UK Standards for Microbiology Investigations
Cytomegalovirus Serology
Issued by the Standards Unit, Microbiology Services, PHE
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 1 of 21
© Crown copyright 2015
Cytomegalovirus Serology
Acknowledgments
UK Standards for Microbiology Investigations (SMIs) are developed under the
auspices of Public Health England (PHE) working in partnership with the National
Health Service (NHS), Public Health Wales and with the professional organisations
whose logos are displayed below and listed on the website https://www.gov.uk/ukstandards-for-microbiology-investigations-smi-quality-and-consistency-in-clinicallaboratories. SMIs are developed, reviewed and revised by various working groups
which are overseen by a steering committee (see
https://www.gov.uk/government/groups/standards-for-microbiology-investigationssteering-committee).
The contributions of many individuals in clinical, specialist and reference laboratories
who have provided information and comments during the development of this
document are acknowledged. We are grateful to the Medical Editors for editing the
medical content.
For further information please contact us at:
Standards Unit
Microbiology Services
Public Health England
61 Colindale Avenue
London NW9 5EQ
E-mail: standards@phe.gov.uk
Website: https://www.gov.uk/uk-standards-for-microbiology-investigations-smi-qualityand-consistency-in-clinical-laboratories
PHE Publications gateway number: 2015010
UK Standards for Microbiology Investigations are produced in association with:
Logos correct at time of publishing.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 2 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
Contents
ACKNOWLEDGMENTS .......................................................................................................... 2
AMENDMENT TABLE ............................................................................................................. 4
UK STANDARDS FOR MICROBIOLOGY INVESTIGATIONS: SCOPE AND PURPOSE ....... 5
SCOPE OF DOCUMENT ......................................................................................................... 8
SCREENING FLOWCHART .................................................................................................... 9
IMMUNOCOMPETENT HOST FLOWCHART ....................................................................... 10
PREGNANT WOMEN FLOWCHART .................................................................................... 12
CONGENITAL INFECTION FLOWCHART ........................................................................... 15
NOTIFICATION TO PHE OR EQUIVALENT IN THE DEVOLVED ADMINISTRATIONS ...... 18
REFERENCES ...................................................................................................................... 19
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 3 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
Amendment Table
Each SMI method has an individual record of amendments. The current amendments
are listed on this page. The amendment history is available from
standards@phe.gov.uk.
New or revised documents should be controlled within the laboratory in accordance
with the local quality management system.
Amendment No/Date.
4/27.04.15
Issue no. discarded.
2.6
Insert Issue no.
3
Section(s) involved
Amendment
Whole document.
Hyperlinks updated to gov.uk.
Page 2.
Updated logos added.
Whole document.
Whole document re-written and re-organised.
Scope.
Scope added to the document.
Flowchart.
Flowchart separated into four flowcharts for
serology in screening, immunocompetent host,
pregnant women and congenital infection.
Footnotes.
Extensive footnotes included for each of the above
flowcharts.
References.
References updated.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 4 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
UK Standards for Microbiology Investigations:
Scope and Purpose
Users of SMIs

SMIs are primarily intended as a general resource for practising professionals
operating in the field of laboratory medicine and infection specialties in the UK.

SMIs provide clinicians with information about the available test repertoire and
the standard of laboratory services they should expect for the investigation of
infection in their patients, as well as providing information that aids the
electronic ordering of appropriate tests.

SMIs provide commissioners of healthcare services with the appropriateness
and standard of microbiology investigations they should be seeking as part of
the clinical and public health care package for their population.
Background to SMIs
SMIs comprise a collection of recommended algorithms and procedures covering all
stages of the investigative process in microbiology from the pre-analytical (clinical
syndrome) stage to the analytical (laboratory testing) and post analytical (result
interpretation and reporting) stages.
Syndromic algorithms are supported by more detailed documents containing advice
on the investigation of specific diseases and infections. Guidance notes cover the
clinical background, differential diagnosis, and appropriate investigation of particular
clinical conditions. Quality guidance notes describe laboratory processes which
underpin quality, for example assay validation.
Standardisation of the diagnostic process through the application of SMIs helps to
assure the equivalence of investigation strategies in different laboratories across the
UK and is essential for public health surveillance, research and development activities.
Equal Partnership Working
SMIs are developed in equal partnership with PHE, NHS, Royal College of
Pathologists and professional societies.
The list of participating societies may be found at https://www.gov.uk/uk-standards-formicrobiology-investigations-smi-quality-and-consistency-in-clinical-laboratories.
Inclusion of a logo in an SMI indicates participation of the society in equal partnership
and support for the objectives and process of preparing SMIs. Nominees of
professional societies are members of the Steering Committee and Working Groups
which develop SMIs. The views of nominees cannot be rigorously representative of
the members of their nominating organisations nor the corporate views of their
organisations. Nominees act as a conduit for two way reporting and dialogue.
Representative views are sought through the consultation process.
SMIs are developed, reviewed and updated through a wide consultation process.

