Correspondence
Zika virus: are we going
too far?
Because of the risk of sexual
transmission and reported persistence
of Zika virus RNA in semen, the Centers
for Disease Control and Prevention
has proposed a 6-month delay before
attempts at conception for all men
possibly exposed to Zika virus.
A correspondence published in 20161
suggests a potential transmission
through other body fluids. After
exposure, viral RNA has been detected
in urine and saliva for up to 91 days2
and in vaginal secretions for up to
14 days.3 Furthermore, infective viral
particles have also been isolated from
tears in an animal model. Therefore,
existing recommendations should also
include hygiene precautions to avoid
contact with body fluids for pregnant
women and couples contemplating
conception. Importantly, these
recommendations should be applied
to any person that has travelled to
areas with active Zika virus circulation,
as well as those living in endemic
regions, and might be quite restricting.
Thus, are we not going too far?
If referring to cytomegalovirus, which
remains the most common congenital
infection affecting approximately 0·7%
of newborns, and the leading cause
of non-genetic neurodevelopmental
disabilities in children, its transmission
also occurs through contact with
infected body fluids (urine, saliva,
blood), as well as sexual contacts.
Cytomegalovirus particles have been
detected in semen for up to 14 months
after exposure,4 and replication in
the testis has been reported in animal
models. 5 Nevertheless, despite a
cytomegalovirus prevalence of 36–90%
depending on age, ethnicity, and
social status, no specific recommen-
dations regarding sexual behaviours
during pregnancy or delay before
conception have ever been elaborated.
The American College of Obstetricians
and Gynecologists, as well as many
other obstetrical agencies, do not
recommend routine cytomegalovirus
www.thelancet.com Vol 389 January 14, 2017
screening for pregnant women or
women attempting to conceive.
The dichotomy between
cytomegalovirus and Zika virus
recommendations calls into question
the rationale for the existing Zika virus
recommendations. Furthermore, the
effectiveness and applicability of such
recommendations are debatable.
Can we really ask all couples living in
and travelling to endemic areas to
have strict protected intercourse for
6 months? What is the efficacy of this
measure considering that in areas with
active Zika virus transmission, couples
are also regularly exposed to mosquito
bites? It is definitely time to get reliable
information on the real burden of
Zika virus vector and non-vector
transmission. This would certainly allow
a de-escalation of the existing empirical
protective measures suggested in
response to the anxiety caused by
the uncertainty around the risks of
materno–fetal Zika virus transmission.
We declare no competing interests.
Manon Vouga, Didier Musso,
Bruno Schaub, Alice Panchaud,
*David Baud
david.baud@chuv.ch
Materno-fetal and Obstetrics Research Unit,
Department “Femme-Mère-Enfant”, University
Hospital, Lausanne 1011, Switzerland (MV, DB);
Institute of Microbiology, Faculty of Biology and
Medicine, University of Lausanne and University
Hospital, Lausanne, Switzerland (MV, DB); Unit of
Emerging Infectious Diseases, Institut Louis
Malardé, Tahiti, French Polynesia (DM);
Multidisciplinary Center of Prenatal Diagnosis,
Obstetrics and Gynecology, Department
“Femme-Mère-Enfant”, University Hospital of
Martinique, Fort de France, France (BS); School of
Pharmaceutical Sciences, University of Geneva and
University of Lausanne, Geneva, Switzerland (AP);
Swiss Teratogen Information Service and Division of
Clinical Pharmacology, University Hospital of
Lausanne, Lausanne, Switzerland (AP); and
Department of Epidemiology, Harvard T H Chan
School of Public Health, Boston, MA, USA (AP)
1 Swaminathan S, Schlaberg R, Lewis J,
Hanson KE, Couturier MR. Fatal Zika virus
infection with secondary nonsexual
transmission. N Engl J Med 2016;
375: 1907–09.
2 Nicastri E, Castilletti C, Liuzzi G, Iannetta M,
Capobianchi MR, Ippolito G. Persistent
detection of Zika virus RNA in semen for
six months after symptom onset in a traveller
returning from Haiti to Italy, February 2016.
Euro Surveill Bull Eur Sur Mal Transm Eur
Commun Dis Bull 2016; 21: 30314.
3 Murray KO, Gorchakov R, Carlson AR, et al.
Prolonged detection of Zika virus in vaginal
secretions and whole blood. Emerg Infect Dis
2017; 23: 99–101.
