viral and atypical pneumonias.pdf

COMMUNITY-ACQUIRED RESPIRATORY INFECTIONS IN CHILDREN 00954543 /96 $0.00 + .20

VIRAL AND ATYPICAL PNEUMONIAS

Brenda A. Latham-Sadler, MD, and Venita W. Morell, MD

VIRAL PNEUMONIAS

Even in the age of multigenerational antibiotics and ever-emerging antiviral agents the recognition, differentiation, and treatment of pneumonia in the pediatric age group continues to be a challenge. The focus of this article is limited to viral and atypical pneumonias. Viral or Mycoplasma pneumoniae infection has been detected in 17% to 31% of outpatient pneumonias studied. Most children with pneumonia are managed as outpatients; however, most published information about pneumonia has been derived from hospitalized patients."

Many cases of viral pneumonia may go unrecognized because the onset tends to be subtle and infected patients may not appear very ill. There are numerous viral agents capable of causing pneumonia in healthy, immunologically sound children. Respiratory syncytial virus (RSV) parainfluenza virus, and adenovirus are the most common viral causes. The two most common atypic pneumonias acquired by healthy children are mycoplasma and Chlamydia trackomatis. Accurate recognition of a viral cause can be complicated by difficulty isolating the viral agent. History and physical evidence along with techniques to diagnose and treat viral and atypical pneumonias accurately are explored. One of the most important things to remember is that characteristic features of different diseases serve only as a rough guide to form a best guess about an individual diagnosis. The frustrating reality is that a patient with a typical presentation of viral pneumonia really may have a bacterial infection and the same is true of patients with atypical pathogens. Effective recognition and treatment of pneumonia is complicated further because a viral or atypical infection may occur simultaneously with a bacterial infection. It has been found that 53% of outpatients with bacterial pneumonia had a concurrent viral infection." Despite bacterial, viral, and mycoplasmal cultures, the

From the Department of Family and Community Medicine, Bowman Gray School of Med- icine of Wake Forest University, Winston-Salem, North Carolina

PRIMARY CARE

VOLUME 23 - NUMBER 4 * DECEMBER 1996 837

838 LATHAM-SADLER & MORELL

cause of acute lower respiratory tract infection in children is often obscure, with 24% to 56% of cases having no pathogen identified.13

It is useful to understand the differences in presentation among pathogens so that treatment might be more targeted to the likely organism. This is particularly important if clinicians are to try to avoid the use of unnecessary antibiotics in the treatment of viral pneumonias.

CLINICAL MANIFESTATIONS

Pneumonia, an inflammation of the parenchyma of the lungs, can be classified in different ways. Anatomic classification, defining location of the infiltrate as lobar or lobular versus alveolar or interstitial, is possible. Classification based on infectious cause is diagnostically and therapeutically more relevant.' The causative agent in childhood pneumonia is most often viral, especially during the first several years of life. These viral agents invade and destroy the mucous membrane and may produce bronchiolitis, peribronchitis, and interstitial lesions. The cause of pneumonias in older children is similar to those seen in adults.

Cough and fever are the predominant clinical symptoms found in viral pneumonia. The hallmark finding in viral infections is replication of the virus in the respiratory epithelium causing symptoms mainly related to the disturbance of the ciliated cells of the respiratory epithelium. The fever is usually lower than that found in bacterial pneumonia. Most viral pneumonias are preceded by several days of upper respiratory tract symptoms such as rhinorrhea and pharyngitis, followed by the cough and fever.7 With progression of the disease from upper to lower tract, dyspnea, intercostal retractions, and nasal flaring are common in younger children. Wheezing or stridor may be more prominent in viral disease than bacterial, especially lower respiratory tract infection with RSV. Other findings such as cough, signs of respiratory difficulty (tachypnea, retractions, grunting, nasal flaring), and physical findings (rales, decreased breath sounds) may not be distinguishable from those in bacteria pneumonia. Fever is an inconsistent finding, and it correlates poorly with the severity of illness. The most common finding on auscultation of the chest in viral pneumonia is diffuse, coarse rhonchi.

