Indian Pediatrics 2002; 39:259-266
Atypical Pneumonia in Children
The term atypical pneumonia denotes opposite of typical pneumonia. This term was first used in 1930s, for a group of conditions, which unlike a typical pneumonia are characterized by an insidious onset, and interstitial inflammation of the lungs, showing patchy infiltrates on chest radiographs. In general, this group of disorders pursues a much less virulent course and is associated with lesser mortality than patients with typical pneumonia. Peripheral leukocytosis is less common in this group of patients and routine cultures fail to reveal a microbial cause(1). Mycoplasma pneumoniae, Chlamydia tracho-matis, Chlamydia pneumoniae and Legionella are the organisms responsible for most of the cases of atypical pneumonia in children. A definitive diagnosis is difficult in these patients and this group of organisms do not respond to antibiotics commonly used for community acquired pneumonia. Therefore, while treating pneumonia, one needs to consider these organisms in presence of atypical features. The present communication presents a brief review of pneumonia caused by this group of organisms.
Mycoplasma pneumonia is caused by Mycoplasma pneumoniae (M. pneumoniae), pleuro-pneumonia like organisms belonging to the distinctive genus of mycoplasma. Outbreaks of this pneumonia can occur in any season, but have been noted more frequently during the months of fall. Few authors have reported positive serology for M. pneumoniae in as high as 30% of patients with acute respiratory tract infections(2). This infection spreads via the droplet route from the close contacts e.g., family units and dormitory setting. The infection is highly communicable affecting 75% of the susceptible household contacts. Incubation period is about 3 weeks, so course of the family outbreaks can run in months. All the age groups can be affected; however, the peak age for mycoplasma pneumonia is 6 to 18 years.
The organism can give rise to mild upper respiratory tract infection, bronchitis, bronchiolitis and bronchopneumonia. Usually the disease starts as influenza like syndrome with the predominant symptoms being fever, malaise, headache, scratchy sore throat and cough. The temperature rarely exceeds 38.5ºC. The symptoms in mycoplasma infection are much worse than what the physical signs will suggest. Examination of the chest usually reveals crepitations, localized wheeze and small areas of dullness to percussion over atelectatic areas or fluid collection. Various non respiratory features of mycoplasma infection are skin rashes, arthral-gia, hemolytic anemia, muscle tenderness and central nervous system invovlement including acute cerebritis, aseptic meningitis, cerebellar ataxia, transverse myelitis and Guillaine barre syndrome(3).
Generally mycoplasma pneumonia is a benign and self-limiting process, in which the treatment is needed mainly to reduce the morbidity. Total illness is usually sub-acute extending for a month or more. As most of the patients remain ambulatory, mycoplasma pneumonia is best known as walking pneumonia. However, it is well documented that with severe infections, admission may be required for oxygen and respiratory support. Kurashi et al from Saudi Arabia have reported that 129 out of 351 proven cases of patients of age group 13-20 years admitted with pneumonia were due to mycoplasma infection suggesting that mycoplasma pneumonia is not always an ambulatory pneumonia(4). M. pneumoniae reduces mucocilliary clearing by causing damage to the epithelial cells. This can predispose to super-added infection with organisms like H. influenzae(5). Toikka et al. have also reported mixed infection with S. pneumoniae and M. pneumoniae as cause for community acquired pneumonia(6). It is not very common to have long-term sequelae after mycoplasma infection. However, residual pleural abnormality and delayed mucocilliary clearance have been reported after mycoplasma infection.
Radiographic changes in mycoplasma pneumonia are not specific and can mimic a large variety of other conditions. Most commonly seen findings are broncho-pneumonic infiltrates, generally in one of the lower lobes. Small areas of segmental or sub-segmental atelectasis are also common. Rarely, enlargement of hilar lymph nodes, segmental consolidation or pleural effusion can be seen in chest radiograph. Pleural effusion has been reported in 20% cases with this infection.
Table I__ Various Tests Available for Diagnosis of M. pneumoniae
Various tests available for diagnosis of M. pneumoniae infection are enlisted in Table I(7-9). Since it is difficult to culture the organism, laboratory tests based on culture alone do not help much in planning chemotherapy. Therefore various authors have developed rapid serolgoical methods for detection of IgM antibodies as an indicator of recent infection. Ramamoorthi et al. from Madras have shown seropositivity by agglu-tination test in 31.5% of children with lower respiratory tract infections(10). Chaudhary et al. have shown sensitivity of indirect immunofluorescence test for antigen detec-tion from throat swabs as 85.7% and specificity of 93.3%(11). Mathai et al. from Tamilnadu have shown that 30% children with acute respiratory tract infections had IgM antibodies by particle agglutination test with ELISA(2). However, this study had been conducted in a selected group of patients over a very small period of time. Pandey et al. from Delhi have shown culture positivity in 10%, antigen detection in throat swab by indirect immunofluorescence test in 22.8% and demonstration of IgM antibody in serum by particle agglutination testing in 24.2% children of less than 5 years of age suffering from acute respiratory tract infections(12).
