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Immunologic control measures may be key to reducing norovirus burden in HSCT recipients
Noroviruses represent the most common etiologic agents of acute gastroenteritis in all age populations.
The viruses are importantly spread by fecal-oral route, food, water and environmental surfaces, and the viruses can be spread by aerosol with vomiting.
The low inoculum required to cause infection — as well as resistance of noroviruses to harsh environmental conditions and cleaning procedures — makes the virus hazardous for transmission, whether it be on a cruise ship or in a hospital. It takes high concentrations of chlorine to kill the virus in the environment.
Herbert L. DuPont
In immunocompromised patients, due to failure of normal clearing mechanisms, the noroviruses can undergo mutations in amino acids that change the antigenicity and receptor usage and lead to presence of a diverse viral population in infected people.
All forms of immunosuppression show enhanced susceptibility to noroviruses. Genetics also appears to play a role in norovirus susceptibility in healthy hosts and presumably in the immunosupressed. Noroviruses are detected currently in reference or specialty laboratories by reverse transcription polymerase chain reaction, conventional or real time.
High rates of infection
Diarrhea due to all causes is common in transplantation; it is reported in up to 50% of autologous and 80% of allogeneic hematopoietic stem cell transplantations (HSCT).
Important causes of diarrhea include conditioning therapy, graft-versus-host disease (GVHD), drugs and enteric infection. Although other forms of enteric infection — such as Clostridium difficile infection — occur more commonly, norovirus infection occurs with uncertain frequency in HSCT units and in other settings in which immunosuppressed patients are housed. In some studies, norovirus infection rates have been as high as 18% in patients who undergo allogeneic HSCT.
Norovirus infection often develops with intensified immunosuppression given for suspected GVHD. In some settings, norovirus infection rates have reached such high levels that units have had to be closed. Symptoms of norovirus infection in these settings can be persistent, ranging from a month to multiple years, with prolonged excretion of the infecting organism. Norovirus infection may influence clinical outcome, including weight loss, renal failure and mortality.
Immunologic control
In a hospital setting, multiple strains of norovirus can be found, suggesting that most cases are not part of a nosocomial outbreak.
Recovery of T-cell function in patients who undergo HSCT is associated with immune reconstitution, emphasizing the need to decrease levels of immunosuppression to control norovirus infection.
Infection control methods are important for reducing occurrence of norovirus infection. Personal hygiene and hand-washing must be emphasized. Careful environmental surface cleaning should be performed regularly in units that house immunosuppressed people.
More study is needed to determine the importance of norovirus infection in the various groups of immunosuppressed patients. It is unknown if screening patients before stem cell transplantation or before administering immunosuppressive drugs would be important as part of efforts to diagnose infections early.
More rapid and sensitive diagnostic tools and effective therapeutic agents should be identified. Antinorovirus-specific antibody preparations should be produced and evaluated as a therapeutic modality.
Norovirus vaccines, which are in the pipeline, should be evaluated in patients who are immunocompromised. Ultimately, immunologic control measures may be the most important measures in reducing the burden of norovirus infection in immunocompromised patient populations until effective antiviral drugs become available.
References:
Roddie C. Clin Infect Dis. 2009;49:1061-1068.
Saif MA. Pediatr Transplant. 2011;15:505-509.
For more information:
Herbert L. DuPont, MD, MACP, is clinical professor of medicine and vice chair of the department of medicine section of infectious diseases at Baylor College of Medicine. He also is chief of medicine at St. Luke’s Episcopal Hospital in Houston. He can be reached at St. Luke’s Episcopal Hospital, 6720 Bertner, MC1-164, Houston, TX 77030.
Disclosure: DuPont reports no relevant financial disclosures.