator-associated pneumonia with P. aeruginosa is caused by contaminated equipment that causes the pathogen to be aspirated into the lungs. In patients with CF, a genetic defect in the cystic fibrosis transmembrane receptor (CFTR) leads to the accumulation of excess dried mucus in the lungs. This decreases the effectiveness of the defensins and inhibits the mucociliary escalator. P. aeruginosa is known to infect more than half of all patients with CF. It adapts to the conditions in the patient’s lungs and begins to produce alginate, a viscous exopolysaccharide that inhibits the mucociliary escalator. Lung damage from the chronic inflammatory response that ensues is the leading cause of mortality in patients with CF. 5

Exercise \(\PageIndex{4}\)

• What three pathogens are responsible for the most prevalent types of bacterial pneumonia?
• Which cause of pneumonia is most likely to affect young people?
• In what contexts does Pseudomonas aeruginosa cause pneumonia?

Clinical Focus: Part 2

John’s chest radiograph revealed an extensive consolidation in the right lung, and his sputum cultures revealed the presence of a gram-negative rod. His physician prescribed a course of the antibiotic clarithromycin. He also ordered the rapid influenza diagnostic tests (RIDTs) for type A and B influenza to rule out a possible underlying viral infection. Despite antibiotic therapy, John’s condition continued to deteriorate, so he was admitted to the hospital.

Exercise \(\PageIndex{5}\)

What are some possible causes of pneumonia that would not have responded to the prescribed antibiotic?

Tuberculosis

Tuberculosis (TB) is one of the deadliest infectious diseases in human history. Although tuberculosis infection rates in the United States are extremely low, the CDC estimates that about one-third of the world’s population is infected with Mycobacterium tuberculosis , the causal organism of TB, with 9.6 million new TB cases and 1.5 million deaths worldwide in 2014. 6

M. tuberculosis is an acid-fast, high G + C, gram-positive, nonspore-forming rod. Its cell wall is rich in waxy mycolic acids, which make the cells impervious to polar molecules. It also causes these organisms to grow slowly. M. tuberculosis causes a chronic granulomatous disease that can infect any area of the body, although it is typically associated with the lungs. M. tuberculosis is spread by inhalation of respiratory droplets or aerosols from an infected person. The infectious dose of M. tuberculosis is only 10 cells. 7

After inhalation, the bacteria enter the alveoli (Figure \(\PageIndex{9}\)). The cells are phagocytized by macrophages but can survive and multiply within these phagocytes because of the protection by the waxy mycolic acid in their cell walls. If not eliminated by macrophages, the infection can progress, causing an inflammatory response and an accumulation of neutrophils and macrophages in the area. Several weeks or months may pass before an immunological response is mounted by T cells and B cells. Eventually, the lesions in the alveoli become walled off, forming small round lesions called tubercles. Bacteria continue to be released into the center of the tubercles and the chronic immune response results in tissue damage and induction of apoptosis (programmed host-cell death) in a process called liquefaction. This creates a caseous center, or air pocket, where the aerobic M. tuberculosis can grow and multiply. Tubercles may eventually rupture and bacterial cells can invade pulmonary capillaries; from there, bacteria can spread through the bloodstream to other organs, a condition known as miliary tuberculosis. The rupture of tubercles also facilitates transmission of the bacteria to other individuals via droplet aerosols that exit the body in coughs. Because these droplets can be very small and stay aloft for a long time, special precautions are necessary when caring for patients with TB, such as the use of face masks and negative-pressure ventilation and filtering systems.

Eventually, most lesions heal to form calcified Ghon complexes. These structures are visible on chest radiographs and are a useful diagnostic feature. But even after the disease has apparently ended, viable bacteria remain sequestered in these locations. Release of these organisms at a later time can produce reactivation tuberculosis (or secondary TB). This is mainly observed in people with alcoholism, the elderly, or in otherwise immunocompromised individuals (Figure \(\PageIndex{9}\)).

Because TB is a chronic disease, chemotherapeutic treatments often continue for months or years. Multidrug resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains of M. tuberculosis are a growing clinical concern. These strains can arise due to misuse or mismanagement of antibiotic therapies. Therefore, it is imperative that proper multidrug protocols are used to treat these infections. Common antibiotics included in these mixtures are isoniazid, rifampin, ethambutol, and pyrazinamide.

A TB vaccine is available that is based on the so-called bacillus Calmette-Guérin (BCG) strain of M. bovis commonly found in cattle. In the United States, the BCG vaccine is only given to health-care workers and members of the military who are at risk of exposure to active cases of TB. It is used more broadly worldwide. Many individuals born in other countries have been vaccinated with BCG strain. BCG is used in many countries with a high prevalence of TB, to prevent childhood tuberculous meningitis and miliary disease.

The Mantoux tuberculin skin test (Figure \(\PageIndex{10}\)) is regularly used in the United States to screen for potential TB exposure (see Hypersensitivities ). However, prior vaccinations with the BCG vaccine can cause false-positive results. Chest radiographs to detect Ghon complex formation are required, therefore, to confirm exposure.

Exercise \(\PageIndex{6}\)

• What characteristic of Mycobacterium tuberculosis allows it to evade the immune response?
• What happens to cause miliary tuberculosis?
• Explain the limitations of the Mantoux tuberculin skin test.

Pertussis (Whooping Cough)

The causative agent of pertussis, commonly called whooping cough, is Bordetella pertussis , a gram-negative coccobacillus. The disease is characterized by mucus accumulation in the lungs that leads to a long period of severe coughing. Sometimes, following a bout of coughing, a sound resembling a “whoop” is produced as air is inhaled through the inflamed and restricted airway—hence the name whooping cough. Although adults can be infected, the symptoms of this disease are most pronounced in infants and children. Pertussis is highly communicable through droplet transmission, so the uncontrollable coughing produced is an efficient means of transmitting the disease in a susceptible population.

Following inhalation, B. pertussis specifically attaches to epithelial cells using an adhesin, filamentous hemagglutinin. The bacteria then grow at the site of infection and cause disease symptoms through the production of exotoxins. One of the main virulence factors of this organism is an A-B exotoxin called the pertussis toxin (PT). When PT enters the host cells, it increases the cyclic adenosine monophosphate (cAMP) levels and disrupts cellular signaling. PT is known to enhance inflammatory responses involving histamine and serotonin. In addition to PT, B. pertussis produces a tracheal cytotoxin that damages ciliated epithelial cells and results in accumulation of mucus in the lungs. The mucus can support the colonization and growth of other microbes and, as a consequence, secondary infections are common. Together, the effects of these factors produce the cough that characterizes this infection.

A pertussis infection can be divided into three distinct stages. The initial infection, termed the catarrhal stage, is relatively mild and unremarkable. The signs and symptoms may include nasal congestion, a runny nose, sneezing, and a low-grade fever. This, however, is the stage in which B. pertussis is most infectious. In the paroxysmal stage, mucus accumulation leads to uncontrollable coughing spasms that can last for several minutes and frequently induce vomiting. The paroxysmal stage can last for several weeks. A long convalescence stage follows the paroxysmal stage, during which time patients experience a chronic cough that can last for up to several months. In fact, the disease is sometimes called the 100-day cough.

In infants, coughing can be forceful enough to cause fractures to the ribs, and prolonged infections can lead to death. The CDC reported 20 pertussis-related deaths in 2012, 9 but that number had declined to five by 2015. 10

During the first 2 weeks of infection, laboratory diagnosis is best performed by culturing the organism directly from a nasopharyngeal (NP) specimen collected from the posterior nasopharynx. The NP specimen is streaked onto Bordet-Gengou medium. The specimens must be transported to the laboratory as quickly as possible, even if transport media are used. Transport times of longer than 24 hours reduce the viability of B. pertussis significantly.

Within the first month of infection, B. pertussis can be diagnosed using PCR techniques. During the later stages of infection, pertussis-specific antibodies can be immunologically detected using an enzyme-linked immunosorbent assay (ELISA).

Pertussis is generally a self-limiting disease. Antibiotic therapy with erythromycin or tetracycline is only effective at the very earliest stages of disease. Antibiotics given later in the infection, and prophylactically to uninfected individuals, reduce the rate of transmission. Active vaccination is a better approach to control this disease. The DPT vaccine was once in common use in the United States. In that vaccine, the P component consisted of killed whole-cell B. pertussis preparations. Because of some adverse effects, that preparation has now been superseded by the DTaP and Tdap vaccines. In both of these new vaccines, the “aP” component is a pertussis toxoid.

Widespread vaccination has greatly reduced the number of reported cases and prevented large epidemics of pertussis. Recently, however, pertussis has begun to reemerge as a childhood disease in some states because of declining vaccination rates and an increasing population of susceptible children.

Exercise \(\PageIndex{7}\)

• What accounts for the mucus production in a pertussis infection?
• What are the signs and symptoms associated with the three stages of pertussis?
• Why is pertussis becoming more common in the United States?

Legionnaires Disease

An atypical pneumonia called Legionnaires disease (also known as legionellosis) is caused by an aerobic gram-negative bacillus, Legionella pneumophila . This bacterium infects free-living amoebae that inhabit moist environments, and infections typically occur from human-made reservoirs such as air-conditioning cooling towers, humidifiers, misting systems, and fountains. Aerosols from these reservoirs can lead to infections of susceptible individuals, especially those suffering from chronic heart or lung disease or other conditions that weaken the immune system.

When L. pneumophila bacteria enter the alveoli, they are phagocytized by resident macrophages. However, L. pneumophila uses a secretion system to insert proteins in the endosomal membrane of the macrophage; these proteins prevent lysosomal fusion, allowing L. pneumophila to continue to proliferate within the phagosome. The resulting respiratory disease can range from mild to severe pneumonia, depending on the status of the host’s immune defenses. Although this disease primarily affects the lungs, it can also cause fever, nausea, vomiting, confusion, and other neurological effects.

Diagnosis of Legionnaires disease is somewhat complicated. L. pneumophila is a fastidious bacterium and is difficult to culture. In addition, since the bacterial cells are not efficiently stained with the Gram stain, other staining techniques, such as the Warthin-Starry silver-precipitate procedure, must be used to visualize this pathogen. A rapid diagnostic test has been developed that detects the presence of Legionella antigen in a patient’s urine; results take less than 1 hour, and the test has high selectivity and specificity (greater than 90%). Unfortunately, the test only works for one serotype of L. pneumophila (type 1, the serotype responsible for most infections). Consequently, isolation and identification of L. pneumophila from sputum remains the defining test for diagnosis.

Once diagnosed, Legionnaire disease can be effectively treated with fluoroquinolone and macrolide antibiotics. However, the disease is sometimes fatal; about 10% of patients die of complications. 11 There is currently no vaccine available.