Chlamydia are obligate intracellular para-sites, now regarded as Gram negative bacteria, contain DNA and RNA, contain cell wall material and share common antigens. Genus chlamydia contains 3 species named Chlamy-dia pneumoniae (C. pneumoniae), Chlamydia trachomatis (C. trachomatis) and Chlamydia psitacci.
C. trachomatis causes illness during the first six months of life. It is responsible for about one third cases of pneumonia during this age group.
The infant usually acquires the organism during passage through the birth canal from chronically infected mothers. Usual age of presentation is at 3 weeks to 3 months of life, but sometimes patient presents at even younger age. Muhe et al. have reported C. trachomatis in 15.8% infants younger than 3 months of age, who had pneumonia, sepsis and meningitis(13). Similarly Colarizi et al. have reported that C. trachomatis is not an infrequent cause of respiratory distress even in early childhood. They have shown that 8/103 preterm neonates were positive for C. trachomatis as early as within 24 hours of life(14).
The disease usually starts with upper respiratory tract signs like nasal obstruction with or without discharge, which gradually worsen to cough and tachypnea. Cough usually occurs as staccato paroxysms that may be followed by vomiting or periods of apnea. The characteristic feature of this infection is that inspite of extensive pneumonia, the infant almost always remains afebrile. In 50% patients, presence or history of conjunctivitis can be elicited. Some infants also have secretory otitis media. Auscultation of the chest often reveals irregularly distributed crepitations and evidence of symmetrical hyper-expansion. Infants with this infection are prone to develop reactive airway disease in later life. Chest radiograph reveals symmetrically distributed interstitial type infiltrates along with scattered patches of airless lung and a narrowed upper mediastinal silhouette. Arterial blood gas analysis usually shows PaO2 values in range of 50-60 mm Hg, whereas PaCO2 values are usually within normal limits. Blood examination often shows absolute eosinophilia. Hypergamma-globuli-nemia is a common finding in patients having Chlamydia trachomatis pneumonia. Culture of the organism from nasopharyngeal secre-tions remains the gold standard for the diagnosis of C. trachomatis infection. Ligase chain reaction, direct immunoflourescence test, micro-immunofluorescence test and ELISA are the other tests used for diagnosis of C. trachomatis(15-16).
It is a recently described chlamydial species of clinical significance in older children and adults. It was previously known as TWAR agent and was recognized as a respiratory pathogen in 1980s. The name TWAR was taken from the laboratory designation of the first two isolates, TW-183 and AR-39(17). C. pneumoniae has been reported in 3.6% and 2.7% of children with lower respiratory tract infections (18,19). From India, this figure has been reported to be as high as 6.4%. However, all these studies have used different methods for diagnosis of this infection(11,18,19).
Infection with C. pneumoniae can present as endemic as well as epidemic form. An epidemic of pertussis like illness with C. pneumoniae in adolescents has been reported(20). Mode of transmission is person-to-person spread. In children, attack rate with this infection is about 5% and increases to 20% in adolescents.
This infection has been associated with pharyngitis, sinusitis and bronchitis. Incuba-tion period is 15-23 days. The disease starts as hoarseness, pharyngitis, fever, non-productive cough, non-pleuritic chest pain, headache, and malaise. Initially, chest examination may be normal. Thom et al. have reported that as compared to M. pneumoniae, patients with C. pneumoniae were less likely to have temperature greater than 37.8ºC, but were more likely to present with sore throat or hoarseness and the mean number of days from onset of symptoms until enrolment was longer in patients with C. pneumoniae infections than in those with M. pneumoniae suggesting a more gradual onset of disease(21).
As pneumonia progresses, rales appear in the chest, C. penumoniae is known to be associated with hyper-reactive airway. Infec-tion with C. pneumoniae can trigger acute epidosde of wheezing in children with asthma. Emre et al. have isolated C. pneumoniae from 11% of children with wheezing(22). C. pneumoniae has been classically known to cause a mild atypical pneumonia, which can be treated on an outpatient basis. However Kauppinen et al. have shown that C. pneumoniae is capable of causing pneumonia severe enough to require admission to hospital even in relatively young patients(23).
Chest radiograph usually shows unilateral infiltrate, which progresses to bilateral involvement with mixed pattern of interstitial and alveolar infiltrates. Small to medium sized pleural effusions are known to occur. Isolation of the organism from respiratory secretions remains the gold standard for diagnosis. However, being a fastidious organism, success of the culture depends on the type of the culture medium used. Complement fixation test, enzyme immuno-assays and immunoflourescence test require four fold rise to be of significance. Ben-Yakkov et al. have used micro-immunofluorescence assay for detection of antibodies to C. pneumoniae(24). Polymerase chain reaction in respiratory secretions is highly sensitive method. Hagiwara et al. have reported effectivity of this test in his patients(20). Chaudhary et al. from Delhi have used indirect solid phase enzyme immuno-assay for detection of IgG antibodies to determine the prevalence of C. pneumoniae and have shown sensitivity of this test as 88.8% and specificity of 75.8%(11).
