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Questions and Answers
What is a defining characteristic of herpesviruses, including cytomegalovirus (CMV)?
What is a defining characteristic of herpesviruses, including cytomegalovirus (CMV)?
Which symptom is most commonly associated with congenital CMV infection in newborns?
Which symptom is most commonly associated with congenital CMV infection in newborns?
Which component of the immune response is primarily activated in individuals infected with CMV?
Which component of the immune response is primarily activated in individuals infected with CMV?
What does primary viremia of CMV indicate in the infection cycle?
What does primary viremia of CMV indicate in the infection cycle?
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In what type of cells does CMV establish latent infections?
In what type of cells does CMV establish latent infections?
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What factor is considered a key driver of CMV reactivation from latency?
What factor is considered a key driver of CMV reactivation from latency?
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Which structure is produced as a characteristic cytopathogenic effect (CPE) of CMV infection?
Which structure is produced as a characteristic cytopathogenic effect (CPE) of CMV infection?
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What is the global prevalence of cytomegalovirus (CMV) in developing countries?
What is the global prevalence of cytomegalovirus (CMV) in developing countries?
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What is a common life-threatening complication of HCMV in transplant recipients?
What is a common life-threatening complication of HCMV in transplant recipients?
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How does HCMV primarily evade the immune response?
How does HCMV primarily evade the immune response?
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Which therapeutic option is effective in preventing the replication of HCMV in solid organ graft patients?
Which therapeutic option is effective in preventing the replication of HCMV in solid organ graft patients?
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What factor contributes to the challenges in developing an effective HCMV vaccine?
What factor contributes to the challenges in developing an effective HCMV vaccine?
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What is the role of immune globulin (CytoGam) in the management of HCMV?
What is the role of immune globulin (CytoGam) in the management of HCMV?
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Which cellular process is inhibited by HCMV to downregulate the immune response?
Which cellular process is inhibited by HCMV to downregulate the immune response?
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What is a characteristic of HCMV infection in immunocompromised patients?
What is a characteristic of HCMV infection in immunocompromised patients?
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What is the major mode of HCMV transmission in congenital infections?
What is the major mode of HCMV transmission in congenital infections?
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What is the most common manifestation of Cytomegalovirus (CMV) disease in immunocompromised patients?
What is the most common manifestation of Cytomegalovirus (CMV) disease in immunocompromised patients?
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Which of the following is a common neonatal manifestation of congenital CMV infection?
Which of the following is a common neonatal manifestation of congenital CMV infection?
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What best describes the immune response to primary CMV infection in patients post-renal transplant?
What best describes the immune response to primary CMV infection in patients post-renal transplant?
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How does CMV typically behave in the context of an immunocompetent host?
How does CMV typically behave in the context of an immunocompetent host?
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What characterizes the CMV infection cycle in immunocompromised individuals?
What characterizes the CMV infection cycle in immunocompromised individuals?
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Which statement best describes CMV's immune evasion mechanisms?
Which statement best describes CMV's immune evasion mechanisms?
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What are potential consequences of CMV reactivation in transplant recipients?
What are potential consequences of CMV reactivation in transplant recipients?
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What role do co-infections play in CMV disease progression in immunocompromised patients?
What role do co-infections play in CMV disease progression in immunocompromised patients?
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Which of the following is NOT associated with congenital CMV infection in neonates?
Which of the following is NOT associated with congenital CMV infection in neonates?
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What is a significant determinant of disease outcome in individuals with primary HCMV infection?
What is a significant determinant of disease outcome in individuals with primary HCMV infection?
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Study Notes
Cytomegalovirus (CMV) Disease
- CMV infection in immunocompetent individuals is typically asymptomatic or causes mononucleosis.
- CMV is a common cause of congenital infection.
- CMV is a major cause of morbidity and mortality in immunocompromised patients.
- CMV commonly affects AIDS and transplant patients.