CAUSE

Several factors influence the type of illness and severity of lower viral respiratory tract infections. These factors include age, sex (men are infected at a slightly higher rate than women), season of the year, and crowded living conditions. The peak attack rate for viral pneumonia is reached between the ages of 2 and 4 years. Pneumonia in children younger than 3 years of age is caused most commonly by RSV.3 Approximately 50% of all pneumonias in this age group are caused by RSV, and approximately 50% of all RSV pneumonias occur before 2 years of age.4 In most studies parainfluenza virus and adenovirus are the next most commonly identified viruses in acute lower respiratory tract infe~ti0ns.l~ When considering the timing of an infection, RSV is more prominent in winter, parainfluenza in late fall and winter, and influenza in late winter early spring.14 Rhinovirus, influenza virus, and herpes simplex virus all cause pneumonia in children but less often. Rare causes of viral pneumonia in children include cytomegalovirus, varicella zoster, and measles virus (Hecht's giant-cell pne~monia) .~

The greatest challenge in lower respiratory tract infections in children is dif- ferentiating potential pathogens. Paisley et all1 identified a single pathogen in only 53% of 102 children studied. Two pathogens were identified in 30%, three path-

VIRAL AND ATYPICAL PNEUMONIAS 839

ogens in 2%, and no pathogen was identified in 15%. Seventy-four percent of the children had viruses detected, and in 4 of these two viruses were present. Mixed viral-bacterial or viral-chlamydia1 infections were found in 29%. Ten percent had C. trachomatis detected, but in only one case was C. trachomatis the sole pathogen.

SPECIFIC VIRAL AGENTS

Respiratory Syncytial Virus

RSV is a major cause of bronchitis, bronchiolitis, and pneumonia in infants younger than 1 year of age and the most common respiratory tract pathogen of early childhood. RSV epidemics peak in January, February, and March. The diagnosis of RSV pneumonia can be made reliably based on the clinical presentation, age of the child, time of the year, and climate, as well as reports of other cases in the community. Severe infection is uncommon in the first 4 to 6 weeks of life. This is probably because of placenta transfer of antibodies from the mother.

Most infants present initially with coryza and pharyngitis and occasionally with otitis media. Cough may appear simultaneously but most often after 1 to 3 days. There also may be sneezing and low-grade fever at this time. Soon after the cough develops, wheezing becomes audible. Auscultation often reveals diffuse rhonchi, fine rales, and wheezes. Rhinorrhea usually is present throughout the illness with intermittent fever, although fever is an inconsistent finding in RSV infection. Progression to lower tract respiratory infection occurs in 10% to 40% of patients, producing varying degrees of bronchitis, bronchiolitis, and broncho- pneumonia. RSV bronchiolitis can be indistinguishable from RSV pneumonia. It is common to find both occurring simultaneously. As illness progresses, cough and wheezing increase with evidence of hyperexpansion of the chest and of intercostal and subcostal retractions. The respiratory rate increases and cyanosis occurs. The development of central cyanosis, tachypnea of more than 70 breaths/ minute, listlessness, and apneic spells are signs of severe life-threatening illness requiring hospitalization.

All RSV infections of the lower respiratory tract have their highest incidence in the sixth month of life, becoming less common after the 1st year of life.5 RSV is a persistent problem throughout childhood, causing 45% to 75% of all cases of bronchiolitis, 15% to 25% of childhood pneumonias, and 6% to 8% of all cases of croup.4 Recurrent infections are common. In older children and adults RSV usually manifests as a minor upper respiratory tract infection, but the infection can be passed on to younger children in the family, causing more severe illness. In epidemics, rate of community infection is very high, placing susceptible infants at particular high risk of becoming infected.

PARAINFLUENZA VIRUSES

After RSV, the next most common viral cause of lower respiratory tract infection in infants is parainfluenza virus. Most parainfluenza virus infections, however, are confined to the upper respiratory tract. Four serologic types of parainfluenza viruses cause disease in humans.* Types I, 11, and I11 cause symptomatic infection and are extremely common. Symptomatic reinfections occur. Infection with type IV is also common but is usually asymptomatic. Almost all children have been infected with parainfluenza type I11 by the age of 3. Of the children hospitalized with severe respiratory tract illness, parainfluenza accounts for about 15% of each of the cases of bronchiolitis, bronchitis, and pneumonia and is most


often caused by type 111. These viruses continue to be common causes of respiratory tract illness in adults.

