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Infection Disease – Cytomegalovirus Infection
CYTOMEGALOVIRUS INFECTION
ESSENTIALS DESCRIPTION
A collection of cytomegalovirus-induced infections of various organs and systems (CMV)
The study of epidemiology
The prevalence
• An estimated 27,000 new CMV infections among seronegative pregnant women occur annually in the United States; the rate of infection among individuals aged 10–49 is estimated to be 1.6 infections per 100 susceptible persons annually.
Prevalence: CMV is a prevalent human infection that impacts individuals all over the world.
• Higher CMV seroprevalence is linked to older age and lower socioeconomic level.
• Among those above the age of six, the estimated CMV seroprevalence rate in the United States is 60%. Among people over 80, the seroprevalence could be as high as 90%.
RISK ELEMENTS
• •
Immunosuppression increases the risk of developing severe CMV infection symptoms.
Having a CMV mismatch status is the main risk factor for illness in transplant recipients.
When a CMV-seropositive donor (CMV D+/R-) gives an allograft to a CMV-seronegative recipient, this is known as a solid organ transplant (SOT).
When a patient of an allogeneic bone marrow transplant receives a graft from a donor who is CMV-seronegative (CMV D–/R+), there is an increased risk.
Transplant recipients of the pancreas, small intestine, and lung are most vulnerable to infection. Recipients of heart and liver transplants are at intermediate risk. Those who have kidney transplants are at the lowest risk.
application of substances that deplete lymphocytes (e.g., OKT3, anti-thymocyte globulins, and anti-lymphocyte globulin).
acute rejection of allografts. illness caused by graft versus host.
HIV infection with fewer than 50/mm3 CD4 count.
• • • •
OVERALL PREVENTION
• Prophylactic antiviral treatment for recipients with CMV mismatch or CMV seropositive status. A growing issue among CMV D+/R-patients who were given antiviral prophylaxis is late-onset CMV illness.
• Some facilities utilize CMV immunoglobulin to prevent illness in high-risk persons (those who have received intestine and lung transplants and have CMV D+/R).
It is recommended that recipients of CMV-seronegative allogeneic hematopoietic stem cell transplants (AI) receive blood products from CMV-seronegative donors or leukocyte-depleted blood products.
• CMV-related illnesses in HIV infection have significantly decreased as a result of highly active antiretroviral therapy (HAART).
• No vaccination is currently available.
Pathophysiology
• When a CMV-seronegative recipient receives an allograft from a CMV-seropositive donor (CMV D+/R–), primary CMV infection occurs in SOT recipients.
• Reactivation happens when a seropositive recipient's latent virus reactivates during immunosuppressive episodes. Because of pre-existing anti-CMV immunity, the disease is less severe.
• The infection can be categorized as either symptomatic (CMV illness) or asymptomatic (subclinical CMV infection).
• The disease is further subdivided into tissue-invasive disease (disease with end-organ involvement) and CMV syndrome (disease without end-organ involvement).
• End-organ disease poses a special risk to the transplanted organ.
ETIOLOGY
• The herpesvirus category includes the DNA virus known as CMV.
• Like other viruses in the herpes group, CMV can cause latent infection following primary infection.
COMMON CONNECTED CIRCUMSTANCES
AIDS; solid organ transplantation; bone marrow transplantation; and patients with leukemia or lymphoma, which are severe cancer-related cellular immune suppression
History of Diagnosis
• In immunocompetent individuals, CMV may cause an infectious mononucleosis-like illness or be asymptomatic.
• The symptoms of CMV syndrome include fever, malaise, arthralgias, and myalgias.
• The most prevalent end-organ disease is colitis, which manifests as diarrhea and abdominal pain.
• The symptoms of CMV gastritis include nausea, vomiting, and odynophagia.
• The symptoms of pneumonia include fever, coughing, and dyspnea.
• Hepatitis and myocarditis are further symptoms.
A progressive loss of visual acuity brought on by chorioretinitis can lead to blindness. Following the start of HAART, reports of immune reconstitution syndrome have been made.
Lethargy, photophobia, and a severe headache are symptoms of meningoencephalitis.
