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Prevention of cytomegalovirus infection after marrow transplantation
1Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Abstract:
Primary infection with cytomegalovirus (CMV) in seronegative patients is acquired most commonly from blood products or marrow taken from seropositive donors, whereas recurrent infection in seropositive patients appears to be derived predominantly from reactivation of latent endogenous virus. Not all infected patients develop symptomatic CMV disease; the factors that determine severity of infection and recovery are not yet fully defined. The epidemiology of CMV infection indicates that primary infection is preventable by use of seronegative blood products, including marrow. Such techniques should be implemented immediately. Leukocyte depletion of blood products is a potential alternative, but both efficacy and logistics of implementation require further study in patients who need large quantities of blood products. The efficacy of passive immunoprophylaxis with immunoglobulins remains uncertain, and this modality cannot be recommended until additional data are available. Among seropositive patients, antiviral agents may be used to suppress CMV infection until periods of improved immunocompetence. Although not effective for the treatment of established CMV infection, intravenous acyclovir significantly reduced the probability of CMV infection and disease and improved survival in a controlled trial. The newer antiviral agents ganciclovir and foscarnet should provide better protection, although the marrow toxicity of ganciclovir is problematic. Future directions will include attempts to restore specific immune responses with subunit or recombinant vaccines and adoptive immunotherapy with CMV-specific effector cells generated in vitro.
Insights
Preventing primary cytomegalovirus (CMV) infection in seronegative patients is possible using CMV-seronegative blood products. Antiviral agents can suppress CMV in seropositive patients, but further research is needed for optimal strategies.
Area of Science:
- Infectious Diseases
- Immunology
- Hematology
Background:
- Primary cytomegalovirus (CMV) infection is often transmitted via blood products or marrow from infected donors.
- Recurrent CMV infections typically result from reactivation of latent virus in previously infected individuals.
- Symptomatic CMV disease varies, and factors influencing severity and recovery remain unclear.
Purpose of the Study:
- To review the epidemiology of cytomegalovirus (CMV) infection.
- To discuss strategies for preventing primary CMV infection.
- To evaluate current and future therapeutic approaches for CMV infection and disease.
Main Methods:
- Review of epidemiological data on CMV transmission and reactivation.
- Analysis of preventive strategies, including seronegative blood products and leukocyte depletion.
- Evaluation of antiviral therapies (acyclovir, ganciclovir, foscarnet) and immunoprophylaxis.
- Discussion of future research directions, including vaccines and immunotherapy.
Main Results:
- Primary CMV infection is preventable through the use of seronegative blood products and marrow.
- Leukocyte depletion shows potential but requires further study for efficacy and logistics.
- Intravenous acyclovir reduced CMV infection probability and improved survival but is not effective for established disease.
- Newer antivirals like ganciclovir and foscarnet may offer better protection, despite ganciclovir's marrow toxicity.
Conclusions:
- Immediate implementation of seronegative blood product strategies is recommended to prevent primary CMV infection.
- Antiviral agents can suppress CMV in immunocompromised patients, with newer agents showing promise.
- Further research is essential for optimizing CMV prevention and treatment, including exploring vaccines and adoptive immunotherapy.