Exercise \(\PageIndex{8}\)

• Why is Legionnaires disease associated with air-conditioning systems?
• How does Legionella pneumophila circumvent the immune system?

The zoonotic disease Q fever is caused by a rickettsia, Coxiella burnetii . The primary reservoirs for this bacterium are domesticated livestock such as cattle, sheep, and goats. The bacterium may be transmitted by ticks or through exposure to the urine, feces, milk, or amniotic fluid of an infected animal. In humans, the primary route of infection is through inhalation of contaminated farmyard aerosols. It is, therefore, largely an occupational disease of farmers. Humans are acutely sensitive to C. burnetii —the infective dose is estimated to be just a few cells. 12 In addition, the organism is hardy and can survive in a dry environment for an extended time. Symptoms associated with acute Q fever include high fever, headache, coughing, pneumonia, and general malaise. In a small number of patients (less than 5% 13 ), the condition may become chronic, often leading to endocarditis, which may be fatal.

Diagnosing rickettsial infection by cultivation in the laboratory is both difficult and hazardous because of the easy aerosolization of the bacteria, so PCR and ELISA are commonly used. Doxycycline is the first-line drug to treat acute Q fever. In chronic Q fever, doxycycline is often paired with hydroxychloroquine.

Bacterial Diseases of the Respiratory Tract

Numerous pathogens can cause infections of the respiratory tract. Many of these infections produce similar signs and symptoms, but appropriate treatment depends on accurate diagnosis through laboratory testing. The tables in Figure \(\PageIndex{11}\) and Figure \(\PageIndex{12}\) summarize the most important bacterial respiratory infections, with the latter focusing specifically on forms of bacterial pneumonia.

Key Concepts and Summary

• A wide variety of bacteria can cause respiratory diseases; most are treatable with antibiotics or preventable with vaccines.
• Streptococcus pyogenes causes strep throat , an infection of the pharynx that also causes high fever and can lead to scarlet fever , acute rheumatic fever , and acute glomerulonephritis .
• Acute otitis media is an infection of the middle ear that may be caused by several bacteria, including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis . The infection can block the eustachian tubes, leading to otitis media with effusion .
• Diphtheria , caused by Corynebacterium diphtheriae , is now a rare disease because of widespread vaccination. The bacteria produce exotoxins that kill cells in the pharynx, leading to the formation of a pseudomembrane ; and damage other parts of the body.
• Bacterial pneumonia results from infections that cause inflammation and fluid accumulation in the alveoli. It is most commonly caused by S. pneumoniae or H. influenzae . The former is commonly multidrug resistant.
• Mycoplasma pneumonia results from infection by Mycoplasma pneumoniae ; it can spread quickly, but the disease is mild and self-limiting.
• Chlamydial pneumonia can be caused by three pathogens that are obligate intracellular parasites. Chlamydophila pneumoniae is typically transmitted from an infected person, whereas C. psittaci is typically transmitted from an infected bird. Chlamydia trachomatis , may cause pneumonia in infants.
• Several other bacteria can cause pneumonia in immunocompromised individuals and those with cystic fibrosis.
• Tuberculosis is caused by Mycobacterium tuberculosis . Infection leads to the production of protective tubercles in the alveoli and calcified Ghon complexes that can harbor the bacteria for a long time. Antibiotic-resistant forms are common and treatment is typically long term.
• Pertussis is caused by Bordetella pertussis . Mucus accumulation in the lungs leads to prolonged severe coughing episodes (whooping cough) that facilitate transmission. Despite an available vaccine, outbreaks are still common.
• Legionnaires disease is caused by infection from environmental reservoirs of the Legionella pneumophila bacterium. The bacterium is endocytic within macrophages and infection can lead to pneumonia, particularly among immunocompromised individuals.
• Q fever is caused by Coxiella burnetii , whose primary hosts are domesticated mammals (zoonotic disease). It causes pneumonia primarily in farm workers and can lead to serious complications, such as endocarditis.
• 1 WL Lean et al. “Rapid Diagnostic Tests for Group A Streptococcal Pharyngitis: A Meta-Analysis.” Pediatrics 134, no. 4 (2014):771–781.
• 2 G. Worrall. “Acute Otitis Media.” Canadian Family Physician 53 no. 12 (2007):2147–2148.
• 3 KD Kochanek et al. “Deaths: Final Data for 2014.” National Vital Statistics Reports 65 no 4 (2016).
• 4 SM Koenig et al. “Ventilator-Associated Pneumonia: Diagnosis, Treatment, and Prevention.” Clinical Microbiology Reviews 19 no. 4 (2006):637–657.
• 5 R. Sordé et al. “Management of Refractory Pseudomonas aeruginosa Infection in Cystic Fibrosis.” Infection and Drug Resistance 4 (2011):31–41.
• 6 Centers for Disease Control and Prevention. “Tuberculosis (TB). Data and Statistics.” http://www.cdc.gov/tb/statistics/default.htm
• 7 D. Saini et al. “Ultra-Low Dose of Mycobacterium tuberculosis Aerosol Creates Partial Infection in Mice.” Tuberculosis 92 no. 2 (2012):160–165.
• 8 G. Kaplan et al. “ Mycobacterium tuberculosis Growth at the Cavity Surface: A Microenvironment with Failed Immunity.” Infection and Immunity 71 no.12 (2003):7099–7108.
• 9 Centers for Disease Control and Prevention. “2012 Final Pertussis Surveillance Report.” 2015. http://www.cdc.gov/pertussis/downloa...eport-2012.pdf . Accessed July 6, 2016.
• 10 Centers for Disease Control and Prevention. “2015 Provisional Pertussis Surveillance Report.” 2016. http://www.cdc.gov/pertussis/downloa...rovisional.pdf . Accessed July 6, 2016.
• 11 Centers for Disease Control and Prevention. “ Legionella (Legionnaires’ Disease and Pontiac Fever: Diagnosis, Treatment, and Complications).” http://www.cdc.gov/legionella/about/diagnosis.html . Accessed Sept 14, 2016.
• 12 WD Tigertt et al. “Airborne Q Fever.” Bacteriological Reviews 25 no. 3 (1961):285–293.
• 13 Centers for Disease Control and Prevention. “Q fever. Symptoms, Diagnosis, and Treatment.” 2013. http://www.cdc.gov/qfever/symptoms/index.html . Accessed July 6, 2016.

Home Essay Examples Health Respiratory System

Analysis Of Respiratory Tract Infections

• Category Health
• Subcategory Human Body
• Topic Respiratory System

The respiratory tract is a general term that is utilized to depict all the body parts that are associated with helping an individual to breathe; the air is inhaled into the lungs due to muscle contraction so as to give oxygen to body tissues and is exhaled afterward due to muscle relaxation to expel the waste product carbon dioxide. The respiratory tract is subdivided into: the upper respiratory tract, which incorporates the nose and nasal cavity; the paranasal sinuses, which are air-filled cavities found within the cheekbones and forehead; the mouth, including the tonsils; the pharynx, which is at the rear of the throat to forestall foreign articles, such as food, from dropping down into the lungs; and the larynx or ‘voice box,’ which is the portion of the throat that contains the vocal cords, making up the throat; and the lower respiratory tract, which incorporates the trachea or “windpipe,” which is the tube that attaches the throat to the lungs; the bronchi, which are the two branches that the trachea divides into as it enters the lungs; the bronchioles, which are air passages found throughout the lungs that branch off like tree limbs from the bronchi; and the alveoli, which are tiny air sacs found at the end of the bronchioles, all of which make up the lungs.

Respiratory tract infections (RTIs) are any transmissible diseases concerning the respiratory tract. They are normally recurrent as the respiratory tract is significantly more vulnerable to disease than any other part of the body basically in light of the fact that microorganisms can easily access the tract during inhalation through the nose or mouth; nevertheless, RTIs are especially more frequent in fall and winter seasons, when school begins and indoor overcrowding encourages transmission. As the respiratory tract is subdivided into the upper respiratory tract and the lower respiratory tract, RTIs are likewise subdivided into upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs). URTIs consist of common cold, sinusitis, pharyngitis, epiglottitis, and laryngotracheitis; which are generally non-malignant, temporary and self-limited, despite the fact that epiglottitis and laryngotracheitis can be serious in pediatrics. Etiologic agents playing a role in URTIs include viruses, bacteria, mycoplasma, and fungi. LRTIs consist of bronchitis, bronchiolitis, and pneumonia; these diseases, particularly pneumonia, can be critical or lethal. Even though viruses, mycoplasma, rickettsia, and fungi would all be able to cause LRTIs, bacteria are the prevailing pathogens; responsible for a much higher rate of lower than of upper respiratory tract infections.

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Common cold, from its name, is the most common among all respiratory infections and is the principal motive of patient visits to the doctor, along with work and school absenteeism. Most colds are brought about by viruses; Rhinoviruses with more than 100 serotypes are the most typical pathogens, causing no less than 25% of cold cases in grown-ups, while Coronaviruses might be accountable for over 10% of the cases. Respiratory syncytial viruses, Parainfluenza viruses, influenza viruses, and adenoviruses have all been found to be connected to common cold as well; all the above-mentioned agents show seasonal variations in occurrence. The cause of 30% to 40% of cold cases, however, has not been determined yet. The viruses seem to act through the direct intrusion of epithelial cells of the respiratory mucosa, yet whether there is definite demolition and sloughing of these cells or loss of ciliary activity relies upon the particular virus involved. There is a rise in both leukocyte infiltration and nasal secretions, as well as a large sum of protein and immunoglobulin, proposing that cytokines and immune mechanisms might be the reason behind a portion of the symptoms of the common cold.

After an incubation span of 2 to 3 days, standard manifestations of nasal discharge and obstruction, sneezing, cough, and sore throat occur in both children and adults, along with myalgia and headache; however, fever is uncommon. The extent of the symptoms and viral shedding depends on the pathogen and the patient’s age. Complications are normally uncommon, yet sinusitis and otitis media may follow. The diagnosis of a common cold is normally based on the indications; the absence of fever joined with manifestations of localization to the nasopharynx. In contrast to allergic rhinitis, eosinophils are missing in nasal secretions; although it is conceivable to seclude the viruses for a conclusive diagnosis, that is seldom authorized. Treatment of the common cold is usually symptomatic; antipyretics, decongestants, fluids, and bed rest typically do the trick. Limitation of mingling to abstain from infecting others, alongside good sanitization, are the best measures to inhibit the spread of the malady as no vaccine is commercially obtainable for cold prophylaxis.

