Materiały źródłowe

• #1 Diagnosis of Cytomegalovirus Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3730495/

  Cytomegalovirus (CMV) is recognized as the most common congenital viral infection in humans and an important cause of morbidity and mortality in immunocompromised hosts. […] This recognition of the clinical importance of invasive CMV disease in the setting of immunodeficiency and in children with congenital CMV infection has led to the development of new diagnostic procedures for the rapid identification of immunocompromised individuals with CMV disease, as well as fetuses and infants with congenital infection. Diagnosis of acute maternal CMV infection by the presence of IgM and low IgG avidity requires confirmation of fetal infection which is typically performed by CMV PCR of the amniotic fluid. […] Viral culture of the urine and saliva obtained within the first two weeks of life continue to be the gold standard for diagnosis of congenitally infected infants. […] However, saliva PCR assays are currently being assessed as a useful screening method for congenital CMV infection. In the immunocompromised host, newer rapid diagnostic assays such as pp65 antigenemia and real-time CMV PCR of blood or plasma have allowed for preemptive treatment reducing morbidity and mortality. […] However, lack of standardized real-time PCR protocols hinders the comparison of the data across different centers and the development of uniform guidelines for the management of invasive CMV infections in immunocompromised individuals.

• #1 Cytomegalovirus (CMV) Infection – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/herpesviruses/cytomegalovirus-cmv-infection

  Cytomegalovirus (CMV, human herpesvirus type 5) can cause infections that have a wide range of severity. […] Laboratory diagnosis, helpful for severe disease, may involve culture, serologic testing, biopsy, or antigen or nucleic acid detection. […] Diagnosis of CMV infection in infants can be made by urine culture. […] CMV mononucleosis can be differentiated from infectious (EBV) mononucleosis by the usual lack of pharyngitis, a negative heterophile antibody test, and positive CMV serologic testing. […] Laboratory confirmation of primary CMV infection is necessary only to differentiate it from other, particularly treatable, conditions or serious disease, such as primary HIV. […] Quantitative detection of CMV antigen or DNA in the peripheral blood can also be very helpful because an elevated or rising CMV viral load is often highly suggestive of invasive disease. […] Prophylaxis or preemptive treatment (actively monitoring patients by viral load and giving antivirals to those with evidence of infection) is effective for preventing CMV disease in solid organ or hematopoietic cell transplant recipients infected with CMV and at risk of CMV disease.

• #1 Laboratory Testing for CMV and Congenital CMV | Cytomegalovirus (CMV) and Congenital CMV Infection | CDC

  https://www.cdc.gov/cytomegalovirus/php/laboratories/index.html

  The enzyme-linked immunosorbent assay is the most common serologic test for measuring antibody to CMV. […] Congenital CMV infection cannot be diagnosed with antibody testing (IgG and IgM). […] The standard laboratory test for diagnosing congenital CMV infection is a PCR on saliva, with a confirmatory test on urine. […] Polymerase chain reaction (PCR) on saliva is the standard laboratory test for diagnosing congenital CMV infection. Urine is usually collected and tested for confirmation. […] Currently, testing of newborns for CMV is not routinely performed, though some states perform targeted CMV testing of newborns who fail the hearing screening. […] A positive test for CMV IgG indicates that a person was infected with CMV at some time during their life but does not indicate when a person was infected.

• #1 Laboratory Testing for CMV and Congenital CMV | Cytomegalovirus (CMV) and Congenital CMV Infection | CDC

  https://www.cdc.gov/cytomegalovirus/php/laboratories/index.html

  Measurement of CMV IgG in paired samples taken one to three months apart can be used to diagnose primary infection. […] The presence of CMV IgM cannot be used by itself to diagnose primary CMV infection because IgM can also be present during secondary CMV infection. […] IgG avidity assays measure the binding strength between IgG antibodies and virus that can help distinguish a primary CMV infection from a past infection.

• #1 Cytomegalovirus (CMV) Antibodies, IgG, Serum » Incyte Diagnostics

  https://www.incytediagnostics.com/laboratory-services/test-directory/TestDetails/cytomegalovirus-cmv-antibodies-igg-serum

  Useful for determining whether a patient (especially transplant recipients, organ and blood donors) has had a recent infection or previous exposure to cytomegalovirus […] Sera drawn very early during the acute stage of infection may have undetectable levels of cytomegalovirus (CMV) IgG. The CMV IgG assay should not be used alone to diagnose CMV infection. Results should be considered in conjunction with clinical presentation, patient history, and other laboratory findings. In cases of suspected disease, submit a second specimen for testing in 10 to 14 days […] The performance characteristics of this assay have not been evaluated in immunosuppressed or organ transplant recipients and have not been established for cord blood or for testing of neonates […] Immune complexes or other immunoglobulin aggregates present in patient samples may cause increased nonspecific binding and produce false-positive results […] Potential cross-reactivity for CMV with human chorionic gonadotropin, HIV IgG, multiple myeloma IgG, rheumatoid factor IgM, and Toxoplasma gondii IgG have not be ruled out.

• #1 Diagnosis of Cytomegalovirus Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3730495/

  The traditional method for detecting CMV is through conventional cell culture. […] Shell vial assay is a modified viral culture by a centrifugation-amplification technique designed to decrease the length of time needed for rapid virus detection. […] The antigenemia assay has been commonly used for more than a decade for CMV virus quantification in blood specimens. […] The disadvantages of the antigenemia assay are that it is labor intensive with low throughput and not amenable to automation. […] Polymerase chain reaction (PCR) is a widely available rapid and sensitive method of CMV detection based on amplification of nucleic acids. […] PCR for CMV DNA can be either qualitative or quantitative, in which the amount of viral DNA in the respective sample is measured. […] Reverse transcriptase (RT-PCR) can be used to detect viral mRNA transcripts in peripheral blood leukocytes independent of the presence of DNA.