4 Lang DJ, Kummer JF, Hartley DP.
Cytomegalovirus in semen. Persistence and
demonstration in extracellular fluids.
N Engl J Med 1974; 291: 121–23.
5 Dutko FJ, Oldstone MB. Murine
cytomegalovirus infects spermatogenic cells.
Proc Natl Acad Sci USA 1979; 76: 2988–91.
Zika rash and increased
risk of congenital brain
abnormalities
In a nationwide investigation of
1501 liveborn infants suspected
of congenital Zika virus syndrome
in Brazil, Giovanny V A França and
colleagues (Aug 27, p 891)1 suggest
that microcephaly and rash during
pregnancy are sensitive enough to
screen for cerebral malformations. In
SciencePhoto
their study, the authors report that
the earlier the rash occurred during
pregnancy, the smaller the head
circumference was at birth. Moreover,
“rashes in the third trimester of
pregnancy were associated with brain
abnormalities despite normal sized
heads.” On the basis of the average
value of head circumference for third-
trimester rashes (Z score −1·5 [SD 0·5])
and post-hoc estimation of sensitivity,
specificity, and positive predictive
values obtained from the receiver
operating characteristic curve, we
wish to express our concern that the
data linking third-trimester rashes to
neuroimaging findings are not shown.
According to different scenarios
varying the expected prevalence
rate—which is currently unknown in
Brazil—the projected 87% sensitivity
and 80% specificity observed for the
combination of third-trimester rash
and microcephaly would yield a minimal
prevalence rate of 67·5% to obtain a
positive predictive value of at least
90% (appendix), which represents See Online for appendix
an improbable scenario for a huge
continental country like Brazil, where
space would tend to mitigate the
dynamic of the epidemic. This scenario
151
 Correspondence
would best fit the rapid propagation
encountered in small insular
populations, as observed in school-age
children in French Polynesia.2,3
Nevertheless, we agree with
the authors that congenital brain
abnormalities might be found in
infants with normal sized heads, as
previously reported.4,5
We declare no competing interests.
*Patrick Gérardin,
Van-Mai Cao-Lormeau, Didier Musso,
Philippe Desprès, Marianne Besnard
patrick.gerardin@chu-reunion.fr
INSERM CIC 1410, Centre Hospitalier Universitaire
Réunion, 97448 Saint Pierre Cedex, Réunion, France
(PG); UMR 134 Processus Infectieux en Milieu
Insulaire Tropical, University of La Réunion, CNRS
9192, INSERM 1187, IRD 249, Plateforme
Technologique du CYROI, Sainte Clotilde, Réunion,
France (PG, PD); Institut Louis Malardé, Papeete,
Tahiti, French Polynesia (V-MC-L, DM); and Service
de réanimation néonatale, Centre Hospitalier of
French Polynesia, Pirae, French Polynesia (MB)
1 França GV, Schuler-Faccini L, Oliveira WK, et al.
Congenital Zika virus syndrome in Brazil:
a case series of the first 1501 livebirths with
complete investigation. Lancet 2016;
388: 891–97.
2 Cao-Lormeau VM, Blake A, Mons S, et al.
Guillain-Barré syndrome outbreak associated
with Zika virus infection in French Polynesia:
a case-control study. Lancet 2016; 387: 1531–39.
3 Cauchemez S, Besnard M, Bompard P, et al.
Association between Zika virus and microcephaly
in French Polynesia, 2013–2015: a retrospective
study. Lancet 2016; 387: 2125–32.
4 Brasil P, Pereira JP Jr, Gabaglia R, et al. Zika virus
infection in pregnant women in Rio de Janeiro.
N Engl J Med 2016; 375: 2321–34.
5 Besnard M, Lastère S, Tessier A,
Cao-Lormeau VM, Musso D. Evidence of
perinatal transmission of Zika virus, French
Polynesia, December 2013, and February 2014.
Euro Surveill 2014; 19: 20751.
