Confirmed Zika virus infection in a Belgian traveler returning from Guatemala, and the diagnostic challenges of imported cases into Europe

doi:10.1016/j.jcv.2016.04.009

Journal of Clinical Virology

Volume 80, July 2016, Pages 8-11

https://doi.org/10.1016/j.jcv.2016.04.009 Get rights and content

Highlights

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First case of zika virus infection in a Belgian traveler ex Guatemala.
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PCR on serum for rapid diagnosis but restricted to the early phase of infection.
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Interpretation of flavivirus serological tests is challenging.
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Overview of laboratory test results of reported European cases.
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Need for an efficient surveillance for emerging arboviral infections is reminded.

Abstract

We report the first laboratory-confirmed Zika virus (ZIKV) infection in a Belgian traveler after a three week holiday in Guatemala, December 2015. This case along with other imported cases into Europe emphases once again the need for accurate diagnostic tools for this rapidly emerging virus. The challenge is to diagnose patients in the acute phase, which appears short, as serological testing is complicated by cross-reactivity, vaccination status and scarce availability of specific ZIKV tests.

Section snippets

Why this case is important

Zika virus (ZIKV) is a flavivirus transmitted by Aedes mosquitos. Clinical symptoms include fever, rash, arthralgia, myalgia and conjunctivitis, but an estimated 80% of persons infected with ZIKV are asymptomatic [1]. In the acute phase, the clinical presentation is difficult to differentiate from other arbovirus infections such as dengue virus (DENV) and chikungunya virus (CHIKV), which are transmitted by the same vectors and commonly co-circulate in the same geographic area. The course of

Discussion

In the case described here, RT-PCR was positive on serum at day three post symptom onset. In comparison, out of the twelve previously published ZIKV cases imported into Europe [4], [5], [6], [7], [8], [9], [10], [11], [12] (Table 2) an acute phase serum sample (≤5 days), was available in seven cases, of which three cases were positive by ZIKV RT-PCR. Current knowledge on the viral load and variations in ZIKV viremia over time is scarce [2]. The viremic phase appears to be short, as Duffy et al.

Competing interests

The authors declare no competing interests.

Funding

The National Reference Center of arboviruses (ITM) is partially supported by the Belgian Ministry of Social Affairs through a fund within the Health Insurance System. LC holds an innovation mandate from the Flanders Innovation & Entrepreneurship.

Ethical approval

The diagnostic procedures described in this manuscript are part of the standard diagnostic work-up of patients suspected of an arbovirus infection. All samples for routine diagnostic from patients presenting at the Institute of Tropical Medicine (ITM, Antwerp, Belgium) policlinic are stored after completion of the routine tests. The ITM has the policy that sample left-overs of patients presenting at the ITM policlinic can be used for research unless the patients explicitly state their

Acknowledgements

We thank the patient for informed consent for publication. We thank the laboratory staff of ITM for their excellent technical support.