• #1 Cytomegalovirus – CMV | Choose the Right Test

  https://arupconsult.com/content/cytomegalovirus

  CMV IgM testing cannot be used alone to diagnose primary CMV infection. However, it may be used alongside IgG avidity testing to confirm a current infection. […] Quantitative NAAT (eg, qPCR) for viral DNA in plasma or whole blood is the primary test for detecting CMV infection in immunocompromised patients because this test quantifies viral load, provides rapid and early detection, and offers higher sensitivity than culture. […] Testing for CMV infection in pregnant individuals generally occurs after concerning ultrasound findings. […] When primary CMV infection is suspected during pregnancy, serologic assays are the main tests used for evaluation. […] In newborns, NAAT using saliva is initially performed to identify CMV infection. […] Following transplantation, quantitative NAAT performed on plasma or whole blood is recommended to screen for CMV infection in at-risk individuals, guide preemptive treatment, diagnose a current infection, and monitor response to antiviral therapies.

• #1 Decoding human cytomegalovirus for the development of innovative diagnostics to detect congenital infection | Pediatric Research

  https://www.nature.com/articles/s41390-023-02957-9

  An overview of current and emerging diagnostics is provided in Table 2. […] Viral cultures, employing fibroblast monolayers, are also used in clinical laboratories. […] FDA-approved commercially available NAAT kits are listed in Table 3. […] Saliva is collected by oral (not throat) swab and is usually more convenient to obtain than urine in the first 24 hours of life, as urine production is limited. […] Digital PCR (dPCR) maybe a more precise, reproducible, and quantifiable assay than real-time quantitative PCR (qPCR), especially in samples with low viral load. […] While routine monitoring of viral burden is not currently advocated for neonates with moderate to severe symptomatic cCMV disease treated with ganciclovir (GCV) or valganciclovir (VGCV) for less than six months, recent investigations have reported antiviral resistance with prolonged courses (6 months).

• #1 Cytomegalovirus (CMV) Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/215702-workup

  Antigenemia is defined as the detection of the CMV pp65 antigen in leukocytes. […] The pp65 assay is used to detect messenger matrix proteins on the CMV virus, with either immunofluorescence assay or messenger RNA amplification. These proteins typically are expressed only during viral replication. Antigen tests often are the basis for institution of antiviral therapy in transplant recipients and may allow for the detection of subclinical disease in high-risk patients. The assay is sensitive and specific and yields results quickly. […] In immunocompromised patients, low or moderate CMV antigenemia may indicate reactivation or infection. […] It has been reported that the pp65 antigen assay and quantitative CMV PCR yield similar effectiveness in diagnosing and monitoring patients with active CMV infection.

• #1 Cytomegalovirus (CMV) Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/215702-workup

  Qualitative PCR is used to detect CMV in blood and tissue samples. […] Qualitative PCR is extremely sensitive, but, because CMV DNA can be detected in patients with or without active disease, the clinical utility of qualitative PCR is limited. […] In transplant recipients, a negative CMV PCR result goes against reactivation, but not infection. […] Quantitative PCR has been used to detect plasma CMV. […] A study of more than 3400 blood specimens from organ transplant recipients tested with CMV PCR and pp65 antigenemia found that quantitative real-time PCR for CMV DNA could be used in lieu of antigenemia for monitoring CMV infection and determining when to initiate preemptive treatment. […] The hallmark of CMV infection is the finding of intranuclear inclusions consistent with herpesvirus infection. CMV infection may be confirmed using in situ hybridization or direct or indirect staining of intranuclear inclusions using CMV-specific antibodies linked to an indicator system.

• #1 Cytomegalovirus | AAFP

  https://www.aafp.org/pubs/afp/issues/2003/0201/p519.html

  CMV polymerase chain reaction (PCR) or culture is not useful in the diagnosis of primary CMV infection, because a positive test may just reflect viral shedding via a transient reactivation from the latent state. […] Histologically, the detection of the distinct owl’s eye inclusion bodies on tissue sample can be a highly specific method for determining organ involvement of CMV.

• #1 Congenital and Perinatal Cytomegalovirus Infection (CMV) – Pediatrics – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/pediatrics/infections-in-neonates/congenital-and-perinatal-cytomegalovirus-infection-cmv

  Cytomegalovirus infection may be acquired prenatally or perinatally and is the most common congenital viral infection. […] Diagnosis of neonatal infection is by nucleic acid amplification testing. […] In neonates, viral detection using culture or PCR of urine, saliva, blood, or a tissue sample is the primary diagnostic tool; maternal diagnosis can also be made by serologic testing or PCR (see Diagnosis of CMV). […] Congenital CMV infection is diagnosed if the virus (or viral nucleic acid) is identified in urine, saliva, or other body fluids obtained within the first 3 weeks of life; urine and saliva have the highest sensitivity. […] Fetal CMV infection can be confirmed by PCR testing for CMV in the amniotic fluid. […] Distinguish symptomatic congenital CMV infection from other congenital infections (eg, toxoplasmosis, rubella, lymphocytic choriomeningitis, syphilis) using polymerase chain reaction (PCR) testing or viral culture.

• #1 Cytomegalovirus (CMV) Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/215702-workup

  In congenital CMV disease, laboratory abnormalities may include abnormal transaminases, bilirubin and platelet levels. To diagnose congenital CMV infection, testing should be performed within the first 3 weeks of life, because testing past this period does not differentiate intrauterine from perinatal acquisition of CMV infection. Saliva CMV PCR is the preferred diagnostic test for newborn congenital CMV screening, because high viral loads are shed in both urine and saliva in infants with congenital CMV. Due to some false-positive results in breastfeeding patients, obtaining a sample of saliva at least 1 hour after could avoid potential contamination with CMV from human milk. Other recommended tests include polymerase chain reaction (PCR) in blood and urine as well. […] The prognostic value of CMV viral load in neonatal samples, especially with asymptomatic infection, is unclear. The role of virus burden in the peripheral blood, urine, and saliva in disease and outcome needs further study.

