Concurrent outbreaks of dengue , chikungunya and Zika virus infections – an unprecedented epidemic wave of mosquito-borne viruses in the Pacific 2012 – 2014

Since January 2012, the Pacific Region has experienced 28 new documented outbreaks and circulation of dengue, chikungunya and Zika virus. These mosquito-borne disease epidemics seem to become more frequent and diverse, and it is likely that this is only the early stages of a wave that will continue for several years. Improved surveillance and response measures are needed to mitigate the already heavy burden on island health systems and limit further spread to other parts of the world.

Since January 2012, the Pacific Region has experienced 28 new documented outbreaks and circulation of dengue, chikungunya and Zika virus. These mosquito-borne disease epidemics seem to become more frequent and diverse, and it is likely that this is only the early stages of a wave that will continue for several years. Improved surveillance and response measures are needed to mitigate the already heavy burden on island health systems and limit further spread to other parts of the world.
Since January 2012, the Pacific is experiencing a high burden of mosquito-borne disease due to concurrent epidemics of dengue, chikungunya and Zika virus infections. So far over 120,000 people have been reported to be affected, a figure that is likely to substantially underestimate the real numbers due to underreporting. For as long as there has been data available from the Region (i.e. 40 years), this epidemic wave of mosquitoborne viruses with 28 new mosquito-borne viral outbreaks (n=25) and circulation (n=3) documented since January 2012 (18 Dengue virus (DENV) serotype 1-4, 7 chikungunya virus and 3 Zika virus infection outbreaks, respectively) is unprecedented (Table) [1][2][3]. We here present an overview of the surveillance and epidemiology of these mosquito-borne disease epidemics in the Pacific Region, to help facilitate response measures that are needed to mitigate the already heavy burden on island health systems and to limit further spread to other parts of the world.

Surveillance of mosquito-borne viruses in the Pacific Region
The Pacific Public Health Surveillance Network (PPHSN) is a voluntary network of countries, territories and organisations created in 1996. It is dedicated to the promotion of public health surveillance and response to health emergencies in the Pacific Region. It covers 22 Pacific Island countries and territories (hereafter referred to as the Pacific Region) with a population of 10.6 million inhabitants [4]. The network services include the timely exchange of information on outbreak-prone disease through PacNet, an email list with around 680 health professionals, and diagnostic support through a network of laboratories for identification and verification of pathogens.
In 2010, the Pacific Syndromic Surveillance System was introduced in the PPHSN. It monitors four syndromes and aims at improved early warning to complement routine notifiable disease notification systems that generally are not timely and seldom used for regional surveillance purposes in the Pacific Region. The Syndromic Surveillance system is under development and currently includes sentinel reporting from primary healthcare or hospital sites in all countries [5]. Manifest dengue, chikungunya and Zika virus infections have a similar initial clinical presentation and may be reported as any of the first three of the following four monitored syndromes: (i) acute fever and rash, (ii) prolonged fever, (iii) influenza-like illness and (iv) diarrhoea. Due to similar initial clinical features to the three mosquito-borne diseases, concurrent measles epidemics and leptospirosis pose diagnostic challenges in the Region.
There is a need for timely, reliable and detailed data on mosquito-borne virus outbreaks and circulation of the viruses in the Pacific Region. To obtain a comprehensible overview of the present epidemiological picture, several sources of information are used. Further to PacNet, syndromic and laboratory-based surveillance, event-based surveillance (mainly media and personal communications with health professionals) and surveillance by-proxy (reports of exported cases to neighbouring countries) [6] are also important. To facilitate better risk assessments and efficiency of data dissemination, this data is visualized in a recently launched interactive map available from: www.spc.int/phd/epidemics. The map, updated weekly, provides the region for the first time with a dynamic real-time picture of the current epidemic situation.

The epidemiology of mosquito-borne viruses in the Pacific Region
Mosquito-borne virus diseases in the Pacific Region have a distinct epidemiology due to small populations scattered over thousands of tropical and sub-tropical islands on both sides of the equator in relative geographic isolation, together with (nowadays) significant people's mobility and thereby exposure to circulating arboviruses through the airline networks of the Asia-Pacific region (Figure 1). Between

Dengue
The epidemic pattern of dengue in the Pacific Region has typically presented in form of sporadic or rare epidemics rather than a hyperepidemic/endemic pattern, with one dominating serotype sweeping across the islands every 3 to 5 years, and with varying duration of circulation in different islands largely depending on population size [1,[7][8].  Numbers of cases reported decreasing or viral circulation is ongoing.
Outbreak reported to be over and/or no cases have been reported for one year.

Chikungunya
After being reported in the Pacific for the first time in a small tightly controlled outbreak in New Caledonia in 2011 [11], CHIKV is currently becoming established in the Region (Figure 1, Table) [2]. In Papua New-Guinea in 2012-13, the largest epidemic in the Region so far with estimated (though poorly documented) tens of thousands of cases, was caused by the East Central South African (ECSA) lineage of the virus [2]. The Asian lineage of the virus was responsible for the outbreak in Yap State (2013-14) [12] and also in New Caledonia (2013) where CHIKV re-emerged in the middle of a large DENV-1 epidemic and caused a small outbreak, similar to the 2011 outbreak (Table) [13]. Phylogenetic analyses of the CHIKV involved in the outbreaks in Tonga, Samoa and American Samoa are not yet available. Due to the on-going geographic expansion of Aedes albopictus in the Pacific region (Figure 3), virus genotype monitoring is a crucial aspect of surveillance.