Most often, HIV-infected patients experience back discomfort with spinal cord involvement (myelitis, polyradiculitis).
MEDICAL EXAMINATION
Splenomegaly, lymphadenopathy, and pharyngitis
• Rubelliform and maculopapular rashes when CMV mononucleosis is present.
• Signs of encephalitis in the pyramidal tract.
• In myeloradiculopathy, descending weakness in the lower limbs accompanied by a loss of deep tendon reflexes.
• Funduscopic observations in cases of retinitis: Peripheral lesions develop into central ones. regions with perivascular exudates that are yellow-white. There could be bleeding.
Tests for Diagnosis and Interpretation
Lab
First laboratory testing
• Anemia, hemolytic anemia, or thrombocytopenia brought on by myelosuppression.
• Atypical lymphocytes are present.
• A positive CMV IgG serology is a sign of latent virus but also indicates antiviral immunity. beneficial for assessing transplant candidates prior to transplantation as well as possible donors.
• Acute CMV infection or reactivation may result in the presence of IgM antibodies against CMV.
Note: Since immunosuppressed individuals are unable to mount an immunological response, serology is usually not helpful in these cases.
• Viral nucleic acid detection and antigenemia assays are currently the recommended diagnostic methods due to their quick turnaround time and great sensitivity.
• There are numerous real-time PCR platforms (2).
• Tagled monoclonal antibodies specific to the CMV pp65 matrix protein in peripheral blood polymorphonuclear leukocytes are used in CMV antigenemia testing. Because leukocytes are absent in neutropenic patients, their usefulness is restricted.
• CMV has been isolated from blood or other bodily fluids or tissues using viral culture. After one to six weeks, cytotoxic effects appear.
• The shell vial assay is a variation of viral culture. Results are sent out in a day or two.
Follow-up and Particular Points to Remember
• After two weeks of full-dose treatment, if there are still clinical symptoms and a growing or non-declining viral load, consider a drug-resistant virus.
• It is possible to test for genotypic resistance:
UL97 phosphotransferase mutations cause decreased amounts of the active triphosphorylated substance cause ganciclovir resistance. Less frequently, UL54 DNA polymerase mutations happen as second-step alterations following exposure to cidofovir, foscarnet, or ganciclovir. may cause the three antiviral medications to become resistant to one another.
Imaging: CMV encephalitis: periventricular inflammation or meningeal enhancement on the brain; CMV colitis: thickening of the bowel wall on CT imaging; and CMV pneumonitis: interstitial infiltrates on plain radiography. MRI
Diagnostic Techniques and Other
• Colonoscopy in CMV colitis reveals mucosal erythema, erosions, ulcerations, bleeding, and nodular or polypoid lesions; bronchoscopy with bronchoalveolar lavage/biopsy in CMV pneumonitis
Pathological Results
• Tissue invasion is not always associated with CMV viremia. One way to show CMV in tissue is by histology, immunohistochemistry, or in situ DNA hybridization. Large intranuclear inclusions encircled by a transparent halo are common cytopathic findings. There may also be smaller cytoplasmic inclusions.
DIFFERENTIAL DIAGNOSIS
HIV infection (including abrupt seroconversion), human herpesvirus 6 infection, infectious mononucleosis, toxoplasmosis, viral hepatitis, viral gastroenteritis, cryptosporidiosis, and Clostridium difficile infection
MEDICAL CARE
• CMV syndrome typically resolves on its own in the immunocompetent host and doesn't require medical intervention.
• Antiviral medications should be used vigorously to treat CMV infections in immunocompromised patients.
MEDICATION
First Phrase
• The preferred treatment is ganciclovir (AII). Dosage for induction: 5 mg/kg intravenously twice a day. For renal failure, the dosage is modified.
For mild-to-moderate illness, valganciclovir 900 mg p.o. twice daily may be administered as an induction treatment (3).
• Following a first intravenous ganciclovir induction treatment, valganciclovir is often utilized as a step-down oral medication.
• In AIDS patients with CMV retinitis, a sustained-release intraocular ganciclovir implant combined with a systemic drug works better than intravenous treatment alone
Line Two
• For ganciclovir-resistant CMV, provide 60 mg/kg intravenously every 8 hours (or 90 mg/kg intravenously every 12 hours) of foscarnet.