INFLUENZA VIRUS

Influenza viruses are grouped into three broad serologic types: A, B, and C. Respiratory secretions of infected children contain large numbers of virus particles leading to transmission from person to person. Influenza virus types A and B play a particularly significant role in viral infections seen in school-aged children. Dur- ing winter months, up to 75% of such children may be infected. The onset of illness is abrupt and marked by coryza, conjunctivitis, pharyngitis, and dry cough. More than any other respiratory virus, influenza is accompanied by systemic signs of fever, myalgia, malaise, and headache. Symptoms may localize, producing an iso- lated upper respiratory tract infection, croup, bronchiolitis, or pneumonia. It is not clear what role influenza type C plays in illness, but antibody studies reveal that virtually all children have experience with influenza C virus by the age of 10 years4 Data about uncomplicated influenza in children are limited.

The mucous membranes of the upper respiratory tract can show extensive destruction of ciliated epithelium. Secondary bacterial infection is a well-recog- nized complication, including sinusitis. Influenza infection uncomplicated by secondary bacterial infection shows marked desquamation of the tracheal epithelium as early as the first day after onset of symptoms. Repair of the epithelium begins in 3 to 5 days, with reappearance of cilia and mucous production within 15 days. Progression to viral pneumonia may occur if invasion of the respiratory epithelium is severe. Sudden worsening of clinical symptoms late in the course of influenza suggests bacterial infection and demands aggressive evaluation and paren- teral antibiotic therapy. Secondary bacterial infection of Staphylococcus aureus is of particular concern because the rapid progression of S. uuyeus pneumonia to large pleural effusions or empyema may cause significant respiratory compromi~e.~~

In the rare child dying of influenza pneumonia uncomplicated by bacterial superinfection pulmonary findings on microscopy include mucous and cellular debris plugging small bronchioles, necrosis of bronchiolar epithelium, and marked lymphocytic infiltration of the alveolar walls and interstitial lung tissue.

ADENOVIRUS

Adenovirus infection is associated with a variety of clinical syndromes including acute upper respiratory tract infection, pharyngitis, a pertussis-like syndrome, and pneumonia. Acute adenovirus upper respiratory tract infections are the most common manifestation in infants and children and are not clinically distinctive. They usually are caused by only 5 of the 37 plus serotypes of adenovirus. Adenovirus is one of the few respiratory viruses that grow well in the epithelium of the small intestine; therefore, adenovirus respiratory infections fre- quently are associated with diarrhea.

Adenoviruses infrequently cause pneumonia in children, but 7% to 9% of hospitalized children with acute pneumonia have adenovirus infe~t ion.~,~ Al- though uncommon, pneumonia from adenovirus is a serious infection with a mortality rate as high as 10%.

Adenovirus pneumonia produces characteristic microscopic changes with dense lymphatic infiltrates, destruction of the bronchial and bronchiolar epithelium, focal necrosis of mucous glands, hyaline membrane formation, and several


types of nuclear inclusion bodies. Residual airway damage from adenovirus may result in bronchiectasis, bronchiolitis obliterans, and, rarely, pulmonary fibrosis.

CYTOMEGALOVIRUS

Most cytomegalovirus (CMV) infections are inapparent, but they can cause a variety of clinical illnesses ranging from mild to fatal, including pneumonia. CMV infections are seen worldwide. Most humans have been infected by the time they reach adulthood. Approximately half of women of child-bearing age in the United States have serologic evidence of previous CMV infection. About 10% of infants in the United States who were not congenitally infected become infected in the first year of life.4 Pulmonary CMV infections are rare. When they occur, they typically manifest as interstitial pneumonitis and are seen primarily in immunocompromised hosts. CMV pneumonia can occur in newborns who have cytomegalic neonatal inclusion disease. Subacute CMV pneumonia with persistent fever and cough lasting for several months may occur. Patients with CMV pneumonia often shed virus in their urine and saliva.