Sinusitis is an acute inflammatory condition of at least one of the paranasal sinuses. Infection represents a significant part of this illness; sinusitis frequently develops from infections of other positions of the respiratory tract since the paranasal sinuses are adjacent to, and connect with, the upper respiratory tract. Acute sinusitis typically follows a common cold, which is for the most part of viral etiology; however, vasomotor and allergic rhinitis may likewise be precursors to the origination of sinusitis. Blockage of the sinus ostia because of the presence of foreign bodies, deviation of the nasal septum, polyps, or tumors can lead to sinusitis as well. Infection of the maxillary sinuses may happen after dental extractions or the expansion of infection from the roots of the upper teeth. The most well-known bacterial agents accountable for acute sinusitis are Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis; moreover, additional agents including Staphylococcus aureus, Streptococcus pyogenes, gram-negative bacteria, and anaerobes have further been retrieved as chronic sinusitis is usually an assorted infection of aerobic and anaerobic organisms. 

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• Research article
• Open access
• Published: 25 October 2019

Risk factors of acute respiratory infections among under five children attending public hospitals in southern Tigray, Ethiopia, 2016/2017

• Sielu Alemayehu   ORCID: orcid.org/0000-0001-5072-6465 1 ,
• Kalayou Kidanu 1 ,
• Tensay Kahsay 1 &
• Mekuria Kassa 1  

BMC Pediatrics volume  19 , Article number:  380 ( 2019 ) Cite this article

8301 Accesses

20 Citations

Metrics details

Acute Respiratory infection accounts for 94,037000 disability adjusted life years and 1.9 million deaths worldwide. Acute respiratory infections is the most common causes of under-five illness and mortality. The under five children gets three to six episodes of acute respiratory infections annually regardless of where they live. Disease burden due to acute respiratory infection is 10–50 times higher in developing countries when compared to developed countries. The aim of this study was to assess risk factors of acute respiratory infection among under-five children attending Public hospitals in Southern Tigray, Ethiopia 2016/2017.

Institution based case control study was conducted from Nov 2016 to June 2017. Interviewer administered structured questionnaire was used to collect data from a sample of 288 (96 cases and 192 controls) children under 5 years of age. Systematic random sampling was used to recruit study subjects and SPSS version 20 was used to analyze the data. Bivariate and multivariate analysis were employed to examine statistical association between the outcome variable and selected independent variables at 95% confidence level. Level of statistical Significance was declared at p  < 0.05. Tables, figures and texts were used to present data.

One hundred sixty (55.6%) and 128 (44.4%) of the participants were males and females respectively. Malnutrition (AOR = 2.89; 95%CI: 1.584–8.951; p  = 0.039), cow dung use (AOR =2.21; 95%CI: 1.121–9.373; p  = 0.014), presence of smoker in the family (AOR = 0.638; 95% CI: 0.046–0.980; p  = 0.042) and maternal literacy (AOR = 3.098; 95%CI: 1.387–18.729; p  = 0.021) were found to be significant predictors of acute respiratory infection among under five children.

According to this study maternal literacy, smoking, cow dung use and nutritional status were strongly associated with increased risk of childhood acute respiratory infection. Health care providers should work jointly with the general public, so that scientific knowledge and guidelines for adopting particular preventive measures for acute respiratory infection are disseminated.

Peer Review reports

Acute Respiratory infection (ARI) accounts for an average 94,037000 disability adjusted life years (DALY) and 1.9 million mortalities throughout the world. The disease is among the most common causes of both illness and mortality in children aged below 5 years [ 1 , 2 ]. Acute respiratory infection contributes 2 to 4% of deaths in children less than 5 years of age in developed countries. These causes contribute 19 to 21% of child death in the eastern Mediterranean, Africa and South East Asia regions [ 3 ]. Although the frequency of ARI is similar in both the developed and developing countries, mortality due to ARI is 10–50 times higher in developing countries [ 4 ].

In countries with high pediatric population, one fourth of all pediatric hospital admissions are mainly due to ARI. Each year, 3% of all children less than 12 months of age need to be admitted for moderate or severe lower respiratory tract infections [ 5 ].

Ethiopia has made investments to reduce the morbidly and mortality of ARI. Integrated management of common childhood illness and community case management are among the programme initiatives scaled up nationally to address ARI in the country [ 6 ].

There are many socio-cultural, demographic and environmental risk factors that predispose children less than 5 years to acquire Respiratory Tract Infections (RTIs). Even though many of these risk factors are preventable [ 7 ], they have not been documented in many regions in Ethiopia making it difficult to develop algorithms for the management of this group of patients.

Considering the feasibility of the study design and the dynamic nature of the pediatric population a case control study design was employed aimed at determining the associated risk factors of ARI amongst children under 5 years of age who attend the southern Tigray Public Hospitals.

Study design

Since the pediatric population is a dynamic population and difficult to follow-up, an institutional based unmatched case control study design was employed to collect data on under five children’s risk factors of acute respiratory infection.

Source population and study population

The source population was all children less than 5 years of age in Southern zone of Tigray coming to public Hospitals. The study population was all sampled children of less than 5 years of age attending in the five public Hospitals during the data collection period.

Eligibility criteria

Children of under 5 years of age who diagnosed with ARI at time of data collection period in which their mothers accept to provide informed consent for their children. Exclusion criteria were children whose mothers or care takers were refused to participate in the study.

Selection of cases

The data collectors identified children who were diagnosed with ARI by the physician in the outpatient clinic. The data collectors then selected the study subjects by systematic random sampling method (an interval of 2 was used to get the actual study participants). Following this selection, after spoken informed consent was given participants were included in the study.

Selection of controls

The study data collectors selected the controls on meeting the definition of controls. The recruitment of the controls was done as for the cases as outlined in the above procedure.

Study variables

Dependent variable was acute respiratory infection. Independent variables were, Parental Social Demographic factors, Child Physiological/nutritional factors and Environmental characteristics.

Conceptual framework

The conceptual frame work of this study illustrates acute respiratory infection and its risk factors. As depicted in Fig.  1 , conceptual framework is developed for this research after reviewing the relevant literatures (Fig. 1 ).

conceptual framework to assess risk factors of acute respiratory infection among under-five children

Sample size determination

Sample size was calculated using Epi Info 7.0 StatCalc program by taking assumptions of 95% confidence level, two controls for each case, 80% power and 18.3% controls having wasting syndrome giving OR of 2.42 [ 8 ], Giving a total sample of 261 (87 cases and 174 controls). Adding 10% non-response rate the final sample was found to be 288 (96 cases and 192 controls). Wasting is selected because it was the exposure variable that gave the highest sample size for cases and controls among the other variables in a study conducted in Kenya [ 8 ].

Sampling procedure

All the five public hospitals in the zone were included in the study. As a marker for proportional sample size allocation for the hospitals, client flow of three consecutive previous months prior to the data collection period was observed. Systematic random sampling was used to recruit study subjects (Fig.  2 ).

schematic presentation of sampling procedure of a research project

Data collection tools

Interviewer administered structured questionnaire was used to collect data on risk factors of acute respiratory infection among under five children attending the five public hospitals. The questionnaire was adopted from previous studies and modified accordingly; it was first developed in English and translated in to the local Tigrigna language, and was then translated back to English to check the consistency. The data collection tool is included as an Additional file  1 .

Data collection process

Seven individuals who have completed their BSc in nursing from a recognized University were recruited (five of them for data collection and two of them for supervision) and each hospital’s chief executive officer met and asked for permission. The data collection was held for a total of 8 months from November 2016 - June/2017.

Operational definition

Acute Respiratory Infections (ARI) in children: children with any one or combination of symptoms and signs like cough, sore throat, rapid breathing, noisy breathing, chest in drawing, at any time in the last 2 weeks.

Children less than 5 years of age diagnosed with ARI in the hospitals and those referred from other health facilities with the diagnosis of ARI.

Children who visit the hospitals for diagnosis other than ARI.

Refers to low weight-for-height where a child is thin for his/her height but not necessarily short.

Data quality control and assurance management

The data collectors were trained for 1 day and the supervisors were visiting the data collectors once a day to check if they collect the data appropriately. Pretest was carried out on 10% of the sample in two health centers of the zone which were not included in the actual data collection 2 weeks before the actual data collection and the questions were revised based on the response obtained so that questions that create ambiguity were rephrased.

Data analysis procedure

The data was first recorded and cleaned then analyzed using SPSS version 20 software statistical packages. Missing values were treated by SPSS too. Frequency and proportions were used to describe the study population in relation to relevant variables. Binary logistic regression was computed to assess statistical association via Odds ratio, and significance of statistical association was assured or tested using 95% confidence interval and P -value (0.05). Bivariate and multivariate analysis was employed to examine the relationship or statistical association between the outcome variable and selected independent variables. Variables which were significant at p  < 0.05 in the bivariate analysis were taken to multivariate analysis to control the possible confounders. Results were presented using tables, figures and texts.

Ethical consideration

Ethical clearance was secured from Mekelle University College of health science IRB (research committee).

Socio demographic characteristics of the respondents

A total of 288 (96 cases and 192 controls) under five children were included in the study with a response rate of 100%. The children were aged between 4 and 59 months with median age of 16.5 months (Mean ± SD; 20.8 ± 13.9).

Fifty seven (62%) of the cases and 100 (51%) of the controls were rural dwellers. About three fourth of the respondents 227(78.8%) were Orthodox in religion. Thirty six (39.1%) of the mothers of cases and 48(24.5%) of mothers of controls were illiterate with only 4(2%) of mothers of controls completed college program. Fifty two (56.5%) of the cases and 108(55.1%) of the controls were males (Table  1 ).

Factors associated with acute respiratory infection

Child and parent related factors.

Among variables under this category maternal literacy, maternal occupation and household family size demonstrate significant association with acute respiratory infection of under five children at the bivariate analysis.

Most of the respondents were illiterate with 36 (39.1%) of caretakers of cases being unable to read and write and 59(30%) caretakers of controls having at least secondary education. A significant association was found between maternal literacy and risk of ARI by bivariate analysis (COR = 2.95, 95% CI: 1.446–6.017; p  = 0.04).

As shown in Table  1 , over 50% of the homes had between 5 and 7 persons living in the house. A significant association was found between family size and risk of ARI by bivariate analysis (OR = 0.237 (0.101–0.555, p  = 0.02) (Table  1 ).

Number of siblings, birth order and nutritional status were found to show significant association with under five children acute respiratory infection in the bivariate analysis.

The highest proportion of children had 3 and above siblings, among them were 54 (58.7%) cases and 84 (42.9%) control children. Number of siblings were found to be significantly associated with ARI ( p  = 0.041). Birth order of the child were found to be significantly associated with risk of ARI ( p  = 0.048).

Overall, malnutrition (severe and moderate; MUAC< 12.5 mm) was found significantly associated with increased risk of ARI (COR = 1.51, 95% CI: 1.779–9.296; p  = 0.001) in the bivariate analysis (Table  1 ).