For ganciclovir-resistant CMV, a weekly dosage of 5 mg/kg of cidofovir is recommended. If creatinine clearance is less than 55 mL/min, it is contraindicated.
• In cases of low-level ganciclovir resistance, higher doses of ganciclovir (7.5–10 mg/kg i.v. every 12 hours) have been utilized.
ADDITIONAL MEDICATION
Overall Actions
decrease in immunosuppressive medication dosages
Other Treatments
CMV immunoglobulin for pneumonitis (BIII), a severe form of CMV illness
Continuing Care Follow-Up Suggestions
Monitoring of Patients
• Following the start of antiviral therapy, it is beneficial to assess disease activity every week using molecular tests or antigenemia.
• Generally speaking, patients should be treated for at least two to four weeks, ideally until two weeks after their CMV viremia has cleared up. Recurrent illness is linked to a lack of clearance
• It has also been suggested that maintenance therapy, which involves giving antiviral medications at preventative dosages, be used to finish treatment, which typically lasts up to three months.
PROGNOSIS
• A CMV infection can be fatal, particularly in people with impaired immune systems.
• One of the most serious CMV infections, particularly in bone marrow transplant recipients, is pneumonia.
The fatality rate for CMV encephalitis is very significant.
COMPLICATIONS
• Bowel perforation and peritonitis can result with CMV colitis.
• Congestive cardiac failure can result from CMV myocarditis.
• Patients with HIV may experience cauda equina syndrome.
• Effects of indirect CMV on transplant recipients:
Chronic allograft failure and acute allograft rejection
In receivers with the lungs, bronchiolitis obliterans; in recipients with the heart, accelerated vasculopathy - In liver recipients, disappearing bile duct syndrome
Tubulo-interstitial fibrosis and glomerulopathy (in kidney recipients)
• After the decline in rubella incidence brought on by vaccination, congenital CMV infection is the leading cause of congenital abnormalities in developed nations.
• Abortion, fetal jaundice, anemia, and damage to the central nervous system can result from a congenital CMV infection.
CYTOMEGALOVIRUS INFECTION
ESSENTIALS DESCRIPTION
A collection of cytomegalovirus-induced infections of various organs and systems (CMV)
The study of epidemiology
The prevalence
• An estimated 27,000 new CMV infections among seronegative pregnant women occur annually in the United States; the rate of infection among individuals aged 10–49 is estimated to be 1.6 infections per 100 susceptible persons annually.
Prevalence: CMV is a prevalent human infection that impacts individuals all over the world.
• Higher CMV seroprevalence is linked to older age and lower socioeconomic level.
• Among those above the age of six, the estimated CMV seroprevalence rate in the United States is 60%. Among people over 80, the seroprevalence could be as high as 90%.
RISK ELEMENTS
• •
Immunosuppression increases the risk of developing severe CMV infection symptoms.
Having a CMV mismatch status is the main risk factor for illness in transplant recipients.
When a CMV-seropositive donor (CMV D+/R-) gives an allograft to a CMV-seronegative recipient, this is known as a solid organ transplant (SOT).
When a patient of an allogeneic bone marrow transplant receives a graft from a donor who is CMV-seronegative (CMV D–/R+), there is an increased risk.
Transplant recipients of the pancreas, small intestine, and lung are most vulnerable to infection. Recipients of heart and liver transplants are at intermediate risk. Those who have kidney transplants are at the lowest risk.
application of substances that deplete lymphocytes (e.g., OKT3, anti-thymocyte globulins, and anti-lymphocyte globulin).
acute rejection of allografts. illness caused by graft versus host.
HIV infection with fewer than 50/mm3 CD4 count.
• • • •
OVERALL PREVENTION
• Prophylactic antiviral treatment for recipients with CMV mismatch or CMV seropositive status. A growing issue among CMV D+/R-patients who were given antiviral prophylaxis is late-onset CMV illness.
• Some facilities utilize CMV immunoglobulin to prevent illness in high-risk persons (those who have received intestine and lung transplants and have CMV D+/R).