• #1 Diagnosis of Cytomegalovirus Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3730495/

  Detection of CMV in the amniotic fluid has been the standard for diagnosis of infection of the fetus. […] With the advent of PCR, detection of CMV DNA in amniotic fluid has shown to improve prenatal diagnosis of congenital CMV infection. […] The highest sensitivity of this assay (90-100%) has been shown when amniotic fluid samples are obtained after the 21st week of gestation and at least 6 weeks after the first positive maternal serologic assay. […] The diagnosis of congenital CMV infection is typically made by the demonstration of the virus or viral antigens in newborn samples, urine or saliva. […] Serological methods are unreliable for the diagnosis of congenital infection. […] Detection of CMV in the saliva and urine of infants is easily accomplished because newborns with congenital CMV infection shed large amounts of virus. […] The CMV antigenemia assay, which detects the pp65 protein in polymorphonuclear leucocytes, is used widely to diagnose CMV infections and monitor treatment in immunocompromised patients. […] However, the utility of this assay in the diagnosis of congenital CMV infection has not been evaluated.

• #1 Cytomegalovirus (CMV) infection – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/cmv/diagnosis-treatment/drc-20355364

  Laboratory tests including tests of blood and other body fluids or tests of tissue samples can detect cytomegalovirus (CMV). […] If your doctor detects a new CMV infection while you’re pregnant, a prenatal test (amniocentesis) can determine whether the fetus has been infected. […] Testing for CMV can also be important if you have a weakened immune system. […] If your baby has CMV, your doctor likely will recommend additional tests to check the health of the baby’s organs, such as the liver and kidneys. […] Antiviral medications are the most common type of treatment. They can slow reproduction of the virus, but can’t eliminate it.

• #1 Update on congenital cytomegalovirus infection: Prenatal prevention, newborn diagnosis, and management | Canadian Paediatric Society

  https://cps.ca/documents/position/update-on-congenital-cytomegalovirus-infection-prenatal-prevention-newborn-diagnosis-and-management

  Infants born to mothers with suspected or proven CMV during pregnancy (based on maternal symptoms, serology, fetal ultrasonographic features, or placental histopathology), or infants with risk factors or clinical features compatible with cCMV, should undergo CMV testing and clinical and laboratory evaluation to determine disease classification. […] A negative urine or saliva CMV test should trigger investigations for other congenital infectious or genetic causes. […] Newborns who fail their newborn hearing screen (NBHS) are also being tested for CMV. […] Although universal screening would (ideally) optimize detection of cCMV, consensus is needed concerning the optimal specimen to use for early newborn screening. […] When testing has confirmed cCMV, symptomatic infants require ophthalmological and hearing evaluation as well as head imaging.

• #1 Update on congenital cytomegalovirus infection: Prenatal prevention, newborn diagnosis, and management | Canadian Paediatric Society

  https://cps.ca/documents/position/update-on-congenital-cytomegalovirus-infection-prenatal-prevention-newborn-diagnosis-and-management

  For asymptomatic or minimally symptomatic infants, a head ultrasound (HUS) is usually sufficient. […] All moderate to severe CMV cases should be referred promptly for infectious disease consultation. […] Antiviral treatment should commence in first month of life and be administered for 6 months. […] There is no evidence to support antiviral therapy for asymptomatic CMV disease without SNHL at the present time. […] Mild CMV is characterized by transient or minor abnormalities in one or two organ systems, with no CNS involvement. […] All infants with symptomatic cCMV and asymptomatic infants with isolated hearing loss should be referred to an infectious disease specialist. […] Affected infants require multidisciplinary follow-up.

• #1 Cytomegalovirus (CMV) in Pregnancy | ACOG

  https://www.acog.org/clinical-information/physician-faqs/cytomegalovirus-in-pregnancy

  Cytomegalovirus (CMV) is a ubiquitous double-stranded DNA herpesvirus that is transmitted by sexual contact or direct contact with infected blood, urine, or saliva. After an incubation period of 28-60 days (mean, 40 days), CMV infection induces immunoglobulin M (IgM) antibody production followed by an IgG antibody response. Viremia can be detected for 2-3 weeks after primary infection (infection in a previously seronegative individual). After the primary infection, CMV remains latent in host cells and recurrent, or secondary, infection can occur. […] Cytomegalovirus infection can occur during pregnancy. The incidence of primary CMV infection among previously seronegative pregnant people in the United States ranges from 0.3% to 4%. For those who are seropositive before a pregnancy, developing a secondary CMV infection is a possibility, although there are no clinically available diagnostic assays to detect secondary infection. Secondary infection can be due to either a reactivation or a reinfection with another viral strain.

• #1 Cytomegalovirus – CMV | Choose the Right Test

  https://arupconsult.com/content/cytomegalovirus

  Pregnant individuals with possible active CMV infection, which may affect the fetus. […] Neonates with congenital syndromes suggestive of CMV. […] Prospective transplant donors and prospective or recent transplant recipients. […] Immunocompetent patients who present with mononucleosis-like illness and have tested negative for Epstein-Barr virus (EBV). […] Screening for primary cytomegalovirus (CMV) infection is not currently recommended for pregnant individuals in the United States. […] Cytomegalovirus (CMV) can be detected by nucleic acid amplification testing (NAAT), serology, viral culture, and histology. […] Quantitative nucleic acid amplification testing (NAAT) is preferred to monitor viral loads and antiviral treatment response in transplant recipients. […] In patients 12 months or older, a positive cytomegalovirus (CMV) immunoglobulin G (IgG) result suggests a past infection, whereas paired IgG results demonstrating seroconversion indicate a recent infection.