Environmental factors

Among variables of this category cow dung use and presence of smoker in the house illustrate significant association with acute respiratory infection of under five children in the bivariate analysis.

Among the fuel types used cow dung for cooking was found to be associated with Acute respiratory infection on bivariate analysis ( p  = 0.002). A significant association was found between smoking and risk of ARI by Bivariate analysis (OR = 0.139, 95% CI: 0.043–0.444) (Table  2 ).

Overall factors of acute respiratory infection in children

In the bi-variable logistic regression analysis, variables such as maternal literacy, maternal occupation, family size, birth order, number of siblings, presence of smoker in the house, cow dung use and wasting were appeared to be associated with acute respiratory infection. Those variables which were significant in bivariate analysis at p  < 0.05 were taken to multivariate analysis to control the possible confounders. Then on multivariate analysis only maternal literacy, cow dung use and nutritional status were found to be associated with ARI.

Children from houses which used cow dung for their fuel were 2 times (AOR =2.21; 95%CI: 1.121–9.373; p  = 0.014) more likely to develop ARI. Similarly, ARI was about 3 times (AOR = 2.89; 95%CI: 1.584–8.951; p  = 0.039) more common among under five children who were wasted (Table  3 ).

This study found a significant association of malnutrition with ARI. The result contrasts to a case control study conducted in Kenya which reports an inverse relationship between ARI and wasting (OR = 2.42) [ 8 ]. Findings of this study also compared with case control study conducted in Zimbabwe which reported that current and past malnutrition were associated with ARI in children under five with OR = 2.67 [ 9 ]. Earlier study conducted in Riyadh city also reported that ARI was more seen in undernourished children (22.2%vs 15.8%; p  = 0.001) with increased incidence of ARI due to weakening nutritional status ( P  = 0.05) [ 8 ]. Declining MUAC ( p  = 0.001) was reported to be associated with ARI and in the nonappearance of other factors malnutrition alone significantly affect the ARI in under 2 years children [ 10 ]. One possible explanation for this contrasting finding might be that the effect of lessened cellular immunity in undernourished children which makes them more disposed to ARI. Acute Respiratory Infections usually occur more often, last longer, and are starker in malnourished children, classically because the mucous membranes and other mechanical structures designed to keep the respiratory tract clear are impaired, and the immune system has not developed properly [ 11 ].

This study also found a noteworthy association of maternal literacy with ARI but not with father’s literacy. Parker RL [ 12 ], revealed risk of ARI declined with education of parents. This might be because usually father remains outside for job most of the times but mother is always in the home taking care of children and household activities. Mother due to her close connotation with child knows the minor variations in child’s health than father. Due to such factors mother’s educational status might play important role in child’s disease than father’s literacy.

Cow dung use was the other variable found to be associated with ARI in this study. This result is in agreement with study done by Vinod Mishra et al. [ 12 ], who revealed an association of cow dung use with ARI (OR = 2.2). This could be because of the high daily concentrations of pollutants found in such settings and the large amount of time young children spend with their mothers doing household cooking.

Limitations of the study

Diagnosis of ARI was based on clinical WHO IMNCI classification guideline, which could introduce misclassification bias which could lead to selection bias.

Being institution based case control the study may have limitation in the generalizability of the findings.

Also, this study selectively addressed certain factors of under-five ARI while various factors are found to cause the diseases

This study revealed that, maternal literacy, cow dung use, and nutritional status were strongly associated with increased risk of childhood ARI.

Based on the findings in this study, the following are recommended.

Each Wereda’s Health Office of the zone, in teamwork with the health services in the wereda, ought prepare plans to implement community-based interventions focused towards better food, supplementation (vitamin supplements or fortified milk) to have significant optimistic benefits in dropping malnutrition

Health care providers in partnership with other participants should have plan to provide health education and choices of cooking other than cow dung.

Investigators should conduct extra studies related to this problematic in the area so that all the likely factors could be explored

The FMOH should give weight to mark the mothers familiar concerning their health and kids’ health as when design to control childhood diseases

Generally, it is suggested that the policy makers and academicians/health care providers should effort together to make a communication stage with the general community, through which scientific knowledge and guidelines for adopting particular preventive measures for ARI are disseminated. Since community responses to the ARI epidemic are dynamic, continual surveillance of community responses is valuable and would facilitate relevant governmental risk communication and health education efforts.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Acquired Immune Deficiency Syndrome

Adjusted Odds Ratio

Acute respiratory infection

Confidence interval

Crude Odds Ratio

Disability adjusted life years

Global Buren of Disease

Integrated Management of childhood Illness

Lower respiratory tract infection

Ministry Of Health

Primary Health Care

Respiratory Synctial Virus

Severe Acute Respiratory Infections

United Nations Children’s Fund

Upper Respiratory Tract Infection

United States of America

World Health Organization

WHO. Acute Respiratory infections in children: case management in small hospitals in developing countries a manual for doctors and other senior health workers (WHO/ARI/905). Geneva: WHO; 1990.

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van Woensel JBM, Viral lower respiratory tract infection in infants and young children. BMJ. 2003;327:36–40.

Miller NP, Amouzou A, Tafesse M, Hazel E, Legesse H, Degefie T, Victora CG, Black RE, Bryce J. Integrated community case management of childhood illness in Ethiopia: implementation strength and quality of care. Am J Trop Med Hyg. 2014;13:751.

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Matu MN. Risk factors and cost of illness for acute respiratory infections in children under five years of age attending selected health facilities in Nakuru County, Kenya: Jomo Kenyatta University of Agriculture and Technology; 2015. http://hdl.handle.net/123456789/1590 .

Mishra V, et al. lndoor air pollution from biomass combustion and acute respiratory illness in preschool age children in Zimbabwe. Int J Epidemiol. 2003;32(5):847–53.

Cunha AL. Relationship between acute respiratory infection and malnutrition in children under 5 years of age. Acta Pediatr. 2000;89:608–9.

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Parker RL. Acute respiratory illness in children: PHC responses. Health Policy Plan. 1987;2:279–88.

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Acknowledgements

I am indebted to extend my earnest thanks to Mr. Kalayou Kidanu and Mr. Tensay Kahsay, my advisors, for their enriching and critical comments and suggestions for the preparation of this thesis. I am also very grateful to Southern Tigray public hospitals which largely helped the realization of the study through providing relevant information related to the study.

Finally, my deepest thanks shall goes to the study participants, data collectors and supervisors who took part in the study only earnestly without whom the study would have largely been impossible.

This thesis work is made possible by the support of the American people through the Mekelle University under Agreement No. AID-663-A-11-00017. The contents of this document are the sole responsibility of the author and do not necessarily reflect the views of Mekelle University.

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Contributions

SA: Collected the data and involved in the analysis. KK: Designed the study, analysis and interpretation of data. TK: participated in the sequence alignment, coordination. MK: Involved in the drafts and critical revision of the manuscript. N.B. All authors read and approved the final version of the manuscript.

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Correspondence to Sielu Alemayehu .

Ethics declarations

Ethics approval and consent to participate.

Ethical clearance was secured from Mekelle University College of health science IRB (research committee). Official letter of permissions was obtained from Tigray Regional Health Bureau and submitted to respective public hospitals’ CEO office and respondents were informed in detail about the purpose of the study. Information was then collected after written consent was obtained from each participant (guardians/parents of the children with ARI). Respondents were allowed to refuse or discontinue participation at any time they want. Information was collected anonymously and confidentiality was assured throughout the study period.

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Additional file 1:.

Questionnaire to assess risk factors of acute respiratory tract infections among under five children attending public hospitals in southern Tigray, Ethiopia.

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Alemayehu, S., Kidanu, K., Kahsay, T. et al. Risk factors of acute respiratory infections among under five children attending public hospitals in southern Tigray, Ethiopia, 2016/2017. BMC Pediatr 19 , 380 (2019). https://doi.org/10.1186/s12887-019-1767-1

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Received : 25 February 2019

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Published : 25 October 2019

DOI : https://doi.org/10.1186/s12887-019-1767-1

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Respiratory Infections

Respiratory tract infections (RTIs) are a common health problem of international travelers. Travelers may be at increased risk of RTIs due to travel itself (mingling and close quarters in airports, airplanes, cruise ships, and hotels), and due to unique exposure at travel destinations. The clinical spectrum of RTIs in travelers is broad and includes upper RTIs, pharyngitis, otitis, laryngitis, bronchitis, and pneumonia. Most travelers who acquire an RTI only develop mild disease, and only a minority seek medical attention. All travelers should be up to date on any indicated vaccines based on age and medical condition that prevent RTIs, including influenza, measles, pneumococcal diseases, Haemophilus influenzae b, Neisseria meningitidis , diphtheria, and pertussis.

• • Respiratory tract infections (RTIs) are among the most common illnesses reported by travelers. Most RTIs are viral, involve the upper respiratory tract, and do not require specific diagnosis or treatment.
• • Influenza is often considered the most important travel-related infection. Travelers play an integral role in the yearly and global spread of influenza.
• • Lower RTIs, including pneumonia, often require antimicrobial therapy.
• • High-risk groups such as infants, small children, the elderly, and subjects with chronic tracheobronchial or pulmonary disease are at increased risk of developing severe clinical consequences should infection occur. All international travelers should be immunized for seasonal influenza unless otherwise contraindicated, and travelers should be instructed in hand hygiene and sneeze and cough hygiene.
• • All travelers should be up to date on any indicated vaccines that prevent RTIs, including measles, pneumococcal diseases, Haemophilus influenzae b (Hib), meningococcal disease, diphtheria, and pertussis.
• • Travelers may be at increased risk of geographically restricted RTIs, and clinicians should be familiar with the major manifestations of these illnesses.

Introduction

Respiratory diseases are a frequent 1 , 2 , 3 and potentially life-threatening health problem in travelers. Travelers may be at increased risk of certain respiratory tract infections (RTIs) due to travel itself (mingling and close quarters in airports, airplanes, cruise ships, and hotels; and risk of influenza, legionellosis, and tuberculosis [TB]) and due to unique exposure at travel destinations (melioidosis, plague, Q fever, coccidioidomycosis, and histoplasmosis). Travel-related respiratory infections can lead to importation and secondary transmission, as occurred during the severe acute respiratory syndrome (SARS) outbreak in 2003, and more recently with Middle East respiratory syndrome coronavirus (MERS-CoV) and H1N1 influenza. 4 This chapter reviews causative agents, clinical manifestations, and management approaches for travel-related RTIs.

Causative Agents and Clinical Presentation

Respiratory infections may manifest as upper tract disease (rhinitis, sinusitis, otitis, pharyngitis, epiglottitis, tracheitis), lower tract disease (bronchitis, pneumonia), or both. Systemic manifestations may include fever, headache, and myalgia. The vast majority of RTIs are caused by agents with global distribution.