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Time-scaled phylogeography of complete Zika virus genomes using discrete and continuous space diffusion models
2019, Infection, Genetics and Evolution
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ZIKV has now become endemic not only in Souh America and Caribbean, but also in several Pacific islands (American Samoa, the Federated States of Micronesia, Fiji, Marshall Islands, New Caledonia, Samoa and Tonga) (Calvez et al., 2018). In addition, there have been an increasing number of travel-related cases in non-endemic countries such as Australia, Belgium, Canada, China, France, Portugal, Spain, Switzerland and The Netherlands (De Smet et al., 2016). Several authors have attempted to study the dynamics of Zika virus infection through discrete phylogeographical analysis (Boskova et al., 2018; Faria et al., 2017; Giovanetti et al., 2016; Liang et al., 2017; Metsky et al., 2017; Pettersson et al., 2018).
Zika virus (ZIKV), a vector-borne infectious agent that has recently been associated with neurological diseases and congenital microcephaly, was first reported in the Western hemisphere in early 2015.
A number of authors have reconstructed its epidemiological history using advanced phylogenetic approaches, and the majority of Zika phylogeography studies have used discrete diffusion models. Continuous space diffusion models make it possible to infer the possible origin of the virus in real space by reconstructing its ancestral location on the basis of geographical coordinates deduced from the latitude and longitude of the sampling locations. We analysed all the ZIKV complete genome isolates whose sampling times and localities were available in public databases at the time the study began, using a Bayesian approach for discrete and continuous phylogeographic reconstruction.
The discrete phylogeographic analysis suggested that ZIKV emerged to become endemic/epidemic in the first decade of the 1900s in the Ugandan rainforests, and then reached Western Africa and Asia between the 1930s and 1950s. After a long period of about 40 years, it spread to the Pacific islands and reached Brazil from French Polynesia. Continuous phylogeography of the American epidemic showed that the virus entered in north-eastern Brazil in late 2012 and started to spread in early 2013 from two high probability regions: one corresponding to the entire north-east Brazil and the second surrounding the city of Rio de Janeiro, in a mainly northwesterly direction to Central America, the north-western countries of south America and the Caribbean islands. Our data suggest its cryptic circulation in both French Polynesia and Brazil, thus raising questions about the mechanisms underlying its undetected persistence in the absence of a known animal reservoir, and underline the importance of continuous diffusion models in making more reliable phylogeographic reconstructions of emerging viruses.
Evolution of symptoms and quality of life during Zika virus infection: A 1-year prospective cohort study
2018, Journal of Clinical Virology
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Diagnosis is critical for the general practitioner to monitor patients for the right infection, as dengue can lead to more severe complications than ZIKV disease, and ZIKV infection can lead to Zika congenital syndrome. From a public health point of view, an efficient case definition permits better reactivity when ZIKV emerges in a new territory [10,14,29]. Many epidemiological definitions have been published by international organizations and national governments [30].
Although the complications of Zika virus infection have been well described, the clinical pattern has not been reported in enough detail to differentiate this infection from those with other arboviroses, and no longitudinal study has yet been published on the persistence of symptoms and quality of life.
were to describe bio-clinical pattern and quality of life during ZIKV infection, and their evolution.
We present a 1-year clinical follow-up of 49 people infected with Zika virus in French Guiana, for whom the diagnosis was confirmed by RT-PCR in serum or urine.
Fever was inconsistent (95% confidence interval (CI), 39–67). Exanthema (CI, 84–100) was maculopapular, with pruritus and conjunctivitis, variable over time and disappeared 12 days after the onset of symptoms (CI, 10–14). Joint pain (CI, 39–67) occurred mainly in the hands, wrists, knees and ankles and lasted for 10 days (CI, 7–13). Asthenia (CI, 61–85) scored low (3/10) but lasted for 19 days (CI, 16–22). The last two symptoms strongly limited patients’ activities in the acute stage of the disease (RAPID-3 score, CI, 5–8). None of the patients had neurological complications, but 41% (CI, 27–55) had areflexia during the first month.
We found no real chronic evolution or decreased quality of life, function or ability to work from the first month after symptom onset.
Can Zika virus antibodies cross-protect against dengue virus?
2018, The Lancet Global Health
Zika virus: History, epidemiology, transmission, and clinical presentation
2017, Journal of Neuroimmunology
Citation Excerpt :
As illustrated in Fig. 2, ZIKV is a potential pandemic threat, currently circulating not only in the Americas but also in the Pacific Islands (American Samoa, Federated States of Micronesia, Fiji, Marshall Islands, New Caledonia, Palau, Papua New Guinea, Samoa, and Tonga), Southeast Asia (Singapore, Thailand, the Philippines, and Vietnam), and the islands of Cape Verde off the coast of West Africa (CDC, 2016a; ECDC, 2016a; WHO, 2016b). In addition, since early 2015, there have been an increasing number of travel-related imported ZIKV cases in non-endemic countries: Australia (AGDH, 2016; Pyke et al., 2016), Belgium (De Smet et al., 2016), Canada (GC, 2016), China (Yin et al., 2016; Zhang et al., 2016b), France (Maria et al., 2016), the US (Hawaii) (CDC, 2016b), Italy (Nicastri et al., 2016b), Portugal (Ze-Ze et al., 2016), Spain (Diaz-Menendez et al., 2016), Switzerland (Gyurech et al., 2016), and the Netherlands (Duijster et al., 2016). Using species distribution modeling techniques, a recent study has predicted that a large portion of the tropical and sub-tropical regions of the globe has suitable environmental conditions but has not yet reported symptomatic cases of ZIKV infection (Fig. 3), with over two billion people living in these areas (Messina et al., 2016).
Zika virus (ZIKV), a mosquito-borne positive-stranded RNA virus of the family Flaviviridae (genus Flavivirus), is now causing an unprecedented large-scale outbreak in the Americas. Historically, ZIKV spread eastward from equatorial Africa and Asia to the Pacific Islands during the late 2000s to early 2010s, invaded the Caribbean and Central and South America in 2015, and reached North America in 2016. Although ZIKV infection generally causes no symptoms or only a mild self-limiting illness, it has recently been linked to a rising number of severe neurological diseases, including microcephaly and Guillain-Barré syndrome. Because of the continuous geographic expansion of both the virus and its mosquito vectors, ZIKV poses a serious threat to public health around the globe. However, there are no vaccines or antiviral therapies available against this pathogen. This review summarizes a fast-growing body of literature on the history, epidemiology, transmission, and clinical presentation of ZIKV and highlights the urgent need for the development of efficient control strategies for this emerging pathogen.
Zika Virus
2017, Clinics in Laboratory Medicine
Citation Excerpt :
However, it should be noted that specimens in this study were collected within 10 days after onset of symptoms, well after the currently recommended window of 7 days. In a study of Zika cases imported into Europe, 3 (43%) of 7 acute phase specimens (within 5 days of illness onset) were positive by RT-PCR.50 Finally, acute phase sera tested from 262 clinically suspected Zika cases in Brazil were tested by RT-PCR, and 119 (45.4%) were positive.35
A cross-sectional analysis of Zika virus infection in symptomatic and asymptomatic non-pregnant travellers: Experience of a European reference center during the outbreak in the Americas
2019, Travel Medicine and Infectious Disease
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Eight cases (3.7%) had travelled to SAM, 23 (20.4%) to CAM and 22 (15.0%) to CAR. The median duration of travel was longer for ZIKV-cases (29 days, IQR [18–264] vs. 19 days IQR [12–32], p = 0.06), but the difference was not significant, particularly after exclusion of the ‘resident’ travel type (Table 2). The first day of illness was recorded for 188 of symptomatic travellers, including 43 ZIKV cases.
Zika virus (ZIKV) infection a concern to travellers because of potential sexual transmission and adverse pregnancy outcomes.
To describe our experience in diagnosing ZIKV in travellers returning from endemic territories.
Travellers were evaluated for ZIKV at our clinic in a 12-month period during the outbreak, using ZIKV-specific RT-PCR and anti-ZIKV Immunoglobulin M/G ELISA when symptomatic, and ELISA only for asymptomatic travellers, preferably from 20 days after the last exposure. All positive ELISA results were subject to confirmation by Virus Neutralization Testing. We estimated post-test probabilities of ZIKV in asymptomatic travellers.
Of 462 travellers, 227 reported symptoms and 235 did not. Asymptomatic travellers had similar baseline characteristics, but were younger (median age 31 vs. 33 years, p = 0.01) and had reproductive concerns more often (75.8% vs. 24.2%). ZIKV infection was confirmed in 49 cases: 46/227 (20.3%) were symptomatic and 3/235 (1.3%) asymptomatic. Rash (positive likelihood ratio (LRP) 5.6) and conjunctivitis (LRP 10.8) predicted ZIKV infection. The post-test probability of a negative ELISA-result at 20–25 days was below 0.1%.
ZIKV infection was frequent in symptomatic, but not in asymptomatic travellers. We consider negative ELISA results at 20–25 days after exposure a safe strategy to rule out ZIKV infection. Testing for ZIKV-specific antibodies within this timeframe could be particularly valuable in the management of returning travellers who wish to conceive.