Microbiology is used as a generic term to include the two GMC-recognised specialties of Medical Microbiology (which includes
Bacteriology, Mycology and Parasitology) and Medical Virology.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 5 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
Quality Assurance
NICE has accredited the process used by the SMI Working Groups to produce SMIs.
The accreditation is applicable to all guidance produced since October 2009. The
process for the development of SMIs is certified to ISO 9001:2008.
SMIs represent a good standard of practice to which all clinical and public health
microbiology laboratories in the UK are expected to work. SMIs are NICE accredited
and represent neither minimum standards of practice nor the highest level of complex
laboratory investigation possible. In using SMIs, laboratories should take account of
local requirements and undertake additional investigations where appropriate. SMIs
help laboratories to meet accreditation requirements by promoting high quality
practices which are auditable. SMIs also provide a reference point for method
development.
The performance of SMIs depends on competent staff and appropriate quality
reagents and equipment. Laboratories should ensure that all commercial and in-house
tests have been validated and shown to be fit for purpose. Laboratories should
participate in external quality assessment schemes and undertake relevant internal
quality control procedures.
Patient and Public Involvement
The SMI Working Groups are committed to patient and public involvement in the
development of SMIs. By involving the public, health professionals, scientists and
voluntary organisations the resulting SMI will be robust and meet the needs of the
user. An opportunity is given to members of the public to contribute to consultations
through our open access website.
Information Governance and Equality
PHE is a Caldicott compliant organisation. It seeks to take every possible precaution
to prevent unauthorised disclosure of patient details and to ensure that patient-related
records are kept under secure conditions.
The development of SMIs are subject to PHE Equality objectives
https://www.gov.uk/government/organisations/public-health-england/about/equalityand-diversity. The SMI Working Groups are committed to achieving the equality
objectives by effective consultation with members of the public, partners, stakeholders
and specialist interest groups.
Legal Statement
Whilst every care has been taken in the preparation of SMIs, PHE and any supporting
organisation, shall, to the greatest extent possible under any applicable law, exclude
liability for all losses, costs, claims, damages or expenses arising out of or connected
with the use of an SMI or any information contained therein. If alterations are made to
an SMI, it must be made clear where and by whom such changes have been made.
The evidence base and microbial taxonomy for the SMI is as complete as possible at
the time of issue. Any omissions and new material will be considered at the next
review. These standards can only be superseded by revisions of the standard,
legislative action, or by NICE accredited guidance.
SMIs are Crown copyright which should be acknowledged where appropriate.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 6 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
Suggested Citation for this Document
Public Health England. (2015). Cytomegalovirus Serology. UK Standards for
Microbiology Investigations. V 28 Issue 3. https://www.gov.uk/uk-standards-formicrobiology-investigations-smi-quality-and-consistency-in-clinical-laboratories
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 7 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
Scope of Document
Type of specimen
Blood, serum, plasma, urine, saliva, amniotic fluid
Scope
Cytomegalovirus (CMV) is a common infection that is usually harmless. It can cause
serious disease in immunocompromised individuals and in babies who were infected
in utero. The present SMI is composed of four algorithms that cover the investigation
of CMV infection status in the following situations:

screening of blood/organ donors, and of individuals at risk of CMV disease1,2

diagnosing CMV infection in symptomatic immunocompetent individuals (nonpregnant)

