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Chikungunya and Zika Virus

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Europe’s journal on infectious disease epidemiolog y, prevention and control

Special edition:

Chikungunya and Zika virus
October 2014

Featuring
• Spread of chikungunya from the Caribbean to mainland Central and South America: a greater risk of spillover in Europe?
• Aspects of Zika virus transmission
• Cases of chikungunya virus infection in travellers returning to
Spain from Haiti or Dominican Republic, April-June 2014

www.eurosurveillance.org

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Contents
Chikungunya and Zika

Zika

Editorial

Rapid communications

Integrated surveillance for prevention and control of emerging vector-borne diseases in Europe

50
54

Zika virus infection complicated by Guillain-Barré syndrome – case report, French Polynesia,
December 2013

Chikungunya

Two cases of Zika fever imported from French
Polynesia to Japan, December 2013 to January 2014
First case of laboratory-confirmed Zika virus infection imported into Europe, November 2013

JC Semenza et al.

2

58

Evidence of perinatal transmission of Zika virus,
French Polynesia, December 2013 and February 2014

61

Potential for Zika virus transmission through blood transfusion demonstrated during an outbreak in
French Polynesia, November 2013 to February 2014

65

S Kutsuna et al.

D Tappe et al.

Editorials
Spread of chikungunya from the Caribbean to mainland Central and South America: a greater risk of spillover in Europe?
H Noël et al.

6

Rapid communications
Dengue virus serotype 4 and chikungunya virus coinfection in a traveller returning from Luanda,
Angola, January 2014
R Parreira et al.

E Oehler et al.

M Besnard et al.

9

D Musso et al.

Emergence of chikungunya fever on the French side of Saint Martin island, October to December 2013

13

Importance of case definition to monitor ongoing outbreak of chikungunya virus on a background of actively circulating dengue virus, St Martin,
December 2013 to January 2014

17

Cases of chikungunya virus infection in travellers returning to Spain from Haiti or Dominican
Republic, April-June 2014

20

Large number of imported chikungunya cases in mainland France, 2014: a challenge for surveillance and response

25

S Cassadou et al.

R Omarjee et al.

A Requena-Méndez et al.

MC Paty et al.

Euroroundups
Chikungunya outbreak in the Caribbean region,
December 2013 to March 2014, and the significance for Europe

30

W Van Bortel et al.

Research article
Local and regional spread of chikungunya fever in the Americas
S Cauchemez et al.

41

© Eurosurveillance
Illustration of mosquito, map of outbreak

www.eurosurveillance.org

1

Editorials

Integrated surveillance for prevention and control of emerging vector-borne diseases in Europe
J C Semenza (Jan.semenza@ecdc.europa.eu)1, H Zeller1
1. European Centre for Disease Prevention and Control, Stockholm, Sweden
Citation style for this article:
Semenza JC, Zeller H. Integrated surveillance for prevention and control of emerging vector-borne diseases in Europe. Euro Surveill. 2014;19(13):pii=20757.
Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20757
Article submitted on 28 March 2014 / published on 3 April 2014

World Health Day, celebrated on 7 April, marks the anniversary of the founding of the World Health
Organization (WHO) in 1948. This year, vector-borne diseases which are transmitted mainly by bites of vectors such as mosquitoes, ticks and sandflies are highlighted as a global public health priority. This issue of Eurosurveillance focuses on vector-borne diseases and their impact on public health in Europe and other parts of the world such as the recent outbreaks of Chikungunya fever in the Caribbean and Zika virus fever in the Pacific [1-6].

Mosquito-borne diseases

Dengue and malaria are important mosquito-borne viral diseases, often also referred to as ‘tropical’ diseases. Globally, dengue is the most common mosquitoborne viral disease, with an estimated 390 million infections per year and 40% of the world’s population at risk [7]. While interventions to control mosquitoes have resulted in a decrease of malaria cases, WHO nonetheless estimates that 219 million individuals were infected in 2010, of which 660,000 died, predominantly in Africa [8].
Yet, vector-borne diseases are also a threat to public health in Europe. Mounting an effective public health response can counteract challenges posed by them and protect humans from infections; dedicated activities such as disease and vector surveillance as well as monitoring infectious disease drivers (e.g. environmental or climatic conditions) can help to anticipate and to respond to emerging vector-borne diseases [9, 10].
Globalisation and environmental change; social and demographic change; and health system capacity are three interacting drivers that can set the stage for novel vector-borne disease scenarios [11]. The changing dynamic of these drivers can potentially create new constellations of threats that challenge control measures. Pathogens and vectors are bound to disseminate rapidly through globalised transportation networks: over 100 million air travellers alone enter continental
Europe annually, connecting it to international ‘hot
2

spots’ of emerging infectious diseases [12]. A casein-point is the importation, establishment and expansion of the Asian tiger mosquito (Aedes albopictus), first recorded in Albania in the 1970s and subsequently in Italy in the 1990s. The mosquito was imported in used car tires from the United States into Genova and
Venice, both in Italy, from where the mosquito spread
[13]. Dedicated vector surveillance activities (Figure 1) have documented that the vector has expanded due to permissive climatic and environmental conditions and is now established in numerous regions in Europe.
Astute surveillance activities were able to detect the autochthonous transmission of Chikungunya and dengue viruses by Ae. albopictus in Europe triggered by infected travellers returning from endemic areas [13,
14]. Through vector surveillance, Ae. aegypti mosquitoes, the main vectors of dengue, were first detected in Madeira, Portugal in 2005 where they dispersed across the southern coastal areas of the island. From
September 2012 to January 2013, the island experienced a large dengue outbreak, affecting more than
2,100 individuals, including 78 cases exported to continental Europe; the responsible dengue virus serotype
DEN-1 was traced back to a probable Central or South
American origin [15].
In December 2013, public health surveillance confirmed the first local transmission of Chikungunya virus in the
Caribbean. Within three months the virus spread from
Saint Martin island to six other neighbouring islands and autochthonous transmission was even reported in French Guiana, South America. Cassadou et al. and
Omarjee et al. in this issue describe the importance of proactive public health practice during such a vectorborne disease emergence [1]. Chikungunya infections were identified in a cluster of patients suffering from a febrile dengue-like illness with severe joint pain and who tested negative for dengue. The outbreak illustrates the importance of a preparedness plan with awareness of healthcare providers, adequate laboratory support for early pathogen identification, and www.eurosurveillance.org Figure
Currently known vector surveillance activities in Europe, January 2014

The surveillance activities include not only specific surveillance studies but also work done as part of on-going control activities, research projects and inventory studies.
Source: European Center for Disease Prevention and Control, 2014 [25].

appropriate response. Incidentally, in the past, several imported cases of Chikungunya fever were reported but did not result in local transmission or spread to surrounding islands.
Zika virus, transmitted by Ae. aegypti mosquitoes and originated from Africa and Asia emerged in French
Polynesia in September 2013 and posed another health threat by Ae. albopictus mosquitos [16]. In this issue,
Musso et al. report the first evidence of perinatal transmission of the Zika virus [2].
The parasitic mosquito-borne disease malaria was once common mainly in southern parts of Europe.
While it had been eliminated largely via sanitary measures, local transmission has sporadically returned to Europe in recent years and cases from endemic www.eurosurveillance.org countries continue to be routinely imported into Europe via travelers. In Greece, malaria had been eliminated in 1974 but starting in summer 2009 through 2012, locally acquired cases of Plasmodium vivax occurred in the summer months, mostly due to multiple re-introductions of the parasite [14]. The continuous spread of
P. vivax by local anopheline mosquitoes raised the possibility of a sustained malaria transmission. In order to guide malaria control, areas with suitable environments for persistent transmission cycles were identified through multivariate modelling of environmental variables [17]. With information about this environmental fingerprint and using European Union (EU) structural funds, adequate measures could be taken and transmission in these areas was interrupted. Targeted epidemiological and entomological surveillance, vector abatement activities, and awareness raising among the
3

general public and health workers proved to be successful to this effect.
A further important viral vector-borne disease is West
Nile fever (WNF). It was first recognised in Europe in the 1950s and re-emerged in Bucharest in 1996 and
Volgograd in 1999 [13, 14]. Since then, several countries experienced limited outbreaks until 2010, when
Europe witnessed an unprecedented upsurge in the numbers of WNF cases [18]. Ambient temperature deviations from a thirty year average during the summer months correlated with a WNF outbreak of over 1,000 cases in newly affected areas of south-eastern Europe
[19]. Since the emergence of WNF in Greece in 2010, the disease has spread in the country reaching both rural and urban areas. In the subsequent summers from
2011 to 2013, the outbreaks did not subside in these areas. An article by Pervanidou et al. in the current issue describes the third consecutive year of autochthonous West Nile virus transmission in Greece [3]. It is a descriptive analysis of the 2012 outbreak, confirming risk factors such as advanced age, for severity of disease and medical risk factors such as chronic renal disease, for mortality from WNF.
Temperature determines viral replication rates, growth rates of vector populations and the timing between blood meals, thereby accelerating disease transmission [18]. With global climate change on the horizon, rising temperatures might be a climatic determinant of future WNV transmission that can be used as an early warning signal for vector abatement and public health interventions [13].

Tick-borne diseases

Tick-borne diseases are also of public health concern in Europe. Tick-borne encephalitis (TBE) is endemic in
Europe and due to its medical significance was recently added to the list of notifiable diseases with a harmonised case definition focussing on neuroinvasive illness with laboratory confirmation [20]. The main vector of TBE, Ixodes ricinus, is widely distributed in Europe while TBE virus transmission is restricted to specific foci. Integrated surveillance is important to precisely determine these locations of active transmission to humans to better assess the risk and inform the public about adequate preventive measures which include protective clothing as well as vaccination. Schuler et al. in this issue describe the epidemiological situation of TBE in Switzerland over a five year period, showing the heterogeneity of the incidence according to cantons and the importance of the surveillance and vaccination as a preventive measure [4].
Tick activity is determined by ecological environmental conditions [21]. TBE incidence has been affected by both climatic and socio-demographic factors [13].
The political changes in the 1990s after the dissolution of the former Soviet Union, might have contributed to the transmission of TBEV in the Baltic countries
(Estonia, Latvia and Lithuania) and in eastern Europe
4

by increasing the vulnerabilities for some population subgroups. A case control study from Poland found that spending extended periods of time in forests harvesting forest foods such as mushrooms, being unemployed or employed as a forester significantly increased the risk for TBE infections [22]. In central
Europe, climate change-related temperature rise has been linked to an expansion of TBE virus transmitting ticks into higher altitude [23].
Lyme borreliosis, another endemic tick-borne disease, is believed to be the vector-borne disease with the highest burden in Europe. Climate change may be affecting the risk of Lyme borreliosis in Europe [13]; it has already been demonstrated that Borrelia transmitting ticks have been associated with an expansion into higher latitudes in Sweden [24].
Collectively, these examples demonstrate that vectorborne diseases remain an important challenge to public health in Europe. Monitoring environmental and climatic precursors of vector-borne diseases linked to integrated surveillance of human cases and vectors can help counteract potential impacts [9, 10]. Certainly, raising awareness and increasing knowledge among the general public, public health practitioners, and policy makers about disease vectors and their relationship with infectious diseases remains a priority also.
Exposure prevention through personal protection and vector abatement are important components of effective intervention strategies. In addition, integrated vector surveillance of invasive and endemic mosquito species is crucial for effective prevention and control of vector-borne diseases.
References
1. Cassadou S, Boucau S, Petit-Sinturel M, Huc P, Leparc-Goffart
I, Ledrans M. Emergence of chikungunya fever on the French side of Saint Martin island, October to December 2013. Euro
Surveill. 2014;19(13):pii=20752.
2. Besnard M, Lastère S, Teissier A, Cao-Lormeau VM, Musso
D. Evidence of perinatal transmission of Zika virus, French
Polynesia, December 2013 and February 2014 . Euro Surveill.
2014;19(13):pii=20751.
3. Pervanidou D, Detsis M, Danis K, Mellou K, Papanikolaou
E, Terzaki I, Baka A, Veneti L, Vakali A, Dougas G, Politis C,
Stamoulis K, Tsiodras S, Georgakopoulou T, Papa A, Tsakris A,
Kremastinou J, Hadjichristodoulou C. West Nile virus outbreak in humans, Greece, 2012: third consecutive year of local transmission. Euro Surveill. 2014;19(13):pii=20758.
4. Schuler M, Zimmermann H, Altpeter E, Heininger U.
Epidemiology of tick-borne encephalitis in Switzerland, 2005 to 2011. Euro Surveill. 2014;19(13):pii=20756.
5. Van Bortel W, Dorleans F, Rosine J, Blateau A, Rousseau D,
Matheus S, Leparc-Goffart I, Flusin O, Prat CM, Césaire R,
Najioullah F, Ardillon V, Balleydier E, Carvalho L, Lemaître
A, Noël H, Servas V, Six C, Zurbaran M, Léon L, Guinard A, van den Kerkhof J, Henry M, Fanoy E, Braks M, Reimerink J,
Swaan C, Georges R, Brooks L, Freedman J, Sudre B, Zeller H.
Chikungunya outbreak in the Caribbean region, December 2013 to March 2014, and the significance for the European Union.
Euro Surveill. 2014;19(13):pii=20759.
6. Omarjee R, Prat CM, Flusin O, Boucau S, Tenebray B, Merle
O, et al. Importance of case definition to monitor ongoing outbreak of chikungunya virus on a background of actively circulating dengue virus, St Martin, December 2013 to January
2014. Euro Surveill. 2014;19(13):pii=20753.
7. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes
CL, et al. The global distribution and burden of dengue. Nature
2013; 496(7446): 504-7. http://dx.doi.org/10.1038/nature12060

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8. World Health Organization (WHO). Factsheet on the
World Malaria Report 2012. [Accessed 28 Mar 2014].
Available from: http://www.who.int/malaria/media/ world_malaria_report_2012_facts/en/. 9. Semenza JC, Sudre B, Oni T, Suk JE, Giesecke J. Linking environmental drivers to infectious diseases: the European environment and epidemiology network. PLoS Negl Trop
Dis 2013; 7(7): e2323. http://dx.doi.org/10.1371/journal. pntd.0002323 10. Nichols GL, Andersson Y, Lindgren E, Devaux I, Semenza
JC. European Monitoring Systems and Data for Assessing
Environmental and Climate Impacts on Human Infectious
Diseases. Int J Environ Res Public Health 2014; 11
(forthcoming).
11. Suk JE, Semenza JC. Future infectious disease threats to
Europe. Am J Public Health. 2011; 101(11): 2068-79. http:// dx.doi.org/10.2105/AJPH.2011.300181 12. Jones KE, Patel NG, Levy MA, Storeygard A, Balk D, Gittleman
JL, et al. Global trends in emerging infectious diseases.
Nature. 2008; 451(7181): 990-3. http://dx.doi.org/10.1038/ nature06536 13. Semenza JC, Menne B. Climate change and infectious diseases in Europe. Lancet Infect Dis 2009; 9(6): 365-75. http://dx.doi. org/10.1016/S1473-3099(09)70104-5 14. Zeller H, Marrama L, Sudre B, Van Bortel W, Warns-Petit E.
Mosquito-borne disease surveillance by the European Centre for Disease Prevention and Control. Clin Microbiol Infect. 2013;
19(8): 693-8. http://dx.doi.org/10.1111/1469-0691.12230
15. Alves MJ, Fernandes PL, Amaro F, Osorio H, Luz T, Parreira
P, et al. Clinical presentation and laboratory findings for the first autochthonous cases of dengue fever in Madeira island,
Portugal, October 2012. Euro Surveill. 2013;18(6):pii=20398.
16. Wong PS, Li MZ, Chong CS, Ng LC, Tan CH. Aedes (Stegomyia) albopictus (Skuse): a potential vector of Zika virus in
Singapore. PLoS Negl Trop Dis. 2013; 7(8): e2348. http:// dx.doi.org/10.1371/journal.pntd.0002348 17. Sudre B, Rossi M, Van Bortel W, Danis K, Baka A, Vakalis N, et al. Mapping environmental suitability for malaria transmission,
Greece. Emerg Infect Dis. 2013; 19(5): 784-6. http://dx.doi. org/10.3201/eid1905.120811 18. Paz S, Semenza JC. Environmental drivers of West Nile fever epidemiology in Europe and Western Asia--a review. Int J
Environ Res Public Health. 2013; 10(8): 3543-62. http://dx.doi. org/10.3390/ijerph10083543 19. Paz S, Malkinson D, Green MS, Tsioni G, Papa A, Danis K, et al. Permissive summer temperatures of the 2010 European
West Nile fever upsurge. PLoS One. 2013; 8(2): e56398. http:// dx.doi.org/10.1371/journal.pone.0056398 20. Amato-Gauci AJ, Zeller H. Tick-borne encephalitis joins the diseases under surveillance in the European Union. Euro
Surveill. 2012;17(42):pii=20299.
21. Medlock JM, Hansford KM, Bormane A, Derdakova M,
Estrada-Pena A, George JC, et al. Driving forces for changes in geographical distribution of Ixodes ricinus ticks in Europe. Parasit Vectors. 2013; 6: 1. http://dx.doi. org/10.1186/1756-3305-6-1 22. Stefanoff P, Rosinska M, Samuels S, White DJ, Morse DL,
Randolph SE. A national case-control study identifies human socio-economic status and activities as risk factors for tickborne encephalitis in Poland. PLoS One. 2012; 7(9): e45511. http://dx.doi.org/10.1371/journal.pone.0045511 23. Daniel M, Materna J, Honig V, Metelka L, Danielova V, Harcarik
J, et al. Vertical distribution of the tick Ixodes ricinus and tick-borne pathogens in the northern Moravian mountains correlated with climate warming (Jeseniky Mts., Czech
Republic). Cent Eur J Public Health. 2009; 17(3): 139-45.
24. Lindgren E, Talleklint L, Polfeldt T. Impact of climatic change on the northern latitude limit and population density of the disease-transmitting European tick Ixodes ricinus.
Environ Health Perspect. 2000; 108(2): 119-23. http://dx.doi. org/10.1289/ehp.00108119 25. European Centre for Disease Prevention and Control (ECDC).
Available from: http://www.ecdc.europa.eu/en/healthtopics/ vectors/vector-maps/Pages/VBORNET_maps.aspx www.eurosurveillance.org

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Editorials

Spread of chikungunya from the Caribbean to mainland
Central and South America: a greater risk of spillover in
Europe?
H Noël (h.noel@invs.sante.fr)1, C Rizzo2
1. French Institute for Public Health Surveillance (Institut de Veille Sanitaire; InVS), Saint-Maurice, France
2. National Centre for Epidemiology, Surveillance and Health Promotion, National Institute of Health (Istituto Superiore di Sanità;
ISS), Rome, Italy
Citation style for this article:
Noël H, Rizzo C. Spread of chikungunya from the Caribbean to mainland Central and South America: a greater risk of spillover in Europe? . Euro Surveill.
2014;19(28):pii=20855. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20855
Article submitted on 15 July 2014 / published on 17 July 2014

After a decade of outbreaks in Africa, the Indian Ocean and Asia, chikungunya virus (CHIKV) is stepping out of the shadow of dengue virus [1]. Although these two mosquito-borne viruses share clinical characteristics and their main vectors, Aedes albopictus (the tiger mosquito) and Ae. aegypti, CHIKV has long remained exotic to the western hemisphere [2]. The emergence of the Indian Ocean lineage changed the views on CHIKV when it caused an unprecedented disease burden in
India and the islands of the Indian Ocean between
2005 and 2008 [3,4].
More than the reports of single events of locallyacquired cases of chikungunya fever in Italy and France
[5,6], the recent occurrence of autochthonous transmission of CHIKV in the Americas has redesigned the geographic distribution of the virus. An outbreak in the Caribbean caused by an Asian strain of the virus started in Saint Martin in October 2013 with Ae. aegypti as the primary vector. The dynamics of the spread of
CHIKV was in line with that in outbreaks that occurred in the Indian Ocean [2].
In this issue of Eurosurveillance, Cauchemez et al. estimate the basic reproductive number (the mean number of new host cases generated by one infectious host in a completely susceptible human population) at between
2 and 4 in the initial phase of the outbreak in the French
Caribbean [7]. This is close to estimates from the outbreaks in Italy in 2007 and on Réunion Island in 2006
(3.5 and 3.7, respectively) [8,9].
Data from epidemiological surveillance suggest that so far, six months after its introduction to the Caribbean,
CHIKV has been responsible for over 350,000 suspected cases of chikungunya fever that have occurred throughout the region [10].
The consequences of the outbreaks in the
Caribbean have ripples in Europe, as Paty et al. and
6

Requena-Méndez et al. document in this issue [11,12].
Paty et al. report the increased detection through surveillance of infected travellers arriving in mainland
France from the French West Indies [11]. Likewise, the importation of chikungunya cases presented by
Requena-Méndez et al. in this issue are likely to continue for months in Spain and other countries with intense exchanges with South America [12]. Cauchemez et al. stress that if circulation of CHIKV settles in mainland South and Central America, the international spillover of cases could escalate [7]. At this moment, public health surveillance has already detected local transmission of CHIKV on the continent, in Costa Rica,
Guyana, El Salvador, Suriname and French Guiana [10].
Based on the recent rapid risk assessment from the
European Centre for Disease Prevention and Control
(ECDC), the chikungunya epidemic in the Americas represents a tangible threat to public health in Europe that goes beyond the scope of travellers’ health [13].
In this globalised world, it could ignite local diffusion of CHIKV in Madeira that is colonised by Ae. aegypti and in the constantly expanding areas in Europe where
Ae. albopictus is established. Vector competence studies are ongoing, but it is highly likely that Ae. albopictus will be found competent for transmission of the
CHIKV strain circulating in the Caribbean. Local tiger mosquitoes were able to transmit CHIKV strains of the
Indian Ocean lineage to more than 250 cases in Italy in
2007 and to two cases in France in 2010 [5,6].
Local foci or even large outbreaks are more likely to occur in Europe now because of the synchronicity between CHIKV transmission on the other side of the
Atlantic and the season of vector activity in Europe.
Preventing the spillover of the chikungunya outbreak to
Europe in this challenging context requires the mobilisation of the population and cross-sector collaboration between clinicians, medical biologists, entomologists

www.eurosurveillance.org

and public health professionals at local, national and
European level in as part of the One Health concept.

areas, without waiting for laboratory confirmation results. The odds of controlling CHIKV dissemination to Europe will become lower if, as expected, CHIKV spreads during the summer to continental South America. Indeed, it is plausible that the long feared epidemic in South
America will be ongoing for months and maybe years, continuously fuelling the flow of imported cases.