The usual causative agents of acute upper RTIs are listed in Box 59.1 . Most upper RTIs are caused by viruses, evolve as uncomplicated disease, and resolve without specific treatment. Acute coryzal illness, traditionally referred to as a “common cold,” manifests as nasal discharge and obstruction, sneezing, and sore throat, and is most commonly caused by viruses, including rhinovirus, parainfluenza virus, influenza virus, respiratory syncytial virus, adenovirus, enterovirus (especially coxsackievirus A21), coronaviruses, and metapneumonia virus. Acute laryngitis is characterized by hoarseness of voice with a deepened pitch, with possible episodes of aphonia. Often these signs are associated with those of coryza and pharyngitis. Common causes of laryngitis include parainfluenza virus, rhinovirus, influenza virus, and adenovirus. Less frequently, laryngitis can be caused by bacteria including Corynebacterium diphtheriae, Branhamella catarrhalis , and Haemophilus influenzae . Pharyngitis is also most commonly viral in origin, although streptococcal disease accounts for a significant minority. Other causes of pharyngitis include Epstein-Barr virus (EBV) and the human immunodeficiency virus (HIV).

Most Common Etiologic Agents of Upper Respiratory Tract Infections

Alt-text: Box 59.1

Lower respiratory tract infections (LRTIs) are characterized by bronchial and/or pulmonary parenchymal involvement. The most common etiologic agents of pneumonia are listed in Box 59.2 . Viruses commonly occur, but bacteria are responsible for a significant proportion of community-acquired cases of LRTI, and include Streptococcus pneumoniae and H. influenzae , as well as Mycoplasma spp. and Chlamydia spp. , Legionella spp., and mycobacteria (TB). 5 Fungal and parasitic involvement of the lung is also well recognized in travelers. Young children may sometimes be affected by severe forms of tracheobronchitis and croup, characterized by the stridorous croup cough. The majority of these cases are due to viruses.

Most Common Etiologic Agents of Pneumonia and/or Pulmonary Involvement

Alt-text: Box 59.2

Travel destination, exposure, and activities should be considered in returned travelers with an RTI, as shown in Table 59.1 . A list of common manifestations and complications of RTIs is presented in Box 59.3 .

Diagnostic Possibilities Based on Region of Travel

Common Manifestations and Complications of Respiratory Tract Infections and Common Etiologic Agents of Otitis Media

Alt-text: Box 59.3

Epidemiology

Steffen et al. estimated the monthly incidence of acute febrile RTIs to be 1261/100,000 travelers. 1 In that analysis, RTI ranked third after travelers' diarrhea and malaria among all infectious problems of travelers. However, that rate, which is equivalent to 0.2 episodes/person/year, is much lower than the incidence of common respiratory diseases among adults in the United States. 6 The difference is likely to be attributable to underreporting among travelers, because a large proportion of RTIs are mild, not incapacitating, and not reported.

In the literature, there are large variations in the proportion of respiratory infections among all causes of illness in returning travelers. Comparison among studies, however, is difficult, and differences are likely to reflect diverse diagnostic procedures and definitions of syndromes rather than true epidemiologic differences. Still, RTIs consistently rank among the most frequently diagnosed and/or reported conditions among travelers. Attack rates in reported studies have ranged from 5% to 40%. 7 , 8 , 9 , 10 , 11 , 12 , 13

In a large database of ill travelers from all continents within the GeoSentinel Surveillance System, Freedman described a frequency of respiratory disorders of 77 per 1000 ill returned travelers, ranging from 45/1000 in the Caribbean to 97/1000 in Southeast Asia. 2 In that analysis, respiratory disorders that prompted the seeking of medical care were less commonly reported than systemic febrile illnesses, acute diarrhea, dermatologic disorders, chronic diarrhea, and nondiarrheal gastrointestinal disorders. 2 Using the same database, Leder and colleagues reported that upper and lower respiratory diagnoses were found in 11% of all travelers. Most respiratory illnesses were due to infections with a worldwide distribution, including nonspecific upper respiratory infections, influenza or influenza-like illness, bronchitis, and pneumonia (lobar and atypical). Influenza A, B, or H1N1 was diagnosed in 8% of travelers with a respiratory illness. There were 35 cases of legionellosis. 14

O'Brien et al. studied a group of 232 sick travelers at a tertiary hospital in Australia who had largely traveled through Asian countries: RTIs were second after malaria, accounting for 24% of cases. 15 In that series, lower tract infections accounted for 50% of all RTIs, and were almost equally distributed between bacterial pneumonia and influenza. 15 Bacterial pneumonia was significantly more common in patients aged >40 years, with an odds ratio (OR) of 5.5. One-quarter of upper tract infections were due to group A Streptococcus . In a multicenter hospital study in Italy, of 541 travelers with fever, 8.1% of the patients had a respiratory syndrome, one-third of whom had pneumonia. TB was responsible for 29% of pneumonia cases in this cohort. Among cases with RTI and no signs of pneumonia, malaria was the underlying disease in 11 of 27. 16

In an analysis of GeoSentinel data on ill children after international travel, approximately 86% of ill children had four major syndromes: 28% had a diarrheal process; 25% had a dermatologic disorder; 23% had a systemic febrile illness; and 11% had a respiratory disorder. Upper RTI (38%), hyperactive airway disease (20%), and acute otitis media (17%) accounted for the majority of the cases of respiratory syndrome in these children. 17 In a Swiss study, Hunziker et al. found that leading diagnoses in children aged up to 16 years who presented with travel-associated illness were diarrhea (39%), respiratory (29%), and febrile/systemic illness (13%). Among travelers returning from Asia and America (South, Central, and North), respiratory illness was the most frequent diagnosis. 18

Risk Factors

In the GeoSentinel data, women were more likely than men to present with upper RTI associated with travel (OR 1.3). 8 Prolonged travel, travel involving visiting friends and relatives, and travel during the Northern Hemisphere winter increased the odds of being diagnosed with influenza and lower respiratory tract infection rather than upper tract disease in this cohort, and male gender was associated with twofold increased risk odds of pneumonia compared with female gender. 8

Air travel itself is not a major risk factor for transmission of RTI owing to the high cabin air exchange rate, air filtering, and relatively laminar-down pattern air flow active during flight, 19 although sitting in close proximity to a person who is highly infectious can result in infection. 20 , 21 , 22 Respiratory and intestinal infections are the most common diagnosis for passengers and crew seeking medical care on board ships. 23 Reasons for increased susceptibility of cruise ship travelers to respiratory infections may include contaminated ventilator cooling systems and spas, the use of hot tubs, common points-of-fomite contact (e.g., salad bars), as well as passenger factors such as age, underlying illnesses, and physical condition. 24 , 25

Infants, small children, the elderly, and subjects with chronic tracheobronchial or cardiopulmonary diseases are at increased risk of developing severe clinical consequences from RTIs. In a study by Gautret et al., respiratory disease ranked as the second most frequent reason for presentation to a GeoSentinel site in the older adults (age >60 years). Older travelers had a greater proportionate morbidity from lower RTI, including pneumonia and bronchitis. 26

Transmission

The spread of agents such as streptococci or meningococci is by direct, person-to-person contact, and via large droplets. These droplets usually fall to the ground within 1 m (3 ft) of an infectious person. Other pathogens are transmitted by tiny droplet nuclei (<10 µm diameter) that can be dispersed widely and randomly, can remain viable in the air for hours, and may be inhaled and pass easily through the narrow bronchioles. These agents can lead to infection in a large number of people, presenting as “clusters” or outbreaks of disease among those exposed. Measles and Mycobacterium tuberculosis can disseminate in this way. Influenza is transmitted by droplets and fomites.

Legionellosis is a respiratory disease with a unique chain of transmission. It is a bacterium that multiplies in water systems, often within free-living ameba, forming biofilms in cooling towers, water pipe fittings, and showers. Legionella can be disseminated in the aerosols generated by showerheads, whirlpools, and cooling systems. Such transmission contributes to outbreaks in hotels and cruise ships. 25

Management of Respiratory Tract Infections

An example of a decision algorithm for approaching patients with an RTI is presented in Figs. 59.1 and 59.2 . A syndromic management algorithm should effectively differentiate upper from lower RTIs, incorporating probable causative agents to guide treatment decisions. It should also assist in identifying complications that require specific treatment approaches. For practical purposes, a cough with rhinorrhea, or either of these with headache, fever, or shortness of breath, can be used to generally define an RTI.

Decision algorithm for acute upper respiratory tract infections.

Decision algorithm for acute lower respiratory tract infections.

Among upper RTIs (see Fig. 59.1 ), the isolated coryzal syndrome is rarely a cause of medical consultation. No additional diagnostic procedures are required and treatment is usually supportive. The diagnosis of laryngitis is also clinical, and treatment is usually supportive. Although the diagnosis of pharyngitis is also clinical, it is important to identify individuals with pharyngitis caused by group A streptococcal infection from other causes to lessen the likelihood of subsequent sequelae, including glomerulonephritis and rheumatic fever. Bacterial pharyngitis is reportedly associated with more severe pharyngeal pain, odynophagia, and higher fever, with grayish-yellow exudate on the tonsils and enlarged cervical lymph nodes. However, clinical criteria are unreliable to identify bacterial pharyngitis/tonsillitis because a typical presentation occurs in <50% of cases. Rapid antigen detection tests are available with a specificity >95% when compared with blood-agar plate cultures and sensitivity of 80%–90%, and should generally be performed in patients ill enough to seek medical care for pharyngitis, especially in young children. A negative rapid test should be followed by a confirmatory throat culture in children and adolescents but not necessarily in adults. Nucleic acid amplification tests including isothermal loop amplification are also available in some locations with a high degree of specificity and sensitivity as well as a rapid turnaround time. A treatment course with penicillin or amoxicillin for 10 days is appropriate to treat pharyngitis due to Streptococcus pyogenes . Diphtheria is a rare cause of pharyngitis, with a potentially fatal outcome. It is characterized by a thick and gray pharyngeal and tracheal membrane that bleeds upon attempted removal. Diagnosis is based on clinical recognition and culture isolation of a toxigenic strain of C. diphtheriae . The mainstay of therapy is diphtheria antitoxin, associated with antibiotic treatment with penicillin or macrolides. Vaccination effectively eliminates the risk of travel-related pharyngeal diphtheria.

Otitis media and sinusitis can complicate air travel secondary to barotrauma. Viral and bacterial causes are common, and empiric treatment usually involves some combination of supportive care and hydration, with or without antibiotics. If an antibiotic is prescribed, it should primarily target an S. pneumoniae infection. Upper RTIs can occasionally be complicated by peritonsillar and retropharyngeal abscess formation. Treatment usually involves mechanical drainage and antibiotics.