diagnosing CMV infection in pregnant women

diagnosing congenital infection
This 'CMV serology' SMI does not cover the diagnosis of CMV infection in
immunocompromised individuals (including HIV-infected, graft recipient,
immunosuppressive treatment). Molecular assays (or pp65 antigenemia) are preferred
for diagnosis and monitoring of CMV infection and related disease in this patient type.
CMV belongs to the Herpesviridae family and persists in the host as a life-long latent
infection. After primary infection, the endogenous virus may replicate de novo causing
a reactivation. A new infection with an exogenous CMV can occur, referred to as
reinfection3,4. In all settings the infection is usually asymptomatic in the
immunocompetent host; however, some primary infections result in a mononucleosis
syndrome or mild flu-like symptoms.
CMV is the most common cause of congenital infection, with approximately 0.5% of
neonates infected5. Most congenital infections are asymptomatic, with only 10 - 15% of
neonates exhibiting clinical signs, such as intrauterine growth retardation,
microcephaly, hepatosplenomegaly, petechiae and jaundice. Ninety percent of
children with symptomatic infection, and 10 - 15% of those with asymptomatic
infection, develop one or more long-term neurological sequelae such as mental
retardation, psychomotor retardation, sensorineural hearing loss (SNHL), and eye
abnormalities.
Definitions
For all antigen, antibody and NAATs testing the following definitions apply:
Reactive – Initial internal-stage positive result pending confirmation.
Not reactive– Initial internal-stage negative result.
Detected – Report-stage confirmed reactive result.
Not detected – Report-stage not reactive result.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 8 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
Screening Flowchart
Determination of CMV IgG
status as part of a care
pathway
a, b, c
CMV IgG
d, e
Reactive
Not reactive
Report:
CMV infection at some
Report:
No evidence of past
CMV infection
time
f
Please note: Equivocal results are not included in the above algorithm.
Footnotes Relating to Screening Flowchart
a) This includes blood/organ donors and individuals at risk of CMV disease1.
Screening of gametes/embryo donors is not a mandatory requirement6.
b) Individuals at risk of CMV disease include future graft recipients and individuals
receiving (or due to receive) immunosuppressive treatment. CMV IgG antibody
is one of the markers required to evaluate the risk of CMV infection or
reactivation, and to implement appropriate control measures and pre-emptive
or preventive treatment.
c) Breast milk donors are no longer screened as there is evidence that
pasteurisation and other processing techniques, including freezing, destroys
contamination7.
d) Be aware of possible passively acquired antibody. It is not recommended to
screen for CMV IgG in patients who have recently received blood or blood
products, including anti-D immunoglobulins. Passively acquired CMV IgG may
lead to misinterpretation of the CMV infection status and to false seropositive or
seroconversion results. Passively acquired immunoglobulins decrease over
time, with a half-life of approximately 3 weeks. If this data is not available at the
time of transplantation the worst case scenario must be considered in terms of
preventing CMV infection.
e) Consider the use of two assays for transplant patients1.
f) The detection of CMV IgG in blood and organ donors indicates potential
infectivity of donations.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 9 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
Immunocompetent Host Flowchart
Potential CMV-related illness in
a, b
immunocompetent individuals
CMV IgM
Not reactive
Reactive
c, d
CMV IgG
Not reactive
e, f
g
Reactive
REPORT:
CMV IgM detected, CMV IgG not detected.
Repeat CMV IgG testing in 1 to 3 weeks to
h
further investigate possible CMV infection
CMV IgG
f
Not reactive
Reactive
REPORT: No evidence
of recent CMV infection
REPORT: Evidence of
recent primary
CMV infection
REPORT: Suggestive
of recent CMV infection
Report/notify case
Please note: Equivocal results are not included in the above algorithm.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 10 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
h, i, j, k
Cytomegalovirus Serology
Footnotes Relating to Immunocompetent Host Flowchart
a) Clinical mononucleosis, fever, hepatitis or myalgia of unknown origin in
immunocompetent individuals.
b) Immunocompetent women: where possible query pregnancy. If pregnant, refer
to the algorithm for pregnant women.
c) The presence of CMV IgM may indicate one of the following:

primary infection

re-infection

reactivation

false-positive test result
Therefore the presence of CMV IgM cannot be used independently to diagnose
primary CMV infection.
d) Consider excluding false positive CMV IgM due to acute EBV infection by
testing for heterophile antibody or EBV VCA-IgM. Refer to V 26 - Epstein-Barr
Virus Serology.
e) Consider testing CMV IgG and IgM on an earlier sample, if available, to aid
interpretation.
f) Infants (<12 months): passively acquired maternal IgG may be present.
Determine the maternal IgG status and, if positive, consider testing for CMV in
the infant’s blood and/or urine. Refer to the algorithm for congenital infection if
required8,9.
g) Consider CMV NAAT on the existing serum or plasma sample. A positive CMV
NAAT indicates primary CMV infection. If the CMV NAAT is negative, primary
CMV infection is unlikely but cannot be excluded, and the CMV IgG test should
be repeated within 1 to 3 weeks.
h) Review level of IgM reactivity and interpret results according to local assay
experience.
i) Recent infection includes primary infection, reinfection and reactivation.
j) Consider IgG avidity testing on the existing serum sample, especially where
timing of primary infection is important eg pregnancy (refer to the algorithm for
pregnant women).
k) Where available, consider testing an earlier sample for IgG and IgM to
differentiate between primary and secondary infection.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 11 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
Pregnant Women Flowchart10-17
Suspicion of primary infection in a
a
pregnant woman
CMV
IgM
Not reactive
Reactive
REPORT: No evidence
of recent primary CMV
e
infection
Not reactive
b, c
Reactive
Test earlier sample if available for
CMV IgG and IgM
d
CMV IgG
IgG Reactive
IgM Reactive
IgG Reactive
IgM Not reactive
CMV IgG
h
avidity
REPORT: No evidence of
recent primary CMV infection.
Reactivation or re-infection cannot
e, i
be excluded
IgG Not reactive
IgM Not reactive
IgG Not reactive
IgM Reactive
Not reactive
f, g
REPORT: CMV IgM detected,
CMV IgG not detected. Repeat
CMV IgG testing in 3 weeks to
further investigate possible CMV
infection
CMV IgG
High
l
Low
m
Repeat
avidity in
three weeks
REPORT: No evidence of recent
primary CMV infection in the past
three months. Reactivation or ree
infection cannot be excluded
Reactive
Repeat IgG and
IgM on the same
sample to confirm
seroconversion
Intermediate
Rise
REPORT: Consistent
with recent primary CMV
j, k
infection
Report/notify case
Refer to congenital infection algorithm
Please note: Equivocal results are not included in the above algorithm
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 12 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
n
REPORT: Recent
CMV infection cannot
be excluded
Stable
REPORT: Evidence of
recent primary CMV
infection at the time of the
j, k
earlier sample
Cytomegalovirus Serology
Footnotes Relating to Pregnant Women Flowchart
a) CMV infection should be suspected in symptomatic pregnant women
presenting with clinical mononucleosis, fever, hepatitis or myalgia of unknown
origin. If the woman is asymptomatic but concerns arise due to the foetus, refer
to the congenital infection algorithm.
b) The presence of CMV IgM may indicate one of the following:

primary infection

re-infection

reactivation

false-positive test result
Therefore, the presence of CMV IgM cannot be used by itself to diagnose
primary CMV infection.
c) Consider excluding false positive CMV IgM due to concurrent EBV acute
infection by testing for heterophile antibody or EBV VCA-IgM V 26 – EpsteinBarr Virus Serology.
d) Laboratories referring the sample for avidity testing may issue an interim report:
‘Suggestive of recent CMV infection. CMV IgG avidity result will follow. Please
send another sample in 3 weeks’ time.’
e) Seek alternative causes which present with similar illness in pregnancy.
f) Those laboratories not performing NAAT can ask for a repeat serology sample.
g) Consider NAAT on blood or urine sample.
h) Low avidity index is associated with high risk of congenital infection, whilst high
avidity index detected in the first trimester of gestation is associated with low
risk of vertical transmission17-20. If an earlier sample is available, test both
samples (or the earlier sample only) for avidity. Increasing avidity results over
time confirms acute infection around the time of the earlier sample; persistent
low avidity results beyond 18 weeks (from the earliest sample tested) may be
due to lack of specificity, and may require further confirmation with a different
avidity assay21. CMV IgG avidity results cannot exclude or confirm a
reactivation or a re-infection.
i) Consider avidity testing on the earlier sample. Avidity is only recommended to
be interpreted in the context of an IgM positive result; however, some experts
may consider interpretation is possible where IgM is negative.
j) Risk of congenital infection is about 40%. Refer to fetal medicine. Congenital
infection can be confirmed prenatally by detecting CMV in amniotic fluid. For
optimal results amniocentesis must be performed at least 6 weeks after
presumed time of maternal infection and after 21 weeks of gestation22-24.
k) Investigate CMV infection in the new born baby: perform CMV NAAT in urine or
saliva within the first 3 weeks of life. Alternatively a positive blood CMV IgM can
confirm the infection however the test lacks sensitivity and NAAT should be
performed in case of negative result25. Refer to the algorithm for congenital
infection8,9.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 13 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
l) High avidity: no evidence of recent infection in the past 3 months12-16,26.
m) Low avidity indicates recent infection of usually less than 3 months prior to
sample date16.
n) Interpretation of intermediate avidity is difficult and recent/relatively recent
primary infection cannot be excluded, particularly in samples taken after the 1 st
trimester16,17.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 14 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
Congenital Infection Flowchart17,26
CMV IgG confirmed in maternal blood together with other evidence of
a
CMV infection in the mother (refer to pregnant woman algorithm)
Suspicion of
congenital infection
Antenatal diagnosis
b
Neonatal diagnosis
c, d
≤ 3 weeks of age
CMV in
amniotic fluid
g
(NAAT)
Reactive
m
CMV IgM
CMV in urine or saliva
within 3 weeks after birth
h
(Culture or NAAT)
Not reactive
Late diagnosis
f, d
>3 weeks of age
e
Reactive
>3 weeks & <12 months of age
>12 months of age
CMV in urine or saliva (Culture or
h, i, j, k, l
NAAT)
CMV IgG
Not reactive
Not reactive
Not reactive
Confirm with detection
of CMV in urine or
saliva or Guthrie card.
Not reactive
REPORT: Congenital
n
infection highly unlikely
Repeat testing
CMV in urine or
i, j, k
saliva
h, I, j, m, n
Repeat testing CMV in
k
urine or saliva
Not reactive
Reactive
Reactive
Confirm with repeat
testing on urine or saliva,
j, k, n
or Guthrie card
Not reactive
REPORT: Not consistent
with congenital infection
REPORT: Confirmed
o
congenital CMV infection
Report/notify case
Please note: Equivocal results are not included in the above algorithm.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 15 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
CMV in Guthrie
l
card
Reactive
Not reactive
REPORT: Congenital CMV infection
unlikely
REPORT: Congenital infection
n
cannot be excluded
Reactive
Cytomegalovirus Serology
Footnotes Relating to Congenital Infection Flowchart
a) Congenital CMV can be excluded if mother is CMV IgG negative. Congenital
CMV infection can result from both primary and recurrent maternal infection.
The risk of transmission is greater after primary infection (30-40%) than after
recurrent infection (~1%)27. Not all congenitally infected babies are