CMV in Immunocompetent Patients
- Most CMV infections in immunocompetent individuals are asymptomatic, but can result in a mild infectious mononucleosis syndrome.
- The immune response in immunocompetent individuals typically controls CMV and prevents high viral loads needed to cause end-organ disease.
CMV Congenital Infections
- Primary or reactivation of CMV infection in pregnant women can lead to congenital CMV infection.
- CMV can be transmitted via contact with infected urine and saliva, sexual contact, blood, and organ transplantation.
- Maternal manifestations of CMV infection can be asymptomatic or cause mononucleosis-like symptoms.
- Neonatal CMV infection can cause:
- Hearing loss (a leading cause of infectious hearing loss).
- Seizures.
- Petechial rash, often referred to as "blueberry muffin" rash.
CMV in Immunocompromised Patients
- CMV poses a serious and potentially fatal threat to immunocompromised patients, particularly AIDS and transplant patients.
- CMV can cause serious complications in immunocompromised patients, including colitis, retinitis, esophagitis, encephalitis, and pneumonitis (CREEP).
- CMV retinitis is a common complication that can lead to blindness.
Host Response to Primary HCMV Infection
- Primary HCMV infection leads to the rapid appearance of HCMV-specific TH1 CD4+ helper T cells.
- HCMV-specific TH1 CD4+ helper T cells release interferon-gamma (IFN-γ), a critical factor in controlling HCMV infection.
- T cells appear shortly after CMV is detected in the blood.
CMV: Infection Cycle
- CMV infection can be described in two phases:
- Productive Infection:
- Results in cell death.
- Produces new viruses.
- Immune control occurs through recognition of proteins expressed during this stage.
- Latent Infection:
- Viral genome persists in the absence of virus production.
- HCMV establishes latency in bone marrow hematopoietic progenitor cells.
- Limited immune control, due to the low expression of viral proteins.
- Reactivation of latency may be triggered by inflammation-associated signaling.
- Productive Infection:
CMV: Treatment and Prevention
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Treatment:
- Ganciclovir (valganciclovir) is used to treat solid organ transplant patients and those with severe CMV disease. It is also used prophylactically for transplant patients.
- Ganciclovir inhibits viral DNA synthesis.
- Immune globulin (CytoGam) is another treatment option used for transplant patients, those with severe CMV disease, and for primary infections diagnosed during pregnancy.
- Prophylactic treatment with ganciclovir is often used in high-risk transplant patients.
- Ganciclovir (valganciclovir) is used to treat solid organ transplant patients and those with severe CMV disease. It is also used prophylactically for transplant patients.
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Prevention:
- Educating parents and caregivers about CMV transmission is critical in breaking the chain of transmission, particularly among young children.
- Good personal hygiene and effective fomite disinfection are essential in preventing CMV spread.
HCMV Vaccine Challenges
- Adaptive immune responses are unable to completely clear HCMV infection (similar to other herpesviruses).
- Existing adaptive immunity offers only partial protection against new HCMV strains.
- Live attenuated HCMV vaccines are unlikely to be successful as they focus on preventing infection, rather than addressing the challenges of latency and reactivation.
- Therapeutic vaccines, aiming to boost T cell immunity in those already infected, are more likely to be effective.
- A deeper understanding of the differences between primary HCMV infection and reactivation is crucial for developing future vaccines.
Back to the Case
- Recipients of non-autologous grafts are highly immunocompromised due to treatments for graft rejection and graft-versus-host disease (GVHD), coupled with delayed T-cell reconstitution.
- HCMV pneumonia is a common and potentially life-threatening complication in transplant patients, arising from reactivation of latent infection or new infection.
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Description
This quiz covers crucial information about Cytomegalovirus (CMV) disease, including its effects on immunocompetent individuals and the implications of congenital infections. It also addresses the severe impact of CMV in immunocompromised patients such as those with AIDS and organ transplants. Test your knowledge on CMV transmission and its clinical significance.