However, underreporting of cases can be substantial.
Published reports suggest that the estimated number of imported cases generally exceeds the number of notified cases by a factor 10 and over [15,16]. Active mobilisation of clinicians and medical biologists in targeted geographical areas has proven efficient to improve completeness of the surveillance of dengue virus and captured up to 69% of cases [16].

There are no prospects of a human vaccine or curative antiviral treatment available in a near future.
Therefore, the only opportunity of preventing dissemination to Europe consists in reducing the vector density and its contacts with humans. People living in an area colonised by Aedes vector mosquitoes should be taught how to prevent and eliminate man-made breeding sites to reduce the overall vector density around their homes and workplaces. They should be informed about personal protective measures to avoid mosquito bites such as wearing long-sleeve shirts and long trousers and using repellent on exposed skin. Travellers should strictly observe the recommendations for personal protection against mosquito bites while visiting areas where CHIKV transmission is active. In case of fever upon return to an area where the vector is established, travellers should seek medical attention and prevent mosquito bites while symptomatic. Because both vector mosquitoes are day biters, nets are of limited use. But they can be useful to protect in particular young children and infected patients that are resting.
Healthcare professionals should become increasingly aware of the clinical presentation and diagnostics of chikungunya, as well as treatment relieving symptoms.
They should advise travellers and cases about protective measures against mosquitoes.
Vector control measures should target both adult mosquitoes and larvae and rely on a limited set of insecticides that are active against Aedes spp. These insecticides should be used sparingly and only for targeted responses so as to avoid toxic effects on humans and the surrounding fauna as well as the emergence of resistant insects. For this reason, implementing surveillance systems for local entomological indicators in
Europe is crucial in order to estimate the risk of local transmission associated with imported cases and to guide vector control measures in time and space.
Thus, it is crucial to be prepared. European Union (EU)
Member States are advised to develop preparedness planning for identifying new health threats at national level according to the recent Decision 1082/2013/EU on serious cross-border threats to health [14]. The CHIKV control measures at EU level require: entomological surveillance, surveillance of imported and autochthonous cases and rapid diagnosis to detect local outbreaks. Moreover, vector control measures should be included in the planning around cases, either after rapid diagnosis or, in patients returning from epidemic

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At this stage, surveillance should be based primarily on laboratory confirmation. At EU level, new case definitions for dengue and chikungunya fever are being developed, based on the group discussion that took place during the meeting of ECDC Emerging and Vectorborne Diseases (EVD) network in December 2013 [17].
A case definition including only epidemiological and clinical criteria should be considered to monitor large outbreaks when systematic laboratory confirmation is not feasible any more.
The threat that the chikungunya outbreak in the western hemisphere represents for public health in Europe, should not overshadow the risk posed by other arboviruses such as dengue virus. Globalisation and environmental changes affect the dynamics of both viruses in Europe in the same way. Recent reports of limited autochthonous transmission of dengue virus and large-scale outbreaks in Europe call for continued vigilance and involvement [18-20]. When confronted with a febrile patient returning from tropical and subtropical areas, practitioners should now consider both diagnoses. Both mosquito-borne viral diseases can be tackled by the same surveillance and response efforts.
Laboratory capacity for CHIKV infections in the EU is limited and should be increased for early detection of cases. In 2007, the European Network for Diagnostics of ‘Imported’ Viral Diseases (ENIVD) conducted an external quality assurance survey of serological and molecular methods used for CHIKV detection [21]. That study unveiled great differences in the availability and performance of CHIKV diagnostics among the 24 participating laboratories from 15 countries across Europe.
There is little available information to make us believe that the situation since has notably improved. Most of these laboratories are still using in-house techniques and may not be able to cope with a considerable increase in activity. New and reliable commercial serological and molecular tests are needed to improve access to CHIKV diagnostics in Europe.
CHIKV also represents a threat for blood safety in
Europe. The recent detection of CHIKV among blood donors from Guadeloupe and Martinique in early 2014 alerts us to the risk of transfusion-transmitted infections [22]. Temporary deferral of donors returning from areas of active transmission of CHIKV is an effective way of preventing transfusion-transmitted infections.
7

In case of local transmission of CHIKV in the EU, different measures should be considered according to the intensity of vector-borne transmission in the community. These measures include discontinuing blood collection in affected areas, screening donors for symptoms, post-donation quarantine and CHIKV RNA detection in donations.
In summary, the introduction of chikungunya in the
Caribbean and the Americas illustrates how quickly diseases can spread with international travel. In the coming months, chikungunya cases among travellers visiting or returning to Europe are likely to increase.
European public health authorities should therefore not underestimate the transmission potential of CHIKV and should remain vigilant. These imported cases could trigger local outbreaks in Europe where the competent vector is established. Levels of risk and preparedness appear very heterogeneous between and within countries. We believe that ECDC can lend support to EU Member States in preparing for potential local chikungunya outbreaks by building capacity and strengthening networks in collaboration with internationals stakeholders in this global event.
Conflict of interest
None declared.

References
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Antiviral Res. 2010;85(2):328-45. http://dx.doi.org/10.1016/j. antiviral.2009.10.008 2. Cassadou S, Boucau S, Petit-Sinturel M, Huc P, LeparcGoffart I, Ledrans M. Emergence of chikungunya fever on the French side of Saint Martin island, October to December
2013. Euro Surveill. 2014;19(13):pii=20752. http://dx.doi. org/10.2807/1560-7917.ES2014.19.13.20752 3. Schuffenecker I, Iteman I, Michault A, Murri S, Frangeul L,
Vaney MC, et al. Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak. PLoS Med.
2006;3(7):e263. http://dx.doi.org/10.1371/journal. pmed.0030263 4. Mavalankar D, Shastri P, Raman P. Chikungunya epidemic in India: a major public-health disaster. Lancet Infect Dis.
2007;7(5):306-7.
http://dx.doi.org/10.1016/S1473-3099(07)70091-9
5. Rezza G, Nicoletti L, Angelini R, Romi R, Finarelli AC, Panning
M, et al. Infection with chikungunya virus in Italy: an outbreak in a temperate region. Lancet. 2007;370(9602):1840-6. http:// dx.doi.org/10.1016/S0140-6736(07)61779-6 6. Grandadam M, Caro V, Plumet S, Thiberge JM, Souares Y,
Failloux AB, et al. Chikungunya virus, southeastern France.
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Colizza V, et al. Local and regional spread of chikungunya fever in the Americas. Euro Surveill. 2014;19(28):pii=20854.
8. Poletti P, Messeri G, Ajelli M, Vallorani R, Rizzo C, Merler
S. Transmission potential of chikungunya virus and control measures: the case of Italy. PLoS One. 2011;6(5):e18860. http://dx.doi.org/10.1371/journal.pone.0018860 9. Boelle PY, Thomas G, Vergu E, Renault P, Valleron AJ, Flahault
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2014. Available from: http://www.paho.org/hq/index. php?option=com_topics&view=article&id=343&Itemid=40931 11. Paty MC, Six C, Charlet F, Heuzé G, Cochet A, Wiegandt A, et al. Large number of imported chikungunya cases in mainland
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Paturel L, et al. Prospective detection of chikungunya virus in blood donors, Caribbean 2014. Blood. 2014;123(23):3679-81. http://dx.doi.org/10.1182/blood-2014-03-564880 www.eurosurveillance.org

Rapid communications

Dengue virus serotype 4 and chikungunya virus coinfection in a traveller returning from Luanda,
Angola, January 2014
R Parreira (Ricardo@ihmt.unl.pt)1, S Centeno-Lima2, A Lopes1, D Portugal-Calisto3, A Constantino4,5, J Nina3,6
1. Unidade de Microbiologia Médica (Grupo de Virologia) and Unidade de Parasitologia e Microbiologia Médicas (UPMM),
Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisbon, Portugal
2. Unidade de Clínica Tropical and Centro de Malária e Outras Doenças Tropicais (CMDT), Instituto de Higiene e Medicina Tropical
(IHMT), Universidade Nova de Lisboa (UNL), Lisbon, Portugal
3. Unidade de Clínica Tropical IHMT/UNL, Lisbon, Portugal
4. St. Maria Hospital–Centro Hospitalar Lisboa Norte, Lisbon, Portugal
5. São Francisco Xavier Hospital–Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
6. Centro Hospitalar de Lisboa Ocidental/Hospital de Egas Moniz, Lisbon, Portugal
Citation style for this article:
Parreira R, Centeno-Lima S, Lopes A, Portugal-Calisto D, Constantino A, Nina J. Dengue virus serotype 4 and chikungunya virus coinfection in a traveller returning from Luanda, Angola, January 2014. Euro Surveill. 2014;19(10):pii=20730. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20730
Article submitted on 19 February 2014 / published on 13 March 2014

A concurrent dengue virus serotype 4 and chikungunya virus infection was detected in a woman in her early 50s returning to Portugal from Luanda, Angola, in January 2014. The clinical, laboratory and molecular findings, involving phylogenetic analyses of partial viral genomic sequences amplified by RT-PCR, are described. Although the circulation of both dengue and chikungunya viruses in Angola has been previously reported, to our knowledge this is the first time coinfection with both viruses has been detected there.

Detection of coinfection

Here we report the simultaneous detection of chikungunya virus (CHIKV) and dengue virus (DENV) genomes in the peripheral blood of a traveller who returned from
Luanda, Angola, to Portugal in January 2014.
The traveller, a woman in her early 50s, was born and raised in Angola and has lived in Lisbon, Portugal, since the early 1990s. She stayed in Luanda from midDecember 2013 to early January 2014 at her family’s place of residence. There were a large number of mosquitoes in the garden and the patient was repeatedly bitten during her stay.
The patient reported feeling unwell in early January, two days before her return to Portugal. Her condition worsened during the flight, and in the next few days she had high fever (up to 39.5 °C), severe arthralgia, myalgia, prostration and abdominal pain. Three days after her return, she went to the emergency department of a hospital: a malaria blood smear was negative and among a range of laboratory tests (including coagulation speed and levels of glucose, creatinine, bilirubin, aspartate transaminase (AST), alanine transaminase
(ALT), lactate dehydrogenase (LDH), sodium, potassium, chloride ions and C-reactive protein), the only www.eurosurveillance.org abnormal findings were a mildly low platelet count (139
× 109/L; norm: 150–400 × 109/L) and mild leucopenia
(2.9 × 109/L; norm: 4–10 × 109/L). The following day, she went to a hospital specialised in tropical diseases, where photophobia was detected. Further tests were carried out (described below). An arbovirus infection was suspected as the malaria blood smear was persistently negative.
Four days later, the fever had subsided and her condition improved progressively over the next two to three weeks. The patient did not have a rash, conjunctivitis or other clinical signs of a complicated dengue infection (DENV infection with haemorrhage); indeed, she had no other abnormal clinical signs at all during the course of her illness. To the best of her knowledge, none of her family or neighbours in Luanda experienced a similar illness.

Laboratory findings

Four days after her return from Luanda, DENV nonstructural (NS) protein 1 and anti-CHIKV IgM were detected
(through the use of SD BIOLINE Dengue Duo NS1 Ag
+ Ab Combo and SD Bioline Chikungunya IgM), while
DENV-specific IgM and IgG were not detected. Two days later, the same tests were performed: anti-CHIKV
IgM and DENV-specific IgM and IgG were detected, but DENV NS1 was not. Using RNA extracted from the blood sample where NS1 had been found, detection of the viral genomes was carried out either by a nested
RT-PCR as previously described [1,2] or by using primers that target the virus packaging sequence [3]. The sizes of the amplicons obtained were compatible with the presence of both DENV4 (approximately 390 bp, covering the C-prM region) and CHIKV (approximately
350 bp, in the NS2 coding region).

9

Additional molecular confirmation was obtained by performing phylogenetic analyses of the sequence of both amplicons (deposited in the GenBank/European
Molecular Biology Laboratory (EMBL)/DNA DataBank of Japan (DDBJ) databases under accession numbers
AB908053 and AB908054) using the using GTR+G+I model [4]. The DENV sequence obtained clearly clustered with DENV4 reference strains (Figure 1), while the
CHIKV sequence segregated with those included in the
Central/Eastern/Southern African genotype (Figure 2).
Despite the presence of both viral genomes in the same blood sample, the viraemia dropped rapidly below the detection level, as both DENV and CHIKV RNA could not be detected in blood collected 48 hours later.

Figure 1
Maximum likelihood phylogenetic tree analysis of dengue virus (DENV) serotypes 1–4 C-prM sequences
DENV4 VE/BID -V2194/2001

FJ639764

DENV4 VE/BID -V1161/2007

EU854301

DENV4 D4.46 1998

AY152072

DENV4 US/BID -V1082/1998

FJ024424

DENV4 H778494 JQ513335
DENV4 VE 61013 2007

HQ332175

DENV4 VE/BID -V2492/2007

FJ882583

DENV4 US/BID -V1094/1998

EU854297

DENV4 VE/BID -V2166/1998

FJ639739

DENV4 D4.20 1998 AY152036
DENV4 H780120 JQ513341
DENV4 H780563 JQ513343
DENV4 H779228

Background

JQ513338

DENV4 VE/BID -V2491/2007 FJ882582

Dengue has developed into a worldwide public health problem, especially over the last 50 years [5,6]. More recently, the impact of other arboviruses on human health has followed a similar trend [7]. This is true for
CHIKV, which, since 2004, has been an emerging pathogen, causing large outbreaks in many islands in the
Indian Ocean and in the Indian subcontinent, where, in 2005-2006 alone, well over a million cases of CHIKV infection were reported from different states [8].

DENV4 VE/BID -V2490/2007 FJ882581
DENV4 RP/BR/2011/131 JN712226
DENV4 SJRP/BR/2011/167 JN712225
DENV4 Luanda 2014 AB908053

77

DENV4 Br246RR/10 JN983813
DENV4 CO/BID -V3410/2004 GQ868583
DENV4 D4.29 1992 AY152200
DENV4 D4/PR/97/JAN -1991 GU318309
DENV4 CO/BID -V1600/1997 FJ024476
DENV4 D4M.24 1982 AY152308
DENV4 VE/BID -V2610/2007 GQ199876
DENV4 INDIA G11337JF262783

The majority of DENV infections occur in the Asia–
Pacific and Americas–Caribbean regions [5], while
CHIKV is endemic to countries in Africa and Asia [9].
In Africa, the epidemiology and public health impact of both viruses is far from clear, but the wide geographical distribution of their primary vectors (Aedes aegypti and Aedes albopictus), rapid human population growth, unplanned urbanisation, and increased international travel make their transmission likely [10,11]. Moreover, as the clinical features of DENV and CHIKV are similar, CHIKV infections usually go undiagnosed in areas where DENV circulates [11]. Furthermore, where malaria is also endemic and the majority of febrile illnesses are diagnosed as such, often without laboratory confirmation, both viral infections may go undetected [12].

DENV4 Taiwan -2K0713

85

AY77633

DENV4 SG/06K2270DK1/2005GQ39825
DENV4 PH/BID -V3361/1956GQ868594
DENV4 Guangzhou B5 AF289029
DENV4 ThD4 0087 77

AY618991

DENV4 ThD4 0348 91

99

AY618990

99 DENV4 H781363 JQ513345

DENV4 Singapore 8976/95 AY762085
99

DENV4 P75 -514 JF262779
99 DENV4 P75 -215 EF457906

DENV4 ThD4 0017 97 AY618989
DENV4 ThD4 0476 97 AY618988
99 DENV2 HM582105

DENV2 JX470186
97

DENV1 AF298807
DENV1 AF311956

78

DENV3 AY662691
99 DENV3 AY679147

0.2

Although CHIKV/DENV coinfections were first reported in India in 1967 [13] and later confirmed in Sri Lanka
(2008), Malaysia (2010) and Gabon (2007) [14-16], these coinfections are rarely notified.

Discussion

Serological reports from the 1960s [17], the detection of DENV in travellers returning from Angola in the
1980s [10], and the detection of DENV1 and DENV2 in travellers in the 1980s and in 1999–2002 [10,18] suggest endemic DENV activity in Angola. As far as CHIKV is concerned, the situation is a lot less clear. However, serological studies from the 1960s not only identified the presence of anti-CHIKV neutralising antibodies in the north of the country, but also allowed the isolation of two strains from a viraemic individual and wild-caught mosquitoes during an outbreak of Kâtolu
Tôlu (Kimbundu dialect for ‘break-bone disease’),

10

The tree was constructed using the using the GTR+Γ+I model [4].
The amplicon isolated from the patient is shown in bold. Reference strains, downloaded from public databases, are identified by strain name and accession number (DENV4) or simply by viral serotype and accession number (DENV1–3). The numbers at specific branches indicate bootstrap values (only values ≥77% are indicated). a dengue-like disease caused by the CHIKV, which occurred in Luanda in 1970 [19].
The detection of DENV4 in the recent traveller is of interest, given that on 1 April 2013, the Angolan health authorities reported a dengue outbreak in the country
[20], which was later shown to have been caused by
DENV1 [21], and the current description of DENV4 in

www.eurosurveillance.org

Figure 2
Maximum likelihood phylogenetic tree of chikungunya virus (CHIKV) partial nonstructural protein (NS) 2 sequences
CHIKV 0810aTwFJ807898
CHIKV RGCB356/KL08GQ428215
CHIKV D570/06EF012359
CHIKV SL10571AB455494
CHIKV Wuerzburg 1EU037962
96 CHIKV 0611aTw
FJ807896

CHIKV SGEHICHD122508FJ445502
CHIKV IND-06-RJ1EF027137
CHIKV LR2006 OPY1DQ443544

81

East /Central/Southern African genotype CHIKV TM25EU564334
CHIKV KPA15HQ456254
CHIKV Angola M2022HM045823

75

CHIKV DakAr B 16878HM045784
CHIKV IND-00-MH4EF027139
100

CHIKV RossAF490259
97 CHIKVNC_004162

CHIKV Luanda 2014AB908054
CHIKV AF15561EF452493
CHIKV IND-63-WB1EF027140
97

CHIKV JKT23574HM045791

Asian genotype

CHIKV MY002IMR/06/BPEU703759
CHIKV IbH35HM045786
98 CHIKV 37997AY726732

West African genotype
O’nyong-nyong virusNC_001512

100

O’nyong-nyong virus SG650AF079456

0.02

The tree was constructed using the using the GTR+Γ+I model [4]. The amplicon isolated from the patient is shown in bold. Reference strains are indicated by strain name and accession number. The three CHIKV genotypes (East/Central/Southern African, West African and Asian) are indicated. The numbers at specific branches indicate bootstrap values (values ≥75% are indicated).Two strains of o’nyong nyong virus, the
Alphavirus most closely related to CHIKV, have been used as an outgroup.

Luanda may indicate the circulation of multiple DENV subtypes in the country.
Although clinical examination of CHIKV/DENV coinfected patients has not yet allowed the identification of specific or severe symptoms, such observations should be interpreted with caution in view of the limited number of clinical and biological investigations reported. Our findings may add to the recognition of
CHIKV/DENV coinfections and suggest that tests to detect the presence of both viruses should be carried out in individuals showing clinical signs of an infection with either CHIKV or DENV.

www.eurosurveillance.org

Conflict of interest
None declared.

Authors’ contributions
Ricardo Parreira: molecular analyses and manuscript writing. Ângela Mendes: molecular analyses. Jaime Nina: clinical diagnosis and manuscript writing. Antónia Constantino: clinical diagnosis and manuscript writing. Sónia CentenoLima and Daniela Portugal Calisto: laboratory diagnosis and manuscript writing.

11

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www.eurosurveillance.org

Rapid communications

Emergence of chikungunya fever on the French side of
Saint Martin island, October to December 2013
S Cassadou (sylvie.cassadou@ars.sante.fr)1, S Boucau2, M Petit-Sinturel1, P Huc3, I Leparc-Goffart 4 , M Ledrans1
1. French Institute for Public Health Surveillance (InVS), Paris, France
2. Regional Health Agency of Guadeloupe, Saint Martin and Saint Barthélemy, France
3. Laboratory ‘Biocaraïbes’ – Saint Martin, France
4. French National Reference Centre for Arboviruses, Armed Forces Biomedical Research Institute (IRBA), Marseille, France
Citation style for this article:
Cassadou S, Boucau S, Petit-Sinturel M, Huc P, Leparc-Goffart I, Ledrans M. Emergence of chikungunya fever on the French side of Saint Martin island, October to
December 2013. Euro Surveill. 2014;19(13):pii=20752. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20752
Article submitted on 20 February 2014 / published on 3 April 2014

On 18 November 2013, five residents of Saint Martin presented with severe joint pain after an acute episode of dengue-like fever. Epidemiological, laboratory and entomological investigations provided evidence of the first autochthonous transmission of chikungunya virus in the Americas. The event indicates a risk of epidemics in America and Europe through substantial passenger traffic to and from continental France.
We describe detection and confirmation of the first six cases and results of the first weeks of surveillance.
On 16 and 18 November 2013, through health event intelligence, separate signals from two sources, a patient and a hospital practitioner, reached Public
Health Nurse (PHN) and epidemiologists, respectively.
Five residents of a Saint Martin district called Oyster
Pond, which straddles the two sides of the island, presented with severe joint pain after an acute episode of dengue-like fever. Following the alerts, two investigations were carried out in Oyster Pond.