symptomatic at birth or develop sequelae (see Scope).
b) Antenatal diagnosis can be requested when there is suspicion of recent
maternal infection or when there are ultrasound features such as intrauterine
growth retardation, ventricular dilatation, intracranial calcification, microcephaly,
ascites, hepatomegaly, abdominal calcification, thickened placenta.
c) Neonatal diagnosis is requested when clinical signs suggestive of congenital
infection (such as intrauterine growth retardation, microcephaly,
hepatosplenomegaly, petechiae and jaundice) are present at, or prior to, birth.
It is also indicated for those infants born to a mother with documented recent
infection, inconclusive results or with typical ultrasound abnormalities or when
amniocentesis was declined.
d) Detection of CMV by NAAT (in urine or saliva) within the first 3 weeks of life is
considered the gold standard method for the diagnosis of congenital CMV
infection.
e) If a suitable sample for NAAT is not available, CMV IgM can be tested in the
neonate’s blood. However, the test lacks sensitivity and NAAT should be
performed if the CMV IgM result is negative25.
f) Late diagnosis is requested for infants and young children, usually
asymptomatic at birth, who develop sequelae within a 5 to 7-year period such
as sensorineural hearing loss, mental retardation, delay of psychomotor
development and visual impairment28. The absence of CMV IgG in maternal
blood after delivery excludes congenital CMV as the cause of hearing loss or
other defect. The presence of CMV IgM in the booking blood supports, but does
not confirm the diagnosis of congenital CMV.
g) For optimal sensitivity, amniocentesis must be performed at a time that is at
least 6 weeks after presumed time of maternal infection and after 21 weeks of
gestation22-24.
h) Both urine and saliva of congenitally infected term neonates contain high levels
of CMV and have equivalent sensitivity for diagnosis29. Real time PCR
performed on dried saliva specimens was shown to be a highly sensitive and
practical tool to diagnose congenital CMV5. Reactive CMV NAAT on samples
taken after 3 weeks of age, cannot be distinguish congenital from postnatal or
perinatal infection (refer to the ‘late diagnosis’ branch of the algorithm).
i) Viral excretion in urine and saliva lasts for several years with a steep decline
after 5 years30. The median duration of urinary excretion assessed by culture
was estimated to be 4.55 years in children born with asymptomatic and 2.97
years in symptomatic children31. Although there is some evidence to suggest
that repeat testing should be carried out twice due to intermittent shedding,
local policy may dictate that repeat testing once is acceptable30.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 16 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
j) There is evidence to suggest that urine is superior to saliva when screening for
postnatal CMV infections in preterm infants using NAAT32.
k) If the result is discordant, investigate possible laboratory error and request a
third sample to confirm.
l) CMV viral load is significantly lower in blood than in urine or saliva, and
sensitivity of NAAT performed from a dried blood spot (Guthrie card) has been
reported to be as low as 28%33,34.
m) Investigate CMV infection in the neonate if pregnancy continues.
n) Negative predictive values of between 92.7% and 95.7% are reported for CMV
NAAT assays of amniotic fluid were reported10.
o) All babies and children with a confirmed congenital CMV infection must be
followed up with regular paediatric examination and audiology assessment 35.
Symptomatic neonates with CNS disease and/or focal organ disease may
receive ganciclovir35. Treatment of neonates with neurological symptoms can
prevent developmental delays and hearing deterioration36,37.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 17 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
Notification to PHE38,39 or Equivalent in the Devolved
Administrations40-43
The Health Protection (Notification) regulations 2010 require diagnostic laboratories to
notify Public Health England (PHE) when they identify the causative agents that are
listed in Schedule 2 of the Regulations. Notifications must be provided in writing, on
paper or electronically, within seven days. Urgent cases should be notified orally and
as soon as possible, recommended within 24 hours. These should be followed up by
written notification within seven days.
For the purposes of the Notification Regulations, the recipient of laboratory
notifications is the local PHE Health Protection Team. If a case has already been