• #1 Cytomegalovirus (CMV) in Pregnancy | ACOG

  https://www.acog.org/clinical-information/physician-faqs/cytomegalovirus-in-pregnancy

  Routine serologic screening of pregnant individuals for CMV is not recommended. The vast majority (approximately 90%) of positive IgM results are false positive and likely due to cross-reactivity with other non-CMV antibodies. The limitations of maternal IgM antibody screening in differentiating primary from recurrent infection also make the results difficult to use in counseling patients about fetal risk. […] Most adult CMV infections are asymptomatic, which makes recognition of primary infection difficult. Cytomegalovirus infection in adults usually is established by serologic testing. Serum samples collected 3-4 weeks apart, tested in parallel for anti-CMV IgG, are pathognomonic for the diagnosis of primary infection. Seroconversion from negative to positive or a significant increase (greater than fourfold [eg, from 1:4 to 1:16]) in anti-CMV IgG titers is evidence of infection.

• #1 Society for Maternal-Fetal Medicine Consult Series #39: Diagnosis and antenatal management of congenital cytomegalovirus infection – SMFM Publications and Clinical Guidelines

  https://publications.smfm.org/publications/585-society-for-maternal-fetal-medicine-consult-series-39/

  Congenital cytomegalovirus (CMV) is the most common viral infection, affecting nearly 40,000 infants each year in the United States. The purpose of this document is to review diagnosis of primary maternal CMV infection, diagnosis of fetal CMV infection, and whether antenatal therapy is warranted. We recommend the following: (1) that women with a diagnosis of primary CMV infection in pregnancy be advised that the risk of congenital infection is 30-50%, on average, and that the severity of infection varies widely (Best Practice); (2) for women suspected of having primary CMV infection in pregnancy, we recommend that diagnosis should be either by IgG seroconversion or with positive CMV IgM, positive IgG, and low IgG avidity (grade 1B); (3) amniocentesis is the best option as a prenatal diagnostic tool to detect fetal congenital CMV infection, performed 21 weeks of gestation and 6 weeks from maternal infection (grade 1C); (4) we do not recommend routine screening of all pregnant women for evidence of primary CMV infection at this time (grade 1B); and (5) we do not recommend antenatal treatment with ganciclovir or valacyclovir; and we recommend that any antenatal therapy, either with antivirals or CMV hyperimmune globulin, should only be offered as part of a research protocol (Best Practice).

• #1 Cytomegalovirus (CMV) in Pregnancy | ACOG

  https://www.acog.org/clinical-information/physician-faqs/cytomegalovirus-in-pregnancy

  After detection of maternal infection or suspected fetal infection based on ultrasound findings, CMV can be detected in the amniotic fluid of infected fetuses by either culture or PCR. […] Currently, no therapies are approved by the U.S. Food and Drug Administration (FDA) for the treatment of maternal or fetal CMV infection. Antiviral medications such as ganciclovir, valganciclovir, and foscarnet are approved by the FDA for the treatment of CMV infection only in patients with acquired immunodeficiency syndrome or organ transplants. […] In cases of known maternal CMV infection, referral to a maternal-fetal medicine or infectious disease specialist with expertise in pregnancy management may be warranted. Typically, serial ultrasonographic surveillance that includes assessment of fetal anatomy (eg, the cerebral ventricles) and growth is performed.

• #1 Cytomegalovirus (CMV): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/215702-overview

  CMV has been detected via culture, serologies, antigen assays, polymerase chain reaction (PCR), and cytopathology. In the transplant population, antigen assays or PCR is used (sometimes in conjunction with cytopathology) for diagnosis and treatment determinations. […] The diagnosis of CMV pneumonia can be suggested by chest radiography findings, but these findings cannot be used to differentiate between other common causes of pneumonia in immunocompromised hosts. A chest radiograph finding consistent with pneumonia and a bronchoalveolar lavage (BAL) result that is CMV positive is a common method for diagnosis. […] Infection is defined as isolation of CMV, its viral proteins, or its nucleic acid from any tissue sample or body fluid. […] Clinically significant CMV disease (reactivation of previously latent infection or newly acquired infection) frequently develops in patients immunocompromised by HIV infection, solid-organ transplantation, or bone marrow transplantation, as well as in those receiving high-dose steroids, tumor necrosis antagonists, or other immunosuppressing medications for conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Crohn disease, or psoriasis, among others.

• #1 Cytomegalovirus Disease: Adult and Adolescent OIs | NIH

  https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/cytomegalovirus

  Cytomegalovirus (CMV) is a double-stranded DNA virus in the herpesvirus family that can cause disseminated or localized end-organ disease in people with HIV with advanced immunosuppression. Most clinical disease occurs in individuals previously infected with CMV experiencing reactivation of latent infection. Infection with a novel strain also may occur. […] End-organ disease caused by CMV occurs in patients with HIV and advanced immunosuppression, typically those with CD4+ T lymphocyte cell (CD4) counts 50 cells/mm3 who are not receiving, adherent to, or responding to antiretroviral therapy (ART). Among those treated with ART who have achieved virologic control, a new diagnosis of CMV end-organ disease is exceedingly rare. […] The diagnosis of CMV end-organ disease is typically made on the basis of the clinical presentation and, when possible, evidence of the virus in tissue. CMV retinitis usually is diagnosed based on recognition of characteristic retinal changes observed through a dilated pupil during an ophthalmoscopic examination performed by an experienced ophthalmologist. Diagnosis in that setting has a 95% positive predictive value.

