Criteria

Definitions of CMV infection and disease in transplant recipients[41][48]​​

  • Cytomegalovirus (CMV) infection:

    • Defined as isolation of the CMV virus or detection of viral proteins or nucleic acid in any body fluid or tissue specimen.

  • Recurrent infection:

    • Defined as new detection of CMV in a patient who has had previously documented infection and who has not had virus detected on two consecutive tests usually a week apart.

  • Reinfection:

    • Defined as detection of a CMV strain that is distinct from the strain that was the cause of the original infection. Note that strain typing is not done outside research.

  • CMV syndrome:

    • Denotes the presence of significant malaise and/or fever often accompanied by bone marrow suppression. Other pathogens should be excluded.

    • In solid organ transport recipients, CMV syndrome is defined by the presence of fever and/or malaise, leukopenia, and thrombocytopenia.

  • CMV pneumonitis:

    • Defined by the presence of signs and/or symptoms of pulmonary disease combined with the detection of CMV in bronchoalveolar lavage fluid or lung tissue samples.

  • CMV gastrointestinal disease:

    • Defined by identification of clinical symptoms, findings of macroscopic mucosal lesions on endoscopy, and demonstration of CMV (by culture, histopathology, immuno-histochemical analysis, or in situ hybridisation) in a gastrointestinal tract biopsy specimen.

  • CMV hepatitis:

    • Defined by findings of elevated bilirubin and/or enzyme levels, absence of other documented cause of hepatitis, and detection of CMV (by culture, histopathology, immuno-histochemical analysis, or in situ hybridisation) in a liver biopsy specimen.

  • CMV retinitis:

    • Typical lesions must be confirmed by an ophthalmologist for the diagnosis of CMV retinitis.

Definitions of resistant and refractory CMV infection and disease in transplant recipients[49]

The following definitions for refractory and resistant CMV infection and disease in transplant recipients are proposed by the CMV Resistance Working Group of the CMV Drug Development Forum, for use in clinical trials.[49]

  • Refractory CMV infection

    • Defined as CMV viraemia that increases after at least 2 weeks of appropriately-dosed antiviral therapy.

  • Probably refractory CMV infection

    • Persistent viral load after at least 2 weeks of appropriately-dosed antiviral therapy.

  • Refractory CMV end-organ disease

    • Worsening signs and symptoms or progression into end-organ disease after at least 2 weeks of appropriately-dosed antiviral therapy.

  • Probable refractory CMV end-organ disease

    • Lack of improvement in signs and symptoms after at least 2 weeks of appropriately-dosed antiviral drugs.

  • Antiviral drug resistance

    • Viral genetic alteration that decreases susceptibility to one or more antiviral drugs.

Congenital Cytomegalovirus (cCMV) Infection and Disease: 2024 Case Definition[50]

​Clinical Criteria:

  • Neonatal Presentation:

    • At least one of the following during the neonatal period:

      • Hepatomegaly

      • Splenomegaly

      • Petechial rash or purpura (commonly referred to as 'blueberry muffin rash')

    • Child Aged ≤6 Years:

      • One or more of the following permanent conditions:

      • Microcephaly, defined as head circumference >2 standard deviations below the mean for age and sex

      • Brain imaging abnormalities indicative of cCMV (intracranial calcifications, periventricular calcifications, leukomalacia, polymicrogyria, lissencephaly, pachygyria, schizencephaly, ventriculomegaly)

      • Sensorineural hearing loss

      • Seizures

      • Cerebral palsy

      • Chorioretinitis

      • Vision impairment linked to CMV (retinitis, retinal scarring, optic neuritis, optic atrophy, cortical vision impairment)

  • Laboratory Criteria:

    • Confirmatory Laboratory Evidence:

      • No negative test (CMV DNA by NAAT or culture) on a urine sample within 21 days of life AND

      • Detection of CMV DNA by NAAT from urine, whole blood, or cerebrospinal fluid (CSF) within 21 days of life OR

      • Isolation of CMV in viral culture from urine, whole blood, or CSF within 21 days of life OR

      • Detection of CMV antigen by immunohistochemistry (IHC) or antigenaemia test in whole blood within 21 days of life

    • Presumptive Laboratory Evidence:

      • Similar criteria as confirmatory but includes saliva samples or tests conducted between 22 and 42 days of life

  • Case Classification:

    • Probable Case: Meets clinical criteria without laboratory confirmation

    • Confirmed Case: Meets both clinical and confirmatory laboratory criteria

  • Exclusion Criteria:

    • A more likely alternative diagnosis that explains the illness or findings

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