The family Legionellaceae comprises of 41 species with 63 sero groups, of which the species L. pneumophilia causes 80-90% of human infections with this family(25). Legionnaires’ disease is a disease of elderly people; however, few cases have been reported in children. Legionella infection was first of all recognized in 1976. Bacteria of genus Legionellae are aerobic, thin Gram-negative bacilli that do not grow in routinely used microbiological media. Amongst various species of Legionella family, L. pneumophilia is the most common causing pneumonia. L. pneumophilia can occur as sporadic infections or in outbreaks, which are usually associated with hospitals, hotels and office buildings. Various modes of transmission of legionella are aerosolization, aspiration and direct instillation into the lung during respiratory tract manipulations(26). Nosocomial trans-mission is known in neonates and children with immuno-suppression or underlying pulmonary disease. Potential risk factors for legionella pneumonia in neonates are pre-maturity, congenital heart disease, broncho-pulmonary dysplasia and prolonged cortico-steroid therapy(27,28).
Incubation period is 2 to 10 days. The course and prognosis of this disease resembles that of pneumococcal pneumonia more than that of pneumonia due to other atypical pathogens.
The disease usually starts as mild cough, malaise, fatigue, and anorexia. Child can have chest pain, gastrointestinal symptoms and encephalopathy. Nausea, vomiting and abdominal pain are present in 10-20% of patients and diarrhea is seen in as high as 25-50% of patients. Various extra pulmonary manifestations in legionellosis are renal failure, myocarditis, pericarditis, endocarditis, peritonitis, pyelonephritis, cellulitis and pancreatitis. Extra pulmonary manifestations are especially documented in immuno-suppressed patients(26). Radiographic find-ings are non-specific, consisting of pulmonary infiltrates. To begin with, there are usually patchy alveolar infiltrates involving one lobe, which ultimately progresses to lobar or multilobar consolidation(29). Pleural effusion can be seen in one third of cases. Nodular opacities and cavitations can be seen in immuno-compromised patients.
Various abnormalities noted in Legionella pneumonia are hyponatremia, thrombo-cytopenia, hematuria, and abnormal liver function tests. Culture of the respiratory secretions is most specific and most sensitive method for the diagnosis of legionella infec-tion. Antibody detection of acute phase and convalescent sera by indirect immuno-fluorescence antibody test is mainly of epidemiological interest. Antigen detection in urine by ELISA or by solid phase radioimmunoassay is easy, rapid and highly specific and sensitive method(27). PCR of serum has been used for identification of legionella(30). Bahl et al. from Delhi have used culture sensitivity, direct fluorescence and ELISA for detection of legionella in adult patients with lower respiratory tract infections(31). Chaudhary et al. have reported the role of ELISA for detection of L. pneumophilia(32). However, no such study is available in pediatric population from India.
Treatment of atypical pneumonia
Macrolides are the treatment of choice for atypical pneumonia. Newer macrolides have advantage over eryhromycin that they have better tissue penetration and bioavailability, in addition they have decreased incidence of gastrointestinal side effects. Azithromycin has the advantage of once daily administration and shorter therapy course, whereas clarithromycin and roxithromycin are used only in twice-daily dosage schedule. Newer macrolides, especially clarithromycin have improved activity compared with that of erythromycin against staphylococcal, strepto-coccal as well as Hemophilus species. Therefore, macrolides can be considered as the drug of choice in the management of community acquired pneumonia(33).
Many authors have used quinolones effectively as empiric therapy for community acquired pneumonia in adults; however, not much literature is available for children. They are effective against wide range of pathogens including Gram-positive organisms like S. pneumoniae, H. influenzae and atypical organisms like C. pneumoniae and M. pneumoniae. Therefore, they have potential to be recommended as drug of choice for community acquired pneumonia. Newer quinolones like levofloxacillin, grepafloxa-cillin have also shown good in vitro activity against various organisms causing community acquired pneumonia and they have prolonged serum half-lives, thus permitting once daily dosage schedule. However, most of the newer quinolones are not available in India. Till more prospective studies are available in children, quinolones can be reserved for infections resistant to macrolides(34-36).
Other antibiotics useful in atypical pneumonia are shown in Table II. The duration of therapy for M. pneumoniae is 10-14 days; however, azithromycin has been used for 3-5 days. Chlamydial pneumonia needs treatment for 21 days. For legionella infection, treatment needs to be continued for 10-14 days in immunocompetent patients and 21 days in immunosuppressed patients(3,26,37). Supportive treatment in form of oxygen, intravenous fluids, chest physiotherapy is similar to any other pneumonia.
To summarize, atypical organisms are responsible for sizeable number of children with community-acquired pneumonia. This pneumonia can be severe enough to need admission in the hospital. Macrolides are the drugs, commonly used for this pneumonia.
Contributors: MSa reviewed the literature and drafted the paper. MSi critically revised the manuscript. Both will act as the guarantor for the manuscript.
Competing interests: None stated.