Accepted Manuscript

Zika virus and the risk of imported infection in returned travelers: implications for
clinical care
Abraham Goorhuis, Karin J. von Eije, Rene A. Douma, Noor Rijnberg, Michele van
Vugt, Cornelis Stijnis, Martin P. Grobusch
PII:

S1477-8939(16)00010-7

DOI:

10.1016/j.tmaid.2016.01.008

Reference:

TMAID 951

To appear in:

Travel Medicine and Infectious Disease

Received Date: 19 January 2016

Accepted Date: 21 January 2016

Please cite this article as: Goorhuis A, von Eije KJ, Douma RA, Rijnberg N, van Vugt M, Stijnis C,
Grobusch MP, Zika virus and the risk of imported infection in returned travelers: implications for clinical
care, Travel Medicine and Infectious Disease (2016), doi: 10.1016/j.tmaid.2016.01.008.
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Zika virus and the risk of imported infection in returned travelers:

implications for clinical care

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Abraham Goorhuis1, Karin J. von Eije2, Rene A. Douma1, Noor Rijnberg1,

Michele van Vugt1, Cornelis Stijnis1, Martin P. Grobusch1

Center of Tropical Medicine and Travel Medicine, Department of Infectious

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Diseases, Division of Internal Medicine, Academic Medical Center, University

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of Amsterdam, Amsterdam, the Netherlands

Laboratory of Clinical Virology, Department of Medical Microbiology, Center

for Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam,

Correspondence to:

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the Netherlands

Abraham Goorhuis, Center of Tropical Medicine and Travel Medicine,

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Department of Infectious Diseases, Division of Internal Medicine, Amsterdam

Medical Center, University of Amsterdam, Meibergdreef 9, PO Box 22660,

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1100 DD Amsterdam, the Netherlands

Phone +31 20 566 4380; fax +31 20 697 2286; email: a.goorhuis@amc.uva.nl

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Since late 2015, an unprecedented outbreak of Zika virus is spreading quickly

across Southern America. After confirmation of the first cases of this flavivirus
infection in May 2015 in Brazil, autochthonous transmission of infections has

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now been reported from Colombia, Suriname, El Salvador, Guatemala,

Martinique, Paraguay, Mexico, Venezuela, the Guyanas, Panama, Honduras,

Puerto Rico, Ecuador, Haiti, Barbados, Bolivia and Saint Martin [1]. The

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number of reported cases is currently in the hundreds of thousands and

undoubtedly reflects only a fraction of the total number of people infected.

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Before the start of the outbreak in The Americas, Zika virus was an
infrequently identified cause of febrile illness, with infections mainly occurring
in isolated localities. After the first description of the virus in a symptomatic
sentinel rhesus monkey in a Yellow Fever study in 1947 (Zika forest, Uganda),

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human infections have been reported from several countries in Sub-Saharan

Africa (1971-2010), South and Southeast Asia (1969-2013), followed by
Micronesia (Yap, 2007), French Polynesia and other Pacific Islands (2013-

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2014), including a large outbreak on Easter Island (2014) [2]. Because the
currently circulating virus strain is most closely related to isolated samples

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from Zika patients in French Polynesia, both belonging to the Asian lineage,
the hypothesis is that the virus was introduced into Brazil through viremic
carriers from this region, possibly during the soccer world cup in 2014 or
during a World Sprint Canoeing championship in Rio de Janeiro in August
2014, in which athletes from four Pacific regions (French Polynesia, New
Caledonia, Cook Islands and Easter Island) competed [3]. However, many

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other routes of introduction are possible.

The large size of the current outbreak in The Americas will also result in an
increase in Zika virus infections among travelers returning from endemic areas.

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To that end, we herewith report five cases of Zika virus infection in returned

travelers to The Netherlands, all of whom acquired the infection in Suriname

(table). All diagnoses were confirmed by PCR (performed at the Erasmus MC,

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Rotterdam, The Netherlands).

All five patients were diagnosed within a time period of 28 days. Common to all

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were a short incubation period (symptoms started on the day of return home in
four patients and four days after return in one patient), extensive
maculopapular skin rash, arthralgias and atypical lymphocytes in the
differential of the white blood cell count (in one patient this was not measured).

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Viral RNA was detected in all patients, as late as the ninth day of illness in two
patients. All five patients recovered quickly without treatment.
Although the clinical syndrome of Zika virus infection is usually mild (the

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disease is sometimes referred to as dengue-light), it is important to establish

the diagnosis for several reasons.

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First, Zika virus is apparently sexually transmissible; one case report describes
a possible sexual transmission of Zika virus by a scientist to his wife
(diagnoses made serologically, not by PCR). He acquired the disease in
Senegal and became symptomatic one week after return to the United States
[4]. Before onset of symptoms, he had sexual intercourse with his wife, who
had never left the United States. She developed similar symptoms a few days

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later. The possibility of sexual transmission was further supported by a second

study that showed high Zika virus RNA loads and replicative virus in semen
and urine of a patient with hematospermia, which had developed 2 weeks after

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clinical cure and clearance of virus from the blood [5]. This observation

suggests that sexual transmission of Zika virus can potentially occur after
recovery from the infection.