It is recommended that recipients of CMV-seronegative allogeneic hematopoietic stem cell transplants (AI) receive blood products from CMV-seronegative donors or leukocyte-depleted blood products.
• CMV-related illnesses in HIV infection have significantly decreased as a result of highly active antiretroviral therapy (HAART).
• No vaccination is currently available.
Pathophysiology
• When a CMV-seronegative recipient receives an allograft from a CMV-seropositive donor (CMV D+/R–), primary CMV infection occurs in SOT recipients.
• Reactivation happens when a seropositive recipient's latent virus reactivates during immunosuppressive episodes. Because of pre-existing anti-CMV immunity, the disease is less severe.
• The infection can be categorized as either symptomatic (CMV illness) or asymptomatic (subclinical CMV infection).
• The disease is further subdivided into tissue-invasive disease (disease with end-organ involvement) and CMV syndrome (disease without end-organ involvement).
• End-organ disease poses a special risk to the transplanted organ.
ETIOLOGY
• The herpesvirus category includes the DNA virus known as CMV.
• Like other viruses in the herpes group, CMV can cause latent infection following primary infection.
COMMON CONNECTED CIRCUMSTANCES
AIDS; solid organ transplantation; bone marrow transplantation; and patients with leukemia or lymphoma, which are severe cancer-related cellular immune suppression
History of Diagnosis
• In immunocompetent individuals, CMV may cause an infectious mononucleosis-like illness or be asymptomatic.
• The symptoms of CMV syndrome include fever, malaise, arthralgias, and myalgias.
• The most prevalent end-organ disease is colitis, which manifests as diarrhea and abdominal pain.
• The symptoms of CMV gastritis include nausea, vomiting, and odynophagia.
• The symptoms of pneumonia include fever, coughing, and dyspnea.
• Hepatitis and myocarditis are further symptoms.
A progressive loss of visual acuity brought on by chorioretinitis can lead to blindness. Following the start of HAART, reports of immune reconstitution syndrome have been made.
Lethargy, photophobia, and a severe headache are symptoms of meningoencephalitis.
Most often, HIV-infected patients experience back discomfort with spinal cord involvement (myelitis, polyradiculitis).
MEDICAL EXAMINATION
Splenomegaly, lymphadenopathy, and pharyngitis
• Rubelliform and maculopapular rashes when CMV mononucleosis is present.
• Signs of encephalitis in the pyramidal tract.
• In myeloradiculopathy, descending weakness in the lower limbs accompanied by a loss of deep tendon reflexes.
• Funduscopic observations in cases of retinitis: Peripheral lesions develop into central ones. regions with perivascular exudates that are yellow-white. There could be bleeding.
Tests for Diagnosis and Interpretation
Lab
First laboratory testing
• Anemia, hemolytic anemia, or thrombocytopenia brought on by myelosuppression.
• Atypical lymphocytes are present.
• A positive CMV IgG serology is a sign of latent virus but also indicates antiviral immunity. beneficial for assessing transplant candidates prior to transplantation as well as possible donors.
• Acute CMV infection or reactivation may result in the presence of IgM antibodies against CMV.
Note: Since immunosuppressed individuals are unable to mount an immunological response, serology is usually not helpful in these cases.
• Viral nucleic acid detection and antigenemia assays are currently the recommended diagnostic methods due to their quick turnaround time and great sensitivity.
• There are numerous real-time PCR platforms (2).
• Tagled monoclonal antibodies specific to the CMV pp65 matrix protein in peripheral blood polymorphonuclear leukocytes are used in CMV antigenemia testing. Because leukocytes are absent in neutropenic patients, their usefulness is restricted.
• CMV has been isolated from blood or other bodily fluids or tissues using viral culture. After one to six weeks, cytotoxic effects appear.
• The shell vial assay is a variation of viral culture. Results are sent out in a day or two.
Follow-up and Particular Points to Remember
• After two weeks of full-dose treatment, if there are still clinical symptoms and a growing or non-declining viral load, consider a drug-resistant virus.
• It is possible to test for genotypic resistance:
UL97 phosphotransferase mutations cause decreased amounts of the active triphosphorylated substance cause ganciclovir resistance. Less frequently, UL54 DNA polymerase mutations happen as second-step alterations following exposure to cidofovir, foscarnet, or ganciclovir. may cause the three antiviral medications to become resistant to one another.