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Case reportConfirmed Zika virus infection in a Belgian traveler returning from Guatemala, and the diagnostic challenges of imported cases into Europe

Highlights

Abstract

Section snippets

Why this case is important

Discussion

Competing interests

Funding

Ethical approval

Acknowledgements

J. Clin. Virol.

Lancet

Zika virus outbreak on yap island, federated states of Micronesia

N. Engl. J. Med.

State of knowledge on Zika virus for an adequate laboratory response

Bull. World Health Organ.

Update: interim guidelines for health care providers caring for pregnant women and women of reproductive age with possible Zika virus exposure—United States, 2016

MMWR Morb. Mortal. Wkly. Rep.

Zika without symptoms in returing travellers, what are the implications

Travel Med. Infect. Dis.

False positive dengue NS1 antigen test in a traveller with an acute Zika virus infection imported into Switzerland

Swiss Med. Wkly.

Zika virus infection in a traveller returning from the Maldives

Euro Surveill.

Zika virus infections in three travellers returning from South America and the Caribbean respectively, to Montpellier, France, December 2015 to January 2016

Euro Surveill.

First case of laboratory-confirmed Zika virus infection imported into Europe November 2013

Euro Surveill.

Case report
Confirmed Zika virus infection in a Belgian traveler returning from Guatemala, and the diagnostic challenges of imported cases into Europe