Clinical signs suggestive of pneumonia include productive cough, thoracic pain, and shortness of breath. Examination usually discloses pulmonary crepitation, rhonchi, and adventitial sounds. Chest imaging should be used to further characterize and define pulmonary involvement. Complications of pneumonia include pulmonary cavitation, pneumothorax, and empyema formation. In many facilities, it is now standard to collect nasopharyngeal swabs or washings from patients with severe RTIs and pneumonia, and to apply rapid antigen tests to assess for common respiratory viruses, including influenza, parainfluenza, respiratory syncytial virus, adenovirus, and metapneumonia virus. Although the majority of cases with radiologic evidence of pneumonia may still have a viral infection, the proportion of cases due to bacteria is high enough to usually warrant systematic antibacterial treatment, especially if a viral screen is unrevealing. The chest film is not helpful in making a specific etiologic diagnosis; however, lobar consolidation, cavitation, and large pleural effusions support a bacterial cause. Pneumococcal disease is often characterized by abrupt onset of fever, cough, rapid respiration, and lobar consolidation on chest film. Atypical pneumonias caused by Mycoplasma pneumoniae and Chlamydophila pneumoniae may be characterized by gradual onset of symptoms, cough progressive from dry to productive, chest film worse than symptoms, and normal peripheral white blood cell counts. Overall, however, the clinical presentation is not specific enough to make an etiologic diagnosis, and effective methods to recognize the causative agent of pneumonia are not available. The sputum Gram stain is a simple, quick, and inexpensive procedure, but its helpfulness in establishing a specific etiologic diagnosis is uncertain. The utility of the sputum culture is also unclear, since the procedure is insensitive: Only half of patients with pneumonia produce sputum and contamination occurs in one-third. An advantage of routine sputum Gram stain and culture is that these procedures would capture rare causes of pneumonia such as TB and melioidosis in travelers. Because the cause of pneumonia cannot be determined on the basis of any specific clinical, radiographic, or laboratory parameter, antibiotic therapy is usually initiated empirically. Treatment should be effective on S. pneumoniae , the most frequently responsible agent, and on agents of atypical pneumonia: M. pneumoniae , C. pneumoniae , and legionella infections.

A thorough travel and exposure history ( Box 59.4 ) can also help identify diagnostic possibilities (e.g., legionella), and the differential in immunocompromised patients can be quite broad.

Important Environmental Factors in Respiratory Tract Infections

Alt-text: Box 59.4

Pneumonia or pulmonary findings with eosinophilia in a traveler may also suggest specific diagnoses ( Box 59.5 ). 27

Causes of Pulmonary Involvement and Eosinophilia

Acute Ascaris lumbricoides infection (Loeffler syndrome)

Strongyloides stercoralis infection (Loeffler syndrome)

Acute hookworm infection (Loeffler syndrome)

Mycobacterium tuberculosis

Coccidioides immitis

Paragonimus spp.

Visceral larva migrans

Acute Schistosoma spp. infection (Katayama fever)

Dirofilaria immitis

Tropical pulmonary eosinophilia (lymphatic filariasis)

Alt-text: Box 59.5

Prevention in Travelers

Prevention of RTIs in the traveler as in all individuals usually relies on behavioral changes (hand-washing or hand disinfection with alcohol-based liquid sanitizers and avoidance of close contact with sick individuals), vaccination, and rarely chemoprophylaxis (e.g., antiinfluenza medication during an outbreak) ( Table 59.2 ).

Prevention of Respiratory Tract Infections in Travelers

Influenza, measles, diphtheria, pertussis, as well as pneumococcal and Hib-associated infections are vaccine-preventable diseases. All travelers should be up to date with antimeasles, antiinfluenza, antidiphtheria, and antipertussis vaccines (e.g., Tdap: tetanus, antidiphtheria, acellular pertussis vaccine). All children should be up to date with anti- H. influenzae b immunization (Hib) and pediatric pneumococcal polyvalent vaccine. All adults 65 years of age or older, or with certain indications, should be up to date for adult pneumococcal vaccination. 28 All travelers should be up to date for immunization against influenza. 4 , 29

Control measures for legionellosis are based on the application of guidelines for maintaining safe water systems in international tourist locations and cruise ships. 30 The early recognition of outbreaks is exceedingly important in the management of individual cases of diseases such as legionellosis. The European Legionnaires' Disease Surveillance Network (ELDSNET) reports legionella cases diagnosed in patients who have been traveling within the likely incubation period of 2 weeks, together with geographic location of suspected source of transmission. Members of the group report cases of legionnaires disease to the coordinating center, which then notifies all members of any disease cluster. Other international global and regional surveillance networks, including GeoSentinel, TropNet, and EuroTravNet, play a pivotal role in early detection and public warning of travel-related epidemics. 31 , 32

International health authorities may impose and have imposed public health interventions during worrisome outbreaks (e.g., H5N1 and H1N1 influenza, and SARS), including animal culling, travel restrictions, screening at airports and points of arrival and departure, and quarantine in efforts to limit the spread of respiratory infections.

Infections of the Respiratory Tract Associated With Epidemics

Severe acute respiratory syndrome.

SARS can serve as a paradigm infection that underscores the risk and consequences of international travel, and the role that travelers can play in the global, rapid, and lethal spread of a highly pathogenic RTI. As this severe atypical pneumonia began to spread from China, in mid-March 2003, the World Health Organization (WHO) issued a global alert about the outbreak and subsequently named this condition severe acute respiratory syndrome. The virus spread among travelers, with a focused outbreak radiating from a single Bangkok hotel to a number of countries, with subsequent ongoing spread. From November 2002 to July 2003, 8098 cases and 774 deaths were reported from 28 countries, with a fatality rate of 9.6%. 33 A global public response was initiated. Fortunately, since April 2004 not a single case of SARS has been reported worldwide.

Avian Influenza

Human infections with avian and zoonotic influenza viruses have been reported. Human infections are primarily acquired through direct contact with infected animals or contaminated environments. In 1997 human infections with the H5N1 virus were reported during an outbreak in poultry in Hong Kong SAR, China. Since 2003 this avian virus has spread from Asia to Europe and Africa, and has resulted in millions of poultry infections, several hundred recognized human cases, and a high case-fatality rate. 34 In 2013 human infections with the H7N9 virus were reported in China. 35 Since then, the virus has spread in the poultry population across the country and resulted in several hundred human cases and many human deaths. Other avian influenza viruses have resulted in sporadic human infections including the H7N7 and H9N2 viruses. Some countries have also reported sporadic human infections with swine influenza viruses, particularly the H1N1 and the H3N2 subtypes. In many patients infected by A(H5) or A(H7N9) avian influenza viruses, common initial symptoms are high fever (≥38°C) and cough. Signs and symptoms of lower respiratory tract involvement including dyspnea or difficulty breathing are common. Complications of infection include hypoxemia, multiple organ dysfunction, and secondary bacterial and fungal infections. The case fatality rate for A(H5) and A(H7N9) subtype virus infections among humans is much higher than that of seasonal influenza infections. Evidence suggests that some antiviral drugs, notably oseltamivir and peramivir, can reduce the duration of viral replication and improve survival. Since their availability may be limited in some areas, travelers with a high likelihood of exposure (poultry workers, veterinarians, or medical doctors in endemic areas) should consider bringing these drugs with them. Currently no vaccines for avian influenza in humans are commercially available. Particular attention should be given to travelers planning to visit areas endemic for avian influenza in poultry and where human cases have occurred. Such areas are currently found in Asia, Africa, and the Middle East. Advice should focus on avoiding contact with patients suffering from respiratory disease, and contact with birds and their excreta at live bird markets or farms, as well as avoiding contact with and consumption of insufficiently cooked poultry products. 4 Human-to-human transmission has fortunately been highly sporadic thus far, and limited to very close contacts. However, should such viruses mutate to become steadily transmissible in the human community, a new deadly pandemic influenza could emerge.

Influenza is the most important viral respiratory infection of travelers and nontravelers. Several changes in our globalizing world contribute to the growing importance of travelers in spreading influenza: (i) steady increase in total travel volume worldwide, (ii) advent of mass tourism, and (iii) increasing numbers of immunocompromised and elderly travelers. 4 Mutsch et al. found that 1% of the travelers enrolled in a study of influenza virus infection in persons traveling to tropical and subtropical countries seroconverted to influenza during their trip, and that 40% of those who seroconverted had sought medical attention during travel. Influenza virus infections were acquired largely in Asia (48%), Africa (28%), and Latin America (25%). 36 Travelers acquire influenza both as sporadic cases and as clusters from common sources aboard ships, airplanes or in airports, and in tour groups. All described outbreaks are caused by the type A virus, and are characterized by involvement of a large proportion of the population at risk and the explosive nature of outbreaks. Data collected from GeoSentinel and EuroTravNet indicate that in 2008, prior to the H1N1 pandemic, the number of influenza confirmed cases was at just 0.1%. During 2009, however, the number of confirmed influenza cases in GeoSentinel rose to 11%, 12%, 18%, and as high as 32% with the majority of these attributable to H1N1. 7 , 37 Influenza is a common infection also among hajj pilgrims, with approximately 20,000 estimated cases per hajj season. 38

Influenza is a self-limited disease that produces high morbidity and is responsible for lethal cases, most commonly among the youngest and eldest. The hallmark of the clinical presentation of influenza is a febrile illness with cough. Fever characteristically lasts 3–5 days, but dry cough may persist for much longer. Pneumonia is the most frequent complication, either from direct viral involvement or bacterial superinfection, the latter most commonly caused by S. pneumoniae, H. influenzae , group A Streptococcus , and Staphylococcus aureus . Otitis media and sinusitis are other serious complications. Complications are more frequent and severe among patients with chronic diseases of the lung or heart.

Diagnosis is usually based on clinical criteria during an outbreak. Although rapid influenza diagnostic tests are often employed because of their ease of use and rapidity, they can have suboptimal sensitivity to detect influenza virus infection, particularly for novel influenza viruses. Sensitivities of rapid diagnostic tests are generally only 50%–70%, compared to viral culture or reverse transcription polymerase chain reaction (PCR). Specificities of rapid diagnostic tests are generally higher, approximately 95%–100%.

If there is clinical suspicion for influenza in a patient at high risk for complications, early empiric treatment should be given regardless of a negative rapid diagnostic test result, and another type of test (e.g., reverse transcription, PCR, direct fluorescent antibody, or viral culture) may be performed for confirmation. Treatment is symptomatic in most cases. For severe cases and for patients at highest risks of complications and severe disease, antiinfluenza therapy with neuraminidase inhibitors can be used.