Zika virus infections
After the first documented Pacific Zika outbreak in Yap in 2007 [14], the Asian lineage of the virus reappeared in French Polynesia in October 2013, and has since caused large outbreaks in New Caledonia (1,400 confirmed cases), Cook Islands (over 900 cases) and Easter Island that is not part of the PPHSN (Figure 1, Table) [3]. In French Polynesia, extrapolation of the 8,746 suspect cases reported by the sentinel surveillance network allows to infer that over 30,000 medical consultations were due to the spread of Zika virus throughout the archipelago. Between November 2013 and February 2014, increased incidence of neurological complications, including 42 cases of Guillain-Barré syndrome, was a unique and worrying feature of the French Polynesia outbreak that warrants further studies [3].

Burden on the Pacific countries and territories
Mosquito-borne outbreaks are greatly exacerbating the pre-existing burden that Pacific Island primary healthcare systems face. If not managed well, the epidemic wave may threaten societies broadly, affecting trade, tourism and work force beyond the direct morbidity and mortality toll [2]. During the chikungunya outbreak in Reunion Island, one third of the around 800,000 inhabitants were infected, peaking at more than 47,000 estimated cases in one week, with estimated productivity loss of €17.4 million (range €6 to €28.9 million) and medical costs of €43.9 million that were met by the French state [15][16][17]. Much of the burden on the Pacific Region of the concurrent epidemics of all three diseases covered here is unknown and further studies are warranted, especially on co-infection and the effect of sequential infection with different viruses.
Zika virus disease, generally reported to have a mild clinical presentation, was associated with neurological complications during concurrent Zika virus disease and dengue epidemics in French Polynesia [3,18]. The Pacific Region may be particularly vulnerable to communicable diseases due to isolation and immunologically naive populations, but also due to rates of non-communicable disease, such as obesity, diabetes and cardiovascular disease, that are among the world's highest on some islands [19].

The risk for further spread
While there have been efforts to improve surveillance in the Pacific over the past two decades, it is not likely that the extent of the current increase in diversity and frequency of mosquito-borne virus outbreaks in the Pacific can be explained solely by improved surveillance systems. In the island setting of the Indian Ocean, the largest documented CHIKV outbreak lasted four years (2004)(2005)(2006)(2007) [15]. Therefore, considering also the previous dengue outbreaks in the Pacific Region [1][2] and the diversity of the current outbreaks, it seems likely that the Pacific Region is in the early stages of an epidemic wave for the three mosquito-borne viruses that started in 2012 and is likely to continue for several years.
The risk for further spread in the Pacific Region is high for several reasons. Firstly, it is likely that there is little immunity to these diseases, as DENV-3 had not been  circulating in the Region since 1995 [1] and prior to the current wave, CHIKV and Zika virus occurrence in the Pacific was limited to two documented outbreaks [11,14]. Secondly, competent vectors present in the Region, mainly Ae. aegypti and Ae. albopictus, but also other local mosquitoes such as Ae. polynesiensis or Ae. hensilli are known to transmit these viruses (Figure 3) [20]. These species have been incriminated in DENV transmission on epidemiological and/or experimental (laboratory infections) grounds. Several of them are confirmed or strongly suspected vectors of CHIKV and Zika viruses [21]. Thirdly, large population mobility and airline travel facilitate the spread [22].
Vector control capacity in the Pacific Region is often limited or insufficient [11]. At present, there is no ongoing entomological surveillance system targeting vectors of dengue and other arboviruses established in the Region except in New Caledonia, Fiji and French Polynesia. The current knowledge about mosquito distribution in the other countries and territories is based on data collected during entomological investigations in surveys from the second half of the 20th century and from some more recent surveys [20]. Interestingly, the three viruses involved in this epidemic wave are not broadly mosquito-borne, but specifically Aedes (Stegomyia)-borne.
The cause of the recent increase in mosquito-borne disease in the Pacific Region is largely unknown, but is in line with a global increase of emerging diseases, and likely driven by a combination of socio-economic, environmental and ecological factors [23].
The continuous challenges of dengue and chikungunya [24] and more recently Zika virus infections [25]   for Europe, the re-emergence of dengue in Japan [26], and the first-time chikungunya transmission in the Americas [27], show that these viruses pose a threat to any country with competent vectors. The epidemiology of mosquito-borne viruses in the Pacific may be changing. There are close links between the several European overseas countries and territories in the Pacific Region and Europe and the United States [28]. Considering the extensive airline travel between the Pacific Region and other parts of the world where the viruses have not yet been established e.g. Europe and the United States, it should be of international interest to stay informed of the spread of the current Pacific Region wave of mosquito-borne viruses and to support surveillance and control efforts [2,23,29].
Examples of response from PPHSN partners to the epidemic situation include the provision of support and capacity building to Pacific Islands in surveillance, outbreak investigation and response, and mass-gathering surveillance. The Pacific Outbreak Manual is also being updated to include specific response guidelines for the three viruses [30].
To further enhance surveillance and response measures, Pacific Directors and Ministers of Health have shared the current risk assessment, and the upcoming Pacific International Health Regulations meeting will focus on mosquito-borne diseases. Island primary healthcare-based systems have difficulties to cope with high caseloads and there is a need for early multidisciplinary preparedness and response to face larger outbreaks adequately [2].