Detection and confirmation of the first six cases: health event activity
Epidemiological surveillance and health event activities on Saint Martin before the outbreak

Saint Martin and Sint-Maarten are parts of the same
Caribbean island and are, respectively, French and
Dutch overseas territories. Epidemiological surveillance and health event intelligence activities on the
French side are performed through a network of health professionals including epidemiologists from the
French Institute for Public Health Surveillance (Cire), public health nurses (PHN) from the Regional Agency for Health (ARS), hospital and general practitioners, local laboratory and professionals of vector control.
This network has been in place for many years to monitor, for example, the epidemiology of dengue fever that is endemo-epidemic in the French West Indies [1].

www.eurosurveillance.org

Investigations following the first signal of the health event

On 21 and 22 November 2013, standardised interviews and an entomological survey were conducted in the
Oyster Pond district. In addition to the first five notified patients, three further patients were detected during the investigations in the district and, finally, eight patients were interviewed: five women and three men whose age ranged from 49 to 73 years. Their dates of symptom onset ranged from 15 October to 12
November; fever was acute, with a high temperature ranging from 38.8 to 39.5 °C. Five patients reported rashes (erythema, maculae, papules and, in one case, vesicles). All eight had incapacitating pain, most often in the joints of hands or feet, preventing day-to-day activities. Seven patients also had oedema in the painful joints. Available laboratory data suggested a viral infection because of a normal white cell blood count and a normal level of C-reactive protein, but the specific laboratory tests to confirm dengue fever were negative
(IgM and NS1 test) [2-3]. None of the patients reported travelling to countries other than continental France, the Virgin Islands, the United States and Germany, all countries unaffected by chikungunya virus (CHIKV).
A dengue epidemic was ongoing on Saint-Martin at the time, and the vector (Aedes aegypti) was present on the island. The entomological investigation following the signal showed a higher density of these mosquitoes in the Oyster Pond district compared with other areas. This observation made a mosquito-borne disease plausible, but the negative laboratory tests suggested a cause other than dengue virus (DENV).
Blood samples of the eight patients were tested in the French National Reference Centre for Arboviruses in Marseille, mainland France. On 2 December 2013, serology results for two cases were positive for CHIKV
(IgM). A first positive RT-PCR [4] result for another case was received on 5 December. Overall, six of the eight suspected cases could by laboratory-confirmed: four had positive IgM tests, one had a positive RT-PCR, one
13

04 Dec

02 Dec

30 Nov

28 Nov

26 Nov

24 Nov

22 Nov

20 Nov

18 Nov

16 Nov

14 Nov

12 Nov

10 Nov

08 Nov

06 Nov

04 Nov

02 Nov

31 Oct

29 Oct

27 Oct

Probable (IgM)

25 Oct

23 Oct

21 Oct

19 Oct

17 Oct

13 Oct

11 Oct

09 Oct

07 Oct

15 Oct

Confirmed (RT-PCR)

Negative

4
3
2
1
0
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Number of cases

Figure
Epidemic curve of chikungunya fever cases by date of symptom onset, Saint Martin, 5 October–4 December 2013 (n=26)

Date 2013

had positive results in both tests. The remaining two patients were negative in both tests. The six confirmed cases were classified as autochthonous, since they had no travel history to countries affected by CHIKV.
Diagnostic tests for DENV were negative for all six.
The full-length viral RNA genome was characterised by the French National Reference Centre for Arboviruses, in Marseille. Importantly, the virus did not belong to the East Central South African genotype but to the
Asian genotype, phylogenetically related to a number of strains recently identified in Asia (Indonesia 2007,
China 2012 and the Philippines 2013) [5].

Detection of later cases
Improvement of surveillance

After the confirmation of virus circulation on Saint
Martin, the following four objectives were established for future chikungunya surveillance: detect all new suspected cases in a timely manner, collect epidemiological data, confirm cases by laboratory tests and monitor the spread of the disease on the French side of Saint
Martin. Collaboration with the Dutch side of the island was also enhanced with meetings and data exchange, although the preparedness plan did not specifically include such actions.
The definition for a suspected case of chikungunya fever was sent to all hospitals and general practitioners as follows: (i) a patient with onset of acute fever
>38.5 °C and with at least one of the following symptoms (headache, retro-orbital pain, myalgia, arthralgia, lower back pain) and who had visited an epidemic or endemic area, or (ii) a patient with acute fever >38.5
°C and severe arthralgia of hands or feet not explained by another medical condition.
For laboratory confirmation, it was recommended that doctors request simultaneous tests for dengue and
CHIKV for all patients fulfilling the case definition. The laboratory in charge of taking blood samples had to fill in a form including the date of symptom onset, date of sample, the address and phone number of the patient.
These data were transmitted to epidemiologists and vector control staff. Spatial distribution of the cases
14

was analysed using the addresses provided for all patients. As for the first detected cases, all blood samples collected during this second phase of surveillance had to be sent to the National Reference Laboratory in
Marseille, France. The laboratory results allowed classification of the clinical suspected cases as follows: invalidated case if all the tests were negative, probable case if only serology (IgM) was positive, confirmed case if RT-PCR was positive, confirmed co-infection if
RT-PCR was positive for dengue and CHIKV in the same sample. Overall results for all 26 suspected cases with laboratory test by 4 December 2013

The epidemic curve (Figure) summarises, by date of symptom onset, the first 26 patients tested between
5 of October and 4 December 2013. These include the first eight patients described above as well as a further
18 suspected cases with available laboratory test. Of those 26, 20 were identified as probable or confirmed cases. Seven probable or confirmed patients were male and 13 were female; the median age was 50 years
(range 6–72 years). No patient had to be hospitalised.
In addition to these 26 patients, 10 were seen by a doctor who considered that their symptoms fulfilled the criteria of a suspected case, but these patients, probably because of a mild condition, did not go to the laboratory for blood sample taking.
The period of approximately two weeks between the first confirmed case and the subsequent two confirmed cases is consistent with the time required for the contamination of a mosquito, the extrinsic cycle of the virus in this mosquito, the stinging of another patient by this infected mosquito and the incubation period in the new patient. This temporal pattern was repeated for the later groups of probable and confirmed cases occurring in November 2013.

Discussion and conclusion

Epidemiological, laboratory and entomological investigations of the first cases provided evidence for the first active transmission of CHIKV in the Americas.

www.eurosurveillance.org

At the time of the investigations, information available about the international epidemiological situation of chikungunya fever was scarce. During 2013, cases had been reported in Bali, Indonesia, Java, the Pacific
Ocean (Micronesia, New Caledonia), the Philippines and
Singapore [6]. Several states in India (Gujarat, Kerala,
Nad, Odisha and Tamil) also reported an increased number of cases [7]. This is of relevance because of the substantial passenger traffic between the Indian community of Saint Martin and India, and indicates a risk of importing cases from India.
The timeliness of the alert, despite the simultaneous dengue fever epidemic, was made possible by three factors. The first was the health event intelligence system organised in the French West Indies, which aims to confirm and assess the risk of every unusual health signal transmitted (via telephone or email) by a health professional or a patient [8].
The second was the awareness of the risk of introduction and transmission of CHIKV on all Caribbean islands, since the major epidemic on Reunion Island in 2006 [9]. Between 2006 and 2009, nine travellers entering the French West Indies were diagnosed with confirmed CHIKV infection, one of them on Saint Martin
[10]. Seven of them had arrived from Reunion Island and two from India. Vector control activities were implemented around each of these imported cases, and none led to local transmission. Although Girod and Coll confirmed vector competence of Ae. aegypti
(the only vector mosquito genus present in the French
West Indies) for CHIKV transmission [11], no indigenous transmission of this virus had been observed in the
Americas since [12].
The third factor of timeliness was the chikungunya preparedness plan which is similar to that for DENV, integrating activities of surveillance, laboratory, communication, patient care and vector control. Following the alert of 2006 and the risk of virus spread from potential other imported cases, the Cire and ARS teams of all the French territories in the Americas had decided to implement a preparedness and response plan for
CHIKV introduction. Suspected and confirmed case definitions were standardised, laboratory resources for confirmation identified in the region, and first response activities implemented. This plan (‘Programme de
Surveillance, d’Alerte et de Gestion’ (Psage)), based on the Integrated Management Strategy recommended by the World Health Organization for DENV, included four phases of increasing epidemic risk. At the time of the outbreak in 2013, Saint Martin was in the first risk phase, which required reporting of suspected and confirmed cases of CHIKV by clinicians and diagnostic laboratories to the local Health Event-dedicated cell of the corresponding Regional Agency for Health (Martinique,
Guadeloupe or French Guiana). Epidemiological and entomological investigations were to be conducted simultaneously in the neighbourhood of the reported cases. www.eurosurveillance.org

This regional alert has a wider impact: if the epidemic continues to spread in the Caribbean region and the
Americas during the coming months, imported cases in southern Europe may have the potential to cause local outbreaks during the summer season.
Conflict of interest
None declared.

Authors’ contributions
Sylvie Cassadou and Martine Ledrans: management and coordination of the investigations. Severine Boucau: implementation of investigations. Marion Petit-Sinturel: data management. Patricia Huc: blood sample taking and management. Isabelle Leparc-Goffart: Chikungunya tests (RTPCR and Serology).

References
1. Quénel P, Rosine J, Cassadou S, Ardillon V, Blateau A, Matheus
S, et al. Épidémiologie de la dengue dans les Départements français d’Amérique. [Epidemiology of dengue in the French overseas departments of the Americas]. Bull Epidémiol Hebd.
2011;33-34:358-63. French. Available from: http://www.invs. sante.fr/content/download/18602/117933/version/5/file/ BEH_33_34_2011.pdf
2. Dussart P, Petit L, Labeau B, Bremand L, Leduc A, Moua D, et al. Evaluation of two new commercial tests for the diagnosis of acute dengue virus infection using NS1 antigen detection in human serum. PLoS Negl Trop Dis. 2008;2(8):e280. http://dx.doi.org/10.1371/journal.pntd.0000280 3. Tricou V, Vu HT, Quynh NV, Nguyen CV, Tran HT, Farrar J, et al. Comparison of two dengue NS1 rapid tests for sensitivity, specificity and relationship to viraemia and antibody responses. BMC Infect Dis. 2010;10:150. http://dx.doi.org/10.1186/1471-2334-10-142 4. Marchand E, Prat C, Jeannin C, Lafont E, Bergmann T, Flusin O, et al. Autochthonous case of dengue in France, October 2013.
Euro Surveill. 2013;18(50):pii=20661.
5. Leparc-Goffart I, Nougairede A, Cassadou S, Prat C, de
Lamballerie X. Chikungunya in the Americas. Lancet.
2014;383(9916):514.
http://dx.doi.org/10.1016/S0140-6736(14)60185-9
6. Institut de Veille Sanitaire (InVS). Bulletin hebdomadaire international no 428 du 27 novembre au 3 décembre. Paris:
InVS; 2013. French. Available from: http://www.invs.sante.fr/ fr/Publications-et-outils/Bulletin-hebdomadaire-international/ Tous-les-numeros/2013/Bulletin-hebdomadaire-internationaldu-27-novembre-au-3-decembre-2013.-N-428
7. Cellule interrégionale d’épidémiologie (Cire) Océan Indien.
Situation de la dengue et du chikungunya à la Réunion.
[Situation of dengue and chikungunya on Reunion Island].
Point épidémiologique. 2013;46:1-2. French. Available from: http://www.invs.sante.fr/fr/Publications-et-outils/Pointsepidemiologiques/Tous-les-numeros/Ocean-Indien/2013/ Surveillance-des-arboviroses-a-la-Reunion.-Point-au-20novembre-2013
8. Cellule interrégionale d’épidémiologie (Cire) AntillesGuyane. Le nouveau dispositif de veille sanitaire des Antilles
Guyane. [The new system for health event intelligence on the West Indies and French Guiana]. Bulletin de veille sanitaire. 2011;4:1-21. French. Available from: http:// www.invs.sante.fr/fr/Publications-et-outils/Bulletinde-veille-sanitaire/Tous-les-numeros/Antilles-Guyane/ Bulletin-de-veille-sanitaire-Antilles-Guyane.-n-4-avril-2011
9. Renault P, Solet JL, Sissoko D, Balleydier E, Larrieu S, Filleul
L, et al. A major epidemic of chikungunya virus infection on Réunion Island, France, 2005-2006. Am J Trop Med Hyg.
2007;77(4):727-31.
10. Cellule interrégionale d’épidémiologie (Cire) Antilles-Guyane.
Surveillance et gestion du risqué d’émergence du virus
Chikungunya d’émergence du virus Chikungunya aux Antilles et en Guyane Française. [Monitoring and management of the risk of emergence of chikungunya virus in the West Indies and
French Guiana]. Bulletin d’Alerte et de Surveillance Antilles

15

Guyane. 2006;2:1-6. French. Available from: http://www.invs. sante.fr/publications/basag/basag2006-2.pdf 11. Girod R, Gaborit P, Marrama L, Etienne M, Ramdini C,
Rakotoarivony I, et al. Viewpoint: High susceptibility to
Chikungunya virus of Aedes aegypti from the French West
Indies and French Guiana. Trop Med Int Health. 2011;16(1):1349. http://dx.doi.org/10.1111/j.1365-3156.2010.02613.x 12. Pan American Health Organization (PAHO). Preparedness and
Response for Chikungunya Virus: Introduction in the Americas.
Washington, D.C.: PAHO; 2011. Available from: http://www. paho.org/hq/index.php?option=com_docman&task=doc_ download&gid=16984&Itemid

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www.eurosurveillance.org

Rapid communications

Importance of case definition to monitor ongoing outbreak of chikungunya virus on a background of actively circulating dengue virus, St Martin, December
2013 to January 2014
R Omarjee1, C M Prat1, O Flusin1, S Boucau2, B Tenebray1, O Merle1, P Huc-Anais3, S Cassadou4 , I Leparc-Goffart (isabelle. leparcgoffart@gmail.com)1 1. IRBA, French National Reference Center for Arboviruses, Marseille, France
2. Affaires Sanitaires et Sociales (ARS), Délégation territoriale de Saint Martin et Saint Barthélemy, Saint Martin, France
3. Laboratory Saint-Martin Biologie Philippe Chenal, Saint Martin, France
4. French Institute for Public Health Surveillance, Paris France
Citation style for this article:
Omarjee R, Prat CM, Flusin O, Boucau S, Tenebray B, Merle O, Huc-Anais P, Cassadou S, Leparc-Goffart I. Importance of case definition to monitor ongoing outbreak of chikungunya virus on a background of actively circulating dengue virus, St Martin, December 2013 to January 2014. Euro Surveill. 2014;19(13):pii=20753.
Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20753
Article submitted on 24 March 2014 / published on 3 April 2014

Since 5 December 2013, chikungunya virus (CHIKV) has been demonstrated to circulate in the Caribbean, particularly on Saint Martin. This region is facing a concomitant dengue virus (DENV) outbreak. Of 1,502 suspected chikungunya cases, 38% were confirmed chikungunya and 4% confirmed dengue cases, with three circulating serotypes. We report in addition 2.8%
CHIKV and DENV co-infections. This study highlights the importance of the case definition for clinicians to efficiently discriminate between DENV infection and
CHIKV infection.
On 5 December 2013, the first confirmed autochthonous cases of chikungunya virus (CHIKV) infection were reported in the Caribbean, on the island of Saint
Martin, by the French National Reference Center for
Arboviruses (IRBA, Marseille) [1]. Before that time, only imported cases of Chikungunya had been detected in the Americas.
CHIKV is a mosquito-transmitted virus (arbovirus) of the Togaviridae family and Alphavirus genus. It was first isolated from humans and mosquitoes in 1952/53 during an epidemic of febrile polyarthralgia in Tanzania
[2]. CHIKV is endemic in some parts of Africa and causes recurrent epidemic waves in Asia and on the
Indian subcontinent.
The Caribbean region, with tropical climate and the presence of Aedes aegypti mosquito vectors is endemic for dengue virus (DENV), another arbovirus. Since the re-emergence of dengue in the Caribbean subregion in the 1970s and the first dengue outbreak identified on
Saint Martin in 1977, this arbovirus has been responsible for multiple waves of outbreaks on this island [3].

www.eurosurveillance.org

The latest epidemic of DENV on the island started in
January 2013.
Both chikungunya and dengue disease have similar clinical symptoms, which makes the clinical diagnosis complex, although differences exist. In the context of an emerging virus in a region where another arbovirus is already endemic and actively circulating, the case definition (Table 1) is crucial to follow the dynamics of the new outbreak. This report shows the efficiency of the established case definition in the chikungunya outbreak on Saint Martin, and presents the incidence of co-infection of DENV and CHIKV.

Virological findings during the chikungunya and dengue outbreak

The French National Reference Centre for Arboviruses in Marseille received all samples from Saint Martin fitting the CHIKV case definition. However, both DENV and

Table 1
Case definition for clinical suspected chikungunya and dengue cases, Saint Martin, 2013
Chikungunya virus infection Dengue virus infection

Fever higher than 38.5
°C of sudden onset

Fever higher than 38.5 °C of sudden onset Articular pain in extremities At least one of the following clinical signs: headache, arthralgia, myalgia, back pain, retro-orbital pain, musculoarticular pain

Absence of other aetiological causes

Absence of other aetiological causes

17

Table 2
Strategy for laboratory diagnosis of chikungunya and dengue virus infection, Saint Martin, 2013
Period between start date of clinical symptoms and sample date Laboratory tests performed

7 days

Serology

CHIKV diagnosis was done on every sample because of the local epidemiological context and the clinical similarities between the two diseases. According to the date of clinical symptoms onset and the sampling date, viral genome and/or IgM and IgG detection techniques were performed following the strategy described in Table 2, by using, respectively, real-time RT-PCR described previously [4,5] and in-house ELISA (MAC
ELISA for IgM and indirect IgG ELISA) [6]. The samples were mostly early samples, with 87% of samples taken less than seven days after the onset of symptoms.
The virological results are presented in Figure 1. A total of 1,502 suspected chikungunya cases samples were received between week 43 of 2013 (4 December 2013) and week 05 of 2014 (31 January 2014). Of those, 570 were confirmed chikungunya cases (38%), and 65 were confirmed dengue cases (4%). Confirmed cases were defined as patients with RT-PCR-positive or IgM- and
IgG-positive samples. The median age of confirmed chikungunya cases was 39 (range: 10 days–73) and
60% were female. There were only three severe cases which required hospitalisation.

that CHIKV circulation has been demonstrated in the
Caribbean area and, more generally, the Americas. The genome of this circulating CHIKV strain was sequenced and belongs to the Asian genotype, suggesting Asia as the probable origin for the circulating virus [7].
The concomitant presence of DENV on this island leads to a difficult differential diagnosis for clinicians because both infections have similar clinical signs.
Here, shortly after the start of the outbreak, an efficient case definition was set up that allowed monitoring of the emerging CHIKV outbreak on the background of actively circulating DENV.
A non-negligible proportion of co-infections were identified. Patients co-infected with CHIKV and DENV were previously reported in India, South-East Asia and Africa
[8-10]. During the chikungunya epidemic in Gabon in
2007, a total of 3% of CHIKV-infected patients were also infected with DENV, both viruses being detected by RT-PCR. The CHIKV strain in Gabon belonged to the
East Central South African genotype, contrary to the present Saint Martin virus, which belongs to the Asian
Figure 1
Confirmed chikungunya (n=570) and dengue (n=65) cases, Saint Martin, 4 December 2013–31 January 2014
120

Confirmed dengue cases

100

In Saint Martin, three serotypes of DENV co-circulated during this outbreak: DENV1, DENV2 and DENV4, with serotype 1 predominating. The proportion of the different DENV serotypes detected during this period is presented in Figure 2.

80

Number of cases

There were an additional 16 patients with confirmed co-infection of CHIKV and DENV (not included in Figure
1), i.e. with both viral genomes detected in the same blood sample. Those cases corresponded to the clinical case definition (Table 1) and were not severe cases.
The co-infecting DENV was predominantly serotype
1, following the distribution observed in the monoinfected patients with 10 DENV1, two DENV2 and four
DENV4 infections. Of these co-infected cases, four patients were two pairs of relatives living at the same address. Confirmed chikungunya cases

60

40

20

Discussion

The Caribbean region is currently facing an epidemic of CHIKV that started on Saint Martin and spread to
Saint Barthelemy, Martinique, Guadeloupe and the
Virgin Islands within a few weeks. This is the first time
18

0

43

44

45

46

47

48

49

50

51

52

1

2

3

4

5

Week 2013/14

www.eurosurveillance.org

Figure 2
Distribution of circulating dengue virus serotypes, Saint
Martin, 4 December 2013 to 31 January 2014 (n=78)
50

45

Both emergences of dengue virus in France in 2010 and
2013 started with the arrival of a viraemic patient from the French Caribbean, which reflects the considerable exchange between Europe and the Caribbean [11,12].
The current chikungunya outbreak in the Caribbean likewise presents a threat of emergence of this disease in European countries, where the vector Aedes albopictus is already established.
Authors’ contributions

40

RO, CMP, OF, SB, BT, OM, PH-A, SC and ILG participate to the study; RO, CMP, OF, ILG wrote the manuscript; PH-A and SC reviewed the manuscript.
35

Conflict of interest:
None declared.