Northern and Southern Hemisphere influenza vaccines may be different. Influenza in the Northern Hemisphere occurs mainly from October–February; influenza in the Southern Hemisphere predominantly occurs April–August. As one approaches the equator, influenza circulates year round. Travelers are at high risk of influenza year round since they are often mingling with other travelers from current influenza zones or traveling directly to those zones. There are several ways to decrease the risk of acquiring influenza. Hygienic measures, including active ventilation of crowded places, hand sanitation, and (possibly) wearing a facemask, can reduce the risk of spreading influenza. 4 Select elderly or other high-risk groups of travelers could be advised to bring a neuraminidase inhibitor for influenza early treatment, if access to medical care at the destination will be limited. 4 Unless contraindicated, international travelers should be vaccinated against seasonal influenza.

Middle East Respiratory Syndrome Coronavirus

MERS-CoV is a viral respiratory illness that has been reported in Bahrain, Iran, Jordan, Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, United Arab Emirates (UAE), and Yemen. Most patients diagnosed with MERS have developed severe respiratory illness with shortness of breath and cough, and 3 of 10 patients have died. Secondary transmission in households and health care facilities have led to focused outbreaks. MERS-CoV has been reported in some camels; and some patients with MERS have had contact with camels. MERS should be considered in anyone with a severe respiratory illness within 14 days of travel to a country in or near the Arabian Peninsula, and contacts of sick patients who themselves traveled. Travel-related cases have been reported in Algeria, Austria, China, Egypt, France, Germany, Greece, Italy, Malaysia, Netherlands, Philippines, Republic of Korea, Thailand, Tunisia, Turkey, United Kingdom, and United States. Diagnosis is PCR based. Treatment is supportive. Patients should be placed on respiratory and contact precautions.

Legionellosis

Legionella infections occur worldwide as sporadic cases. Endemic legionellosis is responsible for approximately 2% of community-acquired pneumonia; the highest incidence is in people >40 years of age, but only a fraction of cases are recognized. According to the Centers for Disease Control and Prevention (CDC), 20% of patients hospitalized with legionnaires disease in the United States acquired their infection while traveling. 39 Between 2000 and 2010, 7869 hotel-associated cases (and 994 clusters) and 105 ship-associated cases of legionnaires disease (with 366 deaths) were reported by ELDSNET. 40 For 2015, 1141 travel-associated legionnaires disease cases were reported through ELDSNET, 20% more than in 2014. A total of 167 new travel-associated clusters were detected in 33 countries, compared with 132 in 2014, 110 in 2013, and 99 in 2012. In 2015, 60% of the detected clusters of travel-associated legionnaires disease were characterized by initial cases from several different countries. 41 The Mediterranean region in Europe has been the origin of most reported outbreaks, but no area is excluded from risk, as exemplified by the identification of a cluster of cases associated with a hotel in Bangkok. 42

Transmission is airborne, but the source of infection is the environment rather than other persons. The incubation period is classically considered as 2–10 days, although 16% of 188 cases described in a large outbreak in the Netherlands reported incubation periods >10 days. 43 The clinical spectrum is wide, ranging from subclinical to lethal manifestations. The overt picture of legionellosis is that of a lobar pneumonia with abrupt onset characterized by high fever, severe headache, and confusion. 44 Patchy infiltrates are often present bilaterally. Mortality may be as high as 20% if diagnosis and antibiotic treatment are delayed. Diagnosis is usually based on detection of antigen in urine (for L. pneumophila type 1, with 80% sensitivity and 99% specificity). Culture can also be employed. Where available, PCR can be used to identify L. pneumophila from bronchoalveolar lavage fluid and other clinical specimens. Treatment is often empiric: macrolides are the treatment of choice. Co-trimoxazole and fluoroquinolones are also effective.

Tropical and Geographically Restricted Respiratory Infections

Travelers may be at risk of a number of geographically restricted respiratory infections, as well as those associated with travel to resource-limited areas.

Melioidosis

Melioidosis is caused by a gram-negative rod, Burkholderia pseudomallei . Cases usually occur within 20° north to 20° south of the Equator, with the vast majority of cases being reported in Southeast Asia and northern Australia. The bacterium is free-living in soil and water, and humans can become infected through inhalation or through direct contact (wounds). Melioidosis remains a risk for travelers to endemic areas, especially those with exposure to wet-season soils and surface water. 45 B. pseudomallei was one of the more frequent isolates from travelers and patients affected by the 2005 Asian tsunami. 46 Risk factors for clinical disease include diabetes, chronic alcoholism, chronic lung disease, and chronic renal disease.

Septicemia, pneumonia, cellulitis, and abscess formation are the most frequent manifestations. Lung involvement consists of acute necrotizing pneumonia or chronic granulomatous or fibrosing lung disease mimicking TB. The diagnosis of pulmonary melioidosis is difficult. Physicians in western countries should be aware of the possibility of melioidosis not only in patients originating from endemic areas but also in patients returning from travel in those regions. Because it can manifest months or years after leaving the endemic area, patients may not remember the exposure event and its potential relationship to their symptoms. The diagnosis can be confirmed by Gram stain and culture of respiratory specimen and/or blood. The presumptive diagnosis of melioidosis may be based on a positive indirect hemagglutination assay (IHA) or enzyme-linked immunosorbent assay (ELISA) serology in the appropriate clinical setting. 47 , 48 , 49 IHA titers above 1 : 80 are suggestive of active infection, but can also be seen in asymptomatic subjects in endemic regions. 48 Treatment of patients with melioidosis usually involves meropenem or ceftazidime plus trimethoprim-sulfamethoxazole or doxycycline for a period of at least 2–6 weeks. Therapy should be guided by antimicrobial susceptibility tests. For severe disease, prolonged treatment for 2–6 months is recommended to prevent relapses. A vaccine against melioidosis is not commercially available; the best way to prevent infection is by avoiding contact with contaminated soil or water; travelers should be advised to always wear shoes. 45

Leptospirosis

Pulmonary involvement in leptospirosis is not rare, and usually manifests as a dry cough, or occasionally as a cough with blood-stained sputum.

Leptospirosis is due to several serovars of a spirochetal bacterium, often Leptospira interrogans , and is a zoonosis . Transmission occurs by accidental contact with water or soil contaminated with the urine of an infected animal, often a rodent. Outbreaks have occurred among adventure travelers on group tours, 50 and leptospirosis with pulmonary hemorrhage has been noted with increasing frequency. 51 , 52 Clinical manifestation of leptospirosis may vary from asymptomatic infection to fulminant disease. Severe cases are characterized by liver and renal failure, with mortality as high as 30% in untreated cases. Pulmonary complications often contribute to the fatal outcome: They include extensive edema and alveolar hemorrhages in the context of an acute respiratory distress syndrome (ARDS) episode. The radiologic findings are those of ARDS. The diagnosis requires the isolation of the bacteria from blood or urine samples, but this is rarely performed. The diagnosis usually rests on clinical recognition and serology.

Prevention of leptospirosis is difficult, especially in tropical areas where the disease is not limited to high-risk groups. Prevention of rodent-human contacts is important. A human vaccine and the use of tetracycline chemoprophylaxis (200 mg/week) are available but are rarely indicated.

Cutaneous disease is the most commonly observed form of human anthrax. Pulmonary anthrax is less common but more deadly, and is caused by inhalation of Bacillus anthracis spores . Naturally acquired anthrax may occur in developing countries, where the risk is still significant in rural parts of Asia, Africa, Eastern Europe, South and Central America as a result of contact with contaminated soil or animal products; a few cases of anthrax have been described in travelers who import souvenirs.

Inhalation anthrax is notable for its absence of pulmonary infiltrate on chest imaging, but the presence of extensive mediastinal lymphadenopathy, pleural effusions, and severe shortness of breath, toxemia, and sense of impending doom. The incubation period is 2–5 days, but spores can germinate up to 60 days after exposure. Pathogenesis is mediated by a toxin responsible for hemorrhage, edema, and necrosis. The presenting symptoms are nonspecific, with mild fever, malaise, and a nonproductive cough. After a period of a few days in which the patient's condition apparently improves, a second phase begins with high fever, respiratory distress, cyanosis, and subcutaneous edema of the neck and thorax. Crepitant rales are evident on auscultation. Inhalation anthrax is almost invariably fatal with a very short time between the onset of the second phase, mediastinal signs, and death. The diagnosis of inhalation anthrax is extremely difficult outside of epidemic conditions. Direct examination and Gram stain of the sputum specimen are unlikely to be positive. A serologic ELISA test is available, although a significant increase in titer is usually obtained only in convalescent subjects who survive. The most useful bacteriologic test in case of suspicion, however, is a blood culture demonstrating B. anthracis . Treatment of inhalation anthrax should be as early as possible and usually involves a carbapenem, penicillin, doxycycline, and fluoroquinolone such as ciprofloxacin. Ancillary treatment to sustain vascular volume, cardiac, pulmonary, and renal functions is essential.

Plague is caused by Yersinia pestis , a gram-negative coccobacillus. It is considered a reemerging disease because of the increase in the number of reported cases worldwide, the occurrence of epidemics (such as the one in India in 1994), and the gradual expansion in areas of low endemicity (including the United States). The most heavily affected African countries are Madagascar, Democratic Republic of Congo, Uganda, the United Republic of Tanzania, and Mozambique. The Central Asian region has active plague foci in the Central Asian desert, affecting Kazakhstan, Turkmenistan, and Uzbekistan. Plague foci are distributed in 19 provinces and autonomous regions of China, and the incidence has been increasing since the 1990s. Permanent plague foci exist in the Americas among native rodent and flea populations in Bolivia, Brazil, Ecuador, Peru, and the United States. 53 The 1994 Indian epidemic, where a total of 5150 suspected pneumonic or bubonic cases occurred in a 3-month period, caused travel and trade disruption and resulted in severe economic repercussions. 54 Travelers are rarely affected by plague while visiting endemic areas (e.g., no visitors were affected during the 1994 epidemic in India). Campers or visitors staying in rodent-infested lodges are exposed to the highest risk of infection.

In humans, pneumonia may follow septicemia or may be a primary event in the case of airborne transmission (though pneumonic plague is currently very rare). Plague should be suspected in febrile patients who have been exposed to rodents or other mammals in known endemic areas. The presence of buboes in this setting is highly suspicious. The bacterium may be isolated on standard bacteriologic media from culture samples of blood or bubo aspirates. The Gram stain may reveal gram-negative coccobacilli with polymorphonuclear leukocytes. Rapid diagnostic tests such as the direct immunofluorescence test for the presumptive identification of Y. pestis F1 antigen are of interest for the rapid management of patients with the suspicion of disease. 55 Serologic tests to detect antibodies to the F1 antigen by passive HAI or ELISA method are available. A fourfold increase in titer (or a single titer of 1 : 16 or more) may provide presumptive evidence of plague in culture-negative cases. Antibiotic treatment should be started on the basis of clinical suspicion, usually involving an aminoglycoside (streptomycin, gentamicin) and/or doxycycline or chloramphenicol.