Authors’ reply
Patrick Gérardin and colleagues state
that “the data linking third-trimester
rashes to neuroimaging findings are
not shown”. In the Results section1
we mention that for nine cases, the
mothers reported a rash in the third
trimester. We have reviewed the
records for these newborn babies: five
presented with typical Zika virus brain
malformations (eg, calcifications,
ventriculomegaly), and physicians
for the remaining four reported
malformations without specifying
152
their precise nature. Three other
Brazilian studies suggest that late
pregnancy infections can lead to brain
lesions: in a prospective cohort,2 five
of the 12 affected fetuses were born
to mothers with a rash on gestational
week 25 or later; a case report3 shows
that a child infected at 26 weeks’
gestation was still shredding the
virus at 2 months of age; and a case-
control study4 reports that three of 32
confirmed cases had a history of rash
in the third trimester. To support their
argument, Gérardin and colleagues
cite a case series5 of 19 fetuses or
newborn babies in Réunion, of whom
five mothers reported a rash in the
first trimester but none in the second
or third trimesters. This small study
does not exclude the possibility that
neuroimaging findings might be
found in the offspring of women with
third-trimester rashes. In our view,
the four Brazilian studies strongly
suggest that Zika virus infections
in late pregnancy can lead to brain
abnormalities.
Gérardin and colleagues’ calculation
of positive predictive value contains
an error. Our receiver operating
characteristic curve refers to definite
and probable cases (including some
that did not present rash), whereas
the average head circumference they
refer to is for third trimester rashes.
They then state that a 67% infection
rate is unlikely in Brazil, but 97% of
our cases are from a smaller region—
the northeast. A case-control study4
has shown 64% antibody prevalence
among controls in Pernambuco state,
where the epidemic was most intense.
In addition, this state saw relatively
few cases of infection in the summer
of 2016 compared with the large
number reported in 2015, suggesting
that herd immunity might have been
achieved—which is compatible with
an incidence of around 60–70% in the
first epidemic wave. In addition, note
that our data show a marked regional
distribution of the epidemic when
it started, and therefore our results
need to be interpreted considering
this spatial distribution rather than
extrapolated to the whole of Brazil.
We declare no competing interests.
*Cesar G Victora, Marcia C Castro,
Giovanny V A França,
Lavinia Schuler-Faccini,
Fernando C Barros
cvictora@equidade.org
Programa de Pós-Graduação em Epidemiologia,
Universidade Federal de Pelotas, Pelotas, Rio Grande
do Sul, Brazil (CGV, FCB); Harvard T H Chan School
of Public Health, Boston, MA, USA (MCC);
Secretariat of Health Surveillance, Ministry of
Health, Brasilia, Brazil (GVAF); Universidade Federal
do Rio Grande do Sul, Rio Grande do Sul, Brazil
(LS-F); and Universidade Católica de Pelotas,
Pelotas, Rio Grande do Sul, Brazil (FCB)
1 França GVA, Schuler-Faccini L, Oliveira WK, et al.
Congenital Zika virus syndrome in Brazil: a case
series of the first 1501 livebirths with complete
investigation. Lancet 2016; 388: 891–97.
2 Brasil P, Pereira JP Jr, Raja Gabaglia C, et al. Zika
virus infection in pregnant women in Rio de
Janeiro. N Engl J Med 2016; 375: 2321–34.
3 Oliveira DBL, Almeida FJ, Durigon EL, et al.
Prolonged shedding of Zika virus associated
with congenital infection. N Engl J Med 2016;
375: 1202–04.
4 de Araujo TV, Rodrigues LC,
de Alencar Ximenes RA, et al. Association
between Zika virus infection and microcephaly
in Brazil, January to May, 2016: preliminary
report of a case-control study. Lancet Infect Dis
2016; 16: 1356–63.
5 Besnard M, Eyrolle-Guignot D,
Guillemette-Artur P, et al. Congenital cerebral
malformations and dysfunction in fetuses and
newborns following the 2013 to 2014 Zika
virus epidemic in French Polynesia.
Euro Surveill 2016; 21: 30181.
The possibility of
vascular care for
prevention of dementia
The study by Eric P Moll van Charante
and colleagues (Aug 20, p 797) 1
showed that vascular care intervention
offered no apparent advantages on the
prevention of dementia, although it
has some useful implications for future
studies.
First, the blood pressure reduction
achieved in the intervention group
indicates that nurse-led vascular care
might be effective in a large population
that is not sufficiently covered by
primary care. In addition, a previous
study2 showed cost effectiveness of
www.thelancet.com Vol 389 January 14, 2017