MEASLES (RUBEOLA)

Measles virus induces inflammation throughout the respiratory tract. Respi- ratory complications such as pneumonia are common. Possibly because of the measles vaccine, measles pneumonia (Hecht's giant-cell pneumonia) is rare.4 It still occurs in patients with AIDS, in whom the respiratory infection may not be accompanied by a rash, and is often fatal. Measles infection may produce a primary pneumonia or contribute to a superimposed bacterial pneumonia. Broncho- pneumonia caused by secondarily invading bacteria such as Streptococcus pneumoniae is more frequent than viral pneumonia from measles. There is recent evidence that vitamin A deficiency contributes to the development of measles pneumonia. In underdeveloped countries, vitamin A supplements have decreased the death rate greatly.

VARICELLA ZOSTER PNEUMONIA

Varicella zoster, a human herpes virus, has the potential to cause pneumonia in childhood. In temperate climates such as the United States, 90% to 95% of individuals acquire varicella zoster virus in childhood. Few infected children develop pneumonia, although older children and adults are at greater risk. Varicella pneumonia is usually transient, resolving completely within 24 to 72 hours, but in severe cases, the interstitial pneumonitis progresses rapidly to cause respiratory f a i l~ re .~ Immunocompromised children face serious risks from varicella infections. The mortality rate has been documented to be as high as 7% without antiviral therapy. All varicella-related deaths occurred within 3 days after the diagnosis of varicella pneumonia.' Acyclovir is the drug of choice in varicella-zoster infections. Intravenous acyclovir is recommended immediately in patients who have signs of disseminated varicella-zoster infections such as pneumonia.1 Acyclovir does not interfere with induction of varicella-zoster-virus immunity.

A live, attenuated varicella vaccine, the first human herpes vaccine, was approved in 1995 in the United States. The vaccine has induced seroconversion rates of more than 85%. Persistent immunity has been documented in 94% to 100%


of recipients monitored for 1 to 6 years.16 This should have a major affect on preventing the complications of varicella-zoster virus pneumonia.

DIAGNOSTIC EVALUATION

Chest radiograph(s) in viral pneumonia characteristically show perihilar streaking. Increased interstitial markings, peribronchial cuffing or patchy bron- chopneumonia, and lobar consolidation also may occur. In children hospitalized with presumed viral pneumonia, up to 10% may have a normal chest radiograph. With RSV bronchiolitis, 50% show hyperexpansion, 50% to 80% peribronchial thickening or interstitial pneumonia, and 10% to 25% show segmental consolidation. Chest radiographs are typically useless in determining the actual viral agent causing the pneumonia; however, radiographic diagnosis of RSV is suggested by air-trapping and multilobar patchy shadowing, but no pattern is specific. Right upper-lobe collapse or consolidation has been reported in a high per- centage of patients with RSV (Fig. l).3

The peripheral white blood cell count is typically not useful in distinguishing viral from bacterial disease. A markedly elevated white blood cell count makes a viral illness less likely. In viral pneumonia, the white blood cell count may be normal or slightly elevated. Rapid viral diagnostic tests such as fluorescent antibody tests may be helpful in identifying the viral agent and are becoming more commonly available. In RSV, rapid and definitive diagnosis is based on detection of virus or viral antigens in respiratory secretions. Nasopharyngeal or throat swabs (or washings) are done to obtain mucus from the posterior pharyngeal cavity. Infants 1 to 4 months of age with RSV in their pharyngeal secretions also may have a concurrent bacteria or Chlamydia infection. Bacterial cultures of blood, counterimmunoelectrophoresis of urine, sputum or serum, and enzyme-linked immunosorbent assay are helpful in identifying the infecting agent(s).

Viral cultures, previously considered an academic exercise, are becoming increasingly more important in the hospital management of young infants with pneumonia. Antiviral agents such as the ribavarin or acyclovir can be considered therapeutic options when infecting agents are known.

Figure 1. Radiographic diagnosis of RSV is suggested by air-trapping and multilobar patchy shadowing.


