Severe Acute Respiratory Syndrome in Children

Lauren J. Stockman, MPH*†; Mehran S. Massoudi, PhD, MPH*; Rita Helfand, MD*; Dean Erdman, DrPH*; Alison M. Siwek, MPH*†; Larry J. Anderson, MD*; Umesh D. Parashar, MD, MPH*

Disclosures

Pediatr Infect Dis J. 2007;26(1):68-74. 

In This Article

Diagnosis

A comparison of clinical and epidemiologic features in laboratory-confirmed, probable and suspect SARS cases suggests that the clinical case definitions for SARS lacked both specificity and sensitivity among pediatric patients. In particular, the definition for suspect SARS appeared to have a low specificity. Patients with suspect SARS had a lower prevalence of constitutional symptoms such as chills or myalgia and lower rates of laboratory abnormalities than laboratory-confirmed and probable SARS cases. In addition, substantially fewer suspect cases reported histories of direct contact with a case of SARS compared with probable cases. Furthermore, many children classified as suspect SARS had an alternative diagnosis at discharge, such as viral fever, dengue fever or bronchitis.[15] The clinical case definitions for SARS also had limited sensitivity, and Leung et al determined that inclusion of lower respiratory tract symptoms in a case definition for SARS would have excluded 34% of pediatric patients who were found to be positive for SARS-CoV by laboratory confirmation but did not have these symptoms.[16]

Given the suboptimal predictive value of the clinical case definition for SARS, laboratory diagnosis is crucial for successful identification of SARS-CoV infection. Classic methods for identifying respiratory tract viruses, including cell culture and antigen detection, are not applicable for routine diagnosis of SARS-CoV because of their lack of sensitivity and potential safety risk to laboratory personnel. Laboratory diagnosis is best accomplished with sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) and serologic assays, but a clear understanding of the limitations of these tests is essential for their proper interpretation. In addition, experience with laboratory assays in pediatric patients is limited, and the information reported below primarily is based on experience in adult patients.

Validated and sensitive real time RT-PCR assays are available widely for SARS-CoV but may nevertheless be inadequate to detect the low levels of virus genome present during the first few days of illness. The sensitivity of RT-PCR can be improved by careful attention to specimen type and timing of collection. Blood/serum specimens collected within the first week after onset of illness during peak viremia may offer the best opportunity for early virus detection.[32,33] In infants, blood specimens collected by heel stick should provide adequate sample volume for testing. Lower respiratory tract specimens (eg, bronchoalveolar lavage, tracheal aspirates, sputum) collected in sufficient quantity and at different time points in the illness, but particularly between 1 and 2 weeks after onset of illness, have given the highest yield in adults.[17,34,35] In children, properly collected nasal aspirates or lavage may be more easily obtained and provide similar results; this should be evaluated. Studies also have shown that stool can be an excellent specimen for SARS diagnosis, particularly later in the illness, but data are lacking in children.[17,36,37]

Detection of antibodies to the SARS-CoV is the most reliable indicator of infection but has limited diagnostic value during the acute illness.[38] Serologic data from adults suggest that most persons seroconvert within 2-3 weeks after onset of illness.[17] However, some people do not develop detectable antibodies until >28 days after onset. Interpretation of serologic test results in infants may be complicated by the presence of maternal antibodies or lack of immune system maturity which could yield false positive or false negative results, respectively.

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