30

Number of cases

References
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10

5

0

DENV-1

DENV-2

DENV-3

DENV-4

Dengue virus serotypes

genotype. However, the number of co-infected cases in this current outbreak follows the same pattern, with
2.8% of CHIKV-infected patients also infected by DENV.
This study documents the importance of a clear case definition set up for clinicians to efficiently discriminate between DENV infection and CHIKV infection, thereby allowing good monitoring of the emerging outbreak by health authorities. With the presence of
Aedes mosquitos in most of the Americas, and intense circulation of the human population in this area, it is predicted that CHIKV will spread, and most probably in
DENV-endemic areas. www.eurosurveillance.org 1. Cassadou S, Boucau S, Petit-Sinturel M, Huc P, Leparc-Goffart
I, Ledrans M. Emergence of chikungunya fever on the French side of Saint Martin island, October to December 2013. Euro
Surveill. 2014;19(13):pii=20752.
2. Robinson M. An epidemic of virus disease in Southern
Province, Tanganyika Territory, in 1952–53. I. Clinical features.
Trans R Soc Trop Med Hyg. 1955;49(1):28-32. http://dx.doi. org/10.1016/0035-9203(55)90080-8 3. Van der Sar A, Woodall JP, Temmer LE. The dengue epidemic in the Leeward Islands of the Netherlands Antilles: Saba,
St. Eustatius, and St. Martin, 1977. In: PAHO Scientific pub.
Dengue in the Caribbean. Washington, DC: Pan American
Health Organization; 1977. p. 55-9.
4. Pastorino B, Bessaud M, Grandadam M, Murri S, Tolou HJ,
Peyrefitte CN. Development of a TaqMan RT-PCR assay without
RNA extraction step for the detection and quantification of
African Chikungunya viruses. J Virol Methods. 2005;124(12):65-71. http://dx.doi.org/10.1016/j.jviromet.2004.11.002
5. Leparc-Goffart I, Baragatti M, Temmam S, Tuiskunen A,
Moureau G, Charrel R, et al. Development and validation of real-time one-step reverse transcription-PCR for the detection and typing of dengue viruses. J Clin Virol. 2009;45(1):61-6. http://dx.doi.org/10.1016/j.jcv.2009.02.010 6. Marchand E, Prat C, Jeannin C, Lafont E, Bergmann T, Flusin O, et al. Autochthonous case of dengue in France, October 2013.
Euro Surveill. 2013;18(50):pii=20661.
7. Leparc-Goffart I, Nougairede A, Cassadou S, Prat C, de
Lamballerie X. Chikungunya in the Americas. Lancet.
2014;383(9916):514.
http://dx.doi.org/10.1016/S0140-6736(14)60185-9
8. Chahar HS, Bharaj P, Dar L, Guleria R, Kabra SK, Broor S. Coinfections with hikungunya virus and dengue virus in Delhi,
India. Emerg Infect Dis. 2009;15(7):1077-80. http://dx.doi. org/10.3201/eid1507.080638 9. Leroy EM, Nkoghe D, Ollomo B, Nze-Nkogue C, Becquart P,
Grard G, et al. Concurrent chikungunya and dengue virus infections during simultaneous outbreaks, Gabon, 2007.
Emerg Infect Dis. 2009;15(4):591-3. http://dx.doi.org/10.3201/ eid1504.080664 10. Chang SF, Su CL, Shu PY, Yang CF, Liao TL, Cheng CH, et al. Concurrent Isolation of Chikungunya Virus and Dengue
Virus from a Patient with Coinfection Resulting from a Trip to
Singapore. J Clin Microbiol. 2010;48(12):4586-9. http://dx.doi. org/10.1128/JCM.01228-10 11. La Ruche G, Souarès Y, Armengaud A, Peloux-Petiot F,
Delaunay P, Desprès P, et al. First two autochthonous dengue virus infections in metropolitan France, September 2010. Euro
Surveill. 2010;15(39):pii=19676.
12. Marchand E, Prat C, Jeannin C, Lafont E, Bergmann T, Flusin O, et al. Autochthonous case of dengue in France, October 2013.
Euro Surveill. 2013;18(50):pii=20661.

19

Rapid communications

Cases of chikungunya virus infection in travellers returning to Spain from Haiti or Dominican Republic,
April-June 2014
A Requena-Méndez (ana.requena@cresib.cat)1,2, C García2,3, E Aldasoro1, J A Vicente3, M J Martínez4 , J A Pérez-Molina5, A CalvoCano1, L Franco6, I Parrón7, A Molina3, M Ruiz3, J Álvarez7, M P Sánchez-Seco6, J Gascón1
1. Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Spain
2. These authors contributed equally to this work
3. Internal Medicine Department, Hospital Virgen de la Luz, Cuenca, Spain
4. Microbiology Laboratory, Barcelona Centre for International Health Research
5. Tropical Medicine & Clinical Parasitology. Infectious Diseases Department, Hospital Ramón y Cajal, IRYCIS, Madrid, Spain
6. National Microbiologic Center. Virology and imported arbovirus department, ISCIII, Madrid, Spain
7. Unitat de Vigilància Epidemiològica Barcelonès Nord Maresme. Agència de Salut Pública de Catalunya. Barcelona, Spain
Citation style for this article:
Requena-Méndez A, García C, Aldasoro E, Vicente JA, Martínez MJ, Pérez-Molina JA, Calvo-Cano A, Franco L, Parrón I, Molina A, Ruiz M, Álvarez J, SánchezSeco MP, Gascón J. Cases of chikungunya virus infection in travellers returning to Spain from Haiti or Dominican Republic, April-June 2014 . Euro Surveill.
2014;19(28):pii=20853. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20853
Article submitted on 08 July 2014 / published on 17 July 2014

Ten cases of chikungunya were diagnosed in Spanish travellers returning from Haiti (n=2), the Dominican
Republic (n=7) or from both countries (n=1) between
April and June 2014. These cases remind clinicians to consider chikungunya in European travellers presenting with febrile illness and arthralgia, who are returning from the Caribbean region and Central America, particularly from Haiti and the Dominican Republic.
The presence of Aedes albopictus together with viraemic patients could potentially lead to autochthonous transmission of chikungunya virus in southern Europe.
We report 10 cases diagnosed with chikungunya virus
(CHIKV) infection in Spain after returning from Haiti or the Dominican Republic. These are the first cases reported in Spain from travellers returning from Latin
America and this should alert clinicians to consider
CHIKV infection in any traveller with febrile illness or arthralgia returning from Central America and/or the
Caribbean, particularly from Haiti and the Dominican
Republic.

Case reports
Case definition

In this report, a probable case was defined as a person who was residing in or visited epidemic area within 15 days before onset of symptoms, was presenting with fever and arthralgia or arthritis, and had a positive
IgM CHIKV antibody test result; a confirmed case was defined as a positive tests for one of the laboratory criteria, irrespective of clinical manifestations: (i) presence of viral RNA, (ii) specific IgM antibodies or (iii) four-fold increase in IgG titres in paired samples.

20

Clinical and epidemiological data

Between April and June 2014, 10 patients were diagnosed with chikungunya in Spain. Their age ranged from 21 to 57 years (mean age: 45.7) and six were male. o All patients presented with fever (>37.7 C) and arthralgia. Four patients also had an itchy rash. Clinical and epidemiological features of the cases of chikungunya are presented in the Table.

Travel history

Nine cases resided in Catalonia and one in Cuenca,
Spain. However, all 10 had a history of recent travel to
Haiti and/or the Dominican Republic and for all symptoms had started either when abroad or within five days of their return to Spain.
Seven of the 10 cases had travelled to the Dominican
Republic, while two had been to Haiti. One case had visited both of these countries. The seven cases whose travel was limited to the Dominican Republic had done short trips there, which lasted less than a month.
These cases included two persons who were visiting friends and relatives (VFR) in very small village near
Santo Domingo and another person VFR who stayed in San Cristobal (south of the Dominican Republic).
The remaining four of the seven cases had travelled separately all over the Dominican Republic, one during a short period for work and three as tourists. The two cases who had only visited Haiti had been there as part of their job, as they worked for the same company.
During their stay, they lived together in the town of
Jacmel for eight months before returning to Spain. The case who had been both to Haiti and the Dominican
Republic was a tourist who had travelled there for a total period of four months.

www.eurosurveillance.org

Table
Clinical and epidemiological characteristics of cases of chikungunya in travellers returning from Haiti and/or the Dominican
Republic, Spain, April–June 2014
Cases

Sex

Approximate age in years

Country visited

Duration of stay (days)

Clinical symptomsa

Diagnosisb,c

Treatment required 1

M

In the 40s

Haiti

240

Fever, rash, arthralgia

PCR

NSAID

2

M

In the 50s

Haiti

240

Fever, rash , arthralgia

Serology

NSAID

3

F

In the 30s

Dominican Rep.

15

Fever, rash, arthralgia

PCR

Nothing

4

F

In the 50s

Dominican Rep.

15

Fever, arthralgia

PCR

NSAID

5

M

In the 50s

Dominican Rep.

15

Fever, headache, arthralgia

Serology

Nothing

6

M

In the 40s

Dominican Rep./Haiti

120

Fever, rash, arthralgia

Serology

NSAID

7

M

In the 40s

Dominican Rep.

5

Fever, weakness, polyarthralgia

Serology

Steroids

8

F

In the 50s

Dominican Rep.

7

Fever, arthralgia

PCR

NSAID

9

M

In the 40s

Dominican Rep.

24

Fever, headache, polyarthralgia

PCR

NSAID

10

F

In the 20s

Dominican Rep.

30

Fever, arthralgias

Serology

Nothing

Dominican Rep.: Dominican Republic; F: female; M: male; NSAID: Non-steroidal antinflammatory drug; PCR: polymerase chain reaction.
For all 10 cases, symptoms started either when abroad or within five days of their return to Spain.
Fever was defined as a temperature >37.7oC.
Diagnosis by PCR was done by a real-time reverse transcription-PCR (RT-PCR) (Realstar CHIKV kit, Altona diagnostics). c Diagnosis by serology included detection of both IgM and IgG against CHIKV in the first sample obtained, using a commercial immunofluorescence assay (Euroimmun). These cases were classified as probable cases. a b

Laboratory confirmation

For all cases, dengue virus infection was excluded through either polymerase chain reaction (PCR) or serological tests. In five of the 10 cases, chikungunya diagnosis was confirmed by real-time reverse transcription-PCR (RT-PCR) (Realstar CHIKV kit, Altona diagnostics). In the five remaining patients, chikungunya diagnosis was based both on IgM and IgG antibodies against CHIKV, which were detected by immunofluorescence (Euroimmun). PCR was not performed for such patients because the first diagnostic samples were obtained between 10 and 21 days after the onset of symptoms and the probability of viraemia was very low.

to four days [2] and clinical presentation has similarities with dengue fever. Chikungunya is characterised by fever, headache, rash and both acute and persistent arthralgia. Polyarthralgia is common in cases
CHIKV infection and is the most disabling symptom
[2]. Around 75% of infections are symptomatic [3] and general complications are rare but include myocarditis, hepatitis, ocular disorders, central nervous system involvement (encephalitis), and haemorrhagic fever [4].
Although the mortality rate associated with CHIKV is low, the arthralgia can persist or can recur for weeks or months [5] and the likelihood of developing persistent arthralgia is highly dependent on age, being more prevalent in those older than 45 years-old [2].

Treatment

Diagnosis

Although their condition significantly improved one or two weeks after symptom onset, the majority of cases required anti-inflammatory therapy. Three weeks after the onset of symptoms, only three patients were still taking anti-inflammatory drugs and one of them required steroids therapy during 15 days due to the persistence of polyarthralgia.

Background

CHIKV is an arbovirus of the genus Alphavirus transmitted by Aedes mosquitoes (mainly Ae. aegypti and
Ae. albopictus) [1].

The diagnosis should be based on clinical, epidemiological and laboratory criteria [2]. The laboratory confirmation is crucial to distinguish from other disorders with similar clinical manifestations, such as dengue fever, other diseases caused by alphaviruses, or malaria. In the acute phase of illness, detection of viral nucleic acid in serum by RT-PCR is possible [6]. After this period, diagnosis relies on detection of specific antibodies against CHIKV [7-8]. Laboratory confirmation of CHIKV infection is usually achieved by detection of viral genome or demonstration of seroconversion in paired serum samples [9].

Clinical manifestations of chikungunya

The disease caused by CHIKV has an incubation time that ranges from one to 12 days, with an average of two www.eurosurveillance.org 21

Geographical distribution of chikungunya virus Until 2005, CHIKV infection was endemic in some parts of east Africa and southeast Asia and cases were also reported from the Indian subcontinent [2,10].
Following outbreaks of chikungunya in islands of the
Indian Ocean and in peninsular India in 2005 [11], the virus also caused localised outbreaks in some countries in Europe, such as Italy (2007) and France (2010)
[12-13]. Before 2013, CHIKV infections had not been detected in the Americas but in December of that year, the first confirmed autochthonous case of CHIKV was reported in the Caribbean, in Saint Martin [14]. Since then, almost 800 confirmed cases of CHIKV infection have been reported from Saint Martin [15] and the virus has spread to the whole Caribbean. As of the end of
June 2014, almost 255,000 suspected cases have been reported from the Latin Caribbean and there are almost
180,000 suspected cases in the Dominican Republic

and Haiti, with 18 confirmed cases in the Dominican
Republic and 14 in Haiti [15-16].

Investigation of the chikungunya virus sequence derived from a case

A PCR targeting the partial envelope protein (E) 1 gene was done in addition to the real-time RT-PCR for one case (case 9), who had travelled to the Dominican
Republic [17]. Following amplification and sequencing of the gene, basic local alignment search tool
(BLAST) analysis revealed a 100% similarity index of the case’s sequence with sequences from strains recently identified in the British Virgin Islands (strain
99659; GenBank accession number: KJ451624) and
Saint Martin (strain CNR-20235/STMARTIN/2013, retrieved from the European virus archive (http://www. european-virus-archive.com)) [18]. Phylogenetic analysis, using MEGA5 software showed the strain affecting the patient to be of the Asian genotype, and in the

Figure
Phylogenetic analysis of a sequence derived from a case of chikungunya virus infection in a traveller returning from the
Dominican Republic to Spain, April 2014
CNR 20235 SAINT MARTIN _2013
KJ451624 BRITISH VIRGIN ISLANDS _2014
CNR 20236 SAINT MARTIN _2013

CARIBBEAN CLADE

308102 SPAIN ex DOMINICAN REPUBLIC_2014
FJ807897 TAIWAN ex INDONESIA_2007
EU192143_INDONESIA_2007
AB860301_PHILIPPINES_2013
KJ451623 3462 YAP STATE MICRONESIA 2013
INDONESIA 2010
FJ807889 TAIWAN ex INDONESIA_2008
GU969242 EAST TIMOR_2010
KF318729 CHINA ex SOUTHEAST ASIA _2012

ASIAN GENOTYPE

KC488650 CHINA ex SOUTHEAST ASIA _2012
KC879578 INDONESIA_2007
KJ451622 3807 YAP STATE MICRONESIA 2013
E806461 NEW CALEDONIA_2011
KF872195 RUSSIA ex INDONESIA_2013
FJ807888_TAIWAN ex INDONESIA_2008
KC879565 INDONESIA _2004
INDONESIA_2010
MALAYSIA 2006
FJ445483_SINGAPORE_2008
TAIWAN ex INDONESIA 2007-2008

EAST CENTRAL AFRICA GENOTYPE
WEST AFRICA GENOTYPE

0.005

The phylogenetic tree was constructed by neighbour-joining method and based on partial (450 nt) sequences of the chikungunya virus
Envelope protein 1 gene. The sequences analysed included one derived from the case reported here, which is highlighted (sequence
308102/2014), and 90 sequences retrieved from Genbank. Sequences from East and Central and West Africa were collapsed.

22

www.eurosurveillance.org

phylogenetic tree, the sequence derived from the case clustered together with other CHIKV sequences from the Caribbean (Figure). The sequence was deposited in
GenBank under accession number KM192348.

Discussion

We report 10 cases of chikungunya in Spain between
April and June 2014. Five of these can be considered as laboratory confirmed based on a positive specific real-time RT-PCR. The other five that tested positive for both IgM and IgG CHIKV antibodies can be classified as probable cases.
All cases had a clear epidemiological link to the
Dominican Republic and/or Haiti, two countries where they had recently travelled and which were concurrently affected by chikungunya. Symptom onset for all cases occurred either before returning to Spain or within a period compatible with infection abroad, based on the incubation time. Phylogenetic analysis of a viral sequence derived from one of the cases moreover showed 100% similarity with sequences from strains recently identified in the Caribbean.
After December 2013, when autochthonous transmission of CHIKV was first reported in Saint Martin, the virus spread within a few weeks to most countries of the Caribbean, where an outbreak is currently taking place [18]. A concomitant dengue outbreak in the region complicates differential diagnosis. Chikungunya presents a good example of the interaction between globalisation and emerging infections. During the last
10 years, the virus has spread throughout the Indian
Ocean, Asia, and localised outbreaks have also been reported in Europe [2]. Local transmission has been detected in the Americas in recent months. It is predicted that CHIKV will spread in most American areas where Aedes mosquitoes are endemic [14].
Cases of autochthonous transmission have not been reported in Spain but imported cases from countries affected by CHIKV have been documented in the past years [19,20] and a retrospective study reported 14 to 15 cases per year in the period between 2006 and
2007 [21]. Since April 2014 however, due to the situation in the Caribbean region, the numbers of cases have increased and in addition to the cases presented here further more recent cases have occurred (data not shown). According to last data from the World Tourism
Organization (data from 2008–2012), Spain is one of the
European countries with a largest number of travellers to Haiti and the Dominican Republic [22]. Moreover, the presence of immigrants in Europe from the Caribbean
[23, 24] may also account for trips to these countries.
The number of imported cases of CHIKV into Europe is likely to increase in the following weeks.
Aedes aegypti, one of the main vectors of CHIKV, is present in some areas of Europe, such as Madeira [25]. Ae. albopictus, the other vector, is already established in various countries in Europe, such as Italy, the south of www.eurosurveillance.org France and some regions in Spain [26, 27-29]. In Spain, the mosquito is found in most parts of Catalonia, the region where most of our cases (9/10) were residing, and in the Baleares islands as well as some territories of Murcia and Valencia [26]. Although Ae. Albopictus is currently not established in Cuenca, where one of the cases lived, this town is approximately 200 km away from Valencia.
The presence of a chikungunya vector together with travellers, who are still in the period of viraemia, as for five of our cases, could be a source of local transmission of CHIKV infection. In fact, an outbreak of autochthonous CHIKV infection already occurred in north-eastern Italy in 2007 after an index case arrived from India [30]. This led to an estimate of 254 locallyacquired infections [30]. With vectors established in parts of Europe and the intense circulation of people between this continent and America, there is a threat for new localised outbreaks of CHIKV infection in
Europe [18].
At this time, surveillance in the Catalonian region [31] where the vector is established is based on activecase finding. The surveillance is activated when either a confirmed case is detected or when a probable case in Catalonia could be viraemic. Moreover, primary healthcare centres belonging to the local area where the probable or confirmed case is detected are warned and, in parallel, the regional government in Catalonia is trying to activate measures to control the vector in the affected areas.
The set up of a surveillance system that can accurately identify chikungunya cases presents difficulties since the symptoms of the infection are not very specific.
However, although confusion between dengue and chikungunya is possible, in most cases the symptoms of chikungunya are specific enough to be recognisable in travellers by clinicians who are aware of the disease.

Conclusions

CHIKV infection might be suspected in any people returning from the Caribbean with fever, particularly if disabling arthralgias are present. In regions infested with Ae. albopictus or Ae. aegypti, health authorities should be aware of the risk of local outbreaks and the need to implement control measures for both vectors.

Acknowledgements
The CRESIB Research group receives funds from AGAUR,
(project 2009SGR385) and also from the project RICET
(RD12/0018/0010) within the Spanish National plan of R+D+I and co-funded by ISCIII-Subdireccion General de Evaluacion and the Fondo Europeo de Desarrollo Regional (FEDER).
CRESIB institution belongs to the TROPNET network. This work has been partially funded by the project PI10/00069FIS
(Fondo de Investigaciones Sanitarias)

23

Conflict of interest
None declared.

Authors’ contributions
AR, CG, EA, AC, JAV, AM, MR, IP and JA took clinical care of the patients, since admission to hospital and at outpatient clinic once discharged. MJM, LF and MPSS, performed the laboratory investigations and phylogenetic analysis of the virus, JG and JAPM were the senior supervisor of the article.
All authors participated in writing the manuscript.

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www.eurosurveillance.org

Rapid communications

Large number of imported chikungunya cases in mainland France, 2014: a challenge for surveillance and response M C Paty1, C Six2, F Charlet3, G Heuzé4 , A Cochet5, A Wiegandt6, J L Chappert7, D Dejour-Salamanca8, A Guinard9, P Soler10,
V Servas11, M Vivier-Darrigol12, M Ledrans13, M Debruyne14 , O Schaal15, C Jeannin16, B Helynck (b.helynck@invs.sante.fr)1, I
Leparc-Goffart17, B Coignard1
1. French Institute for Public Health Surveillance (Institut de Veille Sanitaire, InVS), Saint-Maurice, France
2. Regional office of the French Institute for Public Health Surveillance (Cire Sud), Marseille, France
3. Regional Health Agency (ARS) of Provence-Alpes-Côte d’Azur, Marseille, France
4. Regional Health Agency (ARS) of Corsica, Ajaccio, France
5. Regional office of the French Institute for Public Health Surveillance (Cire Languedoc Roussillon), Montpellier, France
6. Regional Health Agency (ARS) of Languedoc Roussillon, Montpellier, France
7. Regional office of the French Institute for Public Health Surveillance (Cire Rhône Alpes), Lyon, France
8. Regional Health Agency (ARS) of Rhône Alpes, Lyon, France
9. Regional office of the French Institute for Public Health Surveillance (Cire Midi Pyrénées), Toulouse, France
10. Regional Health Agency (ARS) of Midi Pyrénées, Toulouse, France
11. Regional office of the French Institute for Public Health Surveillance (Cire Aquitaine), Bordeaux, France
12. Regional Health Agency (ARS) of Aquitaine, Bordeaux, France
13. Regional office of the French Institute for Public Health Surveillance (Cire Antilles Guyane), Fort-de-France, France
14. Laboratoire Cerba, Saint-Ouen l’Aumône, France
15. Laboratoire Biomnis, Lyon, France
16. EID: Public mosquito control agency, Montpellier, France
17. Institut de Recherche Biomédicale des Armées, National Reference Laboratory for arboviruses, Marseille, France
Citation style for this article:
Paty MC, Six C, Charlet F, Heuzé G, Cochet A, Wiegandt A, Chappert JL, Dejour-Salamanca D, Guinard A, Soler P, Servas V, Vivier-Darrigol M, Ledrans M, Debruyne M,
Schaal O, Jeannin C, Helynck B, Leparc-Goffart I, Coignard B. Large number of imported chikungunya cases in mainland France, 2014: a challenge for surveillance and response. Euro Surveill. 2014;19(28):pii=20856. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20856
Article submitted on 08 July 2014 / published on 17 July 2014

During the summer of 2014, all the pre-requisites for autochthonous transmission of chikungunya virus are present in southern France: a competent vector, Aedes albopictus, and a large number of travellers returning from the French Caribbean islands where an outbreak is occurring. We describe the system implemented for the surveillance of chikungunya and dengue in mainland France. From 2 May to 4 July 2014, there were 126 laboratory-confirmed imported chikungunya cases in mainland France.
In November 2013, locally acquired cases of chikungunya were laboratory-confirmed in the French Caribbean island of Saint Martin [1]. The chikungunya virus rapidly spread in the surrounding French territories
(Martinique, Guadeloupe, Saint Barthélemy and French
Guiana) in December 2013 and then in most of the islands of the Caribbean [2,3]. By 15 June 2014, there were more than 80,000 clinically compatible cases in the French Caribbean Islands, based on the estimation of the sentinel surveillance [4]. Given the epidemic situation in the French Caribbean, and due to the large amount of travel between mainland France and the
Caribbean, it is expected that a large number of chikungunya cases will be imported to mainland France in
2014.

www.eurosurveillance.org

During the summer of 2014, all the pre-requisites for autochthonous transmission of chikungunya virus, and to a lesser extent, dengue virus, will then be present in southern France: a competent vector [5], a large number of viraemic travellers, and favourable climatic conditions for mosquito reproduction and viral replication in the mosquitoes. The likelihood of chikungunya transmission in mainland France is therefore particularly high.