DIFFERENTIAL DIAGNOSIS

In an individual case, the clinical determination of the cause of lower respiratory tract illness is difficult. Noninfectious conditions that may simulate pneumonia on chest radiograph or underlie acute pneumonia in children include phys- iologic causes such as a prominent thymus or underpenetrated chest radiograph; chronic pulmonary disease such as asthma or desquamated interstitial pneumonitis with recurrent aspiration; atelectasis, particularly caused by a foreign body; allergic alveolitis; damage caused by physical agents such as smoke inhalation; pulmonary infarction; or miscellaneous causes such as bronchogenic cysts. In patients in whom wheezing is prominent, asthma, airway obstruction caused by foreign body aspiration, acute bacterial, or viral tracheitis should be considered.

Additional consideration entering into the differential diagnosis includes the immunologic status of the host (whether compromised or normal), the age of the patient, the exposure history, and the season of the year. In certain settings the diagnosis of nonbacterial pneumonia may be made solely on the clinical presentation, season, and age. For example, a 3 month old presenting with low-grade fever, tachypnea, wheezing, and retractions during the winter in a community with known cases of RSV most likely has RSV bronchiolitis.

TREATMENT

There remain few effective treatments for viral pneumonia. Ribavirin, a syn- thetic analogue of guanosine6 approved for the treatment of viral pneumonia particularly caused by RSV with cost up to $1800 per day, has not proven to give the clinical results expected. It continues, however, to be considered in the management plans of compromised patients or in extremely ill patients in whom all other measures have failed. Because of the clouded clinical picture of viral versus bacterial pneumonia and the possibility of secondary invasion of bacterial during a primary viral infection, antibiotics continue to be a mainstay in management plans. The failure of response to antibiotics gives additional evidence of a viral cause. Amantadine and rimantadine have been shown to be effective in prophylaxis against influenza A but not influenza B infections. Acyclovir appears active against herpes simplex virus and varicella virus but has minimal activity against C W .

The treatment of viral pneumonia is primarily supportive. As with all pneumonias, close observation, monitoring of heart rate and oxygen saturation, oxygen supplementation, high humidity, bronchodilators, and chest physiotherapy are used as needed. Specific antiviral therapy should be considered in children with chronic lung disease or congenital heart disease.

COMPLICATIONS OF VIRAL PNEUMONIAS

Many children with asthma have a history of bronchiolitis in infancy. Recur- rent wheezing in 33% to 50% of children with typical RSV bronchiolitis in infancy has been documented, but the more serious complications as a result of residual airway damage include bronchiectasis, bronchiolitis obliterans, and, rarely, pulmonary fibrosis. The complications resulting from viral pneumonias most often are caused by severe destruction of the bronchial or respiratory epithelium. Focal necrosis and airway plugging caused by debris and mucus can interfere with ventilation and cause atelectasis, bronchospasm, apneic spells (in infants), and respiratory failure. An uncommon but severe complication of viral pneumonia is adult respiratory distress syndrome, which develops soon after clinical symptoms


are noted. Respiratory failure has been noted most commonly in cases of influenza and adenovirus pneumonia. Pulmonary support with mechanical ventilation or continued positive airway pressure is essential in patients with respiratory failure. The incidence of long-term complications after viral or mycoplasmal disease is unknown. Significant sequelae have been noted after adenoviral, influenza, and measles pneumonias. Evidence is accumulating to indicate that recurrent viral pulmonary infections in childhood, in association with environmental irritants (i.e., passive smoking), can lead to chronic lung disease in adult^.^

ATYPICAL PNEUMONIAS

There are many causes of pneumonia in children that cannot be classed as bacterial or viral. The most commonly discussed of these atypical pneumonias are those caused by the infectious agents of Mycoplasma pneumoniae and Chlamydia pneumoniae. Other infectious agents such as Chlamydia psittaci, Coxiella burnetii, Legionella, and fungi also can cause pneumonia in children but only infrequently. Noninfectious conditions that may simulate pneumonia must be differentiated from the atypical infectious pneumonias to facilitate appropriate therapy. Aspi- ration of gastric contents, baby powder or dust, hydrocarbon, or lipids can cause pneumonia. Hypersensitivity pneumonitis can produce an infiltrate that may be confused with infectious pneumonia.

