Risk factors for severe RSV infection in immunocompromised children

Feb 4 2008

St. Jude Children's Research Hospital investigators and collaborators have shown how to predict if a child who is infected with respiratory syncytial virus (RSV) while being treated for cancer or another catastrophic disease is at high risk for developing severe infection. The finding will help clinicians improve guidelines for managing these infected children.

RSV is a common cause of pneumonia among infants, children and adults during winter, frequently causing fever, runny nose and coughs. It can be much more severe in patients who are undergoing cancer treatments and whose immune systems are suppressed. In these patients, the virus can move into the deep lung, causing pneumonia and other respiratory problems that can be fatal. However, it is difficult to predict which infected patient is likely to develop a serious lower respiratory tract illness and which one will continue to simply have a mild runny nose and cough.

The St. Jude team and collaborators found that if these children are under 2 years old and have very low levels of immune system cells in their blood called lymphocytes, they are at high risk for the RSV infection to become serious by moving into the lung. Such infections are especially dangerous because they can be fatal in some immunocompromised children, and there is no standard effective treatment for these infections, the researchers said. A report on the retrospective findings appears in the February issue of the journal "Pediatrics."

The new information is important because it helps identify children who are most at risk for severe disease using easily available clinical information," said Aditya Gaur, M.D., assistant member of the St. Jude Department of Infectious Diseases and the paper's senior author. "This narrows down the patient population who needs to be considered for antiviral therapy, which is costly and often inconvenient to receive from a child's perspective. For example, one treatment for RSV infection is to have the child breathe an aerosolized form of the antiviral drug ribavirin for 12 to 18 hours, which is tough for the child and the parent."

The findings of this study require confirmation in prospective studies, Gaur said. Results of the study also help define which children should receive medications that can help prevent RSV infection.

Another significant finding was that--unlike some previous reports in immunocompromised adults with RSV--neutropenia is not a risk factor for lower respiratory track infection, Gaur said. Neutropenia is an abnormally low level of neutrophils, immune system cells that engulf and digest germs.

"This finding is important because with cancer patients, clinicians are used to identifying those at risk for bacterial and fungal infections based on a patient having neutropenia," Gaur said. This study shows that for RSV, which is a viral infection, lymphopenia and not neutropenia is what identifies children at risk.

Previous studies have shown that lower respiratory track infection, is more common in children whose immune system is suppressed, who are receiving chemotherapy or who have received a hematopoietic stem cell transplant (HSCT). However, while some studies report that lower respiratory track infection, due to RSV is fatal in 50 to 100 percent of infected adults, there is little information about this type of infection in immunocompromised children. "We decided to analyze the course of RSV infection in children being treated for cancer to identify factors that could help us predict which ones were at highest risk for severe disease or death due to a lower respiratory tract infection with this virus," Gaur said. HSCT is the transplantation of special cells from the blood or bone marrow that can give rise to all the blood cells of the body (red and white cells and platelets).

The St. Jude team studied clinical and laboratory information from the records of 58 patients who had tested positive for RSV infection. Among these children, 23 (40 percent) had acute lymphoblastic leukemia, 11 (19 percent) had solid tumors and 24 patients (41 percent) had acute myeloid leukemia (AML), severe combined immunodeficiency syndrome (SCIDS), or had undergone bone marrow transplantation. RSV disease in these infected children was classified as upper respiratory track infection only or lower respiratory tract infection; and children with both upper and lower respiratory track infections, were defined as having lower respiratory track infection.

Overall, 16 (28 percent) of these children developed lower respiratory track infection, due to RSV. The frequency of this type of infection was highest (42 percent) in patients who had undergone HSCT or who had AML or SCIDS. Five patients (31 percent) with LRTI died, an overall mortality rate of 8.6 percent. All deaths occurred in lower respiratory track infection patients who were severely immunocompromised from their cancer, from chemotherapy or from the HSCT.

Other researchers include C. M. El Saleeby (formerly of St. Jude and now at MassGeneral Hospital for Children, Boston), G. W. Somes (Department of Preventive Medicine, University of Tennessee, Memphis) and J.P. DeVincenzo (Le Bonheur Children's Medical Center and University of Tennessee, Memphis).