Diagnosis made on clinical grounds can be difficult as physical symptoms as well as endemic areas with dengue and chikungunya virus overlap and is therefore unreliable. In case of mild infection, which is in the majority of cases, there is generally no need for PCR/serological testing and as a consequence high infection rates are usually found by active surveillance.

Principally vector source control measures are taken by governments to control the ZIKV epidemic, as no treatment or vaccines are available to date. Measures include removing mosquito breeding grounds and the use of insect sprays. Education of the public[32] and travel advice for pregnant woman as well as women and men wanting to have a child (as ZIKV can harbour in semen) to restrict travel to endemic areas and to prevent vertical transmission, are cornerstones of prevention strategies of various governments and health organisations.

Pandemic potential of Zika virus
Irrespective of the biological class of a pathogen, several attributes are likely to be essential components of the pandemic threat potential of pathogens. These traits include efficient human-to-human transmissibility, an appreciable case fatality rate, the absence of an effective or widely available medical countermeasure, an immunologically naïve population, virulence factors enabling immune system evasion and respiratory mode of spread. Additionally, the ability to transmit during incubation
periods and/or the occurrence of mild illnesses would further augment spread. Zika is mainly transmitted to humans through mosquitoes and human-to-human transmission is rare. Case fatality rate is low and there is no respiratory spread. Taken together, the severity of pandemic potential could be classified as low. However, the uniquely dangerous trait of ZIKV that it can circulate unnoticed for years among populations and infection of populations without previous acquired immunity against ZIKV provides a substantial risk for large outbreaks.[33] Subsequently, it causes large-scale negative reproductive effects, represented by foetal complications, which only become manifest months after introduction of the virus.[33]

Invasion of a new (immune naive) population was probably an important factor in the explosive emergence of ZIKV in Brazil, as the decline in Zika cases was particularly attributed to the rise in immunity with a peak seroprevalence of 63% in 2016.[33] As associated congenital complications were not reported previously in endemic areas, the number of associated cases in Brazil was unexpected. It is likely that ZIKV infection at a young age protects pregnant women against foetal complications later on and that foetal complications mainly occur in primo infections[34] such as in Brazil. Besides immune naivety, ZIKV infection was associated with higher population density, the incidence of dengue, Aedes larvae infestation index and average rainfall.[35] Other issues that potentially influenced this outbreak, including evolution of the virus and potential domestic and wild animal reservoirs, remain largely unresolved to date.

Mosquitoes from the Aedes genus were originally found in tropical and subtropical areas but they are gradually spreading, including to the south of Europe and the United States following climate change.[36] In particular, the distribution area of the mosquito species Aedes albopictus has been increasing over the years and several models predict that 83% of urban areas in Europe will become suitable over time.[37] Aedes albopictus has been shown to be a competent vector of ZIKV[38] and other viruses including dengue and chikungunya. Besides Europe, numerous other immunologically naive populations have been identified as high-risk countries, including those with limited medical resources and (pre) pregnancy surveillance.[39]

In 2016, the first autochthonous ZIKV disease cases acquired via vector-borne transmission in Europe were reported in France. In this cluster, three persons became infected in a short period of time and no travel history to any of the Zika endemic areas was present. These cases reinforce the hypothesis that autochthonous vector-borne transmission of ZIKV in nonendemic areas is possible and could be aided by Aedes albopictus or other mosquito species that have yet to be determined.

Introduction of the virus by travellers from endemic areas has been described[10,40] and could potentially be the source of circulating ZIKV in new mosquito populations in non-endemic areas, as mosquito-to-mosquito infection has not been reported. The role of human-to-human infection has to be investigated, but several studies showed long-standing viral loads in body fluids including semen, in some cases leading to late humanto human transmission.[21] Compared with other flaviviruses, sexual transmission and persistence in the genitourinary tract seem to be unique.

During outbreaks, humans act a reservoir, but it is proposed that especially monkeys are a natural reservoir in endemic areas, as the virus was isolated from several species and experimental inoculation caused viraemia and seroconversion.[41] However, antibodies have also been detected in domestic sheep, goats, horses, cows, ducks, rodents, bats, orangutans and carabaos[1] and in a surveillance study from Brazil in 2018 ZIKV was detected in numerous other vertebrates.[42] The role of possible reservoirs in currently non-endemic areas has not been established and detection of ZIKV in animals does not necessarily imply that animal-to-mosquito-to human infection takes place, as this also depends on other characteristics of the host, the vector and the virus itself. Still, if for instance domestic animals emerge to be suitable as a reservoir, it could potentially enhance further spread and maintain circulation of ZIKV in the absence of current known reservoirs, including monkeys.

Conclusion
ZIKV is a vector-borne virus that generally causes no or mild clinical symptoms. However, the uniquely dangerous aspect of ZIKV infection is that maternal infection is associated with serious congenital disorders. From 2007, increasing numbers of cases of ZIKV are being described and in 2015 a large outbreak was reported in Brazil followed by a substantial number of newborns with microcephaly several months later. The spread of mosquitoes from the Aedes genus to areas such as the US and Europe will significantly increase the potential of upcoming Zika infections in these regions in the near future.

Disclosures
All authors declare no conflict of interest. No funding or financial support was received.