In the primary care setting, the unusual causes of pneumonia always must be considered. This is especially true in the patient with an atypical history or who fails to respond to therapy. Most patients, however, will have bacterial, viral, mycoplasma, or chlamydia1 pneumonia. The remainder of this article assumes that we are not discussing the rare occurrences of a debilitated infant who has been fed mineral oil (lipoid pneumonia), a teenager who was siphoning gas (hydrocarbon aspiration), a child who works with pigeons (Chlamydia psittaci), a child who became ill after assisting in the delivery of a baby lamb (Coxiella burnetii), or the child with systemic lupus erythematosus who attended the American Legion Con- vention (Legionella pne~mophilia).~ Our discussion focuses on the two most common atypical pneumonias acquired by healthy children, mycoplasma and chlamydia pneumonia.

Characteristic features of different diseases serve only as a rough guide to form a best guess about an individuals diagnosis. The frustrating reality is that a patient with a typical presentation of viral pneumonia really may have a bacterial infection, and the same is true of patients with these two common atypical pathogens. It is wise to choose empiric therapy to cover all possible etiologic agents in a seriously ill child despite a high degree of suspicion for one etiologic agent. In the less ill patient, it still is useful to understand the differences in presentation among pathogens so that treatment might be more targeted to the likely organism. This is particularly important if we are to try to avoid the use of unnecessary antibiotics in the treatment of viral pneumonias.

MYCOPLASMA PNEUMONIAE

Organism

Mycoplasma pneumoniae is a pleomorphic organism that lacks a cell wall. It is not susceptible to p-lactams and other antibiotics that interfere with cell-wall syn- thesis. They have a filamentous end that allows them to attach to respiratory


endothelium by slipping between cilia. The resultant cilostasis from cell injury may be responsible for the prolonged paroxysmal cough that often occurs in M. pneumoniue infection.12

Epidemiology

M . pneumoniue infections can occur at any time of the year. Infection occurs through respiratory inhalation of large droplets. The disease is not highly com- municable. Spread through a family group may take weeks or months. The in- cubation period is probably 2 or more weeks. Epidemics can occur, especially among children in close contact, such as a daycare setting.

The rate of M . pneumoniue pneumonia is highest in children aged 5 to 9 years. Children aged 10 to 14 years continue to have high infection rates. In children younger than 5 years the rate of M. pneumonial infection is still twice that observed for adolescents and adults. Pneumonia from M . pneurnoniue is rare in infants younger than 6 months of age?

Clinical Picture

The clinical picture of M. pneumoniue infection is usually one of gradual onset of illness, often several days to weeks. Fever and dry cough occur, followed by malaise and headache. Cough is usually the most persistent symptom, lasting up to a month. The cough can become productive. The majority of patients will have abnormal findings of rales or wheezes on auscultation of the chest. Pharyngitis and bullous myringitis can occur, but the patient typically feels very ill with minimal clinical signs.

Laboratory

Chest roentgenographic findings vary, but an interstitial pattern is most common. The radiographic findings correlate poorly with clinical illnesses. The white blood cell count usually is less than 10 x 109 cells/L. The erythrocyte sedimen- tation rate may be elevated. M. pneumoniae cultures may take weeks to complete and are not widely available. There are no rapid specific tests for identification of M . pneumoniue. New, highly specific nonculture tests are under development and may prove helpful in the diagnosis of M . pneumoniae infections.

Measurement of an IgM autoantibody that agglutinates human erythrocytes at 4C (the cold agglutinin reaction) is a sensitive and specific means of diagnosing infection. Up to 75% of patients with M. pneumoniue are positive for cold agglu- tinins, and most cold agglutinin-positive pneumonias are caused by M. pneumoniue. The higher the titer is, the more severe the pulmonary involvement, and the more likely the infection is caused by M . pneumoniae. A bedside, cold agglutinin test can be helpful. A volume of blood equal to the amount of anticoagulant (usually less than 0.5 mL) is added to a standard prothrombin (blue-lopped) or he- matology (lavender-topped) tube. The test tube then is placed in ice, and the blood is observed for the presence of small specks of agglutination on the tube walls as the tube is rotated in a horizontal position. The agglutination should disappear with rewarming. A positive bedside agglutination test correlates with a titer of 1:64 or greater. Several specific serologic tests for M. pneumoniae exist, but their clinical use in acute infection in children is minimal (Fig. 2).*


Figure 2. Chest radiographic findings vary, but the interstitial pattern, as seen here, is most common.