Surveillance of chikungunya and dengue in mainland France

Chikungunya and dengue are mosquito-borne viral diseases, transmitted by Aedes mosquitoes, in particular Aedes aegypti and Aedes albopictus, the latter being present in Europe [6,7]. Since it was identified in 2004 in the French administrative district of AlpesMaritimes, Ae. albopictus has continued to spread in southern France [8,9].
Since 2006, in response to Ae. albopictus establishment in southern France, the French Ministry of Health has implemented a dengue and chikungunya preparedness and response plan to monitor and prevent the risk of dissemination of the two viruses in mainland France
[10]. Because the two diseases present a number of similarities regarding the clinical and entomological

25

Figure 1
Establishment of Aedes albopictus, by administrative district and year, mainland France, 2004–2014

Year of establishment

No establishment
2004
2006
2007
2009
201 0
2011
201 2
201 3
201 4

±

0

75

150 km Source: IGN-GéoFLA, 1999: French Institute for Public Health Surveillance (Institut de Veille Sanitaire, InVS), 2014.

features, a common system has been set up comprising entomological and epidemiological surveillance.

Entomological surveillance for chikungunya and dengue

The entomological surveillance is operated by public local structures of mosquito control, under the coordination and responsibility of the Ministry of Health.
The presence and the spread of Ae. albopictus is monitored using ovitraps placed along the French
Mediterranean coastline and land inwards along
26

motorways. Traps are checked at least monthly for presence of Ae. albopictus eggs. Mosquitoes and eggs are not tested routinely for the presence of dengue and chikungunya viruses.
The administrative districts, according to the year of establishment of Ae. albopictus, are shown in Figure 1: from one district in 2004, Ae. albopictus has become established in 18 administrative districts in six regions
(Provence-Alpes-Côte d’Azur, Corsica, LanguedocRoussillon, Rhône-Alpes, Aquitaine, Midi-Pyrénées) in
2014.
www.eurosurveillance.org

Epidemiological surveillance for chikungunya and dengue

From May to November, when the vector is active, all suspected imported cases must be immediately reported to the regional health authorities
(Agences Régionales de Santé, ARS). Appropriate vector control measures are then implemented within 200 metres of the places visited by the patients during the likely viraemic period (from the day before until seven days after the onset of symptoms [11]), without waiting for laboratory confirmation of the infection;
• daily reporting from a network of laboratories of the results of chikungunya and dengue serological or RT-PCR tests to the French Institute of
Public Health Surveillance (Institut de veille sanitaire, InVS). This catches cases who have not been reported through the notification system and the seasonal enhanced surveillance, and thus serves to improve the completeness of reporting of the surveillance system.

A suspected case is defined as a person with acute fever (>38.5 °C) and joint pains (chikungunya) or at least one of the following symptoms: headache, retro-orbital pain, joint pains, myalgia or lower back-pain (dengue), not explained by another medical condition. For both diseases, cases are confirmed by serology (IgM positive or a fourfold increase in IgG titre) or detection of viral nucleic acids in plasma by real-time reverse transcription polymerase chain reaction (RT-PCR), or for dengue, a positive dengue nonstructural protein 1
(NS1) antigenic test.
The surveillance system aims to prevent or to contain autochthonous transmission of dengue and chikungunya, and comprises three components:
• nationwide year-long mandatory notification of laboratory-confirmed cases of chikungunya and dengue; • seasonal enhanced surveillance in the administrative districts where the vector is established.

The notification of a laboratory-confirmed locally acquired case triggers immediate epidemiological and entomological investigations, in order to assess the

Figure 2
Laboratory-confirmed imported chikungunya cases in mainland Francea, laboratory-confirmed imported chikungunya cases in Aedes albopictus-established districts in mainland France during the period of vector activityb and estimated number of clinically compatible chikungunya cases in the French Caribbeanc
12,000

120

Es ti mated number of chikungunya ca s es i n French Ca ribbean

10,000

Number of confirmed imported chikungunya cases in mainland France (n=475)

100

Number of confirmed imported chikungunya cases in
Aedes albopictus-infested districts of mainland France
(n=126)
8,000

90

Estimated number of chikungunya cases in French
Caribbean (n=99,870)

80
70

6,000

60
50

4,000

40
30

2,000

20
10

0

45 46 47 48 49 50 51

52

2013

1

2

2014

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18 19 20 21 22 23 24 25 26 27

Number of confirmed imported chi kungunya cases in mainland Fra nce

110

0

Week number

Per week, week 45 2013 to week 26 2014 (1 November 2013 to 27 June 2014), source: laboratory network. Data for week 26 2014 are not yet consolidated and are not available for week 27 2014. b Per week, weeks 18 to 27 2014 (2 May to 4 July 4 2014), source: enhanced surveillance. c Per week, week 48 2013 to week 26 2014 (25 November 2013 to 29 June 2014). Data are not available for week 27 2014, source: French
Caribbean sentinel surveillance. a www.eurosurveillance.org

27

Table 1
Suspected and laboratory-confirmed cases of chikungunya and dengue, by region involved in seasonal enhanced surveillance, mainland France, 2 May–4 July (weeks 18 to 27) 2014

Regions

Provence-Alpes-Côte d'Azur

Number of administrative districts where Aedes albopictus is established Resident population in administrative districts where the vector is establisheda Number of suspected cases

5

4,777,464

121

Number of laboratory-confirmed imported cases

Number of laboratory-confirmed autochthonous cases

Chikungunya

Dengue

Chikungunya

Dengue

43

17

0

0

Corsica

2

314,486

4

0

0

0

0

Languedoc-Roussillon

4

2,592,890

55

28

6

0

0

Rhône-Alpes

4

3,764,718

76

27

12

0

0

Aquitaine

2

1,794,528

31

14

5

0

0

Midi-Pyrénées
Total
a

1

1,260,226

63

14

7

0

0

18

14,504,312

350

126

47

0

0

Source: French national institute of economic and statistical information (Institut national de la statistique et des études économiques,
INSEE

autochthonous transmission and to guide vector control measures. The investigation and control measures include: (i) active case finding in the neighbourhood of the case’s residence and in other areas visited by the case; (ii) recommending personal protection measures for the viraemic patient; (iii) encouraging health professionals to screen suspected cases; (iv) carrying out perifocal vector control activities, within 200 metres of the case’s residence, including destruction of mosquito breeding sites and spraying targeted at adult mosquitoes; (v) giving information to the public about personal protection and reduction of mosquito breeding sites.

Chikungunya cases in mainland France

Throughout mainland France, 475 laboratory-confirmed imported cases of chikungunya were notified through the laboratory network from 1 November 2013
(the month of confirmation of the first cases in Saint
Martin) to 27 June 2014 (Figure 2), whereas during the whole of 2011 and 2012, there were 33 and 17 cases, respectively. From 2 May to 4 July 2014, of 350 suspected cases who were notified to the regional health authorities, 126 were laboratory-confirmed imported cases of chikungunya and 47 laboratory-confirmed imported cases of dengue were detected in the Ae. albopictus-established districts (Table 1 and Figure 2). A large majority of the laboratory-confirmed imported cases of chikungunya arrived from the French Caribbean (85% (107/126), as shown in Table 2). More than 80% of cases (n=103) were in an Ae. albopictus-established district while potentially viraemic (the remaining 20% were diagnosed retrospectively). No autochthonous case has been confirmed to date. More information and updated surveillance results are provided on the InVS website
[4].

28

Discussion

From 2006 to 2013, the number of laboratory-confirmed imported cases of chikungunya reported in Ae. albopictus-established districts from May to November ranged from 2 to 6 [4]. From 2 May to 4 July 2014, the number of laboratory-confirmed imported cases of chikungunya was much higher (126) than in previous years, as a consequence of the chikungunya outbreak in the Caribbean region.
Although no autochthonous case has been confirmed to date in 2014, the conditions required for autochthonous transmission of the chikungunya virus are met: the population in mainland France is immunologically naive to the virus; a competent vector exists, Ae. albopictus [5] and its distribution has been constantly and rapidly spreading for the past 10 years [10]; and the probability of introduction of the virus by travellers coming from affected areas is high. The possibility of occurrence of autochthonous transmission of arboviruses has been demonstrated in the recent past in southern France, with the identification of two autochthonous dengue cases in 2010 and one in 2013, as well as two autochthonous chikungunya cases in 2010
[12-14].
Passenger traffic between mainland France and
Martinique and Guadeloupe is high, with more than 2.5 million plane passengers in 2013 [15]. During this summer of 2014 – when the mosquito is active – large numbers of travellers will return from the French Caribbean islands where an outbreak is currently occurring.
Among them, a high proportion will possibly be viraemic upon their arrival, increasing the probability of the occurrence of autochthonous cases of chikungunya in the administrative districts where Ae. albopictus is established, and increasing the risk of a chikungunya outbreak in mainland France.

www.eurosurveillance.org

Table 2
Laboratory-confirmed chikungunya cases imported to mainland France, by place of origin, as of 4 July (week 27)
2014
Place of origin

Number of cases imported to mainland France

investigations. Monique Debruyne, Oriane Schaal and
Isabelle Leparc-Goffart are in charge of virological analysis and transmit the results on a daily basis to the surveillance teams. Charles Jeannin is an entomologist in charge of entomological investigations and mosquito control activities.
Bruno Coignard reviewed the final document for accuracy.
All authors contributed to the review of the manuscript and approved the final version.

Guadeloupe

70

Martinique

36

Haiti

10

References

Dominican Republic

3

Tonga

1

Sierra Leone

1

Saint Martin

1

Indonesia

1

Côte d’Ivoire

1

Costa Rica

1

Cambodia

1

1. Cassadou S, Boucau S, Petit-Sinturel M,Huc P,LeparcGoffart I,Ledrans M. Emergence of chikungunya fever on the French side of Saint Martin island, October to December
2013 6. Euro Surveill. 2014;19(13):pii=20752. http://dx.doi. org/10.2807/1560-7917.ES2014.19.13.20752 2. Van Bortel W, Dorleans F, Rosine J, Blateau A, Rousset D,
Matheus S, et al. Chikungunya outbreak in the Caribbean region, December 2013 to March 2014, and the significance for
Europe. Euro Surveill. 2014;19(13):pii=20759. http://dx.doi. org/10.2807/1560-7917.ES2014.19.13.20759 3. Ledrans M, Cassadou S, Boucau S, Huc-Anaïs P, LeparcGoffart I, Prat C, et al. Émergence du chikungunya dans les départements français d’Amérique: organisation et résultats de la surveillance épidémiologique, avril 2014. [Emergence of chikungunya in the French overseas territories of the Americas: organization and results of epidemiological surveillance,
April 2014]. Bull Epidémiol Hebd (Paris). 2014;(21-22):368-79.
French. Available from: http://www.invs.sante.fr/beh/2014/2122/2014_21-22_1.html
4. French Institute for Public Health Surveillance (Institut de
Veille Sanitaire, InVS). Chikungunya. [Chikungunya]. Paris:
InVS. [Accessed 16 Jul 2014]. French. Available from: http:// www.invs.sante.fr/%20fr/Dossiers-thematiques/Maladiesinfectieuses/Maladies-a-declaration-obligatoire/Chikungunya/ Donnees-epidemiologiques
5. Vega-Rua A, Zouache K, Caro V, Diancourt L, Delaunay P,
Grandadam M, et al. High efficiency of temperate Aedes albopictus to transmit chikungunya and dengue viruses in the Southeast of France. PLoS One. 2013;8(3):e59716. http:// dx.doi.org/10.1371/journal.pone.0059716 6. Schaffner F, Medlock JM, Van Bortel W. Public health significance of invasive mosquitoes in Europe. Clin
Microbiol Infect. 2013;19(8):685-92. http://dx.doi. org/10.1111/1469-0691.12189 7. Queyriaux B, Armengaud A, Jeannin C, Couturier E, PelouxPetiot F. Chikungunya in Europe. Lancet. 2008;371(9614):7234. http://dx.doi.org/10.1016/S0140-6736(08)60337-2
8. European Centre for Disease Prevention and Control (ECDC).
Mosquito maps. Stockholm: ECDC. [Accessed 16 Jul 2014].
Available from: http://ecdc.europa.eu/en/healthtopics/ vectors/vector-maps/Pages/VBORNET_maps.aspx 9. European Centre for Disease Prevention and Control (ECDC).
Aedes albopictus factsheet. Stockholm: ECDC [Accessed 16
Jul 2014]. Available from: http://www.ecdc.europa.eu/en/ healthtopics/vectors/mosquitoes/Pages/aedes-albopictusfactsheet.aspx 10. Ministère des Affaires Sociales et de la Santé. Guide relatif aux modalités de mise en oeuvre du plan anti-dissémination du chikungunya et de la dengue en métropole. [Dengue and chikungunya preparedness and response plan to monitor and prevent the risk of dissemination in mainland France]. Paris :
Ministère des Affaires Sociales et de la Santé; 2014. French.
[Accessed 16 July 2014]. Available from: http://circulaire. legifrance.gouv.fr/pdf/2014/05/cir_38279.pdf 11. Leo YS, Chow AL, Tan LK, Lye DC, Lin L, Ng LC. Chikungunya outbreak, Singapore, 2008. Emerg Infect Dis. 2009;15(5):836-7. http://dx.doi.org/10.3201/eid1505.081390 12. La Ruche G, Souarès Y, Armengaud A, Peloux-Petiot F,
Delaunay P, Desprès P, et al. First two autochthonous dengue virus infections in metropolitan France, September 2010. Euro
Surveill. 2010;15(39):pii=:19676.
13. Marchand E, Prat C, Jeannin C, Lafont E, Bergmann T, Flusin O, et al. Autochtonous case of dengue in France, October 2013.
Euro Surveill. 201;18(50):pii=20661.
14. Grandadam M, Caro V, Plumet S, Thiberge JM, Souarès Y,
Failloux AB, et al. Chikungunya virus, southeastern France.
Emerg Infect Dis. 2011 May;17(5):910-3. http://dx.doi. org/10.3201/eid1705.101873 15. Direction du Transport aérien. Bulletin statistique trafic aérien commercial - année 2013. [Statistical Bulletin - Commercial air traffic - 2013]. Paris: Ministère de l’écologie, du développement durable et de l’énergie; 2014. [Accessed 7 Jul 2014]. French.
Available from: http://www.developpement-durable.gouv.fr/
IMG/pdf/Bulletin_Stat_2013_20140527.pdf

Total

126

Source: seasonal enhanced surveillance system, mainland France.

The preparedness and response plan developed in mainland France since 2006 has proved to be effective for the early detection of cases and implementation of vector control measures to prevent or contain autochthonous transmission of dengue and chikungunya viruses. However, it is currently challenged by the increased number of imported chikungunya cases. It is thus crucial to maintain a high level of mobilisation of all actors within the surveillance system. They are also an important source of information for the general population, to encourage the use of personal protection against mosquito bites and control of mosquito breeding sites.
The challenge that we face is to avoid the establishment of a local cycle of transmission in mainland France and, beyond, in other European areas where competent vectors are also present.
Acknowledgements
We would like to thank the personnel of diagnostic laboratories and the clinicians involved in the surveillance system.

Conflict of interest
None declared.

Authors’ contributions
Marie-Claire Paty coordinates the chikungunya and dengue surveillance system at the national level. Brigitte Helynck and Marie-Claire Paty co-drafted the manuscript. Caroline
Six, Francis Charlet, Guillaume Heuzé, Amandine Cochet,
Axel Wiegandt, Jean Loup Chappert, Dominique DejourSalamanca, Anne Guinard, Pauline Soler, Véronique Servas,
Martine Vivier-Darrigol, Martine Ledrans are responsible at regional level for the surveillance and epidemiological www.eurosurveillance.org 29

Euroroundups

Chikungunya outbreak in the Caribbean region,
December 2013 to March 2014, and the significance for
Europe
W Van Bortel (wim.vanbortel@ecdc.europa.eu)1, F Dorleans2, J Rosine2, A Blateau2, D Rousset3, S Matheus3, I Leparc-Goffart 4 ,
O Flusin4 , C M Prat 4 , R Césaire5, F Najioullah5, V Ardillon6, E Balleydier 7, L Carvalho6, A Lemaître8, H Noël8, V Servas9, C Six10, M
Zurbaran8, L Léon8, A Guinard 11, J van den Kerkhof12, M Henry13, E Fanoy12,14,15, M Braks12, J Reimerink12, C Swaan12, R Georges16, L
Brooks17, J Freedman18, B Sudre1, H Zeller1
1. European Centre for Disease Prevention and Control, Stockholm, Sweden
2. French Institute for Public Health Surveillance, Fort-de-France, Martinique
3. National Reference Centre, Institut Pasteur de la Guyane, Cayenne, French Guiana
4. National Reference Centre, IRBA, Marseille, France
5. University Hospital Laboratory of virology, Fort-de-France, Martinique
6. French Institute for Public Health Surveillance, Cayenne, French Guiana
7. French Institute for Public Health Surveillance, Saint-Denis, La Réunion
8. French Institute for Public Health Surveillance, Paris, France
9. French Institute for Public Health Surveillance, Bordeaux, France
10. French Institute for Public Health Surveillance, Marseille, France
11. French Institute for Public Health Surveillance, Toulouse, France
12. National Institute for Public Health and the Environment, Bilthoven, The Netherlands
13. Section General Public Health of the Department of Collective Prevention Services, Sint Maarten
14. European Programme for Intervention and Epidemiology Training, Stockholm, Sweden
15. Public Health Service Region of Utrecht, Zeist, the Netherlands
16. Ministry of Health and Social Development, British Virgin Islands
17. Ministry of Social Development, Government of Anguilla
18. Public Health England, United Kingdom
Citation style for this article:
Van Bortel W, Dorleans F, Rosine J, Blateau A, Rousseau D, Matheus S, Leparc-Goffart I, Flusin O, Prat CM, Césaire R, Najioullah F, Ardillon V, Balleydier E, Carvalho
L, Lemaître A, Noël H, Servas V, Six C, Zurbaran M, Léon L, Guinard A, van den Kerkhof J, Henry M, Fanoy E, Braks M, Reimerink J, Swaan C, Georges R, Brooks
L, Freedman J, Sudre B, Zeller H. Chikungunya outbreak in the Caribbean region, December 2013 to March 2014, and the significance for Europe. Euro Surveill.
2014;19(13):pii=20759. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20759
Article submitted on 01 March 2014 / published on 3 April 2014

On 6 December 2013, two laboratory-confirmed cases of chikungunya without a travel history were reported on the French part of the Caribbean island of Saint
Martin, indicating the start of the first documented outbreak of chikungunya in the Americas. Since this report, the virus spread to several Caribbean islands and French Guiana, and between 6 December 2013 and
27 March 2014 more than 17,000 suspected and confirmed cases have been reported. Further spread and establishment of the disease in the Americas is likely, given the high number of people travelling between the affected and non-affected areas and the widespread occurrence of efficient vectors. Also, the likelihood of the introduction of the virus into Europe from the Americas and subsequent transmission should be considered especially in the context of the next mosquito season in Europe. Clinicians should be aware that, besides dengue, chikungunya should be carefully considered among travellers currently returning from the Caribbean region.

Introduction

Chikungunya is a mosquito-borne viral disease caused by an alphavirus from the Togaviridae family. The virus is transmitted by the bite of Aedes mosquitoes, primarily Aedes aegypti and Aedes albopictus. The
30

typical clinical signs of the disease are fever and severe arthralgia, which may persist for weeks, months or years after the acute phase of the infection [1]. General complications include myocarditis, hepatitis, ocular and neurological disorders [2]. The detection and diagnosis of the disease can be challenging especially in settings where dengue is endemic. It was estimated that three to 25% of infected individuals are asymptomatic. Blood-borne transmission is possible [3,4] and mother-to-child transmission has also been reported in newborns of viraemic women who developed the disease within the week prior to delivery [5,6].
Chikungunya has been, up to 2005, found to be endemic in parts of Africa, south-east Asia and on the Indian subcontinent (see historical overview: Figure 1). Prior to 2005, outbreaks occurred mainly in the well-known endemic areas. From 2005 to 2006, large chikungunya outbreaks were reported from Comoros, Mauritius,
Mayotte, Réunion and various Indian states (Figure 1).
In 2013, chikungunya outbreaks occurred in a variety of geographic locations within India (Gujarat, Tamil
Nadu, Kerala, Odisha states), Indonesia (East Jakarta,
East Java), Micronesia (Yap), the Philippines archipelago, including the city of Manila, as well as Singapore, and the first evidence of autochthonous transmission www.eurosurveillance.org Figure 1
Historical overview of the chikungunya outbreaks prior to the emergence of the chikungunya virus in the Caribbean in
December 2013

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The Figure is based on references [29-81]. The detection of the chikungunya virus in the Caribbean in December 2013 constitutes the first finding of the virus in the Americas, therefore this region of the world is not shown on the map. Each square represents a particular period: the left square represents period 1950–1979, the middle square period 1980–2004 and the right square period 2005–October 2013.
The squares are coloured yellow, orange and red respectively when an outbreak was reported in the literature. Otherwise the square is white-crossed. in New Caledonia and Papua New Guinea was reported in June 2012 (Figure 1 and [7]). Autochthonous transmission in continental Europe was first reported from
Emilia-Romagna, Italy, in August 2007 with more than
200 confirmed cases [8] and subsequently in 2010 in the Var, France with two confirmed cases [9]. In both areas the vector Ae. albopictus is established [10].
Three different genotypes of chikungunya virus, namely Asian, West African, and East/Central/South
African (ECSA), have been identified. The acquisition of an A226V mutation in the envelope protein E1 of
ECSA chikungunya virus, as observed in Réunion in
2005, increased the transmissibility of the virus by the widely distributed Ae. albopictus mosquitoes [11]. This mutated virus spread from the Indian Ocean to East
Africa and Asia and was involved in the chikungunya outbreak in Italy [8]. Phylogenetic analysis proved that the chikungunya virus responsible for autochthonous cases in France belonged to the ECSA strain, but without the mutation at position 226 [9].

www.eurosurveillance.org

On 6 December 2013, two laboratory-confirmed cases of chikungunya without a travel history were reported on the French part of the Caribbean island of Saint
Martin in the context of a dengue outbreak occurring on this island [12] and the virus spread since then to other islands in the Caribbean. This is the first documented outbreak of chikungunya with autochthonous transmission in the Americas. This paper aims to review the current epidemiological situation of chikungunya in the
Caribbean region, to assess its significance for both the region and the European Union (EU) and to provide an historical overview of the geographical emergence of chikungunya.

