Journal of Clinical Virology 103 (2018) 25–26

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Journal of Clinical Virology

journal homepage: www.elsevier.com/locate/jcv

Letter to the editor

T
Varicella Zoster Immunoglobulin G (VZIG)—Do current guidelines advocate overuse?

is lacking on waning natural immunity to VZV in the im-

To the editor,
munosuppressed population, although there are data showing waning
of VZV IgG in children with uncontrolled HIV over a period of years [4].
We recently coordinated a large Varicella-Zoster Virus (VZV) con-
Additionally it is difficult to know if the absence of high titres of VZV
tact screening exercise following a series of exposures to im-
IgG represents susceptibility to infection. Enzyme-linked Im-
munosuppressed patients in a renal transplant clinic. The index case
munosorbent Assays (ELISA) may not detect low titre of VZV IgG re-
was an immunosuppressed renal transplant patient and was seen in 3
liably, and cell-mediated immunity to VZV is not specifically tested at
renal transplant outpatient clinics with VZV vesicles on her face and
all, although is presumed to be diminished in those listed as ‘group B’
exposed parts of the body. As she spent time in the waiting room of the
immunosuppressed. Cell-mediated immunity is of greater importance in
clinics, comprised of an entirely immunosuppressed population, a large
risk of reactivation of herpesviruses in general and antibody testing can
contact tracing and screening exercise was initiated.
be thought of as a surrogate marker rather than a true test of immunity.
Recent Public Health England (PHE) guidelines [1] define im-
VZIG is a precious and expensive resource and unnecessary use
munosuppressed populations as ‘group A’ and ‘group B’. ‘Group B’ im-
should be avoided to preserve availability for high-risk contacts. In the
munosuppressed patients are those on treatment or completed treat-
UK VZIG costs £450 per vial, and with weight based administrations
ment within the last 6 months for acute lymphoblastic leukaemia; being
costs per patient often exceed £2000. Disseminated VZV infection in the
followed up for lymphoproliferative disorders; on immunosuppression
immunosuppressed population is a life threatening disease with high
for solid organ transplant currently or within the last 6 months; with
mortality. In 2016 there were a total of 16 deaths in the UK with
severe primary immunodeficiency (excluding those on IVIG); received a
Varicella listed as a cause (8 chickenpox, 1 varicella encephalitis, 2
haematopoietic stem cell transplant until at least 24 months post-
varicella pneumonia, and 5 varicella with complications) [5]. Although
transplant and 12 months off immunosuppression; received certain
specific data for mortality from varicella in the immunosuppressed is
monoclonal antibodies or cytokine inhibitors in the last 6 months; and
not available, it seems to be a rare event.
people with acquired immunodeficiency syndrome. ‘Group B’ im-
Antibody loss in the bone marrow transplant (BMT) population is
munosuppressed patients are unlikely to have developed or maintained
apparent, however study on the incidence of loss of natural immunity to
adequate antibody levels from prior infection or vaccination. If these
VZV in solid organ transplant and other immunosuppressed populations
patients are in contact with VZV, they require testing of VZV Im-
is needed. With the exception of BMT recipients, rapid loss of immunity
munoglobulin G (IgG) regardless of their previous VZV IgG results, or
over weeks to months in patients with recent strongly positive optical
history of chickenpox, and all contacts with a negative IgG (< 150 IU/
densities seems unlikely, and VZIG administration to such patients may
ml) should be administered Varicella-Zoster Immunoglobulin (VZIG)
reasonably be avoided. This approach may help to safely reduce VZIG
within 7 days of contact. If there is insufficient time left in the window
use compared to current recommendations.
for administration of VZIG to test for VZV IgG, then VZIG should be
Antivirals such as aciclovir together with VZIG have been used as
administered urgently without testing immunity.
post-exposure prophylaxis in neonates [6], but the use of aciclovir alone
Our index case was in close contact with a total of 38 patients over 3
in profoundly immunosuppressed patients is not recommended as per
clinics. 6 patients were identified as ‘Group B’ contacts with 24 h left in
the UK guidelines. However in situations where VZIG may not be
the window for VZIG administration, making re-testing of VZV IgG
available, commencing aciclovir from 7 to 14 days after exposure and
unfeasible. 1 patient was previously VZV IgG negative and so was ad-
continuing the course if VZV IgG levels are found to be ‘non-protective’
ministered VZIG urgently. As there was insufficient time for retesting,
may represent an alternative strategy in some cases [7].
urgent VZIG administration was also advised for the remaining 5 con-
tacts. All of these 5 patients had tested positive for VZV IgG in the past
Funding
with optical densities high into the positive range. For these 5 patients
the most recent strongly positive VZV IgG levels were seen 2 months, 4
None.
months, 7 months, 14 months, and 51 months back respectively. Repeat
testing of VZV IgG antibodies was done for 4 out of 5 of these patients
Conflict of interest
and showed that all 4 had titres of VZV IgG high into the protective
range at the time of exposure.
The authors do not have commercial or other associations that
The PHE guidelines are based on the premise of waning antibody, a
might pose a conflict of interest.
process which may be accelerated in the immunosuppressed popula-
tion. There are data showing waning vaccine-induced immunity to VZV
Ethical approval
in the immunocompetent [2] and in immunosuppressed populations [3]
over a period of years. However natural infection is thought to provoke
Not required.
a stronger and more durable antibody response than vaccination. Data

https://doi.org/10.1016/j.jcv.2018.03.007
Received 28 November 2017
1386-6532/ © 2018 Elsevier B.V. All rights reserved.
Letter to the editor Journal of Clinical Virology 103 (2018) 25–26

Acknowledgement
We would like to acknowledge Professor Paul Griffiths for his con-
tribution.
References
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⁎
David Harrington , Tanzina Haque
Department of Virology, Royal Free Hospital, Pond Street, London, NW3
2QG, United Kingdom
E-mail address: davidharrington@nhs.net

⁎
Corresponding author.

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