• #1 Cytomegalovirus Disease: Adult and Adolescent OIs | NIH

  https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/cytomegalovirus

  Blood tests to detect CMV by antigen detection, culture, or PCR are not recommended for diagnosis of CMV end-organ disease because of their poor positive predictive value in people with advanced AIDS. […] The presence of serum antibodies to CMV, in and of itself, does not establish the presence of CMV disease, because a large proportion of the general population has been exposed to CMV and is seropositive. However, a negative immunoglobulin G (IgG) antibody level indicates that CMV is unlikely to be the cause of the disease process. […] CMV end-organ disease is best prevented using ART to maintain the CD4 count 100 cells/mm3. […] The primary method for preventing severe CMV disease is recognizing the early manifestations of the disease and instituting proper therapy. […] The therapeutic approach to CMV retinitis should be individualized based on tolerance of systemic medications, prior exposure to anti-CMV drugs, and possibly the location of lesions.

• #1 Cytomegalovirus (CMV) Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/215702-workup

  The diagnosis of CMV pneumonia can be suggested by chest radiography findings, but these findings cannot be used to differentiate between other common causes of pneumonia in immunocompromised hosts. A chest radiograph finding consistent with pneumonia and a BAL result that is CMV positive is a common method for diagnosis. […] If resistant CMV infection is suspected (refractory to IV ganciclovir or valganciclovir therapy), an alternative therapy should be used based on genetic resistance. UL54 mutation is associated with ganciclovir resistance and a cross-resistance with cidofovir. UL97 mutation is also associated with ganciclovir resistance. […] The diagnosis of CMV infection can be confirmed using various laboratory tests, including PCR and antigen assays.

• #1 Cytomegalovirus – CMV | Choose the Right Test

  https://arupconsult.com/content/cytomegalovirus

  Most healthy individuals who acquire CMV after birth experience few symptoms and no long-term health consequences. However, testing for CMV may be indicated in immunocompetent individuals who present with mononucleosis-like symptoms once EBV has been excluded. […] When antiviral resistance is suspected, consensus guidelines recommend testing for causative variants in the UL97 and UL54 genes, at a minimum.

• #1 Cytomegalovirus infection – Knowledge @ AMBOSS

  https://www.amboss.com/us/knowledge/cytomegalovirus-infection/

  Diagnosis is based on serology findings or the direct detection of the virus in blood or tissue. […] In patients with clinical features of CMV, obtain CMV-specific studies based on immune status. […] Obtain directed studies (e.g., fundoscopy, chest x-ray, endoscopy) based on the clinical manifestation. […] If there are concerns for organ involvement, obtain a tissue biopsy for a definitive diagnosis. […] Serological tests: Obtain in immunocompetent patients. […] Direct viral detection: Obtain in patients with immunocompromise. […] Tissue biopsy […] Histopathology: large atypical cells with intranuclear inclusion bodies that have an owl-eye appearance. […] Immunohistochemistry: detection of CMV antigens. […] Serum viral detection (e.g., CMV PCR) is often negative and therefore not useful in patients with suspected CMV retinitis, colitis, or pneumonitis. […] Recommended before HSCT or solid organ transplant. […] Not routinely recommended for pregnant individuals or those planning pregnancy.

• #1 Cytomegalovirus Disease: Adult and Adolescent OIs | NIH

  https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/cytomegalovirus

  CMV colitis usually is diagnosed based on demonstration of mucosal ulcerations on endoscopic examination, combined with histopathologic demonstration of characteristic intranuclear and intracytoplasmic inclusions on hematoxylin and eosin stains. Similarly, CMV esophagitis is diagnosed by presence of ulcers of the distal esophagus together with biopsy evidence of intranuclear inclusion bodies in the endothelial cells with an inflammatory reaction at the edge of the ulcer. […] The diagnosis of CMV pneumonitis requires consistent clinical and radiological findings (i.e., diffuse pulmonary interstitial infiltrates, fever, and cough or dyspnea), identification of multiple CMV inclusion bodies in lung tissue or cytology, and the absence of any other pathogens that are more commonly associated with pneumonitis.

• #1 Detection of cytomegalovirus (CMV) by digital PCR in stool samples for the non-invasive diagnosis of CMV gastroenteritis | Virology Journal | Full Text

  https://virologyj.biomedcentral.com/articles/10.1186/s12985-022-01913-z

  Noninvasive methods, such as CMV DNA segment detection by qPCR from immunocompromised patients stool samples, are considered a potential substitution for gastrointestinal biopsy. […] Several studies have revealed that PCR-based stool tests for the detection of CMV DNA segment were valuable in the diagnosis of CMV gastroenteritis or at least in ruling it out. […] The dPCR approach was also reported to perform better on inhibition-prone stool samples than a qPCR assay in CMV detection. […] We show that detecting CMV in stool cfDNA by dPCR was sensitive and relevant in the diagnosis of intestinal CMV infection in immunocompromised patients. […] The total positive rate was 28%, indicating that more than one-quarter of the gastrointestinal symptoms within these immunosuppressed patients may be caused by CMV infection or reactivation. […] In conclusion, the detection of CMV by dPCR in cfDNA of stool supernatant is a powerful method to identify CMV gastroenteritis, which exhibits higher efficiency and sensitivity and helps in clinical treatment decision making.

• #1 Cytomegalovirus (CMV) Infection: Causes & Symptoms

  https://my.clevelandclinic.org/health/diseases/21166-cytomegalovirus

  A provider can treat CMV with the antiviral medications ganciclovir (GCV) or valganciclovir (VGC). These drugs are given directly into your vein (IV infusion) or swallowed in a pill. Providers usually only treat CMV in people who have a compromised immune system or babies who are born with symptoms of CMV. […] If you’re pregnant or have a compromised immune system, you can reduce your risk of CMV by avoiding contact with other people’s body fluids. […] Once infected, CMV can stay in your body, inactive, for the rest of your life. If you have a weakened immune system, it can reactivate and cause serious symptoms or organ damage. […] Early identification and treatment are the best ways to manage the effects of CMV and to prevent serious complications in those most at risk.