Epidemiology of chikungunya in the
Caribbean
The Caribbean French overseas territories:
French Guiana, Guadeloupe, Martinique, Saint
Barthélemy and Saint Martin

The Caribbean French overseas territories include the islands Guadeloupe, Martinique, Saint Barthélemy
31

Figure 2
Number of confirmed and estimated suspected chikungunya cases reported in the Caribbean by week of sampling,
1 December 2013–23 March 2014
180

Guadeloupe (confirmed)

160

Sint Maarten (confirmed)

1,800

British Virgin Islands - Jost Van Dyke (confirmed)
1,600

Number of confirmed cases (bars)

140

1,400

Saint Barthélemy (suspected)
Guadeloupe (suspected)

120

1,200

Saint Martin (suspected)
Martinique (suspected)

100

1,000

80

800

60

600

40

400

20

Number of estimated clinical suspected cases

Anguilla (confirmed)

200

0

0

Year-week
The period 1 December 2013–23 March 2014 corresponds to week 48 2013–week 12 2014. From week 5 2014 onwards the expert committee for emerging and infectious diseases of Martinique, Saint Barthélemy and Saint Martin recommended to focus the laboratory diagnostics on patients for which laboratory confirmation is needed to support case management. From then, the systematic confirmation of cases was ceased on these islands. Therefore the confirmed cases (bars) are only shown for Anguilla, Guadeloupe, Jost Van Dyke and Sint Maarten.
Estimated numbers of suspected clinical cases (lines) are respectively provided for Guadeloupe, Martinique, Saint Barthélemy, and Saint
Martin.

and Saint Martin, and French Guiana on the South
American continent. Dengue surveillance and control are well established on the Caribbean French overseas territories. In mid-November 2013, the suspicion of autochthonous transmission of chikungunya virus on the island of Saint Martin was brought to the attention of the local health authorities. On 6 December 2013, a first suspected case of chikungunya occurring in the French part of the island was laboratory confirmed and an outbreak phase was declared the same day for Saint
Martin.
Following this confirmation, enhanced surveillance for chikungunya cases was implemented not only in Saint
Martin but also in the other Caribbean French overseas territories, because intense travel of people occurs between the affected island and these neighbouring territories. Based on the phase of the outbreak in the different territories – each territory declares the outbreak-phase based on their assessment/context – the following components of the surveillance system were either implemented or strengthened to achieve the early detection of suspected chikungunya cases
32

and to monitor the evolution of the epidemic. (i) During the pre-outbreak phase, i.e. when the first autochthonous cases are detected and laboratory confirmed, the surveillance focussed on systematic confirmation of cases. Therefore, general practitioners and medical microbiologists were invited to report all clinical suspected cases of chikungunya using a specific notification form. A clinical suspected case was defined as any individual with sudden onset of fever (>38.5°C) with arthralgia and without any other aetiology. Laboratory investigations were systematically conducted on all clinical suspected cases. A confirmed case was defined as a clinical suspected case with laboratory confirmation, either a positive reverse transcription-polymerase chain reaction (RT-PCR) or a positive detection of IgM and IgG or both; (ii) once the outbreak was declared by the local authorities, i.e. the outbreak phase, the surveillance was performed through the weekly notification of clinical suspected cases by the sentinel network of general practitioners; in Saint Martin, all general practitioners and one paediatrician were asked to report the number of clinical suspected cases. Further all hospitals in the territories had to weekly notify emergency room visits for suspected cases, and hospital admissions for confirmed cases. The systematic www.eurosurveillance.org Figure 3
Local chikungunya transmission and imported cases in the islands of the Caribbean region and in French Guiana, 1 December
2013–23 February 2014
70°0'0"W

60°0'0"W

Haiti
Dominican Republic

North Atlantic Ocean

British Virgin Islands
Anguilla

Puerto Rico

Saint Martin & Sint Maarten
Saint Barthélemy
Virgin Islands

Saint Kitts and Nevis
Antigua and Barbuda
Montserrat
Guadeloupe

Dominica

Martinique

Caribbean Sea
Saint Lucia
Saint Vincent and the Grenadines
Barbados
Bonaire, Saint Eustatius and Saba

Aruba

Curaçao

Grenada

as

10°0'0"N

Trinidad and Tobago

0

62.5

125

250

375

500 Kilometers

Venezuela bs Imported case

²

Current transmission

The period 1 December 2013–23 February 2014 corresponds to week 48 2013–week 8 2014.

laboratory confirmation of all suspected cases was ceased in week 5 2014 in Martinique, Saint Barthélemy and Saint Martin to prevent overloading the laboratories performing the diagnosis.
Strengthened surveillance enabled the detection of confirmed cases of chikungunya on French territories other than Saint Martin. Data were collected at the local level and regional level (i.e. the Regional Office of the French Institute for Public Health Surveillance,
Fort-de-France, Martinique) in order to follow the progression of the virus in the different territories (French
Guiana, Guadeloupe, Martinique, Saint Barthélemy,
Saint Martin), to coordinate the activities and to harmonise common tools (questionnaires, templates, protocols) used during the pre-outbreak and outbreak management phases.
Epidemiological situation
Since the introduction of the chikungunya virus in
Saint Martin and subsequent implementation of www.eurosurveillance.org enhanced surveillance, the first cases in Martinique,
Guadeloupe, Saint Barthélemy and French Guiana were confirmed on 18, 24, 30 December 2013 and 19
February 2014 respectively. Since the start of the outbreak the number of suspected and confirmed cases increased indicating continuous transmission of the virus in all affected territories (Figure 2).
As of 27 March 2014, the estimated number of clinical suspected cases of chikungunya in Saint Martin was 2,750 and the number of confirmed cases was
784 (week 48 2013 to 12 2014).Three deaths indirectly related to chikungunya were reported.
A total of 435 clinical suspected cases were estimated on the island of Saint Barthélemy and 134 infections have been confirmed (week 50 2013 to 12 2014).
In Martinique, 9,340 clinical suspected cases of chikungunya were estimated (week 49 2013 to 12 2014) and
1,207 cases were identified as laboratory-confirmed
33

Figure 4
Weekly incidence of the estimated suspected cases of chikungunya by the sentinel network in Guadeloupe, Martinique, Saint
Barthélemy and Saint Martin, 1 December 2013–26 January 2014
90

Martinique
80

Guadeloupe
Saint-Martin

70

Saint-Barthélemy

Incidence (cases/10,000)

60

50

40

30

20

10

0

2013-48

2013-49

2013-50

2013-51

2013-52

2014-01

2014-02

2014-03

2014-04

Year -week

The period 1 December 2013–26 January 2014 corresponds to the weeks 48 2013–4 2014.

cases. Two deaths were reported in Martinique in hospitalised patients: one death was classified as indirectly linked with chikungunya; the second death is under investigation.
In Guadeloupe, a total of 2,270 clinical suspected cases were estimated to have occurred (week 52 2013 to 12 2014) and 734 cases were confirmed for the infection in this island (Figures 2 and 3).
A rapid increase of the weekly incidence was observed in the smaller islands Saint Martin (population: 36,029) and Saint Barthélemy (population: 9,035) compared to the larger islands Martinique (population: 392,290) and Guadeloupe (population: 404,640) (Figure 4).
Since the beginning of the outbreak, 11 cases from
Saint Martin and Martinique were imported in French
Guiana. The first autochthonous cases in French Guiana were reported on 19 February, with a total of 24 autochthonous laboratory-confirmed cases in week 11 2014.
In Saint Martin, all areas of the island have been affected by the virus, a predominant number of confirmed cases occurred in Sandy Ground, Concordia and
34

Quartier d’Orléans. In Martinique, the outbreak is geographically generalised. The main city, Fort-de-France, had the highest attack rate (estimated from the weekly number of notifications of clinical suspected cases) followed by, La Trinité, Case Pilote, Schoelcher, SaintPierre, and Les Anses d’Arlet. The main cluster identified in Guadeloupe was located in Baie-Mahault and in other municipalities of the windward shore of Basse
Terre. In total, 27 of 32 municipalities had at least one confirmed case.
Microbiological investigation
Before the outbreak phase, laboratory confirmation was requested for every clinical suspected case of chikungunya. The diagnostic algorithm was intended to be followed by practitioners and microbiological laboratories. The samples were processed according to the date of the onset of symptoms and the date of sample collection. When the sample was taken between the first and fifth day after symptom onset, the sample was processed by RT-PCR. When the sample was taken between the fifth and the seventh day after symptoms onset, the sample was processed both by RT-PCR and detection of IgM and IgG, for the remainder only IgM and IgG detection was performed. www.eurosurveillance.org Because both dengue and chikungunya viruses are currently circulating, dengue diagnostic was systematically performed parallel to chikungunya laboratory tests. The microbiological analysis strategy was adapted according to the respective outbreak situation. In the territories where there was evidence of wide virus spread, only at-risk patients (when laboratory confirmation was needed to support the case management) and uncommon forms of the infection were targeted for laboratory confirmation (Martinique, Saint
Barthélemy and Saint Martin, from week 5 2014). Local, regional and national capacities support the diagnostic strategy of the region (National Reference Laboratories and hospital-based microbiological laboratories).
On 10 December 2013, five days after the detection of the first autochthonous cases in Saint Martin, the complete chikungunya virus sequence showed that this virus belongs to the Asian genotype and the information was shared with the relevant public health authorities [13].
Control measures
All houses and work places of confirmed cases were targeted by vector control measures as scheduled in the Management, Surveillance and Alert of chikungunya outbreak Programme, which was implemented as a result of the outbreak. Epidemiological and entomological investigations were conducted simultaneously in the neighbouring environment of the suspected and confirmed cases (during pre-outbreak and outbreak phases) as well as interventions on the whole territory
(outbreak phase), to identify possible clusters of cases and to implement vector control targeting adult mosquitoes and their breeding sites.
Public education was established through radio spots, television, distribution of flyers and posters with prevention messages in public areas, airports, private practitioner’s offices, hospitals and clinics. The health authorities also implemented a specific programme preventing possible shortage of healthcare capacities due to the high burden of patients on emergency, hospital and outpatient capacities.

Overseas territories of the Netherlands

The overseas territories of the Netherlands in the
Caribbean region comprise six islands grouped in three smaller Windward Islands in the north, and three larger Leeward Islands in the south, just north of the Venezuelan coast. The total population of these islands is 320,000 and ranges from 2,000 (Saba) to over 147,000 (Curaçao). The three islands with a larger population, Aruba, Curaçao, and Sint Maarten, are independent states within the Netherlands, the other three islands (Bonaire, Sint Eustatius and Saba), the so-called BES islands, have the status of special municipalities within the Netherlands. Sint Maarten (close to
40,000 inhabitants) is the southern part of the island of which the Northern part is formed by Saint Martin. www.eurosurveillance.org Epidemiological situation
The first report of laboratory-confirmed autochthonous chikungunya case in the overseas territories of the
Netherlands was received by section General Public
Health of the Department of Collective Prevention
Services in Sint Maarten on 22 December 2013. The case had had onset of illness on 6 December 2013.
Since the start of the outbreak, the total number of confirmed patients diagnosed with chikungunya on Sint Maarten has been 234 (up to week 11 2014), including one hospitalised case. The Dutch case definition for confirmed cases is fever (>38.5°C) and joint pain in a person who has a positive polymerase chain reaction (PCR) and/or specific positive IgM antibody test. The proportion of test-positive samples increased from 29% (2/7) in December 2013 up to 69% (77/111) at the end of March 2014. The Caribbean Public Health
Association (CARPHA) is, amongst other activities, assisting the countries and territories in the Caribbean region in the surveillance of communicable diseases.
In this context they operate a syndromic surveillance system. Data from the surveillance showed for Sint
Maarten an average and stable number of patients with undifferentiated fever since December 2013. Since the end of January 2014, start of week 5, the syndromic surveillance showed a consistently higher number of cases of undifferentiated fever compared to the historical average, generally below five cases per week based upon four years of data. Since week 5, cases vary between two and 34 per week (an average of 13 per week between week 5 and 12). Although there has been an ongoing dengue outbreak during this period, the increase is likely to be due to chikungunya, given that dengue season started well before January.
The number of confirmed cases on Sint Maarten
(n=234) is much lower than on Saint Martin (n= 784) although the number of inhabitants of both parts of the island is comparable (ca. 40,000). Because of intense traffic occurs between the two parts of the island and ecological barriers are absent, there is no obvious reason why the disease would be more prominent in the northern than in the southern part of this small island
(87 km2). More likely, the difference in the number of reported cases is due to the difference in the availability of diagnostic testing and under-reporting. Twelve patients from Sint Maarten were diagnosed by general practitioners from Saint Martin. From the epidemiological data currently available, the residencies of most patients cannot be identified in a reliable manner.
The other two Dutch Windward islands, Saba and Sint
Eustatius, have small populations (2,000 and 3,900) of which no patients have been diagnosed so far. The syndromic surveillance on these islands shows a low and stable number of patients with undifferentiated fever since December 2013. A rise in these figures could be an early signal for emergence of chikungunya. In the
Dutch Leeward Islands, Aruba, Bonaire and Curaçao, no autochthonous cases have been identified so far.
One imported confirmed case returning from Saint
35

Martin was reported on the island of Aruba in the first week of February 2014 (Figures 2 and 3).

53,200 (Cayman Islands). All are internally self-governing UK overseas territories.

Microbiological investigation
The first three patients from Sint Maarten were diagnosed by the French National reference laboratory (CNRIRBA Marseille) using RT-PCR testing. On January 2014, serum samples from Sint Maarten were sent to the virological laboratory of the National Institute for Public
Health and the environment (RIVM) in Bilthoven, which made diagnostic testing available. Reference materials were obtained from the laboratory in Marseille (CNRIRBA). Due to a lack of information about the date of onset of illness, all samples were tested by RT-PCR and for chikungunya-specific IgM and IgG-antibodies when
RT-PCR was negative. Because transport of samples is both expensive and time consuming, the RIVM assists the local laboratories of Sint Maarten and Curaçao to implement serological testing indirect fluorescent-antibody (IFA) from the second quarter of 2014.

A standard case reporting form is used to collect information on chikungunya cases (based on the case definition). Reports from undifferentiated fever (>38.5°C), which might include chikungunya cases, are collected on a weekly basis from sentinel sites.

Control measures
Mosquito control services are present on Sint Maarten and routine measures are the same as for the control of dengue fever: fogging with adulticides (Evoluer 4-4; active ingredient: permethrin/piperonyl butoxide), removal of breeding sites, application of larvicides in water containers and health education on prevention of mosquito bites. Upon arrival, tourists, which are paramount for the regional economy of the islands, are informed of the ongoing outbreak of chikungunya and advised to take personal protection measures against mosquito bites. The local authorities make use of the preparedness and response plan of the United States
(US) Centers for Disease Control and Prevention (CDC) for introduction of chikungunya virus in the Americas, which was introduced during two workshops in 2012 hosted by Pan American Health Organization (PAHO)
[14]. Specialists from the CARPHA and the PAHO have provided expert advice concerning control in January
2014 by means of a work visit to Sint Maarten. General practitioners have been informed of the presence of the disease and an intensified surveillance has been initiated by the Public Health Authority of Sint Maarten. The ministry of Health has initiated procedures in order to make chikungunya cases notifiable for the BES islands.
General practitioners and specialists on all other overseas territories in the Netherlands have been informed of this emerging epidemic, and have been advised concerning diagnostic testing since the end of December
2013.

Overseas territories of the United Kingdom

The overseas territories of the United Kingdom (UK) in the Caribbean region comprise five territories of which three (Anguilla, British Virgin Islands and Montserrat) are located within the Lesser Antilles east of Puerto Rico and two (Cayman Islands and Turks and Caicos Islands) in the western Caribbean in the Greater Antilles. The total population of these territories is around 136,000 and ranges from just over 5,000 (Montserrat) to around
36

Epidemiological situation
British Virgin Islands: three cases of chikungunya were confirmed by CAPHA on Jost Van Dyke island in the
British Virgin Islands on 13 January 2014 (Figures 2 and
3). The cases had onset of symptoms on the 15, 17 and
25 December 2013. The symptom profile of the three cases consisted of fever (>38.5°C) and severe arthralgia. Retro-orbital pain, back pain, and rash were not present. There was no history of travel. These three cases tested positive for chikungunya and were negative for dengue by PCR. As of 27 March 2014, a total of seven autochthonous cases have been confirmed in the British Virgin Islands, all from Jost Van Dyke island; the most recent case with onset of illness on 5 February
2014 (week 6 2014).
Anguilla: On 31 January 2014, one case of chikungunya, believed to be imported from Saint Martin was diagnosed in Anguilla and confirmed by CARPHA in Trinidad. As of 27 March, a total of 14 confirmed cases (13 autochthonous and one imported) have been reported in Anguilla with onsets of illness between 27
January and 16 February 2014.
The case definition used is in line with the one provided by CARPHA: a suspected case is a patient with acute onset of fever >38.5⁰C and severe arthralgia or arthritis not explained by other medical conditions, and who resides or has visited epidemic or endemic areas within two weeks prior to the onset of symptoms; a probable case is defined as a suspected case with a positive result for chikungunya by IgM enzyme-linked immunosorbent assay (ELISA); and a confirmed case is a suspected case with a positive result for chikungunya by viral isolation, RT-PCR or four-fold increase in chikungunya virus specific antibody titres (samples collected at least 2 to 3 weeks apart).
Microbiological investigation
Molecular PCR testing for chikungunya is undertaken by CARPHA in Trinidad and the first positive samples in
British Virgin Islands were sent to the US CDC for verification, as these were the first cases confirmed by the
Trinidad laboratory.
Control measures
The vector control unit of the Environmental Health
Division of the British Virgin Islands performed control activities and monitoring as well as house to house inspections and education at the time of the initial reports. They have been monitoring mosquito indices on Jost Van Dyke. Surveillance activities have www.eurosurveillance.org been increased. The Ministry of Health and Social
Development in Anguilla continues to work in collaboration with the relevant agencies to ensure that the appropriate preventative measures are implemented to reduce and contain the spread of the virus. Measures include mass education of the public to raise awareness of symptoms and prevention, fogging in areas where confirmed or suspected cases of chikungunya have been reported and engaging with port health teams at sea and airports in order to implement appropriate controls.