Treatment

Therapy for M. pneumoniae pneumonia is largely empiric because of the lack of a rapid sensitive diagnostic test for the organism. Treatment does seem to pre- vent morbidity from the pneumonia even when given late in the course of the disease. Erythromycin and tetracycline are effective older antibiotics for the treatment of M. pneumoniae pneumonia. Tetracycline can lead to staining of the teeth in children younger than 8 years of age. Recently, azithromycin and clarithromycin have been recommended. The authors prefer azithromycin because of once daily dosing and short treatment course, which encourages excellent compliance. The older drugs tend to be less expensive. All these antibiotics are also effective against Chlamydia pneumoniae and most causes of bacterial pneumonia.

CHLAMYDIA PNEUMONIAE

Organism

Chlamydia pneumoniae is in the genus Chlamydia, which also contains the spe- cies c . psittaci and c. trachomatous. The organisms are obligate intracellular para- sites and all are capable of causing pneumonia in humans. C. pneumoniae (TWAR strain) first was described as a respiratory tract pathogen in 1986. It now is rec- ognized as an increasingly common cause of pneumonia in all age groups, causing up to 19% of community-acquired pneumonia.62

Epidemiology

C. pneumoniae appears to be a primary respiratory pathogen, spread presum- ably by respiratory inhalation of infected droplets. There is evidence of spread among household members and of frequent subclinical infection. C. pneumoniae, like M . pneumoniae, inhibits ciliary motion. C. pneumoniae organisms may not be the primary pathogen in a pneumonia but may allow other pathogens to invade.


Prolonged asymptomatic infection has been observed. C. pneumoniae has been im- plicated in reactive airway disease.

Clinical Picture

The spectrum of clinical presentations from C. pneumoniae are diverse. Most infections are probably mild and may even be asymptomatic. Cases of severe illnesses also have been described. The clinical picture may resemble infection from M . pneurnoniae with low-grade fever, dry cough, headache, and malaise. In infants, C. trachomatous infections along with other organisms cause the afebrile pneumonitis syndrome of infancy in which infants from 3 to 11 weeks of age present with persistent staccato cough, rales, and wheezing.I2

Laboratory

There are no characteristic radiographic findings. White blood cell count is usually less than 10 X 109 cells/L. Peripheral eosinophilia may be present. Or- ganisms can be cultured, preferably from the nasopharynx. Nasopharyngeal spec- imens also can be processed by fluorescent antibody staining with some success. Serology can be used to diagnose and to follow C. pneumoniae infection. Serologic antibody response may take weeks to develop. Children may fail to develop a measurable antibody response. Because of the lack of reliable, readily obtainable diagnostic testing for this infection, clinicians are forced to maintain a high level of suspicion for the disease and often to treat possible disease empirically.

Treatment

In studies, children have been shown to improve clinically with treatment, even if eradication of the organism is not shown. Erythromycin, tetracycline, ma- crolides, and quinolones appear effective against the organism. It is probably re- sistant to sulfonamide. The optimum dose and duration of treatment is not known. A prolonged treatment course (at least 2 weeks) may be needed. Azithromycin should be an effective drug against C. pneumoniae pneumonia if given as a 5-day course, followed after 5 days with a second 5-day course. A less expensive alter- native for older children would be that recommended by Hammerschlag; doxy- cycline, 100 mg/d divided in two doses for 21 days, or erythromycin, 500 mg/d divided in four doses also for 21 days. For young children, erythromycin suspen- sion, 500 mg/kg/d divided in four doses for 21 days, is recommended.12