notified by a registered medical practitioner, the diagnostic laboratory is still required
to notify the case if they identify any evidence of an infection caused by a notifiable
causative agent.
Notification under the Health Protection (Notification) Regulations 2010 does not
replace voluntary reporting to PHE. The vast majority of NHS laboratories voluntarily
report a wide range of laboratory diagnoses of causative agents to PHE and many
PHE Health Protection Teams have agreements with local laboratories for urgent
reporting of some infections. This should continue.
Note: The Health Protection Legislation Guidance (2010) includes reporting of Human
Immunodeficiency Virus (HIV) & Sexually Transmitted Infections (STIs), Healthcare
Associated Infections (HCAIs) and Creutzfeldt–Jakob disease (CJD) under
‘Notification Duties of Registered Medical Practitioners’: it is not noted under
‘Notification Duties of Diagnostic Laboratories’.
https://www.gov.uk/government/organisations/public-health-england/about/ourgovernance#health-protection-regulations-2010
Other arrangements exist in Scotland40,41, Wales42 and Northern Ireland43.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 18 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
References
1. SaBTO Advisory Committee on the Safety of Blood,Tissues and Organs. Guidance on the
microbiological safety of human organs, tissues and cells used in transplantation. 2011 p. 1-60.
2. SaBTO Advisory Committee on the Safety of Blood,Tissues and Organs. Cytomegalovirus tested
blood components: Position Statement. 2012 p. 1-15.
3. Boppana SB, Rivera LB, Fowler KB, Mach M, Britt WJ. Intrauterine transmission of cytomegalovirus
to infants of women with preconceptional immunity. N Engl J Med 2001;344:1366-71.
4. Ross SA, Arora N, Novak Z, Fowler KB, Britt WJ, Boppana SB. Cytomegalovirus reinfections in
healthy seroimmune women. J Infect Dis 2010;201:386-9.
5. Boppana SB, Ross SA, Shimamura M, Palmer AL, Ahmed A, Michaels MG, et al. Saliva
polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N Engl J Med
2011;364:2111-8.
6. The Human Fertilisation and Embryology Authority. Code of Practice 8th Edition. 2013.
7. National Institute for Healthcare and Clinical Excellence. Donor milk banks: the operation of donor
milk bank services. 2010.
8. Ross SA, Novak Z, Pati S, Boppana SB. Overview of the diagnosis of cytomegalovirus infection.
Infect Disord Drug Targets 2011;11:466-74.
9. Manicklal S, Emery VC, Lazzarotto T, Boppana SB, Gupta RK. The "silent" global burden of
congenital cytomegalovirus. Clin Microbiol Rev 2013;26:86-102.
10. Enders G, Bader U, Lindemann L, Schalasta G, Daiminger A. Prenatal diagnosis of congenital
cytomegalovirus infection in 189 pregnancies with known outcome. Prenat Diagn 2001;21:362-77.
11. Numazaki Y, Yano N, Morizuka T, Takai S, Ishida N. Primary infection with human
cytomegalovirus: virus isolation from healthy infants and pregnant women. American Journal of
Epidemiology 1970;91:410-7.
12. Grangeot-Keros L, Mayaux MJ, Lebon P, Freymuth F, Eugene G, Stricker R, et al. Value of
cytomegalovirus (CMV) IgG avidity index for the diagnosis of primary CMV infection in pregnant
women. J Infect Dis 1997;175:944-6.
13. Revello MG, Gorini G, Gerna G. Clinical evaluation of a chemiluminescence immunoassay for
determination of immunoglobulin G avidity to human cytomegalovirus. Clin Diagn Lab Immunol
2004;11:801-5.
14. Lazzarotto T, Guerra B, Lanari M, Gabrielli L, Landini MP. New advances in the diagnosis of
congenital cytomegalovirus infection. J Clin Virol 2008;41:192-7.
15. Lagrou K, Bodeus M, Van Ranst M, Goubau P. Evaluation of the new Architect cytomegalovirus
immunoglobulin M (IgM), IgG, and IgG avidity assays. J Clin Microbiol 2009;47:1695-9.
16. Vauloup-Fellous C, Berth M, Heskia F, Dugua JM, Grangeot-Keros L. Re-evaluation of the VIDAS
(®) cytomegalovirus (CMV) IgG avidity assay: determination of new cut-off values based on the
study of kinetics of CMV-IgG maturation. J Clin Virol 2013;56:118-23.
17. Prince HE, Lape-Nixon M. Role of cytomegalovirus (CMV) IgG avidity testing in diagnosing primary
CMV infection during pregnancy. Clin Vaccine Immunol 2014;21:1377-84.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 19 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
18. Kanengisser-Pines B, Hazan Y, Pines G, Appelman Z. High cytomegalovirus IgG avidity is a
reliable indicator of past infection in patients with positive IgM detected during the first trimester of
pregnancy. J Perinat Med 2009;37:15-8.