Discussion

Chikungunya is endemic in Africa, south-east Asia and on the Indian subcontinent with outbreaks occurring beyond the well-known endemic areas from 2005
(Figure 1). Compared to this historical occurrence, this is the first documented outbreak of chikungunya in the
Americas. The virus in the Caribbean belongs to the
Asian genotype [13]. It might have been introduced by travellers from Asia where outbreaks were reported in
2013. With the increased transmission of chikungunya in Asia and Africa in the last decade, the Caribbean region has been considered highly vulnerable [14]. The primary vector, Ae. aegypti, is widespread in the region
[15], but also Ae. albopictus is found in the Americas and on a number of Caribbean islands [16]. The latter species has not been found in French Guiana, the French
Caribbean islands nor the Dutch Caribbean territories but the climate suitability model revealed that the area is highly suitable for this vector species [15-17]. The presence of a human population naïve to the chikungunya virus, competent vectors in the region and the intense movement of people into and between islands are factors that most likely contributed to the extension of the virus circulation. Indeed, contacts between the islands are high as exemplified by the increased traffic between Saint Martin/Sint Maarten and the British
Virgin Islands as a consequence of a boat show in the
British Virgin Islands in December 2013. Besides the reported affected areas of the French, Dutch and British overseas territories, confirmed cases were reported from Dominica and Saint Kitts and Nevis (Figure 3 and
[18,19]) and the first autochthonous transmission on the continent was confirmed in French Guiana 11 weeks after the first confirmed case on Saint Martin (week 8
2014). The establishment of autochthonous transmission following importation of viraemic patients in other territories of the Americas is expected and will likely have a significant public health impact in the region.
Surveillance in the region, which is well established for dengue, has been intensified and laboratory testing has been strengthened in collaboration with regional or international reference laboratories. Further, a close follow-up of the situation and co-ordinated surveillance and control within the regions is still needed.
The vulnerability of Europe for the transmission of chikungunya virus and other arboviruses was recognised prior to 2007 [20] and confirmed with the first chikungunya outbreak in Italy in 2007 [8,21,22]. For onward www.eurosurveillance.org transmission to occur, the introduction of this virus into
Europe would need to coincide with high vector abundance and activity i.e. during the summer season in the EU. Hence, chikungunya outbreaks in the northern hemisphere are of bigger concern for the EU than those in the southern hemisphere [23]. During the period from
2008 to 2012, 475 imported chikungunya cases have been reported by 22 EU/European Economic Area (EEA) countries [7]. Most cases originated from Asia (one third from India, otherwise Indonesia, Maldives, Sri
Lanka and Thailand) and Africa (including islands from the Indian Ocean). Temporal clusters of chikungunya cases imported in the EU are largely synchronous with large outbreaks in endemic countries as reported for
Germany [24]. The occurrence and possible establishment of chikungunya in the Caribbean region adds an additional possible source of introduction of the virus.
Because of the relatively intensive traffic between the overseas territories and the EU, introduction of chikungunya in Europe can be anticipated and blood safety measures could be considered [25]. It should be noted that both autochthonous dengue cases in France in
2010 and 2013 followed the introduction of a viraemic patient from the French Caribbean overseas territories.
The introduction of chikungunya viraemic persons will most likely not lead to onwards transmission in Europe during the winter season as the vectors are not active during this season. However, vigilance is needed if the outbreak in the Caribbean region continues and overlaps with the mosquito vector season in areas where
Ae. albopictus is established in continental Europe.
Firstly reported in Europe in 1979 in Albania [26], the mosquito vector Ae. albopictus has continuously expanded its distribution in the EU. To date this species has colonised almost all Mediterranean countries and has been found introduced, without establishment in Austria, Belgium, Czech Republic, in more northern localities in France, and the Netherlands,
[10]. Ae. albopictus can reach high densities from July to September around the Mediterranean where it is established [27]. Ae. aegypti has recently established on Madeira and is found around the Black Sea coast.
The A226V mutation of ECSA chikungunya virus has increased the transmissibility of the chikungunya virus by Ae. albopictus [11] and vector competence studies using Ae. albopictus populations from France showed that both the mutated and non-mutated ECSA chikungunya strains can be transmitted by local mosquito populations [28]. The chikungunya strain currently circulating in the Caribbean region does not belong to the
ECSA genotype but to the Asian genotype. The strain is related to strains recently identified in Indonesia,
China and the Philippines [13]. The competence of the
European population of Ae. albopictus to transmit this chikungunya strain needs investigation.
In conclusion, spread and establishment of the disease in the Caribbean and other regions in the Americas can be anticipated given the high connectivity between the affected and non-affected areas and the widespread
37

occurrence of efficient vectors. Also, the risk of introduction of the disease to the EU from the affected territories in the Caribbean should be considered especially in the context of the next mosquito season in Europe.
Clinicians should be aware that, besides dengue, chikungunya should be considered among travellers currently returning from the Caribbean region. The clinical picture of both infections can be similar and might be a challenge for clinicians that are not familiar with the clinical presentation of these infections.
Acknowledgements
We would like to thank the CVAGS in French Guiana,
Guadeloupe, Martinique, Saint Barthélemy and Saint Martin, the microbiologists and the staff of the National Reference
Laboratories (CNR in Irba Marseille, CNR in IPG Cayenne,
RIVM-IDS in Bilthoven) and the public hospital microbiological laboratory of virology for their high commitment. We are also grateful to the sentinel doctors from Guadeloupe,
Martinique, Saint Barthélemy, Saint Martin, and Sint
Maarten, and the infectious diseases specialists working at the hospital Centres in the different territories and the private microbiological laboratories.

Conflict of interest
None declared.

Authors’ contributions
Wim Van Bortel coordinated and drafted the manuscript, and reviewed final document for accuracy; Frédérique Dorleans coordinated and drafted the part of the manuscript on the
French Caribbean territories and reviewed the different versions of the MS / Permanent member of the outbreak team management in Martinique; Jacques Rosine and Alain Blateau are permanent members of the outbreak management team in Martinique and permanent member of the regional outbreak management team (French Caribbean territories) and responsible for the data collection management and interpretation; Dominique Rousset form the French National
Reference Center for Arboviruses is head of the associated lab for the French departments of the Americas and involved in virological diagnosis and manuscript proofreading; Fatiha
Najioullah of the University Hospital Laboratory of virology,
Fort-de-France, Martinique manages the molecular virological diagnosis and in involved in virological diagnosis and manuscript proofreading ; Raymond Césaire Head of the virology laboratory of the University Hospital Laboratory of virology, Fort-de-France, Martinique was involved in the implementation of virological diagnosis; Séverine Matheus of the French National Reference Center for Arboviruses is deputy head of the associated laboratory for the French departments of the Americas and involved in virological diagnosis and manuscript proofreading; Isabelle Leparc-Goffart Head of the French National Reference Center for Arboviruses and coordinating all French territories is involved in virological diagnosis and participated to the writing of the manuscript;
Olivier Flusin of the French National Reference Center for
Arboviruses, is involved in virological diagnosis and editing of the manuscript; Christine M Prat of the French National
Reference Center for Arboviruses is involved in virological diagnosis and editing of the manuscript; Vanessa Ardillon is a permanent member of the outbreak management team in
French Guyana and member of the regional outbreak management team (French Caribbean territories) and responsible

38

for management, data collection and interpretation; Elsa
Balleydier is temporary member of the outbreak management team in Guadeloupe, Saint Martin and Saint Barthélemy and is involved in the data collection, management and interpretation; Luisiane Carvalho is a permanent member of the outbreak management team in French Guyana and member of the regional outbreak management team (French Caribbean territories) and responsible for management, data collection, and interpretation; Audrey Lemaître is a temporary member of the outbreak management team in Saint Martin and Saint
Barthélemy and involved in the data collection, management and interpretation; Lucie Léon is a temporary member of the outbreak management team in Saint Martin and Saint
Barthélemy and involved in the data collection, management and interpretation; Harold Noël, Véronique Servas,
Caroline Six and Manuel Zurbaran are temporary members of the outbreak team management in Saint Martin and
Saint Barthélemy and responsible for data collection, management and interpretation; Anne Guinard from the French
Institute for Public Health Surveillance, Toulouse, France was involved in data collection and interpretation; Hans van den Kerkhof coordinates the international aspects of control for the Netherlands, and coordinating author of the
Netherlands contribution to the Euro Roundup Chikungunya
; Ewout Fanoy is responsible for the registration of cases, epidemiological analysis and reviewing manuscript; Marieta
Braks is an entomologist at the RIVM and advisor/trainer for mosquito control programmes on Sint Maarten. She was involved in the editing and proof reading of the manuscript;
Johan Reimerink is a senior staff in the virological Laboratory in RIVM, and responsible for Diagnostic Testing of outbreak samples; Maria Henry is in charge of surveillance and control activities Sint Maarten and reviewed the manuscript;
Corien Swaan coordinates the international aspects of control for the Netherlands and contributed to the writing of the manuscript; Ronald Georges provided epidemiological information from the British Virgin Islands and reviewed manuscript; Lynrod Brooks: provided epidemiological information from Anguilla and reviewed manuscript; Joanne Freedman: provided the UK background, coordinated the contribution of additional epidemiological information from the UK overseas territories and reviewed final document for accuracy;
Bertrand Sudre coordinated and developed the historical overview and the transmission map and reviewed final document ; Herve Zeller, head of the emerging and vector borne disease programme of ECDC, reviewed final document for accuracy. All authors have read and approved the manuscript.

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Research articles

Local and regional spread of chikungunya fever in the
Americas
S Cauchemez (simon.cauchemez@pasteur.fr)1, M Ledrans2, C Poletto3,4 , P Quenel5, H de Valk6, V Colizza3,4,7, P Y Boëlle3,4
1. Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, Paris, France
2. French Institute for Public Health Surveillance, Regional office for French West Indies and French Guyana, Fort de France,
France
3. INSERM, UMR-S 1136, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Paris, France
4. Sorbonne Universités, UPMC Univ Paris 06, UMR-S 1136, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Paris,
France
5. Institut Pasteur de Guyane, Cayenne, France
6. French Institute for Public Health Surveillance, Paris, France
7. Institute for Scientific Interchange (ISI), Torino, Italy
Citation style for this article:
Cauchemez S, Ledrans M, Poletto C, Quenel P, de Valk H, Colizza V, Boëlle PY. Local and regional spread of chikungunya fever in the Americas. Euro Surveill.
2014;19(28):pii=20854. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20854
Article submitted on 01 July 2014/ published on 17 July 2014

Chikungunya fever (CHIKV), a viral disease transmitted by mosquitoes, is currently affecting several areas in the Caribbean. The vector is found in the Americas from southern Florida to Brazil, and the Caribbean is a highly connected region in terms of population movements. There is therefore a significant risk for the epidemic to quickly expand to a wide area in the Americas. Here, we describe the spread of CHIKV in the first three areas to report cases and between areas in the region. Local transmission of CHIKV in the Caribbean is very effective, the mean number of cases generated by a human case ranging from two to four. There is a strong spatial signature in the regional epidemic, with the risk of transmission between areas estimated to be inversely proportional to the distance rather than driven by air transportation. So far, this simple distance-based model has successfully predicted observed patterns of spread. The spatial structure allows ranking areas according to their risk of invasion. This characterisation may help national and international agencies to optimise resource allocation for monitoring and control and encourage areas with elevated risks to act.

Introduction

Chikungunya fever is caused by the chikungunya virus, an alphavirus that is transmitted by several species of mosquitoes, including Aedes albopictus and Ae. aegypti
[1]. In the last decade, large outbreaks of chikungunya fever have been reported in the Indian Ocean region
[2], with millions of people experiencing incapacitating arthralgia, fever and rashes [3,4]. Transmission was sustained even in places with high standards of sanitary organisation [5].

www.eurosurveillance.org

An outbreak of chikungunya fever is currently affecting an increasing number of areas in the Caribbean [6-8].
Figure 1 shows areas that reported at least one autochthonous case by 15 June 2014. The figure also shows the timeline of reporting. The first area reporting cases was Saint Martin (9 December 2013) with symptom onset of the first documented case on 5 October 2013.
Further reports quickly followed from two other French territories, Martinique on 19 December 2013 and
Guadeloupe on 28 December 2013. By 15 June 2014, 16 areas had reported at least one autochthonous case.
This rapid expansion constitutes a source of concern for public health in the Americas [8]. The mosquito vector is found in a wide geographical zone that goes from
South Florida to Brazil [10]. The potential for geographical expansion is therefore considerable and extends far beyond the areas currently affected. Moreover, the
Caribbean is a highly connected area with frequent exchanges among the islands in the region, with mainland America and with Europe: more than 10 million international visits are reported each year by the World
Tourism Organization, including 25% from Europe [11].
These important connections increase the risk of the current epidemic expanding quickly to a wider area in the Americas. Furthermore, the epidemic generates importations of cases into Europe, where the mosquito species Ae. albopictus is well established in many countries, primarily around the Mediterranean [9,12]. As of
1 July 2014, 98 imported laboratory-confirmed cases have been reported for metropolitan France alone [13].
In order to support preparedness and response planning in affected areas and those at risk of invasion
(i.e. arrival of the disease in the area), it is important that we understand better the local and regional
41

Figure 1
Chikungunya fever in the Caribbean, as of 15 June 20141

Dominican Rep (Mar 25, 2014)
US Virgin Islands (Jun 11, 2014)

Cuba (Jun 11, 2014)

British Virgin Islands (Jan 13, 2014)
Anguilla (Feb 7, 2014)
Haiti (May 10, 2014)

Saint Martin (Dec 9, 2013)
PUERTO RICO

Saint Barthelemy (Dec 28, 2013)

JAMAICA

Antigua and Barbuda (Apr 25, 2014)
St Kitts and Nevis (Feb 20, 2014)

TIMELINE OF REPORTING
Dec

Jan

Feb

Mar

Apr

May

Guadeloupe (Dec 28, 2013)

Jun

Dominica (Jan 16, 2014)
Martinique (Dec 19, 2013)
St. Lucia (May 13, 2014)
St. Vincent and the Grenadines (Apr 25, 2014)

VENEZUELA
COLOMBIA

French Guyana (Feb 18, 2014)
GUYANA
SURINAME

Areas that reported at least one laboratory-confirmed autochthonous case of chikungunya fever are coloured according to the timeline of reporting [6]. The first date of symptom onset was 5 October 2013, on Saint Martin.

Box
List of areas included in the assessment of chikungunya virus transmission (n=40)

Anguilla, Antigua and Barbuda, Aruba, Bahamas, Barbados,
Belize, British Virgin Islands, Cayman Islands, Colombia,
Costa Rica, Cuba, Curacao, Dominica, Dominican Republic,
El Salvador, Florida, French Guiana, Grenada, Guadeloupe,
Guatemala, Guyana, Haiti, Honduras, Jamaica, Martinique,
Mexico, Netherlands Antilles, Nicaragua, Panama, Puerto
Rico, Saint Barthelemy, Saint Kitts and Nevis, Saint Lucia,
Saint Martin, Saint Vincent and the Grenadines, Suriname,
Trinidad and Tobago, Turks and Caicos Islands, United
States Virgin Islands, Venezuela.

42

dynamics of spread of chikungunya fever in the
Caribbean. Firstly, how effective is transmission of the disease in the Caribbean? Answering this question is important to assess the potential for large and explosive outbreaks as seen previously in the Indian Ocean region. Secondly, we need to understand the regional dynamics of spread and their determinants to assess which areas currently are at risk of invasion, to help national and international agencies with resource allocation, technical support and planning, and to encourage areas with elevated risks to act. This is essential in order to reduce disease burden in the Americas, but also to reduce the number of imported cases in Europe.
Here, we provide the first assessment of the effectiveness of transmission of the virus in the Caribbean and of the factors explaining the spread at the regional level. www.eurosurveillance.org

Methods

In the French overseas territories (Saint Martin,
Martinique and Guadeloupe), detailed data were collected by Cire Antilles-Guyane, using different approaches as the health authorities adapted to the situation. At first, an investigation was started around suspected or clinical cases with retrospective identification of other suspected cases in the neighbourhood.
Virological confirmation was undertaken for most of the clinically suspected cases by the two laboratories of the national reference centre (Marseille and Cayenne).
As the number of cases increased, existing surveillance networks based on general practitioners (GP) were asked to monitor clinical cases according to the case definition (patient with onset of acute fever >38.5
°C and severe arthralgia of hands or feet not explained by another medical condition). The surveillance network comprised 100% of the GPs on Saint Martin (15

Data collection

We selected 40 areas (countries or territories) around the Caribbean which overlap with areas infested by
Ae. aegypti mosquito [10] and where dengue is present
[14,15] in central America (Box).
We defined areas officially affected by chikungunya fever as those reported to have had at least one laboratory-confirmed autochthonous case of chikungunya fever in the ProMED-mail alerts [6], the Pan American
Health Organization [16] or the Caribbean Public Health
Agency [17]. The date of the first report was also recorded. Figure 2
Reproduction number of chikungunya fever in the Caribbean, 2014
A

B

1000

Guadeloupe

750
500
250
0
3000

Incidence

Martinique

2000

1000

0

300

Saint Martin

200
100

2014−15

2014−14

2014−13

2014−12

2014−11

2014−10

2014−09

2014−08

2014−07

2014−06

2014−05

2014−04

2014−03

2014−02

2014−01

2013−52

2013−51

2013−50

2013−49

2013−48

0
0

1

2

3

4

5

Reproduction Number

Week

A Epidemic curves based on clinical surveillance systems in general practice on three French islands (bars). An exponential fit to the whole epidemic is shown as a dashed line.
B. Estimates of the reproduction number based on the exponential growth for the 10 time periods of four weeks or more with the best fits. The boxplots show the median, interquartile interval and range of the 10 point estimates.

www.eurosurveillance.org

43

Figure 3
Areas in the Caribbean officially affected by chikungunya fever on 15 June 2014 and prediction in the distance model (A) and the air transportation model (B)
A- Distance model

B- Air transportation model

Anguilla
Saint Barthelemy
Saint Kitts and Nevis
Antigua and Barbuda
British Virgin Islands
United States Virgin Islands
Guadeloupe
Dominica
Martinique
Saint Lucia
Saint Vincent and the Grenadines
Puerto Rico
Grenada
Barbados
Trinidad and Tobago
Netherlands Antilles
Curacao
Aruba
Dominican Republic
Haiti
Turks and Caicos Islands
Venezuela
Guyana
Jamaica
Bahamas
Suriname
Cuba
Cayman Islands
French Guiana
Colombia
Panama
Nicaragua
Honduras
Florida
Costa Rica
Belize
El Salvador
Guatemala
Mexico

Florida
Puerto Rico
Colombia
Venezuela
Dominican Republic
Mexico
Panama
Costa Rica
Curacao
Jamaica
Trinidad and Tobago
Bahamas
United States Virgin Islands
Guatemala
Cuba
Guadeloupe
Aruba
Honduras
Saint Barthelemy
Haiti
Nicaragua
El Salvador
Barbados
British Virgin Islands
Saint Kitts and Nevis
Antigua and Barbuda
Netherlands Antilles
Martinique
Cayman Islands
Saint Lucia
Dominica
Guyana
Suriname
Belize
Turks and Caicos Islands
Grenada
Saint Vincent and the Grenadines
Anguilla
French Guiana

0.0

0.2

0.4

0.6

0.8

Probability territory officially affected

0.0

0.2

0.4

0.6

0.8

Probability territory officially affected

The grey bars give the probability predicted by the model that the area should be officially affected by 15 June 2014, sorted in decreasing order. The red dots indicate areas that were officially affected by 15 June 2014 according to the (data). The red dots indicate areas that actually were officially affected by 15 June 2014 according to the data. A good fit is suggested when most of the red dots appear at the top of the pyramid. of 15) and around 20% on Martinique and Guadeloupe.
Virological confirmation was no longer systematically undertaken as the number of cases increased.
Commercial air connections and 2013 data for volume of passengers between airports of the region were obtained from the International Air Transport
Association [18,19]. These data correctly captured multi-leg flight trajectories, i.e. if a person flew from
Florida to Jamaica via Puerto Rico, the recorded itinerary would be the Florida to Jamaica journey. Distances between the centroids of the areas were computed.

Characterising local transmission on
Saint Martin, Martinique and Guadeloupe

The human-to-human initial reproduction number R
(mean number of secondary cases generated by a human case) was computed using the exponential
44

growth method [20]. We explored the variability of these estimates by analysing all time periods of four weeks or more in the epidemic curves and reporting the 10 periods for which our exponential growth model had the best fit to the data (as measured by the deviance R-squared statistic [21]). Additional details can be found in the supplementary material* that can be accessed at https://docs.google. com/file/d/0B0pDXBmlKKGMRW9ucWRpaV V5bDQ/ edit?pli=1. Characterising regional spread

The transmission paths between areas were analysed under the hypotheses that the risk of invasion arose from previously invaded areas with data available as of
15 June 2014 [22]. We considered that Saint-Martin was the first invaded territory, with a first case on 5 October
2013. For other areas, a delay of on average 30 days www.eurosurveillance.org was allowed between invasion and reporting. Different mathematical models were developed in which the instantaneous risk of transmission between areas depended on population size, distance, air traffic volume or a combination thereof. The models were fitted by Markov chain Monte Carlo sampling [23]. Goodness of fit was assessed by determining how well the models agreed with the set of areas officially affected by the time the analysis was performed. Finally, we used the best model to predict areas with the highest risk of invasion. As we have been using this model since early
2014, we also evaluated retrospectively short-term predictions that were made with data available on 15
January 2014 and on 30 March 2014. Technical details are available in the supplementary material*.

reasonable, leading to estimates of the reproduction number in the range 2 to 4 (Figure 2). The reproduction number was estimated to be slightly higher on
Guadeloupe than on Martinique, due to a renewed outbreak starting in week 10 of 2014 on Guadeloupe.

Regional spread

A marked geographical pattern of the spread was apparent (Figure 1), as 12 of 16 officially affected areas were situated in a relatively small geographical zone between the British Virgin Islands in the north-west and Saint Vincent and the Grenadines in the south-east.
We found that this pattern was best explained by making the risk of transmission between areas inversely proportional to distance. If we exclude the seed location Saint Martin, 15 areas were officially affected. Of these 15, 11 were at the top of the list of areas predicted to be at highest risk of invasion by this simple model based on distance (Figure 3A). In contrast, only one of 15 officially affected areas was at the top of the list if the risk of transmission was instead assumed to depend on air passenger flows, indicating that air passenger flow was a poor predictor of transmission

Results
Local transmission on Saint Martin,
Martinique and Guadeloupe

Surveillance of clinically suspected cases started in weeks 48, 49 and 52 of 2013 on Saint Martin, Martinique and Guadeloupe, respectively. The fit of an exponential increase to the first weeks of each outbreak was

Figure 4
Short-term predictions of the distance model performed on different dates in the chikungunya fever epidemic in the
Caribbean with data as available on these dates
A. 15 January 2014
Anguilla
St Kitts and Nevis
US Virgin Islands
Antigua and Barbuda
Dominica
St Lucia
St Vincent and the Grenadines
Grenada
Puerto Rico
Barbados
Trinidad and Tobago
Dominican Republic
Netherlands Antilles
Curacao
Haiti
Aruba
Turks and Caicos Islands
Venezuela
Guyana
Jamaica
Bahamas
Cuba
Suriname
Cayman Islands
French Guiana
Colombia
Costa Rica
Panama
Guatemala
Honduras
Florida
Nicaragua
El Salvador
Belize
Mexico

B. 30 March 2014

C. 15 June 2014

Antigua and Barbuda
US Virgin Islands
St Lucia
St Vincent and the Grenadines
Puerto Rico
Barbados
Grenada
Trinidad and Tobago
Haiti
Netherlands Antilles
Curacao
Turks and Caicos Islands
Aruba
Venezuela
Suriname
Guyana
Jamaica
Bahamas
Cuba
Colombia
Cayman Islands
Panama
Nicaragua
Costa Rica
Honduras
Florida
Belize
El Salvador
Guatemala
Mexico
0.0

0.2

0.4

0.6

0.8

Probability of invasion

1.0

Grenada
Barbados
Puerto Rico
Trinidad and Tobago
Netherlands Antilles
Curacao
Aruba
Turks and Caicos Islands
Venezuela
Bahamas
Jamaica
Cayman Islands
Suriname
Guyana
Florida
Colombia
Nicaragua
Honduras
Panama
El Salvador
Belize
Costa Rica
Guatemala
Mexico
0.0

0.2

0.4

0.6

0.8

Probability of invasion

1.0

0.0

0.2

0.4

0.6

0.8

1.0

Probability of invasion

Dark bars indicate the probability of areas already invaded at the time the analysis was performed. Light bars give the probability that the area would be invaded in the 75 days following the time of the analysis. For analyses performed on 15 January and 15 June 2014, we highlight in red the areas that became officially affected in the 75 days following the date of analysis.