• #1 Congenital Cytomegalovirus Infection: Update on Diagnosis and Treatment

  https://www.mdpi.com/2076-2607/8/10/1516

  Congenital cytomegalovirus (cCMV) infection is the most common congenital viral infection and is the leading non-genetic cause of sensorineural hearing loss (SNLH) and an important cause of neurodevelopmental disabilities. […] Despite its prevalence and morbidity among the neonatal population, there is not yet a standardized diagnostic test and therapeutic approach for cCMV infection. […] Currently, we recommend using a PCR assay in blood, urine, and saliva in neonates with suspected cCMV infection. […] At present, there is no evidence of the benefit of antiviral therapy in asymptomatic infants. […] In the case of symptomatic cCMV, we actually recommend treatment with oral valganciclovir for a duration of 12 months. […] The effectiveness and tolerability of this therapy option have proven effective for hearing and neurodevelopmental long-term outcomes.

• #1 Cytomegalovirus (CMV) – congenital and postnatal infection | NHSGGC

  https://clinicalguidelines.scot.nhs.uk/ggc-paediatric-guidelines/ggc-paediatric-guidelines/neonatology/cytomegalovirus-cmv-congenital-and-postnatal-infection/

  There is currently no universal screening program for CMV. […] The diagnosis of congenital infection is made by PCR testing of body fluids in the first 3 weeks of life but ideally within the first 2 weeks. […] Both urine and salivary swabs should be tested by PCR where CMV is suspected. […] If CMV infection is diagnosed after 3 weeks of age it may be unclear whether the infection is congenital. […] Treatment may still be considered in infants with evidence of CNS involvement or who have severe focal organ disease, in whom the timing of infection is uncertain but this should be discussed with the paediatric infectious disease team. […] The evidence is limited for use in this group and duration of treatment should be discussed with an infectious disease specialist. […] Treatment should not be offered to babies with asymptomatic CMV or mild disease (1 or 2 transient or clinically insignificant signs or symptoms).

• #1 Congenital Cytomegalovirus Infection: Update on Diagnosis and Treatment

  https://www.mdpi.com/2076-2607/8/10/1516

  Valganciclovir is reserved for congenitally-infected neonates with the symptomatic disease at birth, such as microcephaly, intracranial calcifications, abnormal cerebrospinal fluid index, chorioretinitis, or sensorineural hearing loss. […] Treatment with antiviral drugs is not routinely recommended for neonates with the mildly symptomatic disease at birth, for neonates under 32 weeks of gestational age, or for infants more than 30 days old because of insufficient evidence from studies. […] However, since these populations represent the vast majority of neonates and infants with cCMV infection and they are at risk of developing late-onset sequelae, a biomarker able to predict long-term sequelae should also be found to justify starting treatment and reducing the burden of CMV-related complications.

• #1 Comprehensive CMV Testing: Assessing, Treating, and Managing Cytomegalovirus

  https://www.eurofins-viracor.com/news-and-events/posts/2023/july/comprehensive-cmv-testing-assessing-treating-and-managing-cytomegalovirus/

  Comprehensive CMV testing facilitates early detection of CMV infections, allowing for timely intervention. This is particularly crucial in high-risk populations, such as pregnant women and immunocompromised patients. Early identification of CMV in pregnant women enables appropriate counseling, monitoring, and potential interventions to reduce the risk of vertical transmission and associated fetal complications. […] Regular monitoring of CMV through comprehensive testing allows healthcare providers to detect viral reactivation or new infections early on. This enables proactive management, including antiviral treatment initiation or adjustment, to prevent or minimize CMV-related complications and improve overall patient outcomes. […] If CMV infection is suspected in a pregnant woman, diagnostic tests such as serology (testing for the presence of CMV antibodies) or polymerase chain reaction (PCR) testing can be performed to confirm the infection.

• #1 Comprehensive CMV Testing: Assessing, Treating, and Managing Cytomegalovirus

  https://www.eurofins-viracor.com/news-and-events/posts/2023/july/comprehensive-cmv-testing-assessing-treating-and-managing-cytomegalovirus/

  The management of CMV in pregnant women depends on various factors, including the timing of infection during pregnancy and the presence of symptoms. In cases of primary CMV infection during pregnancy, antiviral therapy may be considered to reduce the risk of transmission to the fetus. […] Close monitoring of CMV viral load and immune function is essential in transplant recipients. Regular laboratory testing and clinical follow-up are necessary to detect CMV infection or disease early and adjust the treatment accordingly. […] Antiviral therapy plays a critical role in the management of CMV infection. It helps to control viral replication, reduce symptoms, and prevent or treat complications associated with CMV. The goals of antiviral therapy for CMV may include preventing CMV disease, treating active CMV infections that cause symptoms or organ dysfunction, and maintenance therapy to prevent CMV disease recurrence or reactivation.

• #1 Decoding human cytomegalovirus for the development of innovative diagnostics to detect congenital infection | Pediatric Research

  https://www.nature.com/articles/s41390-023-02957-9

  A critical need remains for developing a highly sensitive, inexpensive, and rapid diagnostic to identify neonates with cCMV. […] More extensive population-based studies and universal screening initiatives are required to correctly define the effects of cCMV and determine if any intervention would prevent or attenuate observed impairments once detected.

• #1 Decoding human cytomegalovirus for the development of innovative diagnostics to detect congenital infection | Pediatric Research

  https://www.nature.com/articles/s41390-023-02957-9

  The gold standard for diagnosing fetal HCMV infection is the detection of viral DNA in the amniotic fluid via amniocentesis after the 21st week of gestation and at least six weeks after a maternal lytic infection. […] Detecting cytomegalovirus in culture or HCMV DNA in the blood, urine, saliva, or cerebrospinal fluid (CSF) within the first three weeks of life is necessary to diagnose a congenital infection. […] Technologies that incorporate NAAT-based approaches can be qualitative (detection of CMV only or yes/no answer) or quantitative (CMV detection with calculation of viral load). […] Emerging diagnostics promise the ability to not only rapidly identify HCMV DNA from multiple tissue matrices but also provide information regarding the cytomegalovirus strain(s) and antiviral resistance pattern(s) through ultrasensitive detection of single nucleotide-level modifications of the viral genome that are simultaneously analyzed by artificial intelligence algorithms.

