For immunocompromised people, every cough and sniffle poses a threat. Respiratory viruses that are harmless to most of us can lead to dangerous complications in patients with weakened immune systems. VIDI research associate Dr. Angela Campbell wants to understand the course and natural history of respiratory virus infections, an effort that she hopes will eventually lead to better treatments of these diseases. In initial studies among stem cell transplant patients, she has found that the respiratory virus parainfluenza is much more common than previously thought.
These studies will be useful not just for the immunocompromised, but for anyone who suffers from one of the many common human respiratory viruses. However, immunocompromised people offer an opportunity to study the most dramatic effects of these viruses.
“The goal is not to apply our findings only to the immunocompromised population,” Campbell said. “But if anyone is going to get a severe disease from these viruses, it’s them.”
Campbell’s current studies focus on patients who have received allogeneic hematopoietic cell transplants (HCTs), which are transplants of bone marrow-derived stem cells from a donor. HCT recipients are often leukemia or myeloma patients, but a variety of childhood and adult diseases may require an HCT.
Since she was awarded a K23 grant and began her current position at the Center two years ago, Campbell’s main focus has been on parainfluenza viruses, which are one of the causes of the common cold. Parainfluenza infection can also lead to croup, bronchitis or pneumonia in healthy people as well as to more dangerous lower respiratory infections in young children and immunocompromised individuals. Approximately 20-30 percent of HCT patients who are infected with parainfluenza and show symptoms may progress to pneumonia, Campbell said.
Drugs are available for other common respiratory viruses, such as influenza and respiratory syncytial virus (RSV), but not for parainfluenza, Campbell said. “It’s really the next big player in terms of respiratory virus incidence and severity of disease,” she said.
To learn more about the virus, Campbell is a co-investigator for a large study run by VIDI member Dr. Michael Boeckh to examine the course of disease progression of a number of respiratory viruses in HCT patients. Until 2007, Campbell was an infectious disease fellow at the Center, training under the co-mentorship of Boeckh and VIDI associate investigator Dr. Janet Englund, an experience that has allowed her to be involved with the HCT study since its inception in 2005. The HCT study enrolls transplant patients from the SCCA who donate nasal wash and blood samples before transplant, then weekly for three months following the transplant. If the patient stays healthy, samples are then collected every three months up to a year after transplant. If the patient develops a respiratory illness, samples are collected from the patient more frequently until his or her recovery is complete.
These studies are unique in that samples are collected from patients with and without cold-like symptoms. Thus, the scientists can learn more about the prevalence of respiratory viruses in the HCT population and the frequency of asymptomatic respiratory viral infections. Importantly, this may potentially enable the clinicians to monitor or treat an infected patient before the disease progresses very far. In a pilot study of respiratory viruses among HCT recipients, Campbell and her colleagues found that parainfluenza viruses caused the most frequent infections of all the respiratory viruses they evaluated, with a cumulative incidence estimate of 18 percent at three months after transplantation.
Campbell is also interested in developing a rapid diagnostic method for respiratory virus infections and in knowing how these pathogens are transmitted. To that end, she and her colleagues are working on ways for patients to collect their own upper respiratory samples, a method which would enable frequent sample collection from both healthy and immunocompromised people.
Traditional nasal washes can be unpleasant for study participants, Campbell said. She hopes the self collection technique, which involves squirting a small amount of saline into the nose and then exhaling onto a soft foam swab, will remove some of the barriers to the sample collection process needed to study virus shedding and transmission. Data from self collection studies could potentially shed light on viral persistence, the prevalence of asymptomatic infections, and, if multiple family members participate in the studies, the transmission patterns of viruses. Self collection could also be useful for surveillance of respiratory virus infections in the setting of an outbreak
Campbell conducted a study using nearly 200 paired samples from immunocompetent participants with new-onset respiratory illness to compare virus detection in staff-collected nasal washes and self-collected swabs and found that the two techniques were equivalent in sensitivity and specificity of virus detection. Her poster presentation on this study won a Joint Meeting Program Committee Award in the area of Clinical Microbiology and Diagnosis at the 2008 Interscience Conference on Antimicrobial Agents and Chemotherapy/Infectious Diseases Society of America meeting.
Campbell is a pediatric infectious disease specialist and is interested in children’s diseases. She is conducting a small study on the feasibility of self collection and mailing of samples from children with cystic fibrosis. Self-collection would be a useful tool to study respiratory illnesses, Campbell said, because these patients are usually at home and the need to travel for a medical visit can lead to delayed or missed sample collection for diagnostic testing.
Eventually, Campbell would like to translate her studies on self collection into better methods for rapid diagnosis of infectious diseases. Such approaches could potentially be used in resource poor settings, she said. She also hopes her studies on respiratory viruses in immunocompromised people will ultimately lead to development of better preventive strategies and treatments for these infections.
“The whole point of learning how these viruses affect people is to create an intervention to try to stop them from causing severe disease,” Campbell said.