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45

Figure 5
Most probable source of transmission for areas that are officially affected by chikungunya fever and for those that may already be invaded but have not yet reported cases

St. Kitts and Nevis

Dominica
Antigua and Barbuda
St. Barthelemy

Guadeloupe
St. Martin
US Virgin Islands
British Virgin Islands

Puerto Rico
Dominican Republic

Haiti

Martinique

Anguilla

French Guiana

Cuba

Saint Lucia
Saint Vincent and the Grenadines

Barbados
Grenada
Transmission tree for areas officially affected (in red) and for those that have at least 20% probability of already being invaded (in grey). The transmission tree is visualised in a topological space where areas are organised in successive layers starting from Saint Martin according to their most probable source of transmission. Most probable transmission links are plotted in green; other links with probability larger than 3% are plotted in grey. The thicker the arrow, the higher the probability of transmission.

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www.eurosurveillance.org

(Figure 3B). Population sizes of areas were not found to significantly affect transmission (see supplementary material*). Figure 4 presents predictions made with this model on 15 January 2014 (Figure 4A) and on 30 March 2014
(Figure 4B). It shows the risk of being already invaded at the time of the analysis or of being invaded in the following 75 days, based on data available at the time.
Overall, performance of the model has been good, as most areas officially affected in the following 75 days were among those that had the highest predicted risk of invasion. Of 11 areas officially affected during this period, French Guiana and Cuba were the only two with low predicted risks.
Figure 4C shows predictions of the model with data available on 15 June 2014. Grenada, Barbados and
Puerto Rico currently have the largest predicted probability of being invaded in the 75 days following the analysis (36%). We note that heterogeneity in the predicted risk of invasion has decreased as Chikungunya has expanded in the region, with the standard deviation in the predicted risk declining from 27% on 15
January 2014 to 15% on 15 June 2014.
Assuming that Saint Martin was the seed of infection in the region, Figure 5 shows the most likely path of transmission for areas that were either officially affected or likely to be already invaded although autochtonous cases had not been reported. The first round of invasion included Martinique, Guadeloupe, Saint Barthélemy,
British Virgin Islands and Anguilla. The second round of invasion eventually led to eight new invaded areas, including Dominica and French Guiana. Four rounds were necessary for the disease to reach Cuba. Looking at the reconstructed transmission tree and restricting the analysis to areas that were officially affected, we found that the median distance between two areas predicted to have transmitted chikungunya to each other was 476 km (95% CI: 16–2,040). It was 173 km (95% CI:
16–451) and 626 km (95% CI: 54–2,043), respectively, for areas in the first and in subsequent rounds of the regional epidemic.

Discussion

The chikungunya virus has found a propitious environment for transmission in the Caribbean. All areas of the
Caribbean and Central America are at risk of invasion, although with important heterogeneities in their predicted risks. Our analysis provides a quantitative basis for informed policy making and planning.
Transmission of chikungunya fever was consistently estimated to be effective in the three French territories that first reported cases (Saint Martin, Martinique and
Guadeloupe). Estimates of the reproduction number
R ranged from 2 to 4, similar to what was reported in the Indian Ocean region [5,24], making large and fastgrowing outbreaks possible. With the largest estimate,
Guadeloupe may end up with the largest attack rate if www.eurosurveillance.org transmission goes on unchanged. Interestingly, incidence there showed sustained increase only after the epidemic entered the largest city (Pointe à Pitre), suggesting heterogeneity in transmission. In Saint Martin, incidence has notably slowed down in the last weeks, despite large growth at first. Further investigation is required to find out how vector abundance, heterogeneity in population mixing and exposure explain these outcomes. These estimates of R were obtained under the assumption that the serial interval was 23 days
(see supplementary material*). Using a shorter duration for the gonotrophic cycle (three days vs four days) led to little change in the serial interval distribution
(two days) and less than 5% variation on the estimates of R. With higher daily mortality in mosquitoes (15% instead of 10%), the serial interval was shorter, and the estimates of R were reduced by ca 20%.
Sustained transmission in the French islands has been in contrast with the limited number or absence of cases reported in some nearby areas. This could partly be explained if French territories were invaded first so that they had more time to build up large numbers of cases. However, heterogeneity in reporting is also likely to be involved, as some areas only reported the disease when it had already been responsible for hundreds of cases.
Indeed, a difficulty in the analysis of the regional diffusion of chikungunya fever has been the imperfect documentation of areas that were affected and of the dates when they were invaded. This is due to variable delays between (unobserved) dates of invasion and reporting of the first autochthonous cases. We did not model heterogeneities in the capabilities of the different areas to identify cases, as supporting data are lacking and this would therefore have been mostly subjective and added uncertainty to the analysis. But we used state-of-the-art data augmentation techniques
[25-27] to overcome uncertainty about timing. In our baseline scenario, we assumed an average 30-day reporting delay but analysed alternative scenarios with shorter and longer delays in the supplementary material*. Reducing the reporting delay did not change the relative order of areas by risk of invasion but led to reduced probabilities of invasion in the near future.
Unfortunately, we did not have independent data to back up the baseline assumption of an average 30-day delay in reporting.
To understand and predict regional spread, we postulated that importation of infected humans or mosquitoes by usual transportation routes was likely to be responsible for invasion of new areas. Most islands are served by air carriers, but travelling by boat, ferries and cruisers is also very common. Up to now, areas officially affected by chikungunya fever have presented smaller air passenger flows than those not yet affected (daily average: 797 as opposed to 2,476). It is therefore not surprising that air transportation data could not reproduce the patterns of spread seen so far
47

(Figure 3B). A direct assessment of alternative modes of transportation, including boats and cruises, was not possible due to a lack of detailed data on these routes.
To overcome this limitation, we used standard geographical models where connections between areas depend on distance and population sizes [28-30]. We found that the spatial structure of the epidemic was most consistent with a model in which the strength of a connection was inversely proportional to the distance.
Overall, our results suggest that short-range transportation such as boats and cruises hopping between islands are likely to have played a substantial role in the spread observed in the early phase of the chikungunya outbreak in the Carribean.
The good fit of this distance model to current data
(Figure 3A) and its successful predictions so far (Figure
4, panels A and B) give us some confidence in the shortterm predictions of this model (Figure 4C). However, the relative importance of the transmission routes may change as the epidemic spreads, which could increase the risk to more distant areas in the longer term. In that respect, we note an apparent increase in the median distance of transmission between the first and subsequent waves in the regional epidemic. Given the current absence of correlation between available long-range air transportation data and disease spread, long-term predictions for international spread are harder to make.
The propensity of an area to get invaded and to transmit is expected to depend on vector activity and case numbers, respectively. Here, we used qualitative data on the presence of the Ae. aegypti mosquito [10], which are supported by recent reports on dengue virus circulation [14,15], to characterise vector activity. The vector was present in all areas included in our analysis
[10,14,15]. Due to the lack of adequate data, we were unable to modulate the risk of invasion with more quantitative indicators of vector activity. Efforts to construct quantitative maps of vector activity should be a priority to improve model predictions. If they become available, data on incidence of cases in the invaded areas may improve the fit further, although this was not shown to be the case in the spatial analysis of other outbreaks [22]. Despite these limitations, shortterm predictions of the model have been good (Figure
4, panels A and B). Improved predictions may require taking seasonality into account, as vector abundance may change with the seasons. The range of temperature is limited in the Caribbean islands (between 26
°C and 29 °C in Saint Martin), but larger changes are expected as we move away from the equator. Seasonal changes in the number of passengers to and from the
Caribbean must also be considered when studying the risk of importation to Europe.
In conclusion, we have shown that chikungunya fever is an important threat in the Americas. The high transmissibility may lead to fast-growing and large outbreaks. Regional dissemination is under way, so far

48

with a simple geographical pattern, which is relevant for optimising the monitoring of areas.
*Note:
Supplementary information made available by the authors on an independent website is not edited by Eurosurveillance, and Eurosurveillance is not responsible for the content.
The material can be accessed at: https://docs.google.com/ file/d/0B0pDXBmlKKGMRW9ucWRpaVV5bDQ/edit?pli=1. Acknowledgements
We thank IMMI, EU FP7 PREDEMICS, Labex IBEID, NIH MIDAS and HARMSflu for research funding.

Conflict of interest
None declared.

Authors’ contributions
ML, PQ, HDV provided the data. SC, CP, VC, PYB analysed the data. SC and PYB designed the analysis and wrote the first draft. All authors edited and commented the paper.

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Rapid communications

Two cases of Zika fever imported from French Polynesia to Japan, December 2013 to January 2014
S Kutsuna (sonare.since1192@gmail.com)1, Y Kato1, T Takasaki2, M L Moi2, A Kotaki2, H Uemura1, T Matono1, Y Fujiya1, M
Mawatari1, N Takeshita1, K Hayakawa1, S Kanagawa1, N Ohmagari1
1. National Center for Global health and Medicine, Disease Control and Prevention Center, Tokyo, Japan
2. Department of Virology 1, National Institute of Infectious Diseases, Shinjukuku, Tokyo, Japan
Citation style for this article:
Kutsuna S, Kato Y, Takasaki T, Moi ML, Kotaki A, Uemura H, Matono T, Fujiya Y, Mawatari M, Takeshita N, Hayakawa K, Kanagawa S, Ohmagari N. Two cases of Zika fever imported from French Polynesia to Japan, December 2013 to January 2014 . Euro Surveill. 2014;19(4):pii=20683. Available online: http://www. eurosurveillance.org/ViewArticle.aspx?ArticleId=20683 Article submitted on 19 January 2014 / published on 30 January 2014

We present two cases of imported Zika fever to Japan, in travellers returning from French Polynesia, where an outbreak due to Zika virus (ZIKV) is ongoing since week 41 of 2013. This report serves to raise awareness among healthcare professionals, that the differential diagnosis of febrile and subfebrile patients with rash should include ZIKV infection, especially in patients returning from areas affected by this virus.
We report two cases of Zika fever in Japan, which were imported from French Polynesia, where on 6 November
2013 public health authorities reported an outbreak of subfebrile illness with rash due to Zika virus (ZIKV).
The epidemic started spreading across the archipelago beginning in week 41 of 2013 [1]. During weeks 42 to
52, the syndromic surveillance network reported 6,630 suspected ZIKV infection cases to the Bureau de Veille
Sanitaire. About 500 of these cases were tested at the
Institute Louis Malarde laboratory in Papeete for confirmation; 333 were confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) as
ZIKV infections [2]. The outbreak is currently ongoing and as of 13 January 2014, 361 laboratory-confirmed
Figure 1
Conjunctivitis in a case of imported Zika virus infection from French Polynesia, Japan, January 2014

Although the patient was afebrile upon examination, both bulbar conjunctivas appeared congested.

50

cases have been reported [3]. Symptoms of most ZIKV infection cases are mild and self-limited (mean duration of symptoms is 3–6 days). No hospitalisations for acute infection have been reported.

Case 1

A previously healthy Japanese man in his mid-20s presented to our hospital in mid-December 2013 after four days of fever (self-reported), headache, and arthralgia and one day of rash. He had visited Bora Bora in
French Polynesia, in the first week of December 2013 for six days for sightseeing with his partner. He did not use insect repellent during the trip. Upon examination, his body temperature was 37.2°C (99°F) and he had maculopapular rash on his face, trunk, and extremities. Other clinical examination results were normal.
Laboratory tests revealed leucopenia (3,300 ×106/L; norm: 3,500–8,500×106/L) and thrombocytopenia
(14,900×106 /L; norm: 15,000–35,000×106 /L). ZIKV
RNA was detected in serum using real-time RT-PCR performed at the National Institute of Infectious Diseases in Japan with primer-probe sets previously described
[4]; thus, we diagnosed the patient with Zika fever. His fever and other symptoms subsided a day after first presentation and his rash disappeared over the next few days.

Case 2

A previously healthy Japanese woman in her early 30s presented to our hospital in the beginning of January
2014 for retro-orbital pain, slight fever (self-reported), rash, and itches. Her retro-orbital pain and mild fever had appeared five days prior to her visit at our hospital, while the rash and itches appeared on the day before the visit. She had travelled to Bora Bora where she stayed for 10 days starting mid-December 2013 for sightseeing with a companion. The first symptoms occurred six days after this journey. She had used insect repellent during her travels, but reported mosquito bites. She was afebrile and in good general condition at the first presentation to the hospital.
On examination, both bulbar conjunctivas appeared

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Figure 2
Maculopapular rash on the back in a case of imported
Zika virus infection from French Polynesia, Japan,
January 2014

subsequently demonstrated that the virus has a wide geographical distribution, including eastern and western Africa, south and south-east Asia, and Micronesia
[8], where in 2007, an outbreak of Zika fever was reported on Yap Island [9].

Phylogenetic analysis of the Zika virus sequence retrieved from case 2

Phylogenetic analysis of the partial ZIKV E-protein genome sequence (470 bp, GenBank accession number:
AB908162*) obtained from the urine sample of case 2, shows that this sequence has 99.1% identity with the sequence of a ZIKV strain isolated from Cambodia in
2010 (GenBank accession number: JN860885), and
97.9% identity with the sequence of a ZIKV strain isolated in Yap islands in 2007 (GenBank accession number: EU545988) (Figure 3). The sequence from case 2 sample was also similar to previously identified ZIKV sequences of strains in Asia and Micronesia [8]. In the phylogenetic tree, these sequences formed a distinct cluster from that of sequences from Zika viruses of African origin. Further studies using full-length genome of the ZIKV will address the similarity between virus strains of the African and Asian clusters. congested (Figure 1). She had maculopapular rash on her face, trunk, and extremities (Figure 2).
Laboratory tests on the day of first presentation at the hospital revealed leucopenia (3,500×106/L; norm: 3,500–8,500×106/L) and thrombocytopenia
(14,400×106/L; norm: 15,000–35,000×106/L). Real-time
RT-PCR assays, performed at the National Institute of
Infectious Diseases, gave negative results for ZIKV
RNA in serum but presence of the virus was detected in urine. The patient was diagnosed with Zika fever.
Her leucocyte and platelet levels returned to the normal range 12 days after first presentation at the hospital. The positive versus negative ratios (P/N ratio) of Zika-specific IgM antibodies were positive in two serum samples collected on the first day at the hospital and five days later (P/N ratios = 2.4 and 9.8, respectively; ratios were considered positive when greater than or equal to 2.0). The neutralising antibody titres of the serum in these two consecutive samples were
PRNT50 =1:20 and PRNT50 =1:1,280, respectively.

Background

Zika fever is a febrile or subfebrile illness caused by ZIKV, which mainly spreads through the bite of infected mosquitoes. ZIKV is a member of the family
Flaviviridae, which includes dengue viruses, West Nile, and yellow fever viruses [5]. The most common symptoms reported in confirmed ZIKV infections are fever, headache, malaise, maculopapular rash, fatigue or myalgia, and arthritis and arthralgia [6].
ZIKV was first isolated from the blood of a sentinel rhesus monkey from the Zika Forest in Uganda [7].
Serological studies and isolation of ZIKV strains have www.eurosurveillance.org Discussion and conclusion

Our two cases are among the first imported cases found linked to the recent outbreak in French Polynesia starting in 2013. They occur shortly after 26 imported cases into New Caledonia from the same outbreak, as well as the report of one indigenous case [10]. Aside from cases related to French Polynesia, imported Zika fever cases have been previously identified in travellers returning from Africa and south-east Asia. These include a case of sexually transmitted Zika fever following two imported cases from Senegal into the
United States, and an imported case of Zika fever from
Indonesia to Australia [11,12]. Two imported cases from
Thailand, one to Canada [13] and one to Germany [14] have also recently been reported.
Although the numbers of imported cases described so far are limited, the possibilities of ZIKV infections to be underdiagnosed and underreported are high due to generally mild symptoms and self-limited disease.
Additionally, due to the similarity of ZIKV disease symptoms to those of dengue and chikungunya, differential diagnosis is required to define the extent of
ZIKV epidemic. Importantly, as dengue virus (DENV) outbreaks also occur in French Polynesia [2], differential diagnosis between ZIKV infection and dengue is required in cases related to this area. Because of the ongoing dengue epidemic in Bora Bora, DENV infection was excluded in both cases in this study, by confirming that the serum samples were negative for both dengue virus nonstructural glycoprotein-1 (NS1) antigen and
IgM/IgG antibodies, using rapid diagnostic kits (SD
Bioline Dengue Duo Combo, Alere Medical, Inc.).
In this study, the two cases of ZIKV infection had not only leucopenia but also mild thrombocytopenia.
51

Figure 3
Phylogenetic analysis of a Zika virus sequence derived from a case of imported Zika virus infection from French Polynesia,
Japan, January 2014
ZIKV Hu/Tahiti/01u/2014NIID strain Japan-Tahiti2014
JN860885 ZIKV FSS13025 strain Cambodia2010
EU545988 ZIKV Micronesia 2007
HQ234499 ZIKV P6-740 strain Malaysia1966
HQ234500 ZIKV IbH30656 strain Nigeria1968
HQ234501 ZIKV ArD41519 strain Senegal1984
AY632535 ZIKV MR766 strain Uganda1947
Outgroup (DQ859064 Spondweni virus)

0.05
The phylogenetic tree was based on partial E-protein nucleotide sequences and compiled using the neighbour joining method (Genetyx,
Japan). The sequence of the Spondweni virus (GenBank accession number DQ859064) was used as an outgroup. Bootstrap percentages based on 1,000 replicates are shown on the tree nodes. The sequence of the case of imported Zika virus infection from French Polynesia to
Japan in January 2014 is indicated with an arrow. Scale bar (0.05) indicates nucleotide substitutions per site.

Previous investigators reported leucopenia, but not thrombocytopenia in patients with ZIKV infection [12].
Our two cases suggest that ZIKV infection can be associated with clinical features including thrombocytopenia and leucopenia, and shares similar clinical features to those of dengue fever and yellow fever.
In the second case identified in this study, viral RNA was negative in the serum sample but was positive in the urine sample. To our knowledge, this is the first case diagnosed by detection of Zika viral particles in urine. Detection of DENV genome in urine after disappearance of the viral genome in serum samples by realtime RT-PCR has been a useful laboratory diagnostic method [15]. Our case suggests that detection of Zika virus genome in urine by real-time RT-PCR is useful to confirm ZIKV infection, particularly after disappearance of viraemia in serum.
Phylogenetic analysis revealed that the ZIKV genome sequences of case 2, had a high sequence homology with recent strains from Asia and Micronesia, including those detected in Cambodia in 2010, but sequence homology was low with a strain isolated in 1947, the
Ugandan prototype MR766 strain [4].
The ongoing ZIKV outbreaks in French Polynesia and the confirmation of ZIKV viraemic travellers in our study suggests that in addition to enhanced and continued surveillance efforts, awareness among healthcare professionals should be raised that ZIKV infection ought to be considered as differential diagnosis in febrile patients with rash returning from areas affected by this virus. Further prevention measures, such as offering advice on the use of insect repellents during
52

travel to regions with outbreaks, would be important for ZIKV disease control.
Acknowledgments
This work was supported by funding from Research on
Emerging and Re-emerging Infectious Diseases by the
Ministry of Health, Labor and Welfare, Japan (H24-shinkouippan-013, H23-shinkou-ippan-010).

Conflict of interest
None declared.

Authors’ contributions
Satoshi Kutsuna collected the data and drafted the manuscript; Yasuyuki Kato participated in the coordination and concept of the manuscript and edited the manuscript and helped with the draft of the manuscript; Tomohiko Takasaki,
Meng Ling Moi, Akira Kotaki performed real-time RT-PCR and performed the phylogenetic analysis; Haruka Uemura,
Takashi Matono, Yoshihiro Fujiya, Momoko Mawatari, Nozomi
Takeshita, Kayoko Hayakawa collected the data and participated in the concept of the manuscript; Shuzo Kanagawa,
Norio Ohmagari revised the article for intellectual content.
All authors read and critically revised the first as well as the subsequent and final drafts of this manuscript.

* Addendum:
The GenBank accession number of the partial Zika virus nucleotide sequence derived from a sample obtained from case
2 was added on 07 February 2014.

www.eurosurveillance.org

* Erratum:
The title of this manuscript was initially wrong at the time of publication: ‘Two cases of Zika fever imported from French
Polynesia to Japan, December to January 2013’. The mistake was corrected on 31 January 2014.

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53

Rapid communications

First case of laboratory-confirmed Zika virus infection imported into Europe, November 2013
D Tappe1,2, J Rissland2,3, M Gabriel1, P Emmerich1, S Günther1, G Held4 , S Smola2,3, J Schmidt-Chanasit (jonassi@gmx.de)1,2,5
1. Bernhard Nocht Institute for Tropical Medicine, WHO Collaborating Centre for Arbovirus and Haemorrhagic Fever Reference and Research, Hamburg, Germany
2. These authors contributed equally to this work
3. Institute of Virology, Saarland University Medical Center, Homburg/Saar, Germany
4. Internal Medicine I, Saarland University Medical Center, Homburg/Saar, Germany
5. German Centre for Infection Research (DZIF), partner site Hamburg-Luebeck-Borstel, Hamburg, Germany
Citation style for this article:
Tappe D, Rissland J, Gabriel M, Emmerich P, Günther S, Held G, Smola S, Schmidt-Chanasit J. First case of laboratory-confirmed Zika virus infection imported into
Europe, November 2013. Euro Surveill. 2014;19(4):pii=20685. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20685
Article submitted on 27 January 2014 / published on 30 January 2014

In November 2013, an acute Zika virus (ZIKV) infection was diagnosed in a German traveller returning from Thailand. The patient reported a clinical picture resembling dengue fever. Serological investigations revealed anti-ZIKV-IgM and -IgG, as well as ZIKVspecific neutralising antibodies in the patient’s blood.
In Europe, viraemic travellers may become a source of local transmission of ZIKV, because Aedes albopictus
(Skuse) and Ae. aegypti (Linnaeus) are invasive mosquitoes and competent vectors for ZIKV.
We report the clinical and laboratory findings of a
Zika virus (ZIKV) infection imported into Europe by a
German traveller from Thailand, in winter of 2013.

C-reactive protein level (5.9 mg/L; normal value

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