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Second, Zika virus infection has been epidemiologically linked to the

occurrence of neurological and auto-immune complications (such as Guillain-

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Barr syndrome) and of congenital microcephaly [1]. Although the perinatal

transmission of Zika virus had already been demonstrated earlier in a study in
French Polynesia, the recent association with congenital microcephaly has
caused much unrest [1,6]. In November 2015, the Brazil International Health

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Regulations National Focal Point reported an approximate 20-fold rise in the

occurrence of congenital microcephaly. This increase occurred mainly in
Northeastern Brazil, where most Zika cases have been reported. French

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Polynesian health authorities also reported an unusual increase in congenital

central nervous system malformations, in a period that coincided with

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outbreaks of Zika virus infection [1]. In addition to these epidemiological

associations, a recent study demonstrated the presence of Zika virus RNA in
amniotic fluid of two mothers who were both pregnant with microcephalic
children [7]. In addition to this published study, the Brazil Ministry of Health
reported the detection of Zika virus genome in blood and tissue samples of
four cases of congenital malformation (two miscarriages and two full-term

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newborns), who died shortly post partum [1]. In January 2016, Zika virus
infection was serologically confirmed in a microcephalic baby born in Hawaii,
from a mother who acquired the infection while living in Brazil [8].

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Because the association has not been observed in earlier Zika virus outbreaks
and because other causes of congenital microcephaly have not been ruled out
in most cases, the European Centre for Disease Prevention and Control

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(ECDC) stated the following: A causative association between microcephaly

in newborns and Zika virus infection during pregnancy is plausible, but not

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enough evidence is available yet to confirm or refute it [9].

In the meantime, with the likely increase in the number of imported cases
among returned travelers, the uncertainty about risk of infection during
pregnancy will undoubtedly lead to concern among pregnant travelers, as we

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are already experiencing in our outpatient clinic of Tropical and Travel

Medicine at the AMC in Amsterdam. In this light, it will be important to be upto-date with the epidemiologic situation and to have adequate diagnostic

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facilities for Zika virus, as PCR is only positive in early infection. Serology may
be a more appropriate tool to rule out recent infection in pregnant women,

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whereas proper perinatal care can be provided in those who test positive for
Zika virus. In addition, physicians should be aware of possible sexual
transmission of the virus, which could lead to locally acquired infections.

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References
1. Pan American Health Organization (PAHO). Zika virus infection.
Available from:

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http://www.paho.org/hq/index.php?option=com_topics&view=article&id=
427&Itemid=41484&lang=en. Accessed at: 19 January 2016.

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2. Tognarelli J, Ulloa S, Villagra E, et al. A report on the outbreak of Zika

[Epub ahead of print]

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virus on Easter Island, South Pacific, 2014. Arch Virol. 2015 Nov 26.

3. Musso D. Zika virus transmission from French Polynesia to Brazil [letter].

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Emerg Infect Dis. 2015. Oct;21(10):1887

4. Foy BD, Kobylinski KC, Foy JLC, et al. Probable NonVector-borne

Transmission of Zika Virus, Colorado, USA. Emerging Infectious

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Diseases. 2011;17(5):880-882. doi:10.3201/eid1705.101939.

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5. Musso D, Roche C, Robin E, et al. Potential Sexual Transmission of

Zika Virus. Emerging Infectious Diseases. 2015;21(2):359-361.
doi:10.3201/eid2102.141363.

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6. Besnard M, Lastre S, Teissier A, Cao-Lormeau VM, Musso D.

Evidence of perinatal transmission of Zika virus, French Polynesia,

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December 2013 and February. Euro Surveill. 2014;19:2075

7. Oliveira Melo AS, Malinger G, Ximenes R, et al. Zika virus intrauterine

infection causes fetal brain abnormaliy and microcephaly: tip of the

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iceberg? Ultrasound Obstet Gynecol. 2016 Jan; 47(1):6-7

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8. http://www.reuters.com/article/us-usa-health-zika-idUSKCN0UU17U.
Accessed at 19 January 2016.

9. European Centre for Disease prevention and Control (ECDC). Rapid

risk assessment: Microcephaly in Brazil potentially linked to the Zika

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virus epidemic 24 November 2015. Stockholm: ECDC; 2015. Available

at: http://ecdc.europa.eu/en/publications/Publications/zika-microcephaly-

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2016.

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Brazil- rapid-risk-assessment-Nov-2015.pdf. Accessed at: 11 January

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Table. Five patients with imported Zika virus infection from Suriname

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Patient 3
Patient 4
54 years
47 years
Male
Male
2 Dec. 2015
4 Dec. 2015
2 Dec. 2015
8 Dec. 2015
10 Dec. 2015
17 Dec. 2015
Yes
Yes
Yes
Yes
Maculopapular:
Maculopapular
Neck, trunk, extremities Whole body excl. face
No
yes
No
No
Yes
Yes
Both ankles
No
No
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
No
Yes
Yes
No
No

Patient 5
53 years
Female
28 Dec. 2015
28 Dec. 2015
30 Dec. 2014
Yes
Yes
Maculopapular
Whole body
No
No
Yes
No
No
Yes
Yes
Yes
Yes
Yes
Not measured
Not measured

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Patient 2
40 years
Female
5 Dec. 2015
5 Dec. 2015
9 Dec. 2015
No
Yes
Maculopapular:
Trunk, extremities
No
Upon thouch
No
No
No
No
Yes
Yes
No
Yes
Yes
No

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Patient 1
60 years
Female
29 Nov. 2015
29 Nov. 2015
2 Dec. 2015
Yes
Yes
Maculopapular:
Rash
Face, trunk, extremities
Itch
Hands
Pain
Upon thouch
Conjunctivitis
Yes
Oedema
Both lower legs
Headache
No
Muscle ache
No
Arthralgias
Yes
Blood abnormalities
Yes
Leucopenia
No
Lymphopenia
No
Yes
Atypical lymphocytes
Elevated liver enzymes
LDH 297 IU/l

Age
Sex
Date of return
Onset of symptoms
PCR diagnosis
Fever
Skin Abnormalities