Pulmonary infections present a particular risk for human epidemics owing to the contagiousness of the organism. Doxycycline (100 mg twice daily for 7 days) prophylaxis of family members of index cases is indicated within the standard 7-day maximum plague incubation period.

Paragonimiasis

Paragonimiasis is caused by a lung fluke, often Paragonimus westermani . Humans become infected through the ingestion of undercooked or raw crabs, crayfish, or their juices. The infection is endemic in Southeast Asia (including Thailand, the Philippines, Vietnam, China, and Taiwan), South and North America, 56 and Africa, with most cases being reported in Asia. The disease is well described, although rare in travelers to endemic regions. 57 The incubation period may vary from one to several months after exposure.

The disease presents as a chronic bronchopneumonic process with productive cough, thoracic pain, and low-grade fever. The worms produce extensive inflammation and cavity formation, and the infection should be considered in individuals with nodular cavitating lung lesions and rusty-brown bloody sputum. Acute paragonimiasis can present as pneumothorax as the worms invade the lung tissue. Diagnosis usually rests on clinical recognition and detection of the worms' eggs in expectorated sputum. Treatment involves praziquantel. Prevention is based on avoiding eating raw crayfish and crabs.

Coccidioidomycosis and Histoplasmosis

Coccidioidomycosis and histoplasmosis are two fungal infections acquired by the respiratory route and often involve the respiratory system. Coccidioidomycosis is caused by inhalation of Coccidioides immitis , a dimorphic fungus found in dust and soil. The pathogen is present only in semiarid regions of the Americas. Symptomatic disease develops in approximately 40% of individuals infected by C. immitis , presenting as a flulike syndrome. The radiologic finding is often that of hilar pneumonia with lymphadenitis and pleural involvement. In a well-described outbreak of coccidioidomycosis in a 126-member church group traveling to Mexico, the average incubation period was 12 days (range 7–20 days); chest pain was present in 76% and cough in 66% of the affected travelers. 58 The diagnosis is serologic, and antibodies appear 1–3 weeks after the onset of symptoms.

Histoplasmosis is caused by infection with a soil-inhabiting dimorphic fungus, Histoplasma capsulatum . The agent is ubiquitous, but diffusion is higher in the tropical belt and the United States. Outbreaks of acute histoplasmosis among travelers have been repeatedly reported. 59 , 60 , 61 The disease may evolve as a mild, spontaneously resolving condition, but severe and systemic disease may develop in immunocompromised patients. Acute pulmonary histoplasmosis (APH) in returning travelers typically presents as a flulike illness with high-grade fever, chills, headache, nonproductive cough, pleuritic chest pain, and fatigue. Symptom onset is usually 1–3 weeks following exposure and most individuals recover spontaneously within 3 weeks. Chest x-ray may show patchy infiltrates or interstitial pneumonia. Diagnosis may be extremely difficult unless the disease is considered in the differential diagnosis, and most cases are unrecognized and considered as bacterial bronchitis or influenza. Confirmation of the disease usually involves a urine and serum antigen assay, or comparison of acute-phase and convalescent-phase serum specimens. Antifungal treatment is not usually indicated for mild to moderate APH in immunocompetent persons. For patients who continue to have symptoms for >1 month, itraconazole is recommended. Patients with moderately severe to severe APH should receive liposomal amphotericin B followed by itraconazole.

Tuberculosis

TB is a widely distributed infection and a leading cause of human morbidity and mortality. Travel can increase the risk of TB, especially among individuals traveling to high burden countries, those visiting friends and relatives, those performing health care or service work overseas, and those traveling for extended periods. Most individuals who become infected with Mycobacterium tuberculosis do not develop the disease and are diagnosed as having latent TB infection (LTBI), often on the basis of a skin test or interferon-gamma-based assays. Multidrug-resistant tuberculosis (MDR TB) is now present in many regions, including a number of sites in Eastern Europe and parts of Southeast Asia popular with travelers. 62

TB Among Travelers From Low-Endemic to High-Endemic Areas.

There is evidence of an association between travel and an increased risk for LTBI. Lobato first demonstrated that US children who had traveled abroad had a significantly higher probability of having a positive tuberculin skin test than children without a history of travel. 62 Cobelens et al. estimated the risk of acquiring M. tuberculosis infection among long-term (≥3 months) Dutch travelers to Africa, Asia, and Latin America as 3.3% per year. 63 Abubakar et al. provided the first evidence in the United Kingdom that travel to countries with high levels of TB infection may be an independent risk factor for acquiring LTBI. 64 A systematic review using tuberculin skin testing (TST) conversion as a surrogate for LTBI calculated the cumulative incidence of LTBI in long-term travelers to be 2%. 65 Other factors identified for increased TB risk among travelers were being a health care worker, a longer cumulative duration of travel, and a longer total time spent in TB-endemic countries. 63

Air travel itself is not considered a major risk factor for transmission of TB. 66 The risk of TB transmission on ships and trains has also been described but is similarly of little epidemiologic importance.

Active TB (as opposed to LTBI) was 16 times more likely to be reported in individuals seeking medical care at a GeoSentinel site among those born in low-income countries and who were now living in high-income countries and traveling to their region of birth to visit friends and relatives than it was among those born and living in high-income countries and traveling to low-income countries to visit friends and relatives, and more than 60 times more common than it was among tourist travelers. 66 Despite this, the evidence of association between actual travel (as opposed to demographics of travels) and active TB (as opposed to LTBI) is sparse. Where overall risk is judged to be sufficiently high, pretravel testing for LTBI (TST or interferon-gamma release assays) may be indicated. Travelers to high TB-endemic areas can employ behavioral modifications (i.e., individuals traveling to provide health care should use personal protective equipment in caring for patients with probable TB). Following travel, assessment should focus on establishing whether a significant risk of exposure to TB occurred, and on any signs or symptoms that may suggest active infection ( Fig. 59.3 ). Asymptomatic individuals who are considered at sufficient risk of exposure (or where direct contact with TB is known to have occurred) should be tested for LTBI. Symptomatic individuals should be evaluated for active TB. 62

Prevention of tuberculosis (TB) disease in long-term travelers: identification and treatment of new infections. IGRA, Interferon-gamma release assay; PPD, purified protein derivative tuberculosis skin test.

A vaccine (Bacillus Calmette-Guérin [BCG]) is available in many countries and many national guidelines recommend vaccination for children <5 years old traveling to TB-endemic countries for 1 month or longer.

Respiratory infections represent a frequent health problem for international travelers. The incidence is underestimated mainly because the majority of infections are mild and not incapacitating. Most are due to cosmopolitan agents, and “tropical” and/or geographically restricted infections are rare. The RTI of perhaps the most significance to travelers is influenza. Travelers represent the primary vehicle of the yearly spread of influenza around the globe, and are critical to the global spread of new pandemics. Effective antiinfluenza vaccines exist, and all travelers should receive yearly influenza immunization and be instructed in hand-washing and cough/sneeze hygiene. All travelers should also be up to date for other vaccines, including those that prevent RTIs, including measles, pneumococcal diseases, Hib, diphtheria, and pertussis. Clinicians caring for an ill returned traveler with an RTI should characterize the illness as upper or lower RTI, and consider the travel itinerary, exposure history, clinical manifestations, incubation period, and host-specific conditions.

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April 15, 2024

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Large study finds antibiotics aren't effective for most lower tract respiratory infections

by Georgetown University Medical Center

Use of antibiotics provided no measurable impact on the severity or duration of coughs even if a bacterial infection was present, finds a large, prospective study of people who sought treatment in U.S. primary or urgent care settings for lower-respiratory tract infections.

The study by researchers at Georgetown University Medical Center and colleagues appeared in the Journal of General Internal Medicine.

"Upper respiratory tract infections usually include the common cold, sore throat , sinus infections and ear infections and have well established ways to determine if antibiotics should be given," says the study's lead author, Dan Merenstein, MD, professor of family medicine at Georgetown University School of Medicine.

"Lower respiratory tract infections tend to have the potential to be more dangerous, since about 3% to 5% of these patients have pneumonia. But not everyone has easy access at an initial visit to an X-ray, which may be the reason clinicians still give antibiotics without any other evidence of a bacterial infection . Plus, patients have come to expect antibiotics for a cough , even if it doesn't help. Basic symptom-relieving medications plus time brings a resolution to most people's infections."

The antibiotics prescribed in this study for lower tract infections were all appropriate, commonly used antibiotics to treat bacterial infections. But the researchers' analysis showed that of the 29% of people given an antibiotic during their initial medical visit, there was no effect on the duration or overall severity of cough compared to those who didn't receive an antibiotic.

"Physicians know, but probably overestimate, the percentage of lower tract infections that are bacterial; they also likely overestimate their ability to distinguish viral from bacterial infections," says Mark H. Ebell, MD, MS, a study author and professor in the College of Public Health at the University of Georgia.

"In our analysis, 29% of people were prescribed an antibiotic while only 7% were given an antiviral. But most patients do not need antivirals as there exist only two respiratory viruses where we have medications to treat them: influenza and SARS-COV-2. There are none for all of the other viruses."

To determine if there was an actual bacterial or viral infection present, beyond the self-reported symptoms of a cough, the investigators confirmed the presence of pathogens with advanced lab tests to look for microbiologic results classified as only bacteria, only viruses, both virus and bacteria, or no organism detected. Very importantly, for those with a confirmed bacterial infection, the length of time until illness resolution was the same for those receiving an antibiotic versus those not receiving one—about 17 days.

Overuse of antibiotics can result in dizziness, nausea, diarrhea, and rash along with about a 4% chance of serious adverse effects including anaphylaxis, which is a severe, life-threatening allergic reaction; Stevens-Johnson syndrome, a rare, serious disorder of the skin and mucous membranes; and Clostridioides difficile-associated diarrhea. Another significant concern of the overuse of antibiotics is resistance. The World Health Organization released a statement on April 4, 2024, stating, "Uncontrolled antimicrobial resistance [due to the overuse of antibiotics] is expected to lower life expectancy and lead to unprecedented health expenditure and economic losses."

"We know that cough can be an indicator of a serious problem. It is the most common illness-related reason for an ambulatory care visit, accounting for nearly 3 million outpatient visits and more than 4 million emergency department visits annually," says Merenstein.

"Serious cough symptoms and how to treat them properly needs to be studied more, perhaps in a randomized clinical trial as this study was observational and there haven't been any randomized trials looking at this issue since about 2012."

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