Increased risk of yellow fever infections among unvaccinated European travellers due to ongoing outbreak in Brazil, July 2017 to March 2018

Since December 2016, Brazil has faced a large outbreak of yellow fever with ca 1,500 confirmed human cases. In the first 2 months of 2018, Brazil reported almost as many cases as in 2017 as a whole. In these 2 months, five imported cases were reported among unvaccinated European travellers. Three had travelled to Ilha Grande, a popular destination among European tourists. Physicians and European travellers visiting Brazil should follow yellow fever vaccination recommendations.


Ongoing outbreak in Brazil
Yellow fever is an arboviral disease of primates transmitted by mosquitoes of the Aedes and Haemagog us species. In Brazil, YF is endemic in large parts of the country. Historically, the regions from where most cases were reported were forested and rural areas such the hydrographic basins of the Amazon, Araguaia, Tocantins and Paraná rivers [2].
In 2014/15, YF virus emerged at the periphery of endemic areas with the detection of non-human primate (NHP) cases [1]. In Brazil, yellow fever surveillance is set up from July to June the following year. During the surveillance period 2016/17 (July 2016 to June 2017), the virus spread geographically, reaching nine states in central and south-eastern Brazil (i.e. Distrito Federal, Espírito Santo, Goiás, Mato Grosso, Minas Gerais, Pará, Rio de Janeiro, São Paulo and Tocantins) and causing 779 human cases including 262 deaths ( Figure 1) [1].
In addition, 1,659 epizootics (clusters of cases detected among NHPs) in NHPs were reported, causing the death of more than 2,000 animals. After a decline in incidence of human cases from April to May 2017, and very few cases reported between June and November 2017, a second wave of the outbreak started in December 2017 ( Figure 2) [3].
From July 2017 to 13 March 2018, 920 confirmed human cases including 300 deaths were reported; most cases occurred in January and February 2018 [3]. In comparison, during the same period in 2016/17, there were ca 610 confirmed human cases. Between July 2017 and 13 March 2018, five states reported YF cases: Minas Gerais (n = 415), São Paulo (n = 376), Rio de Janeiro (n = 123), Espírito Santo (n = 5) and Distrito Federal (n = 1). In the same period, there were 617 epizootics, the majority of them in the State of São Paulo (n = 502) ( Figure 3). While the increase in the number of human cases started in December 2017, the upsurge of epizootics has been ongoing since mid-September 2017. This situation is consistent with the fact that NHPs are more exposed to mosquitoes compared with humans, hence they are commonly used as sentinels for early detection of YF transmission [2,4].
The detection of epizootic events in the States of São Paulo and Rio de Janeiro with close vicinity to two highly populated metropolitan regions remains of concern [5,6]. It highlights an increased likelihood of peri-urban or urban cycles of YF transmission, which in megacities such as São Paulo and Rio de Janeiro could lead to very large outbreaks and consequently higher risk of exposure of international travellers.  On 15 February 2018, YF virus was identified in Ae. albopictus mosquitoes captured in two municipalities (Ituêta and Alvarenga) in Minas Gerais state [7]. In a laboratory setting, studied Brazilian populations of Ae. albopictus have proven to be a competent vector for YF virus which underlines the risk of potential spread of the virus through this mosquito species and hypothetically the risk of sustained urban cycle through Ae. albopictus [8].
Brazil is currently conducting mass vaccination campaigns to increase the vaccination coverage in Bahia, Rio de Janeiro and São Paulo states. As at 13 March 2018, 17.5 million people have been vaccinated, with vaccination coverages of 54%, 69% and 95% in the three states respectively [3].

Travellers and imported cases
According to the International Air Transport Association, between 2012 and 2016, there were on States with confirmed locally-acquired cases since July 2017 The Carnival, one of the largest international mass gatherings in Brazil, took place between 9 and 14 February 2018. This event brings together several millions of people from throughout the country and from abroad. In its rapid risk assessment published on 18 January 2018, the European Centre for Disease Prevention and Control (ECDC) highlighted the possibility of an increase in number of travel-related cases among unvaccinated Europeans [10]. Since January 2018, five unvaccinated European travellers were infected in Brazil (Table).

Imported cases within South America
Six travel-related cases among non-European travellers were reported in February 2018, three by Argentina and three by Chile. For five cases age was available, they were between 20 and 45 years old, the majority were men (n = 4), all five for whom information was available were unvaccinated, two cases died. Five of the six cases reported a travel to Ilha Grande, Angra dos Reis municipality [12,13].

Discussion and conclusions
The increase in YF transmission in central and southeastern Brazil has resulted in the occurrence of travelrelated cases among unvaccinated European and South American travellers who visited popular tourist destinations where the virus is circulating intensely. The recent change in the YF epidemiological situation in Brazil seems to be particularly noticeable in Ilha Grande a common travel destination and the place of exposure of the majority of the travel-related cases.
The YF cases in non-vaccinated tourists highlight the relevance of YF vaccination of travellers to risk areas for YF and the need for a comprehensive pre-travel advice to assess the vaccination status. These cases also emphasize that the epidemiological situation in each region is or may be evolving rapidly and that pre-travel advice should be completed in a timeframe allowing to consider the latest epidemiological situation while providing enough time for an efficient vaccination protection.

Risk of spread of yellow fever virus in Europe
The probability of local YF transmission in continental Europe following introduction of the virus by a viraemic traveller is currently considered very low; Ae. aegypti, the main vector of YF virus in urban settings, is absent in continental Europe. It is established in the outermost region of Madeira and was recently introduced in the Canary Islands [14]. During the European winter season the weather conditions are, however, not favourable to vector activity. Ae. albopictus, which is largely established in the southern part of continental Europe, was shown to be a competent vector for YF virus in laboratory settings, though YF transmission via Ae. albopictus has never been observed in nature [14,15].

Public health implications for Europe
To inform European public health authorities about the YF risk for travellers, ECDC has published several risk assessments [10]. Through the VectorNet project, ECDC is monitoring the presence/absence of Ae. aegypti and Ae. albopictus in Europe [14].
The two consecutive waves of transmission, both of a previously undocumented magnitude, have caused the World Health Organization and the Brazilian health authorities to review the areas considered at risk in Brazil. European health practitioners should remain attentive to the evolution of the epidemic and related updates in areas at risk and ensure adequate vaccination of their patients.
The last urban YF outbreak in Brazil took place in 1942 in Acre [16]; since then the risk of an urban cycle becoming established in cities such as São Paulo and Rio de Janeiro has never been as high as at present. The live-attenuated virus YF vaccine is safe, effective, and inexpensive and provides life-long immunity. The vaccine thus remains the most important means of preventing infections and controlling YF outbreaks [17]. ECDC encourages European countries to strengthen their awareness campaigns for travellers to Brazil to ensure that they are vaccinated if travelling to at-risk areas, in accordance with respective national recommendations ( Figure 3) [18]. Travellers with contraindication for vaccination should seek medical advice before departure. In addition, it is important that clinicians are alerted to the ongoing outbreak and are able to early diagnose YF in travellers with compatible clinical symptoms. Finally, to protect themselves from YF infection and other arboviral diseases occurring in Brazil (e.g. dengue), travellers should avoid mosquito bites using chemical and/or mechanical barriers such as mosquito repellent, long-sleeved tee shirts and long trousers and bed nets.