CONCLUSION

Acute respiratory infections are the most common illnesses in the pediatric age group. Although pneumonia accounts for only 10% to 15% of all respiratory infections, it causes significant morbidity and mortality among children. Acute lower respiratory infection is associated most commonly with viruses, often with multiple pathogens but not with C. trachomatis after 4 months of age.I3 Severity of the disease, height of fever, radiographic findings, or characteristics of the cough or lung sounds do not reliably differentiate viral and atypical from bacterial pneu- m ~ n i a . l ~ , ~ It has been found that bacterial infection is a more common cause of pneumonia in pediatric outpatients than previously thought. The challenge for the


primary care provider is to make the correct diagnosis, to rule out associated serious conditions, and to begin rational treatment. It is also significant that concurrent infection occurs with equal frequency in inpatients and outpatients, indi- cating that concurrent viral and bacterial infection is not associated with unusually severe disease." In the absence of clinical and epidemiologic data suggesting viral or M . pneumoniae pneumonia, the severity of illness is probably the best guide to management; the child who is severely ill should receive antimicrobial treatment until recovery or until studies indicate this is not necessary. The child with mild pneumonia, at a time when a respiratory virus is causing disease common in other children in the community, may be observed without antibiotic therapy.'*

References

1. Boger KM: Ambulatory Pediatric Care: Pneumonia. Philadelphia, JB Lippincott, 1988, pp 683-689

2. British Thoracic Society Pneumonia Research Subcommittee Thorax: Prediction of aeti- ology at admission to hospital for pneumonia from the presenting clinical features.

3. Campbell PW, Hazinski TA Primary Pediatric Care, ed 2. St. Louis, Mosby Yearbook,

4. Denny FW, Clyde WA Jr: Medical progress: Acute lower respiratory tract infections in nonhospitalized children. J Pediatr 108(part 1):635-646,1986

5. Gleason WP, Taber LH, Frank AL, et al: Risk of primary infection and reinfection with respiratory syncytial virus. American Journal of Diseases in Children 140:543-546,1986

6. Greenberg SB: Lower respiratory tract infections: Viral pneumonia. Infect Dis Clin North Am 5:603-621,1991

7. Hammerschlag MR Atypical Pneumonias in Children. Advances in Pediatric Infectious Diseases. St. Louis, Mosby-Year Book, 1995, pp 1-39

8. Greenberg SB: Lower respiratory tract infections: Viral pneumonia. Infect Dis Clin North Am 5:603-626, 1991

9. Murphy TF, Henderson FW, Clyde WA Jr, et al: Pneumonia an eleven year study in a pediatric practice. Am J Epidemiol113:lZ-21, 1981

10. Orenstein DM: Aspiration pneumonias and gastrointestinal reflux-related respiratory disease. In Nelson WE: Textbook of Pediatrics, ed 15. Philadelphia, WB Saunders, 1996,

11. Paisley JW, Lauer BA, McIntosh K, et al: Pathogens associated with acute lower respi-

12. Pneumonia. In Nelson's Textbook of Pediatrics. pp 716721 13. Powell D A Mycoplasmal infections. In Nelson WE: Textbook of Pediatrics, ed 15. Phil-

14. Ruben FL: Postgraduate medicine. Viral Pneumonias 757-60,6344,1993 15. Schutze GE, Jacobs RF: Management of community-acquired bacterial pneumonia in

16. Turner RB, Lande AE, Chase P, et al: Pneumonia in pediatric outpatients: Cause and

18. Wright P: Influenza Viral Infections. pp 901-908

44:1031-1035,1989

1992, pp 1457-1459

pp 1213-1217

ratory tract infection in young children. Pediatr Infect Dis 3:14-19, 1984

adelphia, WB Saunders, 1996, pp 824-726

hospitalized children. Pediatr Infect Dis J 11:160-164, 1992

clinical manifestations. J Pediatr 111:194-200, 1987

Address reprint requests to Brenda A. Latham-Sadler, MD

Department of Family Medicine Bowman Gray School of Medicine

Medical Center Boulevard Winston-Salem, NC 27157

Documents

viral and atypical pneumonias.pdf