• #1 Diagnosis of cytomegalovirus infection from clinical whole genome sequencing | Scientific Reports

  https://www.nature.com/articles/s41598-020-67656-5

  We sought to retrospectively detect the presence of CMV in patients undergoing rWGS and to identify those in whom CMV may have contributed to the severity of their illness. […] The ability of clinicians to identify active CMV viremia clinically can therefore be challenging. […] Current diagnostic approaches are inadequate to identify CMV infection in vulnerable patients in a timely manner. […] The use of unaligned reads from rWGS testing offers a cost-effective approach to identifying infectious pathogens while simultaneously testing for pathogenic variants in the host genome. […] Analyzing rWGS for microbial DNA enables the testing laboratory to alert clinicians in a timely manner to the presence of this pathogen while simultaneously evaluating the host genome for other pathogenic conditions. […] This approach has the potential to identify clinically relevant pathogens such as CMV, which may cause significant disease in certain vulnerable patient populations.

• #2 Cytomegalovirus (CMV) Antibodies, IgG, Serum » Incyte Diagnostics

  https://www.incytediagnostics.com/laboratory-services/test-directory/TestDetails/cytomegalovirus-cmv-antibodies-igg-serum

  Useful for determining whether a patient (especially transplant recipients, organ and blood donors) has had a recent infection or previous exposure to cytomegalovirus […] Sera drawn very early during the acute stage of infection may have undetectable levels of cytomegalovirus (CMV) IgG. The CMV IgG assay should not be used alone to diagnose CMV infection. Results should be considered in conjunction with clinical presentation, patient history, and other laboratory findings. In cases of suspected disease, submit a second specimen for testing in 10 to 14 days […] The performance characteristics of this assay have not been evaluated in immunosuppressed or organ transplant recipients and have not been established for cord blood or for testing of neonates […] Immune complexes or other immunoglobulin aggregates present in patient samples may cause increased nonspecific binding and produce false-positive results […] Potential cross-reactivity for CMV with human chorionic gonadotropin, HIV IgG, multiple myeloma IgG, rheumatoid factor IgM, and Toxoplasma gondii IgG have not be ruled out.

• #2 Cytomegalovirus (CMV): Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/215702-overview

  CMV has been detected via culture, serologies, antigen assays, polymerase chain reaction (PCR), and cytopathology. In the transplant population, antigen assays or PCR is used (sometimes in conjunction with cytopathology) for diagnosis and treatment determinations. […] The diagnosis of CMV pneumonia can be suggested by chest radiography findings, but these findings cannot be used to differentiate between other common causes of pneumonia in immunocompromised hosts. A chest radiograph finding consistent with pneumonia and a bronchoalveolar lavage (BAL) result that is CMV positive is a common method for diagnosis. […] Infection is defined as isolation of CMV, its viral proteins, or its nucleic acid from any tissue sample or body fluid. […] Clinically significant CMV disease (reactivation of previously latent infection or newly acquired infection) frequently develops in patients immunocompromised by HIV infection, solid-organ transplantation, or bone marrow transplantation, as well as in those receiving high-dose steroids, tumor necrosis antagonists, or other immunosuppressing medications for conditions such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Crohn disease, or psoriasis, among others.

• #2 Cytomegalovirus – Serology including Avidity | Public Health Ontario

  https://www.publichealthontario.ca/en/Laboratory-Services/Test-Information-Index/Cytomegalovirus-Serology

  CMV serology is most often indicated for diagnosing acute/recent CMV infection, determining evidence of past (latent) infection, and working up infants with suspected congenital infection. […] When CMV infection is suspected in a pregnant woman and suspected congenital CMV in a newborn infant, order CMV serology and submit a urine sample for CMV PCR testing. On the PHO requisition form, be sure to request both CMV IgM and IgG. Include all relevant clinical information (e.g. pregnancy, suspected congenital infection, etc.), onset date and signs and symptoms. […] CMV IgG avidity is both a sensitive and specific method for identifying pregnant women with recent primary CMV infection and thus at increased risk for vertical CMV transmission. The test is automatically conducted at PHOs laboratory for pregnant patients with a positive CMV IgG and IgM serology test ordered.

• #2 Cytomegalovirus (CMV) Infection: Symptoms, Treatment, Pregnancy

  https://www.medicinenet.com/cytomegalovirus_cmv/article.htm

  Diagnosis of cytomegalovirus […] Most CMV infections go undiagnosed because the virus usually causes little to no symptoms. When a person is infected with CMV, antibodies (proteins) to the virus called IgM and/or IgG anti-CMV antibodies develop and stay in the body for the rest of the person’s life. A blood test to detect the antibodies will be positive if the person has had a CMV infection. If the antibody test is negative, the person is considered to be uninfected with CMV. […] If a „definitive” diagnosis of active CMV infection is necessary, the virus can be found in bodily fluids (such as blood, saliva, or urine) or body tissues by culturing (growing) the virus or detecting its DNA or specific protein called pp65 antigen by PCR tests. These tests are done if a person has signs and symptoms consistent with an active CMV infection. The virus can become reactivated from its latent state (latent infection) when a person’s immune system has weakened. Tissue biopsy of affected body systems may sometimes show clumps of CMV in the cells, called „inclusion bodies.” CMV inclusion bodies make the infected cell look like an „owl’s eye” under the microscope. […] These tests may be done if a woman develops symptoms of CMV infection during pregnancy in order to provide counseling and possible treatment for congenital CMV. They may also be done to diagnose a congenital CMV infection if CMV is detected in a newborn’s urine, saliva, blood, or other body tissues within two to three weeks after birth.