Imaging: CMV encephalitis: periventricular inflammation or meningeal enhancement on the brain; CMV colitis: thickening of the bowel wall on CT imaging; and CMV pneumonitis: interstitial infiltrates on plain radiography. MRI
Diagnostic Techniques and Other
• Colonoscopy in CMV colitis reveals mucosal erythema, erosions, ulcerations, bleeding, and nodular or polypoid lesions; bronchoscopy with bronchoalveolar lavage/biopsy in CMV pneumonitis
Pathological Results
• Tissue invasion is not always associated with CMV viremia. One way to show CMV in tissue is by histology, immunohistochemistry, or in situ DNA hybridization. Large intranuclear inclusions encircled by a transparent halo are common cytopathic findings. There may also be smaller cytoplasmic inclusions.
DIFFERENTIAL DIAGNOSIS
HIV infection (including abrupt seroconversion), human herpesvirus 6 infection, infectious mononucleosis, toxoplasmosis, viral hepatitis, viral gastroenteritis, cryptosporidiosis, and Clostridium difficile infection
MEDICAL CARE
• CMV syndrome typically resolves on its own in the immunocompetent host and doesn't require medical intervention.
• Antiviral medications should be used vigorously to treat CMV infections in immunocompromised patients.
MEDICATION
First Phrase
• The preferred treatment is ganciclovir (AII). Dosage for induction: 5 mg/kg intravenously twice a day. For renal failure, the dosage is modified.
For mild-to-moderate illness, valganciclovir 900 mg p.o. twice daily may be administered as an induction treatment (3).
• Following a first intravenous ganciclovir induction treatment, valganciclovir is often utilized as a step-down oral medication.
• In AIDS patients with CMV retinitis, a sustained-release intraocular ganciclovir implant combined with a systemic drug works better than intravenous treatment alone
Line Two
• For ganciclovir-resistant CMV, provide 60 mg/kg intravenously every 8 hours (or 90 mg/kg intravenously every 12 hours) of foscarnet.
For ganciclovir-resistant CMV, a weekly dosage of 5 mg/kg of cidofovir is recommended. If creatinine clearance is less than 55 mL/min, it is contraindicated.
• In cases of low-level ganciclovir resistance, higher doses of ganciclovir (7.5–10 mg/kg i.v. every 12 hours) have been utilized.
ADDITIONAL MEDICATION
Overall Actions
decrease in immunosuppressive medication dosages
Other Treatments
CMV immunoglobulin for pneumonitis (BIII), a severe form of CMV illness
Continuing Care Follow-Up Suggestions
Monitoring of Patients
• Following the start of antiviral therapy, it is beneficial to assess disease activity every week using molecular tests or antigenemia.
• Generally speaking, patients should be treated for at least two to four weeks, ideally until two weeks after their CMV viremia has cleared up. Recurrent illness is linked to a lack of clearance
• It has also been suggested that maintenance therapy, which involves giving antiviral medications at preventative dosages, be used to finish treatment, which typically lasts up to three months.
PROGNOSIS
• A CMV infection can be fatal, particularly in people with impaired immune systems.
• One of the most serious CMV infections, particularly in bone marrow transplant recipients, is pneumonia.
The fatality rate for CMV encephalitis is very significant.
COMPLICATIONS
• Bowel perforation and peritonitis can result with CMV colitis.
• Congestive cardiac failure can result from CMV myocarditis.
• Patients with HIV may experience cauda equina syndrome.
• Effects of indirect CMV on transplant recipients:
Chronic allograft failure and acute allograft rejection
In receivers with the lungs, bronchiolitis obliterans; in recipients with the heart, accelerated vasculopathy - In liver recipients, disappearing bile duct syndrome
Tubulo-interstitial fibrosis and glomerulopathy (in kidney recipients)
• After the decline in rubella incidence brought on by vaccination, congenital CMV infection is the leading cause of congenital abnormalities in developed nations.
• Abortion, fetal jaundice, anemia, and damage to the central nervous system can result from a congenital CMV infection.
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