19. Munro SC, Hall B, Whybin LR, Leader L, Robertson P, Maine GT, et al. Diagnosis of and screening
for cytomegalovirus infection in pregnant women. J Clin Microbiol 2005;43:4713-8.
20. Grangeot-Keros L, Mayaux MJ, Lebon P, Freymuth F, Eugene G, Stricker R, et al. Value of
cytomegalovirus (CMV) IgG avidity index for the diagnosis of primary CMV infection in pregnant
women. J Infect Dis 1997;175:944-6.
21. Lumley S, Patel M, Griffiths PD. The combination of specific IgM antibodies and IgG antibodies of
low avidity does not always indicate primary infection with cytomegalovirus. J Med Virol
2014;86:834-7.
22. Yinon Y, Farine D, Yudin MH, Gagnon R, Hudon L, Basso M, et al. Cytomegalovirus infection in
pregnancy. J Obstet Gynaecol Can 2010;32:348-54.
23. Grangeot-Keros L, Cointe D. Diagnosis and prognostic markers of HCMV infection. J Clin Virol
2001;21:213-21.
24. Bodeus M, Hubinont C, Bernard P, Bouckaert A, Thomas K, Goubau P. Prenatal diagnosis of
human cytomegalovirus by culture and polymerase chain reaction: 98 pregnancies leading to
congenital infection. Prenat Diagn 1999;19:314-7.
25. Revello MG, Zavattoni M, Baldanti F, Sarasini A, Paolucci S, Gerna G. Diagnostic and prognostic
value of human cytomegalovirus load and IgM antibody in blood of congenitally infected newborns.
J Clin Virol 1999;14:57-66.
26. Revello MG, Gerna G. Diagnosis and management of human cytomegalovirus infection in the
mother, fetus, and newborn infant. Clin Microbiol Rev 2002;15:680-715.
27. Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital
cytomegalovirus (CMV) infection. Rev Med Virol 2007;17:253-76.
28. NHS Screening Programmes. NHS Newborn Hearing Screening Programme. 2009.
29. Yamamoto AY, Mussi-Pinhata MM, Marin LJ, Brito RM, Oliveira PF, Coelho TB. Is saliva as reliable
as urine for detection of cytomegalovirus DNA for neonatal screening of congenital CMV infection?
J Clin Virol 2006;36:228-30.
30. Rosenthal LS, Fowler KB, Boppana SB, Britt WJ, Pass RF, Schmid SD, et al. Cytomegalovirus
shedding and delayed sensorineural hearing loss: results from longitudinal follow-up of children with
congenital infection. Pediatr Infect Dis J 2009;28:515-20.
31. Noyola DE, Demmler GJ, Williamson WD, Griesser C, Sellers S, Llorente A, et al. Cytomegalovirus
urinary excretion and long term outcome in children with congenital cytomegalovirus infection.
Congenital CMV Longitudinal Study Group. Pediatr Infect Dis J 2000;19:505-10.
32. Gunkel J, Wolfs TF, Nijman J, Schuurman R, Verboon-Maciolek MA, de Vries LS, et al. Urine is
superior to saliva when screening for postnatal CMV infections in preterm infants. J Clin Virol
2014;61:61-4.
33. de Vries JJ, Claas EC, Kroes AC, Vossen AC. Evaluation of DNA extraction methods for dried
blood spots in the diagnosis of congenital cytomegalovirus infection. J Clin Virol 2009;46 Suppl
4:S37-S42.
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 20 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England
Cytomegalovirus Serology
34. Boppana SB, Ross SA, Novak Z, Shimamura M, Tolan RW, Jr., Palmer AL, et al. Dried blood spot
real-time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus
infection. JAMA 2010;303:1375-82.
35. Kadambari S, Williams EJ, Luck S, Griffiths PD, Sharland M. Evidence based management
guidelines for the detection and treatment of congenital CMV. Early Hum Dev 2011;87:723-8.
36. Kimberlin DW, Lin CY, Sanchez PJ, Demmler GJ, Dankner W, Shelton M, et al. Effect of ganciclovir
therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central
nervous system: a randomized, controlled trial. J Pediatr 2003;143:16-25.
37. Oliver SE, Cloud GA, Sanchez PJ, Demmler GJ, Dankner W, Shelton M, et al. Neurodevelopmental
outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections
involving the central nervous system. J Clin Virol 2009;46 Suppl 4:S22-S26.
38. Public Health England. Laboratory Reporting to Public Health England: A Guide for Diagnostic
Laboratories. 2013. p. 1-37.
39. Department of Health. Health Protection Legislation (England) Guidance. 2010. p. 1-112.
40. Scottish Government. Public Health (Scotland) Act. 2008 (as amended).
41. Scottish Government. Public Health etc. (Scotland) Act 2008. Implementation of Part 2: Notifiable
Diseases, Organisms and Health Risk States. 2009.
42. The Welsh Assembly Government. Health Protection Legislation (Wales) Guidance. 2010.
43. Home Office. Public Health Act (Northern Ireland) 1967 Chapter 36. 1967 (as amended).
Virology | V 28 | Issue no: 3 | Issue date: 27.04.15 | Page: 21 of 21
UK Standards for Microbiology Investigations | Issued by the Standards Unit, Public Health England