• #2 Cytomegalovirus (CMV) Antibodies, IgM, Serum » Incyte Diagnostics

  https://www.incytediagnostics.com/laboratory-services/test-directory/TestDetails/cytomegalovirus-cmv-antibodies-igm-serum

  Immune complexes or other immunoglobulin aggregates present in patient samples may cause increased nonspecific binding and produce false-positive results. […] Potential cross-reactivity for CMV IgM may occur with specimens positive for Epstein-Barr virus viral capsid antigen IgM and parvovirus B19 IgM.

• #2 Decoding human cytomegalovirus for the development of innovative diagnostics to detect congenital infection | Pediatric Research

  https://www.nature.com/articles/s41390-023-02957-9

  Cytomegalovirus is the most common cause of congenital infectious disease and the leading nongenetic etiology of sensorineural hearing loss. […] The resulting financial and social burdens of congenital cytomegalovirus infection have led many medical centers to initiate targeted testing after birth, with a growing advocacy to advance universal newborn screening. […] This Review will detail our current understanding of congenital cytomegalovirus infection, while focusing our discussion on routine and emerging diagnostics for viral detection, quantification, and long-term prognostication. […] This submission discusses currently available cytomegalovirus diagnostics and introduces emerging platforms that promise improved sensitivity, specificity, limit of detection, viral quantification, detection of genomic antiviral resistance, and infection staging (primary, latency, reactivation, reinfection).

• #2

  https://www.healthychildren.org/English/health-issues/conditions/infections/Pages/Cytomegalovirus-CMV-Infections.aspx

  To diagnose a CMV infection, a pediatrician or other health care clinician may order lab tests of urine, saliva, blood or other body fluids. […] Fortunately, most children with CMV do not need treatment. Medical treatment is recommended for newborns with congenital CMV who have signs of illness. Even with treatment, babies with CMV infection may have or develop hearing changes or other developmental challenges. […] Serious CMV infections in children with immune system compromise, such as those with HIV infection or an organ transplant, can be treated with a medicine called ganciclovir or valganciclovir. This medicine is also used to treat newborns with moderate or severe congenital CMV disease.

• #2 Cytomegalovirus (CMV) in Pregnancy | ACOG

  https://www.acog.org/clinical-information/physician-faqs/cytomegalovirus-in-pregnancy

  Routine serologic screening of pregnant individuals for CMV is not recommended. The vast majority (approximately 90%) of positive IgM results are false positive and likely due to cross-reactivity with other non-CMV antibodies. The limitations of maternal IgM antibody screening in differentiating primary from recurrent infection also make the results difficult to use in counseling patients about fetal risk. […] Most adult CMV infections are asymptomatic, which makes recognition of primary infection difficult. Cytomegalovirus infection in adults usually is established by serologic testing. Serum samples collected 3-4 weeks apart, tested in parallel for anti-CMV IgG, are pathognomonic for the diagnosis of primary infection. Seroconversion from negative to positive or a significant increase (greater than fourfold [eg, from 1:4 to 1:16]) in anti-CMV IgG titers is evidence of infection.

• #2 Laboratory Testing for CMV and Congenital CMV | Cytomegalovirus (CMV) and Congenital CMV Infection | CDC

  https://www.cdc.gov/cytomegalovirus/php/laboratories/index.html

  The enzyme-linked immunosorbent assay is the most common serologic test for measuring antibody to CMV. […] Congenital CMV infection cannot be diagnosed with antibody testing (IgG and IgM). […] The standard laboratory test for diagnosing congenital CMV infection is a PCR on saliva, with a confirmatory test on urine. […] Polymerase chain reaction (PCR) on saliva is the standard laboratory test for diagnosing congenital CMV infection. Urine is usually collected and tested for confirmation. […] Currently, testing of newborns for CMV is not routinely performed, though some states perform targeted CMV testing of newborns who fail the hearing screening. […] A positive test for CMV IgG indicates that a person was infected with CMV at some time during their life but does not indicate when a person was infected.

• #3 Cytomegalovirus (CMV) Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/215702-workup

  Antigenemia is defined as the detection of the CMV pp65 antigen in leukocytes. […] The pp65 assay is used to detect messenger matrix proteins on the CMV virus, with either immunofluorescence assay or messenger RNA amplification. These proteins typically are expressed only during viral replication. Antigen tests often are the basis for institution of antiviral therapy in transplant recipients and may allow for the detection of subclinical disease in high-risk patients. The assay is sensitive and specific and yields results quickly. […] In immunocompromised patients, low or moderate CMV antigenemia may indicate reactivation or infection. […] It has been reported that the pp65 antigen assay and quantitative CMV PCR yield similar effectiveness in diagnosing and monitoring patients with active CMV infection.

• #4 Decoding human cytomegalovirus for the development of innovative diagnostics to detect congenital infection | Pediatric Research

  https://www.nature.com/articles/s41390-023-02957-9

  An overview of current and emerging diagnostics is provided in Table 2. […] Viral cultures, employing fibroblast monolayers, are also used in clinical laboratories. […] FDA-approved commercially available NAAT kits are listed in Table 3. […] Saliva is collected by oral (not throat) swab and is usually more convenient to obtain than urine in the first 24 hours of life, as urine production is limited. […] Digital PCR (dPCR) maybe a more precise, reproducible, and quantifiable assay than real-time quantitative PCR (qPCR), especially in samples with low viral load. […] While routine monitoring of viral burden is not currently advocated for neonates with moderate to severe symptomatic cCMV disease treated with ganciclovir (GCV) or valganciclovir (VGCV) for less than six months, recent investigations have reported antiviral resistance with prolonged courses (6 months).

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